Professional Documents
Culture Documents
Congenital
Heart Diseases
http://vip.persianss.ir
A Comprehensive Approach to
Congenital
Heart Diseases
Editor-in-Chief
IB Vijayalakshmi
MD, DM, FICC, FIAMS, FIAE, FCSI, FICP, FAMS, DSc
Editors
P Syamasundar Rao
MD, DCH, FAAP, FACC, FSCAI
Professor of Pediatrics and Medicine
Emeritus Chief of Pediatric Cardiology
UT-Houston Medical School
Houston, Texas, USA
Reema Chugh
MD, FACC
Consultant
Cardiology/Adult Congenital Heart Disease
and Heart Disease in Pregnancy
Kaiser Permanente Medical Center
Panorama City, California, USA
® Foreword
Dr Joseph K Perloff
Headquarter
Jaypee Brothers Medical Publishers (P) Ltd
4838/24, Ansari Road, Daryaganj
New Delhi 110 002, India
Phone: +91-11-43574357
Fax: +91-11-43574314
Email: jaypee@jaypeebrothers.com
Overseas Offices
J.P. Medical Ltd. Jaypee-Highlights medical publishers Inc.
83 Victoria Street, London City of Knowledge, Bld. 237, Clayton
SW1H 0HW (UK) Panama City, Panama
Phone: +44-2031708910 Phone: + 507-301-0496
Fax: +02-03-0086180 Fax: + 507-301-0499
Email: info@jpmedpub.com Email: cservice@jphmedical.com
Jaypee Brothers Medical Publishers Ltd Jaypee Brothers Medical Publishers (P) Ltd
The Bourse 17/1-B Babar Road, Block-B, Shaymali
111 South Independence Mall East Mohammadpur, Dhaka-1207
Suite 835, Philadelphia, PA 19106, USA Bangladesh
Phone: + 267-519-9789 Mobile: +08801912003485
Email: joe.rusko@jaypeebrothers.com Email: jaypeedhaka@gmail.com
Website: www.jaypeebrothers.com
Website: www.jaypeedigital.com
All rights reserved. No part of this book may be reproduced in any form or by any means without the prior permission of the
publisher.
This book has been published in good faith that the contents provided by the contributors contained herein are original, and is
intended for educational purposes only. While every effort is made to ensure accuracy of information, the publisher and the editor
specifically disclaim any damage, liability, or loss incurred, directly or indirectly, from the use or application of any of the contents
of this work. If not specifically stated, all figures and tables are courtesy of the editor.
ISBN 978-93-5090-267-7
Printed at
Dedicated to
Maude Abbott
First to publish An Atlas of Congenital Heart Disease
Madam Helen Taussig
Mother of Pediatric Cardiology
Dr Joseph K Perloff
Master teacher of Congenital Heart Diseases
Dr S Padmavati
A doyenne of Pediatric Cardiology in India
who has inspired many like me to become Cardiologists
—Dr IB Vijayalakshmi
My teachers
Dr Lavanya Muhkerjee, Dr Herman W Lipow, Dr Norman J Sissman
Dr Jerome Liebman, Dr Leonard M Linde
My parents
Dr PVB Krishna Rao, Dr Patnana Savithramma
My wife and children
Dr Hymavathi
Dr Vijay Kumar, Dr Madhavi, Dr Radhika
Above all
To all the patients
Past, present and future
Who are our best teachers
and
For whom the quest for knowledge continues...
http://vip.persianss.ir
Contributors
Abhilash SP MD DM James R Bentham DPhil BM BCh BA Charles W Hoopes
Assistant Professor of Cardiology Paediatric Cardiology Intervention Fellow Associate Professor of Surgery
Sree Chitra Tirunal Institute for Medical Yorkshire Heart Centre Director, Heart Lung Transplant and
Sciences and Technology Leeds General Infirmary Mechanical Cardiac Support Program
Trivandrum, Kerala, India Leeds, UK University of Kentucky College
abhispin@gmail.com bentham@well.ox.ac.uk of Medicine, Lexington, KY, USA
Bhanu Duggal MD DM Chitra Narasimhan MD FICPC
AM Jagadeesh MD Associate Professor of Cardiology
Professor and HOD Assistant Professor of Clinical
Grant Medical College and Pediatric Cardiology
of Cardiac Anesthesia Sir JJ group of Hospitals Sri Jayadeva Institute of Cardiovascular
Sri Jayadeva Institute of Cardiovascular Mumbai, India Sciences and Research
Sciences and Research medhawini2k@yahoo.com Bengaluru, India
Bengaluru, India
Bhushan Chavan chitradr@gmail.com
Anil Sivadasan Radha Junior Consultant in Pediatric Cardiology
Debasree Ganguly MD FNB(Ped Card)
MD DNB(Pediatrics) DNB(Cardiology)
Madras Medical Mission
Junior Consultant in Pediatric Cardiology
Consultant Pediatric Cardiologist Chennai, India
Rabindranath Tagore International Institute
Department of Pediatric Cardiac Sciences Biswajit Bandyopadhyay of Cardiac Sciences
Apollo Health City, Jubilee Hills Head of the Department Kolkata, India
Hyderabad, India Sr Consultant Pediatric Cardiologist debasreeganguly23@gmail.com
dranil.s.r@gmail.com Rabindranath Tagore International Institute
of Cardiac Sciences (RTIICS) Deborah J Kozik
Anita Shet MD Kolkata, India Assistant Professor of Surgery
Associate Professor bisban@rediffmail.com University of Kentucky College
Department of Pediatrics of Medicine
Brannon Hyde Pediatric Cardiac Surgery
St John’s Medical College Hospital
Fellow in Cardiothoracic Surgery Kentucky Children’s Hospital
Bengaluru, India
University of Kentucky Lexington, KY, USA
anitashet@gmail.com
College of Medicine
Lexington, KY, USA Devananda NS MS MCh
Anurakti Srivastava
Consultant and Head
MD(Pediatrics), Fellow (Pediatric Cardiology) Biswaranjan Mishra MD DM
Department of Cardiothoracic Surgery
Consultant Pediatric Cardiologist Chief Consultant Cardiologist
Manipal Heart Institute
Department of Pediatric Cardiac Sciences Eko Imaging Institute
Bengaluru, India
Apollo Health City, Jubilee Hills Medical Road, Mangalabag
devananda_ns@yahoo.com
Hyderabad, India Cuttack, Odisha, India
anurakti07@yahoo.co.in drbisumishra@yahoo.co.in Dinesh Choudhary
Chandrakant B Patil MD DM Fellow in Cardiac Electrophysiology
Arjun Kalyanpur ABR Professor and HOD of Cardiology Sree Chitra Tirunal Institute for Medical
Chief Radiologist St Johns Medical College Sciences and Technology
Teleradiology Solutions Bangaluru, India Trivandrum, India
Bengaluru, India drcbpatil@gmail.com drdineshchoudhary8@gmail.com
arjun.kalyanpur@telradsol.com
Chandrika YR MD Duraisamy Balaguru
Professor and HOD MBBS DCH MRCP (UK) FAAP FACC
Asha Moorthy MD DM
Pediatric Anesthesiology Associate Professor of Pediatrics
Professor of Cardiology
Indira Gandhi Institute of Division of Pediatric Cardiology
Sri Ramachandra University
Child Health UT-Houston Medical School
Chennai, India
Bengaluru, India Houston, Texas, USA
drashasrmc@yahoo.co.in
doctoryrc@gmail.com Duraisamy.Balaguru@uth.tmc.edu
http://vip.persianss.ir
English C Flack MD MS Kiron Varghese MD DM Mazeni Alwi
Clinical Fellow Professor of Cardiology Senior Consultant in Paediatric
Pediatric Heart Institute St Johns Medical College Cardiology Paediatric and
A Comprehensive Approach to Congenital Heart Diseases
Contributors
Sree Chitra Tirunal Institute for Medical Ahmanson/UCLA Metro Heart Institute
Sciences and Technology Adult Congenital Heart Disease Center Noida, NCR
Trivandrum, India University of California Los Angeles Ex-Director
kknnamboodiri@yahoo.co.in (UCLA) Professor and Head
Los Angeles, California, USA Cardiology Department
Narendra Babu M MS MCh
Maulana Azad Medical College and
Associate Professor of Pediatrc Surgery
PM Chandrasekhara MD FICC FIACTA GB Pant Hospital, New Delhi, India
Indira Gandhi Institute of Child Health
Professor and HOD yuktiarora@hotmail.com
Bengaluru, India
Anaesthesia and Pain Management
drnarendrababum88@gmail.com Ramesh Santhanakrishnan MS MCh DNB
Sagar Hospitals, Bengaluru, India
Neeraj Awasthy MD FNB pmc.cardiacanaes@gmail.com Professor and HOD of Pediatric Surgery
Associate Consultant Indira Gandhi Institute of Child Health
Department of Pediatric and Congenital Prabhat Kumar MD FSCAI Bengaluru, India
Escorts Heart Institute and Research Centre Professor and HOD of Pediatric Cardiology doctorsramesh@gmail.com
New Delhi, India Military Hospital (CTC)
Reema Chugh MD FACC
n_awasthy@yahoo.com Armed Forces Medical College
Consultant
Pune, India
Neeraj Raghani MD DM Cardiology/Adult Congenital Heart Disease
drprabhat_cardio@yahoo.co.in
Assistant Professor of Cardiology and Heart Disease in Pregnancy
Grant Medical College and Kaiser Permanente Medical Center
Sir JJ group of Hospitals Pradeep Vaideeswar Panorama City, California, USA
Mumbai, India Professor (Additional)
drnirajraghani@yahoo.co.in Department of Pathology R Suresh Kumar MD DM FSCAI
(Cardiovascular and Thoracic Division) Senior Consultant in Pediatric Cardiology
Neeru Kaushik MD Seth GS Medical College, Frontier Lifeline, Chennai and
Assistant Professor of Pediatrics Mumbai, India Dr KM Cherian Heart Foundation
Pediatric Heart Institute shreeprajai@yahoo.co.in Tiruvalla, India
Monroe Carell Jr Children’s Hospital r.sureshkumar.mmm@gmail.com
at Vanderbilt Prasanna Nyayadhish
Nashville, Tennessee, USA Professor of Cardiology Sanjay Khatri MD DNB(Ped) FDNB(Ped Card)
Seth GS Medical College and KEM Consultant
Nicholas Hayes MBChB MRCPCH
Hospital, Parel, Mumbai, India Department of Pediatric Cardiology
Locum Consultant in Paediatric Cardiology
prasannanyayadhish@hotmail.com Fortis-Escorts Heart Institute
Evelina Children’s Hospital
New Delhi, India
6th Floor, Westminster Bridge Road
London SE1 7EH, UK Prasanna Simha Mohan Rao MS MCh
Professor of CTVS Sanjeev Kumar Veeredddy
Nick.Hayes@gstt.nhs.uk Senior Resident in Cardiology
Sri Jayadeva Institute of Cardiovascular
Nirav Panchani MD DM Sciences and Research Seth GS Medical College
Assistant Professor of Cardiology Bengaluru, India and KEM Hospital
Grant Medical College and prasannasimha@gmail.com Parel, Mumbai, India
Sir JJ group of Hospitals dr_rahulreddy@yahoo.co.in
Mumbai, India Praveen Jayan JP MD DM
drniravpanchani@yahoo.com Satish MD DM
Consultant Cardiologist Assistant Professor of Cardiology
Nolan Thompson MD Bharath Hospital Sri Jayadeva Institute of Cardiovascular
Chief of Service Kottayam, Kerala, India Sciences and Research
Department of Psychiatry praveenjayan@gmail.com Bengaluru, India
Kaiser Permanente Medical Center reddy7sathish7@yahoo.com
Panorama City, California, USA P Syamasundar Rao
MD DCH FAAP FACC FSCAI Satish Govindiah MS MCh
Sudhayakumar N MD DM Professor of Pediatrics and Medicine Professor of CTVS
Professor of Cardiology Emeritus Chief of Pediatric Cardiology Sri Jayadeva Institute of Cardiovascular
Amrita Institute of Medical Sciences UT-Houston Medical School Sciences and Research
Kerala, India Houston, Texas, USA Bengaluru, India
nsudhayakumar@gmail.com P.Syamasundar.Rao@uth.tmc.edu satishgovindaiah@yahoo.co.in
ix
http://vip.persianss.ir
Seema Thakur S Radhakrishnan MD DM Syed T Rizvi MD
Senior Consultant HOD and Director Consultant in Psychiatry
Genetic and Fetal Medicine Department of Pediatric and Congenital Child and Adolescent Psychiatry
A Comprehensive Approach to Congenital Heart Diseases
Fortis Health Care, New Delhi, India Escorts Heart Institute and Research Centre Department of Psychiatry
New Delhi, India Kaiser Permanente Medical Center
Sejal Shah
samurai43@yahoo.com Panorama City, California, USA
Consultant
Pediatric Cardiology Thomas P Graham MD
Sridevi Hegde MBBS DCH PhD
Narayana Hrudayalaya Institute of Emeritus, Professor of Pediatrics
Head of Department and Consultant
Cardiac Sciences, Bengaluru, India Pediatric Heart Institute
Medical Genetics, Manipal Hospital
sejalshahsuresh@yahoo.com Monroe Carell Jr Children’s Hospital
Old Airport Road, Bengaluru, India
at Vanderbilt
Shada J Al-anani sridevi.hegde@manipalhospitals.com
Nashville, Tennessee, USA
Fellow in Pediatric Cardiology
Rush Center for Congenital and Srilatha Alapati MD Tracy Kustwan Livecchi
Structural Heart Disease Assistant Professor of Pediatrics Licensed Clinical Social Worker
Rush University Medical Center Division of Pediatric Cardiology Psychotherapist
Chicago, IL, USA Texas Tech Health Sciences Center Adult Congenital Heart Association
Amarillo, Texas, USA Mental Health Consultant
Shakeel Ahmed Qureshi
Westport, Connecticut, USA
Professor of Pediatric Cardiology
Evelina Children’s Hospital Shishu Shankar Mishra Varsha Kaulgud Mokhasi MD
6th Floor, Westminster Bridge Road MD FAIMS MCAM DoCM FCCP FIAE FICC Professor and HOD
London SE1 7EH, UK Professor and Director Department of Anatomy
Shakeel.Qureshi@gstt.nhs.uk Department of Cardiology Vydehi Institute of Medical Sciences
Hi-Tech Medical College Bhubaneswar Bengaluru, India
Shardha Srinivasan MD Sr Consultant Cardiologist varsha_mokhasi@yahoo.com
Associate Professor of Pediatrics Med ‘N’ Heart Clinic
Director of Fetal Cardiology Cuttack, Odisha, India Vimala J MD DM
Co-director of Echocardiography drssmishra@yahoo.com Senior Consultant Pediatric Cardiologist
American Family Children’s Hospital The Madras Medical Mission
University of Wisconsin, Madison, USA Sunita Maheshwari ABP ABPC(USA) Chennai, India
ssrinivasan3@pediatrics.wisc.edu Senior Consultant vimalajesudian@gmail.com
Pediatric Cardiologist Neil Wilson MB BS DCH FRCP FRCP(CH) FSCAI
Shilpa Suresh Mavanoor DNB MCh
Bengaluru, India Consultant Paediatric Cardiologist
Assistant Professor of CTVS
sunita.maheshwari@telradsol.com John Radcliffe and Children’s
Sri Jayadeva Institute of Cardiovascular
Sciences and Research Hospital Oxford
Bengaluru, India Suresh G Rao MS MCh Dip.NB FIACS Honorary Senior Lecturer Dept Paediatrics
shilpa.suresh@gmail.com Pediatric and Congenital Heart Surgeon University of Oxford
Director, Children’s Heart Centre Oxford, UK
Smita Mishra Kokilaben Dhirubhai Ambani Hospital neilwil1@aol.com
Senior Consultant Mumbai, India
Pediatric Cardiology raosureshg@gmail.com Ziyad M Hijazi MD MPH FSCAI FACC FAAP
Escorts-Fortis Health Care James A Hunter, University Chair
New Delhi, India Swati Garekar Professor of Pediatrics
smi1@rediffmail.com American Board Certified and Internal Medicine
(Pediatric Cardiology) Director, Rush Center for Congenital
Spoorthi Anup Belludi BDS MDS Consultant Pediatric Cardiologist and Structural Heart Disease
Professor of Periodontics Children’s Heart Centre Section Chief, Pediatric Cardiology
Department of Periodontics Kokilaben Dhirubhai Ambani Hospital Rush University Medical Center
KLE Society’s Institute of Dental Sciences Mumbai, India Chicago, IL, USA
Bengaluru, India swatigar@gmail.com Ziyad_Hijazi@rush.edu
x
Foreword
This thousand plus page book is a remarkable achievement that addresses the
seemingly impossible task of the spectrum of congenital heart disease from the
third week of intrauterine life to late end-of-life issues. Three exceptional Editors
were chosen to achieve this goal—IB Vijayalakshmi, P Syamasundar Rao, and
Reema Chugh. Together, they represent three generations who have witnessed
the major advances since the first blue baby operation at the Johns Hopkins
Hospital in 1944.
Survival into adulthood and the issues confronting adults with congenital
heart disease have added yet another dimension with Congenital Heart Disease in
Adults now a subspecialty in its own right. In the United States, there are currently
more adults with congenital heart disease than there are infants and children.
An attractive feature of the book is the seamless continuity from embryo, to neonate, child, adolescent, and adult.
Thirteen Sections are written by separate author(s), but the text reads as single-authored.
The first major facility in the English-speaking world dedicated to treating the young was the Hospital for Sick Children
in London established in 1852 with the aid of Charles Dickens. The second major facility was the Children’s Hospital of
Philadelphia founded three years later. The Children’s Hospital of Boston opened in 1869. Until the turn of the 20th century,
however, these institutions were little more than dim lights of hope in the darkness of pediatric medicine.
Where was congenital heart disease? Osler’s Principles and Practice of Medicine devoted a scanty five pages to Congenital
Affections of the Heart. Holt’s Diseases of Infancy and Childhood devoted seven pages to Congenital Anomalies of the Heart.
In 1929, in Eberswalde near Berlin, Werner Forssman performed the world’s first cardiac catheterization on himself. The
department chief warned him not to do it, but Forssman ignored him. A nurse tried to stop him, but he tied her to the
operating table to keep her out of the way. Into his own antecubital vein, Forssman introduced a cannula through which
he passed a 65 cm urethral catheter, and then walked up a flight of stairs to the X-ray department where a photograph
showed the catheter tip in his right atrium. The image revolutionized cardiology. Despite later joining the Nazi party, Nobel
Laureate Forssman died on June 1, 1979.
In 1896, two Viennese scientists, Edward Haschek and TO Lindenthal, injected liquid calcium carbonate into the hand
vessels of a cadaver, producing an image of the vascular system. In the 1930s, George Robb and Israel Steinberg at Bellevue
Hospital in New York developed angiography and perfected angiography as a practical technique. Iodine-based contrast
materials were injected into the blood vessels of rabbits, and in 1937, into human beings. Castellanos, Pereiras, and Garcia
in Havana, visualized the right cardiac chambers in infants and children. The internal structure of the living heart had been
revealed for the first time…
In 1956, Cournand, Dickinson and Forssman were awarded the Nobel Prize in Physiology or Medicine for their discoveries
concerning heart catheterization and pathological changes in the circulatory system.
Each of the thirteen Sections of the book is subdivided into beautifully illustrated chapters—Section 1 Embryo to the
Neonate, Section 2 Basics, Section 3 Defects in Atrioventricular Connections, Section 4 Shunt Defects, Section 5 Right
and Left Ventricular Obstructive Lesions, Section 6 Congenital Valvar Lesions, Section 7 Diseases of the Aorta, Section 8
Cyanotic Heart Disease, Section 9 Congenital Cardiomyopathies, Section 10 Congenital Heart Disease in Adults, Section 11
Electrophysiological Issues in Children, Section 12 Miscellaneous, and Section 13 General Issues.
A Comprehensive Approach to Congenital Heart Diseases by IB Vijayalakshmi, P Syamasundar Rao, and Reema Chugh deals
with congenital heart disease from intrauterine life to late end-of-life issues. The book is a tribute to the authors and a rare
gift to the reader.
Joseph K Perloff MD
Streisand/American Heart Association
Professor of Medicine and Pediatrics Emeritus
Ahmanson/UCLA Adult Congenital Heart Disease Center
University of California –Los Angeles School of Medicine
Los Angeles, California, USA
http://vip.persianss.ir
Prologue
I began my formal training in adult cardiology and pediatric cardiology,
after completing postgraduate studies in the UK, under the great and
foremost pediatric cardiologist, Dr Helen Taussig at the Harriet Lane
Home, Johns Hopkins Hospital, Baltimore, USA. There could not have
been a more exciting time for the specialty. Dr Robert Gross had ligated
a patent ductus arteriosus (PDA) and the first Blalock-Taussig (BT) shunt
had been performed by Dr Alfred Blalock at Hopkins a few years later. The
clinic at Harriet Lane was full of patients from all over the world. It was
one of the best periods of my life.
Since my return to India, I have been dealing mostly with adult
cardiology, a large pediatric component of rheumatic heart disease,
and with congenital heart disease (CHD) in both children and adults.
Looking back over a half century, the developments in this field are
breathtaking. At the Johns Hopkins Hospital, in the fifties we depended
on auscultation, the electrocardiogram (ECG), X-ray, fluoroscopy (a very
large slice) and cardiac catheterization for diagnosis even in small infants.
Surgery was at that time limited to closed procedures for CHD (BT or
aorto-pulmonary shunts, PDA ligation, coarctation of aorta repair, etc.).
Today, the advent of echocardiography has done away (almost totally)
with cardiac catheterization in babies. Catheter-based interventions for valve stenosis, device closure of atrial/ventricular
septal defects (ASD/VSD) and PDA along with new surgical procedures using the heart-lung machine have revolutionized
both diagnosis and treatment. Fetal echocardiography is helpful in the diagnosis of several malformations and is rapidly
developing. Correction of some CHDs in the fetal stage has begun in a few places around the world. Genetic and molecular
studies are developing in a big way.
The specialty of Pediatric Cardiology is a recognized entity today. However, there is still some pessimism about the
advances. For example, despite surgery, many patients with ASD, VSD develop cardiac arrhythmias later in life. Corrected
tetralogy of Fallot, transposition of the great arteries and coarctation of aorta almost always require reoperations.
I am sure that this book on congenital heart diseases will be useful for physicians, cardiologists, cardiac surgeons and
all students. It will hopefully help in establishing the exact cardiac burden and cost-effective methods for excellence in
pediatric heart care. Dr IB Vijayalaksmi, the co-editors and all the authors need to be congratulated for this venture.
http://vip.persianss.ir
Preface
Congenital heart diseases are the most common birth defects among neonates born worldwide. Advancements in
pediatrics, congenital heart surgery, anesthesia, internal medicine and obstetric/gynecology have allowed the majority
of these infants to survive from childhood into adulthood. Systematic categorization and classifications by embryologists/
pathologists had led to a fundamental understanding of these defects and their associated disorders.
It is, therefore, not surprising that most health providers including the specialists in this field are often overwhelmed
by the various congenital heart defects (CHD). For a clinician to understand the entire spectrum of CHD from embryology/
pathology, clinical manifestations, diagnostics tests, management and surgical indications for CHD appears to be an
insurmountable task. From making the correct diagnosis to appropriate management requires considerable knowledge
and experience. In addition, rapid advances in both catheter-based interventions and surgeries for fetus to grown-up/
adult congenital heart diseases (GUCH/ACHD) needs a deeper understanding of the guidelines and appropriate use criteria
(AUC) in order to facilitate proper decision-making by combining the best available scientific evidence with the collective
judgment of physicians/surgeons.
Public awareness and patient education are critical to improvements in health care. Fortunately, web-based resources
and media are making this knowledge more accessible to all. However, the complexities of CHD often make it difficult even
for experts to provide a focused explanation as well as answer all the queries.
Although there are several textbooks on the various aspects of CHD, there are very few that are focused yet comprehensive
to address all aspects of the care required for this special population. For medical/postgraduate students and practitioners,
quite frequently a lot of time is spent in referring to various resources in order to pull together complete diagnostic and
management strategies for one disease!
This book entitled, A Comprehensive Approach to Congenital Heart Diseases is designed to address all the practical aspects
that a health provider needs to know to deliver excellent care to the children and adults with CHD. In this book a whole-
hearted attempt has been made to cover all aspects from embryology, fetal malformations, pathology, clinical approach,
diagnostic investigations, management issues, current interventions to the surgery/heart-lung transplantation for CHD.
Our ‘A to Z’ approach addresses transition of care into adulthood, long-term issues facing the adults with CHD including
pregnancy, contraception and gynecological issues. Multiple distinguished authors from all over India and abroad have
made heartfelt contributions to make this book come alive.
Just like the saying goes “It takes a village to raise a child", it takes a global effort to care for an individual born with
CHD from “womb to tomb”. This book hopes to reach a wide global audience comprising but not limited to medical/
postgraduate students, nurse specialists, general practitioners, pediatricians, pediatric and adult cardiologists, as well as
cardiac surgeons.
This book has three editors representing the three generations who have witnessed the major advancements in this
field since the first “blue baby” operation. We hope to blend the global literature, new technology and our Indian and
international work experience to bring the best to our readers.
As the Editor-in-Chief, I (Dr IB Vijayalakshmi) have enjoyed collaborating with Dr P Syamasundar Rao who brings his
vast experience to this book, and Dr Reema Chugh who is a specialist in adult congenital heart disease/heart disease in
pregnancy in the United States. My special thanks to my associate Dr Chitra Narasimhan for her dedicated and diligent
support. I am extremely grateful to her for working beyond the call of her duties. I am grateful to Dr Pradeep Vaideeswar,
a pathologist par excellence, for writing the pathology section and sharing excellent pictures of pathological specimens
gathered during his distinguished career, and to Dr Prasanna Simha for writing on the surgical management of various
CHDs, and to Mr P Madhusudan for drawing explicit diagrams. We express our sincere gratitude to living legends, Dr S
Padmavati for writing the prologue and Dr Joseph K Perloff for writing the foreword.
As a co-editor, I (Dr P Syamasundar Rao) thank Dr Vijayalakshmi for inviting me to co-edit the book with her and for asking
me to contribute several chapters for this book. I have immensely enjoyed these tasks and feel delighted that I was able to
pass on the knowledge that I acquired from my teachers, Drs Lavanya Muhkerjee (Andhra Medical College, Visakhapatnam,
India), Herman W Lipow (Good Samaritan Hospital, Phoenix, Arizona, USA), Norman J Sissman (Stanford University, Palo
Alto, California, USA), Jerome Liebman (Case-Western Reserve University, Cleveland, Ohio, USA), and Leonard M Linde
(UCLA Medical Center, Los Angeles, California, USA) as well as from many pediatric cardiology and cardiovascular surgery
http://vip.persianss.ir
colleagues that I, over the years, had the opportunity to interact with at Medical College of Georgia, Augusta, Georgia, USA;
King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; University of Wisconsin Medical School, Madison,
Wisconsin, USA; Saint Louis University School of Medicine, St Louis, Missouri, USA and University of Texas-Houston Medical
A Comprehensive Approach to Congenital Heart Diseases
IB Vijayalakshmi
P Syamasundar Rao
Reema Chugh
xvi
Contents
Section 1: Embryo to the Neonate
Section 2: Basics
http://vip.persianss.ir
Section 3: Defects in Atriovenous and Pulmonary Arteriovenous Connections
A Comprehensive Approach to Congenital Heart Diseases
contents
31. Congenital Mitral Valve Diseases 445
Neeraj Awasthy, Radhakrishnan S
32. Mitral Atresia 458
Duraisamy Balaguru, P Syamasundar Rao
33. Aortic Valve Diseases 468
Smita Mishra, Neeraj Awasthy
xx
Section 12: Miscellaneous
contents
62. Congenital Coronary Artery Anomalies 879
Nick Hayes, Shakeel Qureshi
63. Cardiac and Extracardiac Masses 894
Bhanu Duggal, Vijayalakshmi IB
64. Lutembacher Syndrome 908
Nagamani AC, Nagesh CM
65. Pulmonary Hypertension 917
Maddury Jyotsna, Madhavapeddi Aditya
66. Congenital Pericardial Diseases 944
Prasanna Simha Mohan Rao
67. Marfan Syndrome 946
Harold N Bass, Reema Chugh
68. Down Syndrome 960
Harold N Bass, Reema Chugh
xxi
http://vip.persianss.ir
Sec t i on
http://vip.persianss.ir
C hapter
Development of the
1 Cardiovascular System
INTRODUCTION through the streak. The cells destined to form the cranial
segments of the heart, the outflow tract, migrate first and
Cardiovascular system begins to develop by the middle of the the cells forming the more caudal portions, right ventricle,
3rd week of intrauterine life. Functioning of the heart starts by left ventricle and sinus venosus respectively, migrate in a
early 4th week of intrauterine life. It develops mainly from the sequential order. The cells proceed toward the cranium and
splanchnic mesoderm, which forms the primordial heart. This position themselves rostral to the oropharyngeal membrane
is the first major system to start functioning. and neural folds. The primordial heart tube is formed by 18
days.
PRIMORDIAL HEART The primordial myocardium is formed from the splanchnic
mesoderm surrounding the pericardial coelom. The heart
Endothelial strands appear from the angioblastic cords in is now a thin endothelial tube and is separated from the
the cardiogenic mesoderm by about the 3rd week. These primordial myocardium by cardiac jelly. The endothelial
comprise of myoblasts and blood islands (Figures 1A to C). lining becomes the endocardium.
These arrange in the form of cords, which canalize to form The primitive myocardium develops into the muscular
two heart tubes. The two tubes unite with the lateral fold of wall. The mesothelial cells arise from the external surface of
embryo to form a single tubular heart (Figures 2A to C). Heart the sinus venosus and spread over the myocardium and form
begins to beat by the 22nd to 23rd day. The flow of blood the visceral pericardium.
begins by the 4th week.
Position of the Heart Tube
Development of the Heart
After the onset of formation of the head fold, the heart and
The cardiac progenitor cells lie in the epiblast, immediately the pericardial cavity, which were at the cranial end, come
lateral to the primitive streak and from there, they migrate to lie ventral to the foregut and caudal to the oropharyngeal
A C
Figures 1A to C: A. Dorsal view of the embryo; B. Transverse section on the embryo; C. Cephalocaudal section of the embryo
http://vip.persianss.ir
1
EmBryo to thE NEoNAtE
B
A
C
Figures 2A to C: A. Transverse section of early presomite (17 days) embryo; B. Transverse section of 18 days embryo;
C. Transverse section of 22 days embryo
membrane. The heart will now occupy the thoracic region. the yolk sac through the vitelline vein. The blood from the
Thus, the heart becomes a continuous expanded tube, consisting sinus venosus reaches the primitive atrium and is controlled
of an inner endothelial lining and an outer myocardial layer. by the sinoatrial valves. It passes through the atrioventricular
It receives venous drainage at its caudal pole and begins to (AV) canal and then into the primary ventricle, bulbus cordis,
pump blood out of the first aortic arch into the dorsal aorta at truncus arteriosus and finally into the aortic sac. Then through
its cranial pole. the aortic arches the blood reaches the dorsal aortae.
The tubular heart develops alternate dilatations and
constrictions. They are from the cranial to caudal – truncus Formation of the Cardiac Loop
arteriosus, bulbus cordis, ventricle, atrium and sinus venosus.
The truncus arteriosus is continuous cranially with the aortic sac The straight heart tube normally loops or folds to the right and
and aortic arches. The sinus venosus receives three paired sets of this occurs mostly during the fourth week and is completed
veins, the umbilical, vitelline and common cardinal veins from by day 28. The cephalic (ventricle) portion of the heart tube
the chorion, yolk sac and body wall of the embryo respectively. is displaced ventrally, caudally and to the right and the caudal
The arterial and venous ends of the heart are usually fixed. As the (atrium) portion of the tube is displaced dorsally, cranially and
bulbus cordis and venrticle grows faster, they form a U-shaped to the left. Hence, the looping of the bulboventricular tube
tube called the bulboventricular loop (Figures 3A to D). leads the bulbus cordis (prospectively, the right ventricle)
The sinus venosus develops lateral expansions, the right to the right (D-loop) of the initial caudal segment, which is
and left horns. The heart elongates bends and gradually the primitive ventricle (prospectively, the left ventricle).
invaginates into the pericardial cavity. The dorsal mesocardium Simultaneously, individual regions of the tube are expanding
suspends the heart and the central part disappears and forms and differentiating such that by the end of folding the region
the transverse sinus. of the future atria lies craniodorsal to the future ventricular
region. The cardiac looping is one of the first manifestations
Circulation through the Primordial Heart of right-left asymmetry in the developing embryo.
4
The myogenic contractions start at the end of 4th week in Abnormalities of Cardiac Looping
utero by coordinated contractions. The blood enters the sinus
venosus from the embryo through the common cardinal veins; Dextrocardia is a condition where the heart lies on the right
from the developing placenta through the umbilical vein; from side of the thorax instead of the left and is caused because the
1
D
Figures 3A to D: Formation of cardiac loop. A. 22 days; B. 23 days; C. 24 days; D. Frontal view
of heart tube looping inside in the pericardial cavity
heart loops to the left instead of the right. This may coincide week and is completed by the 5th week. At the end of the 4th
with situs inversus, a complete reversal of the position of all week, the endocardial cushions from the dorsal and ventral
organs. Situs inversus, which occurs in 1/7,000 individuals, is wall of the AV canal begin to approach each other and fuse
usually associated with normal physiology, although there is a with the right and left AV canals. These are formed from
slight risk of cardiac defects. The patients with isomerism have the endocardial cushions and function as AV valves. The
replication of the right or left cardiac and visceral structures endocardial cushions are made of specialized extracellular
bilaterally. The spleen reflects the difference between right matrix or cardiac jelly.
and left isomerism with polysplenia occuring in left-sided
bilaterality, left isomerism and asplenia or hypoplastic spleen Partitioning of the Primordial Atrium
in right-sided bilaterality, right isomerism. These patients also
have increased incidence of other malformations, especially The atrial partitioning begins at the end of the 4th week of
heart defects. The genes regulating sidedness are expressed development. The septum primum, a thin crescent-shaped
during gastrulation. membrane descends from the roof of primitive atrium
towards the endocardial cushion. A gap, foramen primum,
Partitioning of the Primordial Heart appears between the free margin of the septum primum and
the endocardial cushion. The foramen primum acts as a shunt
The single heart tube now starts to partition to form chambers. for the oxygenated blood to pass through from the right to
The partitioning of the AV canal, the primordial atrium and the left atrium. The septum primum merges with the fused 5
the primitive ventricle begins around the middle of the 4th endocardial cushion to form the primordial AV septum.
http://vip.persianss.ir
1 The perforations produced by programed cell death appear between the atria and consequently an oval foramen or
in the central part of the septum primum, before the foramen foramen ovale is formed. The cranial part of the septum
primum disappears. As the septum primum fuses with the primum disappears and the remaining part forms a flap-like
EmBryo to thE NEoNAtE
endocardial cushions, the perforations coalesce to form the valve of the ovale foramen.
foramen secundum and the foramen primum obliterates Before birth, the foramen ovale transmits the oxygenated
(Figures 4A to F). blood from the right to the left atrium. The left to right flow
The foramen secundum ensures free flow of the oxygenated is prevented by the septum primum, closing on the septum
blood from the right to the left atrium. The septum secundum secundum (Figures 5A and B). After birth, the valve of the
grows from the ventrocranial wall to the right of the septum oval foramen fuses with the septum primum and closes the
primum. The septum secundum forms an incomplete partition ovale foramen. The oval depression in the lower part of
A B C
D E F
Figures 4A to F: Atrial septum formation by the actively growing ridges
6
A B
Figures 5A and B: Ventral view of coronal section through the heart showing right and left atrial development
1
interatrial septum of the right atrium is the oval fossa and is a rise to the coronary sinus (drains blood from the coronary
remnant of the oval foramen or foramen ovale. circulation of the heart muscle) and the small oblique vein
of the left atrium The right horn is incorporated into the right
Changes in the Sinus Venosus atrium and the remainder of the right atrium forms the auricle.
The two parts are demarcated internally by a vertical ridge,
Initially the sinus venosus opens into the centre of the right the crista terminalis and externally by a shallow groove, the
atrium and its right and left horns are about the same size. sulcus terminalis (Figures 5A and B).
There is progressive enlargement of the right horn due to two • The cranial part of the crista terminalis forms the right
left to right shunts of blood. The first shunt is the transformation sinoatrial valve
of the vitelline and umbilical veins. The second shunt occurs • The caudal part forms the valves of the IVC and the
when the anterior cardinal veins become connected by an coronary sinus
anastomosis. This communication shunts blood from the left • The left sinoatrial valve is incorporated into the interatrial
to the right anterior cardinal vein. This shunt becomes the septum.
left brachiocephalic vein. The right anterior cardinal vein and
the right common cardinal vein become the superior vena Formation of the Left Atrium
cava (SVC). The right horn, by the end of the 4th week, is
noticeably larger than the left. The sinoatrial orifice moves to The left atrial wall is mostly smooth because it is formed by
the right and opens in the part of the primitive atrium that will the incorporation of the primitive pulmonary veins. The veins
become the adult right atrium. develop as an outgrowth of the dorsal atrial wall to the left
The consequence of the two left to right venous shunts of the septum primum. As the atrium expands, the primitive
causes the left horn of the sinus venosus to decrease in size pulmonary veins and its main branches are gradually
and its importance. The right horn enlarges and receives all incorporated into the wall of the left atrium.
the blood from the head and neck, through the SVC; and from
the placenta and caudal regions through the inferior vena cava Partitioning of the Primordial Ventricle
(IVC) (Figures 6A and B).
Initially, the sinus venosus is a separate chamber. The left The septum formation starts in the AV canal and by the end of the 7
horn of the sinus venosus ceases to grow and eventually gives fourth week two cushions of mesenchyme, the AV endocardial
http://vip.persianss.ir
1
EmBryo to thE NEoNAtE
A B C D
Figures 7A to D: Formation of the atrioventricular canal by the fusion of the endocardial cushions
cushions, appear at its anterior and posterior borders. The AV examples of cardiovascular teratogens include rubella virus
canal initially gives access only to the primitive left ventricle and thalidomide. Others include retinoic acid (accutane),
and is separated from the bulbus cordis by the bulbo (cono) alcohol and many other compounds. The cardiac defects have
ventricular flange. As the AV canal enlarges to the right, the been linked to maternal diseases such as the insulin-dependent
blood passing through the AV orifice, now has direct access to diabetes and hypertension. The chromosomal abnormalities
the primitive left as well as the primitive right ventricle. are associated with heart malformations and 6 to 10 percent
The two lateral AV cushions appear on the right and left of newborns with cardiac defects have an unbalanced
borders of the canal, along with the anterior and posterior chromosomal abnormality. Furthermore, 33 percent of
endocardial cushions. The anterior and posterior cushions children with chromosomal abnormalities have a congenital
project into the lumen and fuse, resulting in a complete heart defect, with an incidence of nearly 100 percent in
division of the canal into the right and left AV orifices, by the children with Trisomy 18. Finally, cardiac malformations are
end of the 5th week (Figures 7A to D). associated with a number of genetic syndromes, including
craniofacial abnormalities, such as DiGeorge, Goldenhar and
Development of the Atrioventricular Valves Down’s syndromes.
The genes regulating cardiac development are being
The AV endocardial cushions fuse and each AV orifice is identified and mapped and mutations that result in heart defects
surrounded by proliferations of mesenchymal tissue. The are being discovered. For example, mutations in the heart-
bloodstream hollows out and thins the tissue on the ventricular specifying gene NKX2.5 on chromosome 5q35, can produce
surface of these proliferations to form valves and they remain atrial septal defects (secundum type), tetralogy of Fallot, and
attached to the ventricular wall by muscular cords. The AV conduction delays in an autosomal dominant fashion. The
muscular tissue in the cords degenerates and is replaced by mutations in the TBX5 gene result in Holt–Oram syndrome,
dense connective tissue. The valves consist of connective characterized by preaxial (radial) limb abnormalities and
tissue covered by endocardium. They are connected to thick atrial septal defects. The defects in the muscular portion
trabeculae in the wall of the ventricle, the papillary muscles of the interventricular septum may also occur. Holt–Oram
by means of the chordae tendineae (Figures 8A to C). The two syndrome is one of the groups of heart-hand syndromes,
valve leaflets constituting the bicuspid (or mitral) valve forms illustrating that the same genes may participate in multiple
in the left AV canal and three valve leaflets constituting the developmental processes. For example, TBX5 regulates
tricuspid valve forms on the right side. forelimb development and also plays a role in septation of
the heart. Holt–Oram syndrome is inherited as an autosomal
Clinical Embryology dominant trait with a frequency of 1/100,000 live births.
Mutations in a number of genes regulating production
Heart Defects: The heart and vascular abnormalities is the of sarcomere proteins cause hypertrophic cardiomyopathy
largest category of human birth defects, accounting for 1 that may result in sudden death in athletes and the general
percent of malformations among live-born infants. The population. The disease is inherited as autosomal dominant
incidence among stillborns is 10 times as high. It is estimated and most mutations (45%) target the β-myosin heavy chain
that 8 percent of cardiac malformations are due to genetic gene (14q11.2). The result is cardiac hypertrophy due
factors, 2 percent are due to environmental agents while most to disruption in the organization of cardiac muscle cells
are due to a complex interplay between the genetic and the (myocardial disarray), which may adversely affect cardiac
8 environmental influences (multifactorial causes). The classic output and/or conduction.
1
Atrial septal defect is caused either by excessive cell The Ebstein’s anomaly is a condition where the tricuspid
death and resorption of the septum primum or by inadequate valve is displaced towards the apex of the right ventricle. The
development of the septum secundum. Depending on the valve leaflets are abnormally positioned and the anterior one
size of the opening, considerable intracardiac shunting may is usually enlarged. As a result, there is hypertrophy of the
occur from left to right. The most serious abnormality in this right atrium with a small right ventricle.
group is complete absence of the atrial septum. This condition
known as common atrium or cor-triloculare biventriculare, Septum Formation in the Truncus Arteriosus and
is always associated with serious defects elsewhere in the Conus Cordis
heart.
Occasionally, the oval foramen closes during prenatal life. In the truncus, pairs of opposing ridges appear by the fifth
This abnormality, premature closure of the oval foramen, leads week. These ridges called the truncus swellings or cushions,
to massive hypertrophy of the right atrium and ventricle and lie on the right superior wall (right superior truncus swelling)
underdevelopment of the left side of the heart. Death usually and on the left inferior wall (left inferior truncus swelling).
occurs shortly after birth. The right superior truncus swelling grows distally and to the
The endocardial cushions of the AV atrioventricular canal left and the left inferior truncus swelling grows distally and
not only divides this canal into a right and left orifice, but to the right. Hence, while growing toward the aortic sac the
also participates in formation of the membranous portion swellings twist around each other, making the spiral course
of the interventricular septum and in closure of the ostium of the future septum. Once the fusion is complete, the ridges
primum. This region has the appearance of a ‘cross’, with form the aorticopulmonary septum, dividing the truncus into
the atrial and ventricular septum forming the post and the AV an aortic and a pulmonary channel.
cushions forming the crossbar. The integrity of this ‘cross’ is At the same time similar swellings (cushions) develop
an important sign in ultrasound scans of the heart. Whenever along the right dorsal and left ventral walls of the conus
the cushions fail to fuse, the result is a persistent AV canal, cordis. These conus swellings grow towards each other and
combined with a defect in the cardiac septum. This septal distally to unite with the truncus septum. The fusion of the
defect has an atrial and a ventricular component, separated by two conus swellings causes the septum to divide the conus
abnormal valve leaflets in the single AV orifice. into an anterolateral portion (the outflow tract of the right
Occasionally, endocardial cushions in the AV canal ventricle) and a posteromedial portion (the outflow tract of
partially fuse. The result is a ostium primum defect but there the left ventricle) (Figures 9A and B).
is closure of the interventricular septum. This defect is usually The arterial outlet, at the same time, undergoes a process
associated with a cleft in the anterior leaflet of the mitral of leftward shifting and differential growth that leads to the
valve. disappearance of the bulboventricular flange; the resorption of
The tricuspid atresia, which involves obliteration of the the caudal extreme; and leftward shifting of the conus, closer
right AV orifice, is characterized by the absence or fusion of to the anterior AV canal cushion. The differences in cell growth
the tricuspid valves. It is always associated with: of the outlet septum lead to a lengthening of the segment of
a. Patency of the oval foramen. smooth muscle beneath the pulmonary valve (conus). This
b. Ventricular septal defect. process separates the tricuspid and pulmonary valves. In
c. Underdevelopment of the right ventricle. contrast, the segment beneath the aortic valve disappears, so 9
d. Hypertrophy of the left ventricle. that there is fibrous continuity of the mitral and aortic valves.
http://vip.persianss.ir
1 Neural crest cells, originating in the edges of the neural the subaortic and the subpulmonary conal free walls, that is,
folds in the hindbrain region, migrate through the pharyngeal failure of subsemilunar conal free wall resorption.
arches 3, 4 and 6 to the outflow region of the heart which
EmBryo to thE NEoNAtE
they invade. Here, they contribute to the endocardial cushion Semilunar Valves
formation in both the conus cordis and truncus arteriosus. The
abnormal proliferation, migration or differentiation of these As the completion of the partitioning of the truncus, primordia
cells results in congenital malformations in this region, such of the semilunar valves occurs, small tubercles become visible
as tetralogy of Fallot, pulmonary stenosis, persistent truncus on the main truncal swellings. One of each pair belongs to
arteriosus and transposition of the great vessels. Neural crest the pulmonary and the aortic channels, respectively. A third
cells also contribute to craniofacial development; hence it is tubercle appears in both channels, opposite the fused truncal
not uncommon to see facial and cardiac abnormalities in the swellings. The tubercles slowly hollow out at their upper
same patient. surface, forming the semilunar valves (Figures 10 and 11).
Recent evidence shows that neural crest cells contribute to the
Septum Formation in the Ventricles formation of these valves.
By the end of the 4th week, the two primitive ventricles Aortic Arch Derivatives
begin to expand. This also includes continuous growth of the
myocardium on the outside and continuous diverticulation The pharyngeal arches develop during the 4th week and
and trabecula formation on the inside. they are supplied by arteries directly from the aortic sacs.
The medial walls of the expanding ventricles become The aortic arches terminate in the dorsal aorta and six pairs
opposed and gradually merge and this forms the muscular of arch arteries are formed (Figure 12A). Among them, the
interventricular septum. If the two walls do not merge first 2 disappears, when the 6th artery appears. The remaining
completely, a deep apical cleft between the two ventricles arteries will arrange into its final fetal arterial arrangement,
appears. The space between the free rim of the muscular during the 8th week.
ventricular septum and the fused endocardial cushions permits The small portion of the first arch artery remains as maxillary
communication between the two ventricles. artery. The second pair of aortic arch arteries persists as stems
The interventricular foramen, above the muscular portion of the stapedial arteries. In the third pair of arch arteries, the
of the interventricular septum, decreases on completion of proximal part forms the common carotid arteries; distal part
the conus septum. On further development, the outgrowth of joins with the dorsal aorta to form the internal carotid arteries.
the tissue from the inferior endocardial cushion along the top The fourth arch artery on left side forms part of the arch
of the muscular interventricular septum closes the foramen. of aorta. The right fourth aortic arch forms the proximal part
This tissue fuses with the abutting parts of the conus septum. of the right subclavian artery. The distal part of subclavian
Complete closure of the interventricular foramen forms the artery is formed from the right dorsal aorta and the right 7th
membranous part of the interventricular septum (Figure 9C). intersegmental artery. The left subclavian artery develops
from the left 7th intersegmental artery. As there is differential
Abnormalities of Conotruncal Development growth, the subclavian artery comes to lie close to the left
common carotid artery.
The conotruncus is one of the most common sites of The fate of the fifth pair of aortic arches in 50 percent of the
cardiac abnormalities, as it requires normal development embryos is rudimentary and it soon degenerates. They do not
and proliferation of multiple cell types (secondary heart develop in the other 50 percent. The proximal part of the sixth
field, neural crest cells, myocardium , endocardium). There pair of arch artery on the left side persists as proximal part of
are many disorders involving the conotruncal region such left pulmonary artery. The distal part of this arch artery passes
as common arterial trunk, double outlet right ventricle, from the left pulmonary artery to the dorsal aorta to form the
interrupted aortic arch, transposition of the great arteries, arterial shunt called ductus arteriosus.
tetralogy of Fallot and ventricular septal defect. The tetralogy The proximal part of the right sixth arch artery persists as
of Fallot occurs due to an unequal division of the conus the proximal part of right pulmonary artery and the distal part
resulting from the anterior displacement of the conotruncal degenerates (Figures 12B and C). The transformation of the
septum. The persistent truncus arteriosus results when the sixth pair of aortic arches, determines the course of recurrent
conotruncal ridges fail to fuse and to descend toward the laryngeal nerves. On the right, because the distal part of right
ventricles. The transposition of the great vessels occurs sixth aortic arch degenerates, the right recurrent laryngeal
when the conotruncal septum fails to follow its normal spiral nerve hooks around right subclavian artery, a derivative
course and runs straight down. Van Praagh has said that of the fourth aortic arch artery. The left recurrent laryngeal
the growth of the subaortic conal free wall and resorption nerve hooks around the ductus arteriosus, formed by the distal
10 of the subpulmonary conal free wall results in transposition part of sixth arch artery on the left side. As the arterial shunt
of the great arteries. Also, double-outlet right ventricle is involutes after birth, the nerve hooks around the ligamentum
caused due to the continued persistence and growth of both arteriosum and the arch of the aorta.
1
A B C
Figures 10A to C: Transverse section through the truncus arteriosus
A B C
Figures 11A to C: Transverse sections through the truncus arteriosus at the level of the semilunar valves.
A. At 5 weeks; B. At 6 weeks; C. At 7 weeks
Aortic Arch Anomalies Aortic Arches and Other Branches of Dorsal Aorta
Since many changes are involved in the transformation of the The aortic sacs arise from aortic arches and terminate in dorsal
embryonic pharyngeal arch system of arteries into the adult aorta, by the fourth to fifth weeks. Initially aorta is paired
arterial pattern, anomalies occur. Anomalies result from either and run through the body. Soon, single dorsal aorta caudal to 11
disappearance or persistence of parts of the aortic arch arteries. aortic arches is formed.
http://vip.persianss.ir
1
EmBryo to thE NEoNAtE
A B
C
Figures 12A to C: A. Aortic arches and dorsal aortae; B and C. Final form of the aortic arch arteries
Intersegmental Arteries distal part gets obliterates and remains as medial umbilical
The dorsal intersegmental arteries carry blood to somites. ligaments.
The vertebral artery is formed from the dorsal intersegmental
artery in the neck and the intercostal arteries are formed by the Clinical Correlates
dorsal intersegmental arteries. The lumbar arteries are formed
by abdominal intersegmental arteries. The fifth pair of the Arterial system defects: Normally, the ductus arteriosus is
lumbar intersegmetal arteries forms the common iliac arteries. functionally closed through the contraction of its muscular
The lateral sacral arteries form the sacral intersegmental wall shortly after birth to form the ligamentum arteriosum.
arteries. The caudal end of the dorsal aorta forms the median The anatomical closure occurs by the proliferation of intima
sacral artery. by 1 to 3 months.
In the coarctation of the aorta, the aortic lumen below the
Fate of the Vitelline origin of the left subclavian artery is significantly narrowed.
Since the constriction may be above or below the entrance of
The vitelline arteries pass to the yolk sac and the primitive the two types (preductal and postductal) may be distinguished
gut. The three vitelline arteries that remain are the celiac trunk (Figures 13A and B). The cause of the aortic narrowing is
to the foregut, the superior mesenteric artery to the midgut and primarily an abnormality in the media of the aorta, followed
the inferior mesenteric artery to the hind gut. by intimal proliferations. In the preductal type, the ductus
arteriosus persists; in the postductal type, which is more
Umbilical Arteries common, this channel is usually obliterated. In the latter case,
collateral circulation between the proximal and the distal parts
12 The umbilical arteries pass through the connecting stalk and of the aorta is established by large intercostal and internal
carry poorly oxygenated blood. The proximal part forms the thoracic arteries. In this manner, the lower part of the body is
internal iliac arteries and the superior vesical arteries. The supplied with blood.
1
A B
Figures 14A and B: Abnormal origin of the right subclavian artery
The abnormal origin of the right subclavian artery occurs In a double aortic arch, the right dorsal aorta persists
when the artery is formed by the distal portion of the right between the origin of the seventh intersegmental artery and
dorsal aorta and the seventh intersegmental artery (Figures its junction with the left dorsal aorta (Figure 15A). A vascular
14A and B). The right fourth aortic arch and the proximal part ring surrounds the trachea and the oesophagus and commonly
of the right dorsal aorta are obliterated. With shortening of compresses these structures, causing difficulties in breathing
the aorta between the left common carotid and left subclavian and swallowing (Figure 15B).
arteries, the origin of the abnormal right subclavian artery
finally settles just below that of the left subclavian artery. Since Development of Veins Associated with the Heart
its stem is derived from the right dorsal aorta, it must cross the
midline behind the oesophagus to reach the right arm. This The three paired veins drain into the tubular heart. The
location does not usually cause problems with breathing and vitelline veins return poorly oxygenated blood from the
swallowing since neither the trachea nor the oesophagus is yolk sac. The umbilical veins carry well-oxygenated blood
severely compressed. from the primordial placenta. The common cardinal veins 13
http://vip.persianss.ir
1
EmBryo to thE NEoNAtE
A B
Figures 15A and B: Double aortic arch. A. Persistent right dorsal aorta; B. Formation of the vascular ring around the trachea and esophagus
Vitelline Veins
The vitelline veins drain from the yolk sac to the embryo.
After the formation of the septum transversum, the vitelline
veins enter the venous end called the sinus venosus. As the
liver primordium grows into the septum transversum, the
hepatic cords anastomose around the primordia of the hepatic
sinusoids.
The left common cardinal vein is obliterated at 10 weeks Figure 16: Main intraembryonic and extraembryonic vessels
and all that remains of the left sinus horn is the oblique vein
of the left atrium and the coronary sinus. The hepatic veins
drain from the remains of right vitelline vein. The portal vein
develops as an anastomotic network formed by the vitelline derivative of posterior cardinal vein is the root of azygos
veins around the duodenum. vein and common iliac vein. The subcardinal veins connect
The right umbilical vein and the caudal part of the left through the subcardinal anastomosis. It forms the stem of
umbilical vein between the liver and the sinus venosus the left renal vein, the suprarenal vein, the gonadal veins
degenerates. The persistent left umbilical vein forms the and a segment of the IVC. The supracardinal veins in adult
ductus venosus which is large venous shunt that develops form the azygos and hemiazygos veins and part of the IVC
within the liver. (Figures 17A and B).
The cardinal veins are the main venous drainage system
of embryo. The anterior and posterior cardinal veins drain Development of the Inferior Vena Cava
from the cranial and the caudal part of embryo. They join the
common cardinal vein and enter into the sinus venosus. The IVC is composed of four segments: hepatic, suprarenal,
The anterior cardinal vein anastomosis forms the left renal, and infrarenal. The hepatic segment is formed from the
brachiocephalic vein. The caudal part of the left cardinal vitelline vein. The right subcardinal vein forms the suprarenal
vein disappears. The SVC is formed from the right segment by formation of the subcardinal-hepatic anastomosis.
anterior cardinal vein and the right common cardinal The renal segment develops from the right suprasubcardinal
vein. The posterior cardinal vein develops as vessels of and postsubcardinal anastomoses. It is generally accepted
mesonephros and the developing transient kidneys. These that the infrarenal segment formed by the right supracardinal
14 veins disappear with these kidneys. The remaining adult vein.
1
ANOMALIES OF THE VENA CAVAE isolated angiogenic cell islets into a complex, four-chambered
structure. The critical period for development of anomalies
The anomalies of the vena cavae are double SVC, left SVC, is 3–6 weeks. Hence, knowledge of cardiac embryology is
Absence of hepatic segment of IVC, double IVC, azygos necessary to understand the congenital heart defects and to
continuation of IVC etc. These anomalies have been discussed develop strategies for prevention.
in chapter 15.
The embryological record is almost always abbreviated in
FETAL CIRCULATION accordance with the tendency of nature (to be explained on
the principle of survival of the fittest) to attain her needs by
Fetal Circulation has been discussed in Chapter 2. the easiest means.
— Francis Maitland Balfour
CONCLUSION
SUGGESTED READING
The cardiovascular system is the first functional system in
1. Sadler TW. Langmans Medical Embryology 11th edition.
embryo. The single heart tube begins to beat at 23 days of
Chapter 12.
development. The entire process of formation of cardiovascular 2. Keith L Moore. The developing Human Clinically oriented
structures is completed within one month after the first 20 embryology, 8th edition.
days of embryogenesis. This amazing process transforms
15
http://vip.persianss.ir
C hapter
2 Fetal Circulation
Fetal Circulation
fetus, i.e. placenta. There is mixing of venous return and
preferential streaming.
4. The resistance within the placenta is extremely low and this
promotes shunting of blood to the placenta. Thus, there is
low impedance and high flow in the placental circulation.
The placenta is a richly vascularized organ and serves as
the site for oxygenation and nutrient delivery to the fetus
and carries away its wastes. The exchange of materials in
the placenta is via diffusion.
5. There is high impedance and low flow in the pulmonary
circulation.
6. The pressures in the right or venous system are higher than
the pressures in the left or arterial system.16
7. The three cardiovascular fetal shunts, ductus venosus,
ductus arteriosus and the foramen ovale, are essential
distributional arrangements, making the fetal circulation,
a flexible and adaptive system for intrauterine life.17 These
shunts provide blood flow pathways specific to the fetus
and are important for maintaining the parallel circulation.
8. Long-chain fatty acids are the dominant energy source in Figure 1: Anatomy of the fetal circulation and the oxygen saturations
the adult, whereas fetal myocardial energy requirements in the various chambers and vessels. RV = Right ventricle; LV = Left
ventricle
are primarily met by lactate extraction.
9. The concentration of hemoglobin in the fetal blood is about
50 percent greater than in maternal blood. At a particular passes through the direct shunt, the ductus venosus (DV).19,20
oxygen partial pressure, fetal hemoglobin can carry 20 to The fetal DV is a slender trumpet-like shunt, connecting into
30 percent more oxygen than the maternal hemoglobin. the inferior vena cava (IVC), near its junction with the right
In addition, the presence of fetal hemoglobin means that atrium (RA).18 The DV and the umbilical vessels are kept open
the organs in the fetus are able to extract oxygen at low by the mechanical effect of the flow through them. The better
saturations.15 oxygenated blood from the DV remains on the posterior and
leftward aspect of the IVC and tends to stream separately from
ANATOMY OF THE FETAL CIRCULATION the extremely desaturated systemic venous blood, which is
returning from the lower portions of the body.15,21
The fetal circulation works differently from that of the baby On reaching the heart, the IVC blood is effectively divided
after birth, mainly because the lungs are not in use in the into two streams. A highly oxygenated stream is preferentially
fetus. The fetus obtains oxygen and nutrients from the mother shunted through the next shunt in the fetal circulation, the
through the placenta and the umbilical cord, while a baby foramen ovale (FO), into the left atrium (LA). The other stream
after birth acquires oxygen from its lungs. The embryo/fetus passes into the RA where it is joined by the deoxygenated
is attached to placenta via the umbilical cord. The anatomy of stream from the superior vena cava (SVC) and this is directed
the fetal circulation is shown in Figure 1. through the tricuspid valve into the right ventricle (RV). The
The deoxygenated blood passes to the placenta via the two mechanical effect of the streaming of the IVC blood into the
umbilical arteries. These arteries arise from the right and left LA and the physical relationship of the IVC to the LA, keeps
internal iliac arteries. The fetal blood is oxygenated in the the FO patent in the fetus.
placenta and is returned to the fetus via the umbilical veins. The preferential shunting of the more highly oxygenated
Initially, there is a right and a left umbilical vein and they IVC blood through the FO appears to be due to various
empty into the hepatic venous sinusoids. The right umbilical reasons:
vein regresses completely, early in fetal life.18 1. The angle at which the DV inserts into the IVC–RA
The blood flow in the umbilical vein splits in the liver. Some junction, directs most of the richly oxygenated blood
of it goes into the hepatic veins and the portal system of the across the FO and into the LA.22
liver. In fetal lambs, the proportions vary and on an average 2. The crista dividens, forming the upper margin of the FO
about 55 percent (range 20–90%) passes through the ductus (free margin of the septum secundum) overrides the IVC.23
venosus. In the human fetus, 20 to 30 percent of the blood flow The free edge of the lower margin of the FO, formed by the 17
http://vip.persianss.ir
1 septum primum, is on the left side of the atrial septum and the undersurface of the liver, represents the obliterated
the FO is kept open by the IVC stream. umbilical vein.
3. The IVC valve or the Eustachian valve diverts the IVC 3. The ligamentum venosum, lying within its fissure on the
Embryo to the Neonate
blood stream towards the atrial septum.24 undersurface of the liver, continuing as the ligamentum
4. It is likely that the higher velocity of the DV bloodstream teres and terminating at the IVC, represents the obliterated
(55 cm/s) as compared to the lower velocity of the distal DV.
IVC (15 cm/s) bloodstream contributes to maintaining the 4. The fossa ovalis on the interatrial septum, which is ‘probe
preferential distribution of DV blood across the FO.25 patent’ in about 10 percent of normal subjects, represents
The Eustachian valve and the lower portion of the atrial the FO.
septum move in unison during the phases of the cardiac cycle. 5. The ligamentum arteriosum, between the aortic arch and
They move either to the left to facilitate movement of blood the left pulmonary artery, with the recurrent laryngeal
through the FO or to the right to enhance flow through the nerve in close proximity, represents the DA.
tricuspid valve.26 This preferential streaming of the DV and
the left hepatic venous blood through the FO distributes the PHYSIOLOGY OF THE FETAL CIRCULATION
highly oxygenated blood to the LA and this mixes with the
small amount of deoxygenated blood from the lungs, draining The fetal circulatory physiology has been based on animal
through the pulmonary veins, before entering the left ventricle data. Ultrasound in obstetrics has been used increasingly to
(LV) through the mitral valve. From the LV, the ascending provide physiological data from human fetuses. There are now
aorta delivers this oxygen-rich blood to the coronary arteries, a growing number of human studies, which have investigated
the head and neck vessels and the upper extremities. Only a the human physiology, with results that are similar, but not
small portion of left ventricular cardiac output (10%) traverses identical to those from animal studies.17 The human fetus
the aortic arch and supplies blood flow to the thoracic aorta.27 seems to circulate less blood through the placenta, shunt less
The most deoxygenated blood returns to the heart from through the DV and FO, but directs more blood through the
the upper body through the SVC and from the myocardium lungs than the fetal sheep. There are also substantial individual
through the coronary sinus. This blood, in addition to the variations and the pattern changes with gestational age.17
IVC’s anteriorly streamed flow (venous return from the lower
body and hepatic circulation), is directed across the tricuspid Fetal Blood Volume
valve into RV and then ejected into pulmonary artery (PA).15
Only about 5 percent or less of the deoxygenated blood from The blood volume in the human fetus is between 10 and 12
the SVC flows through the FO into the left atrium in the percent of the body weight as compared with 7 to 8 percent in
normal fetus.25 the adults.28 This is mainly due to the large volume of blood
As the lungs of the fetus are inactive, most of the in the placenta, which decreases with gestation.
deoxygenated blood from the RV is diverted via the third shunt, Studies have indicated a volume of 110 to 115 mL/kg,
the ductus arteriosus (DA), from the PA into the descending which is comparable with experimental sheep studies.29 The
aorta, distal to the left subclavian artery. The muscular DA fetus, when compared with adults, is capable of much faster
is kept open by the active dilatation of both locally produced regulation and restoration of the blood volume due to the high
and circulating prostaglandins (PGE2 and possibly PGI2). In diffusion rates between the fetal compartments.28
the fetus the DA is as large as the aorta. Only a small amount
of the RV output enters the pulmonary circulation, while the Fetal Arterial and Venous Blood Pressure
remaining major portion crosses the DA and then into the
descending aorta. The reduced blood flow to the lungs is also The human fetal mean arterial pressure was measured to
reflected by the relatively smaller branch pulmonary arteries be 15 mm Hg during cordocentesis at the gestational age of
in utero and a large arterial ductus and descending aorta. 19 to 21 weeks.30 Intrauterine recordings of the human fetal
The lower half of the body is thus supplied with relatively intraventricular pressure suggest that the systemic systolic
desaturated blood. This blood supplies the abdominal viscera pressure increases from 15 to 20 mm Hg at 16 weeks to 30 to 40
and the lower limbs and is shunted, via the umbilical arteries, mm Hg at 28 weeks.31 The results did not show any substantial
which branch from the internal iliac arteries, to the placenta for difference between the two ventricles and in the diastolic
oxygenation.15,18 ventricular pressure. The umbilical venous pressure, recorded
In adult anatomy the following remains of the fetal during cordocentesis and corrected for amniotic pressure,
circulation can be readily recognized.18 increased from 4.5 mm Hg at 18 weeks to 6 mm Hg at term.32
1. The medial umbilical ligament on each side, passing from
the superior vesical branch of the internal iliac artery to the Fetal Cardiac Function
umbilicus, represents the obliterated umbilical arteries.
18 2. The round ligament or ligamentum teres, lying in the free The fetal myocardium is structurally and functionally immature
edge of the falciform ligament and then in its groove on compared with that of the older child or adult. The structural
details of the fetal heart are organized during the embryonic Table 1
2
period. The fetal heart continues to grow and is dependent on Showing differences between fetal/neonatal and adult
the physical environment including blood flow for its normal myocardial physiology
Fetal Circulation
growth. In many ways, the fetal myocardium differs from the
Feature Fetus/Neonate Adult
adult myocardium. The fetal myocardium is composed of
nearly 60 percent of non-contractile elements as compared to Cardiac output HR dependent SV and HR
30 percent in the adult myocardium.33 Early fetal myocytes Starling response Limited Normal
can undergo replication with development of hyperplasia or Compliance Less Normal
an increase in cell number, whereas mature adult myocytes Afterload Limited Effective
undergo hypertrophy or increase in cell size. The myofibrils compensation
density increases in early pregnancy, but the contractility Ventricular High Relatively low
continues to improve during the second half of pregnancy.34 interdependence
The relaxation properties of the fetal myocardium differs from
HR = Heart rate; SV = Stroke volume
those of the adult. This may be due to the diminished function
of the sarcoplasmic reticulum and greater dependence on
the sodium-calcium exchanger process to remove cytosolic-
calcium in the fetus.35 Fetal heart is much stiffer than the adult pressure can affect both the ventricles, but the RV is affected
heart, with impaired relaxation properties relative to the adult. to a greater degree than the LV in the developing fetus.41
The ‘stiffness’of the fetal myocardium is also partly due to Thus in situations of increased preload or afterload, the RV
the constraint of the pericardium, lungs and chest wall.36 The will manifest hypertrophy, dilatation or dysfunction before
stiffness and impaired relaxation of the fetal myocardium is the LV.
reflected by the Doppler echocardiography done across the In the fetal heart, due to the wide communication between
atrioventricular valves. In the fetus, E : A ratio will typically the atria, there is equalization of pressures. Also, due to the
be less than 1, as passive early filling is impaired and active patency of the DA, there is equalization of pressures in the
atrial contraction is primarily responsible for emptying the aorta and pulmonary artery. As the atrial and great vessel
atrium.37 The E : A ratio is usually >1 in adults. pressures are equal, in the absence of aortic and pulmonic
The fetal heart has a limited preload reserve and hence stenosis, the ventricular pressures are also equal with a systolic
a limited capacity to increase stroke volume by increasing pressure of approximately 70 mm Hg using amniotic pressure
diastolic filling pressure, the RV even less than the left. as zero.27
Though the Frank-Starling mechanism operates in the fetal
heart, it does so till a point is reached, after which any increase Fetal Cardiac Output and Distribution
in preload will result in a plateau without any further increase
in the stroke volume.38 Fetal cardiac output is controlled In adults, the circulatory system is in series and as there are no
entirely by the changes in the fetal heart rate in contrast to the shunts, the LV and RV stroke volumes are equal. In the fetus,
stroke volume changes in the adult. Thus, heart rate may be the the circulation is in parallel and as a result of the intracardiac
single most prominent means of increasing cardiac output in and extracardiac shunting, the stroke volumes of the fetal LV
the fetus. There is immaturity of the sympathetic innervations and RV are not equal. Even though the pressures are equal,
of the fetal heart as compared to the parasympathetic. Thus, the RV stroke volume is more. This could be explained due
under stress the fetal cardiac output favors maintenance of the to the differences in afterload of the two ventricles. The fetal
umbilical blood flow and support of the myocardium, adrenal aortic isthmus is narrower than the ascending and descending
and brain.39 The differences between the fetal and adult aorta and this may functionally separate the upper and lower
myocardial physiology is shown in Table 1. body circulation to some extent.25
The pressure difference between the ventricles is minimal The fetal circulation is shunt dependent and is much more
in the fetus as compared to that in postnatal life. This is complex and hence the cardiac output must be expressed as
because the ventricles in the fetus are pumping in parallel the combined cardiac output (CCO).25 The estimated cardiac
into the systemic circulation.31 In fetal circulation as the RV output of the human fetus (553 mL/kg/min−1) is higher than
handles 55 percent of the combined ventricular output, it is that of sheep (450 mL/kg/min−1). The CCO is reported to be
larger and more dominant than the LV. This is confirmed on 210 mL/min at midgestation and 1900 mL/min at 38 weeks
echocardiographic evaluation of the human fetal heart. The in human fetus (Table 2).42 In addition, the right and left
wall thicknesses of both the ventricles in the fetal heart are ventricular outputs are more similar in the humans (56/44)
approximately equivalent. As compared to the LV, the RV has when compared with that in sheep (66/34).25 Thus, the ratio
a greater wall stress, which is due to the greater radius to wall of right to left ventricular output, which is about 2 : 1 in the
thickness ratio. Hence, the RV exhibits greater sensitivity sheep is about 1.2 to 1.3 : 1 in the humans.37,43,44 This ratio of
to changes in the afterload such as an increase in vascular the right to left ventricular outputs decreases with advancing 19
resistance, than the LV.40 Any increase in systemic arterial gestation, from 1.3 at 15 weeks to 1.1 at 40 weeks. This is due
http://vip.persianss.ir
1 Table 2
blood that is shunted through the FO.17 Oxygen saturations in
The combined cardiac output and its distribution in normal human different parts of the fetal circulation are shown in Figure 1.
fetuses during the second half of pregnancy42
Embryo to the Neonate
Fetal Circulation
At birth, after expansion of the lungs, there is a dramatic fall in
PVR and an 8 to 10 fold increase in pulmonary blood flow.15 Fetal Circulation in Congenital
The first breaths to inflate the lungs are thought to stimulate Heart Diseases25,53
pulmonary stretch receptors which mediate reflex dilatation
of the pulmonary vessels. Mechanical distention of the lungs Any development of a structural abnormality will modify the
also promotes local production of prostacyclin, a pulmonary fetal circulation. This will affect the development of other
artery vasodilator, further decreasing PVR. The improved components and can lead to other defects. The impact of the
oxygenation of the blood acts as a vasodilator both directly defect will depend on it’s severity and the time of gestation at
and through its ability to stimulate nitric oxide production.52 which it occurs. The fetal circulation is modified in many of the
The reduction in PVR leads to increase in pulmonary blood defects, but it will not significantly affect the fetal perfusion
flow and an increased venous return to the LA. and hence the fetal growth and development. This is because
As soon as the placenta is removed, there is a dramatic fall of the parallel fetal circulation and its connections at the atrial
in the flow through the DV and a significant fall in the venous and great arterial level. This allows adequate transport of
return through the IVC. The DV closes passively, 3 to 10 days blood to the placenta to pick up oxygen and deliver it to the
after birth. Thus, there is decrease in IVC flow, which results tissues. Thus, some CHDs are well-tolerated in utero, while
in a fall in venous return to the RA. This in turn means that others can result in severe compromise of the fetal circulation
less blood enters the RA causing right atrial pressures to fall. and early fetal death.
At the same time with an increase in pulmonary blood flow The fetal heart functions as a common mixing and pumping
due to the decrease in PVR, there is increase in the pulmonary chamber and hence many complex anomalies are compatible
venous return and subsequent elevation in LA pressures. with survival to term. Fetal shunt pathways play important
These two factors allow the pressures in the LA and RA to roles in the pathophysiology of many types of congenital
equalize. At this point the flap of the FO is pushed against the cardiac malformations. The defects associated with septal
atrial septum and the atrial shunt is effectively closed. This defects like atrial septal defect, ventricular septal defect (VSD)
initial ‘functional’ closure of the FO occurs within minutes rarely influence fetal cardiac development. In atrioventricular
to hours of birth. Anatomical closure occurs later via tissue septal defects, the obligatory flow from LV to RA will result
proliferation.15 in decrease in LV output and an increase in RV output. This
The shunt at the level of the DA becomes bidirectional will reduce the flow across the isthmus and can predispose to
with the reduction in the PVR. In addition, there is a dramatic coarctation. It is the degree of severity of the atrioventricular
reduction in the production of prostaglandin E2 (by the valve lesion and the regurgitation, which will determine the
placenta) and an increase in its metabolism (by the lungs).52 outcome.
This in combination with increased oxygen content in the Any interference with blood flow into or out of the LV or
blood provides the stimulus for the DA to constrict. The RV is known to interfere with its development. Premature
ductal tissue itself may become less sensitive to the dilating closure or restriction of the FO or mitral orifice results in LV
influences of the prostaglandins. Anything that increases the hypoplasia as a result of reduced blood flow, which decreases
PVR, such as acidosis, hypoxemia, polycythemia or lung the LV volume. In these fetuses with under development
disease, may keep the ductus patent. In healthy full term of the left side of the heart, the fetal RV and pulmonary
newborns, functional ductal closure occurs by 96 hours. artery are larger than usual reflecting flow redistribution.
This functional closure is followed by anatomical closure The compensatory dilation of the contralateral ventricle
via endothelial and fibrous tissue proliferation by 2 to 3 results in normalized CCO. In the fetus with mitral atresia
weeks.15,27 Once the DA closes, pulmonary artery pressures or aortic atresia, if the FO is sufficiently large and the
reduce significantly as the PVR decreases. The pulmonary DA accommodates the whole of the systemic blood flow,
artery pressures are approximately one-half of the aortic there will be no significant interference with intrauterine
pressures within the first 24 hours of life. Further decrease development and survival, but the problems will occur
in the PVR and involution of the pulmonary arteriolar after birth as the DA closes. Blood flows retrograde from
medial musculature occurs more gradually. The pulmonary the DA across the arch to the ascending aorta. The reduced
vasculature looks very similar to that of the adult by the age flow through the left heart in cases of atrioventricular valve
of 6 to 8 weeks.51 obstruction (atresia, stenosis) and in aortic atresia can result
Functional closure of the three shunts typically happens in in aortic hypoplasia and coarctation. The aortic isthmus is
the first 48 hours and is followed by tissue proliferation that especially vulnerable to small changes in intracardiac flow
results in anatomical closure and formation of the ligamentum from various congenital defects. This may account for the
arteriosus and ligamentum venosus, while fusion of the relatively high incidence of narrowing or atresia in this 21
http://vip.persianss.ir
1 region. The increased flow in the DA allows the substrate presence of the FO. Venous return is diverted away from the
for development of a posterior aortic wall ridge opposite ventricle with obstructed outflow and preferentially enters
the orifice and usually a narrowing results at this site. Other the ventricle with the greater diastolic compliance. In cases
Embryo to the Neonate
CHDs may be associated with decreased flow into the aorta of critical aortic valve stenosis, congestive heart failure can
thus interfering with its development. Thus in the fetus with occur with hydrops fetalis.
tricuspid atresia with transposition, the aorta arises from the In the fetus, TOF, total anomalous pulmonary venous
RV. If only a small VSD is present, the RV is small and flow connection (TAPVC) and transposition of great arteries (TGA)
into the ascending aorta is restricted, resulting in hypoplasia. are well-tolerated. In TOF, depending on the severity of the
Infants with aortic atresia have been reported to show a obstruction to the pulmonary blood flow, the aorta will carry a
high incidence of neurodevelopmental problems due to the larger percentage of CCO. Hence, there is a larger amount of
reduced cerebral blood flow during fetal life. blood flow across the ascending aorta and the isthmus and they
The patency of the fetal flow pathways is very important for tend to be larger. If the obstruction to the pulmonary blood
fetal survival when the right side of the heart is underdeveloped, flow is very severe, blood flow to the lungs will be supplied
as in absent right atrioventricular connection with right via the DA from the descending aorta (i.e. the reverse of the
ventricular hypoplasia or with severe right ventricular outflow normal situation). In absent pulmonary valve syndromes,
obstruction (RVOTO), as in critical pulmonary stenosis or pulmonary artery branches are greatly dilated. Significant
atresia. The size of the FO and the flow through it is larger pulmonary regurgitation can seriously affect perfusion of the
than normal. All the venous blood returning to the heart is pulmonary vessels and cause abnormal development of the
directed through the FO to the LA and hence the LV provides intrapulmonary vessels.
the total output of the heart. Thus, due to the decreased venous In the fetus, TAPVC, may be masked as the pulmonary
filling into the RV and increased flow and volume into the LV, venous return is already low. If whole of the pulmonary
the LV size is more than the RV. The DA is smaller in caliber venous return drains into the SVC, LV will be totally free
than normal and is usually more vertically oriented than in the of pulmonary venous blood and hence will be of higher
normal fetus. This is due to the smaller than normal volume saturation. LA and LV will be relatively small in TAPVC.
of flow across the DA and then into the branch pulmonary In TGA, the aorta arises from the RV and the pulmonary
arteries. Also, as the total CCO is ejected into the ascending artery from the LV. The FO and DA develop normally and
aorta, there is higher flow across the aortic isthmus. The hence there are no major circulatory consequences of this
ascending aorta is large and the aortic isthmus is as wide as lesion in utero. Restriction of the FO and the DA is more
the descending aorta. These changes are also observed with likely to be observed in later gestation. The diameter of the
other malformations that reduce right ventricular output, such DA will be reduced as a result of both the lower flow through
as tricuspid atresia and tetralogy of Fallot (TOF) with severe it and the constrictor effect of the higher oxygen saturation.
pulmonary stenosis. The increased pulmonary blood flow will result in greater
In a fetus with rapidly developing RVOTO with intact return of blood to the LA and this tends to reduce the size
ventricular septum, RV and LV cannot compensate and the CCO of the FO. The presence of these changes in the fetus is
falls. But if the RVOTO develops slowly, both LV and RV can predictive of early severe hypoxemia postnatally.
compensate and CCO is maintained. If severe RVOTO develops Congenital cardiovascular malformations with valvar
early in gestation in the fetus with intact ventricular septum, regurgitation most often cause elevation in the systemic
the DA flow is reversed and carries only 8 to 10 percent of the venous pressure. The regurgitant atrioventricular valves
cardiac output. The DA will be narrower and will make an acute can lead to chamber dilation, hydrops fetalis and death.
inferior angle with the aorta. The DA will remain patent for a Atrioventricular valve regurgitation is noted in many fetuses
longer duration than normal. In these fetuses with RVOTO with with Ebstein malformation, some with atrioventricular septal
intact ventricular septum, if significant tricuspid regurgitation defect and in pulmonary regurgitation with absent pulmonary
(TR) develops, RV pressure remains low and myocardial valve syndrome. Some fetuses with obstruction to the LV,
sinusoids and coronary fistula do not develop. But if TR does such as with aortic atresia or to the RV output, such as with
not develop, then there is significant RV systolic pressure and if DA constriction, may develop increased venous pressure. The
this occurs early in gestation there is development of coronary manifestation of the elevated venous pressure is fetal hydrops.
fistula and intramyocardial sinusoids. In the fetus with Ebstein’s anomaly, severe TR can manifest
In the fetus with isolated aortic or pulmonary stenosis as cardiac failure especially if the FO is restrictive. There
there is interference with the outflow of the left or right is marked enlargement of the RA and the atrialized RV can
ventricle respectively and this restricts the stroke volume of cause septal displacement and compromise the LV output.
the affected chamber. Ventricular muscle mass increases in Functional pulmonary atresia can result and ductal flow
response to the increased systolic pressure. The left or right may be reversed. Marked enlargement of the RA can cause
atrial pressure does not increase significantly because of the pulmonary hypoplasia.
22
Pathologic Fetal Ductus Arteriosus25,53 References 2
In normal fetal circulation, as a large volume is ejected by 1. Berhrsin J, Gibson A. Cardiovascular system adaptation at
Fetal Circulation
the RV, the pulmonary trunk is large and due to the direction birth. Paediatr Child Health. 2011;21:1-6.
of flow through the ductus, the inferior angle between the 2. Galen. Opera Omnia IV:243. In Dalton JC (translator):
ductus and the descending aorta is oblique. In the fetus with Doctrines of the Circulation. Philadelphia: Lea’s Sons and Co;
1884:68.
RVOTO obstruction, either stenosis or atresia, RV output is
3. Vesalius A. De Humani Corporis Fabrica Libri Septem. Ex Off.
markedly reduced. This results in poor development of the Ioannis Oporim, Basileae, 1543.
main pulmonary artery and the ductus. Hence, due to the 4. Spigel A. Adriani Spigelii Bruxellensis equitis D. Marci,
direction of flow in the ductus, it results in an acute inferior olim in patavino Gymnasio Anatomiae et Chirurgiae Profess.
angle of the ductus with the descending aorta. In LV outflow Primarij, De Humani Corporis Fabrica Libri Decem. Tabulis
obstruction, as in aortic atresia, the RV output is increased XCIIX aeri incisis elegantissimis, nee ante hac visis exornati,
and the blood flow through the DA is markedly increased. The screnissimo Ioanni Carnelio Venetiarum Duci Dicati. Opus
ductus is large and connects with the descending aorta with a posthumum. Daniel Bucretius Vratislaviensis Philos. et Medic.
wide oblique inferior angle. D. Jussu Authoris in lucem profert. Venetiis MDCXXVII.
5. Harvey W. Movement of the heart and blood in animals. Franklin
Constriction of the DA in the fetus increases the smooth
KJ (translator). Oxford: Blackwell Scientific Publishers, 1957.
muscle development, which results in elevation of the PVR. 6. Barclay AE, Barcroft J, Barron DH, et al. A radiographic
This may interfere with the normal fall in PVR after birth. demonstration of the circulation through the heart in the adult
Constriction of the DA in utero may result from administration and in the foetus, and the identification of the ductus arteriosus.
of non-steroidal anti-inflammatory agents (prostaglandin Br J Radiol. 1939;12:505-18.
inhibitors) to the mother. Acute ductal constriction, may be 7. Born GV, Dawes GS, Mott JC, et al. Changes in the heart
associated with acute right ventricular dilation and TR due to and lungs at birth. Cold Spring Harb Symp Quant Biol.
‘afterload mismatch’, which is reversible with discontinuation 1954;19:102-8.
of the offending agent. A similar response may occur with 8. Rudolph AM, Heymann MA. The circulation of the fetus in
utero. Methods for studying distribution of blood flow, cardiac
acutely increased impedance to the RV due to marked
output and organ blood flow. Circ Res. 1967;21:163-84.
placental insufficiency, relating to vascular disease within the 9. Rudolph AM, Heymann MA. Circulatory changes during
placental circuit. These changes may result in irreversible RV growth in the fetal lamb. Circ Res. 1970;26:289-99.
pump failure. 10. Rudolph AM. Fetal and neonatal pulmonary circulation. Ann
Rev Physiol. 1979;41:383-95.
Conclusion 11. Rudolph AM. The changes in the circulation at birth: Their
importance in congenital heart disease. Circulation. 1970;41:
Fetal circulation is uniquely adapted to the intrauterine life 343-59.
of low oxygen saturation and non-functional lungs. The 12. Winsberg F. Echocardiography of the fetal and newborn heart.
Invest Radiol. 1972;7:152-8.
fetal circulatory pathways facilitate placental gas exchange
13. Matsui H, Gardiner H. Current aspects of fetal cardiovascular
and promote distribution of oxygenated blood to the vital function. Fetal Matern Med Rev. 2008;19:61-84.
organs of the fetus. The preparation for postnatal adaptation 14. Rudolph AM. Distribution and regulation of blood flow in the
occurs throughout fetal life. The postnatal circulatory changes fetal and neonatal lamb. Circ Res. 1985;57:811-21.
influences the clinical presentation and clinical course of the 15. Murphy PJ. The fetal circulation. Continuing education in
neonate with CHD. Congenital cardiac malformations may anesthesia, intensive care and pain. 2005;5:107-12.
fundamentally alter the circulatory pattern of the human fetal 16. Kent B, Whitaker. Fetal Circulation. Comprehensive Perinatal
cardiovascular system. Fetal echocardiography has enhanced and Pediatric Respiratory Care. Delmar Thomson Learning;
the early diagnosis of CHDs. The progression of the disease 2001;18-20.
17. Kiserud T. Physiology of the fetal circulation. Semin Fetal
processes and the physiological events need to be studied in
Neonatal Med. 2005;10:493-503.
more detail in humans. There is a possibility that prenatal 18. Ellis H. Anatomy of fetal circulation. Anesthesia and intensive
intervention may alter the development of detrimental care medicine. 2005;6:73.
physiological phenomenon/events, thereby improving both 19. Kiserud T, Rasmussen S, Skulstad SM. Blood flow and degree
fetal and mature adult outcomes. of shunting through the ductus venosus in the human fetus. Am
J Obstet Gynecol. 2000;182:147-53.
Natural forces within us are the true healers of disease. 20. Bellotti M, Pennati G, De Gasperi C, et al. Role of ductus
—Hippocrates venosus in distribution of umbilical flow in human fetuses
23
http://vip.persianss.ir
1 during second half of pregnancy. Am J Physiol Heart Circ
Physiol. 2000;279:H1256-63.
37. Reed KL, Meijboom EJ, Sahn DJ, et al. Cardiac Doppler flow
velocities in human fetuses. Circulation. 1986;73:41-6.
21. Sharma A, Ford S, Calvert J. Adaptation for life: a review of 38. Gilbert RD. Control of fetal cardiac output during changes in
Embryo to the Neonate
neonatal physiology. Anaesthesia and intensive care medicine. blood volume. Am J Physiol. 1980;238:H80-H86.
2010;12:85-90. 39. Iwamoto HS. Cardiovascular effects of acute fetal hypoxia and
22. Szwast A, Rychik J. Current concepts in fetal cardiovascular asphyxia. In: Hanson MA, Spencer JAD, Rodeck CH (Eds). Fetus
disease. Clin Perinatol. 2005;32:857-75. and Neonate Physiology and Clinical Applications. 1. Circulation,
23. Barclay AE, Franklin KJ, Prichard MML. The foetal circulation vol. 1. Cambridge: Cambridge University Press, 1993.
and cardiovascular system and the change that they undergo at 40. Reller MD, Morton MJ, Reid DL, et al. Fetal lamb ventricles
birth. Oxford, Blackwell Scientific; 1944:275. respond differently to filling and arterial pressures and to in
24. Ho SY, Angelini A, Moscoso G. Developmental cardiac utero ventilation. Pediatr Res. 1987;22:621-6.
anatomy. In: Long WA (Ed). Fetal and Neonatal Cardiology. 41. Pinson CW, Morton MJ, Thornburg KL. Mild pressure
Philadelphia, WB Saunders Co; 1990:3-16. loading alters right ventricular function in sheep. Circ Res.
25. Rudolph AM. The fetal circulation. In: John Wiley and Sons. 1991;68:947-57.
Congenital Diseases of the Heart: Clinical-Physiological 42. Rasanen J, Wood DC, Weiner S, et al. Role of the pulmonary
Considerations. 3rd edition. UK; 2009. pp. 1-24. circulation in the distribution of human fetal cardiac output during
26. Schmidt KG, Silverman NH, Rudolph AM. Assessment of the second half of pregnancy. Circulation. 1996;94:1068-73.
flow events at the ductus venosus–inferior vena cava junction 43. De Smedt MCH, Visser GHA, Meijboom EJ. Fetal cardiac
and at the foramen ovale in fetal sheep by use of multimodal output estimated by Doppler echocardiography during mid and
ultrasound. Circulation. 1996;93:826-33. late gestation. Am J Cardiol. 1987;60:338-42.
27. Freed MD. Fetal and Transitional Circulation. In: Keane JF, 44. Sutton MG, Plappert T, Doubilet P. Relationship between
Lock JE, Fyler DC (Eds). Nadas’ Pediatric Cardiology. 2nd placental blood flow and combined ventricular output with
edition. Saunders, Pennsylvania; 2006:75-9. gestational age in normal human fetus. Cardiovasc Res.
28. Brace RA. Regulation of blood volume in utero. In: Hanson 1991;25:603-8.
MA, Spencer JAD, Rodeck CH (Eds). The circulation, Fetus 45. Rychik J. Fetal cardiovascular physiology. Pediatr Cardiol.
and neonate. Physiology and clinical application, Vol. 1. 2004;25:201-9.
Cambridge: Cambridge University Press; 1993. pp. 75-99. 46. Iwamoto HS, Kaufman T, Keil LC, et al. Responses to acute
29. Brace RA. Fetal blood volume response to intravenous saline hypoxemia in fetal sheep at 0.6-0.7 gestation. Am J Physiol.
solution and dextrane. Am J Obstet Gynecol. 1983;143:777- 1989;256:H613-20.
81. 47. Kiserud T, Jauniaux E, West D, et al. Circulatory responses to
30. Castle B, Mackenzie IZ. In vivo observations on intravascular acute maternal hyperoxaemia and hypoxaemia assessed non-
blood pressure in the fetus during mid-pregnancy. In: Rolfe invasively by ultrasound in fetal sheep at 0.3-0.5 gestation. Br
P, (Ed). Fetal physiological measurements. London, Boston, J Obstet Gynaecol. 2001;108: 359-64.
Durban, Singapore, Toronto, Wellington: Butterworths; 1986. 48. Reynolds SRM. Fetal and neonatal pulmonary vasculature in
pp. 65-9. guinea pig in relation to hemodynamic changes at birth. Amer
31. Johnson P, Maxwell DJ, Tynan MJ, et al. Intracardiac pressures J Anat. 1956;98:97-102.
in the human fetus. Heart. 2000;84:59-63. 49. Cassin S, Dawes GS, Mott JC, et al. The vascular resistance
32. Ville Y, Sideris I, Hecher K, et al. Umbilical venous pressure of the fetal newly ventilated lung of the lamb. J Physiol. 1964;
in normal, growth-retarded and anemic fetuses. Am J Obstet 171:61-79.
Gynecol. 1994;170:487-94. 50. Cook CD, Drinker PA, Jacobsen HN, et al. Control of pulmo-
33. Friedman WF. The intrinsic physiologic properties of the nary blood flow in the fetal and newly born lamb. J Physiol.
developing heart. Prog Cardiovasc Dis. 1972;15:87-111. 1963;169:10-29.
34. Thornburg KL, Morton MJ. Development of the cardiovascular 51. Rao PS. Perinatal circulatory physiology: Its Influence on
system. In: Thorburn GD, Harding R, (Eds). Textbook of fetal clinical manifestations of neonatal heart disease. Neonatology
physiology. Oxford: Oxford University Press; 1994. Today. 2008;3:6-12.
35. Artman M. Sarcolemmal sodium–calcium exchange activity 52. Zeltser I, Tabbutt S. Critical Heart Disease in the Newborn. In
and exchanger immunoreactivity in developing rabbit hearts. Pediatric Cardiology: The Requisites in Pediatric Cardiology.
Am J Physiol. 1992;263:H1506-H1513. Vetter VL (Ed). Mosby, Inc, US; 2006. pp. 31-3.
36. Grant DA, Fauche`re JC, Eede KJ, et al. Left ventricular stroke 53. Rudolph AM. Congenital cardiovascular malformations and
volume in the fetal sheep is limited by extracardiac constraint the fetal circulation. Arch Dis Child Fetal Neonatal (Ed).
and arterial pressure. J Physiol. 2001;535:231-9. 2010;95:F132-6.
24
C hapter
Etiopathogenesis of
3 Congenital Heart Diseases
Krishnamoorthy KM
http://vip.persianss.ir
1 structures of the fetus. The cells are severely damaged, includes CHD ranging from ventricular and atrial septal
becoming swollen and vacuolated and sometimes destroyed. defects to complex conotruncal defects.21 Extensive review
Most offsprings (90%) have ‘flow’ defects, especially patent on this association is available.22
Embryo to the Neonate
Narcotics Clomiphene
Case-control studies29 reported an association of CHD in Maternal use of clomiphene was associated with coarctation of
offsprings with maternal codeine use during the first trimester the aorta and tetralogy of Fallot.8 Among 397 newborns from
of pregnancy, but with methodological limitations. Other women treated with clomiphene in a study, four had ventricular
studies failed to confirm this.42 septal defects.60 This was more than expected and the rate of
all CHD was significantly high. Atrial and ventricular septal
Sympathomimetics defects, as well as coarctation of aorta were observed in
another study.61 The same authors published their observations
There are conflicting reports of association of phenylephrine on the incidence of CHD among women, who conceived
with CHD: a case-control study with positive association43 after assisted reproductive technology.62 Studies that have
and a large cohort study with negative association.41 investigated the impact of clomiphene on fetal development
have been criticized for combining the use of clomiphene with
Corticosteroids assisted reproductive technology. In fact, the defect categories
that appear to be associated with both clomiphene and assisted
A similar conflicting data is available for the association reproductive technology are similar: septal heart defects and
of maternal corticosteroid use and CHD. The Baltimore- esophageal atresia.61,62 Further, the small number of cases,
Washington Infant Study showed a possible association by inconsistency of some findings with previous reports and the
univariate analysis, but not when other variables were taken inability to assess the clomiphene effect separately from that of
into account.44 infertility alert to a cautious interpretation.
http://vip.persianss.ir
1 chemotherapy for cancer in childhood, found CHD in 10 mellitus does not affect the risk of malformation in the fetus.
percent of such children.63 However, the duration of diabetes has a significant effect on
the malformation risk with higher incidence seen in infants of
Embryo to the Neonate
Non-therapeutic Drug Exposure mothers with a longer duration of diabetes. Paternal diabetes
does not increase the risk. These observations suggest that
maternal diabetes, through its adverse effects on maternal
Cocaine and Marijuana
metabolism, is the responsible factor for the increase of
Maternal: A case report suggested that single ventricle may malformations in the fetus.
result from maternal cocaine ingestion.64 Coronary occlusion
in the developing fetal heart due to coronary spasm could have Early Lesions
produced an infarct, which destroyed the right ventricle. This
fetal pathology may be one mechanism that leads to single The pattern of CHD encountered with an emphasis on
ventricle hearts. Data from a case-control study, the Atlanta abnormalities of laterality, looping and conotruncal septation
Birth Defects Case-Control Study, investigated the role of suggests that maternal diabetes affects cardiogenesis very early,
maternal cocaine ingestion in the induction of single ventricles prior to 7 weeks of gestation.73,74 Experimental embryogenesis
and found no association.65 In this study, even if maternal in a medium with high glucose concentrations, shows that the
cocaine ingestion during pregnancy was a purported cause of migratory and proliferative capacity of neural crest cells are
single ventricle, most cases appeared to be unrelated to this affected.75 ‘Early onset’ defects like conotruncal anomalies
exposure. An increased frequency of CHD was seen among are thus explained in diabetic pregnancies. The case of two
infants with neonatal toxicology screens showing the prevalence infants of diabetic mothers, with DiGeorge syndrome and
of cocaine in 1 study, with peripheral pulmonic stenosis as the normal chromosome 22q11, further illustrates that maternal
leading diagnosis and in far greater numbers than in the general diabetes may be a pathogenic factor in this anomaly.76 In the
population.66 Case-control studies have reported an association Baltimore-Washington Infant Study, only the ‘early’ CHD
of maternal cocaine abuse with increased risk of any CHD,67 (defects of primary cardiogenesis) were strongly associated
heterotaxy68 and membranous ventricular septal defects.8 with maternal diabetes, while those arising later in cardiac
Paternal: The Baltimore-Washington Infant Study reported development (obstructive and shunting defects in four-
an association of paternal cocaine use with an increased risk chambered hearts) were not significantly associated.77
of any CHD and with ventricular septal defects and tricuspid
atresia in particular.8 In this study, it was found that paternal Mechanism
marijuana use and use of cocaine among older fathers were
risk factors for isolated membranous ventricular septal defects It is believed that the abnormal glucose levels disrupt expression
in offspring.69 The evaluation of these drugs is hampered due of a regulatory gene in the embryo, leading to embryotoxic
to the concomitant use of tobacco and alcohol and therefore apoptotic cellular changes.78 Variations in glucose metabolism
individual effect is difficult to evaluate. In the Atlanta Birth and/or protein glycosylation, perhaps of genetic origin, affect
Defects Case-Control Study, risk of isolated simple ventricular the vascular complications of diabetes.79 Vascular alterations
septal defects doubled in offsprings with maternal self- and as a common pathway to cardiovascular maldevelopment
paternal-proxy reported marijuana use.70 Risk of isolated might be initiated by aneuploidy and by maternal diabetes.
simple ventricular septal defect increased with regular Both of these etiological factors would explain the occurrence
(3 day/week) marijuana use for both maternal self- and of early, rather than late CHD. Another postulated mechanism
paternal-proxy report. The association was significant for is an association between excess oxygen radical activity and
maternal self-report. Maternal use of marijuana was also disturbed embryogenesis in diabetic pregnancy.80 Adminis
found to be associated with a slight increase in risk for Ebstein tration of antioxidants to diabetic pregnant rodents can reduce
anomaly in the Baltimore-Washington Infant Study.8 the risk for diabetes-associated embryopathy.81 A higher
genetic susceptibility towards congenital malformations also
Parental medical conditions plays a role in diabetic women.82 Pregestational diabetes
increases the risk of CHD83 and is hypothesized to change the
Among CHD, 1 percent of CHD can be attributed to maternal expression of a regulatory gene important for the septation of
diseases, such as type I diabetes and phenylketonuria.42 the outlet tract of the heart.84
http://vip.persianss.ir
1 of neonates with CHD were compared with normal neonates exposed to the toxins. Both maternal and paternal exposure
in one study.104 More mothers of neonates with CHD smoked to toxins increased the CHD risk in children, who carried the
(40.8% vs 19.7%) during pregnancy. Logistic regression combined null GST genotypes. Polymorphisms in GST genes
Embryo to the Neonate
analysis showed that periconceptional tobacco smoking can modify a person’s risk of toxicant exposure. It showed
was associated with increased risk of CHD in the offspring. that GST polymorphism might mediate the risks of parental
Incidence of neonatal CHD increased with the level of fetal exposure to toxin for CHD.
tobacco exposure, suggesting a dose effect too. Genetic polymorphisms in the nitric oxide synthase (NOS)
gene are associated with birth defects. In a population-based
Quantification registry, single nucleotide polymorphisms in the NOS3 gene
among infants with conotruncal defects were more likely to
Any-time smokers have babies with septal defects, the associ- carry the variant alleles for NOS3 (922A > G), NOS3 (298G
ation being stronger for mothers, who reported heavier tobac- > T) or both and to have mothers who smoked cigarettes
co consumption during pregnancy.105 This was independent periconceptionally compared with control infants.112 The
of potential confounding factors. Mothers, who smoked > 25 gene-environment interaction reported by this study illustrates
cigarettes/day more often gave birth to babies with right-sided the importance of the associations among CHD, maternal
obstructive lesions.105 The dose-effect relation for CHD was exposure and genetic variants that modify the effect of
confirmed in a case-control study.104 Maternal overweight and exposure on developing hearts.
smoking may have a synergistic adverse effect on the devel-
opment of the fetal heart and these women should be strongly Paternal
encouraged to stop smoking and to lose weight before becom-
ing pregnant.106 Father’s cigarette smoking has been shown to be more common
among children with ventricular septal defect.113 Other studies
Mechanism showed that parental smoking, particularly when both parents
were smokers, increased the risk of conotruncal defects.114
Smoking during pregnancy results in deposition of tobacco It is also believed that male exposure might exert a
constituents in the circulation of mother and hence the teratogenic effect through toxic nicotine compounds adsorbed
fetus. This serves as serious hazard at all stages of human to the sperm and transmitted to a woman in the ejaculate. The
development.98 Gestational smoking results in placental contaminant is absorbed by the woman, where it might reach
pathologies, preterm birth, low birth weight and structural and adversely affect a current pregnancy or may even remain
malformations in the offspring, abnormal somatic growth in the woman’s body to influence future pregnancies.108
and increased blood pressure in childhood.98 Nicotine and In all these studies, some residual confounding could
carbon monoxide have high placental permeability, resulting not be excluded. Exposure to environmental smoking was
in increased concentrations in the fetal circulation compared determined by maternal self-reports, without independent
to maternal levels.98 Nicotine constricts the uterine arteries, biochemical validation.
reducing placental blood flow.107 Carbon monoxide increases
fetal carboxyhemoglobin impairing fetal oxygenation.98 Both Parental alcohol intake
contribute to tobacco-associated fetal hypoxia, which exerts a
teratogenic effect.
Maternal
Environmental toxin can induce oxidative deoxyribonucleic
acid (DNA) damage, mutations and chromosomal aberrations, Alcohol abuse is known to be teratogenic and among the effects
such as DNA strand breaks and aneuploidy.108 They might act seen are CHD.115 Some studies could not find an association.33
in human seminal fluid as endocrine disrupting agents causing Ethanol produces fetal tissue edema and affects the turgor of
direct germ line DNA damage or epigenetic changes.108 the primitive cardiac loop. Alcohol intake is associated with
Smoking is associated with increased oxidative stress,109 increased oxidative stress109 that decreases the activity of
which can decrease the functional activity of methionine methionine synthase through limiting the availability of reduced
synthase through limiting the availability of reduced vitamin vitamin B12. Homocysteine and S-adenosylhomocysteine
B12. As mentioned in the section on alcohol, homocysteine are elevated. S-adenosylhomocysteine is a potent product
accumulates and produces its toxic effects.110 inhibitor of cellular methyltransferases, which during
Glutathione S-transferase (GST) polymorphisms were organogenesis can alter gene expression, cell differentiation
investigated in a study on mothers of affected children and apoptosis.110 Homocysteine has embryotoxic effect and
with CHD.111 The modification effect of susceptibility in leads to inhibition of DNA methyltransferase reactions, DNA
children, who lacked the genetic capacity to produce GSTM1 hypomethylation and altered gene expression.
and GSTT1 enzymes was explored. Paternal smoking The first description of fetal alcohol syndrome pointed
30 (>15 cigarettes/day) was found to be associated with CHD at alcohol, as a cardiac teratogen.116 Atrial, ventricular and
risk. An additive risk was present, when both parents were conotruncal defects are predominantly seen after maternal
alcohol consumption during pregnancy.117 In a case-control In a review125 of all major randomized trials and 3
study of patients with conotruncal abnormalities and observational studies from 1992 to 2000, three studies121-123
ventricular septal defects, the effect of maternal alcohol use showed an overall decrease in the risk of CHD in the range
http://vip.persianss.ir
1 Vitamin A Washington Infant Study, maternal exposure to herbicides and
rodenticides were linked to an increased risk of transposition
The association between high vitamin A in the diet and/or of the great arteries and maternal exposure to pesticides with
Embryo to the Neonate
supplements and neural crest cell defects (cardiac and non- total anomalous pulmonary venous return and membranous
cardiac defects) or outflow tract have been addressed in some ventricular septal defects.8 A recent case-control study
studies. An increased risk of CHD with an intake of more of various end-product uses reported an increased risk of
than 10,000 IU retinol in the form of supplements129,130 and conotruncal defects with maternal exposure to insecticides.132
occurrence of defects of the cardiac outflow tract at dosages The Baltimore-Washington Infant Study, a case-control
more than 18,000 to 25,000 IU/day in animals have been study of CHD in liveborn infants, revealed an association
described. of maternal exposure to herbicides and rodenticides during
the first trimester with transposition of great arteries in their
environmental factors infants.138 Regarding the dose-response relation, it was found
that the risk was sequentially increased when mothers, who
reported one-time exposures and mothers reporting monthly
Organic Solvents
exposures were each compared with unexposed mothers. One
Maternal occupational exposure to organic solvents, chemicals, study has shown no association of maternal pesticide exposure
dyes and paints is a signifcant risk factor for CHD and specifically at work places with a risk for CHD.136
for ventricular septal defects.54,55,131 The Baltimore-Washington
Infant Study showed that maternal exposure to degreasing or other Air Quality
solvents was associated with an increased risk of hypoplastic
left heart syndrome, coarctation of the aorta, pulmonic stenosis, Studies have addressed the associations of ambient air
transposition of the great arteries with intact ventricular pollutants with CHD. A population-based case-control
septum, tetralogy of Fallot, total anomalous pulmonary venous study139 looked at risks of CHD associated with second
return, non-chromosomal atrioventricular septal defects and trimester exposure to carbon monoxide, sulfur dioxide,
Ebstein anomaly.8 Other associations are that of occupational nitrogen dioxide, ozone and particulate matter less than 10 µm
exposure to organic solvents and increased risk of ventricular in aerodynamic diameter. There were associations between:
septal defects;118,132 dyes, lacquers and paints with conotruncal 1. Carbon monoxide exposure and increased risk of
malformations;133 and mineral oil products with coarctation of ventricular septal defect and tetralogy of Fallot,
the aorta.134 Genetic susceptibility to the effects of solvents and 2. Ozone exposure and elevated risk of aortic artery and valve
paints has been suggested.135 Genetic polymorphisms in key defects, pulmonary artery and valve defects and conotruncal
solvent-metabolizing enzymes, glutathione S-transferases, were defects,
found to mediate the risks of solvents and paints for pulmonic 3. Particulate matter less than 10 µm in aerodynamic diameter
valve stenosis and atrial septal defect. and atrial septal defect,
4. Sulfur dioxide and ventricular septal defects.
Chemicals at Workplaces The difference is explained by the usage of a different
critical window of exposure in the analysis: gestational month-
Hazardous maternal occupation has been implicated in the specific exposures140 vs mean exposure for the entire period
causation of CHD in some studies.54 A study investigated the of susceptibility, from gestational weeks 3 through 8.139
possible associations between CHD and maternal occupational
exposure to various factors during the first trimester of Groundwater Contamination
pregnancy.136 The cases were taken from infants diagnosed with
CHD, while controls were randomly selected from all normal Contamination of public drinking water supplies by
births during the same period. Maternal overall exposure to chlorinated hydrocarbon solvents reportedly was associated
chemicals at work was more prevalent among the case group. with increased risks for CHD.141–143 The risk of CHD was
Among the specific chemical groups, maternal exposure to greater among children of parents, who had contact with areas
dyes, lacquers or paints was significantly associated with the that had groundwater contaminated with trichloroethylene
risk of CHD. Exposure to organic solvents during the first than among children of parents, who had no such contact.141
trimester increased the risk of ventricular septal defects. Work Another study after evaluating the actual maternal
at video display terminals was more prevalent among the consumption of home tap water during the first trimester of
case group. pregnancy found an increased risk of CHD.142
http://vip.persianss.ir
1 Bad Obstetric History recurrences of CHD in families
This is associated with an increased risk of tetralogy of Fallot, Family History as Risk Factor
Embryo to the Neonate
http://vip.persianss.ir
1 and non-genetic environmental factors play crucial roles in It requires fewer study subjects, since affected persons can
this. It is believed that CHD is caused by the interaction of be ascertained from a few sources; it is also more cost-
genetic and environmental factors182,183 and 30 percent of effective. Most of the data on risk factors come from case-
Embryo to the Neonate
some CHD may be attributable to identifiable and potentially control studies and the best available information comes from
modifiable factors.46 After a teratogenic insult, fetuses may be two large population-based case-control studies specifically
unaffected, suggesting that only a subpopulation may be at risk. designed to investigate risk factors for CHD in an exploratory
In contrast, several syndromic and familial cases of CHD are manner. The Baltimore-Washington Infant Study conducted
caused by rare single-gene mutations that have major effects. in the Baltimore-Washington area between 1981 and 19898
The predisposition to CHD involves multiple factors, and the study conducted in Finland by the National Public
including different genetic loci, epigenetic factors (e.g. Heath Institute in Helsinki of cases and controls born during
DNA methylation or histone modifications that affect gene 1982 to 1984.131 These larger, population-based studies used
expression), environmental influences, subtle hemodynamic standardized methods for ascertaining and classifying CHD
factors during cardiac development or a combination of these and methods to minimize potential biases.
factors. The common forms of CHD that appear to be sporadic
may be caused by inherited genetic variants that affect protein Limitations of the Studies
expression or function and manifest, as disease only when
combined with additional genetic, epigenetic, environmental The disadvantages of case-control studies are the potential
or hemodynamic insults.128 A parent may harbor a genetic for selection bias in assembling the case population, such that
predisposition to a disease (susceptibility allele) and transmit the cases are not representative of all the patients with the
this genetic risk to the offspring. However, this would result disease. This bias may relate to non-participation in the study
in CHD only in conjunction with variants in other genetic loci or to incomplete participation and missing information on the
or with epigenetic factors, resulting in disease penetrance. exposure questions. It is possible that women, who conceive
The susceptibility allele alone may not be sufficient to cause after exposure are more likely to participate in the study.
disease in offspring (non-penetrance), but the individual Further, some studies focus on individuals with severe CHD,
would still be at risk for vertical transmission of increased some include all types of CHD.
risk. A potential disease-susceptibility allele could lead to Then there is the potential for recall bias. Maternal
disease penetrance or non-penetrance, depending on the size recollection of periconceptional events may be influenced by
of the effect of the susceptibility allele and the presence of the birth of a child with a congenital malformation, calling to
‘second hits’ that modify the phenotype. mind events and exposures suspected as being teratogenic.
In the Baltimore-Washington Infant Study, significant Assessment is based on parental recall after the birth of the child.
associations were found for membranous ventricular septal Most studies on non-genetic factors in the etiopathogenesis of
defects with paternal marijuana use, cocaine use among CHD suffer from recall and interviewer bias. They are based
older fathers and African-American race of the infant. These on retrospective interview data or questionnaires. This could
associations support a multifactorial etiologic hypothesis for very often be long after the birth of the infant. This method
isolated membranous ventricular septal defects.69 of data collection may carry the risk for recall bias and
when interviews are part of routine birth defect registration,
Studies on risk factors for CHD interviewer bias can also be involved.
Patients with more severe CHD may not survive to
While etiopathogenesis of CHD has been comprehensively adulthood or their handicap prevents them from having a
reviewed, it may be noted that there are controversies child. Individuals with a milder defect might be included
and conflicts too. Hence, it is appropriate to look into the more often in such studies. If more severe CHD are associated
methodology of collection of data in the various studies with a higher risk to the offspring, the estimated relative
described. risk could be underestimated. Some CHD may have subtle
symptoms or, for better or worse, be asymptomatic. Some
Study Designs are strongly age-dependent in manifestations, following the
natural history of the malformation. Some CHD (e.g. small
The ideal study design for the epidemiological approach ventricular septal defects) spontaneously resolve and are not
to CHD is a randomized clinical trial. Except for prenatal diagnosed. There is no universal coding or nomenclature
multivitamin supplements containing folic acid, which system, hampering communication among scientists.
reduce the occurrence of CHD,121,123 there are very few Further, CHD is not a single disease, but rather a spectrum
preventive strategies. Then there are case-control studies. encompassing many specific diagnoses, each of which may
They identify patients with CHD, select a comparison group be distinct in origin and risk factors. Many fetuses with CHD
and retrospectively evaluate the risk factors in the two groups. die in utero, resulting in a survival bias among the types of
36
CHD present among live births. Technological advances might be due to confounding by the condition for which the 3
in diagnosis (e.g. echocardiography) have increased the analgesic was taken (e.g. influenza or a febrile illness) and
sensitivity of diagnosis, which makes it difficult to compare the apparent protective effect of multivitamin supplement use
http://vip.persianss.ir
1 12. Zhang J, Cai WW. Association of the common cold in the
first trimester of pregnancy with birth defects. Pediatrics.
33. Bossi L. Fetal effects of anticonvulsants. In: Morselli PL,
Pippenger CE, Penry JK (Eds). Antiepileptic drug therapy in
1993;92:559-63. pediatrics. New York (NY): Raven Press; 1983. pp.37-64.
Embryo to the Neonate
13. Chambers CD, Johnson KA, Dick LM, et al. Maternal fever 34. Bracken MB. Drug use in pregnancy and congenital heart
and birth outcome: a prospective study. Teratology. 1998; 58: disease in offspring [Letter]. N Engl J Med. 1986;314:1120.
251-7. 35. Pursley TJ, Blomquist IK, Abraham J, et al. Fluconazole-
14. Shaw GM, Nelson V, Carmichael SL, et al. Maternal induced congenital anomalies in three infants. Clin Infect Dis.
periconceptional vitamins: interactions with selected factors 1996; 22:336-40.
and congenital anomalies? Epidemiology. 2002; 13:625-30. 36. Moore JA. An assessment of lithium using the IEHR
15. Nilsen NO. Endothelial changes and microvascular leakage Evaluative Process for Assessing Human Developmental and
due to hyperthermia in chick embryos. Virchows Arch B Cell Reproductive Toxicity of Agents: IEHR Expert Scientific
Pathol Incl Mol Pathol. 1984; 46:165-74. Committee. Reprod Toxicol. 1995; 9:175-210.
16. Nilsen NO. Vascular abnormalities due to hyperthermia in 37. Llewellyn A, Stowe ZN, Strader JR Jr. The use of lithium and
chick embryos. Teratology. 1984; 30:237-51. management of women with bipolar disorder during pregnancy
17. Mirkes PE, Cornel LM, Park HW, et al. Induction of and lactation. J Clin Psychiatry. 1998;59(suppl 6):57-64.
thermotolerance in early post-implantation rat embryos is 38. Weinstein MR. Lithium treatment of women during
associated with increased resistance to hyperthermia-induced pregnancy and in the post-delivery period. In: Johnson N
apoptosis. Teratology. 1997; 56:210-9. (Ed). Handbook of Lithium Therapy. Lancaster, Pa: MTP
18. Roulston A, Marcellus RC, Branton PE. Viruses and apoptosis. Press. 1980. pp.421-9.
Ann Rev Microbiol. 1999; 53:577-628. 39. Warner JP. Evidence-based psychopharmacology, 3: assessing
19. Watanabe M, Choudhry A, Berlan M, et al. Developmental evidenceof harm: what are the teratogenic effects of lithium
remodeling and shortening of the cardiac outflow tract in- carbonate? J Psychopharmacol. 2000; 14:77-80.
volves myocyte programmed cell death. Development. 1998; 40. Jacobson SJ, Ceolin L, Kaur P, et al. Prospective multicentre
125:3809-20. study of pregnancy outcome after lithium exposure during first
20. Taussig HB. A study of the German outbreak of phocomelia.The trimester. Lancet. 1992; 339:530-3.
thalidomide syndrome. J Am Med Assoc. 1962;180:1106-14. 41. Heinonen OP, Slone D, Shapiro S. Birth defects and drugs in
21. Smithells RW, Newman CG. Recognition of thalidomide pregnancy. Littleton, Mass: Publishing Sciences Group Inc;
defects. J Med Genet. 1992; 29:716-23. 1977.
22. Lenz W. A short history of thalidomide embryopathy. 42. Shaw GM, Malcoe LH, Swan SH, et al. Congenital cardiac
Teratology. 1988; 38:203-15. anomalies relative to selected maternal exposures and conditions
23. Hernandez-Diaz S, Werler MM, Walker AM, et al. Folic acid during early pregnancy. Eur J Epidemiol. 1992; 8:757-60.
antagonists during pregnancy and the risk of birth defects. N 43. Rothman KJ, Fyler DC, Goldblatt A, et al. Exogenous
Engl J Med. 2000; 343:1608-14. hormones and other drug exposures of children with congenital
24. Czeizel AE, Rockenbauer M, Sorensen HT, et al. The heart disease. Am J Epidemiol. 1979; 109:433-9.
teratogenic risk of trimethoprim-sulfonamides: a population 44. Ferencz C, Rubin JD, McCarter RJ, et al. Congenital heart
based case-control study. Reprod Toxicol. 2001; 15:637-46. disease: prevalence at livebirth: the Baltimore-Washington
25. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid Infant Study. Am J Epidemiol. 1985; 121:31-6.
embryopathy. N Engl J Med. 1985; 313:837-41. 45. Ericson A, Kallen BA. Nonsteroidal anti-inflammatory drugs
26. Botto LD, Loffredo CA, Scanlon KS, et al. Cardiac outflow in early pregnancy. Reprod Toxicol. 2001; 15:371-5.
tract defects in the offspring of mothers who took retinol 46. Wilson PD, Loffredo CA, Correa-Villasenor A, et al.
supplements. Proc Greenwood Genet Center. 1997; 16:146-7. Attributable fraction for cardiac malformations. Am J
27. Lynberg MC, Khoury MJ, Lammer EJ, et al. Sensitivity, speci- Epidemiol. 1998; 148:414-23.
ficity, and positive predictive value of multiple malformations 47. Ostensen M. Nonsteroidal anti-inflammatory drugs during
in isotretinoin embryopathy surveillance. Teratology. 1990; pregnancy. Scand J Rheumatol Suppl. 1998; 107:128-32.
42:513-9. 48. Lione A, Scialli AR. The developmental toxicity of
28. Dai WS, Hsu MA, Itri LM. Safety of pregnancy after discon- indomethacin and sulindac. Reprod Toxicol. 1995; 9:7-20.
tinuation of isotretinoin. Arch Dermatol. 1989; 125:362-5. 49. Norton ME. Teratogen update: fetal effects of indomethacin
29. Zierler S, Rothman KJ. Congenital heart disease in relation to administration during pregnancy. Teratology. 1997; 56:282-92.
maternal use of Bendectin and other drugs in early pregnancy. 50. Souter D, Harding J, McCowan L, et al. Antenatal indomethacin:
N Engl J Med. 1985; 313:347-52. adverse fetal effects confirmed. Aust N Z J Obstet Gynaecol.
30. Ardinger HH, Atkin JF, Blackston RD, et al. Verification of the 1998; 38:11-6.
fetal valproate syndrome phenotype. Am J Med Genet. 1988; 51. Hammerman C, Glaser J, Kaplan M, et al. Indomethacin
29:171-85. tocolysis increases postnatal patent ductus arteriosus severity.
31. Kozma C. Valproic acid embryopathy: report of two siblings Pediatrics. 1998; 102:E56.
with further expansion of the phenotypic abnormalities 52. Wilkinson AR. Naproxen levels in preterm infants after
and a review of the literature. Am J Med Genet. 2001; 98: maternal treatment. Lancet. 1980; 2:591-2.
168-75. 53. Zenker M, Klinge J, Kruger C, et al. Severe pulmonary
32. Cedergren MI, Selbing AJ, Källén BA. Risk factors for hypertension in a neonate caused by premature closure of the
cardiovascular malformation: A study based on prospectively ductus arteriosus following maternal treatment with diclofenac:
38
collected data. Scand J Work Environ Health. 2002; 28:12-7. a case report. J Perinat Med. 1998; 26:231-4.
54. Bassili A, Mokhtar SA, Dabous NI, et al. Risk factors
for congenital heart diseases in Alexandria, Egypt. Eur J
75. Siman CM, Gittenberger-De Groot AC, Wisse B, et al.
Malformations in offspring of diabetic rats: morphometric
3
Epidemiol. 2000; 16:805-14. analysis of neural crest-derived organs and effects of maternal
http://vip.persianss.ir
1 93. Watkins ML, Botto LD. Maternal prepregnancy weight and
congenital heart defects in offspring. Epidemiology. 2001; 12:
polymorphisms, and congenital heart disease. Am J Cardiol.
2011; 108:1625-31.
439-46. 112. Shaw GM, Iovannisci DM, Yang W, et al. Risks of human
Embryo to the Neonate
94. Mikhail LN, Walker CK, Mittendorf R. Association between conotruncal heart defects associated with 32 single nucleotide
maternal obesity and fetal cardiac malformations in African polymorphisms of selected cardiovascular disease-related
Americans. J Am Med Assoc. 2002; 94:695-700. genes. Am J Med Genet. 2005; 138:21-6.
95. Queisser-Luft A, Kieninger-Baum D, Menger H, et al. Does 113. Savitz DA, Schwingl PJ, Keels MA. Influence of paternal age,
maternal obesity increase the risk of fetal abnormalities? smoking, and alcohol consumption on congenital anomalies.
Analysis of 20 248 newborn infants of the Mainz Birth Register Teratology. 1991; 44:429-40.
for detecting congenital abnormalities. Ultraschall Med. 1998; 114. Wasserman CR, Shaw GM, O’Malley CD, et al. Parental
19:40-4. cigarette smoking and risk for congenital anomalies of the
96. Waller DK, Mills JL, Simpson JL, et al. Are obese women at heart, neural tube, or limb. Teratology. 1996; 53:261-7.
higher risk for producing malformed offspring? Am J Obstet 115. Alpert JJ, Zuckerman B. Alcohol use during pregnancy: what
Gynecol. 1994; 170:541-8. is the risk? Pediatr Rev. 1991; 12:375-9.
97. Nora JJ, Nora AH. Recurrence risks in children having one 116. Clarren SK, Smith DW. The fetal alcohol syndrome. N Engl J
parent with a congenital heart disease. Circulation. 1976; 53: Med. 1978; 298:1063-7.
701-2. 117. Carmichael SL, Shaw GM, Yang W, et al. Maternal
98. Rogers JM. Tobacco and pregnancy: overview of exposures periconceptional alcohol consumption and risk for conotruncal
and effects. Birth Defects Res C Embryo Today. 2008; 84(1): heart defects. Birth Defects Res Part A Clin Mol Teratol. 2003;
1-15. 67:875-78.
99. Kallen K. Maternal smoking and congenital heart defects. Eur 118. Tikkanen J, Heinonen OP. Risk factors for ventricular septal
J Epidemiol. 1999; 15:731-7. defect in Finland. Public Health. 1991; 105:99-112.
100. Torfs CP, Christianson RE. Maternal risk factors and 119. Martinez-Frias ML, Bermejo E, Rodriguez-Pinilla E, et al. Risk
major associated defects in infants with Down syndrome. for congenital anomalies associated with different sporadic and
Epidemiology 1999; 10:264-70. daily doses of alcohol consumption during pregnancy: a case-
101. Woods SE, Raju U. Maternal smoking and the risk of congenital control study. Birth Defects Res A Clin Mol Teratol. 2004;
birth defects: a cohort study. J Am Board Fam Pract 2001; 70:194-200.
14:330-4. 120. Tikkanen J, Heinonen OP. Risk factors for atrial septal defect.
102. Hobbs CA, James SJ, Jernigan S, et al. Congenital heart Eur J Epidemiol. 1992; 8:509-15.
defects, maternal homocysteine, smoking, and the 677 CNT 121. Czeizel AE. Periconceptional folic acid containing multivi-
polymorphism in methylenetetrahydrofolate reductase gene: tamin supplementation. Eur J Obstet Gynecol Reprod Biol.
evaluating gene–environmental interactions. Am J Obstet 1998; 78:151-61.
Gynecol. 2006; 194:218-24. 122. Botto LD, Mulinare J, Erickson JD. Occurrence of congenital
103. Steinberger EK, Ferencz C, Loffredo CA. Infants with heart defects in relation to maternal mulitivitamin use. Am J
single ventricle:a population-based epidemiological study. Epidemiol. 2000; 151:878-84.
Teratology. 2002; 65:106-15. 123. Shaw GM, O’Malley CD, Wasserman CR, et al. Maternal
104. Karatza AA, Giannakopoulos I, Dassios TG, et al. Periconcep- periconceptional use of multivitamins and reduced risk
tional tobacco smoking and isolated congenital heart defects in for conotruncal heart defects and limb deficiencies among
the neonatal period. Int J Cardiol. 2011; 148:295-9. offspring. Am J Med Genet. 1995; 59:536-45.
105. Malik S, Cleves MA, Honein MA, et al. National Birth Defects 124. Scanlon KS, Ferencz C, Loffredo CA, et al. Preconceptional
Prevention Study; National Birth Defects Prevention Study. folate intake and malformations of the cardiac outflow tract.
Maternal smoking and congenital heart defects. Pediatrics. Epidemiology. 1998; 9:95-8.
2008; 121:e810-e6. 125. Botto LD, Olney RS, Erickson JD. Vitamin supplements and
106. Baardman ME, Kerstjens-Frederikse WS, Corpeleijn E, et al. the risk for congenital anomalies other than neural tube defects.
Combined adverse effects of maternal smoking and high body Am J Med Genet. 2004; 125C:12-21.
mass index on heart development in offspring: evidence for 126. Junker R, Kotthoff S, Vielhaber H, et al. Infant methylenetet-
interaction? Heart. 2012; 98:474-9. rahydrofolate reductase 677TT genotype is a risk factor for
107. Shi M, Wehby GL, Murray JC. Review on genetic variants and congenital heart disease. Cardiovasc Res. 2001; 51:251-4.
maternal smoking in the etiology of oral clefts and other birth 127. Wenstrom KD, Johanning GL, Johnston KE, et al. Association
defects. Birth Defects Res C: Embryo Today. 2008; 84:16-29. of the C677T methylenetetrahydrofolate reductase mutation
108. Gianicolo EA, Cresci M, Ait-Ali L, et al. Smoking and and elevated homocysteine levels with congenital cardiac
congenital heart disease: the epidemiological and biological malformations. Am J Obstet Gynecol. 2001; 184:806-12.
link. Curr Pharm Des. 2010; 16:2572-7. 128. Shieh JTC, Srivastava D. Heart Malformation. What Are the
109. Moller P, Wallin H, Knudsen LE. Oxidative stress associated Chances It Could Happen Again? Circulation. 2009; 120:269-
with exercise, psychological stress and life-style factors. Chem 71.
Biol Interact. 1996; 102:17-36. 129. Rothman KJ, Moore LL, Singer MR, et al. Teratogenicity of
110. Hobbs CA, Cleves MA, Melnyk S, et al. Congenital heart high vitamin A intake. N Engl J Med. 1995; 333:1369-73.
defects and abnormal maternal biomarkers of methionine and 130. Botto LD, Loffredo C, Scanlon KS, et al. Vitamin A and cardiac
homocysteine metabolism. Am J Clin Nutr. 2005; 81:147-53. outflow tract defects. Epidemiology. 2001; 12:491-6.
40
111. Cresci M, Foffa I, Ait-Ali L, et al. Maternal and paternal 131. Tikkanen J, Heinonen OP. Risk factors for cardiovascular
environmental risk factors, metabolizing GSTM1 and GSTT1 malformations in Finland. Eur J Epidemiol. 1990; 6:348-56.
132. Shaw GM, Nelson V, Iovannisci DM, et al. Maternal occupa-
tional chemical exposures and biotransformation genotypes as
152. Maron BJ, Applefeld JM, Krovetz LJ. Racial frequencies in
congenital heart disease. Circulation. 1973; 47:359-61.
3
risk factors for selected congenital anomalies. Am J Epidemiol. 153. Carmichael SL, Shaw GM. Maternal life event stress and
http://vip.persianss.ir
1 173. Gatrad AR, Read AP, Watson GH. Consanguinity and complex
cardiac anomalies with situs ambiguus. Arch Dis Child. 1984;
cytoplasmic inheritance and vulnerability to teratogens. Am J
Cardiol. 1987; 59:459-63.
59:242-5. 179. Connolly HM, Warnes CA. Ebstein’s anomaly: outcome of
Embryo to the Neonate
174. Becker SM, Al Halees Z, Molina C, et al. Inbreeding and pregnancy. J Am Coll Cardiol. 1994:23:1194-8.
congenital heart disease in Saudi Arabia. Am J Med Genet. 2001; 180. Emanuel R, Somerville J, Inns A, et al. Evidence of congenital
99:8-13. heart disease in the offspring of parents with atrioventricular
175. Yunis K, Mumtaz G, Bitar F, et al. Consanguineous marriage defect. Br Heart J. 1983; 49:144-7.
and congenital heart defects: A case-control study in the 181. Nora J, Nora AH. Update on counselling the family with a
neonatal period. Am J Med Genet A. 2006; 140:1524-30. first degree relative with a congenital heart defect. Am J Med
176. Gev D, Roguin N, Freundlich E. Consanguinity and congenital Genet. 1988:29:137-42.
heart disease in the rural Arab population in northern Israel. 182. Nora JJ. Multifactorial inheritance hypothesis for the etiology
Human Heredity. 1986; 36:213-7. of congenital heart diseases: the genetic-environmental
177. Jain VK, Nalini P, Chandra R, et al. Congenital malformations, interaction. Circulation. 1968; 38:604-17.
reproductive wastage and consanguineous mating. Aust NZ J 183. Ferencz C, Correa-Villasenor A. Epidemiology of cardiovascular
Obst Gynaecol. 1993; 33:33-6. malformations: the state of the art. Cardiol Young. 1991; 1:264-84.
178. Nora J, Nora AH. Maternal transmission of congenital heart 184. Miettinen OS, Reiner ML, Nadas AS. Seasonal incidence of
disease. New recurrence risk figures and the questions of coarctation of the aorta. Br Heart J. 1970; 32:103-07.
42
C hapter
4 Fetal Cardiology
Shardha Srinivasan
eOver the past two decades, rapid advances in the field of planning of pregnancy and delivery options and institution of
ultrasound, in conjunction with developments in surgery, appropriate fetal and neonatal management strategies.
invasive cardiology and intensive care has revolutionized
the field of pediatric cardiology. With this came the need IdentIFyIng the Fetus at rIsk For
for early diagnosis of congenital heart disease (CHD) in an CongenItal heart dIsease
effort to further improve morbidity and mortality. Ultrasound
has been increasingly applied to the evaluation of the fetal The incidence of congenital cardiac malformations in
cardiovascular system allowing for more detailed evaluation newborns is approximately 5 to 11/1,000 live births.1–5
of cardiac structure as well as its function. Over the past decade CHDs are 8 times more common than Down syndrome for
or so, fetal cardiology has evolved into a highly specialized which there are currently well-established prenatal screening
field, based on close collaboration between perinatology and protocols. Recent studies suggest that the overall incidence has
pediatric cardiology. been stable over the past decade.2,6 CHD may be attributed to
Ultrasound provides a unique ability for noninvasive various different etiologies, which can be stratified into three
assessment of fetal heart and cardiovascular system including: groups: fetal, maternal and familial risks as outlined in Table
1. The assessment of fetal cardiac anatomy and its alterations 1. However, there are currently no strong markers for fetal
2. The assessment of fetal cardiovascular physiology CHD with the highest yield being in the setting of abnormal
3. Assessment of fetal rhythm. cardiac screening views in 42 to 69 percent, followed by fetal
Advances in transducer technology and ultrasound machines chromosomal abnormalities in 47 to 50 percent and presence
and the resultant improvement in image resolution allows of other extracardiac abnormalities in 4.4 to 9 percent.7,8 A
for evaluation of anatomic details at much greater level and diagnosis of CHD is established in about 2.7 to 20 percent of
prenatal detection of most CHD. Early assessment of fetal heart cases referred for a fetal echocardiogram.8,9
and serial assessments have provided us with an understanding Maternal metabolic disorders such as pregestational diabetes
of the evolution of certain types of lesions; spurring the and phenylketonuria are associated with heart defects in fetus.
exploration of interventional strategies in some lesions in an Though a 3 to 5 times increase in risk for CHD is reported in
attempt to modify the evolution to more significant heart disease. maternal diabetes, recent data suggests that this higher risk is
Doppler evaluation of the fetal heart and fetal cardiovascular associated with poor control and higher hemoglobin A1c levels
system has provided us with unique insights into cardiovascular in the periconceptional period. Recent studies have reported
physiology and fetal compensatory mechanisms to both altered yields of 0 to 7 percent and are likely reflective of the setting
structure as well as in the setting of noncardiac pathologies and in which the study is performed.8,9 Other maternal risk factors
the pathophysiology of fetal heart failure. Ultrasound has also include exposure to either drugs or viral infections (Table 1)
contributed significantly to our ability to diagnose, monitor and that may damage the developing heart with resultant CHD and
manage fetal arrhythmias. Fetal echocardiography now has a myocarditis. Fetal dilated cardiomyopathy has been reported
significant role in the management of not just fetal CHD, but with maternal viral infections.10,11 Maternal autoantibodies
also in several noncardiac fetal pathologies. especially anti-Ro and anti-La antibodies can cross the placenta
Prenatal diagnosis of CHD allows for evaluation of between 16 to 18 weeks gestation with a risk for fetal heart
associated genetic or noncardiac lesions that can impact block and cardiomyopathy in about 1 to 3 percent cases, but
outcomes, better counseling and preparation of the family, the majority of these occur in asymptomatic women.
http://vip.persianss.ir
1 table 1
Indications for fetal echocardiography
Embryo to thE NEoNatE
Fetal chromosomal abnormalities have a high association Abnormalities with a particular association with CHD are
with underlying congenital heart defects. 3,12 These include included in Table 1. CHD may rarely present with either
cases of trisomy 21, 13 and 18 and 22q11 deletion. An significant tachycardia or bradycardia in the setting of
elevated first trimester nuchal translucency (NT) is a marker complex congenital heart defects, though overall incidence is
for aneuploidy and in the setting of normal chromosomes for low. Recent publications indicate a higher risk for CHD in
other fetal malformations including CHD.13 In the study by conditions such as twin-twin transfusion syndrome (TTTS) and
Hyett et al the prevalence of major CHD increased with an in vitro assisted conceptions.21–23 Fetal echocardiograms are
increase in the NT, from 0.8 per 1000 live births for a NT also increasingly being used for assessment of cardiovascular
less than 95 percentile to 63.5 per 1000 live births for those status and function in noncardiac lesions such as TTTS as well
with a NT greater than 99 percentile or about 3.5 mm and 55 as conditions associated with altered loading conditions on
percent of cases with CHD had an elevated NT between 10 the heart such as vascular tumors, diaphragmatic hernia and
to14 weeks gestation.13 However, the diagnostic accuracy of congenital cystic adenomatoid malformation (CCAM).
increased NT as a predictor of CHD in the general population A family history of CHD remains an important indication
has been lower. Based on a meta-analysis, Makrydimas et al for fetal echocardiography not because of high yields, but for
concluded that approximately 30 percent of the major CHD the reassurance that a normal study provides to these families.
detected by specialist echocardiography in a chromosomally Single gene disorders such as microdeletion of chromosome
normal population, had a NT greater than 99 percentile, 22 (del 22q 11) have been associated with patterns of CHD
but sensitivity has been lower in other population based typically involving the conotruncus. Recurrence risks are
studies.14–17 Nonetheless, the prevalence of CHD is 3 to 4 higher for certain lesions such as heterotaxy syndromes and
folds higher in the fetus with a NT greater than 3.5 mm and it left heart obstructive lesions.24,25
serves as an important indication for fetal echocardiography. The majority of CHD occurs in the absence of clearly
Other markers such as abnormal ductus venosus flow patterns identifiable risk factors and ideally all pregnancies should
in very early pregnancy as well as the presence of tricuspid be screened for heart defects in conjunction with the
regurgitation in early gestation are being explored as potential midgestation anomaly scan.9,26–28 There are many published
markers for CHD.18–20 studies and commentaries outlining the wide variation in
Fetuses with extracardiac malformations merit a complete prenatal pickup of CHD variably attributable to differences
cardiac evaluation. Malformations in more than one in scanning protocol-4 chamber alone versus inclusion of
44 system may indicate a syndrome or chromosomal anomaly. outflow tract imaging, instrumentation and level of training
of sonographers.27,29–33 Inclusion of outflow tracts improves limitations of image resolution are particularly important in 4
detection of conotruncal lesions, which have a high likelihood these early scans and it is important to keep use of color and
of being ductal dependent.28,34 Improvement in pickup rates pulsed Doppler to the minimum necessary. Given potential
FEtal Cardiology
with regional training programs is well-demonstrated in for evolution of certain lesions through gestation, it remains
several European countries.35,36 However, recent studies necessary to perform a follow-up scan between 24 to 28 weeks
continue to demonstrate a wide variability in referral patterns in these cases. Currently, these early scans are mostly limited
for fetal echocardiography as well as pick up of cardiac to select population at high-risk such as those with abnormal
abnormalities on routine scanning.30,31,37 Table 2 outlines the first trimester screening or where the reassurance is important
anticipated abnormality by different views. as in a family history for CHD.
table 2
Expected findings on screening images in different congenital heart diseases
http://vip.persianss.ir
1 To achieve the above requirements a balance between evaluation of Fetal Position and right-left orientation
penetration and the maximal possible lateral resolution is
needed. Most current ultrasound machines used for fetal It is critical that all fetal cardiac assessments begin with
Embryo to thE NEoNatE
imaging provide transducers with a range of imaging evaluating fetal position and establishing fetal right versus
frequencies, with typical frequencies used being the 4 to 10 left. Once the fetal stomach is identified as being correctly
MHz range. Lower frequencies along with use of harmonic positioned to the fetal left, it then serves as a useful landmark
imaging may be needed in the setting of increased fetal depth to reorient oneself through the scan with fetal movements.
or poor insonation characteristics. Linear array transducers Though there are algorithms that have been outlined for the
or phased array transducers with dynamic focus may be same,46 the easiest method is to establish fetal lie and thus the
used. Postprocessing should be set to improve frame rates by fetal left and right. This is best done by identifying the fetal
judicious use of dynamic zoom and optimal depth with low head and aligning the transducer along the spine of the fetus
persistence and spatial averaging. Endocardial definition is to establish the craniocaudal axis of the fetus and then turning
enhanced by the use of relatively high dynamic contrast and the transducer 90 percent to obtain a transverse scan through
appropriate grayscale map. Use of color flow mapping tends the abdomen and thorax.
to drop frame rates and it is especially important to set a small
region of interest and optimize color scales. Finally, given transverse scans and the extended
the dynamic nature of the heart, the capacity to record and Cardiac screening Views
display real time images along with still frames of Doppler
and M-mode recordings, is critically important. A series of transverse scans starting from the upper abdomen
Four dimensional evaluation using spatiotemporal image to ascertain situs, to the chest outlining the four chambers of
correlation (STIC) technology is now possible. Inherent the fetal heart and then to the mediastinum visualizing the
limitations are imposed by the temporal resolution and motion outflow tracts and great vessels, provides for a comprehensive
artifact. With the inclusion of color flow information good screening technique (Figure 1). Initially advocated by Yagel
diagnostic accuracy for detection of major CHD has been et al, this provides a template for sequential segmental
demonstrated.41–44 The ability to analyze the data set offline, evaluation of cardiac anatomy as noted in Figure 2.47 It should
may have an important impact on improving accessibility of be noted that these imaging planes represent a continuum and
cardiac screening to remote sites. As with other techniques small movements separate one view from the other.
there is a learning curve to the process and often a 1. Abdominal situs: The transverse scan across the upper
combination of techniques and postprocessing is required abdomen of the fetus helps to establish the abdominal situs.
to achieve good diagnostic capability. Fetal movements and Normal landmarks (Figure 1: plane A and Figure 3A)
arrhythmia continue to be issues. Inter and intraobserver include:
variability approaching 96 percent has been demonstrated for • Spine posterior
the assessment of fetal cardiac volumes.45 • Stomach bubble to left
• Pulsatile descending aorta anterior to spine, slightly left
normal Fetal echocardiogram of midline
• Inferior vena cava slightly anterior to right of descending
It is important to evaluate the fetal heart in a segmental aorta
fashion with the goal towards establishing situs, segmental • Scanning cranially the cardiac mass is noted with apex
connections and alignments as well as functional assessment to left
(Figures 1 and 2). Fetal position, as well as motion may not • The inferior vena cava passes anteriorly to drain into the
allow for these to be assessed in a sequential fashion as in base of right atrium.
postnatal studies; hence, it is important to have a mental Besides this, the umbilical vein is noted looping
or written checklist to make sure that all components are away from the stomach and the ductus venosus can be
understood at the end of the study. Poor visualization or identified as a small vessel connecting the umbilical vein
incomplete visualization should prompt a repeat study. to the inferior vena cava. Color flow evaluation shows low
Scanning the fetal heart requires small controlled movements. velocity accelerated continuous flow pattern.
The importance of assessment in a segmental fashion as Alterations in abdominal situs or right/left symmetry
well as assessment of morphologic characteristics of various may be the first clue to associated heterotaxy. The presence
cardiac structures cannot be stressed enough; especially in of a prominent venous structure posterior to the aorta may
the diagnosis of congenital heart defects where in seemingly be seen in setting of interruption of the inferior vena cava
minor issues may alter prognosis and surgical approach, such with either an azygos continuation (right posterior vessel)
as associated obstructed total anomalous pulmonary venous (Figure 3B) or hemiazygos continuation (left posterior
return. vessel). In these cases, the flow in the vein is cephalic,
46
4
FEtal Cardiology
E d
a
Figure 1: Schema for extended cardiac screening. A series of
transverse scans through the fetal chest and upper abdomen constitutes
the extended cardiac screening as advocated by Yagel et al. Plane A
is through the upper abdomen of the fetus showing abdominal situs.
Scanning cephalic one gets the four chamber view in Plane B, the left
ventricular outflow tract in Plane C, right ventricular outflow tract and
three vessel view in Plane D and the three vessel tracheal view in Plane E.
AA = Aortic arch; DA= Ductal arch; LVOT = Left ventricular outflow tract;
RV = Right ventricle; RVOT = Right ventricular outflow tract; S =
Spine; St = Stomach; T = Trachea. Note: It is a very small movement
between planes C, D and E
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b
Figures 3a and b: Transverse scan through the upper abdomen: A. Normal situs: The fetus was in breech position with stomach (St) to the left
and cardiac mass (not shown) was to the left. Normal relation of the aorta (solid white arrow) and IVC is noted; B. Interruption of the IVC with
azygos continuation. In this case there was isolated dextrocardia with the cardiac apex pointing to the right (not shown). A prominent azygos
vein is noted as a venous structure, posterior and to the right of the descending aorta (solid while arrow). IVC = Inferior vena cava; LT = Fetal
left; S = Spine; St = Stomach.
Landmarks include: Early in gestation there is relative equality of the two sides
• Spine is posterior though there may be mild right sided prominence past
• Descending aorta is noted anterior to spine and slightly 28 – 30 weeks’ gestation and this becomes more prominent
to left of midline in late gestation. The four chamber view may be projected
• Anteriorly, the cardiac mass lies with apex to left and either horizontally or vertically depending on the angle
occupies about a third of the chest of imaging. The perimembranous septum is normally the
• Cardiac axis of about 45 degrees to the line bisecting the thinnest part of the interventricular septum and is prone
thorax to dropout on two dimensional imaging. In these cases,
• Four chambers with a intact crux in the center: right = assessing the septum in a horizontal orientation to maximize
left (in midgestation) lateral resolution of the transducer and use of color flow
• Right atrium is anterior and receives the superior and mapping will help resolve the issue (Figure 4B). However,
inferior vena cava given relatively equal pressures between the two ventricles
• Left atrium is posterior and receives the pulmonary and the limitations of resolution may result in missed
veins (The space between the left atrium and aorta is diagnosis of a ventricular septal defect (VSD), especially in
free of vascular structures at this level) early scans and with poor imaging windows. Abnormalities
• Foramen flap towards the left atrium in cardiac position may be noted in setting of extracardiac
• Right ventricle is anterior and is identified by the malformations with cardiac displacement, heterotaxy with
tricuspid valve and presence of moderator band at the or without associated cardiac displacement. A change in
apex cardiac axis is an important marker for associated cardiac
• Tricuspid valve is slightly offset towards the apex and defects as well as extracardiac malformations with resultant
has septal attachments cardiac shift. The differential features and common causes
• Left ventricle is posterior and receives the mitral valve are outlined in Table 3.
• Mitral valve is septophobic or lacks attachments to the 3. Outflow tract view: Scanning cephalic or towards the
septum and attaches slightly higher than the tricuspid fetal head from the four chamber view shows the origin of
valve the aorta from the left ventricle (Figure 1: Plane C). Slight
• Normal valve motion rotation of the transducer in such a way as to ‘lengthen’ the
• Normal myocardial squeeze and echogenicity interventricular septum will result in opening of the left
• Normal heart rate with atrioventricular synchrony ventricular outflow tract (LVOT) and better visualization
• Additional evaluation includes color flow and Doppler of the aortic valve (Figures 5A to C). Note is made of the
48 evaluation of the valves and septum. following:
4
FEtal Cardiology
a b
Figures 4a and b: Normal four chamber view of the heart: A. 2D image: The heart occupies about a third of the chest and the interventricular
septum forms about a 45° angle with the line bisecting the thorax. The right ventricle (RV) is the anterior ventricle and is identified by the
moderator band in the apex and apical offset of the tricuspid valve. ‘<’ marks the crux of the heart with an intact and normal offset of the
atrioventricular valves noted. The pulmonary veins (PV) (arrows) and foramen flap are related to the left atrium; B. HD-flow demonstrates flow
in the pulmonary veins (arrows) and the interventricular septum is intact. The right and left heart are approximately equal in size in both cases.
LT = Fetal left; RT = Fetal right
a b C
Figures 5a to C: Left ventricular outflow tract views: A. Normal heart: the aorta arises from the left ventricle and there is septoaortic continuity
(arrow) and the interventricular septum is aligned to the anterior wall of the aorta. There is also aortomitral continuity; B. The aorta arises
normally from the left ventricle but there is lack of septoaortic continuity (arrow) and color flow confirmed a subaortic ventricular septal defect
(not shown); C. In this case there is lack of septoaortic continuity (arrow) and in addition the aorta straddles the ventricular septum and is more
aligned to the right ventricle in setting of a malalignment ventricular septal defect. Ao = Aorta; LT = Fetal left; RT = Fetal right
• Aorta arises from the left ventricle and is situated in the 4. The 3 vessel view (3VV) and the 3 tracheal view (3VT):
center of the heart Extending the scan further cranially into the mediastinum
• Aortomitral continuity is present of the fetus demonstrates the three vessel view and its
• Aortoseptal continuity is present continuation into the tracheal view. This view outlines the
• Interventricular septum appears intact great vessels and their relationship in the mediastinum.
• Cranial scanning opens the pulmonary valve and These are easily obtained by a slow cranial sweep from
pulmonary artery the four chamber view (Figure 1: Plane D and E). A slight
• Normal valve motion is noted rotation of the transducer will help lay out the vessels.
• Color and Doppler evaluation is performed. 49
http://vip.persianss.ir
1 table 3
Variations in cardiac position and axis: distinguishing features and common causes
Embryo to thE NEoNatE
Dextroposition • All of cardias mass in right thorax • ↑ Mass in LEFT thorax with extrinsic
• Apex to front/left push: e.g. Left DH, left pleural effusion,
• Cardiac size often small CCAM
• ↓ Mass in right thorax: Right
lung agenesis or hypoplasia with
compensatory increase in left lung
Levoposition • All of cardiac mass in left thorax • ↑ Mass in RIGHT thorax with extrinsic
• Apex to front push: e.g. DH, pleural effusion, CCAM
• Cardiac size often small • ↓ Mass in left thorax: Left lung agenesis
or hypoplasia
Left axis shift • Majority of cardiac mass in left thorax • Shift of ventricular septum:
• Axis > 60° to midline Right ventricular enlargement/
• Cardiac size: Normal or enlarged hypertrophy
• Apex to left Left ventricular hypoplasia
• Milder forms of extrinsic shift
Right axis shift • Majority of cardiac mass in left thorax • Shift of ventricular septum:
• Axis < 30° to midline Right ventricular hypoplasia
• Size normal or increased Left ventricular enlargement
• Apex left or midline • Milder forms of extrinsic shift
50
CCAM = Congenital cystic adenomatoid malformation; CHAOS = Congenital high airway obstruction; DH = Diaphragmatic hernia
Landmarks include: abnormalities in number, size, alignment and flow in the 4
• Cranial sweep from the left outflow view opens the components of each of the views (Figures 6 and 7).
pulmonary valve and pulmonary artery
FEtal Cardiology
• Pulmonary valve is anterior and connects to the right sagittal Planes
ventricle
• Pulmonary artery gives off lateral branches 1. Aortic and ductal arch view: Scanning in the thorax
• There is a subpulmonary conus or muscle and lack of along the long axis or parallel to the spine provides the
continuity with the tricuspid valve sagittal images of the fetal heart. Due to the shadowing
• The two great arteries cross each other with the effects for the spine it is important to approach the heart
pulmonary valve being anterior and to the left of the slightly from the one side of the fetal spine. This window
aorta profiles the superior vena cava-inferior vena cava (SVC-
• The three vessels are seen from right to left: The right IVC) view, identifying the great veins as they enter the
superior vena cava, the ascending aorta and the main right atrium. Aortic arch forms a ‘candy cane’ with cranial
pulmonary artery head and neck vessels while the ductal arch is much more
• Ascending order in size with: The superior vena cava ≤ ‘shallow’ reminiscent of the American ‘hockey stick’
ascending aorta ≤ main pulmonary artery. (Figures 8A and B). Given embryologic origins the aortic
Scanning cephalic from here gives the tracheal view arch is slightly cranial to the ductal arch, though in cases
(Figure 1: Plane E): of severe arch hypoplasia this may be difficult to reliably
• Pulmonary artery continues into the ductal arch demonstrate. The right pulmonary artery can be seen
• Aorta continues to the aortic arch posterior to the ascending aorta and superior vena cava
• The aortic arch is slightly cephalic to the ductal arch (Figures 8A and 9A). The foramen ovale is well-profiled in
• The ductal arch and aortic arch come together to form a this view (Figure 9A). In the abdomen, the ductus venosus
‘V’ with apex at the descending aorta can be identified as it connects to the IVC in the liver.
• Three vessels are seen from right to left with ascending Short-axis images of the ventricles can be obtained and
order in size: The right superior vena cava ≤ the aortic the ventricular function and mitral valve papillary muscles
arch ≤ the ductal arch identified (Figure 9B).
• Trachea is noted slightly posteriorly between the 2. Short-axis images: Given horizontal positioning of the fetal
superior vena cava (SVC) and the aortic arch heart short-axis images of the ventricles can be obtained
• Further, cephalic innominate vein is noted crossing either from a relative fronto/sagittal position or from a
from left to right to join the SVC. transverse scan plane orthogonal to the four chamber view
Abnormalities in the 3 VV and 3 VT are important clues depending on fetal position. The mitral valve, papillary
for the presence of underlying conotruncal malformations muscles, function, pulmonary valve, branch pulmonary
and variations in arch anatomy. It is important to assess for arteries and the ductal arch are well seen.
a b C
Figures 6a to C: Three vessel view demonstrating normal right ventricular outflow tract and variations in size. A cross-section through
the fetal thorax demonstrating from fetal left-to-right—cross-section of the main pulmonary artery (PA), ascending aorta (Ao) and superior
vena cava (SVC). The branch pulmonary arteries are noted (arrow heads) arising from the PA in each case. A. Normal 3 vessel view.
Note: Gradually increasing size from SVC to Ao to PA and normal arrangement in a line; B. Dilated PA in a fetus with valvular pulmonary stenosis.
The ascending aorta is normal in size; C. Diminutive main PA with small confluent branch pulmonary arteries in setting of pulmonary atresia. 51
Lt = Fetal left; S = Spine.
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b
C d
Figures 7a to d: Three vessel tracheal view: A and B. Demonstrate normal three vessel tracheal view in the upper mediastinum of the fetus in
2D and with color flow mapping. Vessels from fetal right to left are superior vena cava (SVC); aortic arch (AA); ductal arch (DA). Note: The ‘V’
formed by the DA and the AA as they come together at the descending aorta to the left of the trachea (T). The direction of flow should be similar
in the two arches; C and D. The AA is noted to the right of the trachea while the DA passes to the left of the trachea and thus the ‘V’ is disrupted
in this fetus with a right AA
a b
Figures 8a and b: Normal sagittal views of the fetal arches: A. Aortic arch (*) demonstrating a candy cane with presence of cranial directed
52 head and neck vessels (arrow). Note: Right pulmonary artery (RPA) posterior to the ascending aorta. This view also profiles the foramen
ovale (FO). Descending aorta runs parallel to the spine (S); B. Demonstrates the pulmonary artery arising from the right ventricle (RV) and the
ductal arch (*) which is shallow and lacks the head and neck vessels. The aortic valve (AV) is seen in cross-section in the middle of the heart.
4
FEtal Cardiology
a b
Figures 9a and b: Normal sagittal short-axis image of the heart: A. Profiling the superior vena cava (SVC) and the sinus venosus atrial septum.
The foramen ovale (FO) is well profiled with the primum atrial septum bulging into the left atrium. The right pulmonary artery (RPA) is related to
the posterior aspect of the SVC. The inferior vena cava can be seen as it enters the right atrium from the abdomen but is not well profiled in the
current image; B. Extending the scan into the ventricles provides a sagittal short-axis image of the ventricles and profiles the mitral valve (MV)
and papillary muscles. Note: The stomach (St) is related to the left ventricle in this view. RV = RIght ventricle; S = Spine
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b C
d E F
Figures 10a to F: Fetus with critical aortic stenosis and dysplastic mitral valve: A. Four chamber image shows a massively dilated left atrium
(LA) and an enlarged left ventricle. The right heart appears smaller and “squished”; B. Sagittal image showing retrograde filling of the aortic
arch. Note: Good-sized left ventricle; C. Color and pulsed wave Doppler demonstrated severe mitral regurgitation; D. Mitral stenosis; E. The
foramen ovale demonstrated continuous high velocity flow (in this case left to right flow) consistent with restriction; F. The tricuspid valve shows
a monophasic filling pattern, likely to be secondary to restriction to right ventricular filling secondary to altered septal geometry
one ventricle), common inlet (common atrioventricular b. Discordant: Right ventricle to aorta and left ventricle
valve aligned to one ventricle) or single inlet (atresia of to pulmonary artery or transposed. As noted, this will
one valve either the mitral or tricuspid valve). result in a parallel orientation to the great vessels on
It is important to look carefully at the atrioventricular ultrasound (Figures 12A and B).
valves for presence of straddling attachments, which c. Double outlet: Where in the majority of both great
may change surgical management towards a single vessels arise from one ventricle, more commonly an
ventricle approach even though there are two effective anatomic right ventricle.
ventricles. Similarly, the size of the inflow may have a d. Single outlet: Where in there is only one outlet from the
significant impact on surgical approach. For example, ventricular mass. These include aortic atresia (small aorta
a small tricuspid valve annulus that is well below -3 Z and large pulmonary artery) and pulmonary atresia (small
scores may rule out a two ventricle repair even in the pulmonary artery and normal aorta) and a single large
presence of an otherwise reasonable sized right ventricle outlet as in cases of truncus arteriosus where in a single
in setting of severe pulmonary stenosis/atresia with an large outflow vessel gives rise to the coronaries, head
intact septum. and neck vessels as well as pulmonary arteries. A wide
3. Ventriculoarterial (VA) connections: variation in size and morphology of the atretic valve can be
a. Concordant: Normal, i.e. right ventricle to pulmonary seen and in some cases may hamper distinction between a
artery and left ventricle to aorta. true truncus and tetralogy of Fallot with pulmonary atresia.
In the normal heart, the great arteries cross each other Careful attention to the origin and relationships of the
and their relationship is such that visualization of one pulmonary arteries and head, neck vessels from the single
great artery in long axis will show a cross sectional view vessel is needed to make the diagnosis in these cases, to
of the other. The ability to show the long axis of both great help plan surgical intervention and outline prognosis.
54 arteries at the same time or parallel orientation of great Ultimately, the impact of complex heart defects depends on
vessels suggests abnormal connections and/or alignment. the ability of the fetus to tolerate the hemodynamic alterations
4
FEtal Cardiology
a b
C d
E F
g h
i
Figures 11a to i: Doppler profiles across different sites in the fetal cardiovascular system: A. Atrioventricular valves demonstrate a biphasic flow
pattern. ‘E’ wave corresponds to passive filling during early diastole and ‘A’ wave to augmented filling with atrial systole; B. Ductus arteriosus
and aortic arch show systolic forward flow with low velocity forward flow in diastole; C. Hepatic veins and inferior vena cave demonstrate a low
velocity bimodal forward flow pattern. ‘S’ wave corresponds to annular motion with ventricular systole, diastolic (D) forward flow with ventricular
filling and a transient ‘A’ reversal wave is noted with atrial contraction; D. The main pulmonary artery and aorta show systolic forward flow pattern;
E. Normal ductus venosus flow also demonstrates these three components except that forward flow is maintained during atrial systole and
presents as a decrease in velocity rather than ‘A’ reversal. F. The proximity of the branch pulmonary artery and pulmonary vein allows for
simultaneous sampling of the two. High resistance forward flow pattern is noted in the branch pulmonary artery (PA) and is shown above
the baseline in F with pulmonary venous flow below the baseline; G. The umbilical vein (UV) shows continuous low velocity forward flow.
The umbilical artery (UA) demonstrates pulsatile flow with a systolic peak with continuous forward flow in diastole. With increasing placental
resistance there is a gradual decrease in diastolic flow velocity in the UA; H. The middle cerebral artery also shows a systolic peak with low
velocity forward flow into diastole. Conditions associated with cerebral vasodilatation will result in higher diastolic velocities; I. The foramen ovale
shows predominantly low velocity flow from the right atrium (RA) to the left atrium (LA) with a transient flow reversal
55
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b
Figures 12a and b: Parallel orientation of the great vessels in setting of D-transposition of the great vessels.
The pulmonary artery arises from the left ventricle and the aorta from the anterior right ventricle
a b C
Figures 13a to C: A. Four chamber view demonstrating a dilated coronary sinus (CS). The interventricular septum appears intact in this view;
B. Outflow tract view demonstrating origin of the aorta (Ao) and lack of septo-aortic continuity secondary to a large subaortic ventricular septal
defect (arrow head); C. Three vessel tracheal view demonstrating presence of four vessels: right superior vena cava (RSVC); aorta (Ao);
pulmonary artery (PA); left superior vena cava (LSVC); trachea (T). The LSVC can also be visualized as a vessel to the left of the pulmonary
artery in B
sPeCIFIC lesIons
in utero and its ability to have a successful transition to neonatal
circulation. In the fetal circulation, the right and left hearts are 1. Systemic venous abnormalities: Variations in systemic
working in parallel rather than in series as after birth. There venous anomalies can be easily detected on fetal
exists the potential for flow redistribution across the foramen echocardiograms. A dilated coronary sinus is often the clue
ovale as well as ductus arteriosus. Obstruction or resistance to look for an associated left superior vena cava (LSVC).
to flow through one ventricle allows for redistribution of flow The presence of a LSVC can be easily confirmed in the high
across the foramen and the ductus arteriosus to the other. mediastinal or 3 VV and tracheal views by the presence of a
Hence, right heart obstruction or high afterload states on the fourth vessel leftward to the pulmonary artery (Figure 13).
left ventricle may present with relative enlargement of the Though this variation has no hemodynamic significance,
right ventricle and vice versa. Similarly, one may see flow it is often noted as an associated finding in left heart
56 reversal in the ductus arteriosus with right heart obstructive lesions and should prompt a careful review of the left heart
lesions and flow reversal in the ascending aorta with lesions structures including the mitral valve and arch and may
that impact left ventricular output. prompt a follow-up evaluation to assess in utero growth of
the left heart. Systemic venous anomalies may be found in circulatory patterns. The normal atrial septum in the fetus 4
isolation, but are also often a part of more complex lesions is characterized by the presence of the foramen flap, which
as seen in heterotaxy (Figure 3B). A careful evaluation for opens towards the left atrium and demonstrates low velocity
FEtal Cardiology
situs abnormalities is warranted. flow from right to left with a transient left to right flow in
2. Pulmonary venous anomalies: Include variations in return late diastole.58 The foramen ovale also serves as an obligate
such as total anomalous pulmonary venous connection shunt in the setting of congenital heart defects such as right
(TAPVC) and partial anomalous pulmonary venous and left heart obstructive lesions, transposition of the great
connection (PAPVC) or pulmonary vein atresia. Pulmonary arteries and also total anomalous pulmonary venous return.
venous Doppler show characteristic changes in setting of Prenatal restriction of the foramen ovale has been reported
high left atrial pressures and have been well-characterized in 6 to 22 percent of cases in these settings and is associated
(Figures 15A to D). Obstructed total anomalous pulmonary with poorer outcomes both in fetal and postnatal life.59–61
venous drainage can be a true surgical emergency in the It can be a true emergency in the delivery room in some
delivery room. It is important to identify at least one vein cases and has important implications for delivery planning.
from each lung as entering the left atrium on screening scans The presence of restriction may be indicated by a bulging
to avoid missing diagnosis of total anomalous pulmonary tense appearing foramen with either restricted motion or
venous return. Subtle features suspicious for TAPVR hypermobile motion, straight septum with small opening
include mild right heart enlargement in setting of RV: LV by 2 dimensional imaging, the presence of turbulent flow
disproportion as well as the presence of a vascular structure across it by color Doppler and elevated velocities in excess
in the space between the left atrium and the descending of a 1 m/sec,62–64 (Figure 10). The appearance of the atrial
aorta on four chamber views (Figure 14). Rarely, a cor septum will vary depending on the underlying lesion.
triatriatum may mimic this picture. Pulmonary venous Left heart obstructive lesions are associated with a higher
anomalies are also often seen in the setting of heterotaxy incidence of left atrial hypertension.61,65
and may have a significant impact on outcomes in single Atrial septal defects: The presence of a normal foramen
ventricle physiology. Partial anomalous pulmonary venous ovale in fetal life precludes diagnosis of secundum atrial
return is often missed on prenatal scans unless an effort is septal defects in fetal life. Rarely, the absence of a foramen
made to delineate all four veins in each study. flap and a ‘T’ artifact may clue one to the presence of
3. Atrial and ventricular septal abnormalities: one. Sinus venosus defects are typically high or low in
Prenatal restriction of the foramen ovale: Patency of the proximity to the venous inflow and may be diagnosed in
foramen ovale is critical to the maintenance of normal fetal sagittal images profiling the atrial septum (Figure 9A).
A primum atrial septal defect is readily detected on fetal
echocardiograms and occurs either in isolation or in setting
of a complete endocardial cushion defect (Figure 16). This
is described in greater detail below. Lack of atrial septation
may result in a common atrium and is often associated with
a common atrioventricular valve (CAVV).
Ventricular septal defects: Larger VSD’s may be diagnosed
in fetal life based on a dropout in the ventricular septum in
at least two views. Color flow mapping demonstrating very
low velocity bidirectional flow helps to distinguish from
small dropouts due to poor lateral resolution. Malalignment
and outlet defects may not be seen in the standard four
chamber view unless one images the outlet septum in
relation to the outflows (Figure 13). These defects are
often associated with abnormalities of the outflow tracts.
The lack of septoaortic continuity should prompt a closer
assessment with color. The lack of apical offset of the
tricuspid valve may present a clue to an underlying small
inlet VSD confirmed by color flow imaging. Ventricular
septal defects are very common in postnatal life and though
often seen in isolation, they may also exist as part of an
Figure 14: Total anomalous pulmonary venous return: Four chamber underlying syndrome.
view showing presence of pulmonary vein confluence (arrows) in
the space between the left atrium (LA) and descending aorta (Ao).
Endocardial cushion defects: Complete endocardial
Note: The LA and left ventricle are well-developed in this case. cushion defect includes a primum atrial septal defect with
RA = Right atrium; S = Spine. (Image courtesy: Dr Bettina Cuneo) an inlet ventricular septal defect and a CAVV, however, 57
http://vip.persianss.ir
1
Embryo to thE NEoNatE
Figures 15a to d: Change in pulmonary venous tracing with increasing left atrial pressure in setting of
restriction at the foramen ovale in left heart obstructive lesions: A. Normal pattern with S, D waves and lower
A velocities; B to D. With increasing left atrial pressure there is an increase in ‘A’ reversal and a decrease in
‘D’ velocities till a biphasic pattern with a forward ‘S’ and reversed ‘A’ wave (D)
incomplete forms may be present. This defect is easily as part of a more complex CHD in the setting of heterotaxy.
detected based on the absence of the ‘crux’ in the center The lesion may be balanced or unbalanced or favoring
of the heart in four chamber views. Presence of a CAVV one or the other ventricle with resultant hypoplasia of
results in the two atrioventricular valves being at the one ventricle and associated outflow abnormalities.66,67
same level and lack of apical offset of the tricuspid valve Significant atrio-ventricular valve insufficiency is
58 (Figure 16). Endocardial cushion defects are commonly associated with a higher risk for fetal hydrops and fetal
seen in the setting of aneuploidy especially trisomy 21 and demise especially in the setting of heterotaxy syndromes.
atrialization of the right ventricular inflow and right 4
ventricular hypoplasia. This is a lesion where in fetal
physiology is detrimental and is associated with a high
FEtal Cardiology
incidence of fetal heart failure.74,75 The inability of the right
ventricle to generate enough pressure to open the pulmonary
valve mimics pulmonary atresia (functional pulmonary
atresia). Demonstration of some degree of pulmonary
insufficiency by color flow is often a clue towards some
patency of the pulmonary valve. These neonates may
initially demonstrate a ductal dependent pulmonary blood
flow physiology till a drop in the pulmonary vascular
resistance allows for better ventricular ejection.
5. Pulmonary valve abnormalities: Include pulmonary
stenosis, atresia and absent pulmonary valve syndrome or
dysplastic pulmonary valve. Milder forms of pulmonary
valve stenosis are common in the postnatal period, but are
often missed in midgestation scans. Subtle findings such as
a thickened valve, mildly dilated main pulmonary artery
along with the presence of mild regurgitation of the valve
Figure 16: Balanced complete common endocardial cushion defect: by color Doppler, with or without elevation in Doppler
Note: Lack of ‘X’ at crux. The normal offset of atrioventricular valves
is lost and a common atrioventricular valve is noted separating the
velocities, may indicate the presence of an underlying
ventricular septal defect (arrow) from the primum atrial septal defect abnormality (Figure 6). In utero progression may result in
(dashed arrow). Note: Pulmonary vein draining into the left atrium severe stenosis or rarely atresia.
(arrow head). The ventricles are equal in size. DAo = Descending In pulmonary valve atresia, there is no demonstrable
aorta; LV = Left ventricle; RA = Right atrium; Rt = Right.
flow across the pulmonic valve and there is ductal
dependent pulmonary blood flow, and the ductus arteriosus
demonstrates reversal of flow, i.e. from the aorta to
4. Tricuspid valve abnormalities: Tricuspid valve abnor- the pulmonary artery (Figures 17A and B). The branch
malities may range from subtle minor abnormalities with pulmonary arteries are typically small but confluent in
mild tricuspid insufficiency to significant abnormalities cases with an intact ventricular septum. Branch pulmonary
such as tricuspid valve dysplasia with thickened leaflets, artery abnormalities are in general more likely in the
Ebstein malformation with mild to severe downward setting of pulmonary atresia with a VSD, which falls in
displacement of the septal leaflet with associated stenosis the realm of tetralogy of Fallot and is discussed later.
and regurgitation, tricuspid valve hypoplasia and stenosis Pulmonary atresia with intact septum is associated with
to atresia.68 The tricuspid valve plays an important role in varying degrees of right ventricular and tricuspid valve
fetal circulation given that fetal right ventricle functions hypoplasia ranging from a very small hypoplastic right
against systemic pressures. The normal tricuspid valve ventricle along the lines of a single ventricle, to those
in the fetus is usually fully competent and any trivial where in a tripartite right ventricle is noted and prenatal
insufficiency is usually limited to early systole.69,70 decision making in terms of a two ventricle versus single
Pan-diastolic tricuspid regurgitation is abnormal and ventricle repair becomes challenging.53,54,72,73 Important
suggests either an underlying abnormality or an alteration issues in these cases include the morphology and size of
in right ventricular afterload. Significant right heart lesions the right ventricle as well as tricuspid valve growth. The
are often associated with abnormalities in venous flow range of surgical options are described in chapter 40 in this
patterns suggestive of elevated right atrial pressures and book. Coronary sinusoidal connections can be suggested
are not predictive of outcomes in this setting.71 prenatally by presence of to-fro flow along the surface of
Severe tricuspid valve stenosis or atresia is often seen the heart and presence of a dilated proximal coronary.
in the setting of a single left ventricle. As in cases of Rarely, a dysplastic pulmonary valve may be noted with
pulmonary stenosis, even cases that appear not quite severe a combination of severe stenosis and insufficiency. In these
in early second trimester, may progress in severity with lack cases there is right ventricular enlargement. As with other
of right ventricular growth and resultant single ventricular volume loading conditions there is a risk for hydrops and
physiology in late gestation and serial evaluation during fetal loss in these cases.
pregnancy is necessary.54,72,73 6. Mitral valve abnormalities: Isolated mitral valve abnor-
Ebstein malformation of the tricuspid valve involves malities are unusual and are usually seen in the setting of
varying degrees of apical displacement of the valve and associated abnormalities of the left ventricle and aortic 59
resultant enlargement of the right atrium secondary to valve. The combination of a dysplastic mitral valve with
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b
Figures 17a and b: Double outlet right ventricle with severe pulmonary stenosis: A. Origin of both great vessels from the right ventricle (RV).
A small pulmonary artery (PA) is noted crossing anterior to the aorta (Ao); B. Sagittal images show a small curlicue ductus arteriosus (DA) with
reversed flow feeding small confluent branch pulmonary arteries (PA). LV = Left ventricle, S = Spine
associated stenosis and severe regurgitation presenting These findings may be subtle in the early second trimester
with severe left ventricular and left atrial dilatation and scan and may be missed, especially on screening studies.
ineffective left ventricular ejection is usually associated More severe stenosis may be associated with altered flow
with poor outcomes.76,77 This lesion is characterized by a patterns across the distal arch with retrograde filling being
high risk for prenatal restriction at the level of the foramen noted in the transverse arch with or without associated arch
ovale given elevated left atrial pressures; associated right hypoplasia (Figure 10B).
heart failure due to impairment of right ventricular filling The combination of a hypoplastic left ventricle with
in the setting of a dilated hypocontractile left ventricle varying degrees of aortic valve stenosis/atresia and
(Figure 10). There is a high risk for hydrops in these cases. mitral valve stenosis/atresia with aortic arch hypoplasia
In utero intervention in terms of balloon dilatation of the constitutes hypoplastic left heart syndrome. However,
foramen ovale has been attempted in some cases. It is often many different combination of lesions may share the
difficult to distinguish this from severe aortic stenosis with physiology and surgical options. For example, a dysplastic
secondary mitral valve insufficiency. The aortic valve mitral valve may preclude a two ventricle repair even
though small will often show low velocity laminar forward though the left ventricle and aortic valve may be deemed
flow in these cases. In many situations associated with adequate.66,77–79 Significant aortic stenosis and variations
mild left ventricular hypoplasia, the mitral valve lesion is of hypoplastic left syndrome result in a ductal dependent
often the limiting factor for a two ventricle repair. A cleft systemic circulation (Figure 10B).
in the mitral valve may be seen in setting of an endocardial 8. Conotruncal lesions: Common lesions include tetralogy of
cushion defect and is best seen in the sagittal images of the Fallot, truncus arteriosus, transposition of the great vessels
left ventricle with the mitral valve ‘en-face’. and double outlet right ventricle amongst others. All of
7. Aortic valve disorders: Include stenosis, atresia and these lesions share defects in septation of the conotruncus
associated left ventricular abnormalities. The left ventricle or formation of the aorticopulmonary septum and are often
may be dilated or hypoplastic or may show evolution from associated with a malalignment type VSD (except simple
one to the other in later gestation. Isolated mild aortic D-transposition of great vessels). Interrupted aortic arch
valve stenosis in the setting of an otherwise normal left with a VSD falls in the same category, but is discussed
ventricle may be difficult to diagnose in fetal life. Clues with arch anomalies given that a VSD is not universally
include subtle dilation of ascending aorta, thickened aortic present. Associated chromosomal abnormalities, including
valve leaflets on 2D imaging and aliasing of color flow 22q11 deletions and aneuploidy, have been reported in
across the valve and elevated flow velocities across the 17 to 26 percent of cases and may affect counseling and
60 valve by Doppler or subtle right ventricular enlargement. outcomes.3,80–82 The outflow tract, 3 VV and tracheal
4
FEtal Cardiology
a b
Figures 18a and b: A. Truncus arteriosus. A single outflow or truncus (Ao) is noted that gives rise to the branch pulmonary artery (arrow) and
head and neck vessel (**); B. Three vessel view in a fetus with pulmonary atresia and bilateral superior vena cava (SVC). Confluent small branch
pulmonary arteries (arrows) noted in close proximity to the large aorta (Ao). Closer assessment reveals a small hypoplastic main pulmonary
artery segment wrapping around (arrow head) to the left of the aorta. S = Spine
views are important in the evaluation of the conotruncus lack of crossing of the aorta and pulmonary artery in the
and great vessels with supplemental information from the outflow views, along with a posteriorly placed pulmonary
sagittal and transverse scans.83–85 vessel that shows lateral branching (Figure 12).
Tetralogy of Fallot: It is associated with anterior D-transposition of the great vessels is characterized
deviation of the conal septum with resultant aortic override, by atrioventricular concordance and ventriculoarterial
malalignment VSD and varying degrees of sub- and valvar discordance. Four chamber views are normal however,
pulmonary stenosis. The right ventricular hypertrophy outflow tract views reveal parallel great vessels. The 3
is a normal feature in fetal life. This lesion is associated VV/tracheal views are abnormal as the ductal and aortic
with varying degree of hypoplasia of the pulmonary arch will superimpose and result in lack of the normal ‘V’
arteries (Figure 6C). With severe outflow tract obstruction seen in the tracheal view. Though well-tolerated in fetal
and with pulmonary atresia the pulmonary blood flow is life this results in significant desaturation after birth and
ductal dependent and there is reversed flow noted in the significant hypoxemia can result especially in the setting
ductus arteriosus.86 Rarely, in the setting of pulmonary of poor mixing at the atrial and ductal level. In about 13
atresia, the lesion may be mistaken for a truncus arteriosus percent of cases there can be in utero restriction at the level
(Figures 18A and B). Color flow evaluation of the arch in of the foramen ovale with resultant failure to resuscitate in
sagittal views may reveal the presence of aortopulmonary the delivery room or early neonatal death in unrecognized
collaterals. A variant of this defect is tetralogy of Fallot cases. A hypermobile foramen, restrictive foramen
with absent pulmonary valve syndrome. This lesion, flow and diastolic reversed flow in the ductus arteriosus
characterized by aneurysmal dilated branch pulmonary have been suggested as predictors for an urgent balloon
arteries and a dilated right ventricle in the setting of severe septostomy.64,88
pulmonary insufficiency, has poorer fetal and postnatal L-loop transposition of the great vessels is character-
outcomes.87 Severe air trapping may be seen in postnatal ized by the presence of atrioventricular and ventriculoarte-
period, in the setting of tracheobronchial compression rial discordance, which results in physiologically corrected
from the dilated pulmonary vessels and hence these fetuses flows. The clinical picture is dictated by the associated
are best delivered at a tertiary care center. lesions, which are reported in upto 85 percent of cases and
Transposition of the great vessels: These include D-loop include VSDs, left atrioventricular (tricuspid valve) ab-
transposition and L-loop transposition of the great vessels. normalities, pulmonary and subpulmonary stenosis, heart
From the standpoint of fetal echocardiogram both these block and arch abnormalities.89,90 There is an incremental
defects show a parallel orientation of the great vessels, with risk for complete heart block in this setting and this may 61
http://vip.persianss.ir
1 often be the presenting feature in fetal life. Echocardiogra- enlargement in the second trimester was associated with
phy reveals an abnormal four chamber view with the right arch abnormalities in 60 percent of fetuses in one series.93
ventricle being posterior and parallel outflows, with the Markers including the presence of isthmic hypoplasia or
Embryo to thE NEoNatE
aorta being situated anterior and to the left of the pulmo- a Z score of less than -2, presence of a posterior shelf and
nary artery. an isthmus to ductus diameter ratio less than 0.74.56,94
Double outlet right ventricle: In this defect both great Fetal diagnosis of a coarctation remains very challenging,
arteries arise from the right ventricle (Figure 17). The especially in the third trimester due to the normal presence
clinical picture is dictated by the variable relation of the of right ventricular prominence and tortuosity of the
great vessels to each other, the relationship of the VSD to ductus arteriosus in late gestation and variable postnatal
the great arteries and presence or absence of stenosis of presentation.95
one of the semilunar valves. Relative hypoplasia of one of The ductus arteriosus has a major role in fetal circulation
the ventricle may be seen. A systematic approach to outline acting as a conduit of most of the fetal systemic blood flow
the connections and alignment of the different cardiac to the lower body with aortic isthmus only seeing about 7
segments is needed to elucidate the physiologic effect of to 10 percent of the combined cardiac output. Inadequate
the lesion. It is particularly important on prenatal scans forward flow from the right heart results in flow reversal in
to identify the fetus at risk for ductal dependent systemic the ductus arteriosus from the aorta to the pulmonary artery
circulation as in the setting of aortic stenosis and arch and serves as a marker for ductal dependent pulmonary
hypoplasia or as is more commonly seen, ductal dependent blood flow in postnatal period (Figure 17B). Similarly, in
pulmonary circulation in the setting of severe pulmonary cases of inadequate left ventricular cardiac output there is
stenosis or atresia. Outcomes depend on the subtype and retrograde filling of aortic arch from the ductus arteriosus
association of chromosomal abnormalities.91 and hence a marker for ductal dependent systemic blood
Truncus arteriosus: It results from failure of aortico- flow (Figure 10B). Prenatal restriction of the ductus has
pulmonary septum to form completely. This is characterized been reported in the setting of both a normal heart as well
by the presence of a single large vessel that overrides the as setting of CHD.63 It may result from maternal exposure
ventricular septum and gives rise to both the aorta and to medications such as indomethacin and its analogues
the branch pulmonary arteries (Figure 18A). Important and has been reported with high dietary polyphenol
differential includes tetralogy of Fallot with pulmonary exposure.96–98 Narrowing may be noted on 2D imaging
atresia and aortic atresia with a VSD. 22q11 deletion along with turbulent color flow and elevated diastolic flow
may be found in 30 to 40 percent cases.92 Associated velocities across the ductus and results in right ventricular
abnormalities include a right aortic arch, interruption of hypertrophy, enlargement and progressive tricuspid
the arch, truncal valve stenosis and regurgitation. Inability regurgitation. If no correctable cause is noted then early
to document head and neck vessels from the only arch and delivery may be indicated with resultant improvement
the presence of a larger than normal first head and neck in right ventricular function. Elevated ductal flow may
vessel that is directed straight up should raise suspicion of be seen in high output states.99 Ductal constriction is
ductal continuation of the aorta. A dysplastic truncal valve associated with a decrease in pulsatility index (PI) of less
with severe stenosis or insufficiency may adversely affect 1.9, where as high output states result in as elevated PI. In
prognosis. utero ductal restriction in the setting of underlying CHD
9. Aortic arch and ductal abnormalities: The addition such as transposition of the great arteries is associated with
of the three vessel and tracheal views have significantly a poorer outcome and serial evaluation through pregnancy
added to the assessment of the variations in ductal and is recommended to adjust delivery management.
aortic arch anatomy including lesions such as interruption The ductus arteriosus is often smaller and curlicue in
of the aortic arch, aortic arch hypoplasia, variations in the setting of conotruncal lesions associated with severe
arch sidedness, variations in ductal morphology including right ventricular outflow tract obstruction (Figure 17B).
ductal aneurysm, and vascular rings (Figure 7). Diastolic flow reversal in the ductus arteriosus in setting
Type B interruption demonstrates ductal continuation of transposition of the great arteries may be a marker
of the descending aorta and a straight appearance to the for prenatal restriction of the atrial septum and has been
ascending aorta. There is a high association with a mal- associated with persistence of pulmonary hypertension in
alignment VSD, various degrees of subaortic obstruction the newborn.63,64
and 22q11 deletion. 10. Complex CHD: A segmental approach is critical to
Isolated coarctation of the aorta is difficult to reliably the diagnosis of complex CHD, with a view towards
diagnose in fetal life in the absence of arch hypoplasia. establishing the anatomic diagnosis along with the
The redistribution of flow results in relative prominence functional consequence. Heterotaxy syndromes are often
of the right ventricle. Though there are other causes for associated with significant cardiac defects that include
62 right ventricular prominence, presence of right heart variations in systemic and pulmonary venous return,
cardiac looping and outflow abnormities. In these cases, limitations of Fetal echocardiograms 4
the risk for associated rhythm abnormalities, malrotation
of the intestines and abnormal splenic function may Though a high degree of diagnostic accuracy has been
FEtal Cardiology
impact postnatal management and should be addressed at achieved with a comprehensive fetal echocardiogram,
the time of counseling. several lesions may be difficult to diagnose or missed in the
11. Miscellaneous heart defects: Intracardiac masses—A prenatal period given inherent limitations of fetal physiology
range of cardiac tumors may present in fetal life. and resolution by ultrasound. These include small VSDs,
Rhabdomyomas are the most common followed by isolated minor valvular lesions, secundum or sinus venosus
teratomas, fibromas and hemangiomas amongst others.100,101 atrial septal defects, partial anomalous pulmonary venous
Cardiac consequences may occur due to effects of the tumors return, isolated coarctation of the aorta and importantly late
on blood flow across the valves resulting in obstruction to gestational changes in form or function.
blood flow or regurgitation of the valve; local impact on
the myocardium resulting in poor contractility or irritability In utero Course and ImPlICatIons For
and cardiac arrhythmias; local effects such as development delIVery PlannIng
of pericardial effusions and tamponade. Serial monitoring
of cardiac function, tumor size and its hemodynamic impact The main goal of prenatal diagnosis is to afford adequate
is needed during pregnancy. Rhabdomyomas may regress counseling to families with regards to implications of the
after birth, but are associated with tuberous sclerosis in up cardiac lesion and to plan follow-up, delivery and neonatal
to 80 percent of cases and the postnatal course is dominated care. A positive impact on survival has been shown only in
by the neurologic consequences of the same.102 If identified certain lesions, however, several studies have shown an
prenatally, formal genetic counseling and evaluation for improvement in preoperative variables.106–109 Data suggests
tuberous sclerosis is indicated. that one in three infants with a potentially life-threatening
Echogenic foci appear as discrete ‘echo-bright’ or echogenic lesion leave the hospital undetected.110,111 Fetal diagnosis of
spots in the submitral or subtricuspid valvular apparatus and CHD in general, tends to be on the severe end of the spectrum
move with the cardiac valves, are often noted on routine scans. given that most are picked up on screening studies. There is in
They are thought to represent areas of ectopic calcification or general a higher risk for fetal loss in the setting of chromosomal
fibrosis. It is important not to mistake them for cardiac tumors. abnormalities especially with Turner’s syndrome.
These do not affect cardiac function. In general, fetal CHD is well-tolerated in fetal life given the
presence of shunts at the level of the foramen ovale and the
Cardiac diverticulum and aneurysms are rare lesions ductus arteriosus. Obstructive lesions involving one ventricle
affecting the ventricles or atria that may be noted on fetal are compensated by redirection of flow across the foramen
echocardiograms. Aneurysm are thin walled, lack myocardium, ovale to the other ventricle. As long as the combined cardiac
have a wide attachment to the ventricle and tend to fill with output is relatively maintained by the other ventricle the fetus
ventricular systole, while a diverticulum has a narrow neck, has does well. Congenital heart defects that are poorly tolerated in
myocardium and contracts in synchrony with the ventricle.103,104 fetal life include those associated with:
A ventricular diverticulum may be idiopathic or seen in the • Prenatal restriction at the foramen ovale with or without
setting of herniation of a part of the ventricle through an anterior associated CHD
chest wall defect as with pentalogy of Cantrell. It may be difficult • Prenatal restriction at the level of the ductus arteriosus with
to prenatally distinguish between the two. They may present in or without associated CHD
association with pericardial effusion, needing pericardiocentesis • Significant valvular insufficiency (e.g. Ebstein malforma-
in setting of cardiac dysfunction or if progressive, to prevent tion, absent pulmonary valve syndrome)
lung hypoplasia; cardiac arrhythmias or rupture with fetal death. • Poor myocardial function (e.g. myocarditis, myocardial
In utero as well as postnatal resolution has been described.105 non-compaction, heart failure)
• Arrhythmias: both tachy- and bradyarrhythmia, especially
Cardiomyopathy: Fetal cardiomyopathy may have a diverse in the setting of associated CHD
presentation and may result from many different causes • Associated placental insufficiency and intrauterine growth
as in postnatal life. Fetal anemia and myocarditis may retardation.
mimic dilated cardiomyopathy. A picture of hypertrophic
cardiomyopathy may be idiopathic or seen in the setting of Progression of lesions
Noonan syndrome in the fetus, severe uncontrolled diabetes
mellitus in mother, right ventricular hypertrophy in the The potential for progression of fetal heart disease has an
recipient twin in TTTS. Non-compaction cardiomyopathy important bearing on prenatal counseling with regards to
may coexist with arrhythmias and complex CHD in prognosis and planning of prenatal and neonatal management.
heterotaxy syndromes. This progression may happen at many levels such as: 63
http://vip.persianss.ir
1 • Progressive increase in degree of stenosis or resultant foramen ovale.55,79,113,115 There appears to be an improvement
atresia of valves in hemodynamics with growth of the inflow and outflow,
• Lack of growth of a chamber or vessel with resultant ductal but growth of the left ventricle itself is not as robust. Fetal
Embryo to thE NEoNatE
dependent systemic or pulmonary blood flow. This may mortality is about 10 percent. A threshold scoring system
ultimately change surgical options with potential need for for prediction of a biventricle outcome has been developed
a univentricular repair rather than biventricular repair. by the Boston group in an effort to predict a two ventricle
• Progressive regurgitation of a valve with risk for fetal outcome.55,116
hydrops and implications for delivery
• Development of significant restriction at the level of the Creation or Enlargement of Inter-atrial Communication
foramen ovale and/or ductus arteriosus with implications
for timing, type and place of delivery; given potential need In utero restriction of the foramen ovale is associated with
for urgent intervention and high risk for fetal and early poor postnatal outcomes secondary to poor oxygenation and
neonatal demise chronic left atrial hypertension with resultant pulmonary
• Myocardial dysfunction may develop with resultant fetal venous hypertension. Technically, this is more challenging
heart failure given the small atria. Though successful in utero stenting of the
• Development of fetal arrhythmias needing medical mana- atrial septum has been reported, however an improvement in
gement or impacting timing of delivery outcomes has not been clear, given the small numbers. Timing
• Progression or regression of a cardiac tumor. of intervention, size of defect created and relief of associated
significant aortic stenosis may all have an impact.114,116,117
Fetal Cardiac Interventions
Pulmonary Valvuloplasty
As our understanding of the in utero progression of certain
lesions evolve, there has been an attempt to alter or limit the Pulmonary atresia with intact septum or highly restrictive
progressive changes by in utero intervention. On a broader VSD is associated with varying degrees of right ventricular
slate, prenatal interventions include the use of transplacental hypoplasia and tricuspid valve involvement, which is often
antiarrhythmic medications in fetal arrhythmias or use of the limiting factor to a two ventricle repair. In utero dilatation
Digoxin for inotropy. However, in terms of progressive structural of the pulmonary valve has been successfully performed and
lesions most of the recent advances have been in the setting improvement in right ventricular growth demonstrated on
of percutaneous fetal cardiac interventional procedures. Fetal follow up.114,118,119 The procedure is technically challenging
‘open’ cardiac surgery has been limited by the high incidence and case selection and technological advances is a subject of
of preterm labor in these cases.112 With closed interventional current investigation.
approach, a high degree of technical success has been achieved
especially in left heart lesion. The success in prevention of a delivery Planning
single ventricle physiology is dependent on case selection,
timing of intervention and the underlying diagnosis and these In general, delivery is best done as close to term as possible
are evolving. Methodological advances are being made. A in the setting of complex congenital heart defect to avoid
handful of centers across the world are involved in a systematic complications of associated lung disease of prematurity.
approach to these lesions given ethical considerations. Several However, these decisions have to be made on a case by
recent publications have addressed the technical aspects, case case basis, weighing the risk benefit ratio of continuing the
selection as well as world-wide results.113–116 pregnancy to those of prematurity.
Interventional approach has been applied to primarily three Type of delivery is usually dictated by obstetric needs
subsets: except in certain situations such as:
• Concerns for poor myocardial reserve in the fetus in setting
Balloon Valvuloplasty of the Aortic Valve of heart failure or hydrops where in the stress of a vaginal
delivery may not be well-tolerated.
For aortic stenosis with a normal or large left ventricle and • Fetal arrhythmias such as complete heart block or tachy-
poor function, with a view towards promoting growth of arrhythmias where in monitoring of fetal well-being in
the left ventricle and thus prevent the need for a single labor may be difficult
ventricle repair. Inclusion criteria which reflect predictors for • Presence of anterior abdominal or chest wall defects.
development of HLHS includes: critical aortic stenosis as the • Significant prenatal restriction at ductal or atrial level
dominant lesion, presence of retrograde flow across the arch, where in immediate postnatal intervention is contemplated.
monophasic mitral inflow pattern, normal sized or dilated left An early delivery may be considered in some cases in
ventricle with diminished function, right to left flow at the the setting of progressive hydrops, especially in the setting
64
of right heart failure where in the fetal physiology is more combined cardiac output after midgestation; estimated to 4
detrimental to cardiac function as in Ebstein malformation be about 60 percent at about 38 weeks.120,121 The combined
or severe prenatal ductal constriction, intractable arrhythmias cardiac output in the human fetus is estimated to be about 425
FEtal Cardiology
not responsive to medical management, progressive placental to 550 mL/kg/min.122 Heart failure in the fetus manifests as
dysfunction and markers for poor fetal well-being or for features of increased central venous pressures characterized
maternal causes. by fluid accumulation and diminished cardiac output with
Factors predictive of the need for neonatal intervention and associated decentralization of flow. Hydrops fetalis is defined
planned delivery include: as the presence of two or more of the following: pleural or
• Prenatal restriction at the level of foramen ovale or ductus pericardial effusion, ascites or skin edema.
arteriosus
• Obstructed pulmonary venous return etiology of heart Failure
• Ductal dependent systemic or pulmonary circulation or
potential for the same Heart failure in a fetus may result from one or a combination
• Poor myocardial function and heart failure of physiologic factors in a variety of clinical settings both
• Presence of fetal hydrops cardiac and non-cardiac as outlined in Box 1.
• Uncontrolled arrhythmias: Tachyarrhythmia or bradyarr- Secondary cardiac dysfunction has now been recognized in
hythmia. a variety of extracardiac conditions. Volume overload occurs in
Most congenital heart defects are well-tolerated in the the setting of fetal anemia, arteriovenous malformations as in
delivery room and the stabilization of ductal dependent vein of Galen malformation, vascular tumors as in hemangiomas
lesions can be achieved with the use of prostaglandin E1 and sacrococcygeal teratomas, congenital absence of the
(PGE1) infusion. However, the presence of restrictive fetal ductus venosus when associated with an extrahepatic vascular
pathways, obstructed pulmonary venous return, airway shunt. Studies have shown that a combined cardiac output of
obstruction or severe myocardial dysfunction may present as greater than or equal to twice the normal indexed combined
true emergencies in the delivery room and arrangement for cardiac output result in the evolution of hydrops and this may
delivery at a tertiary care center with availability of immediate
interventional, surgical or ECMO support, depending on the
underlying issues is critical. box 1: Causes of fetal congestive heart failure
Other lesions that are not ductal dependent such as
a complete common atrioventricular canal that is well- 1. C
ongenital heart disease associated with valvular
balanced, VSDs or conotruncal lesions that are not clearly insufficiency:
ductal dependent are managed differently in different settings, • Ebstein malformation and tricuspid valvular dysplasia
depending on the standard of care available locally. The • Mitral valve dysplasia
• Absent pulmonary valve syndrome and severe pulmonary
availability of teleconferencing and the ability to read studies
stenosis
remotely and availability of PGE1 has made it easy to stabilize • Dysplastic common atrioventricular valve
neonates locally and allow for transport in a timely fashion if • In utero constriction of ductus arteriosus or foramen ovale
needed. • Dysplastic truncal valve
2. Fetal arrhythmias:
• Sustained tachyarrhythmia with HR > 220/min
• Sustained bradyarrhythmia with FHR < 55/min
FunCtIonal assessment oF Fetal CardIaC 3. High output states:
FunCtIon and Fetal heart FaIlure • Fetal anemia: Maternal parvovirus infection, immune medi-
ated
The systematic application of ultrasound and Doppler to • Vascular tumors: Sacrococcygeal teratomas, placental
the evaluation of the fetal circulatory state has provided us chorioangioma
• Arteriovenous malformation: Vein of Galen
with a unique insight into fetal circulatory system and its
• Agenesis of ductus venosus
compensatory mechanisms to conditions associated with 4. Extrinsic cardiac compression:
cardiovascular stress. Clinical features suggestive of congestive • Diaphragmatic hernia
heart failure after birth can be elucidated based on changes in • Congenital cystic adenomatoid malformation
cardiac function and Doppler parameters in the fetus. 5. Primary myocardial dysfunction:
The fetal circulation is a parallel circulation characterized • Fetal cardiomyopathy
• Fetal myocarditis
by the presence of shunts across the foramen ovale, ductus
• Intracardiac tumors (also cause valvular dysfunction)
arteriosus and the ductus venosus. Though early in gestation, 6. Recipient in twin-to-twin transfusion syndrome
the relative outputs of the two ventricles are similar, the 7. Severe uteroplacental insufficiency (IUGR)
right ventricle contributes to an increasing proportion of the
65
http://vip.persianss.ir
1
Embryo to thE NEoNatE
Figure 19: Pathophysiology and cardiovascular manifestations in twin-twin transfusion syndrome. The recipient twin is subject
to a mixed physiology secondary to volume overload as well as pressure overload secondary to transmitted vasoactive
mediators from the donor twin with resultant right ventricular cardiomyopathy and associated left ventricular dysfunction.
LV = Left ventricle; MR = Mitral regurgitation; RV = Right ventricle; RVOTO = Right ventricular outflow tract obstruction;
TR = Tricuspid regurgitation.
influence decision to intervene.123–125 Cardiovascular findings evaluation of Fetal Cardiac Function and
include cardiomegaly, atrioventricular valve regurgitation and Changes in Fetal heart Failure
abnormal Doppler. Extrinsic compression on the heart may Evaluation of fetal heart function involves a comprehensive
impede venous return and affect myocardial contractility and systematic assessment of the fetal cardiovascular system
and result in heart failure as in diaphragmatic hernia and including the following:
CCAM.126 • Cardiac function
Conditions associated with a high afterload such as • Assessment of hemodynamic consequences:
placental dysfunction and the recipient twin in TTTS can result – Venous Doppler
in cardiac failure. In the fetal circulation, the right ventricle is – Arterial Doppler
particularly susceptible to the effects of high afterload imposed • Signs of congestive heart failure: Evaluation for hydrops
by placental insufficiency and this may result in ventricular Assessment of fetal cardiac function and myocardial
hypertrophy, altered diastolic function and systolic dysfunction. performance: Several parameters help in the assessment
TTTS complicates about 10 to 15 percent of all monoamniotic- of cardiac function (Figures 20A to E). Cardiac outputs
dichorionic (MoDi) pregnancies. It is characterized by a mixed can be calculated using Doppler data (Figures 21A and B).
picture of volume overload in the setting of a high afterload Atrioventricular valve inflow patterns in the fetus typically
in the recipient fetus (Figure 19). The presence of placental show ‘A’ wave dominance with an E/A ratio of less than 1.
vascular communications allows for the transmission of Increasing stiffness of the ventricle is reflected in the presence
vasoactive mediators secreted by the donor fetus in response of a ‘monophasic’ inflow pattern characterized by ‘A’ wave
to hypovolemia. Progressive right ventricular dysfunction alone. Elevated filling pressures result in increasing atrial flow
results, with associated left ventricular dysfunction, tricuspid reversal in venous Doppler. Vector velocity mapping has been
insufficiency with progression to hydrops consistent with an applied for assessment of fetal myocardial properties recently
acquired cardiomyopathy.123 In utero therapy with laser ablation and has the advantage of being angle independent though it is
of placental vascular connections can lead to stabilization and affected by frame rates.129 Myocardial performance index has
improvement in cardiac status and outcomes. Acquired sub- been used as a measure of global function and can be altered
pulmonary stenosis and evolution to pulmonary atresia has with systolic or diastolic dysfunction.130,131 Alterations in
been reported. Findings of right ventricular cardiomyopathy myocardial performance index (MPI) have been reported
are absent in stage 1 and 11 of the Cincinnati modification of in the setting of CHD, altered afterload as in diabetic
66 the Quintero classification and allows for a trial of expectant pregnancies and TTTS. Progressive ventricular dilatation
management with or without amnioreduction.22,127,128 and hypertrophy in the setting of elevated afterload, results
4
FEtal Cardiology
a
b C
E
Figures 20a to E: Methods used in assessment of cardiac performance: A. Systolic function can be estimated qualitatively by assessment
of wall motion by 2D and can be quantified by calculating fractional shortening (FS) based on M-mode recordings; B. Presence of valvular
insufficiency with a normal valve suggests diastolic dysfunction and can help assess ventricular pressures; C. Increasing ventricular stiffness and
elevated filling pressures results in loss of passive filling and augmented atrial filling with a resultant monophasic inflow pattern; D. Method for
calculating myocardial performance index (MPI) by inflow outflow Doppler. ICT = Isovolumic contraction time; IRT = Isovolumic relaxation time;
SEP = Systolic ejection period; E. Tissue Doppler assessment for assessing diastolic properties. Supplementary information on fetal heart rate
and rhythm is obtained by M-mode as well as Doppler evaluation
Venous dopplers
in atrioventricular valve insufficiency. The presence of holo-
systolic tricuspid insufficiency is abnormal and merits close Studies in both animals and human fetuses have shown that
follow-up. Normalization of afterload as seen with reversal alterations in central venous blood flow patterns accurately
of ductal constriction with cessation of indomethacin therapy reflect changes in hemodynamics. Normal venous flow
or s/p laser ablation in setting of TTTS results in a prompt patterns in the systemic veins show biphasic forward flow; 67
improvement in degree of tricuspid regurgitation and can be corresponding to the ‘S’ wave with ventricular systole and ‘D’
used as a marker for improving hemodynamics. wave during early diastole followed by a transient negative or
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b
Figures 21a and b: Measurement of right ventricular cardiac output (RVCO): A. Short axis image demonstrating the right ventricular outflow
tract, measurement of pulmonary annulus diameter (D) and placement of Doppler sample; B. Pulmonary artery Doppler signal is used to
measure velocity time integral (VTI) and heart rate (HR). Formula for calculation of cardiac output using above parameters. Left ventricular
cardiac output (LVCO) can be calculated from measurement of aortic annulus and Doppler flow velocity across the left ventricular outflow tract.
Combined cardiac output equals LVCO + RVCO
‘A’ reversal in association with atrial contraction. In the ductus box 2: doppler indices
venosus, atrial contraction results in decreased flow velocity
but maintains forward flow. Normal umbilical vein shows Commonly used venous doppler indices:
non-pulsatile flow. Increasing central venous pressure leads 1. Preload index (IVC): Peak A velocity/peak S velocity
2. Pulsatility index for veins (DV): Systolic-diastolic (a) velocity/
to progressive increase in ‘a’ wave reversal starting from the
time averaged maximal velocity
hepatic veins and IVC through the ductus venosus and hence 3. Percentage reverse flow: Time velocity integral (S+D)/time
to the umbilical veins with increasing severity.132,133 Early velocity integral A reversal
venous Doppler changes indicative of high filling pressures
Commonly used arterial doppler indices:
may be seen normally in the setting of CHD associated 1. SD ratio: Systolic/diastolic ratio
with right heart obstructive disease, but should be non- 2. Pulsatility index (PI): Systolic velocity–diastolic velocity/
progressive in these states.134–136 Similarly, tachyarrhythmias mean velocity
result in abnormal venous Doppler tracing but should show 3. Resistive index (RI): Systolic velocity–diastolic velocity/
normalization during sinus rhythm. Persistence of abnormal systolic velocity
4. Cerebroplacental ratio: Middle cerebral artery PI/umbilical
venous Doppler tracings in sinus rhythm is thought to be
artery PI
indicative of underlying myocardial dysfunction. Doppler
D = Diastolic; DV = Ductus venosus; IVC = Inferior vena cava; S = Systolic.
indices used are noted in Box 2.
Similar changes may be seen in the pulmonary veins in
the setting of elevated left atrial pressures. Normal pulmonary including the middle cerebral artery (MCA) and the umbilical
venous flow shows low velocity forward flow with a ‘S’ and cord. Evaluation of the arterial Doppler patterns enables
‘D’ peak and cessation of flow in atrial systole. Increasing left the assessment of features of decentralization of flow and
atrial pressure results in flow reversal in the pulmonary veins assessment of the fetoplacental unit. Fetal hypoxia results in
with atrial contraction and a decrease in diastolic forward cerebral vasodilatation as a ‘brain sparing’ response, which
flow, ultimately resulting in a biphasic to-and-fro pattern results in a decrease in MCA PI due to increase in diastolic
with absent ‘D’ velocities.65,137,138 Left atrial hypertension flow velocity, in the setting of increased PI in the umbilical
and restriction at the level of the foramen ovale has been artery.139 This results in an increase in cerebroplacental index
associated with poor outcomes.59 (Box 2). Fetal anemia results in an increase in MCA peak
velocity. The healthy placenta is a low resistance circuit and the
arterial doppler umbilical artery shows a systolic peak with continued forward
68 flow in diastole. With progressive placental dysfunction, there
Arterial Doppler can be obtained at several sites including is initially a decrease in diastolic flow velocity followed by
the semilunar valves, great arteries and their branches cessation and then reversed flow in diastole implying a high
table 4 4
Cardiovascular profile score.
Cardiovascular profile score (10 points = normal)
FEtal Cardiology
Feature Normal –1 point –2 points
Hydrops None (2 points) Ascites or pleural effusion or Skin edema
pericardial effusion
Venous Doppler
(Umbilical vein)
(Ductus venosus) UV UV UV pulsations
DV (2 points)
DV
Heart size (Heart area/chest ≤ 0.35 (2 points) 0.35 - 0.50 > 0.50
area) < 0.20
placental resistance.140 Finally, underlying CHD may impact assessment of Fetal rhythm
arterial flow patterns especially in left heart obstructive lesions
and should be taken into account.141–143 Ultrasound is the mainstay in the clinical evaluation and man-
A fetal cardiovascular profile score has been proposed agement of rhythm disorders in the fetus. Fetal echocardio-
by Huhta and colleagues as outlined in Table 4.144 A normal graphy allows for a comprehensive assessment of the fetus
score would be 10 with a decrease in the score with each including:
additional abnormality. A decreasing score has been shown • Assessment of underlying rhythm and elucidation of
to be predictive of poor outcome in the setting of placental mechanism of arrhythmia
insufficiency and primary heart defects.145,146 • Evaluation for associated cardiac malformations
• Serial evaluation/assessment for evidence of heart failure
Fetal arrhythmIas and tolerance of arrhythmia
• Response to therapeutic intervention.
Fetal rhythm disturbances account for about 10 to 20 percent of The assessment of underlying rhythm by ultrasound
referrals to fetal cardiologists.147,148 Most of these are benign and depends on the extrapolation of electrical events based on its
consist of transient irregularity in rhythm and are well-tolerated. mechanical consequence in terms of myocardial contraction
However, persistent tachycardia and bradycardia may result (M-mode, tissue Doppler), its physiologic correlate by
in fetal heart failure and in utero demise. Transplacental drug assessing Doppler flow patterns or a combination of the
therapy has been used effectively, especially in the management two (color M-mode) (Figure 22). The goal is to establish
of fetal tachycardia, providing an impetus for comprehensive the chronologic relationship between atrial and ventricular
assessment of the fetal rhythm in an effort to improve outcomes contraction and their rates, thus inferring the underlying
in these fetuses. Normal fetal heart varies with gestational age, rhythm. Mechanical PR interval can be measured using
but in general ranges from 120 to 160 BPM. Normograms have Doppler techniques and helps to assess A-V conduction times. 69
been published and are available for reference.149,150 (Figures 22 A and B).
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b
C d
Figures 22a to d: Common modalities used in arrhythmia assessment: A. Simultaneous inflow and outflow Doppler obtained with Doppler gate
positioned in the left ventricular outflow tract. Each atrial contraction results in A wave in mitral inflow and ventricular ejection results in flow
into the aorta (V). Mechanical PR interval is measured from beginning of mitral valve ‘A’ to the beginning of ventricular ejection (parallel lines);
B. Superior vena cava (SVC): Aorta or SVC and aortic flow signal. Atrial contraction results in ‘A’ reversal in the SVC tracing and ventricular
ejection in flow in the aorta ‘V’. Lines denote measurement of mechanical PR interval or A-V conduction time; C. Anatomic M-mode showing atrial
contractions (A) followed by ventricular contractions (V); D. Color encoded M-mode showing atrial contractions on M-mode (A) followed by flow
in the aorta documented by color Doppler (E). This allows for optimization of M-mode to record the low amplitude atrial contraction
m-mode which result in fusion of E and A waves and also when atrial
contraction occurs simultaneous with ventricular contraction
Alignment of the M-mode along the atrium and ventricle allows or against a closed atrioventricular valve.
for simultaneous recording of the atrial and ventricular wall Simultaneous sampling of the ascending aorta and the SVC
motion. The quality of the tracings is significantly affected by as it enters the right atrium, demonstrates the relationship
maternal insonation characteristics, fetal position and motion, of the atrial contraction (A reversal in SVC) to ventricular
which may limit the ability to achieve proper alignment. It contraction (forward flow in aorta) (Figure 22B). Using
is often difficult to obtain good quality tracings of one or the this technique one can assess chronological relationships to
other chamber and atrial signals may be of low amplitude in ascertain the rhythm and measure ventriculoatrial (VA) and
setting of hydrops. Color encoded M-mode overcomes some atrioventricular (AV) time intervals to further characterize
of these issues. In this, the M-mode cursor is optimized to the tachycardia.151 It is important to optimize Doppler gate
record atrial signals. The color Doppler gate is set over aorta as well as gain settings to allow for visualization of buried
or the LVOT and flow in the aorta (from ventricular ejection) events or A waves superimposed on ventricular ejection. This
is superimposed on the M-mode. (Figure 22D). The ability to technique can be used from other sites such as the pulmonary
obtain dual anatomic M-mode tracings on the newer machines vein and pulmonary artery and descending aorta and IVC.
may circumvent some of these issues (Figure 22C). The transmission of the ‘A’ reversal to the ductus venosus and
hepatic veins helps to identify atrial contraction sequence.
doppler evaluation Tissue velocity imaging using either annular Doppler or
simultaneous sampling of an atrium and ventricle has been
Pulsed Doppler recording of simultaneous inflow and outflow shown to permit reliable arrhythmia assessment.
signals in the LVOT can be used for characterizing the rhythm. Ultrasound also plays an important role in the assessment
The mitral valve ‘A’ wave results from atrial contraction and of fetal compensation to the arrhythmia. Hydrops is easy to
is followed by the systolic ejection wave in the left ventricular recognize, however assessment of fetal well-being in the
outflow from ventricular contraction (Figure 22A). However, prehydropic state may be challenging as current methods of
70 this method is not usable in the setting of high heart rates, assessment for heart failure are heavily dependent on Doppler
evaluations, which show baseline abnormalities while in • Premature atrial contractions 4
tachycardia. Persistence of abnormal venous Doppler in sinus • Premature ventricular contractions
rhythm, progressive valvular insufficiency and decreased • Mobitz type I or intermittent type II second degree block.
FEtal Cardiology
myocardial contractility may all provide clues. Atrial premature beats are fairly common in the late
second trimester and third trimester of pregnancy and are
Fetal electrocardiogram (FeCg) and often self-limiting. They may be conducted to the ventricle or
magnetocardiogram (FmCg) blocked with a resultant extra beat or skipped beat on Doppler
(Figure 23B). Persistent blocked atrial bigeminy will present
Fetal electrocardiogram (ECG) recordings are hampered by as fetal bradycardia (Figure 24B). It is important to assess the
low amplitude signals, especially from the atrium, secondary A-V relationship closely to rule out underlying conduction
to the insulating properties of vernix. Recent publications have defects (Figure 24). Most are self-limiting, however, there
outlined its use in a clinical setting for rhythm analysis but in is a 2 to 3 percent risk for sustained tachycardia especially
limited settings.152,153 Fetal magnetocardiogram, which involves in those with multiple or frequent blocked extrasystoles with
processing of the magnetic signals that go hand in hand with a resultant low heart rate.157 Hence, management includes
electrical signals, has been successfully applied to the study weekly, auscultation of the fetal heart in an outpatient till
of fetal rhythm and has provided valuable insights into the resolution and for any tachycardia. If they persist to term,
electrophysiological assessment of fetal arrhythmias; especially then a neonatal EKG is recommended to assess for underlying
those associated with abnormal repolarization.154–156 However, pre-excitation.
it is currently available only at a few centers worldwide and its Ventricular premature beats are occasionally seen in fetal life
lack of portability and need for a magnetically shielded room, and are diagnosed by a premature contraction of the ventricle
limits its applicability in the clinical arena. in the setting of a regular atrial rate (Figure 23C). Though they
are often benign, they may occur in the setting of increased
types of arrhythmias myocardial irritability as with myocarditis, tumors or long QT
syndrome and these should be ruled out on the basis of a full
echocardiographic evaluation and detailed history. Postnatal
Irregular Rhythms
evaluation is recommended with a baseline ECG.
These are common and usually noted in the obstetric office as Disorders of A-V conduction may present with an irregular
either extra beats or skipped beats. Causes include: rhythm. In Mobitz type I block, there is gradual prolongation
a C
Figures 23a to C: Superior vena cava/aorta (SVC-Ao) tracings in two fetuses with ectopic beats: A. 2D image showing a pulse Doppler sample
gate over the SVC and aorta to obtain simultaneous tracings; B. Conducted atrial ectopy. Atrial beats are denoted by arrows, solid arrows
denoting sinus beats and dashed arrows ectopic or early beats. Atrial ectopic beat (dashed arrow, a’) results in early ventricular beat (V); C.
Ventricular ectopic beats. Regular atrial rhythm is noted (solid arrows), however, ventricular rhythm is irregular secondary to ventricular ectopic
beats (V’); Solid arrows denote sinus atrial beats, dashed arrows and a’ denote early/ectopic atrial beats, V ventricular ejection and V’ premature 71
or early ventricular ejection
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b
C
Figures 24a to C: M-mode tracings from three fetuses with irregular rhythm: A. Fetal bradycardia secondary to 2:1 Mobitz type II block. Atrial
rhythm is regular and every other atrial impulse (arrow) results in a ventricular contraction (V); B. Fetal bradycardia secondary to blocked atrial
bigeminy. Every other atrial beat (arrow) is premature and is blocked (dashed arrows). Ventricular ejection results in flow in the aorta (E); C. Color
mode demonstrating Mobitz type I block. Arrows denote gradual prolongation of conduction time from atrial contraction to ventricular ejection (E)
and a non-conducted atrial impulse (dashed arrow)
of the mechanical PR interval culminating with a non- accessory pathway (AVRT) or nodal re-entry (AVNRT)
conducted atrial impulse (Figure 24C). In intermittent Mobitz accounting for about 70 percent of cases. Heart rates are
type II second degree heart block, the baseline mechanical typically in the 220 to 280 BPM range, with sudden onset and
PR interval is stable (normal or prolonged) but occasional rapid termination of tachycardia. SVC/Ao tracings show a
atrial impulses are non-conducted. This should prompt an short VA interval due to rapid depolarization of the atrium via
evaluation for presence of maternal SSA/SSB antibodies and the accessory connection (Figure 25A). Medications that affect
for familial channelopathy. This has occasionally been reported the nodal refractory period or the pathway characteristics are
in otherwise normal pregnancies with a good prognosis in often effective in termination of tachycardia. At birth about 10
general.158–160 percent will have Wolff–Parkinson–White syndrome (WPW).
The presence of a long VA interval indicates either an ectopic
Fetal tachycardia atrial focus or permanent junctional reciprocating tachycardia
(PJRT) (Figure 25B). PJRT can be incessant and often requires
Fetal tachycardia is diagnosed at ventricular rates greater polydrug therapy for control.
than 180 to 200 BPM. Associated CHD may be seen in about Atrial flutter is characterized by much faster atrial rates in
10 to 12 percent cases. A broad classification based on A-V the range of 350 to 500 minute with ventricular rates in 180 to
relationships includes: 250 range in the setting of 2 or 3 : 1 conduction (Figure 25C).
• Sinus tachycardia Ventricular response may be irregular. Initiation of drug therapy
• Supraventricular tachycardia with 1 : 1 A-V relation may result in abrupt drop in fetal heart rate due to high grade
• Atrial flutter AV block and is often mistaken for fetal distress resulting in
• Ventricular tachycardia. an emergency cesarean or mistaken for sinus tachycardia
Sinus tachycardia with heart rates greater than 180 BPM depending on ventricular rates. A quick evaluation by bedside
may result from a variety of conditions such as maternal ultrasound will clarify the situation. A third of the cases may
pyrexia, hyperthyroidism, fetal anemia, etc. It is characterized coexist with supraventricular tachycardia (SVT) in the setting
by 1 : 1 A-V relationship, long VA interval and a variable heart of an accessory connection.161,162
rate that gradually increases and decreases. Ventricular tachycardia or junctional ectopic tachycardia
Supraventricular tachycardia includes different types of is characterized by a ventricular rate that is greater than the
tachycardia with 1 : 1 A-V relationship. The most common atrial rate. The atrial rate is usually normal with a ventricular
72 mechanism is atrioventricular re-entry either along an rate ranging from 160 to 300 BPM. These are rare, but
4
FEtal Cardiology
a
C
Figures 25a to C: Superior vena cava and aorta tracings in three fetuses with tachy cardia. Arrows denote atrial contraction, V = Ventricular ejection.
Ventriculoatrial interval is measured from beginning of aortic flow to beginning of atrial flow reversal and atrioventricular time interval from beginning
of atrial flow reversal to beginning of next ventricular ejection; and is denoted by parallel lines. A. Short VA tachycardia. Note: Retrograde atrial wave
buried at the end of aortic flow (V); B. Long VA tachycardia in a fetus with atrial ectopic tachycardia; C. Atrial flutter with 2:1 conduction. A ventricular
ejection is present for every two atrial beats
may be seen in the setting of myocarditis, tumors, familial cardiac function in sinus rhythm and those with structural heart
channelopathy such as long QT syndrome (LQTS) as well as disease.165–167 Options include close observation, transplacental
immune-mediated heart block. It is not possible to characterize drug therapy and if that fails or in setting of hydrops, direct
ventricular repolarization abnormalities by ultrasound and this fetal therapy may be considered. Preterm delivery is avoided if
requires fetal ECG or magnetocardiography (MCG) to define the possible except if the fetus fails therapy and is of a sufficiently
fetal QTc.163–164 advanced gestational age and there is a clear advantage to
therapeutic options postdelivery.
management Medications that have been used for transplacental therapy
of tachyarrhythmia include digoxin, flecainide, sotalol,
The management of fetal tachycardia varies from center to amiodarone, propranolol, and propafenone, procainamide
center. General guidelines are presented here (Figure 26). and verapamil in the past.168 Most SVT can be successfully
Management options depend on the gestational age at diagnosis, managed by transplacental therapy. In the absence of hydrops
the frequency of tachycardia intermittent versus incessant, most centers will initiate therapy with digoxin which has
mechanism of tachycardia, presence or absence of hydrops and reported success rate of 60 to 80 percent in absence of hydrops
maternal and fetal well-being. Hydrops may result in upto 50 though therapeutic efficacy drops in setting of hydrops.169,170
percent of cases and risk increases with incessant tachycardia Digoxin is often used for its beneficial effects on fetal heart
(>50% time), younger gestation age at onset, diminished function. The second line of medications includes flecainide 73
http://vip.persianss.ir
1
Embryo to thE NEoNatE
Figure 26: Potential algorithm for the diagnosis and management of fetal tachycardia. 1. Presence or absence of suspicion for LQTS based
on history and FMCG/FECG if available. 2. Any of the drugs listed may be used with or without magnesium. Both sotalol and flecainide has
been used as first line or second line therapy with some studies suggesting better efficacy of sotalol for fetal atrial flutter. AET = Atrial ectopic
tachycardia; AF = Atrial flutter; A-V = Atrioventricular relationship; CAT = Chaotic atrial tachycardia; LQTS = Long QT syndrome; PJRT =
Paroxysmal reciprocating tachycardia; SVT = Supraventricular tachycardia includes both atrioventricular re-entry (AVRT) and atrioventricular
nodal re-entry tachycardia (AVNRT); V-T = Ventricular tachycardia—implies absence or presence of.
or sotalol with success rates approaching 60 to 85 percent A cardiology assessment of the mother to look for contrain-
and in some centers amiodarone. Studies suggest comparable dications to therapy, as well as monitoring for adverse effects
efficacy of both with flecainide having better efficacy with of the medications is critical. This involves multidisciplinary
SVT and sotalol with flutter.171–178 Direct fetal therapy care involving the perinatologist, pediatric cardiologist and
is limited to fetuses with poor response to transplacental adult cardiologist to help coordinate care and monitoring of
medications in setting of heart failure and prematurity. The mother and fetus.
risk of adverse outcomes and fetal mortality approaches 15
to 30 percent167,171 in setting of hydrops and 0 to 10 percent Fetal BradyCardIa
without.167,170,179 Other morbidities include risk for cerebral
injury and also prematurity.167,176,180 Upto two-third of Fetal bradycardia is defined as a persistent fetal heart rate of
cases may have recurrence of arrhythmia in the neonatal less than 110 BPM. Transient fetal bradycardia is often seen
period. Cases of atrial flutter have low recurrence rates post during ultrasound evaluations and demonstrates a brisk return
cardio version in the neonatal period, unless associated with to normal heart rates with release of pressure. Differential
underlying pre-excitation.151,167 diagnosis of fetal bradycardia includes:
Ventricular arrhythmias are rare and when incessant • Sinus bradycardia
have been managed with transplacental administration of • Blocked atrial bigeminy
74 magnesium, lidocaine, mexiletine, beta-blockers and amiod- • 2 : 1 atrioventricular block
arone.148,181 • Complete heart block.
4
FEtal Cardiology
a b
Figures 27a and b: Left atrial isomerism with complete heart block: A. 2D image with common atrioventricular valve separating the atrium (A)
and ventricle (V). The ventricular walls are thick and non-compacted. A pericardial effusion (E) is present; B. Simultaneous Doppler in descending
aorta and azygos vein demonstrating complete heart block along with sinus bradycardia. The atrial rate (A) was 110 with a ventricular rate (V)
about 55 and the two are dissociated as evidenced by varying A to V relation.
Sinus bradycardia demonstrates 1:1 AV conduction in evolved and suggests a generalized myocardial inflammation.
the setting of a slow atrial rate. Sinus bradycardia may be Findings reported include patchy areas of increased
seen in the setting of left atrial isomerism. In the setting of echogenicity, atrial endocardial fibroelastosis, valvular
a normal heart it may be associated with channelopathies insufficiency, chordal rupture, tachyarrhythmia including
as in SCN5A mutation, LQTS and in setting of maternal junctional tachycardia and torsade and sinus bradycardia
SSA/SSB antibodies, sick sinus syndrome and IUGR in and heart defects.186–189 Hydrops may result in setting of
fetus.148,159,182 Sinus bradycardia in setting of LQTS in fetus low non-reactive FHR below 50 BPM as well as myocardial
may be subtle with mean heart rates just below the 3 percent dysfunction.158,185,190 Once set CHB is generally thought to
in the 120 to 100 range in late gestation.183 In blocked atrial be irreversible even with steroid therapy with rare cases of
bigeminy (BAB) every other beat is an atrial ectopic beat that reversal being noted.191,192 In contrast, second degree heart
is non-conducted to the ventricles and the resultant ventricular block may show stabilization or rarely reversal.193 Recent
rate is usually slower than in sinus bradycardia (Figure 24B). data suggests that CHB may set in suddenly and the finding
It is usually associated with a good prognosis. of PR prolongation to ≥ 3 Z scores is not predictive for onset
Complete or third degree AV block presents with a of CHB.194,195
regular atrial rate and slow ventricular rate in the setting of
AV dissociation (Figures 27A and B). Second degree AV management oF autoImmune heart BloCk
block presents with a regular or irregular rhythm, while first
degree AV block manifests a regular rhythm with a prolonged Optimum evaluation schedule for fetuses at risk is not
mechanical PR interval. Isolated conduction abnormalities entirely clear. Many centers will offer weekly or biweekly
have been reported in setting of a normal heart.160 Complete monitoring of cardiac function and mechanical PR interval in
AV block is seen in the setting of CHD or with a structurally setting of maternal antibodies to SSA/SSB through 24 or 26
normal conduction system. Associated congenital heart defects weeks.196,197 Evaluation should include assessment for function
include left atrial isomerism and congenitally corrected and valvular insufficiency. Pharmacotherapy includes use of
transposition of the great vessels. Prognosis remains very poor beta- agonists such as terbutaline to augment fetal ventricular
in the setting of associated isomerism with only a 10 percent rates below 55 BPM, dexamethasone or beclomethasone to
survival in this setting.158,184 Therapy in these cases is generally limit inflammation and ongoing damage and intravenous IVIG
ineffective and includes use of beta agonists to increase fetal in an attempt to decrease circulating antibodies.168,189,190,193,
heart rate and also digoxin to improve contractility.185 196,198,199 Antenatal steroid therapy has associated risks of
The risk for immune mediated heart block is about 2 to oligohydramnios, neurologic concerns in the developing brain
3 percent in setting of maternal SSA and/or SSB antibodies. and maternal glucose intolerance. Indications are not clear, but
This risk increases to about 16 to 20 percent in setting of it is suggested that steroid therapy be reserved for cases with
a prior affected child suggesting that the cardiac effects are progressive heart block, evidence of endocardial fibroelastosis,
secondary to an interaction between environmental factors valvular insufficiency myocardial dysfunction or ongoing
with positive antibody status. The risk is highest between 16 features of heart failure. IVIG has been used in some fetuses
to 26 weeks of gestation, but CHB may be detected beyond non-responsive to steroids. Prophylactic IVIG given through
this time period and progression in postnatal period has been pregnancy in high-risk pregnancies did not prevent CHB in
reported. The spectrum of immune medicated disease has doses used.200–202 Survival in the setting of immune mediated 75
http://vip.persianss.ir
1
Embryo to thE NEoNatE
Figure 28: Potential algorithm for diagnosis and management of fetal bradycardia: AV = Atrioventricular, (-) denotes absence and (+) presence of
congenital heart disease (CHD); LQTS = Long QT syndrome; IVIG = Intravenous immunoglobulin. 1. Assessment for long QT syndrome includes
a detailed family history, parental ECG and evaluation of fetus with FMCG/FECG where available. 2. Steroids used include dexamethasone or
beclomethasone
complete heart block has improved from around 70 percent to and it is important that regional programs dedicated to local
now greater than 90 percent on recent reports.196,203 Figure 28 sonographer training and support be developed. Hand-in-
outlines a general approach to the evaluation and management hand with the technological and therapeutic advances, it is
of fetal bradycardia. important to keep a focus on ethical issues, which are unique
in this setting, with the potential of harm not only to the
Future dIreCtIons mother and fetus, but in cases of twin gestation to all three of
them! 3D and 4D ultrasound will likely play a more prevalent
Ultrasound has significantly advanced our understanding of role in remote diagnosis of CHD and assessment of cardiac
fetal cardiovascular physiology. Recent work with the use of function.41,44
fetal ECG and MCG point towards the presence of possible
fetal repolarization changes and potential arrhythmias in the Medicine is a science of uncertainty and an art of probability.
stressed fetus with underlying CHD.154–156 Technological —Sir William Osler
advances resulting in improvements in the ability to obtain
fetal ECG and MCG at the bedside are needed. It is likely aCknowledgments
that assessment of fetal cardiovascular status by ultrasound
will play a more important role in several non-cardiac I would like to thank our sonographers Tim Heiser, Janet
conditions as well as providing guidance for invasive Klobuchar and Barb Trampe, for their dedication and help with
procedures. Prenatal detection rates for CHD remains poor the image acquisition.
76
reFerenCes 16. Jouannic JM, Thieulin AC, Bonnet D, et al. Measurement of
nuchal translucency for prenatal screening of congenital heart
4
1. Hoffman JI, Kaplan S. The incidence of congenital heart defects: a population-based evaluation. Prenat Diagn. 2011;
FEtal Cardiology
disease. J Am Coll Cardiol. 2002; 39:1890-1900. Epub 31:1264-9. Epub 2011/10/27.
2002/06/27. 17. Schwarzler P, Carvalho JS, Senat MV, et al. Screening for fetal
2. van der Linde D, Konings EE, Slager MA, et al. Birth aneuploidies and fetal cardiac abnormalities by nuchal translu-
prevalence of congenital heart disease worldwide: a systematic cency thickness measurement at 10-14 weeks of gestation as
review and meta-analysis. J Am Coll Cardiol. 2011; ; 58:2241- part of routine antenatal care in an unselected population. Br J
7. Epub 2011/11/15. Obstet Gynaecol. 1999; 106:1029-34. Epub 1999/10/16.
3. Pierpont ME, Basson CT, Benson DW Jr, et al. Genetic basis 18. Mogra R, Alabbad N, Hyett J. Increased nuchal translucency
for congenital heart defects: current knowledge: a scientific and congenital heart disease. Early Hum Dev. 2012; 88:
statement from the American Heart Association Congenital 261-7. Epub 2012/04/10.
Cardiac Defects Committee, Council on Cardiovascular Disease 19. Allan LD. The mystery of nuchal translucency. Cardiol Young.
in the Young: endorsed by the American Academy of Pediatrics. 2006; 16:11-7. Epub 2006/02/04.
Circulation. 2007; 115:3015-38. Epub 2007/05/24. 20. Bebbington M, Wilson RD, Johnson MP. Detection of
4. Reller MD, Strickland MJ, Riehle-Colarusso T, et al. Prevalence congenital heart disease in the first trimester of pregnancy.
of congenital heart defects in metropolitan Atlanta, 1998-2005. Progress in Pediatric Cardiology. 2006; 22:3-8.
