Peripheral Vascular Interventions

Editors:
Kandarpa, Krishna
Title: Peripheral Vascular Interventions, 1st Edition
Copyright 2008 Lippincott Williams & Wilkins
2008
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Library of Congress Cataloging-in-Publication Data
Peripheral vascular interventions / edited by Krishna Kandarpa.
p.; cm.
Includes bibliographical references and index.
ISBN-13: 978-0-7817-8687-4
ISBN-10: 0-7817-8687-8
1. Peripheral vascular diseasesDiagnosis. 2. Peripheral vascular diseasesImaging. 3.
Peripheral vascular diseasesSurgery. I. Kandarpa, Krishna.
[DNLM: 1. Peripheral Vascular Diseasesdiagnosis. 2. Diagnostic Imagingmethods. 3.
Diagnostic Techniques, Cardiovascular. 4. Peripheral Vascular Diseasessurgery. 5.
Radiography, Interventional. WG 500 P447 2007]
RC694.P488 2007
616.131dc22
2007031804
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Editors: Kandarpa, Krishna
> Front of Book > Editors
Editor
Krishna Kandarpa MD, PhD
Professor and Chairman
Department of Radiology
The University of Massachusetts Medical School
Worcester, Massachusetts
CONTRIBUTING AUTHORS P.vii
Hani Abujudeh MD
Assistant Professor of Radiology
Harvard Medical School
Massachusetts General Hospital
Boston, Massachusetts
Michael A. Bettmann MD
Professor of Radiology
Wake Forest University
Baptist Medial Center
Winston-Salem, North Carolina
Patrick Chevallier MD
Universit de Nice
Nice, France
Mark A. Creager MD
Professor of Medicine
Department of Medicine
Director, Vascular Center
Brigham and Women's Hospital
Michael D. Dake MD
Internal Medicine
Chairman, Department of Radiology
Harrison Medical Teaching Professor of Radiology
University of Virginia Health System
Charlottesville, Virginia
Steven Deitelzweig MD
Ochsner Clinic Foundation
New Orleans, Louisiana
Joyoni Dey PhD

Instructor
Hale Ersoy MD
Instructor
Department of Cardiovascular Imaging
Shigeru Furui MD
Professor and Chairman of Radiology
Teikyo University
Itabashi-Ku, Tokyo, Japan
Klaus D. Hagspiel MD
Chief, Division of Noninvasive Cardiovascular Imaging
Anne Hamik MD, PhD

Assistant Professor
Division of Cardiovascular Medicine
Case Western Reserve University
Cleveland, Ohio
Ziv J. Haskal MD
Professor of Radiology and Surgery
Columbia University College of Physicians and Surgeons
Director, Division of Vascular & Interventional Radiology
Columbia University Medical Center/New York Presbyterian Hospital
New York, New York
Shozo Hirota MD, PhD

Hyogo College of Medicine
Nishinomiya City, Japan
Hanno Hoppe MD
Clinical Fellow
Dotter International Institute
Oregon Health & Science University
Portland, Oregon
Michael R. Jaff DO
Associate Professor of Medicine
Director of Cardiovascular Medicine
The Massachusetts General Hospital
Priya Jagia MD, DNB

Assistant Professor
Department of Cardiovascular Radiology
All India Institute of Medical Sciences
New Delhi, India
Ashu Jhamb MBBS

The Alfred Hospital
Melbourne, Australia

Professor and Chairman
John A. Kaufman MD
Professor of Radiology Chief
Dotter Interventional Institute
Oregon Health Sciences University
Portland, Oregon
Neil M. Khilnani MD
Associate Professor of Radiology
Weill Medical College of Cornell University
New York Presbyterian Hospital
New York, New York
Gi-Young Ko MD, PhD

Asan Medical Center
University of Ulsan College of Medicine
Seoul, Korea
Kaoru Kobayashi MD
Pascal Lacombe MD
Hopital Ambroise Par
Universit Paris Ouest Versailles Saint Quentin
Boulogne cedex, France
Daniel A. Leung MD
Associate Professor
Section Chief, Vascular & Interventional Radiology
Medical College of Virginia
Richmond, Virginia
Martin J. Lipton MD
Cardiovascular Imaging Section
Stuart Lyon MB, BS

The Alfred Hospital
Lindsay Machan MD
Professor
University of British Columbia Hospital
Vancouver, B.C. Canada
Hiroaki Maeda MD
Todd E. Markowitz MD
Division of Interventional Radiology
Peter Y. Milne MB. BS

Vascular Surgery Unit
The Royal Melbourne Hospital
Robert J. Min MD, MBA

Acting Chairman and Associate Professor of Radiology
New York, New York
Norio Nakao MD
Meena Narayanswamy MBBS, MD

Radiologist
Axcess Medicine
Global DoctorsMalaysia
Kuala Lumpur, Malaysia
Jae Hyung Park MD

Professor
Seoul National University College of Medicine
Seoul, Korea
Jean-Pierre Pelage MD, PhD

Hopital Ambroise Par
Universit Paris Ouest Versailles Saint Quentin
Boulogne cedex, France
David A. Phillips MD
Associate Professor and Director of Radiology
Jeffrey S. Pollak MD
Co-Section Chief, Vascular and Interventional Radiology
Yale University School of Medicine
New Haven, Connecticut
Martin R. Prince MD, PhD

Columbia College of Physicians and Surgeons
New York, New York
Mahmood K. Razavi MD
Director
Center for Clinical Trials
St. Joseph Vascular Institute
Orange, California
Eric Reiner DO
Assistant Professor of Diagnostic Radiology
Joshua L. Rosebrook MD
Clinical Fellow
Cardiovascular Imaging Section
Frank J. Rybicki MD, PhD

Director
Applied Imaging Science
Sanjiv Sharma MBBS, MD

Professor and Director
Cardiothoracic Radiology
All India Institute of Medical Sciences
New Delhi, India
Thomas A. Shin MD
Harneil Singh Sidhu MD

Interventional Radiology Fellow
University of Virginia
Ajay K. Singh MD
Assistant Professor
University of Massachusetts Memorial Medical Center
Bob H. Smouse MD
University of Illinois College of Medicine
Peoria, Illinois
Thomas A. Sos MD
Cornell University
New York, New York
Kyu Bo Sung MD
Asan Medical Center
Seoul, Korea
James L. Swischuk MD
Clinical Associate Professor of Radiology
University of Illinois College of Medicine
Codirector, Interventional Radiology
OSF Saint Francis Medical Center
Peoria, Illinois
Malcolm K. Sydnor MD
Assistant Professor
Vascular & Interventional Radiology
Medical College of Virginia at Virginia Commonwealth University
Richmond, Virginia
Kenneth R. Thomson MD
Monash University
Clayton, Victoria
The Alfred Hospital
David W. Trost MD
Associate Professor of Radiology
Cornell University
New York, New York
Renan Uflacker MD
Medical University of South Carolina
Charleston, South Carolina
Christopher Vargo MD
Cross Sectional Fellow
Johns Hopkins University School of Medicine
Baltimore, Maryland
Ajay K. Wakhloo MD, PhD

Neurological Surgery and Neurology
Chief Division, Neuroimaging and Intervention
Program Director, Neuroradiology
University of Massachusetts Medical School
Robert I. White Jr. MD

Director of Yale Vascular Malformation Center
Section of Vascular and Interventional Radiology
Satoshi Yamamoto MD
> Front of Book > Preface
Preface
Endoluminal techniques for treating vascular lesions have revolutionized modern medicine by
reducing procedural morbidity and by showing outcomes better than, or at least equal to, those
with invasive surgery. Having their origins in interventional radiology, these minimally invasive
methods are now employed by other specialists, who generally limit their use to arterial
atherosclerotic occlusive or aneurysmal disease. Radiologists, on the other hand, have
continued to pioneer new applications beyond the systemic arterial beds and have vastly
widened the use of endovascular techniques. Peripheral Vascular Interventions is a
compendium of both traditional and innovative endovascular interventions.
In organizing this book, I approached experts with wide experience in a particular vascular
problem. As a result, because specific problems are more prevalent in certain geographic
locations, the expertise varied also by geography, and so the book acquired a highly scholarly
as well as a uniquely international flavor. I thank each and every one of my generous colleagues
from around the world for sharing their knowledge and time to help create this book, which
would not have been realized without their expert contributions.
The contents are organized into three sections, which cover the clinicopathological aspects of
the spectrum of peripheral vascular diseases, report state-of-the-art vascular imaging
modalities, and provide in-depth descriptions of endovascular treatment approaches to a variety
of vascular problems. Each chapter addresses the epidemiology and the etiology of the
disease, the clinical and laboratory evaluation, and the role of preprocedure imaging. The roles
of conventional medical and surgical treatment alternatives are discussed where appropriate.
Peripheral Vascular Interventions is intended for anyone with an interest in vascular diseases
and interventions. It will serve as a reference, covering a wide variety of applications while
recognizing that some readers may rarely perform certain procedures. Importantly, since
imaging is central to the evaluation of many of these disease states, several chapters address
modern imaging modalities, their relevant physics, optimal techniques, and appropriate clinical
use. The chapters dedicated to procedures address relevant clinical issues, indications, patient
selection, procedural and technical considerations, results, and postprocedural management.
Where appropriate, available endovascular devices are described.
As with most such large undertakings, it is difficult to recognize and thank everyone who was
involved in the production of this book. I do, however, wish to thank all of the contributors and
editors at Lippincott Williams & Wilkins, specifically Kerry Barrett and Lisa McAllister, for their
support and patience throughout the process. I also wish to thank Brenda Vigneaux, my
assistant, and Kathy Delongchamp for their help.
> Table of Contents > Section I - Peripheral Vascular Diseases > Chapter 1 - Peripheral Arterial Diseases
Chapter 1
Peripheral Arterial Diseases
Anne Hamik
Mark A. Creager
In the broadest context, peripheral arterial diseases (PADs) encompass stenotic, occlusive, and
aneurysmal diseases of the aorta and its noncoronary branch arteries. Most peripheral arterial
diseases are caused by, or associated with, atherosclerosis and can be grouped under the
general rubric, atherosclerotic peripheral vascular disease (APVD). These include PAD of the
lower and upper extremities, aortic aneurysm, renal and mesenteric artery occlusive disease,
and carotid artery disease. Atherosclerotic disease of the coronary arteries, while sharing risk
factors and pathobiology with APVD, by definition is not peripheral and is not discussed in this
chapter. This chapter reviews the epidemiology, etiology, clinical presentation, evaluation, and
medical management of APVD. The chapter also reviews acute arterial occlusion caused by
thrombosis or embolism. Other, less common, causes of PAD, such as degenerative or
entrapment disorders, are beyond the scope of this chapter. Subsequent chapters will address
revascularization strategies.
PATHOBIOLOGY OF PERIPHERAL ARTERIAL DISEASES

Atherosclerosis
Contrary to the original concept of atherosclerosis, atheromas are not merely inert collections
of lipids (1,2). In fact, an active inflammatory mechanism has a fundamental role in all stages of
atherosclerotic disease, from initiation through progressive development of stenotic plaques,
and, ultimately, in the complications of atherothrombosis leading to plaque rupture, erosion,
superimposed thrombosis, and clinical sequelae such as myocardial infarction, stroke, and
symptomatic APVD. Knowledge of the cellular and molecular events underlying atherosclerosis
has been derived from both clinical and basic arenas. This confluence of information has
provided evidence of a well-defined sequence of molecular events that lead from a healthy
endothelium to vascular stenosis and atherothrombosis, which cause clinical disease (Fig. 1-1).
Endothelial dysfunction is the critical first step in the pathobiology of atherosclerosis.
Dysfunctional endothelium is characterized by a decrease in the expression or availability of
anti-inflammatory and antithrombotic mediators including nitric oxide, thrombomodulin, and
plasminogen activator inhibitor-1. Biochemical signals (e.g., increased humoral inflammatory
cytokines) and biomechanical changes (e.g., loss of laminar shear stress) contribute to the loss
of vascular homeostasis. These changes lead to expression of cell adhesion molecules such as
vascular cell adhesion molecule-1 (3,4), E-selectin, and P-selectin (5,6) and the subsequent
recruitment into the subendothelium of those leukocytes found in early atheroma, namely,
monocytes and T cells (7). These cells are responsible for the perpetuation of this local
inflammatory response via production of monocyte and T cell chemoattractants (8, 9, 10) and
growth factors such as macrophage colony stimulating factor (F) (11) that contribute to the
differentiation of monocytes into macrophages and eventually foam cells. Further elaboration of
pro-inflammatory signaling molecules such as -interferon and tumor necrosis factor- leads to
activation of endothelial cells, macrophages, and smooth muscle cells (SMCs) (12). Resultant
chemical mediators drive SMC replication and apoptosis, create angiogenic signals that lead to
the creation of plaque-associated microvessels, and contribute to the abundant extracellular
matrix that comprises the developing plaque (13).
Progression of atheroma appears to be a discontinuous process caused by episodes of
physical disruption of the plaque with subsequent exposure of flowing blood to potent
procoagulants residing in the plaque (including tissue factor, von Willebrand factor, and
collagen). This triggers thrombosis and expansion of the lesions (2,14). Three types of
disruption have been identified: superficial erosion (15), disruption of the microvessels within the
plaque (16), and fracture of the fibrous cap (17). The production by activated plaque-
associated macrophages of the proteolytic enzymes matrix metalloproteinases contributes to
the third mechanism via degradation of the fibrous plaque cap (18). Repeated episodes of
plaque disruption and thrombosis/fibrosis are a critical part of the transition from a fatty lesion
to a fibrous, stenotic atherosclerotic lesion.
Although the molecular steps of atheroma progression have been well defined, both by
experimental models using genetically modified mice and by correlative information derived from
extracts from human lesions, the triggers of inflammation are not as well established (2).
Proposed triggers include oxidized lipoproteins and dyslipidemia (especially very low-density
lipoprotein [LDL] particles (19,20). Similarly, the modified macromolecules found in the diabetic
state (advanced glycation end products) can augment the inflammatory process (21).
Hypertension is a risk factor for atherosclerosis, and angiotensin II, in addition to its
vasoconstrictor effects, is pro-inflammatory (22,23). Finally, infection may fuel the inflammation
of atherosclerosis (24,25). However, the potential contribution of infectious agents to
atherosclerosis has not been consistently supported by epidemiological or prospective studies.
The natural history of atherosclerosis is that of a progressive disease. Clinical events are the
result of atheroma progression leading to flow-limiting stenosis, plaque rupture resulting in
sudden occlusive thrombosis, or artery-to-artery embolism. Stenosis of the arteries supplying
the lower extremity leads to ischemia with exercise or at rest, stenosis of the renal arteries to
renal dysfunction and hypertension, and stenosis of the mesenteric arteries to intestinal
ischemia and the associated symptoms of postprandial pain and weight loss. Occlusive
thrombosis consequent to plaque rupture (occlusive atherothrombosis) causes acute symptoms
that vary according to the vascular bed affected and include myocardial infarction, stroke, and
acute limb or organ ischemia. Atheroemboli composed of disrupted, loosened plaque, and
adherent thrombus travel with the flowing blood and are the frequent culprits in artery-to-artery
embolism, leading to ischemic stroke and acute ischemia of limbs or the mesentery. Showers of
cholesterol crystals derived from plaque cause diffuse small- and mediumvessel ischemia;
clinical manifestations may include fever, myalgias, blue toe syndrome, and renal dysfunction.
FIGURE 1-1. Schematic of the evolution of the atherosclerotic plaque. (1) Accumulation of
lipoprotein particles in the intima. The modification of these lipoproteins is depicted by the
darker color. Modifications include oxidation and glycation. (2) Oxidative stress including
products found in modified lipoproteins can induce local cytokine elaboration. (3) The
cytokines thus induce increased expression of adhesion molecules for leukocytes that
cause their attachment and chemoattractant molecules that direct their migration into the
intima. (4) Blood monocytes, upon entering the artery wall in response to chemoattractant
cytokines such as monocyte chemoattractant protein 1 (MCP-1), encounter stimuli such as
macrophage colony stimulating factor (M-CSF) that can augment their expression of
scavenger receptors. (5) Scavenger receptors mediate the uptake of modified lipoprotein
particles and promote the development of foam cells. Macrophage foam cells are a source
of mediators such as further cytokines and effector molecules such as hypochlorous acid,
superoxide anion (O2-), and matrix metalloproteinases. (6) Smooth muscle cells in the
intima divide and other smooth muscle cells migrate into the intima from the media. (7)
Smooth muscle cells can then divide and elaborate extracellular matrix, promoting
extracellular matrix accumulation in the growing atherosclerotic plaque. In this manner, the
fatty streak can evolve into a fibrofatty lesion. (8) In later stages, calcification can occur
(not depicted) and fibrosis continues, sometimes accompanied by smooth muscle cell
death (including programmed cell death, or apoptosis), yielding a relatively acellular fibrous
capsule surrounding a lipid-rich core that may also contain dying or dead cells and their
detritus. LDL, low-density lipoprotein; IL-1, interleukin-1. (Reprinted from Heart Disease, A
Textbook of Cardiovascular Medicine, 6th edition. The Vascular Biology of
Atherosclerosis, plate 18, 2001, with permission from Elsevier.) (See the color insert.)
Arterial Thrombosis
Arterial thrombosis may occur as a complication of atherosclerotic disease following rupture of
the fibrous cap of an atherosclerotic plaque. Arterial thrombosis may also develop in patients
with thrombophilia or result from injury or dissection and in the presence of foreign materials
such as synthetic vascular grafts or intra-aortic balloon pumps. Acquired thrombophilic
conditions that are associated with arterial thrombosis include cancer, inflammatory bowel
disease, heparin-induced thrombocytopenia, thrombocythemia, polycythemia vera, and
antiphospholipid antibodies. In contrast to venous thrombotic disorders, where genetic markers
of thrombophilia have been clearly established (Factor V Leiden, prothrombin gene mutation,
antithrombin III, protein C and protein S deficiencies, etc.), most studies show no demonstrable
relationship of these markers for arterial thrombosis (26), with the possible exception of
elevated fibrinogen (27,28) and von Willebrand factor levels (29). However, several small
studies have suggested that combinations of genetic variants plus an acquired factor may
increase risk, that is, Factor V Leiden plus cigarette smoking (30,31) or Factor V Leiden plus
homocystinemia (32). Homozygous homocystinuria increases risk for arterial thrombosis (33),
and thrombosis may occur in the absence of any of the other clinical manifestations of the
disease (mental retardation, ectopia lentis, and skeletal abnormalities) (34). Increased risk is
proposed to be secondary to homocysteine-induced vascular intimal damage (35,36). Oral
contraceptives may increase the risk of stroke (37) and are contraindicated in women with a
history of arterial thrombotic events (38). Acute graft occlusion is the most common etiology of
acute lower extremity ischemia in many centers (39). The factors associated with graft failure
include technical issues such as retained valve cusps, strictures, intimal hyperplasia, and
atherosclerosis.
Acute occlusion of peripheral arteries is also caused by thromboembolism originating from the
heart, a proximal aneurysm or bypass graft, or by atheroembolism. Atheroembolism is an
arterio-arterial embolism originating from an atherosclerotic plaque. Embolization of thrombus
leads to occlusion of medium-sized to large distal arteries anywhere in the arterial system.
Embolization of cholesterol crystals occludes small to medium-sized arteries, often affecting the
skin, lower extremities (blue toe syndrome), and kidneys.
Fibromuscular Dysplasia
FMD is a noninflammatory, nonatherosclerotic process that may cause PAD (40). This
angiopathy is usually due to malformation of arterial structure and is characterized by
fibroplasia, most often of the tunica media (80% to 95% of cases), but can involve the intima or
adventitia (41,42). Hyperplasia of fibrous or muscular components of the wall results in either
concentric hypertrophy or protrusion of ridges of tissue into the lumen and can cause severe
stenosis. FMD is most often found in young Caucasian women but can occur at any age, in
both genders and in other races. The etiology of FMD is not fully understood, but estrogen
exposure, mechanical and ischemic factors, cigarette smoke, and autoantibodies have been
implicated (43). Many cases are familial and demonstrate an autosomal dominant transmission
with variable penetrance. Clinical manifestations relate to the vascular bed involved. The renal
arteries are affected in 75% of cases, and stenosis from FMD is the most common cause of
renovascular hypertension in children and young adults (44). When FMD involves the internal
carotid arteries, the stenosis can result in cerebral ischemia or thromboembolism and stroke.
LOWER EXTREMITY ATHEROSCLEROTIC PERIPHERAL

ARTERIAL DISEASE
Etiology
Lower extremity PAD is defined by the presence of atheroma in the medium and large vessels
of the lower extremities, and is the result of the pathological processes described above.
Established atherosclerotic risk factors increase the risk for lower extremity PAD (Fig. 1-2).
Cigarette smoking is a more potent risk factor for lower extremity PAD than it is for
atherosclerotic disease of other vascular beds, including the coronary arteries (45). Diabetes is
strongly associated with lower extremity PAD, and outcomes are frequently worse in the
presence of diabetes than in nondiabetic persons with PAD. Diabetic persons with lower
extremity PAD are five times more likely to undergo amputation (46). Dyslipidemia also
increases the risk for development of lower extremity PAD. High total cholesterol and low high-
density lipoprotein cholesterol are associated with increased risk of PAD, however, multivariate
analysis has not supported a role for triglycerides (47). Although the relative risk of
hypertension is modest in most studies (1.3- to 2.2-fold), the high prevalence of hypertension in
the older population make it a significant factor in the development of lower extremity PAD (47).
FIGURE 1-2. Risk of developing lower extremity PAD. The range for each risk factor is
estimated from epidemiological studies. The relative risks take into consideration current
smokers versus former smokers and nonsmokers, presence versus absence of diabetes
and hypertension, and highest versus lowest quartile of homocysteine and C-reactive
protein. The estimate for hypercholesterolemia is based on a 10% risk for each 10 mg/dL
rise in total cholesterol. (Adapted from Dormandy JA, Rutherford RB, for the TransAtlantic
Inter-Society Consensus [TASC] Working Group. Management of peripheral arterial
disease [PAD]. J Vasc Surg. 31:S1-S296. 2000, with permission from The Society for
Vascular Surgery.)
Epidemiology
Epidemiological studies suggest that 8 to 12 million people in the United States have lower
extremity PAD (48,49). The mechanism used to detect disease influences estimates of
prevalence and incidence. Most epidemiologic studies use the ankle-brachial index (ABI) to
assess the prevalence of PAD, because, symptomatic disease underrepresents PAD.
Asymptomatic PAD is two- to sevenfold more prevalent than symptomatic PAD (50). The
prevalence of PAD as defined by ABI (described below) rises steeply with age: <5% before
age 50, ~10% by age 65, and >25% in patients 80 years of age (47). In populations with risk
factors for PAD such as diabetes or cigarette smoking, the prevalence is even higher,
approximating 30% (51, 52, 53, 54). Blacks may have a higher rate of disease than non-
Hispanic whites, for reasons that are not yet known (55). A male predominance of PAD based
on ABI is not established, with studies showing men to have a higher (56), similar (57,58), or
lower (59,60) prevalence of abnormal ABIs. From data of the National Health and Nutrition
Examination Survey, PAD prevalence based on an ABI of <0.9 was shown to be similar in men
and women, but borderline values (>0.9 and <1.0) were much higher in women (61). An ABI-
based study of PAD estimated that the annual incidence in men was 1.7 per 1,000 for ages 40-
54, 1.5 per 1,000 for ages 55-64, and 18 per 1,000 for ages 65. Women had a higher annual
incidence: 6, 9, and 23 per 1,000, respectively, for the same age groups (62). Claudication
incidence and prevalence are higher in men than in women in some (56,59) but not all (57,63)
studies.
PAD defined either by intermittent claudication (64) or by ABI (65, 66, 67) is a potent predictor
of cardiovascular mortality (with a two- to sixfold hazard ratio) after adjusting for conventional
risk factors (68). The coprevalence of PAD with other atherosclerotic disease is significant.
Coronary artery disease has been reported in 60% to 80% of patients with PAD (69, 70, 71),
and a history of myocardial infarction and stroke in patients with PAD is 2.5- to 3.1-fold more
prevalent than in those without PAD. Conversely, a history of PAD is 2.1-fold more prevalent
in patients with a myocardial infarction (60, 68, 72). Approximately 25% to 30% of patients
with known coronary artery disease or cerebrovascular disease also have lower extremity
PAD (68).
Clinical Presentation and Evaluation

The evaluation of at-risk patients (Table 1-1) begins with the history and includes queries to
determine the presence of claudication, rest pain, or symptoms of systemic atherosclerosis
such as angina and cerebrovascular ischemia. The history should also assess the presence of
risk factor for atherosclerosis including age, smoking status, diabetes, known dyslipidemia, and
family history of premature atherosclerosis. Intermittent claudication is the classic symptom of
lower extremity PAD. Intermittent claudication is typically described as
an ache, tightness, burning, heaviness, or sense of fatigue in an exercising limb, usually
provoked by walking. The symptoms should localize to a muscular bed such as the calf and
resolve quickly with rest. The buttocks, thigh, or foot may be affected, depending on the
location of the stenotic lesions. The Rutherford-Baker scale (Table 1-2) can be used to
categorize patients with intermittent claudication and aid in communication between physicians.
However, history questionnaires can underestimate the prevalence of lower extremity PAD by
50% (73); a patient's symptoms can be atypical (reduced leg discomfort despite continued
effort, gait disturbance, decreased walking speed) or nonexistent. Despite of the absence of
classic symptoms, patients with lower extremity PAD have a marked reduction in quality of life
(74) as well as an increased risk for systemic atherosclerosis. Critical limb ischemia (CLI)
occurs when blood supply is inadequate to meet the metabolic demands of the tissues at rest.
Symptoms of CLI include persistent pain or paresthesias in the foot or toes at rest, nonhealing
ulcers, and tissue gangrene. Other symptoms of CLI include hypesthesia, cold intolerance,
muscular weakness, and joint stiffness. The patient may find relief from pain by placing the limb
in a dependent position. Acute limb ischemia (ALI) most often occurs as a consequence of total
vascular occlusion from atherothrombosis, graft occlusion, or embolism. ALI is defined as
ischemia of 2 weeks' duration and often presents as sudden development of symptoms or
development over several hours or days. The sudden decrease in perfusion threatens viability
of a limb and is a clinical emergency. Symptoms include worsening claudication and rest pain in
the limb. In severe cases, numbness and loss of motor function develop. The mnemonic of the
5 Ps is often used to remind clinicians of the symptoms of ALI: paresthesia, pain, pallor,
pulselessness, and paralysis. A loss of temperature regulation can also lead to a sixth P:
poikilothermia.
TABLE 1-1 INDIVIDUALS AT RISK FOR LOWER EXTREMITY PERIPHERAL

ARTERIAL DISEASE
Age <50 years, with diabetes and one other atherosclerosis risk factor (smoking,
dyslipidemia, hypertension, or hyperhomocystinemia)
Age 50-69 years and history of smoking or diabetes
Age 70 years
Legs symptoms with exertion (suggestive of claudication) or ischemic rest pain
Abnormal lower extremity pulse examination
Known atherosclerotic coronary, carotid, or renal artery disease
Source: Reprinted with permission from ACC/AHA 2005 Practice Guidelines for
Management of Patients with Peripheral Arterial Disease (Lower Extremities, Renal
Mesenteric, Abdominal Aortic) 2005, American Heart Association.
TABLE 1-2 RUTHERFORD-BAKER SCALE OF SEVERITY OF PERIPHERAL
ARTERIAL DISEASE
Grade Category Clinical description Objective criteria
0 0 Asymptomatic Normal treadmill test
Ankle pressure after exercise <50

mm Hg but >25 mm Hg less than
brachial
I 1 Mild claudication More moderate symptoms
Does not complete treadmill test;

2 Moderate claudication ankle pressure after exercise <50
mm Hg
Resting ankle pressure <60 mm Hg;

3 Severe claudication
decreased pulse volume recording
II 4 Ischemic rest pain
Resting ankle pressure <40 mm Hg;

Minor tissue loss; nonhealing
5 pulse volume recording moderately
ulcers
decreased
Major tissue loss above the

III 6 metatarsal limb no longer As noted for category 5
salvageable
Source: Reprinted with permission from ACC/AHA 2005 Practice Guidelines for
Management of Patients with Peripheral Arterial Disease (Lower Extremities, Renal
Mesenteric, Abdominal Aortic) 2005, American Heart Association.
A vascular examination includes palpation of carotid, brachial, radial, femoral, popliteal, dorsalis
pedis, and posterior tibial pulses and auscultation for carotid, supra- and infraclavicular,
abdominal, and femoral bruits. Assessment of skin (temperature and color tone, trophic skin
changes, distal hair loss, hypertrophic nails, elevation pallor, and dependent rubor) provides
important clues for diagnosis. A new finding of absent pulses is consistent with ALI; the location
of the pulse deficit helps to predict the site of arterial occlusion. When ALI is suspected, careful
assessment of limb temperature and edema, sensation, and motor strength must be
performed. The severity and prognosis of acute limb ischemia can be described using the
Society for Vascular Surgery/International Society for Cardiac Vascular Surgery classification
scheme (Table 1-3).
Noninvasive Vascular Testing

Assessment by ABI measurement should be performed in all patients at risk for PAD (75). The
ABI is a ratio of the systolic blood pressure at the ankle and brachial artery. Measurement is a
simple procedure and is done by inflating a sphygmomanometric cuff to suprasystolic pressure,
slowly deflating it, and detecting the onset of systolic pressure using a Doppler
ultrasound probe placed over the artery. Measurements are taken on both arms and the
dorsalis pedis and posterior tibial artery in each leg. The highest arm pressure is used for the
denominator of the index because atherosclerotic disease may occur in the subclavian or
axillary arteries and reduce pressure in the affected arm. Normal indexes are illustrated in Fig.
1-3. The ABI does not reliably correlate with symptoms. However, an ABI of <0.6 is related to
development of a walking impairment, and patients with an ABI of <0.4 are more likely to
experience ischemic rest pain. ABIs <0.9 have a sensitivity of 79% to 95% and a specificity of
96% to 100% for detecting lower extremity PAD compared with the gold standard of
angiography (76,77).
TABLE 1-3 CLINICAL CATEGORIES OF ACUTE LIMB ISCHEMIA
Arterial Venous
Muscle
Category Description/prognosis Sensory loss Doppler Doppler
weakness
signals signals
Not immediately
Viable None None Audible Audible
threatened
Minimal
Threatened Salvageable if (Often)
(toes) or None Audible
marginally promptly treated inaudible
one
More than
Salvageable toes;
Threatened Mild, (Usually
with immediate associated Audible
immediately moderate inaudible)
revascularization with rest
pain
Major tissue
Profound
loss or Profound,
Irreversible paralysis Inaudible Inaudible
permanent anesthetic
(rigor)
nerve damage
Source: Reprinted from Rutherford RB, et al. Recommended standards for reports
dealing with lower extremity ischemia: revised version. J Vasc Surg. 6:517-538,
1997, with permission from The Society for Vascular Surgery.
Noninvasive laboratory testing provides physiological information such as limb perfusion

pressure or anatomical information such as lesion location and severity. This information
complements that derived from the physical examination, and is useful when intervention is
contemplated. Limb segmental systolic pressure measurements are assessed similarly to the
ABI, but additional sphygmomanometric cuffs are placed on the proximal thigh, distal thigh, and
calf. Arterial pressure gradients of >20mm Hg between consecutive cuffs indicate the presence
of a hemodynamically significant stenosis (Fig. 1-4). In the setting of vascular calcification and
noncompressible vessels, a toe brachial index (TBI) can be obtaineda TBI of 0.7 is
consistent with PAD. Pulse volume recordings are measured by pneumatic plethysmography
(volume measurement) and depict the change in volume of a limb segment with each pulse. The
pulse volume recordings can be determined at the same sites as segmental pressures. A
normal waveform has a rapid upstroke, dicrotic notch, and downstroke. As stenosis impairs
distal blood flow, the dicrotic notch is lost, upstroke is delayed, and the amplitude is diminished
(Fig. 1-4). The combined use of limb segmental pressure measurments and pulse volume
recordings results in a 95% accuracy in identification of significant stenoses (78). If the
segmental Doppler pressure/pulse volume recordings results are within normal range, and the
suspicion of PAD remains high, treadmill testing can be performed; exercise increases the
sensitivity of the ABI. Either fixed or dynamic treadmill exercise protocols can be used.
Typically, the patient walks on a treadmill until symptomatic, then ABIs are measured within 1
minute of exercise cessation and compared to rest ABIs. The ABI should decrease by at least
20% with exercise in a patient with hemodynamically significant PAD.
Imaging (ultrasound, contrast-enhanced computer tomography [CT], or magnetic resonance
angiography [MRA]) of limb vasculature is performed when noninvasive testing indicates
disease and revascularization is being considered. For lower extremity PAD, this is often when
patients have Rutherford scale 2 symptoms and signs. Imaging is discussed in detail in
Chapters 5, 6, 7 and 8.
Differential Diagnosis
If complaints suggestive of intermittent claudication are elicited, a complete evaluation must
include consideration of nonatherosclerotic causes of PAD and nonvascular causes of exertional
leg pain. The differential diagnosis is listed in Table 1-4. Popliteal artery entrapment occurs
when a congenitally anomalous origin of the medial head of the gastrocnemius muscle causes
displacement or compression of the popliteal artery. This should be considered especially when
the patient is young and athletic. It affects males more often than females (79) and is treated
surgically. Exertional compartment syndrome is believed to be caused by inhibition of venous
outflow by large calf muscles. Increased tissue pressure limits microvascular flow and results in
calf pain or tightness. This syndrome is also most often seen in athletes. Symptoms improve
with leg elevation after cessation of exercise. Endofibrosis of the external iliac artery is a rare
occurrence in highly trained bicyclists or other endurance atheletes but can cause claudication.
While FMD most commonly affects the renal and carotid arteries, it may involve any of the
arteries in the lower extremities, the iliac arteries being the most common. Venous claudication
may occur when proximal venous beds are thrombosed or compressed, limiting outflow. An
increase in arterial flow with exercise increases venous pressure markedly and causes severe
tightness and, frequently, leg edema. The symptoms often improve with leg elevation after
cessation of exercise. Adventitial cysts are most often found in young patients at the region of
the proximal popliteal artery. Symptoms include claudication, the onset of which may be sudden
if the cyst ruptures and causes sudden stenosis of the artery via extrusion of contents into the
vascular lumen. Decreased popliteal and distal pulses may be exacerbated by full flexion of the
knee, which causes occlusion of the stenosed vessel. Vasculitides are infrequent causes of
claudication and are discussed in Chapter 2.
Nonvascular causes of walking-related leg pain include lumbar radiculopathy, spinal stenosis,
osteoarthritis, and myositis. Pain or paresthesias that affect the posterior aspect of the leg,
which occurs with specific positions such as standing or develops immediately upon walking,
may be due to lumbar radiculopathy or spinal stenosis. Symptoms may improve with
leaning forward because the compression on nerve roots is reduced. Osteoarthritis causes pain
with exercise. However, the pain is not brought on by a predictable level of exertion and does
not resolve rapidly upon discontinuation of activity.
FIGURE 1-3. Meaurement of the ankle-brachial index (ABI). Systolic blood pressure is
measured in each arm and in the dorsalis pedis (DP) and posterior tibial (PT) arteries in
each ankle. The higher of the two arm pressures is selected, as is the higher of the two
pressures in each ankle. The right and left ABI values are determined by dividing the higher
ankle pressure in each leg by the higher arm pressure. The ranges of the ABI values are
shown, with a ratio >1.30 suggesting a noncompressible, calcified vessel. In this condition,
the true pressure at that location cannot be obtained, and additional tests are required to
diagnose peripheral arterial disease. Patients with claudication typically have ABI values
ranging from 0.41 to 0.90, and those with critical leg ischemia have values of 0.40.
(Reproduced with permission from Hiatt WR. Medical treatment of peripheral arterial
disease and claudication. N Engl J Med. 2001;344:1608-1621. 2001, Massachusetts
Medical Society. All rights reserved.) (See the color insert.)
Management
The goal of medical therapy for lower extremity PAD is to reduce the risk of systemic
cardiovascular events, such as myocardial infarction or stroke, and to improve limb-related
symptoms and outcomes (claudication, CLI, amputation). Strategies to reduce the risk of
adverse cardiovascular events include aggressive risk factor modification and antiplatelet
therapy.
The risk of PAD in smokers is three- to fourfold that of nonsmokers (59). Smoking cessation
improves outcomes including walking times (80), CLI (81), patency of grafts (82), and
amputation (83). Unfortunately, the efficacy of counseling is low (84). Organized cessation
programs, nicotine replacement therapy, and buproprion increase abstinence rates and reduce
recidivism (85). Varenicline, a partial nicotinic acetylcholine receptor agonist, has recently been
demonstrated to be more efficacious than buproprion in assisting smoking cessation (86). PAD
patients should be treated with lipid lowering agents, especially HMG CoA reductase inhibitor
(statins). Both
total cholesterol and LDL cholesterol are risk factors for lower extremity PAD (72,87). The
association of triglycerides of high-density lipoprotein and PAD risk is controversial (88,89).
Most studies that evaluated statin therapy were designed for coronary artery disease, not
lower extremity PAD. However, the results from the coronary disease studies are relevant
because of the prevalence or coronary artery disease in patients with lower extremity disease.
In the Heart Protection Study, simvastatin reduced the incidence of a first major vascular event
in patients with lower extremity PAD (90,91). Thus, statins are recommended for all patients
with lower extremity PAD, with a target LDL cholesterol of <100 mg/ml. Statins also have been
shown to improve intermittent claudication (92, 93, 94, 95).
FIGURE 1-4. Segmental pressure measurements. Sequential Doppler pressures are

measured by placing sphygmomanometric cuffs on the proximal thigh, distal thigh, calf, and
ankle. The cuffs are inflated above systolic pressure and then slowly depressurized.
Simultaneously, a Doppler probe, placed over the dorsalis pedis or posterior tibial artery,
monitors the pressure. As the cuff is slowly deflated, the reappearance of a Doppler signal
indicates the systolic pressure at the level of the cuff that permits blood flow. Arterial
stenosis or occlusion will decrease the perfusion pressure. Arterial pressure gradients
between cuffs indicate the presence of a stenosis. In this example, arterial pressures (mm
Hg) are noted in the location of each sphygmomanometric cuff. The patient shows
evidence of a systolic gradient between the left lower thigh and the left calf cuffs indicative
of distal superficial femoral artery and/or popliteal artery occlusive disease. (See the color
insert.)
TABLE 1-4 DIFFERENTIAL DIAGNOSIS OF EXERTIONAL LEG PAIN
Nonatherosclerotic vascular disease
Popliteal artery entrapment
Exertional compartment syndrome
Endofibrosis of the external iliac artery
Fibromuscular dysplasia
Venous claudication
Adventitial cysts
Vasculitis
Thromboangiitis obliterans
Takayasu arteritis
Giant cell arteritis
Nonvascular causes
Lumbar radiculopathy
Spinal stenosis
Hip/knee arthritis
Myositis
Intensive blood pressure control significantly reduces the relative risk of cardiovascular events
in these patients (96,97). Angiotensin-converting enzyme (ACE) inhibitors should be considered
first-line agentseven normotensive patients with PAD may benefit from ACE-inhibitor therapy
(97). Additionally, despite conventional teaching, -blockers do not worsen intermittent
claudication, and most patients do well on these agents (98). Only in the small subset of
patients with CLI does particular caution need to be exercised with antihypertensive therapy, as
reduction in perfusion pressure may exacerbate the ischemia. Nonetheless, these patients do
require long-term antihypertensive therapy.
Tight control of blood glucose levels in Type 1 and Type 2 diabetics has not been shown to
have a significant effect on large vessel end points, even when improvement in microvascular
events (i.e., retinopathy, nephropathy) is demonstrated (99,100). The insulin sensitizer and
PPAR agonist, pioglitazone, demonstrated a nonsignificant reduction in a composite primary
outcome of time to all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary
syndrome, revascularization of coronary or lower extremity arteries, or above-the-knee
amputation. Reduction in the main secondary outcome was significant, however, with patients in
the pioglitazone group demonstrating fewer deaths, myocardial infarctions, and strokes than
those in the placebo group. Fewer patients in the pioglitazone group required the addition of
insulin to their medication regimen compared to those in the placebo group (101). The American
Diabetes Association has published guidelines for patients with PAD (102,103). Prevention of
microvascular complications is improved by meeting a goal hemoglobin A1c of <7%.
Homocystinemia is an independent risk factor for PAD (104,105) as well as being associated
with a hypercoagulable state (106,107). Treatment with folic acid and vitamins B12 and B6
lowers homocysteine levels. However, homocysteine-lowering therapy does not improve
cardiac events or PAD outcomes (108,109).
Antiplatelet therapy is indicated in patients with lower extremity PAD to reduce the risk of
adverse cardiovascular
outcomes (75). Aspirin is a cyclo-oxygenase inhibitor and has been demonstrated to reduce the
need for lower extremity revascularization (110,111), major vascular events (112), and graft
occlusion (113). Aspirin decreases the risk of thrombosis at sites of atherosclerotic lesions.
Aspirin reduces the risk of adverse cardiovascular outcomes, such as myocardial infarction,
stroke, and vascular death, in patients with coronary disease, but no trial has specifically
examined the effect of aspirin on cardiovascular outcomes among patients with PAD. However,
a meta-analysis of smaller antiplatelet trials, some of which included aspirin, demonstrate that
antiplatelet drugs reduce the occurrence of these events (112). The thienopyridine derivative,
clopidogrel, interferes with platelet function by blocking the antiplatelet drug receptor. One trial
found that clopidogrel had greater efficacy than aspirin in preventing cardiovascular events in
patients with lower extremity PAD (70). Dual antiplatelet therapy with clopidogrel and aspirin,
compared to aspirin alone, did not improve outcomes in a large trial of patients with
documented coronary artery disease, PAD, and cerbrovascular disease and those with multiple
risk factors or asymptomatic atherosclerosis (114,115). Subgroup analysis for patients with
lower extremity PAD has not yet been published for the most recent trial (115). Thus, current
recommendations are that all patients with lower extremity PAD should receive antiplatelet
therapy with either aspirin at 75 to 325 mg/day or clopidogrel at 75 mg/day (75).
Few studies have addressed the role of anticoagulation in lower extremity PAD. In coronary
artery disease patients, moderate- to high-intensity therapy (INR 2-3) did show a reduction in
end points over aspirin but was associated with a twofold increase in major bleeding (116,117).
Small studies have shown no benefit of warfarin over aspirin for intermittent claudication (118).
Similarly, there is no overall difference in graft occlusion between oral anticoagulation and
aspirin therapy, although subset analysis did show a modest reduction in graft occlusion in
patients with venous bypass grafts. Overall, oral anticoagulation was again associated with an
approximately twofold increase in major bleeding (119).
Thus, oral anticoagulation with warfarin is not routinely recommended for treatment of PAD. It
may be used, however, following an episode of acute limb ischemia or in patients with chronic
lower extremity PAD when they have another indication for oral anticoagulation, such as atrial
fibrillation or a mechanical heart valve.
Medical therapy to improve symptoms of claudication are limited and include exercise
rehabilitation and two U. S. Food and Drug Administration (FDA)-approved drugs. Supervised
programs improve walking duration, speed, and distance in patients with intermittent
claudication by 80% to 180% (120,121). In contrast, unsupervised home-based training
produces negligible benefit. The benefits of exercise are due to a combination of increased
oxidative capacity of skeletal muscles and better walking mechanics and, possibly, collateral
blood vessel development, enhancement of nitric oxide-mediated vasodilation, and improved
hemorrheology (122). All patients with lower extremity PAD should be enrolled in supervised
exercise programs and undergo comprehensive cardiovascular risk assessment with a treadmill
exercise test prior to initiation of the program. The programs should utilize a treadmill or track in
sessions of 45 to 60 minutes at least three times a week for a minimum of 12 weeks (75).
During the exercise session, patients should walk until moderate to severe symptoms of
claudication develop, rest until they resolve, and then continue with the exercise. This cycle
should be repeated for the duration of the 45- to 60-minute training period.
There are two drugs approved by the FDA for treatment of intermittent claudication. Cilostozol
is a phosphodiesterase III inhibitor that has vasodilator and antiplatelet properties, yet its
precise mechanism of action in unknown. At doses of 50 to 100 mg twice daily, cilostozol
significantly improves pain-free and maximal walking distance (123). Side effects include
headache, diarrhea, and palpitations. By inference from studies showing increased mortality in
patients with congestive heart failure treated with other phosphodiesterase III inhibitors,
milrinone and vesnarinone, cilastozol should not be administered to patients with congestive
heart failure (124,125). Pentoxifylline is a methylxanthine derivative with the purported effect of
decreasing blood viscosity. It was approved for the treatment of intermittent claudication more
than 20 years ago, but multiple trials have shown disparate effects, and clinical efficacy is still
not well established (126). Parenteral administration of vasodilator prostaglandins may help a
small subset of patients by reducing pain in CLI or improved healing of ulcers (75), but they do
not reduce the risk of amputation or death in these patients, nor do they improve walking times
in patients with intermittent claudication (127).
Several agents are undergoing investigation. These include the angiogenic growth factors,
vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and the transcription
factor, hypoxia inducible factor-1 (HIF1). Intrafemoral artery administration of recombinant
FGF-2 improved peaking walking time in one study (128); intramuscular administration of an
adenovirus encoding VEGF121 did not improve walking time in a placebo-controlled trial (129).
Further clinical studies are ongoing. Propionyl-L-carnitine affects metabolic function and has had
a favorable effect on walking distance in several initial trials (130). Some have advocated the
use of nutriceuticals or vitamin supplementation to treat claudication, but benefit either is
marginal or does not occur. In large, randomized trials vitamin E did not show efficacy in
reducing cardiac or vascular events (91,97). Supplementation with L-arginine as a substrate for
synthesis of nitric oxide has not proven efficacious post-myocardial infarction and there is not
sufficient evidence to address its role in patients with PAD (131). Studies are too limited to
provide recommendations for efficacy in PAD. Ginkgo biloba is one of the top-selling herbal
medicinal products in the United States. Meta-analysis of eight studies indicates that this agent
may improve walking time (132), but the clinical significance of this improvement is
questionable.
Generally, endovascular or surgical revascularization is considered for chronic lower extremity
PAD when disabling claudication persists despite medical management/risk modification,
exercise, and drug therapy or CLI develops (Fig. 1-5). Endovascular intervention is covered
elsewhere in this text. Patients with acute limb ischemia require urgent medical and
interventional attention. Initial medical therapy for patients with threatened limb loss includes
systemic anticoagulation with intravenous unfractionated heparin. Prompt angiographic imaging
should follow. Revascularization strategies for ALI are discussed elsewhere in this text. Long-
term therapy includes treatment of the underlying cause and antithrombotic therapy (antiplatelet
therapy for atherothrombosis, warfarin for most other causes).
ABDOMINAL AORTIC ANEURYSMS

Etiology
Aortic aneurysms are defined as an increase in diameter of the aorta by 50% compared with
the adjacent normal segment of the aorta. More modest expansion is designated ectasia. In
adults, the diameter of the aorta is 3 cm at the root, 2.5 cm
in the descending thoracic segment, and 2 cm in the abdomen. Aortic aneurysms are classified
as fusiform when the expansion is circumferential and saccular when there is an outpouching of
a segment. In contrast to true aneurysms, pseudoaneurysms are not aneurysms but contained
ruptures of the aorta.
FIGURE 1-5. Treatment of claudication. *Inflow disease should be suspected in individuals
with gluteal or thigh claudication and femoral pulse diminution or bruit and should be
confirmed by noninvasive vascular laboratory diagnostic evidence of aortoiliac stenoses.
Outflow disease represents femoropopliteal and infrapopliteal stenoses (the presence of
occlusive lesions in the lower extremity arterial tree below the inguinal ligament from the
common femoral artery to the pedal vessels). PAD, peripheral arterial disease. (Reprinted
with permission from ACC/AHA 2005 Practice Guidelines for Management of Patients
with Peripheral Arterial Disease [Lower Extremities, Renal Mesenteric, Abdominal Aortic]
2005, American Heart Association.)
As in atherosclerosis, the development of aortic aneurysms involves inflammatory mediators

and proteolytic degradation by matrix metalloproteinases. However, the process resulting in
aneurysm formation is fundamentally different from the intimal proliferative process that
determines atherosclerotic arterial occlusive disease. Progressive weakening of the adventitia
and media leads to aneurysmal disease by decreasing the aortic tensile strength, leading
ultimately to thinning, dilatation, and rupture (133). Tensile strength of the aorta is conferred by
elastin in the tunica media. It is the elasticity of the aorta that permits it to withstand the
biomechanical wall stress of pulsatile blood flow. In aortic aneurysms, elastin is fragmented,
and glycosaminoglycans, collagen, and fibronectin are deposited, each leading to increased
aortic rigidity and a weakening of the vessel wall (134,135). The abdominal aorta is
predisposed to a higher rate of aneurysm than more proximal segments for at least three
reasons: (1) elastin content gradually decreases with distance from the heart (136), (2) the
abdominal aorta has a decreased density of the nutritive vasa vasorum and, thus, decreased
aortic wall perfusion (137), and (3) the infrarenal aorta is exposed to higher levels of oscillating
flow and reflected pressure waves, resulting in higher levels of aortic wall tension (138).
Although most aortic aneurysms occur as a result of the degenerative processes described
above, certain disease states including vasculitis (discussed in Chapter 2), infection, and
inherited abnormalities predispose to aortic aneurysm formation. Further discussion of these
conditions is beyond the scope of this chapter.
Epidemiology
Infrarenal abdominal aortic aneurysms (AAAs) represent ~90% of all aortic aneurysms.
Thoracoabdominal aneurysms (contiguous involvement of the descending thoracic aorta and
abdominal aorta) represent <5% of all aortic aneurysms (139, 140), however, they have a high
proportion of rupture (141).
The prevalence of AAA ranges from 0.7% to 8.4% (133). Prevalence is higher in men than
women. Prevalence in males of AAA, defined as an infrarenal aortic diameter of >3 cm, is 3.6%
(142), while only 1% of females have AAAs (143). The prevalence of AAA increases with age.
The prevalence of AAA is <1% in men aged 25 to 44 years, increases to 6% by ages 55 to 65,
and is 19% for people aged 75 to 84 years (144). Family history is also a strong predictor
there is a nearly 10-fold increase in relative risk with an affected male sibling and a 23-fold
increase when a female sibling is affected (145). No single candidate gene has yet been
identified that explains the family association.
Cigarette smoking is the most potent modifiable risk factor for AAA and accounts for the vast
majority of AAA in the population (146). Risk increases threefold with any smoking history
(147), and there is a dose-response relationship (148). Lesser risk factors include hypertension
(particularly diastolic hypertension) (149,150), elevated cholesterol (151,152), and
the presence of other atherosclerotic disease (153,154). In contrast, the presence of diabetes
decreases the risk of aneurysm formation by 30% to 50% (142,150).

Most AAAs are asymptomatic and are usually found when a pulsatile abdominal mass is
detected upon physical examination or incidentally upon imaging for an unrelated reason.
Proper physical examination may detect the AAA in ~50% of the patients in whom it is present
(155). Occasionally an AAA will cause epigastric, lower back, or abdominal pain. When large,
an AAA may cause compression of adjacent structures. For example, compression of the left
iliac vein may cause left leg swelling. Rarer symptoms include erosion of contiguous structures
such as the vertebral bodies or nerve root compression causing radiculopathy (156). Aortic
rupture usually presents with the patient in extreme distress or with death from circulatory
collapse. The factor most predictive of rupture is the initial size of the aneurysm (157). In the U.
K. Small Aneurysm Study, the rate of rupture was 0.9% for aneurysms 3 to 3.9 cm, 2.7% for
aneurysms 4 to 5.5 cm, and 28% for aneurysms 5.6 cm (158). Women had a threefold higher
risk of rupture than men. In a prospective study of patients with larger aneurysms who were
unwilling or unable to undergo elective repair, the 1-year incidence of rupture was 9% for
aneurysms of 5.5 to 5.9 cm, 10% for aneurysms of 6.0 to 6.9 cm (19% for the 6.5- to 6.9-cm
subgroup), and 32% for AAA of 7.0 cm (159).
Screening guidelines have been written with the aim of detecting aneurysms prior to rupture
(75,160). A large, prospective trial found a long-term, cost-effective aneurysm-related mortality
benefit of screening (161). Building on these guidelines, the SAAVE (Screening Abdominal
Aortic Aneurysms Very Efficiently) Act was signed into law, and beginning in 2007, Medicare
will pay for a one-time ultrasound screening for all men and women with a family history of AAA
and for men over ages 65 to 75 who have ever smoked. Ultrasonography is rapid, is easily
performed, and has a sensitivity approaching 100% for detecting AAA aneurysms of 3 cm
(162). When an aneurysm is found, serial surveillance examinations should be performed at
frequencies determined by the size of the aneurysm to monitor the rate of expansion (163).A
recent recommendation, based on analysis of aneurysm growth rates in small aneurysm
studies, is the following: for AAAs with baseline diameters of <3.5, 4.0, 4., and 5.0 cm, the
screening intervals are 36, 24, 12, and 3 months, respectively (163).
Management
Medical management is limited. -Blockers do not appear to be efficacious in reducing
aneurysm growth (164). In experimental models (165) and a small phase 2 trial (166)
antibiotics (e.g., doxycycline) with inhibitory effects on the matrix metalloproteinases have
slowed aneurysm growth. Statins may reduce the rate of aneurysm expansion (167,168).
Randomized prospective studies comparing immediate surgical treatment with serial ultrasound
or CT surveillance of symptomless AAAs <5.4 cm in diameter have demonstrated that there is
no survival benefit of early surgical repair (169,170). These studies have been used to support
the convention for repair of AAAs when the maximal diameter approaches 5.5 cm.
Endovascular repair of AAAs is discussed in Chapter 12.
Iliac, Femoral, and Popliteal Artery Aneurysms

Isolated aneurysms of the iliac arteries are infrequent (171). However, 10% to 20% of patients
with AAA have involvement of the iliac arteries (172). The prevalence of iliac artery aneurysms
has been estimated as 3.6 in 100,000 (173). Rupture of iliac artery aneurysms <3 cm rarely
occurs (174), however, the mortality of rupture is high (175). Repair is generally recommended
for aneurysms >3 cm (172,174,176). Surveillance by serial imaging is done with contrast-
enhanced CT or MRA, compared to AAA surveillance, for which ultrasound is recommended.
Isolated atherosclerotic aneurysms of the superficial femoral artery are also rare. In ~70% of
cases other aneurysms are present, most often AAAs (177). To decrease the risk of rupture or
thrombosis and limb ischemia, repair is recommended when the aneurysm becomes greater
than twice the normal vessel size (178).
Popliteal arteries are considered aneurysmal if the diameter is >0.7 cm (179). The etiology of
these aneurysms is incompletely defined but is often associated with antherosclerotic
aneurysmal disease of other vessels. Popliteal artery aneurysms are the most common
peripheral artery aneurysm, estimated to be between 4% and 12% as prevalent as AAAs
(180,181). They are bilateral in >50% of cases and coexist with an AAA in 30% to 50% of
cases. There is a strong male predilection for popliteal artery aneurysms (182). Ultrasound is
an excellent imaging modality for these aneurysms and can determine patency, the presence of
thrombus, and differentiate the aneurysms from popliteal masses such as Baker's cysts (179).
Complications such as thrombosis, distal embolization, or rupture occur in 18% to 31% of
causes that are not surgically corrected (183), thus repair is recommended for any patient not
considered to be at high surgical risk (181).
RENAL ARTERY DISEASE

Etiology
Renal artery disease may be caused by atherosclerosis, FMD, thromboembolism, or vasculitis.
Approximately 75% to 90% of renal artery stenoses (RAS) are due to atherosclerosis (184).
FMD is the second most common cause of RAS (40). It accounts for ~25% of cases of
renovascular hypertension and ~2% of all cases of hypertension (40). While atherosclerotic
lesions typically affect the ostium or proximal segment of the renal arteries, FMD (medial
dysplasia subtype) affects the middle and distal two thirds of the arteries and has a string-of-
beads appearance on imaging.
Epidemiology/Prognosis
RAS is a common disease, with an overall prevalence of 6.8% in individuals 65 years of age
(185). Bilateral RAS is common, seen in 40% to 50% of cases (186). Atherosclerotic RAS is
associated with atherosclerosis of other vascular beds. In patients undergoing screening during
cardiac catheterization, 11% to 18% have RAS >50% (187, 188, 189). RAS is found in ~25%
to 60% of patients with atherosclerotic disease of the carotid artery or lower extremity arteries
(75). Risk factors for the presence of RAS include age, smoking, dyslipidemia, hypertension,
and diabetes. Atherosclerotic RAS is often a progressive disorder, with the percentage
stenosis increasing at rates of between 7% and 14% per year (190, 191, 192). Over a 5-year
follow-up period, occlusion occurs in ~40% of cases where the stenosis was originally noted to
be >75% (193). Occlusion occurs most often in patients with high-grade stenosis, severe
hypertension, and diabetes (191).
Severe atherosclerotic RAS is independently associated with mortality, even in patients who
have undergone coronary revascularization. In one study 4-year survival rates in patients
undergoing renal artery screening during cardiac catheterization were 90% without RAS, ~70%
with a 50% to 95% stenosis, and 48% with a stenosis >95% (194). Whether RAS directly
accelerates cardiovascular mortality or is simply a marker of atherosclerotic burden is not
known.
The major pathophysiological consequences of RAS are renovascular hypertension and renal
insufficiency. The reninangiotensin system is activated when increased levels of renin are
released from the underperfused kidney supplied by a stenotic artery. Thereafter, maintenance
of renovascular hypertension depends, in part, on volume expansion, leading to a complex
feedback loop involving pressure natriuresis, a subsequent decrease in perfusion to the stenotic
kidney, and recurrent activation of the renin-angiotensin system (195). Renal insufficiency
secondary to RAS develops when the decrease in renal perfusion pressure outstrips the
kidney's autoregulatory responses. Diminished renal blood flow causes a decline in glomerular
filtration rate and, ultimately, renal tissue damage. The contribution of RAS to the development
of end-stage renal disease is not well defined, though renal artery occlusion generally causes
irreversible loss of renal excretory function. In a study of 683 patients entering dialysis, 12%
had RAS documented as the cause of renal failure (196). Despite its prevalence, RAS is a
relatively uncommon cause of hypertension (197,198). The presence of RAS in a hypertensive
patient does not necessarily mean it is the cause. A retrospective review of ~150 aortograms
demonstrated that approximately one half of patients with a stenosis of >50% did not have
hypertension (197). However, the presence of resistant hypertension (defined as the failure to
normalize blood pressure to <140/90 mm Hg with a medical regimen consisting of at least three
drugs with differing mechanisms of action, including a diuretic) should increase suspicion for
RAS as a cause (199). Malignant or accelerated hypertension is associated with a high
prevalence of RAS (200).

RAS should be suspected or ruled out when (1) the onset of hypertension is before the age of
30 years, (2) severe hypertension develops after age 55, (3) hypertension accelerates or is
resistant to full doses of a three-drug regimen that includes a diuretic, (4) a patient develops
worsened renal function after administration of an ACE-I or angiotensin receptor blocker, (5)
there is an atrophic kidney or a size discrepancy between kidneys of >1.5 cm, or (6) a patient
develops unexplained pulmonary edema or refractory angina (75).
The physical examination is generally not helpful in the diagnosis of RAS. Evidence of coronary,
cerebral, or lower extremity atherosclerosis increases the likelihood of RAS because of the
systemic nature of atherosclerosis (201). The presence of an abdominal bruit is common and
nonspecific; however, a bruit with both systolic and diastolic components, especially when
located over the epigastrium, may indicate RAS (202).
Imaging studies are the first-line tests for the diagnosis of RAS (75). In the past, indirect
methods such as intravenous urography, plasma renin activity, the captopril test, and renal vein
renin measurement were used to screen for RAS. These methods suffer variously from poor
sensitivity, specificity, or accuracy and have largely been replaced by any of several
sophisticated imaging modalities (203). Specifics of these modalities are described elsewhere
in this text. Diagnosis can be made with duplex ultrasound, contrast-enhanced CT angiography,
or MRA. The goal of imaging is to identify the main and accessory renal arteries, localize the
site of stenosis, determine the type of disease present (i.e., atherosclerosis or FMD), provide
evidence of hemodynamic significance of the stenosis, and predict the likelihood of a favorable
response to revascularization (204). No single imaging modality optimally fulfills all these
criteria. Thus, the choice of modality is determined by cost, availability, and local expertise.
Digital subtraction angiography is the most accurate test to diagnose RAS and should be
considered when the index of suspicion is high and noninvasive tests are inconclusive.
Management
The treatment of RAS includes medical therapy, percutaneous revascularization (angioplasty or
stenting), and surgical revascularization. For atherosclerotic RAS, risk factor modification, as
done for lower extremity PAD, is recommended (184). Medical management is largely focused
on blood pressure control with the same agents that are used for treatment of essential
hypertension, including calcium channel blockers and -blockers (205, 206). The use of ACE
inhibitors and angiotensin receptor blockers is somewhat controversial. These agents are
associated with a decline in renal function in 5% to 20% of patients with bilateral rRAS (207,
208, 209). In patients with unilateral stenosis, on the other hand, ACE-I and angiotensin
receptor blockers may be more effective than other antihypertensive agents in lowering blood
pressure (210), and in diabetic patients, in particular, these drugs interfere with the activated
rennin-angiotensin system and may decrease renal injury (211). Hypertension in patients with
FMD generally responds to ACE-I also. Blood pressure control does not appear to attenuate
progression of RAS (75). Risk factor modification by smoking cessation, treatment of
dyslipidemia, and use of aspirin are recommended for all patients with atherosclerotic RAS.
The clinical clues that help determine which patients with atherosclerotic RAS would best be
treated by medical therapy versus renal artery revascularization are an active area of
investigation. However, American College of Cardiology (ACA)/American Heart Association
(AHA) class II recommendations are in place for catheter-based revascularization for the
following scenarios: preservation of renal function, treatment of refractory hypertension,
congestive heart failure, and angina (Fig. 1-6). For patients with hypertension and FMD,
percutaneous angioplasty with stent bailout (212,213) or vascular surgical reconstruction in
patients with complex anatomy (214,215) should be considered (Fig. 1-6). Endovascular
treatment of RAS is discussed elsewhere. Currently, surgical revascularization is reserved by
most physicians for those patients whose disease meets these clinical criteria but whose
anatomy is not amenable to percutaneous treatment. Operative techniques used to correct
RAS include aortorenal bypass, thromboendarterectomy, renal artery reimplantation, and
splanchnorenal bypass (216).
Renal Artery Aneurysms

The incidence of renal artery aneurysms is unknown (217). Compared to RAS, renal artery
aneurysms are more likely to affect younger patients without atherosclerotic risk factors (218).
Hypertension is often coexistent and may be causal. Vasculitides resulting in aneurysmal
dilatation of the renal arteries include Behcet's disease and polyarteritis nodosa and are
discussed in Chapter 2. Rupture is the major complication of renal artery aneurysms; increased
rates of rupture are seen in
peripartum females. Repair is recommended for aneurysms >1.0 cm when hypertension is
present and, in the absence of hypertension, for aneurysms >1.5 to 2.0 cm (218).
FIGURE 1-6. Indications for renal revascularization. *Viable means kidney linear length >7
cm. It is recognized that renal artery surgery has proven efficacy in alleviating renal
arterial sclerosis (RAS) due to atherosclerosis and fibromuscular dysplasia. Currently,
however, its role is often reserved for individuals in whom less invasive percutaneous RAS
interventions are not feasible. CHF, congestive heart failure; CRI, chronic renal
insufficiency; LOE, level of evidence; PTA, percutaneous transluminal angioplasty.
(Reprinted with permission from ACC/AHA 2005 Practice Guidelines for Management of
Patients with Peripheral Arterial Disease [Lower Extremities, Renal Mesenteric,
Abdominal Aortic] 2005, American Heart Association.)
MESENTERIC ARTERY DISEASE

Etiology
Mesenteric arteries are subject to the same disease processes and complications as the aorta.
Mesenteric ischemia from stenosis or occlusion of the arteries is the most common clinical
consequence of mesenteric artery disease. In evaluation of mesenteric ischemia it is helpful
first to categorize the course of ischemia as chronic or acute, because the presentation,
diagnosis, and treatment of these two entities differ greatly. Chronic ischemia is almost
exclusively caused by stenotic atherosclerotic disease. Involvement of the celiac vessels by
atherosclerosis is common, but clinical ischemia is rare. This is most likely because of the
extensive interconnection among the celiac, superior mesenteric, and inferior mesenteric
arteries, giving each vascular bed more than one source of blood supply (219). However,
single-vessel disease (often the superior mesenteric artery) has been documented to result in
ischemia (220,221). Nonatherosclerotic causes of chronic mesenteric ischemia include external
compression by the median arcuate ligament (celiac axis compression syndrome). The median
arcuate ligament is the fibrous arch that connects the diaphragmatic crura on either side of the
aortic hiatus. With low insertion, it can cross the proximal portion of the celiac axis, causing
compression. Other conditions associated with chronic mesenteric ischemia include
neurofibromatosis, radiation injury, congenital afibrinogenemia, Cogan's syndrome and vasculitis
related to rheumatoid arthritis, systemic lupus erythematosis, and polyarteritis nodosa. The
etiology of acute mesenteric ischemia is largely due to atherothrombosis at sites of
atherosclerosis, in situ thrombosis secondary to arteritis, hypercoagulable state, aneurysm, or
dissection, and arterial thromboemboli from cardiac or proximal arterial sources (222, 223, 224,
225, 226). Nonocclusive acute ischemia is caused by low-flow states as in cardiogenic or septic
shock (223,227,228) or vasospasm from drugs (e. g., vasopressin, norepinephrine,
ergotamines, cocaine) (229,230).
Epidemiology
The prevalence of mesenteric artery stenosis in Americans >65 years of age is ~18% (231).
Although there is a high prevalence of mesenteric atherosclerosis, symptomatic chronic arterial
insufficiency is infrequently encountered (232,233). Seventy percent of patients with
atherosclerotic chronic mesenteric ischemia are females with a history of cardiovascular
disease. Approximately 30% to 50% of patients have had previous procedures for occlusive
atherosclerotic disease at other locations (234,235). The prevalence of celiac axis compression
syndrome is not known; most studies have not clearly distinguished between intrinsic and
extrinsic causes of stenosis (236). Acute
intestinal ischemia is relatively uncommon. The incidence of acute ischemia as the cause of
death has been estimated to be 2.0 per 100,000 person years (237). Risk factors for fatal
nonocclusive mesenteric included cardiac failure, atrial fibrillation, and recent surgery. Similarly
to patients with chronic mesenteric ischemia, two thirds of patients with acute ischemia are
women. The median age is 70 years, and most have a history of cardiovascular disease (222,
223, 224,238).

The major symptom of chronic mesenteric ischemia is postprandial midabdominal or epigastric
pain and weight loss secondary to voluntary reduction in food intake. The diagnosis is often
delayed because of the numerous possible causes of abdominal pain that are often considered
initially. Mesenteric artery disease can be detected by ultrasound, contrast-enhanced CT
angiography, or MRA examination of the mesenteric arteries. Occasionally an enlarged arc of
Riolan (a collateral vessel connecting the inferior mesenteric artery distribution with the
superior mesenteric artery) is seen, and is an arteriographic sign of proximal mesenteric arterial
obstruction (75). However, diagnosis of mesenteric ischemia can be difficult even with high-
quality imaging; stenoses are common, and clinical ischemia rare. Diagnosis must take into
account the entire clinical presentation and be made in the absence of other obvious causes of
abdominal pain/weight loss.
Compression of the celiac axis can be visualized by imaging during inspiration and expiration
(compression worsens and peak systolic velocities increase with peak expiration) (239). There
has been some controversy over whether this compression truly causes ischemia, as a large
percentage of patients have a history of prior abdominal surgery, alcohol abuse, and psychiatric
disorders. The symptoms of celiac axis compression syndrome are varied but include pain and
weight loss from early satiety and gastric retention rather than food avoidance (236).
Patients suffering from acute intestinal ischemia present with severe abdominal pain out of
proportion to physical findings: peritoneal signs take hours to develop. Suspicion should be
increased in patients with cardiovascular disease, arrhythmias, or a recent myocardial infarction
and in those critically ill with decreased cardiac output and episodes of hypotension, after
arterial catheterization, or with previous signs of chronic mesenteric ischemia. Ultrasound
cannot be used for diagnosis, as this modality requires ideal conditions (fasting, etc.) to be
efficacious. Contrast-enhanced CT or arteriography, if time allows, is best (75).
Management
There are no randomized or controlled clinical trials of surgical or percutaneous intervention for
chronic mesenteric ischemia, and thus, there is no consensus regarding the best method for
treatment. Stenoses that do cause chronic ischemia can be treated by endovascular or surgical
approaches with fairly similar outcomes, except that recurrence may be seen more often after
the endovascular approach (240,241). For this reason, some recommend that catheter-based
treatment be reserved for patients with limited life expectancy or medical comorbidities
prohibiting surgery (242). Both modalities require careful follow-up. Patients suspected to have
celiac axis compression syndrome, with no other discernible cause of ischemia, have found
relief after surgical decompression (243).
There are no randomized or controlled trials assessing the efficacy of therapy for acute
intestinal ischemia; recommendations have been derived from retrospective clinical reviews.
Even with aggressive treatment acute mesenteric ischemia is fatal in about 70% of cases
because the diagnosis is often delayed, leading to infarcted bowel and advanced sequelae
(223,224,244,245). Thus, prompt intervention is crucial. There are several isolated reports of
percutaneous intervention to treat thrombotic/embolic causes of acute mesenteric ischemia
(246, 247, 248), however, most cases will require surgery to remove nonviable bowel and
provide revascularization via embolectomy or bypass grafting. Often a second-look surgery is
planned 24 to 48 hours later to remove infarcted bowel that was not recognizable as such at
the time of the first surgery (75). Treatment of nonocclusive acute ischemia from cardiogenic or
septic shock is supportive. If vasospasm from ergots or cocaine is suspected, transcatheter
administration of vasodilators may be of some utility (249).
EXTRACRANIAL CAROTID ARTERY STENOSIS

Etiology
Atherosclerosis is the most common cause of carotid artery disease. The natural history of the
developing plaque is the same as in other vascular beds: increased cellular proliferation, lipid
accumulation, calcification, ulceration, hemorrhage, thrombosis, and thromboembolism. The
carotid artery bulb and bifurcation have complex flow dynamics that lead to low shear stress
and thus a predilection for atheroma formation. Other etiologies of carotid artery disease are
much less common: Takayasu arteritis, giant cell arteritis, FMD (in which the incidence of stroke
is estimated to approach 25%), carotid artery dissection, carotid body tumor, radiation
arteriopathy, and hypercoagulable conditions.
Epidemiology
It is estimated that there are >700,000 strokes in the United States each year (250).
Hypertension is the principal risk factor for both ischemic and hemorrhagic strokes (251), acting
both as a primary etiology and secondarily by promoting conditions such as atrial fibrillation and
myocardial infarction that increase the risk for cerebral embolism. Diabetes also increases the
risk of ischemic stroke two- to sixfold (252). The epidemiological correlation between
cholesterol and the risk of stroke is not as well established as it is for the risk of developing
coronary artery disease. Approximately 85% of strokes are ischemic, and extracranial internal
carotid artery stenosis accounts for 15% to 30% of these strokes (253,254). Patients with
carotid artery stenosis who are at a higher risk of stroke include men and those with a stenosis
>75%, progressing carotid stenosis, or heart disease (255).
Carotid artery stenosis >50% is present in up to 10% of men and 7% of women >65 years of
age (256,257). Risk factors include age, male gender, African American ethnicity, family history,
dyslipidemia, diabetes mellitus, cigarette smoking (258), excessive alcohol intake, and
abdominal obesity (259). Of several risk factors assessed in one study, diabetes was the
strongest single risk predictor of advanced carotid atherosclerosis (260).
Carotid artery disease is a sign of systemic atherosclerotic disease. In fact, patients with
asymptomatic carotid artery stenosis have a higher risk of a cardiac ischemic event than of a
stroke (255). In patients evaluated for chest pain, carotid artery disease is significantly
correlated with severe coronary artery disease (261). Forty percent of patients with RAS
undergoing angioplasty have moderate to severe carotid artery
stenosis (262). The prevalence of carotid artery disease is also high in patients with PADa
routine carotid ultrasound screening of 373 consecutive PAD patients demonstrated that 25%
had carotid artery stenosis severe enough (70% to 99%) that they were considered potential
surgical candidates (263).

Factors that lead to evaluation for carotid artery disease include high-risk patients, suspicious
neurological symptoms, and carotid bruits. Seizures, migraine, and cardiogenic syncope can
mimic the signs and symptoms of cerebrovascular disease. The neurological symptoms that
suggest transient ischemic attack (TIA) or ischemic stroke secondary to carotid artery disease
are focal and typically confined to the territory of the ipsilateral middle cerebral artery. The
pattern of neurological deficits that can develop from left internal carotid artery disease include
right hemiparesis, right hemisensory loss, left monocular visual defects (which, when transient,
is called amaurosis fugax) and aphasia. Symptoms due to right internal carotid artery disease
include left hemiparesis, left hemisensory loss, right eye vision loss, left-sided neglect with
decreased awareness of any left sided deficit, and abnormal visual-spatial abilities. When
paresis and sensory loss do not occur concurrently, or if ataxia is present, ischemia or infarct in
the vertebrobasilar system or lacunar infarcts should be suspected. The neurological sequelae
of extracranial carotid disease result from in situ thrombosis and artery-to-artery
atheroembolism. As a consequence, symptoms often begin suddenly. The severity and focality
of the symptoms may fluctuate as thrombi propagate or embolize distally.
If the patient presents during the symptomatic period, a thorough neurological examination can
help localize the ischemic region of the central nervous system. When the patient presents after
symptoms have resolved (TIAs often last <1 hour), physical findings may be limited. Cardiac,
ophthalmologic, and vascular examinations are important and may provide evidence for the
cardiovascular source of thromboembolism. About 4% of asymptomatic adults have a carotid
bruit. While a carotid bruit is a poor predictor of extracranial carotid artery disease or high-
grade stenosis (264,265), patients with bruits have a threefold greater chance of having an
ischemic stroke (266).
Screening of the general population for asymptomatic carotid artery stenosis is unlikely to be
cost effective and is not recommended. Highly selected asymptomatic patients, for example,
those with carotid bruits, may benefit from screening, however, criteria identifying these
patients have not been established (267). When asymptomatic patients are found to have
carotid artery stenosis, those with moderate lesions (60% to 79%) should be followed at
approximately 6-month intervals to detect disease progression that may be considered for
revascularization (268). Patients with <50% stenosis can be followed up annually. Patients
suffering a TIA or stroke require brain imaging by CT or MR imaging to differentiate between
hemorrhagic and ischemic injury. When symptoms or results from brain imaging raise suspicion
for carotid artery disease, evaluation of carotid artery stenosis can be performed with duplex
ultrasonography, contrast-enhanced MRA, or CT angiography. Discussion of these modalities
for evaluation of carotid artery stenosis is discussed in detail elsewhere in this text. Duplex
ultrasound detects carotid artery stenosis with a sensitivity and specificity of ~95%. However,
ultrasound is less accurate in the presence of extensive calcification, tortuosity, or near-
occlusion, and may overestimate stenosis compared with angiography (269). Duplex ultrasound
followed by MRA as needed has been recommended as a highly sensitive, cost-effective
noninvasive assessment of the severity of carotid artery stenosis (270).
Even in patients with significant carotid artery stenosis, 45% of ipsilateral strokes are due to
causes other than the carotid stenosis, such as lacunar infarcts and cerebral embolism
(271,272). Thus, echocardiography should be included in the initial workup of most patients
presenting with TIA or stroke. Screening for the presence of a hypercoagulable state is not
indicated for most patients with TIA or stroke but may be considered in the young or those with
a family history of unexplained thrombosis.
Prognosis
The degree of internal carotid artery stenosis is the most important predictor of stroke among
patients with extracranial carotid artery disease (273). In the absence of medical therapy,
~25% of lesions <50% progress to >50% within 3 years (265). Hypertension, cigarette
smoking, and diabetes increase the rate of progression (265,274). The average annual risk of
ipsilateral stroke increases from 3% in patients with a 60% to 74% stenosis to 3.7% for those
with a 75% to 94% stenosis, and decreases to 2.9% for those with a 95% to 99% stenosis and
to 1.9% for those with complete occlusion (271,272). The studies that gave rise to these data
were performed prior to the common use of aggressive medical therapy with aspirin, rigorous
blood pressure control, and statins. The presence of collateral vessels modifies stroke risk. The
2-year risk of stroke with severe stenosis in the absence of collateral vessels is two to three
times higher than when collaterals are present (275). The risk of stroke after an episode of
monocular blindness is just 50% of that after a hemispheric TIA, except if the patient has
intermittent claudication or other additional risk factors that are markers for atherosclerosis
(276). Ulcerated, echolucent, and heterogeneous plaques with a high content of lipid or
intraplaque hemorrhage may represent unstable plaques at high risk for embolism (277, 278,
279).
Management
Medical
Current medical management of carotid artery disease is comprised of blood pressure and
glycemic control, reduction of lipids, smoking cessation, and antiplatelet therapy. The evidence
for each of these recommendations is variable in rigor and is derived largely from trials focusing
on treatment for the risk factor, not for carotid artery disease per se. Hypertension, being the
principal risk factor for stroke, has been the most studied. Overall, in 17 randomized trials,
antihypertensive treatment produced a reduction in stroke incidence of 38% (280), with the
Medical Research Council (MRC) Trial investigators finding an absolute risk reduction of 1.4%
over a 6-year follow-up (281). ACE inhibitors and angiotensin receptor blockers may have an
effect on stroke prevention beyond their effect on blood pressure reduction, showing a 25% to
32% reduction in stroke rate compared to placebo (97,282,283). A study of 793 patients
showed that -blockers can reduce the rate of progression of carotid intima-media thickness in
clinically healthy, symptom-free subjects with carotid plaque (284), suggesting that these
agents may have an effect on atheroma development. Although diabetic patients have an
increased risk for stroke, the evidence for reduction of risk by tight glycemic control is weak
(285). However, a recent study of 24 patients scheduled for elective carotid endarterectomy
demonstrated a reduction in vascular inflammation and improved plaque characteristics with the
use of the antidiabetic drug rosiglitazone
(286). Thus, there is continuing interest in determining whether modifiers of insulin resistance
will affect stroke rate. As a major risk factor in the development of atherosclerosis, the plasma
lipid level is a logical target for stroke prevention. To date, most of the studies assessing the
effect of statins on stroke rate were primarily designed to assess patients with coronary artery
disease. There is, however, increasing evidence suggesting that a reduction in plasma LDL of
at least 25% by pharmacological therapy reduces the development of carotid atherosclerosis
and reduces stroke by 30% (90,92,287,288). Treatment with pravastatin has been shown to
decrease the intima-media thickness (289). The Stroke Prevention by Reduction of Cholesterol
Levels (SPARCL) study (290) is the first trial designed to prospectively evaluate the benefits of
lipid lowering on cerebrovascular events in patients who have had a prior stroke or TIA but have
no clinical evidence of coronary artery disease. This trial demonstrated a significant effect of
high-dose statin in decreasing recurrent stroke, first major cardiovascular event, or need for
revascularization. Antiplatelet agents are the central therapeutic modality for the treatment of
patients with transient ischemic attacks (291,292) and carotid artery stenosis (293,294). The
use of aspirin after carotid endarterectomy, at doses of 81 to 325 mg/day, improves outcome
(295, 296). As demonstrated in the Second European Stroke Prevention Study (ESPS-2) and
the ESPRIT trial, the combination of sustained-release dipyridamole and aspirin, compared with
either agent alone, also significantly reduces the incidence of a second stroke (297,298) The
CAPRIE trial compared aspirin to clopidogrel in patients with recent ischemic stroke, recent
myocardial infarction, or established peripheral arterial disease. Overall, clopidogrel reduced
the risk of myocardial infarction, stroke, or vascular death. However, there was no signficiant
difference in outcome between aspirin and clopidogrel in the subgroup of patients with recent
ischemic stroke (70). The combination of clopidogrel with aspirin for secondary prevention of
stroke was not effective in further decreasing stroke risk compared to aspirin alone in the
recent CHARISMA trial, and it did increase the risk for bleeding (115,299).
Revascularization
The indications for surgery depend on the absence or presence of symptoms and the degree of
stenosis. Evidence supporting the benefit of surgery for symptomatic patients with significant
stenoses is fairly well established, whereas the evidence supporting the benefit of surgery in
asymptomatic patients, though present, is less compelling. In any case, the benefits of surgery
in asymptomatic patients are most evident when a low perioperative mortality is maintained,
that is, 3%. The NASCET and ECST studies were designed to assess medical therapy versus
carotid endarterectomy in symptomatic patients (302,303). Patients who derive the greatest
benefit from carotid endarterectomy are those with symptoms attributable to carotid artery
disease and a stenosis 70% (number needed to treat = 6). Surgery in symptomatic patients
with moderate stenoses (50% to 69%) have reduced benefit (number needed to treat = 15-19),
and patients with <50% stenosis do not benefit (302,303). The greatest risk reduction for future
stroke is seen in patients presenting with hemispheric TIA, those with tandem intracranial
lesions or intraluminal thrombus, those without collateral vessels (273), and elderly symptomatic
patients without significant comorbidities (304). Symptomatic patients demonstrating the least
benefit are those with widespread white matter changes, those with symptoms/risks defined
solely by monocular blindness (300), and women with few risk factors (305). The risk of
surgery with contralateral internal carotid occlusion is high (14%), but the risk of stroke at 2
years is much higher (69%) with medical therapy alone (306). Conversely, the benefit of
surgery in the presence of near-occlusion of the ipsilateral artery is muted.
The appropriate treatment for asymptomatic patients with carotid artery stenosis, as opposed
to those who are symptomatic, is a matter of some controversy. For asymptomatic patients,
three major trials showed no benefit of surgery on the primary outcome of stroke regardless of
severity of stenosis (307, 308, 309). Two other studies (the Asymptomatic Carotid Artery Study
[ACAS] [310] and the MRC Asymptomatic Carotid Surgery Trial [ACST] [311]) demonstrated a
5-year risk of stroke or death of 11% to 12% with medical therapy and deferred surgery and a
6% to 7% risk with immediate surgery. It must be noted that these benefits required a
perioperative stroke risk lower than is met in most published trials (312). Nevertheless, these
two studies are used to support carotid endarterectomy in asymptomatic patients with stenosis
of 70%, when the perioperative risk is <3% (250).
Endovascular treatment of carotid artery stenosis is discussed in detail in Chapter 9. To date
there are no definitive studies comparing outcomes with current stenting procedures (i.e., use
of noncompressible stents and embolic protection devices) to surgery in the asymptomatic
patient populations similar to those studied in the ACAS/ACST trials. The SAPPHIRE study
compared stenting to carotid endarterectomy in high-risk patients (clinically significant cardiac
disease, severe pulmonary disease, contralateral carotid occlusion, recurrent stenosis after
endarterectomy, age >80 years) deemed suitable for either surgery or stenting (313). Results
of this study indicated that carotid stenting with the use of an embolic protection device is not
inferior to endarterectomy in high-risk patients. In two recent studies that compared carotid
artery stenting to carotid endoarterectomy for symptomatic carotid artery stenosis, equivalency
of the two procedures with regard to 30-day rates of stroke and death was not demonstrated,
and adverse outcomes were higher in the group treated with carotid artery stents (314, 315).
Issues regarding operator experience and use of distal protection devices may have
confounded these studies. The National Institutes of Health-sponsored Carotid
Revascularization Endarterectomy versus Stenting Trial (CREST) is under way and will further
address this issue for symptomatic stenoses >50% (316).
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> Table of Contents > Section I - Peripheral Vascular Diseases > Chapter 2 - Vasculitides: Inflammatory Diseases of Aorta and
Arteries
Chapter 2
Vasculitides: Inflammatory Diseases of Aorta and
Arteries
Jae Hyung Park
The classification of vasculitis is complicated due to protean clinical manifestations and
nonspecific etiologies. One may classify various vasculitides according to the predominant type
of vessel affected. Vasculitides involving large arteries such as the aorta and its major branches
include disorders such as Kawasaki disease (KD), Behet disease, rheumatoid arthritis,
syphilis, and tuberculosis. However, representative entities involving large vessels are giant cell
arteritis and Takayasu arteritis. The common pathogenic pathways of the two diseases are
cellular immune responses involving T cells, antigen-presenting cells, and macrophages (1,2).
In this chapter, only some selected vasculitides of large and medium-sized vessels, which are
encountered clinically in angiographic evaluation and endovascular intervention of the peripheral
vascular system, are discussed (Table 2-1).
Since a variety of nonvasculitic diseases may mimic systemic vasculitis, the correct diagnosis of
a systemic vasculitis is a challenge to clinicians. Conditions mimicking systemic vasculitis are
cholesterol embolism, atrial myxoma, sarcoidosis, fibromuscular dysplasia,
angioendotheliomatosis, ergotism, and neuroectodermal dysplasia (1,2).
There are several warning signs and symptoms of vasculitis: Fever of unknown origin,
unexplained multisystem disease, mononeuritis multiplex, unexplained inflammatory arthritis,
unexplained inflammatory myositis, unexplained glomerulonephritis, and unexplained cardiac,
gastrointestinal, or central nervous system (CNS) ischemia.
The role of imaging has recently increased in importance in the diagnosis of vasculitides of
large and medium-sized arteries, whereas conventional angiography, which demonstrates
luminal changes and geographic distribution, cross-sectional imaging with sonography,
computed tomography (CT), and magnetic resonance imaging (MRI), reveals mural changes
such as circumferential thickening and contrast enhancement. Another significant advance in
imaging diagnosis is 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for the
assessment of disease activity (3).
TAKAYASU ARTERITIS
Epidemiology and Etiology
Takayasu arteritis has been known as pulseless disease, aortic arch syndrome, nonspecific
aortoarteritis, idiopathic aortitis, reversed coarctation, and Martorell syndrome. The majority of
cases have been reported from Asian and African countries. However, there have been reports
from countries in Europe and America, suggesting its worldwide occurrence.
Its etiology remains elusive more than 100 years after its original description (4). There have
been many hypotheses about the possible relationship between Takayasu arteritis and
rheumatoid arthritis, syphilis, giant cell arteritis, autoimmune etiology, group A streptococcal
infection, and tuberculosis. Some suggest a strong relation between Takayasu arteritis and
tuberculosis, pointing to the higher incidence of tuberculin skin reactivity and history of
tuberculous infection (4). However, no definite immunological evidence has proven this
relationship.
Recently genetic predisposition has been suspected to play a role in the etiology. HLA-linked
genes, B5 and Bw5, were reported to be associated with Takayasu arteritis in Japanese and
Mexican patients. At any rate, an autoimmune mechanism is supported by high levels of -
globulins, circulating immune complexes, failure to detect any etiologic agent in the aortic wall,
and involvement of both the aorta and the pulmonary arteries. The difficulty of proving the cause
of the disease is attributed to the delay of pathological diagnosis until the later cicatricial or
chronic stages (4).
Clinical Findings
Females are predominantly involved, with a gender ratio of 6:1 to 8:1 (depending on race). The
age at onset of Takayasu arteritis is variable, from early infancy to middle age, but usually
occurs at between 10 and 20 years.
There are generally two clinical phases: The preocclusive phase, with systemic constitutional
symptoms, and the occlusive phase, with ischemic symptoms of various organs. Constitutional
symptoms are fever, anorexia, malaise, weight loss, night sweat, and joint pain. Local pulse
deficit and high blood pressure may be found. These symptoms may reappear in the chronic
phase. Occasionally, early symptoms are absent, with manifestation only of late occlusive
symptoms such as diminished pulses, bruits, hypertension, abnormal fundi, and heart failure (5).
Most patients have arterial obstructions, but only a few complain of ischemic pain. This is due
to the gradual formation of arterial obstruction with the development of collateral circulation.
Arterial hypertension may develop due to renal arterial or aortic stenoses. Neurologic signs and
symptoms are variable. Headaches, syncope, and hemiplegia may be observed. Visual
disturbances are related to systemic arterial hypertension. Gastrointestinal symptoms, usually
related to occlusion or stenosis of the celiac and superior mesenteric artery, are rare.
Claudication of the lower extremities may be due to aortic stenosis or direct involvement of iliac
arteries (5).
TABLE 2-1 SELECTED VASCULITIDES OF LARGE- AND MEDIUM-SIZED

PERIPHERAL VESSELS
Large-vessel vasculitis
Takayasu arteritis
Behet disease
Medium-sized vessel vasculitis
Polyarteritis nodosa
Kawasaki disease
Buerger disease
Laboratory Findings
An increase in erythrocyte sedimentation rate (ESR), which reflects disease activity, is the most
frequent finding in Takayasu arteritis. The ESR increases during the early and active stages and
gradually returns to normal as activity decreases. However, it has also been reported that the
ESR is not a consistently reliable marker of disease activity (6). Surgical bypass biopsy
specimens from nine patients with clinically inactive disease showed histologically active
disease in four of them (44%). Mild anemia is found in 25% of patients. C-Reactive protein,
anti-streptolysin O titer, and -globulins are abnormal in one third of patients. Tuberculin test is
positive in a high percentage (80%).
Increased frequencies of HLA Bw52, Cw6, DR7, and DQw2 were observed in patients in Korea
(7). Two risk factors for Takayasu arteritis in the HLA system appear to be Bw52 and DR7 (7).
Recently, an increase in CD8-positive T cell subsets, increased IgG and IgM immunoglobulin
levels, positive autoantibodies such as antinuclear antibodies, antineutrophil cytoplasm antibody
(ANCA), anticardiolipin, and anti--2 glycoprotein I (GPI) antibodies were observed in patients
with Takayasu arteritis, suggesting cell-mediated immunity (8).
Diagnosis
Subjective symptoms of Takayasu arteritis are variable and nonspecific. Pulse deficits may be
the first evidence. The presence of hypertension and an elevated ESR level are also clues.
Premature calcification of great arteries may be found on plain radiographs. Clinical diagnosis is
facilitated by angiography that demonstrates the typical luminal abnormalities of the aorta and
its major branches (9,10). Recently concentric mural thickening of the aorta and arteries
detected in CT, MRI, and sonographic evaluation has been suggested as an early finding of
aortitis, prior to any evidence of luminal encroachment (11, 12, 13, 14).
FIGURE 2-1. Abdominal aortography and CT in a 25-year-old woman with Takayasu

arteritis. Conventional angiography (A) reveals irregular luminal narrowing of the supra- and
perirenal abdominal aorta and proximal stenosis of both renal arteries. An axial view of CT
angiography (B) demonstrates mural thickening with enhancement of the abdominal aorta
at the renal artery level, suggesting active aortitis. A radiolucent ring is seen between the
enhanced lumen and the outer wall of the aorta.
Pathology
Gross Findings
Affected arteries show thickening of the aortic wall, with irregular inner surfaces due to medial
lesions. Intact skip areas are usually present between the lesions. Frequent sites of
involvement are the thoracoabdominal aorta and its major branches (15).
There are two popular classifications to describe the extent of Takayasu arteritis. Nasu
classified the distribution of vascular lesions as follows: Type I (cranial branches), type II
(ascending aorta to aortic arch), type III (abdominal aorta and its main branches) (Fig. 2-1),
and type IV (extensive involvement). Ueda classifications are type I (aortic arch and its
branches), type II (descending thoracic and abdominal aorta), type III (mixed variety of type I
and II), and type IV (involvement of pulmonary artery in addition to type I, II, or III).
Frequent sites of branch involvement are the left subclavian artery, left common carotid artery,
innominate artery and other brachiocephalic branches, and renal arteries. Involvement of celiac
and mesenteric arteries and iliac arteries is less frequent.
Microscopic Findings
Initial active inflammation is of three types: (i) acute exudative, (ii) chronic nonspecific
productive, and (iii) granulomatous. Elasticophagia is also an important finding with active
lesions. The inflammatory process originates in the outer media and a part of the adventitia
through the vasa vasorum. The intima shows reactive fibrocellular thickening in corresponding
areas of medial and adventitial destruction. Subsequently those lesions gradually progress to
scar stage and result in fibrosis.
The lumen of the affected artery may be narrowed segmentally or may result in an aneurysm
(9).
FIGURE 2-2. CT angiography in a patient with active Takayasu arteritis. Transverse view
of chest CT in arterial phase (A) shows concentric wall thickening of descending aorta. In
venous phase (B), a concentric ring of low attenuation and delayed enhancement of the
outer wall are demonstrated.
Imaging Findings
Chest Radiography. In the occlusive phase of Takayasu arteritis, there may be dilatation of
the ascending aorta, cardiomegaly, decreased pulmonary vessels, and rib notching.
Calcification is characteristically linear and occurs in the aortic arch and descending thoracic
aorta.
Angiography. In the early stage of the disease, angiography may be normal, without any
luminal changes. The thickened thoracic aortic wall may be seen as the distance between the
intraluminal contrast medium and the air in the lung. In the late occlusive phase, typical findings
of aortography are luminal changes such as stenosis, occlusion, and aneurysmal dilatation of
the aorta and pulmonary artery and their branches (10,11).
Typically the aorta shows diffuse narrowing. Stenosis may be focal, segmental, or diffuse. The
most frequent sites of stenosis are the descending and abdominal aorta. Aneurysmal changes
are not uncommon. Dilatation occurs most often in the ascending aorta and the right innominate
artery. Combined findings of diffuse ectasia of thoracic and upper abdominal aorta and tapered
narrowing of distal abdominal aorta may produce a rat-tail configuration. Aortic dissection is
rare in Takayasu arteritis. However, it may occur in the late phase or, usually, after surgery or
intervention such as balloon dilatation.
The lesion typically involves proximal portions of the branches. Stenosis and occlusion of
subclavian, common carotid arteries, and renal arteries are frequent (Fig. 2-1).
In occlusions of the thoracoabdominal aorta, the intercostal arteries, lateral thoracic, and
internal mammary arteries are enlarged and act as collaterals. In lower abdominal aorta lesion,
a meandering mesenteric artery appears and lumbar arteries are enlarged. There are many
regional collateral pathways in association with occlusions of the aortic arch branches,
subclavian artery, pulmonary artery, and renal artery.
Mural Changes in Computed Tomography, Magnetic Resonance Imaging, Sonography,
and Positron Emission Tomography Evaluation. Precontrast CT may demonstrate aortic
wall changes. In patients with atherosclerosis, calcifications are usually limited to the intima.
However, full-thickness calcification in patients with Takayasu arteritis may be due to the
transmural nature of this inflammatory disease. The presence of a uniformly thickened,
concentric high-attenuation wall in the aorta and pulmonary artery or the presence of extensive
full-thickness calcification on CT of a relatively young female strongly suggests the possibility of
Takayasu arteritis.
The recent advances in spiral CT techniques demonstrate luminal findings as well as dynamic
information on the wall of the aorta and pulmonary artery including thickening and early and
delayed enhancement of the wall after contrast medium injection (Figs. 2-1 and 2-2). Previous
histologic analysis has shown evidence of vascularization of the tunica media, with capillaries
originating at the transition zone between the adventitia and the media and subsequently fanning
out to incorporate the entire medial layer. The early inhomogeneous mural enhancement seen
on CT may reflect this pathologic finding. High attenuation of the aortic wall is even more
pronounced in the delayed phase, suggesting florid inflammation of the media and adventitia. An
inner concentric ring of low attenuation on transverse images of the aorta during the arterial and
delayed phases likely represents the low attenuation of intima between the enhanced outer wall
of the aorta and the opacified intraluminal blood (Fig. 2-2).
A considerable decrease in mural thickness on CT and MRI following steroid therapy in patients
with Takayasu arteritis has been reported (11, 12, 13, 14). In patients in whom the aortic lumen
looked normal on conventional angiography, transverse images from CT angiography revealed
grossly abnormal thickening of the aorta and pulmonary artery (15).
In MRI, due to the same mechanism as in CT, mural thickening and enhancement are observed
(Fig. 2-3). Mural enhancement on postcontrast T1-weighted imaging reflects hypervascularity
or interstitial accumulation of contrast, suggesting active disease, though histological correlation
is not available yet. Late-phase imaging demonstrates persistent wall enhancement on MRI
(16,17). Aortic wall enhancement, equal to or greater than the myocardial tissue signal, may be
reduced on follow-up evaluation, suggesting improved status after effective treatment.
On sonographic evaluation, one may detect segmental or diffuse circumferential wall thickening,
2 to 5 mm, of hyperechogenicity in active Takayasu arteritis (Fig. 2-4). Other sonographic
findings are decreased arterial distensibility and increased arterial stiffness (3,18).
FDG-PET reveals high uptake in the involved portion of the aorta and its arteries. Though
vascular uptake is not specific for vasculitis, PET is a good screening tool for vasculitis in
patients with fever of unknown origin and is useful for follow-up evaluation for the activity of
known disease (19).
FIGURE 2-3. MRI in a patient with active Takayasu arteritis. Transverse view of T1-
weighted cardiac MRI after contrast injection reveals enhancement of aortic wall thickening
in the ascending and descending aorta and pulmonary artery. (From Choe YH, Han BK,
Koh EM, et al. Takayasu's arteritis: assessment of disease activity with contrast-enhanced
MR imaging. AJR. 2000;175:505-511. Used with permission.)
Conventional Management
Takayasu arteritis can be managed by intensive treatment with steroids and
immunosuppressants such as methotrexate, azathioprine, and cyclophosphamide (20). Long-
term anticoagulation therapy has also been recommended, however, results are inconclusive.
Immunosuppressive agents may bring remission in many patients; however, relapse is common
when prednisone is tapered to dosages of 15 mg/day.
Surgical techniques used for stenoses and occlusions are endarterectomy, resection of the
arterial segment and replacement with graft, bypass of the obstruction, and patch angioplasty.
Surgical and endovascular procedures are best performed in the inactive stage of the disease.
According to the extent of the disease, different surgical options are indicated. For
brachiocephalic lesions, a bypass can be created with a graft from the ascending aorta to the
carotid or subclavian arteries. Patients with diffuse stenosis or occlusion involving the
thoracoabdominal aorta require a bypass graft extending from the proximal descending thoracic
aorta to the distal abdominal aorta. After surgery for atypical aortic coarctation, the overall
cumulative survival rate is 62.3% at 20 years (21). However, life-long follow-up is mandatory.
Recently Weaver et al. reported that primary patency of the renal revascularization at 5 years
was 79% in a series of 33 aortorenal bypass procedures (22).
FIGURE 2-4. Carotid sonography in a patient with active Takayasu arteritis. The
longitudinal scan (A) and transverse scan (B) of color Doppler sonography reveal diffuse
circumferential mural thickening of mild hyperechogenicity with mild luminal narrowing of the
common carotid artery.
GIANT CELL ARTERITIS

The synonyms of giant cell arteritis are temporal arteritis, cranial arteritis, and granulomatous
arteritis. This form of vasculitis affects persons over the age of 50 years. Ninety percent of
patients are over age 60 at onset (23). It is relatively common in the United States and Europe.
Women are affected twice as commonly as men. It tends to involve predominantly branches
originating from the arch of the aorta but may involve other large and medium arteries. The
etiology of this condition is unknown. Because it occurs in old age, one hypothesis is an
autoimmune reaction developed against an altered constituent of the artery wall. Inflammatory
infiltrations are most prominent in the regions of elastic fibers in the artery wall, suggestive of a
cell-mediated autoimmune reaction against aged elastin. However, this has not been proved
experimentally (24).
Clinical Findings
Frequent constitutional symptoms are fatigue, malaise, and weight loss. Confusion and mental
depression may occur. A low-grade fever may be present and fever of unknown origin may
occasionally be the presenting manifestation. Headache is the most common symptom, present
in 60% to 90% of patients. There may be tenderness or nodularity along the course of the
temporal or occipital arteries. Jaw claudication may be relieved by rest. There may be ocular
manifestation such as permanent loss of vision, transient visual blurring, and diplopia. There
may be polymyalgia rheumatica, a clinical syndrome of aching and stiffness in the neck, torso,
shoulder, and hip muscles (25).
Physical examination reveals bruits over large arteries or decreased pulses. Ischemic
symptoms may occur in the limbs, however, gangrene is uncommon.
Laboratory Findings
An elevated ESR of 40 mm/hour (Westergren method) is the most useful test, suggesting
active disease. Normochromic or normocytic anemia is present but the leukocyte count is
usually normal. Other acute-phase reactants such as C-reactive protein are not useful. The -2-
globulin fraction and platelet counts are frequently elevated (25).
Diagnosis
The diagnosis of giant cell arteritis is considered in any older patient who complains of transient
or sudden visual changes, prolonged fever, muscle pain, or headaches. Tenderness along the
course of arteries may be detected on examination of the head, neck, and extremities. A
temporal or occipital artery biopsy is recommended to confirm the diagnosis (25). In contrast to
Takayasu arteritis, the onset of giant cell arteritis is rare before the age of 50 years and more
common in Caucasians. However, blindness may result in both conditions. Notably, ophthalmic
and posterior ciliary arteries are responsible for the ocular ischemia in giant cell arteritis,
whereas obstructive lesions in carotid and vertebral arteries are responsible in Takayasu
arteritis (23).
Ultrasonography, CT, and MRI add to traditional angiography by demonstrating diffuse mural
inflammation of the superficial temporal artery. In patients with fever of unknown origin,
additional MRI examination significantly increased the diagnosis of systemic vasculitis, from 6%
to 26% (19,26).
Pathologic Findings
Chronic granulomatous inflammation is seen on histological examination. Infiltration of
lymphocytes, plasma cells, and histiocytes is noted in the media and adventitia. Multinucleated
giant cells are found in most cases in the disrupted elastic laminae. The inflammation appears
as panarteritis or involves portions of vessel wall. Diffuse fibrous thickening of the adventitia
may develop.
There is a similarity of histopathology between giant cell arteritis and Takayasu arteritis.
However, it is noted that the most intense inflammation tends to appear at the internal elastic
lamina and inner media in giant cell arteritis, whereas the lesion tends to be present in the
adventitia and outer media in Takayasu arteritis (23).
Imaging Findings
Arteriographic findings are long segments of smooth arterial stenoses with areas of normal or
dilated lumen, a tapered occlusion of a large artery, with no evidence of plaque or ulceration,
and major involvement of subclavian, axillary, and brachial arteries (Fig. 2-5). Dilatation of the
ascending aorta may be seen.
In giant cell arteritis, high-resolution duplex sonography may show typical hypoechoic artery
wall swelling in superficial temporal arteries (27). A meta-analysis of the ultrasonographic
evaluation for giant cell arteritis revealed a sensitivity and specificity of the halo sign of 69% and
82%, respectively, compared with biopsy (28).
CT may also demonstrate aortic involvement of giant cell arteritis. In the follow-up evaluation,
CT may reveal complete resolution or improvement of the evidence of mural inflammation after
effective therapy (26).
FIGURE 2-5. Giant cell arteritis of the left subclavian artery in a 56-year-old man. Left
subclavian arteriography shows multiple narrowings (arrowheads) due to giant cell arteritis.
As another noninvasive diagnosis of giant cell arteritis, high-resolution contrast-enhanced MRI

reveals thickening of the vessel wall of the superficial temporal artery and increased contrast
enhancement indicating mural inflammation (29). MRI was able to detect earlier stages of
vasculitis disclosing subclinical aortitis in five of six patients (29). The main signs were vessel
wall thickness and edema and increased mural enhancement on postcontrast T1-weighted
images, similar to the MRI findings for Takayasu arteritis (30).
High uptake in the aorta and brachiocephalic branches on FDG-PET is also helpful in the
diagnosis and follow-up evaluation for disease activity after treatment (31).
The primary purpose of medical treatment of giant cell arteritis is rapid suppression of
symptoms and prevention of blindness. Prednisolone remains the treatment of choice. The initial
dose should be 40 to 60 mg/day of prednisone for about 1 month, then the dose can be
tapered gradually if symptoms have resolved. The anticipated side effects of steroids must be
explained to the patient. The symptoms respond well and the ESR becomes normalized after
steroid therapy. Improvement may be noted even in some patients with intermittent claudication
(32). Therapeutic benefit has been reported with the use of low-dose aspirin to prevent platelet
aggregation (33).
Surgical treatment is occasionally indicated if there is significant aortic valve incompetence,
aneurysmal disease, or aortic dissection and in rare cases with claudication even after
adequate steroid therapy (34,35).
BEHET DISEASE
Behet disease is a multisystemic disorder characterized by recurrent orogenital ulcer, ocular
manifestations, and skin lesions. The disease is most often diagnosed in young adults,
generally in Mediterranean, Middle Eastern, and Asian countries. The etiology of the disease is
obscure. A sequence of immunologic events has been implicated in patients with this disease,
suggesting an autoimmune origin (36).
Clinical Findings
Behet disease is more common in men than in women, by a 2:1 ratio. When confined to
mucocutaneous manifestations, the disease has a relatively indolent course. However, when it
involves the vascular or cerebral system, the course tends to progress rapidly. Blindness
occurs in up to 25% of patients with ocular involvement.
Major arterial and venous lesions occur in 6% to 25% of cases and are a frequent cause of
death. In vascular involvement, a venous lesion is more frequent and arterial manifestations are
less frequent, comprising only 12% of vascular complications in Behet disease. The arterial
lesion, which develops in the aorta and pulmonary artery as well as their major branches, is an
aneurysm in 65% of patients and an occlusion in 35%. Thrombosis can occur in almost any
superficial or deep vein (36,37).
Laboratory Findings
There is no definite laboratory finding. Recently autoimmunofluorescence studies in patients
with a clinical diagnosis of Behet disease have shown deposition of immunoglobulin M (IgM),
IgG, and -1A-globulin in vessel walls. Berlit et al. reported that IgG concentrations of
antiphosphatidylserine and antiribosomal phosphoprotein antibodies were significantly elevated
in patients with vascular Behet disease and are useful as humoral parameters for the
diagnosis (38).
Diagnosis
The clinical diagnosis of Behet disease is essentially based on the presence of multiple
physical signs. Four major criteria have been proposed: Oral ulcer, genital ulcer, ocular
inflammation, and skin lesions such as pyoderma and erythema nodosum. Arthralgias, vascular
diseases, CNS involvement, gastrointestinal disease, and epididymitis are additional findings.
Pathologic Findings
Four types of vascular involvement can be identified: Arterial occlusion, arterial aneurysm,
venous occlusion, and varices. Aneurysm is more frequent than occlusion in arterial involvement
in Behet disease. The most common site of aneurysm formation is the abdominal aorta,
followed by the femoral and pulmonary arteries. Additionally, abdominal aortic aneurysms are
more frequent than the thoracic variety in aortic aneurysm (37).
The leading cause of death in patients with Behet disease is the rupture of a large aortic or
arterial aneurysm (36,37). On microscopic examination of the vascular lesions, there is
fragmentation and splitting of the medial elastic fibers and degeneration of the vasa vasorum
with perivascular round cell infiltration. Histologically, aortitis is seen in both active and scar
stages. Active aortitis leads to destruction of the media and fibrosis, predisposing the patient
for saccular aneurysm (39). Perforation of the arterial wall due to obliterative endarteritis of the
vasa vasorum may result in aneurysm formation or rupture (40).
Imaging Findings
The arteriographic findings of occlusion may mimic those of Takayasu arteritis or Buerger
disease in cases of peripheral obliterative arteritis. The aneurysms in Behet disease are
usually of the saccular type, with a narrow neck, and are often multiple, easily detected by CT
or conventional angiography (Fig. 2-6). Most of the aneurysms are false aneurysms, usually
originated from defects on the posterior or lateral wall of the normal-sized aorta. Almost all
named arteries may be involved in both arterial thrombosis and aneurysm formation. CT or
angiography may show pulmonary artery aneurysms that may cause hemoptysis (41,42).
Corticosteroid therapy, immunosuppression, and, occasionally, fibrinolytic therapy have been
used palliatively in Behet disease, with limited success. Cyclosporine, azathioprine, and
chlorambucil have reduced the frequency of ocular attacks. However, no agents including
steroids have been successful in suppressing the disease completely.
Previously, open surgical repair was the definitive treatment for vascular lesions such as an
aneurysm in patients with Behet disease (43,44). Surgery is available for resection of the
lesions and replacement with grafts. However, there are quite a few reports concerning
recurrence following surgical management in about half of cases (45). Okada et al. reported
their experiences with recurrence in eight patients with long-term follow-up. Four cases (50%)
required a second operation and two of the four underwent a third operation due to recurrence
(45). To suppress possible exacerbation after surgery, adjunctive medical therapy may be
helpful (46). Kalko et al. reported successful surgical interventions such as aortic tube graft
interposition and aortofemoral bypass with immunosuppressive therapy, before and after
surgical intervention, to induce remission (46). To avoid complications stemming from surgical
repair, endovascular insertion of a stent-graft may be a reasonable alternative (47).
POLYARTERITIS NODOSA
Polyarteritis nodosa (PAN) is most common in the fourth through sixth decades of life. Males
predominate, with a 2:1 ratio. PAN affects small and medium-sized arteries of the whole body
(48). Though the etiology of PAN is not known, it is generally presumed that immune complexes
mediate vascular damage. There has been evidence of hepatitis B infection in 15% of patients
with PAN (48). A clear distinction between limited and systemic disease and between idiopathic
and hepatitis B-related PAN should be made, because the pathogenetic mechanisms,
treatment, and prognosis are different according to each entity (49).
Clinical Findings
Clinical presentation of PAN is characterized by an insidious onset. Systemic symptoms such as
fever, malaise, and weight loss are common. According to the organs involved, there may be
mononeuritis multiplex, renal disease, gastrointestinal problems, arthralgias, and hypertension.
Kidney vascular involvement, consistent with vasculitis with microaneurysms of the renal
arteries, may be noted in 75% to 85% of cases. Gastrointestinal involvement, such as ischemia
of the mucosa or the entire bowel wall, may be observed in half of patients and typically
presents with symptoms of abdominal angina. The
most serious complication of the gastrointestinal tract is bowel infarction and perforation.
Congestive heart failure may develop due to cardiac involvement. Less common manifestations
are severe myalgia, stroke, rash, skin necrosis, and orchitis (48).
FIGURE 2-6. Aortic aneurysm due to vascular Behet disease on CT and angiography in a
45-year-old woman. Axial view of CT angiography (A) reveals a saccular aneurysm of the
proximal abdominal aorta. Abdominal aortography (B) shows a multilobular aneurysm of
the proximal abdominal aorta and mesenteric collaterals due to celiac and superior
mesenteric arterial occlusion. After successful application of a stent-graft, an immediate
follow-up CT (C) and a 4-month follow-up CT (D) show resolution of the aneurysm. (From
Park JH, Chung JW, Joh JH, et al. Aortic and arterial aneurysms in Behet disease:
management with stent-graftsinitial experience. Radiology 2001;220:745-750, with
permission.)
Laboratory Findings
There is no specific laboratory finding for PAN. The usual laboratory findings are elevation of
the ESR, mild anemia, and moderate leukocytosis. Other findings are elevated circulating
immune complexes, hypocomplementemia, and positive rheumatoid factor (48).
Diagnosis
The diagnosis of PAN should be based on either pathologic proof of necrotizing vasculitis or
angiographic evidence of microaneurysm. The characteristic arteriographic findings are small
aneurysms of visceral or renal arteries. Though the microaneurysms identified on arteriography
are considered almost pathognomonic of PAN, they may be observed in other kinds of
vasculitis.
Pathologic Findings
The disease is the prototype of systemic vasculitis, a rare condition characterized by
necrotizing inflammation of medium-sized or small arteries without vasculitis in arterioles,
capillaries, or venules, with or without glomerulonephritis.
Imaging Findings
In arteriography, lesions are focal and with skip areas. PAN affects small and medium-sized
arteries of the viscera, kidney, or distal limb. The typical lesions are multiple microaneurysms
and occlusions of small arteries (Fig. 2-7). The diagnosis may be rapidly established by
ultrasound and CT angiography. Ultrasonography may reveal a typical swirling pattern of blood
flow in multiple small arterial aneurysms in the kidney. CT angiography of axial and coronal
maximum-intensity projection images may show multiple intrahepatic and intrarenal aneurysms
(50).
Survival may be increased by steroid therapy in some PAN patients. Cyclophosphamide is an
effective adjunctive in acute
patients. Microaneurysms often regress with steroid and cyclophosphamide therapy (51).
FIGURE 2-7. Renal involvement of polyarteritis nodosa in a 71-year-old man. Selective left
renal arteriography reveals multiple microaneurysms (arrowheads) in the peripheral portion
of the kidney.
The surgical challenge is when gastrointestinal or renal involvement occurs, due to arterial
occlusions or multiple aneurysms. Occlusion of visceral arteries may cause cholecystitis,
appendicitis, bowel ischemia, perforation, infarction, or hemorrhage (52).
CHURG-STRAUSS SYNDROME AND POLYARTERITIS NODOSA

This syndrome has many similarities to classic PAN, including involvement of medium-sized and
small vessels and multiple-target-organ involvement. However, involvement of the pulmonary
circulation is predominant in this syndrome, characterized by adult-onset asthma, and striking
peripheral eosinophilia. Other frequently involved organs are skin, nerve, gastrointestinal tract,
heart, and renal kidneys (48) (Fig. 2-8).
FIGURE 2-8. Renal involvement in Churg-Strauss syndrome in a 50-year-old man.
Selective right renal arteriography reveals multiple variable-sized aneurysms in small
arterial branches.
KAWASAKI DISEASE
Though the cause remains unknown, KD is considered to be of infectious origin, reported first in
Japan in 1967 (53). It is 1.5 times more common in males, and 85% of cases occur in children
<5 years. The reported incidence in Japan is 120 to 150 cases per 100,000 children <5 years
old (54). The annual incidence in the United States is suggested as 4 to 15 cases per 100,000
children <5 years of age (55).
Clinical Findings
The disease primarily affects infants in the first year of life and small children. Typically a child
<5 years of age suffers from fever, rash, and red mucous membranes described as nonscarlet
fever syndrome with desquamation. In the acute stage, the disease manifests as a
mucocutaneous ocular syndrome.
KD starts with a week or more of high fever, followed by conjunctivitis, truncal erythema,
cricopharyngeal edema, cervical adenopathy, and erythema of soles and palms. Later,
arthralgias, dry and cracking lips, and desquamation of involved skin may develop. Aseptic
meningitis, hepatitis, pleurisy, and diarrhea may also occur (56).
KD is self-limited. However, intense vasculitis may develop in some patients. It involves small
and medium-sized arteries and veins and is indistinguishable from that of PAN in adults (57). In
the first month, or 6 to 48 months later, coronary artery aneurysms occur as sequelae in 20%
to 25% of untreated children (58). The coronary artery lesion in the acute phase may progress
to coronary stenosis, causing myocardial ischemia.
Laboratory Findings
There is mild anemia, neutrophilia, a high ESR, and, often, marked thrombocytosis. The findings
are not specific. Biochemical and immunologic evidence suggests endothelial cell activation and
injury. There is increased expression of cell adhesion molecules that increase the recruitment of
immune effector cells on the arterial inner lumen. An increased level of vascular endothelial cell
growth factor may have a role in vessel repair (59,60).
Diagnosis
The six diagnostic criteria for KD proposed by Morens and O'Brien are as follows: (i) fever
lasting >5 days; (ii) bilateral conjunctival injection; (iii) changes of the mucous membranes of the
upper respiratory tract; (iv) changes of the peripheral extremitiesperipheral edema,
peripheral erythema, and periungual desquamation; (v) a polymorphous rash; and (vi) cervical
adenopathy. The diagnosis is confirmed if there is fever in addition to four of the above criteria
(61).
Coronary arteriography may reveal single or multiple coronary aneurysms or occlusion.
Aneurysms of the abdominal aorta and brachial, axillary, iliac, renal, hepatic, and mesenteric
arteries have also been reported.
Pathologic Findings
Stage I, during the first week, is characterized by perivasculitis of the small arteries and
inflammation of the pericardium, myocardium, conduction system, and endocardium. In stage II,
2 to 3 weeks after onset, vasculitis develops in small and medium-sized arteries, with aneurysm
formation and thrombosis. In stage III, approximately the fourth week, myointimal proliferation
may develop in the coronary and other medium-sized arteries. In stage IV, 40 days after onset,
scarring may cause stenosis of arteries (61).
FIGURE 2-9. CT angiography of the coronary artery in a 14-year-old girl with Kawasaki
disease. Volume rendering technique (A) and two-chamber view (B) of cardiac CT reveals
a calcified aneurysm of the proximal anterior descending coronary artery (arrow).
Imaging Findings
Though conventional coronary angiography is indicated to confirm coronary involvement in KD,
echocardiography in the first month is highly sensitive for recognizing aneurysm formation.
Recently CT and MR angiography were also reported to be reliable diagnostic tools, equivalent
to conventional coronary arteriography (62). Both the right and the left anterior descending or
circumflex arteries can be clearly delineated by three-dimensional reformation of cardiac CT or
MRI (Fig. 2-9).
There is no specific treatment for KD. Aspirin suppresses systemic symptoms. Steroids may be
lifesaving for patients with myocarditis and shock, but they have no effect on the incidence of
coronary artery or vascular involvement. However, intravenous high-dose -globulin has a
significant impact on the occurrence of coronary disease. High-dose intravenous immunoglobulin
plus aspirin reportedly lowers the rate of coronary artery aneurysms from 20% to 3% to 5%
(63,64).
Symptomatic or expanding aneurysms may be treated by standard surgical techniques with
end-to-end anastomosis or saphenous interposition grafting.
THROMBOANGIITIS OBLITERANS (BUERGER DISEASE)

Buerger disease is characterized by nonatherosclerotic inflammatory segmental involvement of
small and medium-sized arteries and veins in the upper and lower extremities. This condition is
usually encountered in young males who are heavy cigarette smokers. Though it has a
worldwide distribution, the prevalence in Middle Eastern and Far East Asian countries is higher
than that in Western countries. In a series from India, the disease accounts for more than 50%
of limb ischemia (65).
Though the etiology of this condition is unknown, it has a strong association with smoking (66).
There may be a sensitivity or allergy to some component of tobacco, which may lead to an
inflammatory reaction of small vessels. However, smoking may not be the only factor to induce
the disease, considering its relatively low incidence among the large population of smokers in
the world. Other possible etiologic factors of this disease are genetic predisposition,
immunologic mechanisms, endothelial dysfunction, and abnormalities in coagulation (67,68).
Clinical Findings
The classic presentation of Buerger disease is in a young male smoker aged 40 to 45 years.
Recently the incidence has been increasing in women, perhaps because many more women
smoke cigarettes. The symptom starts as claudication of the feet, the legs, and, occasionally,
the arms and hands. Patients may develop ischemic ulcerations in the distal portion of the toes
and fingers. Two or more limbs are involved in this disease. The incidence of upper extremity
involvement has been reported to be from 15% to 100%.
Sometimes angiography demonstrates abnormalities in limbs that are not yet clinically involved.
An abnormal Allen test to evaluate the circulation in the hands may be helpful. Cold sensitivity
with typical Raynaud phenomenon is common as the earliest manifestation (69,70). Though the
disease affects both arteries and veins of lower and upper limbs, visceral intestinal involvement
is rare (71).
Laboratory Findings
There is no specific helpful laboratory test for Buerger disease. A complete serologic test is
used to exclude other diseases that can mimic this condition.
Diagnosis
The clinical diagnosis of Buerger disease is not difficult when a young male smoker presents
with symptoms of bilateral calf
ischemia. The distal nature of the disease and the involvement of lower and upper extremities
are differential points from atherosclerosis. In the differential diagnosis, the diseases to exclude
are atherosclerosis, emboli, and autoimmune disease. Diagnostic criteria for thromboangiitis
obliterans are (i) a history of smoking, (ii) onset before the age of 50 years, (iii) infrapopliteal
arterial occlusive lesions, (iv) either upper limb involvement or phlebitis migrans, and (v) the
absence of atherosclerotic risk factors other than smoking (72). Recently, a scoring system for
the diagnosis of thromboangiitis obliterans has been proposed. Factors favoring a positive
diagnosis are (i) age of <40 years at onset, (ii) intermittent foot claudication, (iii) upper
extremity symptoms, (iv) migrating superficial vein thrombosis, (v) Raynaud phenomenon, and
(vi) angiographic or biopsy proof. Factors favoring a negative diagnosis are (i) old age, (ii)
female gender or nonsmoker, (iii) singlelimb or only upper extremity involvement, (iv) absent
brachial or femoral pulse, and (v) evidence of arteriosclerosis, diabetes, hypertension, or
hyperlipidemia discovered 2 to 10 years after the diagnosis. The probability of the diagnosis is
obtained from the sum of these factors (73).
Pathologic Findings
There is an inflammatory thrombosis in both arteries and veins, with different histological
findings according to the chronology of the disease. In the acute phase, the lesion is
characterized by acute inflammation of all layers of the vessel wall with occlusive thrombosis
(74). There is infiltration by polymorphonuclear leukocytes with karyorrhexis, or
microabscesses. Intense inflammatory infiltration and cellular proliferation in the thrombus are
distinctive finding of Buerger disease, especially for venous involvement. Another characteristic
is an intact internal elastic lamina. Through the intermediate phase, there is progressive
organization of the occlusive thrombus in both the arteries and the veins, with inflammatory cell
infiltration within the thrombus. In the chronic phase, complete organization of the occlusive
thrombus is seen, with extensive recanalization (corkscrew collaterals), prominent
vascularization of the media, and adventitial and perivascular fibrosis.
FIGURE 2-10. CT angiography of the lower extremities in a 42-year-old man with Buerger
disease. Maximum-intensity projection of CT angiography reveals relatively intact proximal
arteries including iliac arteries (A) and femoral arteries (B). In contrast, multiple occlusions
with corkscrew-type collaterals are present in anterior, posterior, and peroneal arteries of
both legs (C).
Imaging Findings
Arteriography has an essential role in the diagnosis of Buerger disease. The findings are
multiple, bilateral focal segments of stenosis or occlusion, with a normal proximal vessel.
Bilateral infrapopliteal occlusive disease is seen in almost all limbs, with occlusion of anterior
tibial, posterior tibial, and peroneal arteries.
The distribution of the lesions is segmental, with skip areas of normal vessels. The
characteristic arteriographic findings are (i) small and medium-sized vessel involvement, (ii)
segmental occlusive lesions, (iii) more severe disease distally, (iv) collateralization around areas
of occlusion (corkscrew collaterals), (v) normal proximal arteries, and (vi) no source of
embolism (73). Ultrasonography and CT scan may exclude atherosclerotic lesions on the aorta
and the lower limb arteries and confirm the distal occlusions of leg arteries (75) (Fig. 2-10).
The most important therapy for Buerger disease is the complete discontinuation of cigarette
smoking or use of tobacco in any form. It is also important to educate and counsel the patient
to explain the importance of the cessation of smoking (76).
Symptomatic treatment includes foot care, trial of calcium channel blockers, antiplatelet agents,
analgesics to control pain, sympathectomy, bypass surgery if anatomically feasible, and
cessation of smoking. Cellulitis is treated with antibiotics and superficial phlebitis with
nonsteroidal anti-inflammatory agents.
Amputation is utilized only when all else fails. Surgical revascularization is not usually an
alternative due to the diffuse involvement and distal nature of the disease, especially when
there is no vessel available for distal anastomosis. However, if there is a patent distal artery
available for terminal anastomosis, bypass surgery should be considered, with the use of an
autogenous vein.
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> Table of Contents > Section I - Peripheral Vascular Diseases > Chapter 3 - Venous Thromboembolic Diseases
Chapter 3
Venous Thromboembolic Diseases
Michael R. Jaff
Steven Deitelzweig
Venous thromboembolic disease (VTE) is a major cause of morbidity and mortality in the United
States. Identifying the presence of risk factors for VTE is important for raising the index of
suspicion and defining the need for prophylactic measures. Accurate diagnosis followed by
effective therapy unequivocally reduces the morbidity and mortality of pulmonary embolism
(PE).
Deep venous thrombosis (DVT) and PE are generally considered to represent two clinical
manifestations of the same disease. VTE remains an important cause of morbidity and mortality
in the United States. The presentation of DVT is varied; many patients are asymptomatic with
life-threatening conditions, and only one third of patients with proximal DVT are recognized
clinically. The true incidence of DVT may be as high as 2 million patients per year in the United
States. PE causes 10% of all in-hospital deaths and remains the single most important medical
cause of maternal deaths associated with live births in the United States. It is estimated that
600,000 patients develop PE each year in the United States and that 60,000 die of this
complication (1, 2, 3, 4). Unfortunately, autopsy studies continue to show that most cases of
fatal PE are unrecognized and undiagnosed (5).
A serious morbid sequelum of DVT is the manifestation of postthrombotic syndrome (PTS), or
postthrombotic chronic venous insufficiency (CVI), characterized by chronic limb pain, edema,
and ulceration of the lower extremities. Postthrombotic syndrome develops in 30% of patients
within 8 years of an initial DVT and contributes to the substantial cost of management (6).
PATHOGENESIS
Venous thrombi typically form along the valve cusps within the soleal sinuses of the calf as a
result of platelet aggregation and altered venous flow dynamics, and can overwhelm the
endogenous fibrinolytic system within minutes. The propensity of the thrombus to embolize is
greatest in the early or loose phase (first 7 days), when the thrombus is comprised of red
blood cells, white blood cells, and platelets within a fibrin mesh. The thrombus is subsequently
infiltrated by histiocytes and fibroblasts, becoming adherent to the vessel wall. The
organizational process continues through collateralization or retraction, ultimately leading to an
often irreversible, intimal injury during the recanalization phase.
The risk of development of a VTE is directly related to three pathophysiologic factors first
described by Rudolph Virchow in the 19th century and now known as Virchow's triad: venous
endothelial damage, localized or systemic hypercoagulability, and stasis of venous blood.
HISTORY AND PHYSICAL EXAMINATION

The history and physical examination are insensitive and nonspecific for the clinical diagnosis of
both DVT and PE. A number of clinical studies have established that DVT cannot be reliably
diagnosed based on the history and physical examination, even in high-risk patients. Patients
with DVT may or may not experience the classic symptoms of edema, erythema, or pain in the
limb. With the Homan sign (pain with dorsiflexion of the foot) and the Moses sign (reproducible
pain with calf manipulation), two physical examination findings commonly reported by trainees
and ancillary health care professionals, are neither sensitive nor specific for the diagnosis of
DVT. When present, however, any of these findings may merit further evaluation despite their
lack of specificity. Based on controlled clinical trials, clinical suspicion may imply the need for
further evaluation but cannot, by itself, be relied on to confirm or exclude the diagnosis of DVT.
PE should always be considered whenever unexplained dyspnea is present. Dyspnea, pleuritic
chest pain, and hemoptysis are common in PE but are nonspecific. Anxiety, lightheadedness,
sudden hypotension, and syncope are all symptoms that may be caused by PE but may also
result from a number of other disorders. Tachypnea and tachycardia are common signs of PE
but are also nonspecific. The cardiac and pulmonary physical examinations are both
nonspecific. Diagnostic efforts for suspected PE may be appropriate even in the setting of
alternative explanations if risk factors and the clinical settings are suggestive.
Although nonspecific, clinical evaluation is of considerable value in the selection of patients in
whom there is a need for further diagnostic studies. The frequency of specific symptoms and
signs were similar in the PIOPED study whether or not underlying cardiopulmonary disease
was present (7,8).
RISK FACTORS
Risk factors for VTE are increasingly common as the population ages and becomes more
overweight and the prevalence of malignancy continues to rise. Virtually any patient admitted to
a hospital for care of an underlying illness is at risk of VTE (9) (Table 3-1).
Several institutions have adopted VTE risk assessment protocols to systematically identify and
evaluate patients who require prophylaxis. To optimize outcomes, these risk assessment tools
must incorporate current clinical evidence in a manner that is simple to execute and universally
applicable. One novel and effective method is through the use of electronic alerts. In a large
prospective randomized study of hospitalized patients
at risk for VTE, an electronic alert system notified admitting physicians of the need for
prophylaxis against VTE. The control patient physicians did not receive an alert. After 90
days, there was a statistically significant reduction in documented VTE rates among the
patients whose physicians were alerted (10).
TABLE 3-1 RISK FACTORS FOR VENOUS THROMBOEMBOLISM
Surgery
Trauma
Major, lower extremity
Spine
Immobility, paresis
Malignancy
Treatment of malignancy
Prior venous thromboembolic disease
Advancing age (>40)
Pregnancy
Oral contraceptives containing estrogen
Hormone replacement therapy
Selective estrogen receptor modulators (tamoxifen)
Acute major medical illnesses
Chronic medical illnesses
Heart, respiratory failure
Nephrotic syndrome
Inflammatory bowel disease
Myeloproliferative disorders
Paroxysmal nocturnal hemoglobinuria
Obesity
Varicose veins
Central venous catheters
Pacemakers/implantable defibrillators
Inherited/acquired thrombophilic disorder
Source: Adapted from Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous
thromboembolism. The Seventh ACCP Conference on Antithrombotic and Thrombolytic
Therapy. Chest. 2004;126: 338S-400S.
DIAGNOSIS OF DEEP VENOUS THROMBOSIS AND

PULMONARY EMBOLISM
Acute Pulmonary Embolism
Chest Radiography
Most patients with PE have an abnormal but nonspecific chest radiograph. Common
radiographic findings include atelectasis, pleural effusion, pulmonary infiltrates, and elevation of
a hemidiaphragm. Classic findings of pulmonary infarction such as a pleural-based, wedge-
shaped opacity at the costophrenic angle indicating pulmonary infarction (Hampton hump) or
decreased vascularity in a segment of lung distal to a pulmonary embolus (Westermark sign)
may suggest the diagnosis, but they are infrequent. A normal chest radiograph in the setting of
severe dyspnea and hypoxemia without evidence of bronchospasm or anatomic cardiac shunt is
strongly suggestive of PE. Under all circumstances, however, the chest radiograph cannot be
used to conclusively diagnose or exclude PE. Other processes such as pneumonia, congestive
heart failure, pneumothorax, and rib fracture may cause symptoms similar to those of acute PE,
and should be considered. The confirmed presence of musculoskeletal or cardiopulmonary
disease does not necessarily exclude the possibility of acute PE. In the PIOPED study (7), the
chest radiograph was abnormal in 98 of 117 (84%) patients, with the most common
abnormalities being atelectasis and/or parenchymal abnormalities, which occurred in 79 of 117
(68%) individuals. The finding of dyspnea, tachypnea, pleuritic pain, atelectasis, or a
parenchymal abnormality on the chest radiograph was present in 115 of 117 (98%) patients
with PE.
Electrocardiography
The electrocardiogram cannot be relied on for the diagnosis of acute PE. Findings in acute PE
are generally nonspecific and include T-wave changes, ST-segment abnormalities, and left or
right axis deviation. Even with massive or submassive PE, manifestations such as the S1Q3T3
pattern, right bundle branch block, P pulmonale, and right axis deviation occurred in only 26%
of patients. The low frequency of specific electrocardiographic changes associated with PE
was confirmed in the PIOPED study (7). Nonspecific ST-segment or T-wave changes were the
most common electrocardiographic abnormalities, noted in 44 of 89 (49%) patients.
Arterial Blood Gas Analysis

Hypoxemia is common in acute PE. In the PIOPED subset of patients suspected of PE without
pre-existing cardiopulmonary disease, the Pao2 and A-a gradient values were compared (8).
Interestingly, patients with and without PE could not be distinguished based on either of these
values. Although the A-a gradient is usually elevated in PE, it may rarely be normal in patients
without pre-existing cardiopulmonary disease.
D-Dimer Testing
D-Dimer represents a specific derivative of cross-linked fibrin and has been extensively
evaluated in the setting of suspected acute DVT and PE. A normal enzyme-linked
immunosorbent assay (ELISA) appears to be sensitive in excluding PE. When a positive D-
dimer level is considered to be 500 g/L, the sensitivity and specificity for PE have been
shown to be 98% and 39%, respectively (11). However, many clinical conditions in addition to
acute thromboembolism are associated with an elevated D-dimer level. While the sensitivity of
the D-dimer appears high, the specificity is not high enough to be diagnostic.
A negative D-dimer assay, together with a respiratory rate of <20 breaths/minute and a Po2
>80 mm Hg, has proven to be very sensitive in excluding acute PE (12). Symptoms, signs,
radiographic findings, electrocardiography, and the plasma D-dimer assay cannot be
considered diagnostic of PE or DVT. When these entities are suspected, further evaluation with
noninvasive or invasive testing is necessary.
Formal clinical prediction rules have since been created and validated that can help even the
novice clinician determine the pretest probability for DVT and PE. In a recent prospective
clinical trial, the SimpliRED assay was used together with a scoring system utilizing parameters
that were readily available in the emergency department (13).
Cardiac Troponin
Patients with PE sometimes have elevated troponin levels. Elevated troponin is specific for
cardiac myocyte damage, and the right ventricle appears to be the source of the enzyme
elevation in acute PE. Not surprisingly, both cardiac troponin T and cardiac troponin I levels
have been found to be elevated in acute PE and, in particular, in more massive PE in which
myocyte injury due to right ventricular strain might be expected. Several studies have suggested
that troponin levels may be elevated in acute PE (14), and a recent investigation suggested that
an elevated level might be of prognostic value (15). Troponin levels are not sensitive enough to
rule out PE when clinical suspicion is relatively low, without additional diagnostic testing. The
most important application of elevated cardiac troponin levels is that in a clinically compatible
setting, an elevated value might serve as a clue to the diagnosis of PE and lead to further
investigation.
Brain Natriuretic Peptide

Plasma natriuretic peptide levels may be a supplementary tool for evaluating right ventricular
function in patients with acute PE (16). The exact utility is yet unclear and currently under
evaluation.
Ventilation/Perfusion Scanning and Pulmonary Arteriography

Spiral computed tomography (CT) and ventilation/perfusion lung (V/Q) scanning are the most
common diagnostic tests utilized for suspected PE. Based on well-designed, prospective
clinical trials, when the V/Q scan is nondiagnostic, it should be interpreted together with the
index of clinical suspicion (17). In the PIOPED study, the utility of V/Q scanning combined with
clinical assessment of patients with suspected PE was prospectively evaluated (18). Patients
with confirmed PE had scans that were of high, intermediate, or low probability, as did most
patients without PE. Although the specificity of high-probability scans was 97%, the sensitivity
was only 41%. If the clinical scenario suggests PE, the diagnosis of PE should be rigorously
pursued even when the lung scan is of low or intermediate probability. When the V/Q scan is
normal, PE is effectively excluded. A nondiagnostic scan requires further evaluation.
A previous PE or patients with chronic PE may also have high-probability scans. Low- or
intermediate-probability (nondiagnostic) V/Q scans are common in patients subsequently
proven to have PE.
Several potential diagnostic pathways may be appropriate after a nondiagnostic V/Q scan.
Pulmonary arteriography (the gold standard) or CT angiogram should be considered, and a
nondiagnostic V/Q scan may help guide the vessels selected for arteriogram, limiting the
amount of contrast required. Arteriography is considered safe in experienced hands.
In the setting of a nondiagnostic V/Q scan, lower extremity venous duplex ultrasound is a
reasonable surrogate imaging strategy. If this is positive for DVT, treatment can be instituted
and no additional studies are needed. When the ultrasound is negative, PE cannot, however, be
definitively ruled out since the ultrasound is not adequately sensitive when there are no
symptoms or signs of DVT on examination.
Spiral (Helical) Computed Tomographic Scanning

The use of CT scanning for suspected PE has increased significantly over the past decade.
Administration of iodinated contrast via peripheral intravenous route is required for vascular
imaging of the pulmonary vessels. The most common relative contraindications to performing
contrast-enhanced spiral CT scanning are renal insufficiency and contrast allergy. Spiral CT
may reveal emboli in the main, lobar, or segmental pulmonary arteries with >90% sensitivity and
specificity. Three-dimensional reconstruction techniques (multiplanar reformation) can be
applied to the opacified pulmonary vasculature to better define vessels located within the plane
that has been sectioned. Goodman and others (19) have strongly endorsed the incorporation of
CT scanning into diagnostic algorithms for PE. Studies evaluating spiral CT to determine its
sensitivity and specificity for acute PE have revealed a range of 53% to 100% and 81% to
97%, respectively, for these parameters (20). Different study designs, patient exclusion criteria,
levels of experience, and reading protocols have accounted for some of the differences.
The sensitivity for PE in smaller (subsegmental) vessels remains suboptimal, and the
importance of such small emboli also is controversial.
An important advantage of spiral CT over V/Q scanning in suspected PE is the ability to define
nonvascular etiologies for symptoms, including pneumonia, aortic dissection, and
pneumothorax. The cost-effectiveness of utilizing spiral CT scanning for suspected PE has been
studied, and it would appear that because of the frequency of nondiagnostic V/Q scans, spiral
CT scanning may prove to reduce cost in the evaluation of patients with suspected PE (21).
Additional prospective, randomized, clinical trials comparing CT scanning with the standard
diagnostic approach to PE are currently under way. In PIOPED II, sponsored by the National
Institutes of Health, more than 1,000 patients with suspected PE are undergoing V/Q scanning,
spiral CT, lower extremity ultrasound, and pulmonary arteriography to better assess the
appropriate role of the latter modality. A key component of this study is to evaluate the
sensitivity and specificity of CT venography. Previous studies have suggested the potential for
diagnosing DVT, PE, or both with one contrast injection (22). Nonetheless, algorithms for the
diagnosis of PE include clinical probabilities, laboratory testing, and imaging (23).
Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) has been utilized to evaluate clinically suspected PE (24). In
view of the relatively frequent contraindications to CT scanning such as renal insufficiency,
further evaluation of MRI for PE diagnosis is appropriate. Many patients with pre-existing
azotemia are not candidates for iodine contrast-based examinations, therefore providing an
opportunity for MRI of the pulmonary vasculature, including scanning with ventilation and
perfusion phases (25).
Echocardiography
Other diagnostic techniques can sometimes prove useful, particularly in the setting of massive
PE. Echocardiography, which can often be obtained more rapidly than either lung scanning or
pulmonary arteriography, may reveal findings that strongly support hemodynamically significant
PE. Direct visualization of massive PE may occasionally be noted, particularly if
transesophageal echocardiography is performed. Echocardiography is sometimes used to
gauge the extent of right ventricular dysfunction in the setting of proven acute PE (26).
Intravascular ultrasound has been used to directly visualize acute PE at the bedside (27).
Acute Deep Venous Thrombosis

The diagnosis of acute DVT relies on objective testing. Compression ultrasound is by far the
most common technique utilized in the setting of suspected DVT. Impedance plethysmography
has been essentially replaced by ultrasound.
Compression Duplex Ultrasonography

Evidence from multiple, prospective, randomized clinical trials indicate that compression
ultrasound is highly sensitive and specific for symptomatic, proximal acute DVT but insensitive
for asymptomatic acute DVT, as well as isolated calf DVT. The diagnosis of DVT by the
ultrasound technique relies on the lack of compressibility of the thrombosed venous segments,
the appearance of collateral venous flow, and a thrombosed venous segment. More than a
decade ago, the sensitivity and specificity of compression ultrasound for symptomatic
proximal DVT were demonstrated to be well above 90% (28, 29, 30). Limitations were also
recognized, including the insensitivity for asymptomatic DVT, operator dependence, difficulty in
accurately distinguishing acute from remote DVT in symptomatic patients, and insensitivity for
calf vein thrombosis. Ultrasound is relatively inexpensive and is the preferred diagnostic
modality for a straightforward case of symptomatic suspected proximal DVT. In those cases in
which there is a high clinical suspicion for DVT in the face of a negative venous duplex
ultrasound examination, serial ultrasonography is a reasonable strategy (31).
Contrast Venography
Contrast venography remains the gold-standard technique for the diagnosis of DVT, but it is
considered a second-line test for the diagnosis of DVT. It is utilized when noninvasive testing is
nondiagnostic or impossible to perform. It is generally safe and accurate but is an invasive
procedure that may result in superficial phlebitis, DVT, contrast-induced renal insufficiency, or
hypersensitivity reactions (32).
Magnetic Resonance and Computed Tomographic

Venographic Imaging
MRI is being used increasingly to diagnose DVT and may be an accurate noninvasive
alternative to contrast venography. A major advantage of this technique is the excellent
resolution of the inferior vena cava (IVC) and pelvic veins. It appears to be at least as accurate
as contrast venography or ultrasonography for imaging of the proximal deep veins and perhaps
more sensitive for pelvic vein thrombosis. MRI offers the opportunity for simultaneous bilateral
lower extremity imaging and it may accurately distinguish acute from chronic DVT. Newer
techniques have improved the accuracy of MR venography for the diagnosis of DVT (33). Spiral
CT scanning has also been studied for suspected acute DVT. These techniques may fit into
diagnostic algorithms for DVT and PE but at present these algorithms are institution specific,
depending on resources and expertise with certain techniques.
TREATMENT OF VENOUS THROMBOEMBOLIC DISEASE
The goals of DVT treatment are not limited to just prevention of thrombus propagation,
embolization, and recurrence. Today's management must consider re-establishment of venous
patency and prevention of postthrombotic (CVI) syndrome.
Various pharmacologic strategies have been studied, with different efficacy and safety
outcomes, including unfractioned heparins (UFHs), low molecular weight heparins (LMWHs),
warfarin, and several newer agents.
There are two phases in the treatment of patients with symptomatic venous thromboembolism:
Acute (or initial treatment) and chronic (or secondary prophylaxis). Acute treatment options
include continuous intravenous (IV) UFH infusion, subcutaneous (SC) low molecular weight
heparin (LMWH), the use of retrievable or permanent IVC filters, and thrombolytic therapy.
Acute Venous Thromboembolic Disease Management

Antithrombotic Agents
Unfractionated Heparin (UFH).
All heparins are heterogeneous mixtures of glycosaminoglycans derived from animal products
that catalyze the blood enzyme antithrombin. UFH has a narrow therapeutic window and has
been cited as a common cause of drug-related deaths in hospitalized patients. Significant
bleeding occurs in 7% to 30% of patients on IV UFH, and complication rates of 1% to 2% per
day have been reported (34).
UFH prevents extension of thrombus and reduces the risk of subsequent embolization. The
importance of achieving an adequate intensity of anticoagulation with heparin was emphasized
by noting a recurrent VTE rate of at least 29% without therapeutic anticoagulation (35,36).
Raschke et al. reported a weight-based dosing protocol that resulted in a 95% likelihood of a
therapeutic heparin effect, employing an IV bolus of 80 U/kg followed by continuous IV infusion
of 18 U/kg/hour.
Using the activated partial thromboplastin time (aPTT) or another indirect assay (anti-Xa), the
dosage of heparin should be adjusted to maintain an anticoagulant intensity above the lower
limit of a defined therapeutic range (37). In situations where the aPTT is unreliable (i.e.,
circulating anticoagulant, factor deficiency), heparin levels via either thrombin or protamine
titration are useful, aiming for a target of 0.2 to 0.4 U/mL or an anti-Xa level of 0.5 to 1.1 U/mL
as evidence of adequate anticoagulation.
Warfarin, the most commonly used oral vitamin K antagonist in the United States, is the
mainstay of long-term anticoagulant therapy. Warfarin is commonly initiated within the first 24 to
48 hours at a dose of 5 to 7.5 mg/day. The disadvantages of loading doses of warfarin of 10
mg/day have been well described, including a high incidence of supratherapeutic
anticoagulation (36% overshoot phenomenon) at 60 hours, requiring correction (38). Both
heparin and warfarin must be used concomitantly for at least 5 days until the international
normalized ratio (INR) is within therapeutic range (INR = 2-3), preferably for 2 consecutive
days, at which time heparin administration can be discontinued (39). This regimen has been
shown to reduce the incidence of acute hypercoagulability (40). The rationale for this is based
on the short half-life of the vitamin K-dependent factors protein C, protein S, and factors VII, IX,
and X. If oral vitamin K antagonists are initiated while the intrinsic coagulation cascade is not
inhibited, within 8-12 hours, relative protein C deficiency will develop, which is a prothrombotic
state.
The most common and serious adverse effects of any anticoagulant is bleeding. The risk of
major hemorrhage with UFH is higher with intermittent compared to continuous IV infusion. No
difference in major bleeding was detected between continuous IV and SC heparin (41).
Obviously, it is for this reason that close monitoring of anticoagulant effect is critical. When
evaluating risks of anticoagulation-induced hemorrhage, it is undoubtedly the intensity of
anticoagulation that is the strongest predictor (42). Other factors including advancing age,
concomitant antiplatelet therapy, and a history of bleeding are important (43). Healthy patients
have a 2% annual bleeding incidence, while debilitated and severely ill patients have a 25%
annual risk of bleeding. Aspirin is known to increase the hemorrhagic risk when combined with
heparin but has been administered commonly without serious bleeding (44,45).
Bleeding with UFH can be managed by close observation, as the half-life is only 90 min. If
hemodynamic compromise is developing, reversal of heparin effects with IV protamine sulfate is
helpful. The standard dose is 1 mg of protamine for every 100 U of UFH administered.
Protamine sulfate administration must be closely monitored, as serious side effects, including
anaphylaxis, hypotension, and possibly bleeding can occur. It is advised to administer a test
dose prior to full-dose therapy.
A serious adverse effect with all forms of heparin is heparin-induced thrombocytopenia (HIT)
and ultimate thrombosis (HITTS). HITTS is the paradoxical development of thrombocytopenia
and arterial and/or venous thromboemboli in the face
of heparin administration. The incidence of HIT is 3.5% with UFH and 0.6% with LMWH (38).
Although HIT can occur acutely with the first administration of heparin, it classically develops
after at least 5 days of heparin administration. The diagnosis of HIT requires a 50% reduction
in the platelet count compared to pretreatment, or an absolute reduction to 100,000/mm3. This
is an antigen-antibody reaction between heparin and platelet factor 4 (46). There are many
laboratory tests available for confirmation of this disorder; however, given the time delay in
obtaining the results of these laboratory tests and the catastrophic consequences of HIT,
prompt discontinuation of all heparin products must occur at the earliest suspicion of HIT. If this
complication occurs or is suspected, a direct thrombin inhibitor (DTI) such as hirudin or
argatroban needs to be administered because of the potential for cross-reactivity with other
heparins and LMWHs.
Finally, due to an increase in osteoclast activating factor, heparin-induced osteoporosis can be
a serious complication, especially with long-term administration (i.e., the pregnant patient with
pregnancy-induced venous thrombosis in the first trimester). The risk of osteoporosis occurs
less frequently with prolonged administration of LMWH than with UFH (47).
The absolute contraindications to anticoagulant therapy include intracranial hemorrhage, active
internal bleeding, peptic ulcer disease with hemorrhage, malignant hypertension, intracranial
neoplasm, recent and significant trauma or surgery, and a history of heparin-induced
thrombocytopenia.
Low Molecular Weight Heparins.

LMWHs have become primary therapeutic options for patients with acute VTE. These agents
are chemically or enzymatically depolymerized forms of UFH. LMWHs possess a number of
significant advantages over UFH. A prolonged half-life, independent of dose, allows for a
predictable dose response via SC injection once or twice daily, most often without monitoring
(anti-Xa level). LMWHs have fewer pentasaccharide units, the high-affinity binding sites for anti-
thrombin III. The anti-factor Xa:IIa ratio is 1:1 for UFH and from 2:1 to 4:1 for LMWHs (48).
Several major randomized prospective multicenter trials and meta-analyses performed in the
mid-1990s demonstrated a (non-statistically significant) advantage of LMWH over UFH in the
treatment of acute VTE when comparing VTE recurrence, hemorrhage, and mortality.
Leizorovicz et al. examined 2,045 patients in 16 controlled trials and found the trend for VTE
recurrence, bleeding, and mortality favoring LMWH, with respective relative risk ratios of 0.66,
0.65, and 0.72, respectively (49, 50, 51). In addition, several clinical studies have shown
significantly less thrombus progression in patients treated with LMWH compared to UFH (52).
For acute PE, several randomized trials have demonstrated that LMWHs are at least as safe
and effective as UFHs in preventing recurrent emboli (53, 54, 55). Simonneau randomized 612
patients with acute symptomatic PE (not requiring thrombolytic therapy) to the LMWH tinzaparin
SC or UFH IV (31). There was no difference in the primary end points of death, recurrent VTE,
and major hemorrhage at 8 days or 3 months. This composite end point occurred in 2.9% in the
heparin group and 3% in the LMWH-treated patients.
LMWHs have been used as primary therapy for acute venous thromboemboli in the outpatient
setting. Two large randomized trials comparing enoxaparin and nadroparin demonstrated safety
and efficacy in the outpatient setting in specific low-risk patient groups (56,57). When
enoxaparin was administered SC at a dosage of 1 mg/kg twice daily, the investigators found
that 5.3% of the 247 LMWH patients developed recurrent thromboembolism, compared with
6.7% of the 253 patients treated with standard IV UFH (p = NS). In addition, there were no
significant major bleeding rates among the two treatment groups. This study suggests that
LMWH can significantly alter the current therapeutic approach to DVT, allowing patients to be
safely and effectively managed at home and, thus, potentially increasing patient convenience
and markedly reducing health care costs.
Currently, enoxaparin (Lovenox) is approved by the U.S. Food and Drug Administration (FDA)
at a dosage of 1 mg/kg given SC twice daily or 1.5 mg/kg given once daily to inpatients with
DVT with or without PE and at a dosage of 1 mg/kg given twice daily to outpatients with DVT
without PE. Dalteparin (Fragmin) is not yet approved for the treatment of VTE but has been
used at dosages of 100 anti-factor Xa U/kg given SC twice daily and 200 anti-Xa U/kg given
once daily for the management of DVT. Tinzaparin is FDA-labeled at a dosage of 175 IU/kg for
DVT with or without PE. LMWHs have a significant cost and patient convenience advantage
over UFH, but not all patients with VTE should be treated with LMWH in the outpatient setting.
Careful patient selection is the most important component of a successful outpatient treatment
program. Patients without a history of VTE or bleeding who have demonstrated compliance are
excellent potential outpatient therapy candidates. For outpatient acute VTE management,
warfarin therapy should mimic inpatient strategies. Warfarin should be instituted on the first day
of LMWH therapy (58).
Factor Xa Inhibitors (Pentasaccharides).

Fondaparinux is a synthetic analogue of a unique pentasaccharide sequence that mediates the
interaction of heparin with antithrombin. Fondaparinux been approved by the FDA for the
treatment of DVT and PE. It inhibits both free and platelet-bound factor Xa. It binds
antithrombin with a high affinity and is highly bioavailable, with a plasma half-life of 17 hours,
which permits oncedaily administration.
Despite the potential advantage of a prolonged half-life, the lack of reversibility in the face of
fondaparinux-induced hemorrhage has significantly limited the widespread use of this agent.
The drug is excreted unchanged in urine and is contraindicated in patients with severe renal
impairment (creatinine clearance, <30 mL/minute). It does not bind platelet factor 4 and
therefore should not cause HIT.
Another group of drugs that can be used to treat VTE includes the DTIs. Presently, no DTI is
FDA approved for VTE treatment alone. The only oral DTI that has also been evaluated in
phase III clinical trials is ximelagatran. It has a plasma half-life of 4-5 hours and is given twice
daily in fixed doses. It does not have drug and food interactions like warfarin and is renally
cleared. Ximelagatran was rejected by the FDA in 2004 due to concerns about increased
hepatotoxicity and the potential for adverse cardiac events. Other oral DTIs and oral heparin
are in development and the subject of multiple clinical trials.
Newer anticoagulants target individual components of the coagulation cascade and include
heparinoids, oral heparins, tissue factor pathway inhibitors, nematode anticoagulant peptide C2,
and other investigational agents. These agents are at various stages of research and clinical
trials and have the potential to change the paradigm of therapy for acute VTE.
Thrombolytic Therapy
The limitation of standard anticoagulation for VTE has been the lack of restoration of deep
venous patency and preservation of venous valvular function. Therefore, investigation of
thrombolytic agents (commonly used as initial therapy for acute myocardial infarction) in acute
VTE has occurred for more than 30 years. Despite the limited utility of thrombolytic therapy for
DVT and PE, there are three FDA-approved thrombolytic agent regimens for PE utilizing
weight-based strategies. Administrations of these agents for PE commonly are made via a
peripheral IV catheter.
The three FDA-approved regimens for thrombolysis are as follows.
1. Streptokinase: 250,000-IU loading dose over 30 minutes, followed by 100,000 IU/24 hours
IV.
2. Urokinase: 4,400 IU/kg loading dose over 10 minutes, followed by 4,440 IU/kg for 12 to 24
hours IV.
3. Recombinant tissue-plasminogen activator (rt-PA): 100mg continuous IV infusion over 2
hours.
No clear data have demonstrated the superiority of one thrombolytic agent over others. The
aPTT should be measured after the thrombolytic infusion is completed and repeated at 4-hour
intervals until the aPTT is less than twice the upper limit of normal. At this point, continuous IV
UFH should be administered without a bolus loading dose.
The case for thrombolytic use is strongest in patients with massive PE complicated by shock,
which occurs in about 10% of PE patients and for which the mortality rate may be 25%.
Thrombolysis in these patients results in a more rapid resolution of right ventricular dysfunction
due to acute pulmonary hypertension. There is emerging data to suggest that patients with
acute submassive embolism (extensive clot burden without shock or severe hypoxemia) may
also benefit from thrombolysis (59).
The data regarding thrombolytic therapy for DVT are less robust. Most clinicians have
employed a strategy of catheter-directed administration of the thrombolytic agent directly into
the thrombus. There is no agent approved for use by the FDA. Thrombolysis should be
considered in acute massive iliofemoral venous thrombi (<28 days old), as Bjarnason et al. (60)
reported a 66% to 100% lysis rate, compared with only 33% if the thrombus was present for
more than 4 weeks. Theoretically, this will result in preservation of venous valvular function and
a reduced incidence of postthrombotic syndrome (61). Many believe that patients with acute
upper extremity venous thrombosis should also be considered for thrombolytic therapy (62).
Mechanical thrombectomy devices have recently been evaluated for therapy of large occlusive
acute venous thrombi in either the lower extremities or the pulmonary vasculature (63).
Thrombolytic therapy is contraindicated in patients at risk for hemorrhage. Intracranial
hemorrhage is the most devastating complication of thrombolytic therapy and is generally
stated to occur in ~2% of patients. Retroperitoneal hemorrhage may result from a vascular
puncture above the inguinal ligament and is often clinically silent but may be life-threatening.
Malignant hypertension, recent stroke, surgery, biopsy, and arteriotomy of a noncompressible
site are all contraindications to thrombolytic therapy and may offer advantages to the use of
mechanical thrombectomy devices.
Inferior Vena Cava Interruption

IVC filter placement can be performed to minimize the risk of PE from lower extremity deep
venous thrombi. The primary indications for IVC filter placement include absolute
contraindications to anticoagulation or recurrent embolism while receiving therapeutic doses of
anticoagulation. Filters can also be placed in the setting of massive PE when it is believed that
any further pulmonary emboli might be lethal. A number of filter designs exist and can be
inserted via the jugular or femoral veins. Recently, retrievable filters have been approved for
use in the United States. A retrievable IVC filter can be left indwelling as a permanent device, or
it may be retrieved when the clinical need for mechanical IVC interruption no longer exists. The
ideal scenario is a young patient with major closed head trauma, where anticoagulation is risky.
Once the patient recovers from the trauma, retrieval of the IVC filter is desirable. There are
complications of IVC filters, including insertionrelated complications, filter migration, direct
thrombus extension through the filter, and IVC thrombosis. In addition, although IVC filters are
effective in reducing the risk of PE, there is an increased long-term risk of DVT formation (64).
Given the apparent long-term risks of IVC filters, appropriate indications must exist, and
standard anticoagulation should still be the mainstay of therapy (65).
CHRONIC VENOUS INSUFFICIENCY

CVI is an important manifestation of DVT. Although very common, it is often overlooked by
primary care practitioners and cardiovascular specialists alike, viewed as a nuisance rather
than an important chronic illness. Although some define CVI as venous varicosities, the more
serious manifestations of venous stasis ulceration (affecting 0.3% of the adult population) (66)
require more meticulous care. CVI occurs in 92 per 100,000 hospital admissions, 55% being
women, with a length of stay of 7 days (67). Patients with severe manifestations require
repeated physician office visits and hospitalizations, resulting in loss of productivity and reduced
quality of life (68). Patients who recover from acute DVT often suffer from reduced quality of
life early after initial therapy (69). Limb amputations are uncommon but may occur in as many
as 1.2% of patients (67).
CVI is a result of malfunction of the normal venous physiology and anatomy. In normal states,
the superficial and deep veins of the lower extremities work against gravity and variable
intrathoracic/intra-abdominal pressure to propel deoxygenated blood to the right side of the
heart. There are multiple communicating veins that traverse the fascial planes in the thigh and
calf. Each of these deep and superficial veins have multiple one-way venous valves that work
in concert with the calf muscle pump action to aid in the appropriate emptying of blood from the
lower extremities. When these valves become dysfunctional, due predominantly to primary
valvular processes (rare) or following venous thrombosis (common), venous blood tends to
follow the impact of gravitational forces, allowing venous blood to flow into the lower limb. This
results in significant venous hypertension, as emptied venous blood rapidly flows in a retrograde
direction into the lower limb.
Formal definitions of the presence and severity of CVI have been proposed by multiple groups.
The most widely accepted is the CEAP (Clinical, Etiology, Anatomic Location, and Pathology)
classification (70) (Table 3-2). In those patients who develop the most advanced manifestations
of CVI, pathophysiology is thought to be due to vascular inflammation and leukocyte activation
triggered by venous hypertension, ultimately resulting in stasis dermatitis and ulceration (71).
The diagnosis of CVI requires knowledge of both the clinical and the objective hemodynamic
and physiologic manifestations of the disease. Clinical evidence of venous telangiectasias,
reticular veins, and venous varicosities is important to note. Pigmentation of the distal medial
aspect of the calf, lipodermatosclerosis, and atrophie blanche (hypopigmentation of the skin at
an area of prior ulceration) suggest advanced CVI. Frank venous stasis ulcers have a
characteristic location, commonly over the medial malleolus of the ankle, at the area of greatest
venous hypertension. The ulcer is often moist, beefy red, and relatively painless. Without
appropriate therapy, these ulcerations may have significant exudates on the surface.
Bedside tourniquet tests may be helpful in determining whether venous reflux is predominantly
due to superficial, deep, or combined locations (72).
The differential diagnosis of CVI is often similar to that of limb edema, requiring the clinician to
consider local (lymphedema, lipidema, ruptured popliteal [Baker] cysts) and
systemic (congestive heart failure, renal, hepatic dysfunction) etiologies for edema. When
ulceration is noted, the differential diagnosis requires differentiating arterial, venous, and
neurotrophic etiologies.
TABLE 3-2 THE CEAP CLASSIFICATION FOR CHRONIC VENOUS

INSUFFICIENCY
Classification Clinical description
Clinical 0. No venous disease
1. Telangiectasias
2. Varicose vein
3. Edema
4. Lipodermatosclerosis/hyperpigmentation
5. Healed ulcer
6. Active ulcer
Etiologic
Congenital Present since birth
Primary Undetermined etiology
Secondary Associated with postthrombotic/trauma
Anatomic
distribution
Superficial Great/short saphenous veins

Deep Cava, iliac, gonadal, femoral, profunda, popliteal, tibial,
muscular veins
Perforator Thigh/calf perforating veins
Pathophysiology
Reflux Axial and perforating veins
Obstruction Acute/chronic
Both Valvular dysfunction and thrombus
Objective testing often begins with venous duplex ultrasonography, which provides a definitive
diagnosis of acute or remote venous thrombus, as well as a detailed venous map of segments
of venous valvular incompetence. Duplex ultrasonography includes B-mode gray-scale imaging
and compression maneuvers to determine venous patency and Doppler interrogation with
multiple maneuvers to determine valvular function. Doppler imaging demonstrates the direction
of venous blood flow, with any flow toward the foot confirming reflux through incompetent
valves. A valve reflux time >0.5-1 seconds is diagnostic of reflux, with longer reflux times
suggesting more severe reflux (73). Consensus regarding the performance of venous duplex
ultrasonography for assessment of venous valvular incompetence has been reached (74).
In studies of women with venous varicosities, reflux occurred in 80% of cases (75). Sixty
percent of women had reflux of the great saphenous vein alone, while 17% demonstrated reflux
of both the great and the short saphenous veins. This illustrates the need for complete venous
mapping of the lower extremity to determine the likelihood of successful therapy. Interestingly,
most of the cases of great saphenous reflux (88%) had a competent saphenofemoral junction.
Of great importance, the finding of incompetent perforating veins heightened the risk of
increasing CEAP scores (76).
Air plethysmography (APG) is an important diagnostic test that provides physiologic information
regarding the location and severity of CVI. This noninvasive test utilizes changes in limb volume
by determining air displacement in the limb. APG can accurately assess obstruction, venous
refill, and poor calf muscle pump function (77). APG is also very helpful in demonstrating clinical
benefit after venous surgery for advanced CVI (78).
Treatment of CVI is based on basic tenets:
Prevention with aggressive management of acute proximal venous thrombosis
Optimization of skin care (if no ulceration) to provide moisture to often dry, cracked skin
Optimization of wound care, maintaining a moist, clean environment
Reversal of venous hypertension
Weight loss
Aerobic (avoid isotonic) exercise
Patients who present with acute proximal DVT are commonly managed with standard
anticoagulation. However, given that DVT results in CVI in a large proportion of patients within 3
years of diagnosis, intervention with catheterdelivered thrombolytic therapy may result in
prevention of venous valvular dysfunction and CVI (79). Catheter-directed thrombolytic therapy
resulted in preservation of venous valvular function in 44% of patients compared to only 13% of
patients who received systemic thrombolysis (61).
Compression therapy and weight loss remain the two most important maneuvers to reduce
venous hypertension. Depending on the severity of the CEAP score, varying degrees of
compression garments may be used, ranging from 20 to 50 mm Hg. If patients remain
compliant, clinical improvement will occur in the majority of patients (80). In fact, compression
therapy and meticulous wound care for venous stasis ulcers will result in healing in 93% of
patients (81).
Predominantly outside the United States, flavonoids have been used to improve venous tone
and increase venous return in patients with advanced CVI (82). Some have advocated the use
of pentoxifylline for those patients with venous stasis ulcers (83).
If conservative measures fail, or the patient cannot remain compliant, invasive therapy is often
required. Patients with CEAP scores of 4-6 will commonly require some form of invasive
intervention. Invasive therapy ranges from injection venous sclerotherapy using duplex
ultrasound guidance (84), endovenous ablation of venous varicosities with radiofrequency (85),
laser (86), or venous (87) surgery. The most common surgical treatment is removal of the great
saphenous vein with high ligation at the level of the saphenofemoral junction, resulting in a
dramatic improvement of symptoms and promoting healing or recalcitrant venous ulcers (88).
In situations where incompetent venous perforating veins result in nonhealing of venous stasis
ulcerations, ligation of these perforators is required. Recent advances in technique and devices
have led to the development of a less invasive procedure, subfascial endoscopic perforator
surgery, which promotes healing of these difficult venous ulcerations (89).
Although surgical venous valvuloplasty has been performed with reported reasonable success
(90), this procedure is limited to very few centers worldwide. Recent attempts to develop
percutaneous venous valves to restore venous competency have been fraught with serious
limitations including thrombosis, malalignment, and incompetence.
CONCLUSIONS
VTE is a common problem, felt to represent the major cause of mortality in hospitalized
patients. A high clinical index of suspicion is required in at-risk patients, as symptoms may often
be absent or minimal. Diagnostic algorithms for both DVT and PE must be center-specific,
based on the available expertise and timeliness of the diagnostic tests. Once the diagnosis has
been confirmed, appropriate therapy is required in the acute stage to prevent thrombus
propagation and embolization. In patients
with profound manifestations of VTE, thrombolytic therapy should be considered.
CVI, a common complication of DVT, represents more than a nuisance to most patients. There
is a significant reduction in quality of life, requiring frequent physician visits, potentially
cumbersome wound care, time away from occupations and families, and, on occasion,
hospitalization for infection. Early identification and appropriate therapy are required to prevent
serious complications.
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> Table of Contents > Section II - Vascular Imaging > Chapter 4 - Angiography
Chapter 4
Angiography
Michael A. Bettmann
Angiography involves many diverse components. The focus of this chapter is the factors that
form the basis of this widely utilized imaging and interventional tool, ranging from general
background considerations and history of the field, to major equipment that is utilized, to
ancillary equipment such as catheters, guide wires, and stents, and, finally, to drugs and
contrast agents that are central to the procedures.
It is difficult to trace the development of angiography in a precise and linear way. The initial use
of x-rays after Roentgen's description in 1895 was for the diagnosis of fractures. Within a year,
however, the first angiogram was done, with the injection of contrast into the artery of an
amputated hand (1). Much of the early work on the development of contrast agents, as detailed
in a later section of this chapter, focused on visualization of the urinary tract with an intravenous
injection. Early in the twentieth century, however, it became clear that visualization of arteries
and veins could provide important information for diagnostic purposes and to help guide
therapy. Roentgen received the first Nobel Prize in Medicine for his description of x-rays. The
first vascular study in humans was performed by Franck and Alwens in 1910, with the injection
of a small amount of Lipiodol (ethiodol; Guerbet, France), a poppy seed oil derivative that, in an
emulsified form, is still in wide use today in chemoembolization (2). They injected a small
amount of this oil into dog veins and then into a human antecubital vein, without ill effect. In
1923, Berberich and Hirsch performed the first arteriograms and venograms in humans, utilizing
strontium bromide, with satisfactory visualization but fairly marked pain (3). In 1924, Brooks
performed a peripheral arteriogram in a human using a sodium iodide solution, with very good
anatomic delineation but, still, unacceptable toxicity (4). In the late 1920s, Egas Moniz, a
Portuguese physiologist, neurosurgeon, and diplomat, developed one of the safest and most
widely used of the early contrast agents, Thorotrast (thorium dioxide). He subsequently had a
brilliant career and received the 1949 Nobel Prize in Medicine and Biology, although the Prize
was actually awarded for his description of the prefrontal lobotomy, surgery that has been
totally discredited since (5). Unfortunately, Thorotrast had a similar fate. Although it was
remarkably well tolerated and safe during and immediately following injection, it was an
emitter. It became obvious after a few years of use that, as it was taken up in the
reticuloendothelial system and had a very long biological half-life, it led to a high incidence of
hepatic and other malignancies, and it was removed from the market (6,7).
Vascular access utilizing a cutdown subsequently became fairly widely used, with much of the
original work done by the German surgeon Werner Forssmann, who performed many
catheterizations of himself, including the first catheterization of the human heart (8). This
approach to angiography was clearly limited by the need for a surgical cutdown. After
Roentgen, arguably the single greatest advance in cardiovascular radiology was the
development by Seldinger of a percutaneous technique for vascular access (9) using a hollow-
core needle and guide wire. At the time of the description in 1953 of what became known as
the Seldinger technique, Sven Ivor Seldinger was a junior fellow in radiology in his native
Sweden. He subsequently practiced as a general radiologist for many years in rural northern
Sweden. The importance of this technical advance was rapidly recognized, but the true value of
Seldinger's individual contribution was not appreciated for many years. It led to the
development of diagnostic angiography, in concert with the subsequent development of tools
and techniques by many individuals, for example, the cardiac catheters and techniques
developed by Melvin Judkins, a radiologist who spent most of his career at Loma Linda
University (10). Among the many individuals who made significant contributions to the
development of diagnostic and interventional angiography, arguably the two who made the
greatest contributions were Drs. Charles Dotter (Judkins's teacher and collaborator) and Kurt
Amplatz. Beginning more than 50 years ago, as a young immigrant radiologist in Minnesota,
Amplatz's inventions impacted almost all of angiography. They ranged from many different
types of catheters to film changers that facilitated vascular imaging. His advances continue: the
Amplatzer device is now widely used for the closure of atrial and ventricular defects (11).
Dotter is widely accepted as the father of interventional radiology, but his contributions go
beyond this. He was a remarkably wideranging and creative innovator. With Judkins he helped
to develop selective catheters that facilitated diagnostic coronary angiography. He also worked
closely with William Cook, the founder of Cook, Inc., to develop many of the early catheters
and guide wires that to a very substantial extent form the basis for current equipment. Herbert
Abrams, then at Stanford, was the first to describe biplane image amplified cine angiography
(12), with a colleague was the first to perform percutaneous selective coronary angiography
(13), and was perhaps the first to use interventional techniques, when he described the use of
epinephrine to distinguish malignant from benign vascularity in renal neoplasms (14). Dotter was
the first to consider angioplasty to open stenotic or occluded arteries without open surgery
(using sequentially tapered catheters that were advanced through arterial occlusions) (15),
intra-arterial thrombolysis (16), and vascular stents (17). Other major advances in angiography
and medicine in general came from many radiologists (18). These include Dotter's collaborator
Joseph Rosch, the first to develop TIPS (19,20), Sidney Wallace from M. D. Anderson Cancer
Center, who, with his collaborators, developed vascular occlusions coils (21), and Julio Palmaz,
who was the first to develop a viable intravascular metallic stent (22,23). There are too many
individuals who have made substantive contributions to the field, with either technical advances
or new clinical applications, to allow a complete list. Many have been recognized by catheters
or devices named for them. It is important to recognize the extraordinary originality and
foresight that continues in the field of cardiovascular and interventional radiology.
IMAGING EQUIPMENT
High-quality imaging of vascular structures with x-ray equipment is obviously essential to
angiography. There has been tremendous progress with major x-ray equipment in several
areas. Initially, to image the vascular system, the x-ray tube, the x-ray film, and the table were
all fixed. To image different areas, the patient had to be moved. This was obviated when
moving table tops became available. Subsequently, the tube and the film became movable, with
the surprisingly recent development, in the 1970s, of ceiling or floor-mounted C-arms or U-arms
(Fig. 4-1). Coupled with moving tabletops, this allowed imaging of multiple areas using complex
angles, crucial to evaluating overlapping vessels, such as below-knee arteries. Portable and
fixed units are currently available. Although portable units have certain obvious advantages
(e.g., increased mobility, decreased cost of both acquisition and installation), there are
compelling reasons for the use of fixed units whenever possible. Portable C/U-arms generally
have very limited ability to alter the tube image distance, have limited shielding, and have
relatively small fields of view, with small image intensifiers. This results in a marked increase in
exposure to both the patient and the operator and resolution that is limited and often
suboptimal.
Until the development of the image intensifier in the 1940s (24,25), fluoroscopy had limited
resolution, with poor image intensity (requiring a darkened room and the use of red goggles), a
very small field of view, and very high radiation to both the patient and the operator. The image
intensifier markedly broadened the applicability of fluoroscopic procedures, including
angiography. Relatively small image intensifiers (e.g., 6 to 9 inches in diameter) are appropriate
for many uses, such as cardiac catheterization and coronary angiography, and other, larger
image intensifiers with limited movement (rather than being mounted on movable C- or U-arm
stands) are suitable for fluoroscopy of the abdomen. For angiography, however, it has been
found that 40-cm-diameter (16-in.) field-of-view image intensifiers with movement possible in
three directions are preferable for adequate abdominal coverage as well as for imaging of the
lower extremities, particularly in tall and large patients. The large area of coverage helps to limit
radiation exposure to the patient and to the operator (fewer exposures are necessary to
visualize a large area) and, also, improves the efficiency of performing studies and
interventions. The continual improvement in technology has been so rapid that over the last
three decades an angiography suite becomes substantially outdated within 7 to 8 years. The
evolution from film-screen angiography to digital subtraction angiography (DSA) that began in
the early 1980s was a further major advance (26,27). Rather than exposing standard x-ray film
in some type of multifilm changer, then removing it and putting it through a developer, a process
that is inherently relatively expensive and time-consuming, DSA consists of conversion of the x-
ray image on the receiving phosphor to a digital image that can be reviewed immediately,
digitally processed and postprocessed, and then printed to film or otherwise archived as
necessary. Although subtraction is not a necessary component of this, it was found that utilizing
a computer to subtract a precontrast image from a contrast-containing image improved overall
utility (Figs. 4-2 and 4-3). The inherent spatial resolution of digital imaging is perhaps slightly
diminished compared to film-screen resolution, but the temporal resolution is improved, making
DSA preferable overall.
FIGURE 4-1. Biplane angiography suite with 40-cm image intensifiers on both the frontal
and the lateral planes. The frontal plane is floor mounted and the lateral plane is ceiling
mounted. (See the color insert.)
The next major technological development was direct digital imaging using flat-panel technology.
The temporal resolution with flat-panel technology is in general equal to that achieved with
digital angiography, and the spatial resolution
(depending on the specific technology of the panel itself and of the imaging chain) is usually
equal or superior to that of film-screen angiography (28,29). Another major advantage to flat-
panel technology is that, although the tube is essentially unchanged, the image intensifier is
eliminated. The imagereceiving component of the unit, the flat panel itself, is smaller and more
compact, allowing easier access to the patient during interventional procedures and improved
mobility of the U-arm around the table (Figs. 4-4 and 4-5). Whether or not flat-panel technology
will replace image intensifiers completely is not yet clear, but it is likely that this will occur, for
several reasons. First, flat-panel technology allows direct digital imaging, without the
intermediate step of analogue-to-digital conversion or any requirement for film. This is
congruent with the overall aim of improved efficiency in imaging. Second, as with most (if not
all) major technical advances, the acquisition cost of a flat-panel, direct digital imaging
angiography unit is likely to be greater than that for a film-screen unit, but the overall efficiency
of the system also increases, potentially leading to decreased utilization costs. That is, there is
potentially faster patient throughput, elimination of the need for analogue-to-digital conversion,
elimination of all film and developing costs, and therefore more efficient postprocessing and
archiving of imaging studies, generally to picture archiving and communications system (PACS)
directly. Finally, the use of direct digital imaging facilitates an overall decrease in radiation, to
both the patient and the operator, a factor that is of increasing importance as the population
ages and reliance on image-guided evaluation and intervention increases (30).
FIGURE 4-2. A: Unsubtracted view of selective posterior tibial artery injection in a young
male with a painful heel. Note the faintly seen arteriovenous malformation. B: Subtracted
view of same image shows improved visualization of the arteriovenous malformation.
FIGURE 4-3. Unsubtracted (A) and subtracted (B) views of selective renal arteriogram s/p
embolization for posttraumatic bleed. Note subtraction of the residual extravasated
contrast in (B) as well as the imporoved definition of renal parenchyma.
FIGURE 4-4. Illustration of a flat panel. (See the color insert.)
FIGURE 4-5. Single-plane, ceiling-mounted flat-panel angiography suite. Note the improved
patient access because of the smaller imaging chain. (See the color insert.)
TECHNIQUES AND TOOLS OF THE TRADE: NEEDLES, GUIDE

WIRES, SHEATHS, CATHETERS, AND CLOSURE DEVICES
As with other angiographic equipment, there have been dramatic changes and advances in
catheters, guide wires, and associated equipment since angiography was first used clinically in
the 1930s. As noted, angiography was first performed by gaining vascular access with a
surgical cutdown, a process that was somewhat complex and had significant associated
morbidity. The development of the Seldinger technique allowed angiography to burgeon. Major
changes in catheter materials, performance characteristics, shapes, and sizes have
subsequently allowed the field to evolve dramatically, as have changes in guide wire technology.
Over time, the wall thickness and therefore the necessary outer diameter of catheters have
gradually decreased. Until the 1970s, most catheters were 6 Fr or larger. Parenthetically, it is
important to note that catheters are always referred to in French size, with each increment
equal to 0.33 millimeter. The genesis of this universally used term is not clear. Guide wires, in
contrast, are always classified in fractions of an inch (e.g., a standard 0.035-in. guide wire).
The initial catheters developed between Seldinger's publication in 1954 and the mid-1970s
consisted of straight tubing made out of various plastics, which was cut to length and shaped
over
steam or a gas flame to meet the specific needs as defined by individual angiographers. With
time, it became obvious that certain shapes were particularly useful. Prime examples of this are
the Judkins right and left coronary catheters, developed by Judkins for selective coronary
angiography in the late 1960s and still in use today (10). Other common shapes have come and
gone, often named after the individual radiologist who developed the specific shape. The
specific plastics used have also evolved. A great deal of work, by individuals and companies,
was devoted to use of different polymers and of various coatings to develop catheters that
were smaller and less thrombogenic but had improved torque control and flexibility. Since the
1990s, thrombogenicity has been a minor concern, because of the nature of the polymers used,
the smaller size relative to what has been used in the past versus the size of the vessel, the
smooth nature of both the inner and the outer surfaces, and the increased use of ancillary
medications. Another factor that has played a role in the improvement of catheters is the
hydrophilic coating that is available with many types of catheters.
The use of sheaths has also improved the usability of catheters. Placement of an arterial or
venous sheath avoids some of the trauma to the vessel wall that may occur when catheter
exchange is necessary (31). Also, in manipulation of a catheter, there is generally less friction
to inhibit movement of the catheter tip when a sheath is used than there is when a catheter is
placed directly through skin and subcutaneous tissue. Catheters for interventional use as well
as guiding catheters are discussed in chapters concerning specific interventions. It is worth
noting, however, that vascular sheaths are referred by the French size of the inner diameter,
whereas guiding catheters are referred to by their outer diameter. That is, a 6-Fr arterial
sheath has an inner diameter large enough to accommodate a 6-French catheter. Its outer
diameter will be larger, by as much as 2 to 4 Fr (0.67 to 1.33 mm), depending on the material
used. A 6-Fr guiding catheter has a 6-Fr outer diameter, and therefore its lumen may
accommodate only a 5- or even 4-Fr catheter, again as a function of the specific material used.
Additionally, there may be some minor variations among manufacturers, despite the general
specifications, so it is always useful to look at the label on the packaging prior to opening either
a sheath or a guiding catheter, to ensure that a given-size sheath or guiding catheter will
accommodate a specific diagnostic or interventional catheter.
Guide wire diameters that are commonly available range from approximately 0.012 to 0.045 in.
The basic safety wire consists of an inner core that is a stainless-steel alloy, wrapped with a
smaller wire mandrel that continues for a variable distance beyond the tip of the core. The tip of
the core is attached to the tip of the wire wrapping by a very small safety wire, to prevent
separation. The stiffness of the tip of the wire depends on the characteristics of the wrapping
as well as on the distance from the tip of the core to the tip of the wire as a whole.
The common designations include description of the diameter of the J shape at the end of the
wire (ranging from the narrow 1.5-mm, to the widely used 3-mm, to the relatively floppy 15-mm
J). Additionally, there are straight wires with varying tapers and varying lengths of floppiness.
The overall stiffness of the wire depends on the nature of the core and the wrapping, and
ranges from the usual J-wire, which is moderately stiff, to the several Amplatz wires, which are
available with stiffness ranging from moderate to marked, to a Lunderquist wire, often referred
to as a coat hanger, which is essentially a stiff piece of steel alloy with a relatively floppy distal
piece attached and a Teflon coating.
There is tremendous variation in microcatheter and microwire systems. Although catheters as
small as 3 Fr in diameter have been available for many years, developments with polymers
over the last decade have allowed the catheters to be smaller in overall diameter with thinner
walls, which are nonetheless able to resist higher pressure (and, therefore, tolerate higher flow
rates), with a radiopaque marker made of a band of tantalum or another metal at or near the
tip. Much of the evolution in microwires came subsequent to the development of the steerable
angled glide wire by the Terumo company in the late 1980s (32,33). This guide wire consists of
a Nitinol core (a nickel-titanium alloy with thermal memory that is widely used in medical
devices), covered with a polymer that forms a patented hydrophilic coating. This design
prompted the development of many additional steerable guide wires of various sizes. The
availability of relatively stiff and steerable micro-guide wires, arbitrarily defined as those with a
diameter 0.024 in., and of microcatheters that have visible tips and that readily track over such
wires, even through very tortuous vascularity, has facilitated substantial advances in both
diagnostic and interventional angiography.
Although methods of vascular access have evolved to some extent since Seldinger developed
the removable core needle to allow insertion of a guide wire, there have been relatively few
major advances. There is currently wide use of micro-puncture devices, which consist of a small
needle that is usually used with a stiff 0.018-in. guide wire with a floppy, steerable tip and a
two-part sheath (an inner 3 Fr and an outer 4 or 5 Fr), so that vascular access is gained with a
small, presumably less traumatic needle and then this access is safely dilated to a size
sufficient for either high-volume contrast injection (6-8 mL/second) or exchange for a larger
guide wire and catheter. One major advance in equipment has been the development of arterial
closure devices, several varieties of which are currently available (34, 35, 36, 37). True closure
devices fall into three categories, and they must be distinguished from simple devices intended
to help shorten manual compression time, such as a patch that is designed to enhance
hemostasis at the skin entry site or a modified balloon-on-a-bandage that may exert a small
amount of local pressure. The first type of closure device deploys a plug in the access tract
that is completely outside the vessel and then requires manual compression (the Vasoseal
device; Datascope, Mahwah, NJ). Second are devices, exemplified by Perclose (Abbott
Vascular Devices, Redwood City, CA), which suture the access site closed. Third are devices
that seek to sandwich, block, or grab the access site and thus occlude it. These include the
Angio-Seal device (St. Jude Medical, St Paul, MN), the Starclose (Abbott Vascular Devices),
and the Duett (Vascular Solutions, Inc, Minneapolis, MN). The Angio-Seal in essence forms a
sandwich around the access site, with a small plastic anchor in the vessel that is pulled against
the arterial access by a suture with a small collagen patch on the outside. The Starclose pulls
the vessel wall up into a sheath and then deploys a Nitinol clip around the exterior of the access
site. The Duett device infiltrates a mixture of thrombin and collagen just outside the access site
while the hole itself is kept occluded by a balloon in the vessel. Multiple additional closure
devices are either available or under development, and all add cost to the procedure, with an
acquisition cost of $250 to $300. The trade-off is that when such devices are successfully
deployed, they save the operator compression time and allow for much more rapid ambulation
of patients (1-2 hours), a substantial convenience for all concerned. They are also clearly more
comfortable for patients. Further, these devices can be used while patients are still fully
anticoagulated, significantly shortening the time to discharge. Whether or not the added cost is
justified is a question that is difficult to answer conclusively. It is clear, however, that these
devices are generally effective and safe, save time, and tend to make the overall experience of
the procedure better.
There are a few important principles regarding the use of catheters and guide wires that are
worth reiterating. As a general rule, the smallest possible catheter that will achieve the desired
objective should be utilized. All catheters have limited
injection rates. In general, a single-endhole catheter should not be utilized for injection rates >8
mL/second, since higher rates will cause the tip to move and potentially cause damage to the
vessel wall. For rates higher than this, a multisidehole catheter (e.g., a pigtail or tennis racket)
should be used. The packages for all commercially available, U.S. Food and Drug
Administration (FDA)-approved catheters indicate the maximum pounds per square inch that
can be used. It is almost impossible to generate sufficient pounds per square inch by hand to
cause the rupture of a catheter. In fact, even utilizing pressure injectors with pressures set at
the usual maximum, 1,000 PSI, rupture of the catheter itself will almost never occur. If rupture
does occur, it will most often be at the weakest points in the system, the connections, such as
the injector tubing to the catheter hub or the catheter hub to the catheter itself. If a stopcock or
a flow switch is interposed, as it often is for convenience, only one that is clearly marked high
pressure should be used with injection rates >8 mL/second. While rupture of a connection is
inconvenient, it is essentially never a danger to the patient. The only additional considerations
are that it is sometimes useful to allow the injection rate, and thus the pressure, to rise over a
second or more, to prevent movement of a tenuously placed catheter or to prevent damage to
a small vessel with subselective catheter placement.
In general, it is desirable to keep both the catheter and the guide wire in the bloodstream for as
brief a period as possible. All catheters should be flushed before initial use and then at intervals
of 2 to 3 minutes maximum, and all guide wires should be carefully wiped between catheter
exchanges and after each removal, with a moistened gauze or a Telfla pad. With catheters, it is
usual to use a single flush distal to the great vessels and a double flush more centrally, to
ensure that no air bubbles are delivered. That is, when a syringe is connected to the catheter a
small amount of blood is drawn back and this syringe is discarded. A second syringe is then
attached, a very small amount of blood is withdrawn into the syringe to ensure that any air
bubbles in the line are now in the syringe, and then the syringe is carefully injected with
heparinized saline, with the hub of the syringe down and the barrel held vertically. A similar
procedure is utilized when connecting a catheter to an injector, to ensure that regardless of
injection site, no air bubbles are in the line or are injected. The injection of microscopic air
bubbles is, in reality, probably unavoidable, as small air bubbles may be present in catheters
despite ideal flushing and attachment technique (38). Nonetheless, great care should be taken
to ensure that these are minimized, particularly in sensitive arterial beds.
An additional principle is that no single catheter is ideal for any single indication. All
angiographers develop comfort and skill with particular catheters and guide wires. It is
important, however, to limit the time spent during a case in utilizing any single catheter and wire
combination while trying to catheterize a specific vessel or organ. If a given combination does
not work after a certain period of time, a different combination should be used. While this is
very simple and obvious, it is easy for all angiographers to lose track of time during difficult
catheterization attempts. Prolonged attempts often needlessly increase radiation exposure to
both the patient and the operator, and limiting the radiation exposure should be a continual
consideration with all angiography.
ANCILLARY MEDICATIONS
Basic principles regarding medications in angiography are relatively simple. First, an adequate
history and preprocedural assessment are necessary prior to all angiograms, whether
diagnostic or interventional. This should include a listing of all medications the patient is on as
well as all medications that the patient is allergic to. Additionally, it is very important to prepare
the patients appropriately for procedures. This includes obtaining informed consent. Informed
consent is often considered a necessary evil for legal protection, but it is actually a process of
giving and receiving informationnot primarily to protect the angiographers but, rather, to
ensure that the patient understands what is to be done and becomes as comfortable as
possible with the proposed procedure. Achieving this will improve the ease and safety of the
procedure and, also, will reduce the risk of legal action should a complication occur (39). Good
sedation and good analgesia are also crucial, as is monitoring patients' vital signs (including
pulse oximetry) prior to, during, and following the procedure, until they are awake and alert.
Prior to terminating monitoring and discharging patients, they not only should be clinically stable
but also should be able to understand what was done and what limitations must be observed,
such as when walking and medications can be restarted. The American Society of
Anesthesiology (ASA)'s scale is helpful in classifying patients prior to a procedure and,, helping
to identify those who are at particular risk (Table 4-1). This scale ranges from 1 (a normal
healthy patient) to 6 (a patient who is brain-dead). In general, angiograms are performed in
patients in classes 2 to 4, that is, patients with significant medical conditions that have
significant systemic effects or are potentially life-threatening. The ASA guidelines for sedation
are also helpful (40, 41, 42).
The key medications utilized in diagnostic angiography are local anesthetics, sedatives, and
opiates. Local anesthetics play a major role, since pain is most often related to vascular
access, not to other components of most angiograms. Local anesthetics are thought to act by
altering the depolarization of the neuronal membranes by blocking the fast voltage-gated
sodium channels. If used intradermally within recommended dose limits, they very rarely cause
adverse events. For lidocaine hydrochloride (Xylocaine), which has been available since 1948,
the dose limit is 4.5 mg per kilogram without epinephrine and 7 mg per kilogram if epinephrine
is part of the formulation. The dose should not exceed 300 mg overall, or 30 mL of 1%
lidocaine. The usual duration of action of lidocaine is 30 to 90 minutes. Bupivacaine (Marcaine)
is very similar but longeracting, with a duration of action of 1.5 to 3 hours. Its maximum dose is
250 mg, or 50 mL of the usual 0.5% concentration.
Perhaps the most important function of medications is to make patients relaxed and
comfortable before the procedure starts (43). That is, it is easier to prevent pain and anxiety
than to eliminate them after onset. Midazolam (Versed) is the most frequently utilized sedative,
although other benzodiazepines including lorazepam (Ativan) and diazepam (Valium) are also
utilized. All have a sedative and amnesic effect, and
may cause respiratory depression, in a dose-dependent fashion. Both amnesia and respiratory
depression occur more frequently in older patients. Local irritation on intravenous injection may
occur with benzodiazepines; this is infrequent with midazolam, since it is hydrophilic, but
common with diazepam, which is lipophilic. The usual initial dose of midazolam is 0.25 to 2 mg
intravenously. The dose is then titrated to achieve sedation, preferably with a degree of
amnesia. Should respiratory depression occur, flumazenil (Romazicon) is a specific antagonist.
The usual dose is 0.2 mg/minute intravenously to effect, with a maximum of 3 mg per hour. The
onset of action of flumazenil is 1 to 2 minutes, with a peak effect at 6 to 10 minutes, and repeat
dosing is often necessary due to the short half-life of this antagonist.
TABLE 4-1 ASA CLASSIFICATION OF PATIENTS PRIOR TO SURGERY
1. A normal healthy patient.

2. A patient with mild systemic disease.
3. A patient with severe systemic disease.
4. A patient with severe systemic disease that is a constant threat to life.
5. A moribund patient who is not expected to survive without the operation.
6. A declared brain-dead patient whose organs are being removed for donor purposes.
Source: American Society of Anesthesiologists. ASA Relative Value Guide 2002.