J Pediatr. 2008; 153:807-13. Epub 2008/07/29. 21. Rychik J, Ayres N, Cuneo B, et al. American Society of
5. Bernier PL, Stefanescu A, Samoukovic G, et al. The challenge Echocardiography guidelines and standards for performance
of congenital heart disease worldwide: epidemiologic and of the fetal echocardiogram. J Am Soc Echocardiogr. 2004;
demographic facts. Seminars in thoracic and cardiovascular 17:803-10. Epub 2004/06/29.
surgery Pediatric cardiac surgery annual. 2010; 13:26-34. Epub 22. Pruetz JD, Sklansky M, Detterich J, et al. Twin-twin transfusion
2010/03/24. syndrome treated with laser surgery: postnatal prevalence of
6. Oyen N, Poulsen G, Boyd HA, et al. National time trends in congenital heart disease in surviving recipients and donors.
congenital heart defects, Denmark, 1977-2005. Am Heart J. Prenat Diagn. 2011; 31:973-7. Epub 2011/07/12.
2009; 157:467-73 e1. Epub 2009/03/03. 23. Manning N, Archer N. A study to determine the incidence of
7. Simpson LL. Indications for fetal echocardiography from a structural congenital heart disease in monochorionic twins.
tertiary-care obstetric sonography practice. J Clin Ultrasound. Prenat Diagn. 2006; 26:1062-4. Epub 2006/09/08.
2004; 32:123-8. Epub 2004/03/03. 24. Fesslova V, Brankovic J, Lalatta F, et al. Recurrence of
8. Friedberg MK, Silverman NH. Changing indications for fetal congenital heart disease in cases with familial risk screened
echocardiography in a University Center population. Prenat prenatally by echocardiography. Journal of pregnancy. 2011;
Diagn. 2004; 24:781-6. Epub 2004/10/27. 2011:368-067. Epub 2011/10/07.
9. Perri T, Cohen-Sacher B, Hod M, et al. Risk factors for cardiac 25. Oberhansli I, Extermann P, Jaggi E. Fetal echocardiography in
malformations detected by fetal echocardiography in a tertiary pregnancies of women with congenital heart disease-clinical
center. The journal of maternal-fetal and neonatal medicine : utility and limitations. Thorac Cardiovasc Surg. 2000; 48:323-
the official journal of the European Association of Perinatal 7. Epub 2001/01/06.
Medicine, the Federation of Asia and Oceania Perinatal 26. Cooper MJ, Enderlein MA, Dyson DC, et al. Fetal echocar-
Societies, the International Society of Perinatal Obstet. 2005; diography: retrospective review of clinical experience and an
17:123-8. Epub 2005/08/04. evaluation of indications. Obstet Gynecol. 1995; 86: 577-82.
10. Fishman SG, Pelaez LM, Baergen RN, et al. Carroll SJ. Epub 1995/10/01.
Parvovirus-mediated fetal cardiomyopathy with atrioven- 27. Stumpflen I, Stumpflen A, Wimmer M, et al. Effect of
tricular nodal disease. Pediatr Cardiol. 2011; 32:84-6. Epub detailed fetal echocardiography as part of routine prenatal
2010/10/12. ultrasonographic screening on detection of congenital heart
11. Ranucci-Weiss D, Uerpairojkit B, Bowles N, et al. Intrauterine disease. Lancet. 1996; 348:854-7. Epub 1996/09/28.
adenoviral infection associated with fetal non-immune 28. Achiron R, Glaser J, Gelernter I, et al. Extended fetal echocardio-
hydrops. Prenat Diagn. 1998; 18:182-5. Epub 1998/03/27. graphic examination for detecting cardiac malformations in low
12. Allan LD, Sharland GK, Chita SK, et al. Chromosomal risk pregnancies. BMJ. 1992; 304:671-4. Epub 1992/03/14.
anomalies in fetal congenital heart disease. Ultrasound Obstet 29. Sharland G. Routine fetal cardiac screening: what are we doing
Gynecol. 1991; 1:8-11. Epub 1991/01/01. and what should we do? Prenat Diagn. 2004; 24:1123-9. Epub
13. Hyett J, Perdu M, Sharland G, et al. Using fetal nuchal 2004/12/23.
translucency to screen for major congenital cardiac defects at 30. Pinto NM, Keenan HT, Minich LL, et al. Barriers to Prenatal
10-14 weeks of gestation: population based cohort study. BMJ. Detection of Congenital Heart Disease: A Population-Based
1999; 318:81-5. Epub 1999/01/08. Study. Ultrasound Obstet Gynecol. 2011. Epub 2011/10/15.
14. Makrydimas G, Sotiriadis A, Ioannidis JP. Screening perfor- 31. Friedberg MK, Silverman NH, Moon-Grady AJ, et al. Prenatal
mance of first-trimester nuchal translucency for major detection of congenital heart disease. J Pediatr. 2009; 155:26-
cardiac defects: a meta-analysis. Am J Obstet Gynecol. 2003; 31, e1. Epub 2009/04/28.
189:1330-5. Epub 2003/11/25. 32. Michelfelder EC, Cnota JF. Prenatal diagnosis of congenital
15. Simpson LL, Malone FD, Bianchi DW, et al. Nuchal heart disease in an era of near-universal ultrasound screening:
translucency and the risk of congenital heart disease. Obstet room for improvement. J Pediatr. 2009; 155:9-11. Epub
77
Gynecol. 2007; 109:376-83. Epub 2007/02/03. 2009/06/30.
http://vip.persianss.ir
1 33. Sklansky M. Current guidelines for fetal echocardiography:
time to raise the bar. J Ultrasound Med. 2011; 30:284-6; author
49. Schneider C, McCrindle BW, Carvalho JS, et al. Development
of Z-scores for fetal cardiac dimensions from echocardiography.
reply 6. Epub 2011/01/27. Ultrasound Obstet Gynecol. 2005; 26:599-605. Epub
Embryo to thE NEoNatE
34. Sklansky MS, Berman DP, Pruetz JD, et al. Prenatal screening 2005/10/29.
for major congenital heart disease: superiority of outflow tracts 50. Shapiro I, Degani S, Leibovitz Z, et al. Fetal cardiac measure-
over the 4-chamber view. J Ultrasound Med. 2009; 28:889-99. ments derived by transvaginal and transabdominal cross-
Epub 2009/06/24. sectional echocardiography from 14 weeks of gestation to term.
35. Sharland GK, Allan LD. Screening for congenital heart disease Ultrasound Obstet Gynecol. 1998; 12:404-18. Epub 1999/01/26.
prenatally. Results of a 2 1/2-year study in the South East 51. Lee W, Riggs T, Amula V, et al. Fetal echocardiography: z-score
Thames Region. Br J Obstet Gynaecol. 1992; 99:220-5. Epub reference ranges for a large patient population. Ultrasound
1992/03/01. Obstet Gynecol. 2010; 35:28-34. Epub 2009/12/17.
36. Hunter S, Heads A, Wyllie J, et al. Prenatal diagnosis of 52. Pasquini L, Mellander M, Seale A, et al. Z-scores of the fetal
congenital heart disease in the northern region of England: aortic isthmus and duct: an aid to assessing arch hypoplasia.
benefits of a training programme for obstetric ultrasonographers. Ultrasound Obstet Gynecol. 2007; 29:628-33. Epub 2007/05/04.
Heart. 2000; 84:294-8. Epub 2000/08/24. 53. Peterson RE, Levi DS, Williams RJ, et al. Echocardiographic
37. Chang RK, Gurvitz M, Rodriguez S. Missed diagnosis of predictors of outcome in fetuses with pulmonary atresia with
critical congenital heart disease. Arch Pediatr Adolesc Med. intact ventricular septum. J Am Soc Echocardiogr. 2006;
2008; 162:969-74. Epub 2008/10/08. 19:1393-400. Epub 2006/11/14.
38. Volpe P, Ubaldo P, Volpe N, et al. Fetal cardiac evaluation 54. Salvin JW, McElhinney DB, Colan SD, et al. Fetal tricuspid
at 11-14 weeks by experienced obstetricians in a low-risk valve size and growth as predictors of outcome in pulmonary
population. Prenat Diagn. 2011; 31:1054-61. Epub 2011/07/30. atresia with intact ventricular septum. Pediatrics. 2006;
39. Westin M, Saltvedt S, Bergman G, et al. Routine ultrasound ex- 118:e415-20. Epub 2006/08/03.
amination at 12 or 18 gestational weeks for prenatal detection 55. Makikallio K, McElhinney DB, Levine JC, et al. Fetal aortic
of major congenital heart malformations? A randomised con- valve stenosis and the evolution of hypoplastic left heart
trolled trial comprising 36,299 fetuses. BJOG: an international syndrome: patient selection for fetal intervention. Circulation.
journal of obstetrics and gynaecology. 2006; 113:675-82. Epub 2006; 113:1401-5. Epub 2006/03/15.
2006/05/20. 56. Matsui H, Mellander M, Roughton M, et al. Morphological and
40. Persico N, Moratalla J, Lombardi CM, et al. Fetal echocardi- physiological predictors of fetal aortic coarctation. Circulation.
ography at 11-13 weeks by transabdominal high-frequency ul- 2008; 118:1793-801. Epub 2008/10/15.
trasound. Ultrasound Obstet Gynecol. 2011; 37:296-301. Epub 57. Simpson JM, Cook A. Repeatability of echocardiographic
2011/01/14. measurements in the human fetus. Ultrasound Obstet Gynecol.
41. Yagel S, Cohen SM, Rosenak D, et al. Added value of three-/ 2002; 20:332-9. Epub 2002/10/18.
four-dimensional ultrasound in offline analysis and diagnosis 58. Feit LR, Copel JA, Kleinman CS. Foramen ovale size in
of congenital heart disease. Ultrasound Obstet Gynecol. 2011; the normal and abnormal human fetal heart: an indicator of
37:432-7. Epub 2010/10/30. transatrial flow physiology. Ultrasound Obstet Gynecol. 1991;
42. Goncalves LF, Lee W, Chaiworapongsa T, et al. Four-dimen- 1:313-9. Epub 1991/09/01.
sional ultrasonography of the fetal heart with spatiotemporal 59. Vida VL, Bacha EA, Larrazabal A, et al. Hypoplastic left
image correlation. Am J Obstet Gynecol. 2003; 189:1792-802. heart syndrome with intact or highly restrictive atrial septum:
Epub 2004/01/08. surgical experience from a single center. Ann Thorac Surg.
43. DeVore GR, Sklansky MS. Three-dimensional imaging of the 2007; 84:581-5; discussion 6. Epub 2007/07/24.
fetal heart: Current applications and future directions. Progress 60. Vlahos AP, Lock JE, McElhinney DB, et al. ME. Hypoplastic
in Pediatric Cardiology. 2006; 22:9-29. left heart syndrome with intact or highly restrictive atrial
44. Espinoza J, Lee W, Comstock C, et al. Collaborative study septum: outcome after neonatal transcatheter atrial septostomy.
on 4-dimensional echocardiography for the diagnosis of fetal Circulation. 2004; 109:2326-330. Epub 2004/05/12.
heart defects: the COFEHD study. J Ultrasound Med. 2010; 61. Divanovic A, Hor K, Cnota J, et al. Prediction and perinatal
29:1573-80. Epub 2010/10/23. management of severely restrictive atrial septum in fetuses
45. Messing B, Cohen SM, Valsky DV, et al. Fetal cardiac ventricle with critical left heart obstruction: clinical experience using
volumetry in the second half of gestation assessed by 4D ultra- pulmonary venous Doppler analysis. J Thorac Cardiovasc
sound using STIC combined with inversion mode. Ultrasound Surg. 2011; 141:988-94. Epub 2010/12/07.
Obstet Gynecol. 2007; 30:142-51. Epub 2007/06/15. 62. Donofrio MT, Bremer YA, Moskowitz WB. Diagnosis and
46. Cordes TM, O'Leary PW, Seward JB, et al. Distinguishing right management of restricted or closed foramen ovale in fetuses
from left: a standardized technique for fetal echocardiography. with congenital heart disease. Am J Cardiol. 2004; 94:1348-51.
J Am Soc Echocardiogr. 1994; 7:47-53. Epub 1994/01/01. Epub 2004/11/16.
47. Yagel S, Cohen SM, Achiron R. Examination of the fetal heart 63. Maeno YV, Kamenir SA, Sinclair B, et al. Prenatal Features of
by five short-axis views: a proposed screening method for Ductus Arteriosus Constriction and Restrictive Foramen Ovale
comprehensive cardiac evaluation. Ultrasound Obstet Gynecol. in d-Transposition of the Great Arteries. Circulation. 1999;
2001; 17:367-69. Epub 2001/06/16. 99:1209-14.
48. Sharland GK, Allan LD. Normal fetal cardiac measurements 64. Punn R, Silverman NH. Fetal predictors of urgent balloon atrial
derived by cross-sectional echocardiography. Ultrasound septostomy in neonates with complete transposition. J Am Soc
78
Obstet Gynecol. 1992; 2:175-81. Epub 1992/05/01. Echocardiogr. 2011; 24:425-30. Epub 2011/02/18.
65. Chintala K, Tian Z, Du W, et al. Fetal pulmonary venous
Doppler patterns in hypoplastic left heart syndrome:
80. Tometzki AJ, Suda K, Kohl T, et al. Accuracy of prenatal
echocardiographic diagnosis and prognosis of fetuses with
4
relationship to atrial septal restriction. Heart. 2008; 94:1446-9. conotruncal anomalies. J Am Coll Cardiol. 1999; 33:1696-701.
FEtal Cardiology
Epub 2007/10/10. Epub 1999/05/20.
66. Pitkanen OM, Hornberger LK, Miner SE, et al. Borderline left 81. Galindo A, Mendoza A, Arbues J, et al. Conotruncal anomalies
ventricles in prenatally diagnosed atrioventricular septal defect in fetal life: accuracy of diagnosis, associated defects and
or double outlet right ventricle: echocardiographic predictors outcome. Eur J Obstet Gynecol Reprod Biol. 2009; 146:55-60.
of biventricular repair. Am Heart J. 2006; 152:163 e1-7. Epub Epub 2009/06/02.
2006/07/11. 82. Sivanandam S, Glickstein JS, Printz BF, et al. Prenatal diagnosis
67. Huggon IC, Cook AC, Smeeton NC, et al. Atrioventricular of conotruncal malformations: diagnostic accuracy, outcome,
septal defects diagnosed in fetal life: associated cardiac and chromosomal abnormalities, and extracardiac anomalies. Am J
extra-cardiac abnormalities and outcome. J Am Coll Cardiol. Perinatol. 2006; 23:241-5. Epub 2006/04/21.
2000; 36:593-601. Epub 2000/08/10. 83. Yagel S, Arbel R, Anteby EY, et al. The three vessels and
68. Hornberger LK, Sahn DJ, Kleinman CS, et al. Tricuspid valve trachea view (3VT) in fetal cardiac scanning. Ultrasound
disease with significant tricuspid insufficiency in the fetus: Obstet Gynecol. 2002; 20:340-5. Epub 2002/10/18.
diagnosis and outcome. J Am Coll Cardiol. 1991; 17:167-73. 84. Vinals F, Heredia F, Giuliano A. The role of the three vessels
Epub 1991/01/01. and trachea view (3VT) in the diagnosis of congenital heart
69. Messing B, Porat S, Imbar T, et al. Mild tricuspid regurgitation: defects. Ultrasound Obstet Gynecol. 2003; 22:358-67. Epub
a benign fetal finding at various stages of pregnancy. 2003/10/07.
Ultrasound Obstet Gynecol. 2005; 26:606-9; discussion 10. 85. Wu Q, Li M, Ju L, et al. Application of the 3-vessel view
Epub 2005/10/08. in routine prenatal sonographic screening for congenital
70. Respondek ML, Kammermeier M, Ludomirsky A, et al. The heart disease. J Ultrasound Med. 2009; 28:1319-24. Epub
prevalence and clinical significance of fetal tricuspid valve 2009/09/26.
regurgitation with normal heart anatomy. Am J Obstet Gynecol. 86. Escribano D, Herraiz I, Granados M, et al. Tetralogy of
1994; 171:1265-70. Epub 1994/11/01. Fallot: prediction of outcome in the mid-second trimester of
71. Berg C, Lachmann R, Kaiser C, et al. Prenatal diagnosis of pregnancy. Prenat Diagn. 2011; 31:1126-33. Epub 2011/09/20.
tricuspid atresia: intrauterine course and outcome. Ultrasound 87. Wertaschnigg D, Jaeggi M, Chitayat D, et al. Prenatal
Obstet Gynecol. 2010; 35:183-90. Epub 2010/01/27. Diagnosis and Outcome of Absent Pulmonary Valve
72. Roman KS, Fouron JC, Nii M, et al. Determinants of outcome in Syndrome: Contemporary Single Center Experience and
fetal pulmonary valve stenosis or atresia with intact ventricular Review of the Literature. Ultrasound Obstet Gynecol. 2012.
septum. Am J Cardiol. 2007; 99:699-703. Epub 2007/02/24. Epub 2012/05/19.
73. Gardiner HM, Belmar C, Tulzer G, et al. Morphologic and 88. Jouannic JM, Gavard L, Fermont L, et al. Sensitivity and
functional predictors of eventual circulation in the fetus specificity of prenatal features of physiological shunts to
with pulmonary atresia or critical pulmonary stenosis with predict neonatal clinical status in transposition of the great
intact septum. J Am Coll Cardiol. 2008; 51:1299-308. Epub arteries. Circulation. 2004; 110:1743-6. Epub 2004/09/15.
2008/03/29. 89. Sharland G, Tingay R, Jones A, et al. Atrioventricular
74. Lasa JJ, Tian ZY, Guo R, et al. Perinatal course of Ebstein's and ventriculoarterial discordance (congenitally corrected
anomaly and tricuspid valve dysplasia in the fetus. Prenat transposition of the great arteries): echocardiographic features,
Diagn. 2012; 32:245-51. Epub 2012/03/21. associations, and outcome in 34 fetuses. Heart. 2005; 91:1453-
75. Barre E, Durand I, Hazelzet T, et al. Anomaly and Tricuspid 8. Epub 2005/03/12.
Valve Dysplasia: Prognosis After Diagnosis In Utero. Pediatr 90. Paladini D, Volpe P, Marasini M, et al. Diagnosis,
Cardiol. 2012. Epub 2012/05/29. characterization and outcome of congenitally corrected
76. Vogel M, McElhinney DB, Wilkins-Haug LE, et al. Aortic transposition of the great arteries in the fetus: a multicenter
stenosis and severe mitral regurgitation in the fetus resulting in series of 30 cases. Ultrasound Obstet Gynecol. 2006; 27:
giant left atrium and hydrops: pathophysiology, outcomes, and 281-5. Epub 2006/02/18.
preliminary experience with pre-natal cardiac intervention. J 91. Lagopoulos ME, Manlhiot C, McCrindle BW, et al. Impact
Am Coll Cardiol. 2011; 57:348-55. Epub 2011/01/15. of prenatal diagnosis and anatomical subtype on outcome in
77. Rogers LS, Peterson AL, Gaynor JW, et al. Mitral valve dysplasia double outlet right ventricle. Am Heart J. 2010; 160:692-700.
syndrome: a unique form of left-sided heart disease. J Thorac Epub 2010/10/12.
Cardiovasc Surg. 2011; 142:1381-7. Epub 2011/07/15. 92. Swanson TM, Selamet Tierney ES, Tworetzky W, et al.
78. Weber RW, Ayala-Arnez R, Atiyah M, et al. Foetal Truncus arteriosus: diagnostic accuracy, outcomes, and impact
echocardiographic assessment of borderline small left of prenatal diagnosis. Pediatr Cardiol. 2009; 30:256-61. Epub
ventricles can predict the need for postnatal intervention. 2008/11/19.
Cardiol Young. 2012. pp. 1-9. Epub 2012/04/06. 93. Jung E, Won HS, Lee PR, et al. Clinical implication of isolated
79. McElhinney DB, Marshall AC, Wilkins-Haug LE, et al. right dominant heart in the fetus. Prenat Diagn. 2007; 27:695-
Predictors of technical success and postnatal biventricular 8. Epub 2007/05/19.
outcome after in utero aortic valvuloplasty for aortic stenosis 94. Jowett V, Aparicio P, Santhakumaran S, et al. Sonographic
with evolving hypoplastic left heart syndrome. Circulation. predictors of surgery in fetal coarctation of the aorta. Ultrasound
2009; 120:1482-90. Epub 2009/09/30. Obstet Gynecol. 2012. Epub 2012/03/31.
79
http://vip.persianss.ir
1 95. Head CE, Jowett VC, Sharland GK, et al. Timing of
presentation and postnatal outcome of infants suspected of
112. Bacha EA. Impact of fetal cardiac intervention on congenital
heart surgery. Seminars in thoracic and cardiovascular
having coarctation of the aorta during fetal life. Heart. 2005; surgery Pediatric cardiac surgery annual. 2011; 14:35-7. Epub
Embryo to thE NEoNatE
FEtal Cardiology
Perinat Med. 2001; 29:390-8. Epub 2001/11/29. rience. Prenat Diagn. 2004; 24:1068-80. Epub 2004/12/22.
132. Baschat AA. Examination of the fetal cardiovascular system. 149. Serra V, Bellver J, Moulden M, et al. Computerized analysis of
Seminars in fetal & neonatal medicine. 2011; 16:2-12. Epub normal fetal heart rate pattern throughout gestation. Ultrasound
2010/09/25. Obstet Gynecol. 2009; 34:74-9. Epub 2009/06/03.
133. Baschat AA, Harman CR. Venous Doppler in the assessment 150. Park MI, Hwang JH, Cha KJ, et al. Computerized analysis of
of fetal cardiovascular status. Curr Opin Obstet Gynecol. 2006; fetal heart rate parameters by gestational age. Int JGynaecol
18:156-63. Epub 2006/04/08. Obstet. 2001; 74:157-64. Epub 2001/08/15.
134. Gembruch U, Meise C, Germer U, et al. Venous Doppler 151. Fouron JC, Fournier A, Proulx F, et al. Management of fetal
ultrasound in 146 fetuses with congenital heart disease. tachyarrhythmia based on superior vena cava/aorta Doppler
Ultrasound Obstet Gynecol. 2003; 22:345-50. Epub flow recordings. Heart. 2003; 89:1211-6. Epub 2003/09/17.
2003/10/07. 152. Fujimoto Y, Matsumoto T, Honda N, et al. Prenatal diagnosis of
135. Bianco K, Small M, Julien S, et al. Second-trimester ductus long QT syndrome by non-invasive fetal electrocardiography. J
venosus measurement and adverse perinatal outcome in fetuses Obstet Gynaecol Res. 2009; 35:555-61. Epub 2009/06/17.
with congenital heart disease. J Ultrasound Med. 2006; 25:979- 153. Graatsma EM, Jacod BC, van Egmond LA, et al. Fetal
82; quiz 83. Epub 2006/07/28. electrocardiography: feasibility of long-term fetal heart rate
136. Berg C, Kremer C, Geipel A, et al. Ductus venosus blood recordings. BJOG: an international journal of obstetrics
flow alterations in fetuses with obstructive lesions of the right and gynaecology. 2009; 116:334-7; discussion 7-8. Epub
heart. Ultrasound Obstet Gynecol. 2006; 28:137-42. Epub 2008/12/17.
2006/07/11. 154. Strasburger JF, Cheulkar B, Wakai RT. Magnetocardiography
137. Manning N, Archer N. Fetal pulmonary venous Doppler flow for fetal arrhythmias. Heart rhythm : the official journal of the
patterns in hypoplastic left heart syndrome. Heart. 2008; Heart Rhythm Society. 2008; 5:1073-6. Epub 2008/05/20.
94:1374-5. Epub 2008/10/22. 155. Zhao H, Strasburger JF, Cuneo BF, et al. Fetal cardiac
138. Michelfelder E, Gomez C, Border W, et al. Predictive value of repolarization abnormalities. Am J Cardiol. 2006; 98:491-6.
fetal pulmonary venous flow patterns in identifying the need for Epub 2006/08/09.
atrial septoplasty in the newborn with hypoplastic left ventricle. 156. Cuneo BF, Strasburger JF, Wakai RT. Magnetocardiography in
Circulation. 2005; 112:2974-9. Epub 2005/11/02. the evaluation of fetuses at risk for sudden cardiac death before
139. Baschat AA, Gembruch U, Harman CR. The sequence of birth. J Electrocardiol. 2008; 41:116 e1-6. Epub 2008/03/11.
changes in Doppler and biophysical parameters as severe fetal 157. Vergani P, Mariani E, Ciriello E, et al. Fetal arrhythmias:
growth restriction worsens. Ultrasound Obstet Gynecol. 2001; natural history and management. Ultrasound Med Biol. 2005;
18:571-7. Epub 2002/02/15. 31:1-6. Epub 2005/01/18.
140. Society for Maternal-Fetal Medicine Publications C, Berkley 158. Lopes LM, Tavares GM, Damiano AP, et al. Perinatal outcome
E, Chauhan SP, et al. Doppler assessment of the fetus with of fetal atrioventricular block: one-hundred-sixteen cases from
intrauterine growth restriction. Am J Obstet Gynecol. 2012; a single institution. Circulation. 2008; 118:1268-75. Epub
206:300-8. Epub 2012/04/03. 2008/09/04.
141. Guorong L, Shaohui L, Peng J, et al. Cerebrovascular blood 159. Lin MT, Hsieh FJ, Shyu MK, et al. Postnatal outcome of fetal
flow dynamic changes in fetuses with congenital heart disease. bradycardia without significant cardiac abnormalities. Am
Fetal Diagn Ther. 2009; 25:167-72. Epub 2009/03/19. Heart J. 2004; 147:540-4. Epub 2004/03/05.
142. Berg C, Gembruch O, Gembruch U, et al. Doppler indices 160. Chang YL, Hsieh PC, Chang SD, et al. Perinatal outcome of fetus
of the middle cerebral artery in fetuses with cardiac defects with isolated congenital second degree atrioventricular block
theoretically associated with impaired cerebral oxygen without maternal anti-SSA/Ro-SSB/La antibodies. Eur J Obstet
delivery in utero: is there a brain-sparing effect? Ultrasound Gynecol Reprod Biol. 2005; 122:167-71. Epub 2005/10/13.
Obstet Gynecol. 2009; 34:666-72. Epub 2009/12/03. 161. Jaeggi E, Fouron JC, Drblik SP. Fetal atrial flutter: diagnosis,
143. Kaltman JR, Di H, Tian Z, et al. Impact of congenital heart clinical features, treatment, and outcome. J Pediatr. 1998;
disease on cerebrovascular blood flow dynamics in the fetus. 132:335-9. Epub 1998/03/20.
Ultrasound Obstet Gynecol. 2005; 25:32-6. Epub 2004/12/14. 162. Simpson JM, Sharland GK. Fetal tachycardias: management
144. Huhta JC, Paul JJ. Doppler in fetal heart failure. Clin Obstet and outcome of 127 consecutive cases. Heart. 1998; 79:576-
Gynecol. 2010; 53:915-29. Epub 2010/11/05. 81. Epub 1999/03/17.
145. Wieczorek A, Hernandez-Robles J, Ewing L, et al. Prediction of 163. Cuneo BF, Ovadia M, Strasburger JF, et al. Prenatal diagnosis
outcome of fetal congenital heart disease using a cardiovascular and in utero treatment of torsades de pointes associated with
profile score. Ultrasound Obstet Gynecol. 2008; 31:284-8. congenital long QT syndrome. Am J Cardiol. 2003; 91:1395-8.
Epub 2008/02/07. Epub 2003/05/28.
146. Hofstaetter C, Hansmann M, Eik-Nes SH, et al. A cardiovascular 164. Cuneo BF, Strasburger JF, Wakai RT, et al. Conduction system
profile score in the surveillance of fetal hydrops. The journal of disease in fetuses evaluated for irregular cardiac rhythm. Fetal
maternal-fetal and neonatal medicine: the official journal of the Diagn Ther. 2006; 21:307-13. Epub 2006/04/08.
European Association of Perinatal Medicine, the Federation of 165. Cuneo BF, Strasburger JF. Management strategy for fe-
Asia and Oceania Perinatal Societies, the International Society tal tachycardia. Obstet Gynecol. 2000; 96:575-81. Epub
81
of Perinatal Obstet. 2006; 19:407-13. Epub 2006/08/23. 2000/09/27.
http://vip.persianss.ir
1 166. Naheed ZJ, Strasburger JF, Deal BJ, et al. Fetal tachycardia:
mechanisms and predictors of hydrops fetalis. J Am Coll
nationwide questionnaire survey in Japan. Circulation Arrhyth-
mia and electrophysiology. 2010; 3:10-7. Epub 2009/12/10.
Cardiol. 1996; 27:1736-40. Epub 1996/06/01. 184. Jaeggi ET, Hornberger LK, Smallhorn JF, et al. Prenatal
Embryo to thE NEoNatE
167. Moodley S, Sanatani S, Potts JE, et al. Postnatal Outcome in diagnosis of complete atrioventricular block associated with
Patients With Fetal Tachycardia. Pediatr Cardiol. 2012. Epub structural heart disease: combined experience of two tertiary
2012/05/29. care centers and review of the literature. Ultrasound Obstet
168. Strasburger JF, Wakai RT. Fetal cardiac arrhythmia detection Gynecol. 2005; 26:16-21. Epub 2005/06/07.
and in utero therapy. Nature reviews Cardiology. 2010; 7:277- 185. Zhao H, Cuneo BF, Strasburger JF, et al. Electrophysiological
90. Epub 2010/04/27. characteristics of fetal atrioventricular block. J Am Coll
169. Srinivasan S, Strasburger J. Overview of fetal arrhythmias. Cardiol. 2008; 51:77-84. Epub 2008/01/05.
Curr Opin Pediatr. 2008; 20:522-31. Epub 2008/09/11. 186. Cuneo BF, Strasburger JF, Niksch A, et al. An expanded
170. Krapp M, Kohl T, Simpson JM, et al. Review of diagnosis, phenotype of maternal SSA/SSB antibody-associated fetal
treatment, and outcome of fetal atrial flutter compared with cardiac disease. The journal of maternal-fetal and neonatal
supraventricular tachycardia. Heart. 2003; 89:913-7. Epub medicine: the official journal of the European Association
2003/07/16. of Perinatal Medicine, the Federation of Asia and Oceania
171. Jaeggi ET, Carvalho JS, De Groot E, et al. Comparison of Perinatal Societies, the International Society of Perinatal
transplacental treatment of fetal supraventricular tachyarrhyth- Obstet. 2009; 22:233-8. Epub 2009/03/31.
mias with digoxin, flecainide, and sotalol: results of a nonran- 187. Hornberger LK, Al Rajaa N. Spectrum of cardiac involvement
domized multicenter study. Circulation. 2011; 124:1747-54. in neonatal lupus. Scand J Immunol. 2010; 72:189-97. Epub
Epub 2011/09/21. 2010/08/11.
172. van den Heuvel F, Bink-Boelkens MT, du Marchie Sarvaas 188. Cuneo BF, Fruitman D, Benson DW, et al. Spontaneous rupture
GJ, et al. Drug management of fetal tachyarrhythmias: are we of atrioventricular valve tensor apparatus as late manifestation
ready for a systematic and evidence-based approach? Pacing of anti-Ro/SSA antibody-mediated cardiac disease. Am J
Clin Electrophysiol. 2008; 31:S54-7. Epub 2008/03/25. Cardiol. 2011; 107:761-6. Epub 2011/01/21.
173. Sonesson SE, Fouron JC, Wesslen-Eriksson E, et al. Foetal 189. Krishnan A, Pike JI, Donofrio MT. Prenatal Evaluation and
supraventricular tachycardia treated with sotalol. Acta Paediatr. Management of Fetuses Exposed to Anti-SSA/Ro Antibodies.
1998; 87:584-7. Epub 1998/06/26. Pediatr Cardiol. 2012. Epub 2012/05/23.
174. Shah A, Moon-Grady A, Bhogal N, et al. Effectiveness of sotalol 190. Fesslova V, Vignati G, Brucato A, et al. The impact of treatment
as first-line therapy for fetal supraventricular tachyarrhythmias. of the fetus by maternal therapy on the fetal and postnatal
Am J Cardiol. 2012; 109:1614-8. Epub 2012/03/27. outcomes for fetuses diagnosed with isolated complete
175. Oudijk MA, Michon MM, Kleinman CS, et al. Sotalol in the atrioventricular block. Cardiol Young. 2009; 19:282-90. Epub
treatment of fetal dysrhythmias. Circulation. 2000; 101: 2721- 2009/04/23.
6. Epub 2000/06/14. 191. Adams LL, Gungor S, Salim M, et al. Regression of fetal
176. Lulic Jurjevic R, Podnar T, Vesel S. Diagnosis, clinical features, heart block and myocardial echogenicity with steroid therapy
management, and post-natal follow-up of fetal tachycardias. in maternal Sjogren's syndrome. Ultrasound Obstet Gynecol.
Cardiol Young. 2009; 19:486-93. Epub 2009/08/20. 2008; 32:839-40. Epub 2008/10/08.
177. Krapp M, Baschat AA, Gembruch U, et al. Flecainide in the 192. Mevorach D, Elchalal U, Rein AJ. Prevention of complete
intrauterine treatment of fetal supraventricular tachycar- heart block in children of mothers with anti-SSA/Ro and anti-
dia. Ultrasound Obstet Gynecol. 2002; 19:158-64. Epub SSB/La autoantibodies: detection and treatment of first-degree
2002/03/06. atrioventricular block. Curr Opin Rheumatol. 2009; 21:478-82.
178. Ebenroth ES, Cordes TM, Darragh RK. Second-line treatment Epub 2009/07/09.
of fetal supraventricular tachycardia using flecainide acetate. 193. Hutter D, Silverman ED, Jaeggi ET. The benefits of
Pediatr Cardiol. 2001; 22:483-7. Epub 2002/03/15. transplacental treatment of isolated congenital complete
179. Hahurij ND, Blom NA, Lopriore E, et al. Perinatal management heart block associated with maternal anti-Ro/SSA
and long-term cardiac outcome in fetal arrhythmia. Early Hum antibodies: a review. Scand J Immunol. 2010; 72:235-41.
Dev. 2011; 87:83-7. Epub 2010/11/27. Epub 2010/08/11.
180. Lopriore E, Aziz MI, Nagel HT, et al. Long-term 194. Friedman DM, Kim MY, Copel JA, et al. Prospective
neurodevelopmental outcome after fetal arrhythmia. Am J evaluation of fetuses with autoimmune-associated congenital
Obstet Gynecol. 2009; 201:46 e1-5. Epub 2009/04/07. heart block followed in the PR Interval and Dexamethasone
181. Schleich JM, Bernard Du Haut Cilly F, Laurent MC, et al. Evaluation (PRIDE) Study. Am J Cardiol. 2009; 103:1102-6.
Early prenatal management of a fetal ventricular tachycardia Epub 2009/04/14.
treated in utero by amiodarone with long term follow-up. 195. Jaeggi ET, Silverman ED, Laskin C, et al. Prolongation of the
Prenat Diagn. 2000; 20:449-52. Epub 2000/06/22. atrioventricular conduction in fetuses exposed to maternal anti-
182. Eliasson H, Wahren-Herlenius M, Sonesson SE. Mechanisms Ro/SSA and anti-La/SSB antibodies did not predict progressive
in fetal bradyarrhythmia: 65 cases in a single center analyzed heart block. A prospective observational study on the effects of
by Doppler flow echocardiographic techniques. Ultrasound maternal antibodies on 165 fetuses. J Am Coll Cardiol. 2011;
Obstet Gynecol. 2011; 37:172-8. Epub 2011/01/26. 57:1487-92. Epub 2011/03/26.
183. Horigome H, Nagashima M, Sumitomo N, et al. Clinical char- 196. Cuneo BF, Lee M, Roberson D, et al. A management strategy for
acteristics and genetic background of congenital long-QT fetal immune-mediated atrioventricular block. The journal of
82
syndrome diagnosed in fetal, neonatal, and infantile life: a maternal-fetal and neonatal medicine: the official journal of the
European Association of Perinatal Medicine, the Federation of
Asia and Oceania Perinatal Societies, the International Society
200. Pisoni CN, Brucato A, Ruffatti A, et al. Failure of intravenous
immunoglobulin to prevent congenital heart block: Findings
4
of Perinatal Obstet. 2010; 23:1400-5. Epub 2010/04/14. of a multicenter, prospective, observational study. Arthritis
FEtal Cardiology
197. Jaeggi ET, Nii M. Fetal brady- and tachyarrhythmias: new Rheum. 2010; 62:1147-52. Epub 2010/02/05.
and accepted diagnostic and treatment methods. Seminars 201. Ostensen M. Intravenous immunoglobulin does not prevent
in fetal & neonatal medicine. 2005; 10:504-14. Epub recurrence of congenital heart block in children of SSA/Ro-
2005/10/11. positive mothers. Arthritis Rheum. 2010; 62:911-4. Epub
198. Breur JM, Kapusta L, Stoutenbeek P, et al. Isolated congenital 2010/02/05.
atrioventricular block diagnosed in utero: natural history and 202. Friedman DM, Llanos C, Izmirly PM, et al. Evaluation of
outcome. The journal of maternal-fetal and neonatal medicine: fetuses in a study of intravenous immunoglobulin as preventive
the official journal of the European Association of Perinatal therapy for congenital heart block: Results of a multicenter,
Medicine, the Federation of Asia and Oceania Perinatal prospective, open-label clinical trial. Arthritis Rheum. 2010;
Societies, the International Society of Perinatal Obstet. 2008; 62:1138-46. Epub 2010/04/15.
21:469-76. Epub 2008/06/24. 203. Jaeggi ET, Fouron JC, Silverman ED, et al. Transplacental
199. Miyoshi T, Maeno Y, Sago H, et al. Evaluation of Transplacental fetal treatment improves the outcome of prenatally diagnosed
Treatment for Fetal Congenital Bradyarrhythmia. Circulation complete atrioventricular block without structural heart
Journal. 2012; 76:469-76. disease. Circulation. 2004; 110:1542-8. Epub 2004/09/09.
83
http://vip.persianss.ir
C hapter
http://vip.persianss.ir
1 Table 1
Regulators of ductal patency
Embryo to the Neonate
C
Figures 1A to C: The diagrammatic representation of duct-dependent circulations: A. Pulmonary atresia/ventricular septal defect; B. Hypoplastic
left heart syndrome; C. Transposition of great vessels. Ao = Aorta; LA = Left atrium; LV = Left ventricle; PA = Pulmonary artery; RA = Right
atrium; RV = Right ventricle.
Table 2
Classification of the CHDs with duct dependent circulation
Lesions which will depend on flow Lesions which will depend on the flow Lesions where the systemic and
via the ductus arteriosus to maintain via the ductus arteriosus to maintain pulmonary circulations are separated so
pulmonary circulation (Figure 1A) systemic circulation (Figure 1B) that mixing site is needed (Figure 1C)
Pulmonary atresia with or without Critical aortic stenosis Transposition of the great arteries.
ventricular septal defect (VSD)
Critical pulmonary stenosis Coarctation of the aorta
Tricuspid atresia Interruption of aortic arch
Tetralogy of Fallot (severe form) Hypoplastic left heart syndrome
Few selected cases of Ebstein’s anomaly
of the tricuspid valve
perfusion pressure for the whole body. Echocardiographic reflected by the heightened blood pressure in the upper limb
evaluation shows characteristic reverse filling of the arch and and the head. This differential response of blood pressure is
ascending aorta. primarily due to the renal response to hypoperfusion. The
In interrupted aortic arch and severe coarctation of aorta, opening of the duct in such situations would provide perfusion
the perfusion is less in the lower part of the body and it is volume and pressure for the lower extremities. Furthermore, 87
http://vip.persianss.ir
1 hypoplastic left heart syndrome (HLHS), leads to complete
intracardiac mixing of pulmonary and systemic venous blood.
The pulmonary artery is the single outlet for the total cardiac
Embryo to the Neonate
with the time of ductal constriction or closure (Table 3). These to the morbidity and mortality. Hence a detailed examination
babies often present in the first few days of life with incremental and parental counseling is required.
cyanosis. The neonatal cyanosis becomes more conspicuous
due to their higher hemoglobin levels. The central cyanosis Management
is dependent on absolute concentration of deoxygenated Hb
and is more than 3 grams/L in arterial blood and more than 5
Assessment
grams/L in capillary blood. A polycythemic neonate with Hb
of >20 grams/L will have evident cyanosis at the saturation of The general condition of babies with DDCHD is so critical
85 percent. On the contrary a neonate with Hb of 8 grams/L that urgent resuscitation and stabilization becomes the
will show it only when saturations falls below 70 percent. Also primary goal. Nevertheless, once baby is stable one must try
babies with higher fetal Hb level will have late visible cyanosis. to confirm the diagnosis in the following steps:
Very sick babies usually have cyanotic spell or congestive heart 1. Confirmation of presence of central cyanosis: First of
failure and circulatory collapse without clinical cyanosis. An all, central cyanosis must be confirmed by monitoring
inaudible murmur must not be criteria for exclusion of CHD in saturation with pulse oximetry (PO) and subsequently with
these patients and some times, the deterioration of the clinical arterial blood gas analysis. A sample from the right radial
condition with disappearance of murmur is a pointer for an artery is preferable. Monitor pre- and postductal oxygen
urgent intervention. The patient may have additional clinical saturations. If there is a difference of saturation in upper
features. There is a probability of involvement of multiple and lower limb of more than 3 to 7 percent, the chances
organs like kidney, brain or skeletal system, which may add up of having ductal flow from the pulmonary artery to aorta 89
http://vip.persianss.ir
1 are high. In first few hours, differential saturation may be Without PO, discharge of apparently healthy infants with
fallacious due to high pulmonary artery pressure and patent unknown CHD was 5.5 times and 4.1 times more likely in
duct. cyanotic CHD and all serious CHD, respectively.
Embryo to the Neonate
Table 4
Interpretation of the hyperoxia test30–32
PaO2 (mm Hg) at FiO2 = 0.21 PaO2 (mm Hg) at FiO2 = 1.00
PaCO2 (mm Hg)
(% saturation) (% saturation)
Normal 70 (95) > 300 (100) 35
Pulmonary disease 50 (85) > 150 (100) 50
Neurologic disease 50 (85) > 150 (100) 50
Methemoglobinemia 70 (95) > 200 (100) 35
#Cardiac disease
*Parallel circulation < 40 (< 75) < 50 (< 85) 35
**Mixing with restricted PBF < 40 (< 75) < 50 (< 85) 35
***Mixing without restricted PBF 40–60 (75–93) < 150 (< 100) 35
PaO2 = Arterial partial pressure of oxygen; FiO2 = Fraction of inspired oxygen; PaCO2 = Arterial partial pressure of carbondioxide; PBF = Pulmonary blood flow
*D-Transposition of the great arteries with intact ventricular septum.
**Tricuspid atresia with pulmonary stenosis or atresia, pulmonary atresia or critical pulmonary stenosis with intact ventricular septum, tetralogy of Fallot,
or Ebstein anomaly.
***Truncus arteriosus; total anomalous pulmonary venous return; single ventricle, hypoplastic left heart syndrome.
#The ratio of fetal to adult hemoglobin varies from infant to infant and the proportion of each hemoglobin affects the oxygen saturation. Thus, if a baby has
mostly adult hemoglobin, central cyanosis (arterial saturation 75–85%) will be observed when the PaO2 falls below 50 mm Hg. In contrast, if the baby has
90 mostly fetal hemoglobin, central cyanosis may not be observed, until the PaO2 drops well below 40 mm Hg. Thus, infants with a high proportion of fetal
hemoglobin may have a serious reduction in oxygenation before cyanosis is clinically apparent.
shock or circulatory collapse, severe metabolic acidosis. f. The babies with transposition physiology are severely 5
Intubation in HLHS is done, if evidence of pulmonary hypoxemic and may have PO2 < 20 mm Hg, high PCO2
overcirculation are present like arterial saturation more in the absence of lung causes and severe metabolic
Table 6
Prostaglandin–doses, preparation, monitoring37
http://vip.persianss.ir
1 Table 7
Side effects of prostaglandins48–56
Embryo to the Neonate
for increasing PaCO2 is preferred over hypoventilation, Ebstein’s anomaly is optimally stabilized on prostaglandin to
which may lead to atelectasis. It has been demonstrated support pulmonary blood flow. As PVR falls, a trial of wean-
that the hypercapnic acidosis (HCA) increases oxygen ing from prostaglandin must be done and the clinical pattern
delivery by 44 percent. Furthermore, there is evidence that of response must be assessed. Usually surgical management
HCA is a lung protective strategy that preserves pulmonary strategies are based on tricuspid valve regurgitation and de-
mechanics, attenuates lung protein leakage, reduces gree of cyanosis. If cyanosis alone is the dominant symptom, a
pulmonary edema and improves oxygen delivery in an systemic to pulmonary artery shunt alone is performed.
animal model of lung injury. However, when poor right ventricular function in association
3. PVR can be increased by decreasing the concentration of with severe tricuspid regurgitation is present, right ventricular
inspired oxygen and by adding supplemental nitrogen gas exclusion by patching the tricuspid valve is the best option.
to attain a FiO2 of 17 to 19 percent. Additionally, PVR can This is one condition where actively pulmonary vasodila-
also be increased by maintaining the hematocrit greater tation is attempted, if weaning of PGE1 fails. Trial of nitric
than 40 percent, a state that optimizes oxygen-carrying oxide has been attempted in many centers. Sildenafil also was
capacity and increases the viscosity of the blood. tried successfully in few case reports.45
Newborn with Severe Ebstein Anomaly of Tricuspid Total Anomalous Pulmonary Venous Connection:
Valve: Issue of PGE1 Infusion41–45 Effect of Prostaglandins46–48
The Ebstein anomaly is not only a tricuspid valve disease, but Routinely, cyanotic CHDs with severe hypoxemia can be put
also disease of the right ventricle and right atrium, or right heart on prostaglandin infusion without any harm before sending
disease. Of all neonates with the diagnosis of Ebstein anomaly, them to a tertiary cardiac care center, when facility for
20 to 40 percent will die in a month. Like in HLHS, the pre- echocardiography is not available and exact diagnosis cannot
surgical and surgical management of critically ill neonates and be made. However, there are some concerns regarding its use
young infants with Ebstein anomaly remains challenging. The in total anomalous pulmonary venous connection (TAPVC)
problems which can influence the overall outcome are diminu- espcially the obstructed type. PGE1 could produce adverse
tive and dysfunctional right ventricle, severity of tricuspid re- effects by two mechanisms:
gurgitation, severity of right ventricular outflow obstruction, 1. By increasing the cyanosis and hypoxemia of systemic
size of pulmonary arteries, severity of pulmonary hypertension circulation: When the pulmonary arterial pressure is higher
92 and dysfunctional left ventricle. The symptomatic neonate with than that in the aorta, dilatation of the DA may result in
an increase in right-to-left shunt and would increase in the systemic circulation, a ductal stenting or high-risk modified 5
degree of cyanosis. Norwood procedure is expected. In transposition physiology,
2. By direct pulmonary vasodilatation leading to altered Qp : if baby fails to stabilize, a balloon atrial septostomy could be
Prostaglandins are great rescuers for babies with duct- INTERVENTION IN DUCT DEPENDENT congenital
dependent circulation. However, PGE1 infusion is not totally heart diseases: DUCTAL STENTING
safe. The problems are associated with gestational age and
type of lesions. Mc Elhinney et al followed-up 643 babies With growing interest in catheter interventions and persistent
with complex congenital anomaly and they found 3.3 percent high mortality related to shunt surgery, efforts were made to
incidence of necrotizing enterocolitis and it showed high explore the new possibilities to maintain the ductal patency.
correlation with prematurity and little higher PGE1 infusion Moreover, arterial duct stabilization with a high-flexibility
rate (> 0.5 mcg/kg/min).51 There is risk of apnoea requiring coronary stent is an effective alternative in high-risk surgical
ventilation particularly in premature, low-birth-weight (LBW) candidates or whenever short-term pulmonary blood flow
newborn.48–56 support is anticipated. It seems highly logical to try to keep
the duct open rather than going for a surgical alternative
Transport of a Baby with Duct-dependent with prosthetic material. We know prostaglandins are highly
Congenital Heart Disease38,57 effective at maintaining duct patency medically in the short
term. They become less reliable and have more side-effects if
Early diagnosis and optimization of blood biochemistry, given long-term. Ductal stenting at cardiac catheterization was
adequate oxygenation, if required ventilation and prostaglandin first described in the early 1990s.58 Even though technique of
infusion to maintain the adequate Qp : Qs ratio is important. stenting has not changed appreciably in the past 15 years, stent
In tetralogy of Fallot (TOF) physiology, usual goal in a case and balloon technology is becoming better. With the future
of duct-dependent pulmonary circulation is to do modified advancement and training, one can think of better outcome of
Blalock-Taussig shunt or ductal stenting. In duct-dependent this promising and life-saving procedure (Table 8).
Table 8
Recommendation for ductal stenting (a scientific statement from the American Heart Association)61
1. Recommendations for patent ductus arteriosus (PDA) stenting for the purpose of augmenting pulmonary blood flow
Class IIa It is reasonable to stent an anatomically suitable ductus arteriosus in an infant with cyanotic congenital heart
disease (CHD) who has >1 source of pulmonary blood flow (antegrade pulmonary blood flow or collateral blood
flow), but who requires additional pulmonary blood flow from the stented ductus for a relatively short period of
time (3–6 months) (Level of Evidence: B).
Class IIb It might be reasonable to stent an anatomically suitable PDA in an infant with cyanotic CHD whose sole
source of pulmonary blood flow is the ductus (Level of Evidence: C).
Class III Ductal stenting should not be performed in an infant with cyanotic CHD who has obvious proximal pulmonary
artery stenosis in the vicinity of the ductal insertion (Level of Evidence: C).
2. Recommendations for a hybrid approach to hypoplastic left heart syndrome (HLHS) and complex single ventricle
Class IIa It is reasonable to perform hybrid stage I palliation, consisting of right and left pulmonary artery banding,
PDA stent implantation and creation of an unrestrictive atrial communication, by combining transcatheter
and surgical techniques without cardiopulmonary bypass as an alternative to conventional surgery in
neonates with HLHS or complex single ventricle, in high-risk surgical candidates and as a bridge to heart
transplantation (Level of Evidence: B).
Class IIb Hybrid stage I palliation may not be indicated in a patient who has significant retrograde aortic arch
obstruction at the time of initial diagnosis that might be further compromised by placement of the PDA stent.
This decision should be a collaborative decision between the interventional cardiologist and a congenital 93
heart surgeon (Level of Evidence: C).
http://vip.persianss.ir
1 Advantages of Ductal Stenting and radial force. The stent characteristics like larger metallic
cross-sectional area, thicker struts, and smaller cell area give
1. Eliminating the need for neonatal palliative surgery. good scaffolding with limited tissue prolapse. However, these
Embryo to the Neonate
2. Reducing the number of operations required. properties reduce the flexibility and conformability of the
3. Optimizing the time of definitive surgical correction. stent, and are known to enhance in-stent restenosis rate in
coronary arteries. Balloon redilatation or additional stent can
Procedure59,60 be deployed to avoid residual stenosis. The radial force and
side-branch accessibility are no issue for a stent deployed in the
Ductal stenting is done in the catheterization laboratory under arterial duct. A thin but complete layer of endothelium forms
general anesthesia. Angiography is done to demonstrate the over the stent as early as 1 month. Neoendothelial proliferation
anatomy and to measure the length of the arterial duct. IV plays an important role in duct-dependent pulmonary blood
heparin (50 U per kg) must be given. Cefazolin 30 mg per kg flow. There could be gradual fall in oxygen saturation as the
is administered prior to stent implantation, followed by another duct becomes compromised by neoendothelium.
two doses at the interval of 8 hours. Prostaglandin infusion can Alwi and colleagues demonstrated that PDA stent
be stopped several hours before the procedure, so that duct can accelerates pre-existing stenosis of the pulmonary arteries,
have grip over stent. Prostaglandin inhibitors can be used in primarily in the LPA. They concluded that the stent metal
selected cases. grid provokes intense neointimal proliferation and fibrosis in
The antegrade approach through femoral vein or retrograde the ductal tissue encircling the pulmonary arteries.60 Because
approach through femoral artery can be used. For antegrade the pulmonary artery implants at the LPA origin, the higher
approach in a case of pulmonary atresia, perforation of incidence of stenosis in this branch can be explained by the
pulmonary valve would be required. concomitant effect of the pulmonary coarctation and the
The procedure for stent implantation has to be individuali neointimal hyperplasia. Fortunately there are attempts to evolve
zed, since origin and morphology of the duct varies in novel technologies. The innovative methods like rapamycin-
different CHDs. In patients with pulmonary atresia with coated drug eluting stents have been experimented in newborn
intact interventricular septum, the approach can be either pigs successfully.
antegradely through the pulmonary artery after the perforation The palliation obtained from ductal stenting, is less reliable
of atretic valve or it can be done retrogradely. In patients with and of shorter duration than that expected from a surgical
pulmonary atresia with VSD also, the approach has to be either aortopulmonary shunt. In HLHS, a more complex hybrid
antegrade or retrograde. For better support during delivery of approach (selective pulmonary artery bandings without
the stent, a 4F long sheath (Mullin) can be used. After entering cardiopulmonary bypass followed by percutaneous PDA stent
pulmonary artery, by using an end-hole catheter, a 0.014 implantation and balloon dilation of the atrial septum) was done
coronary wire is introduced via arterial route to cross the DA. by Akinturk et al in 2002 with little better results.61 However,
Over this wire, the delivery system with the coronary stent duct stenting in HLHS as a part of combined procedure, is still
may be advanced into the duct. After confirming the correct an unpredictable and technically demanding procedure and not
position of the stent across the duct, the balloon is inflated in recommended as Class I indication.
order to deploy the stent. Post stenting, anticoagulation and
prevention and management of the restenosis are important.
Bioengineering in Duct Patency
Acetylsalicylic acid, 1 to 3 mg/kg/day, is started for as long as
stent patency is required. Stent restenosis can be treated with Transfection is the delivery of DNA, RNA, proteins, and
ballooning and restenting. macromolecules into the eukaryotic cells. Based on the belief
that a protein called fibronectin, the concentration of which
increases in the advanced stage of gestation, is responsible
Modifiers for Success of the Procedure59–61
for closure of the duct, the gene for a fibronectin 'decoy'
The success of procedure depends on the type and length of was introduced directly in utero in the ductal tissue to keep
PDA, type of stents and experience of operator. A stented duct is ductal patency in animal experiments. Percutaneous postnatal
more comparable with a central shunt, which has no restriction transfection of gene for PG in ductal tissue also ensured
at the aortic end. Usual size of surgical shunt in neonate is 3 prolonged patency of duct. These and several other projects
to 4 mm. The final lumen within the stent, will depend on the are underway to get the safest technique to keep duct open.2
stent diameter at the time of implantation. The diameter of
lumen decreases by contraction of the vessel wall leading to Conclusion
tissue prolapse through the stent struts. This process starts after
few hours of stent placement. Further decrease in size of lumen Duct-dependent congenital heart diseases are life-threatening
is secondary to endothelial hyperplasia. The stent’s design and cardiac emergencies and need to be recognized as early as
94 material determines the cross-sectional area, strut thickness possible. Medical intervention with prostaglandin infusion
provides time for referral and planned definitive repair. Many 15. Elliot RB, Starling MB, Neutze JM. Medical manipulation of
patent ductus arteriosus. Lancet. 1975; 1:140-2.
5
babies need to be supported with inotropes and ventilation,
which needs to be customized according to the type of 16. Heymann MA, Rudolph AM, Silverman NH. Closure of
http://vip.persianss.ir
1 35. Wernovsky G, Ades AM, Spray TL. Management of congenital
heart diseases in low birth weight infants; In Avery’s Diseases
49. McElhinney D, Hedrick H, Bush D, et al. Necrotizing
enterocolitis in neonates with congenital heart disease: risk
of the Newborn, 8th edition. Taeusch HW, Ballard RA, Glea- factors and outcomes. Pediatrics. 2000; 106:1080-87.
Embryo to the Neonate
son CA (Eds), Elsevier 2004; 888-895. 50. Lewis AB, Freed MD, Heymann RA, et al. Side effects of
36. Shan F, Shekerdemian L, Millar J, et al. Early management of therapy with prostaglandin E1 in infants with critical congenital
infants with hypoplastic left heart syndrome. Hhs. 2008. doc; heart disease. Circulation. 1981; 64:893-98.
http://www.rch.org.au/emplibrary/picu/HLHS.pdf. 51. Sone K, Tashiro M, et al. Long-term low dose prostaglandin
37. Day RW, Barton AJ, Pysher TJ. Pulmonary vascular resistance E1 administration. J Pediatr. 1980; 97:866-67.
of children treated with nitrogen during early infancy. Ann 52. Kaufman MB, El-Chaar GM. Bone and tissue changes following
Thorac Surg. 1998; 65:1400-4. prostaglandin therapy in neonates. Ann Pharmacother. 1996;
38. Dessardo S, Ahe V. Preoperative management of hypoplastic 30:269-74,277.
left heart syndrome. SIGNA VITAE. 2009; 4:12-15. 53. Peled N, Dagan O, Babyn P, et al. Gastric-outlet obstruction
39. Kinouchi K, Okawa M, Fukumitsu K. Perioperative manage- induced by prostaglandin therapy in neonates. New Engl J
ment of two neonates with severe Ebstein’s anomaly with pul- Med. 1992; 327:505-10.
monary atresia. Masui. 2000; 49:1274-7. 54. Heffelfinger S, Hawkins EP, Nihill M, et al. Pulmonary vascular
40. Jaquiss RD, Imamura M. Management of Ebstein’s anomaly changes associated with prolonged prostaglandin E1 treatment.
and pure tricuspid insufficiency in the neonate. Semin Thorac Pediatr Pathol. 1987; 7:165-73.
Cardiovasc Surg. 2007; 19:258-63. 55. Transfer of Babies with Duct Dependent Congenital Heart
41. Bove EL, Hirsch JC, Ohye RG, et al. How I Manage Neonatal Disease. Neonatal transfer service. NHS. http://www.neonatal.
Ebstein’s Anomaly. Semin Thorac Cardiovasc Surg Pediatr org.uk/documents/1457.pdf.
Card Surg Ann. 2009; 12:63-65. http://cardiopedhnn. 56. Rosenthal E, Qureshi SA, Kakadekar AP, et al. Comparison
comfypage.com/site/UserFiles/Ebstein-Neonatal-Sx.pdf. of balloon dilation and stent implantation to maintain patency
42. Pham P, Hoyer A, Shaughnessy R. A Novel Approach Incorpo- of the neonatal arterial duct in lambs. Am J Cardiol. 1993;
rating Sildenafil in the Management of Symptomatic Neonates 71:1373-76.
with Ebstein’s Anomaly. Pediatric Cardiology. 2006; 27:614- 57. Gewillig M, Benson LN. Stenting the Neonatal Arterial Duct
17. in Duct-Dependent Pulmonary Circulation: New Techniques,
43. Aggarwal S, Chintala K, Humes RA. Sildenafil use in a Better Results. J Am Coll Cardiol. 2004; 43:107-12.
symptomatic neonate with severe Ebstein’s anomaly of the 58. Djer MM, Alwi M. Stent implantation into ductus arteriosus:
tricuspid valve. Am J Perinatol. 2008; 25:125-28. a new alternative of palliative treatment of duct-dependent
44. Chang AC, Burke RP. Anomalous pulmonary venous connec- pulmonary circulation. Paediatrica Indonesiana. 2004;
tion. In Pediatric cardiac intensive care, Chang AC, Hanlay 44(1-2).
FL, Wernovsky G, Wessel DL (Eds). Williams and Wilkins, 59. Boucek MM, Mashburn C, Kunz E, Chan KC. Ductal anatomy:
Toronto. 1998; 223-28. a determinant of successful stenting in hypoplastic left heart
45. Bullaboy CA, Johnson DH, Ajar H. Total anomalous syndrome. Pediatr Cardiol. 2005; 26:200-5.
pulmonary venous connection to portal system: A new role for 60. Alwi M. Initial results and midterm follow-up of stent
prostaglandin E1. Pediatric Cardiology. 1984; 5:115-16. implantation of patent ductus arteriosus in duct dependent
46. Product information. Prostin VR Pediatric. The Up John pulmonary circulation. J Am Coll Cardiol. 2004; 44:438-45.
Company; Kalamazoo, MI. January 1995. 61. Akinturk H, Michel-Behnke I, Valeske K, et al. Hybrid
47. Host A, Halken S, Kamper J, et al. Prostaglandin E1 treatment transcatheter-surgical palliation: basis for univentricular or
in ductus dependent congenital cardiac malformations: a biventricular repair: the Giessen experience Pediatr Cardiol
review of the treatment of 34 neonates. Dan Med Bull. 1988; 2007; 28:79-87
35:81-84. 62. Feltes TF, Bacha E, Beekman RH, et al. Indications for Cardiac
48. Kramer HH, Sommer M, Rammos S, et al. Evaluation of Catheterization and Intervention in Pediatric Cardiac Disease:
low dose prostaglandin E1 treatment for ductus dependent A Scientific Statement From the American Heart Association
congenital heart disease. Eur J Pediatr. 1995; 154:700-07. Circulation. 2011; 123:2607-52.
96
C hapter
Genetics in
6 Congenital Heart Diseases
The first reference in history to the presence of congenital techniques.3,4 Therefore, the number of adults with a CHD
heart disease (CHD) comes from a Babylonian tablet, which is on the rise. Once these patients enter the reproductive age
dates back to around 4,000 BC. The description mentions; group, knowledge of heritability of such defects is essential.
“When a woman gives birth to an infant that has the heart Isolated congenital heart defects are most frequently sporadic.
open and has no skin, the country will suffer from calamities”, Despite the sporadic nature, a genetic component is still very
which might refer to ectopia cordis (Figure 1). likely to contribute to the occurrence of these defects and there
Leonardo da Vinci, was the first to describe a congenital is a higher recurrence risk among siblings and offspring of
heart defect in humans in his Quaderni de Anatomia.1 patients with CHD.5,6 CHD, being a complex trait, is thought
Congenital heart disease is the leading cause of infant to be multifactorial.7 Even though, extensive knowledge of the
morbidity in the western world, but only in the past 10 years its genetic control of cardiogenesis in animals is available, this
etiology has been understood. Recent studies have uncovered has not been translated into an equivalent amount of clinical
the genetic basis for some common forms of the disease and knowledge of the genetic determinants of CHD in humans.
provide new insight into how the heart develops and how
dysregulation of heart development leads to disease.2 In this EmbryoloGy
day and age, about 85 to 95 percent of the children with CHD
survive into adulthood due to better surgical and non-surgical Congenital heart diseases arise from abnormal heart develop-
ment during embryogenesis, so understanding how the heart
forms normally is important. The heart is the first organ to form
in an embryo and must function to support the rapidly growing
embryo before it has the opportunity to shape itself into the
four chambered organ (Figures 2A and B). The combination
of complex morphogenetic events necessary for cardiogenesis
and the superimposed hemodynamic influences may contribute
to exquisite sensitivity of the heart to perturbation. The fraction
of congenital heart malformations, that are hemodynamically
compatible with the intrauterine circulation form the spectrum
of CHD, that is observed clinically.8
The earliest cardiac progenitors arise from lateral plate
mesoderm, controlled by a cascade of interacting transcription
factors. Discovery of a ‘second’ heart field (SHF) led to
rethinking of the origin and patterning of the embryonic heart.
The SHF is medial and dorsal to the early differentiating
cardiomyocytes that comprise the ‘cardiac crescent’, and
gives rise to a large portion of the heart, including the outflow
tract, right ventricle and most of the atria. The SHF is further
subdivided into a number of lineage pools, which contribute
either to anterior structures (such as the outflow tract) or
Figure 1: Ectopia cordis posterior components (such as the atria).9
http://vip.persianss.ir
1
Embryo to thE NEoNatE
b
Figures 2a and b: Heart development. [Reprinted with permission from Macmillan Publishers Ltd. Nature, Bruneau, 2008, P 946] (A = Artery;
AO = Aorta; AS = Atrial septation; CC = Cardiac cushions; FHF = First heart field; LA = Left atria; LV = Left ventricle; OT = Outflow tract; PA =
Pulmonary artery; RA = Right atria; RV = Right ventricle; SHF = Second heart field; SV = Sinus venous; V = Ventricle, VS = Ventricular septum)
98
Human genetic studies have identified numerous genes allele have similar cardiac abnormalities to those seen in 6
that are responsible for inherited and sporadic congenital heart Holt–Oram syndrome, with septal defects and atrioventricular
diseases. Most of these genes encode transcription factors (AV) conduction block.12,14 Mouse TBX20 is expressed in the
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b
c D
Figures 3a to D: Baby with Down syndrome and karyotype of Trisomy 21
101
Figure 5: 4D fetal image showing preauricular tag and retrognathia Figure 6: Karyotype: Tetrasomy 22q
http://vip.persianss.ir
1 be at least 1 in 4,000–6,000 livebirths, but this might be an
underestimation as many cases with mild features may remain
undiagnosed.21–23
Embryo to thE NEoNatE
102 a b
Figures 9a and b: DiGeorge syndrome. A. Mother and B. Child
6
development is often delayed and impaired with almost Wolf–Hirschhorn Syndrome (OMIM: 194190)
always hypernasal voice. Additionally, affected children are
more likely to have attention deficit hyperactivity disorder Wolf–Hirschhorn syndrome is due to deletion of the terminal
(ADHD) and developmental disorders such as autism that segment of chromosome 4p (Figures 12A and B). There is
affect communication and social interaction. Hypocalcemia an increased incidence of cleft lip, palate, seizures and heart
may present with seizure activity, but responds promptly to disease (30%).
replacement therapy and becomes less apparent with age. The
immune deficit also resolves with time and is often less evident Alagille Syndrome (OMIM: 118450)
than in the original case. Later in life, they are at an increased
risk of developing mental illnesses such as schizophrenia, Alagille syndrome is characterized by prominent forehead,
depression, anxiety and bipolar disorder. A variety of cardiac deep set eyes, thin nose, butterfly vertebrae, arcus juvenilis
malformations are seen particularly affecting the outflow with pulmonary artery stenosis (Figure 13). It is caused by
tract. These include TOF, interrupted aortic arch (IAA), VSD,
trucus asteriosus (TA), right aortic arch and aberrant right
subclavian artery.
This disorder has an autosomal dominant inheritance
pattern. Familial cases of DGS have been described in 6 to 28
percent, but usually DGS occurs sporadicaly and results from
a de novo deletion, which occurs most often as a random event
during the formation of reproductive cells (eggs or sperm) or
in early fetal development 22q11.2 microdeletion.24 Although
the penetrance of a 22q11 deletion is nearly 100 percent, the
severity of the disorders is variable.
http://vip.persianss.ir
1
Embryo to thE NEoNatE
a b
Figures 12a and b: 4p deletion. A. Karyotype report and B. FISH report
Figure 13: Pulmonary artery stenosis in Alagille syndrome Holt–Oram Syndrome (OMIM: 142900)
Holt–Oram syndrome was first describe by Holt and Oram
in 1960. It is characterized by upper limb defect, narrow
shoulders and cardiac anomaly (Figures 15A and B). Cardiac
anomaly in majority includes secundum ASD with occasional
reports of VSD, AVSD and TA. It is caused by mutation of
TBX5 gene, which is linked to chromosome 12q24.1.
Figure 16: Baby with Ellis-van Creveld and polydactyly of hands Figure 18: Adult showing short upper lip bound
by frenula to alveolar ridge
metabolic Disorder
http://vip.persianss.ir
1 There is accumulation of glycogen in certain organs and NKX2–5 (omim: 600584) NK2 Homeobox 5/CSX
tissues. It is manifested as hypotonia, generalized muscle
weakness, feeding difficulties, failure to thrive, cardiomegaly Homeobox genes have been found to play a crucial
Embryo to thE NEoNatE
and hypertrophic cardiomyopathy. role in regulating tissue specific gene expression. The
cardiac homeobox protein NKX2-5 is essential in cardiac
Zellweger Syndrome (OMIM: 214100) development and mutations in CSX (cardiac-specific
homeobox which encodes NKX2-5) cause various congenital
Zellweger syndrome is characterized by hypotonia, high heart malformations. The earliest molecule marker of the
forehead, flat facies, hepatomegaly and CHDs like PDA cardiac lineage is NKX2-5 in vertebrates. It is one of the
and septal defect. It is caused by defects in number of PEX members of NK2 family of homeobox genes and a homolog
genes. of the Drosophila tinman.25 It has highly conserved regions
of DNA binding, protein-protein interactions, nuclear
Smith–Lemli–Opitz Syndrome (OMIM: 270400) translocation, and regulation of other transcription factors.
Their homeodomains have a tyrosine at position 54,
Smith–Lemli–Opitz syndrome is characterized by severe making it the most unambiguous feature of this class and
learning disability, failure to thrive, cleft palate, bitemporal is a useful classification tool.26 Mutations in this gene have
narrowing, anteverted nares and syndactyly. Fifty percent been reported to cause ASD, VSD with atrial ventricular
will have CHDs like AVSD or ASD. It is due to severe block, TOF and tricuspid valve abnormalities. Mutations in
defect in cholesterol biosynthesis resulting in deficiency this gene can also cause congenital hypothyroidism, non-
of 7-dehydrocholestrol reductase (DHCR7) gene, which is goitrous type 5, a non-autoimmune condition.27
mapped to chromosome 11q12–13. Turbay and group28 mapped the CSX gene to chromosome
5q35, close to the junction with band 5q34.
GEnES ASSoCiAtED witH CHD Pauli and group29 described a distal 5q deletion, with
karyotype del(5)(q35.1q35.3), in a 7½-year-old girl who, in
Most of the isolated congenital heart defects do not show addition to ASD and PDA, had ventricular myocardial non-
a typical Mendelian inheritance pattern, but as mentioned compaction. Fluorescent in situ hybridization (FISH) analysis
earlier a genetic component is very likely to contribute showed that this deletion included the locus for CSX. Thus,
(Table 1). they suggested that some instances of ventricular myocardial
table 1
Genes causing different types of CHDs with their chromosomal region in humans18
IRX4 5p15.3 SV
Elastin 7q11 AS
Fibrillin 15q21 AA
AA = Ascending aorta; AS = Aortic stenosis; ASD = Atrial septal defect; AV = Atrioventricular; AVSD = Atrioventricular septal defect;
106 HLHS = Hypoplastic left heart syndrome; PDA = Patent ductus arteriosus; TOF = Tetralogy of Fallot; VSD = Ventricular septal defect
non-compaction may be caused by haploinsufficiency of mice, germline ablation of the gene encoding GATA4 results 6
CSX. They reviewed four other cases with deletions in the in abnormal ventral folding of the embryo, failure to form a
same region of 5q and pointed out that two of them had atrial single ventral tube and lethality. Besides heart development,
http://vip.persianss.ir
1 common features reported with partial monosomy of 8p include hypoparathyroidism and three with DGS) and one patient
growth and mental retardation, impulsive and aggressive with VCFS and a large interstitial deletion. FISH analysis
behaviour, congenital cardiac defects, diaphragmatic hernia demonstrated that these patients had overlapping deletions at
Embryo to thE NEoNatE
and in males, genital abnormalities. Devriendt and group43 the 10p13/10p14 boundary. They concluded that the results
have performed genotype-phenotype correlations in nine strongly support the hypothesis that haploinsufficiency of a
unrelated patients with a de novo del 8p. In five patients, a gene or genes within 10p (DGSII locus) can cause the DGS/
uniform interstitial deletion of approximately 6 Mb in 8p23.1 VCFS spectrum of malformations.
was detected. One patient carried a large terminal deletion Schuffenhauer and group52 performed FISH and
encompassing this commonly deleted region. All these polymerase chain reaction (PCR) analyses in 12 patients with
patients have a similar phenotype, with a CHD, microcephaly, 10p deletions, nine of them with features of DGS and in a
mild developmental delay, intrauterine growth retardation, familial translocation 10p;14q associated with midline defects.
and a characteristic behavioral phenotype. Features that have The critical DGS2 region was defined by two DGS patients
been recognized more recently are a characteristic behavioral and mapped within a 1-cM interval including D10S547 and
phenotype, hypospadias, and seizures.44 The del(8p) D10S585. The other seven DGS patients were hemizygous
phenotype often is relatively mild, without associated facial for both loci. The breakpoint of the reciprocal translocation
dysmorphism or other major internal malformations.45-47 10p;14q mapped at a distance of at least 12 cM distal to
They defined an 8p heart defect—critical region spanning a the critical DGS2 region. Interstitial and terminal deletions
10-cM segment defined distally by D8S1706 and proximally described in these patients were in the range of 10 to 50 cM
by D8S1759 and they suggested the transcription factor and enabled the tentative mapping of loci for ptosis and hearing
GATA4 as a candidate gene. loss, features that are not part of the DGS clinical spectrum.
Giglio and group48 narrowed this region by studying Lichtner and group53 reported a new case with the high
12 del(8p) patients, including 6 new cases, 7 of whom had dynamic range (HDR) phenotype: hypoparathyroidism,
CHDs. Patients with 8p deletions distal to D8S1706, at deafness and renal dysplasia. They were found to have partial
approximately 10 cM from the 8p telomere, did not have monosomy for 10p due to terminal deletions with breakpoints
CHD, whereas patients with a deletion that included the more between D10S585 and D10S1720. By comparison with data
proximal region suffered from the spectrum of heart defects previously published on patients with DGS/VCFS associated
reported in patients with 8p distal deletions. The 5-cM critical with 10p monosomy, they concluded that this is a contiguous
region is flanked distally by D8S1706 and WI-8327, both at gene syndrome. Hemizygosity for a proximal region can cause
approximately 10 cM and proximally by D8S1825, at 15 cM. cardiac defects and T-cell deficiency; hemizygosity for a more
distal region can cause hypoparathyroidism, sensorineural
Second DiGeorge Syndrome locus (DGSii) deafness and renal dysplasia.
(omim: 601362) Berend and group54 tested 412 patients, 54 were found
to be deleted for the DGSI locus on chromosome 22 (13%),
The DiGeorge syndrome and velocardiofacial syndrome may and a single patient was found deleted for the DGSII locus on
present many clinical problems, including cardiac defects, chromosome 10 (0.24%). The patient with the 10p deletion
hypoparathyroidism, T-cell immunodeficiency and facial had facial features consistent with VCFS, plus sensorineural
dysmorphism. They are frequently associated with deletions hearing loss, and renal anomalies. Cytogenetic analysis
within 22q11.2, but a number of cases have no detectable showed a large deletion of 10p [46, XX,del(10)(p12.2p14)]
molecular defect of this region. Bourrouillou and group49 and FISH using a 10p telomere region-specific probe
described a case of monosomy 10p with microcephaly, confirmed the interstitial nature of the deletion.
antimongoloid slant of the palpebral fissures, low-set ears, Lichtner and group55 constructed a deletion map of partial
prominent anthelix, congenital heart disease and abnormalities monosomy 10p patients and narrowed the critical region
of the limbs. Schuffenhauer and group50 described a DGCRII to about 300 kb. The genomic draft sequence of this
20-month-old girl with DGS and a monosomy 10p13→pter region contains only one known gene, BRUNOL3 ( NAPOR,
and a trisomy 10q26→qter due to a meiotic recombination of CUGBP2, ETR3). In situ hybridization of human embryos and
a maternal inversion (10)(p13q26). The proposita's phenotype fetuses revealed as well as in other tissues a strong expression
demonstrates typical features of the del(10p) syndrome, of BRUNOL3 in thymus during different developmental
which include mental retardation, abnormally shaped skull, stages. BRUNOL3 appears to be an important factor for
hypertelorism, low nasal bridge, micrognathia, dysmorphic thymus development and is therefore a candidate gene for the
low set ears, short neck, foot abnormalities and cardiac defect. thymus hypoplasia or aplasia seen in partial monosomy 10p
Daw and group51 stated that a number of single case reports patients. Many patients with the mild end of the DGS/VCFS
with deletions of 10p suggested genetic heterogeneity of spectrum have been referred to the cytogenetics laboratory
DGS. They compared the regions of hemizygosity in four by the physicians for FISH for the deletion on 22q11.2 and
108 patients with terminal deletions of 10p (one patient with high resolution G-banded analysis has been requested for only
those patients with a more severe presentation, although the Greenberg and group62 observed partial monosomy due 6
most effective method for detecting all possible cytogenetic to an unbalanced 4;22 translocation in a two-month-old male
abnormalities would be to perform a complete chromosome with type 1 TA and features of DGS. The asymptomatic
http://vip.persianss.ir
1 systematic prenatal diagnosis of aneuploïdies, the addition Flow chart 2: Genes on 22q11 and 22q13 regions
of 22q11.2 deletion studies to standard cytogenetics
should be considered. Similarly, isolated increased nuchal
Embryo to thE NEoNatE
PrEnAtAl DiAGnoSiS
In the literature, transabdominal amniocentesis in the third
trimester has been reported by Prochownick, Von Schatz
and Lambl in 1877 and Schatz in the 1890. The first use of
amniotic fluid examination in the diagnosis of genetic disease
was reported by Fuchs and Riis in 1956, in their seminal
article in ‘Nature’. They determined fetal sex from cells
found in amniotic fluid, basing on the presence or absence
of the Barr body.91 The determination of fetal sex led to the
prenatal management of patients with haemophilia A in 1960
110 and Duchenne muscular dystrophy in 1964. Steele and Breg
very importantly demonstrated in their seminal paper in the and microglossia. It is therefore imperative that chorionic 6
Lancet in 1966 that cultured, amniotic fluid cells were suitable villus sampling is performed only after 11 weeks and before
for karyotyping.92 The year 1966 is an important milestone 15 weeks by appropriately trained operators.95
http://vip.persianss.ir
1 than the cells, it contains. This causes the cells to absorb the best possible amendment to the disorder in an affected
water through their membranes and swell (but not burst). member.101
The swollen cells allow the chromosomes to readily separate, During genetic counseling, emphasis is placed on respecting
Embryo to thE NEoNatE
making them easier to count. During the ‘trisomy period’: the experiences of the patients and/or family and on patient
Cytogeneticists discovered patients with an additional autonomy in decision making so that an informed decision is
copy of a small chromosome, e.g. Trisomy 21 (Down made. A psychotherapeutic component of genetic counselling
syndrome), Trisomy 13 (Patau syndrome) and Trisomy 18 is desirable as the occurrence of a genetic condition can have
(Edward syndrome). Numerical abnormalities involving a family-wide impact and the clinician or genetic counselor
sex chromosomes (the X and Y chromosomes) were also should provide acceptance and empathy, but should never
described for the first time and such as Turner syndrome ‘play God’. Genetic counselling should be non-directive,
and Klinefelter syndrome. Further advances in technology presenting all information to the patient in a non-judgmental
led to banding techniques (hence the ‘banding era’), which and neutral approach. This will enable the patient to make a
brought out horizontal bands of differential staining intensity. decision best suited to their situation.
The most recent developments in cytogenetics have led to In cases where congenital heart defects are picked up
the ‘molecular era’. Advances in the use of DNA probes prenatally, it is important to address the immediate concerns
have allowed cytogeneticists to hybridize these probes to of the couple. The most important issues to discuss during a
chromosomes and determine if a specific DNA sequence prenatal visit are accuracy of prenatal testing, risks of prenatal
is present on the target chromosome. This has been useful testing, recurrence risks for the couple and family and most
in detecting abnormalities beyond the resolution level of importantly, what to expect, when undergoing prenatal
studying banded chromosomes at the microscope, and also in diagnosis. It is easy to assume what needs to be addressed
determining the location of specific genes on chromosomes. during the session, however, it is important to identify
Recent advances in cytogenetic techniques made a valuable the expectations and issues, the patient is facing. In our
contribution toward the practice of modern medicine.97,98 experience, the least important issues during the initial genetic
The FISH is a molecular cytogenetics technique that allows counselling session with the couple are pregnancy termination
identification and detection of the gene of interest within its options, discussions as to whether the couple should have
natural environment of chromosomes, cells or tissues. The another child and other reproductive options. It is optimum if
basic principle involved in this technique is natural affinity of these issues are addressed during the follow-up session.
base pairing of nucleotide sequences with the complementary Testing in the form of prenatal diagnosis should be
sequences. Pardue and Gall99 reported the hybridization of offered for an etiological diagnosis and its implication in the
radioactive DNA probes for repetitive sequences to mouse management and prognosis of the condition. In cases where
and drosophila chromosomes. In 1981 Harper and Saundres the cardiac defect is not amenable to surgical correction, the
reported an improved technique for in situ hybridization investigations will help in providing information in the form
allowing detection of unique DNA sequence along human of recurrence risks for future pregnancies. In developing
metaphase chromosome spread.100 countries, where affordability of health care is an issue for
The FISH allows rapid analysis of chromosome copy number majority of the population, the genetic counselor should be
in interphase cells of amniotic fluid, chorionic villi, cord blood supportive of the couple’s decision to undergo termination
and peripheral blood samples. It has been extensively applied of pregnancy, where the long-term prognosis, in absence of
in cancer cytogenetics to confirm various translocations. It is appropriate medical intervention, is poor.
also used for detection of microdeletion (less than 5 million
base pairs size) syndromes like DiGeorge syndrome, Prader– SummAry
Willi Syndrome, etc. Various types of FISH probes such as
centromeric, α-satellite, locus specific, telomeric, subtelomeric Antenatally diagnosed cases of CHD should be investigated
and whole chromosome painting probes are available. for karyotyping and for 22q11.2 deletion syndrome. Increased
NT, IUGR and other non-cardiac malformations of 22q11.2
GEnEtiC CounSElinG deletion syndrome should be screened carefully for thymus
hypo or aplasia and fetal echo for cardiac defects including
Genetic counseling is a communication process to aid people vascular ring. Chromosome analysis along with the FISH
understand and adapt to the medical, psychological and studies to be carried out in patients with the DGS/VCFS
familial implications of genetic contributions to disease. This spectrum. Other chromosomal abnormalities can help in
process integrates the following-interpretation of family and detecting new gene loci similar to all other genes, which were
medical histories to assess the chance of disease occurrence identified based on chromosomal abnormality. Even though
or recurrence, understanding alternatives for dealing with the deletion on 10p is relatively rare deletions of DGSI and
recurrence risk, choosing a course of action best suited to the DGSII result in similar phenotypes, and hence, it is still
112 patient based on their values and family goals and to make beneficial to screen patients referred for DGS and VCFS for
DGSII loci, if DGSI is normal.54 Recent studies also suggest ACknowlEDGmEnt 6
that mutation in GATA4 and NKX2-5 are responsible for CHDs
and may not be the microdeletion. We wish to thank Dr I B Vijayalakshmi, Professor of Pediatric
http://vip.persianss.ir
1 18. Ramegowda S, Ramachandra NB. An understanding the genet-
ic basis of congenital heart disease. Indian Journal of Human
36. Reamon-Buettner SM, Cho SH, Borlak J. Mutations in the
3'-untranslated region of GATA4 as molecular hotspots for
Genetics. 2005; 11:14-23. congenital heart disease (CHD). BMC Med Genet. 2007; 8:38.
Embryo to thE NEoNatE
19. Chaoui R, Korner H, Bommer C, et al. Prenatal diagnosis of 37. Lubs ML, Lubs HA. Chromosome identification-techniques
heart disease and associated chromosomal aberrations. Ultra- and applications in biology and medicine. Nobel Symposia.
schall Med. 1999; 20:177-84. 1973; 8:241-50.
20. Burn J, Goodship J. Cong. heart disease. In Emery and 38. Bröcker-Vriends AH, Mooij PD, van Bel F, et al. Monosomy
Rimoin’s: Principles and Practice of Medical Genetics, Rimoin 8p: an easily overlooked syndrome. J Med Genet. 1986; 2:
DL, Connor MJ, Pyeritz RE, Korf BR (Eds), 4th edn, Churchill 153-54.
livingstone, Chapter 2002; 47,1:1239-72. 39. Devriendt K, Fryns JP, Mortier G, et al. The annual incidence
21. Tézenas Du, Montcel S, Mendizabai H, et al. Prevalence of of DiGeorge/velocardiofacial syndrome. J Med Genet. 1998;
22q11 microdeletion. J Med Genet. 1996; 33:719. 35:789-90.
22. Devriendt K, Fryns JP, Mortier G, et al. The annual incidence 40. Pehlivan T, Pober BR, Brueckner M, et al. GATA4
of DiGeorge/velocardiofacial syndrome. J Med Genet. 1998; Haploinsufficiency in Patients With Interstitial Deletion of
35:789-90. Chromosome Region 8p23.1 and Congenital Heart Disease.
23. Botto LD, May K, Fernhoff PM, et al. A population-based study American Journal of Medical Genetics. 1999; 83:201-06.
of the 22q11.2 deletion: phenotype, incidence, and contribution 41. Reddy KS. A paternally inherited terminal deletion, del(8).
to major birth defects in the population. Pediatrics. 2003; (p23.1) pat, detected prenatally in an amniotic fluid sample: a
112:101-07. review of deletion 8p23.1 cases. Prenat Diagn. 1999; 19:868-
24. Carelle-Calmels N, Saugier-Veber P, Girard-Lemaire F, et al. 72.
Genetic compensation in a human genomic disorder. N Engl J 42. Bhatia SN, Suri V, Bundy A, et al. Prenatal detection and
Med. 2009; 360:1211-16. mapping of a distal 8p deletion associated with congenital
25. Shiojima I, Komuro I, Inazawa J, et al. Assignment of cardiac heart disease. Prenatal Diagn. 1999; 19:863-67.
homeobox gene CSX to human chromosome 5q34. Genomics. 43. Devriendt K, Matthijs G, Van Dael R, et al. Delineation of
1995; 27:204-6. the critical deletion region for congenital heart defects, on
26. Harvey RP. NK-2 Homeobox genes and heart development. chromosome 8p23.1. Am J Hum Genet. 1999; 64:1119-26.
Dev Bio. 1996; 178:203-16. 44. Claeys I, Holvoet M, Eyskens B, et al. A recognizable
27. Dentice M, Cordeddu V, Rosica A, et al. Missense mutation behavioral phenotype associated with terminal deletions of the
in the transcription factor NKX2-5: A novel molecular event short arm of chromosome 8. Am J Med Genet. 1997; 74:515-
in the pathogenesis of thyroid dysgenesis. J Clin Endocrinol 20.
Metab. 2006; 91:1428-33. 45. Fryns JP, Kleczkowska A, Vogels A, et al. Normal phenotype
28. Turbay D, Wechsler SB, Blanchard KM, et al. Molecular and slight mental retardation in de novo distal 8p deletion
cloning, chromosomal mapping and characterization of the (8pter–8p23.1). Ann Genet. 1989; 32:171-73.
human cardiac-specific homeobox gene hCsx. Molec Med. 46. Hutchinson R, Wilson M, Voullaire L. Distal 8p deletion (8p23.
1996; 2:86-96. 1–pter): a common deletion. J Med Genet. 1992; 29:407-11.
29. Pauli RM, Scheib-Wixted S, Cripe L, et al. Ventricular non- 47. Wu BL, Schneider GH, Sabatino DE, et al. Distal 8p deletion
compaction and distal chromosome 5q deletion. Am J Med (8p23.1): An easily missed chromosomal abnormality that
Genet. 1999; 85:419-23. may be associated with congenital heart defect and mental
30. Gibbons B, Tan SY, Kee SK, et al. Interstitial deletion of retardation. Am J Med Genet. 1996; 62:77-83.
chromosome 5 in a neonate due to maternal insertion, ins(8; 5). 48. Giglio S, Graw SL, Gimelli G, et al. Deletion of a 5-cM
(p23; q33q35). Am J Med Genet. 1999; 86:289-93. region at chromosome 8p23 is associated with a spectrum of
31. Schafer IA, Robin NH, Posch JJ, et al. Distal 5q deletion congenital heart defects. Circulation. 2000; 102:432-67.
syndrome: phenotypic correlations. Am J Med Genet. 2001; 49. Bourrouillou G, Colombies P, Gallegos D, et al. Partial
103:63-68. monosomy 10p in a case investigated with tomodensitometry.
32. Schiffer C, Popp S, Moshir S, et al. Multicolor chromosomal Ann Genet. 1981; 24:61-64.
bar coding characterizes a de novo interstitial deletion (5) 50. Schuffenhauer S, Seidel H, Oechsler H, et al. DiGeorge
(q33.3q35.2) in a child with multiple congenital malformations. syndrome and partial monosomy 10p: case report and review.
Clin Dysmorphol. 2003; 12:129-31. Ann Genet. 1995; 38:162-67.
33. Baekvad-Hansen M, Tümer Z, Delicado A, et al. Delineation of 51. Daw SC, Taylor C, Kraman M, et al. A common region of
a 2.2 Mb microdeletion at 5q35 associated with microcephaly 10p deleted in DiGeorge and velocardiofacial syndromes. Nat
and congenital heart disease. Am J Med Genet. A. 2006; Genet. 1996; 13:458-60.
140:427-33. 52. Schuffenhauer S, Lichtner P, Peykar-Derakhshandeh P.
34. Rauch A, Dörr HG. Chromosome 5q subtelomeric dele- Deletion mapping on chromosome 10p and definition of
tion syndrome. Am J Med Genet C Semin Med Genet. 2007; a critical region for the second DiGeorge syndrome locus
145C:372-76. (DGS2). Europ J Hum. Genet 1998; 6:213-25.
35. Bjørnstad PG, Leren TP. Familial atrial septal defect in the 53. Lichtner P, Konig R, Hasegawa T, et al. An HDR
oval fossa with progressive prolongation of the atrioventricular (hypoparathyroidism, deafness, renal dysplasia). syndrome
conduction caused by mutations in the NKX2.5 gene. Cardiol locus maps distal to the DiGeorge syndrome region on
Young. 2009; 19:40-44. 10p13/14. J Med Genet 2000; 37:33-37.
114
54. Berend SA, Spikes AS, Kashork CD, et al. Dual-probe 72. Chen M, Hwu WL, Kuo SJ, et al. Subtelomeric rearrangements
and 22q11.2 deletion syndrome in anomalous growth-restricted
6
fluorescence in situ hybridization assay for detecting deletions
associated with VCFS/DiGeorge syndrome I and DiGeorge fetuses with normal or balanced G-banded karyotype.
http://vip.persianss.ir
1 91. Fuchs F, Riis P. Antenatal sex determination. Nature. 1956;
177: 330.
96. Percutaneous umbilical cord blood sampling (2010). wikipedia.
org. <http://en. wikipedia. org/wiki/Percutaneous_umbilical_
92. Woo J (2002). “A short History of Amniocentesis, Fetoscopy cord_blood_sampling>[Retrived on 2012-30-06].
Embryo to thE NEoNatE
and Chorionic Villus Sampling”. ob-ultrasound. net. <http:// 97. Jung Mde P, Cardoso MH, Villar MA, et al. Revisiting
www. ob-ultrasound. net/amniocentesis. html> [Retrieved on establishments of the etiology of Turner syndrome. Hist Cienc
2012-30-06]. Saude Manguinhos. 2009; 16:361-76.
93. Ferguson-Smith M, Bianchi DW. Prenatal Diagnosis: past, 98. Wolstenholme J, Rooney DE. Cytogenetics in the 1970s and
present, and future. Prenat Diagn. 2010; 30:601-04. 1980s. Prenat Diagn. 2010; 30:605-07.
94. Hobbins JC, Mahoney MJ. In utero diagnosis of haemoglobino- 99. Pardue ML, Gall JG. Molecular hybridization of radioactive
pathies. Technique of obtaining fetal blood. N Engl J Med. DNA to the DNA of cytological preparations. Proc. Natl. Acad.
1974; 290:1065. Sci. USA. 1969; 64:600-04.
95. Alfirevic Z, Walkinshaw SA and Kilby MD (2010). Green-top 100. Harper ME, Saundres GF. Localization of single copy DNA
Guideline No. 8 Aminiocentesis and Chorionic Villus Sampling sequences on Gbanded human chromosomes by in situ
from Royal College of Obstetricians Guidelines,<http://www. hybridization. Chromosoma. 1981; 83:431-9.
rcog. org. uk/womens-health/clinicalguidance/amniocentesis- 101. Resta R, Biesecker BB, Bennett RL, et al. National society of
and-chorionic-villus-sampling-green-top-8>[Retrieved on genetic counselors' definition task force. J Genet Couns. 2006;
2010-20-10]. 15:77-83.
116
Sec t i on
Basics
http://vip.persianss.ir
Examination of the Heart—
C hapter
7 A Comparative External
and Internal Anatomy
Pradeep Vaideeswar
Understanding the normal anatomy of the heart forms an further dissection or operative techniques. The features to
important basis in the diagnosis of various congenital and be seen on external examination would be the orientation,
acquired diseases of the heart through investigative modalities. cardiomegaly, appearance of anterior and posterior surfaces,
Examination of the external surface of the heart often provides chamber and vascular morphology and appearance of the
clues to the inner pathology, which may alter the pattern of epicardial surface.
Figure 1A Figure 1B
Most pathologists or for that matter even anatomists are guilty within the thorax by the systemic and pulmonary venous
of using inappropriate descriptive terms in the gross analysis connections. The axis of the ventricles is tilted laterally
as we continue to orient the heart in an upright position like a to the left from base to apex, extending anteriorly and
‘valentine’ heart. slightly inferiorly; the atrioventricular junction follows the
This is the true anatomic position of the heart. The ventricular orientation.
atrial have an anteroposterior relationship and are fixed
http://vip.persianss.ir
2 EXTERNAL SuRfACES
Anterior (figure 2)
BAsics
Figure 2
The anterior surface of the heart shows the right and left atrial appendages (RAA, LAA) and the great arteries (Ao—Aorta,
PT— pulmonary trunk) towards the base and most of the right ventricle (RV) and small part of the left ventricle (LV) towards
the apical aspect. The atria and ventricles are separated by their respective atrioventricular grooves that are filled with adipose
tissue (which increase with age and/or weight of the patient). The apex points to the left and is formed by LV. The normal great
arterial relationship is constituted by anterior and left position of PT, relative to ascending aorta. The surface anatomy of left
anterior descending artery (LAD) offers an excellent guide to position of interventricular septum.
Posterior (figure 3)
In the external anatomy, the most characteristic features of the atria are their appendages. The RAA is large and triangular with a
broad base. It is to be noted that the entire anterior atrial wall is formed by the appendage, which is characteristically pectinated.
The caval veins enter the right atrium (RA) at an obtuse angle
or nearly in alignment with superior vena cava (SVC) being
anterior to the IVC. Demarcating the extensively pectinated
appendage from a smooth walled venous component of RA
is sulcus terminalis (dotted line). Important in this area is the
location of sinoatrial or SA node. This is an elliptical structure
(black ellipse), which occupies a lateral position at superior
cavoatrial junction. It sits as a wedge of specialized tissue
subepicardially, not occupying the full thickness of atrial wall.
Rarely, it is disposed in a horse-shoe shape at the junction or
may be discernible to the naked eye. 121
Figure 5
http://vip.persianss.ir
2 Left Atrial Morphology (figures 6 and 7)
BAsics
Figure 6A Figure 6B
In contrast to RAA, LAA resembles a crooked little finger with crenellations and a distinctive narrow junction with main atrial
chamber. It is located more superiorly than RAA, overlying the left main coronary artery to reach the root of the PT.
Figure 9
The above figure 9 shows the relationship of various structures at the base of the heart. 123
http://vip.persianss.ir
2 Cardiomegaly (figures 10A and B)
BAsics
The heart may be small in size, normal or enlarged. The cardiomegaly may be graded as mild, moderate or marked. More
importantly, it is important to assess the chamber or chambers responsible for the change. On the right image, there is mild
cardiomegaly, but there is marked enlargement of the RV so that the interventricular septum (as delineated by LAD, arrows) is
pushed towards the left and even the apex is formed by RV. The epicardial surface is inspected for the presence of increase in
adipose tissue, thickening, tortuosity of coronary vasculature and presence of fluid or exudates.
INTERNAL ANATOMY
Figure 13
Figure 15
http://vip.persianss.ir
2 Atrioventricular Valves (figures 16 and 17) Ventricles (figures 18 to 22)
Figure 16
Figure 18
The TV has three leaflets: anterior (ATL), septal (STL) and The RV is coarsely trabeculated with a thin compact portion
posterior (PTL) and hence three commissures: anteroseptal, that measures 0.5 to 0.7 cm. The trabeculation extends even
posteroseptal and anteroposterior. The leaflets are anchored to into the outflow tract.
the RV endocardium via the chordae tendineae to the papillary
muscles. The anterior group is constant, while the posterior is
usually developed and the medial is occasionally developed.
Figure 17
The mitral valve (MV) has two leaflets: anterior (AML) and
Figure 19
posterior (PML) and two commissures: anterolateral and
posteromedial. The AML has a greater width and appears a The LV is finely trabeculated with a thick compact portion
little tongue-shaped. The subvalvular apparatus is represented measuring about 1 cm. The septal surface is smooth and
by delicate chords attached to fairly constant anterior and covered by the thicker endocardium (Measurements: Usually
126 posterior group of papillary muscles. taken 1 cm below the arterial valves).
7
http://vip.persianss.ir
2 Arterial Valves (figures 23 and 24)
The arterial valves are described with respect to their annuli,
BAsics
Figure 24
128
C hapter
Classification of Cardiovascular
8 Anomalies and their Terminologies
http://vip.persianss.ir
2 to the nearby anatomy (including the stomach, liver, spleen, drain into both right and left atrium.3 In situs ambiguous the
and bronchi).3 Three different anatomic configurations may stomach can be either on the left, right or in the midline.
be observed: situs solitus (normal), situs inversus (inverted
Basics
A B C D
130 Figures 1A to D: Schematic diagram showing the various characteristic features of different types of thoraco-abdominal situs:
A. Situs solitus; B. Situs inversus; C. Right isomerism; D. Left isomerism
When the morphologic right ventricle is on the right side 8
of the morphological left ventricle, the bulboventricular loop
is defined as ‘D’ (dextro) loop. When the morphological
Great Arteries
Two great arteries, i.e. aorta and pulmonary artery normally
arise from the left and right ventricles respectively. Valves of
these vessels cannot be differentiated by their structure. The
vessels are identified by their branching pattern. Aorta as it
ascends, gives rise to three branches from the arch, while the
main pulmonary trunk bifurcates early into two pulmonary
arteries. Aortic sinuses are also identified by recognizing
the origin of the coronary arteries from them. The problem
Figure 2: Coronal image of computed tomographic angiogram in a comes when only one arterial trunk is identified. It could be
2-year-old girl with left isomerism shows bilateral long, thin, curved due to atresia of one of the major great vessels, i.e. aortic
left bronchus (2 black arrows) with polysplenia indicated by 3 white atresia or pulmonary atresia. Common arterial trunk or
arrows. (Image courtsey: Dr Madhav Hegde) truncus arteriosus is defined as the vessel which arises from
the ventricle and has a common arterial valve. It supplies the
coronary, systemic and pulmonary arteries directly. In one of
visceral situs and orientation of the vessels at the diaphragm the types of truncus (type IV), the pulmonary trunk is absent
should be clearly defined. and the pulmonary blood supply comes from the collaterals
arising from the descending aorta. Such a type of arterial trunk
Ventricles is called solitary arterial trunk.4
The characteristic differentiating features of right and
Normal ventricle has three parts: inlet, trabecular and outlet. left atrium, ventricles and the two great arteries are given in
Inlet portion has the atrioventricular valve, its tension apparatus Box 1.5
including the papillary muscles. Trabecular portion extends
from the papillary muscles to the apex. Outlet portion is the part Atrioventricular Junction and
of ventricle from apex to the valves leading to the great vessels. Atrioventricular Valves
Trabecular portion of the ventricles differentiates the two
ventricles for identification. The right ventricle has coarse Atrioventricular junction is the union of atrium and ventricle
trabeculations whereas left ventricle has got fine trabeculations and its analysis will involve atrial arrangement with respect
and is smooth walled. to left and right atrium, their connections to ventricles
Atrioventricular valves always go with the ventricles, i.e. and morphology of the valves. Morphological left and
tricuspid valve will always be with the right ventricle and right atrium in respect to each other may be lateralized-
mitral valve with the left ventricle. Identification of valves meaning morphological left atrium is located to the left and
helps in defining the morphology of the ventricle. Tricuspid morphological right atrium is on right side or they could be
valve is identified by typical attachment of the septal leaflet mirror image, where they are located on opposite sides or
to the interventricular septum. Mitral valve does not have any there may be isomerism.
attachment to the septum. Its anterior and posterior leaflets are The atrioventricular valve is formed of fibrous tissue and
attached with the two papillary muscles within the ventricle. connects the atrium to the ventricle. Valves tend to travel
At the atrioventricular level, tricuspid valve is positioned along with their respective ventricles, thus tricuspid valve will
more closer to the apex in comparison to the mitral valve. always be present with the morphological right ventricle and
This feature is very well-defined in the four chamber view of mitral valve will always be with morphological left ventricle. 131
echocardiography. If morphological left atrium is connected to the morphological
http://vip.persianss.ir
2 Box 1: Morphological features of various cardiac chambers and great arteries
Basics
Atria
Right atrium Left atrium
Appendage Triangular Finger-like
Appendageal orifice Wide Narrow
Sulcus and crista terminalis Yes No
Pectinate muscles Extend to atrioventricular junction Do not extend to atrioventricular
junction
Fossa ovalis with limbus Yes No
Ventricles
Right ventricle Left ventricle
Trabeculation Heavy and irregular Fine and relatively regular
Trabecular septomarginalis Yes No
Moderator band Yes No
Septal attachment of the atrioventricular More apical More basal (cranial)
valve
Chordal attachment to the IVS Yes No
Great Arteries
Aorta Main pulmonary artery
Course Long arching Branching
Branches Origin of coronary arteries Pulmonary arteries
Cephalic and other systemic arteries
IVS = Interventricular septum
left ventricle then this connection is called concordant, while tricuspid valve atresia and mitral valve atresia has evolved
if this connection is inappropriate, means left atrium is for malformed hearts where one of these valve is atretic. In
connected to the morphological right ventricle and vice versa, such univentricular hearts, the corresponding ventricle, i.e.
it is called discordant.6 in tricuspid atresia, right ventricle or in mitral valve atresia,
The morphology of atrioventricular valves should be the left ventricle may be hypoplastic. The connection can be
defined well. One of the two atrioventricular valves may be discordant also in cases where the atrium can be connected
absent, while in another situation there can be overriding and to a dominant left or dominant right ventricle. Rudimentary
straddling. Both straddling and overriding are associated with ventricles are usually malformed and their morphology
ventricular septal defects. In straddling, the atrioventricular is defined by explaining the morphology of the dominant
valve has part of its chordal apparatus attached across the ventricle. Thus, if the dominant ventricle is morphologically
ventricular septum into the other ventricle, while in overriding left ventricle, hypoplastic ventricle will be the right ventricle
only the opening of the valve sits across the septal crest. only.
Malformed hearts where both the atria connect with only
one ventricle is categorized under univentricular connections. Ventriculoarterial Junction
Most of such cases have two ventricles, but only one ventricle
is of normal size and has inlet, body and outlet components. Ventriculoarterial junction is the junction of ventricles and
In such cases, the other ventricle is hypoplastic and usually arterial segments, where the connections could be concordant
lacks the inlet portion. Larger ventricle may be morphological or discordant. Concordant connection is when the aorta is
right ventricle or morphological left ventricle and respectively arising from the left ventricle and the pulmonary trunk is
named as double-inlet right ventricle or double-inlet left arising from the right ventricle. Discordant connection is
ventricle. when these vessels are arising from the opposite ventricles.
Similarly in the group of univentricular connections, one Transposition is a term used when the great vessels have
132 of the atrioventricular valve may be atretic and thus one of discordant connection with regard to the ventricle. The
the atria is not connected with the ventricle. Thus, the term combination of concordant atrioventricular connection and
8
Figure 3: Types of human heart: segmental sets and alignments. Heart diagrams are viewed from below, similar to a subxiphoid two-
dimensional echocardiogram. Cardiotypes depicted in broken lines had not been documented when this diagram was made. The aortic
valve is indicated by the coronary ostia; the pulmonary valve is indicated by the absence of the coronary ostia. Braces { } mean “the set
of.” The segmental sets are explained in the text. Rows 1–4 and 6 have ventriculoarterial (VA) concordance. Row 5, transposition of the
great arteries, has VA discordance. Rows 7 and 8 have double-outlet RV and LV, respectively. Columns 1 and 3 have atrioventricular
(AV) concordance, {S, D, -} and {I, L, -}, respectively. Columns 2 and 4 have AV discordance, {S, L, -} and {I, D, -}, respectively. Ant
= Anterior; Inf = Infundibulum; L = Left; LA = Morphologically left atrium; LV = Morphologically left ventricle;. Post = Posterior; R = Right;
RA = Morphologically right atrium; RV = Morphologically right ventricle; (Courtesy: From Foran RB, Belcourt C, Nanton MA, et al. Isolated
infundibuloarterial inversion {S, D, I}: a newly recognized form of congenital heart disease. Adapted from Am Heart J 1988;116:1337–1350, with 133
permission)
http://vip.persianss.ir
2 discordant ventriculoarterial connection gives rise to complete Complete transposition of the great arteries in an abbreviated
transposition of great vessels. The combination of discordant form can be described as (S, D, D ), i.e. S = situs soilitus,
connection at atrioventricular junction and discordant D = D loop, D = D transposition. Similarly, after segmental
Basics
ventriculoarterial connection (double discordance) gives rise analysis, all types of segmental connections can be described
to congenitally corrected transposition. in an abbreviated form (Figure 3).9 It is important that the
When both the great arteries arise from one ventricular description of complex cardiac anomalies in whatever way we
chamber, the ventriculoarterial connection is considered do, should be easier to understand and describe.
as double outlet. It can be from right ventricle or from left
ventricle. Defining the associated malformations
Morphology of ventricular outflow tract is different in
left and right ventricle. Right ventricular outflow tract has Sequential segmental analysis defines the chambers of the
muscular infundibulum, while there is fibrous continuity heart and the connections of various segments of the heart,
between the arterial and atrioventricular valve in the left but many a times, associated malformations are the ones
ventricle. who have a major impact on the clinical presentation.10
The spatial relation of both the great vessels to each other Apart from defining the position of the heart in the chest and
also needs to be defined. Two trunks usually have spiral defining the apex pointing to left or right, pulmonary venous
relation, but can be parallel to each other in transposition anomalies, various types of atrial septal defects, anomalies of
physiology. Anteroposterior and right-left relation of aortic atrioventricular valves, ventricular septal defects, anomalies
and pulmonary valves to each other also requires to be defined, of aortic arch and coronary anomalies, etc. They also require
as this would help in surgical management. to be defined well for complete diagnosis and management.
135
http://vip.persianss.ir
C hapter
9 Cardiac Malpositions
Sejal Shah
Cardiac malposition is defined as the location of the heart The morphological right atrium is to the right and morpho-
anywhere other than its usual position in the left hemithorax logical left atrium is to the left or the morphological right
or location of the heart in the left hemithorax when other atrium is to the right and posterior and the morphological
organs are in an abnormal position such as situs inversus. left atrium is to the left and anterior, hence the term situs
Cardiac malpositions include dextrocardia, mesocardia, solitus, pivoted is used.2 The morphological left ventricle
isolated levocardia, pericardial defects and ectopia cordis. is relatively anterior and right ventricle lies to the right. It
is frequently associated with atrioventricular discordance.
Dextrocardia
Embryology
Incidence
At 22 to 23 days of gestation, the primitive cardiac loop normally
Dextrocardia is defined as a right-sided heart with a base bends towards the right forming a D-loop (the morphological
apex axis directed rightward resulting from a variation in right ventricle is to the right of morphological left ventricle)
cardiac development and not used as a general term indicating (Figure 1A). During the next 10 to 12 days, the apex of the
any heart in the right chest.1 The malposition is intrinsic heart gradually migrates from the right side of the thorax to its
to the heart and not caused by extracardiac abnormalities. normal location in the left hemithorax. Lack of this normal left
Dextrocardia should be differentiated from secondary cardiac ward migration of the cardiac mass explains the development
dextroposition, which is defined as displacement of the heart of dextrocardia with situs solitus (dextroversion). Conversely,
to the right secondary to extracardiac causes such as right lung in situs inversus with L-loop (Figure 1B), the apex of the heart
hypoplasia, right pneumonectomy or diaphragmatic hernia.2 swings from the left hemithorax to the right, which explains
Dextrocardia occurs in approximately 0.01 percent of live the development of dextrocardia with situs inversus. Failure of
births1 and 0.008 percent of pregnancies.3 In a retrospective the shift of the apex of the heart to right hemithorax in L-loop
review of all cases of dextrocardia, the number of cases of can result in the development of levocardia with situs inversus
situs solitus, situs inversus and isomerism were found to be (levoversion). If the shift of the apex remains incomplete, it
similar.3 Cardiac malformations were more common in the results in mesocardia.
situs solitus (96%) and isomerism group (100%) compared
to situs inversus group (25%).3 Cardiac malformations were Clinical Presentation
complex in the situs solitus and isomerism groups.3
Incidental detection is common with mirror image dextrocar-
Types dia in normal intracardiac anatomy on chest X-ray done as
a screening test or for other medical disorders. In rest of the
1. Dextrocardia mirror image: This is true dextrocardia situations, the intracardiac anatomy would decide the type of
occurring with abnormal situs (situs inversus or ambiguous), presentation.
most common of which is situs inversus totalis. Physical appearance: Poland syndrome is reported with
2. Dextroversion dextrocardia: This type of dextrocardia situs solitus dextrocardia. It has absence of a pectoralis major
occurs with situs solitus. Here, the cardiac apex fails to pivot muscle, ipsilateral syndactyly, brachydactyly and hypoplasia
to the left and the heart appears to have twisted to the right. of a hand.4 Goldenhar syndrome is reported with complete
9
Cardiac Malpositions
A B
Figures 1A and B: A. The primitive heart tube normally loops to the right forming a D-bulboventricular loop, which is associated with heart being
in the left hemithorax; B. If the loop is to the left, it results in a L-bulboventricular loop where the apex of the heart swings from the left thorax to
the right. LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle
http://vip.persianss.ir
2 atrium to the right of morphological left atrium, the major axis
of the heart is normal, to the left.
The position of the transducer is important to obtain the
Basics
Cardiac Malpositions
A
B
Figures 3A and B: Electrocardiogram in a 8-year-old with situs inversus, dextrocardia. A. P wave is negative in lead one and aVL and upright
in lead aVR with absent R wave progression in left precordial leads; B. Right precordial leads show the progression of the R wave
A B C
Figures 4A to C: Subcostal 4 chamber view on echocardiogram showing. A. The apex of heart to the left side indicating levocardia; B. The
apex of heart to the right side indicating dextrocardia; C. The apex of heart appears to be in the midline with vertically positioned interventricular
septum, which is characteristic of mesocardia
high incidence of ASD, has an association with a litany Scimitar syndrome can present in infancy with severe
of cardiovascular anomalies including ventricular septal symptoms, i.e. respiratory distress and severe pulmonary
defect, patent ductus, hypoplastic aortic arch, coarctation, arterial hypertension and has worse prognosis or can 139
tetralogy of Fallot, anomalous origin of the left coronary present in older children with recurrent respiratory tract
artery and truncus arteriosus.11 infections and a murmur.
http://vip.persianss.ir
2
Basics
D
Figures 5A to D: Shows probe positions for mirror image dextrocardia. A. Subcostal 4 chamber view is done in the conventional way;
B. Apical view is obtained by placing the transducer on the right side of chest, in fifth or sixth intercostal space near the anterior axillary line with
the plane of sound directed in a similar way as subcostal 4 chamber; C. Parasternal long axis view is obtained at the right second-third intercostal
space, the plane of sound is oriented from the left shoulder to the right hip; D. Parasternal short axis has the plane of sound from right shoulder
to the left hip and is obtained by rotating 90° clockwise from parasternal long axis view
140
Table 1
situs solitus, though situs inversus and ambiguous has also 9
Clues to differentiate types of dextrocardia on echocardiogram been seen. The types of the heart found in mesocardia are
same as those found in dextrocardia and levocardia.17
Cardiac Malpositions
Dextroposition Dextroversion Dextrocardia
RA, RV on right RA, RV on right LA on the right of Isolated levocardia
side of LA, LV side of LA, LV RA
Major axis of heart Major axis of heart Major axis of heart When there is situs inversus or heterotaxy with levocardia,
pointing left from left shoulder from left shoulder it is considered a malposition. Isolated levocardia is rare.
to right hip to right hip The morphological right atrium is to the left and posterior
Entire heart to Apex to right of Apex in right fifth and the morphological left atrium is to the right and anterior,
right of midline/ midline intercostal space hence the term situs inversus, pivoted is used.2 Most of these
retrosternal
cases have been found to have atrioventricular discordance,
Transducer to right, PLAX plane in PLAX and PSAX in ventriculoarterial discordance or double outlet right ventricle
usual orientation of mirror image, mirror image
and right anterior aorta.8,18
plane PSAX normal
orientation
LA = Left atrium; LV = Left ventricle; PLAX = Parasternal long axis view; PSAX
Congenital pericardial defects
= Parasternal short axis view; RA = Right atrium; RV = Right ventricle
Congenital defects of pericardium are uncommon and difficult
to diagnose clinically. They are commonly detected as an
2. Situs inversus with dextrocardia is known to have much unexpected finding during surgery or autopsy. The incidence
less incidence of intracardiac abnormalities. It usually was found to be 0.044 percent among patients who underwent
occurs without coexisting congenital heart disease.12 cardiovascular surgery.19 Pericardial defects are due to
Associated anomalies included ventricular septal defect, defective formation of the pleuropericardial membrane or
tetralogy of Fallot, pulmonary atresia, complete atrioven- septum transversum.20
tricular septal defect, secundum ASD and atrioventricular It could range from minor partial defects to total absence of
concordance with ventriculoarterial discordance.13 Atriov- the pericardium.20 Two types of congenital pericardial defects
entricular with ventriculoarterial discordance is rare, but have been described: a complete form where there is absence
when present is associated with ventricular septal defect of the pericardium on one side of the heart, left or right and
with pulmonary stenosis.13 Rarely, isolated ventricular a partial form, where the defect is localized to a certain area
inversion is seen (atrioventricular discordance with ven- of the heart. Complete agenesis is not compatible with life.
triculoarterial concordance).13 Left-sided pericardial defects are more common.20,21 Right-
However, they are at a greater risk for pulmonary sided defects, diaphragmatic defects and total absence are
diseases than the general population. The most common of rare. Pericardial defects have been described with congenital
these is ‘Kartagener syndrome’ (KS). KS is an autosomal cardiac defects,19,22–24 though it is unlikely that they share the
recessive disorder14 characterized by dextrocardia, same pathogenic mechanisms.
bronchiectasis, sinusitis15 and infertility.16 The genetic cause for abnormal development of pericardium
is not clear. GATA4 gene is considered a candidate gene for
Treatment pericardial defects.25
http://vip.persianss.ir
2 In partial left-sided defects, there can be herniation of with decrease in the severity and frequency of pain in all
the ventricles through the patent pleuropericardial foramen patients after surgery.26
resulting in strangulation of the ventricles and sudden death or
Basics
Cardiac Malpositions
immotile cilia syndrome. New Eng J Med. 1978; 298:282.
ectopia cordis.46
17. Lev M, Liberthson RR, Golden JG, et al. The pathologic
anatomy of mesocardia. Am J Cardiol. 1971; 28:428-35.
Conclusion 18. Stanger P, Rudolph AM, Edwards JE. Cardiac malpositions:
An overview based on study of sixty-five necropsy specimens.
A sequential segmental approach with an understanding of the Circulation. 1977; 56:159-72.
possible malpositions with their associations would greatly 19. Vas Son JAM, Danielson GK, Schaff HV, et al. Congenital
facilitate the diagnosis of congenital heart disease. partial and complete absence of the pericardium. Mayo Clin
Proc. 1993; 68:743-7.
The doctor is often more to be feared than the disease. 20. Southworth H, Stevenson CS. Congenital defects of the
pericardium. Arch Intern Med. 1938; 61:223-40.
—French Proverb
21. Ellis K, Leeds NE, Himmelstein A. Congenital deficiencies
in the parietal pericardium: A review with 2 new cases
References including successful diagnosis by plain roentgenography. Am J
Roentgenol Radium Ther Nucl Med. 1959; 182:125.
1. Evans WN, Acherman RJ, Collazos JC, et al. Dextrocardia: 22. Nasser WK, Helmen C, Tavel ME, et al. Congenital absence
Practical clinical points and comments on terminology. Pediatr of the left pericardium. Clinical, electrocardiographic,
Cardiol. 2010; 31:1-6. radiographic, hemodynamic and angiographic findings in six
2. Bharati S, Lev M. Positional variations of the heart and its cases. Circulation. 1970; 41:469-78.
component chambers. Circulation. 1979; 59:886-7. 23. Skalski J, Wites M, Haponiuk I, et al. A congenital defect of the
3. Bohun CM, Potts JE, Casey BM, et al. A population-based pericardium. Throac Cardiovasc Surg. 1999; 47:401-4.
study of cardiac malformations and outcomes associated with 24. Drury NE, De Silva RJ, Hall RMO, et al. Ann Thorac Surg.
dextrocardia. Am J Cardiol. 2007; 100:305-9. 2007; 83:1552-3.
4. Fraser FC, Teebi AS, Walsh S, et al. Poland sequence with 25. Jay PY, Bielinska M, Erlich JM, et al. Impaired mesenchymal
dextrocardia: Which comes first? Am J Med Genet. 1997; 73:194. cell function in GATA4 mutant mice leads to diaphrag
5. Gorgu M, Aslan G, Erdooan B, et al. Goldenhar syndrome with matic hernias and primary lung defects. Develop Biol. 2007;
situs inversus totalis. Int J Oral Maxillofac Surg. 1998; 27:404. 301:602-14.
6. Snider AR, Serwer GA, Ritter SB. Diagnostic approach to 26. Gatzoulis MA, Munk MR, Merchant N, et al. Isolated congenital
Complex Congenital Heart Disease. In: Echocardiography in absence of pericardium: Clinical presentation, diagnosis and
Pediatric Heart Disease 2nd edition; 1997. p. 560. management. Ann Thorac Surg. 2000; 69:1209-15.
7. Calcaterra G, Anderson RH, Lau KC, et al. Dextrocardia: value 27. Khoury MJ, Cordero JF, Rasmussen S. Ectopia Cordis, midline
of segmental analysis in its categorisation. Br Heart J. 1979; defects and chromosome abnormalities: An epidemiologic
42:497. perspective. Am J Med Genet. 1988; 30:811-7.
8. Van Praagh R, Van Praagh S, Vlad P, et al. Diagnosis of anatomic 28. In: Skandalakis JE, Gray SW, Ricketts R, Skandalakis JE, Gray
types of Dextrocardia. Am J Cardiol. 1965; 15:234-43. SW, (eds). Embryology for surgeons. 2nd edition. Baltimore:
9. Lev M, Liberthson RR, Eckner FAO, et al. Pathologic anatomy Williams and Wilkins; 1994. pp. 552-9.
of dextrocardia and its clinical implications. Circulation. 1968; 29. Blatt ML, Zeldes M. Ectopia Cordis: Report of a case and
37:979-99. review of the literature. Am J Dis Child. 1942; 63:515.
10. Van Praagh R, Vlad P. Dextrocardia, mesocardia and 30. Byron F. Ectopia Cordis: report of a case with attempted
levocardia: The segmental approach to diagnosis in congenital operative correction. J Thorac Surg. 1949; 17:717-22.
heart disease. In: Keith JD, Rowe RD, Vlad P (Eds). Heart 31. Leca F, Thibert M, Khoury W, et al. Extrathoracic heart (ectopia
Disease in Infancy and Childhood. 3rd edition. New York: cordis). Report of two cases and review of the literature. Int J
Macmillan; 1978. p. 638. Cardiol. 1989; 22:221-8.
11. Gudjonsson U, Brown JW. Scimitar Syndrome. Semin Thorac 32. Cantrell JR, Haller JA, Ravitch MM. A syndrome of
Cardiovasc Surg Pediatr Card Surg Ann. 2006; 9:56-62. congenital defects involving the abdominal wall, sternum,
12. Merklin RJ. Cardiac lesions associated with visceral inversion: diaphragm, pericardium and heart. Surg Gynecol Obstet.
A study of 185 cases. J Int Coll Surg. 1964; 4:597. 1958; 107:602-14.
13. Van Praagh R, Weinberg PM, Smith SD, et al. Malpositions 33. Laberge JM. Defination of pentalogy of Cantrell. Commentary
of the heart. In: Adams FH, Emmanoulides GC, on Araujo Junior et al: diagnosis of pentalogy of Cantrell by
Riemenschneider TA, (Eds). Heart Disease in Infants, three-dimensional ultrasound in third trimester of pregnancy
Children and Adolescents. 4th edition, Baltimore: Williams (Fetal Diagn Ther 2006; 21:544-7). Fetal Diagn Ther. 2008;
and Wilkins; 1989. p. 530. 23:168.
14. Gorham GW, Merselis JG Jr. Kartagener’s triad: a family 34. Kaplan LC, Matsuoka R, Gilbert EF, et al. Ectopia cordis and
study. Bull Johns Hopkins Hosp. 1959; 104:11-6. cleft sternum: Evidence of mechanical teratogenesis following
15. Kartagener M, Horlacher A. Zur pathogenese der rupture of the chorion or yolk sac. Am J Med Genet. 1985;
Bronchiektasien; Situs viscerum inversus and polyposis nasi 21:187-99.
143
http://vip.persianss.ir
2 35. Van Allen MI, Myhre S. Ectopia Cordis thoracalis with
craniofacial defects resulting from early amnion rupture.
41. Bick D, Markowitz RI, Horwich A. Trisomy 18 associated with
ectopia cordis and occipital meningocele. Am J Med Genet.
Teratology. 1985; 32:19-24. 1988; 30:805-10.
Basics
36. Bieber FR, Mostoufi-zadeh M, Birnholz JC, et al. Amniotic 42. Fox JE, Gloster ES, Mirchandani R. Trisomy 18 with Cantrell
band sequence associated with ectopia cordis in one twin. J Pentalogy in a still born infant. Am J Med Genet. 1988; 31:
Pediatr. 1984; 105:817-9. 391-4.
37. Amato JJ, Zelen J, Talwalkar NG. Single stage repair of 43. King CR. Ectopia Cordis and chromosomal errors. Pediatrics.
thoracic ectopia cordis. Ann Thorac Surg. 1995; 59:518-20. 1980; 66:328.
38. Hornberger LK, Colan SD, Lock JE, et al. Outcome of patients 44. Soper SP, Roe LR, Hoyme HE, et al. Trisomy 18 with ectopia
with ectopia cordis and significant intracardiac defects. cordis, omphalocele and ventricular septal defect. Case report.
Circulation. 1996; 94:32-7. Pediatr Pathol. 1986; 5:481-3.
39. Hochberg J, Ardenghy MF, Gustafson RA, et al. Repair of 45. Garson A, Hawkins EP, Mullins CE, et al. Thoracoabdominal
thoracoabdominal ectopia cordis with mucocutaneous flaps ectopia cordis with mosaic Turner’s syndrome. Report of a
and intraoperative tissue expansion. Plast Reconstr Surg. 1995; case. Pediatrics. 1978; 62:218-21.
95:148-51. 46. Morales JM, Patel SG, Duff JA, et al. Ectopia cordis and other
40. Diaz JH. Perioperative management of neonatal Ectopia midline defects. Ann Thorac Surg. 2000; 70:111-4.
cordis: report of three cases. Anest Analg. 1992; 75:833-7.
144
c hapter
10 Heterotaxy syndrome
http://vip.persianss.ir
2 bending and septation of cardiac loop and conotruncus, cardiac development because development of spleen, division
growth of endocardial cushion, location of lungs, rotation of of atrioventricular canal and the conotruncus, somewhat
gut, pulmonary venous connection to the roof of left atrium coincide in fetal life.1–6,21–24 The polysplenia initially was
BASIcS
(LA) and development of spleen takes place.9,10 overlooked as a marker of one more subset of HS till Moller
Over 100 genes have been identified as important in left- et al (1967) published another breakthrough paper of their own
right asymmetry in animal models.11–17 The heterogeneity findings and correlated it with previously published literature.
of genes related to HS, combined with a prediction of They found that these polysplenic patients had a tendency for:
reduced penetrance and variable expressivity, makes clinical 1. Cardiac malposition.
molecular diagnostics challenging. Patients with Trisomy 2. Interruption of inferior vena cava (IVC) with azygos
13 or Trisomy 18 have been reported to have heterotaxy. A continuation.
number of submicroscopic chromosomal deletions, including 3. Partial or total anomalous pulmonary venous connection to
22q11.2 (DiGeorge/velocardiofacial syndrome [VCFS]), have the venous atrium.
been identified in patients with heterotaxy.11,12 The majority 4. Bilateral superior vena cava
of mutations identified have been shown to have reduced 5. Defects in the atrial and ventricular septa
penetrance and variable expressivity, indicating multifactorial Additionally, they reported presence of extracardiac
causation. Environmental modifiers such as maternal diabetes, abnormalities that was:
maternal cocaine use and monozygotic twinning have all been 1. Partial or complete abdominal heterotaxy
associated with heterotaxy spectrum defects.15 2. Abnormality of pulmonary lobulation
The X-linked form of heterotaxy, HTX-1 (OMIM# :306955) 3. Symmetrical liver.23
is caused by mutations in a zinc finger transcription factor, These evolutionary findings fueled further debate regarding
ZIC3. X-linked heterotaxy, caused by mutations in ZIC3, is the the terminology of HS and splenic morphology.
best understood genetic cause of heterotaxy.16,17 Interestingly, The terminological address of spectrum of HS evolved
mutations in this gene can cause classic heterotaxy or isolated slowly. Evidently it needed a large numbers of publications
congenital heart defects. In one family, three of nine female and extensive discussions to reach to a consensus so that
carriers exhibited situs inversus. Approximately, 1 percent of current nomenclature and terminology could prevail.1–6
sporadic heterotaxy cases (male and female) and greater than
75 percent in familial X-linked heterotaxy cases are due to controversies in nomenclature25–27
ZIC3 mutations.17
Heterotaxy patients without mutations in ZIC3 have been It had been the convention over the years to describe these
screened for mutations in genes involved in the conserved characteristic groups of HS in terms of asplenia and polysplenia.
nodal signal transduction pathway.18 The mutations have been Afterwards, it was clear that these splenic morphological
identified in genes encoding the ligand (NODAL), ligand abnormalities are vacillating, henceforth cannot be reckoned
coreceptor (CFC-1), receptor (ACVRIIB), transcriptional co- as a sole pennant of HS. Subsequently, attention was drawn
activator (FOXH1) and midline inhibitor (LEFTYA) within towards the unique morphological resemblance of two
the nodal signal transduction pathway.12,19 atrial appendages (Figures 1A to C). Umera and Anderson
The PCD disorders are characterized by abnormalities et al highlighted that description of the morphology of the
of ciliary structure and function and are most commonly appendages as well as the venoatrial connections, were more
autosomal recessive. Heterotaxy with PCD is caused by conclusive than anything else. As it was pointed out by Van
mutations in DNAH5 and DNAH11 genes.20 Praagh, Anderson’s group themselves changed their stand
later, by advocating the inner anatomy of appendages as the
HIstorIcal background and nomenclature basis of diagnosis rather than the outer morphology. Now
there is a consensus regarding the description of HS on the
“…asplenia, is a teratologic syndrome of visceral symmetry…” broader basis rather than diagnosing it as right atrial (RA) or
— Ivemark 195522 LA isomerism and isomerism of atrial appendages is to be
accepted as a real anatomic entity (See Box 1).
The first case on record of this combination of anomalies
is that of Martin (1826), who described the necropsy findings recommendations of nomenclature Working group for
of a case of septal defect, transposition of the great vessels Pediatric and congenital Heart disease (2007)6
and agenesis of the spleen. In 1955, Biorn Ivemark (1955)
published his landmark paper, which included analyses This group reviewed the nomenclature, definition and
of all the cases from the published literature, as well as his classification of heterotaxy and emphasized more on sequential
own 14 cases, in which he postulated that it was possible to segmental analysis (Table 1). The few of the recommendations
have teratogenic effect of some genetic factor on splenic and are as follows:
146
10
HeTeRoTAxy SyndRome
A B
c
Figures 1A to c: Computed tomography (CT) angiography 3D reconstruction: A. Normal right and left atrial appendages in a case of situs solitus,
dextrocardia, corrected transposition of the great arteries (TGA); B. Bilateral right atrial appendage in dextrocardia with corrected TGA and;
C. Isomerism of left atrial appendage. (Courtsey: Apoorva Goyal, Francis B). LAA = Left atrial appendage; RAA = Right atrial appendage.
Table 1
Nomenclature and segmental analysis in heterotaxy5,6,25,27
Segments Variables
Atrial situs S (solitus), I (inversus), A (ambiguous) X (unknown)
Ventricular loop D (right handedness), L (Left handedness), X (unknown)
Arterial relationship N (normal), S (solitus), I (inversus), D (D-malposed), L (L-malposed), A (anterior aorta), X (unknown)
AV connection Concordant, discordant, biventricular and mixed, double inlet and absent connections (right or left),
univentricular heart
AV valve Two perforate valves, one single perforate valve with an absent atrioventricular connection, one perforate
along with one imperforate valve, a common valve or an absent valve with a so-called unguarded orifice,
straddling of valve, overriding of valve >50%, 50–90%, >90%
VA connection Concordant, discordant, single outlet (common arterial trunk), single outlet via aorta (pulmonary atresia),
single outlet via pulmonary trunk (aortic atresia, DOLV, DORV)
VA valve Over-riding, imperforate valve, absent AV/PV
Cardiac position/apex Dextrocardia, levocardia, mesocardia, dextroversion, levoversion, bifid apex
AV = Atrioventricular; DOLV = Double outlet left ventricle; DORV = Double outlet right ventricle; PV = Pulmonary valve; VA = Ventriculoatrial. 147
http://vip.persianss.ir
2 1. Description of cardiac and non-cardiac thoracoabdominal either of the groups. Discordant ventricular apex and stomach
structures: The cardiac anatomy and associated cardiac relationship predicts a complex CHD.
malformations, as well as the relationship and arrangement
BASIcS
HeTeRoTAxy SyndRome
Figure 2: Inferior vena cava (IVC) and abdominal aorta (Ao) at the level of diaphragm defining atrial situs (L1 vertebra).
ILAA = Isomerism of left atrial appendage; IRAA = Isomerism of right atrial appendage.
Atrial Anatomy1,5,6,21–31 has an extensive junction with the vestibule of the RA; the
later structure is the smooth-walled atrial myocardium that
The RA has three basic parts: the appendage, the vestibule inserts into the leaflets of the tricuspid valve. The most
and the venous component. The right atrial appendage has the characteristic and constant feature of the morphology of the
shape of a blunt triangle, with a wide junction to the venous RA is that the pectinate muscles within the appendage extend
component across the terminal groove. The appendage also around the entire parietal margin of the atrioventricular (AV) 149
http://vip.persianss.ir
2 junction. The venous component of the RA extends between
the terminal groove and the interatrial groove. It receives
the superior and inferior caval veins and the CS. The RA is
BASIcS
HeTeRoTAxy SyndRome
A B
Figures 4A and B: Isomerism of; A. Right atrial appendage, left-sided (HV) draining into left-sided atria. B. Left atrial appendage, ascending
azygos vein beside the descending aorta drains into right superior vena cava (RSVC). (Courtsey: Apoorva Goyal, Francis A)
The most common abnormality found in HS is common In ILAA, partial or transitional AVSD with two distinct AV
AV junction or the so called atrioventricular canal defect orifices, is common. However, presence of normal AV junction
(AVCD). This has also been called endocardial cushion defect with or without shunt lesions is not uncommon in ILAA.
or atrioventricular septal defect (AVSD). These defects Cardiac structure in ILAA may be completely normal or may
have varying degrees of incomplete development of the AV have simple heart defects. VSD is the usual finding in HS.
septal tissue adjacent the AV valves along with spectrum In IRAA, preponderance of common AV junction
of abnormalities of the AV valves themselves. Partial predisposes for a true large inlet VSD, but other types of
AVSD or incomplete AVSD has an ostium primum ASD isolated or additional defect like, perimembranous, outlet,
and abnormal left AV valve. Typically the left AV valve doubly committed and muscular, can be present.
in this subset differs from the normal MV. It is guarded In ILAA, an inlet VSD may be present as a part of AVSD.
by three leaflets and has a cleft essentially facing the IVS. Because common AV junction in this group usually manifest
Complete AVSD (CAVSD) has both defects in the atrial as partial or transitional AVSD, inlet VSDs is less frequent in
septum just above the AV valves (ostium primum ASD) and comparison to the IRAA. Other varieties of VSD can be seen
defects in the ventricular septum just below the AV valves. in this group.
In CAVSD, the AV valve is one valve that bridges both the
right and left sides of the heart, creating superior (anterior) outflow in Heterotaxy5,23–25,36,37
and inferior (posterior) bridging leaflets. Transitional or
intermediate AVSD is in-between and has two distinct The conotruncal abnormalities are frequent associations of
orifices, but also has an ASD just above and a ventricular HS. The outflows can be obstructed, partially or completely in
septal defect (VSD) just below the AV valves. The VSD both IRAA and ILAA.
in this lesion is often restrictive. The AV valves in all the IRAA, is usually associated with right ventricular outflow
three forms may be grossly abnormal, often regurgitant and tract (RVOT) obstruction and pulmonary valve anomaly.
prognosticate a suboptimal surgical outcome. In ILAA, on the contrary, the left ventricular outflow tract
In IRAA, CAVSD and common AV valve with common (LVOT) obstruction is common.
orifice is frequently associated. The tethering and type of Besides, both the groups in HS may be associated with
straddling of the superior and inferior bridging leaflets abnormal ventriculoarterial connection like transposition and
forms the hemodynamic basis for complex AV connections, double outlet right or left ventricle (Table 2).
abnormal flow pattern, resulting in developmentally
unbalanced ventricles. Sometimes, in the absence of AVSD, Conduction System
various degree of overriding, straddling of AV valves may lead
to serious consequences. The aforesaid complex intracardiac Patients with IRAA may be associated with bilateral
anatomy is the substrate for univentricular or Fontan type sinoatrial (SA) node. However bilateral presence of SA node
repair in majority of cases of IRAA. is not a universal finding as was shown by Ware et al who
151
http://vip.persianss.ir
2 demonstrated the presence of bilateral sinus nodes in only AV node is seen or a sling of conduction tissue is seen along
54 percent of the cases.38 the crest of IVS, connecting an anterior and posterior AV node.
In ILAA, bilateral absence of sinus nodes is seen frequently. Pattern is almost same when RV is the dominant ventricle, but
BASIcS
Ware et al documented bilateral absence of SA node in if LV is dominant with RV as a small ventricle, the AVN is
25 percent of cases with left isomerism.38 anterior and lies in relation to the LVOT.4,5
The pathways for AV conduction in hearts with isomerism
of the atrial appendages are conditioned both by ventricular Coronary Arteries in Heterotaxy
topology and by the AV connections. No pathognomonic
variation is seen in HS. Umera et al reported abnormal patterns in branching of the
In D-loop ventricle, an AV node is in its regular position, coronary arteries, associated with abnormal ventricular
with a posteroinferior penetrating bundle, which is further architecture. The morphologically LV/RV arteries were
posteriorly deviated in presence of AVSD. In L-loop ventricle, frequently lacking in those hearts with a dominant ventricle
the conduction system simulates to that of congenitally and a rudimentary or incomplete ventricle. A solitary coronary
corrected transposition of great vessels, i.e. either an anterior artery was seen in 13 percent of cases.39
Table 2
Usual morphological features in heterotaxy
Clinical and morphological Isomerism of left atrial appendage Isomerism of right atrial appendage
features
Heart position Levocardia: 50–75% dextrocardia: 2–10% Levocardia: 63%, rest dextro or mesocardia
Systemic veins Absence of intrahepatic portion of IVC with Bilateral SVC: 50–60% cases and absent
azygos/ hemiazygos venus system continuation coronary sinus in 78% cases.
to SVC. Hepatic veins may form confluence
and drain into right/left sided atrium or in the
floor of common atrium in 90–96% of cases.
Bilateral SVC: 40% cases and absent coronary
sinus in 30–55% cases.
Pulmonary veins PAPVC: 40–60% with ipsilateral veins draining TAPVC > 50%, up to 40% case have
into respective atrial chamber. TAPVC 10–12% obstructed vertical vain
usually due to malalignment of atrial septum.
Scimitar syndrome 1%
Atria Both atrial appendages are both atrial Both atrial appendages are both atrial
appendages are morphological LAA: Long appendages are morphological RAA: Broad
narrow and pectinate muscles restricted upto base, thumb like in little anterior plane and
the base of appendage and not going beyond. pectinate muscle extending beyond the base
No crista terminalis, fossa ovalis is often of appendage.
absent. Large ostium primum defect in 50–65% Bilateral crista terminalis, fossa ovalis is
cases. However, fenestrated fossa ovalis, intact often absent. Common atrium or large ostium
atrial septum, sinus venosus ASD also have primum defect in majority of the cases, isolated
been reported. or as a component of complete AVSD.
Atrial septum/atrioventricular Common AV junction, partial AVSD with two Common AV valve associated with complete
(AV) junction/valve distinct AV orifices and cleft in left component or partial AVSD 80–90%. Common atrium
of AV valve. Ostium primum ASD is frequent where single strand runs through cavity or a big
as a part of partial AVSD. Other kind of ASDs secundum ASD along with ostium primum ASD
(secundum/sinus venosus can also be seen. (like common atrium) has been reported.
AV connection Univentricular connection: 10–40% Univentricular connection > 72%
RVOT/LVOT Pulmonary stenosis/atresia: 28–30% Pulmonary stenosis/atresia: Up to 80–90%,
LVOTO: 40% (coarctation of aorta 16%; LVOTO uncommon
AS 10%)
VA connection Are abnormal in 50% patients. TGA: 16%, Abnormal ventriculoarterial connection—
DORV: 32%, DOLV: 7% discordant, double oulet or single outlet:
90–96%
Significant CHD Less frequent > 98%
Conduction system Sinus node may be absent There may be two sinus node
152
Contd...
Contd... 10
Clinical and morphological Isomerism of left atrial appendage Isomerism of right atrial appendage
HeTeRoTAxy SyndRome
features
Lungs and bronchi Symmetrical, left bronchus and left lung Symmetrical, right bronchus and right lung
morphology bilaterally (90%) (trilobed) morphology bilaterally (90%)
Congenital lobar pneumonia
Spleen Majority multiple (88%), absent (5%); single in Majority-absent (80%) few: single (17%)
few multiple (4%)
Liver Symmetrical (25–70%), right-sided Symmetrical (majority of cases)
or left-sided
Stomach May be placed in center, right or left May be placed in center, right or left
hypochondrium hypochondrium
Bowel Malrotation of gut, volvulus Malrotation of gut, short dorsal mesentery:
Short mesentery-13% other abnormality: jejunal 19%. Cephalic migration of colon
atresia
Duplication of bowel
Pancreas Truncated/annular can be seen more often Rare
Gallbladder Biliary atresia 11% usually biliary abnormalities Usually no biliary abnormalities
are seen like mirror image branching,
quadruplicating or ciliary atresia, cholelithiasis
Percentages listed are approximations based on review of references22,29–31,34,36–39,49,50,52,53
ASD = Atrial septal defect; AVSD = Atrioventricular septal defect; DOLV = Double outlet left ventricle; DORV = Double outlet right ventricle; IVC = Inferior
vena cava; LAA = Left atrial appendage; LVOTO = Left ventricular outflow tract obstruction; PAPVC = Partial anomalous pulmonary venous connection;
PS/PA = Stenosis or atresia; RAA = Right atrial appendage; RVOT/LVOT = Right/left ventricular outflow tract; SVC = Superior vena cava; TAPVC = Total
anomalous pulmonary venous connection; TGA = Transposition of the great arteries; VA = Ventriculoarterial.
Other Cardiopulmonary Manifestations In IRAA, the lungs are trilobed bilaterally and are connected
in Heterotaxy Syndrome to eparterial bronchi. Both the branches of pulmonary artery
show the morphological pattern of right PA as they travel
Many other cardio-pulmonary anomalies like pulmonary below and anteroinferior to the bronchus on both the sides to
hypertension and portopulmonary shunt, have been described enter into the respective hilum. The corresponding bronchus
but can not be associated consistently with HS. There are enters underneath the PA after giving rise to its first branch
isolated reports of association of pulmonary emphysema, (eparterial branch). The ratio of the length of bronchi measured
non-compacted LV, scimitar syndrome, isolated pulmonary from bifurcation of trachea to the origin of first branch from
sequestration and bronchomalacia, mostly in ILAA group.40–43 bronchus, remains <1.5.
In ILAA, both the bronchi have the same length and the
anatomical arrangement and structure of extracardiac first branch of both the bronchi arise most distally (hyparterial
thoracoabdominal organs in Heterotaxy bronchus), after they pass beneath the respective branch PA.
Hence, branch PA are the morphological left PA, bilaterally.
Predictively, the lungs are bilobed and isomeric in this setting.
Lungs and Bronchial Anatomy43–45 Van Meirope et al suggested that the chest roentgenogram
The ratio between left (bronchus sinister) and right in anteroposterior or posteroanterior view can be best way
bronchial (bronchus dexter) length is usually 2 : 1. Also the of knowing atrial situs, as it always corresponds to tracheo-
branch pulmonary arteries (PAs) are in a unique relationship bronchial tree.44 This conventional thinking is not valid
with the ipsilateral bronchi. Accordingly, the first branch of absolutely and evidences to contrary, i.e. atriobronchial
the right bronchus can be described as ‘eparterial or that discordances, are cropping up.44–47
of the left bronchus as hyparterial’.45–47 The lungs differ Yet, in clinical settings, loss of bronchopulmonary
from each other in the number of their lobes, consequently asymmetry is most easily discernible and useful clue to the
the bronchi differ in their mode of subdivision (Figures 5A diagnosis of HS.
to D). The right lung has three lobes, one oblique and one In a recent publication, the five thoracic features in 306
horizontal fissure. The left lung has two lobes, one major postmortem specimens were assessed to evaluate broncho-
oblique fissure. These features can be appreciated in plain atrial relationship and its validity as a marker of atrial situs. 153
chest roentgenogram.45–47 The results showed a good, but variable predictive value of
http://vip.persianss.ir
2
BASIcS
A B
c d
Figures 5A to d: Computed tomography (CT) angiography reconstruction: A. Isomerism of right bronchus. Distance of the origin of first bronchus
bilaterally. Early branching; B. Isomerism of left bronchus. Delayed origin of first branch; C. Isomerism of right atrial appendage:: pulmonary
artery (PA) branches (white arrow) passing anterior to both bronchus till the first branch of bronchus originates; D. Isomerism of left atrial
appendage:: Pulmonary artery first branch arising before the first branch of bronchi and crossing over the bronchus. (Courtesy: Apoorva Goyal,
Mr Francis)
each criterion. Morphological features of bronchi, lungs and Morphology of spleen in ILAA5,6,48–54: The splenic mass
branch pulmonary artery are given in Table 3. is usually divided into fairly equally sized 2 to 6 masses or
splenules. Usually these splenules are 1 to 6 cm in diameter,
abdomen in Heterotaxy which together equals to the mass of a normal spleen
(Figure 6). Infrequently, there may be several small spleens
adjacent to either one or two larger spleens. The location of
Liver 5,6,24–26,49,50
these splenules may be along the greater curvature of the
The liver normally has two lobes. The right lobe is usually stomach, in the left or right upper quadrant of abdomen. A
approximately six times larger than the left. It occupies the single-bilobed spleen is a rare variant. The polysplenia results
right hypochondrium, The left lobe is smaller and more from incomplete fusion of the splenic mesenchymal tissue. We
flattened than the right. It is situated in the epigastric and left will discuss functional status of the spleen later in the chapter.
hypochondriac regions. The liver in HS, is often centrally
placed or may remain in right or left hypochondrium. malrotation of gut
HeTeRoTAxy SyndRome
Morphological features Percentage of positive prediction
(Specimen: 306; heterotaxy: 56)
Lung lobation 77%
Lengths of main bronchi 77%
Ratio of left to right (L/R) 90%
bronchial lengths (<1.5)
Relationship of bronchi to > 95%
ipsilateral pulmonary artery
Number of cartilage rings in 77%
each main bronchus
http://vip.persianss.ir
2
BASIcS
A B
Figures 7A and B: A. Barium meal. Malrotation of gut. Right-sided stomach, duodenojejunal (DJ) junction to the left;
B. MRI scan. Truncated pancreas (ILAA). Part of body and tail is missing. Area is empty near splenic artery
No characteristic clinical finding can be narrated, as, a 3. Abnormal left axis deviation.
number of intracardiac abnormalities are associated with the HS. 4. Abnormal Q waves (single ventricle or ventricular
According to intracardiac anomaly clinical findings will vary. inversion).
5. Accessory pathway.
routine Work-up The atrial situs, ventricular hypertrophy patterns can
be assessed by evaluating axis and voltage of P, QRS and
According to the severity of symptoms, a detailed clinical T waves. In postoperative period, one can see varieties of
as well as laboratory work-up must be planned to ascertain rhythm abnormalities (Figure 8A).
the cardiac diagnosis and to see the functional status of renal, The characteristic ECG of ILAA shows an aberrant P-wave
hepatic, splenic and other systems. axis, progressive slow heart rate, multiplicity of atrial rhythm,
AV block and junctional escape rhythm. Overall complete AV
chest radiograph: Predictors of asplenia syndrome block is observed in one-tenth of cases of left isomerism.5,60
Figure 8B shows low atrial focus in a patient with ILAA.
Besides providing the usual information on cardiopulmonary This patient underwent a double switch operation successfully,
status, there are certain findings in chest X-ray which suggests but had a slow junctional rate postoperatively. The patient
the presence of HS. needed a permanent pacemaker implantation.
Trinavarat et al evaluated six such findings in a series of In IRAA, ECG may show multiple atrial rhythms and
30 prediagnosed patients of asplenia syndrome and found a variable P-wave axis. The changing P-wave axis is due to
bilateral minor fissure in 53 percent, bilateral eparterial bilateral sinus node with switching over of pacemaker function.
bronchi in 53 percent, symmetrical transverse liver in 30 In few cases, there might be dual QRS axis due to the
percent, ipsilateral side of liver and stomach in 30 percent, presence of dual AV node and sling of conduction tissue. Re-
ipsilateral side of minor fissure or eparterial bronchus and entry tachycardia can be seen in these circumstances.
stomach in 33 percent, contralateral side of minor fissure or One of the case series consisting of cases with ILAA
eparterial bronchus and liver in 23 percent. They found atleast showed mean frontal P-wave axis of −30° to −90° in 70
two positive findings in 28 out of 30 patients.58 percent of subjects. Additionally, in half of the cases, atrial
rate was below the second percentile. Only 10 percent cases
electrocardiogram5,59,60 had it persistently low. About 40 percent of cases showed a
tendency for recurrence. The junctional escape rhythm was
Electrocardiogram in HS must be evaluated for rate, rhythm, seen in 42 percent.60
accessory pathways and AV conduction. The abnormalities in ECG may also be related to
Usual ECG abnormalities are: intracardiac defects and QRS axis may deviate superiorly with
1. Abnormal P-wave axis (bilateral SA node or absent SA a counterclockwise or clockwise loop and may show abnormal
node and position of atria). ventricular dominance. An abnormal cardiac rhythm can also
156 2. Bradycardia/junctional rhythm/blocks. be noticed in fetal life.61
10
HeTeRoTAxy SyndRome
A
B
Figures 8A and B: A. Postfontan IRAA supraventricular tachycardia and; B. ECG in ILAA: a junctional beat follows
the atrial ectopic then low atrial foci is taking over
Echocardiography is the best modality to understand The computed tomography (CT) scan and angiography
anatomical and hemodynamic effects of the prevalent are used routinely for complex HS. The radiation to the
structural heart diseases in HS. It can be done by transthoracic babies and children remains a constant worry. Otherwise, it
or transesophageal route. Numerous series of images can be requires less time for acquisition of images unlike magnetic
displayed through multiple windows. Since the orthogonal resonance imaging (MRI) or conventional angiography.
planes of the heart are different from the major axes of the Our own experience with this modality is excellent. CT
body, it is conventional to describe the window of access as gives outstanding 2D and 3D imaging of atrial appendages,
well as the reference plane. The availability of the subcostal systemic and pulmonary veins, aorta and its branches,
windows in babies and small children are a great advantage, collaterals and pulmonary arteries. Additional morphological
because they enable the examiner to produce innumerable information about the bronchial anatomy, lung lobulation and
sequential images in desired orthogonal planes and hence position of the abdominal viscera can be obtained accurately.
provide opportunity to follow the anatomical course of veins The abdominal contrast CT is also needed to understand gut
and arteries, to study atrial and ventricular septum despite morphology (Refer: Figures 1A to C; 3A and B; 4A and B; 6
their obliquity and to identify the diverse placement of the and 7A and B).64,65
cardiac valves.
The diagnosis of HS by echocardiography is based on the magnetic resonance Imaging
abnormal placement of the descending aorta and IVC in the
subcostal short-axis view. We have seen that this relationship MRI gives excellent images of the cardiovascular system. It
is unpredictable at times. The identification of morphology can create moving images of the heart throughout its pumping
of the atrial appendages is not possible always (Figures 9A cycle. Therefore, unlike the CT scan, MRI can do a functional
to F). assessment of the heart. It can demonstrate abnormalities
157
http://vip.persianss.ir
2
BASIcS
A B
c d e F
Figures 9A to F: Echocardiography in heterotaxy syndrome: A. Atrial situs: IRAA. Juxtaposed (IVC)/Abdominal Ao on right side of spine; B. Atrial
situs: ILAA. Interrupted IVC/Az continuation; C. IRAA, complete (AVSD). Indeterminate ventricle; D. Subcostal modified coronal view. Common
(AV) valve; E. ILAA. Interatrial septum. (ASD) secundum; F. ILAA. Left SVC to roof of LA. Coronary sinus is absent
HeTeRoTAxy SyndRome
A B
Figures 10A and B: Post-extracardiac Fontan surgery: LPA stenting in a 13-year-old boy
http://vip.persianss.ir
2
Table 4
Medical management of heterotaxy syndrome (cardiac disease*)72–76
BASIcS
critical baby with congestive heart failure Decongestives, diuretics, digoxin, ACE inhibitors. Fluid restriction.
Blood transfusion, if required. Refer to PA banding, if required. BAS, if
transposition is suspected.
Recognition and treatment of fulminant sepsis Prompt recognition of infection. Investigate and treat with appropriate
antibodies.
* Other system must be evaluated, a cyanosed baby may be critical because of non-cardiac problems like volvulus.
** Surgical emergency.
techniques have increased the number of patients undergoing ventricle (DORV) (3/91), tetralogy of Fallot (TOF) in
either univentricular or biventricular repair. 3.2 percent (3/91) and hemitruncus in 2.1 percent (2/91).
Noritaka Ota et al reported a retrospective review of Operations included double switch repair, physiologic repair,
institutional database from 1997 to 2010 and recognized 60 arterial switch and the Rastelli procedure. Separation of
consecutive patients with IRAA having single ventricle. They systemic from pulmonary venous return included intra-atrial
found that 5-year survival was 53.8 percent before 2003 and baffle in 48/91 patients and extracardiac grafting in 2/91.
81.7 percent after 2004 (p = 0.035) and identified persistent Average follow-up was 44.9 plus or minus 57.5 months
AV valve regurgitation of more than moderate degree (p = (3 days–189.3 months). Kaplan-Meier estimated survival
0.04) as a factor associated with late mortality.86 was 93.4% at 10 years; unbalanced complete AV canal was
One of the recently published retrospective studies has shown the only risk factor for mortality (P = .006). Subsequent
increased postoperative morbidity and mortality in 87 patients procedures were common with a 10-year freedom from
with CHDs with HS in comparison to that of CHDs without reoperation or reintervention of 38% ± 7.5%. Arrhythmias
HS. They found prolonged postoperative hospital stay (17 : 11 occurred in 36 (39.6%) patients; bradyarrhythmia in 27
days), prolonged mechanical ventilation (11 : 4 days), increased (29.7%) and tachyarrhythmia in 15 (16.5%). Freedom from
number of tracheostomies (6.9% : 1.6%), increased use of any arrhythmia was 53.9% plus or minus 6.7% at 10 years.88
ECMO (12.6 : 4.9%) and postsurgical deaths (16.1 : 4.7%).87 These results are better than the previously published
series about surgical outcome in patients with ILAA. In
bIventrIcular rePaIr In Heterotaxy syndrome— the series published by Gilljam et al, 87 percent cases
a surgIcal cHallenge underwent biventricular repair and combined 15 years
survival was less than 50 percent.77 This difference may be
To achieve biventricular repair in IRAA is a surgical challenge. due to patient selection strategies because incriminated risk
Nevertheless, world over, the recent trend amongst the factors had been congenital AV block, aortic coarctation,
surgeons is to attain a biventricular repair, whenever possible. single ventricle, billiary atresia and other gastrointestinal
Lim et al reported the series of 371 patients with HS. malformations.77,79,84,88
91/371 (24.5%) patients underwent biventricular repair from
1990 to 2007. Median age at repair was 6.8 months with a PreventIve strategIes and Prenatal dIagnosIs
range of 5 days to 22 years. LA isomerism was present in
73% (66/91) and right atrial isomerism in 10 percent (9/91), The genetic testing and counseling has some role to play, but a
with indeterminate atrial anatomy in 17 percent (16/91). definitive primary preventive strategy is yet to be found. When
Combined lesions were common, occurring in 99 percent we discuss the outcome of HS, the possibility of diverse outcome
of patients, which included systemic venous anomalies always pre-exists. Additionally, the risk of sepsis in asplenic
in 82 percent (75/91), pulmonary venous anomalies in patients or abnormal ciliary system in ILAA may influence
160 28 percent (26/91), endocardial cushion defects in 39 the outcome. Antenatal fetal echocardiography is the solitary
percent (36/91), transposition complexes 16 percent (15/91), preventive strategy in routine use. The natural elimination by
AV discordance in 10 percent (10/91), double outlet right spontaneous abortion has been noticed in many studies.
Berg et al examined their database retrospectively and found Streptococcus pneumoniae is the most common patho- 10
that in 32 of 35 fetuses had prenatal diagnosis of cardiosplenic gen causing septicemia in asplenic children followed by
syndromes. 22 fetuses had left isomerism. Their main prenatal Haemophilus influenzae, Neisseria meningitidis, Staphyloco-
HeTeRoTAxy SyndRome
ultrasound features were interrupted IVC (n = 21), CAVSD ccus aureus and other streptococci.
(n = 15), viscerocardiac heterotaxy (n = 15), persistent The splenic malfunction is diagnosed by presence of target
bradyarrhythmia (n = 12) and fetal hydrops or nuchal edema cells, Howell-Jolly, Heinz, Pappenheimer bodies and pitted
(n = 12). 12 pregnancies were terminated, 2 fetuses were erythrocytes in peripheral smear. The pits or pox on the red
stillborn and 8 infants survived. 10 fetuses had right isomerism. cell surface, ability to clear 51Cr-labeled heat damaged red
Their main sonographic features were juxtaposition of cells, SPECT-CT done with 99mTc-labelled, heat altered
the descending aorta and IVC (n = 7), CAVSD (n = 7), left autologous erythrocyte scintigraphy are the advanced methods
persistent SVC (n = 6) and viscerocardiac heterotaxy (n = 6). In to know the functional status of spleen.96,97
this group there was 1 stillbirth, 5 infant deaths and 4 survivors.
They suggested that diagnosis of left isomerism should be long-term management of asplenia/Hyposplenia76–80
strongly suggested in the presence of a combination of at least
two of the following: The four component of medical management are:
1. Complete atrioventricular septal defect or other structural 1. Antibiotic prophylaxis.
heart disease. 2. Appropriate immunization.
2. Interruption of IVC with azygos continuation. 3. Very aggressive management of suspected infection.
3. Early fetal heart block. 4. Parent education.
4. Viscerocardiac heterotaxy. Identification notes and written instructions must be
Right isomerism should be suspected in the presence of a given to asplenic patients (Box 2). The recommendations are
combination of at least two of the following:
1. Structural heart disease, namely CAVSD.
2. Juxtaposition of IVC and descending aorta.
3. Viscerocardiac heterotaxy.89 Box 2: Asplenia or hyposplenia: Prophylaxis against
Lin et al reported a series of 25 fetal diagnoses who were bacterial infection97–101
diagnosed and managed on the basis of antenatal diagnosis.90,91
• Universal immunization of IRAA patients with the
However, in their series isomerism of left atrial appendage
pneumococcal conjugate (PCV7) below 2 years and/or
was twice as common as isomerism of right atrial appendage. polysaccharide vaccine (PPC23) above 2 years and influenza
vaccine can improve the morbildity.81 Reimmunization is
Heterotaxy In adultHood recommended for children who received pneumococcal
vaccine before 24 months of age
It is rare to have adult patients afflicted with HS probably • Children up to 5 years should also receive all doses of
Haemophilus influenzae type b vaccine. Unimmunized
because severity of malformations makes them less capable to children >5 years should receive 1 dose
endure life. However, few of case reports and small case series • Patients should also receive quadrivalent meningococcal
have been reported. Majority of these patients had ILAA and vaccine.
less severe cardiac malformations.49,92,93 Antibiotic prophylaxis
• Regardless of vaccination status, children with splenic mal-
functIonal status of sPleen In function must be on antibiotic prophylaxis before 2-month
Heterotaxy syndrome94–101 of age. Oral administration of penicillin V potassium is
recommended at a dosage of 125 mg twice a day until
The association of IRAA with asplenia leads to deficient 3-year of age and at a dosage of 250 mg twice a day after
3-year of age. Children who have not experienced invasive
body defense mechanism. Besides, absence or inappropriate pneumococcal infection and have received recommended
functional abilities of spleen in ILAA are also known. pneumococcal immunizations may discontinue penicillin
Thus, functional evaluation of the spleen is mandatory in prophylaxis after 5-year of age.
heterotaxy syndrome for an appropriate management plan. • Some experts recommend that asplenic patients have
The functional evaluation of spleen, bacterial prophylaxis and access to ‘stand-by’ antibiotics (Amoxicillin with or without
infection control protocols are guided by experience gained in clavulanic acid), which can be initiated with higher doses
schedule at the first sign of infection (fever, chills or
splenectomized patients. malaise). The initiation of ‘stand-by’ antibiotics is not a
substitute for seeking immediate medical attention at the
effect of asplenia/Hyposplenia94–95 onset of an illness cannot be overemphasized.79–80
• Asplenic patients have a high-risk to develop severe
Risk of bacteremia is highest in absence of spleen. The bacteria malaria with very high peripheral blood parasite counts.
transmitted by human or animal bite, protozoal infestations They should be given appropriate prophylaxis if travelling 161
to endemic areas.
like malaria or babesiosis can be dangerous.
http://vip.persianss.ir
2 extrapolation of the guidelines for the patients who underwent 5. Steven A, Umera H, Anderson RH. Paediatric Cardiology,
Isomerism of atrial appendages. 3rd edition editors-Anderson
spleenectomy for some medical reasons.
RH, Baker EJ, Redington A, Rigby ML, Penny D, Wernovsky
BASIcS
HeTeRoTAxy SyndRome
disease associated with polysplenia: a developmental complex 40. Brandenburg VM, Krueger S, Haage P, et al. Heterotaxy
of bilateral ‘left-sidedness’. Circulation. 1967; 36(5):789. syndrome with severe pulmonary hypertension in an adult.
24. Stanger P, Rudolph AM, Edwards JEZ. Cardiac malpositions: South Med J. 2002; 95(5).
an overview based on study of 65 necropsy specimens. 41. Mohan KK, Kramer N, Margolis ML, et al. Intralobar pulmo-
Circulation. 1977; 56:159-72. nary sequestration in conjunction with bronchial isomerism.
25. Van Praagh R, Van Praagh S. Atrial isomerism in the heterotaxy Thorax. 1983; 38:77-9.
syndromes with asplenia, or polysplenia, or normally formed 42. Cho YH, Jin SJ, Yoon YW, et al. A case of noncompaction of the
spleen: an erroneous concept. Am J Cardiol. 1990; 66:1504. ventricular myocardium combined with situs ambiguous with
26. Rubino M, Van Praagh S, Kadoba K, et al. Venoarterial polysplenia. Yonsei Med J. 2007 December 31; 48(6): 1052-5.
connections in visceral heterotaxy. J Thorac Cardiovasc Surg. 43. Bush A. Left bronchial isomerism, normal atrial arrangement
1996; 111:1107-9. and bronchomalacia mimicking asthma: a new syndrome?
27. Rubino M, Van Praagh S, Kadoba K, et al. Systemic and European Respiratory Journal. August 1999; 14(2):475-7.
pulmonary venous connections in visceral heterotaxy with 44. Van Mierop LHS, Eisen S, Schiebler GL. The radiographic
asplenia: Diagnostic and surgical considerations based on appearance of the tracheobronchial tree as an indicator of
seventy-two autopsied cases. Thorac Cardiovasc Surg. 1995; visceral situs. American Journal of Cardiology. October 1970;
110:641-50. 26(4):432-5.
28. Kearney D, Titus JL. Cardiovascular anatomy, Chapter 4; The 45. Partridge JB, Scott O, Deverall PB, et al. Visualization
science and practice of ped. cardiology, second edition, editors: and measurement of the main bronchi by tomography as an
objective indicator of thoracic situs in congenital heart disease.
Garson A Jr, Bricker JT, Fisher DJ, Neish SR, publishers:
Circulation. 1975; 51:188-96.
Wiliam and Wilkins, 1998; 1:127-55.
46. Henry Gray (1821-1865). Anatomy of the Human Body (online
29. Mc Artney FJ, Zuberbuhler JR, Anderson RH. Morphological
version). 1918. Henry Gray (1821-1865). Anatomy of the
considerations pertaining to recognition of atrial isomerism.
Human Body. 1918. http://is1.mum.edu/vedicreserve/bartleby/
Consequences for sequential chamber localization. Br Heart J.
more_about_charaka.pdf.
1980; 44(6):657-67.
47. Louise Calder A. Thoracic situs as an indicator of atrial
30. Macartney FJ, Shinebourne EA, Anderson RH. Connexions,
appendage morphology: a postmortem study of 306 specimens
relations, discordance and distorsions. British Heart Journal.
with situs solitus in 250 and heterotaxy in 56 cases. Pediatr
1976; 38(4):323-6.
Cardiol. 2011 May 26.
31. Umura H, Ho SY, Devine WA, et al. Atrial appendages and
48. Osman Ratib, Joseph K. Perloff, John S Child. Unique discord-
venoatrial connections in hearts from patients with visceral ance thoracic situs solitus with left isomerism. Circulation.
heterotaxy. Ann Thorac Surg. 1995; 60:561-9 (spleen). 2004; 109:2252-3.
32. Lucas RV, Krabill KA. Anomalous venous connections, 49. Fulcher AS, Turner MA. Abdominal manifestations of situs
pulmonary and systemic. In: Adams FH, Emmanouilides GC, anomalies in adults. Radiographics. 2002; 22:1439-56.
Riemenschneider TA (Eds). Moss’ Heart Disease in Infants, 50. Ticho BS, Goldestein AS. Extracardiac anomalies in the
Children, and Adolescents. Baltimore:Williams and Wilkins. heterotaxy syndromes with focus on anomalies of midline-
1989.pp.580-617. associated structures. American Journal of Cardiology. 15
33. Neill CA. Development of the pulmonary veins. With reference March 2000; 85(6):729-34.
to the embryology of anomalies of pulmonary venous return. 51. Rose V, Izukawa T, Moes CA. Syndromes of asplenia and
Pediatrics. 1956; 18:880-7. polysplenia, a review of cardiac and non-cardiac malformations
34. Van Praagh S, Carrera M, Sanders S, et al. Partial or total direct in 60 cases with special reference to diagnosis and prognosis.
pulmonary venous drainage to right atrium due to malposition BR Heart J. 1975; 37:840-52.
of septum primum: anatomic and echocardiographic findings 52. Gilljam T, McCrindle BW, Smallhorn JF, et al. Outcomes of left
and surgical treatment: a study based on 36 cases. Chest. 1995; atrial isomerism over a 28-year period at a single institution, J
107:1488-98. Am Coll Cardiol. 2000; 36:908-91.
35. Colvin EV. Cardiac embryology, Chapter 3, the science and 53. Ruttenburg HD, Neufeld HN, Lucan RV, et al. Syndrome
practice of ped. cardiology, second edition, editors: Garson A congenital heart disease with asplenia: distinction from other
Jr, Bricker JT, Fisher DJ, Neish SR, publishers: Wiliam and forms from other forms of cyanotic cardiac disease. Am J
Wilkins, 1998.p.1. Cardiol. 1964; 14:587-406.
36. Hashmi A, Abu-Sulaiman R, McCrindle BW, et al. Management 54. Peoples WM, Moller JH, Edwards JE. Polysplenia: a review of
and outcomes of right atrial isomerism: a 26-year experience. J 146 cases. Pediatr Cardiol. 1983; 4:129-37.
Am Coll Cardiol. 1998. 55. Snyder WH Jr, Chaffin L. Embryology and pathology of the
37. Van Praagh S, Geva T, Friedberg DZ, et al. Aortic outflow intestinal tract: presentation of 40 cases of malrotation. Ann
obstruction in visceral heterotaxy: a study based on twenty Surg. 1954; 140:368-79.
postmortem cases. Am Heart J. 1997 May; 133(5):558-69. 56. Applegate KE, Anderson JM, Klatte EC. Intestinal malrotation
38. Ware AL, Miller DV, Porter CB, et al. Characterization of in children: a problem-solving approach to the upper gastroin-
atrial morphology and sinus node morphology in heterotaxy testinal series. Radiographics. Sept 2006; 26:1485-1500.
syndrome: an autopsy-based study of 41 cases (1950-2008).
163
57. Kapa S, Gleeson FC, Vege SS. Dorsal pancreas agenesis and
Cardiovasc Pathol. 2012 Sep; 21(5):421-7. Epub 2012 Jan 28. polysplenia/heterotaxy syndrome: a novel association with
http://vip.persianss.ir
2 aortic coarctation and a review of the literature. JOP. 2007 Jul
9; 8(4):433-7.
75. Marino BS, Bird GL, Wernovsky G. Diagnosis and management
of the newborn with suspected congenital heart disease. Clin
58. Trinavarat P, Tantiprawan K, Khongphatthanayothin A. Chest Perinatol. 2001; 28:91.
BASIcS
radiographic findings in children with asplenia syndrome. 76. Browning Carmo KA, Barr P, West M, et al. Transporting
Asian Biomedicine. August 2010; 4(4):585-94. newborn infants with suspected duct dependent congenital
59. Wren C, Macartney FJ, Deanfield JE. Cardiac rhythm in atrial heart disease on low-dose prostaglandin E1 without routine
isomerism. Am J Cardiol. 1987; 59:1156-8. mechanical ventilation. Arch Dis Child Fetal Neonatal Ed.
60. Momma K, Takao A, Shibata T. Characteristics and natural 2007; 92(2):F117.
history of abnormal atrial rhythms in left isomerism. Am J 77. Gilljam T, McCrindle BW, Smallhorn JF, et al. Outcomes of left
Cardiol. 1990; 65:231-6. atrial isomerism over a 28-year period at a single institution. J
61. Swaminathan S, Parthiban A. Progressive fetal atrioventricular Am Coll Cardiol. 2000; 36:908-91.
block in heterotaxy syndrome. Cardiology in the Young. 2007; 78. Humes RA, Feldt RH, Porter CJ, et al. The modified fontan
17:432-4. operation for asplenia and polysplenia syndrome. J Thorac
62. Huhta JC, Smallhorn JF, Macartney FJ, et al. Cross-sectional Cardiovasc Surg. 1988; 96:212-8.
echocardiographic diagnosis of systemic venous return. Br 79. Kaan Kirali, Ahmet Sasmazel, Ilker Mataraci, et al.
Heart J. 1982; 48:388-403. Biventricular repair of right atrial isomerism with complex
63. Lai WW, Geva T, Shirali GS, et al. Writing Committee, New congenital anomalies. Tex Heart Inst J. 2010; 37(2):202-4.
York, New York Guidelines and Standards for Performance 80. Uemura H, Yagihara T, Kawahira Y, et al. Staged unifocalization
of Pediatric Echocardiogram: A Report from the Task and anatomic repair in a patient with right isomerism. Ann
Force of the Pediatric Council of the American Society of Thorac Surg. 2001; 71:2039-41.
Echocardiography; J Am Soc Echocardiogr. 2006; 19:1413-30. 81. Jonas RA. Surgical Management of the Neonate with
http://www.asefiles.org/pediatricechoguidelines.pdf Heterotaxy and Long-term Outcomes of Heterotaxy; World
64. Karadeniz A, Oysu AS, Sahin S. Polysplenia/heterotaxy Journal for Pediatric and Congenital Heart Surgery April 13,
syndrome associated with aortic coarctation and multiple 2011; 2(2):264-27469.
venous anomalies: multidetector computed tomography 82. Hoashi T, Bove EL, Devaney EJ, et al. Outcomes of 1½- or
findings. Vasc Endovascular Surg. July 2010; 44(5):381-4, first 2-ventricle conversion for patients initially treated with single-
published on May 18, 2010. ventricle palliation. J Thorac Cardiovasc Surg. 2011; 141:419-
65. Chen S, Li YW, Wang JK, et al. Usefulness of electron beam 24.
computed tomography in children with heterotaxy syndrome. 83. Burstein DS, Mavroudis C, Michael DP, et al. Pulmonary
American Journal of Cardiology. 15 January 1998; 81(2):188- Arteriovenous Malformations in Heterotaxy Syndrome
94. the Case for Early, Direct Hepatic Vein–to–Azygos Vein
66. Wang JK, Li YW, Chiu IS, et al. Usefulness of magnetic Connection; World Journal for Pediatric and Congenital Heart
resonance imaging in the assessment of venoatrial connections, Surgery. December 30, 2010; 2(1):119-28.
atrial morphology, bronchial situs, and other anomalies in right 84. Koh M, Yagihara T, Uemura H, et al. Biventricular repair for
atrial isomerism. Am J Cardiol. 1994 Oct 1; 74(7):701-4. right atrial isomerism. Ann Thorac Surg. 2006; 81(5):1808-
67. Elliott LP, Cramer GG, Amplatz K. The anomalous relationship 16.
of the inferior vena cava and abdominal aorta as a specific 85. Yildirim SV, Tokel K, Varan B, et al. Clinical investigations
angiographic sign in asplenia. Radiology. 1966; 87:859. over 13 years to establish the nature of the cardiac defects in
68. Donna A Goff, Elizabeth D Blume, Gauvreau K, et al. Clinical patients having abnormalities of lateralization. Cardiol Young.
outcome of fenestrated fontan patients after closure the first 10 2007 Jun; 17(3):275-82.
years. Circulation. October 24, 2000; 102(17):2094-9. 86. Ota N, Fujimoto Y, Murata M, et al. Improving outcomes of
69. Alsoufi B, Alfadley F, Al-Omrani A, et al. Hybrid management the surgical management of right atrial isomerism. Ann Thorac
strategy for percutaneous fontan completion without surgery: Surg. 2012; 93(3):832-9.
early results. Ann Thorac Surg. 2011; 91:566-73. 87. Swisher M, Jonas R, Tian X, et al. Increased postoperative
70. Newman B, Feinstein JA, Cohen RA, et al. Congenital and respiratory complications in patients with congenital heart
extrahepatic portosystemic shunt associated with heterotaxy disease associated with heterotaxy. J Thorac Cardiovasc Surg.
and polysplenia. Pediatr Radiol. 2010; 40:1222-3. 2011; 141:637-44. e383.
71. Cheatham JP. The transcatheter management of the neonate and 88. Lim G, Bacha EA, Marx GR, et al. Biventricular repair in
infant with pulmonary atresia and intact ventricular septum. J patients with heterotaxy syndrome. J Thorac Cardiovasc Surg.
Interven Cardiol. 1998; 11:363. 2009; 137:371-9.
72. Duff DF, McNamara DG. History and Physical Examination of 89. Berg C, Geipel A, Smrcek J, et al. Prenatal diagnosis of
the Cardiovascular System. In: Garson A Jr, Bricker TM, Fisher cardiosplenic syndromes: 10-year experience. Ultrasound Obstet
DJ, Neish SR (Eds). The Science and Practice of Pediatric Gynecol. 2003; 22:451-9.
Cardiology Baltimore Williams and Wilkins. 1998.p.693. 90. Lin AE, Ticho BS, Houde K, et al. Heterotaxy: associated
73. Lees MH. Cyanosis of the newborn infant. Recognition and conditions and hospital-based prevalence in newborns. Genet
clinical evaluation. J Pediatr. 1970; 77:484. Med. 2000 May-Jun; 2(3):157.
74. Jones RW, Baumer JH, Joseph MC. Arterial oxygen tension 91. Lin JH, Chang CI, Wang JK, et al. Intrauterine diagnosis of
and response to oxygen breathing in differential diagnosis heterotaxy syndrome. Am Heart J. 2002 Jun; 143(6):1002-8.
of congenital heart disease in infancy. Arch Dis Child. 1976; 92. Raman R, Al-Ali SY, Poole CA, et al. Isomerism of the right
164
51:667. atrial appendages: clinical, anatomical, and microscopic study
of a long-surviving case with asplenia and ciliary abnormalities.
Clin Anat. 2003 May; 16(3):269-76.
99. Update for guidelines for the prevention and treatment of
infection in patients with an absent or dysfunctional spleen.
10
93. Brandenburg VM, Krueger S, Haage P, et al. Heterotaxy Working Party of the British Committee for Standards in
HeTeRoTAxy SyndRome
syndrome with severe pulmonary hypertension in an adult. Haematology Clinical Haematology Task Force. 2001.
94. Nagel BHP, Williams H, Stewart L, et al. Splenic state in (Accessed Dec 2006, at http://www.bmj.com/cgi/elet-
surviving patients with visceral heterotaxy. Cardiology in the ters/312/7028/430.
Young. 2005; 15:469-73. 100. Price VE, Dutta S, Blanchette VS, et al. The prevention and
95. Waghorn D. Overwhelming infection in asplenic. J Clin Pathol. treatment of bacterial infections in children with asplenia
2001 March; 54(3):214-8. or hyposplenia: Practice considerations at the Hospital for
96. De Porto APN, Lammers JJ, Bennink RJ, et al. Assessment Sick Children, Toronto. Pediatric Blood and Cancer. 2006;
of splenic function. Eur J Clin Microbiol Infect Dis. 2010 46(5):597-603. http://emedicine.medscape.com/article/
December; 29(12):1465-73. 885226-treatment.
97. Styrt B. Infection associated with asplenia: risks, mechanisms, 101. Langley JM, Dodds L, Fell D, et al. Pneumococcal and
and prevention. Am J Med. 1990; 88(5):33N-42N. influenza immunization in asplenic persons: a retrospective
98. Davidson RN, Wall RA. Prevention and management of population-based cohort study 1990-2002. BMC Infect Dis.
infections in patients without a spleen. Clin Microbiol Infect. 2010; 10:219.
2001; 7(12):657-60.
165
http://vip.persianss.ir
C hapter
Non-shunt lesions Obstructive lesions Aortic stenosis, subaortic obstruction, supra-aortic obstruction
Pulmonary stenosis, infundibular stenosis
Coarctation of aorta/interruption of aorta
Left ventricular inlet obstructions (parachute mitral stenosis,
supramitral ring, cor triatriatum)
Table 2
Table 3
Nadas criteria for the diagnosis of congenital heart diseases Causes of congestive heart failure in acyanotic congenital heart
diseases according to age
Major criteria Minor criteria
1. Systolic murmur of grade Systolic murmur grade 2/6 Age Causes
3–4/6 1st day of life Large arteriovenous fistula, congenital
2. Diastolic murmur Abnormal second heart sound severe pulmonary regurgitation (volume
overload of right ventricle), premature infant
3. Congestive heart failure Abnormal chest X-ray having large PDA, pinpoint aortic stenosis
4. Cyanosis ECG abnormalities with hydrops fetalis
Abnormal BP 1st week of life Coarctation of aorta, critical aortic stenosis,
critical pulmonary stenosis
Presence of one major and two minor criteria are essential for diagnosis of
congenital heart diseases 1st month of life Coarctation of aorta with large PDA, large
VSD, large PDA, AV septal defect
6 month of life Any of the above conditions, VSD with PDA
suspected cardiovascular disorders. But, in our country due to or without PDA, anomalous origin of the
low literacy rate, eliciting proper history from the parents or left coronary artery from pulmonary artery,
relatives can be difficult for the clinicians. aortoventricular tunnels
1 year of life Large VSD, AV septal defect
Presenting Complaints AV = Atrioventricular; PDA = Patent ductus arteriosus; VSD =
Ventricular septal defect
The magnitude of the shunt or the severity of the obstruction
determines the clinical presentation and symptoms. Suspicion
of a congenital heart defect should be raised by the presence 5. Recurrent respiratory infections
of: 6. Growth impairment in the infant
1. Feeding difficulties 7. Exercise intolerance
2. Tachypnea 8. Easy fatigability or murmur in the older child.
3. Sweating The age of presentation with heart failure also gives a clue
4. Subcostal recession regarding the type of acyanotic CHD (Table 3). 167
http://vip.persianss.ir
2 Symptoms to thrive is defined as weight < 3rd percentile for age. Usually,
the rate of weight gain is more delayed than that of height
Feeding Difficulties gain. It is probably related to the inadequate caloric intake due
Basics
Table 4
Pathophysiology of common symptoms
Symptoms Pathophysiology
Tachypnea ↑ PBF will cause engorged vasculature resulting in interstitial edema. This is due to the
transudation of fluid under increased pressure across the capillary walls, which is faster
than the lymphatic clearance). This also acts as a barrier for proper gaseous exchange,
rendering the process less effective. To compensate for this the respiratory rate is ↑ due
to stimulation of the J (juxtacapillary) receptors in the alveolar interstitium, adjacent to the
pulmonary capillaries, due to the interstitial edema.
Dyspnea or shortness of breath Occurs due to pulmonary congestion or interstitial edema from either left-sided cardiac
failure or other conditions raising pulmonary venous pressure or from ↓ oxygen diffusion
and hypoxemia. Left ventricular failure causes ↑ LVEDP and pulmonary venous pressure.
This causes a high back pressure in the pulmonary vessels and transudation of fluid into the
interstitial tissue, making the lungs less compliant. The child has to work harder to breathe.
Chest retractions ↓ tidal volume and pulmonary compliance with ↑ expiratory airway resistance due to ↑
interstitial lung water results in ↑ work of breathing, which is manifested as tachypnea,
intercostal and subcostal chest retractions. Wet and stiff lungs encourage secondary
infection. In very sick infants, grunting and flaring of alae nasae can also be present. ↑ PBF
may also result in compromise of the airways, leading to atelectasis and emphysema.
Feeding difficulties Feeding itself is a form of exercise or effort. Children with respiratory distress and poor CO
due to heart disease cannot feed well as it requires considerable effort to suck resulting in
easy fatigability and failure to thrive. Also, as the feeds are inadequate, they are irritable.
Recurrent respiratory infections As a result of ↑ PBF the engorged pulmonary arteries compress the adjacent bronchi and
bronchioles leading to:
1. Microatelectasis, which leads to stasis of secretions. Atelectasis may also occur,
particularly in the right upper or middle lobe, in these children.
2. There is also goblet cell hyperplasia which causes increased mucus secretion. Both
these cause stagnation of mucus which forms a nidus for infection.
3. Coupled with this, there is the defects in clearance of airway secretions due to
abnormalities of the respiratory mucus or defects in the mucociliary function causing
reduced ciliary movement. This may be due to structural defects of cilia or secondary to
various infections.
4. These children also have decreased immune mechanism and they may be associated
with syndromes, which make them more prone to infections.
5. In addition, increased number of respiratory infections occurs due to blood pooling in the
lungs which is likely to prompt bacterial growth. 169
Contd...
http://vip.persianss.ir
2 Contd...
Symptom Pathophysiology
Basics
Fatigue or exercise intolerance Mainly due to the poor CO and increased energy consumption by an overworked heart.
Poor weight gain or failure to thrive Mainly due to increased caloric demands due to increased work of breathing and overworked
myocardium with increased energy consumption to maintain an adequate CO combined
with poor intake. The child due to poor CO, tires easily during feeding and is unable to take
a full feed and also the rapid respirations diminish the time available for swallowing. There
is also secretion of anorexic hormones that limit the volume of feeds. The child has poor
appetite, frequent respiratory infections and poor absorption of nutrients from the digestive
tract. The poor CO and poor feeding due to shortness of breath and the elevated metabolic
expenditures associated with increased respiratory effort and myocardial work, leads to
decreased nutritional intake and/or increased catabolism.
Syncope May result from impaired response of the autonomic nervous system or from cardiac struc-
tural defects, especially those obstructing blood flow or from cardiac arrhythmias.
CO = Cardiac output; LVEDP = Left ventricular end diastolic pressure; PBF = Pulmonary blood flow.
Table 5
Box 1: Risk factors for CHD
Modified classification of heart failure by Ross
Maternal History
Types Features Diseases
Class I No limitations or symptoms • Diabetes mellitus—VSD/hypertrophic cardiomyopathy,
pulmonary stenosis, PDA, TGA
Class II Mild tachypnea or diaphoresis with feeding in
• Systemic lupus erythematosus—complete heat block
infants
• Phenylketonuria—VSD, ASD, PDA
Dyspnea on exertion in older children
No growth failure Infections/Ingestions/Exposure
Class III Marked tachypnea or diaphoresis with feeds or Infections
exertion • Rubella—PDA, pulmonary artery branch stenosis, congeni-
Prolonged feeding times tal rubella syndrome
Growth failure from congestive heart failure • Mumps—endocardial fibroelastosis
• Coxsackie virus, Cytomegalovirus, herpesvirus (in late
Class IV Symptoms at rest with tachypnea, retractions, pregnancy)—myocarditis
grunting or diaphoresis
Drugs
• Amphetamines—VSD, PDA, ASD, TGA
• Phenytoin (Dilantin)—PS, AS, CoA, PDA
as 10 percent. When a first cousin has a congenital heart • Trimethadione—VSD, PS, TGA, TOF, HLHS
anomaly, the risk of a sibling having one is approximately 2 • Lithium—Ebstein’s anomaly
• Retinoic acid—conotruncal anomalies
percent. With no family history of CHD, if the firstborn has
• Valproic acid—ASD, VSD, AS, CoA, pulmonary atresia with
a congenital heart lesion, the risk of a second child having a intact IVS
congenital heart lesion is 2 to 3 percent, slightly higher than • Progesterone and estrogen—VSD, TOF, TGA
the risk for the general population. Ingestions/Exposure
• Alcohol (fetal alcohol syndrome)—VSD, PDA
Maternal History • Marijuana, cocaine—VSD
• Smoking—PDA, prematurity
A maternal history of acute illness or exposure to drugs
especially in the first trimester or any chronic illness in the AS = Aortic stenosis; ASD = Atrial septal defect; CoA = Coarctation of
aorta; HLHS = Hypoplastic left heart syndrome; IVS = Interventricular
mother may provide an etiological information. The history septum; PDA = Patent ductus arteriosus; PS = Pulmonary stenosis;
should include: TGA = Transposition of great vessels; TOF = Tetralogy of Fallot;
a. Exposure to drugs (lithium, phenytoin, thalidomide) VSD = Ventricular septal defect
b. Alcohol intake
c. TORCH infections especially rubella
d. Maternal diseases like diabetes mellitus, systemic lupus The most important contributory factors for development
170 erythematous, phenylketonuria of CHD are given in Box 1. In most instances, however, no
e. Exposure to radiation. specific contributory factors can be identified.
PHYSICAL EXAMINATION 11
The following are several specific features that should be
General Appearance
A wide spectrum of extracardiac malformations occur in 15-45%
of cases with CHD. Extracardiac malformations can give a clue
towards certain CHD. One should look for physical deformities
like polydactyly, fingerized thumb (Figure 1), which may
indicate atrial septal defect (ASD) or ventricular septal defect
(VSD). Hypertelorism distinctive webbed neck, low set ears,
micrognathia, malocclusion of teeth, with wide spaced nipples A B
are some of the features seen in Noonan’s syndrome (Figure
Figures 3A and B: A. Mongoloid facies in a 1-year-old with Down’s
2A). Short neck or with low hairline is seen in Down syndrome syndrome; B. Palm of a 3-year-old child with Down’s syndrome show-
(Figures 2B). Mongoloid facies with transverse simian crease ing transverse simian crease
on the palm, hypotonic and hyperflexible limbs are also other
features of Down syndrome (Figures 3A and B). Elfin facies
indicate William’s syndrome (Figure 4). Child having moon like
http://vip.persianss.ir
2
Basics
A B
C D
Figures 5A to D: Marfan’s syndrome: A. Steinberg thumb sign; B. Murdoch-Walker wrist sign; C. Arachnodactyly—Abnormally long and
slender fingers on the left in comparison to normal fingers on the right; D. Kyphoscoliosis with deformed ear
http://vip.persianss.ir
2 Blood Pressure Jugular Venous Pressure
Recording blood pressure (BP) is essential, when assessing Jugular venous pressure (JVP) is raised, when the mean right
Basics
the cardiovascular system. It is often difficult to measure exact atrial (RA) pressure increases indicating right-sided heart
blood pressure in the upper and lower limbs in newborns and failure. The JVP is difficult to interpret in newborns and infants
infants, more so when the neonate is a premature one. Blood (due to short neck and tachycardia). But in cases of younger
pressure is taken by different methods at different ages. The children and adolescence, JVP is easily studied. Prominent ‘a’
methods are: (i) Flush method, (ii) Doppler ultrasound wave indicates a forceful atrial contraction present in cases
method and (iii) Oscillometric (Dinamap) method (these of tricuspid atresia, pulmonary stenosis with intact ventricular
are mainly for infants) besides conventional methods like septum, right atrial myxoma and Eisenmenger syndrome due
palpation. to ASD or PDA. In Lutembacher syndrome left atrial ‘a’ wave
Blood pressure cuff of the sphygmomanometer should be is reflected in the JVP. The schematic representation of various
of appropriate size according to the arm circumference. The waves of the normal JVP correlating with heart sounds and
National Heart, Lung, and Blood Institute (NHLBI) has prepared electrocardiogram is illustrated in Figure 6.
a range of blood pressure values based on the age, sex and height
of the children between the ages 3 to 17 years. These values are Oxygen Saturation
based on percentiles. Hypertension is defined as either systolic
and/or diastolic blood pressure ≥ 95th percentile measured on Documentation of systemic oxygen saturation with pulse
three or more separate occasions. The normal range of blood oximetry is generally reserved for patients with active
pressure according to the age given in Table 7. respiratory issues or known cyanotic heart disease.
In all patients suspected of cardiac disease, one should Documentation of oxygen saturation of less than 94 percent
record accurately the BP in both arms and one leg. This helps in the lower extremity would alert the practitioner, either to
in diagnosis of conditions causing obstruction such as CoA, cyanotic CHD or to any condition in which there is right-to-
recognition of conditions with ‘aortic runoff,’ such as PDA, left shunting through the PDA into the descending aorta. This
aortopulmonary window and identification of conditions with differential cyanosis is seen in left heart obstructive lesions
reduced cardiac output. The patient should be in a quiet, resting such as CoA, interrupted aortic arch, hypoplastic left heart
state and appropriate sized BP cuff must be used. The “ideal” syndrome, critical aortic stenosis or pulmonary hypertension
cuff should have a bladder length that is 80 to 100 percent and with PDA.
a width that is at least 40 percent of the arm circumference.
In infants, placing the cuff around the forearm and leg rather Precordial examination
than around the arm and thigh is easier. A 2-inch-wide cuff
can be used for almost all infants.
Inspection
Upper extremity hypertension can be an important first sign
of CoA, but is often missed in children younger than 3 years The precordium is the front of the chest overlying the
if BP is not obtained. The CoA is suspected, when the systolic heart. One should look for abnormal chest shape, visible
pressure is < 20 mm Hg in the legs than in the arms. Pulse pulsations, operation scars and an implanted pacemaker.
pressure (the difference between the systolic and diastolic The left side of the thorax is prominent anteriorly or the
pressures) normally should be approximately one-third of precordial bulge is seen due to the left atrial enlargement,
the systolic BP. A narrow pulse pressure is associated with as in post-tricuspid shunts. The upper sternum may bulge
a low cardiac output or severe aortic stenosis. Pulse pressure in children with a large left-to-right shunt and pulmonary
widens in conditions with an elevated cardiac output (anemia hypertension or with elevated pulmonary venous pressure.
and anxiety) or with abnormal runoff of blood from the aorta As the left atrium is a posterior structure it has to enlarge
during diastole (PDA or aortic insufficiency). anteriorly and hence pushes the compliant sternum and
anterior ribs forward. This may not be evident in the first
Table 7
month of life, but it certainly will be by 3 months of age.
Normal range of blood pressure values In older patients with right ventricular (RV) hypertrophy
secondary to pulmonary hypertension there can be a
Age group Systolic Diastolic
(mm Hg) (mm Hg) prominant precordium. Other types of chest deformities
are pectus carinatum, (Figure 7A) and pectus excavatum
1. Neonates 60–70 20–60
(Figure 7B). Subcostal indrawing is abnormal and usually
2. Infants 87–105 53–65 indicates stiff lungs from either cardiac or pulmonary
3. Toddler 95–105 53–66 causes. If the child has been symptomatic with respiratory
4. Children 97–112 57–71 distress due to heart failure for more than 2 months, bilateral
174 Harrison’s sulci may be seen. This is due to the increased
5. Adolescents 112–128 66–80
11
Palpation
Apex Beat
Several findings may be discovered by palpation, the most
important being the localization of the cardiac apex, which
is an indicator of cardiac size. Obviously, if the apex is in
the right hemithorax, there is dextrocardia. The apex beat
is the point of maximal cardiac impulse. In infants and
children below 4 years, the apex beat is located in the fourth
intercostal space (ICS). Between 4 and 7 years it can be either
in the fourth or fifth ICS and thereafter in the fifth ICS. The
displacement of the apex beat laterally or inferiorly indicates
cardiac enlargement. A hyperdynamic apical impulse is seen
in volume overload conditions like post-tricuspid shunts and a
A B sustained heaving apical impulse is seen in pressure overload
Figures 7A and B: A. Pectus carinatum and B. Pectus excavatum
conditions like in LVOTO.
Thrill
diaphragmatic contractions during respiration, which
produces a sulcus in the lower thorax, with outward flaring A thrill is a palpable vibration caused by turbulent blood
of the inferior ribs. flow and is always pathological. Thrills are best identified
The abnormal location of the apical beat for age indicates by palpation of the precordium with the palmar surfaces
cardiomegaly. The visible pulsations over the precordium or of the metacarpophalangeal and proximal interphalangeal
hyperdynamic precordium is mainly seen in volume overload joints. Thrills are coarse, low-frequency vibrations occurring
conditions like in post-tricuspid shunts. Left parasternal with a loud murmur and are located in the same area, as the
pulsations and lift can be seen in large atrial septal defects maximal intensity of the murmur. Thrills at the lower sternal
and in cases of RV hypertrophy. In patients with PDA, border are more likely to be associated with VSDs than mitral
aortopulmonary window, aortic insufficiency, aortic stenosis or tricuspid regurgitation. Thrills at the right upper sternal
and CoA, suprasternal pulsations can be visible. border (RUSB) or suprasternal notch are most likely to be due
175
http://vip.persianss.ir
2 to severe aortic stenosis. Other less common cause of thrill the young individual S3. Normally, mitral (M1) and aortic
in the suprasternal notch is pulmonary stenosis. Diastolic (A2) heart sounds are louder than and precede tricuspid (T1)
thrills are less common. Parasternal lift or heave is a forceful, and pulmonary (P2) heart sounds. In children, the individual
Basics
outward movement of the left lower parasternal region of the mitral and tricuspid components are usually indistinguishable,
precordium and it indicates RV hypertrophy. so the first heart sound is apparently single. Occasionally, two
components of this sound are heard. A loud S1 can occur with
Percussion increased flow across the AV valves from large left-to-right
shunts, such as ASD, VSD or PDA.
Percussion of the heart can substantiate estimation of cardiac Potain in 1866 recognized splitting of the two components,
size in addition, to that obtained by inspection and palpation. aortic (A2) and pulmonic (P2), of the second heart sound during
It is redundant now. normal inspiration. Splitting of S2 is physiological and normal
on inspiration, when the degree of splitting increases, whereas
Auscultation on expiration it decreases. Shaver et al in 1974 described this
‘Hangout interval’ as a time interval or gap between the arterial
For the auscultation of heart sounds in infants and small pressure curve and the respective pumping chamber pressure
children pediatric-sized bell and diaphragm should be used. curve (right or left ventricle) at the level of incisura. Incisura is
High-pitched murmurs, first and second heart sounds are the notch on the descending limb of the arterial pressure curve,
better heard with the diaphragm; low-pitched murmurs, third which coincides with the pulmonary or aortic valve closure.
and fourth heart sounds are most evident with the bell. The In the highly compliant (low-resistance, high-capacitance)
patient should be examined in a quiet area and in multiple pulmonary vascular bed, the hangout interval may vary from
positions such as supine, left lateral decubitus, upright and 30 to 120 msec contributing significantly to the duration of
leaning forward, as well as during inspiration and expiration. RV ejection. In the left side of the heart, because impedance is
The examiner should auscultate over the listening areas; 2nd much greater, the hangout interval between the aorta and left
RICS, 2nd LICS, 4th LICS and the apex. The carotids and ventricular pressure curve is negligible (less than or equal to 5
chest areas, both front and back, should also be included.The msec). The hangout interval therefore correlates closely with
auscultatory areas are shown in Figure 8. the impedance of the vascular bed into which blood is being
injected. Its duration appears to be inversely related to vascular
Heart Sounds impedance. Leatham in 1964 described the second heart sound
as the “key to the auscultation of the heart”. The S2 is of great
The first and second heart sounds are produced by the valve diagnostic significance and also helps in assessing the severity
closure of the atrioventricular (AV) and semilunar valves of the lesion.
respectively. The normal heart sounds include S1, S2 and in Normal splitting: Some acyanotic CHDs with normal
splitting are small VSD, mild aortic or pulmonic stenosis.
The second heart sound can be split abnormally either as
wide (persistent splitting, with normal respiratory variation)
or fixed split (persistent splitting without respiratory variation)
or paradoxical (reversed) splitting.
Wide splitting: The wide splitting of S2 can occur either due
to conditions prolonging RV ejection and causing a delay in
the pulmonic valve closure with a wide hangout interval or
in conditions with short left ventricular systole causing an
early closure of the aortic valve. Acyanotic CHDs causing
a delay in P2 may occur either due to decreased impedance
of the pulmonary vascular bed (e.g. ASD, partial anomalous
pulmonary venous connection (PAPVC), idiopathic dilatation
of the pulmonary artery) or due to RV pressure overload
lesions (e.g. moderate to severe valvular pulmonic stenosis,
pulmonary hypertension with right heart failure and acute
massive pulmonary embolism). Wide splitting may occur
with an early A2 in patients with decreased resistance to left
ventricular outflow.
Fixed splitting: The fixed splitting of S2 denotes absence of
significant variation of the splitting interval with respiration,
176 such that the separation of A2 and P2 remains unchanged
Figure 8: Standard auscultatory areas during inspiration and expiration.
In ASD the fixed nature of the split is due to approximately valve or deformity of the chest wall or lung. Loud A2 is due 11
equal inspiratory delay of the aortic and pulmonic components, to increased flow, increased pressure and dilatation of the
indicating that the two ventricles share a common venous root of aorta. It can also be appreciated in acyanotic CHDs
http://vip.persianss.ir
2 Ejection Clicks 2. Forward flow through a constricted or irregular orifice or
into a dilated vessel or chamber.
Clicks are classified as ejection or nonejection clicks. The 3. Backward or regurgitant flow through an incompetent
Basics
most common clicks occur in systole and are related to valve, septal defect or patent ductus arteriosus.
abnormalities of the aortic, pulmonic and mitral valves. A combination of these factors is frequent. Before laying
Systolic ejection clicks are abnormal and they mark the a stethoscope on the patient’s precordium, the physician must
transition from the isovolumetric contraction period, to the have a clear concept of what to listen and where to auscultate.
onset of the ventricular ejection. It can be heard shortly after The importance of listening with the child supine cannot
the opening of the semilunar valves and are sharp, high-pitched be over- stressed. Murmurs, which are frequently detected
sounds with a click-like or clicking quality. They are heard in children, may either be innocent (Still’s murmur) or
loudest over their respective valves, except the aortic click pathological and it is important for the clinician to decide the
that is usually well heard at the apex. These sounds have been category.
classified as valvular, originating from deformed aortic and The murmurs are classified by their timing as systolic
pulmonic valves or as vascular, due to the forceful ejection (occurring between the first and second heart sounds), diastolic
of blood into the great vessels. The vascular clicks indicate (between the second sound and the first sound) or continuous
dilatation of either ascending aorta or pulmonary trunk. The (present continuously throughout the cardiac cycle). Continuous
dilatation may be due poststenotic dilation secondary to either murmurs also includes the murmur that begins in systole,
aortic or pulmonary valvular stenosis or from conditions with marches over the second sound and ends in diastole. Other
dilated major arterial trunk, like in Marfan’s syndrome or characteristics of the murmur to be observed are the location,
pulmonary hypertension. The mechanism of valvular click shape (crescendo, decrescendo, diamond, plateau), character
is unknown. It occurs at the point of maximal opening of a or quality (e.g. harsh, soft, blowing, rumbling, vibratory),
stenotic valve suggesting a valvular origin. It may also result radiation (the general rule of thumb is that the sound radiates in
from tensing of the wall of a dilated great vessel in which the direction of the blood flow), intensity or grades, pitch (low,
there are degenerated elastic fibers and the wall is supported medium or high) and variation with maneuvers (inspiration,
by collagen, which is indistensible. standing, squatting).
Ejection clicks in patients with a stenotic semilunar valve The most popular classification of murmur intensity is
occurs more commonly in mild or moderate stenosis and is described by Freeman and Levine. The systolic murmurs are
absent with severe stenosis. The pulmonary ejection click is graded from 1 to 6 and the diastolic murmurs are graded from
unique in that it is loudest during expiration. It is heard best 1 to 4. The intensity of murmur varies with the velocity of
with the diaphragm, in the pulmonary area with the patient blood flow across the area, where murmur is produced. The
sitting. The aortic ejection clicks is widely transmitted and velocity, in turn, is directly related to the pressure that drives
heard best at the cardiac apex or over the left lower thorax the blood across the murmur producing area.
with the patient in a supine position. They do not vary with Grading of Murmurs
respiration. The aortic valvular ejection sound is found Grade 1—so faint that it can be heard only with special
in non-stenotic congenital bicuspid valves. Clicks are not effort.
associated with dysplastic pulmonary valves, which move Grade 2—faint, but can be heard easily.
poorly if at all, or with fixed subvalvular stenosis. Grade 3—moderately loud, but no thrill.
Midsystolic click or non-ejection clicks with or without Grade 4—loud with palpable thrill.
a late systolic murmur is heard at the apex in mitral valve Grade 5—extremely loud and can be heard if only the edge of
prolapse. They are sharp, high-pitched and best heard at the stethoscope is in contact with skin.
cardiac apex. They vary with maneuvers, which alter the left Grade 6— exceptionally loud and can be heard with
ventricular volume. They are louder, when patient is standing stethoscope just removed from skin contact.
or sitting as LV volume is small and softer when patient
reclines or squats, which results in larger LV volume. Age of Presentation of Murmur
http://vip.persianss.ir
2
Basics
Figure 9: Schematic diagram of various murmurs in different acyanotic congenital heart diseases. A2 = Aortic component of second heart sound;
AS = Aortic stenosis; ASD = Atrial septal defect; EC = Ejection click; MR = Mitral regurgitation; MS = Mitral stenosis; P2 = Pulmonary component
of second heart sound; PDA = Patent ductus arteriosus; PH = Pulmonary hypertension; PR = Pulmonary hypertension; PS = Pulmonary
stenosis; S1 = First heart sound; TR = Tricuspid regurgitation; VSD = Ventricular septal defect;
180
associated with pulmonary hypertension and hence signs such
Box 3: Classification of continuous murmurs
11
as a sternal heave (right ventricular hypertrophy) and a louder
P2 may provide additional clues.
http://vip.persianss.ir
2 Table 8
Characteristics of common types of lesions
Basics
• P
ulsatile precordium (active • N
o precordial activity (silent • S
ilent precordium, but forceful RV/LV
precordium with or without precordial precordium) impulse
prominence)
• Cardiomegaly • N
o cardiomegaly • No cardiomegaly
• T
endency for CHF to occur at early • C
HF occurs in late phase • C
HF occurs in very late phase; rarely it
phase mainly during infancy occurs early in severe stenotic lesions
conclusion
where learning begins and where the most judgments
Clinical assessment is a solid foundation for diagnosis and against self are formed. This is also the stage that most
management strategy for cases of CHD. Meticulous history is people give up.
the cornerstone of the diagnosis of some CHDs. 3. Conscious Competence: “I know that I know how to
Auscultation is an art. Never auscultate from the wrong side do this.” This stage of learning is much easier than the
of the bed. One should know, what to hear and where to hear. second stage, but it is still a bit uncomfortable and self-
One should find out the reason, if one does not hear what is conscious.
expected after analyzing the good history, thorough general and 4. Unconscious Competence: “What, you say I did some-
systemic clinical examination. The clinician should not leave thing well?” The final stage of learning a skill is when it
the bedside until systematic analyses has been done of what has become a natural part of us; we do not have to think
one has heard on auscultation. The clinician is the captain of the about it.
ship (patient). If he fails to detect the disease in time by clinical
examination then he will not get the relevant investigations Suggested Reading
done and the patient is denied the proper treatment.
1. Clinical Methods. In: Walker HK, Hall WD, Hurst JW (Eds).
The history, physical and laboratory examinations. 3rd edition.
Stages of Learning Boston: Butterworths; 1990.
2. Libby. Braunwald’s. In: Libby P, Bonow RO, Mann DL, Zipes
1. Unconscious Incompetence: “I do not know that I do
DP (Eds). A Textbook of Cardiovascular Medicine. 8th edition.
not know how to do this.” This is the stage of blissful Elsevier Saunders; 2007.
ignorance before learning begins. 3. Perloff JK, Marelli AJ. Clinical recognition of congenital heart
2. Conscious Incompetence: “I know that I do not know disease. 6th edition. Philadelphia: Saunders, an imprint of
how to do this, yet.” This is the most difficult stage, Elsevier Inc; 2012.
182
C hapter
Clinical Approach to
12 Cyanotic Heart Diseases
Sudhayakumar N
Cyanotic congenital heart disease (CCHD) can be defined as an PBF are usually complex lesions with bidirectional shunt
anatomical congenital cardiovascular birth defect, which results and hyperkinetic PAH; cyanosis in these situations is due
in systemic arterial desaturation due to right-to-left shunt. Review to intercirculatory mixing or because of a transposition like
of literature reveals a reported incidence of congenital heart physiology.
disease (CHD) varying between 1.2 and 17 per thousand live 1. CCHD with low PBF and no PAH
births (probably on an average 8 per 1,000), of which cyanotic i. Tetralogy of Fallot (TOF).
congenital heart disease (CCHD) may contribute to about ii. TOF equivalents (pulmonary stenosis with ventricular
one-fourth.1,2 With recent advances in diagnostic modalities septal defect like pathology).
and improvement in interventional and surgical management, a. Double outlet right ventricle (DORV) + VSD + PS.
the survival and quality of life of children with CCHD have b. D-transposition of great arteries (d-TGA) + VSD +
improved tremendously. Though technology has revolutionized PS.
the diagnostic tools, a clear understanding of pathophysiology c. L-transposition of great arteries (l – TGA) + VSD
along with meticulous clinical examination and analysis of + PS.
simple bedside investigations like 12-lead electrocardiogram d. Tricuspid atresia + VSD + PS.
and chest skiagram can contribute heavily to proper diagnosis e. Single ventricle + PS.
and management of even very complex CCHDs. f. Truncus arteriosus with small pulmonary arteries.
Cyanotic congenital heart disease includes a wide spectrum iii. Pulmonary atresia with intact interventricular septum.
of anatomical and physiological aberrations ranging from a iv. PS with atrial septal defect (ASD).
relatively simple lesion like mild tetralogy of Fallot to very v. Ebstein anomaly of tricuspid valve.
complex problems like hypoplastic left heart syndrome 2. CCHD with low PBF and PAH
(HLHS). Though there are different approaches to classification, Eisenmenger syndrome.
an initial basic approach is based on the pulmonary blood 3. CCHD with high PBF
flow (PBF), as the systemic arterial saturation is primarily i. Intercirculatory mixing (admixture physiology)
determined by the volume of oxygenated blood that comes a. Venous level—total anomalous pulmonary venous
to the systemic circulation from the pulmonary capillaries.3,4 drainage (TAPVD).
Thus, CCHDs can be classified as those with, b. Atrial level—single atrium, tricuspid atresia, HLHS.
1. Reduced pulmonary blood flow (Qp/Qs < 1). c. Ventricular level—single ventricle.
2. Increased pulmonary blood flow (Qp/Qs > 1). d. Arterial level—truncus arteriosus.
3. Near normal pulmonary blood flow. ii. Transposition physiology
Basic abnormality in this group is a very high resistance a. d-TGA.
to PBF either because of pulmonary stenosis or severe b. Taussig-Bing anomaly.
pulmonary arterial hypertension (PAH), so that the ventricles 4. CCHD with near normal PBF
find it easier to empty to the systemic circulation. Hence, i. Pulmonary arteriovenous fistula.
these entities can be subdivided into those with pulmonary ii. Anomalous drainage of vena cava to left atrium (LA).
stenosis (PS) and those with PAH. CCHDs with increased iii. Unroofing of coronary sinus into the LA.
http://vip.persianss.ir
2 CCHD can also be classified in a different approach as characteristically varying degrees of cyanosis depending on
follows: the severity of pulmonary stenosis and history of squatting.
1. TOF physiology. Cyanotic spell is almost diagnostic for this entity. Those with
basics
2. Transposition physiology. increased PBF will have features of heart failure (dyspnea,
3. Admixture physiology. interrupted feeding due to dyspnea, failure to thrive, etc.),
• Pretricuspid—TAPVD, HLHS, tricuspid atresia, single frequent respiratory tract infection and relatively lesser degrees
atrium of cyanosis. Acute pulmonary edema like presentation in the
• Post-tricuspid—single ventricle, truncus arteriosus. neonatal period in a cyanotic baby may indicate obstructed
4. Eisenmenger physiology. TAPVD or HLHS with restrictive interatrial communication.5
5. Ductus dependent physiology. Cyanosis in TOF typically appears a few weeks after birth;
• Ductus-dependent pulmonary circulation, e.g. pulmonary however, as the severity of Fallot increases, the cyanosis can
atresia appear earlier. Cyanosis on day 1 indicates either d-TGA or
• Ductus-dependent systemic circulation, e.g. HLHS. other complex situations. In Ebstein anomaly, a characteristic
6. Near normal physiology, e.g. pulmonary arteriovenous biphasic pattern is described—cyanosis at birth; disappears as
fistula. pulmonary resistance falls and reappears later as right heart
7. Miscellaneous, e.g. Ebstein anomaly, PS + ASD. failure ensues.6
Maternal history is also important; d-TGA may have
Approach to clinical diagnosis of a correlation with maternal diabetes though this has not
Cyanotic congenital heart disease been supported by recent observations. History of maternal
ingestion of teratogens can also be contributory to diagnosis—
Clinical approach to diagnosis of CCHD should aim at maternal consumption of alcohol has been correlated with
delineating the anatomical and physiological abnormalities occurrence of d-TGA, lithium with Ebstein anomaly and sex
and also the rhythm status of the child. Following aspects hormones with d-TGA and TOF.
have to be addressed.
Physical Findings
Physiology
Meticulous physical examination contributes greatly to arrive
• Pulmonary circulation—flow, pressure, resistance at a reasonable clinical diagnosis of the entity. Presence of
• Systemic circulation—oxygen saturation, cardiac output, dysmorphic or syndromic features gives us a clue to the
blood pressure, resistance underlying condition based on the established associations.6,7
• Ventricular function A few examples are given below:
• Venous pressures—systemic/pulmonary • Down syndrome—atrioventricular canal defects (AVCDs)
• Any obstruction to circulation • DiGeorge syndrome8,9—interrupted aortic arch, truncus
• Ductus dependent or not arteriosus, TOF
• Any compensatory mechanisms. • Laurence-Moon-Biedl syndrome—TOF
• Ellis Van Crevald—Common atrium
Anatomy • Alagille syndrome—TOF
• Velocardiofacial syndrome—conotruncal anomalies
• Visceral and cardiac situs • CHARGE syndrome—HLHS
• Visceroatrial/atrioventricular/ventriculoarterial connection Extracardiac anomalies are seen with a relatively higher
• Right ventricular/left ventricular/biventricular pattern frequency in certain CCHDs—48 percent in truncus arteriosus,
• Great artery relation—normal/transposed/malposed 30 percent in TOF, 20 percent in tricuspid atresia, 15 to 30
• Status of inflow tract and outflow tract of the ventricles percent in HLHS; but less frequent with d-TGA (< 10%).10
• Venous connection—pulmonary and systemic Differential cyanosis is diagnostic for Eisenmenger patent
• Coronary anatomy ductus arteriosus, whereas reversed differential cyanosis occurs
• Collaterals. in d-TGA with ductus and preductal coarctation or PAH.11
Symptomatology contributes to the assessment of physiology
and physical findings guide to anatomical status; radiology and Pulse, Blood Pressure and Jugular
electrocardiogram add to this. Venous pulse
http://vip.persianss.ir
2
basics
Figure 1: Electrocardiogram showing very tall or Himalayan P wave suggestive of right atrial enlargement,
polyphasic splintered QRS in chest leads. Suggestive of Ebstein anomaly
Figure 2: Electrocardiogram in a 5-years-old child with tricuspid atresia with normally related great arteries with left superior axis,
diminished right ventricular forces, left ventricular enlargement with T wave changes
186
hypertrophy or biventricular hypertrophy. Prominent left position of aortic arch can also be determined (Figures 3 to 12
ventricular forces and left atrial overload indicates enhanced 7). Many times, the radiology picture could be diagnostic
PBF. Paucity of right ventricular forces is a clue for tricuspid as in supracardiac TAPVC (snowman appearance), TOF
Figure 3: Classical lifted up right ventricular (RV) apex (coeur en Figure 5: Cardiomegaly, huge right atrium and reduced pulmonary
sabot), concave pulmonary bay, pulmonary oligemia and right aortic vascularity of Ebstein anomaly (box-shaped heart)
arch in tetralogy of Fallot
Figure 4: Cardiomegaly, increased pulmonary vascularity and narrow Figure 6: Classical figure of 8 appearance of total anomalous 187
vascular pedicle (absent visible main pulmonary artery) in d-TGA (egg pulmonary venous connection
on side appearance)
http://vip.persianss.ir
2
basics
Figure 7: Dilated right atrium (RA) and central pulmonary arteries and increased pulmonary vascularity in a cyanotic child,
suggestive of common atrium. MPA = Main pulmonary artery; RPA = Right pulmonary artery
BV = Biventricular; DORV = Double outlet right ventricle; d-TGA = d-transposition of great arteries; HLHS = Hypoplastic left heart syndrome;
LVD = Left ventricular dominance; PAH = Pulmonary arterial hypertension; PA-IVS = Pulmonary atresia with intact ventricular septum; PAVF =
Pulmonary arteriovenous fistula; PBF = Pulmonary blood flow; RVD = Right ventricular dominance; SA = Single atrium; SV = Single ventricle;
TAPVD = Total anomalous pulmonary venous drainage; TA = Tricuspid atresia; VC to LA = Vena cava to left atrium
hump along the left upper border suggests L-posed aorta. in a neonate suggest the possibility of obstructed TAPVC
Right aortic arch is common with truncus arteriosus (pulmonary edema in neonate occurs in HLHS with
(40%), pulmonary atresia with VSD (30%) and TOF restrictive interatrial communication also).
(20–25%).14,15 A higher incidence of left superior vena Clinically, normal heart with normal ECG and chest X-ray
cava has been observed in AVCDs (19%), mitral atresia occur with pulmonary arteriovenous fistula, anomalous vena
(17%), TOF (10%) and truncus arteriosus (9%). Near caval connection to left atrium and unroofed coronay sinus in
188 normal cardiac silhouette with pulmonary edema pattern left atrium.
The overall flow chart for clinical approach to CCHD is 6. Schiebler GL, Adams P Jr, Anderson RC, et al. Clinical
study of 23 cases of Ebstein’s anomaly of the tricuspid valve.
12
illustrated in Flow chart 1.
Circulation. 1959;19:165-87.
189
http://vip.persianss.ir
C hapter
Role of Radiography in
13 Congenital Heart Diseases
side and the left atrium (LA), stomach gas bubble, spleen and
bilobed left lung are on other side. The position of the stomach
gas bubble helps in identifying the visceroatrial situs.
Bronchial Pattern
The bronchial pattern is important in isomerism
(Figure 3). CXR image gives valuable clues to the diagnosis,
as shown in Figures 4 and 5.
i. Tracheal bifurcation is best seen in an oblique view. 191
figure 5: CXR image in right lateral view shows how
ii. Right bronchus is short, wide and straight. to identify the normal structures
http://vip.persianss.ir
2
BasiCs
Bony Cage
All the CXR should be carefully observed systematically
for skeletal abnormalities from the cervical spine, scapula,
clavicle, thoracic spine and ribs in both frontal and lateral
view (Figure 5). In the bony cage one should look for scoliosis
(Figures 6 and 7) in posteroanterior (PA) view and for kyphosis
in lateral film. The incidence of scoliosis in acyanotic CHD
is 20 percent and in cyanotic CHD it is 66 percent. As the
skeletal deformity can pose problems during surgery, chest
X-ray is extremely useful in detecting the problems in the
bony cage. Rare conditions like hemivertebrae can be easily figure 8: CXR image with correct centering. There is equal distance
detected by simple X-ray. The children with Down syndrome between the medical end of clavicle and midline
often have only 11 pairs of ribs. Premature fusion of sternal
segment is usual in cyanotic CHD. Bilateral rib notching is
seen in coarctation of aorta (COA) and unilateral rib notching be checked before reading it. The centering is checked by
is seen in subclavian pulmonary artery anastomosis as in clavicular symmetry. There should be equal distance between
Blalock-Taussig shunt. the medial end of the clavicle and midline (Figure 8). If the
distance between medial end of the clavicle and center line
Is there significant Rotation? is unequal then centering is not correct (Figure 9). If the
centering is not correct then the interpretation can go wrong
Rotation means that the baby was not positioned flat on the due to rotation. Rotation can make the lungs look asymmetrical
X-ray film and one plane of the chest is rotated in comparison and it can change the orientation of the cardiac silhouette. If
192 to the plane of the film. The centering of the CXR has to there is significant rotation, the side, which has been lifted
13
may appear narrower and more dense (white) and the cardiac
silhouette appears more in the opposite lung field.
Cardiothoracic Ratio
Before commenting on cardiomegaly the cardiothoracic
ratio (CTR) must be measured meticulously (Figure 10).
The CTR is equal to the transverse cardiac diameter (TCD)
divided by the transthoracic diameter (TTD) measured at the
inner border of the 9th rib (CTR = TCD/TTD) as shown in
Figure 10. Irrespective of CTR an increase of > 2 cm of TCD
is significant if previous CXR is available. The normal values
of CTR ratio in an adult is 0.41 to 0.5. The upper limit of
normal CTR ratio in infants is 0.55 and 0.60 in neonates.
A TCD of greater than 15 cm is significant irrespective
of normal CTR. An expiratory roentgenogram can lead to
pseudocardiomegaly and a prominent aorta. Epicardial fat in
the cardiophrenic angle can mimic as cardiomegaly as shown
in Figure 11. figure 11: CXR image in a patient epicardial fat in cardiophrenic
angle mimicking cardiomegaly
thymic shadow
(Figure 12A). The right lobe of the thymus can insinuate
The thymic shadow is usually prominent in the first few years into the minor fissure, causing a ‘sail’ sign (Figure 12B). The
of life. Thymic shadow should not be mistaken for mediastinal awareness of various apperances of thymus on CXR can bail
widening. The shadow of the thymus lies anteriorly in one out of a situation wherein thymus mimics a pericardial
relationship to the heart and great vessels. The relative size mass on echocardiography.
of the thymus increases with expiration and decreases with
inspiration. The thymus decreases in size during periods Is the X-ray underexposed or overexposed?
of stress, such as during sepsis. Because the thymus is a
soft organ, its lateral margin can have indentations caused A properly penetrated chest radiograph is one, in which the
due to the overlying costal cartilages, causing a ‘wave’ sign intervertebral bodies can be seen. Normally only the first four 193
http://vip.persianss.ir
2
BasiCs
a B
figures 12a and B: A. CXR image shows the ribs causing indentation on the soft thymus, causing ‘wave’
sign (arrows); B. Right lobe of the thymus can insinuate into the minor fissure, causing ‘sail’ sign (arrow)
vertebral bodies are visible. In overpenetrated or overexposed iii. Pulmonary venous hypertension (PVH) (ground glass
CXR, the vertebral bodies are visible clearly through the appearance).
cardiac shadow. In underpenetrated or underexposed film iv. Pulmonary edema (bat-wing appearance).
the vertebral bodies are not visible at all. An underpenetrated
chest CXR does not differentiate the vertebral bodies from Oligemia
the intervertebral spaces. An overpenetrated film shows the
intervertebral spaces very distinctly. An overpenetrated CXR In oligemia, vascular shadows are reduced. They are not seen
will be darker and the subtleties will be harder to see. An even in the intermediate lung zones. Main pulmonary artery
underpenetrated CXR will emphasize normal lung and make (MPA), left pulmonary artery (LPA) and right descending
it appear as if there are infiltrates. Hence it is important to pulmonary artery (RDPA) are of small size (normally RDPA
know whether the CXR is overexposed or underexposed. is of the same size as the right lower lobe bronchus). Oligemia
Overexposure causes the image to be dark. Under these occurs in critical pulmonary stenosis (PS) and in tetralogy
circumstances, the thoracic spine, mediastinal structures, of Fallot (TOF). In pulmonary valvular stenosis along with
retrocardiac areas, nasogastric and endotracheal tubes are oligemia there is poststenotic dilation of the MPA and the
well seen, but small nodules and the fine structures in the lung right ventricle (RV) and RA are enlarged (Figure 13A). In
cannot be seen. However, the widespread availabilty of digital TOF pulmonary bay is empty (MPA is small) and severe RVH
imaging (computed radiography, direct digital radiography) is seen without RA enlargement (as RV pumps into the over-
has reduced the importance of ‘optimal’ exposure as images riding aorta and the pressure is not transmitted to RA). Nearly
can be manipulted on viewing monitors. 25 percent of TOF can have right sided aortic arch (Figure
13B). The left or right aortic arch can be made out by the
Degree of Inspiration ipsilateral indentation of the trachea.
figure 14: CXR image of a 12-year-old boy with large ventricular septal figure 15: Fluroscopic image of 4 months infant tetralogy of Fallot
defect and atrial septal defect with pulmonary arterial hypertension, with absent left pulmonary artery, shows oligemia in right lung and
shows right atrium, right ventricle, main pulmonary artery dilated with absent vascular markings in left lung
plethora
Occasionally there can be unilateral plethora as in BT there is equalization of the vascularity. When there is severe
shunt and in unilateral major aortopulmonary collateral artery obstruction to the pulmonary veins, the CXR shows ground
(MAPCA). Asymmetry in lung vascularity can also occur glass appearance (Figure 16A). The ground glass appearance
after Glenn surgery and in pulmonary artery branch stenosis due to pulmonary venous hypertension is an important feature
or absent right pulmonary artery (RPA) or LPA (Figure 15). and should be distinguished from hyaline membrane disease.
The normal pulmonary capillary wedge pressure (PCWP) is
Pulmonary Venous Hypertension < 12 mm Hg. Larry Elliot has graded PVH into four stages.
In stage I PVH, the PCWP is between 13 to 17 mm Hg. The
Normally the upper lobe veins are less prominent than the pulmonary veins in the upper lobe are more prominent than 195
lower lobe veins. In PVH or postcapillary hypertension, that in the lower lobe. This is cephalization of the veins and
http://vip.persianss.ir
2
BasiCs
a B
figures 16a and B: A. CXR image of a 2-month-old infant with obstructed infradiaphragmatic total anomalous pulmonary venous connection;
B. CXR of a 50-year-old lady with large atrial septal defect with pulmonary hypertension shows bat-wing appearance
http://vip.persianss.ir
2
BasiCs
a B
figures 19a and B: A. CXR image of Tetralogy of Fallot (TOF) with boot shaped heart with a empty pulmonary bay
with reticular pattern due to collaterals; B. TOF with absent pulmonary valve with dilated pulmonary artery
figure 20: CXR image shows narrow pedicle with egg on string
appearance in a 8-year-old with transposition of great arteries
a B
figures 24a and B: CXR image showing 3 sign and rib notching: A. Chest X-ray in coarctation of aorta (COA) shows concentric left
ventricular hypertrophy with figure-of-3 sign; B. Rib notching is seen in the X-ray of 16-year-old boy of COA with collaterals
the site of coarctation, indentation of the site and dilatation which are diagnostic, e.g. in cases with congenital corrected
of the aorta distal to the site (Figure 24A). transposition of great arteries (CTGV), the malposed ascending
7. Rib notching: It is seen in the lower margin of the third aorta produces a long convexity on the left upper mediastinal
to eighth ribs (Figure 24B) in aortic coarctation due to the contour and cardiomegaly with increased pulmonary vascular
enlarged, tortuous intercostal arteries supplying blood to markings secondary to a ventricular septal defect (Figure 25).
the descending aorta. The notching is not usually seen in The right pulmonary artery appears to have a high take off
children younger than 5 years. because of an absent aortic shadow and is also quite prominent
Apart from specific signs in some condition there are other indicating ventricular inversion. Also in tricuspid atresia, 199
conditions which have characteristic features on radiography, CXR shows a mildy enlarged LV with a gap between RA and
http://vip.persianss.ir
2
BasiCs
figure 25: CXR image of corrected transposition of great arteries. figure 27: CXR image of 32-year-old patient with large patent ductus
The ascending aorta producing a long convexity on the left upper arteriosus with severe pulmonary hypertension shows dilated right
mediastinal contour pulmonary artery and left pulmonary artery with peripheral pruning
Cardiophrenic angles
The cardiophrenic (CP) angle is obliterated in pericardial
effusion (Figure 33). It is obtuse and helps to distinguish from
cardiomegaly, in which the CP angle remains acute, however
great the enlargement is. In patients of CHD with congestive
figure 29: CXR image shows aneurysmally dilated pulmonary artery
with normal cardia and lung field of 18-year-old girl with idiopathic heart failure along with the cardiomegaly the pleural effusion
dilatation of pulmonary artery can be detected on CXR as the costophrenic angle is obliterated.
a B
figures 30a and B: A. CXR image of a patient with pulmonary embolism shows the abrupt tapering and termination of a pulmonary vessels
(horizontal arrow) and hyperlucency (vertical arrows); B. CXR image of a patient with pulmonary infarction with peripheral wedge-shaped area
of opacification with apex towards the hilum
a B 201
figures 31a and B: A. Fluoroscopic image showing atrial septal occluder in situ; B. Fluoroscopic image illustrating in situ ASD device
and a VSD device, in an apical position, deployed simultaneously in 12 years old boy
http://vip.persianss.ir
2
BasiCs
a B
figures 32a and B: A. Fluoroscopic image illustrates the patent ductus arteriosis (PDA) device in situ; B. Fluoroscopic image
of the abdomen shows the PDA device embolized in aorta
figure 33: X-ray film shows the cardiomegaly with obtuse cardiophrenic angle, indicating the presence of pericardial effusion
http://vip.persianss.ir
2
Basics
Figure 1: Confluent pulmonary arteries in tetralogy of Fallot. Figure 2: Oblique coronal maximum intensity projection (MIP)
LPA = Left pulmonary artery; PA = Pulmonary artery; reformat demonstrating coarctation of aorta (CoA).
RPA = Right pulmonary artery AAo = Ascending aorta; DAo = Descending aorta
cardiac surgeons consider it as the most useful investigation tracheal anomalies including tracheal bronchus, complete
for surgical planning. tracheal ring and localized tracheomalacia. CT scan and
3. Tetralogy of Fallot with absent pulmonary valve: CT also digital 3D reconstruction of the CT images can give an
plays an vital role in patients diagnosed as TOF with absent excellent recreation of the precise anatomy of this complex
pulmonary valve who are symptomatic not only because lesion and is the investigation of choice.6
of the cardiac problem, but also because of the inherent 8. Total anomalous pulmonary venous connection (TAPVC)
abnormalities in the lung parenchyma. Determining the PA (Figure 3): Although echocardiography can confidently
anatomy and its contribution to symptoms is of immense diagnose the condition in the vast majority, CT evaluation
importance in deciding the surgical management. Apart gives excellent anatomical data regarding the pulmonary
from defining the amount of bronchial compression, it also veins and should be considered in case of any doubt or
localizes areas of atelectasis or emphysema. when the echocardiographic data does not correlate with
4. Interrupted aortic arch (IAA): IAA represents a separation the clinical condition.7
between ascending and descending aorta. Evaluation of 9. Postoperative situations: An important and established
the distance between the proximal and distal segments, the role of CT in the follow-up of managed CHD is evaluation
size of the patent ductus arteriosus (PDA), the narrowest for successful surgical outcome and recognition of a
dimension of the left ventricular outflow tract and other variety of complications. CT angiography (CTA) can
cardiac structural abnormalities are important for surgical assess surgical conduits and intravascular stent patency,
planning. CT scan and digital 3D reconstruction of the CT wherein lack of central opacification in these structures
images can recreate the entire anatomy for the surgeon and suggests the presence of thrombosis that can have serious
simplify the surgical planning. clinical implications. CTA can also evaluate right ventricle
5. Coarctation of aorta (CoA) (Figure 2): CT scan can give an to pulmonary artery and modified Blalock-Taussig shunt
excellent delineation of the lesion to aid the management patency and stenosis. Similarly, CT can also assess
planning.4 patients previously treated with a surgical cavopulmonary
6. Aortopulmonary window (APW): Echocardiography may anastomosis, such as bidirectional Glenn shunt and Fontan
fail to pick up this lesion due to artificial dropouts and rapid procedures, where CT can establish pathway patency and
development of pulmonary hypertension. A great degree exclude abnormal pathway narrowing. Filling defects
of clinical suspicion needs to be exercised for the proper within the pathway suggest the presence of thrombus.
diagnosis. The role of helical CT has been well established
in the diagnosis of this condition.5 Disadvantages of Computed Tomography
7. Pulmonary artery sling: In this lesion, an aberrant left
204 pulmonary artery arises from the proximal right pulmonary CT has its inherent disadvantages, including the inevitable
artery, courses between the trachea and esophagus and radiation exposure and risks related to use of iodinated
extends to the left hilum. This may be associated with contrast material. Also, CT lacks in its ability at demonstration
Magnetic Resonance Imaging Sequences 14
and Techniques
http://vip.persianss.ir
2 specialized software, regions of interest around a vessel are
defined and the flow rate is automatically calculated.13
Clinically, VEC MRI can be used to quantify cardiac
Basics
207
Figures 7A and B: A. Contrast enhanced MRA demonstrating anomalous origin of left coronary artery from left pulmonary
artery (ALCAPA); B. Volume rendered image of CT angiogram in ALCAPA illustrates left main coronary (LMC) artery arising
from main pulmonary artery (MPA). LAD = Left anterior descending coronary artery; LCX = Left circumflex coronary artery
http://vip.persianss.ir
2 detection of collateral vessels that bypass the coarctation site,
assessment of left ventricular mass, dimensions and function
and detection of any associated lesions.17
Basics
Fontan Circulation
Fontan circulation population subset is at risk for complications
such as systemic ventricular dysfunction, thromboembolism,
dilation of the systemic venous atrium, obstruction of the
Fontan pathways, pulmonary artery stenosis, compression
of the pulmonary veins, atrioventricular valve regurgitation
and arrhythmias. Prompt detection of these complications is
therefore an important element of managing these patients.