Code 99140. Park Ridge, IL: ASA; 2002:xii.
Pain control in angiography is most often achieved with the use of a short-acting opiate agonist,
although pain control is generally far less important than prevention and control of anxiety. It is
important to remember that opioids are synergistic with benzodiazepines, and this interaction
increases with age. Fentanyl is the opioid agonist most often used during angiography, as it has
a short duration of action. The relative potency of common opiates for pain control is 100 to
200 mg of fentanyl = 10 mg of morphine = 75 to 100 mg of meperidine (Demerol). Opioids
have a variety of side effects, but the most often encountered is respiratory depression. If
treatment is needed, naloxone (Narcan), a pure opioid antagonist, is given, with a slow infusion
of a dilute solution. One milliliter (0.4 mg) is diluted with 9 mL of normal saline, and 1 to 2.5 mL
is given every 1 to 3 minutes, titrated to alertness without pain.
A more complete discussion of pain control is beyond the scope of this chapter. It is important,
however, to consider the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control.
Toradol (ketoralac tromethamine; Hoffman-LaRoche USA) is the only NSAID that is available for
intravenous use. For control of short-term pain, it is as effective as morphine or other opiates
and tends to have fewer side effects. The usual dose is 15 to 30 mg, intravenously,
intramuscularly, or orally. For control of postprocedural pain, 15 mg can be given every 6 hours
for a maximum of 48 to 72 hours. Like all NSAIDs, it may have an adverse effect on hepatic
function and it does have antiplatelet effects that must be considered. It is, however, a very
useful and generally safe medication for short-term pain control.
A number of additional medications are commonly used during angiography. These include
various anti-emetics. For prophylactic purposes, selective 5-HT-3 receptor antagonists, such as
Ondansetron (Zofran; GlaxoSmithKline) and Granisetron (Kytril; Roche Laboratories) are very
effective. This class of drugs is very expensive and is less effective if given once nausea and
vomiting have occurred. They can be given orally or intravenously. Once nausea and vomiting
occur, no single drug is always effective, and so it is important to be aware of the various
choices. Compazine (prochlorperazine) is a phenothiazine derivative. It can be given at a dose
of 2.5 to 10 mg intravenously, intramuscularly, orally, or rectally. Other commonly used and
often effective medications are hydroxyzine (Atarax, Vistaril), given orally or intramuscularly at a
dose of 25 to 100 mg, or promethazine (Phenergan), given at a dose of 12.5 to 25 mg orally or
rectally.
Another drug class that is important in angiography patients is anticoagulants, most often
heparin and its derivatives. Heparin is a large molecule with many distinct functions and sites of
action, including anticoagulation at a number of different sites in the coagulation cascade,
antiplatelet effects, and antiproliferative effects. It acts primarily as a cofactor for anti-thrombin
III. Low molecular weight heparin derivatives, in general, do not have the anti-thrombin III effect
but, rather, act at points more proximal in the coagulation cascade, for example, anti-Factor Xa
(44,45). Heparin-induced thrombocytopenia, a true allergic reaction to heparin, is relatively
common with unfractionated heparin, occurring in as many as 10% of patients, but is far less
frequent with low molecular weight heparins (46,47). These newer drugs are, consequently,
generally safer, with a lower incidence of bleeding, but in most instances are equally effective.
Compared to heparin, they tend to have longer half-lives, of the order of 12 hours, compared to
roughly 90 minutes. Unlike heparin, their effect cannot be measured with the activated partial
thromboplastin time, since their action is not thrombin inactivation. It is usually not necessary to
obtain specific studies for bleeding risk on patients receiving low molecular weight heparin but,
rather, to ensure that these medications have not been administered for at least 12 hours prior
to an angiogram or other invasive procedure.
Aspirin and now clopidogrel (Plavix; Sanofii-Aventuis, Nutley, NJ) are very widely used,
particularly in patients with prior coronary interventions, for their substantial antiplatelet effects.
Nonetheless, it is not usually necessary to stop either of these before angiography, and in many
patients, the risk of stopping is probably greater than the minimal increase in bleeding risk with
which they are associated (48,49). In fact, it is usually considered imperative to have patients
on both aspirin and clopidogrel before major percutaneous coronary or carotid interventions.
Another medication that is important for radiologists to be aware of is Metformin (50). This
medication is widely utilized for control of type II diabetes mellitus and is marketed in various
forms, including Glucophage and Glucovance. It acts by decreasing peripheral glucose uptake
and utilization and is eliminated unchanged in the urine. The major concern with Metformin is the
development of lactic acidosis, fatal in up to 50% of patients, that occurs due to delayed
elimination, secondary to poor renal function, particularly when there is poor renal perfusion
(i.e., congestive heart failure [CHF]) or poor hepatic function and impaired hepatic glucose
metabolism (50,51). The theoretical worry is that contrast agents will decrease renal function,
increase the half-life of Metformin, and predispose to lactic acidosis. The real concern,
however, is underlying renal dysfunction. Metformin is contraindicated in patients who do not
have normal renal function. This should be established prior to the utilization of any contrast
agents. The current FDA-approved package insert states that Metformin should be stopped at
the time an iodinated contrast agent is administered and not restarted for 48 hours. Metformin
should be started, however, either initially or after contrast administration, only if there is no
indication that there is renal dysfunction. This does not necessarily indicate that serum
creatinine is required either in every patient prior to contrast administration or in all patients on
metformin after contrast has been given. The most important factor is that angiographers
should review the renal status of all patients, and if there is any indication of renal dysfunction
(elevated serum creatinine, decreased estimated glomerular filtration rate [eGFR]), the patient
should not have been on metformin, and it should not be restarted.
CONTRAST AGENTS
The history, physiology, and clinical role of iodinated contrast agents are extensive and
complex. Contrast agents were first utilized within a year of the first description of x-rays by
Roentgen (52). Without contrast agents, x-ray angiography would be impossible. Iodine has
long been utilized in contrast agents to provide the necessary opacity, initially as sodium iodide.
This, however, was painful and toxic. This toxicity was markedly decreased when the iodine
was linked to a four-carbon ring, and development of such a compound, after much trial and
error, led to the first successful intravenous urogram in humans (53,54). In the 1950s, a fully
substituted six-carbon ring was
first utilized (55). This remains the basic formulation for all currently available iodinated contrast
agents. To that point, contrast agents had evolved primarily to improve safety, although pain
and generalized discomfort remained a major concern. It became obvious that the major factor
related to pain on injection, and a major concern regarding overall safety of these contrast
agents, was osmolality, a function of the number of particles in solution. As the iodine
concentration increases, therefore, the osmolality increases. That is, a contrast agent with a
concentration of 370 mg of iodine/mL has a substantially higher osmolality in solution than one
with 250 or 300 mg of iodine/mL. The original fully substituted benzene ring dissociated in
solution into a cation and anion. The anion consisted of the negatively charged benzene ring
with the three attached iodine atoms. The remainder of the molecule provided increased safety
and stability. The cation was present to stabilize the molecule during production, but dissociated
in solution, thus increasing the osmolality by a factor of two, but with no contribution to the utility
of the molecule. These widely used and generally extremely safe compounds have an
osmolality in the range of 1,200 to 2,000 mOsm/kg, while the osmolality of blood is 280 to 300
mOsm/kg (Fig. 4-6). Torsten Almen, a then-young Swedish radiologist, reasoned that these
ionic monomers would be far less painful, specifically on intraarterial injection, if they had a
lower osmolality. He accomplished this in 1969, with the development of a compound called
metrizamide (56). Instead of a cation that dissociated in solution, the benzene ring contained a
stable side chain, and this substitution decreased the osmolality by half. Pain was markedly
decreased with metrizamide, as were other minor complications, such as a feeling of warmth,
nausea, and vomiting. Metrizamide, however, was not stable in solution and was found to have
some unexpected central nervous system side effects. With changes in the side chains on the
benzene ring, this nonionic, nondissociating formulation is what is utilized essentially universally
today (57).
These nonionic formulations, however, remain hypertonic to blood, with an osmolality in the
range of 550 to 700 mOsm/kg. If two nondissociating benzene rings are linked, each with three
iodine atoms attached, the resulting dimer has half the osmolality at an equal iodine
concentration and is, therefore, in theory, isotonic to blood. In general, however, these
formulations have a viscosity that is twice that of the nonionic monomers. Two such contrast
agents have undergone extensive clinical investigation and use, and a third is under
development. Only one, iodixanol (Visipaque; GE Healthcare, Princeton, NJ), is currently widely
available for intravascular use (58). It is available at iodine concentrations of 280 to 320 mg/mL,
with additives to make it isotonic to blood.
FIGURE 4-6. Characteristics of major categories of iodinated contrast media.
Contrast agents are probably the safest of all medications, in terms of the incidence and
severity of complications versus the frequency and volume of their use. Nonetheless, adverse
events do occur. Some are predictable, such as contrast-induced nephropathy (CIN), and
some, such as rare anaphylactoid reactions, are not. It is important to be aware of the types of
reactions that can occur, their risk factors (insofar as they are known), effective prophylaxis,
and necessary treatment.
Much of the literature regarding adverse events associated with contrast agents is difficult to
interpret, for several reasons. First, many of the severe adverse events that occur in
association with the administration of contrast agents may not in fact be caused by the contrast
agents themselves. That is, bad things happen to sick people. It has been shown in several
studies that events that may be ascribed to one cause (e.g., contrast agents or the
angiography procedure itself) may actually occur with equal frequency in the absence of this
inciting agent. In fact, if deaths associated with contrast agents are examined, very few are
actually due to the contrast itself: most are related to underlying processes, such as advanced
cancer, severe cardiac disease, or trauma (59). Second, many of the adverse events reported
are somewhat subjective. Examples of this are nausea, dizziness, and shortness of breath.
While nausea is invariably classified as a minor adverse event, shortness of breath may be
interpreted as indicative of anxiety, bronchospasm, or laryngospasm and considered potentially
life-threatening. Since all three can occur, if patients are not evaluated carefully, the wrong
attribution may be made. Similarly, although severe anaphylactoid reactions clearly occur after
the administration of contrast agents, significant vasovagal reactions are far more frequent. A
vagal response is characterized by hypotension and bradycardia, may lead to loss of
consciousness, and might then be interpreted as an anaphylactoid reaction. It is well known
that anxiety may lead to excessive, unopposed vagal activity and, then, hypotension and
bradycardia; the contrast agent or the start of the angiogram may precipitate such a response
but is not usually the prime etiologic factor. Finally, there is no uniform categorization of adverse
events. In different studies, similar events are characterized differently by different observers
(nurse, technologist, or physician) and the significance ascribed to that reaction is a function of
the experience, education, and bias of the observer. A vasovagal reaction that is not
appropriately recognized may be considered life-threatening by one
observer but then may be recognized, appropriately treated, and classified as an adverse event
of moderate severity, unrelated to the contrast agent, by another. Similarly, shortness of
breath, even in the absence of wheezing, may be classified as an anxiety reaction by one
observer and as an exacerbation of asthma by another.
Minor adverse events occur in up to 5% of patients who receive nonionic iodinated contrast
agents (59,60). They include discomfort on injection, nausea, minor vomiting, and even urticaria.
The vast majority of these are mild, require no treatment, and do not increase the risk of a
future adverse event. If any of these adverse events persist or worsen, therapy can be
instituted but progression to more severe reactions is exceedingly rare. Administration of
diphenhydramine maleate (Benadryl) is effective for relief of pruritus associated with urticaria,
but due to its minor sedative effect, patients should be strongly cautioned against driving or
operating heavy equipment for at least 4 hours after its administration.
Bronchospasm after the administration of contrast is not rare. It occurs almost exclusively,
however, in patients who have underlying asthma, particularly if the asthma is active. It is best
treated with the use of -agonist inhalers, and most at-risk patients have such inhalers with
them. Bronchospasm is characterized by end-inspiratory wheezes, either audible or on
auscultation. Laryngospasm is potentially more important. It occurs far less frequently, is not
usually associated with asthma, and is diagnosed by the presence of expiratory wheezes. It
may be associated with angioneurotic edema and should be observed carefully. If
laryngospasm is symptomatic, with shortness of breath with hypoxia, or if bronchospasm does
not respond to an inhaler, oxygen should be administered via a non-rebreather mask, and
epinephrine should be given either intramuscularly, subcutaneously, or intravenously. For
laryngospasm, the usual dose is 1 mL of epinephrine at a concentration of 1:10,000
intravenously. Epinephrine can also be administered at a concentration of 1:1,000
subcutaneously at a volume of 0.1 mL. It is probably safer, however, to remember and use only
one concentration of this very potent medication, and that is the 1:10,000 preparation that can
be administered either subcutaneously or intravenously (1 mL of the 1:10,000 preparation
provides an equivalent dose to 0.1 mL of the 1:1,000 preparation).
Rarely, a variety of cardiac and central nervous signs and symptoms may occur after the
administration of contrast agents. All require appropriate treatment. For any adverse events
that occur, the universal approach should be to follow the BLS and ACLS algorithms (A =
airway/assessment, B = breathing, C = circulation; institute ACLS and call a code).
Full-blown anaphylactoid reactions occur very rarely following administration of contrast agents,
but there is essentially no way to predict when they will occur. It is clear that these reactions
are not allergies in any classic sense. If a patient who experienced a contrast reaction truly had
an allergy, then with readministration the same or a more severe reaction would occur. This
does not occur with contrast agents (59, 60, 61, 62, 63). Overall, although a prior reaction is
the single best predictor for a contrast reaction, recurrent reactions occur in only 7% to 25% of
patients who have a history of a reaction. Even though contrast reactions most often present
like allergies, no convincing evidence of contrast agents acting as specific antigens has ever
emerged. Some of the concern and confusion regarding the life-threatening reactions occurs
because they clearly mimic classic anaphylaxis. Regardless of the pathophysiology, the
treatment consists of the appropriate BLS and ACLS algorithms. Epinephrine should be
administered as needed and a full code should be called. Always be aware, however, that
epinephrine may cause hypertension and tachycardia, and this may be dangerous in patients
with underlying cardiac disease; it should be used only when absolutely necessary. On the
other hand, medications that are sometimes considered for treatment of acute, severe
anaphylactoid reactions, such as Benadryl and corticosteroids, are totally inappropriate. While
Benadryl is an effective H1 and H2 antagonist, if administered 12 hours prior to the inciting
event, it is not effective once a major anaphylaxis-like reaction has begun. Similarly,
corticosteroids are effective at stabilizing cellular basement membrane and have many uses,
but they are not effective for a minimum of several hours after administration and, therefore,
have no role in the treatment of serious acute reactions.
The concept of prevention of reactions is an extremely important one. Previously stated caveats
are worth repeating: First, it is impossible to accurately predict who will have a reaction
following contrast agent administration, and therefore it is essential that whenever and
wherever contrast agents are given, the equipment and expertise to treat a severe, life-
threatening adverse reaction are readily available. Second, a prior reaction is the single best
predictor of a recurrent reaction. Even though most recurrent reactions are mild and no more
severe than the initial ones, and the likelihood of a recurrent reaction is >25%, it is important to
be aware of whatever prior reactions might have occurred, since severe, life-threatening
reactions can, rarely, recur.
The prophylactic administration of corticosteroids to prevent recurrent contrast reactions is
widely considered useful and even, by some, imperative. It is important, however, to be aware
of the data regarding their efficacy. First, the best available study (64) showed that if 32 mg of
methylprednisolone was administered 12 and 2 hours prior to contrast administration, but not if
it was administered as a single dose 2 hours prior to administration, there was a decreased
incidence of adverse reactions. This was a high-quality prospective randomized trial, but it did
not include the major at-risk population: only patients who had not had a prior contrast reaction
were included. Further, life-threatening reactions occur infrequently, with an incidence of
<1:5,000. This study of about 6,800 patients, then, was insufficiently powered to determine
whether or not corticosteroids decrease the incidence of severe and life-threatening reactions.
Several subsequent large registries have suggested that steroid prophylaxis does prevent minor
reactions but does not prevent life-threatening reactions (59).
Another important and often not recognized category of adverse events associated with
contrast agents is delayed cutaneous reactions. While acute cutaneous reactions such as
urticaria are well known, many radiologists are not aware that such delayed rashes even occur.
In fact, they occur in up to 10% of patients, with an onset between 12 hours and 7 days after
the administration of contrast (65, 66, 67). Because of this delayed onset, they are often
ascribed to other causes. Delayed cutaneous reactions present with a pruritic eruption that
often progresses from very focal to diffuse over time, and they generally respond to topical
steroids. They may, however, be severe and progress to Stevens-Johnson syndrome or even
to fatality. These reactions are thought to be mediated through a T-cell delayed hypersensitivity
mechanism and tend to recur, particularly if the same contrast agent is readministered (61).
They also appear to be more frequent following the use of a nonionic dimer versus a nonionic
monomer (66). If the reaction is extensive or symptomatic, it may be appropriate to obtain
consultation from a dermatologist and it is particularly important to clearly and prominently
document that a patient has experienced one.
CIN is a complex and incompletely understood entity. It is not important because it leads to
acute renal failure, although this may (rarely) occur. Rather, it is important because overall
morbidity and mortality are worse in patients who develop CIN than in those who do not (68,
69, 70).
The precise pathophysiology of CIN is not known. The likeliest explanation is that contrast
agents, for a variety of reasons,
cause hypoxia in the already-borderline hypoxic region of the thick ascending limb of the renal
tubules in the outer medulla. This hypoxia in turn leads to free radical formation and cell injury
and death. Although the incidence of CIN has been investigated, it is impossible to come up
with precise numbers since there are so many relevant variables. It is likely that CIN is one of
the leading causes of in-hospital acute renal failure (69). A key consideration with CIN is that it
occurs only in patients who do not have normal renal function. It must be kept in mind, however,
that such renal dysfunction is not always reflected in an elevated serum creatinine (71). Serum
creatinine is a good reflection of GFR, but an inexact one, since creatinine production
decreases with age and decreasing muscle mass, and is lower in women than in men. Also,
GFR normally decreases with age. A normal serum creatinine level in an elderly, small female,
then, may actually equate with a marked decrease in true GFR. On the other hand, a normal
serum creatinine in a healthy young patient indicates a normal GFR. To improve the accuracy of
risk assessment, one of the two widely available formulas should be used to determine the
estimated GFR (72, 73, 74). Fortunately, many clinical laboratories currently report an
estimated GFR whenever serum creatinine is requested.
If renal function is decreased, other risk factors become important. These include diabetes
mellitus (75,76), advancing age (perhaps in part because of the concomitant decrease in GFR),
and factors that decrease renal perfusion, such as CHF and major surgery. Concurrent use of
other nephrotoxic medications (aminoglycosides, certain chemotherapeutic agents, possibly -
blockers or high-dose NSAIDs) is also important. Dehydration is also a major concern, and is a
focus for prevention of CIN in all patients.
It is probably not necessary to measure serum creatinine in all patients undergoing
angiography; criteria for obtaining one are relatively clear. A recent serum creatinine (within 1
month in stable patients but within 1 to 2 days in patient with changing clinical status or with
acute risks) is indicated in those with any history that would suggest the possibility of renal
dysfunction. This includes recurrent urinary tract stones, bladder outlet obstruction, diabetes
mellitus, concurrent nephrotoxic medications, significant CHF, marked dehydration, and recent
surgery. Until the last decade, the only effective response to the presence of significant renal
dysfunction and additional risk factors was either to avoid administration or to severely limit the
volume given. Now, however, a great deal has been learned and there are several promising
prophylactic approaches to decrease the risk of CIN. Achieving normal intravascular volume by
hydration is, by consensus, the most important prophylactic approach (77). Although there are
no studies that specifically examine hydration versus no hydration, it is possible to reach several
conclusions. Hydration is more effective with normal saline than with half-normal saline,
intravenous hydration is more effective than oral hydration (presumably in large part simply
because patients do not drink sufficient amounts), and 12 hours of hydration is superior to 4
hours. The most important practical point is that efforts should be made to ensure that all
patients are well hydrated prior to the administration of contrast, and this cannot be achieved
with casual oral hydration or with 1 to 2 hours of intravenous hydration. It is particularly
important to keep this in mind in elderly patients since they are often mildly dehydrated, and it
has been the usual practice to inadvertently encourage dehydration in patients prior to
angiography by requesting that they remain NPO for long periods (78, 79, 80, 81).
Among other prophylactic approaches, n-acetylcysteine (nAC) has been most widely
investigated, although some questions remain unanswered (82, 83, 84). The likely mechanism
of action of nAC is twofold. First, it acts as a free radical scavenger, preventing the toxic
effects of oxygen free radicals. Second, it stimulates the production of endothelial nitric oxide
synthase, a potent endogenous vasodilator that may lead to improved medullary blood flow
and, thus, improved oxygenation. nAC can be administered orally or intravenously, and the ideal
dose is still not clear. In most studies the dose of nAC is 600 mg twice a day for 2 days,
beginning on the day before contrast administration. Recent studies have suggested that twice
this dose may be more effective (83,85). Another recent study suggested that intravenous
administration of nAC begun 1 hour prior to contrast administration may also be effective in
preventing CIN (86). If confirmed, this makes the use of nAC much more convenient, for both
the patient and the radiologist. There is no major risk with the use of nAC, as it is inexpensive,
readily available, and safe. Many other prophylactic strategies have been employed for CIN,
and most either are ineffective, are awkward to employ, or have unproven benefitto-risk ratios
(87,88). These include theophylline, endothelin antagonists, prostacyclin analogues, statins, and
ascorbic acid. One study has shown that the use of sodium bicarbonate intravenously,
beginning 1 hour prior to the administration of contrast, was effective (89). The infusion protocol
was very simple: three vials (1,000 mEq) of sodium bicarbonate are dissolved in 1 liter of
normal saline or D5W and infused at a rate of 3 mL (3 mEq) per kilogram over the 1 hour prior
to contrast administration and then at 1 mL/kg (1 mEq/kg/hour) over the subsequent 5 hours.
This regimen also is likely to be safe and inexpensive, although a little awkward to employ, but
its efficacy must be compared in further studies. Two more recent studies suggest that it may
be effective in combination with nAC (90,91). One other area of interest is the specific contrast
agent. There is some evidence that the nonionic dimer leads to a lower incidence of CIN than
nonionic monomers (92). This is still controversial, as the direct comparisons are very limited,
but it is reasonable to conclude at this point that the use of this specific isotonic agent will not
have negative effects and may be helpful.
CIN, in summary, is an important and complex problem. Its natural history is that it occurs
essentially only in patients with underlying renal failure, is generally self-limited, and rarely leads
to the need for either temporary or permanent dialysis. It is clinically important because it is
associated with increased cardiovascular and all-cause morbidity and mortality, for reasons
which are not clear. Prevention rests on, first, recognizing that there is a risk, as manifest by
either an elevated serum creatinine or a diminished eGFR (even with normal serum creatinine).
Prevention, by current consensus, requires hydration and limiting the dose of contrast agent
utilized. Other strategies that appear to have a positive risk-benefit ratio, at this time, include
use of nAC orally or intravenously, probably concomitant use of sodium bicarbonate, and
perhaps use of the nonionic dimeric contrast agent.
Alternative contrast agents have been investigated in patients with renal compromise, mainly
carbon dioxide and gadolinium chelates. Carbon dioxide has the advantage of being inexpensive
with very low toxicity. However, it is a gas and is thus both compressible and invisible, and its
use requires cooperative patients (93). With experience and care, it is a good, albeit partial,
substitute for iodinated contrast agents (Fig. 4-7). Gadolinium contrast agents have also been
fairly widely investigated for use in angiography. Recently, it has become widely recognized that
there can be severe complications associated with gadolinium use, with the development of
nephrogenic systemic fibrosis, which can be fatal (94, 95, 96). Its incidence is unknown, but to
date it seems limited to patients with severe renal dysfunction. Most of the reported cases have
occurred after administration of high doses (>0.2 mmol/kg) of gadodiamide, a nonionic
formulation that is thought to have the loosest binding of the gadolinium to the chelate of any of
the currently available agents, but cases have also been reported with most of the other widely
used Gd-chelates. At this time,
it is wise to avoid the use of gadolinium in patients with severe renal compromise or, at most,
use a very low dose. Many of the reported cases have occurred in patients who underwent
either magnetic resonance angiography or catheter angiography with the use of a gadolinium
agent as a substitute for iodinated contrast agents, both settings in which doses >0.01 mmol/kg
of Gd-based contrast agents are usual (97,98). Although opinions and anxiety abound (the FDA
has issued a black box warning concerning the use of Gd-based agents in patients with renal
dysfunction (99), at this time, the most logical approach seems to be to avoid the use of
gadodiamide in patients with significant renal dysfunction and to use as low a dose as possible
of any Gd-based agent as possible in patients with significant renal dysfunction. This includes
patients on dialysis, patients immediately prior to or following renal transplant, those with
hepatorenal syndrome, and those with other compromise of renal function (e.g., eGFR <20-30
mL/minute). Although immediate dialysis has been recommended (100), this does not seem to
be either necessary or advisable as a general policy. Nephrogenic systemic fibrosis as a
clinically important entity is a rapidly evolving area of concern and information, and it is likely to
be better understood, and approaches to it better defined, within the next year.
FIGURE 4-7. A: Aortogram with CO2 in a 90 year old with elevated serum creatinine. No
proximal left renal artery stenosis and a very small single right renal artery. This image
demonstrates less contrast differentiation than those obtained with iodinated contrast
agents, but the information content is essentially identical. B: Selective right renal artery
injection with a nonionic dimeric contrast agent shows a small kidney and no reflux from the
renal artery, suggesting osteal renal artery stenosis.
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> Table of Contents > Section II - Vascular Imaging > Chapter 5 - Doppler Ultrasound in Abdominal Vascular Interventions
Chapter 5
Doppler Ultrasound in Abdominal Vascular
Interventions
Ajay K. Singh
Since its first application in 1957, Doppler imaging has become an integral part of vascular
imaging. Doppler imaging includes continuous wave, pulsed Doppler, color Doppler ultrasound
(US), and power Doppler (1, 2, 3, 4, 5). Continuous wave Doppler is used most often as
portable bedside imaging and in the operating room to assess vascular patency of larger
vessels.
While continuous wave Doppler lacks depth resolution and suffers from aliasing, pulsed Doppler
allows depth resolution and is only occasionally hindered by aliasing. The time interval between
transmission and return of a US pulse is used to calculate the distance from which the Doppler
shift was generated. The color assignment in color Doppler imaging indicates the mean pixel
speed and direction (vector) of the moving blood. Power Doppler imaging is highly flow
sensitive but does not give speed or directional information.
Although the ideal Doppler interrogation angle is 0 degrees, this is not usually achievable, and
therefore, it should be <60 degrees for accurate velocity measurement. Pulsed Doppler
imaging is used to measure the maximum frequency shift, fD, since this cannot be done with
color Doppler:
fD = 2 fv(cos)/c
where
fD = Doppler shift
f = frequency of transmitted US
v = blood velocity
= Doppler angle
c = speed of sound in tissue being examined
If the angle between the ultrasound beam and blood flow is 90 degrees, there is no Doppler
signal detected. In reality, some signal is still detected because of blood turbulence, divergence
of beam, and fluctuation in the US beam reflection. Unlike color Doppler, power Doppler is
relatively insensitive to the angle between the US beam and the direction of blood flow.
Arterial and central venous flow is pulsatile, while portal vein flow is not (Table 5-1, Fig. 5-1A-
C). High-resistance arterial waveforms show a sharp systolic upswing, a sharp systolic
downswing, and little or no diastolic flow. Low-resistance arterial waveforms show significant
end-diastolic flow. Low-resistance waveforms are seen in renal, hepatic, and internal carotid
arteries. Arterovenous shunts show low-resistance, high-velocity arterial flow with a large end-
diastolic flow component. The draining vein in an arteriovenous shunt shows pulsatile and high-
velocity flow (Fig. 5-2).
Arterial stenosis is suggested by spectral broadening, which indicates that the range of
velocities is much wider than usual. The most severe spectral broadening is indicated by the
presence of forward as well as backward flow. The other indicators of stenosis are a
parvus/tardus waveform, an elevated resistive index, and elevated peak systolic velocities.
KIDNEY
Doppler US is the preferred imaging modality for the evaluation of renal transplants because of
its easy availability and avoidance of intravenous contrast and ionizing radiation. Doppler
waveforms are obtained from the interlobar or arcuate artery in the upper, middle, and lower
poles of the transplant kidney. The resistive index measurement is most consistent in the
interlobar-arcuate arteries (6). The resistive index equals the peak systolic velocity minus the
end-diastolic velocity divided by the peak systolic velocity. It is an indicator of renal arterial
resistance and is normally <0.7 (7).
Although a resistive index >0.7 is abnormal in a transplant kidney, this is a nonspecific finding
indicating poor diastolic flow. It can be increased in patients with transplant rejection, acute
tubular necrosis (ATN), obstruction, cyclosporine toxicity, or compression of the transplant
kidney. Reversed diastolic flow is an ominous finding and can be seen with severe ATN,
transplant rejection, and renal vein thrombosis.
In transplant patients it is important to assess the patency of the renal artery and renal vein.
The main renal artery should be evaluated for stenosis and thrombosis. Renal artery stenosis is
suggested by an elevated peak systolic velocity of >1.8 m/s. Renal vein thrombosis is
suggested by reversal of diastolic flow.
In assessing native renal arteries, the Doppler waveform shows a rapid systolic upstroke and
slower but persistent diastolic flow. The right renal vein, being shorter than the left renal vein, is
more likely to show changes secondary to cardiac and respiratory activity.
Because the accuracy of duplex US for native renal artery stenosis is variable, it is not widely
used for screening in unselected patients. The potential problems in US assessment of renal
artery stenosis include the presence of multiple renal arteries, difficulty in visualizing the main
renal artery, and operator dependence. Renal artery stenosis shows an elevated peak systolic
velocity, a delayed systolic upstroke, and a delayed acceleration time (>0.08 s) (Table 5-2,
Figs. 5-3 and 5-4). A ratio of peak systolic velocities >3.5, in the renal artery distal to the
stenosis and the aorta at the level of the renal artery, suggests renal artery stenosis (8, 9, 10).
AORTA AND INFERIOR VENA CAVA

As the aorta is a deep, lower-frequency transducers and longer pulse repetition intervals are
used for sonography. The aorta can be visualized with a 5-MHz-frequency transducer through
the left lobe of the liver. The patient should be fasting for better visualization of the aorta. The
caliber of the aorta is measured from the outer aspect of the vessel wall during
systole. The anteroposterior diameter is the most reproducible and it is used for comparing
serial studies.
TABLE 5-1 SPECTRAL DOPPLER TRACINGS
Portal vein Uniform flow with some phasicity and periodicity
Hepatic artery Low-resistance flow
Hepatic vein Triphasic waveform
Renal artery Low-resistance flow
An aneurysmal aorta by definition measures >3 cm in diameter, or more than 1.5 times the
diameter of the normal adjacent aorta (Fig. 5-5). The Doppler waveform in the proximal aorta
shows forward flow during diastole. The flow is absent or reversed during diastole in the distal
aorta. US is often used to assess the temporal growth of the aortic aneurysm. Although
computed tomography (CT) is more sensitive for the assessment of suspected aortic rupture in
the emergency setting, the demonstration of a normal aortic caliber by US makes the possibility
of aortic rupture very unlikely.
US also allows assessment of aortic dissection by demonstrating the dissection flap. Most
dissections in the abdominal aorta are an extension of a thoracic aortic dissection. The aorta
should be assessed from multiple angles to visualize the flap. The true and false lumens can be
identified by the difference in blood flow velocities on color Doppler assessment. The patency
of major aortic branches can also be assessed by Doppler sonography.
FIGURE 5-1. Hepatic vascular spectral Doppler waveforms. A: Normal portal venous flow
with normal continuous waveform and mild velocity variations due to respiration. B: Normal
Doppler waveform in the hepatic artery, indicated by rapid systolic upstroke with
continuous low-velocity diastolic flow. C: Normal hepatic vein triphasic pattern waveform
secondary to back pressure down the inferior vena cava from the heart. Pulsatility in the
left hepatic vein is greater than in the middle hepatic vein, which is greater than in the right
hepatic vein. (See the color insert.)
Sonography can be used for the assessment of subacute or chronic mesenteric ischemia but
acute mesenteric ischemia is most commonly assessed with contrast-enhanced CT. The
demonstration of hemodynamically significant stenoses in at least two of the three splanchnic
arteries, with concordant symptoms, makes a strong case for mesenteric ischemia. The
presence of extensive collaterals may mask symptoms. A peak systolic velocity of >2.8 m/s in
the superior mesenteric or celiac artery suggests the presence of a stenosis (11). A limitation
of US in evaluation of the splanchnic circulation is that disease may be demonstrated in a
significant proportion of asymptomatic patients.
The inferior vena cava (IVC) is assessed through acoustic windows similar to those used for
the aorta. Adequately hydrating and raising the patient's legs can improve visualization of the
IVC. Blood flow in the IVC is affected by respiration as well as cardiac motion. US can be used
to assess IVC diameter, patency, and thrombus extension from pelvic or lower extremity veins.
TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT

EVALUATION
The normal portal vein is located posterior to the hepatic artery. In patients with portal vein
thrombosis, a collateral vein may
be mistaken for the portal vein. In these patients the position of the collateral vein in relation to
the hepatic artery can aid in the correct diagnosis.
FIGURE 5-2. Aortocaval fistula. A: Spectral Doppler waveform in the inferior vena cava
(IVC) shows a combination of the triphasic waveform and the pulsatile arterial waveform
(arrowheads). B: Contrast-enhanced CT shows a small-caliber aorta (arrow) and an early
enhancing dilated IVC. C: Contrast-enhanced CT shows markedly attenuated common
femoral arteries because of the preferential flow of arterial blood through the arteriovenous
communication into the low-pressure central vein.
As with any other surgically placed shunt, the transjugular intrahepatic portosystemic shunt
(TIPS) also suffers from the disadvantage of neointimal hyperplasia, leading to stenosis and,
finally, occlusion. Doppler US assessment should be performed preprocedurally to confirm
patency of the portal and hepatic venous systems. Preprocedural US also assesses collateral
circulation and baseline flow speed and direction in the portal system. The portal vein velocity is
documented and this is expected to increase on post-TIPS sonography. US assessment of
TIPS should also be performed within 24 hours after the procedure to document shunt patency
and establish baseline flow directions and speed. As clinical monitoring of TIPS is not reliable,
US follow-up should be obtained before discharge from the hospital and thereafter at 3- to 6-
month intervals. The early detection of a stenosis that can be effectively treated by balloon
angioplasty will prevent later total occlusion. Often higher-frequency probes are required for
imaging of TIPS because of increased liver echogenicity, attenuation by a cirrhotic liver, and the
deep location of the shunt.
TABLE 5-2 DOPPLER CHANGES IN RENAL ARTERY STENOSIS
Increase in peak systolic velocity (>1.8 m/s)
Poststenotic spectral broadening from turbulence
Elevated peak systolic renal artery-to-peak systolic aortic velocity ratio (>3.5)
Tardus/parvus waveform
Increased acceleration index (>3 m/s2)
Increased acceleration time (>0.08 ms)
Reduced resistive index (<0.5)
The TIPS is usually placed between the right portal vein branch and the right hepatic vein.
Primary shunt patency rates of 45.4% and 26% at 1 and 2 years, respectively, have been
reported. An overall secondary assisted patency rate of 72.2% has been reported (12). The
stent is seen as two parallel echogenic lines with flared ends (Fig. 5-6). The blood flow is
usually turbulent and the velocities in the shunt are high, ranging from 50 to 270 cm per second
(13,14) (Figs. 5-7 and 5-8). The main portal vein velocities are lower, at <50 cm per second
and the blood flow is centripetal. The flow is centrifugal in the right and left branches of the
portal vein. In general, the velocities increase from the portal venous end to the hepatic venous
end of the shunt. Although blood flow through the TIPS is often nonpulsatile, pulsatility can be
seen in widely patent shunts due to transmission of right atrial pressure changes. The color
Doppler flow in the TIPS is turbulent, especially in the presence of multiple stents and stenoses.
Postprocedure hepatic artery velocities increase after TIPS placement because of the creation
of a low-resistance bypass of the hepatic circulation.
There are multiple studies in the literature with different results regarding the criteria to be used
for diagnosing TIPS stenosis, which can be due to neointimal hyperplasia or hepatic vein
stenosis. A decrease in the shunt velocity to <50 cm per second has been reported in the
presence of TIPS stenosis. A number of other criteria can be used to assess TIPS for
occlusion or stenosis (Table 5-3). Absence of blood flow on color Doppler imaging strongly
indicates thrombosis of the shunt.
FIGURE 5-3. Renal artery stenosis. A: Color Doppler image shows aliasing in the right
renal artery (arrowhead) arising from the abdominal aorta (arrow). B: Spectral Doppler
image shows an elevated peak systolic velocity (326 cm per second) in the right renal
artery. (See the color insert.)
FIGURE 5-4. Pulsus parvus et tardus in renal artery stenosis. Spectral Doppler waveform
shows delayed systolic upstroke secondary to hemodynamically significant stenosis. (See
the color insert.)
FIGURE 5-5. Abdominal aortic aneurysm. A: Sagittal ultrasound (US) shows a large
aneurysm with intraluminal thrombus, measuring 6-6 cm in the anteroposterior dimension.
B: Axial color Doppler US again demonstrates a circumferential thrombus within the
infrarenal abdominal aortic aneurysm. (See the color insert.)
FIGURE 5-6. Normal transjugular intrahepatic portosystemic shunt (TIPS) anatomy.
Ultrasound shows two parallel echogenic lines from the TIPS (arrowhead) in the liver.
FIGURE 5-7. Transjugular intrahepatic portosystemic shunt (TIPS) stenosis. A: Spectral

Doppler waveform shows an elevated systolic velocity of 264 cm/s in the portal vein
(arrowhead), suggesting stenosis. B: Color Doppler ultrasound shows reversal of blood
flow in the mail portal vein (arrowhead), suggesting TIPS stenosis. (See the color insert.)
FIGURE 5-8. Transjugular intrahepatic portosystemic shunt (TIPS) stenosis. A: Spectral
Doppler waveform shows elevated blood flow velocities of up to 266 cm per second at the
junction of the shunt with the hepatic vein. (See the color insert.) B: Fluoroscopy spot
image demonstrates stenosis indicated by waisting (arrowhead) of the angioplasty balloon
at the junction of the TIPS with the right hepatic vein.(see color image)
TABLE 5-3 DOPPLER CRITERIA FOR COMPROMISED TRANSJUGULAR

INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS) AND/OR HEPATIC VEIN
LUMEN
Absence of flow (due to thrombosis)
Shunt velocity of <50 or >190 cm/s
Hepatofugal flow in main portal vein or blood flow velocity of <30 cm/s
Increase or decrease in shunt velocity of >50 cm/s compared with velocity in initial
study
Focal area of increased velocity in TIPS or hepatic vein

Hepatopetal flow in portal vein branches
Reversed flow in hepatic vein draining stent (due to hepatic vein stenosis)
FIGURE 5-9. Acute portal vein thrombosis. A: Color Doppler image demonstrates lack of
flow in the main portal vein. (See the color insert.) B: Contrast-enhanced CT shows
intraluminal clot (curved arrow), outlined on the left by opacified blood at the confluence of
the splenic vein and superior mesenteric vein. C: Gadolinium-enhanced magnetic
resonance venography demonstrates the hypointense thrombus (curved arrow) in the main
portal vein cranial to the superior mesenteric vein confluence with the splenic vein.(see
color image)
LIVER TRANSPLANT
Doppler sonography can be used to assess preoperative vascular patency, identification of
collaterals, and malignancy prior to liver transplantation. Although not useful for acute rejection,
Doppler sonography plays an important role in the monitoring of vascular patency following liver
transplantation. In addition to the demonstration of hepatic vein, hepatic artery, portal vein and
IVC patency, US can be used to evaluate collections, hematomas, and biliary dilatation.
The findings of hepatic artery stenosis include a tardus/parvus waveform, systolic hepatic
artery velocity of >2 m/s and prolonged acceleration time. Lack of flow in the hepatic artery
adjacent to the main portal vein indicates hepatic artery thrombosis. The immediate post-liver
transplant hepatic artery waveform often shows high-resistance flow, which resolves
progressively over a few days.
Portal vein complications after liver transplantation are relatively uncommon and include
stenosis and thrombosis (Figs. 5-9 and 5-10). Portal vein waveforms can be nonphasic,
pulsatile, or turbulent after living-related liver transplantation. Although pulsatile portal vein flow
can be due to arterioportal shunting, it can often be seen in patients who have received small
grafts and may disappear without any treatment (15). A stenosis in the portal vein is quantified
by a velocity gradient increase across the visualized narrowing.
FIGURE 5-10. Portal vein thrombosis in a 53-year-old male with liver transplant. Color
Doppler ultrasound shows lack of blood flow (arrowhead in the portal vein Gortex graft.
(See the color insert.)
FIGURE 5-11. Pseudoaneurysm of the common femoral artery. A: Color Doppler
ultrasound shows blood (US) in the pseudoaneurysm (straight arrow), arising from the
common femoral artery (curved arrow). The narrow neck (arrowhead) of the
pseudoaneurysm made it an ideal case for US-guided thrombin injection. B: Spectral
tracing from the neck (arrow) of the pseudoaneurysm shows the classic appearance of
forward systolic and backward diastolic flow. C: Postprocedural color Doppler US, after
injection of 300 U of thrombin, shows complete thrombosis of the pseudoaneurysm
(arrow), indicated by lack of color Doppler flow. (See the color insert.)
FIGURE 5-12. Pseudoaneurysm of the common femoral artery. A: Color Doppler
ultrasound (US) shows blood in the pseudoaneurysm (straight arrows), arising from the
common femoral artery (curved arrow). Note the classic ying-yang pattern. (See the
color insert.) B: Postprocedural color Doppler US, after injection of 50 U of thrombin,
shows complete thrombosis of the pseudoaneurysm (curved arrow), indicated by the
echoes.(see color image)
US is also able to visualize the anastomosis of the donor and recipient IVC. Stenosis of the IVC
at the anastomosis may be manifested by dampening of the hepatic vein waveform, loss of
pulsatility, and distension of the hepatic vein. A fourfold velocity gradient change across the
anastomosis at the IVC or the portal vein suggests a hemodynamically significant stenosis.
FEMORAL ARTERY PSEUDOANEURYSM

Most iatrogenic pseudoaneurysms (PSAs) of the femoral artery are secondary to arterial
catheterization and are often secondary to poor compression or excessive anticoagulation.
Color Doppler imaging often shows the classic ying-yang pattern caused by swirling of blood
in the PSA. This is caused by entry of blood in systole and exit during diastole.
The treatment options for groin PSAs include surgical repair, coil embolization, stenting of the
native vessel to isolate the neck of the PSA, US-guided compression, and US-guided thrombin
injection (Figs. 5-11 and 5-12). US-guided transcutaneous compression therapy involves
application of pressure on the neck of the PSA for 10 to 20 minutes at a time and has shown a
success rate of >90% (16). This procedure can be painful and analgesics may be required.
Other disadvantages of US-guided compression include limited success with large
(noncompressible) PSAs and patients on anticoagulants.
US-guided thrombin injection into a PSA does not require external compression and is based on
activated thrombin converting fibrinogen into fibrin and in situ thrombosis in the presence of
factor XIII and calcium. Under US guidance, a 20- to 25-G needle is positioned within the PSA
and 0.5 to 1 mL of thrombin solution (1,000 U/mL) is injected to induce thrombosis.
Percutaneous thrombin injection under US guidance can be performed with or without intra-
arterial balloon insufflation at the neck of the aneurysm. Balloon occlusion results in parent
artery stasis distally and may lead to thrombosis, but intermittent flushing with heparinized
saline through the balloon-catheter tip can prevent this. Prolonged balloon occlusion of the
artery can also cause distal ischemia. Thus, distal pulses and ankle-brachial indexes must be
assessed before and after the procedure. Percutaneous thrombin injection without balloon
occlusion reduces the procedure time and avoids a contralateral femoral arterial puncture. This
technique should not be used if the neck of the PSA is wide since it risks occluding the parent
artery with thrombus. The success rate of thrombin injection was consistently >90% in several
studies (17, 18, 19, 20, 21). A second injection may be needed for complete thrombosis of the
PSA. US-guided percutaneous thrombin injection is the treatment of choice for femoral artery
PSAs. Surgical treatment is reserved for rare selected cases.
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pseudoaneurysms: a multicenter experience. Vasc Med. 2001;6(4):241-244.
21. Veraldi GF, Tasselli S, Firpo M, et al. US-guided percutaneous management of femoral
artery pseudoaneurysms by thrombin injection: personal experience and review of literature.
Chir Ital. 2005;57(6):723-730.
> Table of Contents > Section II - Vascular Imaging > Chapter 6 - Computed Tomographic Angiography
Chapter 6
Computed Tomographic Angiography
Joshua L. Rosebrook
Martin J. Lipton
Frank J. Rybicki
Computed tomographic angiography (CTA) has become essential in the diagnosis of vascular
disease and now plays a major role in the planning and follow-up of many vascular
interventions. Driven not only by the tremendous clinical applications, but also by the advances
in computer processing speeds, computed tomography (CT) technical design, and software
development, this technology now provides extremely high-quality, submillimeter-resolution CTA
images of all major vessels. Postprocessing allows for near-real-time reconstruction of
multiplanar and three-dimensional (3D) images that provide an intuitive representation of
disease processes optimized for diagnosis and management. Coupled with the safety,
widespread availability, and ease of use, the outstanding diagnostic image quality of CTA
makes it a robust modality for noninvasive vascular imaging.
IMAGING TECHNOLOGY
CT technology has progressed rapidly in the last decade. Advances include the development of
multiple-row detector technologies (called multidetector CT, or MDCT), faster gantry rotation
times, x-ray source modulation, and the use of multiple x-ray sources. This technology allows
for the breath hold acquisition of an isotropic volumetric data set of entire body segments in just
a few seconds. For vascular imaging, this means the ability to acquire optimized arterial phase
images without venous contamination, acquire multiple phases over large volumes for both
arterial and venous phase imaging, or acquire multiple phases of the same volume for
applications of perfusion imaging. Understanding the basics of these new technologies provides
the foundation for the performance of prudent, safe, and high-quality medical imaging.
Computed Tomography Fundamentals

The fundamental principle underlying CT involves a specialized x-ray source rotating about a
patient and a detection system recording the attenuated x-rays that have passed through to the
other side. These data are then reconstructed, and images are interpreted with respect to a
grayscale value or Hounsfield unit (HU), with water representing zero. Structures with a higher
attenuation appear brighter than water and have >0 HU (1).
Slip-ring technology was a major advance in CT because it allows for the free rotation of the x-
ray source about the patient while maintaining contact with its electronics and power sources.
Helical (or spiral) CT allows continuous movement of the patient through the rotating x-ray
source, thus creating a virtual spiral path of the x-ray beam. With helical CT, the volume of
coverage is determined by the table speed or distance traveled in the long axis (z-axis) per
gantry rotation and beam collimation. Pitch is the unitless ratio of these factors or table travel
per gantry rotation over beam collimation (2). MDCT introduced multiple detectors along the
same row, and the advances in MDCT have been significant; at present 64-slice CT scanners
are available from every major vendor.
Routine use of 64-slice scanners has greatly expanded CTA applications. Today, the dramatic
increase in both spatial and temporal resolution allows for submillimeter-isotropicresolution
imaging over entire body regions in 10 to 20 seconds. The speed of gantry rotation reduces
motion artifacts, decreased scan times, and reduces the volume of intravenous (IV) contrast
required for each study. These advantages of speed and superb anatomic detail allow for the
routine noninvasive imaging of even the most difficult of vascular territories, including the
coronary arteries.
One practical consequence of the routine use of CTA is the large number of images, a result of
the thin slices that are required for image reformatting. The problem of large data sets is
compounded when electrocardiographic (ECG) gating (detailed below) is performed, as these
exams are usually reconstructed at multiple phases of the cardiac cycle. For example, using a
state-of-the-art 64-slice CT technology in a modern emergency radiology practice, a full trauma
evaluation with multiplanar reformations (MPRs) of the spine, vasculature, and extremities can
produce up to 6,000 images. While the wealth of information obtained is impressive, the burden
on the imager can be equally dramatic. Thus, we recommend that a clear line of communication
be established between the imager and referring clinicians so that, for each individual patient,
only focused CTA exams, yielding the most specific data, are performed.
Gantry Rotation Times

Paralleling the rapid evolution of multislice technology has been the gantry rotation speed,
measured by the time it takes for the gantry to rotate 360 degrees. The gantry rotation time is
twice the temporal resolution, since the minimum number of data to reconstruct an image can
be obtained in one-half gantry rotation. All 64-slice CT platforms have gantry rotation times
<500 milliseconds, with times as low as 330 milliseconds (165-millisecond temporal resolution).
Because motion artifact reflects the average motion during the acquisition of a slice, better
temporal resolution decreases motion artifacts. Increased temporal resolution enables one to
more effectively freeze cardiac motion and allows for routine noninvasive high-quality imaging of
the coronary arteries.
Multiple Source Technologies

One approach to improving temporal resolution, other than increasing the speed at which the
gantry rotates, has been the
development of multiple x-ray sources with independent detector systems. Siemens Medical
Solutions (Forcheim, Germany) has incorporated this technology into its Definition scanner
model using two x-ray sources and two detector systems placed 90 degrees apart. The result
is that the combination of both detectors acquires 180 degrees of image data in half the time.
This improves temporal resolution from 50% of gantry rotation time to 25%, or for a gantry with
a rotation time of 330 milliseconds, image acquisition for a single slice takes only 82.5
milliseconds. In terms of cardiac imaging, this means that cardiac motion is averaged over half
the time, doubling temporal resolution. At the time of publication, testing to determine the
benefits of the improved temporal resolution in clinical practice was underway.
Electrocardiographic Gating
ECG gating synchronizes the acquisition with the electrocardiogram to minimize the effect of
cardiac motion. There are two forms of ECG gating: (i) prospective and (ii) retrospective.
Prospective gating uses the ECG tracing to plan the timing of image acquisition and is mainly
used for cardiac magnetic resonance (MR) imaging (MRI) applications. Retrospective gating
involves the simultaneous acquisition of image and ECG data so that the images can be
reconstructed after the acquisition.
CT of the ascending aorta, the aortic arch, the heart, and the coronary arteries (Fig. 6-1) uses
retrospective ECG gating. When static structural information is required, images of these
structures are acquired during diastole, when cardiac motion is usually most quiescent.
Conversely, in cardiac imaging, functional information (e.g., left ventricular wall motion
abnormalities) can be obtained by reconstructing either a specific imaging plane or a volume
throughout the cardiac cycle. The reconstructed data are then displayed as a cine loop. The
portions of the cardiac cycle that are reconstructed are called cardiac phases and are typically
named for the percentage of the cardiac cycle they represent, beginning and ending at
successive R waves (0%, 5%, 20%, etc.). The duration of each individual phase is equal to the
temporal resolution of the scanner. Phases between 55% and 75% usually provide the best
image quality because they correspond to middiastole, when the heart is most quiescent.
However, retrospective ECG gating allows for the reconstruction of any phase of the cardiac
cycle, and thus when an image in diastole demonstrates motion artifact, additional
reconstructions should be performed, as other phases will most likely yield more motion-free
images.
FIGURE 6-1. Curved multiplanar reformatted (cMPR) image from an ECG-gated coronary
CTA shows the entire extent of the right coronary artery. Using this reformation technique,
the full extent of the coronary arteries can be visualized in a single plane.
In ECG-gated CTA of the ascending aorta, aortic arch, and coronary arteries, a MDCT pitch of
<1 is required such that image data are oversampled. A typical value for the pitch is 0.2.
Because of oversampling in ECG-gated CTA, the radiation dose is higher than for CT of any
other body part. One strategy for limiting radiation exposure is current modulation, where the x-
ray tube current is varied during the cardiac cycle. The tube current is maximized during
diastole, where diagnostic images are expected, and minimized in systole, where motion is
expected to be greatest and image quality poor. Because of hardware constraints, the x-ray CT
tube cannot be instantaneously powered on and off; however, a considerable reduction (30% to
50%) in dose can be achieved using this technique. The disadvantage of current modulation is
that images of the heart during systole are of poor quality, preventing the reconstruction of
cardiac motion and, thus, preventing functional analysis.
Retrospective ECG gating also allows the operator to improve image quality through ECG
editing. This is used more commonly in coronary CTA than in ascending aorta and root imaging.
In ECG editing, the imager manually determines, beat to beat, the portion of the R-R interval
that is reconstructed. In addition, ectopic beats (e.g., a premature ventricular contraction),
which alter the R-R interval and cause significant phase reconstruction errors, can be removed.
Since the CT data are oversampled, these modifications can be made to the point where CT
data exist for adequate image reconstruction.
Radiation Exposure
CT represents an increasingly significant source of medical radiation exposure in the United
States (3,4). With x-rays gaining increasing regulatory and public scrutiny, every patient
referred for CT requires the appropriate evaluation of medical necessity versus risk prior to
radiation exposure. Understanding the basic imaging physics of CT will help ensure the prudent
use of this technology.
There are known side effects of radiation exposure. For example, skin burns and cataract
formation occur at threshold doses well beyond the dose delivered by a single CT acquisition.
However, consideration should be made for patients who are expected to have repeated CTA
through the orbits.
In CTA, the risk of a radiation-induced fatal neoplasm causes the most concern. There are no
data to confirm or refute a radiation threshold for the induction of a fatal malignancy at the
doses used for CT. Because data are so scarce, mathematical models are used to estimate
risk. These models primarily use data from the high-level exposures encountered by the
Japanese nuclear bomb survivors, extrapolating these higher nonmedical exposures to the
much lower levels of medical radiation present today (5,6). Most models do not incorporate a
threshold. However, the validity and accuracy
of both models continue to be argued in the medical literature today.
Since CT dose is discussed so frequently, and because the potential for miscommunication is
so high, the method to calculate dose is described. Three parameters describe and quantify CT
dose. The first is the CT Dose Index (CTDI), a parameter with units of milligrays (mGy) (7).
The numerical value of the CTDI is determined by measuring dose in a cylindrical phantom.
Although the phantom should somehow reflect the attenuation of a human body, the CTDI is not
used to make a statement regarding an individual patient's dose. Rather, it is used to compare
different scan protocols, to optimize scan protocols, and to compare protocols used on
different CT scanners. In contrast to parameters such as the tube current, CTDI values reflect
the delivered dose since parameters such as the scanner geometry and filtration are
considered. CTDIvol describes the dose for a single rotation (over a volume); the value is
available from the CT console of all major manufacturers.
The second parameter is the dose length product (DLP), expressed as milligrays centimeters
(8). The DLP is defined as the product of the CTDIvol and the craniocaudal extent (z-axis
length) of the scan. It characterizes the CT exposure over a complete field of view (FOV). Even
though the DLP reflects most closely the radiation dose for a specific CT examination, it is
important to keep in mind that DLP is a function of patient size (i.e., how much z-axis coverage
is required to complete the CT scan). Therefore, CTDIvol should be used to optimize exam
protocols.
While CTDIvol and DLP enable evaluation of CT scanners and comparison of protocols across
manufacturers, these values characterize only the scanner. It is the effective dose, a weighted
sum over the organ doses, that quantifies patient dose (7). The units of effective dose are
milliseverts (mSv). Since the dose to an individual organ cannot be measured directly, it is
difficult to determine the effective dose of a CT scan. However, methods have been described
to estimate effective dose from measurable values (8, 9, 10). A simple estimation is that the
effective dose is the product of the DLP and a conversion factor, EDLP, that is specific to a
body region. For example, for the chest the EDLP = 0.017 mSv mGy-1 cm-1.
As an example, consider a coronary CTA (a high-dose examination) with CTDIvol = 60 mGy. If
the craniocaudal extent of the scan is 15 cm (a normal-sized heart) the DLP = 60 mGy 15 cm
= 900 mGy cm. Since the heart is in the chest, the appropriate conversion factor is EDLP =
0.017 mSv mGy-1 cm-1, and the effective dose for this patient is 60 mGy 15 cm 0.017
mSv mGy-1 cm-1, or about 15 mSv.
Image Processing
The data demands for image acquisition and processing are greater in modern CTA than in any
other human imaging application. Current CT technology allows for submillimeter isotropic
image reconstruction; that is, the production of volumetric data sets that have equal
submillimeter spatial resolution in all three planes. The management of these data requires very
high-quality computer processors, networking equipment, and data storage. These are critical
components in maintaining a successful CTA program. Software developments complement this
new imaging hardware, allowing for near-real-time image reconstruction of MPRs, curved
reformations, maximum-intensity projections (MIPs), and 3D volumetric images. These imaging
techniques enable optimized multiplanar visualization of relevant vascular anatomy often not well
represented by axial images alone.
Electronic networking has also facilitated the rapid distribution of the relevant image data to
image specialists for interpretation, and provides real-time online availability of formal written
reports to requesting physicians. At some institutions, the entire process of ordering,
interpreting, and reporting imaging studies is digital and paperless. This new technology
increases the efficiency of an imaging department while reducing errors and costs.
Reconstruction Intervals
A major advantage of multislice spiral technology over serial acquisitions is the ability to
reconstruct image data at various intervals, not just the acquired image thickness. Instead of
each reconstructed slice representing an entirely new volume of information, 64-slice scanners
use approximately 50% overlap at 1-mm intervals. Minimally overlapping image data allows for
improved image contiguity and high-quality images for CTA interpretation.
Multiplanar Reformations
MPRs are often performed in the sagittal and coronal planes as part of routine image
reconstruction. Coronal reformations of the pulmonary arteries are used to confirm small
pulmonary emboli. Sagittal and coronal reformations of the cervical spine and neck CTA are
routinely performed (Fig. 6-2). The use of routine MPRs is growing, and in many radiology sub-
specialties, coronal and sagittal reformatted images are provided as a part of other standard
CT protocols.
Image postprocessing workstations, either freestanding or packaged with Picture Archiving and
Communication System (PACS) applications, can be used for on-the-fly MPRs used for
troubleshooting or presenting cases to referring clinicians. Curved MPRs can demonstrate, with
a single image, multiple scan planes to demonstrate the tortuous course of a single vessel (Fig.
6-1).
Maximum-Intensity Projections
MIP is another effective way to display CTA data. The MIP algorithm takes a set of slices from
a volume and projects the maximum-density pixels above an arbitrary threshold onto a
composite image. This process essentially stacks the images on one another, creating a
visual sum of the densest structures into a single image for interpretation. The number of
images summed and the HU threshold can be adjusted for optimal image quality. In CTA, MIPs
are particularly useful, as the contrast-enhanced vessels are preferentially projected onto the
MIP image, making their tortuous course easier to follow. While there is no image subtraction
as is routinely practiced in MR angiography (MRA), there is the added effect of relative
subtraction of surrounding soft tissue. MIPs are routinely used for CTA of the head, as the
conspicuity of aneurysms and stenosis in and around the Circle of Willis is increased (Fig. 6-3).
Volume Reconstructions
Advances in computer processing speeds, software algorithms, and screen displays have
made 3D volume rendering an extremely valuable tool. With the advent of multislice technology
and thin collimation, the number of images being produced from a single CTA can approach
3,000. Although a vast amount of anatomic information may be present, only a very small piece
of information is present on each image. 3D volume rendering provides a visually efficient
display of a large amount of imaging data (Fig. 6-4). Also, volume rendering, because of its
anatomic authenticity, is an extremely useful method to communicate information to referring
clinicians. This is particularly true for vascular and cardiac surgeons, where understanding the
3D relationship of vital anatomic structures is essential to effective surgical management.
FIGURE 6-2. Left oblique 3D volume-rendered (A) and coronal MPR (B) images from a
neck CTA in a patient involved in a motor vehicle accident demonstrate a Type III odontoid
fracture (B; arrow) extending through the left transverse foramen with an intact vertebral
artery (A; arrow). CTA excludes vascular injury in patients with cervical spine fractures.
FIGURE 6-3. Coronal MIP image from a head CTA (A) shows an anterior-communicating
artery aneurysm (white arrow) as suspected by the noncontrast head CT (B) showing
subarachnoid hemorrhage in the suprasellar cistern with a central area of rounded low
attenuation (white arrow) suspicious for an aneurysm.
FIGURE 6-4. Three-dimensional reformatted image from a patient status post-coronary
artery bypass graft (CABG), including a left internal mammary (LIMA; arrow) graft to the
left anterior descending artery. This patient was scheduled for a second coronary bypass
due to recurrent stenosis. The 3D perspective offered from volume rendering allows the
surgeon to visualize the relationship between the LIMA graft and the posterior table of the
sternum and directs surgery. In this case, because of the proximity of the LIMA to the
sternum, the approach of the repeat sternotomy was altered. CT is performed for all redo
CABG patients in our practice, as it is our test of choice to determine the course and
caliber of bypass grafts.
Intravenous Contrast Administration and Timing

The use of IV contrast is critical for the proper evaluation of vascular anatomy and related
disease processes. End organ enhancement from the use of IV contrast also provides
diagnostic clues regarding vessel patency and effective perfusion. Multiphase or delayed
imaging may provide further diagnostic information regarding arterial extravasation and contrast
pooling related to vessel injury or delayed enhancement of certain tumors.
Given the small but definite risk of IV contrast material, careful assessment of potential
contraindications must take place by both the ordering physician and the facility imaging the
patient. While a complete discussion of iodinated contrast indications and contraindications is
beyond the scope of this chapter, many excellent educational resources on this topic exist
(11,12).
The first goal of contrast administration is obtaining IV access. When imaging the thoracic aorta
or great vessels, the right arm is the preferred IV site, as dense contrast material injected from
the left arm tends to opacify the left brachiocephalic vein at the time of image acquisition,
causing streak artifact and obscuring findings. High injection rates (>3 mL per second) are often
optimal for CT angiography, so an 18- to 20-G IV in the anticubital fossa is preferred. For more
routine imaging protocols of the abdomen or brain, a 22-G IV in the hand may be adequate. For
patients with central lines, ports, or peripherally inserted central catheters, the use of contrast
injection systems is potentially unsafe. Therefore, consultation of specific manufacturer
guidelines and individual departmental policies is highly recommended prior to use.
Once IV access is obtained, contrast can be administered with either a single- or a dual-head
injection system. Dedicated vascular protocols, such as those for coronary artery imaging,
benefit from the use of dual-head injectors in which the bolus of IV contrast is followed by
saline. The saline injection ensures a tight contrast bolus that can be optimally timed to image
the anatomy of interest.
Two methods ensure ideal contrast opacification to the anatomy of interest: (i) bolus tracking
and (ii) bolus timing. For bolus tracking, a noncontrast axial image is obtained through the
vessel of interest and a region of interest (ROI) is placed within. For imaging the thoracic aorta,
the ROI is placed in the aorta itself. For imaging the pulmonary arteries, the ROI is placed in
the main pulmonary artery. The entire bolus of contrast is then administered, and repetitive
images through the ROI are obtained while the progressive opacification is tracked within the
ROI using Hounsfield units. Once the ROI reaches a preset threshold (often 150 to 200 HU), a
scan of the entire area of interest is acquired. The benefits of using the bolus tracking technique
are ease of use and overall speed, as no extra steps are taken to ensure proper timing.
However, using this technique requires that every aspect of the IV placement, scan protocol,
and equipment be set up correctly the first time, with little room for error.
Bolus timing (also known as test bolus) uses prior knowledge of how long it takes the contrast
to go from the site of injection to the vessel of interest to accurately coordinate the scan with
the injection. This requires the use of a test bolus, or a separate small dose of contrast (usually
10 to 15 mL) injected while repeatedly imaging the vessel of interest. As in bolus tracking, the
ROI is placed on the vessel, but because the entire small bolus of contrast is given, the wash-
in, peak opacification, and washout of contrast can be retrospectively mapped as an
enhancement-versus-time curve. The peak opacification time is then used as the delay time
between contrast injection and commencement of the scan. The test bolus and main injection
rates should be identical, and when a dual injection system is used, identical amounts of saline
should be used to ensure a representative test bolus.
One major advantage of the test bolus technique is that it not only ensures imaging at peak
enhancement, but also acts as a test run for the patient, CT technologist, and equipment. This
assures that the IV is functional and lets the patient become accustomed to the feeling of the
contrast and saline injections, which may otherwise startle or surprise the patient, a reaction
that can lead to increased patient motion and degraded image quality. Once mastered, this
technique can be used for planning arterial or venous phase imaging of any vessel, from the
pulmonary or coronary arteries to the portal or hepatic veins.
CLINICAL APPLICATIONS
Introduction
CT is now the most widely used modality for arterial imaging, and continuing advances in spatial
and temporal
resolution, combined with the improved delivery of contrast and widespread availability of the
technology, will only increase the number of applications. As in all imaging modalities, the
success of CT relies on the ability of the imager to carefully follow CT protocols and to
communicate with the referring clinician.
With respect to vascular CT protocols, strict adherence to the parameters (e.g., pitch,
collimation, slice thickness, contrast injection rate and timing, IV site, ECG gating, patient
position, reconstruction algorithms, and reformations) is more important than in solid organ
imaging because of the added importance of reducing motion and carefully timing the contrast
bolus. Communication is critical both before and after the examination, and it remains the
responsibility of the imager not only to educate referring clinicians, but also to ensure, on a
case-by-case basis, that the imaging focuses on the clinical problem. For example, chest pain
that is pleuritic with dyspnea and positive D-dimer would be imaged using a protocol designed
to detect pulmonary emboli, which is dramatically different from the dissection protocol that
would be used to image chest pain accompanied by a tearing sensation and discordant left
and right arm blood pressures.
One of the most common questions in vascular imaging is CT versus MRI. It is still true that the
choice of modality depends on the availability of the equipment and the experience of the
imager. However, as many imaging centers become equipped with modern CT and MRI,
recommendations become more important. The advantages of CT over MRI are the speed of
the examination and, in general, superior spatial resolution. Imaging an unstable patient is much
simpler with CT, and claustrophobia is rarely an issue since the gantry of a CT is typically far
shorter and more open than the bore of a MRI. Also, patients with pacemakers can be imaged
with CT. An advantage of MRI is that gadolinium is less nephrotoxic than iodine, and for patients
with severe allergies, the superior tissue contrast of MRI often enables a diagnosis without
contrast.
While patient factors can play a role in determining the modality, calcification and the size of the
vessel lumen are also important. In the aorta, where the lumen is wide and the detection of
displaced calcium can be a clue to diagnosis, CT is preferred because the clinical problems
(dissection, aneurysm, penetrating ulcer) usually do not involve the grading of stenosis. In
smaller vessels such as the renal, mesenteric, and calf arteries, determining the patency and
degree of stenosis is usually the primary clinical question. Imaged patients often have
significant atherosclerotic disease, and the presence of calcium induces artifacts that routinely
cause the stenosis to be overestimated. In MRI, the same calcification can induce susceptibility
artifact, however, high-resolution MRI is, in our experience, more effective in grading stenosis in
small vessels. For this reason, in the authors' practice, CT is not routinely used for renal artery
stenosis or for runoffs. As detailed below, the most robust modality for noninvasive coronary
imaging is ECG-gated MDCT. However, the interpretation of coronary CTA can be
compromised by the presence of dense coronary calcification.
Aorta
Historically, evaluation of the aorta has progressed from catheter angiography to modern CT
aortography (Fig. 6-5). The current standard of care is MDCT with ECG gating, and this
examination has virtually replaced catheter angiography in the assessment of the aorta.
Moreover, the ability of ECG gating to eliminate motion in the ascending aorta has eliminated
the need for transesophageal echocardiography (TEE).
CTA of the aorta should be preceded by a noncontrast acquisition to detect small intramural
hematomas, periaortic hematomas from a leaking aneurysm, displaced intimal calcifications,
and postsurgical material. Because of its high attenuation in comparison with soft tissue, these
findings can be masked by contrast administration. Iodinated contrast medium is then delivered
by a power injector at a rate of >3 mL per second and bolus tracking is used to time the scan.
To evaluate organ perfusion and venous structures, a third acquisition can be added with a 60-
second delay. This delayed scan helps to detect slow flow in a false lumen of a dissection that
can be mistaken for thrombosis during the arterial phase of enhancement. It also allows for the
detection of small endoleaks or end organ ischemia that may be apparent only on delayed
images.
Postprocessing is routinely performed to better delineate the arch vessel origins, branch
vessels, surrounding anatomy, and to allow for precise measurements. A typical case may use
any combination of MPRs, MIPs, and 3D volumetric reconstructions. Thin collimation is required
for high-quality reformations and 1-mm slices are usually sufficient for defining aortic pathology.
Modern CT scanners enable the operator to scan with submillimeter isotropic resolution. This is
important in cardiac applications because the coronary arteries have a diameter of
approximately 3 mm. Consequently, if 1-mm slices were used for interpretation, the coronary
artery would span at most 3 pixels without volume averaging. Since stenosis quantification is
critical in coronary artery disease imaging, thinner slices are required. However, the use of
thinner slices means longer scan times and longer breath holds. For imaging the entire thoracic
aorta, using the thinnest slices may permit the highest-quality reformatted images, but the long
scan time then required would be likely to introduce breathing motion artifacts in some patients.
The diagnostic strength of contrast-enhanced ECG-gated CT aortography is its ability to
distinguish among aneurysm types, penetrating ulcers, dissection, and aortic rupture. Both
saccular-type aneurysms and penetrating ulcers are characterized by a focal outpouching of
contrast material (Fig. 6-6), but CT readily distinguishes them. In a saccular aneurysm, the
focal outpouching has a wide neck and typically the contrast does not course through a region
of thrombus. A penetrating ulcer often has a narrow neck and is more focal, and the contrast
often penetrates into the region of thrombosis.
In patients with aneurysms, accurate measurements are important because the risk of rupture
is related to size. The advantage of CT over catheter aortography is that the latter images only
the lumen and thus underestimates the true aortic diameter. Since axial images overestimate
aortic diameter when the aorta is tortuous, MPRs are important for precise measurements. CT
is also the best method to assess interval change. Finally, in symptomatic patients, CT allows
for rapid diagnosis of rupture seen as contrast extravasation and/or para-aortic hematoma (Fig.
6-7).
Penetrating ulcer is defined as an ulcerating atherosclerotic lesion that penetrates the internal
elastic lamina, allowing for hematoma formation within the aortic wall, usually within the media
(13). Penetrating ulcers occur in patients with advanced atherosclerotic disease and appear as
focal intimal defects with adjacent subintimal hematoma, often in a region of atherosclerotic
plaque. In these cases, clinical presentation is the most important factor in patient
management, with symptomatic ulcers typically requiring intervention. However, changes in
ulcer size and morphology can guide treatment options, since ulcers that have a diameter >20
mm and depth >10 mm have a very high risk of progression.
Intramural hematoma (IMH) is thought to represent rupture of the vasa vasorum. Its
management remains controversial, probably because IMH may be the manifestation of
aneurysm, penetrating ulcer (Figs. 6-8 and 6-9), dissection, or aortic rupture (Fig. 6-7). It is not
controversial that CT is the diagnostic study of choice and noncontrast imaging has a sensitivity
and specificity approaching 100%. IHM is seen as a hyperdense, crescentic, or circumferential
collection in the aortic wall, often without significant narrowing of the adjacent aortic lumen (Fig.
6-10) (13). IMH also maintains a constant relationship with the aortic wall, as opposed to the
spiraling seen with aortic dissection. IMH does not enhance, and when enhancement is seen,
an alternative diagnosis should be made. The same acquisition can be used to detect and
characterize abdominal involvement such as branch vessel dissection, occlusion, and visceral
infarcts (Fig. 6-11). When followed by serial CTA, IMHs usually resolve; however, complications
such as progression to dissection can occur (Fig. 6-11).
FIGURE 6-5. Aortic imaging has progressed from invasive catheter angiography (A), to
helical single-row CT (B), to nongated multidetector CT (C), to ECG-gated multidetector
CTA (D).
FIGURE 6-6. Two images from an ECG-gated thoracic aortic CTA show an example of a
wide neck saccular-type aortic arch aneurysm (A; white arrow) and a penetrating
descending aortic ulcer (B; black arrow).
FIGURE 6-7. Four ECG-gated thoracic aorta CTA images from a 72-year-old patient who
presented with acute chest pain and hypotension show a ruptured aortic aneurysm with
intramural hematoma (white arrow) and hemothorax (black arrow). CTA allows for rapid
diagnosis and definitive management in patients with life-threatening disease processes.
FIGURE 6-8. A, B: Two images from ECG-gated aortic CTA exams show examples of
penetrating aortic ulcers, each leading to intramural hematoma (white arrows).
FIGURE 6-9. Coronal oblique image from an ECG-gated aortic CTA shows a focal area of
contrast extravasation into the aortic wall (white arrow) consistent with an aortic ulcer with
secondary circumferential high attenuation (black arrows) within the aortic wall consistent
with an intramural hematoma (IMH).
Aortic dissection is caused when a breach of the intima leads to intravascular blood separating
the intima from the media, creating an intimal flap. Among CT, MR, and TEE, ECG-gated
MDCT has the advantage of speed, availability, and superior sensitivity and specificity for
visualizing the intimal flap separating the true lumen from the false lumen (Fig. 6-12). The false
lumen can have a variable appearance and may opacify completely, partially, or, if thrombosed,
not at all. The high signal, contrast, and spatial resolution of CT enable classification between
Type A and Type B dissection, the principal criterion for determining surgical versus medical
intervention. In all cases of Type A dissection, it is important to determine the relationship of the
intimal flap to the coronary arteries, great vessels, and visceral branches, as occlusion can
have potentially fatal complications (Fig. 6-13).
Head and Neck Computed Tomographic Angiography
As the third leading cause of death in the United States, with an estimated 750,000 cases
annually, stroke represents a significant clinical indication for vascular imaging. The typical
evaluation includes noncontrast head CT followed by a detailed study of the neurovascular tree.
While MRI and MRA have been routinely used, CTA is gaining favor, in part because of its
widespread availability, speed, and ease of use. The duration of the CT acquisition is <30
seconds, limiting motion from patients who can, because of the nature of the disease, be
noncompliant.
FIGURE 6-10. A: Noncontrast axial image from an ECG-gated aortic CTA shows
circumferential high attenuation (white arrow) within the aortic wall consistent with an
intramural hematoma (IMH). B: The IMH is subtler on the contrast-enhanced image and
can sometimes be masked by the use of contrast. This is the primary reason why
noncontrast acquisitions are routinely obtained initially when evaluating the aorta.
In a typical head and neck CTA for stroke, 100 to 125 mL of 300 to 370 mgI/mL contrast
material is administered IV at 3 to 4 mL per second. The acquisition is caudal to cranial,
beginning at the aortic arch through the brain to assess both the neck and the intracranial
vasculature. CTA in cases of subarachnoid hemorrhage is usually performed only through the
brain to evaluate for intracranial aneurysms. Collimation is typically submillimeter, with pitch <1
for adequate oversampling. A timing delay of 15 to 20 seconds provides good arterial and early
venous phase images. Multiplanar MIPs and thin axial source images are used for interpretation
of vessel course, caliber, patency, and associated disease.
Head and neck CTA provides needed information required for stroke management. Namely,
hemorrhage and mass lesions can be excluded and vessel patency can be assessed. The
sensitivity and specificity for large vessel occlusion approach those of digital subtraction
angiography (DSA), with CTA demonstrating 99% to 100% accuracy for detecting occlusions of
the internal carotid artery, middle cerebral artery, and basilar artery (14, 15, 16, 17) (Fig. 6-
14). The exam studies not only the vessels, but also the wall and surrounding structures.
Inclusion of the neck means detailed characterization of the carotid arteries, particularly the
bifurcation, without Doppler ultrasound. In fact, there are some reports that claim plaque
calcification, size, and ulceration can be better assessed by CTA than DSA (18). In addition,
grading of stenosis and detection of carotid dissection or occlusion are possible (Fig. 6-15).
As in other body parts, one disadvantage of CTA is that it requires iodinated contrast material,
limiting its use in patients with allergies and renal failure. In addition, dynamic assessment of
flow velocities is not available, a certain advantage of Doppler ultrasound. Finally, with respect
to detection of acute infarcts, the sensitivity of diffusion-weighted MRI is far superior to that of
CT. However, CT perfusion imaging protocols may ultimately compete with MRI and, in
addition, may add further diagnostic information regarding cerebral blood flow, cerebral blood
volume, and mean transit time (19).
In patients with subarachnoid hemorrhage, CTA can effectively diagnose intracranial
aneurysms. While DSA remains the gold standard, high-spatial resolution MDCT remains
appealing for screening, as it is noninvasive and can readily exclude other pathology. CTA has
demonstrated a high sensitivity and specificity, detecting 98% to 100% of aneurysms of <4 mm
(20,21). MIP images are particularly useful for aneurysm detection, since interpretation based
on axial source images alone may underestimate or overlook an abnormality. Circle of Willis
aneurysms can be easily characterized for location, size, and surrounding vessels that might
complicate surgical clipping (Fig. 6-3). Further, 3D postprocessing more fully characterizes
lesions and the surrounding anatomy for improved surgical or interventional planning. After
treatment, CTA is useful to exclude complications such as vasospasm or infarct.
Less common lesions can also be characterized; in some cases, protocols should be modified
to account for the pathophysiology of the disease. For example, when imaging areteriovenous
malformations (Fig. 6-16), increasing the delay time or performing a second delayed acquisition
allows for contrast opacification of the dural venous sinuses. Called CT venography, this
technique can also be used for the detection of dural venous sinus thrombosis (Fig. 6-17).
Pulmonary Arterial Imaging

Pulmonary embolism (PE) represents the third most common cause of acute cardiovascular
disease after myocardial infarction and stroke, with an estimated 175,000 new cases each
year (22). The clinical presentation of PE is variable, and thus history and physical exam are
quite insensitive. Untreated PE has a mortality rate that can approach 30%, and thus accurate
imaging of PE is paramount. Before MDCT became routinely used, DSA was the gold standard.
However, DSA is invasive and expensive, suffers from high interobserver variability, and is often
impractical and/or unavailable. CT pulmonary angiography (CTPA) is superior to DSA and
nuclear medicine for routine cases. Sensitivities and specificities for lobar, segmental, and
subsegmental PE (in studies performed after 2000) range from 70% to 97% and from 86% to
100%, respectively (22, 23, 24). In addition, the very high negative predictive value (up to 99%)
plays an essential role in safely discharging emergency room patients. Finally, CTPA images
are reconstructed with a full FOV to detect other causes for patient symptoms such as
pneumonia, aortic dissection, and rib fractures.
FIGURE 6-11. Axial (A, B) and coronal MPR (C) images from an ECG-gated aortic CTA in
a patient with mild chest pain show an intramural hematoma (white arrows) involving the
descending thoracic and abdominal aorta complicated by partial infarction of the left kidney
(white dashed arrow) from ostial narrowing and emboli (not shown). D: A sagittal MRP
image obtained 3 months later shows interval development of an aortic dissection with a
prominent intimal flap (white arrow). This case illustrates the continuum of intimal injury that
represents intramural hematoma, dissection, and penetrating ulcers. Incidental note is
made of secondary celiac and superior mesenteric artery stenosis (white dashed arrows)
and a right renal stent (black arrow) that was placed to protect the only remaining renal
ostium.
FIGURE 6-12. Coronal MPR image from an ECG-gated aortic CTA demonstrates an
intimal flap (black arrow) in a patient with Type B aortic dissection.
FIGURE 6-13. Axial (A) and sagittal (B) images from an ECG-gated aortic CTA show an
intimal flap (black arrow) in close proximity to the right coronary artery ostium (white
arrow) in a 65-year-old male with a known ascending aortic aneurysm who presented with
acute chest pain. Invasive coronary angiography (not shown) confirmed the lack of
involvement of the right coronary artery; however, high-quality CTA exams are now
obviating the need for invasive methods of confirmation.
FIGURE 6-14. Axial MIP image from a head and neck CTA performed in a 51-year-old
diabetic with right hemiparesis shows an abrupt cutoff of the right MCA, M1 segment
(white arrow). CTA is now routinely used in the acute clinical setting for the rapid and
accurate assessment and management of stroke patients.
FIGURE 6-15. Sagittal MIP images from a head and neck CTA in two separate patients
show a long segment carotid dissection (A; white arrow) and a carotid occlusion with
luminal thrombus (B; white arrow) in two patients presenting with acute stroke symptoms.
FIGURE 6-16. Sagittal MIP image from a head CTA (A) provides excellent characterization
of a large arteriovenous malformation with areas of aneurysm compared with conventional
invasive angiography (B). (Case courtesy of Christos Gkogkas, M.D., Department of
Radiology, Brigham & Women's Hospital and Harvard Medical School, Boston,
Massachusetts.)
FIGURE 6-17. Sagittal MIP (A) and sagittal oblique 3D volume-rendered (B) images show
occluding thrombus (white arrows) in the anterior aspect of the superior sagittal sinus with
return of normal flow more distally (black arrow) in a 28-year-old pregnant female
presenting with acute stroke symptoms consistent with venous thrombosis. C: Noncontrast
head CT on presentation shows the classic findings of bilateral frontal lobe hemorrhagic
infracts. (Case courtesy of Cheryl A. Sadow, M.D., Department of Radiology, Brigham &
Women's Hospital and Harvard Medical School, Boston, Massachusetts.)
CTPA is reliable and easy to perform. Bolus tracking with a main pulmonary artery ROI is
standard. Typically, 100 mL of 370 mgI/mL iodinated contrast material is injected at a rate of 3-
4 mL per second. Thin collimation images (1 mm) increase the sensitivity and specificity
(25,26). Reconstructing images with some overlap ensures complete visualization of the
pulmonary arterial tree. The diagnosis is made when a low-attenuation filling defect is seen in
the pulmonary arteries (Fig. 6-18A and B). Many protocols include CT venography, or the
delayed imaging (2 to 4 minutes) of the pelvis and lower extremities to detect deep vein
thrombosis (DVT) (Fig. 6-19) (26, 27, 28, 29, 30). In the setting of a negative CTPA, the
presence of DVT may still warrant anticoagulation.
CTPA, as the new standard of care, is being used for patient outcomes studies. Morbidity and
mortality from PE comes from failure of the right ventricle (RV). Traditionally, the RV has been
studied with echocardiography. However, the RV is fully imaged with CTPA, and there is
increasing evidence that dilatation of the RV seen on CTPA (Fig. 6-20) can be used to
determine the subset of patients for whom more aggressive treatment (e.g., thrombolysis and
thrombectomy) is warranted (31, 32, 33).
FIGURE 6-18. A: Thin collimation axial image from a CT pulmonary angiogram (CTPA)
shows large bilateral filling defects within the pulmonary arteries (white arrows) consistent
with acute pulmonary emboli. B: These are also visualized by the coronal MPR (white
arrows), a plane that may be more sensitive to detecting smaller emboli.
FIGURE 6-19. CT venography shows filling defects (white arrows) within bilateral popliteal
veins consistent with deep vein thromboses (DVT) and is easily performed at the same
time as CTPA using a delayed acquisition through the pelvis and thighs.
FIGURE 6-20. ECG-gated axial CTA image shows dilatation of the right ventricle, a finding
shown to be a poor prognostic indicator in patients with acute pulmonary emboli.
FIGURE 6-21. Axial (A) and sagittal (B) MIP images from an ECG-gated thoracic aorta
CTA show a patent ductus arteriosis (white and black arrows) in a 45-year-old woman with
dyspnea and an abnormal echocardiogram.
CTA is also an ideal tool for evaluating any number of vascular entities in the chest. Whether
evaluating congenital vascular anomalies (Fig. 6-21), iatrogenic complications (Fig. 6-22), or
staging tumors, CTA is a flexible and powerful tool with high diagnostic accuracy.
FIGURE 6-22. Coronal MPR from a chest CTA shows a calcified catheter fragment in the
left brachiocephalic vein (white arrow).
Computed Tomographic Pulmonary Venography

Atrial fibrillation is one of the most common cardiac arrhythmias, affecting approximately 2.5
million people in the United States alone. Ectopic arrhythmogenic foci in the central pulmonary
veins represent a major source of atrial fibrillation. Radiofrequency catheter ablation of these
foci successfully cures atrial fibrillation in 50% of patients. Prior to ablation, a detailed map of
the left atrium and pulmonary veins is required to guide the procedure. CT pulmonary
venography (CTPV) provides this detail and is as easy as CTPA to perform. CTPV has proven
far more accurate than intracardiac and transesophageal echocardiography, as well as invasive
venography, in defining the number of pulmonary veins (34). In addition, pulmonary vein
anomalies are better detected by CTPV than intracardiac echocardiography (35). MRI can also
be performed in patients unable to receive iodinated contrast.
Pulmonary vein and left atrium imaging relies on maximal contrast opacification; thus, accurate
timing is again essential. As discussed in detail elsewhere, imaging the beating heart requires
ECG gating, thin collimation (<1 mm), and oversampling (pitch, <1). CTPV is performed using
bolus tracking, with the ROI on the left atrium. A higher injection rate of 4 to 5 mL per second
and 370 mgI/mL iodinated contrast material ensures ideal contrast opacification of the left
atrium. The craniocaudal anatomic range can be tailored to cover just the main and segmental
pulmonary venous branches.
The imaging goals of CTPV are to identify the pulmonary veins and branches, measure their
dimensions, create a 3D roadmap for use during the procedure, and create a baseline for
follow-up. The left superior pulmonary vein is of major interest, as it represents the site of
ectopic foci in 50% of patients. MPRs as well as 3D surface renderings are routinely used and
provide the interventional team with a 3D perspective of the anatomy (Fig. 6-23). CT can also
be used in follow-up to evaluate for complications such as pulmonary vein stenosis (36).
FIGURE 6-23. A 3D volume-rendered image of the left atrium in a patient with atrial
fibrillation performed prior to ablation of ectopic foci in the pulmonary veins. 3D images
enable complex anatomic information to be easily conveyed to and understood by referring
physicians.
Abdominal and Pelvic Vasculature

CTA has expanded beyond imaging the aorta, and common indications now include the
evaluation of acute and chronic mesenteric ischemia, renal artery stenosis, healthy donor and
recipient liver and renal transplants, and trauma, and for general presurgical planning. In
addition, the expanding role of CT for oncologic indications has made CTA a valuable tool for
staging, determining resectability, planning surgical interventions, and following potential
treatment complications.
Mesenteric Computed Tomographic Angiography

Acute and chronic abdominal pain caused by mesenteric ischemia is a complex diagnosis.
Classic history and exam findings (abdominal pain out of proportion to physical exam findings,
nausea, anorexia, vomiting, and bloody diarrhea) are unreliable and nonspecific. Acute
mesenteric ischemia is caused by arterial thrombosis in 50% of cases, from either local
atherosclerotic disease or proximal emboli. Nonocclusive atherosclerotic disease, venous
thrombosis, and systemic hypoperfusion are less common etiologies (37,38).
Since MDCT offers arterial and venous imaging with detailed assessment of the bowel itself, its
use has increased dramatically. Moreover, alternate (i.e., nonvascular) causes of abdominal
pain are identified, as the study is routinely reviewed as an abdomen/pelvis CT. Because the
mesenteric vessels are small and the detection of embolism is critical, the thinnest collimation
available should be used. Bolus tracking on the abdominal aorta is used and delayed imaging is
performed to assess organ perfusion and major veins. Oral contrast is not typically used in the
urgent setting. In the nonemergent workup of subacute or chronic mesenteric ischemia, 750 to
1,000 mL of a neutral contrast agent (e.g., water or methylcellulose solution) given by mouth
provides uniform bowel distension and a better evaluation of secondary intestinal findings.
FIGURE 6-24. Sagittal MPR from a mesenteric CTA shows significant atherosclerotic
stenosis of both the celiac (white arrow) and the superior mesenteric arteries in a patient
with chronic intestinal angina.
There are direct and indirect findings in mesenteric ischemia. Direct findings include an
occlusive or subocclusive thrombus or an abrupt cutoff. Atheroma, calcified or not, may also
represent a chronic cause of intestinal angina (Fig. 6-24). Finally, narrowing or occlusion
caused by surrounding or invasive tumor represents a rare cause of ischemia. Indirect findings
include bowel dilatation, wall thickening, decreased mucosal enhancement, pneumotosis
intestinalis, and portomesenteric or portovenous gas (39, 40, 41).
CTA is also an excellent tool to diagnose other vascular disease of the mesentery such as
median arcuate ligament syndrome (Fig. 6-25), superior mesenteric artery syndrome, and
visceral aneurysms such as splenic and renal artery aneurysms (Figs. 6-26 and 6-27). Other
indications include preoperative vascular mapping for a variety of surgeries, including liver
transplantation (41, 42, 43) and gastric surgery (44).
Renal Computed Tomographic Angiography

Renal vascular anatomy can be routinely evaluated with CTA. However, for a patient with
underlying atherosclerosis and hypertension, high-resolution renal MRA is preferred to CTA.
The rational for MRA in these patients is the fact that the renal ostia and proximal renal arteries
are often heavily calcified. In vessels with a small diameter (<5 mm), the high density of
significant calcification can lead to an overestimation of stenosis. Moreover, in cases where the
volume of calcium is large, interpretation is difficult. While the details of MRA are beyond the
scope of this chapter (see Chapter 10), in most cases, modern contrast-enhanced renal MRA
is able to overcome these problems. In cases where significant calcification is not expected, or
in patients with a contraindication to MR, CT is useful. CTA is routinely used for evaluating
healthy potential renal donors, renal artery aneurysms (Fig. 6-26), dissection, thrombosis, and
arteriovenous malformations. Standard protocols involve arterial and delayed venous phases.
Sagittal and coronal MPRs, MIPs, and curved reformatted images allow for detailed evaluation
of the renal vasculature in the optimal imaging planes.
FIGURE 6-25. Sagittal MIP (A) and 3D volume-rendered (B) images from a mesenteric
CTA show focal narrowing and abrupt angulation of the proximal celiac artery (arrows) in a
25-year-old female with intermittent intestinal angina and an abdominal bruit diagnostic for
median arcuate ligament syndrome.
FIGURE 6-26. A: Axial image from a mesenteric CTA shows a focal area of contrast in the
splenic fossa along the splenic artery consistent with a splenic artery aneurysm (white
arrow). Coronal thick slab MIP (B) and 3D volume-rendered (C) images demonstrate the
location of the aneurysm (white arrows) and its relationship to the surrounding vasculature
for precise surgical or interventional management.
FIGURE 6-27. A: Axial image from an arterial phase renal CTA shows a focal collection of
contrast adjacent to the left kidney (white arrow) in a 68-year-old patient with acute
abdominal pain suggesting a ruptured pseudoaneurysm. B: Angiogram confirms this finding
(black arrow) and demonstrates successful coiling (C: black arrow). A follow-up CTA
shows the embolic material with no further active bleeding (D: white arrow).
For potential renal donors CTA allows for the detailed assessment of the number, length, and
course of renal arteries and veins (45, 46, 47). This information is crucial to preoperative
planning, as renal vascular anatomic variations such as retroaortic left renal veins (Fig. 6-28)
are present in 25% to 30% of patients (47). Curved MPRs provide the most reliable
measurements. In addition, CT provides information about renal size, position, potential
anomalies (e.g., duplicated or horseshoe kidneys), or mass lesions (neoplastic or large cysts)
that may alter the eligibility, surgical approach, or choice of kidney for donation.
Oncologic Computed Tomographic Angiography

CTA has improved the ability to stage tumors, plan surgery, and assess treatment
complications. For staging and surgical planning, CTA in the liver, kidney, and pancreas has
proven particularly useful since the complex local vascular anatomy and potential for vascular
involvement greatly affect the resectability and surgical approach. For example, when
multiphase CT is used to determine that a liver mass represents a malignancy, assessment of
the portal and hepatic veins is essential for staging and planning potential intervention. Fewer
than 10% of patients with hepatocellular carcinoma can be treated with conventional hepatic
resection. For hepatocellular carcinoma unresectable due to stage or various comorbidities,
CTA can be used to delineate the hepatic arterial supply and segmental anatomy for alternative
treatments such as chemoembolization and ablation (48,49).
CT can also be an important part of the evaluation of renal masses. For example, when renal
cell carcinoma is suspected, evaluation of the ipsilateral renal vein is necessary to exclude
vascular invasion. If the renal vein is involved, then evaluation of the IVC is also crucial, as these
lesions may track up the IVC to the right atrium, requiring the assistance of cardiothoracic
surgery for resection. When certain renal masses are small and show no evidence of vascular
invasion, CTA provides a detailed view of the anatomy that may allow for a nephron-sparing
partial nephrectomy (50,51).
Thin collimation CTA for patients with pancreatic neoplasms has proven effective in
characterizing tumors and determining their relationship and involvement with surrounding
vessels (52, 53, 54, 55, 56). Involvement of adjacent vascular structures, particularly the
superior mesenteric artery, often limits respectability and CTA provides the high-quality images
and vascular detail necessary to stage these tumors appropriately.
FIGURE 6-28. Thick slab MIP (A) and 3D volume-rendered (B) images from a healthy
renal donor show normal single renal arteries bilaterally and a retroaortic left renal vein
(white arrow). Detecting renal artery or renal vein anomalies may significantly alter the
eligibility or surgical approach in these cases.
Peripheral Arterial Imaging

The three most common applications for the imaging of peripheral arteries are trauma,
extremity aneurysm, and runoff exams for atherosclerotic peripheral arterial disease (PAD),
with the latter being by far the most common. Because it offers the highest spatial and
temporal resolution, catheter angiography remains the gold standard for peripheral arterial
imaging, and pressure gradient measurements are the best method to determine
hemodynamically significant atherosclerotic lesions. However, because catheter-based imaging
is invasive, noninvasive tests, such as CTA, play a significant role and provide high-quality
images (Fig. 6-29). The workup for PAD typically begins with ultrasound to determine inflow
versus outflow disease. As discussed in another chapter, MRI has made a significant
contribution and, in most cases, can fully characterize the type of surgical management
necessary. However, certain contraindications to MR exist and CTA provides a noninvasive
alternative that offers excellent images when the degree of calcification is modest. Again, thin
collimation images from the pelvis through the lower extremities with multiplanar and 3D
reformations provide for high-quality images and excellent diagnostic accuracy.
In trauma patients, extremity CTA is the imaging modality of choice. CT rapidly and
noninvasively provides diagnostic information for clinical decision making, often obviating the
need for invasive angiography. Traumatic injury can be blunt or penetrating, and in addition to
making a noninvasive vascular diagnosis, bone and soft tissue injuries are simultaneously
assessed (Fig. 6-30).
CTA is also the modality of choice for imaging extremity aneurysms (Fig. 6-31). While MRI can
also be used, positioning the patient for extremity imaging is far simpler in CT than MRI, and
the CT exam can be performed much more quickly, increasing patient comfort.
FIGURE 6-29. Volume-rendered image from a runoff CTA shows normal pelvic and thigh
arteries.
FIGURE 6-30. Volume-rendered (A) and sagittal MPR (B) images from a runoff CTA show
a small focal pseudoaneurysm and intimal flap (arrows) in the popliteal artery in a patient
who suffered a severe tibial plateau fracture/dislocation injury of the knee in a skiing
accident.
FIGURE 6-31. Coronal MIP image from an upper extremity CTA show an ulnar artery
aneurysm in a patient with hypothenar hammer syndrome.
FIGURE 6-32. A 3D volume-rendered image of the upper extremity CTA runoff performed
on a 64-slice scanner shows a patent bypass graft, eliminating the need for further
evaluation by conventional angiography.
FIGURE 6-33. Volume-rendered image from a runoff CTA performed on a 64-slice scanner
shows no significant atherosclerotic disease without apparent focal stenoses and a
bilateral three-vessel runoff.
FIGURE 6-34. A: Coronal MIP image from a runoff CTA performed on a 64-slice scanner
shows significant calcified atherosclerotic disease bilaterally. The presence of calcium
somewhat limits the evaluation of vessel patency as noted on the volume-rendered images
(B).
FIGURE 6-35. Axial MIP image from a coronary CTA shows complex plaque in the
proximal left anterior descending coronary artery. Complex plaque includes both calcified
and noncalcified components.
While upper (Fig. 6-32) and lower (Fig. 6-33) extremity atherosclerotic PAD can be imaged with
CT, dense calcification routinely seen in patients with significant PAD can limit the examination
(Fig. 6-34). Therefore, MRI remains the noninvasive imaging method of choice, as it is better
able to determine severity of stenosis and map out the ideal vascular anatomy for intervention.
FIGURE 6-36. MIP image from a coronary CTA in a 17-year-old patient with evidence of
coronary ischemia shows a weblike stenosis in the origin of the left main coronary artery
(white arrow) that made selective catheterization impossible.
FIGURE 6-37. Axial images from an ECG-gated chest CTA in a patient with non-small cell
lung cancer and progressive heart failure. The patient has a cardiac pacemaker (white
dashed arrows) and thus MRI was contraindicated. Images show multiple low-attenuation
lesions (white and black arrows) with diffuse involvement and expansion of the
myocardium. Although uncommon, this appearance is characteristic for necrotic metastatic
disease to the myocardium. (Case courtesy of Scott A. Koss, M.D., Director of
Cardiovascular Imaging, Radiology Waukesha, Waukesha, Wisconsin.)
FIGURE 6-38. Axial noncontrast (A) and axial and short axis contrast-enhanced (B, C)
images from an ECG-gated coronary CTA demonstrate evidence of myocardial thinning
along the apical septum and calcifications (black arrows) consistent with an old myocardial
infarction. MRI was contraindicated due to the patient's pacemaker (white dashed arrows).
Cardiac Imaging
Cardiac CT pushes the limits of technology, using the thinnest slices, the fastest gantry rotation
times, the maximum slices per gantry rotation, and ECG gating. CT of the heart can be
routinely performed and CT is by far most robust modality to image the coronary arteries
noninvasively (Fig. 6-35). The protocol details for cardiac, specifically coronary, CTA are
beyond the scope of this chapter (57). However, for most cardiac CT examinations,
pretreatment with IV -blockade (for heart rate control) and sublingual nitroglycerine (for
vasodilation) is routine.
In addition to the evaluation for coronary artery disease, CT can be used in cases where
coronary catheterization is difficult or impossible (Fig. 6-36) and for imaging bypass grafts (Fig.
6-4). ECG-gated CT can also be used to image the myocardium (Figs. 6-37 and 6-38),
although in general cardiac function is best assessed with MRI in patients without
contraindications. For these imaging applications, intravenous contrast should be administered
at rates of 5 mL per second with a dual injection system, followed by saline. Saline is used to
avoid dense opacification of the right heart and potential artifacts that can limit interpretation of
the right coronary artery. In addition, the injection of saline after iodinated contrast pushes the
iodinated contrast to its anatomic destination and helps to minimize dilution of the contrast as it
passes through the central veins.
CONCLUSIONS
As the most robust modality to image the aorta and pulmonary circulation, CT has
revolutionized diagnoses and management decisions. For head and neck vascular imaging, CT
utilization is increasing, despite the fact that infarct imaging is best performed with MRI. In the
mesentery, CT can provide accurate vascular diagnoses for a large number of problems, and
high-quality imaging of the abdomen and pelvis can be beneficial for many patients. The
evaluation for renal artery stenosis and for runoffs is still best performed with MR, but CT can
be used in patients with a contraindication to MR. It is extremely important to estimate patient
radiation dose, to put dosimetry considerations in perspective, while imaging with a
multidetector CT scanner.
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> Table of Contents > Section II - Vascular Imaging > Chapter 7 - Magnetic Resonance Angiography
Chapter 7
Magnetic Resonance Angiography
Hale Ersoy
Frank J. Rybicki
Martin R. Prince
Recent improvements in magnetic resonance (MR) imaging technology and image processing
tools have enabled MR angiography (MRA) to evolve into one of the most commonly applied
noninvasive diagnostic methods. Currently, MRA has supplanted intra-arterial digital subtraction
angiography (DSA) for many clinical applications. MRA does not utilize x-rays, for which the
radiation can be substantial, particularly when diagnostic DSA is combined with endovascular
interventions. MRA is a reproducible non-invasive imaging technique, thus well suited for
conditions requiring frequent follow-up imaging. MRA avoids potentially nephrotoxic iodinated
contrast agents, which is especially important considering the patient population with
atherosclerotic disease. Most patients with atherosclerotic disease have at least some degree
of renal impairment and, thus, are more vulnerable to the nephrotoxicity associated with the
iodinated contrast agents. On the other hand, Gd-chelates are recently suggested as a
possible etiology of Nephrogenic Systemic Fibrosis in patients with renal failure (1a.) This
disorder predominantly involves the skin, but it may also affect other organs such as the lungs,
liver, muscle, and the heart in patients with renal failure. Recently researchers have
documented the presence of gadolinium in biopsy specimens of patients with NSF (1b,1c).
Although there are numerous remaining questions concerning the mechanisms involved,
participant radiologists are obliged to follow the recommendations of the FDA and other
leadership groups in our field.
Several MRA techniques (e.g., pulse sequences; see Table 7-1) are available to acquire high-
spatial resolution images of the vessel lumens, analogous to DSA. MR image contrast is
determined by the difference in signal intensity between the adjacent tissues. MR pulse
sequences differ from each other based upon their contrast mechanisms. Some pulse
sequences emphasize the differences in proton densities or magnetic relaxation times of the
tissues, such as T1- and T2-weighted pulse sequences, whereas the others use the inflow
phenomena for signal acquisition, such as time-of-flight (TOF) and phase contrast (PC) MRA
techniques.
MRA is more suitable than DSA for a complete evaluation for many vascular diseases. This is
because MRA provides additional information that is relevant to the treatment planning and
prognosis of the disease, such as arterial wall inflammation, mural hematoma, atherosclerotic
plaque composition and morphology, and rupture, in addition to the DSA-like lumenograms. The
true size of an aneurysm can be appreciated more accurately with MR, because it is capable of
demonstrating the mural thrombus and the arterial wall, in addition to the lumen. The three-
dimensional (3D) data set provided by 3D MRA techniques allows multiplanar displays of the
vessels by using postprocessing techniques. Nonrotational DSA, on the other hand, is a 2D
imaging technique that is limited to the acquired views during the procedure. Additionally,
specific MRA techniques can provide functional information that is also relevant to the
determination of the hemodynamic significance of a stenosis such as flow pattern, flow velocity,
and flow volume across the vessel lumen.
MR physics and technical pulse sequence details may seem complex and challenging. One
easy way to learn MR is to first learn how to operate the MR scanner. This provides an
organizational framework based on the decisions needed for patient imaging. The operator
should be able to choose the appropriate pulse sequence as well as the imaging parameters,
such as time to repetition (TR), time to echo (TE), flip angle, field of view (FOV), and k-space
ordering. These are the variables that should be decided according to the region of interest,
(ROI) nature of the vascular disease, and the patient's clinical issues. With this framework, MR
knowledge is more readily acquired, organized and remembered.
This chapter reviews the fundamentals of current MRA techniques, describes effective
utilization for abdominal and peripheral arterial imaging, and addresses technical issues relevant
to endovascular or surgical interventions, as well as stent and graft imaging. Attention is
focused on how to avoid common pitfalls.
MAGNETIC RESONANCE SYSTEM REQUIREMENTS

Three-dimensional contrast-enhanced (CE) MRA is a demanding application requiring short
acquisition times that are essential for dynamic studies to avoid respiratory and extremity
motion artifacts, as well as for high-resolution 3D CE MR angiograms. Developments in
hardware technology have focused mainly on improving gradient systems. Fast gradients are
essential to achieve short echo times and, thereby, short acquisition times (1d). The current
scanners, with a gradient strength of 45 mT/m and slew rate of 200 mT/s, yield TRs of about 3
milliseconds while achieving a typical spatial resolution of 1.5 1.5 1.5 mm3, which, though
far superior in the slice direction, is still inferior to DSA in-plane.
Recently introduced advances in data sampling and reconstruction techniques (e.g., parallel
imaging) improve the spatial resolution and increase the imaging volume while decreasing
acquisition times. Parallel imaging techniques are based on obtaining more than one line of k-
space data per TR using multichannel phased receiver coils. In parallel, not only is the
acquisition faster, but also the center of k-space is compressed into a shorter time, which
reduces motion and ringing artifacts (2, 3, 4, 5, 6, 7, 8, 9, 10). With a given number of phase
encoding steps, the acquisition time can be reduced or the spatial resolution can be increased
by what is referred to as the acceleration factor. The current standard 1.5-T MR systems
typically allow acceleration factors of two- or threefold. All vendors offer parallel imaging
options for their scanners (e.g., sensitivity encoding [SENSE], Phillips Medical Systems; array
spatial
sensitivity encoding technique [ASSET], General Electric Healthcare; generalized
autocalibrating partially parallel acquisition [GRAPPA] [5], Siemens Medical Solutions;
integrated parallel acquisition technique [iPAT], Siemens Medical Solutions; SPEEDER,
Toshiba) that are applicable to most MR imaging methods. With parallel imaging techniques,
only a given number of the data determined by the acceleration factor is acquired, and the
undersampled images must be unfolded. Two techniques and their derivates are used to
reconstruct the undersampled data: Simultaneous acquisition of spatial harmonics (SMASH) (2)
and sensitivity encoding (3,4). Sensitivity encoding uses a prescan to acquire the coil sensitivity
profiles before the actual scan, referred to as the calibration scan. With these profiles, the
aliased image is reconstructed in the image domain. Some newer techniques, such as
GRAPPA, however, provide autocalibration and, thus, do not require running a separate
calibration scan. On a high-field-strength MR system equipped with high-performance
gradients, parallel imaging with an acceleration factor of two or three allows submillimeter
isotropic 3D imaging during a single breath-hold. This technique has also been shown to
decrease venous contamination in the lower stations of runoff examinations (6). The
disadvantage of parallel imaging techniques is the reduction in signal-to-noise ratio (SNR) by a
factor of approximately the square root of the acceleration factor times what is known as a
geometry factor. With 8-channel coils this geometry factor makes acceleration factors >3
impractical, but with 32-channel coils acceleration factors of 5 or 6 become practical. Once the
higher-field-strength magnets are more optimized, SNR loss of parallel imaging may be
overcome with the intrinsic higher SNR of the high-field-strength systems. Alternatively, SNR
can be increased with a higher gadolinium (Gd) dose injected at a faster rate.
TABLE 7-1 PULSE SEQUENCES
Pulse Slice
TR TE FA BW Matrix FOV Other
sequence thickness
Narrow
BW
high SNR
long
At least 4
acquisiti
pixels
Shortest Shortest 512 time; SN
3D 40- 31.25- across the
TR (<5- TE (~1- is
SPGR 45 62.5 transverse
6 ms) 2 msec) 256 inversely
axis of the
related t
vessel
the
square
root of t
BW
Long TR
high
SI, long
acquisiti
time
Short T1
high S
256
2D TOF FC shou
6-7/33 50 15.63 2 18
Foot be on
224
Venc: 15
cm/s for
inflow
256
2D PC Shortest arteries
30 31.25 6 32
Cine PC TE and 100
256
cm/s for
popliteal
arteries
3D PC 256
Venc: 50
of renal TR: 18 30 15.63 3 38
arteries 160 30 cm/s
320 Tempora
3D Shortest 20
35 31.25 1.6 resolutio
TRICKS TE cm
224 of 9-11 s
Tempora
3D 320 resolutio
Shortest
TRICKS, 45 31.25 1.6 40 of 9-11 s
TE
calves 224 coronal
plane
256
Shortest ETL: 16
DIR 45 31.25 8 18
full TE 32
60
MR coils have important effects on the SNR and contrastto-noise ratio (CNR) of the images. All
MR scanners have a body coil built into the wall of the magnet that works as radiofrequency
(rf)-pulse transmitter and receiver. However, the body coil may not be efficient when imaging
small body parts with small vessels, such as calf and foot arteries. As a rule of thumb, the best
coil is the smallest coil that covers the ROI. Circumferential birdcage coils, such as head and
knee coils, tend to have a more homogeneous rf receiver sensitivity, thus they are less likely to
produce artifacts on the images. However, phased array surface coils, such as multichannel
body or peripheral vascular coils can cover a larger imaging volume while providing a high SNR
and CNR compared to the body coil (11).
Automated table motion is preferred for multistation acquisitions. However, even if automated
table motion technology is not available, it is still possible to acquire single-injection multistation
3D CE MRA of the peripheral vessels. This technique involves programming the scanner for
repeated acquisition of the same coronal 3D volume of MRA data, disconnecting the scanner
table from the drive mechanism, and advancing the patient from one station to the next through
the coil by manual table translation. This can also be done using a Teflon sheet placed under
the patient. The patient is physically pulled through the scanner instead of the scanner table
being moved. Using this approach, the mask for background subtraction at the second station
must be obtained after the Gd has cleared.
A continuous table motion technique has recently been introduced to eliminate the time wasted
on table movement, although it is not yet ready for routine clinical use. Some challenges related
to the continuously moving table technique include motion correction artifacts, gradient warp
effects, and the table velocity adjustments required for optimal contrast bolus chasing (12, 13,
14, 15).
Currently 1.5-T MR systems are highly optimized for MRA studies. However, 3-T MR systems
offer a higher SNR compared to 1.5-T MR systems (16,17). Therefore 3-T MR systems are
likely to become the preferred platform for MRA once the technical challenges and artifacts are
addressed. For example, field distortions due to strong attenuation of the rf field as well as
dielectric resonances are of concern at Larmor frequencies
>100 MHz (18). The Larmor frequency is 125 and 64 MHz at 3 and 1.5 T, respectively.
Decreased amplitude and phase distortion of the rf pulse in deep tissues result in MR signal
loss (19). Therefore, rf field inhomogeneity may be a prominent problem with 3-T MR systems.
Another challenge is to avoid exceeding specific absorption rate (SAR) limits. The total rf power
absorbed in the tissues is quantified, referred to as the SAR, and indicated in units of watts per
kilogram. At higher imaging frequencies, rf power is deposited more efficiently in the conducting
tissues, which will be transformed into heat as a result of tissue resistance (20).
PATIENT EVALUATION AND PREPARATION

Patient evaluation prior to scanning is essential for assessing the patient's cooperation level,
determining the most appropriate patient positioning and choice of coil, and avoiding certain
pitfalls. Thorough knowledge of the patient's interventional history (i.e., organ transplantation,
bypass graft, or shunt procedures) and current clinical issues help optimize the MRA
examination. Additionally, metallic materials (i.e., surgical clips, prostheses, stents) cause T2*
susceptibility artifacts and if unrecognized, may lead to misinterpretations as focal stenosis or
occlusion. The type and the location of bypass grafts should be known prior to the MRA
examination. This is particularly important for extra-anatomic bypass grafts, such as
axillofemoral bypass grafts. Because these grafts are very superficial, they can be inadvertently
excluded from the imaging volume if their presence is not known.
For satisfactory image quality, the patients should be informed and reassured about the
procedure before starting the examination. This will help the patient to be more relaxed and
able to hold still during study. Oxygen administration via nasal cannulae and hyperventilation
may help patients with holding their breath for 20 to 30 seconds (21). In patients with severe
chronic obstructive pulmonary disease, the rate of supplemental oxygen should be kept <2 L
per minute. If there is no contraindication, claustrophobic patients may benefit from
premedication with short-acting benzodiazepines, such as diazepam (Valium, 5-10 mg PO [by
mouth]) and lorazepam (Xanax, 1-2 mg PO). In addition to relieving anxiety, premedication will
also help by decreasing the cardiac output, thereby enhancing the image quality.
A 20- or 22-gauge IV catheter is adequate for CE MRA. Right arm access is preferred
because of its direct path to the central circulation. However, if an upper extremity study is
planned, the IV access should be in the contralateral arm. One exception to this rule is MR
venography, in which ipsilateral injection of dilute (20:1) Gd is the best approach.
For abdominal and peripheral MRA, the patient is placed supine on the scanner table, typically
in feet-first position. Head-first position may be preferred for aortic arch, carotid arteries, and
upper extremity MRA studies. Positioning the patient's arms outside of the imaging volume is
preferable to avoid wraparound artifact.
Although not always necessary, setup for respiratory or cardiac monitoring during the initial
patient preparation minimizes scan delays and patient motion after initiation of scanning. The
placement of respiratory bellows is helpful in case of additional respiratory-triggered acquisition
for visceral organs, as well as monitoring of the patient's respiratory status, and compliance
with breath-holding instructions. If flow quantification using PC technique is desired, cardiac
gating should also be set up in advance of the scanning.
When imaging the abdominal aorta and its branches, a torso phased array coil is preferable
due to its high SNR (22,23). If a larger FOV is required, a longer phased array coil with eight or
more channels is more appropriate. If phased array coils are not available, the standard body
coil may be sufficient for 3D CE MRA provided the Gd dose is sufficient to make up for this
coil's inherently lower SNR. Another problem with the body coil is that it is not compatible with
parallel acquisition techniques.
UNENHANCED MAGNETIC RESONANCE ANGIOGRAPHY

TECHNIQUES
The development of the earliest MRA techniques (TOF and PC) was based on flow-related
artifacts on conventional MR pulse sequences (24, 25, 26, 27). These artifacts can be
explained by the amplitude and phase modulations of the MR signal due to washout of
saturated or excited spins and the phase shifts due to the motion of excited spins along
magnetic field gradients.
Time-of-Flight MRA
TOF MRA technique involves sequential acquisition of many thin 2D slices or a thick 3D volume
by using a gradient echo pulse sequence with a short TR, a short TE, and gradient moment
nulling (flow compensation). Two-dimensional techniques use a high flip angle (~60 degrees),
while 3D techniques use a lower or a ramped flip angle. Reformatted images are created by
stacking multiple 2D slices to produce images that are analogous to DSA.
Repetitive rf pulses with a very short TR lead to a gradual decrease in longitudinal
magnetization of the stationary tissues, which is referred to as saturation, because the TR is
too short for complete recovery of the longitudinal magnetization in most stationary tissues. The
magnitude of the residual longitudinal magnetization decreases proportionally to the number of
rf excitations. During TR, some or all of the saturated blood spins within the imaged slice move
out while fresh fully magnetized spins enter into the imaging slice. Since the longitudinal
magnetization of the unsaturated inflowing spins is greater than that of the spins in the
stationary tissues, arteries and veins have a higher signal than the saturated stationary tissues.
The signal intensity of the moving spins is determined by the flow velocity, TR, and slice
thickness. For a high CNR, slices should be prescribed as thin as possible (optimally 1 to 2
mm). Thin slices decrease the chance of in-plane saturation of the moving spins. For 2D TOF,
the slices should be prescribed as perpendicular as possible to the long axis of the vessel
(usually axial) to maximize the inflow effect as well as to reduce artifacts caused by phase
dispersions (dephasing). A long dwell time in the imaging volume may lead to saturation of the
moving spins and signal loss, because they receive too many rf pulses. This is referred to as in-
plane saturation. A sufficiently long TR is also important to allow enough time for fresh
unsaturated spins to enter the imaging slice in between the rf pulses (typically 8 to 10
milliseconds per 1 mm of slice thickness). A flip angle close to 90 degrees can provide better
background saturation. However, a high flip angle is not desired because it results in signal loss
from the moving spins while they travel through the imaging slice. With respect to this trade-off,
it is more appropriate to use a flip angle of 30 to 70 degrees with 2D TOF even if the
background saturation would be less. Lower flip angles reduce pulsatility artifact. Pulsatility
artifact can also be reduced with electrocardiographic (ECG) gating, but at the expense of
increasing scan time.
The SNR of TOF also depends on the flow velocity; the faster the flow velocity, the higher the
signal intensity. Because spins with slow flow receive more rf pulses during single slice
acquisition, these spins become saturated and produce less signal. The difference between the
longitudinal magnetization of moving spins and the stationary tissues decreases as flow
becomes slower, leading to a low vessel/background contrast.
Although the shorter the TR the greater the background saturation, when using a very short TR,
the risk of the saturation of the moving spins increases as well due to the greater number of rf
pulses received during acquisition. Therefore, TR should be adjusted according to patient-
specific factors. For example, while a shorter TR provides a better CNR in patients with fast
flow or high cardiac output, it would result in a low CNR in patients with slow flow or low
cardiac output, or in vessel segments with slow flow such as aneurysmal arteries, pedal
arteries, and veins.
The flow velocity is slower close to the vessel wall than the vessel center due to the laminar
flow in the arteries. Cross-sectional flow velocity differences are represented as phase shifts in
k-space and signal intensity magnitude on the final images. The cross-sectional area of a
peripheral artery can be as small as a few pixels and the single pixel may include a wide
spectrum of phase dispersions due to the velocity differences. Vector cancellation of phase
shifts in different directions may lead to very low or near-zero transverse magnetization.
Therefore the signal in poststenotic vessel segments or in aneurysms can be zero or very low.
Thinner slices as well as shorter TE may help to reduce this spin dephasing artifact.
The flow velocity is different at different time points of the cardiac cycle: Fastest during systole
and slowest during diastole. Intrapixel phase dispersions are enhanced by this pulsatile flow
and may lead to ghosting artifacts if ECG gating is not employed. Gradient moment nulling
(flow compensation) may also correct the intrapixel phase dispersions, thereby reducing
ghosting artifacts.
In addition to the TR of the pulse sequence, the degree of background saturation depends on
the T1 of the tissues. Saturation is more effective in tissues with a long T1 than those with a
short T1. For example, fat tissue has a very short T1, thus its longitudinal magnetization
recovers faster than tissues with a longer T1, such as fluid. Therefore the residual longitudinal
magnetization from the fat tissues can interfere with the image quality by causing high signal.
Magnetization transfer pulses may help reduce protein-rich background signal such as in the
brain or other organs. For 3D TOF acquisition phase encoding is added in the slice-select
direction. This allows the slab to be partitioned into slices. The advantage of 3D TOF over the
2D acquisition is the ability to acquire isotropic voxels smaller than 1 mm3, thereby providing
higher spatial resolution with a reasonable SNR. This MRA technique is usually preferred to
using image vessels that are very small in caliber such as the circle of Willis. Since 3D TOF
MRA requires a longer acquisition time compared to 2D TOF MRA for the same imaging
volume, its applications are usually limited to the head and neck vessels. The disadvantage of
this technique is the gradual saturation of the blood while traveling through a large volume,
thereby resulting in gradual signal reduction toward the distal edge of the 3D volume. This
effect is more prominent on slow-moving spins. For example, slow-moving spins close to the
vessel wall may become saturated and lead to underestimation of the vessel diameter. To avoid
this shortcoming, the flip angle is lowered between 15 and 20 degrees, and ideally a ramped
excitation is utilized with a lower flip angle where arterial spins enter the slab and a higher flip
angle at the other edge of the 3D slab to capture more signal before the spins exit the imaging
volume.
The presaturation band is a 90-degree rf pulse that saturates the spins entering the imaging
area. This band is typically placed adjacent to the imaging area to saturate the undesired inflow
signal from the veins. TOF MRA techniques do not require MR contrast agents, although the T1
shortening effect of contrast agents may help to improve the SNR and vascular delineation.
Although TOF can be robust in certain clinical situations, the technique has several important
limitations (28). First, TOF is usually limited to the axial plane, to stay perpendicular to the
vessels. For a high CNR, the slices should be as thin as possible; in other words, complete
evaluation of the lower extremity arteries from the infrarenal abdominal aorta through the foot
may take hours and requires reviewing hundreds of slices. Second, TOF MRA is very sensitive
to motion, including respiratory and pulsation artifacts, which are unavoidable for long
acquisition times. Third, in-plane spin saturation may severely degrade image quality in tortuous
and ectatic or aneurysmal vessels, which are common with atherosclerotic disease of the aorta
and the pelvic vessels. Besides, the vessels reentering into the imaging plane, such as tortuous,
naturally curved, or collateral vessels, may not be visible because the presaturation band
applied for saturating moving spins in the veins also saturates arterial spins that reenter the
imaging plane from the opposite direction (Fig. 7-1). Fourth, turbulent or accelerated flow in the
segments just distal to a stenosis may suffer from signal loss due to spin dephasing. This may
cause an overestimation of the length and degree of stenosis (29). Turbulent or slow flow in
aneurysmal vessel segments, however, may lead to underestimation of the vessel diameter as
well. Fifth, methemoglobin in fresh thrombus has a very short T1, and thus, it may resemble
flow signal on TOF MRA images and lead to misdiagnosis. Finally, gradient echo pulse
sequences, such as TOF, are very sensitive to magnetic susceptibility artifacts. Distortion of the
magnetic field due to metallic clips, stents, coils, and neighboring prosthesis may lead to total
signal loss from the vessel segment simulating an occlusion.
Phase Contrast Magnetic Resonance Angiography

When using TOF technique, the phase shifts in the transverse magnetization of the moving
spins lead to various undesired flow artifacts. PC MRA exploits these phase shifts to quantify
blood flow. In this technique, the transverse magnetization of moving spins is modulated by
applying an additional bipolar flow encoding gradient to a TOF sequence. The bipolar gradient
introduces phase shifts to the transverse magnetizations of only moving spins. Stationary spins
are not affected. The relationship between the phase shift and the flow velocity is linear; in
other words, the phase shift increases proportionally to the velocity of moving spin (30).
The most important operator-defined parameter of this MRA technique is the velocity encoding
variable (Venc), which reflects the estimated peak flow velocity in the vessel of interest. Once
the Venc is set (by the operator), the scanner calculates the amplitude and duration of the
bipolar gradient to provide a 180-degree phase shift to those spins with peak velocity. Signal
intensity is proportional to spin velocity. PC is also flow direction sensitive; spins flowing in the
opposite direction do not provide signal. Therefore, the bipolar gradient should be applied in the
direction of the flow. One pitfall is that velocities higher than the set value of Venc are depicted
as spins flowing in reverse direction due to the phase wrap. This is also referred as to aliasing.
Another pitfall is setting the Venc too high; in this case, the sensitivity to slow flow decreases.
This may underestimate the cross-sectional area of the vessel due to the laminar flow pattern in
the arteries, in which the flow velocity is slower close to the vessel wall compared with the
center of the vessel. In most patients, a Venc of 75 cm per second is appropriate for
renal artery evaluation, but in the case of chronic heart failure or other low-cardiac-output
conditions, a lower Venc should be considered.
FIGURE 7-1. (A) Sagittal projection of unenhanced 2D TOF and (B) Gd-enhanced 3D
TRICKS of the left foot on the sagittal plane. The anterior tibial artery is severely diseased
distally and the dorsalis pedis artery is occluded at its origin. However, the dorsalis pedis is
reconstituted in its mid segment via a collateral vessel (open arrow) from the anterior tibial
artery. Note that retrograde flow in the collateral vessel (black arrow) is not visible on the
2D TOF image due to the venous saturation band, whereas it is visualized on 3D CE MRA.
Additionally, the plantar arch is not seen on the 2D TOF image because of the in-plane
saturation, while in-plane saturation does not cause signal loss on 3D MRA (white arrow).
Note that for 3D PC MRA, which typically creates a speed image where there is no aliasing,
the Venc should be set to the mean velocity instead of the peak velocity. For 3D PC speed
images of the renal arteries a Venc of 30 to 50 cm per second is more appropriate.
Two-dimensional PC can be used for flow measurement across a vessel segment. This is
typically synchronized to the cardiac cycle and known as cine PC. Cine PC measurements yield
quantitative flow parameters, such as mean flow velocity, maximum flow velocity, mean
temporal flow, and time to peak velocity. In addition, a Dopplerlike flow profile can be
performed to evaluate the blood flow qualitatively. When used for this purpose, a thin single
imaging slice is set up perpendicular to the long axis of the artery. The imaging slice must not
be positioned in a stenosis but, rather, 1 cm distally. Otherwise, turbulent flow may lead to false
results due to aliasing or intravoxel dephasing.
Cine PC acquisition of arteries requires ECG gating to obtain images through a complete
cardiac cycle. A temporal resolution of about 30 milliseconds is ideal for complete and correct
tracking of the pulse wave. Although the acquisition time depends on the heart rate of the
patient, it may be 1 to 2 minutes using a matrix of 256 256. On the final images, the vessel
lumen is seen as a gray color spectrum from bright signal through no signal, depending on the
velocity and the direction of the flow; stationary tissues appear gray. Flow velocities in each
pixel of the cross-sectional area of a vessel lumen are used for constructing velocity maps; this
map is used for calculating flow volume. The negative and positive phase shifts are plotted and
used for quantification of the amount of forward and backward flow across the vessel lumen
during each cardiac cycle (31) (Fig. 7-2).
Three-dimensional PC MRA acquisition provides speed images analogous to DSA images, with
a high spatial resolution and SNR. Since the vessels are not straight in most body parts, the
technique's intrinsic sensitivity to flow direction should be eliminated. To do so, flow-sensitive
gradients are applied in all three axes: The slice-select, phase encoding, and frequency
encoding directions. Then the phase shifts in each voxel are used to calculate the vector
magnitude of the flow velocity. On 3D PC images, moving spins appear bright in contrast to
stationary spins. This technique has two important drawbacks: First, it is more time-consuming
compared to 2D, because the bipolar gradients should be applied in all three orthogonal planes;
and second, the wide spectrum phase shifts in a voxel may result in
complete signal loss due to the cancellation of transverse magnetizations in different directions,
leading to underestimation of the vessel diameter. Nevertheless, this feature of 3D PC MRA can
be exploited for determining the hemodynamic significance of the occlusive disease. On 3D PC
MR angiograms, signal loss reflects the loss of phase coherence due to the acceleration of the
flow velocity and the turbulent flow in the poststenotic vessel segment, which is consistent with
a proximal narrowing of the cross-sectional area of >70% (32,33) (Fig. 7-3). On the other
hand, mild stenoses also lead to acceleration of the flow velocity through the stenotic segment.
However, just opposite to the flow jet occurring in the poststenotic segment that is distal to
severe stenosis, mild stenosis causes an acceleration of the laminar flow, which results in
brighter signal intensity with blooming artifact causing one to overlook the stenosis.
FIGURE 7-2. White lines on the coronal image indicate sites of cine PC flow
measurements above and below both superficial femoral arteries (SFAs). A: On the right
side, there is a long segment occlusion of the superficial femoral artery and above-the-
knee segment of the popliteal artery. The flow pattern above the occluded segment shows
a biphasic pattern, with a lower peak systolic amplitude, possibly due to the proximal inflow
disease. The flow velocity curve below the occluded segment, however, demonstrates loss
of the normal triphasic pattern of normal peripheral flow, and a flow velocity close to zero.
B: On the left side, SFA demonstrates multiple mild stenoses in its course. The flow
pattern in the proximal SFA shows a normal triphasic flow pattern. However, in the popliteal
artery below the diseased segment, peak systolic flow is delayed and the amplitude of
peak systolic velocity is lower compared to the normal proximal SFA segment. Note that
the triphasic flow pattern is preserved, because the disease in the left is hemodynamically
insignificant. (Reprinted with permission from Mohajer K, Zhang H, Gurell D, et al.
Superficial femoral artery occlusive disease severity correlates with MR cine phase-
contrast flow measurements. J Magn Reson Imaging. 2006;23:355-360.)
Steady-State Free Precession Imaging

The signal intensity in steady-state free precession (SSFP) acquisition relies on the T2-to-T1
ratio and is generally less flow dependent (22,34). This pulse sequence is known as True-FISP
(Siemens Medical Solutions, Erlangen, Germany), FIESTA (General Electric Healthcare,
Waukesha, WI, USA), and balanced FFE (Philips Medical Systems, Best, The Netherlands).
SSFP can be used as an alternative MRA technique in patients without adequate venous
access, or when there is a contraindication for paramagnetic contrast agents. SSFP bright
blood technique can be useful in detecting a thrombus or an intimal tear. Fast breath-hold 3D
SSFP MRA has been shown to be feasible for evaluating the renal arteries (35). Although the
vascular signal on SSFP images is not related to the T1 shortening effect of paramagnetic
contrast agents, vascular signal improves on postcontrast acquisitions (36).
FIGURE 7-3. A: Axial reformatted MIP image of 3D CE MRA shows a severe stenosis
(arrow) in the proximal segment of the left renal artery. B: On projection image from 3D
PC flow MRA, note the signal loss in the left renal artery due to the dephasing. This finding
is consistent with the hemodynamically significant stenosis and associated poststenotic
flow jet and turbulence.
The drawback of this pulse sequence is high sensitivity to B0 inhomogeneities, for example,
metallic susceptibility artifacts from stents or clips.
DIMENSIONAL CONTRAST-ENHANCED MRA

Among all of the MRA techniques, 3D CE MRA is the most versatile, effective, and accurate. It
can be applied successfully to nearly all vascular territories. Comparative studies using DSA
reveal a sensitivity of >92% and specificity of >91% for detecting and grading atherosclerotic
disease of the abdominal aorta, its vessel branches, and peripheral arteries of lower
extremities (11,23,37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54).
Three-dimensional acquisition yields the highest possible spatial resolution, improves
background suppression, and requires significantly shorter acquisition times.
The vessel signal in 3D CE MRA relies on the T1 shortening effect of the contrast agent rather
than on flow-related changes in spin magnetization (22,23,37,55,56). Therefore, compared to
TOF and PC techniques, 3D CE MRA is less sensitive to in-plane saturation and flow-related
artifacts (23,28,29,37, 38, 39, 40). This allows flexibility to set the imaging volume in any
desired plane with the minimum number of slices for imaging the longest possible vessel
segment with the shortest acquisition time. Also, 3D CE MRA is less vulnerable to magnetic
susceptibility artifacts compared with TOF (23,28,37,42,56).
Pulse Sequence Parameters

Three-dimensional CE MRA is performed by using a 3D spoiled gradient echo pulse sequence
during the arterial, venous, and delayed phases of a Gd contrast bolus. Gd chelates transiently
shorten the blood T1 below the T1 of the background tissues, thereby allowing direct
visualization of blood on T1-weighted sequences. The T1 contrast is accentuated by spoiling of
the residual transverse magnetization. Spoiling increases contrast by suppressing background
tissue signal.
Pulse sequence parameters, bolus timing, bolus dose, and injection rate should be adjusted
based on the ROI, as well as individual differences such as cardiac output and intravenous
location. The acquisition time is determined by TR number of phase encode steps number
of slices fraction of k-space sampled/acceleration factor. These parameters can be adjusted
to achieve the optimal anatomic coverage and scan time.
Signal intensity is maximized when TR is long or T1 is short. However, faster acquisition
requires a short TR, and thus the T1 should be shortened as much as possible with Gd chelate
administration.
The receiver bandwidth also impacts the TR. Increasing the receiver bandwidth reduces the TR
and TE but at the expense of the SNR. The loss in SNR can be balanced somewhat by
increasing the Gd dose and injection rate, thereby increasing the Gd concentration in the ROI
during central k-space sampling.
The TE and TR are determined by the magnetic field and gradient strength. In general, the
shortest possible TR (<5 milliseconds) and TE (<3 milliseconds) are essential for keeping the
scan time short. The other modifications in pulse sequence parameters for shortening the
acquisition time include partial Fourier (e.g., 0.5 NEX), partial phase FOV, and parallel imaging
techniques. Parallel imaging is a recently introduced option that increases the acquisition speed
by a factor of two or three (3,4). When employing parallel imaging technique, however, a full
phase FOV should be used to avoid uncorrectable reconstruction artifacts. Nevertheless, any
decrease in scan time always leads to some reduction in SNR.
Acquisition times can be shortened by decreasing the spatial resolution or reducing the volume
of coverage. For accurate assessment of a stenosis, however, cross-sectional area requires at
least four pixels. However, achieving an isometric voxel size is very difficult, because the in-
plane resolution is often higher than in the slice-select direction. Therefore, MR angiograms
may not be of equal quality for vessels in different orientations. Using a smaller FOV improves
the spatial resolution with an identical phase and frequency matrix. However, this method can
only be applied for small vascular territories, such as renal arteries.
Besides, while the voxel size decreases, the spatial resolution improves at the expense of the
SNR. However, adjusting other pulse sequence parameters to obtain a higher SNR will result in
an increased scan time.
Thinner slices will produce a higher spatial resolution but require more time if more slices are
necessary to cover the anatomy. A short TR allows a higher temporal resolution that is directly
correlated with the acquisition time.
A short TE (<3 milliseconds) is essential to minimize signal loss caused by spin dephasing due
to turbulent flow or a poststenotic flow jet. A short TE also decreases T2* metallic susceptibility
artifacts caused by surgical clips, stents, or calcifications (57, 58, 59). Increasing the
bandwidth may help to achieve a shorter TE but, again, at the expense of the SNR. The flip
angle can be in the range of 15 to 45 degrees. However, in the case of a vascular stent, a
higher flip angle (60 to 75 degrees) may provide better visualization of the stent lumen by
overcoming the Faraday cage rf shielding effect. With 3-T systems, SAR limitations will
determine the flip angle, which should be as high as possible without increasing the TR.
Image Features and k-Space Ordering

The image contrast is mostly determined by the central k-space data (low spatial frequencies).
The peripheral k-space data (high spatial frequencies), however, dominate the visualization of
fine details. Thus, adequate bolus timing with respect to central k-space data acquisition is
crucial. The 3D Gd MRA acquisition time is usually longer than the injection duration. However,
sustaining the contrast injection over the entire scan time is not required. Synchronization of the
k-space center acquisition with the short-duration contrast peak in the artery can be achieved
using different techniques.
In linear (sequential) view ordering technique, the central k-space data are acquired during the
middle of the scan, whereas in centric (60)/elliptical centric (61) view ordering schemes, the
central k-space data are collected at the beginning of the scan. The advantage of linear
ordering over the centric/elliptical centric ordering is the decreased sensitivity to timing errors
(62). Elliptical centric view ordering, however, is a better strategy when fluoroscopic or
navigator triggering is employed to synchronize the bolus arterial phase with the center of the k-
space (61). Additionally, the contrast on an MR angiogram that has been acquired with elliptical
centric view ordering is arterial only, because venous enhancement occurs during the peripheral
k-space readout. Therefore, elliptical centric view ordering (and especially recessed elliptical
centric ordering) provides better venous suppression compared to sequential acquisition (63).
Gadolinium Dose and Injection Rate for Three-Dimensional

Contrast-Enhanced Magnetic Resonance Angiography
A short scan time reduces signal averaging and thus reduces the overall image SNR. However,
this setback can be offset by injecting a high dose of Gd chelate at a high rate. This provides a
high Gd concentration, thus a high SNR and CNR, in the arteries. The T1 shortening effect of
Gd chelate at 1.5 T can be estimated as follows (37):
1/T1 = 1/1200 + (R1 [Gd])
where T1 is the longitudinal relaxation time of Gd-containing blood, R1 is the T1 relaxivity of the
Gd chelate, and [Gd] is the Gd concentration in the vessel of interest. The T1 of the blood
(without contrast agent) is 1,200 milliseconds. Most currently available Gd chelates have
almost-equal relaxivities. Therefore, for dynamic studies, the blood T1 shortening effect of Gd
chelates is mostly related to the contrast infusion rate and circulation time (cardiac output)
rather than the contrast dose. When the injection rate is doubled, the [Gd] in the vessel
doubles, and as a result, T1 relaxation of the blood decreases to half, with a proportional
increase in SNR. However, there is a reverse correlation between the [Gd] and the cardiac
output (liters per minute). For good arterial timing, therefore, the injection rate should be
adjusted according to the variables affecting the contrast travel speed, such as patient's age
and cardiac output.
Although in theory faster injections yield a better SNR, an injection rate of 2 to 3 mL per second
typically provides the best results in most arterial territories. Higher injection rates do not
provide a significant improvement in SNR or T1 shortening effect in patients with normal cardiac
output (64). Slower injection rates, however, can be used with bolus chase peripheral MRA
techniques for prolonged arterial phase in extended vascular territories (65,66). In general, 0.2
mmol/kg (30 to 40 mL) of extracellular Gd-based contrast agent provides adequate arterial
signal when injected at a rate of 2 mL per second (64,67) and synchronization with the k-space
center is optimal.
To image venous anatomy, a higher contrast dose or extension of the bolus duration by
administering the contrast agent at biphasic rates (the first half of the contrast dose is
administered at a rate of 2 mL per second, and the remaining dose administered at a dose of
1.5 mL per second) is recommended. Following contrast administration, the distal edge of the
bolus should be flushed with 20 to 30 mL of saline to advance the entire bolus into the central
circulation (68).
Bolus Timing
Adequate synchronization of the contrast transit through the vessel of interest is the most
essential part of 3D CE MRA (22,56). The first attempts at acquiring arteriograms included
infusion of the contrast agent at a slow rate through the entire acquisition, for 3 to 4 minutes
(37,55). The introduction of a fast 3D spoiled gradient echo pulse sequence has revolutionized
3D CE MRA by enabling breath-hold acquisitions, albeit while making bolus timing issues more
complicated. The simplest bolus timing technique is the best guess method, in which the
operator estimates the contrast travel time from the site of injection to the area of interest.
Transit times from the antecubital injection site to the abdominal aorta, however, are quite
variable (range, 10 to 60 seconds) in each patient and depend on the patient's age, cardiac
output, and vascular pathologies between the injection site and the ROI, such as an aortic
aneurysm (69,70). Therefore, the so-called best guess method has been retired in most
applications of 3D CE MRA.
The test bolus method includes real-time scanning of the ROI (for the abdominal aorta, this is
usually the midaorta) using a fast T1-weighted 2D spoiled gradient echo sequence. A single
thick slice is scanned every 1 to 2 seconds following a 2-mL Gd-chelate bolus and a 20-mL
saline flush for 40 to 60 seconds. The test bolus saline injection rate as well as the amount of
saline flush should be the same as planned for the actual acquisition (22,70,71). For the test
bolus imaging slice it is useful to set a superior flow saturation band or a blood nulling inversion
pulse to avoid TOF effects. Peak arterial enhancement time is determined using the ROI tool of
the scanner software. While calculating the scan delay time for the actual 3D MRA acquisition,
an extra 5 seconds should be added to the contrast arrival time. This is because the time to
arterial peak (rise time) is longer for a high contrast dose than for a low test dose. Soft tissue
or venous enhancement is usually not an issue in 3D CE MRA, because a background
subtraction will be applied to the postcontrast images. However, Gd chelate within either the
renal collecting system or the renal veins may superimpose on the arterial structures when
imaging the aorta or its branches. Variations in the hemodynamic status of the patient can also
affect the contrast arrival time, thereby making the test bolus an unreliable reference for the
actual 3D CE MRA bolus timing.
Synchronization of the central k-space encoding with the contrast concentration peak in the
artery of interest can also be accomplished using automated software, such as SmartPrep
(General Electric Healthcare) (60,72,73), or semiautomated MR fluoroscopy (e.g., CareBolus,
Siemens Medical Solutions; BolusTrak, Phillips Medical Systems; FluoroTrigger, General
Electric Healthcare) (74,75). These techniques are used during actual contrast bolus injection.
For automated bolus detection, a navigator is placed in the artery of interest (typically at the
level of the renal arteries for abdominal MRA), and then the navigator volume is scanned
repeatedly. As soon as the contrast arrival is detected (an increase in signal of >20% and 2
standard deviations over the operator-determined threshold), an elliptical centric 3D MRA
acquisition is initiated after a scan delay of 5 seconds (72). Scan delay is required for patient
breath-holding.
MR fluoroscopy is a semiautomated timing technique, including two phases: First, the
monitoring phase and, second, the 3D CE MRA acquisition phase. Contrast arrival is monitored
with a fast 2D gradient echo MRA sequence that produces one or two images per second. This
technique allows the operator to watch for the contrast arrival in the ROI; the operator then
manually starts the 3D acquisition at or near the center of k-space (74,75). Fluoroscopic
imaging is particularly advantageous if there is an aortic aneurysm, because blood flow in an
aneurysmal segment tends to be very slow. For example, in the case of an abdominal aortic
aneurysm, triggering of the actual acquisition should be delayed until there is complete filling of
the aneurysmal segment to avoid ringing artifact in the distal arterial segments.
Three-Dimensional Time-Resolved Imaging of Contrast

Kinetics Magnetic Resonance Angiography
Three-dimensional time-resolved imaging of contrast kinetics (3D TRICKS) is a refinement of
keyhole imaging in which the center of the k-space is sampled more frequently than the
periphery of the k-space. Relative oversampling of the
central k-space allows more updates of the contrast information compared to the detail
information, thereby yielding a time-resolved dynamic series of 3D CE MRA without significant
compromise in spatial resolution (7,8,10,76, 77, 78). The 3D TRICKS MRA technique has been
shown to improve vessel depiction due to the decreased venous overlay of the major blood
vessels of the abdomen, thigh, and calf compared to single-injection bolus chase MRA (11,79).
Nevertheless, the spatial resolution of time-resolved MRA techniques is relatively low compared
with that of conventional 3D CE MRA. The voxel size of dynamic studies is usually twice the
voxel size of conventional 3D CE MRA, as a trade-off for temporal resolution.
When using TRICKS, the scanner acquires a mask scan for automatic subtraction of
background signal from the postcontrast images. Then the same 3D volume is repeatedly
scanned using a 3D gradient echo sequence (TRICKS) during and after rapid 10- to 12-mL Gd
bolus injection at a rate of 2.5 mL per second with a 20-mL saline flush at the same injection
rate.
For foot and calf MRA, a temporal resolution of 8 to 9 seconds is usually adequate to acquire
both arterial and venous phases. This allows prescribing thinner slices with a high spatial
resolution. However, when using this technique for vascular territories requiring breath-hold,
such as thoracic or abdominal vessels, scan time is limited by breath-hold. The spatial
resolution should be decreased by increasing the slice thickness and/or reducing the volume of
coverage. The other important drawback of this technique is the long processing time
necessary to create and analyze an enormous number of images from numerous 3D datasets.
MAGNETIC RESONANCE ANGIOGRAPHY OF THE

ABDOMINAL AORTA AND ITS BRANCHES
There are numerous pulse sequences available for evaluating the diverse pathology that affects
the aorta and its visceral branches. Preliminary imaging using precontrast and T1-weighted
black blood sequences as well as postcontrast SSFP images or SPGR images with fat
saturation is useful to assess the morphology of the aorta and adjacent structures and allow a
better appreciation of the areas showing contrast enhancement. A T1-weighted spin echo pulse
sequence may be preferred as the initial sequence in any vascular territory. The blood flow
between the 90- and the 180-degree rf pulses creates a signal void due to echo dephasing,
thereby showing the vascular anatomy with a black blood effect. This black blood effect can
be more effectively produced using the double inversion recovery technique with ECG gating
and breath-holding when scanning the thoracic aorta. A singe-shot fast spin echo (SSFSE or
HASTE) pulse sequence may also be acceptable, especially in the abdominal aorta. A double-
inversion recovery fast spin echo pulse sequence provides morphologic information about the
vessel wall and adjacent structures and, thus, has became standard for evaluating most
abdominal aortic pathologies, such as inflammatory aneurysms of the aorta, intramural
hematoma, and mural thrombus.
Flow-based unenhanced MRA techniques are usually suboptimal for comprehensive imaging of
the abdominal vessels, because flow velocities are variable in different vessels, and blood flow
is multidirectional. Therefore, 3D CE MRA using a spoiled gradient echo pulse sequence is the
mainstay in the investigative approach to evaluation of abdominal vascular pathologies and
angiographic illustration of the abdominal vasculature.
Three-dimensional CE MRA of the abdominal aorta typically is performed using a coronal or
oblique coronal prescription, because coronal volume orientation yields the smallest possible
FOV with the highest possible spatial resolution to include pelvic vessels in addition to the
abdominal aorta in the same slab. This reduction in the FOV improves the spatial resolution. An
axial acquisition may enable a smaller anterior-posterior dimension, thereby further reducing the
scan time. However, axial prescriptions would limit the cranial-caudal coverage.
Current 1.5-T MR scanners allow 3D MRA acquisition with spatial resolution adequate for
diagnostic visualization of the abdominal aorta and its branch vessel origins during a 20- to 30-
second breath-hold. Attempts at faster scanning yield a slightly reduced spatial resolution and
therefore are reserved for patients with shortness of breath. An initial precontrast 3D data set
with the same imaging parameters as the actual 3D MRA acquisition is performed for both
mask subtraction and ensuring proper placement of the imaging volume. This acquisition is
followed by postcontrast dynamic 3D MRA data acquisition in at least three phases (arterial,
arteriovenous, and delayed). The arteriovenous (portal) phase usually begins 30 to 40 seconds
after the arterial contrast peak. This phase is usually sufficient for evaluating venous structures,
arterial dissections, parenchymal enhancement patterns, and tumors (Figs. 7-4 and 7-5).
Delayed phase imaging is particularly useful for demonstrating parenchymal organ
enhancement and enhancement in vessels with slow flow, such as abdominal aorta aneurysm
(AAA), false lumen of the aortic dissection, collateral vessels, and vessel segments distal to
diffuse or high-grade stenoses. A more delayed phase may be acquired just for renal collecting
systems. Renal excretion of Gd chelates can be judged at 10 minutes and is substantially
improved by intravenous injection of 10 mg of lasix immediately following the Gd bolus.
MAGNETIC RESONANCE ANGIOGRAPHY

Peripheral 3D CE MRA study can be done using different methods, such as multi-injection,
multistation, and single-injection multistation (bolus chase) (37,60,65,66,80, 81, 82, 83, 84, 85,
86). The hybrid method includes stationary time-resolved examination of the foot and calves
and a two-station runoff in the abdomen and thighs (11,54). Single-injection multistation bolus
chase MRA improves the speed, eliminates motion artifacts due to patient repositioning, and
simplifies bolus timing (65). However, because of differences in MR platforms, there is no
standard peripheral 3D CE MRA technique.
Our preference is to begin the comprehensive peripheral MRA protocol with precontrast high-
resolution 2D TOF and time-resolved Gd MRA of the symptomatic foot. This is followed by
coronal time-resolved MRA of the calves following the second IV contrast administration and
two- or three-station 3D bolus chase MRA covering the region from the infrarenal aorta to the
ankles following the third IV contrast administration (Fig. 7-6).
Time-Resolved Contrast-Enhanced Magnetic Resonance

Angiography of the Foot and Calves
Time-resolved MRA of the foot is usually performed using a head or extremity coil. The ideal
imaging plane for feet is the sagittal plane (Fig. 7-7). In general, only the symptomatic side is
imaged, with a narrow sagittal slab with a high resolution. If needed, both feet can be imaged
on the same scan. However, a wider sagittal volume with a greater number and thickness of
slices is required to cover both feet, at the expense of both temporal and spatial resolution. For
the calves, a long phased array coil is more appropriate, and the coronal plane is preferred to
cover both sides (Fig. 7-8).
FIGURE 7-4. A 71-year-old man with worsening leg edema and uteretal stenting for right
hydronephrosis. A: The arterial phase of 3D CE MRA demonstrates atherosclerotic wall
irregularities in the infrarenal aorta and both common iliac arteries. The right kidney (*) is
smaller than the left kidney, and the right renal artery is small in caliber (arrow). B:
Subvolume MIP image of venous phase 3D CE MRA shows the enhancing soft tissue mass
around the right renal artery, right renal pelvis, and para-aortic area (curved arrows). C:
Postcontrast 3D fat suppressed T1-weighted axial image demonstrating a retroperitoneal
mass (biopsy: retroperitoneal fibrosis) encasing the right ureter and inferior vena cava
(open arrow).
FIGURE 7-5. A 75-year-old woman with bilateral leg swelling after knee replacement was
referred for evaluation of the inferior vena cava and deep pelvic veins. A: The venous
phase of 3D CE MRA demonstrates an enhancing pericaval mass (arrow). B: Subvolume
coronal MIP image shows that the mass is originating from the wall of the inferior vena
cava and extending into the lumen (open arrow). Diagnosis: leiomyosarcoma of inferior
vena cava.
FIGURE 7-6. Multi-injection multistation 3D MRA of lower extremities. Widely patent inflow,
outflow, and runoff arteries. Note the arteriovenous malformation in the right calf fed by the
peroneal artery (arrow).
Three-Dimensional Contrast-Enhanced Magnetic Resonance

Angriography of the Abdomen and Legs
The arms can be aligned next to the body for peripheral MRA studies to keep the patient
comfortable. The first (abdomenpelvis) station is usually set up with the largest FOV on the
coronal plane to cover the pelvic vessels. If the parallel imaging technique is preferred for the
first station, the arms should be extended over the patient's head or crossed on the chest to
avoid wraparound artifact, which may severely degrade the image quality.
To minimize motion artifacts, it is useful to tape the feet together and pack them in foam.
Finally, two MR-compatible blood pressure cuffs or tourniquets are needed for applying
subsystolic compression to the thighs, which will prevent venous contamination in the calf
station. The cuffs are placed on the thighs as cranially as possible (near the groin) for optimal
venous compression and are not inflated until just before mask imaging. Inflating the cuffs prior
to mask image acquisition, however, is important to avoid position-changing of the thighs due to
the inflated cuffs in between mask and CE acquisitions. An inflation pressure of 60 mm Hg
during the scan is usually adequate for preventing venous contamination in distal areas. In
patients with a femoral-popliteal graft, a pressure of 40 mm Hg is advised due to the theoretical
risk of thrombosis of the graft lumen from compression.
For the first-station 3D CE MRA, it is best to use the sequential k-space view order to avoid
ringing artifacts. For the second and third stations, elliptical centric view k-space ordering is
preferred for better venous suppression.
The typical total Gd dose for the entire bolus chase 3D Gd MRA study is 0.3 mmol/kg. A fixed
dose of 45 mL of Gd can be used in all patients to simplify injection and bolus timing.
Exceptions can be made for patients weighing <50 kg (30 mL) and >100 kg (60 mL).
A fast injection rate will shorten the T1 relaxation time much more than a slower injection rate.
However, a slower, longer injection rate can produce a more uniform T1 throughout the entire
bolus chase, thereby inducing fewer artifacts. The infusion rate should be fast enough to obtain
sufficient arterial enhancement at the three successive stations but slow enough to allow a long
bolus to completely fill the collaterals without venous enhancement. The preferred injection
duration is approximately 50% to 60% of the acquisition time. In general, the optimal injection
rate for peripheral vascular studies is 1.5 to 2 mL per second in most cases. The contrast bolus
is immediately followed by a 20- to 30-mL saline flush at the same injection rate, to push the
bolus through the superior vena cava. A split dose is thought to be useful when the scan time is
too long for proper sharing of the bolus between stations. Some investigators have advocated a
split-dose regimen with an initial high injection rate of ~2 mL per second for the first 20 mL of
Gd, followed by a lower rate of ~0.5 to 1 mL per second for the remaining Gd and the saline
flush.
Achieving good bolus timing for multistation lower extremity examinations is more challenging
than for single-station examinations. The acquisition of the first (abdomen-pelvis)
station must be fast enough to prevent venous contamination in the distal stations without too
much compromise in spatial resolution. This can be managed by using previously described fast
acquisition strategies, including parallel imaging. Alternative methods to keep up with the bolus
travel and to decrease venous contamination in the distal stations include midthigh venous
compression and continuously moving table acquisitions (6,14,87). Nevertheless, bolus timing
can still be very difficult for distal stations, owing to variability in the flow rates and Gd travel
times in the legs (79,88).
FIGURE 7-7. A: 3D TRICKS MRA of the left foot in the sagittal plane demonstrates widely
patent pedal arteries. B: 3D TRICKS MRA of the left foot in another patient shows that the
distal segment of the anterior tibial artery is small in caliber and the dorsalis pedis is
occluded in its mid segment (arrow). The pedal arch is reconstituted via the lateral plantar
branch of the posterior tibial artery (open arrow).
FIGURE 7-8. Three-dimensional time-resolved MRA of calves in the coronal plane.
Temporal resolution is 1 image per 9 seconds. Right runoff: Popliteal artery is widely
patent. Anterior tibial artery and tibioperoneal trunk are occluded. Posterior tibial and
peroneal arteries reconstitute via the collaterals from the sural artery and other muscular
branches. Left runoff: Mild to moderate focal stenosis of the popliteal artery at its below-
knee segment. Anterior and posterior tibial arteries are occluded proximally. There is
single-vessel runoff via the widely patent peroneal artery. Note the retrograde filling of the
posterior tibial artery from the peroneal artery via the communicating branch (arrows).
Time-resolved MRA of the foot or the calf vessels can provide valuable bolus arrival time
information that will be used for bolus timing for each station, as well as arteriovenous transition
times. For average individuals, injected from the
antecubital vein, the contrast arrival time in the common femoral artery is 24 6 seconds, with
an additional 5 2 seconds to reach the popliteal artery and another 7 4 seconds (for a total
of 36 seconds) to reach the ankle. If the contrast travel time to midcalf is <25 seconds, the
patient is considered to have rapid circulation. If the time is >30 seconds, the circulation is
considered to be slow. In patients with rapid arteriovenous transition, the arterial phase window
is extremely short and venous enhancement occurs immediately after the contrast arrival in the
arteries. Time-resolved MRA also demonstrates if there is an asymmetry in contrast arrival
times between the legs. In these cases, bolus timing should be adjusted according to the
symptomatic leg or the side with the slowest flow since late is better than early. In fast-flow
patients or patients with rapid arteriovenous shunting, it is desirable to keep the acquisition time
20 seconds for the first station. A subsystolic thigh compression is essential, along with an
acquisition time of 16 seconds for the second station and ~40 seconds for the third station
along with elliptical centric ordering of the k-space. By using fewer phase encoding steps,
partial phase FOV, parallel imaging, or fewer slices, data acquisition can be accelerated.
FIGURE 7-9. (A) Abdomen-pelvis and (B) thigh stations of bolus chase 3D CE MRA. Note
the long segment vessel wall irregularity and signal drop in the proximal left superior
femoral artery seen on the thigh station (arrows). However, on the abdomen-pelvis station
these are not found. Adequate overlap (3 to 4 cm) at the levels of the common/superficial
femoral arteries and the popliteal arteries is important for visualizing these segments on at
least one station and avoiding misinterpretations caused by bolus timing errors.
Older individuals (>70 years) and patients with heart failure and/or abdominal aortic aneurysms,
tend to have slower blood flow (time to calf, >30 seconds) (88). In these patients, it is possible
to get ahead of the bolus before the complete filling of the thigh and calf arteries, if data
acquisition is too rapid. In addition, Gd arrival can be delayed in vessel segments distal to
stenoses or occlusions. Therefore, in patients with slow flow, the first station can be a few
seconds longer (up to 25 seconds). The second station can be up to 20 seconds with
sequential k-space ordering instead of elliptical centric ordering. The third station can be up to 1
minute long with 512 ~ 512 resolution and repeated twice to capture the arteries in the
occasional patient with extraordinary slow flow.
Evaluation of the peripheral vascular diseases usually requires assessment of long vessel
segments. Therefore, a large FOV is essential to maximize anatomic coverage. For optimal
positioning of the 3D slabs of a bolus chase MRA, a fast threeplane T1-weighted localizer, as
well as a 2D TOF localizer with a slice thickness of 5 mm, is required at all stations. A 2D TOF
localizer pulse sequence usually takes only 30 to 60 seconds per station. The coronal slabs of
the 3D CE MRA acquisitions are then prescribed on the 2D TOF projection images. The slabs
should overlap at the regions of common femoral artery bifurcation and the popliteal artery
trifurcation, so that these regions are visualized on at least one of the stations, ideally on both
stations in two different contrast phases (Fig. 7-9). The imaging volumes for 3D MRA are
prescribed in the coronal plane to minimize the thickness and number of slices. The coronal
volume can be obliqued according to the sagittal projection images of the TOF localizer
acquisitions. The number and thickness of the slices should be adjusted to obtain sufficient
coverage while the imaging times are optimized to keep up with the flow of the contrast bolus
down the legs.
DATA PROCESSING AND PRESENTATION

Data processing is an important aspect of 3D CE MRA. Most referring clinicians are more
comfortable with images resembling DSA, rather than hundreds of source images.
Digital Subtraction
The subtraction of the precontrast mask 3D data set from the postcontrast 3D MRA data set
eliminates the residual
background signal from stationary tissues, improves image contrast, and creates images like
DSA. Two types of subtraction are used for MRA: First, the complex subtraction that is applied
before Fourier transformation and, second, magnitude subtraction after Fourier transformation.
Complex subtraction is more effective, particularly for visualizing arteries that are smaller than
the slice thickness (89).
Subtraction can be applied to MRA examination of any vascular territory; however, it works
best for the lower extremities, where motion is minimal and background signal is troublesome,
particularly in evaluating the small vessels of the calf and the foot. Any motion in between the
pre- and the postcontrast image acquisition or unequal inspiration level during theses
acquisitions, however, leads to misregistration and thereby worse image quality compared with
the nonsubtracted images and emphasis of artifacts. Subtle artifacts are more problematic,
because they may lead to under- or overestimation of stenoses in small vessels.
Subtraction is particularly useful in MR venographic studies because the CNR of MR
venographic images is inherently lower compared to that of MR arteriograms, and veins are
superposed in most of the areas by the arteries. Subtraction of the arterial phase from a
delayed phase may improve visualization of veins by removing adjacent arterial structures. Fat
suppression can be helpful. The improvement in SNR can be more prominent with fat
suppression compared to the subtraction technique, at the expense of a slightly lengthened
acquisition time.
Zero-Filling
Zero-filling is a data interpolation method to increase the number of overlapping reconstructed
slices without sacrificing SNR. Zero-filling can be applied in either the slice-select or the in-plane
direction. This technique involves filling out the peripheral lines of the k-space with zeros before
Fourier transformation, thereby expanding the k-space without increasing the acquisition time.
The interpolation is proportional to the amount of zeros. In general, twofold zero-filling in the
slice direction is routinely used to enhance resolution and creates twice as many slices, with a
50% overlap of each slice. For example, if the partition thickness is 3 mm, Fourier transform
with twofold zero-filling will reconstruct additional images that also have a 3-mm slice thickness
but with 1.5-mm spacing and 50% overlap. Zero-filling in the slice-select direction increases the
number of overlapping reconstructed slices without sacrificing the SNR.
Although the true resolution of the reconstructed images does not increase, zero-filling
technique helps to eliminate volume-averaging artifacts and creates smooth-contour displays of
vessels on the MIP images by reducing the stairstep artifact, which may be a problem on
oblique MIPs.
Reconstruction Techniques
Each 3D reconstruction technique has its own strengths and weaknesses that can lead to
artifacts and interpretation errors.
Multiplanar reformations (MPRs) and subvolume maximum intensity projections (MIP) are
extremely helpful for evaluating the vascular anatomy, especially when they are not oriented in a
single plane. MPRs are single-voxel planar reconstructions through the 3D volume. Reformatted
images can be produced in any desired plane including curved planes. MIPs are 2D
reformatted images that are generated from the 3D data set and can be acquired in any plane
at any obliquity by using a ray tracing algorithm. The algorithm generates rays perpendicular
to the subvolume and the highest voxel value along the ray becomes the pixel value of the 2D
MIP image (90). The thickness and orientation of the MIP images are determined based on the
vascular structures to be included. Since these subvolume projection images are thin (typically 1
to 2 cm), the overlapping structures on the projection images are eliminated and there is high
vascular signal compared to background (Fig. 7-10). Thin reformatted images are particularly
valuable for subtle intraluminal details and branch vessel origins.
Multiple MIP projections are helpful to avoid underestimating stenosis severity, particularly if it is
caused by an eccentric plaque that is seen in only one plane. When the vascular structure is
tortuous, a thin slice may not cover the entire vascular segment. In this case, thicker MIPs
(combined multiple slices) are required to illustrate the entire course of the vessels. Thick
subvolume MIP images, however, may result in overestimation of the severity of stenosis in a
small-caliber vessel. However, if the slice is too thick, the overlapping signals from the
background tissues or the other vessels may obscure the ROI. When a superimposing structure
has a higher signal intensity than the vessel of interest, such as enhancing stationary tissue,
veins, fat, and hemorrhage, pixels with a high signal intensity can be mismapped onto the MIPs.
This may cause an interruption of the vessel signal and mimic a stenosis or occlusion.
Additionally, single-projection MIPs may lead to missing a dissection or a mural thrombus and,
thus, to underestimation of the vessel diameter. Thus, analysis of the 3D data should always
include review of the individual source images in addition to reformatted images.
Overall image quality of the MPRs and MIPs can be improved by manually removing the
artifacts and undesired background signals from the entire 3D data set prior to reformatting.
Another postprocessing technique, known as volume rendering, creates a 3D display of the
vessels by illuminating through the background and enhancing surfaces. Volume rendering is
particularly useful for showing the relationships between vessels and organs. Vascular
segmentation allows tracking the vessel based on signal intensity and removing the vessel from
the 3D data set.
COMMON PITFALLS AND ARTIFACTS

Despite innovations in both pulse sequences and 3D reconstruction techniques, some pitfalls
and artifacts remain. This is especially true if the source data are poor in quality. Therefore,
recognizing and avoiding these pitfalls and artifacts is crucial, and they must be minimized with
careful attention to technique.
Metal Artifacts
Metallic susceptibility artifacts from surgical clips, prostheses (i.e., hip or knee prostheses) and
intravascular stents can easily obscure visualization of the vascular territory of interest or
simulate stenosis or occlusion due to the signal dropout caused by susceptibility effects of
metal (Fig. 7-11). There are not many options to avoid the artifacts from large metal objects,
although increasing the receiver bandwidth and flip angle and minimizing the TE may help limit
the amount of signal void caused by endovascular stents (59,91, 92, 93, 94, 95, 96). A metal
artifact can be identified by a characteristic bright buildup of a signal on one side of the signal
void, which is not seen with a real stenosis or occlusion of the vessel. An unsuspected stent
may mimic a vascular stenosis or a short segment occlusion. Inspection of the 2D pre- and
postcontrast images as well as the 3D CE MRA source images for characteristic signal dropout
from metallic susceptibility artifact is always helpful.
FIGURE 7-10. A 95-year-old woman with a history of renal insufficiency was referred for
renal MRA. A: Three-dimensional CE MRA demonstrates the widely patent single right
renal artery (open arrow) and pelvic location of the left kidney (*). B: Sagittal oblique
subvolume MIP reconstruction demonstrating the widely patent artery of the ectopic kidney
(arrow).
FIGURE 7-11. A: A 79-year-old woman referred for evaluation of the aortic stent. A:
Three-dimensional CE MRA (TE, 1.3; TR, 5.9], 40 mL Gd. The signal drop in the infrarenal
abdominal aorta is caused by the nitinol aortic stent. Note that, with the same pulse
sequence parameters, (B) steel stents in the renal arteries completely obscure the stent
lumen, (C) whereas a nitinol stent in the infrarenal abdominal aorta does not cause signal
drop as severe as with steel stents in the renal arteries.
Pseudo-occlusion
When a segment of the vessel is not included in the imaging volume, it may mimic a stenosis or
occlusion. Therefore, whenever a stenosis or an occlusion is seen in the common femoral
artery, which is the most anterior, or in the common iliac or popliteal arteries, which are the
most posterior, it is important to check that the imaging volume has been extended sufficiently
in the anterior and the posterior directions to cover these arteries.
Arterial pseudostenosis can also be seen when the Gd concentration within an overlying vein is
very high. High concentrations of Gd cause T2* susceptibility artifacts, similar to the metallic
susceptibility artifact, which in turn obscure the adjacent artery and lead to the erroneous
appearance of an arterial stenosis (97). This artifact is most commonly seen in the subclavian
artery due to the antecubital venous injection of Gd chelates. If this is not a true lesion, the
obscured vessel segment should be visible on the second or third phases of the dynamic study.
Ringing Artifact and Venous Contamination

One of the most common issues in CE MRA is coordinating data acquisition with contrast bolus
arrival. Errors in bolus timing are difficult to eliminate, and any timing error results in low arterial
SNR.
When the center of k-space data is sampled before the Gd concentration peak in the artery, an
edge ringing artifact occurs (98). Ringing artifact can be recognized as alternating black and
white lines paralleling vessel edges on MR angiograms. This artifact can be avoided by adding
an additional 5 seconds to the contrast arrival time while calculating the exact scan time. The
additional time ensures that the contrast rise time is completed and the contrast concentration
is at a plateau before initiating the actual acquisition (22).
Alternatively, recessed elliptic centric k-space acquisition schemes can be used to delay k-
space center acquisition for a few seconds from the beginning of data acquisition (99,100).
If the center of the k-space is encoded too late, the enhancement of the veins and the
background may be excessive. Even when the acquisition is timed well for the arterial phase,
some patients may have very fast arteriovenous circulation and thus there will be virtually no
window to obtain a pure arterial phase image. Nearly instantaneous venous filling also occurs
when there is an arteriovenous fistula, an arteriovenous malformation, or cellulitis. The best way
to evaluate these patients is to perform a time-resolved MRA technique with high temporal
resolution.
Aliasing (Wraparound) Artifact

Aliasing occurs when the FOV is narrower than the body part that is being imaged in the phase
encode direction. This rarely occurs with peripheral MRA when using a full FOV, unless it is
highly rectangular. It is always useful to check the precontrast mask images for aliasing artifact,
so that the FOV can be increased as necessary. Since this artifact occurs on both the mask
and the arterial phase images, it can be eliminated by subtraction as long as there is not
significant motion. When using parallel imaging, aliasing artifact is more difficult to remove after
data acquisition so extra care must be taken to avoid aliasing with parallel imaging.
Magnetic Resonance Angiography Applications and

Interpretation for Selected Clinical Conditions
MRA is an effective noninvasive diagnostic tool in planning surgery, endovascular and surgical
interventions, and follow-up evaluation of the stents and grafts. MRA applications and
interpretation should be tailored according to the clinical issues important for the individual being
scanned. For example, if a percutaneous intervention is being planned, assessment of the
vascular access site should be a part of study. The most common vascular access site is the
common femoral artery, thus this vessel segment should be included in the imaging volume
whenever an aortic or peripheral arterial disease is a concern.
Atherosclerotic Disease of the Abdominal Aorta and Lower

Extremity Arteries
It is important to use standardized terms for describing the patency of vascular segments to
minimize confusion in reporting. Arteries are graded as occluded, severe stenosis (>75%
narrowing), moderate stenosis (50% to 75% narrowing), mild stenosis (<50% narrowing), and
normal or widely patent. Arteries can be ectatic (up to 50% above normal diameter) or
aneurysmal (>50% over normal diameter) (Fig. 7-12).
Popliteal artery disease or reconstitution via the collaterals should be described according to
the knee joint level (i.e., above
the knee, at the knee, below the knee), because above the knee disease can be bypassed with
synthetic materials, while below the knee disease can only be treated by vein graft.
FIGURE 7-12. Three-dimensional CE MRA of the thighs demonstrates distal superficial
femoral artery and popliteal artery aneurysms in the right leg. In the left leg, there is a vein
graft anastomosed to the left superficial femoral artery (open arrow). Note the mild
stenosis in the proximal segment of the graft (curved arrow).
FIGURE 7-13. (A) Intra-arterial DSA and (B) 3D TRICKS CE MRA of the left calf arteries.
The distal segment of the superficial femoral artery-to-anterior tibial artery vein graft is
widely patent. Anterior tibial artery is occluded distal to the graft anastomosis site
(arrows). The peroneal and the posterior tibial arteries are occluded proximally but
reconstituted in the midcalf via the muscular collaterals.
Pedal bypass graft surgery may be the only treatment option for limb salvage in patients at risk
of limb loss (101). Therefore, while describing occlusive disease of the runoff vessels,
particularly in patients with critical limb ischemia, the level that has no disease as well as runoff
vessels contiguous with the pedal arteries should be documented to identify a suitable distal
artery for bypass grafting to the foot (Fig. 7-8).
The dorsalis pedis, posterior tibialis, plantar branches, and arch are all possible distal
anastomosis sites to salvage the limb in patients with critical ischemia. Two-dimensional TOF
MRA has been found to be accurate and cost-effective in evaluating occlusive diseases of the
lower extremities and, if properly performed and interpreted, is sufficient for planning peripheral
bypass procedures (80,102). The accuracy of 2D TOF MRA has been found to be significantly
higher than that for conventional angiograms for the medial plantar, lateral plantar, and plantar
arch arteries of the feet (103). High-resolution 2D TOF MRA of the small runoff and foot
vessels has been shown to have a greater sensitivity compared with intra-arterial DSA and may
facilitate successful bypass surgery and improve the overall limb-salvage rate (80,104, 105,
106). TOF techniques provide high-SNR angiograms, especially when the blood flow is slow,
which is not unusual with extensive, multilevel occlusive disease of the proximal arterial
segments. Some authors have also concluded that 2D TOF MRA is superior for evaluating the
small runoff and pedal vessels compared with 3D CE MRA due to the problems associated with
CE MRA techniques, including bolus delay and dilution as it travels through multiple collateral
vessels, venous contamination, background tissue enhancement, and inadequate temporal
resolution, that may degrade 3D CE MRA to be nondiagnostic (107). However, when 3D CE
MRA is optimized for high-resolution acquisition, it can and should replace 2D TOF MRA in this
application (42). The sensitivity and specificity of calf and pedal MRA compared to those of
DSA are >80% and 90%, respectively (108, 109, 110) (Figs. 7-1 and 7-7).
Three-dimensional CE MRA is a also a useful diagnostic method for postsurgical evaluation of
bypass grafts and recurrent disease in the graft lumen. The accuracy of 3D CE MRA in
detecting disease in bypass grafts is equal to that for native arteries (44,111) (Figs. 7-12, 7-13
and 7-14).
Cine PC flow measurements in occlusive peripheral arterial disease can be helpful for
determining the severity of stenoses. Peripheral arteries show a high-resistance triphasic flow
pattern at rest. However, ischemia, similar to exercise, leads to a decrease in capillary
resistance, which in turn causes a low-resistance (mono-or biphasic) flow (112). If the
waveform in a peripheral artery has a high-resistance flow pattern proximal to the stenosis and
a mono- or diphasic pattern distal to the stenosis, the occlusive disease is hemodynamically
significant. A decreased peak flow velocity and delay in peak velocity below the occlusive
disease show a significant positive correlation with the hemodynamic significance of the lesion
(31) (Fig. 7-2).
Abdominal Aorta Aneurysm

AAA is one of the most common manifestations of atherosclerosis. The location, length, and
maximum diameter of the aneurismal segments should be described in detail, with
documentation of the interval progression or regression from previous examinations. These
patients also need to be evaluated for accessory renal arteries as well as the coexisting renal
and/or mesenteric artery stenoses prior to any interventional or surgical planning. Failure in
determining these conditions prior to surgery may lead to associated postoperative
complications such as renal failure or mesenteric ischemia (113). Aneurysms may extend into
the common iliac arteries, and demonstrating this extension also affects the decision making.
The most significant risk of AAA is rupture, and the risk of rupture is high for aneurysms with a
diameter of 5 cm or those that show an average growth rate of >0.5 cm per year (114).
FIGURE 7-14. A: Three-dimensional CE MRA of the abdominal aorta and inflow vessels
demonstrating complete occlusion of the infrarenal abdominal aorta extending to both
common femoral arteries (arrows). Note that the collateral vessels in the abdominal wall
reconstitute the inferior epigastric and profunda femoral arteries. B: Subvolume coronal
MIP confirms the thrombosis of the aortobifemoral graft lumen (open arrows).
Although the etiology of AAA traditionally has been attributed to atherosclerosis, a number of
other pathologic conditions, such as noninfectious inflammation or infection, may also cause or
contribute to aneurysm development (115, 116, 117, 118, 119, 120). Atherosclerotic aneurysms
tend to be fusiform in morphology and commonly involve the infrarenal abdominal aorta.
Uncommon suprarenal AAAs usually extend into the thoracic aorta, whereas infectious
aneurysms tend to be eccentric saccular/lobulated in morphology (119), can be localized
anywhere, and may be associated with stenosis of the distal aorta, which is very unusual with
atherosclerotic AAA. Besides, infectious aneurysms can progress very rapidly and show
accompanying infectious findings, such as vessel wall enhancement, abscess formation, and/or
retroperitoneal fat tissue inflammation (Fig. 7-15). Noninfectious inflammatory aneurysms, such
as Takayasu arteritis, however, demonstrate different pathological and radiological findings in
addition to the aortic dilatation (Chapter 2). Fibrotic components of the pathology may cause
focal stenoses in the aorta and its main branch origins in addition to the aneurysms.
If a nonsurgical approach is preferred, MRA is the choice of imaging technique to follow interval
change in size of the AAA, as well as associated pathologies (118,120). For example,
increased enhancement of the vessel wall is a sign of activation of the inflammatory aortitis and
is best evaluated with postcontrast black blood MRA techniques, such as fat-suppressed spin
echo or double inversion recovery pulse sequences. Assessments of the pre- and postcontrast
images are useful for identifying atherosclerotic plaques, intraluminal thrombus, and wall
thickening or enhancement in patients with suspected inflammation.
Branch vessel involvement is best illustrated with 3D CE MRA (121). Another important element
of the disease is thrombus formation in the aneurismal segment, which can embolize distally.
MRA, therefore, is advantageous over DSA, because conventional angiography images usually
fail to demonstrate thrombus.
Aortic Dissection
Aortic dissection is the pathological condition in which the blood dissects into the media of the
aortic wall through an intimal tear. The intimal flap subsequently separates the lumen into a
false and a true lumen. The branch vessels arising from the false lumen may have compromised
blood flow due to the slow, low-pressure flow in the false lumen. Branches arising from true
lumen may also be compromised due to intermittent
obstruction by the intimal flap collapsing onto the origin. The most frequently involved vessel is
the left renal artery, followed by the celiac trunk and superior mesenteric artery. Dissection may
extend into branch vessels, especially the great vessel and the common iliac arteries. For
adequate visualization of the false lumen with slow flow, at least two delayed-phase 3D CE
MRA should be acquired. Unequal perfusion of the kidneys in the arterial phase, particularly in
association with new-setting hypertension or renal insufficiency, may require urgent intervention
(Fig. 7-16).
FIGURE 7-15. (A) Three-dimensional CE MRA and (B, C) coronal subvolume MIP
reconstructions on the arterial and venous phases. Infrarenal abdominal aorta aneurysm
with wall enhancement on the venous phase that is consistent with inflammation.
Renal Artery Stenosis, Fibromuscular Dysplasia, and Renal

Artery Aneurysm
Three-dimensional CE MRA examination of the renal arteries has been shown to be very
sensitive and specific for detecting renal artery stenoses (RAS), and this application is now
widely used in clinical practice (122, 123, 124, 125, 126). Although most renal MRA
examinations are requested in patients with hypertension and a clinical suspicion of RAS,
dedicated renal artery MRA should also be considered while evaluating peripheral vascular
disease and coronary arteries, because atherosclerotic occlusive disease of renal arteries has
been shown to occur in 30% to 50% of patents with peripheral arterial disease and/or aortic
aneurysm and 40% of patients undergoing cardiac catheterization (127, 128, 129, 130). Three-
dimensional 3D CE MRA has been proposed and used as a screening tool for patients with
suspected renovascular hypertension, because it does not expose the patient to ionizing
radiation and nephrotoxic iodinated contrast agents (131). Potential harms of DSA and CT
angiography have always been a concern, particularly in patients with impaired renal function,
who are more likely to require further renal artery evaluation and endovascular revascularization
procedures. The Gd chelates used in 3D CE MRA, however, are safe even in patients with
renal insufficiency, in limited doses (132). Additionally, all commercially available MR scanners
have pulse sequences that can be used for measuring blood flow and renal perfusion for
comprehensive assessment of kidney functions.
While atherosclerotic disease of renal arteries accounts for 90% of patients with RAS,
fibromuscular dysplasia (FMD) is another cause of renovascular hypertension (133,134). FMD
mainly affects the mid and distal segments of the renal arteries, unlike athereosclerosis, which
mostly involves the ostium and proximal segment of the vessel. However, one third of FMD
cases can present with involvement of the proximal segments of the arteries, which causes a
characteristic string-of-beads appearance due to the intervening focal dilatations and stenoses.
MRA is not as powerful a technique for assessing the distal segments of the renal arteries due
to the motion that occurs despite successfully suspended respiration (135). Therefore,
evaluation of renal arteries for FMD is a challenging application of 3D CE MRA. Both false-
positive and false-negative examinations are common, probably related to inadequate spatial
resolution as well as the subtle motion of the kidneys (136). For renal 3D CE MRA, the spatial
resolution should be at least 1.5 mm3 (137) (Fig. 7-17).
FIGURE 7-16. An 80-year-old woman with progressive hypertension. Three-dimensional
CE MRA of the abdominal aorta demonstrates a dissecting aneurysm of the abdominal
aorta extending from the thoracica aorta to the left common iliac artery. The signal of the
true lumen (open arrow) is higher than that of the false lumen (arrow). The right renal
artery takes off from the true lumen, whereas the left renal artery arises from the false
lumen. Note that the left kidney perfusion (curved arrow) is delayed compared with the
right kidney.
FIGURE 7-17. A 51-year-old man with refractory hypertension. High-resolution 3D CE
MRA of the renal arteries. Imaging parameters as follows: FOV, 350 mm; slice thickness,
1.8; matrix, 512 512; TR, 4.2 milliseconds; TE, 1.1 milliseconds; Gd, 40 mL. Bilateral
single renal arteries are widely patent.
In patients with high-grade renal artery stenosis, MRA can show collateral vessels through
capsular and perforating arteries. Poststenotic dilatation may be seen in 20% of patients with
hemodynamically significant stenosis and tend to be eccentric in position (138). The
hemodynamic relevance of a RAS can also be evaluated by using cine PC flow measurements
(139,140). A normal renal arterial flow pattern demonstrates an early systolic peak velocity, a
dicrotic notch, and a second, smaller midsystolic peak. Mild stenosis leads to a partial
decrease in the early systolic peak; moderate stenosis causes an almost-complete loss of the
early systolic peak and a partially preserved midsystolic peak. In case of high-grade stenosis,
flow is flattened, without an early or midsystolic peak (141). Combined with 3D CE MRA, cine
PC flow measurements have been shown to have increased accuracy for determining the
severity of occlusive disease in renal arteries (138,142,143). Combining 3D PC with 3D CE
MRA also improves the accuracy in determining the severity of stenosis in the renal arteries
compared with 3D CE MRA-only evaluation (32,140,144,145). Three-dimensional CE MRA
tends to overestimate the degree of stenosis due to the limited spatial resolution and 3D PC
MRA can differentiate mild to moderate stenosis from hemodynamically significant stenosis.
The signal loss on 3D PC MR angiogram reflects the loss of phase coherence due to the
acceleration of the flow velocity and the turbulent flow in the poststenotic vessel segment,
which occurs with a proximal narrowing of the cross-sectional area of >70% (32) (Fig. 7-3).
Approximately half of patients with renal artery aneurysms are diagnosed during arteriographic
studies for renovascular hypertension. Renal artery aneurysms are associated with
hypertension (73%), FMD (34%), atherosclerosis (25%), and extrarenal aneurysms (6.5%) and
tend to be saccular and noncalcified. The main renal artery bifurcation is the most common site
(60%) (146) (Fig. 7-18).
Accessory Renal Arteries

The frequency of accessory arteries varies from 25% to 61% of cadavers (147). Accessory
renal arteries tend to be tortuous, smaller, and longer compared with the main renal arteries.
Therefore, accessory arteries provide a lower perfusion pressure and higher vascular
resistance compared with the regular renal arteries (148). Some authors have reported that an
isolated accessory renal artery stenosis, with patent main renal arteries, can produce
renovascular hypertension (147,149, 150, 151). The significance of accessory artery stenosis,
however, remains controversial, because the the prevalence of isolated hemodynamically
significant accessory renal artery stenosis is very low (151) and interventional procedures carry
a high risk of occlusion of these small-caliber vessels. Besides, some authors have found no
statistically significant difference in the prevalence of renal artery stenosis between patients
with accessory renal arteries and those without accessory renal arteries, and concluded that
the presence of accessory renal artery is not a direct cause of hypertension (148).
Although some investigators have concluded that sacrificing accessory renal arteries during
endovascular stent placement is well tolerated by patients even if there is a coexisting renal
impairment (152), identifying accessory renal arteries prior to the intervention is still important
to avoid segmental infarction of the kidneys.
The accuracy of 3D CE MRA in identifying the accessory arteries has been reported as
between 80% and 100% (125,126,153) (Fig. 7-19).
Endovascular Stent Grafts: Pre- and Postintervention

Evaluation
Endovascular stent grafting is an increasingly common treatment option in patients with AAA
and requires routine imaging surveillance (154,155). Prior to the intervention, determining the
length and the maximum diameter of the aneurismal segment as well as the normal aorta is the
most important issue to customize the graft. While measuring the length of the vessel
segments, the tortuosity, which is commonly associated with AAA, must be taken into
consideration to measure the
true length of the vessel in the craniocaudal direction. The true diameter of the aneurysmal
segment is also important. The endograft must be a few millimeters larger than the vessel
diameter at the proximal neck area. The distance of the aneurysm neck from the renal arteries
should be at least 15 mm for adequate sealing of the proximal neck without excluding the renal
arteries. Inadequate sealing leads to Type 1 endoleak and, thereby, early failure in treatment.
Endografts too large for the vessel tend to fold and may leak; endografts too long for the
vessel may kink and cause thrombosis or occlusion. Although DSA and CE CT angiography are
commonly used for detecting and classifying endoleaks, 3D CE MRA can also identify and
characterize endoleaks (156,157). High-speed gradient technology has facilitated the use of
MRA for detecting early endoleaks by enabling time-resolved CE MRA acquisitions with
adequate temporal resolution (Fig. 7-20). Real-time review of the vascular structures can be an
effective noninvasive alternative method for detecting and classifying endoleaks, as well as
screening of patients with endoleaks to identify those requiring urgent repair (157).
Nevertheless, the presence or absence of an endoleak does not indicate either failure or
success of the procedure and thus should be assessed by the interval change in aneurysm size,
adequacy of the stent graft position with respect to the renal arteries, integrity of the device,
and change in characteristics of a known endoleak.
FIGURE 7-18. A 32-year-old woman with neurofibromatosis. A: Three-dimensional CE

MRA of renal arteries demonstrates a renal artery aneurysm on the left side. There is a
short segment moderate to severe stenosis (arrow) of the renal artery just proximal to the
saccular aneurysm. B: Intra-arterial DSA findings are identical to MRA findings.
FIGURE 7-19. A 39-year-old woman with hypertension was referred for renal artery
evaluation. 3D CE MRA demonstrates widely patent main and accessory renal arteries on
both sides.
Revascularization Procedures: Pre- and Postintervention

Evaluation
Angioplasty and postangioplasty endoluminal stent placement for preventing restenosis are
currently common practice. However, these revascularization procedures are not
complication-free and, thus, require careful evaluation of the severity of the stenosis before
deciding on intervention. In current clinical practice, the hemodynamic significance of the
stenosis is determined by measuring the transstenotic pressure gradient with invasive
catheterization. However, 2D and 3D PC MRA may replace invasive catheterization, because
noninvasive evaluation of the hemodynamic significance of the stenosis is possible using PC
flow MRA techniques (Figs. 7-2 and 7-3).
FIGURE 7-20. An 81-year-old man with a nitinol aortic stent graft. A: Coronal source
image on the arterial phase of blood-pool agent enhanced 3D MRA demonstrates a small
endoleak (arrows). B: On coronal MIP note the enlarged enhancement due to the slow
endoleak at 17 minutes. C: DSA following selective injection into the left internal iliac artery
shows collateral reconstitution of a lumbar artery (curved arrow) with retrograde filling of
the aneurismal sac. D: Axial CT image on the arterial phase also demonstrates the
endoleak.
Metallic implants, such as stents, lead to two types of susceptibility artifacts: The artifact
arising from metal-induced local field inhomogeneities (92) and perturbation of the transmit and
receive sensitivities of the rf coils due to the eddy currents in the metallic implant (59). The
diagnostic imaging performance of MRI depends mostly on the magnetic properties of the
stent, such as the material used in stent construction, geometry of metal reconstruction, and its
orientation with respect to the main (B0) magnetic field. Stents oriented parallel to B0 cause
fewer magnetic susceptibility artifacts compared with stents perpendicular to B0 (96). Metallic
stents cause artifacts due to susceptibility differences between the metal and the neighboring
tissues. While the susceptibility-induced field disturbance is the major cause of signal loss inside
and in regions surrounding ferromagnetic steel stents, this is less of an issue with stents made
of MR-compatible nitinol, platinum, or tantalum (92,93,96) (Fig. 7-11). The severity of the
susceptibility artifact also depends on the total metal mass in the implant. Thinner stents cause
less susceptibility artifact. Although steel stents are thinner than nitinol or tantalum stents, they
cause more pronounced susceptibility artifact, because ferromagnetic eddy currents overwhelm
this property. Metallic susceptibility artifacts are typically more pronounced at the ends of the
stents due to the intravoxel phase distortions (93).
Other factors influencing the severity of metallic susceptibility artifact include the pulse
sequence, TE, imaging
bandwidth, flip angle, readout direction, and magnetic field strength (91,92,95,96). Gradient
echo pulse sequences do not utilize a 180-degree refocusing pulse and are, therefore, more
vulnerable to the magnetic field inhomogeneities that arise from the difference in susceptibility
between the stent and its surroundings. Metal susceptibility artifact can be minimized by either
using an ultrashort TE (94) or selecting a wider receiver bandwidth by decreasing the risk of
intravoxel dephasing. A wide bandwidth, however, sacrifices the SNR. Reducing the frequency
encoding steps, using fractional echo, and/or avoiding partial Fourier imaging can also achieve
a shorter TE (93). The Faraday cage effect of the stent mesh attenuates the rf signal and
reduces the flip angle within the stent. This can be partially overcome by using a higher (such
as 75-degree) flip angle (95,96).
Endovascular implants that are not well attached to the vessel walls may cause turbulent flow,
which also enhances intravoxel spin dephasing and signal loss in the vessel lumen. This
condition may lead to a false interpretation of a stenosis or overestimation of stenoses.
Although intravoxel dephasing is a well-known artifact of noncontrast TOF MRA techniques, this
phenomenon is less prominent with 3D CE MRA.
Presurgical Abdominal Vascular Roadmapping for Organ

Transplantation
MRA is a valuable method for noninvasive roadmapping for a variety of surgeries, including
hepatic resection and transplant planning, as well as screening of potential kidney donors (158).
MRA can provide the crucial information without exposing the potential donor to potential and/or
unavoidable complications of DSA or CT scans, such as ionizing radiation or nephrotoxic
iodinated contrast agents. When evaluating potential donors, issues that should be taken into
consideration include determination of the most suitable kidney for expedient and safe removal,
identification of the number and the origins of renal arteries and veins, and determination of the
presence of any early-branching arteries. MRA also allows the detection of unsuspected
renovascular disease or parenchymal disease, as well as congenital anomalies, such as ectopic
kidney (Fig. 7-10), retroaortic or circumaortic renal veins, and anomalous drainage of the renal
veins.
FIGURE 7-21. A 56-year-old woman with increasing creatinine level was referred for
evaluation of the transplant renal artery. A: Three-dimensional CE MRA shows the
transplant kidney in the right pelvis and aortic graft (arrows). Note the severe stenosis at
the origin of the common iliac artery and poststenotic dilatation. B: Subvolume coronal MIP
confirms a widely patent transplant renal artery with no stenosis at the anastomosis site to
the external iliac artery (open arrow). The renal vein is also patent.
Renal Transplant Evaluation

Three-dimensional CE MRA has recently become a standard of care in assessing transplant
kidneys. The pelvic localization of the transplant allows long scan times for high-resolution
imaging. The 3D data set allows multiplanar reformatting of the complex vessel anatomy
associated with renal transplants. Stenosis of the transplant kidney artery is the most common
vascular complication of renal transplantation, occurring in 1% to 12% of transplanted renal
arteries (159,160). Compared with DSA, 3D CE MRA has a sensitivity of 100% and specificity
between 93% and 97% for detecting and grading transplant renal artery stenosis (161) (Fig. 7-
21). However, attention should be paid to differentiate hemodynamically stenosis from mild
narrowing or kinking. PC MRA has also been shown to be valuable in determining the severity
of stenosis (142,162). Other potential complications that can be demonstrated with MRA
include arterial and venous thrombosis, intrarenal arteriovenous fistulas and pseudoaneurysms
secondary to transplant biopsy, and urinary leaks.
FIGURE 7-22. A 30-year-old woman with low flow velocity in the mid- and distal radial
artery. A: Upper extremity MRA study; widely patent axillary artery-to-radial artery bypass
graft with no stenoses at the anastomosis sites (curved arrows). B: Magnified view of the
distal station demonstrates weblike stenoses in the proximal segment of the radial artery
(arrow).
FIGURE 7-23. Hemodialysis graft surveillance study. A: Three-dimensional Gd-enhanced
MRA of the right arm shows a hemodialysis graft anastomosed to the axillary artery and
basilic vein. B: MIP image demonstrates severe stenosis at the arterial anastomosis site.
Upper Extremity Magnetic Resonance Angiography and

Surveillance of Dialysis Grafts
Peripheral CE MRA techniques can be modified for upper extremity MRA examination. This
includes 3D TRICKS of the forearm and 3D CE MRA of the central vessels and the upper arm.
Bolus timing can be managed by MR fluoroscopic monitoring of the contrast agent into the
contralateral subclavian artery with a scan delay of 5 seconds (Fig. 7-22).
Surveillance of dialysis grafts is one of the most recent indications of 3D CE MRA (163, 164,
165, 166). Thrombosis of the graft, arterial or venous end, as well as stenosis of the
anastomoses can be detected by CE MRA (Fig. 7-23). Additionally, MRA is able to depict a
proximal stenosis or thrombus in the subclavian and brachial vessels.
SUMMARY
MRA is a noninvasive, fast, safe, and accurate imaging method for evaluating vascular diseases
and planning surgical and percutaneous vascular interventions. It has already supplanted
invasive DSA for many applications at most hospitals. The continuing advancements in
multichannel systems with wholebody multidetector arrays in combination with parallel
acquisition techniques are promising for reducing acquisition times while maintaining a high SNR
and spatial resolution. Other advances include stepping table technology, whole-body MRA
techniques, thigh pressure cuffs, continuous table motion technology, high-performance
gradients, and new contrast agents with high relaxivity. The promise of 3-T systems optimized
for vascular studies is expected to open the possibility of additional applications.
Appendix: Glossary of Terms
GLOSSARY OF TERMS
Aliasing artifact:
This artifact occurs when the FOV is narrower than the body part that is being
imaged in the phase encode direction.
Blooming artifact:
Mild stenosis causes an acceleration of the laminar flow that results in brighter
signal intensity with blooming artifact, causing one to overlook the stenosis.
Calibration scan:
As one example, motion of the patient and/or the coil array between the sensitivity
reference scan and the accelerated acquisition can lead to calibration errors and
reconstruction artifacts.
k-Space (Fourier space):
This is an array of data containing the digitized raw MR signals in a coded form,
which is a temporary storage space for the real spatial information. When acquiring
a 2D image, the matrix (no. of phase encoding steps no. of frequency encoding
steps) determines the size of the k-space, and a line of data corresponds to the
digitized MR signal at a particular phase encoding step. By applying a second
phase encoding axis to the k-space, 3D acquisition can be achieved. The 3D
imaging is usually implemented with gradient echo pulse sequences. The
advantages of 3D acquisition over 2D acquisition are the ability to acquire thinner
slices and the higher SNR. The disadvantages of 3D are longer scan times, ringing
artifact, and aliasing. While the data at the center of the k-space contain contrast
information, the peripheral k-space data contain the resolution information, in other
words, the edge details. These signal data are transformed to an MR image by
mathematical conversion, so-called Fourier transformation.
Linear (sequential) k-space acquisition:
Conventional acquisition scheme, in which the central k-space data (low spatial
frequencies) are acquired in the middle of the scan. The slice encoding (kz) is
accomplished in a regular linear fashion along the phase encode direction (ky).
Phase encoding begins from one end of the k-space and proceeds toward the
other end.
Centric k-space acquisition:
Central k-space data are acquired at the beginning of the scan. The slice encoding
(kz) is accomplished in an alternating linear fashion along the phase encode
direction (ky). Phase encoding begins from the center of the k-space and proceeds
toward the periphery of the k-space above and below the ky = 0 line that is located
in the center of the k-space.
Elliptical centric k-space acquisition:
Central k-space data are acquired at the beginning of the scan. The k-space data
are encoded in a radial fashion along both the phase encode (ky) and the slice
encode (kz) directions beginning from the center of the k-space. This acquisition
technique provides more compact central k-space data at the beginning of the scan
during the arterial peak plateau of the paramagnetic contrast agent.
Magnetic susceptibility artifact:
Bright buildup of a signal on one side of the signal void.
Parallel imaging:
Parallel imaging techniques require the use of multiple rf channels to transmit and/or
receive the MR signals. The entire image is reconstructed from an undersampled k-
space in the phase encoding direction and thus the acquisition time decreases. By
using parallel imaging techniques, the acquisition speed can be increased up to a
maximum acceleration factor equal to the number of coil array elements. With a
typical acceleration factor of 2, every other line in the k-space is skipped, therefore
the scan time is decreased roughly 50%. This reduced acquisition time can also be
traded for a higher spatial resolution at the expense of the SNR, which is inversely
proportional to the square root of the acceleration factor times a geometry factor
that is determined by the coil design.
where g is the geometry factor, which depends on the coil geometry, and R is the
acceleration factor. Each receiver coil element in an array provides information
about a distinct portion of the imaging FOV based on the spatial distribution of its
sensitivity to MR signal. Undersampling, i.e., the acquisition of a reduced number of
serial phase encoding steps, results in significant scan acceleration. Then multiple
sets of undersampled coil data are used to form a single fully sampled data set that
is required to acquire the final image.
Partial Fourier acquisition:
Number of excitation (NEX) is <1, in which the phase encode steps (ky) are
partially sampled for reducing the scan time without sacrificing the spatial resolution,
but at the expense of the SNR.
Specific absorption rate (SAR):
The total rf power absorbed in the tissues is quantified, referred to as SAR, and
indicated in units of watts per kilogram. At higher imaging frequencies, rf power is
deposited more efficiently in the conducting tissues, which will be transformed into
heat as a result of tissue resistance.
T2* susceptibility artifact:
Rapid loss of transverse magnetization and MR signal due to magnetic field
inhomogeneities.
Velocity encoding variable (Venc):
Reflects the estimated peak flow velocity in the artery of interest. Once the Venc is
set (by the operator), the scanner calculates the amplitude and the
duration of the bipolar gradient to provide a 180-degree phase shift to those spins
with peak velocity.
Zero-filling (interpolation):
In this image reconstruction algorithm, the peripheral k-space is filled by zeros
before the Fourier transformation, thereby the spatial resolution of the interpolated
image is higher (smaller pixel/voxel size) than the acquired (true) spatial resolution.
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> Table of Contents > Section II - Vascular Imaging > Chapter 8 - Endovascular Imaging: Intravascular Ultrasound, Optical
Coherence Tomography, and Intravascular Magnetic Resonance Imaging
Chapter 8
Endovascular Imaging: Intravascular Ultrasound,
Optical Coherence Tomography, and Intravascular
Magnetic Resonance Imaging
Joyoni Dey
Krishna Kandarpa
Atherosclerotic plaques at the inner wall of the arteries produce luminal narrowing and can
decrease blood flow to the end organ. When these plaques rupture, there is local thrombosis
and further abrupt compromise of the lumen. Imaging methods are needed to identify such
vulnerable plaques in order to guide interventions to increase blood flow or prevent
embolization. While some superficial arteries (carotid) can be imaged from the outside, deep-
seated arteries are optimally imaged in detail from inside the lumen.
The most established and widely used endovascular imaging modality is intravascular US
(IVUS) (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22). Figure 8-1
shows a sketch of a dual-view IVUS catheter, capable of side and forward viewing. IVUS
catheters are well integrated as an imaging feedback tool for endovascular procedures such as
stent placement (1,21). While IVUS can have deeper interrogation depths (order of a
centimeter), it is usually at the cost of resolution (>0.1 mm). One of the disadvantages of IVUS
is specular reflection from tissue interfaces that can potentially be confused with those due to
intimal thickening or calcifications. Figure 8-2 (top row in A and B) shows examples of
conventional IVUS images of lesion sites for a patient with acute coronary syndrome and
another with stable angina. Each lesion site is compared with a promixal reference image.
While conventional IVUS can detect the gross morphology of plaque, it does not have the
resolution to distinguish between different tissue components to help in the identification of
unstable or vulnerable plaques. However, sophisticated signal processing techniques applied to
high-frequency ultrasound (US) backscattered radiofrequency (rf)-receive data (before the
standard envelope detection and log-compression steps) can help distinguish the plaque
components and potential vulnerability. Virtual histology (VH) (23, 24, 25, 26, 27, 28, 29, 30) is
one such technique that uses autoregressive (AR) models to determine the power-spectral
density (PSD) of the rf-received US backscattered data. Different plaque components have
different power-spectral features. This technique has been tested in vivo and has U.S. Food
and Drug Administration (FDA) approval for clinical use (31). Figure 8-2 shows a clinical
example of VH applied to characterizing plaque tissue. The characterization of tissue
mechanical properties using elastography techniques (on the US rf backscatter data) is also
gaining in popularity (32, 33, 34, 35, 36, 37, 38, 39). Figures 8-3 and 8-4 show examples of
strain imaging or elastograms, used to detect soft fatty plaque region versus hard fibrous
regions.
Optical coherence tomography (OCT) is a relatively new modality used for IV imaging (40, 41,
42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55). Compared to IVUS, OCT typically has a
higher resolution (10-15 m) for imaging as well as a higher dynamic range (45). Another
advantage of OCT over IVUS is its lower cost and the simplicity of the hardware. Figure 8-5
shows striking superiority in the resolution of an IV-OCT image compared to IVUS. Since the
depth of field for OCT is limited to a few millimeters, catheter-mounted devices are ideally
needed for imaging blood vessels and other deep structures.
A third modality, IV magnetic resonance imaging (IVMRI), is also gaining popularity for
endovascular applications (56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72,
73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86). MRI techniques have high inherent
tissue contrast, superior to that of either IVUS or OCT, which can help identify different
components of plaque and thrombi using proton density, T1 and T2 weighting, and spin-diffusion
pulse sequences (71,74,75,83,85, 86, 87). Figure 8-6 shows an example of endovascular
IVMRI imaging with T1 weighting, proton density weighting, and T2-weighting sequences,
compared with histology. Figure 8-7 shows IVMRI images of a calcified plaque, compared to
IVUS, where the shadowing prevented the full definition of the plaque.
Different designs of endovascular MRI probes have been investigated for more than a decade.
While many of these are still in the research stage, with some animal studies performed, a
couple of designs have been used on patients recently (71,85,88).
In this chapter, we first give a brief summary of the pathogenesis of spontaneous
atherosclerosis and the importance of detecting the vulnerable plaque. We discuss the various
imaging techniques available for tissue characterization and the detection of the vulnerable
plaque. We then discuss the physics and some of the challenges behind the three main
endovascular imaging modalities. We have divided each section into an overview providing
increasing levels of complexity and detail. The main sections for each modality give an overview
and description of the state of the art and different types of devices and their advantages and
disadvantages.
ATHEROSCLEROSIS: PLAQUE GENESIS, STABILITY, AND