Several reports have utilized MRI as an investigational tool
to study blood flow dynamics within the Fontan pathways
and to delineate the distribution of inferior and superior
caval flow to each lung. Myocardial tagging has proved an
Figure 8: Multiplanar true FISP axial image showing large aneurysm important investigational tool in the evaluation of myocardial
of the right ventricular outflow tract (RVOT) in a patient with post- mechanics in patients with a functional single ventricle and
tetralogy of Fallot repair Fontan circulation, demonstrating asynchrony and impaired
regional wall motion.18,19
follow-up of TOF, the patients often have residual anatomic The clinical utility of MRI in patients with the Fontan
and hemodynamic abnormalities such as chronic pulmonary circulation increases as the acoustic windows become more
regurgitation, residual ventricular septal defect, right restricted with growing years. The MRI examination in patients
ventricular volume overload and dysfunction, right ventricular with the Fontan circulation can assess the pathways from the
outflow tract obstruction, branch pulmonary artery stenosis, systemic veins to the pulmonary arteries for obstruction and
residual aortopulmonary collaterals and others. for a thrombus detection of Fontan baffle fenestration or leaks,
The goals of the MRI examination after TOF repair evaluation of the pulmonary veins for compression, systemic
include quantitative assessment of left and right ventricular ventricular volumes, mass and pump function, imaging of the
volumes, mass, stroke volumes and ejection fraction, imaging systemic ventricular outflow tract for obstruction, quantitative
the anatomy of the right ventricular outflow tract (Figure 8), assessment of the atrioventricular and semilunar valve(s) for
PA’s, aorta and aortopulmonary collaterals and to quantify regurgitation, the aorta for obstruction or an aneurysm and for
pulmonary regurgitation, tricuspid regurgitation, cardiac aortopulmonary, systemic venous or systemic to pulmonary
output and pulmonary to systemic flow.16 venous collateral vessels.19
http://vip.persianss.ir
2 15. Masui T, Katayama M, Kobayashi S, et al. Gadolinium
enhanced MR angiography in the evaluation of congenital
comparison between contrast-enhanced MR angiography and
fast spin-echo MRI. Eur Radiol. 2000;10:1847-54.
cardiovascular disease pre and postoperative states in 18. Mayer JE Jr. Late outcome after the Fontan procedure. Semin
Basics
infants and children. J Magn Reson Imaging. 2000;12: Thorac Cardiovasc Surg; Pediatr Cardiol Surg Annu. 1998;1:
1034-42. 5-8.
16. Helbing WA, de Roos A. Clinical applications of cardiac 19. Balling G, Vogt M, Kaemmerer H, et al. Intracardiac thrombus
magnetic resonance imaging after repair of tetralogy of Fallot. formation after the Fontan operation.
Pediatr Cardiol. 2000;21:70-9. 20. Holmqvist C, Hochbergs P, Bjorkhem G, et al. Preoperative
17. Bogaert J, Kuzo R, Dymarkowski S, et al. Follow-up of patients evaluation with MR in tetralogy of Fallot and pulmonary atresia
with previous treatment for coarctation of the thoracic aorta: with ventricular septal defect. Acta Radiologica. 2001;42:63-9.
210
Sec t i on
http://vip.persianss.ir
C hapter
INTRODUCTION posterior veins join before entering the sinus horn and form
the short common cardinal veins. During the fourth week,
The abnormalities of position and connection of the major the cardinal veins form a symmetrical system.
systemic venous channels draining to the heart are mostly Formation of the vena caval system is characterized by the
rare incidental findings with not much of hemodynamic appearance of anastomosis between the left and right sides in
significance, when visceroatrial situs is lateralized. In contrast, such a manner that the blood from the left side is channeled
the incidence of systemic venous anomalies in patients with to the right side (Figure 2). The anastomosis between the
heterotaxy syndrome exceeds 90 percent.1 However, even anterior cardinal veins develops into the left brachiocephalic
when not hemodynamically significant, they may complicate vein (Figures 2 and 3).
interventional procedures and cause arrhythmias. In some Most of the blood from the left side of the head and the left
cases it can cause cyanosis, polycythemia, paradoxical upper extremity is then channeled to the right. The terminal
embolism and even stroke. The relevant embryology portion of the left anterior cardinal vein entering into the left
and anatomy with individual anomalies and their clinical brachiocephalic vein is retained as a small vessel, the left
significance is discussed. superior intercostal vein (Figure 4). This vessel receives blood
from the second and third intercostal spaces. The superior
Classification of Systemic Venous Anomalies vena cava is formed by the right common cardinal vein and
the proximal portion of the right anterior cardinal vein.
1. Anomalies of the superior vena cava A left-sided superior vena cava is an abnormality caused
2. Anomalies of the inferior vena cava by the persistence of the left anterior cardinal vein and
3. Anomalies of the ductus venosus obliteration of the common cardinal and proximal part of the
4. Total anomalous systemic venous connection. anterior cardinal veins on the right. In such a case, blood from
http://vip.persianss.ir
3
Subcategory of SVC Anomalies
Defects in Atriovenous and Pulmonary Arteriovenous Connections
http://vip.persianss.ir
3
The highest incidence of bilateral SVCs with a completely
unroofed coronary sinus is seen in patients with visceral
Defects in Atriovenous and Pulmonary Arteriovenous Connections
Clinical Features
The persistent LSVC with unroofed coronary sinus functions
as an interatrial communication. The hemodynamic conse
quences are cyanosis and right to left shunting. There is
systemic arterial desaturation due to mixing of LSVC blood
with pulmonary venous blood in the left atrium. The degree of
desaturation is related to the net right-to-left shunting, which
in turn depends on the proportion of systemic venous blood
that crosses the atrial septum and reaches the pulmonary
circulation. The complications associated with right-to-left
shunting are paradoxical emboli, brain abscess, strokes and
Figure 8: Right heart catheter through right atrium (RA), coronary
sinus (CS) into left superior vena cava (LSVC). Hand injection of
death.
contrast shows LSVC draining to CS
Diagnosis
occlusion proximal to the injection site is diagnostic. The On the chest radiogram the LSVC may appear as a shadow
LSVC can be approached either through the right SVC (when along the left upper border of the mediastinum.
the innominate vein is present) or through the coronary sinus The electrocardiogram is similar to ostium secundum ASD.
(Figure 8). The diagnosis of systemic venous anomalies can However, in patients with visceral heterotaxy, the frontal axis
be reliably established by echocardiography and MRI, making of the P waves may be abnormal reflecting a left sinoatrial
cardiac catheterization unnecessary in most patients. node or an ectopic atrial rhythm.
The echocardiogram is the definitive imaging modality
Treatment with the subcostal or suprasternal window showing the LSVC
draining into the LA (Figures 9A to C).
No treatment is necessary when the LSVC is draining into an Flow mapping with color Doppler is useful in demons
intact coronary sinus. trating the flow from LSVC into the LA. A contrast injection
in the left arm vein demonstrates the appearance of the micro
Bilateral Superior Vena Cava with Unroofed bubbles in the left atrium before they appear in the right
Coronary Sinus atrium. CT angiogram and magnetic resonance imaging
is useful when the echocardiogram does not delineate the
Unroofed coronary sinus has been classified morphologically anatomy clearly (Figure 9D).
into four types by Kirklin and Barratt-Boyes, which are as Cardiac catheterization is diagnostic (Figure 10) and
follows:20 there is also step-down in the oxygen saturation between the
• Type I: Completely unroofed, with LSVC pulmonary veins and the left atrium. Also the LSVC can be
• Type II: Completely unroofed, without LSVC selectively cannulated.
• Type III: Partially unroofed mid portion
• Type IV: Partially unroofed terminal portion. Treatment
Raghib et al21 described eight cases with the following
findings: It is important to assess the size of the left innominate vein
1. Left superior vena cava drains into the left atrium. before any attempts to close the defect. If the LSVC is of small
2. An atrial septal defect is present. The defect lies in the size and the innominate vein is of adequate size, the LSVC
posteroinferior angle of the atrial septum and above the can be ligated and the interatrial communication closed. But
posteromedial commissure of the mitral valve. It is separated in the absence of an adequate sized innominate vein, it is
from the mitral valve by a small amount of septal tissue. prudent to “reroof” the coronary sinus22 which is achieved by
216 3. Coronary sinus is absent. baffling the coronary sinus along the posterior wall of the left
15
C D
Figures 9A to D: A and B. Suprasternal modified view with colour Doppler in a 3 months old with left isomerism. There is absent right superior
vena cava with left superior vena cava (LSVC) draining into the left atrium (LA); C. Pulse wave Doppler on LSVC, confirms the biphasic venous
flow; D. CT angiogram shows LSVC draining into LA
atrium into the right atrium. The LSVC or coronary sinus can
be closed percutaneously with an ASD device.
http://vip.persianss.ir
3
surgery that includes cavopulmonary anastamosis and ortho As against this, reduced shortening of the aortic arch as
topic heart transplantation. It is not required to treat these seen in right aortic arch and high aortic arch may compress
Defects in Atriovenous and Pulmonary Arteriovenous Connections
patients when the physiology is normal. and prevent the further development of the superior transverse
venous plexus. Abnormal development of the pulmonary arte
Right Superior Vena Cava Draining into the Left Atrium ries, either pulmonary atresia or pulmonary stenosis, encou
rages the sparing of the inferior transverse plexus, possibly
The left atrial drainage of the right superior vena cava is a leading to formation of an anomalous course of the innominate
rare anomaly, manifesting as unexplained cyanosis and vein. This would explain frequent association of the retroaortic
clubbing.26 innominate vein with TOF and right aortic arch.29-31
This malformation probably represents a sinus venosus Usually, the retroaortic innominate vein in isolation has no
defect of the SVC type in association with atresia of the right clinical importance. The descending portion of the retroaortic
SVC orifice. There is unroofing of the right upper pulmonary innominate vein may be mistaken for persistent LSVC or
vein and its branches which drain into SVC and its left atrial an ascending vertical vein in a total anomalous pulmonary
orifice becomes the inter atrial communication. The left atrial venous connection on echocardiography.32 The retroaortic
blood can be shunted into the SVC-RA junction or the right segment may be misinterpreted as right pulmonary artery in
SVC blood can enter the left atrium depending on the pressure patients with hypoplastic or atretic central pulmonary arteries,
and the compliance differences between the two atria. or an early branching of right upper lobe pulmonary artery on
Cyanosis is the dominant clinical feature when the echocardiography.33,34
right SVC drains into the left atrium. The risks include In a retrospective analysis of echocardiograms the
polycythemia, systemic emboli, brain abscess, and other incidence of retroaortic innominate vein was found to be 0.55
cerebrovascular complications typically increasing with age. percent amongst children with congenital heart disease. It was
On the echocardiogram the common entrance site of right most commonly associated with tetralogy of Fallot and right
SVC and the right upper pulmonary vein in the roof of the left aortic arch.35
atrium can be demonstrated.27 It is widely considered to be anatomical variant without
Surgery is the treatment of choice where the right SVC clinical ramifications. However, knowing the precise
flow is diverted into the right atrium. The preferred surgical preoperative information about the anomaly can be critical in
approach involves transaction of right SVC above the right planning surgical procedure.
upper pulmonary vein and anastamosis of the transacted caval
end to the right atrial appendage.26 ANOMALIES OF THE INFERIOR VENA CAVA
A B C
Figures 12A to C: A. 3-year-old girl with distension of abdomen; B. Simultaneous injection of contrast in inferior vena cava (IVC) from below
through femoral vein approach and from above through jugular vein approach shows a membrane in IVC with tortuous collaterals; C. Check 219
venogram from IVC after membrane was punctured by Brockenbrough needle and dilatation with Inoue balloon, illustrates opened up IVC
(arrow) and disappearance of large collateral. RA = Right atrium
http://vip.persianss.ir
3
Defects in Atriovenous and Pulmonary Arteriovenous Connections
A B
Figures 14A and B: Left sided inferior vena cava (IVC): A. Draining
into hepatic IVC and into right atrium (RA); B. Draining through
hemiazygos vein into left superior vena cava (LSVC) into the coronary
sinus (CS)
Treatment
Surgical correction to redirect the venous blood into the right
atrium.
http://vip.persianss.ir
3
References 21. Raghib G, Ruttenberg HD, Anderson RC, et al. Termination
of left superior vena cava in left atrium, atrial septal defect,
Defects in Atriovenous and Pulmonary Arteriovenous Connections
1. Geva T, Van Praagh S. Abnormal systemic venous connections. and absence of coronary sinus; a developmental complex.
In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF (Eds). Moss Circulation. 1965;31:906-18.
and Adams’ Heart Disease in Infants, Children, and Adolescents: 22. Castaneda AR, Jonas RA, Mayer JE Jr, et al. Cardiac Surgery
Including the Fetus and Young Adults, 7th edn. Lippincott of the Neonate and Infant. Philadelphia: WB Saunders, 1994.
Williams and Wilkins, Philadelphia; 2008. pp. 792-817. pp. 152-3.
2. Sadler TW. Langman’s Medical Embryology. 7th edn. 23. Irlich TN, Herzer JA, Schulte HD, et al. Left persisting, singular
Baltimore: Williams and Wilkins, 1995. pp. 221-3. superior vena cava and pacemaker electrode implantation by
3. Marshall J. On the development of the great anterior veins in man right cephalic vein [in German]. Z Kardiol. 1976;65:575-82.
and Mammalia. Philos Trans R Soc Lond. 1850;140:133-70. 24. Lenox CC, Zuberbuhler JR, Park SC, et al. Absent right
4. McCotter RE. Three cases of persistent left superior vena cava. superior vena cava with persistent left superior vena cava:
Anat Rec. 1916;10:371-83. Implications and management. Am J Cardiol. 1980;45:117-22.
5. Meadows WR, Sharp JT. Persistent left superior vena 25. Bartram U, Van Praagh S, Levine JC, et al. Absent right
cava draining into the left atrium without arterial oxygen superior vena cava in visceroatrialsitussolitus. Am J Cardiol.
unsaturation. Am J Cardiol. 1965;16:273-79. 1997;80:175-83.
6. Sanders JM. Bilateral superior vena cava. Anat Rec. 1946;94: 26. Van Praagh S, Geva T, Lock JE, et al. Biatrial or left
657-62. atrial drainage of the right superior vena cava: Anatomic,
7. Geissler W, Albert M. Persistent left superior vena cava and morphogenetic, and surgical considerations report of three new
mitral stenosis [in German]. Z Gesamte Inn Med. 1956;11:865- cases and literature review. Pediatr Cardiol. 2003;24:350-63.
74. 27. Chin AJ. Subcostal two-dimensional echocardiographic
8. DeLeval MR, Ritter DG, McGoon DC, et al. Anomalous identification of right superior vena cava connecting to left
systemic venous connection—surgical considerations. Mayo atrium. Am Heart J. 1994;127:939-41.
Clinic Proc. 1975;50:599-610. 28. Kershner L. Morphologie der vena cava inferior. Anat Anz.
9. Nash EN, Moore GW, Hutchins GM. Pathogenesis of persistent 1888;3:808-23.
left superior vena cava with coronary sinus connection. Pediatr 29. Gerlis LM, Ho SY. Anomalous subaortic position of the
Pathol. 1991;11:261-9. brachiocephalic (innominate) vein: A review of published
10. Van Praagh S, O'Sullivan J, Brili S, et al. Juxtaposition of reports and report of 3 new cases. Br Heart J. 1989;61:540-5.
the morphologically right atrial appendage in solitus and 30. Konstantinov IE, Van Arsdell GS, O’ Blenes S, Roy N,
inversus atria: A study of 35 postmortem cases. Am Heart J. Campbell A. Retroaortic innominate vein with coarctation of
1996;132:382-90. the aorta: Surgical repair and embryology review. Ann Thorac
11. Cormier MG, Yedlicka JW, Gray RJ, Moncada R. Congenital Surg. 2003;75:1014-6.
anomalies of the superior vena cava: a CT study. Semin 31. Kim SH, Chung JW, Im JG, et al. Subaortic left innominate vein:
Roentgenol. 1989;24:77-83. Radiologic findings and consideration of embryogenesis. J
12. Cha EM, Khoury GH. Persistent superior vena cava: radiologic Thorac Imaging. 1999;14:142-6.
and clinical significance. Radiology. 1972;103:375-81. 32. Minami M, Noda M, Kawauchi N, Shirouzu I, Nakajima J,
13. Schummer W, Schummer C, Hoffmann E, Gerold M. Persistent Araki T, et al. Postaortic left innominate vein: Radiological
left superior vena cava: clinical implications for central venous assessment and pathogenesis. ClinRadiol. 1993;48:52-6.
cannulation. Nutr Clin Pract, 2002;17:304-8. 33. Choi JY, Jung MJ, Kim YH, Noh CI, Yun YS. Anomalous
14. Tak T, Crouch E, Drake GB. Persistent left superior vena cava: subaortic position of the brachiocephalic vein (innominate
incidence, significance and clinical correlates. Int J Cardiol. vein): An echocardiographic study. Br Heart J. 1990;64:385-7.
2002;82:91-3. 34. Chen SJ, Liu KL, Chen HY, et al. Anomalous brachiocephalic
15. Ratliff HL, Yousufuddin M, Lieving WR, et al. Persistent left vein: CT, embryology and clinical implications. Am J
superior vena cava: case reports and clinical implications. Int J Radiol. 2005;184:1235-40.
Cardiol. 2006;113:242-6. 35. Kulkarni S, Jain S, Kasar P, Garekar S, Joshi S. Retroaortic left
16. Troost E, Gewillig M, Budts W. Percutaneous closure of a innominate vein—Incidence, association with congenital heart
persistent left superior vena cava connected to the left atrium. defects, embryology, and clinical significance. Ann Pediatr
Int J Cardiol. 2006;106:365-6. Cardiol. 2008;1:139-41.
17. Ghadiali N, Teo LM, Sheah K. Bedside confirmation of 36. Phillips E. Embryology, normal anatomy, and anomalies. In:
a persistent left superior vena cava based on aberrantly Ferris EJ, Hipona FA, Kahn PC, Phillips E, Shapiro
positioned central venous catheter on chest radiograph. Br J JH, (Eds). Venography of the inferior vena cava and its
Anaesth. 2006;96:53-6. branches. Baltimore, Md: Williams and Wilkins, 1969. pp. 1-32.
18. Dearstine M, Taylor W, Kerut EK. Persistent left superior 37. Moller JH, Nakib A, Anderson RC, et al. Congenital cardiac
vena cava: chest X-ray and echocardiographic findings. disease associated with polysplenia: A developmental complex
Echocardiography. 2000;17:453-5. of bilateral left-sidedness. Circulation. 1967;36:789-99.
19. Sarodia BD, Stoller JK. Persistent left superior vena cava: case 38. Effler DB, Greer AE, Sifers AE. Anomaly of the vena
report and literature review. Respir Care. 2000;45:411-26. cava inferior: Report of fatality after ligation. JAMA.
222 20. Ootaki Y, Yamaguchi M, Yoshimura N, et al. Unroofed 1951;146:1321-3.
coronary sinus syndrome: diagnosis, classification, and surgical 39. Latimer HB, Virden HH. A case of complete absence of the
treatment. J Thorac Cardiovasc Surg. 2003;126:1655-6. inferior vena cava. J Kansas Med Soc. 1944;45:346-53.
15
40. Ruscazio M, Van Praagh S, Marrass AR, et al. Interrupted 50. Cohen MI, Gore RM, Vogelzang RL, et al. Accessory
inferior vena cava in asplenia syndrome and a review of the hemiazygos continuation of the inferior vena cava: CT
223
http://vip.persianss.ir
C hapter
IntroduCtIon
ClAssIfICAtIon
The pulmonary venous anomalies can be grouped as:
1. Anomalous connections.
2. Anomalous drainage with normal connections.
3. Stenotic connections.
4. Abnormal numbers of pulmonary veins.
C D
Embryology Figures 1A to D: Development of pulmonary veins: A. At 27 to 29 days
of gestation, the primordial lung buds are enmeshed by the vascular
The knowledge of the pulmonary venous development is plexus of the foregut (the splanchnic plexus). A small evagination
essential to understand the anatomical abnormalities (Figures 1 can be seen in the posterior wall of the left atrium to the left of the
A to D). Recent work has demonstrated that they develop from developing septum secundum; B. By the end of the 1st month of
gestation, the common pulmonary vein establishes a connection
the dorsal mesocardium within the posterior mediastinum. between the pulmonary venous plexus and the sinoatrial portion of
They arise as a new channel and not as an outpouching from the heart; C. Next, the connections between the pulmonary venous
the sinus venosus that is forming the systemic veins that join plexus and the splanchnic venous plexus involute; D. The common
the right atrium. In the early part of the development, lungs pulmonary vein (CPV) incorporates into the left atrium so that the
individual pulmonary veins connect separately and directly to the left
get enmeshed by the vascular plexus from the foregut (i.e. atrium. LA = Left atrium; LCCV = Left common cardinal vein; LLB =
splanchnic). As the differentiation progresses these develop Left lung bud; RA = Right atrium; RCCV = Right common cardinal vein;
into the pulmonary vascular bed. At 25 to 27 days’ gestation, RLB = Right lung bud; UV = Umbilical vein
the developing pulmonary venous plexus retains connections PArtIAl AnomAlous PulmonAry VEnous 16
to the right superior vena cava (SVC), left SVC and portal ConnECtIon
system. No direct communication to the left atrium exists. At
A B
Figures 2A and B: A. By Day 40, the primitive connections from the pulmonary vascular bed to the cardinal veins should have regressed, but
in partial anomalous venous connections, the anomalous connections persist; B. At term, the anomalous connection will have developed into 225
anomalous pulmonary veins draining most commonly into the SVC on the right, or the brachiocephalic vein on the left. IVC = Inferior vena cava;
LA = Left atrium; RA = Right atrium; SVC = Superior vena cava
http://vip.persianss.ir
3 Other connections such as to the coronary sinus are also
known, however they are rare. Right pulmonary veins are
more commonly involved than the left. Most of the time when
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
Pathophysiology
A B The principal physiological hemodynamic abnormality is
due to the pre-tricuspid atrial level left to right shunt causing
increased pulmonary blood flow. This left-to-right shunt leads
to the dilatation of the right heart chambers and the main
pulmonary artery. The left heart chambers are not dilated and
have preserved function. The magnitude of the left-to-right
shunt is determined by:
1. Number of anomalously connecting veins.
2. Severity of obstruction.
3. Compliance of the chamber into which the anomalous
veins connect.
4. Relative resistances of the normal and abnormal pulmonary
C D veins.
A greater number of veins draining anomalously, results in
Figures 3A to D: Common forms of partial anomalous pulmonary more blood returning to the right side of the heart. The defect
venous connections (PAPVC): A. Anomalous connection of the right
clinically becomes significant when more than 50 percent of
pulmonary veins (RPV) to the SVC. A high or sinus venous defect is
usual in this anomaly; B. Anomalous connections of the RPV to the the veins return anomalously. The source of the returning blood
IVC. The right lung commonly drains by 1 pulmonary vein without plays a role in determining the clinical effect of the defect.
its usual anatomic divisions. Parenchymal abnormalities of the right In the upright posture, individual blood flow to the lungs is
lung are common, and the atrial septum is usually intact. This type
directed primarily to the lower and middle lobes. Therefore,
of PAPVC is found in Scimitar syndrome; C. Anomalous connection
of the left pulmonary veins (LPV) to the left innominate vein (LIV) one would expect more blood to return to the right side of the
by way of a left vertical vein (LVV). An additional left-to-right shunt heart in individuals in whom the anomalous connection drains
may occur through the ASD; D. Anomalous connection of the LPVs either the right middle and lower lobes or the left lower lobe.
to the coronary sinus (CS). IVC = Inferior vena cava; LA = Left
Though the above mentioned factors influence the amount
atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle;
SVC = Superior vena cava; VV = Vertical vein of the blood returning to the right side of the heart, there is
no right to left shunt. The associated non-cardiac conditions
like pulmonary parenchymal disease exacerbate clinical
progression.
veins attach to the lower side of the SVC or the SVC–right PAPVC is often associated with an atrial septal defect (ASD),
atrium junction. especially of the sinus venosus type. Sinus venosus defects
2. Right pulmonary vein to the right atrium. The right physiologically allow an atrial level communication, but are not
pulmonary veins connect directly to the right atrium. true ASDs as they do not involve septum. In 20 percent of the
3. Right pulmonary veins to the inferior vena cava (Scimitar patients, the atrial septum is intact. PAPVC may also occur in
syndrome). The anomalous right pulmonary vein, generally patients with visceral heterotaxy and polysplenia.4
draining the entire right lung, descends in a cephalo-caudad
direction toward the diaphragm and then curves sharply to scimitar syndrome
the left to join the inferior vena cava (IVC) or IVC–right
atrium junction, superior to the hepatic vein orifices. Scimitar or pulmonary venolobar syndrome is a rare but
4. Left pulmonary veins to the left innominate vein. The left well known congenital cardiovascular defect that includes
pulmonary veins may connect to the left innominate vein a hypoplastic right pulmonary artery and right lung, which
by way of an anomalous vertical vein. leads to the displacement of the cardiac structures into the
5. Bilateral PAPVC. A rare form of PAPVC. Most commonly, right hemithorax, anomalous systemic arterial supply to the
the atrial septum is intact, the left superior pulmonary right lung and a characteristically curved anomalous right
vein attaches to the left innominate vein by way of an pulmonary vein that drains into the IVC. This resembles
226 anomalous vertical vein, and the right superior pulmonary the curved Middle Eastern Ottoman sword “Scimitar”5
vein attaches to the SVC–right atrium junction (Figures 4A to C). The Scimitar syndrome was first described
16
http://vip.persianss.ir
3
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
Figure 5: Typical 12-lead electrocardiogram in a patient with PAPVC. There is an rsR’ pattern in lead V1 consistent
with mild right ventricular conduction delay or volume overload. The P waves are not peaked in this example
A B
Figures 6A and B: A. Subcostal view showing the anomalous connection of the pulmonary vein into the right atrium; B. “Crab view” with
2-dimensional and color Doppler demonstrating the absence of the right upper and right lower pulmonary veins. Ao = Aorta; LA = Left atrium;
LV = Left ventricle; LLPV = Left lower pulmonary vein; LUPV = Left upper pulmonary vein; RA = Right atrium; RPA = Right pulmonary artery;
RMPV = Right middle pulmonary vein; RPV = Right pulmonary vein
Subcostal view is particularly useful in patients with found the prevalence of previously undiagnosed PAPVC to
Scimitar syndrome. Majority of the patients with PAPVC be 0.2% in a general adult population. With advent of newer
have enlargement of right atrium and right ventricle. It is multi-slice CT machines, scan can be performed in few
recommended that TEE be performed in any patient with right seconds without the need for breath holding. Also images can
ventricular enlargement in whom transthoracic examination is be reconstructed in three dimensions with a better anatomical
inconclusive7 (Figures 6A and B). description. This helps the surgeon in deciding the technique
and approach8 (Figure 7).
ComPutEd tomogrAPhy
mAgnEtIC rEsonAnCE ImAgIng
Computed tomography (CT) is being increasingly used for
228 visualization of the anomalous connections of the pulmonary Cardiovascular magnetic resonance imaging (CMR) is an
veins since 1990. A recent retrospective series of CT scans invaluable tool for the diagnosis of PAPVC in adult patients.
16
http://vip.persianss.ir
3 Cardiac Catheterization Prognosis
As non-invasive diagnostic modalities have increased the The prognosis of PAPVC is similar to an isolated ASD with
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
sensitivity and specificity of diagnosis of PAPVC, the need for a comparable left-to-right shunt. Patients with Scimitar
diagnostic catheterisation has decreased. The most definitive syndrome have a worse outcome than the other types of
technique for diagnosing PAPVC at cardiac catheterisation is PAPVC, especially those with early onset of symptoms. Of
to enter the right pulmonary vein directly with the catheter and those cases that require surgical repair, operative mortality
perform a selective angiogram in it or selective left pulmonary rates are low (under 1%). Systemic or pulmonary vein
artery angiogram in levophase illustrates the left pulmonary obstruction as well as sinus node dysfunction has been rarely
veins draining into vertical vein, then horizontal vein (left reported.10
innominate vein) and into right atrium (RA) at the superior
vena cava (SVC) and RA junction (Figure 9). This will totAl AnomAlous PulmonAry VEnous
help to demonstrate the venous drainage pattern, associated ConnECtIons
atrial level communication, measure pulmonary pressures
and calculate Qp: Qs. Oximetry is of little value when the
anomalous connection is to the IVC, as there is selective
definition
streaming of the oxygenated blood from the renal vein. In this condition, all the pulmonary veins have abnormal
Inability to pass the catheter from the right atrium to the left connection to the systemic circulation. They do not connect
atrium or a difference in right atrial pressure and pulmonary directly to the left atrium.
wedge pressure is suggestive of PAPVC with intact septum. The term total anomalous pulmonary venous connection
(TAPVC) implies an absence of a direct connection between
management the pulmonary veins and the left atrium. The pulmonary
veins connect via systemic veins to the right atrium and are
Surgery is the definitive treatment. Infants with Scimitar often obstructed. This results in mixing of deoxygenated
syndrome may develop respiratory distress and need early and oxygenated blood in the right atrium. The reported
surgical treatment. Indications for surgery are Qp : Qs > 2, incidence for TAPVC ranges from 0.4 to 2 percent from
recurrent respiratory tract infections, Scimitar syndrome prior autopsy studies.11 Males and females are equally
and when surgery is being considered for other indications. affected, however few studies have demonstrated higher
Surgery is usually carried out between 2-5 years of age under incidence in males especially in the infracardiac type.12
cardiopulmonary bypass. Surgical mortality is less than 1 The non-cardiac conditions associated with TAPVC are
percent. Postoperative complications include SVC obstruction asplenia or polysplenia heterotaxy syndromes. There is no
and atrial arrhythmias. known genetic inheritance pattern. Maternal lead exposure
is often considered as an etiology.13 Often TAPVC occurs
as an isolated lesion except for the associated inter-atrial
septal defect. However, it is known to be associated
with other cardiac malformations like transposition of
the great arteries, pulmonary atresia, truncus arteriosus,
atrioventricular septal defect and single ventricle
physiology.14
Anatomy
A number of classification schemes for describing the different
types of TAPVC have been proposed. The most widely
adopted system (Darling et al)15 classifies TAPVC according
to the anatomic location of the anomalous connection (Figures
10A to D).
• Type 1 - Supracardiac type of total anomalous pulmonary
venous connection
• Type 2 - Cardiac type of total anomalous pulmonary venous
connection
• Type 3 - Infracardiac type of total anomalous pulmonary
Figure 9: Cardiac catheterization: Pigtail angiogram in LPA demon- venous connection
230 strating the anomalous drainage of the left pulmonary veins through
• Type 4 - Mixed type of total anomalous pulmonary venous
the vertical vein and horizontal vein (left innominate vein) into right
atrium (RA) at the superior vena cava (SVC) and RA junction connection
course of the vein is between the left pulmonary artery and the 16
left bronchus, these two structures clasp the venous channel
producing the bronchopulmonary (hemodynamic) vice, which
http://vip.persianss.ir
3 Pathophysiology in obstructed venous return. Rare manifestations (especially
in infracardiac TAPVC) include sudden death, unconjugated
TAPVC results in complete mixing of the systemic and hyperbilirubinemia and hematemesis. The infants with
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
pulmonary blood. There is an obligatory right-to-left shunt as large inter-atrial communication present at later age. They
the pulmonary venous return is to the systemic veins. Most often present with failure to thrive, tachypnea and frequent
of the times the right-to-left shunt occurs at the atrial level respiratory tract infections. On examination, neonates with
and rarely it has been reported at ventricular level or at ductal infracardiac TAPVC are sick, cyanosed with signs of poor
level with intact septum. Hence, the mixed venous blood may peripheral perfusion. Findings are similar to an ASD, with
enter the right ventricle and the pulmonary circuit or may a wide split second heart sound and mid systolic murmur.
pass through the obligatory right-to-left atrial communication Precordium is quiet. Sometimes there is a venous hum heard
and fill the left ventricle (LV) and the systemic circulation. A below the left clavicle especially in supracardiac TAPVC to
non-restrictive ostium secundum ASD is seen in 20% of the the left innominate vein. It differs from other venous hums in
patients with simple TAPVC.16 Remaining 80 percent of the that it persists even with compression of the neck veins and is
infants have PFO with restricted right to left shunt. As the not louder in diastole. P2 is loud. Hepatomegaly may be seen
neonates grow there is a decrease in the pulmonary vascular when the anomalous drainage is to the portal vein.18 Infants
resistance which further decreases the right to left shunt. without pulmonary venous obstruction present with typical
Most of the blood recirculates through the low resistance features of an ASD. The precordium is hyperdynamic with
pulmonary circulation resulting in increased pulmonary blood wide fixed splitting of the second heart sound.
flow and decreased systemic output. These neonates manifest
with respiratory distress and hypoxemia. They typically have Investigations
elevated right atrial pressures, pulmonary artery hypertension
and low cardiac output. When the shunt is at the level of the
Chest Radiography
atrium there is tendency for the fetal pattern of the circulation
to be maintained. In case of the infradiaphragmatic variant of In newborns with severe pulmonary venous obstruction,
TAPVC, the oxygenated blood ascending the inferior caval cardiac silhouette is normal or small with ground glass
vein towards the right atrium is directed towards the left appearance of the lung fields. Sometimes the findings may be
atrium. Accordingly, the systemic arterial oxygen saturation misinterpreted as RDS, which is more common in the newborn
is relatively higher than the pulmonary arteries. Conversely period. However, unlike obstructive TAPVC, in RDS usually
,in supracardiac TAPVC, oxygenated blood tends to be homogeneous patchy infiltrates along with air-bronchograms
directed down the SVC and through the tricuspid valve into are noted.19,20
the pulmonary circulation. Hence, the pulmonary oxygen In patients without the obstructive physiology, the X-ray
saturation is likely to be more than systemic. findings are similar to those with right-sided volume overload.
Obstruction to the pulmonary venous return results in the In older patients the pulmonary trunk may be prominent;
rise of the pulmonary capillary wedge pressure and rapid sometimes the left vertical vein may be prominent when that is
progression to pulmonary edema. With further rise of the the site of anomalous connection. This gives rise to snowman
pulmonary capillary pressure, the RV compliance decreases appearance also called WC Fields heart (Figures 11A and B).
leading to increase in the right atrial pressure and right-to-left
atrial shunt. This ultimately leads to systemic hypoxemia and Electrocardiography
metabolic acidosis. If the ductus is still open this will again lead
to increased right-to-left shunt and worsening of the systemic Right axis deviation with a clockwise frontal plane loop and
hypoxemia and pulmonary oligemia. The progressive rise in the right ventricular hypertrophy is seen. V1 usually shows an
metabolic acidosis leads to multiorgan failure. The outcome will rsR′ pattern, though a qR is seen in four-fifths of the patients,
be fatal without the relief of the pulmonary venous obstruction. which indicates severe pulmonary hypertension. By the age of
3 to 4 months most of the patients have features of right atrial
Clinical Presentation enlargement on ECG.
lower and right upper pulmonary veins, while the suprasternal Intracardiac TAPVC: The coronary sinus itself will be
approach, given a good window, can demonstrate all four. A dilated. It can be dilated because of a persistent left SVC
universal finding in TAPVC is right-sided volume overload, as well. Thus, delineating the connection of the confluence
with enlargement of the right atrium, right ventricle, and into the coronary sinus is imperative. The pulmonary venous
main pulmonary artery. The clue to diagnosis is the exclusive confluence is directly posterior to the left atrium. It is thus
right to left shunt at the atrial level. An essential element is well visualized in the parasternal, apical four-chamber and
identifying the size and location of each vein and how and subcostal views (Figure 12).
where they enter the heart. This is especially important Supracardiac TAPVC: The pulmonary venous confluence
because it has been shown that the sum of the individual is usually superior to the left atrium and is thus best visualized
vein sizes is an independent risk factor for postoperative in the parasternal views. It may also be seen from the subcostal
mortality. Specifically, small veins before surgery lead to long-axis views. Drainage to the SVC is either direct or
higher postoperative mortality.25 In patients who are difficult through the left vertical vein. Left vertical vein connects to
to image with TTE, TEE may provide better visualization of the brachiocephalic vein which is better visualized in supra-
the pulmonary veins and their site of drainage because of their sternal view (Figures 13A and B). An easy way to identify and
posterior location.26 trace the left vertical vein is to inject contrast bubbles into the
left arm.
Localizing the Confluence of Pulmonary Veins Infracardiac TAPVC: The pulmonary veins usually converge
just above the diaphragm. Therefore, the pulmonary venous
The suprasternal view or parasternal short axis view better confluence is often small and inferior to the left atrium or
demonstrates the venous confluence in TAPVC. Confluence may not exist as a distinct, separate chamber. The descending
is seen as an echo free non-pulsatile structure posterior to the vein is better demonstrated in the sub-costal long axis view
left atrium. It has a separate venous egress connecting to the (Figures14A and B). It should be differentiated from the aorta
systemic vein. Supracardiac TAPVC can generally be best and the IVC. It is non-pulsatile and doesn’t connect to either
seen from the parasternal imaging and infracardiac TAPVC atrium. Another easier way to differentiate it from the IVC is
is best visualized from subcostal views, however, multiple to inject contrast micro-bubbles into the leg veins.
views are often used. For obvious reasons, it is often difficult Mixed Form of TAPVC: This form of TAPVC is suspected
to localize the pulmonary venous confluence in neonates with when only two pulmonary veins are seen to enter the venous
RDS. Because of its size, shape and posterior location, the confluence in multiple views and planes. Special attention
pulmonary venous confluence can sometimes be difficult to should be paid to the coronary sinus and the innominate vein,
image directly, even by TEE. as potential sites of drainage. Echocardiography can be used
233
http://vip.persianss.ir
3
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
Figure 12: Cardiac total anomalous pulmonary venous connection (type II). Gray-scale and color Doppler echocardiographic images show
common pulmonary vein confluence (PVC) posterior to heart that empties into the right atrium (RA). LA = Left atrium; LV = Left ventricle
A B
Figures 13A and B: Suprasternal: A. and apical B echocardiographic planes demonstrating a pulmonary venous confluence (PVC) posterior
to the left atrium (LA) that is being drained by a vertical vein (VV). The apical four-chamber view; B. More clearly shows the VV arising from the
PVC and heading cephalad. Ao = Aorta; LV = Left ventricle; RA = Right atrium
to trace the final common pathway of pulmonary venous detection of obstruction by cross sectional imaging and color
drainage into the systemic vein. Obstruction in the pathway Doppler (Figure 15).
is recognized by the turbulent flow and pulse wave Doppler
234
offers an objective measure. The presence of a focal increase Computed Tomography and Magnetic Resonance Imaging
in flow velocity (~2 m/sec) with a continuous, non-phasic
flow pattern distally is a characteristic finding. A sensitivity These non-invasive modalities of imaging are of great help
of 100% and specificity of 85 percent have been claimed for in diagnosis and pre-operative work up. Considering the
16
http://vip.persianss.ir
3 performing the angiogram. The oximetry will demonstrate the umbilical vein is fully saturated, confirming the diagnosis.
step-up of the saturation to > 90 percent in the right atrium. The catheterization also gives the opportunity to perform the
Saturations in the right ventricle and pulmonary circulation interventions; however the catheter-based interventions are
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
are usually identical; however, it should be noted that because proved to be ineffective and are not typically undertaken.
of the streaming and incomplete mixing there could be a small Balloon or blade atrial septostomies were previously
difference in saturation. In TAPVC, the oxygen saturation in performed as a palliative measure, but they only delayed
the right atrium usually ranges between 80 percent and 95 definitive repair. The percutaneous stenting of the pulmonary
percent, and saturations in the right atrium, right ventricle, vein is largely ineffective and should not be undertaken.29,30
pulmonary artery, left atrium, left ventricle, and systemic
arteries are nearly identical. The right ventricular and differential diagnosis
pulmonary arterial pressures are usually suprasystemic with
obstructed TAPVC, but right atrial pressures are normal or Pulmonary venous atresia also presents as TAPVC with
nearly so. Pulmonary artery wedge pressure is elevated, severe pulmonary venous obstruction. Clinically, these two
whereas left atrial pressure is low. The size of the atrial conditions are indistinguishable. However, the unobstructed
communication is important for left heart preload and its size variant of TAPVC needs to be distinguished from other
can be determined at catheterization using an inflated balloon conditions like transposition of great vessels with ventricular
catheter. An interatrial communication less than 5 mm in septal defect. Atrioventricular septal defect with common
diameter is definitely restrictive.28 Selective pulmonary atrium can be distinguished from this condition on the basis
arteriography is usually diagnostic. Following injection and of ECG. Other conditions likely to cause mild cyanosis and
passage of the opaque dye through the pulmonary fields, the heart failure need to be distinguished.
dye collects in the pulmonary venous channels and clearly
outlines the anomalous connection. Rarely after selective management
left pulmonary artery angiogram in levophase we can see
the left pulmonary veins (LPVs) draining into azygos system Surgery is the only intervention with proven short and long-
(Figure 17A). Sometimes the right heart catheter through the term success for TAPVC. As a matter of fact, TAPVC is the first
azygos system can enter the right pulmonary veins (RPVs). condition in which neonatal open heart surgery was performed.
The hand injection of contrast can confirm the RPVs draining TAPVC with severe pulmonary venous obstruction requires
into azygos system (Figure 17B). If selective injection of urgent or emergent surgical intervention. Preoperatively
the contrast material into the anomalous venous channel is medical treatment needs to be started to stabilize the patient.
contemplated in the patient with TAPVC with obstruction, Neonatologists often start prostaglandin infusion in newborns
the injection should be done by hand. In a newborn with with respiratory distress and cyanosis considering the possibility
TAPVC to the portal venous system, blood obtained from the of ductus dependent circulation. It was considered dangerous
A B
236 Figures 17A and B: A. Angiogram in LPA in levophase shows left pulmonary veins (LPVs) draining into azygos system; B. Right heart catheter
through the azygos system into right pulmonary vein (RPV) and hand injection of contrast shows RPV draining into azygos vein. LPA = Left
pulmonary artery; LPV = Left pulmonary vein; RPV= Right pulmonry vein. Image courtsey: Dr IB Vijayalakshmi
in case of TAPVC with obstructive pulmonary circulation, as pulmonary tuberculosis or invasion by a tumor. Congeni- 16
it can increase the pulmonary blood flow and hence worsening tal pulmonary vein atresia is usually associated with other
the respiratory distress. However, Bullaboy et al argued that cardiac malformations. It may occur in either lung, with no
http://vip.persianss.ir
3
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
Cardiac Catheterization
A pulmonary catheterization can be accomplished by the right
side venous or left side arterial approaches. Although, a trans-
septal puncture is needed to enter the pulmonary veins, in the
case of isolated pulmonary vein stenosis without interatrial
communication, Bahl VK et al described an alternative
retrograde non-trans-septal arterial approach for the pulmonary
vein using steerable left atrial catheter.44 The diagnostic
features include the difference between the left atrial pressure
and the pulmonary artery wedge pressure and the preferential
flow occurring in the contralateral lung when unilateral
pulmonary venous stenosis is associated with a left-to-right
shunt. Pulmonary angiography shows the constriction of the
affected pulmonary vein and the slow clearance of the contrast
medium from one lung in the case of unilateral pulmonary Figure 20: Pulmonary artery wedge angiogram of a patient with
severe left superior pulmonary vein stenosis caused by radiofrequency
venous stenosis. Pulmonary arterial wedge angiography ablation for atrial fibrillation. Note the balloon catheter wedged in the
238 (Figure 20) may be a better technique to demonstrate the precise superior segment of the left lung, which allows excellent visualization
anatomy of the pulmonary venous stenosis than pulmonary of the vein on levophase
arteriography, where selective pulmonary venous injection arteries, suggesting that the hemodynamic effect of unilateral 16
is preferred especially in cases with isolated pulmonary vein pulmonary vein stenosis is reflected in the caliber change in
stenosis.45 Pulmonary arteriography is often disappointing the branch pulmonary arteries. The computed tomography
A B
Figures 21A and B: Contrast-enhanced magnetic resonance angiograms, reformatted in slanted coronal planes, reveal
complete occlusion of the left upper (LUPV) and left lower (LLPV) pulmonary veins. A. The left middle pulmonary vein (LMPV)
has an unobstructed connection to the left atrium (LA); B. Collateral channels (arrows) are seen between the peripheral 239
branches of the unobstructed LMPV and the branches of the obstructed LUPVs and LLPVs. Ao = Aorta; LA = Left atrium;
RA = Right atrium; RLPV = Right lower pulmonary vein; RPA = Right pulmonary artery
http://vip.persianss.ir
3 Prognosis Echocardiography
Most patients will die before reaching adulthood, and It is very difficult to visualize the small pulmonary venous
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
frequently much sooner.37 The mode of demise is usually confluence. The features that should raise the possibility of
a pulmonary hypertensive crisis, intercurrent pulmonary presence of this condition include presence of right-to-left
infection, or hemoptysis. Breinholt et al found a mortality rate shunt through the foramen ovale, pulmonary hypertension
of 83 percent in patients with 3 or 4 stenosed pulmonary veins and inability to visualize the pulmonary vein or its confluence
versus zero percent in patients with 1 or 2 stenosed pulmonary entering the left atrium. The pulmonary venous return would
veins.38 More cases of mild forms of pulmonary vein stenosis not connect to right side structures.
are undoubtedly being diagnosed in relatively asymptomatic
patients as a result of increased awareness and improvements Cardiac Catheterization
in non-invasive imaging modalities. The precise natural
history of milder forms of pulmonary vein stenosis is therefore Cardiac catheterization might be required for accurate
not entirely clear. definition of the condition. However, catheterization can
be a high-risk procedure. During catheterization injection
AtrEsIA of thE Common PulmonAry VEIn of contrast material into the right ventricle causes the
persistence of the contrast in the pulmonary artery and non-
The common pulmonary vein is a transient structure normally opacification of the left atrium. Also there will be severe
identifiable only during the early stages in the development of pulmonary hypertension with desaturation in all chambers and
the pulmonary venous system. vessels.51
The term atresia of the common pulmonary vein refers to a
pattern of abnormal pulmonary venous development in which management
the individual pulmonary veins are formed, but no connection
exists between these veins and the heart or major systemic Surgery is the definitive treatment of this condition.
veins.49 Pulmonary veins converge behind left atrium and Previously, surgery carried a high mortality. But with advent
form a confluence without draining into it. of extracorporeal membrane oxygenation, its use in the
perioperative period has resulted in improved outcome.52
Pathophysiology
unIlAtErAl PulmonAry VEnous AtrEsIA
The proposed route by which blood reaches the systemic
circulation include: Unilateral pulmonary venous atresia is a rare condition carrying
1. Bronchopulmonary venous anastomoses → pleurohilar high mortality. Till now 30 cases have been reported.53 There
bronchial veins → azygos, hemiazygos and brachiocephalic is absence of the luminal continuity between the pulmonary
veins. venous drainage between one lung and the left atrium. Most
2. Pulmonary capillaries → pulmonary arteries → broncho- are diagnosed in the preschool period. It is usually diagnosed
pulmonary arterial into the systemic circuit. on lung perfusion studies. Often there is poor blood supply to
The pulmonary capillary pressure increases leading to the the affected lung. Pneumonectomy carries the better outcome
accumulation of fluid. However, there are reports of babies compared to other modalities of surgery.54
surviving for a month.49
ConClusIon
Clinical features
The abnormal embryonic pulmonary vein development may
The clinical features in the atresia of the common pulmonary result in a wide spectrum of congenital anomalies of the
vein resembles that in TAPVC. Respiratory distress and pulmonary veins. These conditions have traditionally been
cyanosis occurs in the first few hours after birth. The condition evaluated with echocardiography and angiography and now
is often misdiagnosed as RDS as there is no cardiomegaly they can be more accurately diagnosed with mutlidetector CT
and pulmonary parenchyma shows reticular pattern (due and MRI. The improved neonatal care and surgical techniques
to pulmonary venous hypertension). It can manifest as have reduced the perioperative mortality in most centers.
spontaneous pneumothorax.50
Reading a technically poor echocardiogram is like looking
Investigation at a polar bear in a snow storm.
—Lynn Y Zoiopoulos, DO
Electrocardiography reveals right ventricular hypertrophy.
240
rEfErEnCEs 20. Patton WL, Momenah T, Gooding CA, Silverman NH. The
vascular vise causing TAPVR type I to radiographically mimic
16
1. Healy JE, Jr. An anatomic survey of anomalous pulmonary TAPVR type III. PediatrRadiol. 1999;29:323-6.
http://vip.persianss.ir
3 unsuccessful treatment by trans venous balloon dilation. Am J
Cardiol. 1982. p.49.
obstruction in children? A phase-contrast magnetic resonance
study. Pediatr Radiol 2005;35:580-6.
38. Cullen S, Deasy PF, Tempany E, Duff DF. Isolated pulmonary 47. Lock JE, Bass JL, Castaneda-Zuniga W, Fuhrman BP,
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
vein atresia. Br Heart J. 1990;63:350-54;1767-72. Rashking WJ, Lucas RV Jr. Dilation angioplasty of
39. Beerman LB, Oh KS, Park SC, et al. Unilateral pulmonary vein congenital or operative narrowings of venous channels.
atresia: clinical and radiographic spectrum. Pediatr cardiol. circulation.1984;70:457-64.
1983;4:105-12. 48. Breinholt JP, Hawkins JA, Minich L, Tani LY, Orsmond GS,
40. Shone JD, Amplatz K, Anderson RC, et al. Congenital stenosis Ritter S, Shaddy E. Pulmonary vein stenosis with normal
of individual pulmonary veins. Circulation. 1962;26:574-81. connection: associated cardiac abnormalities and variable
41. Heyneman LE, Nolan RL, Kevinharrison J, Page McAdams outcome. Ann Thorac Surg. 1999;68:164-8.
H. Congenital Unilateral Pulmonary Vein Atresia: Radiologic 49. Lucas Jr RV, Woolfrey BF, Anderson, et al. Atresia of the
Findings in Three Adult Patients. AJR 2001;177:681-5. common pulmonary vein. Pediatrics. 1962;29:729-39.
42. Bini RM, Cleveland DC, Ceballos R, et al. Congenital 50. Sharda JK, Kurlandsky LE, Lacina SJ, Radecki LL.
pulmonary vein stenosis. Am J Cardiol 1984;54:369-75. Spontaneous pneumothorax in common pulmonary vein
43. Samdarshi TE, Morrow WR, Helmcke FR, Nanda NC, atresia. J Perinatol. 1990;10:70-4.
Bargeron LM Jr, Pacifico AD. Assessment of pulmonary vein 51. Dudell GG, Evans ML, Krous HF, et al. Common pulmonary
stenosis by transesophageal echocardiography.Am Heart J vein atresia: The role of extracorporeal membrane oxygenation.
1991;122:1495-8. Pediatrics. 1993;91:403-10.
44. Bahl VK, Chandra S, Mishra S. Congenital stenosis of 52. Suzuki T, Sato M, Murai T, Fukuda T. Successful surgical
isolated pulmonary vein: role of retrograde pulmonary vein repair of common pulmonary vein atresia in a newborn.
catheterization. Int J Cardiol 1997;60:103-5. PediatrCardiol. 2001;22:255-7.
45. Valsangiacomo E, Levasseur S, McCrindle B, MacDonald C, 53. Shimazaki Y, Nakano S, Kato H, et al. Mixed type of total
Smallhorn J, Yoo S. Contrast-enhanced MR angiography of anomalous pulmonary venous connection with hemi-
pulmonary venous abnormalities in children. PediatrRadiol pulmonary vein atresia. Ann Thorac Surg. 1993;56:1399-401.
2003;33:92-8. 54. Kingston HM, Patel RG, Watson GH. Unilateral absence or
46. Roman KS, Kellenberger CJ, Macgowan CK, et al. How is extreme hypoplasia of pulmonary veins. Br Heart J. 1983;
pulmonary arterial blood flow affected by pulmonary venous 49:148-53.
242
C hapter
Congenital Pulmonary
17 Arteriovenous Fistula
http://vip.persianss.ir
3 coexisting congenital heart disease (CHD). Isolated exceptions vascular channels or a tangle of smaller vessels instead of
have been reported with left isomerism and atrial septal defect capillaries. They attributed the aneurysmal connection to
(ASD). Estimated minimal prevalence rate is 1 per 10,000 the transmission of arterial pressure directly through the
Defects in Atriovenous and Pulmonary Arteriovenous Connections
births.6 The incidence is 2 to 3/100,000 population. The male connection with the veins. It is suggested that all PAVFs begin
to female ratio varies from 1: 1.5 to 1.8 in various series.2 as plexus type connection for unknown reasons; aneurysms
The PAVFs are usually congenital in origin. However, arise by progressive dilatation of one or several limbs of a
they may be acquired in a variety of conditions such as small plexus.9
hepatic cirrhosis, schistosomiasis, mitral stenosis, trauma,
actinomycosis and metastatic thyroid carcinoma and even Morphology
after cavopulmonary anastomosis.4,5
The HHT is an autosomal dominant disease with frequency Morphologically PAVFs are divided into two types:
estimated at estimated as 1-2 per 100,000 persons. A wide 1. Localized lesions commonly occurring in HHT or isolated
geographic variation in disease prevalence is reported. It is PAVF.
genetically heterogeneous disease with at least 3 abnormal 2. Diffuse lesions occurring in patients with CHD, liver
chromosomal loci (9q, 12q, and a third locus). HHT gene disease, portal vein thrombosis and Glenn shunts.
has been identified as endoglin, a transforming growth factor PAVFs range from small pinpoint lesions (1 mm) to huge
(TGF) beta binding protein. Mutations in endoglin may alter tubular or saccular, multilobulated structures occupying most
cellular ability to bind TGF beta 1 with significant potential of a lobe or an entire lung. Lesions may be single or multiple,
consequences in cell regulatory mechanisms. Presumably the unilateral or bilateral. Small lesions tend to be multiple,
vascular abnormalities seen in patients with HHT may arise diffuse and located deep within the parenchyma. Larger
from such aberrations in endothelial cell regulations and malformations are usually isolated involving the subpleural
functions.8 regions of the lower lobes (65%). The airways and lung
parenchyma surrounding the malformations are normal.5
PATHOLOGY, PATHOPHYSIOLOGY AND
MORPHOLOGY Physiology
Pulmonary arteriovenous fistulas do not affect cardiac
Pathology hemodynamics.2 The PAVF creates a right to left shunt from
Anatomically PAVFs are dilated and aneurysmal vessels the pulmonary arteries to the pulmonary veins, resulting in
that directly connect pulmonary arteries to pulmonary veins systemic arterial desaturation and secondary polycythemia. If
and thus bypass the normal capillary bed, which results in the channels are small there is no significant shunting, cardiac
two important physiological consequences. First, right to output (CO) is not increased, plasma volume remains normal
left shunting occurs with the degree of shunt related to the and the pulmonary blood flow and pressure are unchanged.
number of PAVFs and their size. Second, the pulmonary The total pulmonary vascular resistance is normal, resistance
capillary bed normally acts as a filter for venous blood, blood within the arteriovenous fistula is low, but resistance in the
flowing through the PAVM bypasses this filtering process other lung segments may be elevated two-fold. Since normal
and acts as a conduit through which paradoxical systemic pulmonary artery resistance is low, the arteriovenous fistula
embolism can occur. The abnormal vascular architecture shunt does not significantly reduce the overall pulmonary
of PAVMs, their resultant right to left shunting and the vascular resistance. Because emboli and bacteria can pass
associated impairment of pulmonary filtering capacity leads directly through the fistula in to the systemic circulation,
to recognized complications including pulmonary vascular stroke and brain abscess are well-known complications.5
hemorrhage, hypoxemia and neurological sequelae.8 The The degree of shunt determines the clinical effects on the
histopathology is structural heterogeneity in the arterial and patient. If shunting is minimal the symptoms are subacute
venous components. Degenerative changes and aneurysm or absent. If right to left shunt is greater than 20 percent of
formation may be associated with vessel wall rupture. systemic CO or there is reduced hemoglobin more than 50
Patients may have hemoptysis, hemothorax and pulmonary g/L the patient will have obvious cyanosis, clubbing and
hemosiderosis.5 In a case of a surgically resected PAVF, the polycythemia. In some cases of HHT cyanosis may be hidden
pathological findings were reported as lung tissue with focal by anemia caused by epistaxis or gastrointestinal bleed. The red
abnormal proliferation of vascular channels with thick walls, cell mass and blood volume are usually increased, while plasma
along with diffuse congestion and alveolar hemorrhage of volume is normal. The peripheral oxygen saturation is low and
surrounding lung tissue and diffuse interstitial angiomatosis.7 as expected does not normalize with 100 percent oxygen.2
Mayor et al after review of 7 out of 15 pathologic specimens A high percentage of patients with PAVFs demonstrate
described distended afferent and efferent arteries and veins orthodeoxia (greater hypoxemia, while in sitting or standing).
244 with either a direct connection through one or several large This is due to the basal location of most PAVFs, because of the
gravitational shifts of pulmonary blood flow to the base of the Physical Signs 17
lung, when assuming erect posture. The tendency for increased
shunting and cyanosis with age is not well-understood. Many Abnormal physical findings occur in 75 percent of patients.
http://vip.persianss.ir
3 5 percent by this method is considered abnormal. In a study of
32 patients the shunt fraction ranged from 3.5 to 35 percent and
higher shunt fraction was observed in patients with multiple
Defects in Atriovenous and Pulmonary Arteriovenous Connections
A B C
246
Figures 2A to C: A. X-ray chest in posteroanterior view shows non-homogeneous opacity in the left upper lobe in 1 year old boy referred for
cyanosis, recurrent respiratory infection, SaO2-60 percent; B. Contrast echocardiography shows bubbles in right atrium and right ventricle with no
evidence of atrial septal defect/patent foramen ovale or ventricular septal defect. C. Bubbles of contrast echocardiography appear in left atrium
and left ventricle after 3 to 4 cardiac cycles. Courtesy: IB Vijayalakshmi
morphology, size and number of vascular lesions. It is 17
more sensitive than conventional CT and if 3D is added to
it, it gives angiographic architecture in 95 percent of cases.
Natural History
Most patients are asymptomatic in infancy and childhood.
Although rare, symptomatic infants are difficult to treat as their
age, size and the severe lung involvement are poor prognostic
factors. Beyond infancy the frequency of fatal complications
like rupture, massive hemorrhage, endoarteritis and cerebral
abscess is high. Hence elective treatment is recommended. In
one series, 27 percent of patients died in childhood or early
adult life, 12 percent were alive, but symptomatic, 37 percent
were alive and asymptomatic and 24 percent died due to
unrelated causes.5
http://vip.persianss.ir
3 who anticipate pregnancy, need treatment. Asymptomatic in isolated fistula, which is recommended in patients with
patients without hypoxia and with a feeding vessel diameter permanent bleeding secondary to intrapleural rupture or
less than 3 mm are usually monitored at least every 3 years. hemoptysis despite embolization. Morbidity, mortality and
Defects in Atriovenous and Pulmonary Arteriovenous Connections
Follow-up in this population is necessary as more than half of recurrences are low. Since most fistulas are subpleural, they
PAVF’s appear to increase in size over time. Pregnancy with are curable by resection.7
PAVF has high risk of maternal complications as the fistula Transcatheter coil/vascular plugs/and device embolization
size increases, because of vasodilatation or other hormonal has become the treatment of choice in multiple and bilateral
influences and hence increases risk of complications including arteriovenous fistulas, which are not suitable for surgery
worsening right to left shunt, pulmonary hemorrhage and (Figures 4A and B). This can also be done in patients as also in
stroke. Morbidity associated with untreated PAVF is up to 50 patients in whom thoracotomy and general anesthesia would
percent compared to about 3 percent in treated patients.10-12 carry a high risk due to massive shunting. In 1977, Portsman
Mortality figures range from 0 to 55 percent in various used home made metal coils, followed soon after by stainless
studies. The purpose of treatment is to reduce neurological steel coils and detachable balloons for embolotherapy.
complications, prevent progressive hypoxia and high output Through refinements in interventional equipment and techni
cardiac failure. Development of new symptoms at any time ques, embolization results have progressively improved. To
should prompt a re-evaluation.8 avoid device embolization (through the PAVF into systemic
circulation) transcatheter occlusion of the afferent artery or
TREATMENT fistula is done using an umbrella, coils or plugs rather than
liquid adhesives or beads. The Amplatzer vascular plug is a self-
Goals of therapy include relief of symptoms of dyspnea expandable, cylindrical device made from a nitinol wire mesh.
and fatigue, prevention of complications like hemoptysis The device is secured on both ends with platinum marker bands,
and hemothorax and prevention of sequelae of paradoxical especially designed for arterial and venous embolizations in
embolization including stroke and brain abscess. An attempt the peripheral vasculature. Various sizes of vascular plugs are
to raise the PaO2 to 60 mm Hg or higher, which represents available measuring from 4 to 16 mm (Figures 5A and B).
SaO2 of 90 percent. Excellent results have been achieved with embolotherapy and
Most patients with one or more PAVF’s are candidates the goal is to occlude all afferent arteries more than 3 mm in
for resection of the lesion. Asymptomatic patients or those diameter and to raise the systemic arterial oxygen saturation.
with small lesions (10–15 mm) or who have a small shunt The advantages of embolotherapy over surgery are that it avoids
are not treated, though their condition is followed regularly.7 thoracotomy and general anesthesia and multiple lesions can
An intervention is necessary in all symptomatic patients be embolized without significant loss of lung tissue. It appears
even with mild symptoms, whose lesions are visible in chest to be a durable form of treatment. In a series of 46 patients with
X-ray or CT scans. Excision is a highly successful procedure 82 PAVF’s followed for 2 to 4 years after embolotherapy, only
A B
Figures 4A and B: A. Right pulmonary artery angiogram in frontal view in a 1 year old boy with SaO2-60 percent shows multiple pulmonary
248 arteriovenous fistulas in the upper branch; B. Check angio after multiple coils, Amplatzer duct Occluder and vascular plug. Post procedure the
SaO2 improved to 94 percent. Courtesy: Dr IB Vijayalakshmi
17
Surgical Treatment
2 PAVF’s showed evidence of reperfusion. Even large PAVF’s
can be treated successfully with embolotherapy. In a series of The surgical treatment for PAVF’s is lobectomy, pneumon
45 patients with 52 PAVF’s with feeding arteries 8 mm or larger ectomy, subsegmental resection or ligation of the vascular
in diameter, all were successfully treated with embolization. pedicle feeding the PAVF. The first successful pneumonectomy
However, 15 percent required repeat embolotherapy for was performed in 1940 and the first segmental resection was
persistence of PAVF or recanalization after treatment.8 In 76 performed by Blalock in 1947. Current surgical treatment
adult patients, 276 PAVF’s were occluded providing persistent is segmental resection or lobectomy, removing the smallest
relief of hypoxemia, resolution of orthodeoxia and minimal amount of lung, while completely excising the PAVF. The
growth of small remaining PAVF’s. Some patients required operative mortality is 5 percent and the cure rate is 75 percent. In
multiple catheterizations.5 In another study done by White et infants or children surgical lobectomy may result in chest wall
al,9 patients with 91 PAVF’s were evaluated by super selective deformities, causing alterations in pulmonary mechanics. There
angiography and balloon embolotherapy was effective in is a long-term risk of developing arteriovenous malformation in
permanently obliterating the malformations in 14 patients contralateral lung.5
with rise in arterial PaO2 from 49 mm Hg to 65 mm Hg and Until 1978, surgical excision of solitary PAVF or the largest
in 3 patients it was not effective. Complex PAVF’s required PAVF’s in patients with multiple fistulas was considered the
occlusion of all feeding arteries.9 therapy of choice. Unfortunately in patients with multiple
Embolotherapy is successful in initially blocking the PAVF PAVF’s recurrences of symptoms occurred over 10 to 20
more than 95 percent of the time and has a low complication years as small PAVFs grew. In 1978, Tailor et al reported
rate. Depending on the size of the original PAVF, 5 to 15 successful embolotherapy using wool coils in a patient with
percent of the PAVFs may reopen over time and a new PAVF multiple PAVF’s. Despite complicating pulmonary infarction,
may grow. Therefore, it is very important to follow-up within 6 the patient recovered uneventfully with excellent results. In
months and then at least every 3 to 5 years to check the success 1980 additional PAVF’s were treated by coil embolotherapy
of the procedure.13 With the exception of diffuse PAVM’s, and balloon embolotherapy.9
embolotherapy results in improvement of oxygenation and Surgery is necessary in patients who fail to respond to
reduction in shunt fraction. Follow-up with chest X-ray/ embolotherapy, develop serious bleeding complications
CT scan, usually shows that lesions have disappeared in despite embolotherapy, have intrapleural rupture of the PAVF
1 year following embolotherapy. While a residual scar may or have untreatable contrast allergy and lesions not amenable
be seen in some patients, lack of radiological resolution to embolotherapy. Lung conservation resection, local resection
suggests recanalization of PAVM or inadequate embolization. or segmentectomy is the procedure of choice, whenever
Complications of embolotherapy are: possible. Staged bilateral thoracotomies were performed
1. Thrombosis, air embolism, arrhythmias. in a case of an extensive bilateral PAVF’s. Recently, video-
2. Pleurisy: It occurs in approximately 14 percent of patients. assisted thoracoscopy was employed in the resection of a
A delayed pleurisy 4 to 6 weeks later can also occur. small PAVF. Reported mortality is 0 percent after 1960.2 As
Paradoxical embolization occurs in less than 1 percent of with embolization it is important to follow-up these patients
patients.8 every 3 to 5 years to check for growth of new PAVF’s.13
In summary embolization has minimal morbidity and no
mortality and hence radiological intervention is the first choice CONCLUSION
of treatment in PAVF. Embolotherapy is a suitable alternative
to surgical interventions in the elderly, who are poor surgical Pulmonary arteriovenous fistula is an unusual clinical
candidates, in patients with multiple lesions and patients, who problem, which should be considered, when a suspected 249
decline surgery.2 case of cyanotic CHD is normal on clinical examination or
http://vip.persianss.ir
3 in symptomatic patients with the triad of exertional dyspnea, 3. Rodes CB. Cavernous hemangiomas of the lung with secondary
polycythemia. JAMA. 1938;110:1914-15.
cyanosis and clubbing with normal cardiac examination.
In such cases when cardiac findings are normal one should 4. SatSharma. Imaging in Artereovenous lung Malformations.
Defects in Atriovenous and Pulmonary Arteriovenous Connections
250
Sec t i on
Shunt Defects
http://vip.persianss.ir
c hapter
18 interatrial Defects
http://vip.persianss.ir
4 One of the early studies carried out in 1983 by
Cockerham et al12 who followed 87 children for which
cardiac catheterization was done at less than 4 years of age
Shunt DefectS
InteratrIal DefectS
overload predispose older patients to atrial arrhythmias such between the two ventricles when both AV valves open in
as atrial fibrillation and less commonly atrial flutter, this can diastole.
exacerbate sign and symptoms of heart failure. They are one This explains the timing of presentation for large shunts in
of the common presenting symptoms in the 4th to 5th decade infancy, which usually occurs between 6 to 8 weeks. At that
of life. Incidence can reach up to 52 percent in patients older point, the pulmonary vascular resistance drops to its normal
than 60 years of age.18,19 levels and the right ventricle becomes more compliant,
leading to increase pressure gradient between the two atria
Fixed Pulmonary Hypertension and subsequently a larger shunting volume. On the other
hand, later in life the left ventricle becomes more stiff perhaps
Pulmonary vascular disease is one of the most serious secondary to aging and ischemic changes and so the size of the
complications of ASDs, rendering the disease to be inoperable. shunt also increases, which might explain that most patients
Fortunately, this is not common at young age (14 to 18% with ASDs present in their 4th to 5th decade.16,17 Symptoms in
between 20–40 year of age)16 and occurs more frequently this age group include fatigue, dyspnea on exertion, peripheral
in female patients. It is still debatable whether this is caused edema and other symptoms of heart failure. This is rarely the
by the presence of large shunts or due to other predisposing case in children, where congestive heart failure or failure to
conditions such as thromboembolic phenomena.20 Severe form thrive are very uncommon.
of pulmonary hypertension leading to cyanosis as a result of Cyanosis as a result of right-to-left shunting can be due
reversal of the shunt (Eisenmenger syndrome) is infrequent and to high pulmonary vascular resistance (pulmonary vascular
usually present late in life. Konstantinides et al reported a mean obstructive disease) at an old age, but it also might be
age of 56 years.17 Sinus venosus defects patients are more prone secondary to direction of deoxygenated blood from the
to develop pulmonary hypertension at an earlier age, therefore, IVC through prominent eustachian valve or thebesian valve
close follow-up and early repair is warranted in this subset of through the defect to the left atrium. Differentiation between
patients.21 these two phenomena is crucial for future management.
Most of the time physical examination is unremarkable, typ-
Systemic Embolization ical physical findings include normal oxygen saturation, apart
from aforementioned conditions. Other findings include wide
The existence of a potential right-to-left shunt through fixed splitting of the second heart sound, which is an exaggera-
interatrial communication carries the risk of paradoxical tion of a normal phenomena that leads to delay in closure of the
embolization. This was confirmed by comparative studies pulmonary valve as a reflection of the dilation of the pulmonary
that found existing risk even in patients who do not have artery that warrants longer time to achieve adequate pressure to
atrial arrhythmias.17 The hazard of cardiogenic event such as close the pulmonary valve, other factors that explain this, is the
cryptogenic stroke increases dramatically in situations where prolonged emptying of the right ventricle.
the right atrial pressure increases such as in pregnancy and Auscultatory findings also include soft crescendo-
scuba diving. decrescendo ejection systolic murmur on the left upper sternal
border as a result of pulmonary blood overflow across that
Reduced Life Expectancy valve and a mid-diastolic murmur at the lower left sternal
border related to increased blood flow across the tricuspid
Secondary to pulmonary arterial thrombosis, congestive valve in larger shunts.
heart failure, paradoxical embolism and recurrent respiratory Once pulmonary hypertension develops these findings
infections. It is difficult nowadays to estimate age of survival completely change to a cyanotic patient with prominent
in patients with unrepaired ASDs in the modern era of surgical second heart sound, short systolic murmur and absent fixed
and catheter interventions. One study estimated the mortality splitting or diastolic murmur.
rate to be 0.6 to 0.7 percent per annum in the 1st decade of life
and more than 7.5 percent in the 6th decade.22 rELEvAnt invEStiGAtionS
http://vip.persianss.ir
4 This indeed is not seen in case of pulmonary obstructive landmarks and other associated lesions should be also sought.
disease; on the contrary, the lung fields at that point would be In addition, looking for hemodynamic consequences of large
oligemic. shunts, mainly right atrial and ventricular dilation, flattening
Shunt DefectS
figure 2: An electrocardiogram of 25-year-old female patient with large atrial septal defect showing normal sinus rhythm, right axis deviation and
256 rsR pattern in V1 consistent with right ventricle volume overload. aVR = Augmented vector right; aVL = Augmented vector left; aVF = Augmented
vector foot
18
InteratrIal DefectS
a B c
D e f
figures 3a to f: A 2D transthoracic echocardiogram of secundum atrial septal defect. A. Four-chamber apical view: this demonstrates the atrial
septal defect (arrow) and dilated right atrium and right ventricle; B. Left-to-right shunt seen on color Doppler; C and D. Parasternal short-axis
view showing the defect (arrow) and the deficient anterior (aortic rim) and the posterior rim confirmed shunt on color Doppler; E and F. Subcostal
sagittal view of showing the defect (arrow) and superior inferior margins with left-to-right shunt. RA = Right atrium; LA = Left atrium; LV = Left
ventricle; RV = Right ventricle; Ao = Aorta
a B c
figures 4a to c: Transthoracic 2D echocardiogram: A. Four-chamber view showing dilated right atrium and right ventricle with no ASD seen
in this view. This should raise the suspicion of the presence of a shunt; B. Looking carefully in subcostal sagittal view a sinus venosus defect is
appreciated. Notice the anomalous drainage of the right upper pulmonary vein; C. Finally, this is clearly identified in high esophageal TEE in the
biatrial long-axis view where the ASD (arrow) is seen with superior vena cava overriding the defect. RA = Right atrium; LA = Left atrium; LV = Left
ventricle; RV = Right ventricle; SVC = Superior vena cava; IVC = Inferior vena cava; RUPV = Right upper pulmonary vein 257
http://vip.persianss.ir
4
Shunt DefectS
a B
figures 5a and B: Transthoracic 2D echocardiogram of a coronary sinus defect: A. Frontal subcostal view showing a posteroinferior defect;
B. Suprasternal view showing persistent left SVC draining into the left atrium. In this particular case, the coronary sinus is completely unroofed
in what is called Raghib syndrome. RA = Right atrium; LA = Left atrium; LV = Left ventricle; RV = Right ventricle; LSVC = Left superior vena cava
Color and spectral Doppler confer a valuable method required for TEE and provides high-resolution intracardiac
for accurate evaluation of the hemodynamics too determine images for the defect, its rims and adjacent structures.
the direction of flow of the shunt, mean gradient across the
septum between the left and right atrium, estimation of the 3D Echocardiography
right ventricular systolic pressure using tricuspid velocity jet
and the acceleration of pulmonary blood flow. 3D transesophageal echocardiography has an outstanding clear
image with spatial relationship to surrounding landmarks. It is
Contrast Echocardiography useful especially when attempting to close multiple defects
percutaneously (Figures 7A and B).
Verification of the presence of interatrial communication can
sometimes be challenging, particularly if the defect is small cardiac ct scan and cardiac Mri
or the acoustic windows are not optimal in older adults.
Peripheral intravenous line can be used to inject agitated The use of cardiac computed tomography (CT) and cardiac
saline using a three-way stopcock, while imaging the atria in magnetic resonance imaging (MRI) is not routine in evaluating
4-apical view. Air bubbles should opacify the right atrium, ASDs. These non-invasive techniques are reserved for complex
negative wash out will be seen in the case of left-to-right shunt. atrial defect anatomy. They provide wide field view with
This technique is used more frequently to look for presence of detailed resolution of the defect and the adjacent structures,
right-to-left shunt at rest or during Valsalva maneuver. It is specifically the pulmonary veins without the limitation of poor
confirmed by the passage of the micro-air bubbles into the left acoustic windows sometimes encountered in echocardiography.
atrium through a PFO. Cardiac MRI has the advantage of accurately estimating
right ventricle volume and even the shunt size (Qp : Qs ratio)
Transesophageal 2D Echocardiography thus offering better physiological understanding of the defect.
On the other hand, MRI cannot be performed in patients who
Transesophageal echocardiogram, is used in adult patients have pacemakers or coils and it also requires sedation in
whom the transthoracic acoustic windows are not optimal. It is young patients.
valuable in determining the ASD size, rims and the pulmonary
venous drainage. It is also used to guide transcatheter device cardiac catheterization
closure (Figures 6A to F).
The role of cardiac catheterization in ASD has changed
Intracardiac Echocardiography considerably over the past years from a diagnostic tool to
more of an interventional function.
Another valuable guiding tool for transcatheter device closure Nevertheless the indications for diagnostic cardiac
258 of ASD using a small disposable imaging catheters in the catheterization are to calculate pulmonary vascular resistance
interventional suite. It obviates the need for general anesthesia and to assess the reactivity of the pulmonary vascular bed
18
InteratrIal DefectS
a B c
D e f
figures 6a to f: 2D Transesophageal echocardiogram of secundum atrial septal defect: A and B. Mid-esophageal 4-chamber view (0°–20°) for
mitral valve and tricuspid valve rims and with clockwise rotation of the probe, the right upper pulmonary vein (RUPV) should be readily visualized.
Color Doppler also confirms presence of left-to-right shunt as seen by the blue jet; C and D. High esophageal short-axis view (30°–40°) showing
the atrial septal defect (arrow) and the aortic rim is appreciated clearly in this view. Color Doppler is seen in D showing left- to-right shunt across
the defect; E and F. High esophageal biatrial long-axis view (90°–100°): this evaluates SVC and IVC rims accurately. RA = Right atrium; LA =
Left atrium; LV = Left ventricle; RV = Right ventricle; SVC = Superior vena cava; IVC = Inferior vena cava
in patients with pulmonary hypertension. Other indications • Equal pressure in both atria in large shunts
include partial anomalous pulmonary venous return where • Normal to mild elevation of right ventricular pressure
non-invasive data are nonconclusive for the course of these • Normal to mild elevation of pulmonary artery pressure
veins and their drainage.23 • Pulmonary vascular resistance should not exceed 4 Woods
Rarely, hemodynamic significance of atrial defects cannot units
be determined by echocardiography. Otherwise, hemodynamic • Unless there is pulmonary hypertension (Figure 8).
study is performed as part of an interventional procedure
during device closure of these defects. trEAtMEnt
http://vip.persianss.ir
4
Shunt DefectS
a B
figures 7a and B: This is a 3D transesophageal echocardiography view from the right atrium showing the outstanding 3D image
of secundum atrial septal defect and relationship to surrounding structures. This figure also shows the spatial orientation of each
of the 2D-TTE and TEE images: Long-axis view (LAX) is a superior inferoposterior cut into the defect: showing the SVC and IVC
relation to the defect. Short-axis view (SAX) is a anterior posterior cut into the defect showing the anterior (aortic rim) and posterior
rim of the defect. The 4 chamber view is a superoposterior and inferoanterior cut into the defect and this shows the relationship to the
atrioventricular valves. Ao = Aorta; CS = Coronary sinus; IVC = Inferior vena cava; LA = Left atrium; LV = Left ventricle; RA = Right atrium;
RV = Right ventricle; SVC = Superior vena cava; TV = Tricuspid valve
InteratrIal DefectS
Clinical and laboratory findings of right ventricular volume PFO. This, however, should be confirmed with diagnostic
overload can manifest with physical findings of diastolic cardiac catheterization.
flow rumble due to tricuspid regurgitation, cardiomegaly and
increase pulmonary vascular markings on chest X-ray, signs- SurGErY
of right ventricular hypertrophy on electrocardiograms and
ultimately echocardiographic findings of right ventricular
History
hypertrophy with possible paradoxical wall motion of the
ventricular septum.23,24 Dennis et al25 in 1951 reported the first surgical attempt to
Unless the infant cannot be managed medically for signs close an ASD; although this was not a success story, dramatic
of congestive heart failure (which is quite unusual in this improvement in cardiopulmonary bypass technique later in
condition), closure is recommended after the 2nd year of life 1950s led to a safe surgical closure of ASDs in the current era.
in anticipation of spontaneous closure or decrease in size.
Development of inevitable sequelae of large shunts later in technique
life further complicates the management of older patients. Atrial
arrhythmias should not preclude the closure of large defects. This is achieved by direct closure of the ASD using pericardial
This, however, should be preceded by successful cardioversion or Dacron patches and sometimes stitch closure for PFO.
or ablation before the access to left atrium is closed.23 Associated anomalies should be identified prior to surgery:
A major complication, mainly encountered in adulthood is cleft in the mitral valve in septum primum defects should
pulmonary hypertension. Incidence of such complication is be repaired at the same time, while in sinus venosus defects,
variable among studies. Careful evaluation of these patients identification of right upper/middle pulmonary venous
should include cardiac catheterization to determine the drainage should be taken into consideration during surgery.
operability and risk of closure. It allows direct measurement of Transesophageal echocardiography in the operating room
the pulmonary arterial pressure and pulmonary vasoreactivity is mandatory to identify any residual shunt after closure and
test with oxygen or nitric oxide. to rule out any AV regurgitation prior to closure of the chest.
Balloon occlusion testing temporarily in the cardiac Minimally invasive surgeries nowadays avoid midster-
catheterization laboratory can provide insight to the risk of notomy approach using different less extensive incisions for
closure in patients with reversible pulmonary hypertension or cosmetic purposes.
bidirectional shunt or in patients whose response to medical
therapy for pulmonary hypertension is evaluated prior to Follow-up and outcome
closure of the defect.
Several studies tried to identify patients at high risk of Over the past decades several studies looked at the outcome
mortality and morbidity for shunt closure. Pulmonary vascular of patients with ASDs following surgical repair.One of the
resistance (PVR) of more than 15 Woods unit was found to be major findings was the excellent outcome and low operative
a strong mortality predictor by Steele and colleagues. Patients mortality especially at a younger age ranging between 0 to 1
with less severe hypertension (PVR of 7–9 Woods units) percent. Older patients (> 60 years) have, however, a higher
improved after surgery. General consensus is to avoid closure risk.26
in patients with PVR more than 8 Woods units or if pulmonary Operative morbidities include residual shunt due to
arterial pressure exceeds 2/3 systemic pressure, net right-to- incomplete closure of the defect. Postpericardiotomy
left shunt, no response to pulmonary vasodilator therapy and syndrome resulting in pericardial and pleural effusion.27 New
failed test occlusion.20,23 onset arrhythmia after surgical closure, stroke and acute left
Two points should be mentioned here. First: elderly patients heart failure in earlier series especially at old age.26,27 Sinus
who develop left ventricular diastolic dysfunction as a result venosus defect repair can be complicated by pulmonary
of ischemic heart disease, hypertension or acquired valvular venous or SVC obstruction. Sinus node dysfunction and AV
disease are considered a high risk for closure. Elevated left conduction delay requiring permanent pacemaker have been
ventricular end-diastolic pressure reflected by high pulmonary seen more in patients following sinus venosus repair (6%).28,29
wedge pressures should be anticipated. Adequate medical Childhood long-term outcome studies demonstrated no
treatment prior to closure of the defect and balloon test cardiovascular mortality, heart failure, stroke or pulmonary
occlusion before closing the defect are advised. hypertension in any patient for more than 25 years of follow-
Second: a rare condition is called orthodeoxia-platypnea. up. Risk of development of atrial arrhythmias was only 8
In this condition, despite the finding of cyanosis, closure of the percent. Long-term survival after surgical closure in childhood
defect is considered curative. There are different hypotheses showed that no change from the general population.30 261
http://vip.persianss.ir
4 This has not been the case in adult outcome series that lower mortality rate were noticed postoperatively in this group
showed higher incidences of adverse outcomes and decreased although they usually have an expected difficult immediate
life expectancy. Murphy et al31 in a follow-up study of postoperative course.20
Shunt DefectS
a B
figures 9a and B: Amplatzer septal occluder device (AGA Medical Corporation, Plymouth, MN). The waist of the device (that correlates
with the defect size) can be seen B. The device is made of Nitinol, an alloy of nickel and titanium
262
Device Experience (MAUDE)/FDA have shown that mortality 18
with the Amplatzer device of less than 0.1 percent and rescue
operation was needed in 0.83 percent.35
InteratrIal DefectS
The more recently approved Helex septal occluder device is
used for percutaneous closure of smaller ASDs and PFO showed
similar success in a multicenter study in 2007 demonstrating low
complication rate mainly device embolization requiring catheter
retrieval (1.7%).36
Other complications of catheter-based interventions
include arrhythmias, which are usually transient in the first
3 months. A recent long-term follow-up study showed an
a incidence of 7 percent of documented arrhythmias in patients
who received the Amplatzer septal occluder between 1998
to 2002. Such arrhythmias included mainly supraventricular
tachycardia, atrial fibrillation and premature ventricular beats.
Rare reports of AV block have been described.37,38
Thrombus of the left atrial disc with risk of systemic
embolism has been reported. Although current devices are
less thrombogenic, antiplatelet therapy with clopidogrel and
Aspirin are used for 2 to 12 months. Post-procedure atrial
fibrillation and persistent atrial septal aneurysm had been
found as significant predictors for thrombus formation.39
Other serious complications such as occluder malposition
B
with impingement on surrounding structures, migration
figures 10a and B: Helex septal occluder device (WL Gore and after release, erosion to neighboring structures or cardiac
Associates, Flagstaff, AZ). The device can be seen mounted on the perforation are all rare incidents for which the patients are
preassembled delivery system. It is made of ePTFE patch material
supported by a single nitinol wire frame
observed for at least 24 to 48 hours after device closure.
The safe and effective nonsurgical option to close inter-
atrial defects should be assured by proper patient selection,
with associated anomalous pulmonary venous drainage. continuous assessment during device closure and close
Secundum atrial defects that are larger than 38 mm in diameter monitoring after deployment of the appropriate device.
or defects that have insufficient rims (< 5 mm) are also not
suitable for transcatheter device closure. concLuSion
Choice of the ASD that is amenable to transcatheter device
closure is a crucial step as is careful patient selection. High-risk Atrial septal defect is a common non-cyanotic congenital heart
patients include extremes of age: infants due to the need of large disease. Although usually carries benign course in childhood,
sheath size and risk of vessel injury and elderly patients with it has significant morbidity with advancing age. Closure of
left ventricular dysfunction. Other relative contraindications an ASD has certain indications. Safe non-surgical option via
include active infection, pregnancy, uncontrolled arrhythmias transcatheter closure is available for certain types of defects.
or conditions where antiplatelet therapy is not tolerated.
Genius is one percent inspiration and ninety-nine percent
technique perspiration.
—Aphorism
Technique of percutaneous approach includes hemodynamic
and echocardiographic assessment of the defect followed by AcknowLEDGMEntS
balloon sizing of the defect. Deployment of the device under
continuous echocardiographic guidance after selecting the The authors acknowledge Dr Qi-Ling Cao and John Bokowski,
appropriate type and size of the device. PhD, for their help in the echocardiography images in this
chapter.
Follow-up and outcome
rEFErEncES
Due to the relative short period, widespread use of
percutaneous approach of ASD closure follow-up data is 1. Porter C, Edwards W. Atrial Septal Defects. In: Moss and
limited. Nevertheless, the Manufacturer and User Facility Adams’ Heart Disease in Infants, Children, and Adolescent: 263
Lippincott Williams and Wilkins 2008:632-45.
http://vip.persianss.ir
4 2. Hoffman J, Kaplan S. The incidence of congenital heart
disease. J Am Coll Cardiol. 2002; 39:1890-1900.
21. Vogel M, Berger F, Kramer A, et al. Incidence of secondary
pulmonary hypertension in adults with atrial septal or sinus
3. Fyler DC. Atrial septal defect secundum. In: Nada’s Pediatric venosus defects. Heart. 1999; 82:30-33.
Shunt DefectS
Cardiology. Philadelphia: Hanley and Belfus; 1992:513-24. 22. Campbell M. Natural history of atrial septal defect. Br Heart J.
4. Anderson RH, Brown NA, Webb S. Development and structure 1970; 32:820-26.
of the atrial septum. Heart. 2002; 88:104-10. doi:10.1136/ 23. Warnes CA, Williams RG, Bashore TM, Child JS, Connolly
heart.88.1.104. HM, Dearani JA, del Nido P, Fasules JW, Graham TP, Hijazi
5. Hagen PT, Scholz DG, Edward WD. Incidence and size of ZM, Hunt SA, King ME, Landzberg MJ, Miner PD, Radford
patent foramen ovale during the first 10 decades of life: An MJ, Walsh EP, Webb GD, Smith SC Jr, Jacobs AK, Adams CD,
autopsy study of 965 normal hearts. Mayo Clin Proc. 1984; Anderson JL, Antman EM, Buller CD, Creager MA, Ettinger
59:17-20. SM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle
6. Van Mierop LHS. Embryology of the atrioventricular canal BW, Nishimura RA, Page RL, Riegel B, Tarkington LG, Yancy
region and pathogenesis of endocardial cushion defects. In: CW. Atrial septal defect. In: ACC/AHA 2008 guidelines for
Feldt RH, McGoon DC, Ongley PA (Eds). Atrioventricular the management of adults with congenital heart disease. Atrial
Canal Defects. Philadelphia; WB Saunders: 1976:1-12. septal defect. A report of the American College of Cardiology/
7. Weinberg P, Patel A, D’Alessandro L. Anatomy of the atrial American Heart Association Task Force on Practice
septum: transcatheterclosure of ASDs and PFOs. Minneapolis: Guidelines (Writing Committee to Develop Guidelines on the
Cardio text publishing; 2010:3-17. Management of Adults With Congenital Heart Disease). J Am
8. Schott JJ, Benson DW, Basson CT, Congenital heart disease Coll Cardiol. 2008; 52:e173-78.
caused by mutations in the transcription factor NKX2-5. 24. Driscoll, Allen HD, Atkins DL, et al. Guidelines for evaluation
Science. 1998; 281:108-11. and management of common congenital cardiac problems in
9. Benson DW, Sharkey A, Fatkin D, et al. Reduced penetrance, infants, children, and adolescents. A statement for healthcare
variable expressivity, and genetic heterogeneity of familial professionals from the Committee on Congenital Cardiac
atrial septal defects. Circulation. 1998; 97:2043-48. Defects of the Council on Cardiovascular Disease in the Young.
10. Li QY, Newbury-Ecob RA, Terrett JA, et al. Holt-Oram American Heart Association Circulation. 1994; 90:2180-88.
syndrome is caused by mutation in TBX5, a member of the 25. Dennis C, Spreng DS Jr, Nelson GE, et al. Development of
Brachyury (T) gene family. Nat Genet. 1997; 15:21-29. a Pump-oxygenator to Replace the Heart and Lungs: An
11. Bedford DE, Papp C, Parkinson J. Atrial Septal Defect. Brit Apparatus Applicable to Human Patients and Application to
Heart J. 1941;3:37. One Case Ann Surg. 1951; 134:709-21.
12. Cockerham JT, Martin TC, Gutierrez FR, et al. Spontaneous 26. Horvath KA, Burke RP, Collins JJ Jr, et al. Surgical treatment
closure of secundum atrial septal defect in infants and young of adult atrial septal defect: early and long-term results. J Am
children. Am J Card. 1983; 52:1267-71. Coll Cardiol. 1992; 20:1156-59.
13. Radzik D, Davignon A, Van Doesburg N, et al. Predictive 27. Ghosh S, Chatterjee S, Black E, et al. Surgical closure of atrial
factors for spontaneous closure of atrial septal defects septal defects in adults: effect of age at operation on outcome.
diagnosed in the first 3 months of life. J Am Coll Cardiol. Heart. 2002; 88:485-87.
1993; 22:851-53. 28. Jones DA, Radford DJ, Pohlner PG. Outcome following
14. Hanslik A, Pospisil U, Salzer-Muhar U, et al. Predictors surgical closure of secundum atrial septal defect. J Paediatr
of spontaneous closure of isolated secundum atrial septal Child Health. 2001; 37:274-77.
defect in children: a longitudinal study. Pediatrics. 2006; 118: 29. Attenhofer Jost CH, Connolly HM, Danielson GK, et al. Sinus
1560-65. venosus atrial septal defect: long-term postoperative outcome
15. McMahon CJ, Feltes TF, Fraley JK, et al. Natural history of for 115 patients. Circulation. 2005; 112:1953-58.
growth of secundum atrial septal defects and implications for 30. Roos-Hesselink JW, Meijboom FJ, Spitaels SEC. Excellent
transcatheter closure. Heart. 2002; 87:256-59. survival and low incidence of arrhythmias, stroke and heart
16. Craig RJ, Selzer A. Natural history and prognosis of Atrial failure long-term after surgical ASD closure at young age. A
septal defect. Circulation. 1968; 37:805. prospective follow-up study of 21-33 years: Eur Heart J. 2003;
17. Konstantinides S, Geibel A, Olschewski M, et al. A comparison 24:190-97.
of surgical and medical therapy for atrial septal defect in adults. 31. Murphy JG, Gersh BJ, McGoon MD, et al. Long-term outcome
N Engl J Med. 1995; 333:469-73. after surgical repair of isolated atrial septal defect. Follow-up
18. St John Sutton MG, Tajik AJ, McGoon DC. Atrial septal at 27 to 32 years. N Engl J Med. 1990; 323:1645-50.
defect in patients ages 60 years or older: operative results 32. Attie F, Rosas M, Granados N, et al. Surgical treatment for
and long-term postoperative follow-up. Circulation. 1981; secundum atrial septal defects in patients >40 years old. A ran-
64:402-09. domized clinical trial. J Am Coll Cardiol. 2001; 38:2035-42.
19. Berger F, Vogel M, Kramer A, et al. Incidence of atrial flutter/ 33. King TD, Thompson SL, Steiner C, et al. Secundum atrial septal
fibrillation in adults with atrial septal defect before and after defect. Nonoperative closure during cardiac catheterization.
surgery. Thorac Surg. 1999; 68:75-78. JAMA. 1976; 235:2506-09.
20. Steele PM, Fuster V, Cohen M, et al. Isolated atrial septal 34. Du ZD, Hijazi ZM, Kleinman CS. Comparison between
defect with pulmonary vascular obstructive disease: Long-term transcatheter and surgical closure of secundum atrial septal defect
follow-up and prediction of outcome after surgical correction. in children and adults: results of a multicenter nonrandomized
Circulation. 1987; 76:1037-42. trial. J Am Coll Cardiol. 2002; 39:1836-44.
264
35. DiBardino DJ, McElhinney DB, Kaza AK, et al. Analysis
of the US Food and Drug Administration Manufacturer and
37. Knepp MD, Rocchini AP, Lloyd TR, et al. Long-term follow
up of secundum atrial septal defect closure with the Amplatzer
18
User Facility Device Experience database for adverse events septal occluder. Congenit Heart Dis. 2010; 5:32-37.
InteratrIal DefectS
involving Amplatzer septal occluder devices and comparison 38. Al-Anani SJ, Weber H, Hijazi ZM. Atrioventricular block after
with the Society of Thoracic Surgery congenital cardiac transcatheter ASD closure using the Amplatzer septal occluder:
surgery database. J Thorac Cardiovasc Surg. 2009; 137:1334- risk factors and recommendations. Catheter Cardiovasc Interv.
41. 2010; 75:767-72.
36. Jones TK, Latson LA. Multicenter Pivotal Study of the 39. Krumsdorf U, Ostermayer S, Billinger K, et al. Incidence and
HELEX Septal Occluder Investigators, et al. Results of the US clinical course of thrombus formation on atrial septal defect
multicenter pivotal study of the HELEX septal occluder for and patient foramen ovale closure devices in 1,000 consecutive
percutaneous closure of secundum atrial septal defects. J Am patients. J Am Coll Cardiol. 2004; 43:302-09.
Coll Cardiol. 2007; 49:2215-21.
265
http://vip.persianss.ir
C hapter
http://vip.persianss.ir
4 landmarks on its right ventricular aspect.38 The normal 3. Parietal band or distal conal septum (outlet septum).
ventricular septum is mostly muscular with a small fibrous 4. Septal band or proximal conal septum (conoventricular
portion, the membranous septum. septum).
shunt defects
The four regions are the inlet septum, trabecular septum, The atrioventricular node located in the triangle of Koch
outlet or infundibular septum (together making up the (formed by the tendon of Todaro, the coronary sinus ostium
muscular septum), and the membranous septum. and the septal leaflet of the TV) gives rise to the atrioventricular
The inlet septum is smooth walled and extends from the bundle (Bundle of His).40 The atrioventricular septum is itself
septal attachment of the tricuspid valve (TV) to the distal pierced by the atrioventricular bundle as it passes from the
attachments of the tricuspid tensor apparatus. The inlet septum apex of the triangle of Koch to reach the crest of the muscular
separates the septal cusps of the mitral and tricuspid valves. septum.41 At this point, the bundle is on the posteroinferior
The apical trabecular zone separates the coarse trabeculations margin of the membranous septum, which lies just posterior
of the right ventricular from the fine ones seen in the left to the commissure of the septal and anterior leaflets of the
ventricular apical septum. The trabecular portion separates TV. The right bundle branch traverses along the anteroinferior
the body and apices of the two ventricles. It extends from the border of the membranous septum to then enter the right
attachments of the tricuspid leaflets outward to the apex and ventricle (RV). Sometimes in inlet defects, the bundle of His
upwards to the crista supraventricularis. The smooth-walled passes anterosuperiorly to the defect.
outlet or infundibular septum, extends from the crista to the
pulmonary valve. The outlet septum separates the outlets ClaSSIfICatIon
of the ventricles. The supraventricular crest is an extensive
ledge in the muscular zone in the normal heart that separates Many classifications of VSDs have been proposed. Soto et al
the tricuspid from the pulmonary valves and the pulmonary classified VSDs depending on their location in the IVS as seen
from the aortic valves. The three muscular components of from the right ventricular side.38 They are divided into four
the ventricular septum fan out from the small membranous types of defects: 1. Perimembranous, 2. Muscular, 3. Outlet
septum, which lies under the commissure of the anterior and 4. Inlet.
and the septal tricuspid leaflets and below the right and the Anderson et al42 classified the VSDs according to the
noncoronary cusps of the aortic valve. The membranous relation of the defect to the atrioventricular conduction axis,
septum is further divided by the septal leaflet of the TV into i.e.
atrioventricular and interventricular components.38 Schematic i. The membranous septum.
diagram of the location of various types of VSD is given in ii. The relation of the defect to the atrioventricular valves.
Figure 1. iii. The relation of the defect to the arterial valves.
The four main anatomic components that make up the iv. The position of the defect within the ventricular septum,
normal IVS as described by Van Praagh et al39 are as follows: i.e. the inlet, trabecular or outlet part of the septum.
1. Atrioventricular canal septum (inlet septum). They have classified VSDs into four types: perimembra-
2. Muscular septum or ventricular sinus septum (trabecular or nous, muscular defects, doubly committed juxta-arterial and
muscular). juxtatricuspid (non-perimembranous) defects.
anatomical Classification
I. Perimembranous defects (infracristal, subaortic, mem-
branous, conoventricular): They are the most common
and account for 80 percent of all VSDs. These defects
involve the membranous septum with extension into the
adjacent inlet, outlet or muscular septum. They lie in
the outflow tract of the left ventricle (LV), immediately
beneath the aortic valve. There is fibrous continuity be-
tween the aortic and tricuspid valves. The conduction
bundle is always found in the posteroinferior margin of
the defect. In perimembranous VSD, rarely LV to right
atrium (RA) shunt (Gerbode defect) may be seen. Van
Praagh’s classification considers that ‘perimembranous’
is a misnomer for this VSD as ‘peri’ is the Greek pre-
figure 1: Schematic diagram of the anatomical position of various fix meaning ‘around’. They suggest that the appropriate
types of ventricular septal defects. Source: The Lancet, 377 (9771), terminology should be ‘paramembranous’ VSD as the
268 Penny DJ, Vick GW 3rd; Ventricular Septal defect 1103-12 Copyright
(2011), with permission from Elsevier defect lies beside the membranous septum.39
In paramembranous defect, there can be a variable de- Kirklin’s Classification47 19
gree of anterior malalignment between the infundibu-
lar septum and the anterior ventricular septum such Type I: VSDs are termed as supracristal, infundibular,
http://vip.persianss.ir
4 VSDs may be classified into small, moderate and large the pulmonary capillary pressure and there is elevated, but
based on the size of the defect and also based on the subsystemic PVR, which is variable. Therefore, in a large VSD
hemodynamics.2,48,49 both pulmonary arterial and venous pressures are elevated.
shunt defects
http://vip.persianss.ir
4 syndrome. Hence it is very important to know, when and
how the VSDs close spontaneously.
Spontaneous closure occurs frequently in children and
shunt defects
aortIC regurgItatIon
272 figure 4: Transthoracic echocardiography in parasternal long axis
The incidence of aortic cuspal prolapse in outlet VSDs has view shows large vegetation on the right ventricular (RV) side literally
been shown to be as high as 73%. They can progress to AR closing the small VSD. Ao = Aorta; LA = Left atrium; LV = Left ventricle.
19
in 52–78% of the patients. In perimembranous VSDs, aortic postnatal fall, but there is a small risk of increase, usually
cuspal prolapse has been shown to be 14% with progression beyond 20 years of age. In patients with pulmonary artery
to AR in 6%.62 In infancy and early childhood only aortic cusp systolic pressure >50 percent of the systemic arterial systolic
prolapse without AR may be present, but progressive AR may pressure, there is significant risk for the development of
develop. The cause of the aortic cusp prolapse and AR in the pulmonary vascular changes.23 Measured PVR falls to high
doubly committed subarterial VSD is due to the unsupported normal levels in infancy and gradually rises in the ensuing years
right coronary cusp with the combined Venturi effect produced if the defect does not become smaller. The risk of development
by the VSD jet. In early systole, blood is ejected from the of permanent pulmonary vascular disease is very rare before
LV and is also shunted through the VSD. The anatomically the first year of life.66,67 Hence, prompt diagnosis and closure
unsupported coronary cusp and aortic sinus are driven into the of these defects at least prior to 18 months of age is likely to
RV due to the Venturi effect. The Venturi effect is caused by reduce the incidence of development of pulmonary vascular
the high velocity jet passing through the small VSD causing disease. If untreated these large or non-restrictive VSDs will
negative pressure. In diastole the intra-aortic pressure forces have a progressive rise in pulmonary artery pressure and a fall
the aortic valve leaflet to close, but the unsupported cusp in left to right shunting. In turn, eventually this leads to higher
(right or noncoronary) is pushed down into the left ventricular PVR and to Eisenmenger syndrome.
outflow tract away from the opposed coronary cusp, resulting
in AR (Figures 5A to C).63 In perimembranous defects, the InfeCtIVe enDoCarDItIS
AR is more due to the prolapse of the noncoronary cusp. The
AR is mainly as a result of the structural abnormality due to Infective endocarditis (IE) is an uncommon risk occurring in
the maldevelopment of the aortic commissure (between non- <1 to 3 percent of patients with VSD.67,68 A small peri-
coronary and right cusp) and is aggravated by the Venturi membranous VSD that does not close spontaneously is
effect of the VSD jet.64,65 Occasionally, the deformity of the generally associated with a good prognosis, but is at risk for
aortic cusps themselves can cause the AR, this is mostly seen development of IE. The vegetation is usually located on the
with perimembranous defects. septal tricuspid leaflet at the site of impact of the jet. In muscular
VSDs the incidence of IE is low, as the jet is dispersed in the
Subaortic Stenosis RV cavity. The site of the vegetation can occasionally be on
the aneurysm of the ventricular septum. Rarely, an acquired
Patients with membranous VSDs can occasionally develop left ventricular to right atrial shunt, Gerbode defect, can occur
discrete fibrous or fibromuscular subaortic stenosis, which is due to the perforation of the septal tricuspid leaflet secondary
generally progressive and there is potential for damage to the to endocarditis.
aortic valve resulting in AR.
gerboDe DefeCt
pulmonary Vascular obstructive Disease
A Gerbode defect is a rare type of VSD communicating
Pulmonary vascular obstructive disease may develop in 10 between the LV and RA. The LV–RA communications were
percent of the large VSDs. In patients with pulmonary artery first described in the 19th century by Thurman.69 It was not
and RV systolic pressure < 50 percent of the systemic arterial until 1958, however, that interest in this lesion was renewed
systolic pressure there is moderate left to right shunt with following the publication by Gerbode et al. of a series of 273
possible CHF. The PVR does not increase after the initial five patients who underwent successful surgical repair.70
http://vip.persianss.ir
4 The defect is usually congenital, but rarely is acquired. They 3. The third is the combined supravalvular and infravalvular
account for approximately 0.08% of all congenital cardiac defect or also called as Type III.
anomalies.71 Associated abnormalities occur in about 1/3 The physiological consequences of the Gerbode defects
shunt defects
of cases, of which ASD is the most common.72 An acquired depends upon the magnitude of the shunt which is dependent
Gerbode defect has been described following ventricular on the size of the defect and PVR.79 The shunting from the
septal perforation in the setting of bacterial endocarditis,73 LV to RA is predominantly systolic due to the large systolic
trauma,74 myocardial infarction,75 valve replacement76 and gradient between these chambers. The small gradient which
following surgical closure of VSD.77 exists during diastole produces negligible shunting. Smaller
The Gerbode defects result from a defect in the defects result in small size shunts and they can remain
membranous septum. The TV is normally more apically clinically silent. In the presence of large defect, the entire shunt
displaced than the mitral valve. Riemenschneider and Moss72 flow is returned to both ventricles during diastole, causing
classified LV–RA communications into supravalvular biventricular volume overload and enlargement of all four
and infravalvular types (Figure 6). It was based on the chambers. This is contrary to VSDs, where only LV volume
insertion of the septal leaflet of the TV, which divides the overload and in ASDs where RV volume overload occurs.73
membranous septum into atrioventricular (supravalvular) Significant PH can occur, but is not common.
and interventricular (infravalvular) portions. Sakakibara The clinical picture of Gerbode defect varies with mixed
and Konno have classified the LA-RA communications as symptoms related either to the LV to RA shunt or the underlying
Types I, II and III.78 The types of Gerbode defects are: etiology. In small defects, the shunt is well tolerated and there
1. The supravalvular defect, which accounts for 1/3, occurs may be no characteristic symptoms or clinical signs. These
in the atrioventricular septum. The shunt occurs between defects can remain clinically silent. In larger defects there
the LV and RA above the septal leaflet of the TV, which may be significant symptoms like failure to thrive, or exercise
remains intact. It is also called as direct type or Type I. It is intolerance and CHF. Physical findings are similar to VSD
the less common form and is usually acquired, more often with a loud harsh holosystolic murmur often associated with a
due to IE. thrill at the left sternal margin in the fourth or fifth intercostal
2. The more common infravalvular defect, which accounts space.73
for the remaining 2/3, occurs in the interventricular
membranous septum. This shunt produces a communication InVeStIgatIonS
between the two ventricles and the shunted blood entering
the RV is in turn diverted to the RA through associated
electrocardiogram
defects in the TV. There may be a variety of forms of
which septal leaflet perforation(s) are the most common. Electrocardiogram (ECG) is a useful mirror of the physiologic
This defect is found inferior to the insertion of the TV and changes and not the anatomical location of the VSD. The
is also called as indirect type or Type II. size of the VSD, degree of volume overload and PVR can
be predicted by ECG. Small VSDs have normal ECG. The
permembranous VSDs with septal aneurysm have increased
incidence of rhythm and conduction disturbances like atrial
fibrillation, flutter, paroxysmal atrial tachycardia, junctional
rhythm and complete heart block.80
Moderate VSDs have sinus rhythm, PR interval is normal
or slightly prolonged. The axis is usually normal. In about
8 percent of patients, the QRS axis is leftward, superior
and counter clockwise, as in endocardial cushion defects,
regardless of size.81 Inlet VSDs have left axis deviation (LAD),
when there is a component of atrioventricular septal defect.2
In multiple VSDs, 40 percent can have LAD. There can be
broad notched left atrial P waves in L1 and L2 with broad P
terminal force in V1. There is varying degrees of LVH. The tall
R waves may be associated with tall, peaked T waves in L2, L3
and aVF. The leads V5 to V6 show prominent Q waves, tall R
waves and tall, peaked T waves.
In large nonrestrictive VSDs evidence of combined
ventricular hypertrophy is common. This is seen in the mid
figure 6: Schematic diagram showing the anatomic position of
the Gerbode defects. A. Direct or supravalvular type B. Indirect or
precordial leads as large equiphasic RS complexes (> 50 mm),
274 the “Katz-Wachtel phenomenon” (Figure 7). There is usually
infravalvular type. The combined type is a combination of A and B.
19
figure 8: 12 lead ECG shows large equidiphasic RS complex in the midprecordial leads with tall R >18 mm
in V1 in a 12-year-old child with large ventricular septal defect and pulmonary hypertension
right axis deviation. The biventricular hypertrophy is seen as the combination of right atrial P waves with left ventricular
tall ‘R’ wave in lead V1, deep Q waves, tall R and peaked, tall hypertrophy.70,72
‘T’ waves in V5 to V6 (Figure 8). In Eisenmenger complex,
the ‘P’ waves are peaked with right sided axis. There is a tall Chest X-ray
monophasic ‘R’ preceded by small ‘q’ or followed by small ‘s’
wave in V1. In 1913, Vaquez and Bordet described the radiological features
In Gerbode defects there is both biatrial and biventricular of VSD.82 Chest X-ray is practically normal in small VSDs.
enlargement. The tall peaked right atrial P wave in Lead II may Moderate VSDs show cardiac enlargement of varying severity
be present from infancy. There is rSr in V1, and prominent left and increased pulmonary vascular markings (PVM) or plethora
precordial q waves, tall R waves, upright T waves indicating (Figure 9A). The downward and leftward displacement of 275
biventricular volume overload. The hallmark in the ECG is the cardiac silhouette is due to LV enlargement. The PVMs
http://vip.persianss.ir
4
shunt defects
a B c
figures 9a to c: Chest X-ray in posteroanterior view A. shows cardiomegaly with pulmonary plethora in moderate sized ventricular septal
defect (VSD); B.shows huge cardiomegaly with dilatation of the cardiac chambers with plethora in a case of very large VSD with mild pulmonary
hypertension (PH) ; C. shows peripheral pruning with no vascularity seen in lateral 1/3 of the lung fields (multiple arrows) in a case of large VSD
with severe PH, with dilated right atrium and no cardiomegaly
echocardiography
Echocardiography with color Doppler flow evaluation is
widely used to diagnose and provide physiologic information
about the VSD. The color Doppler allows for as small as
2 mm VSDs, not seen on two-dimensional echocardiography,
to be identified. To assess VSD completely, one must not only
localize it, but also define its shape and dimensions (Figure 10),
which is accomplished by viewing the defect from multiple
imaging planes (Figure 11). The standard echocardiographic
views like apical four chamber view, parasternal long axis view,
parasternal short axis view, subcostal sagittal views provide
accurate information about the specific anatomical location of figure 11: Transthoracic echocardiography in inverted apical four
the VSD’s. Apical four chamber view is helpful in diagnosing chamber view shows large perimembranous ventricular septal defect
276
inlet VSD’s, mid muscular and apical muscular defects. trans VSD jet velocity is high with restrictive defects, reflecting 19
Parasternal long axis view demonstrates the perimembranous normal pulmonary and RV systolic pressure. The trans VSD
defects with or without formation of septal aneurysms. gradient of >64 mm of Hg indicates a restrictive VSD with
http://vip.persianss.ir
4 3. To assess PVR and to study reactivity of the elevated PVR
to different pulmonary vasodilators (100% O2 and inhaled
nitric oxide), especially in older patients.
shunt defects
http://vip.persianss.ir
4 have been in vogue for the past 15 years. Although relatively is 4 mm larger and the proximal disc is 3 mm larger than
common, perimembranous VSDs can be difficult to close the diameter of the waist. To achieve immediate complete
percutaneously. Previous devices (e.g. Rashkind or button closure, three Dacron polyester patches are sewn securely
shunt defects
devices) have been unsuccessful in attempts to close these with polyester thread into the two discs and the waist of the
VSDs, because of the proximity of the defects to the aortic device. The device size corresponds to the diameter of the
valve and the potential for aortic valve damage. waist. The mechanism of closure involves stenting of the VSD
Now many varieties of new devices like muscular septal by the device and subsequent thrombus formation within
occluder for muscular VSDs, asymmetrical and symmetrical the device with eventual complete neoendothelialization.
perimembranous septal occluder and Amplatzer duct The device is available in sizes from 6 to 24 mm and these
occluder II (ADO II) are available to close perimembranous are delivered through 6 to 9 French sheaths. The delivery
VSDs and rarely Gerbode shunts. The Amplatzer devices system is prepackaged with a long Mullins type sheath,
(St. Jude Medical, Plymouth, MN) are made up of Nitinol, loader, diaphragm with side arm flush, delivery cable and
an alloy of 55 percent nickel and 45 percent titanium and pin vise. The Amplatzer membranous VSD occluder, is an
this has superelastic properties.98 It also has been proven asymmetric, self-expandable, double-disc device, unlike the
to have excellent biocompatability. The muscular VSD muscular septal occluder. Current recommendations are to
occluder (AVSDO) is a double-disc device. The thickness use this device in older patients, who weigh > 8 kg and who
of the nitinol wire is 0.004″ for devices 10 mm and smaller have a subaortic rim >2 mm. The various types of devices
and 0.005″ for larger devices. The leading retention disc with their characteristics are shown in Figures 16A to E.
a B c
http://vip.persianss.ir
4
shunt defects
a B
figures 17a and B: A. Left ventricular (LV) angiogram in left anterior oblique view shows 8 mm perimembranous ventricular septal defect; B:
Aortic root angiogram in left lateral view shows 10 mm symmetrical, perimembranous VSD device in situ with no aortic regurgitation
a B
282 figures 18a and B: A. Left ventricular (LV) angiogram in left anterior oblique (LAO) view shows a conical shaped ventricular septal defect,
well away from the aortic valve; B. LV angiogram in LAO view shows ADO II in situ with no residual shunt
19
a B
figures 20a and B: A. Left ventricular angiogram in anteroposterior view shows the ventricular septal defect jet opacifying right atrium (RA) in 283
a 10-year-old patient with Gerbode defect; B. Hand injection of contrast given from the side arm of ‘Y’ connecter shows the proper positioning of
ADO II device. Ao = Aorta; LV = Left ventricle; RV = Right ventricle
http://vip.persianss.ir
4
shunt defects
a B
figures 21: Post procedure transthoracic echocardiogram in apical four chamber view with color Doppler shows Amplatzer duct occluder (ADO
II) with two retention skirts (arrow) one in left ventricle (LV) and another in right atrium (RA) with no tricuspid regurgitation or residual shunt in the
infant with Type II Gerbode defect. Note the dilatation of LV and RA due to the Gerbode defect.
a B
figures 22a and B: A. Left ventricular angiogram in postsurgical ventricular septal defect (VSD)
closure patient (sternal suture wires are seen) with residual VSDs, non-compaction of left ventricle with
Swiss cheese VSDs; B. Fluoroscopy in left anterior oblique view shows two ADO II devices (arrows)
in situ
There is not much literature on device closure of large mm Hg and PVRI decreased from 13.8 to 7.7 after 100 percent
midmuscular VSDs with severe PH. The surgery carries high- O2 inhalation. The QP: QS increased from 1.2 to 2:1 after O2
risk in such patients. However in selected cases, akin to flap inhalation and the right to left shunt disappeared, SaO2 increased
surgery, the fenestrations can be done with large dilator prior from 90 to 98 percent. This patient underwent device closure
to deploying the device. A 12-year-old girl had previously with 24 mm VSD muscular septal occluder after 2 fenestrations
undergone PDA ligation 4 years years back. Her aortic pressure were iatrogenically created with 7F dilator (Figures 25A
284 was 110/70 m 83 and pulmonary artery pressure was 92/60 m 71 and B). After deploying the fenestrated device, one can
mm Hg (PCW pressure was 22), which dropped to 76/46 m 56 check with either RV or LV angiogram (Figures 26A and B).
The position of the device and residual shunt can be assessed 19
by either TTE or TEE with color Doppler. On one year follow-
up, the pulmonary artery pressure has dropped to 40 mg Hg on
Hybrid Surgery
Hybrid surgery is a combined surgical and nonsurgical
approach to close MVSDs, especially in infants with low
weight. The transcatheter approach for large MVSDs requires
large introducing sheath. Hence device closure is not feasible
in small infants. Under general anesthesia, hemisternotomy is
figure 23: Fluoroscopy shows atrial and ventricular done with systemic heparinisation. The pericardium is opened.
septal devices in situ Purse string is taken over the anterior surface of the RV. The RV
a B
figures 24a and B: A. Left ventricular angiogram in left anterior oblique view in a 14-year-old boy shows large apical ventricular septal defect
(VSD) with hypertrophied bands in right ventricle (RV), which makes it difficult for closure from the jugular approach; B. As the patient had atrial
septal defect (ASD), the Mullin sheath is passed through ASD into left ventricle and then through the VSD into RV directly. But still the device is
seen in the RV bands
285
http://vip.persianss.ir
4
shunt defects
a B
figures 25a and B: A. Method of creating fenestration in the 24 mm Lifetech muscular septal occluder;
B. Two iatrogenically created fenestrations with 7F dilator seen
a B
figures 26a and B: A. Left ventricular (LV) angiogram in left anterior oblique (LAO) view shows large
midmuscular ventricular septal defect (VSD); B. LV angiogram in LAO view shows 24 mm VSD muscular
device in situ with jet of contrast through the holes. Post-procedure pulmonary artery pressure dropped
from 92/60 m 71 to 76/46 mm 56 mm Hg, oxygen saturation increased from 90 to 98 percent
puncture is done with a 18 gauge needle (modified Seldinger) since it is accomplished on the beating heart. The position of
under TEE guidance. 0.038″ × 95 cm diagnostic guide wire is the device can be checked by both LV angiogram and TEE
introduced through the needle and through the VSD into LV. (Figures 29A and B).
A 10 F sheath is passed over guidewire into LV (Figure 28A).
Through the sheath, the Amplatzer VSD occluder is passed future Direction
and the LV disc deployed in LV and the device is deployed by
releasing the proximal disc in the RV (Figure 28B). The major The interventional treatment of VSD is much more
286 advantage of this procedure is avoidance of cardiopulmonary complicated than closure of secundum ASD or PDA. There
bypass, less blood loss and speedy postoperative recovery, are mitral and tricuspid valve apparatus in both ventricular
19
a B
figures 28a and B: A. 14 mm ventricular septal defect (VSD) muscular septal occluder being introduced in a 9 kg girl; B. Hybrid closure of
VSD. Note: The sternal spreader, the deployed device, the sheath placed through the RV free wall under fluoroscopic and transesophageal
echocardiographic guidance
cavities. There are also moderator and other muscle bands by catheters or guide wires. Therefore, most of the defects
in the right ventricular cavity. The chordae tendinae and targeted for closure are muscular defects, which are at least
papillary muscle of septal leaflet of TV sits on the septum 4 mm away from any cardiac valve. The closure results and
and come in the way of making an arteriovenous loop. safety depends on the device used and also on the location
Perimembranous VSD is usually located in an area quite of the defects. With AVSDO, the complete closure rate is as
near the aortic and tricuspid valves. Encroaching any of these high as 100 percent. Besides, ADO and ADO II are also used 287
structures would cause severe complications. In addition, the in selected cases. ADO II has simple and smaller delivery
position and orientation make the defect, difficult to be passed system and can be effectively repositioned or retrieved
http://vip.persianss.ir
4
shunt defects
a B
figures 29a and B: A 2-year-old girl with 8 mm, midmuscular ventricular septal defect (VSD) closed
with 14 mm Amplatzer muscular VSD through hybrid surgery. The pulmonary artery pressure dropped
from 80/40 to 50/12 mm Hg after hybrid device closure: A. Left ventricular angiogram in left anterior
oblique view; B. Transthoracic echocardiogram in apical four chamber shows device in situ with no
residual shunt
http://vip.persianss.ir
4 46. Hagler DJ, Edwards WD, Seward JB, et al. Standardized no-
menclature of the ventricular septum and ventricular septal
64. Van Praagh R, Mcnamara JJ. Anatomic types of ventricular
septal defect with aortic insufficiency. Diagnostic and surgical
defects, with applications for two-dimensional echocardiog- considerations. Am Heart J. 1968; 75:604-19.
shunt defects
raphy. Mayo Clin Proc. 1985; 60:741-52. 65. Tatsuno K, Konno S, Ando M, et al. Pathogenetic mechanisms
47. Kirklin JW, Harshbarger HG, Donald DE, et al. Surgical of prolapsing aortic valve and aortic regurgitation associated
correction of ventricular septal defect: anatomic and technical with ventricular septal defect. Anatomical, angiographic, and
considerations, J Thorac Surg. 1957; 33:45-59. surgical considerations. Circulation. 1973; 48:1028-37.
48. Gumbiner CH, Takao A. Ventricular septal defect. In: Garson 66. Nadas AS, Ellison RC, Weidman WH. Pulmonary stenosis,
A Jr, Bricker JT, Fisher DJ, Neish SR (Eds). The Science aortic stenosis, ventricular septal defect: clinical course and
and Practice of Pediatric Cardiology. Williams and Wilkins indirect assessment. Circulation. 1977; 56:(Suppl 1-1).
Baltimore, Md; 1998. pp. 1119-40. 67. van Hare GF, Soffer LJ, Sivakoff MC, et al. Twenty-five-
49. Specific cardiac defects. In Libby: Braunwald’s Heart Disease: year experience with ventricular septal defect in infants and
A Textbook of Cardiovascular Medicine, 8th edition. Libby children. Am Heart J. 1987; 114:606-14.
P, Bonow RO, Mann DL, Zipes DP (Eds). Elsevier Saunders 68. Kidd L, Driscoll DJ, Gersony WM, et al. Second natural
2007. history study of congenital heart defects. Results of treatment
50. Ellis JH 4th, Moodie DS, Sterba R, et al. Ventricular septal of patients with ventricular septal defects. Circulation. 1993;
defect in the adult: Natural history and unnatural history. Am 87:138-51.
Heart J. 1987; 114:115-20. 69. Thurman J. Aneurysms of the heart. Med Clin Trans R Med
51. Farru O, Duffau G, Rodriguez R. Auscultatory and phonocardio- Clin Soc (Lond) 1838; 21:187.
graphic characteristics of supracristal ventricular septal defect. 70. Gerbode F, Hultgren H, Melrose D, Osborn J. Syndrome of
Br Heart J. 1971; 33:238-45. left ventricular-right atrial shunt: successful surgical repair of
52. French H. Possibility of loud congenital heart murmur disappear- defect in 5 cases, with observations of bradycardia on closure.
ing when child grows up. Guys Hospital Reports. 1918; 32:87. Ann Surg 1958; 148:433-46.
53. Weber FP. Can the clinical manifestation of congenital heart 71. Laurichesse J, Ferrane J, Scebat L, et al. Communication
disease disappear with the general growth and development between the left ventricle and the right auricle. Arch Mal Coeur
of the patient? British Journal of Children’s Diseases. 1918; 1964; 57:703-24.
15:113. 72. Riemenschneider TA Moss AJ. Left ventricular–right atrial
54. Syamasundar Rao P. Diagnosis and management of acyanotic communication. Am J Cardiol 1967; 19:710-8.
heart disease: part II - left-to-right shunt lesions. Indian J 73. Wasserman SM, Fann JI, Atwood JE, Burdon TA, Fadel
Pediatr. 2005; 72:503-12. BM. Acquired left ventricular-right atrial communication:
55. Lin MH, Wang NK, Hung KL, et al. Spontaneous closure of Gerbode-type defect. Echocardiography 2002; 19:67-72.
ventricular septal defects in the first year of life. J Formos Med 74. Olsovsky MR, Topaz O, DiSciascio G, Vetrovec GW. Acute
Assoc. 2001; 100:539-42. traumatic ventricular septal rupture. Am Heart J 1996;
56. Hiraishi S, Agata Y, Nowatari M, et al. Incidence and natural 131:1039-41.
course of trabecular ventricular septal defect: two dimensional 75. Newman JN Jr, Rozanski L, Kreulen T. Acquired left ventricular
echocardiography and color Doppler flow imaging study. J to right atrial intracardiac shunt after myocardial infarction: a
Pediatr. 1992; 120:409-15. case report and review of the literature. J Am Soc Echocardiogr
57. Alpert BS, Mellits ED, Rowe RD. Spontaneous closure of 1996; 9:716-20.
small ventricular septal defects: probability rates in the first 76. Katz ES, Tunick PA, Kronzon I. To-and-fro left ventricular-
five years of life. Am J Dis Child. 1973; 125:194-6. to right atrial shunting after valve replacement shown by
58. Collins G, Calder L, Rose V, et al. Ventricular septal defect: transesophageal echocardiography. Am Heart J 1991; 121:
clinical and hemodynamic changes in the first five years of life. 211-4.
Am Heart J. 1972; 84:695-705. 77. Kudo T, Ryo S, Shimakura T, Imamura E, Imai Y. LV-RA
59. Weidman WH, Blount SG Jr, DuShane JW, et al. Clinical shunt developing after repair of VSD. Kyobu Geka 1974;
course in ventricular septal defect. Circulation. 1977; 56 27:93-8.
(1 Suppl):156-169. 78. Sakakibara S, Konno S. Left Ventricular-Right Atrial
60. Corone P, Doyon F, Gaudeau S, et al. Natural history of Communication. Ann Surg. 1963; 158:93-9.
ventricular septal defect. A study involving 790 cases. 79. Silbiger JJ, Kamran M, Handwerker S, Kumar N,
Circulation. 1977; 55:908-15. Marcali M. The Gerbode defect: left ventricular to right
61. Gasul BM, Dillon RF, Vrla V, et al. Ventricular septal defects; atrial communication-anatomic, hemodynamic, and
their natural transformation into the cyanotic or noncyanotic echocardiographic features. Echocardiography. 2009; 26:
type of tetralogy of Fallot. J Am Med Assoc. 1957; 164: 993-8.
847-53. 80. Thery C, Lekieffre J, Dupuis C. Atrioventricular block
62. Saleeb SF, Solowiejczyk DE, Glickstein JS, Korsin R, Gersony secondary to a congenital aneurysm of the membranous
WM, Hsu DT. Frequency of development of aortic cuspal septum. Histological examination of conduction system. Br
prolapse and aortic regurgitation in patients with subaortic Heart J. 1975; 37:1097-100.
ventricular septal defect diagnosed at < 1 year of age. Am J 81. Gersony WM, Nugent EW, Weidman WH, et al. Report from
Cardiol. 2007; 99:1588-92. the Joint Study on the Natural History of Congenital Heart
63. Ando M, Takao A. Pathological anatomy of ventricular septal Disease. Circulation. 1977(Suppl 1):24.
290 defect associated with aortic valve prolapse and regurgitation. 82. Vaquez H, Bordet E. Le Coeur et al.’Aorte, Etudes Radio-
Heart Vessels. 1986; 2:117-26. graphiques. Paris, JB Bailliere et Fils. 1913.
83. Dzwonczyk T, Davidson WR, Jr. The spectrum of left
ventricular-right atrial communications in the adult: Essentials
92. Kimball TR, Daniels SR, Meyer RA, et al. Effect of digoxin on
contractility and symptoms in infants with a large ventricular
19
of echocardiographic assessment. J Am Soc Echocardiogr septal defect. Am J Cardiol. 1991; 68:1377-82.
291
http://vip.persianss.ir
C hapter
InCIDenCe
Incidence of AVSD varies from 1.4 to 10.8 percent (4–5%)
in some studies of congenital heart disease (CHD). These
constitute 0.19 per 1,000 live birth (New England Regional
Infant Cardiac Program). Prevalence of 0.362 was seen in the
Baltimore Washington Infant Cardiac study. Prevalence of
0.203 using invasive method for diagnosis and 0.242 using
Figure 1: Subcostal short-axis view at the level of the common AV
non-invasive method (Alberta heritage study). The incidence
valve showing the components of the common AV valve. Ao = Aorta;
IBL = Inferior bridging leaflet; LV = Left ventricle; PA = Pulmonary of CHD in offspring of female with AVSD is 9.6 to 14.3
artery; RV = Right ventricle; SBL = Superior bridging leaflet. percent.
20
A B c D
Figures 5A to D: Schematic diagram showing the various types of atrioventricular septal defects. LA = Left atrium; LPV = Left pulmonary vein;
LV = Left ventricle; RA = Right atrium; RPV = Right pulmonary Vein: RV = Right ventricle.
http://vip.persianss.ir
4
Shunt DeFectS
A B c
Figures 6A to c: Schematic diagram of atrioventricular septal defects showing the level of shunting;
A. Both atrial and ventricular shunting; B. Atrial shunting only; C. Ventricular shunting only. LA = Left atrium; LV = Left ventricle;
RA = Right atrium; RV = Right ventricle. Reproduced from Atrioventricular septal defect: from fetus to adult. Craig B.Heart.
2006;92:1879-85, with permission from BMJ Publishing Group Ltd.
A B
Figures 7A and B: Apical four-chamber with color flow mapping in a child with partial atrioventricular septal defect showing, common
atrioventricular junction and small inlet ventricular septal defect with left-to-right shunt. Ventricular septal defect is small due to the attachment
of superior bridging leaflet to crest of ventricular septum (arrow). LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle.
of AVSD is directed towards midportion of ventricular • Interatrial shunt only (primum ASD)
septum. The isolated cleft in the AML is directed towards • Interventricular shunt only (AV canal VSD) (Figures 7A
aortic valve annulus. and B)
• AVSD with intact interatrial and interventricular septum.
Classification II Rarely with complete AVSD, there will be absence of any
interatrial shunt when the superior bridging leaflet is attached to
Rarely AVSD is classified depending on level of shunting of the the lower end of atrial septum and absence of VSD when it is
294 blood in the cardiac chambers (Figures 6A to C): firmly attached to the ventricular septum as described with partial
• Interatrial and interventricular shunts AVSD.
20
A B
Figures 9A and B: Apical four-chamber view with A. Schematic diagram; B. Echocardiography
showing unbalanced atrioventricular septal defect with left ventricular dominance. LA = Left atrium;
LV = Left ventricle; RA = Right atrium; RV = Right ventricle.
Classification III • Unbalanced with left dominant type (Figures 9A and B): It
This type of classification depending upon the size of the is usually associated with pulmonary stenosis/pulmonary
ventricular chambers has practical importance as it helps in atresia.
deciding the modality of treatment for AVSD (univentricular The decision between balanced and unbalanced ventricles
versus biventricular pathway). in borderline cases is best done using AV valve index (AVVI).
• Balanced type
• Unbalanced AVSD: Unbalance in AVSD refers to two Method
distinct but related anatomical features:
1. Ventricular hypoplasia. Tracing the circumference of the common AV valve orifice
2. Malalignment of the AV valve junction. Latter may during end-diastole, averaged over three cardiac cycles using
affect ventricular size developmentally. a subcostal view on 2D echocardiography. This circumference
• Unbalanced with right dominant type (Figures 8A and is then divided by a line drawn over the place of intact
B): This is the common type, usually associated with arch ventricular septum (IVS) from the tip of the infundibuluar 295
hypoplasia, coarctation of aorta. septum to the crest of the muscular septum, thus dividing AV
http://vip.persianss.ir
4
Shunt DeFectS
A B
Figures 10A and B: Assessment of balanced AV septal defect using the image in Figure 1. Tracing circumference of the common AV valve
orifice during end-diastole, averaged over three cardiac cycles using a subcostal view on 2D echocardiography. This circumference is then
divided by a line drawn over the place of IVS from the tip of the infundibuluar septum to the crest of the muscular septum, thus dividing AV valve
into left and right components. The AVVI is expressed as the smaller AV valve area over the larger AV valve area. For a balanced AVSD (Area I
and Area II in Figure) should be between 0.4 and 0.6
A B c
Figures 11A to c: Subcostal short-axis view at the level of AV valves showing the Rastelli classification:
A. Type A; B. Type B; C. Type C patterns of AV valves
valve into left and right components. For a balanced AVVI Classification IV/Rastelli Classification
should be between 0.4 and 0.6 (Figures 10A and B).
When the right-sided component is small, the right ventricle It is more of historical importance. Complete AVSD is divided
is hypoplastic, the tricuspid valve overrides a malaligned inlet into type A, B, C based on extent of straddling of anterior
ventricular septum and the right AV valve has attachments that bridging leaflet into right ventricle (RV) (Figures 11A to C).
straddle the VSD. When the left-sided component is small, • Type A: It is seen in 50 to 70 percent of patients. Anterior
296 the morphological left ventricle is hypoplastic, but straddling bridging leaflet (ABL) is completely committed to left
does not occur despite AV malalignment because straddling is ventricle and there is minimal bridging of leaflet into
reserved for conoventricular malalignment. RV. Chordae are attached to the crest of the ventricle.
This type is the most common type associated with of the superior and inferior endocardial cushions. Complete 20
Down’s syndrome. AVSD: Lack of fusion between the superior and inferior
• Type B: More bridging of ABL into RV and chordae are cushions resulting in the formation of separate anterior and
http://vip.persianss.ir
4
Shunt DeFectS
A B
c D
Figures 12A to D: Fetal echocardiogram demonstrating cases of AVSD: A. Balanced AVSD diagnosed in a 19 weeks fetal echocardiogram;
B. Fetal echocardiogram showing four-chamber view with moderate AV regurgitation; C. Fetal echocardiogram in a 18 weeks old showed
unbalanced AVSD; D. Four-chamber view demonstrates shunting across the ASD and VSD components of a case of AVSD. LA = Left atrium;
LV = Left ventricle; RA = Right atrium; RV = Right ventricle.
Figure 13: 12-lead ECG of a 3-year-old patient of AVSD showing qRS axis of –30 degrees (left-axis deviation). Normal P
axis. Right ventricular hypertrophy. Note: The superiorly oriented frontal qRS axis is manifested by dominant S waves in
299
leads III and aVF and prominent R wave in aVR and counter clockwise depolarization results in q waves in I and aVL
http://vip.persianss.ir
4 Various views may be used for defining various
Box 1: Two-dimensional echocardiographic findings
echocardiographic features common to AVSD (Box 1).
common to AvSD patients
Subcostal coronal view shows common AV junction, loss of
Shunt DeFectS
ASSoCIAtIon
There is a strong association of AVSD with trisomy 21. Nearly
30-50 percent of patients with AVSD have trisomy 21. 40 to
45 percent of patients with Down’s syndrome have CHD and
amongst these 40 percent have a AVSD (40% rule). Complete
AVSD also occur in patients with hetrotaxy syndrome (more
common in patients with asplenia than polysplenia). Common
atrium has been associated with Ellis Van Creveld syndrome.
Figure 16: Subcostal sagittal view with color flow mapping from a child The presentation of the defect ranges from fetal life to those
with partial atrioventricular septal defect showing left atrioventricular with partial forms presenting even in later age group.
valve regurgitation through cleft (arrow). LV = Left ventricle; RV = Right
ventricle; TOF (occurring in 6% of patients), DORV (occurring in
6% of patients), malposed great vessels (occurring in 3%
of patients) are frequently associated with complete AVSD
Right Ventricular outflow tract obstruction especially in setting of isomerism. With unbalanced AV
connection leading to hypoplastic left ventricle, aortic arch
Pulmonary stenosis can occur at subvalvular (malalignment should be well profiled in suprasternal long axis view to rule
of outlet septum, infundibular hypertrophy), valvar or sup- out arch anomalies like coarctation of aorta and aortic arch 301
ravalvular levels and can also be well profiled on echocardio- interruption. With hypoplastic RV, pulmonary stenosis and
graphy. pulmonary atresia may be the associations.
http://vip.persianss.ir
4 CARDIAC CAtHeteRIzAtIon AnD AngIogRApHy
As discussed, preoperative assessment can now generally
Shunt DeFectS
http://vip.persianss.ir
4 Box 4: permutation of these strategies results in at
Left atrioventricular valve stenosis: It can result from
excessive suture closure of cleft, congenital anomaly of
least eight possible combination of techniques
AV valve or inappropriate surgical division of common
Shunt DeFectS
1. Using one patch and cutting the bridging leaflets. atrioventricular valve between the two ventricles. Doppler
2. Using one patch, but leaving the bridging leaflets intact,this
is only possible with minimal bridging of both bridging echocardiography helps in assessment of severity and need
leaflets and constitutes a numerically minor subset. for reintervention.
3. Using one patch in which a cut is made to accommodate Right atrioventricular valve stenosis or regurgitation: It is
one of the bridging leaflets, this is applicable when one of less common and has less serious hemodynamic consequences
the bridging leaflets bridge minimally, as in the Rastelli A than left AV valve regurgitation. It can be accurately diagnosed
malformation.
by careful Doppler evaluation.
4. Using one patch, having sutured the bridging leaflets
directly to the ventricular septal crest.
5. Using two patches and attaching the inferior bridging Left Ventricular Outflow Tract Obstruction
leaflet to the ventricular septal crest, while inserting a patch
between the septal crest and the superior bridging leaflet, Subaortic stenosis occurs more frequently after repair of the
which is left intact. partial AVSD. Underlying mechanisms producing stenosis
6. Using two patches, attaching the inferior bridging leaflet
to the ventricular septal crest, while cutting the superior
include, adherence of anterior bridging leaflet to the crest of
bridging leaflet. ventricular septum, membranes or chordae crossing LVOT or
7. Using two patches and cutting the bridging leaflets. redundant atrioventricular valve tissue protruding into LVOT.
8. Using two patches, leaving the bridging leaflets intact. Echocardiography helps in identifying the cause and severity
of obstruction.
which in the setting of the left valve is usually committed postoperative management
to a inferomural or superomural papillary muscle and most
significantly, is usually not regurgitant. Any annuloplasty will After the operation, the patient is kept intubated and ventilated
reduce even further the effective area of the valvar orifice. If until the hemodynamic situation is stable. Because of the
possible, these extra orifices are best left alone. known tendency of these postoperative patients to develop
pulmonary hypertensive crises, it is wise to prevent acidosis
Intraoperative Assessment and to avoid other precipitating factors, such as overly vigorous
intratracheal suction. Monitoring of pulmonary arterial
Because of the complexity of the repair, echocardiographic pressure is advantageous in patients known to have pulmonary
assessment in the immediate postoperative period and in long hypertension. The presence of a conspicuous left atrial ‘v’
term is mandatory to detect any important imperfections in the wave on left atrial pressure tracing, both before and after the
repair. Following lesions should be sought for in the patients procedure, is a good indication for regurgitation. The absence
following AVSD repair. of a ‘v’ wave, unfortunately, is not a fool proof indicator that
the valve will be competent immediately after repair, possibly
Residual Atrial or Ventricular Septal Defects because of the altered hemodynamics due to anesthesia or
through the damping effect of a large atrium. Presence of
Doppler color flow mapping is particularly useful as a rapid substantial ‘v’ waves, nonetheless, is an indication for further
screening technique for residual septal defects and to look for investigation and usually, further attempts at repair of the valve.
their location, size and hemodynamic impact.
ReSultS of SuRgICAl RepAIR
Inadequate Repair of Common Atrioventricular Valve
The function of the left AV valve, ventricular imbalance and
Inadequate repair of common atrioventricular valve is by far pulmonary hypertension are the sole incremental surgical risk
the most common postoperative problem. This will result in factors for death. Results of surgical repair have improved
left/right AV valve regurgitation or left/right AV valve stenosis. steadily over the decades, concomitant with developments
Left atrioventricular valve regurgitation: This is more in medical therapy, more appropriate criteria for selection
common in patients with complete form of AVSD than partial. and improvements in myocardial preservation, surgical skill
Most commonly it occurs at the commissure between anterior and postoperative care. The function of the left AV valve has
and posterior bridging leaflets—cleft mitral valve. Large determined the operative result, in both the short and the long
mural leaflet is also more common in patients with significant term. Late reoperations for left AV valvar dysfunction have been
residual left AV valve regurgitation. Echocardiography helps a source of considerable morbidity and indeed also mortality.
in assessment of severity of regurgitation and its hemodynamic At least 25 percent of patients require reoperation, most
304 significance. commonly because of progressive left AV valve regurgitation
or for relief of LVOTO. The results published to date include bridging of both inferior and superior leaflets, rather than one or 20
the follow-up over a period of 43 years of surgical corrections both leaflets being committed primarily to the LV, is more usual
between 1958 and 2000 of 133 patients with shunting in children with trisomy 21. Accordingly, the angle of the zone
http://vip.persianss.ir
4 SuggeSteD ReADIngS 11. Reeder GS, Danielson GK, Seward JB, et al. Fixed subaortic
stenosis in atrioventricular canal defect: a Doppler
1. Anderson RH, Ho SY, Falcao S, et al. The diagnostic features echocardiographic study. J Am Coll Cardiol. 1992;20:
Shunt DeFectS
306
C hapter
http://vip.persianss.ir
4 EMBrYoLoGY A decreased incidence of PDA is seen in those neonates
whose mothers received prenatal steroids at least 24 hours
The ductus arteriosus is derived from the sixth aortic arch. In before delivery or who had prolonged rupture of membranes
Shunt DefectS
human beings, it develops by about the 6th week of embryonic of more than 72 hours duration. Decreased incidence is
development from the distal portion of one of the sixth paired also seen in neonates with intrauterine growth restriction.42
aortic arches.25 The left, right or both ductus can sometimes Antenatal steroids inhibit PG production and increase the
persist.26,27 The proximal portion of the sixth pair of embryonic responsiveness of the ductus to the constricting effect of
aortic arches usually persist as the proximal branch pulmonary oxygen and decrease its sensitivity to the dilating effects of
arteries and the distal portion of the left sixth arch persists as prostaglandins.42
the ductus arteriosus. In the typical left aortic arch, the aortic Most cases of PDA are sporadic and many are believed to
end of the ductus arteriosus arises distal to the origin of the be due to multifactorial inheritance.43 The recurrence rates
left subclavian artery and inserts at the junction of the main are between 1 to 5 percent among siblings of individuals with
and left pulmonary arteries. The distal right sixth aortic arch isolated PDA.44-48 The mechanism of the genetic inheritance
loses its connection to the dorsal aorta and degenerates. This is not yet known. It occurs with increased frequency in
transformation is complete by 8 weeks of fetal life.28 In the several genetic syndromes with chromosomal abnormalities
fetus, the ductus is about the same diameter as the descending such as trisomy 21 and 18, deletion syndromes 4q, 16p13.3
aorta and at term this is about 10 mm.29 The ductus arteriosus (Rubinstein-Taybi) and 9p (CHARGE), single-gene mutations
usually is functionally closed within 48 hours of birth in full- (such as Carpenter’s syndrome and Holt-Oram syndrome)
term neonates and is considered abnormal if it is patent in and X-linked mutations (such as incontinentia pigmenti).28,49
full-term infants older than 3 months.1,30 The major factors Familial patent arterial ductus can be either isolated or part
influencing its closure after birth are the increased production of a syndrome like Char syndrome, familial thoracic aortic
of local vasoconstrictors (like endothelin) in response to higher aneurysm/dissection and with bicuspid aortic valve with hand
arterial oxygen tension. Also the levels of the vasodilators, anomalies.49
PGE2 and PGI2 (prostacyclin), fall due to the metabolism in A number of teratogens are known to influence the develop-
the now functioning lungs and elimination of the placental ment of the ductus, including rubella, alcohol, amphetamines,
source.28 anticonvulsants like hydantoin and valproate. The ductus is
most sensitive from 18 to 60 days of gestation.50,51 Rubella in-
InCIDEnCE fection, especially in the first 4 weeks of gestation, has a high
occurrence of PDA. The incidence in these rubella affected in-
Isolated PDA accounts for 9 to 12 percent of all CHDs with fants is as high as 85 percent, when associated with other cardi-
a higher incidence in females, with a female to male ratio of ac defects and is about 50 percent when it occurs as an isolated
2 : 1.31,32 The estimated incidence of isolated PDA is 1 in lesion.52,53
2,500 to 1 in 5,000 live births.33-35 If all children with PDA
including those with ‘silent PDA’ (only echocardiographic AnAtoMY
Doppler evidence) are included, then the incidence has been
estimated to be as high as 1 in 500 or 0.1 to 0.2 percent of the In a patient with a normal left-sided aortic arch, the PDA
population.36 connects the main pulmonary artery near the origin of the left
pulmonary artery (LPA) with the descending aorta, 5 to 10 mm
EtIoLoGY distal to the origin of the left subclavian artery. The anatomy
is more varied in the presence of a right-sided aortic arch. In
In premature infants, the PDA is due to immaturity rather the neonatal period, the size and shape varies greatly from
than a developmental anomaly. In the premature neonate, case to case. The PDA is most commonly left sided and is less
the occurrence of PDA is inversely related to the gestational frequently right sided and arises distal to the right subclavian
age and maturity. The incidence is 8 per 1,000 live births artery and inserts near the proximal right pulmonary artery. In
and ranges from 20 to 42 percent.37,38 In preterm neonates, rare instances, there is a bilateral PDA.54 The right-sided PDA
weighing less than 1,000 g, the incidence can be as high as is especially associated with aortic arch anomalies.55-57
80 percent.39 The patency of the ductus after birth in preterm The proper knowledge of anatomy is needed for the cardiac
babies is due to the fact that the immature ductal tissue is surgeon doing the surgical ligation. The PDA passes from the
less sensitive to oxygen-mediated constriction and more anterior aspect of the pulmonary artery to the posterior aspect
sensitive to PG-mediated vasodilation.40 The incidence of the aorta (Figure 1). The anatomic marker of the ductus is
of PDA is higher in neonates with persistent low oxygen the recurrent laryngeal nerve, which typically arises from the
tension in the blood like respiratory distress syndrome, vagus nerve just anterior and caudal to the ductus and loops
acute intrapartum stress, asphyxia and in those born at high posteriorly around the ductus to ascend behind the aorta en
308 altitudes.41 route to the larynx. It is the most commonly injured anatomic
21
http://vip.persianss.ir
4 may be narrow at the aortic insertion. The type C or tubular end of the ductus; it may remain incomplete and dilated at the
type of PDA is tubular without any constriction. The type D or aortic end and is known as ductus ampulla or ‘ductus bump’.
complex type of PDA has multiple constrictions. The type E or The histopathology of a normal ductus, not yet closed and
Shunt DefectS
elongated type of PDA has a bizarre shape with an elongated a persistently patent ductus is different, thus suggesting a
conical appearance and the constriction being remote from primary anomaly and not a secondary effect.68,69 The ductus
the anterior border of the trachea. Within the types A and is a muscular artery with a thicker intima, less elastic tissue,
B, it is further classified into three subgroups depending on spirally arranged smooth muscle fibers and more hyaluronic
the relationship of the site of insertion of the PDA at the acid than the adjacent pulmonary trunk and aorta. The media
pulmonary end to the tracheal shadow.62 of the other arteries is composed mainly of circumferentially
arranged elastic fibers.68-70
Abnormal Anatomy The mechanism of ductal closure involves a complex
interaction of the level of arterial oxygen, circulating PGs,
In the presence of complex CHD, the usual anatomy of the genetic predetermination and unknown factors.71 The rise in
ductus may not be present. In the duct dependant cyanotic systemic oxygen saturation with the onset of ventilation, after
CHDs, the ductus is markedly varied with regards to its birth, causes active constriction in the ductus. Simultaneously,
origin from the aorta, size and shape, length, tortuosity and its there is a decrease in the level of circulating PGs due to
insertion onto the pulmonary artery.63 There are four groups both factors, i.e. reduced production following removal of
seen.64 In the first group A, the PDA arises from the proximal the placenta and increased metabolism in the pulmonary
descending aorta and resembles Krichenko type A PDA. It circulation resulting from the increase in pulmonary flow.
is seen in pulmonary atresia with intact ventricular septum Removal of the strong vasodilatory effect of the PGs promotes
(PAIVS), critical pulmonary stenosis (PS) and tricuspid further constriction of the ductus.72,73 Other vasoactive
atresia. In the second group B, the PDA arises from the substances (such as acetylcholine, bradykinin and endogenous
proximal or middle part of the aortic arch (‘vertical’ ductus catecholamines or variations in pH) may be involved in this
arteriosus). These ducts are most commonly seen in tetralogy dynamic process of ductus closure.72-75 Response to PGs and
of Fallot-pulmonary atresia (TOF-PA), transposition of great oxygen varies with ductal maturity: in the full-term infant the
vessels, ventricular septal defect (VSD) with pulmonary ductus is sensitive to oxygen, while in the premature infant
atresia and in single-ventricle physiology. In the third group the PGs have a dominant effect. Consequently, in premature
C, there is intermediate origin of the PDA. The PDA arises infants failure of ductal closure results from incomplete ductal
more proximally than those in group A, but not as extreme development, whereas in full-term infants, PDA results from
as seen in group B. PDA arises from the opposite side of structural abnormalities of ductal tissue.
the origin of the left subclavian artery (LSCA). In the fourth
group D, the PDA arises from the subclavian artery. It is the HEMoDYnAMICS
least common type, comprising less than 5 percent and this
PDA has the peculiar appearance of a Blalock-Taussig (BT) The persistent patency of the ductus causes left-to-right
shunt. The long tubular ductus arises from the LSCA (or from shunting of the high aortic pressure blood into the low-
the right subclavian artery in a right aortic arch) and joins the pressure pulmonary artery, in both systole and diastole.
pulmonary artery in a roughly perpendicular fashion.64 The magnitude of the left-to-right shunt in the PDA
depends on:76,77
MECHAnISM of DuCtAL CLoSurE 1. The size and length of the PDA (directly proportional to the
diameter, inversely proportional to the length).This governs
As soon as the baby is born and starts crying and taking breath, the resistance offered to flow. In a small or restrictive PDA,
the collapsed lungs expand and the pulmonary circulation the magnitude of the left-to-right shunt is determined by
starts functioning. The ductus arteriosus, which was essential the resistance offered by the ductus.
for fetal circulation, starts closing. The postnatal closure 2. The ratio between the systemic vascular resistance (SVR)
of the ductus occurs in two stages. In the first stage within and the pulmonary vascular resistance (PVR). The pressure
12 to 15 hours after birth (in full-term infants), there is difference between the aorta and the pulmonary artery
contraction of the medial smooth muscle in the wall of the is dynamic and is dependent on the SVR, PVR and the
ductus, which leads to shortening and increased wall thickness. cardiac output. In a large PDA, the magnitude of shunting
There is also protrusion of the intimal cushions into the lumen is determined by the relationship of the SVR and PVR.
and all this results in functional closure.65,66 In the second stage, Hence, the left-to-right shunting through PDA has been
2 to 3 weeks after birth, there is infolding of the endothelium defined as dependent shunting.77
with necrosis and proliferation of subintimal layers which leads In the early weeks of life in term infants, significant
to fibrosis and permanent sealing of the lumen to produce the shunting is unusual because a high PVR limits the
310 ligamentum arteriosum.67 Closure begins at the pulmonary development of a large aorto-pulmonary pressure gradient.78
After a few weeks, volume overload of the left heart develops activity and circulating catecholamines.28 These mechanisms 21
with chamber enlargement as seen in VSD. Therefore, the are responsible for the rapid heart rate and sweating often seen
onset of congestive heart failure (CHF) with PDA is similar in infants with heart failure. The diastolic ‘runoff’ through
http://vip.persianss.ir
4 healthy, but report exercise intolerance or carry the diagnosis incidentally discovered ‘silent’ PDAs have normal cardiac
of asthma. The clinical course of prematures is different from examination.
that in full-term born babies. An untreated large PDA can also produce pulmonary
Shunt DefectS
http://vip.persianss.ir
4 The greatest value of TTE and Doppler evaluation in the (approximately Qp : Qs > 2) and this had more than 90 percent
diagnosis of PDA is to exclude other significant intracardiac specificity and sensitivity.101
lesions.
Shunt DefectS
In a patient with moderate to large PDA, the LA and LV Magnetic resonance Imaging and
are enlarged, while in a small PDA chamber sizes are usually Computed tomography
normal. The ratio of the LA size to the aortic root size (both
measured in systole) can be used to estimate the degree of Computed tomography (CT) can assess the degree of
ductal shunting. If this ratio is greater than 1.2 (normal is 0.8– calcification in adults.102 Volume rendered (VR) CT image
1.0), it suggests a significant shunt.94 can define the anatomy of the PDA well (Figure 6). Magnetic
Doppler echocardiography reveals continuous flow from resonance imaging and computed tomography is used to
the aorta into the MPA. If the magnitude of the left-to-right define anatomy in a PDA with unusual geometry and with
shunt is large, continuous flow around the aortic arch into associated abnormalities of the aortic arch.103 Cardiac
the ductus arteriosus in diastole and flow reversal in the magnetic resonance imaging may be useful to evaluate the
descending aorta are evident.98 There may be also variable anatomy, if a ductus arteriosus aneurysm is suspected.104
levels of continuous flow in the branch pulmonary arteries
related to the magnitude of shunt. As the shunt magnitude nAturAL HIStorY
increases, increased flow in the pulmonary veins is evident.
Color Doppler is a very sensitive modality in detecting the The functional closure of the PDA occurs in 20 percent of the
presence of PDA and is used to estimate the degree of ductal term infants at 24 hours after birth, 82 percent at 48 hours and
shunting. Color flow signal can detect an extremely tiny 100 percent by 96 hours of life.105 The term ‘winking ductus’
patent ductus entering the PA near the origin of the LPA. In a was coined in a study that showed that in healthy newborns
patient with large PDA with PH, with low velocity or right-to- up to day 5, there could be intermittent shunting even when
left flow, it may be difficult to demonstrate even a large PDA. the PDA seems to have closed.106 Even after functional
Associated findings such as septal flattening, unexplained ductal closure, the potential to reopen exists for the next 7 or
RVH and high-velocity pulmonary regurgitation should make
one investigate for a PDA.28 Contrast echocardiography may
be helpful and the microbubbles are seen in the descending
aorta (from ductal right-to-left shunting) and not in the
ascending aorta. The RV pressure can be estimated from the
peak velocity of the tricuspid regurgitation jet. The Doppler
velocity of the pulmonary regurgitation flow, if present, can
be used to estimate the pulmonary artery diastolic pressure.
http://vip.persianss.ir
4 Preterm Infants symptomatic or give targeted presymptomatic or prophylactic
treatment. None of these approaches has shown unequivocal
Treatment of PDA in preterms varies with the magnitude of benefits in terms of outcomes.128
Shunt DefectS
http://vip.persianss.ir
4
Shunt DefectS
a B
c D
figures 7a to D: A. Patent ductus arteriosus (PDA) coil; B. Post procedure echocardiogram showing PDA coil in situ; C. Lateral angiogram
showing type D PDA; D. Post procedure angiogram showing coil in situ with no residual shunt. Ao = Aorta; MPA = Main pulmonary artery.
against which sac contact can maintain its position.62 The closure rates.150 A modification of the duct-occlud device is the
device is not technically suitable for PDA more than 6 mm in reinforced device that has a cone-shaped appearance instead
size and for infants less than 3 kg as the delivery sheath is 8 of hourglass and achieves denser coil looping in the PDA
F. Using strict criterias for its use, only one-third of the cases facilitating total occlusion. Nit-occlud device is a modification
were found suitable by Ebeid et al.149 The prospective larger of the reinforced device and has same clinical configuration
clincial trials have not been done. but is made of nitinol-titanium alloy, which has higher shape
memory than steel coils and is suited for Type A conical
Duct-occlud and Nit-occlud Device PDAs (Figures 8A to C). The European registry and United
States Food and Drug Administration (US-FDA) trial reported
The duct-occlud device was developed to have a proper match successful implants in 90 percent and 77 percent respectively. In
318 with the size and shape of the PDA with a high stability during the former trial, there was a report of rupture of PDA that needed
and after closure, as well as for achieving higher complete surgical intervention and pulmonary artery embolization in 3.4
21
Amplatzer Devices
There are various types of Amplatzer duct occluders and
devices to close the PDA (Figures 9 A to D).
1. Amplatzer duct occluder (ADO): It was designed to a B
overcome the drawbacks of the other devices used in the
recent past. This occluder has gained popularity owing to its
user friendly delivery system, needing low fluoroscopic time,
easy repositioning and adaptation to all anatomical variations
of PDA (Figure 9A). It is the only FDA approved device and
is available in various sizes from 5/4 to 16/14 mm, can be
delivered through 5 to 8 F sheath; closes the ductus by stenting
the communication with its tubular part and by thrombosis.129 c D
Calibrated angiography is done to select the specific occluder figures 9a to D: A. Amplatzer duct occluder with the retention disc
for a given PDA. In general, a device is chosen so that the on aortic end; B. Amplatzer muscular ventricular septal occluder with
retention disc on both the sides; C. Amplatzer duct occluder II with
diameter of the pulmonary arterial end of the device is 2 to 3
two retention discs of 3 mm on either side with central cylinder with no
mm larger than the narrowest diameter of the ductus (usually polyester material; D. Amplatzer duct occluder II AS is additional size
the pulmonary end of the ductus) (Figures 10A and B). with a bigger central cylinder
Although for the selection of the long delivery sheath there
are recommendations by the manufacturer, usually one size
higher is preferred by the operators. There are multiple studies to device implantation. The most concerning morbidity was
suggesting high level of safety and efficacy of ADO.129,151 Pass aortic obstruction in 1 and LPA stenosis in 2 (gradient > 20
et al in their multicenter USA trial performed to obtain FDA mm Hg) at 1 year. Device embolization occurred in one case
approval, included 439 patients with exclusion criteria of those requiring surgery, as retrieval is not always possible. Amongst
less than 5 kg, PVR more than 8 Wood units, inferior vena the devices currently available, ADO has the highest efficacy
cava thrombosis and sepsis.129 The procedure was successful and safety in closing PDA more than 5 mm.130
in 435 (99%) with PDA size of 0.9 to 11.2 mm. The efficacy Occasionally, large PDA may be encountered, which are
rate (echocardiographic complete occlusion of PDA) was not amenable to closure even with the largest available ADO.
99.7 percent at one year. Additionally, virtually every shape Such ductus have been closed with Amplatzer ventricular
of the ductus was closed using the ADO. The complication septal occluder and no pulmonary or aortic obstruction was
rate was 2.3 percent with a single death that was unrelated observed on follow-up.130,152 Angiographic ventricular 319
http://vip.persianss.ir
4
Shunt DefectS
a B
figures 10a and B: Descending aortic angiogram in left lateral view shows a large patent ductus arteriosus (PDA)
opacifying main pulmonary artery (MPA); B. 10 x 8 Amplatzer duct occluder (device) in situ. Check angiogram shows no residual shunt.
assessment in adults with large PDA may be potentially of the occluding device. Since PDA is a remnant of the sixth
imprecise due to the overlap between large aorta and aortic arch, it results in an acute angle with the descending
pulmonary artery. A compliant balloon may be used to assess aorta of 31.6 to 34.4 degree. For this, ADO with a 32 degree
the minimum diameter, configuration and distensibility of the angled retention disc was specially designed and its initial
PDA or intravascular ultrasound imaging can be done.153 human experience confirms it to be safe and efficacious for
Kinking of the delivery sheath commonly occurs and it infants having small PDA ampulla/window type ductus
mandates selection of kink resistant sheath with optimal shape (Figures 11A and B).19,157
and length.154 Fischer et al evaluated the role of ADO in eleven 3. Amplatzer plug device: Amplatzer vascular plug without
infants with PDA measuring angiographically 1.5 to 5 mm.155 retention disc can be deployed in very small children to avoid
The procedure was successful in 82 percent and residual obstruction in aorta and pulmonary artery. Thanopoulous
flow was seen in one patient at 24 hours, which subsequently et al attempted it in nine children, aged 0.5 to 3 years, PDA size
disappeared at 45 days follow-up. But technical problems 1.5 to 10.5 mm.158 Success rate was 100 percent but one patient
in advancing the device through sheath at right ventricular with large PDA had residual shunt with hemolysis and required
outflow tract (RVOT) occurred in 75 percent. The closure of two coils for complete occlusion. This experience is however
large PDA in very small infants was considered challenging in limited and larger clinical trials are needed.
the past and not recommended by the device manufacturers. 4. Amplatzer duct occluder II (ADO II): Recently,
But a recent study shows device closure of large PDA, in ADO II is a specially designed for long ducts in infants
infants weighing ≤ 6 kgs was successful in 60/61 infants has become available for transcatheter closure of PDA.
(98.4%). The age, ranged from 9 days–12 months (mean 8.9 This newer generation device, ADO II, is a self expanding
months), weight ranged from 2.2 to 6 kg (mean 5.3 kg), and device with 2 retention discs (at both aortic and pulmonary
PDA measured 3.2 to 8.7 mm (mean 4.8 mm). The largest ends) that articulate with a central plug, which is sized to
device used was 12 × 10 mm. Mild aortic obstruction occurred the diameter of the midpoint of the PDA and is composed
in 2 cases (3.3%), as the device got displaced towards the small of fine Nitinol wire mesh with no polyester fabric (Figure
aorta after release. The device embolized in 2 cases (3.3%). 9 C). The advantage of the ADO II is that it has a very low
In one it was retrieved by a novel method like fastening the profile and can be easily delivered through a 4 or 5 F sheath
screw in the aorta and was subsequently closed with a 4 × 6 in infants. As it has a retention skirt on either side, it can
Amplatzer duct occluder II. Left pulmonary artery obstruction be delivered either from the pulmonary or the aortic end,
occurred in one case (1.6%). Four cases (6.6%) had minor which is especially useful in infants with severe pulmonary
vascular complications.156 hypertension. The ADO II with its thin delivery cable and
2. Angled Amplatzer duct occluder: Regular ADO however more flexible kink-resistant sheath makes the crossing of
was not found very suitable for infants and small children due the RVOT very easy in infants. The ADO II is delivered
to the possibility of encroachment into LPA or aorta causing through a TorqVue low profile catheter (St. Jude Medical,
320 significant hemodynamic obstruction as a result of protrusion Plymouth, MN), which comes in 4 and 5 French sizes.
21
http://vip.persianss.ir
4 Special Situations as an indication for ductus closure, follow-up results of
Francis et al have shown that decline in PA pressure to
half of the systemic pressure is predictive of favorable
Pulmonary Artery Hypertension
Shunt DefectS
a B c
figures 13a to c: A. Aortic angiogram in a 14 years old girl in right anterior oblique view shows large tubular duct measuring 13 mm and ampulla
21 mm; B. Balloon cocclusion of ductus was done and simultaneously pressure was monitored by another catheter through additional venous
access (arrow). Pulmonary artery pressure -115/80 mean 92 mm Hg, Aortic pressure-120/80 mean 93 mm of Hg; C. Aortic angiogram in left
lateral view illustrates Lifetech 18 x 16 duct occluder in situ, with no residual shunt. Post procedure, the pulmonary artery pressure dropped to
86/39 mean 55 and aortic pressure increased to 130/85 mean 100 mm of Hg
a B
figures 14a and B: a. Aortic angio in left lateral view in a 10 years old girl showed 20 mm window type B patent ductus arteriosus (PDA); B. 20
mm muscular ventricular septal defect (MVSD) device in situ. The pulmonary artery pressure decreased from 120/80 mean 93 to 78/57 mean 60
322 mm Hg. The oxygen saturation (SaO2) preprocedure in upper limb—92%, lower limb—84% and this improved to 98% after device closure. After
3 months on follow-up pulmonary artery pressure had come down to 50 mm Hg and after 1 year the pulmonary arterial systolic pressure was 30
mm Hg and SaO2-98%. Ao = Aorta; MPA = Main pulmonary artery.
Retrieval of embolized device could be tricky and Adult Patients 21
challenging. At times the embolised device caught by With advancing age, the morphologic characteristics of
the regular snare, if not coaxial with the sheath, wrinkles the ductus changes, altering the success of any procedure
a B
figures 15a and B: A. The device caught by regular 10 mm goose neck snare is not coaxial with the sheath (arrow)
and sheath is wrinkled (arrow); B. The basket type of snare used to catch the device
323
http://vip.persianss.ir
4
Shunt DefectS
a B
c D
figures 17a to D: Patent ductus arteriosus (PDA) closure in a one year old with 4 mm ductus and severe
coarctation of aorta. A. Aortogram showing a conical PDA with coarctation of aorta; B. Deployment of 8 x
6 Amplatzer duct occluder (Device); C. Balloon dilatation of the coarcted segment; D. Aortogram showing
complete occlusion of PDA and opened up coarcted segment (white arrow)
be stented.165 Alternatively, a covered stent may be deployed (pleural effusion, chylothorax, bleeding, pneumothorax, etc)
both to close the PDA and to repair the coarctation.166 PDA can result in prolonged mechanical ventilation and intensive
can be closed by using ADO with concomitant dilatation of care stay.131 Encouraged by the successful coil closure of
the coarcted segment (Figures 17A to D). large ducts especially with the availability of 0.052″ coils,138
the procedure has been attempted for five small sick ventilated
Sick Ventilated Small Infants infants, weighing 0.960 to 4.0 kg.170 Bioptome-assisted coil
delivery was done and PDA closure was achieved in all. There
Large PDA in full-term/premature babies is known to cause were two instances of embolization of coils with successful
CHF early in life.167 Superadded respiratory infections are not retrieval and redeployment. All infants could be weaned
uncommon and can result in respiratory insufficiency requiring off mechanical ventilation over the next 24 to 72 hours and
ventilatory support. When medical therapy with indomethacin remained asymptomatic at 3 months follow-up. But only ducts
(for preterms), fluid restriction and diuretics fails, closure of the with adequate ampulla are suitable and the procedure needs
PDA becomes a necessity. Surgical ligation by open thoracotomy certain degree of expertise.
is the standard treatment.144 This can be done even on site in the
neonatal intensive care units, avoiding the risk of transferring Marfan Syndrome
unstable neonates.168 Moreover, video-assisted thoracic surgery
has been proved to be effective and minimally traumatic in Younger patients with connective tissue abnormalities may also
324 premature infants with very low birth weight.169 This facility be at risk for development, progression and rupture of ductal
is not however uniformly available. Surgery related morbidities or aortic aneurysms after device closure. Marasini et al171
with coil occlusion.131,138,139,173 Residual shunts129 are 21
classified as:
a. ‘Smoke’ like with no jet.
http://vip.persianss.ir
4 assisted closure of PDA has been attempted and found
comparable with closure by means of videoscopic technique.
However, it appears more complicated, demanding and time
Shunt DefectS
Contraindications
and lower borders of the ductus. Hemostasis is checked, pleura is
1. Severely elevated PVR (> 8 Wood units). covered and the chest is closed. In small children an extra pleural
2. Failure of PVR to fall (< 8 Wood units) with isoproterenol approach can also be attempted.
during cath study at 0.14 mg/kg/min. Closure from the midline sternotomy approach is done in
3. Qp:Qs of 1.5 to 1.8 at rest that becomes < 1 during exercise. cases where ligation is being done along with concomitant
4. Ductal dependent lesions. repair of the cardiac lesions, difficult ductus arteriosus and
residual ductus. It is also required to be done after device
Procedure embolization.The procedure is done by applying traction to
the MPA and the PDA appears like a ‘continuity’ of the MPA.
The PDA has to be controlled in all patients undergoing The right and left pulmonary arteries are noted and ligation
surgery under CPB as the presence of an open PDA during of the ductus is done before CPB or at the initiation of CPB.
CPB can cause flooding of the lungs and distention of the LV In case of a complicated ductus, the ductus is temporarily
in the arrested heart on CPB. The PDA is ligated or divided. interrupted by invaginating the MPA with a finger to occlude
Cardiopulmonary bypass is required in special circumstances the ductal orifice, while CPB is established. A balloon
like a calcified ductus, ductal aneurysm or a friable ductus with catheter may be placed to occlude the PDA after opening the
endarteritis. The usual approach is through the fourth intercostal MPA during a period of temporary low flow. After cooling
space through a posterolateral thoracotomy. A video-assisted the patient to the required temperature, head low position
thoracoscopic approach can also be used. Some surgeons ligate is given and under low flows, the orifice of the PDA is
the ductus through a minithoracotomy incision. The lung is gently closed with a patch or directly depending on the size of the
retracted and the ductus and the posterior pleura is incised. The ductus.
superior intercostal vein is divided and stay sutures are placed. It
is ensured that there is adequate blood present in the operating Complications
room, suction apparatus is functioning and the ductus clamps
are checked. Under hypotensive anesthesia, sharp and blunt Bleeding is a major complication and can occur during
dissection of the ductus arteriosus is done and the aorta above looping the ductus and also during division of the ductus.
and below the ductus are defined. The pericardial lappet needs Recanalization can occur both after ligation and even rarely
to be dissected and lifted off to allow definition of the ductus after division. Device closure of a residual ductus can be
(Figure 19). The ligatures are passed around the ductus and under done. Chylothorax due to division of lymphatics or thoracic
controlled hypotension the ductus arteriosus is ligated. In case duct, hematomas and recurrent laryngeal nerve injury can also
of a hypertensive ductus, a trial clamping may be done initially occur after ductal ligation through a thoracotomy.
and if there is any bradycardia and hypotension after clamping In premature infants, the operative mortality is related more
the ductus, the clamps may be released. If division is planned, due to the associated comorbid conditions and associated medical
ductus clamps are placed and the ductus is divided and running problems and can be as high as 10 to 15 percent. Uncomplicated
326 sutures are placed over both ends and clamps are removed. In ductal ligation is associated with minimal mortality. The
neonates, a large hemoclip can be placed after defining the upper recanalization can occur in upto 0.5 percent of cases.
ConCLuSIon
16. Rao PS, Wilson AD, Sideris EB, et al. Transcatheter closure of 21
The ductus arteriosus is an important and essential normal patent ductus arteriosus with buttoned device: first successful
structure during fetal development and usually undergoes clinical application in a child. Am Heart J. 1991;121:1799-
http://vip.persianss.ir
4 35. Mitchell SC, Korones SB, Berendes HW. Congenital heart
disease in 56, 109 births. Incidence and natural history.
57. Kanamaru H, Karasawa K, Miyashita M, et al. Successful
multiple coils embolization for bilateral patent ductus arterio-
Circulation. 1971;43:323-32. sus with isolated subclavian artery. Pediatr Int. 2006;48:510-3.
Shunt DefectS
36. Lloyd TR, Beekman RH 3rd. Clinically silent patent ductus 58. Kirklin JW, Barratt-Boyes BG. Cardiac Surgery. 2nd edn. New
arteriosus. Am Heart J. 1994;127:1664-5. York: Churchill Livingstone; 1993. p. 841.
37. Benson LN, Cowan KN. The arterial duct: its persistence and its 59. Hoffman J. Patent Ductus Arteriosus. In: Hoffman J (Ed). The
patency. In: Anderson RH, Baker EJ, Macartney FJ, Rigby ML, Natural and Unnatural History of Congenital Heart Disease.
Shinebourne EA, Tynan M (Eds). Paediatric Cardiology. 2nd USA: John Wiley and Sons Ltd; 2009. pp. 79-92.
edition. London: Churchill Livingstone. 2002. pp. 1405-59. 60. Basave M, Rangel A, Albarran H, et al. Unusual giant patent
38. Brook MM, Heyman MA. Patent ductus arteriosus. In: ductus arteriosus associated with ventricular septal defect and
Emmanouilides GC, Riemenschneider TA, Allen HD, et al. discrete aortic coarctation. A case report. Arch Cardiol Mex.
(Eds): Heart Disease in Infants, Children and Adolescents. 2001;71:146-50.
Baltimore. Williams and Wilkins; 1995. pp. 746-63. 61. PS Rao. Management of Patent ductus Arteriosus with
39. Evans N. Diagnosis of patent ductus arteriosus in the preterm emphasis on Transcatheter Therapy. 4th International Congress
newborn. Arch Dis Child. 1993;68:58-61. of Cardiology on the internet 2005.
40. Campbell M. Natural history of persistent ductus arteriosus. Br 62. Krichenko A, Benson L, Burrows P, et al. Angiographic
Heart J. 1968;30:4-13. classification of the isolated persistently patent ductus arteriosus
41. Clyman RI. Ductus arteriosus: Current theories of prenatal and and implications for percutaneous catheter occlusion. Am J
postnatal regulation. Semin Perinatol. 1987;11:64-71. Cardiol. 1989;63:877-80.
42. Eronen M, Kari A, Pesonen E, et al. The effect of antenatal 63. Abrams SE, Walsh KP. Arterial duct morphology with reference
dexamethasone administration on fetal and neonatal ductus to angioplasty and stenting. Int J Cardiol. 1993;40:27-33.
arteriosus: A randomized double blind study. Am J Dis Child. 64. Alwi M. Stenting the ductus arteriosus: Case selection,
1993;147:187-92. technique and possible complications. Ann Pediatr Cardiol.
43. Nora JJ. Multifactorial inheritance hypothesis for the etiology 2008;1:38-45.
of congenital heart disease: the genetic-environmental 65. Gittenberger-de Groot AC, Van Ertbruggen I, Moulaert AJ,
interaction. Circulation. 1968;38:604-17. et al. The ductus arteriosus in the preterm infant: histologic and
44. Nora JJ, Nora AH. Update on counselling the family with clinical observations. J Pediatr. 1980;96:88-93.
first degree relative with a congenital heart defect. Am J Med 66. Rudolph AM, Drorbraugh JE, Auld PA, et al. Studies on
Genet. 1988;29:137-42. the circulation in the neonatal period. The circulation in the
45. Zetterquist P. A Clinical and Genetic Study of Congenital Heart respiratory distress syndrome. Pediatrics. 1961;27:551-66.
Defects. Sweden: University of Uppsala; 1972. pp. 1-80. 67. Fay FS, Cooke PH. Guinea pig ductus arteriosus. II. Irreversible
46. Wilkins J. Risks of offspring of patients with patent ductus closure after birth. Am J Physiol. 1972;222:841-9.
arteriosus. J Med Genet. 1969;6:1-3. 68. Gittenberger-de Groot AC. Persistent ductus arteriosus: most
47. Polani PE, Campbell M. Factors in the causation of persistent probably a primary congenital malformation. Br Heart J. 1977;
ductus arteriosus. Ann Hum Genet. 1960;24:343-57. 39:610-8.
48. Lamy M, de Grouchy J, Schweisguth O. Genetic and non- 69. Gittenberger-de-Groot AC, Strengers JL, Mentink M.
genetic factors in the etiology of congenital heart disease: a Histologic studies on normal and persistent ductus arteriosus
study of 1188 cases. Am J Hum Genet. 1957;9:17-41. in the dog. J Am Coll Cardiol. 1985;6:394-404.
49. Forsey JT, Elmasry OA, Martin RP. Patent arterial duct. 70. Langer C. Zuranatomie der fotalenkreislaufsorgane. Z Ges
Orphanet J Rare Dis. 2009;4:17. Wien Arzte. 1857;13:328-38.
50. Nora JJ, Nora AH. The evolution of specific genetic and 71. Olley PM, Coceani F. Lipid mediators in the control of the
environmental counselling in congenital heart disease. ductus arteriosus. Am Rev Respir Dis. 1987;136:218.
Circulation. 1978;57:205-13. 72. Nguyen M, Camenisch T, Snouwaert JN, et al. The prostaglandin
51. Anoop P, Sasidharan CK. Patent ductus arteriosus in fetal receptor EP4 triggers remodelling of the cardiovascular system
valproate syndrome. Indian J Pediatr. 2003;70:681-2. at birth. Nature. 1997;390:78.
52. Gibson S, Lewis K. Congenital heart disease following maternal 73. Segi E, Sugimoto Y, Yamasaki A, et al. Patent ductus arteriosus
rubella during pregnancy. Am J Dis Child. 1952;83:117-9. and neonatal death in prostaglandin receptor EP4-deficient
53. Swan C, Tostevin AL, Black GHB. Final observations on mice. Biochem Biophys Res Commun. 1998;246:7.
congenital defects in infants following infectious disease 74. Smith GC. The pharmacology of the ductus arteriosus.
during pregnancy with special reference to rubella. Med J Aust. Pharmacol Rev. 1998;50:35.
1946;2:889-908. 75. Heymann MA, Rudolph AM. Control of the ductus arteriosus.
54. Knight L, Edwards JE. Right aortic arch. Types and associated Physiol Rev. 1975;55:62.
cardiac anomalies. Circulation. 1974;50:1047-51. 76. Kozik D, Ivy D, Ibrahim J, et al. Patent Ductus Arteriosus.
55. Carr MR, Neish SR, Leonard GT. Successful transcatheter In: Munoz R, Morrell V, da Cruz E, Vetterly C (Eds). Critical
coil occlusion of a right-sided patent ductus arteriosus Care of Children with Heart Disease: Basic Medical and
with aberrant left subclavian artery. Tex Heart Inst J. Surgical Concepts. Springer-Verlag London Limited; 2010.
2006;33:365-7. pp. 145-57.
56. Vida VL, Veras O, Leon-Wyss J, et al. The right-sided window 77. Rudolph AM. Congenital Diseases of the Heart: Clinical-
ductus: a rare anatomical entity. Ann Thorac Surg. 2006;81: Physiologic Considerations in Diagnosis and Management.
328
1126-7. Chicago: Year Book Medical. 1974.
78. Barnes N, Archer N. Understanding congenital heart disease.
Current Paediatrics. 2005;15:421-8.
98. Serwer GA, Armstrong BE, Anderson PA. Noninvasive
detection of retrograde descending aortic flow in infants using
21
79. Vijaya MJ, Sepehr S. Acyanotic Congenital heart defects. In continuous wave Doppler ultrasonography. Implications for
http://vip.persianss.ir
4 119. Berger M, Ferguson C, Hendry J. Paralysis of the left
diaphragm, left vocal cord, and aneurysm of the ductus
in the Young; Council on Clinical Cardiology; Council on
Cardiovascular Radiology and Intervention; American Heart
arteriosus in a 7-day-old infant. J Paediatr. 1960;56:800-02. Association. Circulation. 2011; 123: 2607-52.
Shunt DefectS
120. Roughneen PT, Parikh P, Stark J. Bronchial obstruction 138. Kumar RK, Krishnan MN, Venugopal K, et al. Bioptome-
secondary to aneurysm of a persistent ductus arteriosus. Eur J assisted simultaneous delivery of multiple coils for occlusion
Cardiothorac Surg. 1996;10:146-7. of the large patent ductus arteriosus. Cathet Cardiovasc Interv.
121. Dyamenahalli U, Smallhorn JF, Geva T, et al. Isolated ductus 2001;54:95-100.
arteriosus aneurysm in the fetus and infant: a multi-institutional 139. Kumar RK, Anil SR, Kannan BRJ, Philip A, Sivakumar K.
experience.J Am Coll Cardiol. 2000;36:262-9. Bioptome-assisted coil occlusion of moderate-large patent
122. Roques F, Hennequin JL, Sanchez B, et al. Aortic stent-graft arterial ducts in infants and small children. Catheter Cardiovasc
for patent ductus arteriosus in adults: the aortic exclusion Interv. 2004;62:266-71.
technique. Ann Thorac Surg. 2001;71:1708-09. 140. Wang JK, Liau CS, Huang JJ, et al. Transcatheter closure of
123. Mosca F, Bray M, Lattanzio M, et al. Comparative evaluation patent ductus arteriosus using Gianturco coils in adolescents
of the effects of indomethacin and ibuprofen on cerebral per- and adults. Cathet Cardiovasc Interv. 2002;55:513-8.
fusion and oxygenation in preterm infants with patent ductus 141. Moore JW, George L, Kirkpatrick SE, et al. Percutaneous
arteriosus. J Pediatr. 1997;131:549-54. closure of small patent ductus arteriosus using occluding
124. Pezzati M, Vangi V, Biagiotti R, et al. Effects of indomethacin spring coils. J Am Coll Cardiol. 1994;23:759-65.
and ibuprofen on mesenteric and renal blood flow in preterm 142. Galal MO, Bulbul Z, Kakadekar A, et al. Comparison
infants with patent ductus arteriosus. J Pediatr. 1999;135:733-78. between the safety profile and clinical results of the Cook
125. Chotigeat U, Jirapapa K, Layangkool T. A comparison of detachable and Gianturco coils for transcatheter closure of
oral ibuprofen and intravenous indomethacin for closure of patent ductus arteriosus in 272 patients. J Interven Cardiol.
patent duct arteriosus in preterm infants. J Med Assoc Thai. 2001;14:169-71.
2003;86:S563-9. 143. Hijazi ZM, Geggel RL. Results of anterograde transcatheter
126. Hammerman C, Aramburo MJ. Prolonged indomethacin closure of patent ductus arteriosus using single or multiple
therapy for the prevention of recurrences of patent ductus Gianturco coils. Am J Cardiol. 1994;74:925-9.
arteriosus. J Pediatr. 1990;117:771-6. 144. Mavroudis C, Backer CL, Gevitz M. Forty-six years of
127. Rennie JM, Cooke RW. Prolonged low dose indomethacin for patent ductus arteriosus division at Children’s memorial
persistent ductus arteriosus of prematurity. Arch Dis Child. Hospital of Chicago: Standards for comparison. Ann Surg.
1991;66:55-8. 1994;1220:402-9.
128. Knight DB. The treatment of patent ductus arteriosus in 145. Rao PS, Kim SH, Choi JY, et al. Follow-up results of
preterm infants. A review and overview of randomized trials. transvenous occlusion of patent ductus arteriosus with the
Semin Neonatol. 2001;6:63-73. buttoned device. J Am Coll Cardiol. 1999;33:820-6.
129. Pass RH, Hijazi ZM, Hsu DT, et al. Multicenter USA Amplatzer 146. Sideris EB, Rao PS, Zamora R. The Sideris buttoned devices
patent ductus arteriosus occlusion device trial. J Am Coll for transcatheter closure of patent ductus arteriosus. J Inter
Cardiol. 2004;44:513-9. Cardiol. 2002;14:239-46.
130. Arora R. Transcatheter devices for large patent ductus arterio- 147. Wilson NJ, Occleshaw CJ, O’Donnell CP, et al. Subclinical
sus. Cardiology Today. 2004;8:121-3. aortic perforation with infant double-button patent ductus
131. LeBlanc JG, Russell JL, Sett SS, Potts JE, Human DG, Culham arteriosus occluder. Catheter Cardiovasc Interv. 1999;48: 296-8.
JA. The evolution of ductus arteriosus treatment. Int Surg 148. Grifka RG, Miller MW, Frischmeyer KJ, et al. Transcatheter
2000;85:1-5. occlusion of patent ductus arteriosus in a Newfoundland puppy
132. Leon-Wyss J, Vida VL, Veras O, et al. Modified extrapleural using the Gianturco-Grifka vascular occlusion device. J Vet
ligation of patent ductus arteriosus: a convenient surgical Intern Med. 1996;10:42-44.
approach in a developing country. Ann Thorac Surg. 149. Ebeid MR, Gaymes CH, Smith JC, et al. Gianturco-Grifka
2005;79:632-5. vascular occlusion device for closure of patent ductus
133. Rao PS. Transcatheter occlusion of patent ductus arteriosus: arteriosus. Am J Cardiol. 2001;87;657-60.
which method to use and which ductus to close. Am Heart J. 150. Moore JH, Schneider DJ, Dimeglio D. The duct-occlud device:
1996;132:905-09. design, clinical results and future directions. J Interv Cardiol.
134. Schrader R, Kadel C. Persistent ductus arteriosus–is closure 2001;14:231-8.
indicated also in asymptomatic adults with small ductus and 151. Faella HJ, Hijazi ZM. Closure of the patent ductus arteriosus
minor shunt? Z Kardiol. 1993;82:563-7. with the amplatzer PDA device: immediate results of the
135. Balzer DT, Spray TL, McMullin D, et al. Endartiritis associated international clinical trial. Catheter Cardiovasc Interv
with a clinically silent patent ductus arteriosus. Am Heart J. 2000;51:50-4.
1993;125:1192-3. 152. Pedra CA, Sanches SA, Fontes VF. Percutaneous occlusion of
136. Bennhagen RG, Benson LN. Silent and audible persistent the patent ductus arteriosus with the amplatzer device for atrial
ductus arteriosus. An angiographic study. Pediatr Cardiol. septal defects. J Invasive Cardiol. 2003;15:413-7.
2003;24:27-30 153. Hijazi ZM, Ahmad WH, Geggel RL, et al. Intravascular
137. Feltes TF, Bacha E, Beekman RH 3rd, et al. Indications for ultrasound during transcatheter coil closure of patent ductus
cardiac catheterization and intervention in pediatric cardiac arteriosus: comparison with angiography. J Invasive Cardiol.
disease: a scientific statement from the American Heart 1998;10:251-4.
330
Association. American Heart Association Congenital Cardiac 154. Duke C, Chan KC. Aortic obstruction caused by device
Defects Committee of the Council on Cardiovascular Disease occlusion of patent arterial duct. Heart. 1999;82:109-11.
155. Fischer G, Stieh J, Uebing A, et al. Transcatheter closure of arteriosus using a covered stent. Cathet Cardiovasc Interv.
2003;59:387-90.
21
persistent ductus arteriosus in infants using the Amplatzer duct
occluder. Heart. 2001;86:444-7. 167. Alter BP, Czapek EE, Rowe RD. Sweating in congenital heart
331
http://vip.persianss.ir
C hapter
22 Aortopulmonary Window
INTRODUCTION CLASSIFICATION
Aortopulmonary window (APW) or aortopulmonary septal Aortopulmonary window, a defect in the aortopulmonary
defect is a rare congenital heart disease occurring in 0.2 to septum, is classified into various types by different authors.
0.6 percent of all patients with congenital heart disease.1 Mori et al classified the APW into three types3:
APW was first described by John Elliotson in 1830.1 APW Type I or proximal defect is the most common (70–96% of
represents a communication between ascending aorta and cases) and occurs in the proximal part of the aortopulmonary
pulmonary trunk. It is characterized by the presence of well- septum. They are located just above the semilunar valves.
defined and separate aortic and pulmonary valves, unlike in Type II or distal defect (14–25%) occurs in the distal part of
truncus arteriosus, where only an isolated truncal valve is aortopulmonary septum adjacent to the right pulmonary artery
noted.2 Half of the patients with APW are associated with (RPA). They involve the pulmonary bifurcation at the level of
other cardiac defects. The most common associated defect is the RPA. This form may be associated with type A IAA.8
the type A interrupted aortic arch (IAA). The other associated Type III or total defect (5%) is a large confluent defect
cardiac defects includes aortic origin of right pulmonary where there is total absence of the aortopulmonary septum.
artery, anomalous origin of right coronary or left coronary Later Ho et al9 modified the above classification of APW
artery from pulmonary artery, tetralogy of Fallot, patent ductus into four types according to its morphologic features:
arteriosus (PDA) and right aortic arch. It is rarely associated 1. Proximal defect is between the ascending aorta and the
with ventricular septal defect (VSD).3-5 main pulmonary artery, having little inferior rim separating
the APW from the semilunar valves.
Synonyms 2. Distal defect is between origin of the RPA and ascending
aorta having a well-formed inferior rim, but little superior
The synonyms like aortopulmonary septal defect, aortopul- rim. This defect is associated with aortic origin of the RPA.
monary fenestration or aortopulmonary fistula are not com- 3. Confluent defect, is a combination of the first and second
monly used. types with little superior and inferior rims.
4. Intermediate type is characterized by adequate superior and
EMBRyOLOGY inferior rims. It is the intermediate type of defect, which is
best suited for device closure (Figure 1).
The aortopulmonary septum is formed during early em- Kutsche and Van Mierop described three types of aorto-
bryogenesis by the opposing truncal cushions which fuse pulmonary defect:
to divide the truncus arteriosus into aortic and pulmonary 1. A defect with a circular border located between the
channels.6 Maldevelopment of this aortopulmonary sep- semilunar valves and pulmonary bifurcation.
tum leads to the development of APW. Unlike truncus 2. A similarly located fenestration in which the border
arterious, APW is not associated with DiGeorge syndrome.7 represents a helix.
22
Aortopulmonary Window
Figure 1: Diagrammatic representation of types of aortopulmonary window (APW). (Reprinted from Barnes ME, Mitchell ME, Tweddell JS.
Aortopulmonary window. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2011;14:67-74, with permission from Elsevier)
3. A large defect with no posterior or distal border. According resistance, and the presence of associated defects. Clinical
to the author the first type may reflect non-fusion of features of APW are those of a large left-right shunt. Clinically
aortopulmonary septum and truncal septum. The second APW is indistinguishable from PDA. Signs of congestive heart
type suggests malalignment of the aortopulmonary septum failure (tachypnea, diaphoresis, failure to thrive and recurrent
and truncal septum, while the third type result from total respiratory infections) develops during first week of life. If
absence of embryonic aortopulmonary septum.1,6 associated with aortic arch anomalies, the patient can present
in the neonatal period with metabolic acidosis and cardiogenic
Natural History and Hemodynamics shock following the closure of PDA.
Clinical examination reveals tachypnea and intercostal
There is neither the tendency for APWs to close spontaneously retraction, a bounding arterial pulse and wide pulse
nor does the defect size decrease with time and growth pressure similar to nonrestrictive PDA with low pulmonary
of the patient. The defect is variable in size, but all defects vascular resistance. On auscultation second heart sound
result in a large and generally continuous left-to-right shunt, is accentuated and narrowly split indicating pulmonary
when the pulmonary vascular resistance falls, similar to hypertension.3,12 Large nonrestrictive APW generates a
other interarterial communications such as PDA or truncus loud systolic ejection murmur at the third left intercostal
arteriosus.7 After the immediate perinatal period there is space along with eddy sounds. Apical mid-diastolic murmur
enlargement of left atrium and left ventricle. The pulmonary is heard which represents increased flow across the mitral
arteries are dilated due to the increased pulmonary blood flow. valve.
The ascending aorta can be small in patients with APW with Moderately, restrictive APW generates a continuous
proximal defects or with associated arch anomalies.10 Without murmur in the upper left sternal border. Large APW associated
corrective surgery, irreversible obstructive changes in the with severe pulmonary arterial hypertension (PAH) and
pulmonary vascular bed develop early, followed by death in reversed shunt presents with Graham Steell murmur due to
the second decade, although patients surviving into the 4th the marked dilatation of hypertensive pulmonary trunk.
decade have been reported.5,11 There is an interesting report
of a patient with Eisenmenger syndrome secondary to a large Differential Diagnosis
unrepaired APW who gave birth to three children in her 30s,
survived into her 50s with relatively preserved quality of life, The signs and symptoms mimics large PDA and truncus
and died at age 60 years.12 The defect is small in about 10 arteriosus (Type I). In APW associated VSD and right-sided
percent of patients and they usually present late in childhood aortic arch are extremely rare.
like any other moderate sized left-to-right shunt.
ELECTROCARDIOGRAPHY
CLINICAL FEATURES
There is no characteristic electrocardiography (ECG) finding
The clinical presentation is determined by the size of the defect, in patients with APW. Large APW is characterized by
the relationship between systemic and pulmonary vascular biventricular hypertrophy (Figure 2). 333
http://vip.persianss.ir
4
Shunt Defects
Figure 2: ECG in APW shows volume overload of LV with RVH due to PAH. ECG = Electrocardiography; LV = Left ventricle;
APW = Aortopulmonary window; RVH = Right ventricular hypertrophy; PAH = Pulmonary arterial hypertension
Cardiac Catheterization
In the current era of good resolution echocardiography,
cardiac catheterization is rarely indicated for the diagnosis of
APW. The right ventricular and pulmonary artery pressures
are systemic. In the presence of large defects, aortic diastolic
pressure is low with wide pulse pressure. The catheter can be
manipulated into ascending aorta from the pulmonary artery.
An ascending aortogram in shallow right arterior oblique
projection reveals the defect with opacification of the main
Figure 3: X-ray chest posteroanterior (PA) view shows cardiomegaly pulmonary artery (Figures 5A and B) and demonstrates arch
with biventricular hypertrophy with prominent MPA with plethora
anomalies.3 Main pulmonary artery angiogram shows filling
of the ascending aorta and when present the anomalous orgin
of the coronary artery from the pulmonary artery can be
Radiological Features
demonstrated.
The chest X-ray shows cardiomegaly with left ventricular
contour, LA enlargement and plethoric lung fields are seen TREATMENT
in patients with large APW (Figure 3). The aortic knuckle
is not prominent in contrast to PDA. Peripheral pruning of World literature on transcatheter closure of APWs is limited
pulmonary vessels with prominent main pulmonary artery to closure of restrictive defects, that too in adults or older
indicates severe pulmonary artery hypertension. children. Different operators have used different types of
devices for percutaneous closure of APWs including umbrella
Echocardiography device, Amplatzer septal occluder and duct occluders.
Intermediate type defect, which has adequate superior and
Two-dimensional echocardiography reveals dilatation inferior rims is best suited for device closure. There are few
of the left atrium and left ventricle. The right ventricle case reports of device closure of non-restrictive APW in
334 may be hypertrophied with significant dilatation of infants.14-16 Depending on the PA pressure either Amplatzer
pulmonary arteries. APW is usually seen as a dropout in the duct occluder or Amplatzer septal muscular occluder is
22
Aortopulmonary Window
A B
Figures 4A and B: A. Parasternal short axis view shows drop out in the aortopulmonary area; B. Color Doppler shows left to right shunt.
AO = Aorta; APW = Aortopulmonary window; LPA = Left pulmonary artery; MPA = Main pulmonary artery; RA = Right atrium; RPA = Right
pulmonary artery; RV = Right ventricle.
A B
Figures 5A and B: Ascending aortogram in right anterior oblique shows opacification of dilated pulmonary artery (PA) through aortopulmonary
window (APW) type III large confluent defect involving the entire aortopulmonary septum; B. Aortic root angiogram in anterioposterior view shows
opacification of PA through APW type II (arrow).
used. If the APW is not delineated clearly with angiography, without extracorporeal circulation, through a transaortic or
then balloon sizing can be done. The standard arteriovenous transpulmonary approach, and with or without the use of a
loop is made and then selected device is introduced from patch. Transaortic approach allows close inspection of the
the venous end. The successful closure can be checked with coronary ostia, correction of arch anomalies and coronary
angiogram and also transthoracic echocardiogram (Figures anomalies.8 Recent revisions have used a pulmonary artery
6A to C). flap to close the defect and this technique avoids the use of
prosthetic material.
Surgery
Conclusion
Gross first successfully ligated an APW in 1948.17 This
technique was associated with distortion of the semilunar The survival of an infant with large APW, presenting with
valves and distortion of the left coronary artery. Several surgical congestive heart failure is poor. Approximately 20 to 30
techniques and modifications have been described, with or percent of large APW, patients die within 1 year. Early 335
http://vip.persianss.ir
4
Shunt Defects
A B C
Figures 6A to C: A. Aortic root angiogram shows Type IV aortopulmonary window (APW);; B. Shows 10 x
8 Amplatzer duct occluder (device) in situ; C. Transthoracic echocardiography in parasternal short axis view
with color Doppler shows device in situ with no residual shunt AO = Aorta; PA = Pulmonary artery
surgical closure with Dacron patch is the accepted modality 7. Marmon LM, Balsara RK, Chen R, et al. Congenital cardiac
of treatment. It has to be done before the child develop anomalies associated with the DiGeorge syndrome: A neonatal
severe PAH. Early detection of APW is very important as experience. Ann Thorac Surg. 1984;38:881-4.
they develops severe PAH very early in life. Transthoracic 8. Pillekamp F, Hannes T, Koch D, Brockmeier K, Sreeram N.
echocardiogram and and magnetic resonance imaging are Transcatheter closure of symptomatic aortopulmonary window
in an infant. Images Pediatr Cardiol. 2008;35:11-7.
useful for diagnosis. Transcatheter non-surgical device
9. Ho SY, Gerlis LM, Anderson C, Devine WA, Smith A. The
closure is useful in small restrictive APW.
morphology of aortopulmonary window with regard to their
classification and morphogenesis. Cardiol Young. 1994;4:146-55.
A smart mother makes often a better diagnosis than a poor 10. Moguillansky D, Munoz R, Morell VO. Aortopulmonary Window.
doctor. In Critical Care of Children with Heart Disease: Basic Medical
—August Bier and Surgical Concepts. Munoz R, Morrell V, da Cruz E, Vetterly
C (eds). Springer-Verlag London Limited; 2010: 191-197.
REFERENCES 11. LC Blieden and Moller JH. Aorticopulmonary septal defect.
An experience with 17 patients. Br Heart J. 1974;36:630-5.
1. Kutsche LM, Van Mierop LH. Anatomy and pathogenesis of 12. Su-Mei AK, Ju-Le T. Large unrepaired aortopulmonary
aorticopulmonary septal defect. Am J Cardiol. 1987;59:443-7. window—survival into the seventh decade. Echocardiography.
2. Mert M, Paker T, Akcevin A, et al. Diagnosis, management, 2007;24:71-3.
and results of treatment for aortopulmonary window. Cardiol 13. Balaji S, Burch M, Sullivan ID. Accuracy of cross-sectional
Young. 2004;14:506-11. echocardiography in diagnosis of aortopulmonary window.
3. Mori K, Ando M, Takao A, et al . Distal type Aortopulmonary Am J Cardiol. 1991;67:650-3.
window. Report of 4 cases. Br Heart J. 1978;40:681-9. 14. Atiq M, Rashid N, Kazmi KA, Qureshi SA. Closure of
4. Redington AN, Rigby ML, Ho SY, Gunthard J, Anderson RH. aortopulmonary window with Amplatzer duct occluder device.
Aortic atresia with aortopulmonary window and interruption of Pediatr Cardiol. 2003;24:298-9.
the aortic arch. Pediatr Cardiol. 1991;12:49-51. 15. Rohit M, Nandakumar S, Bahl A, Kubba S, Talwar KK.
5. Meisner H, Schmidt-Habelmann P, Sebenning F, Klinner Transcatheter closure of aortopulmonary window. Indian Heart
W. Surgical correction of aorto-pulmonary septal defects. A J. 2005;57:161-3.
review of the literature and report of eight cases. Dis Chest. 16. Sivakumar K, Francis E. Transcatheter closure of distal
1968;53:750-8. aortopulmonary window using Amplatzer Device. Congenit
6. Van Mierop LH S, Kutsche LM. Embrology of the Heart. In: Heart Dis. 2006;1:321-3.
Hurst JW, (Ed). The Heart. (6th edn) New York: McGraw-Hill, 17. Gross RE. Surgical closure of an aortic septal defect.
1986. Circulation. 1952;5:858-63.
336
C hapter
23 Aorticocameral Tunnels
http://vip.persianss.ir
4 involvement of the proximal coronary arteries and valve Schematic representation of the most common type of ALVT
leaflets. Thus, this is one of the few congenital malformations is shown in Figure 1.
which may simultaneously involve both the pulmonary and Anomalies of the aortic root are present in about half of
Shunt Defects
aortic valves.7,27 Nearly half of the aorticocameral tunnel these patients with tunnels.7,9,32,33 Aortic regurgitation is the
patients suffer from other cardiac defects particularly aortic most common association, probably due to the weakness of
valve and/or coronary artery anomalies.28,29 the aortic sinus wall, especially the unsupported right coronary
cusp with resultant aortic root ectasia.33,34 Aortic valve stenosis
Pathological Anatomy has been reported with bicuspid or unicuspid aortic valves.27,32
Severe aortic dysplasia or atresia can also occur.35,36
The aortoventricular tunnel is an abnormal channel that Valvular pulmonary stenosis37,38 occurs less frequently
connects the lumen of the ascending aorta to the cavity of (around 5%), while compression of the right ventricular out
either the left or right ventricle. The aortic opening of most flow tract by the tunnel may produce subpulmonary obstruc
tunnels lies above the right coronary sinus of Valsalva. The tion.27,39 Rarely, both semilunar valves are stenotic.7,27 An as
tunnel courses in the tissue plane between the free-standing sociated ventricular septal defect is rare,28,40 but there can be
muscular subpulmonary infundibulum and the aortic sinus an associated sinus of Valsalva aneurysm.33,41
and communicates with the left ventricle in the fibrous Aortoventricular tunnels have important relationships to
interleaflet triangle between the right and left coronary aortic the proximal portions of the coronary arteries.42 The ostium
leaflets or the right ventricle immediately above or below of a coronary artery may lie within an aortoventricular tunnel.
the subpulmonary infundibulum.30 Tunnels lying above Atresia of the left11,43 or right8,15,28,31,32,44,45 have both been
the left sinus of Valsalva or the intercoronary commissure observed with this anomaly.
have less uniform morphology and they virtually never
enter this fibrous triangle.9 The tunnel itself may be dilated Pathophysiology
aneurysmally through part or the entirety of its course.
The origin of the tunnel from the tubular aorta is above the The pathophysiological effect depends on the size of the
sinotubular junction, which differentiates it from the rupture tunnel and the amount of regurgitation. Interference with
of an aneurysm of sinus Valsalva. The ruptured sinus of coronary blood flow may be a contributing factor. Fetal
Valsalva aneurysm originates below the sinotubular junction hydrops or death has occurred when the tunnel has been large,
and remains completely within the heart. The differentiation antenatally.46 The large tunnels cause severe congestive heart
of the tunnel from the coronary-cameral fistula is less clear failure and most patients are symptomatic in infancy and most
as a coronary arterial orifice may arise above the sinotubular often under a month of age.32,33,40,44,47,48 Patients with smaller
junction and the coronary arteries have been found to arise tunnels are asymptomatic and present between 1 and 15 years
from within the aortoventricular tunnel.9 But the coronary- of age. But almost all have aortic valve regurgitation or signs
cameral fistula passes through the myocardium to enter the of left ventricular dilatation and hypertrophy. The oldest
cardiac chamber and does not involve the hingepoint of an patient presented at 63 years of age with multiple tunnels.3
aortic valvular leaflet. Histologically, the arterial end of the In one patient the tunnel closed spontaneously.28 Infective
tunnel resembles the aorta with fibrous tissue, elastic fibers endocarditis has been reported in one case.49
and smooth muscle cells, while the ventricular end contains
hyalinized collagen and muscle. This reflects that the ‘walls’ Clinical Presentation
of the tunnels incorporate the structures through which they
pass.5 The onset, severity and progression of symptoms are variable.
While many patients may have no symptoms, others may pre
Types of Aorto-left Ventricular Tunnel sent with rapid progression or sudden death. Death in utero
may also occur. The symptoms are dependant on the size of
Hovaguimian et al31 have proposed an anatomic classification tunnel, its hemodynamic influence and the associated cardiac
of ALVT based on morphology. They classified them as defects.3 Congestive heart failure may occur at any age due to
Type I A simple tunnel with a slitlike opening at the aortic severe AR.50,51
end and no aortic valve distortion The signs may include bounding pulses, a wide pulse pressure
Type II A large extracardiac aortic wall aneurysm of the and a loud 'to-and-fro' systolic and diastolic murmur. It is usually
tunnel with an oval opening at the aortic end, with or accompanied by systolic and diastolic thrills felt on a wide area on
without ventricular distortion the precordium. In patients with ALVT with pulmonary stenosis,
Type III
Intracardiac aneurysm of the septal portion of the the onset of heart failure is delayed. In those with a tunnel, with
tunnel, with or without right ventricular outflow tract associated severe aortic valve obstruction, heart failure occurs
obstruction early, with or without low cardiac output and nearly one third of
338 Type IV Combination of type II and III reported cases having died before birth or on the first day of life.19
23
Aorticocameral Tunnels
Figure 1: Schematic representation of the most common type of aorto-left ventricular tunnel. The middle figure shows a cross-sectional view at
the approximate level of the aortic sinotubular junction. The tunnel passes from the ascending aorta into the tissue plane between the aortic and
pulmonary roots. (a’) is a longitudinal section across the left ventricular outflow, through the left and right coronary sinuses of Valsalva (plane “a”
of the central figure). In this example, the aortic end of the tunnel lies above the ostium of the right coronary artery, while the ventricular end is
found within the intercoronary, interleaflet triangle. The position of the aortic opening is variable and may be found anywhere above the left or
right coronary sinus, or the intervening commissure. (b’) depicts a longitudinal section crossing the noncoronary and right coronary aortic sinuses
(line “b” in the central figure). Because the pulmonary valve lies distal to the aortic valve, the tunnel may displace the free-standing, muscular,
sub-pulmonary infundibulum enroute to the left ventricular cavity. It does not, however, pass through any ventricular myocardium. Reprinted with
permission from McKay R. Aorto-ventricular tunnel. Orphanet J Rare Dis. 2007;2:41
Diagnostic Methods
the diagnostic investigation of choice.40,53-55 The apical five
Chest X-ray shows cardiac enlargement with uniform chamber view provides the clear anatomic picture of the tun
dilatation of the ascending aorta. The dilated aorta is not nel arising from the aorta (Figures 3A and B). Apical four
infrequently mistaken for the thymus gland. In some patients, chamber view with color Doppler shows the dilated tunnel
the tunnel itself can be seen as a leftward prominence of the entering the RV (Figures 4A and B).
aortic root in the area of the pulmonary trunk.8 The tunnel The subcostal or apical four chamber view can demonstrate
itself can be seen as a right border on chest X-ray in ARVT the device in situ after the transcatheter closure of the tunnel
(Figure 2). The electrocardiogram typically shows left or (Figures 5A and B). The aortic origin of the tunnel as well as its
biventricular hypertrophy with a ‘strain pattern’ of inverted T course and opening into the left ventricle can be demonstrated
waves seen in the precordial leads. The electrocardiogram can in a parasternal long-axis view with color Doppler (Figures 6A
be occasionally normal.52 and B) sometimes with clockwise rotation of the probe.28,56
The two-dimensional transthoracic echocardiography The device in situ can be nicely demonstrated in the same 339
(TTE) with cross-sectional and color Doppler imaging is view (Figure 6C). Tunnels which open into the right ventricle
http://vip.persianss.ir
4
Shunt Defects
A B
Figures 4A and B: Echocardiogram in apical four-chamber view with
color Doppler shows the dilated tunnel entering the right ventricle and
the arrow indicates the extracardiac portion of the tunnel. LA = Left
atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle.
A B
Figures 5A and B: Echocardiogram with color Doppler in the subcostal
view shows no flow in the extracardiac tunnel, with the Amplatzer duct
occluder (device) at the end of the tunnel in the right ventricle with no
residual shunt. LV = Left ventricle; RV = Right ventricle.
Aorticocameral Tunnels
A B C
Figures 6A to C: A. Echocardiogram in parasternal long-axis shows tunnel arising from aorta entering into the left ventricle; B. Color Doppler
shows the course of aorto-left ventricular tunnel; C. Shows the 16 X 14 Amplazter duct occulder (device) in situ in a 4-year-old boy. AO = Aorta;
LA = Left atrium; LV = Left ventricle;
http://vip.persianss.ir
4 Surgery
Aorticocameral Tunnels
A B
C D
Figures 10A to D: A. Transthoracic echocardiography in apical four-chamber view shows aorto-right atrial tunnel in 5 years old boy, draining
into right atrium (RA) with extracardiac portion of the tunnel seen with color Doppler; B. Aortic root angio done in right anterior oblique shows the
aortic tunnel arising from left sinus and draining into RA with extracardiac aneurysmally dilated portion; C. Tortuous extracardiac portion of the
tunnel; D. The guidewire through the tortuous tunnel. AO = Aorta; LA = Left atrium; LV = Left ventricle; RV = Right ventricle.
the high aortic pressure the defective area in the aortic wall 10B). Rupture of sinus of Valsalva can be differentiated
forms an extracardiac tunnel, leading to gradual enlargement by demonstrating a tunnel with an extracardiac course.68
and rupture into the RA because of its anatomic proximity and Aortography also helps to differentiate it from coronary
low filling pressure. cameral fistula and to delineate the tunnel and to assess the
tortuosity and suitability for transcatheter interventions
Symptoms and Signs (Figures 10C and D).
Electron beam tomography or MRA might might
This aorto-right atrial communication behaves like a be additional non-invasive tools for diagnosis. The CT
left-to-right shunt at the atrial level. Most patients may angiography is an additional non-invasive diagnostic tool.
be asymptomatic or they may present with exertional Electron beam tomography can be a good diagnostic tool,
breathlessness, palpitations or recurrent respiratory tract showing the tunnel taking its origin from the aortic root and
infections.72 On physical examination, a continuous murmur entering the right atrium through a tortuous communication.71
at the right parasternal border is present.
Management
Diagnosis
Closure of an aorta-right atrial tunnel is recommended even
The tunnel can be readily identified by TTE. The apical in asymptomatic patients69 as there is only a low rate of
four chamber view shows the tunnel opening into the right procedural complications. Moreover, the continued patency
atrium and the color Doppler also delineates the extracardiac of the tunnel leads to risk for biventricular volume overload,
portion of the tunnel (Figure 10A). Retrograde aortography bacterial endocarditis, pulmonary vascular disease, aneurysm
combined with selective coronary angiography is essential for formation, calcification of the wall, aortic regurgitation and 343
the demonstration of its course and the coronary ostia (Figure spontaneous rupture.67-69,72
http://vip.persianss.ir
4 Treatment options are available according to the type of lian. The Natural and Modified History of Congenital Heart
tunnel/fistula, its caliber, tortuosity, calcification, course and Disease. (Eds) Robert M. Freedom, Shi-JoonYoo, HaverjMi
relation of the coronary ostia to the aortic orifice of the tun kailian. William G Williams Copyright @ 2004 Futura.
Shunt Defects
nel/fistula. They include transcatheter closure, ligation under 5. McKay R. Aorto-ventricular tunnel. Orphanet J Rare Dis.
2007;2:41.
controlled hypotension or repair with the patient under under
6. Edwards JE, Burchell HB. The pathological anatomy of
cardio pulmonary bypass.72,73
deficiencies between the aortic root and the heart, including
Surgical options include plication of the tunnel or patch aortic sinus aneurysms. Thorax. 1957;12:125-39.
closure of aortic origin with direct closure of the atrial 7. Levy MJ, Lillehei CW, Anderson RC, et al. Aortico-left
opening. The ligation for anteriorly located aorta-right atrial ventricular tunnel. Circulation. 1963;27:841-53.
tunnel includes ligation near the aortic end, and for posteriorly 8. Somerville J, English T, Ross DN. Aorto-left ventricular
located tunnels, ligation should be done between between tunnel. Clinical features and surgical management. Br Heart J.
superior vena cava and aorta as close to the aorta as possible.72 1974;36:321-8.
External ligation of the tunnel close to the aorta should be 9. McKay R, Anderson RH, Cook AC. The aorto-ventricular
tunnels. Cardiol Young. 2002;12:563-80.
performed only after accurate evaluation of the external
10. Bharati S, Lev M, Cassels DE. Aortico-right ventricular tunnel.
anatomy and of the relationship between the coronary ostia
Chest. 1973;63:198-202.
and the orifice of the tunnel at the aortic end.74 If the coronary 11. Saylam A, Tuncali T, Ikizler C, et al. Aorto-right ventricular
artery arises from the tunnel, an alternative is to re-implant the tunnel. A new concept in congenital cardiac malformations.
artery as a button into the aortic sinus.71 Ann ThoracSurg. 1974;18:634-7.
Transcatheter treatment is an option in selected cases, 12. Jureidini SB, de Mello D, Nouri S, et al. Aortico-right
where the opening of the right atrial end is small or there is a ventricular tunnel with critical pulmonary stenosis: Diagnosis
constriction in the course of the fistula.72 The appropriate sizes by two dimensional and Doppler echocardiography and
of coils or device can be used. There are a few case reports of angiography. Pediatr Cardiol. 1989;10:99-103.
13. Kleinkamp G, Minami K, Thies WR, et al. Aorta right
transcatheter closure.75,76 However, persistence of the dilated
ventricular tunnel with a rudimentary valve and an anomalous
sinus of Valsalva with transcatheter device closure constitutes
origin of the left coronary artery. J Thorac Cardiovasc Surg.
a concern and demands further follow-up and evaluation for 1992;104:1759-60.
a determination of its evolution.75 Sometimes, if the tunnel is 14. Westaby S, Archer N. Aortico-right ventricular tunnel. Ann
very tortuous the device closure may not be possible. ThoracSurg. 1992;53:1107-9.
15. Rosengart TK, Redel DA, Stark JF. Surgical repair of aorto-
Conclusion right ventricular tunnel in an infant. Ann Thorac Surg. 1993;55:
520-2.
Aorticocameral tunnels are extremely rare congenital cardiac 16. Van Son JA, Hambsch J, Schneider P, et al. Repair of aortic right
ventricular tunnel. Eur J Cardiothorac Surg. 1998;14:214-7.
anomalies. Imaging by TTE and MRI are of great help in
17. Vargas FJ, Molina A, Martinez JC, et al. Aortico-right
diagnosis. Surgical closure of tunnel along with repair of the
ventricular tunnel. Ann Thorac Surg. 1998;66:1793-5.
associated cardiac defects has been achieved with satisfactory 18. Talwar S, Choudhary UK, Kothari SS, et al. Aortico-right
results in the past. Recently, transcatheter closure of tunnels ventricular tunnel. Int J Cardiol. 1999;70:201-5.
with Amplatzer duct occluder, Amplatzer duct occluder II 19. Hruda J, Hazekamp MG, Sobotka-Plojhar MA, et al. Repair of
and coil closures have become a better and more attractive aorto-right ventricular tunnel with pulmonary stenosis and an
alternative to surgery in selected cases without associated anomalous origin of left coronary artery. Eur J Cardiothorac
cardiac defects. Surg. 2002;21:1123-5.
20. Freund MW, Stoutenbeek P, Van der Laan M, et al. Aortico-
right ventricular tunnel. Prenatal diagnosis leading to neonatal
By medicine life may be prolonged, yet death will seize the
survival. Fetal DiagnTher. 2007;22:335-8.
doctor too.
21. Sheikh N. Repair of aorto-right ventricular tunnel: A case
—William Shakespeare report. Cardiovasc J. 2010;3:398-100.
22. Poptani VA, Thakkar BM, Patel NH. Transcatheter closure of a
rare case of aorto-right ventricular tunnel with single coronary
References artery. J Invasive Cardiol. 2010;22:611-4.
23. Lin BS, Zhang XH, Jiang YZ, et al. Diagnosis and surgical
1. Elwatidy AF, Galal AN, Rhydderch D, et al. Aorto-right atrial treatment of adult aortico-right ventricular tunnel. Ann Thorac
fistula. Ann Thorac Surg. 2003;76:929-31. Surg. 2010;89:2024-6.
2. Nihoyannopoulos P, Sapaford R, Oakley CM. Congenital fistula 24. Talwar S, Nair VV, Kothari SS, Gulati GS, Choudhary SK,
between aorta and left atrium. Br Heart J. 1987;57:387-90. Airan B. Aortico- right ventricular tunnel with anomalous right
3. QIU Xing-biao, SHI Hong-yu, LIU Lan, et al. Multiple aortico- coronary artery. J Card Surg. 2011;26:521-6.
cameral tunnels associated with bicuspid aortic valve in aged: a 25. Singh SK, Dwivedi SK, Kumar A, et al. Aneurysmal Aorto-
case report. Chin Med J. 2009;122:2184-5. Right Ventricular Tunnel . Ann ThoracSurg. 2012;93:e21–2.
344
4. Robert M. Freedom and Shi-JoonYoo. Aorto-cameral Commu 26. Vijayalakshmi IB, Chitra N, Ashish A. Closure of Aorto-right
nications in Robert M. Freedom, Shi-JoonYoo, Haverjmikai ventricular tunnel with Amplatzer Duct Occluder II. Accepted
for publication in Journal of Invasive Cardiology on September
21st, 2012.
47. Chen YF, Chiu CC, Wu JR. Correction of aortico-left
ventricular tunnel in a small Oriental infant: a brief clinical
23
27. Turley K, Silverman NH, Teitel D, et al. Repair of aortico- review. J CardiovascSurg (Torino). 1994;35:71-3.
Aorticocameral Tunnels
left ventricular tunnel in the neonate: surgical, anatomic and 48. Grab D, Paulus WE, Terinde R, et al. Prenatal diagnosis of an
echocardiographic considerations. Circulation. 1982;65:1015-20. aortico-left ventricular tunnel. Ultrasound Obstet Gynecol.
28. Martins JD, Sherwood MC, Mayer JE Jr, et al. Aortico-left 2000;15:435-8.
ventricular tunnel: 35-year experience. J Am Coll Cardiol 49. Soulié P, Caramanian M, Pernot JM, et al. Communication
2004;44:446-50. ou tunnel aorto-ventriculaire gauche. [Left aorto-ventricular
29. Cook AC, Fagg NL, Ho SY, et al. Echocardiographic- communication or tunnel]. Arch Mal Coeur Vaiss. 1966;59:
anatomical correlations in aorto-left ventricular tunnel. Br 820-42.
Heart J. 1995;74:443-8. 50. Hucin B, Morvath P, Skovranek J, et al. Correction of aortic
30. Ho SY, Muriago M, Cook AC, et al. Surgical anatomy of aorto- left ventricular tunnel during the first day of life. Ann Thorac
left ventricular tunnel. Ann Thorac Surg. 1998;65:509-14. Surg. 1989;47:254-6.
31. Hovaguimian H, Cobanoglu A, Starr A. Aortico-left ventricular 51. Akalin H, Erd C, Oral D, et al. Aortic left ventricular
tunnel: a clinical review and new surgical classification. Ann tunnel: Successful diagnostic and surgical approach to the
Thorac Surg. 1988;45:106-12. oldest patient in the literature. J Thorac Cardiovasc Surg.
32. Bove KE, Schwartz DC. Aortico-left ventricular tunnel. A new 1989;97:804-5.
concept. Am J Cardiol. 1967;19:696-709. 52. Kafka H, Chan KL, Leach AJ. Asymptomatic aortico-left
33. Levy MJ, Schachner A, Blieden LC. Aortico-left ventricular ventricular tunnel in adulthood. Am J Cardiol. 1989;63:1021-22.
tunnel: collective review. J Thorac Cardiovasc Surg. 1982;84: 53. Perry JC, Nanda NC, Kicks DG, et al. Two-dimensional
102-9. echocardiographic identification of aortico-left ventricular
34. Serino W, Andrade JL, Ross D, et al. Aorto-left ventricular tunnel. Am J Cardiol. 1983;52:913-4.
communication after closure. Late postoperative problems. Br 54. Grant P, Abrams LD, De Giovanni JV, et al. Aortico-left
Heart J. 1983;49:501-6. ventricular tunnel arising from the left aortic sinus. Am J
35. Guyton RA, Michalik RE, McIntyre AB, et al. Aortic atresia Cardiol. 1985;55:1657-8.
and aortico-left ventricular tunnel: successful surgical 55. Humes RA, Hagler DJ, Julsrud PR, et al. Aortico-left ventricular
management by Konno aortoventriculoplasty in a neonate. J tunnel: diagnosis based on two-dimensional echocardiography,
Thorac Cardiovasc Surg. 1986;92:1099-101. color flow Doppler imaging, and magnetic resonance imaging.
36. Bitar FF, Smith FC, Kavey RE, et al. Aortico-left ventricular Mayo Clin Proc. 1986;61:901-7.
tunnel with aortic atresia in the newborn. Am Heart J. 56. Sreeram N, Franks R, Arnold R, et al. Aortico-left ventricular
1993;126:1480-2. tunnel: long-term outcome after surgical repair. J Am Coll
37. Jureidini SB, de Mello D, Norui S, et al. Aortico-right Cardiol. 1991;17:950-5.
ventricular tunnel and critical pulmonary stenosis: diagnosis 57. Biffanti R, Reffo E, Sanders SP, et al. Two-dimensional and
by two-dimensional and Doppler echocardiography and real-time three-dimensional echocardiographic fetal diagnosis
angiography. Pediatr Cardiol 1989;10:99-103. of aorto-ventricular tunnel. Circulation. 2005;111:e367-8.
38. Martin Jimenez J, Gonzales Diegues CC, Quero Jimenez C, et 58. Siepe M, Dittrich S, Beyersdorf F, et al. Aortic atresia with
al. Aortico-left ventricular tunnel associated with pulmonary aortico-left ventricular tunnel mimicking severe aortic incompe
valve stenosis. Rev Esp Cardiol. 1996;49:921-4. tence in utero. Eur J Cardiothorac Surg. 2006;29:845-7.
39. Knott-Craig CJ, van der Merwe PL, Kalis NN, et al. Repair 59. Webber S, Johnston B, LeBlanc J, et al. Aortic-left ventricular
of aortico-left ventricular tunnel associated with subpulmonary tunnel associated with critical aortic stenosis in the newborn.
obstruction. Ann Thorac Surg. 1992;54:557-9. PediatrCardiol. 1991;12:237-40.
40. Bash SE, Huhta JC, Nihill MR, et al. Aortico-left ventricular 60. Tuna IC, Edwards JE. Aortico-left ventricular tunnel and aortic
tunnel with ventricular septal defect: two-dimensional/ insufficiency. Ann Thorac Surg. 1988;45:5-6.
Doppler echocardiographic diagnosis. J Am Coll Cardiol. 61. Grünenfelder J, Zünd G, Prêtre R, et al. Right coronary artery
1985;5:757-60. from aorto-left ventricular tunnel: case report of a new surgical
41. Spooner EW, Dunn JM, Behrendt DM. Aortico-left ventricular approach. J Thorac Cardiovasc Surg. 1998;116:363-5.
tunnel and sinus of Valsalva aneurysm. Case report with 62. Norwicki ER, Abderdeen E, Friedman S, et al. Congenital left
operative repair. J ThoracCardiovasc Surg. 1978;75:232-6. aortic sinus-left ventricle fistula and review of aortocardiac
42. McKay R. Invited commentary. Ann Thorac Surg 1992;54:559. fistulas. Ann Thorac Surg. 1997;23:378-88.
43. Bonnet D, Bonhoeffer P, Sidi D, et al. Surgical angioplasty of 63. Chessa M, Chaudhari M, De Giovanni JV. Aorto-left ventricular
the main coronary arteries in children. J Thorac Cardiovasc tunnel: transcatheter closure using an amplatzer duct occluder
Surg. 1999;117:352-7. device. Am J Cardiol. 2000;86:253-4.
44. Horváth P, Balaji S, Škovránek S, et al. Surgical treatment 64. Vijayalakshmi IB, Chitra N, Prabhu Deva AN. Use of an
of aortico-left ventricular tunnel. Eur J Cardiothorac Surg. Amplatzer duct occluder for closing an aortico-left ventricular
1991;5:113-7. tunnel in a case of noncompaction of the left ventricle. Pediatr
45. Rauzier JM, Bonnet D, Zniber L, et al. Aortico-ventricular Cardiol. 2004;25:77-9.
tunnel with right coronary artery atresia. Arch Mal Coeur 65. Archer TP, Mabee SW, Baker PB, et al. Aorto-Left atrial
Vaiss. 1997;90:725-7. fistula. A reversible cause of acute refractory heart failure.
46. Sousa-Uva M, Touchot A, Fermont L, et al. Aortico-left Chest. 1997;111:828-31.
345
ventricular tunnel in fetuses and infants. Ann Thorac Surg. 66. Patsouras D, Argyri Q, Siminilakis S, et al. Aortic dissection
1996;61:1805-10. with aorto-left atrial fistula formation soon after aortic valve
http://vip.persianss.ir
4 replacement: A lethal complication diagnosed by transthoracic
and transesophageal echocardiography. J Am SocEchocardiogr.
72. Gajjar T, Voleti C, Matta R, et al. Aorta right atrial tunnel:
clinical presentation, diagnostic criteria, and surgical options. J
2002;15:1409-11. Thorac Cardiovasc Surg. 2005;130:1287-92.
Shunt Defects
67. Otero-Coto E, Caffarena JM, Such M, et al. Aorta-right atrial 73. Aggarwal SK, Sai V, Iyer VR. Imaging features of aorto-right
communication: report of an unusual case. J Thorac Cardiovasc atrial tunnel: a report of two cases. Congenit Heart Dis. 2007;2:
Surg. 1980;80:941-4. 429-32.
68. Rosenberg H, Williams WG, Trusler GA, et al. Congenital 74. Moraes F, Santos CL, Moraes CR. Aortic-right atrial tunnel.
aortico–right atrial communications. J Thorac Cardiovasc Cardiol Young. 2004;14:86-8.
Surg. 1986;91:841-7. 75. Chandra S, Vijay S, Kaur D, et al. Congenital aorta right atrial
69. Kalangos A, Beghetti M, Vala D. Aortico-right atrial tunnel. fistula: successful transcatheter closure with the Amplatzer
Ann Thorac Surg. 2000;69:635-7. occluder. Pediatr Cardiol. 2011;32:1057-9.
70. Ooman A, Mao R, Krishnan P, et al. Congenital aortocaval 76. Kappanayil Mahesh, Edwin Francis, and Raman Krishna
fistula to superior vena cava. Ann Thorac Surg. 2000;72:91-3. Kumar. Aorta to Right Atrial Tunnel: Prenatal Diagnosis and
71. Turkay C, Golbasi I, Belgi A, et al. Aorta–right atrial tunnel. J Transcatheter Management in a Neonate J. Am Coll Cardiol
ThoracCardiovasc Surg. 2003;125:1058-60. Intv. 2008;1:716-7.
346
C hapter
Introduction are often associated with prolapse of aortic cusps and aortic
incompetence. Coarctation of the aorta, atrial septal defect,
The sinuses of Valsalva are three small outpouchings in the tetralogy of Fallot and patent ductus arteriosus also may be
wall of the aorta immediately above the attachments of each associated with these aneurysms.5
aortic cusp. First report of ruptured sinus of Valsalva was Most aneurysms are single and most commonly affect
published in 1839 by Hope.1 Thurnam named the sinuses the right coronary aortic sinus. Two-thirds of the aneurysms
according to their relationship to the coronary arteries as are located in the right aortic sinus, one-fourth in the non-
the right coronary sinus, the left coronary sinus and the non- coronary sinus and the rest in the left aortic sinus.9
coronary sinus.2 Aneurysms of the right coronary aortic sinus usually
Aneurysm of sinus of Valsalva (ASV) accounts for 1 prolapse into the right ventricle or right atrium and those from
percent of congenital anomalies of the heart and circulation.3 the non-coronary sinus into the right atrium. Aneurysms of the
The aneurysms tend to be single although exceptionally more left coronary aortic sinus prolapse into the left ventricle.10,11
than one sinus is involved.4-7 Rupture can also occur through the septal leaflet of the
The incidence varies from 0.14 to 0.35 percent.4 The tricuspid valve, producing an acquired atrioventricular septal
prevalence is more in Asian population compared to Western defect.10 There is an increased incidence of rupture when
world.7 The developmental fault is at the junction of the aortic an aneurysm occurs in the presence of a doubly committed
media and the annulus fibrosis and sets the stage for avulsion subarterial ventricular septal defect. Rupture in these cases
and aneurysm formation.8 Rupture is rare in infancy and occur into the right ventricular outflow tract. Rarely, rupture is
childhood, being more commonly seen in adults. into the pulmonary artery,12-14 left ventricle,15-17 left atrium17
or pericardial cavity.18,19 Also rarely, a sinus aneurysm dissects
PATHOLOGY into the interventricular septum and either remains unruptured
or perforates into the left or right ventricle.15,20 Box 1 depicts
Mural weakness of aortic sinuses causes congenital aneurysm the working classification of ASV.17
of the sinuses, which produces downward prolapse of the A large unruptured aneurysm may compress the superior
leaflets. The dilated sinus may bulge into an atrium or ventricle vena cava, right atrium, right ventricle21,22 or a coronary
and may rupture. artery23,24 or may cause aortic regurgitation by interfering
Aneurysms can be congenital or acquired after bacterial with coaptation of aortic leaflets.25,26 A rare case of unruptured
endocarditis (BE). The BE can also occur on congenital aneurysm of both right and left sinuses causing right ventricular
aneurysms. Sometimes, it becomes difficult to identify ouflow tract (RVOT) and left ventricular outflow tract (LVOT)
whether BE is the effect or cause of the aneurysm rupture. obstruction and burrowing into interventricular septum, which
Rupture has been reported in Behçet disease and may also does not fit into any classification is reported (Figures 1
occur long time after repair of aortic dissection. and 2).27 The congenital etiology of an aortic sinus aneurysm is
In 30 to 50 percent cases, congenital aneurysms are debatable if it originates in the left coronary sinus and ruptures
associated with ventricular septal defect (VSD) especially into the left side of heart.17,28 At surgery most fistulas resemble
defects of the outlet septum. Proportion of VSD is higher windsocks projecting from the sinus into the chamber of entry,
with aneurysms of right aortic sinus. Subpulmonic VSDs with one or more openings near the end of the windsock.
http://vip.persianss.ir
4 Box 1: Sakakibara and Konno’s
classification of ASV17
Shunt Defects
http://vip.persianss.ir
4 venous congestion without increased pulmonary arterial 1. Root of the aneurysm above the aortic annulus.
blood flow and with a selective increase in left ventricular 2. Saccular-shaped aneurysm.
size. Rarely, calcium is deposited in the aortic sinus aneurysm. 3. Normal size of aorta above the aneurysm.