RESTENOSIS
Atherosclerosis
Atherosclerosis is caused by the inflammation of vascular walls following leukocyte recruitment
by dysfunctional or otherwise damaged vascular endothelium (89). The human arterial plaque
may consist of five different tissue characteristicsintimal hyperplasia, a necrotic lipid core with
a fibrous cap, fibrous tissue, calcification, and thrombus (90). A fibrous collagen cap usually
provides stability to the plaque (89). The plaques can be stable, without any progression of
stenosis, or they can become unstable, resulting in fissuring and rupture. Minor fissuring may
heal with minimal luminal encroachment of the plaque. When a vulnerable plaque ruptures,
platelets adhere to the endothelium and release various factors that are prothrombotic in nature
(91). Rupture and thrombosis can lead to acute complete occlusion (92). The unstable or
vulnerable plaque has a thin fibrous cap, thrombus at the shoulders, inflammatory cells, and a
lipid core (93). The softer the lipid core of the atheroma, the more vulnerable the plaque is to
the circumferential shear stress caused by hemodynamic forces (94). Detection and
identification of the vulnerable plaque are of vital importance for the prevention of end organ
damage.
FIGURE 8-1. Dual-view US catheter. Illustration of a simultaneously side-viewing and

forward-viewing array. (Reprinted with permission of IEEE from Wang Y, Stephens DN,
O'Donnell M. Optimizing the beam pattern of a forward-viewing ring-annular US array for
intravascular imaging. IEEE Trans Ultrason Ferroelectr Freq Control. 2002;49[12]):1652-
1664, 2002 IEEE.)
FIGURE 8-2. Fujii et al. (26) demonstrated conventional IVUS and color-coded virtual
histology (VH). A: Lesions with acute coronary syndrome, showing positive remodeling
(index, 1.05) and a plaque burden of 87%. Fibrous and fibrofatty plaques are shown to be
evenly distributed (lower right). B: Lesion with stable angina showing negative remodeling
(index, 0.88) and a plaque burden of 79%. This plaque is predominantly fibrous (lower
right). (Reprinted with permission from Fujii K, Carlier SG, Mintz GS, et al. Association of
plaque characterization by intravascular US virtual histology and arterial remodeling. Am J
Cardiol. 2005;96[11]:1476-1483.) (See the color insert.)
FIGURE 8-3. IVUS (top left) and strain imaging or elastogram (top right) with
corresponding histology, shown in bottom row. Elastogram reveals two soft (higher strain
value) regions (I and III) and two harder regions (II and IV). Histology reveals that the two
soft regions correspond to fatty regions and the two harder regions contain fibrous
material. (Reprinted with permission from de Korte CL, Pasterkamp G, van der Steen AF,
et al. Characterization of plaque components with intravascular US elastography in human
femoral and coronary arteries in vitro. Circulation. 2000;102[6]:617-623.) (See the color
insert.)
FIGURE 8-4. Schaar et al. (33) show strain patterns in coronary arteries in patient studies.
An example from Ref. 33 is shown. A: An intermediate plaque in angiogram. B: Three-
dimensional palpogram of vessel segment between white lines in angiogram. C: Cross
section of two-dimensional palpogram overlaid on echogram (IVUS). The high strain plaque
on shoulders of eccentric plaque (yellow) can be identified. (Reprinted with permission
from Schaar JA, Regar E, Mastik F, et al. Incidence of high-strain patterns in human
coronary arteries: assessment with three-dimensional intravascular palpography and
correlation with clinical presentation. Circulation. 2004;109[22]:2716-2719.) (See the color
insert.)
FIGURE 8-5. Fibrous coronary plaque imaged in vivo by (A) optical coherence tomography
(OCT) and (B) intravascular US (IVUS). The OCT image (A) demonstrates visualization of
the intima, media (m), and adventitia (a). The internal and external elastic laminae are
visible as signal-rich lines bordering the media (inset). A plaque extending from 2 to 9
o'clock contains a homogeneous, signal-rich region consistent with a fibrous plaque (f) that
is also visible in the corresponding IVUS image (B). (Reprinted with permission from Jang
IK, Bouma BE, Kang DH, et al. Visualization of coronary atherosclerotic plaques in patients
using optical coherence tomography: comparison with intravascular US. J Am Coll Cardiol.
2002;39[4]:604-609.)
FIGURE 8-6. Larose et al. (71) showed correlation of IVMRI obtained with three imaging
sequences shown in the top row (T1 weighted, proton density weighted, and T2 weighted;
1.5-T scanner) with histopathology for both morphology and tissue type in the iliac artery
for a mild circumferential plaque. IVMRI correlation with (A) shows the morphology
definition, that with (B) shows the collagen-rich area (white arrow), and, finally, that with
(C) shows the lipid-rich area (black arrow). IVMRI shows distinct signal patterns from lipid
versus fibrous tissues. (Reprinted with permission from Larose E, Yeghiazarians Y, Libby
P, et al. Characterization of human atherosclerotic plaques by intravascular magnetic
resonance imaging. Circulation. 2005;112[15]:2324-2331.) (See the color insert.)
FIGURE 8-7. Larose et al. (71) compared IVMRI with IVUS. The T1-weighted (A), proton-
density-weighted (B), and moderate T2-weighted (C) sequences illustrate a large calcium
nodule within plaque surrounded by fibrous tissue as shown in (D). The corresponding
IVUS shows hyper-echogenic signal with shadowing, precluding the entire plaque definition.
(Reprinted with permission from Larose E, Yeghiazarians Y, Libby P, et al. Characterization
of human atherosclerotic plaques by intravascular magnetic resonance imaging.
Circulation. 2005;112[15]: 2324-2331.) (See the color insert.)
Atherogenesis
The vascular wall is composed (outwards from the lumen) of the endothelium, the internal
elastic lamina, the media, the external elastic lamina, and the adventitia. In the initial stages of
atherosclerosis, the elastic wall of the vessels might remodel such that the vessel dilates,
preserving the lumen size. As the plaque progresses, however, the lumen is encroached on.
This remodeling is known as the Glagov phenomenon. Excessive intimal hyperplasia, despite
dilation of the vessel, ultimately results in luminal compromise (95).
Both the early and the advanced lesions of atherosclerosis consist of smooth muscle cells
(SMCs) and macrophages. The fatty streak is the earliest lesion of atherosclerosis and is a
lipid-rich lesion consisting of macrophages and some SMCs. The fibrous plaque, representing
more advanced atherosclerosis, is made up of increased intimal SMCs surrounded by
connective and intra- and extracellular lipid. According to the
response-to-injury hypothesis of Ross et al. (96,97), vascular injury and thrombus formation are
prerequisites for atherosclerosis. It is hypothesized that the injury to the vessel wall layers may
induce growth factor (present in all the cells involved in atherosclerosisendothelium, smooth
muscle cells, macrophages, platelets) release and autocrine or paracrine stimulation of cells in
the artery.
Other investigators have reported their observation of atherosclerosis progression (98, 99, 100,
101, 102, 103). Ip et al. (98) classified vascular injuries into three main types with increasing
severity. Type I injuries refer to functional impairment of the endothelium without morphological
damage, such as denudation. Type II refers to endothelium denudation with the internal elastic
lamina intact. Type III refers to severe damages with endothelial denudation and intimal and
medial injury. The evolution of the spontaneous atherosclerosis from Type I to Type II/III injury
may take decades. In advanced stages, however, complications such as plaque fissuring and
disruption with thrombosis (99) can occur. The transformation from angiographic insignificance
to a clinically significant obstruction can happen abruptly (100).
Restenosis
Plaque morphology is affected by procedures such as balloon angioplasty and bypass grafting.
Intimal hyperplasia or restenosis occurs within months of these procedures, since the mural
damage during these procedures resembles Type II/III injury (92,97,98,104, 105, 106, 107,
108, 109, 110). Attempts at counteracting this process of restenosis include pharmacologic
intervention and newer strategies such as drug-eluting stents, gene therapy, and endovascular
irradiation (101).
Detecting Vulnerable Plaque

Angiography and IVUS methods are currently the only FDA-approved clinical methods for the
detection of stenosis and its treatment. IVUS is the traditional method used for detection and
visualization of the plaque. While high-frequency US can identify some of the morphology of the
plaque encroaching on the lumen, by itself IVUS does not have the best resolution to identify
different components of a plaque, particularly the ability to identify the vulnerability of a plaque.
However, analysis of the rf US signal, such as AR PSD estimation (the so-called VH method;
see Fig. 8-2) (23, 24, 25), wavelet analysis, and integrated backscatter (90) of the US rf signal
(unprocessed high-frequency backscattered signal received), enables plaque component
differentiation and hence renders such techniques useful for the characterization and
identification of vulnerable plaque (31,32,111). The VH method (23, 24, 25) has been FDA
approved and has been tested in vivo on coronary lesions of patients (26,29,112).
Another popular method is tissue characterization by elastography using the rf US signal with
compressions at different pressures (see Figs. 8-3 and 8-4). IVUS palpography has been
tested on patients (34,113), though it has yet to be approved for clinical use by the FDA. The
advantage of this software approach to detect vulnerable plaque is that it relies on existing
IVUS technology for image acquisition.
Targeted US contrast agents applicable to IV studies are also being investigated to highlight
specific plaque components such as endothelial adhesion molecules (114). IV-OCT has
resolution about an order of magnitude better than that of IVUS. This enables detection,
visualization, and characterization of coronary plaque components directly, including measuring
the thickness of the plaque caps (53, 54, 55). It cannot penetrate beyond 1-4 mm into the
vessel but may be adequate for thin-cap and lipid core detection.
IVMRI is being investigated for use of thin-cap vulnerable plaque diagnosis (83). Recent in vivo
clinical studies report its possible viability (71,85,115) for detecting and characterizing the
vulnerable plaque. Coronary arteries are deep-seated within the chest, small, and tortuous.
High-resolution noninvasive external coil MRI in vivo plaque imaging of the coronary arteries is
fraught with difficulties due to low signal-to-noise (SNR) and physiological motion (116, 117,
118). Fayad et al. used a fast double inversion recovery/fast spin echo sequence on a 1.5-T
MR system (118,119) with selective and nonselective inversion pulses that maximized the flow
suppression due to outflow. The in-plane spatial resolution was 0.5-0.78 mm and the slice
thickness was 3-5 mm. With this resolution, plaques with >40% stenosis on x-ray were seen as
3-5 mm in maximal wall thickness on MRI.
Other novel imaging techniques and modalities include thermal strain imaging with IVUS (120),
near-infrared spectroscopy, and thermography (31,32). Existing IVUS technologies are
increasingly being used for evaluation of the efficacy of various antiatherosclerotic therapies
(121). Combining the knowledge of vascular biology and MRI is improving our understanding of
atherothrombosis and acute coronary syndromes (122).
In the following sections we explore the physics of some of the existing and emerging
endovascular imaging techniques for visualizing and characterizing atherosclerotic plaque.
INTRAVASCULAR ULTRASOUND, VIRTUAL HISTOLOGY, AND

ULTRASOUND ELASTOGRAPHY
Overview of Intravascular Ultrasound Transducers and Array
Scanners
Diagnostic US is a real-time, nonionizing imaging modality. IVUS is the most widely accepted
modality for imaging atherosclerotic plaque and assessing the risk of rupture. Medical US
imaging involves transmitting high-frequency sound and receiving backscattered echoes from
soft tissue. Typically a small pulse (with a broadband of frequencies), at a center frequency of
1-80 MHz, is transmitted and the return echo gives the reflectance map of the tissue in the axial
direction. Higher center frequencies of the pulse afford better resolution. However, there is a
frequency-dependent attenuation effect, which makes higher-frequency US penetrate less in
tissue. In abdominal imaging, where depths of interests are up to 25-30 cm, the typical
frequencies used are 5-7 MHz. In breast imaging the depths are 6-10 cm and higher
frequencies such as 15 MHz can be used. For IVUS since the transducer is touching or close to
the tissue of interest and we are interested in only a few millimeters of penetration depth, we
can use much higher frequencies, of the order of 25-80 MHz.
Two fundamentally different devices exist for IVUS (13). One involves single piezoelectric
crystal transducers that are unfocused or have a fixed focus in three dimensions (1,5, 6, 7) and
the second has multi-element array transducers (2,3,8,9,12,13). The single-element
transducers can operate at very high frequencies (30-80 MHz) and, therefore, can afford high-
resolution imaging in their focal zone. For example, at 50 MHz a well-designed fixed-focus US
transducer should be able to image with a lateral resolution of 50-100 m (11). However, the
disadvantages are that these have fixed focus, where the resolution degrades away from the
focal zone, and are mechanically scanned, hence bulky, and require extensive
calibration procedures. Additionally, a challenge for US imaging in the 50- to 100-MHz range is
that the scattering from blood, as a function of increasing frequency, makes the interpretation of
US images difficult in vivo.
Circular array transducers operate at 20-30 MHz, with dynamic transmit/receive focus and no
moving parts. Dynamic focusing and scanning in the lateral direction can be done electronically
by delaying the transducer elements appropriately. For IV applications, arrays of transducer
elements are mounted on the surface of a highly flexible standard catheter. This allows them to
be integrated with an interventional device such as a stent or a balloon (8).
O'Donnell et al. (13) optimized the design of a side-viewing synthetic aperture IVUS catheter.
The smallness of the catheters (~1.2 mm) on which the transducer elements are mounted
(typically 64) and the power requirements limit beam-forming to synthetic aperture data capture
as opposed to classical phased array imaging. The frequencies of operation are limited to 20-
30 MHz.
Another categorization of IVUS devices (single elements or arrays) is that some are side-
viewing and others are forward-viewing or can operate in dual mode. Traditional side-viewing
IVUS devices provide a 360-degree cross-sectional image around the vessel lumen. For an
atheroma, a thrombus, or a plaque, the side-viewing catheter must remain in close contact with
a lesion. This presents a problem near severe stenoses. Forward-viewing transducers can
evaluate a lesion without crossing it (14, 15, 16,19,20). Some of the single-element designs are
mechanically scanned and might need extensive calibration and are bulky (14,16,19).
Wang et al. (20) devised and optimized a synthetic aperture array with side-viewing as well as
forward-viewing capabilities (Fig. 8-1). A dual-mode resonator is used to enable simultaneous
side viewing and forward viewing. The transducer element is cut appropriately such that when
excited by a broadband pulse, the transducer element will resonate at two frequencies. The
entire element resonates at a conventional (d33 mode) mode at a frequency determined by its
thickness, (e.g., 20 MHz) and one of the segments resonates at height extension resonance
(d13 mode) at a much lower frequency (e.g., 10 MHz). The higher-frequency mode can be
used for high-resolution side viewing, while the lower one can be used for forward viewing for
tracking and navigation. The side-viewing pulse echoes and the forward-viewing pulse echoes
are separated at three different levels. First, there is a frequency difference: side viewing is
typically at a center frequency of 20 MHz, with a bandwidth of 35% of the center frequency.
Second, the forward beam-former is completely uncorrelated with the side beam-former,
resulting in a 20-dB suppression of the forward-viewing receive echoes as seen by the side-
view beam-former, compared to its primary received signals at 20 MHz. Third, these two
modes propagate in orthogonal directions, further preventing interference.
Tissue Characterization: Virtual Histology with Intravascular

Ultrasound
As mentioned previously, IVUS is a useful tool to visualize arterial plaques. Highly automated
segmentation of plaque and arterial wall and a texture-based classification of the plaque into
soft plaque, hard plaque, or plaque-shadow have been shown with conventional IVUS data
(123). However, in general, IVUS images cannot characterize the vulnerable plaque into its
subcomponents.
In conventional IVUS, the high-frequency US backscattered data (usually referred to as the rf
data, at the carrier frequency) is envelope-detected and log-compressed. However, the raw rf
data prior to such preprocessing was found to provide valuable information regarding the
subcomponents of plaque tissue. Several analysis techniques of the rf data, such as frequency
domain analysis, wavelet analysis, and integrated back scatter, afford plaque characterization.
Spectral characteristics of the rf US data afford tissue characterization (23, 24, 25,124).
Spectrum analysis was done on the rf data for eight post-mortem coronary arteries by Watson
et al. (124). Imaging with a 30-MHz IVUS device, different feature points were picked from the
spectrum to characterize the plaques into three tissue groups: calcified plaque, lipid pool, and a
mixed fibrous category. The procedure was as follows. The rf data for each line around a
region of interest (ROI) were Fourier-transformed. Five adjacent spectral lines were averaged.
The power spectrum of a perfect reflector was adjusted from the average power spectrum, to
correct for the system response. Four feature points were chosen from the resulting normalized
power spectrum: the maximum power, the mean power, the spectral slope over a bandwidth of
18-35 MHz, and the intercept of the spectral slope with the zero-frequency axis. The
classification technique used is a minimum distance classifier. Each ROI is described by a
feature vector and the distance from the mean of each class cluster is calculated and the vector
is assigned to the class that it is nearest to. The Mahanlanobis distance, which normalizes the
data and takes into account the correlation between variables, is used. The class clusters were
formed using training sets, where the tissue classification is known. With the training and the
testing sets the same, the accuracy of classification was 86%. The result of classification into
these broad categories was 83% accurate using the leave-one-out strategy, where
classification is formed for each site in turn based on classes defined by all the other sites,
excluding the one site that is being classified. However, when categorized into seven clinical
subgroupsloose fibrous tissue, moderate fibrous tissue, dense fibrous tissue,
microclassification, calcified plaque, lipid/fibrous mixture, and homogeneous areas of lipid pool
the classification accuracy was only 54%.
Other ways to determine the PSD exist, AR methods being one of them. AR models have
typically provided better results for spectral analysis of US backscatter data, compared to the
more classical Fourier transform approach (23,24). In a study by Nair et al. (23), the AR
classification schemes outperformed the classical Fourier transform approaches. The
classification accuracies were 80%, 81%, 93%, and 86% for fibrous (collagen), fibrolipid,
calcium, and calcified necrosis for the test data (and even higher predictive accuracies for the
training set itself) for AR tree classification, while they were 67%, 77%, 83%, and 73% with the
Fourier approach. The order of the AR model chosen was 10, after testing several models. The
PSD is obtained as a function of the data and the AR model coefficients. These optimized AR
power spectra were normalized and then used to compute eight spectral features: maximum
power, corresponding frequency, minimum power, corresponding frequency, slope, y-intercept,
mid band fit, and integrated backscatter. The characterization was done using classification
tree modeling. At each juncture in a tree, unclassified data are separated based on one
variable (spectral parameter) that displays maximum separation of the plaque types. The
classification trees account for nonadditive behavior in data, considering intervariable
interactions that might not be known or taken into account with linear-regression techniques.
In a subsequent study (24), Nair et al. detailed the optimization of the order of the AR model.
This so-called regularization was incorporated to optimize the best SNR performance.
Different types of order optimizers were tried, including the Levinson-Durbin algorithm. In the
Levinson-Durbin algorithm, successively higher-order AR models are generated until the
reduction of the mean squared error reaches a plateau. The
best order is chosen where the mean squared error reaches a plateau. Other traditional
methods of estimating the order were compared with the Levinson-Durbin algorithm, such as
final prediction error, Akaike's information criteria, and minimum distance length. The
comparison had a mixed outcome. For sample lengths shorter than 64 samples, the Levinson-
Durbin algorithm proved to be a better technique for estimating the optimal order. However, for
a 16-sample ROI database, the conventional order optimizers might be more suitable.
This technique, VR, has FDA approval (31) and has been tested in vivo in human studies
(26,29). For example, using the virtual histology method, Fujii et al. (26) studied coronary
lesions with positive remodeling. Lesions were characterized into four types: fibrous, fibrofatty,
dense calcium, and necrotic core. The remodeling index was calculated as the lesion external
elastic membrane area divided by the proximal reference external elastic membrane area. The
mean lesion fibrofatty plaque area was significantly larger in lesions with positive remodeling
compared to those with intermediate/negative remodeling. The conclusion of the study was that
in vivo IVUS rf VH demonstrates that positive remodeling occurs in lesions with more fibrofatty
plaque.
Tissue Characterization: Elastography with Intravascular

Ultrasound
Tissue elastography and, more recently, Young's modulus imaging are other ways of
processing IVUS rf data to investigate the plaque composition, by trying to estimate the
mechanical properties of the subcomponents of the plaque. Elastography for plaque
vulnerability detection has been studied in vivo in patients as well as in animal models
(33,34,36, 37, 38,113,125).
Knowledge of mechanical property of the vessel wall and plaque can provide useful information
on vulnerability of a plaque, as illustrated in Figs. 8-3 and 8-4. In a plaque with a lipid core, the
stress due to arterial pulsatile motion might be too much to bear for a thin-cap plaque (126),
which might then become prone to rupture or thrombus development.
Strain imaging or elastograms for vulnerable plaque tissue classification were studied by de
Korte et al. (125,126). In one study, excised human femoral arteries were considered and the
tissue was compressed with pressures of 80 and 100 mm Hg (126). IVUS rf data at 30 MHz
were obtained before and after compression. Cross-correlation estimation of US backscatter
before and after compression is used to estimate the local strain. After IV imaging, the
specimens were stained to identify fibrous collagen, smooth muscle, and fatty tissue. It was
found that the strain in fatty tissue is higher than in fibrous material.
IVUS elastograms visualize the different radial strain patterns that emerge from compression of
the tissue. While the relative strain between different tissue types is informative, strain imaging
or elastograms do not capture an intrinsic property of the material. The strain will depend on
the unknown arterial stress distribution and these elastograms cannot be directly interpreted as
morphology or material characterization (127). Baldewsing et al. developed ways to take an
important step forward and capture the Young's modulus, using finite-element models of
vulnerable plaque along with elastograms (127, 128, 129).
To recover the Young's modulus image of different components of the vulnerable plaque, an
iterative reconstruction method is applied (127). First, a parametric finite-element model of a
thin-cap fibroatheroma was developed. Linear elastic, isotropic, and nearly incompressible
(Poisson's ratio, slightly 0.5) were chosen, as they were shown to be appropriate for
simulating the radial-strain elastograms obtained from IVUS (130). The parameters include the
geometry as well as the Young's modulus values for the thin-cap fibroatheroma parametric
finite-element model. From an initial guess of a Young's modulus map, this parametric finite-
element model is deformed. The resultant radial-strain field is compared to the actual radial-
strain elastograms obtained with the IVUS rf data. The Young's modulus image is updated and
simulated elastograms are calculated iteratively until the root mean squared error of the
simulated elastograms with the actual measured elastograms is minimized. Constrained
sequential quadratic programming was used to search for the minimum of the objective
function. The final Young's modulus map emerges as the Young's modulus image of the plaque.
This method successfully reconstructed the Young's modulus images from elastograms
measured from in vitro human coronary plaque (127). It was also applied in vivo to a patient.
OPTICAL COHERENCE TOMOGRAPHY

Overview of the Optical Coherence Tomography System
OCT employs low-coherence interference of light and produces high-resolution cross-sectional
images of tissue. The coherence optics imaging principles are similar to those of pulse-echo US
in that a light pulse is emitted and the delayed backscattered echo is measured. The advantage
of OCT is that its resolution can be 10-15 m, an order of magnitude higher than IVUS, IVMRI,
or computed tomography (CT) (45). The penetration of OCT varies. For imaging the
transparent layers in the eye, depths >2 cm can be achieved. For skin and other highly
scattering tissue, OCT can image about 1-4 mm beneath the surface.
Figure 8-8 shows a schematic of an OCT system. An optical beam, typically from a broadband
(a short-pulse) light source (such as superluminiscent LEDs, or SLEDs), is split in two with a
beam-splitter. The light source needs to have a high irradiance. One arm of the beam is sent to
a mirror to be returned as a reference signal, and the other into the sample to be imaged. The
sample beam and the reference signal are mixed together to get the interference signal. The
relatively low-coherence length
of the SLEDs compared to monochromatic lasers ensures resolution in the micrometer range.
The coherence length L of a source is given by
FIGURE 8-8. Component block diagram of an OCT system. (Reprinted with permission of
IEEE from Schmitt JM. Optical coherence tomography [OCT]: a review. IEEE J Select
Topics Quantum Electron. 1999;5[4]:1205-1215, IEEE.)
where c is the velocity of light. Note that the time-frequency and wavelength in space are
related by the well-known relationship = c/. Taking the derivative, we get the relation
between the absolute bandwidths in frequency and space as = c/2. Approximating by
assuming the center wavelength, Eq. 8-1b follows from Eq. 8-1a.
In OCT, the center wavelengths are typically 800-1,300 nm, and the spread in the wavelengths
is 75-100 nm. Hence, the beams transmitted into the media have emission in the near-infrared
range, with a short temporal coherence length (a short pulse). Two-dimensional cross-sectional
images are produced by multiple axial scans in the lateral direction. The optical transfer function
of the scanning and focusing beam affects the resolution. The point-spread function is
approximately separable in the lateral and axial directions (41). Hence, as in the case of
phased-array medical US systems, the axial resolution is determined by the spatial extent of
the source pulse and the lateral resolution is determined by the optical system point-spread
function.
Visualization and Characterization of Plaques

OCT has been used (and often compared with standard IVUS, though not VH or tissue
elastograms) ex vivo, for in vivo patient studies for plaque visualization (52), and, more recently,
for tissue chacterization (51,53, 54, 55). Due to its high resolution, it is the only imaging
technique so far that is capable of precisely measuring the plaque thickness directly (54).
Comparison of OCT with histology suggested that lipid-rich and fibrous plaques have distinct
OCT characteristics (52). In the same study, a total of 17 image pairs of IVUS and OCT were
obtained from 10 patients. Axial resolutions measured 13 3 m in OCT versus 98 19 m
with IVUS. All fibrous plaques, macrocalcifications and echo-lucent regions identified in IVUS
were also identified in corresponding OCT images. Intimal hyperplasia and echo-lucent regions
that may correspond to lipid pools were identified more often in OCT than in IVUS images.
In vivo characterization of coronary atherosclerotic plaque using OCT proved successful as
well. Jang et al. studied different categories of patients undergoing cardiac catheterization:
acute myocardial infarction (AMI), acute coronary syndrome (ACS), and stable angina pectoris
(SAP). Two observers independently analyzed the images. A total of 57 patients were
analyzed: 20 with AMI, 20 with ACS, and 17 with SAP. In AMI, ACS, and SAD groups, lipid-rich
plaques were observed in 90%, 75%, and 59% respectively, with a median value of the
minimum thickness of the fibrous cap of 47.0, 53.8, and 102.6 m, respectively. The
occurrence of TCFA was 72%, 50%, and 20% in the AMI, ACS, and SAP groups, respectively.
Van der Meer et al. measured local light attenuation with OCT to characterize the different
plaque components quantitatively (54,55). Though applied to carotid arteries, the detected
difference in the attenuation coefficient of incipient fat deposits compared to that of other
tissues indicates that this technique might enhance the diagnostic capabilities of OCT (54).
INTRAVASCULAR MAGNETIC RESONANCE IMAGING

Overview
The two IV imaging modalities discussed so far have their limitations. IVUS suffers from limited
resolution and OCT suffers from limited penetration. Both have high speckle noise that affects
detection and contrast. Several investigators have shown the potential of MRI to detect and
distinguish different types and components of plaque and thrombi (71,74,75,83,85,86,131).
MRI can distinguish among the three layers of the vessel wall and detect atherosclerotic plaque
(74, 75, 76). On an isolated vessel removed at the time of carotid endarterectomy, Yuan et al.
(62) could distinguish foam cells, fibrous plaque, organized thrombi, new thrombi, areas of
loose necrosis, and calcium. Employing a fast spin echo MRI at 1.5-T main field with various
T1- and T2-weighted pulse sequences, they were able to distinguish among the different
tissues of interest.
High-resolution imaging is necessary for distinguishing tissue types in arterial plaque. Martin et
al. (60) performed high-resolution MRI with dedicated surface coils to show that MR images
correlate reliably with tissue types. However, there is a fundamental limitation with MRI in that
the voxel size is in general proportional to the SNR. Hence, in general, the higher the resolution
of the surface coil imaging system, the greater the noise (lower SNR).
High-resolution imaging of atherosclerotic plaques is optimally achieved by the receiver placed
close to the target vessel (64). Using IVMRI typically improves the SNR by 2-10 times surface
coils (132). The first IVMRI was devised by Kantor et al. in 1984 (73). Since then various
IVMRI coils and antennas have been invented, optimized, and tested (57, 58, 59,61,64,65,67,
68, 69,73,77,82,84).
IVMRI catheter probes can be broadly divided into two groups. In one, a small coil(s) or a
conductor is placed on a catheter and inserted into the blood vessel to act mainly as a receiver.
The receiver operates inside a standard MRI clinical machine to receive the transverse
magnetic fields induced by various pulse-sequencing protocols. The receive coil or conductor
has higher SNR characteristics, being closer to the blood vessel than standard or surface coils.
Most of the applications described here belong to this category (57, 58, 59,61,64,65,67, 68,
69,73,77). However, recently a radically different approach has been applied: it consists of a
self-contained IVMRI catheter probe that functions independently, without requiring an external
MRI system (82, 83, 84). They can be used directly in the catheter lab. These self-contained
MRI units have tiny magnets to generate the static magnetic field as well as the gradient fields,
and a rf coil that works for both signal transmission and reception.
Larose et al. (133) performed the first in vivo study with this system on patients. The study first
validated IVMRI images against histopathology of human atherosclerotic arteries ex vivo. Then
these investigators compared the IVMRI and IVUS of iliac arteries of 25 human subjects in vivo.
The IVMRI coil used in the study was a 100-cm, flexible, loopless wire with a 7-cm-long distal
receiver region. The MRI protocol (T1-, T2-weighted pulse sequences) followed methods used
by Atalar et al. (64) and Worthley et al. (70). IVMRI could delineate the inner and outer
boundaries of the plaque including cases with calcification, which were difficult to interpret with
IVUS. IVMRI also showed the heterogeneity of the plaque, which was not visible on IVUS. The
level of intra- and interobserver agreement in interpretation was higher for IVMRI compared
with IVUS.
In a second study, Wilensky et al. (85) report the initiation of clinical studies with self-contained
IVMRI unit in patients undergoing cardiac catheterization for diagnosis or intervention. They
were able to evaluate the plaque lipid content safely with the self-contained device.
Receive Coils and Conductors

Description
In 1984 Kantor et al. (73) designed a catheter coil to improve the SNR of 31P spectroscopy of
the canine heart. Since then, several independent groups such as Hurst et al. (57), Martin et al.
(58,59), Kandarpa et al. (61), Atalar et al., Ocali et al. (64,65), Hillenbrand et al. (67,68), and
Farrar et al. (69) have developed catheter receive coils or antennas and used them for imaging
ex vivo or in animals in vivo.
The primary aim behind the IVMRI designs is to improve the SNR with respect to conventional
MRI when imaging blood vessels. Hence obtaining sensitivity maps of each of the designs is an
important task. The primary concerns in designing these probes are the inhomogeneity of the
SNR, due to signal and noise inhomogeneity, and the additional challenges added due to
physiologic motion.
The rf fields patterns of these tiny catheter probes are different from those in conventional MRI
in that the field is highly inhomogeneous, resulting in nonuniform SNR or sensitivity maps. Hurst
et al. (57) characterized the sensitivity function of several different probe designs such as the
opposed-solenoid coil, one-loop coil, and four-wire birdcage coil, by applying the Biot-Savart
law. Figure 8-9 shows schematic diagrams of these various designs.
The opposed-solenoid probe, which involves two coils face to face with currents flowing in
opposition, was found to perform the best in terms of presenting a homogeneous field in a thin
region between the two coils inducing opposing magnetic fields. Crottet et al. (77) measured
the spatial variation of the sensitivity and the rf-field strength point by point using a small water
sample as a voxel, for an opposed-solenoid catheter coil. The study showed the reciprocity
relation at work. However, as mentioned, the coil designs had practical issues of bulk,
mechanical rigidity, and motion susceptibility.
Kandarpa et al. (61) designed single-loop, multiturn rf coils with 100 m in-plane resolution and
tested them on human arterial specimens, showing a close correspondence to histology. Hurst
et al. (57) used opposed-solenoid coils to image blood vessels of dogs in vivo, but the pulsatile
motion of the blood resulted in blurry images. Martin et al. (59) solved the coil motion problem
in an innovative way by introducing a mechanical extension like a bullet and obtained good in
vivo images in pigs. Nevertheless, this design may obstruct blood flow. One issue with
opposed-solenoid coils is that the sensitivity is maximized when the midplane between the two
coils is aligned perpendicular to the axis of the main magnetic field Bo. However, Hua et al. (56)
showed that the sensitivity is relatively stable up to 45-degree inclination. Hillenbrand et al. (67)
built a dual-purpose tracking and IVMRI imaging coil using an opposed-solenoid phased-array
coil. The two solenoid coils can operate independently and are wound in opposing directions
and connected to separate receive channels, mounted on an angiographic catheter. The two
elements can then be used independently to track or together to do high-resolution IVMRI. This
coil was tested in vitro, in situ, and in vivo on animal models (pigs) with a 1.5-T clinical MRI
scanner.
Some IVMRI coils have other practical limitations, being too rigid and/or big to be inserted into
very small, diseased, tortuous arteries. The coil diameter must match the vessel inner diameter
for optimal imaging, but it is important that blood flow is not obstructed. Also, when the coil is
not oriented parallel to the main applied MRI magnetic field, SNR loss occurs. A two-conductor
flexible catheter receiver coil design by Atalar et al. (64) was used in small blood vessels of
rabbits in vivo. This was designed by short-circuiting one end of a two-conductor transmission
line, which allows smaller size and greater flexibility. Atalar et al. (64) showed that the
inhomogeneity of the signal can be precalculated and compensated for different configurations
of the catheter in vivo. Note that this compensates for the signal inhomogeneity but can
potentially increase the noise. Both the signal and the noise received by these loop coils are
very low. The cable connecting the coil to the matching and tuning electronic circuit can
contribute significantly to the noise. Hence the electronics have to be small (of the order of
millimeters) and close to the catheter coils, inside the blood vessels. Some of these issues
were addressed by Ocali and Atalar (65), who used a single loopless conductor as a receiver
antenna to measure the magnetic field. The receiver is a single thin conductor creating a dipole.
The electromagnetic properties of the thin single conductor are virtually independent of its
diameter, unlike coils that incorporate a loop (65). The signal power (as well as the noise)
pickup of the antenna is high. The noise due to electronic cable connections is low in
comparison, and hence the electronics can be placed outside the blood vessels.
FIGURE 8-9. Different coil designs. A: Coordinate system of vessel, coil former, and Bo.
Conductor winding pattern of (B) opposed solenoids (OS), (C) rectangular loop, (D) four-
wire birdcage, (E) four-wire mulipole, and (F) four-wire center return. (Used with
permission of Wiley-Liss, Inc., a subsidiary of John-Wiley & Sons, Inc., from Hurst GC,
Hua JM, Duerk JL, et al. Intravascular [catheter] NMR receiver probepreliminary design
analysis and application to canine iliofemoral imaging. Magnet Reson Med.
1992;24[2]:343-357.)
FIGURE 8-10. A: Concept of an expandable imaging coil (Kandarpa K, Jakab P, Brigham
and Women's Hospital, 1994, unpublished). Shows the cross section once the coil is
expanded inside a blood vessel; the thick black lines denote the expandable sections. B:
Longitudinal schematic view of the expandable coil. C: In vitro flow model of human
abdominal aorta with physiological flow conditions. Dark interior represents the aortic
lumen. Outside the lumen the coil is imaging a slice of fatty beef wrapped around the tube
(T1W). This design matches the coil diameter to the vessel without obstructing flow
through the lumen.
One of the drawbacks of a single-conductor catheter antenna is that it may stay within the
middle of the lumen, while the area of interest is the vessel wall, at a distance at which the
sensitivity of the probe is much lower. In unpublished (1994) work, Kandarpa et al. proposed a
design where the catheter can be expanded once inside the blood vessels, so that the receiver
elements are closer to the wall of the blood vessels. Figure 8-10 illustrates the design and an
image of a phantom.
Farrar et al. (69) proposed the cylindrical meanderline coil, as illustrated in Fig. 8-11. This
cylindrical meanderline coil was tested on phantoms and human endarterectomy surgical
specimens. These coils can be used in rf transmit/receive mode. Farrar et al. (69) mentioned
that future designs would include tuning capacitors to reduce asymmetry in the electromagnetic
field around the coil and smaller-diameter and flexible shapepersistent material that would allow
the coil to be expanded to match the blood vessel diameter. The primary advantage of the
designs in Figs. 8-10 and 8-11 over some of the other coil/conductor designs is that the
sensitive region of the coil is matched to the cylindrical geometry and diameter of the blood
vessels. Thus the dynamic range is not taken up by intense blood signals but is tuned directly to
the lower signals from the artery walls and atherosclerotic plaque. Another innovative design is
described by Quick et al. (78). They use a vascular stent itself as a rf antenna for IVMRI.
Three principles were tested. First, the stent was used as a loop antenna; second, it was
employed in an electric dipole configuration; and, finally, the stent was used in a hybrid
configuration as a coaxial line antenna. The three configurations led to different signal-to-noise
characteristics and the second two designs proved practicable for in vitro and in vivo
experiments on sheep. The co-axial hybrid design can be used for actual monitoring and stent
deployment, and the electric dipole design permits high-resolution imaging of the vessel wall
and other structures.
FIGURE 8-11. Comparison of a planar and cylindrical meanderline coil. The sensitivity
drops off exponentially from the planar coil surface and by a power law for the cylindrical
coil, external to its surface. The thickness of the sensitive volume (or depth of view) is of
the order of the conductor spacing. (Reprinted with permission of Wiley-Liss, Inc., a
subsidiary of John-Wiley & Sons, Inc., from Farrar CT, Wedeen VJ, Ackerman JL.
Cylindrical meanderline radiofrequency coil for intravascular magnetic resonance studies of
atherosclerotic plaque. Magnet Reson Med. 2005;53[1]:226-230.)
Magnetic Resonance Imaging Protocols for Intravascular

Magnetic Resonance Imaging Receive Designs
The probe designs discussed so far work in conjunction with a standard MRI machine. The
transverse magnetization obtained by different pulse-sequence protocols is received by the
internal coils and conductors near the blood vessels. A comprehensive study by Hillenbrand et
al. (68) investigated 10 protocols to observe their effects on the IVMRI. The protocols studied
include spin-echo-echo planar imaging (SE-EPI), segmented EPI, half-Fourier single-shot turbo
spin-echo (HASTE), fast imaging with steady-state free precession (TrueFISP), turbo spin-echo
(TSE), and spin-echo acquisition schemes. The IVMRI coil used was a custom-made, single-
channel, opposed-solenoid coil. Experiments were conducted on healthy pigs. The images were
analyzed by six experts with respect to wall conspicuity, walltolumen tissue contrast, visible
layers of arterial wall, anticipated clinical usefulness, and overall image quality. In almost all the
protocols the vessel wall was delineated. The fast techniques reduced motion artifacts due to
device and physiological motion. The best contrast between wall and surrounding tissue was
provided by a HASTE protocol. Anatomic layers of the vessel wall were best depicted on dark-
blood T2-weighted TSE. Overall, TrueFISP ranked the highest on all the remaining criteria.
The Self-Contained Intravascular Magnetic Resonance

Imaging Probe
Zur (82) and Blank et al. (84) describe the theory and development of a self-contained IVMRI
catheter probe that is capable of arterial vessel wall imaging, without external magnetic fields
or coils (Fig. 8-12). Schneiderman et al. (83) and Wilensky (85) describe the clinical use of the
probe to identify plaques and their components in ex vivo specimens and in vivo patients,
respectively.
The catheter tip is 1.73 mm in diameter. For such a smalldiameter probe, from the energy-
efficiency point of view, a permanent magnet (and not a miniature electromagnet), of about
1.36-T remanence magnetic field, is used. Two magnets are mounted on the catheter with a rf
coil mounted in the middle as shown in Fig. 8-12. The static B0 field is predominantly in the z-
direction, while the rf field acts in a plane perpendicular to B0. A sector-shaped area looking
sideways into the artery wall is the volume of interest (83,84).
For such a small magnet, the field pattern is highly inhomogeneous and a typical value of the Bo
field is 0.2 T (84). The
gradient fields that result from such small configurations are very high, 150-200 T/m, and may
be controlled to some extent by changing the angle of magnetization and the gap length
between the two magnets (84). Due to its small size and radial falloff of its static and rf
magnetic fields, the volume of interest should be within 400 m. Typical vessel areas of interest
are within 250-300 m of the edge of the probe, which is stabilized with a balloon. A repeated
Carr-Purcell-Meiboom-Gill (CPMG) protocol is used. The nuclear-spin diffusion and the usual
relaxations are dominant effects. When the separation between the 90-degree and the 180-
degree pulse in CPMG is large, the echo decay is dominated by the diffusion. When the
separation is small, T2 relaxation effects are dominant (84). The SNR is calculated exactly by
Zur (82) and approximately by Blank et al. (84). The exact calculation involves solving the Bloch
equation on a grid of points taking into account relaxation as well as spin diffusion (82). Zur's
theory (82) is validated by actual measurements by Blank et al. (84) and can then be used for
optimizing the self-contained IVMRI probes in clinical use.
FIGURE 8-12. Self-contained IVMRI probe. A: Drawing of the miniature self-contained
insideout probe designed by Blank et al. (84). The diameter is 1.73 mm; the height
(defined by magnets), 10 mm. The resultant static field is predominantly along the z-axis,
and the rf field is mainly along the x-axis in the measurement volume (just in front of the rf
coil). B: Photograph of the probe inside a catheter. C: A different view of the probe
components showing the direction of magnetization. D: A cartoon showing the method of
signal acquisition with the probe inside the blood vessel. (Reprinted with permission of
Wiley-Liss, Inc., a subsidiary of John-Wiley & Sons, Inc., from Blank A, Alexandrowicz G,
Muchnik L, et al. Miniature self-contained intravascular magnetic resonance [IVMI] probe
for clinical applications. Magnet Reson Med. 2005;54[1]:105-112.) (See the color insert.)
Scheiderman et al. (83), applied the self-contained IVMRI clinically. The lipid-rich and fibrotic-
rich areas of the atherosclerotic plaque were differentiated on the basis of differential water
diffusion. This has the potential for early detection of thin-cap fibroatheromas. The study was
done on ex vivo human aortas and in situ coronary arteries. The imaging volume was 60
degrees (sector shaped), with a depth of view 250 m (slice thickness, 2 mm). For imaging
beyond 300 m, longer averaging times (>90 seconds) are required for improving the SNR,
which might be a potential limitation for clinical use.
Wilensky et al. (85) reported clinical studies with the IVMRI unit in patients with intermediate
lesions performed during coronary angiographic assessment or concomitant percutaneous
interventions. The group is looking to using the IVMRI unit combined with molecular and
targeted imaging to locate the presence of increased concentrations of macrophages and/or
thrombi.
CONCLUSION
Of the three modalities discussed here, OCT has the best resolution (~10 m) and can detect
even thin-cap plaque in vivo without postprocessing. The penetration is limited to 1-4 mm but
this might be adequate for thin-cap fibroatheroma imaging.
IVUS has a resolution of ~0.1 mm but can penetrate about a centimeter. Intelligent processing
methods such as AR spectral analysis and tissue elastography have made characterization of
the vulnerable plaque viable. This modality is likely to persist for a long time, as clinicians are
used to IVUS imaging, and additional software processing alone leads to robust tissue
characterization. Moreover, IVUS can be used to guide local drug/agent delivery for therapy.
IVMRI is rapidly developing as a viable imaging option, but more clinical studies are needed to
demonstrate its robustness for tissue characterization. It has a better resolution than IVUS but
worse than IV-OCT. The penetration depth is between those of the other two modalities. The
contrast resolution with IVMRI is better than with either IVUS or OCT. When noninvasive
techniques such as high-resolution MRI reach an adequate SNR and resolution, they may
enable routine clinical in vivo characterization of plaque.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 9 - Carotid Artery
Revascularization
Chapter 9
Carotid Artery Revascularization
Ajay K. Wakhloo
Stroke is the third leading cause of death in the United States; more than 150,000 deaths
annually are attributed to stroke and it is also the number one cause of neurological disability
(1, 2, 3). The most common etiology of stroke is ischemia, caused by occlusion of an
intracranial blood vessel. Of the 700,000 to 750,000 new strokes per year, 83% of these are
secondary to ischemic events (4, 5, 6). Acute ischemic stroke results in death within 30 days
for 7.6% of victims (5,7). Stenosis of the extracranial internal carotid artery (ICA) resulting from
atherosclerotic disease is estimated to be causative in more than 20% to 30% of cases (7).
Although the precise prevalence is unknown, large studies estimate that 5% of people in their
sixties and 10% of people >80 years old have atherosclerotic occlusive disease of the carotid
artery (8); because of aging of the population, the number of patients with symptomatic carotid
artery disease is growing (9). It becomes the second most common cause of death by 85
years of age (10).
Stroke has been subdivided pathologically into ischemic and hemorrhagic forms. A major cause
for a brain infarct is an embolic event. In many patients, a source is readily apparent in the
heart or the diseased carotid artery. Cardiac causes of embolic ischemia include mitral valve
disease, rheumatic heart disease, cardiac arrhythmia, infective endocarditis, atrial myxoma,
and mural thrombus. Atrial septal defects and patent foramen ovale can cause paradoxical
emboli by enabling the passage of venous embolus to the arterial circulation. An ulcerated
plaque in the carotid artery may be another major source of emboli. Less common causes of
stroke include vasospasm after subarachnoid hemorrhage, fibromuscular dysplasia, most
commonly if located in the intracranial carotid artery segment, atherosclerosis of the aortic arch
(AAA disease), atherosclerosis of the intracranial arteries, inflammatory arterial disorders such
as systemic lupus erythematosus, polyarteritis, granulomatous angitis, and meningovascular
syphilis. Also, patients presenting with AIDS are at an increased risk for a stroke.
Hematological disorders as a cause of an ischemic event include polycythemia, sickle cell
disease, and hyperviscosity syndromes. Perioperative strokes are, in a majority of cases,
ischemic and embolic (11, 12, 13). Hemorrhagic stroke can be caused by vascular anomalies,
for example, ruptured aneurysm, cavernoma, dural arteriovenous fistula, and arteriovenous
malformation. Further etiologies for a hemorrhagic stroke can be arterial and venous
hypertension, hematological bleeding disorders, for example, leukemia, thrombocytopenia,
hemophilia, or disseminated intravascular coagulation, anticoagulant therapy, liver disease,
cerebral amyloid angiopathy, and brain tumors (7).
In 1951, Miller Fisher first described the symptoms and the pathologic substrate of carotid
artery atherosclerotic occlusive disease (14). The majority of patients who have carotid artery
stenosis presents with a stroke. Other patients present symptoms consistent with a transient
ischemic attack (TIA). Some of these symptoms consist of ipsilateral amaurosis fugax,
contralateral sensory or motor dysfunction limited to one side of the body, aphasia,
contralateral homonymous hemianopia, or combinations thereof.
Several risk factors play a role in the development of carotid artery stenosis. There are
nonmodifiable factors including age, male gender, race, genetics, and family history. The
disease is also more common in some ethnicities like Hispanics and African Americans.
Modifiable risk factors include smoking, hyperlipidemia, sedentary lifestyle, increased body
mass index, oral contraceptive use, alcohol and substance abuse, diabetes mellitus,
hypertension, prior TIA or stroke, elevated homocysteine levels, elevated anticardiolipin
antibodies, presence of a carotid bruit, cardiac disease, increased fibrinogen, and low serum
folate.
Carotid Artery Anatomy

The right common carotid artery (CCA) arises from the brachiocephalic trunk, the first and
largest branch of the aortic arch, at the level of the right sternoclavicular joint. The left CCA, the
second branch of the aortic arch, arises posterior to the manubrium, slightly posterior and to
the left of the brachiocephalic trunk. It ascends anterior to the left subclavian artery and is at
first anterior to the trachea and then to its left. It enters the neck by passing posterior to the left
sternoclavicular joint. The CCA ascends in the carotid triangle of the neck, bounded by the
superior belly of the omohyoid, the posterior belly of the digastric, and the anterior border of
the sternocleidomastoid muscles. This is where its pulse can be auscultated or palpated by
compressing it lightly against the transverse process of the cervical vertebrae. At the level of
the superior border of the thyroid cartilage, the CCA divides into the internal and external
carotid arteries. Found at this site are the carotid sinus and the carotid body. The carotid sinus
is a slight dilation of proximal part of the ICA, is innervated by the glossopharyngeal nerve
through the carotid sinus nerve, as well as by the vagus nerve, and acts as a baroreceptor that
reacts to changes in arterial blood pressure. The carotid body is a small, reddishbrown ovoid
mass of tissue that lies on the medial side of the bifurcation that is innervated by the
glossopharyngeal and vagus nerves also and serves as a chemoreceptor that monitors the level
of oxygen in the blood. In the carotid sheath, which is a thickly matted fascia condensation on
each side of the neck, the carotid artery is accompanied by the internal jugular vein medially
and the vagus nerve posteriorly. The external carotid artery gives branches that supply the face
and neck. The ICA continues ascending in the neck and enters the cranial cavity, passing
across the cartilage of the foramen lacerum.
PATHOPHYSIOLOGY OF ATHEROSCLEROSIS
Atherosclerosis is a general term used for all structural changes that result in hardening of the
arterial walls, sometimes called atherosclerotic plaque. Stroke, due to atherosclerosis of the
extracranial carotid arteries, is caused by a combination of factors involving the blood vessels,
the clotting system, and hemodynamics. This interaction explains the mechanism of ischemic
stroke in patients with carotid atherosclerosis, which may be due to artery-to-artery embolism
or, rarely, to low cerebral blood flow due to a high-grade stenosis. Patients with symptomatic
carotid disease usually have heterogeneous plaques that are the source of shed emboli. The
degree of carotid artery stenosis alone may not enable an adequate prediction of which
patients will suffer strokes. Extensive studies of plaque characteristics have revealed a
correlation between the histological features of a plaque and its potential to cause
thromboembolic events. These characteristics have been studied mainly to correlate ultrasonic
findings, but research is ongoing to develop less invasive techniques, such as magnetic
resonance imaging and molecular imaging, which try to differentiate between a stable and an
unstable or vulnerable plaque.
Carotid plaques have a variety of characteristics that are distinguished as either homogeneous
or heterogeneous plaques (15). Homogeneous plaques are stable, with deposition of fatty
streaks and fibrous tissues. These plaques rarely have evidence of hemorrhage or ulcerations.
On the other hand, heterogeneous plaques are unstable, with histological characteristics of
lipid-laden macrophages, monocytes, leukocytes, necrotic debris, cholesterol crystals, and
calcifications. Heterogeneous plaques have been shown to be an independent risk factor for
stroke regardless of the degree of stenosis. Plaques may be hard with calcium, lipid, and
cholesterol accumulations within the vessel wall. The cholesterol-rich, slightly raised fatty streak
becomes a fibrous plaque. As the atherosclerotic plaque develops, the elicited biologic
response is an attempt to cover the plaque with a fibrous cap. The complicated plaque may
undergo rupture, intraplaque hemorrhage, extensive necrosis, calcification, and subsequent
thrombosis. Infiltration of the fibrous cap by foam cells may also contribute to the rupture
following which underlying debris is released into the circulation. Restabilization of the ruptured
plaque includes a normal cascade of wound healing responses leading to heterogeneous
structure. Diffuse intimal thickening is growth of the intima through the migration of medial
smooth muscle cells into the subendothelial space through the fenestrations of the internal
elastic lamina, associated with increasing amounts of elastic fibers, collagen, and
glycosaminoglycans.
In addition to a reduction in vessel diameter induced by the enlarging plaque, thrombus can
become superimposed on the plaque, which will further increase the degree of stenosis. Thus,
the mechanism of stroke may be embolism of the thrombotic material. The affected artery can
be involved in a symmetric or asymmetric manner. Carotid atherosclerosis is usually most
severe within 2 cm of the bifurcation of the CCA and predominantly involves the posterior wall
of the vessel. The plaque encroaches on the lumen of the ICA and often extends caudally into
the CCA; however, it may extend apically into the carotid canal. An hourglass configuration to
the stenosis typically develops with time.
HEMODYNAMICS OF CAROTID ARTERY STENOSIS

Hemodynamic mechanisms for the initiation and progression of carotid bifurcation
atherosclerotic occlusive disease have been extensively researched during the past few
decades. Attention has focused on the carotid bulb, or sinus, where most atherosclerotic
plaques are found. The unique geometry of the carotid bifurcation governs the local
hemodynamics, which have been implicated in carotid artery wall heterogeneity. The carotid
bulb, or sinus, appears to host a unique blood flow environment and is thought to play a role in
local blood flow disturbances that lead to endothelial cell damage and subsequent plaque
formation. The proximal segment of the ICA, where flow is separated, is the most common site
for the development of plaque (16, 17, 18). Many factors, such as blood flow velocity, mural
tensile stress, turbulence, and arterial wall shear stress (19, 20, 21, 22), have been proposed
as causative factors in the initiation of atheroma. Wall shear stress, in particular, has been
explored and consequently implicated as an atherogenic factor by many investigators
(16,17,20). Initial hypotheses involving wall shear stress contended that atheroma formation at
sites with low wall shear was due to a decreased efflux of cholesterol (19). Other studies (20)
have suggested that atheroma formation occurs at sites with high wall shear stress due to
damage caused to the endothelium. Vascular zones susceptible to plaque formation have been
found to experience a combination of low and oscillating shear stresses, whereas zones with
high wall shear are relatively free of disease.
Endothelial Reaction to Flow

The endothelial cell monolayer serves as the communicating medium between the flowing blood
and the arterial wall. It provides a protective barrier to arterial damage; disruption to this barrier
in a given hemodynamic environment could contribute to atherogenesis (23). Focal ulcerations
of the lumen or removal of the endothelial cells by shear forces do not evoke initiation of
atherosclerotic disease (24). However, vasoactive and toxic substances produce modifications
of endothelial reactivity and metabolism (25). The dynamic response of endothelial cells
includes changes in permeability; oxidative modification of low-density lipoproteins; and release
of chemoattractants, mitogens, and growth factors that produce alterations in the smooth
muscle cells of the media (25).
Poststenotic Dilatation and Narrowing

Poststenotic dilatation (PSD) is frequently observed in carotid stenosis and was described as
early as 1842 (26). PSD is characterized by a decrease in the density of smooth muscle cells
and elastin content as well as an increase in collagen and the presence of collagenase. Nitric
oxide (NO) seems to be essential for the mediation of PSD and an increased level of
endothelial nitric oxide synthase (eNOS) mRNA and protein is found (27). Poststenotic
narrowing of the ICA is seen frequently on angiograms and is considered to be a consequence
of the hemodynamics associated with a vascular constriction. It has been proposed that this
hemodynamic effect could produce systolic wall collapse distal to the stenosis (28, 29, 30).
Other possible mechanisms of poststenotic reduction in arterial diameter may be related to an
endothelial dysfunction interfering with NO production. Intimal thickening may explain the
observed diameter reduction distal to a stenosis. Poststenotic collapse may be a possible
mechanism for plaque rupture with an artery-to artery emboli (31,32). However, a recent report
in a large patient sample has shown that the ischemic stroke rate was statistically lower in
cases where poststenotic narrowing was observed compared to cases without it (33). The 5-
year risk of ipsilateral carotid artery ischemic stroke in patients with a stenosis between 70%
and 99% treated medically, and having poststenotic narrowing, was 8%. The rate for patients
who did not show poststenotic narrowing was 25%. These data show
that poststenotic narrowing is associated with a lower risk of stroke.
IMAGING OF CAROTID ARTERY DISEASE

Successful treatment of carotid artery stenosis and prevention of subsequent ischemic strokes
in both asymptomatic and symptomatic patients have made the development of new cost-
effective and safe methods of assessing carotid lesions more important. Documentation of very
specific degrees of carotid stenosis has made the use of accurate measuring methods
essential.
For decades, cerebral angiography has been the gold standard for the evaluation of
cerebrovascular disease. In the last decade, duplex scanning has emerged as the preferred
non-invasive method of evaluating these patients. The question is whether duplex scanning
alone, or in combination with other noninvasive imaging methods such as computed
tomographic angiography (CTA) and magnetic resonance (MR) angiography (MRA), is a
reliable and safe way to evaluate these lesions and to accurately select patients for whom
surgical intervention is indicated. In this section, we review the principal preoperative imaging
modalities for the carotid artery and discuss the sufficiency of noninvasive testing for patients
with cerebrovascular disease.
Plaque Evaluation
A measurement of the intima and media of the artery can provide the examiner with a better
understanding of the vascular disease. The normal value for the intima media thickness is <0.8
mm. A value >1.1 mm has been denoted abnormal, and serial measurements have been used
in the past to evaluate the vessel response to various medical treatments. Plaque
characteristics have been studied not only to elucidate the cause of the disease but also in an
effort to correlate them with either intravascular or perivascular findings at ultrasonography
(US). No universal system exists but usually the examiner evaluates the surface characteristics,
echogenicity, density, and texture. Surface irregularities or plaque ulceration has also been
shown to be a risk factor for thromboembolic events. These ulcerated plaques consist of soft,
gelatinous clots that contain platelets, fibrin, white blood cells, and red blood cells. Plaques that
are more likely to be related to stroke have a low echogenicity on US. This corresponds to a
weak reflection of US and echolucency due to the lipid and hemorrhage content of the plaque.
These plaques are soft and friable. Plaque texture is either heterogeneous or homogeneous.
Heterogeneous plaques are seen as complex structures with at least one area of sonolucency
that could represent an area of focal hemorrhage. They can present ulcerations and some of
them can present irregular calcifications also. On the other hand, homogeneous plaques are
smooth and resemble the surrounding tissues (15).
Carotid Artery Stenosis Quantification

In the area of maximal stenosis, the blood flow velocity increases. It is the peak systolic blood
flow velocity through this area that is used to analyze the severity of the stenosis. In this area,
the flow pattern is usually not disrupted. One to two centimeters distal to the stenosis, the flow
is disrupted; it spreads out, causing disturbed flow with broadening of the Doppler spectrum.
Numerous velocity criteria are used when grading the stenosis of the ICA. The peak systolic
velocity (PSV), the end diastolic velocity (EDV), and the ratio of PSV of the ICA to PSV of the
CCA are assessed. If a discrepancy between these parameters is found, the interpreter can
add the diagnostic value of the color Doppler and the grayscale images. Once the stenosis
reaches 50% to 90% values, the peak systolic flow is the most accurate parameter. Below
50% stenosis, the spectral broadening is not easily assessed and the grayscale and color
modalities can help to make a diagnosis. Above 90% to 95% stenosis, the peak systolic flow
falls as the stenosis approaches occlusion.
The majority of vascular laboratories in the United States uses the percentage stenosis to
evaluate the need for surgical or endovascular intervention. Other investigators believe that the
residual lumen of the artery is a better predictor of stroke. They suggest that because the distal
lumen of the carotid artery varies from patient to patient (poststenotic dilatation and narrowing)
and is affected by arterial pressure, a comparison among the arterial lumens of various
segments of the artery provides the observer only with a ratio of the narrowed lumen rather
than the true lumen of the artery, which may be more significant. These investigators propose
that a residual lumen of 1.5 mm must be considered hemodynamically significant for the
majority of patients. However, using standard measuring techniques adapted from the North
American Symptomatic Carotid Endarterectomy Trial (NASCET), a narrowed segment
measuring 1.5 mm in diameter, for example, and the distal nonaffected carotid segment
measuring 4.0 mm would be classified as a 62.5% stenosis. The same lesion with a normal
distal carotid artery of 5.0 mm would be classified as an 70% stenosis. Because of these
potential treatment decision-making differences in evaluation of a carotid artery with US, the
Society of Radiologists in Ultrasound developed a consensus opinion for grayscale and Doppler
criteria in which they established the parameters for PSV, percentage stenosis, EDV, and the
ratio between of the PSV of the ICA and the PSV of the CCA (34).
Ultrasonography
Grayscale US is supplemented by spectral Doppler US and color flow vascular imaging. It helps
to identify blood vessels, confirm the presence of blood flow and its direction, detect vessel
stenosis and occlusion, assess perfusion to organs and tissues, and characterize blood flow
dynamics. This technique uses the changes in frequency of the US waves that occur when they
are reflected from the movement of the red blood cells in the circulation. Different analyses can
be made when we process these returning waves reflected by the moving cells; flow velocity,
pattern of blood flow, velocity ratios, and color flow analysis are a few of them.
These methods have many advantages that make them very valuable for evaluating the carotid
arteries; little or no patient discomfort, satisfactory anatomic detail, adequate demonstration of
plaque composition, hemodynamic measurement, and a relatively low cost compared to that of
other methods are a few of them.
There are a few limitations of US, especially when evaluating tandem lesions, lesions close to
the skull base, and lesions near carotid artery occlusions. The major drawback of US is its
inability to clearly demonstrate the cerebrovascular circulation, the collateral circulation, and the
vertebral arteries. Numerous pathologies can easily be missed, such as associated secondary
stenosis within the intracranial circulation, an associated arteriovenous malformation, or
aneurysms. In addition, since US depends on flow velocities, a hyperdynamic state, such as in
sepsis or in patients who are on positive inotropic agents and in conditions that increase the
flow velocity, can lead to an inaccurate assessment of the degree of stenosis. Furthermore, US
may miss an intraluminal thrombus, arterial dissections, and a complete carotid occlusion that
could cause stroke symptoms. US may be difficult in patients with a very short and broad neck.
Finally, US shows a strong interobserver variability, mainly due to degree of experience of
operators. Thus, many physicians combine several other techniques in the preoperative
evaluation of the patient presenting with a stenosis of the carotid artery.
Computed Tomographic Angiography

At most centers computed tomography, unlike MR imaging (MRI), is readily accessible for
imaging of both extracranial and intracranial arteries. Multidetector CTA (MDCTA), with its high-
contrast resolution, allows the differentiation of normal, stenotic, and occlusive disease and the
characterization of atherosclerotic plaques and can provide sufficient information for
appropriate treatment. Images can be displayed with three-dimensional reformatting software
and facilitate evaluation of the carotid stenosis as defined in the NASCET. Similarly to scanner
speed, postprocessing tools have improved dramatically, allowing reconstruction in <20
minutes. However, for proper interpretation of the lesion, axial source images should always be
reviewed carefully. In an acute ischemic setting, imaging of both the cervical and the cerebral
vasculature is vital to differentiate a cardioembolic event from an occlusive disease of the
carotid artery or the intracranial circulation as the cause of ischemia. CTA can be performed in
an emergency setting even in severely ill patients or in patients not suitable for MRI, provided
no contraindication for iodinated contrast material exists.
Modern MDCT scanners permit easy coverage of extra- and intracranial vasculature in a single-
volume data set. Tandem stenoses and intracranial vascular malformations or aneurysm can be
detected, which may be present in 13% to 50% of cases associated with a carotid stenosis
(35, 36, 37). The presence of such additional lesions has a negative predictive value for the
outcome of patients undergoing carotid endarterectomy (CEA) and may also change the
therapeutic approach.
Compared to other modalities, MDCTA images can be obtained fast, there is less discomfort,
and it can be the diagnostic evaluation of choice when the patient has contraindications to
undergoing a MRI. Due to limited spatial resolution, details of the plaques cannot be captured
with MDCTA compared with other modalities such as MRI. This has obvious implications
regarding the stability of the plaque, especially when predicting an impending stroke. Although
less extensively studied, some authors have reported a reasonably good correlation between
CTA and digital subtraction angiography (DSA) in characterization of plaque ulceration (38,39).
CTA has been found to be helpful in cases where Doppler US and MRA showed discordant
results (40). CTA may allow differentiation between dissection and atherosclerotic occlusive
disease by visualizing the intimal flap or atherosclerotic plaque. However, spatial resolution of
DSA still remains superior to CTA. Nevertheless, CTA is highly sensitive in the detection of
carotid artery stenosis and has to be considered as a screening imaging tool for symptomatic
patients (41). Due to artifacts, CTA of the petrous portion of the carotid artery remains a
challenge.
Magnetic Resonance Angiography
MRA allows examination of the intracranial and extracranial vasculature with a high spatial
resolution, noninvasively, and without the need for iodinated contrast agents or ionizing
radiation. In addition to blood flow and flow velocity, information on blood volume can be
obtained if phase-contrast angiography techniques are used (42). The most commonly used
techniques are time-of-flight MRA, phase-contrast MRA, and contrast-enhanced MRA. MRA's
limitations are sensitivity to motion, susceptibility artifacts, pulsatility, signal loss to slow flow,
disturbed flow, and turbulent flow. Similarly to CTA, all the information is contained in source
images, which must be evaluated carefully. If MRA images and/or clinical presentation suggests
an acute dissection, MRI can provide useful additional information on subintimal blood
accumulation by adding thinslice axial T2-weighted images more quickly or fat-saturated T1-
weighted images.
Using time-of-flight techniques, the anatomy of cervical and cerebral vasculature can be
visualized without the addition of intravenous contrast. Increasing the magnet field strength and
adding multiple channels for parallel imaging can help to reduce the acquisition time and
improve the signal-to-noise ratio.
Using phase-contrast techniques, stationary tissue is magnetized in such a way that the phase
is zero, while the phase of flowing blood is not. The images contain information on direction of
blood flow, flow rate, and flow velocity (42). In contrast-enhanced MRA, gadolinium is injected
intravenously as a contrast agent to further shorten the T1 relaxation in flowing blood. This
augments the distinction between moving blood and stationary tissue. Advantages of contrast-
enhanced MRA over nonenhanced MRA are improved image quality due to decreased
susceptibility artifacts, shorter acquisition times (43), and lower sensitivity to disturbed flow,
which may falsely overestimate a carotid stenosis. Anatomic details on MRA are poorer
compared with DSA, especially when information on collateral blood circulation is of
importance.
Digital Subtraction Angiography

Angiography has been and remains the gold standard for the evaluation of patients with
cerebrovascular disease with the highest sensitivity (Fig. 9-1). The angiogram defines the lesion
and its architecture, outlines potential collaterals and dangerous anastomoses, and helps with
planning of endovascular therapy and device selection. The femoral artery approach is the most
common site of arterial access for cerebral diagnostic angiography and intervention, but other
alternatives are radial, brachial, and direct carotid approaches. One of the most important
advantages of angiography is the ability to evaluate the entire cerebrovascular arterial and
venous system. DSA can provide anatomic detail, with high spatial and temporal resolution of
the aortic arch, the brachiocephalic trunk, the common carotid arteries, the vertebral arteries,
and the intracranial circulation. DSA has a detection rate of only 60% to 73% for ulceration,
when correlated with results from surgery (44,45). More recent data from flat-panel technique
do suggest that these numbers may be improved (46, 47, 48, 49). Flat-panel detectors provide
high-resolution angiograms and soft tissue images of the surrounding structures and the brain
(cone beam reconstruction). In the near-future brain evaluation of perfusion changes during or
after intervention necessitating adjustment of the blood pressure will help to reduce the
periprocedural morbidity and mortality associated with stenting. Improvement of angiography
equipment, improvement of catheter technology, and introduction of iso-osmolar nonionic
contrast materials have all added to minimize the complications of diagnostic neuroangiography,
which in experienced hands should be <0.05%.
Evaluation of Carotid Artery Occlusion

The delineation between an occlusion and a severe carotid artery stenosis, also know as string
sign, is important because of varying treatment options. CEA or stenting may be offered to a
patient with a severe carotid stenosis, while a patient with
a carotid occlusion may benefit from extracranial/intracranial bypass surgery. Noninvasive
modalities such as US Doppler, color Doppler, CTA, and MRA are not always able to make this
distinction. Thus, DSA is required infrequently to establish the diagnosis and provide detailed
information on the collateral circulation.
FIGURE 9-1. A: Contrast-enhanced MRA gradient recalled three-dimensional time-of-flight
sequence with maximum-intensity projection reconstructions show a long segment of
tapered narrowing of the proximal portion of the right ICA (arrow). The distal cervical
segment is diffusely narrowed and the assessment of its lumen is limited. B: DSA of the
ICA in lateral view shows a dissection with significant narrowing up to the horizontal
segment of the petrous portion. Note the poor antegrade blood flow.
TREATMENT
Medical Management and Carotid Endarterectomy
Preventive measures, especially in the high-risk population, may be effective in reducing the
morbidity and mortality of stroke. Stroke awareness programs as well as antiplatelet and
anticoagulation treatment are preventive medical measures that are vital. Surgical management
is the treatment of choice in symptomatic highly stenotic lesions. Endovascular recanalization
including carotid, vertebral, and intracranial stenting is an effective and safe treatment modality
for prevention and treatment of ischemic stroke associated with atherosclerotic occlusive
disease.
Surgery of carotid artery disease is performed to prevent embolic stroke and, on rare
occasions, to improve hemodynamic-related neurological symptoms due to a high-grade
stenosis, for example, radiation-induced stenosis or high-grade lesion of a carotid artery, which
may serve as a collateral blood supply to the posterior circulation in the case of a basilar and
vertebral artery occlusion. CEA is an operation that involves removal of the carotid plaque
including the inner lining of the artery that has become thickened or damaged. CEA restores the
blood flow and reduces the risk of arterio-arterial emboli. C. Miller Fisher's report (14) on the
relationship between carotid artery disease and stroke served as a basis for Eastcott et al.,
who described the first surgical carotid reconstruction in 1952 and the first successful carotid
endarterectomy in which the circulation to the brain was intentionally interrupted to remove a
stenotic plaque in 1954 (50,51). In 1953, DeBakey (52) performed the first CEA in the United
States for the treatment of an occluded cervical carotid artery. Carotid surgery remained
controversial for decades. Only recently did the European Carotid Surgery Trialists' (ECST)
Collaborative Group (53, 54, 55) and the NASCET address the benefit of treating carotid artery
stenosis to decrease the risk of stroke (56).
The NASCET was a randomized study that found that CEA reduces the risk of stroke in
symptomatic patients with ipsilateral high-grade carotid artery stenosis (70%-90%) (57). The
study showed a statistically significant reduction in ipsilateral stroke over a period of 24 months
in the CEA arm, to 9%, compared with patients who received medical treatment only (n = 331;
26% ipsilateral stroke). Patients in both groups received antiplatelet therapy (ASA = aspirin;
1300 mg daily PO) and antihypertensive, antilipid, and antidiabetic medications. The overall
perioperative stroke and death rate for the 328 patients treated in the NASCET was 5.8%.
Even though there were other associated complications such as cranial nerve injury (7.6%),
myocardial infarction (0.9%), arrhythmia (1.2%), congestive heart failure (0.6%), wound
infection (3.4%), wound hematoma (5.5%), and other cardiovascular problems (1.2%), CEA
became the standard of care for symptomatic high-grade (>50%) carotid artery stenosis. The
NASCET also demonstrated a correlation between the degree of stenosis and the risk of
stroke. For patients with 70% to 79% stenosis, the risk of stroke was 12%. For those who had
80% to 89% stenosis the risk was 18%, and for those in which stenosis was >90% the risk
was 26%. The study was terminated early because of the strong evidence of surgical efficacy
in the patients with severe stenosis (56).
The annual stroke event rate for asymptomatic patients with hemodynamically significant
carotid artery stenosis ranges from 2% to 5% (57). The 5-year stroke and death risk for an
asymptomatic high-grade carotid stenosis with medical treatment was found to be 11%, while
the surgical arm had a stroke risk of 5.1%. The Asymptomatic Carotid Artery Stenosis Study
(ACAS) trial justified CEA in asymptomatic males with 60% stenosis only if the perioperative
morbidity and mortality rate of the procedure is <3.0% (57). The acceptable perioperative
morbidity/mortality rate for symptomatic patients is 6%. Although the findings were not as clear
for females, women also experienced a reduction in stroke risk with CEA.
Carotid Artery Angioplasty and Stenting

Patients who are not good candidates for CEA and continue to have TIA on optimal medical
therapy should be considered for carotid angioplasty and stenting. Also, patients who fall into
the following categories should also be considered for carotid artery angioplasty/stenting:
patients with lesions that are anatomically inaccessible to surgery, patients with lesions with
CEA restenosis, high-risk patients with severe comorbidities, patients with lesions from
radiation-induced stenosis, medically refractory patients, cases with associated dissections,
and patients with tumor-encased carotid arteries. In the NASCET, there was a subgroup of
patients who were classified into a high-risk population that could benefit for carotid stenting
(CS) (56). These patients were excluded from the study if they were mentally incompetent or
unwilling to give informed consent, had inadequate angiographic visualization of both carotid
arteries and their intracranial branches, and/or had an intracranial lesion that was more severe
than the surgically accessible lesion (Fig. 9-2). Those with symptoms that could be attributed to
nonatherosclerotic disease or progressing neurological signs had previously undergone an
ipsilateral carotid endarterectomy and patients >79 years of age were not included either
(Table 9-1).
FIGURE 9-2. A 75-year-old male with a stroke associated with a bilateral ICA stenosis
(ICA), right middle cerebral artery (MCA) stenosis (tandem lesion) with mild poststenotic
dilatation, and multiple areas of atherosclerotic narrowing of both vertebral artery origins
and both intracranial vertebral arteries at the vertebrobasilar junction. (A) Right ICA origin
stenosis in frontal view (arrow) and (B) ipsilateral MCA stenosis (curved arrow). (C)
Angiogram in frontal view after stenting and (D) poststent PTA. (E) Final angiogram in
lateral view and (F) 3-month follow-up. (G) PTA of MCA stenosis and (H) placement of a
Wingspan (Boston Scientific, Natick, MA) self-expanding intracranial Nitinol stent (arrows).
(I) Final angiogram after stent deployment and (J) 3-month follow-up with mild residual
narrowing of the M1 segment (curved arrow). (K) Three-month follow-up angiogram shows
both the stented ICA (arrow) and the MCA lesion (curved arrow); note the stented
contralateral ICA (double arrow).
FIGURE 9-2. (Continued)
High-risk surgical patients, such as patients with organ failure of the kidney, liver, or lung,
cardiac valvular or cardiac rhythm disorder likely to be associated with cardioembolic
symptoms, patients who had experienced angina or myocardial infarction in the previous 6
months, patients who had cancer judged likely to cause death within 5 years, and patients who
had a cerebral infarction on either side that deprived him or her of all useful function in the
affected territory should be considered for carotid artery stenting. Most of the initial CS trials
have recruited patients who were considered high-surgical-risk candidates and presented with
a restenosis after previous CEA, had a lesion in a surgically inaccessible areas (Fig. 9-3),
presented with an arterial dissection (Fig. 9-4), had radiation-induced stenosis (Fig. 9-5), had
symptoms related to a tumorencased artery, or were >80 years of age (58, 59, 60) (Tables 9-
2, 9-3 and 9-4). Since the onset of CS, multiple trials have demonstrated reduced
periprocedural morbidity and mortality of endovascular treatment compared with surgery,
especially if distal cerebral protection (CP) is used during CS.
TABLE 9-1 PATIENTS EXCLUDED FROM THE NORTH AMERICAN
SYMPTOMATIC CAROTID ENDARTERECTOMY TRIAL
Mentally incompetent or unwilling to give informed consent
Inadequate angiographic visualization of both carotid arteries and their intracranial

branches
Intracranial lesion more severe than the surgically accessible lesion
Organ failure of the kidney, liver, or lung, or cancer judged likely to cause death within
5 years
Cerebral infarction on either side that deprived the patient of all useful function in the
affected territory
Symptoms that could be attributed to nonatherosclerotic disease
Cardiac valvular or rhythm disorder likely to be associated with cardioembolic

symptoms
Having previously undergone an ipsilateral carotid endarterectomy
Age >79 years
Having experienced angina or myocardial infarction in the previous 6 months
Progressing neurological signs
Contralateral carotid endarterectomy within 4 months
Having undergone a major surgical procedure within 30 days
Source: Reprinted with permission from North American
Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid

endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J
Med. 1991;325:445-453.
The Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) was a
randomized trial that compared endovascular treatment with CEA (61). This multicenter trial
conducted in Europe, Australia, and Canada randomly selected 504 patients with carotid
stenosis. Patients with stenosis of the CCA, carotid bifurcation, or ICA that needed treatment
were included only if both endovascular and surgical treatments were suitable. The CEA group
included 253 patients and the endovascular group included 251 patients. Stenting was used in
55 patients (26%) and angioplasty alone was used in 158 patients (74%). The mean stenosis in
the surgical arm was 86.4% and the 30-day stroke and death rate was 5.9%. In the
endovascular group, the mean stenosis was 85.1% and the 30-day stroke or death risk was
6.4%. There was statistically no significant difference between the two groups.
The Carotid Revascularization Endarterectomy Versus Stent Trial (CREST) is currently enrolling
patients for a multicenter clinical trial to compare the efficacy of CEA and CS in symptomatic
patients with significant stenosis (62). This study is evaluating whether CS is more or less
efficacious than CEA. The latest update on the global carotid stent registry includes almost
11,243 stented patients with more than 12,392 carotid arteries stented (63). Data show that
the technical success with stenting was >98.9%. The minor and major stroke risk and mortality
without the use of a distal CP device was 3.98%, whereas the use of a distal CP device
reduced the risk of stroke to 2.23%. In >10 industry-sponsored registries, the 30-day rates of
adverse effects including stroke, death, and myocardial infarction were 2% to 9%. More than
25,000 patients have undergone stenting procedures; the technical success rate is 96%.
Results have varied over time, depending on various factors: population studied, devices used,
timing of follow-up evaluations, technology, sample, and the use of distal protection. There are
also randomized trials comparing CEA and stenting in nonrisk patients.
More than 13 trials have been launched since 1997. Carotid Revascularization Using
Endarterectomy or Stenting Systems (CaRESS) investigated whether CS with CP is
comparable to CEA in patients with symptomatic and asymptomatic carotid stenosis (64). A
total of 397 patients (254 CEA and 143 CS) were enrolled in the study; 32% of the patients
were symptomatic and 68% were asymptomatic. The study showed that there were no
significant differences in combined death/stroke rates at 30 days (3.6% CEA versus 2.1% CS)
or at 1 year (13.6% CEA versus 10.0% CS). There were no significant differences in the
combined end point of death, stroke, or myocardial infarction at 30 days or at 1 year (64).
Residual stenosis, restenosis, and change in quality of life were compared between the two
modalities and no significant differences were found. The most recent results of the large
Stenting and Angioplasty with Protection in Patients at High Risk of Endarterectomy
(SAPPHIRE) trial in high-risk patients undergoing CS with the use of distal protection
demonstrated that CS is not inferior to CEA (65). The primary end point of the study was the
cumulative incidence of a major cardiovascular event at 1 year, a composite of death, stroke, or
myocardial infarction within 30 days after the intervention, or death or ipsilateral stroke at
between 31 days and 1 year. The study was designed to test that CS was not inferior to CEA.
The primary end point occurred in 20 patients randomly assigned to undergo carotid artery
stenting with a cerebral embolus-protection device (cumulative incidence, 12.2%) and in 32
patients randomly assigned to undergo endarterectomy (cumulative incidence, 20.1%; absolute
difference, 7.9 percentage points; 95% confidence interval, 16.4 to 0.7 percentage points; p =
0.004 for noninferiority, and p = 0.053 for superiority). These numbers are higher than those
presented by other trials, but the study was focused on high-risk patients only. In the
periprocedural period, the cumulative incidence of death, myocardial infarction, or stroke among
patients with asymptomatic carotid artery stenosis was 5.4% among those who received a
stent, compared with 10.2% among those who underwent CEA (p = 0.20).
The Carotid Stenting Trial for High-Risk Surgical Patients (BEACH) is a multicenter prospective
registry designed to evaluate the outcomes of patients with carotid artery stenosis, at high risk
for CEA, using stenting and distal protection devices. A total of 747 patients have been enrolled
with both symptomatic and asymptomatic carotid lesions. The technical success rate for stent
in conjunction with the CP distal filter device has been 98.2% and the overall procedure success
rate after stent deployment is 98%. The 30 day composite major adverse event rate is 5.8%
including death, stroke and myocardial infarction (66). The ACCULINK for Revascularization of
Carotid in High Risk Patients) trial (ARCHeR 1) was performed without a CP device and the 30-
day stroke rate was 4.4%, with a death rate of 2.5%. A total of 339 patients were originally
enrolled, but 158 of them were then enrolled in ARCHeR 2, in which a CP device was used
(67).
A variety of neuroprotective devices is likely to be optimized to decrease the incidence of
embolic debris events. Drug-coated and low-profile covered stents will also play a role in
carotid stent development. Other ongoing trials will evaluate also whether carotid artery
stenting is beneficial in other subgroups, such as low-risk and asymptomatic patients.
FIGURE 9-3. Symptomatic high-grade right ICA stenosis (arrows) in a 70-year-old male.
A: The lesion is surgically difficult to access and located proximal to the tortuous turn of the
ICA into the petrous canal. Mild ICA origin narrowing (<10%) requiring no treatment
(curved arrow). B: Precise placement of a self-expanding stent over an 0.018-in. soft-tip
wire (arrow). Note the residual central narrowing. C: Poststent PTA with complete ICA
revascularization.
Cerebral Protection Devices

Carotid plaques can be extremely friable and lead to arterio-arterial emboli during carotid
angioplasty and stenting; any type of manipulation may potentially cause plaque fragmentation,
distal embolization, or occlusion (68). Fragmented particle sizes range from 20 to 400 m but
can be larger, up to 1,000 m.
Although many distal protection devices have been developed to alleviate embolic
complications, three main categories of devices exist. The most common type is the filter
device that is navigated distal to the stenosis and expanded to catch embolic particles (Fig. 9-
6). This device allows distal arterial perfusion through the holes of the filter, which is collapsed
at the end of the procedure and retrieves the particulate matter after removal from the artery.
However, it has been argued that the filter device allows the passage of tiny particulates, <80
to 100 m. Emboli <100 m are thought to account for the majority of embolic debris, yet the
clinical significance of such small emboli is not fully understood. The umbrella design of the filter
is intuitively sensible and may be less traumatic to the vessel wall due to less external forces.
Devices that are currently being used or tested include the following: Accunet (Guidant Corp.,
Indianapolis, IN), FilterWire EX (Boston Scientific, Natick, MA), AngioGuard (Cordis Corp.,
Minneapolis, MN), and MedNova NeuroShield (MedNova Inc., Galway, Ireland).
The second type of device is the balloon occlusion device that is expanded and completely
prevents antegrade flow. The balloon is expanded as long as it takes to treat the vessel
including angioplasty and stenting. Prior to deflation, the material is aspirated from the vessel
through a special aspiration catheter. The most popular device on the market is the PercuSurge
GuardWire PlusTM Temporary Occlusion and Aspiration System (PercuSurge, Inc., Sunnyvale,
CA, a division of Medtronic, Inc., Minneapolis, MN), and The Guardian System (Rubicon
Medical, Salt Lake City, UT). The advantages include its ability to more completely capture both
large and small particles; the design is technically easier to use, with less potential mechanical
problems because of the simple balloon inflation and deflation, and it provides temporary and
complete vessel occlusion during maximal times of embolization. However, temporary occlusion
of the carotid may not be tolerated in all individuals, especially patients with significant bilateral
carotid stenosis. It has been shown that less than 10% of individuals treated may not tolerate
complete cessation of blood flow for greater than 5-15 minutes. Also, particles may be
redirected into the external carotid artery during aspiration or pressure injection and be washout
through dangerous anastomoses into the anterior or the posterior circulation. The balloon may
not completely deflate or could possibly get caught on the stent and subsequently tear.
FIGURE 9-4. A: Dissection of the left ICA with poor distal flow (curved arrow) in a 42-
year-old female with a severe acute stroke with a poor response to intravenous tPA. B:
Right ICA angiogram shows no collateral blood supply through the A1 segment of the
anterior communicating artery. C: Right vertebral artery angiogram in frontal view clarifies
the intracranial blood circulation. Obliteration of left MCA posterior division and A1/A2
junction due to an embolus most probably originating from the dissection. D: Lateral ICA
angiogram after acute stenting that was performed within 2 hours after the stroke onset
(arrow). E: Left intracranial circulation after intra-arterial local thrombolysis with
recanalization of anterior cerebral artery (A1/A2 junction; arrow). F: After thrombectomy of
the embolus in the left MCA, with complete distal blood flow restoration (curved arrow). At
30-day office visit the patient had no neurological deficit.
FIGURE 9-5. Intractable pharyngeal bleed in a 65-year-old male with (A) a radiation-
induced carotid stenosis (arrow) and a pseudoaneurysm of the lingual artery (curved
arrow); the lingual artery is obliterated. (B) Coiling (double arrow) and obliteration of the
aneurysm and (C) revascularization of the ICA with two overlapping self-expanding stents
(arrows). D: Final angiogram shows a mild distal vasospasm (arrow).
TABLE 9-2 ANATOMICAL HIGH-RISK POPULATION
Surgically inaccessible lesion above C2 or below the clavicle
Previous head or neck radiation therapy
Surgery that included the area of stenosis/repair
Ipsilateral neck dissection for cancer surgery
Spinal immobility of the neck due to cervical disorders
Restenosis after previous or unsuccessful attempt
Presence of laryngeal palsy
Presence of tracheotomy
Contralateral total occlusion of the carotid artery
Tandem lesions
The third type is a catheter occlusion device; the Parodi Anti-Emboli System (PAES; ArteriA
Medical Science, Inc., San Francisco, CA) best exemplifies this type (69). It is a guiding
catheter with an occlusion balloon at its distal end. It works by reversing the blood flow in the
target artery. It is placed in the CCA and the balloon occlusion creates a negative pressure
gradient distal to the balloon that causes retrograde flow into the ICA. The external carotid
artery is also occluded to prevent flow and emboli from traveling in that vessel. The advantages
include the ability to obtain complete protection prior to manipulation of the lesion. It is also able
to capture particles of all sizes, and it facilitates treatment of tortuous and tight lesions since it
does not have to be passed through the arterial lesion. It does, however, require a larger
puncture site in the groin and interrupts flow during the protection time and may not be tolerated
by all patients (70). The use is also cumbersome and time-consuming.
Restenosis After Carotid Artery Stenting

Restenosis is not uncommon after CEA. Studies have reported incidences anywhere from 1.5%
in symptomatic to 19% in asymptomatic patients. Furthermore, reoperation is frequently more
difficult for restenosis after CEA, with higher rates of local and neurological complications (14).
Unlike in the peripheral and coronary system, restenosis or in-stent stenosis after CS has rarely
been described. In more than 12,000 cases of carotid artery stenosis treated, the rate of
restenosis at 48 months was 2.6% (63). Other studies with follow-ups of 1 year have reported
in-stent stenosis rates after carotid angioplasty and stenting of between 3.5% and 8.0% (71).
Stenting of vessels has been shown to overcome previously high rates of restenosis with
angioplasty alone.
TABLE 9-3 MEDICAL HIGH-RISK POPULATION
Congestive heart failure (New York Heart Association III/IV)
Unstable angina (Stage III/IV)
Pre Coronary Artery Bypass Graft or valve replacement procedure
Chronic obstructive pulmonary disease (Forced expiratory volume <30%)
Left ventricular ejection fraction <30%
Age >75 years
Recent myocardial infarction
Two or more diseased coronary arteries >70%
TABLE 9-4 INCLUSION AND EXCLUSION CRITERIA FOR CAROTID

ARTERY STENTING
Inclusion criteria
Symptomatic carotid artery stenosis >50%
Asymptomatic carotid artery stenosis >80%
Exclusion criteria
Bleeding disorders that preclude antiplatelet medication
Allergy to antiplatelet medication
Chronic carotid artery occlusion
Positive blood cultures/sepsis
Immunocompromised state
Recent history of intracranial hemorrhage
Acute large middle cerebral artery stroke (<4- to 6-week-old infarct)
Fresh clot within stenosis (relative contraindication)
Recent history of intracranial hemorrhage
Carotid Artery Stenting in Octogenarians

The incidence of stroke increases dramatically with age, becoming the second most common
cause of death by the age of 85 years (72). In addition, because of aging of the general
population, the number of patients with symptomatic extracranial ICA stenosis is increasing
(73). Because advanced age (i.e., >80 years) is a risk factor for morbidity after surgery, these
patients were excluded from the NASCET (56). Direct comparison of carotid angioplasty and
CS versus CEA showed that CS can be performed with low perioperative stroke and death
rates, in particular, in patients with high risk factors for CEA (74, 75, 76, 77).
A few reports have suggested that in addition to CEA, CS may also be associated with
increased periprocedural complications in the older age group. In the largest single-center
series to date of CS in patients >80 years old, advanced age was a significant predictor of
periprocedural stroke and death rate in patients who underwent stenting. In addition, results
from the lead-in phase of the multicenter CREST showed that the periprocedural risk of stroke
and death after CS increases up to 12.1% in octogenarians (78). A total of 749 patients
undergoing CS, 30.7% symptomatic and 69.3% asymptomatic, were included in this study.
Patients were subdivided into four age categories: <60, 60 to 69, 70 to 79, and 80 years.
Stroke and death during the 30-day periprocedural period were calculated for each group. An
increasing proportion of patients suffered stroke and death with increasing age: 2 (1.7%) of
120 patients <60 years of age, 3 (1.3%) of 229 between 60 and 69 years of age, 16 (5.3%) of
301 patients between 70 and 79 years of age, and 12 (12.1%) of 99 patients >80 years of
age. The study attributed half of the complications in this sub-group to bradycardia and arterial
hypotension after balloon dilatation. These results prompted the committee to no longer include
octogenarians in the lead-in phase of the trial.
With regard to CS with an embolus protection device, Chastain et al. showed that the 30-day
stroke and death rate in octogenarians who underwent CS was 16%, compared to 8.2% for
younger patients (79). The complication rate in octogenarians was reduced to 8.5% when CP
was used (80). On the other hand, Shawl et al. reported a 2.9% 30-day stroke rate, with no
deaths observed in 42 octogenarians who underwent CS without CP (81).
Considering data from controlled trials that included patients at high risk for CEA, such as
SAPPHIRE (Stenting and Angioplasty with Protection for Patients at High Risk for
Endarterectomy) (65) and CARESS (64), the 30-day major stroke
and death rates were, respectively, 4.8% and 2.1%. These trials did not report an increase in
major complication rates among patients >80 years of age.
FIGURE 9-6. A: Oblique view of a right common carotid angiogram in a 71-year-old female
with TIA shows a high-grade (>95%) stenosis of the right ICA (arrow). A poststenotic
collapse of the ICA is noted, with a tandem stenosis involving (B) the petrous portion
(curved arrow) and the supraclinoid segment of the ICA (arrow). C: Placement of a PTA
balloon leads to a complete occlusion of the ICA (arrow). D: Inflation of the PTA balloon to
6 atm (arrow). E: Post-PTA angiograms show the marker of the cerebral protection device
(curved arrow). F: Placement of a self-expanding stent; note the incomplete expansion in
the central part of the stent covering the plaque (arrow). G: Poststent angioplasty with
complete revascularization of the ICA. Note the remaining petrous stenosis (arrow).
However, the treatment of ICA stenosis in patients >80 years remains controversial. In a series
of 9,918 patients who underwent CEA in Maryland from January 1990 through December 1995,
octogenarians did not experience a higher periprocedural complication rate (82). The authors
reported a 30-day stroke and death rate of 1.3% in patients >80 years, which was not
significantly different from the overall rate of 1.2% for younger patients. But other authors have
reported a fourfold increase in mortality in patients >80 years after CEA (83). Additional reports
on CEA showed a complication rate of 11.8% for ages >75 years and 5.9% for ages <75 years
(84). Multicenter randomized studies are needed to address the periprocedural morbidity and
mortality of octogenarians.
Procedural Protocol
Some general rules for carotid artery stenting exist to minimize the periprocedural risks.
However, most operators will adjust details based on their needs and experience. Prior to the
procedure, all patients should undergo a thorough baseline physical assessment, a
comprehensive neurological examination, MRA/MRI, CT/CTA, ECG, and US. Blood work should
include routine electrolytes, complete blood count, chemistry panel, blood urea nitrogen,
creatinine, prothrombin, prothrombin time, INR, Hematocrit/Hemoglobin (H/H), complete blood
cell count, red blood cell count, and platelet count. Also, female patients of child-baring age
should undergo a urine pregnancy test prior to exposure to radiation.
Patients should be NPO for at least 6 hours prior to stenting. -Blockers should be ceased prior
to the procedure because of the risk of exacerbating bradycardia associated with stenting
carotid bulb lesions. Other medications such as insulin and coumadin should be closely
monitored. Special attention should be paid to possible latex or contrast allergies.
Protocols may differ slightly based on the timing of the procedure, specifically if the procedure
is elective or emergent. For elective procedures, patients are premedicated with Plavix
(clopidogrel), 75 mg, and aspirin, 325 mg PO qd 2-4 days. In an acute procedure, a loading
dose of Plavix, 375mg, and aspirin, 650 mg PO, is given 3 to 4 hours prior to the procedure.
Patients who cannot tolerate Plavix are provided with ticlopidine, 250 mg bid (total dose
preprocedure, 500 mg) as an alternative. Fentanyl, 50 to 150 g IV, and Versed, 1 to 2 mg, are
used to initiate conscious sedation. Dependent on mental status, some patients may require
general anesthesia.
Usually CS is performed in patients heparinized to maintain an activated clotting time (ACT) of
250 to 300 seconds. Generally postprocedural heparinization is not required. Glycoprotein
IIb/IIIa receptor blockers may rarely be required in carotid artery stenting. The ACT is
maintained near 200 seconds if GP IIb/IIIa receptor blockers are used, to avoid increased risk
of brain hemorrhage after revascularization. Options include Integrelin (eptifibatide), 180 g/kg
initial bolus, with a second 180 g/kg bolus 10 minutes later. Another choice is the glycoprotein
IIb/IIIa receptor antibody blocker, abciximab (ReoPro, 0.25 mg/kg bolus). If glycoprotein IIb/IIIa
receptor blockers are not used, the ACT is maintained at between 250 and 300 seconds. A
20% albumin IV infusion (over 20 min, every 4-6 hours) can be given as a volume expander if
the patient experiences significant periprocedural hypotension.
Primary stenting should be the goal to reduce periprocedural morbidity. This can be achieved in
most cases, especially when using low-profile stents with minimal longitudinal
shortening during deployment. Braided stents with significant shortening will more frequently
require percutaneous transluminal angioplasty (PTA) or will otherwise tend to jump proximally or
distally to the stenosis (watermelon seed effect).
Patient preparation includes the placement of an IV line with 0.9% normal saline infusion at 150
to 200 mL/hour. The access point for the procedure is the femoral artery. Infrequently, the
brachial, radial, or carotid artery might be directly accessed. A 5-Fr femoral sheath is then
placed. An IV heparin bolus of 2,000 to 7,000 IU is provided, and the ACT is adjusted to 200
seconds if glycoprotein IIb/IIIa receptor blockers are used. Angiography of both the iliac and
the femoral arteries is performed because many patients with carotid stenosis will also have
stenoses of the peripheral circulation, which might also require revascularization.
A 5-Fr diagnostic catheter (Berenstein II, Multipurpose, Sidewinder II; Cordis J&J, Miami
Lakes, FL) is used to perform four-vessel angiography of both the anterior and the posterior
circulation to evaluate the degree of stenosis (NASCET criteria) and other vascular
abnormalities, such as tandem lesions and intracranial aneurysms. The diagnostic catheter is
then parked in the CCA for acquisition of a roadmap. With the help of a 0.35-in. glide wire, the
catheter is placed in the external carotid. The glide wire is then exchanged for a 0.038-in.,
extrastiff, 260-cm wire (0.38-in. Amplatz wire, 260 cm; Cook, Inc., Bloomington, IN). The
diagnostic catheter is then removed, and a guide catheter is inserted (6 Fr or, infrequently, a 7-
Fr Shuttle; Cook, Inc.) within the CCA, proximal to the target site. Angiograms are obtained to
measure the arterial dimensions and the length of the lesion. At this point, a decision should be
made for either primary stenting or preprocedural PTA.
For primary stenting, a 300-cm, 0.018-in., exchange wire (e.g., SV 5/8; Cordis J&J) should be
inserted into the stent delivery system. Either bony landmarks (vertebral body on lateral
projection) or the roadmapping technique can be used for navigational reference. Plaque
classification may help in localizing the area of stenosis for final stent placement. The wire is
then navigated through the lesion, and the stiff part of the wire is placed across the stenosis.
After stabilizing the wire, the stent is placed within the stenosis. The slack of the delivery
system is taken out prior to deployment. The stent is then deployed, and the delivery system is
subsequently removed. In tight lesions, the delivery system may need to be resheathed distal to
the stented artery prior to removal to prevent the delivery system from being caught by the
struts of the stent. A control angiogram is then obtained to visualize the stented segment and
the intracranial circulation. Depending on the remaining degree of stenosis, the stent is dilated
with a PTA balloon. Investigators recommend slow inflation over several minutes; pressures of
4 to 8 atm are generally adequate to open up the stent.
In secondary stenting, the 0.018-in. exchange wire is navigated through the lesion with a PTA
balloon (e.g., Savvy, 3.0-3.5 20 mm; Cordis J&J). The balloon is then placed within the
stenosis and inflated very slowly (up to several minutes) at pressures ranging from 4 to 8 atm.
Control angiography should be performed after the PTA and should include the intracranial
circulation. Stenting should proceed as discussed above. Patients are put on Plavix, 75 mg PO
qd, and aspirin, 325 mg PO qd, for 6 weeks poststenting. After 6 weeks, patients are
instructed to take only aspirin, 81 mg PO qd, for life.
In case a rapid exchange or monorail CP device is combined with stenting, depending on the
system used, the device is placed in a straight segment of the ICA. The diameter of the device
should not significantly exceed the diameter of the ICA to avoid vessel injury. The CP wire,
generally 0.014 in., serves to navigate not only the stent delivery system, but also the PTA
balloon needed for angioplasty prior to and after stenting. Infrequently vasospasm may be
encountered, which generally does not need any special treatment. On rare occasions, intra-
arterial nicardipine, 5 to 10 mg, given through the guide catheter may be needed to treat severe
vasospasm.
After the completion of stenting, the introducer catheter (Shuttle) is removed and the femoral
access is percutaneously sutured (e.g., Perclose, Abbott Laboratories, Redwood City, CA:
Angioseal, Sherwood Medical Co., St. Louis, MO; Vasoseal, Datascope Corp., Mahwah, NJ).
Common complications include bradycardia and hypotension, which can be prevented by
applying slow inflation and lower pressures during PTA. Atropine, 0.6 to 1.0 mg IV,
glycopyrrolate, 0.4 mg IV, and dopamine are very rarely necessary to treat these
complications, but are options should the need arise. Vasospasm during catheterization, PTA,
or stenting generally does not require any treatment because of its spontaneous resolution,
although, infrequently, papaverine, mannitol, or nicardipine may be used. Dissections producing
intimal flaps during catheter manipulation, PTA, or stenting may require further extensive
stenting to avoid carotid artery occlusion.
Patients are kept for 24 hours in a critical care/step-down unit prior to discharge. Special
attention should be paid to hypo-/hypertension and new neurological symptoms (NIH stroke
scale), including headaches, which can be related to hyperperfusion syndrome or cerebral
hemorrhage. Patients can be ambulated the next day and resume normal activities within a few
days. A carotid US of the stented artery can be obtained prior to discharge to rule out any clots
on the stent, which can develop into larger clots. Clinical follow-up is suggested at 1 month, 3
months, 6 months, and 1 year. Patients should monitor themselves for groin hematoma, fever,
and neurological symptoms (e.g., amaurosis fugax, headaches, aphasia, and sensory or [fine]
motor impairment). Doppler US to monitor restenosis is recommended at 3 months, 6 months,
and 1 year.
SUMMARY
Stroke is the third leading cause of morbidity and mortality in the United States. In one fifth of
patients, carotid artery stenosis is the cause for an arterio-arterial embolic stroke. Diagnostic
cerebral angiography still remains the best way to evaluate the anatomy and pathology of the
vessels in the neck and head including the collateral blood supply. However, CTA and contrast
MRA are gradually replacing diagnostic catheter angiography. CEA has been the procedure of
choice for many years, with successful results, and low periprocedural morbidity, to prevent
stroke. Recently, CS has gained acceptance and various trials have shown that there is no
difference in complications between CS and CEA. CS is a less invasive procedure and can be
safely executed in a select group of patients. The addition of CP devices seems to be
decreasing the stroke rates associated with embolic debris detached from plaque during
stenting. Results of currently ongoing trials could place stenting as a preferred procedure to
treat carotid stenosis in the near-future. More research is necessary to evaluate the treatment
of asymptomatic patients with <80% stenosis. Carotid disease in patients >80 years of age
leads to severe disability and death. Treatment options remain controversial and should be
carefully considered. The choice between CEA and CS should be made in light of
advancements in stent technology, operator experience, and safer devices. In the future,
carotid artery stenting will most likely become safer, with fewer complications, as technological
advances and materials advances accommodate current limitations. These include dedicated
CS equipment with low-profile stent delivery systems and a variety of covered and drug-coated
stents.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 10 - Endovascular Repair of
Descending Thoracic Aortic Aneurysms and Blunt Traumatic Aortic Injury
Chapter 10
Endovascular Repair of Descending Thoracic Aortic
Aneurysms and Blunt Traumatic Aortic Injury
Todd E. Markowitz
Michael D. Dake
Diseases of the thoracic aorta have traditionally been treated with a combination of medical
therapy and open surgical repair based on the specific disease process being addressed, the
size of the aorta, the symptomatology of the patient, and the concurrent medical comorbidities
in this inherently older patient population. Specifically discussing thoracic aortic aneurysms
(TAAs) traditional surgical management has been reserved for patients with aneurysms larger
then 5-6 mm, rapidly expanding aneurysms, symptomatic aneurysms, and patients who present
with rupture (1,2).
The first operative repair of a descending TAA was described by DeBakey and Cooley in 1953
(3). Traditional operative repair requires thoracotomy, possible aortopulmonary bypass, aortic
cross clamping, and interposition graft placement (1). Yet, even with the advancements made in
management of medical comorbidities, early TAA diagnosis, operative technique, anesthesia,
and postoperative care and newer adjunct procedures to prevent complications, there remains
a substantial operative morbidity and mortality (1,2,4, 5, 6) related to surgical repair. Thus, the
exploration for more minimally invasive treatment options for diseases of the thoracic aorta
have been met with the promising evolution of endovascular stent-graft technology.
Transluminally placed endovascular stents was first conceptualized by Dotter in 1969 (7). Since
that time stent technology has grown significantly and has become part of the armamentarium
in the treatment of peripheral vascular disease in numerous vascular beds. Based on this, stent-
graft technology for the treatment of diseases of the aorta evolved. Its first clinical use was
described by Parodi, Palmaz, and Barone (8) for the treatment of abdominal aortic aneurysms
(AAAs) in 1991. Indeed, the majority of the clinical data on endovascular aortic repair come
from the treatment of AAAs. The excitement over the initial and midterm results of AAA
endovascular repair has led investigators to search for new and innovative ways to apply this
technology in the thoracic aorta and in other areas of the arterial tree.
Adaptation of stent-graft technology for use in the thoracic aorta was first described by Dake et
al. in 1994 (9). The early use of first-generation homemade devices has paved the way for
the development of more streamlined commercially available devices, with the first commercial
device gaining U.S. Food and Drug Administration (FDA) approval for the treatment of TAA in
March 2005. In addition, over the past decade stentgraft technology has evolved to treat a
number of thoracic aortic diseases including aortic dissection, traumatic aortic injury, and aortic
rupture.
This chapter reviews the use of stent-graft technology in the treatment of TAAs and traumatic
aortic injury. It begins with a brief description of the current available devices. This is followed
by a discussion of various technical aspects of thoracic endovascular repair including the
preprocedural evaluation necessary to determine if a patient is a candidate for endovascular
repair, important intraprocedural considerations, and the necessary postprocedure follow-up
and surveillance. Finally, the current clinical experience with endovascular treatment of TAA and
traumatic thoracic aortic injury is specifically discussed.
DEVICES
Initial thoracic stent-graft procedures used homemade devices usually employing a combination
of Dacron polyester fiber and modified Z stents (9). These early grafts were rigid, requiring
large delivery systems (24- to 27-Fr sheaths) and often were difficult to deploy precisely due to
frictional forces created by the removal of the delivery sheath. Yet this initial experience led the
way to the development of several commercially available thoracic endoprosthesis that are less
rigid, lower in profile, and much easier to deploy precisely. Currently only one device has FDA
approval for use in the treatment of TAA: the TAG (W. L. Gore & Associates) was approved in
March 2005. Presently two other devices, the TALENT (AVE/Medtronic, Inc.) and the TX2
(Cook, Inc., Bloomington, IN), are undergoing clinical trials for FDA approval (Fig. 10-1).
The Gore TAG

The Gore device incorporates a flexible Nitinol skeleton lined with polytetrafluoroethylene
(PTFE) material (10). The Nitinol skeleton and PTFE lining confer radial and longitudinal
flexibility to the device. The proximal and distal ends of the graft are composed of PTFE-
covered crowns to improve contact with the aortic wall. It is delivered through a 20- to 24-Fr
sheath that is determined by the diameter graft required for treatment. Stentgraft diameters
range from 26 to 40 mm and available lengths are 10, 15, and 20 cm (10), with certain lengths
available only for certain diameters.
The Nitinol skeleton is laser-bonded to the PTFE material without the use of sutures and is
constrained with a PTFE sleeve. The original graft design incorporated two longitudinal Nitinol
wires (spine) to add radial strength to the graft.
Unfortunately, delayed spine fracture was noted with early experience and the manufacturer
voluntarily withdrew the device from the market and revised the design of the stent-graft. The
new design utilizes a new, more durable, multilayer PTFE cover, which adds greater longitudinal
strength and does not require spines (10).
FIGURE 10-1. Current thoracic stent-grafts that have finished enrollment in U.S. clinical
trials. A: Original Gore TAG Excluder device with longitudinal spine. B: Modified Gore TAG
currently marketed for repair of descending thoracic aortic aneurysms. C: Proximal
component of the two-piece Cook TX2 endograft system. D: Distal TX2 piece that fits
coaxially inside the proximal section. E: Talent thoracic endograft manufactured by
Medtronic.
Deployment is rapid using a ripcord mechanism that spans the entire length of the sheath.
Pulling the ripcord knob at the hub of the deployment sheath quickly releases the constraining
PTFE sleeve beginning at the middle of the device and simultaneously moving toward the
proximal and distal ends of the graft. This design allows for the device to be deployed against
the high arterial flow while limiting graft migration (10). After deployment, the proximal and
distal ends of the graft are gently molded to the aortic wall with a specially designed trilobed
silicone balloon (TAG Thoracic Excluder Balloon Catheter).
The Gore TAG device is the only FDA-approved stent-graft for the treatment of TAA (Fig. 10-
2). Beginning in 1999, 142 patients were treated in a prospective nonrandomized trial
conducted at 17 sites. Successful deployment of 237 devices in 139 patients was performed
from 1999 to 2001 (10). The overall survival rate and aneurysm-related survival rate at 2 years
were 75% and 97%, respectively. There were two perioperative deaths, one from a stroke and
one from a cardiac event. No ruptures were observed over 24 months and reported
complications included stroke (3.5%), paraplegia (3%), and wire fracture. Twenty wire
fractures in 19 patients were reported, with 18 (90%) occurring in the longitudinal spines. Thus,
Gore halted the trial and withdrew the product from the market. The product was redesigned
and a confirmatory trial was begun in 2003. This was a prospective nonrandomized trial
involving 11 investigational sites, with 51 patients enrolled (11). Early outcomes showed the
incidence of major adverse events to be 12%, compared to 70% in the control group (11).
Vascular complications were 6%, which was similar to the rate in the control group, and
decreased from the 1999 pivotal study, likely reflecting the increased awareness of the
potential complications from iliac access (11). No deaths or major device-related events were
reported at 30 days (11). The device gained FDA approval in March 2005.
The Medtronic Talent

The Medtronic Talent device incorporates a polyester fabric (Dacron) that is sewn onto
individual self-expanding Nitinol stents with braided polyester suture (12). The Nitinol stents are
independent of each other, which gives a certain amount of longitudinal flexibility to the device.
In addition, two longitudinal wires run the length of the graft to confer stabilization and support.
It is delivered through a 22- to 27-Fr sheath that is determined by the diameter graft required
for treatment. Stentgraft diameters range from 22 to 46 mm and available covered lengths
range from 112 to 116 mm (12).
The Talent device has an uncovered proximal portion that is either a Bare Spring (<24 mm) or a
Freeflo device (>24 mm) (12). This feature allows the proximal uncovered portion to be placed
across the origin of a great vessel, which can be helpful in cases where a short proximal neck
exists. If required, an uncovered distal portion is also available for placement of the distal graft
over the celiac trunk.
The stent-graft is deployed using a Coil Trac TDS delivery system. This is composed of a
conical tip, a blunt metal stopper proximal to the stent-graft, and the compressed device on a
delivery catheter. The device is compressed with an overlying transparent sheath. The graft is
positioned and the transparent sheath is pulled back to deploy the graft (Fig. 10-3). The
stopper maintains the position and prevents migration of the device as it is deployed. Previous
delivery systems had an integrated balloon on the proximal aspect of the delivery catheter. For
the ongoing VALOR (Vascular Talent Thoracic Stent-Graft System for the Treatment of TAAs)
trial, the delivery system was redesigned without the balloon to reduce the chances of kinking
(12). A separate Reliant (Medtronic, Inc., Minneapolis, MN) stent-graft balloon is now used
after deployment to mold the proximal and distal ends of the graft. The Medtronic VALOR trial,
a prospective, nonrandomized, multicenter trial evaluating the use of the Talent device for the
treatment of thoracic aortic disease, recently completed its enrollment. It consists of three
arms: the pivotal group, the registry group, and the high-risk group. The pivotal group contains
195 patients and the 1-year data are currently being accrued before presentation to the FDA
(13). The results of the 150 patients enrolled in the high-risk group were recently presented at
the 2005 Society of Vascular Surgery meeting (13). There was an initial procedural success
rate of 98%. The 30-day mortality rate was 8.4% and complications included stroke (8%),
paraplegia/paraparesis (5.5%), and endoleak (12%) at 30 days. The reported endoleak rate at
6 months was 10%. No ruptures, surgical conversions, device migrations, or graft thromboses
were reported.
The Cook TX2

The Cook (Cook, Inc., Bloomington, IN) device incorporates standard-thickness polyester fabric
(Dacron), which is sewn onto stainless-steel Gianturco Z stents with an ethibond (Ethicon, Inc.,
a Johnson & Johnson Company, Somerville, NJ) suture (14). The original TX1 device is a
single-component system, which has since given way to the TX2, a two-component device,
which requires deployment of two overlapping components regardless of aneurysm length. The
two-component system gives increased flexibility to the device. This allows the device to better
accommodate to the changes in aortic length and tortuosity both during the procedure and after
deployment due to aneurysm sac remodeling (14).
The TX2 proximal component contains multiple-covered Gianturco Z stents of which the most
proximal contains a series of 5-mm caudally arranged barbs that extend through the Dacron
fabric in a staggered fashion. The distal aspect of
the proximal component has no barbs and ends with a covered sealing stent. The TX2 distal
component has a covered proximal zone that should be overlapped with the proximal device by
at least two stents. The distal aspect of the stent employs an uncovered Gianturco Z stent with
cranially oriented, staggered 5-mm barbs that prevents proximal migration of the distal
component.
FIGURE 10-2. Contained rupture of the mid-descending thoracic aorta. A: Thoracic
aortogram shows aneurysm of the mid-descending aorta with linear tract projecting from
the apex of the sac. This represents a contained rupture of the aneurysm. B: Axial CT
scan through the lesion displays the protrusion of the process through the left posterior
ribs. C: Completion imaging confirms a good result, with no evidence of residual filling of
the aneurysm. Two Gore stent-grafts were required to repair the lesion because of a
mismatch in the diameters of the proximal and distal necks. D: CT scan performed less
than 24 hours after device insertion confirms only a trace of contrast medium from the
recent implant procedure within the aneurysm sac, without evidence of an endoleak or
change in the sac appearance from the precontrast images. Note that the lesion extends to
the chest wall, but there is less distortion of the posterior thorax after the procedure.
The delivery system for the TX1/TX2 is designed to allow for deployment of the entire covered
portions of the endograft while fixing the proximal and distal ends of the device to a central core
(14). This design allows the operator to deploy the device in a controlled, unrushed fashion
while still being able to reposition the device before final deployment of the endograft (release
of the proximal/distal ends). The device is delivered through a 20- or 22-Fr sheath dependent
on the diameter of the device that is used. Available device diameters range from 22 to 42 mm,
and available lengths range from 77 to 220 mm (14).
FIGURE 10-3. Stent-graft repair of distal aortic arch aneurysm. A: Left anterior oblique
aortogram with aneurysm involving the proximal descending thoracic aorta. The proximal
neck of the aneurysm required for anchoring the stent-graft involves the left subclavian
artery origin. B: Following surgical creation of a left carotid-to-subclavian bypass graft, a
Medtronic Talent thoracic stent-graft was placed over the left subclavian origin in a position
bridging the aneurysm sac. The aortogram after deployment of the endograft
demonstrates a good result, without evidence of an endoleak.
While the TX1 and TX2 is in commercial use in Canada, Europe, Asia and Australia, it is
currently undergoing a prospective, nonrandomized, multicenter phase II U.S. clinical trial to
access its safety and efficacy in the treatment of TAA in the hope of gaining FDA approval.
Individual institutions have published their results and they appear encouraging. Greenberg et
al. treated 100 patients with the TX1/TX2 for a variety of thoracic diseases from 1991 to 2001
(14). Their overall mortality and aneurysm-related mortality rates at 1 year were 17% and 14%,
respectively. Reported complications included stroke (3 of 100 patients) and
paraplegia/paraparesis (6 of 100 patients). In addition, endoleaks were detected in 8.5% and
6% at 30 days and 12 months, respectively, and migration of the proximal or distal component
was seen in 6% of patients. No ruptures were reported over a mean follow-up time of 14
months and sac regression at 12 and 24 months was 52% and 56%, respectively.
PREPROCEDURAL EVALUATION
Reviewing the patients that have under gone endovascular thoracic aortic repair, it is clear that
many of these patients were considered high risk for traditional open surgical repair. Indeed,
current recommendations reserve endovascular aortic repair for high-surgical-risk patients and
nonoperative candidates with anatomic features that are amenable to endovascular repair (15).
Yet, given the fact that emergent conversion to open surgical repair is a reality in any
endovascular procedure, the preprocedural evaluation should begin in a similar fashion to the
preoperative assessment performed before traditional surgical repair. This includes a careful
assessment of the individual's cardiac and pulmonary function and renal reserve and an overall
assessment of the patient's comorbidities and procedural risk.
Of utmost importance is full characterization of the lesion undergoing treatment. Careful
preprocedure planning is vital to limiting complications and in obtaining a successful
endovascular repair. While catheter-based angiography was historically the gold standard for
assessing the thoracic aorta for endovascular repair (15), most centers now rely on computed
tomography (CT) angiography and/or magnetic resonance (MR) angiography for assessing the
thoracic aorta prior to endovascular repair (15, 16, 17). Comprehensive images of the thoracic
aorta can be obtained by reconstructing CT or MR imaging (MRI) three-dimensional (3D) data
sets into multiplanar reformations, curved planar reformations, maximum intensity projections,
and 3D volume-rendered images (15,16).
Preprocedural imaging is needed to size the aorta and measure the extent of the disease to
select the appropriate diameter and length of device needed. Endovascular stents are often
oversized by 10% to 20% to ensure sufficient radial force for adequate fixation and to prevent
stent migration (15).
Various anatomical features must be assessed when evaluating a patient for thoracic
endovascular repair. Evaluation of the diseased aorta in relation to the subclavian artery and
celiac trunk must be assessed for suitable device fixation sites (landing zones or necks)
(15,18). This is necessary for proper device-aortic wall fixation and formation of a tight
circumferential seal (15). A proximal and distal nondiseased neck of 15 to 25 mm is necessary
to ensure adequate fixation and seal of the device (15,18). In the case of a short proximal neck
many investigators will overcome this by prophylactically covering the left subclavian artery
(18,19). In addition to neck length, evaluation of the neck shape and angulation is important.
Conical necks, overly angulated necks, or necks with a large calcium or thrombus burden may
make fixation difficult (15).
Evaluation of the iliofemoral access sites is another important consideration of the
preprocedural evaluation. The obligatory large sheaths necessary for device deployment
require relatively large vessels for delivery of the device (15,19). Additionally, tortuous access
vessels and excessively calcified vessels present a dilemma when trying to pass the large,
relatively rigid devices (15). Small access vessels may necessitate a retroperitoneal exposure
and creation of a surgical conduit to the iliac artery or aorta (15,16). In addition, tortuosity of
the access vessels or aorta can often be overcome with stiff guidewires that will straighten the
vessels out and allow passage of the endoprosthesis (16). It is important to have a grasp of
the anatomical landscape of each patient undergoing endovascular aortic repair to plan for
difficult anatomy, which may make endovascular repair difficult.
DEPLOYMENT
An interdisciplinary approach to thoracic endovascular repair combines the catheter-based skills
of interventional radiologists and the surgical skills of vascular or cardiovascular surgeons.
Procedures are performed in an operating room equipped with fluoroscopy or an operating-
room-compatible angiography suite (20, 21, 22). High-quality fluoroscopic imaging with
available digital subtraction capabilities, overlay imaging technique, road mapping, and last
image hold are desirable if not imperative (20,21,23). In addition, adjuncts to help in precise
placement such as trans-esophageal echocardiography (TEE) (24) and intravascular ultrasound
have been employed.
While the majority of thoracic endograft procedures are done under general anesthesia,
multiple novel anesthetic approaches including epidural anesthesia, combined single-shot spinal
anesthesia and epidural anesthesia, continuous spinal anesthesia, and local anesthesia have
been described (25, 26, 27, 28, 29). Patients are prepared and draped in the normal sterile
fashion (23) so that emergent open conversion can be performed if necessary. In this regard
proper anesthesia, nursing, and technical personnel as well as access to cardiopulmonary
bypass should be available if required (20).
Vascular access, through a femoral artery cutdown, or through a surgically placed conduit is
then obtained (21, 22, 23, 24). Through percutaneous access into the contralateral femoral
artery or a brachial artery, a marker pigtail catheter is advanced into the thoracic aorta and
used for intraprocedural thoracic aortography for precise graft placement. An advantage of
high-quality 3D preprocedural imaging is the ability to ascertain the exact obliquity, proximal
neck, and proximal landing zone for precise deployment. Following access, the patient is
heparinized and prophylactic antibiotics are administered (21,23).
The endoprosthesis is then advanced into the thoracic aorta over a superstiff wire and
positioned in the area intended for exclusion. A predeployment aortogram is obtained to confirm
precise positioning. Prior to deployment the mean arterial pressure is pharmacologically
lowered to between 55 and 80 mm Hg (22, 23, 24). In addition, certain groups have advocated
the use of adenosine-induced transient cardiac asystole (30, 31, 32, 33) and the induction of
ventricular fibrillation (34) prior to deployment to reduce the pressure place on the device by
aortic pulsations. While this does reduce the risk of prosthetic migration, this is not commonly
needed with the new commercially available devices. The endograft is deployed and a repeat
aortogram is obtained to confirm adequate position.
If multiple devices are used, proper overlapping of the prostheses is required to create an
adequate seal and to prevent separation. If the devices are of differing diameters, the smaller
device is deployed first and the bigger device is placed coaxially within the smaller graft. If
multiple devices of the same diameter are required, they are usually placed proximally to
distally. After final deployment an angioplasty balloon may be used to mold, readjust, or expand
the stent-graft (24). As discussed earlier, the commercially available devices often come with
an angioplasty balloon, depending on the specific device being used. A final postdeployment
aortogram is then performed to verify device position and to exclude perigraft leaks. The
endovascular access devices are removed and the arterial access sites are repaired.
Protamine sulfate is then administered for anticoagulation reversal.
FOLLOW-UP
Immediately following endovascular thoracic aortic repair patients will spend 24 to 48 hours in
the Intensive Care Unit. This is dependent on when the patient is extubated and deemed to be
hemodynamically stable. Interestingly, in the case of aneurysmal disease, the mean arterial
blood pressure is often kept relatively elevated, which is a departure from the traditional
postoperative management of conventional thoracic aortic repair. If successfully excluded, the
aneurysm sac should not be exposed to systemic arterial blood pressure and so an elevated
mean arterial blood pressure should not pose a threat for rupture. In fact, the elevated mean
arterial blood pressure helps maintain adequate spinal perfusion to help guard against spinal
cord ischemia. Indeed, hemodynamic stability is vital in the perioperative period to guard
against this dreaded complication (35). Spinal cord ischemia is discussed in more detail in the
following section.
While various postprocedure imaging protocols for surveillance after endovascular aortic repair
have been described (36, 37, 38, 39), it is clear that postprocedural monitoring with noninvasive
imaging is crucial for the follow-up of this patient population. Imaging should evaluate for graft
patency, evidence of prosthetic migration, changes in aortic morphology, and endoleaks.
Surveillance can be performed with CT angiography at intervals that are often center specific.
One protocol would be CT angiography at 1, 6, and 12 months, then yearly thereafter. Imaging
at 3 months postprocedure can also be obtained or reserved for patients with documented
endoleaks on the 1-month scan. Additionally, some centers obtain initial CT imaging within 1 to
3 days immediately following endovascular repair (39). This must be weighed against the
patient's baseline renal function, given the fact that intravenous contrast will be used so soon
after receiving the contrast required during endovascular repair. A safe alternative in patients
with renal insufficiency is MR angiography, although the metallic components of the
endoprosthesis do present challenges for adequate MR angiographic imaging.
An inexpensive imaging evaluation of the thoracic endoprosthesis can be obtained with plain
radiography. Chest radiographs allow evaluation for device migration, kinking, or collapse. AP
and lateral chest radiographs are especially helpful in patients who have prolonged hospital
stays secondary to concomitant conditions or injuries as with trauma patients. In addition to
imaging follow-up, some centers are investigating new surveillance strategies using implantable
pressure sensors (Fig. 10-4).
FIGURE 10-4. Large saccular thoracic aortic aneurysm of the distal arch managed by
endovascular stentgraft placement and followed by remote pressure sensor surveillance.
A: Aortogram illustrates a large aneurysm of the proximal descending thoracic aorta with a
proximal neck that has a smaller diameter than the diameter of the distal neck. B: Prior to
deployment of the proximal and smaller diameter stentgraft, a CardioMems detachable
pressure sensor is introduced into the aneurysm sac on its delivery catheter (arrow). C:
After insertion of the sensor and two Gore TAG endografts, a completion aortogram
shows a good result, with positioning of the proximal device across the left subclavian
artery origin and no endoleak of contrast medium into the aneurysm. D: Pressure tracings
from the sensor in the sac recorded before (gray) and after (black) placement of the
endografts confirm a good outcome, with a marked drop in the aneurysm pressure
occurring over the interval.
COMPLICATIONS
A variety of complications associated with endovascular repair of the thoracic aorta has been
described as experience with the procedure has grown. These complications can be related to
the endoprosthetic device, the procedure itself, or various medical comorbidities associated
with this relatively complicated patient population.
Endoleaks represent the most common device-related complication. Endoleaks are defined as
the persistence of blood flow outside the lumen of the endoluminal graft but within the aneurysm
sac or the adjacent vascular segment being treated by the graft (40,41). Endoleak rates of
between 17% and 29% have been reported (38,42, 43, 44). If there is flow around the proximal
or distal stent-graft attachment site, it is known as a Type I endoleak. When blood flows around
the graft and into the aneurysmal sac or adjacent vascular segment via retrograde flow through
vessels excluded by the device, it is known as a Type II endoleak. Typically, in the case of the
thoracic aorta, this is secondary to intercostals arteries that have been excluded by the
endoluminal device. Structural failures, including fractures, holes within the device, and
separations between multiple devices, have been shown to allow for leakage into the excluded
area of the aorta and are known as Type III endoleaks. Type IV endoleaks are the result of
graft wall porosity and are identified at the time of implantation. This is usually seen as a blush
of contrast during the postdeployment aortogram while patients are still fully anticoagulated.
This usually resolves with anticoagulation reversal. Finally, a Type V endoleak is related to
endotension. Endotension is when an aneurysm sac continues to grow or there is increased
tension on the aneurysm sac with no evidence of an endoleak.
Interestingly, endoleaks are less common after TAA repair then AAA repair (15). Additionally,
the distribution of endoleaks is different in the thoracic aorta than in the abdominal aorta. Unlike
the abdominal aorta, where Type II endoleaks are more common, Type I endoleaks are more
commonly seen in the thoracic aorta (15,45). Type I endoleaks are considered more serious
than Type 2 endoleaks and are often intervened on with a combination of balloon angioplasty,
stenting, stentgraft extension, embolization, or, if necessary, open repair (15). Other device-
related complications that have been reported include device migration, kinking, and fracture
(15,38,45,46). Device migration and kinking have mostly been identified with older homemade
devices and grafts with unsupported midgraft segments (15). Stent fracture has been noted in
older devices, including the original design of the Gore TAG device. Migration, kinking, and
fracture may be influenced by the rather pronounced changes in aortic size and morphology
months to years after endovascular thoracic aortic repair.
Procedural-related complications that have been reported include spinal cord ischemia, stroke,
and access site complications. Paraplegia is a known complication of open surgical repair often
related to the time of aortic cross clamping. Surgical paraplegia rates range from 1.5% to 19%
(42). Unfortunately, spinal cord ischemia resulting in paraplegia is still problematic after
endovascular thoracic aortic repair. This is likely secondary to the covering of critical intercostal
arteries during stent-graft deployment, which may lead to their subsequent thrombosis (42). In
addition, delayed spinal cord ischemia hours to months after the procedure can be seen,
possibly due to subsequent thrombosis of covered intercostals arteries or transient episodes of
hypotension (42). The risk of paraplegia after endovascular repair is less than for open repair,
with rates ranging from 0% to 12% (38,42,43,47, 48, 49). The risk of paraplegia increases
when lengthy areas of the thoracic aortic or critical intercostals arteries (T7-T11) are excluded
(42). Prophylactic cerebrospinal fluid (CSF) drainage to alleviate spinal cord pressure has been
recommended by several groups in patients deemed to be at high risk for ischemia (45,47) and
in patients with delayed onset of ischemic symptoms after stent-graft deployment (47,50).
Tiesenhausen et al. recommend prophylactic CSF drainage in patients undergoing long segment
exclusion of the thoracic aorta (50). In addition, Czermak et al. have also recommended
prophylactic CSF drainage in patients who previously have undergone surgical repair of an AAA
(45).
Stroke is a complication seen since the earliest experience with thoracic endografting. Indeed,
Dake et al. reported a stroke rate of 7% with early first-generation stent-grafts of the thoracic
aorta (51). This is likely the result of the large, bulky devices being manipulated near the aortic
arch and great vessels. This is especially worrisome in patients with a large atherosclerotic
burden at the level of the arch. As operator experience has grown and new commercial devices
have become available the stroke rate has dropped but has not disappeared completely.
Finally, a large number of complications related to the access site for thoracic endovascular
repair have been noted. Again, this is related to the advancement of large devices into the
common femoral artery or common iliac artery in a patient population that often has
concomitant atherosclerotic disease. In addition, the relatively higher proportion of women seen
with TAA generally means that overall, smaller access vessels are being utilized. Injuries from
access artery dissection to frank iliofemoral disruption have been described (22,42). Hopefully
fewer access site complications will be seen as operator experience continues to improve and
as further refinements in device design are implemented.
Patients undergoing endovascular thoracic aortic repair often present with multiple medical
problems, and while endovascular repair offers a less invasive alternative to traditional open
surgical repair, periprocedural complications are inevitable. Various complications including
respiratory failure, myocardial ischemia, cardiac arrhythmias, septicemia, and end organ
ischemia/infarction secondary to embolic events have been described (22,42). Renal
complications have also been reported. Scharrer-Pamler et al. reported a renal complication
rate of 4.4% (42). The relatively low rate of renal insufficiency seen in endovascular aortic
repair can be attributed to the constant perfusion of the kidney parenchyma and the judicious
use of contrast medium during the procedure.
APPLICATIONS
Endoluminal stent-grafting has been employed as a minimally invasive treatment alternative to
traditional surgical repair for a number of diseases of the thoracic aorta. This section examines
its use in the treatment of two specific disease processes: TAAs and traumatic aortic injury.
Thoracic Aortic Aneurysm

Epidemiology and Natural History
Aneurysmal disease of the thoracic aorta, although relatively rare, is the most common disease
of the thoracic aorta and is the 13th leading cause of death in the United States (52). It is
defined as a focal, localized area of aortic dilatation that is at least 1.5 times larger then the
normal-caliber thoracic aorta and involves all three layers of the aortic wall (4,53,55). The
incidence of TAA ranges from 5 to 10.4 per 100,000 personyears (1,4,52,53,55). Although less
common than its counterpart in the abdominal aorta, TAA is being seen with increasing
frequency (55). This is likely secondary to improved diagnostic tools such as echocardiography
and noninvasive cross-sectional imaging (4,52). Older studies reported TAA to be more
prevalent among the male population (56) but newer reports appear to demonstrate a female
predominance (4), unlike AAA. Interestingly women appear to present at an older age and are
at an increased risk for rupture as well (4,56, 57, 58).
Aneurysms are often classified by their location, shape, and etiology. One quarter of all aortic
aneurysmal disease occurs in the thoracic aorta (55,56). Of these, 40% to 50% are located in
the descending thoracic aorta, 50% are located in the ascending thoracic aorta, and up to 10%
involve the aortic arch (1,52). In addition, up to 25% of patients who have an aneurysm of the
thoracic aorta will have a concomitant AAA (55,56). Aneurysms are often described as fusiform
(concentric radial dilatation) or saccular (eccentric radial dilatation), with the majority of TAAs
being fusiform (1). Saccular aneurysms are less common, are often associated with infection,
and are more commonly located in the ascending aorta or aortic arch.
There is a broad spectrum of etiologies for the formation of TAAs. It has been the belief that
most aneurysms of the descending thoracic aorta are the result of atherosclerosis
(1,4,52,54,56). These aneurysms have been termed degenerative, as they are thought to be
the result of a late degenerative stage of atherosclerosis (1). Yet there is significant
controversy over whether atherosclerosis is an underlying cause of TAA
(52,54,59). Given that similar risk factors exist for both disease processes the relationship
between atherosclerosis and aortic aneurysm formation may be more of an association then
causal (52,59). Other etiologies for aneurysms of the descending thoracic aorta include trauma,
mycotic (infectious) and inflammatory aortitis, postoperative pseudoaneurysms, cystic medial
necrosis, and chronic dissection (1,52). Common ascending TAA etiologic factors include
chronic Type A dissection and cystic medial necrosis secondary to Marfan's syndrome and
Ehlers-Danlos syndrome (52). Less common etiologic factors in ascending TAA include
poststenotic dilatation secondary to aortic stenosis, trauma, infectious or inflammatory aortitis,
and syphilis (52). In addition, recent evidence points to genetic and familial causes of aortic
aneurysm formation (52,59). Indeed, Kontusari et al. (60) characterized the first genetic
mutation relating to aneurysm formation in a non-Marfan family and Biddinger et al. (61)
confirmed the familial aggregation of TAA. More recently, Coady et al., at the Yale Center for
Thoracic Aortic Disease, demonstrated a genetic predisposition to the development of TAA in
patients with no evidence of collagen vascular disease (62).
A majority of patients with TAA are asymptomatic and are diagnosed incidentally. Symptoms
develop as the aneurysm enlarges and causes compression of adjacent structures (56).
Symptoms include vague chest, back, flank, and abdominal pain, which can increase in severity
as the aneurysm enlarges (1,56). Sudden onset of pain can be seen with rapid aneurysm
expansion or rupture (56). As the aneurysm enlarges, it can invade and compress adjacent
structures, resulting in hoarseness from compression of the recurrent laryngeal nerve,
hemidiaphragmatic paralysis from compression of the phrenic nerve, cough or respiratory
symptoms from tracheal deviation, or hemoptysis from bronchial or pulmonary parenchyma
erosion (56). Dysphagia and hematemesis resulting from esophageal compression and erosion
and even neurologic deficits from erosion into the spine or chest wall can occur (56).
The natural history of aneurysms is progressive expansion and eventual rupture: an often
catastrophic event (1,56). In fact, rupture is reported as the most common cause of death in
patients with TAA (1,56,63,64). Despite 41% of patients arriving to the hospital alive,
Johansson et al. reported a mortality rate for ruptured TAAs of 97% (65). Reported 5-year
survival rates for patients with untreated TAAs range from 13% to 64% (1,52 55 57),with
rupture being responsible for the majority of deaths. Cardiovascular disease is also responsible
for a significant percentage of mortality among this patient population and is the second most
common cause of death in patients with TAA (4, 56, 63).
Clearly the most important risk factor for aortic rupture when evaluating patients with TAA is the
size of the aneurysmal sac (4,57,58,66). A significant increase in risk for aortic rupture has
been reported for aneurysms >6.0 cm (52,57,66,67). The Yale Center for Thoracic Aortic
Disease reviewed more than 600 patients with thoracic aortic pathology and found that the
median aortic size in patients who developed aortic rupture or dissection was 6.0 cm in the
ascending thoracic aorta and 7.2 cm in the descending thoracic aorta (52,57). Indeed, the Yale
group found that TAAs >6.0 cm had a 27-fold increase in rupture compared to aneurysms <4.0
cm (57). Studies have shown that certain patient populations are at increased risk for rupture
including women, those with dissection associated with TAA, and those with collagen vascular
disease (4,52,55, 56, 57, 58,63,64). Other risk factors for rupture include chronic obstructive
pulmonary disease, age, and smoking.
Conventional Repair
Given that the natural history of aneurysms is one of progressive aneurysm sac dilatation and
eventual rupture, patients that are suitable operative candidates should be considered for
elective repair. Conventional operative repair requires either median sternotomy, left
posterolateral thoractomy, or both, full systemic heparinization, aortic cross clamping,
establishment of proximal and distal aortic control, and resection of the aneurysmal portion of
the aorta with interposition of a synthetic Dacron graft (1,68,69). Surgical repair of TAA often
requires partial or full cardiopulmonary bypass and adjunctive measures for end-organ
protection such as CSF drainage to protect against spinal cord ischemia (35,68). Reported 30-
day mortality following operative repair ranges from 5% to 12% (1,5,6,68, 69, 70, 71, 72, 73),
with an associated 5-year actuarial survival rate of 70% to 79% and a 10-year actuarial survival
rate of 40% to 49%.
Although elective surgery for TAA has improved over recent years, resulting in decreased
mortality significant morbidity still remains. Complications associated with open surgical repair
include paraplegia/paraparesis, stroke, renal insufficiency, and cardiopulmonary failure. Despite
multiple intraoperative adjuncts to protect spinal cord profusion, various authors have reported
paraplegia/paralysis rates in the range of 4.5% to 16.5% (68, 69, 70, 71, 72,74). The reported
incidence of postoperative renal failure ranges from 5.9% to 18% (68,69,72).
Operative repair for asymptomatic TAAs is recommended when the aneurysm diameter is twice
the size of an adjacent normal-caliber segment of aorta or >6.0 cm (1). In addition, aneurysms
of any size that become symptomatic require intervention (1,75) and smaller aneurysms that
demonstrate rapid growth are often treated more aggressively, with operative repair at smaller
sizes (75). The Yale group recommends intervening on ascending TAAs at 55 mm and on
descending TAAs at 65 mm (66). In addition, the Yale group recommends earlier intervention at
50 mm in patients with collagen vascular disease and aneurysms associated with dissection.
Smaller, asymptomatic TAAs are watched and followed with serial noninvasive imaging every 6
to 12 months.
Endovascular Therapy
TAA is the most commonly treated lesion of the thoracic aorta. Currently, endovascular repair
of descending TAAs is the most widely used application of stent-grafting and the application for
which the most clinical data are available. The goal of endovascular repair of TAA is to
decrease aneurysm sac pressure by excluding the sac from aortic flow. This allows thrombosis,
remodeling, and eventual stabilization of the aneurysm sac, with possible sac shrinkage over
time.
The feasibility and safety of endovascular TAA repair were demonstrated in early studies in
high-risk surgical patients. Selection of patients early in the experience of endovascular TAA
repair focused on individuals thought to be at high surgical risk and deemed to have favorable
anatomic features amenable to stent-graft repair. As experience has grown, the application of
stent-graft technology to lower-risk surgical patients has expanded. The next section gives a
brief review of the current literature, describing the technical success, mortality, and
complications of endovascular repair of TAA.
Results
Single-center, small to midsized case series dominate the literature on endovascular therapy of
descending TAA. Midterm and long-term data are just now being reported. A summary of
published studies on endovascular repair of the descending TAA is given in Table 10-1.
Continued monitoring of the earliest patient populations from initial feasibility studies is just now
yielding midterm to long-term data and provides the longest follow-up available on patients who
have undergone endovascular descending TAA repair. While these studies utilized rigid,
homemade first-generation devices, the results of
initial studies were promising and prompted further investigation (9,38,51). From 1992 through
1997 a prospective uncontrolled clinical trial, involving 103 high-risk patients with descending
TAA who underwent endovascular treatment, was performed at the Stanford University Medical
Center (51). The study utilized homemade endografts made of Dacron fiber woven onto a
Gianturco Z stent. The initial short-term outcomes included technical success in endograft
placement of 100%, complete aneurysm thrombosis in 84%, periprocedural mortality of 9%, a
paraplegia/paraparesis rate of 3%, a stroke rate of 7%, myocardial infarction in 2%,
respiratory insufficiency in 12%, and a primary endoleak rate of 24%. The relatively high
incidence of stroke was a surprise to the investigators but was most likely caused by
manipulation of the relatively rigid delivery system in the aortic arch employed by the early
homemade devices.
TABLE 10-1 SUMMARY OF PUBLISHED DATA ON ENDOVASCULAR REPAIR

OF DESCENDING THORACIC AORTIC ANEURYSMS
Mean
Study
follow- Technical 30-day Long-term
Study size Paraplegia Stroke Endoleak
up success mortality survival
(N)
(mo)
Ehrlich et
10 100% 0% 0% 10% 20%
al. (1998)
Graben-
woger et 21 100% 0% 0% 9.5% 14.3%
al. (2000)
Greenberg
et al. 25 15.4 12% 0% 20% 12%
(2000)
Temudom
et al. 14 5.5 78% 7.1% 0% 14% 14.3%
(2000)
Heijmen et
28 21 96% 0% 0% 0% 96.4% 29%
al. (2002)
Bergeron
et al. 33 24 N/A 0% 3% 9% 10% 0%
(2003)
Lepore et
21 12 100% 5% 9.5% 10% 76.2% 19%
al. (2003)
Marin et
94 15.4 94.6% 25%
al. (2003)
Ouriel et 81.6%
31 6 6.5% 12.9% 45.2%
al. (2003) (at 1 yr)
Schoder
96.1%
et al. 28 22.7 100% 0% 3.6% 0% 25%
(at 1 yr)
(2003)
Sunder-
Plassmann
45 21 2.2% 0% 6.7% 22.2%
et al.
(2003)
90%
Bell et al. (between
249 87% 4% 2.8% 10% 10.6%
(2004) 1 and 12
mo)
Makaroun
75% (at
et al. 142 24 98% 3% 4% 1.5% 4%
2 yr)
(2005)
Periodic updates on the outcomes of this initial patient cohort have been published (9,20,
24,51,76, 77, 78, 79) and most recently it has been revisited with a mean follow-up of 4.5
years and a maximal follow-up of 10 years (79). Actuarial survival rates at 1, 5, and 8 years
were 82%, 49%, and 27%, respectively. Interestingly, life expectancy was significantly higher
for operable patients versus nonoperable patients with an actuarial survival rate of 93% versus
74% at 1 year, 78% versus 31% at 5 years, and 38% versus 28% at 8 years. Death in the
inoperable patients was mostly secondary to comorbid conditions unrelated to their TAA.
Overall, 5.4% of late deaths could be attributed to TAA rupture, all of which occurred in patients
with a previously documented endoleak. Secondary endoleaks were identified in 21% of
patientsthe majority of which were Type I and Type III endoleaks. These results demonstrate
the promise of endovascular treatment of descending TAA while pointing out some of the
limitations of early experiences. The homemade devices used in early series must be taken into
consideration when assessing the potential outcomes possible with new commercially
manufactured devices.
Reduced adverse outcomes have been achieved with current commercially available devices.
Czerny et al. recently reported results from 54 patients with TAA treated with the Gore
Excluder and Medtronic Talent device (80). Patients were followed for 38 months (mean) and
results included a primary technical success rate of 94.4% with an in-hospital mortality rate of
3.7% (both procedure/device related). Only three (5.6%) primary Type I endoleaks were seen
but a secondary endoleak rate of 28.9% was reported (of which 15.4% were Type I and Type
III endoleaks). No neurologic events were reported.
Perhaps the largest multicenter series comes from the combined experience of the UK and
EUROSTAR Thoracic Endograft Registries. Between 1997 and 2003, 249 patients with TAA
were treated, both electively and emergently (81). Primary technical success was achieved in
87% of cases, with an overall 30-day mortality of 10%. Comparing 30-day mortality between
patients treated emergently and those treated electively, it is not surprising that a higher
mortality was seen among the emergent population (28% vs. 5.3%). Aneurysm-related death
was seen in only 2.1% of patients, and 80% of patients had satisfactory findings on follow-up
CT scans at 12 months. Adverse events included paraplegia/paraparesis (4%), stroke (2.8%),
and a primary endoleak rate of 9.2%.
Although multicenter prospective randomized trials are needed to compare surgical versus
endovascular therapy for descending TAA, single-center case series have been reported
(82,83). Najibi et al. treated 19 patients with the Gore Excluder and Medtronic Talent device
and compared his results with those for a historic nonrandomized cohort of 10 patients who had
undergone open descending TAA repair (82). Technically successful endovascular deployment
was seen in 95% of cases, with no evidence of primary endoleak or secondary endoleak (up
to12 months' mean follow-up). Mortality rates at 12-month mean follow-up were lower for the
endovascular group (10.5%) than for the surgical group (30%), and a significantly higher
morbidity was seen among the conventionally treated patients (50% vs. 26%). Both operative
time (155 vs. 256 minutes) and overall length of stay (6.3 vs. 16.3 days) was significantly
reduced among the patients treated endovascularly. Neither patient cohort has any cases of
stroke or paraplegia. A similar trend is seen in the results reported by Ehrlich et al. (83). A
substantial decrease in 30-day mortality was seen with the endovascular group (31% vs. 10%).
In addition, decreased mean length of intervention (150 minutes vs. 320 minutes), length of
hospital stay (6 days vs. 10 days), and rate of spinal cord ischemia (0% vs. 12%) were seen
among the endovascular group. Despite these promising results, a true multicenter randomized
prospective trial is needed to make more accurate comparisons among the two treatment
paradigms.
The ever-increasing worldwide experience in endovascular repair of descending TAAs has led
to an accumulation of data that points to a consensual pattern of outcomes. The periprocedural
mortality associated with this technique ranges from 0% to 14.3% (10,21,23,38,44,81,84, 85,
86, 87, 88, 89), which is comparable to the perioperative mortality associated with conventional
surgical repair (1,5,6,68, 69, 70, 71, 72, 73). As most of the patient cohorts who underwent
endovascular repair in these studies were nonoperable or high-risk surgical candidates, one
would expect only improved periprocedural mortality rates, as this treatment alternative is
further applied in good to average surgical candidates. In addition, further improvements in
results can be expected as devices are further refined and operator experience continues to
grow (90). Still, the long-term benefits and durability of thoracic endovascular devices are still
unknowns and continued research and long-term patient follow-up are required to answer these
questions. Finally, randomized prospective trials are needed to ascertain the applicability and
recommendations for use in younger, lower-risk patients.
Thoracic Aortic Injury

Epidemiology and Natural History
Traumatic aortic injury is often the result of blunt trauma that results in a transverse tear in the
wall of the aorta (91). A spectrum of injury can be seen that ranges from a partial tear of the
intima to complete aortic transaction (91). The lesions are often the result of injuries associated
with sudden deceleration. This is most commonly seen with high-speed automotive accidents
(91,92). In fact, acute thoracic injuries result in 10% to 20% of all fatalities associated with
motor vehicular accidents (93). Other, less common causes include pedestrian accidents, falls,
and plane crashes (91,92). The predominant pathophysiologic mechanism leading to acute
aortic injury relates to the mobility of the ascending aorta compared to the more fixed
descending aorta and heart (91,92). Thus, sudden deceleration creates shear forces that result
in tears in the thoracic aorta. Given the immobility of the descending aorta at the level of the
ligamentum arteriosum, it is not surprising that this is the most common area of thoracic aorta
injury. Other areas of relative immobility include the aortic root and the distal descending
thoracic aorta at the level of the diaphragm. Parmley et al. report that thoracic aortic injury is
seen at the aortic isthmus in 50% to 71% of cases, in the ascending aorta in 18% of cases,
and in the descending aorta in 14% of cases (94).
Thoracic aortic injury is often a catastrophic even that leads to patient demise. Anywhere from
80% to 90% of patients suffering thoracic aortic injury die before reaching the hospital (91,94,
95, 96). In addition, those who do make it to the hospital have a 30% mortality rate at 6 hours
and a 40% mortality rate at 24 hours (93).
Given the sobering mortality rates associated with this catastrophic injury, prompt diagnosis
and treatment are a necessity. Unfortunately this injury is often difficult to diagnose (92). These
patients often present with a multitude of concomitant injuries that may mask their aortic injury.
While the finding of a widened mediastinum, tracheal or nasogastric tube deviation, or left
bronchus depression on a chest radiograph may raise suspicion (92), some authors have
questioned its sensitivity (97). As fast multislice CT angiography becomes more accessible, it
will be interesting to see how this affects the outcomes in this patient group.
In 1% to 2% of patients the diagnosis of thoracic aortic injury is not made and the patients
survive to develop a chronic traumatic pseudoaneurysm (94). Chronic traumatic
pseudoaneurysms are usually localized, calcified, saccular aneurysms that are located distal to
the left subclavian artery (98). Unfortunately, like other disease processes of the thoracic aorta,
progressive expansion and eventual rupture of chronic traumatic pseudoaneurysms are a risk.
Finkelmeier et al. reported on 413 cases of chronic traumatic pseudoaneurysm (99). Of the
15% of patients who did not undergo surgical repair, one third died of aortic rupture.
Conventional Repair
The standard surgical treatment for thoracic aortic injury involves left thoractomy and aortic
cross clamping with repair of the damaged aortic segment or placement of an interposition
graft with cardiopulmonary bypass (100). Repair is often complicated by the multiple other
injuries inherent in this patient population. Systemic heparinization and proper patient positioning
are often problematic due to concomitant neurologic and orthopedic injuries. Although outcomes
are improved over those with nonsurgical management, surgical management is associated
with high morbidity and mortality rates. Studies report an operative repair mortality rate that
ranges from 10% to 32% (101, 102, 103), with the rate of paraplegia ranging from 8.7% to
26.1%.
Symptomatic and expanding chronic traumatic pseudoaneurysms obligate open surgical repair
(99,104). Finkelmeier et al. reported an operative morality rate of 4.6% and a neurological
complication rate of 2.8% (1.4% spinal cord injury and 1.4% stroke). Interestingly Katsumata et
al. recommend continued observation for asymptomatic chronic traumatic pseudoaneurysms
that demonstrate a uniform thick layer of calcification with no radiographic evidence of
expansion (104).
Endovascular repair presents an exciting minimally invasive treatment alternative for thoracic
aortic injury. Given the multiple injuries often encountered in traumatically injured patients stent-
grafting offers a treatment modality that can be performed quickly, before or after addressing
other life-threatening injuries. In addition, endovascular repair can often be performed acutely
without destabilizing the patient while avoiding cardiopulmonary bypass and systemic
heparinization and the comorbidities associated with them.
As stated earlier, traumatic aortic lesions are often focal and located in the proximal descending
aorta. Thus, thoracic aortic injury often presents a favorable anatomic target for endovascular
repair (Fig. 10-5). Given the fact that most lesions begin at the aortic isthmus, a 15-mm landing
zone from the left subclavian artery is often difficult to obtain. Thus, most reported cases
employ intentional coverage of the left subclavian artery with expectant management. This
approach is generally well tolerated in this patient population.
Limited clinical experience with endovascular repair for thoracic aortic injury currently exists,
and most studies are small, retrospective, single-institution case series. The results of 13
studies are summarized in Table 10-2 (105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115,
116, 117). Demers et al. reported on 15 cases of stent-graft placement for thoracic aortic
injury, with a mean follow-up period of 55 months (109). A technical success rate of 100% was
achieved, with only one periprocedural mortality that was unrelated to the procedure or the
patient's thoracic aortic disease. No cases of paraplegia were reported and only two Type I
endoleaks were seen. The reported 1- and 6-year actuarial survival rates were 93% and 85%,
respectively. Similarly, Dunham et al. achieved a technical success rate of 100%, with no
reported cases of paraplegia, in 16 patients treated endovascularly for thoracic aortic injury,
with a 10.7-month mean follow-up period (113). One postprocedural mortality was seen that
was related to the patients comorbid injuries and one stroke was seen in a patient who had a
concomitant preoperative traumatic carotid artery
dissection. No graft-related complications, such as endoleak, were identified.
FIGURE 10-5. Traumatic aortic injury following a motor vehicle accident. A: An abnormal
circular collection of contrast medium is noted adjacent to the lesser curve of the aortic
arch in a patient complaining of chest pain after a car accident. B: A Gore TAG device was
placed over the lesion along the inferior aspect of the distal arch. The completion
aortogram shows a good result with no endoleak. The left subclavian artery was
intentionally covered in an effort to ensure a circumferential seal between the device and
the aortic wall. Persistent antegrade flow was evident within the subclavian artery, although
fluoroscopically the flow was observed to be sluggish. CT imaging at the time of hospital
discharge documented a left subclavian steal phenomenon with occlusion of the proximal
subclavian artery.
The low rate of paraplegia seen in these studies is likely related to the proximal, relatively focal
segment of aorta that usually requires exclusion in patients with thoracic aortic injury.
Additionally, the majority of endoleaks encountered in this patient population were proximal
Type I endoleaks, high-lighting the fact that obtaining a proximal seal may be more difficult in
this often young patient population due to a tight radius of curvature of the aortic arch.
TABLE 10-2 SUMMARY OF PUBLISHED DATA ON ENDOVASCULAR

REPAIR OF TRAUMATIC AORTIC INJURY
Mean
Study Technical Procedural
Study follow-up Paraplegia Stroke Endoleak
size(N) success mortality
(mo)
Rucat et al.
4 11 100% 0% 0% 0% 0%
(2001)
Czermak et 5%
6 17.4 83% 0% 0% 0%
al. (2002) (1)
Lachat et al. 16.6%

12 17 100% 0% 0% 8% (1)
(2002) (2)
Orend et al. 9.1% 18.2%

11 14 100% 0% 0%
(2002) (1) (2)
Thompson et
5 20.2 100% 0% 0% 0% 0%
al. (2002)
Karmy-Jones 27.3% 36.4%

11 2-24 100% 0% 0%
et al. (2003) (3) (4)
Marty-Ane et 11.1%
9 4-20 100% 0% 0% 0%
al. (2003) (1)
Orford et al. 11.1%

9 21 100% 0% 0% 0%
(2003) (1)
Demers et al. 6.7% (13.3)

15 55 100% 0% 0%
(2004) (1) 2
Dunham et al. 6.3% 6.3%

16 10.7 100% 0% 0%
(2004) (1) (1)
Kato et al. 16.7%

6 6 100% 0% 0% 0%
(2004) (1)
Ott et al.
6 24 100% 0% 0% 0% 0%
(2004)
Richeux et al.
16 32 100% 0% 0% 0% 0%
(2004)
Examined as a whole the preliminary studies reveal a technical success rate of 98.7%, a
mortality rate of 6.3%, a paraplegia rate of 0%, and an endoleak rate of 8.2% (105, 106, 107,
108, 109, 110, 111, 112, 113, 114, 115, 116, 117). These results compare favorably to the
results of conventional operative repair. Amabile et al. compared conventional surgical repair to
endovascular repair for traumatic thoracic aortic rupture in
20 patients (118). Eleven patients underwent surgical repair, compared to nine endovascularly
treated patients. There was an operative mortality of 9.1%, compared to a procedural mortality
of 0%. Neither cohort experienced a case of paraplegia. Endovascular technical success was
seen in 100% of patients and complete aneurysm thrombosis was seen in all cases with a
15.1-month mean follow-up. Rousseau et al. compared 35 surgically treated patients to 29
endovascularly treated patients for thoracic aortic injury (119). The mortality and paraplegia
rates in 28 patients treated with emergent surgery were 21% and 7%, respectively, compared
to 0% mortality and paraplegia in the endovascularly treated cohort. Complete exclusion of the
pseudoaneurysm sac was seen in all endovascularly treated patients.
NEW HORIZONS
The short-term and midterm data have substantiated the great promise that endovascular
thoracic aortic repair holds for the treatment of thoracic aortic disease. Yet the experience with
endovascular repair has also demonstrated the limitations inherent with current devices.
Although novel adjuncts to address difficult access anatomy, such as small or tortuous iliac
arteries, are discussed earlier in this chapter, this does not address the difficult problem of
thoracic aortic disease that is close to or involves the aortic arch and great vessels. Various
innovative surgical and devise-based strategies are being explored to extend the applicability of
endovascular repair to the ascending thoracic aorta and the aortic arch.
Numerous surgical-based strategies to treat lesions close to or involving the great vessels have
been employed. While intentional coverage of the left subclavian artery with expectant
management (19,120, 121, 122) is now a frequently accepted technique to obtain an adequate
proximal neck, this is not sufficient to treat lesions that involve the origin of the left subclavian
artery or are located more proximally within the thoracic aorta. Surgical ligation with or without
left subclavian-to-left carotid artery bypass or coil embolization of the origin of the left
subclavian artery (120) can be performed in lesions that involve the origin of the left subclavian
artery to prevent endoleak. In addition, carotid-to-carotid artery bypass has been performed to
allow an adequate neck for endovascular repair of more proximal lesions (123).
Diffuse thoracic aortic disease involving all three segments of the thoracic aorta (ascending,
arch, descending) is another manifestation of thoracic aortic disease that proves difficult for
endovascular management. Conventionally, this is treated with an elephant trunk procedure
(124,125), which involves a large, two-stage operation. In the first stage a median sternotomy
is performed and the ascending thoracic aorta is replaced with a synthetic graft, which is left
dangling in the descending aorta. The second stage of the procedure is performed a few
months later via a left thoracotomy where the distal end of the elephant trunk is used to repair
the distal descending thoracic aorta. Thus, conventional therapy requires two major operations
to tackle this difficult disease process. A novel approach to decreasing the morbidity and
mortality of this procedure with an endoluminally placed device has been reported
(120,126,127). This involves placing an endovascular prosthesis within the distal end of the
elephant trunk, which obviates the need for a second operation. A novel operation recently
performed at the University of Virginia for the treatment of a diffuse TAA that involved the distal
ascending thoracic aorta employed a median sternotomy for synthetic bypass of all three great
vessels from the proximal ascending thoracic aorta with stent-graft placement from an
antegrade approach at the time of bypass. Finally, innovative combined surgical and
endovascular approaches in treating the 25% of patients with concomitant TAA and AAA have
been reported. This involves simultaneous abdominal aortic replacement and thoracic aortic
stent-graft repair (128). Additionally, endovascular stent-graft repair of both the abdominal and
the thoracic aorta has been reported (129).
The limitations of current endovascular prosthetic devices often revolve around inadequate
landing zones and unacceptable coverage of critical aortic branch vessels. Device-based
strategies to extend endovascular applicability to such lesions indeed represent the next horizon
in endovascular aortic repair. Branched prosthetic devices to accommodate flow in the great
vessels and visceral vessels have been designed (130,131). In addition, fenestrated grafts in
the abdominal aorta have been described by Park et al. (132). While no reports of fenestrated
thoracic stent-grafts have been reported, the adaptation of this technology to thoracic devices
seems plausible. In fact, McWilliams et al. have used intraprocedural fenestration of a modified
thoracic stent-graft to maintain flow to the left subclavian artery (133). These innovative device
designs remind us that we are still in the very early stages of endovascular thoracic aortic
repair but also portend the promise of increased applicability to more complex thoracic aortic
lesions in the years ahead.
SUMMARY
The advent of endovascular stent-graft technology has created an exciting new treatment
paradigm for various thoracic aortic diseases. The promising results from initial feasibility
studies for the treatment of TAA in high-risk surgical patients has led operators to expand the
use of stent-graft technology to various thoracic aortic diseases including traumatic aortic injury.
While prospective randomized clinical trials and further evaluation of the long-term data from
existing series are needed to access the long-term durability of these prosthetic devices, the
initial and midterm results are encouraging. Further clinical trials comparing conventional
surgical outcomes to endovascularly treated patients for a variety of aortic pathologies are
needed to compare the two treatment modalities as well as to ascertain the role of this new
technology in healthier, more favorable surgical candidates.
Still, the available data suggest that, at least in the short term, transluminally placed thoracic
aortic stent-grafts provide a minimally invasive therapeutic alternative for a variety of aortic
pathologies that compliment traditional surgical repair.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 11 - Abdominal Aortic
Aneurysm Stent-Grafting
Chapter 11
Abdominal Aortic Aneurysm Stent-Grafting
Kenneth R. Thomson
Peter Y. Milne
Ashu Jhamb
Stuart M. Lyon
Abdominal aortic aneurysms (AAAs) make up 95% of all aneurysms. The primary etiology
appears to be atherosclerosis. Often there is a family history and, in many cases, a close
association with hypertension, smoking, and chronic obstructive airways disease. The
male:female incidence is 4:1, with a peak incidence in the eighth and ninth decades. It is a
leading cause of death in the United States and the 10th most common cause of mortality for
males >65 years old. The incidence before age 60 is very low, and this has raised the idea of
population screening. A longitudinal population screening study of 41,000 males in Western
Australia showed no definite benefit from ultrasound screening to detect AAA. There was,
however, some benefit in selected groups of men suitable for endografts, between 65 and 75
years of age, provided that the rate of open operation was low (1). In contrast, a study from
the United Kingdom that screened men once, at 62 years, showed a detection rate of 15%,
which enabled longitudinal follow-up and a reduced rate of rupture (2).
The abdominal aorta has a normal transverse diameter of about 2 cm and an AAA is
considered to exist when the diameter is 3 cm. Unlike mycotic aneurysms or the dilatation
associated with aortic dissection, an AAA is a true aneurysm. It most commonly involves the
infrarenal aorta but may extend into the iliac arteries and also involve the thoracic aorta.
Aneurysms may vary widely in external shape and there is commonly a moderate to large
amount of mural thrombus in the aneurysm; as a result, conventional angiography may not
reveal the true state of the aorta unless the wall and/or the thrombus is calcified. Distal limb
embolization of thrombus from an AAA either spontaneously or during catheterization is
common, and is sometimes how the AAA presents clinically.
Rupture of an aneurysm may occur at any size but the incidence is 5% per year when the
aneurysm is 4 cm in diameter. The rupture rate rises exponentially with increasing size, to
10% per year at 5-cm diameter and to >75% per year at >9-cm diameter. Conventional open
surgery is usually not considered until the aneurysm reaches 4.5 to 5 cm in maximum external
diameter. Earlier surgery may be considered if there is rapid enlargement of an existing
aneurysm or if there are signs suggesting impending rupture, such as abdominal pain or
inflammatory change around the AAA on imaging studies. Rupture of the aneurysm is fatal
unless urgent correction is performed, and even with emergent surgery, the mortality of a
conventional open operation for aortic rupture is of the order of 30%, largely because of the
older age and comorbidities of this patient group. This compares with an elective nonrupture
operative mortality of about 4.0%
In an attempt to assess the operative risk, a Glasgow Aneurysm Score (GAS) has been
proposed. This is calculated as [risk score = (age in years) + (7 for myocardial disease) + (10
for cerebrovascular disease) + (14 for renal disease)]. It has been shown to be predictive of
postoperative death, severe postoperative complications (including myocardial infarction and
stroke), and long-term survival following both conventional open aneurysm repair (3) and
endovascular aortic repair (EVAR) (4). Biancari and co-workers found in their series of patients
from the EUROSTAR registry that the median GAS was 78.8 (interquartile range, 71.9-86.4;
mean, 79.2). Tertile 30-day mortality rates were 1.1% for patients with a GAS 74.4, 2.1% for
those with a score between 74.4 and 83.6, and 5.3% for patients with a score >83.6 (p
0.001).
The exclusion of an AAA by placement of an intraluminal stent-anchored Dacron prosthetic graft
retrograde from the femoral artery is vastly different from the open conventional Dacron repair.
Although stent-grafts were performed in Russia in the 1980s, Parodi and co-workers first
described their technique in 1991 (5). Since then, stent-grafts for abdominal aortic aneurysms
have moved into mainstream treatment and have radically altered the relationship among
vascular surgeons, interventional radiologists, and interventional cardiologists. The first
endovascular aortic graft performed in the United States was reported in May 1995 (6).
Since that time there have been several generations of endovascular devices but most consist
of a metallic stent skeleton covered with a material designed to seal the aneurysm. In most
cases the grafts must be customized to fit the patient, and although modular grafts are now
available, not all patients are suitable to have an EVAR because of a short infrarenal neck,
excessive tortuosity, or severely calcified small-caliber iliac arteries. The major limitation of
EVAR is the need to have continued follow-up of the patient to exclude late failure of the graft
and the development of endoleaks. Endoleaks are classified (Table 11-1) according to the site
of the leak, and in the presence of an enlarging sac, a leak is considered a risk factor for aortic
rupture. However, in the event of rupture a previous EVAR may reduce the degree of
hemodynamic change and operative mortality compared to patients with no prior intervention
(7). Long-term follow-up of EVAR is now available, and there is a significant benefit in terms of
operative mortality and morbidity compared to conventional surgical AAA repair. In the relevant
studies this occurred despite the fact that the EVAR patients tended to be older and have more
comorbidities, and despite the higher need for secondary procedures in the endovascular group
(8,9).
More recently the method of endovascular repair for acute aortic aneurysm rupture has been
extended, as some institutions stock sufficient device components to enable immediate acute
repair. Early endovascular repair of a ruptured aneurysm may reduce the incidence of
abdominal compartment syndrome. The major advantage is the management of otherwise
difficult challenges such as scarred and herniated abdominal walls and stomas from previous
surgery, which would otherwise create long and tedious approaches to an exsanguinating
patient.
TABLE 11-1 CLASSIFICATION OF ENDOLEAKS
I. Leakage at the anchoring/sealing points of the stent-graft
a. Proximal attachment
b. Midgraft (body limb junction)
c. Distal attachment
II. Collateral vessel perfusion of the aneurysm sac
a. Only one branch vessel identified
b. More than one branch vessel identifieda
III. Leakage due to defects in the stent-graft composition
IV. Leakage due to graft material porosity
V. Endotension where no site of leak is identified
a Although there are almost always multiple vessels, they cannot usually be identified
on the CT scan.
ASSESSMENT OF THE ANEURYSM

Clinical examination will detect many aneurysms >4 cm in diameter, except in obese patients or
when the aneurysm involves a localized segment of aorta. In reality, though, detection of the
AAA is often serendipitous during computed tomography (CT) or ultrasound of the abdomen for
other reasons. Ultrasound is inadequate for proper measurement of AAA for EVAR, as this
requires determination of the character of the neck of the aneurysm, angulation of the
aneurysm, and state of the iliac arteries. Angiography with a graduated catheter was once a
prerequisite for assessment for endografting, but preoperative planning is now largely
performed by multidetector row CT with three-dimensional (3D) and maximum intensity
projection (MIP) reconstructions. Recent advances in the CT scan technology from single-row
detectors to multirow detectors have changed the acceptability of CT as the only preoperative
evaluation imaging (Fig. 11-1).
FIGURE 11-1. Maximum intensity projection (MIP) of an AAA. CT scanners with

multidetector rows have vastly improved the image quality to the point where angiography
prior to the EVAR is hardly necessary. A: The original CT scanners produced
reconstructions with misregistration artifacts. B: A 16-slice CT thick slab MIP image that is
free of artifacts.
TABLE 11-2 CT PARAMETERS FOR ASSESSMENT OF AAA FOR

ENDOGRAFT
Helical scan from diaphragm to inguinal ligament
DFOV 30 cm with standard protocol
Postcontrast (100 ml of 37% iodinated nonionic contrast at 4 ml/sec)
SmartPrep or 30- to 35-sec delay with baseline scan at first slice of the series
Soft tissue algorithm

1-mm axial reconstructions from superior mesenteric artery to start of aneurysm
2.5-mm axial reconstructions through aneurysm to femoral artery
MPVR with length and diameter measurements
3D displays including scale
MIP with spine edited: 6 projections
SSD with spine included: 6 projections
Images should include table position and a scale.
In a very tortuous aorta orthogonal slices should be imaged.
Note: DFOV, defined field of view; MPVR, multi-planar volume reconstruction; MIP,
maximum intensity projection; SSD, shaded surface display.
A typical CT protocol for evaluation of AAA is listed in Table 11-2. The aim of measurement is to
determine, first, if an endovascular solution is feasible and, if so, what size and length of
endograft is required. Modular bifurcated endografts have made the selection of the correct
overall length much less
problematic, as they can be overlapped to create an adjustable overall length in situ. The most
critical measurement is the length of the upper neck. Ideally the neck should be at least 15 mm
long, 30 mm in diameter, cylindrical in shape, free of plaque and thrombus, and not
excessively tortuous (Fig. 11-2). Ideal patients are hard to find, and probably the only crucial
measurement is the length of the neck, as this is the zone where the endograft seals the
opening to the aneurysm. It has been estimated that between 25% and 50% of patients with
AAA are not suitable for an EVAR.
FIGURE 11-2. Assessment of the neck of the aneurysm. The ideal neck is >15 mm long,
cylindrical in profile, and free of atheromatous plaque or calcium. Most necks have some
degree of angulation, particularly in the AP direction. For this reason caudal angulation is
required during angiography to achieve orthogonal projections.
FIGURE 11-3. Unsuitability for EVAR. A common cause of unsuitability for EVAR is mural
thrombus or atheroma in the neck of the aneurysm. As the aorta responds to the presence
of an endograft, mural thrombus or atheroma may remodel and produce an endoleak. A:
The axial slice just below the renal arteries shows an almost-circumferential thrombus or
atheroma. B: The MIP reconstruction shows that the neck is abnormal right to the level of
the renal arteries. Note that the measurement cursor has been incorrectly placed in the
right renal artery orifice. This is a common error, especially on axial slices.
In an Australian cohort study with the Zenith endograft (Cook Inc.), 68% of patients did not
meet the manufacturer's recommended suitability guidelines (10). The most ignored guideline
was the neck length, and breaching this guideline resulted in a fourfold increase in endoleaks.
Regardless, however, primary and secondary aneurysm exclusion rates were still 87% and
94%, respectively, in the Australian cohort. The risk of failure of the EVAR procedure needs to
be carefully considered if the vendor's measurement guidelines are ignored or extended by the
operator (Fig. 11-3). In a recent study the mortality of early (30-day) conversion from EVAR to
an open repair was 22% (11).
One faces a problem in balancing the risk of an open conversion later with the risk of an
immediate open repair when a pre-existing comorbid condition, such as cardiac disease, makes
the patient unsuitable for open repair. No randomized study has been done to eliminate this
selection bias. Of the authors' 400 cases of EVAR, 15% would have been refused open repair
because of comorbidity. This riddle will remain unsolved forever, as patient demand for less
invasive technologies is the driving force for endograft repair and minimally invasive procedures.
Catheter angiography is now used primarily in patients with tortuous aortae or in those where
other procedures such as lumbar or iliac embolization are required because of advances in CT
angiography (Fig. 11-4). Embolization of large lumbar arteries is considered to reduce the risk
of Type II endoleaks, and there is some evidence that embolization of a patent inferior
mesenteric artery prior to placement of an endograft is also associated with a lower incidence
of endoleak and a more rapid decrease in aneurysm size (12). While a recent study suggested
that accessory renal arteries do not contribute to the incidence of endoleaks after EVAR (13),
our experience is that any large artery may do so by providing cross flow into
the excluded aneurysm sac (Fig. 11-5). When the aneurysm sac has a low thrombus load, there
appears to be more opportunity for connections to persist across the excluded sac between
lumbar arteries and the inferior mesenteric artery. (14) When the internal iliac origin is involved
in the aneurysm, the endograft is usually extended into the external iliac artery and the internal
iliac artery embolized to prevent backfilling of the aneurysm. More recently it has been realized
that buttock claudication is common and often disabling after internal iliac artery occlusion.
Extensive embolization of the distal branches of the internal iliac arteries may be catastrophic
(Fig. 11-6).
FIGURE 11-4. Patent inferior mesenteric artery. A patent inferior mesenteric artery is more
likely to remain patent when the aneurysm sac contains little thrombus. A: In this example
the origin of the inferior mesenteric artery is visible and a large lumbar artery is also
present on the posterior aspect of the sac. B: The inferior mesenteric artery is more easily
demonstrated on a thick-slab MIP projection after the EVAR when the endoleak is
established.
FIGURE 11-5. Accessory renal artery causing endoleak. In this example an endoleak
developed between an accessory renal artery and a patent inferior mesenteric artery even
though the aneurysm sac contained a large amount of thrombus. These arteries were
accessed by direct puncture angiography of the sac. The inferior mesenteric artery has
been occluded by coils.
FIGURE 11-6. Buttock necrosis following atheroembolism. This patient succumbed to
complications of his EVAR due to extensive atheroemboli into his internal iliac arteries.
Excessive manipulation of the endograft was probably the cause of this event. There are
large patches of skin necrosis visible.
FIGURE 11-7. Placement of an iliac limb into an ectatic right iliac artery. An ectatic iliac
artery may be used as an end point for flared endografts but there is an increased risk of
aneurysm rupture or development of a Type 1 endoleak. In this example there is also
severe external iliac artery tortuosity. Correction of this endoleak required extension of the
endograft limb into the right external iliac artery.
Placement of a flared endograft into a dilated internal iliac artery is possible but this may be
associated with a risk of late rupture of the common iliac artery, particularly if the vessel is
aneurysmal rather than dilated (Fig. 11-7). A better solution is placement of a second
bifurcation of the graft to preserve the common iliac artery bifurcation. This requires more time
and catheter expertise and, most importantly, a reasonable diameter of the external iliac artery.
One of the limitations of current endograft technology is the need for room to assemble the
components of a branched endograft (Fig. 11-8).
Endografts are usually oversized by 10% to ensure a secure fixation at the neck. For most off-
the-shelf endografts, the range of sizes that are available limits the neck diameter to 30 mm.
In follow-up CT scans of large-diameter endografts it is not uncommon to find evidence of a
mural thrombus within the body of the endograft. This thrombus may alter position from one CT
examination to another probably in response to changes in flow as the aneurysm changes
shape as it reduces in size (Fig. 11-9).
Custom hand-crafted grafts are available for almost any aneurysm including fenestrated models
for aneurysms with no infrarenal neck. These fenestrated grafts require careful positioning of
the fenestrations and secondary stenting or endografting of some of the vessels supplied
through the fenestrations.
In Asian populations particularly, the iliac arteries are narrow in caliber in comparison to
European populations. If the iliac vessels are calcified as well as slender and tortuous, it may
be impossible to insert a device without damage to the iliac artery. Devices larger in caliber
than the external iliac artery may require surgical access by means of a temporary
retroperitoneal common iliac Dacron graft.
Measurement and planning of the final placement of the endograft should allow for a final
position as close to the lowest renal artery as possible. Experience from open repair of AAA is
that the entire segment of infrarenal aorta is likely to become aneurysmal with time. For
inexperienced operators anxious about covering a renal artery, it is tempting to release the graft
well away from the renal arteries in cases where the infrarenal neck permits. If a bifurcated
endograft has been measured to the renal arteries, the result will be a problem of access to the
contralateral limb, as it will open lower than planned.
FIGURE 11-8. Assembly room. In planning an endograft procedure it is important to ensure
that there is room to assemble the components of a branched endograft. In this example
the aortic portion of the aneurysm is quite narrow. For most endografts the bifurcation
requires a minimum diameter to encompass two 12-mm-diameter limbs. The right iliac
aneurysm has been excluded by extending the right limb into the external iliac artery.
FIGURE 11-9. Mural thrombus within an endograft. If a very large-diameter endograft is
used, it is not uncommon to find evidence of a mural thrombus forming within the endograft
at follow-up. This indicates that the diameter of the endograft is larger than optimal for
laminar flow. There are no data regarding late outcome of these large-diameter
endografts. In this case, however, the aneurysm has ruptured and the thrombus indicates a
more sinister problem. There is extensive hemorrhage in the right renal fossa and
retroperitoneum.
TABLE 11-3 PLANNING MEASUREMENTS
Diameters (external margins)
Aortic diameter at the level of the upper renal artery (D1)

Aortic diameter at the midportion of the infrarenal neck (D2)
Aortic diameter at the lowest portion of the neck (D3)
Maximum aortic dimension (D4)
Lumen diameter at aortic bifurcation (D5)
Minimum common iliac dimension
Maximum right common iliac artery (D6R)
Maximum left common iliac artery (D6L)
Maximum right external iliac artery (D7R)
Maximum left external iliac artery (D7L)
Angulation
Aorta above renal arteries to neck
Neck to aneurysm long axis
Right iliac artery to aneurysm long axis
Left iliac artery to aneurysm long axis
Lengths (midline length)
Lowest renal artery to start of aneurysm (L1)
Lowest renal artery to aortic bifurcation (L2)
Aortic bifurcation to right common iliac bifurcation (L3R)
Aortic bifurcation to left common iliac bifurcation (L3L)

Check the plan
Diameter of neck of endograft
Diameter of ipsilateral iliac limb at end zone
Diameter of contralateral iliac limb at end zone
Desired length of endograft body section
Desired length of endograft limb (ipsilateral)
Desired length of endograft limb (contralateral)
Side of insertion of body of endograft
The exact series of measurements varies from vendor to vendor but the measurements, as
reported in Table 11-3, are usually measured from a contrast-enhanced CT scan with or without
an angiogram with a calibrated catheter. Most CT scanners have specific software for AAA
measurement. A suitable CT protocol is reported in Table 11-2. Normally the neck diameter is
taken as the average or the larger of the three measurements at the neck. Specialized 3D
modeling programs are available at significant cost to show the graft in position in the aneurysm
to help in planning the procedure.
The measurement is typically performed by a CT technologist and the vascular surgeon or
interventional radiologist selects an endograft based on the measurements and the look of the
CT reconstructions. In the case of customized endografts it is usually necessary for the CT
information to be presented in a specified format to the vendor for validation of the
measurements and construction of the endograft.
Traps in measurement are many and it is important to ensure that they are consistent within
each center. It is also important to allow for the placement and access to the contralateral limb
in the case of a bifurcated endograft. If the endograft is planned with a body too long for the
aneurysm sac, it will result in both limbs opening into a single common iliac artery.
PATIENT SELECTION
Patients selected for endograft repair should have the same indications as for a surgical repair.
In practice, patients fall into one of three groups: those well suited to an endovascular repair,
those best suited to an open repair, and those for whom neither open surgery nor EVAR is
possible. In an otherwise healthy patient with low risk factors and an AAA considered easy by
surgery and EVAR, both are obviously possible and some vascular surgeons consider an open
operation to be quicker and more durable without the added risks of contrast induced renal
failure, radiation, and endoleaks associated with EVAR. Recent randomized studies in the
United Kingdom compared EVAR with open surgery for AAA (15) and, subsequently in patients
unfit for open surgery, EVAR with supportive medical therapy (16). The findings of these studies
were that there was no long-term benefit of EVAR compared to open surgery and no difference
in aneurysm-related mortality for EVAR compared to no treatment at all. This may be related to
the considerable medical comorbidity in this group of patients. The 30-day mortality for EVAR
was 9%, which is twice the operative mortality in Australia for open surgery for AAA. The
experience in Australia is that there is a significant mortality and morbidity benefit in the short
term but that in the long term the benefit of EVAR is lost. This is primarily due to endoleaks.
One difference in Australia compared to the rest of the world is the long-standing commercial
presence of customized devices that, unlike some other types of endograft, have stood the test
of time.
Although generally the patients undergoing endograft repair have smaller maximum aneurysm
dimensions, there has been no benefit shown by treatment of small (4-cm) aneurysms. The
EUROSTAR collaborators reported a benefit for treatment of aneurysms between 4.0 and 5.4
cm in maximum diameter compared to those >6.5 cm maximum diameter. The differences were
much less marked for the intermediate group with a maximum diameter between 5.5 and 6.5
cm (17). An aneurysm >5 cm in maximum diameter or one that is rapidly enlarging or causing
abdominal pain is the usual indication for repair.
Those patients who are unable to tolerate conventional open surgery have a high mortality if an
endovascular repair fails during the procedure or within 30 days. Some causes of such failure
are inability to deploy the endograft due to tortuosity of the iliac vessels or the aneurysm itself,
failure to obtain exclusion of the aneurysm with a large endoleak, and rupture of the aneurysm
or the iliac arteries during deployment.
Modular devices such as the Cook Zenith Flex composite graft (Cook Inc.) are three-part
bifurcated endografts designed for extreme tortuosity and for patients with small-caliber iliac
arteries (Fig. 11-10).
SELECTION OF AN APPROPRIATE DEVICE

In the abdominal aorta a bifurcated endograft that extends from the renal arteries into the iliac
arteries is almost always required. Early models of endografts were straight aortic tubes or
aorto-uni-iliac devices and required occlusion of the contralateral common iliac artery and a
femorofemoral cross over Dacron graft. However, bifurcated endografts are now considered
standard.
The proximal fixation of an endograft is one of the most critical considerations, and while all
endografts employ graft expansion as a fixation method, some devices provide additional bare
stents that extend proximally across the renal arteries with or without hooks and barbs to
provide additional resistance to migration (Fig. 11-11). These cross-renal devices have not
been associated with significant increase in renal dysfunction and most of the observed renal
dysfunction after endograft insertion for AAA is probably due to iodinated contrast (18).
Endograft systems with fixation not solely dependent on expansile force have proved to have a
lower rate of migration and Type I endoleak. The closer to the renal arteries an endograft seal
is placed, the less likely a Type I endoleak is to occur (19).
A Type I endoleak is a failure of the endograft to isolate the aneurysm sac, which remains
subject to the same pressure that existed prior to the endograft. If the iliac outflow is sealed by
the limbs of the graft without achieving proximal closure, there may be even higher stress on
the wall of the aneurysm sac.
FIGURE 11-10. Composite endografts. Composite endografts have a two-part body

section that allows placement of either the upper end or the bifurcated end first. This
provides extreme flexibility of endograft placement and is an essential feature of a
fenestrated Zenith endograft (Cook Inc., Bloomington, IN.) In this example the lower end of
the upper body section has been released to allow catheterization of each renal artery
through fenestrations in the endograft. Contrast has been injected into the right renal artery
and a 6-Fr sheath is situated across the left renal orifice. Once the renal arteries are
securely sealed to the endograft, the lower body section and the iliac limbs are inserted.
FIGURE 11-11. Above renal artery fixation. Some endografts are designed to provide
fixation of the endograft above the point of sealing of the neck of the aneurysm. The Zenith
endograft (Cook Inc., Bloomington, IN) employs this method. The suprarenal stents are
uncovered and are only released from the top section of the delivery device after the body
section is open and the contralateral limb has been catheterized. This provides great
control in placement of the endograft.
With most devices, the first deployment step is release of the cranial portion of the endograft at
the level of the renal arteries. The Zenith and Trivascular endografts, however, have a
restraining device at the cranial end that allows a measure of adjustment after the endograft is
released. When the aneurysm neck is short and tortuous the ability to delay neck sealing until
most of the endograft is deployed is a significant benefit. However, excessive movement of the
partially deployed endograft may increase the possibility of emboli from the luminal thrombus
and atheromatous plaque within the aneurysm. The ability to provide adjustment of the
endograft is necessary if a fenestrated endograft is selected. A fenestrated endograft is one in
which there are apertures in the Dacron fabric of the endograft to allow access to major
branches such as renal or superior mesenteric arteries (Fig. 11-12).
Other design features associated with better outcomes are fully stented endografts with higher
columnar support and those with a high resistance to kinking or limb extension dislocation.
Limbs of bifurcated grafts without stent support required further intervention to prevent
thrombosis or kinking in 40% of cases in the EVT phase II trial (20), with the need for
placement of additional self-expanding stents in the limbs. Excessive tortuosity of the iliac
arteries is associated with limb occlusion from kinking as well as embolism from excessive
manipulation. It is now recognized that the endograft has a tendency to conform to the major
curvature of the aneurysm. This has been a factor in separation of limb sections from the main
body of an endograft (Fig. 11-13).
FIGURE 11-12. Fenestrated endograft. A fenestrated endograft is a custom-made device
with apertures in the endograft fabric to accommodate branch vessels, usually one or both
renal arteries. In this example there are apertures for both renal arteries and the superior
mesenteric artery. The endograft is fixed in position by stents placed in each renal artery
as shown.
FIGURE 11-13. Limb separation. Long iliac limbs are prone to separation from the body of
the graft as the aneurysm contracts post-endograft placement. In this example one of the
endograft limbs has completely separated, causing a massive Type 1 endoleak. The free
limb lies in the aneurysm sac and the limb that is still connected has occluded due to a kink
at the limb/body junction.
Selection of an endograft is a current problem in the United States, where the number of U.S.
Food and Drug Administration (FDA)-approved grafts is still limited compared to Europe and
Australia. In 2004 more than three fourths of the patients with an AAA of 5.0 cm, seen at a
tertiary referral center, were morphologically not suitable for endograft repair using two
currently approved bifurcated endografts (21). The main reasons for exclusion were aneurysm
angulation and diameters outside the range of manufactured and commercially available
endografts. The authors, however, find that more than 90% of referred patients are suitable for
EVAR, ignoring some of the contraindications for use of an endoluminal device, and the
resulting successful rate of exclusion of the aneurysm in our personal series of 400 procedures
is >90%. In Australia, where there is ready access to locally manufactured Zenith grafts (Cook
Inc.) in both ready-made and customized configurations, it is not surprising that these grafts
have the largest share of the market.
The recognition that occlusion of the internal iliac artery is a cause of significant morbidity from
buttock claudication has led to placement of endografts in ectatic iliac arteries with satisfactory
outcomes (22) even though there is a theoretical risk of rupture of the ectatic iliac segment.
Postprocedure assessment should include the external iliac artery for this reason. When the
iliac arteries are tortuous, heavily calcified, or narrow in caliber and an EVAR is planned, it is
prudent to have a plan prior to any possible rupture so that an additional endograft extension
can be placed immediately. In our experience of iliac artery ruptures, it is not immediately
apparent either clinically or angiographically until the major portion of the EVAR is completed.
This is partly because the delivery device tamponades the area of leakage and partly because
the adventitia of the vessel may contain the hemorrhage for some time (Fig. 11-14).
Coil occlusion of the internal iliac artery is also associated with buttock claudication, particularly
if the coils are placed distally in the internal iliac artery (23). A recent development is the iliac
bifurcated endograft, which provides a branch of the iliac limb to supply the internal iliac artery.
This device is a forerunner of similar branched endografts for use in the arch of the aorta and to
treat thoracoabdominal aneurysms (24,25). Preservation of the internal iliac artery reduces the
problem of buttock claudication but does not necessarily prevent embolism during deployment
of the branched device.
FIGURE 11-14. Iliac artery rupture. If it is recognized in time, a leaking iliac artery can be
repaired with an appropriately sized endograft extension. Off-the-shelf balloon expanded
endografts are usually too narrow in caliber to seal a ruptured iliac artery and the leak
itself may not be very obvious angiographically unless it is catastrophic. In this example a
large-caliber Jo-Graft (Abbott Vascular, USA) was placed in the common iliac artery but
this did not completely seal the point of rupture (arrow). A better alternative would have
been to extend the original endograft with an extension limb piece but none was available.
The need for a percutaneous device is less important now that it is recognized how diseased
the common femoral artery is in the group of patients with AAA and how low the morbidity of a
femoral cutdown procedure is, particularly if an oblique incision is used (26,27). Percutaneous
placement of the contralateral limb is commonly performed as it is usually 18 Fr or less in size.
A variety of suture closure devices have been used to obtain haemostasis (28).
Good results of endografts for aortic transection (29) have been used to extend the use of
endografts for leaking AAA. This has the potential to significantly reduce the mortality from
ruptured AAA but requires an off-the-shelf endograft system. Such a system is used in
Melbourne, Australia, for thoracic aortic rupture but the range of sizes required for AAA makes
this area more problematic. At some centers aorto-uni-iliac devices are held in stock for this
purpose.
DEPLOYMENT OF THE ENDOGRAFT