Shunt Defects
Occasionally right or left aortic sinus aneurysm may project 4. Continuous systolic and diastolic turbulence detected by the
out as dense convex paracardiac shadow.49 pulsed wave Doppler just distal to the area of perforation at
Transthoracic echocardiography (TTE) can detect the ASV high velocities.
(Figure 4). 2D echocardiography with color flow imaging and 5. Color flow mapping with mosaic turbulence across the
Doppler identifies the ruptured or unruptured aneurysm, the perforated aneurysm in real time.
chamber receiving the shunted blood, volume overloading of Ischemic left ventricular regional wall motion abnormalities
the heart, associated defects and degree of aortic regurgitation caused by compression of the coronary artery origins by the
(Figures 5A and B). Unruptured defects are characterized aneurysm are evident on real time screening.
by phasic expansion and relaxation and to-and-fro pulsed Non-invasive imaging with computed tomography or
Doppler signals at the site of origin from the aorta, but no magnetic resonance scans have been shown to provide
color flow evidence of rupture. Echocardiographic diagnostic excellent definition of the aneurysm and the tissue planes
criteria50 include: involved.51
MANAGEMENT
The conventional treatment of these aneurysms has
been surgical repair with patch closure at both ends
under cardiopulmonary bypass. A simple and functional
classifcation system by Vural et al52 can be used as a guideline
for the therapeutic approach to ASVs, based on the clinical
picture and the echocardiographic findings (Figure 6). The
indication for surgery is for both ruptured ASV (Type A) and
for symptomatic unruptured ASV (Type B-II). The size of the
aneurysm detemines the indication for surgical intervention
in unruptured asymptomatic ASV (Type B-I). Surgical
treatment is necessary, if the size of the aneurysm is larger
than 50% of the average size of the other two normal Valsalva
sinuses or is increasing in consecutive echocardiographic
examinations. In addition, patients should be operated on if
there is compression or malformation of the adjacent tissues.
Figure 4: Transthoracic echocardiography (TTE) in parasternal Surgery is indicated for the extracardiac type of ASV (Type C).
short-axis shows aneurysm of the sinus of Valsalva
Although, the mortality is low (< 2%), the potential morbidity
from cardiopulmonary bypass and thoracotomy including the
scar are the underlying hazards. Although the long-term result
of the successful repair is usually good, residual shunt may
require reoperation, which carries a high mortality.53
The first percutaneous intervention for a shunt of this
kind was attempted by Hourihan et al in 1992 for acquired
arteriovenous fistula after aortic valve replacement.54 In 1994,
Cullen described closure of recurrent left-to-right shunt after
surgical repair of perforated congenital sinus of Valsalva
aneurysm, with Rashkind umbrella device.55
In the present era, ruptured aortic sinus aneurysm can
be closed percutaneously with device after careful patient
selection. Patient with left-to-right shunt with pulmonary to
systemic flow ratio of greater than 1.5:1 with right ventricle
A B
volume overload greater than 1.5 cm/m2 and the margin of the
Figures 5A and B: A. Transthoracic echocardiogram (TTE) in defect at least 5 mm from the right coronary ostia are suitable
parasternal long-axis view shows non-compaction of of left ventricle for device closure.56 Device closure of the defect has been
with subaortic ventricular septal defect. B. TTE in parasternal long-axis
view with color Doppler shows rupture of aneurysm of sinus of Valsalva
shown to be a safe and effective alternative to surgery on short-
350 term follow-up of a small series of patients.57
into right ventricle and aortic regurgitation jet into left ventricle.
24
A B
Figures 7A and B: A. Aortic root angiogram shows opacification of right ventricle (RV) through rupture of sinus of Valsalva (RSOV);
B. Aortic root angiogram after device closure shows 8 x 6 duct occluder (device) in situ with no residual flow
Defects are usually closed with Amplatzer duct occluder After establishing femoral artery and venous access, intra
(ADO). The selected size of ADO should be 1 to 2 mm greater venous antibiotics and heparin is given at 100 mg/kg, right
than the measured defect size (Figures 7A and B). and left heart catheterization is done, and direct pulmonary
The procedure is performed under local anesthesia with artery pressure is measured. Coronary angiography is
fluoroscopic and transthoracic/transesophageal echocardio- performed to document coronary arteries anatomy and their
graphic guidance. Some centers prefer general anesthesia for distance from the defect before closure is attempted. Aortic 351
the procedure. root cine-angiogram is performed in at least two orthogonal
http://vip.persianss.ir
4 views to define the opening of the wind sock defect and its infusing antegrade cold cardioplegia through the coronary
size. ostia directly. The orifice of the RSOV is visualized and
The defect is then crossed with a multipurpose or a right the VSD if present is visualized by lifting the aortic cusp.
Shunt Defects
coronary catheter from the left ventricle to the right ventricular Redundancy or cusp prolapse is noted.
side. As the defect is crossed with the catheter, an exchange Repair of RSOV can be attempted through right atrium
length Terumo wire is advanced through the catheter across or right ventriculotomy. The thin windsock, which is the
the defect and is kept into the superior vena cava or the aneurysmal sac with a single opening or multiple perforations
pulmonary artery and snared from there and taken out from is excised, creating a large defect in the right sinus, which is
the femoral vein forming an arteriovenous circuit. down stream or cephalad to the VSD, separated by a hinge
Subsequently, an appropriate sized device is advanced line of the aortic cusp. Dacron or polytetrafluoroethylene
via a Mullins sheath from the femoral venous side and is (PTFE) patch is sewen to close the VSD and the defect in the
advanced into the ascending aorta. With the distal device end sinus of Valsalva, taking care to suture the aortic cusp hinge
open the whole assembly is then withdrawn to the opening to the patch at appropriate level. The ventriculotomy or atrial
of the defect on the aortic side. An aortography is then opening is closed with continuous polypropylene suture.
performed to check the position of the device and residual The aortic valve cusps are inspected and any cuspal
shunt. Simultaneously the device position is checked by redundancy or prolapse is addressed by performing a Trusler
transesophageal echocardiography and once satisfied with repair. If valve cusps are not suitable for repair, aortic valve
the position, the device is then deployed within the defect. may have to be replaced.
Selective coronary angiography may also be performed to rule The RSOV can be repaired through aorta or pulmonary
out any encroachment of the device.56 artery or right atrium. The approach could be through aorta or
Gianturco-Grifka vascular occlusion device is another right atrium alone if there is no associated VSD.
alternative from the venous route. Patients should receive anti
coagulant prophylaxis and infective endocarditis prophylaxis CONCLUSION
for 6 months after the procedure.
Device closure should not be attempted in patients with Aneurysm of the sinus of Valsalva is an uncommon disorder,
an aneurysm which has ruptured into the pulmonary artery most commonly presenting subsequent to rupture into a
and left ventricle, presence of associated lesions such as as cardiac chamber. The ruptured sinus of Valsalva is usually
VSD and aortic regurgitation, aneurysmal opening within 5 acquired later in life, usually with no history of heart disease.
mm of coronary ostia, right-to-left shunting across the defect It can occur spontaneously, following chest wall trauma or an
with systemic saturation less than 94 percent, patients with episode of bacterial endocarditis. The onset is usually sudden
pulmonary vascular resistance greater than 7 Wood units and or acute with a loud continuous murmur and often associated
significant right ventricle/left ventricle dysfunction with left with significant congestive heart failure. The timely surgical
ventricular ejection fraction less than 30 percent.58 closure or transcatheter device closure can reduce the
morbidity and mortality.
Surgical Management of Rupture of Sinus of Valsalva
People pay the doctor for his trouble; for his kindness they
A diagnosis of RSOV requires surgical intervention to still remain in his debt.
prevent progression of the disease resulting in death from —Seneca
right heart failure. There are many variants of RSOV,
which may require a specific technique to repair the defect. acknowledgment
However, the basic technique remains the same. Excision
of windsock, patch closure of RSOV, VSD closure if We express our thanks to Dr IB Vijayalakshmi, Professor of
present and an aortic valve repair or replacement for aortic Pediatric Cardiology, for providing all the illustrative images
regurgitation. for this chapter.
Initial preparation (CPB) is as for any open-heart
procedure. After midsternotomy, pericardium is opened and REFEReNCES
an external evaluation is done. There are no external evidence
of aneurysm. The sac of aneurysm may be palpated through 1. Hope J. A Treatise on the Diseases of the Heart and Great
the freewall of the right ventricle. Vessels, 3rd edition. J Churchill and Sons London, 1839.
Cardiopulmonary bypass is established after cannulation 2. Walmsley T. The heart. In Quain’s Elements of Anatomy, Volume
4. Part New York: Longmans, Green and Company, 1929.
of ascending aorta and direct caval cannulation.With mild-to-
3. Wells T, Byrd B, Neirste D, et al. Images in cardiovascular
moderate hypothermia, aorta is cross clamped, right atrium medicine. Sinus of valsalva aneurysm with rupture into the
opened and a vent suction introduced through foramen interventricular septum and left ventricular cavity. Circulation.
352 ovale.Aorta is opened transversly, cardiac arrest achieved by 1999;100:1843-84.
4. Chamsi-Pasha H, Musgrove C, Morton R. Echocardiographic
diagnosis of multiple congenital aneurysms of the sinus of
diagnosed by two-dimensional and Doppler echocardiography.
J Am Coll Cardiol. 1986;7:438-41.
24
Valsalva. Br Heart J. 1988;59:724-6. 25. Rubin DC, Carliner NH, Salter DR, et al. Unruptured sinus
http://vip.persianss.ir
4 45. Channer KS, Hutter JA, George M. Unruptured aneurysm of
the sinus of Valsalva presenting with ventricular tachycardia.
52. Vural K, Sener E, Taşdemir O, et al. Approach to sinus of
valsalva aneurysm:a review of 53 cases. Eur J Cardiothorac
Eur Heart J. 1988;9:186-90. Surg. 2001;20:71-6.
Shunt Defects
46. Kieffer SA,Winchell P. Congenital aneurysms of the aortic 53. Dong C, Wu QY, Tang Y. Ruptured sinus of valsalva
sinuses with cardioaortic fistula. Dis Chest. 1960;38:79-96. aneurysm: a Beijing experience. Ann Thorac Surg.
47. Ramsey TL, Mosquera VT. Ruptured congenital aneurysm of 2002;74:1621-4.
the sinus of Valsalva with superimposed endocarditis; rupture of 54. Hourihan M, Perry SB, Mandell VS, et al. Transcatheter
aortic cusp producing sudden death. Ohio Med. 1946;42:843-5. umbrella closure of valvular and paravalvular leaks. J Am Coll
48. Buzzi A. Evaluation of a precordial continuous murmur. Cardiol. 1992;6:1371-7.
Rupture of aneurysm of sinus of Valsalva into the right 55. Cullen S, Somerville J, Redington A. Transcatheter closure
ventricle. Am J Cardiol. 1959;4:551-3. of a ruptured aneurysm of the sinus of Valsalva. Br Heart J.
49. Reid PG, Goudevenos JA, Hilton CJ. Thrombosed saccular 1994;71:479-80.
aneurysm of a sinus of Valsalva: unusual cause of a mediastinal 56. Arora R. Catheter closure of perforated sinus of Valsalva.
mass. Br Heart J. 1990;63:183-5. In: Sievert H, Qureshi SA, Wilson N, Hijazi ZM (Eds).
50. Dev V, Shrivastava S. Echocardiographic diagnosis of Percutaneous Interventions for Congenital Heart Disease.
unruptured aneurysm of the sinus of Valsalva dissecting into Informa Healthcare, London; 2007. pp. 257-62.
the ventricular septum. Am J Cardiol. 1990;66:502-3. 57. Sen S, Chattopadhyay A, Ray M, et al. Transcatheter device
51. Noji Y, Hifumi S, Nagayoshi T, et al. Sixteen-slice computed closure of ruptured sinus of valsalva: Immediate results and
tomography, transthoracic real-time 3-dimensional echocardio short term follow up. Ann Pediatr Cardiol. 2009;2:79-82.
graphy and magnetic resonance imaging assessment of a long- 58. Arora R, Trehan V, Rangashetty UM, Mukhopadhyay S,
term survivor of rupture of sinus of valsalva aneurysm. Intern Thakur AK, Kalra GS. Transcatheter closure of ruptured sinus
Med. 2005;44:513-5 of valsalva. J Interv Cardiol. 2004;17:53-8.
354
Sec t i on
http://vip.persianss.ir
C hapter
Suresh Kumar R
The right ventricular outflow tract (RVOT) may be deemed to Clinical Features
commence at the infundibulum and to comprise the pulmonary
valve and the pulmonary arterial tree. The obstruction of this Valvar pulmonary stenosis has distinctive clinical features
region are discussed under the following headings: based on the age of presentation. Hence, clinical features may
1. Pulmonary valve stenosis. be described as for the neonate, child and adult.
2. Infundibular stenosis.
3. Double-chambered right ventricle. Valvar Pulmonary Stenosis in the Neonate
4. Peripheral pulmonary artery stenosis.
Critical valvar pulmonary stenosis in the neonate presents
VALVAR PULMONARY STENOSIS dramatically with profound hypoxia. The term critical
pulmonary stenosis with intact ventricular septum is applied
Isolated pulmonary valvar stenosis is an acyanotic malforma to severe pulmonary valvar stenosis resulting in systemic/
tion with normal or diminished pulmonary blood flow. The suprasystemic right ventricular pressures and right to left
ventricular septum is intact in 80 percent of cases. The first shunt across the atrial septum, often with significant tricuspid
description of this malformation was given by Morgagni in regurgitation. The pulmonary flow may be completely duct
1761.1 dependent—‘functional pulmonary atresia’. The affected
neonate has cyanosis, congestive heart failure, hypotension,
Incidence feeding difficulty and tachypnea. On clinical examination,
there is no impressive murmur quite often. The pulmonary
Stenosis of the pulmonary valve represents 8 to 12 percent component of the second sound is delayed, soft or absent.
of all congenital heart defects in children2,3 and 15 percent There may be a pansystolic murmur of tricuspid regurgitation.
of all congenital heart defects in adults.4-6 Isolated valvar Milder stenosis is asymptomatic and is characterized by the
pulmonary stenosis with an intact ventricular septum is the phasic ejection click and ejection systolic murmur, once the
second most common congenital cardiac defect in children of pulmonary vascular resistance has fallen. Two-dimensional
the United States. It occurs with equal incidence in both the (2D) echocardiography is diagnostic for this condition.
sexes.6
Valvar Pulmonary Stenosis in Children
Genetics
Valvar pulmonary stenosis is generally well tolerated and even
Non-syndromic pulmonary valve stenosis is an isolated severe stenosis is often asymptomatic. General examination is
lesion, even though autosomal dominant inheritance has unremarkable, though atypical moon-like facies and chubby
been reported in some families.7 Syndromes associated with cheeks have been described.6 Jugular venous pressure (JVP)
valvar pulmonary stenosis include Noonans’ syndrome, shows prominent ‘a’ waves in severe stenosis. Apex beat is
Williams’ syndrome, rubella syndrome, Leopard syndrome normal. A left parasternal heave represents severe stenosis.
and cardiofacial syndrome. Seven percent of children The second heart sound is often widely split with P2 well
with pulmonary stenosis have Noonans’ syndrome.8 The preserved in milder stenosis. The auscultatory hallmark of
critical region for Noonans’ syndrome type-1 is located on valvar pulmonary stenosis is the phasic ejection click. This
chromosome 12 q24. click is characteristically louder in expiration, representing
http://vip.persianss.ir
5 the greater range of mobility the valve has in this phase of Echocardiogram
respiration. The click moves closer to the first sound as the Two-dimensional echocardiography is the best diagnostic
stenosis progresses and eventually appears to merge with it. In modality for assessment of pulmonary valve anatomy,
Right and Left Ventricular Obstructive Lesions
severe pulmonary stenosis, the S1 appears to be accentuated localization of stenosis and evaluation of right ventricular size
in expiration in the pulmonary area, due to the fused click. A and function. Typical valvar stenosis is characterized by mildly
harsh ejection systolic murmur, often associated with a thrill thickened leaflets that dome in systole.15 Presystolic doming
in the left upper sternal border is characteristic of pulmonary of the valve may be seen during atrial contraction in patients
stenosis. A long murmur with delayed peak characterizes with severe stenosis and a non-compliant right ventricle.15
severe pulmonary stenosis. Truly dysplastic valves are characterized by markedly
thickened and seemingly immobile leaflets, small valve
Valvar Pulmonary Stenosis in Adults annulus and often supravalvular narrowing.16 It is important
to identify dysplastic valves, as balloon valvuloplasty in these
Survival into adulthood may occur in many uncorrected patients patients may achieve only suboptimal results. Continuous
with pulmonary stenosis. Fibrous thickening and occasionally wave Doppler measurement of peak systolic velocities
calcification of the valve occurs with age. Clinical features estimates the transpulmonic gradient, which is comparable
vary from mild exertional dyspnea to signs of right heart to values obtained at cardiac catheterization.17,18 The severity
failure. Moderate to severe obstruction leads to inability to is typically defined by the peak systolic gradient across the
augment pulmonary blood flow during exercise, resulting in pulmonic valve.19 Values less than or equal to 40 mm Hg
fatigue, syncope or chest pain. Adults with mild or moderate denote mild stenosis, while values more than equal to 80
pulmonary stenosis have findings similar to those described in mm Hg denote severe stenosis. However, in the outpatient
children. Severe pulmonary stenosis may present with features setting, values above 64 mm Hg may be considered to indicate
of right heart failure. JVP is elevated with prominent ‘a’ waves. moderate stenosis warranting intervention.
Cardiomegaly is common. Second heart sound is widely split, Color Doppler is particularly useful to identify the jet
the pulmonary component is often inaudible. Right ventricular width of severe pulmonary stenosis and to identify ductal
third and fourth heart sounds are heard. The murmur has flow. However, pulmonary regurgitation can also be detected
the characteristics already described. However, the tricuspid and quantitated.20
regurgitation murmur may overshadow the clinical presentation.
Management
Investigation
Children with mild pulmonary stenosis do not need intervention
in childhood.21 They should be clinically followed yearly.
Electrocardiogram
Limitations in exercise or activity levels are not needed.
Baseline electrocardiogram (ECG) is usually normal in mild Infective endocarditis prophylaxis is indicated during surgery
to moderate pulmonic stenosis.9 In more severe cases, right or any procedure likely to produce bacteremia.
atrial enlargement, right ventricular hypertrophy and right Patients with moderate to severe pulmonary stenosis
axis deviation are observed. Incomplete right bundle branch (Doppler gradient ≥ 64 mm Hg) should undergo intervention.
block (RBBB) may be seen. Left bundle branch block (LBBB) After the obstruction is relieved, routine care and endocarditis
and left axis deviation point to Noonans’ syndrome.10 The ‘T’ prophylaxis are recommended as in the case of mild
wave may be upright or inverted with occasional ST segment stenosis.
changes suggestive of ischemia.11 For patients between 2 Patients with signs of right ventricular failure should be
and 20 years, the resting right ventricular pressure can be treated with decongestive measures followed by intervention
calculated from the ECG using the following formula.12 to relieve the obstruction. The right ventricular function may
Right ventricular (RV) pressure in mm Hg = R wave length not recover completely in adults.
(mm) in V1 × 5.
Balloon Pulmonary Valvuloplasty
Chest Radiogram
Currently, balloon valvuloplasty is the treatment of choice for
In mild to moderate pulmonary stenosis, the heart size managing isolated pulmonary valve stenosis.22,23 Jean S Kan
and pulmonary vascular markings are normal. The most reported the first case of balloon pulmonary valvuloplasty in
distinctive feature is a prominent main pulmonary artery 1982.24
segment secondary to poststenotic dilatation of the pulmonary
trunk and the proximal part of the left pulmonary artery—seen Indications
in 90 percent of patients. Poststenotic dilatation may be absent
358 in infants, small children and in patients with dysplastic 1. Neonates with critical pulmonary stenosis (severe
pulmonary valve as in Noonan’s syndrome.13,14 pulmonary stenosis with systemic desaturation).
2. Infants or older children a peak-to-peak catheter gradient disturbing the wire position. Right ventricular pressure 25
or echocardiographic peak instantaneous gradient of > less than half-systemic levels denote good result. If the
40 mm Hg or clinically significant pulmonary valvar right ventricular pressure is more than the desired level, it
Surgical Technique
The currently preferred technique for valvar pulmonary
stenosis is transpulmonary arterial valvotomy under cardio
pulmonary bypass.40
Indications
1. Dysplastic pulmonary valve with valve ring hypoplasia.
Figure 1: Valvar pulmonary stenosis. Right ventricular angiogram in 2. Fixed infundibular and supravalvar stenosis with pulmonary
lateral view. Note the doming pulmonary valve valvar stenosis. 359
http://vip.persianss.ir
5 Isolated Infundibular Stenosis and lateral projections demonstrate the site of infundibular
obstruction well. The narrowing is more during systole, with
Infundibular stenosis commonly occurs in association with a normal pulmonary valve and no poststenotic dilatation of the
Right and Left Ventricular Obstructive Lesions
malaligned ventricular septal defect (VSD) in the setting of main pulmonary artery. The treatment of significant primary
tetralogy of Fallot (TOF). Isolated infundibular stenosis with infundibular stenosis is surgical resection of the fibrotic area
intact ventricular septum is a very uncommon defect, initially or hypertrophic muscle.
described by Elliotson in 1830. It accounts for 5 percent of all
cases of RVOT obstruction. It is of two types41 Double-Chambered Right Ventricle
1. A fibrous band at the junction of the infundibulum and cavity
of the right ventricle (Figure 2). This is the more common Double-chambered right ventricle (DCRV) is a distinctive
type resembling double-chambered right ventricle. anatomic entity, wherein there is a muscular obstruction
2. Fibromuscular obstruction directly below the pulmonary below the infundibulum dividing the right ventricle into a low
valve. pressure infundibulum and a high pressure apical portion.
The proposed embryologic abnormality is an arrest of Anderson has provided an elegant description of the
bulbus cordis involution during the development of the pathologic anatomy of this entity.42 The septal band of the
outflow tract. septomarginal trabeculation is a prominent muscular shelf on
The physical findings consist of a loud, systolic ejection the septal surface of the right ventricle, from where a series
murmur with a widely split second sound and soft pulmonary of muscle bundles extend to the free wall as septoparietal
component. Two findings that help to distinguish infundibular trabeculations—the most prominent one going to the anterior
from pulmonary valve stenosis are the relatively lower papillary muscle as the moderator band. The obstructive
location of the murmur at the lower sternal border and the muscle bundles of DCRV are abnormally hypertrophied septo-
absence of an ejection click. The ECG features are similar parietal trabeculations extending towards right ventricular
to those of pulmonary valve stenosis. The X-ray findings are apex. Two characteristic locations of obstruction include:
not distinctive. Echo-Doppler studies help in distinguishing a. Low oblique one close to the apex.
infundibular from valvar stenosis. Systolic fluttering of b. Higher horizontal one close to the infundibulum.
the pulmonary valve, as against doming, is the hallmark of The right ventricular inlet continuous with the apical
subvalvular obstruction. The severity of the obstruction can trabecular portion has a higher pressure and the infundibular
be estimated by continuous wave Doppler. Selective right chamber has a lower pressure.
ventriculogram in right anterior oblique (RAO) cranial
Prevalence
Double-chambered right venticle cardiac defect typically
presents in infancy and childhood. Ten percent of children
undergoing correction of VSD and TOF may have associated
DCRV.43 There are isolated reports in adults.44
Associated Anomalies
The DCRV is seldom seen as an isolated anomaly. Most
commonly it is associated with a perimembranous VSD. Other
lesions include subaortic stenosis, pulmonary valve stenosis,
double outlet right ventricle,45 TOF, anomalous pulmonary
venous drainage, complete or corrected transposition of
the great arteries, pulmonary atresia with intact ventricular
septum and Ebstein anomaly.
Clinical Features
Patients with isolated DCRV and mild to moderate
right ventricular outflow tract obstruction (RVOTO) are
Figure 2: Right ventricular (RV) angiogram in AP with 10° right anterior asymptomatic. When RVOTO is severe, exertional fatigue,
oblique view illustrates highly trabeculated RV with hypertrophied dyspnea, light headedness, or chest discomfort (right
bands causing isolated infundibular stenosis (arrows) in 8 years old girl.
INF = infundibulum; MPA = Main pulmonary artery; RV = Right ventricle
ventricular angina), may be experienced.45 The variability
360 of presentation is in part attributable to the multiplicity of
Image Courtesy: Dr IB Vijayalakshmi
associated lesions. If there is an interatrial communication severe forms, the obstruction is seen as a pyramidal filling 25
or if the VSD is proximal to the obstruction cyanosis may defect, with its base broadly attached to the anterior ventricular
occur. Severe RVOTO results in RV heave. The ejection wall and with the apex protruding superiorly47 (Figure 3A). In
Electrocardiogram
The ECG usually shows RV hypertrophy and right axis
deviation, but may have atypical features like dominant
R in lead V4R, with only an rS complex in V1. These
electrocardiographic abnormalities are attributed to the
absence of hypertrophy of the distal right ventricular chamber.
Chest X-ray
Radiologic findings may vary from a small heart with decreased
vascularity to cardiomegaly with increased vascularity of the
lungs, depending on the presence of a large left to right shunt
or RV dysfunction.
2D Echo
The best view for diagnosing DCRV is the subcostal short- A
axis view in infants and young children.43,46 In older patients,
the parasternal short-axis view at the level of the aortic valve
is useful.4 An anomalous bundle is identified, just below the
ostium of right ventricular infundibulum in the short-axis
view.5 The distal portion of the infundibulum located under the
pulmonary valve is wide open and free of obstruction. The exact
site of obstruction could be identified on color flow Doppler.2
Associated lesions like VSD may be recognized. Care is needed
not to mistake the systolic jet of a VSD from that resulting due
to the obstruction within the ventricular cavity.6
Transesophageal echo would allow better definition of the
lesion in adults.
Cardiac Catheterization
The pressure data characteristically shows a low pressure
tracing in the pulmonary artery, as well as the infundibular
chamber, while the pressure is high (often suprasystemic)
in the RV apex. Angiocardiography in RAO/AP and lateral B
views is the ideal diagnostic technique in cases of DCRV.7 Figures 3A and B: A. Double-chambered right ventricle. Right
The anomalous muscle bundles in anteroposterior projection ventricle (RV) angiogram in anteroposterior view showing severe
sub-infundibular stenosis and the pyramidal filling defect with its base
take the form of one or more filling defects that cross the right
towards anterior RV wall; B. Double-chambered right ventricle. Same 361
ventricular cavity either diagonally or horizontally. In most findings in lateral view
http://vip.persianss.ir
5 Pulmonary Artery Stenosis – Reimplantation of pulmonary artery (truncus
arteriosus, aortopulmonary collaterals)
The word pulmonary artery stenosis refers to obstruction – Pulmonary arterioplasty
Right and Left Ventricular Obstructive Lesions
anywhere in the area from the main pulmonary artery and – Fibrosing mediastinitis
its branches to the distal intrapulmonary arteries. The term – Mediastinal tumor
peripheral pulmonary artery stenosis has generally been used – Takayasus’ arteritis.
synonymously. The word supravalvar pulmonary stenosis has
been used to describe main pulmonary artery (MPA) stenosis. Clinical Features
Gay and Smith have classified peripheral pulmonary artery
stenosis into four types (Figure 4): The diverse etiology of pulmonary artery stenosis makes
1. Proximal main pulmonary artery stenosis. difficult the prediction of an incidence figure. The disease
2. Bifurcation stenosis. may manifest itself at any age from neonatal period to late
3. Distal pulmonary artery stenosis. adulthood. Diffuse peripheral pulmonary artery stenosis
4. Combination of multiple levels of stenosis. can present with life threatening central pulmonary artery
hypertension in the neonatal period. Postoperative pulmonary
Causes artery stenosis may manifest at any age from immediate
post operative period to late adulthood. Discrete pulmonary
1. Congenital artery branch stenosis is usually asymptomatic, but may
• Ductal constriction worsen pulmonary regurgitation in a repaired TOF and cause
• tof congestive heart failure. Central pulmonary artery stenosis,
• Pulmonary atresia/VSD/major aortopulmonary collateral bilateral pulmonary artery stenosis or diffuse peripheral
arteries (MAPCAs) pulmonary artery stenosis may elevate central pulmonary
• Alagille syndrome artery and right ventricular pressure.
• William-Beuren syndrome Clinical examination reveals characteristic dysmorphic
• Noonan’s syndrome features in situations like Noonan’s syndrome or Williams
• Congenital rubella syndrome syndrome. Cyanosis may occur if right ventricular pressure
• Cutis laxa is high and a PFO is shunting right-to-left. JVP may
• Ehlers-Danlos syndrome show prominent ‘a’ waves. Left parasternal heave may be
• Silver syndrome. prominent. First heart sound is normal, while 2nd heart
2. Acquired sound may be variably split. Depending upon the degree of
• Postoperative: central pulmonary artery hypertension, RV S3 or S4 may
– TOF repair occur.
– Arterial switch operation for transposition of great
vessels Investigation
– Central or Blalock-Taussig shunt
– Pulmonary artery banding
Chest X-ray
May show RA enlargement. MPA may be enlarged if stenosis
is of both branches or diffuse. Decreased vascularity on one
side is characteristic of unilateral obstruction.
2D Echo
May show dilatation of RA/RV and right ventricular
hypertrophy (RVH). The nature and site of stenosis are
demonstrated by echo. One can also estimate RV pressure
from tricuspid regurgitation (TR) Doppler signal.
CT Angiography or MR Angiography
These demonstrate the site and degree of stenosis best. Today,
these are the best guides for intervention.
Perfusion lung scan shows ventilation-perfusion mismatch
362 in affected areas.
Figure 4: Classification of peripheral pulmonary artery stenosis
Indications for Intervention48 across the RVOT and across the lesion. The sheath should be 25
across the lesion by a few mm. Now the stent balloon assembly
1. RV pressure more than 50 percent systemic pressure. is negotiated across the lesion. Once the stent-mounted balloon
http://vip.persianss.ir
5 Echocardiographic diagnosis of congenital heart disease.
Lippincott-Raven; 1999. p. 325.
2. Nadas A. Pulmonary stenosis. In: Flyer DC, Nadae AS (Eds).
Right and Left Ventricular Obstructive Lesions
365
http://vip.persianss.ir
C hapter
Left Ventricular
26 Outflow Tract Obstructions
http://vip.persianss.ir
5 The early diastolic murmur (EDM) may be heard at left sternal
border (LSB) in patients with associated AR. The clinical
features in severe SAS are slow rising, low volume pulse, LV
right and Left VentricuLar oBstructiVe Lesions
diagnosis
Cardiac Catheterization
As SAS is usually associated with other cardiac anomalies both
Figure 6: M-mode shows fluttering of aortic valve and early systolic right and left heart catheterization is recommended. The LV
closure of the aortic valve
is entered with an end hole catheter on a Terumo guide- wire
from aortic end. The pullback tracing is taken from LV apex to
LVOT and then aorta across the AV. However, when subaortic
membrane is very close to AV getting the separate gradient across
the membrane becomes difficult. In patients with associated
VSD there may be little or no gradient across the membrane.
The end-hole catheter is exchanged with pigtail catheter and
LV angiogram is done to demonstrate the SAS (Figure 8). The
aortic root angiogram invariably shows thickened AV without
doming with various degree of aortic regurgitation. The LVH
is obvious in severe SAS. Although percutaneous balloon
dilatation of subaortic membrane was tried in the past this
procedure has not gained popularity because of progressive AR
and progression of SAS itself, despite the good initial results. 21
Figure 7: Subaortic membrane (M) seen just below the aortic valve
in parasternal long-axis view. Color Doppler shows turbulence in the
differential diagnosis 369
left ventricular outflow tract beyond the membrane and in the right
ventricle due to the ventricular septal defect. Ao = Aorta; LA = Left It is important to differentiate valvar, subvalvar and supralvar
atrium; LV = Left ventricle; RV = Right ventricle. stenosis (Table 1).
http://vip.persianss.ir
5 Table 1
Differential diagnosis of valvar, subvalvar and supravalvar aortic stenosis
right and Left VentricuLar oBstructiVe Lesions
Surgery
Surgical resection is the intervention of choice for treatment of
SAS. The excision of membrane is usually done under direct
vision via a transaortic approach using cardiopulmonary
bypass. It is important to resect as much of membrane as
possible without damaging the mitral leaflet or causing
VSD.24 Surgical mortality is low (0-6%) and complications
are generally minimal.17,24 Patients with a resting catheter-
determined or Doppler-derived estimated peak instantaneous
pressure gradient of greater than or equal to 50 mm Hg
have severe SAS and should undergo operative resection of
SAS.25 Surgical intervention should be considered in patients
with lower gradients (peak instantaneous pressure gradient
< 50 mm Hg) if there is LV systolic dysfunction, moderate/
severe AR or a VSD. Development of symptoms attributable
to SAS (angina, dyspnea or syncope/presyncope) with or
immediately after exertion should prompt surgical inter-
vention. Asymptomatic patients planning to become pregnant
Figure 8: Left ventricular (LV) angio in a 8-year-old boy shows severe or wishing to participate in competitive sports should be
subaortic obstruction. LV pressure was 190 mm Hg and pressure considered for SAS resection if the gradient is greater than or
above and below the aortic valve was 114/84 mm Hg (Gradient is 76)
equal to 30 mm Hg.1
Surgical management consists of discrete membrane
excision and/or blunt dissection in focal SAS with focal
Management
septal myomectomy. Tunnel-type SAS is more surgically
Once the Doppler-derived LVOT gradient reaches 50 mm Hg, challenging and often necessitates concomitant myomectomy
there is an increased risk of moderate to severe AR.22 Some or application of the Konno-Rastan procedure to reconstruct
degree of AR occurs in 50 percent of patients with SAS and the LVOT.23,26,27 Concomitant repair of the AV is performed if
moderate or severe AR occurs in 12 percent of patients.23 AR severity is more than mild. SAS recurs in up to 37 percent
The degree of SAS may be underestimated by the pressure of cases after surgical resection.23 In this series, tunnel-type
gradient in the presence of depressed LV function or a non- SAS recurred in 71 percent of patients versus a 14.7 percent
restrictive VSD, that allows left-to-right shunting to the recurrence rate for discrete SAS over 6 years of follow-up.
370 pulmonary arterial circulation. Even discrete SAS was far more likely to recur, however,
if the resting preoperative gradient was greater than 40 mm to get the echocardiography done to detect the SAS in time 26
Hg. The presence of an immediate postoperative gradient of when it can be treated with simple surgical excision and
greater than 10 mm Hg led to progressive recurrent SAS in correction of associated lesions.
http://vip.persianss.ir
5 Williams-Beuren syndrome results from the hemizygous
contiguous gene microdeletion of a region of chromosome
7q11.23 containing 28 genes. It is thought to be caused by
right and Left VentricuLar oBstructiVe Lesions
Pathology
Defective elastin production results in deficient arterial
elasticity causing excessive shear stress and secondary smooth
muscle proliferation and collagen deposition. There is severe
compensatory medial thickening in the large elastic systemic
arteries. The resultant obstruction to the lumen of the vessels
ranges from localized stenosis of the proximal ascending aorta
to diffuse narrowing extending into the arch and may affect the
entire aorta, renal arteries and other major aortic branches.44-46 Figure 9: Transthoracic echocardiography in parasternal long axis
shows diffuse narrowing of aorta (type II). Ao = Aorta; LA = Left atrium;
The origins of the coronary arteries may be involved. Other LV = Left ventricle.
large elastic arteries like pulmonary arteries may also be
involved.44 The edge of the obstructing tissue may impinge
on a sinus of Valsalva, compromising flow to the coronary are present in 7 percent.44 The origin of the coronary arteries
ostia. Occasionally, the coronary occlusion is complete, a is usually proximal to the obstruction and they are subjected
leaflet of the distorted AV adhering to the obstructing collar to high systolic pressure and limited diastolic flow. There
of tissue. When the aortic lumen is compromised, there is may be partial or complete ostial obstruction of the coronary
proportionate left ventricular hypertension and hypertrophy. arteries, ectasia or aneurysm of the coronary arteries. Proximal
The obstruction is commonly localized, but in about 20 coronary artery involvement may be caused either by coronary
percent, it extends diffusely into the ascending aorta (Figure artery medial hypertrophy or by adherence of aortic cusps to
9). The aortic cusps are often thickened and distorted, the ostial walls. Coronary artery involvement is a cause for
sometimes adherent to the aortic wall, but although AR is increased risk of sudden cardiac death in these children as
common, it is rarely severe. Williams-Beuren syndrome is a compared to the normal population.44
neurodevelopmental disorder with characteristic facies, SVAS
and mental retardation. Children with this condition have Clinical Features
distinctive elfin facial features, a hoarse voice associated with
growth retardation, mental retardation and an overfriendly Most children with SVAS are asymptomatic at the time of
personality; hyperacusis, infantile hypercalcemia and pre- diagnosis.44 Patients with significant LVOTO may present
maturely wrinkled skin are other associated features.40 with angina, dyspnea or syncope. On examination, children
may have dysmorphic features. The right radial, brachial
Classification pulses are better felt than the left as the jet of blood flow
from the SVAS has a preferential trajectory into the right
The SVAS is classified as three morphologic subtypes as brachiocephalic (innominate) artery. This is called the
shown in Figures 10A to C:7,45,46 ‘Coanda effect’ in which the blood pressure is more in the
1. Hourglass type/deformity (50–75%). right upper limb than in the left upper limb (the difference
2. Diffuse type (25%). being > 10 mm Hg). The rest of the clinical findings are that
3. Rarely there may be a third subtype, a discrete membrane of LVOTO similar to aortic valvar stenosis except for the
above the valve. This may be a localized variety of the absence of an aortic valve click.
hourglass deformity.
diagnosis
Associations
Electrocardiogram
The commonest associated anomaly is hypoplasia of the
372 right ventricular outflow tract and branch pulmonary arteries, Electrocardiogram may show LVH with or without ST
which is reported in 64 percent. Coronary artery abnormalities changes.
26
Figures 10A to C: A. Hourglass type; B. Diffuse narrowing of ascending aorta; C. Discrete membrane above the aortic valve
Chest X-ray
On chest X-ray the only finding that may suggest the diagnosis
of SVAS is the absence of poststenotic dilatation of the aorta.47
Echocardiography
Supravalvar aortic stenosis was first identified by cardiac
catheterization and later echocardiography (Figures 11A and
B) has been shown to have good correlation with the ratios
calculated from angiography. Good correlation was also
shown between the ratio of the surface areas calculated from
the echocardiogram and the corresponding measured pressure a
differences.48,49 Echocardiographically and angiographically
it is diagnosed as congenital stenosis of the ascending aorta
distal to the aortic annulus.44 The characteristic finding is the
narrowing of the diameter of the aortic lumen at the stenotic
area just distal to the AV. As the transducer sweeps further
cephalad, the aortic lumen widens to a normal diameter.50
It has been shown that TEE images are far superior to TTE
and TEE can define the mechanism of coronary artery ostial
obstruction associated with SVAS.51 In adults, TTE and TEE
are done to demonstrate the diameter and anatomy of the aortic
sinus, sinotubular ridge and the proximal ascending aorta.
Also origins of the coronary arteries, the systolic gradient
across the SVAS and the degree of LVH can be demonstrated.
Catheterization
B
As there may be long-segment obstruction, assessment of
Figures 11A and B: A. Transthoracic echocardiography in apical five
the gradient may require cardiac catheterization for complete chamber view shows type III discrete membrane causing SVAS in a 6
assessment of hemodynamic severity of the stenosis. The year old boy; B. CW Doppler shows 107 gradient. AV = Aortic valve;
373
morphology of the stenotic lesion may be classified as either LV = Left ventricle; SVAS = Supravalvar aortic stenosis
http://vip.persianss.ir
5 loacalized (Figure 12) or diffuse. The localized phenotype is been seen to gradually improve with time. Therefore, most
limited to the sinotubular junction and proximal ascending of the children with SVAS are managed expectantly and a
aorta. This is described as the hourglass appearance large proportion of the children managed non-surgically,
right and Left VentricuLar oBstructiVe Lesions
angiographically. In the diffuse phenotype, changes are demonstrate stable peak LVOT gradients and gradual
not limited to the supravalvar region and luminal hypoplasia improvement in ascending aortic dimensions. The overall
may extend into the distal ascending aorta, arch or beyond. mortality in SVAS is low.44 Operation has been recommended
The transverse arch, coarctation shelf and descending thoracic for patients with SVAS of either the discrete or diffuse types
aorta may also display areas of narrowing. According to with symptoms such as angina, dyspnea or syncope and for
various studies about 18 to 30 percent are of the diffuse type. patients with mean gradient greater than 50 mm Hg or peak
A smaller indexed transverse aortic arch diameter has been instantaneous gradient by Doppler echocardiography greater
shown to be associated with Williams-Beuren syndrome.44 than 70 mm Hg. Surgical repair may also be recommended
for adults with lesser degrees of supravalvar LVOTO when
Computed Tomography/Magnetic Resonance Imaging associated with symptoms or LVH or LV systolic dysfunction
or if pregnancy is planned.54
The ECG-gated multidetector computed tomography (CT)
and magnetic resonance imaging (MRI) are also useful in the Summary—Supravalvar Aortic Stenosis
diagnosis of SVAS owing to their high sensitivity in diagnosing
anomalies of the mediastinal vessels.52,53 It is recommended The severity of SVAS is variable and it often requires surgical
that MRI or CT can be performed in adult patients to assess intervention. A lack of treatment may result in progressive
the anatomy of the LVOT, the ascending aorta, coronary artery heart failure and can be fatal.
anatomy and flow. Also one can assess the main and main and
branch pulmonary artery anatomy and flow.
SHONE’S ANOMALY
Management Multiple levels of left heart obstruction are found in patients
with Shone’s anomaly, which was first described in 1963 by
A large proportion of children with congenital SVAS may Shone et al.10 In their abstract they described this anomaly
not need surgical intervention because the lesion gradually as follows–“A developmental complex is described in which
regresses overtime. The indexed LVOT dimensions have four obstructive anomalies of the left side of the heart and
been observed to increase overtime in patients who did not aorta coexist.” These anomalies are:
undergo an operation. The natural history of pulmonary 1. Parachute mitral valve
arterial involvement in Williams-Beuren syndrome has also 2. Supravalvar ring of left atrium
3. Subaortic stenosis of either the muscular or membranous
type
4. Coarctation of the aorta.
Eight cases form the basis of this report. In two cases, each
of the four anomalies was present; all of the other six cases
represent partial forms of the complex or formes frustes, in that
only two or three of the anomalies were present. The clinical
picture is compounded due to the effects of several anomalies
of the complex and of the frequent association with still other
anomalies, including VSD. In practice, in Shone’s anomaly,
the lesions of valvar mitral, AS and SVAS have been included.
In patients with Shone’s anomaly, a wide spectrum of severity
exists in each of the obstructive components. This creates a
non-uniform group of patients with varied presentations and
long-term outcomes. 55
Clinical Features
The clinical presentation of patients with Shone’s anomaly
depends on the dominant level of obstruction to flow within
the left heart. With obstruction at the level of the mitral
Figure 12: Aortic root angiogram shows type I hourglass supravalvar valve secondary to a supravalvar mitral ring (Figure 13)
374 stenosis (arrows) with both right and left coronaries arising from single
or a parachute mitral valve as the dominant lesion, these
left coronary ostia
Brauner et al56 described the presentation of 19 consecutive 26
patients with Shone’s anomaly. Two patients presented with
asymptomatic murmurs; the remaining presented with varying
Investigations
In the past, the complete diagnosis of Shone’s complex
diagnosis was done by autopsy but today the modern tool
like two-dimensional transthoracic echocardiography and
Figure 13: Transthoracic echocardiography in modified two chamber
view shows supramitral ring (SMR with arrow) with deformed parachute
Doppler evaluation is excellent for assessing the severity
mitral valve. LA = Left atrium; LV = Left ventricle. of various lesions. One of our patients, a 12 years old girl
of Shone’s complex had parachute mitral valve (Figures
14A and B), interruption of aorta diagnosed on TTE and
patients present with congestive heart failure (CHF), with confirmed on CT angio (Figures 15A and B). She also had
an enlarged left atrium and passive pulmonary congestion bicuspid aortic valve (Figure 16). Cardiac catheterization is
noted on chest X-ray. These patients are at risk for pulmonary performed to further evaluate the pressure gradients across
artery hypertension (PAH) and may have palpable pulmonary the LVOT (i.e. subvalvar, valvar, supravalvar and COA) and
component of the second heart sound (P2). When the dominant to obtain the pulmonary artery pressure, noting the presence
lesion is at the level of the aortic valve (i.e. subvalvar, or and severity of PAH. The angiogram is done to delineate the
supravalvar), these patients present with heaving apical various obstructions (Figures 17A to D). Serial evaluations
impulse due to LVH and a harsh ejection systolic murmur. are required because the obstructive nature of the lesions is
LVH with strain pattern is possibly seen on ECG. If the usually progressive.
dominant lesion is coarctation of the aorta, the patient may Of the patients in the study by Brauner et al,56 the anatomic
present with hypertension in upper limbs and decreased lesions found were as follows: mitral valve abnormalities
pressure in lower limbs with radiofemoral delay in pulse. Age in 100 percent (supravalvar mitral ring 47%, parachute
of presentation may vary from the newborn period in severely mitral valve 63%), SAS in 79 percent (discrete membrane
affected infants to early school age in less-affected children. 67%, long segment fibromuscular tunnel 33%), BAV in
a B
Figures 14A and B: A. Transthoracic echocardiography in a in 12-year-old girl shows parachute mitral valve (PMV) with single papillary muscle 375
(SPM) in apical 2 chamber view; B. Parasternal short axis view at papillary muscle level. LA = Left atrium; LV = Left ventricle.
http://vip.persianss.ir
5
right and Left VentricuLar oBstructiVe Lesions
Management
The management of patients with Shone’s anomaly depends
on the age of the patient and the dominant lesion. Neonates
who present with severe coarctation of the aorta are started on
prostaglandin (PGE1) and the metabolic acidosis corrected.
They are treated either by percutaneous balloon aortoplasty
or surgical repair of the COA is performed. If these neonates
present with the dominant lesion of critical aortic stenosis,
they are started on PGE1 metabolic acidosis corrected and AS
is treated either by percutaneous balloon valvuloplasty or by
surgical valvotomy. The transcatheter balloon valvuloplasty
and balloon aortoplasty is done as a safe bridge to future
intracardiac repair. In neonates with the dominant lesion of
left ventricular inflow obstruction (i.e. mitral stenosis and
Figure 16: Parasternal short axis in the same patient with Shone's supravalvar mitral ring), the resultant CHF is treated medically
376 complex shows bicuspid aortic valve until surgical resection of the supravalvar mitral ring, mitral
26
valvuloplasty or mitral replacement is performed. When the years. Of the 14 survivors, 10 had significant hemodynamic
dominant lesion is LVOTO then surgical resection of the SAS abnormalities, including AS, left ventricular dysfunction,
with or without ventricular septal myomectomy, aortic valve mitral stenosis or regurgitation, pulmonary hypertension, or
repair or left ventricle to ascending aorta homograft placement recoarctation of the aorta.
is performed.55 The median age at first operation in the 19
patients described by Brauner et al was 4.2 months (range, 2 Summary—Shone's Anomaly
day–4.5 year). Specifically, the median age at intervention for
coarctation of the aorta was 1.5 months (2 day–2 year); for LV Patients with Shone’s anomaly require lifelong follow-up
inflow obstruction, the median age was 2.1 years (1 month–7 even after transcatheter procedure or surgical correction,
year); and for LVOT obstruction, the median age was 2.5 ± because the obstruction at various levels may progress or
1.5 years. These 19 patients underwent 46 major operations, recur. Several procedures are usually required, either by
including 94 distinct surgical procedures.56 surgery or by interventional cardiac catheterization, to repair
or palliate the obstructive lesion. The treatment of these
Prognosis patients continues to evolve and, despite the complexity of
these patient's lesions, the morbidity and mortality rates have
The surgical outcomes of patients with Shone’s anomaly as decreased and are expected to decrease further in the future.
noted by Brauner et al56 seemed to vary with the age at initial
intracardiac repair, severity of PAH and severity of the mitral Formerly, when religion was strong and science weak, men
valve lesion. The operative mortality rate was as high as 16 mistook magic for medicine; now, when science is strong 377
percent, the total mortality rate was 26 percent. The actuarial and religion weak, men mistake medicine for magic.
survival rate was 79 percent at 1 year and 73 percent at 7 —Thomas Szasz, The Second Sin, 1973
http://vip.persianss.ir
5 REFERENCES 21. Suárez de Lezo J, Pan M, Sancho M, et al. Percutaneous
transluminal balloon dilatation for discrete subaortic stenosis.
1. Aboulhosn J, Child JS. Left ventricular outflow obstruction: Am J Cardiol. 1986;58:619-21.
right and Left VentricuLar oBstructiVe Lesions
subaortic stenosis, bicuspid aortic valve, supravalvar aortic 22. McMahon CJ, Gauvreau K, Edwards JC, et al. Risk factors for
stenosis, and coarctation of the aorta. Circulation. 2006;114: aortic valve dysfunction in children with discrete subvalvar
2412-22. aortic stenosis. Am J Cardiol. 2004;94:459-64.
2. Fedderly RT. Left ventricular outflow obstruction. Pediatr Clin 23. Brauner R, Laks H, Drinkwater D, et al. Benefits of early
North Am. 1999;46:369-84. surgical repair in fixed subaortic stenosis. J Am Coll Cardiol.
3. Armstrong WF, Ryan T (Eds). Feigenbaum’s Echocardiography. 1997;30:1835-42.
Lippincott Williams and Wilkins; Philadelphia. 2009. 24. Chaikhouni A, Crawford FA Jr, Sade RM, et al. Discrete
4. Cheevers N. Observations on the diseases of the orifice and subaortic stenosis. Clin Cardiol. 1984;7:289-93.
valves of the aorta. Guys Hosp Rep. 1842. pp. 387-442. 25. Gersony WM. Natural history of discrete subvalvar aortic
5. Rosenquist GC, Clark EB, McAllister HA, et al. Increased stenosis: management implications. J Am Coll Cardiol.
mitral aortic separation in discrete subaortic stenosis. 2001;38:843-5.
Circulation. 1979;60:70-4. 26. Konno S, Imai Y, Lida Y, et al. A new method for prosthetic
6. Campbell M. Natural history of congenital aortic stenosis. Br valve replacement in congenital aortic stenosis associated with
Heart J. 1968;30:514-26. hypoplasia of the aortic valve ring. J Thorac Cardiovasc Surg.
7. Latson LA. Aortic stenosis: Valvular supravalvular, and fibromus- 1975;70:909-17.
cular subvalvular. In: Garson A Jr, Bricker JT, Fisher DJ, Neish 27. Rastan H, Koncz J. Aortoventriculoplasty: a new technique
SR (Eds). The Science and Practice of Pediatric Cardiology. 2nd for the treatment of left ventricular outflow tract obstruction. J
edition. USA: Williams and Wilkins; 1998. pp. 1257-76. Thorac Cardiovasc Surg. 1976;71:920-7.
8. Cilliers AM, Gewillig M. Rheology of discrete subaortic 28. Coleman DM, Smallhorn JF, McGrindle BW, et al.
stenosis. Heart. 2002;88:335-6. Postoperative follow-up of fibromuscular subaortic stenosis. J
9. Urbach J, Glaser J, Balkin J, et al. Familial membranous Am Coll Cardiol. 1994;24:1558-64.
subaortic stenosis. Cardiology. 1985;72:214-7. 29. Rizzoli G, Tiso E, Mazzucco A, et al. Discrete subaortic stenosis:
10. Shone JD, Sellers RD, Anderson RC, et al. The developmental operative age and gradient as predictors of late aortic valve
complex of “parachute mitral valve,” supravalvular ring of incompetence. J Thorac Cardiovasc Surg. 1993;106:95-104.
left atrium, subaortic stenosis, and coarctation of aorta. Am J 30. Douville EC, Sade RM, Crawford FA Jr, et al. Subvalvar aortic
Cardiol. 1963;11:714-25. stenosis: timing of operation. Ann Thorac Surg. 1990;50:29-34.
11. Roberts WC. Valvular, subvalvular and supravalvular aortic 31. Firpo C, Maitre Azcarate MJ, Quero Jimenez M, et al. Discrete
stenosis: morphologic features. Cardiovasc Clin. 1973;5:97-126. subaortic stenosis in childhood: a congenital or acquired disease?
12. Wright GB, Keane JF, Nadas AS, et al. Fixed subaortic stenosis Follow up in 65 patients. Eur Heart J. 1990;11:1033-40.
in the young: medical and surgical course in 83 patients. Am J 32. de Vries AG, Hess J, Witsenburg M, et al. Management of fixed
Cardiol. 1983;52:830-5.
subaortic stenosis: a retrospective study of 57 cases. J Am Coll
13. Katz NM, Buckley MJ, Liberthson RR. Discrete membranous
Cardiol. 1992;19:1013-7.
subaortic stenosis: report of 31 patients, review of the literature,
33. Jacobs JP, Palatianos GM, Cintron JR, et al. Transaortic
and delineation of management. Circulation. 1977;56:1034-8.
resection of the subaortic membrane: treatment for subvalvular
14. Rayburn ST, Netherland DE, Heath BJ. Discrete membranous
aortic stenosis. Chest. 1994;106:46-51.
subaortic stenosis: Improved results after resection and
34. Rao PS, Wilson AD, Chopra PS. Balloon dilatation for discrete
myectomy. Ann Thorac Surg. 1997;64:105-9.
subaortic stenosis: immediate and intermediate-term results. J
15. Perloff JK, Marelli AJ. Congenital Aortic stenosis; Congenital
Invasive Cardiol. 1990;2:65-70.
Aortic regurgitation. In: Perloff JK, Marelli AJ (Eds). Perloff's
clinical Recognition of Congenital Heart Diseases, 6th edition. 35. Freedom RM, Pelech A, Brand A, et al. The progressive nature
Philadelphia: Saunders; 2010. pp. 74-100. of subaortic stenosis in congenital heart disease. Int J Cardiol.
16. Schneeweiss A, Motro M, Shem-Tov A, et al. Discrete subaortic 1985;8:137-48.
stenosis associated with congenital valvular aortic stenosis:a 36. Williams JCP, Barratt-Boyes BG, Lowe JB. Supravalvular
diagnostic challenge. Am Heart J. 1983;106:55-9. aortic stenosis. Circulation. 1961;24:1311-8.
17. Newfeld EA, Muster AJ, Paul MH, et al. Discrete subvalvular 37. Denie JJ, Verheugt AP. Supravalvular aortic stenosis.
aortic stenosis in childhood. Study of 51 patients. Am J Cardiol. Circulation. 1958;18:902-8.
1976;38:53-61. 38. Beuren AJ, Schulze C, Eberle P, et al. The syndrome of
18. Kelly DT, Wulfsberg E, Rowe RD. Discrete subaortic stenosis. supravalvular aortic stenosis, peripheral pulmonary stenosis,
Circulation. 1972;46:309-22. mental retardation and similar facial appearance. Am J Cardiol.
19. Reis RL, Peterson LM, Mason DT, et al. Congenital fixed 1964;13:471-83.
subvalvular aortic stenosis. An anatomical classification and 39. Kitchiner D, Jackson M, Malaiya N, et al. Incidence and prognosis
correlations with operative results. Circulation. 1971;43(5 of obstruction of the left ventricular outflow tract in Liverpool
suppl):111-8. (1960-91): a study of 313 patients. Br Heart J. 1994;71:588-95.
20. Kleinert S, Geva T. Echocardiographic morphometry and 40. Dutra RL, Pieri Pde C, Teixeira AC, et al. Detection of deletions
geometry of the left ventricular outflow tract in fixed subaortic at 7q11.23 in Williams-Beuren syndrome by polymorphic
stenosis. J Am Coll Cardiol. 1993;22:1501-8. markers. Clinics (Sao Paulo). 2011;66:959-64.
378
41. Martin EC, Moseley IF. Supravalvar aortic stenosis. Br Heart
J. 1973;35:758-65.
49. Weyman AE, Caldwell RL, Hurwitz RA, et al. Cross-sectional
echocardiographic characterization of aortic obstruction.
26
42. Keane JF, Fyler DC. Aortic outflow abnormalities. In: Keane 1. Supravalvular aortic stenosis and aortic hypoplasia.
379
http://vip.persianss.ir
C hapter
Left ventricular inflow obstructions are an extremely rare form a. Congenital mitral stenosis
of congenital heart disease (CHD). It includes a number of Parachute mitral valve
malformations, either single or in combination, that orginate Anomalous mitral arcade
proximal or at the mitral valve. These malformations are Double orifice mitral valve
acyanotic heart diseases with no shunt lesion, but they can Accessory mitral valve tissue/orifice
cause pulmonary venous and pulmonary arterial hypertension, b. Hypoplastic mitral valve.
with very similar clinical manifestations. Although their
existence in isolation is described, most of the left ventricular OBSTRUCTIONS ABOVE THE MITRAL VALVE
inflow anomalies exist in conjunction with anomalies of left
sided structures. The anomalies can be described as per the
Cor Triatriatum Sinister
anatomical site at the supramital , mitral valve annulus, mitral
leaflets and submitral apparatus levels. Cor triatriatum is a heart with three atria (triatrial heart). It is
They left ventricular inflow obstructions are broadly rare and has been reported in 0.1–0.5% of all congenital heart
divided into: diseases. In Cor triatriatum sinister (also known as divided
1. Obstruction above the mitral valve left atrium) a partition divides the left atrium into a proximal
a. Cor triatriatum portion (the pulmonary sinus), into which the pulmonary
b. Supravalvular stenosing ring veins drain and a distal portion (the left atrium) that empties
c. Pulmonary vein stenosis into the left ventricle through the mitral valve and to which
d. Hypoplastic pulmonary veins the appendage is attached (Figures 1A to C). Cor triatriatum
2. Obstruction at the level of the mitral valve dexter is the persistence of right valve of the sinus venosus.
A B C
Figures 1A to C: A. Schematic image of Cor triatriatum; B. Apical four chamber zoomed up view on two-dimensional echocardiography showing
shelf in left atrium, stretching from atrial septum on right side to left atrium lateral wall on left side; C. Zoomed up view of the left atrium with color
flow mapping showing turbulence (mosaic jet) starting in mid atrial cavity. DC = Distal chamber; LV = Left ventricle; PC = Proximal chamber; RA
= Right atrium; RV = Right ventricle.
Pathological Anatomy Box 1: Anatomic classification of Cor triatriatum
27
(incidence of each lesion is mentioned in the brackets)
The partition in left atrium was first recognized by Andral in
http://vip.persianss.ir
5
right and left ventricular obstructive lesions
A B C D
E F G H
Figures 2A to H: Variants of Cor triatriatum: A. Classic Cor triatriatum. The pulmonary venous chamber (PVC) receives the right and left
pulmonary veins (RPV and LPV respectively) and the only egress for pulmonary venous return is through the opening in the Cor triatriatum
(arrow); B. Cor triatriatum with a communication between the PVC and the right atrium (RA). This communication allows decompression of
the PVC; C. Cor triatriatum with an anomalous connection between the PVC and the left innominate vein (LIV). This anomalous connection
(levoatriocardinal vein) decompresses the PVC. The PVC does not communicate directly with the left atrium (LA); D. Pulmonary venous
return reaches the right atrium through a communication between the PVC and the right atrium. Blood then reaches the LA via the foramen
ovale; E. The PVC decompresses via a vertical vein to the portal vein. Subtotal Cor triatriatum; F. The confluence of the RPV communicates
with the LA via a stenotic orifice. The LPV connect normally to the LA; G. Subtotal Cor triatriatum of the right pulmonary veins associated
with partially anomalous pulmonary venous connection of the veins LPV to the LIV; H. Subtotal Cor triatriatum of the RPVs to the RA via a
stenotic orifice. The (LPV) connect normally. IVC = Inferior vena cava; LV = Left ventricle; RV = Right ventricle; SVC = Superior vena cava;
VV = Vertical vein. (Adapted from: Krabill KA, Lucas RV Jr. Abnormal pulmonary venous connections. In: Emmanouilides GC, Reimenschneider
TA, Allen HD, et al, (Eds). Heart Disease in Infants, Children, and Adolescents. 5th edition Baltimore: Williams and Wilkins, 1995;839-874).
the mitral valve during systole, reflecting the reversal of a persistent left superior vena cava, often associated with an
gradient as the left ventricular contraction exerts pressure on unroofed coronary sinus. Other abnormalities of the left atrium
the membrane through the closed mitral valve. or mitral valve can also occur, possibly more frequently than
Associations: As is evident with the hemodynamics of can be accounted for by coincidence. Mitral regurgitation often
the lesion, about two-thirds of the patients have associated occurs and can be severe and a supramitral stenosing ring has
congenital cardiac lesions. Atrial septal defect, either a patent been seen. Apart from these atrial and venous anomalies, there
foramen ovale or a true fossa ovalis defect, occurs in about are occasional associations with most other forms of congenital
half of the patients. If the defect connects the right atrium to heart disease: patent ductus arteriosus, ventricular septal defect
the true left atrium (lower chamber), then it is not a part of (VSD), coarctation of the aorta, pulmonary stenosis, valvar
the classification. A sinus venosus defect has been reported. aortic stenosis (including bicuspid aortic valve) or subvalvar
Atrioventricular septal defects are quite common, ranging aortic stenosis, tetralogy of Fallot, Ebstein anomaly, double-
from ostium primum defects (often intermediate) to a common outlet right ventricle, hypoplastic left heart syndrome and
atrium and less frequently, a complete atrioventricular canal. occasionally other anomalies. Abnormalities of situs and
Abnormalities of the pulmonary veins (partial or total heterotaxies are uncommon. The right-sided chambers are
382 anomalous pulmonary venous connection) are common, as is hypertrophied if there is significant pulmonary hypertension.
Coronary Sinus Obstruction leaflet and may or may not be obstructive (Figures 3A and 27
B). The tissue may form an obstructing fibrous ring or shelf
Persistent left superior vena cava may lead to coronary sinus involving the atrial wall and extending to the leaflet. The tissue
A B
C D
383
Figures 3A to D: A. Apical four chamber view with color flow mapping in a case of supramitral ring causing left ventricular inflow obstruction; B.
Turbulent flow starts above the level of mitral annulus; C and D. Apical four chamber view with color flow mapping in a case of annular type of
supramitral ring causing left ventricular inflow obstruction. Turbulent flow starts at the level of mitral annulus. LA = Left atrium; LV = Left ventricle;
RA = Right atrium; RV = Right ventricle.
http://vip.persianss.ir
5 severe. One should maintain a high index of suspicion for
this condition in patients with signs and symptoms of left-
sided heart obstruction, particularly in the face of other mitral
right and left ventricular obstructive lesions
investigations
Electrocardiogram: Broad notched left atrial P waves have Figure 4: The various components of the mitral valve with chordae
been ascribed to the prolonged conduction in the proximal tendinae and two papillary muscles. AML = Anterior mitral leaflet;
PML = Posterior mitral leaflet
accessory chamber. Rest of the electocardiogram (ECG)
finding are essentially similar to that of mitral stenosis as
described later in the chapter.
X-ray: The radiological appearance of pulmonary venous
congestion without left atrial enlargement is a radiological
feature of Cor triatriatum. Rest of the features of pulmonary
congestion and pulmonary hypertension as seen in mitral
stenosis may be observed.
Anatomy
Mitral valve consists of the annulus, two leaflets, two
papillary muscles and two sets of chordae tendineae (Figure
4). The atrioventricular orifice is reinforced by the annulus
fibrosis of the cardiac skeleton in the posterior and lateral
two thirds of the annulus. The remaining medial third is Figure 5: The mitral valve orientation within the heart and its resemb-
supported by attachment to the left atrium and by fibrous elance to the cardinal’s hat “mitre” and hence the name mitral valve
support to the aortic semilunar valve. The bicuspid mitral
valve has two leaflets—anterior (medial or aortic) and
posterior (inferior or mural, ‘wall’) resembling the cardinal’s
hat or mitre, hence the term mitral valve (Figure 5). The even when the atrium is contracting and the ventricle is filling.
anterior leaflet is trapezoidal shaped and its attachment on The junctions of the two leaflets are called anterolateral and
the annulus to its free edge is longer (twice that of posterior the posteromedial commissures. The line of apposition of
leaflet) than the length of attachment across the annulus. the leaflets during valvular closure is indicated by a fibrous
The posterior leaflet is relatively narrow, with a very long ridge. There are two papillary muscles that extend from the
attachment distance across the annulus with its free edge ventricular free wall. The anterior papillary muscle is slightly
subdivided into the anterior, central and posterior crescent larger than the posterior and each papillary muscle consists
shapes (Figures 6). of a major trunk that often has multiple chordae tendineae.
Papillary muscles in conjunction with chordae tendineae, The chordae tendineae of each papillary muscle extends to
attach to the leaflets in order to secure them in place to the two valvular commissures and to the multiple crescent
prevent the prolapse of the leaflets up into the atrium. There shapes of the posterior cusp. In addition, the posterior leaflet
is considerable overlap of the leaflets, when the valves are in occasionally has chordae that extend from the ventricular
384 the closed position and they remain relatively close together myocardium without a papillary muscle.
the free edges of the dysplastic valve leaflets are thickened 27
and rolled, the valve may be incompetent as well as stenotic.
A B
Figures 7A and B: A. Two-dimensional echocardiography from apical four-chamber view showing hypoplastic mitral valve annulus (arrows),
hypoplastic left ventricle cavity with dilated right ventricle; B. Echocardiography of a neonate with hypoplastic left heart syndrome apical four- 385
chamber view showing dilated right ventricle and hypoplastic left ventricle. la = Left atrium; LV = Left ventricle; ra = Right atrium; RV = Right
ventricle
http://vip.persianss.ir
5 leaflets, dividing the valvular orifice into two components,
with each orifice then supported by one of the papillary
muscles. Isolated DOMV is unusual and may be an incidental
right and left ventricular obstructive lesions
Ebstein Malformation of the Mitral Valve A rarer abnormality that can result in congenital mitral valvar
regurgitation is hypoplasia of the mural leaflet, such that the
Ebstein malformation can rarely affect the morphological valve leaflets cannot coapt normally during systole.
mitral valve. When this is the case, the mural leaflet is plas-
tered down onto the ventricular wall, with its hinge below the Overriding of Valvar Leaflets
atrioventricular junction. In this setting, there is no thinning
of the atrialized inlet portion, as is usually seen when it is More frequent is straddling and overriding of the valvar leaflets.
the morphological tricuspid valve that is deformed in the set- These anomalies can affect either the tricuspid or the mitral
ting of concordant atrioventricular connections. Such lack of valve. Bridging of leaflets is also a common feature of the
morphologic atrialization is also a feature of Ebstein common atrioventricular valve, albeit that a common valve can
malformation of the left-sided atrioventricular valve in the set- be exclusively connected to one or other of the ventricles. It
ting of congenitally corrected transposition (Ebsteinoid valve). is the spectrum between the commitment of straddling valves
to one or other ventricle, underscoring the difference between
Funnel-Shaped Valve functionally univentricular and biventricular arrangements.
When the morphological mitral valve straddles and overrides,
Another isolated anomaly of the valvular leaflets is the so called the valve always straddles through an anterosuperior inter
funnel-shaped valve. This entity is characterized by thickening ventricular communication and is found with either discordant
and retraction of the leaflets, with fused tendinous cords, but in or double outlet ventriculoarterial connections.
the presence of normal papillary muscles. The funnel produces
mitral stenosis. It is rare in postmortem collections. Fibrous Ridge that Anchors Together the
Aortic and Mural Components
Dual Orifices of Mitral Valve
While discussing malformations of the leaflets, we should
Dual orifices of mitral valve (DOMV) are produced by a tongue also pay attention to a fibrous ridge that anchors together the
386 of valvular tissue that extends between the mural and aortic aortic and mural components, narrowing the valvular orifice.
27
Although usually described as a supravalvular structure, the one can see either direct insertion of the leaflets into the
abnormal fibrous shelf is an integral part of the atrial surface papillary muscles or insertion through short, thick chordae.
of the leaflets and can readily be removed at surgery. Shelves Also seen is the bridge of fibrous tissue adherant to the
can exist within the left atrium and produce true supravalvular inferior aspect of anterior mitral leaflet (Figure 10). This
rings, but these are much rarer than the variant attached to the abnormality usually results in both mitral stenosis and mitral
atrial aspect of the leaflets. regurgitation. Abnormal mitral arcade may be association
with atrial septal defect, patent ductus arteriosus, valvular
Mitral Valve Prolapse and subvalvular aortic stenosis and coarctation of aorta.
The commonest lesion afflicting the leaflets of the mitral valve is Anomalies of the Papillary Muscles
prolapse. The problems concerning the pathology of prolapse of
the mitral valve, however, are as numerous as those concerning
Parachute Mitral Valve
its clinical features. There is no unanimity concerning
nomenclature or etiology and perhaps more important, no Parachute mitral valve is characterized by unbalanced chordal
standard definition of what precisely constitutes prolapse of the attachments to a single papillary muscle. Two variants include:
leaflets. More commonly the lesion is associated with mitral
regurgitation than mitral stenosis and hence being discussed in
in the chapter on mitral valve diseases (Chapter 31).
http://vip.persianss.ir
5 1. Two papillary muscles, but focalized chordal attachments muscles and milder than those with supravalvular mitral
(commoner). ring.
2. A classic type with a single papillary muscle (Figures 11A Commonly associated conditions include isolated or
right and left ventricular obstructive lesions
Figures 11 A and B: A. Transthoracic echocardiography (TTE) zoomed up echocardiographic image illustrates chordal attachment to a single
388 papillary muscle in a 12-year-old case of parachute mitral valve; B. TTE in short axis shows mitral valve orifice with single papillary muscle
(SPM). Image Courtesy: Dr IB Vijayalakshmi
variable degrees of subaortic obstruction and also because In children with mitral stenosis, isolated pulmonary venous 27
of anomalous mitral valve leaflet or chordal attachments to obstruction is associated with arterial and pulmonary venous
the left ventricular septum. Associated forms of congenital medial muscular hypertrophy, as early as 12 months of age.
http://vip.persianss.ir
5 obstruction. The rise in pulmonary vascular resistance and presence and type of associated lesions and the growth rate
consequent fall in pulmonary blood flow, means that, on of the infant. Mitral inflow obstructive lesions are generally
sequential cardiac catheterizations in individuals with mitral symptomatic in fetal and early neonatal life. Infants with less
right and left ventricular obstructive lesions
stenosis, the gradient is frequently found to fall. severe mitral valve obstruction or less significant associated
Although the natural history of pulmonary hypertension lesions, generally present beyond the neonatal period with
in children with acquired mitral valve stenosis suggests that a history of antecedent pulmonary infections and failure to
pulmonary hypertension, generally resolves postoperatively, gain weight appropriately. Other features include irritability,
this is not necessarily the case with longer-standing congenital exhaustion at feeding, diaphoresis, tachypnea and chronic
mitral valvular disease and severe or chronic pulmonary cough. Congenital mitral stenosis is associated with syncope,
hypertension. Consequently, the substrate for pulmonary but seldom with hemoptysis. Aphonia may occur because of
hypertension remains a significant acute postoperative risk compression of recurrent laryngeal nerve by hypertensive
factor and underscores the importance of pulmonary vasodilator pulmonary trunk. Clinical features associated with a
management in the initial postoperative period. In patients particularly poor outcome are presentation early in infancy,
with severe mitral stenosis, the reduction of left ventricular signs of low systemic cardiac output and right-sided heart
volume or mass, ischemia, fibrosis and left ventricular failure. On examination severe mitral valve obstruction is
dysfunction may also compromise cardiac output. Critical associated with diminished peripheral perfusion and pulses.
reduction of cardiac output and vital organ dysfunction leads Normal sinus rhythum is generally a rule in congenital
to metabolic insufficiency and cachexia. Chronic low cardiac mitral stenosis. Jugular venous pulse shows increased ‘a’
output is associated with peripheral circulatory maladaptation wave secondary to pulmonary hypertension. Palpation of the
including excessive stimulation of the sympathoadrenal axis heart will reveal either a normal impulse or right ventricular
and systemic vasoconstriction. hypertrophy and there may be an apical diastolic thrill.
Finally, renal insufficiency, fluid and electrolyte imbalance Pulmonary valvar closure will be palpable if pulmonary
are caused by abnormal intake, renal hypoperfusion and hypertension is severe. The first heart sound in contrast to
hormonal factors. While associated distal obstructive lesions acquired rheumatic mitral stenosis, is relatively soft and mitral
may exaggerate the mitral insufficieny, by contrast, severe valve opening sound (snap) is usually absent, because the
pulmonary stenosis in the setting of a VSD may mask entirely mitral valve leaflets are relatively inflexible and immobile. The
the effects of the valvar obstruction by reducing the flow of second heart sound varies from widely split to narrowly split
blood to the lungs. Left atrial pressure is bound to be lower than with an accentuated pulmonary component, when pulmonary
pulmonary arterial pressure, irrespective of the severity of the hypertension is present. Although, left ventricular inflow tract
mitral obstruction and hence the hemodynamic data observed. obstruction should preclude auscultation of ventricular filling
sounds, right ventricular third or fourth heart sounds may be
INCIDENCE AND ETIOLOGY present. A low-frequency, low-intensity mid-diastolic murmur,
often with presystolic accentuation, is heard at the apex.
Congenital deformities of the mitral valve are rare and constitute Because of the rapid heart rates and displacement of the apex
0.6 percent of postmortems and 0.21 to 0.42 percent of clinical by the dilated hypertensive right ventricle, apical mid-diastolic
series (those excluding associated AVSD). Development of one murmur with presystolic accentuation is rarely observed in
abnormality upstream, during morphogenesis, may result in a congenital mitral stenosis. In some cases, however, a loud,
series of more distal abnormalities owing to disturbance in the high-frequency diastolic murmur may be present and its timing
patterns of flow. Annular hypoplasia of the mitral valve is almost is confirmed only by palpation of the peripheral pulses. The
always associated with hypoplasia of the left ventricle and aortic murmur may diminish in intensity or may be completely absent
stenosis or atresia. VSD is quite common in this setting and when cardiac output is markedly reduced. The murmur of
double outlet right ventricle and tetralogy of Fallot occasionally mitral insufficiency, pulmonary valve insufficiency secondary
occur. When the mitral valve is imperforate, left ventricular to pulmonary hypertension (Graham Steell murmur) and
hypoplasia is inevitable unless there is an associated VSD. findings characteristic of associated cardiac malformations
There is male predilection (in contrast to aquired may be present.
rheumatic mitral stenosis) in congenital mitral stenosis.
Familial recurrence has not been reported in congeital mitral INVESTIGATIONS
stenosis.
Electrocardiography
CLINICAL PRESENTATION AND SYMPTOMATOLOGY
Sinus rhythm is the rule in children, in contrast to theumatic
where atrial fibrillation is observed though first-degree heart
History and Physical Examination
block is common, particularly when the left atrium is greatly
390 Manifestations of symptoms of mitral valve stenosis depend enlarged. Left atrial hypertrophy occurs in about nine-tenths
upon the degree of obstruction to left ventricular inflow, the of patients and right atrial hypertrophy is the rule in patients
with pulmonary hypertension. In mitral stenosis, the mean 27
frontal QRS axis is usually normal or to the right and inferior,
whereas it is generally normal in mitral incompetence. The
Chest Radiography
Whatever the nature of the mitral abnormality, cardiac en
largement tends to be considerable. Splaying of the bronchi
by the enlarged left atrium is particularly prominent.
Infants with imperforate mitral valve or severe mitral
stenosis particularly in the absence of decompression (i.e
without ASD), very occasionally show the ground-glass
appearance of pulmonary edema. More commonly, left atrial
hypertension is manifested in older children by Kerley B lines Figure 13: Chest X-ray in posterioranterior view view in a 12-year-
old girl of Shone’s complex with parachute mitral valve with stenosis
and diversion of blood to the upper lobes (cephalization). In and regurgitation, shows dilated left atrial appendage (LAA), double
infants, the pulmonary trunk and left atrial appendage do not shadow due to right atrial (RA) and grade 2 left atrial (LA) enlargement
form discrete bulges on the upper left cardiac border, which (courtesy: Dr I B Vijayalakshmi)
is consequently straighter than normal. In older children,
prominence of the left atrial appendage is the rule and, in Cross-sectional Echocardiography
patients with pulmonary hypertension, the pulmonary trunk
is prominent (Figure 13). Mitral valve is best visualized in parasternal long-axis,
Straigtening of the left heart border by an enlarged left apical four chamber and two chamber views. Also, it can be
atrial appendage is much less common than in rheumatic interrogated from the atrial aspect in parasternal short-axis
mitral stenosis. Calcification of the mitral valve is also view. Addition of color Doppler further helps to diagnose the
generally absent. These appearances may be profoundly abnormalities. Echocardiography and Doppler is also very
modified by associated abnormalities. If the ascending aorta helpful in providing assessment of the mitral valve apparatus.
is seen on the left upper cardiac border (l-malposed aorta) and Parasternal long-axis view shows the motion of mitral valve
the patient has clinical features of mitral incompetence, then leaftlets for any evidence of doming or prolapse. The chordal
congenitally corrected transposition with tricuspid rather than length, chordal thickening and chordal insertion, etc. are
mitral incompetence is the most likely diagnosis. also well seen in this view. Additional abnormalities of left
ventricular outflow tract like subaortic membrane, tubular
Echocardiography narrowing etc. can be assessed. Apical four chamber view
shows ventricular inflow region for any obstructive membrane
or ring in the atrium, like supramitral ring. The valve annuli
M-mode Echocardiography
can be measured. The valve prolapse is also seen well in this
M-Mode echocardiography provides non-specific evidence view. Apical four chamber view is good for showing dilatation
as to enlargement of the left ventricle, left atrium and right of atria, which may occur secondary to atrioventricular valve
ventricle. Features suggestive of mitral stenosis, include stenosis and/or regurgitation. Parasternal short-axis view with
anterior movement of the mural leaflet in diastole, a sweep from base to apex, shows orientation of commissures,
prolonged time to reach one-fifth of the peak rate in change chordae and papillary muscles including the number of
of left ventricular dimensions and a reduced peak rate of these papillary muscles. Cleft mitral valve and double orifice mitral
changes in dimension. Flattening of the E-F slope is suggestive, valve (Figure 9A and B) are also best diagnosed in this view.
but difficult to recognize in infants with tachycardia. The Addition of color flow mapping is necessary for quantifying
time from closure of the aortic valve to opening of the mitral the regurgitation and in cases with stenosis, to see the level
valve and from left ventricular minimum dimension to mitral of stenosis (Figure 3). The effective orifice size cannot
opening, have proved unhelpful as indicators of congenital be determined by 2D echocardiography when the flow is
mitral stenosis, unlike their use in assessment of acquired interchordal and the valve closure is eccentric. Doppler is also
mitral valvar disease. useful in estimating gradients and valve area. Gradients by 391
http://vip.persianss.ir
5 Doppler may be underestimated due to associated interatrial Magnetic Resonance Imaging
defect or due to poor alignment secondary to multiple levels
of obstruction to left ventricular inflow. Pressure half time Use of Magnetic resonance imaging (MRI) for functional
right and left ventricular obstructive lesions
method is often not reliable in this setting. Planimetry of assessment in congenital heart disease including assessment
the mitral valve orifice in parasternal short-axis view may of mitral regurgitation is an evolving concept. Using this
be the best method for assessment of mitral valve area. The technique, a very good correlation has been found between
normal mitral valve area is 2.4 to 3.6 cm2/m2. In mild mitral measured and calculated regurgitant volumes, with a
stenosis the valve area is reduced to 1.2 to 2.4 cm2/m2; in correlation coefficient of 0.99. MRI provides more reliable
moderate mitral stenosis, mitral valve area is 0.6 to 1.2 cm2/ data with regards to mitral annular diameter, when compared
m2 and in severe mitral stenosis, the valve area is < 0.6 cm2/ to cross-sectional echocardiography. Three-dimensional
m2. Echocardiography is useful for evaluation of associated echocardiography has shown good correlation to MRI
cardiac defects seen in 90 percent of cases with congenital assessment of mitral valve lesions.
mitral valve abnormality.
Cardiac Catheterization
Pulsed and Continuous Wave Doppler Echocardiography
Two-dimensional and Doppler echocardiographic assessment
Doppler echocardiography is a useful modality for assessment of mitral valve stenosis, usually replaces the necessity for
of mitral stenosis. With mitral valvar stenosis, a turbulent cardiac catheterization, unless surgical or interventional
inflow jet is seen, on color Doppler. Both pulse and continuous catheterization management seems indicated. The important
wave Doppler (Figure 14) can be used to calculate the gradient characteristic of mitral obstruction is difference in diastolic
across the valve. In adults and older patients, the pressure half- pressures between the left atrium and ventricle. The high left
time provides an accurate assessment of area, independent atrial pressure seems to seal the valvar mechanism of the oval
of cardiac output. This same technique can be applied to foramen, thus may require transseptal puncture for the same. A
children, although absolute areas calculated in this way are satisfactory pulmonary capillary wedge pressure simultaneous
of little value, because of the wide variation in body surface with the left ventricular pressure may also be used for the same
area. Mean gradients across the valve, as assessed using color (Figure 15). The presence of a diastolic pressure gradient
flow images, have traditionally been used in assessment of between pulmonary artery pressure and mean pulmonary
congenitally malformed hearts, despite the limitation of their capillary wedge pressure suggests the presence of associated
dependency on cardiac output. Color flow Doppler of mitral pulmonary vasoconstriction or pulmonary vaso-occlusive
valve excludes or establishes associated regurgitation and, disease. Administration of oxygen or pulmonary vasodilators
pinpoints the site of obstruction and the pattern of flow across such as nitric oxide and occasional open lung biopsy, may
the valve. This technique also provides valuable clues about be necessary to define the underlying pulmonary vascular
the site of exit of the blood. In a parachute valve there appears pathology and prognosis. Finally, comparison of pulmonary
to be a conical jet of blood, whereas in those with two papillary capillary wedge and left atrial pressure is required if pulmonary
muscles, the jet is more dispersed. vein obstruction is suspected. Routine measurement of wedge
392 Figure 14: Continuous wave Doppler shows both mitral Figure 15: Showing simultaneous left atrial and left ventricular trace
stenosis and regurgitation from a patient with mitral stenosis. Shaded area shows the area
calculation for the mitral valve mean gradient. Note the diastolic
pressure difference between the left atrium and left ventricle
pressures during cardiac catheterization goes a long way for as long as is possible. The exception to this conservative 27
towards detecting otherwise masked mitral stenosis. approach is that for the isolated cleft of the anterior mitral
leaflet, where the results of repair are so good as to justify
http://vip.persianss.ir
5 results seem encouraging, with a low mortality, albeit that as 4. De Lange FJ, Moorman AFM, Anderson RH, et al. Lineage
yet there is no data over the long-term. and morphogenetic analysis of the cardiac valves. Circ Res.
2004;95:645-54.
right and left ventricular obstructive lesions
394
Sec t i on
http://vip.persianss.ir
C hapter
28 Tricuspid Atresia
P Syamasundar Rao
http://vip.persianss.ir
6 Box 1: A unified classification of tricuspid atresia
Courtesy: Reproduced from Rao1 with permission Figure 1: Heart specimen of a patient with muscular type of tricuspid
atresia; the right atrium is opened by cutting through the right atrial
appendage (RAA). Note dimple (arrow) in the floor of the right atrium
with muscle fibers radiating around it. An atrial septal defect (ASD) is
septal defect (VSD), or multiple VSDs and other associated also shown. The impression that one gets from the literature is that this
dimple is present in most cases of tricuspid atresia. Careful inspection
malformations should be described. If one wants to follow of the heart specimen by several investigators suggests that this dimple
the terminology of congenital heart disease proposed and re- is seen in only 29 to 83% of muscular type of tricuspid atresia cases.
emphasized by Van Praagh,21 one could include the remaining Courtesy: Rao PS, et al.23 Am Heart J 1991;122:829
segmental subsets, namely visceroatrial situs and ventricular
loop. Each case could be described by notations SDS, SDD,
SDL and so on as the case may be.21,22 the interatrial communication is obstructive and may form an
aneurysm of the fossa ovalis causing obstruction to the mitral
PATHOLOGIC ANATOMY flow. The left atrium is enlarged and may be more so if the
pulmonary blood flow is increased.
The most common type of tricuspid atresia, muscular variety, The mitral valve is morphologically a mitral valve, usually
is characterized by a dimple or a localized fibrous thickening bicuspid, but its orifice is large and rarely incompetent. The
in the floor of the right atrium (Figure 1) at the expected left ventricle is clearly a morphologic left ventricle with
site of the tricuspid valve14 and constitutes 89 percent of the only occasional abnormalities;25 however, it is enlarged and
cases.16,17 No valvar material can be identified either by gross hypertrophied.
or microscopic examination.14 The VSD may be large, small or non-existent (intact
Other anatomic types, namely, membranous type (6.6%) ventricular septum), or multiple VSDs may be present. When
with the atrioventricular portion of the membranous septum present, it may be:
forming the floor of the right atrium,24,25 valvar type (1%) a. Conoventricular or perimembranous (located inferior to
with minute valve cusps which are fused,15,26,27 Ebstein’s the septal band)
type (2.6%) with Ebstein deformity of the tricuspid valve b. Conal septal malalignment VSD (located in between the
leaflets with fusion of the valve leaflets,10,24,28 common anterosuperior and posteroinferior limbs of septal band)
atrioventricular canal type (0.2%) in which a leaflet of the c. Muscular (located inferiorly when compared to a and b)
common atrioventricular canal completely seals off the only d. Atrioventricular canal type.22
entry into the right ventricle,16,29 and unguarded (0.6%) with In the author’s experience, muscular VSDs are most
muscular shelf30 have been described. For further details the common.31-34 Also, most of these VSDs are restrictive and
reader is referred to our previous reviews.15,17 produce subpulmonary stenosis in the type I patients and
The right atrium is usually enlarged and its wall thickened subaortic stenosis in the type II patients.31-39
and hypertrophied. The interatrial communication, which is The right ventricle is small and hypoplastic; even the largest
necessary for survival, is usually a stretched patent foramen of the right ventricles that are present in patients with large
ovale, sometimes an ostium secundum atrial septal defect and VSDs and/or transposition of the great arteries are smaller
398 rarely an ostium primum atrial septal defect. Occasionally than those in normal. Its size, by and large, is determined
by anatomic type. It may be extremely small so that it may In type I (normally related great arteries) patients with 28
escape detection on gross examination of the specimen as in intact ventricular septum and/or pulmonary atresia (type Ia)
type Ia cases. It can be identified at the right upper aspect of and type II (transposition of the great arteries) patients with
Tricuspid Atresia
the ventricular mass. On occasion, it can be identified only pulmonary atresia (type IIa), the pulmonary blood flow must
on microscopic examination.13,14 However, in most cases the be derived entirely through the ductus. Since, the ductus is
ventricle is a true right ventricle24,40 consisting of: carrying only the pulmonary blood flow, representing 8 to 10
a. A sharply demarcated infundibulum with septal and percent of combined ventricular output in contradistinction
parietal bands to 66 percent in the normal fetus,43,44 the ductus arteriosus
b. A sinus with trabeculae, which communicates with the left is smaller than normal. This and the acute angulation of the
ventricle via a VSD. The inflow region of the right ventricle, ductus at its aortic origin because of reversal of direction of
by definition, is absent although papillary muscles may be ductal flow may render the ductus less responsive to the usual
present occasionally.19 postnatal stimuli.43
The relative position of the great vessels is quite variable In type I patients with moderate to large VSD, there is likely
and has been the basis for classification of this anomaly, to be anterograde blood flow from the left ventricle through
which has been described in the preceding section. The the VSD into the right ventricle, the pulmonary artery, and
ascending aorta may be normal in size or large. Pulmonary ductus arteriosus, whereas there may be retrograde blood flow
outflow obstruction may be either subvalvar or valvar in from the aorta to the ductus arteriosus in the fetus with small
patients with transposition of the great arteries, while in VSD. The larger the VSD, the greater is the probability of
patients with normally related great arteries the pulmonary normal anterograde ductal flow.
obstruction is often at the VSD level although, in a few cases, In type I patients with a small or no VSD, most of the left
subvalvar pulmonary stenosis, narrow tract of the hypoplastic ventricular blood is ejected into the aorta, which is then carried
right ventricle and rarely, valvar pulmonary stenosis may to the entire body including the placenta and lower part of
also be responsible for pulmonary outflow tract obstruction. the body. Thus, the aortic isthmus carries a larger proportion
With pulmonary atresia, either a patent ductus arteriosus or of ventricular output than normal; presumably this is the
aortopulmonary collateral vessels may be present. reason for the rarity of aortic coarctation in these subgroups
A large number of additional abnormalities may be present of tricuspid atresia patients. In type II (transposition) patients
in 30 percent of tricuspid atresia patients.41,42 Significant without significant pulmonary stenosis, because the VSD
among these are persistent left superior vena cava and is usually smaller than the pulmonary valve ring,45 a larger
coarctation of the aorta; the latter is much more common proportion of blood traverses the pulmonary artery and ductus
in type II (transposition) patients. The possible physiologic arteriosus and therefore the isthmic flow decreases, thus
reason for the latter is discussed in the next section. accounting for higher incidence of aortic coarctation and aortic
arch anomalies seen with these types of tricuspid atresia.
PATHOPHYSIOLOGY
Postnatal Circulation
Prenatal Circulation
An obligatory right-to-left shunt occurs at the atrial level in
Tricuspid atresia is not detrimental to normal fetal development. most types and subtypes of tricuspid atresia. Usually, this
In a normally formed fetus, the highly saturated inferior vena shunting is through a patent foramen ovale, but on occasion,
caval blood is preferentially shunted into the left atrium via the secundum or primum atrial septal defects may be present.
patent foramen ovale and from there into the left ventricle and Thus, the systemic and coronary venous blood mixes with
aorta. The superior vena caval blood containing desaturated pulmonary venous return in the left atrium. This mixed
blood is directed towards the tricuspid valve and right ventricle pulmonary, coronary and systemic venous blood enters the
and from there into the pulmonary arteries, ductus arteriosus left ventricle.
and descending aorta. Thus, in a normal fetus, the head, heart In type I (normally related great arteries) patients with a
and upper extremities are supplied with blood at higher PO2 VSD, left-to-right ventricular shunt occurs, thus perfusing the
and the lungs, the lower part of the body and placenta with lungs. In the absence of a VSD, the pulmonary circulation
lower PO2. In tricuspid atresia, both vena caval streams have is derived either via a patent ductus arteriosus or through
to be shunted across the foramen ovale into the left atrium and bronchopulmonary or persistent embryonic aortopulmonary
left ventricle. Therefore, the PO2 differential to various parts of collateral vessels. The presence of either a VSD or other
the body that is normally present does not exist. Whether this means of blood supply to the lungs is crucial for the patient’s
higher PO2 to lungs influences the pulmonary arteriolar smooth survival. The aortic blood flow is derived directly from the left
muscle development or not, is not known.43 Lower than normal ventricle.
PO2 to the brain and upper part of the body does not seem to In type II (d-transposition of the great arteries) patients,
impair their development, at least as observed clinically. the pulmonary blood flow is directly derived from the left 399
http://vip.persianss.ir
6 ventricle. The systemic blood flow is via the VSD and the Pulmonary Blood Flow
right ventricle. In type III, subtype 1 with l-transposition of the
great arteries, the atretic morphologic tricuspid valve is a left- The magnitude of pulmonary blood flow is the major
Congenital Valvar Lesions
sided atrioventricular valve and therefore, in a physiological determinant of clinical features in tricuspid atresia. An infant
sense, it behaves as mitral (left or pulmonary venous atrial) with markedly decreased pulmonary blood flow will present
obstruction. In other type III and type IV patients, the systemic early in the neonatal period with severe cyanosis, hypoxemia
and pulmonary blood flows are determined by the size of the and acidosis. An infant with markedly increased pulmonary
VSD and other associated defects. flow does not have significant cyanosis, but usually presents
with signs of heart failure. Although there is some overlap,
Other Physiologic Principles patients with decreased pulmonary flow usually belong to type
I (normally related great arteries) and those with increased
Arterial Desaturation pulmonary blood flow are usually type II (transposition of the
great arteries) and occasionally type Ic.
Because of complete admixture of the systemic, coronary and The magnitude of pulmonary blood flow in an unoperated
pulmonary venous returns in the left atrium and left ventricle, patient is dependent upon the degree of obstruction of
systemic arterial desaturation is always present. The oxygen the pulmonary outflow tract and patency of the ductus
saturation is proportional to the magnitude of the pulmonary arteriosus. The pulmonary outflow obstruction is valvar or
blood flow.43,46 The data from our study patients are plotted in subvalvar in type II patients and valvar, subvalvar or at VSD
Figure 2; the pulmonary to systemic blood flow ratio (Qp : Qs) level in type I patients. In our own experience with several
which represents the pulmonary blood flow has a curvilinear series of tricuspid atresia, we found the obstruction to be
relationship with the arterial oxygen saturation. A Qp : Qs of located most commonly at the VSD level.31-34,37,38 When
1.5 to 2.5 appears to result in an adequate oxygen saturation.46 the VSD is large and non-restrictive and the pulmonary
Further increase in Qp : Qs does not result in better oxygen valve not stenotic, the pulmonary flow is proportional to
saturation, but may subject the left ventricle to larger volume the pulmonary to systemic vascular resistance ratio. When
overloading and, therefore is not advisable.46 a systemic to pulmonary artery shunt has been performed,
the pulmonary blood flow is proportional to the size of the
anastomosis.
Tricuspid Atresia
place in patients with tricuspid atresia. Closure of the ductus Recurrent respiratory tract infection and failure to thrive is
arteriosus occurring in early neonatal period may result in another mode of presentation. The majority of these patients
severe hypoxemia. The size of the interatrial communication belong to type IIc, although a small number of patients may
may diminish either in absolute terms or relative to the volume be of type Ic. The association of aortic coarctation with type
of the systemic venous return and cause systemic venous II patients has already been mentioned and coarctation, when
congestion and may require atrial septostomy. The ventricular present, makes them vulnerable to early cardiac failure.
septal defect may close spontaneously,31-39 causing pulmonary Examination reveals tachypnea, tachycardia, decreased
oligemia and hypoxemia in type I patients or subaortic femoral pulses (when associated with aortic coarctation, but
obstruction in type II patients. Such VSD closures occur over without significant-sized patent ductus arteriosus), minimal
a period of months and years. The reader is referred to other cyanosis, prominent neck vein pulsations and hepatomegaly.
publications17,38 for further discussion. Prominent ‘a’ waves in jugular veins and/or presystolic
hepatic pulsations may be observed with associated inter-
CLINICAL FEATURES atrial obstruction. The precordial impulses are increased and
hyperdynamic. The second heart sound may be single or split.
Approximately one-half of the patients with tricuspid atresia A holosystolic murmur of VSD is usually heard at the left
manifest symptoms on the 1st day of life and 80 percent would lower sternal border. An apical mid-diastolic murmur may be
be symptomatic by the end of the 1st month of life.9,51 As heard. Clear-cut signs of congestive cardiac failure are usually
previously mentioned, the magnitude of pulmonary blood flow present.
determines the clinical features. Two modes of presentation
are recognized—those with decreased pulmonary blood flow NON-INVASIVE EVALUATION
and those with increased pulmonary blood flow.
Chest Roentgenogram
Decreased Pulmonary Blood Flow
Roentgenographic picture is, by and large, dependent upon
Infants with pulmonary oligemia present with symptoms of the total pulmonary blood flow. In patients with diminished
cyanosis within the first few days of life; more severe the pulmonary flow (the majority of infants will fall into this
pulmonary oligemia, the earlier is the clinical presentation. category), the heart size is either normal or minimally
These hypoxemic infants may have hyperpnea and acidosis enlarged, whereas in those with increased pulmonary blood
if the pulmonary blood flow is markedly decreased. The flow, the heart size is moderately to severely enlarged. Several
majority of these infants belong to type Ib. Patients with patterns of cardiac configuration, namely ‘characteristic’
pulmonary atresia (Subgroup a) irrespective of the type will tricuspid atresia appearance,52 coeur en sabot configuration,53
also present with early cyanosis, especially when the ductus ‘egg-shaped’,19 ‘bell-shaped’,54 and square11 heart have been
begins to close. Hypoxic spells are not common in the neonate described, but in the author’s experience and that of others,19
although the spells can occur later in infancy. there is no consistent pattern that would be diagnostic of
Physical examination reveals central cyanosis, tachypnea tricuspid atresia. There may be concavity in the region
or hyperpnea, normal pulses, prominent ‘a’ wave in the jugular of pulmonary artery segment in patients with pulmonary
venous pulse (if there is significant interatrial obstruction), oligemia and small pulmonary artery. The right atrial shadow
and no hepatic enlargement (presystolic hepatic pulsations may be prominent.
may be felt if there is severe interatrial obstruction). Quiet Right aortic arch may be present in approximately 8
precordium and absence of thrills is usual. The second heart percent of patients with tricuspid atresia19 and is less common
sound is usually single. A holosystolic murmur, suggestive of than that observed in patients with tetralogy of Fallot (25%)
VSD may be heard at the left lower or left midsternal borders. and truncus arteriosus (40%). An unusual contour of the left
No diastolic murmurs are heard. In patients with associated border of the heart suggestive of 1-transposition may be
pulmonary atresia, no murmurs are usually heard, although in seen in association with type III, subtypes 1 and 5 tricuspid
an occasional patient, a continuous murmur of patent ductus atresia.55
arteriosus may be heard. Clinical signs of congestive heart The greatest use of the chest roentgenogram is its ability
failure are notably absent. to categorize babies into those with decreased pulmonary
vascular markings and into those with increased pulmonary
Increased Pulmonary Blood Flow vascular markings. Often, this is all that is necessary to make
a correct diagnosis once a history, physical examination
Infants with pulmonary plethora usually present with signs and electrocardiogram (see the next section) have been 401
of heart failure within the first few weeks of life, although obtained.55
http://vip.persianss.ir
6 Electrocardiogram pattern.58 Normal (0-+90°) or right axis deviation is present
in a minority of patients and most of these patients belong to
The electrocardiogram (ECG) can be virtually diagnostic type II or III anatomy. It has been suggested that the ASV may
Congenital Valvar Lesions
of tricuspid atresia in a patient suspected to have a cyanotic be related to destructive lesions in the left anterior bundle,56
congenital heart defect. Right atrial hypertrophy, an abnormal, fibrosis of left bundle branch,59 abnormal distribution of the
superiorly oriented major QRS vector (so called left axis conduction system (unusually long right bundle branch and
deviation) in the frontal plane, left ventricular hypertrophy origin of left bundle branch very close to the nodal-His bundle
and diminished right ventricular forces (Figure 3) are junction),60-62 a small right ventricle or a large left ventricle.57
characteristic findings. Ventricular activation data from our group58,63 suggested that
The right atrial hypertrophy, manifested by tall, peaked this characteristic QRS pattern in tricuspid atresia is produced
P waves in excess of 2.5 mm, is present in the majority of by interaction of several factors, the most important being
the patients with tricuspid atresia.56 Although it has been the right-to-left ventricular disproportion and asymmetric
suggested that the amplitude of P wave in lead II is directly distribution of the left ventricular mass favoring the superior
proportional to the interatrial pressure difference and inversely wall.
proportional to the size of the interatrial communication, Regardless of the frontal plane mean QRS vector
detailed analysis of these parameters did not suggest a orientation, electrocardiographic criteria for left ventricular
consistent relationship.9,57 A double peak, spike and dome hypertrophy are present in the vast majority of patients. This
configuration of the P wave, referred to as ‘P-tricuspidale’56 may be manifested by increased (above 95th percentile) S
may be present. The first taller peak is contributed by the right waves in right chest leads and R waves in left chest leads or by
atrial depolarization and the second smaller peak is presumed ‘adult progression’ of the QRS in the chest leads in the neonates
to be due to left atrial depoloarization.56,58 and infants. ST-T wave changes suggestive of left ventricular
Abnormal, superiorly oriented major QRS vector (ASV), strain is present in 50 percent of patients.58 The reason for left
more popularly called left axis deviation, between 0 to –90° in ventricular hypertrophy is the anatomic nature of the lesion
the frontal plane is present in the majority of the patients with with the resultant hemodynamics as well as lack of opposition
tricuspid atresia. ASV is present in excess of 80 percent of of the forces of left ventricular activation by the hypoplastic
patients with type I anatomy (normally related great arteries) right ventricle. Occasionally, biventricular hypertrophy may
while only less than 50 percent of patients with type II and be present and majority of these patients belong to type II or
type III anatomy show such a typical electrocardiographic III anatomy with good-sized right ventricle.
402
Figure 3: Twelve electrocardiogram showing an abnormal, superiorly oriented mean QRS vector in frontal plane (–45°, left axis deviation), left
ventricular hypertrophy and diminished anterior (R waves in leads V1 and V2) and rightward (S waves in leads V5 and V6) forces. Tall P waves
are also seen in several leads, indicative of right atrial enlargement. This electrocardiogram is highly suggestive of tricuspid atresia
Diminished R waves in right chest leads and S waves in be identified as pulmonary or aortic by following the great 28
left chest are related to right ventricular hypoplasia. vessel until the bifurcation of the pulmonary artery or arch
Vectorcardiographic features closely resemble the scalar of the aorta is seen; this will help to decide, whether there
Tricuspid Atresia
electrocardiogram, but vectorcardiography is no longer is associated transposition of the great arteries. Suprasternal
available for routine use. notch imaging will be of use in demonstrating coarctation of
the aorta, which is often seen in type II patients.
Echocardiogram Contrast echocardiography with two-dimensional imaging
will clearly demonstrate sequential opacification of the right
M-mode echocardiographic features include a large left atrium, left atrium, left ventricle and then the right ventricle.
atrium (usually proportional to the magnitude of pulmonary However, contrast study is neither necessary nor recommended
blood flow), dilated left ventricle with normal to decreased for making the diagnosis.
left ventricular shortening fraction, a large posterior Doppler examination is also useful in the evaluation of
atrioventricular valve in continuity with posterior semilunar tricuspid atresia patients. The obligatory right-to-left shunt
valve and a small right ventricle.55,64 The pulmonary valve may across the atrial septal defect can be demonstrated by placing
or may not be recorded. The tricuspid valve is conspicuously pulsed Doppler sample volume on either side of the atrial
absent.55 Tricuspid valve-like echoes of low amplitude may septum and by color flow Doppler. Left-to-right shunting
be recorded occasionally and this should not exclude the across the VSD may also be demonstrated by Doppler. In
diagnosis of tricuspid atresia.65 type I (normally related great arteries) patients, the VSD
Two-dimensional echocardiography, apart from showing peak Doppler velocity is helpful in estimating the size of the
enlarged right atrium, left atrium and left ventricle and a small VSD; the higher the velocity, the smaller is the VSD. Right
right ventricle demonstrates the atretic tricuspid valve directly. ventricular and pulmonary arterial pressure may also be
In the most common muscular type, a dense band of echoes estimated using modified Bernoulli equation:
is seen at the site, where tricuspid valve should be55,66 and RV/PA systolic pressure = systolic BP – 4V2
the anterior leaflet of the detectable atrioventricular valve is where, RV is right ventricle, PA is pulmonary artery, BP is arm
attached to the left side of interatrial septum (Figure 4). Apical systolic blood pressure and V is VSD peak Doppler velocity.
and subcostal four-chambered views are best to demonstrate In the presence of pulmonary hypertension or severe
the anatomy. infundibular or valvar pulmonary stenosis, the above VSD
Atrial and ventricular septal defects can also be Doppler velocities are not indicative of the size of the VSD. In
demonstrated by 2D echocardiography. Semilunar valves can type II (d-transposition) patients, high velocity is suggestive
of subaortic obstruction.
Interrogation of right ventricular outflow tract in type
I patients and pulmonary artery region in type II patients
may reveal pulmonary or subpulmonary stenosis; higher the
velocity, more severe is the obstruction.
Doppler evaluation of descending aortic flow is helpful in
demonstrating aortic coarctation.
In summary, delineation of the majority of anatomic and
physiologic issues related to tricuspid atresia is feasible by
M-mode, two-dimensional and Doppler (pulsed, continuous
wave and color) echocardiography.
http://vip.persianss.ir
6 Cardiac Catheterization by an increase of 6 percent or more in O2 saturation from the
superior vena cava to the right atrium in two or more sets of
The diagnosis of tricuspid atresia based on clinical, saturations in 29 of 50 (58%) catheterizations in which the data
Congenital Valvar Lesions
electrocardiographic and echocardiographic features is were adequate.50 However, in the shunt group, the left atrial ‘v’
relatively simple and cardiac catheterization and selective waves were equal to or higher than the right atrial ‘v’ waves
cineangiography, rarely, if ever, are essential for establishing accounting for the left-to-right atrial shunting. Simultaneous
the diagnosis.46 Even neonates with significant arterial pressure recordings from the left atrium and the right atrium
desaturation need not undergo cardiac catheterization and with isosensitized miniature pressure transducers mounted 5
selective cineangiography; the diagnosis of tricuspid atresia cm apart, revealed a higher pressure in the left atrium than
is usually made on the basis of clinical and non-invasive in the right atrium during atrial diastole (Figure 5). Based on
evaluation, particularly echo-Doppler studies. Catheterization findings of that study,50 it was concluded that:
may be indicated prior to bidirectional Glenn or Fontan 1. left-to-right shunt across the atrial septal defect occurs
operations. If catheterization is performed, the following frequently in tricuspid atresia
features may be found. 2. The left-to-right shunt is a result of instantaneous pressure
difference between atria and such shunts are ‘physiologic’.
Catheter Course The pulmonary venous saturations are usually in the normal
range. A significant decrease in left atrial saturation is expected
Because of atretic tricuspid valve, the right ventricle cannot because of obligatory right-to-left shunting across the patent
be directly catheterized from the right atrium. The catheter foramen ovale. Falsely high or falsely low saturations may
can easily be maneuvered into the left atrium across the patent be measured in the left atrium because of streaming. The left
foramen ovale. The catheter may follow a similar course in ventricular saturations are usually well mixed and are more
patients with pulmonary atresia (or severe stenosis) with reliable. The saturations in the left atrium and left ventricle as
intact ventricular septum and hypoplastic right ventricle or well as those in the right ventricle, the pulmonary artery and
severe tricuspid stenosis. Inability to enter the right ventricle the aorta are identical. Systemic arterial desaturation is always
from the right atrium is not necessarily diagnostic of tricuspid present and the extent of desaturation is proportional to the
atresia, but in experienced hands, it is highly suggestive of Qp : Qs (Figure 2).46
tricuspid atresia. The vena caval, left atrial, left ventricular and aortic
From the left atrium, the catheter can easily be manipulated oxygen saturations are usually lower in type I patients than
into the left ventricle. With the previous conventional those in type II patients.46 This is presumably related to greater
catheters, the left ventricle is the farthest structure that could preponderance of pulmonary oligemia in type I patients.
be catheterized in tricuspid atresia. However, with the use of
balloon-tipped catheters and other maneuvers using guide
wires, the aorta, the right ventricle and the pulmonary artery
can be catheterized, particularly in older infants and children.
But in neonates, once an adequate left ventricular angiogram
is performed, we will terminate the procedure because
further manipulation of the catheter may precipitate spells or
arrhythmia and the additional information obtained may not
be of much value.
In infants with clinical and/or blood pressure evidence
for aortic arch obstruction, retrograde arterial catheterization
(using percutaneous Seldinger technique or transumbilical
route) may be necessary especially, if the aortic arch anatomy
is not clearly demonstrated by left ventricular angiography.
Oxygen Saturations
Systemic venous oxygen saturations are usually diminished
Figure 5: Simultaneous pressures from the left atrium (LA) and right
and the extent of decrease is related to systemic arterial atrium (RA) are recorded by means of high fidelity miniature pressure
desaturation and the severity of congestive heart failure. transducers mounted on a catheter 5 cm apart. Note higher RA
Because of the obligatory right-to-left shunting across pressure during atrial systole and higher LA pressure during atrial
diastole; the later finding may help explain the “physiologic” left-to-
the patent foramen ovale, it is generally believed that the
right shunting at atrial level in tricuspid atresia patients. Courtesy: Rao
right atrial saturations are similar to vena caval saturations. PS: Br Heart J 1983;49:345.50 a = ‘a’ wave; ECG = Electrocardiogram;
404 However, we found left-to-right atrial shunting, represented v = ‘v’ wave
Pressures 28
The right atrial mean pressure is minimally elevated. In the
Tricuspid Atresia
absence of interatrial obstruction, it is dependent upon the left
ventricular end-diastolic and left atrial pressure. The right atrial
‘a’ waves are usually prominent. A mean pressure gradient of 5
mm Hg or more across the foramen ovale in favor of the right
atrium and giant ‘a’ waves in the right atrium are indicative of
an obstructive foramen ovale. However, when there is marked
elevation of the left ventricular end-diastolic pressure and left
atrial pressure, lack of pressure gradient across the interatrial
communication does not exclude inter-atrial obstruction.46
The left ventricular end-diastolic pressure is usually
normal and increases with increasing Qp : Qs and decreasing
left ventricular function.
The right ventricular pressure is proportional to the size
of the ventricular septal defect in type I patients, while it is at Figure 6: Selected frame from a posteroanterior view of a right atrial
systemic level in type II patients. Systolic pressure gradient (RA) angiogram in a child with tricuspid atresia showing successive
across the VSD may be seen if it is restrictive. Pulmonary opacification of the left atrium (LA) and left ventricle (LV). There was no
direct and immediate opacification of the right ventricle; the negative
artery pressure may be normal or increased depending upon shadow, so called right ventricular window is shown with an arrow
the size of the VSD in type I patients or upon the presence
or absence of subvalvar or valvar stenosis in type II patients.
Aortic pressures are usually normal. If coarctation of the aorta
is present, systolic hypertension and pressure gradient across ventricular window (Figure 6) seen in earlier frames of right
the coarctation may be present. atrial angiography is due to failure of direct right ventricular
filling, but the right ventricle is seen subsequent to left
Calculated Variables ventricular opacification. Although this area can be profiled
well in the elongated right anterior oblique and the four-
Systemic and pulmonary blood flows and resistances and chamber views,71 posteroanterior view is most commonly
shunts can be calculated by the Fick principle either by used to demonstrate these signs and is perhaps far superior.19
measuring oxygen consumption or by assuming it from tables The above described signs were initially thought to
of normal values.46 The principles and methods of calculation be pathagnomonic of tricuspid atresia, but it is now well-
have been detailed elsewhere46 and will not be discussed here. recognized that such appearance can be seen in patients with
Although most of the calculations can be performed, Qp : Qs is pulmonary atresia or severe stenosis with intact ventricular
the most useful calculated value. The Qp : Qs is diminished in septum and large right-to-left shunting at atrial level, tetralogy
type I hypoxemic infants with small or no VSD. It is markedly of Fallot with atrial septal defects (the so called pentology of
increased in type I patients with moderate to large VSDs and Fallot) and total anomalous pulmonary venous return to the
in most patients with type II anatomy. coronary sinus.19,71
Other calculated variables such as pulmonary vascular Although the right atrial angiography is helpful in the
resistance,46 preoperative catheterization index68 and trans- diagnosis, selective left ventricular angiography (Figure 7)
pulmonary gradient (pulmonary artery mean pressure—left should also be performed in order to delineate the anatomy
atrial mean pressure) are useful measures in the pre-Fontan and size of the left and right ventricles, size and type of
evaluation. ventricular septal defects(s), relationship of great arteries and
the source of pulmonary blood flow. Frontal and lateral views
Cineangiography of the ventriculogram are most commonly used although left
anterior oblique view, long axial oblique view or a four-
Since the initial description by Campbell and Hills69 and chambered view may help delineate desired anatomic detail.
Cooley et al,70 two signs, namely, ‘typical sequence of In most neonates, selective right atrial and left ventricular
tricuspid atresia’ and ‘right ventricular window’, on right angiograms are all that will be necessary. Selective
atrial angiography have been very helpful in the diagnosis of antegrade or retrograde aortography to demonstrate either
tricuspid atresia. Selective right atrial or superior vena caval the pulmonary arterial anatomy or aortic coarctation may
angiogram reveals successive opacification of the left atrium occasionally be needed. For additional discussion on
and left ventricle without immediate opacification of the right angiography in tricuspid atresia, the reader is referred to
ventricle (Figure 6). The negative shadow, so called right other publications.18,71 405
http://vip.persianss.ir
6 During the process of identification, transfer to a pediatric
cardiology center, initial work-up and palliative surgery as
well as following surgery, neutral thermal environment, normal
Congenital Valvar Lesions
Tricuspid Atresia
used in the palliation of pulmonary oligemia. Because of the atresia,38,42 only two with type I anatomy required pulmonary
problems associated with central shunts, Blalock-Taussig artery banding and there are only a few cases reported in the
type of shunt is preferred. At present, a modified Blalock- literature that required pulmonary artery banding. If optimal
Taussig shunt with a Gore-Tex graft interposed between anticongestive therapy with some time delay does not produce
the subclavian artery and the ipsilateral pulmonary artery, adequate relief of symptoms,42 pulmonary artery banding
described by deLeval84 appears to be the preferred choice in should be considered in type I patients; perhaps a serious
most institutions for palliation of the neonate and young infant consideration for using absorbable band material should be
with pulmonary oligemia. given.89-91 In those that did not have pulmonary artery banding
Enlargement of VSD and/or resection of right performed, careful follow-up studies with measurement
ventricular outflow tract obstruction has been performed, of pulmonary artery pressure and appropriate treatment are
and recommended by Annecchino and his colleagues85 as necessary to prevent pulmonary vascular obstructive disease.
a palliative procedure to augment the pulmonary blood In type II patients, banding of the pulmonary artery should
flow. This is an ingenious approach and attacks the site of be performed once the infant is stabilized with anticongestive
obstruction rather than bypassing it. However, it is an open therapy. If there is associated coarctation of the aorta or aortic
heart procedure and may not be feasible or necessary in the arch interruption or hypoplasia, adequate relief of the aortic
neonatal period.42 Placement of a stent in the ductus, to keep obstruction should be provided concurrent with pulmonary
it open to provide pulmonary flow is an attractive option,86,87 artery banding and the patent ductus arteriosus should be
but, because of limited experience and technically demanding ligated, if present. The importance of PGE1 administration
nature of the procedure, it currently is not a therapeutic in temporarily relieving aortic obstruction and thereby
procedure of choice. If the predominant obstruction is at the controling congestive heart failure has already been alluded.
pulmonary valve level, balloon pulmonary valvuloplasty88 The role of balloon dilation angioplasty of the coarctation80-82
may be considered. in these complicated lesions has not yet been completely
In conclusion, despite the availability of many types of delineated. Because of higher risk for poor outcome in patients
palliative procedures to increase pulmonary blood flow, most with transposition and those requiring pulmonary artery
of them are either not advisable or effective and if effective, banding and/or aortic arch repair, early, adequate appropriate
may produce serious complications to deter from performing a intervention is desirable.
successful Fontan-Kreutzer procedure subsequently. Modified
Blalock-Taussig anastomosis84 has the least number of long- Intracardiac Obstruction
term complications, but at the same time, preserves suitable
anatomy for subsequent corrective procedures. Therefore, it Intracardiac obstruction can occur at two different levels,
is recommended as the procedure of choice for palliation of namely, patent foramen ovale and VSD.
tricuspid atresia patients with decreased pulmonary blood flow. Interatrial obstruction: Since the entire systemic venous
return must egress through the patent foramen ovale, it should
Increased Pulmonary Blood Flow be of adequate size to accommodate it. A mean atrial pressure
difference of 5 mm Hg or more with very prominent ‘a’ waves
Infants with a modest increase in pulmonary blood flow do (15 to 20 mm Hg) in the right atrium is generally considered
not have any significant symptomatology and indeed are less to represent obstructed interatrial septum.9,46 Balloon atrial
cyanotic than the pulmonary oligemic patients. Markedly septostomy,92,93 if unsuccessful blade atrial septostomy,93-95
increased pulmonary blood flow, however, can produce and rarely surgical atrial septostomy may be necessary to
congestive heart failure. Only type Ic and Type IIc patients, relieve the obstruction. Significant interatrial obstruction
i.e. without associated pulmonary stenosis, will fall into the requiring atrial septostomy in the neonate is rare and unusual
category of pulmonary plethora. A majority of these patients although this can be a significant problem later in infancy.42,92
will have type II anatomy and will usually manifest during Interventricular obstruction: Spontaneous closure of the
early infancy. VSD causing severe pulmonary oligemia in type I patients
In type I patients, aggressive anticongestive measures and subaortic obstruction in type II patients can occur;31-39
should be promptly instituted. The natural history of the this usually takes months to years to develop. Management
VSD has been well documented in this group;31-38 the VSD of spontaneous closure of the VSD causing severe pulmonary
becomes smaller and patients with pulmonary plethora will, in oligemia in type I patients is as alluded to in the preceding
due course, develop pulmonary oligemia, requiring palliative section on pulmonary oligemia. Partial spontaneous closure of
surgical shunts. These patients can also develop right the VSD in type II patients causes subaortic obstruction,33,34,38
ventricular outflow tract obstruction with resultant decrease which should be relieved or bypassed lest the resultant left 407
http://vip.persianss.ir
6 ventricular hypertrophy pose increased risk at the time of cavopulmonary diversion,74 bidirectional Glenn,99 intra-atrial
the Fontan procedure.96 The obstruction must be tackled at tunnel74 and extracardiac conduit100 to divert the inferior vena
the time of either a bidirectional Glenn or a modified Fontan caval blood into the pulmonary artery, staged Fontan101,102
Congenital Valvar Lesions
operation. Resection of the conal muscular septum,97,98 thus and fenestrated Fontan.103-105
enlarging the VSD, is a direct approach, although concern
for development of heart block and spontaneous closure of Physiologically Corrective Surgery
the surgically produced VSD remains.38 Alternatively, the
VSD, right ventricle and aortic valve may be bypassed by Operations that divide the pulmonary and systemic venous
anastomosis of the proximal stump of the divided pulmonary returns (Fontan-Kreutzer) are feasible for most patients
artery to the ascending aorta (Damus-Kaye-Stansel) at the with tricuspid atresia. Hydrodynamic studies by de Leval
time of bidirectional Glenn (or Fontan) operation. For further and colleagues74 concluded that the right atrium has no
discussion of this subject, the reader is referred elsewhere.33,34,38 efficient pump function; pulsations in non-valved circulation
generate turbulence with consequent decrease in net flow and
Medical Management Following Palliative Surgery energy losses occur in the non-pulsatile chambers, corners
and obstructions. To address this issue, they proposed total
Problems encountered with tricuspid atresia patients are similar cavopulmonary anastomosis. The advantages of this procedure
to those found in other types of cyanotic cardiac malformations. are technical simplicity, maintenance of low right atrial and
Appropriate monitoring for and treatment of relative anemia, coronary sinus pressure and reduction in risk of formation of
polycythemia, coagulopathy and hyperuricemia should be atrial thrombi and perhaps reduction in arrhythmias.
undertaken. The risks for development of a cerebrovascular In the bidirectional Glenn procedure, the upper end of the
accident or brain abscess are similar to those seen with divided superior vena cava is anastomosed end to side to the
other cyanotic anomalies. Antibiotic prophylaxis before any superior aspect of the undivided right pulmonary artery, thus
bacteremia producing procedures or surgery is indicated, as diverting the superior vena caval blood into both right and
is routine immunization plus consideration for Palivizumab left pulmonary arteries. Hemodynamic advantages associated
(for prevention of RSV infection in infancy), polyvalent with the bidirectional Glenn include, improved effective
pneumococcal vaccine or influenza vaccine. pulmonary flow, reduced total pulmonary flow and less left
ventricular volume overloading.
Historical Aspects of Corrective Surgery Staging the Fontan appears to decrease overall mortality,
for Tricuspid Atresia presumably related to improving the ventricular function
by correcting afterload mismatch associated with one stage
Fontan72 and Kreutzer73 concurrently described physiologi Fontan. At the present time, staged Fontan with bidirectional
cally corrective operations for tricuspid atresia in 1971. Glenn initially followed later by extracardiac conduit
Fontan operation, as described by Fontan consisted of diversion of the inferior vena caval blood into the pulmonary
superior vena cava—right pulmonary artery shunt (classical artery appears to be the preferred approach.
Glenn), anastomosis of the proximal end of the divided right As mentioned, currently preferred ‘corrective’ procedure
pulmonary artery to the right atrium directly or by means of is staged total cavopulmonary anastomosis. A bidirectional
an aortic homograft, closure of the atrial defect, insertion of a Glenn procedure (superior vena cava to pulmonary artery
pulmonary valve homograft into the inferior vena caval orifice anastomosis) may be performed around the age of 6 months.
and ligation of the main pulmonary artery, thus bypassing Preoperative catheter evaluation to define the pulmonary
the right ventricle completely;72 it would appear that Fontan artery pressure and anatomy and to exclude a persistent left
concept was to use the right atrium as a pump. Kreutzer’s superior vena cava (because it may divert blood away from
operation consisted of direct anastomosis of the right atrial the pulmonary arteries) prior to bidirectional Glenn surgery
appendage with the pulmonary artery or through a pulmonary should be undertaken. At the time of bidirectional Glenn
homograft and closure of the atrial septal defect.73 He did not procedure, stenoses, if any of the pulmonary artery should
perform a Glenn procedure nor insert a prosthetic valve into be repaired. Issues related to subaortic obstruction and mitral
the inferior vena cava. It appears that Kreutzer’s concept was valve regurgitation should also be addressed.
that the right atrium may not function as a pump and that the When the patient reaches the age and size (approximately
left ventricle is the only ‘suction’ pump in the system. Many 15 kg) suitable for Fontan-Kreutzer operation, diversion of
modifications of these procedures have been suggested, as inferior vena caval blood into the pulmonary artery either
reviewed elsewhere by us.75,76 Based on these reviews it by a lateral tunnel or extracardiac conduit is recommended.
would appear that direct atriopulmonary anastomosis (without At the present time extracardiac conduit diversion of inferior
a valved conduit) became the standard procedure for most vena caval blood into the pulmonary artery is preferred by
tricuspid atresia patients. Over a period of time, a number most surgeons. Immediately prior to Fontan conversion,
408 of other concepts/procedures evolved and these include total cardiac catheterization should be undertaken to ensure normal
anatomy and pressure of the pulmonary artery as well as be treated with appropriate pharmacologic therapy. In a 28
normal left ventricular end-diastolic pressure. At the same patient without adequate control, electrophysiologic study and
time, aortopulmonary collaterals should be evaluated by surgical or transcatheter ablation may be needed.108 Revision
Tricuspid Atresia
means of selective subclavian artery and descending thoracic of the Fontan pathway to a cavopulmonary connection with
aortic angiography. If collateral vessels are present, they elimination of the enlarged right atrium has been considered
should be occluded with coils or devices, as appropriate. an alternative solution. Sick sinus node syndrome and
The criteria outlined by Choussat and associates106 have atrioventricular block occur in some children and may require
been modified or exceeded by many groups of workers. pacemaker therapy. Ventricular arrhythmia is less frequent.
These factors, when present, would make the Fontan-Kreutzer Symptoms and signs indicative of obstruction to Fontan
operation a high-risk procedure and should be identified at pathways should be promptly investigated. Poor echo windows
the time of preoperative evaluation. They include elevated make non-invasive evaluation difficult and cineangiography
pulmonary artery pressure (mean pressure >18 mm Hg) or or imaging studies (CT or MRI) may become necessary.
resistance (> 4 Wood units/m2), distorted or small (McGoon Obstructive lesions should be treated with balloon angioplasty,
ratio of 1.8 or less) pulmonary arteries, poor left ventricular stenting or even surgery, as necessary.
function (end-diastolic pressure above 12 mm Hg), significant A persistent shunt may be due to intentional fenestration
mitral regurgitation, subaortic obstruction and severe left created at the time of Fontan or a residual atrial septal
ventricular hypertrophy. With one or more of these risk factors, defect. If significant hypoxemia is present, the residual shunt
physiologically corrective procedures of the Fontan type may should be closed, preferably by a transcatheter device.109,110
carry significant risk. In such high-risk Fontan-Kreutzer patients, Test occlusion109 of the defect to ensure that adequate
leaving open a small atrial septal defect to allow decompression cardiac output will be maintained after defect occlusion is
of the right atrium in the immediate postoperative period with a recommended. Closing the defect has beneficial effect in
plan to close the defect later has been proposed.103-105 The atrial preventing paradoxical embolism and stroke.
defect is closed by a preplaced suture103,104 or by transcatheter Recurrent pleural effusion, liver dysfunction and protein-
techniques.105 Significant improvement in postoperative pleural losing enteropathy have occurred in a small number of
effusions, systemic venous congestion and higher cardiac index patients. Protein-losing enteropathy carries a high (75%)
and possibly shorter hospitalization have been the beneficial mortality.110,111 The cause of protein-losing enteropathy is not
effects of the fenestration, but at the expense of systemic arterial well-understood, but appears to be related to loss of protein
hypoxemia. However, some surgeons prefer fenestration for all in the bowel by lymphatic distention secondary to increased
patients. Six to twelve months later, transcatheter closure of systemic venous pressure, although this can occur in patients
the fenestration may be undertaken if the fenestration did not with reasonably ‘normal’ pressures for the Fontan procedure.
spontaneously close. Symptoms usually appear 6 months following the Fontan-
In patients with transposition of the great arteries, early Kreutzer procedure or later. They manifest diarrhea, edema,
pulmonary artery banding, treatment of aortic coarctation, ascites and pleural effusion. Serum hypoalbuminemia and
and relieving or bypassing subaortic obstruction should also increased α1-antitrypsin in the stool are present. One should
be incorporated into the treatment plan. carefully scrutinize for evidence of obstruction in the Fontan-
Kreutzer pathway. If such is found it should be relieved.112
Follow-up after Corrective Operation Supportive therapy with medium-chain triglyceride diet
and parenteral albumin supplementation may be instituted.
Close follow-up after correction is indicated. Some patients A number of treatment regimens including prednisone,
may need inotropic and diuretic therapy. Afterload reduction regular high-molecular-weight heparin, low-molecular-weight
with an angiotensin-converting enzyme inhibitor is used by heparin, elementary diet, calcium replacement, somatostatin,
some cardiologists to improve left ventricular output. Because high-dose spironolactone, sildenafil and resection of localized
of the potential for development of thrombi in the right atrium, intestinal lymphangectasia (if demonstrated) have been
anticoagulants are routinely used by most cardiologists. attempted, all with variable success.112 Since protein-losing
I recommend platelet-inhibiting doses of Aspirin, others enteropathy appears to be a fatal complication of the Fontan
advocate Warfarin anticoagulation. procedure, aggressive management is suggested. Apart from
Most patients do well after operation.107 However, some excluding and addressing obstructions and residual shunts in
problems have been seen after corrective surgery namely, the Fontan circuit plus other conventional treatment options,
arrhythmia, obstructed pulmonary outflow pathways, consideration for:
persistent shunts and systemic venous congestion including 1. Reduction of right atrial pressure by creation of an atrial
protein-losing enteropathy. septal defect (Brockenbrough puncture plus static dilation
Supraventricular arrhythmias (atrial flutter or fibrillation, of the atrial septum)
paroxysmal supraventricular tachycardia) may be seen, 2. Right atrial and left ventricular (atrioventricular sequential)
particularly with older types of Fontan operation. They may pacing,113,114 409
http://vip.persianss.ir
6 3. Conversion of atrioventricular Fontan to total 4. Rao PS. Terminology: is tricuspid atresia the correct term to
cavopulmonary anastomosis,115,116 and/or use? In: Rao PS (Ed). Tricuspid Atresia, 2nd edition, Mount
4. Cardiac transplantation117,118 should be given. However, Kisco, NY, Futura Publishing Co. 1992.p.3.
Congenital Valvar Lesions
most patients do well after the Fontan-Kreutzer procedure. 5. Rashkind WJ. Tricuspid atresia: A historical review. Pediat
Cardiol. 1982;2:85.
6. Kreyseg FL. Die Krankheiten des Herzens. Dritte Thies. 181.p.
PROGNOSIS 104.
7. Editors: London Medical Review 1812;5:262.
Untreated the prognosis of live born infants with tricuspid 8. Rao PS. Demographic features of tricuspid atresia. In: Rao PS
atresia is poor; only 10 to 20 percent may survive their first (Ed). Tricuspid Atresia, 2nd edition, Mount Kisco, NY, Futura
birthday.9,119 Palliative surgery to normalize the pulmonary Publishing Co. 1992.p.23.
blood flow has markedly improved the survival rate. But, as 9. Dick M, Fyler DC, Nadas AS. Tricuspid atresia: clinical course
one can see from survival data from several large studies,51,120 in 101 patients. Am J Cardiol. 1975;36:327.
there is still considerable early mortality. Because of recent 10. Van Praagh R, Ando M, Dungan WT. Anatomic types of
improvement in surgical mortality for the palliative surgery and tricuspid atresia: clinical and developmental implications
(abstract). Circulation. 1971;44:115.
advances in neonatal care, the initial mortality should decrease.
11. Astley R, Oldham JS, Parson C. Congenital tricuspid atresia. Br
Introduction of physiologically ‘corrective’ surgery in the Heart J. 1953;15:287.
early 1970s has, to some degree, improved the second bout of 12. Kühne M. Über zwei falle kongenitaler atreside des ostium
mortality seen in children beyond 15 years of age. Because of venosum dextrum. Jahrb Kinderh. 1906;63:235.
this improved prognosis, each neonate with tricuspid atresia 13. Edwards JE, Burchell HB. Congenital tricuspid atresia: a
should be offered aggressive medical and surgical therapy.121 classification. Med Clin North Am. 1949;33:1117.
14. Keith JD, Rowe RD, Vlad P. Tricuspid atresia. In: Heart Disease
in Infancy and Childhood, New York: Macmillian. 1958.p.434.
CONCLUSION
15. Rao PS. Classification of tricuspid atresia. In: Rao PS (Ed).
Tricuspid Atresia, 2nd edition, Mount Kisco, NY, Futura
Tricuspid atresia is the third most common cyanotic
Publishing Co. 1992.p.59.
congenital heart defect. There are significant variations in 16. Van Praagh R. Discussion after paper by Vlad P: Pulmonary
the morphology of the atretic tricuspid valve, the associated atresia with intact ventricular septum. In: Barrett-Boyes BG,
cardiac defects and physiology, resulting in different clinical Neutze JM, Harris EA (Eds). Heart Disease in Infancy: Diagnosis
presentations. The diagnosis is relatively simple and can often and Surgical Treatment, London: Churchill Livingstone,
be made on clinical features and simple laboratory studies 1973.p.236.
(chest roentgenogram and electrocardiogram), which can be 17. Rao PS. Tricuspid atresia: anatomy, imaging, and natural history.
confirmed by echocardiography and if necessary by cardiac In: Freedom RM (Ed). Congenital Heart Disease. In: Braunwald
catheterization and selective cineangiography. Aggressive E (Ed): Atlas of Heart Diseases: Philadelphia, Current Medicine.
1997;12:141.
management to normalize the pulmonary blood flow and
18. Keith JD, Rowe RD, Vlad P. Tricuspid atresia, In: Heart Disease
correct physiologically important associated defects (e.g. in Infancy and Childhood, 2nd edition, New York: Macmillian,
coarctation of the aorta) should be undertaken at the time of 1966.p.664.
presentation. Follow-up and treatment plans should strive 19. Vlad P. Tricuspid atresia. In: Keith JD, Rowe RD, Vlad P (Eds).
to maintain or normalize cardiac structures and function Heart Disease in Infancy and Childhood, 3rd edition, New York:
(pulmonary artery anatomy and pressure and left ventricular Macmillian. 1977.p.518.
function). Finally, performing staged Fontan-Kreutzer surgery 20. Rao PS. Classification of tricuspid atresia. In: Rao PS (Ed).
prior to deterioration of the left ventricular function should Tricuspid Atresia, Mount Kisco, NY, Futura Publishing Co.
markedly improve the prognosis for tricuspid atresia patients. 1982.p.41.
21. Van Praagh R. Terminology of congenital heart disease: glossary
and commentary. Circulation. 1977;56:139.
He is the best physician who is the most ingenious inspirer 22. Weinberg PM. Pathologic anatomy of tricuspid atresia. In: Rao
of hope. PS (Ed). Tricuspid Atresia, Mount Kisco, NY, Futura Publishing
—Samuel Taylor Coleridge Co. 1982.p.49.
23. Rao PS, Levy JM, Nikiciz E, et al. Tricuspid atresia: association
REFERENCES with persistent truncus arteriosus. Am Heart J. 1991;122:829.
24. Bharati S, McAllister HA Jr, et al. Anatomic variations in
1. Rao PS. A unified classification for tricuspid atresia. Am Heart J. underdeveloped right ventricle related to tricuspid atresia and
1980;99:799. stenosis. J Thorac Cardiovasc Surg. 1976;72:383.
2. Rao PS. Terminology: tricuspid atresia or univentricular heart? 25. Ando M, Santomi G, Takao A. Atresia of tricuspid and mitral
In: Rao PS (Ed). Tricuspid Atresia, Mount Kisco, NY, Futura orifice: anatomic spectrum and morphogenetic hypothesis. In:
Publishing Co, 1982.p.3. Van Praagh R, Takao A (Eds). Etiology and Morphogenesis of
3. Rao PS. Is the term “tricuspid atresia” appropriate? (Editorial). Congenital Heart Disease, Mount Kisco, NY, Futura Publishing
410
Am J Cardiol. 1990;6:1251. Co. 1980.p.421.
26. Anderson RH, Wilkinson JL, Gerlis LM, et al. Atresia of the 45. Marcano BA, Riemenschnieder TA, Ruttenburg HD, et al. 28
right atrioventricular orifice. Br Heart J. 1977;39:414. Tricuspid atresia with increased pulmonary blood flow: an
27. Weinberg PM. Anatomy of tricuspid atresia and its relevance to analysis of 13 cases. Circulation. 1965;40:399.
Tricuspid Atresia
current forms of surgical therapy. Ann Thorac Surg. 1980;29: 46. Rao PS. Cardiac catheterization in tricuspid atresia. In: Rao PS
306. (Ed). Tricuspid Atresia, Mount Kisco, NY, Futura Publishing
28. Rao PS, Jue KL, Isabel-Jones J, et al. Ebstein’s malformation Co. 1982.p.153.
of the tricuspid valve with atresia: differentiation from isolated 47. LaCorte MA, Dick M, Scheer G, et al. Left ventricular function
tricuspid atresia. Am J Cardiol. 1973;32:1004. in tricuspid atresia. Circulation. 1975;52:996.
29. Rao PS. Atrioventricular canal mimicking tricuspid atresia: 48. Graham TP, Erath HJG, Boucek RJ, et al. Left ventricular
echocardiographic and angiographic features. Br Heart J. function in cyanotic congenital heart disease. Am J Cardiol.
1987;58:409. 1980;45:1231.
30. Scalia D, Russo P, Anderson RH, et al. The surgical anatomy of 49. Rao PS, Alpert BS, Covitz W. Left ventricular function in
the heart with no direct communication between the right atrium tricuspid atresia. In: Rao PS (Ed). Tricuspid Atresia, 2nd edition.
and the ventricular mass so called tricuspid atresia. J Thorac Mount Kisco, NY, Futura Publishing Co. 1992.p.247.
Cardiovasc Surg. 1984;87:743. 50. Rao PS. Left-to-right shunting in tricuspid atresia. Br Heart J.
31. Rao PS, Sissman NJ. Spontaneous closure of physiologically 1983;49:345.
advantageous ventricular septal defects. Circulation. 1971;43:83. 51. Dick M, Rosenthal A. The clinical profile of tricuspid atresia.
32. Rao PS, Linde LM, Liebman J, et al. Functional closure of In: Rao PS (Ed). Tricuspid Atresia, Mount Kisco, NY, Futura
physiologically advantageous ventricular septal defects: Publishing Co. 1982.p.83.
observations in three cases with tricuspid atresia. Am J Dis 52. Taussig HB. The clinical and pathologic findings in congenital
Child. 1974;127:36. malformations of the heart due to defective development of the
33. Rao PS. Natural history of the ventricular septal defect in right ventricle associated with tricuspid atresia or hypoplasia.
tricuspid atresia and its surgical implications. Br Heart J. Bull Hopkins Hosp. 1936;59:435.
1977;39:276. 53. Wittenborg MH, Neuhauser EBD, Sprunt WH. Roentgenographic
34. Rao PS. Further observations on the spontaneous closure findings of congenital tricuspid atresia with hypoplasia of the
of physiologically advantageous ventricular septal defects right ventricle. Am J Roentgenol. 1951;64:712.
in tricuspid atresia: surgical implications. Ann Thorac Surg. 54. Elster SK. Congenital atresia of pulmonary and tricuspid valves.
1983;35:121. Am J Dis Child. 1950;79:692.
35. Gallaher ME, Fyler DC. Observations on the changing 55. Covitz W, Rao PS. Noninvasive evaluation of patients with
hemodynamics in tricuspid atresia without transposition of the tricuspid atresia (Roentgenography, echocardiography and
great vessels. Circulation. 1967;35:381. nuclear angiography). In: Rao PS (Ed). Tricuspid Atresia, 2nd
36. Sauer U, Hall D. Spontaneous closure or critical decrease in edition, Mount Kisco, NY, Futura Publishing Co. 1992.p.165.
size of the ventricular septal defect in tricuspid atresia with 56. Gamboa R, Gersony WM, Nadas AS. The electrocardiogram in
normally connected great arteries: surgical implications. Herz. tricuspid atresia and pulmonary atresia with intact ventricular
1980;5:369. septum. Circulation. 1986;34:24.
37. Rao PS. Physiologically advantageous ventricular septal defects 57. Patel R, Fox K, Taylor JFN, et al. Tricuspid atresia—clinical
(Letter). Pediat Cardiol. 1983;4:59. course in 62 cases (1967-1974). Br Heart J. 1978;40:1408.
38. Rao PS. Natural history of ventricular septal defects in tricuspid 58. Rao PS, Kulungara RJ, Boineau JP, et al. Electrovector
atresia. In: Rao PS (Ed). Tricuspid Atresia, 2nd edition, Mount cardiographic features of tricuspid atresia. In Rao PS (Ed).
Kisco, NY, Futura Publishing Co. 1992.p.261. Tricuspid Atresia, 2nd edition. Mount Kisco, NY, Futura
39. Rao PS. Subaortic obstruction after pulmonary artery banding Publishing Co. 1992.p.141.
in patients with tricuspid atresia and double-inlet left ventricle 59. Puri PS, Neill CA. Vectorcardiographic study in ten cases of
and ventriculoarterial discordance (Letter). J Am Coll Cardiol. tricuspid atresia. In: Cassels DE, Ziegler RF (Ed). Electrocardio
1991;66:406. graphy in Infants and Children, New York: Grune and Stratton.
40. Bharati S, Lev M. The concept of tricuspid atresia complex as 1966.p.269.
distinct from that of the single ventricle complex. Pediat Cardiol. 60. Bharati S, Lev M. Conduction system in tricuspid atresia with
1979;1:57. and without regular (d) transposition. Circulation. 1977;56:423-
41. Rosenthal A, Dick M II. Tricuspid atresia. In: Adams FH, 29.
Emmanouilides GC (Eds). Moss Heart Disease in Infants, 61. Dickenson DF, Wilkinson JL, Smith A, et al. Atrioventricular
Children and Adolescents. 3rd edition, Baltimore, Williams and conduction tissues in univentricular hearts of left ventricular
Wilkins. 1983.p.271. type with absent right atrioventricular connection (“tricuspid
42. Rao PS, Covitz W, Chopra PS. Principles of palliative atresia”). Br Heart J. 1979;42:1.
management of patients with tricuspid atresia. In: Rao PS 62. Guller B, Dushane JW, Titus JL. Atrioventricular conduction
(Ed). Tricuspid atresia, 2nd edition, Mount Kisco, NY, Futura system in two cases of tricuspid atresia. Circulation. 1969;40:217.
Publishing Co. 1992.p.297. 63. Kulungara RJ, Boineau JP, Moore HV, et al. Ventricular
43. Rudolph AM. Tricuspid atresia with hypoplastic right ventricle. activation and genesis of QRS in tricuspid atresia (abstract).
In: Congenital Disease of the Heart, Chicago Year Book Medical Circulation. 1981;64:IV-225.
Publishers. 1974.p.429. 64. Seward JB, Tajik AJ, Hagler DJ, et al. Echocardiographic
44. Rao PS. Perinatal Circulatory Physiology: It’s influence spectrum of tricuspid atresia. Mayo Clin Proc. 1978;53:100.
411
on clinical manifestations of neonatal heart disease – Part I. 65. Silverman NH, Payot M, Stanger P. Simulated tricuspid valve
Neonatology Today. 2008;3:6-12. echoes in tricuspid atresia. Am Heart J. 1978;95:761.
http://vip.persianss.ir
6 66. Beppu S, Nimura Y, Tamai M, et al. Two-dimensional echo
cardiography in the diagnosis of tricuspid atresia: differentiation
86. Gibbs JL, Rothman MT, Rees MR, et al. Stenting of arterial
duct: a new approach to palliation of pulmonary atresia. Br
from other hypoplastic right heart syndromes and common Heart J. 1992;67:240.
Congenital Valvar Lesions
atrioventricular canal. Br Heart J. 1978;40:1174. 87. Siblini G, Rao PS, Singh GK, et al. Transcatheter management
67. Rao PS. Pathophysiologic consequences of cyanotic heart of neonates with pulmonary atresia and intact ventricular
disease. Indian J Pediat. 1983;50:479-87. septum. Cathet Cardiovasc Diagn. 1997;42:395.
68. Mair DD, Hagler DJ, Puga FJ, et al. Fontan operation in 176 88. McCredie RM, Lee CL, Swinburn MJ, et al. Balloon dilatation
patients with tricuspid atresia: results and a proposed new index pulmonary valvuloplasty in pulmonary stenosis Aust New
for patient selection. Circulation. 1990;82(Supp IV).164. Zealand J; Med. 1986;16:20.
69. Campbell M, Hills TH. Angiocardiography in cyanotic 89. Peck GJ, Arsiwala SS, Chan C, et al. Absorbable pulmonary
congenital heart disease. Br Heart J. 1950;12:65. artery band. Ann Thorac Surg. 1997;64:539.
70. Cooley RN, Sload RD, Hanlon CR, et al. Angiocardiography 90. Bonnet D, Sidi D, Vouhé PR. Absorbable pulmonary artery
of cyanotic type II. Observations as tricuspid stenosis or atresia banding in tricuspid atresia. Ann Thorac Surg. 2001;71:360.
with hypoplasia of the right ventricle. Radiol. 1950;54:848. 91. Rao PS. Absorbable pulmonary artery band in tricuspid atresia
71. Schwartz DC, Rao PS. Angiography in tricuspid atresia. In: (Editorial). Ann Thorac Surg. 2001;71:361.
Rao PS (Ed). Tricuspid Atresia, 2nd edition, Mount Kisco, NY, 92. Rashkind WJ, Waldhausen JA, Miller WW, et al. Palliative
Futura Publishing Co. 1992.p.223. treatment of tricuspid atresia: combined balloon atrial
72. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. septostomy and surgical alteration of pulmonary blood flow. J
1971;26:240. Thorac Cardiovasc Surg. 1969;57:812.
73. Kreutzer G, Bono H, Galindez E, et al. Una operacion para la 93. Rao PS. Role of Interventional Cardiology. In: Neonates: Part
correccion de la atresia tricuspidea. Ninth Argentinean Congress I. Non-Surgical Atrial Septostomy. Congenital Cardiol Today.
of Cardiology, Buenos Aires, Argentina, Oct. 31-Nov. 6, 1971. 2007;5:1-12.
74. DeLaval MR, Kilner P, Gewilling M, et al. Total cavopulmonary 94. Park SC, Neches WH, Zuberbuhler JR, et al. Clinical use of
connection: a logical alternative to atriopulmonary connection blade atrial septostomy. Circulation. 1978;58:600.
for complex Fontan operation. J Thorac Cardiovasc Surg. 95. Rao PS. Transcatheter blade atrial septostomy. Cathet Cardiovasc
1988; 96:682. Diagn. 1984;10:335.
75. Chopra PS, Rao PS. Corrective surgery for tricuspid atresia: 96. Salim M, Muster AJ, Paul MH, et al. Relation between
which modifications of Fontan-Kreutzer procedure should be preoperative left ventricular muscle mass and outcome of the
used? A review. Am Heart J. 1992;123:758. Fontan procedure in patients with tricuspid atresia. J Am Coll
76. Rao PS, Chopra PS. Modification of Fontan-Kreutzer procedure Cardiol. 1989;14:750-55.
for tricuspid atresia: can a choice be made? In: Rao PS (Ed). 97. Ottenkamp J, Wenink ACG, Quaegebeur JM, et al. Tricuspid
Tricuspid Atresia, 2nd edition, Mount Kisco, NY, Futura atresia: Morphology of the outlet chamber with special
Publishing Co. 1992.p.361. emphasis on surgical implications. J Thorac Cardiovasc Surg.
77. Rao PS. Principles of management of the neonate with 1985;89:597-603.
congenital heart disease. Neonatology Today. 2007;2:1-10. 98. Smolinsky A, Castaneda AR, Van Praagh R. Infundibular
78. Freed MD, Heymann MA, Lewis AB, et al. Prostaglandin E1 septal resection: Surgical anatomy of the superior approach. J
in the infants with ductus arteriosus dependent congenital heart Thorac Cardiovasc Surg. 1988;95:486-94.
disease: The US experience. Circulation. 1981;64:899. 99. Hopkins RA, Armstrong SSE, Serwer GA, et al. Physiologic
79. Rao PS. Congenital Heart Disease. In: Rakel RE (Ed). Conn’s rationale for a bidirectional cavopulmonary shunt: a versatile
Current Therapy, Philadelphia, In: PA, WB Saunders, (Eds). complement to the Fontan principle. J Thorac Cardiovasc Surg.
1989.p.201. 1985;90:391.
80. Rao PS, Thapar MK, Galal O, et al. Follow-up results of balloon 100. Marcelletti C, Corno A, Giannico S, et al. Inferior vena cava-
angioplasty of native coarctation in neonates and infants. Am pulmonary artery extracardiac conduit. A new form of right
Heart J. 1990;120:1310. heart bypass. J Thorac Cardiovasc Surg. 1990;100:313-14.
81. Rao PS, Galal O, Smith PA, et al. Five to nine year follow-up 101. Pridjian AK, Mendelsohn AM, Lupinetti FM, et al. Usefulness
results of balloon angioplasty of native aortic coarctation in of the bidirectional Glenn procedure as staged reconstruction
infants and children. J Am Coll Cardiol. 1996;27:462-70. for the functional single ventricle. Am J Cardiol. 1993;71:959-
82. Rao PS. Current status of balloon angioplasty for neonatal and 62.
infant aortic coarctation. Progress Pediat Cardiol. 2001;14:35- 102. Tanoue Y, Sese A, Ueno Y, et al. Bidirectional Glenn procedure
44. improves the mechanical efficiency of a total cavopulmonary
83. Blalock A, Taussig HB. The surgical treatment of malformations connection in high-risk fontan candidates. Circulation.
of the heart in which there is pulmonary stenosis or pulmonary 2001;103:2176-80.
atresia. J Am Med Assoc. 1945;128:189. 103. Billingsley AM, Laks H, Boyce SM, et al. Definitive repair in
84. DeLeval M, McKay R, Jones M, et al. Modified Blalock-Taussig some patients with pulmonary atresia with intact ventricular
shunt: use of subclavian orifice as a flow regulator in prosthetic septum. J Thorac Cardiovasc Surg. 1989;97:746-54.
systemic-pulmonary artery shunts. J Thorac Cardovasc Surg. 104. Bridges ND, Lock JE, Castaneda AR. Baffle fenestration
1981;18:112. with subsequent transcatheter closure: modification of the
85. Annecchino FP, Fontan F, Chauve A, et al. An operation for the Fontan operation for patients with increased risk. Circulation.
correction of tricuspid atresia. Ann Thorac Surg. 1979;29:317. 1990;82:1681.
412
105. Laks H, Pearl JM, Haas GS, et al. Partial Fontan advantages trophysiologic benefit of early atrioventricular resynchroniza- 28
of an adjustable interatrial communication. Ann Thorac Surg. tion. Texas Heart Institut. 2007;34:96-101.
1991;52:1084. 114. Estner HL, Kolb C, Schmitt C, et al. Long-term transvenous
Tricuspid Atresia
106. Choussat A, Fontan F, Besse P, et al. Selection criteria for Fontan AV-sequential pacing in a failing atriopulmonary Fontan
procedure. In: Anderson RH, Shinebourne EA (Eds). Paediatric patient. Int J Cardiol. 2008;127:e93-95.
Cardiology, Edinburgh, Churchill Livingstone. 1978.p.559. 115. Marcelletti CF, Hanley FL, Mavroudis C, et al. Revision of
107. Freedom RM, Gow R, Caspi J, et al. The Fontan procedure for previous Fontan connections to total extracardiac cavopulmo-
patients with tricuspid atresia: Long-term follow-up. In: Rao nary anastomosis: A multicenter experience. J Thorac Cardio-
PS (Ed). Tricuspid Atresia, 2nd edition. Futura Publishing Co, vasc Surg. 2000;119:340-46.
Mount Kisco, NY. 1992. pp.377-86. 116. Sheikh AM, Tang AT, Roman K, et al. The failing Fontan circu-
108. Gandhi SK, Bromberg BI, Schuessler RB, et al. Characterization lation: successful conversion of atriopulmonary connections. J
and surgical ablation of atrial flutter after classic Fontan repair Thorac Cardiovasc Surg. 2004;128:60-66.
in acute canine model. Ann Thorac Surg. 1996;61:1666-78. 117. Gamba A, Merlo M, Fiocchi R, et al. Heart transplantation in
109. Rao PS, Chandar JS, Sideris EB. Role of inverted buttoned patients with previous Fontan operations. J Thorac Cardiovasc
device in transcatheter occlusion of atrial septal defect or Surg. 2004;127:555-62.
patent foramen ovale with right-to-left shunting associated 118. Jayakumar KA, Addonizio LJ, Kichuk-Chrisant MR, et al. Car-
with complex congenital cardiac anomalies. Am J Cardiol. diac transplantation after the Fontan or Glenn procedure. J Am
1997;80:914-21. Coll Cardiol. 2004;44:2065-72.
110. Goff DA, Blume ED, Gauvreau K, et al. Clinical outcome 119. Rowe RD, Freedom RM, Mehrizi A, et al. The Neonate
of fenestrated Fontan patients after closure: the first 10 with Congenital Heart Disease. Major Problems in Clinical
years. Circulation. 2000;102:2094-99. Pediatrics. 2nd edition, Vol 5, Philadelphia: WB Saunders Co.
111. Hill DJ, Feldt RH, Porter C, et al. Protein losing enteropathy 1981.p.456.
after Fontan operation: A preliminary report (Abstract). 120. Franklin RCG, Spregethalter DJ, Sullivan ID, et al. Tricuspid
Circulation. 1989;80:490. atresia presenting in infancy: survival and suitability for the
112. Rao PS. Protein-losing enteropathy following the Fontan Fontan operation. Circulation. 1993;87:427.
operation (Editorial). J Invasive Cardiol. 2007;19:447-48. 121. Rao PS. Tricuspid Atresia. In: Pediatric Cardiovascular Medi-
113. Lopez JA. Transvenous right atrial and left ventricular pacing cine. Moller JH, Hoffman JIE (Eds). Churchill Livingstone,
after the Fontan operation: long-term hemodynamic and elec- New York, NY. 2000.pp.421-41.
413
http://vip.persianss.ir
C hapter
http://vip.persianss.ir
6 inadequate RV myocardium to generate high enough pressure PFO. This leads to severe cyanosis and severe metabolic
to achieve forward flow via the pulmonary valve. This is acidosis in the newborn.
compounded by high pulmonary vascular resistance and PDA Cyanosis is noted in approximately 50 percent of the
congenital ValVular lesions
leading to inability of the pulmonary valve leaflets to open. newborn.3,31 In infants beyond the neonatal period, cyanosis is
This leads to ‘functional’ pulmonary atresia. In such patients, also a common presentation. Murmur and heart failure features
pulmonary valve may open after the pulmonary vascular are less common presenting features. Incidental finding of
resistance decreases either as natural course or by medical cardiomegaly in a chest X-ray performed for another purpose
treatment. is another mode of presentation. Supraventricular tachycardia
Right to left shunting at atrial septal level, leading to may also be a presenting feature.
cyanosis in the newborn, may resolve as the pulmonary
vascular resistance (PVR) decreases along with establishment Children, Adolescents and Adults
of forward flow via the pulmonary valve. Degree to which
such resolution occurs depends on the severity of the defect. They are largely asymptomatic and may be detected by a
Cyanosis may return in later childhood or adolescence when cardiac murmur or by echocardiogram performed for an
tricuspid valve function deteriorates (causing regurgitation). unrelated problem. Infants with moderate to severe forms,
This clinical course is described in the old literature as who improved after normalization of pulmonary pressures,
‘transient’ or ‘intermittent’ cyanosis. may become symptomatic as the tricuspid valve and right
ventricular function deteriorates. Easy fatigability, cyanosis
Clinical Presentation or arrhythmia may be presenting symptoms.
Celermajer et al32 reviewed 220 cases with Ebstein anomaly
Wide spectrum of pathophysiology, as noted above, allows for and found that most common presenting symptom varied with
differing presentations, which are dependent upon severity of age—prenatal scans for fetuses is 86 percent, cyanosis for
each component of lesion and associated lesions. Mild cases neonates is 74 percent, heart failure for infants is 43 percent,
may not be detected until adulthood. Mildest cases are detected incidental murmur for children is 63 percent and arrhythmia
serendipitously during an echocardiogram performed for an for adolescents and adults is 42 percent. Early presentations
unrelated reason. Most severe forms present during neonatal were associated with RV outflow tract obstruction.
period. Flores Arizmendi and associates33 followed 52 patients
from the time of diagnosis (ranging from fetal life to
Fetus adulthood) to a mean of 16.7 years. 24 patients presented
during newborn period and eleven (46%) of these patients
In fetus, Ebstein anomaly may present as cardiomegaly, died. Actuarial survival for the entire group at 30 years was
tricuspid regurgitation, with right atrial enlargement on fetal 65 percent. Twenty-seven (66%) of the 41 survivors had
echocardiography, arrhythmia or heart failure with hydrops. arrhythmias and 25 of the 27 were receiving medications for
Fetal presentation is associated with high incidence of fetal arrhythmia. Nine patients have had surgery. Celermajer index
loss.30 of three or four (See under Fetal and Neonatal Diagnosis
section) and CT ratio more than 65 percent were found to be
Neonates and Infants predictive of death.33
a B
figures 1a and B: Panel A. Chest X-ray of a newborn with severe Ebstein anomaly of the tricuspid valve showing severe cardiomegaly, typical 417
for this lesion with right atrial enlargement, representing most of the enlargement of cardiac silhouette; Panel B. Chest X-ray of a 4-year-old child
with milder form of Ebstein anomaly
http://vip.persianss.ir
6
congenital ValVular lesions
figure 2: Electrocardiogram of a newborn with Ebstein anomaly. Note the tall P waves representing right atrial enlargement
frequency (30%) in Ebstein anomaly while a few (12%) have are easy to detect. However, diagnosis of mild Ebstein
evidence of pre-excitation with normal PR interval.40 anomaly may be debatable since normal TV is displaced
slightly when compared with crux of the heart or mitral
Echocardiography valve annulus. In a study of 41 patients seen at Mayo clinic
(Minnesota) with mean age of 18 years, a displacement of
The diagnosis is established by echocardiographic studies greater than or equal to 8 mm/m2 of body surface area
and they provide necessary information for assessment of was established as a criterion to judge the displacement.41
severity and prognosis. Technological advances have made However, in the opinion of the authors of this chapter,
echocardiography the main modality of diagnosis for Ebstein this criterion alone will over-diagnose Ebstein anomaly
anomaly. Morphologic correlates of Ebstein anomaly have in the newborn whose usual body surface area is around
been well described in literature41-44 and well-reviewed in 0.20 m2. TV displacement of 1.5–2 mm below the mitral
textbooks.45 valve annulus or crux of the heart is not unusual in a
Objectives of echocardiography are to evaluate the degree normal newborn. Presence of other features should also
of dysplasia and displacement of tricuspid valve leaflets be taken into account in this diagnosis rather than isolated
from the true annulus (which in turn influence the degree of displacement of septal leaflets.
tricuspid valve regurgitation), RV size and RV function. 2. Dysplasia or absence of septal leaflet. Septal leaflet may
be dysplastic and/or fibrotic or absent. When the leaflet is
Evaluation of Tricuspid Valve and its Attachments absent, it may be represented by remnants of tissue seen at
the mid-portion of the ventricular septum.
1. Degree of inferior displacement of the tricuspid valve 3. Subvalvar apparatus. Short chordae may attach the septal
(TV) leaflets. The hinge points of the septal and posterior leaflet to the ventricular septum. Sometimes, the chordae
leaflets are usually displaced downward towards the may be absent with insertion of the leaflet directly to the
apex. Anterior leaflet usually is not displaced. Apical four ventricular septum in apical four chamber view.
chamber view (Figures 3A and B) is the best to estimate the 4. Anterior leaflet can be visualized in either apical four
displacement. Mitral valve annulus serves as a reference chamber view or parasternal long axis view aimed towards
to quantitate the degree of displacement. Severity of the right ventricular inflow. Anterior leaflet is usually
Ebstein anomaly varies with the degree of displacement very large with ‘sail-like’ mobility consisting of bulging
of the septal leaflet. Moderate to severe displacements into RVOT during diastole and folding during systole.46
418
29
http://vip.persianss.ir
6 RV volume overload with paradoxical septal movement 2. Certain degree of RV dysplasia may be present. This is
is also seen. Apical four chamber view helps to measure considered to exist if RV wall thickness is less than two
the sizes of the RA, atrialized RV and the functional distal standard deviation (SD), size of RV is more than two SD or
congenital ValVular lesions
chamber of RV. Ratio of area of RA plus atrialized RV to there is dyskinesia of atrialized or the functional portion of
the combined area of functional, distal portion of RV, LV RV.43 Even though, the atrialized portion of RV bulges into
and LA (Figure 5) has been used as a prognostic factor to the LV outflow tract (Figures 6A and B), obstruction to LV
predict survival in newborn with Ebstein anomaly.47 (See outflow tract rarely occurs to a clinically significant degree.
under Fetal and Neonatal Diagnosis section below). 3. RV outflow tract obstruction may occur secondary to:
i. Attachment of anterior leaflet.
ii. Functional pulmonary valve atresia.
iii. True anatomic pulmonary valve atresia.
In a newborn, it may be extremely difficult to differentiate
functional from true pulmonary valve atresia. Functional
pulmonary atresia is said to exist if the pulmonary valve
leaflets are normally formed (not fused), but are unable
to open due to inability of the functional RV to generate
enough systolic pressure against the relatively elevated
pulmonary artery pressure. Pulmonary artery pressure in
a newborn may be elevated due to the normally elevated
neonatal pulmonary vascular resistance or due to presence
of a large PDA either naturally or from of prostaglandin
infusion (see Medical management section below).
Presence of any pulmonary regurgitation by color Doppler
imaging favors a functional pulmonary atresia. Ability to
pass a catheter across pulmonary valve should the baby
undergo a cardiac catheterization as newborn may help to
differentiate. However, inability to pass a catheter does not
always mean an anatomic pulmonary atresia. Occasionally,
only way to differentiate may be to wait until pulmonary
figure 5: Apical four-chamber view showing all chambers of the heart
in end-diastole. Tracing on the image shows the two areas used to
vascular resistance drops as the newborn transitions from
obtain the ratio (Celermajer index) for prediction of outcome in fetal and fetal circulation to postnatal circulation. There are reports
neonatal echocardiograms (see text for further details). Abbreviations of inhaled nitric oxide therapy helping to differentiate this
are same as those used in Figure 3 as well.48
a B
420
figures 6a and B: Apical five-chamber view of echocardiogram showing two-dimensional frame. A. With color Doppler; B. Showing the bulging
of the right ventricle (RV) into left ventricular outflow tract (LVOT). In this example, there is no significant obstruction; note laminar flow in the
LVOT and aorta (Ao). LA = Left atrium; LV = Left ventricle; RA = Right atrium
Three-dimensional Echocardiography performed, right to left shunting at atrial level may be present 29
by oximetry. Left to right shunting is unusual unless there
Newer technology with three-dimensional imaging (transtho- is VSD or PDA. Pressure traces have some characteristic
a B
figures 7a and B: A. Right ventricular angiogram in posteroanterior view from an adolescent with Ebstein anomaly. Contrast was injected via 421
the venous catheter (C) in right ventricle (RV). Tricuspid valve regurgitation leads to opacification of an enlarged right atrium (RA). The true
tricuspid valve annulus (arrow) and attachment of the displaced tricuspid valve leaflets (arrows) are shown; B. In a subsequent cine frame,
atrialized RV (a RV) is shown. MPA = Main pulmonary artery
http://vip.persianss.ir
6
congenital ValVular lesions
anomaly or TV dysplasia diagnosed between 1984–2010 LV compression by RV dilatation and Celermajer index
were reviewed.56 Twenty-six had Ebstein anomaly and eleven exceeding one.43, 57
had TV dysplasia. There were pregnancy terminations in
ten, intrauterine deaths in five and neonatal deaths in eight. Differential Diagnosis
Fourteen fetuses survived. Presence of retrograde flow across
the pulmonary valve in the first fetal echocardiogram was Severe cardiomegaly with pulmonary oligemia in a cyanotic
a strong predictor of fetal or neonatal death. Presence of newborn is highly suggestive of Ebstein anomaly; however,
antegrade flow through pulmonary valve was associated with the following conditions should also be considered in
good prognosis. Celermajer index did not predict outcome in such situations—Critical PS or pulmonary atresia with
this cohort adequately while the more extensive SAS predicted intact ventricular septum and ‘functional’ pulmonary
outcome adequately.56 atresia. Tricuspid atresia, TGA and TOF may rarely mimic
A recent single-center study from Boston Children’s Ebstein anomaly. But, their clinical features are distinctive.
Hospital reviewed 66 patients diagnosed between 1984 and Echocardiography will differentiate these conditions from
2004.57 Sixty-one of them were Ebstein anomaly and five were Ebstein anomaly.
TV dysplasia. Thirty-three were diagnosed prenatally, while It is of considerable concern when these patients are
33 were diagnosed after birth. Median follow-up duration referred for surgery in that there is a potential for error in
was 6.3 years. Of the 33 fetal diagnoses, 8 (24%) underwent the diagnosis of Ebstein anomaly when one is faced with a
medical termination, 9 (27%) died in utero and 16 were born tricuspid valve disease with significant tricuspid regurgitation.
alive. Nine of these 16 (56%) died in neonatal period. Overall, In a study of cases referred, diagnosed as Ebstein anomaly
7 of 33 fetal diagnosis patients survived beyond 1 month of for surgical repair between 1982 and 1995, 22 patients
age. Factors associated with poor outcome were moderate or were identified in whom the diagnosis was changed. All 22
severe tricuspid regurgitation, Celermajer index more than patients had prominent RA and RV enlargement. However,
1.0 and absence of forward flow through pulmonary valve. Of Ebstein anomaly was ruled out in these patients prior to
the 49 newborn babies, 29 percent died in the hospital and 35 surgery using two important echocardiographic parameters
were discharged home. Even though mortality was lower for namely:
the cohort diagnosed after 1997 (29% vs 54%), mortality still i. Significant apical displacement of septal leaflet of
remains high for the most severe group. Therefore, strategies tricuspid valve (≥ 8 mm/m2).
different from what are being used currently will be needed ii. Redundant, elongated anterior leaflet of the tricuspid
such as steroids in the third trimester to help lung maturity, valve.
delivery in middle of third trimester, early institution of Fifteen of these 22 patients underwent surgery and
ventilation and management of metabolic derangement after Ebstein anomaly was ruled out by surgical anatomy
birth to help avoid burden from poorly expanded/poorly as well. Alternative diagnoses established in these
formed lungs, etc.57 When the presentation is in the neonatal patients included TV dysplasia (n = 9), TV prolapse (n
period, severe RV outflow tract obstruction is also a risk factor = 4), trauma (n = 4), RV dysplasia (n = 3), endocarditis
for mortality.43,57 (n = 1) and annular dilatation secondary to free pulmonary
In summary, when the presentation is in fetal and regurgitation (n = 1). Absence of the two characteristic
newborn periods, the following are associated with death echocardiographic signs of Ebstein anomaly, mentioned
by 3 months of age—severe RV outflow tract obstruction, above should raise possibilities of other types of tricuspid
tethered distal attachment of anterior leaflet, RV dysplasia, valve diseases. 58 423
http://vip.persianss.ir
6 Natural History may relieve systemic venous congestion, one should be aware
Several studies38,59-62 examining natural history will be of the increase in cyanosis that may occur due to increased
reviewed in order to get a sense of how the patients do right to left shunting at the atrial level after septostomy.
congenital ValVular lesions
over time. An early study from Boston Children’s Hospital Right ventricular outflow tract obstruction is commonly
reviewed the outcome of Ebstein anomaly;38 isolated Ebstein secondary to anterior leaflet attachments. Therefore, balloon
anomaly—70 percent survived up to 2 yrs and 50 percent pulmonary valvuloplasty is unlikely to help unless valvar
survived up to 13 yrs. Ebstein anomaly patients with associated stenosis is a significant part of RV outflow tract obstruction.
anomalies, however had a 15 percent survival at 2 years.59 In
another study of 505 patients,59 minimal disability was present Surgical Management
in 73 percent of 1 to 15 year-old, 69 percent of 16 to 25 year
age group and 59 percent of subjects above 25 years of age. Multiple surgical approaches have been described for
Therefore, early diagnosis alone should not be an indication treatment of Ebstein anomaly and will be reviewed briefly.
for surgery.60 Carpentier type A and B14 babies are likely to Simple closure of ASD: Surgical closure of PFO/ASD
recover with medical management in the neonatal period.61 may provide symptomatic improvement by controlling a
A recent study from Belgium62 documents outcome in a significant left to right shunting and mild cyanosis (secondary
cohort of 49 patients who were more than 16 years old. Mean to right to left shunting) at baseline or with exercise. This may
follow-up period was 11.4 years (1–32 year). Half of them be useful in a small number of individuals. In such patients,
(51%) has undergone tricuspid valve surgery; surgical repair transcatheter closure of ASD63 may be considered after a test-
of the valve (valvuloplasty) in 16 and valve replacements in occlusion to prove that the cardiac output does not decrease
nine. Eight patients required reoperation to repeat tricuspid and right atrial pressure does not unduly increase. For most of
valve repair. Twenty-six (51%) patients had SVT. Typical the other patients, tricuspid valve (Ebstein anomaly) should
WPW syndrome was noted in 15 (31%) and ablation was be addressed surgically.
performed in 17 (34%). Pacemaker was implanted in 5 Repair or replacement of tricuspid valve: Danielson et
(10%).62 al64 performed repair of tricuspid valve and closed the ASD
(Figures 11A and B). Repair of TV consisted of plication
Management of atrialized portion of RV, narrowing the size of tricuspid
valve and creating a monoleaflet tricuspid valve that is
competent.64,65 Supravalvar positioning of the prosthetic
Medical Management
tricuspid valve decreased the incidence of AV block following
The management depends on severity and age at presentation. surgery. In this method, the coronary sinus is left below the
Asymptomatic cyanotic newborn do not need any active prosthetic tricuspid valve.66,67
treatment unless cyanosis is severe. Treatment consists of Carpentier’s repair15 consists of placating the atrialized
temporarily keeping the PDA open using prostaglandin portion of RV and narrowing the tricuspid valve annulus
(PG) E1 infusion (0.05–0.1 mcg/kg/min) until PVR drops. but, in a direction at right angles from that performed by
Occasionally, use of inhaled nitric oxide to reduce PVR Danielson. This results in a more normal-sized and shaped RV
has helped to improve pulmonary blood flow and hence than in Danielson’s repair. Carpentier also used annuloplasty
the systemic oxygenation. Such therapy is usually needed ring.15 Quaegebeur et al68 performed repair similar to that of
for a few days only, after which they can be safely weaned. Carpentier repair, but without using annuloplasty ring.
Intubation and positive pressure ventilation may help to Some surgeons argue that a simple closure of ASD with
manage pulmonary hypertension more effectively. Deep replacement of TV without plication of atrialized portion of
sedation and muscle relaxant may be necessary for few days RV may be adequate. This argument is based on a consideration
to manage pulmonary hypertension. Correction of metabolic that plication of atrialized portion of RV does not seem to
acidosis with bicarbonate infusions and inotropic infusions add any functional advantage to the RV. But, the widely-held
for low cardiac output will be needed.28 Few neonates may view69,70 is that plication of the atrialized portion of the RV
require surgical systemic-pulmonary shunt to maintain should be performed especially when the displacement of the
adequate pulmonary blood flow and thus, maintain adequate tricuspid valve is moderate or severe.69,70
systemic oxygen saturation. Cone procedure: Da Silva et al71 described a repair that
Features of heart failure from tricuspid regurgitation may consisted of mobilizing the anterior and posterior leaflets from
be treated with anti-failure medications such as Furosemide their anomalous attachments, rotating the detached edges
and Digoxin. of these leaflets clockwise and suturing them to the septal
Supraventricular tachycardia from accessory pathway or edge of the anterior leaflet at the level of true tricuspid valve
atrial flutter from enlarged atrium should be controlled using annulus. This creates a cone with its apex at the RV apex and
appropriate anti-arrhythmic medications. the base at the true tricuspid annulus. Septal leaflets, when
424 Restrictive PFO/ASD may require balloon atrial septostomy present are incorporated into this cone. ASD is closed as in the
in order to stabilize the baby for further management. While this other techniques. This procedure was performed with minimal
29
http://vip.persianss.ir
6 Fontan operation, of course, is usually preceded by either an 1. New York Heart Association (NYHA) III or IV.
aortopulmonary shunt in the newborn period and followed by 2. NYHA I and II, but with CT ratio of 0.65 or more.
a bidirectional Glenn operation, as a staged procedure.76 3. Significant cyanosis (80% or less; Hemoglobin 16 gm% or
congenital ValVular lesions
http://vip.persianss.ir
6
congenital ValVular lesions
a B
figures 13a and B: Selected cineangiographic frames in postero-anterior view from an adolescent with L-transposition of the great arteries
and Ebstein anomaly of left atrioventricular valve. A. Right-sided morphologic left ventricular (MLV) angiogram demonstrating smooth walled
ventricular chamber giving rise to the main pulmonary artery (PA); B. Left-sided morphologic right ventricular (MRV) cineangiogram showing
trebeculated ventricular chamber giving rise to the aorta (Ao). Radio-opaque ring of the St. Jude valve (SJV) is seen (which was inserted to
replace severely regurgitant Ebstinoid left atrioventricular valve at the age of 5 years). Pacemaker wires placed at the time of surgery, marker
pigtail (MPG) catheter and sternal wires are seen
Electrocardiogram Management
Electrocardiogram is characteristic with absence of Q wave in Patients with mild AV valve insufficiency may need
left precordial leads and presence of Q wave in V1 indicating periodic follow-up. Treatment of congestive heart failure
reversal of septal depolarization.86 Left atrial enlargement including afterload reducing agents may be needed in
and right ventricular dominance are other features. Atrio- moderate to severe AV valve insufficiency. Some of these
ventricular conduction block (prolonged PR interval through infants may require surgical repair or replacement of
428 3rd degree heart block) may be present. left AV valve later in life. Discussion of considerations
for double switch operation is beyond the scope of this Echocardiogram 29
chapter.
Echocardiogram will help to distinguish this lesion from
http://vip.persianss.ir
6 is usually normal in these lesions. Tricuspid regurgitation Cardiac Catheterization
may also occur secondary to chronic volume overload of
the right ventricle from free pulmonary regurgitation—with Cardiac catheterization may be indicated for a variety of
congenital ValVular lesions
or without associated pressure overload secondary to right reasons depending upon the etiology in a given patient. Right
ventricular outflow obstruction. These patients become atrial mean pressure may be elevated. However, in chronic
symptomatic over several years during long-term follow-up tricuspid regurgitation, right atrial enlargement and venous
after surgical repair. compliance may accommodate the regurgitant volume
leading to relatively lower right atrial mean pressure than
Clinical Presentation expected. Prominent ‘v’ wave in right atrial trace is indicative
of tricuspid insufficiency. Systemic desaturation occurs
Neonates present with cyanosis at birth. If the cause if there is right to left shunting at atrial level. RV systolic
of tricuspid regurgitation is transient such as persistent pressure may be elevated depending upon associated cardiac
pulmonary hypertension of newborn or myocardial depression lesions. Right ventricular end-diastolic pressure is elevated as
from birth asphyxia, this will resolve as the primary cause well. Right ventriculogram demonstrates the enlarged right
resolves and patent foramen ovale starts to close. Transient ventricle, reveals the severity of tricuspid regurgitation and
heart failure features may occur, but uncommon. In older outlines the right atrium that is usually enlarged.
children, presentation usually is chronic fatigue and exercise
intolerance. Clinical examination may include features of Management
heart failure, single S2, holosystolic murmur with thrill at
the left lower sternal border and sometimes a mid-diastolic In newborn with tricuspid regurgitation secondary to persistent
murmur may be heard at the left lower sternal border.29 pulmonary hypertension or myocardial depression, treatment
should be directed at the primary cause such as nitric oxide for
Investigations pulmonary hypertension. In newborn with isolated tricuspid
regurgitation, prostaglandin infusion may help decrease
systemic hypoxia until pulmonary vascular resistance decreases
Chest X-ray
enough to decrease right ventricular pressure. Heart failure
Chest X-ray shows severe cardiomegaly usually secondary may need diuretics and Digoxin. Other supportive therapy
to right atrial enlargement and right ventricular enlargement. depending upon the severity of the clinical manifestations will
Decreased pulmonary vascular markings are usually expected be required such as monitoring arterial blood gases, correction
in a newborn. In older children, this may not be present. of any acidosis, electrolyte abnormalities, providing assisted
ventilation, etc. Every attempt is made to avoid neonatal surgery
Electrocardiogram for tricuspid regurgitation which may include annuloplasty
alone, valve repair or valve replacement. DeVega tricuspid
Electrocardiogram shows right axis deviation, right atrial annuloplasty procedure was originally described in 1973 and is
enlargement and sometimes, right bundle branch block. This performed either by itself or along with another cardiac repair
may vary depending upon associated cardiac lesions and prior and provides excellent relief from tricuspid regurgitation.105,106
heart surgery. In older children, results of tricuspid valve surgery are better.
Although echocardiographic tricuspid regurgitation may
Echocardiography increase with time following repair, reintervention is rarely
necessary.107
Echocardiography is diagnostic and provides good
evaluation of severity and may help elucidate the mechanism sUMMARY AND CONCLUsION
of regurgitation. Objectives of echocardiography include
assessing the severity of tricuspid regurgitation using a In this chapter, Ebstein’s malformation of the tricuspid valve,
combination of chamber size and pulse, continuous wave Ebstein’s anomaly of the left-sided atrioventricular valve
Doppler and color Doppler imaging. Reversal of flow in vena in corrected transposition, tricuspid stenosis and tricuspid
cavae and hepatic veins are helpful in assessing severity. regurgitation were discussed.
Mechanism of tricuspid regurgitation including assessment In Ebstein’s anomaly of the tricuspid valve, there is
valve anatomy, subvalvar apparatus and coaptation of downward (apical) displacement of insertion of septal
leaflets should be assessed. In older children and adults, TEE and posterior leaflets along with valve dysplasia leading to
may help when transthoracic acoustic windows are poor and tricuspid regurgitation, right atrial enlargement and varying
the image quality is inadequate. Assessment of severity of degrees of atrialization of the right ventricle. It is a rare
other co-existing cardiac lesions should be performed as anomaly accounting for 0.3 – 0.6% of all congenital heart
430 well.103,104 defects. Differing presentations are seen which depend upon
severity of each component of lesion and associated lesions. 8. Yacobi S, Ornoy A. Is lithium a real teratogen? What can we
conclude from prospective versus retrospective studies. A
29
Mild cases may not be detected until adulthood. More
severe forms present during neonatal period or even in the review. Isr J Psychiatry Relat Sci. 2008;45:95.
http://vip.persianss.ir
6 30. Hornberger LK, Sahn DJ, Kleinman CS, et al. Tricuspid valve
disease with significant tricuspid insufficiency in the fetus:
51. Bharucha T, Anderson RH, Lim ZS, et al. Multiplanar review
of three-dimensional echocardiography gives new insights into
Diagnosis and treatment. J Am Coll Cardiol. 1991;17:167. the morphology of Ebstein’s malformation. Cardiol Young.
congenital ValVular lesions
31. Schiebler GL, Adams P Jr, Anderson RC, et al. Clinical 2010;20:40.
study of 23 cases of Ebstein’s anomaly of the tricuspid valve. 52. Yalonetsky S, Tobler D, Greutman M, et al. Cardiac magnetic
Circulation. 1959;19:165. resonance imaging and the assessment of Ebstein’s anomaly in
32. Celermajer DS, Bull C, Till JA, et al. Ebstein’s anomaly: adults. Am J Cardiol. 2011;107:767.
presentation and outcome from fetus to adult. J Am Coll 53. Tobler D, Yalonetsky S, Crean AM, et al. Right heart
Cardiol. 1994;23:170. characteristics and exercise parameters in adults with Ebstein’s
33. Flores Arizmendi A, Fernandez Pineda L, Quero Jiminez C, et anomaly: New Perspectives from cardiac magnetic resonance
al. The clinical profile of Ebstein’s malformation as seen from imaging studies. Int J Cardiol 2011 Aug 26 Epub ahead
fetus to the adult in 52 patients. Cardiol Young. 2004;14:55. of print. http://www.sciencedirect.com/science/article/pii/
34. Kanter RJ. Pearls for ablation in congenital heart disease. J S0167527311008291.
Cardiovasc Electrophysiol. 2010;21:223. 54. Zimmer EZ, Balzer S, Lorber A, et al. Fetal Ebstein’s anomaly:
35. Cappato R, Schluter M, Weiss C, et al. Radiofrequency current early and late appearance. Prenat Diagn. 2012;32:228.
catheter ablation of accessory atrioventricular pathways in 55. Andrews RE, Tibby SM, Sharland GK, et al. Predictors of
Ebstein’s anomaly. Circulation. 1996;94:376. outcome of tricuspid valve malformations diagnosed during
36. Delhaas T, Sarvaas GJ, Rijlaarsdam ME, et al. A multicenter, fetal life. Am J Cardiol. 2008;101:1046.
long-term study on arrhythmias in children wth Ebstein’s 56. Barre E, Durand I, Hazelset T, et al. Ebstein’s anomaly and
anomaly. Pediatr Cardiol. 2010;31:229. tricuspid valve dysplasia: prognosis after diagnosis in utero.
37. Bialostozsky D, Medrano GA, Munoz L, et al. Vectorcardio- Pediatr Cardiol. 2012;33:1391-6.
graphic study and anatomic observations in 21 cases of Ebstein’s 57. McElhinney DB, Salvin JW, Colan SD, et al. Improving
malformation of the tricuspid valve. Am J Cardiol. 1972;30:354. outcomes of fetuses and neonates with congenital displacement
38. Kumar AE, Fyler DC, Miettinen OS, et al. Ebstein’s anomaly: (Ebstein’s anomaly) or dysplasia of tricuspid valve. Am J
Clinical profile and natural history. Am J Cardiol. 1971;28:84. Cardiol. 2005;96:582.
39. Rowe RD, F Jreedom RM, Mehriz A, et al. The neonate 58. Ammash NM, Warnes CA, Connolly HM, et al. Mimics of
with congenital heart disease. In: Major prodems in clinical Ebstein’s anomaly. Am Heart J. 1997;134:508.
pediatrics. 2nd edition. Philadelphia: WB Saunders Company. 59. Watson H. Natural history of Ebstein’s anomaly of tricuspid
1981;5:101-9,515-28. valve in childhood and adolescence. Br Heart J. 1974;36:417.
40. Follah F, Hallidie-Smith KA. Unusual electrocardiographic 60. Radford DJ, Graff RF, Neilson GH. Diagnosis and natural
changes in Ebstein’s anomaly. Br heart J. 1972;34:513. history of Ebstein’s anomaly. Br Heart J. 1985;54:517.
41. Shiina A, Seward JB, Edwards WD, et al. Two-dimensional 61. Radford DJ, Graff RF, Neilson GH. Diagnosis and natural
echocardiographic spectrum of Ebstein’s anomaly: Detailed history of Ebstein’s anomaly. Br Heart J. 1985;54:517.
anatomic assessment. J Am Coll Cardiol. 1984;3:356. 62. Legius B, Van De Brugeng A, Van Deyk K, et al. Behavior
42. Rusconi PG, Anderson RH, Rigby ML, et al. Morphologic and of Ebstein’s anomaly: Single-center experience and mid-term
echocardiographic correlates of Ebstein’s malformation. Eur follow-up. Cardiology. 2010;117:90.
Heart J. 1991;12:784. 63. Rao PS, Chandar JS, Sideris EB. Role of inverted buttoned
43. Roberson DA, Silverman NH. Ebstein’s anomaly: Echocar- device in transcatheter occlusion of atrial septal defect or patent
diographic and clinical features in the fetus and neonate. J Am foramen ovale with right-to-left shunting associated with
Coll Cardiol. 1989;14:1300. previously operated complex congenital cardiac anomalies.
44. Celermajer DS, Dodd SM, Greenwald SE, et al. Morbid Am J Cardiol. 1997;80:914.
anatomy in neonates with Ebstein’s anomaly of the tricuspid 64. Danielson GK, Maloney JD, Devloo RAE. Surgical repair of
valve: Pathophyisologic and clinical implications. J Am Coll Ebstein’s anomaly. Mayo Clin Proc. 1979;54:185.
Cardiol. 1992;19:1049. 65. Danielson GK, Driscoll DJ, Mair DD, et al. Operative
45. Snider AR, Serwer GA, Ritter AB. Abnormalities of ventricular treatment of Ebstein’s anomaly. J Thorac Cardiovasc Surg.
inflow. In: Echocardiography in Pediatric Heart Disease. 2nd 1992;104:1195.
edition. St Louis: Mosby. 1996.pp.385-407. 66. Barnard CN, Schrire V. Surgical correction of Ebstein’s
46. Rusconi PG, Zuberbuhler JR, Anderson RH, Rigby ML. anomaly with prosthetic tricuspid valve. Surgery. 1963;54:302.
Morphologic and echocardiographic correlates of Ebstein’s 67. Kirklin JK. Christian Barnard’s contribution to the surgical
malformation. Eur Heart J. 1991;12:784. treatment of Ebstein’s malformation. Ann Thorac Surg.
47. Celermajer DS, Cullen S, Sullivan ID, et al. Outcome in neonates 1991;51:147.
with Ebstein’s anomaly J Am Coll Cardiol. 1992;19:1041. 68. Quaegebeur JM, Sreeram N, Fraser AG, et al. Surgery for
48. Andelfinger G, Shirali GS, Raunikar RA, et al. Functional Ebstein’s anomaly: The clinical and echocardiographic
pulmonary atresia in neonatal Marfan’s syndrome: Successful evaluation of a new technique. J Am Coll Cardiol.
treatment with inhaled nitric oxide. Pediatr Cardiol. 2001;22:525. 1991;14:1300.
49. Mararu D, Badano LP, Sarais C, et al. Evaluation of tricuspid 69. Timmis HH, Hardy JD, Watson DG. The surgical management
valve morphology and function by transthoracic three- of Ebstein’s anomaly. The combined use of tricuspid valve
dimensional echocardiography. Curr Cardiol Rep. 2011;13:242. replacement, atrioventricular plication and atrioplasty. J Thorac
50. Van Noord PT, Scohy TV, McGhie J, et al. Three-dimensional Cardiovasc Surg. 1967;53:385.
432
transesophageal echocardiography in Ebstein’s anomaly. 70. Hardy KL, Roe BB. Ebstein’s anomaly: Further experiences
Interact Cardiovasc Thorac Surg. 2010;10:836. with definitive repair. J Thorac Cardiovasc Surg. 1969;58:553.
71. Da Silva JP, Baumgratz JF, da Fonseca L, et al. The cone
reconstruction of the tricuspid valve in Ebstein’s anomaly. The
tricuspid atresia and stenosis. J Thorac Cardiovasc Surg.
1976;72:383.
29
operation: Early and mid-term results. J Thorac Cardiovasc 89. Marwah A, Suresh PV, Shah S, et al. Parachute tricuspid valve.
433
http://vip.persianss.ir
C hapter
Introduction blood flow. The atrial septum is usually intact; if not the defect
is usually a patent foramen ovale, although a secundum atrial
Congenital pulmonary valve disorders could be stenotic or septal defect may coexist.
regurgitant. Rarely the pulmonary valve could be absent or
atretic. The pulmonary valve disorder may be isolated or History
associated with other congenital heart diseases (CHD).
Pulmonary valvar or valvular stenosis is one of the more
Pulmonary valve anatomy common forms of congenital heart malformations and it has
been extensively studied since the original description of
The pulmonary valve separates the right ventricular outflow pulmonary valve stenosis by John Baptist Morgagni in 1761.3
tract from the pulmonary artery. In normal conditions this The anatomical details of the anomaly was described in his
valve prevents regurgitation of the deoxygenated blood classic monograph.
from the pulmonary artery back to the right ventricle. It is a
semilunar valve and is located anterior, superior and slightly Incidence
to the left of the aortic valve. Pulmonary valve is formed by
three cusps, each with a fibrous node at the midpoint of the Isolated pulmonary valve stenosis is found in 80 to 90 percent
free edges as well as lunulae, which are the thin, crescent- of all patients with right ventricular outflow obstruction and 8
shaped portions of the cusps that serve as the coaptive surfaces to 10 percent of patients with CHD.
of the valve. The cusps of the pulmonary valve are supported Familial occurrence of pulmonary stenosis has been
by free-standing musculature with no direct relationship with reported. Campbell4 found a 2.1 percent incidence of cardiac
the muscular septum; its cusps are thinner and lack a fibrous disease, usually pulmonary stenosis or tetralogy of Fallot
continuity with the anterior leaflet of the right atrioventricular (TOF), in siblings of patients with pulmonary stenosis. In the
valve.1 The cusps of the pulmonary valve are defined by their Second Natural History Study of Congenital Heart Defects, the
relationship to the aortic valve and are thus termed anterior or occurrence of definite and possible congenital heart defects in
non-septal, right and left cusps. They can also be defined by 1,356 siblings of 449 patients with valvar pulmonary stenosis
their relationship to a commissure found in the pulmonary and was 1.1 and 2.1 percent respectively.5
aortic valves and hence termed right adjacent (right facing),
left adjacent (left facing) and opposite (non-facing). The Embryology and Pathology
pulmonary valve, like the other three cardiac valves, is formed
by the endocardial folds that are supported by the internal The exact embryologic process resulting in pulmonary valve
plates of dense collagenous and elastic connective tissue and stenosis is not well understood. Maldevelopment of the distal
are continuous with the cardiac skeleton.2 part of the bulbus cordis,6 fetal endocarditis7 and genetic factors
with multiple somatic abnormalities8 have been proposed.
Pulmonary Stenosis In the classic form of pulmonary valve stenosis, the valve is
conical or dome shaped and two to four raphes may be visible,
Isolated pulmonary valve stenosis is a form of acyanotic con- but there is no separation into the valve leaflets.9 As primarily
genital malformation with normal or diminished pulmonary there is an inherent medial abnormality, the pulmonary trunk
is usually dilated. Less commonly, the valve may be diffusely Clinical Features 30
thickened with one, two or three leaflets and commissural fu-
sion. The unicuspid or bicuspid pulmonary valve is generally Symptoms
http://vip.persianss.ir
6 Palpation
Auscultation
The first heart sound is normal and in mild-to-moderate
cases it is followed by a pulmonary ejection click. The click
corresponds to the time when the doming pulmonary valve
reaches its open position. The more severe the stenosis, the
earlier in systole the click occurs, until it merges with the
first heart sound and becomes inaudible. The intensity of the
click varies with respiration, decreasing during inspiration
and increasing during expiration. The second heart sound
is usually split and the degree of splitting is proportional Figure 1: Schematic illustration of valvar pulmonic stenosis. In mild
to the degree of stenosis. The split may become fixed stenosis, the ejection click (EC) is clearly separated from the first heart
in severe stenosis as a result of fixed stroke volume. The sound (S1). The murmur starts with the click, peaks in early systole,
and ends way before the aortic component of the second heart sound
intensity of pulmonary component decreases with increasing (A2). The pulmonary component of the second heart sound (P2) is
obstruction. A fourth heart sound is heard at the left sternal normal or decreased in intensity. In moderate pulmonic stenosis,
border with severe stenosis. The systolic murmur of valvular the click is closer to the first heart sound, the ejection murmur peaks
pulmonary stenosis increases with severity, radiates over later in the systole and the murmur reaches A2 and the second heart
sound is widely split with soft pulmonary component. In severe valvar
the entire precordium and neck, characteristically heard in obstruction, the click is either absent or occurs so close to S1 that it
the back and is ejection in quality with maximal intensity at cannot be heard separately, and the murmur peaks late in systole and
the upper left sternal border (Figure 1). Patients with severe extends beyond the A2. The second heart sound is widely split with an
stenosis and right heart failure may have an unusually soft extremely soft or inaudible P2
murmur because of low cardiac output.
In patients between 2 and 20 years of age, a pure R wave is
Diagnosis present in lead V112 (Figure 2).
In pulmonary stenosis, the electrocardiogram findings of left
Electrocardiogram axis deviation with right ventricular hypertrophy is suggestive
of Noonan syndrome (dysplastic pulmonary valve).
In mild pulmonary stenosis, slight rightward deviation of QRS
frontal axis and right ventricular conduction delay is usually Chest X-ray
seen on the electrocardiogram (ECG).
In moderate pulmonary stenosis only 10 percent of patients The most distinctive feature in valvular pulmonary stenosis
have a normal tracing. Right-axis deviation is usually present. is a prominent main pulmonary artery resulting from post-
The R:S ratio in V1 is usually more than 4:1 and the R wave is stenotic dilatation, which is present in 80 to 90 percent of the
typically less than 20 mm. The T waves in the right precordial cases. The apex of the heart is usually rounded and pointing
leads are upright in approximately 50 percent of patients. downwards (Figure 3). A left aortic arch is virtually always
In severe pulmonary stenosis, the mean frontal QRS axis is present. When heart failure develops, marked cardiomegaly
usually more than 110 degrees. A pure R, Rs or qR is usually results owing to right atrial and right ventricular enlargement
seen in right precordial leads and the R wave is usually more and pulmonary vascularity is decreased as a result of reduced
than 20 mm. The R:S ratio in V6 may be less than 1. The pulmonary flow.
T wave may be upright or inverted in the right precordial leads
and the P waves are abnormally tall and peaked in lead II and Echocardiography
in right precordial leads.
In lead V1, the height of R wave in millimeters, multiplied The two-dimensional echocardiogram clearly demonstrates
436 by 5 approximates the right ventricular pressure in mm Hg. the typical features of the stenotic pulmonary valve from the
30
Cardiac Catheterization
The right ventricular pressure compared with systemic arterial
pressure and the pressure gradient across the pulmonary valve
are the most important measurements made at catheterization.
A resting right ventricular pressure more than 35 mm Hg and
Figure 3: Fluroscopic image in anterioposterior view in a 3 month old a pressure gradient across the pulmonary valve of more than
infant with severe valvar pulmonic stenosis showing cardiomegaly with 10 are considered abnormal. An end-hole catheter is used to
right ventricle, right atrium and main pulmonary artery dilatation with
oligemia
obtain carefully the withdrawal pressure recordings from the
pulmonary artery to the body of the right ventricle to assess
the severity and location of stenosis. The right ventricular
standard and high parasternal short-axis and long-axis views end-diastolic pressure may be normal, but usually is elevated
as well as the subcostal sagittal views. The leaflets are usually with severe obstruction or right ventricular failure. The right
thickened, doming with restricted systolic motion. Post- atrial pressure is normal in mild-to-moderate obstruction, but
stenotic dilation of the main and branch pulmonary arteries, tall right atrial ʻaʼ waves are seen with severe obstruction.
right ventricular hypertrophy and anatomy of the tricuspid Pulmonary artery pressure is normal in mild cases, but is
valve can be assessed. Features of dysplastic pulmonary valve decreased and dampened in severe cases. This depression 437
http://vip.persianss.ir
6
Congenital Valvar Lesions
Figure 4: Continuous wave Doppler from a 8-year-old boy with severe pulmonary stenosis
Treatment
A B
Figures 7A and B: Pulmonary balloon valvuloplasty (PBV) done with a loop in right atrium, like an upper limb approach. A. 3.5 × 20 mm
percutaneous transluminal coronary angioplasty (PTCA) balloon passed over 0.014″ floppy PTCA guidewire; B. Stenotic pulmonary valve dilated
with 6 × 20 mm Tyshak balloon
(Figures 7A and B), have increased the success and safety of Surgical Valvotomy
balloon dilation in this group of patients, such that it is now
considered the treatment of choice. The use of angled-tip Since the advent of pulmonary valvuloplasty, surgical valvotomy
catheters and high-torque wires has facilitated crossing the tiny is reserved for patients with dysplastic pulmonary valve resistant
pulmonary valve orifice. to dilation or patients with multiple levels of fixed obstruction.
The short and intermediate-term results of pulmonary Valvotomy can be achieved using either a closed or open
valvuloplasty in children and adults with typical pulmonary technique through the main pulmonary artery. Simple valvotomy
valve stenosis have been excellent.15 Long-term outcome has is ineffective, when the pulmonary valve is dysplastic. Partial
been reported in smaller series of patients.16 The significantly or more often total removal of the pulmonary valve may be
lower success rate for patients with dysplastic pulmonary necessary. In addition, insertion of a trans-annular patch may be
valves is not surprising given the anatomic features of these necessary to enlarge the hypoplastic annulus and main pulmonary
valves. The mechanism of obstruction relief in patients with artery. These patients are usually left with at least moderate
typical doming pulmonary valves has been shown to be pulmonary insufficiency, which is well tolerated on follow-up.
commissural splitting, in most cases. Long-term relief of obstruction after pulmonary valvotomy is
Most patients who have been treated with pulmonary excellent, and restenosis is uncommon.
valvuloplasty have some degree of pulmonary insufficiency.
The incidence of moderate pulmonary insufficiency early Indications for the Procedure
after valvuloplasty has been variably reported from less than
5 percent to as much as 24 percent at intermediate-term Currently pulmonary balloon valvuloplasty is the first line
follow-up. of treatment for pulmonary valve stenosis at any age.
439
http://vip.persianss.ir
6 Valvuloplasty should be performed in any symptomatic patient pulmonary regurgitation. Ventricular stiffness is thought to
as soon as the diagnosis is made including infants with critical increase with hypertrophy or increased fibrosis.
pulmonary valve stenosis, but if this is unsuccessful, surgery
Congenital Valvar Lesions
http://vip.persianss.ir
6 and postnatally pathognomonic. In addition to these key
findings, typical features of the TOF, VSD, atrial septal defect,
coarctation of aorta and tricuspid atresia can be present.
Congenital Valvar Lesions
Frequency
Absent pulmonary valve is a rare and severe disease,
particularly in the newborn and the fetus. The overall
frequency of APV is not known, because in epidemiological
studies APV is not categorized as a malformation on its own.
However, several reports quote a prevalence of 3 to 6 percent
of APV in patients with TOF.20
Management
The life-threatening symptom is respiratory distress in the
newborn. It occurs predominantly in the Fallot-type APV. Air-
way management as a primary procedure involves intubation,
mechanical ventilation and extracorporeal membrane oxy-
genation in some infants. It is usually performed under emer-
gency circumstances. Urgent complete surgical repair should
relieve the compression of the tracheobronchial tree. This
is achieved by combined anterior and posterior plication
Figure 11: Transthoracic parasternal short-axis view at the basal level of the pulmonary arteries or by translocation of the pulmo-
with color Doppler demonstrates severe, hardly turbulent pulmonary nary artery anterior to the aorta and away from the airways,
insufficiency (PI) in early diastole in a patient with absent pulmonary ‘maneuver de Lecompte’ procedure.
valve Repair of pulmonary insufficiency and stenosis requires
placement of a valve conduit (homograft or heterograft) in the
right ventricular outflow tract. Repair in the Fallot-type APV
2. Infantile group presenting commonly as critically ill- includes additional closure of the VSD with a patch. In infants
newborns with severe respiratory distress requiring with non-Fallot APV, the ductus arterious must be closed.
mechanical ventilation. Asymptomatic infants can undergo repair within the first 6 to
Recently, the fetus with APV became another important 12 months. Repair should however not be delayed for too long
group. During the first half of pregnancy, the diagnosis in order to avoid the harmful effect of the dilated pulmonary
seems to be incomplete. In the fetus with Fallot-type APV, arteries on the tracheobronchial tree. Apart from conduit
a distinct echocardiographic feature is the right-to-left shunt replacement in children as they grow, other reinterventions
during systole and diastole across the unrestricted VSD may be required, mainly for persistent respiratory symptoms.
secondary to the pressure-volume overload of the right Midterm outcome for patients with Fallot-type APV who
ventricle. Furthermore, the risk of survival of the fetus with survive the initial repair is favorable. Repeat plication of
this condition in later pregnancy may be related to cessation pulmonary arteries and/or utilization of intrabronchial
of the physiological flow from the pulmonary artery into the expandable stents may improve the outcome in patients with
descending aorta through the ductus arteriosus prior to its persistent airway compression who cannot be weaned from 443
premature closure. the respirator because of severe tracheobronchial malacia.
http://vip.persianss.ir
6 Conclusion 8. Noonan JA. Hypertension with Turner phenotype: A new
syndrome with associated congenital heart disease. Am J Dis
Total or subtotal absence of pulmonary artery leaflets is defined Child. 1968;116:373-80.
Congenital Valvar Lesions
444
C hapter
Congenital mitral valve diseases are a heterogeneous group, Embryology and Anatomy
often complex and are commonly associated with other
congenital heart diseases (CHD) (Table 1). They are rare Embryology
as isolated lesions, occurring in approximately 4 of 1,000 Formation of the atrioventricular (AV) valve is completed
children with CHD. The spectrum of mitral valve disease are early in embryologic development (by approximately 14
shown in Table 1. Mitral valve diseases have been subdivided to 19 weeks of gestation). The mitral valve is formed from
into stenotic, regurgitant or mixed lesions. This chapter will endocardial cushions that originate both at the AV orifice and
focus on the regurgitant lesions and congenital mitral valve from muscular tissue of the ventricular wall. This process
prolapse. The mitral stenotic lesions have been dealt in is driven by regulatory protiens that are expressed in genes
Chapter 27. in the local myocytes in a time dependent manner. Specific
mutations altering the genetic milieu in which the AV valve
formation occurs results in congenital malformations of the
Table 1
atrioventricular valves. The papillary muscles are derived
Spectrum of congenital anomalies of mitral valve from the horseshoe-shaped myocardial ridge, which forms
along the left ventricular wall. Delamination and selective
1.
Supramitral ring (SMR) or membrane apoptosis leads to the formation of deep trabeculae leading to
2.
Hypoplasia of the mitral apparatus
the formation of papillary muscles. Chordae tendineae form
3.
Dysplasia of the mitral valve
4.
Parachute mitral valve from the process of selective apoptosis of the endocardial
Cleft mitral leaflet
5. cushions. These processes create the four major components
6.
Abnormal mitral arcade of the mitral valve appartus, which are the annulus, leaflets,
7.
Double orifice mitral valve chordae tendineae and the papillary muscles.
8.
Accessory mitral valve tissue/orifice
9.
Ebstein’s anomaly of the mitral valve
10.
Mitral valve prolapse Anatomy
11.
Mitral regurgitation due to other congenital causes:
i. Papillary muscle dysfunction due to ischemia The normal mitral valve consists of two leaflets and is
caused by: suspended from the fibrous mitral valve annulus at the
– Anomalous origin of the left coronary artery from level of the atrioventricular junction (Figure 1). The mitral
the pulmonary artery (ALCAPA)
annulus is derived from the fibrous skeleton of the heart. This
ii. Cardiomyopathy
– Dilated cardiomyopathy fibrous ring surrounding the mitral valve is part of a larger
– Hypertrophic cardiomyopathy fibrous structure, which attaches to the right and left fibrous
– Non-compaction of left ventricle trigones, the membranous septum and the aortic root. As this
iii. Storage disease/infiltration is discontinuous in the posterior aspect, there is an increasing
– Hurler disease risk for posterior annular dilatation. There is fibromuscular
– Amyloidosis
continuity between the mitral valve annulus and the aortic
iv. Connective tissue disorders
valve. The anterior mitral leaflet is in continuity with the
http://vip.persianss.ir
6
Congenital Valvar Lesions
noncoronary cusp and the left coronary cusp of the aortic are attached to the anterior and posterior mitral valve leaflets
valve. Active contraction of the annulus fibrosus begins at via the chordae tendineae. Hence, ventricular geometry can
the onset of atrial contraction and continues through the affect the function of the papillary muscles.
ventricular systole leading to a substantial reduction in the The four anatomic components of the mitral valve function
annular orifice area. On further contraction of the muscle fibers to allow unobstructed blood flow from the LA to the left
the mitral leaflets assume a concave shape, which contributes ventricle (LV) during diastole and to maintain competent
to an effective seal. The mitral valve leaflets (anterior closure during systole. The leaflets open fully during the early
and posterior) consist of collagen fibrosa and spongiosa rapid-filling phase of diastole. They begin to close passively
peripherally and mucoid myxomatous tissue centrally. as LV pressure and volume increase. Then, the leaflets reopen
The anterior mitral leaflet is larger, sail-like and guards briefly as atrial contraction occurs, adding additional volume
approximately two-thirds of the left atrioventricular orifice, to the LV. During atrial contraction, annular contraction
but occupies only one-third of its annular circumference. The effectively decreases the circumference of the mitral valve
height of the anterior mitral leaflet often is used clinically by 20 to 30 percent throughout systole. Contraction of the
to size the mitral valve prostheses. The posterior leaflet is papillary muscles serves to maintain the length of the chordae
smaller, more rectangular and guards approximately one- under the pressure that develops during systole.
third of the left atrioventricular orifice, but occupies about
two-thirds of its annular circumference. The posterior Classification
leaflet is typically subdivided into three scallops, denoted
P1, P2, and P3. These scallops oppose the A1, A2, and A3 The congenital mitral valve diseases can be classified according
regions of the anterior mitral leaflet (Figure 2). The leaflets to three criteria: hemodynamic, anatomic and functional. The
free edge is termed the bare or membranous zone and the valves can be hemodynamically predominantly regurgitant or
remainder part of the leaflet is called the rough zone. The two stenotic. Anatomically, the congenital mitral valve anomalies
leaflets are separated by the anterolateral and posteromedial can be those with nondysplastic leaflets and those with
commissures. The valve leaflets are normally prevented from dysplastic leaflets. The annular dilatation can occur with
prolapsing into the left atrium (LA) by the tendinous cords, nondysplastic leaflet anatomy, with or without elongation
the chordae tendineae. The chordae tendineae are a complex of the chordae or the papillary muscle. They can be seen in
network of collagenous cord-like structures that extend from anomalies with significant volume loading of the left ventricle
the free edges of the mitral valve leaflets and insert into the like in large ventricular septal defect or large patent ductus
papillary muscles. The two papillary muscles, the anterolateral arteriosus. The dysplastic leaflets usually have a lack of
and posteromedial, arise from the ventricular free wall. They valvular tissue.
446
The anatomic classification by the STS-Congenital Heart hypoplasia. Group B is further subdivided into 31
Surgery Nomenclature and Database Committee has classified parachute mitral valve, hammock mitral valve and
congenital mitral valve disease into four types. The type 1 papillary muscle hypoplasia.
A B
Figures 3A and B: Echocardiography from a child with Marfan syndrome: A. Parasternal modified view showing myxomatous thickened 447
redundant leaflets of mitral valve; B. Apical four-chamber view showing prolapse of both leaflets of mitral valve (arrow). LA = Left atrium;
LV = Left ventricle; MV = Mitral valve; RA = Right atrium; RV = Right ventricle.
http://vip.persianss.ir
6 coaptation and valvular retraction during the healing phase vulnerable to ischemia and any disturbance in coronary
of endocarditis. Destruction of the mitral valve leaflets can perfusion may result in papillary muscle dysfunction. When
also occur in patients with penetrating and non-penetrating ischemia is transient, it results in temporary papillary muscle
Congenital Valvar Lesions
trauma. The MR associated with drug exposure also results dysfunction and may cause transient episodes of MR that
from anatomical changes in the valve leaflets. are sometimes associated with attacks of angina pectoris or
pulmonary edema. When ischemia of papillary muscles is
Abnormalities of the Mitral Annulus severe and prolonged, it causes papillary muscle dysfunction
and scarring, as well as chronic MR. The posterior papillary
The mitral annulus is saddle shaped and measures muscle, which is supplied by the posterior descending branch
approximately 10 cm in circumference in adults. It is soft of the right coronary artery, becomes ischemic and infarcted
and flexible and contraction of the surrounding LV muscle more frequently than does the anterolateral papillary muscle;
during systole causes the annular constriction that contributes the latter is supplied by diagonal branches of the left anterior
importantly to valve closure. The MR secondary to dilation descending coronary artery and often by marginal branches
of the mitral annulus can occur in any form of heart disease from the left circumflex artery as well. Ischemia of the
characterized by dilation of the LV, especially dilated papillary muscles is due to hypoxia, severe anemia, shock,
cardiomyopathy and also in post-tricuspid shunt lesions coronary arteritis of any cause or an anomalous left coronary
causing LV volume overloading. LV submitral aneurysm artery. Infact this is to be carefully looked for especially in
is a cause of annular MR commonly seen in sub-Saharan children. Infarcted and hyperechoic papillary muscle is
Africa due to a congenital defect in the posterior portion of an important echocardiographic criteria and corroborative
the annulus. Diagnosis by transesophageal echocardiography evidence of ALCAPA.
(TEE) and surgical repair have been reported. Various other disorders of the papillary muscles may also
Annular calcification may also be accelerated by an be responsible for the development of MR. These include
intrinsic defect in the fibrous skeleton of the heart, as occurs congenital malposition of the muscles; absence of one
in the Marfan and Hurler syndromes. In these two latter papillary muscle, resulting in the so-called parachute mitral
syndromes, the mitral annulus is not only calcified, but also valve syndrome and involvement or infiltration of the papillary
dilated, further contributing to MR. muscles by a variety of processes including abscesses,
granulomas, neoplasms, amyloidosis and sarcoidosis.
Abnormalities of the Chordae Tendineae
Left ventricular dysfunction: LV dilatation of any cause
The abnormalities of the chordae tendinae are important including ischemia due to ALCAPA can alter the spatial
causes of MR. Lengthening and rupture of the chordae relationships between the papillary muscles and the chordae
tendineae are cardinal features of the MVP syndrome. The tendineae and thereby result in functional MR. There may
chordae may be congenitally abnormal; rupture may be be additional ischemic damage to the papillary muscles,
spontaneous (primary) or may occur as a consequence of dilation of the mitral valve ring and/or loss of systolic annular
infective endocarditis, trauma, rheumatic fever or, rarely, contraction contributing further to MR. The incidence and
osteogenesis imperfecta or relapsing polychondritis. In most severity of regurgitation vary inversely with the LV ejection
patients, no cause for chordal rupture is apparent other than fraction and directly with the LV end-diastolic pressure.
increased mechanical strain. Chordae to the posterior leaflet Other causes of MR include obstructive hypertrophic
rupture more frequently than those to the anterior leaflet. cardiomyopathy (HCM), the hypereosinophilic syndrome,
Patients with idiopathic rupture of mitral chordae tendineae endomyocardial fibrosis, left atrial myxoma and various
frequently exhibit pathological fibrosis of the papillary congenital anomalies including cleft anterior leaflet.
muscles. It is possible that the dysfunction of the papillary Irrespective of cause, severe MR is often progressive, since
muscles may cause stretching and ultimately rupture of the enlargement of the LA places tension on the posterior mitral
chordae tendineae. Chordal rupture may also result from acute leaflet, pulling it away from the mitral orifice and thereby
LV dilation, regardless of the cause. Depending on the number aggravating the valvular dysfunction. Similarly, LV dilatation
of chordae involved in rupture and the rate at which rupture increases the regurgitation, which in turn enlarges the LA and
occurs, the resultant MR may be mild, moderate or severe and LV further, causing chordal rupture and resulting in a vicious
acute, subacute or chronic. circle; hence the aphorism MR ‘begets’ MR.
Cleft mitral valve: This rare anomaly (Figures 4A and
Involvement of the Papillary Muscles B) was found by echocardiography in 10/13,400 children
(0.75/1,000). A cleft in the anterior mitral cusp (less often,
Diseases of the LV papillary muscles are a frequent cause the posterior leaflet) is occasionally noted without an AV
of MR. Because these muscles are perfused by the terminal septal defect. There is no ‘gooseneck’ deformity and the
448 portion of the coronary vascular bed, they are particularly mitral annulus and leaflets are otherwise normal. The cleft
31
points anteriorly towards the LV outflow tract, unlike an orifice can vary and the border of the accessory orifice is
atrioventricular septal defect in which the cleft (commissure) usually devoid of chordae tendineae. In some cases, chordae
in the left atrioventricular valve points posteriorly towards may insert into an independent papillary muscle.
the inlet interventricular septum. Cleft leaflet could be termed Accessory mitral orifice is best visualized in parasternal
partial or complete depending upon its extension to mitral short axis and subcostal four-chamber view with color Doppler
valve annulus. One of the important reasons to make this interrogation. An abnormal position and orientation of MR
differentiation of isolated clefts from AV clefts is also that the jet may help to suspect this condition and warrants further
specialized conduction tissue differs so importantly between evaluation in different views. This condition is sometimes
these two lesions. About half of these clefts are isolated and associated with transposition of great arteries, partial
the rest associated with other congenital cardiac anomalies, atrioventricular septal defect and interrupted inferior vena cava.
including secundum atrial septal defects. There is a variable Mitral arcade: The tips of the two papillary muscles of the
degree of MR that depends on the degree of separation of the left ventricle are connected by a fibrous cord to which the
tissue on each side of the cleft and the chordal support, but free edge of the anterior leaflet is attached, either directly or
often clefts are not accompanied by significant regurgitation. by short chordae tendineae. The entity was first described in
Double-orifice mitral valve: An accessory bridge or limbus 1967 by Layman and Edwards. The entity has also been called
of tissue may partially or completely divide the mitral inlet Hammock mitral valve. In most patients, there is severe MR
into two orifices, termed as DOMV. It can cause both mitral from tethering of leaflet. In a few cases, MS has also been
stenosis (MS) and MR, with regurgitation in 45 to 50 percent described and involvement of tricuspid valve has rarely been
of the cases. These orifices are usually unequal, with the reported with AV valve regurgitation of both AV valves. The
smaller orifice directed towards the anterolateral commissure age at presentation or death varies widely. Most patients
(41%) or the posteromedial commissure (44%). In the latter, present in infancy, a few in early childhood and very rarely
atrioventricular septal defects are common (90%), and mitral in adults.
regurgitation is often present. This is described under LV Ebstein's Anomaly of Mitral Valve: This is a rare anomaly
inflow obstructions obstructions (Chapter 27). with very few published case reports. Here, the LA is dilated
Accessory mitral orifice: This abnormality results from and the posterior leaflet of mitral valve, which is dysplastic,
a circular deficiency of mitral leaflet tissue. The size of the is displaced downward with normal insertion of anterior 449
http://vip.persianss.ir
6 mitral leaflet into the ventricular septum (above the septal Clinical Features
tricuspid leaflet). Few case reports have shown associated
thin left ventricular wall. This abnormality is best visualized Symptoms
Congenital Valvar Lesions
A B
Figures 5A and B: Various phases of the prolapsed mitral valve (in the present case the cause
of prolapse was ruptured mitral valve chordae) 451
http://vip.persianss.ir
6 severity, radionuclide gated or first pass blood-pool imaging percent have died or undergone surgical correction. This latter
may be helpful in instances in which the echocardiographic series included many patients who were initially symptomatic
images are suboptimal or there is a discrepancy between the or had LV dysfunction or AF and thus might be considered to
Congenital Valvar Lesions
http://vip.persianss.ir
6
Congenital Valvar Lesions
A B
Figures 6A and B: Transthoracic echocardiogram in parasternal long-axis view with color Doppler shows grade II mitral valve prolapse (MVP)
with mitral regurgitation (MR). LA = Left atrium; LV = Left ventricle
http://vip.persianss.ir
6 for associated other cardiac and non-cardiac conditions. Their with many physicians who continue to stick to contemporary
first degree relatives should be evaluated for MVP and other guidelines.
connective tissue disorders.
Congenital Valvar Lesions
457
http://vip.persianss.ir
C hapter
32 Mitral Atresia
PATHOLOGY Atria
The description of pathologic features will be confined to The left atrium may be small and hypoplastic in most cases,
mitral atresia with normal aortic root. The pathology of mitral but the left atrial wall is thick and hypertrophied. Endocardial
32
fibroelastosis of LA may be present.3,11-13 The right atrium is subvalvar and 1 combined) out of a total of 52 cases. In another
always enlarged and hypertrophied. clinical study of 40 patients, 11 (27%) had pulmonary stenosis
Mitral Atresia
or atresia and 29 (73%) had no pulmonary stenosis.18 Of note,
Atrial Septum coarctation of aorta has not been reported in association
with this lesion when pulmonary stenosis or atresia was
Patent foramen ovale or an atrial septal defect is usually present;1,3,18 this is presumably because of fetal flow patterns
present; patent foramen ovale is seen in approximately two- as reviewed elsewhere19 and in the chapter on tricuspid atresia
thirds and atrial septal defect in one-third.9 The atrial defect in this book (Chapter 28).
may be restrictive and rarely, intact atrial septum may be
present; in such cases levoatriocardinal vein14,15 may partially Other Associated Defects
decompress the completely obstructed left atrium. Other
communications between left atrium and coronary sinus may Ductus arteriosus is patent in nearly 80 percent patients.9
be seen. Communications between left atrium and coronary sinus are
commonly seen. Persistent left superior vena cava may be
Ventricles seen in some patients. Abnormalities of both systemic and
pulmonary venous return may be present especially when
Univentricular hearts are most common with mitral atresia associated with heterotaxy syndrome.
with normal aortic root; most of these are right ventricular
type and a few have two ventricles with atrioventricular Extracardiac Anomalies
concordance. Double outlet right ventricle and double inlet
left ventricle with imperforate left atrioventricular valve, Major extracardiac anomalies are present in nearly half of the
though rare, have been reported. In the pathologic specimens patients. Heterotaxy (asplenia or polysplenia) may be seen in
examined by Thiene et al,1 15 of the 30 specimens were right nearly 25 percent of patients.3
ventricular type of univentricular heart, nine left ventricular
type, five were biventricular and one double inlet left ventricle. PATHOPHYSIOLOGY
When there are two ventricles, the majority of patients
have small left ventricles communicating with right ventricle Pulmonary venous blood from the left atrium exits via the atrial
via a small ventricular septal defect (VSD). Approximately 10 septal defect into the right atrium and mixes with systemic
percent of cases had normal sized left ventricles.3 The right venous return. If the interatrial communication is restrictive,
ventricle is always large and hypertrophied. pulmonary venous congestion and edema develop. If the atrial
septum is intact, the neonate is unlikely to survive unless there
Ventricular Septum is an alternative drainage such as levoatriocardinal vein.14,15
Once in the right atrium, the blood is passed on to the right
In the presence of two ventricles, the majority have a small or single ventricle via the tricuspid valve. The blood is then
VSD, although large VSDs have been reported. distributed into the aorta and pulmonary artery; the relative
flows into the two circuits are dependent upon the resistances
Great Vessels offered by the respective circulations. This results in systemic
arterial desaturation in all patients with mitral atresia. The
Transposition of the great arteries was stated to be degree of desaturation is proportional to the degree of right
frequent,9,16,17 but was present only in 30 percent of cases ventricular outflow obstruction, which is either at valvar
reported by Watson.3 By definition, the aortic valve and aortic and/or subvalvar level. In cases of pulmonary atresia, the
root are near normal in size. Right aortic arch, coarctation of pulmonary blood flow is derived from either via the patent
the aorta and interrupted aortic arch have been reported. In ductus arteriosus or through aortopulmonary collateral
the Watson series, right aortic arch was present in 8 percent vessels.
hearts, coarctation of the aorta was seen in 22 percent cases
and interrupted aortic arch was found in 4 percent specimens.3 CLINICAL FEATURES
Coarctation of the aorta and interrupted aortic arch were seen
only in subjects with normal pulmonary valve. Clinical presentation is largely dependent upon the patho
In the majority of patients, the pulmonary valve is normal physiology related to the amalgamation of associated lesions
and not stenotic; however, valvar and/or subvalvar stenosis seen in these patients. The scenarios include pulmonary
or atresia may be present in 25 to 30 percent of cases. In venous congestion secondary to interatrial obstruction,
series analyzed by Watson and colleagues,3 pulmonary atresia decreased pulmonary blood flow secondary to severe
was seen in four and pulmonary stenosis in 11 (8 valvar, 2 pulmonary stenosis or atresia and increased pulmonary blood 459
http://vip.persianss.ir
6
flow causing volume overload and heart failure in the absence Electrocardiogram
of pulmonary stenosis.
Congenital Valvar Lesions
These patients usually present as neonates (usually in Tall, peaked P waves consistent with right atrial enlargement
the 1st week of life) with cyanosis or difficulty in breathing. are present in many patients. Right-axis deviation is seen
Cyanosis in the newborn, in the presence of pulmonary in most patients and a few cases (12%) may show left-axis
stenosis or atresia is due to diminished pulmonary blood flow deviation. Right ventricular hypertrophy is seen in almost all
and complete-mixing of the pulmonary and systemic venous patients. Q wave in right precordial leads is commonly seen;
returns in the right atrium and the right ventricle. Cyanosis a qR pattern in right precordial leads is a fairly consistent
due to diminished pulmonary blood flow is manifested as the feature in one study.3
patent ductus arteriosus begins to constrict. Cyanotic spells
are occasionally noted in infants. Features suggestive of Echocardiography
increased pulmonary blood flow and congestive heart failure
are presenting symptoms in nearly half of the patients; these Echocardiogram is useful in the diagnosis and provides nece
are the patients without any pulmonary stenosis. The clinical ssary information for planning effective clinical management.
features of congestive heart failure appear as the pulmonary Evaluation of cardiac anatomy in subcostal, apical, parasternal
vascular resistance drops with the increasing age of the and suprasternal notch views provides complete assessment.
baby. In babies with interatrial obstruction, tachypnea and/or Key structure to define is the crux cordis, the spatial relationship
dyspnea along with cyanosis may be the presenting features; between atrial and ventricular septae and the atrioventricular
these may be occur shortly after birth or weeks and months (AV) junction.22 It is possible to visualize the atretic atrial floor
following birth as and when the interatrial communication in cases with absent connection vs imperforate valve in cases
becomes restrictive. In babies with intact atrial septum (rare) with imperforate valve membrane in the majority of patients,22
the presentation will be immediately after birth. although this distinction may not be important in terms of
Later during infancy, failure to thrive, irritability, lethargy diagnosis or management. Another important distinction to
and dyspnea may be present. Exercise intolerance is present make is whether the patent right-sided AV valve represents one
in children who live beyond infancy. Clubbing may be present AV valve, as in complete AV septal defect or it represents one AV
later in infancy and childhood.3,18,20 valve and the other AV valve is atretic (Figures 1A to D). This
Diminished femoral pulses may be seen in patients with determination is important with regard to clinical management.
aortic coarctation and as mentioned above, coarctation of the In the former with complete AV septal defect, there is usually
aorta is present in only patients who do not have pulmonary no left atrial hypertension. In the latter, with mitral atresia, there
stenosis. The precordial impulses show either hyperdynamic is a potential for a hypoplastic left atrium and the interatrial
right ventricle or right ventricular heave. Second sound is communication should be evaluated for restrictive flow from
often loud or may be single. Subjects with pulmonary stenosis the left atrium to right atrium.
have long ejection systolic murmurs along the left sternal Another determination to make is the looping of the
border. Continuous murmur, related to high-velocity flow ventricular mass. While d-looping is noted in majority of
across the restrictive atrial septal defect, may be heard in some hearts with this defect, l-looping of the ventricles have
patients.9,21 Otherwise, there is no characteristic murmur been reported in approximately 20 percent of cases.18 In
noted. Signs of congestive heart failure are evident in most the presence of l-loop, the left AV valve atresia, of course,
patients without associated PS. However, if there is severe represents a tricuspid valve atresia with morphologic RV
restriction of atrial septal communication, signs of pulmonary underneath the left AV valve; however, the physiology is that
edema may be seen instead. of mitral atresia.
Adequacy of atrial septal communication is assessed using
INVESTIGATIONS three criteria:
1. Diameter of the atrial level communication in 2-dimensional
image (Figures 1C and 2B).
Chest X-ray
2. Mean Doppler gradient using pulse and or continuous
Chest X-ray findings are nonspecific and reflect the combined wave signal.
effect of associated heart defects and status of pulmonary 3. Color Doppler signal (Figure 2A).
blood flow. Cardiomegaly, with globular enlargement of the Mean Doppler gradient will depend on size of the
heart is usually seen. Increased pulmonary vascular markings communication and the amount of pulmonary blood
are seen in subjects with increased pulmonary blood flow, flow at the time of evaluation. Apart from evaluating the
while the pulmonary vascular markings are diminished in adequacy of atrial level shunt initially, this should be
patients with pulmonary oligemia. In the presence obstruction performed at every follow-up study as well as after balloon
460 at the level of interatrial septum signs of pulmonary edema/ atrial septostomy or surgical septectomy since the atrial
venous congestion may be noted. communication may become inadequate over time.23
32
Mitral Atresia
A B
C D
Figures 1A to D: Selected video frames from an echocardiographic study of an infant with mitral atresia demonstrating atretic mitral valve
(AMV), indicated by arrows, in precordial long-axis view. A. and subcostal views; B, C and D. Closed C and open D tricuspid valve leaflets are
shown by arrows. Ventricular septal defect (VSD) in A and a very small atrial septal defect (ASD) in B is also shown. LA = Left atrium; RA = Right
atrium
The number (one or two), size and function of the these babies is to relieve left atrial hypertension in cases of
ventricle(s), size of the VSD, great artery origins and relation- restrictive patent foramen ovale or atrial septal defect by
ship and presence of stenosis or atresia of the pulmonary valve balloon atrial septostomy, blade septostomy, static balloon
may be determined in multiple views in a conventional man- dilatation of the atrial septum or stent placement. These
ner; apical four-chamber and subcostal views are most helpful interventions will be discussed below under management
in this regard. Suprasternal notch views should be scrutinized section. Also, cardiac catheterization is indicated prior to
along with Doppler interrogation to confirm or exclude aortic bidirectional Glenn and Fontan surgeries that these patients
coarctation. will eventually require.
When cardiac catheterization is performed, left-to-right
Cardiac Catheterization and Selective Cineangiography shunt at right atrial level is demonstrated and the oxygen
saturations in the RV, aorta and pulmonary artery are similar.
The diagnosis and assessment of associated defects can often Systemic arterial desaturation is always present and is
be made by good quality echocardiographic studies and cardiac proportional to the degree of RV outflow tract obstruction.
catheterization and angiography are rarely needed solely for Pressure pullbacks across the atrial septum should be 461
diagnostic purposes. The main reason for catheterization in performed to ensure adequacy of the atrial septal defect.
http://vip.persianss.ir
6
Congenital Valvar Lesions
A B
Figures 2A and B: Selected video frames from subcostal views of an echocardiographic study of an infant with mitral atresia indicating a small
and restrictive atrial septal defect (ASD; arrow) in A. In B, color flow mapping of the same site shows color acceleration (arrow) across this area.
LA = Left atrium; RA = Right atrium
A mean pressure gradient in excess of 5 mm Hg is considered study from Brazil which was published in 1991,24 reporting
significant, requiring intervention. The ventricular pressures outcome of a cohort of 23 patients, five babies died at ages
are at systemic level without any gradient across the aortic ranging from 11 days to 12 months, before any surgical
valve. Pressure gradient across the pulmonary outflow tract therapy could be undertaken. Remaining 18 patients (11 had
is present in patients with significant valvar or subvalvar congestive heart failure and 7 had cyanosis due to pulmonary
pulmonary stenosis. The pulmonary artery pressures are high stenosis) underwent palliative surgical procedures involving
and are at systemic level in patients with no pulmonary outflow surgical atrial septectomy, pulmonary artery banding or
tract obstruction, but are normal or decreased in subjects with Blalock-Taussig shunt. Twelve (66%) of the 18 patients
pulmonary stenosis. Pressure pullback recording across the were alive at follow-up that ranged from 1 to 57 months.
aortic arch may show pressure gradient in the descending Causes of death included heart failure (n = 1), cyanosis
aorta in cases with aortic coarctation. (n = 3) and septicemia (n = 1). One patient has had Fontan
Injection of contrast material into the left atrium may operation at the age of 10 years. Eleven of the 12 patients
provide some clarity in the mitral atresia diagnosis (Figures were in New York Heart Association functional class I and
3 and 4). Selective cineangiography in the ventricle(s), aorta are awaiting further surgical procedures. Given the recent
and pulmonary artery are likely to define the associated developments in diagnosis and treatment of the neonate with
cardiac defects. congenital heart defects, the current prognosis is likely to be
lot better than reported in the above two studies.