The method of EVAR is relatively straightforward in a wellselected patient. The generic
procedure for a bifurcated endograft is used here as an example. Each manufacturer provides
detailed instructions for use of its endograft and provides training specific to the device.
The access sites are prepared, and if required, the common femoral artery is surgically
exposed on one or both sides. An angiographic catheter is used to perform an angiogram to
confirm the position of the lowest renal artery (renal position) and the planned site of
deployment is marked. Where there
is angulation of the aneurysm neck, an orthogonal projection should be used. This usually
requires a few degrees of cranial angulation of the imaging C-arm in the AP view (Fig. 11-15).
A second (iliac position) angiogram is made to identify the level of the internal iliac artery
origin. This usually requires a degree of caudal tilt of the imaging C-arm. These positions can
be stored on most angiography units for quick repositioning of the imaging C-arm.
FIGURE 11-15. Aortic angulation. A lateral MIP projection will demonstrate clearly the
anterior angulation of the aneurysm neck. This degree of cranial angulation is required at
angiography to obtain orthogonal projections and to provide a true image of the neck
length. In this example the bare stents at the upper end of the endograft reach to the level
of the superior mesenteric artery.
The position of the endograft in the delivery device is checked and the body section of the
device is inserted up the iliac artery that is least tortuous and of the largest diameter to the
level of the renal arteries where the endograft is deployed. The imaging C-arm and patient
should be in the renal position at the site of the first angiogram
If a bifurcated system is being used, the markers to indicate the position of the contralateral
limb should be positioned to the correct side before the device is deployed. The body section is
deployed, and once the contralateral limb is accessible, it is catheterized from the contralateral
common femoral artery and the limb section deployed. For this deployment the patient and the
imaging C-arm should be in the second iliac position. With the imaging C-arm and the patient
in the same position, the ipsilateral iliac extension endograft is inserted and deployed if this is
required. Finally, the endograft sealing zones and junction points are expanded fully using a low-
pressure, high-volume balloon and angiography performed to confirm exclusion of the aneurysm
sac from the circulation. The access points are then closed surgically or by use of a closure
device.
Despite some manufacturers' claims to the contrary, no radiologist believes that, in the
abdomen or other thick body parts, a mobile image intensifier is as good as a fixed
angiographic unit. However, usually for reasons of control and the remote possibility of a need
for open conversion, some vascular surgeons still perform EVAR in an operating theater
environment. Gradually the environment in the operating theater is changing to include high-
quality fixed fluoroscopy/angiography units or angiography suites are changing to become true
operating theater environments. Whether these changes are economic or necessary is dubious.
In some cases it relates to who wishes to control the performance of EVAR in their
environment.
In our series three acute conversions and one 6-hour postprocedure conversion occurred from
1995 to 2003. One acute conversion in 1994 was required for rupture of the common iliac
artery during the procedure and a second rupture occurred at the common iliac artery origin
during a procedure in 2005. Both conversions were performed in the angiography suite.
Because the environment for the authors has always been in close proximity to an operating
room with anaesthesia support, no morbidity related to angiography suite use has been
recorded.
Apart from the imaging quality, the next most critical issues are familiarity with the device and
technical skill in angiographic procedures. Care needs to be taken to prevent guide wires
reaching the aortic arch during abdominal endovascular procedures for AAA, as there is a risk
of stroke, guide-wire dissection, or perforation by the tip of the guide wires. If the device is
measured incorrectly and is too short, an extension piece may be added, but if the device is too
long, it may not be possible to engage the contralateral limb or the distal ends may
inadvertently cover the internal iliac artery on one or both sides. In isolated cases we have
found it necessary to catheterize the contralateral limb from the left brachial artery so that
access from the femoral artery can be achieved. This requires capture and exchange of the
wire guide. In extreme cases using this technique it is possible to simultaneously push and pull
the limb extension into position.
When the neck is short and severely angulated, the correct device may require a custom-made
device. Occasionally the insertion of a stiff deployment sheath will alter the angulation of the
aneurysm sufficiently to produce a measurement mismatch and failure of the EVAR. Once
inserted and deployed it is almost impossible to remove an endograft by percutaneous access.
In such cases where conversion to open surgery is impossible and the aneurysm sac is large
enough, an alternative is to park the endograft in the aneurysm sac and perform a second
procedure with the correct-sized graft at a later date.
A Type I endoleak at the conclusion of an endograft placement requires immediate correction,
as the risk of rupture has not been reduced. Small calcific plaques may prevent complete
opening of an endograft, or the neck may be more angled than first thought. In most cases a
Type I endoleak may be corrected by further expansion using a large-volume, low-pressure
balloon, provided the endograft is of sufficient caliber. Where this fails it is sometimes possible
to use a very large-diameter balloon expanded stent with a high hoop strength inside the
endograft to cause more rigid expansion of the endograft and a better seal at the neck of the
aneurysm (Fig. 11-16).
If the internal iliac artery is to be covered by one of the limbs of the endograft, internal iliac
embolization is usually performed to prevent a later endoleak via a patent internal iliac artery. At
some centers, this is done as a separate procedure to reduce anaesthetic time and iodinated
contrast load. Large-diameter fibered occlusion coils should be placed as close to the origin of
the internal iliac artery as possible to reduce the risk of buttock claudication and to provide the
greatest opportunity for collateral arterial supply from the contralateral internal iliac artery. In
cases where both internal iliac arteries are occluded, external iliac-to-internal iliac artery
collaterals develop but buttock claudication is common.
Complex endograft procedures with significant manipulation of the device and the use of
multiple access catheters
have a high morbidity and sometimes a lethal rate of trash embolism. Suprarenal loose
atheromatous material is dangerous and should be noted if present on the planning CT scan.
Atheroemboli may occur after angiographic or surgical procedures and are a major cause of
morbidity and mortality (30). Impotence is a rare complication of endograft repair in males but
is a good reason to attempt to preserve both internal iliac arteries if possible.
FIGURE 11-16. Type I endoleak at deployment. Type I endoleaks at the upper end of the
endograft are usually large and obvious. If they are due to incomplete expansion of the
endograft, they are easily fixed but sometimes an additional extension endograft is
required. In this example the endograft was expanded by insertion of a very large Palmaz
(Cordis J&J, USA) stent. This is a good solution for endoleaks due to sharply angled
necks.
If the endograft is completely deployed but there is a small Type II endoleak, it is our practice
to perform a contrast-enhanced CT at 1 month postprocedure. In some cases the endoleak will
have closed, but if not, it can be treated by endovascular means.
MANAGEMENT OF ENDOLEAKS
The need for surveillance and management of endoleaks is the principal cost of endografts
compared to conventional open surgical repair. False aneurysms also occur at the graft
anastomosis site following conventional graft surgery but at a much lower rate than after EVAR
so that imaging surveillance is not generally performed. Not all endoleaks need intervention, as
aneurysm shrinkage can occur even in the presence of an endoleak. Such endoleaks are
usually small and Type II in nature.
An endoleak (Table 11-2) is defined as a communication from the arterial circulation to the
aneurysm sac. Endoleaks may occur from the time of deployment of the graft or develop at a
later date months or years following deployment. However, not all sac enlargement or failure of
shrinkage after treatment is due to endoleak and a condition of low-pressure hygroma or
seroma exists (31). Imaging is used extensively to identify the presence or absence of an
endoleak and to confirm the shrinkage of the aneurysm sac.
Imaging modalities used are color duplex ultrasound and CT (32). The CT protocol should allow
time for a small endoleak to fill with contrast and arterial and delayed imaging is required.
Angiography is usually indicated only when a leak has been identified by less invasive means or
when there is unexplained enlargement of the aneurysm sac. Type I endoleaks are usually large
and obvious.
Dilatation of the aneurysm neck and migration of the endograft distally or separation of the
endograft limbs from the body of the endograft produce a large Type I leak that may proceed
rapidly to rupture of the sac.
Type II leaks, on the other hand, are more subtle and harder to find. With color duplex
ultrasound the flow pattern in the endoleak may indicate that endoleaks will seal spontaneously
(33). Endoleaks that are effectively a channel from one vessel to another are less likely to close
than channels that are endconnections to the aneurysm sac. Angiography at the end of an
EVAR will often show extensive collaterals between lumbar vessels. In our experience a
persistent Type II endoleak always has flow from an inflow vessel to an outflow vessel or
vessels (Fig. 11-17). The exact site of the inflow may be difficult to find without angiography.
Carbon dioxide angiography is particularly sensitive for detecting a small Type II endoleak.
More recently it has been found that magnetic resonance angiography is 50% more sensitive
than CT angiography for detecting a small Type II endoleak (34). Unfortunately this technique
cannot be used for endografts containing stainless-steel stents, more because of the
susceptibility artifact than any real risk of displacement of the endograft.
Persistent Type II endoleaks result in pressurization of the sac and the contents remain liable to
thrombolysis and
variation in the size of the channel within the thrombus. Type II endoleaks can rupture if
untreated, and failure of shrinkage or enlargement of the aneurysm sac is worthy of further
investigation. Where there is no easy transluminal access through lumbar or inferior mesenteric
arteries, a direct translumbar approach is performed. It is then possible to catheterize the inlet
and outlet vessels selectively from the translumbar sheath (Fig. 11-18).
FIGURE 11-17. Type II endoleak with collateral filling. Generally a Type II endoleak is
associated with at least one inflow and a second outflow vessel. The aneurysm sac acts
as a collateral pathway between the inflow and the outflow. In this example, a Progreat
microcatheter (Terumo, Japan) has been used to catheterize the ascending lumbar artery
on the left side to reach the aneurysm sac. A: A contralateral lumbar artery and the median
sacral artery fill from the sac. B: All these arteries were occluded with 0.018 microcoils,
and a follow-up angiogram confirmed sealing of the endoleak.
Complete occlusion of the pathway is required, as a few coils in the aneurysm sac will not
promote permanent occlusion. In the presence of a significant endoleak the entire volume of the
aneurysm sac is potentially liquid. Contrast injected into the aneurysm sac is able to diffuse
widely, and at times attempts to catheterize an outlet vessel may be foiled by contrast diffusion
into the aneurysm sac thrombus. Our experience of thrombin injection into the aneurysm sac to
close an endoleak was unsatisfactory.
When the aneurysm sac does not decrease in size or even enlarges slightly and there is no
radiologic evidence of endoleak, a state of endotension is said to occur. In such cases where
the sac has been punctured, clear or serous fluid has been found. A similar finding has been
reported after open repair using PTFE material (35). In our personal series of more than 400
endograft repairs using Dacron-covered stents we have not found a definite case of
endotension. In one patient where no other cause was found for the slight but continued sac
enlargement, direct pressure measurements did not reveal elevated pressures within the
aneurysm sac or evidence of an endoleak. However, others (36) are convinced of the existence
of this condition and it may be related to the type of graft fabric used.
As an alternative to imaging surveillance, insertion of pressure sensors in the aneurysm sac has
been performed in humans (37). In one limited study these sensors have confirmed a decrease
in pressure within the sac following successful EVAR but the decrease in pressure has not been
immediate. In the first human study, the pressure sensors detected elevated pressure in the
presence of endoleaks. However, the presence of high pressure in one section of the aneurysm
sac may not always be reflected across the entire sac. An experimental model study showed
that the pressure was highest at the site of greatest expansion of the aneurysm sac (38).
Treatment of Type I endoleaks requires extension of the EVAR either by a sleeve endograft or
by use of a fenestrated endograft. We have used ONYX (Micro Therapeutics Inc., Irvine, CA),
(a nonadhesive liquid embolic agent comprised of an ethylene vinyl alcohol copolymer dissolved
in dimethyl sulfoxide and suspended micronized tantalum powder to provide contrast for
visualization under fluoroscopy) as our preferred occluding agent for Type II endoleaks. It is
delivered through a compatible microcatheter and is used to occlude the outflow vessel or
vessels, the path across the aneurysm sac, and then the inflow vessel (Fig. 11-19). Unlike coils,
ONYX prevents late recanalization of the occluded vessel. It is extremely opaque due to the
micronized tantalum powder it contains. Although it is possible to catheterize a Type I endoleak
and fill the endoleak space with a substance such as ONYX or occlusion coils, this has not
been a durable treatment in our hands.
FIGURE 11-18. Direct translumbar puncture for endoleaks. When the lumbar arteries
cannot be selectively catheterized, it is possible to puncture the aneurysm sac directly
using a sheath needle. It is then usually possible to catheterize the lumbar arteries through
the sheath. (See also Fig. 11-5.) A: The lumbar collateral is clearly seen but it proved
impassable. The direct injection angiogram (B) filled the outlet lumbar artery on the
opposite side, which was not visible on the normal angiogram.
FIGURE 11-19. ONYX for treatment of endoleaks. ONYX is a very useful substance for
occlusion of endoleaks, as it flows slowly and will not fix a microcatheter in place. A: In this
example ONYX has been used to seal a Type I endoleak (arrow). B: The ONYX has filled
a space much more extensive than the angiogram suggested. This is a common finding, as
often the contents of an aneurysm sac with an endoleak are semi-liquid.
LONG-TERM OUTCOME
Studies comparing open surgical repair to endograft repair of AAA show that both methods are
effective in preventing aneurysm rupture and that the late risk of rupture following endografting
is 1% per year. The 5-year survival after both is approximately 70% (39).
The aneurysm-related death rate appears to be lower following EVAR provided anatomy is
suitabledue to a lower perioperative mortality rate. The major limitation of EVAR remains the
need for ongoing surveillance and the increased incidence of intervention in the years following
a successful treatment. Studies of the devices used show fairly similar results for similar
devices (40, 41, 42, 43). Failed grafts are most often managed by further intervention with
success.
The results of the Eurostar registry (44) have caused a much better appreciation of the forces
affecting an endograft as the aneurysm thromboses and shrinks. Early devices produced an
excellent initial result but poor long-term protection due to endoleaks (45). In addition to the
forces exerted by the blood flow on the endograft, the shrinkage of the sac after endografting
causes quite marked torsion force on the endograft. This appears to be the cause for some
limb separations seen in the Eurostar Registry and the lessons learned have influenced
endograft design.
Following device deployment in short-necked aneurysms, we have observed late device failure
with detachment of the uncovered suprarenal fixation from the covered trunk of the endograft.
There is no room for complacency in late follow-up of endografts, as the Eurostar data show a
higher failure rate 4 years after placement.
The evolution occurring with graft design has made them more durable and useful with each
step forward. One unsolved question is when to cease follow-up. As all these patients are
predisposed to developing other aneurysms, follow-up of all EVAR patients is required on a 2-
to 5-year basis. The authors have many patients now being followed every 3 to 5 years, as
complete shrinkage of the aneurysm has occurred. One patient has the metallic stent skeleton
of the endograft totally fragmented and collected inferiorly in the graft with the aneurysm sac
still completely absorbed. A contrast-enhanced CT shows that the aortic diameter is that of the
original device.
EVAR is now an established procedure in the treatment of AAA. As devices continue to evolve
and improve, the percentage of patients suitable for this minimally invasive technique will
continue to increase. The use of magnetic resonance for follow-up may reduce the radiation
burden for patients but will not reduce the cost to society of current follow-up programs.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 12 - Endovascular Therapy
of Aortic Occlusive Disease
Chapter 12
Endovascular Therapy of Aortic Occlusive Disease
Renan Uflacker
AORTIC OCCLUSIVE DISEASE

Aortic occlusive disease (AOD) occurs commonly in association with peripheral arterial disease
(PAD), but focal isolated infrarenal aortic stenosis not extending to the bifurcation or iliac
arteries is less frequent (1). Significant lesions in the aortoiliac arterial segment are detected
easily by palpation of the femoral pulses. Any diminution of the palpable femoral pulse may
indicate that a more proximal obstruction exists. Obstructive lesions may be present in the
infrarenal aorta, common iliac, internal iliac (hypogastric artery), external iliac artery, or
combinations of any or all of these vessels. On the other hand, degenerative nonstenotic
atheromatous disease existing in the aorta and/or iliac arteries and may manifest itself by
atheroembolism to the foot, namely, the blue toe or trash foot syndrome. Distal embolic
events results in focal painful areas of bluish discoloration of the toes, and the patients may
report multiple episodes of these painful symptoms, involving one or both feet, preceding the
major peripheral ischemic event (Fig. 12-1).
Total occlusion of the aorta is usually progressive, starting with a focal stenosis gradually
obliterating the whole lumen of the infrarenal aorta (Fig. 12-2). Acute thrombosis may develop,
with sudden worsening of the symptoms. Clot propagation will define the severity of the
occlusion (Fig. 12-3). Surgical bypass grafts have traditionally been used to treat
atherosclerotic occlusive disease of the infrarenal aorta and its bifurcation, in patients with
lifestyle-limiting claudication or limb-threatening ischemia. The surgical management of the
totally occluded abdominal aorta is a highly complex procedure and complications are more
likely to be seen. Despite the good immediate outcomes and long-term patency rates of 90% to
95% at 5 years, the surgical repair of AOD has been associated with a 3.3% to 4.6%
perioperative mortality and 8.3% to 13.1% major early complication rate, including erectile
dysfunction, ureteral damage, intestinal ischemia, spinal cord injury, and acute occlusion (2,3).
Up to 26.5% of patients may need a second intervention during the followup period (4), and
while the 10-year survival rate may be as high as 92.9% for anatomical bypass, the 10-year
survival for extra-anatomical bypass may be only 29.5% as described in the literature (5).
Patients with infrarenal AOD are typically younger (<60 years) than other patients with
peripheral vascular occlusive disease. They are usually cigarette smokers and have a lower
incidence of hypertension and diabetes, however, they present a higher incidence of serum lipid
abnormalities. The incidence of AOD is about the same for males and females and there is a
high incidence of aortic hypoplasia, particularly in females.
Patterns of Aorto-iliac Occlusive Disease

Aorto-iliac atherosclerotic occlusive disease occurs in several levels and manifests with distinct
clinical symptoms and signs. The majority of patients with leg ischemia due to aorto-iliac
atherosclerosis also presents with multilevel arterial occlusive lesions with involvement of the
infra-inguinal arteries (Type III), and in only one third of patients, the occlusive process is limited
to the supra-inguinal ligament vessels (Type II) (Fig. 12-4). Focal disease of the aorta and
bifurcation is less common, and only about 10% of patients fall within this pattern (Type I) (Fig.
12-5, Table 12-1).
The juxtarenal segment of the aorta is usually preserved from severe atherosclerotic
involvement, even in instances of infrarenal aortic total occlusion, and the infrarenal aorta is
usually occluded by retrograde thrombosis only. The posterior wall of the infrarenal aorta is
always more compromised by atherosclerotic plaques, which may jeopardize collateral
circulation through the lumbar and median sacral arteries (Fig. 12-6).
Patients with Type I disease, compared with the cohort with multisegment disease (Type III),
have a lower incidence of hypertension and diabetes mellitus, but serum lipid abnormalities,
such as cholesterol and triglycerides, are elevated and high-density lipoprotein levels are low.
There is not a male-to-female discrepancy as in the Type III group, and epidemiologically,
affected women have commonly experienced premature menopause secondary to
hysterectomy or radiation therapy and loss of the protective effect of estrogen against the
development of atherosclerosis. Hypoplasia of the aorto-iliac segment has also been described
as a predisposing factor. A suprarenal aorta diameter of 19 and infrarenal aorta diameter of
13 mm is judged consistent with hypoplasia. Using these criteria, approximately one quarter
of women who are candidates for revascularization demonstrate hypoplasia of the aorto-iliac
segment. The etiology of this entity may involve overfusion of the fetal double aortas, as there
is a single large distal lumbar artery in many of these patients, instead of the normal paired
arteries (6).
Patients with Type III, or combined aorto-iliac and infrainguinal, occlusive disease are usually
older by a decade, have a higher incidence of diabetes, hypertension, and associated cardiac
and cerebrovascular disease, and are predominantly males (6:1). This cohort of patients has
predominant limb ischemia with claudication at <50 m.
The Female Problem

A unique clinical presentation of AOD is the small aorta syndrome, or focal atherosclerotic
stenosis of the lower abdominal aorta. AOD in women is a difficult problem to manage,
because the aorta is small, and the atherosclerosis is, in general, focal and limited to the distal
aorta, rarely reaching the iliacs (Fig. 12-7). The patients are usually younger, 40 to 50 years of
age, short in stature, and in general have an abnormal lipid profile and are heavy tobacco users
(7). The external iliac arteries and the superficial femoral arteries are usually spared. The
younger age of the female patients and the presence of atypical symptoms for the patient
profile often delay the diagnosis, at times with severe consequences. Due to the size of the
vessels involved in the female patients, surgical as well as endovascular repair is challenging.
Aorto-bi-iliac graft placement has been the treatment of choice in these cases, but more
recently, the endovascular approach has been increasingly used and angioplasty may be an
option for treatment. The small size of the aorta (13 mm) and iliac arteries may preclude
stenting of the distal aorta above the bifurcation, in favor of kissing stenting of the iliac arteries
extending into the aorta side by side, moving toward the aortic bifurcation. Due to the small size
of the iliac arteries, risks of intimal hyperplasia and stent occlusion are slightly higher than with
single aortic stenting. One additional risk of balloon angioplasty or stenting is the discrepancy in
size between the distal aorta and the small common iliac arteries, since oversizing the balloon
may cause iliac artery rupture.
FIGURE 12-1. A: Aortogram of a patient with degenerated nonstenotic atheromatous

disease in the infrarenal aorta manifested by atheroembolism to the foot, causing blue
toe or trash foot syndrome, showing diffuse atherosclerotic ulcerated disease of the
aorta. B: Aortogram after placement of an Endotexcovered stent deployed in a tubular
manner within the infrarenal aorta, covering the atheromatous disease. There was
resolution of blue toe syndrome and no further events of atheroembolism occurred.
FIGURE 12-2. A 69-year-old man presented with bilateral claudication. Femoral pulses
were palpable but diminished. A: Aortogram showed a tight stenosis of the infrarenal
aorta, ~1.5 cm below the renal arteries. The lesion was posterior and eccentric. B: Balloon
angioplasty with a 12-mm balloon was followed by placement of a 14-mm Wallstent,
further dilated with a balloon.
FIGURE 12-3. A 60-year-old man with a history of peripheral vascular disease, developed
acute occlusion of the abdominal aorta with severe ischemia of both legs. A: Aortogram
performed through the left brachial artery. Note the total occlusion of the infrarenal aorta.
B: The catheter was advanced into the occlusion and 250,000 IU of urokinase (UK) was
injected in a pulse-spray fashion, followed by additional infusion of the same dose over 1
hr. Note the partial recanalization of the aorta. C: At 16 hours of infusion there is
improvement of the aortic recanalization, but the iliac arteries are not visible yet. D:
Infusion was continued for 10 more hours and the aorta is patent. E, F: Balloon angioplasty
and additional infusion promoted recanalization of the left iliac. G, H: Final aortogram
following an additional 16 hours of infusion into the aorta showed patent aorta and iliac
arteries, with a total of 43 hours of treatment and the use of 10,750,000 IU of UK.
FIGURE 12-4. An 80-year-old man presented with bilateral lower extremity claudication
and reduced femoral pulses. A: Abdominal aortogram performed from the left showed a
large filling defect within the lumen of the infrarenal aorta. The common iliac arteries also
present verrucoid atheromatous plaques causing obstruction. B: Aortogram after balloon
angioplasty and placement of Palmaz stents in the aorta and iliac arteries. Note the
adequate patency of the aorta and iliac arteries but with bulging of the walls of the vessels.
FIGURE 12-5. A 69-year-old man presented with bilateral buttock and thigh claudication
with reduced femoral pulses. A: Aortogram, in oblique view, showed an eccentric
posterolateral plaque in the distal abdominal aorta with >90% stenosis. Balloon angioplasty
was initially performed with kissing balloons, followed by single 14- and 16-mm balloons. A
20 40-mm Wallstent was placed and dilated with a 16-mm balloon. B: Final aortogram
showed no residual stenosis and no pressure gradient across the stented lesion.
TABLE 12-1 PATTERNS OF AORTO-ILIAC OCCLUSIVE DISEASE
Disease Pattern
Above the inguinal

ligament (30%)
Type I (10%) Distal aorta and common iliac
Type II (20%) Distal aorta, common iliac, external iliac, common femoral
Multisegment
disease (70%)
Segmental involvement of aorta and iliac system combined with

Type III
superficial femoral and/or tibial disease
FIGURE 12-6. A 56-year-old man with bilateral lower limb claudication due to aortic
occlusion near the bifurcation. A: CT of the abdominal aorta, showing the prominent
intraluminal plaque, with a small opening with the inferior mesenteric artery (IMA) visible.
B: Aortogram showing the focal occlusion of the distal aorta with development of the
collateral circulation. Note the prominent IMA. C: Lateral view of the aortogram showing
the posterior location of the large calcified atheromatous plaque causing severe stenosis
with a small aortic lumen. D: Kissing balloons dilating the aorta. E, F: Postangioplasty
aortogram in frontal and lateral views showing the patent aorta. Note that the IMA is not
filling. There was obstruction of the left iliac artery, which was treated by surgical
thrombectomy.
Leriche's Syndrome
Leriche's syndrome is a vascular disturbance usually affecting young males caused by
atheromatous involvement or occlusion of the abdominal aorta by a thrombus just above the site
of its bifurcation, but usually extending to both common iliac arteries. A triad of symptoms,
consisting of absent or diminished femoral pulses, buttock claudication, and penile erectile
dysfunction, characterizes the syndrome. Other symptoms are leg claudication, pain, fatigue in
the lower limbs, cramps in the calf area, ischemic pain in the feet, pallor, and coldness of the
feet and legs. Onset is usually at between 30 and 40 years of age. The aortic occlusion in most
cases presents after gradual progression of symptoms, and large intercostal, lumbar, and
epigastric collaterals proximally reconstitute internal and external iliac, femoral, and distal
circulation. If the onset of the occlusive disease is acute, the ischemic symptoms may be more
severe and may include rest pain or tissue loss. The syndrome is strongly related to tobacco
use in younger subjects.
The syndrome was first described in 1814 by Robert Graham (1786-1845) (8). Leriche first
operated for this syndrome on a 29-year-old truck driver who for 2 years had been suffering
from intermittent claudication with severe cramps in the leg musculature after a few hundred
meters of walking and cramp pains at night. In the last weeks before the operation he
complained of not being able to complete intercourse, as both erection and ejaculation were
disturbed. Following surgery, the patient was fully capable of walking and had fathered a son
(9). In autopsy studies, Leriche observed that patients with terminal aortic thrombo-obliteration
have a short infrarenal aorta, and a high iliac bifurcation with an acute takeoff angle, compared
with the normal population. His postulate that this was responsible for creation of turbulent flow
and propensity for atherogenesis (10) was later confirmed by other authors (6). At Leriche's
time the treatment was largely confined to sympathectomy and limb amputation.
FIGURE 12-7. A 43-year-old female, heavy smoker, with bilateral claudication and
hypoplastic aorta. A: Aortogram shows a focal stenosis in the distal infrarenal aorta. B, C:
Oblique and lateral views of the aortogram show the stenosis to be predominantly
posterior and almost weblike. Note the enlargement of the inferior mesenteric artery.
Single-balloon angioplasty was performed with a 10-mm balloon. D: Post angioplasty
aortogram showing the patent aorta.
Aortic Embolism
Acute occlusion of the aortic-iliac segment by saddle embolism at bifurcation of the aorta is not
as common as atherosclerotic aortic occlusion, but the hemodynamic effects may be similar to
those of acute thrombosis (11) (Fig. 12-8). However, collateral circulation may be poorly
developed and the ischemia is more acute. Abrupt occlusion of the aortic bifurcation from
embolism is characterized by the sudden onset of pain, pallor, paralysis, and coldness in the
legs (12). The location of the embolism also determines the degree of ischemia. Propagation of
the thrombus, cranially or caudally, also influences the degree of ischemia by compromising the
takeoff and reentry sites of the collaterals. The vessels above and below may be relatively
normal and removal of the thrombus by surgical thrombectomy or transfemoral embolectomy
usually resolves the problem without much sequelae. More recently, several techniques of
mechanical thrombectomy have been developed and used to
threat thrombosis of the abdominal aorta and iliac arteries (13), usually requiring the
association of thrombolytic therapy. The heart is the main source for saddle aortic and
peripheral embolism, however, the presence of thrombi in the atherosclerotic and/or
aneurysmal aorta with peripheral arterial embolism is also a common scenario (14). Large
thrombus formation in a morphologically normal aorta is a rare event, but large thrombus may
form from ulcerated aortic plaques. Since most saddle emboli arise from the heart, preventive
therapy is important and cardiac condition favoring embolism should be appreciated and
treated.
FIGURE 12-8. Aortogram in a patient with atrial fibrillation and massive embolism in the
distal aorta. Note the saddle embolus in the distal aorta, with development of some
collateral circulation through the lumbar arteries, despite this being an acute event.
Coarctation of the Aorta and/or Midaortic Syndrome

Coarctation of the aorta is a congenital obstruction of vessel produced by an internal diaphragm
or ridge of tissue composed of intima and media, more commonly encountered in the thoracic
aorta, just past the ligamentum arteriosum. Coarctation of the abdominal aorta has been
termed hypoplasia of the abdominal aorta, midaortic dysplasia, midaortic syndrome (MAS),
atrophy of aorta, atresia of the terminal aorta, and atypical coarctation (15). The pathogenesis
is still controversial. Hypertension is an almost-universal feature of this disorder. In general it is
detected in early adulthood, with lower extremity claudication and hypertension if the lesion is
above or at the level of the renal arteries. MAS is a clinical condition generated by segmental
narrowing of the abdominal or distal descending thoracic aorta. It may be caused by Takayasu
or temporal arteritis (giant cell arteritides), neurofibromatosis, fibromuscular dysplasia,
retroperitoneal fibrosis, mucopolysaccharidosis, and Williams syndrome. MAS may also be
congenital, ascribed to a developmental anomaly in the fusion and maturation of the paired
embryonic dorsal aortas. Segmental aortic stenosis may be located at the suprarenal,
interrenal, or infrarenal aorta, with a high propensity for concomitant stenoses in both the renal
(63%) and the visceral (33%) arteries. In one series the most common location of the aortic
narrowing was interrenal (52%) (Fig. 12-9), and the remaining cases were confined to the
suprarenal, infrarenal, and entire abdominal aorta diffusely in 11%, 25%, and 12% of 119
patients, respectively (16).
Hypertension proximal to the aortic stenosis and relative hypotension distal to it are
characteristic findings in MAS. Typical manifestations include headache, early fatigue on
exertion, and bilateral lower limb claudication. The severity of hypertension is the primary
indication for intervention and the factor determining procedural timing. As a great proportion of
patients with MAS is children or teenagers, the clinical benefits of early surgical intervention to
reverse refractory hypertension have to be weighed against the repercussions pertaining to the
insult of surgery on the developing aorta. Open surgery is the primary treatment of tubular
aortic narrowing, MAS, associated with renovascular hypertension and visceral artery stenosis
or occlusion (Fig. 12-9). This entails aortoaortic bypass of the diseased segment or, less often,
patch aortoplasty and usually bypass grafting of the stenosed renal and visceral arteries
performed with autologous conduits, particularly in the youngest patients (17). Multisaccular
aneurysm developing in association with abdominal aortic coarctation is a rare occurrence but
may cover the diagnosis of tubular aortic stenosis and may require surgical reconstruction (18).
Endovascular therapy may provide a sound minimally invasive treatment for MAS caused by
discrete aortic stenoses that do not encompass the mesenteric and renal arteries (19).
Proximal hypertension is improved or cured in >70% of patients. The prognosis after
uncompromised surgical reconstruction is rewarding in the mid- and long term in patients with
congenital aortic coarctation but deteriorates in patients with aortoarteritis and recurrent
inflammatory activity.
Aortic Arteritis
Takayasu arteritis (TA) is a nonspecific granulomatous inflammatory arteriopathy of unknown
cause that results in occlusion or, less commonly, aneurysmal degeneration of large and
medium-sized elastic arteries. TA involves the thoracic and abdominal aorta and their large
branch arteries, and is considered an independent entity. The disease was first described in
1908 by Takayasu (20), an ophthalmologist, in a young female patient with retinal
neovascularization and absent radial pulse. Subsequent descriptions of the disease have
emphasized the pulseless syndrome, with involvement of the brachiocephalic arteries. Its
incidence is low, being reported in 1 in 3,000 autopsies in Japan and as few as 2.6 cases per 1
million in the United States (21,22). The female-to-male ratio was reported to be 8-10:1 (23).
The clinical features depend on the organ involved. The patients present with claudication if the
lower abdominal aorta is involved, hypertension if the renal arteries are involved, stroke if the
cerebral vascular vessels are involved, or angina and myocardial infarction symptoms if the
coronary arteries are involved. Arteriography is the best modality for the diagnosis of TA,
together with magnetic resonance angiography and computed tomography (CT) angiography
(24,25). The disease does not just affect the arterial bifurcations but usually involves the entire
length of arteries. The disease has a very
peculiar distribution within the subclavian, axillary, carotid, and renal arteries and infra-
abdominal aorta. The clinical presentation of TA is not the same as that of atherosclerosis.
Patients with atherosclerosis are usually elderly while patients with TA are young, but despite
their youth, they still may have severe cardiac, renal, and pulmonary problems. Therefore,
these patients should undergo extensive medical evaluation prior to surgery. It is preferable to
avoid surgery during the acute phase of the illness. The surgical procedure consists of a
bypass operation to vessels normal on angiography proximal and distal to the occlusive or
stenotic lesion. Sometimes surgical bypass may be associated with aortic branch stenting if
necessary, particularly in the renal arteries (Fig. 12-9). Endovascular treatment was reported in
a series of 16 patients with symptoms of hypertension or severe bilateral lower limb
claudication (26). Aortography revealed stenotic lesions in the descending thoracic aorta in 5, in
the abdominal aorta in 10, and in both vessels in 1 patient. Involvement of arch vessels was
identified in four patients, and of the renal artery in four patients. Double-balloon angioplasty
was performed in eight patients. The initial technical and clinical success was 100%. The
maximum follow-up period was 52 months (mean, 21 months 2 weeks). Ankle-brachial index as
determined by Doppler ultrasound improved considerably in 10 patients. Three patients had
symptoms of restenosis during follow-up. Cumulative patency rate by life-table analysis was
67%, showing that percutaneous transluminal angioplasty has a definite role in the management
of TA compared to surgical revascularization procedures (26).
FIGURE 12-9. A: A young patient with Takayasu arteritis with stenosis of the middle aorta,
with occlusion of the left renal artery, and stenosis of the right renal artery. B: Postsurgery
CT angiogram of the abdominal aorta showing a large-caliber aorto-aortic bypass across
the stenosis. The right renal artery was treated with a stent. Note the persistence of the
large inferior mesenteric artery.
Aortic Dissection
Dissections are usually associated with atherosclerotic disease; the diseased intima acts as the
substrate for the dissection. Other diseases, such as fibromuscular dysplasia and cystic medial
necrosis, may predispose to dissection. An important contributor and risk factor is systemic
hypertension. Isolated dissection of the abdominal aorta or iliac arteries is rare (16,27).
Dissection involving the abdominal aorta is more commonly the result of the abdominal
extension of a Type III thoracic aortic dissection (Fig. 12-10). Dissections can be iatrogenic,
traumatic, or spontaneous. Spontaneous dissection of the aorta occurs as a result of structural
defect in or degeneration of the aortic media, which allows blood to gain entry to the media and
dissect the aortic wall. Bleeding from the vasa vasorum into the media is suspected to be an
initiating event, particularly related to systemic hypertension. Dissection may also start with an
intimal tear or a penetrating atheromatous ulcer followed by intimal dissection, creating a cavity
parallel to the true lumen of the aorta and distorting the lumen of the aorta. An intramural
hematoma may also develop from penetrating ulcers, becoming circumferential but not
necessarily distorting the true lumen. The ulcers occur most commonly within the descending
thoracic aorta in elderly hypertensive men, and may extend to the abdominal aorta.
The aortic dissections are currently easily depicted with spiral CT technology and a linear
radiolucent flap is observed within the lumen of the aorta, separating the lumen into two
compartments filled with contrast material. Dilation of the overall diameter of the aorta may be
significant, and in some cases the false lumen appears larger than the distorted and
compressed true lumen (Fig. 12-10). Evaluation of the inflow and outflow should be performed
to guide therapeutic decision making. Angiography is important to locate the inflow and outflow
of the dissection. Aortography also plays an important role in association with the CT scan to
identify the compromised branches of the aorta and to locate their connection to the true or
false lumen.
FIGURE 12-10. A 70-year-old patient with Type B dissection extending into the abdominal
aorta. A: Aortogram showing that the false lumen is larger than the true lumen in the
descending aorta. B: Distal abdominal aorta showing the small true lumen with the right
renal artery and the superior mesenteric artery (SMA) connected. C: Higher up in the aorta
the false lumen is small. D: Access from both sides was obtained, a larger sheath was
placed in the right side, and an intravascular ultrasound (IVUS) probe was placed from the
contralateral side. E: Image of the IVUS showing the two lumens and the TIPS set needle
pointing against the flap. F: Puncture of the flap was made and a guide wire and catheter
were advanced to the other lumen. G: Balloon dilation with a 12-mm balloon. H: CT
demonstrates equal opacification of the two lumens and communication of the true lumen
with the SMA. I: CT angiogram at the level of the fenestration created by the balloon. J:
Right renal artery, with the stent connected with the true lumen.
One of the main complications of aortic dissection at the level of the abdominal aorta is total
occlusion of the aorta and iliac arteries or occlusion or significant restriction of blood flow into
the visceral arteries, such as the celiac artery, superior mesenteric artery (SMA), and renal
arteries. The occlusion or stenosis of the celiac artery and/or SMA may lead to mesenteric
ischemia, and occlusion or stenosis of one or two renal arteries may cause hypertension or
renal insufficiency. In several instances there is rupture of continuity of the aortic intima entering
one of the renal arteries, and sustained acute hypertension may develop. The ostium of the
renal artery may be connected to the false lumen or be partially occluded by an intimal flap.
Treatment of abdominal aortic dissection is by no means well established, and multiple
interventions may be used together, dictated by the extension of the disease or location of the
inflow and outflow. Endovascular treatment with stent-grafts and bare stent combination can be
used in many cases, preserving the ostia of the main aortic branches and enlarging the true
lumen while partially collapsing the false lumen to cause thrombosis. Frequently, the branches
of the aorta need to be stented to reestablish the connection with the main lumen of the aorta
(29). This is particularly important for reperfusing of the kidneys and other viscera. In such
cases, catheterization needs to be performed from the true lumen to reach the branch
connected to the false lumen. In the event of an intimal flap causing occlusion of the renal
artery, the only chance of saving the renal function of the compromised kidney is stenting the
artery. Stenting of abdominal aortic branches may require fenestration of the dissection flap
(Fig. 12-10).
Fenestration of an aortic dissection is a heroic procedure designed to rapidly restore the
communication between the true an the false lumen of the aorta. Conventional technique for
fenestration includes transfemoral catheterization of the true or false lumen followed by the
creation of a communication across the intimal flap separating the two lumens. Puncture of the
flap is performed with a needle used for the TIPS procedure, under fluoroscopic and
intravascular ultrasound guidance. Once the perforation is done, a guide wire is advanced from
one to the other lumen and the orifice is dilated with a large balloon over the wire. More than
one fenestration can and should be created (29). An alternative technique is the tearing of the
intraluminal flap using a guide wire and a snare loop. Using the same technique described
above, the guide wire is captured within the other lumen with the snare loop, and the ensemble
is pulled down to rip the membrane in the middle, thereby re-establishing communication
between the two lumens. Occasionally the flap may fail to tear apart in the middle and the
whole tissue may collapse into the abdominal aorta. In such cases, careful recanalization of the
lumen of the aorta and branches needs to be performed with aorto-iliac stents and, if
necessary, reopening of the aortic branches (Fig. 12-11).
It is difficult to give a good account of outcomes of fenestration to treat dissection, because
there are no large published prospective studies; a variety of techniques and indications
characterizes the approximately 117 cases reported to date. Even the largest study reported
on only 40 patients (30), and there is a paucity of long-term follow-up data. Overall technical
success in revascularization exceeds 90% (31, 32, 33). Visceral artery involvement is predictive
of a poor outcome and proves fatal in up to one third of patients due to the extent of vascular
involvement and the development of multiorgan failure (31). There is little consensus regarding
the frequency with which fenestration is required or whether stent placement alone is adequate.
It seems to be agreed that fenestration alone is inadequate and that stent placement is
required to address any fixed or dynamic obstruction (34). Rupture of the dissected aorta,
although a real risk, seems to be an uncommon procedural complication, but there is still
potential for extension of the dissection in spite of fenestration (35). There has been no
prospective study comparing percutaneous with surgical fenestration. The results of surgical
fenestration seem to be worse, with an operative mortality rate of 43% for patients who
undergo emergency surgical fenestration (33). The role of fenestration in the era of stent-graft
placement is also unclear. Restoring normal pressure to the false lumen may be beneficial, and
restoring branch vessel patency may be easier after fenestration (34). There may be a role for
both approaches, with stent-graft placement being used to obliterate the false lumen after
decompression and, in suitable cases, to cover the tear leading to the false lumen (36).
FIGURE 12-11. A patient with dissection of the descending thoracic aorta and abdominal
aorta, with occlusion of the flow to the renal artery and the lower extremities. A: CT
angiogram of the abdominal aorta showing the two lumens in axial view. B: Coronal
reconstruction of the thoracoabdominal aorta showing the dissection extending into the
abdominal aorta. C: Aortogram showing the occlusion of the true lumen of the abdominal
aorta and right renal artery. D: Aortogram in the false lumen showing the occluded right
renal artery. E: The iliac arteries are patent, filling from the false lumen. F, G, H: A guide
wire was advanced into the false lumen, and a loop snare into the true lumen. After
puncture of the flap, the wire was passed through the fenestration and captured by the
loop snare. The wire and the snare loop were pulled together to rip the aortic flap in the
center. I: Unfortunately the whole intimal flap collapsed within the lumen, completely
occluding the infrarenal aorta. J: The iliac arteries are occluded proximally. K: Using the
bilateral femoral access balloon angioplasty and four Wallstents, two on each side, a
connection was created between the iliac arteries and the aorta at the level just below the
renal arteries. L: Final aortogram showed recanalization of the infrarenal aorta, with
patency of the renal arteries and iliac arteries. Only a lower pole right renal artery was
lost. M, N: Follow-up CT angiogram of the aorta showed patency of the aortic branches
and no residual flap within the aortic lumen.

Acute Occlusion of Aorto-iliac Bypass Graft and Stent-Grafts

Aorto-iliac bypasses for the treatment of aorto-iliac occlusive disease may fail after some time,
despite the excellent results in most patients. Graft failure may result from a variety of
etiologies and requires a combination of skills and experience for management. Surveillance is
important for long-term management of grafts, since revision of a failing graft results in higher
patency rates than thrombectomy of an occluded graft (37). Unexpected failure with acute
occlusion usually causes acute symptoms and often limb-threatening ischemia, requiring urgent
intervention. Symptoms may range from mild claudication, coolness, or pain to limb-threatening
ischemia with rapid tissue loss.
FIGURE 12-12. A 66-year-old man with a history of coronary disease developed rest pain
in the left and severe lumbar pain. There was occlusion of the 4-year-old aortofemoral
graft, with previous occlusion of a femoral-femoral graft that was never functional. Both
legs were pulseless. A: Initial aortogram performed by axillary approach with a 4-Fr
catheter showed total occlusion of the infrarenal aorta extending into the left femoral
artery. B: Pelvic arteriogram shows faint filling of the internal iliac arteries and
reconstitution of the common femoral arteries. C: The catheter was wedged into the clot,
which showed total occlusion during a test injection. rt-PA infusion was started at 5
mg/hour for 17 hours, to a total of 85 mg, with progressive advancement of the catheter.
After the 17-hour infusion, the aorta and the graft are patent. D: The left limb of the graft is
patent but shows a tight stenosis at the anastomosis of the graft with the left common
femoral artery. Femoral balloon angioplasty was performed with a 7-mm device. E: After
angioplasty, normal flow to the left leg was achieved as demonstrated. Thirtymonth follow-
up shows the patient to be asymptomatic.
The etiology of graft occlusion varies with the time interval from operation to the thrombotic
event. Occlusions within the first 30 days of surgery are attributable to the operative technique
(kinking, twisting, clamp injury, anastomotic problems, and intimal flaps), leading to low-flow
status. Grafts that fail from 30 days to 2 years after surgery do so as a result of neointimal
hyperplastic lesions, as a response to injury. Failure of a graft beyond 2 years is usually due to
the progression of distal atherosclerotic disease, which limits outflow of the limb and ultimately
leads to graft occlusion (Fig. 12-12). The vein
grafts may have a more gradual progression to failure, usually by vein valve fibrosis and wall
thickening, and the symptoms of ischemia may be less abrupt, due to the development of
collateral circulation (38).
Aortofemoral grafts used to treat aorto-iliac occlusion or stenosis may be affected by

reocclusion in up to 15% to 30% of patients within a period of 10 years after surgery, with 18%
to 28% occurring with acute thrombosis (38). In a review of 134 aortic occlusions in 123
patients, there were 10 patients who suffered recurrent aortic occlusions (RAOs). These
patients developed RAO after revascularization for primary aortic occlusion and presented with
signs and symptoms of acute lower extremity ischemia. The recurrent occlusions occurred in
one native aorta and in 10 aortobifemoral grafts. The etiology of the primary aortic occlusion
included chronic aortic occlusion in eight patients and acute aortic occlusion and aortic graft
occlusion in one patient each. Original primary operations performed included aorto-iliac
thromboendarterectomy with Dacron patch aortoplasty (one patient), aortofemoral bypass
(AFB; eight patients), and aortofemoral graft thrombectomy (one patient). All of the grafts had
end-to-end proximal anastomoses, and the diameter ranged from 12 to 16 mm. Secondary
operations performed for RAO included six axillofemoral bypasses, four redo aortobifemoral
bypasses, and one graft thrombectomy. All patients were managed with immediate
anticoagulation, expeditious arteriography, and revascularization. There were no perioperative
deaths, and no limbs were lost. Extra-anatomic bypass has proved durable. Redo
aortobifemoral bypass is useful in selected patients with surgically correctable lesions. The
cause of failure is usually in the distal anastomoses and related to fibrointimal hyperplasia.
Infection is a less frequent cause of failure (1% to 2% of cases), but with much more serious
consequences related to higher morbidity and mortality (39).
Aorto-iliac surgical grafts, as mentioned above, fail because there are many technical issues in
the early phase, and intimal hyperplasia and progression of the atherosclerotic disease in the
late phase. Whatever technique is used to declot the graft has to be backed up by the
treatment of the occlusive lesion that caused the thrombosis in the first place. Therefore,
mechanical thrombectomy, usually associated with thrombolytic therapy, has to be followed by
balloon angioplasty and, very frequently, by stenting (40). Streptokinase and urokinase were
originally described as the thrombolytics of choice to revascularize thrombosed aorto-iliac
grafts (40,41), but more recently rt-PA and Retavase have been more widely used for
revascularization of occluded surgical grafts in the distal aorta (Figs. 12-12 and 12-13).
FIGURE 12-13. A 58-year-old man with a history of diffuse vasculopathy with Leriche
syndrome, treated by aorto-bi-iliac bypass several years before, developed intense rest
pain in both extremities from acute thrombosis of the aorta and the graft to the iliac
arteries. A: Aortogram performed through the left brachial artery showed occlusion of the
aorta below the level of the renal arteries. Note the significant development of collaterals,
suggesting previous stenosis. B: Pelvic arteriogram showed reconstitution of both the
internal iliac arteries, the left common femoral artery, and the profunda artery. C: A
catheter with side holes was advanced into the left limb of the graft, which was totally
occluded. A bolus of 250,000 IU of urokinase was pulse-sprayed into the clot, followed by
an infusion of 250,000 IU/hour for 4 hours, reduced to 125,000 IU/hour for 12 hours. D:
Follow-up angiogram, 16 hours after the infusion, showed patency of the aorta and left
limb of the graft. E: A more distal angiogram showed patency of the external iliac artery
and superior femoral artery. A femoral-femoral bypass was created.
In a recent publication, 72 patients with aorto-iliac occlusive disease received daily intravenous
infusions of ultrahigh doses of urokinase either until reperfusion or untilafter at least three
cyclesno progress in recanalization could be documented on 2 consecutive days by duplex
scanning (42). Systemic lytic therapy was partially successful in 44 patients (61.1%).
Concomitant percutaneous transluminal angioplasty was performed in 41 patients (56.9%),
surgery in 7 patients (9.7%), and both in a further 5 patients (6.9%). In patients without
surgery, hemodynamic success was achieved in 39 patients (54.2%), and clinical success in 51
patients (70.8%). Compared to baseline results patients improved significantly in ankle/brachial
pressure index and in Fontaine stages (p < 0.001); the same results were seen after a mean
followup period of 62 months. Thrombolysis was complicated in four patients (5.6%) by
peripheral embolizations but no major bleedings or deaths occurred. Primary patency was 76%,
64%, and 43% after 1, 5, and 10 years, respectively. Male gender and distal location were
significantly correlated with lower primary clinical patency. In this particular publication, lytic
therapy appeared to be an alternative to surgical intervention in acute and subacute aorto-iliac
occlusive disease, with positive long-term results and a low rate of complications. However, the
literature is scarce, and so far there is little support and no level 1 evidence for the use of
endovascular techniques for salvage of aorto-iliac surgical grafts.
In the last 14 years there has been a significant shift in the paradigm for treatment of abdominal
aortic aneurysms and aortic-iliac occlusions with the use of stent-graft devices. Limbs of stent-
grafts may occlude in 3% to 4% of the cases (41) and may be treated by a combination of
procedures including mechanical thrombectomy, angioplasty with or without stenting, and
thrombolysis, and obviously, by bypass procedures (femoral-femoral bypass, axillofemoral
bypass, and AFB) (41, 42, 43, 44, 45). There is much more experience reported in the
literature on the use of endovascular procedures for salvage of aorto-iliac endografts than
surgical aorto-iliac grafts.
ENDOVASCULAR TREATMENT OF AORTO-ILIAC OCCLUSIVE

DISEASE
Preprocedure Assessment
Laboratory Studies
Laboratory studies are as follows.
A serum lipid profile that includes total cholesterol, low-density lipoprotein cholesterol, and
high-density lipoprotein cholesterol should be obtained.
If a history of diabetes exists, the glycosylated hemoglobin level (Hgb A1c) should be
checked. Excellent control of diabetes reduces long-term complications, and the American
Diabetic Association currently recommends that the Hgb A1c be <7%.
If a patient has a history of thrombosis in any venous or arterial segment or a family history
of a clotting disorder, an evaluation for hypercoagulability is necessary. Tests include routine
prothrombin time, partial thromboplastin time, platelet count, Factor V-Leiden, Factor II
(prothrombin) C-20210a, anticardiolipin antibody, baseline protein C, protein S, and
antithrombin III.
Imaging
Imaging is as follows.
Contrast aortography is not always required, unless interventional therapy (percutaneous
transcatheter angioplasty [PTA]/stent or surgical revascularization) is planned. Serum
creatinine is checked to validate a baseline level prior to the use of contrast agents that may
be nephrotoxic. CT angiography of the aorta is less invasive and shows high resolution for
aortic occlusive problems, but in patients with impaired renal function it should be avoided.
As an alternative to conventional angiography, magnetic resonance angiography or arterial
duplex mapping as a definitive imaging study for planning treatment may be considered. To
derive the best information about the needs of the patient, careful consideration of the clinical
picture should be assessed, in order to request these studies.
Other Tests
Other possible tests include the following.
The Doppler-derived ankle-brachial index (ABI) is a simple office-based examination that will
confirm the diagnosis of PAD if the value is <0.9. The ABI also can grade the severity of
PAD. Note that Doppler-derived segmental arterial pressures do not reflect the severity of
aorto-iliac
occlusive disease accurately. Moreover, if the blood pressure cuff is unable to compress the
vessels adequately, the Doppler-derived pressures may be falsely elevated. This may occur
in patients with diabetes or end-stage renal disease. In the event that supranormal (falsely
elevated) Doppler-derived pressures are encountered, pulse volume recordings may be
useful in evaluating leg perfusion. The pulse volume recording waveform reflects the volume
of blood in the leg during an individual cardiac cycle. A normal waveform demonstrates a
brisk upstroke, a sharp systolic peak, and a downstroke with a dicrotic notch. With significant
PAD, the dicrotic notch is lost, the slope of the upstroke and downstroke decline, the
amplitude of the waveform is reduced, and the contour of the systolic peak is more rounded.
Because an association of coronary disease and PAD exists, an electrocardiogram should be
obtained even in patients without a cardiac history.
For patients being considered for an intra-abdominal aortic procedure, pulmonary function
tests are important if a history of obstructive pulmonary disease or dyspnea is present. Many
times the therapeutic approach will need to be altered based on the results of this
preoperative evaluation. Endovascular procedures are more likely to be performed without
problems in patients with chronic obstructive pulmonary disease.
Techniques
An aortic stenosis, in general, can be approached from the femoral arteries. Bilateral
percutaneous punctures are usually necessary. Catheterization of the abdominal aorta through
the stenosis or occlusion requires a steerable guide wire and/or a multipurpose-Type catheter.
Once the obstruction is crossed and a catheter is above the obstruction, a stiff guide wire
should be introduced from both sides. Although angioplasty has been shown to be quite
effective, the risks of distal embolism are much higher than with primary stenting. Besides, the
long-term success of stenting has been shown to be excellent, therefore, most aortic stenoses
requiring treatment should be stented. If the lesion is very distal, close to the aortic bifurcation,
kissing balloon angioplasties and stenting should be performed, shifting the aortic bifurcation to
a higher position. If the lesion is more proximal in the infrarenal aorta, it may be treated with a
single larger balloon. The larger balloons have a much smaller profile than years ago, and a 7-
to 8-Fr sheath may be enough to accommodate a 14- to 18-mm balloon for angioplasty.
Modern balloon expandable and self-expandable stents have a lower profile and can be
introduced through smaller sheaths. Occasionally a femoral cutdown may be necessary for
introducing a Giant Palmaz stent, but nowadays even large sheaths, 14 to 18 Fr, can be used
percutaneously with preclose technique using the percutaneous suturing devices. The larger
balloon expandable stents may require a long sheath to protect the stent all the way up to the
stricture site. The angioplasty balloons need to be carefully inflated, making sure the bifurcation
of the aorta is cleared and the large balloon is above the level of the common iliac artery. If an
oversized balloon is inflated within the common iliac artery, there is a significant risk of acute
rupture of the artery and massive retroperitoneal bleeding. Predilation of the aortic stenosis
may not be necessary and primary stenting may be an option. Self-expandable stents usually
have a lower profile for introduction but have a lower radial force and may not be effective to
properly treat some aortic stenoses that may recoil.
Once the stent is placed and dilated to the final size, an aortogram should be acquired to verify
complete expansion and coverage of the lesion in its entirety. Intravascular ultrasound may be
helpful to define the area to be covered, as well as to verify contact of the stent with the aortic
wall. The thrombosed aortas require some form of thrombolytic therapy or thrombectomy, prior
to the angioplasty and stenting procedure, as described above.
More recently, there have been reports of management of aorto-iliac disease with bifurcated
stent-grafts (46,47). According to this experience the aorto-iliac reconstructions remain patent
during a midterm follow-up, with stable ABIs. There is no reported mortality or amputation
reported in the published series, suggesting that the endovascular placement of a bifurcated
stent-graft is technically feasible, effective, and safe for the management of aorto-iliac
occlusive disease. Some bifurcated stent-grafts can be placed percutaneously, but the decision
depends on the quality of the arteries available for access.
Outcomes and Prognosis

Open Surgery Treatment
Outcomes following aortic operations for aorto-iliac occlusive disease are measured in terms of
operative mortality rates and patency of the arterial reconstruction over time. These outcomes
are similar for aorto-iliac and AFB. The operative mortality rate (30 days) is about 2% to 3%.
Long-term patency is excellent too. The patency rate at 5 years following AFB is 85% to 90%.
If patients continue to smoke, however, the excellent patency rates may be reduced by half
(48).
Outcomes for extra-anatomic (axillofemoral/femorofemoral) bypasses clearly are not as good
as for AFB. Operative mortality rates for extra-anatomic bypass might be expected to be better
than for AFB due to the extracavitary nature of these procedures and the fact that aortic
clamping is not required during the course of the operation. However, the operative mortality
rate of 0% to 4% for femorofemoral bypass and 2% to 11% for axillobifemoral bypass is a
reflection of the selected patients in whom these procedures are performed. Five-year primary
patency of extra-anatomic bypasses performed for aorto-iliac occlusive disease ranges from
19% to 50% for axillobifemoral bypass and 44% to 85% for femorofemoral bypass (49). More
recently total laparoscopic bypass for aorto-iliac occlusive disease has been used in hopes of
improving morbidity and mortality related to the procedure, but the mortality is still about 4%,
the procedures are prolonged, and complications include colonic ischemia, multiorgan failure,
and other nonlethal major complications such as spleen rupture and graft infection (50).
Endovascular Treatment
Endovascular techniques (i.e., PTA and stent placement) offer alternatives to conventional
surgical repair (Fig. 12-14). Therefore, understanding the outcomes offered with such
interventions is important. Although isolated stenosis of the infrarenal aorta or common iliac
artery is uncommon, this lesion is suited ideally to PTA and/or stent placement. With localized,
segmental occlusive disease in the aorta, initial technical success can be achieved in more than
95% of cases, with 5-year patency rates of 80% to 87% using PTA. Initial success rates using
PTA for iliac lesions are 93% to 97%, with 5-year patency rates of 54% to 85%. These results
seem to be improved when arterial stents are used either primarily or as an adjunct to PTA for
the treatment of iliac artery stenosis.
FIGURE 12-14. A: Aortogram showing an 80% stenosis in the infrarenal aorta, just below
the origin of the inferior mesenteric artery (IMA). B: Balloon angioplasty followed by
placement of a large Palmaz stent was performed, with total resolution of the stenosis. C:
Aortogram after treatment showed a patent aorta, with persistent patency of the IMA and
the lumbar arteries.
FIGURE 12-15. A 48-year-old man with coronary artery disease developed acute
occlusion of the abdominal aorta and severe ischemia of the legs. Emergency treatment
was undertaken. A: Left femoral approach with catheterization across the clot in the iliac
artery and aorta, followed by aortogram, showed occlusion of the distal aorta, extending
into the common iliac arteries. B: Late phase of the aortogram showed recanalization of
the iliac arteries. C: Pulse-spray of urokinase was performed at 250,000 IU, followed by a
100,000 IU/hour infusion for 15 hours. Follow-up aortogram showed good recanalization of
the aorta and partial reopening of the iliac arteries. D: Continued infusion for 9 more hours
further improved the patency of the iliac arteries. The persistent filling defect in the left iliac
artery was treated with the Amplatz mechanical thrombectomy. E: Final aortogram showed
adequate patency of the aorta and both iliacs. Note the persistent occlusion of the left
internal iliac artery.
Aortic PTA has a primary success rate of 95%, ranging from 83% to 100%. At 1 year the
success rate is 98%, ranging from 83% to 100%. At 3 years the success rate is 87%, ranging
from 83% to 96%. At 5 years the success rate is 80%, ranging from 70% to 92% (51). In
another series of 78 patients, initial success was 100% and at 10 years 72% were patent (52).
In a comparative study of endarterectomy versus angioplasty in the treatment of localized
stenosis of the abdominal aorta, endarterectomy proved to be safe and effective for treating
AOD limited to the distal aorta, while balloon angioplasty alone appeared to be less reliable
(53). Despite the disadvantage, PTA was recommended as the initial treatment of choice due to
the less invasive nature of the disease, in patients with anatomically suitable lesions and with
higher surgical risk (53).
Stent placement in the abdominal aorta may be considered in two different settings: (a) as a
primary treatment (Fig. 12-14) and (b) as a secondary intervention after early or late PTA
failure. The differences in success rate and long-term outcomes are not clearly defined as yet
(54) but the need for stenting is very clear when there is a residual pressure gradient (>10 mm
Hg), recoil, or restenosis. Initial success for aortic stenting in focal lesion of the infrarenal aorta
was 100%. Three-year primary patency was 85%, and 3-year secondary patency was 100%
(55). There was no mortality, and the morbidity was limited to puncture infection,
pseudoaneurysm, and distal embolism. In another series of 13 patients, the initial success rate
was 100%, the 4-year patency rate was 100%, and there was no mortality. There was low
morbidity, with hematoma at the puncture site in two patients. Aortic stenting in 11 patients had
a technical success rate of 100%, 3-year patency rate of 91%, and 3-year secondary assisted
patency rate of 100% (56). Aortic PTA and stenting in 86 patients had a 1-year primary
patency of 94%, 3-year primary patency of 89%, and 5-year primary patency of 77% (57).
Complete coverage of the treated stenotic segment with endothelium is the main goal of
endoluminal stent placement for prevention of low-flow thrombosis (1). However, irregular
ulcerated lesions may cause thrombus formation and distal embolization during manipulation or
after stent placement. Infusion of short-term lysis in cases of ulcerated plaques may reduce the
risk of thromboembolism. In general, there is no difference between the self-expanding and the
balloon expandable stents, and the main complication is related to the puncture site due to the
large size of the delivery systems. Occlusion of the inferior mesenteric artery is a possibility
when an intra-aortic stent is placed, but it does not necessarily lead to mesenteric ischemia (1).
Endovascular therapy for aortic occlusion may be used successfully in chronic and acute cases.
As described above, chronic cases of aortic obstruction or stenosis are related to lower
extremity claudication and acute occlusions in general present with acute pain, lower extremity
ischemia, and sometimes paralysis. The use of thrombolytic therapy, mechanical
thrombectomy, and stenting may take care of most cases, with resolution of symptoms (Figs.
12-15 and 12-16).
The endovascular treatment of aortic occlusions or stenosis has a high technical success rate
(close to 100%) in most series and has very promising midterm results (1,51, 52, 53, 54, 55,
56, 57, 58, 59, 60), providing a real alternative to open surgery for most patients.
FIGURE 12-16. A 48-year-old male patient with previous BKA on the right side and AKA on
the left side due to chronic vascular occlusive disease developed acute occlusion of the
abdominal aorta, causing severe lumbar pain and paresthesia below the waist level. A, B:
Abdominal aortogram performed through the left brachial approach showed a totally
occluded abdominal aorta, with partial reconstitution of the left external iliac and distal
branches. Direct access to the aorta was obtained from the right femoral artery and
infusion of thrombolytic therapy was performed with Retavase. C: Injection of contrast
material at the aortic bifurcation showed bilateral thrombosis of the iliac arteries. D:
Follow-up angiogram showed partial recanalization of the right iliac artery and E: injection
into the aorta showed partial recanalization of the distal aorta with spasm or thrombus in
the mid-superior mesenteric artery. F, G, H: Follow-up angiogram of the aorta and iliac
arteries after continued therapy showed improved recanalization. I, J: Final aortogram
showed patency of the aorta and iliac arteries, with an occluded common femoral artery.
K: Intravascular ultrasound of the aorta showed a large atheromatous plaque in the
immediate vicinity of the right renal artery. Note the large plaque just below the right renal
artery at 2 to 4 o'clock. L: Follow-up magnetic resonance angiography of the treated
aorta, 6 months after treatment. Note the distally occluded left iliac artery, and the filling
defect within the aorta, in a juxtarenal position. Nevertheless, total resolution of the
symptoms was observed.

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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 13 - Mesenteric Ischemia
Chapter 13
Mesenteric Ischemia
Renan Uflacker
Mesenteric ischemia (MI) is caused by a decrease in the availability of oxygen to intestinal
tissue that is caused by inadequate blood flow to the mesenteric arteries. MI may be acute or
chronic.
Acute MI may develop due to abrupt occlusion of one or more major splanchnic arteries or due
to poor perfusion (low flow) without occlusion. Acute occlusive MI is in general caused by
embolism or mesenteric artery thrombosis (1). Nonocclusive MI is caused by poor perfusion,
and spasm of the mesenteric territory due to a low-flow state (2). This nonocclusive
phenomenon is usually related to cardiac and systemic circulatory deficits, including reduced
cardiac output, congestive heart failure, hypotension, shock, and vasoconstriction (3). Chronic
MI results from progressive stenosis or occlusion of one or more visceral arteries, and the most
common cause is atherosclerotic disease (4).
While the chronic condition is usually related to postprandial pain, associated fear of eating, and
diarrhea, it is only occasionally life-threatening. Occasionally, this condition may evolve into an
acute situation with bowel necrosis (5). Acute MI, on the other hand, has a much more dramatic
onset, leading to intestinal infarction and possible necrosis in a mater of hours and carrying a
high morbidity and mortality (5).
Collateral Circulation Pathways and Autoregulatory

Mechanisms
The intestinal circulation has abundant collateral pathways designed to protect the gut from
ischemia, to a limited extent, particularly in chronic situations (Fig. 13-1). However, when the
superior mesenteric artery (SMA) occludes acutely, the collateral circulation usually responds
poorly to the changes in blood pressure in the distal splanchnic vascular bed, developing
vasoconstriction and reduction in distal blood flow. Nevertheless, the mesenteric circulation has
autoregulatory mechanisms that are influenced by local and systemic factors (6). The local
factors are vasoactive tissue metabolites (lactic acid, CO2, Adenine nucleotides, prostaglandin,
and bradykinin), bloodborne vasodilators, and endotoxins (tumor necrosis factor). Systemic
factors are related to the autonomic nervous system (ANS: sympathetic, vasoconstriction;
parasympathetic, vasodilation), bloodborne vasoactive substances (catecholamines,
angiotensin II, histamine, serotonin, and vasopressin), myogenic response (intrinsic vascular
smooth muscle regulation), and oxygen saturation. Other systemic events, such as changes in
the cardiac output, systemic arterial pressure, venous pressure, blood volume, and blood
viscosity, are cardiovascular factors that also play an important role in moderating bowel
perfusion (5). In the normal resting state, the splanchnic circulation receives about 25% to 28%
of the cardiac output; any major reductions are mostly related to increased sympathetic activity,
which promotes vasoconstriction and increases distal resistance (7).
Anatomy and Pathophysiology of the Mesenteric Circulation

Gut ischemia may result from a reduction in mesenteric perfusion, redistribution of blood flow,
or a combination of both. Systemic hypotension and/or shock is associated with a decrease in
the splanchnic blood flow due to distal vasoconstriction as well as arteriovenous shunting within
the bowel wall away from the mucosa and muscularis propria (Fig. 13-2). The intestinal
vascular system is made up of several circuits coupled in parallel (8). Each circuit is located in
the layers of the intestinal wall such as the mucosa, submucosa, and muscularis. Each circuit
has segments coupled in series, namely, the resistance vessels (arterioles), the precapillary
resistance segment (precapillary sphincters), the exchange vessels (capillary), the postcapillary
sphincters, and the capacitance vessels, which contain the major part of the regional
(mesenteric) blood volume (veins and large venules). The balance between the pre- and the
postcapillary sphincters determines the mean hydrostatic pressure and the direction and
magnitude of the net fluid movement across the capillary wall in the exchange vessels. In
reality, however, there are no anatomical sphincters, and the word sphincter is used only to
designate a functional entity. The exchange segment is the one in which the important exchange
of fluid and metabolites takes place. Due to the large volume of the visceral capillary bed and
the increased capillary permeability, compared to skeletal muscle capillaries, the balance
between the pre- and the postcapillary resistance is critical to prevent fluid losses. The need to
maintain a sufficient driving force for blood to reach the liver, crossing the mesenteric vein and
portal circulation, requires a relatively high venous pressure at the level of the intestinal veins,
adding to the critical role of the pressure/permeability balance (9). The redistribution of the
blood flow may be dramatic, by arteriovenous shunting within the bowel wall during intestinal
distention with bowel wall stretching and thinning. When an intraluminal bowel pressure of >30
mm Hg is reached, the splanchnic blood flow will be reduced, in both the small and the large
intestine. However, even at intraluminal pressures of 210 mm Hg, 20% to 35% of baseline
blood flow will still be maintained. Intramural shunting also explains why serosal vessel
perfusion produces an external normal, pink-looking appearance of the bowel, even with
reduction of the blood flow to levels as low as 20% of normal, while hemorrhagic infarction is
already present in the mucosa. The effect of intermittent distention of the small bowel is also
significant, reducing blood flow to the entire small bowel, not just to the affected segment, and
this change in flow may persist for hours, even after relief of the distension.
It is important to understand the role of sympathetic nerve stimulation, hypotension, and
hypovolemia in the development of acute MI (9,10). Sympathetic nerve stimulation or
vasoconstrictive agents (noradrenaline, for example) do not change the equilibrium across the
capillary wall, even with reduced blood pressure or in shock. In the gut, sympathetic nerve
stimulation
induces prompt vasoconstriction, which ends after a minute or so, despite continuous
stimulation, due to autoregulatory escape from the response. This is followed by a paradoxical
reactive hyperemia response, which is also known as tachyphylaxis. Other vasoconstrictors,
such as angiotensin and vasopressin and their derivatives, do not cause tachyphylaxis, and this
is why these drugs are used for the treatment of GI bleeding through vasoconstriction.
FIGURE 13-1. Angiogram of the inferior mesenteric artery in a case of proximal occlusion
of the superior mesenteric artery (SMA) demonstrating the wide anastomosis between the
two systems through the marginal artery of Drummond and the arc of Riolan. The middle
colic artery branch of the SMA is enlarged.
FIGURE 13-2. The gastrointestinal vascular system at the level of the bowel wall is
composed of three compartments with circuits coupled in parallel. The regulation of the
blood flow is done by the adjustable resistance at the arterial side and sphincteric
mechanisms and small adjustable resistance at the venous side.
The volume of blood contained in the capacitance vessels of the bowel wall is reduced by 40%
in response to gastrointestinal (GI) vasoconstriction from nerve stimulation (7). This
phenomenon produces the autotransfusion observed in humans, during which a half a liter of
blood or more is delivered to the systemic circulation as the first response to hypovolemia.
However, during episodes of hemorrhage or in sepsis, mesenteric blood flow is reduced
proportionally to the drop in cardiac output. Therefore, with significant loss in total blood volume
(>35%), a significant and disproportionate visceral vasoconstriction ensues. This response is
more likely to be related to the renin-angiotensin axis and is blocked effectively by renin-
angiotensin mechanism blockers such as enalapril.
The bowel mucosa is the most sensitive segment to ischemia. Even in situations of SMA
blockage or low mesenteric flow, a larger fraction of the intestinal blood flow is directed to the
intestinal mucosa. However, when there is persistent inadequacy of the blood flow to the
intestinal mucosa, ischemia will result, and necrosis may develop. The culprit for the start of the
intestinal necrosis in the mucosa is the oxygen countercurrent phenomenon at the level of the
intestinal villus (11). The anatomy of the intestinal villi is such that the inflow arteriole and
outflow venule are separated by a space of just 10 m (Fig. 13-3). The arteriole does not
branch until it reaches the tip of the villus and the blood is transported back to the base of the
villus in a more superficial network of vessels parallel to
the artery. During slow flow or low arterial pressure the short distance between the arterial and
the venous vessels allows diffusion of O2, short-circuiting the passage of O2 through the
capillary bed in the tip of the villus. The low saturation of O2 causes hypoxia and necrosis of the
tip of the villus when the flow is <150 ml/100 g/minute in the SMA. Additionally, when the
systolic pressure is <60 mm Hg, there is arteriolar muscle relaxation, leading to vessel collapse
and flow cessation, with a further drop in the blood pressure within the SMA (critical closing
pressure) (7). Vasoconstriction is observed throughout the mesenteric circulation in acute
intestinal ischemia regardless of the cause. The result of MI may be a spectrum ranging from
reversible functional alterations to total hemorrhagic necrosis of portions of the bowel or its
entirety.
FIGURE 13-3. Schematic drawing of an intestinal villus showing the venules, the arteriole,
and the lymphatic vessels. Note the close relationship of the vessels in the center of the
villus, where the oxygen countercurrent phenomenon occurs. As the inflow and outflow
capillaries are separated by just 10 m, it allows diffusion of O2, thereby short-circuiting
passage through the capillary bed in the tip of the villus. This may cause hypoxia and
necrosis of the tip of the villus when the flow is slowed below a certain level.
TABLE 13-1 PROPOSED MECHANISMS FOR SYSTEMIC AND VISCERAL

EFFECTS OF MESENTERIAL ISCHEMIA
Systemic Release of cardiotoxic substances to the blood
Release of other toxic substances, including mediators
Translocation of bacteria and endotoxins
Visceral Hepatic consequences of gut ischemia
Effects of the gut as an immune organ
Local Increased gut mucosal permeability
SYSTEMIC AND VISCERAL EFFECTS OF MESENTERIC

ISCHEMIA
A number of cardiotoxic substances, mediators, bacterial endotoxins, and changes in gut
mucosal permeability are proposed mechanisms for systemic effects of intestinal ischemia (12)
(Table 13-1). Cardiac dysfunction is evident in cases of shock and MI. This is thought to be
related to the release of substances by the gut, causing a negative influence on the heart's
contractility. The small bowel has been accepted to be the site of origin of some cardiotoxic
factors, as well as circulating factors causing lung injury. Filtration techniques have shown the
molecular mass of the active substance to be 500 to 1,000 daltons (13), similar to the more
recently described myocardial depressant factor, which causes blockade of the calcium
channels of the myocardial cells (14). A number of other toxic factors released by the GI tract
following hypotension and shock, with the potential to cause pulmonary injury, have been
described. Proteases, tumor necrosis factor , and interleukins are some of the factors
produced by intestinal macrophages (15,16).
FIGURE 13-4. A: Early phase of a SMA angiogram during an episode of acute
nonocclusive mesenteric ischemia shows generalized vasospasm of the mesenteric
circulation. Note the significant bowel dilation. B: Venous phase of the SMA angiogram
shows faint and asymmetric mesenteric venous return.
The intestinal mucosal injury related to hypoxia is initially confined to the more superficial parts
of the mucosa and is characterized by tissue edema and lifting of the epithelial cells at the tip of
the villi (17, 18, 19). The possible functional implications of superficial injury of the mucosa of
the GI tract are several. There is increased translocation of bacteria and endotoxins and
impaired absorption of fluids and food. Systemic introduction of bacteria and endotoxins from
the gut lumen may occur during shock states and, as previously recognized, influences the
outcome of the individual affected by ischemia (20). More recently the concept has been
revised and updated (21). Translocation is most likely related to changes in mucosal
permeability, but there are unknown factors related to the phenomenon. Translocation can be
directly to the venous portal venous blood flow, directly to the lymphatic route, or to the
abdominal cavity through the intestinal wall. Hence antibiotic therapy is necessary for all
patients with evidence of MI (22,23). There can also be loss of fluid into the gut lumen with
hemorrhage. The colon appears to be more resistant to ischemia than the small intestine and
stomach.
ACUTE MESENTERIC ISCHEMIA

Acute MI may be nonocclusive (splanchnic vasoconstriction, as in ergotism, and shock or low-
flow status, as in acute pancreatitis with fluid sequestration and myocardial infarction) (Fig. 13-
4), or occlusive (embolus, arterial, or venous thrombosis)
(Fig. 13-5). The acute onset of occlusive MI may be preceded by months or years of
symptoms of mesenteric angina, and up to 25% of patients being investigated for chronic MI
may develop acute symptoms (24).
FIGURE 13-5. A 78-year-old woman with severe abdominal pain, after acute myocardial
infarction and acute occlusive mesenteric ischemia. A: Selective SMA arteriogram showing
total occlusion of the proximal segment of the artery by an acute embolus, with marked
spasm of the patent branches above and beyond the obstruction. Note reflux into the aortic
lumen. B: Post-papaverine bolus injection (100 mg) SMA angiogram shows persistent
occlusion of the artery but with significant vasodilation of the SMA branches. Papaverine
infusion was maintained while the patient was prepared for surgery.
Clinically, acute MI is associated with pain, vomiting, diarrhea, and occult blood in the GI
content. Patients with acute abdominal pain associated with distension and a paucity of physical
examination findings should have a presumptive diagnosis of MI. A high degree of clinical
suspicion is necessary for an early diagnosis. Nevertheless, in approximately 50% of cases the
ischemia is nonocclusive and related only to slow flow and vasoconstriction, and this has to be
taken into consideration for the differential diagnosis (5,25).
There is no laboratory workup with enough sensitivity and specificity for the diagnosis of acute
MI (3). Early imaging is very important to identify occlusions of the main visceral arteries.
Emergency mesenteric angiography is the single most important way to diagnose acute MI (5).
The demonstration of mesenteric embolism, thrombosis, or slow flow with vasoconstriction is
diagnostic for the acute problem and catheterization provides access for intra-arterial treatment
with infusion of vasodilators or thrombolytic therapy (5). Infusion of a bolus of vasodilators may
provide clues for the efficacy of the treatment with papaverine infusion and may contraindicate
immediate surgical treatment in cases of low flow and vasoconstriction. Papaverine is
particularly useful for the treatment of nonocclusive MI, and the response to the bolus injection
gives a good indication for the best management (25). Later surgery may be necessary in
some of these patients for identification and resection of bowel necrosis.
Risk factors for acute MI include age >50 years, valvular or arteriosclerotic heart disease,
cardiac arrhythmia, hypovolemia or hypotension (such as in burns, pancreatitis, GI bleeding, or
postoperative hemorrhage), recent myocardial infarction, long-standing congestive heart failure,
especially with unsatisfactory control of digitalis therapy, or prolonged use of vasopressor
drugs and or diuretics (25).
Typically, the sequence of events starts with acute arterial blockage or an acute low-flow state,
followed by ischemia, infarction, and tissue death. Acute MI requires prompt suspicion of the
diagnosis and emergency action, which includes angiography to evaluate the splanchnic
circulation to rule out nonocclusive MI (low-flow state), which is a common presentation (50%),
or to confirm embolism. Mesenteric angiography very effectively evaluates embolism and SMA
occlusion, prompting the use of vasodilator infusion followed by surgical embolectomy. A
negative mesenteric angiogram securely excludes the diagnosis of ischemia. Acute MI of any
cause has a reported mortality rate of 70% to 90% if left untreated and may be reduced to
~50% if treated early (25).
ACUTE NONOCCLUSIVE MESENTERIC ISCHEMIA

Acute nonocclusive MI, usually affects older patients (>50 years), with abrupt or insidious onset
of abdominal pain, which may be preceded by chronic or episodic abdominal pain. Causal
factors are various and include congestive heart failure (reduced cardiac output leading to
reduced mesenteric flow), myocardial infarction, aortic insufficiency, renal and hepatic disease,
cardiac arrhythmia, pulmonary edema, digitalis therapy (particularly overdose),
hemoconcentration, trauma,
shock, sepsis, bowel distention (Fig. 13-6), major surgery, profuse diarrhea (bleeding) or
vomiting, and hematemesis (rare) (25). The complex pathogenesis is most probably related to
splanchnic vasoconstriction occurring in response to a number of factors, including a decrease
in cardiac output, hypovolemia, dehydration, vasopressor agents, and hypotension. The
vasoconstriction may persist even after correction of the cause is achieved. In addition, the
intestinal ischemia may paradoxically manifest hours or days after the ensuing of the cause.
Due to the facts presented above, the management of nonocclusive MI always involves
treatment of causative factors that contribute to the circulatory insufficiency (26,27).
FIGURE 13-6. A young patient with sepsis and dehydration presented with abdominal pain
and distension with advanced low-flow (nonocclusive) mesenteric ischemia. A: Distended
stomach with significantly reduced arterial flow from the left gastric artery and the
gastroduodenal artery demonstrated during the celiac artery injection. Note the shutdown
of the splenic arterial circulation. B, C, D: SMA angiogram shows reduced or absent
circulation in several areas of the small bowel with perfusion of the right colon. There is
some degree of bowel wall enhancement with shunting and early filling of some veins.
Angiographic Findings of Nonocclusive Mesenteric Ischemia

The angiographic signs of nonocclusive MI include diffuse spasm or vasoconstriction of the
SMA, focal spasm at the origin of major branches of the SMA, and multiple areas of
intermittent spasm and dilatation (string of sausages) (Fig. 13-7). Peripherally one may
identify narrowing, irregularity, and occlusion of smaller SMA branches. Impaired filling of
intramural vessels with a pruned appearance of the mesenteric branches is also seen in some
cases (Fig. 13-8) (25, 26, 27). However, mesenteric vasoconstriction may occur in other
situations, such as hemorrhage and pancreatitis, and the causal problem may be
angiographically diagnosed as well.
ACUTE OCCLUSIVE MESENTERIC ISCHEMIA
The clinical presentation of acute occlusive MI is usually more abrupt and severe but may be
very similar to that of nonocclusive MI. Peritoneal signs are indicative of advanced and, most
likely, irreversible bowel ischemia, with infection or perforation. The most common cause is
embolism, in about
50% of cases (Fig. 13-5), and related to mitral valve disease, atrial fibrillation, rheumatic, and
valvular disease. Primary arterial thrombosis is also frequently encountered preceded by a
semiocclusive atheromatous plaque (28) (Fig. 13-9). Hemorrhagic infarct may complicate
chronic bowel ischemia and precipitate a fatal outcome. Prompt diagnosis and emergency
action are also necessary in those cases and comprehensive angiographic workup is important
to confirm the diagnosis of an acute thrombosis or and to exclude synchronous emboli in other
abdominal aorta branches, which is present in about 20% of patients. Acute SMA thrombosis is
less frequent than acute embolism, is almost always superimposed on chronic atherosclerotic
narrowing of the ostium of the SMA, and is preceded by chronic abdominal pain in most cases.
If angiography identifies large, well-developed collaterals, the occlusion can be considered
chronic, while the absence of collateral
vessels denotes the likelihood of an acute occlusion by thrombosis, requiring prompt
intervention (28).
FIGURE 13-7. SMA angiography was performed in a female patient with myocardial
ischemia followed by significant abdominal pain. A: The angiogram shows the typical
pattern of a string of sausages, with areas of stenoses (spasm) and dilations in the
branches of the SMA. B: The late-phase angiogram shows present, but faint filling of the
superior mesenteric vein and portal vein. The diagnosis of nonocclusive MI was made and
papaverine infusion was started at 60 mg/hour. C: SMA angiogram after 20 min of infusion
treatment shows resolution of the string of sausages pattern and improvement of bowel
perfusion. D: Late-phase SMA angiogram shows significant improvement of the mesenteric
venous circulation.
FIGURE 13-8. A: Diffuse vasoconstriction in a case of nonocclusive mesenteric ischemia in
a patient with massive miocardial infarction and congestive heart failure was treated with
80 mg of papaverine followed by infusion of 60 mg/hour for 24 hours. B: SMA angiogram
shows improvement of the mesenteric circulation after the bolus injection. C: Follow-up
SMA angiogram after 24 hours of infusion shows significant improvement of the mesenteric
circulation with intestinal perfusion, with resolution of the abdominal pain and distension.
Angiographic Findings in Acute Occlusive Mesenteric

Ischemia
Arterial emboli show a sharp, rounded filling defect with a convex meniscuslike appearance in
the early angiographic phase. The embolus tends to stop at points of normal vascular narrowing
or bifurcation of the vessel (Fig. 13-10). In general, SMA emboli stop just above the origin of
the inferior pancreaticoduodenal artery, but in about 10% or more of patients, there are emboli
that are more peripheral (26, 27, 28). A computed tomography (CT) angiogram in these cases
may be enough for the diagnosis but will not help in the treatment (Fig. 13-11). Transcatheter
infusion of vasodilators and thrombolytic therapy may help these patients, while emergency
surgery is arranged, and in most cases surgical treatment with SMA bypass and/or
embolectomy is necessary (Fig. 13-5).
The presence of pneumatosis intestinalis or the presence of gas within the portal vein, although
indicative of MI, also indicates the presence of intestinal necrosis that is irreversible and
advanced, carrying a somber prognosis.
FIGURE 13-9. A patient with chronic mesenteric angina developed acute abdominal pain.
A: Lateral view of abdominal aortogram with proximal occlusion of the SMA. Note the faint
distal reconstitution. The abdominal aorta shows diffuse atherosclerosis and the celiac
trunk is also narrowed. B: Selective injection in the celiac artery shows very little
collateralization to the SMA, suggesting an acute occlusion. C: Selective injection shows
near-occlusion of the SMA. D: Multiple attempts to cross the obstruction were performed
and eventually a guide wire and a small 4-Fr catheter was passed across the occlusion.
Injection shows patency. E: A 4-mm angioplasty was used for predilation. F:
Postangioplasty angiogram shows minimal improvement of the stenosis. An attempt was
made to place a balloon expandable stent to cross the SMA occlusion but failed. The stent
was removed. The patient became unstable and the procedure was aborted to be
reattempted in 12 hours. The patient persisted with abdominal pain, and massive necrosis
of the small bowel was verified at surgery, followed by death.
FIGURE 13-10. A, B: Intracardiac thrombus embolized to the SMA in a patient with atrial
fibrillation. Note fragmentation of the thrombus within the SMA and stopped at the
bifurcations and origin of mesenteric branches. Papaverine infusion was performed,
followed by urokinase (UK) infusion of 100,000 IU/hour for 17 hours. C, D: Follow-up
angiogram after 17 hours of UK infusion shows improvement. E, F: Follow-up angiogram,
40 hours after infusion of UK, shows adequate patency of the SMA and mesenteric
branches. Note the filling of the superior mesenteric vein and portal vein in F, compared to
B. This particular patient did not need surgical inspection or bowel resection.
Management of Acute Mesenteric Ischemia

Patients with symptoms of acute MI should be rapidly evaluated for the risk factors, such as
age (>50 years), presence of valvular or arteriosclerotic heart disease, long-standing
congestive heart failure, cardiac arrhythmias of any cause, hypovolemia or hypotension, and
myocardial infarction. Patients with any of these risks, who have sudden abdominal pain for
more than 2 or 3 hours, should be managed promptly and aggressively. The high negative yield
of the prompt angiographic evaluation is acceptable since waiting for more extensive and
specific signs and symptoms of ischemia usually results in irreversible intestinal damage and
high mortality (25, 26, 27, 28).
A decision to operate on the patient does not preclude the performance of an emergency
angiogram, which often helps define the correct diagnosis and can potentially be useful for
initiating transcatheter intra-arterial infusion of vasodilators (Fig. 13-5) or thrombolytic drugs
(Fig. 13-12). Simultaneous correction of the predisposing or precipitating causes of MI should
be initiated. Replacement of blood volume and stabilization of the cardiopulmonary status
should precede any diagnostic studies. Mesenteric vasoconstriction will be
angiographically evident in patients in shock, with or without intestinal ischemia. Vasopressors
are contraindicated if the treatment of shock if MI is suspected. The presence of intestinal
ischemia should prompt aggressive appropriate correction of plasma volume deficits and fluid
loss, as well as GI decompression and antibiotic therapy (25).
Imaging should be used to exclude other causes of abdominal pain, such as intestinal
perforation and obstruction. Angiography must be performed emergently for the diagnosis of
mesenteric artery obstruction or low-flow status, and therapeutic infusion of papaverine should
be started regardless of the cause of ischemia. We perform a test with the intramesenteric
injection of 80 mg of a papaverine bolus. If resolution or improvement of the vasospasm is
observed, continuous infusion of papaverine is started (for low-flow status and in distal
occlusions) at a rate of 30 to 60 mg/hour (25). In proximal SMA occlusion, mechanical
thrombectomy, thrombolytic therapy, balloon angioplasty, and stent placement are options for
selected patients, followed by papaverine infusion (Figs. 13-10, 13-11 and 13-12). Heparin
should be avoided in some cases to prevent GI bleeding due to reperfusion, and when used, it
should not be mixed with papaverine, to avoid precipitation of the drugs. The patient should be
monitored in an intensive care unit. However, since >90% of the papaverine infused within the
SMA is metabolized on first pass through the liver, there is a negligible expected rate of
systemic hypotension and cardiac arrhythmias.
The length of the papaverine infusion varies according to the purpose and patient's response.
When papaverine is used as primary treatment for nonocclusive MI, it is continued for about 24
hours, and a follow-up angiogram should be performed before a decision is made regarding
continuing or stopping the treatment (25). Based on clinical course and improvement of
vasoconstriction, the infusion is discontinued or continued for an additional 12 to 24 hours.
When the infusion is used in conjunction with laparotomy for nonocclusive ischemia, a second-
look surgery is frequently necessary. When the vasoconstriction is resolved the infusion is
discontinued and the catheter removed.
When the infusion is used in conjunction with embolectomy and/or arterial reconstruction, in
cases of occlusive MI, papaverine treatment should be continued after the operation for 12 to
24 hours, especially if a second-look operation is not planned. After the 12- or 24-hour infusion
time an angiogram is obtained, and unless evidence of vasoconstriction is still noted, the
infusion can be discontinued. If a second-look operation is planned, the infusion is continued
until the abdomen is reopened. In some cases it is beneficial to continue the papaverine infusion
after the laparotomy, depending on the status of the bowel loops and the results of the
preoperative angiogram. In most cases of SMA embolism, immediate surgical embolectomy is
indicated. Occasional bypass for revascularization may be used. If there is a question of bowel
viability, a surgical second look is performed within 24 hours regardless of the infusion of
papaverine.
The role of thrombolysis in the treatment of acute MI secondary to an embolus is still not very
well defined and should be evaluated individually. Thrombolytic therapy may be used in selected
patients who do not have peritoneal signs or elevated lactic acid levels. Selective intrathrombus
infusion is preferred, potentially helped by some form of mechanical or rheolytic thrombectomy
to accelerate the debulking process. However, care should be exercised during reestablishment
of flow, since the sudden release of ischemic by-products into the systemic circulation can lead
to acute respiratory distress syndrome and multiple organ failure. A fragmented thrombus
migrating to the distal circulation carries the risk of intestinal necrosis.
Outcomes of the Endovascular Treatment of Acute

Mesenteric Ischemia
The mortality rate of acute MI has been traditionally high, 70% to 90%, using the traditional
methods of diagnosis and treatment. The picture changed when the aggressive endovascular
protocol described by Boley in publications from 1973 and 1977 started to be used more
systematically (1,25). A 55%
survival was obtained when the management included the combination of early diagnosis and
aggressive diagnostic and therapeutic angiography with vasodilator infusion and early surgical
intervention when necessary (25). Patients managed by traditional methods maintained a
limited, 20% survival. Interestingly enough, about 70% of patients with SMA embolism treated
with the aggressive endovascular protocol within 12 hours of the beginning of the abdominal
pain survived. The acute MI related to low-flow status is more difficult to treat and has a worse
prognosis due to the systemic component involvement, which is more prominent than in
occlusive situations. The diagnosis of low-flow status is in general more difficult and patients
tend to be sicker when the problem is first recognized, leading to a higher mortality and
morbidity (25).
FIGURE 13-11. A patient with acute abdominal pain presented at the emergency room and
an emergency CT of the abdomen was performed. A: CT angiogram of the SMA showing
proximal patency. B: CT angiogram with a slice a few millimeters caudal shows occlusion
of the arterial lumen. C: A more distal CT angiogram slice shows reconstitution of the
luminal arterial flow. D: SMA angiogram shows abrupt occlusion of the SMA by an embolus
with a segment of occlusion. Note reconstitution of the distal SMA through the right colic
artery. E: Proactive mechanical thrombectomy with the Angio Jet device and infusion of
urokinase was performed, achieving recanalization of the occluded segment and
improvement of the bowel circulation. A segmental resection of small bowel was necessary
after several hours, but most of the bowel and the patient's life were spared.
MESENTERIC VENOUS THROMBOSIS
Acute mesenteric venous thrombosis is a distinct cause of MI, which is responsible for only a
small portion of the cases. Clot
presented in the mesenteric venous system in 1.5% of autopsies in one series (29), but
mesenteric vein thrombosis can account for up to 6.2% of cases of acute MI (30). A great deal
of confusion between slow-flow, nonocclusive MI and acute mesenteric venous thrombosis is
evident in the older literature and textbooks. Surgical inspection in those cases showed a patent
artery and evidence of intestinal infarction associated with a collapsed mesenteric vein due to
the low flow, suggesting a venous problem. Currently it is assumed that most of the cases
thought to be caused by mesenteric venous thrombosis were in fact caused by vasoconstriction
and low flow. Portal vein thrombosis also affects this population of patients, as an extension of
the superior mesenteric vein (SMV) thrombosis or as the primary event leading to mesenteric
vein thrombosis. The portal vein occlusion, depending on the degree and location, can cause
portal hypertension and, when extending into the SMV, cause occlusion of the small mesenteric
veins and mucosal and submucosal venous congestion causing the symptoms of MI. Therefore,
a distinction has to be made between patients with SMV thrombosis and patients with portal
vein thrombosis, and the management adjusted to one or the other situation. However, patients
with either one of the problems may evolve to an acute situation with portal hypertension
symptoms (bleeding, ascites) or MI with bowel necrosis.
FIGURE 13-12. A female patient with atrial fibrillation presented with acute abdominal pain.
A, B: AP and lateral views of the abdominal aortogram shows a large filling defect in the
proximal SMA and slow flow into the distal artery due to embolism. C, D: AP and lateral
views of the selective SMA angiogram shows occlusion of the proximal artery and distal
ileocolic artery. Urokinase (UK) infusion was performed for 8 hours, with a reduction in size
of the clot and improvement of perfusion, but there was also clinical improvement. E, F:
Final angiogram follow-up after 24 hours of UK treatment shows complete resolution of the
thrombus, with total resolution of the symptoms.
Causes for acute mesenteric venous thrombosis are most frequently related to hypercoagulable
states, and indeed 69.6% of the cases in one series were diagnosed with conditions such as
deficiencies of antithrombin III, protein S, or protein C, mechanical or inflammatory causes,
such as acute and chronic pancreatitis, malignancies, and use of clot-inducing medications such
as tamoxifen and estrogen. In its more severe forms, the presentation is acute, but milder than
that of arterial occlusion, usually with abdominal pain with progressive signs and symptoms of
bowel infarct. In general, however, most cases are more indolent and less specific in symptoms
than acute arterial mesenteric occlusion and the diagnosis is more difficult (Fig. 13-13). CT
angiography, magnetic resonance (MR) angiography and Doppler ultrasonography (US), and
digital mesenteric angiography can make the diagnosis with a greater degree of certainty than
in the earlier days, and usually can differentiate venous thrombosis from arterial causes of MI
(30). However, knowledge and awareness of the diagnosis are always fundamental for the
evaluation of patients.
Angiographic Findings in Acute Mesenteric Vein Thrombosis

Venous phase images during selective mesenteric arteriography are probably the best way to
demonstrate a venous thrombosis. Findings include a filling defect suggesting a thrombus within
the SMV, failure to demonstrate the SMV or portal vein, slow filling of the SMV, arterial spasm,
sluggish flow or failure of arterial arcades to empty, and prolonged blush in the involved bowel
segment. Angiography not only is useful for adequate diagnosis of acute mesenteric venous
thrombosis but also, due to the more indolent course of the disease, allows for intraarterial
therapy in some cases (Fig. 13-13). However, currently CT scans are utilized most frequently,
identifying mesenteric vein thrombosis in 90% of patients (30). Findings on CT suggestive of
mesenteric vein thrombosis include the presence of a thrombus, edematous changes of bowel
or mesentery, collateralization with enlarged spleen and the presence of ascites, and
asymmetric liver enhancement due to portal obstruction. Angiography and MR imaging are also
very good at detecting mesenteric vein thrombosis, with an almost 100% success rate. US,
being patient and operator dependent, is the least reliable, requiring validation with another
imaging technology such as CT (30).
Management of Mesenteric Venous Thrombosis

The goal of treating patients with mesenteric vein thrombosis is to minimize morbidity and
mortality with early diagnosis, early anticoagulation, and early interventionsurgical or
endovascular. The key to diagnosis is a high degree of clinical suspicion when evaluating
atypical abdominal pain and the liberal use of modern imaging methods. The introduction of
heparin therapy began the transition toward nonoperative management in the 1950s (30).
Anticoagulation should be continued indefinitely in the vast majority of cases, as it will decrease
recurrence from 30%-40% to 3%-5% (31,32). Coagulation status profiles should be assessed
before administration of heparin whenever possible (31). Considering that up to 69.6% of the
cases of mesenteric vein thrombosis are due to some type of hypercoagulable state, early
diagnosis of the underlying condition is highly desirable (30).
Operative intervention is necessary if peritonitis or worsening clinical status leading to sepsis is
present. Second-look operations are frequently necessary, as bowel viability is a major concern
(31). The 30-day mortality rate may be as high as 27%. Long-term survival of patients with
acute mesenteric venous thrombosis is significantly worse than that of patients with chronic
disease (36% vs 83% survival at 3 years) (32). There is evidence in the literature that patients
with acute mesenteric venous thrombosis who undergo anticoagulation, with or without surgery,
have improved survival compared to those who do not (32,33). Nonoperative management for
acute mesenteric venous thrombosis is possible with early diagnosis and when bowel infarction,
if present, has not led to transmural necrosis and bowel perforation. The morbidity, mortality,
and
survival rates in these cases are similar to those with surgical management (34).
FIGURE 13-13. A patient with abdominal pain and thrombophilia. A: CT of the abdomen
during the arterial phase shows premature enhancement of the right lobe of the liver by the
artery, due to occlusion of the right branch of the portal vein and a filling defect within the
right portal vein branch. The left branch is patent. B: Lower level of the CT scan shows the
thrombosed segment of the superior mesenteric vein. The SMA is patent. C: Late phase of
the SMA angiogram shows thrombosis within the superior mesenteric vein and in the right
branch of the portal vein. Note the asymmetry of the parenchymatous enhancement. In this
phase the left lobe is enhanced by the vein. Thrombolytic therapy with intraarterial
Retavase was performed. D: Late phase of the follow-up SMA angiogram showing
recanalization of the superior mesenteric vein and clearing of the hepatic portal perfusion.
The right portal vein remained occluded. Resolution of the symptoms resulted from the
treatment, and the patient was started on Coumadin.
Nonsurgical treatment of portal vein occlusion has been described by several authors.
Peripheral intravenous thrombolytic therapy with streptokinase to reopen portal vein occlusion
was used for the first time in 1971 by Paquet et al. (35). More recently the selective intra-
arterial infusion of thrombolytics, such as urokinase, have become more popular and have been
used successfully to reopen the portal vein or the SMV (36, 37, 38, 39). Percutaneous SMA
infusion of recombinant tissue plasminogen activator has also been used successfully to treat
SMV thrombosis (40). Experience gained from the available data shows that thrombolytic
therapy should be performed early in the hospital course, within 24 hours of the diagnosis (31).
A study of a relatively large series of patients published in 2005 by Hollingshead et al. regarding
transcatheter thrombolytic infusion for the management of acute mesenteric and portal vein
thrombosis showed total or partial resolution of the clot in 75% of cases and clinical
improvement of the symptoms in 85% of patients (36). The infusion was performed within the
portal venous system in some patients and transarterially in others. There was a 60% rate of
major
complications, including one death 2 weeks after the procedure (36). Although the available
literature is scanty and there are no prospective randomized studies comparing the use of
thrombolytics and heparin or surgery for the treatment of portal and mesenteric vein
thrombosis, there is a consensus that the symptomatic patients should be treated more
aggressively. Having in mind that a more aggressive treatment is necessary in some patients,
attempts to debulk the clot by thrombolytic therapy, balloon angioplasty (37,41), and stenting
have been made (42). Bilbao et al. offered a word of caution regarding percutaneous
treatment: while their patients clinically improved, morphologic results were only fair and partial
rethrombosis was observed. The limitations of percutaneous procedures in the recanalization of
acute portal vein thrombosis should be carefully assessed (41). Mechanical thrombectomy of
the portal vein with the Amplatz thrombectomy device was introduced in 1997 (43), and other
devices have also been used in the portal vein system (38) with success, using the transjugular
transhepatic approach (44) or a direct percutaneous approach, alone or in combination with
thrombolytic therapy (38,45,46). The main limitation of current thrombectomy devices is the
lack of efficacy in older, more organized clots, but mechanical thrombectomy in combination
with thrombolytic therapy offers a more rapid debulking of the clot, reducing the dose and time
of the thrombolytic drug use (46).
CHRONIC MESENTERIC ISCHEMIA