NATURAL HISTORY
MANAGEMENT
In the clinical/pathologic review of 52 cases by Watson et al
in 1960,3 two were stillborn and 23 babies died during the Management is dictated by the clinical presentation. The
462 neonatal period. Average survival was 6 months. Only five severity of cyanosis and level of oxygen saturation in
babies (10%) lived up to 1 year or more.3 In a more recent the newborn are largely dependent upon the severity of
32
Management at the Time of Initial Presentation
Mitral Atresia
Initial management of these babies is similar that used in
other cyanotic neonates.25 The infant’s temperature should
be monitored and neutral thermal environment maintained.
Ambient oxygen should be administered, if the infant is
hypoxemic. In cyanotic CHD patients including mitral
atresia, no more than 0.4 fraction of inspired oxygen (FiO2)
is necessary; higher levels of O2 do not increase O2 saturation
because of fixed intracardiac right-to-left shunting. In the
infants suspected of having pulmonary atresia or severe
stenosis, prostaglandin infusion (Prostaglandin E1 at a dose of
0.05–0.1 µg per kilogram of body weight per minute) to open or
maintain patent ductus arteriosus should be promptly started.
Metabolic acidosis, defined as pH < 7.25 should be corrected
with sodium bicarbonate (usually 1–2 mEq/kg diluted half
and half with 5 or 10% dextrose solution) immediately. In
the presence of respiratory acidosis, appropriate suctioning,
Figure 3: Selected cine frames from a left atrial (LA) angiogram in intubation and assisted ventilation should be undertaken.
a left axial oblique (30° LAO and 30° cranial) view demonstrating Since hypoglycemia can be a significant problem, the infant’s
atretic mitral valve (AMV). Note the opacification of the coronary sinus
(CS) via a connecting (C) vein. Such communications have been
serum glucose should be monitored. The neonates should
documented in the literature routinely receive 10 percent dextrose in water intravenously. If
hypoglycemia (< 30 mg/100 ml) is detected, 15 to 20 percent
dextrose solution should be infused. Calcium levels should
also be monitored and if hypocalcemia is detected, it should
be treated. Correction of hypovolemia and hypotension when
present should also be promptly instituted. Echocardiogram
should be performed at the earliest opportunity to establish a
complete diagnosis.
After initial stabilization of the baby, the management
depends upon the physiologic abnormality that the defect
complex produces.
Interatrial Obstruction
If there is a restrictive atrial level shunt, balloon atrial
septostomy may be urgently necessary. This may be accom
plished either by Rashkind balloon atrial septostomy26 in a
newborn or blade septostomy in an older infant.27,28 Since,
the left atrium is small and hypoplastic in the majority of
these infants, it may pose technical problems for balloon
and blade atrial septostomy.29 Static balloon dilatation of
Figure 4: Selected cine frames from a left atrial (LA) angiogram in the atrial septum30,31 with a balloon angioplasty catheter
a left axial oblique (30° LAO and 30° cranial) demonstrating atretic (Figures 5A and B) may be used which may not only relieve
mitral valve (AMV) in a patient who had previously undergone surgical the obstruction, but also keep some restriction such that there
atrial septectomy. Note the restrictive opening (two small arrows) and is no rapid fall in the pulmonary vascular resistance. Static
dilated pulmonary veins (PV). RA = Right atrium
balloon dilatation is preferred by the authors.
In some patients, the atrial septum may be intact or have
a tight patent foramen ovale, which may not even allow
pulmonary stenosis or atresia, adequacy of pulmonary blood passage of a catheter. In such situations, puncture of the atrial
flow determined by pulmonary outflow tract obstruction, size septum by Ross technique32 or radiofrequency perforation of
of patent ductus arteriosus, pulmonary vascular resistance and the atrial septum33-35 followed by static balloon atrial septal
degree of restriction at the atrial level shunt. dilatation30,31 or stent (Figures 6 and 7) implantation29,36-38 463
http://vip.persianss.ir
6
Congenital Valvar Lesions
A B
Figures 5A and B: Selected cineradiographic frames while performing static balloon dilatation of a markedly restrictive patent foramen ovale
demonstrating waisting (arrow) of the balloon. A. During the initial phases of balloon inflation which was completely abolished (B) at the conclusion
of balloon dilatation
may become necessary. These transcatheter methods may not of these patients will go into congestive cardiac failure and
be feasible or successful in some infants and surgical atrial this should be treated with adequate anticongestive measures.
septectomy is needed. Open atrial septectomy is considered As soon as a reasonable control of congestive heart failure is
more appropriate than the closed, Blalock-Hanlon atrial achieved, pulmonary artery banding should be performed to
septectomy.18,20,39 attain better control of heart failure, to prevent development
There is evidence that atrial level opening that is adequate of pulmonary vascular obstructive disease and to reduce
early in the neonatal period may become restrictive with time. It pulmonary artery pressures to near normal level.
is suggested that all babies with this condition undergo balloon
atrial septostomy performed, if they have cardiac catheterization Decreased Pulmonary Blood Flow
prior to 1 month of age. In babies who did not require early
atrial septostomy or septectomy, serial echocardiograms should In the subgroup of patients with decreased pulmonary blood
be performed to assess adequacy of atrial septal defect. Atrial flow, placement of systemic-pulmonary artery shunt40,41
septostomy or septectomy may be required later–especially along with ligation of patent ductus arteriosus may become
in the group with unrestricted pulmonary blood flow or after necessary. This is required in all babies with pulmonary
systemic-pulmonary artery shunt.18 atresia and in some babies with pulmonary stenosis.
Increased Pulmonary Blood Flow with Increased Pulmonary Blood Flow along
or without Heart Failure with Interatrial Obstruction
As the transition occurs from fetal circulation in patients This combination can occur frequently.20 We have demon-
464 without pulmonary stenosis or atresia, pulmonary blood flow strated that rapid and predictable fall in pulmonary vascular
increases as the pulmonary vascular resistance drops. Some resistance occurs in patients who undergo relief of restrictive
32
Mitral Atresia
A B
C D
Figures 6A to D: Selected cineradiographic frames while implanting the stent across a markedly restrictive patent foramen ovale demonstrating
the position of the stent prior. A. During with a waist (W) of the balloon; B and at the conclusion C of stent implantation. Note the position of the
fully inflated stent (FI) before C and after D removal of the balloon
atrial level shunt by balloon or surgical atrial septostomy.20 followed by Fontan operation.44-46 Details of these surgical
Pulmonary artery band for such patients will prevent heart palliative procedures for single ventricle repair are discussed
failure and development of pulmonary vascular obstructive in chapters on Tricuspid Atresia (Chapter 28) and Hypoplastic
disease and should be performed at the time of relieving atrial Left Heart Syndrome (Chapter 47) and will not be reviewed
septal obstruction. here.
http://vip.persianss.ir
6
Congenital Valvar Lesions
A B
Figures 7A and B: Selected video frames from subcostal views of an echocardiographic study of an infant with mitral atresia who had a stent
implanted one day (Figure 6) prior to the study, demonstrating the position of the stent (arrow) across the atrial septum. A. With color flow
mapping; B. Laminar flow (arrow) within the stent. LA = Left atrium; RA = Right atrium
band if there is unrestricted pulmonary blood flow become 4. Abbott ME. Atlas of congenital cardiac disease. American
main components of early palliative management. Systemic Heart Association, New York, NY; 1936. p. 50.
to pulmonary arterial shunt may be necessary for patients with 5. Edwards JE. Congenital mitral atresia: In Gould S (Ed).
Pathology of the heart. Thomas, Springfield, MO. 1953. p. 386.
pulmonary atresia or severe pulmonary stenosis. As the babies
6. Anderson RH, Thiene G. The clinical morphology of mitral
grow, close attention should be paid to evaluate adequacy atresia. Atresia of the left atrioventricular valve. G Ital Cardio.
of atrial septal defect by serial echocardiograms. Atrial 1981;11:1860.
septostomy or septectomy may be necessary later in infancy, 7. Rao PS. Is the term “tricuspid atresia” appropriate? (Editorial).
if it were not required or not performed in the neonatal period. Am J Cardio. 1990;66:1251.
Therefore, recognizing this constellation of cardiac defects 8. Rao PS. A unified classification of tricuspid atresia. Am Heart
helps to guide early management decisions. Later 'corrective' J. 1980;99:799.
surgical therapy consists of bidirectional Glenn and Fontan 9. Keith JD. Congenital mitral atresia. In: Keith JD, Rowe
operations, similar to other single ventricle lesions. RD, Lad P (Eds). Heart Disease in Infancy and Childhood
Macmillan: 3rd edition. New York; 1977. pp. 549.
10. Rao PS. Atrioventricular canal mimicking tricuspid atresia:
When health is absent, wisdom cannot reveal itself, art echocardiographic and angiographic features. Br Heart J.
cannot manifest, strength cannot fight, wealth becomes 1987;58:409.
useless, and intelligence cannot be applied. 11. Edwards JT, Rodgers HM. Atresia of the orifice of the mitral
—Herophilus valve. J Tech Methods. 1947;27:62.
12. Edwards JE, Dushanbe JW. Thoracic venous anomalies: 1
REFERENCES Vascular connection of the left atrium and left innominate
vein (levo atrio-cardinal vein) associated with mitral atresia
1. Thiene G, Daliento L, Frescura C, et al. Atresia of left atrio in premature closure of the patent foramen ovale. Arch Path.
ventricular valve. Anatomic investigation in 62 cases. Br Heart 1950;49:517.
J. 1981;45:393. 13. Hollman A. Electrocardiographic diagnosis of right ventricular
2. Norwood WI, Kirklin JK, Sanders SP. Hypoplastic left heart hypertrophy in infancy and childhood. Br Heart J. 1958;20:129.
syndrome: experience with palliative surgery. Am J Cardio. 14. Lucas RV Jr, Lester RG, Lillehei CW, et al. Mitral atresia with
1980;45:87. levoatriocardinal vein. A form of congenital pulmonary venous
3. Watson DG, Rowe RD, Conen PE, Duckworth JW. Mitral obstruction. Am J Cardiol. 1962;9:607.
atresia with normal aortic valve. Report of 11 cases and review 15. Lee ML, Wang JK, Lue HC. Levoatriocardinal vein in mitral
of literature. Pediatrics. 1960;25:450. atresia mimicking obstructive total anomalous pulmonary
466 venous connection. Int J Cardiol. 1994;47:1.
32
16. Eliot RS, Shone JD, Kanjuh VI, et al. Mitral atresia. A study of 33. Justino H, Benson LN, Nykanen DG. Transcatheter creation
32 cases. Am Heart J. 1965;70:6. of an atrial septal defect using radiofrequency perforation.
Mitral Atresia
17. Moreno F, Quero M, Diaz LP. Mitral atresia with normal aortic Catheter Cardiovasc Intervent. 2001;54:83.
valve: A study of eighteen cases and a review of the literature. 34. Sakata Y, Feldman T. Transcatheter creation of atrial septal
Circulation. 1976;53:1004. perforation using a radiofrequency transseptal system: novel
18. Mickell JJ, Mathews RA, Park SC, et al. Left atrioventricular approach as an alternative to transseptal needle puncture.
valve atresia: Clinical management. Circulation. 1980;61:123. Catheter Cardiovasc Intervent. 2005;64:327.
19. Rao PS. Tricuspid Atresia. eMedicine from WebMD. Updated 35. Hill SL, Mizelle KM, Vellucci SM, et al. Radiofrequency
February 09, 2009. Available at: http://www.emedicine.com/ perforation and cutting balloon septoplasty of intact atrial
ped/topic2550.htm. septum in a newborn with hypoplastic left heart syndrome
20. Rao PS, Kulangara RJ, Moore HV, et al. Syndrome of using transesophageal ICE probe guidance. Cath Cardiovasc
single ventricle without pulmonary stenosis but with left Interv. 2005;64:214.
atrioventricular vale atresia and interatrial obstruction. J 36. Gewillig D, Boshoff L, Mertens L. Creation with a stent of
Thorac Cardiovasc Surg. 1981;81:127. an unrestrictive lasting atrial communication, Cardiol Young.
21. Ross J Jr, Braunwald E, Mason DT, et al. Interatrial communica 2002;12:404.
tion and left atrial hypertension: a cause of continuous murmur. 37. Eicken H, Gildein C, Schreiber C, et al. Stenting of a restrictive
Circulation. 1963;28:853. foramen ovale in a patient with hypoplastic left heart syndrome.
22. Magherini A, Azzolina G, Careri J. Anatomy of the echocardio Internat J Cardiol. 2006;113:254A.
graphic crux cordis in the evaluation of the spectrum of 38. Holzer RJ, Wood A, Chisolm JL, et al. Atrial septal inter
atrioventricular valve atresia. Int J Cardiol. 1984;5:163. ventions in patients with hypoplastic left heart syndrome. Cath
23. Perry SB, Lang P, Keane JF, et al. Creation and maintenance of Cardiovasc Interv. 2008;72:696.
an adequate interatrial communication in left atrioventricular 39. Weldon CS. Classics in thoracic surgery: The Blalock-Hanlon
valve atresia or stenosis. Am J Cardiol. 1986;58:622. operation. Ann Thorac Surg. 1987;43:448.
24. Atik E, Ikari NM, Aiello VD, et al. Atresia of the left 40. Blalock A, Taussig HB. The surgical treatment of malformations
atrioventricular valve with patency of the aorta: anatomico- of the heart in which there is pulmonary stenosis or atresia. J
functional analysis of 23 patients. Int J Cardiol. 1991;32:281. Am Med Assoc. 1945;128:189.
25. Rao PS. Principles of management of the neonate with 41. de Leval MR, McKay R, Jones M, et al. Modified Blalock-
congenital heart disease. Neonatology Today. 2007;2(8):1. Taussig shunt. Use of subclavian artery orifice as flow regulator
26. Rashkind WJ, Miller WW. Creation of an atrial septal defect in prosthetic systemic-pulmonary artery shunts. J Thorac
without thoracotomy: Palliative approach to complete transpo- Cardiovasc Surg. 1981;81:112.
sition of the great arteries. J Am Med Assoc. 1966;196:991. 42. Pridjian AK, Mendelsohn AM, Lupinetti FM, et al. Usefulness
27. Park SC, Zubebuhler JR, Neches WH, et al. A new atrial of the bidirectional Glenn procedure as staged reconstruction
septostomy technique. Cath Cardiovasc Diagn. 1975;1:195. for the functional single ventricle. Am J Cardiol. 1993;71:959.
28. Park SC, Neches WH, Zuberbuhler JR, et al. Clinical use of 43. Tanoue Y, Sese A, Ueno Y, et al. Bidirectional Glenn procedure
blade atrial septostomy. Circulation. 1978;58:600. improves the mechanical efficiency of a total cavopulmonary
29. Rao PS. Role of Interventional Cardiology In Neonates: connection in high-risk Fontan candidates. Circulation.
Part I. Non-Surgical Atrial Septostomy. Neonatology Today. 2001;103:2176.
2007;2:9. 44. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax.
30. Shrivastava S, Radhakrishnan S, Dev V, et al. Balloon dilatation 1971;26:240.
of atrial septum in complete transposition of great arteries—a 45. Kreutzer G, Bono H, Galindez E, et al. Una operacion para
new technique. Indian Heart J. 1987;39:298. la correccion de la atresia tricuspidea. Ninth Argentinean
31. Rao PS. Static balloon dilation of atrial septum (Editorial). Am Congress of Cardiology, Buenos Aires, Argentina, Oct. 31-
Heart J. 1993;125:1826. Nov. 6, 1971.
32. Atz AM, Feinstein JA, Jonas RA, et al. Preoperative mana 46. de Laval MR, Kilner P, Gewilling M, et al. Total cavopulmonary
gement of pulmonary venous hypertension in hypoplastic connection: a logical alternative to atriopulmonary connection
left heart syndrome with restrictive atrial septal defect. Am J for complex Fontan operation. J Thorac Cardiovasc Surg.
Cardiol. 1999;83:1224. 1988;96:682.
467
http://vip.persianss.ir
c hapter
IntroductIon and the left ventricular outflow tract (LVOT). The theory
of hemodynamic moulding postulates that the failure of
The aortic valve (AV) is one of the semilunar valves of the development of cardiac structures is caused by diminished
heart, normally located at the left ventriculoarterial junction. blood flow through them. In fact, restrictive foramen ovale,
It has a critical role in maintaining the fine coordination of left ventricle, hypoplastic left ventricle (LV) and abnormal
fluid mechanics between the systemic ventricle and systemic mitral valve are often seen in association with aortic stenosis/
arterial system during the entire cardiac cycle. Inherently, it is atresia and coarctation or interruption of arch.1,9-15
tricuspid, i.e. guarded by three leaflets. However, occasionally We will see later in the chapter that the AV forms an
the number of leaflets differs, leading to a restrictive or important boundary of the LVOT and has a complex
regurgitant valve.1,2 These numerical variations were known relationship with membranous and muscular interventricular
in ancient era. In fact, Major Leonardo da Vinci was one of septum and with both the mitral leaflets. Any embryological
the first to call attention to the aortic valve with two leaflets.3 malformation of these structures carry a composite anatomical
and therapeutic implications.16
Prevalence
genetIcs and FamIlIal InherItance1-4,14,17,18
The bicuspid aortic valve (BAV) is the most common abnor-
mality of the aortic valve. It has an incidence of 0.03 to 0.34 There are compelling evidences of the familial occurrence of
per 1,000 live births and constitutes about 7 percent of all con- aortic stenosis. It is known to occur with Turner syndrome
genital cardiac malformations. The prevalence of congenital and Jacobsen syndrome. Non-syndromic occurrence occurs
BAV is 1.3 percent. Of that 2 percent patients will experience sporadically following the pattern of multifactorial inheri-
significant aortic stenosis or regurgitation by adolescence.1,4-9 tance. However, the male predominance (male-to-female
ratio ≥ 3:1) as well as association of BAV with Turner’s
embryology10–16 syndrome (45X chromosomal pattern) suggests an X-linked
etiology. A heritability study found no X-linkage but did find
The embryonic truncus arteriosus is divided by the spiral linkage to chromosomal regions 5q, 13q, and 18q. Mutations
conotruncal septum. The normal right and left aortic leaflets in the NOTCH1 gene (chromosome 9q) leads to signaling
form at the junction of the ventricular and arterial ends of the abnormalities that may be responsible for the development
conotruncal channel. The non-septal leaflet (posterior) cusp of a bileaflet aortic valve. Ellison et al studied an extended
normally forms from additional conotruncal channel tissue. family with BAV and found no evidence of linkage of BAV
The conotruncal channel tissue is subendocardial and needs in their pedigree to either the NOTCH1 gene or to the
to undergo the process of cavitation and hollowing to form chromosome 15 locus. They concluded that the disorder in
the leaflets. In the 5th week of embryological development, this family might be caused by a gene at a novel locus.13
excess mesenchymatous tissue is absorbed to form an outline Although aorta in patients with BAV have histopathological
of the aortic valve at the apex of the aortic vestibule. The findings similar to aorta in Marfan syndrome the underlying
aortic valve cusps and sinuses are well formed by the 8th genetic abnormality of Marfan syndrome, mutation in the
week. The failure of any of the developmental steps leads FBN1 gene that encodes fibrillin-1 and is not found with
to isolated or combined malformation of the aortic valve BAV disease.
aortIc root: anatomIcal and FunctIonal asPects 33
definition of the aortic root
Figure 1: Aortic root—attachment of the leaflets and interleaflet Aortic Annulus 469
fibrous triangles. LC = Left coronary ostium; LCC = Left coronary
cusp; NCC = Non-coronary cusp; RC = Right coronary ostium; RCC The aortic annulus is a 3-pronged crown-like ring and has a
= Right coronary cusp. base formed by aortic annulus, a top formed by sinotubular
http://vip.persianss.ir
6 Sinotubular Junction—The Outlet of the Aortic Root
The STJ is the junction between the aortic root and ascending
congenitAl VAlVAr lesions
aorta. It contains the sinus ridge and the sites of the attachment
of the peripheral zones of apposition between the aortic valve
leaflets.
The diameter of the aortic root at the level of the sinotubular
junction is 10 to 15 percent less than that at the level of
ventriculoaortic junction.14-20
http://vip.persianss.ir
6 chamber for the low pressure pulmonary venous system. needs a constant diastolic pressure to maintain the mean
To achieve this lowest pressure, the ventricle needs active systemic blood pressures, so as to maintain the physiological
relaxation, a process, which requires energy. This active requirement of the peripheral tissues as well as to maintain the
congenitAl VAlVAr lesions
relaxation creates a suction effect, which helps in the early coronary blood flow during the diastole. The incompetent AV
rapid filling phase of diastole. The atrial systole provides hinders these physiological necessities.
atrial kick and the remaining left atrial blood is pushed
forward into the LV. To understand the mechanics of the relatIonshIPs oF the aortIc root and Its
ventricle one must understand the concept of ‘preload’ and clInIcal ImPortance
‘afterload.’ Often these terms create a lot of confusion.
Preload can be defined as all of the factors that contribute to
the passive ventricular wall stress (or tension) at the end of
aortic root and left ventricular outflow tract
diastole, and the term afterload can be defined as all of the The left ventricular outflow is a small area. This subaortic
factors that contribute to the total myocardial wall stress (or area, also known as aortic vestibule, is smaller and less
tension) during systolic ejection. The preload refers to the well defined than right ventricular outflow tract (RVOT).
stretch of the LV just before the onset of contraction. The Anteriorly, it is formed by the muscular and membranous
inflow of the atrial blood contributes to the preload of the ventricular septum. The posterior boundary is drawn mostly
ventricle. During ejection phase, the aortic pressure almost by the free inferior margin of the anterior mitral leaflet that
equalizes to LV and little gradient exists. The blood flows forms a curtain between the inflow and the outflow of the LV.
unobstructed to the peripheral tissues.14,15,28-30 Also, a small part of the posterior boundary is contributed by
Physiologically, during each cardiac cycle, the aortic root the intervalvar septum and the posterior mitral leaflet where
varies in symmetry and dimensions. Geometrically, aortic it fuses with the AML.14-17
root dimensions differed approximately by 12 percent during
the cardiac cycle in animal experiments. Recently, Heer et al relationship of the right and left ventricular outflow
demonstrated the significant individual dynamic changes in tracts to the aortic root
the dimensions of the aortic root in a study utilizing ECG-
gated multidetector computed tomography.30 Despite the fact that RVOT and LVOT have significant difference
The model of the aortic root was studied for its inherent in length, at the base of the heart, aortic and pulmonary valve
capacity to effectively withstand prolonged sheering forces can be seen almost at the same plane (Figures 5 and 6). This
generated during the extreme change in pressures on either is possible because the RVOT wraps circumferentially around
side of the AV. Now it is known, that various anatomical the LVOT. Therefore, the anterior wall of the LVOT shares
asymmetries customary at the level of the cusps give part of the posterior wall of the RVOT. This sharing of the
mechanical advantage to the aortic root during the cardiac common wall exists beyond the semilunar valves. The main
cycle. Dagum et al published their experimental work in a pulmonary artery (MPA) and the proximal right pulmonary
three-dimentional model of the bovine aortic root on how artery, share their walls with the proximal ascending aorta.
it undergoes complex, asymmetric deformations during Echocardiographically, this arrangement is described as ‘cup
the various phases of the cardiac cycle. The description and saucer’ appearance seen in parasternal short-axis or basal
included strain happening at the aorto-ventricular and STJ, view, where the AV can be seen as a circle or cup. The right
as well as the elongation, compression, sheer and torsional and left atrium forms the posterior part of the saucer and the
deformation of the aortic root.30 These deformations were not tricuspid valve, RVOT, PV and MPA, all opening up in the
homogeneous among the left, right, and non-coronary regions. long-axis in this view, form the anterior and the lateral part. The
Furthermore, changes in the left ventricular volume, pressure, PV lies to the left and anterior to the AV. As described above,
and contractility affected the degree of deformation in a non- the AV is in fibrous continuity with the AML.13,14,16,30
uniform manner in the three regions studied and these effects
varied during isovolumic contraction, ejection, isovolumic aortic root and membranous septum
relaxation and diastole.13,14,28-30
They concluded that the aortic valve repair techniques or The membranous interventricular septum is morphologically
methods of replacement using unstented autograft, allograft, an important area. Posteroinferiorly, it is related with the
or xenograft tissue valves that best preserve this normal tricuspid valve. The anterosuperior boundary is formed by the
pattern of aortic root dynamics should translate into a lower AV (Figure 7). On the left side due to the higher attachment of
risk of long-term cusp deterioration.30A the mitral leaflet, the membranous septum is atrioventricular
Obstructive lesions of the aortic valve manifest as systolic and a defect in this area presents with a obligatory LV to RA
gradient between LV and aorta which in turn, increases the shunt. Due to this important relationship, the anatomy of this
left ventricular afterload. On the contrary, ineffective closure area has enormous therapeutic importance. A septal defect in
472 of the AV exposes the aorta to the ventricular diastolic low this area may be complicated by aortic valve prolapse and
pressure and promotes reverse flow across the AV. The aorta may cause an incompetent valve.
33
A B
Figures 6A and B: A. Aortic valve sharing place and fibrous ring with mitral valve (MV) and tricuspid valve (TV). The non-coronary cup is in close
contact with fibrous ring, with permission14; B. 3D echocardiography showing wedged position of aortic valve between mitral and tricuspid valve.
AV = Aortic valve; MV = Mitral valve; PV = Pulmonary valve; TV = Tricuspid valve. Image courtesy: Dr Nagendra Chauhan
473
http://vip.persianss.ir
6
congenitAl VAlVAr lesions
474
33
central PosItIon oF the aortIc root and Its can interfere with the competency of the valve and can
ImPlIcatIons In InterventIons culminate into the valve replacement procedure, in the long
run. The understanding of the aortic root and its dimensional
The aortic root and its adjacent cardiac structures are subject of variation at different levels are significant. The sizing of the
immense clinical interest because many surgical and catheter aortic annulus at hinge points in 2D echocardiogram has to
interventions are performed, in this vicinity, to restore the be precise for the optimum choice of balloon.9,36
normal and natural functioning of the diseased heart. There
can be two kinds of cardiac interventions: when manipulation is in the adjacent structures:
1. When the aortic root and aortic valve are directly cardiac catheter and surgical Interventions37
manipulated.
2. When interventional manipulation is in the adjacent Many catheter interventions, like device closure of atrial septal
structures where the aortic root is used as a passage or to defect (ASD), VSD, aortopulmonary window, ruptured sinus
anchor the artificial material. of Valsalva or paravalvular leaks take place in or around the
aortic root. For example, in the device closure of ASD, wrong
when the aortic root and aortic valve are choice or placement of device may lead to aortic perforation.37
directly manipulated A wrongly placed device for perimembranous VSD can lead to
deformation of the aortic cusp. Surgical complications can also
The aortic root and its components are continuously working happen in the form of perforation or valvar dysfunction.38 Both
under high pressures and the resulting shear forces. There may types of interventions may cause conduction abnormalities.
be inherent problems like numerical cuspal abnormalities or
abnormalities of the aortic root wall. Moreover, the functional dIseases oF the aortIc valve
abilities of the aortic root may also decline due to the neonatal
or infantile surgical procedures like arterial switch, Ross As mentioned above there are two typical processes that can
procedures or adult aortic root reconstruction.14,15,17,34,35 affect the aortic valve. One is aortic stenosis in which the
As we have learned that the aortic root has a mechanism valve fails to open fully, thereby obstructing blood flow from
to make it physiologically effective in the presence of shear the heart and the second is aortic valve insufficiency, causing
forces, it is clear that all interventional methods are yet to be increased LV preload due to regurgitation of blood from
differential to this innate ability. This may be the explanation aorta to LV during diastole. These two conditions frequently
for the relatively rapid deterioration of the artificial material coexist. Besides, pathological aortic root dilatation is also
in the aortic position. These facts must be considered, while seen frequently, in bicuspid valve disease.22-24,39-48
choosing the interventional steps and prosthesis. Common causes of aortic stenosis include rheumatic fever,
The ballooning procedures are less interfering with degenerative calcification and congenital diseases such as
the natural functional abilities of the aortic root. But they BAV (Table 2).22-24,39-46,48 The spectrum of congenital aortic 475
http://vip.persianss.ir
6
table 2 morphology of stenotic aortic valve
Causes of aortic stenosis
Routinely, morphology of the AV is evaluated on echo-
congenitAl VAlVAr lesions
Congenital Abnormal number of cusps—unicuspid, cardiography. The parasternal views (short-axis view at the
bicuspid, tricuspid, quadricuspid, six-cuspid
base of the heart and long-axis view) are used to determine
Calcific or degenerative the morphology and number of cusps. Subcostal coronal view
Rheumatic valve disease with anterior tilt, apical four-chamber with anterior tilt and
Other conditions: Homogenous type II hyperlipoproteinemia parasternal long-axis views are particularly useful to define
Metabolic (Fabry’s disease) the valve motion.17,22,23,41
Systemic lupus erythematosus Normal AV is tricuspid and has three leaflets of nearly
Alkaptonuria equal size. Three commissures form a Y-shaped pattern
in diastole. In systole, the leaflets open along these
commissures to create a wide, open triangular orifice
stenosis (AS) ranges from mild AS to a severe form of the (Figures 10A). The congenital anomalies of AV comprise
disease, which may manifest in fetal life and terminates into a spectrum of deformities, which includes abnormal form,
hypoplastic left heart. size and the number of leaflets (Table 3).22-24,39-46,48 Normal
The aortic root and aortic valve may have morphological AV leaflets are thin and have unrestricted mobility. In
and positional abnormalities, as is shown in Table1. stenotic valves, leaflets are thickened and domed in systole.
Common causes of aortic regurgitation (AR) include Doming of valve leaflets during systole occur due to limited
dilation of the aorta, infective endocarditis, myxomatous cusps separation leading to restricted mobility of valve
degeneration of the AV and Marfan syndrome.22,23,38-43 cusps.14,15,17,22-24,38-43,46
valvar aortIc stenosIs The Unicuspid Aortic Valve (Figures 11 and 12)
Valvar AS is the most common type of LVOT hindrance, A unicuspid valve can be of two pathological varieties—
accounting for 70 to 91 percent of aortic obstructions. It is acommissural and unicommissural and can be seen in SAX
caused by cusp deformities with or without narrowing of view. The acommissural valve is a rare anomaly and has a
the ‘annulus’. It may manifest early, in a neonate or later in single membrane-like leaflet with a central circular orifice.
infants and children due to the progressive obstruction of the Unicommissural unicuspid valves occur more frequently and
inherently abnormal valve.22,23,38-43 are the most common cause of symptomatic AS in neonates.
The evaluation of valvar aortic stenosis should include: The orifice is typically eccentric and circular in systole
a. Morphology of the stenotic valve (Figures 11 and 12). In diastole, an eccentrically located
b. Dimensions of the aortic root valve closure is seen with no raphae. The unicuspid valve is
c. Severity of valvar obstruction generally stenotic in neonatal period though occasionally it
d. Left ventricular function has sufficient redundancy and may be the cause of obstruction
e. Associated anomalies. in adult life.22,23,46
A B
476 Figures 10A and B: A. Centrally placed tricuspid aortic valve (Mercedes-Benz sign); B. Centrally placed bicuspid aortic valve.
LV = Left ventricle; RA = Right atrium; RV = Right ventricle
table 3 parasternal short-axis view. Additional short axis features that 33
Morphology of the valve support the diagnosis, include leaflet redundancy, infolding
and eccentric valve closure. In parasternal long-axis view,
A B c
477
Figures 12 A to c: Unicuspid unicommissural aortic valve: A. Opened out ascending aorta showing a unicuspid aortic valve with severe
stenosis of its orifice in a pathological specimen. Arrow points to the single true commissure; B. Enface view on transthoracic echo; C. Computed
tomography angiography. Image courtesy (12A): Dr Pradeep Vaideeshwar
http://vip.persianss.ir
6
congenitAl VAlVAr lesions
A B
c D e
Figures 13A to e: Bicuspid aortic valve: A. Morphology; B. Echocardiography in short axis showing the closed valve; C. Open valve; D. Excised
aortic valve (AV) in a case of aortic stenosis showing slightly unequal calcified semilunar cusps. Note raphae (arrow) in the larger cusp; E.
58 years male with ischemic heart disease showed bicuspid AV. Note atheromatous narrowing of the left circumflex artery LCA. Ao = Aorta;
LMC = Left main coronary artery; LV = Left ventricle; MV = Mitral valve; RCA = Right coronary artery. Image courtesy (13D and E): Dr Pradeep
Vaideeshwar
A B
Figures 14A and B: Classification of Bicuspid aortic valve (base on refrence 47 to 49): A. By Sabet et al47; B. Roberts et al48. Rt = Right; Lt = Left
478
Congenitally Stenotic Tricuspid Aortic Valve LV mass associated with an increased relative wall thickness. 33
This is usually calculated as 2 × posterior wall thickness/LV
Congenitally stenotic tricuspid AV has three aortic cusps. The diastolic diameter and a value > 0.45 is abnormal.52
A B
Figures 15A and B: Quadricuspid aortic valve. Parasternal short axis view shows the valve. A. Closed position; B. Open position. 479
CA = Coronary artery ; LA = Left atrium; RA = Right atrium; RVOT = Right ventricular outflow tract
http://vip.persianss.ir
6
congenitAl VAlVAr lesions
A B
c D
Figures 16A to D: A. PLAX—maladaptive concentric LVH (diastole), noncompliant LV. Note the hypo-dense area (arrow ) in myocardium of
LV free wall; B. PLAX (Systole)—systolic obliteration of cavity leading to abnormal RWT (RWT-Relative wall thickness: ratio of the posterior
wall thickness plus septal thickness over LV internal dimension); C. PLAX—turbulent flow at LVOT (systolic anterior motion of MV); D. M-mode
echo—systolic anterior motion of MV. LV = Left ventricle; LVH = Left ventricular hypertrophy; LVOT = Left ventricular outflow tract; MV = Mitral
valve
d. This left ventricular hypertrophy (LVH), which is an incidental finding on echocardiographic examination or at
adaptive change is actually maladaptive and leads to autopsy. Only 2 percent of the patients with congenitally
diastolic dysfunction and abnormal coronary flow and malformed AV may experience clinically significant AS or
can add up adversely, to the overall outcome. The animal regurgitation by the adolescence.14,15,17,22,23,58,60
experiments have showed an advantage if this maladaptive Children who develop early progressive, pathologic chang-
LVH can be prevented.52 es in the BAV are more likely to develop valve regurgitation
e. In the older patient population, women have more wall than stenosis.46,48
thickness than cavity size, while men have relatively less Many patients with abnormal AV may develop endocarditis
thickening and more cavity space.52 and may present with fever or systemic embolization at early
f. The favorable role of drug therapy with statins, angiotensin or late age.56,57
converting enzyme (ACE) inhibitors and certain other drugs
on the progression of AS in adults has been studied and aortic stenosis in older children
published but there is no such study in pediatric age group.52-54
Symptoms14,17,18,58,59,60
clinical Presentation
Grown up children are generally asymptomatic during
Unicuspid valves generally present early in the neonatal age childhood. They have normal growth and development. The
group with severe AS. Usually, the results of the interventional most commonly reported symptoms are fatigability, exertional
procedures are suboptimal. BAV may be diagnosed in patients dyspnea, angina pectoris and syncope. Easy fatigability is
480 of any age. BAV may remain silent and be discovered as an the frequent symptom and has been reported in 15 percent of
patients with mild AS and 31 percent of patients with severe the rapid distention of the proximal aorta at the onset of 33
AS. Interpretation of the clinical significance of this symptom ejection. Aortic ejection clicks are usually best heard with
is difficult. In severe AS, angina or syncope are reported in less the diaphragm in the second right intercostal space or at the
http://vip.persianss.ir
6
congenitAl VAlVAr lesions
Figure 17: Phonocardiogram: (A) Normal heart sounds; (B) Aortic stenosis; (C) Aortic regurgitation
modalities. The presence of LVH with ST segment depression so called wide QRS-T angle. Various criteria for LVH in
and T wave inversion in the left precordial leads (strain respect to reference charts can be applied.60-62
pattern), though, less sensitive (< 25%) are fairly specific for In neonates and infants, there may be significant right
severe stenosis (Figure 18). The Holter monitoring of these ventricular hypertrophy (RVH) and normal left ventricular forces.
patients may help in recognizing the dysrhythmias. This is In infants having hypoplastic LV, R wave in the left precordial
important to know as there is evidence of a strong relationship leads will be smaller. Increased left ventricular forces are not seen
between ventricular arrhythmias and sudden death in patients in neonatal period. The P wave may be normal or bifid and T
with AS. waves may be inverted or flattened in lead I, aVL, V5, V6.60-62
The P wave is normal or bifid suggesting the presence of
mitral regurgitation (MR). The QRS axis may be normal. The radiology17,58,60
depolarization loop is clockwise with Q waves seen in the
inferior leads—aVF, III. LVH is represented by tall R wave Heart size is usually normal or minimally enlarged on chest
in lead II, aVF, deep S in V1, tall R waves in V5-6, deeply radiograph in children with AS. The cardiac apex may be
inverted T waves also seen pointing against the QRS complex, rounded in the frontal projection and there may be posterior
482
Figure 18: Electrocardiogram in aortic stenosis shows left ventricular hypertrophy (LVH) with left ventricular strain pattern
displacement of the cardiac silhouette in the lateral projection heart borders and often with left atrium (LA) enlargement 33
in patients with LVH (Figure 19A). Left atrial enlargement, if (Figure 19B).17,60
present, strongly suggests a severe degree of stenosis or presence
A B 483
Figures 20A and B: A. The depiction of possible type and extent of bicuspid aortic valve (BAV) associated aortic abnormalities (shown on
3D reconstructed image); B. Echocardiogram in parasternal long-axis view shows dilated aortic root in an adult with BAV. Image courtesy:
Dr Apoorva Goyal
http://vip.persianss.ir
6
congenitAl VAlVAr lesions
A B c
Figures 21A to c: Computed tomography angiography in elderly woman: A. With non-obstructed bicuspid aortic valve (BAV) showing dilated
aortic root; B. BAV with no raphae; C. With non-obstructed BAV—coarctation of aorta. Image courtesy: Dr Apoorva Goyal
right upper parasternal view and to keep the probe along the mean gradient (Figure 22A). The peak gradient is determined
long axis of the ascending aorta and marker pointing towards from the peak velocity using the modified Bernoulli equation
the neck. Angle correction should be avoided while taking (p = 4V2) and mean gradient by squaring the instantaneous
the gradients. In addition, the cursor must be kept away from velocities during the systolic ejection period.17,22,23,41
the mitral valve. A difference in timing of the systolic signals, The catheter derived peak-to-peak gradient is the accepted
may distinguish between AS and MR (Figure 22A). The MR standard used for prognosis and to plan interventions. In
signals starts during the isovolumic contraction and continue general, the Doppler measured peak gradient corresponds
throughout isovolumic relaxation. Figure 22B demonstrates to the catheter measured peak instantaneous pressure
the overshooting LV pressure tracing in the catheterization gradient, which is fundamentally different from the peak-
laboratory, suggestive of AS in a patient diagnosed on the to-peak catheter gradient. This correlation between the two
basis of high velocity signals on TTE. measurements is not nearly as close as with PV stenosis. In
some children, especially with moderate degree of stenosis,
Overestimation of the Gradient Across the AV two measurements can differ by 30 mm Hg. Mean gradients,
measured by averaging the instantaneous catheter or Doppler
The velocity determination across the AV is flow related. gradients over the systolic ejection period, correspond more
Hence, the conditions causing increased flow such as AR, closely to each other. The Doppler mean gradient has several
elevated cardiac output and heart rate, as seen in anemia, advantages over the Doppler peak instantaneous gradient:17,41
anxiety, pregnancy and exercise, will increase the flow 1. Doppler mean gradient is comparable to the mean pressure
velocity across the AV.17,18,23,41 gradient measured at the cardiac catheterization.
2. Doppler mean gradient is the average of all the peak
Underestimation of the Gradient Across the AV instantaneous gradients throughout the systole and is not
based on single peak velocity. Therefore, it can be obtained
The AV velocities recorded when cardiac output is low such with greater accuracy and reproducibility.
as in left ventricular failure associated with neonatal or elderly 3. Mean gradient is less affected by transvalvular flow.
aortic stenosis, does not represent the severity of the AS. 4. Mean gradient is the basis of calculation of valve area by
Also, underestimation of true severity can occur due to a using Gorlin equation.
non-parallel intercept angle. At higher velocities, a small error
may lead to significant underestimation of gradients because
of the quadratic relation between velocity and pressure aortIc valve area
gradient.17,18,23,41
Aortic valve area can be measured by the following
calculatIon oF the Pressure gradIent methods: 17,22,23,41
1. Planimetery: The AV area can be measured by direct
484 Transvalvar pressure gradients are usually calculated from tracing from the parasternal short-axis view at the level of
the Doppler aortic velocity profiles, the peak gradient and the the great vessels on two-dimensional echocardiography.
33
Figures 22A and B: A. Doppler aortic valve (AV) mean gradient from
apical five chamber view showing the high-velocity jet; B. Recording
of valve gradient in the cath lab. Notice the difference between left
ventricular peak and AV peak gradient (dark area). Attribution: Creative
B commons attribution/share
table 4A
table 4B
Severity of aortic stenosis17,18,23,41 Echocardiography in quantifying the severity of aortic stenosis
Mild Moderate Severe To assess the severity of AS, the following echocardiographic
criteria are used:
Peak velocity < 3.0 3.0–4.0 > 4.0
(meter/second) 1. Measurement of doppler pressure gradients17,18,23,41:
a. Peak instantaneous gradient
Mean gradient (mm Hg) < 25 25–40 > 40 b. Mean pressure gradient
2. Measurement of valve area:
Ao valve area (cm2/m2) 1.5–0.8 0.8–0.5 < 0.5
a. Direct planimetery in 2D echocardiography
AV area (cm2) 1.5 1.0–1.5 < 1.0 b. Continuity equation
c. Proximal isovelocity surface area method from color
Ao = Aorta; AV = Aortic valve Doppler
3. indirect evidence of stenosis:
a. Left ventricular mass from 2D echocardiography
b. LV mass/volume ratio 485
c. LV acceleration time and acceleration time/ejection time
ratio
http://vip.persianss.ir
6 There are some limitations in pediatric patients. Those are: procedure rather than valvotomy, even if left ventricular
a. Fast heart rate leading to limitation of frame rates volume is not critically small.65
b. Error in measurement of small orifice The critical AS presenting in neonatal period is a lethal
congenitAl VAlVAr lesions
c. Irregular valve opening that are difficult to trace. disease. Kim et al have highlighted the morphological
2. Aortic valve area by continuity equation: abnormalities found in critical AS.63 They examined the
postmortem specimen of two cases with critical AS and
CSA LVOT × VTI LVOT reported an extreme pattern of myocardial abnormalities of two
(CSA AV) =
VTI AV types, one consisted of numerous clefts of intertrabeculated
CSA = Cross sectional area of aortic valve spaces and endocardial fibroelastosis and other was
VTI = Velocity time integral suggestive of myocardial ischemic changes. These findings
AV = Aortic valve suggest that only functional and anatomical assessment is not
LVOT = Left ventricular outflow tract adequate to predict the outcome and there are more complex
morphological issues modifying the outcome.
echocardiographic evaluation of diastolic Usually, critical AS does not manifest as fetal congestive
Function of left ventricle heart failure, but has many severe hemodynamic effects leading
to additional structural malformations. In view of the fact,
Diastolic ventricular function is assessed by the filling that these fetuses have a potential for developing hypoplastic
abnormalities of the LV. From the MV inflow Doppler left heart syndrome, many centers are offering them fetal
recordings, peak flow velocities, filling-rates, proportion valvotomy, a procedure to avoid the underdevelopment of the
of flow in various phases of diastole may be assessed. left side of heart. Seemingly, these procedures are attractive
Comparative studies of these subjects with normal controls solutions to the CHDs with otherwise grave prognosis, yet
have revealed higher E velocity, a much higher A velocity, they have high procedural risk and limitations. The fetal
therefore an inverse E/A ratio. The percentage of total Doppler cardiac interventions are not allowed in India as of now.
area in the first-third of diastole was significantly lower and The routine clinical examination and tests of the neonates
the percentage of the total Doppler area under the A wave was with critical AS, usually differ from older infants and children
higher.41 and show involvement of the right heart instead of the left. This
is possible, as the two sides of the heart is directly connected
tissue doppler Imaging in aortic stenosis63 by the atrial communication as well as patent ductus. The
hepatomegaly, epigastric pulsation, right heart pulsation,
Tissue Doppler has some role in assessing the ventricular right ventricular dominance can be seen. Due to the presence
function. Bruch et al assessed 23 cases of moderate to severe of pulmonary venous hypertension and relatively small
aortic stenosis by tissue Doppler and found that in patients hypertrophied LV, radiological picture may mimic obstructed
with AS, systolic (S′) and early diastolic mitral annular total anomalous pulmonary venous connection or pneumonia.
velocities (E′) were significantly reduced in comparison to The baby may have small failing LV, obstructive mitral valve,
control subjects (systolic, 5.5 +/– 1.2 vs 8.3 +/– 1.3 cm/s; early MR, coarctation of aorta and PDA. Echocardiography will
diastolic, 5.6 +/– 1.6 vs 10.2 +/– 3.0 cm/s, P < .001 for both provide the anatomical diagnosis, but then again, Doppler based
comparisons), but ejection fraction, fractional shortening, and assessment of severity may be underestimated. The outcome of
cardiac index were normal. In patients with AS, LV pre-A aortic balloon valvuloplasty (ABV) may be suboptimal, but it
pressures (14 +/– 4 mm Hg)64 and end-diastolic pressures provides, a life saving palliation. Figures 23A and B show the
were high (19 +/– 7 mm Hg). In such patients, the mitral E/E′ changes in myocardium and papillary muscles. Figures 23A
ratio was significantly related to LV pre-A pressure (r = 0.75, to D are TTE images of a 14-hour-old neonate with hydrops
P < .001) and to LV end-diastolic pressure (r = 0.78, P < .001). fetalis on ventilator, who underwent successful balloon
In patients with AS, an E/E′ ratio more or equal to 13 identified valvuloplasty. The X-ray before ABV shows cardiomegaly
the LV end-diastolic pressure greater than 15 mm Hg, with a and after ABV shows reduction in cardiomegaly (Figures 23E
sensitivity of 93 percent and a specificity of 88 percent. and F). The neonate was weaned off ventilator within 24 hours.
The ejection fraction (EF) improved from 35 to 55 percent. The
Infantile aortic stenosis17,64,65 surgical intervention, in absence of proper artificial valve, has
poor prospects of success. The extensive procedures like Ross
The adverse effects of small inflow, outflow, and/or cavity size operation provide alternative solutions. Left ventricular size
of the LV are cumulative. The accuracy of prediction of the and its maladaptive concentric hypertrophy remains the biggest
outcome based only on preoperative anatomy indicates that concern for outcome of any intervention done for restoration of
adequacy of valvotomy is not generally a limiting factor for biventricular morphology of the heart. Hence, with exceedingly
survival in this group of patients. It is possible to identify better results of Norwood and associated procedures, critical
486 subjects whose chance of survival is better after a Norwood analysis is desirable for selection of the procedure.
33
D e F
Figures 23A to F: A. Neonatal aortic stenosis. Transthoracic echocardiography (TTE) in apical four-chamber view shows dilated left ventricle
(LV) with concentric hypertrophy and changes in the papillary muscles; B. TTE in parasternal short-axis in 14 hrs old baby, shows pinpoint
aortic orifice (arrow); C and D. TTE (PSAX) shows increased valve area in same baby (post BAV); E. Pre-BAV X-ray chest in anteroposterior
view showing cardiomegaly; F. Post-BAV X-ray chest (same baby) showing improvement in cardiac size and improved PVH (pulmonary venous
hypertension), BAV = Balloon aortic valvuloplasty; PSAX = Parasternal short axis view.
There are several echocardiographic indicators to help 2. An indexed aortic root diameter of 3.5 cm/m2 or less
in diagnosis like the hypoplastic LV is usually globular and 3. An indexed mitral valve area of 4.75 cm2/m2 or less
does not extend to the cardiac apex. Additionally, LV inflow 4. An LV mass index of 35 g/m2 or less.
dimension (hinge point of posterior mitral leaflet to cardiac They selected 65 babies up to 33 days of age out of which
apex of less than 25 mm, mitral valve annulus diameter of 46 underwent valvuloplasty as a first procedure. Outcome
less than 9 mm, ventriculoaortic junction of less than 5 mm, all was predicted with 95 percent accuracy when they used the
measured from apical four chamber or long-axis view at end following equation:65
diastole will indicate hypoplastic LV. Left ventricular cross- Score = 14.0 (BSA) + 0.943 (AoR/m2) + 4.78 (LAR)
sectional area measured in the parasternal long-axis view that + 0.157(MVA/m2) – 12.03
included the mitral valve, AV and left ventricular apex at end A score less than – 0.35 is considered to be not compatible
diastole, of less than 2 cm2. with survival after two ventricle repair.
Rhodes et al analyzed the cases of critical AS applying one (BSA = Body surface area; AoR = aortic root dimencion
risk scoring system with good predictive value. in cm indexed to BSA; LAR = ratio of long axis of LV to
Risk scoring system for biventricular palliation or repair in long axis dimension of heart; MVA = mitral valve area [cm2]
critical AS: indexed to BSA).
For the four risk factors identified, the critical levels were: This scoring system has potential for errors and also pres-
1. A left ventricular long axis to heart long-axis ratio of 0.8 or ence of additional problems like MR may lead to fallacious
less calculation. 487
http://vip.persianss.ir
6 rheumatic heart disease and aortic stenosis22,23,66,67
table 5
Criteria of an abnormal exercise test in patients with
In developing countries rheumatic heart disease is not asymptomatic aortic stenosis
congenitAl VAlVAr lesions
uncommon. It is the most serious complication of rheumatic Symptoms during exercise: dyspnea, angina, syncope or
fever. Acute rheumatic fever follows 0.3 percent of cases near syncope
of group A beta-hemolytic streptococcal pharyngitis in • Fall in blood pressure or < 20 mm Hg rise in systolic blood
children. Rheumatic AV characterized by three leaflets, pressure during exercise
rolled up, thickened margins fusion of commissures between • < 80% of normal level of exercise tolerance
the aortic leaflets. AV is the second most favored site for • > 2 mm ST segment depression during exercise
(horizontal or downsloping, in comparison to baseline, not
rheumatic activity. It usually presents as combined lesions
attributable to other causes)
and rarely as an isolated involvement. Rarely, it manifests • Ventricular arrhythmias
as purely a stenotic or regurgitant lesion. The rheumatic AS
is a poor candidate for balloon valvuloplasty and also for
Ross operation. Chokalingam et al reported the prevalence of
table 6
isolated AV disease as 4.5 percent in patients below 18 years. Causes of aortic regurgitation
thickness. The chronic AR may occur due to variety of lesions. related normograms. They should be followed up serially. Any
However, AR is better tolerated in long term follow-up. undue dilatation or rapid increase in these parameters will
Clinically it presents with high systemic pulse pressure and very identify the patient at risk of development of aortic dissection
low diastolic blood pressure. Sometimes, diastolic pressures needing elective aortic root replacement procedure.45-48,50
can approximate to zero in chronic severe AR. It represents Beppu et al reviewed current concepts of anatomic
the inability of aortic root to maintain pressure in diastole due classification, pathophysiology, natural history, and clinical
to the incompetent AV which leads to increased LVEDP. The management of BAV disease with associated ascending aortic
significant AR is associated with central diastolic runoff of the aneurysms and suggested that optimal management of patients
blood into the LV cavity, which in turn may be reflected in the with BAV disease and associated ascending aortic aneurysms
classical physical findings (Tables 7 and 8). 17,18,22,23,41,59,60 often requires a thoughtful approach, careful assessment of
risk factors.43
aortic root dilatation
aortic regurgitation in aortic valve Prolapse in
Aortic root dilatation occurs in connective tissue disorders ventricular septal defect
such as Marfan syndrome, Ehlers-Danlos syndrome, Turner
syndrome and polyvalvular heart diseases. In connective In the presence of perimembranous or doubly committed
tissue disorders, aortic root dilatation is progressive. VSD, AV may prolapse progressively, prohibiting coaptation
Initially it involes sinus of Valsalva, ascending aorta, then of the cusps and leading to incremental AR.
dilatation progresses to involve aortic annulus leading to Saleeb et al reported that aortic cuspal prolapse and clinical
distortion of the AV and AR. While evaluating the patient AR are not uncommon in patients with subaortic VSDs. They
with connective tissue disorders such as Marfan syndrome, studied hundred patients, with a mean age at VSD diagnosis of
aortic root measurements should be taken at four levels: 0.1 +/– 0.5 years, with follow-up period of 7.1 +/– 10.1 years.
aortic annulus, sinus of Valsalva, STJ and ascending aorta Aortic cuspal prolapse developed in 14 patients (14%) at a
1 cm above the sinotubular junction and compared with age- mean age of 7.1 +/– 6 years (range 0.4–18.4). AR murmurs 489
http://vip.persianss.ir
6 table 8
Peripheral signs of aortic regurgitation
congenitAl VAlVAr lesions
were heard in 6 patients (6%) at a mean age of 5.1 +/– 3.1 Post-aortic valvuloplasty aortic regurgitation
years, all of whom had aortic cuspal prolapse and underwent Aortic regurgitation of varying degree is the usual finding
VSD closure and aortic valvuloplasty. Mori et al published after balloon aortic valvuloplasty and sometimes may
the data of 99 consecutive patients with supracristal VSD and lead to surgical intervention. Brown et al concluded in
found that the thirty patients (30%) had AV prolapse (VSD their retrospective study that although, transcatheter aortic
+ AoVP group), and 31 patients (31%) had AoVP with AR valvuloplasty is effective for relief of congenital AS, there are
(VSD + AoVP + AR group). In the VSD + AoVP group, AoVP steady long-term hazards for surgical AV reintervention and
was detected first by echocardiography at the age of 6.8 +/– replacement that are independent of factors like age of initial
4.2 years (mean +/– SD). In the VSD + AoVP + AR group, the intervention or severity of AS. They followed up 563 patients
interval from detection of AoVP to the appearance of AR was for a median follow-up period of 9.3 years. Survival free from
3.4 +/– 2.0 years.17,18,70,71 any aortic valve reintervention, was 89 ± 1% at 1 year, 72 ±
Why does prolapse occur in the adjoining VSD? The most 2% at 5 years, 54 ± 3% at 10 years, and 27 ± 3% at 20 years.
acceptable explanation is that this is the result of the interaction Freedom from AV replacement was 90 ± 2% at 5 years, 79
between the anatomical defects and hemodynamic factors like ± 3% at 10 years, and 53 ± 4% at 20 years.73 In multivariate
Venturi effect caused by a rapid blood flow through the VSD analyses, lower post-dilatation AS gradient and lower grade
in accordance to the Bernoulli’s theorem. With progress of of post-dilation AR were associated with longer freedom from
the disease, this syndrome is clinically subdivided into three AV replacement, but age, era, and pre-dilation AS severity
stages: were not.17,73
1. The prolapsing stage, which is characterized by the Venturi
effect Infective endocarditis and aortic regurgitation
2. The reversible AR stage, which has AR and the Venturi effect
3. The irreversible AR stage in which the corrosion of the AV Infective endocarditis can lead to acute or chronic AR,
is complete.72 depending upon the virulence of the bacteria. Aranki et al
Moreover, sometimes, the sinus of Valsalva may prolapse published a retrospective study of 2,000 patients of whom
without distorting the hinge point and and AV coaptation may 66 percent patients were those who underwent AV surgery
490 not be affected (Figures 24A and B). due to endocarditis of native valve.69 The operative mortality
33
for native valve IE was 7.4 percent.69 Endocarditis almost a mechanical adaptation to both pressure and volume overload.
eats away the valve in few of the cases. It may cause aortic In AR, compensatory hypertrophy decreases wall stress;
root abscess, embolization of vegetations and may leads to however ultimately hypertrophic changes are detrimental as
complications involving various organs. they induce contraction and relaxation abnormalities. These
abnormalities lead to progressive inadequacy of coronary
severIty oF regurgItatIon vascular supply. Studies have shown that with same mass/
volume ratio, chances of arrhythmias are more in patients with
With the use of two-dimensional echocardiography (left combined AR and AS than AS alone.17,23,41
ventricular dilatation, ventricular function), M-mode echo-
cardiography (ventricular dimensions), color flow mapping,
and pulsed Doppler interrogation, severity of regurgitation natural hIstory oF aortIc valve lesIons17,18,75-77
should be assessed (Figures 25A to D). Echocardiographic
criteria with the assessment of specific, supportive, and Progression of gradient across the aortic valve
quantitative parameters are given in Table 9. Table 10
describes the angiographic criteria for AR. Despite the lack of very long-term intervention-free data,
Calculation of effective regurgitant orifice (ERO) by natural history studies have provided important information.
proximal isovelocity surface area (PISA) method was Patients who present in infancy with AV stenosis generally
originally used for MR. Now it is a valid method for have more severe stenosis and higher mortality with or
regurgitatant AVs also. Though, the procedure is cumbersome without treatment. Twenty-five of the patients in the original
and needs more time than other methods. NHS-1 cohort were younger than 2-years-old; the 1-year
survival rate was 64 percent, and most had undergone surgical
ventricular dimensions and ventricular Function interventions. In contrast, the 25-year survival in-patients who
were 2 years of age or older at the time of original enrollment,
Left ventricular dimensions should be measured by traditional was 85 percent. An earlier study by Campbell, published in
M-mode done in parasternal long axis (PLAX) view. With 1968, found that the mean age of death in patients with AS was
significant AR, left ventricular end-diastolic dimension will be 35 years, with 40 percent mortality by age 30 and 60 percent
high because of the increased filling. Left ventricle end-systolic mortality by age. More than half of the patients who died had
dimension remains normal. Therefore, left ventricular fractional sudden unexpected death, whereas most of the remaining
shortening is increased. It shows capacity of LV to eject more deaths were due to progressive congestive heart failure. The
volume (normal stoke volume plus regurgitant volume). With notion that sudden death is extremely rare in the absence of
onset of LV failure, left ventricular end-systolic dimension starts preceeding symptoms has been challenged by several recent
increasing. Intervention should be done before left ventricular studies including NHS-2. About half of sudden death cases
end-systolic dimension reaches 55 mm (in adults). The LVH is from AS occurred during or immediately after exercise. 491
http://vip.persianss.ir
6
congenitAl VAlVAr lesions
A B
c D
Figures 25A to D: A. Echocardiographic image in parasternal long-axis view shows bicuspid aortic valve with severe aortic regurgitation;
B. Continuous wave (CW) Doppler cursor at abdominal aorta in chronic aortic regurgitation (AR) showing systolic forward (above the baseline)
flow and pan-diastolic flow reversal (below the base line) s/o severe AR; C. CW Doppler—mild AR; D. CW Doppler—severe AR. Image courtesy:
Dr Nagendra Chauhan
table 9
Grading of severity of aortic regurgitation
Although mild AS may remain stable for many years, bacterial endocarditis78,79
ultimate progression is the rule.9 It may be greater in children
than in adolescents and adults because of the inability of the Bacterial endocarditis risk has been reported to be as high as
valve orifice to increase in proportion to somatic growth. 1 percent per year, but is probably lower, based on the data
The outcome is highly correlated with the initial gradient, from NHS-2 where the incidence rate was 27.1 cases per
with those having higher gradients developing symptoms, 10,000 person years (0.27% per year). Although bacterial
dying, or having valve replacement sooner than those with endocarditis risk is present even in very mild aortic valve
lower gradients. In addition to the progression of AS, many stenosis, the incidence of endocarditis is higher in patients
patients may develop significant and progressive aortic valve with more severe stenosis. BAV endocarditis predominantly
regurgitation, particularly if they have had surgical valvotomy occurs in young adults and there is a strong male dominance
or percutaneous balloon valvuloplasty. (73–100%). Staphylococci and viridans streptococci have
accounted for nearly three-quarters of the cases, as in native
changes in aortic root17,18,75-77 valve endocarditis. Complications, especially heart failure and
valvular or myocardial abscesses are common. Most patients
Isolated BAV seems to have a relatively benign course in require surgery, often on an emergency basis. Recent surgical
childhood. However, compared with those with a normal series show that 25 to 54 percent of all infected AVs are bicuspid.
AV, those with BAV disease have a higher prevalence and
faster rate of ascending aortic dilatation which may culminate management oF aortIc valve dIsease
into dissection or rupture at a younger age. The fact that
pulmonary trunk shares this potential for abnormal dilatation,
medical management
suggests an embryological basis. The vascular smooth muscle
cells (VSMCs) that undergo apoptosis in the media of the In AS, medical management does not carry much role except
ascending aorta are of neural crest origin. There are 3 main for decongestive therapy in failing heart and supportive
histopathological features described in literature to define therapy like blood transfusion for very low hemoglobin or
the formerly called cystic medial necrosis: noninflammatory ventilation for very sick children. The neonates presenting
loss of VSMCs, fragmentation of elastic fibers, and increased early may get benefit from prostaglandin by keeping the PDA
basophilic ground substance within cell-depleted areas of the open (see chapter 5 on duct dependent circulation). With the
ascending aortic media. The pulmonary trunk demonstrates use of prostaglandin infusion, transport can be easy.
same histological feature in patients with BAV disease. The There is a definite role for medical management in
strong association between BAV and coarctation of aorta, both regurgitant lesions of the AV. Unless systolic function
with and without Turner syndrome, may indicate that BAV is abnormal, intervention is not recommended. Usually
disease involves the ascending aorta and aortic arch extending vasodilator therapy is most effective as it decreases the
to the ligamentum arteriosum, where most coarctations occur. afterload and improves the end systolic contraction indices
The convexity of the aorta is particularly affected by the and dimensions. Nowadays, ACE inhibitors are the drugs
medial degeneration, demonstrating less collagen, greater of choice. In presence of moderate severe LV dysfunction
elastic fragmentation, and fewer VSMCs. diuretic therapy is recommended.
493
http://vip.persianss.ir
6 Intervention in aortic stenosis78-87 D. In patients with left ventricular dysfunction normalization
of ventricular function following successful aortic valvotomy
Aortic Stenosis: Timing of Intervention82 may be associated with increase in gradients compared to
congenitAl VAlVAr lesions
c D
Figures 26A to D: A. Aortic root angiogram shows Prussian helmet appearance due to the doming of aortic valve (AV) with a negative shadow
caused by blood passing through a narrow orifice; B. BAV fluoroscopic image LAO 55° and cranial 15°: inset (picture) image of ascending
aortogram, showing partial opening of stenosed bicuspid AV (negative shadow) and main image is showing balloon valvoplasty in the same view;
arrow indicating waist of balloon; C. Pressure tracings on the monitor shows the left ventricular (LV) pressure (red) is 176 mm Hg and aortic
pressure (green) is 90 mm Hg, gradient is 86 mm Hg; D. The pressure tracings after successful balloon dilatation the LV pressure dropped to
150 and aortic pressure increased to 130 mm of Hg.The gradient reduced to 20 mm Hg
table 11
Differences in approach between aortic vs pulmonary balloon valvuloplasty based on references
B
A
c D
Figures 27A to D: Aortic valve repairtechniques.89-91 A. Leaflet suspension and subvalvular annuloplasty in aortic valve prolapse;
B. Restoring cup integrity; C. Leaflet extension using autologous pericardium; D. Triangular resection
associated with AR. They also defined the AV prolapse Type of Artificial Valves
echocardiographically.92 The artificial valve are designed to imitate the purpose of the
Normal AV cusp coaptation occurs approximately, at a native valves. There are two basic types of artificial heart
level, corresponding to the middle of the sinuses of Valsalva, valve:
i.e. halfway between the ventriculoaortic junction and STJ. Cusp 1. Mechanical valves
prolapse, therefore, is strictly defined as the motion of the cusp 2. Tissue valves.
free margin below this level. The AV prolapse may involve a
single cusp or all the three cusps. The prolapse of cusp can be Mechanical Valve
appreciated ‘relative’ to other cusps or “absolute’ in relation to
physiological coaptation level. Mechanical heart valves are more durable in comparison to
their bioprosthetic counterparts. Newer mechanical devices
aortic valve replacement 2,14,17,18,23,93-95 are bileaflet structure and the struts and occluders are made
out of either with pyrolytic carbon. Usually, the sewing
Aortic valve replacement is usually management of choice ring cuff is Teflon, polyester or dacron. Replacement with a
in absence of a successful repair technique. The mechanical mechanical prosthesis currently provides the most durable
valves have shown acceptable long-term results. Eventual result. Disadvantages associated with mechanical prosthesis
outcome of ballooning procedures or surgical repair is the are the constant need for anticoagulation and lack of growth
496 valvar replacement. potential. Evidently, these are the significant problems in small
children. These valves tend to produce noise. Postsurgical, 33
paravalvar leak and valve dysfunction may lead to re-
intervention (Figures 28A and B). The bacterial endocarditis
A B
497
Figures 28A and B: A. Transesophageal echocardiography (TEE) midesophageal short-axis view mechanical prosthetic valve in situ
in aortic position; B. 3D echocardiography, short-axis view showing paravalvar leak seen. Image courtesy: Nagendra Chauhan
http://vip.persianss.ir
6 many years. The patients with rheumatic aortic valve are not table 12
Various aortic valves for percutaneous implantation
good candidate for Ross procedure.95
congenitAl VAlVAr lesions
A B c D
498
Figures 30A to D: Transcutaneous aortic valve implantation (TAVI)
aortic stenosis in Fetus100-104 demanding. Fetal position and left ventricular size remain 33
the critical factors for technical success and good long-term
Aortic stenosis in fetus may eventually present as hypoplastic outcome of the procedure.102,103
http://vip.persianss.ir
6 reFerences 19. Davies MJ. Pathology of cardiac valve. London: Butterworth,
1980.
1. Smallhorn JF, Redington AN Anderson RH. Congenital
20. Bellhouse BJ, Talbot L. The fluid mechanism of Aortic valve J.
anomalies of the aortic valve and left ventricular outflow tract.
congenitAl VAlVAr lesions
http://vip.persianss.ir
6 75. Valdes-Cruz LM, Cayre RO. Miscellaneous anomalies of left
ventricular outflow tract. In: Valdes-Cruz LM, Cayre RO (Eds).
91. Pettersson GB, Ramankutty RM. Repair of bicuspid aortic
valve with severe regurgitation. MMCTS, 2010.
Echocardiographic diagnosis of congenital heart disease–An 92. Boodhwani M, Kerchove LD, Glineur, et al. Repair of Aortic
congenitAl VAlVAr lesions
embryologic and anatomic approach. Philadelphia New York valve prolapse, Multimedia manual of cardio-thoracic surgery
Lippincott-Raven publishers. 1999.pp.371-7. mmcts. 2008.003806 doi: 10.1510/mmcts.2008.2008.003806.
76. Mills P, Leech G, Davies M, et al. The natural history of a non- 93. Arnold R, Ley-Zaporozhan J, Ley S, et al. Outcome after
stenotic bicuspid aortic valve. Br Heart J. 1978;40:951-7. mechanical aortic valve replacement in children and young
77. Mahle WT, et al. Outcome of isolated bicuspid aortic valve in adults. Ann Thorac Surg. 2008;85:604-10.
childhood. J Pediatr. 2010;157:445. 94. Raja SG, Pozzi M. Growth of pulmonary autograft after ross
78. Yener N, Oktar GL, Erer D, et al. Review: Bicuspid aortic operation in pediatric patients. Asian Cardiovasc Thorac Ann.
valve, Ann Thorac Cardiovasc Surg. 2002;8:264-167. 2004;12:285-90.
79. McElhinney DB, Lock JE Keane JF, Moran AJ, Colan SD,Left 95. Raja SG, Atal manyuk I, Kostolny M, et al. In young patients
Heart Growth, Function, and Reintervention After Balloon with rheumatic aortic regurgitation compared to non-
Aortic Valvuloplasty for Neonatal Aortic Stenosis;Circulation. rheumatics is a Ross operation associated with increased
2005; 111: 451-458 incidence of autograft failure? Interact CardioVasc Thorac
80. Magee AG, Nykanen D, McCrindle BW, Wax D, Freedom RM, Surg. 2010;10:600-4.
Benson LN. Balloon dilation of severe aortic stenosis in the 96. Al-Lamee R, Godino C, Colombo A. Transcatheter aortic
neonate: comparison of anterograde and retrograde catheter valve implantation: current principles of patient and technique
approaches. J Am Coll Cardiol. 1997; 30: 1061–1066. selection and future perspective: Circulation Cardiovascular
81. Zeevi B, Keane JF, Castaneda AR, Perry SB, Lock JE. Neonatal interactions. 2011;4:387-95.
critical valvar aortic stenosis: a comparison of surgical and 97. Piper C, Kopfer C, Horstkotte D. Valve Disease Prosthetic
balloon dilation therapy. Circulation. 1989; 80: 831–839. valve endocarditis. Heart. 2001;85:590-3.
82. Consensus on Timing of Intervention for Common Congenital 98. Karchmer AW, Gibbons GW. Infections of prosthetic heart
Heart Diseases; working group on management of congenital valves and vascular grafts. In: Bisno AL, Waldvogel FA
heart diseases in India. Indian pediatrics: volume 45, february (Eds). Infections associated with indwelling medical devices.
17, 2008.p.121. Washington: ASM Press. 1994.pp.213-49.
83. Jindal RC, Saxena A, Juneja R, et al. Long-term results of 99. Baddour LM, Wilsom LM. Infection of prosthetic valve
balloon aortic valvulotomy for congenital aortic stenosis in and other cardiovascular devices: intravascular devices. In:
children and adolescents. J Heart Valve Dis. 2000;9:623-8. Mandell GL, Bennete JE, Dolin R, (Eds). Mandel Douglas,
84. Levine MJ, Berman AD, Safian RD, et al. Palliation of valvular and Bennette’s principle and practices of infectious diseases.
aortic stenosis by balloon valvuloplasty as preoperative 5th ed. Philadelphia, Pa: Elssevier: 1022-44.
preparation for noncardiac surgery. The American Journal of 100. McCaffrey FM, Sherman FS. Prenatal diagnosis of severe
Cardiology. 1988;62:1309-10. aortic stenosis. Pediatr Cardiol. 1997;18:276-81.
85. Thomson JD. Management of valvar aortic stenosis in children. 101. Maxwell D, Allan L, Tynan MJ. Balloon dilatation of aortic valve
Heart. 2004;90:5-6. in the fetus: a report of two cases: Br Hear J. 1991;65: 256-8.
86. Reich O, Marek J, Gilík J, et al. Long-term results of 102. McElhinney DB, Marshal AC, Wilkins-Haug LE, et al.
percutaneous balloon valvoplasty of congenital aortic stenosis: Predictors of technical success of postnatal biventricular repair
independent predictors of outcome. Heart. 2004;90:70-6. outcome after in utero aortic valvoplasty for aortic stenosis
87. Daehnert Rotzsch C, Wiener M et al. Rapid right ventricular with evolving hypoplastic left heart syndrome. Circulation.
pacing is an alternative to adenosine in catheter interventional 2009;120:1482-90.
procedures for congenital heart disease. Heart. 2004;90:1047-50. 103. Percutaneous fetal balloon valvuloplasty for aortic stenosis;
88. Ross J Jr. Afterload mismatch in aortic and mitral valve disease: NHS national institute of health and clinical excellence;
implications for surgical therapy J. Am Coll Cardiol. 1985;5:811. Issue date May 2006; http://www.nice.org.uk/nicemedia/
89. Carr JA, Savage EB. Aortic valve repair for aortic insufficiency live/11266/31597/31597.pdf.
in adults: a contemporary review and comparison with 104. Goldstein BH, Fifer CG, Armstrong AK, et al. Use of a Pressure
replacement techniques Eur J Cardiothorac Surg. 2004;25: Guidewire in Fetal Cardiac Intervention for Critical Aortic
6-15. Stenosis. Pediatrics. 2011;128:e716-9. Epub 2011 Aug 15.
90. Izumoto H, Kawazoe K, Oka T, et al. Leaflet Suspension 105. Apte SS, Paul A, Prakash S, Shum-Tim D. Current developments
and subvalvular annuloplasty in aortic valve prolapse Asian in the tissue engineering of autologous heart valves: moving
Cardiovasc Thorac Ann. 2009;17:278-81. towards clinical use.Future Cardiol. 2011;7:77-97.
502
Sec t i on
http://vip.persianss.ir
C hapter
Bentham J, Wilson N
http://vip.persianss.ir
7
Diseases of the aorta
a B
figures 1a and B: Echocardiographic assessment of the arch anatomy of a newborn infant in preparation for surgical repair. A. A 2.5 kg one-
day-old neonate who presented antenatally with ventricular and great artery disproportion. The left ventricle (arrow, LV) appears smaller than
the right and occasionally careful assessment of the LV, mitral valve, aortic valve and aortic arch dimensions are necessary to confirm suitability
for two ventricle repair. Although uncomplicated in this case, these decisions can be difficult; B. In the same infant as in (A) the ascending
and transverse arch appears adequately developed with coarctation clearly demonstrated distal to the left subclavian artery with a prominent
posterior shelf (arrow). There is still a large duct though this collection of findings should be sufficient for a surgical decision without need to
withhold PgE to allow ductal constriction to confirm arch obstruction. This infant underwent end-to-end anastomosis through lateral thoracotomy
on day three of life
figure 2: A neonate with coarctation and transverse and isthmus figure 3: A neonate with coarctation and isthmus arch hypoplasia.
arch hypoplasia. The aortic arch between the brachiocephalic artery Here, there is transverse arch hypoplasia at 3 mm in a 3.5 kg neonate
and left common carotid artery is hypoplastic. The arch after the (distance 2) with further tapering of the arch at the aortic isthmus to
left common carotid artery is also small. An extended end-to-end 2.4 mm (distance 4). As in Figure 2 an extended end-to-end
anastomosis was performed through a median sternotomy to achieve anastomosis was performed through a median sternotomy to achieve
a more satisfactory repair a more satisfactory repair
complex congenital heart disease, notably transposition of discrete coarctation through tubular hypoplasia to interruption
506 the great arteries, double outlet right ventricle, double inlet is open to debate. Recognizing such a spectrum of disease as
left ventricle, tricuspid atresia and hypoplastic left heart well as the typical patterns of associated anomalies where
syndrome. Whether there is a sequence of anomalies from coarctation of aorta is a frequent accompanying feature led
Rudolph to speculate that a reduction in the volume of blood instituted as part of resuscitation. Not infrequently inotropes 34
passing through the ascending aorta in fetal life is causative in are an important part of resuscitation in these circumstances
the development of coarctation.14 Although other etiological and occasionally emergency interventional or surgical relief
Increasingly, coarctation of aorta is diagnosed antenatally with older Child and Adult
suspicion raised by marked ventricular or great vessel dispro-
portion15 (Figures 1A and B). There is evidence for improved Older children and adults may present with systemic hyper-
outcome for these infants as prostaglandin E2 or E1 (PgE) can tension or a cardiac murmur. Less commonly they exhibit
be commenced in the hours following birth to maintain ductal complications of aortic obstruction including left ventricular
patency and systemic blood flow thus avoiding cardiovascular failure, infective endarteritis, intracranial hemorrhage, regur-
collapse.16 These infants do however, continue to present di- gitation of an associated bicuspid aortic valve, premature
agnostic difficulty postnatally as ductal patency is maintained coronary artery disease or aortic dissection or rupture.
such that aortic arch obstruction may not be immediately
evident on echocardiography. Often one can be confident to IMAgIng
proceed to treatment on the basis of echocardiographic morpho-
logical appearances of coarctation whilst if there is uncertainty Chest radiography
discontinuing PgE under close observation allowing ductal
constriction and aortic arch obstruction to develop before con- The asymptomatic older child may demonstrate a prominent
sidering treatment is prudent (Figures 1 to 3). aortic knuckle and rib notching. Rib notching is rare in early
Given the subtlety of the antenatal features of possible childhood and most likely seen beyond 10 years of age. Chest
coarctation postnatal presentation will remain frequent. Whe- radiography is neither diagnostic nor prognostic, but may
ther screening methods such as lower limb pulse oximetry contribute if there is complex disease.
prior to neonatal discharge will increase detection of this
lesion remains to be proven.16 Clinical suspicion should be echocardiography
raised by lower limb saturations less than 95 percent, an
upper-lower limb blood pressure difference of more than The characteristic features of coarctation of aorta on
20 mm Hg and weaker femoral pulses than the upper limb echocardiography is indentation of the posterior aorta by
pulses. When both upper and lower limb pulses are weak this a wedge or ‘shelf’ of tissue (Figures 1 to 3). This can on
may result in diagnostic confusion and may reflect reduced occasion be difficult to demonstrate in the presence of a large
cardiac output from many causes, most commonly an infant patent ductus in an infant maintained on a PgE infusion.
with pulmonary hypertension of the newborn, septicemia or Serial echocardiography may be required in this circumstance
left heart obstructive lesions (aortic stenosis and hypoplastic with PgE discontinued. The transverse and isthmus arch
left heart syndrome). An aberrant right subclavian artery dimensions can be clearly defined by suprasternal views
(ARSA) could theoretically fail to detect both a difference in with echocardiography. Doppler interrogation may not be
upper limb and lower limb blood pressure or pulse oximetry informative if ductal flow is large, but if the ductus is closed or
readings as the right subclavian artery may arise below the constricted classical features of acceleration with flow into and
site of coarctation. In practice, this is a rare association (less through diastole are easily demonstrated. Considerable clinical
than 3%). A bruit may be heard between the scapulae, but is judgement may be required in borderline cases particularly in
not typical of neonatal coarctation. the setting of complex hearts with multiple malformations.
Any neonate presenting with cardiovascular collapse should Aortic arch obstruction will most likely progress over time
undergo cardiac evaluation as part of a diagnostic workup and and the classical features of aortic arch obstruction are not
echocardiography forms the mainstay of diagnostic evaluation immediately apparent. Associated features need to be defined
of the aortic arch (Figures 4A to E). Such duct dependent by a full echocardiographic study as they will impact greatly
infants rarely present diagnostic difficulties and PgE can be on the management strategy (Figures 4 and 5).
507
http://vip.persianss.ir
7
Diseases of the aorta
a B C
D e
figures 4a to e: Associated findings in infants with coarctation can impact greatly on the treatment strategy adopted. A five-day-old infant who
presented collapsed and required resuscitation. A. M-mode study through the left ventricle. The left ventricle is dilated (left ventricle end diastolic
diameter 2.55 cm) and the cardiac function is impaired (fractional shortening 15%). (B1) There is persisting pulmonary artery hypertension
with severe elevation of pulmonary artery pressure (estimated at 64 mm Hg from TR jet velocity + RA pressure estimated from IVL diameter);
B. Mitral regurgitation is common in this scenario and interrogation for concomitant mitral valve anomalies is important; C. There is a large
ventricular septal defect (VSD, arrow) which extends from the inlet valves (arrow) to the outlet (D, arrow). There is a further apical VSD (red color
flow Doppler evident in (C) and a bicuspid aortic valve with dooming valve leaflets; E. With such a large VSD primary repair of coarctation and
VSD would involve increased risk of a long and difficult intensive care course. An end-to-end anastomosis and a pulmonary artery band was
performed after a period of stabilization on PgE. The VSD was subsequently closed at six months of age
Magnetic resonance Imaging aortic arch anatomy. Modern multislice scanners are able
to achieve sufficient resolution to be superior to MRI in
In the older child and adult, magnetic resonance imaging small infants and would be complimentary to detailed echo-
(MRI) is more informative than echocardiography and is the cardiography albeit at the expense of radiation exposure.
imaging modality of choice for planning intervention. MRI General anesthesia is rarely required.
is able to define accurately whether one or multiple sites of
obstruction exist, the proximity to the head and neck vessels Angiography
as well as the length of hypoplastic segments. MRI is also a
useful surveillance tool for complications following treatment With the advent of noninvasive imaging, angiography is
of coarctation and many units routinely perform MRI as part of generally not required as a diagnostic tool in the evaluation
transition from pediatric to adult practice particularly if there of native coarctation of aorta. Angiography is performed as
is a degree of systemic hypertension.19 Standard protocols part of interventional treatment of coarctation of aorta in the
have been extensively published. older child and adult but rarely in isolation. Occasionally,
diagnostic angiography is necessary to assess the adequacy
Computed tomography of repair and would form an important part of the interstage
assessment of aortic arch reconstructive surgery following the
508 Occasionally, computed tomography (CT) can be useful in Norwood procedure for example. The difficulty here however
infants where there is diagnostic uncertainty about complex is that, gradients obtained under general anesthesia bear little
indications for intervention in each case. Debate exists over 34
whether residual gradients and obstructions are acceptable in
the absence of systemic hypertension given the serious nature
Surgical treatments
The evolution of many surgical treatment strategies for
coarctation of aorta since the early 1940s highlights the fact
that each technique has its inherent advantages, disadvantages
and risk of long-term problems. Over the years, the primary
technique for most centers managing infant coarctation
remains end-to-end anastomosis having removed the segment
of obstructed aorta and all ductal tissue.23-26 From published
series no one technique is clearly superior as advocates of
alternative surgical strategies are able to achieve similar results.
figure 5: Associated findings in children with coarctation can There will be circumstances where options are limited and one
impact greatly on the treatment strategy adopted and careful for full
echocardiographic evaluation is essential. A two-year-old girl presents
technique is preferred in view of the arch anatomy even if
with a cardiac murmur to her local pediatrician. Coarctation of aorta associated with higher risk of complications. The capability to
and a volume loaded left heart was evident on echocardiography. offer more than one technique occasionally in the same patient
There was pulmonary hypertension and a large aortopulmonary will be an important prerequisite of success in managing the
window was found (arrow). Repair of aortic coarctation by end-to-end
anastomosis and repair of aortopulmonary window was performed with
diversity of aortic arch obstructions encountered.
resolution of pulmonary hypertension in the days following surgery.
The aortopulmonary window had been missed by an incomplete End-to-End Anastomosis Including Extended Repair
echocardiographic study at another institution
End-to-end anastomosis has become the procedure of choice
for many centers managing infant and neonatal coarc-
resemblance to gradients likely to be experienced by the tation.27,28 The mortality rate in uncomplicated patients is very
patient under stress. Consequently, an infusion of an inotrope low,23,29 but rises with more complex disease and associated
such as adrenaline may be required to reveal suspected residual lesions.29,30 Residual obstruction in up to 34 percent of patients
obstruction. In the setting of patients with univentricular is noted at early follow-up. Residual obstruction is strongly
circulation, such diagnostic studies may be important when associated with weight at the time of surgery.26,28-32,37 Whether
considering higher risk interventions once other therapeutic obstruction at follow-up can be defined as recoarctation
strategies have been exhausted. resulting from scar tissue formation or failure to adequately
treat the primary lesion is open to debate (Figures 6 to 9).
InDICAtIonS for treAtMent Managing tubular arch hypoplasia with an extended or end-to-
side repair may be preferable and highlights the importance of
In infants with hemodynamic compromise the indication careful pre-operative assessment.33
for treatment is unequivocal. In older patients a consistent
systolic blood pressure gradient between the arms and legs Subclavian Flap Repair
of more than 20 mm Hg may be considered as an indication
for treatment although this is not universally accepted.20,21 Concerns about inadequate relief of obstruction with subclavian
The gradient across the site of aortic obstruction will be flap repair and the long-term risk of aneurysm formation has
influenced by the degree of collateral vessel formation such rendered this technique less popular. Occasionally, subclavian
that gradient alone is not a good indication for treatment in flap repair may be combined with end-to-end anastomosis to
some patients. Systemic hypertension at rest or following more adequately treat long segment obstruction.33
provocation with exercise greater than the 97th percentile for
age along with evidence of important luminal stenosis would Interposition Grafts, Bypass Tube, Extra-anatomic
form indications for treatment in this group of patients.22 The Bypass Grafts
complexity of arch obstruction, the procedure related risk and
the likelihood of procedural success form important parts of In older patients and adults, there is significant concern about 509
the joint cardiac and surgical discussion as to the timing and the ability to sufficiently mobilize tissue in a timely fashion to
http://vip.persianss.ir
7
Diseases of the aorta
a B C
D e f
figures 6a to f: A two-year-old child who presented in the neonatal period with coarctation (A-C) and underwent end-to-end anastomosis has
significant tubular hypoplasia of the aortic arch after the left common carotid artery (D-E). The arch hypoplasia was evident following neonatal
surgery. In view of the infants age, angioplasty was performed with modest improvement in caliber of the arch (F1). A. There is a large duct with
bidirectional flow evident on the pulse wave Doppler (inset figure, predominantly right-to-left flow); B. There is a posterior shelf as substrate for
an evolving coarctation (arrow) and relative hypoplasia of the arch between the left common carotid artery (LCCA) and the left subclavian artery
(*); C. There is a bicuspid aortic valve; D. At two years of age a 3D MRI reconstruction demonstrates the hypoplastic arch segment proximal to
the site of repair; E. An arch angiogram through a 4 French pig-tail catheter confirms the MRI findings and angioplasty is performed; F. A small
aneurysm at the base of the left subclavian artery is evident. In view of this child’s age and aneurysm, the residual gradient was accepted with
a provisional plan for stent placement to the hypoplastic segment at greater than 25 kg
figure 8: Residual or recoarctation is not uncommon following surgery figure 9: Residual or recoarctation is not uncommon following surgery.
with the underlying arch anatomy being a critical factor in the likelihood This hypertensive teenager was initially palliated as a low-birth-weight
of recurrence. A three-month-old infant presents for follow-up following infant with a turn down procedure of the left subclavian artery. The
end-to-end anastomosis repair of neonatal coarctation. There is coarcted segment is still evident. An 18 mm surgical interposition graft
generalized hypoplasia of the aortic arch as well as the head and was placed across the coarctated segment and the left subclavian
neck vessels. No discrete obstruction is identified to guide therapeutic artery turn down left producing effectively a double aortic arch with a
intervention. The arch is augmented after the left subclavian artery satisfactory result
with a patch aortoplasty though the descending aorta is similarly small.
This infant most likely has a vasculopathy (no elastin mutation was
identified)
511
http://vip.persianss.ir
7
Diseases of the aorta
a B
C D
figures 10a to D: A 3 kg neonate presenting with coarctation of aorta (B) and a large apical muscular ventricular septal defect (A, VSD).
The aortic arch is repaired and a pulmonary artery band placed. The VSD closes spontaneously sufficiently that the pulmonary artery band
is removed in the catheter laboratory with an angioplasty technique at six months of age (C and C1). The aortic arch caliber is checked with
angiography (D). A. The large apical VSD is demonstrated (arrow); B. There is a posterior shelf evident after the left subclavian artery; C. In
preparation that the VSD may close spontaneously the surgeon has placed a clip to secure the pulmonary artery band that can be displaced
with an angioplasty balloon. The pulmonary artery band is demonstrated in this lateral angiogram. Angioplasty is then performed with a 12 mm
× 2 cm Tyshak II angioplasty balloon; D. An arch angiogram has been performed in lateral projection to confirm the integrity of the arch repair
may be more difficult to repair in a small heart whilst preserv- recent technological advance have become the preferred
ing satisfactory left ventricular function may be alternatively treatment option in older patients weighing more than 25 kg.
treated by placement of a pulmonary artery band with the in-
tention of further surgery at a later stage (Figures 10A to D). Balloon Angioplasty
a B
C D
figures 11a to D: Balloon angioplasty treatment of neonatal coarctation of aorta and childhood recoarctation of aorta. A. A 2.5 kg neonate
has been palliated with balloon angioplasty (B and B1, 8 mm × 3 cm Tyshak II balloon) of coarctation as a bridge to surgical repair following
further weight gain; C. Significant re-coarctation following end-to-end anastomosis in a two-year-old child has been managed with angioplasty;
D. There is improvement in the caliber of the obstructed segment but further procedures are likely to be required to allow for further growth later 513
in childhood (stent placement)
http://vip.persianss.ir
7 angioplasty.44 Furthermore, bare metal open cell designed The most frequent complication following interventional
stents potentially offer an effective solution for complex stent placement relates to vascular access with need for large
arch obstruction in adults and older children where balloon sheaths. This has undoubtedly improved with technological
Diseases of the aorta
angioplasty is often ineffective because of elastic recoil and advances allowing delivery of stents through smaller and
surgery may require extra-anatomic bypass grafts. There smaller sheaths as well as vascular closure techniques. Whether
remains concern, however that bare metal stents are still interventional treatments will become a panacea for managing
associated with aortic aneurysm formation with a long-term aortic arch obstruction from infancy to adult life remains to
risk of aortic rupture albeit less than the risk with balloon be realised, but the adaptability of these techniques to varying
angioplasty alone.45 Covered stents may thus be preferred situations makes aortic arch intervention an important part of
where possible (Figures 12 and 13).46-48 Covered stents a comprehensive cardiac program (Figures 13A to D).
are, however, relatively contraindicated if placed in such a
position as to occlude head and neck vessels. Head and neck PrognoSIS
vessels may be covered with a stent only after evaluation
of the circle of Willis and with the availability of vascular The natural history of coarctation of aorta is extremely poor.
surgical grafting. Complications relating to exclusion of the Campbell reported mortality in excess of 75 percent of patients
left subclavian artery, even in adults, are rare.49,50 by 46 years of age.62 In the largest follow-up series of 646
Placement of endovascular stents in infants and small patients who underwent treatment for simple coarctation of aorta
children (< 25 kg) remains a controversial therapy despite at the Mayo clinic between 1946 and 1981 the postoperative
improvements in methods of access, balloon and stent size 10-year survival rate was 91 percent, falling to 84 percent at 20
and the use of smaller and smaller sheaths.24,51 The fact that years and 72 percent at 30 years. Earlier age at operation was
children will by necessity, be committed to several future associated with improved survival.63 Causes of death included
cardiac catheter procedures because of need for stent re- premature coronary artery disease, left ventricular failure,
dilation causes concern for most; thus preferring surgical stroke, sudden cardiac death and ruptured aortic aneurysm.
alternatives, balloon angioplasty or stent therapy only as a Given such poor outcomes conservative management of
bridge to definitive surgery later in childhood52,53 or potentially important residual gradients is not an attractive option. However,
as a bridge to adult size stent placement.54 whether these risks may be reduced by adequately treating
Short-term published results for stent implantation to residual obstructions remains to be proven.64 Such a guarded
successfully manage native and recurrent coarctation in prognosis may in-part relate to a coexisting vasculopathy that
older children and adults suggest that stenting gives more poses a significantly increased risk of systemic hypertension
predictable and lasting results than balloon angioplasty. Death throughout a patient's life.65-67 Life-long follow-up, treatment
has been reported between 0 to 1.4 percent and neurological of systemic hypertension and intermittent surveillance imaging
damage between 0 to 3.7 percent.45-48,55-61 to detect occult obstruction and/or aneurysm are essential.
a B C
figures 12a to C: Interventional management of aortic coarctation in an eight-year-old child presenting with systemic hypertension. A. The 3-D
MRI reconstruction is helpful in planning the interventional procedure as there is a long segment coarctation. The appearances are similar to
those confirmed on angiography; B. and C. A covered Cheatham-platinum stent has been placed with immediate and complete resolution of arch
obstruction. No damage to the integrity of the aorta is evident, but periodic surveillance by MRI or CT imaging will be performed
514
34
C D
figures 13a to D: Ruptured aortic arch with emergent interventional treatment in a 16-year-old child presenting to the emergency department
with back pain and hemoptysis following subclavian flap repair of coarctation of aorta during infancy. A. A chest radiogram was performed which
demonstrates a large aneurysmal dilatation of the aorta that was confirmed with computed tomography (B., arrow); C. Covered stent placement
was performed in preference to emergency surgery as this was felt to be the safer option. Despite covering the aneurysmal segment with multiple
covered stents an endoleak is still visible (arrow); D. The following day a long vascular stent graft was used to exclude the endoleaks. LAO - left
anterior oblique view
http://vip.persianss.ir
7 5. Ferencz C, Rubin JD, McCarter RJ, et al. Congenital heart
disease: prevalence at livebirth. The Baltimore-Washington
23. Sakopoulos AG, Hahn TL, Turrentine M, et al. Recurrent aortic
coarctation: is surgical repair still the gold standard? J Thorac
Infant Study. Am J Epidemiol 1985;121:31-6. Cardiovasc Surg 1998;116:560-65.
Diseases of the aorta
6. Burn J, Brennan P, Little J, et al. Recurrence risks in offspring 24. Kothari SS, Juneja R, Saxena A, Reddy SC, Sharma S. Balloon
of adults with major heart defects: results from first cohort of dilatation of simple aortic coarctation in neonates and infants.
British collaborative study. Lancet 1998;351:311-16. Indian Heart J 1998;50:187-92.
7. Siggers DC, Polani PE. Congenital heart disease in male and 25. Ebeid MR, Prieto LR, Latson LA. Use of balloon-expandable
female subjects with somatic features of Turner’s syndrome and stents for coarctation of the aorta: initial results and intermediate-
normal sex chromosomes (Ullrich’s and related syndromes). term follow-up. J Am Coll Cardiol 1997;30:1847-852.
British heart journal 1972;34:41-6. 26. Tyagi S, Singh S, Mukhopadhyay S, et al. Self- and balloon-
8. Miettinen OS, Reiner ML, Nadas AS. Seasonal incidence of expandable stent implantation for severe native coarctation of
coarctation of the aorta. British heart journal 1970;32:103-07. aorta in adults. Am Heart J 2003;146:920-28.
9. Loffredo CA, Chokkalingam A, Sill AM, et al. Prevalence of 27. Barreiro CJ, Ellison TA, Williams JA, et al. Subclavian flap
congenital cardiovascular malformations among relatives of aortoplasty: still a safe, reproducible, and effective treatment
infants with hypoplastic left heart, coarctation of the aorta, for infant coarctation. Eur J Cardiothorac Surg 2007;31:649-
and d-transposition of the great arteries. American journal of 53.
medical genetics Part A 2004;124A:225-30. 28. Kaushal S, Backer CL, Patel JN, et al. Coarctation of the aorta:
10. Rose V, Gold RJ, Lindsay G, et al. A possible increase in the midterm outcomes of resection with extended end-to-end
incidence of congenital heart defects among the offspring of anastomosis. Ann Thorac Surg 2009;88:1932-938.
affected parents. Journal of the American College of Cardiology 29. Kobayashi M, Ando M, Wada N, et al. Outcomes following
1985;6:376-82. surgical repair of aortic arch obstructions with associated
11. Lewin MB, McBride KL, Pignatelli R, et al. Echocardiographic cardiac anomalies. Eur J Cardiothorac Surg 2009;35: 565-68.
evaluation of asymptomatic parental and sibling cardiovascular 30. Merrill WH, Hoff SJ, Stewart JR, et al. Operative risk factors
anomalies associated with congenital left ventricular outflow and durability of repair of coarctation of the aorta in the
tract lesions. Pediatrics 2004;114:691-96. neonate. Ann Thorac Surg 1994;58:399-402; discussion -3.
12. Gutgesell HP, Barton DM, Elgin KM. Coarctation of the aorta 31. Cobanoglu A, Thyagarajan GK, Dobbs JL. Surgery for
in the neonate: associated conditions, management, and early coarctation of the aorta in infants younger than 3 months:
outcome. Am J Cardiol 2001;88:457-59. end-to-end repair versus subclavian flap angioplasty: is either
13. Tani LY, Minich LL, Hawkins JA, et al. Spectrum and influence operation better? Eur J Cardiothorac Surg 1998;14:19-25;
of hypoplasia of the left heart in neonatal aortic coarctation. discussion-6.
Cardiol Young 2000;10:90-7. 32. Karamlou T, Bernasconi A, Jaeggi E, et al. Factors associated
14. Rudolph AM, Heymann MA, Spitznas U. Hemodynamic with arch reintervention and growth of the aortic arch after
considerations in the development of narrowing of the aorta. coarctation repair in neonates weighing less than 2.5 kg. J
The American journal of cardiology 1972;30:514-25. Thorac Cardiovasc Surg 2009;137:1163-167.
15. Franklin O, Burch M, Manning N, et al. Prenatal diagnosis 33. Thomson JD, Mulpur A, Guerrero R, et al. Outcome after
of coarctation of the aorta improves survival and reduces extended arch repair for aortic coarctation. Heart 2006;92:90-
morbidity. Heart 2002;87:67-9. 4.
16. de-Wahl Granelli A, Wennergren M, Sandberg K, et al. Impact 34. Botta L, Russo V, Oppido G, et al. Role of endovascular
of pulse oximetry screening on the detection of duct dependent repair in the management of late pseudo-aneurysms following
congenital heart disease: a Swedish prospective screening open surgery for aortic coarctation. Eur J Cardiothorac Surg
study in 39,821 newborns. BMJ 2009;338:a3037. 2009;36:670-74.
17. Lewis AB, Freed MD, Heymann MA, et al. Side effects of 35. Park Y, Lucas VW, Sklansky MS, et al. Balloon angioplasty
therapy with prostaglandin E1 in infants with critical congenital of native aortic coarctation in infants 3 months of age and
heart disease. Circulation 1981;64:893-98. younger. Am Heart J 1997;134:917-23.
18. Silove ED. Pharmacological manipulation of the ductus 36. Isner JM, Donaldson RF, Fulton D, et al. Cystic medial necrosis
arteriosus. Archives of disease in childhood 1986;61:827-29. in coarctation of the aorta: a potential factor contributing to
19. Puranik R, Tsang VT, Puranik S, et al. Late magnetic resonance adverse consequences observed after percutaneous balloon
surveillance of repaired coarctation of the aorta. European angioplasty of coarctation sites. Circulation 1987;75:689-95.
journal of cardio-thoracic surgery: official journal of the 37. Fletcher SE, Nihill MR, Grifka RG, et al. Balloon angioplasty
European Association for Cardio-thoracic Surgery 2009;36: of native coarctation of the aorta: midterm follow-up and
91-5; discussion 5. prognostic factors. Journal of the American College of
20. Beekman RH, Rocchini AP, Dick M 2nd, et al. Percutaneous Cardiology 1995;25:730-34.
balloon angioplasty for native coarctation of the aorta. Journal 38. Redington AN, Booth P, Shore DF, et al. Primary balloon
of the American College of Cardiology 1987;10:1078-084. dilatation of coarctation of the aorta in neonates. British heart
21. Mendelsohn AM, Lloyd TR, Crowley DC, et al. Late follow- journal 1990;64:277-81.
up of balloon angioplasty in children with a native coarctation 39. Lock JE, Bass JL, Amplatz K, et al. Balloon dilation angioplasty
of the aorta. The American journal of cardiology 1994;74:696- of aortic coarctations in infants and children. Circulation
700. 1983;68:109-16.
22. Rao PS, Solymar L. Transductal balloon angioplasty for 40. Al-Ata J, Arfi AM, Hussain A, et al. Stent angioplasty: an
516
coarctation of the aorta in the neonate: preliminary observations. effective alternative in selected infants with critical native
American heart journal 1988;116:1558-562. aortic coarctation. Pediatric cardiology 2007;28:183-92.
41. Holzer CE, Jr. Gunshot wounds involving the abdominal aorta;
a report of two cases. Surgery 1948;23:645-52.
obstruction. Catheterization and cardiovascular interventions:
official journal of the Society for Cardiac Angiography and
34
42. Shaddy RE, Boucek MM, Sturtevant JE, et al. Comparison of Interventions 2010;76:852-59.
517
http://vip.persianss.ir
C hapter
Classification
The classification of IAA by Celoria-Patton is based on the
site of the interruption (Figure 1).7
Type A: Distal to the left subclavian artery (1/3 of cases).
Type B: Distal to the left common carotid artery, between the
left subclavian artery and the left common carotid
artery (most common in nearly 2/3 of cases).
Type C: Proximal to the left common carotid artery, between
left common carotid artery and braciocephalic
(innominate) artery (least common in around 1%
of cases).
Each type is divided into three further subtypes:24
a. Subtype 1: Normal subclavian artery
b. Subtype 2: Aberrant subclavian artery
Figure 2: Autopsy specimen of aortic arch Interruption: The arch is
c. Subtype 3: Isolated subclavian artery that arises from the connected to the descending thoracic aorta (DTA) by a slender cord
ductus arteriosus. of tissue (arrow) in interrupted segment—Type A. The ductus (D)
These three types of IAA are distinct anatomical entities. continues as DTA. AA = Ascending aorta; LAA = Left atrial appendage;
Shone’s complex having multiple obstructive lesions of the LCCA = Left common carotid artery; LSA = Left subclavian artery; PT
left side of heart is implicated with this anomaly. = Pulmonary trunk; RBCA = Right brachiocephalic artery; RV = Right 519
ventricle. Image courtesy: Dr Pradeep Vaideeswar
http://vip.persianss.ir
7 intracardiac communications. The differential cyanosis may
or may not be clinically appreciated.27
The patients with TGA and IAA type B exhibit a distinct
Diseases of the Aorta
Clinical Presentation
the insertion of the ductus arteriosus has a lumen and appears
to continue as the DTA (Figure 3). The right ventricle is The clinical presentation of IAA is similar to that in patients
hypertrophied and somewhat dilated. The parietal band of the with COA and they are usually clinically stable as long as the
crista supraventricularis is often absent. The aortic valve is PDA remains open. These neonates present on the first day
bicuspid in nearly half of the autopsied specimens.25 Other of life and become desperately ill whether they have other
multiple cardiac anomalies are usually present. major cardiac defects or not. They are in cardiogenic shock,
tachypneic, with increased work of breathing and may appear
Pathophysiology terminally ill with multiorgan dysfunction. The neonates with
PDA may survive longer than a few weeks. They may or may
The IAA is a duct-dependent anomaly. The PDA is necessary not be cyanotic, as this is dependent on the associated cardiac
for the adequate blood supply to the descending aorta. The defects.14
neonate appears ill in the first few days of life and develops
cardiogenic shock, metabolic acidosis and multiorgan Pulse
dysfunction as the spontaneous closure of the PDA occurs.
The neonates with COA present with congestive heart failure Proper examination of the peripheral pulses gives a definite
in the 2nd week of life, probably due to the presence of some clue to the diagnosis of IAA. However, the accurate
antegrade flow through the obstructed isthmus. In the setting examination of all the pulses in a very sick neonate is often
of an intact atrial and ventricular septum, the lower half of the difficult. All the pulses are well felt if the ductus is patent.
body will be supplied by the PDA with desaturated blood and If lower limb pulses are feeble with a radio femoral delay, it
differential cyanosis will be present.26 indicates the ductus is closed and patient has collaterals. If the
The pathophysiology of IAA with VSD and/or atrial septal upper limb pulses are weak then severe LVOTO, ventricular
defect (ASD) is different. A left-to-right shunt across ASD or dysfunction and/or severe aortic stenosis must be suspected.28
VSD level is present and the blood that is ejected from the If the left brachial pulse is diminished or absent, it indicates
right ventricle and shunted through the PDA to the descending that the left subclavian artery is arising from the descending
520 aorta is less desaturated than the blood in patients without aorta distal to the interruption. The weak right brachial pulses
may be present in patients with an aberrant right subclavian Aortic knob is absent. Depending on the site of interruption, 35
artery arising below the interruption. If carotid pulses are either unilateral or bilateral rib notching may be seen in
well felt, but both upper (brachial) and lower limb (femoral) older patients. Origin of one subclavian artery distal to the
A B
Figures 4A and B: A. Transthoracic echocardiography (TEE) in suprasternal view illustrates the interruption of aorta (IAA); B. TTE in high ductal
view illustrates the patent ductus arteriosus (PDA) continuing as the descending aorta (DAO). AAO = Ascending aorta; MPA = Main pulmonary 521
artery.
http://vip.persianss.ir
7
Diseases of the Aorta
A B C
Figures 5A to C: Computed Tomography 3D images of interruption of aortic arch (IAA) type B. A. Anteroposterior view showing ascending aorta
(AAO) giving origin to innominate trunk (INN T) and left common carotid (LCCA) arteries with nonvisualization of aortic arch. Markedly dilated
main pulmonary artery (MPA) is seen; B. Direct left lateral view showing dilated MPA with patent ductus arteriosus (PDA) which continues as
descending thoracic aorta (DAO) with nonvisualization of the aortic arch. Note left subclavian artery (LSA) is seen arising from upper part of
DAO; C. Right posterior oblique view showing clearly visualized IAA distal to LCCA (type B) with ductus continuation of DAO. LA = Left atrium;
LPA = Left pulmonary artery; RPA = Right pulmonary artery; RV = Right ventricle. Image courtesy: Dr Hala ElMarsafawy
PGE1 and simultaneously the shock, hypoxia, hypercarbia tissue is removed and the left common carotid artery can
and acidosis should be treated. The goal of therapy is to also be turned down after division. The distal left common
maintain optimal descending aorta perfusion with right-to-left carotid artery is anastomosed to the right carotid artery.
shunting across the PDA. This can be monitored by physical Associated defects should be addressed. Care should be
examination (peripheral pulses, perfusion and urine output). taken to use irradiated blood in patients with associated
A preductal saturation above 90 percent and a postductal DiGeorge syndrome. Patients with an associate single
saturation of approximately 70 percent signifies good gas ventricle physiology will require arch reconstruction and a
exchange and appropriate distribution of the cardiac output.28 pulmonary artery band to limit pulmonary blood flow, to
Once the neonate has been stabilized, surgical correction allow the patient to go through a staged Fontan pathway.
should be contemplated as soon as possible. Type A interruption can be treated like a coarctation and
after mobilization, anastomosis can be done after excising
Surgery the ductal tissue. A reverse left subclavian flap can be used to
reconstitute the arch (Figure 6).
The surgery for interrupted aortic arch depends on the type of
defect and the associated defects. The current preference is an
one-stage approach through the median sternotomy, though
a type A defect can be treated via lateral thoracotomy as an
exaggerated coarctation.
Correction via median sternotomy has been classically
done using profound hypothermia and circulatory
arrest. The advent of better aortic cannulae, innominate
artery perfusion and low flow cerebral perfusion with
deep hypothermia and with moderate hypothermia with
innominate artery perfusion can be done. Perfusion of the
lower body can be done via a second arterial cannula placed
through the pulmonary artery via the ductus arteriosus
with snaring of the ductus during cardiopulmonary bypass.
Adequate mobilization of the cerebral vessels and aorta is
needed to create a tension less repair. The aortic cannula is
passed through the innominate artery and selective cerebral
perfusion is instituted at the target temperature after snaring
Figure 6: Interruption (Type A) repaired with a subclavian artery turn
the cerebral vessels. The ductus is divided and all ductal down and augmentation with a Gore-Tex patch via a left thoracotomy
522
Prognosis Congenital Heart Disease, 6th edition. Philadelphia. Saunders, 35
The IAA is invariably a fatal illness, with death occurring an imprint of Elsevier Inc. 2012. pp. 101-128.
within days of birth. If the condition is left untreated, 90 4. Collins-Nakai RL, Dick M, Parisi-Buckley L, et al. Interrupted
http://vip.persianss.ir
7 23. Yang DH, Goo HW, Seo DM, et al. Multislice CT angiography
of interrupted aortic arch. Pediatr Radiol. 2008;38:89-100.
27. Muñoz R, Tsifansky M, Morell VO. Interrupted Aortic Arch.
In: Muñoz R, Morell VO, Cruz EM, VetterlyVO (Eds). Critical
24. Goo HW, Park IS, Ko JK, et al. CT of congenital heart Care of the Children with Heart Disease. Springer-Verlag
Diseases of the Aorta
disease: normal anatomy and typical pathologic conditions. London Limited; 2010. pp. 267-72.
Radiographics. 2003;23:S147-65. 28. McCrindle BW, Tchervenkov CI, Konstantinov IE, et al.
25. Arey JC. Cardiovascular Pathology. Philadelphia: WB Risk factors associated with mortality and interventions
Saunders 1981. in 472 neonates with interrupted aortic arch: a Congenital
26. Matsui H, Adachi I, Uemura H, et al. Anatomy of coarcta- Heart Surgeons Society study. J Thorac Cardiovasc Surg.
tion, hypoplastic and interrupted aortic arch: relevance to 2005;129:343-50.
interventional/surgical treatment. Expert Rev Cardiovasc Ther. 29. Pongiglione G. Aortic arch interruption. Orphanet Encyclope-
2007;5:871-80. dia. Februrary 2004.
524
c hapter
Maitri Chaudhuri
Embryology
normal development
The formation of vascular rings is best understood from the
hypothetical model of double aortic arch as proposed by the
eminent cardiac pathologist Dr Jesse E Edwards in 1948.4 In
this model, the ascending and descending aorta are connected Figure 1: This schematic diagram shows the hypothetical model for
by symmetrical arches on each side, thus forming a complete double aortic arch as proposed by Jesse Edwards. LAA = Left aortic
vascular ring around trachea and esophagus. Each arch gives arch; LCCA = Left common carotid artery; LPA = Left pulmonary
artery; LSA = Left subclavian artery; PT = Pulmonary trunk; RAA =
origin to ipsilateral common carotid and subclavian arteries.
Right aortic arch; RCCA = Right common carotid artery; RPA = Right
Also on each side, corresponding ductus arteriosus is located pulmonary artery; RSA = Right subclavian artery. Courtesy: Reprinted
connecting the ipsilateral pulmonary artery and subclavian with permission from reference 1
http://vip.persianss.ir
7 Abnormal development
By following this model, the abnormalities can be either
Diseases oF the aorta
IndIVIduAl AnomAlIEs
Embryology
Double aortic arch is the tightest and most common vascular
anomaly.5 Embryologically, both the arches of the hypothetical
double arch model persist on two sides of the trachea, without
regression of any segment.
Morphology
Here the ascending aorta arises normally, but as it leaves the
pericardium, it bifurcates into left and right arches, on either
Figure 2B: This schematic diagram illustrates that in continuation of
Figure 2A, the disappearance of right aortic arch distal to the origin of side of trachea and then they join posteriorly to form the
the right subclavian artery (RSA), along with right sided ductus. LAA descending aorta. The left arch passes anteriorly and to the left
= Left aortic arch; LCCA = Left common carotid artery; LPA = Left of trachea and is joined by left ductus, where it becomes the
pulmonary artery; LSA = Left subclavian artery; PT = Pulmonary trunk;
descending aorta. The right arch passes to the right and then
RAA = Right aortic arch; RBA = Right brachiocephalic artery; RCCA =
Right common carotid artery; RPA = Right pulmonary artery. Courtesy: posterior to esophagus to join the left sided descending aorta,
Reprinted with permission from reference 1 thereby completing the vascular ring6 (Figures 3A and B).
526
are equal (balanced) and in remaining 25 percent, the left arch 36
is dominant (left dominant). The apex of the larger arch is
located at a higher level. In the usual right dominant arch, the
http://vip.persianss.ir
7
Diseases oF the aorta
Figure 4B: In majority of cases, the left sided ductus persists and the Figure 4D: This computed tomography (CT) angiogram depicts a right
left aortic arch regresses distal to the origins of left subclavian artery aortic arch with mirror image branching pattern in a 20-year-old lady
(LSA) and the left ductus, along with the right sided arterial ductus. After with tetralogy of Fallot with aortopulmonary collaterals from left internal
birth, the left sided ductus connects the base of left brachiocephalic mammary artery. LCA = Left carotid artery; LIA = Left innominate
or subclavian artery to the left pulmonary artery. Persistence of right artery; LSA = Left subclavian artery; MAPCA = Major aortopulmonary
sided arterial ductus is uncommon. LBA = Left brachiocephalic artery; collaterals; RCA = Right carotid artery; RSA = Right subclavian artery;
LCCA = Left common carotid artery; LPA = Left pulmonary artery; PT Courtesy: Reprinted with permission from Dr Aysel Turkvatan, Ihtisas
= Pulmonary trunk; RAA = Right aortic arch; RCCA = Right common Hospital, Turkey, Korean J Radiol. 2009;10:176-84
carotid artery; RPA = Right pulmonary artery; RSA = Right subclavian
artery; Courtesy: Reprinted with permission from reference 1
Figure 5c: Computed tomography (CT) angiogram showing right aortic arch with aberrant left subclavian artery (ALSA) in a 45-year-old
asymptomatic woman with anterior and posterior volume rendering images. LCA = Left carotid artery; RAA = Right aortic arch; RCA = Right
carotid artery; RSA = Right subclavian artery; RAA = Right aortic arch, arrows showing Kommerell diverticulum. Courtesy: Reprinted with
permission from Dr Aysel Turkvatan, Ihtisas Hospital, Turkey, Korean J Radiol. 2009;10:176-84
529
http://vip.persianss.ir
7
Diseases oF the aorta
a B
Figures 6a and B: These schematic diagrams show the mode of formation of the right aortic arch (RAA) with aberrant left subclavian artery
(LSA) and right sided arterial ductus, the pattern following the same format as for Figures 5A and B. In the fetal and postnatal circulations,
this arrangement produces a vascular sling on the right side of the trachea and esophagus. This is a rare combination. LAA = Left aortic arch;
LCCA = Left common carotid artery; LPA = Left pulmonary artery; PT = Pulmonary trunk; RCCA = Right common carotid artery; RPA = Right
pulmonary artery; RSA = Right subclavian artery. Courtesy: Reprinted with permission from reference 1
Right Aortic Arch with Aberrant Left Subclavian Artery with between origins of RCCA and RSA and disappearance of right
Persistent Right Ductus ductus (Figures 7A and B). The ARSA remains attached to the
distal part of right aortic arch. The ARSA and the remnant of
Right aortic arch with aberrant left subclavian artery with right aortic arch take a retroesophageal course. Previously this
persistent right ductus is a rare anomaly embryologically anomaly was called ‘arteria lusoria’. Usually the left ductus
explained by abnormal regression of left arch segment persists in this case and therefore an incomplete vascular ring
between LSA and LCCA and disappearance of left ductus and arises.
persistence of right ductus (Figures 6A and B).
This produces an incomplete encirclement or vascular Morphology
sling around right side of trachea and esophagus.
The right subclavian artery originates as the last vessel of
Right Aortic Arch with Aberrant Origin of Left Brachio- the aortic arch, from the junction of the aortic arch with the
cephalic Artery descending aorta. If the right ductus persists and the left one
disappears, then a complete vascular ring will be produced. The
This is rare and arises from abnormal regression of left arch ARSA courses behind the esophagus in 80 percent of cases,
segment proximal to LCCA with persistent left ductus. Again between esophagus and trachea in 15 percent, and anterior
this produces a complete vascular ring. to trachea in remaining 5 percent (Figure 7C). The aberrant
subclavian artery is usually an isolated malformation, although
left Aortic Arch with Aberrant right subclavian Artery it is associated with cardiac malformations in 12 percent of
with Persistent left ductus cases. The most frequent associated anomalies are TOF, aortic
coarctation, and interruption of the aortic arch.12
Left aortic arch with aberrant right subclavian artery with
persistent left ductus (PLD) is the most common anomaly of circumflex Aortic Arch
the aortic arch; however, it is usually asymptomatic.
Circumflex aortic arch is a rare anomaly, where the aortic arch
Embryology and the proximal part of descending aorta are on contralateral
sides of the spine. Here, the aortic arch makes an additional
530 Aberrant right subclavian artery (ARSA) with PLD occurs arch posterior to trachea and esophagus to reach the descending
when the embryological right arch has an abnormal regression aorta13 (Figures 8A and B).
36
Figures 7a and B: These schematic diagrams show the morphogenesis and postnatal structure of left aortic arch with aberrant origin of right
subclavian artery and left sided arterial ductus. In the hypothetical model, the red bars indicate the segments that regress. In the postnatal
circulation, a vascular sling is formed on the left side of trachea and esophagus. LCCA = Left common carotid artery; LPA = Left pulmonary
artery; LSA = Left subclavian artery; PT = Pulmonary trunk; RAA = Right aortic arch; RCCA = Right common carotid artery; RPA = Right
pulmonary artery; Courtesy: Reprinted with permission from reference 1
Figure 7c: Computed tomography (CT) angiogram showing left aortic arch with aberrant right subclavian artery in a 66-year-old lady with
dysphagia. 3D reconstruction show ARSA with diventiculum of Kommerell at its origin (white arrows). ARSA = Aberrant right subclavian artery;
LAA = Left aortic arch; LCA = Left carotid artery; LSA = Left subclavian artery; RCA = Right carotid artery. Courtesy: Reprinted with permission
from Dr Aysel Turkvatan, Ihtisas Hospital, Turkey, Korean J Radiol. 2009;10:176-84
This occurs more commonly with a right sided aortic arch. cervical Arch
The pattern of branching is as follows: 1st branch—LCCA,
2nd and 3rd branches—RCCA and RSA respectively and the The arch is called cervical when its apex reaches into the neck
terminal branch is the LSA arising at the point of transition above the clavicles. This produces a pulsatile swelling in the
of the retroesophageal arch to the left sided descending aorta. neck. This can be associated with a retroesophageal arch or even 531
Hypoplasia of the retroesophageal segment of the arch is double aortic arch. This produces overcrowding of structures
common. within the narrow neck and causes respiratory compression.14
http://vip.persianss.ir
7 In patients with coexisting cardiac diseases, RAA with mirror
image branching is the most common lesion. This is almost
always associated with congenital cardiac anomalies. 1/4th
Diseases oF the aorta
Symptoms
Symptoms depend on tightness of the ring and associated
tracheobronchomalacia. Respiratory symptoms manifest in
early infancy and esophageal symptoms develop later. The
earliest presentation is seen with children with double aortic
arch.
A. Manifestations due to upper airway, i.e. tracheobronchial
compression:
• Inspiratory stridor characteristically worsened by
inspiration, exertion or crying and its severity fluctuates
with change in position. Stridor is accentuated in supine
than lateral position. Some infants prefer opisthotonic
posture to relieve tracheal compression.
• Expiratory wheezing and tachypnea.
Figure 8B: This 3D reconstructed computed tomography (CT) • Hoarse cry.
angiogram shows a circumflex aortic arch. AAo = Ascending aorta;
DAo = Descending aorta; * = Retroesophageal circumflex arch • Persistent barking cough—‘seal bark’ cough17
• Apnea especially in children with brachiocephalic artery
compression and in those with complete tracheal rings.
B. Manifestations due to esophageal obstruction:
clInIcAl PrEsEntAtIon oF VAsculAr rIngs • Dysphagia usually to solids. This may be caused by
aneurysmal dilatation of diverticulum of Kommerell or
Epidemiology elongation of aorta.
• Frequent aspiration pneumonitis
Vascular rings of aortic origin represent 1 to 3 percent of • ‘Dysphagia lusoria’—difficulty in swallowing due to trick
all congenital heart diseases, although exact incidence may of nature. In 1761, David Bayford performed autopsy on
be underestimated.15 ARSA is the most common anomaly a 63-year-old woman with lifelong swallowing problems
532 (0.5% of autopsy series). The incidence is especially high and noted an ARSA coursing posterior to esophagus and
(38%) among Trisomy 21 children with heart disease. thereby indenting it. He opined that this abnormal course
of the artery caused deglutition problems and coined the dIAgnostIc WorKuP 36
term ‘dysphagia lusoria’.
The ARSA is usually asymptomatic and occurs in 1 in chest X-ray
barium Esophagogram
Although the use of barium esophagogram has been almost
abandoned in modern medicine, Baker and Berdon et al
had proposed a very efficient diagnostic algorithm based on
its findings (Box 1).20 The anterioposterior, right anterior
Figure 9a: This schematic diagram shows the mechanism of oblique, left anterior oblique views are fundamental (Figures
dysphagia lusoria, where an aberrant right subclavian artery courses 11A to C).
posterior to esophagus and compresses it. LCCA = Left common
carotid artery; LSA = Left subclavian artery; RASA = Right aberrant
subclavian artery; RCCA = Right common carotid artery.
Figure 9B: This computed tomography (CT) angiogram shows left aortic arch with aberrant right subclavian artery from posterior view. It
is not a true ring. If the base of right subclavian artery gets dilated, then it causes compression to esophagus and is called arteria lusoria.
Courtesy: Reprinted from Siegel MJ, Smithius R. Vascular anomalies of aorta, pulmonary and systemic vessels, Radiology assistant, /www. 533
radiologyassistant.nl/en/
http://vip.persianss.ir
7
Diseases oF the aorta
a B c
Figures 10a to c: A. This chest X-ray in frontal view shows a right sided aortic arch with arrow depicting the right arch. The tracheal air column
is displaced to the left by right arch. RAA = Right aortic arch, T = Trachea; B. This chest X-ray shows two paratracheal soft tissue densities (*) on
both sides of trachea in a patient with double aortic arch; C. This chest X-ray in lateral view shows anterior bowing of trachea. When the aortic
arch is right sided and an aberrant left subclavian artery arises from diverticulum of Kommerell (arrows), the diverticulum pushes forwards the
trachea
a B c
Figures 11a to c: A. Barium esophagogram in bilateral oblique view showing extrinsic impression (arrow) on posterior esophageal wall;
B. Barium esophagogram in lateral view showing bilateral posterior indentation (arrow) of the upper esophagus in a child with double aortic arch.
Arrow shows location of anomaly. Courtesy: Reprinted from Berrocal T, et al. Radiographics 1999;19:855-72); C. This barium esophagogram
shows the anterior compression of esophagus and arrow shows the location of anomalous left pulmonary artery coursing between the trachea
and esophagus. Courtesy: Reprinted from reference 20
http://vip.persianss.ir
7
Diseases oF the aorta
a B c
D e
Figures 12a to e: A. Echocardiogram in suprasternal short axis view showing a left sided aortic arch with 1st arch vessel, i.e. brachiocephalic
artery (BCA) coursing towards the right and dividing into right subclavian and right common carotid arteries. B. Echocardiogram in suprasternal
short axis view showing a right sided aortic arch with 1st arch vessel, i.e. BCA coursing towards the left and dividing into left subclavian and
left common carotid arteries. C. This echocardiogram in suprasternal short axis view shows the double aortic arches on corresponding sides
of trachea. arrow shows the position of trachea; D. This subcostal echocardiographic view shows a double aortic arch with ascending aorta
bifurcating into right and left aortic arches after it becomes extrapericardial. E. This echocardiogram in suprasternal view shows left aortic arch
with aberrant right subclavian artery. The picture on left side shows a suprasternal short axis view where the 1st branch does not bifurcate but
instead continues upwards, forwards and right wards, characteristic of right common carotid artery. The picture on right side shows that on
inferior angulation of the transducer, the aberrant right subclavian artery arises from the distal portion of descending aorta on the left side of the
midline. Ao = Aorta; AAo = Ascending aorta; LAA = Left aortic arch; LCCA = Left common carotid artery; LSA = Left subclavian artery; RAA =
Right aortic arch; RCCA = Right common carotid artery; RSA = Right subclavian artery.
a B
Figures 13a and B: A. Transthoracic echocardiogram in modified suprasternal view shows ascending aorta (AAO) bifurcating into right aortic
arch (RAA) and left aortic arch (LAA); B. Left ventricular (LV) angiogram in frontal view illustrates double aortic arch with PDA forming the
vascular ring. C.Volume rendered computed tomography angiogram of double aortic arch in a one and half year old child, illustrates bigger right
aortic arch (RAA) giving rise to right subclavian artery (RSA) and right common carotid artery (RCCA) and relatively smaller left aortic arch (LAA)
giving rise to left subclavian artery (LSA) and left common carotid artery (LCCA). AO = Aorta; DAO = Descending aorta; PA = Pulmonary artery.
Image courtesy: Dr. IB Vijayalakshmi
536
Box 3: Surgical Procedures in Vascular Rings28 pulmonary artery (MPA), arises extrapericardially from the 36
posterior aspect of right pulmonary artery (RPA) and then
Double aortic arch Division of the smaller of the two
takes a hairpin bend towards the left lung in the space between
http://vip.persianss.ir
7 diagnostic Workup
Chest X-ray
Diseases oF the aorta
Barium Esophagogram
The anomalous LPA is seen as a rounded density between
air-filled distal trachea and barium-filled esophagus in lateral
view with anterior indentation of esophagus.35
Figure 14: This schematic diagram shows the classical pulmonary Echocardiogram36,37
arterial (PA) sling where the left pulmonary artery arises from the right
pulmonary artery instead of the pulmonary trunk. It also shows a left a. Continuation of MPA as RPA without normal origin of
sided ligamentum arteriosum connecting the left pulmonary artery to
the descending aorta. LPA = Left pulmonary artery; PT = Pulmonary LPA in parasternal short axis view. The other differential
trunk; RPA = Right pulmonary artery. Courtesy: Reprinted with diagnosis of this are absent LPA and aberrant origin of LPA
permission from reference 1 from descending aorta. However, on tracing the RPA, the
LPA in this case can be demonstrated to arise from the RPA
(Figure 16).
b. Associated cardiac anomalies are diagnosed.
clinical manifestations
Pulmonary arterial sling often presents within infancy, more Cardiac Catheterization and Angiography
among males with obstructive respiratory symptoms like
stridor, wheezing and cough. Symptoms due to esophageal Although sparingly used now-a-days, this was a gold standard
compression are less common. in past. Angiography with injection of radiocontrast in
a B
Figures 15a and B: The chest X-ray is compared with computed tomography (CT) thorax in a child with pulmonary arterial sling. Careful
observation shows two levels of tracheal bifurcation in the chest X-ray and confirmed in CT. The airway has two levels of bifurcations in the
mediastinum, with a narrow intermediary segment, characteristic of congenital stenosis due to complete cartilaginous rings. The arrows indicate
the narrowed vertical segment of the trachea between its upper and lower bifurcations. Courtesy: Reprinted with permission from reference 1
538
36
MPA in a steep oblique view with cranial angulation of 60º of tracheobronchial involvement and efficacy of the surgery
to 70º elucidates the origin and course of anomalous LPA done. Postoperatively, it is used to assess the tracheal surgery,
(Figure 17).38 cause of endotracheal tube bleeding, cause of prolonged
ventilation etc.33
Computed Tomography with Three-Dimensional
Reconstruction management of Pulmonary Arterial sling
Computed tomography with three-dimensional reconstruction Medical
is especially important for all suspected cases of ring-sling
complex as it beautifully demonstrates both the vascular a. General supportive care and treatment of chest infections.
and airway abnormalities. It guides the surgeon to plan b. Symptomatic children should undergo surgical correction
the appropriate surgical therapy (Figure 18). Furthermore, without delay.29,39
complications of the pulmonary parenchyma like collapse-
consolidation, hyperinflation etc. can also be assessed. Surgical
Magnetic Resonance Imaging In 1954, Willis Potts reported the first surgical repair for
pulmonary arterial sling from children’s hospital, Chicago.
Magnetic resonance imaging (MRI) is probably less useful a. The surgical repair involves division and mobilization of
than CT in this respect as it is time-consuming, requires LPA from its origin in RPA and reimplantation of the LPA
sedation and anatomical details of airways and lungs are not into MPA and resection of all ductal tissue (Figure 19A).
elucidated as good as CT here. The usual approach is through median sternotomy and
after establishment of cardiopulmonary bypass.40,41
Bronchoscopy b. The tracheal stenosis also needs to be corrected if more
than mild in severity. The various approaches are:
In many centers, a preoperative bronchoscopy is part of the i. Short segment tracheal stenosis: Simple resection and
investigational protocol. Often external imaging of the trachea end-to-end anastomosis.
may not show internal abnormalities like complete rings. ii. Long segment stenosis: Tracheoplasty using a part of
Bronchoscopy informs us about the level, length and degree rib cartilage or pericardial patch (Figure 19B). In a
of luminal narrowing and allows precise surgical planning. long trachea, a piece of narrow segment from trachea
Also intraoperatively, it allows the surgeon to gauge the extent is resected and then the same segment can be used to 539
http://vip.persianss.ir
7
Diseases oF the aorta
Postoperative Course
The success of surgery depends not only on the vascular
anastomosis made, but also on severity of preoperative airway
obstruction. Persistent airway obstruction, hemorrhage,
infections, edema and stenosis are usually seen in perioperative
period. In severe cases, the airway symptoms may persist even
1 year after surgery due to pre-existing tracheomalacia. This
fact needs to be discussed with the parents before surgery.
Rare postoperative complications include chylothorax and
vocal cord palsy secondary to recurrent laryngeal nerve damage.
The postoperative mortality rates are variable and mostly
caused by associated tracheal and bronchial abnormalities.
Survivors usually are free of significant symptoms in long-term
follow-up. However, they need to be monitored for stenosis Figure 19B: This schematic diagram shows the pericardial tracheo-
of reimplanted LPA. Marmon et al studied 17 asymptomatic plasty technique. The trachea is opened anteriorly through the area
of complete tracheal rings. On cardiopulmonary bypass support,
patients at a mean 6.1 years after surgery.25 No correlation was the trachea is patched with autologous fresh pericardium anchored
found between age of diagnosis and surgery, type of vascular with interrupted sutures. Courtesy: Reprinted with permission from
lesion, or severity of presenting symptoms and abnormal reference 29
pulmonary function test. More long-term data is desirable,
using objective quantification of respiratory function, before
confirming the eventual curative nature of surgery.
arch far on the left side of midline and then courses to the
otHEr cAusEs oF VAsculAr comPrEssIon right and thus compresses the anterior wall of trachea. This
oF AIrWAys42,43 produces respiratory symptoms from stridor, cyanosis and
bradycardia. However, the symptoms are noted only if there is
a coexisting crowded superior mediastinum, either secondary
brachiocephalic Artery compression of Airways
to cardiomegaly or dilated vessels, etc. The treatment in severe
540 Brachiocephalic artery compression of airways is a condition, cases involves surgical suturing of brachiocephalic artery to
where the brachiocephalic artery arises from the aortic sternum (Figures 20A and B) .
36
Absent Pulmonary Valve syndrome compresses the right pulmonary artery, which in turn presses
This entity, most commonly associated with TOF, is associated on the left and right main bronchus (Figure 21).
with aneurysmally dilated pulmonary arteries, which exert
direct mechanical compression of tracheobronchial tree. In Elongated Aortic Arch
addition, the tracheobronchial tree is often inherently abnormal
including abnormal branching pattern, abnormal alveolar The classic example is right aortic arch in congenitally
architecture, etc. Surgical correction includes not only an corrected transposition. Here, the ascending aorta is
intracardiac repair but also plication and anterior translocation L-posed and ascends to the left and then takes a long
of pulmonary arteries. transverse course in front of trachea to connect to the
descending aorta in the right posterior mediastinum. Once
Posteriorly displaced Ascending Aorta the lungs are hyperinflated, they extend to the midline
behind sternum, pushing the mediastinal structures and
In this situation, the displaced ascending aorta may directly heart backward, further compromising the tracheal and
compress on the right side of trachea.The posterior aorta also bronchial patency.
Figure 20B: This computed tomography angiogram shows brachiocephalic (innominate) arterial compression of trachea. The compression is
at the level of inlet of thoracic cage and is located at a much higher level than that caused by double aortic arch or right arch with aberrant left 541
subclavian artery. The white arrow shows the brachiocephalic artery, the black arrow shows the trachea and the white overhead shows the es-
ophagus. Courtesy: Reprinted from Oddone M, et al. Multi-modality evaluation of the abnormalities of the aortic arches in children: techniques
and imaging spectrum with emphasis on MRI. Pediatr Radiol. 2005;35:947-60
http://vip.persianss.ir
7 development of human and mammalian embryos have never
been documented.
Diseases oF the aorta
a B
Figures 22a and B: The echocardiogram of the aortic arch in suprasternal view. A. Shows the double-barreled aorta in which an aortic arch
542 with dual lumen is found on the same side of trachea, in contrast to a double aortic arch. The computed tomography angiogram with 3D
reconstruction; B. Shows the same anatomy. The superior arch is atretic distal to the origin of left subclavian artery. (Courtesy: Reprinted with
permission from reference 1)
36
rEFErEncEs
http://vip.persianss.ir
7 9. Stewart JR, Kincaid OW, Edwards JE. An atlas of vascular
rings and related malformations of the aortic arch system.
27. Midulla PS, Dapunt OE, Sadeghi AM, et al. Aortic dissection
involving a double aortic arch with a right descending aorta.
Springfield, IL: Charles C Thomas; 1964. Ann Thorac Surg. 1994;58:874-5.
Diseases oF the aorta
10. Kommerell B. Verlagerung des osophagus durch eine abnorm 28. Dodge-Khatami A, Tulevski II, Hitchcock JF, et al.Vascular
verlaufende arteria subclavia dextra (arteria lusoria). Fortschr rings and pulmonary arterial sling: from respiratory collapse
Geb Roentgenstr. 1936;54:59. to surgical cure, with emphasis on judicious imaging in the hi-
11. Hastreiter AR, D’Cruz IA, Cantez T, et al. Right-sided aorta. I. tech era. Cardiol Young. 2002;12:96-104.
Occurrence of right aortic arch in various types of congenital 29. Backer CL, Mavroudis C, Rigsby CK, et al. Trends in vascular
heart disease. II. Right aortic arch, right descending aorta, and ring surgery. J Thorac Cardiovasc Surg. 2005;129:1339-47.
associated anomalies. Br Heart J. 1966;28:722-5. 30. Potts WJ, Holinger PH, Rosenblum AH. Anomalous left
12. Mustard WT, Trimble AW, Triusler GA. Mediastinal vascular pulmonary artery causing obstruction to right main bronchus:
anomalies causing tracheal and esophageal compression and report of a case. JAMA. 1954;155:1409-11.
obstruction in childhood. Can Med Assoc J. 1962;87:1301-5. 31. Glaevecke H, Doehle W. Ueber eine seltene angeborene.
13. Berman W Jr, Yabek SM, Dillon T, et al. Vascular ring due Anomalie der Pulmonarterie. Munch Med Wochenschr.
to left aortic arch and right descending aorta. Circulation. 1897;44:950.
1981;63:458. 32. Contro S, Miller RA, White H, et al. Bronchial obstruction due
14. van Son JA, Bossert T, Mohr FW. Surgical treatment of to pulmonary artery anomalies. I. Vascular sling. Circulation
vascular ring including right cervical aortic arch. J Card Surg. 1958;17:418.
1999;14:98. 33. Berdon WE, Baker DH, Wung JT, et al. Complete cartilage-ring
15. Nadas AS, Fyler DC. Pediatric cardiology. Philadelphia: WB tracheal stenosis associated with anomalous left pulmonary
Saunders; 1972. p.749. artery: the ring-sling complex. Radiology. 1984;152:57.
16. Godtfredsen J, Wennevold A, Efsen F, et al. Natural history of 34. Dodge-Khatami A, Tsang VT, Roebuck DJ, et al. Management
vascular ring with clinical manifestations. A follow-up study of congenital tracheal stenosis: a multidisciplinary approach.
of eleven unoperated cases. Scand J Thorac Cardiovasc Surg. Images Paediatr Cardiol. 2000;2:30-40.
1977;11:75. 35. Idriss FS, DeLeon SY, Ilbawi MN, et al. Tracheoplasty with
17. Backer CL, Mavroudis C. Surgical approach to vascular rings. pericardial patch for extensive tracheal stenosis in infants and
In: Karp RB, Laks H, Wechsler AS (Eds). Advances in Cardiac children. J Thorac Cardiovasc Surg. 1984;88:527-36.
Surgery. Chicago Mosby Year Book; 1997. pp.9:29-64. 36. Mitchell JH, Austin EH III. Vascular rings, slings, and other
18. Arciniegas E, Hakimi M, Hertzler JH, et al. Surgical arch anomalies. In: Kaiser, Kron, Spray (Eds). Mastery of
management of congenital vascular rings. J Thorac Cardiovasc Cardiothoracic Surgery. Philadelphia; Lippincott-Raven, 1998,
Surg. 1979;77:721-7. pp. 663-76.
19. Woods RK, Sharp RJ, Holcomb GW III, et al. Vascular anomalies 37. Newman B, Cho YA. Left pulmonary artery sling—anatomy
and tracheoesophageal compression: a single institution’s 25- and imaging. Semin Ultrasound CT MR. 2010;31(2):158-70.
year experience. Ann Thorac Surg. 2001;72:434-9. 38. Freedom R, Culham J. The Angiography of Congenital Heart
20. Berdon WE. Rings, slings, and other things: vascular compres- Disease. 1998.
sion of the infant trachea updated from the midcentury to the 39. Grover FL, Norton JB Jr, Webb GE, et al. Pulmonary sling.
millennium—the legacy of Robert E Gross, MD and Edward Case report and collective review. J Thorac Cardiovasc Surg.
BD Neuhauser, MD. Radiology. 2000; 216:624-32. 1975;69(2):295-300.
21. Allen HD, Goldberg ST, Sahn DJ, et al. Suprasternal notch 40. Fiore AC, Brown JW, Weber TR, et al. Surgical treatment of
echocardiography: assessment of its clinical utility in pediatric pulmonary artery sling and tracheal stenosis. Ann Thorac Surg.
cardiology. Circulation. 1977;55:605. 2005;79:38-46.
22. Abnormal vascular connections and structures. In: Snider AR, 41. Backer CL, Mavroudis C, Dunham ME, et al. Pulmonary artery
Serwer GA, Ritter SB (Eds). Echocardiography in Pediatric sling: results with median sternotomy, cardiopulmonary bypass,
Heart Disease. 2nd edition. 1999 Mosby year book, 452-96. and reimplantation. Ann Thorac Surg. 1999;67:1738-44.
23. Murdison KA, Andrews BA, Chin AJ. Ultrasonographic dis- 42. Kim YM, Yoo SJ, Kim TH, et al. Tracheal compression by
play of complex vascular rings. J Am Coll Cardiol. 1990;5: elongated aortic arch in patients with congenitally corrected
1645-53. transposition of the great arteries. Pediatr Cardiol. 2001;22:471-7.
24. Oddone M, Granata C, Vercellino N, et al. Multi-modality 43. Kim YM, Yoo SJ, Kim WH, et al. Bronchial compression
evaluation of the abnormalities of the aortic arches in children: by posteriorly displaced ascending aorta in patients with
techniques and imaging spectrum with emphasis on MRI. congenital heart disease. Ann Thorac Surg. 2002;73:881-8.
Pediatr Radiol. 2005;35:947-60. 44. Bernasconi A, Goo HW, Ypp SJ. Double-barrelled aorta with
25. Hernanz-Shulman M. Vascular rings: a practical approach to tetralogy of Fallot and pulmonary atresia. Cardiol Young.
imaging diagnosis. Pediatr Radiol. 2005;35:961-79. 2007;17:98-101.
26. Marmon LM, Bye MR, Haas JM, et al. Vascular rings and 45. Sun A, Alhabshan F, Branson H, et al. MRI diagnosis of isolated
slings: long-term follow-up of pulmonary function. J Pediatr origin of the left subclavian artery from the left pulmonary
Surg. 1984;19:683-92. artery. Pediatr Radiol. 2005;35:1259-62.
544
Sec t i on
http://vip.persianss.ir
C hapter
37 Tetralogy of Fallot
http://vip.persianss.ir
8 Box 1A: Pulmonary valve configuration Box 1E: Associated anomalies
in patients with tetralogy of Fallot in tetralogy of Fallot5
Cyanotic Heart diseases
Clinical features
anomalies and monogenic syndromes. Chromosomal anomalies
History
are involved in about 12 percent of the cases, e.g. trisomy 21
548 (Down syndrome), trisomy 13 (Patau syndrome) and trisomy 18 Tetralogy of Fallot is slightly more common in males than
(Edwards syndrome). Advances in cytogenetic and molecular in females.7 Patients with TOF most often present in infancy
with cyanosis due to right to left shunting of blood at the
Box 2A: Mechanism of cyanotic spells
37
level of the VSD.8 The degree of right ventricular outflow
tract obstruction (RVOTO) often correlates with the degree
Tetralogy of Fallot
of cyanosis and the timing of presentation. Thus patients
with mild pulmonary obstruction present late, perhaps even
in adulthood, the so-called “pink TOF”, while patients with
severe obstruction may present soon after birth on closure of
the ductus arteriosus.8,9 In less severe cases, cyanosis is first
noticed during crying.
Cyanotic spell is an important manifestation of TOF. The
tachycardia, immature vulnerable respiratory center and
dynamic subpulmonary obstruction is believed to be a major
factors behind the origin of the hypercyanotic spells. The
other important contributor being variations in the systemic
vascular resistance (SVR). The mechanism of spell is shown in
Box 2A and the various theories of mechanism of spell is
shown in Box 2B.10-13 Spell usually occurs in infants between
3 to 24 months of age.8,9 Typical spell is characterized by
progressive increase in the rate and depth of respiration, Box 2B: Theories for explanation of mechanisms
deepening cyanosis, limpness or syncope. Convulsions, of cyanotic spells10-13
cerebrovasclur accident and death are potential complications. A. Wood's theory: Postulated that hypoxemic spells are
Spells are less common after 2 years. Initiated usually by caused by spasm of the infundibulum of the right ventricle
crying, feeding or bowel movement, spells are particularly which precipitates a cycle of progressively increasing right to
common after getting up from sleep. It is postulated that a left shunting and metabolic acidosis.
vulnerable respiratory center, which is particularly sensitive B. Catecholamine release: Leads to increased myocardial
after prolonged sleep, reacts to sudden increase in cardiac contractility and infundibular stenosis (both these theories
output provoked by feeding, crying or straining to initiate do not explain the cause of cyanotic spells in patients with
tetralogy of Fallot with pulmonary atresia).
the vicious cycle of spell. Such actions lead to increased
venous return to the right heart. In presence of obstruction C. Guntheroth's theory: Episodes of paroxysmal hyperpnoea
are the cause rather than the effect of cyanotic spells.
to pulmonary flow, right to left shunt increases. This right Hyperpnoea increases the systemic venous return leading
to left shunt leads to acidosis, which in turn stimulates the to right to left shunt as well as oxygen consumption through
respiratory center, provoking hyperpnea, further worsening increase work of breathing.
systemic oxygen saturation. A vicious cycle of progressive D. Kothari's theory: Argued against the other hypotheses
hypoxia, acidosis and hyperpnea ensues. Infundibular spasm and suggested the role of stimulation of mechanoreceptors in
secondary to increased sympathetic tone aggravates the the right ventricle to be the cause of spells.
problem by increasing right to left shunt. The drop in SVR E. Morgan’s theory: Vulnerable respiratory centre which
with muscular activity is a major contributor to right to left over-reacts to hypoxic stimuli like crying, feeding causes
shunt. an increase in cardiac output and heart rate which in turn
increases venous return causing an increase in right to left
Exertional dyspnea is common in the older child. A shunt across the ventricular septal defect which leads to a fall
characteristic posture older children with TOF assume to in PaO2 and increase in PCO2. The respiratory centre over-
increase pulmonary blood flow and to alleviate dyspnea is reacts to this stimulus and causes hyperpnea which again
squatting. Squatting is of diagnostic significance in TOF. increases the venous return, thereby causing a vicious cycle.
Squatting increases peripheral vascular resistance and thus F. Young’s theory: It was proposed that the spell was
decreases the magnitude of the right to left shunt across the precipitated by an atrial tachycardia.
VSD. Locking up the more desaturated lower limb venous
blood and displacing the better oxygenated mesenteric
venous blood into the right heart may be the other benefits Clinical Examination
of squatting. Exertional dyspnea usually worsens with age.
Occasionally, hemoptysis may occur in the older child due Most infants are smaller than expected for age. Cyanosis of
to rupture of bronchial collaterals. RV failure is uncommon the lips and nail bed may be noticed at birth or may appear
in TOF patients but the various circumstances in which the later. Cyanosis in TOF is determined by the severity of
patient can present with RV failure are given in Box 3 pulmonary stenosis and also to a lesser extent by systemic
549
http://vip.persianss.ir
8 Box 3: Causes of right ventricular failure
in 6.7 percent. A reticular pattern in the lung fields due to
in tetralogy of Fallot bronchial collaterals was seen in 23.1 percent. The incidence of
right aortic arch (19.9%), absent left pulmonary artery (2.8%),
Cyanotic Heart diseases
1. Pulmonary atresia with large systemic arterial collaterals absent right pulmonary artery (0.7%) and dextrocardia (1.4%)
2. Accessory tricuspid leaflet tissue partially occluding the is brought out. The right atrial mean pressure was increased
ventricular septal defect making it restrictive and causing in 4.8 percent and a prominent “a” wave greater than 10
supra systemic right ventricular pressure.
mm Hg was present in 10.9 per cent. The right ventricular
3. Absence of pulmonary valve causing combination of
end-diastolic pressure was increased in 23.8 percent and the
stenosis (annular narrowing) and free pulmonary
regurgitation. left ventricular end-diastolic pressure in 25.9 percent of the
4. Systemic hypertension
patients.This study clearly shows that a lot of clinical features
which are usually considered uncharacteristic in TOF patients
5. Acquired calcific aortic stenosis or regurgitation of the
biventricular aortic valve can be present in adult uncorrected TOF patients.14
6. Infective endocarditis affecting the aortic valve
7. Hyperdynamic circulatory status like due to anaemia, Chest X-Ray
thyrotoxicosis
Plain films may classically show a "boot shaped" heart with
8. Adult tetralogy of Fallot with aortic regurgitation
an upturned cardiac apex due to right ventricular hypertrophy
and concave pulmonary arterial segment. Lung vascularity is
decreased (Figures 1A and B ). A right aortic arch is present
to pulmonary collaterals. Infundibular stenosis worsens as in 25 percent.15
the infant grows so that a previously pink baby turns blue.
In the case of pulmonary atresia, cyanosis sometimes may be Electrocardiogram
absent due to systemic pulmonary collaterals. Clubbing may
be present after 3 months of life. General examination may Right ventricular hypertrophy and right axis deviation are the
reveal subtle features of 22q11 microdeletion. Precordium salient features of TOF. Older children and adults may show
is quiet. S1 is normal, while S2 is single due to a faint right atrial enlargement. Whereas the R wave in V1 is tall and
P2. Delayed and hesitant closure of the pulmonary valve usually monophasic, R wave in V2 is much shorter – the so
due to the slow pressure drop in the stenotic infundibular called “sudden transition” is characteristic (Figure 2). In patients
chamber, associated valvar stenosis and the overrding aorta with pulmonary stenosis and restrictive VSD, right precordial
all contribute to the single S2. A prominent ejection systolic leads show deeply inverted T waves in right precordial leads.16
murmur, is heard at the mid and upper left sternal border. Left axis deviation denotes an inlet VSD.
The intensity of this murmur is inversely proportional to the
severity of stenosis. With more severe stenosis RV pumps Echocardiography
more into the aorta and less across the RVOT, decreasing the
murmur. The murmur disappears during a spell. An aortic Echocardiography allows examination of all essential features
ejection click due to the dilated ascending aorta may be heard of tetralogy of Fallot and has a crucial role in diagnosis
over the apex. A continuous murmur below the left clavicle and preoperative evaluation (Figures 3A and B). Complete
denotes a patent ductus arteriosus (PDA). A more widely echocardiographic evaluation usually obviates the need for
heard continuous murmur, especially over the back, is due to further imaging. Most of the information can be achieved
systemic-pulmonary collaterals. with transthoracic echocardiography, but occasionally trans
esophageal echocardiography may be helpful for specific
Adult TOF questions raised by transthoracic echocardiography. A
complete study must address:
A large group of TOF patients are seen to survive to adulthood 1. The location and number of VSDs
without surgical correction and with the vast prevalence of 2. The anatomy and severity of RVOTO (Figures 4A and B).
TOF the number of such patients presenting to a clinician The size and anatomy of the main pulmonary artery, the
is increasing. Some of the studies have addressed the basic pulmonary arterial confluence, and the proximal branch
difference in the pathophysiology and the presentation of these pulmonary arteries, as far distally as possible, must be
patients. The largest study on adult TOF patients was done by demonstrated.
Abraham et al in which he evaluated the presentation of 147 3. The coronary arteries must be imaged, specifically looking
patients, above the age of 18 with TOF. Cardiac catheterization for any major branch crossing the RVOT. The LAD arises
and selective cine angiography were performed in all. Cardiac from the RCA and crosses the RVOT in 5 percent.
enlargement was seen in 25.8 percent of the patients, and 15.6 4. Aortic arch laterality must be shown. The presence of
550 percent were in congestive cardiac failure; 9.5 percent had any associated anomalies like atrial septal defect PDA,
systemic hypertension, and aortic regurgitation was present additional VSDs must also be looked for.
37
Tetralogy of Fallot
A B
Figures 1A and B: Chest X-ray in Tetralogy of Fallot (TOF): A. Classical boot-shaped heart with right sided aortic arch oligemia with empty
pulmonary bay; B. TOF with collaterals showing the reticular lacy appearance in the lung fields with right sided aortic arch.
Figure 2: Electrocardiography in tetralogy of Fallot shows right-axis deviation, tall R wave in V1, with sudden transition in V2 with deep S wave
Cardiac catheterization
Cardiac catheterization may be necessary in few cases to
further delineate the levels of right ventricular outflow
obstruction, branch pulmonary artery stenosis or hypoplasia,
coronary artery anatomy, presence of aortopulmonary colla
terals, and presence of additional VSD. The findings on
oximetry in patients with TOF is given in Box 4.
The hemodynamic findings at catheterization typically
reveal normal or only mildly elevated filling pressures. The left
and right ventricular systolic pressures are equal. Pulmonary
artery pressures are normal or low. The degree of right-to-left
A B shunting is best shown by the degree of systemic desaturation.
Angiographic assessment should be geared towards the
Figures 3A and B: Echocardiography in tetralogy of Fallot. A. Five-
information that is needed; biplane angiography is ideal. 551
chamber view shows large ventricular septal defect (VSD), overriding
of the aorta; B. Bidirectional shunt across the VSD. RV angiogram (anteroposterior [AP] cranial, shallow
http://vip.persianss.ir
8 Box 4: Salient features of oximetry run
in tetralogy of Fallot
Cyanotic Heart diseases
B
Figures 4A and B: A. Short-axis view showing infundibular stenosis
with turbulence; B. Right ventricle outflow tract gradient on Doppler is
81 mm Hg.
Tetralogy of Fallot
Nakata index: Sum of the cross sectional areas of the left and may diminish the increase in pulmonary vascular
and right pulmonary arteries at their prebranching points
as related to body surface area. The normal Nakata index
resistance caused by hypoxia and acidosis. It can be
is + 330 mm2 /m2. An index of more than 150 mm2 /m2 is repeated in 10-15 minutes.
acceptable for complete repair without prior palliative shunt. 6. Beta blockers like injection propanolol is given in
Tetralogy of Fallot with pulmonary stenosis should have an a dose of 0.1-0.2 mg/kg IV over 5 minutes and can
index of more than 100 for surgery. be repeated once after 15 minutes. It decreases the
McGoon ratio: Ratio of the sum of the pre branching heart rate, infundibular spasm and increases SVR. If
diameters of the left and right pulmonary arteries to the propanolol is not available then injection metoprolol
diameter of the descending aorta just above the level of the
can be given in a dose of 0.1 mg/kg over 5 minutes.
diaphragm. Ratio above 1.2 is associated with acceptable
postoperative right ventricular systolic pressure in tetralogy of Another short acting beta blocker which can be given is
Fallot. injection esmolol in a dose is 0.5 mg (500 mcg)/kg over
Z-Score: The branch pulmonary artery diameter Z-score is the 1 minute and then as an infusion of 50 to 200 mcg/kg/
most important determinant of surgical strategy, with the worst min up to 48 hours.
figures being associated with no surgical options or palliative 7. In refractory cases vasopressors can be given to
surgery and the best figures leading to corrective surgery increase the SVR and promote the redirection of blood
Z = Observed dimension - Mean normal dimension/standard deviation flow through the pulmonary circulation. Phenylephrine
around mean normal dimension a alpha-adrenergic blocker can be given in a dose of 5 to
20 mcg/kg IV bolus, followed by an infusion of 0.1 to
0.5 mcg/kg/min.
correction is done. A cyanotic spell is usually self limiting and 8. Avoid any actions that agitate the baby like vigorous
lasts less than 15-30 minutes. examination, repeated attempts to venipuncture etc.
But sometimes they can be prolonged and require The drugs to be avoided are inotropes (e.g. digoxin,
emergency measures like: dopamine, or dobutamine) and diuretics.
1. Hold the child in knee chest position.This increases the 9. If the spell is persistent or refractory, then intubation
SVR and decreases the desaturated systemic venous and mechanical ventilation maybe required.
return. 10. A emergency Blalock-Taussig (BT) shunt / pulmonary
2. Calm the child. The ideal sedative is morphine. It causes balloon valvuloplasty (PBV) may be required in
respiratory centre suppression and sedation thereby refractory cases.
reducing hyperpnea. It reduces the ventilatory drive and The stepwise approach for management of TOF patient
decreases systemic venous return (venodilator). This who present in a cyanotic spell is given in Box 6.
will decrease the release of catecholamines, increase
the period of right ventricular filling by decreasing CATHETER INTERVENTIONS IN TOF
the heart rate and relax the infundibulum. The dose of
morphine is 0.1 mg/kg and it can be given intravenous Catheter based interventions can identify and apply the
(IV), intramuscular (IM) or subcutaneous. It may be most effective but least invasive solutions to most difficult
repeated after 5 minutes. The ventilation facilities pathologies of TOF. Interdisciplinary approach can decide
should be at hand. The other alternative sedatives on the best approach and combine interventional and surgical
are: midazolam 0.05–0.1 mg/kg (IV, intranasal or alternatives for the best possible outcome resulting in fast
intrarectal) or dexmedetomidine 0.5 -1 mcg/kg IV or recovery, significantly reduce morbidity and mortality over
infusion of 0.2 mcg/kg/hr or fentanyl 1–2 mcg/kg IV. traditional surgery.
Ketamine has dual benefit of causing sedation and The various transcatheter interventions in TOF are:
increasing SVR. The dose is 0.25- 1.0 mg/kg IV or IM. 1. Balloon dilatation of pulmonary stenosis.
3. 100% Oxygen supplementation. This causes pulmonary 2. Balloon dilatation and/or ductal stenting.
vasodilation and hence decreases the pulmonary 3. The coil closure of MAPCAs (Figures 6A and B).
vascular resistance (PVR). The least aggravating 4. Balloon dilatation of peripheral pulmonary artery stenosis
method of delivery should be used. with or without stenting.
4. Establish immediate IV access to allow prompt 5. Balloon dilatation of blocked BT shunt.
administration of fluids, which will improve right 6. Stenting of RVOT for infundibular stenosis by
ventricular preload. Initially, fluid is given as a bolus of balloon expandable stainless steel stents (Johnson &
10-20 cc/kg, which may be increased to 60cc/kg. Bolus Johnson).
fluid should be isotonic saline or colloid. 7. Transcatheter pulmonary valve replacement. 553
http://vip.persianss.ir
554
8
Cyanotic Heart diseases
Tetralogy of Fallot
A B
Figures 6A and B: A. Selective angiogram in postoperative tetralogy of Fallot patient who
presented with hemoptysis and hypotension, shows multiple collaterals; B. Fluoroscopy shows
multiple Gianturco embolization coils (small arrows) along with sternal suture wires
http://vip.persianss.ir
8
Cyanotic Heart diseases
A B
Figures 7A and B: A. The pulmonary angiogram shows tight stenosis of left pulmonary artery (arrow);
B. The check angiogram after the balloon dilatation illustrates no stenosis
A B C
Figures 8A to C: A. Selective angiogram of left subclavian artery shows the stump of blocked Blalock-Taussig (BT) shunt (arrow); B. 4X30
balloon across the BT shunt (arrow); C. Selective angiogram of the reopened functional BT shunt illustrates good flow into left pulmonary artery
(LPA) in a one and half year old child of dextrocardia with tetralogy of Fallot. The saturations improved dramatically from 48 to 82 percent
some potential morbidity and mortality, many centers have Long-Term Follow-up
reported excellent outcome with this approach.21-23 The Patients with repaired TOF have the potential to lead normal
various contraindications to performing an intracardiac repair lives with excellent cardiac function. Most survivors are in
are given in Box 8. The various palliative procedures which New York Heart Association (NYHA) Class I or II. Some
can be performed in TOF patients to augment the pulmonary patients have more symptoms on exertion. 90 percent of
blood flow are given in Box 9. The difference between classic patients with total repair develop progressive pulmonary
and modified BT shunt has been discussed in Box 10. regurgitation (PR). Patients also may have some degree
of residual RVOTO and damage to the conduction system
Natural History of the heart. The incidence of bradyarrhythmias after
TOF repair has been drastically reduced in recent years.
If left untreated, TOF results in progressive right ventricular The incidence of late atrial arrhythmias after TOF repair
hypertrophy and right ventricular dilatation and threatens is relatively high, about 30 percent, including atrial
survival. If pulmonary atresia is present as well, survival is fibrillation, flutter, focal or reentrant atrial tachycardia.25
even poorer with only 50 percent of patients surviving to 1 Therefore, lifetime surveilance is recommended to assess
year and only 8 percent of patients surviving to 10 years. and monitor these risks and to recommend treatment. TOF
556 Survival without treatment is given in Box 11. patients are at risk for sudden cardiac death with 1 to 5
Box 7: Surgical techniques Box 9: Palliative procedures augmenting 37
for intracardiac repair pulmonary blood flow
Tetralogy of Fallot
1. Transventricular approach: This was the earliest • Blalock-Taussing shunt (classical): Subclavian artery to
approach which was used for RVOT resection but fell into pulmonary artery anastomosis (end-to-side). Infrequently, this
disrepute due to the high incidence of ventricular arrhythmias, may lead to pulmonary hypertension.
conduction system defects and right ventricular dysfunction. • Blalock-Taussing shunt (modified): Interposition graft
This difference from other surgical approaches has been between subclavian artery and ipsilateral pulmonary artery.
proven in various follow up studies. Controlled augmentation of pulmonary blood flow. Usually
2. Transatrial approach: The transatrial approach for a 4mm Gore-Tex shunt is required early in infancy. Larger
tetralogy of Fallot repair was proposed by Hudspeth et al24 shunts would be required for older patients, although the
in 1963. This method has significant advantages as over the possibility of repair should always be explored first.
transventricular approach for intracardiac repair. The salient • Waterston shunt: Ascending aorta-to-main or right
features of this method are: pulmonary artery (side-by-side). No artificial material
• Preservation of ventricular function used; shunt grows with the patient. May lead to pulmonary
• Decreased severity of PR hypertension. Infrequently, problems have been encountered
with pulmonary artery disruption, requiring extensive
• No risk of injuring branches of RCA arterioplasty.
• No scar on ventricle • Potts shunt: Descending aorta-to-left pulmonary artery
• Decreased arrhythmias (side-by-side). Frequent complication with narrowing
• Adequate annulus is a must and kinking of the left pulmonary artery at the site of the
anastomosis. The latter necessitates reconstructive surgery
3. Combined transatrial and transpulmonary approach:
during repair, occasionally through an additional thoracotomy,
The salient features of this approach are:
which made this shunt unpopular.
• Small ventriculotomy
• Central interposition tube graft: A Gore-Tex graft is often
• Minimizes RV dysfunction used for patients not suitable for early repair.
• Excellent exposure • Infundibular resection (Brock procedure) or closed
• Lower RVEDP, higher RVEF during isoprenaline infusion pulmonary valvotomy: Often effective palliative procedure
• Lower incidence of ventricular arrhythmias from an earlier surgical era.
• Suitable for all patients • Relief of RVOT obstruction without VSD closure or with
fenestrated VSD closure: In patients with multiple pulmonary
PR = Pulmonary regurgitation; RCA = Right coronary artery; RV = Right artery stenoses or hypoplasia.
ventricle; RVEDP = Right ventricle end diastolic pressure; RVEF = Right
ventricle ejection function; RVOT = Right ventricular outflow tract RVOT = Right ventricular outflow tract; VSD = Ventricular septal defect
http://vip.persianss.ir
8 Box 10: Classic v/s modified Blalock-Taussig shunt Box 11: Survival without treatment in patients
with tetralogy of Fallot
Cyanotic Heart diseases
Tetralogy of Fallot
5th edition. Philadelphia, Pa.: Saunders; 2006. Hijazi Z (eds). Informa UK Ltd. 2007. 197-200.
2. Van Praagh R, Van Praagh S, Nebesar RA, et al. Tetralogy of 19. Alekian BG, Petrosian IuS, Podzolkov VP et al. Catheter
Fallot: Underdevelopment of the pulmonary infundibulum and therapy of congenital cardiovascular defects. Vestn Rentgenol
its sequelae, report of a case with cor triatriatum and pulmonary Radiol. 1995;2:16-26.
sequestration. Am J Cardiol. 1970;26:25-33. 20. Karl TR, Sano S, Pornviliwan S, et al. Tetralogy of Fallot:
3. Van Mierop LHS. Developmental aspects of tetralogy of Fallot. Favorable outcome of nonneonatal transatrial, transpulmonary
Singapore Med J. 1973;14:166-68. repair. Ann Thorac Surg. 1992;54:903-7.
4. Dabizzi RP, Caprioli G, Aiazzi L, et al. Distribution and 21. Gladman G, McCrindle BW, Williams WG, et al. The modified
anomalies of coronary arteries in tetralogy of Fallot. Blalock-Taussig shunt: Clinical impact and morbidity in
Circulation. 1980 ;61:95-102. Fallot's tetralogy in the current era. J Thorac Cardiovasc
5. Kirklin JW, Blackstone EH, Kirklin JK, et al. Surgical results Surg.1997;114:25-30.
and protocols in the spectrum of tetralogy of Fallot. Ann Surg 22. Stewart RD, Backer CL, Young L, et al. Tetralogy of Fallot:
1983;198:251-65. Results of a pulmonary valve-sparing strategy. Ann Thorac
6. MC Digilio. Genetic basis of tetralogy of Fallot - 2008. Surg. 2005;80:1431-38.
EUROGENE portal. Jan 2009. 23. Makaryus AN, Aronov I, Diamond J, et al. Survival to the
7. Starr JP. Tetralogy of Fallot: Yesterday and today. World J age of 52 years in a man with unrepaired tetralogy of Fallot.
Surg. 2010;34:658-68. Echocardiography. 2004;21:631-37.
8. Gatzoulis MA, Webb GD, Daubeney PEF, (Ed). Diagnosis and 24. Hudspeth AS, Cordell AR, Meredith JH, et al. An improved
management of adult congenital heart disease. 2nd edition. transatrial approach to the closure of ventricular septal defects.J
London: Churchill Livingstone; 2011. Thorac Cardiovasc Surg. 1962 Feb;43:157-65.
9. Wyszynski DF, Graham TP, Correa-Villasenor A (Eds). 25. Murphy JG, Gersh BJ, Mair DD, et al. Long-term outcome in
Congenital Heart Defects: From Origin to Treatment. Oxford patients undergoing surgical repair of tetralogy of Fallot. N
University Press, New York, 2010. Engl J Med. 1993;329:593-99.
10. Wood P. Attack Of Deeper Cyanosis And Loss Of Consciousness 26. Nollert G, Fischlein T, Bouterwek S, et al. Long-term survival
(Syncope) In Fallot’s Tetralogy. Br Heart Journal 1958;20:282- in patients with repair of tetralogy of Fallot: 36-year follow-up
6. of 490 survivors of the first year after surgical repair. J Am Coll
11. Guntheroth WG, Morgan BC, Mullins GL, Physiologic Studies Cardiol. 1997;30:1374-83.
Of Paroxysmal Hyperpnea In Cyanotic Congenital Heart 27. Norgaard MA, Lauridsen P, Helvind M, et al. Twenty-to-thirty-
Disease. Circulation 1965;31: 70-6. seven year follow-up after repair for tetralogy of Fallot. Eur J
12. Kothari S.S., Mechanism Of Cyanotic Spells In Cardiothorac Surg. 1999;16:125-30.
Tetralogy Of Fallot--The Missing Link?, Intl. Journal Of 28. Harrison DA, Harris L, Siu SC, et al. Sustained ventricular
Cardiology,1992;37:1-5. tachycardia in adult patients late after repair of tetralogy of
13. Young D, Elbl F. Supraventricular tachycardia as cause of Fallot. J Am Coll Cardiol. 1997:30;1368-73.
cyanotic syncopal attacks in tetralogy of Fallot. N Engl J Med. 29. Gatzoulis MA, Clark AL, Cullen S, et al. Right ventricular
1971;284:1359-60. diastolic function 15 to 35 years after repair of tetralogy
14. Abraham KA. Tetralogy of Fallot in adults. A report on 147 of Fallot: Restrictive physiology predicts superior exercise
patients. Am J Med. 1979;66:811-6. performance. Circulation. 1995;91:1775-81.
15. Siwik ES, Erenberg F, Zahka KG, Goldmuntz E. Tetralogy of 30. Cesnjevar R, Harig F, Raber A, et al. Late pulmonary valve
Fallot. In Allen HD, Driscoll DJ, Shaddy RE (Eds). Moss and replacement after correction of Fallot’s tetralogy. Thorac
Adams’ Heart Disease in Infants, Children, and Adolescents: Cardiovasc Surg. 2004;52:23-28.
Including the Fetus and Young Adults. Lippincott. Williams 31. Yemets IM, Williams WG, Webb GD, et al. Pulmonary valve
and Wilkins, Baltimore, MD 2008.pp 888-910. replacement late after repair of tetralogy of Fallot. Ann Thorac
16. Kasar PA, Ravikumar R, Varghese R, et al. Computed Surg 1997;64:526-30.
tomographic angiography in tetralogy of Fallot. Asian 32. Therrien J, Siu SC, McLaughlin PR, et al. Pulmonary valve
Cardiovasc Thorac Ann. 2011;19:324-32. replacement in adults late after repair of tetralogy of Fallot: Are
17. Karl TR. Tetralogy of Fallot: Current surgical perspective. Ann we operating too late? J Am Coll Cardiol. 2000;36: 1670-75.
Pediatr Cardiol. 2008;1:93-100.
559
http://vip.persianss.ir
C hapter
Pulmonary Stenosis
38 with Interatrial Communication
Vijayalakshmi IB
table 1
The differences between tetralogy and trilogy of Fallot.
Tetralogy Trilogy
1. Anatomy Non-restrictive VSD with overriding aorta Pulmonary valvar stenosis with PFO/
with anterocephalad deviation of outlet restrictive ASD with right to left shunt with
outlet septum with infundibular stenosis intact IVS
2. Cyanosis Occurs 2–3 month after birth, all cyanotic by Usually in late childhood, puberty or
5–8 years, even on rest adulthood, mild cyanosis appears on
exertion initially
11. Murmur Grade 3/6 ESM in third left ICS, intensity Grade > 3/6 loud, long ESM beyond
of murmur decreases with increase in A2 in second left ICS, TR murmur in RVF
infundibular stenosis
12. Ejection sound Eddy sounds may be heard Pulmonary EC may be heard
14. Chest X-ray Boot-shaped heart with RVH, no RAE, Oligemic lung fields with cardiomegaly,
oligemic lung fields, pulmonary bay empty, RAE, RVH, MPA prominent
right-sided aortic arch in 25%
561
Contd...
http://vip.persianss.ir
8 Contd...
Tetralogy Trilogy
cyanotic heart diseases
15. Cath and RV angiogram Shows simultaneous opacification of dilated Dilated RV with dysfunction, valvar
aorta and small pulmonary arteries, mainly stenosis, poststenotic MPA dilatation
infundibular stenosis
16. Management Blalock-Taussig shunt, Intracardiac repair PBV with or without ASD device closure/
surgery
ASD = Atrial septal defect; EC = ejection click; ECG = Electrocardiogram; ESM = Ejection systolic murmur; ICS = Intercostal space;
IVS = Interventricular septum; JVP = Jugular venous pulse; MPA = Main pulmonary artery; PBV = Pulmonary balloon valvuloplasty;
PFO = Patent foramen ovale; PSH- parasternal heave; RAD = Right axis deviation; RAE = Right atrial enlargement ; RV = Right
ventricle; RVF = Right ventricular failure; RVH = Right ventricular hypertrophy; TR = Tricuspid regurgitation; VSD = Ventricular septal
defect.
with upward convexity of the ST segments and deep S waves of R wave in V1 multiplied by 5 gives the transvalvar
in left precordial leads.16 In patients with true ASD, there is an gradient.
rsR′ or Rsr′ pattern17 (Figure 1).
eCHoCarDIograPHy
CHeSt raDIograPHy
The transthoracic 2D echocardiography (TTE) with continuous
The chest X-ray is similar to that of severe isolated PS. There wave Doppler and color flow is adequate for both the anatomic
is cardiomegaly due to RA and RV enlargement. The main and physiologic diagnosis. The TEE is similar to that in severe
pulmonary artery is dilated due to poststenotic dilatation. The PS. M-mode shows RVH with thick interventricular septum
chest X-ray in these patients are in an intermediate position (Figure 2). The systolic doming of the thickened pulmonary
between the small shadows of the pulmonary vessels in TOF valve can be visualized in the parasternal short-axis view.
and the very prominently dilated and congested pulmonary The continuous Doppler is used to assess the pulmonary
vessels of the Eisenmenger syndrome.4 The lung fields are valve gradient (Figure 3A). The subcostal four chamber view
oligemic and is more pronounced with RV failure. The RV shows interatrial septum bulging towards left atrium with a
apex is not boot-shaped as in TOF as the size of the left PFO or ASD (Figure 3B). The color flow imaging shows the
ventricle is not reduced16 and the pulmonary bay is not right-to-left shunt. Also one can assess RVH, RV function
empty. On fluoroscopy, “rocking boat” effect is seen in and the severity of TR. The pulmonary annulus, the size of
the anteroposterior view as first the RA, forming the right the ASD and its rims can be measured by TTE. This helps in
heart border, contracts forcefully and then the hypertrophied selecting the size of the balloon and device for non-surgical
RV, forming the left heart border, contracts. The height transcatheter management.
562
Figure 1: Electrocardiogram shows right axis deviation with right atrial and ventricular hypertrophy with rsR′ pattern in right precordial leads.
38
http://vip.persianss.ir
8 If PS is progressive, valve is dysplastic, and annulus is very with intact ventricular septum. A distinct hemodynamic-
morphologic syndrome. Chest. 1980; 78:759-62.
narrow, then the surgical valvotomy with transannular patch
with surgical closure of ASD is indicated. 10. Engle MA, Taussig HB. Valvular pulmonic stenosis with
cyanotic heart diseases
564
C hapter
http://vip.persianss.ir
8 • Stenosis of the systemic arterial channels – pulmonary
arteries may be hypoplastic.
Cyanotic Heart diseases
Interventricular Communication
The entire right ventricular output enters the systemic
circulation via the nonrestrictive malaligned ventricular
septal defect (VSD) roofed by the dilated aorta. It can be
perimembranous with a fibrous posteroinferior border or
A B C can extend to be doubly committed or juxta-arterial. It can
Figures 1A to C: Anatomy of ventricular outflow tract in pulmonary have entirely muscular borders, when the posteroinferior
atresia-ventricular septal defect (PA-VSD). A. Imperforate pulmonary limb of the septomarginal trabeculation fuses with the
valve or valvular atresia; B. Muscular atresia; C. Extreme form—
absence of pulmonary trunk
ventriculoinfundibular fold. The VSD can become restrictive
or may close because of the accessory tricuspid valve tissue,
in which case the hypertensive ventricle is hypertrophied with
reduced intracavitary volume.9,13
at the entrance to or at the distal end of the subpulmonary
infundibulum. The extreme form is represented by the Aorta
absence of all the intrapericardial pulmonary arteries. In
the most common pattern, the muscular outlet septum fuses The biventricular aorta is dilated and often continues as a
directly with the parietal musculature of the right ventricle, right aortic arch. It is related to the aorta receiving the entire
thus obliterating the ventriculo-pulmonary junction. In a cardiac output as well as to the inherent medial abnormality.
small number of cases, the atresia is found at the mouth of the The incidence of right aortic arch is as high as 50 percent in
muscular infundibulum and the pulmonary valve itself may cases of TOF-PA.3,13
then be patent (Figures 1A to C).3,7-9
Collaterals
Pulmonary Artery
In PA-VSD, the lungs are perfused by systemic to arterial
The pulmonary trunk is either a vestigial cord or a hypoplastic collaterals, which are essential for survival. The term collateral
funnel-shaped channel that widens as it approaches the artery refers only to the vessel connecting the aorta with a
bifurcation. The proximal pulmonary arteries are hypoplastic pulmonary arterial segment.14 The pulmonary circulation
and may be discontinuous.7 in PA-VSD is characterized by extreme heterogeneity and
When the pulmonary valve is imperforate, the pulmonary variability in terms of origin of the blood flow, the presence
trunk is present and patent to the level of the ventriculopulmonary or absence of the native pulmonary arteries (NPA), the
junction. In many other cases, the pulmonary trunk itself is presence or absence of MAPCA(s) and the distal distribution
atretic. In extreme cases, it is recognisable only as a fibrous of the pulmonary blood flow with frequent arborization
strand. When the right and left pulmonary arteries are present, abnormalities. The type of intracardiac malformation is not
usually they are confluent. The right and left pulmonary predictive of the pulmonary circulation.15,16
arteries can be nonconfluent, but one of them usually retains its A MAPCA is a large tortuous collateral artery, which almost
connection to the remnant of the pulmonary trunk.10,11 always arises from the anterior surface of the descending
aorta just beneath the carina or subclavian arteries, loops
CALIBER OF CENTRAL Pulmonary artery independent of the course of the bronchus to the lung and
connects with intrapulmonary arteries at the posterior aspect
The caliber of the central pulmonary artery12 is directly related of the hilum.12,15
to: The NPA may be severely hypoplastic, either confluent or
• Amount of blood flow nonconfluent or may be completely absent. They may derive their
• Connection of ductus or collaterals blood flow from either the ductus arteriosus, communicating
– Ductus/collaterals connect proximal to the central MAPCA(s) or both.17-20 Rabinovitch and associates21 have
pulmonary artery or lobar branches – pulmonary artery categorized systemic pulmonary collateral arteries into three
is mildly hypoplastic or normal. types (Figure 2), based on their site of origin as well as the way
– Multiple collaterals anastomose more distally at the they connect to the pulmonary circulation. These are direct
segmental or subsegmental levels – pulmonary arteries aortopulmonary collaterals, indirect aortopulmonary collaterals
are more likely to be hypoplastic. and true bronchial arteries (Table 1).21
566
Table 1
39
Characteristics of systemic collateral arteries21
Ductus
similar to a systemic arterial collateral with few differences
The pulmonary arteries are supplied primarily, if not (Table 2).14 This ductal structure is appropriate for 567
exclusively by a long, narrow, sigmoid shaped ductus intrauterine flow, which is directed from the aorta into the
arteriosus i.e. structurally a muscular systemic artery pulmonary artery. It is also termed ‘vertical ductus’ as it
http://vip.persianss.ir
8 i. Type A—NPAs are present. Pulmonary blood flow is
supplied by the patent ductus arteriosus (PDA). There are
no MAPCA(s).
Cyanotic Heart diseases
CLASSIFICATION
A B
Classification can be based on either pulmonary circulation or
on intracardiac anatomy.
http://vip.persianss.ir
8 pulmonary vascularity depend on the pulmonary blood flow. Abrupt change in the caliber of aorta or its branches gives
Children with balanced circulation show a normal sized an insight into the origin of the collateral arteries.
cardia with apparent normal pulmonary vascularity. Children Transthoracic echocardiography can serve as a sensi
Cyanotic Heart diseases
with excessive pulmonary blood flow have cardiomegaly tive and specific diagnostic test for the detection of aorto
and excessive pulmonary vascularity. Cyanosed children pulmonary collaterals in infants with TOF/PA. The extent
usually have a normal sized cardiac silhouette with patchy of aortopulmonary collaterals is inversely related to the
lung markings depending on collateral supply. Some areas diameters of the central pulmonary arteries. The presence
of lung might be underperfused while some might be
overperfused.3,8,9,13 Rarely, pulmonary atresia and a large
vertical patent ductus arteriosus which, while acting as the
only source of pulmonary blood supply, can compress the left
main bronchus, causing hyperinflation of the left lung.25
Echocardiography
Detailed echocardiographic evaluation is necessary for
establishment of diagnosis and to plan further management.
In nutshell, echocardiography is helpful:
• To see whether pulmonary arteries are confluent
• To see pulmonary artery caliber
• To ascertain presence of collaterals and delineation of their
origins
• To see unusual origins of collaterals
• To plan for a roadmap for catheterization and transcatheter
palliation (PDA stenting)
• In post procedural assessment
Parasternal long-axis view as well as subcostal views
very well show the dilated aorta over-riding the crest of the
ventricular septum (Figure 5). The ventricular outflow tract
can be profiled in paraternal short axis views as well as in Figure 6: Subcostal view showing a blindly ending muscular
subcostal views to see a blindly ending muscular infundibulum infundibulum. IVS = Interventricular septum; LV = Left ventricle; RV
= Right ventricle.
(Figure 6). High parasternal and suprasternal views best depict
the ductal and branch pulmonary artery anatomy (Figures 7
to 9). Color flow Doppler helps in diagnosing imperforate
pulmonary valve as well as in assessing the presence of
collateral arteries.26
570
Figure 5: Subcostal view showing a large VSD and over-riding Figure 7: Suprasternal long-axis view showing large vertical ductus
aorta. IVS = Interventricular septum; LV = Left ventricle; RV = Right with distal constriction arising from undersurface of aortic arch and
ventricle; VSD = Ventricular septal defect. supplying pulmonary arteries arteries (PA).
Computerized Tomography 39
Computerized tomography (CT) helps in comprehensive
http://vip.persianss.ir
8
Cyanotic Heart diseases
Figure 11: Sagittal CT section showing large ductus supplying ANATOMICAL DELINEATION
pulmonary arteries (PA)
• Detailed analysis of pulmonary supply
– Assess size of NPAs and the extent of its arborization
into lung parenchyma
– Type of systemic-pulmonary collateral and its
significance in terms of segmental supply by selective
canulation
– Identify degree of intercommunication between various
vascular pathways by selective balloon occlusion34
(Figure 18).
METHODS
1. Retrograde arterial approach is easy. A descending
aortogram in anteroposterior projection gives a non
selective detailing of number and size of collaterals. The
collaterals can then be selectively catheterized and injected
to get an idea of segmental supply.
2. Pulmonary venous wedge angiography is helpful in
delineating true pulmonary artery in levophase especially
if the NPAs are inaccessible (Figure 19).
Figure 12: VR CT angiogram in a 15 months old child with PA/VSD 3. Photographic subtraction of appropriately chosen large film
showing nonconfluent pulmonary arteries arising from the aorta. angiograms can serve to delineate sources of pulmonary
Image Courtsey: Dr Madhav Hegde
blood flow.35,36
• Determine source (s) of pulmonary blood flow Cardiac Magnetic Resonance Imaging
• Delineate size and distribution of true pulmonary arteries
(Figure 15) Gadolinium enhanced three-dimensional magnetic resonance
• Ascertain extent of collateral blood supply to lungs (Figures angiography (Gd-MRA) has been shown to noninvasively
16 and 17) and accurately evaluate various lesions of the vascular
• True pulmonary artery pressure and resistance. system. Magnetic resonance angiography can delineate all
572
39
C D
Figures 14A to D: A. angiogram through the vertical duct shows confluent pulmonary arteries with ostial stenosis of left pulmonary artery; B.
Aortic arch angiogram shows multiple aortopulmonary collateral arteries (MAPCAs) supplying both lungs and with non-confluent pulmonary
arteries; C. Descending aorta angiogram shows confluent pulmonary arteries with dual supply to the left lung; D. Selective angiogram shows
Blalock-Taussig (BT) shunt opacifying the confluent pulmonary arteries. AO = Aorta; PA = Pulmonary artery. Image courtsey: Dr IB Vijayalakshmi
sources of pulmonary blood supply in cyanotic congenital estimate the pulmonary to systemic blood flow ratio (QP/QS
heart disease with pulmonary stenosis and/or atresia as well = QPV/(QAO-QPV)) and the amount of blood flow to each
as provide accurate assessment of pulmonary artery size for lung. The contribution of a PDA or large aortopulmonary
planning corrective surgery.37 Magnetic resonance imaging collateral to the pulmonary blood supply may be assessed, but
in pulmonary atresia provides an alternative non-invasive investigation of all aortopulmonary collaterals would be tedious
method of obtaining much of the anatomical information and imprecise if they are small. With optimisation of current
required to plan surgical treatment and should reduce the need CMR techniques for imaging neonates, it should be possible to
for invasive angiography in these patients, besides depiction measure flow volumes with sufficient accuracy in vessels larger
of the pulmonary arterial anatomy.38 than 2 mm diameter. Contrast-enhanced magnetic resonance
Cardiovascular magnetic resonance (CMR) may also angiography (CE-MRA) is a useful diagnostic tool in clinical
provide hemodynamic information by obtaining additional routine for the preoperative evaluation of the morphology of
velocity-encoded phase-contrast cine sequences. In patients the pulmonary arteries and pulmonary circulation in neonates
with pulmonary atresia, flow volume measurements in the with pulmonary atresia. In most cases additional diagnostic
ascending aorta and in each pulmonary vein can be used to cardiac catheterization can be avoided.39 573
http://vip.persianss.ir
8
Cyanotic Heart diseases
Figure 15: Pulmonary artery angiography of native pulmonary arteries Figure 16: Angiography through injection in left subclavian artery
supplied by a vertical ductus. LPA = Left pulmonary artery; RPA = showing an indirect aortic collateral
Right pulmonary artery.
Figure 17: Aortic root angiogram in left anterior oblique projection Figure 18: Balloon occlusion to facilitate delineation of coronary to
showing pulmonary artery originating from coronary artery. LMCA = pulmonary artery supply. LMCA = Left main coronary artery. MPA =
Left main coronary artery; MPA = Main pulmonary artery. Main pulmonary artery.
Pulmonary atresia-ventricular septal defect can be diagnosed Pulmonary atresia-ventricular septal defect remains one of
by fetal echocardiography with a high degree of accuracy. the most challenging groups to manage. The quest for optimal
574 However, it can be difficult to determine the morphology management of this complex anomaly is, as yet, an ongoing
of the central pulmonary arteries and to locate the source of process. The treatment of PA-VSD has been largely determined
pulmonary blood supply.40 by the morphology of the pulmonary circulation (Figure 20).
Systemic-pulmonary Shunts 39
Neonatal shunting regimen (modified BT shunt), without
Unifocalization
The unifocalization procedures are designed to improve
the arborization pattern of the central pulmonary arteries.
Figure 20: Plan for management of PA-VSD. Type A- Restoration of Systemic collateral arteries are essentially arterial conduits
neonatal pulmonary blood flow by systemic to pulmonary (S-P) shunt connecting the systemic circulation to the true pulmonary
or patent ductus arteriosus (PDA) stenting followed by intracardiac
repair (ICR). They can go for neonatal ICR, if feasible. Type B and arterial segments. This allows their use for the purposes
C- Treatment strategy is individualized and involves unifocalization of increasing pulmonary arterial runoff from the central
procedures, establishing ventricle-pulmonary artery continuity and pulmonary arteries. Systemic collateral arteries that connect
closure of ventricular septal defect. Cases where biventricular repair freely with the central pulmonary arteries (communicating)
is not feasible, one can follow the usual strategy for a single ventricle
pathway in suitable patients can be interrupted, whereas those that do not have
unrestricted connections with the central pulmonary arteries
(non-communicating) must be detached from their origin,
Pulmonary Artery Rehabilitation mobilized and connected surgically to the central pulmonary
arteries or their branches.
A strategy aiming at the development of native pulmonary arteries Pulmonary reperfusion injury is common after the
and a biventricular repair is feasible in most cases and should unifocalization procedure. Severity of MAPCA stenosis and
be done early in life, since long term future of true pulmonary bilateral unifocalization are associated with the development 575
arteries may possibly be better than flow through the collaterals.41 of reperfusion injury.42
http://vip.persianss.ir
8 via anastomosis of collaterals to other collaterals and to the
native pulmonary arteries.61
Cyanotic Heart diseases
Complete Repair
It involves establishing continuity between ventricle and
pulmonary arterial confluence along with closure of VSD.
If main pulmonary artery is present, repair can usually be
performed by opening the atretic segment and performing a
reconstruction with a transannular patch, avoiding a conduit,
not unlike a standard tetralogy repair. Even in the presence
of discontinuity between the right and left pulmonary artery,
establishment of a pulmonary artery confluence by direct
anastomosis can be achieved. In recent years some groups,
have increasingly favored a primary neonatal intracardiac
Figure 21: Aortic injection showing coronary stent in position repair.
across the vertical ductus into pulmonary artery
577
http://vip.persianss.ir
8 7. Edwards JE Mchoon DC. McGoon. Absence of anatomic
origin from heart of pulmonary arterial supply. Circulation.
25. Markowitz RI, Fahey JY, Hallen brand We Am J Roentoenol,
et al. Bronchial compression by a patent ductus arteriosus
1973;47:393-98. associated with pulmonary atresia. AJR. 1985;144:535-40.
Cyanotic Heart diseases
8. Freedom RM, Yoo S, Makailian H, William W (Eds). The 26. Snider AR, Serwer GA, Ritter SB. Echocardiography in
natural and modified history of Congenital heart disease. Ist pediatric Heart Disease. 2nd edition. Mosby.
edition. Wiley-Blackwell. 27. Mackie AS, Gauvreau K, Perry SB, et al. Echocardiographic
9. Anderson RH, Baker EJ. In: Anderson RH, Baker EJ, Penny predictors of aortopulmonary collaterals in infants with
DJ, Redington AN, Rigby ML, Wernovsky G (Eds). Pediatric tetralogy of Fallot and pulmonary atresia. J Am Coll Cardiol.
Cardiology, 3rd edition. Churchill Livingstone Elsevier. pp. 2003;41:852-7.
775-793. 28. Marino, Pasquini L, Guccione P, et al. Pulmonary atresia with
10. Thiene G, Bartolotti U, Gallucci V, et al. Pulmonary atresia ventricular septal defect. Selection of patients for systemic-
with ventricular septal defect. Further anatomical observations. to-pulmonary artery shunt based on echocardiography. Chest.
Br Heart J. 1977;39:1223-33. 1991;99:158-61.
11. Freedom RM, Benson LN, Smallhorn JF (Eds). Neonatal Heart 29. Rajeshkannan R, Moorthy S, Srukumar KP, et al. Role of 64-
Disease, 1st edition. Springer Verlag. MDCT in evaluation of pulmonary atresia with ventricular
12. Haworth SG, Macartney FJ. Growth and development of septal defect. AJR 2010;194:110-18.
pulmonary circulation in pulmonary atresia with ventricular 30. Yu CH, Chen MR. Clinical investigation of systemic-
septal defect and major aortopulmonary collateral arteries. Br pulmonary collateral arteries. Pediatr Cordiol. 2008;29:334-38.
Heart J. 1980;44;14-24. 31. Prieto Lr. Management of tetralogy of Fallot with pulmonary
13. Perloff JK. Ventricular septal defect with pulmonary stenosis. atresia. Images Paediatr Cardiol. 2005;24:24-42.
Clinical Recognition of Congenital Heart disease. 5th edition. 32. Moll JN, Santos MA, Drumond C, et al. Improved visualization
WB Saunders. pp. 348-82. of aortopulmonary collateral arteries by abdominal aortic
14. Haworth SG. Collateral arteries in pulmonary atresia with compression during angiography. Circulation. 1982;65:
ventricular septal defect. A precarious blood supply. Br Heart J 953-55.
1980;44:5-13. 33. Feltes TF, Bacha E, Beckman RH, et al. Indications for cardiac
15. Jefferson K, Rees S, Somerville J. Systemic arterial supply to catheterization and intervention in pediatric cardiac disease:
the lungs in pulmonary atresia and its relation to pulmonary a scienfic statement from the American heart Association.
artery development. Br Heart J. 1972;34:418-27. Circulation. 2011;123:2607-52.
16. Macartney FJ, Scott O. Deverall PB. Haemodynamic and 34. Lim JSL, Desai T, Stumper O. Dual-catheter balloon occlusion
anatomical characteristics of pulmonary blood supply in aortography in pulmonary atresia with ventricular septal
pulmonary atresia with ventricular septal defect - including a defect and major aorto-pulmonary collaterals. Pediatr Cardiol.
case of persistent fifth aortic arch. Br Heart J. 1974;36:1049- 2004;25:500-02.
60. 35. Fsulton RE, Davis GD. Congenital pulmonary atresia:
17. Amin Z, McElhinney DB, Reddy VM, et al. Coronary to photographic subtraction as an aid in recognizing hypoplastic
pulmonary artery collaterals in patients with pulmonary atresia pulmonary arteries. Am J Roentgenol. 1978;131:1003-07.
and ventricular septal defect. Ann Thorac Surg. 2000;70:119- 36. Elliott LP, Bargeron LM Jr, Brean PR, et al. Axial
23. cineangiography in congenital heart disease. Section II. Special
18. Nørgaard MA, Alphonso N, Cochrane AD, et al. Major aorto- lesions. Circulation. 1977;56(6):1048-93.
pulmonary collateral arteries of patients with pulmonary atresia 37. Srinivas B, Patnaik AN, Rao DS. Gadolinium-enhanced three-
and ventricular septal defect are dilated bronchial arteries. Eur dimensional magnetic resonance angiographic assessment of
J Cardiothorac Surg. 2006;29:653-58. the pulmonary artery anatomy in cyanotic congenital heart
19. Faller K, Haworth SG, Taylor JF, et al. Duplicate sources of disease with pulmonary stenosis or atresia: comparison with
pulmonary blood supply in pulmonary atresia with ventricular cineangiography. Pediatr Cardiol. 2011;32(6):737-42.
septal defect. Heart. 1981;46:263-68. 38. Rees RSO, Somerville J, Underwood SR, et al. Magnetic
20. Ramsay JM, Macartney FJ, Haworth SG. Tetralogy of resonance imaging of the pulmonary arteries and their
Fallot with major aortopulmonary collateral arteries. Heart. systemic connections in pulmonary atresia: comparison with
1985;53:167-72. angiographic and surgical findings. Br Heart J. 1987;58:621-26.
21. Rabinovitch M, Herrera-deLeon V, Costaneda AR, et al. 39. Kawel N, Valsangiocomo-Buechel E, Hoop R, et al.
Growth and Development of the Pulmonary Vascular Bed in Preoperative evaluation of pulmonary artery morphology and
Patients with Tetralogy of Fallot with or Without Pulmonary pulmonary circulation in neonates with pulmonary atresia-
Atresia. Circulation. 1981;64:1234-49. usefulness of MR angiography in clinical routine. J cardiovase
22. Kirklin JW, Barrat-Boyes BG, Ventricular Septal Defect magn reson. 2010;12:52.
and Pulmonary stenosis and Atresia. 2nd edition. Churchill 40. Vessel S, Roltings S, Jones A, et al. Prenatally diagnosed
Livingstone: pp.816-1012. pulmonary atresia with ventricular septal defect: echocardio
23. Jonas RA. Comprehensive Surgical Management of Congenital graphy, genetics, associated anomalies and outcome. Heart.
Heart Disease. 1st edition. Hodder Arnold. 2006;92:1501-05.
24. Haworth SG, Rees PG, Taylor JFN, Macartney FJ, et al. 41. Metrasa D, Chetailleb P, Kreitmanna B, et al. Pulmonary
Pulmonary atresia with ventricular septal defect and major atresia with ventricular septal defect, extremely hypoplastic
aortopulmonary collateral arteries Effect of systemic pulmonary arteries, major aortopulmonary collaterals. Eur J
578 pulmonary anastomosis. Br Heart J. 1981;45:133-41. cardiothorac Surg. 2001;20:590-96.
42. Liava'a M, Thomson LD, et al. Pulmonary atresia, ventricular ventricular septal defect be closed? J Thorac Cardiovasc Surg. 39
septal defect, and major aortopulmonary collaterals: neonatal 1997;113:858-68.
pulmonary artery rehabilitation without unifocalization. Ann 58. Murthy K, Reddy KP, Nagarajan R, et al. Management of
http://vip.persianss.ir
C hapter
Membranous Atresia, Tripartite RV, Mild RV Hypoplasia At the other end of this continuum is the RV which is severely
hypoplastic on account of complete or near obliteration of the
At one end of this spectrum are hearts where the RV is infundibulum by muscle, i.e. 'muscular' atresia.9,17,21,22 Often,
near normal in size and morphology. The inlet, trabecular what appears to be complete obliteration of the infundibulum,
and infundibular components are well developed and the upon probing with a catheter at angiography may reveal a tiny
pathologic abnormality is a thin membranous imperforate slit reaching up to the valve annulus (Figure 2). However it is
valve (Figures 1A and B). This can perhaps be considered doubtful if this can be refashioned into a functioning RVOT.
A B C
Figures 1A to C: Membranous atresia with well-developed right ventricle (RV): A. RV angiography in anteroposterior projection showing inlet,
apical trabecular and infundibular components of the RV. The infundibulum (INF) is widely patent, but ends blindly at the valve. A dilated right
ventricle is opacified by moderate tricuspid regurgitation; B. Simultaneous injection in the infundibulum and aorta opposite the patent ductus
arteriosus (PDA) in lateral projection showing very thin, membraneous valve. Arrow shows well-developed main pulmonary artery sinuses 581
'cupping' over the membranous valve and annulus; C. Fixed stenosis due to thick muscle bundles in the subvalvar area (arrow), resulting in
failure of RV decompression. The atretic valve has been opened with radiofrequency valvotomy and balloon dilatation
http://vip.persianss.ir
8
Cyanotic Heart diseases
A B A B
Figures 2A and B: Muscular atresia with generally hypoplastic right Figures 3A and B: Membranous atresia with moderate right ventricle
ventricle (RV): A. RV angiogram in anteroposterior (AP) projection (RV) hypoplasia (intermediate): A. RV angiogram in anteroposterior
showing mainly an inlet component of the RV. The outlet component projection showing an overall small RV, but three components of the RV
is merely a slit that extends towards where the valve annulus should are present. The apical trabecular component is the least developed.
normally be (thin arrow). An RV-coronary connection with stenosis is Numerous minor RV-coronaries connections are present; B. Bipartite
seen (broken arrow); B. RV angiogram in AP projection of another RV- the inlet and outlet components are well-developed, but the apical
patient with muscular atresia with severely hypoplastic RV. 2 large trabecular component is virtually obliterated by muscles except for
RV-coronary connections are seen (arrows) some intertrabecular recesses. There is mild tricuspid regurgitation
The trabecular component, except for slits of inter-trabecular Minor connections < 2 mm are not uncommon, but ectatic
spaces is also virtually obliterated by muscle, leaving a severely connections may also be present. In our series of 143 patients,
attenuated inlet part of the RV guarded by a TV, which has a 25.9 percent were categorized as those with 'intermediate'
hypoplastic annulus. These are hearts whose RV is unlikely subgroup or having bipartite RV.27 With adequate opening
to be able to support the pulmonary circulation independently, of the atretic valve, the well-developed infundibulum allows
hence destined for single ventricle management pathway. This unobstructed flow into the pulmonary arteries.
subgroup made up 7.7 percent of the UK and Eire collaborative
study3 whereas it appeared to make up a far higher proportion Thinned and Dilated RV, Ebstein’s Anomaly or
in one hospital based study.23 Dysplastic Tricuspid Valve
There is a strong correlation between muscular atresia of
the infundibulum and severe RV hypoplasia with the presence Somewhat outside this continuum of RV morphology from
of major RV—coronary arterial connections. Some of these near normal RV to the severely hypoplastic, unipartite RV
are associated with major obstructions and interruptions of the are the rare patients with PAIVS in association with severe
proximal coronary arteries, making the coronary circulation Ebstein’s anomaly or dysplasia of the TV. The RA and
‘RV dependent’ (Figures 2A and B).24-26 atrialized RV are markedly dilated giving rise to a 'wall to
wall' heart. The remaining part of RV and infundibulum
Moderate RV Hypoplasia, Bipartite RV, Membranous are also markedly thinned and dilated, ending blindly in
Atresia (Intermediate) an atretic pulmonary valve with a small annulus. This may
account for up to one-sixth of patients with PAIVS.11 In the
Between the two ends of the continuum are gradations of UK and Eire collaborative study this made up 5.4 percent.3
RV cavitary hypoplasia. In some of these patients, the three RV-coronary arterial connections are virtually unknown in
components of the RV are moderately hypoplastic due this subgroup.
to muscular overgrowth significantly reducing the apical
trabecular component and the infundibulum. However, we also Right Atrium, Right Ventricle and Tricuspid Valve
observe that in others only the apical trabecular component is
virtually obliterated save for slits of inter-trabecular spaces The tricuspid valve too often exhibits a range of abnormalities
whereas the inlet and the infundibulum are reasonably well from the severely stenotic valve with very small annulus
developed, i.e. a ‘bipartite’ RV. The infundibulum ends blindly to the severely dysplastic valve or frank Ebstein’s anomaly
with membranous atresia (Figures 3A and B). We term this causing severe regurgitation.5 Even when the valve apparatus
group of patients as ‘intermediate’ RV. The TV Z score may appears normal, a mild degree of TR is often seen due to the
not be as satisfactory as those with favourable anatomy, giving high RV pressure.
values between –2.0 to –5.0 and, so are the other values of RV The RA is often mildly dilated in the presence of a
dimensions such as inlet length and TV/mitral valve annulus competent TV due to poor RV compliance. When there is
ratio. The occurrence of RV-coronary arterial connections severe TR due to dysplastic valve or Ebstein’s anomaly, the
582 in this subgroup also lies somewhat in between the two. RA will be markedly dilated.
Patent Ductus Arteriosus, Pulmonary Arteries Coronaries Arteries 40
and Pulmonary Valve
A peculiar feature of PAIVS is its association with
http://vip.persianss.ir
8
Cyanotic Heart diseases
A B C
Figures 5A to C: Right ventricle (RV)-coronary connections: A. A major communication to the right coronary artery (RCA). A mild narrowing is
noted (arrow), but the entire RCA and aortic root is opacified; B. Communication to the left coronary artery. A severe stenosis is seen (broken
arrow) distal to the major branches. It is assumed that the left coronary is not RV dependent as the major branches are perfused antegradely
from the aorta; C. A major communication to the RCA is seen (thick arrow) with no obvious stenosis and numerous minor communications.
Bipartite RV with a well-developed infundibulum, but the apical trabecular component is virtually obliterated
the presentation of infants with this disease correlates with Chest X-ray
constriction and closure of the ductus arteriosus, which
generally takes place in the neonatal period. Cyanosis is Features that may suggest the diagnosis of PAIVS are right
the most common presentation. Occasionally, especially in atrial enlargement in cases where there is significant TR,
communities with limited access to medical care, these infants and an oligaemic lung fields. This however may be difficult
may present in a critical state with low output and acidosis to distinguish from normal in the neonate. The appearance
consequent to severe hypoxemia. of wall-to-wall heart, a feature of severe Ebstein’s anomaly,
As fetal cardiac service is increasingly becoming a should also raise the possibility of coexisting true, anatomic
norm, fetal diagnosis of PAIVS allows early transfer to pulmonary atresia (Figure 6).
specialized cardiology unit, minimizing the problems related
to late diagnosis.14 Management plan can also be formulated
antenatally with the interventional and surgical team. Infants
with PAIVS in association with severe Ebstein’s anomaly and
wall-to-wall heart may present with severe profound hypoxemia
that respond poorly to prostaglandin as the compressed lungs
may be underdeveloped and hypoplastic.35-37
As with many other cyanotic heart disease presenting in the
neonatal period, physical signs are generally inconspicuous
apart from cyanosis. The murmur from the ductus arteriosus
may not be readily audible in all patients. The presence of
significant TR may provide additional signs such as an
enlarged liver and a high pitched pansystolic murmur over the
lower left sternal edge.
INVESTIGATIONS
Electrocardiogram
The Electrocardiogram (ECG) in PAIVS characteristically
displays a QRS axis that is less rightward than normal, i.e.
between 30° to 90°, and ‘adult’ precordial pattern rather
Figure 6: Postero-anterior chest radiograph showing a 'wall to wall'
than the usual right ventricular hypertrophy.5 The tall peaked heart in a neonate with PAIVS in association with severe Ebstein’s
584 P-waves of right atrial enlargement may be present. malformation of the tricuspid valve
Imaging and Hemodynamics—Echocardiography, hypoplastic, with only a very small inlet guarded by a small 40
Cardiac Catheterization and Angiography TV. The apical trabecular component is obliterated as is the
outlet, i.e. muscular atresia.
http://vip.persianss.ir
8 Cardiac Catheterization and Angiography infants or those small for gestational age, prolonged PGE1
infusion may be necessary before it is considered safe or
Although echocardiography can readily confirm the diagnosis feasible for surgical or catheter intervention. In our own
Cyanotic Heart diseases
and provide anatomic details that would be important for experience, it is best for the infant to achieve a weight of
management strategy, PAIVS is one condition where cardiac 3.0 kg before any form of intervention is considered.
catheterization and angiography remains an essential part Today, better understanding of the wide morphologic
of the initial evaluation.1 This is particularly so for centers variation of the disease, as well as advances in surgical and
where catheter based therapy plays a prominent role in the interventional techniques have led to better early survival and
management of this disease. at least medium term outcome of this disease.8,9,12,17,23,43-48
Firstly, even if the size and morphology of the RV can be In patients with the most favorable anatomy with
obtained by echocardiography, detailed characterization of the membranous atresia and all three parts of the RV being well
RV such as the degree of obliteration of the apical trabecular developed, RV decompression in the neonatal period with
zone and the RVOT may be difficult. Intertrabecular spaces either surgical valvotomy or transcatheter method would often
in this region may not be obvious. In the RVOT, presence of be the only procedure required, and thereafter it is reasonable
muscle bundles that reduce the infundibular cavity or cause to expect normal two-ventricle circulation with no further
fixed subvalvar obstruction, the size of the pulmonary valve procedures required at least until early adult life. However this
annulus, thickness of the atretic valve plate and the dimension may apply to only about half of PAIVS patients.
of pulmonary artery root can only be detailed accurately by In the remainder, multiple interventions, either surgical or
angiography. In hearts with diminutive unipartite RV, a tiny transcatheter, will be required at least in the first few years
slit-like infundibulum is not uncommonly present when RV of life. Hence, a good teamwork between the interventional
angiography is performed (see Figure 2A). This impacts on cardiologist, cardiac surgeons and the rest of the care givers
one’s decision whether transcatheter perforation of the atretic involved is essential in the management of these patients.
valve and RV decompression by balloon dilatation would be From the outset the parents should be counselled regarding
the appropriate management. the nature of their infant’s specific morphologic details, the
Another reason for angiography remaining an essential likely clinical course and the long-term treatment plan and
imaging technique is for the detailed evaluation of ventriculo- goals, which may require significant revisions along the way
coronary connections (see Figure 5).17,35 Whilst large ectatic according to the outcome of preceeding treatments.
connections can be seen by echocardiography without The desired goal is to achieve eventual two-ventricle
difficulty, the dimensions, course and more importantly the circulation with all intracardiac and extracardiac shunts
presence or otherwise of stenoses, interruptions and absent (PFO/ASD and Blalock Taussig shunt/PDA stent) closed,
aortic-coronary connection of this abnormality is beyond the obstruction to RV outflow virtually abolished and significant
capability of this otherwise excellent non-invasive imaging tricuspid valve regurgitation corrected. However this goal is
technique. Minor connections may not be detected by perhaps realistically achievable in only 50 to 60 percent of
echocardiography. Similarly echocardiography is limited in patients. Some patients from the outset appear destined for
its capability for full characterization of the PDA morphology, the single ventricle track and in between are those in whom it
an important consideration when PDA stenting is planned as is reasonable to set the objective of two ventricle-circulation
alternative to conventional systemic-pulmonary shunt.41,42 at the first assessment but eventually this may need to be
Additionally, cardiac catheterization provides important downgraded to what is termed '1½ ventricle circulation'
hemodynamic data such as RV systolic pressure, central when the RV does not grow sufficiently after successful RV
venous pressure (CVP), aortic pressure, LV end-diastolic decompression. Cardiac transplantation may be advocated in
pressure and systemic oxygen saturation. the rare cases of severe RV hypoplasia with major ectatic RV-
coronary connections and RVDCC and in those with extreme
MANAGEMENT Ebstein’s anomaly with wall-to-wall heart, it may be wise to
offer compassionate care.
Pulmonary artesia with intact ventricular septum (PAIVS) Our management algorithm is based on morphologic
being a duct-dependent lesion, survival beyond the neonatal evaluation by echocardiography and RV angiography. As
period or early infancy is not possible without intervention described in the foregoing sections there is a spectrum of
except in the rare cases where aortopulmonary collaterals RV size and morphology. For making clinical decisions and
provide a stable source of pulmonary blood flow. Intravenous long term plan and counseling, it is practical to categorize
PGE1 infusion to maintain ductal patency is an important first patients as having good RV size and morphology, severe RV
line treatment. Acidosis, hypothermia and poor peripheral hypoplasia with muscular atresia and in between these two
perfusion should be corrected when present. For preterm extremes, those with 'intermediate' RV.10
586
Good Right Ventricular Size and Morphology 40
In this subgroup all three parts of the RV are well-developed,
http://vip.persianss.ir
8 and only a diminutive inlet is present guarded by a very small problems with transplantation, this is hardly considered
tricuspid valve, RV decompression is not likely to be feasible today.23,64,65
at the outset. Repair towards single-ventricle circulation is the
Cyanotic Heart diseases
D E
Figures 9A to E: PAIVS with moderate right ventricle (RV) hypoplasia. Radiofrequency (RF) valvotomy, balloon dilatation and concomitant
elective patent ductus arteriosus (PDA) stenting. A. RV handshot showing bipartite RV with fairly well-developed infundibulum with membranous
atresia (thick arrow) and inlet component (thin arrow). Muscle bound apical trabecular component of RV (area within dotted lines). Except for
the intertrabecular recesses, the cavity is virtually obliterated. Membranous atresia seen. RV: AO pressures = 153:73 mm Hg; B. RV angiogram
following RF valvotomy and balloon dilatation. Transient reactive spasm reduces RV outflow tract cavity; C. PDA crossed with a balloon mounted
coronary wire retrogradely; D. Stent expanded and covering the full length of the PDA; E. RV angiogram 4 years post RF valvotomy and PDA
stenting showing a well-developed RV, unobstructed pulmonary blood flow, no branch pulmonary artery stenosis and regression of muscular
overgrowth resulting in a well-formed cavity of apical component of RV. Excellent overall growth of RV; 'tripartite' end state. The PDA stent is
hardly visible
Glenn shunt is created, PDA stent divided and PFO Instead of conventional surgery with the construction of BT
closed.12,66-68 shunt and repair of the TV, RVOT reconstruction + reduction
Additional problems such as subvalvar stenosis and TR are of the grossly dilated right chambers, the technique advocated
tackled preferably at the same time. Only short and medium by Starnes has shown some commendable, if mixed results.70
term data is available, but this approach appears a reasonable This involves converting the TR to atresia and the construction
strategy for this group of patients with 'intermediate' RV.27 of BT shunt, followed later by single-ventricle palliation.
Starnes’ original patients were those with severe Ebstein’s
Thinned and Dilated Right Ventricular, Ebstein’s with functional pulmonary atresia, but fundamentally the
Anomaly, Severe Tricuspid Regurgitation technique can be equally applied to those with anatomic
atresia of the pulmonary valve. Nevertheless this subgroup of
The final subgroup of PAIVS patients are those associated patients, whose grossly dilated and thinned out RV falls outside
with severe Ebstein’s malformation or dysplasia of the TV, the continuum of mild to very severe hypoplasia, continues
leading to very severe TR, thinned out RV and grossly dilated to have the poorest prognosis when major improvement in
right heart chambers, i.e. the 'wall-to-wall heart'. While early medium term survival has been achieved for the others.
and medium term survival of those with diminutive RV and One of the attractive, potential merits of fetal intervention
major RV-coronary connections have improved significantly is alteration of natural course of disease. If fetuses who can
with single ventricle palliation, the prognosis for those be predicted to develop grossly dilated right heart and severe 589
severely dilated thinned out RV remains very poor.11,43,69 tricuspid regurgitation can be identified, perhaps this is one
http://vip.persianss.ir
8 indication for such a procedure.71,72 However, apart from essentially a near normal RV with membranous atresia of
accurate diagnosis and 'patient' (fetus) selection, there are the pulmonary valve to a complex malformation where the
major issues of competence and training of the fetal cardiology RV is almost obliterated by muscles except for a diminutive
Cyanotic Heart diseases
team, service organization and of ethics that make this still an inlet cavity and frequently associated with major RV-coronary
experimental procedure. connections. Between the extremes are hearts with varying
degrees of RV cavitary hypoplasia particularly involving the
PROGNOSIS AND LONG-TERM SURVIVORS apical and infundibular parts, abnormalities of the tricuspid
OF pulmonary atresia with INTACT valve and less severe forms RV-coronary connections.
ventricular septum Echocardiography has played a major role in the
understanding PAIVS morphology and morphometry of
Pulmonary atresia with intact ventricular septum remains the right heart structures such as the size of the TV and RV
among lesions that have higher risks for morbidity and lower 1 inlet length allows a semi-quantitative assessment of the
and 5 year survival. Low birth weight, unipartite RV, significant severity RV underdevelopment. However PAIVS is one
RV dilatation/Ebstein’s anomaly and greater severity of condition where the invasive cardiac catheterization remains
coronary arterial abnormalities and earlier era of surgery an essential imaging tool especially in the evaluation of RV-
are the commonly cited independent risk factors.12,43,69,73 coronary connections. This is particularly so in the current
However, with better understanding of the remarkably varied era of interventional cardiology where pulmonary valvotomy
anatomy of PAIVS and management strategies based on RV with balloon dilation, and to certain extent PDA stenting are
morphology, the outlook for these patients has continued to the preferred initial management in many centers.
improve. Advances in surgical techniques, ICU care and the A better understanding of the RV morphology allows
less invasive transcatheter techniques have also in a large formulation of management strategies that will result in
measure contributed to the current medium term results. It the best outcome for the patients. Although the 2-ventricle
remains to be seen, however, what happens to these patients circulation is desirable, this is only achievable in only about
in the long term. 60% of patients. For patients with the most severe form of
Present adult survivors of PAIVS belong to an earlier the disease, clearly the single-ventricle track is the only
surgical era and data is understandably scant. In a 12 year viable option, with the attendant late problems following the
study of 20 adult survivors of PAIVS, John et al reported five Fontan operation. Premature atherosclerosis due to coronary
deaths and all patients required reinterventions. 74 12 patients arteries perfused by hypertensive RV in those with RV-
had single ventricle anatomy and received Fontan operation or coronary connections is an added facet of late survival. The
palliative shunts and the remainder had 2 ventricle repair. The 1½ ventricle is an attractive option for those with moderate
highest number of reinterventions were in the biventricle repair RV hypoplasia where the bidirectional Glenn shunt partially
group, consisting of multiple pulmonary and TV replacements off loads the RV while maintaining pulsatile flow into the
and repairs, RV-PA conduit replacement, RVOT reconstruction, pulmonary circulation.
treatment of shunt-related RPA stenosis and mitral valve repair The outlook for many patients with PAIVS is better today
or replacement. In the single ventricle patients reoperation than it was 2 to 3 decades ago. However, for many who
were Fontan revision and conversion, fenestration and shunt survive into adult life with 2-ventricle circulation, progressive
revision or creation of an additional systemic-pulmonary shunt. tricuspid regurgitation and pulmonary regurgitation are likely
Although these patients were operated in an earlier era, to lead to re-interventions after many years of reasonably
the study highlights the multiple reinterventions that many normal survival. Transcatheter valve therapies are likely to
patients from the current era will likely need to undergo in change how this will be managed in the near future.
adult life due to the associated pathologies involving the The coming decades would be interesting to watch as
TV and pulmonary regurgitation that commonly results the cohort of patients from the current era reach adulthood,
following transcatheter or surgical valvotomy. However, especially those with 1½ and single ventricle circulation.
in the setting of two ventricle circulation, it is gratifying
to learn that late pulmonary valve replacement for severe It is not always in a physician's power to cure the sick; at
pulmonary regurgitation can be performed in PAIVS patients times the disease is stronger than trained art.
with excellent results, although results of TV repair suggest —Ovid
a need for further refinement of current surgical technique.75
REFERENCEs
Conclusion
1. Freedom RM, Nykanen DG. Pulmonary atresia and intact
In the last 2 decades there has been a tremendous improvement ventricular septum. In: Allen HD, Clark EB, Gutgesell HP,
in the understanding of the morphology of PAIVS, one that Driscoll DJ (Eds). Moss and Adams heart disease in infant,
590 is characterized by a remarkable diversity ranging from children and adolescents: including the fetus and young adult,
New York: Lippincott Williams and Wilkins; 2000. p. 845.
2. Perry LW, Neill CA, Ferencz C, Infants with congenital heart
disease: the cases. In: Ferencz C, Rubin JD, Loffredo CA,
20. Alwi M, Geetha K, Bilkis AA, et al. Pulmonary atresia with
intact ventricular septum percutaneous radiofrequency-assisted
40
Magee CA (Eds). Epidemiology of congenital heart disease. valvotomy and balloon dilation versus surgical valvotomy and
http://vip.persianss.ir
8 37. Lang D, Oberhoffer R, Cook A, et al. Pathologic spectrum of
malformations of the tricuspid valve in prenatal and neonatal
54. Kouchoukos NT, Blackstone EH, Doty DB, Hanley FL, Karp
RB (Eds). Cardiac surgery: morphology, diagnostic criteria,
life. J Am Coll Cardiol. 1991;17:1161-67. natural history, techniques, results and indication. 3rd Edition.
Cyanotic Heart diseases
38. Leung M, Mok CK, Hui PW. Echocardiographic assessment of Philadelphia: Elsevier; 2003. pp. 1095-112.
neonates with pulmonary atresia and intact ventricular septum. 55. Qureshi SA, Rosenthal W, Tynan M, et al. Transcatheter laser-
J Am Coll Cardiol. 1988;12:719-25. assisted balloon pulmonary valve dilation in pulmonary valve
39. Silove E, de Giovanni J, Shiu M, et al. Diagnosis of right atresia. Am J Cardiol. 1991;67:428-31.
ventricular outflow obstruction in infants by cross-sectional 56. Parsons JM, Rees MR, Gibbs JL. Percutaneous laser valvoto-
echocardiography. Br Heart J. 1983;50:516-20. my with balloon dilatation of the pulmonary valve as primary
40. Trowitzsch E, Colan S, Sanders S. Two-dimensional treatment for pulmonary atresia. Br Heart J. 1991;66:36-38.
echocardiographic evaluation of right ventricular size and 57. Latson LA. Nonsurgical treatment of a neonate with pulmonary
function in newborns with severe right ventricular outflow atresia and intact ventricular septum by transcatheter puncture
obstruction. J Am Coll Cardiol. 1985;6:388-93. and balloon dilation of the atretic valve. Am J Cardiol.
41. Alwi M, Choo KK, Latiff HA, et al. Initial results and medium- 1991;68:277-9.
term follow up of stent implantation of patent ductus arteriosus 58. Agnoletti G, Piechaud JF, Bonhoeffer P, et al. Perforation
in duct-dependent pulmonary circulation. J Am Coll Cardiol. of the atretric pulmonary valve. J Am Coll Cardiol.
2004;44(2):438-45. 2003;41:1399-403.
42. Michel-Behnke I, Akintuerk H, THul J, et al. Stent 59. Humpl T, Sőderberg B, McCrindle BW, et al. Percutaneous
implantation in the ductus arteriosus for pulmonary blood balloon valvotomy in pulmonary atresia with intact
supply in congenital heart disease. Catheter Cardiovasc Interv. ventricular septum–impact on patient care. Circulation.
2004;61:242-52. 2003;108:826-32.
43. Ashburn DA, Blackstone EH, Wells WJ, et al. Determinants of 60. Gibbs JL, Blackburn ME, Uzun D, et al. Laser valvotomy
mortality and type of repair in neonates with pulmonary atresia with balloon valvuloplasty for pulmonary atresia with
and intact ventricular septum. J Thorac Cardiovasc Surg. intact ventricular septum: five years experience. Heart.
2004;127:1000-08. 1997;77:225-28.
44. Odim J, Laks H, Plunkett MD, et al. Successful management 61. Petrucci O, O’Brien SM, Jacobs ML, et al. Risk factors for
of patients with pulmonary atresia with intact ventricular mortality and morbidity after the neonatal Blalock Taussig
septum using a three tier grading system for right ventricular shunt procedure. Ann Thorac Surg. 2011;92:642-52.
hypoplasia. Ann Thorac Surg. 2006;81:678-84. 62. Schneider M, Zartner P, Sidiropoulos A, et al. Stent implantation
45. Yoshimura N, Yamaguchi M, Ohashi H, et al. Pulmonary of the arterial duct in newborns with duct-dependent circulation.
atresia with intact ventricular septum: strategy based on right Eur Heart J. 1998;19:1401-09.
ventricular morphology. J Thorac Cardiovasc Surg. 2003;126: 63. Gewillig M, Boshoff DE, Dens J, Mertens L, benson LN.
1417-26. Stenting the neonatal arterial duct in duct-dependent pulmonary
46. De Leval M, Bull C, Stark J, et al. Pulmonary atresia and intact circulation: new techniques, better results. J Am Coll Cardiol.
ventricular septum: surgical management based on revised 2004;43:107-12.
classification. Circulation. 1982;66:272-80. 64. Mair DD, Julsrud PR, Puga FJ, et al. The Fontan procedure
47. Rosenthal E, Qureshi SA, Chan KC, et al. Radiofrequency- for pulmonary atresia with intact ventricular septum: operative
assisted balloon dilation in patients with pulmonary and late results. J Am Coll Cardiol. 1997;29:1359-64.
valve atresia and on intact ventricular septum. Br Heart J. 65. Najm H, Williams WG, Coles JG, et al. Pulmonary atresia
1993;69:347-51. with intact ventricular septum: results of the Fontan procedure
48. Justo RN, Nykanen DG, Williams WG, et al. Transcatheter [abstract]. Circulation. 1995;92(Suppl I):I-55A.
perforation of the right ventricular outflow tract as initial therapy 66. Reddy VM, Mc Elhinney DB, Silverman NH, et al. Partial
for pulmonary valve atresia and intact ventricular septum in the biventricular repair for complex congenital heart defects: an
newborn. Cathet Cardiovasc Diagn. 1997;40:408-13. intermediate option for complicated anatomy or functionally
49. Hawkins JA, Thorne JK, Boucek MM, et al. Early and late borderline right complex heart. J Thorac Cardiovasc Surg.
results in pulmonary atresia and intact ventricular septum. J 1998;116:21-27.
Thorac Cardiovasc Surg. 1990;100:492-97. 67. Van Arsdell GS. One and one half ventricle repairs. Pediatric
50. Shaddy RE, Sturtevat JE, Judd VE, et al. Right ventricular Cardiac Surgery Annual of the Seminars in Thoracic and
growth after transventricular pulmonary valvotomy and Cardiovascular Surgery. 2000;3:173-78.
central aortopulmonary shunt for pulmonary atresia and intact 68. Maluf MA, Carvalho AC, Carvalho WB. One and a half
ventricular septum. Circulation. 1990;82(Suppl IV):157-63. ventricular repair as an alternative for hypoplastic right
51. Cole RV, Muster AJ, Lev M, Paul MH. Pulmonary atresia with ventricle. Rev Bras Cir Cardiovasc. 2010;25(4):466-73.
intact ventricular septum. Am J Cardiol. 1968;21:23-31. 69. Daubeney PEF, Wang D, Delany DJ, et al. Pulmonary atresia
52. Trusler GA, Yamamoto N, Williams WG, et al. Surgical with intact ventricular septum: predictors of early and medium-
treatment of pulmonary atresia with intact ventricular septum. term outcome in a population-based study. J Thorac Cardiovasc
Br Heart J. 1976;38:957-60. Surg. 2005;130:1071-78.
53. Steinberger J, Berry JM, Bass JL, et al. Results of right 70. Starnes VA, Pitlick PT, Bernstein D, et al. Ebstein’s anomaly
ventricular outflow patch for pulmonary atresia with intact appearing in the neonate: a new surgical approach. J Thorac
ventricular septum. Circulation. 1992;86(Suppl II):167-75. Cardiovasc Surg. 1991;101:1082-7.
592
71. Salvin JW, McElhinney DB, Colan SD, et al, Fetal tricus-
pid valve size and growth as predictors of outcome in pul-
of, and outcomes for, a cohort of 210 consecutive patients.
Cardiol Young. 2004;14:299-308.
40
monary atresia with intact ventricular septum. Pediatrics. 74. John AS, Warnes CA. Clinical outcomes of adult survivors of
593
http://vip.persianss.ir
C hapter
http://vip.persianss.ir
8
the left-sided conus. Since, the VSD is almost always
subaortic in these cases, it is considered amenable to
Cyanotic Heart diseases
corrective surgery.7
Associated Anomalies
Pulmonary Stenosis
Pulmonary stenosis is commonly seen in association with
DORV with subaortic VSD or doubly-committed VSD. It
occurs in approximately 70% of patients with malposition of
great arteries. It is not commonly associated with the Taussig-
Bing type of DORV. Though more often the obstruction is at
the infudibulum, obstruction at the valve, annulus and main
pulmonary artery levels may also be seen; pulmonary atresia
has also been reported.2
Figure 4: Double outlet right ventricle with doubly committed
ventricular septal defect. A = Anterior ; Ao = Aorta; IS = infundibular Subaortic Stenosis
septum; P = Posterior; PA = Pulmonary artery; RA = Right atrium;
RV = Right ventricle; SMT= Septomarginal trabeculation. As described earlier, subaortic obstruction is seen in about a third
of the cases of DORV with subpulmonary VSD. The subaortic
obstruction may be caused by the narrowed left ventricular
Doubly-committed ventricular septal defect: It is reported outflow tract (LVOT), AV valve tissue or accessory valve tissue.
in 10 percent of patients with DORV, who have been surgically Aortic arch obstruction may be present in such patients.2
treated.2 The VSD lies beneath the aortic and the pulmonary
valves (Figure 4). The pulmonary and aortic valves are conti Coronary Artery Anomalies
guous as the infundibular septum is absent. The conus may be
deficient bilaterally or a single conus may be present beneath In DORV, the left coronary artery arises more posteriorly
both the great arteries. and the right coronary artery arises more anteriorly. When
the aorta is right and anterior, the coronary artery anatomy
Great Artery Relationship appears similar to that of TGA with RCA arising from the
posteriorly facing sinus and the LCA arising from the anterior
The great artery relationships fall into two basic categories, facing sinus.2 The origin and proximal course of the coronary
spiraling normally related great arteries or parallel great arteries vary depending on the proximity of the facing sinuses
arteries. This classification is important to determine the to the atrioventricular or the interventricular grooves.11 Single
appropriate type of corrective surgery. coronary artery has been reported in upto 11 percent of the
patients with DORV.12 In all cases of DORV with L-malposition
Normally Related Great Arteries of the great vessels, the right coronary artery passes anterior to
the pulmonary outflow tract, which is of surgical significance.7
The great arteries are normally related and spiral around each
other. The aorta is right and posterior to the pulmonary artery. Conduction System
The VSD in these cases is usually subaortic.2
In DORV, the AV node lies in the usual position of the AV
Parallel Great Artery Relationships septum. The bundle of His lies along the posteroinferior
margin of the VSD in DORV with juxtatricuspid defects like
i. Rightward and side-by-side aorta: The VSD is usually the subaortic, subpulmonary and doubly-committed VSDs.
subpulmonary. When the defect is separated by muscular tissue from the
ii. Right and anterior aorta: In a study by Guo et al, in 50 tricuspid valve, the bundle runs within the muscular tissue and
percent of angiographically studied patients, the aorta is not present at the posteroinferior part of the VSD.2
was either directly to the right or right and anterior to
the pulmonary artery.10 Clinical Presentation
iii. Aorta directly anterior to the pulmonary artery.
596 iv. Left and anterior aorta (L–malposition): This is the least The clinical manifestations of DORV vary depending on the site
common great artery position. The aorta arises from of the VSD, relationship of the great arteries to each other and to
41
the VSD and the presence or absence of stenosis of the semilu-
nar valves. The clinical presentation of DORV may be classified
VSD Type
VSD type (DORV with subaortic VSD without pulmonary
stenosis, DORV with doubly-commited VSD without pulmo
nary stenosis). The blood from the left ventricle is directed
into the aorta through the VSD. Hence, the presentation
is similar to children with a large VSD and pulmonary
hypertension. These children present with poor feeding
and poor weight gain. They may have mild cyanosis or no
Figure 5: Parasternal long-axis shows double outlet right ventricle with
cyanosis at all. These children are likely to develop early large nonrestrictive ventricular septal defect with pulmonary stenosis.
pulmonary arterial hypertension. Ao = Aorta; LA = Left atrium; LV = Left ventricle; PA = Pulmonary
artery; RA = Right atrium; RV = Right ventricle.
TOF Type
TOF type (DORV with subaortic VSD and pulmonary stenosis, border of the cardiac silhouette shows a bulging vascular
DORV with doubly-commited VSD and pulmonary stenosis). shadow with no discrete pulmonary segment observed.7,10
The clinical picture is similar to that of TOF. Cyanosis is Two-dimentional echocardiography shows both great
present from early months of life; a systolic murmur is audible arteries arising from the anterior RV. The features in parasternal
in the new born period. These children may have progressively long-axis view (Figure 5) are inability to identify a great
worsening cyanosis with cyanotic spells. artery arising from the left ventricle and the lack of continuity
between the anterior mitral leaflet and any semilunar valve
TGA Type caused by the conus. The conus is seen either as a dense echo
(fibromuscular) or as a muscular conus separating the two
TGA type (DORV with subpulmonary VSD without pulmonary valves and producing a separation and a more superior postion
stenosis). The clinical presentation is similar to that of TGA of the semilunar valve.13 There is no other outflow to the left
with VSD. The children are cyanosed in the newborn period ventricle other than the VSD. The left ventricular outflow tract
and develop worsening breathlessness, poor feeding and poor may have a tunnel-like configuration. There is hypertrophy of
weight gain. Associated coarctation may be present and such the RV.
children may present with heart failure in the early newborn Identifying the location of the VSD is essential in
period. planning the type of surgical intervention. Subaortic or
subpulmonary defects can be seen in parasternal or subcostal
Remote VSD Type long and short-axis views. Doubly-committed VSD is seen
as a defect that is nearly equally committed to both the
Remote VSD type: They present like patients with single great arteries. Non-committed VSDs are usually complete
ventricle. Children have mild cyanosis and the pulmonary AV septal defects and isolated or multiple muscular VSDs.
blood flow may be balanced, increased or decreased. These are best seen in the apical or subcostal four chamber
views. A restrictive VSD may be seen as an anatomically
Investigations small defect with turbulent flow and causes LVOT
obstruction. The degree of restriction may be assessed by
Electrocardiogram shows right ventricular hypertrophy doppler echocardiography.14
and in some cases biventricular hypertrophy. Conduction In the parasternal short-axis view, the features are
abnormalities may be found.9 simultaneous imaging of both great arteries in an anterior
Chest X-ray findings vary widely depending on the type of location and lack of a clockwise wrap around of the aorta by
DORV. At one end of the spectrum, radiological features may the right ventricular outflow tract. A double-circle appearance
resemble that of VSD with moderate enlargement of the heart of the great arteries may be seen. The great arteries may be
with varying degree of increased vascularity. At the other end, side-by-side, D-malposed or L-malposed.15
the heart may be 'boot-shaped' with decreased vascularity Transesophageal echocardiography (TEE) would furnish
resembling TOF. In DORV with L-malposition, the left upper extra details about the position of the VSD and its relationship 597
http://vip.persianss.ir
8
to the great arteries. Longitudinal planes would delineate Angiographic Illustrations
the right and left ventricular outflow tracts and the great
Cyanotic Heart diseases
arteries. These views demonstrate the typical features of There are 16 possible variations of DORV based on the great
the predominant commitment of both great arteries to the artery relationships and the location of the VSD and it may be
RV. Additional defects of the AV valves and their chordal associated with pulmonary stenosis or with pulmonary artery
attachments may also be delineated well by TEE. hypertension (Figures 7A and B). The various illustrations
Fetal echocardiography: Careful visualization of the four include a case of dextrocardia with situs inversus with DORV
chamber view and outflow tracts in fetal echocardiography (Figures 8A and B).
is diagnostic.16 The VSD is almost always seen in the four The side-by-side relationships of the great arteries with
chamber view. While viewing the outflow tracts, both the subaortic VSD is the most frequently encountered type of
great vessels are seen arising from the RV and are often seen DORV (Figure 9A). The aorta is to the right of the pulmonary
to be side-by-side (Figure 6). artery (Figure 9B). The aortic valve and the pulmonary valve
are at approximately the same horizontal level. The VSD is
the only outlet from the LV, hence it is an obligatory shunt. To
do the LV angiogram one has to have a patent foramen ovale
or an atrial septal defect (Figure 10) or a large VSD.
The true subpulmonary VSD, the Taussig-Bing anomaly,
is relatively rare. The great arteries are in a side-by-side
relationship (Figure 11). Because pulmonary stenosis does not
occur in these cases, the pulmonary trunk is markedly dilated.
The VSD is anterosuperior (supracristal) and immediately
subjacent to the pulmonary valve (subpulmonary VSD).
The right ventricular angiogram demonstrates that the great
arteries are in a side-by-side relationship The classic finding
on the early phase of the right ventricular angiogram is a high
VSD related directly to the pulmonary valve.
The doubly committed, subaortic and subpulmonary, VSD
is closely related to both semilunar valves and lies in a superior
position, The VSD is quite large and extends in an oblique
course beneath both great arteries. On angiogram one cannot
Figure 6: Fetal echocardiography outflow tract view shows double differentiate this type from the Taussig-Bing anomaly because
outlet right ventricular with subpulmonary ventricular septal defect on the lateral view of the RV this VSD is high, anterior,
(Taussig-Bing). Ao = Aorta; LV = Left ventricle; PA = Pulmonary artery;
RV = Right ventricle; VSD = Ventricular septal defect. superior and directly related to both semilunar valves. It is
A B
Figures 7A and B: A. Right ventricle (RV) angiogram shows simultaneous opacification of both the great arteries with post stenotic dilatation
of main pulmonary artery; B. RV angiogram in double outlet RV with pulmonary hypertension shows simultaneous opacification of both the
598 great arteries with dilatation of pulmonary artery due to pulmonary hypertension. Ao = Aorta; LV = Left ventricle; MPA = Main pulmonary artery;
PA = Pulmonary artery.
41
A B
Figures 9A and B: A. Left ventricle (LV) angiogram in frontal view in a case of double outlet right ventricle with large ventricular septal defect
(VSD) (right heart catheter has entered LV through the VSD) illustrates the side-by-side relationship of the great arteries with both the pulmonary
valve (PV) and the aortic valve (AV) at the same level; B. LV angio in a frontal view shows VSD committed to the aorta (Ao) and aorta is to the
right of the pulmonary artery (PA)
impossible to recognize whether the VSD is related to the The relationship of the great arteries may be observed i.e.
pulmonary valve or to both semilunar valves. aorta right and anterior or aorta to the right of pulmonary valve,
The DORV with remote VSD, as a case with multiple VSDs aorta anterior to the pulmonary valve, aorta left and anterior
not committed to both the great arteries, is illustrated in Figure to the pulmonary valve.10 In DORV with L-malposition,
12. The angiographic findings other than the great artery aortography shows left sided anterior ascending aorta with
relationships, are not different from those observed with side- right coronary artery passing anterior to the pulmonary
by-side great arteries and remote VSD. The malposition of the valve.7
aorta can be seen in both frontal and lateral views (Figure 13 A Computed tomography angiography and magnetic
and B). The left ventricular angiogram also demonstrates that resonance imaging: The spatial relationship between semilunar
the VSD is the only outlet from the left ventricle. valves and VSD can be accurately assessed by CT angiography
599
http://vip.persianss.ir
8
Cyanotic Heart diseases
Figure 10: Right heart catheter through atrial septal defect entered Figure 11: Left ventricle (LV) angiogram in left anterior oblique view
left ventricle (LV). The LV angiogram in left lateral view shows the illustrates subpulmonic ventricular septal defect opacifying dilated
ventricular septal defect committed to the aorta (Ao) pulmonary artery (PA) more than the aorta (Ao), that is to the right and
anterior (Taussig-Bing anomaly)
Figure 12: The left ventricle (LV) angiogram in left lateral view illustrates two ventricular septal defects (VSDs) opacifying the trabeculated
right ventricle (RV), in turn opacifying both the great arteries simultaneously, indicating that VSDs are not committed to both the great arteries.
Ao = Aorta; PA = Pulmonary artery.
600
A B
Figures 13 A and B: Right ventricle (RV) angiogram in double outlet RV (DORV) with malposed side by side great arteries, running parallel to
each other. B:RV angiogram in DORV with anterio-posterior malposition of the great arteries
41
http://vip.persianss.ir
8
a liberal VSD patch and if required RVOT patching to allow mortality and in the current era associated arterial switch
unobstructed right ventricular outflow, can be done. If the has reduced the mortality by reducing the complexity of the
Cyanotic Heart diseases
override is excessive and there is annular narrowing, then a tunnel. A DORV with subaortic VSD has a current mortality
transannular patch or an RV to pulmonary artery conduit (all of that of a VSD or a tetralogy repair. The introduction of the
the more if there are major coronaries crossing the RVOT) arterial switch for the Tausig-Bing anomaly has reduced the
may need to be implanted. mortality from as high as 50 percent to 5–15 percent.
603
http://vip.persianss.ir
C hapter
42 Truncus Arteriosus
Truncus Arteriosus
incidence of persistent truncus arteriosus.9 nature of pulmonary artery anatomy and are discussed below.
3. Cardiac neural crest cells express PAX3 gene: PAX3
gene mutation may be responsible for development of Ventricular Septal Defect
truncus arteriosus. However, the basis of the types of
truncus arteriosus cannot be explained with this theory, at Conal septal or infundibular VSD is the rule. In echocardio
this time.10 Several other candidate genes have also been gram, it appears as though the single truncal valve overrides
proposed as etiology for truncus arteriosus. the ventricular septum. The septal band is intact and so, is part
VSD accompanies truncus arteriosus in almost all cases, of the membranous ventricular septum. Therefore, typically
except for very rare reports.7 Typically the VSD in truncus this is a conal septal VSD—just as in tetralogy of Fallot.
arteriosus is a conal septal defect and is large in size. The Distal infundibular septum is defective resulting in a large
ventricular septum appears malaligned in an echocardiogram, VSD. The right posterior/inferior division and left anterior/
due to the single truncal valve overriding the VSD. Typically, superior division of the septal band form the inferior border of
the VSD does not involve the membranous portion of the the VSD. There have been only two of 47 cases, reported by
ventricular septum. This portion of ventricular septum is van Praagh,7 which did not have a VSD.
usually intact leaving a piece of ventricular septum separating
the edge of the conal septal VSD and tricuspid valve annulus. Pulmonary Arteries
There may be associated abnormalities of tricuspid valve
including its anterior leaflet and medial papillary muscle, The main pulmonary artery (PA) usually arises from the left
coronary arteries, pulmonary arteries and aortic arch branches. posterolateral portion of the common arterial trunk (as in
type I). The right and left pulmonary arteries may arise from
GENETIC ASSOCIATIONS back (as in type II) or side (as in type III) of common arterial
trunk directly. When the right and left pulmonary arteries have
Conotruncal anomaly is one of the better-studied areas separate origins, one of the pulmonary arteries may be absent;
of cardiovascular developmental genetics. There is a seen in 16 percent cases in one series.15 In the Mayo clinic
high association with DiGeorge syndrome with 22q11 series, in 80 percent of cases with single pulmonary artery, the
microdeletion identified using fluorescent in situ hybridization pulmonary artery was absent on the side of aortic arch. This
(FISH) technique. Reviewed by multiple authors,11-14 22q11 is in contradistinction to what is noted in tetralogy of Fallot,
microdeletion is noted in 20 to 33 percent of patients with where when a PA is absent, it will be on the side opposite from
truncus arteriosus. There is a high association with right that of aortic arch.
aortic arch. Of the 251 patients who were screened for 22q11, Pulmonary artery after its origin may criss-cross in cases of
microdeletion was positive in 50 percent of patients with truncus arteriosus coexisting with interrupted aortic arch, i.e.
interrupted aortic arch, 35 percent of truncus arteriosus and left PA originates to the right of right PA and crosses to the left
16 percent of tetralogy of Fallot.14 Similarly, five of 15 (33%) side.16
consecutive patients with truncus arteriosus were positive for
22q11 detection.11 Associated features in DiGeorge syndrome Truncal Valve
include dysmorphic facies, thymic and parathyroid hypoplasia,
skeletal and renal abnormalities and developmental delay. Most commonly, truncal valve has three leaflets (67%).
Velocardiofacial syndrome is another genetic association Quadricuspid truncal valve occurs in 24 percent of cases.
characterized by presence of facial features including cleft lip Bicuspid truncal valve is noted in 7 percent. Unicuspid
and palate, learning difficulties and heart defect. truncal valve has been rarely reported. When there are three
or four leaflets, they are usually similar in size. Truncal valve
PATHOLOGY regurgitation is more common, while truncal valve stenosis
is rare.7
Common Arterial Trunk
Coronary Ostial Anomalies
Presence of a single arterial trunk originating from base of
the heart is the hallmark of this defect. The pulmonary artery Location of the coronary ostia may be abnormal; the most
originates from the common arterial trunk either as a common common abnormality being a high-origin of the coronary
(main) pulmonary artery first and then branch into right and artery and location above the wrong commissure or cusp.
left pulmonary arteries or the right and left pulmonary arteries Rarely, coronary ostial stenosis has been noted.
605
http://vip.persianss.ir
8
Aortic Arch Table 1
Incidence of associated anomalies in truncus arteriosus.
Cyanotic Heart diseases
Right aortic arch is present in 33 percent of cases.2,7 (Compiled from Kirklin and Barrat-Boyes,18 Russell HM, et al,19
Bohuta, et al20 and Goldmunz12.
Ventricles
therefore, there is partial separation of aorta and main PA.
Right ventricular (RV) hypertrophy and enlargement are Distal to the origin of main PA from the common arterial
always present. Left ventricular (LV) outflow is usually trunk, both aorta and main PA are identifiable. Short segment
normal. VSD usually is large. However, in rare occasions, of main PA gives rise to both branch pulmonary arteries.
VSD can be restrictive. If the overriding truncal valve is This type is seen in 48 to 68 percent of cases. Type II—no
committed primarily to the right ventricle, thus resembling main PA is present. Branch pulmonary arteries arise from the
a posterior deviation of the ventricular septum, there is a back portion of the common arterial trunk very close to each
potential to develop LV outflow tract obstruction when VSD other. This type is seen in 29 to 48 percent. Type III—no main
is closed. Such VSD may need enlargement during surgical PA is noted. The two branch pulmonary arteries arise from
repair. Significant truncal valve regurgitation is also a reason the side of the common arterial trunk. This type is seen in
for LV enlargement. 6 to 10 percent of cases.21 Type IV—there is no main PA.
Branch pulmonary arteries arise from different parts of the
Associated Defects aorta. This type is also called pseudotruncus and is thought to
be part of pulmonary atresia with VSD.21 Commonly the left
Associated cardiac defects include right aortic arch, interrupted PA originates from the undersurface of the arch and right PA
aortic arch, atrial septal defect, persistent left SVC and others originates from mid-thoracic descending aorta, approximately
(Table 1).11,18-20 Normal pulmonary venous return was seen from the level of lung hilum.
in all, but one of 47 cases in Van Praagh series.7 Associated
noncardiac defects occurred in approximately 21 percent of Classification 2 (1965)
cases, as seen in Van Praagh series.7
Van Praagh classification7 is somewhat more complex.
CLASSIFICATION Initially, truncus arteriosus is classified on the basis of
presence or absence of VSD; type A—with VSD. Type
Even though several classifications exist, two classifications B—without VSD. Since there have been very rare reports
of truncus arteriosus have been commonly followed. Collett of truncus arteriosus without VSD, type B is practically
and Edwards6 classification is more widely used than that of nonexistent, except for the rare, single cases reported in the
Van Praagh.7,8 literature. Type A is subdivided into four subtypes (Figure 1,
middle). A1—main PA arises from the common arterial trunk
Classification 1 (1949) and then, bifurcates into branch pulmonary arteries (similar
to type I of Collette and Edward classification). A2—absence
Collett and Edward classification6 is based on the degree of of main PA. Branch pulmonary arteries arise directly from
main PA development and of the origin of pulmonary arteries the common arterial trunk. Type A2 includes type II and
606 (Figure 1, top): Type I—the spiral septum is partially formed, III of Collette and Edward classification. Type A3—left PA
42
Truncus Arteriosus
Figure 1: Diagram illustrating various classifications described, including those of Collett and Edwards,6 Van Praagh,7 Modified Van Praagh8
(Adopted in ‘Nomenclature Project’ 200022) and the most recent ‘Simplified’19. See text for detailed description
originates from aortic arch. Right PA originates from the Classification 4 (2011)
common arterial trunk. Type A4 —truncus arteriosus with
interrupted aortic arch. Descending aorta receives blood flow Very recently, a simplified categorization of common arterial
from a persistent ductus arteriosus. trunk has been proposed by the surgical group in Chicago, in
Types A1 to A3 display well-developed branchial arch four collaboration with Prof RH Anderson.19 This group proposes to
and poorly developed arch six. This results in absent Patent classify truncus arteriosus into only two categories, namely aortic-
ductus arteriosus (PDA). Type IV displays a poorly developed dominant or pulmonary-dominant types (Figure 1, bottom). This
arch four and well-developed arch six leading to hypoplasia, is based on the observation that among the 28 autopsy specimens
coarctation, or interruption at the level of aortic isthmus and a examined, 20 specimens were aortic-dominant. Pulmonary-
large PDA. Since type A4 is rare, presence of PDA in truncus dominance was less common and was associated with presence
arteriosus is an uncommon finding. Overall, PDA was present of a discrete aorta, which was hypoplastic and a PDA supplied
in 30 percent of cases with truncus arteriosus. However, PDA majority of flow to the descending aorta. In addition, only in the
is commonly noted, when there is associated arch hypoplasia, pulmonary-dominant category, did the pulmonary arteries arise
coarctation or interruption of aorta. Thus, when there is a from the side of common truncus and the aortic component is
large aorta present, PDA is usually absent (91%). Conversely, identifiable as a discrete structure within the pericardial cavity.
PDA was present in all cases with small aorta with or without Incidence was similar in 42 clinical case series from Chicago, in
coarctation or interruption.7 which 38 were aortic-dominant type and four were pulmonary-
dominant type. Even though this classification is simplified, it is
Classification 3 (2000) fairly new and has not come into clinical use.
Figure 1 summarizes the above classifications. The
Congenital Heart Surgery Nomenclature and Database Project, preference of the authors of this chapter is Collett and
200022 proposes a unified classification (Figure 1, middle). Edwards’ classification.
607
http://vip.persianss.ir
8
Clarification of Related Terminology respiratory distress occurs due to bronchial compression
from dilated common trunk, especially when associated
Cyanotic Heart diseases
Pseudotruncus is a term introduced by Bharati and associates with interrupted aortic arch (usually right main bronchus) or
in 1974.21 The term refers to type IV truncus in Collett and between anteriorly placed left pulmonary artery and posterior
Edwards’ classification, in which pulmonary arteries originate portion of aortic arch (usually left upper lobe bronchus). Babies
from descending thoracic aorta. This also refers to the subtype with interrupted aortic arch or coarctation of aorta may present
of pulmonary atresia with VSD, where pulmonary arteries precipitously when the ductus arteriosus closes in the neonatal
are discontinuous and arise from aortic arch and descending period. Such patients may constitute approximately 10 percent
thoracic aorta, respectively. These may be aortopulmonary of the patients with truncus arteriosus. Manifestations would
collateral arteries rather than native pulmonary arteries. Use of include circulatory collapse, metabolic acidosis, respiratory
this term is discouraged in the nomenclature project paper.22 distress and cyanosis. Absent femoral pulse will be part of the
Hemitruncus refers to a condition with origin of a physical finding.
pulmonary artery from ascending aorta. Again, use of this Mild cyanosis may be present from decreased pulmonary
term is discouraged in preference to more specific description blood flow due to either pulmonary artery ostial stenosis or high
of the lesion. This also probably is a subtype of pulmonary pulmonary vascular resistance, that is usual in neonatal period.
atresia with VSD with major aortopulmonary collateral Cyanosis resolves when the pulmonary vascular resistance
arteries rather than a subtype of truncus arteriosus. decreases with transition to neonatal circulation. Features of
Use of both pseudotruncus and hemitruncus are also increased pulmonary blood flow and heart failure will develop
strongly discouraged by the authors of this chapter due to lack as the baby gets older, unless severe anatomic stenoses of
of developmental basis for these terms. pulmonary arteries keep the pulmonary blood flow at a low
level. Recurrent respiratory infections and failure to thrive
NATURAL HISTORY occur just as with other infants with large left-to-right shunting.
In older children, cyanosis develops again as Eisenmenger
Natural history for survival without intervention is poor syndrome occurs with development of pulmonary vascular
in children with truncus arteriosus. Without surgical repair, obstructive disease.
only 50 percent survive beyond 1 month, 30 percent survive
beyond 3 months, 18 percent survive beyond 6 months and Physical Examination
12 percent survive beyond 1 year.18 Cause of death during
neonatal period is congestive heart failure from large left Large volume pulse due to diastolic reversal of flow in the
to right shunting and/or truncal valve regurgitation. Some aorta from continued diastolic flow into the pulmonary arteries
patients develop endocarditis or brain abscess, causing their may easily be detected. Hyperdynamic precordium occurs.
death.6 Children who survive to 1 year of age do so, because Precordial bulge occurs due to right ventricular enlargement
of pulmonary artery stenosis and therefore, partial or complete and hypertrophy. Signs of respiratory distress occur with large
protection of the pulmonary vasculature from exposure to left-to-right shunting. However, if the pulmonary blood flow
systemic arterial pressure and consequent decreased risk for is normal or diminished due to anatomic pulmonary artery
development of pulmonary hypertensive vascular changes. stenosis or persistence of high pulmonary vascular resistance,
Therefore, there is low mortality after 1 year in this subgroup the child will present without features of heart failure or
of patients. Very few patients survive infancy and early respiratory distress. There may be mild cyanosis, however.
childhood with significant left-to-right shunting and yet, not Auscultation reveals normal to loud S1. Systolic click will
develop pulmonary vascular disease. This constitutes half of be present from truncal valve abnormalities or dilated common
survivors beyond 1 year or <5 percent of all infants born with arterial trunk. Second sound will be single. Systolic ejection
truncus arteriosus.23 When pulmonary vascular obstructive murmur with or without a thrill from pulmonary artery stenosis
disease (pulmonary vascular resistance > 9 Woods units m2) or truncal valve stenosis may be present. Similar murmur is also
develops during infancy or later, there is good chance for such heard when there is increased pulmonary blood flow through
patients to survive into their teens without surgical repair.24 nonstenotic branch pulmonary arteries. With severe pulmonary
However, pulmonary vascular occlusive disease develops artery stenosis, this murmur may be continuous. Presence of a
gradually and Eisenmenger syndrome eventually occurs, high frequency, early diastolic decrescendo murmur indicates
leading to death. truncal valve regurgitation. This is a discrete murmur although,
may be very low in intensity. This should not be confused
CLINICAL FEATURES with a diastolic rumble from increased pulmonary blood flow,
due to increased flow across the mitral valve; this is a mid-
Presenting symptoms include features of heart failure in the diastolic event. In rare cases of restrictive VSD, VSD murmur
608 first few weeks of life consisting of tachypnea, tachycardia, may be heard. Liver enlargement is present with heart failure,
irritability, poor feeding and poor weight gain. Rarely, secondary to a large left-to-right shunt.
42
DIFFERENTIAL DIAGNOSIS BASED side. In older children with pulmonary vascular disease,
ON CLINICAL FEATURES cardiomegaly and pulmonary plethora diminish with time.
Truncus Arteriosus
Infants with Heart Failure Electrocardiogram
Infants with heart failure usually have mild cyanosis and Normal QRS axis (rightward or normal quadrant) and RV
the differential includes transposition of great arteries with hypertrophy are noted early. LV hypertrophy develops later.
VSD, double outlet right ventricle, tricuspid atresia with large Often, biventricular hypertrophy is present at the time of
VSD (with or without transposition of great arteries), single diagnosis. P pulmonale develops later. Thus, none of the ECG
ventricle without pulmonary stenosis and total anomalous features are diagnostic in truncus arteriosus.25
pulmonary venous return (TAPVR). In tricuspid atresia,
left axis deviation and LV dominance are noted in the ECG. Echocardiography
Paucity of LV forces may be present in ECG in TAPVR.
Absent pulmonary artery segment in chest X-ray will support Echocardiography is the most important study that provides
either truncus or transposition of great arteries. However, the diagnosis, as well as most of the information necessary
there can be a normal-appearing pulmonary artery segment in for surgical planning. In neonates and infants, no further
type I truncus arteriosus, where the small common pulmonary investigations are necessary, unless there were specific
artery segment may produce a PA segment shadow on chest unanswered questions exist after echocardiography.
X-ray. Right aortic arch supports the diagnosis of truncus Objectives of echocardiography include demonstration of
arteriosus. Echocardiographic features are diagnostic for each single great artery from the ventricles, conal septal VSD, over
of the conditions mentioned above. riding truncal valve, truncal valve anatomy, pulmonary arteries,
PDA and other associated anomalies including interrupted
Older Infant and Children with Continuous Murmur and aortic arch, anomalies of the origin of aortic arch branches,
Evidence of Increased Pulmonary Blood Flow abnormalities of coronary artery origins, persistent left SVC,
additional VSDs, tricuspid and mitral valve anomalies,
Aortopulmonary window or PDA should be considered in if any. It is important to differentiate truncus arteriosus
the differential. Mild cyanosis is present in the children from pulmonary atresia with VSD and aortopulmonary
with truncus and may be too subtle to be recognized. Small window.26 Echo findings should enable determination of the
or absent PA segment, if present in chest X-ray will support type of truncus arteriosus and its physiology. Systematic
truncus arteriosus. Echocardiographic features are distinctive. echocardiographic evaluation of truncus arteriosus is well-
described in multiple echocardiography text books such as by
Children with Cyanosis Snider and Ritter.27
Parasternal long-axis view (Figure 2) shows the characteristic
In cyanotic children, differential diagnosis will include conal septal VSD with apparent overriding of aorta (truncus).
tetralogy of Fallot, pulmonary atresia with VSD, tricuspid Inability to show the second outflow tract and valve
atresia, atrioventricular septal defect with pulmonary stenosis (pulmonary valve) is a feature that helps to distinguish this
and double-outlet right ventricle with pulmonary stenosis. entity from tetralogy of Fallot. Anteriorly, the common arterial
Echocardiographic findings are diagnostic. trunk does not have continuity with infundibular septum.
Posteriorly, there is fibrous continuity between truncal valve
NONINVASIVE EVALUATION and mitral valve. The branch pulmonary arteries will be seen
to arise from the posterior and leftward aspect of the common
Chest X-ray arterial trunk. Color Doppler study will provide an assessment
of truncal valve stenosis and regurgitation.
Marked cardiomegaly and pulmonary plethora are present Parasternal short-axis view helps to evaluate truncal valve
in most infants. In type I truncus, there may be a normal PA anatomy regarding number of valve leaflets (Figure 3), stenosis
segment visible. In other types, the PA segment is diminutive or regurgitation. Pulmonary valve is undetectable. Location
or absent, giving the appearance of a narrow superior of the VSD should also be confirmed. Characteristically,
mediastinum. Right aortic arch is noted in approximately the membranous ventricular septum is intact with the conal
33 percent of truncus arteriosus patients. Comma sign in septal area deficient (between 12 O’clock and 2 O’clock in
left upper mediastinal border indicating high origin or high parasternal short-axis view (Figures 4A and B). Overriding
arching of left pulmonary artery may be recognizable in type of the common truncal valve may be unequal across the
III truncus.2 Absent unilateral pulmonary artery from truncus ventricular septal defect creating an impression of anterior
may cause pulmonary oligemia and smaller thorax on that or posterior deviation of the ventricular septum. Posterior 609
http://vip.persianss.ir
8
Cyanotic Heart diseases
A B
Figures 4A and B: A. Parasternal short-axis view showing the
Figure 2: Parasternal long-axis view showing common arterial trunk ventricular septal defect (VSD) (arrow). VSD is conal septal VSD
(TA), ventricular septal defect (arrow) and truncal valve overriding with intact membranous portion of the ventricular septum (arrow);
ventricular septum. LV = Left ventricle; RV = Right ventricle B. Color Doppler imaging shows right-to-left shunting (arrow)
across the conal septal VSD in this echocardiogram performed at
1 day of age, upon presentation with mild cyanosis. LA = Left atrium;
RA = Right atrium; RV = Right ventricle
Truncus Arteriosus
A B
Figures 7A and B: Apical four-chamber view dual frames consisting
of (A) 2D image and (B) color Doppler image obtained by a more
anterior tilt of the transducer from the previous figure. These images
Figure 6: Apical four-chamber view demonstrating a conal septal demonstrate main pulmonary artery (MPA) originating from the left
VSD (ventricular septal defect) with an overriding truncal (T) valve. side of the truncus arteriosus (TA) and bifurcating into right (RPA) and
Differential diagnosis for this appearance would include both truncus left (LPA) pulmonary arteries
arteriosus and pulmonary atresia with VSD. Similar appearance may
be seen in interrupted aortic arch with VSD as well. LV = Left ventricle;
RV = Right ventricle
Objectives of Catheterization
http://vip.persianss.ir
8
for surgical correction. There are practical difficulties in
obtaining representative samples for oxygen saturation and
Cyanotic Heart diseases
Angiography
Ventriculography
Relative sizes, additional VSDs, relationship of VSD to truncal
valve/arterial trunk should be defined.
Diagnosis of Aortic Interruption observations made from echocardiography and during the
catheterization itself.
Diagnosis of aortic interruption can be difficult with
angiography. Attention must be paid to each branch of the Thoracic Aortogram
aortic arch. A large PDA may be mistaken for aortic arch and
the ascending aorta for innominate artery. Confirming the This will show any aortopulmonary collateral arteries to the
position of each of the aortic arch branches helps to correctly lungs—especially, only one PA is identified to originate from
interpret aortic arch anomalies. aorta or truncus.
Truncus Arteriosus
Medical Management
Medical management depends on the status of pulmonary
blood flow. When there is increased pulmonary blood
flow and congestive heart failure, therapy is indicated
to address heart failure. Diuretics and digoxin should be
used in adequate doses. Afterload reducing agents such
as captopril may be used, if necessary. High calorie diet
may be necessary in infants who show signs of increased
pulmonary blood flow and heart failure. For infants and
children who are slightly cyanotic and not have features
of increased pulmonary blood flow, active therapy may not
be necessary. But, close follow- up will be needed, while
waiting for surgery. Surgery may be postponed if the patient
stabilizes and gains weight. But, surgery should preferably
be performed in early infancy for the fear of development of
pulmonary vascular changes. Figure 10: Schematic diagram of surgical repair of truncus arteriosus
consists of separation of pulmonary arteries (PAs) from the common
arterial trunk and connecting the pulmonary arteries to the right
Surgical Management ventricle (RV) via a valved conduit, which is usually a homograft.
Ventricular septal defect closure, which is part of this surgery is not
Palliative procedure, if necessary, will be pulmonary artery shown in this figure. LV = Left ventricle; RA = Right atrium
banding. PA banding may be technically difficult depending
upon the length of the common PA. Banding individual
pulmonary arteries is fraught with difficulty in getting the
appropriate size band for each vessel. Banding of the PA is Postoperative Management
largely abandoned in the current day management. In addition to the usual postoperative care, immediate post
Surgical repair upon diagnosis is the usual approach in operative treatment includes management of episodes of
the current era. Exact timing of surgery may vary depending pulmonary hypertensive crises. Considerable precautions
upon the specific features in each patient. Since the only are taken to avoid pulmonary hypertensive crisis by keeping
approximately 10 percent of patient survive first year without the baby sedated with ample analgesics and sedatives. Some
surgery and there is a risk of rapid development pulmonary institutions routinely use muscle relaxants at least for the first
vascular obstructive changes, surgical repair usually is night of surgery. Nitric oxide is used as needed. Ventilatory
performed in early infancy if not as newborn. strategy to maintain alkalosis and avoiding hypoxia and
Principles of surgery include closure of VSD, separation hypercarbia is instituted.
of the pulmonary arteries from the common arterial trunk and There is also significant morbidity from pulmonary artery
connecting them to RV-PA conduit and closing the defect in stenosis, usually at the distal anastamosis of the conduit—
the common arterial trunk (Figure 10). Usually, truncal valve in the postoperative period. Such stenosis may need cardiac
does not require any surgical intervention, unless there is catheterization and angiography to demonstrate the stenosis.
significant stenosis or regurgitation. Stenting of the distal RV-PA conduit or proximal branch
When there is associated interrupted aortic arch, surgical pulmonary arteries (Figures 11 and 12) is an option in this
repair has to be performed as newborn after initial stabilization period. Balloon angioplasty of such conduit/pulmonary artery
on prostaglandin infusion. Surgical mortality is relatively high, stenosis is not advisable due to fresh suture lines.
when a combined repair of truncus arteriosus and interrupted
aortic arch need to be performed. Presence of truncal valve Outcome of Treatment
regurgitation at presentation greatly worsens the prognosis for
surgical outcome and survival. Surgical options include truncal Early Surgical Outcome
valve repair, truncal valve replacement using homografts or
mechanical valves; these have not produced good results, but In a recent review of Society of Thoracic Surgeons database
may be necessary. between 2000 and 2009 in 63 centers, 572 surgeries had been
613
http://vip.persianss.ir
8
Long-term Surgical Outcome
Cyanotic Heart diseases
Truncus Arteriosus
provided. Follow-up with specialist cardiologist during and percent and at 2 years, 76 percent. Development of PA stenosis
after pregnancy should be done. was considered secondary to surgery rather than preoperative
reason, because the pulmonary arteries were adequate in size
Alternative Surgical Approaches prior to surgery.34
We utilize balloon angioplasty and/or stenting of branch
In a series of 32 patients, 17 had conventional RV-PA conduit and pulmonary arteries and/or the conduit (Figures 13 to 15) to
13 had a conduit created using LA appendage and monocuspid relieve the right ventricular outflow tract obstruction and
valve.33 Mortality rates were similar between these two groups. attempt to reduce the right ventricular pressure to less than
However, reintervention rate at a mean follow-up of 40 months half systemic level. Balloon angioplasty35 and stents36,37
was significantly lower in the ‘non-conduit’ group; five of 11 appear to prolong the life of the conduit and lengthen the
in conduit group had conduit replacement, while only two interval between conduit replacements.
of nine in ‘non-conduit’, group required replacement. Lesser Recently, older candidates with conduit stenosis and/or
RV outflow gradient and better growth of branch pulmonary regurgitation have an option of transcatheter valves such as
arteries were also noted in the ‘non-conduit’ group. Whether Bonhoeffer,38 Melody® (Medtronic, Inc. USA)39 or Edwards
or not this advantage at short-term follow-up33 holds up at a Sapien® (Edward Lifesciences Inc)40 valves. Short-term
longer-term follow-up remains to be seen. results are encouraging for these valves. While transcatheter
A B C
615
Figures 14A to C: Selected cine frames in the lateral view demonstrating stenosis of the conduit (arrow in A), which is wide open
following stent implantation (arrow in C). Stent (St) before the contrast injection is shown in B. RV = Right ventricle
http://vip.persianss.ir
8
conclusion
Cyanotic Heart diseases
Truncal Root Dilatation and Truncal Valve Regurgitation 1. Lev M, Saphir O. Truncus arteriosus communis persistens. J
Pediatr. 1942;20:74.
Truncal root dilatation and truncal valve regurgitation occur 2. Calder L, van Praagh R, van Praagh S, et al. Truncus arteriosus
communis. Clinical, angiographic and pathologic findings in
in most of the patients. In a recent study of a cohort of 78
100 patients. Am Heart J. 1976;92:23.
patients, the mean truncal root diameter Z-score was 5.1 ± 3. Tandon R, Hauck AJ, Nadas AS. Persistent truncus arteriosus.
2.3. No dissection or rupture occurred. However, six patients A clinical, hemodynamic, and autopsy study of nineteen cases.
underwent aortic root surgery for aortic root dilatation Circulation. 1963;28:1050-60.
associated with truncal valve regurgitation and LV dilatation.41 4. Wilson J. A description of a very unusual malformation of the
human heart. Philos Trans R Soc London [Biol]. 1798;18:346.
Myocardial Dysfunction 5. Buchanan A. Malformation of the heart. Undivided truncus
arteriosus. Heart otherwise double. Trans Pathol Soc Lond.
Myocardial Dysfunction may develop from repeated surgical 1864;15:89.
6. Collett RW, Edwards JE. Persistent truncus arteriosus: A
procedures, conduit dysfunction, delayed surgery and myo-
classification according to anatomic types. Surgical Clinics of
cardial ischemia. North America. 1949;29:1245.
7. van Praagh R, van Praagh S. The anatomy of common
Arrhythmias aorticopulmonary trunk (Truncus arteriosus communis) and its
embryologic implications. Am J Cardiol. 1965;16:406-25.
Arrhythmias though rare can occur, also an important disorder 8. Van Praagh R. Editorial: Classification of truncus arteriosus
after surgical repair. communis (TAC). Am Heart J. 1976;92:129-32.
9. Kirby ML. Contribution of neural crest to heart and vessel
morphology. In: Richard P Harvey, Nadia Rosenthal (Eds). Heart
Progressive Pulmonary Vascular Disease Development. San Diego, CA: Academic Press. 1999.pp.179-93.
10. Conway SJ, Henderson DJ, Copp AJ. Pax3 is required for
In patients with delayed detection, pulmonary vascular
616 obstructive disease may develop.
neural crest migration in the mouse: evidence from the splotch
(Sp2H) mutant. Development. 1997;124:505-14.
11. Momma K, Ando M, Matsuoka R. Tuncus arteriosus 28. Rudolph M. Congenital heart diseases of the heart: Clinical-
42
communis associated with 22q11 deletion. J Am Coll Cardiol. physiologic considerations. 2nd edition. Armonk, NY. Futura
Truncus Arteriosus
1997;30:1067-71. Publishing Co. Inc. 2001.pp.737-61.
12. Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of 29. Russell HM, Pasquali SK, Jacobs JP, et al. Outcomes of repair
22q11 deletions in patients with conotruncal defects. J Am Coll of common arterial trunk with truncal valve surgery: a review
Cardiol. 1998;32:492-8. of the society of thoracic surgeons congenital heart surgery
13. Emanuel BS, Budarf ML, Scambler PJ. The genetic basis database. Ann Thorac Surg. 2012;93:164-69.
of conotruncal defects: The chromosome 22q11.2 deletion. 30. Rajasinghe HA, McElhinney DB, Reddy VM, et al. Long-term
In: Heart Development. (Eds). Richard P Harvey and Nadia follow-up of truncus arteriosus repaired in infancy: a twenty-
Rosenthal. San Diego, CA. Academic Press. 1999.pp.463-78. year experience. J Thorac Cardiovasc Surg. 1997;113:869-78.
14. Goldmuntz E. Deciphering the genetic etiology of conotruncal 31. Urban AE, Sinzobahamyya N, Brecher AM, et al. Truncus
defects. In: Artman M, Woodrow Benson D, Srivatsava D, arteriosus: ten-year experience with homograft repair in
Nakazawa M. Malden, MA. Blackwell Futura. 2005.pp.238-41. neonates and infants. Ann Thorac Surg. 1998;66:S183-S8.
15. Mair D, Ritter D, Davis G. Selection of patients with truncus 32. Williams JM, de Leeuw M, Black MD, et al. Factors associated
arteriosus for surgical correction: Anatomic and hemodynamic with outcomes of persistent truncus arteriosus. J Am Coll
considerations. Circulation. 1974;49:144-51. Cardiol. 1999;34:545-53.
16. Butto F, Lucas R, Edwards J. Persistent truncus arteriosus: 33. Raisky O, Ali WB, Bajolle F, et al. Common arterial trunk
Pathologic anatomy in 54 cases. Pediatr Cardiol. 1986;7:95- repair: with conduit or without? Eur J Cardiothorac Surg.
101. 2009;36:675-82.
17. Thiene G, Bortolotti U, Gallucci V. Anatomical study of 34. Lund AM, Vogel M, Marshall AC, et al. Early reintervention
truncus arteriosus communis with embryological and surgical on pulmonary arteries and right ventricular outflow tract after
considerations. Br Heart J. 1976;38:1109-23. neonatal or early infant repair of truncus arteriosus using
18. Kirklin JW, Barratt-Boyes BG. Truncus arteriosus. In: Kirklin homograft conduits. Am J Cardiol. 2011;108:106-13.
JW, Barratt-Boyes BG (Eds). Cardiac Surgery 2nd edition. 35. Rao PS. Balloon dilatation of stenotic bioprosthetic valves. In:
New York: Churchill livingstone. 1992.pp.1131-52. Rao PS (Ed). Transcatheter Therapy in Pediatric Cardiology.
19. Russell HM, Jacobs ML, Anderson RH, et al. A simplified New York, NY: Wiley-Liss. 1993.pp.255-74.
categorization for common arterial trunk. J Thorac Cardiovasc 36. Powell AJ, Lock JE, Keane JF, et al. Prolongation of RV-
Surg. 2011;141:645-53. PA conduit life span by percutaneous stent implantation:
20. Bohuta L, Hussein A, Fricke TA, et al. Surgical repair of intermediate-term results. Circulation. 1995;92:3282-8.
truncus arteriosus associated with interrupted aortic arch: 37. Rao PS. Stents in the management of congenital heart
Long-term outcomes. Ann Thorac Surg. 2011;91:1473-7. disease in the pediatric and adult patients. Indian Heart J.
21. Bharati S, McAllister HA Jr, Rosenquist GC, et al. The surgical 2001;53:714-30.
anatomy of truncus arteriosus communis. J Thorac Cardiovasc 38. Bonhoeffer P, Boudjemline Y, Saliba Z, et al. Percutaneous
Surg. 1974;67:501-10. replacement of pulmonary valve in a right-ventricle to
22. Jacobs ML. Congenital heart surgery nomenclature and pulmonary-artery prosthetic conduit with valve dysfunction.
database project: Truncus arteriosus. ATS. 2000;69:S50-S5. Lancet. 2000;356:1403-5.
23. Juaneda E, Haworth SG. Pulmonary vascular disease in 39. McElhinney DB, Hellenbrand WE, Zahn EM, et al. Short- and
children with truncus arteriosus. Am J Cardiol. 1984;54:1314. medium-term outcomes after transcatheter pulmonary valve
24. Marcelleti C, McGoon DC, Mair DD. The natural history of placement in the expanded multicenter US Melody® valve
truncus arteriosus. Circulation. 1976;54:108. trial. Ciculation. 2010;122:507-16.
25. Victorica BE, Krovetz LJ, Elliott CP, et al. Persistent truncus 40. Kenny D, Hijazi ZM, Kar S, et al. Percutaneous implantation
arteriosus in infancy. Am Heart J. 1969;77:13. of the Edwards SAPIEN transcatheter heart valve for conduit
26. Hagler DJ, Tajik AJ, Seward JB, et al. Wide-angle two- failure in the pulmonary position: Early phase I results from
dimensional echocardiographic profiles of conotruncal an international multicenter clinical trial. J Am Coll Cardiol.
abnormalities. Mayo Clinic Proc. 1980;55:73. 2011;58:2248-56.
27. Snider AR, Serwer GA, Ritter SB. Pesistent truncus arteriosus. 41. Carol WF, McKenzie ED, Slesnick TC. Root dilatation
In: (Eds) Echocardiography in pediatric heart disease. 2nd in patients with truncus arteriosus. Congenit Heart Dis.
edition. St Louis: Mosby. 1997.pp.289-96. 2011;6:228-33.
617
http://vip.persianss.ir
C hapter
Introduction aortic valve anteriorly and to the right. At the same time the
subpulmonary infundibulum fails to develop. TGA is usually
Transposition of the great arteries (TGA) is the most common an isolated defect. Complex TGAs are more likely to be
cause of a cyanotic newborn. Its management has been one of associated with extracardiac anomalies. An Italian multicenter
the amazing success stories as far as the treatment of various study found a 10 percent recurrence risk of congenital heart
complex congenital heart defects in the last two decades is disease (CHD) in families with a child with TGA. This study
concerned. The advances in medical science has converted looked at 370 consecutive patients with TGA. The most
a lesion with a very high mortality if left untreated, to one common CHDs reported were D-TGA, L-TGA, tetralogy of
where the child with TGA today can look forward to having Fallot and VSD.1 The finding of congenitally corrected TGA
a reasonably normal lifestyle and hopefully longevity. This (L-TGA or double discordance) in family members suggest a
treatise will discuss pure or isolated transposition of the common causative gene for these defects. This is against the
great arteries, i.e. a lesion with atrioventricular concordance, traditional classification of D-TGA under conotruncal defect
ventriculoarterial discordance, two good sized ventricles and L-TGA under looping defects.
and atrioventricular valves, with either an atrial septal The genetic mechanisms and several mutations have
defect (ASD), ventricular septal defect (VSD) or patent been implicated as the cause of discordant ventriculoarterial
ductus arteriosus (PDA) as a single associated anomaly or a connections.The genes which maybe involved are the growth
combination of anomalies. differentiation factor-1 gene, the thyroid hormone receptor-
Transposition of the great arteries means that the origin associated protein-2 gene and the gene encoding the cryptic
of the great arteries from the heart is reversed. In simple protein.2
terms, the aorta originates from the right ventricle (RV) and
the pulmonary artery originates from the left ventricle (LV), Incidence
while the atrioventricular (AV) connections are normal (AV
concordance with ventriculoarterial (VA) discordance). Transposition of great arteries is a common form of congenital
Specifically, D transposition of the great arteries implies heart anomaly occurring in 1:2000 to 4500 births and
that the aortic valve is ‘D’ related to the pulmonary valve accounting for 7 to 8 percent of all congenital heart defects.
(to the right and anterior) in the setting of ventriculoarterial Male to female ratio is 2:1, increasing to more than 3:1 for
discordance. However, VA discordance with variable TGA with intact ventricular septum.3,4
semilunar valve relationship has been described. As long as
the pathophysiology and the management pathway is the same ETIOPATHOGENESIS
as classic D-TGA, these variations are still called transposition
of the great arteries. The exact etiology of this disease is still unknown. The
associated risk factors, namely gestational diabetes
Embryology and Inheritance mellitus, maternal exposure to rodenticides, herbicides, and
maternal use of antiepileptic drugs have been postulated.2
Transposition of great arteries is believed to be due to Isolated TGA is called a simple TGA. It could be
abnormal presence and growth of the subaortic infundibulum. associated with a large VSD (up to 45% of cases). The types
This is absent in normal hearts. This infundibulum pushes the of VSDs seen are commonly perimembranous, muscular
and malalignment (30% each). When coarctation or arch Clinical Presentation 43
interruption is associated with TGA it is called a complex
TGA. About 20 percent of isolated TGAs have some form Simple transposition of great arteries usually presents in
Diagnosis
Box 1: Physiological – Clinical classification in In the current era, TGA is diagnosed by transthoracic
transposition of great arteries5 echocardiography. Almost all anatomic features and even
TGA (IVS or small VSD) with increased PBF and small coronary arterial anomalies may be picked up by this imaging
intercirculatory shunting modality. With improvements in fetal echocardiographic
TGA (large VSD) with increased PBF and large intercirculatory techniques, TGA may be diagnosed with certainty in the
shunting fetus as early as 14 weeks of gestation. On echocardiography,
TGA (VSD and LVOTO) with restricted PBF a detailed and complete segmental analysis is essential
TGA (VSD and PVOD) with restricted PBF (Figures 1A to C). Attention to AV valve annulus size,
ventricular size, description of the kind (if any) of
IVS = Interventricular septum; LVOTO = Left ventricular outflow
obstruction; PBF = Pulmonary blood flow: PVOD = Pulmonary subpulmonary obstruction, morphology of the semilunar
vascular obstructive disease; TGA = Transposition of great arteries; valves (especially the pulmonary valve-the future aortic
VSD = Ventricular septal defect. valve), size discrepancy of the main pulmonary artery versus
619
http://vip.persianss.ir
8
Cyanotic Heart diseases
A B
the ascending aorta, coronary artery anatomy (low parasternal assess pulmonary artery pressure and response to vasodilators
window) helps to avoid surprises on the operating table. An in cases of late presentation when a palliative repair is being
anomalous coronary artery can be suspected if in any view, a comtemplated. The derived value of pulmonary vascular
coronary is seen coursing posterior to the pulmonary artery. resistance is fraught with assumptions. Computed tomography/
A few classifications for description of the coronary artery magnetic resonance imaging (CT/MRI) maybe useful and
anatomy exist. We describe the coronary arteries in terms of indicated in those rare cases where an abnormal aortic arch
arising from sinus 1 (leftward sinus) and sinus 2 (rightward (coarctation or interruption) is not visualized to satisfaction.
sinus). The normal coronary artery arrangement would thus A chest radiograph in the neonate with TGA will show a clear
be described as 1LC× 2R. A description in words of what is lung field, normal heart size and a narrow superior mediastinum
seen on echocardiography most often conveys the anatomy (as the great arteries lie on top of each other) (Figure 2). In the
better than complicated classification systems. This is infant, increased pulmonary vascularity and mild cardiomegaly
especially true, when images are suboptimal and there is a will be seen (Figure 3). In fact, severe cyanosis accompanied
suspicion of anomalous coronary. A mention must be made of by (paradoxically) increased pulmonary vascular markings on
any intramural course or juxtacommissural origin. chest radiograph is a pointer to the diagnosis.
It is indeed very rare that cardiac catheterization is done for An electrocardiogram in the neonate may appear normal.
TGA. The indication for cardiac catheterization in TGA is to Gradually, right ventricular hypertrophy manifests as upright
assess LV and RV pressure and suitability for arterial switch in T waves in the right precordial leads along with right axis
patients who present late and noninvasive assessment shows deviation. There may be absence of q waves in the precordial
620 borderline LV size. The only practical indication seems to be to leads (Figure 4).
43
http://vip.persianss.ir
8 Arterial Switch Operation shaped LV cavity in cross-section (interventricular septum
bowing into the LV cavity); posterior wall thickness of less
Jatene arterial switch operation is an open heart surgical than 0.3 cm and LV mass less than 35 g/m2.7 Suitability for
Cyanotic Heart diseases
correction, where the VA discordance is restored to normal. arterial switch surgery is therefore based on LV cavity being
The ascending aorta and the main pulmonary artery are atleast D shaped in systole and LV posterior wall thickness
transected and then anastomosed to the semilunar valve of the being atleast 0.3 cm in diastole. The mass of the LV on 2D
correct ventricle. The coronary artery origins from the original echocardiography is as calculated from the formula:
aortic valve sinuses are mobilized as buttons (ostia surrounded LV mass=1.05 {[5/6A1 (L+t)] – [5/6 A2 L]}
by sinus tissue) and then translocated to a new place on the where 1.05 is the specific gravity of the myocardium. L=long
neoaorta. The Lecompte maneuver brings the main pulmonary axis length of the ventricular cavity obtained from the 4
artery anterior and the ascending aorta posteriorly. Other chamber apical view. t=calculated mean LV wall thickness.
associated lesions like ASD, VSD, PDA and in few cases, t=√(A1/Π) – √(A2/ Π) where A1 is the total area enclosed by
left ventricular outflow obstructions like coarctation, arch the LV epicardium in short axis end diastolic frame. A2 is the
hypoplasia or interruption are also corrected. total area enclosed by the LV endocardium in short axis end
In effect, the arterial switch operation is a very good diastolic frame.
“functional” correction, though not strictly anatomical in In cases of TGA with a large VSD or PDA, the LV does
nature as thought so earlier, as the altered semilunar valve not regress as it remains at a high pressure. Hence in these
relationships, such as being anteroposterior in nature persists situations, ASO could be delayed to around a month or two,
even after the correction. This has a role to play in long-term when the indication would be increasing pulmonary blood
morbidities seen after this corrective surgery. flow and failure to thrive.
In the subset with LVOTO and those found fit for an ASO,
ATRIAL SWITCH OPERATION the LVOTO serves to forestall LV regression and allows an
elective ASO to be carried out.
The other alternative corrective procedures—Senning or There are reports of stretching the age limit of primary
Mustard are the “atrial switch” operations. This is so called ASO in TGA with intact ventricular septum to 3 to 6 months
as the circulatory correction is done at the atrial level, so that of age. These would be instances where the presentation of
the venous blood from the vena cava reaches the pulmonary the infant is late. The risks and mortality are higher and so
artery via the mitral valve and the LV and the pulmonary is the need for some form of left ventricular support for a
venous blood reaches the aorta via the tricuspid valve and time period postoperatively. The long-term behavior of these
the RV. The RV with the tricuspid valve is the systemic ventricles is unknown at the present time. It is hoped that they
ventricle and the mitral valve with the LV is the pulmonary adapt like the neonatal LVs, unlike those “trained” LVs, where
ventricle. Though this serves to correct the hypoxia of TGA, long-term dysfunction is common.
the unphysiological VA relationships give problems in the For the older patients with TGA and large VSD with
long-term in terms of tricuspid valvular regurgitation and pulmonary hypertension, it has been the experience of
systemic ventricular dysfunction along with varieties of the authors that children upto 2 to 3 years of age can be
atrial arrhythmias related to suture lines in the atria. operated upon expecting a low morbidity and mortality post
operatively. For the slightly older children, it has been our
Timing of Surgery practice to measure pulmonary artery pressure directly in the
cardiac catheterization laboratory and see the response of the
In a child with TGA with intact septum, in the normal course pressure to oxygen. A fenestration in the atrial or ventricular
of progression after birth, the LV, which had an equal mass septum is placed in borderline cases. Use of oral pulmonary
with the RV at birth, undergoes regression commensurate with vasodilators (sildenafil, bosentan) postoperatively. has helped.
the fall in the pulmonary vascular resistance. This renders the
LV incapable of supporting the systemic circulation and face Contraindications for an Arterial Switch Operation
the systemic vascular resistance, leading to its failure. Hence,
it mandates that the ASO be performed before the regression
Absolute
of the LV sets in, which is ideally within a fortnight after birth
or atleast by a month of age. Hence the earlier the correction 1. Pulmonary annular stenosis.
is done, the better for the child with TGA and an intact 2. Subvalvar LVOTO, which cannot be resected (non-
septum. It has been observed that babies with small atrial accessory mitral valve tissue).
level communications have better preserved LV myocardium. 3. A deformed pulmonary valve other than a plain bicuspid
This is probably due to the LV seeing more volume of blood valve.
as compared to a situation where there is a large ASD. On 4. A regressed LV seen beyond infancy.
622 echocardiogram, regression of the LV manifests as a banana- 5. Hypoplasia of ventricles.
Relative correcting the TGA physiology by an atrial switch operation 43
or an ASO leaving the VSD untouched could convert them to
Complex coronary artery anatomy. an Eisenmengerized VSD situation, removing the unfavorable
http://vip.persianss.ir
8 3. Neoaortic regurgitation: Approximately 5 to 10 percent, References
the incidence rises over the years. The grade is trivial to
mild in the majority of patients. It is more likely to be 1. Digilio M, Casey B, Marino B, et al. Complete transposition
Cyanotic Heart diseases
severe in patients with complex TGA and in those, who of the great arteries. Patterns of Congenital Heart Disease in
Familial Precurrence. Circulation. 2001;104:2809-14.
have had prior pulmonary artery banding procedure.
2. Martins P, Castela E. Transposition of the great arteries.
4. Coronary artery issues, symptomatic/asymptomatic: Orphanet J Rare Dis. 2008;13:3-27.
Approximately 5 percent. Some centers perform coronary 3. Kouchoukos N, Blackstone E, Hanley F, et al. Cardiac Surgery
angiograms periodically (every 5 years) to assess the growth 3rd edn. Churchill Livingstone, Elsevier; 2003.
and anatomy. Apart from the concern of ischemia, another 4. Sellke Frank, Pedro del NIdo, Scott J Sullivan. Sabiston and
aspect is the disruption of autonomic nervous supply and its Spencer Surgery of the Chest, 8th edn. Saunders Elsevier;
long term impact on vasodilatory capacity during exertion. 2010.
Lifelong follow-up is essential and a thorough annual 5. Wernovsky G. Transposition of the great arteries. In:
physical examination coupled with a 12 lead ECG and a complete Moss and Adams’ Heart Disease in Infants, Children,
and Adolescents: Including the Fetus and Young Adults,
echocardiogram is recommended. At an appropriate age, an
7th edn. Allen HD, Driscoll DJ, Shaddy RE, Feltes TF
exercise stress test should be made an annual requirement. (Eds). Lippincott Williams & Wilkins, Philadelphia; 2008.
pp.1039-87.
Conclusion 6. Liebman J, Belloc NB, et al. Natural history of transposition of
the great arteries. Anatomy and birth and death characteristics.
Isolated TGA as a congenital anomaly can be treated surgically Circulation. 1969;40:237-62.
today with a high degree of success. However, the excitement 7. Lacour-Gayet F, Piot D, Planche C, et al. Surgical
of the arterial switch operation being a “cure” has been management and indications of left ventricular retraining
dampened by the long-term issues being seen as the follow in arterial switch for transposition of the great arteries
with intact ventricular septum. Eur J Cardiothorac Surg.
up has increased. Not withstanding these issues, children with
2001;20(4):824-29.
TGA after the ASO, particularly for simple TGA, can look 8. Sivakumar K, Francis E, Krishnan P, et al. Ductal Stenting
forward to a life of normal growth, activity, with a very good retrains the left ventricle in TGA with IVS. J Thorac Cardiovasc
quality of life and in sinus rhythm, much unlike those with Surg. 2006;132:1081-86.
the atrial switch operations. Recognizing the long-term issues 9. Richard A Jonas. Comprehensive Surgical Management of
encountered, it is mandatory to keep operated children under Congenital Heart Disease. JR Soc Med. 2004;97(8):407-08.
lifelong follow-up. 10. Horer J, Schreiber C, Cleuziou J, et al. Improvement in
long-term after hospital discharge but not in freedom from
There are in fact two things, science and opinion; the former reoperation after the change from atrial to arterial switch
for transposition of great arteries. Thorac Cardiovasc Surg.
begets knowledge, the later ignorance
2009;137:347-54.
—Hippocrates
624
C hapter
Introduction
to a right sided atrium), L-looped ventricles (the morphologic
Congenitally corrected transposition of the great arteries LV with mitral valve positioned on the right) and L-transposed
(ccTGA) is a complex defect remarkable for its significant great arteries (aorta arising off the left-sided morphologic RV
anatomic abnormalities that nonetheless result in hemo and therefore situated anterior and leftward of the pulmonary
dynamically stable physiology. It is a rare defect that combines artery). The RV serves as the systemic ventricle and in the
atrioventricular (AV) discordance with ventriculoarterial absence of other defects, oxygen saturation is normal. The
discordance. In ccTGA the atria are connected to the opposite most common positions of the heart in the chest are levocardia
ventricle (left atrium to right ventricle via a tricuspid valve) (apex to the left) or mesocardia (midline). Patients with levo-or
and the ventricles are connected to the discordant great artery mesocardia and visceral situs inversus have a high likelihood
(right ventricle to aorta). Thus oxygen rich, systemic blood of ccTGA and therefore must carefully be assessed for atrial,
is circulated by the morphologic right ventricle (RV) and ventricular and arterial concordance. Dextrocardia, in which
deoxygenated blood returns to the right atrium to be pumped the apex of the heart is to the right, occurs in approximately 20
out the morphologic left ventricle (LV) to the lungs (Figure 1). percent of patients.1 In cases of dextrocardia with mirror-image
The defect is therefore ‘corrected’ because of the physiologic anatomy the anatomic designation is {I, D, D}.
flow of blood through the body. For the purposes of this review,
univentricular hearts, those with common AV valves and those Associated Defects
with aortic atresia will not be discussed.
The most common associated defects in ccTGA are ventricular
Incidence and Genetics septal defects (VSDs), which occur in 60 to 80 percent of cases,
pulmonary stenosis (PS) in 30 to 50 percent and tricuspid
The incidence of ccTGA in patients with congenital heart valve (TV) anomalies in 14 to 56 percent. The VSDs are
disease (CHD) is approximately 0.5 percent with a slight usually large, perimembranous and subpulmonary in location.
male predominance.1,2 Although a specific genetic defect is Muscular inlet defects as well as multiple VSDs may also be
yet to be defined for ccTGA, the recurrence risk of either type seen. Pulmonary stenosis, more appropriately referred to as
of transposition (corrected or non-corrected) for siblings of left ventricular outflow tract obstruction (LVOTO), may be
ccTGA patients is 2.6 percent. The overall recurrence risk for caused by fibromuscular tissue, valvar stenosis, or aneurysmal
any type of congenital heart defect is 5.2 percent in siblings of tissue of the membranous ventricular septum. The associated
ccTGA patients.2 This recurrence risk of more than 5 percent combination of LVOTO and VSD represents the largest group
is higher than expected, given that the typical recurrence risk of ccTGA patients. TV anomalies can occur along a varied
for unaffected parents to have an additional child with CHD is spectrum. Ebsteinoid malformations of the TV generally
thought to be 1 to 3 percent.3 represent the most clinically severe form. Furthermore, as the
TV is subjected to systemic pressures, even normally formed
Anatomy valves display progressive regurgitation with age. Less
common defects occurring in association with ccTGA include
The most common segmental alignment in ccTGA is that of atrial septal defect, patent ductus arteriosus, pulmonary
{S, L, L}, representing atrial and visceral situs solitus (right-sided atresia, double outlet RV, aortic regurgitation, mitral valve
inferior and superior vena cavae returning deoxygenated blood abnormalities and subaortic stenosis.1,4,5
http://vip.persianss.ir
8 at a rate of approximately 2 percent per year, occurs even in the
absence of surgical repair and is more likely in the presence of
an intact ventricular septum.8,9 Anderson et al10 consistently
Cyanotic Heart diseases
http://vip.persianss.ir
8 Evaluation
Chest Radiograph
Cyanotic Heart diseases
Echocardiography
Transthoracic echocardiography (TTE) as an imaging modality
is relatively inexpensive, widely available and non-invasive.
As with many types of CHD, TTE is the first line and most
useful modality in the diagnosis of ccTGA. The anatomical
designation (most commonly {S,L,L} as discussed previously),
is assigned by demonstrating atrial position, ventricular looping
and arterial looping. Morphology of the RV is seen on TTE by
the presence of coarse trabeculations and a moderator band,
whereas the LV has a smooth-walled endocardium and a
funnel-shaped appearance. The level of the TV is inferior to
the MV, which may also give a clue to ventricular inversion
(Figure 5). In evaluation of the outflow tracts, the aorta in ccTGA
Figure 3A: Chest X-ray of a 6-year-old child with ccTGA and complete is usually anterior and to the left of the PA. Once the diagnosis
heart block. There is levocardia and abdominal situs solitus. The
upper-left cardiac border is straightened secondary to the leftward-
of ccTGA is made through demonstration of discordance
628 between atria and ventricles as well as ventricles and great
positioned ascending aorta. A permanent pacemaker is present with a
transvenous lead situated in the ventricle. arteries, several anatomic objectives should be defined in the
44
Cardiac Catheterization
Rather than a modality for diagnosis, cardiac catheterization
is typically reserved for the postsurgical patient who would
benefit from an intervention such as LV to pulmonary
artery (PA) conduit dilation or stent placement. For patients
undergoing surgical palliation for complex ccTGA anatomy,
catheterization is performed to assess pressure, function,
Figure 5: Transthoracic echocardiogram (apical four-chamber view) in and valve regurgitation prior to surgery (Figures 6A to D).
ccTGA shows the inferior hinge point of the left-sided atrioventricular
valve (TV) opening into a morphological right ventricle (RV). In Most interesting, however, is the adult patient who presents
comparison, the superior level of the right-sided atrioventricular valve with ischemic heart disease and is discovered on cardiac
(MV) hinge point is seen as well as valvar attachments to a papillary catheterization to have ccTGA after abnormal catheter passes
muscle within the morphologic left ventricle (LV) or inversion of coronary arteries on angiography.25
http://vip.persianss.ir
8
Cyanotic Heart diseases
A B
C D
Figures 6A to D: Cardiac catheterization of unrepaired 4-year-old ccTGA patient: A. Morphologic left ventricle (LV), anterior-posterior projection.
A catheter is positioned antegrade from the inferior vena cava and into the right-sided morphologic LV. Contrast fills the LV, main pulmonary artery
(MPA) and pulmonary arteries. There is discrete subvalvar pulmonary stenosis and thickened pulmonary valve leaflets; B. Lateral projection.
Contrast from the LV flows through the posteriorly positioned, stenotic LV outflow tract, across the pulmonary valve, and fills the pulmonary
arteries; C. Morphologic right ventricle (RV), anterior-posterior projection. A catheter is positioned retrograde in the aorta (Ao) and into the
left-sided morphologic (RV). Contrast fills the trabeculated RV, the aorta and descending aorta (dAo). Closed-arrows indicate the circumflex
artery. The left anterior descending coronary artery is not seen in this still frame image; D. Lateral projection. Contrast fills the RV, ascending,
and descending aorta. Bold arrows indicate the course of the right coronary artery. LPA = Left pulmonary artery; RPA = Right pulmonary artery.
to define visceroatrial situs, and to delineate complex associated be a useful modality for evaluation of ccTGA patients not only
defects. In patients with interruption of the inferior vena cava, as an adjunct to TTE for initial diagnosis, but also for assessment
systemic return from the lower body can be difficult to delineate prior to surgical repair or for serial follow-up of the systemic RV.
by echocardiography, but is well-defined by cMRI. Because If the presence of a cMRI-incompatible pacemaker or prosthetic
echocardiographic evaluation of RV function in ccTGA patients valve precludes assessment by cMRI, computed tomography
is limited by geometric assumptions, cMRI has become the gold (CT) scans can depict anatomy, but cannot yield functional data
standard for RV function and volume assessment. TV morphology in the manner of a cMRI.33,34
can often be clarified through cMRI. Prior to performing
anatomic surgical repair in a ccTGA patient beyond infancy, Exercise and Stress Testing
cMRI can be useful in evaluation of the LV, with delineation
of mass, volume and ejection fraction. Furthermore, if there are Cardiopulmonary exercise testing by treadmill is an important
concerns about the degree of LV dysfunction, perfusion studies adjunct for ccTGA patient evaluation and management. In
with delayed enhancement MRI may be performed to directly those patients able to perform treadmill tests, exercise capacity
investigate scarring of the LV myocardium prior to committing is determined through minute ventilation, carbon dioxide
630 this ventricle to systemic workload. Cardiac MRI may therefore production and oxygen consumption. Impaired exercise
therapy for optimal CHF treatment in patients with systemic 44
RV is lacking. As an adjunct to medical therapy or in cases
where medical therapy has failed, cardiac resynchronization
http://vip.persianss.ir
8 Table 1
Surgical repair and palliation for congenitally corrected transposition of the great arteries: classic and anatomic pathways for ccTGA
with associated defects.
Cyanotic Heart diseases
Classic/Physiologic Pathway
Associated defect Palliation/repair
VSD VSD closure
VSD + PS VSD closure + PS relief
VSD + PS/atresia Biventricular Repair
• VSD closure + LV – PA conduit
VSD + PS/atresia + Univentricular repair
• Straddling AV valves • Systemic to pulmonary artery shunt
• Hypoplastic RV • Bidirectional Glenn
• Unbalanced AVSD • Fontan
Tricuspid regurgitation TV repair or replacement
Anatomic Pathway
Associated defect Palliation/repair
VSD with normal PV • VSD closure
• Senning/Mustard (atrial switch)
• Arterial switch
VSD + PS with normal PV • VSD closure + PS relief
• Atrial + arterial switch
VSD + PS/atresia • Atrial switch + Rastelli procedure
Restrictive or absent VSD + PS Atrial switch + Nikaidoh procedure
Hypoplastic RV or severe RV dysfunction Hemi-Mustard-BDG modified atrial switch
Tricuspid regurgitation Infants and children: PAB for LV training + atrial/arterial switch
AV = Atrioventricular; AVSD = Atrioventricular septal defect; BDG = Bidirectional Glenn; LV = Left ventricle; PA = Pulmonary artery; PAB = Pulmonary
artery band; PS = Pulmonary stenosis; PV = Pulmonary valve; VSD = Ventricular septal defect;
with coronary artery transfer, VSD closure if necessary, standard for age of PAB placement in this setting, it is
and interatrial baffle by Senning or Mustard procedure. apparent that candidacy for LV training with PAB beyond
The Senning and Mustard operations, referred to as an ‘atrial adolescence is questionable. LV dysfunction and failure can
switch,’ serve to direct systemic venous flow to the TV and RV occur immediately or within days or weeks following PAB
and pulmonary venous flow to the MV and LV. By restoring placement if the band is too restrictive. Reports of late LV
the LV and MV to the systemic circulation, the DS operation dysfunction in ccTGA patients who underwent DS operation
offers the opportunity to improve long-term outcome. Before even after successful LV retraining by PAB placement are
committing the LV to the systemic workload, however, various also of concern.56
criteria must be met that afford the LV the greatest likelihood The combination of progressive systemic RV dysfunction
of success. This includes preoperative LV pressure that is 80 and TR has lead to the consideration of a variation in DS
to 100 percent systemic and normal LV wall thickness and operation for patients with LVOTO. Rather than combining
function for a systemic LV.52,53 In the absence of LVOTO, the atrial and arterial switches, the Senning or Mustard atrial
pulmonary hypertension or an unrestrictive VSD, the switch procedure is combined with a Rastelli operation, in
morphologic LV requires training prior to committing it to the which the LV outflow is baffled from the LV through a large
systemic ventricle in the DS. LV training has been performed VSD to the aorta and a conduit is placed from the RV to the
by placement of a pulmonary artery band (PAB) which is PA. This operation is technically challenging and subject to the
then serially tightened until the pressure load for the naïve LV need for conduit replacements as well as possible reoperation
nears systemic pressure. Median banding time for the purpose for interatrial or interventricular baffle obstructions. Specific
of LV retraining has been reported on average to be 13 to to the Senning/Rastelli operation, risk factors associated with
14 months53-55 although can be considerably less in younger death include longer cardiopulmonary bypass and aortic
patients. Morphologic LV reconditioning with PAB in patients cross-clamp times and there is an increased risk of complete
with systemic RV after atrial switch for dextrotransposition heart block and ventricular dysfunction if the existing VSD
of the great arteries (dTGA) has been described by Poirier requires enlargement.57,58 Nevertheless, intermediate results
et al.53 PAB was performed in this population prior to in a small group of ccTGA patients with VSD and LVOTO
anatomic correction or as bridge to transplant, and the success who underwent this form of anatomic repair suggest good
rate of completing adequate LV retraining was significantly biventricular function and mild or no AV valve insufficiency
less in patients beyond 12 years of age (20 percent of patients up to 17 years postoperatively.59 Aortic root translocation
over 12 years completed the protocol, whereas 62 percent in combination with the atrial switch has also been reported
of patients less than 12 years were able to complete the for anatomic repair in patients with LVOTO.60 After atrial
PAB protocol, p = 0.02).53 While there is no well-defined rerouting, the aortic root is harvested, obstruction in the LVOT 633
http://vip.persianss.ir
8 is relieved, LeCompte maneuver of the pulmonary arteries is (median age 1.1 years, range 0–12 years). Eleven of the 14
performed, and the aortic root is reanastomosed to the original patients had an increase in LV pressure of ≥ 2/3 systolic RV
location of the pulmonary artery. A conduit or pericardial pressure with PAB and demonstrated significantly decreased
Cyanotic Heart diseases
patch is then used to reconstruct the RVOT. This variation TR as the LV geometry became more spherical and the
of anatomic repair, commonly referred to as the Nikaidoh interventricular septum shifted toward the RV. Patients who
procedure, may be suitable for patients with restrictive VSD underwent classic ccTGA repair with procedures that reduced
not amenable to the Rastelli operation.61 LV pressure below that of the RV, such as VSD closure with
An additional variation in the DS for patients with severe LV to PA conduit placement, demonstrated significantly
RV dysfunction, hypoplasia of the RV or abnormal right increased TR postoperatively.48
atrial anatomy includes a modified atrial switch termed the
‘hemi-Mustard/bidirectional Glenn,’ which is performed Outcomes: Physiologic vs Anatomic Repair
in combination with either an arterial switch or a Rastelli
procedure. In this operation only the IVC return is baffled to the Alghamdi and associates66 published a meta-analysis of 11
TV. The SVC is reimplanted into the pulmonary artery creating non-randomized studies totalling 124 ccTGA patients and
a cavo-pulmonary Glenn shunt and the SVC portion of the compared in-hospital mortality between physiologic and
RA is oversewn. Midterm outcomes from the hemi-Mustard/ anatomic repair. Patient age at time of repair ranged from 3
Glenn as reported by Malhotra et al.62 are favorable and hold months to 55 years with 41 percent of patients undergoing
several advantages over the traditional Senning or Mustard definitive repair prior to 1995. Thirty patients underwent
atrial switch. The authors report a prolonged lifespan of the RV physiologic repair, 69 underwent Rastelli-type anatomic
to PA conduit due to volume-unloading of the RV, increased repair, and 25 received anatomic repair with the standard
intra-atrial space for pulmonary venous return (and therefore double switch operation. The Rastelli-type anatomic repair
less risk of pulmonary venous obstruction) and less risk for had significantly lower hospital mortality, while operation
arrhythmia with the reduction in intra-atrial suture lines.62 It before 1995 demonstrated an increased mortality risk.66 A
remains to be seen if the hemi-Mustard/bidirectional Glenn large risk analysis performed by Shin’oka et al.58 combined
variant of the DS will prove favorable in long-term studies. ccTGA patients with a group of systemic RV patients with
discordant AV connections, (n = 189) and compared long-
Tricuspid Regurgitation term results of definitive surgical repair with respect to
hospitalization, late mortality and reoperation. Risk factors
Although it is reasonable to medically manage mild TR for hospital death included preoperative moderate TR and
with anticongestive therapy and afterload reduction, surgical intraoperative cardiopulmonary bypass time of over 240
intervention is indicated in cases of moderate or moderate to minutes. The presence of TR was also a risk factor for late
severe TR. TV repair for ccTGA patients is rarely successful, mortality. Risk for reoperation was highest in patients with
and most patients require valve replacement. This can prove preoperative cardiomegaly (cardiothoracic ratio of > 0.6)
problematic in young children because of the relatively large at least a moderate degree of TR, operative need for VSD
prosthesis needed to allow for growth. Palliation with PAB enlargement, and weight less than 10 kg. Although survival of
may therefore be reasonable in infants and young children, patients undergoing classic repair without TR was satisfactory
since it has been shown that severe TV insufficiency in comparison to anatomic repair, patients with ccTGA and
leading to RV dysfunction has the greatest impact on long- discordant AV connections with TR demonstrated improved
term survival.13,48 Several groups have concluded that TV survival with anatomic repair.58 More recently Lim and
replacement should be considered at the earliest sign of colleagues67 report results from a multicenter study including
RV dysfunction and recommend operation before systemic 167 patients who underwent biventricular ccTGA repair. Of
ventricular ejection fraction (EF) decreases below 40 to the patients studied, 123 underwent physiologic repair (ASD
44 percent, as low preoperative systemic EF has been shown or VSD closure, TV surgery and/or pulmonary ventricle to
to correlate with poor outcome.63,64 PA conduit placement), and 44 underwent anatomic repair
As an additional alternative, Metton and associates (atrial + arterial switch or atrial + interventricular rerouting
advocate the use of PAB in asymptomatic ccTGA neonates procedure) over the years 1983 to 2009. Long-term results
and infants with intact ventricular septum to maintain rather of biventricular repair revealed an estimated survival of
than train the LV.65 In Metton’s group the TV was not repaired 83.3 percent ± 0.05 percent at 25 years. The incidence of
at PAB placement, as it was thought that PAB placement complete heart block was lower for the anatomic repair
(with subsequent elevation in LV pressures and alteration of group and there was a late mortality of 5.9 percent after
the septal geometry) may improve TR that was present prior physiologic repair in comparison to 0 percent after anatomic
to banding.54 This mechanism is described by Kral Kollars repair. Freedom from systemic AV valve and ventricular
et al.48 in 14 patients who underwent PAB for LV retraining dysfunction was significantly higher after anatomic repair.
634
The authors concluded that anatomic repair is superior to Conclusion 44
physiologic repair in patients with two adequately sized
ventricles. However high risk groups such as those patients The debate continues over efficacy and long-term follow-up in
http://vip.persianss.ir
8 11. Hoffman JIE. Congenitally Corrected Transposition of 25. Jennings HS, 3rd, Primm RK, Parrish MD, et al. Coronary
the Great Arteries. In: Hoffman JIE (Ed). The Natural and arterial revascularization in an adult with congenitally corrected
Unnatural History of Congenital Heart Disease. Oxford: transposition. Am Heart J. [Case Reports]. 1984;108:598-600.
Cyanotic Heart diseases
Wiley-Blackwell; 2009. pp. 206-17. 26. Orchard EA, Ormerod O, Myerson S, et al. Congenitally corrected
12. Presbitero P, Somerville J, Rabajoli F, et al. Corrected transpo transposition of the great arteries presenting in a nonagenarian.
sition of the great arteries without associated defects in adult Circulation. [Case Reports]. 2010;122:e441-44.
patients: clinical profile and follow-up. Br Heart J. [Multicent 27. Scardi S, Knoll P, Pandullo C. Corrected transposition of
er Study]. 1995;74:57-59. the great vessels and situs inversus viscerum in a 65-year-
13. Prieto LR, Hordof AJ, Secic M, et al. Progressive tricus old oligosymptomatic woman. Circulation. [Case Reports].
pid valve disease in patients with congenitally corrected 1999;100:777.
transposition of the great arteries. Circulation. 1998;98: 28. Beauchesne LM, Warnes CA, Connolly HM, et al. Outcome
997-1005. of the unoperated adult who presents with congenitally
14. Graham TP, Jr Bernard YD, Mellen BG, et al. Long-term out corrected transposition of the great arteries. J Am Coll Cardiol.
come in congenitally corrected transposition of the great ar 2002;40:285-90.
teries: a multi-institutional study. J Am Coll Cardiol. [Com 29. Carey LS, Ruttenberg HD. Roentgenographic Features of
parative Study Multicenter Study Research Support, Non-U.S. Congenital Corrected Transposition of the Great Vessels:
Gov’t]. 2000;36:255-61. A Comparative Study of 33 Cases with a Roentgenographic
15. Hornung TS, Bernard EJ, Celermajer DS, et al. Right Classifiction Based on the Associated Malformations and
ventricular dysfunction in congenitally corrected transposition Hemodynamic States. Am J Roentgenol Radium Ther Nucl
of the great arteries. Am J Cardiol. 1999;84:1116-9, A10. Med. 1964;92:623-51.
16. Hornung TS, Bernard EJ, Jaeggi ET, et al. Myocardial perfusion 30. Warnes CA. Transposition of the great arteries. Circulation.
defects and associated systemic ventricular dysfunction in [Review]. 2006;114:2699-709.
congenitally corrected transposition of the great arteries. Heart. 31. Oechslin E. Physiologically “Corrected” Transposition of the
[Case Reports]. 1998;80:322-26. Great Arteries. In: Lai WW, Mertens LL, Cohen MS, Geva T
17. Fratz S, Hauser M, Bengel FM, et al. Myocardial scars (Eds). Echocardiography in Pediatric and Congenital Heart
determined by delayed-enhancement magnetic resonance Disease: From Fetus to Adult. Oxford: Wiley-Blackwell; 2009.
imaging and positron emission tomography are not common in pp. 439-55.
right ventricles with systemic function in long-term follow-up. 32. Caso P, Ascione L, Lange A, et al. Diagnostic value of
Heart. 2006;92:1673-77. transesophageal echocardiography in the assessment of
18. McEwing RL, Chaoui R. Congenitally corrected transposition congenitally corrected transposition of the great arteries in
of the great arteries: clues for prenatal diagnosis. Ultrasound adult patients. Am Heart J. [Clinical Trial Comparative Study
Obstet Gynecol. [Case Reports]. 2004;23:68-72. Multicenter Study]. 1998;135:43-50.
19. Paladini D, Volpe P, Marasini M, et al. Diagnosis, characteriz 33. Schmidt M, Theissen P, Deutsch HJ, et al. Congenitally corrected
ation and outcome of congenitally corrected transposition of transposition of the great arteries (L-TGA) with situs inversus
the great arteries in the fetus: a multicenter series of 30 cases. totalis in adulthood: findings with magnetic resonance imaging.
Ultrasound Obstet Gynecol. [Multicenter Study]. 2006;27:281- Magn Reson Imaging. [Case Reports]. 2000;18:417-22.
85. 34. Teo LL, Hia CP. Advanced cardiovascular imaging in
20. Shima Y, Nakajima M, Kumasaka S, et al. Prenatal diagnosis congenital heart disease. Int J Clin Pract. 2011;65:17-29.
of isolated congenitally corrected transposition of the great 35. Tay EL, Frogoudaki A, Inuzuka R, et al. Exercise intolerance
arteries. Arch Gynecol Obstet. [Case Reports]. 2009;279:557- in patients with congenitally corrected transposition of the
59. great arteries relates to right ventricular filling pressures. Int J
21. Wan AW, Jevremovic A, Selamet Tierney ES, et al. Comparison Cardiol. [Research Support, Non-U.S. Gov’t]. 2011;147:219-
of impact of prenatal versus postnatal diagnosis of congenitally 23.
corrected transposition of the great arteries. Am J Cardiol. 36. Giardini A, Lovato L, Donti A, et al. Relation between right
[Comparative StudyMulticenter Study]. 2009;104:1276-79. ventricular structural alternans and markers of adverse clinical
22. Zhang Y, Cai A, Sun W, et al. Prenatal diagnosis of fetal outcome in adults with systemic right ventricle and either
congenitally corrected transposition of the great arteries. congenital complete (after Senning operation) or congenitally
Prenat Diagn. 2011;31:529-35. corrected transposition of the great arteries. Am J Cardiol.
23. Friedberg DZ, Nadas AS. Clinical profile of patients with 2006;98:1277-82.
congenital corrected transposition of the great arteries. A study 37. Dodge-Khatami A, Tulevski, II, Bennink GB, et al. Compar
of 60 cases. N Engl J Med. 1970;282:1053-59. able systemic ventricular function in healthy adults and
24. Chang HY, Yin WH, Hsiung MC, et al. A heart reversed patients with unoperated congenitally corrected transposition
triply: situs inversus totalis with congenitally corrected using MRI dobutamine stress testing. Ann Thorac Surg.
transposition of the great arteries in a middle-aged woman. [Comparative Study Research Support, Non-U.S. Gov’t].
Echocardiography. [Case Reports]. 2009;26:617-21. 2002;73:1759-64.
636
38. Fratz S, Hager A, Busch R, et al. Patients after atrial switch 50. Hraska V, Duncan BW, Mayer JE, et al. Long-term outcome of 44
operation for transposition of the great arteries can not increase surgically treated patients with corrected transposition of the
stroke volume under dobutamine stress as opposed to patients great arteries. J Thorac Cardiovasc Surg. [Comparative Study].
http://vip.persianss.ir
8 62. Malhotra SP, Reddy VM, Qiu M, et al. The hemi-Mustard/ 66. Alghamdi AA, McCrindle BW, van Arsdell GS. Physiologic
bidirectional Glenn atrial switch procedure in the double- versus anatomic repair of congenitally corrected transposition of
switch operation for congenitally corrected transposition the great arteries: meta-analysis of individual patient data. Ann
Cyanotic Heart diseases
of the great arteries: rationale and midterm results. J Thorac Thorac Surg. [Comparative Study Meta-Analysis]. 2006;81:
Cardiovasc Surg. 2011;141:162-70. 1529-35.
63. Mongeon FP, Connolly HM, Dearani JA, et al. Congenitally 67. Lim HG, Lee JR, Kim YJ, et al. Outcomes of biventricular repair
corrected transposition of the great arteries ventricular function for congenitally corrected transposition of the great arteries. Ann
at the time of systemic atrioventricular valve replacement Thorac Surg. [Comparative Study]. 2010;89: 159-67.
predicts long-term ventricular function. J Am Coll Cardiol. 68. Connolly HM, Grogan M, Warnes CA. Pregnancy among
[Comparative Study Research Support, Non-U.S. Gov’t]. women with congenitally corrected transposition of great
2011;57:2008-17. arteries. J Am Coll Cardiol. 1999;33:1692-95.
64. Van Son JA, Danielson GK, Huhta JC, et al. Late results of 69. Gelson E, Curry R, Gatzoulis MA, et al. Pregnancy in women
systemic atrioventricular valve replacement in corrected with a systemic right ventricle after surgically and congenitally
transposition. J Thorac Cardiovasc Surg. 1995;109:642-52; corrected transposition of the great arteries. Eur J Obstet
discussion 52-3. Gynecol Reprod Biol. 2011;155:146-49.
65. Metton O, Gaudin R, Ou P, et al. Early prophylactic pulmonary 70. Therrien J, Barnes I, Somerville J. Outcome of pregnancy in
artery banding in isolated congenitally corrected transposition patients with congenitally corrected transposition of the great
of the great arteries. Eur J Cardiothorac Surg. [Evaluation arteries. Am J Cardiol. 1999;84:820-24.
Studies]. 2010;38:728-34.
638
C hapter
45 Common Atrium
common atrium entering ipsilateral sides of the common atrium separate from
the inferior vena cava (IVC) attachment. Anomalies of the
Virtual absence of atrial septum is a rare congenital anomaly, pulmonary venous return occur in nearly all cases of right
which may occur in isolation or as a part of complex isomerism. If the veins return to the atrium, it is usually to
heterotaxy syndromes. It occurs in less than 1 percent of a common collector in the roof of the common atrium. The
all congenital heart diseases (CHDs).1 In 1907, Young and coronary sinus is usually absent in such situations. When there
Robinson described this entity as a part of their series on the is a persistent left superior vena cava (SVC), it drains directly
malformations of human heart.2 into the left upper corner of the common atrium. Also, the
coronary venous blood drains directly into the left side of the
IS IT SAME AS SINGLE ATRIUM? common atrial cavity. This partly explains the mild desaturation
that is commonly encountered in such instances.8,9
The terms common atrium and single atrium have been used
interchangeably in the literature. Some authors suggest that Left Isomerism
single atrium is to be applied to the defects with complete
absence of atrial septum, absence of interventricular Common atrium occurs in almost one-third of left isomerisms.
communication and absence of malformations of the This complex is usually associated with polysplenia, interrupted
atrioventricular (AV) valves, while common atrium is to be IVC (which sometimes pose serious problems in determining
applied to the defects with complete absence of the atrial atrial situs) and anomalous pulmonary venous connection to
septum with malformations of the AV valves.7 both sides of the common atrium. 8,9
These semantic confusions3-5 were sorted out and now
both the terms refer to the complete absence of the interatrial SYNDROMES ASSOCIATED WITH COMMON ATRIUM
septum.6
In this chapter, we will focus on both common atrium Ellis van Creveld syndrome: A strong association between
and single atrium, avoiding detailed overlap with AV single atrium and postaxial hexadactyly (Figures 1A and B)
malformations and heterotaxy syndromes, which are dealt has been reported10 and indicates a diagnosis of Ellis van
separately in Chapter 20 and 10 respectively. Creveld syndrome.
Ivemark syndrome consists of intracardiac anomalies,
COMMON ATRIUM AND ISOMERISMS abnormal lobation of the lungs and abdominal heterotaxy.11
In an interesting observation, Spencer and colleagues
The complex heterotaxy syndromes are usually associated reported common atrium in two pairs of conjoint twins.12
with common atrium.
CLINICAL MANIFESTATIONS
Right Isomerism
Here, we shall concentrate on the single atrium without
There is an almost 50 percent incidence of common atrium associated lesions. In common atrium with complex lesions,
in right isomerisms. This complex is usually associated with the symptoms and findings of coexisting complex lesions
asplenia, midline liver with both right and left hepatic veins supersede that of the atrial component.
http://vip.persianss.ir
8
Cyanotic Heart diseases
A B
Figures 1A and B: Ellis-Van Creveld syndrome: A. Postaxial hexadactyly of the hands with hypoplastic nails; B. Peg teeth and malocclusion
When the entire atrial septum is virtually absent, there is murmur. This will add to the overall volume load on heart.
a mandatory admixture of blood received from systemic and
pulmonary circulations into the atrial cavity. This explains the INVESTIGATIONS
mild desaturaion that can be noticed. However, in the setting
of right isomerism, the degree of desaturation may be higher After a meticulous clinical examination, one should proceed
for reasons explained earlier. to the basic battery of investigations, which would add to the
Symptoms of high pulmonary blood flow predominate diagnosis and management decisions.
in infancy. As in any non-restrictive atrial septal defect, the
compliance of the corresponding ventricles will determine the Electrocardiography
direction and magnitude of the flow out of the single atrial
cavity. The presenting features include dyspnea on exertion, The 12-lead electrocardiography (ECG) shows same pattern
fast breathing, failure to thrive, suck-rest-suck cycles and as partial AV canal defect or a primum ASD. Rhythm is
excessive sweating. As a general rule, the symptoms occur usually sinus, but in the setting of an abnormal situs, one may
earlier and progress faster than isolated atrial septal defects come across various degrees of conduction blocks including
(ASD) or primum defects. When the pulmonary vascular complete heart block. The P waves in lead II, III and AVF can
resistance is normal, precordium appears active. Apical be both tall and broad. Prolongation of PR interval is noted
impulse would be prominent and of right ventricular type. in upto two-thirds. This is a manifestation of increased intra-
Second heart sound would reveal a wide split and no change atrial conduction time.13 The mean QRS axis may show left
with respiratory cycle. The extent of pulmonary hypertension axis or superior axis, ranging from minus 30 degrees to minus
would determine the loudness of the pulmonary component 120 degrees. The QRS can be notched in the inferior leads
of second heart sound. Precordial auscultation would reveal and a typical rsR’ pattern is observed in V1. QRS pattern may
an ejection systolic murmur with its typical crescendo- suggest volume overload of right ventricle. However, with
decrescendo quality at the left upper sternal border. The same advancing age, it may also show pressure overload pattern due
murmur can be appreciated at the back and sometimes in the to increasing pulmonary vascular resistance. In the presence
axillae. One can also appreciate a mid-diastolic murmur in of normal pulmonary vascular resistance and right ventricular
left lower sternal border. This murmur has a soft-quality and function, even a significant MR is unlikely to show a left
is often described as ‘absence of silence’. The mid-diastolic ventricular volume overload pattern in the ECG (Figure 2).
murmur is due to the increased blood flow across the tricuspid
valve when the pulmonary vascular resistance and the right Chest Radiograph
ventricular functions are normal. Not infrequently, common
atrium is associated with an abnormal mitral valve. Clefts A well taken chest radiograph in posteroanterior projection is
in the mitral valve leaflets are common in such settings. The an invaluable tool in management decisions. Cardiomegaly is
640 resultant mitral regurgitation (MR) can produce a pansystolic evident. Right atrial enlargement and right ventricular apex
45
Common Atrium
Figure 2: Electrocardiography of a patient with common atrium shows left axis deviation, rsR' in V1, notched QRS in inferior leads
Figure 3: Chest X-ray in posterioanterior view shows cardiomegaly Figure 4: Echocardiography in four-chamber view showing complete
with dilatation of right atrium and right ventricle absence of the interatrial septum in 8 years old girl with common
atrium (CA) with both atrioventricular valves (arrow) at the same level,
with a mid-muscular ventricular septal defect. LV = Left ventricle;
RV = Right ventricle.
are usual, even in the presence of significant MR. Pulmonary abnormal patterns of pulmonary and systemic veins. Apical
vascularity pattern may help in deciding the operability. four chamber is diagnostic (Figure 4).
Plethoric lung fields suggest clear operability, whereas If the IVC is uninterrupted, a long, redundant eustachian
oligemic lung fields are against it. However, one should not valve tissue might be seen wandering in the common atrial
confuse pulmonary venous congestion with plethoric lung cavity. It should not be confused with residual septal tissue.
fields (Figure 3). Apical four-chamber view is useful in assessing the
ventricular cavities and the av valves. When one of the
Echocardiography ventricles looks unusually small, measuring the annuli of AV
valves and comparing them against the Z-score charts would
Subcostal imaging is best suited to make an accurate diagnosis. be useful in deciding feasibility of two-pump repair. The view
Both coronal and sagital planes help in delineating the absence also provides good 2D assessment of AV valve morphology. 641
of interatrial septum and also in establishing the normal and Color-Doppler assessment of the AV valves will help in
http://vip.persianss.ir
8
quantifying the regurgitation and the direction of jet, details pulmonary vascular pressures, the right ventricular compliance
of which are very useful in planning a surgical strategy. Color- is much superior to that of left ventricle. In consequence, the
Cyanotic Heart diseases
Doppler of the pulmonary veins with scales set to optimal pulmonary blood flow (Qp) is higher than systemic (Qs). The
Nyquist limit will help in quantifying the venous return, ratio would reduce in the same proportion as pulmonary to
which is an indirect marker of operability. systemic vascular resistance increases. With advancing age,
Every echocardiographic examination should also encompass the likelihood of operability comes down.
all the other views to rule out any other coexisting anomaly. It is
not uncommon to find cases in which a coexisting large ductus Cardiac Computed Tomography and Magnetic
or aortopulmonary window was missed. Hence, even after Resonance Imaging
establishing the diagnosis from subcostal and apical views, it is
still important to do a meticulous evaluation via parasternal and Cardiac computed tomography (CT) evaluation with contrast
suprasternal windows to determine the presence and absence of study is useful in delineating the systemic and pulmonary
coexisting anomalies. venous courses. However, CT cannot delineate the intracardiac
Role of 3D echocardiography: The utility of 3D- defect, nor can it assess the volumetrics. However, MRI of
transthoracic and 3D-transesophageal echocardiography heart can provide data that 2D-echocardiography cannot. MRI
(TEE) are well established in the evaluation of atrial septal can indicate the lack of atrial septum, amount of shunting, size
defects, especially in deciding the utility of transcatheter and function of both ventricles, along with anatomical details
device closures. However, the same cannot be extrapolated of pulmonary and systemic veins and coexisting lesions.15
for single atrium. With some effort, additional information With all these faculties up its sleeve, MRI may serve as the
can be obtained regarding the venous drainages. With primary imaging modality in the future.
advanced software, volumetrics can be assessed using 3D
echocardiography enabling the shunt calculations. TREATMENT
Cardiac Catheterization and Angiography Once the diagnosis is confirmed, the objective is to get the
anatomical repair early, preferably by 6 to 12 months of life.
Development of pulmonary vascular obstructive disease It is pertinent to make use of any modality of investigation
in single atrium is much faster than that in isolated which helps surgical decision making. An asymptomatic child
secundum ASD or partial AV canal defect of primum with normal pulmonary artery pressures need not be given any
variant. Whether development of early pulmonary medication other than watchful observation. Judicious use of
vascular disease in some common atrium patients is due diuretics and angiotensin converting enzyme inhibitors can
to a genetic predisposition (related to coexisting abnormal be advocated in symptomatic children, more so if av valve
substrate in the lung or congenital abnormalities in the regurgitation is an issue. Digoxin is best avoided, especially
pulmonary arterial vasculature) or an association with when the status of the sinus node is unclear.16 For those
idiopathic pulmonary hypertension is unknown. Due to with postoperative pulmonary artery hypertension, targeted
the rarity of condition and the eventual paucity of data therapy for pulmonary hypertension may be beneficial.14 The
on the natural history of common atrium and pulmonary surgical results are termed ‘good’ to ‘excellent’ by most of the
vascular disease, determining which patients with common authors.17,18 Even advanced age is not a contraindication to
atrium will develop early pulmonary vascular obstructive operation.19
disease remains challenging.14 Hence, the threshold for Splenic status is an important determinant of outcome. In
operability testing is low in many centers. However, with asplenia or reduced splenic function, use of irradiated blood,
advent of better echocardiographic techniques and non- special precautions to ensure sepsis free handling, dedicated
invasive volumetrics assessment by magnetic resonance staffing, judicious isolation and limitation of visitors in the
imaging (MRI) and 3D echocardiography the need for perioperative period would add to the success of the procedure.
catheterization studies has significantly come down. Since Common atrium can present technical challenges to the
the developing countries may still see many unevaluated surgeon, even when the anatomical details are well delineated.
and untreated grown-up CHD patients, catheterization It should be remembered that the surgeon is not just closing
studies may become essential to get the correct picture. an ASD here, but is actually reconstructing the entire atrial
The mixing of pulmonary and systemic venous returns septum. The most common material used to achieve this
is near complete due to lack of any interface between them. is pericardium. This patch is usually diverted leftward to
However, the relative flow of this mixture via AV valves incorporate the left SVC orifice on the right side of the
depends on the individual compliances of corresponding patch. Issues like absence of coronary sinus take away the
ventricles, which is determined by the vascular resistances landmark of conduction system for the surgeon on the table.
642 of the distal vascular beds. Hence, in the presence of low This compels the surgeon to take the sutures on the tricuspid
45
valve posteriorly to be carried on to right atrial wall beyond 4. Rastelli GC, Rahimtoola SH, Ongley PA, et al. Common
the tricuspid annulus. Some surgeons have used the base of atrium: anatomy, hemodynamics, and surgery. J Thorac
Common Atrium
the mitral valve to anchor sutures.20 Cardiovasc Surg. 1968;55:834-41.
A well reconstructed interatrial septum does very well 5. Gerbode F. Endocardial cushion defects. In: Wu YK, Peters
RM (Eds). International Practice in Cardiothoracic Surgery.
in the postoperative period.17 The decision to continue
Beijing: Science Press; 1985. p. 751.
medications would depend upon the postoperative normaliz
6. Behrendt DM. Atrial septal defect. In: Mavroudis C, Backer
ation of hemodynamics. However, it should be noted that CL (Eds). Pediatric cardiac surgery, 2nd edition. St Louis;
all children with altered splenic function should receive Mosby, 1994. pp. 193-200.
life-long prophylaxis and vaccination against encapsulated 7. Levy MJ, Salomon J, Vidne BA. Correction of single and
bacteria and preferably, annual influenza vaccine. This should common atrium, with reference to simplified terminology.
be emphasized to parents at the time of discharge and re- Chest. 1974;66:444-46.
emphasized during follow up visits. It is useful to get all this 8. Anderson RH,Webb S, Brown NA. Defective lateralisation in
practical information on patient care printed on a handy card children with congenitally malformed hearts. Cardiol Young.
1998;8:512-31.
and issued to the parents for their reference.
9. Van Praagh S, Santini F, Sanders SP. Cardiac malpositions
with special emphasis on visceral heterotaxy (asplenia and
Conclusion polysplenia syndromes). In: Fyler DC (Ed). Nadas’ pediatric
cardiology. Philadelphia’ Hanley and Belfus; 1992. pp. 589-608.
Common atrium and single atrium are two different 10. Digilio MC, Marino B, Giannotti A, et al. Single atrium,
terminologies and there should not be any nosological atrioventricular canal/postaxial hexadactyly indicating Ellis
confusion. Common atrium is a part of complex coexisting van Creveld syndrome. Hum Genet. 1995;96:251-53.
anomalies, whereas single atrium is isolated. Syndromic 11. Gutgesell HP. Cardiac malposition and heterotaxy. In: Garson
associations are well known. Presentation is similar to that of A, Bricker JT, Fisher DJ, Neish SR (Eds). The science and
practice of pediatric cardiology. 2nd edition. Baltimore:
ASD, albeit earlier and with evidence of cyanosis. Evaluation
Williams and Wilkins; 1998. pp. 1539-61.
should consist of a careful search for coexisting anomalies,
12. Spencer R, Robichaux WH, Superneau DW, et al. Unusual
especially of the pulmonary, systemic venous drainage and cardiac malformations in conjoint twins. Pediatr Cardiol.
the AV valves. Early surgical correction around 1 year of age 2002;23:631-38.
is recommended. Surgical results are good and age should not 13. Fournier A, Young ML, Garcia OL, et al. Electrophysiologic
be a deterrent as long as the patient is operable. cardiac function before and after surgery in children with
atrioventricular canal. Am J Cardiol. 1986;57:1137-41.
14. Ferdman DJ, Brady D, Rosenzweig EB. Common atrium and
“Wherever the art of medicine is loved, pulmonary vascular disease. Pediatr Cardiol 2011;32:595-98.
15. Piaw CS, Kiam OT, Rapaee A, et al. Use of non-invasive phase
there is also a love of humanity”
contrast magnetic resonance imaging for estimation of atrial septal
—Hippocrates
defect size and morphology: a comparison with transesophageal
echo. Cardiovasc Intervent Radiol. 2006;29:230-34.
16. Wu MH, Wang JK, Lin JL, et al. Cardiac rhythm disturbances in
Acknowledgment patients with left atrial isomerism. Pacing Clin Electrophysiol.
2001;24:1631-38.
We wish to thank Dr IB Vijayalakshmi, Professor of Pediatric 17. Murphy JG, Gersh BJ, McGoon MD, et al. Long-term outcome
Cardiology, for providing all the images. after surgical repair of isolated atrial septal defect. Follow-up
at 27 to 32 years. N Engl J Med. 1990;323:1645-50.
18. Roos-Hesselink JW, Meijboom FJ, Spitaels SE, et al. Excellent
References survival and low incidence of arrhythmias, stroke and heart failure
long-term after surgical ASD closure at young age. A prospective
1. Campbell M. Incidence of cardiac malformations at birth and
follow-up study of 21–33 years. Eur Heart J. 2003;24:190-97.
later and neonatal mortality. Br Heart J. 1973;35:189-200.
19. Inoue T, Kawamura J, Takeda M, et al. An elder case of
2. Young AH, Robinson A. Some malformations of the human
common atrium: surgical repair in a 56-year-old man [in
heart. M Chron. 1907/1908;47:96.
Japanese]. Kyobu Geka. 1991;44:793-96.
3. Campbell M, Nissen GAK. Endocardial cushion defects,
20. Pan-Chih, Chen-Chun. Surgical treatment of atrioventricular
common atrioventricular canal and ostium primum. Br Heart
canal malformations. Ann Thorac Surg. 1987;43:150-54.
J. 1957;19:403.
643
http://vip.persianss.ir
C hapter
46 Single Ventricle
Single Ventricle
two ventricular masses. They proposed these hearts should
be classified on the basis of the embryological development
and continued to use the term ‘double inlet left ventricle’ and
‘Tricuspid Atresia’.
In 1984, Anderson11 et al responded by introducing the
term ‘univentricular atrioventricular connection’ to
describe hearts in which both inlets (whether patent or not)
are primarily committed to one dominant ventricle.
Thus, according to Van Praagh, a single or common
ventricle is one ventricular chamber that receives both the
Figure 2: The figure shows a morphological RV, which is tripartite: an tricuspid and mitral valves or a common atrioventricular
inlet, apical trabecular and outlet portions. The apical trabeculations valve. So, this definition excludes tricuspid and mitral atresia.
are coarse. The solid red line indicates the atrioventricular junction,
Anderson’s system likewise emphasizes the nature of the
while the dotted red line indicates the ventriculoarterial junction.
Courtesy: Reprinted with permission from reference 16 connections between the atrial and ventricular structures,
asserting that the unifying criterion for univentricular hearts is
that the entire atrioventricular junction is connected to only one
chamber in the ventricular mass. A second ventricular chamber,
if present, will lack any atrioventricular connection and hence
be rudimentary. This system makes the distinction between
hearts with a double inlet ventricle versus hearts with absence
of an atrioventricular connection, but acknowledges that
because a heart with absence of one atrioventricular connection
is also a univentricular heart, then tricuspid atresia is among
those anomalies associated with a univentricular heart.
The final consensus of the STS-Congenital Heart Surgery
Database Committee12 and the European Association
for Cardiothoracic Surgery was that the nomenclature
proposal for single ventricle hearts would encompass
Figure 3: The figure shows a morphological LV, which is also tripartite.
hearts with double inlet atrioventricular connection,
In contrast to Figure 2, the apical trabeculations are smooth. The solid both double inlet left ventricle (DILV) and double inlet
red line indicates the atrioventricular junction, while the dotted red right ventricle (DIRV), hearts with absence of one
line indicates the ventriculoarterial junction. Courtesy: Reprinted with atrioventricular connection (mitral atresia and tricuspid
permission from reference 16
atresia), hearts with a common atrioventricular valve and
only one completely well-developed ventricle (unbalanced
common atrioventricular canal defect), hearts with
only one fully well-developed ventricle and heterotaxia
syndrome (single ventricle heterotaxia syndrome) and
finally other rare forms of univentricular hearts that do
not fit in one of the specified major categories. Despite the
recognition that hypoplastic left heart syndrome (HLHS)
is a common form of univentricular heart, with a single
or dominant ventricle of right ventricular morphology,
the current nomenclature and database proposal includes
it in an entirely separate section. Also, it is recognized
that a considerable variety of other structural cardiac
malformations such as pulmonary atresia with intact
ventricular septum, biventricular hearts with straddling
atrioventricular valves and some complex forms of
Figure 4: The left hand panel shows a double inlet and double double outlet right ventricle (DORV), may at times be
outlet from morphological left ventricle (LV), which is the functional best managed in a fashion similar to that which is used to
single ventricle. The right hand panel demonstrates the presence of
treat univentricular hearts. However, we are not going to 645
a rudimentary right ventricle (RV), identified from its coarse apical
trabeculations. Courtesy: Reprinted with permission from reference 16 discuss the latter group or HLHS in this chapter.
http://vip.persianss.ir
8 With this short history, we recommend the readers to follow
their own preferred school of morphology. We have tried
to follow Professor Anderson’s method of describing these
cyanotic Heart diSeaSeS
defInItIon
As per the congenital heart surgery nomenclature and
database project,12 single ventricle anomalies are defined as
a heterogeneous group of cardiac malformations that have in
common the feature that only one of the chambers within the
ventricular mass is capable of supporting independently and/
or in combination the systemic and/or pulmonary circulations.
This excludes those cardiac anomalies where even in the
presence of two well-developed ventricles, the heart may be
considered as non septable like a very large ventricular septal Figure 5: This long axis section of a heart with double inlet left ventricle
defect (VSD) where treatment strategy is similar to that of (DILV) shows the relative position of the rudimentary right ventricle and
ventricular septum with respect to inlets. The incomplete RV is located
univentricular hearts. superior to dominant LV. The two inlet valves (yellow arrows) leading
to LV are posteroinferior to the ventricular septum (star). Courtesy:
anatomICal deSCrIptIon of unIVentrICular Reprinted with permission from reference 16
heartS
Morphologically, the univentricular hearts can be broadly
classified into two categories:
I. True Univentricular Heart.
II. Hearts with One Big and Another Rudimentary
Ventricle.
Single Ventricle
Additionally, each class of univentricular heart may have including DILV, single inlet, common inlet and complex single
associated abnormalities of atriovisceral situs, of one or both ventricle heterotaxy syndromes are thought to be polygenic in
atrioventricular valves, of one or both semilunar valves and nature, with recurrence and transmission risks far below that
of the relations (transposition or malposition) of the great expected from Mendelian inheritance. The risk to siblings and
arteries. All these have been diagrammatically summarized in offspring of affected individuals is generally in the order of 2
the Figure 7. to 5 percent.
Figure 7: Schematic representation to show the possible segmental combinations that can result in a functionally univentricular heart.
Courtesy: Reprinted with permission from reference 15. Dom. LV = Dominant left ventricle; Dom. RV = Dominant right ventricle; UV =
Univentricular
647
http://vip.persianss.ir
8
cyanotic Heart diSeaSeS
and sudden unexplained death. Ammash and Warnes reviewed become critical as the ductus closes. In patients with mild
their experience with 13 unoperated adults with univentricular to moderate pulmonary stenosis, they present like tetralogy
hearts to determine, which characteristics permitted long-term of Fallot. They may be relatively asymptomatic,with mild
survival. 11 patients had DILV with transposed great arteries, to moderate cyanosis, clubbing and attain adulthood with
1 patient had DILV with normally related great arteries and 1 retarded growth.
patient had tricuspid atresia. The oldest patient was 66 years
old. All had either moderate-to-severe pulmonary stenosis or The LV type of single ventricle patients have a LV type
pulmonary hypertension. The left ventricular ejection fraction of apical impulse. It can be hyperdynamic in patients with
was normal (n = 11) or mildly depressed (n = 2) and no patient increased PBF. There can be a visible, palpable impulse
had more than mild atrioventricular valve regurgitation. in the third left intercostal space (due to inverted outlet
Twelve patients reported good functional capacity and worked chamber). The second heart sound is loud and palpable
full- or part-time. Thus, despite the overall grim prognosis in (anterior aorta). The systolic thrill at left sternal border is
unoperated patients, some adults with DILV, transposition of indicative of subaortic stenosis. The single ventricle of RV
the great arteries and well-balanced circulations may survive type have a subxiphoid RV impulse. There is no impulse in
into their seventh decade with acceptable functional capacity the third left intercostal space as there is no underlying outlet
and preserved ventricular function. chamber.
Single Ventricle
type of univentricular heart a. Double inlet.
b. Absence of an atrioventricular connection.
As we have discussed before, the univentricular hearts c. Straddling atrioventricular valves.
can be of LV dominance, RV dominance or primitive/
Indeterminate morphology. The best view having to evaluate Double Inlet Connections
this is parasternal short-axis view. The Table 1 and Figure 9
summarizes the findings. The most common univentricular hearts have double inlet
connection, which is usually due to both atrioventricular
Ventriculoarterial Connections valves draining into a common ventricular chamber (88%)
or rarely by a common atrioventricular valve (12%). Usually
The different connections possible are concordant, common atrioventricular valve is associated with heterotaxy
discordant, double outlet from main or outlet chamber and syndromes (asplenia or polysplenia).
single outlet. However, certain combinations are seen more The double inlet is best visualized in short axis and four
frequently. chamber echocardiographic views (Figure 10). In DILV, there
For example, nearly 86 percent of univentricular hearts with is no intervening inlet septum between the right and left
LV dominance30 have discordant ventriculoarterial connections. atrioventricular valves; therefore these valves may actually touch
We have to carefully exclude outflow tract obstruction of the one another when they open in diastole (kissing atrioventricular
great artery arising from the outlet or rudimentary chamber. valves) and both valves are in continuity with posterior great artery.
Only 14 percent of DILV hearts have normally related great
arteries called ‘Holmes heart’. Absence of an Atrioventricular Connection9
In univentricular hearts of RV dominance, the common
pattern is DORV from main chamber or single outlet with Either the right or left atrioventricular connection is absent. In
pulmonary atresia.9 absent connection, the floor of the atrium is entirely muscular
table 1
Echocardiographic diagnosis of univentricular hearts
LV dominance Anterior with either D/L loop Anterior Posterior to trabecular septum
649
Figure 9: Guide for echocardiographic diagnosis of univentricular hearts
http://vip.persianss.ir
8
cyanotic Heart diSeaSeS
Figure 10: An apical four-chamber echocardiographic view of double Figure 11: An echocardiogram in apical four-chamber view showing
inlet left ventricle (LV) showing both mitral and tricuspid valves atretic tricuspid valve (*), concordant left atrioventricular connection
draining into morphological LV which is dominant. The star (*) shows and mild mitral regurgitation. Left ventricle (LV) is dominant
the location of the interventricular communication between dominant
LV and rudimentary right ventricle (RV)
Single Ventricle
Matitiau32 et al reported a method to calculate the area of ventricle anatomy involves a combination strategy based
bulboventricular foramen. Since the foramen is almost never upon palliative and physiologically corrective procedures
circular in shape, its diameter was measured in two orthogonal (Figure 15).
planes (short- and long-axis views: diameter 1 and diameter Palliative procedures are those which correct the imbalance
2 respectively) and then the area was calculated from this between pulmonary and systemic blood flows, without
formula: separating the two circulations. Physiologically, corrective
procedures are those that completely separates the pulmonary
π × diameter 1 × diameter 2 and systemic circulations (creating in series circulations),
Area =
4 thus achieving the goal of unloading the systemic ventricle
and maintaining near normal systemic arterial saturation.
When the area of the bulboventricular foramen is greater
than 2 cm2/m2 BSA, the foramen is always considered as non- hemodynamICS of SInGle VentrICle
restrictive. In patients with area lesser than 1 cm2/m2 BSA, and fontan CIrCuIt33
during the initial palliation, the restrictive bulboventricular
foramen may need to be enlarged. In patients with area of A normal postnatal cardiovascular system consists of a
bulboventricular foramen between 1 to 2 cm2/m2 BSA, a double—pulmonary and systemic—circuit, connected in
guarded waiting policy is justified. In patients, in whom the series, powered by a double pump—the ‘right’ and ‘left’ heart.
bulboventricular foramen is anatomically smaller though non- However, in a univentricular heart, the single ventricle
restrictive by Doppler recordings, a close echocardiographic has to maintain both the systemic and pulmonary blood
watch is justified. circulations, which are not connected in series but in parallel.
There are two main disadvantages: 1. arterial desaturation and
Assessment of the Systemic Veins 2. chronic volume overload to the single ventricle. Such a
chronic volume overload has significant effects on the single
In every patient with univentricular circulation, it is ventricle namely:
mandatory to be precise about the systemic and pulmonary • Dilatation of atrium and ventricle
venous anatomy before planning the surgery. Systemic venous • Eccentric hypertrophy
anomalies commonly present as bilateral superior vena cava • Spherical remodeling with reorientation of wall fibers
or as interrupted inferior vena cava (IVC) as in left isomerism. • Annular dilatation causing progressive atrioventricular
valve regurgitation.
Assessment of the Pulmonary Veins Thus, the hemodynamic problems in univentricular hearts
arise from:
Anomalies of pulmonary venous return are also common • Inherent mechanics of a single ventricle (lack of
anomalies in single ventricular patients, especially in the interventricular coupling and volume overload to single
setting of heterotaxy syndromes. These anomalies have ventricle)
serious repercussions on the outcomes of Glenn shunt • Mechanics of morphological RV versus morphological LV
and extracardiac Fontan surgeries. In single ventricular • Morphology and functional state of atrioventricular valves
physiology with reduced PBF, the anomalous pulmonary • Degree of mixing within single ventricle
venous drainage may not show florid signs since the • Pulmonary vascular resistance (PVR)
pulmonary venous drainage will also be proportionately • Presence and degree of pulmonic or subaortic stenosis
low. The echocardiographer should make serious attempts In 1971, Francis Fontan’ from Bordeaux, France,
to trace all the pulmonary veins meticulously and ensure reported a new approach to the operative correction of these
that no individual pulmonary vein drains anomalously into a malformations. In a ‘Fontan circulation’, the systemic
chamber other than the atria. In case of confusion, one should venous return is connected to the pulmonary arteries without
not hesitate to obtain an angiogram to confirm the pulmonary an interposing ventricle and all shunts at venous, atrial,
venous pathway. ventricular and arterial levels are interrupted. In such a circuit,
To summarize, the check list while doing an echocardiogram the postcapillary energy is no longer ‘wasted’ into the systemic
of univentricular heart is represented in the following veins, but collected and used to push the blood through the lungs.
schematic diagram given in Figure 14. Advantages of a ‘Fontan circuit’ are (near) normalization
651
http://vip.persianss.ir
8
cyanotic Heart diSeaSeS
Figure 14: Schematic diagram showing the checklist while doing an echocardiogram
of univentricular heart. CHF = Congestive heart failure.
of the arterial saturation and adjustment of chronic volume and Baudet in 1971. It diverted the systemic venous return to the
overload at the cost of chronic systemic venous hypertension pulmonary artery (PA) and included the insertion of an aortic or
and congestion. The cardiac ouput is decreased as compared to pulmonary homograft valve, at both the inflow and outflow of
normal subjects, both at rest and during exercise. Typically, the the right ventricle. Some time later, Kreutzer35 and colleagues
cardiac output is no longer determined by the heart, but rather described in a simple way the use of pulmonary valve at the
by transpulmonary flow (itself regulated by PVR). Thus, the connection of the right atrium to the PA. These operations
circuit runs on ‘autopilot’, with little interference possible by collectively called as Atriopulmonary plexy were based on
the clinician. Cardiac output can be increased by improving the principle that the right atrium can act as the pump for the
flow to and into the lungs or by bypassing the lungs with a pulmonary circulation. This concept was later questioned.
fenestration. The effect of pulmonary vasodilators is usually In 1987, de Leval36 et al proposed a major variation that
very modest (Figures 16A to C). consisted of an end-to-side direct anastomosis of the superior
vena cava to the undivided right PA and using a conduit that
Is every fontan Circuit alike? is created inside the atrium, the IVC is also drained to the
652 PA: Lateral Tunnel Technique. In the majority of cases,
The Fontan operation (Figures 17A to C) was first used in 1968 the lateral tunnel is created by insertion of a semicylindrical
for the repair of tricuspid atresia and was described by Fontan34 polytetrafluorethylene (PTFE) baffle incorporating a small
46
Single Ventricle
Figure 15: Surgical management of single ventricle
portion of the lateral atrial wall. In some patients, the extracardiac conduit–inferior vena cava transition. Usually a
lateral tunnel can be created by autologous material from slightly oversized conduit is required in younger children to
the interatrial septum. Its advantages are decreased risk of allow for vessel growth in relation to somatic growth. Our
thrombosis, decreased blood stasis and exposure of a limited institutional protocol is to perform it at a minimum age of
portion of right atrium to the high venous pressures, thus around 3 years and weight of about 15 kg.
reducing the risk of arrhythmias. In addition, the coronary The latter two procedures namely Lateral Tunnel
sinus remains in the low-pressure atrium allowing unimpeded technique and Extracardiac conduits are named as Total
myocardial venous drainage. Cavopulmonary Connection (TCPC). TCPC surgeries offer
Marcellati 37 in 1990 popularized the use of an extracardiac laminar blood flows and are hydraulically more efficient than
interposition graft between the transected IVC and PA: older versions.
Extracardiac Fontan. It allows for better preservation In patients with infrahepatic interruption of the IVC (as
of ventricular and pulmonary function because it requires in left isomerism), only the hepatic veins drain into the right
minimal or no cardiopulmonary bypass. In addition, it avoids atrium. Blood from the lower body reaches the superior caval
right atrial incisions and extensive atrial suture lines. This vein via the azygos vein. In these patients, a bidirectional
reduces the risk of injury to the sinus node and the incidence cavopulmonary anastomosis (Kawashima operation)38 will
of postoperative arrhythmias. However, since the extracardiac result in an almost complete Fontan palliation, redirecting
tunnel is created either by homograft or conduit, it has no blood from the superior vena cava as well as from the azygos
growth potential and is at risk for obstruction by thrombus vein to the pulmonary arteries and leaving only the hepatic
formation or neointimal hyperplasia. The usual size of veins draining into the systemic circulation (Figures 18 653
conduit used is 18 mm and above. This is to allow a uniform and 19).
http://vip.persianss.ir
8
cyanotic Heart diSeaSeS
a
B
B
c
Figures 17a to c: Variations of Fontan surgery. A. The modified classic
Fontan; B. The intracardiac lateral tunnel Fontan; C. The extracardiac
Fontan. In (A), the modified Blalock-Taussig shunt, shown in white, was
taken down and oversewn. In (C), permanent atrial epicardial pacemaker
leads are illustrated in gray. Courtesy: Reprinted from reference 51
Single Ventricle
Figure 18: This subcostal sagittal echocardiographic view shows Figure 20: This suprasternal echocardiogram in a post Glenn child
interrupted IVC with azygos continuation (Az) posterior to descending shows the laminar flow in Glenn shunt (SVC connected to RPA with
aorta (D Ao) arrow depicting the site of anastomosis). RPA = Right pulmonary
artery; SVC = Superior vena cava.
http://vip.persianss.ir
8 than 85 percent and lesser than 75 percent signify increased
and decreased PBF, respectively.
The two most important cath data required by surgeon
cyanotic Heart diSeaSeS
Single Ventricle
– Existence of surgically created communication (fenes-
tration)
– Development of collateral arteriovenous circulation
(systemic and pulmonary)
• Decreased exercise tolerance
• Cognitive disorders
• Protein-losing enteropathy (PLE)
• Progressive liver failure
• Plastic bronchitis.
Mair et al48 studied the preoperative risk factors contributing
to long-term complications and reported them as:
• The age of the patient before surgery
• Existence of previous palliative surgical procedures
• The anatomy of the complex congenital disease
• Heterotaxy syndromes
• Elevated PA pressure before surgery
Figure 24: This schematic diagram depicts a lateral tunnel procedure
• Significant regurgitation of the atrioventricular connection
with fenestration (arrow). Ao = Aorta; LT = Lateral tunnel; LPA = Left
pulmonary artery; RPA = Right pulmonary artery; SVC = Superior vena • NYHA class III/IV before surgery.
cava.
Complications post-fontan operation
the Fontan circulation. Functional Status and Exercise Tolerance49
In a subgroup of patients at increased risk (young
age at operation, increased mean PA pressure and PVR, More than 90 percent of all hospital survivors are in NYHA
raised ventricular end-diastolic pressures and significant functional class I/II. Most patients do well educationally and
atrioventricular valve regurgitation) a small fenestration can can pursue a variety of professional careers. However, with
be created in the intra-atrial tunnel at the time of TCPC to time there is a progressive decline of functional status in some
allow a protective right-to-left shunt (Figure 24). The potential subgroups.
benefits are a lower central venous pressure and better single
ventricle preload, albeit at the expense of a right-to-left shunt Ventricular Function33
and mild cyanosis. These benefits were found to be greatest in
the immediate postoperative period when, as a consequence All studies reported the ventricle of a functionally univentricular
of cardiopulmonary bypass and myocardial ischemia, heart to be dilated, hypertrophic and hypocontractile. It can be
myocardial function was impaired and elevated PVR was a caused by the congenital malformation itself, previous surgical
problem. This modification has improved operative survival interventions or the very abnormal working conditions of the
rates among high risk patients and shortened duration of ventricle at various stages of palliation, both before and after
pleural effusions and length of hospital stay.46 A considerable Fontan.
percentage of small fenestrations will close spontaneously During the first month after birth, the ventricle is always
later on. In patients with persistently patent fenestration and volume overloaded. This leads to dilatation and spherical
mild cyanosis it remains controversial whether interventional configuration, cardiac overgrowth and eccentric hypertrophy.
occlusion is required later. In patients with increasing By performing Fontan operation, the preload is reduced to
cyanosis during exercise, transcatheter device occlusion of levels well below normal for BSA (50–70%) and even more
fenestration is recommended in the presence of appropriate when expressed in relation to ventricular size (25–70%). The
hemodynamics.47 It should not be done in patients with ventricle thus undergoes a transition from volume overloaded
preoperative risk factors, residual PA distortion or anastomotic and overstretched, to overgrown and severely underloaded.
stenosis, significant atrioventricular regurgitation and signs of Thus, the Fontan ventricle shows systolic and diastolic
systemic ventricular dysfunction. dysfunction. It may enter into a vicious cycle whereby the
On the other hand, the main factors associated with long- low preload leads to remodelling, reduced compliance, poor
term morbidities are: ventricular filling and eventually declining cardiac output.
• Progressive ventricular dysfunction This phenomenon of progressive ‘disuse hypofunction’ occurs
• Systemic venous hypertension at a chronic preload of less than 70 percent of the “due” 657
• Right atrial distension preload.
http://vip.persianss.ir
8 The congenital malformation may itself predispose to Types
ventricular dysfunction. The morphological LV with its
ellipsoid shape and complex fiber orientation is tuned to handle The commonest arrhythmias are sinus node dysfunction
cyanotic Heart diSeaSeS
systemic pressure for a lifetime. But the morphological RV (prevalence 13–16%), intra-atrial re-entrant tachycardia
and even more the indeterminate primitive ventricle fails after (Figure 25) or atrial flutter. They are usually refractory to
few years of systemic loading. Futhermore, a tricuspid valve anti-arrhythmics and in the acute setting, quickly deteriorate
or common atrioventricular valve poorly tolerates the initial to clinical cardiac failure. Cardioversion with direct current
volume overload and starts regurgitating shortly. The treatment (DC) shock is the safest immediate therapy. Subsequently, the
of ventricular dysfunction in the setting of Fontan circuit is clinician should obtain a complete hemodynamic evaluation
very frustating for a cardiologist. Several studies, both acute in every patient with new tachycardia, as this may be the first
and chronic, have shown little impact of inotropes, afterload manifestation of pathway obstruction. Full anticoagulation
reducers, vasodilators and beta-blockers, as these have no should also be started. Long-term treatment involves
impact on the reduced preload which is the main limiting factor. medication and ablation. The best long-term treatment is
conversion of the older Fontan types to an extracardiac
arrhythmia50-52 cavopulmonary connection, together with a right atrial maze
and a reduction plasty (combined with dual chamber epicardial
The incidence of arrhythmias post-Fontan surgery ranges pacemaker if indicated). In refractory atrial tachyarrhythmias,
between 10 to 40 percent and reported even up to 10 years later. but no other indication for surgical revision, transcatheter
ablation approach may be tried with repeat procedures as
Etiology required.
Ventricular arrhythmias are extremely rare and usually
Many older Fontans have atrial wall incorporated into the caused by severe ventricular dysfunction.
circuit causing progressive atrial dilatation and wall stress;
furthermore, most of them also had atriotomy and possible Severe hypoxemia: post fontan53-56
injury to the sinus node or innervation. The lateral tunnel
technique per se is a risk factor, leading to the development Patients with a Fontan circulation are slightly desaturated
of arrhythmias due to the suture lines placed inside the with baseline pulse oximetry values 94 percent plus or minus
atrium. Heterotaxy syndromes are also prone to rhythm 2 percent. This is because the hepatic veins and coronary sinus
disorders. Bradyarrhythmias have also been observed in still drain into the atrial chambers. However, in the setting
patients undergoing the extracardiac tunnel technique. Atrial of severe desaturation, the following anatomical substrates
pacing has been suggested in order to avoid moderate degree should be ruled out: a large fenestration, intrapulmonary
bradyarrhythmias. arteriovenous fistulae and abnormal systemic venous channels
658
Figure 25: A 12-lead electrocardiogram in a post-Fontan patient with tricuspid atresia showing recurrent persistent intra-atrial
re-entrant tachycardia with a ventricular response rate of 167 beats/minute
draining into the pulmonary venous atrium (for example, a left Ventricular failure57 46
superior caval vein to the left atrium). Detailed angiography
of supra and infradiaphragmatic systemic veins should be Ventricular failure is mostly seen around 8 years after the initial
Single Ventricle
done. These connections can be occluded percutaneously in Fontan surgery, although it has been reported both earlier
the majority of cases. and later. The etiology is multifactorial like morphology of
The development of pulmonary arteriovenous malforma- dominant ventricle, valve regurgitation, etc. But the unique
tions is described in up to 25 percent of patients post-Glenn shunt feature is the combination of decreased preload and increased
leading to progressive cyanosis and exercise intolerance. The afterload (as systemic and pulmonary circulation are again in
probable etiology is exclusion of hepatoenteric flow (Factor series) in a Fontan circuit.
X) from the pulmonary circulation. These malformations Even asymptomatic patients demonstrate abnormal cardio-
are often multiple and diffuse. Recent reports noted the respiratory response to exercise which is best unmasked by
reversal of pulmonary arteriovenous malformations following Dobutamine stress test.
redirection of hepatic venous flow to the pulmonary circulation As we have discussed before in the hemodynamics
(Figures 26A and B). section, the role of inotropes, vasodilators and beta-blockers
is limited. Prompt repair of structural anomalies like
residual left-to-right Shunt atrioventricular valve regurgitation, relief of outflow tract
obstructions, correction of PA stenosis are helpful. In end-
Residual left-to-right shunt can happen due to large stage situations, orthotopic heart transplantation is the only
aortopulmonary collaterals, persistent antegrade flow from answer.
ventricle to pulmonary artery and failed occlusion of previous
shunts. A large left-to-right shunt produces volume overload thromboembolic events58,59
and stress on the single ventricle. The rule of thumb is that
if angiography of a systemic vessel gives rise to pulmonary Symptomatic systemic venous and arterial thromboembolisms
capillary blush and opacification of pulmonary veins, it should have a reported incidence of 3 to 20 percent. Literature
be occluded percutaneously. review reveals a bimodal peak of increased incidence of
a B
Figures 26a and B: Selective pulmonary angiography of the right lower lobe in a patient with tricuspid atresia and unidirectional Glenn shunt.
A. Multiple pulmonary arteriovenous malformations; B. One residual pulmonary arteriovenous malformation after transcatheter coil occlusion. 659
Courtesy: Reprinted from reference 51
http://vip.persianss.ir
8 lymphatic dysfunction60,61
Pathogenesis
cyanotic Heart diSeaSeS
Single Ventricle
occasionally useful. result. A more aggressive approach aimed at optimising the
7. Resection of the most affected part of the gut. Fontan circuit (stenting of stenosis, embolising collaterals,
8. Surgical correction of stenosed anastomotic sites, leaking conversion of older Fontans to TCPC, right atrial maze for
atrioventricular valves, late takedown, etc. carries a high intractable arrhythmias, creation of fenestration, etc.) is
mortality. needed. In refractory cases, heart transplantation is the only
9. Cardiac transplantation with consequent immunosup- option.
pressive therapy has been tried in refractory cases. This
often cures the PLE, but also has its own significant dis- SuGGeSted folloW-up of poSt-fontan patIentS
advantages.
10. Catheter interventions: Balloon dilatation/stent implan- Post-Fontan patients should be followed up by a specialist
tation of residual PA stenosis, embolization of left-to- team and the observation parameters in our institute are:
right shunts and fenestration of Fontan circuit has been • Clinical assessment including blood pressure and resting
tried in PLE. Of these, fenestration almost always im- pulse oximetry
proves PLE, but with the risk of progressive cyanosis. • 12 lead electrocardiogram
• Echocardiogram with color Doppler (Figures 28 and 29)
plastic Bronchitis and Tissue Doppler imaging
• Blood for complete blood count, prothrombin time (PT)
Plastic bronchitis is a very rare, but potentially lethal and INR (International Normalized ratio), liver function
complication occurring weeks to months after Fontan tests
surgery causing obstruction of major airways with solid • Exercise tolerance with Treadmill test
fibrinomucoid material. Persistent segmental atelectasis, • Holter monitoring if arrhythmias
large airway obstruction or expectoration of tenacious mucoid • Additional work-up include: Transesophageal
material should prompt early diagnostic and therapeutic echocardiography, cardiac MRI, cardiac catheterization
bronchoscopic lavage. Treatment is very difficult and similar and Electrophysiological study (EPS).
to PLE.
reproduction: pregnancy62,63
Most females after Fontan repair have normal menstrual
patterns. However, normal pregnancy is associated with
30 to 40 percent increase in cardiac output and circulating
blood volume and decrease in systemic vascular resistance by
24 weeks of gestation. Also a hypercoagulable state is present.
These changes lead to increase in systemic venous pressure
and may trigger right heart failure in a post-Fontan lady. The
risk of right-to-left shunt, venous thrombosis and pulmonary
embolism is increased. Successful pregnancy is rare. Studies
reveal that an oxygen saturation of lesser than 85 percent was
predictive of increased risk.
The risk of the fetus having congenital heart disease is
currently unknown, as women with cardiac malformations
amenable to Fontan surgery have rarely had offspring. For
most malformations the risk will probably vary between 5 to
10 percent.
failing fontan64,65
A Fontan circulation may become ‘failing’ and unbearable
Figure 28: Subcostal echocardiogram showing laminar flow in
because of persistent congestion with edema, low cardiac extracardiac Fontan conduit (arrow). V = Inferior vena cava
661
http://vip.persianss.ir
8 Key Messages
Single Ventricle
13. Wilkinson JL, Becker AE, Tynan M, et al. Nomenclature of the 34. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax
univentricular heart. Herz 1979;4:107-12. 1971;26:240-8.
14. Christoffels VM, Habets PEMH, Franco D, et al. Chamber 35. Kreutzer G, Galindez E, Bono H, et al. An operation for the
formation and morphogenesis in the developing mammalian correction of tricuspid atresia. J Thorac Cardiovasc Surg. 1973;
heart. Devel Biol. 2000;223:266-78. 66:613-21.
15. Cook AC, Anderson RH. The functionally univentricular 36. DeLeval MR, Kliner P, Gewillig M, et al. Total cavopulmonary
circulation: anatomic substrates as related to function. Cardiol connection: a logical alternative to atriopulmonary connection
Young. 2005;15(Suppl. 3):7-16. for complex Fontan operations. J Thoracic Cardiovasc Surg.
16. Anderson RH, Becker AE, Freedom RM, et al. Sequential 1988;96:682-95.
segmental analysis of congenital heart disease. Pediatr Cardiol. 37. Marcelletti C, Corno A, Giannico S, et al. Inferior vena cava-
1984;5:281-7. pulmonary artery extracardiac conduit. A new form of right
17. Anderson RH, Ho SY. Sequential segmental analysis – heart bypass. J Thorac Cardiovasc Surg. 1990;100:228-32.
description and categorization for the millennium. Cardiol 38. Kawashima Y, Kitamura S, Matsuda H, et al. Total cavo-
Young. 1997;7:98-116. pulmonary shunt operation in complex cardiac anomalies: a
18. Fyler DC, Buckley LP, Hellenbrand WE, et al. Report of the new operation. J Thorac Cardiovasc Surg. 1984;87:74-81.
New England Regional Infant Cardiac Program. Pediatrics. 39. de Leval MR. The Fontan circulation: a challenge to William
1980;65:375-461. Harvey? Nat Clin Pract Cardiovasc Med. 2005;2:202-8.
19. Hoffman JI, Kaplan S. The incidence of congenital heart 40. Choussat A, Fontan F, Besse B, et al. Selection criteria for
disease. J Am Coll Cardiol. 2002;39:1890-1900. Fontan’s procedure. In: Anderson RH, Shinebourne EA (Eds).
20. Van Praagh R, Ongley PA, Swan HJ. Anatomic types of single Paediatric Cardiology. New York: Churchill Livingstone;
or common ventricle in man: morphologic and geometric
1978. pp. 559-66.
aspects of 60 necropsied cases. Am J Cardiol. 1964;13:367-86.
41. Lock JE, Keane JF, Fellows KE. The use of catheter intervention
21. Gill HK, Splitt M, Sharland GK, et al. Patterns of recurrence
procedures for congenital heart disease. J Am Coll Cardiol.
of congenital heart disease: an analysis of 6,640 consecutive
1986;7:1420-3.
pregnancies evaluated by detailed fetal echocardiography.
42. Nakanishi T. Cardiac catheterization is necessary before
J Am Coll Cardiol. 2003;42:923-9.
bidirectional Glenn and Fontan procedures in single ventricle
22. Weigel TJ, Driscoll DJ, Michels VV. Occurrence of congenital
physiology. Pediatr Cardiol. 2005;26:159-61.
heart defects in siblings of patients with univentricular heart
43. Stamm C, Friehs I, Mayer JE Jr, et al. Long-term results of
and tricuspid atresia. Am J Cardiol. 1989;64:768-71.
23. Burn J, Brennan P, Little J, et al. Recurrence risks in offspring the lateral tunnel Fontan operation. J Thorac Cardiovasc Surg.
of adults with major heart defects: results from first cohort of 2001;121:28-41.
British collaborative study. Lancet. 1998;351:311-6. 44. Earing MG, Cetta F, Driscoll DJ, et al. Long-term results of the
24. Shapiro SR, Ruckman RN, Kapur S, et al. Single ventricle Fontan operation for double-inlet left ventricle. Am J Cardiol.
with truncus arteriosus in siblings. Am Heart J. 1981;102(3 Pt 2005;96:291-8.
1):456-59. 45. Gentles TL, Mayer JE, Gavreau K, et al. Fontan operation
25. Moodie DS, Ritter DG, Tajik AJ, O’Fallon WM. Long-term in five hundred consecutive patients: factors influencing
follow-up in the unoperated univentricular heart. Am J Cardiol. early and late outcome. J Thorac Cardiovasc Surg. 1997;114:
1984;53:1124-8. 376-91.
26. Ammash NM, Warnes CA. Survival into adulthood of patients 46. Bridges ND, Mayer JE, Lock JE, et al. Effect of baffle
with unoperated single ventricle. Am J Cardiol. 1996;77:542-4. fenestration on outcome of the modified Fontan operation.
27. Rigby M, et al. Two-dimensional echocardiographic categoriza- Circulation. 1992;86:1762-9.
tion of the univentricular heart: ventricular morphology, type and 47. Sommer RJ, Recto M, Golinko R, et al. Transcatheter coil
mode of atrioventricular connection. Br Heart J. 1981;46:603. occlusion of surgical fenestration after Fontan operation.
28. Freedom RM, et al. The atrioventricular junction in the univen- Circulation. 1996;94:249-52.
tricular heart: a two-dimensional echocardiographic analysis, 48. Mair D, Puga F, Danielson G. Late functional status of
Ped Cardiol. 1982;3:105. survivors of the Fontan procedure performed during the 1970s.
29. Huhta JC, et al. Two-dimensional echocardiographic spectrum Circulation. 1992;86:106-09.
of univentricular atrioventricular connection, J Am Coll 49. Khairy P, Poirier N, Mercier LA. Univentricular Heart.
Cardiol. 1985;5:149. Circulation. 2007;115:800-12.
30. Bevilacqua M, et al. Double – inlet single left ventricle: 50. Shirai LK, Rosenthal DN, Reitz BA, et al. Arrhythmias and
echocardiographic anatomy with emphasis on the morphology thromboembolic complications after the extracardiac Fontan
of the atrioventricular valves and ventricular septal defect. J operation. J Thorac Cardiovasc Surg. 1998;115:499-505.
Am Coll Cardiol. 1991;18:559. 51. Cohen MI, Wernovsky G, Vetter VL, et al. Sinus node function
31. Shiraishi H, Silverman NH. Echocardiographic spectrum after a systematically staged Fontan procedure. Circulation.
of double inlet ventricle: evaluation of the interventricular 1998;98(suppl II):352-8.
communication. J Am Coll Cardiol. 1990;15:1401. 52. Fishberger SB, Wernovsky G, Gentles T, et al. Factors that
32. Matitiau A, et al. Bulboventricular foramen size in infants with influence the development of atrial flutter after the Fontan
double – inlet left ventricle or tricuspid atresia with transposed operation. J Thorac Cardiovasc Surg. 1997;113:80-6. 663
http://vip.persianss.ir
8 53. Gatzoulis MA, Shinebourne EA, Redington AN, et al.
Increasing cyanosis early after cavopulmonary connection
by transthoracic echocardiography after the Fontan operation.
J Am Coll Cardiol. 1991;18:1733-7.
caused by abnormal systemic venous channels. Br Heart J. 60. Mertens L, Hagler DJ, Sauer U, et al. Protein-losing enteropathy
cyanotic Heart diSeaSeS
664
C hapter
PATHOLOGICAL ANATOMY
The HLHS is associated with hypoplasia of the left heart
and enlargement/hypertrophy of the right heart. Similar to
other congenital heart defects, HLHS also has a spectrum
of severity.6 In the most severe form, aortic valve and MV
are atretic, with a diminutive ascending aorta and markedly
hypoplastic LV. The MV may be atretic, hypoplastic or
severely stenotic. The atretic MV consists of fibromuscular
tissue instead of a membrane. In cases with stenotic MV, the
left ventricular cavity is usually small and may be associated
with endocardial fibroelastosis. The aortic valve may be Figure 1: Subcostal echocardiographic view of the atrial septum with
color flow imaging in an infant with hypoplastic left heart syndrome
unicuspid or bicuspid with severe stenosis or atretic. The demonstrating intact atrial septum. The flow in the superior vena cava
ascending aorta is usually hypoplastic and measures 2 to 3 mm (SVC) is shown and no patent foramen ovale is seen. LA = Left atrium;
or less in diameter. Though it is very small, it is sufficient to RA = Right atrium
http://vip.persianss.ir
8 considered to be an integral part of HLHS, although it may ventricular output to go to the lungs instead of the body.
be present in the syndrome of mitral atresia with normal Although increased pulmonary blood flow results in higher
aortic root. A patent ductus arteriosus is usually present and is oxygen saturation, systemic blood flow is compromized.
CyanotiC Heart diseases
required for survival. When the systemic blood flow decreases below a critical
Severely hypoplastic LV may also be present in hearts with level, the perfusion becomes poor and metabolic acidosis
double-outlet RV with mitral atresia, unbalanced complete and oliguria may develop. There is also decreased flow to
atrioventricular canal and other complex heart defects; in the coronary arteries and brain, with a risk of myocardial or
some studies, these variants constitute as many as 25 percent cerebral ischemia respectively. Alternatively, if pulmonary
of HLHS cases.11,12 vascular resistance is significantly higher than systemic
vascular resistance, there will be hypoxemia.
PRENATAL CIRCULATION In summary, the postnatal circulation in HLHS depends on
three major factors:
In a normally formed fetus, highly saturated inferior vena 1. Adequacy of interatrial communication.
caval blood is preferentially shunted into the left atrium via 2. Patency of the ductus arteriosus.
the patent foramen ovale and from there into the LV and aorta. 3. Level of pulmonary vascular resistance.
The superior vena caval blood containing desaturated blood
is directed towards the tricuspid valve (TV), and RV and EPIDEMIOLOGY
from there into the pulmonary arteries, ductus arteriosus and
descending aorta. By contrast, in HLHS the oxygenated blood The incidence of HLHS is 0.16 to 0.36 per 1,000 live
from the placenta is returned to the inferior vena cava (IVC) births.15 It comprises 1.2 to 1.5 percent of all congenital heart
and instead of shunting across the patent foramen ovale into defects.16, 17 HLHS accounts for 7 to 9 percent of all congenital
the left atrium, it mixes with the superior vena caval blood heart disease diagnosed in the first year of life.12 Before
in the right atrium. The pulmonary venous drainage from left surgical treatment was available, HLHS was responsible
atrium gets shunted across the atrial septum into the right for 25 percent of cardiac deaths in the neonatal period.12
atrium because of MV obstruction. Right ventricle receives The recurrence risk of HLHS in families with one affected
a mixture of vena caval and pulmonary venous and coronary child is 0.5 percent and the recurrence risk for other forms of
sinus blood.13,14 congenital heart disease in families is 2.2 to 13.5 percent.18-20
Because of widely patent ductus arteriosus and high Bicuspid aortic valve was identified in 5 to 11 percent of
pulmonary vascular resistance in the fetus, only a small portion first-degree relatives of affected probands. The incidence of
of the blood from the RV enters the lungs. Most of the blood HLHS is higher in patients with Turner syndrome, Noonan
is directed into the aorta via the ductus. Once in the aorta, syndrome, Smith-Lemli-Opitz syndrome and Holt-Oram
the blood gets distributed into the brachiocephalic vessels, syndrome. Certain chromosomal duplications, translocations
ascending aorta and descending aorta. The quantitative and deletions are also associated with HLHS.
distribution into these different vascular beds depends on their
relative vascular resistances. The ascending aortic blood flows GENDER
in a reverse direction and supplies the coronary arteries.
The HLHS is more common in males than in females, with a
POSTNATAL CIRCULATION 55 to 70 percent male preponderance.
The newborn infant with HLHS has a complex cardiovascular AGE AT PRESENTATION
physiology. Fully saturated pulmonary venous blood
returning to the left atrium cannot flow into the LV because Babies with HLHS typically present within the first 24 to
of atresia, hypoplasia, or stenosis of the MV. Therefore, 48 hours of life. Presentation occurs as soon as the ductus
pulmonary venous blood must cross the atrial septum. This arteriosus begins to constrict, which decreases the systemic
blood mixes with desaturated systemic venous blood in the blood flow, producing shock and, without intervention, causes
right atrium and from there transmitted into the RV. The RV death. Infants with pulmonary venous obstruction (absent or
then must pump this mixed blood to both the pulmonary and restrictive patent foramen ovale) may present even sooner.
the systemic circulations that are connected in parallel, rather Very rarely, an infant with persistence of high PVR and widely
than in series, by the ductus arteriosus. Blood exiting the RV open ductus arteriosus may present later, because of balanced
may flow into the lungs via the branch pulmonary arteries or pulmonary and systemic circulations.
into the body via the ductus arteriosus.
The relative flows to the pulmonary and systemic circuits MORTALITY/MORBIDITY
depend on the relative resistances of the two vascular beds.
666 Following birth, pulmonary vascular resistance (PVR) Without surgery, HLHS is uniformly fatal, usually within the
decreases, this allows a higher percentage of the right first 2 weeks of life. As alluded to above, survival for a longer
period occurs rarely and is related to persistence of the ductus infants, significant obstruction to pulmonary venous return 47
arteriosus along with balanced systemic and pulmonary (a congenitally small or absent (Figure 1) patent foramen
circulations. ovale) is usually present.
http://vip.persianss.ir
8 Evaluation of the aortic arch and thoracic aorta for evidence of
coarctation and interruption of aortic arch is important.
Doppler and color flow Doppler are important in assessing
CyanotiC Heart diseases
a B
Figures 3a and B: Two-dimensional echocardiographic precordial (A) long-axis view and (B) short axis view of the heart in a patient with
hypoplastic left heart syndrome showing the hypoplastic left ventricle (LV), an enlarged and hypertrophied right ventricle (RV) and a small
ascending aorta (AAo). Large main pulmonary artery (MPA) and patent ductus arteriosus (PDA) are also shown. AoV = Aortic valve; LA = Left
668 atrium
47
a B C
d e F
Figures 5a to F: Two-dimensional echocardiographic apical four-chamber views of the hearts of different patients with hypoplastic left heart
syndrome demonstrating varying sizes of the hypoplastic left ventricle (LV). Enlarged right ventricle (RV) and right atrium (RA) are also seen.
LA = Left atrium
669
http://vip.persianss.ir
8
CyanotiC Heart diseases
a B
Figures 6a and B: Subcostal views of the atrial septum in a patient with hypoplastic left heart syndrome demonstrating a restrictive patent
foramen ovale (PFO) (arrow) in the right-hand panel B. and turbulent flow across the PFO in the left-hand panel; A. LA = Left atrium;
RA = Right atrium
a B
Figures 7a and B: Two-dimensional echocardiographic, suprasternal notch, long-axis view of the aortic arch: A. in a patient with hypoplastic left
heart syndrome. This still frame shows markedly hypoplastic ascending aorta (AAo), serving only to deliver blood in a retrograde fashion to the
670 coronary arteries. The descending aorta (DAo) is tortuous and the appearance is suggestive aortic coarctation. Retrograde flow (arrow) in the
arch of the aorta; B. is suggestive of ductal-dependent systemic circulation
Other Lab Studies Cardiac catheterization is also a standard procedure before 47
the Fontan conversion operation. Hemodynamic data to
Complete blood count (CBC) count, WBC count with dif- calculate PVR and transpulmonary gradients are obtained to
a B
Figures 8a and B: Selected cineangiographic frames of an infant with hypoplastic left heart syndrome following Norwood procedure with
Blalock-Taussig (BT) shunt demonstrating good-sized right (RPA) and left (LPA) pulmonary arteries. A. Mild narrowing of the proximal RPA 671
(arrow) and of different infant after Norwood procedure with Sano shunt; B. Demonstrating good-sized RPA and LPA. In B, the catheter C. is
positioned into the Sano shunt via the right ventricle with its tip at the junction of Sano shunt with the pulmonary arteries
http://vip.persianss.ir
8 ready for next stage procedure, balloon dilation33-35 or stent
placement36,37 within the BT shunt can be done to improve
the oxygenation. Similar interventional procedures may also
CyanotiC Heart diseases
a B
Figures 10a and B: Selected cineangiographic frames from left internal mammary artery (LIMA) injection demonstrating collateral flow into the lungs:
A. which was completely abolished; B. after implanting two coils (C1 and C2). Sheath (Sh) in the superior vena cava inserted thorough the right
internal jugular vein in a patient with prior bidirectional Glenn procedure is seen
672
47
a B
Figures 12a and B: Selected video: A. and cineradiographic; B. frames of an infant with hypoplastic left heart syndrome demonstrating stent
placed in the markedly restrictive interatrial septum. ASD = Atrial septal defect; LA = Left atrium; RA = Right atrium; RV = Right ventricle
673
http://vip.persianss.ir
8 NATURAL HISTORY the infusion rate may be gradually decreased to a dose of
0.02 mcg/kg/minute. One should strive to maintain ductal
The natural history of untreated patients with hypoplastic left patency with the lowest effective PGE1 dose to minimize the
CyanotiC Heart diseases
heart syndrome is uniformly poor. If untreated more than 95 dose-dependent side effects of PGE1 such as hypotension,
percent infants with HLHS die within the first month of life. prompting volume resuscitation and apnea and respiratory
HLHS accounts for 25 percent of deaths due to cardiac reasons depression, requiring mechanical ventilatory support.
in the first week and 15 percent of cardiac deaths during The PVR of a newborn is slightly less than the systemic
first month of life. If pulmonary and systemic resistances vascular resistance and begins to fall soon after birth. In
are balanced, survival for 4 to 6 years has been reported the patient with HLHS, decreased PVR causes progressive
sporadically. The patients usually die from congestive heart increase in pulmonary blood flow with a concomitant decrease
failure, myocardial ischemia and pulmonary vascular disease. in systemic blood flow. When severe, this results in systemic
hypoperfusion, metabolic acidosis and shock.
MANAGEMENT After establishing ductal patency, maneuvers should be
used to minimize systemic vascular resistance and maximize
A thorough explanation of different treatment approaches— PVR. It should be noted that maneuvers to increase PVR have
supportive care, multistage surgical palliation, cardiac been more efficacious. Intubation and mechanical ventilation
transplantation, including their advantages and disadvantages, with sedation and paralysis permits hypoventilation to
should be provided to the parents. Occasionally, some anatomic elevate the partial pressure of carbon dioxide (PaCO2). The
features favor one choice over the others. In the presence of chief metabolic factor that appears to influence pulmonary
severe TV or pulmonary valve anomalies, the multistage resistance in patients with HLHS is arterial PCO2 and should
surgical approach is not likely to be beneficial; cardiac be maintained in the range of 45 to 50 mm Hg. Metabolic
transplantation is the only surgical choice. In most cases, the acidosis should be corrected with sodium bicarbonate. The
choice of treatment is based on the parents’ preference. While hematocrit should be maintained between 40 to 45 percent
such a decision is being made, the infant should be stabilized to provide adequate oxygen carrying capacity and to increase
as discussed in the next section. the blood viscosity; the latter may also serve to elevate PVR.
If supportive care is chosen by the parents, they need strong Supplemental oxygen to increase the oxygen saturations
emotional support, because the condition is fatal without should be avoided.
active treatment. Subambient oxygen (FIO2 of 15–19%) with supplemental
nitrogen or carbon dioxide may be used to elevate PVR;
Preoperative Medical Care although this is an attractive concept, it should not be pursued
for long periods, because severe pulmonary hypertension may
In situations where prenatal diagnosis of HLHS by fetal complicate the postoperative course. However, this does not
echocardiography is made, it is advisable to have the baby seem to adversely affect the pulmonary vasculature on long-
deliver at an institution, where tertiary care, including term follow-up.50
neonatal cardiac surgery, is performed routinely. There was Because of obstruction at the mitral valve, pulmonary
some suggestion in the past that elective cesarean delivery venous blood must cross the atrial septum via a patent
may provide better outcomes. A recent study examining this foramen ovale (PFO) and mix with desaturated systemic
issue found that there was no hemodynamic advantage for venous blood in the right atrium. In some patients, the PFO
elective cesarean delivery section over vaginal delivery.49 may be restrictive. Mild restriction is acceptable and may be
Successful preoperative management encompasses address- beneficial in that it may maintain high PVR and promote good
ing three main aspects: systemic flow. Severe restriction may cause severe hypoxemia
1. Providing adequate systemic flow. and pulmonary edema. Periodic monitoring by echo-Doppler
2. Limiting pulmonary overcirculation. studies is recommended. In contrast to other patients with
3. Provide adequate egress of pulmonary venous return from HLHS, the patients with severe obstruction at PFO and
the left atrium. patients with intact septum do not show diastolic flow reversal
In HLHS, the blood flow to systemic circulation (coronary in the ductus arteriosus. When severe restriction develops,
arteries, brain, liver and kidneys) mainly depends on the transcatheter interventions to enlarge the atrial septal defect
patency of ductus arteriosus. Treatment with PGE1 should be may be performed. While Rashkind balloon septostomy and
initiated immediately after HLHS is diagnosed or suspected, Park blade septostomy are conventional methods to open atrial
to establish ductal patency and ensure adequate systemic septum, these may not be feasible because of hypoplastic left
perfusion. The patient’s physiologic state often directs initial atrium. Static dilatation of the atrial septum25-27 with a balloon
PGE1 dosing. For patients who present in shock with suspected angioplasty catheter may be used, which may not only relieve
ductal closure or a restrictive duct, initial dose will range from the obstruction, but also keep some restriction such that there
674 0.05 to 0.1 mcg/kg/minute. Once ductal patency is ensured, is no rapid fall in the pulmonary vascular resistance. Rarely
stent implantation25,28,29 may become necessary. Sometimes, 3. Anastmosis of the main pulmonary artery to the aorta with 47
it may be impossible to stabilize them medically or in the or without homograft material in order to provide systemic
cardiac catheterization laboratory and such patients may blood flow.
http://vip.persianss.ir
8 The combination of AV oxygen saturation difference and systemic pressures. In the presence of aortic obstruction, the
echocardiographic evaluation of ventricular function and right ventricular systolic function may decrease rapidly. The
AV valve regurgitation is important in establishing the physical examination and femoral pulses can be misleading in
CyanotiC Heart diseases
cause and initiation of treatment. Infant with decreased these cases, because of obligatory runoff through the systemic
ventricular function may benefit from increasing the to pulmonary artery shunt.
inotropic support, where as infants with adequate function, The incidence of interstage mortality is 5 to 15 percent.65
but high QP : QS benefit from maneuvers to increase the The presence of a restrictive atrial communication, aortic arch
PVR and/or by lowering the systemic vascular resistance. obstruction, obstructed shunt flow, pulmonary artery distortion
2. Cyanosis: The possible reasons for cyanosis include, and AV valve insufficiency are associated with interstage
a. Pulmonary venous desaturation from lung pathology mortality.65 Commonly acquired childhood gastrointestinal
(pneumothorax, pleural effusion, pneumonia, infection, or respiratory diseases, which result in hypovolemia and/
pulmonary edema) or acute hypoxemia have also been implicated as causes for
b. Systemic venous desaturation (anemia, low systemic interstage death.65 After successful stage I palliation, any
cardiac output) of the above-mentioned pathologic processes can lead to
c. Decreased pulmonary blood flow (elevated PVR, increased metabolic demands and an unfavorable oxygen
pulmonary venous hypertension, restrictive the atrial supply/demand relationship, placing the infant with minimal
septal defect, distortion of pulmonary arteries, small or myocardial reserve at even greater risk for mortality, until
occlusion of systemic to pulmonary artery shunt). progression to cavopulmonary anastomosis. Therefore,
Pulmonary venous desaturation is evaluated typically transitioning infants to home after stage I palliation warrants
with chest radiograph and auscultation. Systemic venous ongoing vigilance well beyond the initial early postoperative
desaturation can be evaluated by mixed venous oxygen period. Careful home surveillance and optimal nutrition with
saturation and hemoglobin and hematocrit. Sometimes good growth may reduce inter-stage mortality.66,67
cardiac catheterization may be necessary to identify the
anatomic (shunt related) or physiologic (PVR related) Bidirectional Glenn Procedure (Stage II)
causes of decreased QP : QS ratio.
3. High oxygen saturation: Infants with high oxygen Bidirectional Glenn procedure is usually performed 6 months
saturations more than 90 percent, typically have low PVR following Norwood procedure. Prior to bidirectional Glenn,
and pulmonary blood flow in excess of systemic blood cardiac catheterization is performed to assess right ventricular
flow. Also, evaluation for arch obstruction is important, function, pulmonary artery size and anatomy, PVR and
since distal obstruction will force more blood through the coarctation of the aorta. Transcatheter occlusion of collateral
shunt and increase the Qp at the expense of Qs. vessels, balloon angioplasty/stent of branch pulmonary artery
In the intensive care unit, the management mainly depends stenosis and balloon angioplasty of aortic coarctation are
on optimizing the cardiac output (inotropic and lusitropic performed as indicated.
support) and optimizing the nutrition as soon as possible and The bidirectional Glenn procedure consists of performing
removing the unnecessary indwelling catheters early. Since an anastomosis between the SVC and the right pulmonary
the babies with HLHS may not have been fed orally prior to artery, end-to-side, so that venous return from the upper part
surgery, suck and swallow coordination may be delayed. of the body flows directly into both lungs. If a persistent
left SVC is present, especially in the absence of or a small
Follow-up: Upon hospital discharge, most infants receive bridging innominate vein, bilateral bidirectional Glenn shunts
digoxin to augment cardiac function, minimal diuretics to help should be performed. In the hemi-Fontan, the SVC-right atrial
manage right ventricular volume overload and aspirin to prevent junction is either closed with a patch or SVC is constricted
thrombosis of the shunt. If significant tricuspid regurgitation is with polydioaxanone thread that is reopened during the next
present, afterload reduction with captopril11 should be used. stage. Blood from the IVC continues to drain into the right
Caution should be exercised in patients receiving diuretic atrium. The BT or Sano shunt that was placed at stage I is
therapy to avoid intravascular volume depletion that might liagated.
reduce total cardiac output, as well as increase the risk of Repair of pulmonary artery narrowing, if present and
shunt thrombosis owing to hyperviscosity. Oxygen saturation addressing TV regurgitation, restrictive atrial septum and
is typically 70 to 80 percent in room air and should not be any other abnormalities should be undertaken at the time of
of concern. Periodic (every 4 week or as clinically indicated) bidirectional Glenn.
cardiology evaluations are essential for detection of potential
complications such as aortic arch obstruction, adequacy of Follow-up after stage II: The follow-up after bidirectional
the BT or Sano shunt, atrial septal defect obstruction and Glenn is also necessary, although the infants are more stable
significant tricuspid regurgitation. In patients with HLHS after than after Norwood. Interstage mortality68 also exists, but not
676 Norwood, the RV is volume overloaded and has to generate as high as seen between stages I and II.
Fontan Procedure (Stage III) in total cavopulmonary connections. Obstructed pulmonary 47
outflow pathways, persistent shunts and systemic venous
Fontan procedure is performed approximately 12 months after congestion including protein-losing enteropathy45,74 may
http://vip.persianss.ir
8
CyanotiC Heart diseases
B
Figures 13a and B: Selected cineangiographic frames from a conduit angiogram in a patient who had a fenestrated Fontan procedure
demonstrating right-to-left shunt across the fenestration opacifying the left atrium which was successfully occluded with an Amplatzer device;
B. with no residual shunt. Previously implanted stent (St) to relieve left pulmonary artery stenosis and coil (C) to occlude collateral vessel and
sternal (S) wires are also seen. PC = Pigtail catheter in the descending aorta; RPA = Right pulmonary artery
of graft rejection, frequent outpatient surveillance to identify bidirectional Glenn shunt performed. This appears to shift
rejection early and multiple hospitalizations for treatment of some of the early mortality of Norwood to stage II. This is
infection and suspected rejection. Periodic endomyocardial followed by Fontan conversion with an extracardiac conduit.
biopsy is required for more precise monitoring. However, Although reduction of early mortality is theoretically feasible,
the long-term survival following both surgical approaches is larger experience with this approach than is currently available
similar. At most institutions heart transplantation is no longer is necessary prior to general adaptation of this method of
the first option for management of HLHS patients. management of all HLHS patients. Some comparisons of
hybrid with conventional Norwood84,85 did not demonstrate
EMERGING THERAPIES significant difference. Other new approaches such as double
shunt technique for hybrid palliation86 are being attempted.
Hybrid Approach to Hypoplastic Left Heart Syndrome
Prevention by Fetal Intervention
Banding of both the branch pulmonary arteries via median
sternotomy and implanting stent in the ductus arteriosus is Fetal echocardiographic studies have shown development of
performed initially.83 At the time of the second stage, aortic HLHS in fetuses initially found to have severe/critical aortic
678 arch is reconstructed, atrial septectomy carried out and stenosis. Fetal intervention to relieve aortic valve stenosis
47
(by balloon aortic valvuloplasty) may promote normal actuarial survival rate after staged reconstruction is 70 percent
development of the LV.87 Further experience/research into this at 5 years. Neurodevelopmental prognosis is not known; how-
type of approach is needed. ever, abnormalities are reported.91,92 Approximately 20 percent
of infants listed for cardiac transplantation die, while waiting for
Catheter-assisted Fontan a donor heart. After successful transplantation, the survival rate
at 5 years is approximately 80 percent. When the preoperative
Konert et al88 proposed a staged surgical-catheter approach; mortality is considered, the overall survival rate after cardiac
they performed a modified hemi-Fontan procedure instead transplantation is approximately 70 percent, or similar to the re-
of bidirectional Glenn shunt that is later completed by sults for staged reconstruction.
transcatheter methodology. This reduces the total number of
operations required. This concept has not been tried for post- SUMMARY AND CONCLUSION
Norwood HLHS patients.
Hypoplastic left heart syndrome (HLHS) is an assortment
PROGNOSIS of left heart anomalies including a very small left ventricle
with under development of the mitral and aortic valves and
The survival rate of infants treated with both multistage a small and hypoplastic aorta. A patent foramen ovale and a
surgery and cardiac transplantation is similar to that of infants patent ductus arteriosus are usually present and are necessary
with other complex forms of congenital heart disease in which a for survival. Coarctation of the aorta may also be present.
two-ventricle repair is not possible. The major mortality is at the Pulmonary venous blood crosses the atrial septum and mixes
time of Norwood, stage I. Overall survival at hospital discharge with systemic venous blood in the right atrium and from there
after the Norwood procedure is nearly 75 percent.89 Success rates passed on into the right ventricle and the pulmonary artery.
are higher in uncomplicated cases and lower in cases in whom The pulmonary and the systemic circulations are connected
significant preoperative risk factors are present, such as age in parallel by the ductus arteriosus and the blood exiting the
greater than 1 month, significant tricuspid insufficiency, pul- right ventricle is distributed into the lungs via the branch
monary venous hypertension, associated major chromosomal pulmonary arteries and into body via the ductus arteriosus.
or noncardiac abnormalities, prematurity and high Aristotle HLHS comprises 1.2 to 1.5 percent of all congenital heart de-
scores (> 20).90 Survival after the bidirectional Glenn/hemi- fects and is a uniformly lethal unless it is promptly identified,
Fontan and Fontan operations is nearly 90 to 95 percent. The treated with PGE1 and surgically palliated. They are clinically 679
http://vip.persianss.ir
8 identified either by prenatal ultrasound or present after birth 10. Rychik J, Rome JJ, Collins MH, et al. The hypoplastic left
heart syndrome with intact atrial septum: atrial morphology,
with symptoms as the ductus begins to close. The time of
presentation depends on the degree of atrial level obstruction, pulmonary vascular histopathology and outcome. J Am Coll
CyanotiC Heart diseases
ductal patency and the level of pulmonary vascular resistance. Cardiol. 1999;34:554-60.
11. Rao PS, Striepe V, Merrill WH. Hypoplastic left heart syndrome.
The diagnosis can usually made with echo-Doppler studies.
In: Kambam J (Ed). Cardiac Anesthesia for Infants and Children.
The initial management of HLHS is by prompt infusion of
St Louis, MO: Mosby-Year Book 1994. pp. 296-309.
PGE1 to keep the ductus open. Balancing the pulmonary and 12. Norwood WI Jr. Hypoplastic left heart syndrome. Ann Thorac
systemic circulation to maintain sufficient systemic perfusion Surg. 1991;52:688-95.
and ensuring adequacy of the patent foramen ovale for easy 13. Rudolph AM. Congenital Diseases of the Heart. Chicago: Year
egress of the left atrial blood while waiting for surgery are the Book Medical; 1974.
next tasks. 14. Rao PS. Fetal and neonatal circulation. In: Kambam J (Ed).
Surgical management is either by multistage surgical proce- Cardiac Anesthesia for Infants and Children. St Louis, MO:
dures, consisting of Norwood procedure (stage I) in the neonatal Mosby-Year Book; 1994. Chapter 2. pp. 10-19.
15. Fyler DC. Report of the New England Regional Infant Cardiac
period, hemi-Fontan or bidirectional Glenn procedure (stage II)
Program. Pediatrics. 1980;65:375-461.
at about six months of age, and Fontan conversion (stage III)
16. Freedom RM. Aortic atresia. In: Keith JD, Rowe RD, Vlad P.
one or more years later or by orthotopic heart transplantation. (Eds). Heart Disease in Infants and Children, 3rd edition. New
Currently, the actuarial survival rate of infants treated with these York: Mcmillian; 1978.
surgical approaches is 70 percent at 5 years and is similar to that 17. Fyler DC. Prevalence trends. In: Fyler DC. (Ed). Nadas‘
of infants with other complex forms of congenital heart disease Pediatric Cardiology, Philadelphia: Hanley and Belfus; 1992.
in whom a two-ventricle repair is not possible. Continued fol- 18. Holmes LB, Rose V, Child AH. Comment on hypoplastic left
low-up both after Fontan conversion and orthotopic heart trans- heart syndrome. In: Daniel Bergsma (Ed). Clinical Delineation
plantation is mandatory to address problems associated with of Birth Defects, Part 16: Urinary System and Others.
Baltimore: Williams and Wilkins; 1972. pp. 228-30.
both these modalities of treatment.
19. Nora JJ, Nora AH. Genetics and Counseling in Cardiovascular
Diseases. Springfield, IL: Charles C Thomas Publisher; 1978.
Disease is war with the laws of our being, and all war, as a 20. Boughman JA, Berg KA, Astemborski JA, et al. Familial
great general has said, is hell. risks of congenital heart defect assessed in a population-based
— Lewis G Janes epidemiologic study. Am J Med Genet. 1987;26:839-49.
21. Sihha SN, Rusnak SL, Sommers HM, et al. Hypoplastic left
ventricle syndrome. Analysis of 30 autopsy cases in infants
REFERENCES with surgical considerations. Am J Cardiol. 1968;21:166.
22. Galindo A, Nieto O, Villagra S, et al. Hypoplastic left heart
1. Noonan JA, Nadas AS. The hypoplastic left heart syndrome an syndrome diagnosed in fetal life: associated findings, pregnancy
analysis of 101 cases. Pediat Clinics North Am. 1958;5:1029. outcome and results of palliative surgery. Ultrasound Obstet
2. Lev M, Arcilla R, Rimoldi HJ, et al. Premature narrowing or Gynecol. 2009;33:560-66.
closure of foramen ovale. Am Hear J. 1963;65:638. 23. Rashkind WJ, Miller WW. Creation of an atrial septal defect
3. Norwood WI, Kirklin JK, Sanders SP. Hypoplastic left heart without thoracotomy. A palliative approach to complete trans-
syndrome: experience with palliative surgery. Am J Cardiol. position of the great arteries. 1966;196:991-92.
1980;45:87-91. 24. Park SC, Neches WH, Zuberbuhler JR, et al. Clinical use of
4. Norwood WI, Lang P, Hansen DD. Physiologic repair of blade atrial septostomy. Circulation. 1978;58:600-06.
aortic atresia-hypoplastic left heart syndrome. N Engl J Med. 25. Rao PS. Role of interventional cardiology in neonates: Part
1983;308:23-26. I. Non-surgical atrial septostomy. Congenital Cardiol Today.
5. Bailey L, Concepcion W, Shattuck H, et al. Method of heart 2007;5(12):01-12.
transplantation for treatment of hypoplastic left heart syndrome. 26. Shrivastava S, Radhakrishnan S, Dev V, et al. Balloon dilatation
J Thorac Cardiovasc Surg. 1986;92:01-05. of atrial septum in complete transposition of great artery—a new
6. Bharati S, Lev M. The surgical anatomy of hypoplasia of aortic technique. Indian Heart J. 1987;39:298-300.
tract complex. J Thorac Cardiovasc Surg. 1984;88:97-101. 27. Rao PS. Static balloon dilatation of the atrial septum. Am Heart
7. Von Rueden TJ, Knight L, Moller JH, et al. Coarctation of J. 1993;125:1826.
the aorta associated with aortic valvular atresia. Circulation. 28. Rao PS. Interventional pediatric cardiology: state of the art and
1975;52:951-54. future directions. Pediat Cardiol. 1998;19:107-24.
8. Jonas RA, Lang P, Hansen D, et al. First-stage palliation of 29. Atz AM, Feinstein JA, Jonas RA, et al. Preoperative
hypoplastic left heart syndrome. The importance of coarctation management of pulmonary venous hypertension in hypoplastic
and shunt size. J Thorac Cardiovasc Surg. 1986;92:6-13. left heart syndrome with restrictive atrial septal defect. Am J
9. Chin AJ, Weinberg PM, Barber G. Subcostal two-dimensional Cardiol. 1999;83:1224-28.
echocardiographic identification of anomalous attachment 30. Brockenbrough EC, Braunwald E, Ross J Jr. Transseptal left
of septum primum in patients with left atrioventricular valve heart catheterization. A review of 450 studies and description of
underdevelopment. J Am Coll Cardiol. 1990;15:678-81. an improved technique. Circulation. 1962;25:15-22.
680
31. Duff DF, Mullins CE. Transseptal left heart catheterization
in infants and children. Cathet Cardiovasc Diagn. 1978;4:
49. Peterson AL, Quartermain MD, Ades A, et al. Impact of mode of
delivery on markers of perinatal hemodynamics in infants with
47
213-23. hypoplastic left heart syndrome. J Pediatr. 2011;159:64-69.
http://vip.persianss.ir
8 hypoplastic left heart syndrome. Cardiol Young. 2011;21: 80. Estner HL, Kolb C, Schmitt C, et al. Long-term transvenous
59-64. AV-sequential pacing in a failing atriopulmonary Fontan
67. Hansen JH, Furck AK, Petko C, et al. Use of surveillance patient. Int J Cardiol. 2008;127:e93-95.
CyanotiC Heart diseases
criteria reduces interstage mortality after the Norwood operation 81. Gamba A, Merlo M, Fiocchi R, et al. Heart transplantation in
for hypoplastic left heart syndrome. Eur J Cardiothorac Surg. patients with previous Fontan operations. J Thorac Cardiovasc
2012;41:1013-18. Surg. 2004;127:555-62.
68. Carlo WF, Carberry KE, Heinle JS, et al. Interstage attrition 82. Jayakumar KA, Addonizio LJ, Kichuk-Chrisant MR, et al.
between bidirectional Glenn and Fontan palliation in children Cardiac transplantation after the Fontan or Glenn procedure. J
with hypoplastic left heart syndrome. J Thorac Cardiovasc Am Coll Cardiol. 2004;44:2065-72.
Surg. 2011;142:511-16. 83. Galantowicz M, Cheatham JP. Lessons learned from the
69. Marcelletti C, Corno A, Giannico S, et al. Inferior vena cava- development of a new hybrid strategy for the management of
pulmonary artery extracardiac conduit. A new form of right hypoplastic left heart syndrome. Pediatr Cardiol. 2005;26:
heart bypass. J Thorac Cardiovasc Surg. 1990;100:313-14. 190-99.
70. Choussat A, Fontan F, Besse P, et al. Selection criteria for 84. Photiadis J, Sinzobahamvya N, Hraška V, et al. Does bilateral
Fontan procedure. In: Anderson RH, Shinebourne EA (Eds) pulmonary banding in comparison to Norwood procedure
Paediatric Cardiology. Edinburgh: Churchill Livingstone; improve outcome in neonates with hypoplastic left heart
1978. p. 559. syndrome beyond second-stage palliation? A review of the
71. Billingsley AM, Laks H, Boyce SW, et al. Definitive repair in current literature. Thorac Cardiovasc Surg. 2012;60:181-88.
some patients with pulmonary atresia with intact ventricular 85. Hsia TY, Cosentino D, Corsini C, et al. Modeling of Congenital
septum. J Thorac Cardiovasc Surg. 1989;97:746-54. Hearts Alliance (MOCHA) Investigators. Use of mathematical
72. Laks H, Pearl JM, Haas GS, et al. Partial Fontan: advantages modeling to compare and predict hemodynamic effects between
of an adjustable interatrial communication. Ann Thorac Surg. hybrid and surgical Norwood palliations for hypoplastic left
1991;52:1084-94. heart syndrome. Circulation. 2011;124(11 Suppl):S204-10.
73. Bridges ND, Lock JE, Castaneda AR. Baffle fenestration 86. Jatene MB, Oliveira PM, Moysés RA, et al. Double shunt
with subsequent transcatheter closure: Modification of the technique for hybrid palliation of hypoplastic left heart
Fontan operation for patients with increased risk. Circulation. syndrome: a case report. J Cardiothorac Surg. 2011;6:146.
1990;82:1681-89. 87. Tworetzky W, Wilkins-Haug L, Jennings RW, et al. Balloon
74. Rao PS, Turner DR, Forbes TJ. Hypoplastic Left Heart dilation of severe aortic stenosis in the fetus: potential for
Syndrome. eMedicine from WebMD. Updated September 22, prevention of hypoplastic left heart syndrome: candidate
2009. Available at: http://emedicine.medscape.com/article/ selection, technique, and results of successful intervention.
890196-overview. Circulation. 2004;110:2125-31.
75. Kreutzer J, Graziano JN, Stapleton G, et al. Late catheter 88. Konertz W, Schneider M, Herwig V, et al. Modified hemi-
interventions in hypoplastic left heart syndrome. Cardiol Fontan operation and subsequent nonsurgical Fontan
Young. 2011;21:65-76. completion. J Thorac Cardiovasc Surg. 1995;110:865-67.
76. Goff DA, Blume ED, Gauvreau K, et al. Clinical outcome of 89. Bove EL. Current status of staged reconstruction for hypoplastic
fenestrated Fontan patients after closure: the first 10 years. left heart syndrome. Pediatr Cardiol. 1998;19:308-15.
Circulation. 2000;102:2094-99. 90. Sinzobahamvya N, Photiadis J, Kumpikaite D, et al.
77. Boudjemline Y, Bonnet D, Sidi D, et al. Closure of extracardiac Comprehensive Aristotle score: implications for the Norwood
Fontan fenestration by using the Amplatzer duct occluder. Arch procedure. Ann Thorac Surg. 2006;81:1794-800.
Mal Coeur Vaiss. 2005;98:449-54. 91. Newburger JW, Sleeper LA, Bellinger DC, et al. (Pediatric
78. Jacobs ML, Rychik J, Byrum CJ, Norwood WI Jr. Protein- Heart Network Investigators). Early developmental outcome
losing enteropathy after Fontan operation: resolution after in children with hypoplastic left heart syndrome and related
baffle fenestration. Ann Thorac Surg. 1996;61:206-08. anomalies: the single ventricle reconstruction trial. Circulation.
79. Lopez JA. Transvenous right atrial and left ventricular 2012;125:2081-91.
pacing after the Fontan operation: long-term hemodynamic 92. Carotti A. Postoperative neurodevelopmental outcome of
and electrophysiologic benefit of early atrioventricular patients with hypoplastic left heart complex: hybrid versus
resynchronization. Tex Heart Inst J 2007;34:96-101. Norwood strategy. Eur J Cardiothorac Surg. 2012;42:40-41.
682
Sec t i on
Congenital
Cardiomyopathies
http://vip.persianss.ir
C hapter
48 Dilated Cardiomyopathy
http://vip.persianss.ir
9 Box 1: Causes of dilated cardiomyopathy
all three factors interplay to a different extent. Myocyte
injury due to various factors enlisted in Box 1, myocarditis,
• Ischemic cardiomyopathy (must be excluded) autoimmune mechanism triggered secondary to myocardial
Congenital cardiomyopathies
A C D
Figures 1 A to D: DCM-Gross/Micro: A. Globular appearance of the heart due to dilatation of right and left ventricles. The apex is rounded and
formed by both ventricles. B. Multiple pale brown thrombi (arrow) attached to the endocardium of dilated right ventricle (RV). TV = Tricuspid
686 valve; C. Large fresh mural thrombus (arrow) attached to the septal region of left ventricle (LV). D. The striking feature is an increase in the
interfiber connective tissue with stretched and attenuated fibers. Note: Presence of large nuclei indicative of accompanying hypertrophy. Ao =
Aorta; AV = Aortic Valve; PT = Pulmonary trunk; RA = Right Atrium; RAA = Right atrial appendage; TV = Tricuspid valve; Courtsey: Dr Pradeep
Vaideeshwar
48
Dilated Cardiomyopathy
Figure 2: Neurohormonal activation in heart failure.
men than in women. In children, the yearly incidence is 0.47 In idiopathic DCM, 70 to 95 percent have frequent and
cases per 100,000 per year overall, but it is higher in boys complex ventricular premature complexes (VPCs) and 40 to
than in girls (1.32 vs 0.92 cases per 100,000, p < 0.001) and in 80 percent have unsustained ventricular tachycardia (VT). In
babies younger than 1 year than in children (8.34 vs cases per VHeFt study 25 to 30 percent of patients with unsustained VT
100,000, 95 percent confidence interval 7.21 to 9.61).10 did not have symptoms.12
Physical findings depend upon the severity of LV dysfunction
Clinical Features as well as right ventricular dysfunction. If cardiac output is
reduced, low arterial pressure, tachycardia and cool extremities
Patients may present in early childhood, though most present develop. Bilateral basal crepitations due to pulmonary venous
during the 4th and 5th decades of life. congestion may be evident in auscultation. The apex beat may
In general, symptoms are manifested when disease has be displaced laterally due to the dilated LV. Auscultation of the
progressed to end-stage with significant myocardial fibrosis. heart may reveal S3 and/or systolic murmur of MR secondary
Symptoms related to congestive heart failure such as dyspnea, to LV dilation. Right ventricle involvement presents with signs
fatigue, angina, pulmonary congestion and low cardiac output and symptoms of venous congestion and a murmur of tricuspid
are the usual presenting features. Suspicion of myocarditis regurgitation. Cachexia and peripheral edema typically arise
and postinfectious DCM may be raised by the presence of late in the course of the disease. Additionally, peripheral edema
chest pain, exertional dyspnea, fatigue, syncope, palpitations, and ascites are late signs in children.
ventricular tachyarrhythmias and conduction abnormalities or
by acute congestive heart failure/cardiogenic shock associated Thromboembolism
with LV dilation and/or segmental wall motion abnormalities
and ST-T changes on electrocardiogram (ECG). Angina is a Thromboembolism often complicates the clinical course of
feature frequently found in parvovirus B19-associated heart patients with DCM and could be the first presentation. At least
disease.11 11 to 13 percent patients experience embolic episodes. Emboli
The disease is usually progressive. Mitral regurgitation occur in order of decreasing frequency in pulmonary, renal,
and ventricular arrhythmias can develop in the course of spleen or cerebral circulations.13
the disease. MR is secondary to LV dilatation. Ventricular
arrhythmias have been associated with myocardial fibrosis Diagnosis
and hemodynamic stress, both of which contribute to
re-entry phenomenon critical to the development of Diagnosis is dependent on patient’s history, clinical examina-
arrhythmias. About 40 percent of DCM patients die suddenly. tion and imaging, i.e. echocardiography or cardiac magnetic
687
http://vip.persianss.ir
9 resonance imaging (MRI) features of DCM or heart failure also helps in assessing the severity of the disease.14 These
or both. features are included in Box 2.
Congenital cardiomyopathies
Dilated Cardiomyopathy
A
B
Figures 3A and B: A. 12-lead electrocardiogram (ECG) in a 13-year-old boy with DCM shows sinus tachycardia with left axis with poor R wave
progression; B. ECG in an 11-year-old boy with DCM shows normal sinus rhythm with normal axis, right bundle branch block, q waves in lateral
leads and fractioned QRS inferior leads suggestive of scarring
A B
Figures 4A and B: A. The M-mode in 5-year-old boy of DCM shows dilated left ventricle (LV); B. Apical four-chamber view shows
dilated left atrium (LA), LV with a ejection fraction of 38 percent. RA = Right Atrium; RV = Right Ventricle. Courtsey: Dr IB Vijayalakshmi 689
http://vip.persianss.ir
9
Congenital cardiomyopathies
A B
Figure 5A and B: A. Transthoracic echocardiography in apical four chamber view in a 12-year-old girl with dilated cardiomyopathy with reduced
left ventricular (LV) function (EF - 30%) shows dilated spherical LV with a organised clot in the apex. B.Spontaneous echo contrast (SEC) is seen
due to the sluggish circulation. LA = Left atrium; LV = Left ventricle.RA = Right atrium; RV = Right ventricle. Image courtsey: Dr IB Vijayalakshmi
approach sometimes enables improved treatment strategies A cardiac MRI should also include late-enhancement
and accuracy of prognosis. images, which are important for tissue-characterization
and can help differentiate dilated ischemic CMP from non-
Magnetic Resonance Imaging ischemic DCM.
Dilated Cardiomyopathy
disease as well as systemic hypotension and evidence of fluid sustains these levels. Hence, the combination is associated
retention. β-blockers with intrinsic sympathomimetic activity with vasodilatation and reduced afterload, but the mortality
and agents like bucindolol have not shown survival benefit.24,25 reduction is less than that of ACEIs and ARBs.25 In patients
Clinical trials have shown a dose dependent improvement with renal insufficiency, or persistent hypertension in the
in LV function and reduction in mortality and hospitalizations presence of optimal doses of β-blockers and ACE-inibitors
with β-blocker use. Thus, β-blocker dose should be started addition of a fixed dose isosorbide dinitrate (37.5 mg
in a very low dose and the dose should be doubled every 2 hydralazine and 50 mg isosorbide dinitrate) and hydralazine
weeks until the target dose is reached or symptoms become combination is associated with improved survival and
limiting. The patient should be informed that β-blockers may decreased hospitalization as seen in A-HeFt trial.29,30
lead to an increase in symptoms for 4 to 10 weeks before any
improvement. Though inpatient initiation is associated with Digoxin
a higher compliance, it should not be initiated on patients
with minimal evidence of fluid retention or those on recent Digoxin has a sympathoinhibitory effect and Digitalis
intravenous therapy. Investigation Group (DIG) trial has demonstrated a reduction
in hospitalization for heart failure. No mortality benefit was
Angiotensin Receptor Blockers seen and the benefit in women was less than that for men.
Hence, the addition of a low dose of the drug may benefit
A large meta-analysis of 24 randomized trials showed symptomatic patients and trough digoxin levels should be
superiority of angiotensin receptor blockers (ARBs) to checked to minimize the risk of toxicity.31
placebo in patients with intolerable side effects with ACE-
inhibitors and their non-inferiority to all cause mortality or Statins
hospitalizations when compared to ACE inhibitors. Valsartan
Heart Failure Trial (Val-HeFT) suggested that addition of Dilated cardiomyopathy is a multifactorial and progressive
valsartan in patients already receiving treatment with ACEIs disease indicating that important pathogenetic mechanism
and β-blockers was associated with a worse outcome. Thus, remain active and unmodified by currently available treatment.
neurohormonal blockade beyond a certain extent is not In view of probable role of cytokines and inflammation in
associated with any benefit, but may be harmful.26,27 DCM, statins with their pleiotropic effect may provide an
alternative treatment option in patients with this condition.
Aldosterone Antagonists In the universe (RosUvastatiN Impact on VEntricular
Remodeling, LipidS, and CytokinEs) study, high-dose
The elevated aldosterone levels seen in patients with heart rosuvastatin (40 mg/day) did not result in a significant
failure promote sodium retention, electrolyte imbalance improvement in LV ejection fraction relative to placebo.
as well as endothelial dysfunction leading to myocardial Attorvastatin 80 mg has been shown improvement in the LV
fibrosis. Both the selective agent eplerenone and non-selective function and excercise tolerence in DCM due to improvement
antagonist spironolactone significantly reduce the mortality in endothelial dysfunction and anti inflamatory effects.
and hospitalizations. These should be introduced in New York Candidates for statin therapy with DCM should be in New
Heat Association (NYHA) Class III and IV patients, but one York Heart Association Class II or III and should have normal
must monitor potassium levels carefully.28 or increased levels of lipid.32
Diuretics Complications
Goal of diuretic therapy is to eliminate clinical evidence of Complications such as arrhythmias and thromboembolic
fluid retention, such as elevated jugular pressure and peripheral events can be reduced with prophylactic medications. Rate
edema. The most commonly used loop diuretics is furosemide. control in atrial fibrillation can be achieved by β-blockers and
Bumetanide and torsemide are more potent and may be started. digoxin. Avoid calcium channel blockers. If symptoms persist,
Thiazide diuretics may be added for a synergistic effect, if then Class III antiarrhythmic drugs defetilide and amiodarone
clinically indicated. The diuretic dose needs to be carefully have been found to be safe and effective.33 Amiodarone is
adjusted as a higher dose can cause volume depletion and another medication that clinicians may use to treat arrhythmias,
precipitate ACE inhibitor-induced hypotension, while lower such as atrial fibrillation and supraventricular arrhythmias,
dosing can lead to recurrence of symptoms. Therefore, the there is no benefit in mortality in patients with ventricular
therapy has to be tailored to each patient and they should be arrhythmias.34 Reduction of thrombus formation within the 691
educated to daily monitor their weight and regulate the dose. dilated chambers may be necessary to prevent thromboembolic
http://vip.persianss.ir
9 events. Anticoagulants, such as warfarin, are indicated for adsorption and subsequent IgG substitution improved cardiac
patients with a history of previous thromboembolic events, function, hemodynamic parameters (cardiac and stroke
severe systolic dysfunction or ventricular dilatation, though volume index) and systemic vascular resistance .
Congenital cardiomyopathies
the benefits for warfarin treatment must outweigh the risks. The tailored immunosuppressive inflammatory cardio-
myopathy (TIMIC-immunosuppressive therapy in patients
Immune-Mediated Therapy with virus-negative inflammatory cardiomyopathy) study37
was the first randomized, placebo-controlled trial in which
Controversy continues about the immune mediated therapy all EMB were studied for inflammation by histological and
for myocarditis. In view of the chronic inflammatory immunohistological criteria. Molecular biological analyses
nature of the disease and the effects of the immune were performed in all biopsy specimens to exclude viral
system, immunomodulatory therapy might be beneficial. infection. A significant improvement of LV ejection fraction
However, non-selective therapy has not proved useful. One and a decrease in LV dimensions resulted from immuno
of the largest randomized, controlled treatment trials, the suppressive therapy with prednisone and azathioprine.37
Myocarditis Treatment Trial35 failed to show the benefit Patients with fulminant viral myocarditis and hemodynamic
from immunosuppressive therapy additional to heart compromise at presentation are more likely to experience
failure therapy. There was neither a difference in mortality complete recovery than patients with acute myocarditis,81 if
nor an improvement of LV ejection fraction after 1 year of aggressive pharmacological and/or mechanical circulatory
treatment with prednisone and with either azathioprine or support is initiated early during the fulminant phase.38 In
cyclosporine versus placebo. These results might be due to patients with cardiac sarcoidosis or giant cell myocarditis,
a lack of consensus in interpretation of EMB findings. No prognosis depends probably on an early initiated treatment
immunohistology for the detection of inflammatory cells and (immunosuppressive therapy or heart transplantation).39
no molecular biological analyses of EMB were used for the
detection of infectious agents. Device Therapy in Heart Failure
Better efforts are required to distinguish viral from non-
infectious autoimmune forms of the disease in order to guide Device therapy is indicated in symptomatic patients on
appropriate treatment. Molecular biological detection of optimal drug therapy. Mechanical dyssynchrony, defined
cardiotropic viruses can be performed by nested polymerase as non-synchronous contraction between the walls of the
chain reaction (PCR)/real time-PCR from EMB. Finally, LV (intraventricular) or between the ventricular chambers
this contemporary diagnostic repertoire is essential for the (interventricular) impairs systolic function, adversely affects
selection of DCM patients who will likely to benefit from ventricular filling, increases wall stress and worsens mitral
immunosuppression or antiviral interferon (IFN) treatment. regurgitation. Dyssynchrony is defined by widening of
The molecular biological diagnosis of viral genomes comprises QRS complex on the ECG. The indications for cardiac
PCR for the qualitative evaluation, quantitative PCR (qPCR) resynchronization therapy (CRT) are summarized in Table 1.
for the determination of viral loads and sequencing for the This therapy has been shown to restore the coordination
analysis of viral genotypes. Treatment with IFN-beta in and relaxation of the cardiac chambers which results in
patients with myocardial enteroviral or adenoviral persistence favorable cardiac remodeling and improves survival in this
and LV dysfunction showed an elimination of viral genomes population.40 However, up to a third of patients do not have
in all patients and an improvement of LV function in 15 of 22 any clinical benefit with present recommended criteria.
patients.6 In the subsequent placebo-controlled, randomized, These patients could have identifiable reasons for a poor
double-blind, Europe wide multicenter Betaferon in patients response. Thus, their drug doses, compliance to medications
with chronic viral cardiomyopathy study, the treatment with and fluid restriction, underlying arrhythmias, LV lead
Betaferon significantly reduced the viral load (enteroviruses) position, optimization of atrioventricular timings must be
in the myocardium and significant improvement in NYHA reviewed.
class and patient global assessment was seen.36
Table 1
Immunoglobulin Treatment Indications for cardiac resynchronization therapy
The rationale to use immunoglobulin (Ig) in viral myocarditis RT indicated if all 3 criteria (below) are fulfilled.
C
results from their antiviral and immunomodulating effects. LVEF ≤ 35%
In recent onset of myocarditis or DCM, only children with QRS duration of > 120 msec
acute myocarditis showed an improvement of LV function and NYHA II-IV symptoms with optimal medical therapy
survival in the 1st year after treatment. Consider CRT if both criteria given below are fulfilled.
Virus negative inflammatory myocarditis, there is LVEF ≤ 35%
692 evidence that removal of circulating antibodies by immuno NYHA II-IV symptoms with frequent right ventricular pacing
Implantable Cardioverter-defibrillator non-ischemic disease remains problematic. For these reasons, 48
gene-based therapies such as gene therapy, stem-cell therapy
Sudden Cardiac Death (SCD) may occur in nearly 30 and targeted treatments are being investigated.
Dilated Cardiomyopathy
percent of patients with nonischemic dilated cardiomyopathy
(NICM).41 The risk is highest in patients with aborted SCD Stem Cell Therapy
and unexplained syncope. In a meta-analysis of 5 primary
and secondary trials a risk reduction of 31 percent in all cause Interest in the use of stem cell therapy as a treatment for end-
mortality was seen, however as mortality on optimal medical stage DCM has increased during the past decade. Several studies
therapy is as low as 7 percent, this figure translates to 2 percent have documented beneficial effects of stem cell transplantation
per year.42 Moreover, as implantable cardioverter-defibrillator in patients who have depressed left ventricular systolic
(ICD) does not cause any symptomatic improvement, patients dysfunction after myocardial infarction. However, concern has
in NYHA Class IV or with life expectancy of less than 6 grown that this approach might only result in paracrine growth
months are not candidates for the device. Thus, the ICD factor stimulation or improvement in myocardial scaffolding
treatment needs to be individualized. without generation of new myocardium.51,52
Cardiac transplantation is needed in extreme cases. At
Left Ventricular Assist Device present, transplants are reserved for patients with the most
severe disease those needing inotropes and usually mechanical
Studies have found that the left ventricular assist device (LVAD) ventilatory and mechanical device support.
normalises hemodynamics, improves progressive dysfunction
of the heart, improves exercise tolerance and allows patients to Lifestyle Management
become outpatients. On closer look, it was observed that patients
with non-ischemic DCM on optimal doses of ACE inhibitor
Exercise Training
and β-blocker therapy and shorter duration of disease process,
responded favorably to ventricular assist devices. Various Exercise training is recommended as an adjunctive treatment
ventricular assist devices exist at present; some are stationary, in patients with heart failure. HF-ACTION trial controlled
others ambulatory and some are fully implantable. Use of trial investigating outcomes of exercise training) investigated
ventricular assist devices has significantly improved survival of short and long-term outcomes of a supervised exercise
adults and children with DCM with end-stage disease who are program in heart failure and confirmed a decrease in mortality
awaiting heart transplant. The total artificial heart is used for and increase in patient’s sense of well-being in these patients,
destination therapy (use of long-term mechanical circulatory however, in the presence of acute myocarditis one must
support in patients with end stage heart failure, without the abstain from active sport. The duration of abstinence advised
intention of eventual heart transplantation).43,44 by Bethesda Conference Task Force is 6 months.53,54
http://vip.persianss.ir
9 clinical predictors, laboratory data, and medical therapy, is a conduction system disorder. 18 percent of patients less
correlates well with 1-, 2-, and 3-year survival, similar to the than 10 years of age had delayed intracardiac conduction.
Framingham Coronary Heart Disease Risk Model and is able 92 percent of patients presenting at more than 30 years of
Congenital cardiomyopathies
to predict the mode of death in heart failure: pump failure vs age had conduction system disease and 44 percent required
SCD.56 Less information is available on the natural history of pacemaker placement. In early stages, they have an ECG
myocarditis in children. Other clinical risk factors in patients with low amplitude P waves, prolonged PR interval and
with suspected myocarditis are low systolic, diastolic and relatively normal QRS complex.59 Subsequently they
mean arterial blood pressures as well as high heart rate. A develop atrial fibrillation and DCM. A high incidence of
prolonged QRS duration > 120 ms has also been shown to thromboembolic events has been noted in 30 percent these
predict for cardiac death or heart transplantation in patients patients. Presence of conduction system disease indicates
with suspected myocarditis. progressive fibrosis. Meune et al implanted ICDs in 19
patients who had lamin A/C mutations and indications for
Specific Cardiomyopathies pacemaker and found that 42 percent patients received
shocks. As the data are controversial about appropriateness
of shocks.60 Knowledge of patient’s family history of SCD
Peripartum Cardiomyopathy
indicates a low threshold for SCD41 which is associated
Peripartum cardiomyopathy is a disorder, in which initial LV with conduction system disease. The mechanisms that are
systolic dysfunction and symptoms of heart failure develop responsible for the development of this disease, conduction
between the late stages of pregnancy and early postpartum system abnormalities and skeletal myopathy are being
period, typically within 1 month of predelivery and 5 months established.
postdelivery.57 Its causes and pathogenesis are poorly
understood. The disorder is common in some countries and rare Fetal Cardiomyopathy
in others. In most patients with this disorder, molecular markers
of an inflammatory process are identified. Affected women Systolic and diastolic fetal cardiac function have become part
generally present clinically with typical signs and symptoms of the routine evaluation of the fetal heart. In series of neonates
of heart failure; signs of thromboembolism are also frequent. and infants, cardiomyopathy was observed in about 2 to 7
Conventional heart-failure treatment is typically used. Effective percent, but probably during the fetal life the prevalence is higher
treatment reduces mortality rates and increases the number of 6 to 11 percent. The high intrauterine loss, occurring in
women who fully recover LV systolic function. Outcomes for one-third of affected fetuses, likely accounts for these
subsequent pregnancies after peripartum cardiomyopathy are differences. Fetal echocardiography, B and M-mode is the
better for women who have fully recovered heart function main diagnostic tool and it is useful for the therapeutic
compared with those who have persistent LV dysfunction. orientation and to determine the neonatal outcome. A
hemodynamic evaluation can be performed by Doppler
Left Ventricular Non-compaction mode. Cardiomyopathies can be isolated or associated with
other cardiac and non-cardiac malformations. All the studies
Left ventricular non-compaction has been discussed in confirm a great variability of DCM in the fetal age as for the
Chapter 49. anatomical and functional forms, etiology and hemodynamic
impact with different final outcome. Genetic, metabolic,
Familial Dilated Cardiomyopathy infective and cardiac diseases may present with DCM.
Ventricular dysfunction may be progressive in utero and after
Familial dilated cardiomyopathy is now thought to account birth, but possibility of improvement or even normalization
for upto 50 percent of idiopathic dilated cardiomyopathy of the LV. dysfunction is known in all forms of DCM,
(IDC). Most of these cases (>90%) are thought to have idiopathic, postinfective or in non-compaction of LV. The
autosomal dominant inheritance, although X-linked and outcome is worse in presence of fetal hydrops, significant
autosomal recessive forms have been identified. This requires atrioventricular valve regurgitation, for the earlier age at
a sufficient family history to identify at least two first-degree presentation and when diastolic dysfunction is associated
family members with IDC. This is difficult as the disease is with systolic dysfunction. Unfortunately, a poor outcome
variable with age dependent penetrance even within the family. is observed in most, particularly in DCM, with only a few
Although up to 50 percent patients with IDC may have familial therapeutic options available. Detailed evaluation of fetal
DCM (FDC) by history, a genetic test may identify the disease and maternal condition provide prognostic information for
in only 10 percent causes.58 prenatal counselling and may lead to improved outcome.61
Dilated Cardiomyopathy
difficult to ascertain, particularly in children. Arrhythmias form systemic emboli in patients with dilated cardiomyopathy. Br
Heart J. 1989;62:26-9.
an important mode of death. ACE-inhibitors and β-blockers
14. Armstron WF, Ryan T. Feigenbaum’s Echocardiography:
along with diuretics are the mainstay of the therapy. Device
Lippincott Williams and Wilkins; 2010. pp. 9507.
therapy is now useful in symptomatic patients but in end stage 15. Braunwald E. Biomarkers in heart failure. N Engl J Med 2008;
disease, cardiac transplantation is the only option. 358:2148-59.
16. Horwich TB, Patel J, MacLellan WR, Fonarow GC. Car-
The greatest mistake in the treatment of diseases is that diac troponin I is associated with impaired hemodynam-
there are physicians for the body and physicians for the soul, ics, progressive left ventricular dysfunction, and increased
although the two cannot be separated. mortality rates in advanced heart failure. Circulation. 2003;108:
—Plato 833-8.
17. Hudson MP, O’Connor CM, Gattis WA, Tasissa G, Hasselblad
V, Holleman CM, et al. Implications of elevated cardiac tro-
References ponin T in ambulatory patients with heart failure: a prospective
analysis. Am Heart J. 2004;147:546-52.
1. Richardson P, McKenna W, Bristow M, Maisch B, Mautner 18. Logeart D, Thabut G, Jourdain P, Chavelas C, Beyne P,
B, O'Connell J, et al. Report of the 1995 World Health Beauvais F, et al. Predischarge B-type natriuretic peptide
Organization/International Society and Federation of assay for identifying patients at high risk of re-admission after
Cardiology Task Force on the Definition and Classification of decompensated heart failure. J Am Coll Cardiol. 2004;43:635-
cardiomyopathies. Circulation 1996;93:841-2. 41.
2. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, 19. Lambert A, Lapyere AC 3rd, Cooper LT: Current role of Endo
Arnett D, et al. Contemporary definitions and classification of myocardial biopsy in the management of Dilated Cardiomy-
the cardiomyopathies: an American Heart Association Scientific opathy and Myocarditis. Mayo Clin Proc: 2001;76:1030-8.
Statement from the Council on Clinical Cardiology, Heart 20. Ismail TF, Prasad KS, Pennell DJ. Prognostic importance
Failure and Transplantation Committee; Quality of Care and of late gadolinium enhancement cardiovascular magnetic
Outcomes Research and Functional Genomics and Translational resonance in cardiomyopathy. Heart. 2012;98:438-42.
Biology Interdisciplinary Working Groups; and Council on 21. Slavich M, Florian A, Bogaert J. The emerging role of magnetic
Epidemiology and Prevention. Circulation 2006; 113:1807-16. resonance imaging and multidetector computed tomography
3. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, in the diagnosis of dilated cardiomyopathy. Insights Imaging.
Charron P, et al. Classification of the cardiomyopathies: a 2011;2:453-69.
position statement from the European Society Of Cardiology 22. The SOLVD Investigators. Effect of enalapril on survival in
Working Group on Myocardial and Pericardial Diseases. Eur patients with reduced left ventricular ejection fractions and
Heart J 2008;29:270-6. congestive heart failure. N Engl J Med. 1991;325:293-302.
4. Ramani GV, Uber PA, Mehra MR. Chronic Heart Failure: 23. Rogers WJ, Johnstone DE, Yusuf S, Weiner DH, Gallagher P,
Contemporary Diagnosis and Management: Mayo Clin Proc:. Bittner VA, et al. Quality of life among 5,025 patients with
2010;85:180-95. left ventricular dysfunction randomized between placebo and
5. Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, enalapril: the Studies of Left Ventricular Dysfunction. The
Clunie S et al. Incidence, causes, and outcomes of dilated SOLVD Investigators. J Am Coll Cardiol. 1994;23:393-400.
cardiomyopathy in children. JAMA. 2006;296:1867-76. 24. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB,
6. Taylor MR, Carniel E, Mestroni L. Cardiomyopathy, familial Gilbert EM, et al. The effect of carvedilol on morbidity and
dilated. Orphanet J Rare Dis. 2006;1:27. mortality in patients with chronic heart failure. US Carvedilol
7. Mestroni L, Gilbert EM, Lowes BD, Bristow MR: Dilated Heart Failure Study Group. N Engl J Med 1996;334:1349-55.
Cardiomyopathy In Fuster V, Walsh RA, Harrington RA (Eds): 25. Hernandez AF, Hammill BG, O’Connor CM, Schulman
Hurst’s The Heart. The Tata McGraw-Hill Co; 2011. pp. 82. KA, Curtis LH, Fonarow GC. Clinical effectiveness of beta-
8. Jefferies JL, Towbin JA: Dilated cardiomyopathy: Lancet blockers in heart failure: findings from the OPTIMIZE-HF
2010;375:752-762 (Organized Program to Initiate Lifesaving Treatment in
9. Rakar S, Sinagra G, Di Lenarda A, Poletti A, Bussani R, Hospitalized Patients with Heart Failure) Registry. J Am Coll
Silvestri F, et al. Epidemiology of dilated cardiomyopathy. A Cardiol. 2009;53:184-92.
prospective post-mortem study of 5252 necropsies. The Heart 26. Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators.
Muscle Disease Study Group. Eur Heart J. 1997;18:117-23. A randomized trial of the angiotensin-receptor blocker valsartan
10. Wilkinson JD, Landy DC, Colan SD, Towbin JA, Sleeper LA, in chronic heart failure. N Eng J Med. 2001;345:1667-75.
Orav EJ, et al. The Pediatric Cardiomyopathy Registry and 27. Burnier M, Brunner HR. Angiotensin II receptor antagonists.
Heart Failure: Key Results from the First 15 Years. Heart Fail Lancet. 2000;355:637-45.
Clin. 2010;6:401-13. 28. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et
11. Towbin JA, Bowles NE. The failing heart. Nature. 2002;415: al. The effect of spironolactone on morbidity and mortality in
227-233. patients with severe heart failure. Randomized Spironolactone
12. Luk A, Ahn E, Soor GS, Butany J. Dilated Cardiomyopathy: A 695
Evaluation Study Investigators. N Engl J Med. 1999;341:
review: J Clin Path 2008;62:219-225. 709-17.
http://vip.persianss.ir
9 29. Ferdinand KC. Isosorbide dinitrate and hydralazine
hydrochloride: a review of efficacy and safety. Exp Rev
45. Tulner SA, Steendijk P, Klautz RJ, Tops L, Bax JJ, Versteegh
MI, et al. Clinical efficacy of surgical heart failure therapy by
Cardiovasc Ther. 2005;3:993-1001. ventricular restoration and restrictive mitral annuloplasty. J
Congenital cardiomyopathies
30. Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino R Card Fail. 2007;13:178-83.
Jr, Ferdinand K, et al. Combination of isosorbide dinitrate 46. Siminiak T, Hoppe UC, Schofer J, Haude M, Herrman JP,
and hydralazine in blacks with heart failure. N Engl J Med. Vainer J, et al. Effectiveness and safety of percutaneous
2004;351:2049-57. coronary sinus-based mitral valve repair in patients with
31. Digitalis Investigation Group. The effect of digoxin on dilated cardiomyopathy (from the AMADEUS trial). Am J
mortality and morbidity in patients with heart failure.N Engl J Cardiol. 2009;104:565-70.
Med.1997;336:525-33. 47. Schofer J, Siminiak T, Haude M, Herrman JP, Vainer J, Wu JC,
32. Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, Aronow WS, et al. Percutaneous mitral annuloplasty for functional mitral
Rysz J, Banach M. Statins and dilated cardiomyopathy: do we regurgitation: results of the CARILLON Mitral Annuloplasty
have enough data?. Expert Opini Investig Drugs. 2011;20:315- Device European Union Study. Circulation. 2009;120:326-33.
23. 48. Abe T, Fukada J, Morishita K. The Batista procedure: fact,
33. Kopecky SL MD, Litin SC. Clinical Pearls in Cardiology. fiction and its role in the management of heart failure. Heart
Concise review for Physicians. Mayo Clin Proc. 2010;85: Fail Rev. 2001;6:195-9.
473-8. 49. Koyama T, Nishina T, Ono N, Sakakibara Y, Nemoto S, Ikeda
34. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau T, et al. Early and mid-term results of left ventricular volume
R et al. Amiodarone or an implantable cardioverter-defibrillator reduction surgery for dilated cardiomyopathy. J Card Surg.
for congestive heart failure. Sudden Cardiac Death in Heart 2005;20:S39-42.
Failure Trial (SCD-HeFT) Investigators. N Engl J Med. 50. Isomura T. Surgical treatment for heart failure: left ventricular
2005;352:225-37. restoration for cardiomyopathy. Circ J 2009;73 suppl A:A 6-12.
35. Mason JW, O’Connell JB, Herskowitz A, Rose NR, McManus 51. Stamm C, Choi YH, Nasseri B, Hetzer R. A heart full of
BM, Billingham ME, et al. A clinical trial of immunosuppressive stem cells: the spectrum of myocardial progenitor cells in the
therapy for myocarditis. The Myocarditis Treatment Trial postnatal heart. Ther Adv Cardiovasc Dis. 2009;3:215-29.
Investigators. N Engl J Med 1995;333: 269-75. 52. Liu J, Sluijter JP, Goumans MJ, Smits AM, van der Spoel T,
36. Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Nathoe H, et al. Cell therapy for myocardial regeneration. Curr
Yilmaz A et al. Update on myocarditis. J Am Coll Cardiol. Mol Med. 2009;9:287-98.
2012;59:779-92. 53. O’Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper
37. Frustaci A, Russo MA, Chimenti C. Randomized study on the LS, Ellis SJ, et al. Efficacy and safety of exercise training in
efficacy of immunosuppressive therapy in patients with virus- patients with chronic heart failure: HF-ACTION randomized
negative inflammatory cardiomyopathy: the TIMIC study. Eur controlled trial. JAMA. 2009;301:1439-50.
Heart J. 2009;30:1995-2002. 54. Flynn KE, Piña IL, Whellan DJ, Lin L, Blumenthal JA, Ellis
38. McCarthy RE 3rd, Boehmer JP, Hruban RH, Hutchins SJ, et al. Effects of exercise training on health status in patients
GM, Kasper EK, Hare JM, et al. Long-term outcome of with chronic heart failure: HF-ACTION randomized controlled
fulminant myocarditis as compared with acute (nonfulminant) trial. JAMA. 2009;301:1451-9.
myocarditis. N Engl J Med. 2000;342:690-5. 55. Wang H, Parker JD, Newton GE, Floras JS, Mak S, Chiu KL, et
39. Wu LA, Lapyere AC 3rd , Cooper LT. Current Role of al. Influence of obstructive sleep apnea on mortality in patients
Endomyocardial Biopsy in the Management of dilated with heart failure. J Am Coll Cardiol. 2007;49:1625-31.
Cardiomyopathy and Myocarditis. Mayo Clin Proc 2001;76: 56. Mozaffarian D, Anker SK, Anand I, Linker DT, Sullivan MD,
1030-8. Cleland JG, et al. Prediction of mode of death in heart failure:
40. Mullens W, Grimm RA, Verga T, Dresing T, Starling RC, the Seattle Heart Failure Model. Circulation 2007;116:392-8.
Wilkoff BL, et al. Insights from a cardiac resynchronization 57. Hilfiker-Kleiner D, Sliwa K, Drexler H. Peripartum
optimization clinic as part of a heart failure disease management cardiomyopathy: recent insights in its pathophysiology. Trends
program. J Am Coll Cardiol. 2009;53:765-73. Cardiovasc Med. 2008;18:173-179.
41. Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson 58. Mestroni L, Rocco C, Gregori D, Sinagra G, Di Lenarda A,
KP, et al. Prophylactic defibrillator implantation in patients Miocic S, et al. Familial dilated cardiomyopathy: evidence for
with nonischemic dilated cardiomyopathy. N Engl J Med. genetic and phenotypic heterogeneity. Heart Muscle Disease
2004;350:2151-8. Study Group. J Am Coll Cardiol. 1999;34:181-190.
42. Desai AS, Fang JC, Maisel WH, Baughman KL. Implantable 59. Hershberger RE, Hanson E, Jakobs PM, Keegan H, Coates K,
defibrillators for the prevention of mortality in patients with Bousman S et al. Novel lamin A/C mutation in a family with
nonischemic cardiomyopathy: a meta-analysis of randomized dilated cardiomyopathy, prominent conduction system disease,
controlled trials. JAMA. 2004;292:2874-9. and need for permanent pacemaker implantation. Am Heart J.
43. Miller LW, Pagani FD, Russel SD, ohn R, Boyle AJ, Aaronson 2002;144:1081-6.
KD, et al. Use of a continuous-flow device in patients awaiting 60. Meune C, Van Berlo JH, Anselme F, Bonne G, Pinto YM,
heart transplantation. N Engl J Med 2007;357:885-96. Duboc D. Primary prevention of sudden death in patients with
44. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson lamin A/C gene mutations. N Engl J Med. 2006;354: 209-10.
LW, Dembitsky W et al. Long-term mechanical left ventricular 61. Fesslova V, Mongiovì M, Pipitone S, Brankovic J, Villa L.
assistance for end-stage heart failure. N Engl J Med. 2001;345: Features and outcomes in utero and after birth of fetuses with
696
1435-43. myocardial disease. Int J Pediatr. 2010. pp. 628-51.
C hapter
Vijayalakshmi IB
http://vip.persianss.ir
9
Congenital cardiomyopathies
Figure 1: Histopathological examination shows an opened out left ventricle (LV) showing
a markedly trabeculated wall in the middle and apical portions of the ventricle. Note:
Small anterior papillary muscle (APM), poorly formed group of posterior papillary muscle
(PPM) and thickened leathery appearance of anterior leaflet of mitral valve (MV). This
11-year-old boy had been initially diagnosed as a case of rheumatic mitral regurgitation.
Image courtesy: Dr Pradeep Vaideeswar
also in association with other congenital anomalies. Iso- the ventricle during intrauterine development are absent.
lated LVNC is now being recognized with increasing fre- In particular, various forms of semilunar valve obstruction
quency, with various echocardiographic studies reporting or left ventricular outflow tract obstruction have to be ruled
its finding in between 0.05 percent and 0.24 percent.7,8,14-17 out. A similar persistence of non-compacted myocardium is
Ritter et al15 suggested that the incidence is 0.05% in frequently reported in patients with congenital left or right
adults. Pignatelli et al17 from the Texas Children’s Hos- ventricular outflow tract obstruction and is referred to as ‘spongy
pital, reviewed about 50,000 echocardiograms performed myocardium’ or ‘persisting sinusoids’ that communicate with
in over 26,000 patients from 1997 to 2002 and found the coronary arteries.4,21-26 (Figure 2A) By contrast, isolated
36 patients with the isolated form of the malformation. Over ventricular non-compaction is a genetically heterogeneous
this period, the same group diagnosed 344 cases of cardiomy- congenital disorder characterized by a pattern of excessively
opathy, and/of which non-compaction accounted for one-tenth prominent trabecular meshwork and deep intertrabecular
of their cases of cardiomyopathy, a proportion very similar to recesses in the absence of other structural heart diseases.2,27,28
that calculated by Nugent et al in Australia.18 Oechslin et al16 Furthermore, while the persisting sinusoids are enlargements
estimated that isolated LVNC was seen in 0.0014 of all pa- of the coronary vessels (comparable with hemangioma), the
tients referred to their department of echocardiography over a recesses in isolated ventricular non-compaction have no
period of 14 years. Although these contemporary data suggest connection with the coronary circulation.16,23 (Figure 2B). In
that isolated LVNC is an extremely rare form of cardiomyo- fact they are recesses covered by endocardial lining continuous
pathy, we must now accept that it is being recognized with with the ventricular cavity, predisposing to local thrombus
increasing frequency, so we may need to revise our views in formation.
the light of emerging findings.
If ventricular non-compaction does not coexist with other Historical review
cardiovascular pathologies it is called ‘isolated’ ventricular
non-compaction. Although the LV is most commonly Although described as early as 1932, the disorder was
affected (62%), both ventricles can be influenced in some largely unrecognized until the widespread availability of
cases (22–38%).19 In a study, 22 patients (76%) had isolated echocardiography, which has enhanced the detection. It was
ventricular non-compaction and only the LV was affected in Dusek et al4 who provided one of the earliest substantial
all of them.20 descriptions of the entity that probably represents what
698 In isolated ventricular non-compaction, coexisting cardiac we now call ventricular non-compaction. They called
anomalies that cause excessively high pressure exposure of it postnatal persistence of spongy myocardium with an
49
embryonic blood supply. In 1990, Chin and his colleagues G4.5 in one family with severe X-linked LVNC, but without the
described for the first time, morphologically underdeveloped other usual findings of Barth syndrome.34 Pauli et al39 identified
papillary muscles and non-compacted internal myocardial deletion of chromosome 5q in a child with previously repaired
layers, consisting of more than 50 percent of the ventricular congenital heart disease, facial dysmorphism and LVNC. Vatta
wall thickness in their patients.8 Though described as highly et al40 in contrast, have shown that in some patients with either
fatal in early childhood, it has been reported in as old as dilated cardiomyopathy or LVNC, a mutation in Cypher-Zasp,
94-year-old patient.29 a gene encoding a protein i.e. a component of the Z-line in
However ‘non-compacted apex’ in which non-compaction both skeletal and cardiac muscle, may be causal. It may also
of both right and left ventricular apexes and septum is be pertinent that mice lacking FKBP12 have normal skeletal
extremely rare and hardly reported in the literature. Robert muscle, but have a severe dilated cardiomyopathy and a
Anderson says, this is what is known to happen in the ‘chicken condition suggestive of LVNC.41 Clinical studies suggest
heart’, but thus far there has been no evidence to suggest a that LVNC is often familial with predominantly autosomal
similar mechanism in human. Hence, its cause, development, dominant inheritance. It has been linked to mutations in several
clinical course and treatment are fields of further research genes including ZASP,40 a dystrobrevin36 and tafazzin.36,42
in future. The disease can present throughout life with progressive left
ventricular systolic dysfunction.
Genetics Left ventricular non-compaction is certainly known
also to be a part of various syndromes, including the Barth,
Analysis of genetic linkage and mutation has revealed that Noonan, Roifman, Melnick-Needles, Nail-patella, Toriello-
mutations in the gene G4.5, which encodes tafazin and maps to Carey and other uncommon syndromes.14,37,38,43-51 Analysis
chromosome Xq28, are responsible for this myocardial disorder of the Roifman syndrome, characterized by a constellation
in some patients being allelic with Barth syndrome.30-36 In this of antibody deficiency, spondyloepiphyseal dysplasia, facial
regard, G4.5 was initially identified as the gene responsible for dysmorphism, growth retardation and retinal deficiency,
Barth syndrome, an X-linked mitochondrial disease affecting suggested an X-linked pattern of inheritance.45 The etiology
cardiac and skeletal muscle.37,38 These mutations produce a of the Toriello-Carey syndrome, first reported in 1988,
wide phenotypic spectrum of cardiomyopathies, including is unknown, but both X-linked and autosomal recessive
dilated cardiomyopathy, X-linked infantile cardiomyopathy, inheritance have been suggested.46,51 In one case, a 3-year-
and X-linked endocardial fibroelastosis.36 Ichida et al7 found old boy was diagnosed both with the Toriello-Carey syndrome
a mutation in α-dystrophin in some of their patients. Chen and non-compaction, with ultrasound confirming a similar 699
et al. found a novel splice acceptor site mutation of intron 8 of constellation in his unborn sibling.51
http://vip.persianss.ir
9 Embryology the trabecular cardiomyocytes. In support of the cellular
recruitment mechanism, proliferative activity is consistently
The heart is the first organ to form and function in the vertebrate higher within the compact myocardium, as there is a gradient
Congenital cardiomyopathies
embryo.52-61 In this respect, Kirby58 has written—“Heart of decreasing proliferation and increased differentiation
development in all vertebrates from fish to humans follows from the outside of the heart toward the lumen and trabecular
the same general pattern: fusion of the myocardium and side.70-73 This balance of proliferation and differentiation
endocardium in the ventral midline to form a simple tubular is critical to the formation of a functionally competent
heart”. ventricular wall. The hypertrabeculation is likely to be the
Before the fifth week of intrauterine life, the myocardium result of altered regulation in cell proliferation, differentiation
forms a loose network of fibers and sinusoids, which are in and maturation during ventricular wall formation.
continuity with the ventricular cavity. Subsequently, the The fetal heart muscle has a non-compacted appearance
meshwork of fibers become ‘compacted’ and the sinusoids between the 4th and 18th week of development and this
disappear. Pathological arrest of this compaction process leads is important for the nutrition of its cells. The spongy
to the persistence of ventricular hypertrabeculation, so called myocardium is supplied predominately by diffusion of blood
spongy myocardium or LVNC.62 In 1990, Chin et al described in the heart that flows into the spaces between the muscle
a group of eight patients with non-compaction, which was bands. Later and simultaneously with the development of the
not associated with other congenital cardiac abnormalities.8 coronary arteries, which will eventually take over carrying
But recently the childhood form of non-compaction was first blood to the heart muscle, development of the muscle bands
described in association with other congenital abnormalities appears to go backwards. The thickness of the compacted
such as cyanotic congenital heart disease, coronary artery wall and the mass of the heart muscle is then increasing
anomalies and both right and left ventricular outflow tract and hence the pumping function is increasing too. The final
obstruction.4,15,26 Furthermore, it may be associated with appearance is that of a compacted muscular wall of the
neuromuscular abnormalities. Others suggest that it is more heart with minor muscle bands close to its inner surface.
common and that its prognosis is better than expected.63 Therefore ventricular walls of both ventricles in the normal
During mammalian embryonic heart development, heart are made up predominantly of a compacted layer of
the ventricles undergo a series of morphogenetic myocardial fibers set in a matrix of supporting connective
developments.64-66 Ventricular trabeculation and compaction tissue.5 Rana et al in their study on fertilized chicken egg
are two of the many essential steps for generating a state that component ballooning from the initial linear heart
functionally competent ventricular wall.67 Simplistically, tube is destined to become the LV, the ventricular septum
development of the ventricular wall has four distinct stages. and the adjacent trabeculations. Most importantly, their
Stage I, is the formation of single-cell layered myocardium study shows that the RV, in essence, has comparable origins
at an early developmental stage. Following induction via in mammals and birds, allowing direct extrapolation of
adjacent endoderm, lateral mesoderm gives rise to an early findings in birds to mammalian cardiac development.74 It is
tubular heart. The heart at this stage is composed of one cell of interest to note that, in the evolution of the vertebrates,
layer of myocardium and one cell layer of endocardium lining myocardial non-compaction is advantageous and indeed
the lumen.64,68 Stage II, is the formation of a trabeculated and necessary, for the circulatory function of some fish and yet
compact myocardium at the early mid-gestation stage. As the its presence is decidedly disadvantageous for man.23,75,76
myocardium thickens, cardiomyocytes along the inner wall Ventricular non-compaction, a genetically heterogeneous
form sheet-like protrusions into the lumen to give rise to the disorder,77 may affect both ventricles and apical septum,
trabecular myocardium, while the outside layer of myocardium may be associated with many diverse forms of congenital
becomes organized into compact myocardium. Ventricular cardiac malformations. This apical non-compaction entity
trabeculation has been suggested to facilitate oxygen and was detected in the fetus of 24 weeks gestation with
nutrient exchange and to enhance force generation to match muscular ventricular septal defect (VSD) (Figure 3). This
the increasing blood flow in developing embryos.64,67 Stage patient came back to us after delivery and the infant did have
III, myocardial compaction, occurs at the late mid-gestation apical non-compaction along with a large VSD and patent
stage. As development proceeds, the trabecular myocardium ductus arteriosus.
becomes compacted towards the myocardial wall and
contributes to forming a thicker, compact ventricular wall. Clinical Findings
Stage IV, is the formation of a mature and multilayered spiral
myocardium during the late fetal and neonatal stage.66,69 Patients with LVNC may have normal ventricular function,
Following the formation of primitive trabecular ridges hemodynamics and may lead a normal life. Patients may
the myocardium undergoes extensive expansion either by present at any age from infancy to older than 94 years.29
recruitment of cardiomyocytes from the myocardial wall The clinical manifestations may include heart pump failure,
700 into the trabecular ridges or via cellular proliferation within arrhythmias and thromboembolic events.14
Diagnosis 49
The literature shows quantification and diagnosis of LVNC may
Table 1
Diagnostic criteria for left ventricular non-compaction
Author Criteria
Chin et al8 LVNC is defined as a ratio X/Y ≤ 0.5
X = distance from the epicardial surface to the trough of the trabecular recess
Y = distance from the epicardial surface to peak of the trabeculation
These criteria focus on trabeculae at the left ventricular apex on the parasternal short axis and apical views
and on left ventricular free wall thickness at end diastole.
Jenni et al85 1. A two layered structure with a thin compacted layer and a thick non-compacted layer measured in end
systole at the parasternal short axis views. LVNC is defined by a ratio of N/C > 2.
N = non-compacted layer of myocardium.
C = compacted layer of myocardium.
2. Absence of coexisting cardiac structural abnormalities.
3. Numerous excessively prominent trabeculations and deep intratrabecular recesses.
4. Recesses supplied by intraventricular blood on color Doppler.
Stollerberger et al86 1. More than 3 trabeculations protruding from the left ventricular free wall, apical to the papillary muscles,
visible in a single image plane.
2. Intertrabecular spaces perfused from the ventricular cavity visualized on color Doppler imaging.
701
http://vip.persianss.ir
9 their approach. The method proposed originally by Chin et al8 conspicuous is the trabecular recesses that penetrate deep into
evaluates the size of trabeculations in relation to the thickness the ventricles. The echocardiographic pattern is characteristic
of the compacted wall in different echocardiographic views and and diagnostic.87,88 Echocardiography, nonetheless, is less
Congenital cardiomyopathies
at different levels of the LV in end-diastole. In this study to than perfect for the diagnosis of non-compaction, since the
quantify the depth of penetration of the intertrabecular recesses adequacy of the investigation depends very much on the
with two-dimensional echocardiography, X to Y ratio has been experience and knowledge of the investigator. Non-compaction
developed (Figure 4). This ratio quotient is of the distance of the apex and the septum are seen as Swiss cheese appearance
between the epicardial surface and trough of a trabecular (Figure 5).
recess (represented by X) and the distance between epicardial Transthoracic echocardiography (TTE) is also useful in
surface and peak of the trabeculae (represented by Y). LVNC is detecting associated lesions like multiple muscular VSDs
defined when the ratio of X/Y ≤ 0.5. The schematic diagram of and supramitral ring along with non-compaction (Figures 6
diagnostic features of biventricular non-compaction with Swiss and 7). A case of probable apical non-compaction in young
cheese interventricular septum is shown in Figure 4. Jenni and man with biventricular non-compaction associated with
coworkers85 have proposed a method that relies on the detection VSD and having undergone surgery at the age of two years
of the two myocardial layers, non-compact and compact, for coarctation of aorta, who presented with heart failure is
in short-axis views of the LV in end-systole. LVNC, in this reported.89 The evidence of non-compacted myocardium in
instance, is defined by the ratio > 2 between non-compacted to both left and right ventricular apex was made with intracardiac
compacted layers. The third definition, proposed by Stollberger echocardiography performed during the electrophysiologic
et al.86 determines the number of prominent trabeculations study for arrhythmia is reported. This method has allowed the
visible in the apical views of the LV in diastole. diagnosis of non-compaction of the ventricular myocardium
The diagnosis of spongy myocardium is challenging, as it due to its high resolution. Color Doppler showed trabecular
has to be differentiated from muscle bundles. Discrete muscle recesses in communication with the ventricular cavity that
bundles, more than 2 millimeter in diameter, that stand out could not be identified with transthoracic echocardiography.90
against the background of the left ventricular endocardium, has Thromboembolic events have been reported in 21 percent to
been reported in 68 percent of normal hearts and are virtually 38 percent of patients with non-compaction and chest pain in
always two to three or less in number. In contrast, in non- 19 percent.8,15,16 The thrombus can be detected in LV (Figure
compaction, there are numerous prominent trabeculations and 8A) or thrombus could be in RV. One of our patient with
http://vip.persianss.ir
9 Septal affection in left ventricular hypertrabeculation/
non-compaction is a finding, predominantly in children
and adolescents. Patients with septal left ventricular
Congenital cardiomyopathies
Figures 11A to C: A. The picture of delta of Nile river; B. Cardiac magnetic resonance image of both the ventricles showing prominent
muscular trabeculations with deep intertrabecular recesses in the apical portion of septum and ventricles, resembling delta of the river;
C. Transthoracic echocardiography in a “Swiss cheese” interventricular septum which resembles delta of the river. LV = Left ventricle; RV
= Right ventricle.
A B
Figures 12A and B: Transthoracic echocardiography in 4-year-old boy with situs inversus, dextrocardia, bicuspid aortic valve, severe aortic
stenosis shows non-compaction with left ventricular dysfunction (EF 35%). AO = Aorta; LA = Left Atrium; LV = Left ventricle.
is that its intrinsically three-dimensional nature permits the tissue. The abnormal non-compacted myocardium is thickest
assessment of all cardiac segments. Sequences based on the use in the apex. It extends to the atrioventricular junction along
of contrast then allow the assessment of myocardial perfusion the free wall, while the basal one-third of the septum is not
and the evaluation of myocardial fibrosis.100 This modality involved.
also allows visualization of left ventricular thrombus.101,102
Computed tomography, however, is of limited value, because it Differential diagnosis
is not possible to assess regional and global ventricular function
and furthermore, the technique depends on the use of radiation. Once the dilated and hypertrophic variants of cardiomyopathy
The utility of electrographically gated CT, nonetheless should are excluded from consideration, there are relatively few
be investigated. Cine MRI in four-chamber and two-chamber further potential diagnosis for myocardial non-compaction.
views shows an interrupted layer of tissue delineating the It is, of course, necessary to exclude the false diagnosis of
non-compacted layer of myocardium from the left ventricular ‘normal’ left ventricular trabeculations as non-compaction, as
cavity. The trabeculations are seen as fine strands extending we discussed earlier. It is also necessary to distinguish non-
from the compacted myocardium towards the thin layer of compaction from the acquired changes seen in the setting 705
http://vip.persianss.ir
9 of lesions such as pulmonary atresia with intact ventricular non-compaction seem less troubled with severe disturbances
septum. Another potentially misleading condition is the of rhythm.
appearance of layered mural thrombus of the LV simulating Cerebrovascular accidents certainly contribute to co-
Congenital cardiomyopathies
non-compaction.14 It has also been suggested that mycotic morbidity in patients with isolated LVNC, the unusual
invasion of the heart can produce the appearance of abnormal hypertrabeculations not only reducing ventricular
trabeculations,103,104 while rarely an intramyocardial hematoma function, but also creating a nidus for formation of mural
may mimic isolated LVNC.105 The question has also been thrombus.7,8,14-17,98,110-115 It is difficult, however, precisely to
asked as to whether LVNC can be a cardiac manifestation determine the incidence of adverse neurological events. It has
of Fabry disease.106 In this respect, while the appearances of been suggested that patients should at least be placed on a
hypertrophic cardiomyopathy are well-documented in patients protocol of oral anticoagulation once the diagnosis of isolated
with Fabry disease, to the best of our knowledge there is no LVNC is made. Of course, if a patient has sustained and
data supporting unequivocally the association of this inborn unequivocal thromboembolic event, then full anticoagulation
metabolic disorder with LVNC. with low-molecular-weight heparin is advised.7,8,16,17 The
The WHO classification of cardiomyopathies should successful interventions for the associated lesions, which
reconsider, inclusion of isolated ventricular non-compaction could be a ray of hope in these patients with pump failure and
as a distinct cardiomyopathy. This would improve not only the reduce the morbidity and postpone the mortality. The balloon
knowledge, but also the awareness of this disorder and thus, dilatation can be done for critical aortic stenosis and coarctation
facilitate its diagnosis, as even a skilled echocardiographer’s of aorta. In our series of cases of apical non-compaction, two
eye sees better, while knowing what to look for.85 situs inversus dextrocardia patients underwent successful
interventions. One 4 year old boy underwent aortic balloon
outcome valvuloplasty (Figure 12 A and B) and another 8 years old
girl’s mid-muscular VSD was closed with Amplatzer duct
Many of the early clinical reports emphasized the dismal occluder II (Figure 13 A and B). Non-compaction of the
outcomes of patients with isolated LVNC,7,8,14-17,62,85,98, ventricle with associated aorto-left ventricular tunnel closed
107-115 focusing on the egregious nature of the often malignant by Amplatzer duct occluder is reported for the first time in
accompanying arrhythmias. Increasing clinical experience world literature.122 This patient had hemolysis for five days.
has modified to some extent this bleak outlook.17,98 In some Hemolysis probably can be minimized if a custom made
asymptomatic patients, isolated LVNC has been found as an device is used to fit the anatomy of the tunnel. Aorto-right
incidental finding.116,117 In others it has been recognized in the ventricular tunnel in biventricular non-compaction has
sixth and seventh decades of life and beyond. Yet the disorder been closed with Amplatzer duct occluder II.123 Associated
certainly has the potential for a poor outcome. Even for those multiple VSDs can be closed by device to reduce the volume
patients presenting in the first year of life with depressed left overload and pump failure in ventricular non-compaction
ventricular contractility, with some recovery of ventricular (Figures 14 A and B). Surgery in ventricular non-compaction
function, recovery can be transient. with associated lesions carry high risk. Therefore non-surgical
In 27 percent of cases in a study, extracardiac diseases, transcatheter interventions are better options for post surgical
mainly mental and motor retardation were found. The most residual VSDs.
common complaints at admission were due to heart failure
(69%). The mortality rate was 21 percent and death was FUTURE
caused by cardiac failure and sepsis.20
The currently increased awareness of the condition has
MANAGEMENT recently led to frequent reports in the medical literature
of people having the features of non-compaction, but
A variety of medical therapies have been utilized in those the clinical significance of this has to be evaluated with
symptomatic patients with congestive heart failure, including caution. High priority should be given to establishing
cardiac glycosides, diuretics, inhibitors of angiotensin standard nomenclature and diagnostic criteria for future
converting enzyme and afterload reducing agents. In those research.82,124,125 Genetic testing of the most clinically
suspected of having an underlying mitochondrial myopathy, affected individuals, echocardiographic or cardiac MRI
a ‘metabolic’ cocktail has been used.17 Beta-blockers has also screening of all first degree relatives and obtaining family
been used with some success.118 Some patients have needed history for at least three generations, need to be implemented
cardiac transplantation.119 Disturbances of rhythm have in clinical practice, to further understand the influence of
been treated in standard fashion, while some have implanted genetic mechanisms in this disorder. Finally, the clinicians,
defibrillators for severe ventricular arrhythmias recognized as imaging specialists, geneticists and pathologists all need to
predisposing to sudden death.120,121 Surprisingly, patients with contribute their scientific knowledge to define this elusive
706 complex congenital cardiac malformations coexisting with entity called ‘ventricular non-compaction’.126-128
49
A B
Figures 14A and B: A. Left ventricular angiogram in left anterior oblique view illustrates
non-compaction of left ventricle (black arrows), mid-muscular ventricular septal defect (VSD)
opacifying right ventricle; B. 6 × 6 Amplatzer duct occluder II in situ. Left ventricular angiogram in
left anterior oblique view shows no residual VSD in a 8 months old, 5 kilogram infant. LV = Left
ventricle; RV = Right ventricle.
Conclusion perhaps more common in children. The entity has now been
recognized in the fetus and also in the octogenarian, with
Ventricular non-compaction, a genetically heterogeneous many patients presenting or identified in adults. The peculiar
disorder,78 may affect both ventricles, may be isolated or may association of LVNC with many kinds of neuromuscular
be associated with many diverse forms of congenital cardiac disorders is well-established, but the reasons for this
malformations. It has been identified in patients with a variety association have not been clarified. The prognosis for the
of syndromes. When confined to the LV, patients may present symptomatic patient is generally poor, with progression to
like those with idiopathic dilated cardiomyopathy or less chronic cardiac failure and death. Some patients with isolated 707
frequently with restrictive physiology, this latter physiology LVNC will die suddenly due to arrhythmias, thromboembolism
http://vip.persianss.ir
9 and left ventricular dysfunction. The recently recognized cardium: a rarity or missed diagnosis? Circulation. 2002;106:
myocardial malformation with non-compaction of both the E22-E23.
ventricular apex and septum is almost always associated 14. Stöllberger C, Finsterer J. Left ventricular hypertrabeculation/
Congenital cardiomyopathies
with other hemodynamically significant congenital cardiac noncompaction. J Am Soc Echocardiogr. 2004;17:91-100.
malformations, which worsen the pump failure, pre-existing 15. Ritter M, Oechslin E, Sutsch G, et al. Isolated noncompaction
of the myocardium in adults. Mayo Clin Proc. 1997;72:26-31.
with the non-compaction. Non-surgical interventions or
16. Oechslin EN, Attenhofer Jost CH, Rojas JR, et al. Long-
surgical correction of associated lesions though difficult is term follow-up of 34 adults with isolated left ventricular
feasible and can reduce the morbidity and possibly postpone noncompaction: a distinct cardiomyopathy with poor
mortality. Some symptomatic patients may benefit from prognosis. J Am Coll Cardiol. 2000;36:493-500.
orthotopic cardiac transplantation, if medical therapy fails to 17. Pignatelli RH, McMahon CJ, Dreyer WJ, et al. Clinical
stabilize the condition. characterization of left ventricular noncompaction in children:
a relatively common form of cardiomyopathy. Circulation.
Life is short, the art long, opportunity fleeting, experiment 2003;108:2672-8.
treacherous, judgment difficult. 18. Nugent AW, Daubeney PE, Chondros P, et al. The epidemiology
of childhood cardiomyopathy in Australia. N Engl J Med.
—Hippocrates
2003;348:1639-46.
19. Ulusoy RE, Ku¨c¸u¨karslan N, Kırılmaz A, et al. Noncompaction
References of ventricular myocardium involving both ventricles. Eur J
Echocardiogr. 2006;7:457-60.
1. Junga G, Kneifel S, Von Smekal A, et al. Myocardial ischaemia 20. Ozgur S, Senocak F, Arman Orun U, et al. Ventricular non-
in children with isolated ventricular non-compaction. Eur compaction in children: clinical characteristics and course.
Heart J. 1999;20:910-6. Interact Cardiovasc Thorac Surg. 2011;12(3):370-3.
2. Jenni R, Goebel N, Tartini R, et al. Persisting myocardial 21. Grant RT. An unsusual anomaly of the coronary vessels in the
sinusoids of both ventricles as an isolated anomaly: malformed heart of a child. Heart. 1926;13:273-83.
echocardiographic, angiographic and pathologic anatomical 22. Bellet S, Gouley BA. Congenital heart disease with multiple
findings. Cardiovasc Intervent Radiol. 1986;9:127-31. cardiac anomalies: report of a case showing aortic atresia,
3. Budde BS, Binner P, Waldmuller S, et al. Noncompaction fibrous scar in myocardium and embryonal sinusoidal remains.
of the ventricular myocardium is associated with a de novo Am J Med Sci. 1932;183:458-65.
mutation in the beta-myosin heavy chain gene. PLoS One. 23. Angelini A, Melacini P, Barbero F, et al. Evolutionary
2007;2(12):e1362. persistence of spongy myocardium in humans. Circulation.
4. Dusek J, Ostadal B, Duskova M. Postnatal persistence of 1999;99:2475.
spongy myocardium with embryogenic blood supply. Arch 24. Davignon AL, DuShane JW, Kinacaid OW, et al. Pulmonary
Pathol. 1975;99:312-7. atresia with intact ventricular septum: report of two cases
5. Anderson RH. Anatomy. In: Anderson RH, Baker E, Macartney studied by selective angiocardiography and right heart
F, Rigby ML, Shinebourne EA, Tynan M (Eds). Pediatric catheterization. Am Heart J. 1963;62:690-7.
Cardiology, 2nd edn. Churchill Livingstone, London. 2002. pp. 25. Elliot LP, Adams PJ, Edwards JE. Pulmonary atresia with
37-55. intact ventricular septum. Br Heart J. 1963;25:489-501.
6. Richardson P, McKenna W, Bristow M, et al. Report of the 26. Lauer RM, Fink RM, Petry EL, et al. Angiographic
1995 World Health Organization/International Society and demonstration of intramyocardial sinusoids in pulmonary-
Federation of Cardiology task force on the definition and clas- valve atresia with intact ventricular septum and hypoplastic
sification of cardiomyopathies. Circulation. 1995;93:841-2. right ventricle. N Engl J Med. 1964;271:68-72.
7. Ichida F, Hamamichi Y, Miyawaki T, et al. Clinical features of 27. Gerull B, Sasse-Klaassen S, Oechslin E, et al. Isolated
isolated noncompaction of the ventricular myocardium: long- ventricular noncompaction of the myocardium is a genetically
term clinical course, hemodynamic properties, and genetic heterogeneous disorder.[abstract] Circulation. 1999;100:I-818.
background. J Am Coll Cardiol. 1999;34:233-40. 28. Tsang JC, Chiu RC. The phantom of “myocardial sinusoids”: a
8. Chin TK, Perloff JK, Williams RG, et al. Isolated historical reappraisal. Ann Thorac Surg. 1995;60:1831-35.
noncompaction of left ventricular myocardium: a study of 29. Sato Y, Matsumoto N, Matsuo S, et al. Isolated noncompaction
eight cases. Circulation. 1990;82:507-13. of the ventricular myocardium in a 94-year-old patient:
9. Sarma RJ, Chana A, Elkayam U. Left Ventricular Noncompac- depiction at echocardiography and magnetic resonance
tion . Prog Cardiovasc Dis. 2010;52:264-73. imaging. Int J Cardiol. 2007;119:e32-e34.
10. Wong SP, Oldfield M, Ko AP, et al. Ventricular non-compaction: 30. Gedeon AK, Wilson MJ, Colley AC, et al. X linked fatal
a rare cause of heart failure. Intern Med J. 2003;33:262-3. infantile cardiomyopathy maps to Xq28 and is possibly allelic
11. Baumhakel M, Kindermann I, Kindermann M, et al. Isolated to Barth syndrome. J Med Genet. 1995;32:383-8.
noncompaction of ventricular myocardium syndrome: a rare 31. Matsuda M, Tsukahara M, Kondoh O, et al. Familial isolated
structural heart disease. Dtsch Med Wochenschr. 2003;128:562-7. noncompaction of ventricular myocardium. J Hum Genet.
12. Buonanno C, Variola A, Dander B, et al. Isolated noncompaction 1999;44:126-8.
of the myocardium – an exceedingly rare cardiomyopathy: a 32. Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-
case report. Ital Heart J. 2000;1:301-5. linked noncompaction of the left ventricular myocardium:
708 13. McCrohon JA, Richmond DR, Pennell DJ, et al. Images in prenatal diagnosis and pathologic analysis of affected
cardiovascular medicine. Isolated noncompaction of the myo- individuals. Am J Med Genet. 1997;72:257-65.
33. Bione S, D’Adamo P, Maestrini E, et al. A novel X-linked
gene, G4.5 is responsible for Barth syndrome. Nat Genet.
52. Icardo JM. Developmental biology of the vertebrate heart. J
Exp Zool. 1996;275:144-61.
49
1996;12:385-9. 53. Sanchez-Quintana D, Garcia-Martinez V, Climent V, et al.
http://vip.persianss.ir
9 74. Rana MS, Horsten NC, Tesink-Taekema S, et al. Trabeculated
right ventricular free wall in the chicken heart forms by
92. Chung T, Yiannikas J, Lee LC, et al. Isolated noncompaction
involving the left ventricular apex in adults. Am J Cardiol.
ventricularization of the myocardium initially forming the 2004;94:1214-6.
Congenital cardiomyopathies
outflow tract. Circ Res. 2007;100:1000-7. 93. Corrado G, Santarone M, Miglierina E, et al. Isolated
75. Victor S, Nayak VM, Rajasingh R. Evolution of the ventricles. noncompaction of the ventricular myocardium: a study in an
Tex Heart Inst J. 1999; 26:168-75. adult male and literature review. Ital Heart J. 2000;1:372-5.
76. Steiner I, Hrubecky J, Pleskot J, et al. Persistence of spongy 94. Koo BK, Choi D, Ha JW, et al. Isolated noncompaction of
myocardium with embryonic blood supply in an adult. the ventricular myocardium: contrast echocardiographic
Cardiovasc Pathol. 1996;5:47-53. findings and review of the literature. Echocardiography.
77. Petersen SE, Selvanayagam JB, Weismann F, et al. Left ventri 2002;19:153-6.
cular non-compaction: insights from cardiovascular magentic 95. Korcyk D, Edwards CC, Armstrong G, et al. Cardiac-enhanced
resonance imaging. J Am Col Cardiol. 2005;46:101-5. cardiac magnetic resonance in a patient with familial isolated
78. Wald RM, Veldtman GR, Golding F, et al. Determinants of ventricular non-compaction. J Cardiovasc Magn Reson. 2004;
outcome in isolated ventricular noncompaction in childhood. 6:569-76.
Am J Cardiol 2004;94:1581-4. 96. Weiss F, Habermann CR, Lilje C, et al. MRI in the diagnosis of
79. Digilio MC, Marino B, Bevilacqua M, et al. Genetic non-compacted ventricular myocardium (NCVM) compared to
heterogeneity of isolated noncompaction of the left ventricular echocardiography. Rofo. 2003;175:1214-9.
myocardium. Am J Med Genet. 1999;85:90-1. 97. Chung T, Yiannikas J, Lee LC, et al. Isolated noncompaction
80. Freedom RM, Yoo SJ, Perrin D, et al. The morphological involving the left ventricular apex in adults. Am J Cardiol.
spectrum of ventricular noncompaction. Cardiol Young. 2004 1;94:1214-6.
2005;15:345-64. 98. Ali SKM, Godman MJ. The variable clinical presentation and
81. Ramaraj R, Sorrell VL, Marcus F, et al. Recently defined cardio outcomes for noncompaction of the ventricular myocardium
myopathies: a clinician’s update. Am J Med. 2008;121:674-81. in infants and children, and under-diagnosed cardiomyopathy.
82. Kohli S, Pantazis AA, Shah JS, et al. Diagnosis of left- Cardiol Young. 2004;14:409-16.
ventricular non-compaction in patients with left-ventricular 99. Hamamichi Y, Ichida F, Hashimoto I, et al. Isolated
systolic dysfunction: time for a reappraisal of diagnostic noncompaction of the ventricular myocardium: ultrafast
criteria? Eur Heart J. 2008;29:89-95. computed tomography and magnetic resonance imaging. Int J
83. Frischknecht B, Attenhofer Jost CH, Oechslin EN, et al. Valida- Card Imaging. 2001;17:305-14.
tion of noncompaction criteria in dilated cardiomyopathy, and 100. Gebker R, Paetsch I, Wahl A, et al. Ventricular non-compaction.
valvular and hypertensive heart disease. J Am Soc Echocardi- Eur Heart J. 2004;25: Cover Image.
ogr. 2005;18:865-72. 101. Barkhausen J, Hunold P, Eggebrecht H, et al. Detection and
84. Tamborini G, Pepi M, Celeste F, et al. Incidence and characterization of intracardiac thrombi on MR imaging. Am J
characteristics of left ventricular false tendons and trabeculations Roentgenol. 2002;179:1539-44.
in the normal and pathologic heart by second harmonic 102. Petersen SE, Timperley J, Neubauer S. Left ventricular thrombi
echocardiography. J Am Soc Echocardiogr. 2004;17:367-74. in a patient with left ventricular non-compaction – visualisation
85. Jenni R, Oechslin EN, Attenhofer Jost C, et al. Echocardiographic of the rationale for anticoagulation. Heart. 2005;91:e4.
and pathoanatomical characteristics of isolated left ventricular 103. Stöllberger C, Preiser J, Finsterer J. Histological detection
noncompaction: a step towards classification as a distinct of intramyocardial abscesses in Candida sepsis mimicking
cardiomyopathy. Heart. 2001; 86:666-71. left ventricular noncompaction/hypertrabeculation on echo
86. Stollberger C, Finsterer J, Blazek G. Left ventricular cardiography. Mycoses. 2004;47:72-5.
hypertrabeculation, noncompaction and association with 104. Stöllberger C, Preiser J, Finsterer J. Candida sepsis with
additional cardiac abnormalities and neuromuscular disorders. intramyocardial abscesses mimicking left ventricular
Am J Cardiol. 2002;90:899-902. noncompaction. Eur J Echocardiogr. 2004;5:76-8.
87. Vijayalakshmi IB, Sumangala BV, Chitra N. Echo in aorto- 105. Stöllberger C, Finsterer J, Waldenberger FR, et al.
ventricular tunnel with non-compaction of Ieft ventricle. Journal Intramyocardial hematoma mimicking abnormal left ventricular
of the Indian Academy of Echocardiography. 2001;7: 238. trabeculation. J Am Soc Echocardiogr. 2001;14: 1030-2.
88. Vijayalakshmi IB. ‘Role of Echocardiography in Rarest 106. Stöllberger C, Finsterer J, Voigtlander T, et al. Is left ventricular
Congenital Heart Disease’ in Journal of Indian Academy of hypertrabeculation/noncompaction a cardiac manifestation of
Echocardiography. 2003;7:509-12. Fabry’s disease? Z Kardiol. 2003;92:966-9.
89. Tatu-Chitoiu A, Bradisteanu S. A rare case of biventricular 107. Jenni R, Rojas J, Oechslin E. Isolated noncompaction of the
non-compaction associated with ventricular septal defect and myocardium. N Engl J Med. 1999;340:966-7.
descendent aortic stenosis in a young man. Eur J Echocardiogr. 108. Weiford BC, Subbarao VD, Mulhern KM. Noncompaction of
2008;9:306-8. the ventricular myocardium. Circulation. 2004;109:2965-71.
90. Ficili S, Pandozi C, Galeazzi M, et al. Noncompacted 109. Oechslin E, Jenni R. Guest editorial. Isolated left ventricular
ventricular myocardium: characterization by intracardiac echo. non-compaction: increasing recognition of the distinct, yet
J Cardiovasc Med (Hagerstown). 2011;12:294-6. “unclassified” cardiomyopathy. Eur J Echocardiogr. 2002;3:
91. Moon JC, Fisher NG, McKenna WJ, et al. Detection of apical 250-51.
hypertrophic cardiomyopathy by cardiovascular magnetic 110. Halbertsma FJ, van’t Hek LGEM, Daniels O. Spongy
resonance in patients with non-diagnostic echocardiography. cardiomyopathy in a neonate. Cardiol Young. 2001;11:458-
710
Heart. 2004;90:645-9. 60.
111. Neudorf UE, Hussein A, Trowitzsch E, et al. Clinical features
of isolated noncompaction of the myocardium in children.
120. Celiker A, Kafali G, Dogan R. Cardioverter defibrillator
implantation in a child with isolated noncompaction of the
49
Cardiol Young. 2001;11:439-42. ventricular myocardium and ventricular fibrillation. Pacing
711
http://vip.persianss.ir
C hapter
50 Restrictive Cardiomyopathy
restrictive cardiomyopathy
Electrocardiography abnormalities are seen in 80 percent cases, atrial fibrillation
74 percent, intraventricular conduction delay (19%) and the
Electrocardiography (ECG) is abnormal in 98 percent of the ECG is only rarely normal (2%). Atrioventricular block or
patients. The ECG findings corroborate with the enlargement a tachybrady syndrome requiring pacemaker implantation
or hypertrophy of the particular chambers. It usually shows suggests RCM due to neuromuscular disorders such as
evidence of atrial enlargement. Criteria for ventricular hyper desminopathy, myofibrillar myopathy, distal myopathy with
trophy may be seen. Repolarization abnormalities especially rimmed vacuole, chloroquine myopathy or an unspecified
notched and biphasic T waves, obliquely elevated and late myopathy. Familial RCM has been associated with
peaking ST segments, which may prolong the QT interval atrioventricular blocks.8
are seen especially in children. Amyloidosis is a contrasting
example with low voltage ECG seen in all the leads. Blood Test
Peripheral blood eosinophilia may indicate hypereosinophilic
syndrome and Churg-Strauss syndrome. The anemia and
thrombocytopenia may indicate Gaucher disease; serum
electrolytes, hepatic enzymes and renal function tests
detect hepatic or renal dysfunction. Elevated serum muscle
enzymes may indicate neuromuscular disorders; serum
and urine protein analysis may reveal gammopathies
(amyloidosis, Fabry disease) and thyroid function tests for
hypothyroidism (POEMS {polyneuropathy, organomegaly,
endocrinopathy monoclonal gammopathy, skin changes,
mitochondrial myopathy) as hypothyroidism is seen in both
these conditions.
Brain natriuretic peptide (BNP) is a neurohormone
secreted in response to myocardial stretch. Plasma BNP
levels are increased in RCM and are useful for differentiating
it from constrictive pericarditis (especially idiopathic) in
Figure 1: Chest X-ray posteroanterior view shows cardiomegaly,
which they remain normal. It is also a useful prognostic
double shadow due to right atrial (RA) enlargement and pericardial marker as it increases with right heart failure.9
effusion (PE) beyond the RA and left ventricle (LV) border (arrows)
713
Figure 2: Electrocardiogram showing sinus rhythm, biventricular hypertrophy, prolonged QTc, biphasic T wave in chest leads
http://vip.persianss.ir
9
Congenital cardiomyopathies
A B
Figure 3A and B: Transthoracic echocardiography with color Doppler shows left ventricular hypertrophy secondary to amyloidosis in a 2-year-
old child. Aortic valve is normal; B. Parasternal long-axis in 5 years old restrictive cardiomyopathy patient shows large pericardial effusion
Echocardiography
Echocardiographic examination includes M-mode assessment,
2D echo examination, pulse Doppler assessment of mitral,
tricuspid, pulmonary venous and hepatic flows, tissue
Doppler imaging and color M-mode examination. The
findings depend upon the involvement of left/right or both
ventricles and associated pericardial effusion (Figures 3A
and B).
M-mode Echo
Various abnormalities of septal motion, left ventricular
(LV) posterior wall and right ventricular (RV) anterior
wall have been described. Exaggerated movement of the
interventricular septum (IVS) with sharp sudden cessation
of the movement in early diastole, exaggerated thickening
of the posterior wall in late diastole have been described.
The compromise of diastolic filling is manifested by a larger
Figure 4: Apical four-chamber view showing biatrial enlargement
amplitude of the mitral opening at the beginning of diastole
which then remains flat during the rest of diastole. Right
ventricular endomyocardial fibrosis has been associated with
paradoxical septal motion, exaggerated RV anterior wall Doppler
motion as well as increased dimensions of the right ventricle Mitral and tricuspid regurgitation (TR) is often seen
and right ventricular outflow tract. (Figure 6A). This may be due to affliction of the valves by the
disease process itself as well as there may be secondary TR due to
2D Echo pulmonary hypertension (Figure 6B). The flow through the mitral
and tricuspid valves, depending on which ventricle is damaged,
Systolic function is normal till late stages of the disease. presents as practically forming one peak in protodiastole (the
Ventricular volumes are normal. There may be increased E wave) with an acute reduction in declaration time (DT < 160
wall thickness and a characteristic speckled appearance is ms) and a short isovolumic relaxation time (IVRT < 70 ms)
seen in certain infiltrative disorders. Biatrial enlargement is (Figure 7), followed by a greatly reduced A wave (E/A ratio of
ubiquitous in this disease state (Figure 4), along with dilated mitral inflow > 2.0) (Figure 8). This indicates a pattern of rapid
non-collapsing inferior vena cava (Figure 5), hepatic veins inflow immediately after valve opening followed by an abrupt
714 and pulmonary veins. cessation due to reduction in distensibility.
There is no respiratory variation in the filling patterns. 50
Concurrent with abnormalities of mitral valve inflow,
pulmonary vein flow may reveal blunted systolic forward flow.
restrictive cardiomyopathy
The systolic/diastolic (S/D) ratio of pulmonary venous flow is
less than 1 (Figure 9) and the atrial reversal in accentuated.
Mid-diastolic reversal of flow across mitral and/or tricuspid
valves, diastolic MR, is more common with RCM.
Tissue Doppler and color M-mode imaging are less
preload dependent echocardiographic measures of diastolic
dysfunction.
Figure 5: Dilated inferior vena cava (IVC) with no respiratory Figure 8: Pulse wave Doppler at mitral valve level showing tall E
variation (IVC Plethora) wave, E/A ratio is > 2:1, DT < 150 msec
A B
Figures 6A and B: A. Transthoracic echocardiography in an 11-year-old girl of restrictive cardiomyopathy in apical four-chamber view shows 715
small ventricles (RV and LV) large atria (RA and LA), color Doppler shows severe tricuspid regurgitation; B. Color Doppler showing the presence
of tricuspid regurgitation and continuous wave Doppler at tricuspid valve demonstrating pulmonary hypertension. LA = Left atrium; LV = Left
ventricle; RA = Right atrium; RV = Right ventricle.
http://vip.persianss.ir
9
Congenital cardiomyopathies
Figure 9: Pulse wave Doppler at pulmonary vein Figure 11: Color M-mode: Doppler flow propagation velocity (Vp)
showing systolic (S), diastolic (D) waves (D > S) is decreased (Vp < 45 cm/s)
Figure 10: Tissue Doppler: Mitral annular E′ velocity < 10 cm/sec Figure 12: (1) Dip and plateau, ‘Square-Root Sign’; Elevated left
ventricular end diastolic pressure (LVEDP) and right ventricular
end diastolic pressure (RVEDP), LVEDP > 8 mm Hg (2) RVEDP <
1/3rd of right ventricular systolic pressure.
Color M-mode is also useful in RCM. 2 slopes can be less than 1/3rd of the RV systolic pressure (Figure 12). The
measured. One is the slope of transition from color to no early dip, rapid rise, and abrupt plateau gives rise to a ‘square
color as measured from tip of mitral leaflets to apex of LV and root’ sign, similar to constrictive pericarditis. The ventricular
second is the slope of the first aliasing velocity from the tip of diastolic pressure rise may be followed by a more sustained
the mitral leaflets to a position 4 cm distal into the LV(Vp). In rise, a mid-diastolic ventricular pressure rather than a true
RCM, Vp is less than 4 cm/s (Figure 11). plateau. This dip and plateau in the diastolic pressure waveform
Restrictive cardiomyopathy is often a global process is represented by a rapid Y descent followed by a rapid rise and
and similar pathology can be noted in the right ventricle, plateau in the atrial pressure tracing (Figure 13). The descent
including varying degrees of hypertrophy and infiltration and of V wave becomes more prominent in inspiration. A higher
abnormalities of tricuspid inflow and hepatic vein flow as seen LV than RV filling pressure (> 6 mm Hg) strongly favors the
on the left side.10 diagnosis of restrictive cardiomyopathy.1,11
restrictive cardiomyopathy
blockers are used by some because of their potential benefit,
but improvement in ventricular compliance has not been seen.
Beta-blockers are useful in the early stages. They control the
ventricular response in atrial fibrillation. As they increase
the diastolic filling period and hence the stroke volume.
ACE inhibitors and AT1 receptor blockers (angiotensinogen
II blockers) decrease LV mass in hypertension and have
been shown to be useful in experimental studies. They may
also induce hypotension and renal failure. AT1 receptor
blockers can improve exercise performance in patients with
Figure 13: Right atrial pressure tracing showing a rapid Y descent diastolic dysfunction and a hypertensive response to exercise.
Anticoagulation should be considered because of significant
risk of thromboembolic complications. Therapies directed
determines the type of amyloid. In idiopathic RCM, at specific forms of this condition include chelation therapy,
endomyocardial biopsy demonstrates interstitial fibrosis. phlebotomy, bone marrow transplantation, salt restriction and
Immunofluorescent straining, immunohistochemical studies implantable cardioverter defibrillator placement. In children,
and electron-microscopy may be needed for the diagnosis. RCM is primarily idiopathic and transplantation is the
In storage disorders like Gaucher and Fabry disease, EMBx treatment of choice. This is often required within 4 years of
can be diagnostic. Although not required for diagnosis in diagnosis.
hemochromatosis, it may be required to monitor the response
to therapy.12 Specific Cardiomyopathies
http://vip.persianss.ir
9 Angiography Cardiac Amyloidosis
Characteristic obliteration of the apex of the involved This is the prototype of infiltrative heart disease with
Congenital cardiomyopathies
ventricle with varying degrees of atrioventricular valve increased wall thickness. Amyloidosis is a systemic disorder
regurgitation is seen in all patients with left or biventricular characterized by interstitial deposition of linear, rigid, non-
EMF. Endomyocardial biopsy showed fibrous thickening branching, amyloid protein fibrils in multiple organs (e.g.
of the endocardium made up of collagen without classic heart, liver, kidney, nerve). However, absence of extracardiac
fibers. amyloid does not exclude the presence of amyloid heart disease
Treatment: Endarterectomy with atrioventricular valve Currently, 5 subtypes of amyloidosis have been recognized.
replacement of the diseased ventricle has been done with Cardiac involvement is common in all types of amyloidosis
mixed outcome. Cavopulmonary connection has been done in and is the most frequent cause of morbidity and mortality.
some patients.13
Clinical Features
Idiopathic Hypereosinophilic Syndrome
Amyloid deposits can be interstitial and widespread causing
Idiopathic hypereosinophilic syndrome is characterized by RCM, or localized to:
prolonged overproduction of eosinophils of unknown cause i. Conduction tissues resulting in heart block or ventricular
in addition to specific organ damage due to eosinophil derived arrhythmias.
protein toxicity. Its prognosis is correlated with development ii. Cardiac valves causing valvular regurgitation.
of restrictive cardiomyopathy. iii. Pericardium producing constriction.
Usually a disease affecting men of temperate climate and iv. Coronary arteries causing ischemia and
the diagnostic criteria for this disease are: v. Pulmonary vasculature causing pulmonary hypertension.
1. Blood eosinophila of 1,500/uL (1.5 × 10.9/L) or higher Diagnostic studies: The cardiac silhouette can be normal
lasting more than 6 months. or enlarged on the chest X-ray.
2. No parasitic, allergic or known cause of eosinophilia. Electrocardiography (ECG) typically shows decreased
3. Signs or symptoms of cardiac, hematological, pulmonary, voltage, a pseudoinfarction pattern and conduction distur-
neurologic and cutaneous involvement. bances predominate the clinical course.
Cardiac involvement has 3 phases: M-mode echo reveals symmetrical wall thickness
i. Endocardial damage and eosionophilic infiltration of involving the RV and LV, a small or normal LV cavity, variable
the myocardium. (often depressed) systolic function, left atrial enlargement
ii. Thrombosis of damaged endocardium. and small pericardial effusion. 2D Echo findings include
iii. Progressive fibrosis and scarring of the endocardium thickening of the ventricular myocardium with a speckled
leading to RCM. appearance, the interatrial septum and the valves. LV wall
Because this is an eosinophil mediated damage, aim is thickness is an important prognostic variable. In one study
to reduce peripheral blood eosinophila and reduce cardiac patients with biopsy proven amyloidosis and wall thickness
infiltration. Corticosteroids and hydroxyurea are widely of greater than 15 mm had a median survival of 0.4 years
used to reduce eosinophil count and have improved whereas those with wall thickness less than 12 mm had a
survival in hypereosinophilic syndrome. In some patients survival of 2.4 years. Doppler characteristics of restrictive
where a favorable response is not seen with these drugs, physiology are DT less than 150 msec and an increased
interferon alpha has been used to reduce the eosinophil E/A transmitral ratio, which are strong predictors of cardiac
count, but reduction of organ damage still remains death.17
controversial. Case reports of high doses of interferon- The infiltrative pathology associated with amyloidosis
alpha causing a definite improvement in the disease are can be detected by tissue characterization using magnetic
present. 14 resonance imaging (MRI). In a recent study, qualitative
global and subendocardial enhancement of the myocardium
Churg-Strauss Syndrome associated with faster gadolinium clearance from the blood
pool was higher in patients with cardiac amyloidosis than
This is primarily a disease of young women with a history of hypertensive controls. Treatment is often unrewarding.18
allergic rhinitis and bronchial asthma. The presence of four Immunosuppressive therapy with melphalan and prednisolone
of the following six criteria provides a diagnostic sensitivity is the established treatment regimen for primary amyloidosis.
of 85 percent-asthma, eosinophilia greater than 10 percent Autologous stem cell infusion reduces the monoclonal
of white blood cells (WBC) differential count; mono or gammopathy, but has little effect on existing infiltrative
polyneuropathy; non-fixed pulmonary infiltrate on chest amyloid deposits. Orthotopic cardiac transplantation is
718 X-ray; paranasal sinus abnormality; biopsy containing a blood generally not recommended because of systemic nature of the
vessel with extravascular eosinophils.15,16 disease and possibility of recurrence in the transplant.19
Hemochromatosis familial. Familial phenotypes may include an associated skeletal 50
myopathy with or without conduction abnormalities. A proper
It represents an iron overload disorder or iron storage disease family history should be taken and a genetic screening should
restrictive cardiomyopathy
characterized by accumulation of excessive iron within the be done. Children may present with reactive airway disease,
cells of various internal organs. It may result from a genetic recurrent respiratory infections, breathlessness on exertion, or
defect (hereditary hemochromatosis) or from secondary causes more ominously with palpitations, syncope or sudden death.
(e.g. multiple blood transfusions as in thalassemia major Most of these are manifestations are of increased left-sided
(ineffective erythropoiesis). Iron accumulates in the heart, filling pressures and decreased myocardial reserve. Exercise
pancreas, skin, liver, anterior pituitary, gonads. The myocardial stress testing, Holter monitoring and serial BNP measurements
iron deposition usually produces dilated cardiomyopathy, but can may be useful to monitor the disease progression. Presence of
produce RCM, congestive heart failure, conduction abnormalities LVS3/LVS4 is a ubiquitous finding on physical examination.
like supraventricular and ventricular arrhythmias occur in one- ECG is universally abnormal with biatrial enlargement and
third of patients. Bronze diabetes, hepatic dysfunction are non-specific ST-T changes. Echocardiography will show
commonly associated. Echocardiography may show granular diagnostic features of RCM.23
sparkling, atrial enlargement, but these are not specific. Ultrasonic
analysis of integrated backscatter has been used experimentally Natural History
to detect changes in echocardiographic reflectivity of the
myocardium with iron deposits. Computed tomography (CT) This is a progressive disease with a mortality rate of 50 percent
and MRI can demonstrate subclinical cardiac involvement and in 2 years from diagnosis.24,25 Children with RCM should be
tissue characterization can be possible with MRI. Liver biopsy is followed closely for progression of pulmonary hypertension.
the definitive test for iron overload. Endomyocardial biopsy can Those with elevated but reversible pulmonary hypertension are
be confirmatory and reveals stainable iron in the heart. It is more at an urgent need for cardiac transplant, while those with mildly
useful to monitor the therapy. elevated, pulmonary artery pressures may remain stable for
Repeated phlebotomy is recommended for primary years and may not require urgent listing for transplant. Children
hemochromatosis and chelating agent desferrioxamine is presenting with chest pain and syncope and ECG or Holter
beneficial in secondary hemochromatosis. Combinations evidence of ischemia are at risk of sudden cardiac death. The
with oral active chelator deferiprone have been successful use of beta blocker, implantable cardioverter defibrillator and
in Europe. Deferasirox is a novel, orally active agent with urgent listing of cardiac transplant is indicated for these patients.
a single oral dosing. An extensive clinical trial has shown
its efficacy in adults and children and it has a safety profile, Genetic cardiomyopathies in children
which is manageable with regular clinical monitoring.20,21
Cardiac transplantation can be considered in selected cases. These can be classified into four categories, which are not
mutually exclusive.26
Sarcoidosis 1. Inborn errors of metabolism.
2. Malformation syndromes.
Systemic granulomatous disease of unknown etiology. It 3. Storage disease: Pompe disease, Gaucher disease, Fabry
affects young adults between 10 to 40 years of age and presents disease.
with bilateral hilar lymphadenopathy, reticular pulmonary 4. Disorders of energy metabolism that produce suspected
opacities, joints, eyes and skin involvement (erythema cardiotoxic intermediary metabolites.
nodosum). Cardiac involvement occurs in 5 percent and heart
failure can be due to restrictive or dilated cardiomyopathy and Diagnostic Approach
has a progressive course.22
Patients with inborn errors of metabolism often have signs of
Restrictive cardiomyopathy in Children multiple organ dysfunction. The indications to screen for a
biochemical abnormality are onset of acute/chronic encepha-
Restrictive cardiomyopathy in children is far less common lopathy, hypotonia, growth retardation, failure to thrive, etc.
(3–5%) than in adults. Median age of presentation is 9 years Patients with storage diseases who cannot degrade certain
(range 1 month–16 years). The etiology tends to be different in structural components of cells typically develop coarse or
children than adults. While the latter often have RCM associated dysmorphic facial features, organomegaly, short stature or
with amyloidosis or varieties of endocardial fibroelastosis or chronic encephalopathy with a degenerative course. Skeletal
idiopathic or familial; in children, it is exposure to radiation muscle weakness without encephalopathy is usually due to a
or anthracyclines. While in infants evaluation for congenital primary neuromuscular and rarely due to inborn error of me-
metabolic syndromes like Gaucher or Hurler is required, tabolism. Here skeletal muscle weakness precedes the cardiac
many pediatric cases remain idiopathic with upto a third being involvement. 719
http://vip.persianss.ir
9 Metabolic Cardiomyopathies affected, though the onset is in later age (average: 29 years)
and is milder. The disease causes severe renal, cardiac and
Glycogen Storage Diseases cerebrovascular disease. The onset is in childhood and
Congenital cardiomyopathies
Table 1
Difference between restrictive cardiomyopathy and constrictive pericarditis
Clinical history Rare, familial Hx should be ruled out Past Hx of tuberculosis, cardiac surgery, chest
trauma, mediastinal irradiation, epicardial
pacemaker implantation, purulent pericarditis
JVP Raised, with prominent 'a' wave with sharp x and Raised there is prominent rapidly collapsing y
y descents present in early stages and prominent descent combined with a normally prominent x
y descent only will persists in later stages due to descent results in M or W shaped pattern .
atrial dysfunction.
Extra sounds in diastole Loud diastolic filling sound S3 (late), rarely S4, Pericardial knock—high-frequency sound
a low frequency sound
Mitral or tricuspid May have a murmur of mitral or tricuspid Usually a quiet heart
regurgitation insufficiency
Chest X-ray Often have cardiomegaly with biatrial Normal cardiac silhouette, presence of
enlargement, pulmonary vascular redistribution pericardial calcification is pathognomonic
(20–30%), tubercular infiltrates in the lung
fields
Contd...
720
Contd... 50
ECG P waves reflect right/left atrial enlargement. P waves reflect intra-atrial conduction delay.
restrictive cardiomyopathy
Atrioventricular or intraventricular conduction Conduction defects are rare.
defects are not unusual. LVH is more common, RVH and right axis deviation are more
e.g. LVH with T-wave inversion in an infant common.
with endocardial fibroelastosis
Echocardiography
Interventricular septal Abrupt septal movement in early diastole seen Abrupt septal movement (“notch”) in early
movement in diastole only occasionally diastole in most cases. Double component of
septal dip in atrial systole-atrial systolic notch,
additional dip occurs in early to mid diastole
-early diastolic notch.
Pulmonary vein flow Blunted S/D ratio, prominent atrial reversal S/D ratio = 1
No respiratory variation of D wave Prominent inspiratory decrease of S and D
waves.
Tissue Doppler Lateral and diastolic e’ velocities of < 8 cm/s Usually normal (e' >8 cm/s) as myocardium is
have been accepted as a cutoff for RCM. not affected (mitral annular calcification may
W wave may also be reduced to < 5 cm/s reduce sensitivity)
Color M-mode Slow flow propogation (< 45 cm/s) Rapid flow propagation (> 100 cm/s)
Speckle tracking imaging Endocardial dysfunction, hence abnormal Pericardial constraint affects circumferential and
longitudinal mechanics twist mechanics
Myocardial velocity gradients Low due to uniform affection of myocardium High due to preserved endocardial motion but
decreased epicardial motion
Cardiac catheterization
LV and RV diastolic pressure The LV diastolic pressure will exceed RV Diastolic gradients rise equally or even
gradient diastolic pressure by > 5 mm Hg if volume decrease with these stresses
infusion, leg elevation or exercise is done
Dip and plateau End-diastolic pressure often less than one- End-diastolic pressure more than one-third of
waveform in the right third of the systolic pressure the systolic pressure in most cases
ventricular pressure waveform
Cardiac MR Late gadolium enhancement of myocardium May detect thickening, less sensitive to
on MR is suggestive of myocardial infiltrative calcium. Cine MR can detect septal bounce
disease. and real-time Cine MR can detect respiratory
variation seen on echo
http://vip.persianss.ir
9 Conclusion 14. Hassan WM, Fawzy ME, Al Helaly S, et al. Pitfalls in diagnosis
and clinical echocardiographic and hemodynamic findings in
Restrictive cardiomyopathy is a relatively rare form of endomyocardial fibrosis. Chest. 2005;128:3985-92.
Congenital cardiomyopathies
cardiomyopathy in which diastolic function is abnormal 15. Baratta L, Afeltra A, Delfino M, et al. Favorable response to
high-dose interferon Alpha in idiopathic hypereosinophilic
due to the stiff ventricles. The most common cause of RCM
syndrome with restrictive cardiomyopathy. Angiology.
in adults is amyloidosis, whereas in children, the cause is
2002;53:465-70.
unknown. At present, medical therapy remains supportive 16. Alvarez-Sala R, Prados C, Armada E, et al. Congestive cardio-
and appears to be ineffective and the development of myopathy and endobronchial granulomas as manifestations of
pulmonary hypertension is common. The prognosis for Churg-Strauss Syndrome. Postgrad Med J. 1995;71:365-6.
RCM in infants and children is very poor and cardiac 17. Shanks M, Ignaszewski AP, Chan SY, et al. Churg-Strauss
transplantation is recommended soon after the diagnosis is syndrome with myocarditis manifesting as acute myocardial
made. infarction with cardiogenic shock: case report and review of
the literature. Can J Cardio. 2003;19:1184-8.
18. Cueto-Garcia L, Reeder G, Kyle R, et al. Echocardiographic
In this sick room, ten cents’ worth of human understanding
findings in systemic amyloidosis: spectrum of cardiac involvement
equals ten dollars’ worth of medical science.
and relation to survival. J Am Coll Cardiol. 1985;6:737-43.
—Martin H Fischer 19. Maceira AM, Joshi J, Prasad SK, et al. Cardiovascular magnetic
resonance in cardiac amyloidosis. Circulation. 2005;111:186-93.
References 20. Gertz MA, Lacy MQ, Lust JA, et al. Prospective randomized trial
of melphalan and prednisolone versus vincristine, carmustine,
1. Benotti JR, Grossman W. Restrictive cardiomyopathy. Annu. melphalan, cyclophosphamude and prednisone in the treatment
Rev. Med. 1984;35:113-25. of primary systemic amyloidosis. J Clin Oncol. 1999;17:262-7.
2. Stollberger C, Finsterer J. Extracardiac medical and neuromus- 21. Kontoghiorghes GJ. Future chelation monotherapy and
cular implications in restrictive cardiomyopathy. Clin Cardiol. combination therapy strategies in thalassemia and other
2007;30:375-80 conditions. Comparison of deferiprone, deferoxamine ICL
3. Hirotay Shimizu G, Kita Y, et al. Spectrum of restrictive 670, GT56-252, L1NAll and starch deferoxamine polymers.
Hemoglobin. 2006;30:329-47.
cardiomyopathy: report of the national survey in Japan. Am
22. Cappellini MD, Pattoneri P. Oral iron chelators. Annu Rev
Heart J. 1990;120:188-94.
Med. 2009;60:25-38.
4. Shaddy RE. Cardiomyopathies in adolescents: dilated,
23. Poppi NT, Reis MV, Aiello VD. A 20 years old man with heart
hyper trophic and restrictive. Adolesc Med. 2001;12(1): failure due to restrictive cardiomyopathy. Arq Bras Cardiol.
35-45. 2009;92:461-8.
5. Hoit BD, Gupta S. Restrictive, Obliterative and Infiltrative 24. Hayashi T, Tsuda E, Kurosaki K, et al. Electrocardiographic
Cardiomyopathies. In: Fuster V, O’ Rourke R, Walsh RA, and clinical characteristics of Idiopathic Restrictive cardio
Poole-Wilson P, (Eds). Hurst’s the heart 12th edition. McGraw myopathy in children. Circ J. 2007;71:1534-9.
Hill. Inc. 2007;851. 25. Ammash NM, Seward JB, Bailey KR, et al. Clinical profile and
6. Lee JH, Chung WB, Kang JH, Kim HW, et al. A case of outcome of idiopathic restrictive cardiomyopathy. Circulation.
chloroquine—induced cardiomyopathy that presented as sick 2000;101:2490-6.
sinus syndrome. Korean Circ J. 2010;40:604-10. 26. Guertl B, Neohammer C, Heofler G. Metabolic cardiomyopa-
7. Cetta F, O’ Leary PW, Seward JB, et al. Idiopathic restrictive thies. Int J Exp Pathol. 2000;81:349-72.
cardiomyopathy in childhood: Diagnostic features and clinical 27. Schwartz ML, Cox GF, Lin AE, et al. Clinical approach to genetic
course. Mayo Clin Proc. 1995;70:634-40. cardiomyopathy in children. Circulation. 1996;94:2021-38.
8. Zangwill S, Hamilton R. Restrictive Cardiomyopathy. Pacing 28. Case LE, Hanna R, Frush DP, et al. Fractures in children with
Clin Electrophysiol. 2009;32:S41-S43. Pompe’s disease: a potential long term complication. Pediatr
9. Sengupta PP, Krishnamoorthy VK, Abhayaratna WP, et al. Radiol. 2007;37:437-45.
Comparison of usefulness of tissue Doppler imaging versus 29. Desnick RJ, Brady R, Barranger J, et al. Clinical Guidelines
Brain natriuretic peptide for differentiation of constrictive Fabry disease, an under-recognised multisystem disorders:
pericardial disease from restrictive cardiomyopathy. Am J expert recommendations for diagnosis, management and enzyme
Cardiol. 2008;102:357-62. replacement therapy. Ann Intern Med. 2003 Feb 18;138:338-46.
10. Vijayaraghavan G, Davies J, Sadanandan DS, et al. 30. Peters FP, Vermeulen A, Kho TL. Anderson-Fabry disease:
Echocardiographic features of tropical endomyocardial disease alpha galactosidase deficiency. Lancet. 2001;357:138-40.
in South India. Br Heart J. 1983;50:450-9. 31. Parvatiyar MS, Pinto JR, Dweck D, et al. Cardiac troponin
11. Gaudalajara JF, Vera-Delgado A, Gaspar-Hernandez J, et al. mutations and restrictive cardiomyopathy. J Biomed
Echocardiographic aspects of restrictive cardiomyopathy: Biotechnol. 2010:2010:350706. Epub 2010 Jun 8.
their relationship with pathophysiology. Echocardiography. 32. Hancock EW: Cardiomyopathy differential diagnosis of
1998;15:297-314. restrictive cardiomyopathy and constrictive pericarditis. Heart
12. Chatterjee K. Primary diastolic heart failure. Am J of Geriatr 2001;86:343-9.
Cardiol. 2002;11:178-87. 33. Anderson PA. Diagnostic Problem: constrictive pericarditis or
722
13. Przybojewski JZ. Endomyocardial biopsy: a review of restrictive cardiomyopathy? Cathet Cardiovasc Diagn. 1983;9:
literature. Cathet Cardiovas Diagn. 1985;11:287-330. 01-07.
C hapter
51 Hypertrophic Cardiomyopathy
Krishnan MN
http://vip.persianss.ir
9 Non-sarcomere protein mutations like Fabry disease, ventricular volume or decrease systolic arterial pressure
PRKAG2, lysosome-associated membrane protein 2 (LAMP2) augment the gradient and vice versa. Accordingly, exercise,
cardiomyopathies mimic HCM clinically. isoproterenol or dobutamine infusion increases the gradient;
Congenital cardiomyopathies
Pathophysiology Symptoms
Symptoms of HCM include dyspnea on effort, fatigue, angina
Left Ventricular Outflow Tract Obstruction
and syncope/presyncope. Dyspnea is predominantly due to
About 70 percent of hospital-based patients with HCM have diastolic dysfunction and may be compounded by LVOTO.
LV outflow tract obstruction (gradient ≥ 30 mm Hg). In most Severity of symptoms often varies day-by-day. Symptoms are
patients the obstruction is due to systolic anterior movement more after a large meal or alcohol ingestion, which increases
(SAM) of the mitral valve and midsystolic contact with the gradient. Angina occurs due to myocardial ischemia on
septum caused by drag effect on the anterior mitral leaflet. The exertion. Syncope usually occurs during exertion although it
magnitude of the gradient is directly related to the duration of may present itself on sudden standing from supine posture.
the contact. Mitral regurgitation (MR) may occur secondary The syncope is explained by several mechanisms including
to the SAM and is usually directed posteriorly. The outflow arrhythmias and increase in outflow obstruction. CHF is rarely
gradient imposes increased wall stress and oxygen demand seen in HCM in normal sinus rhythm, but it may be seen with
and is a predictor of progression to HF. However, there is no severe obstruction to outflow, severe systolic or diastolic
consistent relation between the magnitude of gradient and risk dysfunction or advent of AF. History of palpitations may also
of sudden death. Outflow gradient is dynamic with spontaneous be there during tachyarrhythmia and may be associated with
724 variability. Interventions that increase contractility, reduce syncope.
Physical Findings Table 1
51
Differences in the physical findings of HOCM and valve aortic
Left ventricular involvement is reflected by a variably displaced stenosis
Hypertrophic Cardiomyopathy
and forceful LV impulse. Patients with non-obstructive HCM
Clinical parameter HOCM Valvar aortic stenosis
have no murmur and manifest only as forceful apical impulse
and palpable and audible fourth heart sound. Carotid pulse Jerky/bisferiens Delayed low volume,
carotid shudder
In patients with significant obstruction, the carotid pulse is
usually flicking or jerky and at times bisferiens character may JVP Prominent ‘a’ Prominent ‘a’ wave
wave, if RV may be present
be present. Apex is variably displaced and forceful. Sometimes
involvement (Bernheim effect)
a double systolic impulse may be felt over the apex. A fourth (Broady’s effect)
heart sound may also be palpable causing a ‘triple ripple’. The
Apex beat Double or triple, Heaving, S4 may be
first heart sound is usually normal. The second heart sound may forceful palpable
be normal, fused or paradoxically split with increasing severity
Thrill Rare Common
of obstruction. A fourth heart sound is usually audible over the
apex. The mid systolic murmur of LVOTO is usually 2/6 or S2 Single or reverse Single or reverse
3/6, best audible over the 3rd left intercostal space; it is seldom Ejection click No Commonly present
associated with a thrill. There may be, in addition, an apical Outflow murmur 3rd left space; no 2nd right space;
systolic murmur of mitral regurgitation. Patients with mid- carotid radiation radiates to carotids
ventricular obstruction may also have an apical systolic murmur MR Common No
although it is usually softer than with subaortic obstruction. There
HOCM = Hypertrophic obstructive cardiomyopathy; JVP = Jugular venous
may be at times a very distinctive long diastolic murmur caused pressure
by mid-ventricular narrowing and asymmetric relaxation. A
mid systolic clicking sound of mitral leaflet septal contact may DIAGNOSIS/INVESTIGATIONS
be rarely heard. The murmur of subaortic obstruction varies
significantly with maneuvers. Valsalva maneuver, standing Electrocardiography14,15
from squatting position or amyl nitrite inhalation increases the
gradient and the intensity of murmur; squatting or isometric The 12-lead electrocardiogram (ECG) is abnormal in 90
handgrip decreases the gradient and murmur. Postectopic percent of patients of HCM (Figure 1). The most common
beat causes an increase in the obstruction and murmur, while abnormalities include tall R waves, deep narrow Q waves, ST-T
being associated with a smaller pulse volume as a result of abnormalities and left atrial enlargement. Sometimes the ECG
increase in contractility due to postextrasystolic potentiation. pattern is very bizarre. The deep Q waves may at times
The differential physical findings in HCM versus valvar aortic mimic myocardial infarction. About 25 percent of cases have
stenosis are depicted in Table 1. left anterior hemiblock. Deep negative T in lateral leads is
725
Figure 1: 12 lead electrocardigram in a 7-year-old with hypertrophic cardiomyopathy with both left and right ventricular outflow tract
obstruction showing both left and right ventricular hypertrophy.
http://vip.persianss.ir
9 characteristic of apical form of HCM. Normal ECG is seen
Box 2: Conditions causing left ventricular hypertrophy
in five percent of cases and predict a favorable cardiovascular or thickened interventricular septum
course, but is not predictive of SCD. The ECG does not
Congenital cardiomyopathies
A B
C
726 Figures 2A to C: Echocardiogram in parasternal long-axis view: A. Shows hypertrophy of left ventricular septum disproportionate to free wall
hypertrophy; B. Septal thickness to posterior wall thickness ratio of 1.5 is characteristic; C. Measurement of thickness of interventricular septum
and posterior wall in short-axis view. Ao = Aorta; LA = Left atrium; LV = Left ventricle; PW = Posterior wall; RV = Right ventricle; VS = Ventricular
septum.
Table 2
51
Indices for echocardiographic assessment of left ventricular hypertrophy by echocardiography
Hypertrophic Cardiomyopathy
Index Description Score
Wigle Thickness of basal septum in mm 15–19 : 1
20–24 : 2
25–29 : 3
≥ 30 : 4
Spirito’s score Left ventricular hypertrophy extent 1 segment—mild
2 segments—moderate
3 or more—severe
Spirito-Maron index Left ventricular hypertrophy Sum of maximum thickness of all 4
extent and severity segments between mitral leaflet tip and
papillary muscle in short-axis view
Maximal wall thickness Maximum thickness of any wall segment ≥ 30 mm
The degree of LVH varies throughout life. Although the Systolic anterior motion of the mitral valve may also
gross phenotypic expression and clinical profile of HCM occur in conditions other than HCM (pseudo SAM). Mitral
may occasionally be identified in infants and young children, annulus is an integral part of LV; motion exhibited by mitral
marked LVH is rarely documented during the 1st year of valve may be related to motion of mitral annulus and/or left
life. Rapid changes in LV morphology often occur during ventricular wall. Any condition in which posterior LV wall
adolescence, when LV wall thickness may increase rapidly. motion is exaggerated can lead to SAM. In true SAM the peak
Genetic studies among large families demonstrated that leaflet anterior motion is complete before the peak posterior
morphological LVH reaches a plateau at the third decade of wall movement; in pseudo SAM the peak of AML movement
life in myosin heavy-chain and in tropomyosin mutations, occurs after the peak of PW movement. SAM may be produced
whereas it increases continuously though life in cardiac by various parts of the mitral valve apparatus like anterior
myosin-binding protein C mutations. mitral leaflet alone, anterior and posterior leaflets or chordae
alone. SAM is thought to be produced by venturi effect of
Left Ventricular Outflow Obstruction blood flowing across the hypertrophied septum or malposition
of papillary muscles. The aortic valve motion may show a mid
A common accompaniment to hypertrophy in HCM is systolic closure of the anterior leaflet indicating alteration in
dynamic obstruction of the LVOT. Up to one-third of patients aortic blood flow (Figure 3B).
with HCM will have obstruction under basal (resting) Spectral Doppler echocardiography helps in determining
conditions (defined as gradients ≥ 30 mm Hg). Another one- the presence and severity of LVOTO. The classic continuous
third or more of patients will have labile, physiologically wave Doppler recording shows relatively slow increase in
provoked gradients (< 30 mm Hg at rest and ≥ 30 mm Hg velocity in early systole and peaks in late systole producing
with physiologic provocation). The final one- third of patients a dagger-shaped velocity envelope (Figure 4). Color Doppler
will have the non-obstructive form of HCM (gradients < 30 helps to identify the location of the obstruction and also the
mm Hg at rest and with provocation). The echocardiographic presence and severity of MR (Figure 5). The jet of MR is
hallmark of obstruction is SAM of the mitral valve (Figure directed laterally and posteriorly and predominates during mid
3A). The anterior mitral leaflet moves anteriorly toward and late systole. An anteriorly directed jet should suggest an
the interventricular septum (IVS) shortly after the onset intrinsic abnormality of the mitral valve. The mitral diastolic
of systole and returns to its normal position just before the filling pattern is usually indicative of impaired relaxation with
onset of diastole. The finding is best seen with M-mode E/A reversal or restrictive filling pattern. In mid ventricular
echocardiography. There is close correlation between the obstruction blood may actually flow from apex to the body
severity of obstruction and the duration of mitral leaflet— of the ventricle during diastole producing a high velocity
septal contact. The gradient is given by the equation: diastolic flow.
LVOT gradient = (Septal contact time/Time from onset of
SAM to septal contact) × 25 + 25 mm Hg. Hemodynamic Evaluation and Ventriculography17
Systolic anterior motion of mitral valve and obstruction are
classically dynamic and may not be always present at rest, but Pull-back tracings from left ventricle will show gradient at
may appear on provocation such as Valsalva maneuver, amyl the LVOT in those with resting obstruction. The aortic tracing
nitrite inhalation or intravenous isoproterenol. may show ‘spike and dome’ pattern in those with significant 727
http://vip.persianss.ir
9
Congenital cardiomyopathies
A B
Figures 3A and B: M mode in echocardiogram showing: A. SAM (arrow); B. Aortic valve presystolic closure (arrow)
Figure 4: Doppler in left ventricular outflow tract showing dagger Figure 5: Color Doppler showing left ventricular outflow tract (LVOT)
shaped velocity profile turbulence (arrow) and mitral regurgitation (MR). Ao = Aorta; LA = Left
atrium; LV = Left ventricle.
gradients; this represents the rapid early systolic ejection show hypertrophied ventricle with near obliteration of cavity
followed by slowing of the ejection beyond midsystole in systole, SAM and MR.
in the wake of progressive obstruction in the mid systole
characteristic of HOCM (Figure 6). Postextrasystolic aortic Cardiac Magnetic Resonance Imaging19-21
tracing shows decrease systolic pressure and pulse pressure
in the beat after the pause with an increase in the LV pressure In the last few years, cardiovascular magnetic resonance
and the gradient. During the long diastole, although increase (CMR) has emerged not only as a diagnostic tool, but also as
in the LV volumes tend to reduce the obstruction, the a study with prognostic valve, by characterizing myocardial
postextrasystolic increase in contractility (postextrasystolic fibrosis with great accuracy in HCM patients. Additionally,
potentiation) over-rides this effect and causes greater obstruc CMR identifies the type of hypertrophy, analyses the
tion (Brockenbrough-Braunwald-Morrow sign) (Figure 7).18 ventricular function, estimates the intraventricular gradient
The LV and right ventricular end diastolic pressures are and allows the determination of differential diagnosis.
usually elevated, so also the left atrial (LA) mean pressure. Mild Magnetic resonance is more sensitive and accurate to assess
elevation of PA pressure may be present. Tall V waves in the hypertrophy and LV mass than echocardiography. European
728 pulmonary artery wedge pressure tracing represent significant and American Societies of Cardiology recently accepted
MR or elevated LA pressures. Left ventriculography will CMR as the primary modality of imaging in suspected HCM.
respect any specific coronary territory and in the majority 51
of HCM subjects is found mostly at the junction between
the interventricular septum and right ventricular free wall
Hypertrophic Cardiomyopathy
conforming to necropsy studies. Two patterns of LGE have
been described: a localized, homogeneous confluent pattern
denoting better prognosis and a more diffuse, patchy and
heterogeneous pattern, usually associated with more than 2
factors for SCD and a worse prognosis.
Differentiating HCM from athlete’s heart is important as
competitive sports in patients with HCM carries high risk of
SCD.22 HCM is the single most common disease causally
linked to athletic field deaths, accounting for about one-third
of cases.
In HCM the septal thickness in usually >15 mm; the range
between 13 to 15 mm represents a gray zone. Ventricular
Figure 6: Left ventricle (LV) and aortic tracing showing gradient and septal thickness of 13 to 15 mm can be seen in about 2 percent
spike and dome aortic tracing of highly trained male athletes. The major differentiating
points between HCM and athlete’s heart is given in Table 3.
A 24 hours Holter recording is recommended in HCM as
an initial evaluation or when the patient develops palpitation
or giddiness.23,24
Presence of non-sustained ventricular arrhythmias is a risk
factor for SCD and identifies patients who may be candidates
for implantable cardiac defibrillator (ICD). The test may be
repeated every year. Invasive electrophysiologic testing has
little value in assessing the risk of SCD.
Treadmill ECG may be useful for assessing risk as
abnormal blood pressure response like failure for SBP to rise
> 20 mm or drop in SBP by > 20 mm portends high risk of
SCD.25,26
Exercise test may be done in patients with HCM—
1. To assess the functional capacity,
2. To assess the risk of SCD and
Table 3
Differential features between HCM and Athlete’s heart
http://vip.persianss.ir
9 3. To provoke gradients in those who have resting gradient each of the HCM risk factors has a low positive predictive
<30 mm Hg. values (approx 10–20%) and modest negative predictive
Invasive coronary angiography is indicated in patients value (approx 85–95%). Multiple risk markers in individual
Congenital cardiomyopathies
who complain of angina-like chest pain with intermediate patients may not indicate higher risk; the vast majority of
likelihood for coronary artery disease (CAD), prior to surgical patients with more than one risk marker will not experience
septal myectomy (SSM) or percutaneous transluminal septal SCD.29 The number of risk factors did not correlate with the
myocardial ablation (PTSMA). Assessment of coronary rate of subsequent appropriate ICD discharges. Data suggest
anatomy with computed tomographic angiography is that the presence of a single risk marker may be sufficient
reasonable for patients with HCM with chest discomfort and to warrant ICD placement in most patients; however these
a low likelihood of CAD to assess for possible concomitant decisions have to be individualized with regard to age,
CAD. Assessment of ischemia or perfusion abnormalities strength of the risk factor and the risk benefit of lifelong ICD
suggestive of CAD with single photon emission computed therapy.
tomography or positron emission tomography myocardial The usefulness of the following potential SCD risk
perfusion imaging (because of excellent negative predictive modifiers is unclear but might be considered in selected
value), is reasonable in patients with HCM with chest patients with HCM for whom risk remains borderline after
discomfort and a low likelihood of CAD to rule out documentation of conventional risk factors:
concomitant CAD. a. CMR imaging with LGE.
b. Double and compound mutations (i.e. > 1).
Risk Stratification27,28 c. Marked LVOT obstruction. Invasive electrophysiologic
testing as routine SCD risk stratification for patients with
Assessment of risk of SCD is an integral part of the patients HCM should not be performed.
with HCM. Table 4 outlines the major risk factors for SCD in
HCM. Treatment
Several studies investigated the risk of SCD with
combination of major risk factors. The combination of history Treatment strategies in HCM are tailored along:
of syncope with family history is a significant risk factor for 1. Control of symptoms.
SCD. Patients with 2 or more risk factors have an estimated 2. Prevention of sudden cardiac death.
annual SCD risk of 4 to 5 percent. 3. Prevention and management of atrial fibrillation.
A minority of HCM patients have increased risk for SCD 4. Management of dilated phase of HCM.
with a rate of above 1 percent per year. Other than cardiac arrest, A large proportion of patients presenting with HCM are
asymptomatic and can achieve a normal life expectancy. It
is essential to educate these patients and their families about
Table 4
the disease process and to screen the first degree relatives.
Risk factors for sudden cardiac death in hypertrophic
cardiomyopathy They should be advised to avoid strenuous physical activity
or competitive athletics. Risk stratification of SCD should be
Parameter Definition performed in all patients irrespective of symptoms. Hydration
1. A
borted sudden cardiac Documented cardiac arrest and avoidance of situations where vasodilatation may occur
arrest or VF are important in patients with resting or provocable LV-
2. Spontaneous sustained VT VT lasting for > 30 s or OT obstruction. High dose diuretics and vasodilators and
requiring cardioversion inotropes should be avoided.
3. Family history of premature SCD is first degree relatives Beta-blockers are the mainstay of pharmacologic therapy
SCD less than 40 years and the first line agents because of their negative inotropic
4. Unexplained syncope Syncope without a known effects and ability to attenuate adrenergic induced tachycardia.
causal factor, ≥2 episodes in They act by reducing LVOT obstruction and myocardial
the previous year ischemia and improving diastolic filling of LV.
5. Nonsustained VT on Holter > 3 consecutive ventricular In patients, who cannot tolerate beta blockers or
complexes at a rate of > 120 unresponsive to beta blockers, non-dihydropyridines calcium
beats per minute channel blockers (CCB) may provide symptomatic relief by
6. Extreme LV wall thickness Maximum LV wall thickness their negative inotropic and rate lowering effects. Verapamil
more than or equal to 30 mm or diltiazem should be cautiously given in patients with
7. A
bnormal exercise BP Failure to increase by at least severe obstruction, elevated LA pressure and low systemic
response 20 mm or a drop of ≥ 20 mm blood pressure because a drop in the blood pressure may
during effort trigger severe outflow obstruction and precipitate pulmonary
730 BP = Blood pressure; LV = Left ventricle; SCD = Sudden cardiac death; VF edema. Dihydropyridine class of CCB should not be used in
= Ventricular fibrillation; VT = Ventricular tachycardia. obstructive HCM.
Those who remain symptomatic despite use of beta repair, in addition to myectomy, may be most appropriate for 51
blockers and CCB alone or in combination may benefit from selected patients with severe MR caused by primary valvular
disopyramide due to its negative inotropic effect. The use of disease. Septal myectomy is established as a proven approach
Hypertrophic Cardiomyopathy
disopyramide alone without beta blockers or verapamil is for reversing the consequences of HF by providing permanent
potentially harmful in the treatment of HCM with AF because amelioration of obstruction (and relief of MR) and restoring
it may enhance atrioventricular conduction and increase the functional capacity and an acceptable quality of life at any
ventricular rate. Oral diuretics in patients with non-obstructive age. The procedure results in excellent long-term survival of
HCM may be administered when dyspnea persists despite the 90 percent at 10 years, superior to non-operated patients, and
use of beta blockers and/or verapamil. reduces the incidence of SCD.
The use of angiotensin converting enzyme inhibitors or
receptor blockers in HCM with preserved systolic function is Percutaneous Transluminal Septal
not well established and these drugs should be used cautiously Myocardial Ablation31
in patients with LVOT obstruction.
Alcohol septal ablation is a catheter-based procedure in
Septal Reduction Therapy which 96 percent alcohol is injected through a major septal
artery supplying the basal hypertrophied septum (Figures 8A
Septal reduction therapy (SRT) involves invasive methods of and B). The eligibility is same as SSM; however, at present
reducing the septal thickness viz. SSM and PTSMA. Septal the procedure is reserved for those who are poor surgical
reduction therapy is indicated in eligible (those with septal candidates or those who refuse surgery. Ideal PTSMA
hypertrophy and SAM) patients with LVOTO (gradient basal candidate is subaortic SAM-related LVOT obstruction ±
> 30 mm Hg and/or provocable > 50 mm Hg) with drug- SAM-related MR with basal septum thickness > 18 mm,
refractory symptoms. but < 30 mm; while those with marked elongation of AML,
severe MR due to MV abnormalities, markedly thick and
Surgical Septal Myectomy30 fibrotic septum, abnormal insertion of papillary muscles are
poor candidates for the procedure. After measurement of basal
The first choice of septal reduction therapy in HCM is SSM. gradient, the septal branch is wired; the distribution area of
Surgical septal myectomy, when performed in experienced the septal branch is ascertained using myocardial contrast
centers, can be beneficial for the majority of eligible patients echocardiography using Levovist through an over the wire
with HCM with severe drug-refractory symptoms and LVOT balloon in the septal branch; the balloon is inflated and a small
obstruction. In the hands of experienced operators the success quantity of contrast is injected to rule out back-leak; 1 to 2 mL
rate is around 95 percent, surgical mortality < 1 percent and of alcohol is then slowly injected keeping the balloon inflation.
major complications 2 to 3 percent. A rectangular trough Echocardiographic control is extremely important as the septal
of septum from below the aortic valve to the distal septum branches have highly variable area of supply; misplacement
beyond the septal contact (or up to the insertion of papillary of alcohol into wrong branch could not only be ineffective,
muscle in extended myectomy) is removed. Mitral valve but could cause remote infarction with serious complications.
A B
731
Figures 8A and B: Coronary angiogram before (A) and after (B) Percutaneous transluminal septal myocardial ablation (PTSMA)
http://vip.persianss.ir
9 The area of myocardium undergoes chemical necrosis and prevention ICDs was 3 to 4 times more frequent than in other
later scarring. A final angiography control excludes left patients in that registry (10.3% per year compared with 2.6%
coronary artery damage and verifies septal branch occlusion per year).33 Alternatively, incidence of sustained ventricular
Congenital cardiomyopathies
while hemodynamic measurements confirm the immediate arrhythmias after surgical myectomy is extremely low (0.2–
result of septal ablation. Contraindications include the failure 0.9% per year).
of myocardial contrast echocardiography to identify a target
septal branch, the echocardiographic contrast opacification of Dual Chamber Pacing34
any cardiac structure other than the target septal area, or insecure
balloon positioning that bears the risk of alcohol reflux during A small number of patients with HOCM may draw symptomatic
injection. Furthermore, alcohol injection should be avoided benefit from dual chamber pacing. Pacing the right ventricular
if there is any suspicion of collateral flow that could lead to apex with maintenance of atrioventricular synchrony results
infarction far from the target septal area. About 90 percent of in a decrease in the LVOT gradient and improvement of
patients will have significant reduction in the gradient, which symptoms in a subset of patients. The exact mechanism of
will continue to decrease over time. Symptomatic improvement improvement with pacing remains unknown; the decrease in
parallels the hemodynamic changes. gradient may be caused by alteration in the timing of septal
Complications of PTSMA include bundle branch block, contraction. Although there was an initial enthusiasm for
complete heart block (CHB) and reflux of alcohol into left dual-chamber pacing as a primary treatment for patients with
anterior descending artery. Right bundle branch block obstructive HCM, subsequent data demonstrated long-lasting
occurs in about 50 percent of patients after septal ablation. beneficial results in only a small minority of patients, whereas
In approximately half of patients undergoing alcohol septal most perceived improvement was judged to be placebo effect.
ablation, temporary complete atrioventricular block occurs
during the procedure. The incidence of persistent CHB used to Prevention of Sudden Cardiac Death35,36
be > 10 percent in the earlier series of PTSMA; however with
myocardial contrast echocardiographic control and limited The only treatment modality, which has been proven to
use of alcohol (< 2 mL), the incidence has come down to < reduce SCD in HCM is implantation of ICD. The decision
5 percent almost equaling that of SSM. The block usually to place an ICD should include application of strength of
occurs within 48 hours of the procedure although it may be as evidence, benefits, risks and individual clinical judgment. The
late as 10 days; patients with pre-existing left bundle branch indications for ICD implantation is outlined in Table 5.
block are more prone to CHB. Approximately 5 percent of The usefulness of ICD is uncertain in HCM with isolated
patients have sustained ventricular tachyarrhythmia during non-sustained ventricular tachycardia (NSVT) or abnormal
hospitalization. In-hospital mortality is now < 1.5 percent. blood pressure response with exercise. The complications
A most feared complication is iatrogenic reflux of alcohol of ICD in HCM include inappropriate discharge (25%), lead
into the left anterior descending artery, causing vessel complications (6–13%), device infection (4–5%) and bleeding
occlusion and anterior wall myocardial infarction. This can be and thrombotic complications (2–3%). Dual chamber ICDs are
avoided, however, by the routine use of a slightly oversized reasonable for patients with elevated resting outflow gradient
balloon compared to the septal artery diameter, and by (> 50 mm Hg) and significant heart failure symptoms.
keeping the balloon inflated for at least 10 minutes after the
last alcohol injection. Management of Atrial Fibrillation37
Long-term results of PTSMA are encouraging with
sustained abolition of gradient and persistent symptomatic Atrial fibrillation in patients with HCM usually causes
improvement. Recently published data from a larger cohort hemodynamic deterioration due to fast ventricular rate and
of 347 patients has shown 94 percent survival after 5 years withdrawal of atrial booster action. Ventricular rate control can be
and 87 percent after 10 years, which is comparable to the achieved with high doses of beta blockers or non-dihydropyridine
results of large myectomy studies. Many studies have raised CCB. Disopyramide and amiodarone can be given to prevent the
the concern over the occurrence of ventricular tachyarrhythmia recurrences in paroxysmal AF. Radio frequency ablation may
and SCD among patients who have undergone PTSMA. The be considered in those who have refractory symptoms or who
presence of a scar in the septum may act as a substrate for are unable to take antiarrythmic drugs. Maze procedure with
arrhythmias. In a selected subset of 42 patients with an ICD closure of LA appendage is reasonable either during SSM or as
or permanent pacemaker that enabled detection of device- an isolated procedure in selected patients.
stored electrograms, the annualized event rate (ventricular
tachycardia, ventricular fibrillation, and/or appropriate ICD Physical Activity38
discharge) was 4.9 percent per year.32 Similarly, the multicenter
HCM ICD registry of 506 patients demonstrated that the rate of It may be reasonable for patients with HCM to indulge in
732 appropriate ICD therapy among ablation patients with primary low-intensity sports or recreational activities. They should
Table 5
51
Indications for implantable cardiac defibrillator in hypertrophic cardiomyopathy
Hypertrophic Cardiomyopathy
Definite:
1. P
rior documented cardiac arrest, ventricular fibrillation or
hemodynamically significant ventricular tachycardia
Probable:
1. S
udden death presumably caused by hypertrophic cardiomyopathy
in one or more first degree relatives
2. A maximum left ventricle wall thickness more than or equal to 30 mm
3. Unexplained syncope One or more recent episodes
4. Selected patients with non-sustained ventricular tachycardia Particularly those less than 30 years of age and in the
presence of other risk factors
5. Abnormal blood pressure response with exercise In the presence of other sudden cardiac death risk factors
http://vip.persianss.ir
9 symptoms and to identify those patients who may be at risk for 13. Wigle ED, Rakowski H, Kimball BP, et al. Hypertrophic
SCD. In the future, genetic testing and identification of genes cardiomyopathy. Clinical spectrum and treatment. Circulation.
will continue to help clarify the treatment and management of 1995;92:1680-92.
Congenital cardiomyopathies
patients with HCM. 14. Montgomery JV, Harris KM, Casey SA, et al. Relation of
electrocardiographic patterns to phenotypic expression and
clinical outcome in hypertrophic cardiomyopathy. Am J
Temperance and labor are the two real physicians of man.
Cardiol. 2005;96:270.
—Jean Jacques Rousseau 15. McLeod CJ, Ackerman MJ, Nishimura RA, et al. Outcome
of patients with hypertrophic cardiomyopathy and a normal
Acknowledgment electrocardiogram. J Am Coll Cardiol. 2009;54:229.
16. Losi M, Nistri S, Galderisi M, et al. Echocardiography in
I wish to thank Professor Dr B Ramesh and Dr AC Nagamani, patients with hypertrophic cardiomyopathy: usefulness of old
Associate Professor of Cardiology at Sri Jayadeva Institute and new techniques in the diagnosis and pathophysiological
of Cardiovascular Institute of Sciences and Research for their assessment. Cardiovascular Ultrasound. 2010;8:7-26.
17. Grossman W. Profiles in dilated (congestive) and hypertrophic
contribution of the images in this chapter.
cardiomyopathies. In: Grossman W, (Ed). Cardiac cath
eterization and angiography. Philadelphia: Lea and Febiger;
References 1986. pp. 420-21.
18. Brockenbrough EC, Braunwald E, Morrow AG. A hemo
1. Gersh BJ, Maron BJ, Bonow RO, et al. 2011ACCF/AHA dynamic technic for the detection of hypertrophic subaortic
Guideline for the Diagnosis and Treatment of Hypertrophic stenosis. Circulation. 1961;23:189-94.
Cardiomyopathy.A Report of the American College of 19. Shiozaki AA, Kim RJ, Parga JR, et al. Cardiovascular magnetic
Cardiology Foundation/American Heart Association Task Force resonance in hypertrophic cardiomyopathy. Arq Bras Cardiol.
on Practice Guidelines. Circulation. 2011;124:e783-e831. 2007;88(2):243-48.
2. Alcalai R, Seidman JG, Seidman CE. Genetic basis of 20. Moon JC, Fisher NG, McKenna WJ, et al. Detection of apical
hypertrophic cardiomyopathy: From bench to the clinics. J hypertrophic cardiomyopathy by cardiovascular magnetic
Cardiovasc Electrophysiol. 2008;19:104. resonance in patients with non-diagnostic echocardiography,
3. Maron BJ, Towbin JA, Thiene G, et al. Contemporary Heart. 2004;90:645-49.
definitions and classification of the cardiomyopathies. An 21. Rickers C, Wilke NM, Jerosch-Herold M, et al. Utility of
American Heart Association Scientifi Statement. Circulation. cardiac magnetic resonance imaging in the diagnosis of
2006;113:1807. hypertrophic cardiomyopathy. Circulation. 2005;112:855-61.
4. Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, 22. Cheng TO. Hypertrophic cardiomyopathy vs athlete’s heart.
and therapeutic implications of gene testing for hypertrophic International Journal of Cardiology. 2009;131:151-5.
cardiomyopathy. J Am Coll Cardiol. 2009;54:201. 23. Maron BJ, Savage DD, Wolfson JK, et al. Prognostic
5. Maron BJ, Seidman CE, Ackerman MJ, et al. What’s in a significance of 24 hours ambulatory electrocardiographic
name? Dilemmas in nomenclature characterizing hypertrophic monitoring in patients with hypertrophic cardiomyopathy: a
cardiomyopathy and left ventricular hypertrophy. Circ prospective study. Am J Cardiol. 1981;48:252-7.
Cardiovasc Genet. 2009;2:8. 24. Monserrat L, Elliott PM, Gimeno JR, et al. Non-sustained
6. Ross J Jr, Shabetai R, Curtis G, et al. Nonobstructive and ventricular tachycardia in hypertrophic cardiomyopathy: an
obstructive hypertrophic cardiomyopathies West J Med. independent marker of sudden death risk in young patients, J
1979;130:325-49. Am Coll Cardiol. 2003;42:873-9.
7. Teare D. Asymmetrical hypertrophy of the heart in young 25. Sadoul N, Prasad K, Elliott PM, et al. Prospective prognostic
adults. Br Heart J. 1958;20:1-8. assessment of blood pressure response during exercise in
8. Maron BJ, Gardin JM, Flack JM, et al. Assessment of the patients with hypertrophic cardiomyopathy, Circulation.
prevalence of hypertrophic cardiomyopathy in a general 1997;96:2987-91.
population of young adults: Echocardiographic analysis of 26. Olivotto I, Maron BJ, Montereggi A, et al. Prognostic value
4111 subjects in the Cardia Study. Circulation. 1995;92:785. of systemic blood pressure response during exercise in a
9. Maron BJ. Hypertrophic cardiomyopathy: A systematic review. community-based patient population with hypertrophic
JAMA. 2002;287:1308. cardiomyopathy. J Am Coll Cardiol. 1999;33:2044-51.
10. Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, 27. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in
and therapeutic implications of genetic testing for hypertrophic hypertrophic cardiomyopathy: identification of high risk
cardiomyopathy. J Am Coll Cardiol. 2009;54:201-11. patients. J Am Coll Cardiol. 2000;36:2212-8.
11. Tanigawa G, Jarcho JA, Kass S, et al. A molecular basis for 28. Maron BJ. Contemporary insights and strategies for risk
familial hypertrophic cardiomyopathy: an alpha/beta cardiac stratification and prevention of sudden death in hypertrophic
myosin heavy chain hybrid gene. Cell. 1990;62:991-8. cardiomyopathy. Circulation. 2010;121:445-56.
12. Maron BJ, Bonow RO, Cannon RO, et al. Hypertrophic 29. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter
cardiomyopathy: interrelations of clinical manifestations, patho defibrillator and prevention of sudden cardiac death in
physiology, and therapy. N Engl J Med. 1987;316:780-9, 884- hypertrophic cardiomyopathy. JAMA. 2007;298;405-12.
52.
734
30. Ommen SR, Olivotto I, Betocchi S, et al. The effect of
surgical myectomy on survival of patients with hypertrophic
38. Pelliccia A, Fagard R, Bjornstad HH, et al. Recommendations
for competitive sports participation in athletes with cardio
51
cardiomyopathy. J Am Coll Cardiol. 2004;43(Suppl)A:215 A. vascular disease: a consensus document from the Study
Hypertrophic Cardiomyopathy
31. Rigopoulos AG, Panou F, Kremastinos DT, et al. Alcohol Group of Sports Cardiology of the Working Group of
Septal Ablation in Hypertrophic Obstructive Cardiomyopathy. Cardiac Rehabilitation and Exercise Physiology and the
Hellenic J Cardiol. 2009;50:511-22. Working Group of Myocardial and Pericardial Diseases of
32. Noseworthy PA, Rosenberg MA, Fifer MA, et al. Ventricular the European Society of Cardiology. Eur Heart J. 2005;26:
arrhythmia following alcohol septal ablation for obstructive 1422-45.
hypertrophic cardiomyopathy. Am J Cardiol. 2009;104:128-32. 39. Autore C, Conte MR, Piccininno M, et al. Risk associated with
33. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter pregnancy in hypertrophic cardiomyopathy. J Am Coll Cardiol.
defibrillators and prevention of sudden cardiac death in 2002;40:1864-69.
hypertrophic cardiomyopathy. JAMA. 2007;298:405-12. 40. Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical
34. Vatasescu R, Evertz R, Mont L, et al. Biventricular/Left Ven- profile, and significance of left ventricular remodeling in the
tricular Pacing in Hypertrophic Obstructive Cardiomyopathy: end-stage phase of hypertrophic cardiomyopathy. Circulation.
An Overview Indian Pacing and Electrophysiology Journal. 2006;114:216-25.
2012;12(3):114-23. 41. Towbin JA. Cardiomyopathy and heart transplantation in
35. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter- children. Curr Opin Cardiol. 2002;17:274-79.
defibrillators and prevention of sudden cardiac death in 42. Marian AJ. Experimental Therapies in Hypertrophic Cardio-
hypertrophic cardiomyopathy. JAMA. 2007;298:405-12. myopathy. J Cardiovasc Transl Res. 2009;2(4):483-92.
36. Maron BJ, Spirito P. Implantable defibrillators and prevention
of sudden death in hypertrophic cardiomyopathy. J Cardiovasc Other Suggested Reading
Electrophysiol. 2008;19:1118-26. 1. Braunwald’s Heart Disease: A Textbook of Cardiovascular
37. Olivotto I, Cecchi F, Casey SA, et al. Impact of atrial fibrillation Medicine. 9th Ed. pp. 1582-94.
on the clinical course of hypertrophic cardiomyopathy. 2. Hurst. The Heart. 13th Ed. pp. 837-64.
Circulation. 2001;104:2517-24.
735
http://vip.persianss.ir
C hapter
52 Endocardial Fibroelastosis
Endocardial Fibroelastosis
hypertrophy leading to myocardial oxygen demand and Impaired contraction and relaxation together with MR leads to
supply mismatch, resulting in subendocardial injury, which is increased left ventricular end-diastolic pressure (LVEDP) that
thought to be the trigger to produce EFE. EFE is also seen leads to increased mean LA pressure and pulmonary venous
after myocardial infarction.17 hypertension (PVH), PVH is responsible for symptoms of
dyspnea and leads to development of pulmonary arterial
Pathophysiology hypertension (PAH), which ultimately gives rise to right
heart failure. In fetal life, it may lead to development of non-
Normal endocardium is thin and transparent. In EFE, endo immune hydrops fetalis.12 In contracted type, PAH develops
cardium is diffusely thicked upto 1 to 2 mm due to proliferation early and is more severe. Abnormal endocardium with
of collagen and elastic tissue and deposition of extracellular global hypokinesia sets the stage for mural thrombosis with
matrix. The characteristic appearance of endocardium in consequent systemic embolization.19
EFE is described as pearly white or milky white, glistening
and opaque. In the dilated type of pimary EFE, both LV Clinical Features
and left atrium (LA) are dilated. LV assumes a spherical
shape. Endocardial thickening also affects mitral valve
Symptoms
and other cardiac chambers.18 LV dilatation along with
abnormal origin of papillary muscles; poor LV function leads Infants present with dyspnea, wheezes, tacyhpnea, feeding
to mitral regurgitation (MR) of various grades. High origin of difficulties and failure to thrive. In some neonates, presentation
papillary muscles together with short and thick chordae results is acute (acute LVF) and the condition of the infant rapidly
in improper coaptation of mitral leaflets in systole. Aortic deteriorates. It is the fulminant presentation of EFE.20 It is
valve is also involved in 50 percent of cases. Myocardial one of the causes of sudden death in infancy.21 In other cases,
thickness remains normal. Aorta and coronary arteries are not presentation is more insidious. Sometimes the infant presents with
involved.8 diaphoresis, abdominal pain or with recurrent chest infection.
In contracted type, the LV endocardium resembles the
dilated type, but the LV remains normal or hypoplastic Signs
(Figure 1). Similar morphologic changes in endocardium occur
in secondary type of EFE, but they are more often patchy.9 Infants with EFE are tachypneic. There is no cyanosis, but
peripheral cyanosis may be seen in severe cases of heart
failure. Tachycardia is usually present with a normal to low
volume pulse. Jugular venous pressure is raised when there is
right heart failure. Apex is displaced down and out. Thrill is
uncommon in spite of significant MR due to LV hypokinesia.
In contracted type, apex is right ventricular type type due
to PAH. Hepatomegaly is commonly seen. On auscultation
S1 is diminished, S2 is closely split with loud P2. A loud S3
is commonly heard widely throughout the precordium.18
Although MR is common, presence of murmur is uncommon
as LV is unable to generate sufficient force. Absence of murmur
in presence of cardiomegaly and congestive heart failure
(CHF) is one of the important diagnostic feature of EFE.22
Investigation
Electrocardiography
Sinus tachycardia is usually seen. Rarely supraventricular and
ventricular tachycardia, atrial fibrillation and atrioventricular
blocks may be detected. EFE has been implicated in
congenital complete heart block.23 QRS axis is usually normal
Figure 1: Opened out left ventricular inflow tract shows small size of unless PAH is seen producing a right axis. P wave indicate
the left ventricle (LV) with smoothened out trabeculae and pearly white
LA enlargement or biatrial enlargement. In dilated type, 737
endocardium. The mitral valve (MV) is dysplastic. Note the presence of
patent foramen ovale (PFO) (arrow). Courtesy: Dr. Pradeep Vaideeshwar left ventricular hypertrophy is usually present with narrow
http://vip.persianss.ir
9 ‘q’ in V5 and V6 due to volume overload secondary to MR.
Flattening and inversion of T waves in lateral leads are also
seen in majority of cases. In contracted type, features of right
Congenital cardiomyopathies
Chest X-ray
Cardiomegaly is conspicuous in chest X-ray of EFE. In dilated
type, it is due to LV and LA enlargement and in contracted
type, it is due to right atrial and right ventricular enlargement
secondary to PAH. In both types, features of PVH are seen.23 Figure 2: Echocardiography in endocardial fibroelastosis (done in
EFE is one of the causes of massive cardiomegaly in newborns 1987 in a 4 months baby) showing bright echogenic endocardium of
and infants. Although there is marked cardiomegaly in dilated left ventricle, mitral valve, papillary muscles seen in parasternal long-
type, the aorta and pulmonary trunk remains normal, which axis view. Right ventricle is dilated. The mother had mumps in the first
trimester
helps in differentiating EFE from other congenital heart
diseases.
finding is bright echogenic thickened endocardium seen on
Echocardiography 2D echocardiography and M-mode (Figures 2 and 3A).24
LV shows global hypokinesia and MR is detected by
In echocardiography, LV and LA are dilated, LV dilatation is color Doppler (Figure 3B) and its severity can be graded.
accompanied by increased wall thickness. The characteristic In presence of severe MR, the LA may be hugely dilated.
A B
Figures 3A and B: A. M- mode at the papillary muscle level shows dilated and hypertrophied left ventricle with hyperechogenicity of the
papillary muscle and posterior wall; B. Transthoracic echocardiogram in apical four chamber view shows deformed dysplastic mitral valve with
738 hyperechogenicity of papillary muscle (arrow), posterior wall and color Doppler shows severe mitral regurgitation. LA = Left atrium; LV = Left
ventricle; MR = mitral regurgitation; RA = Right atrium; RV = Right ventricle. Courtesy: Dr. IB Vijayalakshmi
Echocardiography also helps in assessing pulmonary Infiltrating and Storage Disease 52
arterial pressure. In contracted type, LV cavity is small
with hypertrophied myocardium and bright echogenic Infiltrative and storage disease like Pompe disease, glycogen
Endocardial Fibroelastosis
endocardium. PAH is particularly common in contracted storage disease and mucopolysaccharidosis may present with
type as determined from tricuspid regurgitation jet, which is similar findings, but marked generalized thickening of the
usually present. Intrauterine detection is also possible by fetal cardiac structures including right ventricular free wall along
echocardiography.25 Doppler echocardiography study is the with other systemic findings help to differentiate it from
tool of choice for diagnosis and follow-up. EFE.32
http://vip.persianss.ir
9 mechanical support and heart transplantation. The overall for the role of mumps virus as an etiologic agent. Circulation.
1997;95:133-9.
prognosis is gloomy; survival beyond two years of age is
rare. 12. Rodriguez MM, Bruce JH, Jimenez XF, et al. Nonimmune
Congenital cardiomyopathies
740
Disease, 1st edition. Jaypee Brothers Medical Publishers. for management of heart failure in children. J Heart Lung 52
2008,pp.71-3. Transplant. 2004;23:1313-33.
29. Ahmed MI, McGiffin DC, O’Rourke RA, et al. Mitral 34. Blume ED, Canter CE, Spicer R, Gauvreau K, Colan S,
Endocardial Fibroelastosis
regurgitation. Curr Probl Cardiol. 2009;34:93-136. Jenkins KJ. Prospective single-arm protocol of carvedilol
30. Bohn D, Benson L. Diagnosis and management of pediatric in children with ventricular dysfunction. Pediatr Cardiol.
myocarditis. Pediatr Drugs. 2002;4:171-81. 2006;27:336-42.
31. Scholz TD, Reinking BE. Congenital heart disease. In: 35. Mevorach D, Elchalal U, Rein AJ. Prevention of complete
Gleason CA, Devaskar S, (eds). Avery’s Diseases of the heart block in children of mothers with anti-SSA/Ro and
Newborn. 9th edition. Philadelphia, Pa: Saunders Elsevier; Curr Opin Rheumatol. 2009;21:478-82.
2011,pp. 762-88. 36. Netz H, Bauer JJ, Scheld HH, et al. Cardiac Transplantation in
32. Chen SC, Balfour IC, Jureidini S. Clinical spectrum of restric a Neonate with Endocardial Fibroelastosis, Tex Heart Inst J.
tive cardiomyopathy in children. J Heart Lung Transplant. 1990;17:122-5.
2001;20:90-2. 37. Ino T, Benson LN, Freedom RM, et al. Natural history and
33. Rosenthal D, Chrisant MR, Edens E, et al. International Society prognostic risk factors in endocardial fibroelastosis. Am J
for Heart and Lung Transplantation: Practice guidelines Cardiol. 1988;62:431-44.
741
http://vip.persianss.ir
Sec t i on
10
http://vip.persianss.ir
C hapter
http://vip.persianss.ir
10 has served, in most cases, not only as the cardiologist, but EMPLOYABILITY
as the primary care provider. As the child grows, parents
need to be encouraged to identify a primary care physician Adults with CHD have been able to find comparatively steady
Congenital Heart Disease in Adults
(general physician) who assumes not only the responsibility employment, although the type of employment for some
of coordinating the care, but is also willing to work closely is inferior compared to the general population. Obtaining
with cardiology and other subspecialities.9 suitable employment has historically been a serious concern
Particular attention must be given when the patient requires for the young adult with CHD.17 While less so today, full-time
non-cardiac surgery.10,11 Perioperative safety can be assured or part-time employment has been reported to occur in only
if the risks inherent in each individual case are anticipated. 71 percent of adults with CHD as compared with 84 percent
The surgical team must be informed as to the relative risk of healthy people.15,18,19 The rate of employment tends to be
of operation, including risks of bleeding, hypotension, higher among those with milder and acyanotic forms of CHD.17
hypovolemia and infective endocarditis. Relative risk is One possible explanation for this high unemployment rate is the
dependent upon the type of defect and any residual effects misunderstanding and the lack of knowledge or misperception
of CHD including rhythm disturbances, ventricular failure, regarding CHD by employers with respect to the individual’s
acquired medical problems or comorbidities such as diabetes future health prospects. Over the years, legislation in many
or hypertension. Cyanotic CHD with or without pulmonary parts of the world has been enacted to reduce employment
vascular disease presents with the highest risk and should be discrimination of individuals with preexisting disabilities. It
carefully evaluated prior to any surgical procedure. is therefore important for health care providers to give career
For females, gynecologic and reproductive issues are the and vocational counseling that assists the patient in selecting a
leading non-cardiac health issues that health care providers career. This should combine not only personal interests, but is
must address. A number of gynecologic issues such as in keeping with clinical limitations that the young person with
menstrual complaints and contraception frequently present CHD might have.20,21 In this way, we may provide them with
in adolescents and require age appropriate counseling and skills that are appropriate for achieving occupational success.
referral.12
FINANCIAL COSTS OF HEALTH CARE AND
EDUCATION AND CAREER COUNSELING INSURABILITY
While early studies reported that CHD had a negative Access to specialized care for the adult with CHD is not
impact on school progress, later studies have demonstrated uniformly available in all parts of the world. Even in developed
that with early surgical intervention and improved countries, patients and their families often have to travel long-
medical management, patients have attained educational distances for specialized care and follow-up. While most
milestones similar to those of healthy peers.13-15 Recent countries have national health care systems that will provide
studies focusing on neurodevelopmental outcomes have care to this special population, many of these centers are not
reported that while the majority of the children have within the patients reach. In the United States (USA), access
normal intelligence, a subgroup have demonstrated slightly to health care requires some form of insurance coverage and
lower scores on standardized tests of cognitive ability insurability. Infants and children are either covered by their
and academic achievement than those for the general parents’ insurance carrier or by a state health care coverage.
population.16,17 Specifically, children with complex CHD For adults with CHD, lack of insurance is one of the major
such as d-transposition of the great arteries, hypoplastic barriers to long-term follow-up and therefore discussions with
left heart syndrome and other functional single-ventricle parents and adolescent must be introduced, while they are still
lesions have a higher incidence of problems with academic covered by the parents or before the child’s state heath care
performance, behavioral abnormalities, hyperactivity and coverage is terminated, which is usually at 21 years or at 26
the ability to perform executive functions such as visual- years for students.18,20,22 Patients with complex CHD, who are
motor integration.16 Despite these findings, today the often more at risk, should be directed to explore policies that
majority of young adults with CHD achieve educational tend to have fewer restrictions such as group policies obtained
goals similar to that of the general population and should be through their employment.
encouraged to believe that they will grow up to be healthy
and able to work. Career counseling and vocational guidance SEXUALITY AND REPRODUCTIVE ISSUES
should be offered in middle and high schools so that based
upon their intellectual abilities and interests, adolescents are Sexual maturity is a major developmental milestone of
encouraged to achieve higher education and skills necessary adolescence. For many adolescents with CHD, discussion
for employment in occupations that are manageable based surrounding issues of human sexuality and reproduction are
on their work capacity. often avoided or ‘postponed’ by the parent and provider.
746
As a result many patients enter adulthood with a series of Table 1
53
misconceptions and fears about their sexuality or their ability Informational needs for the young with congenital health disease
to conceive and bear children. There is limited emerging data
http://vip.persianss.ir
10 Exercise Counseling maturity of the teenager and her commitment to adhering to the
prescribed contraceptive choice. Although oral contraceptives
While the majority of available information on exercise are effective when used by teenagers, it is estimated that 13
Congenital Heart Disease in Adults
supports the benefits of exercise for children and adolescent percent of teen users between ages of 15 to 17 years will miss an
CHD patients, it is important to counsel this growing average of three pills per month.34 Similar results are reported
population on appropriate recreational activities. This topic for patches and vaginal rings.34 Long-term contraceptives,
is discussed in more detail in the chapter on exercise and such as, implantable devices or IUDs, are safe for use in
sports in CHD. As adolescents enter high school and look young patients and carry a higher level of compliance.
to participate in higher level or competitive sports, exercise Injectables which are also safe still require regular return
testing is helpful in gauging safety. Over the years, the visits thus placing a certain level of responsibility on the teen
American Heart Association and others have published to return to clinic. Additionally, depomedroxyprogesterone
recreational and sport recommendations for young persons acetate (PMPS), known as Depo Provera carries a risk of
with heart disease.30-32 These guidelines have been the osteoporosis associated with the amenorrhea that occurs in
basis for outlining activities allowances and recommended long-term users.35 Therefore, teen use should be carefully
workloads for a number of postoperative defects and can be monitored especially in females who are extremely thin,
helpful to guide competitive and recreational activities that suffer from anorexia nervosa or have a comorbidity of
are safe. chronic renal disease36
749
http://vip.persianss.ir
10 29. Cetta F, Graham LC, Lichlenberg RC, et al. Piercing and 34. Balassone ML. Risk of contraceptive discontinuation among
adolescents. J Adolesc Health Care. 1989;10:527-33.
tattooing in patients with congenital heart disease: Patient
and physician perspectives. Journal of Adolescent Health. 35. Cundy T, Evans M, Roberts H, et al. Bone density in women
Congenital Heart Disease in Adults
750
C hapter
Reema Chugh
http://vip.persianss.ir
10
who have access to healthcare, to survive into adulthood. slit-shaped tunnel-like defect in the atrial septum, residual from
While most individuals born with congenital heart defects are the fetal circulation, due to the failure of the primum and the
Congenital Heart Disease in aDults
diagnosed in infancy and childhood, some go undiagnosed secundum atrial septum to fuse postnatally, is often associated
until adulthood. Other than the exceptional case of an early with another defect of atrial morphogenesis called atrial
surgically ligated, isolated patent ductus arteriosus with no left septal aneurysm (ASA). An ASA may be associated with one
ventricular enlargement or dysfunction, all adults with CHD or multiple PFO in 50 to 85 percent of the cases. The ASA is
have postoperative residual and sequelae that need follow-up characterized by a redundant, undulating, interatrial membrane
throughout their lives. in the region of the fossa ovalis, with the diameter of the base
There has been organized global effort to integrate exceeding 15 mm and the amplitude of the interatrial septum
multidisciplinary services devoted to this special population. excursion up to 10 to 15 mm.7 Presence of a concomitant ASA
Many clinics/centers for Adult Congenital Heart Association increases the likelihood of thrombus formation on the left atrial
(ACHD) GUCH have sprouted around the world. The side of the aneurysm. Besides an ASA, the other proposed high-
International Society for Adults Congenital Heart Disease risk factors for cerebral embolic events associated with a PFO are
(ISACHD) has been instrumental in bringing together experts Eustachian valve anatomy favoring right-to-left shunt, presence
from all over the world (www.isachd.org). Over the past decade, of venous thrombus or hypercoagulable states. Both PFO and
the American College of Cardiology,1 European Society ASA are undetectable on physical examination (Table 1).
of Cardiology2 and the Canadian Cardiovascular Society Over the past two decades, the PFO has caught clinical
Consensus Conferences,3-6 published guidelines to establish interest for potentially contributing to paradoxical embolism,
standards of care for the adult with CHD. In the United States, especially in adults < 55 years old with cryptogenic stroke. In
the ACHA provides patient support and advocacy (www. most studies, the clinical diagnosis of paradoxical embolism
achaheart.org). Currently there are several professional and was presumptive and was based on the presence of a right-
patient-centered organizations assisting in the universal goal to to left shunt in the absence of a left-sided thromboembolic
improve quality of life and care of the adults with CHD. source. Its association with migraines is still open to question.
While there is a detailed discussion of embryology, The question also arose, whether transcatheter device closure
pathology, genetics, natural history, clinical presentation, of PFO really ‘shut the door’?8
diagnosis and management of individual defects in other In a multicenter European study with 581 patients who had
chapters of this book, the aim of this chapter is to provide an ischemic stroke, an association of recurrent stroke rate for
a concise overview regarding salient management issues patients with ASA and PFO was 15.2 percent compared with
encountered while caring for an adult with CHD. 4.2 percent in the absence of these 2 defects.9 A prospective
population-based study, Patent foramen ovale In Cryptogenic
DEFECT SPECIFIC MANAGEMENT Stroke Study (PICSS), suggested that after correction for age
ISSUES IN ADULTS WITH CHD and comorbidity, an isolated PFO was not an independent
risk factor for future cerebrovascular events in the general
population.10 Unfortunately, the patients in this study were
SHUNT LESIONS
not truly representative of the PFO patient population with
ischemic stroke. The quest for an answer to whether “to close
Patent Foramen Ovale or not to close” the PFO in adults with cryptogenic stroke
One of the most common indications for performing a younger than 55 years by a percutaneous device is still on. A
transesophageal echocardiogram is to rule out cardiac source recent randomized trial (Closure I) did not detect any benefit
of emboli in an adult patient with a cerebrovascular event of closure over medical treatment alone.11-13
(stroke or transient ischemic attack). Besides looking for an With respect to selection of antiplatelet versus
obvious intracavitary thrombus, clot in the left atrial appendage anticoagulant therapy, the data continues to be controversial.
or atheromas in the ascending limb of the aortic root or arch, In the Warfarin-Aspirin Recurrent Stroke Study (WARSS),
the cardiologist is expected to rule out the possibility of a 2,206 patients were randomized to aspirin or warfarin (INR
paradoxical embolus through an interatrial communication 1.4 to 2.8) with no significant benefit from either treatment
with a right-to-left shunt, such as a patent foramen ovale (PFO) at 2 years.14 The present opinion based on observational and
or an atrial septal defect with a bidirectional shunt or shunt randomized data from 9 studies that compared the medical
reversal. An adequate Valsalva maneuver is essential, while therapies is consistent and suggests that anticoagulants are
assessing the presence of a right-to-left shunt by an agitated superior to antiplatelets for preventing stroke recurrence.11,15
saline contrast study with transthoracic or transesophageal While the search for the optimal management continues,
echocardiogram. patients with large PFO, especially in the setting of an atrial
It is the most common CHD, with an autopsy–derived septal aneurysm, may receive low dose aspirin for primary
752 incidence for a probe-patent PFO of around 27 percent. This prevention of thromboembolic events.
54
table 1
Shunt lesions
Secundum atrial septal Prominent right ventricular Atrial arrhythmias Anomalous pulmonary
defect impulse Right heart failure venous return
Wide fixed splitting of S2 Pulmonary hypertension
Pulmonary ejection systolic Left ventricular dysfunction
murmur at left upper sternal Paradoxical embolism/stroke
edge
Accentuated P2
Ventricular septal defect Pansystolic murmur Infective endocarditis Atrial septal defects (ASDs)
Precordial thrill Pulmonary hypertension Aortic valve regurgitation
Accentuated P2 (in Left ventricular dysfunction Aortic root dilatation
pulmonary hypertension) Conduction defects
(heart block)
Aortic insufficiency
Tricuspid regurgitation
Patent ductus arteriosus Continuous ‘machinery’ Infective endocarditis/ Occurs in association with
murmur at the left upper endarteritis several congenital heart
sternal border with radiation Pulmonary hypertension defects
to the back Left ventricular heart failure Accounts for 10% of all
Aneurysmal congenital heart defect
Calcification (CHD)
Rupture
Adapted from Chugh, R Caring for the adult with congenital heart disease: management of common defects. Perm J. 2007 Spring;11(2):40-6.
Atrial Septal Defects for ASD closure. A sinus venosus defect with associated
anomalous pulmonary venous return is suspected, when there
One in six individuals born with an atrial septal defects (ASDs) is right heart enlargement in the absence of a clearly defined
is likely to be first diagnosed in adulthood. Palpitations due to interatrial shunt. Further evaluation with a transesophageal
atrial arrhythmias and dyspnea are the most common presenting echocardiogram is recommended in these cases and in all cases
symptoms. An ASD is a direct communication between the prior to ASD closure to rule out concomitant congenital heart
cavities of the atrial chambers that permits shunting of blood. defects. Possible reasons for clinical deterioration in adults with
Associated defects occur in nearly 30 percent of patients with unclosed ASD are listed in Box 1.
a secundum ASD (the most common form). Characteristic The consensus is to close defects in symptomatic patients
physical findings are a prominent right ventricular parasternal and in those with right heart enlargement. Percutaneous
lift, persistent or wide fixed splitting of the second heart sound transcatheter device closure is presently the method of choice
and a pulmonary systolic ejection murmur, at the left upper for defects within the fossa ovalis with an adequate rim
sternal edge due to increased pulmonary flow. Pulmonary of at least 4 to 5 mm (in order to avoid distortion of these
hypertension leads to an accentuation of the pulmonary surrounding structures), between the ASD and the aortic valve
component of the second heart sound. Electrocardiogram (ECG) annulus, atrioventricular (AV) valves, pulmonary and systemic
may show sinus rhythm or atrial fibrillation, right axis deviation veins. In the presence of pulmonary hypertension, the defect
(left axis deviation in primum ASD) and a bifid notch on the may be safely closed if pulmonary artery systolic pressure
ascending limb of the R wave in inferior leads (‘crochetage’).16 is less than 50 percent of the systemic arterial pressure.
Transthoracic echocardiography establishes the diagnosis in Right heart catheterization to assess the pulmonary vascular
most cases by demonstrating a discontinuity of the interatrial resistance may be required for those with higher pulmonary
septum on two-dimensional echocardiogram and an intracardiac artery pressures. In general, all defects should be considered
shunt at the atrial level with color Doppler. Long-standing for early closure unless there are specific contraindications.
significant left-to-right shunt causes right heart enlargement Endocarditis/endarteritis prophylaxis is recommended for 6 753
and elevated pulmonary artery pressures, which is an indication months after device closure.1
http://vip.persianss.ir
10
Box 1: Causes for clinical deterioration in adults Victor Eisenmenger in 1897 described a bidirectional or
reversed (right-to-left) shunt through the large VSD leading
Congenital Heart Disease in aDults
table 2
Valvular defects
Pulmonary regurgitation Widely split second heart sound Right heart enlargement Pulmonary valve abnormality-
(absent if rudimentary or absent Right heart failure isolated
valve tissue) Tetralogy of fallot
Crescendo-decrescendo, short
diastolic murmur—best heard in the
second or third intercostal space
Ebstein’s anomaly Widely split first heart sound, split Atrial arrhythmias- fibrillation/ PFO–very common
second heart sound, soft, early flutter—25–30% ASD–over 30%
systolic murmur that increases Supraventricular tachycardia Wolf-Parkinson-White
with inspiration— best heard at the Right heart failure syndrome—5–25%
lower left sternal border Left heart failure Congenitally corrected
Cyanosis transposition of the great
Sudden cardiac death arteries (CCTGA)
Paradoxical emboli VSD
Patent ductus arteriosus (PDA)
Left heart abnormalities
including left ventricular non-
compaction (LVNC)—40%
Pulmonary stenosis or atresia
Tetralogy of Fallot
Bicuspid aortic valve Systolic ejection click Infective endocarditis Coarctation of aorta
Early peaking systolic flow murmur Aortic dissection Aortic root dilatation
Aortic stenosis Sub and supra-aortic stenosis
Aortic insufficiency VSD
Mitral valve prolapse Apical mid to late systolic clicks Mitral regurgitation Secundum ASD
(MVP) Late systolic murmur with Atrial arrhythmias Holt-Oram syndrome
radiation to the apex due to mitral Endocarditis Ebstein’s anomaly
regurgitation MVP syndrome Marfan syndrome
Heart failure Ehlers-Danlos syndrome
Infective endocarditis Osteogenesis imperfecta
Syncope (related to orthostatic 755
hypotension)
Sudden cardiac death—rare
http://vip.persianss.ir
10
(25–49 mm Hg), moderate (50–79 mm Hg) and severe (over 80 enlargement occurs with long-standing severe pulmonary
mm Hg). In order to avoid adverse effects from long-standing regurgitation. The interventricular septum is dyskinetic due to
Congenital Heart Disease in aDults
significant PS, percutaneous balloon valvuloplasty should right heart volume overload and the left ventricle may appear
be performed, when the peak transvalvular gradient is over D-shaped on the parasternal short-axis view.
50 mm Hg, even when the patient is asymptomatic.22 Severe Pulmonary valve replacement is indicated in patients
PS can lead to marked right ventricular hypertrophy, right heart with severe pulmonary regurgitation, who are symptomatic
failure and risk of sudden cardiac death. Surgical valvotomy or have early signs of right heart enlargement with impaired
or pulmonary valve replacement is considered, when there is ventricular function.1
significant calcification, a thickened stiff dysplastic valve and/
or concomitant pulmonary artery aneurysm. Pulmonary valve CONGENITAL TRICUSPID VALVE DEFECTS
replacement (transcatheter or surgical) is indicated for severe
pulmonary regurgitation before it affects the right ventricular
Ebstein’s Anomaly
function.1
Ebstein’s anomaly is an abnormality of the tricuspid valve
Pulmonary Regurgitation characterized by the tethering of the septal leaflet to the
ventricular septum that gives an impression of apical
Clinically insignificant trace to mild pulmonary regurgitation displacement of the tricuspid valve. It is associated with
(PR) is seen in individuals with structurally normal hearts.23 discontinuity of the central fibrous body, which lends itself to
It rarely occurs as an isolated defect. Most adults present creating a substrate for accessory pathways and type B Wolf-
with significant PR in association with tetralogy of Fallot and Parkinson-White (WPW) syndrome in 5 to 25 percent of the
rarely with other malformations. Significant PR may occur in cases. These patients are therefore predisposed to having
the presence of morphologically abnormal pulmonary valves supraventricular tachycardia.25
or when there is total absence of the pulmonary valve. While On physical examination, the characteristic signs are a
most adults tolerate low pressure PR, a small group may palpable impulse in the left third intercostal space (due to an
develop right heart enlargement and right heart failure due to enlarged infundibulum). On auscultation, the first heart sound
long-standing severe PR.24 Pulmonary hypertension (primary is widely split due to a delayed loud tricuspid component
or secondary) can contribute to progression of PR. (caused by the increased excursion of the elongated anterior
Isolated PR is incidentally diagnosed because of the murmur, leaflet of the tricuspid leaflet that delays closure of the
in association with a dilated pulmonary trunk noted on a chest valve). In the presence of a right bundle branch block, the
X-ray or as an incidental finding on an echocardiogram. second heart sound is also split due to delayed closure of the
On clinical examination, patients with right heart failure pulmonary valve. A quadruple rhythm may be heard due to
will have prominent A and V waves of the jugular venous third and fourth heart sounds. There is a soft, early systolic
pulse. On palpation, in patients with severe PR, there is a murmur that increases with inspiration and is best heard at the
hyperdynamic pulse at the left sternal border and subxiphoid lower left sternal border.16
area. Dilated pulmonary artery may generate prominent The characteristic finding on the electrocardiogram of the
pulsations in the second left intercostal space. On auscultation, tall, peaked ‘Himalayan’ p waves (described by Dr Helen
a normal first heart sound is usually followed by a widely Taussig) occur primarily due to prolonged aberrant conduction
split second heart sound (usually associated with increase through the markedly enlarged right atrium.26 PR interval may
capacitance of the pulmonary vascular bed and slow elastic be prolonged in 50 percent of the cases except, when there
recoil) that decreases with inspiration in the absence of right is preexcitation (demonstrated by an intermittent delta wave)
heart failure. The second heart sound is absent, when there due to type B WPW syndrome in nearly 25 percent of the
is rudimentary or absent valve tissue. Patients with moderate cases. Additionally, there is right bundle branch block pattern
to severe PR have a distinctive crescendo-decrescendo, short and deep Q waves in the inferior leads, as well as in V1-4.25
diastolic murmur that is best heard in the second or third Chest X-ray is notable for a narrow vascular pedicle due to
intercostal space.16 lack of pulmonary artery border and a narrow ascending aortic
Two-dimensional echocardiogram defines the anatomy of shadow. A ‘box-like’ appearance of the cardiac silhouette is
the pulmonary valve, the size of the main pulmonary artery, due to a very prominent right atrial border contributing to the
proximal right and left branches, size and contractility of the right heart convexity and a dilated infundibulum contributing
right ventricle. Pulmonary regurgitation is primarily graded to left heart convexity.16
by color Doppler. An important point to note is that the right Echocardiogram defines the morphology of the tricuspid
ventricular outflow tract may have pulsatile motion in the case valve and allows assessment of the right atrial size, biventricular
of low pressure severe pulmonary regurgitation, even when size, function and associated defects (Table 3). The tricuspid
756 the color Doppler is not too impressive. Significant right heart valve is characterized by apical displacement due to tethering
54
table 3
Complex congenital heart defects
http://vip.persianss.ir
10
Contd...
Congenital Heart Disease in aDults
of the septal leaflet, over 2 cm in adults, in relation to the saturation with activity. Severe tricuspid regurgitation and
septal attachment of the mitral valve. In contrast, the anterior increased degree of apical displacement of the tricuspid valve
leaflet appears elongated and large with ‘sail-like’ motion. The predisposes to right heart failure. Eventually, left heart failure
right atrial size appears larger due to ‘atrialization’ of the right may develop due to prolonged cyanosis, interventricular
ventricle, with relatively small right ventricle. Color Doppler dependence and left heart fibrosis.
is used to assess the severity of tricuspid regurgitation and Cyanosis occurs, when high filling pressures of the volume-
rule out an interatrial communication such as a patent foramen overloaded right ventricle instigate right-to-left shunting at the
ovale or an atrial septal defect. atrial level. These patients are at risk for paradoxical emboli
Clinical presentation in adults with Ebstein’s anomaly or cerebral abscess because of the interatrial communication
depends upon the severity of morphological tricuspid valve (PFO or ASD). Atypical chest pain, the etiology of which is
abnormality, the functional status (degree of regurgitation) not clearly understood, but sometimes attributed to sternal
of the tricuspid valve and the presence of associated defects. compression of the enlarged right heart, is also seen in some.
Adults with mild abnormality of the tricuspid valve with no Uncontrolled arrhythmias cause hemodynamic deterioration,
associated defects may remain asymptomatic for most of progressive cyanosis and syncope. The risk of sudden
their lives. The most common clinical issues in adulthood cardiac death may be increased by sustained tachycardias
are atrial arrhythmias such as atrial fibrillation/flutter and such as atrial fibrillation/flutter with rapid ventricular rates.
supraventricular tachycardia. Dyspnea and decreased exercise Atrial arrhythmias should be managed with medications.
758 tolerance occurs due to an inadequate increase in pulmonary Radiofrequency ablation (RFA) should be considered when
blood flow and a decrease in systemic arterial oxygen there is an accessory pathway, even though it is associated
54
with relatively low success rates.27 Right heart catheterization Although aortic root dilatation is most commonly associated
should be avoided since stimulation of the atrialized right with Marfan’s syndrome, in absolute numbers there are more
http://vip.persianss.ir
10
potassium and magnesium intake. Significant orthostatic Hence, closure of ASD will help reduce pulmonary blood
hypotension in the absence of heart failure, may respond to flow and the risk of developing pulmonary hypertension.
Congenital Heart Disease in aDults
volume expansion with good hydration, high sodium intake Echocardiography defines the morphological defect, left
and the use of fludrocortisone acetate (Florinef USP). It is tip mobility, papillary muscle anatomy and examines for
a synthetic adrenocortical steroid, which produces marked presence of a supravalvular fibrous membrane. The severity
sodium retention and increased urinary potassium excretion, of mitral stenosis is assessed by pressure half-time based
because of its mineralocorticoid effects. This leads to a rise in calculation of valve area, mean gradient and estimated of
blood pressure, because of the effects on electrolyte levels. It the right ventricular systolic pressure that is a surrogate
is usually prescribed as a daily oral dose of 0.1 mg. for pulmonary artery pressures. In double orifice valve or
On physical examination, although apical mid to late supravalvular membrane with multiple orifices, the area of the
systolic clicks (due to sudden tension in the subvalvular individual orifices is added to give a total orifice area. Medical
apparatus when the leaflets prolapse) have been reported, the management includes diuretics, beta blockers and arrhythmia
more frequent auscultatory findings are a late systolic murmur control. In case of severe symptomatic stenosis, surgery is
with radiation to the apex due to mitral regurgitation. ECG may performed.33
demonstrate nonspecific ST and T wave abnormalities that can
cause false positive treadmill stress tests. Two-dimensional Coarctation of Aorta
or three-dimensional, transthoracic or transesophageal echo-
cardiography are the most accurate diagnostic methods.32 While moderate to severe coarctation of aorta (COA) is
Afterload reduction with angiotensin converting enzyme usually diagnosed in infancy or childhood, the diagnosis is
(ACE) inhibitors or angiotensin receptor blockers is suspected in a person presenting with secondary hypertension
recommended in hypertensive adults with mitral regurgitation. in adulthood. Severe left ventricular hypertrophy by voltage
Mitral valve repair should be considered early in symptomatic criteria on an electrocardiogram or by echocardiographic
patients with preserved left ventricular size and function. criteria in a young adult should raise an alarm.
Although mitral valve replacement is less desirable, it Coarctation of aorta is congenital narrowing of the aorta at
may be the only option for those with very friable, heavily the junction of the distal aortic arch and the descending aorta,
myxomatous valves with severe prolapse. below the origin of the left subclavian artery. It comprises up to
8 percent of all CHD. The discrete coarctation is not just limited
Cleft Mitral Valve to focal stenosis, but is one variant of a diffuse arteriopathy and
associated structural abnormalities of the great arterial walls.16
Besides MVP, congenital MR may occur in association with A brachial and femoral blood pressure recording demonstrates
a cleft mitral valve, usually seen in association with Down upper-body arterial hypertension. There are decreased arterial
syndrome or rarely as an isolated defect. The management pulsations and blood pressure in the left upper extremity when
in adults with mitral regurgitation is guided by the criteria there is interrupted blood flow into the left subclavian artery
outlined for acquired mitral regurgitation.33 (with compensatory blood flow via collaterals). Accurate
blood pressure recordings are obtained from the right arm in
Congenital Mitral Stenosis these individuals. Characteristic physical findings are weak,
delayed femoral pulses, prominent left ventricular impulse,
A diverse group of congenital mitral valve anomalies can a loud aortic closure sound, thrill in the suprasternal notch
cause obstruction to left atrial flow and that leads to mitral and vascular murmur between the shoulder blades beginning
stenosis. Although rare in adults, the diagnosis is confirmed in mid systole and persisting beyond the second heart sound.
by transthoracic or transesophageal echocardiogram. Continuous murmurs due to collaterals may be present.
Most adults have had mitral valve replacement, since the Echocardiography demonstrates the gradient across the
severe cases are usually diagnosed in childhood. It is rare aortic arch and defines the commonly associated defects -
for an adult to present with Shone’s complex, characterized bicuspid aortic valve in 75 to 85 percent of the cases, aortic
by a supravalvular membrane or ring, parachute mitral root dilatation/aneurysm, VSD, mitral valve abnormalities
valve, subaortic stenosis and coarctation of aorta.16 Usually (Table 3) and allows assessment of left ventricular mass
presenting as a stable lesion, the supravalvular mitral ring and function. MRI is useful for delineating aneurysms in
may also be seen in association with a VSD, PDA, AV septal postoperative cases and also shows site of the stenosis, the
defects or double outlet right ventricle (DORV). extent and degree of narrowing, pressure gradient across the
Clinical presentation is similar to rheumatic mitral stenosis, stenosis, aortic arch anatomy, and aortopulmonary collaterals.
with the additive effect from associated defects. When Patients with COA are at increased risk for aortic
congenital MS occurs in association with an ASD, there may aneurysms and dissection. Hypertension often persists after
760 be an increase in left atrial pressure and left-to-right shunt. surgery and ambulatory blood pressure monitoring may
54
detect uncontrolled hypertension in those, who appear to
be normotensive at rest during office visits. Adequate blood Box 2: surgeries for tetralogy of Fallot
http://vip.persianss.ir
10
• Endocarditis 10 to 15 years, cardiologists often try to minimize the number
• Paradoxical thrombo-embolism through interatrial right- of surgeries required in a lifetime by appropriately timing and
Congenital Heart Disease in aDults
762
Figure 1: ECG in a 43-year-old man with tetralogy of Fallot showing right bundle branch block (RBBB).
The QRS duration should be followed-up on serial electrocardiograms
54
Holter test and/or treadmill stress testing should be requested as seen with Marfan syndrome, bicuspid aortic valve and
in a patient presenting with palpitations or presyncope, since coarctation of aorta. It is not uncommon to see patients remain
http://vip.persianss.ir
10
The oxygenated blood returning from the lungs passes through to keep up with the increasing blood supply requirements,
the pulmonary veins, via another baffle into the right ventricle leading to perfusion defects. Progressive systemic AV
Congenital Heart Disease in aDults
that pumps the blood through the aorta into the systemic (tricuspid) valve regurgitation behaves in a similar way like
circulation. Hence, the morphological right ventricle is the mitral regurgitation affects a structurally normal heart.50-52
systemic ventricle and the morphological left ventricle is the
subpulmonic ventricle. Systemic AV Valve Regurgitation
The major difference between the Senning and the Mustard (Tricuspid Regurgitation)
operations is the material used for the baffle. In the Senning There is an increased predisposition for systemic AV valve
operation, the baffle is created from the patient’s tissues regurgitation, due to the altered geometry of the systemic right
(right atrial wall and part of the atrial septum).47 The Mustard ventricle in D TGA. The tricuspid annular dilatation, globular
operation uses pericardium and synthetic material to make the shape of the enlarging right ventricle and displaced chordal
baffle.48 attachments of the systemic AV valve leads to progressive
The long-term residua and sequelae experienced by the regurgitation. The systemic AV valve regurgitation then
patient’s, who underwent an atrial switch operation are listed leads to further right ventricular enlargement and worsening
in Table 4. Most common causes of morbidity and mortality in systemic RV function.
this population are heart failure due to progressive impairment
of systemic right ventricular, not designed to withstand the Baffle Problems—Obstruction or Leaks
pressure load of lifelong pumping into the systemic circulation. Baffle leaks usually occur along suture lines and most
Most patients demonstrate decreasing systemic ventricular commonly along the superior limb of the systemic venous
function by the second to third decade of life. Bradyarrhythmias baffle, in 25 percent of the individuals, who have undergone
due to chronotropic incompetence from sick sinus syndrome atrial switch repair. Fortunately, not all leaks are clinically
and atrial arrhthymias related to atrial surgical incisions and significant. A left-to-right shunt through the baffle leak is
baffle construction affect many young adults. hemodyamically more significant, when it has the potential
for volume overloading of the systemic ventricle. Right-
Rastelli Repair to-left shunts are clinically more significant if they are
contributing to worsening systemic arterial oxygenation and
Dr Rastelli, at the Mayo Clinic described this surgery in cyanosis.
1969.49 In patients with D TGA and pulmonary outflow tract Obstruction of the superior limb of the systemic venous
obstruction who have a large, subaortic VSD, a Rastelli repair Mustard baffle is more common (5–10%) than that of the
is performed utilizing a conduit to direct the blood from the inferior limb (1–2%). Pulmonary venous baffle obstruction
right ventricle (via the VSD) to the aorta. The blood from the may occur in around 2 percent of the cases. Transesophageal-
left ventricle is directed to the aorta thereby making the left guided transcatheter intervention with stent implantation may
ventricle the systemic ventricle. These patients are relieved relieve the obstruction in most cases. In other cases of severe
of the long-term issues related to atrial repair, but may need obstruction, surgical correction may be needed.
further re-operations for the conduit.
While a Rastelli repair in early infancy protects from Arrhythmias
prolonged cyanosis, the infant-sized conduit needs more re- Bradyarrhythmias—Resting sinus bradycardia with a slow
operations for replacement over a lifetime. Biventricular junctional escape rhythm is common with progressive
dysfunction may occur due to long-standing conduit obstruction sinus node dysfunction occurring in 50 percent of patients
or volume overload. Long-term issues in the postsurgical postoperatively over time. Many patients will need pacemakers
patient with D TGA and Rastelli repair are listed in Table 3. after their third decade of life.
Tachyarrhythmias—Incisional atrial re-entry tachycardia
Long-term Issues with Atrial Switch Repair (atypical atrial flutter) occurs in 50 percent of the adults post
atrial switch repair (Figures 2A and B). Electrophysiological
Systemic Ventricular Dysfunction and Heart Failure studies and radio frequency ablation (RFA) may help 75
The right ventricle is unable to keep up with the demands of percent of the patients, but the incidence of high grade AV
pumping into the systemic circulation long-term and begins to block requiring a pacermaker is very high.53-55
deteriorate in the third decade of life. The degree of deterioration
is multifactorial, but primarily depends on the right ventricular Pulmonary Vascular Disease
morphology and demand-supply mismatch from right Pulmonary hypertension is more common in patients who
ventricular hypertrophy. The right coronary artery is unable have long-standing shunts and underwent late repairs.
764
54
B
Figures 2a and B: Serial electrocardiograms in a 35-year-old woman with d-transposition of the great arteries postatrial switch repair
(Mustard operation) showing atrial flutter. The hidden flutter waves are revealed as the rate slows down
http://vip.persianss.ir
10
Delay in performing this surgery may result in long-term Unfortunately on echocardiography, it is not too uncommon
left ventricular failure, since there is disuse atrophy of the for the systemic AV valve to be mistaken, as the mitral valve
Congenital Heart Disease in aDults
subpulmonic left ventricle due to low pressure load. In this in an undiagnosed case of CCTGA. At times, an embarrassing
operation, the aorta and the pulmonary artery are transected situation may occur when a cardiac surgeon opens the chest
at the level above the coronary sinus and the coronaries are to operate on the mitral valve and is shocked to find the
dissected from the aortic sinuses with a ‘button’ of tissue around morphological tricuspid valve on the left side of the heart. If
them and sutured into the neo-aorta. The main pulmonary there is no CHD surgeon available to help out, he/she may
artery is repositioned anterior to the neo-aorta and the two end up closing the chest without performing the surgery. The
great arteries are sutured into their anatomically corrected patient in this situation is so emotionally traumatized for
positions. The most important feature of this operation is that having undergone an unfruitful open-heart surgery that he/
it allows the left ventricle to function as the systemic ventricle, she may refuse to undergo another surgery to fix the severely
thereby reducing the risk of early morbidity or mortality from regurgitating AV valve.
systemic ventricular dysfunction and heart failure. Long-term While reading echocardiograms one must look carefully
outcomes are reviewed in Table 3.57 Coronary arterial fibrosis at the morphology of the ventricles. The AV valves follow
leading to potential ischemia appears to be the major long- their respective ventricle, hence the systemic AV valve
term issue in this population.58 (morphologic tricuspid valve) that is more apically placed
than the mitral valve (Figure 4) is on the same side of the heart
Congenitally Corrected Transposition of the as the right ventricle.
Great Arteries Standard heart failure management is recommended with
the use of carvedilol, ACE I/ARB and aldactone titrated to
Patients with congenitally corrected transposition of the maximum tolerated dose. Digoxin may be added if tolerated.
great arteries (CCTGA) with no associated defects may go Exercise training has miraculous effects on cardiovascular
undiagnosed into adulthood. They most commonly present conditioning in disciplined individuals, who can persistently
with heart failure when the morphological right ventricle, perform at least 45 minutes of daily aerobic activities. Surgical
which is the systemic ventricle, begins to fail. Nearly 25 percent management and the role systemic AV valve surgery are
patients develop heart failure by 45 years of age.59 Although discussed in the chapter on congenitally corrected transposition
the atria are in the normal position, there is double discordance of the great arteries.
with transposition of the great arteries, and ventricular
inversion. Although these two wrongs try to make a right by Univentricular Heart (Single Ventricle Physiology)
attempting to establish a physiologically correct circulation, with Fontan Operation
the major caveat is that the morphologically right ventricle
functions as the systemic ventricle, and pumps into the aorta. In 1971, Dr Francois Fontan performed a new surgical
The blood from the superior and inferior vena cavae flows procedure in patients with tricuspid atresia that would be
into the right atrium that drains into the left ventricle through later become known as the classic Fontan operation. The
the morphological mitral valve. The left ventricle pumps the goal of this surgery is to improve blood flow to the lungs
blood into the pulmonary artery. The oxygenated blood returns by connecting the right atrium to the pulmonary artery.63
from the lungs returns via the pulmonary veins into the left Tricuspid atresia is the commonest form of atrioventricular
atrium and then flows through the morphological tricuspid atresia with complete absence of the tricuspid valve or
valve into the morphological right ventricle which pumps into imperforate tricuspid tissue. Majority of the cases have a
the aorta. Associated defects lead to varying presentations concordant ventriculoarterial connection, while in nearly one-
and diagnosis is usually made early in life. Cyanosis may be third cases there is transposition of the great arteries. There
seen in patients with significant left ventricular outflow tract may be a restrictive VSD connecting the left ventricle to the
(LVOT) obstruction associated with a VSD. Other long-term hypolastic right ventricle.
residua and sequelae are reviewed in Table 3. Some patients have to undergo palliative surgeries in
On physical examination, there is usually a loud single childhood, such as a bidirectional Glenn to improve pulmonary
second heart sound (A2). Sometimes a soft P2 may be heard. blood flow (especially in the setting of severe pulmonary
Patients with systemic AV valve regurgitation will have a systolic stenosis) and then later have a conversion to the Fontan
murmur at the left sternal border or apex. Other murmurs may be operation to improve oxygenation.64 Although, cyanotic
audible depending upon the associated defects. An adult with no patients become acyanotic and have improved quality of life
associated defects/signs of heart failure may go undiagnosed. and longevity after the Fontan operation, there are long-term
The ECG is often misinterpreted as showing a previous issues such as progressive ventricular dysfunction, atrial
myocardial infarction, because there are Q waves in the arrhythmias, recurrence of cyanosis, elevated pulmonary
766 anterior leads due to ventricular inversion60 (Figure 3). vascular resistance and protein-losing enteropathy, which
Coronary artery anatomy is also inverted.61,62 can result in heart failure, thromboembolism and stroke. The
54
Arrhythmias
There is higher probability of atrial arrhythmias in patients
Figure 4: Transthoracic echocardiogram in the apical four-chamber
with a classic Fontan due to markedly enlarged right atrium
view showing crux anatomy. Note that the tricuspid valve (apically
displaced) is on the left side along with the morphological right ventricle and higher atrial pressures. In addition, mitral/systemic
(with the prominent moderator band). LA = Left atrium; LV = Left atrioventricular valve regurgitation predisposes to left atrial
ventricle; MV = Mitral valve; MB = Moderator band; RA = Right atrium; enlargement and atrial fibrillation. Suture lines in the atria from
RV = Right ventricle; TV = Tricuspid valve;
prior surgeries may be also trigger arrhythmias. Medications
such as beta blockers or calcium channel blockers, with
recurrence of cyanosis may be due to fenestrated atrial septum, or without digoxin are used for rate control. Amiodarone is
pulmonary arteriovenous fistulae and other causes. Many the antiarrhythmic of choice, when atrial fibrillation/flutter
patients may also need revision of the Fontan operation. Over persists. The lowest dose should be used and it should be
the years, the Fontan operation has undergone modifications carefully monitored for adverse pulmonary effects, thyroid and 767
with the total cavopulmonary connection (TCPC) achieved liver function tests.
http://vip.persianss.ir
10
Sometime intractable arrhythmias are a sign of a failing enteropathy (PLE) by 10 years was 13.4 percent and 5-year
Fontan. In these cases a revision of the Fontan or relief of the survival after the diagnosis was 46 percent. Hemodynamic
Congenital Heart Disease in aDults
conduit obstruction is indicated. Electrophysiology assessment data showed an increased systemic venous pressure, decreased
is indicated, when poorly controlled arrhythmias cause further cardiac index, increased pulmonary vascular resistance and
deterioration of the hemodynamics. Unfortunately, lateral increased ventricular end-diastolic pressure. Factors related
and extracardiac conduits limit catheter access for ablating to PLE were ventricular anatomy, increased preoperative
arrhythmias even though the likelihood of arrhythmias in these ventricular end-diastolic pressure, longer operative bypass time,
patients is expected to be lower than in the classic Fontan. increased length of hospital stay and postoperative renal failure.
Intra-atrial re-entrant tachycardia (atypical atrial flutter) is Patient selection and perioperative factors seem to predispose
common and often difficult to treat. to PLE.65 The management options are limited and primarily
supportive. These include a special diet, unfractionated
Heart Failure heparin, corticosteroids and somatostatin analogs. Some
patients benefit from decreased systemic venous pressure and
Management of ventricular dysfunction is challenging. passive hepatic congestion by transcatheter fenestration of the
Afterload reduction/vasodilators may not be well-tolerated in atrial septum. Fontan revision and heart transplantation have
the Fontan patient. sometimes showed temporary improvement of the protein
losing enteropathy.
Antiplatelet Versus Anticoagulation Therapy
Endocarditis Prophylaxis
Classic Fontan puts patients at a very high-risk for thrombus
formation (Figure 5). The role of antiplatelet versus Appropriate dose of antibiotics is advised for endocarditis
anticoagulation therapy remains controversial and needs to be prophylaxis in all Fontan patients.
individualized.
CONCLUSION
Protein-losing Enteropathy
Long-term follow-up and appropriate management are essential
This is the most serious complication post Fontan characterized to ensure improved quality of life and longevity in adults with
by increasing ascites, edema, pleural effusions and malnutrition. CHD. Antibiotic prophylaxis for bacterial endocarditis should
The diagnosis is confirmed by low serum albumin levels and be prescribed when indicated, especially in high-risk patients
increased fetal alpha antitrypsin. Feldt et al. showed that with complex CHD, conduits, pacemakers, defibrillators,
the cumulative risk for the development of protein-losing previous history of endocarditis and most importantly in those
with a bicuspid aortic valve or a ventricular septal defect.66
Echocardiography is the primary imaging tool for follow-up of
these adults.67 In addition to echocardiography, CT/MRI may
be required for monitoring the aorta in adults with BAV, COA
and other conditions that lead to aortic aneurysm, according
to the guidelines for management of thoracic aortic disease.68
The threshold for follow-up and surgery is 5 mm lower than
in general population. All the American Heart Association
guidelines can be downloaded for free in the PDF format
from the internet for up-to-date reference. A multidisciplinary
approach is required to provide complete care for multiple
issues including exercise/sports, mental health, obstetric and
gynecological care discussed in other chapters of this book.
REFERENCES
Figure 5: Transesophageal echocardiogram confirming a right atrial 1. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA
768 thrombus in a 38-year-old woman with tricuspid atresia with history of a 2008 guidelines for the management of adults with congenital
classic Fontan operation (right atrium to pulmonary artery connection) heart disease: a report of the American College of Cardiology/
54
American Heart Association Task Force on Practice Guidelines. foramen ovale in prevention of recurrent neurological events
J Am Coll Cardiol. 2008;52(23):e143-263 or in Circulation. after presumed paradoxical embolism. JACC Cardiovasc
http://vip.persianss.ir
10
34. Oliver JM, Gallego P, Gonzalez A, et al. Risk factors for aortic 51. Millane T, Bernard EJ, Jaegii E, et al. Role of ischemia and
complications in adults with coarctation of the aorta. J Am Coll infarction in later right ventricular dysfunction after atrial
Congenital Heart Disease in aDults
Reema Chugh
http://vip.persianss.ir
10
normal. All the major clinical manifestations are a result
Greek polys, ‘many’) and the designation is not appropriate
of exposure of multiple organs to prolonged chronic
Congenital Heart Disease in Adults
Table 1
Multiorgan manifestations of cyanotic congenital heart disease
http://vip.persianss.ir
10
therapy is well tolerated and the patient completes the course, interferes with the production of DNA precursors required
the benefits include a significant increase in iron stores, mean for cell replication and maturation. The treatment must be
Congenital Heart Disease in Adults
corpuscular volume (MCV) and hemoglobin concentration guided by a hematologist and reserved for selected cases of
within 3 months. There is also an increase in exercise capacity refractory hyperviscosity syndrome. In these cases, despite all
and an improvement in quality of life. measures, including iron repletion, the symptomatic patients
Phlebotomy: The age old practice of phlebotomy has a continue to have high hematocrits and are at increased risk for
very limited role now and can be detrimental in most cases. adverse events. Potential serious side effects associated with
The indications for therapeutic phlebotomy in patients hydroxyurea treatment are neutropenia and thrombocytopenia
with polycythemia rubra vera cannot be applied to patients that usually resolve when the treatment is stopped.11
with cyanotic CHD as these two disorders have completely
different pathophysiology. Unfortunately, this fundamental Hemostatic Abnormalities
misconception caused too many inappropriate and often
harmful phlebotomies in cyanotic CHD patients for several Cyanotic CHD patients are vulnerable to bleeding that may vary
years. Phlebotomies have sometimes been fatal and at other from mild to serious and sometimes fatal bleeding. Epistaxis,
times exacerbated hyperviscosity syndrome by causing bruising, petechial and gingival bleeding are examples of mild
more sludging in the microcapillaries, by the iron deficient bleeding. Bleeding associated with trauma or surgery can
microspherocytes. be serious. Hemoptysis can be minor to fatal. Many factors
Phlebotomy should only be considered in an iron replenished associated with bleeding tendency include erythrocytosis with
patient, if the hematocrit continues to remain above 65 and hematocrit over 65 percent, thrombocytopenia, shortened
there are persistent symptoms of the hyperviscosity syndrome, platelet lifespan, clotting factor deficiencies and abnormal
even after receiving adequate hydration. prothrombin time.12,13 Some patients may have congenital
Phlebotomy should be performed with utmost care hematologic disorders (such as in von Willebrand disease)
only when it is strongly indicated.4,5 In the absence of iron associated with CHD.12
deficiency or dehydration, the main indications are: During cardiac surgery many patients will have excessive
a. Persistence hyperviscosity symptoms when the bleeding due to further reduction in platelet counts and
hematocrit is above 65 percent despite adequate function. Coagulation factor deficiencies, heparin-induced
hydration. thrombocytopenia, disseminated intravascular coagulation,
b. Preoperative phlebotomy if the hematocrit is above excessive fibrinolysis may also be contributing factors.
65 percent despite adequate hydration, for reducing Clinically, all patients with cyanotic CHD should avoid
perioperative bleeding complications and/or for saving taking antiplatelet agents such as clopidogrel, Aspirin and other
autologous blood for potential transfusions. nonsteroidal anti-inflammatory drugs (NSAIDs). They should
Phlebotomy is performed as an outpatient procedure, also avoid anticoagulation with low molecular weight heparin or
with admission to an observation unit with cardiac and non- warfarin as far as possible. When warfarin is strongly indicated
invasive hemodynamic monitoring. The following protocol is for persistent atrial fibrillation, the presence of a mechanical
recommended: prosthetic valve, deep vein thrombosis or pulmonary embolus,
• Continuous cardiac electrocardiographic monitoring careful monitoring should be done to maintain the International
• Blood pressure, pulse rate and pulse oximetry checks every Normalized Ratio (INR) between 2 and 2.5.
15 minutes When bleeding occurs, fresh frozen plasma and vitamin
• Remove no more than 1 pint of blood slowly and replete K (for patients taking warfarin) may help. Appropriate
with equal or more volume of isotonic saline management of the cause, platelet transfusion, repletion of
• Observe for 4 hours and reassess symptoms any deficient factors may also be required. Desmopressin may
• Observe for improvement in symptoms help in some situations especially in raising von Willebrand
• Assess for orthostatic hypotension before discharging the factor concentrations. Platelet transfusions, fresh frozen
patient. plasma, vitamin K, cryoprecipitate and desmopressin can be
When performed appropriately and carefully, phlebotomy used to treat severe bleeding.12
should result in favorable clinical effects within 24 hours by
improving the stroke volume, the systemic blood flow and Cardiovascular Issues
the oxygen transport in these patients. The primary goal of
phlebotomy is to provide temporary relief from moderate to Hypoxemic erythrocytotic residents of high altitudes lack
severe symptoms of hyperviscosity syndrome. coronary atherosclerosis and have low cholesterol levels.
Use of hydroxyurea in hyperviscosity syndrome: Hydroxyurea It was postulated that hypoxemic erythrocytotic adults with
cyanotic congenital heart disease might be analogous.
(hydroxycarbamide) is an S-phase specific chemotherapeutic
774 Joseph K Perloff
agent that inhibits ribonucleotide reductase, and thus
55
Prolonged cyanosis and erythocytosis may have an shunt. Other situations with lower benefits from oxygen
unusual effect on the coronary circulation. While coronary supplementation in cyanotic CHD are fixed pulmonary
http://vip.persianss.ir
10
CHD patients often experience presyncope or syncope due herniation) or intravenous mannitol (for severe brain edema).
to inappropriate vasodilatation of systemic vascular bed. It Some patients may require interventions such as aspiration of
Congenital Heart Disease in Adults
probably occurs because of the increased nitric oxide levels the abscess24 and placement of a ventriculostomy catheter for
may play a central role in regulating vascular tone. In addition cerebrospinal fluid drainage, to relieve intracranial pressure
to adequate hydration, these patients should avoid hot showers and/or abscess excision.27 Seizures are a frequent complication
or prolonged exposure to hot weather. of brain abscess and anticonvulsants may be needed.27
Bacterial endocarditis prophylaxis and early detection
Stroke and treatment may prevent high morbidity and mortality
associated with brain abscesses.
The residents of high altitudes with secondary erythrocytosis
do not have a high incidence of stroke. However, strokes are a Cerebral Arterial Thrombosis
major cause of morbidity in cyanotic CHD population even in
the absence of classical cardiovascular risk factors. In patients For many years, adults with cyanotic CHD were inappropriately
with cyanotic CHD lesions, the prevalence of stroke is over phlebotomized for elevated hematocrit levels because of an
10-fold above the average.22 assumed risk of cerebral arterial thrombotic stroke caused
Most episodes appeared to be embolic and usually occur by hyperviscosity/sludging. Although the cerebrovascular
in cyanotic CHD patients with or without Eisenmenger accidents due to thromboses of the intracranial venous sinuses
syndrome. Cerebral hemorrhage may be precipitated by and veins have been associated with iron deficient secondary
problems with hemostasis or the use of anticoagulant therapy. erythrocytosis in children,4 there is no established correlation
between secondary erythrocytosis and cerebral arterial
Paradoxical Emboli thrombotic stroke in adults.28
In other studies, the reported incidence of strokes
Cyanotic CHD predisposes to an increased risk of stroke that in cyanotic CHD was up to 14 percent.29,30 Microcytic
may occur due to paradoxical emboli. Passage of thrombotic spherocytes caused by iron deficiency remains the strongest
or particulate matter can occur from the pulmonary to independent predictor for cerebrovascular accidents, even
systemic circulation (cerebral circulation), without allowing when patients with the two other strong independent risk
the blood to filter through the lungs. This risk can be reduced factors are excluded—hypertension and atrial fibrillation.30
by implementing prophylactic measures against deep venous Therefore, inappropriate phlebotomies should be avoided
thrombosis (DVT) and by introducing air filters in all since they exacerbate iron deficiency, which then leads to
intravenous lines. an increased risk of stroke in cyanotic patients.
http://vip.persianss.ir
10
the forearms and legs. They may also have pains in the distal bacterial endocarditis, since they have fragile spongy gums
ends of the metacarpals and metatarsals. Joint aches may be that bleed readily predisposing to bacteremia. Reducing the
Congenital Heart Disease in Adults
accompanied with local tenderness. These symptoms are due risk of gingivitis by taking excellent care of gums can reduce
to hypertrophic osteoarthropathy seen in more than 30 percent this daily and ongoing risk.
of the patients with cyanotic CHD. Meticulous daily dental care and biannual dental hygiene
In hypertrophic osteoarthropathy, there appears to be a visits are strongly advocated in all individuals with cyanotic
chronic inflammatory process with active bone metabolism. CHD. In addition, bacterial endocarditis prophylaxis should
There is edema, round cell infiltration with lifting of the be prescribed in all cyanotic CHD patients, since endocarditis
periosteum and involvement of the structures in the joint is associated with the most detrimental outcomes in this
capsule with adjoining soft tissue. The vascular endothelial population.49 Dental procedures should be avoided for 6
growth factor appears to play a role in addition to other months after an operation, since endothelialization of the
circulating growth factors that are normally inactivated in the prosthetic structures (such as valves, conduits) or sutures
lungs.43 Bisphosphonates are generally effective for relieving needs to be complete in order to reduce the risk of seeding the
pain related to hypertrophic osteoarthropathy, when the pain surgical site with bacteria.
is disabling and refractory to conventional analgesics.44
Skin and Nail Care
Scoliosis
Skin is the largest and most vulnerable organ of the body. Cuts
Scoliosis occurs more frequently in patients with CHD. and wounds are portals for bacteremia, if they are not cleansed
The impact of cardiac surgery on possibility of developing immediately with soap and water following an injury. Careful
scoliosis was reviewed in 998 patients with congenital heart follow-up and appropriate wound care are essential to avoid
defects who were below the age of 16 years. In this Mayo cellulitis and abscess formation. Acne frequently affects the
clinic study, there was no correlation between scoliosis and young people with skin lesions on the face, neck and shoulders.
the presence of cyanosis probably because of early surgical These patients are advised to avoid picking on the ‘pimples’
correction of cyanosis.45 and follow good skin hygiene, hydration, reduced caffeine
intake, stress management, get adequate sleep and take
Pregnancy, contraceptive and medications recommended by dermatology. Body piercing,
gynecological issues tattoos and intravenous drug use are strongly discouraged.
Nail biting or picking adjacent soft tissues is another
Cyanosis is a recognized high risk factor to fetal growth and common habit that opens up portals for bacteremia, besides
development and impacts outcomes in pregnancy. There is being socially unappealing. I have always enjoyed Dr Perloff
increased maternal and fetal mortality that correlates with advising nail-biters to dip their fingers in hydrogen peroxide
the degree of cyanosis, impaired ventricular function and solution from time to time during the day, since it is not only
pulmonary artery pressures.46 Adverse fetal outcomes include a potent disinfectant but also tastes terrible!
fetal wastage (high incidence of miscarriages), preterm
delivery and intrauterine growth retardation. Health Passport and Medical Records
The use of contraceptives is important in avoiding high
risk and unplanned pregnancies in these women. Appropriate The health passport and carrying essential medical records is
guidance regarding choice of contraceptives is important, even more essential in patients with cyanotic CHD, especially
since estrogen increases the risk of thrombosis. Reproductive when they are traveling outside the vicinity of their home
issues including menstrual disorders and infertility challenge town. The details about the health passport are discussed in
most women with cyanotic CHD.47,48 the chapter on transitional care in congenital heart disease.
Pregnancy, contraception and gynecological issues are
discussed in more detail in the chapter relating to this topic. Travel Advice and Precautions
It has been reported that despite similar cyanosis, patients Special precautions for laboratory testing
with Eisemenger syndrome show less exercise performance,
more ventilation-perfusion mismatch and a worse quality of For accurate measurement of hematological parameters,
life when compared to complex cyanotic CHD patients with special precautions are taken with blood drawn from patients
pulmonary stenosis who are protected from severe pulmonary with cyanotic CHD. The hematocrit level of their blood
vascular disease (due to decreased blood flow to the lungs samples should be calculated by an automated electronic
because of the pulmonary stenosis). The oxygen saturation particle counter because the microhematocrit centrifugation
at rest predicts exercise capacity and ventilatory efficiency in results in plasma trapping and falsely raised hematocrit.
these patients.51,52 Sodium fluoride should be added to the tube carrying
People with cyanotic CHD should avoid dehydration and the blood sample to avoid the false reading of marked
exercising in extremes of weather conditions. Competitive hypoglycemia due to increased in vitro glycolysis.4
sports should be avoided in cyanotic patients. Regular
aerobic exercise with slow warm up and slow cool down is CONCLUSION
encouraged.
Adults with cyanotic CHD have multisystem involvement
Work Restrictions with issues that need close follow-up and care by a
multidisciplinary team (Table 2). Fundamental preventive
Many people with CHD are only able to work for limited strategies, early detection and timely care can improve long-
work hours. In addition, the emotional and mental intensity term survival and quality of life in these special individuals.
involved in completion of the tasks and physical limitations
due to scoliosis or reduced muscle strength may hinder. Faith and knowledge lean largely upon each other in the
The physicians should be supportive in providing letters or practice of medicine.
documents to the employers that will allow these people to —Peter Mere Latham 779
http://vip.persianss.ir
10
Table 2
Care of the adult with cyanotic congenital heart disease: general considerations
Congenital Heart Disease in Adults
780
55
REFERENCES 19. Perloff JK. Cyanotic congenital heart disease the coronary
arterial circulation. Curr Cardiol Rev. 2012;8:1-5.
http://vip.persianss.ir
10
37. Lewis JG, Gardner JE. The relation of serum uric acid to 46. Siu SC, Sermer M, Harrison DA, Risk and predictors for
hemoglobin level in patients with cardiac and respiratory pregnancy-related complications in women with heart disease.
Congenital Heart Disease in Adults
782
Pregnancy, Contraception and
C hapter
http://vip.persianss.ir
10 BOX 1: Preconception clinical assessment in women BOX 2: Cardiac diagnostic tests in pregnancy
with congenital heart diseases Electrocardiogram
Congenital Heart Disease in Adults
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
There is a modest decrease in systolic blood pressure
Systolic blood pressure Mildly decreased
(10–15 mm Hg) and a more significant drop in diastolic blood
Diastolic blood pressure Decreased pressure (20–25 mm Hg) that occurs in the first trimester
Pulse rate Increased by 15 to 20% resulting in widened pulse pressure by mid-pregnancy. Blood
Cardiac output Increased by 30 to 50% pressure during pregnancy is affected by maternal age over 35
Systemic vascular resistance Decreased
years and parity.12
The systemic vascular resistance (SVR) decreases during
Pulmonary vascular resistance Decreased
the first two months of pregnancy due to hormonal influences
Plasma volume Increased by 40 to 50% (estrogen, prolactin and progesterone), along with a decrease
RBC mass Increased by 20 to 40% in pulmonary vascular resistance (PVR). These changes
Hemoglobin/hematocrit Decreased result in an associated increase in uterine and regional blood
flow.11,13 Regurgitant valve lesions are therefore well tolerated
during pregnancy, unless there is severe systemic ventricular
The maternal plasma volume progressively expands during dysfunction. The mean pulmonary artery pressures remain
pregnancy and rises by 40 to 50 percent of the pregestational similar to pre-gestational values.
volume by the 32nd week of gestation. A greater increase in Maternal position exerts a profound mechanical effect on
volume is noted in multigravidas (as compared to primigravidas) cardiovascular hemodynamics, particularly towards the end
and in twin pregnancies (as compared to a singleton of gestation, causing positional fluctuations in cardiac output
pregnancy).5,6 Distension of the atrial tissue may increase the by the 38th and 40th weeks. There may be compression of the
risk of atrial arrhythmias during pregnancy. Overall, the cardiac inferior vena cava by the gravid uterus in the supine position,
output increases by 30 to 50 percent and stroke volumes rises by which can decrease venous return, stroke volume and cardiac
18 to 25 percent. Since the uteroplacental blood flow is directly output.14 In the last trimester, approximately 8 percent of
dependant on the cardiac output, a decrease in cardiac output is women will experience light headedness and nausea. This
associated with intrauterine growth restriction (IUGR) and an ‘supine hypotensive syndrome’, can be relieved by placing
increased likelihood of preterm delivery.7 the patient in the lateral recumbent position.15 This is also the
The rise in red cell volume is around 20 to 40 percent of preferred position in late pregnancy, during labor and delivery.
the pre-gestational values, causing a relative reduction of the No changes in cardiac output are observed in this position. Of
maternal hemoglobin concentration, also known as dilutional note, the blood pressure taken in the supine position will be
anemia or physiological anemia of pregnancy.8 Most women higher than that taken in the left lateral position.10,16,17 The
may appear anemic with hemoglobin levels of 11 to 12 g/100 hemodynamic changes during pregnancy return to the baseline
ml and hematocrit levels as low as 33 to 38 percent during the values usually within 6 to 8 weeks postpartum.
second trimester.8,9 An increase in extravascular fluid is caused
by a rise in plasma aldosterone levels, which promotes sodium ANTEPARTUM ASSESSMENT
retention that leads to an increase in body water.6 Women often
encounter peripheral and generalized edema in late pregnancy. From the cardiovascular standpoint, pregnancy is usually
This is due to the additive effect of elevated venous pressure in well tolerated in the first trimester, since major hemodynamic
the lower extremities and the increase in extravascular fluid. changes do not occur until the second and third trimester
Pregnancy is a thrombogenic state as a consequence of of pregnancy. The most important change is an increase in
the changes in the coagulation cascade. This results from an cardiac output by 20 to 24 weeks, due to an increase in blood
increase in clotting factors and decreased fibrinolysis. There is volume and heart rate. These changes pose a burden on the
an additive effect of increased venous stasis. During pregnancy/ systemic ventricle and residual heart defects, which should be
postpartum period, women are at risk for developing deep identified and repaired before pregnancy, if possible.
venous thrombosis, especially when they are inactive or on Physicians and nurse specialists should be familiar with the
bed rest. Those with intracardiac shunts are at risk of having physiologic findings on cardiovascular examination during
transient ischemic attacks or stroke, due to paradoxical emboli. pregnancy. By the 12 to 20th week of gestation, there may be
The heart rate progressively rises by 10 to 20 bpm or 17 tachycardia with pulse rates 10 to 20 beats per minute above
percent over pregestational rates, with mean values ranging baseline, a widely split first heart sound due to early closure
from 78 to 89 beats per minute. Changes in body position of the mitral valve and a third heart sound. In addition, there
from supine to lateral may cause a decrease in heart rate.10 may be low intensity ejection systolic murmurs along the left
The cardiac output rises by 30 to 50 percent over nonpregnant sternal border due to a hyperdynamic circulation.18 In the last
levels, since it is the product of an increase in stroke volume trimester, a systolic murmur originating from the branches of 785
http://vip.persianss.ir
10 the internal thoracic (mammary) artery and a continuous bruit fetal defects may require a planned delivery at a tertiary care
originating in the veins of the breast may be heard.19 Women center, or in some cases, medical termination of pregnancy.
often have varicose veins and peripheral edema. Counseling should be offered to the parents of the offspring
Congenital Heart Disease in Adults
Among the abnormal heart sounds during pregnancy are a and the involvement of a clinical social worker helps the
fixed splitting of the second heart sound, a fourth heart sound, family deal with the challenges.24
a loud systolic murmur (over grade 3/6) or the presence of any
diastolic heart murmurs. DETERMINING THE MATERNAL AND FETAL RISK
Early on and when indicated in pregnancy, medications
need to be reviewed for their safety data, as well as for Pregnancies in women with CHD without potential risk
potential teratogenic effects and prescribed only if necessary. factors are likely to carry low maternal and fetal morbidity/
More current information on the medications and their effects mortality. Pregnancy carries the highest risk in women with
during pregnancy can be obtained from certain websites at no Eisenmenger syndrome with the postnatal maternal mortality
charge or subscription (www.drugs.com). as high as 50 percent. Another high-risk scenario is a woman
Electrocardiograms and transthoracic echocardiograms with Marfan syndrome and a dilated aortic root over 4 cm,
can be performed safely as and when indicated. Stress testing which can be at high risk for an aortic dissection. This may
should be avoided whenever possible during pregnancy. A occur due to the impact that hemodynamic and hormonal
submaximal treadmill stress test (70% of the maximum age changes of pregnancy have on the aneurysmal aorta.
predicted heart rate on Bruce protocol) is performed only if Pregnancy is therefore contraindicated in these women.
strongly indicated. Exposure to radiation should be minimized Risk factors for maternal morbidity include poor maternal
and avoided unless absolutely necessary. Abdominal shielding functional class, poorly controlled arrhythmias, heart failure,
should be provided when the procedure is necessary and the cyanosis, significant left heart obstruction and a history of
risk versus benefit ratio is in favor of performing the procedure. cerebral ischemia. The common maternal risk factors are
The risk of radiation exposure to the fetus should be discussed listed in Box 3. Maternal health status, especially cyanosis
with the patient. When possible, the procedures should be and exposure to teratogenic drugs are the major risk factors
postponed, until late second or third trimester of pregnancy. for fetal and neonatal complications. Box 4 addresses the
One such case could be a woman with critical aortic stenosis or major fetal risk factors.
severe mitral stenosis who may need emergent valvuloplasty, Siu et al described a risk index scoring system to predict
if she is in heart failure due to progressive volume load during the risk of adverse maternal events.25 In order to calculate
pregnancy. the score, the risk index awards one point each for poor
functional status (New York Heart Association [NYHA] > II),
Screening for Congenital Heart Diseases in the Offspring cyanosis (oxygen saturation < 90%), left ventricular systolic
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
• H istory of prior cardiac events such as arrhythmias, heart
Atrial septal defects (ASD), ventricular septal defects
failure, transient ischemic attack/stroke
• Prior arrhythmias such as symptomatic sustained (VSD) and patent ductus arteriosus (PDA) are common lesions
tachyarrhythmia or bradyarrhythmia requiring treatment with a left to right shunts.29,30 Women with unoperated or
• Poor functional class (New York Heart Association residual VSD or PDA are at high risk of developing infective
[NYHA] class > 2) endocarditis.31 Long-standing large shunts may predispose
• Cyanosis with low oxygen saturation of < 90% on room to pulmonary vascular disease and significant pulmonary
air hypertension. Eventually the rising right heart pressures may
• Significant valvular and outflow tract obstruction (aortic cause reversal of the shunt (right-to-left rather than left-to-
valve area < 1.5 cm2, mitral valve area < 2 cm2, or left
right shunt) leading to Eisenmenger physiology.
ventricular outflow tract peak gradient > 30 mm Hg)
Even after patch closure of an atrial septal defect, women
• Systemic ventricular ejection fraction < 40%
may have supraventricular arrhythmias during pregnancy.
The risk index score is the sum of the points (one point is
Postventriculotomy ventricular tachycardia or conduction
awarded for each risk factor listed above) that predicts the
percentage likelihood of adverse maternal events. Women block may occur following patch repair of a VSD. An early
with risk index of < 1, 1 and > 1, have a 5%, 27%, and 75% surgically ligated or divided PDA poses no additional hazard
likelihood of pregnancy-related complications (Adapted from to the mother or the fetus.
Siu et al)25.
Atrial Septal Defects
dysfunction, left heart obstruction and a history of cardiac In a study of pregnancies in women who have ASD and
events prior to pregnancy including arrhythmias, stroke, or no associated lesions, a higher risk of neonatal events was
pulmonary edema.25,26 A risk index score of 0 indicates an noted in women with unrepaired ASDs. The risk of cardiac
approximate risk of 5 percent, a risk index of 1 correlates with and obstetrical complications were comparable between
a 27 percent of adverse maternal events, whereas a woman the women with unrepaired and the repaired ASDs. Women
with a risk index greater than 1 has a 75 percent likelihood of with unrepaired ASDs had an increased incidence of pre-
adverse events (Box 5). eclampsia, small-for-gestational-age babies (less than the 10th
On the basis of these risk factors and the available data, percentile) and a higher fetal mortality (intrauterine death at
women can be stratified into low, intermediate, or high- or after 20 weeks of gestation). Cardiac arrhythmias, namely
risk categories. Unfortunately, most of the current data on nonsustained ventricular tachyarrhythmia and supraventricular
outcomes of pregnancy for individual defects are based arrhythmias (atrial fibrillation or supraventricular tachycardia)
on retrospective case series or case reports. Therefore occurred in 4.3 percent of the pregnancies, more often in older
decisions are often based on clinical experience.27,28 A women and in those with previous history of arrhythmias.
referral to a regional adult congenital heart disease (ACHD) One woman with an unrepaired ASD had a transient ischemic
clinic/tertiary care center is recommended for pregnant attack in the postpartum period, probably due to paradoxical
women who are at intermediate to high risk for maternal- embolism. Reduced exercise tolerance and mild heart failure
fetal complications. Included among the women identified were noted in around 3 percent women during pregnancy.32
as having a high risk score, are those with unoperated
or operated complex CHD, such as transposition of the Ventricular Septal Defects
great arteries postatrial switch repairs (Mustard/Senning
procedure) or univentricular hearts post-Fontan procedures. A recent study comparing outcomes of pregnancy in women
with unrepaired versus repaired VSDs showed a higher
CONGENITAL HEART DISEASES AND PREGNANCY incidence of pre-eclampsia (8.7%) in those with unrepaired
VSD, mostly occurring after 34 weeks of gestation. A higher
A brief overview of the potential maternal and fetal incidence of preterm labor was noted in women with repaired
management issues associated with simple and complex VSDs, probably related to a greater background risk with
CHD, most often encountered at a regional ACHD center, are relatively larger VSDs having undergone surgical repair. The
discussed below. mechanism of these observations is not clear. One woman with
an unrepaired VSD suffered Streptococcus viridans infective
Shunt Defects endocarditis involving a right heart valve in the postpartum
period, despite receiving antibiotics during an uncomplicated
Patent foramen ovale, although not always classified as a vaginal delivery. The incidence of recurrence of CHD was
CHD, is arguably the most common CHD with a right to 2 percent.33 Other studies have shown a lower incidence of 787
http://vip.persianss.ir
10 pre-eclampsia (1.8%) as reported in a literature review by The major maternal complications were hypertension-related
Drenthen et al.28 disorders noted in 15 percent of the women. Four pregnancies
were complicated by pre-eclampsia and two women had
Congenital Heart Disease in Adults
Patent Ductus Arteriosus eclamptic seizures. These observations are unusual, because
the incidence of hypertension-related disorders and eclampsia
Depending on the size of the ductus and degree of shunt, there were much higher than seen in the general population.
is an increased risk for developing pulmonary hypertension, Thromboembolic events occurred in nearly 4 percent pregnant
congestive heart failure and bacterial endocarditis/endarteritis. women with pulmonary stenosis. Cardiac problems were
The maternal morbidity and mortality in unrepaired PDA is palpitations/arrhythmias in nine women and deterioration
low. Women with a ligated or divided isolated PDA carry no in functional class in two women persisting for one year
risk in the presence of normal left ventricular function and postpartum. Fetal complications were premature deliveries in
normal pulmonary arterial pressures.34 17 percent, fetal mortality in 4.8 percent and occurrence of
CHD in offspring 3.7 percent.38
Atrioventricular Septal Defects Although, there is no clear explanation for the higher
incidence of non-cardiac complications among these women
In atrioventricular septal defects (AVSD), the architecture undergoing pregnancy, early detection and close attention to
of the fibrous skeleton of the heart is structurally different risk factors for hypertension-related disorders and premature
from other septal defects and therefore, the clinical outcomes, birth are advocated to improve maternal and fetal outcomes.
surgical repair, residua and sequelae differ significantly. Due
to these complexities, pregnancy is not always well tolerated Bicuspid Aortic Valve
in women with AVSD.
In a multicenter study with 29 women who had 62 Bicuspid aortic valve (BAV) is one of the most common
pregnancies, including 12 miscarriages (19%) and two CHDs.29,30 Pregnancy with mild to moderate stenosis is well
elective abortions, cardiovascular complications occurred tolerated. However, severe stenosis encroaches upon the
in almost 40 percent of the term pregnancies. There was circulatory reserve (valve area less than 1 cm2) and valve
deterioration in functional class (NYHA) seen in 23 percent replacement/repair should be advised before pregnancy.
and worsening of pre-existing atrioventricular (AV) valvular Women proceeding with severe aortic stenosis (AS) are at
regurgitation in 17 percent. Cardiac arrhythmias occurred in risk for developing heart failure (44%),36 angina, syncope
19 percent and symptomatic heart failure in 2 percent of the and sudden cardiac death during pregnancy. The aortic root
women. Mortality was high among the children (6.3%), since should be monitored in women by echocardiography during
12 percent had complex CHD. Among the three children who pregnancy for dilatation/dissection.
died, two children had left-sided hypoplasia.35 In a study with 39 women who had congenital aortic
stenosis (AS) and carried 49 pregnancies, Silversides et
Obstructive Outflow Tract Defects al report that although more than one-half had severe AS,
most of them were asymptomatic before pregnancy. Early
Pulmonary Stenosis cardiac complications, including pulmonary edema and atrial
arrhythmias, occurred in three pregnancies. One of those cases
Pulmonary stenosis (PS), the most common form of a right- was a woman with critical aortic stenosis who required urgent
sided obstruction, may occur as an isolated heart defect.29,30 percutaneous aortic valvuloplasty at 12 weeks’ gestation.
The clinical presentation depends upon the severity of the The severity of AS dictated cardiac complications (10%
obstruction and can vary from being asymptomatic with good occurred in severe AS, compared to none in mild or moderate
long-term outcomes as seen with mild stenosis, to the presence AS). Fetal complications included prematurity (8%), small
of right ventricular hypertrophy, right heart failure and sudden for gestational age (2%) and neonatal distress respiratory
cardiac death in uncorrected cases of severe pulmonary syndrome (6%).39
stenosis. Balloon valvuloplasty is therefore recommended In a follow-up study on late outcomes after pregnancy with
when the resting gradient across the right ventricular outflow congenital AS, Tzemos and Silversides et al reported that
tract is over 50 mm Hg or when the patient is symptomatic prior women with moderate or severe AS who were symptomatic
to conception. It need not be performed during pregnancy in during pregnancy were at higher likelihood of requiring
women who are asymptomatic or mildly symptomatic. Most cardiac interventions late after pregnancy. There were also at
women will tolerate a vaginal delivery.36,37 risk of experiencing a higher frequency of late cardiac events
Surprisingly, an excessive rate of noncardiac complications than those who had not been pregnant (31% vs. 0%).40
was reported in one multicenter study with 51 women with In another multicenter study, Yap et al followed-up
corrected pulmonary stenosis, who had 108 pregnancies, 53 successful pregnancies in 35 women (from a total of
788 including 21 (19%) miscarriages and 6 elective abortions. 58 pregnancies resulting in three miscarriages and two
abortions). The most serious cardiac complications (9.4%) changes in pregnancy cause some women to suffer aortic 56
were heart failure (3.8%) and atrial arrhythmia (5.7%). rupture and dissection during pregnancy or postpartum.
Interestingly, noncardiac complications were far more Women with CoA have been reported to have a higher risk
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
common with obstetric issues occurring in 22.6 percent and of hypertensive complications of pregnancy in many series.
perinatal complications in 24.5 percent. Hypertension-related The incidence of pre-existing hypertension complicating
disorders (including one case of eclampsia) were noted in pregnancy and pregnancy-induced hypertension are both
six pregnancies (11.3%). Fetal complications were mainly increased in this population.44,45 In a study by Krieger et al,
premature births in 7 (13.2%) and small for gestational age hypertension occurred in 24.1 percent of all women with CoA
births in 7 (13.2%). They concluded that pregnancy in women during their pregnancies, and 13.9 percent of those who were
with severe AS was associated with an increased incidence previously considered normotensive were diagnosed with
of heart failure, premature labor, and shorter duration of hypertensive disorders during pregnancy.45 Although the
pregnancy, with a higher likelihood of perinatal events in guidelines for the care of ACHD recommend vaginal delivery
women over the age of 30.41 in most cases, except in the setting of an obstetric indication
Preconception counseling is very important in women for cesarean delivery, this study noted that women with CoA
with AS. The risk of late cardiac outcomes after pregnancy have a higher rate of delivery by cesarean section and longer
should be considered in those with moderate to severe aortic hospitalizations, than seen in the general population.45
stenosis. Balloon valvuloplasty or aortic valve replacement Beauchesne et al reported 118 pregnancies in 50 women
(bioprosthetic) should be recommended before pregnancy. with CoA and found a 34 percent incidence of hypertensive
During gestation, in severely symptomatic women who are complications.46 Women with unoperated coarctation of aorta
unresponsive to medical management (mainly diuretics), often become hypertensive in the third trimester of pregnancy.
early delivery should be considered once fetal lung maturity They may develop paracoarctation aortic aneurysm/dissection
is achieved (usually around 36 weeks of gestation), so that and should have resection with end-to-end repair before
the mother can then undergo intervention or aortic valve conception. Unfortunately, risks persist in some women even
surgery. Those who cannot deliver the baby may require early after having the operation. These include hypertension (not
termination of pregnancy or relief of stenosis by percutaneous related to age at the time of repair), aortic root dissection and
balloon valvuloplasty or surgery. Although percutaneous rupture of berry aneurysms that occur even in normotensive
balloon valvuloplasty carries a risk of fetal radiation (partially patients. The residual aortic gradient was associated with an
reduced by abdominal shielding), it is preferred over surgery increased risk for hypertensive complications of pregnancy.46,47
for aortic valve replacement, since the later carries higher risk All patients should have adequate blood pressure control and
of maternal morbidity and fetal loss. aortic root monitoring. The goal is to maintain a systolic blood
High risk anesthesiologists should assist with hemodynamic pressure between 100 to 120 mm Hg and a diastolic blood
monitoring during labor and delivery in patients with moderate pressure between 60 to 80 mm Hg.
and severe AS. Vaginal delivery with an assisted second stage Hypertension in pregnancy has also been linked to adverse
of labor is the preferred mode of delivery, with cautious use fetal outcomes, including higher incidence of preterm
of adequate regional anesthesia in order to avoid a decrease delivery, low birth weight for gestational age and admissions
in systemic vascular resistance that may be poorly tolerated. to a neonatal intensive care unit.48
General anesthesia is preferred in women with severe aortic
stenosis undergoing a cesarean delivery.42 Cyanotic Congenital Heart Disease
http://vip.persianss.ir
10 may be associated with left ventricular dysfunction, severe in these studies, probably because of caution on the part of
pulmonary hypertension and severe pulmonary regurgitation obstetricians in these more vulnerable mothers and babies. The
with impaired right ventricular function.49 rate of antenatal complications was reported as significantly
Congenital Heart Disease in Adults
The postventriculotomy scar exacerbated by a mechano- higher in a study by Gelson et al.60 They noted a more frequent
electrical disturbance caused by severe pulmonary regurgita use of epidural anesthesia, shorter length of the second stage,
tion, can trigger monomorphic ventricular tachycardia.54 An with both spontaneous and assisted deliveries, in the women
echocardiogram should be performed during every trimester with repaired TOF. Women with moderate to severe pulmonary
or when indicated, to measure aortic root dilatation since regurgitation also had small-for-gestational-age offsprings.
dissection has been reported in individuals with markedly Preconception counseling is very important in this
enlarged aortic root.55,56 The occurrence of CHD in the population in order to review the circulation with particular
offspring is as high as 6 percent of livebirths. The 22q11 attention to severe right ventricular outflow tract obstruction,
deletion is associated with DiGeorge syndrome and tetralogy severe pulmonary regurgitation and right ventricular
of Fallot.49 dysfunction. Since pregnancy carries the risk of arrhythmias,
In a retrospective review of 40 deliveries in 25 patients right ventricular failure and endocarditis, an elective-induced
with repaired TOF, Kamiya et al reported that 17.5 percent delivery should be planned once fetal lung maturity is
pregnancies were complicated by cardiac events (mainly due attained. A plan for delivery should be agreed and documented
to decline in functional class and arrhythmias). The main by the team taking care of the patient. Close follow-up and
predictors of adverse outcomes were history of ablation and the management of heart failure and arrhythmias is important.
increased baseline cardiothoracic ratio on chest radiography. If right ventricular failure occurs, preterm delivery should
While left ventricular size and function did not change with be considered. Vaginal delivery with low-dose combined
pregnancy, the right ventricle was enlarged at 6 months after spinal-epidural analgesia and assisted second stage of labor
delivery and could potentially affect the long-term prognosis is recommended. When cesarean delivery is indicated for
of women with repaired TOF.57 obstetric reasons, a low-dose combined spinal with incremental
In another large retrospective international multicenter epidural anesthesia, or incremental spinal catheter anesthesia,
study of 157 pregnancies in 74 women with corrected are both suitable. General anesthesia is usually reserved for
TOF, Balci et al reported 123 completed pregnancies with emergency situations.61 Invasive hemodynamic monitoring is
associated maternal cardiac events in 8.1 percent and not recommended, since there is a higher risk of complications
obstetric complications in 58.9 percent. There were adverse and limited clinical benefits. Noninvasive hemodynamic
fetal outcomes in 33.9 percent. The mortality in the offspring monitoring with periodic blood pressure readings, continuous
was 6.4 percent. The most important predictors of adverse telemetry to check for arrhythmias and pulse oximetry for
maternal outcomes were the use of cardiac medications before oxygen saturations are recommended.
pregnancy, prior surgery for pulmonary valve replacement It is important to note that the radial pulse will not be
(PVR) and the occurrence of arrhythmias before pregnancy. palpable on the same side as the Blalock-Taussig shunt.
Previous history of PVR was associated with arrhythmias, and All women should receive prophylaxis against bacterial
in one pregnancy, there was pulmonary embolism along with endocarditis and deep venous thrombosis.
arrhythmias, while another pregnancy in the PVR group was
complicated by arrhythmias and heart failure.58 Dextro or d-Transposition of the Great Arteries
The use of cardiac medications before pregnancy was also
associated with birth of significantly small-for-gestational- In d-Transpostion of the great arteries (d-TGA), there
age babies. The reason for the association between adverse is ventriculoarterial discordance due to the transposed
maternal/fetal events and the use of cardiac medications pulmonary artery and the aorta.29 Most women with d-TGA
before pregnancy, may reflect a need based on less favorable have previously undergone an atrial switch repair (Mustard
baseline cardiac condition in terms of ventricular function and or Senning procedure) and their morphological right ventricle
history of arrhythmias. The use of cardiac medication before is the systemic ventricle that pumps into the aorta. Currently,
pregnancy was noted in 71 percent of women with PVR and more women with arterial switch repair (Jatene procedure)
right ventricular dysfunction, indicating late timing of PVR. are entering into their child-bearing years.
In these cases, the PVR was performed when long-standing
pulmonary regurgitation had already compromised the right
ventricular function, predisposing to arrhythmias post-PVR.58 Atrial Switch Repair
A possible relation between severe pulmonary regurgitation In a multicenter study, Canobbio et al reported that in women
and symptomatic right heart failure has been noted in other with atrial switch repair (Mustard or Senning procedure), there
series.59 were cardiac complications, primarily heart failure and atrial
The threshold for performing cesarean delivery for arrhythmias, most often in the third trimester, in 36 percent
790 obstetric/offspring reasons appears to be lower than usual of the pregnancies. There were two maternal deaths after
delivery. The fetal complications seen in 39 percent included a events occurred during or after any pregnancy. Two women 56
high rate of fetal wastage, low birth weight and prematurity.62 with dilated aortic roots did not have progressive enlargement
Similar risks have been shown by other studies.63-66 The in pregnancy or postpartum. No maternal mortality was
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
systemic (morphologic right) ventricle is likely to become reported in this study nor were there any significant adverse
further dilated with volume load of pregnancy. The success of fetal outcomes other than one small-for-gestational-age baby
pregnancy is related to function of the systemic right ventricle born to a mother who had multiple comorbidities.68
prior to pregnancy, as well as the degree of aortic and tricuspid
insufficiency.65 Congenitally Corrected Transposition
A more recent study by Metz et al prospectively followed of the Great Arteries
the right ventricular function through pregnancy and the
postpartum period.67 There was a fall in the systemic right In congenitally corrected transposition of the great arteries
ventricular function in 89 percent women during pregnancy (CCTGA) there is transposition of the great arteries
and although there was an improvement in the postpartum (ventriculoarterial discordance) and ventricular inversion (AV
period, the baseline function was not regained completely. discordance). Although the circulation is physiologically)
The degree of tricuspid (left AV valve) regurgitation also corrected, the morphologic right ventricle is the subaortic
progressed, but improved after delivery. A unique observation sytemic ventricle. Commonly associated defects are
was the high rate of atrial baffle obstruction that occurred in ventricular septal defect and pulmonary stenosis.29
36 percent women during pregnancy, as compared with only Women with unoperated defects may have worsening
5 percent reported in the all patients after an atrial switch cyanosis, risk of stroke because of microcytosis, paradoxical
procedure. In all women, the superior limb of the systemic emboli and systemic emboli (with severe right ventricular
venous atrial baffle was obstructed significantly (and was cardiomyopathy). Heart failure occurs due to systemic
probably unmasked by the increased venous return that ventricular dysfunction and severe tricuspid regurgitation
occurs during pregnancy). The baffle obstructions required in both unoperated and operated cases.69,70 In those with
intervention in the postpartum period. biventricular repair, the risk of heart failure depends upon
the pregestational biventricular function. Maternal functional
capacity and cyanosis are major risk factors for fetal wastage
Arterial Switch Repair (6–27%) and the occurrence of CHD in the offspring varies
As the women with arterial repair for d-TGA plan to have from 2 to 18 percent.70
pregnancies, the potential long-term residual and sequelae of Management issues during pregnancy are usually related
this surgery have to be taken into account. Limited data are to heart failure or atrial arrhythmias. Fluid retention is treated
available regarding pregnancy in this population. with gentle diuresis. Rate control in atrial arrhythmias may be
Despite pulmonary artery banding before surgery to train achieved by using beta blockers (propranolol). Direct-current
the left ventricle to take over as the systemic ventricle, left (DC) cardioversion is safe when there is hemodynamic
ventricular function may still deteriorate gradually after instability. Ideally women with history of arrhythmias should
arterial switch operation in patients with d-TGA and an intact consider radiofrequency ablation (RFA) prior to carrying a
ventricular septum. Right ventricular outflow obstruction pregnancy. Women with unimpaired systemic ventricular
(subpulmonic stenosis/infundibular stenosis) is commonly function who are tolerating the pregnancy well may carry it
noted and may require intervention in 10 percent of the cases. to term and have an elective induced vaginal delivery with
Coronary events may occur in 7 percent due to an abnormal assisted second stage of labor under epidural anesthesia.
coronary anatomy or coronary ostial fibrosis at the site of the Those who are markedly symptomatic may need to deliver
reimplanted coronaries, or due to kinking, torsion or extrinsic as soon as fetal lungs are mature. Hemodynamic monitoring
compressions that require immediate surgery. should be noninvasive with blood pressure checks, telemetry
Tobler et al retrospective studied the prevalence of adverse to check for arrhythmia and pulse oximetry instead of invasive
maternal cardiac events during pregnancy in nine women monitoring.71
with arterial repair, who had 17 pregnancies. There were
four miscarriages. Five women had clinically important Ebstein Anomaly
valve lesions and one had left ventricular dysfunction prior
to pregnancy. Cardiac complications occurred in two women; Women with unoperated Ebstein anomaly of the tricuspid
nonsustained ventricular tachycardia was noted in one valve may develop increased cyanosis because of the right-
woman with impaired left ventricular systolic function and to-left shunt through an interatrial shunt. Right heart failure
postpartum valve thrombosis occurred in another woman may develop from severe tricuspid regurgitation and right
with a mechanical mitral (systemic atrioventricular) valve. ventricular dysfunction. Supraventricular tachycardia may
Although the left ventricular function deteriorated during occur because of an accessory pathway associated with Wolff-
pregnancy in two women, no pulmonary edema or ischemic Parkinson-White (type B) syndrome.12 791
http://vip.persianss.ir
10 In women with operated Ebstein anomaly, the outcomes Eisenmenger Syndrome
during pregnancy depend on baseline functional NYHA class,
adequacy of tricuspid valve repair or replacement, arrhythmias Eisenmenger syndrome (ES) is characterized by irreversible
Congenital Heart Disease in Adults
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
vasodilators carries a risk of clinical deterioration despite Anticoagulation
theoretically improving the pulmonary hypertension, by
causing a fall in systemic vascular resistance, an increase in The biggest challenges in anticoagulation during pregnancy
right-to-left shunting, worsening hypoxemia, acidosis and are the mechanical prosthetic valves.88 In a study of 33 women
decreased coronary artery perfusion.83 with 82 pregnancies, the risk factors for valve thrombosis
An elective cesarean delivery is usually scheduled between were based on type (mechanical), position (mitral), number
30 and 34 weeks of pregnancy, when the fetus is viable and of prosthetic valves, arrhythmias, previous thrombosis
before the occurrence of maternal hemodynamic compromise. and adequacy of anticoagulation. All fetal complications,
General anesthesia should be avoided and low-dose sequential stillbirths, spontaneous and therapeutic abortions, occurred
combined spinal-epidural or incremental spinal anesthesia is in women taking warfarin (5 mg or higher). Low-molecular
recommended, since both allow slow titration with minimal weight heparin use was associated with intrauterine growth
effects on the peripheral circulation.61 Close monitoring is retardation in 22 percent of the offspring. No anticoagulation
carried into the postpartum, since there continues to be a very regimen conferred complete protection from thromboembolic
high incidence of maternal mortality. phenomena in pregnancy.89
The protocols for anticoagulation during pregnancy should
COMMON MANAGEMENT ISSUES IN PREGNANCY be individualized and based upon patient preference and risk
profile. Some prefer warfarin, except, in the first trimester and
Endocarditis Prophylaxis 2 weeks before delivery, during which period unfractionated
heparin or enoxaparin is used. Others advocate subcutaneous
The American College of Cardiology (ACC)/American Heart unfractionated heparin (UFH) or enoxaparin throughout
Association (AHA) guidelines in 2007 advocate intravenous pregnancy followed by a switch to intravenous heparin two
antibiotic prophylaxis, at the onset of labor, in women with days before elective delivery.90-94 For higher risk patients,
moderate to high risk CHD.84 This comprises all CHD except warfarin dose should be adjusted to keep International
for an isolated or repaired atrial septal defect (6 months Normalized Ratio (INR) 2.5 to 3.5 and they should receive
after closure), repaired ventricular septal defect with no an aspirin 81 mg oral daily when UFH or enoxaparin is given
residual shunt, surgically ligated patent ductus arteriosus and to maintain a trough anti-Xa levels more than or equal to 0.8
extracardiac, cardiac pacemakers and defibrillators. IU/ml and peak anti-Xa levels less than 1.5 IU/ml. The anti-
The standard dosage of antibiotics are ampicillin 2 gm Xa levels should be monitored every 2 weeks, since the body
intravenous (IV)/intramuscular (IM) and gentamicin 1.5 mg/ surface area and the drug volume of distribution are constantly
Kg initially and second dose of ampicillin 1 gm IV/IM or changing in pregnancy.
orally 6 hours later. Vancomycin (1 gm IV over 1–2 hours)
plus gentamicin are used if the patient is allergic to penicillin. Aortic Root in Pregnancy
Due to the low risk of bacteremia, the guidelines do not advocate
prophylaxis for an uncomplicated vaginal or cesarean delivery. Many CHDs are associated with structural abnormalities
Since it is not possible to predict obstetric complications, most of the great arterial walls that lead to dilatation of the aorta
centers prefer to administer antibiotics at time of the rupture and/or the pulmonary arteries.43 Progressive dilatation of the
of the membranes during a vaginal delivery, because of the aortic root can occur in women with a bicuspid aortic valve,
high morbidity or mortality associated with endocarditis. No coarctation of aorta, large ventricular septal defect, tetralogy
major toxicities have been reported with dosage for bacterial of Fallot/pulmonary atresia with ventricular septal defect and
endocarditis prophylaxis.85 Concerns about inappropriate in truncus arteriosus.
obstetrical use of antibiotics mainly apply to situations other The potential risk of forming an aneurysm or dissection
than for bacterial endocarditis prophylaxis.86 is the highest at the time of labor and delivery because of a
surge in the cardiac output. Due to estrogen withdrawal, the
Deep Venous Thrombosis risk may continue to be high in the postpartum period. An
elective cesarean delivery is recommended in women with a
All women are hypercoagulable during pregnancy and have an dilated aortic root that is progressively increasing in size. The
increased risk of deep venous thrombosis (DVT), pulmonary risk of rupture/dissection rises when the diameter reaches 5 to
embolism, paradoxical embolism and stroke depending upon 5.5 cm or if dilatation of the aortic root progresses at the rate
the associated underlying cardiac defects. These women of 1 cm or greater per year.95 Asymptomatic women should
should be educated about preventive measures such as regular consider undergoing prophylactic aortic root repair prior to
ambulation, adequate hydration and support stockings. conception, even though the surgical risk associated with 793
http://vip.persianss.ir
10 aortic root surgery averages around 2.5 percent.96 According be used for rate control in the second and third trimesters. Anti-
to the clinical practice guidelines for thoracic aortic disease, arrhythmic agents should be avoided during the first trimester,
operative repair is indicated in symptomatic patients with since there are limited data on the safety of their use in
Congenital Heart Disease in Adults
aortic diameter over 4.4 to 5 cm and/or growth greater than pregnancy. Women with effective antitachycardia pacemakers
0.5 cm per year, in ascending aortic aneurysms associated with or implantable defibrillators, who take medications to reduce
Marfan syndrome, bicuspid aortic valve or other genetically- the frequency of overdrive pacing or discharge, can stop
medicated disorders that are at high risk for dissection. The antiarrhythmics during the first trimester. The preferred and
aortic root should be assessed annually if the diameter ranges safe method for terminating hemodynamically compromising
from 3.5 to 4.4 cm and semiannually if it is 4.5 to 5.5 cm.97 atrial arrhythmias during pregnancy is by DC cardioversion.100
Prior to conception, women undergoing an intracardiac
surgery for another indication should be considered for a Bradyarrhythmias
concomitant aortic root repair, if the aortic root is over 4 cm.
It is recommended that preconception transthoracic Women with pacemakers for sick sinus syndrome or
echocardiographic assessment of the aortic root dimensions30 chronotropic incompetence should have the lower rate limit
be performed, along with serial echocardiograms to document of the pacemakers increased to match the physiological heart
changes in aortic dimensions at 20 to 24 weeks of pregnancy rate increase during pregnancy. In women with re-entrant
and monthly thereafter until 4 to 6 weeks postpartum. type of arrhythmia potentially induced by premature atrial
beats, the lower rate limit of the pacemaker may be elevated
Arrhythmias to overdrive suppression of premature beats and decrease the
frequency of tachycardia.100
The severity and frequency of arrhythmias increases with The obstetric team should be aware that high doses of
hemodynamic changes in pregnancy. The relation between magnesium when used for treating pre-eclampsia or eclampsia
symptoms and cardiac arrhythmias was studied in 110 can increase pacing thresholds and this may lead to pacemaker
consecutive pregnant patients without evidence of heart failure to capture. This is especially important when there is
disease referred for evaluation of palpitations, dizziness and impaired renal function.
syncope. Holter monitoring showed an increased incidence
of mostly atrial and ventricular premature complexes (VPCs) Heart Failure
during pregnancy with a substantial reduction in the incidence
in the postpartum period. Although the number of simple Women with moderate or severely reduced systemic
and multifocal VPCs was higher in symptomatic patients, ventricular function and/or NYHA functional class III and
there was no significant correlation between the incidence of IV are at high risk for maternal complications and should be
arrhythmias and symptoms. Only 10 percent of symptomatic advised against pregnancy. There is cumulative effect of all
documented episodes correlated with the presence of pregnancies, including miscarriages and abortions, on the
arrhythmias.98 systemic ventricular function.101
Women with CHD are at increased risk of presenting for the In case of mild to moderate systemic ventricular
first time with a symptomatic arrhythmia during pregnancy or dysfunction, heart failure medications including angiotensin-
if previously diagnosed, are at the risk of recurrence of their converting enzyme (ACE) inhibitors and aldosterone
arrhythmias.99 In women with complex CHD, uncontrolled antagonists such as spironolactone, should be prescribed for
maternal arrhythmias can cause hypotension and decreased a year before considering pregnancy, with reassessment of
cardiac output, leading to poor perfusion of the placenta systemic ventricular function prior to conception. Since these
and fetus with possible premature deliveries of small-for- two medication classes are listed as pregnancy risk category
gestational-age babies. D, they should be stopped once the woman is planning
After considering the risk/benefit ratio for the mother and pregnancy. Other heart failure medications such as diuretics,
the fetus, antiarrhythmic therapy should be restricted for certain beta blockers (especially propranolol) and digoxin may
use in management of intolerable symptoms or intractable be continued during second and third trimester of pregnancy.
arrhythmias that may be potentially harmful to the fetus. Acutely decompensated heart failure in pregnant women
Based on the data from observational reports, most available requires admission to the cardiac care unit with 100 percent
antiarrhythmic drugs are classified as in pregnancy risk oxygen, diuretics and vasopressor support as indicated.
category C. Concerns regarding fetal safety should be set aside, while
trying to stabilize the mother. The patient should lie in the
Tachyarrhythmias left lateral position to improve her cardiac output. Invasive
monitoring is rarely indicated and should be avoided as far as
Adenosine may be used safely to diagnose or terminate a possible. Noninvasive methods of monitoring are preferred.
794 supraventricular tachycardia. Beta blockers and digoxin may Once stabilized, a woman in her third trimester, should be
considered for an induced delivery as soon as fetal lung may be adequate for anticoagulation in most cases, one may 56
maturity is achieved. require a higher dose of 2.5 to 3.0 for mechanical prosthetic
valve. Careful monitoring is required, since the volume
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
Common Cardiac Medications in Pregnancy of distribution of the drug is constantly changing during
pregnancy. Since fetal adverse effects are dose-related, women
Since none of the cardiac medications are absolutely safe for are advised to avoid dietary/supplemental intake of vitamin K,
the fetus during pregnancy, their use should be limited and so that daily dose of 5 mg oral or less may be required for
considered carefully only after reviewing the indications, adequate anticoagulation.91 It should be discontinued 2 weeks
safety data and pregnancy risk category classification before an elective delivery and replaced by unfractionated
(Table 2). Nursing mothers are advised to avoid feeding their heparin.
infants when the expected plasma concentration of the drugs
is the highest, even if no major clinical effects on infants have Side Effects
been reported for that particular medication.102
Some of the more commonly prescribed cardiac ‘Warfarin embryopathy’ is characterized by nasal hypoplasia
medications are discussed in this chapter. More up-to- and chondrodysplasia punctata that can occur in 6.4 percent
date information on cardiac medications in pregnancy live births.91 There is a potential effect on childhood growth
can be obtained from the US. Department of Health and and development.103 In addition, there is an increased risk of
Human Services, Office on Women’s Health (http://www. fetal hemorrhage and wastage.
womenshealth.gov/publications/our-publications/fact-sheet/
pregnancy-medicines.pdf) and from another website: www. Contraindications
drugs.com.
Warfarin should be avoided in the first trimester and its use
Warfarin should be restricted for anticoagulating mechanical valves in
second and third trimesters. An informed consent should be
Warfarin is classified as pregnancy category X. It inhibits obtained from the patient before prescribing it.
vitamin K-dependent coagulation factors, proteins C and S.
Low-molecular Weight Heparin
Standard Dosage
Enoxaparin is classified as pregnancy category B and is a
Dose is adjusted for the lowest INR required for adequate subcutaneously administered anticoagulant. It has a lower risk
anticoagulation for an indication. While a dose of 2 to 2.5 of osteoporosis than unfractionated heparin.104,105
Table 2
Classification of medications in pregnancy
Pregnancy Definition of the category Some commonly used medications in this category
category
A Controlled human studies showed no fetal risk Folic acid
B Controlled human studies have not shown fetal risk despite Amoxicillin
adverse findings in animal studies
or
Inadequate data from human studies, but animal studies
showed no fetal risk.
C Inadequate data in human and animal studies. More likely Most cardiac medications including low dose aspirin,
to have beneficial effects when used cautiously furosemide, digoxin, most beta blockers (except
atenolol), nitrates, hydralazine, adenosine, calcium
channel blockers and adenosine
D Data from human studies or subsequent use in humans Atenolol
demonstrates fetal risk Angiotensin-converting-enzyme (ACE) inhibitors
Drug may be rarely acceptable if needed in a life-
threatening situation or serious disease for which safer
drugs cannot be used
X Contraindicated in pregnancy Warfarin
Human and animal studies data show a very high risk of
adverse effects to the fetus 795
Based on the FDA system of classification: www.fda.gov
http://vip.persianss.ir
10 Standard Dosage for stroke prevention and as conjunctive therapy in high risk
mechanical valves. Its use should be stopped 2 weeks before
The dose is adjusted according to weight, creatinine clearance delivery to avoid bleeding, prolonged gestation/labor and
Congenital Heart Disease in Adults
and depending upon the indication. It is usually injected premature closure of fetal ductus arteriosus.
subcutaneously every 12 hours and held for at least 8 hours
(ideally for 24 hours) before an invasive procedure. In order Standard Dosage
to ensure adequate anticoagulation, the antifactor Xa levels
should be checked biweekly, 4 to 6 hour after an injection Low dose aspirin, 75 to 162 mg oral daily.
and maintained between 1.0 to 1.2 U/ml.89,91
Main Side Effects
Side Effects
Bleeding, low birth weight.
Bleeding and hematomas.
Contraindications
Contraindications
Allergic rhinitis/nasal polyps, salicylate hypersensitivity.
Bleeding, heparin-induced thrombocytopenia (HIT), uncon-
trolled hypertension. Avoid intramuscular injections and use Diuretics
in labor/delivery, since hematoma and bleeding are major
complications.106 Loop diuretics such as furosemide are in pregnancy category
C and are used to decrease fluid retention by increasing
Unfractionated Heparin urinary sodium excretion. They provide rapid symptomatic
relief in heart failure.
Unfractionated heparin is in pregnancy class C. It mediates
antithrombotic properties through an interaction with Standard Dose
antithrombin III and does not cross the placenta.
The initial dose is 20 mg oral daily, which is titrated to
Standard Dosage increase urine output and decrease weight by 0.5 to 1 kg daily.
Excessive diuresis should be avoided, since low cardiac output
Subcutaneously injected with an average dose of 5,000 decreases uterine perfusion and leads to fetal hypoperfusion.
to 10,000 U every 8 to 12 hours adjusted to body weight, Rare teratogenicity effects are oligohydramnios, intrauterine
or may be given as continuous intravenous infusion that growth restriction, hypospadias, and neonatal death from
is titrated to achieve an activated partial thromboplastin renal failure.
level (APTT), which is 1.5 to 2.5 times the normal value.91
It should be stopped 2 hours before delivery (vaginal or Main Side Effects
cesarean) and resumed 4 hours after, if it there are no contra
indications. Hypotension, electrolyte depletion (hypokalemia) and
azotemia. Serum electrolytes and creatinine should be
Contraindications monitored regularly. Potassium should be replenished to
maintain serum potassium levels between 4 and 5 meq/L.
Thrombocytopenia, hemorrhage (except in disseminated
intravascular coagulation). Beta Blockers
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
aorta, even though the evidence of benefit is limited in those outflow tract lesions, WPW syndrome, sinus node dysfunction,
without Marfan syndrome. conduction disease, and in the presence of renal impairment.
Since beta blockers cross the placenta, fetal bradycardia
and hypoglycemia may occur. Although teratogenicity is low, Hydralazine
preterm labor, prematurity and intrauterine grown retardation
may occur due to reduce uterine blood flow. Low birth- Hydralazine is in pregnancy class C and acts by direct
weight babies have been reported, especially with the use of arteriolar vasodilatation and may be used for management of
atenolol.107 heart failure and hypertension.
Main Side Effects Adenosine belongs to pregnancy class C and is the most
rapidly acting endogenous modulator of smooth muscle tone
Digoxin toxicity usually occurs in those with renal impairment that is often used to treat supraventricular tachycardia. No
and abnormal serum potassium levels. fetal adverse effects have been reported. 797
http://vip.persianss.ir
10 Standard Dose They have not been extensively studied for other indications
or in the first and second trimesters. Short-term use may be
A rapidly administered intravenous injection of 6 mg followed indicated for heart rate control in late pregnancy.
Congenital Heart Disease in Adults
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
fetal risk. This procedure can be cautiously performed during
the late second or third trimesters, with maternal abdominal Surgical Procedures
shielding to minimize fetal radiation exposure. All nonobstetric surgical procedures, other than emergency
operations, are best avoided during pregnancy.
Mode of Delivery
Cardiopulmonary Resuscitation
Unfortunately, cardiac arrest occurs in 1:30,000 pregnancies. The preferred mode of delivery is vaginal, with a facilitated
Women with CHD have a higher risk of sudden death from second stage of labor.
postventriculotomy scar causing ventricular tachycardia, or An elective induced delivery is preferred in women with
from severe cardiomyopathy or aortic dissection. Other causes complex CHD or high risk factors, usually after 37 to 38
include amniotic fluid embolism, eclampsia, drug toxicity, weeks when fetal lung maturity is achieved. Nearly all women
massive pulmonary embolism and hemorrhage. with CHD should deliver at a center with high risk obstetrics,
Cardiopulmonary resuscitation should be performed neonatology, pediatric cardiology and adult CHD specialists.
according to the standard ACLS algorithms. The pregnant All patients need hemodynamic noninvasive monitoring
woman should be moved to the left lateral decubitus position of blood pressure, heart rate, pulse oximetry. Telemetry is
to relieve inferior vena caval compression, improve venous indicated if there is a likelihood of developing arrhythmias.
return, and increase her cardiac output. The chest compressions Cesarean delivery is mainly performed for obstetric
are higher on the sternum to adjust for the elevated diaphragm indications, or in women on anticoagulation therapy with
caused by the gravid uterus. Emergency hysterotomy should warfarin, in order to avoid the potential risk of fetal intracranial
be performed within 4 to 5 minutes of cardiac arrest if the hemorrhage, because of fetal head compression in the birth
fetus is older than 25 weeks gestation, since delivering the canal during contractions.
fetus may improve venous return and maternal-fetal survival. Relative indications for a cesarean delivery include a
Maternal resuscitation is the key to fetus resuscitation and dilated aortic root (over 4 cm), severe valvular stenosis, 799
http://vip.persianss.ir
10 severe left ventricular outflow tract obstruction and severe Adult survival and advances in pregnancy risk stratification
pulmonary hypertension. of women with moderate to complex CHD have opened up
In the United States, there have been concerns about the door to procreation like no other generation living with
Congenital Heart Disease in Adults
the rising incidence of cesarean deliveries from 5.5 percent CHD. However, by eliminating the prohibition of pregnancy
in 1970 to 29.1 percent in 2004.111,112 There are significant for all, but a select few women with the most significant forms
associated risks including increased blood loss, delayed cardio/pulmonary disease, equal emphasis should be placed
ambulation and prolonged recovery. In addition, there is a on the importance of ‘planning’ a pregnancy, rather than
potential risk of scar rupture during labor and delivery with confronting an unplanned high risk pregnancy. Regrettably,
future pregnancies. After adjusting for possible confounding unplanned pregnancies are still the reality for almost half of
factors, the postpartum mortality is 3.6 times higher after all pregnancies,1 signifying a mismatch in either contraceptive
a cesarean delivery than a vaginal delivery, mainly due to counseling/access and/or contraceptive compliance. Kovacs
complications associated with anesthesia, puerperal infection and colleagues found that only 51 percent of women with
and venous thromboembolism.113 CHD recalled receiving information about birth control from
their health care provider.2 This reality makes effective,
Postpartum Care accessible, easy and safe contraception a mandate for this
complex population and ‘prepregnancy’ counseling is the
Women should be advised to resume contraception after responsibility of all ACHD providers.
delivery. They are often most receptive to procedures such Contraceptive options available today, provide women with
as permanent sterilization, if a future pregnancy is contra- CHD with many alternatives to prevent or postpone pregnancy.
indicated. Supportive care and education are usually well For women with complex congenital heart disease, they confront
received by the mothers. the highest risks with pregnancy, and therefore, a planned
pregnancy should always be approached as collaboration
DIET AND EXERCISE between the procreating couple, the fetus and the ACHD/high
risk obstetric team (comprising the cardiologist and nurse
A well-balanced diet with adequate fluid (preferably water) specialists in ACHD, a high risk obstetrician/perinatologist).
intake and minimized use of artificial sugar sweeteners is Part of that collaborative process usually entails a period of
advised in all women. Caffeine, alcohol intake and smoking time in which contraception is a necessity. The three biggest
are to be avoided during pregnancy. considerations in choosing optimal contraception are:
Prenatal vitamins should be started, while planning a a. The woman’s risk of thrombosis
pregnancy and continued while nursing or 6 months postpartum b. Contraceptive ease and efficacy
to replenish the iron and vitamin stores. Daily folic acid intake c. The degree of side effects. Choosing the lowest risk and
of over 400 micrograms reduces the incidence of neural tube most effective contraception can be a challenge for women
defects.4 Athough the daily intake of calcium should be over with the highest complexity of CHD.
1,500 mg (dietary and supplemental), no more than 600 mg The heterogeneity of congenital heart disease makes risk
should be taken at a time, to allow adequate absorption. stratification challenging. Some women have simple cardiac
Regular isotonic exercises and aerobic activity such as defects, which have little to no impact on their contraceptive
walking and swimming help with cardiovascular conditioning. and pregnancy decisions. However, for those women with
Jogging should be avoided during pregnancy. moderate to complex congenital heart disease, choosing a
safe contraceptive requires careful consideration of what their
CONCLUSIONs actual pregnancy risk is (moderate, high or prohibitive) and
what risks and benefits come with the preferred contraceptive
As more women with complex congenital heart defects are option. For example, women with a prohibitively high risk for
entering into their reproductive years, careful risk assessment pregnancy (Eisenmenger), the contraceptive option with the
and preconception counseling are becoming even more lowest possible failure rate (such as sterilization, intrauterine
important. Close follow-up with the perinatologists and devices [IUD], or contraceptive implants) might be
collaboration with a multidisciplinary team are essential for considered. On the other hand, a woman with complex CHD
favorable maternal and fetal outcomes. (such as double outlet right ventricle/Rastelli or transposition
of the great arteries/Mustard) may have a low risk for
ONTRACEPTIVE OPTIONS FOR WOMEN WITH
C thrombogenesis, but could confront dysfunctional menstrual
CONGENITAL HEART Diseases By Pamela bleeding or polycystic ovarian syndrome. The potential benefits
Miner, RN, MN, NP of a combined hormonal contraceptive such as a drospirenone
containing combined oral contraceptive (Yaz, Yasmin) might
Most children growing up with congenital heart disease in the be considered for both contraception and hormonal advantage.
800 21st century will live long enough to confront family planning. As this demonstrates, the decisions regarding contraception
can be more complicated than simply pregnancy prevention
Box 6: Contraindications for combined hormonal 56
and deserve comprehensive individualized evaluation and contraceptive use
treatment. Complicating matters is the paucity of published
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
General
data about contraceptive safety in women with CHD, since
Previous thromboembolic event or stroke
so much of our clinical decision making is based on data Inherited thrombophilia
regarding women with acquired cardiovascular disease and Smoking
perhaps more so by expert consensus. Even with the data Liver disease
published on contraceptive safety in women with other forms Pregnancy
of heart disease, the World Health Organization (WHO) and History of an estrogen-dependant tumor
the Centers for Disease Control, both emphasize the need Migraine headaches with aura
to take individual clinical circumstances into consideration Obesity
rather than holding firmly to published clinical guidelines.3 Age over 35
Cardiovascular
Hypertension
Contraceptive Options Coronary artery disease
Cerebrovascular disease
1. Combined hormonal contraceptives. Complicated valvular disease
2. Progestin-only contraceptives. Older-style mechanical valves (even on Coumadin)
3. Barrier methods/emergency contraception. Pulmonary hypertension
4. Intrauterine devices. Dilated cardiomyopathy with LVEF < 30%
5. Sterilization. Cyanotic congenital heart disease
6. Rhythm method/abstinence/abortion. Right-to-left shunting
History of Fontan procedures—highest risk with classic
Fontan (right atrium to pulmonary artery)/ or with a markedly
Combined Hormonal Contraceptives dilated right atrium.
Combined hormonal contraceptives contain both estrogen
and progestin and are highly effective at preventing
pregnancy (99.4%), when used correctly. They also have non- disease data. Thorne8 developed guidelines for contraceptive
contraceptive benefits, including reductions of menorrhagia, use in women with heart disease, including CHD. Their
dysmenorrhea, acne, hirsutism and ovarian cancers. The group categorized the highest risk groups from a thrombotic
evolution of these oral combined hormonal contraceptives standpoint to be those with older-style mechanical valves
in recent years has resulted in lower estrogen levels (20 to (even on Coumadin), pulmonary hypertension, and dilated
35 mcg) and new generations of progestin aimed at reducing cardiomyopathy with left ventricular ejection fraction (LVEF)
symptoms of menstrual syndromes. These changes have less than 30 percent. For these, the use of combined hormonal
resulted in fewer side effects and a reduction in thrombotic contraceptives was considered contraindicated. In addition,
complications.4,5 However, lower hormone levels in these patients with cyanosis (or right-to-left shunting) or Fontan
combined hormonal pills have resulted in higher susceptibility procedures were also considered to be at high risk for clot (or
to contraceptive failure if a single dose is missed in the first or at highest risk for complications related to clot) and cautioned
third week of hormones or the hormone free interval exceeds against the use of combined hormonal contraceptives. The
7 days, making back-up contraception a necessity, when these ACC/AHA guidelines for management of adults with CHD10
low estrogen oral preparations are used.6 shared some of the above concerns related to the highest risk
According to the WHO,7 the contraindications for using group, also warned against the use of estrogen containing
combined hormonal contraceptives include (Box 6): previous contraceptives in Fontan patients, pointing out that the highest
thromboembolic event or stroke or an inherited thrombophilia, risk Fontan patients appear to be those with older version, right
coronary artery disease or cerebrovascular disease, atrium to pulmonary artery (RA-PA), Fontans or massively
complicated valvular disease, women over age 35 who smoke, dilated right atriums. According to Thorne,8 treating the
liver disease, pregnancy, or a history of an estrogen dependent thrombotic risk in these patients with anticoagulation did not
tumor. In addition, special consideration of the thrombotic change the precautions against the use of combined hormonal
risks of combined oral contraceptives should be individually contraceptives. However, there are ACHD specialists who
assessed in the setting of hypertension, migraine headaches would consider using low estrogen oral contraceptives in
with aura, or in obese women over age 35. In women with women with newer version Fontans, total cavopulmonary
congenital heart disease, risk stratification is more challenging connection (TCPC), and no sustained atrial arrhythmias, or
due to lack of data regarding overall thrombogenicity and those who are consistently protected with anticoagulation.
ultimately rests on experiential inferences from those managing The risk of estrogen-provoked thrombus in women who are
adults with CHD8,9 and associations linked to acquired heart adequately anticoagulated is not known, so practice standards 801
http://vip.persianss.ir
10 in this regard are left to the treating physician. This is where systemic side effects of the other formulations of progestin
the experiential line is drawn, allowing for different practice (fluid retention, osteoporosis, etc.).
standards that each may hold merit, but make generalized
Congenital Heart Disease in Adults
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
have passed since intercourse. of a therapeutic (surgical) abortion should be included in all
contraceptive counseling, so that the woman understands the
Sterilization potential risk of anesthesia, blood loss, infection, damage to
the uterus or cervix and psychological injury imposed by a
Sterilization provides for the most efficacious and permanent surgical abortion, thereby emphasizing the importance of
form of contraception. Options include vasectomy, surgical ‘preconception’ action to avoid pregnancy.
tubal ligation and intratubal occlusion (known as Essure in
the United States). It is reasonable to recommend this form of Risk Stratification for Contraceptive Use
contraception to women who would confront a prohibitively
high risk with pregnancy, such as women with pulmonary Risk stratification can be divided into two main considerations,
hypertension (Eisenmenger syndrome). Laparoscopic the risk of thrombosis and the risk of maternal/fetal morbidity/
surgical tubal ligation presents a small perioperative risk, mortality with pregnancy (Table 3). Often, those at highest
particularly to women with pulmonary hypertension. clot risk are also those in whom pregnancy would be the
A cardiac anesthesiologist should be present during the most hazardous. The majority if women with CHD are at low
procedure in high-risk women. Intratubal occlusion (Essure) thrombotic risk. This includes those with unoperated valve
is a less risky option for permanent contraception and can disease, small VSD, postoperative coarctation with controlled
be performed using local anesthesia. A coil-like device is blood pressure, postoperative valve repair or bioprosthetic
embedded in the fallopian tubes via a transvaginal procedure valve replacements, tissue valved pulmonary artery conduits,
and causes irritation and scarring in the surrounding tubes. transvenous pacemakers without right-to-left shunts, atrial and
Complete tubal occlusion needs to be confirmed with imaging arterial switch repairs, Marfan syndrome and postoperative
studies 3 months postcoil occlusion, so intermediate forms shunt repairs in the absence of pulmonary hypertension. Those
of contraception need to be used in those first 3 months. at moderate thrombotic risk include women with a known
Vasectomy is a reasonable option and avoids any potential thrombotic potential protected with antiplatelet therapy or
risk confronted by the woman with CHD. One could argue anticoagulation as indicated. This includes patients with
that the male partner may outlive the female partner with mechanical valve prostheses, total cavopulmonary Fontan
CHD and as such, may desire future procreation options, repairs, sustained atrial arrhythmias, unrepaired atrial septal
but in this instance, vasectomy can be reversed. Therefore, defect, or dilated cardiomyopathy with class I-II symptoms.
sterilization using vasectomy should not be easily dismissed The highest thrombotic risk group includes those women
from consideration. with CHD whose potential for clot cannot be effectively
prevented, or in whom the consequences of a clot presents
Rhythm Method/Abstinence/Abortion significant morbidity or mortality. This includes women
with pulmonary hypertension (Eisenmenger syndrome),
Rhythm method/abstinence/abortion are the least desirable cyanosis, atriopulmonary Fontan repairs, NYHA class III-
options for ‘family planning’. In the first half of the 20th IV heart failure with dilated cardiomyopathy, uncontrolled
century, prior to the era of birth control pills, the rhythm hypertension, inherited thrombophilia or documented past
method, withdrawal or abstinence were a woman’s only thrombotic tendency, obesity, or women over 35 years of age
choices for preventing pregnancy. The rhythm method is only who smoke.
marginally effective if a woman has very regular menstrual Women in the low thrombotic risk group are candidates
cycles and can precisely predict ovulation. Relying on this type for any form of contraception, including combined hormonal
of modification of one’s sexual relationship is unrealistic, as is contraceptives. Consideration must be given to those women
abstinence. Contraception is available to provide women with whose thrombotic risk may be low, but their pregnancy risks
choices that prevent pregnancy and provide more freedom in are high (such as severe aortic stenosis) and therefore, more
their sexual relationships. Fear and misinformation are often definitive contraception might be considered, such as an
the reason why a woman with CHD avoids entering into a IUD. For those with moderate thrombotic risk, nonestrogen
sexual relationship and this reflects a failure by the health care options for contraception should be considered first, but
provider to provide comprehensive contraceptive counseling. with individualized consideration towards modification of
This is both unfair to the woman and perhaps equally as thrombotic risk, one could consider a low estrogen containing
unfortunate as an unplanned pregnancy. Providers owe their combined hormonal contraceptive. This may be indicated if
patients accurate, understandable and accessible information a woman confronts considerable menstrual symptoms such
regarding their options for birth control. Abortion is not as heavy bleeding or polycystic ovaries. Clearly those at
803
http://vip.persianss.ir
10 Table 3
Risk stratification for contraceptive use
Congenital Heart Disease in Adults
the highest thrombotic risk are not candidates for combined education regarding contraception. Young female patients
hormonal contraceptives and should be guided to progestin should be referred to such a specialist if available, if only
only options, IUD, sterilization or combined barrier methods, to begin the conversation and guide future questions when
depending on their pregnancy risks and future procreation appropriate to their level of interest or evolving sexuality.
potential. When contraceptive choices are considered ‘contraindicated’
for certain patients, alternatives must be provided. As outlined
Contraceptive Counseling in this review, multiple options are available to young women
today, who desire sexual activity without the risk of pregnancy.
Contraceptive counseling is often the most difficult subject to Clearly additional investigation is necessary to outline
address for pediatric cardiologists, although the best time to the contraceptive risks confronted by women with complex
begin addressing this in young women with CHD is when they CHD.
are entering puberty. These discussions need to be reassessed
over time, accounting for all non-cardiac risk factors for YNECOLOGICAL ISSUES IN WOMEN WITH CHD By
G
thrombosis and any changes in maternal cardiac status.14 The Mary M Canobbio, RN, MN, FAAN
only way contraceptive counseling can be deemed a “failure”
is when it never takes place. One study found that 43 percent Medical and surgical advancements have allowed most females
of women with CHD had not been counseled regarding with CHD to survive into and beyond their reproductive
contraception, and 48 percent had not been informed about years. As a result, gynecological and reproductive issues
pregnancy related risks by their treating physician.15 Many have emerged as one of the most common noncardiac health
large ACHD centers have skilled nurse specialists who are care issues, cardiologist and other health care providers must
804 experienced in providing this level of comprehensive patient address as part of their clinical management.
MENSTRUATION uncorrected CHD. The use of anticoagulation also appears to 56
increase the risk of metrorrhagia or menorrhagia, although no
Menarche significant causal relationship has been reported. In the general
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
population, the primary causes include systemic illness (e.g.
Menarche occurs in the normal female population at a mean hypothyroidism) and intrauterine lesions (e.g. myomas) or
age of 12.3 years. For females with acyanotic congenital heart endometriosis. Chronic metrorrhagia and menorrhagia can
disease, menarche occurs a little later at 13 years and for result in iron-deficient anemia. For females with cyanotic
females with cyanotic CHD, it occurs at the average age of CHD, who are usually erythrocytotic as result of an adaptive
13.9 years.1 While the menstrual patterns in acyanotic females response to systemic arterial hypoxemia, hematocrit must be
with CHD are similar to the general population, females carefully monitored if oral iron replacement is required. This is
with cyanotic CHD often will have menstrual irregularities because an increase in circulation erythropoietin predisposes
including shorter or longer cycle lengths, a greater frequency to a rapid and excessive rise in hematocrit.5
of menstrual irregularities, breakthrough bleeding, and/or Metrorrhagia can be managed in the short-term with high-
missed periods including amenorrhea. dose progestins or dilatation and curettage. For prolonged
Limited data is available on the postoperative menstrual menstrual suppression, Depo-Provera or the progestin-
patterns in women with CHD. An early study reported that secreting intrauterine device may be considered. For women
Fontan operation performed before the age of 10 years was in whom pregnancy is not desired or when the risks are
associated with menarche at the same age as the normal female prohibitive, endometrial ablation or hysterectoscopy may be
population, while Fontan operation performed after menarche considered.
was associated with resumption of normal menstrual patterns Regardless of cause, females with DUB require a thorough
within 6 months of surgery.2 gynecologic evaluation, which includes a detailed menstrual
A subset of patients who remained cyanotic beyond history supplemented by a pelvic examination and pap
menarche reported dysfunctional bleeding evidenced by smear. Medical treatment of DUB includes a combination
complaints of oligomenorrhea, metrorrhagia and amenorrhea oral contraceptive pills, however, the use of estrogen is
suggesting a possible relationship with the duration of contraindicated in women at risk for thromboembolism.
cyanosis after menarche, although the exact cause remains to Progesterone alone can be used to stabilize an immature
be elucidated.2 endometrium and is usually successful in the treatment of
women with anovulatory dysfunctional uterine bleeding.
Dysfunctional Uterine Bleeding The concern for anovulatory patients is that if left untreated,
chronic unopposed estrogen production can result in
Dysfunctional uterine bleeding (DUB) is defined as abnormal continuous endometrial stimulation and hyperplasia that
uterine bleeding in the absence of organic disease and is may be accompanied by a three-fold increase in the risk of
the most common cause of abnormal vaginal bleeding in endometrial cancer.6,7 Additional therapies that have proven
women of child-bearing age. It is a diagnosis of exclusion to be effective in reduction of DUB include the use of anti-
and approximately 90 percent of dysfunctional uterine fibrinolytic tranexamic acid, nonsteroidal anti-inflammatory
bleeding cases result from anovulation while 10 percent of drugs (NSAID’s).7-9
cases occur with ovulatory cycles.3 Dysfunctional bleeding is
characterized by a variety of menstrual complaints including MEDICAL TERMINATION OF PREGNANCY
irregular noncyclic bleeding, heavy bleeding (metrorrhagia,
oligomenorrhea or amenorrhea). In cases of unplanned pregnancy, in women with CHD who
In the general population, amenorrhea occurs in 0.1 percent are at high risk for maternal-fetal complications, medical
to 2.5 percent of the women as primary or secondary cause. termination of pregnancy is often recommended. The decision
The occurrence of secondary amenorrhea is higher in CHD to medically terminate a pregnancy must be a collaborative one
(10.3%), while only 0.7 to 3.0 percent of the women in the involving not only the patient, her spouse or partner, family,
general population report this menstrual cycle disturbance.4 obstetric/gynecology service, ACHD specialist, and clinical
Causes of amenorrhea are similar to general population and social worker to discuss the risks associated with pregnancy,
include hypothalamic dysfunction, endocrine disorders and as well as ensure that the choice is made with consideration to
uterine disease. Patients cyanotic prior to menarche appear the patient’s personal beliefs.
to be at greater risk of developing secondary amenorrhea. Once a decision to terminate a pregnancy has been made, it
Oligomenorrhea also appears to be common in women is important to act swiftly, because the choice of procedure is
with CHD and the number of surgical interventions prior determined by the stage of pregnancy. An ultrasound should be
to menarche may be a potential predictor, even though the performed if there is discrepancy between dates and uterine size.
comparative data of the general population is lacking. During the first trimester termination of pregnancy (first
Metrorrhagia has been mainly reported by patients with 12 weeks of gestation), the methods are either medical or 805
http://vip.persianss.ir
10 surgical. If performed within the first 7 weeks of gestation, these beneficial effects of HRT. The Women’s Health Initiative
medical abortion utilizing oral antiprogesterone agents (WHI) stopped the Heart and Estrogen/Progestin Replacement
such as RU486 (Mifepristone) and vaginally administered Study (HERS) trial of combined hormones/estrogen/progestin
Congenital Heart Disease in Adults
misoprostol (prostaglandin E1 analog) are as effective as in women with an intact uterus, because of the increased risk
suction curettage.10-12 Because expulsion and bleeding of breast cancer, stroke and pulmonary embolism. The current
occur at home, the process is not controlled, so the systemic recommendation is neither to begin nor continue HRT for
vasodilation afforded by the PGE could potentially be risky primary or secondary prevention of cardiovascular disease.
for women with Eisenmenger syndrome/primary pulmonary Rather HRT should be limited to the treatment of menopausal
hypertension. Dilation and suction curettage under local symptoms at the lowest effective dosage over the shortest
anesthesia (paracervical block) is the most common method duration possible and continued use should be reevaluated on
employed for first trimester termination. It carries a very a periodic basis.14-16
low complication rate when performed by an experienced Currently, hormone replacement regimens include unop
obstetrician in an operating room rather than in an outpatient posed estrogen or combined estrogen/progestin therapies.15
setting. Unopposed estrogen is not recommended for women who
Dilatation and evacuation of fetus and placenta are have an intact uterus. A systemic estrogen is available in
more frequently used for termination of second-trimester oral or transdermal form with a starting dose of 0.625 mg
pregnancies. With introduction of a small dilator, called of conjugated estrogen or the equivalent recommended
Laminaria, the cervix is slowly dilated. Most of this occurs in dose. Lower doses of estrogen (0.45 mg of conjugated
the first 6 hours, with maximum dilation usually occurring in estrogen) when combined with a progestin (1.5 mg hydroxy-
12 to 24 hour followed by evacuation. The procedure carries a progesterone acetate) have been found to relieve vasomotor
low rate of complications. symptoms and prevent bone loss. The addition of cyclic or
Another method is the intrauterine instillation of of daily progestin administration is recommended for women
prostaglandin (E2 or F) and hypertonic urea that results in with an intact uterus to reduce risk of endometrial cancer.17
uterine contractions and expulsion of the fetus. However, the Progestin (medroxyprogesterone acetate or norethindrone
labor can take up to 20 hours, is painful and requires in-patient acetate) is usually prescribed in oral form, while progesterone
care. There is the risk of retention of the placenta, hemorrhage is available in other forms including oral (micronized), vaginal
and infection. or rectal suppositories.
The decision to prescribe HRT must consider the individual
MENOPAUSE needs of each patient weighing the benefits against the risks.
For the woman with CHD, the decision to prescribe HRT
Menopause is defined as the absence of menses for 12 must take into account her underlying cardiac defect, previous
consecutive months. The number of women with CHD history of surgeries and her present clinical status. Because
who are currently reaching menopause is increasing. As the the standard estrogen replacement dose, is approximately
population of adults continues to grow, the number of women one quarter of the estrogenic potency of the 20 mg of ethinyl
reaching menopause will also increase. Currently, there estradiol in an oral contraceptive pill, the majority of women
are no studies evaluating the patterns of menopause in this with CHD can safely receive these agents.
population, therefore most of our understanding of symptom However, WHI reports a 41 percent increase in stroke and
presentation and management is drawn on population-based a two-fold greater rate of venous thromboembolism (VTE), in
studies. women receiving estrogen plus progestin therapy. Therefore
While women may begin menopausal transition at about HRT use in women at high risk for thrombolic episodes is
47 years, for most women the menopause occurs between 50 discouraged.18 HRT should not be prescribed in women with
and 55 years with an average of 51.13 Symptoms commonly a history of thrombosis, embolism or bleeding.
associated with menopause may develop during this In the absence of clinical data, one should prescribe the
transitional period. Nulliparous women tend to experience lowest dose of systemic HRT that will address the vasomotor
menopause earlier than multiparous women. symptoms associated with estrogen deficiency. If there are
Health providers need to be sensitive to the emotional and residual complaints of vaginal dryness or dyspareunia due
physical effects of menopause and also assist in decisions to vaginal atrophy, the symptoms can be treated with vaginal
regarding hormone replacement therapy (HRT). Estrogen estrogen in the form of cream, tablets or ring. Estrogen doses
production begins to decline over a period of several years lower than 0.625 mg of conjugated estrogen are probably
before complete cessation. The principal goal of HRT is to as effective in reducing bone loss if combined with a
deliver the lowest effective dose of estrogen/progestin to progestin.19,20 For females with cyanotic CHD, or at risk for
relieve menopausal symptoms and to potentially reduce the thromboembolic events, HRT should be contraindicated. For
risk of osteoporosis. these women, over-the-counter phytoestrogens or selective
806 While earlier reports emphasized the benefits of HRT for serotonin reuptake inhibitors (SSRI) may be an alternative
prevention of coronary artery disease, later reports questioned to alleviate menopausal symptoms such as hot flashes.
There are mixed reports of their effectiveness from controlled Aangeboren Hartafwijking (ZAHARA) II study. Am Heart J.
2011;161:269-75.
56
trials. In the asymptomatic female, it is reasonable to avoid
HRT and utilize other agents such as bisphosphonates to 8. Pritchard J. Changes in the blood volume during pregnancy
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
and delivery. Anesthesiology. 1965;26:393-9.
prevent osteoporosis, unless the latter are contraindicated due
9. Kaneshige E. Serum ferritin as an assessment of iron stores
to reflux, hiatal hernia or impaired renal function. Transvaginal and other hematologic parameters during pregnancy. Obstet
estrogen may then be used for vaginal atrophy and SSRIs for Gynecol. 1981;57:238-42.
mood changes associated with the perimenopause or early 10. Ueland K, Hansen J. Maternal cardiovascular dynamics II:
menopause.19 posture and uterine contractions. Am J Obstet Gynecol. 1969;
101:1-7.
CONCLUSION 11. Ueland K, Metcalfe J. Circulatory changes in pregnancy.
Clinical Obstet Gynecol. 1975;18:41-50.
Gynecologic issues such as DUB, remains one of the 12. Christianson RE. Studies on blood pressure during pregnancy.
1. Influence on parity and age. Am J Obstet Gynecol.
commonest reasons for women with CHD to seek medical
1976;125:509-13.
attention. As the population of women with CHD increases, 13. Ueland K, Parer JT. Effects of estrogens on the cardiovascular
menopause will need to be addressed. Detailed work-up of system of the ewe. Am J Obstet Gynecol. 1966;96:400-6.
these patients along with counseling/education is needed 14. Kerr M. The mechanical effects of the gravid uterus in late
in order to establish a diagnosis and prescribe appropriate pregnancy. J Obstet Gynaecol Br Commonw. 1965;72:513-29.
management in the setting of their particular cardiac 15. Kinsella S, Lohmann G. Supine hypotensive syndrome. Obstet
physiology. Gynecol. 1994;83:774-88.
16. Ueland K, Hansen J. Maternal cardiovascular dynamics III:
A wise man should consider that health is the greatest of labor and delivery under local and caudal anesthesia. Am J
Obstet Gynecol. 1969;103:8-18.
human blessings, and learn how by his thought to derive
17. Ueland K, Novy M, Peterson E, et al. Maternal cardiovascular
benefit from his illnesses. dynamics IV: the influence of gestational age on the maternal
—Hippocrates cardiovascular response to posture and exercise. Am J Obstet
Gynecol. 1969;104:856-8.
REFERENCES 18. Cutforth R, MacDonald CB. Heart sounds and murmurs in
pregnancy. Am Heart J. 1966;71:741-7.
19. Hurst JW, Staton J, Hubbard D. Precordial murmurs during
Pregnancy in Women with CHD pregnancy and lactation. N Engl J Med. 1958;259:515-7.
20. Romano-Zeleka O, Hirsh R, Blieden L, et al. The risk of
1. Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C,
congenital heart defects in offspring of individuals with
et al. ESC Guidelines on the management of cardiovascular
congenital heart defects. Clin Genet. 2001;59:325-9.
diseases during pregnancy: the Task Force on the Management
21. ACOG practice bulletin number 77. Obstet Gynecol.
of Cardiovascular Diseases during Pregnancy of the European
2007;109:217-27.
Society of Cardiology (ESC). Eur Heart J. 2011;32:3147-97.
22. Eddleman KA, Malone FD, Sullivan L, et al. Pregnancy loss
Epub 2011 Aug 26.
rates after midtrimester amniocentesis. Obstet Gynecol. 2006;
2. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008
108:1067-72.
Guidelines for the Management of Adults with Congenital
23. Sharland G. Routine fetal cardiac screening: what are we
Heart Disease: Executive Summary: a report of the American
doing and what should we do? Prenat Diagn. 2004;24:
College of Cardiology/American Heart Association Task
1123-9.
Force on Practice Guidelines (writing committee to develop
24. Upham M, Medoff-Cooper B. What are the responses and
guidelines for the management of adults with congenital heart
needs of mothers of infants diagnosed with congenital heart
disease). Circulation. 2008;118:2395-451. Epub 2008 Nov 7.
disease? MCN Am J Matern Child Nurs. 2005;30:24-9
3. Presbitero P, Somerville J, Stone S, et al. Pregnancy in cyanotic
25. Siu S, Sermer M, Harrison D, et al. Risk and predictors for
heart disease. Circulation. 1994;89:2673-6.
pregnancy-related complications in women with heart disease.
4. Bailey LB, Berry RJ. Folic acid supplementation and the
Circulation. 1997;96:2789-94.
occurrence of congenital heart defect, orofacial clefts, multiple
26. Siu S, Sermer M, Colman J, et al. Prospective multi-center
births and miscarriages. Am J Clin Nutr. 2005. 81:1213 S-17S.
study of pregnancy outcomes in women with heart disease.
5. Metcalfe J, Ueland K. Maternal cardiovascular adjustments to
Circulation. 2001;104:515-21.
pregnancy. Progress in cardiovascular diseases. 1974;16:363-
27. Drenthen W, Boersma E, Balci A, et al. ZAHARA Investigators.
74.
Predictors of pregnancy complications in women with
6. Ueland K. Maternal cardiovascular dynamics VII:
congenital heart disease. Eur Heart J. 2010;31:2124-32. Epub
intrapartum blood volume changes. Am J Obstet Gynecol.
2010 Jun 28.
1976;126:671-7.
28. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. ZAHARA
7. Balci A, Sollie KM, Mulder BJ, et al. Associations between
Investigators. Outcome of pregnancy in women with congenital
cardiovascular parameters and uteroplacental Doppler (blood)
heart disease: a literature review. J Am Coll Cardiol. 2007 Jun
flow patterns during pregnancy in women with congenital 807
19;49:2303-11. Epub 2007 Jun 4.
heart disease: Rationale and design of the Zwangerschap bij
http://vip.persianss.ir
10 29. Perloff JK, Marelli AJ. Perloff’s Clinical Recognition of
Congenital Heart Disease, 6th edition. Philadelphia: WB
47. Vriend JWJ, Drenthen W, Pieper PG, et al. Outcome of
pregnancy after repair of aortic coarctation. Eur Heart J. 2005;
Saunders; 2012. 26:2173-8.
Congenital Heart Disease in Adults
30. Chugh R. Caring for the adult with congenital heart disease: 48. Roberts JM, Pearson GD, Cutler JA, et al. Summary of the
Management of common defects. The Permanente Journal. NHLBI Working Group on Research on Hypertension During
2007;11:40-6. Pregnancy. Hypertens Pregnancy. 2003;22:109-27.
31. Zuber M, Gautschi N, Oechslin E, et al. Outcome of pregnancy 49. Veldtman GR, Connolly HM, Grogan M, et al. Outcome
in women with congenital shunt lesions. Heart. 1999;81: of pregnancy in women with tetralogy of Fallot. J am Coll
271-5. Cardiol. 2004;44:174-80.
32. Yap SC, Drenthen W, Meijboom FJ, et al. ZAHARA 50. Singh H, Bolton PJ, Oakley CM. Pregnancy after surgical
investigators. Comparison of pregnancy outcomes in women correction of tetralogy of Fallot. Br Med J (Cl Res Ed.) 1982;
with repaired versus unrepaired atrial septal defect. BJOG. 285:168-70.
2009;116:1593-601. Epub 2009 Aug 13. 51. Neumayer U, Somerville J. Outcome of pregnancies in patients
33. Yap SC, Drenthen W, Pieper PG, et al. ZAHARA investigators. with complex pulmonary atresia. Heart. 1997;78:16-21.
Pregancy outcome in women with repaired versus unrepaired 52. Connolly HM, Warnes CA. Outcome of pregnancy in patients
ventricular septal defect. BJOG. 2010;117:683-9. Epub 2010 with complex pulmonic valve atresia. Am J Cardiol. 1997;79:
Feb 15. 519-21.
34. Actis Dato G, Cavaglia M, Aidala E, et al. Patent ductus 53. Drenthen W, Pieper PG, Zoon N, et al. Pregnancy after
arteriosus. Follow-up of 677 operated cases 40 years later. biventricular repair for pulmonary atresia with ventricular
Minerva Cardioangiol. 1999;47:245-54. septal defect. Am J Cardiol. 2006;98:262-6.
35. Drenthen W, Pieper PG, van der Tuuk K, et al. ZAHARA 54. Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for
Investigators. Cardiac complications relating to pregnancy arrhythmias and sudden cardiac death late after repair of tetral-
and recurrence of disease in the offspring of women with ogy of Fallot: a multicentre study. Lancet. 2000;356:975-81
atrioventricular septal defects. Eur Heart J. 2005;26:2581-7. 55. Kim WH, Seo JW, Kim SJ, et al. Aortic dissection late after
Epub 2005 Aug 17. repair of tetralogy of Fallot. Int J Cardiol. 2005;101:515-6.
36. Hameed A, Karaalp IS, Tummala PP, et al. The effect of valvular 56. Rathi VK, Doyle M, Williams RB, et al. Massive aortic
heart disease on maternal and fetal outcome of pregnancy. J root aneurysm and dissection in repaired tetralogy of Fallot;
Am Coll Cardiol. 2001;37:893-9. diagnosis of cardiac magnetic resonance imaging. Int J Cardiol.
37. Hameed AB, Goodwin TM, Elkayam U. Effect of pulmonary 2005;101:169-70.
stenosis on pregnancy outcomes—a case-control study. Am 57. Kamiya CA, Iwamiya T, Neki R, et al. Outcome of pregnancy
Heart J. 2007;154:852-54. Epub 2007 Sep 6. and effects on the right heart in women with repaired tetralogy
38. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Non-cardiac of Fallot. Circ J. 2012;76:957-63. Epub 2012 Jan 25.
complications during pregnancy in women with isolated 58. Balci A, Drenthen W, Mulder BJ, et al. Pregnancy in women
congenital pulmonary valvar stenosis. Heart. 2006; 92:1838- with corrected tetralogy of Fallot: occurrence and predictors of
43. adverse events. Am Heart J. 2011;161:307-13. Epub 2011 Jan
39. Silversides CK, Coleman JM, Sermaer M, et al. Early and 15.
intermediate-term outcomes of pregnancy with congenital 59. Meijer JM, Pieper PG, Drenthen W, et al. Pregnancy, fertility,
aortic stenosis. Am J Cardiol. 2003;91:1386-9. and recurrence risk in corrected tetralogy of Fallot. Heart.
40. Tzemos N, Silversides CK, Colman JM, et al. Late cardiac 2005;91:801-5
outcomes after pregnancy in women with congenital aortic 60. Gelson E, Gatzoulis M, Steer PJ, et al. Tetralogy of Fallot:
stenosis. Am Heart J. 2009;157:474-80. maternal and neonatal outcomes. BJOG 2008;115:398-402.
41. Yap SC, Drenthen W, Pieper PG, et al. ZAHARA investigators. 61. Naguib MA, Dob DP, Gatzoulis MA. A functional
Risk of complications during pregnancy in women with understanding of moderate to complex congenital heart disease
congenital aortic stenosis. Int J Cardiol. 2008;126:240-6. Epub and the impact of pregnancy. Part II: tetralogy of Fallot,
2007 May 4. Eisenmenger's syndrome and the Fontan operation. Int J Obstet
42. Elkayam U, Bitar F. Valvular heart disease and pregnancy part Anesth. 2010;19:306-12. Epub 2010 Jun 3. Review.
I: native valves. J Am Coll Cardiol. 2005;46:223-30. Review. 62. Canobbio MM, Morris CD, Graham TP, et al. Pregnancy
43. Niwa K, Perloff Jk, Bhuta SM, et al. Structural abnormalities outcomes after atrial repair for transposition of the great
of the great arterial walls in congenital heart disease: light and arteries. Am J Cardiol. 2006;98:668-72.
electron microscopic analyses. Circulation. 2001;103:393-400. 63. Clarkson PM, Wilson NJ, Neutze JM, et al. Outcomes of
44. Saidi AS, Bezold LI, Altman CA, et al. Outcome of pregnancy pregnancy after the Mustard operation for transposition of the
following intervention for coarctation of the aorta. Am J great arteries with intact ventricular septum. J Am Coll Cardiol,
Cardiol. 1998;82:786-8. 1994;24:190-3.
45. Kreiger EV, Landzberg MJ, Economy KE, et al. Comparison 64. Genoni M, Jenni R, Hoerstrup, et al. Pregnancy after atrial repair
of risk of hypertensive complications of pregnancy among for transposition of the great arteries. Heart. 1991;81: 276-7.
women with versus without coarctation of aorta. Am J Cardiol. 65. Guedes A, Mercier LA, Leduc L, et al. Impact of pregnancy on the
2011;107:1529-34. systemic right ventricle after a Mustard operation for transposition
46. Beauchesne LM, Connolly HM, Ammash NM, et al. of the great arteries. J Am Coll Cardiol. 2004; 44:433-7.
Coarctation of the aorta: Outcome of pregnancy. J Am Coll 66. Drenthen W, Pieper PG, Ploeg M, et al. Risk of complications
808
Cardiol. 2001;38:1728-33. during pregnancy after Senning or Mustard (atrial) repair of
complete transposition of the great arteries. Eur Heart J. 2005;
26:2588-95.
86. Pocock SB, Chen KT. Inappropriate use of antibiotic
prophylaxis to prevent infective endocarditis in obstetric
56
67. Metz TD, Jackson GM, Yetman AT. Pregnancy outcomes patients. Obstet Gynecol. 2006;108:280-5.
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
in women who have undergone an atrial switch repair for 87. Ellison J, Walker ID, Greer IA. Antenatal use of enoxaparin for
congenital d-transposition of the great arteries. Am J Obstet prevention and treatment of thromboembolism in pregnancy.
Gynecol. 2011;205:273.e1-75. Epub 2011 Jun 17. British Journal of Obstetrics and Gynaecology. 2000;107:
68. Tobler D, Fernandes SM, Wald RM, et al. Pregnancy outcomes 1116–21.
in women with transposition of the great arteries and arterial 88. Sadler L, McCowan, White H, et al. Pregnancy outcomes and
switch operation. Am J Cardiol. 2010;106:417-20. cardiac complications in women with mechanical, bioprosthetic
69. Connolly HM, Grogan M, Warnes CA, et al. Pregnancy among and homograft valves. BJOG. 2000;107:245-53.
women with congenitally corrected transposition of the great 89. Nassar AH, Hobeika EM, Abd Essamad HM, et al. Pregnancy
arteries. J Am Coll Cardiol. 1999;33:1692-5. outcome in women with prosthetic heart valves. Am J of Obstet
70. Therrien J, Barnes I, Somerville J. Outcome of pregnancy in Gynecol. 2004;191:1009-13.
patients with congenitally corrected transposition of the great 90. Seshadri N, Goldhaber SZ, Elkayam U, et al. The clinical
arteries. Am J Cardiol. 1999;84:820-4. challenge of bridging anticoagulation with low molecular-
71. Dobb DP, Naquib MA, Gatzoulis MA. A functional weight heparin in patients with mechanical valves : an evidence
understanding of moderate to complex congenital heart based comparative review focusing on anticoagulation
disease and the impact of pregnancy. Part I: the transposition options in pregnant and nonpregnant patients. Am Heart J.
complexes. Int J Obstet Anesth. 2010;19:298-305. Review. 2005;150:27-34.
72. Connolly HM, Warnes CA. Ebstein’s anomaly: Outcome of 91. Bates S, Greer IA, Hirsh J, et al. Use of Antithrombotic agents
pregnancy. J Am Coll Cardiol. 1994;23:1194-8. during pregnancy. Chest. 2004;126:627S-44S.
73. Donnelly JE, Brown JM, Radford DJ. Pregnancy outcome and 92. Elkayam U, Singh H, Irani A, et al. Anticoagulation in pregnant
Ebstein's anomaly. Br Heart J. 1991;66:368-71. women with prosthetic heart valves. J Cardiovasc Pharmacol
74. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. Ther. 2004;9:107-15. Review.
1971;26:240-8. 93. Elkayam U, Goland S. The search for a safe and effective
75. Canobbio MM, Mair DD, Ven der Velde M, et al. Pregnancy anticoagulation regimen in pregnant women with mechanical
outcomes after Fontan repair. J Am Coll Cardiol. 1996;28: prosthetic heart valves. J Am Coll Cardiol. 2012;59:
763-7. 1116-8.
76. Drenthen W, Pieper PG, van der Tuuk K, et al. Pregnancy 94. Goland S, Elkayam U. Anticoagulation in pregnancy. Cardiol
and delivery in women after Fontan palliation. Heart. 2006; Clin. 2012;30:395-405.
92:1290-4. 95. Elefteriades JA. Natural history of thoracic aortic aneurysms:
77. Gleicher N, Midwall J, Hichberger D, et al. Eisenmenger’s indications for surgery, and surgical versus nonsurgical risks.
syndrome and pregnancy. Obstet Gynecol Surv. 1979;34: Ann Thorac Surg. 2002;74:S1877-80. (discussion S 1892-98).
721-41. 96. Davies RR, Goldstein LJ, Coady, et al. Yearly rupture
78. Katsuragi S, Yamanaka K, Neki R, et al. Maternal Outcome or dissection rates for dissection rates for thoracic aortic
in Pregnancy Complicated With Pulmonary Arterial aneurysms: simple prediction based on size. Ann Thorac Surg.
Hypertension. Circ J. 2012 Jun 13. 2002;73:17-27 (discussion 27-28).
79. Avila WS, Grinberg M, Snitcowsky R, et al. Maternal and fetal 97. Hiratzka LF, Bakris GL, Beckman JA, et al. ACCF/AHA/
outcome in pregnant women with Eisenmenger's syndrome. AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for
Eur Heart J. 1995;16:460-4. the diagnosis and management of patients with thoracic aortic
80. Weiss BM, Zemp L, Seifert B, et al. Outcome of pulmonary disease. J Am Coll Cardiol. 2010; 55:e27-e129.(Key algorithm
vascular disease in pregnancy: a systematic overview from is on page e83).
1978 through 1996. J Am Coll Cardiol. 1998;31:1650-7. 98. Shotan A, Ostrzega E, Mehra A, et al. Incidence of arrhythmias
Review. in normal pregnancy and relation to palpitations, dizziness, and
81. Wang H, Zhang W, Liu T. Experience of managing pregnant syncope. Am J Cardiol. 1997;79:1061-4.
women with Eisenmenger's syndrome: maternal and fetal 99. Baumgartner H. Reproductive issues in adults with congenital
outcome in 13 cases. J Obstet Gynaecol Res. 2011;37:64-70. heart disease: arrhythmias during pregnancy: importance,
82. Goodwin TM, Gherman RB, Hameed A, et al. Favorable diagnosis and therapy. Thorac Cardiovasc Surg. 2001;49:94-7.
response of Eisenmenger syndrome to inhaled nitric oxide during Review.
pregnancy. Am J Obstet Gynecol. 1999;180: 64-7. 100. Lee J CR, Wetzel G, Shannon K. Maternal arrhythmia
83. Rosenthal E, Nelson-Piercy C. Value of inhaled nitric oxide management during pregnancy in patients with structural
in Eisenmenger syndrome during pregnancy. Am J Obstet heart disease. Progress in Pediatric Cardiology. 2004;19:
Gynecol. 2000;183:781-2. 71-82.
84. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective 101. Chugh R. Management of pregnancy in patients with congenital
endocarditis: guidelines from the American Heart Association: heart disease and systemic ventricular failure. Progress in
a guideline. Circulation. 2007 Oct 9;116:1736-54. Epub 2007 Pediatric Cardiology. 2004;19:47-60.
Apr 19. Erratum in: Circulation. 2007;116:e376-7. 102. Frishman WH, Elkayam U, Aronow WS. Cardiovascular
85. Nahum GG, Uhl K, Kennedy DL. Antibiotic use in pregnancy drugs in pregnancy. Cardiol Clin. 2012;30:463-91. Epub 2012
and lactation. Obstet Gynecol. 2006;107:1120-38. Jun 5.
809
http://vip.persianss.ir
10 103. Wesseling J, van Driel D, Heymans HAS, et al. Coumarins
during pregnancy: long term effects on growth and
6. Centers for Disease Control and Prevention. U.S. Medical
Eligibility Criteria for Contraceptive Use, 2010. MMWR
development in school age children. Thromb Haemostas. Recomm Rep. 2010;59:1-86.
Congenital Heart Disease in Adults
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
11. ACOG. Clinical management guidelines of obstetrician- Health Initiative randomized controlled trial. JAMA.
gynecologists. Medical management of abortion. Obstet 2002;288:321-33.
Gynecol. 2005;106:871-82. 17. Furness S, Roberts H, Marjoribanks J, et al. Hormone therapy
12. Mischell DR. Family planning: contraception, sterilization, in postmenopausal women and risk of endometrial hyperplasia.
and pregnancy termination. In: Katz VL, Lentz GM, Lobo Cochrane Database of Systematic Rev 2009.(2):CD000402.
RA, Gershenson DM (Eds) Comprehensive Gynecology, 5th DOI: 10.1002/14651858.CD000402.pub3
edition. Philadelphia, PA: Mosby Elsevier; 2007. 18. The Women’s Health Initiative Steering Committee. Effects
13. Lund KL. Menopause and the Menopausal Transition. Medical of conjugated equine estrogen in postmenopausal women with
Clinics of North America. 2008;92:1253-71. hysterectomy. The Women’s Health Initiative randomized
14. Position Statement. The 2012 Hormone Therapy Position controlled trial. JAMA. 2004;291:1701-12.
Statement of The North American Menopause Society. 19. Sikon A, Thacker HL. Treatment options for menopausal
Menopause: The Journal of the North American Menopause hot flashes. Cleveland Clinic Journal of Medicine. 2004;71:
Society. 2012;19:257-71. 578-82.
15. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and 20. Utian WH, Shoupe D, Bachmann G, et al. Relief of vasomotor
benefits of estrogen plus progestin in healthy postmenopausal symptoms and vaginal atrophy with lower doses of conjugated
women: principal results From the Women’s Health Initiative equine estrogens and medroxyprogesterone acetate. Fertil
randomized controlled trial. JAMA. 2002;288:321-33. Steril. 2001;75:1065-79.
811
http://vip.persianss.ir
Exercise and Sports in
C hapter
ExErcisE and sports in adolEscEnts and adults with congEnital hEart disEasE
Type of exercise Isotonic Isometric
Effect on the heart Volume load Pressure load
Blood pressure Increase in systolic and decrease in Sudden increase is systolic blood
diastolic pressure pressure
Heart rate +++ +
Stroke volume +++ +
Cardiac output +++ +
Oxygen consumption +++ +
Legend: +++ significant increase; + limited increase.
813
http://vip.persianss.ir
10 ATHLETIC AND COmpETITIvE SpORTS Ambulatory Holter and Event Recording
The 36th Bethesda conference guidelines define the For arrhythmias that occur sporadically or are affected by
congEnital hEart disEasE in adults
competitive athlete “as one who participates in an organized changes in the hemodynamic status, serial electrocardiographic
team or individual sport that requires regular competition recordings may be required over time. Depending upon the
against others as a central component, places a high premium frequency and duration of these arrhythmias, an ambulatory
on excellence and achievement and requires some form of Holter monitor or transtelephonic event recorder may be
systematic (and usually intense) training.” These highly helpful.
intense organized competitive sports are likely to put heavy A recent study by Rodriguez et al showed that 15 percent
emotional and physical pressures on the athlete. In a person of the adults with CHD had arrhythmias on Holter monitoring.
with CHD, commitment to competitive sports may not allow Repeat Holter monitoring detected a new arrhythmia in
him/her to determine when it is prudent to terminate the 34 percent of the patients. The majority of the patients with
physical exertion if cardiac-related symptoms or warning arrhythmias were asymptomatic (76%). Among those with
signs occur.7 normal ECGs, arrhythmias were frequently detected on Holter
monitoring (26%).16
SUDDEN CARDIAC DEATH IN ATHLETES
Implantable Loop Recorder
The most commonly reported congenital heart or genetically-
linked lesions associated with sudden cardiac death (SCD) An implantable loop recorder is a small device to help identify
during sports participation are hypertrophic cardiomyopathy the causes of unexplained syncope. Under local anesthesia, it
(HCM), coronary artery anomalies, Marfan syndrome and is inserted under the skin below the clavicle, usually on the
aortic valve disease.8-10 left side with closer proximity to the heart. It continuously
Sudden cardiac death is less frequently linked with the records heart rhythm for up to 2 years. When syncope occurs,
underlying diagnosis of complex congenital heart defects such the device is activated to save the recording before, during
as tetralogy of Fallot, D-transposition of the great arteries, and after the episode. These recordings are then examined to
congenitally corrected transposition of the great arteries or determine if there are any tachy or bradyarrhythmias causing
defects associated with significant pulmonary hypertension. syncope.17
More often than not these individuals are prudent regarding
exercise prescriptions and restrictions. Treadmill Stress Testing
CARDIAC DIAGNOSTIC TESTING FOR SCREENING Treadmill stress testing allows objective assessment of the
functional capacity, exercise-induced arrhythmias and impact
Besides a good history and physical examination that are of of exercise on the QT interval. In addition, it is most commonly
utmost importance,11 the following cardiac tests may assist in used to evaluate ischemia. Regular organized exercise over
identifying individuals at higher risk for SCD. several months, in children and adolescents with CHD, has
beneficial effects on physical fitness and improves objectively
Electrocardiogram assessed functional capacity.18
Patients with coarctation of aorta (CoA) should have blood
For population-based preparticipation screening of cardio- pressure measurements checked in the right arm and leg before
vascular diseases in young athletes, the 12-lead ECG has been and after exercise. The resting systolic blood pressure readings
advocated as a practical and cost-effective tool.12 Although, the and resting systolic blood pressure difference between the
likelihood of ECG abnormality associated with HCM is high right arm and leg are not indicators for blood pressure response
(75–95%), other findings such as a prolonged QT in individuals during exercise. Exercise testing is very important in patients
with the long QT syndrome or ST and T wave abnormalities with CoA to unmask the exercise-induced hypertension.19,20
suggestive of coronary artery anomalies in the young or other Those with cyanotic CHD should have their oxygen
specific findings associated with inherited syndromes, may saturation checked at rest and after at treadmill stress test
not be consistently present on serial ECGs.13,14 ECGs may or before and after a six-minute walk test. Few centers
sometimes be helpful in identifying Brugada syndrome15 and have bicycle stress testing that may allow more convenient
other inherited syndromes that may place the person at a risk measurements of ECG, blood pressure and workload in people
for a high risk for SCD secondary to ventricular tachycardia/ with back problems, but this form of testing may be limited
fibrillation, under adrenergic stimulation. due to leg fatigue.
814
Echocardiography Stress Echocardiography 57
Transthoracic echocardiography (2-dimensional, color and In addition to the assessment of symptomatic and functional
ExErcisE and sports in adolEscEnts and adults with congEnital hEart disEasE
spectral Doppler) is the principal diagnostic imaging modality response to exercise, stress echocardiography provides
for clinical identification of structural heart diseases and valuable information on exercise-induced changes in
serial follow-up of residua and sequelae in individuals with hemodynamics, ventricular function and pulmonary artery
unoperated or operated CHD.21,22 pressure in adolescents and adults with CHD.
The most common cause of sudden cardiac death in the Biventricular response to exercise, changes in pulmonary
young is hypertrophic cardiomyopathy (HCM). A heart pressure and hemodynamic severity of the underlying defect
murmur or abnormalities on ECG may be suggestive of classic before and after exercise offers an additional prognostic value
hypertrophic cardiomyopathy or its variants (Figures 1 and 2). for clinical management.
The diagnosis is usually confirmed by echocardiography.
The presence of unexplained asymmetric left ventricular Cardiopulmonary Exercise Testing
(LV) wall thickening with a maximal LV end-diastolic wall
thickness of 15 mm or more in an adult (two or more standard Where available and affordable, cardiopulmonary exercise
deviations from the mean relative to body surface area; z-score testing (CPET) may offer additional prognostic information by
of two or more in children) is considered diagnostic for comparing peak oxygen uptake (peak VO2) of the individual,
HCM.23,24 However, when an echocardiogram is performed in relation to the defined normal values that are greater than 90
in a person who has a mutant HCM gene, but is younger than percent of the predicted peak VO2.26
14 years of age, the left ventricular wall thickness may not Kempny et al. reviewed 23 publications, with 2286
meet the criteria for HCM because he or she is in the pre- patients from the Medline literature, describing exercise
hypertrophic phase of the disease process.23 Therefore, capacity in adults with CHD using CPET. They then included
throughout adolescence annual serial echocardiography is 2129 patients who underwent CPET at the Royal Brompton
recommended in HCM family members.23,25,26 Hospital in London, U.K. They observed that 80 percent of
The second most common cause of sudden cardiac death patients had reduced peak oxygen uptake compared with
in athletes is a coronary artery anomaly. On a good quality normal values. There were significant differences in peak VO2
transthoracic (2-dimensional and color) echocardiogram, between subgroups of adults with CHD. Even adults with
the origin and proximal courses of the anomalous coronary simple CHDs, on an average, had significantly reduced peak
arteries may be visualized in the parasternal short-axis views. VO2 compared with normal values. Adults with Eisenmenger
815
http://vip.persianss.ir
10
congEnital hEart disEasE in adults
syndrome and complex CHD had the lowest values. This study the pulsatile aorta and the pulmonary artery post-exercise and
allowed comparisons in the exercise capacity of individual prove fatal.28,29 These individuals may present with exertional
and their peers. The data obtained from this study should be syncope, chest pain or palpitations and surgical correction is
helpful in interpreting CPET results, guiding therapy, and primarily indicated in symptomatic patients or when ischemia
advising patients on activities of daily living, participation in is demonstrated on imaging.
sports and choice of occupation.27 Another coronary anomaly associated with SCD is the
anomalous left coronary artery arising from the pulmonary
Coronary Computed Tomography Angiography artery (ALCAPA). Long-term outcomes in undiagnosed or
unoperated cases depend on whether or not the degree of
Coronary computed angiography (CTA) is now a popular and collateralization adequately compensates for myocardial
relatively inexpensive imaging tool for definitive identification ischemia, its impact on left ventricular function, the severity
of congenital coronary artery anomalies. Due to the heavy of mitral regurgitation due ischemic papillary muscle and risk
exposure to radiation in a young person and the possibility of of ventricular arrhythmias caused by myocardial scarring
an allergic reaction to the iodine contrast agent, this diagnostic due to ischemia. Surgery to correct this anomaly should be
test is used prudently. performed by implantation of the origin of the left coronary
CTA is usually recommended when congenital coronary artery into the aortic root or a bypass operation. Following
artery anomalies are suspected, as in the case of young revascularization, stress testing is performed periodically to
people presenting with exertional syncope or palpitations evaluate exercise tolerance, ischemia and exercise-induced
due to ventricular arrhythmias. Unfortunately, this diagnosis arrhythmias before recommending level of exercise.
is often missed during life since many young people may be A very rare form of anomalous coronaries are the
asymptomatic with daily activities and have a normal resting congenitally hypoplastic coronary arteries. The risk of
ECG. sudden death increases during the growth phase, as the
More commonly, congenital coronary abnormalities present myocardial demands outstrip the coronary blood supply.
with anomalous origins from the wrong sinuses. The more Unfortunately, an adolescent may suffer sudden cardiac
common type is the anomalous right coronary artery arising death in sleep or during routine activity, with or without any
from the left coronary sinus (ARCA). The most dangerous premonitory symptoms such as palpitations and/or light-
type is the anomalous left main coronary artery (ALMCA) headedness. Sometimes serial electrocardiograms may show
originating from the right (anterior) sinus of Valsalva. The subtle nonspecific ST and T wave abnormalities (Figures 3A
ALMCA takes an acute angled bend with a course between and B). Although not stated in the guidelines, our personal
816 the right ventricular outflow tract/pulmonary trunk and the experience guides us to admit an individual for a complete
anterior aspect of the aorta, that can get compressed between diagnostic work up and potential treatment, if there are
57
ExErcisE and sports in adolEscEnts and adults with congEnital hEart disEasE
a
B
Figures 3a and B: Serial electrocardiograms showing ischemic changes in a 19-year-old man with hypoplastic coronaries. Echocardiogram
showed borderline to mild left ventricular dilatation and normal left ventricular systolic function. He suffered sudden cardiac death due to
ventricular arrhythmias during normal activities
sporadic symptoms accompanied by subtle ECG changes and/ desirable imaging tool for several pathologies. Where it is
or mild left ventricular dilatation even when the left (systemic) available and when it is affordable, it may be used judiciously
ventricular systolic function is normal. for clarifying the diagnosis in suspected cases of HCM, by
demonstrating segmental areas of hypertrophy of the left
magnetic Resonance Imaging ventricle (such as in the anterolateral free wall or apex).30,31
Arrhythmogenic right ventricular cardiomyopathy or
Magnetic resonance imaging (MRI) does not expose a person dysplasia (ARVC/ARVD) is among the common causes of 817
to ionizing radiation and provides a good contrast between SCD in the young, with an incidence that is actually higher
the soft tissues of the heart and blood vessels, making it a than previously reported.
http://vip.persianss.ir
10
congEnital hEart disEasE in adults
Figure 4: 50-year-old man with Brugada syndrome (Type 1 pattern) presenting with a history of short episodes of presyncope
ExErcisE and sports in adolEscEnts and adults with congEnital hEart disEasE
GENERAL CONSIDERATIONS ion channel diseases, they commonly occur with CHD
restricting participation in exercise and sports programs.
Adolescents and adults receiving anticoagulation should not There is specific prognostic importance linked with the
participate in any type of contact sport. All sport activities and arrhythmias and CHDs, because the main determinant for
exercise have to be avoided during active infection with fever assessing sports participation in patients with arrhythmias
associated with subacute bacterial endocarditis. is the presence of structural heart disease. The Study
The main determinants of exercise tolerance besides Group on Sports Cardiology, of the European Association
the severity of the underlying CHD lesions are ventricular for Cardiovascular Prevention and Rehabilitation, has
function, pulmonary hypertension, cyanosis and arrhythmias. made comprehensive recommendations for participation
in leisure-time physical activity and competitive sports, in
ventricular Function patients with arrhythmias and potentially arrhythmogenic
conditions.39,40
Cardiovascular conditioning has a positive benefit on the
ventricular function which in turn affects exercise tolerance.
An annual assessment of ventricular function should be DEFECT-SpECIFIC EXERCISE RECOmmENDATIONS
performed for risk stratification of all patients with CHD who
have complex defects, unoperated or operated. Less frequent Shunt Lesions
assessment (every other year) may be performed in those with
simple operated CHD and no significant residua or sequelae. Atrial Septal Defect (ASD)
An ejection fraction (EF) over 50 percent allows full
participation in sports while an EF less than 40 percent limits No exercise restrictions
participation in competitive sports. • Unoperated patient with a small to moderate ASD,
with a left-to-right shunt, without significant right
pulmonary Hypertension heart enlargement and not more than mild pulmonary
hypertension with an estimated right ventricular
In day-to-day practice, the peak pulmonary artery systolic systolic pressure (RVSP) less than 45 mm Hg on
pressure (PASP), is assessed by echocardiography based on the echocardiography.
estimation of the right ventricular systolic pressure (RVSP). • Postsurgical or device closure of an ASD (over 6
In the presence of tricuspid regurgitation (TR) by color-flow months ago) without a residual shunt or significant right
Doppler imaging, the RVSP is calculated from the peak velocity heart enlargement and not more than mild pulmonary
(V) of the TR jet (4 V2 + estimated right atrial pressure). The hypertension (estimated RVSP less than 45 mm Hg).
TR jet can be enhanced by injecting saline through a peripheral
intravenous catheter.38 Severe pulmonary hypertension poses a Restriction for athletics
risk of SCD during sports and heavy exertional activities. ASD—operated or unoperated with associated
While there are no restrictions for participation in sports • Severe RV enlargement or decreased function
based on a PASP of less than 30 mm Hg, those with mild • Moderate to severe pulmonary hypertension (estimated
(30–45 mm Hg), moderate (45–60 mm Hg) or severe (greater RVSP is over 45 to 60 mm Hg)
than 60 mm Hg) pulmonary hypertension should be guided on • Uncontrolled arrhythmias (atrial fibrillation/flutter)
an individual basis regarding exercise. • Ventricular tachyarrhythmias
• High degree (second- or third-degree) atrioventricular
Cyanosis (AV) heart block.
Unoperated patients with cyanotic CHD have self limited Ventricular Septal Defect (VSD)
exercise abilities since the cyanosis worsens with effort due to
increasing hypoxemia (decrease in oxygen saturations measured No exercise restrictions
by pulse oximetry). Even after palliative procedures that relieve • Operated VSD (more than 6 months ago) with no residual
the cyanosis at rest, exercise tolerance may still be depressed shunts
due to hypoxemia with moderate to heavy exercise. In the • Unoperated small restrictive VSD, with normal ventricular
absence of a moderate to severe decrease in ventricular function function and absence of pulmonary hypertension (estimated
or tachyarrhythmias associated with impaired consciousness, RVSP is less than 25 mm Hg)
these patients may perform low intensity exercise as long as the • Absence of any atrial or ventricular arrhythmias or high 819
oxygen saturations are maintained over 80 percent. degree AV heart block.
http://vip.persianss.ir
10 Restriction for athletics cardiac death. A fall in blood pressure during exercise is
VSD with large left-to-right shunt a poor prognostic sign. The risk of developing arrhythmias
• Isometric exercises should be avoided since it may lead to should be assessed by an ECG or Holter study.
congEnital hEart disEasE in adults
ExErcisE and sports in adolEscEnts and adults with congEnital hEart disEasE
gradients. Prior to getting involved with athletics, cardiac aorta (especially proximal to the coarctation) in unoperated and
intervention with balloon valvuloplasty, or cardiac surgery operated patients with CoA. Multiple factors including altered
are indicated in symptomatic patients with a gradient greater vascular biology and reduced precoarctation aortic distensibility
than 50 mm Hg. Postoperatively, the individual should contribute to this phenomenon, despite resolution of the local
resume sports after three months.7 Isolated congenital PR obstruction by surgery or implantation of an endovascular stent.
may occur due to an absent pulmonary valve or in association Ambulatory hypertension is common in this population
with PS. even in individuals who are normotensive at rest. Exercise
stress testing helps in risk stratification before exercise
No restrictions counseling and directing appropriate medical management for
• Mild PS with normal RV function better blood pressure control.43
• Operated PS with less than mild residual PS or PR, normal
RV function and less than moderate pulmonary artery Restriction for heavy exercise and athletics
dilatation. • Mild isotonic exercise with slow warm up and slow cool
down is usually recommended
Restriction for heavy exercise and athletics • Moderate to heavy isometric exercise like weight lifting
• Moderate or severe pulmonary stenosis should be avoided to prevent aortic dilatation/aneurysmal
• Severe pulmonary regurgitation with/without significant formation because of the associated aortopathy.
RV enlargement.
Tetralogy of Fallot (TOF)
Ebstein’s Anomaly
Exercise testing, baseline electrocardiogram and echo-
In Ebstein’s anomaly, the tricuspid valve abnormality and cardiography are essential for risk stratification of patients
its associated regurgitation leads to right heart enlargement with TOF, since exercise-induced QRS widening, more than
that may vary in severity, affecting clinical presentation 3 premature ventricular complexes in a row and ventricular
and exercise tolerance.42 If a patent foramen ovale is also arrhythmias, namely non-sustained ventricular tachycardia
present, there may be an increased right-to-left shunt due are prognostic signs for SCD.44,45
to abnormal diastology, causing cyanosis and decrease
exercise tolerance. The presence of an accessory pathway No restrictions
associated with Wolf-Parkinson-White (WPW) syndrome • Operated patients with good biventricular function, normal
may predispose to supraventricular tachycardia (SVT) right ventricular dimensions, mild pulmonary regurgitation,
during exercise. The progressive right atrial enlargement no significant right ventricular outflow tract obstruction
may contribute to atrial arrhythmias. Individuals at the (peak gradient less than 25 mm Hg), with absence of residual
severe end of the spectra of this defect may be at risk for or very small restrictive VSD on echocardiography, normal
SCD. QRS duration on electrocardiogram and are tolerating
isotonic exercises.
No restrictions
• Mild form of Ebstein’s anomaly with normal right Restrictions for heavy exercise and athletics
ventricular size and function • Operated patients with late repair leading to long-standing
• Absence of atrial or ventricular tachyarrhythmias pressure overload of RV (but with RVSP less than half
• Acyanotic. of systemic pressure), significant RV hypertrophy, RV
diastolic dysfunction
Restriction for heavy exercise and athletics • History of right ventriculotomy with annular patch
• Moderate tricuspid regurgitation repair (associated with risk of monomorphic ventricular
• No arrhythmias other than premature ventricular ectopy tachycardia originating from the RV scar).
• Post-tricuspid valve surgery with less than mild residual • Moderate PR
tricuspid regurgitation or right heart enlargement and no • Residual large VSD.
symptomatic atrial/ventricular arrhythmias.
Restrictions for moderate exercise
Restrictions for moderate exercise • Severe right outflow tract obstruction (risk of sudden
Severe form of Ebstein’s anomaly with significant right heart cardiac death is high when RVSP is between half to two-
enlargement and regurgitation. third of the systolic pressure) 821
http://vip.persianss.ir
10 • Severe PR operation depends on left ventricular function, patency of the
• Marked RV dilatation and decreased RV function coronary arteries and the pulmonary blood flow.50
• Inoperable severe PS or infundibular stenosis. Those with coronary ostial fibrosis or obstructive coronary
congEnital hEart disEasE in adults
ExErcisE and sports in adolEscEnts and adults with congEnital hEart disEasE
and congestion and difficulty in increasing preload that leads Syndromes
to low cardiac output. In addition, atrial arrhythmias have a
negative impact on exercise tolerance.54,55 Exercise recommendations for adolescents and adults with
Skeletal muscle function in Fontan patients is abnormal, specific syndromes such as Marfan or Down syndrome, are
which may have an impact in the reduced exercise tolerance discussed in their respective chapters.
encountered in these patients.56 Exercise training has beneficial
impacts on the skeletal muscle function in this population.57 YOGA AND TAI CHI CHUAN
Exercise testing should be performed before allowing
involvement in sports. Oxygen saturation should be tested The integrating mind-body relaxation techniques are
before and after exercise since intracardiac or intrapulmonary well known to have a positive effect on health outcomes,
shunting may reduce exercise tolerance. especially in patients with chronic diseases. More recent
studies have noted beneficial cardiovascular effects and
Restriction for Heavy Exercise and Athletics overall improvement in quality of life.62 By the nature of the
movements involved, it is possible for all people to perform
Patients with univentricular hearts who have had a Fontan certain Yoga and Tai Chi exercises despite the limitations
operation may have very good exercise tolerance and can imposed by other co-morbidities or age. Therefore, these
participate in low intensity sports if the: forms of exercises allow diverse application to people of all
• Systemic ventricular function is normal ages, cultures and infirmities.
• Oxygen saturation is normal. Yoga combines physical and breathing exercises that
have benefited people with many chronic health conditions.
Restrictions for Moderate Exercise Improved exercise tolerance and positive effect on levels of
inflammatory markers have been noted in patients with heart
• Moderate or severe ventricular dysfunction failure.63 Yoga respiratory training improves respiratory
• Arrhythmias function leading to an improvement of both the cardiac
• Reduced pulmonary functional capacity due to thoracic autonomic modulation and the sympathovagal balance
abnormalities (kyphoscoliosis). evaluated by heart rate variability.64 Pranayama, a yogic
exercise related to breathing, significantly reduces the indices
Eisenmenger physiology of ventricular repolarization dispersion in patients with
arrhythmia. Further studies are needed to assess its impact
Restrictions for moderate to heavy exercise and athletics on reducing the risk of malignant ventricular arrhythmias.65
Patients with Eisenmenger physiology have severe pulmonary Melville et al showed that yogic postures or meditation
vascular disease characterized by severe pulmonary performed in the office can acutely improve several
hypertension, due to reversal of shunt associated with an ASD, physiological and psychological markers of stress.66
VSD or PDA. Systemic vascular resistance may fall with Tai Chi is a low-impact, weight-bearing form of exercises
exercise and reduce the pulmonary venous return, leading characterized by gentle movements designed to dissipate
to exercise-induced syncope or SCD. Exercise tolerance is force throughout the body while the subject changes poses.
usually very restricted in this population.58 It involves well-coordinated sequences of both isometric
For risk stratification in the office, a six-minute walk test and isotonic segmental movements in the trunk and
is recommended with blood pressure, heart rhythm and pulse all extremities.67 Several studies have shown multiple
oximetry measurements taken before and after exercise. For cardiovascular benefits including improvements in blood
most patients, only mild isotonic exercise such as walking at pressure, arrhythmias and psychosocial well being.68,69 Like
a tolerable pace for short duration and very light weights (less yoga it appears to be safe and enjoyable for all age groups. For
than one lb/500 mg) with more repetitions to maintain muscle people with CHD, it could be a valuable alternative to both the
and bone strength are recommended. high and low intensity aerobic exercise regimens. Tai Chi is a
Exercise capacity and quality of life improves significantly group activity requiring only one supervising instructor for a
in iron-deficient patients with Einsenmenger syndrome, large number of people and is therefore cost efficient.70
after receiving three months of monitored iron replacement
therapy.59 Chronic nifedipine therapy has shown an increase in CONCLUSION
arterial oxygen saturation on exercise and improved maximal
exercise capacity in these patients.60 Bosentan, an endothelin Exercise and sports recommendations are designed to provide
receptor antagonist, has also shown an improvement in guidance to clinicians so that they can individualize medically 823
http://vip.persianss.ir
10
table 4 7. Mitchell JH, Haskell WL, Snell P, et al. Task Force 8. 36th
Bethesda Conference: Classification of sports. J Am Coll
Congenital heart defects and genetic disorders commonly
associated with sudden cardiac death during sports Cardiol. 2005;45:1364-7.
congEnital hEart disEasE in adults
ExErcisE and sports in adolEscEnts and adults with congEnital hEart disEasE
25. Maron BJ, Gohman TE, Kyle SB, et al. Clinical profile and Recommendations for the management of individuals with
spectrum of commotio cordis. JAMA. 2002;287:1142-6. acquired valvular heart diseases who are involved in leisure-
26. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. time physical activities or competitive sports. Eur J Cardiovasc
JAMA. 2002;287:1308-20. Prev Rehabil. 2008;15:95-103.
27. Kempny A, Dimopoulos K, Uebing A, et al. Reference 42. Trojnarska O, Szyszka A, Gwizdała A, et al. Adults with Ebstein’s
values for exercise limitations among adults with congenital anomaly–Cardiopulmonary exercise testing and BNP levels
heart disease. Relation to activities of daily life–single exercise capacity and BNP in adults with Ebstein’s anomaly. Int
centre experience and review of published data. Eur Heart J. J Cardiol. 2006;111:92-97. Epub 2005 Oct 19.
2012;33:1386-96. Epub 2011 Dec 23. 43. Luijendijk P, Bouma BJ, Vriend JW, et al.Usefulness of
28. Davis JA, Cecchin F., Jones, TK, et al. Major coronary artery exercise-induced hypertension as predictor of chronic
anomalies in a pediatric population: incidence and clinical hypertension in adults after operative therapy for aortic isthmic
importance. J Am Coll Cardiol. 2001;37:593-7. coarctation in childhood. Am J Cardiol. 2011;108:435-39.
29. Basso C, Maron BJ, Corrado D, et al. Clinical profile of Epub 2011 May 6.
congenital coronary artery anomalies with origin from the 44. Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for
wrong aortic sinus leading to sudden death in young competitive arrhythmia and sudden cardiac death late after repair of
athletes. J Am Coll Cardiol. 2000;35:1493-501. tetralogy of Fallot: a multicentre study. Lancet. 2000;356:
30. Maron BJ, Poliac L, Kaplan JA, et al. Blunt impact to the 975-81.
chest leading to sudden death from cardiac arrest during sports 45. van den Berg J, de Bie S, Meijboom FJ, et al. Changes
activities.N Engl J Med. 333 (1995). pp. 337-42 during exercise of ECG intervals related to increased risk for
31. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable ventricular arrhythmia in repaired tetralogy of Fallot and their
cardioverter-defibrillators for the prevention of sudden death
relationship to right ventricular size and function. Int J Cardiol.
in patients with hypertrophic cardiomyopathy. N Engl J Med,
2008;124:332-38. Epub 2007 Apr 11.
342.
46. Mathews RA, Fricker FJ, Beerman LB, et al. Exercise studies
32. Vermes E, Strohm O, Otmani A, et al. Impact of the revision
after the Mustard operation in transposition of the great arteries.
of arrhythmogenic right ventricular cardiomyopathy/dysplasia
Am J Cardiol. 1983;51:1526-9.
task force criteria on its prevalence by CMR criteria. JACC
47. Hesslein PS, Gutgesell HP, Gillette PC, et al. Exercise
Cardiovasc Imaging. 2011;4:282-7.
assessment of sinoatrial node function following the Mustard
33. Szymański P, Klisiewicz A, Hoffman P. ARVC/D task force
operation. Am Heart J. 1982;103:351-7.
imaging criteria: it is difficult to get along with the guidelines.
48. Budts W, Scheurwegs C, Stevens A, et al. The future of adult
JACC Cardiovasc Imaging. 2011;4:686.
34. Bluemke DA. ARVC: Imaging diagnosis is still in the eye of patients after Mustard or Senning repair for transposition of
the beholder. JACC Cardiovasc Imaging. 2011;4:288-91. the great arteries. Int J Cardiol. 2006;113:209-14. Epub 2006
35. Maron BJ, Douglas PS, Graham TP, et al. Task Force 1: Jan 10.
preparticipation screening and diagnosis of cardiovascular 49. Buys R, Van De Bruaene A, Budts W, et al. In adults with
disease in athletes. J Am Coll Cardiol. 2005;45:1322-6. atrial switch operation for transposition of the great arteries
36. Graham Jr TP, Bricker, JT, James FW, et al. Task Force 2: low physical activity relates to reduced exercise capacity
Congenital heart disease: 26th Betheda Conference. J Am Coll and decreased perceived physical functioning. Acta Cardiol.
Cardiol, 24.1994:867-73. 2012;67:49-57.
37. Graham Jr TP, Driscoll DJ, Gersony WM, eta al. Task Force 2: 50. Reybrouck T, Eyskens B, Mertens L, et al. Cardiorespiratory
Congenital heart disease. 36th Bethesda Conference. J Am Coll exercise function after the arterial switch operation for
Cardiol. 2005;45:1326-33. transposition of the great arteries. Eur Heart J. 2001; 22: 1052-
38. Waggoner AD, Barzilai B, Pérez JE. Saline contrast enhance- 9.
ment of tricuspid regurgitant jets detected by Doppler color 51. Hui L, Chau AK, Leung MP, et al. Assessment of left
flow imaging. Am J Cardiol. 1990;65:1368-71. ventricular function long term after arterial switch operation
39. Heidbüchel H, Panhuyzen-Goedkoop N, Corrado D, et for transposition of the great arteries by dobutamine stress
al. Study Group on Sports Cardiology of the European echocardiography. Heart. 2005;91:68-72.
Association for Cardiovascular Prevention and Rehabilitation. 52. Giardini A, Khambadkone S, Taylor A, et al. Effect of
Recommendations for participation in leisure-time physical abnormal pulmonary flow distribution on ventilatory efficiency
activity and competitive sports in patients with arrhythmias and and exercise capacity after arterial switch operation for
potentially arrhythmogenic conditions Part I: Supraventricular transposition of great arteries. Am J Cardiol. 2010;106:1023-
arrhythmias and pacemakers.Eur J Cardiovasc Prev Rehabil. 28. Epub 2010 Aug 17.
2006;13:475-84. 53. Fredriksen PM, Chen A, Veldtman G, et al. Exercise capacity
40. Heidbüchel H, Corrado D, Biffi A, et al. Recommendations in adult patients with congenitally corrected transposition of
for participation in leisure-time physical activity and the great arteries. Heart. 2001;85:191-5.
competitive sports of patients with arrhythmias and potentially 54. Ohuchi H. Cardiopulmonary response to exercise in patients
arrhythmogenic conditions. Part II: ventricular arrhythmias, with the Fontan circulation. Cardiol Young. 2005;15:39-44.
825
http://vip.persianss.ir
10 55. Ohuchi H, Hamamichi Y, Hayashi T, et al. Post-exercise heart
rate, blood pressure and oxygen uptake dynamics in pediatric
heart failure. J Card Fail. 2008;14:407-13. Epub 2008
May 27.
patients with Fontan circulation Comparison with patients after 64. Santaella DF, Devesa CR, Rojo MR, et al. Yoga respiratory
congEnital hEart disEasE in adults
right ventricular outflow tract reconstruction. Int J Cardiol. training improves respiratory function and cardiac
2005;101:129-36. sympathovagal balance in elderly subjects: a randomised
56. Brassard P, Poirier P, Martin J, et al. Impact of exercise training controlled trial. BMJ Open. 2011;1:e000085.
on muscle function and ergoreflex in Fontan patients: a pilot 65. Dabhade AM, Pawar BH, Ghunage MS, et al. Effect of
study. Int J Cardiol. 2006;107:85-94. Epub 2005 Jul 19. pranayama (breathing exercise) on arrhythmias in the human
57. Brassard P, Bédard E, Jobin J, et al. Exercise capacity and heart. Explore (NY). 2012;8:12-5.
impact of exercise training in patients after a Fontan procedure: 66. Melville GW, Chang D, Colagiuri B, et al. Fifteen minutes
a review.Can J Cardiol. 2006;22:489-95. Review. of chair-based yoga postures or guided meditation performed
58. Müller J, Hess J, Hager A. Exercise performance and quality in the office can elicit a relaxation response. Evid Based Com-
of life is more impaired in Eisenmenger syndrome than in plement Alternat Med. 2012;2012:501986. Epub 2012 Jan 16.
complex cyanotic congenital heart disease with pulmonary 67. Caminiti G, Volterrani M, Marazzi G, et al. Tai chi enhances
stenosis. Int J Cardiol. 2011;150:177-81. Epub 2010 May 1. the effects of endurance training in the rehabilitation of
59. Tay EL, Peset A, Papaphylactou M, et al. Replacement therapy elderly patients with chronic heart failure. Rehabil Res Pract.
for iron deficiency improves exercise capacity and quality of 2011;2011:761958. Epub 2010 Sep 13.
life in patients with cyanotic congenital heart disease and/or 68. Cheng TO. Tai Chi: the Chinese ancient wisdom of an ideal
the Eisenmenger syndrome. Int J Cardiol. 2011;151:307-12. exercise for cardiac patients. Int J Cardiol. 2007;117:293-95.
Epub 2010 Jul 1. Epub 2006 Aug 9. Review.
60. Wong CK, Yeung DW, Lau CP, et al. Improvement of exercise 69. Yeh GY, Wood MJ, Lorell BH, et al. Effects of Tai Chi mind-body
capacity after nifedipine in patients with Eisenmenger movement therapy on functional status and exercise capacity in
syndrome complicating ventricular septal defect. Clin Cardiol. patients with chronic heart failure: a randomized controlled trial.
1991;14:957-61. American Journal of Medicine. 2004;117:541-8.
61. Fine N, Dias B, Shoemaker G, et al. Endothelin receptor 70. Barrow DE, Bedford A, Ives G, et al. An evaluation of the
antagonist therapy in congenital heart disease with shunt- effects of Tai Chi Chuan and Chi Kung training in patients with
associated pulmonary arterial hypertension: a qualitative symptomatic heart failure: a randomised controlled pilot study.
systematic review. Can J Cardiol. 2009;25:e63-8. Postgraduate Medical Journal. 2007;83:717-21.
62. Brown DR, Wang Y, Ward A, et al. Chronic psychological 71. Balady GJ, Ades PA, Comoss P, et al. Core components of
effects of exercise and exercise plus cognitive strategies. cardiac rehabilitation/secondary prevention programs: a
Medicine and Science in Sports and Exercise. 1995;27:765-75. statement for healthcare professionals from the American Heart
63. Pullen PR, Nagamia SH, Mehta PK, et al. Effects of yoga on Association and the American Association of Cardiovascular
inflammation and exercise capacity in patients with chronic and Pulmonary Rehabilitation. Circulation. 2000;102:1069-73.
826
Psychosocial Challenges and
C hapter
http://vip.persianss.ir
10 appearance. For the adolescent with CHD, loss may mean On the opposite end of the spectrum, some patients were
never having the opportunity to participate in team sports or told that they had ‘corrective’ surgery and that they were
other physical or social activities. For an adult woman with ‘cured’. I was one of those lucky ‘miracle babies’ and I
Congenital Heart Disease in Adults
CHD, it sometimes means not being able to have a child remember hearing this repeatedly as a child and finally let
of her own (biological and/or adopted). There is often an my ‘emotional guard down’ (after hearing ‘don’t worry, you
enormous sense of grief for these along with other losses, worry too much’ from both physicians and family) only to
which must be worked through in order to move on and end up with multiple cardiac problems as a young adult*.
carve out a meaningful life for oneself. Unfortunately, many CHD patients, after years of clinical
This grief is sometimes complicated by society’s reaction to stability experience deterioration in their health and ability to
these feelings. One example of this is the common belief that function. These patients often feel ‘angry and betrayed by their
the longer one lives with a loss, the easier it is to overcome, i.e. hearts, health, physicians and families’ because no one told
“Since I have lived with this my whole life, I should be over them that they may have to face cardiac difficulties again.5 As
it by now”. Some patients actually have disclosed feelings of a result, shock, anger, denial and fright are different emotional
guilt regarding their intermittent or delayed feelings of loss. reactions that many of these patients can experience. Often
However, for many CHD patients, it is not developmentally the return of cardiac symptoms can propel the individual to
possible for them to realize the full extent of their illness until recount previous hospitalizations which may only contribute
they reach adulthood. to their anxiety, fear and uncertainty about their future.
Struggles with body image and the perception of being Another theme occasionally expressed by patients with
different were mentioned in one study as being significant CHD is awareness that the human heart holds strong symbolic
issues in this patient population.4 Scarring, cyanosis and meaning. For many it signifies emotion, the center of life, love
physical restrictions are just some of the issues many of and the human spirit. For some, this resonates beyond their
these patients must learn to cope with on a daily basis. For a physical cardiac lesion and symptomatology; when one has a
teen struggling to ‘fit in’ with his/her peers, this can often be ‘broken heart’ this in of itself can have tremendous impact on
extremely difficult as peer relationships are such an important one’s psyche. This concept was expressed so well by Fischer
part of individuation process. For adults, this theme is often and Cleveland ‘by producing a rhythm felt throughout the
revisited when deciding how and what to tell a romantic body, the heart plays a fundamental role in the individual’s
partner or employer regarding their CHD and then dealing image of self’.4
with potential negative reactions.
Academic performance and employment choices are also Quality of Life
important issues facing by patients. For some, occupational
success is hampered by lapses in school or work due to their Quality of life “reflects a patient’s life satisfaction and ability to
CHD. Health insurance and the financial ability to support function in a variety of life domains including physical, social,
oneself is a consideration for the young adult transitioning emotional and work-related”.7 A study conducted by Moons
from their parents care. Many of the studies suggest that and colleagues defined quality of life as “the degree of overall
moving into a state of independence can be challenging for life satisfaction that is positively or negatively influenced by
some CHD patients. One study found that 83 percent of individuals’ perception of certain aspects of life important to
their subjects chose to stay close to their family home and them, including matters both related and unrelated to health”.8
medical care.5 Another study found that “among patients with Despite the higher rates of psychological distress and the
congenital heart disease there were significantly more of those psychosocial issues described above, some of the research
who had developed a dependent life style, living with their has shown that CHD patients are thriving in many ways and
parents without a marital or quasi-marital relationship”.6 actually report having a better quality of life than their non-
Verstappen articulately describes how the early messages CHD counterparts.9 Much of the research has shown that this
some CHD patients are given can greatly affect their overall group of individuals perseveres. One study had found that in
perspective with regards to their illness and how they live terms of academic achievement and occupational status “these
their lives.3 One message that was given to some was that they respondents seem clearly beyond what one would expect in a
would not live long. As one can imagine, medically centered normal adult population” and that by various criteria, these
anxiety, fear of death and apprehension regarding important patients seemed ‘successful.’10
decision making are all potential emotional consequences of
such a belief. Many of these same patients, now adults, are Role of the Provider Caring for Patients with
alive and wondering how to play ‘catch up’ in terms of their life Congenital Heart Disease
choices (or lack of). Some may still be living with their parents
while others may wish they had invested in certain academic or As a provider, the following measures have shown positive
career choices. Some may find themselves alone as they were outcomes in our practice**. First of all, communication is
828 never able to build a long-term, intimate relationship. the key. We need to stop, look and understand. One needs to
understand, acknowledge the special needs, then approach CHD especially in those with complex CHD and/or cyanotic 58
the individuals with CHD as well as their families in a kind CHD. We have seen many young girls and boys express
and sensitive manner. Knowing their lifelong struggles, their distress over the teasing that goes on in schools because they
Psychosocial Challenges and Psychiatric Issues while Growing Up with Congenital Heart Disease
challenges and limitations should lead us to individualize have kyphoscoliois, cyanosis, clubbing or visible scars.
management for each person. The clinic and the hospital It is important to encourage ‘positive thinking’ and make
environment should to be warm, friendly and resourceful. the patient and families aware of ‘realistic expectations’. The
When faced with a medical or surgical emergency, it is door should be left open with regards to questions relating to
common for the patient and their family to feel overwhelmed long-term outcomes and possibilities such as “What does the
even if they are health care professionals. At this time of need, future hold for me? The fields of medicine and surgery are
there should be an established support system to help them constantly in evolution and therefore the recommendations
navigate physically, emotionally, mentally and spiritually also change over time.
through the medical system with their difficulties. The Clinical I have several patients who never got married or had
Social Worker and the Clinical Nurse Specialist (Registered families because they were told several decades ago that it
Nurse or Advanced Nurse Practitioner) who are involved in would ‘not be feasible for them’ to do so. However, the
caring for people with chronic disabilities (especially CHD) outcomes are far more positive if the health care provider
are most resourceful. The families should have their contact informs them of their ‘current’ abilities and limitations. They
information in order to reach them promptly. should be given hope by encouraging them to follow-up and
For routine care, the physicians and the Clinical Nurse stay up-to-date with the changing paradigms. Guiding people
Specialist should make sure that there is a sound system to as to how they can experience the best possible outcome in
ensure follow-up appointments, discuss test results, answer every situation heals them from despair over time. Reminding
questions/concerns for the patients and their families. ourselves that we mentally, psychologically and spiritually
Prescriptions should be filled in an efficient and timely fashion. make our own choices is critical to our existence. The World
These measures can help reduce anxiety and lapses in care. Health Organization (WHO) defines health as a state of
We need to have genuine respect for our patients and allow complete physical, mental, social well-being and not merely
them to be ‘active’ participants in their health care. We need the absence of disease or infirmity. For a complete sense of
to ‘empower’ them with the knowledge and understanding well-being, all the aspects of health need to be addressed.
of the routine care relating to their condition. Knowledge is As providers, our task is to provide the best information in
powerful and sharing information is even more powerful. order for the individuals with CHD and their families to make
Health education classes, handouts and online resources help the best decisions from time to time. Facilitating transition
those who are more receptive and the most effective moment through stages of life, especially from childhood to adulthood
for a health care provider to share the key information is at is vital for the continuity of care. The chapter on Transitional
the clinic visit or during the hospitalization. These measures Care in Congenital Heart Disease (Chapter 53) deals with this
promote compliance with preventive care, follow-ups and matter in more detail.
medical/surgical treatments. Counseling for personal needs, advice regarding intimacy,
Denial is noted in many individuals with CHD from early pregnancy and contraception are often ignored aspects of
in life. This may come from parents, the children themselves medical care. Both men and women often have fears of passing
or the health care providers (especially physicians). Denial their congenital heart condition to their children or having them
and minimization can be both adaptive and maladaptive. suffer like they did. They are also worried about living long
Although, denial may help ‘normalize’ functioning with enough to raise a child. Patients are usually too embarrassed
regards to survival (such as with education and employment), to bring up this issue. Many general practitioners are reluctant
it can camouflage serious emotional problems leading to to prescribe oral contraceptives to women with underlying
high rates of undiagnosed or untreated mood and anxiety heart disease.4 On the other side of the spectrum, women with
disorders seen in this population. It has been observed that cyanotic congenital heart disease may face fertility issues and
very rarely patients have requested referrals and been referred are also at higher risk for carrying a pregnancy should they
to a psychiatrist/psychologist. Their happy appearance may conceive. For many women not being able to bear children
cover feelings of fears of decline, premature death, loneliness, because of their cardiovascular condition, can be a devastating
isolation, anxiety and depression. These feelings can be blow to their sense of identity and self worth.5 The Clinical
disabling especially in those who are single, unemployed and Nurse Specialist and the Clinical Social Worker are often
isolated.5 most tactful in laying the groundwork by gently addressing
One of the most common phrases that I hear from my these issues in a one-to-one session with the patients who are
patients is “I want to be normal”. The definition of ‘normal’ is generally too shy or embarrassed to bring these matters up in
relative. It depends on the person and on his or her cultural and front of their families. These patients can then be directed to
environmental expectations. Many studies have shown that their physicians to address the technical aspects in dealing with
feeling ‘different’ is a common experience among patients with these issues. 829
http://vip.persianss.ir
10 Informative discussions on these issues can help allay their when turned around. A positive mindset and optimism can
fears and concerns. Some of these guidelines are discussed help immensely. Most limitations are the ones that we impose
in more detail in the chapter on Pregnancy, Contraception on ourselves.
Congenital Heart Disease in Adults
and Gynecological Issues in Women with Congenital Heart Work is usually highly valued among most people with
Disease (Chapter 56) A significant number of women with CHD and they usually show amazing resilience in continuing
CHD are able to have pregnancies, some choose adoption, to be productive despite their physical limitations. Most of
while others may have accidental pregnancies that they choose them display persistence, perseverance, a tremendous amount
to terminate. of patience in achieving their lifetime dreams and goals. We
The families of the individuals with CHD also need a lot of can see the proof of this in our day to day practice where
support since they too suffer from many psychosocial issues. many of our patients grew up and followed their dreams to
Many mothers feel responsible for their child’s illness and project become emotionally, socially and economically successful.
onto the sick heart all their suffering and sorrow. This may lead Some chose careers in the health care profession and are
to activation of unconscious aggressive feelings in the parents very sensitive to the needs of others. Many rose above
and overprotective behavior towards the child. The family their physical limitations to participate in exercise and
may first react to the diagnosis with shock, discouragement sports beyond expectations. Some were triumphant in the
and depression. This may be followed by a phase of struggle Special Olympics and other physically challenging sports.
against the medical illness or they may end up in denial of the Most survivors with CHD are extraordinarily courageous,
illness. Chronic diseases often lead to a reorganization of the usually determined to work, contribute to society and be as
family system around the illness. Siblings may also be affected ‘normal’ as possible.1 Although, studies have shown that their
and are at increased risk for psychopathological disorders such level of education exceeded the national average, there are
as behavioral and/or psychosomatic issues. Group meetings many who consider themselves disabled and do not pursue
with parents allow involvement of the parents in the treatment higher education or vocational training to gain meaningful
plans. They help them overcome these issues by discussing employment. Career and vocational counseling should be an
their hopes, fears and anxieties.11 Not to be ignored are the integral part of any CHD program.12 The goal is to assist the
family stressors relating to an increased strain and drain on the patients in selecting a career corresponding to their special
family financial situation, from health care expenses. In the needs or clinical limitations, while serving their personal
unfortunate event of a death of the child, adolescent or adult interests and aspirations.
with CHD, family support and bereavement services should be It is important to feel good deep inside and therefore the
made readily available. ‘spirit’ cannot be ignored. The most important goal is to have
Patient driven support groups, national and international love, peace, harmony and balance in life for that is what we all
association programs play an important role for most of strive towards. Encouraging empowerment, offering support
our internet-savvy patients. The Adult Congenital Heart and encouraging realistic, yet positive thinking can assist
Association is very active in its efforts with patient advocacy, patients in having the courage to work towards their goals.
in spreading knowledge, promoting research, offering social
networks and peer support (www.achaheart.org). The National PSYCHIATRIC ISSUES
Marfan Foundation and its local chapters also promote
patient education, support through their websites, regional
and national conferences as well as other forums (www.nmf.
Introduction
org). The International Society for Adults with Congenital It has been found in a number of studies that this patient
Heart Defects (www.isachd.org) offers many resources to population tends to have a higher incidence of mental health
professionals and the public. A listing of international adult issues than the general public. Brandhagen found that the
congenital heart disease (ACHD) groups is available at www. “General psychologic development in adults with congenital
worldcongenitalheart.org. Individual clinics/centers can heart disease differed from that in a normal population.”10
provide information regarding local resources, support groups To substantiate, one study found that among CHD patients
to the patients/families to meet their personal and cultural “who had been assumed to be ‘well-adjusted’, 36.4 percent
needs more adequately. People with CHD have a unique were experiencing a diagnosable psychiatric disorder,
impact on their healthcare and policies when they speak with anxiety or depressive symptoms being prominent”.13
directly of their own experiences.3 Another found that “Fifty percent of interviewed patients met
Appropriately educating complex CHD survivors requires diagnostic criteria for at least one lifetime mood or anxiety
honesty and humility on the part of the providers. Promoting disorder”,14 Finally another study found that approximately
the connection between the ‘BODY, MIND AND SPIRIT’ 79 percent of the CHD patients interviewed presented either
ultimately helps them the most in their lifelong journey. Both with a diagnosable psychiatric disorder of major depression,
the patient and the provider need to acknowledge the power panic disorder or were found to be suffering from “frequently
830 of the ‘Mind over Matter’. For some, adversity can be a gift endorsed clusters of psychiatric symptoms not meeting criteria
for full disorder (post-traumatic stress disorder, dysthymia, of cardiac lesion and the degree of psychological distress10 58
adjustment disorder with depressed mood and/or anxious but yet another found ‘significant correlations.’13 Finally,
mood, either currently or in the past)”.5 yet another study found that a person’s “social adjustment
Psychosocial Challenges and Psychiatric Issues while Growing Up with Congenital Heart Disease
One psychiatric diagnosis which is not often mentioned and patient-perceived health status are more predictive of
in the literature is post-traumatic stress disorder (PTSD). depression and anxiety than medical variables”.14
This is despite the fact that ‘childhood illness qualifies as a Could this increase of psychiatric conditions be connected
traumatic stressor’ in the diagnosis of PTSD.15 In one study, it to the entry to adulthood? All of the tasks that this transition
was found that approximately 29 percent of adolescents who requires (choosing and maintaining employment, supporting
had undergone cardiac surgery as children were diagnosed oneself financially, maintaining an intimate relationship) could
with ‘full post-traumatic stress disorder (PTSD) likely’.16 It simply be a reminder of one’s differences and limitations. This
is our recommendation that further research into this topic be would be especially true for those who were never ‘prepared’
conducted as there is “preliminary evidence that PTSD may for entering adulthood. One could also say that the experience
be associated with non-adherence with medication and an of living with a life threatening condition, especially during
increased risk of clinical adverse events”.17 one’s formative years, is in of itself enough to contribute to
It has consistently been found that mental health treatment this increased prevalence. After living with repeated traumatic
for these patients is greatly lacking. Kovacs stated that events, the underlying fear of ‘it’ happening again often stays
“approximately, 70 percent of the patients who met diagnostic with the individual. The effect this has on a person can vary
criteria at the time of study participation were not engaged greatly and can manifest on so many different emotional and
in mental health treatment”.14 Furthermore, none of the psychological levels.
patients with diagnosable psychiatric disorders or clusters of Another possible explanation for this increased prevalence
psychiatric symptoms in both the Bromberg13 and Horner5 of psychiatric presentation is that perhaps there is a more
studies were in mental health treatment of any kind. biological involvement due to lower blood oxygen levels,
The need for improved identification and treatment of limitations in physical activity, and due to the effect of
psychological disorders in this patient population could not be their cardiac medications.13 There is also an association of
more clear or convincing. Yet, as illustrated above, this very psychiatric conditions with other cardiovascular diseases such
important aspect of their care is greatly lacking. This is despite as coronary artery disease and heart failure. A higher incidence
the recommendation of the 32nd Bethesda Conference (“Care of clinical depression and anxiety is noted in patients after
of the Adult with Congenital Heart Disease”) which stated in myocardial infarction, coronary artery bypass surgery and
the summary document: “The emotional health of adults with with chronic heart failure. It is believed to be due to lower
congenital heart disease should be a priority in the overall care blood oxygen levels during a myocardial infarction and the
of this patient population. Appropriate screening and referral cardiac surgery. It is also related to the life style changes
sources for treatment should be available at all regional ACHD people have to make after having a heart attack or following
centers”.18 Additionally, the Task Force on the Management of a heart surgery. Psychiatric conditions worsen the prognosis
Grown Up Congenital Heart Disease of the European Society of heart disease and vice versa, heart diseases have a major
of Cardiology for grown-ups with congenital heart disease adverse impact on mental health and psychiatric issues.21
stated “(Practitioners) must be prepared to help patients and Regardless of what the reasons for the connection to CHD
their families with numerous psychosocial issues and work on and psychiatric prevalence are, as health care professionals
a multidisciplinary basis to provide psychological support.”19 we must examine why CHD patients, for the most part, are
There is some research on the connection between CHD not receiving the mental health treatment that they need. This
and psychiatric prevalence. One study began with a hypothesis brings light to the issue of stigma, which unfortunately prevails
that “improvements in medical care would result in more in many cultures when it comes to the acknowledgement of
favorable behavioral and emotional outcomes for children and mental health conditions and the need for treatment.
adolescents with CHD treated recently”. Could the medical
care patients received in the infancy of CHD treatment have had Stigma
enough of an effect to cause an increased rate of psychological
symptomatology? This group compared patients operated on What is Stigma?
before 1980 with a group of patients operated on 10 to 15
years later. They found that “despite evident improvements in Stigma can be defined as a sign of disgrace or discredit, which
diagnostic and surgical techniques and medical treatment of sets a person apart from other. According to Goffman, the
CHD over the past decades, virtually no changes were found difference between a ‘normal’ and stigmatized person is a
in levels of problem behavior”.20 Another potential contributor question of perspective not reality. There is also a ‘courtesy
that has been examined is the possible connection between stigma’ where family members feel embarrassed or ashamed
medical severity and degree of psychological stress. One study of the illness of their loved ones, whether it is an emotional or
found that there was no correlation found between the severity a physical condition.22 831
http://vip.persianss.ir
10 How do We Deal with Stigma? not enough. There continue to be many obstacles to addressing
the psychological needs of these patients. A lack of funding
Education is the first and most important factor in fighting and a deficiency of psychosocial awareness on the part of
Congenital Heart Disease in Adults
stigma. It helps with the ‘fear of the unknown’ and takes down CHD faculty, as well as patients and families are two areas
the walls that people create to psychologically and at times to of concern. Additionally, our experience shows that there is
physically protect themselves. Education should be provided a fear on the part of some patients of not being understood
to the young patients at a level that they can understand by (mental health) treatment providers. Many patients have
clearly. As more understanding grows, patients become less described the frustration of having to explain their medical
embarrassed about their condition and will hopefully begin to history repeatedly to mental health care providers only
feel less ‘different’. Providing psycho-education can also help to receive a variety of unhelpful responses ranging from
patients and family members spread pertinent information to astonishment to pity. Perhaps, this is why it was found that
the people in their lives and circles. Eliminating the fear of only 35 percent of the CHD patients in one study were found
the unknown relating to a medical condition can be helpful. to be interested in receiving peer support.23
The stigma attached to illnesses like HIV/AIDS has been
successfully challenged by educating people more about Management of Children Growing Up
the facts versus the myths. Educational programs, media, with Chronic Disabilities
and support groups for families can assist in promoting
such efforts. Many health conditions receive positive public Rapprochement is a part of a phase of development in toddlers
attention (therefore reducing stigma) when high profile people postulated by Margaret Mahler.25,26 In this sub-phase, a toddler
or celebrities openly discuss their personal medical conditions. practices being independent and wants to explore ‘the world’.
The child realizes that his physical mobility demonstrates
Role of Mental Health Services psychic separateness from his mother. The child has a fear of
mother (primary caregiver) not being there when she is needed.
Mental Health Services can provide emotional support, This phase can be disturbed in children who are challenged
coping strategies and the opportunity to explore one’s with medical illnesses such as CHD and who are undergoing
thinking for distortions that may adversely affect life goals a medical or surgical procedure. His/her experience with
and relationships. Coping strategies which may have their CHD may cause a child to become clingy to the parents
been appropriate in childhood may no longer serve well in and issues of separation anxiety can arise. It is believed that
adulthood. Distortions of thinking may cause unwarranted adolescents go through the same phase when they want to
sensitivity to rejection, social isolation or deferral of fulfilling practice their independence. It is also a time in their life when
activities. existential questions are raised in the mind. The questions
An important issue in making a referral to mental health such as “Who am I?”, “Why am I in this world?” and “Who
services is the level of comfort and knowledge on the part do I belong to (in the psychological sense)?” These are some
of the health care provider and the patient in addressing of the things that make this phase of life so challenging. It is
psychiatric issues. Discussion of the physiologic processes when the normal developmental challenges of independence
(the role of Serotonin, for example) involved in anxiety or are coupled with the added stressor of a child’s heart disease
depression symptoms may help reduce stigma for the patient that significant psychological issues can arise.
in need of mental health services. This may be why it is common to see some children
Our experience has shown that although many CHD become increasingly non-compliant with treatment during
patients do want mental health treatment, denial, lack of adolescence. Other factors that may affect non-compliance
acknowledging the need, the stigmata and paucity of access are the general attitude of invincibility (in adolescence) and
to care may make it challenging for people based upon their denial used as a way of coping with their illness. Parents
demographics. This is substantiated by a study which found and providers can help by acknowledging and validating
that 51 percent of patients “indicated a high interest in at the adolescent’s health situation, feelings or struggles. They
least one of the seven defined focus areas of psychological can offer psychological education, unconditional love and
treatment”.23 Unfortunately, however, according to Horner, acceptance. Partnering with them, instead of telling them what
“CHD patients in adulthood, as in their childhood, often to do has more chances of success.
suffered silently and worried alone.”5 Denial has been cited as
a common psychological defense in this patient population.5 Management of Depression and Anxiety disorders
The fact that many CHD patients in need are not receiving
treatment is especially concerning since there is “existing The treatment for depression and anxiety should be three-fold:
evidence that social support and emotional expression may be biologic, psychotherapy and lifestyle changes.27 The biologic
associated with better medical outcome” (cancer patients).24 treatments are discussed in the section “Pharmacological
832 Although, many ACHD centers do offer some form of interventions in patients with cardiovascular disease”.
mental health services, the findings above indicate that it is Psychotherapy can help in understanding one's patterns of
thinking, how a person copes with situations and how a chronic failure due to coronary artery disease.28-31 In addition, the 58
medical condition has affected his/her social, occupational or positive impact of exercise training in patients with depression
educational life. Cognitive behavior therapy techniques can and heart failure due to coronary artery disease should be
Psychosocial Challenges and Psychiatric Issues while Growing Up with Congenital Heart Disease
be used in helping patients focus on “seeing the glass half- extrapolated to other cardiac patients (including those with
full rather than half-empty”. Lifestyle changes relating to congenital heart disease).32
‘Healthy Living’ by eating healthy and incorporating exercise Effexor (Venlafaxine) is an antidepressant and anti-
in their daily routine are advocated. Stress management with anxiety medication that is considered to be a serotonin and
meditation, activities that bring peace, harmony such as music, norepinephrine reuptake inhibitor (SNRI). It can cause an
dancing, gardening and yoga should be a part of everyone’s life. elevation in blood pressure and should be used cautiously with
Patients should also be encouraged to think about their proper monitoring. Benzodiazepines such as lorazepam and
priorities in life and how to take control of the direction of clonazepam are good medications in reducing acute anxiety.
their lives in a realistic way. Finding the enjoyment in the Clinicians have to be very careful in using any psychotropic
little things such as a walk in the park, a stroll by the beach medications that may increase the heart rate, blood pressure
or enjoying a cup of tea over a conversation with a friend can or prolong the corrected QT interval (QTc). For example,
also help in feeling fulfilled in one’s life. We think that it is also stimulant medications commonly used to treat attention-
important for CHD patients to define themselves not by their deficit hyperactivity disorder (ADHD) or lethargy related to
illness but instead as individuals with ideas, interests, goals depression, can increase heart rate and blood pressure. These
and dreams. drugs have potential side-effects including cardiac arrhythmias.
Their use may be contraindicated in patients with CHD who
An Approach to Post-traumatic Stress Disorder have significant electrophysiological issues. Therefore, a
baseline electrocardiogram and a cardiology consultation are
The best approach to post-traumatic stress disorder (PTSD) is needed before prescribing these medications. Because the
to minimize the emotional trauma during the treatment. The benzodiazepines can be habit-forming and may cause memory
health care provider can help by preparing the patient with problems, their use should be for short-term only especially
education about their illness or the procedure that they are during acute phases, until the long-term medications such as
about to have. When it is possible, and especially in the case of SSRIs or SNRIs start working. Most antipsychotic medications
children, being close to a loved one until it is time to go under used to treat psychotic disorders such as schizophrenia or mood
anesthesia is very supportive. Processing the traumatic events disorders such as bipolar disorders can prolong the QTc interval
as early as possible can aid in any situation, so the same would (Figure 1). The worst offenders are Ziprasodone (Geodon) and
be true when dealing with a patient’s medical trauma. After Thioridazine (Mellaril). Weight gain, elevated triglycerides and
the procedure, guiding the patient back to their normal life as cholesterol are potential side-effects of this class of medication.
soon as possible also helps in faster recovery, both emotionally Close monitoring for potential side-effects should be provided.
and physically. Nature created human beings with the ‘flight or The tricyclic antidepressants (TCAs) should be used
fight response’, so that when a danger arises, initially certain with caution. A baseline electrocardiogram should be
hormones get pumped into the blood to allow us to either obtained before starting this class of medications. Follow-up
fight it or get out of it. After a short period of time, the body’s electrocardiograms should be checked annually or if there are
response diminishes and everything goes back to the baseline. any cardiac symptoms. In children, Imipramine in low doses
The challenge in patients with chronic illnesses or stress- can be effective for nocturnal bed wetting and desipramine
related disorders is that their bodies and emotions are in that has shown efficacy in treating attention-deficit hyperactivity
state of ‘flight or fight response’ all the time. This takes a toll disorder (ADHD).33,34
on them, unless they are able to seek help in order to recognize Unfortunately, there are case reports of sudden death
these patterns and learn new healthy coping skills. associated with the use of TCAs. Nortriptyline is used to treat
obsessive compulsive disorder (OCD) in both children and
Pharmacological Interventions in Patients adults. TCAs are also used for controlling severe neurological
with Cardiovascular Disease pain and migraine. With the advent of newer antidepressants,
the use of TCAs is now becoming limited. These agents are
Along with counseling, supportive care, the pharmacological still used in treatment of refractory depression.
interventions play a major role in management of depression,
anxiety disorders and other mental conditions in patients with Drug-drug Interactions
CHD as well as in those with other cardiovascular diseases.
Among biologic therapies, the selective serotonin reuptake Selective serotonin reuptake inhibitors (SSRIs) are widely
inhibitors (SSRI) such as fluoxetine, sertraline, paroxetine, used and since most patients are taking multiple medications,
citalopram, have shown to be very effective in treating both it is very important to be aware of drug-drug interactions.
depression and anxiety. There is a rising interest in the use Like many other drugs, SSRI's are metabolized by 833
of SSRIs in cardiac patients, especially in those with heart cytochrome P450 system. Many drugs may increase or
http://vip.persianss.ir
10
Congenital Heart Disease in Adults
Figure 1: Electrocardiogram showing long corrected long QT interval (QTc). The QT interval
should be corrected to age, gender and heart rate
Table 1
Medications and agents that may increase levels or toxicity when used with selective serotonin reuptake inhibitors (SSRIs)
Psychosocial Challenges and Psychiatric Issues while Growing Up with Congenital Heart Disease
8. Moons P, Marquet K, Budts W, et al. Validity, reliability and
Integrate mental health care providers into the CHD medical
responsiveness of the “Schedule for the Evaluation of Individual
team and also utilize them as a community referral resource.
Quality of Life-Direct Weighting” (SEIQoL-DW) in congenital
Develop outreach strategies designed to identify mental health heart disease. Health Qual Life Outcomes. 2004;2:27.
care providers (clinical social workers and psychologists) and 9. Moons P, Van Deyk K, De Bleser L, et al. Quality of life and
ideally refer to those who are specially trained in working with health status in adults with congenital heart disease: a direct
patients with CHD. comparison with healthy counterparts. Eur J Cardiovasc Prev
Establish a plan to develop and test ‘tools for screening of Rehabil. 2006;13:407-13.
psychosocial problems’ in this population.18 10. Brandhagen DJ, Feldt RH, Williams DE. Long-term
Provide psychological education to the faculty (at the psychologic implications of congenital heart disease: a 25-year
ACHD and Pediatric Centers), patients and family members follow-up. Mayo Clin Proc. 1991;66:474-9.
regarding identification, treatment and recommendations for 11. Masi G, Brovedani P. Adolescents with congenital heart
psychosocial/psychiatric issues. disease: psychopathological implications. Adolescence. 1999;
34(133):185-91.
Pediatric Centers should offer transitional support to assist 12. Simko LC, McGinnis KA. Quality of life experienced by adults
adolescents with the move to adult care. with congenital heart disease. AACN Clin Issues. 2003;14: 42-
Offer patient support groups and ‘peer to peer’ relationships 53.
locally. 13. Bromberg JI, Beasley PJ, D’Angelo EJ, et al. Depression and
Provide crisis intervention and psychotherapy (talk therapy) anxiety in adults with congenital heart disease: a pilot study.
to patients when indicated. Heart Lung. 2003;32:105-10.
14. Kovacs AH, Saidi AS, Kuhl EA, et al. Depression and anxiety
Short-term psychotherapy administered through the ACHD
in adult congenital heart disease: predictors and prevalence. Int
centers.
J Cardiol. 2009;137:158-64. Epub 2008 Aug 15.
Long-term counseling referred out to appropriate affiliated 15. Manne S. Commentary: Adopting [corrected] a broad per-
mental health programs and community resources. spective on post traumatic stress disorders, childhood medical
Inpatient counseling provided following a cardiac episode or illness and injury. J Pediatr Psychol. 2009;34:22-6. Epub 2008
prior to cardiac procedures and surgery. Apr 25. Erratum in: J Pediatr Psychol. 2009;34:338.
16. Toren P, Horesh N. Psychiatric morbidity in adolescents
operated in childhood for congenital cyanotic heart disease. J
Paediatr Child Health. 2007;43:662-6.
life more meaningful. As providers, we should encourage 17. Spindler H, Pedersen SS. Posttraumatic stress disorder in the
wake of heart disease: prevalence, risk factors, and future
the patients to feel more empowered when dealing with their
research directions. Psychosom Med. 2005;67:715-23.
health conditions.
18. Foster E, Graham TP Jr, Driscoll DJ, et al. Task force 2: special
health care needs of adults with congenital heart disease. J Am
To keep the body in good health is a duty, otherwise we shall Coll Cardiol. 2001;37:1176-83.
not be able to keep our mind strong and clear. 19. Baumgartner H, Bonhoeffer P, De Groot NM, et al. Task Force
—Gautama the Buddha, 563 BC on the Management of Grown-up Congenital Heart Disease of
the European Society of Cardiology (ESC). ESC Guidelines
REFERENCES for the management of grown-up congenital heart disease
(new version 2010). Eur Heart J. 2010;31:2915-57. Epub 2010
1. Warnes CA. The adult with congenital heart disease: born to be Aug 27.
bad? J Am Coll Cardiol. National Heart Lung. 2005;46:1-8. 20. Spijkerboer AW, Utens EM, Bogers AJ, et al. A historical
2. What are Congenital Heart Defects? National Heart, Lung comparison of long-term behavioral and emotional outcomes
and Blood Institute, Diseases and Conditions Index, US in children and adolescents after invasive treatment for
Department of Health and Human Services, National Institutes congenital heart disease. J Pediatr Surg. 2008;43:534-39.
of Health, Revised July, 2011 21. Meijer A, Conradi HJ, Bos EH, et al. Prognostic association of
3. Verstappen A, Pearson D, Kovacs AH. Adult congenital heart depression following myocardial infarction with mortality and
disease: the patient’s perspective. Cardiol Clin. 2006;24: cardiovascular events: a meta-analysis of 25 years of research.
515-29. Gen Hosp Psychiatry. 2011;33:203-16. Epub 2011 Mar 31.
4. Gantt LT. Growing up heartsick: the experiences of young 22. Goffman E. In Stigma: Notes on the Management of Spoiled
women with congenital heart disease. Health Care Women Int. Identity. New York, Simon and Schuster, Inc. 1963.
1992;13:241-8. 23. Kovacs AH, Bendell KL, Colman J, et al. Adults with
5. Horner T, Liberthson R, Jellinek MS. Psychosocial profile of congenital heart disease: psychological needs and treatment
adults with complex congenital heart disease. Mayo Clin Proc. preferences. Congenit Heart Dis. 2009;4:139-46.
2000;75:31-6. 24. Spiegel D, Sephton SE, Terr AI, et al. Effects of psychosocial
835
6. Kokkonen J, Paavilainen T. Social adaptation of young adults treatment in prolonging cancer survival may be mediated by
with congenital heart disease. Int J Cardiol. 1992;36:23-9. neuroimmune pathways. Ann N Y Acad Sci. 1998;840:674-83.
http://vip.persianss.ir
10 25. Martin A, Volkmar FR (Editors). In Lewis’s Child and
Adolescent Psychiatry: A comprehensive textbook, 4th edition.
30. Tousoulis D, Antonopoulos AS, Antoniades C, et al. Role of
depression in heart failure—choosing the right antidepressive
Philadephia, Lippincott Williams and Wilkins. 2007. p. 389. treatment. Int J Cardiol. 2010;140:12-8. Epub 2009 Jun 6.
Congenital Heart Disease in Adults
26. Mahler MS. Rapprochement subphase of the separation 31. Watson K, Summers KM. Depression in patients with heart
individualization process. Phychoanal. Q. 1972;41:487-506. failure: clinical implications and management. Pharmacothera-
27. Schotte CK, Van Den Bossche B, De Doncker D, et al. A py. 2009;29:49-63.
biopsychosocial model as a guide for psychoeducation 32. Milani RV, Lavie CJ, Mehra MR, et al. Impact of exercise
and treatment of depression. Depress Anxiety. 2006;23: training and depression on survival in heart failure due to
312-24. coronary heart disease. Am J Cardiol. 2011;107:64-8.
28. O’Connor CM, Jiang W, Kuchibhatla M, et al. SADHART- 33. Spencer T, Biederman J, Coffey B, et al. A double-blind com-
CHF Investigators.Safety and efficacy of sertraline for parison of desipramine and placebo in children and adoles-
depression in patients with heart failure: results of the cents with chronic tic disorder and comorbid attention-deficit/
SADHART-CHF (Sertraline Against Depression and Heart hyperactivity disorder. Arch Gen Psychiatry. 2002;59:649-56.
Disease in Chronic Heart Failure) trial. 25. J Am Coll Cardiol. 34. Swanson JR, Jones GR, Krass elt W, et al. Death of two subjects
2010;56:692-9. due to imipramine and desipramine metabolite accumulation
29. Goodlin SJ. Sadness in heart failure: what is a clinician to do? during chronic therapy: a review of the literature and possible
J Am Coll Cardiol. 2010;56:700-1. mechanisms. J Forensic Sci. 1997;42:335-39.
836
Sec t i on
11
Electrophysiological Issues
in Children
http://vip.persianss.ir
C hapter
http://vip.persianss.ir
11 BradyarrHytHmIa rElatEd to aBnormal
av nodE FunCtIon
ElEctrophysiological issuEs in childrEn
Figure 1: Sinus pause of 1.6 s. This pause could be due to abnormality First-degree av Block
in automaticity of sinus node (sinus arrest) or conduction from the
node to atrium (sinus exit block)
During first-degree heart block, conduction time across
AV node is prolonged resulting in prolonged PR interval in
Sinus Pause ECG; but all impulses are conducted. Clinically important
PR interval prolongation can result from a conduction delay
Sinus pause or absence of an expected P wave for more in the AV node (A-H interval), in the His-Purkinje system
than 3 seconds, may be due to sinus arrest (failure of the SN (H-V interval) or at both sites. Occasionally, an intra-atrial
pacemaker cells to depolarize) or be the result of sinoatrial conduction delay can also result in PR prolongation. Increase
(SA) exit block (depolarization of the SN but failure to conduct in atrial rate or vagal tone can cause first-degree AV nodal
to the atria). The main feature to look for in electrocardiogram block to progress to type I second-degree AV block. Isolated
(ECG) is P-P interval delimiting the pause does not equal a first-degree AV block warrants no treatment.
multiple of the basic P-P interval. In patients with sick sinus
syndrome, characterized by marked sinus bradycardia or Second-degree av Block (mobitz type I and type II)
sinus arrest, especially if symptomatic, permanent pacing is
necessary (Figure 1). Blocking of some atrial impulses conducted to the ventricle
Electrocardiogram in SA exit block shows a pause resulting at a time when physiological interference is not involved
from absence of the normally expected P wave. The duration constitutes second-degree AV block. Second-degree heart
of the pause is a multiple of the basic P-P interval. Sinoatrial block occurs in two forms, Mobitz type I (Wenckebach) and
exit block is caused by a conduction disturbance during which type II (Figures 2 and 3). Type I heart block is characterized
an impulse formed within the SN fails to depolarize the atria by a progressive lengthening of the conduction time until
or does so with delay. Excessive vagal stimulation, acute an impulse is not conducted. Electrocardiographically,
myocarditis or fibrosis involving the atrium, as well as drugs type I second-degree AV block is characterized by progressive
such as beta blockers or digitalis, can produce SA exit block. PR prolongation culminating in a non-conducted P wave.
Sinoatrial exit block can be of three types. A first-degree SA During a type I block, the increment in conduction time is
block cannot be recognized on the surface ECG. Second- greatest in the second beat of the Wenckebach group and the
degree SA blocks are recognized frequently because of their absolute increase in conduction time decreases progressively
effect on the atrial rhythm. Analogous to second-degree AV over subsequent beats. In type I second degree AV block,
block, there are two types of second-degree SA block: type I the interval between successive beats progressively
(Wenckebach periodicity) and type II, manifested by dropped decreases, although the conduction time increases (but by
P waves during sinus rhythm. Type I block is clinically more a decreasing function). The duration of the pause produced
prevalent than type II block. Sinoatrial exit blocks are usually by the non-conducted impulse is less than twice the interval
transient and usually do not require treatment. preceding the blocked impulse and the cycle following the
non-conducted beat is longer than the cycle preceding the
Sick Sinus Syndrome blocked impulse.
Type II heart block denotes occasional or repetitive
Sick sinus syndrome is a term applied to a syndrome sudden block of conduction of an impulse, without prior
encompassing a number of primary sinus nodal abnormalities, measurable lengthening of conduction time. In ECG, the
including sinus bradycardia, sinus arrest or exit block, PR interval remains constant prior to the blocked P wave.
AV conduction disturbances and alternation of atrial Type II AV block indicates disease in the infra-Hisian
tachyarrhythmias especially atrial fibrillation and periods conduction system and often antedates the development of
of slow atrial and ventricular rates (tachy-brady syndrome). Adams-Stokes syncope and complete AV block, whereas
Permanent pacing for the bradycardia, combined with drug type I AV block with a normal QRS complex is generally
therapy to treat the tachycardia, is required in those with benign and does not progress to advanced heart blocks (Refer
840 symptomatic tachycardia-bradycardia syndrome. indications for pacing given below).1
59
Figure 3: Mobitz type II second-degree AV block. Intermittently P wave fails to conduct, but not preceded
by prolongation of PR interval, unlike in Figure 2
2:1 atrioventricular Block occurring above the block with retrograde atrial conduction.
The ventricular focus is located below the region of the block,
The 2:1 AV block can be a form of type I or type II second which can be above, at or below the His bundle bifurcation.
degree AV block (Figure 4). If the QRS complex is normal, the Complete AV block can result from block at the level of the AV
block is more likely to be type I and located in the AV node. If a node; also known as suprahisian (usually congenital), within
bundle branch block is present, the block can be located in the the bundle of His or intrahisian or distal to it in the Purkinje
AV node or His-Purkinje system. An EP study may be required system or infrahisian (usually acquired). The ventricular rate
to localize the exact location of block with certainty. in acquired complete heart block is generally less than 40 bpm,
but can be faster in congenital complete AV block. Ventricular
third-degree (Complete) av Block pacemaker activity that are in or closer to the His bundle result
in a faster escape rate than can those located more distally in
Third-degree or complete AV block occurs, when no atrial the ventricular conduction system. Escape rhythm resulting
activity is conducted to the ventricles and the atria and ventricles from conduction block in infrahisian conduction system is
are controlled by independent pacemakers (Figure 5). The atrial slower and much more unstable (See below for indications for 841
pacemaker can be sinus or ectopic atrial or from AV junction pacing).1
http://vip.persianss.ir
11
ElEctrophysiological issuEs in childrEn
Figure 4: 2:1 AV block. Conducted PR interval and the QRS width often give clue to the likely site of AV block in these cases
Figure 5: Complete heart block. This condition is easily identified by PP association, RR association,
PR dissociation and atrial rate exceeding the ventricular rate
BradyarrHytHmIaS: SPECIal ConSIdEratIonS block may develop varying degrees of exercise limitation or
In CHIldrEn syncope. Sudden death is uncommon during the first decade,
but increases thereafter. Syncope or sudden cardiac death due
Clinical Presentation to complete AV block may result from bradycardia, per se or
bradycardia-dependent polymorphic ventricular tachycardia
Children presenting with symptoms owing to primary with degeneration to ventricular fibrillation (Figure 6).
bradycardias are relatively uncommon. Symptoms associated
with sinus node dysfunction are caused by inadequate heart Clinical Scenarios
rate response to stress or exertion. Overt symptoms are
relatively uncommon in children with first- and second- The common clinically significant bradyarrhythmias secondary
degree AV block too. However, complete heart block, either to conduction system disturbances and relevant in children can
congenital or acquired, can have a fatal outcome in children be grouped into the following main categories:
and may need more attention. 1. Sinus node dysfunction, which is secondary to surgical
The fetus and infant with congenital complete AV block repair of congenital heart disease (CHD), often with
and no associated heart disease usually are asymptomatic. concomitant atrial tachyarrhythmias.
However, if the escape rate is inadequate, symptoms may 2. Postsurgical atrioventricular block.
range from growth retardation to overt congestive heart failure, 3. Congenital atrioventricular block.
842 including hydrops fetalis. Older patients with congenital AV 4. AV conduction disturbances in Long QT syndrome (LQTS).
59
Postsurgical Sinus Node Dysfunction with or without Atrial of an episode of atrial tachycardia may be followed by a very
Tachyarrhythmias prolonged asystolic episode in patients with profound SN
dysfunction, leading to syncope. Drugs such as beta-blockers
Surgery for CHD often involves large incisions in the right and amiodarone generally have only negligible serious
atrium and in certain types of operations, the SN can be adverse effects in the presence of a normal SN. But when they
damaged.2,3 The SN may be damaged directly by incision, are given to patients with pre-existing SN disease, profound
clamping or suturing. Interruption of the blood supply to abnormalities of SN function can result.
the SN during surgery can also cause SN dysfuncion. Both
the Mustard and the Senning procedure for atrial redirection Postsurgical Atrioventricular Block
in d-transposition of the great vessels involve extensive
atrial suture lines and the incidence of SN abnormalities The surgical repair for CHD carries some risk of damage to
progressively increases as these patients grow into adulthood. either AV node or the distal conduction system. For example,
These two classical surgeries are not regularly performed in patients with perimembranous ventricular septal defect
nowadays, as transposition is now managed by the arterial (VSD), the bundle of His perforates the central fibrous body to
switch procedure. Still, thousands of children and adults are emerge on the margin of the defect, before branching into right
alive today following the Mustard or Senning procedure and and left fascicles.5 Placement of the patch requires placing
most have some elements of SN abnormality. deep sutures into myocardium and the conduction system
Another operation that is commonly associated with is at risk. Surgical repair of tetralogy of Fallot and truncus
SN dysfunction is the Fontan procedure. The loss of sinus arteriosus also may injure the AV node or distal conduction
rhythm with subsequent junctional escape rhythm leads to AV system. For all surgery at all ages, this incidence is 1 percent
asynchrony. This loss of AV synchrony certainly has adverse to 2 percent6 but may well be higher in patients operated
consequences in a patient with Fontan circulation. In patient during the first year of life. Patients with endocardial cushion
with borderline hemodynamic function, it is advisable to defects (AV canal defects) are at even higher risk, as are those
consider permanent pacemaker to restore AV synchrony, even who have enlargement of their VSD as part of certain complex
if a more obvious indication such as syncope or chronotropic repairs.
incompetence is not present. Due to the presence of extensive Postoperative AV block may also be seen following repair
atrial incisions and suture lines, such patients are also at risk for of simple defects in the atrium, such as secundum atrial septal
the development of atrial tachyarrhythmias and in particular, defects, but in these situations, it is likely that it is the compact
intra-atrial reentrant tachycardia.4 The coexistence of these AV node which is damaged, rather than the distal conduction
tachyarrhythmias with significant SN dysfunction is especially system. Postoperative AV block often resolves spontaneously
important. Episodes of tachycardia leads to hemodynamic within several days of surgery and such resolution may allow
instability and syncope and moreover, the sudden termination one to avoid placing of the pacemaker,7 even though some
843
http://vip.persianss.ir
11 of them may require temporary pacing support. AV block pacemaker for all, but a consensus is not yet there and many
persisting beyond 14 days is a clear indication for permanent believe this is unnecessary. In real world scenario, large
pacing. This is related to the poor prognosis of such patients prospective randomised studies in children with congenital
ElEctrophysiological issuEs in childrEn
and the potential for syncope and sudden death. It should AV block to assess the unintervened natural history may
be noted here that the observation of a seemingly adequate not be possible because of multitude of reasons. Hence, the
heart rate in the presence of postsurgical complete AV block recommendations are often supported only by evidence from
should not be seen as reassuring, as such escape rhythms retrospective observations. It is interesting to note that not a
are notoriously unreliable, particularly those with a wide single recommendation (Class I—III) in the current American
QRS complex. Unlike SN dysfunction, advanced AV block, College of Cardiology (ACC)/American Heart Association
especially with a wide QRS escape is potentially fatal. (AHA) guidelines for pacing in bradycardia is backed up by
level of evidence A.1 However, the older the patient, the more
Congenital Atrioventricular Block reasonable this recommendation would be, due to the easier
and safer implant procedure in larger patients. Most (but not
Patients are considered to have congenital complete AV all) clinicians agree that daytime rates > 50 bpm in children
block, if AV block is present at birth or develops during the older than 1 year or long ventricular pauses (defined recently
first year of life. Anatomical disruption between the atrial as at least twice the basic escape cycle length) are indications
musculature and peripheral parts of the conduction system and for pacemaker implantation in asymptomatic individuals.
nodoventricular discontinuity are two common histological
findings. Most cases of complete congenital AV block are Atrioventricular Conduction Disturbances in LQTS
related to maternal mixed connective tissue disease and/or
systemic lupus erythematosus.8,9 Mothers of affected infants The congenital LQTS is a potentially lethal disease caused by
have abnormally high titers of antibodies to the factors SS-A mutations in specific cardiac ion channels. LQTS is known to
and SS-B (anti-Ro and anti-La). A second group of infants cause 2 : 1 AV block in children when the refractory period
have congenital heart disease, especially l-transposition of the of the His-Purkinje system exceeds sinus cycle length. Rarely,
great vessels (congenitally corrected transposition). Finally, it can manifest as first-degree or second-degree AV blocks as
there is a large group in whom the disease is idiopathic, some well (Figure 7). These episodes of transient AV dissociation
of whom may carry the NKX2.5 mutation.10 or ‘pseudo-AV block’ are due to the oscillations in refractory
Mortality from congenital AV block is highest in the period of infrahisian conduction system that are often initiated
neonatal period, is much lower during childhood and by atrial premature beat. A small subset of patients with LQTS
adolescence, and increases slowly later in life. Stokes-Adams with 2 : 1 AV block clinically manifests in the fetal or neonatal
attacks can occur in patients with congenital heart block at period and has been associated with a lethal prognosis. A
any age. It is difficult to predict the prognosis in an individual mortality rate greater than 50 percent in the first 6 months of life
patient. A persistent heart rate at rest of 50 beats/minute or and up to 67 percent by age 2 years has been reported in some
less correlates with the incidence of syncope and extreme series of patients with LQTS and 2 : 1 AV blocks. Suspicion
bradycardia can contribute to the frequency of Stokes-Adams for and detection of LQTS in children presenting with AV
attacks. The site of block may not distinguish symptomatic conduction disturbances in the immediate neonatal period
children, who have congenital or surgically-induced complete allow for close monitoring of high-risk infants. Shortening and
heart block from those without symptoms. Prolonged homogenization of refractoriness of His-Purkinje system with
recovery times of escape foci following rapid pacing and slow AAI (atrium paced, atrium sensed and pacemaker inhibited in
heart rates on 24-hour ECG recordings and the occurrence of response to sensed beat)pacing, potassium supplementation and
paroxysmal tachycardias may be predisposing factors to the beta blockers or other genotype-specific drugs like mexilitene
development of symptoms. often would be sufficient to prevent life-threatening torsades in
Infants born to mothers with antinuclear antibody majority. In our experience, by this therapeutic approach, we
positivity may progress from second degree to complete could manage even refractory cases with excellent long-term
AV block during infancy. Some infants with complete follow up. The renewed interest in left cardiac sympathetic
congenital AV block will present in utero with hydrops denervation, which can be performed with minimally invasive
fetalis. If they are born alive, pacing is clearly indicated. surgery, is increasingly offered to patients with refractory
Others may present with symptoms related to low heart torsades de pointes (TdP). However, smaller devices and
rates, such as syncope, near-syncope or documented exercise novel defibrillator configurations allow for implantation in
intolerance. Children with congenital complete heart block, the neonatal period in a rare case which would not respond to
who are symptomatic should receive permanent pacemaker the above mentioned measures. The technical feasibility of an
implantation. Indications for pacing and recommendations of epicardial system without incorporation of a large, restricting,
timing of pacing are difficult for those children who are totally epicardial defibrillation patch permits implantation in infants
844 asymptomatic. One school of thought is to implant permanent as small as 3.5 kg.
59
IndICatIonS For PaCIng ventricular rate less than 55 bpm or with CHD and a
ventricular rate less than 70 bpm (Level of Evidence: C).
Recommendations for Permanent Pacing in Children,
Adolescents and Patients With Congenital Heart Disease— Class IIa
ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy
of Cardiac Rhythm Abnormalities: Executive Summary: A 1. Permanent pacemaker implantation is reasonable for
Report of the American College of Cardiology/American patients with CHD and sinus bradycardia for the prevention
Heart Association Task Force on Practice Guidelines. of recurrent episodes of intra-atrial re-entrant tachycardia;
SND may be intrinsic or secondary to antiarrhythmic
Class I treatment (Level of Evidence: C).
2. Permanent pacemaker implantation is reasonable for
1. Permanent pacemaker implantation is indicated for congenital third-degree AV block beyond the first year of
advanced second- or third-degree AV block associated with life with an average heart rate less than 50 bpm, abrupt
symptomatic bradycardia, ventricular dysfunction or low pauses in ventricular rate that are 2 or 3 times the basic cycle
cardiac output (Level of Evidence: C). length or associated with symptoms due to chronotropic
2. Permanent pacemaker implantation is indicated for sinus incompetence (Level of Evidence: B).
node dysfunction (SND) with correlation of symptoms 3. Permanent pacemaker implantation is reasonable for sinus
during age-inappropriate bradycardia. The definition of bradycardia with complex CHD with a resting heart rate
bradycardia varies with the patient’s age and expected less than 40 bpm or pauses in ventricular rate longer than 3
heart rate (Level of Evidence: B). seconds (Level of Evidence: C).
3. Permanent pacemaker implantation is indicated for 4. Permanent pacemaker implantation is reasonable for
postoperative advanced second- or third-degree AV block patients with CHD and impaired hemodynamics due
that is not expected to resolve or that persists at least 7 days to sinus bradycardia or loss of AV synchrony (Level of
after cardiac surgery (Level of Evidence: B). Evidence: C).
4. Permanent pacemaker implantation is indicated for 5. Permanent pacemaker implantation is reasonable for
congenital third-degree AV block with a wide QRS unexplained syncope in the patient with prior congenital
escape rhythm, complex ventricular ectopy or ventricular heart surgery complicated by transient complete heart
dysfunction (Level of Evidence: B). block with residual fascicular block after a careful
5. Permanent pacemaker implantation is indicated for evaluation to exclude other causes of syncope (Level of
congenital third-degree AV block in the infant with a Evidence: B). 845
http://vip.persianss.ir
11 Class IIb optimal pacemaker, limited venous access, and the anticipated
problems in long-term follow-up.
1. Permanent pacemaker implantation may be considered for
ElEctrophysiological issuEs in childrEn
transient postoperative third-degree AV block that reverts Medicine knows no limits, especially not its own.
to sinus rhythm with residual bifascicular block (Level of —Kocher, Gerhard
Evidence: C).
2. Permanent pacemaker implantation may be considered for rEFErEnCES
congenital third-degree AV block in asymptomatic children or
adolescents with an acceptable rate, a narrow QRS complex 1. Epstein AE, Dimarco JP, Ellenbogen KA, et al. 2012 ACCF/
and normal ventricular function (Level of Evidence: B). AHA/HRS Focused Update Incorporated Into the ACCF/
3. Permanent pacemaker implantation may be considered AHA/HRS 2008 Guidelines for Device-Based Therapy of
Cardiac Rhythm Abnormalities: A Report of the American
for asymptomatic sinus bradycardia after biventricular
College of Cardiology Foundation/American Heart
repair of CHD with a resting heart rate less than 40 bpm or Association Task Force on Practice Guidelines and the
pauses in ventricular rate longer than 3 seconds (Level of Heart Rhythm Society. Circulation. 2013 Jan 22;127:e283-
Evidence: C). 352.
2. Lewis AB, Lindesmith GG, Takahashi M, et al. Cardiac rhythm
Class III following the Mustard procedure for transposition of the great
vessels. J Thorac Cardiovasc Surgery. 1977;73:919-26.
1. Permanent pacemaker implantation is not indicated for 3. Bharati S, Molthan ME, Veasy LG, et al. Conduction system
transient postoperative AV block with return of normal AV in two cases of sudden death two years after the Mustard
procedure. J Thorac Cardiovasc Surgery. 1979;77:101-8.
conduction in the otherwise asymptomatic patient (Level of
4. Kalman JM, VanHare GF, Olgin JE, et al. Ablation of‘incisional’
Evidence: B). reentrant atrial tachycardia complicating surgery for congenital
2. Permanent pacemaker implantation is not indicated for heart disease. Use of entrainment to define a critical isthmus of
asymptomatic bifascicular block with or without first- conduction. Circulation. 1996;93:502-12.
degree AV block after surgery for CHD in the absence of 5. Anderson RH, Wilcox BR. The surgical anatomy of ventricular
prior transient complete AV block (Level of Evidence: C). septal defect. J Card Surgery. 1992;7:17-35.
3. Permanent pacemaker implantation is not indicated for 6. Bonatti V, Agnetti A, Squarcia U. Early and late postoperative
asymptomatic type I second-degree AV block (Level of complete heart block in pediatric patients submitted to open-
Evidence: C). heart surgery for congenital heart disease. Pediatr Med Chir.
1998;20:181-86.
4. Permanent pacemaker implantation is not indicated for
7. Vetter VL, Horowitz LN. Electrophysiologic residua and
asymptomatic sinus bradycardia with the longest relative sequelae of surgery for congenital heart defects. Am J Cardiol.
risk interval less than 3 seconds and a minimum heart rate 1982;50:588-604.
more than 40 bpm (Level of Evidence: C). 8. Chameides L, Truex RC, Vetter V, et al. Association of maternal
systemic lupus erythematosus with congenital complete heart
ConCluSIon block. N Engl J Med. 1977;297:1204-7.
9. Litsey SE, Noonan JA, O’Connor WN, et al. Maternal
The presence of bradyarrhythmia in children requires special connective tissue disease and congenital heart block.
care as symptoms are minimal. The transient, functional Demonstration of immunoglobulin in cardiac tissue. N Engl J
Med. 1985;312:98-100.
abnormalities has to be differentiated from primary disease
10. Benson DW, Silberbach GM, Kavanaugh-McHugh A, et al.
of the conduction system. The confounding factors related to
Mutations in the cardiac transcription factor NKX2.5 affect
associated structural heart disease, also need to be addressed. diverse cardiac developmental pathways. J Clin Invest.
Decision to pace needs consideration of issues like selection of 1999;104:1567-73.
846
C hapter
60 Tachyarrhythmias
Sathish S
EpidEmiology the AV node, there is rapid conduction via the specialized His-
Purkinje system with associated right and left bundle branches
Arrhythmias occur less commonly in childhood, constituting that intercalate to the ventricular myocardium.
5 percent of the emergency admissions in the pediatric
population.1 Majority of these tend to be accessory pathway mEChanism of TaChyCardia
mediated supraventricular tachyarrhythmias such as Wolff-
Parkinson-White (WPW) syndrome.2 The non-accessory re-entry
pathway mediated supraventricular tachyarrhythmias commonly
seen in children are atrioventricular nodal re-entry tachycardia Re-entry is a depolarizing wave traveling through a closed
(AVNRT), junctional ectopic tachycardia (JET) and automatic path.
ectopic atrial tachycardia (AT). JET and AT occur mostly in There are three prerequisites for re-entry:
the postoperative period after intracardiac repair for a structural 1. At least two pathways: Slow and fast AV nodal pathways,
heart defect. Ventricular tachycardia (VT) although uncommon, accessory pathway or the presence of barrier (anatomic:
occurs in the pediatric age group in association with hypertrophic tricuspid valve; pathologic: incisional scars, myocardial
cardiomyopathy, long QT syndrome (LQTS) and Brugada infarction and functional scar).3
syndrome. Occasionally, VT can also present symptomatically 2. Unidirectional block: This block can be physiological,
as incessant idiopathic infant VT, right ventricular outflow caused by a premature complex or increased heart rate or
tract (RVOT) tachycardia, catecholaminic VT, idiopathic left pathological, caused by changes in repolarization gradients.
ventricular tachycardia and in postcardiac surgical patient. 3. Slow conduction to prevent collision of the head and the
Supraventricular tachycardia (SVT) is the most common tail of the depolarizing wave: Physiologic caused by AV
rhythm disturbance in children. It is estimated to occur in as nodal slow pathway in AVNRT; cavotricuspid isthmus
many as 1 in 250 otherwise healthy children. Episodes are in atrial flutter (AFL), slow conduction across the crista
often recurrent although rarely life threatening. Treatment of terminalis in upper loop tachycardia; pathologic—ischemic
this disorder has undergone a remarkable transformation in or remodeled cells in atrium and ventricle (ventricular
the past quarter century with the advent of radiofrequency tachycardia, atrial flutter).
ablation (RFA). Although, SVT accounts for a small proportion In functional re-entry, unidirectional block can be due to
of children treated in an outpatient setting, the prevalence is dispersion of refractoriness (repolarization) or dispersion
high enough that most general pediatric practitioners will at of conduction velocity (anisotropic re-entry).The former
some point, care for a patient with this disorder. can be caused by repolarization gradients due to spatial
In the normal heart, the atrial and ventricular myocardium heterogenicity of repolarization (ischemia, drugs), discordant
are electrically insulated from one another except at the repolarization alternans (T-wave alternans during ischemia,
atrioventricular (AV) node and bundle of His. Impulse autonomic abnormalities) and transmural gradients from cell-
generation typically originates in the sinus node and the to-cell uncoupling (drugs, heart failure).
impulse is conducted through the atrial myocardium to the AV
node. The major role of this structure is to allow conduction Triggered activity
of the impulse to the ventricle; however, equally important is
the inherent delay in the AV node that slows conduction from Triggered activities are caused by after depolarization
the atrium to the ventricle, allowing ventricular filling. From currents. They are classified as early after depolarisation
http://vip.persianss.ir
11 (EAD), occuring inside the action potential (phase 2 and 3) However, the prevalence of structural congenital heart disease
and delayed after depolarisation (DAD) occuring in phase 4 of in patients with SVT has been estimated at 9 to 32 percent,
the action potential.4 These currents can in turn be responsible which is substantially higher than in the general population.
ElEctrophysiological issuEs in childrEn
for both focal and reentrant arrhythmias. The former is caused The most common association is noted between WPW
by eliciting an excitatory response exceeding the activation syndrome and the Ebstein anomaly of the tricuspid valve, but
threshold and the latter can develop when these currents a number of defects have been found, including ventricular
cause prolongation in action potential, which facilitates the septal defects (VSDs) or atrial septal defects (ASDs), among
development of a unidirectional block due to dispersion of others.
refractoriness.
EValUaTion
automaticity
history
Automaticity is driven by spontaneous phase 4 depolarization.
Automatic depolarizations in the atria and ventricles are not The clinical presentation of SVT is age and duration dependent.
manifested normally due to overdrive suppression by the faster In infants with paroxysmal SVT, the heart rate is usually 220
depolarization caused by the sinoatrial node. However, during to 320 beats/minute; in older children, it is 160 to 280 beats/
excess catecholaminergic states, phase 4 depolarization may minute. In infants, symptoms are usually nonspecific and
exceed sinus node depolarization, causing depolarization to be include poor feeding, irritability, vomiting, cyanosis and pallid
driven by the abnormal tissue.Ventricular tachycardias during spells. If the symptoms are unrecognized for hours to days, the
the acute ischemic and reperfusion phases are good examples infant can present with significant hemodynamic compromise
of automaticity. They often originate from the border zone or heart failure symptoms.7 It is rare for infants who have SVT
between normal and ischemic cells. for less than 24 hours to develop signs of congestive heart
failure at the time of presentation; however, congestive heart
supraventricular Tachycardia failure is present in 19 percent of infants who have SVT for
24 to 36 hours and in 50 percent who have SVT for more
Supraventricular tachycardia is broadly defined as a narrow, than 48 hours.8 Approximately, 20 percent of infants receive
complex tachycardia that requires atrial tissue or the AV a diagnosis during routine. In verbal children with SVT,
node as an integral part of the arrhythmia substrate, with the palpitations and fluttering in the chest are the usual presenting
exceptions of SVT in presence of existing or functional bundle symptoms.9 Because re-entrant arrhythmias are a circuit, they
branch block, antidromic atrioventricular reentry tachycardia tend to be all or nothing and the onset is frequently described
(AVRT), atrial fibrillation (AF) with bystander pathway as being abrupt, similar to a light switch being turned on.
conduction which are broad complex tachycardias. The The offset may be less dramatic because the catecholamine
majority (90%) of the clinically important SVTs in otherwise level is typically elevated, with resultant sinus tachycardia
healthy children are caused by the presence of an additional at the termination of SVT and subsequent gradual slowing.
(or accessory) electrical connection between the atrium and Frequently, lightheadedness and dizziness due to transient
ventricle (i.e. the bundle of Kent) or within the AV node itself. hypotension can occur at the onset, but syncope is rare in SVT
and its presence should raise suspicion of something other
inCidEnCE than SVT. The frequency and duration of the episodes vary
greatly from a few minutes to a few hours and occur as often
The true incidence of SVT in children is unknown, but as daily or as infrequently as once or twice per year. Although,
has been estimated to be 1 in 250 to 1 in 1000 children.5 rare in verbal children, incessant SVT symptoms may go
Approximately, 50 percent of children with SVT will present unrecognized until cardiac dysfunction develops.
with their first episode in the first year of life. After infancy,
the incidence peaks in early childhood (ages 6–9 years) and diagnosis
then again in adolescence.6 In infants, spontaneous resolution
occurs in more than 90 percent by 1 year of age. After a Recording a heart rhythm strip during symptoms remains the
period of quiescence, upto one-third will have recurrence of key to correct diagnosis and management. Options for this
SVT at a mean age of 8 years. Only a small minority (15%) include 24-hour ambulatory monitoring, event recorders and
of patients who are diagnosed after 1 year of age will have electrocardiograms (ECGs). Each of these means of obtaining
spontaneous resolution. Supraventricular tachycardia due a recording have associated advantages and disadvantages.
to concealed or manifest accessory pathways, predominates The Holter monitor provides a continuous multichannel
throughout childhood and adolescence, whereas the relative recording that usually allows the interpreter to see the whole
proportion of patients with AVNRT tends to increase with age. episode, including onset and termination. Most patients,
848 Most individuals with SVT have a structurally normal heart. however, do not have daily symptoms, making the Holter
monitor typically impractical in the evaluation of SVT. Event and 0.3 mg/kg at 5 minutes intervals, if hemodynamically 60
recorders are often the optimal solution for patients who have stable and no response. Up to 90 to 95 percent of AVNRT
symptoms more than once per month. Patients can wear the and AVRT respond and 30 to 35 percent of atrial tachycardias
tachyarrhythmias
monitor (loop recorder) or carry it with them (event monitor). respond to this therapy. In patients with AT, by blocking
In both cases, patients activate the recording device during AV node, AT is uncovered AT as the cause of tachycardia,
symptoms. The advantage of the loop recorder is that the however automatic AT may terminate with adenosine
recording encompasses the time before, during and after the (Figure 1). Verapamil (0.1–0.3 mg/kg over 2 minutes,
monitor activation. Finally, for infrequent episodes lasting may be repeated after 15 minutes with a maximum dose
longer than 10 minutes, patients can often be referred to the 5 mg first and 10 mg second dose) and diltiazem are effective
local emergency department for acute monitoring. in terminating AV node-dependent tachycardias in 90 percent
of cases. Verapamil should not to be used in children < 1 year,
management because it causes profound hypotension. Amiodarone (5 mg/
kg) and procainamide (15 mg/kg) can be infused slowly over
Acute Management 30 to 60 minutes with careful ECG and pressure monitoring
in stable patients not responding to above maneuvers.
Acute management of regular narrow QRS (<90 ms or
<0.09 s) nodal dependent (AVRT and AVNRT) tachycardias Long-term Management
depends on how well the tachycardia is tolerated, presence
of underlying heart disease and the response to therapy The management of SVT has many variables that need to
previously. If hemodynamically unstable, synchronized be considered, including the age of the patient, the duration
cardioversion is done at 1 to 2 Joules/kg with pediatric paddles, and frequency of the episodes and the presence of ventricular
if weight is less than 15 kg. Vagal maneuvers, including dysfunction. For children with rare and mildly symptomatic
carotid sinus message, Valsalva and Muller maneuvers, episodes in whom SVT is easily terminated, the SVT may
gagging and in case of infants exposing the face to ice cold not merit treatment. For children with episodes that are
water is helpful in hemodynamically stable patients. Acute difficult to terminate, occur frequently or occur during athletic
management of AVNRT and orthodromic atrioventricular participation, it may be advisable to offer medical therapy or
reentry tachycardia (OAVRT) is the same, except in case of transcatheter ablation as therapeutic options. Infants with SVT
AF with accessory pathway conduction and in antidromic deserve special recognition in regard to treatment options.
AVRT; drugs which prolong refractory period of pathway Most infants will undergo spontaneous resolution of SVT.
is given along with AV node blocking drugs. Digoxin and When this is combined with the increased risk of transcatheter
calcium channel blockers (CCB), which shorten the refractory ablation in this age group, medical management is preferred;
period are to be avoided. If vagal maneuvers fail, adenosine ablation is preferred in presence of tachycardiomyopathy, or
is the initial drug of choice given at 0.1 mg/kg, 0.2 mg/kg aborted sudden cardiac death (SCD).
Figure 1: Responses of narrow complex tachycardias to adenosine.10 AT = Atrial tachycardia; atrial tachycardia; AV =
Atrioventricular; AVNRT = Atrioventricular nodal reciprocating tachycardia; AVRT = Atrioventricular reciprocating tachycardia; 849
IV = Intravenous; QRS = Ventricular activation on ECG; VT = Ventricular tachycardia
http://vip.persianss.ir
11 medical Therapy • WPW and syncope with a shortest prexcited R-R lesser
Optimal medical management (in terms of whom to treat, with than 250 ms
which medication and for how long) of SVT in infants and • Chronic or recurrent SVT with ventricular dysfunction
ElEctrophysiological issuEs in childrEn
children has not been well studied and most current clinical • Recurrent VT associated with hemodynamic compromise
practices are extrapolated from small studies of adults and and is amenable to RFA.
uncontrolled pediatric studies.11-13 The intended effect of anti- Class IIA indications, in which the majority are of the
arrhythmic medications is to slow conduction, preferentially opinion or data favors RFA, include
within one limb of the re-entrant circuit, thereby terminating • Recurrent and/or symptomatic SVT refractory to medical
the tachycardia as the circulating wave front encounters therapy and age greater than 4 years
refractory tissue. Nearly, all classes of antiarrhythmic agents • Impending congenital heart surgery when vascular or
have been used to treat SVT successfully. The approach to chamber access may be limited following surgery
antiarrhythmic therapy includes the daily prophylactic therapy • Chronic (greater than 6 months) or incessant tachycardia
and the single-dose ‘pill-in-the-pocket’ approach, whereby with normal ventricular function
medication is taken only during an acute episode. The pill-in- • Chronic or frequent recurrences of intraatrial reentrant
the-pocket approach requires an immediate-release medication tachycardia
and is appropriate for patients who have infrequent episodes • Palpitations with inducible SVT during an
that are prolonged, but well tolerated.14 In adults combination electrophysiological study (EPS).
of diltiazem (120 mg) and propronolol (80 mg) have had good Class IIB indications, in which there is a clear divergence
results compared to flecanaide. They need however to be of opinion regarding the need for RFA, include:
avoided in antidromic AVRT. • Asymptomatic WPW and age less than 5 years when the
In most cases, first-line therapy is directed at modifying risk/benefits of RFA have been explained to the family
the conduction properties of the AV node and includes • SVT, age less than 5 years, as an alternative to chronic
treatment with beta-blockers (propronolol 2–4 mg/kg, 2–4 medical therapy that has controlled the tachycardia
doses, maximum 16 mg/kg, metoprolol 1–3 mg/kg), CCBs • SVT, age less than 5 years,when medications, including
(diltiazem 1.5–2 mg/kg/24 hours, maximum 3.5 mg/kg/24 sotalol and amiodarone, have not controlled the tachycardia
hours, verapamil 4–8 mg/kg/24 hours, 3 divided doses) and or have resulted in intolerable side effects
digoxin (8–10 mcg/kg in 2 divided doses, from birth to 10 • Intra-atrial re-entrant tachycardia, 1–3 episodes per year
years; greater than 10 years 125 mcg/d) except in WPW requiring medical intervention
syndrome, with antidromic tachycardia when use of CCBs • AV node ablation for intra-atrial re-entrant tachycardia
and digoxin should be avoided.15 With medical therapy, there • One episode of VT with hemodynamic compromise and
is a significant reduction in the number of episodes, although amenable to RFA.
complete suppression is rare. Class III indications, in which there is agreement that RFA
Supraventricular tachycardia refractory to first-line is not indicated, include:
medications can often be controlled with more potent anti- • Asymptomatic WPW, age less than 5 years
arrhythmic agents such as flecainide acetate (2–4 mg/kg, • SVT, controlled with medication, age less than 5 years
tid), amiodarone (5 mg/kg/day), sotalol hydrochloride, pro- • Nonsustained and non incessant VT without ventricular
canamide (15–50 mg/kg, qid) or drug combinations. Sodium dysfunction
channel blockers such as flecainide are particularly effective • Nonsustained, asymptomatic SVT.
in controlling SVT, but these agents are generally avoided in
patients with structural or ischemic heart disease because of prognosis
the risk of proarrhythmia. Sotalol, an agent with beta-
receptor and potassium channel blocking properties, is In the absence of structural heart disease or cardiomyopathy, the
also quite effective, but can lead to QT prolongation and prognosis of SVT is believed to be excellent. WPW syndrome
proarrhythmia.16 Radiofrequency ablation is preferred in deserves special consideration with respect to prognosis
children weighing more than 15 kgs, in view of good success owing to the small, but real risk of SCD associated with this
and similar complication incidents as in adults.17 condition. The principal indicator of risk in adults with WPW
In 2002, a position statement was published by members syndrome is the presence of symptoms (e.g. palpitations and
of the Pediatric Electrophysiology Society and endorsed by syncope). Symptomatic patients with WPW syndrome have
the North American Society of Pacing and Electrophysiology. an estimated 3 to 4 percent lifetime risk (0.25% per year) of
(Friedman RA NASPE). Class I indications, in which there SCD.18 In children and adolescents, however, asymptomatic
is clear and consistent agreement that RFA will benefit the may be better termed as presymptomatic. It has been estimated
patient, included: that 55 percent of asymptomatic children and adolescents will
• WPW following aborted sudden death become symptomatic by 40 years of age. For this reason, all the
850
children or adolescents in whom WPW syndrome is identified 60
on an ECG, regardless of the presence of symptoms, should
be referred to a pediatric electrophysiologist for evaluation.
tachyarrhythmias
Patients with WPW accessory pathways, who are defined
as low risk on the basis of EPS findings appear to be at no
increased risk of SCD compared with the general population.
aTrial arrhyThmias
Atrial arrhythmias include atrial tachycardia, atrial flutter and
atrial fibrillation. All have in common the feature that they do
not require participation of the AV node or the sinus node or the
ventricles for maintenance of tachycardia. Atrial tachycardia,
therefore is unaffected by AV block, either spontaneous or
adenosine induced. Atrial tachycardia definition also excludes
other types of atrial arrhythmia such as atrial fibrillation and
atrial flutter (macro re-entry).
The label focal AT has been used recently to describe atrial
arrhythmias that originate from a point source or localized
area of the atrium. Such arrhythmias have also been known
as atrial ectopic tachycardia and ectopic AT. The term ‘focal
atrial tachycardia’ does not imply a mechanism, which may
be micro re-entry, automaticity or triggered activity, although
abnormal automaticity (as in atrial ectopic tachycardia) is the
most likely. The difference between AT and AFL is rate cutoff
of 240 to 250/minute and the presence of isoelectric baseline
in AT. This ECG classification has several limitations,
neither rate nor lack of isoelectric baseline is specific for
any tachycardia mechanism.19 Macro re-entry AT include AT Figure 2: Atrial tachycardia diagnosed after giving adenosine
not using cavotricuspid isthmus as a part of circuit. Those revealing 2:1 conduction (arrows show P wave). Intially there was 1:1
using cavotricuspid isthmus are called atrial flutter. Atrial conduction and there was difficulty in diagnosing the rhythm.
tachycardia is common at extremes of age constituting 15
percent of arrhythmias in pediatric population.
Atrial tachycardia can present in children as either A negative P wave in lead I or aVL or a positive P wave in
paroxysmal or incessant automatic AT. The anatomic lead V1, favors a left atrial origin, negative P waves in the
distribution is similar to adults—the ostium of pulmonary inferior leads are suggestive of a low atrial origin, whereas
veins, crista from sinus node to coronary sinus, left and right a positive P wave in those leads suggest a high atrial origin.
atrial appendage and less commonly along AV valve annuli.20 Atrial tachycardia from the high crista terminalis or right
It is a common cause for tachycardiomyopathy in pediatric superior pulmonary vein may resemble sinus P wave, but for
age group. the positive P wave in lead V1.
Electrocardiogram management
In ATs, the P waves are in the second half of the tachycardia Acute Treatment
cycle, hence obscured by the T wave of the preceding QRS
complex (Figure 2). The presence of AV block during tachycardia Atrial tachycardias may rarely be terminated with vagal
excludes AVRT and makes AVNRT very unlikely. During ATs, maneuvers and a proportion of focal ATs will terminate with
an isoelectric baseline is usually present between P waves and it administration of adenosine and the common response is AV
is used to distinguish AT from typical or atypical flutter (i.e. saw block, revealing atrial rate more than ventricular rate suggestive
toothed or sinusoidal P wave morphologies), however, it may not of AT. Class Ia or class Ic drugs may suppress automaticity or
hold true in congenital heart disease.The diagnosis of AT can be prolong action potential duration and hence, may be effective
established with certainty only by an electrophysiological study, for some patients with AT. Similarly, DC cardioversion
including mapping and entrainment. seldom terminates automatic ATs, but DC cardioversion may
P-wave morphology on the 12-lead surface ECG is useful be successful for those in whom the tachycardia mechanism 851
for the determination of the site of origin of the focal AT.21 is micro re-entry or triggered automaticity and should be
http://vip.persianss.ir
11 considered for patients with drug-resistant arrhythmia. often by one year of age. After neonatal presentation of
The usual acute therapy for AT consists of intravenous beta tachyarrhythmia, there is second peaking at 8 years of age.This
blockers or CCBs for either termination, which is rare or to may be related to functional changes in conduction properties,
ElEctrophysiological issuEs in childrEn
achieve rate control through AV block. Direct suppression of cardiac dimension changes, maturation of autonomic nervous
the tachycardia focus may be achieved by use of class Ia and system and increased physical activity. Those having neonatal
Ic or class III (e.g. sotalol, amiodarone) agents. Intravenous presentation, have recurrence of arrhythmia in 1/3 of cases,
class Ia or Ic agents may be taken by patients without cardiac but those presenting late have less chance of spontaneous
failure, whereas intravenous amiodarone is preferred for those resolution.
with poor ventricular function. Natural history studies are limited. In a study of 184
asymptomatic children, 38 percent developed tachyarrhythmia
Long-term Pharmacologic Therapy in next 2 years, 30 percent of them were life threatening.25 The
electrophysiological characterstics of these were antegrade
The available studies pertaining to long-term pharmacologic refractory period < 240 ms, presence of multiple pathways
therapy are observational and there are problems in discerning and inducibility of tachyarrhythmia. The risk of catastrophic
whether the tachycardias were carefully differentiated from events increased in presence of digoxin, caused by heightened
other mechanisms (i.e. AVRT or AVNRT) or from other forms adrenergic status.It is recommended that those children more
of ATs. Review of the available data supports a recommendation than 5 years of age with asymptomatic pre-excitation required
for initial therapy with CCBs or beta blockers because these to participate in competitive sport, needs the assessment
agents may prove to be effective and have minimal side effects. of antegrade refractory period of pathway by looking for
If these drugs are unsuccessful, then class Ia, class Ic (flecainide intermittent pre-excitation on ECG, Holter and disappearance
and propafenone) in combination with an AV-nodal-blocking of pre-excitation with treadmill test indicating poor antegrade
agent or class III agents (sotalol and amiodarone) may be tried conduction over pathway and low risk of SCD. If non-invasive
because they may prove to be effective. The potential benefit studies suggest good antegrade conduction over the pathway,
should be balanced by the potential risks of proarrhythmia and they may require invasive EPS for risk stratification and RFA,
toxicity.22,23 The infants less than three years are managed by if needed.25,26
medical means in view of spontaneous resolution in around 70
percent after 3 years and limitations of RFA, in view of size of mechanism of Tachycardia
child and complications.24 The preffered drug for arrhythmias
are amiodarone and sotalol. Children more than 3 years are The accessory pathway permits either only antegrade or
managed by RFA, in view of amenability to ablation and need retrograde or bidirectional conduction from the atria to the
for long-term medical management. ventricle. An early atrial extrasystole is conducted slowly
down the AV node to the His–Purkinje system and ventricle; it
Wolff-parkinson- WhiTE syndromE and returns to the atrium over the accessory pathway and then into
orThodromiC aVrT ventricle if AV node has recovered and is no longer refractory,
then a circus movement tachycardia, also known as re-entry
By definition, WPW syndrome means pre-excitation on tachycardia or reciprocating tachycardia, can be established,
ECG with tachycardia, either orthodromic, commonest of termed as OAVRT and antidromic AVRT if circuit is other way
the two where the pathway conducts retrogradely or anti- around. A ventricular extrasystole can also trigger tachycardia
dromic tachycardia, the pathway conducts antegradely. The in this situation, via retrograde conduction up the accessory
presentation may be in fetal life with tachycardia, requiring pathway into the atrium, with the retrograde P wave then
fetal auscultation or ultrasonography and confirmation of being conducted anterograde across the AV node. Following
the tachycardia rate by combination of M-mode, Doppler ventricular depolarization, there is conduction back up of the
and two dimensional echocardiography. These patients may accessory pathway and the tachycardia is initiated.25
present with hydrops fetalis, requiring aggressive treatment.
Medications used include digoxin; beta-blockers; CCBs and Electrocardiogram
classes I and III antiarrhythmics, either alone or in combination.
Variations in transplacental transport of medications complicate The baseline ECG may show delta wave if antegrade conduction
treatment of the fetus, coupled with side effects in the mother, occurs over the pathway, the degree of pre-excitation depends
who must be monitored closely for proarrhythmic effects such on how fast the pathway or the node conducts, septal and
as those seen with the class I and III agents. If the fetus does right-sided pathways show more pre-excitation as the sinus
not respond to medications in a timely manner and hydrops conduction reaches this site fast. The presence of intermittent
persists, premature delivery may be required. pre-excitation suggests weak antegrade conduction across the
Among neonates having WPW syndrome, approximately pathway and low risk of sudden death. The ECG showing
852 25 to 35 percent will experience disappearance of delta wave, different patterns of pre-excitation may indicate presence
of multiple pathways.There are different algorithms for inferior leads suggest inferior location of pathway, if positive 60
localization of the pathway with varing sensitivity and suggesting anterior location), ST depression in lateral leads
specificity, based on initial 20 to 60 ms of delta wave or the and ST elevation in aVR.29
tachyarrhythmias
morphology or polarity of entire QRS complex.27,28 All left
free wall pathways show positive delta in V1, with R greater management
than S in V1 or V2 at the latest. A negative delta wave in lead
I, aVL or V6 is suggestive of left free wall pathway. As the Neonates and infants with tachycardia are often very sick,
pathway moves from posterior to lateral and more anterior, presenting with congestive heart failure, in view of the infant’s
the delta waves in inferior leads III and aVF, change from inability to communicate and the family’s lack of awareness
negative to isoelectric to positive. A positive delta wave in V1, that the child could have a significant medical condition and
with R greater than S, suggests left-sided pathway and if R long lasting tachycardia. Parents may note that the infant was
lesser than S suggests either right free wall or minimally pre- acting somewhat different than normal, more irritable or not
excited left-sided pathway. A negative delta in V1 suggests eating well, often interpreted as colic or some other ‘normal’
septal pathway. Right-sided pathways are recognised by small childhood problem. At presentation, these babies often
R in V1, late transition at V3 or more and a positive delta are acidotic from decreased cardiac output and may need
wave in lead I and aVL. As the pathway moves from right aggressive resuscitation including artificial ventilation and
superior to lateral and inferior location, delta wave in III and rapid termination of the tachycardia. Intravenous adenosine
aVF changes from positive to isoelectric to negative. The is effective in the acute termination of SVT in this population,
tachycardia ECG may show regular narrow QRS tachycardia but intravenous access is often difficult in a 3 to 4 kg baby
if antegrade conduction occurs over the AV node, orthodromic in congestive heart failure. Transesophageal overdrive pacing
AVRT (Figure 3) and regular broad complex tachycardia if has proven very helpful. Once the rhythm is restored to normal
antegrade conduction occurs over the pathway, producing and the cardiac function has begun to recover, intravenous
antidromic AVRT. Irregular broad complex tachycardia access becomes easier and intravenous medications can be
occurs in AF with antegrade conduction over the pathway. employed.
The ECG signs to suggest OAVRT are the presence of distinct Digoxin, a first-line medication used in the treatment of
P wave in short RP tachycardia (the morphology of retrograde SVT in infants with decreased myocardial performance,
P depends on the site of pathway, positive in V1 or lead I is contraindicated in patients with WPW syndrome; Other
suggests right- sided pathway, negative P wave in all the three medications used acutely to treat SVT include intravenous
Figure 3: Regular narrow QRS short RP tachycardia with significant ST depression in lateral leads and elevation 853
in lead aVR and a subtle P wave immediately after QRS suggestive of orthodromic AVRT
http://vip.persianss.ir
11 beta-blockers such as intravenous esmolol, procainamide and
amiodarone. These medications must be used with caution
because of their negative inotropic effects, which can lead to
ElEctrophysiological issuEs in childrEn
management Electrocardiogram
854 In acute management intravenous adenosine or metoprolol The mechanism of the tachycardia accounts for the ECG
can be used. In drug refractory cases intravenous appearances. The QRS is normal for age and P waves are
management 60
Management of PJRT is influenced by the age and clinical
tachyarrhythmias
condition of the child at presentation. Antiarrhythmic drug
treatment is almost always used in infancy. If the function of
the left ventricle is significantly impaired, the drug of choice
is probably amiodarone. If ventricular function is satisfactory,
flecainide or propafenone will usually prove effective. Success
is also reported with oral verapamil, although beta-blockers
and digoxin are less effective. The aim of drug treatment is
suppression of the PJRT, although intermittent tachycardia at
low rates on Holter monitoring is acceptable. Once control or
suppression of tachycardia has been achieved, the ventricular
function will improve and usually return to normal. Spontaneous
resolution of PJRT is uncommon. In most, this is a long-term
problem requiring catheter ablation, with good results.38
855
Figure 6: Long RP tachycardia with inverted P wave in inferior and lateral leads
http://vip.persianss.ir
11 medical management, being the first choice. If unsuccessful, Paired ventricular pacing to decrease the ventricular rate
ablation of JET can be attempted in the region of fast pathway, has been used. intravenous amiodarone has been effective
preferably with cryoablation.41 in the treatment of these patients. In using intravenous
ElEctrophysiological issuEs in childrEn
prognosis
The PVCs and VT disappear over time in 37 to 65 percent of
patients with normal hearts. Sudden death is rare in normal
children with PVCs but has been reported.45 In children
with abnormal hearts, PVCs may be precursors of more
Figure 7: Congenital JET diagnosed in a child of 3 years after giving serious arrhythmias, especially if they are complex-multiform,
856 amiodarone infusion, revealing the onset of tachycardia by a junctional
coupled or associated with VT.
beat
Clinical signs and symptoms VT have been described, torsades de pointes and bidirectional 60
VT. Bidirectional VT shows beat-to-beat variation in the
Children under 5 years of age with PVCs are frequently QRS axis and is associated with digoxin toxicity, familial
tachyarrhythmias
asymptomatic and unaware of their arrhythmias. Older hyperkalemic paralysis or catecholamine sensitivity.46
children may complain of a skipped or hard beat or a fluttering
in their chest, while some perceive PVCs as painful. Clinical signs and symptoms
Electrocardiographic manifestations The data from the new born from Italy demonstrate that,
among whites, the prevalence of LQTS is at least 1 : 2534
The electrocardiographic diagnosis of VT is made most easily apparently healthy live births.48 In 1993, statistics from a
in the presence of a wide QRS tachycardia with AV dissociation. group of 287 children, the initial presentation was cardiac
Many children have ventriculoatrial (VA) conduction with arrest (9%), syncope (26%), seizures (10%), presyncope or
relatively rapid 1 : 1 retrograde VA conduction, and AV palpitations (6%), with 88 percent having exercise-related
dissociation may not occur. The differential diagnosis of broad symptoms, 39 percent were identified because of family
complex tachycardia is SVT in the presence of existing or history or the identification of other family members with
fuctional bundle branch block, antidromic AVRT, AFIB with the syndrome and 39 percent were asymptomatic.49 Of those
bystander pathway conduction which are broad complex asymptomatic, 4 percent experienced sudden death compared
tachycardias. It must be remembered that the normal QRS to 8 percent overall. The strongest predictors of sudden
duration in infants and young children is 40 to 80 ms, so a death were QTc greater than 0.60 and noncompliance with
wide QRS in an infant might only be > 80 ms. The rates of recommended medication. Bradycardia is commonly seen in
VT in pediatrics vary from 120 to 300 bpm. The presence of these patients, and some may develop or present with second-
PVCs during sinus rhythm with the same configuration as VT degree AV block.50 This is more common in neonates (Figure
is a suggestive sign. AV dissociation is suggestive of VT, but 8) who may have second- or third-degree AV block but it may
1 : 1 VA conduction is common, especially in young children. be seen in older children, especially with exercise.
Fusion beats are commonly noted at the onset or termination The abnormal genes that encode for proteins modulate
of the VT. VT may be sustained (greater than 30 consecutive potassium or sodium ion channels, causing the LQTS by
complexes) or nonsustained (3–30 consecutive complexes). altering cardiac repolarization and increasing the risk for
Further, differentiation is made according to the morphology, ventricular arrhythmias. These genes include KVLQTI,
with VT being described as monomorphic or polymorphic.The HERG, SCN5A, minK and MiRp1. Not all families with known
monomorphic VT classified as LBB or RBB morphology based LQTS have shown linkage to these known loci, suggesting the
on predominant polarity in lead V1. Two types of polymorphic presence of additional genes yet to be discovered. Apart from 857
http://vip.persianss.ir
11 table 1
Schwartz/Moss score for long QT syndrome (LQTS)
diagnostic criteria
ElEctrophysiological issuEs in childrEn
Variable Points
ECG findings
QTc mseca ≥ 480 3
460–470 2
450 (in males) 1
Torsade de pointes 2
T-wave alternans (macroscopic) 1
Notched T wave in three leads 1
Figure 8: Neonate with LQT presenting with CHB Low heart rate for ageb 0.5
Clinical history
Syncopec
repolarization abnormality, imbalance or oversensitivity of the With stress 2
myocardium to sympathetic stimulation appears to play a role Without stress 1
in the development of ventricular arrhythmias. The trigger Congenital deafness 0.5
for arrhythmia in the LQTS is believed to be spontaneous Family historyd
Family members with definite LQTSe 1
secondary depolarizations that arise during or just following
Unexplained sudden cardiac death < age 0.5
the prolonged plateau phase of action potentials, early after 30 years among immediate family members
depolarizations, which is augmented by increased sympathetic
aQTc calculated using Bazett’s formula (QTc = QT/square root of RR).
tone. bMutually exclusive.
cResting heart rate below the second percentile for age.
Clinical associations of genetic findings dThe same family member cannot be counted in both.
eDefinite LQTS is defined by an LQTS score greater than or equal to 3.5.
tachyarrhythmias
testing in children able to exercise. Exercise will generally of the IKs pathway.
obliterate sinus arrhythmia and a strip can be obtained in The two major protocols developed for epinephrine infusion
which a reasonable QTc calculation, if a good tracing free include the bolus and brief infusion developed by Shimizu, and
of disturbances be obtained. The recovery period with the escalating-dose protocol (Mayo protocol).59,60 Infusion
heart rates around 120 to130 bpm seems to demonstrate of epinephrine is initiated at 0.025 μg/kg/minute. After 10
the greatest degree of QTc prolongation in many patients. minutes of the infusion, QT/QTc, repeated. The epinephrine
Exercise may uncover abnormal T waves, polymorphic infusion was then increased sequentially every 5 min to 0.05,
PVCs, or VT.55,56 If suspicion for LQTS is high and other 0.1 and 0.2 μg/kg/minute and the measurements were repeated
testing has not been definitive, isoproterenol or epinephrine 5 minutes after each dose increase. The epinephrine infusion
infusion may help to identify these patients. Efforts to identify was then discontinued and measurements were obtained 5
patients at high risk for syncope and sudden death continue. and 10 minutes afterward. The total duration of epinephrine
High-risk electrocardiographic markers have included QTc infusion was 25 minutes. The change in the uncorrected
greater than 0.60, T wave alternans and QTc dispersion. QT QT interval and the change in QTc were calculated by the
dispersion, which indicates heterogeneity of repolarization, difference between the maximal and minimal QT and QTc,
could predispose to the development of torsades de pointes, respectively, at any time during the epinephrine infusion at a
patients not responding to beta-blocker had a significantly dose of 0.1 μg/kg/min. Established stopping criteria included
higher dispersion of repolarization than responders.57,58 T systolic blood pressure 200 mm Hg, NSVT or polymorphic
wave alternans is known to be a high risk factor. VT, ten PVCs per minute, T-wave alternans or patient
intolerance (Figure 9).
Epinephrine Challenge Test
Treatment
Physiological basis: In the normal heart, epinephrine increases
both inotropy and chronotropy. This is achieved in part by Emergent treatment of these patients includes lidocaine and
G-protein/cAMP/protein kinase A–mediated phosphorylation cardioversion. Magnesium may be used to treat torsades de
of IKs (slowly activating delayed rectifier potassium pointes; intravenous propranolol and phenytoin have also
channel) and the Ca activated Cl channel. IKs is one of the been successfully used in these patients.61 The class I agents,
dominant potassium channels responsible for repolarization which are known to prolong the QT interval in normal patients,
(particularly phase 3), which allows potassium ions to exit the should be avoided in these LQTS patients. This is related to
cell and action potential duration to shorten. Activation of this QTc prolongation with associated bradycardia or ventricular
channel explains the observed attenuation of the QT interval arrhythmias or both. Temporary pacing and removal of the
that occurs with epinephrine infusion in normal subjects. offending agent are effective therapies.62
LQT 1 with KCNQ1 mutations (LQT1) have compromised The standard long-term treatment in this condition is
IKs channels that are not as responsive to sympathetic the use of beta-blockers. Those most commonly used are
stimulation and phase 3 repolarization in these individuals propranolol and nadolol.63,64 Some have suggested long-
is retarded. Consequently, during epinephrine infusion, there acting metaprolol or atenolol. A concern about once-daily
are relatively more unopposed depolarizing forces via the dosing relates to the lowest levels being present in early
L-type calcium channel and the sodium calcium exchanger morning hours, a particularly high-risk time for some patients.
that prolong the action potential duration and hence the QT The dose of beta-blocker required is variable and is usually
interval. LQT2 with KCNH2 mutations have dysfunctional greater per kilogram in younger patients. The dose can be
rapidly activating delayed rectifier potassium (IKr) channels, titrated by the heart rate response to maximal exercise testing,
a smaller fraction of the potassium channels responsible aiming for a blunted maximal heart rate response on therapy
for phase 3 repolarization and are not as sympathetically of 150 to 160 bpm. Treatment with beta-blockers can lower
responsive as IKs channels. Therefore, in patients with LQT2, the mortality to less than 4 percent, with greatest benefit in
there may be a transient prolongation of the action potential LQT1.65 Patients are followed with exercise stress tests and
duration during epinephrine infusion, followed by a normal Holter monitoring to look for adequacy of treatment or the
abbreviation of the action potential duration and the absolute development of significant ventricular arrhythmias or both.
QT interval due to the presence of unimpaired IKs channels. Patients who do not respond to beta-blockers may be treated
This transient prolongation of the QT interval followed by with mexiletine, phenytoin or pacing. Mexiletine is more useful
shortening is a characteristic feature of the LQT2 phenotype. in LQT3 patients. Rarely, other antiarrhythmics may be used,
The LQT3 phenotype is characterized by a constant reduction but those known to prolong the QT interval should be avoided.
of the action potential duration with epinephrine due to Potassium supplementation especially in LQT2 therapy may 859
http://vip.persianss.ir
11
ElEctrophysiological issuEs in childrEn
Figure 9: Adrenalin challenge test in a child with family history of sudden cardiac death in the sibling showing increasing QTc
from base line value of 426 ms to 659 ms. This patient was later confirmed to have LQT1 gene defect
be helpful. Left stellate ganglionectomy is a treatment which that for most LQT1 grown-up patients, full-dose beta-
should be offered to all patients.66 Permanent pacing has been blockers might be sufficient. On the basis of additional
shown to be an effective adjunctive treatment in these patients, considerations, e.g. duration of the QT interval, this may
especially those with severe bradycardia either from the lead to an open discussion with patients and family
syndrome itself or from the beta-blocker therapy, tachycardias 3. Patients who continue to have syncope despite full-dose
which are triggered by pauses. The rate of the pacing should beta-blockade whenever the option of LCSD either is not
be at least 10 to 20 percent higher than the sinus rate and in available or is discarded after discussion with the patients
severe cases should control the rhythm as much of the time 4. All patients with two mutations who continue to have
as possible.67 Pauses should be avoided. Using this treatment, syncope despite beta-blockade
episodes of torsades de pointes may be reduced or eliminated. 5. Exceptionally, the rare asymptomatic patients with a QTc
In patients known to have had a cardiac arrest or frequent or 550 milliseconds who also manifests signs of high electric
significant syncope associated with ventricular arrhythmias, instability (e.g. T-wave alternans) or other evidence of
on beta blockers and left cardiac sympathetic denervation being at very high risk (e.g. very long sinus pauses that
(LCSD), implantation of an automatic internal cardioverter/ might favor early after depolarizations).
defibrillator device may be necessary. These devices can
recognize VT or VF according to programed criteria and Implantable Cardioverter-Defibrillator Complications
provide a series of shocks to convert the patient to sinus
rhythm. Some can provide backup pacing. Their size led to The relatively high rate of inappropriate shocks and
limited use in smaller children, but improved technology now complications after ICD implantation increases the morbidity
allows even small children to benefit from this technology. of this treatment modality in LQTS patients and worsens its
This is not a therapy to be undertaken lightly at this time, risk benefit ratio. Inappropriate shocks were caused mainly by
as follow-up and possible false discharges can significantly abnormal sensing resulting from either T-wave over sensing or
affect a child’s life and lifestyle. lead failure. The young age at implantation (76% of patients
At present following group of patients merit implantable lesser than 40 years of age, 12 percent lesser than 10 years of
cardioverter-defibrillator (ICD): age) supports the hypothesis that the high rate of lead failure
1. All those who have survived aborted cardiac arrest (ACA) is attributable to the activity-dependent increased strain on
on therapy ICD leads. Another cause of inappropriate shocks was SVT.
2. Many of those who have survived an ACA off therapy, Besides avoiding unnecessary shocks, prolonging the detection
860 except those with a reversible/preventable cause, but noting time and increasing the threshold of tachycardia detection
may reduce inappropriate shocks caused by supraventricular pathophysiology 60
or sinus tachycardia, especially in young patients. In 223
implants, there were 67 adverse events in 58 patients, the more The hypothesis that arrhythmias in CPVT are initiated by
tachyarrhythmias
severe adverse events resulted directly from the implantation DADs and triggered activity had been advanced based on
surgery such as lead placement issues, infections and vascular the observation that the bidirectional VT observed in CPVT
problems. Most of the minor complications were related to patients closely resembles digitalis-induced arrhythmias.
lead issues, including conductor fractures, insulation defects, Digitalis-induced intracellular Ca2 overload leads to the
and changes in electric characteristics.68 These findings activation of sodium–calcium exchanger that, in turn,
substantiate the concerns about the long-term impact of generates a net inward current (the so-called ‘transient inward’
implanting an ICD in young LQTS patients, likely to live ITi current). ITi underlies diastolic membrane depolarizations,
another 7 to 8 decades after initial device implantation and DADs, that may reach threshold for sodium current activation
who would be subject to multiple procedures for generator and trigger abnormal beats. This mechanism for arrhythmia
replacements and lead revisions/extractions with probable initiation is defined as ‘triggered activity.’
complications. This makes the implementation of loose and
non-data-based indications for ICD implantation in LQTS Clinical manifestations
patients no longer preferred.
It is generally recommended that competitive athletics be Syncope, triggered by exercise or emotional stress, is often
avoided by patients with LQTS and especially in those with the first manifestation of CPVT.69 Approximately 30 percent
documented LQTS symptoms or arrhythmias. However, as of patients present with a family history of stress-related
more ‘carriers’ or asymptomatic patients are being discovered, syncope, seizure, or sudden death. Most events occur in the
who have only a prolonged QT interval and no family history first or second decade of life. CPVT diagnosis is established
of sudden death or ventricular arrhythmias, individual exercise after an average delay of 2 years from the first syncope,
and sports participation recommendations may be made. because these events are often attributed to vasovagal events
The most important aspect of the care of these patients is or to neurological factors.70 Increasing evidence shows that
continued surveillance. This is true for young family members SCD can be the first manifestation of the disease.
who appear to have normal QT intervals on initial evaluation.
The QT interval changes with age with periodic ECGs, Electrocardiogram
hence appropriate 24 hours and exercise ECG should be done
in children and adolescent members of LQTS families in The resting ECG of CPVT patients is usually normal
whom the initial evaluation was negative, unless the genetic with the exception of prominent U waves and mild sinus
testing has definitively ruled out LQTS. It is recommended bradycardia in some patients, which is especially abnormal
that patients with LQTS avoid caffeine, adrenergic stimulants for children of this age. There is normal QTc, normal AV
such as epinephrine and over-the-counter stimulants such conduction and no evidence of a Brugada like pattern.
as decongestants. Medications that prolong the QT interval Exercise or acute emotional stress is the typical trigger
should be avoided. of CPVT-related arrhythmias, constantly at heart rate of
110 to 130 beats per minute.71 The complexity and frequency
CaTECholaminE-indUCEd VEnTriCUlar of ventricular arrhythmia progressively worsen with an
TaChyCardia increase in workload, from isolated premature beats to
bigeminy and to ventricular tachyarrhythmia (Figure 10).
Catecholamine-induced VT is a genetic disorder associated When the exercise stops, arrhythmias gradually disappear.
with stress-induced, bidirectional VT that may degenerate The most typical VT observed in CPVT patients presents
into VF and result in sudden death, in the absence of both an alternating QRS axis morphology with a rotation of 180
structural heart disease and a prolonged QT interval. The CPVT degrees on a beat-to-beat basis, the so-called bidirectional
phenotype most often shows an autosomal dominant pattern VT. In view of the role of triggered activity as a mechanism
of transmission, although sporadic cases seem to be rather for arrhythmias in CPVT, it is interesting to note that fast
frequent and a familial history of juvenile sudden death and SVT may act as a trigger for the development of DADs and
stress-induced syncope is present in about 30 percent of cases. triggered activity in the ventricle.
This condition usually occurs in childhood, adolescence or
young adulthood. Reports of mutation in the ryanodine receptor diagnosis
gene RyR1 mapped to 1q42-q43 have been found in families
with catecholamine-induced VT, a recessively inherited CPVT Exercise or emotion-induced syncope in a patient with a
phenotype and the disease locus to a 16-megabase interval normal ECG (normal QT interval) and without structural
on chromosome 1p13–21, calsequestrin 2 (CASQ2) gene abnormalities should always suggest the possibility of
mutation gives rise to a pathological clinical phenotype only in CPVT. An exercise stress test is the most important tool for 861
homozygous carriers, while heterozygous carriers are usually diagnosis since the bidirectional or polymorphic VT may be
silent. reproducibly elicited during physical activity in most of the
http://vip.persianss.ir
11
ElEctrophysiological issuEs in childrEn
Figure 10: Ventricular ectopics of different morphology in a child at baseline, developed polymorphic
ventricular tachycardia during stress test
patients. Furthermore, even in patients showing polymorphic malformations, sufficient to explain the degree of hypertrophy.75
(and not bidirectional) VT, the progressive worsening of The discovery that many patients with hypertrophic
arrhythmias with exercise is to be considered as diagnostic for cardiomyopathy had familial disease led to a search for the
CPVT. Invasive electrophysiological testing and isoprenaline genetic basis of the disease. In 1989, the first mutation in the
infusion are of not proven value. gene encoding the cardiac β-myosin heavy chain was identified.
Since then, more than 400 mutations have been identified in this
Treatment and other cardiac sarcomeric protein.
tachyarrhythmias
to 8 percent per year, but recent population-based reports for the treatment of atrial fibrillation.
from Australia and the United States report an overall annual
rate of sudden death of 1 to 1.5 percent per year beyond BrUgada syndromE
infancy. The mechanism of sudden death is thought to be
ventricular arrhythmia in the majority and several triggers introduction
are recognised, including atrial arrhythmia, myocardial
ischemia and exercise.The most reliable predictor is a Brugada syndrome has increasingly been recognized worldwide
history of previous cardiac arrest. In patients without such as an important cause of SCD at a young age, in the absence of
a history, the most clinically useful markers of risk are a structural cardiac abnormalities. Patients affected with Brugada
family history of SCD, unexplained syncope unrelated to syndrome are at risk for SCD from fast polymorphic VT/
neurocardiogenic mechanisms, a flat or hypotensive response VF, especially at rest. Brugada syndrome is characterized by
of blood pressure to upright exercise, NSVT on ambulatory a typical ECG pattern consisting of ST segment elevation in
electrocardiographic monitoring or during exercise and the right precordial leads and in leads positioned in the upper
severe left ventricular hypertrophy on echocardiography intercostal spaces.82
defined as a maximal left ventricular wall thickness of 30 It is endemic in East and Southeast Asia, where it underlies
mm or more.78 Importantly, these markers of increased risk the sudden unexplained nocturnal death syndrome (SUNDS),
can all be identified non-invasively. Studies have shown that and is also particularly prevalent in Japan, Philippines and
patients with none of these features have a low risk of sudden Thailand, being the leading cause of sudden death among
death, less than 1 percent per year, whereas those with two young men.83 Arrhythmic events in Brugada syndrome
or more risk factors are at substantially higher risk of dying can occur at all ages, from childhood to the elderly (range
suddenly, with an estimated annual mortality rate of 3 percent 2–77 years), with a peak around the fourth decade, with
for those with two risk factors, rising to 6 percent in those higher disease prevalence in males (70–80% of all affected
with three or more risk factors. The evaluation of risk in subjects), particularly in regions where this syndrome is
these patients, therefore, has to be tailored to the individual, endemic, despite equal genetic transmission among both
taking into account the significance of the risk factor as well genders. However, in pediatric age, no sex predilection
as patient specific variables such as age. A particularly is seen. A role in gender disparity could be played by sex
malignant family history may be sufficient to trigger hormones.84 It is estimated that Brugada syndrome causes 4
primary preventative measures in the absence of a second to 12 percent of all SCD and up to 20 percent among patients
risk factor. Several studies have shown that obstruction of without identifiable structural abnormalities.The clinical
the left ventricular outflow tract is associated with increased presentation is heterogeneous and may include palpitations,
cardiovascular mortality, including sudden death. The dizziness syncope and (aborted) sudden death, but many
absolute risk of sudden death associated with obstruction subjects remain asymptomatic.85
in isolation is low, but it may represent an incremental risk The pathophysiological mechanism underlying this
factor in combination with other conventional markers. The syndrome and the typical ECG features and the genesis of the
extrapolation of data derived from adults may not always be arrhythmias:86
appropriate for children.79 Of the conventional markers of an 1. A repolarization disorder, i.e. unequal expression of the
increased risk for sudden death, unexplained syncope, severe transient outward potassium current Ito between the
left ventricular hypertrophy, and a family history of sudden epicardium and the other transmural layers87 or
death have been reported as being particularly relevant to 2. A depolarization disorder, i.e. a delay in the onset of the
young individuals.80,81 action potential in the region of the RVOT.88
In patients who are considered to be at high risk, insertion Three repolarization patterns of ST segment elevation
of an ICD should be regarded as the treatment of choice. In with two different shapes were recognized as potential
children, appropriate discharge rates are higher at 71 percent manifestations of Brugada syndrome.89 The coved-type
per year in those chosen for secondary prevention and 4 morphology (type I) is characterized by a cove-shaped J wave
percent per year in those having primary prevention. Despite elevation 2 mm, followed by a negative T wave. A type I
the life-saving benefits of ICDs, an increased incidence of ECG is required for the diagnosis, while a saddleback-shaped
complications has been reported in children compared with ST elevation or a coved-type lesser than 1 mm (types II–III)
adults, including a higher rate of inappropriate discharges are indeterminate forms that necessitate pharmacological
for supraventricular or sinus tachycardia, an increased risk challenge (Table 2 and Figure 11).
of infection, complications with leads related to growth and The diagnosis is posed when a type I ECG, spontaneously
the psychological sequels of appropriate and inappropriate or after provocation with sodium channel blockers, is present 863
discharges. Prior to the advent of ICDs, amiodarone was in more than one right precordial lead in the absence of
http://vip.persianss.ir
11 structural abnormalities and in association with one of the α subunit of the cardiac sodium channel protein and a linkage
following conditions: to a second locus on chromosome 3 was demonstrated in a
1. Documented VF or polymorphic VT large Brugada syndrome family and direct sequencing of
ElEctrophysiological issuEs in childrEn
2. A family history of SCD at a young age or a type I ECG in that region led very recently to the identification of a novel
family members mutation in the glycerol-3-phosphate dehydrogenase 1-like
3. Otherwise unexplained syncope gene (GPD1L).92
4. Inducibility of VT/VF with programmed electrical Sudden death results from fast polymorphic VT originating
stimulation. Patients with spontaneous Type I ECG are at from the RVOT, degenerating into VF. Ventricular arrhythmias
increased risk for malignant arrhythmias. and aborted sudden death in Brugada syndrome, occurs at
Brugada syndrome is inherited as an autosomal dominant rest when the vagal tone is augmented and often at night.
trait, linked to mutations in the SCN5A gene,91 encoding the Self-terminating VT may provoke recurrent syncope and
may explain why patients experience agonal respiration at
night after which they wake up, 80 percent of patients with
table 2 documented VT/VF have a history of syncope.
Diagnostic criteria for Brugada syndrome90
A central characteristic of Brugada syndrome is the absence
ST-segment abnormalities in leads V1-V3 of clear structural abnormalities. The ability to detect slight
Type 1 Type 2 Type 3 structural abnormalities has become greater with electron
J point ≥ 2 mm ≥ 2 mm ≥ 2 mm beam computed tomography (CT) scan and cardiac magnetic
T wave Negative Positive or Positive
resonance imaging (MRI).93,94 These methods have revealed
biphasic right ventricular (RV) wall motion abnormalities and RVOT
ST-T Coved type Saddleback Saddleback
enlargement. These findings demonstrate a link between
configuration functional and structural abnormalities and also support the
hypothesis that sodium channel mutations themselves may
ST segment Gradually Elevated Elevated
(terminal descending ≥ 1 mm < 1 mm induce subtle structural derangements and myocardial cell
portion) death.95
864
Figure 11: Different degrees of electrocardiographic changes seen in the same patient
differential diagnosis risk stratification 60
The conditions that are also accompanied by ST segment The prognosis of Brugada syndrome patients is still being
tachyarrhythmias
elevation should be carefully ruled out before the debated. While it is accepted that patients with aborted sudden
diagnosis of Brugada syndrome is made, which include death or those who have had symptoms such as dizziness,
arrhythmogenic right ventricular cardiomyopathy (ARVC), syncope or nocturnal agonal respiration should receive an
early repolarization syndrome, acute myocardial infarction, ICD, conflicting data exist regarding risk stratification and
isolated right ventricular infarction, Prinzmetal’s angina, therapeutic options in asymptomatic individuals.
electrolyte disturbances such as hyperkalemia and
hypercalcemia, acute pericarditis/myocarditis and ECG posTopEraTiVE TaChyCardia
recorded after electrical cardioversion (Box 1).
Drugs and intoxications can lead to a Brugada-like ST The principal patient groups include patients having had
segment elevation such as CCBs or nitrates, tricyclic or incisions over the atrium or ventricle. Atrial arrhythmias
tetracyclic antidepressant medications as well as selective are seen after incision over right atrium for simple cardiac
serotonin reuptake inhibitors and cocaine.96 repairs such as ASDs, VSDs, tetralogy of Fallot (TOF),
atrioventricular canal defects and related defects or following
Therapy complex surgeries such as Mustard or the Senning procedure
or the Fontan procedure. Ventricular tachycardia is seen in
The most effective prevention of sudden death in patients surgically corrected TOF and with related lesions such as
affected by Brugada syndrome who suffered from (aborted) certain types of double outlet right ventricle.99
cardiac arrest or syncope or are considered at high risk for
ventricular arrhythmias are ICDs.97 Quinidine is the only oral Ventricular Tachycardia in postoperative Tetralogy of fallot
agent that has been proven to normalize the ST segment and to
be effective in suppressing arrhythmic events in patients with Postoperatively, the most common congenital lesion associated
Brugada syndrome (both spontaneous events and inducible with VT is TOF, 10 to 15 percent have VT postoperatively.100
VT/VF during EPS);98 neither beta-blockers nor amiodarone Sudden death occurs in 5 to 10 percent. The risk factors associated
have proven to be effective. with the development of VT and sudden death include older age
at repair, a longer postoperative period, RV systolic pressure
greater than 60 mm Hg at rest, RV end-diastolic pressure greater
than 10 mm Hg at rest, depressed RV systolic function and
moderate to severe pulmonary or tricuspid regurgitation and
Box 1: abnormalities associated with Brugada-like st abnormal signal-averaged electrograms with late potentials and
segment elevation the development of VT. A wide QRS duration of greater than
Conditions that can lead to ST segment elevation, mimicking 180 ms has been associated with VT, correlated with severe
Brugada syndrome pulmonary insufficiency leading to RV dilation. QRS duration
• Early repolarization syndrome and degree of pulmonary regurgitation seem to be the greatest
• Cocaine intoxication risk factors for VT and sudden death.101,102 Valve replacement
• Acute myocardial infarction or isolated right ventricular decreases the incidence of episodes of VT and atrial flutter.The
• Infarction ventriculotomy, myocardial resection, and subsequent scarring
• Prinzmetal’s angina
provide the electrophysiological substrate of slow conduction
• Hyperkalemia and hypercalcemia
• Acute pericarditis/myocarditis and block that predisposes the patient to develop reentrant
• RBBB or LBBB and left ventricular hypertrophy arrhythmias. Ventricular arrhythmias occasionally occur despite
• Acute aortic dissection/acute pulmonary embolism good hemodynamic results, although sudden death occurs most
• Arrhythmogenic right ventricular cardiomyopathy commonly in VT associated with poor hemodynamics. Patients
• Long QT syndrome type III repaired earlier in life seem to have a lower incidence of VT,
• Hypothermia suggest that early repairs may decrease the incidence of VT in
• Duchenne muscular dystrophy these patients.
• Friedreich’s ataxia
• Various central and autonomic nervous system
abnormalities Evaluation
• Mechanical compression of the RVOT by a mediastinal
tumor All postoperative patients, especially those noted earlier at
LBBB =Left bundle branch block; RBBB = Right bundle
highest risk, should have periodic follow-up (usually yearly)
branch block, RVOT = Right ventriclular outflow tract. with standard ECGs. Holter monitoring should be performed
every 2 to 3 years in those without known arrhythmias and 865
http://vip.persianss.ir
11 every year in those in whom arrhythmias have been identified drug refractory cases. The ICD and pacemakers are valuable
and those treated for arrhythmias may need more frequent tools in the treatment of certain arrhythmias.
monitoring. Those with complex arrhythmias (NSVT,
ElEctrophysiological issuEs in childrEn
polymorphic PVCs or polymorphic VT) or monomorphic In nature there are neither rewards nor punishments - there
VT should undergo further testing, requiring an EPS. These are only consequences.
studies have been used to evaluate the propensity of these —Robert G. Ingersol
patients to develop VT, evaluate the efficacy of specific
pharmacologic therapies and locate the site of origin of the aCknoWlEdgmEnT
arrhythmia in patients who are candidates for ablative therapy.
Electrophysiological studies may be helpful in determining I wish to thank Dr Somasekhar for his help in preparing this
the need for implantation of an automatic cardioverter article.
defibrillator, negative study does not guarantee that VT/VF or
sudden death will not occur. rEfErEnCEs
866
14. Alboni P, Tomasi C, Menozzi C, et al. Efficacy and safety
of out-of-hospital self-administered single-dose oral drug
32. Kappenberger LJ, Fromer MA, Steinbrunn W, et al. Efficacy
of amiodarone in the Wolff-Parkinson-White syndrome with
60
treatment in the management of infrequent, well-tolerated rapid ventricular response via accessory pathway during atrial
tachyarrhythmias
paroxysmal supraventricular tachycardia. J Am Coll Cardiol. fibrillation. Am J Cardiol. 1984;54:330-5.
2001;37:548-53. 33. Drago F, Silvetti MS, Santis AD. Paroxysmal reciprocating
15. Wong KK, Potts JE, Etheridge SP, Sanatani S. Medications supraventricular tachycardia in infants: Electrophysiologically
used to manage supraventricular tachycardia in the infant: a guided medical treatment and long-term evolution of the re-
North American Survey. Pediatr Cardiol. 2006;27(2):199-203. entry circuit. Europace. 2008;10:629-35.
16. Tanel RE, Walsh EP, Lulu JA, Saul JP. Sotalol for refractory 34. Akhtar M, Jazayeri MR, Sra J, et al. Atrioventricular nodal
arrhythmias in pediatric and young adult patients: initial re-entry: clinical, electrophysiological, and therapeutic consid-
efficacy and long-term outcome. Am Heart J. 1995;130:791-7. erations. Circulation. 1993;88:282-95.
17. Blaufox AD. “Catheter Ablation of Tachyarrhythmias in Small 35. Lockwood D, Otomo K, Wang Z, et al. Electrophysiological
Children”. Indian Pacing and Electrophysiology Journal. characteristics of atrioventricular nodal reentrant tachycardia:
2005;5:51-62. implications for the reentrant circuit. In: Zipes DP, Jaliffe J
18. Munger TM, Packer DL, Hammill SC, et al. A population study (Eds). Cardiac Electrophysiology: From Cell to Bedside, 4th
of the natural history of Wolff-Parkinson-White syndrome edn. Philadelphia, WB Saunders. 2004, pp. 537-57.
in Olmsted County, Minnesota, 1953-1989. Circulation. 36. Clague JR, Dagres N, Kottkamp H, et al. Targeting the slow
1993;87:866-73. pathway for atrioventricular nodal reentrant tachycardia: Initial
19. Zipes, et al. Focal Atrial Tachycardia. ch 8.Clinical results and long-term follow-up in 379 consecutive patients.
Arrhythmology and Electrophysiology, 1st edn 2009, pp. 157- Eur Heart J. 2001;22:82.
76. Saunders, Elsevier, Philadelphia. 2009. pp.157-76. 37. Lindinger A, Heisel A, Von Bernuth G, et al. Permanent
20. Roberts KC, et al. Focal atrial tachycardia I: Clinical features junctional re-entry tachycardia: a multicenter long-term
diagnosis, mechanisms, and anatomic location. Pac and Clin follow-up study in infants, children and young adults. Eur
Electrophysiology. 2006;29:643. Heart J. 1998;19:936-42.
21. Kistler PM, Roderts KC, Haqanni HM, et al. P wave 38. Aquinaga L, Primo J, Anguera I, et al. Long-term follow-up in
morphology in focal atrial tachycardia: development of an patients with the permanent form of junctional reciprocating
algorithm to predict the anatomic site of origin. J Am Coll tachycardia treated with radiofrequency ablation. Pacing Clin
Cardiol. 2006;48:1010. Electrophysiol. 1998;21:2073-78.
22. Zeigler V, Gillette PC, Ross BA, et al.Flecainide for 39. Garson A Jr, Gillette PC. Junctional ectopic tachycardia in
supraventricular and ventricular arrhythmias in children and children: Electrocardiography, electrophysiology and pharma-
young adults. Am J Cardiol. 1989;14:185-91. cologic response. Am J Cardiol. 1979;44:298.
23. Colloridi V, Perri C, Ventriglia F, Critelli G. Oral sotalol in 40. Case CL, Gillette PC. Automatic atrial and junctional
pediatric atrial ectopic tachycardia. Am Heart J. 1992;123:254- tachycardias in the pediatric patient: Strategies for diagnosis
6. and management. Pacing Clin Electrophysiol. 1993;16:1323-
24. Walsh EP, Saul JP, Hulse JE, et al. Transcatheter ablation 35.
of ectopic atrial tachycardia in young patients using 41. Villain E, Vetter VL, Garcia JM, et al. Evolving concepts in the
radiofrequency current. Circulation. 1992;86:1138-46. management of junctional ectopic tachycardia: A multicenter
25. Santinelli V, Carlo Pappone, et al. Long-Term Prospective study. Circulation. 1990;81:1544.
Follow-Up Study of 184 Asymptomatic Children.The Natural 42. Rychik J, Marchlinski F, Sweeten TL, et al. Transcatheter
History of Asymptomatic Ventricular Pre-Excitation: A JACC. radiofrequency ablation of congenital junctional ectopic
2009;53:275-80. tachycardia in a neonate. Pediatr Cardiol. 1996;17:220-2.
26. Josephson ME. Preexcitation syndromes. In: Josephson ME 43. Balaji S, Sullivan I, Deanfield JE, James I. Moderate
(Ed). Clinical Cardiac Electrophysiology, 3rd edn. Philadelphia, hypothermia in the management of resistant automatic
Lippincott, Williams & Wilkins, 2002. pp. 322-424. tachycardias in children. Br Heart J. 1991;66:224.
27. Katsouras CS, Greakas GF, Goudevenos JA, et al. Localization 44. Alexander ME, Berul CI. Ventricular arrhythmias: When to
of accessory pathways by the electrogram. Pacing Clin worry. Pediatr Cardiol. 2000;21:532-41.
Electrophysiol. 2004;27:189. 45. Tsuji A, Nagashima M, Hasegawa S, et al. Long-term follow-
28. Arruda M, Wang X, McClennand J. ECG algorithm for up of idiopathic ventricular arrhythmias in otherwise normal
predicting sites of successful radiofrequency ablation of children. Jpn Circ J. 1995;59:654-62.
accessory pathways (abstract). Pacing Clin Electrophysiol. 46. Benson DW Jr, Gallagher JJ, Sterba R, et al. Catecholamine
1993;16:865. induced double tachycardia: Case report in a child. Pacing Clin
29. Fitzgerald DM, Hawthorne HR, Crossley GH, et al. P wave Electrophysiol. 1980;3:96-103.
morphology during atrial pacing along the atrioventricular 47. Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional
ring. ECG localization of the site of origin of retrograde atrial heart diseases, with prolongation of the QT interval and sudden
activation. J Electrocardiol. 1996;29:1. death. Am Heart J. 1957;54:59-68.
30. Epstein MC, Kiel EA, Victoria BE. Cardiac decompensation 48. Crotti L S-BM, Pedrazzini M, Ferrandi C, Insolia R, Goulene
following verapamil therapy in infants with supraventricular K, Salice P, Mannarino S, Schwartz PJ. Prevalence of the long
tachycardia. Pediatrics. 1985;75:737. QT syndrome. Circulation 2005;112(Suppl. II):660.
31. Kunze KP, Schluter M, Kuck KH. Sotalol in patients with 49. Garson A Jr, Macdonald D II, Fournier A, et al. The long QT
867
Wolff-Parkinson-White syndrome. Circulation. 1987;75: syndrome in children: An international study of 287 patients.
1050-7. Circulation. 1993;87:1866-72.
http://vip.persianss.ir
11 50. Scott WA, Macdonald DII. Two:one atrioventricular block in
infants with congenital long Q-T syndrome. Am J Cardiol.
catecholaminergic polymorphic ventricular tachycardia.
Circulation. 2004;110(Suppl. II):552.
1987;60:1409-10. 71. Priori SG, Napolitano C, Memmi M, et al. Clinical and
ElEctrophysiological issuEs in childrEn
51. Zareba W, Moss AJ, Schwartz PJ, et al. Influence of genotype molecular characterization of patients with catecholaminergic
on the clinical course of the long-QT syndrome. International polymorphic ventricular tachycardia. Circulation. 2002;106:
Long-QT Syndrome Registry Research Group. N Engl J Med. 69-74.
1998;339:960-5. 72. Sumitomo N, Harada K, Nagashima M, et al. Catecholaminer-
52. Garson A Jr. How to measure the QT interval—what is normal? gic polymorphic ventricular tachycardia: Electrocardiographic-
Am J Cardiol. 1993;72:14B-6B. characteristics and optimal therapeutic strategies to prevent
53. Schwartz PJ. Idiopathic long QT syndrome: progress and sudden death. Heart. 2003;89:66-70.
questions. Am Heart J. 1985;109:399-411. 73. De Rosa G, Delogu AB, Piastra M, et al. Catecholaminergic
54. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic polymorphic ventricular tachycardia: Successful emergency
criteria for the long QT syndrome: An update. Circulation. treatment with intravenous propranolol. Pediatr Emerg Care.
1993;88:782-4. 2004;20:175-7.
55. Vincent GM, Jaiswal D, Timothy KW. Effects of exercise on 74. Swan H, Laitinen P, Kontula K, et al. Calcium channel
heart rate, QT, QTc and QT/QS2 in the Romano-Ward inherited antagonism reduces exercise-induced ventricular arrhythmias
long QT syndrome. Am J Cardiol. 1991;68:498-503. in catecholaminergic polymorphic ventricular tachycardia
56. Swan H, Toivonen L, Viitasalo M. Rate daptation of QT patients with RyR2 mutations. J Cardiovasc Electrophysiol.
intervals during and after exercise in children with congenital 2005;16:162-6.
long QT syndrome. Eur Heart J. 1998;19:508-13. 75. Elliott P, Andersson B, Arbustini E, et al. Classification of the
57. Malfatto G, Beria G, Sala S, et al. Quantitative analysis of T cardiomyopathies: A position statement from the European
wave abnormalities and their prognostic implications in the Society of Cardiology Working Group on Myocardial and
idiopathic long QT syndrome. J Am Coll Cardiol. 1994;23:296- Pericardial Diseases. Eur Heart J. 2008;29:270-6.
301. 76. Nugent AW, Daubeneny PE, Chondros P, et al. The epidemiol-
58. Priori SG, Napolitano C, Diehl L, et al. Dispersion of QT ogy of childhood cardiomyopathy in Australia. N Engl J Med.
interval. A marker of therapeutic efficacy in the idiopathic long 2003;348:1639-46.
QT syndrome. Circulation. 1994;89:1681-8. 77. Lipshultz SE, Sleeper IA, Towbin JA, et al. The incident of
59. Ackerman MJ, Khositseth A, Tester DJ, Hejlik J, Shen WK, pediatric cardiomyopathy in two regions of the United States.
Porter CJ. Epinephrine-induced QT interval prolongation: N Engl J Med. 2003;348:1647-55.
A gene-specific paradoxical response in congenital long QT 78. McKenna WJ, England D, Doi YL, et al. Arrhythmias in
syndrome. Mayo Clin Proc. 2002;77:413-21. hypertrophic cardiomyopathy: Influence on prognosis. Br
60. Shimizu W, Noda T, Takaki H, et al. Epinephrine unmasks Heart J. 1981;46:168.
latent mutation carriers with LQT1 form of congenital long- 79. Fananapazir L, Chang AC, Epstein SE, McAreavey D. Prog-
QT syndrome. J Am Coll Cardiol. 2003;41:633-42. nostic determinants in hypertrophic cardiomyopathy: Pro-
61. Banai S, Tzivoni D. Drug therapy for torsade de pointes. J spective evaluation of a therapeutic strategy based on clini-
Cardiovasc Electrophysiol. 1993;4:206-10. cal, Holter, hemodynamic, and electrophysiological findings.
62. Crawford MH, Karliner JS, O’Rouke RA, et al. Prolonged Circulation. 1992;86:730-40.
QT interval syndrome: successful treatment with combined 80. McKenna WJ, Franklin RCG, Nihoyannopoulos P, et al.
ventricular pacing and propranolol. Chest. 1975;68:369. Arrhythmia and prognosis in infants, children and adolescents.
63. Moss AJ, Robinson J. Clinical features of the idiopathic long with hypertrophic cardiomyopathy. J Am Coll Cardiol.
QT syndrome. Circulation. 1992;85(suppl):I140-4. 1988;11: 147-53.217.
64. Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and 81. Yetman AT, Hamilton RM, Benson LN, McCrindle BW.
limitations of beta-blocker therapy in congenital long-QT Long-term outcome and prognostic determinants in children
syndrome. Circulation. 2000;101:616-23. with hypertrophic cardiomyopathy. J Am Coll Cardiol.
65. Moss AJ, Robinson J. Clinical features of the idiopathic long 1998;32:1943-50.
QT syndrome. Circulation. 1992;85(suppl):I140-4. 82. Sangwatanaroj S, Prechawat S, Sunsaneewitayakul B, et al.
66. Schwartz PJ, Locati EH, Moss AJ, et al. Left cardiac New electrocardiographic leads and the procainamide test
sympathetic denervation in the therapy of congenital long QT for the detection of the Brugada sign in sudden unexplained
syndrome. A worldwide report. Circulation. 1991;84:503-11. death syndrome survivors and their relatives. Eur Heart J.
67. Moss AJ, Liu JE, Gottlieb S, et al. Efficacy of permanent 2001;22:2290-6.
pacing in the management of high-risk patients with long QT 83. Matsuo K, Akahoshi M, Nakashima E, et al. The prevalence,
syndrome. Circulation. 1991;84:1524-9. incidence and prognostic value of the Brugada-type
68. Schwartz PJ, Priori SG, Brink PA, et al. Who Are the Long-QT electrocardiogram: A population-based study of four decades.
Syndrome Patients Who Receive an Implantable Cardioverter- J Am Coll Cardiol. 2001;38:765-70.
Defibrillator and What Happens to Them? Circulation. 84. Shimizu W, Matsuo K, Kokubo Y, et al. Sex hormone and
2010;122:1272-82. gender difference–role of testosterone on male predominance
69. Leenhardt A, Lucte V, Denjoy I, et al. Catecholaminergic in Brugada syndrome. J Cardiovasc Electrophysiol. 2007;18:
polymorphic ventricular tachycardia in children. A 7-year 415-21.
follow-up of 21 patients. Circulation. 1995;91:1512-9. 85. Hermida JS, Lemoine JL, Aoun FB, et al. Prevalence of the
868
70. Cerrone M, Colombi B, Bloise R, et al. Clinical and molecular Brugada syndrome in an apparently healthy population. Am J
characterization of a large cohort of patients affected with Cardiol. 2000;86:91-4.
86. Meregalli PG, Wilde AAM, Tan HL. Pathophysiological
mechanisms of Brugada syndrome: depolarization disorder,
95. Frustaci A, Priori SG, Pieroni M, et al. Cardiac histological
substrate in patients with clinical phenotype of Brugada
60
repolarization disorder or more? Cardiovasc Res. 2005;67: syndrome. Circulation. 2005;112:3680-7.
tachyarrhythmias
367-78. 96. Rouleau F, Asfar P, Boulet S, et al. Transient ST segment
87. Nabauer M, Beuckelmann DJ, Uberfuhr P, et al. Regional elevation in right precordial leads induced by psychotropic
differences in current density and rate dependent properties of the drugs: Relationship to the Brugada syndrome. J Cardiovasc
transient outward current in subepicardial and subendocardial Electrophysiol. 2001;12:61-5.
myocytes of human left ventricle. Circulation. 1996;93:168-77. 97. Brugada P, Brugada R, Brugada J, Geelen P. Use of the
88. Tukkie R, Sogaard P, Vleugels J, et al. Delay in right ventricular prophylactic implantable cardioverter defibrillator for
activation contributes to Brugada syndrome. Circulation. patients with normal hearts. Am J Cardiol. 1999;83:
2004;109:1272-7. 98D-100D.
89. Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed 98. Mizusawa Y, Sakurada H, Nishizaki M, Hiraoka M. Effects
diagnostic criteria for the Brugada syndrome: consensus report. of low-dose quinidine on ventricular tachyarrhythmias
Circulation. 2002;106:2514-9. in patients with Brugada syndrome: Low-dose quinidine
90. Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada therapy as an adjunctive treatment. J Cardiovasc Pharmacol.
R, Brugada P, et al. Proposed diagnostic criteria for the Brugada 2006;47:359-64.
syndrome: consensus report. Eur Heart J. 2002;23:1648-54. 99. Vetter VL, Horowitz LN. Electrophysiologic residua and
91. Chen Q, Kirsch GE, Zhang D, et al. Genetic basis and sequelae of surgery for congenital heart defects. Am J Cardiol.
molecular mechanism for idiopathic ventricular fibrillation. 1982;50:588.
Nature. 1998;392(6673):293-6. 100. Gillette PC, Yeoman MA, Mullins CE, et al. Sudden death after
92. Weiss R, Barmada MM, Nguyen T, Seibel JS, Cavlovich D, repair of tetralogy of Fallot. Circulation. 1977;56:566.
Kornblit CA, et al. Clinical and molecular heterogeneity in 101. Deanfield JE, McKenna WJ, Presbitero P, et al. Ventricular
the Brugada syndrome. A novel gene locus on chromosome 3. arrhythmia in unrepaired tetralogy of Fallot: Relation to
Circulation. 2002;105:707-13. age, timing of repair and hemodynamic status. Br Heart J.
93. Takagi M, Aihara N, Kuribayashi S, et al. Localized right 1984;52:77.
ventricular morphological abnormalities detected by electron- 102. Vaksmann G, Fournier A, Davignon A, et al. Frequency and
beam computed tomography represent arrhythmogenic prognosis of arrhythmias after operative “correction” of
substrates in patients with the Brugada syndrome. Eur Heart J. tetralogy of Fallot. Am J Cardiol. 1990;66:346-9.
2001;22:1032-41. 103. Stevenson WG, Delacretaz E, Friedman PL, Ellison KE.
94. Papavassiliu T, Wolpert C, Fluchter S, et al. Magnetic resonance Identification and ablation of macrore entrant ventricular
imaging findings in patients with Brugada syndrome. J tachycardia with the CARTO electroanatomical mapping
Cardiovasc Electrophysiol. 2004;15:1133-8. system. Pacing Clin Electrophysiol. 1998;21:1448-56.
869
http://vip.persianss.ir
C hapter
http://vip.persianss.ir
11 is typically not associated with structural CHD; is incessant; in smaller patients. The reported incidences of coronary
has a positive family history in 50 percent of cases; usually injury4,6 are 0.03 percent in children29 and 0.06 to 0.1 percent
does not respond to cooling; is associated with the maternal in adults30 during AVNRT and APs ablation. Cryoablation is
Electrophysiological Issues in Children
lupus anti-SSA and anti-SSB antibodies in some cases20 and a good alternative therapy in children with a 97 percent acute
may spontaneously resolve. Both JET types appear to be success rate and 2 percent recurrence with cryoablation.31
exacerbated by adrenergic stimulation,17 and respond well There are no reports of permanent AV block with cryoablation.
to intravenous amiodarone. JET may initially be best treated Accessory pathway function may spontaneously disappear
medically by minimizing adrenergic stimulation and starting by 1 year of age.32 Aggressive pharmacologic control should
amiodarone, particularly in infants because of potential risk be attempted first before ablation, because of known risks of
of AV block from either catheter21 or surgical17 ablation of catheterization and ablation in this age group. Radiofrequency
the JET focus (no clear site of ablation) in the AV junction. ablation lesions may increase in size during development and
Cryotherapy is the treatment of first choice for ablation. may lead to sudden cardiac death.3 Coronary artery damage is
Permanent form of junctional reciprocating tachycardia also a heightened risk in infants due to close proximity of the
is caused by an orthodromic reciprocating tachycardia coronaries (RCA and LCX) to the ablation catheter.4-6 Despite
involving a slow and decremental retrogradely conducting these, ablation is still needed in a small subset of infants with
concealed AP. It may resolve spontaneously.22 Catheter AP-mediated tachycardia. Lesion size is related to catheter-tip
ablation is highly effective technique in difficult to control size, RF power, tip temperature and lesion duration. Therefore
patients with PJRT, with minimal risk for AV block.23,24 Most ablation should be done on atrial side with low temperature
common site of these APs is posteroseptal, but may occur in (55°C–60°C) and of shorter duration burns with 5F catheter
any location along the AV groove. Electrogram characteristics, tip. Cryotherapy is much less harmful to coronary arteries.
electrophysiologic techniques and mapping techniques are The pre-excitation syndromes are statistically increased
somewhat different for PJRT pathways than for typical non- in patients with Ebstein malformation, l-transposition of
decremental APs. It is often impossible to confirm an AP the great arteries or hypertrophic cardiomyopathy. Multiple
as the retrograde conduction pathway using the standard pathways are present in 30 to 80 percent of patients33-37
technique of His refractory ventricular premature beat compared with 5 to 10 percent of patients without CHD.30,34,36
because the retrograde conduction decrements after premature Accessory atrioventricular connections in Ebstein
ventricular stimulation. The VA interval is usually long and anomaly pose special problems. Differentiation of atrial
an AP potential may be present in as many as 75 percent of and ventricular signals and precise localization of the AV
cases.25 The pathways must usually be mapped and ablated in groove can be difficult in Ebstein anomaly, leading to a
tachycardia, because it is often not possible to achieve reliable lack of specificity for what appear to be excellent signals
exclusive AP conduction during ventricular pacing, owing to in predicting a successful ablation site. The true AV groove
either AV node conduction or retrograde block at any cycle (site of AP potentials) is best identified by a right coronary
length longer than that of the tachycardia. Success rate of electrode wire. Catheter stabilization for free wall pathways in
radiofrequency ablation (RFA) is more than 95 percent, but the largest hearts is difficult and is not sufficiently improved
recurrence rates are higher than for typical APs. AV block and through the use of a long sheath or a variety of approaches.2
coronary damage are the potential complications.4 Coronary damage is common, probably because of the thin
Dual AV node physiology in pediatric patients is seen right ventricular wall and often diminutive right coronary
in only 60 percent of cases26,27 in comparison to adults artery. The success rate is 80 to 90 percent with infrequent
(90–100%)28 with inducible AVNRT. The difference in the major complications such as permanent AV block.33-35
baseline conduction properties of the two pathways does not Recurrence rates have been reported to be as high as 40
reach the threshold for dual physiology in about 40 percent of percent, particularly, if multiple pathways are present.33-37
children. Magnitude of the AH (atrium-His bundle) change at Ablation procedures in patients with heterotaxy or
the transition from the fast to the slow pathway is related to AV discordance require detailed echocardiography and
heart size and therefore to age, because AH or the PR interval angiography for defining the complex anatomy of the atria, the
increases with age. Younger children have faster conduction in AV ring and the coronary sinus. Careful attention must be given
the slow pathway than older children and adults.27 In children, to locate the normal conduction system thereafter. In most of
the slope change of AH versus AA (atrium-atrium) is a more the patients with AV discordance, the AP has been associated
reliable and specific measure of the transition between the fast with the tricuspid valve, whereas the His bundle has been
and slow pathways than the AH jump alone. For ablation of associated more closely with the mitral valve. After locating
AVNRT, smaller catheter should be used in smaller children the normal and abnormal conduction, electrophysiologic study
(< 20 kg), to minimize the lesion size. Success rate is more and RFA of the APs can proceed with less risk for damage
than 95 percent.26 The risk for heart block is higher because to the normal conduction system. The AV node in corrected
of relatively large lesion size compared with the size of the transposition is typically situated superior and anterior in the
872 heart and closeness of ‘smaller’ AV node to the slow pathway atrial wall. The penetrating bundle then runs in the fibrous
continuity between the right sided mitral valve and the anterior in animals, children or adults. Isolated case reports of late 61
cusp of the posterior great artery and continues as left bundle coronary stenosis have also been described, especially in
branch on the right side of the ventricular septum. The right children who had extensive ablation of transannular pathways
http://vip.persianss.ir
11 of Cardiolgoy/American Heart Association (ACC/AHA) Vessel recanalisation with balloon dilatation should be
guidelines:43 considered in case of severe obstruction or occlusion of the
1. Congenital abnormalities of the conduction system. subclavian vein or the superior vena cava combined with
Electrophysiological Issues in Children
2. Acquired heart blocks after cardiac surgery for correction surgical treatment before planning an epicardial or alternative
of congenital defects. approach.
3. Sinus node diseases. Epicardial pacing indications in newborns or infants are:
Rare indications include the therapy of tachyarrhythmias, 1. Too small baby.
hypertrophic obstructive cardiomyopathy and of the long- 2. Venous abnormalities or congenital malformations, which
QT-syndrome. make a venous lead implantation impossible: discordant
atrioventricular connection, tricuspid atresia or after
Implantation Fontan surgery.
3. If all upper venous vessels have thrombotic occlusions and
Implantation of a pacemaker in infants requires the individual alternative approaches are not possible.
assessment of: 4. If a right-to-left shunt with the risk of systemic embolization
1. Access (endovenous versus epicardial). exists.
2. Leads. 5. If one wants to prevent the endovenous problems regarding
3. Implantation site (infraclavicular versus abdominal). growth. Epicardial leads (cork-screw mechanism or only
4. Selection between subcutaneous versus submuscular plane. a suture fixed) should be steroid-eluting and bipolar.
The expected growth of the child, lifelong dependency Disadvantage of epicardial pacing leads are higher
on pacing therapy and multiple revisions in future have to be threshold and slightly higher fracture rate because of the
taken into consideration during implantation. higher mechanical stress compared to endovenous leads.
Currently it is recommended to use the epicardial approach Another alternative for endocardial pacing is the transatrial
in infants until the age of 3 to 4 years in order to prevent a approach. Indications for this more invasive approach are
lesion of the subclavian vein. With advancement in technique occluded, obstructed, hypoplastic central veins or disconnected
and hardwares, the trend from epicardial towards endovenous superior vena cava from the RA (either congenital or post
leads is increasing. surgical). A transatrial approach can replace the epicardial
Lead revision due to growth of children remains a potential stimulation, which would normally be used in these situations
problem in pacing therapy until puberty. Fibrotic attachment and prevents its potential complications.
to the vessel wall (mostly at the junction of the subclavian Pulse generators are usually implanted subpectorally (sub
and brachiocephalic vein with the superior vena cava) can muscularly) to prevent pocket related problems in small
compromise a later advancement of the lead. This results in children. This requires bipolar leads to prevent pectoral muscle
implantation of an additional new lead in a relatively short stimulation. The cosmetic aspect is much more favorable
period of time after the first implantation despite the normal with this approach. It also prevents Twiddler syndrome. For
lead parameters. Keeping the large loop in the RA to reduce using epicardial systems (mostly in babies), pocket is created
this increases the chances of displacement (due to tension abdominally behind the anterior sheet of the rectus muscle
of the floating loop on the tip of the endocardial electrode), (subxiphoidal approach).
arrhythmias (if migrating to right ventricle) and significant In view of multiple lead implantations during lifetime,
pulmonary valve insufficiency (if migrating to pulmonary pediatric pacing therapy should only be carried out by
artery). Every year approximately 10 millimeters of lead length experienced surgeons and in well equipped cath labs to prevent
is necessary to compensate body growth, thus 80 millimeter or to minimize complications. Prior to every single lead
right atrial lead loop allows 6 to 12 years (mean 8 years) of insertion, physician should judge the central venous access in
growth without need of lead replacement.44 Redundant lead terms of stenosis or occlusion sonographically and then try to
loop within the inferior vena cava or sliding technique of lead plan the operation. If a new pacing lead has to be implanted
fixation at the site of venous entrance with slowly absorbable endovenously, the old screw-in lead should be extracted
sutures are of questionable value in view of lead adherence to during the same session. An additional endovenous lead
vascular wall. loop for further growth has to be considered preoperatively.
The isodiametric construction of leads allows an easier and The latest rate adaptive pacemakers should be implanted to
safer elective extraction. Active fixation allows an anchorage provide most physiological pacing mode.
at every desired position, which is helpful in anatomic Left ventricular systolic or diastolic dysfunction can
variations or complex cardiac malformations. Continuous result after long-term right ventricular apical pacing in
release of steroid in the first phase after implantation ensures the young. This can be reduced by pacing at septal or
stable low chronic stimulation thresholds. Severe tricuspid high right ventricular outflow tract. With these positions,
regurgitation and atrial or ventricular perforation are the echocardiographic findings show markedly normalized
874 potential complications after lead placement. ventricular contraction patterns.
The implantable cardioverter-defibrillator (ICD) is now 4. Blaufox AD, Saul JP. Acute coronary artery stenosis during
slow pathway ablation for atrioventricular nodal re-entrant
61
established as safe and effective for preventing sudden cardiac
death (SCD) in children. The continued miniaturization of tachycardia in a child. J Cardiovasc Electrophysiol. 2004;15:
http://vip.persianss.ir
11 20. Dubin AM, Cuneo B, Strasburger J, et al. Congenital junctional
tachycardia and congenital complete AV block: a shared
33. Levine JC, Walsh EP, Saul JP. Radiofrequency ablation of
accessory pathways associated with congenital heart disease
etiology? Heart Rhythm. 2005;2:313-5. including heterotaxy syndrome. Am J Cardiol. 1993;72:689-93.
Electrophysiological Issues in Children
21. Gillette PC, Garson A Jr, Porter CJ, et al. Junctional automatic 34. Jackman WM, Wang XZ, Friday KJ, et al. Catheter ablation of
ectopic tachycardia: New proposed treatment by transcatheter accessory atrioventricular pathways (Wolff-Parkinson-White
His bundle ablation. Am Heart J. 1983;106:619-23. syndrome) by radiofrequency current [see comments]. N Engl
22. Guarnieri T, German LD, Gallagher JJ. The long RP’ tachycar- J Med. 1991;324:1605-11.
dias [review]. Pacing Clin Electrophysiol. 1987;10: 103-17. 35. Van Hare GF, Lesh MD, Stanger P. Radiofrequency catheter
23. Ticho BS, Walsh EP, Saul JP. Ablation of permanent junctional ablation of supraventricular arrhythmias in patients with
reciprocating tachycardia. In: Huang SK, (Ed). Radiofrequency congenital heart disease: results and technical considerations. J
Catheter Ablation of Cardiac Arrhythmias: Basic Concepts and Am Coll Cardiol. 1993;22:883-90.
Clinical Applications. Mt. Kisko, NY: Futura; 1994. pp. 397- 36. Smith WM, Gallagher JJ, Kerr CR, et al. The electrophysiologic
409. basis and management of symptomatic recurrent tachycardia in
24. Gaita F, Haïssaguerre M, Giustetto C, et al. Catheter ablation patients with Ebstein’s anomaly of the tricuspid valve. Am J
of permanent junctional reciprocating tachycardia with Cardiol. 1982;49:1223-34.
radiofrequency current. J Am Coll Cardiol. 1995;25:648-54. 37. Twidale N, Wang X, Beckman KJ, et al. Factors associated
25. Haïssaguerre M, Montserrat P, Warin JF, et al. Catheter with recurrence of accessory pathway conduction after
ablation of left posteroseptal accessory pathways and of long radiofrequency catheter ablation. Pacing Clin Electrophysiol.
RP’ tachycardias with a right endocardial approach. Eur Heart 1991;14:2042-8.
J. 1991;12:845-59. 38. Symons JC, Shinebourne EA, Joseph MC, et al. Criss-cross
26. Van Hare GF, Chiesa NA, Campbell RM, et al. Pediatric heart with congenitally corrected transposition: Report of a
Electrophysiology Society. Atrioventricular nodal reentrant case with d-transposed aorta and ventricular preexcitation. Eur
tachycardia in children: effect of slow pathway ablation on fast J Cardiol. 1977;5:493.
pathway function [comment]. J Cardiovasc Electrophysiol. 39. Dunnigan A, Benson DW, Benditt DG. Atrial flutter in
2002;13:203-9. infancy: diagnosis, clinical features and treatment. Pediatrics.
27. Blaufox AD, Rhodes JF, Fishberger SB. Age related changes 1985;75:725-9.
in dual AV nodal physiology. Pacing Clin Electrophysiol. 40. Kugler JD, Danford DA, Houston K, et al. Radiofrequency
2000;23:477-80. catheter ablation for paroxysmal supraventricular tachycardia
28. Rosen KM, Bauernfeind RA, Swiryn S, et al. Dual AV nodal in children and adolescents without structural heart disease.
pathways and AV nodal reentrant paroxysmal tachycardia. Am Pediatric EP Society, Radiofrequency Catheter Ablation
Heart J. 1981;101:691-5. Registry. Am J Cardiol. 1997;80:1438-43.
29. Kugler JD, Danford DA, Deal BJ, et al. Radiofrequency 41. Perry JC, Garson A, Jr. Supraventricular tachycardia due
catheter ablation for tachyarrhythmias in children and to Wolff-Parkinson-White syndrome in children: early
adolescents. The Pediatric Electrophysiology Society. N Engl J disappearance and late recurrence [see comments]. J Am Coll
Med. 1994;330:1481-7. Cardiol. 1990;16:1215-20.
30. Calkins H, Langberg J, Sousa J, et al. Radiofrequency catheter 42. Bink-Boelkens MTHE. Cardiac pacing in infants and children.
ablation of accessory atrioventricular connections in 250 Neth J Cardiol 1992;5:199-202.
patients: abbreviated therapeutic approach to Wolff-Parkinson- 43. Recommendations for Permanent Pacing in Children,
White syndrome. Circulation. 1992;85:1337-46. Adolescents and Patients With Congenital Heart Disease-
31. Avari JN, Jay KS, Rhee EK. Experience and results during ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy
transition from radiofrequency ablation to cryoablation of Cardiac Rhythm Abnormalities: Executive Summary: A
for treatment of pediatric atrioventricular nodal reentrant Report of the American College of Cardiology/American Heart
tachycardia. Pacing Clin Electrophysiol. 2008;31:454-60. Association Task Force on Practice Guidelines.
32. Deal BJ, Keane JF, Gillette PC, et al. Wolff-Parkinson-White 44. Gheissari A, Hordof AJ, Spotnitz HM. Transvenous pacemaker
syndrome and supraventricular tachycardia during infancy: in children: relation of lead length to anticipated growth. Ann
management and follow-up. J Am Coll Cardiol. 1985;5:130-5. Thorac Surg. 1991;52:118-21.
876
Sec t i on
12
Miscellaneous
http://vip.persianss.ir
C hapter
http://vip.persianss.ir
12
Miscellaneous
Figure 1: Aortic root angiogram and cardiac MRI demonstrating normal coronary arrangement
atrioventricular groove. A number of marginal branches, the branch of the right coronary artery, although as previously
largest of which is termed the obtuse marginal, arise along mentioned, in the rest the conal artery takes origin directly from
the course of the circumflex and supply the lateral wall of the aortic root with a separate ostial orifice. The next branch
the left ventricle and the anterolateral papillary muscle. The is usually the sinus node artery, although again in around 50
sinus node artery arises from the circumflex in 50 percent of percent this originates from the circumflex. Several marginal
individuals. Around 10 percent of the population display a branches, the largest of which is termed the acute marginal,
‘left-dominant’ pattern,3 where the posterior descending (also supply the right ventricular free wall. Around 90 percent of the
termed the inferior interventricular)7 artery arises from the population have a ‘right-dominant’ pattern, with the posterior
circumflex and proceeds to supply the atrioventricular node descending artery originating from the right coronary artery.3
and inferior right ventricular surface. In these individuals, the It is important to note that the term ‘dominance’ is merely a
circumflex artery is considerably larger in diameter. descriptive term reflecting this pattern and does not refer to
The left anterior descending (LAD) artery descends along the coronary artery supplying the majority of the myocardium,
the anterior surface of the heart in the anterior interventricular which is nearly always the left coronary artery, irrespective
groove and can continue beyond the apex to anastamose with of the origin of the posterior descending artery. The posterior
the posterior descending artery. The left conal artery is the first descending artery supplies the inferior surface of the left and
branch and may form the circle of Vieussens by anastomosing right ventricles, has posterior septal perforators that penetrate
with the right conal artery.8 Diagonal branches supply the the interventricular septum and also has a branch supplying
anterior surface of the left and right ventricles and around the atrioventricular node.
four septal perforators enter the interventricular septum
and anastamose with septal branches from the posterior Physiology
descending artery.
The coronary arteries are responsible for the supply of oxygen
Right Coronary Artery to the highly aerobic myocardium. This supply is determined
by the oxygen content of the blood (which is primarily
Originates from the right sinus of Valsalva and initially courses related to amount of saturated hemoglobin) and the amount
anteriorly between the pulmonary trunk and right atrial of coronary flow, which in turn is determined by coronary
appendage to the right atrioventricular groove. In around 50 perfusion pressure (the difference between the coronary artery
880 percent of the population the right conal artery forms the first pressure and ventricular end diastolic pressure) and coronary
arterial vascular resistance. During ventricular systole, Abnormalities 62
the myocardial compressive forces cause almost complete
obstruction of the arterioles, resulting in an extremely high
Classification
http://vip.persianss.ir
12 Box 1: Classification of coronary anomalies from Angelini15
Cx = Circumflex; LAD = Left descending coronary artery; LCA = Left coronary artery; RCA = Right coronary artery; PD = Posterior descending branch.
882
shunted into the pulmonary artery, further aggravating the is around 30 years of age, although for patients surviving 62
ischemia. Stenosis of the origin of the left coronary artery may beyond 50, the risk of sudden death appears to decline.17
at this point reduce the degree of ‘steal’ and confer a degree of
Figure 2: Twelve-lead ECG in a 6-week-old patient with ALCAPA. Note the pathological Q waves 883
and T wave inversion in I, aVL and V4-6, along with ST elevation in V2-3
http://vip.persianss.ir
12 present in myocarditis and dilated cardiomyopathy. The
presence of a Q wave width > 30 milliseconds in lead I, Q
wave depth > 3 mm in aVL and QR pattern in aVL has been
Miscellaneous
ECHO
The left ventricle is typically dilated with severely impaired
systolic and diastolic function, although left ventricular
function can remain normal in infants with persistent elevation
in the pulmonary artery pressures25 and up to 10 percent of
adult patients may have normal global left ventricular function,
but often abnormalities are detected on strain imaging or stress
echocardiography.17,26 In contrast to dilated cardiomyopathy,
Figure 4: Echocardiogram in parasternal short axis clearly demon-
the papillary muscles tend to be bright and echogenic as a strating the connection of the left coronary artery to the pulmonary
result of infarction and fibrosis, although this is non-specific artery on 2D, with retrograde flow from the coronary artery into the
(Figure 3). There is often significant mitral regurgitation pulmonary artery, noted on color flow mapping
(MR) (from annular dilation, papillary muscle shortening and
also possible papillary muscle rupture) and the left atrium
is dilated. Advances in echocardiographic technology and and occasionally collateral flow can be seen. In cases where
resolution now means that it is technically feasible to confirm the diagnosis remains uncertain following echocardiography,
the diagnosis with 2D imaging of the coronary arteries, with more definitive imaging is required.
the left coronary artery demonstrated originating from the
pulmonary artery (Figure 4), but as the left coronary artery often CT/MRI
takes a course very close to the left aortic sinus, the connection
can easily be misinterpreted as normal (in as many as 70% in Improved spatial resolution of cardiac computed tomography
some reports).24 Doppler assessment with color flow mapping (CT) and magnetic resonance (MRI) imaging has led to their
of the coronary flow is therefore essential for both confirming increasing use in coronary assessment and a number of reports
and excluding the diagnosis with abnormal retrograde flow confirm accurate diagnosis of ALCAPA particularly in the adult
noted in the left coronary artery and a retrograde jet of flow population where acoustic windows for echocardiography
noted in the pulmonary artery.27 The right coronary artery tend to be poor.17,29-31 The CT demonstrates better spatial
tends to be dilated (with an RCA: aortic ratio often ≥ 0.14)28 resolution, although MRI allows for functional assessment of
the left ventricle and myocardium (including late enhancement
to assess myocardial viability) and does not involve ionizing
radiation. The high heart rates and high spatial resolution
required to clearly identify the coronary arteries in infants
limits the usefulness of these techniques in younger patients,
although it is likely that improving technology will extend
their use into this population.
Cardiac Catheterization
Remains the gold standard for diagnosis, although with
improved imaging techniques catheterization is no longer
routinely necessary20 and invasive assessment in small
and often critically ill patients carries inherent risk. On
hemodynamic assessment the left ventricular end diastolic
pressure tends to be severely elevated with a consequent
increase in the pulmonary artery and right ventricular
pressures. Left to right shunts at the level of the pulmonary
Figure 3: 2-D Echocardiogram from the apical four-chamber view artery tend to be small and may not be identified on a
in a patient with ALCAPA. The left ventricle is dilated, with severely
saturation run, but this is rarely required with diagnostic
884 impaired ventricular function and in particular note the highly echogenic
appearance of the papillary muscles secondary to ischemic fibrosis. angiography. Either root angiography or selective right
A left atrial line is also seen crossing the atrial septum coronary angiography should clearly delineate the anomalous
62
left coronary artery and degree of collateralization (Figures in adults, reduced vessel elasticity, increased friability and
5A and B). excessive collateralization make direct reimplantation more
hazardous and internal mammary artery bypass grafting may
Management be safer,39,40 There is, however, little data on long-term patency
of internal mammary grafts in ALCAPA patients and direct
Supportive medical management including ventilation, reimplantation is still advocated in the majority of patients.41
inotropes, afterload reduction and diuretics can be used to If bypass grafting is performed, it is recommended that the
stabilise a sick patient, but the key to management is urgent left coronary origin is ligated to prevent graft thrombosis from
surgical repair to improve myocardial perfusion. Early surgical competitive flow.
techniques prior to the introduction of cardiopulmonary bypass Overall mortality rates have fallen from 75 percent to 80
aimed to reduce pulmonary artery steal by either increasing percent in the early 1980s to 0 percent to 23 percent in the
proximal pulmonary artery pressures with pulmonary artery current era,20 with most mortality in the immediate post-
banding32 or ligating the pulmonary origin of the anomalous operative period. Risk factors identified for 30 day mortality
left coronary artery.33 Subsequently establishment of a two- include young age at operation and reduced pre-operative left
coronary system was reported with saphenous vein grafting34 ventricular function, with the degree of MR not consistently
or direct anastomosis of the left subclavian artery to the left found to influence early mortality.42-44 The degree of MR tends
coronary artery.35 Direct reimplantation of the left coronary to improve with time and there is generally a consensus that
artery was first reported in 197436 and with growing expertise concomitant mitral valve surgery at the time of ALCPA repair
in neonatal coronary surgery as a result of the arterial switch is not necessary (unless there is papillary muscle rupture).
operation, has become established as the procedure of choice This also increases cardiopulmonary bypass time in an already
in the majority. It is technically feasible in most patients and compromised and ischemic ventricle.20,42-44 Mechanical
affords high long-term patency rates.37 If the position or length circulatory support may be required in the immediate
of the left coronary artery makes direct transfer unfeasible, postoperative period to bridge to recovery and it is mandatory
creation of an intrapulmonary coronary baffle (Takeuchi that this is available to units performing surgical repair.
operation)38 is an alternative to direct coronary transfer, but Mid- to long-term results following repair are excellent
future interventions for complications such as suprapulmonary with steady improvement and often normalization in left
stenosis, baffle leaks and aortic regurgitation are required ventricular function within 1 to 2 years and low long-term
in up to 30 percent of patients.20 It has been suggested that mortality.20,43-46 Medical therapy to help off-load the ventricle 885
http://vip.persianss.ir
12 is often required for a period of time following repair. As
previously mentioned, additional surgery to repair the mitral
valve is usually not necessary unless there has been rupture of
Miscellaneous
887
Figure 7: The right coronary artery is noted to take origin from a high position of the left aortic sinus on this cardiac MRI
http://vip.persianss.ir
12 As with ALCAPA, patients can present in infancy with critical Abnormalities of Coronary Termination
myocardial ischemia, although interestingly and perhaps due
to the lack of pulmonary artery ‘steal’ a much larger proportion Coronary Artery Fistulae
Miscellaneous
Management
Treatment decisions depend on the age of the patient, size of
fistula and degree of symptoms. Clearly large fistulae resulting in
cardiac failure unresponsive to medical management in infancy Figure 9: Cardiac MRI in the same patient as Figure 8 confirming
require intervention. However, symptoms of congestive cardiac the proximal right coronary artery dilation and fistula connecting to the
failure in infancy may respond to medical therapy in which case right atrium
889
or intracardiac closure on cardiopulmonary bypass was is no coronary supply to the myocardium distal to the point
the mainstay of treatment until the first reported catheter of occlusion. If uncertain, this can be tested by observing
occlusion in 1983.81 Since then percutaneous interventional the ECG during temporary balloon occlusion of the fistula
occlusion has gradually become the procedure of choice in the (Figures 10A to D). Results following device occlusion have
vast majority of patients. Reports exist with devices ranging been comparable to surgical results with an expected mortality
from detachable balloons, coils, vascular plugs, patent ductus of < 1 percent. Complications such as device embolisation,
A B
C D
890 Figures 10A to D: Catheter occlusion of coronary artery fistula. In panel A the large fistula is delineated on angiography from the right coronary
artery connecting to the right atrium, with the normal coronary artery seen descending at 6 o’clock. In Panel B the fistula has been occluded with
a wedge catheter and injection of contrast proximally further delineates the right coronary artery and confirms no important myocardial supply
distal to the occlusion. Lateral (Panel C) and AP (Panel D) projections following occlusion of the fistula with a Amplatzer muscular ventricular
septal defect occluder
ST changes and coronary occlusion have been reported, matter of ingrowth or outgrowth? Anatomy and Embryology.
1989;180(5):437-41.
62
but are uncommon and small residual shunts appear to be
present in around 10 percent of patients, which is similar to 11. Reese DE, Mikawa T, Bader DM. Development of the coronary
http://vip.persianss.ir
12 28. Koike K, Musewe NN, Smallhorn JF, et al. Distinguishing be-
tween anomalous origin of the left coronary artery from the
with special attention to the mitral valve. Eur J Cardiothorac
Surg. 2009;36(2):244-8.
pulmonary trunk and dilated cardiomyopathy: role of echocar- 45. Schwartz ML, Jonas RA, Colan SD. Anomalous origin of
Miscellaneous
diographic measurement of the right coronary artery diameter. left coronary artery from pulmonary artery: recovery of left
British Heart Journal. 1989;61:192-7. ventricular function after dual coronary repair. J Am Coll
29. Castorina S, Mignosa C, Degno S, et al. Demonstration of an Cardiol. 1997;1997:547-53.
anomalous connection between the left coronary artery and 46. Ojala T, Salminen J, Happonen JM, et al. Excellent functional
the pulmonary artery using a multislice CT 64. Clin Anat. result in children after correction of anomalous origin of left
2008;21(4):319-24. coronary artery from the pulmonary artery—a population-
30. Komocsi A, Simor T, Toth L, et al. Magnetic resonance studies based complete follow-up study. Interact Cardiovasc Thorac
in management of adult cases with Bland-White-Garland Surg. 2010;10(1):70-5.
syndrome. Int J Cardiol. 2007;123(1):e8-11. 47. Williams IA, Gersony WM, Hellenbrand WE. Anomalous right
31. Greer ML, Mondal TK, Yoo SJ. Late presentation of anomalous coronary artery arising from the pulmonary artery: a report of 7
origin of the left coronary artery from the pulmonary artery: the cases and a review of the literature. Am Heart J. 2006;152(5):
definitive role of cardiovascular magnetic resonance imaging. 1004-17.
Cardiol Young. 2011;21(2):225-6. 48. Alexi-Meskishvili V, Dahnert I, Hetzer R, et al. Origin of
32. Case RB, Morrow AG, Stainsby W, et al. Anomalous origin of the circumflex coronary artery from the pulmonary artery in
the left coronary artery. Circulation. 1958;17:1062-8. infants. Ann Thorac Surg. 1998;66(4):1406-9.
33. Sabiston DC, Neil CA, Taussig HB. The direction of blood flow 49. Ochoa-Ramirez E, Valdez-Garza HE, Reyes-Gonzalez R, et al.
in anomalous left coronary artery arising from the pulmonary Double anomalous coronary origin from the pumonary artery:
artery. Circulation. 1960;22:591-7. successful surgical correction in an infant. Tex Heart Inst J.
34. Cooley DA, Hallman GL, Bloodwell RD. Definitive surgical 2005;32(3):348-50.
treatment of anomalous origin of the left coronary artery from 50. Said SM, Dearani JA, Burkhart HM, Schaff HV. Surgical
pulmonary artery: indications and results. J Thorac Cardiovasc management of congenital coronary arterial anomalies in
Surg. 1966;52:798-808. adults.Cardiol Young 2010;20(Suppl. 3):68-85.
35. Meyer BW, Stefanik G, Stiles QR, et al. A method of definitive 51. Roberts WC, Shirani J. The four subtypes of anomalous origin
surgical treatment of anomalous origin of the left coronary of the left main coronary artery from the right aortic sinus
artery. A case report. J Thorac Cardiovasc Surg. 1968;56: (or from the right coronary artery). Am J Cardiol. 1992;70(1):
104-7. 119-21.
36. Neches WH, Mathews RA, Park SC, et al. Anomalous origin 52. Basso C, Maron BJ, Corrado D, et al. Clinical profile of con-
of the left coronary artery from the pulmonary artery. A new genital coronary artery anomalies with origin from the wrong
method of surgical repair. Circulation. 1974;50:582-7. aortic sinus leading to sudden death in young competitive
37. Vouhe PR, Tamisier D, Sidi D, et al. Anomalous left coronary athletes. J Am Coll Cardiol. 2000;35(6):1493-501.
artery from the pulmonary artery: results of isolated aortic 53. Liberthson RR. Sudden death from cardiac causes in children
reimplantation. Ann Thorac Surg. 1992;54:621-7. and young adults. N Engl J Med. 1996;334:1039-44.
38. Takeuchi S, Imamura H, Katsumoto K, et al. New surgical 54. Moustafa SE, Zehr K, Mookadam M, et al. Anomalous
method for repair of anomalous left coronary artery from interarterial left coronary artery: an evidence based systematic
pulmonary artery. J Thorac Cardiovasc Surg. 1979;78:7-11. overview. Int J Cardiol. 2008;126(1):13-20.
39. Kitamura S, Kawachi K, Nishii T, et al. Internal thoracic artery 55. Alphonso N, Anagnostopoulos PV, Nolke L, et al.
grafting for congenital coronary malformations. Ann Thorac Anomalous coronary artery from the wrong sinus of
Surg. 1992;53:513-6. Valsalva: a physiologic repair strategy. Ann Thorac Surg.
40. Chan RK, Hare DL, Buxton BF. Anomalous left main coronary 2007;83(4):1472-6.
artery arising from the pulmonary artery in an adult: treatment 56. Soon KH, Chaitowitz I, Selvanayagam JB, et al. Comparison
by internal mammary artery grafting. J Thorac Cardiovasc of fluoroscopic coronary angiography and multislice coronary
Surg. 1995;109:393-4. angiography in the characterization of anomalous coronary
41. Kottayil BP, Jayakumar K, Dharan BS, et al. Anomalous origin artery. Int J Cardiol. 2008;130(1):96-8.
of left coronary artery from pulmonary artery in older children 57. Post JC, van Rossum AC, Bronzwaer JGF, et al. Magnetic
and adults: direct aortic implantation. Ann Thorac Surg. resonance angiography of anomalous coronary arteries: a new
2011;91(2):549-53. gold standard for delineating the proximal course? Circulation.
42. Lange R, Vogt M, Horer J, et al. Long-term results of repair 1995;92:3163-71.
of anomalous origin of the left coronary artery from the 58. Gulati R, Reddy VM, Culbertson C, et al. Surgical management
pulmonary artery. Ann Thorac Surg. 2007;83(4):1463-71. of coronary artery arising from the wrong coronary sinus, using
43. Brown JW, Ruzmetov M, Parent JJ, et al. Does the degree standard and novel approaches. J ThoracCardiovascSurg.
of preoperative mitral regurgitation predict survival 2007;134(5):1171-8.
or the need for mitral valve repair or replacement in 59. Davies JE, Burkhart HM, Dearani JA, et al. Surgical manage
patients with anomalous origin of the left coronary artery ment of anomalous aortic origin of a coronary artery. Ann
from the pulmonary artery? J Thorac Cardiovasc Surg. ThoracSurg. 2009;88(3):844-7.
2008;136(3):743-8. 60. Duran AC, Angelini A, Frescura C, et al. Anomalous origin of
44. Ali WB, Metton O, Roubertie F, et al. Anomalous origin of the right coronary artery from the left aortic sinus and sudden
892
the left coronary artery from the pulmonary artery: late results infant death. Int J Cardiol. 1994;45(2):147-9.
61. Liberman L, Pass RH, Kaufman S, et al. Left coronary artery
arising from the non-coronary sinus: a rare congenital coronary
72. Latson L. Coronary artery fistulas: how to manage them.
Catheter CardiovascInterv. 1997;70:110-16.
62
anomaly. Pediatr Cardiol. 2005;26(5):672-4. 73. Levin DC, Fellows KE, Abrams HL. Hemodynamically
893
http://vip.persianss.ir
C hapter
Left atrial Left ventricular inflow Dyspnea, paroxysmal nocturnal dyspnea, Myxoma
obstruction orthopnea, syncope, sudden cardiac death Fibroma
(SCD) (may have postural variation) Undifferentiated
especially myxomas sarcoma
Osteosarcoma
Embolism—central nervous Stroke, myocardial infarction (MI)
system, coronary,
peripheral, retinal
Right atrium Benign superior vena cava Right heart failure, i.e. peripheral Myxoma
syndrome (obstruction) edema, ascites
Right ventricle Right ventricular inflow and Dyspnea, appropriate murmurs, Fibroma
outflow obstruction syncope
Commonly observed symptoms and signs include dyspnea, angiosarcomas are the commonest malignant primary tumors
orthopnea, paroxysmal nocturnal dyspnea, pulmonary edema, and have a predilection to arise in the RA. Tumors arising in
cough, hemoptysis, edema and fatigue. Symptoms may be the RA grow into the atrial lumen and obstruct blood flow,
worse in certain body positions in mobile pedunculated producing hemodynamic changes that are similar to those seen
tumors as in the left atrial myxoma. Respiratory symptoms with triscuspid stenosis/regurgitation. Typical cardiovascular
due to pulmonary venous hypertension that worsen rather than signs and symptoms are those of right heart failure (i.e. fatigue,
improve in the upright position are a clue to the diagnosis of peripheral edema, hepatomegaly, ascites and prominent ‘a
this tumor. The characteristics of the clinical findings vary waves’ in the jugular veins). On physical examination, a
on repeat examinations. On physical examination along diastolic murmur along with the ‘tumor plop’ may be heard.
with the diastolic murmur, a characteristic ‘tumor plop’ Occasionally patients present with recurrent arrhythmias. In
may be heard in early diastole (only in 15% of the cases). A addition to obstructing circulation through the right side of the
fixed tumor does not produce a positional alteration in signs heart, tumor fragments may be released into the pulmonary
and symptoms. The patients along with clinical features of circulation, causing symptoms consistent with pulmonary
pulmonary venous hypertension often have a history of atrial embolism. Right atrial hypertension can result in shunting of
arrhythmia. In addition to interfering with the circulation, left venous blood into the systemic circulation if a patent foramen
atrial tumors may release tumor fragments or thrombi into the ovale is present, resulting in hypoxemia or systemic emboli.
systemic circulation. The most serious complications of such
embolization are neurologic. Right Ventricular Tumors
Right Atrial Tumors Tumors arising in the right ventricle (RV) can be mis-
diagnosed as pulmonic stenosis, restrictive cardiomyopathy 895
Similar to left atrial tumors, myxomas are the most common or tricuspid regurgitation. Lesions arising in the RV may
tumors of the right atrium (RA). Sarcomas and in particular, result in right-sided heart failure or right ventricular outflow
http://vip.persianss.ir
12 obstruction leading to shortness of breath, syncope and sudden Table 3
death. Prevalence of primary cardiac tumors
Miscellaneous
Pericardial Tumors
Benign pericardial tumors are rare and account for one-fourth
of the benign tumors of the heart. Among the reported cases
are teratomas, fibromas, lipomas, pericardial cysts, etc. Many
are discovered because of a chance X-ray demonstration of
an unusual heart contour. In others, sudden appearance of
symptoms is due to hemorrhagic pericardial effusion. This
occurs in both benign and malignant pericardial tumors.
However, the latter have a more rapid course, are more
often associated with chest pain or dry cough and are often A B
associated with pulmonary metastasis.
The histological classification of cardiac tumors and their
prevalence are enumerated in Table 3 with details of the more
common tumors in the paragraphs that follow:5
Cardiac Myxomas
Myxoma is the most common benign cardiac tumor and is
usually located in the LA (75%). Other sites include RA (18%),
left ventricle (LV) (4%) and the RV (4%). The involvement of
more than one site can occur in 5 percent cases.6 C
Histologically, these tumors are composed of scattered Figures 1A to C: A. Solid, polypoidal, smooth-surfaced mass lesion
cells within a mucopolysaccharide stroma (Figures 1A to C). attached to the inter-atrial septum on left atrial aspect; B. Cut surface
The cells originate from a multipotent mesenchyme that is shows myxoid, greenish yellow appearance with foci of hemorrhage;
C. Stellate to spindle shaped cells in myxoid background. Note
capable of neural and endothelial differentiation. Myxomas perivascular arrangement of cells (H&E x 400). Courtesy: Dr Pradeep
896 produce vascular endothelial growth factor (VEGF) which Vaideeswar
probably contributes to the induction of angiogenesis and the occur due to the release of vasoactive substances including 63
early stages of tumor growth. interleukin-6. Hemolytic anemia is associated with calcified
Macroscopically, typical myxomas are pedunculated and myxomas in a right atrial location.
A B C
Figures 2A to C: A. Apical four-chamber view shows a large right atrial myxoma obstructing the tricuspid valve with a pedicle attached to
inter-atrial septum (IAS); B. Left atrial myoxma obstructing the mitral valve; C. Contrast enchanced computer tomography (CT) showing
moderate sized lobular soft tissue density mass lesion in the body of left atrium with epicenter at IAS—classical appearance of myxoma. Ao
= Aorta; LA = Left atrium; LV = Left ventricle; M = Mass; RA = Right atrium; RV = Right ventricle. CT image courtesy: Dr Madhav Hegde Dr 897
Madhav Hegde
http://vip.persianss.ir
12 Treatment and Prognosis signal intensity of lipomas on T1-weighed images on MRI
shows the superior diagnostic ability of this modality. For the
Once a presumptive diagnosis of myxoma has been made on atrial arrhythmias, medical management with antiarrhythmics
Miscellaneous
imaging studies, prompt resection for complete removal of the should be given, but if the patient fails to respond , surgical
myxoma is required because of the risk of embolization or resection is indicated. Because of the symptoms they cause
cardiovascular complications, including sudden death. The atrial and their progressive growth, myocardial lipomas usually
septum to which the myxoma is attached should be excised and require resection.
if this is a substantial portion of the septum, a Dacron patch Lipomatous hypertrophy of the IAS is an exaggerated
is used for the repair. This leads to normalization of serum growth of non-encapsulated normal fat existing within the
interleukin-6 levels and resolution of constitutional symptoms septum at the level of fossa ovalis and is not a true tumor.12
and the intracranial aneurysms may regress and resolve. Cardiac The septal hypertrophy is greater than 2 cm in thickness
transplantation has been reported for other tumors and might be (normal < 1 cm) and is seen primarily in older patients and
considered for multiple recurrent atrial myxomas. in those who are obese. In the absence of symptoms of atrial
Postoperative recovery is generally rapid. However, atrial arrhythmias or heart block, they do not require resection. It is
arrhythmias or AV conduction abnormalities were present often necessary to differentiate lipomatous hypertrophy of the
postoperatively in 26 percent of patients in one series. In IAS from lipomas. This is often seen in obese elderly people
addition, patients are at risk for recurrence of the myxoma, and a TEE is required to show the hour glass septum with fatty
which may occur in 2 to