The concept of intestinal pain (mesenteric angina) from chronic arterial obstruction, analogous
to angina pectoris or calf claudication, is appealing in its simplicity and has been used since the
beginning of the 20th century. MI was first described by Antonio Hodgson in the latter part of
the 15th century, but it was only in 1895 that Elliot described a case of operative treatment of
necrotic bowel due to ischemia, which included resection and creation of stomas (47). In 1958,
Shaw and Maynard described the first thromboendarterectomy of the SMA for the treatment of
MI, with the subsequent development of other techniques such as vessel reimplantation and
aortovisceral arterial bypass with vein or prosthetic graft (28).
FIGURE 13-14. A: Occluded SMA and celiac trunk. Note the large inferior mesenteric
artery and wandering marginal artery. B: Collaterals through marginal artery (arrow) fill the
middle colic and pancreaticduodenal arteries, with filling of the SMA and celiac trunk. The
patient was severely symptomatic with mesenteric angina.
Chronic MI may be related to occlusion of only one or more of the splanchnic arteries.
However, occlusion of one, two, or three of the splanchnic arteries may or may not produce
symptoms (Fig. 13-14). Interestingly, there is little correlation between the degree of arterial
stenosis and clinical symptoms, probably because the abundant collateral circulation provides
some protection and the unstressed mesenteric circulation tends to be stable. The process is
chronic but may evolve to acute ischemia if there is acute occlusion or thrombosis of the
stenotic vessel. The connection between the SMA and the inferior mesenteric artery (IMA)
through the arc of Riolan is an important pathway to overcome chronic MI, and the direction of
the flow depends on the level and cause of obstruction (Figs. 13-1 and 13-14). The connection
of the SMA with the celiac trunk through the pancreaticoduodenal arcades is also an important
collateral communication between the two arterial symptoms and may in fact adequately supply
the mesenteric circulation without any perfusion deficits.
The most common cause of chronic MI is atherosclerotic disease at the origin of the SMA close
to the aortic wall, which determines a significant stenosis in the mesenteric artery (48). One or
more vessels may be involved. However, patients with occlusion of all three visceral arteries
may be completely asymptomatic. In addition to atherosclerosis, vasculitis and medial arcuate
ligament syndrome are other less common causes of chronic mesenteric angina. Typically,
chronic MI presents as recurrent abdominal pain, also called mesenteric angina. Mesenteric
angina is a clinical syndrome of reduced mesenteric flow that interferes with physiologic
function but does not cause infarction. In general patients present with periumbilical pain that
starts approximately 30 min. after eating and
lasts for 1 to 2 hours. Most patients recognize the relationship between eating and abdominal
pain. They may develop fear of eating due to the pain generated by digestion and peristalsis,
lose weight, and be malnourished as a result (48). Other situations of chronic MI are ischemic
colitis and focal ischemia of the small intestine, which may present with transitory symptoms of
abdominal pain that may worsen to complete gangrene.
Acute MI is frequently fatal, while progressive occlusion may be well tolerated for long periods
due to only mild or moderate deterioration of the intestinal function (malabsorption),
intermittency of symptomatology, and development of collateral circulation (Figs. 13-1 and 13-
14). Atheroma of the visceral arteries is a common finding, mainly confined to the aortic origin
of these vessels (Fig. 13-15), but more distal stenosis may be encountered (Fig. 13-16). One
third of the population over age 45 shows some narrowing of the celiac trunk and/or SMA,
which are affected in equal proportions (39). The IMA is less likely to be involved (Fig. 13-17).
Interestingly, the gross appearance of the bowel is unchanged regardless of the degree and
type of arterial lesions. Chronic MI usually presents with postprandial abdominal angina, which
is relieved by vasodilator drugs or fasting. It is frequently associated with food fear, weight
loss, and cardiovascular disease and, at the beginning, with constipation and, in the late stages,
with diarrhea secondary to malabsorption. Often, the patient's complaint may be misunderstood
as a neurotic complaint or even be confused with cancer of the stomach, pancreas, or liver.
FIGURE 13-15. The patient was a 70-year-old man with abdominal angina and weight
loss. A: Lateral view of the aortogram shows stenosis of the celiac and SMAs. B:
Selective angiogram of the celiac trunk shows severe stenosis of >80%. C: Lateral view of
the SMA angiogram shows critical stenosis of the proximal SMA: D: Lateral aortogram
showing patent SMA and celiac trunk following 6-mm balloon angioplasty from an axillary
approach. The symptoms resolved.
FIGURE 13-16. A: SMA angiography shows a focal stenosis in the midarea of the SMA,
beyond the origin of the inferior pancreatic artery, causing ischemia in the distal small
bowel and right colon. B: Balloon angioplasty with a 6-mm balloon was performed
successfully, with resolution of the mesenteric angina symptoms.
FIGURE 13-17. A: Lateral view of the abdominal aortogram shows occlusion of the celiac
trunk (open arrow), a proximal 95% stenosis of the SMA (closed arrow), and a 99%
stenosis of the IMA (arrowhead). Note the diffuse atherosclerotic disease in the aorta. B:
A right brachial artery approach was used for treatment. Balloon angioplasty was
performed with a 5-mm balloon. Postangioplasty aortogram shows patency of the SMA. C:
The inferior mesenteric artery (IMA) was treated with a 4-mm balloon. Postangioplasty
angiogram shows residual stenosis (arrow). D: A small Palmaz stent was placed in the
proximal IMA mounted on a 5-mm balloon.
Arcuate Ligament Compression Syndrome
Medial arcuate ligament syndrome (MALS) is a nonatherosclerotic narrowing of the celiac
trunk, which may or may not be related to recurrent mesenteric angina. There are questions
whether medial arcuate ligament syndrome is in fact a cause of mesenteric angina or
abdominal pain due to restriction of arterial mesenteric blood flow. Compression of the celiac
trunk by fibronervous structures and diaphragmatic muscle bands and ligaments is called celiac
or arcuate ligament compression (49). Harjola described clinical celiac trunk compression
syndrome in 1963 (50), including epigastric pain, weight loss, and external compression of the
celiac trunk, relieved by surgical release of the artery from the fibrotic celiac ganglion. The very
existence of the syndrome is still debated today. The two main reasons for debate are related
to the existence of potential abundant collateral among the visceral arteries and the fact that
about one third of people undergoing autopsy have a median arcuate ligament compression of
the celiac trunk. In addition, although the chronic compression of the celiac trunk may lead to
intimal hyperplasia and stenosis, with late development of atherosclerosis, in general one
stenotic vessel is less likely to cause symptoms of MI, particularly in the celiac trunk.
FIGURE 13-18. A: Lateral view of the abdominal aorta angiogram shows the patent celiac
trunk during inspiration. B: Lateral view of the abdominal aorta angiogram shows the
compression of the celiac trunk upon expiration, in a patient with medial arcuate ligament
syndrome.
Celiac compression syndrome has a low prevalence and no systematic studies have been
undertaken. The largest published series range from 31 to 51 patients (51,52), but in a series
of 152 lateral aortograms for various indications, 49% showed a celiac artery stenosis, but only
31% had Type I lesions (normal ostium with an asymmetric narrowing with inferior
displacement), and only 17 patients had abdominal pain. Similar rates of asymptomatic celiac
stenosis have been found in other angiographic series (53).
In patients with the true syndrome, female gender predominates, and the age range is from 30
to 50 years. In one third of patients, weight loss is the predominant complaint. There is often a
systolic epigastric bruit, altered by body position and respiration, and in general accentuated at
expiration.
Diagnostic aortography in lateral view, to observe the origin of the celiac and SMAs, is the most
reliable test (53). The typical picture is a smooth asymmetric narrowing of an external
compression and without arteriosclerosis in the ostium of the celiac trunk. In the majority of
patients, there is poststenotic dilation of the celiac trunk or evidence of collateral flow.
Provocation or accentuation of the findings is obtained by expiration during the angiographic
acquisition (Fig. 13-18). In a counterintuitive finding, there is relief of the stenosis during deep
inspiration, in the lateral view of the abdominal aortogram (Fig. 13-18) and worsening during
expiration. In more recent years, similar information can be obtained by CT angiography of the
abdominal aorta or carefully performed duplex US of the visceral arteries (49).
Treatment of celiac compression syndrome has traditionally been surgical, with relief of
constriction by division of the median arcuate ligament and/or fibrotic ganglion structures. Some
authors, however, do not believe in the existence of the syndrome and deny surgery (49). The
role of percutaneous angioplasty has not been determined, but it is likely to be unsuccessful
due to the firm elastic externa compression and recoil
(49). There is not enough experience reported in the literature regarding the treatment of this
syndrome with stenting.
Diagnosis and Therapy of Chronic Mesenteric Ischemia

The patient's management should start with a thorough investigation of risk factors for
atherosclerotic disease. A high degree of clinical suspicion and good history-taking skills are
important to narrow down the differential diagnosis. A diagnosis of cancer should be excluded.
Unless there is a sudden worsening of the patient's chronic symptoms, the angiogram may be
performed electively. Currently, noninvasive evaluation of the abdominal aorta and visceral
branches with CT angiography or MR angiography is preferred. If there is a high suspicious of
a significant stenosis, a selective visceral angiogram should be performed for definitive
diagnosis and immediate treatment. As always, the causative risk factors should be managed
to minimize disease progression.
FIGURE 13-19. A: SMA angiogram in a patient with mesenteric angina shows multiples
levels of stenosis due to fibromuscular dysplasia. Sixmillimeter balloon angioplasty was
performed with a polyvinyl chloride Gruntzig balloon. B: Angiogram post-balloon
angioplasty shows resolution of the stenosis. C: Six-month follow-up shows persistent
patency of the artery, but with a small aneurysm in the area of the previous stenosis.
Balloon angioplasty was used for the first time in 1980 to relieve recurrent abdominal angina in
a patient with fibromuscular dysplasia and stenosis in the SMA (Fig. 13-19) (54). In proximal
occlusions, balloon angioplasty followed by stent
placement (or simply primary stent placement) is the current best option (Fig. 13-20). Stent
technology has improved in the last few years, allowing for an increased role of the
endovascular treatment of SMA and celiac artery stenosis. Low-profile monorail systems with
balloon expanded stents are currently preferred for SMA ostial stenoses, allowing precise
placement of the stent with respect to the lumen of the aorta (39). Predilation is in general
necessary due to the difficulty in advancing the stent in the tight curve formed by the guide wire
coming from the femoral approach. Low-profile systems, with rapid exchange stent/catheters,
are advantageous in such cases, but the use of a guiding catheter or an introducer sheath is
necessary (Fig. 13-21). Modern balloon expandable stents are flexible and, in most cases,
follow the gentle curvature of the proximal SMA, and if the stenosis is long, a longer stent can
be used. Self-expandable stents can be used for SMA stenoses, particularly when the ostial
stenosis is hostile and a more flexible introducer system is necessary to cross the stenosis
(Fig. 13-22). Celiac artery stenosis is more rarely the cause of abdominal angina but may be
the culprit of hypoperfusion of the stomach, duodenum, and pancreas, if the collateral
circulation is not developed. There is less experience available in the literature about treatment
of celiac artery stenosis, but primary stenting is probably reasonable. It is necessary to have in
mind that the celiac artery is prone to external compression by the arcuate ligament of the
diaphragm (Fig. 13-23). Recurrent stenosis of the SMA after angioplasty is unfortunately
relatively frequent, and stenting may be indicated (Fig. 13-24).
FIGURE 13-20. A: Lateral view of the abdominal aortogram showing a relatively long
severe stenosis of the SMA, causing mesenteric angina. Balloon angioplasty, followed by
stenting, using a low-profile device, produced resolution of the SMA stenosis, as
demonstrated by this guiding catheter angiogram with the guide wire still within the artery.
B: Final lateral-view abdominal aortogram showing wide open SMA.
In chronic cases of MI, as in acute cases, the therapeutic strategy needs to be tailored to the
patient's clinical scenario. Seldom is it necessary to use mechanical thrombectomy and/or
papaverine infusion in the treatment, but more aggressive therapy for declotting may be
necessary if there is a sudden worsening of the patient's symptoms (thrombus on top of
atherosclerotic stenosis). For distal branch stenosis, expectant or surgical management is
probably the best options. Low-profile balloon angioplasty may be attempted in selected cases.
However, the more distal the stenosis, the higher the risk of complications.
Spontaneous or traumatic dissection of the proximal SMA is an unusual cause of MI. The
dissection usually originates near the ostium of the SMA, extending to the first branch, usually
the inferior pancreatic artery, in an anterior superior aspect. Two issues have to be taken in
consideration in these cases. First, the dissection may compress and collapse the true lumen of
the vessel, causing a significant stenosis in an otherwise normal vessel wall. Second, the
dissection may extend beyond the first branch, causing detachment of the proximal mesenteric
branches with occlusion, and as an aneurysm it may rupture into the peritoneal cavity.
Treatment of this condition is not always necessary, but the placement of a longer self-
expandable bare stent will recover the diameter of the SMA lumen (Fig. 13-25). However, a
bare stent will not resolve the problem of the dissection or close the communicating orifice. A
covered stent may be needed to accomplish this. Embolization of the false lumen of the
dissection with a microcoil is an alternative treatment (Fig. 13-26).
Comparative Results of the Treatment of Chronic Mesenteric

Ischemia
The optimal treatment for chronic MI, whether endovascular or open repair, remains
unresolved. One study from 2002 (55) reviewed a group of 47 patients, mostly females (70%)
treated
with aortomesenteric bypass, for chronic MI. The hospital mortality rate was 11%, with a mean
length of stay of 32 days, with relief of the abdominal pain in all patients and weight gain in 86%
at 31-month follow-up (27 months). Fourteen patients (34%) had diarrhea at discharge, which
persisted for more than 6 months in 10 of them. One patient had developed acute MI from a
failed graft (at 20 months), two patients had recurrent chronic MI following failed grafts (at 46
and 49 months), and one asymptomatic patient was found to have a failing graft with duplex US
scan (at 17 months); all grafts were revised. Primary, primary assisted, and secondary 5-year
graft patency rates with life-table analysis were 69% (standard error [SE], 17%), 94% (SE,
7%), and 100%, respectively, and the 5-year survival rate was 74% (SE, 12%). The results
showed good functional outcome and long-term graft patency for antegrade synthetic aortic-
mesenteric bypass for chronic MI (55).
FIGURE 13-21. A patient with mesenteric angina presented with acute lower GI bleeding.
A: SMA selective angiogram showed a very tight stenosis in the proximal SMA. Retrograde
filling of the hepatic circulation suggests proximal celiac artery obstruction. No bleeding
was identified at that time, but the catheter could not be advanced within the mesenteric
artery. B: A guiding catheter was used and a guide wire was inserted. An angiogram
showed a very tight stenosis. The angiogram shows the stenosis already partially dilated
with a 4-mm balloon. C: A balloon expandable stent was deployed. D: SMA angiogram
after stent placement shows patency of the artery. E: A full SMA angiogram was
performed and at this time a significant bleeding in the right colon was identified. F:
Superselective catheterization was performed with a microcatheter and embolization with a
single coil controlled the bleeding as demonstrated in this SMA angiogram.
However, percutaneous therapy for symptomatic visceral occlusive disease is rapidly gaining
popularity at many centers. A retrospective review of patients treated from January 1986 to
August 2003 was conducted by Landis et al. (56). Twenty-nine patients (mean age, 62 years)
were treated for clinical symptoms consistent with chronic mesenteric ischemia. Clinical
diagnosis was verified with angiographic assessment, and percutaneous transcatheter
angioplasty, with or without stent placement, was performed based on angiographic and/or
pressure gradient findings. A total of 63 interventions were performed in 29 patients during the
study period. Of these 63 interventions, 46 percutaneous transcatheter angioplasties and 17
stent implantation procedures were performed. Thirty-four interventions were performed for
SMA stenosis/occlusion, 17 interventions for celiac artery stenosis/occlusion, and 4
interventions on aortomesenteric graft stenoses. Technical success was 97%, and clinical
success (defined as clinical resolution of symptoms) was 90% (26 of 29 patients). Mean
duration of follow-up was 28.3 months. Primary patency for all interventions at 3, 6, and 12
months was 82.7% (95% confidence interval: 68.7-96.7), 78.9% (66.7-91.1), and 70.1% (55.1-
85.6), respectively. Primary assisted patency for all interventions at 3, 6, and 12 months was
87.9% (79.0-95.3), 87.9% (79.2-95.1), and 87.9% (77.3-98.3), respectively. An average of 1.9
interventions per patient was required. One major complication occurred (3.4%). There were
three minor complications (10.3%). Endovascular interventions for chronic MI were found to be
safe, with durable early and midterm clinical success. However, repeated intervention was often
required for improved primary assisted patency. In another publication Sharafuddin et al. (57)
evaluated the safety and assessed the role of endovascular therapy in a variety of conditions
related to celiac and mesenteric vascular occlusive disease. This retrospective study included
25 consecutive patients (mean age, 66 years), in whom 28 procedures were performed on 26
stenosed or occluded mesenteric vessels. Indications included chronic MI (21 patients),
including 2 patients who underwent stenting prior to a planned operative repair of an abdominal
aortic aneurysm close to the mesenteric orifice. Three liver transplantation patients underwent
stenting of an associated celiac artery stenosis. One patient with a splenorenal bypass
underwent stenting on an associated celiac artery stenosis. Follow-up parameters included
maintained patency on duplex sonography and sustained clinical benefit. The need for additional
interventions was also noted. Ninety-six percent of the procedures were technically successful.
Major complications occurred in three patients (one transient contrast-induced nephrotoxicity
and two pseudoaneurysms). Immediate clinical success was achieved in 22 patients (88%).
The three clinical failures included two patients with excellent angiographic outcome but with
single-vessel moderate severity disease. Survival-table analysis of delayed clinical outcome
showed primary and primary-assisted clinical benefits at 11 months of 85% and 91%,
respectively. Primary and primary-assisted stent patencies, as assessed by duplex sonography
and/or angiography, at 6 months were both 92%. Angiographically documented restenosis
occurred in three patients. Restenosis with celiac artery stents was due to extrinsic
compression in two patients, asymptomatic in one patient, and treated satisfactorily by
restenting in the other patients. Restenosis in one patient with an SMA stent was successfully
treated by restenting. The experience of the authors suggests a potential role for endovascular
therapy of celiac and mesenteric arterial occlusive disease in a variety of clinical scenarios, with
a low incidence of complications and a high technical success rate (57).
In another recent nonrandomized retrospective comparative study, a review of patients who
underwent endovascular or open mesenteric arterial revascularization for chronic MI between
January 1989 and September 2003 was performed (58). Indications for revascularization
included postprandial abdominal pain (92%) and weight loss (54%). All had atherosclerotic
visceral occlusive disease with a median of two vessels with more than 50% stenosis or
occlusion on angiography. Sixty patients (44 women; mean age, 66 years) underwent 67
interventions (43 vessels were bypassed, 23 vessels were treated with endarterectomies, and
22 vessels were treated with
angioplasty and stents). The median numbers of vessels revascularized were two in the open
group and one in the endovascular group. The 30-day mortality and cumulative survival at 3
years were similar (open, 15% and 62% 9%; endovascular, 21% and 63% 14%,
respectively; p = NS). Cumulative patencies at 6 months were 83% 7% and 68% 14% in
the open and endovascular groups, respectively (p = NS). Major morbidity, median
postoperative length of stay, and cumulative freedom from recurrent symptoms at 6 months
were significantly greater in the open group (open, 46%, 23 days, and 71% 7%, respectively;
endovascular, 19%, 1 day, and 34% 10%, respectively; p <0.01). The conclusion of the study
found endovascular revascularization as attractive because it carries equivalent patency to open
revascularization. However, the symptomatic benefit of endovascular revascularization was not
as good, probably as a result of incomplete revascularization. Despite incomplete
revascularization, endovascular therapy showed equivalent survival and lower morbidity
compared with open revascularization, suggesting that endovascular revascularization needs
further evaluation to determine if it is superior to open revascularization (58). Another
publication, with an extensive review of the literature and a meta-analysis of the data, showed
mesenteric angioplasty and stenting to have a technical success rate of 80% to 100% and a
clinical efficacy of 80% to 95%. Some published studies indicate a primary patency of 75% to
85% (59).
FIGURE 13-22. Female patient with severe abdominal pain evolving from mesenteric
angina present for at least 2 years. A: Abdominal aortogram shows a prominent marginal
artery and faint opacification of the SMA: B: Lateral view of the abdominal aortogram
shows total occlusion of the origin of the SMA. A guide wire was advanced into the SMA,
and progressive dilation with a 4-mm balloon and eventually a 6-mm balloon was used.
Calcification was noted in the wall plaque. C: SMA angiogram postangioplasty shows
significant recoil of the stenosis. Due to the length of the stenosis and the curvature of the
vessel, a Wallstent was selected to treat this patient's stenosis. D: Lateral abdominal
aortogram was performed and showed a patent SMA after stenting. Note the stent
protruding within the aorta, one of the problems when placing a self-expanding in such a
vessel; a balloon expandable stent allows for more precise placement. Note the stenosis of
the celiac artery. E: AP view of the abdominal aortogram shows patency of the SMA with
perfusion of the mesenteric circulation.
FIGURE 13-23. Patient with abdominal angina. A: Lateral view of the abdominal aortogram
shows the celiac trunk to be occluded. B: Selective injection of the celiac trunk through a
guiding catheter shows the very narrow stenosis at the ostium of the celiac. The wire is
already within the hepatic artery. C, D, E: Placement of the balloon expandable stent is
shown. F: Final lateral abdominal aortogram shows a wide patent celiac trunk after
stenting.
FIGURE 13-24. A: Lateral-view abdominal aortogram shows a recurrent excentric stenosis

of the SMA, 2 years after balloon angioplasty. B: Poststenting angiogram shows patency
of the SMA. Note that there is some degree of underdilation of the artery. There was total
resolution of the symptoms for more than 10 years.
FIGURE 13-25. A patient with abdominal trauma developed dissection of the SMA,
accompanied by abdominal pain after eating and significant dilation of the stomach. A: CT
in axial view of the abdomen shows the dissection and the dilated stomach. B: Coronal
view of the abdomen shows the dissection of the SMA. Note the compression of the SMV.
C: Lateral view of the SMA angiogram shows the dissection in the proximal SMA and
stenosis of the true lumen. D: Poststenting angiogram shows a wide arterial true lumen.
The stent was an EV3 Nitinol stent 6 mm in diameter. Note the filling of the middle colic
artery from the false lumen. The bare stent does not close the leak into the dissection.
FIGURE 13-26. A patient with spontaneous dissection of the SMA causing abdominal pain.
A: Ultrasonography of the SMA shows the true lumen and the dissection false lumen. B:
The treatment was performed with stenting of the true lumen with a self-expandable Nitinol
stent and embolization of the false lumen with detachable coils. Note the filling of the
middle colic artery through distal collaterals.
ISCHEMIC COLITIS
Ischemic colitis is probably one of the most common forms of MI, responsible for almost 50%
of the overall cases with a MI diagnosis. A variety of names is found in the literature including
necrotizing colitis, pseudomembranous colitis, ulcerative colitis, and gangrenous colitis.
Ischemic colitis syndrome is usually in the left side of the colon and results from a reduction in
blood flow (Fig. 13-27). The critical point is often the splenic flexure (Griffiths' point), where
collateral circulation between the SMA and the marginal artery branch of the inferior mesenteric
artery supplying the descending colon merge. Griffiths' point is defined as the site of (a)
communication of the ascending left colic artery with the marginal artery of Drummond and (b)
anastomotic bridging between the right and the left terminal branches of the ascending left colic
artery at the splenic flexure of the colon. Analysis of arteriographic studies shows that
anastomosis at Griffiths' point is present in 48% of cases, poor or tenuous in 9%, and absent in
43% of cases (60). This critical point is of significance in occlusive vascular impairment of the
left colon, both in spontaneous instances and following surgical ligation of the inferior
mesenteric artery and in nonocclusive ischemic colitis. Its relationship to arteriosclerotic
stenoses and low-flow states has been described (60). Individuals with absence of dependable
anastomoses at Griffiths' point at the splenic flexure may be particularly vulnerable to low
perfusion states and develop the syndrome of
ischemic colitis. Complete arteriographic evaluation is necessary in ischemia of the colon. This
includes particularly assessment of atherosclerotic changes at or near the ostia of the major
visceral arteries and the vascular arrangement at Griffiths' point. Ischemic colitis, however, is in
general a focal small vessel disease, which may be aggravated by low-flow states. The most
common causes of ischemic colitis are spontaneous thrombosis of colonic vessels, vasculitis,
venous occlusion, and increased intraluminal pressure (due to colon cancer or obstruction).
Other contributors are hypercoagulable states, sickle cell disease, drugs such as oral
contraceptives, and illicit drugs (61).
FIGURE 13-27. Schematic drawing of the colon showing the location and frequencies of
ischemic colitis in 1,024 patients. Note the much higher incidence in the left colon and
sigmoid.
FIGURE 13-28. Barium enema in a patient with ischemic colitis. Note the thickening of the
bowel walls and thumbprinting, characteristic of ischemic colitis.
The presentation of ischemic colitis includes reversible ischemia with submucosal and intramural
hemorrhage, transient colitis, stricture formation, and fulminant colitis. The left colon is affected
in 75% of cases. Ischemic colitis is more common in the descending colon (27%), sigmoid
(23%), and splenic flexure (23%). The rectum is the site for only 4% of IC (Fig. 13-27) (62).
The most common radiographic findings are thumbprinting (mucosal edema), which is an early
finding (Fig. 13-28) and may disappear within 48 hours to several weeks, mucosal irregularity,
ulcerations (more advanced vascular insult), tubular narrowing (nonreversible change), and
funneling (Fig. 13-29). Ischemic colitis can be spontaneously reversible (63).
Clinical presentation may include red or maroon blood mixed with soft or liquid stool and mild,
crampy, left-sided abdominal pain of acute onset. Diarrhea, nausea, vomiting, and anorexia are
frequently seen. Constipation may result from a stricture secondary to fibrosis at a later phase
(63). Currently, endoscopy is the preferred test for the diagnosis of ischemic colitis and shows
segmental lesions, sharp demarcation between injured and normal mucosa, usually sparing the
rectum (Fig. 13-30). Biopsies reveal inflammation resembling ulcerative colitis or Crohn's
disease. Barium enema may show the thumbprinting, but is nonspecific. CT scan shows
thickening of the mucosa and may exclude other lesions, such as colon cancer. However, colon
cancer may be associated with the development of ischemic colitis, and the diagnosis of
ischemic colitis may be missed by imaging in the presence of a significant cancerous lesion
(64). In a retrospective study of 170 patients with ischemic colitis, 8 patients were found to
have partially obstructive carcinoma of the colon, located distal to the ischemic point, 7 in the
sigmoid and 1 in the splenic flexure. The frequency of this association, 5.3%, necessitates
careful examination by radiologists and surgeons. The radiologist and the endoscopist should
be alert to the association of ischemic damage proximal to an obstructive colorectal cancer.
The surgeon must examine any colonic segment removed for carcinoma to exclude an ischemic
process in the area of the anastomosis and prevent leakage at the anastomosis or stricture
formation (64).
Mesenteric angiography is probably not indicated in most cases but, when performed, may
demonstrate increased colonic wall thickening, vascular obstruction or marked hypovascularity
with or without submucosal shunting, and absence or reduced circulation at Griffiths' point.
Therapy is mostly supportive, with fluid resuscitation and bowel rest. Improvement is seen
within 24 to 48 hours of symptom onset in most patients. Indications for surgical exploration
include peritonitis, massive bleeding, and clinical deterioration. Colonic stenosis may cause
partial or complete obstruction of the bowel, and partial colon resection may be necessary.
FOCAL ISCHEMIA OF THE SMALL INTESTINE

Focal ischemic disease of the small intestine may progress to inflammation, ulceration, and
stenosis. The most common causes are strangulation (hernia), trauma to the abdominal wall,
inflammatory vessel disease, radiation injury (enteritis), induction by drugs, and acute occlusive
ischemia (SMA) in large vessel disease (SMA occlusion) or in small vessel disease (embolism-
vasculitis) (Fig. 13-31).
Vasculitis
Various forms of vasculitis may result in MI, ischemic colitis, or aneurysm formation in the aorta
or intestinal blood vessels. Vasculitides may involve large- and/or medium-sized vessels,
medium- and/or small-sized vessels, or small-sized vessels only. It is essential to differentiate
between the different forms of vasculitis since diagnostic tests and therapies differ greatly.
Gastrointestinal manifestations of vasculitis can generally be detected using catheter
angiography and/or MR angiography. Various laboratory tests are helpful in establishing the
diagnosis in patients in whom vasculitis is clinically suspected. In addition, the diagnosis should
be confirmed using histology or angiography if possible. Treatment of vasculitis not caused by
chronic infection consists of high-dose corticosteroids and, in the case of polyarteritis nodosa or
vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs), cyclophosphamide
(65).
Intestinal vasculitis is a rare cause of MI. It results in chronic arterial insufficiency in most
cases, sometimes in acute MI. Abdominal symptoms like pain and cramps, postprandial
intestinal angina, diarrhea, anorexia, and perforation are nonspecific and do not allow for
differentiation between vasculitic and noninflammatory causes of MI. Conventional radiographic
studies and endoscopy may not confirm the underlying process either. Therefore, extraintestinal
symptoms of vasculitis must be observed carefully to diagnose a systemic vasculitis with
potential involvement of intestinal arteries. Extraintestinal manifestations are multifaceted
including malaise, rheumatic symptoms, and more specific findings like cutaneous
efflorescences and organ-specific vasculitic damage due to ischemia of inner organs, nerves,
and sensory organs. While some vasculitic disorders are characterized by specific laboratory
markers (ANCAs and anti-double-stranded DNA antibodies), others appear with less specific
signs (66). Prior to treatment, the diagnosis should be established by biopsy of suspected
tissue and subsequent histologic analysis. Angiography can be helpful in diagnosis of
syndromes involving medium-sized or larger vessels. The treatment of choice is glucocorticoids,
while in patients with extensive visceral, especially renal, involvement, cyclophosphamide should
be added. When glucocorticoids cannot be tapered or the disease cannot be controlled, other
immunosuppressive agents should be employed. In difficult diagnostic situations, with mere
suspicion of vasculitis, glucocorticoids may prove effective (67).
FIGURE 13-29. A: Barium enema in a patient with ischemic colitis. B: Inferior mesenteric
artery angiogram showing patent arteries but very little or no perfusion of the left colon
wall. C: Late phase of the angiogram shows venous return, suggesting submucosal
shunting but without significant enhancement of the bowel wall. This aspect is not
characteristic of ischemic colitis.
FIGURE 13-30. A: Inferior mesenteric artery angiogram showing significant
hypervascularity of the left colon walls, with wall enhancement. B: The late phase shows a
robust venous return with dense filling of the left colic veins, suggesting submucosal
shunting. C, D: Colonoscopy showed mucosal thickening, redness, and shallow ulcerations,
consistent with colonic ischemia, despite the suggested hypervascularity shown in A and B.
Classification of Vasculitides Involving the Gastrointestinal

Tract
The vasculitides comprise a diverse group of conditions characterized by inflammation and
necrosis of vessel walls. They have many causes and pathogenetic mechanisms, although
these are not completely understood. Furthermore, marked variability
in clinical manifestation has prevented development of a universally accepted classification of
vasculitis. Several investigators have attempted to classify vasculitis on the basis of differing
aspects of the disease such as extent or location of involvement, pathologic characteristics,
pathogenetic processes, or clinical symptoms (68, 69, 70, 71). In 1990, the American College
of Rheumatology published an approach to classifying vasculitides for clinical trials in an
attempt to establish the clinical findings that are helpful in identifying vasculitis and distinguishing
it from other diseases (69). However, this study was limited to seven forms of vasculitis that
are usually considered to be clinically distinct: polyarteritis nodosa, Churg-Strauss syndrome,
Wegener granulomatosis, hypersensitivity vasculitis, Henoch-Schnlein syndrome, giant cell
(temporal) arteritis, and Takayasu arteritis. In 1994, the Chapel Hill International Consensus
Conference proposed names and definitions for selected categories of vasculitis (68). The
authors classified 10 selected vasculitides as large-vessel vasculitis, medium-sized vessel
vasculitis, and small-vessel vasculitis, depending on the type of vessel that is predominantly
affected. Large-vessel vasculitis affects the aorta and the largest arterial branches directed
toward major body regions, medium-sized vessel vasculitis affects the main visceral arteries
and their branches, and small-vessel vasculitis affects arterioles, venules, and capillaries.
Although there remains substantial overlap among the different vasculitides, this classification
system helps establish the concept of small-vessel vasculitides as distinct from vasculitides
that predominantly affect medium-sized and large arteries (72). However, this classification
system assigns microscopic polyangiitis too prominent a place in the family of vasculitides, and
other clinical, biologic, and histologic criteria are not taken into consideration. The ability to
identify pathogenic antibodies in tissue and serum led to discoveries that allowed the
categorization of certain small-vessel vasculitides. Recently identified ANCAs are closely
associated with three major categories of small-vessel vasculitis with absence or paucity of
vascular immune deposits, such as Wegener granulomatosis, microscopic polyangiitis
(polyarteritis), and Churg-Strauss syndrome (73). However, assays for ANCA are negative in
approximately 10% of patients with typical Wegener granulomatosis or microscopic polyangiitis,
and the specificity of a positive ANCA assay is not absolute. Immune complexes are identified
in certain types of vasculitis, including Henoch-Schnlein purpura, lupus vasculitis, Behet
disease, and others (Fig. 13-32) (73,74).
FIGURE 13-31. A patient with nonspecific vasculitis of the small bowel. A: Late phase of
SMA angiogram showing abnormal vessels within the wall of a segment of small bowel.
Note the thickening of the bowel wall. B: Barium follow-through of the small bowel shows
edema of the small bowel mucosa and disruption of the mucosal pattern, as well as
reduced motility. C: Histology of the bowel wall shows lymphocytic infiltrate and arterial
occlusion. (See the color insert.)
FIGURE 13-32. A patient with vasculitis of the small bowel. A: Arteriogram of the SMA
showing hypervascularity and abnormal small arteries at the distal jejunum/ileum. No A-V
shunting was observed. B: Barium follow-through showed small bowel wall thickening and
disruption of the mucosal pattern. C: Histology shows edema of the mucosa and
submucosa with lymphocytic infiltrate and vascular wall thickening, consistent with
vasculitis. (See the color insert.)
Middle - Left Colic Artery Syndrome

Middle colic-left colic artery syndrome is a variant of periarteritis nodosa. It is characterized by
necrosis of the vessel wall producing aneurysmal changes associated with areas of intramural
dissection, giving a very characteristic nodularity and beaded appearance. It can lead to intra-
abdominal and or retroperitoneal hemorrhage, mesenteric infarction, and, occasionally,
intestinal perforation (Fig. 13-33). Differential diagnosis should include Strongyloides stercoralis
hyperinfection, which may cause involvement of the small bowel or large bowel, presenting with
wall thickening and ulcerations. The angiogram shows long-segment dilation of the left colic
artery in addition to sausage link appearance in SMA branches (75).
ANCA-positive vasculitides are a heterogeneous group of disorders. They can be disabling
multi-organ system conditions. Involvement of small and occasionally medium-sized blood
vessels is generally the rule. Recent classification changes and advances in laboratory testing
have made it easier to work up a patient suspected of having an ANCA-associated vasculitis.
Syndromes can at times overlap, leaving a class of patient that does not fit into one specific
group. Patients frequently present with a myriad of symptoms, ranging from sore throat, fever,
arthralgias and myalgias, to overt hemorrhage and/or renal failure (66).
CONCLUSION
The diagnosis of MI, chronic or acute, requires a high degree of clinical suspicion, early
diagnosis, and early intervention, and the treatment in general is varied. Mortality remains high
despite the recent advances in treatments. Nevertheless, there has been an improvement of
mortality rates when early treatment is applied. An important observation is that intestinal
ischemia may be equally related to vascular occlusion and low-flow situations.
Alternative treatments include intra-arterial infusion of vasodilators, thrombolytic therapy,
mechanical thrombectomy, balloon angioplasty, stent placement, and surgical repair or bowel
resection. Correction of systemic factors contributing to the perpetuation of the ischemic
phenomena is paramount to treatment success.
FIGURE 13-33. Middle colic-left colic artery syndrome, a variant of periarteritis nodosa,
with necrosis of the wall of the vessel. A: The process produces aneurysmal dilatation of
the colonic arteries associated with areas of intramural dissection, giving a very
characteristic nodularity and beaded appearance (arrows). B: The late phase shows a
large draining vein. C: The specimen of the diseased segment of bowel shows a large
aneurysm with intraparietal bleeding. (Courtesy of Dr. Juan Oleaga.) (See the color insert.)
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 14 - Acute Gastrointestinal
Bleeding
Chapter 14
Acute Gastrointestinal Bleeding
David Phillips
Bleeding from the gastrointestinal tract is a common and serious clinical problem. Acute,
massive upper gastrointestinal bleeding has an incidence of 40 to 150 episodes per 100,000
persons annually, with a mortality rate of 6% to 10% (1, 2, 3, 4). Acute, massive lower
gastrointestinal bleeding has an incidence of 20 to 27 episodes per 100,000 persons annually,
with a mortality rate of 4% to 10% (5,6). Mortality rates increase in patients with advancing age
and increasing number of associated underlying comorbidities, specifically renal and hepatic
dysfunction, heart disease, and malignancies (2, 3, 4,7).
Gastrointestinal bleeding can present in several forms depending on the rate of blood loss:
microscopic blood loss presents as iron-deficiency anemia or hemoccult-positive stools;
macroscopic blood loss may result in vomiting of bright red blood (hematemesis) or vomiting of
altered dark blood (coffee-ground emesis); and passing of black tarry stools (melena) or
passing of bright red blood via the rectum (hematochezia). Hematochezia usually results from a
lower gastrointestinal tract bleed but sometimes will occur from a briskly bleeding upper
gastrointestinal source (1,8). Most cases of gastrointestinal bleeding resolve spontaneously,
regardless of the amount of blood lost (9, 10, 11).
This chapter discusses major bleeding (loss of >2 units of blood) in the upper and lower
gastrointestinal tract from the four major sources cited above and emphasizes evidence-based
treatment.
INITIAL CLINICAL MANAGEMENT

Initial assessment includes a pertinent history and physical examination, and laboratory testing
including hemoglobin, hematocrit, coagulation status, liver function tests, serum electrolytes,
BUN, and creatinine. Hemoglobin <10 g/100 mL is associated with an increased risk for
morbidity and mortality. Blood should be sent for type and cross-matching for transfusion.
Rapid restoration of intravascular volume should be carried out based on estimated blood
volume loss. Patients in shock with hypotension (systolic blood pressure <90 mm Hg lying
down), tachycardia, and cold extremities may have a deficit of at least 40% of the blood
volume. Patients with less severe but substantial blood loss (20%-40%) show hypotension in
the upright position. Orthostatic vital signs should be checked in all patients not in shock by
sitting the patient up with legs dangling for 5 minutes. An elevation in pulse of >20 beats/minute
or a fall in blood pressure of >10 mm Hg is a positive sign, indicative of at least a 20% blood
volume loss. Signs of peripheral hypoperfusion, such as clammy, cool, pale extremities, reflect
a volume loss of at least 20%. These signs are less reliable in the elderly, who may show
exaggerated postural changes or blunted changes in heart rate, when using -blocker
medication. Patients showing a volume deficit of >20% of the blood volume require prompt and
aggressive resuscitation (12). Good venous access to allow rapid intravenous therapy is
critical. The elderly and patients with comorbidities such as carotid, coronary, renal, hepatic, or
pulmonary insufficiency require central venous or pulmonary artery catheter placement for
monitoring. Urine output should be monitored after placing a Foley catheter. Coagulation
defects should be corrected with component therapy or fresh-frozen plasma.
ACUTE UPPER GASTROINTESTINAL BLEEDING

Upper gastrointestinal bleeding is defined anatomically as a bleeding source proximal to the
ligament of Treitz. Acute upper gastrointestinal bleeding accounts for ~85% of hospital
admissions for gastrointestinal bleeding and is a common and potentially deadly condition (12).
Clinical Presentation
Hematemesis and melena are common clinical signs in acute upper gastrointestinal bleeding.
Patients with massive hematemesis and mental obtundation should undergo endotracheal
intubation to protect the airway. Massive acute upper gastrointestinal bleeding may present
with hematochezia. Passage of a nasogastric tube is required to interrogate for the presence of
blood in the stomach even in instances where lower gastrointestinal bleeding is suspected. A
negative gastric aspirate revealing bilious material to assure absence of bleeding within the
duodenum below the pyloric valve. All sources of gastrointestinal bleeding have high associated
morbidities; upper gastrointestinal bleeding has the highest risk for life-threatening bleeding (1).
The mortality rate for patients with major gastrointestinal bleeding, especially upper
gastrointestinal bleeding related to peptic ulceration, has remained unchanged at 5% to 12%
despite general improvements in management (12).
Endoscopy is the procedures of choice for identifying and treating the source of acute upper
gastrointestinal bleeding. The complication rate for endoscopy during acute upper
gastrointestinal bleeding is 0.9%. Most complications are cardiopulmonary in nature. Aspiration
and arterial oxygen desaturation may occur.
Etiology
Gastroduodenal peptic ulcer disease is the most common cause of acute upper gastrointestinal
bleeding, accounting for half of bleeding episodes. Bleeding from esophageal and gastric
varices secondary to portal hypertension is the next most frequent source, identified in 10% to
20% of patients (2). Fifteen to thirty percent of patients with acute upper gastrointestinal
bleeding have mucosal lesions, broadly characterized as gastritis or duodenitis (1). Mallory-
Weiss mucosal tears at the gastroesophageal junction account for 8% to 10% of acute upper
gastrointestinal bleeding. Esophagitis (3% to 5%), malignancy (3%), Dieulafoy's lesion (1% to
3%), and watermelon stomach (1% to 2%) are the remaining lesions likely to be the source of
acute upper gastrointestinal bleeding.
GASTRODUODENAL PEPTIC ULCER BLEEDING
Pathogenesis
The pathogenesis of bleeding peptic gastric and duodenal ulcers has not been clearly
elucidated. In a review of bleeding peptic ulcer, Laine and Peterson cited a histological finding in
surgically resected gastric ulcers associated with bleeding; the resected specimens revealed
an artery eroded by the crater of the ulcer (13). In most cases the diameter of the bleeding
artery is small (mean, 0.7 mm; range, 0.1 to 1.8 mm) (14). A larger arterial size is thought likely
to be associated with increased morbidity and mortality, as well as a decreased likelihood of
success with endoscopic therapy (15). A retrospective review noted that arterial diameter
ranged from 1.5 to 3.4 mm in approximately a quarter of patients with fatal bleeding ulcers
(16).
High levels of acid secretion do not appear to account for the development of bleeding in
patients with peptic ulcers. Basal and stimulated acid output as well as sensitivity of parietal
cells to pentagastrin, is similar in patients with bleeding duodenal ulcers and in those with
nonbleeding ulcers (17,18).
The presence of Helicobacter pylori in patients with bleeding ulcers may be 15% to 20% lower
than in patients with nonbleeding ulcers (19, 20, 21). A number of large case-control and cohort
studies suggest that the risk of upper gastrointestinal bleeding is higher for patients who use
nonsteroidal anti-inflammatory drugs (NSAIDs) than for those who do not (22, 23, 24, 25, 26,
27, 28). A meta-analysis found that age >60 years, a prior gastrointestinal event, and use of
NSAIDs for <1 month were associated with higher risks of complications (29).
Ingestion of NSAIDs may cause both gastric and duodenal ulcers. Gastric ulcers are more
common than duodenal ulcers; however, the increased rates of complications associated with
use of NSAIDs are similar for the two forms of ulcer (22, 23, 24).
Steroids have been reported to double the NSAIDassociated risk of serious gastrointestinal
complications (29). The concomitant use of steroids and NSAIDs may be associated with a 10-
fold increase in the risk of upper gastrointestinal bleeding (30).
Twenty percent of patients who have bleeding ulcers present with melena, 30% with
hematemesis, and 50% with both (31). Hematochezia occurs with bleeding ulcers in as many
as 5% of patients (31,32). Failure of the gastric aspirate to clear with lavage, bleeding
manifested as repeated red hematemesis or hematochezia, and hemodynamic instability on
presentation are the clinical markers that indicate severe bleeding or high risk for more bleeding
(31,33). Advanced age and the presence of serious underlying medical illness are important in
predicting survival after an acute episode of bleeding (33, 34, 35). Patients >60 years of age
with bleeding peptic ulcers have been reported to have a mortality rate of 10%, compared to
0.5% in those 60 years (35).
Clinical Management
First steps in managing acute peptic ulcer bleeding include hemodynamic assessments and,
when needed, resuscitative measures.
Endoscopic Therapy
Upper endoscopy is the primary tool for diagnosing and treating most upper gastrointestinal
bleeding. The endoscopic features of an ulcer are helpful in predicting prognosis regarding
rebleeding. A flat pigmented spot has been reported to have a 10% likelihood of further
bleeding; an adherent clot, a 22% likelihood of further bleeding; a visible vessel, a 43%
likelihood of further bleeding; and active bleeding, a 55% likelihood of further bleeding when
there is no intervention (13). Ulcers >1 or 2 cm in diameter have increased rates of rebleeding
and death after endoscopic hemostatic therapy (31,35,36). Large ulcers are more likely to have
features of recent bleeding than are small ulcers (35).
Endoscopic methods to control acute bleeding peptic ulcer include lasers, heater probes,
electrocoagulation, and ulcer injection. Laser therapy to control acute bleeding peptic ulcer,
although effective, may cause transmural injury and requires advanced technical skills.
Presently laser therapy is not the recommended treatment of choice for bleeding ulcers.
Bipolar electrocoagulation and heater-probe therapy use thermal contact to cause hemostasis.
Both require a portable generator as well as a probe, which is passed through the biopsy
channel of the endoscope and placed firmly on the bleeding lesion. Heat generated by electrical
energy (bipolar electrocoagulation) or thermal energy (heater probe) leads to coagulation and
hemostasis. Temperatures as high as 100C (bipolar electrocoagulation) and 250C (heater
probe) have been reported (37,38). Injection therapy is a nonthermal method of achieving
hemostasis. One of a variety of solutions is injected into the base of the ulcer with a catheter
that has a retractable needle (similar to the catheter used for esophageal variceal
sclerotherapy). Solutions documented in controlled trials to provide effective hemostasis include
absolute ethanol, epinephrine (at a dilution of 1:10,000), polidocanol (a sclerosing agent usually
injected immediately after the injection of epinephrine), and even normal saline. Many suggest
that local compression of the blood vessel by the injected solution results in hemostasis and the
results from normal saline injections support the theory (39,40).
Failure to control acute bleeding peptic ulcer with endoscopic therapy necessitates other
interventions. Slightly more than 10% of patients require urgent surgery for bleeding despite
endoscopic therapy (13).
Arteriography and selective arterial embolization or vasoconstrictor infusion is reserved for
endoscopic failures and patients deemed poor surgical risks. Experimental studies have shown
that a bleeding rate as low as 0.5 mL/minute may be detected by arteriography (41). In the
event of endoscopically uncontrollable bleeding from gastroduodenal ulcers, selective
embolization of the feeding artery is the procedure of choice for most interventional radiologists
(Fig. 14-1A and B). Bleeding from peptic duodenal ulcer requires selective arteriography of the
gastroduodenal and inferior pancreatoduodenal arteries. Because of dual blood supply through
collaterals both arteries may require selective embolization to control bleeding (Fig. 14-1C and
D). Because of the dual blood supply selective intra-arterial vasopressin infusion is usually not
attempted to control bleeding peptic duodenal ulcer. Bleeding peptic gastric ulcers require
selective left gastric arteriography and embolization (Fig. 14-2). Metallic coils or Gelfoam
pledgets are
the most popular embolic agents used. Because of the copious blood supply to the duodenum
and stomach the risk of infarction after selective left gastric artery (LGA), embolization is very
low. The LGA can generally be embolized with impunity even if angiographic extravasation is
not seen, as long as it is highly suspected of being the source of bleeding. On the other hand,
the gastroduodenal artery should be embolized if there is documented angiographic or
endoscopic evidence of bleeding. Selective left gastric artery vasopressin infusion is usually
reserved for uncontrollable bleeding gastritis (Fig. 14-3). Selective intra-arterial vasopressin
infusion to control gastrointestinal bleeding is usually begun at 0.2 unit/minute. Twenty minutes
later an arteriogram is performed to assess bleeding control. If the bleeding stops the infusion
is continued for 24 hours and tapered by 0.05 unit/minute in the next 24 hr. Up to 0.4 unit/minute
of intra-arterial vasopressin infusion may safely be used if 0.2 unit/minute fails to control
bleeding. During intra-arterial vasopressin infusion it is imperative that the patient is monitored
for signs of cardiac arrhythmias or peripheral ischemia.
FIGURE 14-1. A 66-year-old male bleeding from a duodenal ulcer. A: Selective

gastroduodenal artery (GDA) arteriogram reveals bleeding from pancreatic arcade branch
(arrow). B: GDA embolized with microcoils. C: Inferior pancreatic artery (IPA; arrow)
branch also supplying bleeding site. D: IPA branch embolized with microcoils.
ACUTE ESOPHAGEAL AND GASTRIC VARICEAL BLEEDING
Etiology/Pathogenesis
Most often bleeding occurs from esophagogastric varices secondary to portal hypertension,
with cirrhosis being the underlying pathology. Varices in the distal esophagus and proximal
stomach are a component of the collateral network that diverts high-pressure portal venous
flow through the left and right gastric veins and the short gastric veins to the azygous system.
Less commonly, varices develop at other sites in the gastrointestinal tract but are less prone to
rupture in those locations. Esophagogastric varices do not bleed until the portal pressure
exceeds 12 mm Hg, and then they bleed in only one third to one half of patients (42). The
pathogenesis of variceal rupture is not completely understood but is most likely multifactorial
(43).
A hypothesis of variceal rupture based on Laplace's law was described by Polio and Groszman
(44). They observed that
variceal size, magnitude of portal pressure, and thickness of the epithelium overlying the varix
all significantly separate bleeders from nonbleeders. Laplace's law states that variceal wall
tension is directly related to transmural pressure and varix radius and inversely related to
variceal wall thickness, thus combining all three of these variables. All of these parameters
cannot be measured clinically, therefore there are inherent inaccuracies in predicting which
patients with varices may bleed. Three variables predictive of variceal bleeding are Child-Pugh
class, variceal size, and presence and severity of red wale markings (indicative of epithelial
thickness) (45).
FIGURE 14-2. A 74-year-old male bleeding from a gastric ulcer. A: Selective left gastric
artery (LGA) arteriogram. B: Bleeding (arrow) is noted along the greater curvature of the
stomach in the late arterial phase. C: Bleeding stopped with selective proximal LGA
embolization with microcoils.
Bleeding from esophagogastric varices accounts for one third of all deaths of patients with
cirrhosis. Overall, acute variceal bleeding is associated with a mortality rate of about 25% to
30%. Approximately one half of deaths are due to uncontrolled bleeding. The risk for death
from bleeding is mainly related to the underlying hepatic functional reserve. Patients with
extrahepatic portal venous obstruction and normal hepatic function rarely die of bleeding
varices, whereas those with decompensated cirrhosis (Child-Pugh class C) may face a
mortality rate >50%. The greatest risk for rebleeding from varices is within the first few days
after the onset of bleeding; the risk declines rapidly between then and 6 weeks after
hemorrhage onset, when it returns to the prebleeding risk level. These patients are often very ill
and display hepatomegaly, splenomegaly, ascites, encephalopathy, asterixis, and other system
failures. Blood studies may show anemia, leukopenia, thrombocytopenia, elevated prothrombin
time, elevated INR, hypoalbuminemia, elevated aspartate aminotransferase, elevated alanine
aminotransferase, elevated alkaline phosphatase, elevated glutamyl transpeptidase, and
elevated total bilirubin. Patients may have positive serology for hepatitis A, B, and C.
Hyponatremia, hypokalemia, and metabolic alkalosis are common electrolyte abnormalities.
FIGURE 14-3. Poor-surgical-risk patient with bleeding gastritis unresponsive to endoscopic

therapy. A: Selective left gastric artery (LGA) arteriogram revealed a focal bleeding site
(arrow) and numerous feeding arteries. B: Patient was started on intra-arterial vasopressin
infusion into the LGA at 0.2 unit/minute, with control of bleeding over a 24-hour period.
Vasopressin infusion dose was tapered over the next 24 hours and then discontinued. Note
spasm of feeding vessels.
Diagnosis
Endoscopy to identify and confirm esophageal and gastric varices as the source of bleeding is
the main diagnostic tool. Duplex ultrasound may be used to identify direction of portal venous
blood flow and patency of the portal and splenic vein. Computed tomography (CT) and
magnetic resonance imaging are excellent modalities for evaluating patency of the portal and
splenic vein. These modalities are also useful in identifying the extensiveness of varicosities and
degree of ascites.
Treatment of Acute Esophageal and Gastric Variceal Bleeding

Treatment of patients with bleeding gastroesophageal varices requires prompt resuscitation,
hemodynamic support, and correction of hemostatic dysfunction. Once the patient is stabilized
the focus can be on diagnosis. Although variceal bleeding is common in patients with cirrhosis
who have acute upper gastrointestinal bleeding, other causes such as ulcer disease must be
considered. Esophagogastroduodenoscopy facilitates accurate diagnosis and immediate
endoscopic intervention.
Medical management is the initial treatment of choice to control variceal bleeding.
Pharmacotherapy and endoscopic therapy are usually the first attempts to control bleeding
unless otherwise contraindicated. -Blockers (thought to lower portal pressure), somatostatin,
and its analogue octreotide are used to stop and reduce instances of recurrent variceal
bleeding. Sclerotherapy and banding are the mainstays of endoscopic therapies. Most acute
variceal bleeding (>80%) is controlled in this manner. Balloon tamponade with the Sengstaken-
Blakemore tube may be used to control acute esophageal variceal bleeding. Published reports
of initial success in stopping esophageal variceal bleeding using this device range from 61% to
95% (46, 47, 48, 49, 50, 51). There is a high recurrence rate (>50%) of bleeding once the
Sengstaken-Blakemore tube is removed. Perforations, aspiration, ulcers, and strictures of the
esophagus are also associated with the balloon tamponade technique.
Pharmacologic Therapy
Somatostatin (natural peptide) or its synthetic analogues, octreotide and vapreotide, may
control variceal bleeding in 80% of patients; their mechanism of action is unknown but is thought
likely to be due to prevention of postprandial hyperemia or reduction of portal pressure by
effects on vasoactive peptides such as glucagons or substance P. Somatostatin and its
analogues all have few side effects when given intravenously and are often used instead of
vasopressin to control acute variceal bleeding. They may also be used without special
monitoring. Pharmacologic therapy is easy to administer and may be implemented adjunctively
to endoscopic therapy (52,53). Somatostatin is not available in the United States, but its
analogue octreotide is available. Octreotide's properties are similar to those of somatostatin,
however, it has a longer biological half-life. A recent meta-analysis demonstrated octreotide to
be superior to alternative therapies such as placebo, vasopressin/terlipressin, and
sclerotherapy in controlling acute variceal bleeding (53).
Endoscopic Therapy
Sclerotherapy and band ligation are effective in controlling acute esophageal variceal bleeding
and preventing rebleeding during hospitalization. The two modalities are considered the
mainstay of therapy and achieve hemostasis in 80% to 90% of patients with acute variceal
bleeding. Studies have shown the two modalities to be comparable in achieving initial
hemostasis (54). A recent study demonstrated that after initial control of bleeding, band ligation
had significantly fewer rebleeding episodes and complications and required fewer endoscopic
sessions than sclerotherapy (55). When feasible, band ligation should be the first-line
endoscopic therapy for acute variceal bleeding. The use of pharmacologic therapy in
combination with endoscopic therapy appears to be more efficacious than either therapy alone.
Surgery
Surgical options to control acute variceal bleeding include selective portosystemic shunting,
calibrated H grafts, and devascularization procedures. The 30-day mortality rate, however,
approaches 80% with these procedures (56). In most situations, surgical intervention for acute
variceal bleeding should be reserved for when medical therapy has failed and transjugular
intrahepatic portosystemic shunt (TIPS) is not available.
Transjugular Intrahepatic Portosystemic Shunt

TIPS is indicated in situations where acutely bleeding varices are refractory to medical therapy.
Much has been written regarding the technical aspect of performing TIPS (57, 58, 59, 60, 61).
Recent publications outline the technical aspect of performing TIPS when hepatic veins (Budd
Chiari) or the portal vein are occluded (62, 63, 64). Readers are referred to the literature and
the chapter on TIPS for further details.
Technical success in creating TIPS and reducing the hepatic venous pressure gradient (HVPG)
to 12 mm Hg can be expected in 95% of patients (65). Reducing the HVPG to 12 mm Hg
significantly reduces the likelihood of rebleed after TIPS. This threshold HVPG of 12 mm Hg for
variceal bleeding has been established as a result of data from several publications (66, 67, 68,
69). Recent data suggest that reducing the HVPG to 12 mm Hg may not be needed in all
instances to prevent rebleeding. Rossle et al. published data that revealed a probability of
rebleed rate of 18%, 7%, and 1% in patients whose HVPG was reduced by 0%, 25%, and
50% after TIPS (70). They concluded that a 50% reduction in the HVPG safely protected
patients from variceal rebleeding and a 25% reduction in the HVPG effectively reduced the
probability of variceal rebleeding to 7%.
Published mortality rates vary for TIPS in the setting of acute variceal bleeding; 30-day
mortality rates range from 15% to 78% (71, 72, 73). Several publications outline clinical criteria
for predicting mortality associated with TIPS to control acute variceal bleeding, (65,70, 71, 72,
73, 74, 75, 76). Emergent TIPS is an independent predictor of early mortality (73). Patients
with high model for end-stage liver disease (MELD > 24) or acute physiologic and chronic
health evaluation (APACHE II > 18) scores, high total bilirubin (>3), emergent versus elective
setting, or presence of pneumonia have been shown to have a higher early (60 days) mortality
rate following TIPS. This increased mortality rate is felt to be due to progressive liver disease.
Major procedural complications have been reported to be ~3%.
ACUTE LOWER GASTROINTESTINAL BLEEDING

Acute lower gastrointestinal bleeding implies blood loss (>2 units) of recent onset originating
from a site distal to the ligament of Treitz (6).
Etiology
The causes of acute lower gastrointestinal bleeding have been grouped into several categories:
anatomic (diverticulosis); vascular (angiodysplasias, ischemic, radiation induced), inflammatory
(infectious, idiopathic), and neoplastic (77). Colon carcinoma is the most common source of
lower gastrointestinal blood loss (78). Although inflammatory bowel diseases and neoplastic
bowel diseases may cause massive lower gastrointestinal bleeding, they are not the usual
source. This chapter discusses in detail only the clinical presentation and treatment of massive
bleeding due to diverticulosis and angiodysplasias.
Diverticular Bleeding
Diverticular bleeding accounts for 20% to 30% of cases of massive rectal bleeding and is the
most common cause of brisk maroon or bright-red blood per rectum (79,80). Bleeding occurs in
15% of patients with diverticulosis and a third of the time it will be massive (81). Most are
elderly patients with comorbid conditions that lead to combined morbidity and mortality rates of
about 10% to 20% (80,82). Bleeding stops spontaneously in 75% of episodes and in 99% of
patients who are transfused <4 units per day (83). The risk of rebleeding in this setting is 14%
to 38% (79,83).
Pathogenesis
A characteristic angioarchitecture is associated with bleeding colonic diverticula (Fig. 14-3). As
a diverticulum herniates, the penetrating vessel at that point becomes draped over the dome of
the diverticulum, separated from the bowel lumen only by mucosa. In time, the vasa recta gets
exposed to recurring injury along its luminal aspect, leading to eccentric intimal thickening and
thinning of the media. These changes may result in segmental weakness of the artery,
predisposing to rupture into the lumen (78). Rarely does bleeding occur in the setting of
diverticulitis (84). The right colon is the usual side of diverticular bleeding (50% to 90% of
patients), as opposed to the left side, where diverticulitis is most likely to occur (79,84,85). In
Western countries, 7% of all diverticula are left-sided, and when right-sided diverticula do occur
they are usually associated with left-sided diverticula (78,85). One explanation is that right-
sided diverticula have wider necks and domes, exposing a greater length of vasa recta to injury.
Another contributing factor may be the thinner wall of the right colon (81).
Patients have few, if any, abdominal symptoms, which is a reflection of the noninflammatory
pathogenesis of the bleeding. Symptoms and signs of diverticulitis are not present, since the
two disorders rarely coexist (84,86). Some patients may complain of bloating or cramping.
History may provide insight into the cause of bleeding. Hematochezia usually suggests a lower
gastrointestinal source; melena suggests a source proximal to the ligament of Treitz. There is
much overlap because massive upper gastrointestinal bleeding can present as hematochezia
(87), and melena may arise from the lower small bowel or proximal colon. Unless the patient is
hypotensive the physical exam may be unremarkable. In patients with acute lower
gastrointestinal bleeding, rectal examination, anoscopy, and proctoscopy are vital to the initial
management. These examinations are useful in ruling out massive hemorrhoidal bleeding.
Diagnosis
Once the bleeding source is determined to be within the lower gastrointestinal tract, endoscopy
is the initial examination of choice. Radionuclide imaging and mesenteric arteriography are other
useful diagnostic procedures. Each procedure has merits and disadvantages. Radionuclide
imaging is a noninvasive procedure that is very accurate for active bleeding, however, exact
localization of the bleeding site is difficult due to bowel peristaltic activity. The localization of a
bleeding site with mesenteric arteriography is very accurate and allows for immediate
treatment, however, it is invasive and requires the use of a contrast agent. Advantages of
colonoscopy include the potential
to precisely localize the site of bleeding and permit therapeutic intervention (32,88,89).
Disadvantages include poor visualization during massive bleeding or for a poorly prepared colon
and the risks of sedation in an acutely bleeding patient.
FIGURE 14-4. 99mTc-Pertechnetate-labeled red blood cell scan suggesting bleeding in the
right colon.
Two types of radionuclide scans are used to localize colonic bleeding: technetium (99mTc) sulfur
colloid and 99mTc pertechnetate-labeled red blood cells. Both techniques offer the advantages
of sensitivity and noninvasiveness. A sensitivity of 97%, specificity of 83%, and positive
predictive value of 94% have been reported using 99mTc-pertechnetate-labeled red blood cells
to localize lower gastrointestinal bleeding (90).
After injection of 99mTc-pertechnetate-labeled red cells, abdominal images are obtained serially
over a 30-minute period and then every few hours up to a 24-hour period (Fig. 14-4). This
technique allows the patient to be scanned several times over a 24-hour period. This is an
advantage since these patients tend to bleed intermittently.
Technetium sulfur colloid is rapidly cleared from the intravascular space; therefore, scanning
over the abdomen must be performed shortly after the intravenous injection. Bleeding rates as
low as 0.1 mL/minute can be detected. The short half-life requires the patient to be actively
bleeding at the time of isotope injection in order to identify bleeding. This is a disadvantage of
the technique when patients bleed intermittently.
Both nuclear medicine techniques for confirming and localizing site of bleeding have variable
rates of accuracy in localization (24% to 91%) (91). Colonoscopy is recommended prior to
nuclear medicine scanning in the evaluation of lower gastrointestinal bleeding because of its
higher diagnostic yield and the inaccuracy of localization by radionuclide imaging (6).
Radionuclide imaging is useful to determine which patients are bleeding and warrant emergent
selective mesenteric arteriography. Patients with a negative bleeding scan are likely to have a
negative selective mesenteric arteriogram (92). The fact that the patient may stop bleeding by
the time the scan is completed has been cited as a possible lost opportunity for a positive
selective mesenteric arteriogram (78,80).
Superior mesenteric arteriography is usually the first angiographic procedure performed to look
for an acute diverticular bleed. The majority of diverticular bleeds are in the right colon, and
unless otherwise directed one should inject the superior mesenteric artery first. It has been
reported that 50% to 80% of diverticular bleeds and all bleeds from proven angiodysplasias
occur in bowel supplied by the superior mesenteric artery (92). If the superior mesenteric
arteriogram is negative, an inferior mesenteric arteriogram should be performed. A Foley
catheter to keep the bladder empty is useful in preventing masking of a pelvic bleed by contrast
within the bladder. When both mesenteric arteriograms are negative a celiac axis arteriogram
should be performed. Success rates for identifying diverticular bleeding using mesenteric
arteriography range from 14% to 72% (32,80,81).
Mesenteric arteriography does not require bowel preparation and it is very accurate for
localization purposes. Mesenteric arteriography is usually reserved for patients in whom
endoscopy is not feasible or those with persistent or recurrent bleeding and nondiagnostic
endoscopy (6). It may also be used to treat the bleeding if the patient is not considered a
surgical candidate due to severe comorbid conditions or surgery is not available. Mesenteric
arteriography can detect bleeding rates >0.5 mL/minute and is 100% specific. Sensitivity
varies, ranging in one series from 47% for acute bleeding to 30% for recurrent bleeding (93).
Surgical exploratory laparotomy is considered to be the final diagnostic modality; a source of
bleeding is identified in 78% of patients without a preoperative diagnosis (94).
Treatment
Interventions to stop bleeding at the time of colonoscopy have included four-quadrant
epinephrine injections, tamponade, and bipolar coagulation (95). Endoscopic band ligation has
been performed and the results published (96).
Persistent instability despite aggressive resuscitation requires operative intervention and is
performed in 18% to 25% of patients who require transfusion for bleeding diverticular (82,97).
Segmental colectomy is performed when the source of bleeding has been localized; the rate of
rebleeding is 0% to 14% (80,82,98). Subtotal colectomy is reserved for the patient who
continues to bleed without a documented site of bleeding. Subtotal colectomy is associated
with high morbidity and mortality rates: 37% and 11% to 33%, respectively (80,82,99).
Preoperative localization of the site of bleeding and use of selective intra-arterial vasopressin
as a temporizing measure has reduced the operative morbidity from segmental colectomy to
8.6%, compared to 37% after emergent subtotal colectomy (80). Surgical mortality is ~10%
and is thought to be a reflection of comorbid conditions (80,94,97).
Arteriography, like colonoscopy, permits therapeutic intervention following diagnosis of bleeding
diverticula. Selective intra-arterial vasopressin infusion (Fig. 14-5) or embolization (Fig. 14-6)
may be performed via the indwelling diagnostic catheter. If a trial of vasopressin precedes
embolization, it is best to wait for ~30 minutes prior to embolization, to allow for relief of spasm
and a false-positive result after embolization.
Selective intra-arterial vasopressin infusion routinely begins at a rate of 0.2 unit/minute, with
repeat arteriography at 20 minutes (100). If bleeding persists the rate may be increased
incrementally up to 0.4 unit/minute; if bleeding is controlled, the infusion is continued, with
monitoring for signs of cardiac ischemia, mesenteric ischemia, or generalized vascular ischemia
for a period of 24 to 36 hours (100). Once bleeding has stopped for 12 to 24 hours, the intra-
arterial vasopressin infusing may be tapered at a rate of 0.05 unit/minute over the next 12 to 24
hours.
FIGURE 14-5. A 52-year-old female bleeding from diverticular disease. A: A catheter
selectively placed within the superior mesenteric artery (SMA) demonstrates bleeding
diverticula (arrow). B: Repeat SMA arteriogram after sliding-scale vasopressin infusion into
SMA at 0.4 unit/minute 3 hours, 0.3 unit/minute 3 hours, 0.2 unit/minute 12 hours, 0.1
unit/minute 6 hours, and 0.05 unit/minute 10 hours. Note the absence of contrast
extravasation. In an 89-year-old female, (C) SMA arteriogram revealed bleeding from a
diverticulum in the right colon, and (D) repeat SMA arteriogram 24 hours after vasopressin
infusion at 0.2 unit/minute showed that the bleeding had stopped.
FIGURE 14-6. An 89-year-old male with severe heart disease bleeding from diverticular
disease. A: Selective superior mesenteric artery arteriography revealed bleeding in the left
colon (arrow). B: Microcoils (thin arrow) placed very selectively into the branch artery with
a 3-Fr catheter (thick arrow). C: Coil is noted without adjacent bleeding.
Intra-arterial vasopressin therapy has been associated with major complications in 0 to 21% of
cases and up to 9% were fatal (101). Minor complications are more common and reports of the
frequency range from 10 to 41% (101). Reported associated cardiac complications range from
5 to 21% (102). Complications can include arrhythmias (bradycardia and ventricular
tachycardia), hypertension, angina, cardiac arrest, water retention, hyponatremia, mesenteric
venous thrombosis, systemic vascular ischemia or spontaneous bacterial peritonitis. Often it is
unclear whether to attribute these complications to vasopressin or the patient's comorbid
conditions. Discontinuing the vasopressin infusion will usually reverse any adverse effects.
Intravenous nitroglycerin infusion along with vasopressin therapy has been reported to
decrease cardiac effects and lessen the likelihood of major complications (101). Not
uncommonly, because of severe comorbid disease, the vasopressin infusion is tapered rapidly
within 24 hours of initiation.
Success in controlling diverticular bleeding can be expected in 80% to 90% of patients treated
with selective intra-arterial vasopressin infusion (103). Fifty percent of patients in two studies
rebled after stopping vasopressin infusion (80,104). However, selective intra-arterial
vasopressin infusion may serve to stabilize the patient's condition and allow for elective surgical
intervention.
FIGURE 14-7. A: 90-year-old female bleeding from a diverticulum in the splenic flexure of
the colon. A superselective superior mesenteric artery arteriogram reveals contrast
extravasation (arrow). B: Inferior mesenteric artery injection shows successful cessation of
the bleeding after microcoils were placed at the mesenteric border and vasa recti through
a selectively placed 3-Fr catheter.
For several years selective intra-arterial vasopressin infusion was the technique of choice to
control lower gastrointestinal bleeding when endoscopic or surgical intervention failed or was
unavailable. This was primarily due to the high incidence of reported bowel infarction associated
with selective intra-arterial embolization to control lower gastrointestinal bleeding (101). It is felt
that the high rate of infarction reflects the poor collateral arterial supply to the colon, and at that
time, the lack of availability of embolic agent to safely minimize blood flow to the bleeding site.
Recently selective distal embolization of colonic and jejeunal branches of the mesenteric
arteries to control lower gastrointestinal bleeding has begun to gain acceptance (101,105, 106,
107, 108, 109, 110, 111, 112). When it is successful the need for intensive monitoring is
alleviated and the patient may be returned to a regular floor for postprocedure care.
The availability of small guide wires (0.014 in.) and 3-Fr catheters (through which microparticles
such as polyvinyl alcohol [PVA] or microcoils may be injected) placed through 5-Fr guiding
catheters facilitates selective placement of embolic material into a single very distal branch at
the mesenteric border of the bowel wall or vasa recti (Fig. 14-7). It is this ability to deliver the
embolic material in such a selective manner to small distal branches that prevents infarction of
bowel and keeps ischemic complications to a minimum.
A number of embolic materials have been used to control bleeding in the mesenteric arterial
branches; they include autologous clot, Gelfoam pledgets, PVA particles, glue, and microcoils.
The integrity of autologous clot has proven difficult to sustain, Gelfoam pledgets are difficult to
deliver through 3-Fr catheters, and glue is difficult to control. Presently these agents are not
routinely used to selectively embolize mesenteric arterial branches to control lower
gastrointestinal bleeding. PVA particles >420 m have been used without causing bowel
infarction (101). However, they are not routinely used as the agent of choice for selective
mesenteric arterial embolization. Microcoils have become the agent of choice for many
interventional radiologists who routinely perform selective mesenteric embolization (112).
Because microils are radiopaque, localization is more definitive, unlike nonmetallic embolic
agents, which are not visible by x-ray. Microcoils come in various sizes, which allows for more
precise matching of the coil to vessel size. The precise fit of microcoils within the lumen of the
vessel may lead to less migration and inadvertent embolization to other structures. Recent
published technical success rates for selective embolization of mesenteric arterial branches
with microcoils to control bleeding have been noted to be 93% and 100% (112). Clinical
success using microcoils selectively placed within mesenteric arterial branches has been
reported to be as high as 96% (112).
Angiodysplasias
Angiodysplasias are the most common vascular anomalies occurring in the gastrointestinal
tract. One of the most common complications associated with angiodysplasias is bleeding. The
term angiodysplasias is synonymous with arteriovenous malformations and vascular ectasias.
Telangiectasias are referred to in the context of systemic or hereditary diseases and are
distinguished in that manner. Angiodysplasia refers to dilated tortuous submucosal vessels. The
walls of these blood vessels are composed of endothelial cells that lack smooth muscle. The
characteristic appearance of angiodysplasias has been identified through silicone casts of the
vessels (113). The casts reveal dilated tortuous submucosal veins as the most prominent
feature. Incompetence of precapillary sphincters leads to small arteriovenous communications.
In larger angiodysplasias large arteries are present, which may result in arteriovenous fistulae
and explains why bleeding may be brisk in some patients.
Angiodysplasia accounts for 20% to 30% of cases of hematochezia (80) and may be the most
frequent cause in patients >65 years of age (113,114). Histological examination demonstrates
dilated vessels in the mucosa and submucosa, sometimes covered only by a single layer of
surface epithelium (115). These features are shared by angiodysplasia in the colon and
stomach (116) and the small bowel (117).
Angiodysplasias occur throughout the gastrointestinal tract and may be multiple in one region or
coexist in many different locations. More than one lesion is present in about 40% to 50% of
patients (118,119). Only angiodysplasias actively bleeding at the time of endoscopy or
mesenteric arteriography can be reliably considered the source of bleeding because of the
prevalence of other lesions existing throughout the gastrointestinal tract (115,117). This has
implications when considering surgical or radiological interventions.
Etiology/Pathogenesis
Four theories have been proposed regarding the pathogenesis of angiodysplasia: chronic low-
grade venous obstruction may lead to the development of angiodysplasia (113). Complication of
chronic mucosal ischemia occurring during episodes of bowel obstruction or straining at stools
may lead to the development of angiodysplasia (120). Complication of local ischemia
associated with cardiac, vascular, or pulmonary disease may lead to the development of
angiodysplasia (121). Angiodysplasia may be congenital.
Angiodysplasias usually bleed in an occult fashion. Often there is a history of or prior
admissions for lower gastrointestinal bleeding. Not uncommonly they remain clinically silent,
however, they may present with acute massive episodic lower gastrointestinal bleeding.
Angiodysplasias of the stomach have been reported as the cause of overt bleeding in 27% of
patients (122). Angiodysplasias may be found throughout the small bowel. The colon is the
most common site of angiodysplasias in the gastrointestinal tract; colonic lesions are more
commonly found in the cecum and ascending colon but also may be found in other segments. A
published report that included 59 patients with colonic angiodysplasias revealed the following
distributions (123): cecum, 37%; ascending colon, 17%; transverse colon, 7%; descending
colon, 7%; sigmoid colon, 18%; and rectum, 14%.
Angiodysplasias of the colon account for about 20% to 30% of cases of acute lower
gastrointestinal bleeding, which is comparable in frequency to colonic diverticular bleeding (81)
and may be the most frequent cause of such bleeding in patients >65 years of age (113,114).
Patients who have bled from colonic angiodysplasias are at increased risk to rebleed (113).
Patients in the older population with certain predisposing conditions such as end-stage renal
disease, von Willebrand's disease, and aortic stenosis have an increased occurrence of
angiodysplasias. Angiodysplasia is the second most common cause of gastrointestinal bleeding
in elderly patients with end-stage renal disease (124). This associated condition accounts for
about 20% and 30% of upper and lower gastrointestinal bleeds, respectively (142), and about
one half of recurrent upper gastrointestinal bleeds (125). The reason for the increased
prevalence associated with patients with end-stage renal disease is unknown. These lesions
may be detected more frequently because of the increased risk of bleeding associated with
uremiainduced platelet dysfunction (115).
von Willebrand's disease (congenital or acquired) has been associated with angiodysplasias
(102,126). Similarly to end-stage renal disease, this association may reflect an increased
tendency for angiodysplasias to become clinically evident because of the underlying
coagulopathy.
Aortic stenosis in patients bleeding from angiodysplasias is referred to as Heyde's syndrome,
and many of its aspects remain controversial (127, 128, 129, 130, 131). Bleeding has been
reported to improve after aortic valve replacement (132, 133, 134, 135). Development of an
acquired form of von Willebrand's disease has been put forth in several publications as a
possible mechanism of bleeding in patients with angiodysplasias and aortic stenosis. The
mechanical disruption of von Willebrand multimers during turbulent flow through the narrowed
aortic valve, and von Willebrand factor interaction with platelets causes acquired platelet
deficiency and coagulopathy (135, 136, 137). Replacing the aortic valve in these circumstances
corrects bleeding and also reverses the hemostatic abnormalities in most patients (135,138).
Rebleeding may recur, especially if there is a patient-prosthesis mismatch.
Critics of the above von Willebrand factor hypothesis state that patients with angiodysplasia
and uncorrected aortic stenosis may simply be more inclined to bleed. They observe that
angiodysplasia persists after aortic valve replacement despite the cessation of bleeding
(116,139), the association of angiodysplasia with other bleeding disorders, such as end-stage
renal disease and other forms of von Willebrand disease, and the association of aortic stenosis
with bleeding at other sites leading to manifestations such as epistaxis and ecchymoses (135).
Baum et al. believe that angiodysplasias associated with aortic stenosis may be prone to
bleeding secondary to ischemic necrosis resulting from a low cardiac output (120). However,
others counter that other forms of heart disease that cause low cardiac output have not been
associated with bleeding angiodysplasias. Also, low cardiac output is a late-stage occurrence in
aortic stenosis (140).
Diagnosis
Angiodysplasias are usually diagnosed at endoscopy. They appear as 5- to 10-mm, cherry-red,
fernlike patterns of arborizing ectatic blood vessels radiating from a central vessel (115). The
pattern may be more evident in the colon since small bowel lesions appear much smaller. The
cherry-red fernlike pattern is the differentiating feature from other erythematous mucosal
lesions or normal blood vessels (141). The sensitivity of colonoscopy in detecting
angiodysplasias probably exceeds 80% (142).
Helical CT angiography (CTA) may provide another method to diagnose angiodysplasias (143).
Sensitivity, specificity, and positive predictive values of CTA for detection of colonic
angiodysplasias were 70%, 100%, and 100%, respectively. CTA signs including accumulation of
vessels in the colonic wall, early filling vein, and enlarged feeding artery were present in 55%,
50%, and 22% of cases, respectively. None of these signs were present in the eight patients
with obscure gastrointestinal bleeding and negative diagnostic investigation of the digestive
tract.
Selective mesenteric arteriography (Fig. 14-8) is the gold standard for diagnosing
angiodysplasias and permits intervention if bleeding cannot be controlled endoscopically or if
surgery is unavailable or too risky. Characteristically a clustering of vessels in the precapillary
phase and an early-appearing draining vein located in the right colon are the hallmarks of
angiodysplasia. Angiographic intervention may be utilized as a temporizing measure to prevent
emergent surgery. Localized angiodysplasia demonstrated to be actively bleeding at selective
arteriography may be embolized. For localized angiodysplasia found not to be actively bleeding
selective intra-arterial vasopressin for 24 hours may be tried.
Treatment
Actively bleeding angiodysplasias must be treated. The finding of lower gastrointestinal
angiodysplasia in an individual who has stopped bleeding poses a dilemma, particularly if the
patient is also known to have diverticular disease. This clinical scenario is common since both
occur in the same age group. Bleeding in this setting is more likely to be diverticular in origin in
patients bleeding from the left colon. Bleeding from angiodysplasias is nearly always from the
cecum or ascending
colon. However, diverticular bleeding is also more common in the right colon.
FIGURE 14-8. A: Diagnostic superior mesenteric artery arteriogram revealing cecal

angiodysplasia in an 81-year-old male with a chronic history of lower gastrointestinal
bleeding. Note the early draining vein (arrow) and clustering of small arterial branches at
the antimesenteric border (small arrowheads) of the cecum. B: Late draining vein (arrow)
noted in the same series of images. The patient was taken to surgery for resection.
Bleeding from angiodysplasias is also more likely in patients with a history of multiple recurrent
episodes of acute bleeding, end-stage renal disease, aortic stenosis, von Willebrand's disease,
or bleeding of venous origin. A variety of endoscopic treatments can be used to treat
angiodysplasias. Bipolar or heater probe coagulation is said to be effective for treatment of
angiodysplasias in the colon or upper gastrointestinal tract (144). Injection of a sclerosant
(sodium tetradecyl sulfate or ethanolamine) has been used to obliterate lesions in the upper
gastrointestinal tract and colon (145,146). Lasers have also been used to treat angiodysplasias
(147,148).
Surgical resection is definitive for angiodysplasia lesions that have been clearly identified as the
source of bleeding. Recurrent bleeding may occur from lesions elsewhere in the gastrointestinal
tract (80,144,149). In a series that included 16 patients who underwent right hemicolectomy for
bleeding from angiodysplasias, unexplained recurrent bleeding developed in 6 (37%) (149).
Selective mesenteric angiography may localize the site of active bleeding and permit
embolization or infusion of vasopressin to stop bleeding. Embolization may be more successful
than vasopressin in controlling bleeding from angiodysplasias, however, it is associated with a
higher complication rate. Angiography is usually reserved for patients with life-threatening
bleeding who are not surgical candidates or for those in whom localization of lesions is desired
prior to surgical resection (150).
CONCLUSION
The literature (41,80,109,149, 150, 151, 152, 153, 154) suggests that the clinical outcome of
angiographic techniques to control upper and lower gastrointestinal bleeding depends on the
source. Reported success rates with selective intra-arterial vasopressin infusion and selective
arterial embolization, respectively, are as follows: gastric lesions, 62% and 66%; gastritis and
stress ulcers, 69% and 78%; Mallory Weiss tears, 74% and 82%; and lower gastrointestinal
lesions, as high as 90% and 100%. Published quality improvement guidelines for percutaneous
transcatheter embolization cite an overall major complication threshold of 15% (154). No overall
major complication threshold has been published for intra-arterial vasopressin.
In light of the literature cited it is this author's opinion that angiography is a potent and important
modality for the diagnosis and treatment of acute gastrointestinal bleeding.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 15 - Visceral Artery
Anevrysms: Endovascular Management
Chapter 15
Visceral Artery Anevrysms: Endovascular
Management
Thomas A. Shin
Klaus D. Hagspiel
Visceral artery aneurysms comprise a rare but clinically important vascular disease entity. Their
incidence, etiology, and natural history are incompletely understood, and patients frequently
present as clinical emergencies (1). It is in these circumstances that interventionalists are often
called on to utilize their expertise in treating these patients. The rarity of these lesions has
prohibited any large studies with concomitant long-term follow-up to assess the durability of
endovascular management. That being said, endovascular intervention is rapidly becoming first-
line treatment, with surgery playing an important but secondary role only when endovascular
techniques fail or cannot be performed.
The visceral arteries include the three main unpaired branches of the abdominal aorta. These
are the celiac, superior mesenteric, and inferior mesenteric arteries along with their branches.
Shanley and Stanley's considerable work has contributed to our current understanding of
visceral artery aneurysms. The prevalence of visceral artery aneurysms in reported autopsy
series ranges from 0.01% to 10% (2). They involve, in descending order, the splenic (60%),
hepatic (20%), superior mesenteric (5.5%), celiac (4%), gastric and gastroepiploic (4%),
intestinal (jejunal, ileal, colic; 3%), pancreatico-duodenal and pancreatic (2%), gastroduodenal
(1.5%), and inferior mesenteric arteries (rare) (Fig. 15-1). A more recent review of the English
literature published between 1985 and 1995 showed that hepatic arteries were the most
frequently affected vessels. This was felt to be partially if not entirely due to iatrogenic
aneurysms resulting from the rapid increase in percutaneous or laparoscopic biliary procedures
(3). As the clinical behaviors of visceral arterial aneurysms are unpredictable, more aggressive
approaches are being advocated today.
Aneurysm size has not always been shown to be predictive of relative risk. A diameter of 2 cm
is often cited in the surgical literature as large enough to merit consideration of treatment.
However, there is no clear consensus on size thresholds, as even small aneurysms have been
known to rupture. Some authors have extrapolated research on aortic and iliac aneurysms to
visceral aneurysms. In the aorta and iliac arteries it has been shown that once the aneurysm
diameter reaches twice the normal vessel diameter, the risk for rupture increases sufficiently to
warrant treatment (4). Pseudoaneurysms, on the other hand, warrant a much lower threshold
for intervention and are often treated regardless of size or symptoms due to the fragility of their
wall.
The traditional treatment for these lesions has been surgical. Ligation and exclusion or
aneurysmectomy (without arterial reconstruction) are the most frequently employed surgical
techniques in the proximal and midsegment of the splenic artery. Proximal and distal ligation
limits blood loss once the aneurysm sac is opened and then branches that may be back-
bleeding into the aneurysm can also be ligated. This treatment is very effective at preventing
any future possibility of aneurysm-related complications or death. Perfusion to the spleen is
maintained via the short gastric arteries, so splenic infarction is rare. Primary reconstruction
and aneurysmorrhaphy can be applied to many locations of splanchnic artery aneurysms.
Proximal and distal control of the involved artery must be achievable and dissection is carried
out until there is enough artery length to allow primary anastomosis of the arterial ends once
the aneurysm is resected. If a limited circumference of arterial wall is involved with the
aneurysm, another option can include aneurysmorrhaphy and closure of the arterial defect using
a vein patch.
Aneurysm exclusion and bypass grafting are most frequently used to maintain perfusion to the
liver and intestine when simple aneurysmorrhaphy or primary repair is not technically feasible
for aneurysms in locations that require revascularization. These locations most commonly
involve the hepatic and mesenteric arteries. Conduit choices include the saphenous vein, which
is a good size match with splanchnic arteries and should be the conduit of choice for
contaminated cases. Synthetic grafts can also be used as a conduit for bypass grafts in these
locations.
Endovascular options have been developed to augment the arsenal of available interventions for
these heterogenous lesions. However, durability for many percutaneous interventions has not
been completely evaluated. Endovascular treatment needs to be tailored to the specific
anatomical situation. This chapter reviews the current endovascular treatment options, which
include embolization, stent-grafting, and thrombin injection. This is followed by discussion of the
specific considerations for the splenic, hepatic, and superior mesenteric arteries (SMAs).
ENDOVASCULAR TREATMENT
Embolization
The first and still most widely utilized endovascular management technique for visceral artery
aneurysms is percutaneous transcatheter coil embolization (PTCE). This is sometimes used in
conjunction with liquid polymers such as cyanoacrylate glue. Other, less often used means of
embolization include release of detachable balloons and injection of particulate materials such
as PVA and Gelfoam. Embolization is generally used if patency of the parent vessel is not
crucial. There is no consensus on which one of these techniques or combination of techniques is
best. Complications are rare and short-term success appears to
be high, without the concomitant morbidity of major abdominal surgery (4).
FIGURE 15-1. Prevalence of visceral artery aneurysms.
The site of the lesion, its size, its cause, the characteristics of the aneurysm wall, and the
quality of the collateral circulation together dictate the approach and the material to be used.
Most investigators prefer nonabsorbable materials for embolization unless severe ischemia of
the organ is likely (5).
As with any endovascular procedure, careful planning prior to initiation is essential. Cross-
sectional imaging using computed tomography (CT) or magnetic resonance (MR) with
dedicated vascular sequences is preferred. Among the features to look for, morphology is
perhaps the most important. Favorable aneurysm morphology for PTCE includes saccular
aneurysms with narrow necks (Type I), fusiform aneurysms with adequate collateral flow (Type
II), and aneurysms of vessels that are not the only source of arterial flow to the end organ
(Type III) (6). Because end-organ ischemia or infarction is possible and in some cases
anticipated, the determination of aneurysm location and its relationship with adjacent vessels
should be as specific as possible. For instance, embolization of the common hepatic artery may
not result in end-organ ischemia if the gastroduodenal artery is available to provide collateral
flow to the liver. Some of these features will best be delineated on a diagnostic angiogram prior
to the initiation of treatment.
Superselective catheterization using coaxial microcatheters is the method of choice, particularly
if particulate or liquid polymer injection is anticipated. Saccular aneurysms with narrow necks
might be amenable to treatment with aneurysm coil packing while maintaining patency of the
parent vessel. With fusiform aneurysms, wide-neck saccular aneurysms, or saccular aneurysms
not amenable to selective catheterization, coil embolization of the afferent and efferent vessels
is the technique of choice. It is essential to occlude both inflow and outflow to completely
exclude flow into the aneurysm (Fig. 15-2).
Whichever approach is used, it is important to keep the tenuous nature of aneurysms in mind.
The vessel walls are fragile, often have diseased intima, elastic lamina, and/or media, and can
easily rupture if delicate techniques are not used. This is particularly true in pseudoaneurysms,
where the vessel wall is by definition already compromised. When dealing with false
aneurysms, the operative mortality tends to be high, with some reports as high as 35% for the
splenic artery and 21% for the hepatic artery (7). The lowest amount of force should be used,
especially if coils are being deployed inside the aneurysm cavity, since an increase in
intraluminal pressure increases the risk of rupture.
It is important to keep in mind that contrast flow though the aneurysm sac is not uncommon
after coil placement, mainly because most patients are anticoagulated with heparin during the
procedure (7).
Technical success in treating visceral artery aneurysms with PTCE has been reported to be as
high as 75% to 92% (4,7) with most failures being due to the inability to catheterize the
aneurysm neck or feeding vessel. Other complications relate to nontarget embolization from
misplaced coils, embolization of the wrong vessels, dissection, and perforation. Surprisingly,
very few reports of procedure-related rupture were found in our literature search. Most adverse
effects were not unexpected and relate to sequelae of end-organ infarction such as fever, pain,
nausea, and leukocytosis in the immediate postprocedure period and, very rarely, abscess
formation weeks later.
Despite the fact that long-term follow-up data are lacking, it is clear that close follow-up should
be performed for an indeterminate period of time. Long-term complications include continued
enlargement and/or recanalization despite technical successes. Coil compaction has also been
reported (8) and theoretically has a higher incidence in wide-neck aneurysms, which allow
hemodynamic forces to act on the larger surface areas of the coil ball. Aneurysm rupture has
been reported after procedures in which total obliteration was apparently obtained (9).
Ultrasonography with color Doppler or any other noninvasive vascular imaging technique to
confirm thrombosis of the aneurysm is frequently performed after embolization in our practice.
Whenever possible, transcatheter embolization is the treatment of choice in visceral artery
aneurysms due to its proven efficacy, low morbidity and mortality, and relative ease of
performance. It is advantageous over surgery since it is possible to precisely locate the
aneurysm and to assess the collateral flow, and because of the inherent minimal invasiveness
associated with endovascular techniques. Even in those cases in which surgery is preferred,
embolization may be indicated as a temporary procedure to delay surgery in high-risk patients
and as a definitive and immediate method to control hemorrhage (4).
Stent-Grafting
The use of stent-grafts for the treatment of aortic and peripheral aneurysms is well established.
Their use for visceral artery aneurysms has been described in a number of small series and
case reports. Improved stent-graft flexibility and smaller delivery systems have eclipsed the
traditional limitation of these devices. Given the effectiveness of embolization therapies in the
treatment of visceral artery aneurysms, stent-graft repair is still relatively uncommon.
Preservation of arterial flow is a distinct advantage of stent-grafting over standard embolization,
and therefore stentgrafting should be considered in patients in whom adequate collateral flow is
not present. Examples include lesions in the proper hepatic or distal SMAs. Stent-grafting
should also be considered when end-organ ischemia or infarction would be an unacceptable
consequence of embolization treatment. For example, in liver transplant patients, where arterial
perfusion to the parenchyma and biliary system is critical, stentgrafting is preferred.
FIGURE 15-2. A: CTA shows a large splenic artery aneurysm. B: Abdominal aortogram
prior to intervention. C: Selective arteriogram demonstrates cephalad (long arrow) and
caudad (short arrow) efferent vessels emanating from the aneurysm. D: Arteriogram
through a coaxial microcatheter placed in the caudad efferent vessel. E: Arteriogram
performed following coil embolization of the caudad efferent vessel. F: Reverse curve
catheter arteriogram of the larger cephalad efferent vessel. G: Arteriogram performed
following coil embolization of the cephalad efferent vessel. H: Postprocedure arteriogram
following embolization of the afferent artery using an Amplatzer Vascular Plug (AGA
Medical Corp., Golden Valley, MN) occlusion device. I: Postprocedure CTA shows
successful thrombosis of the aneurysm.
Treatment planning is ideally performed with either CT angiography (CTA) or catheter

angiography. The caliber of the artery both proximal and distal to the aneurysm and the neck
length of the aneurysm must be known precisely (Fig. 15-3).
The tortuosity of visceral arteries can make placement of covered stents technically
problematic. However, the use of stiff guide wires, guide catheters, and sheaths proves to offer
sufficient trackability (10) for proper positioning of the stent-graft. Furthermore, self-expandable
rather than balloon expandable stents are preferred within tortuous segments, as self-
expandable stents can better conform to the contours of the artery.
The first description of stent-graft treatment of a visceral artery aneurysm was by McGraw et
al. in 1998 (11). A custom-made autogenous vein covered Palmaz stent was used to treat an
SMA pseudoaneurysm. Autogenous vein covered stents have been used in only a handful of
situations and are theoretically preferred for treatment of infected pseudoaneurysms. However,
PTFE covered stents have been successfully used in similar scenarios, with good results (12).
We have used several different covered stents in the treatment of visceral artery aneurysms,
each with its own features (Fig. 15-4). Viabahn (W. L. Gore Medical Products Division,
Flagstaff, AZ) stent-grafts are self-expandable and consist of an external Nitinol stent with
ePTFE lining. They are available in 6- to 8-mm diameters, with lengths ranging from 25 to 150
mm.
Fluency (Bard Peripheral Vascular Inc., Tempe, AZ) stentgrafts are also self-expandable and
consist of a Nitinol skeleton enveloped within two layers of ePTFE with a carbonlined luminal
surface, which the manufacturer claims improves biocompatibility. They are available in 6- to
10-mm diameters, with lengths ranging from 40 to 80 mm.
iCast (Atrium Medical Corp., Hudson, NH) stent-grafts are balloon expandable and consist of a
stainless-steel stent encapsulated in microporous PTFE. They are available in 5- to 12-mm
diameters, with lengths ranging from 16 to 59 mm. Their delivery systems have the low profiles,
utilizing either 6- or 7-Fr sheaths.
Jostents (Abbott Laboratories, Abbott Park, IL) are balloon expandable and consist of a
stainless-steel stent and PTFE. They are the only device listed here that utilizes 0.018-in.
systems. They are available in 3- to 5-mm diameters, with lengths ranging from 12 to 26 mm.
FIGURE 15-3. A: Patient with a large aneurysm of the celiac trunk. CTA with multiplanar
reformatted reconstruction shows the anatomy and allows measurement of vessel
diameter before initiation of treatment. B: Positioning of the stent-graft prior to
deployment. C: Postdeployment angiogram demonstrating exclusion of the aneurysm using
a Fluency (Bard Peripheral Vascular Inc., Tempe, AZ) stent-graft. Note embolization of the
left gastric artery in order to prevent Type II endoleak. D: Follow-up CTA shows exclusion
of aneurysm, patency of the stent, and preservation of vessel perfusion distal to the stent-
graft.
Wallgraft (Boston Scientific, Natick, MA) devices are self-expandable and consist of a
supermetal alloy covered end-to-end with polyethylene terephthalate. They are the only device
listed here with reconstrainable and repositionable delivery systems. They are available in 6- to
14-mm diameters, with lengths ranging from 20 to 70 mm.
A number of small studies and case reports have shown good technical results with satisfactory
exclusion of visceral artery aneurysms. At our institution, stent-graft treatment of 12 visceral
aneurysms in 12 patients resulted in 100% technical and 100% clinical success, without
significant complications. Primary patency was 63%, and secondary patency was 73% after a
mean follow-up of 287 days. Three patients had occlusion of their stent-grafts, and in all the
vessel diameters were 5mm (13). A single case report of a 5-year symptom-free period after
stent-grafting of an SMA pseudoaneurysm is the longest known follow-up after this treatment
(12). It is clear that patient selection based on adequate arterial anatomy, location, and degree
of tortuosity are the key elements for success. Close follow-up with regular imaging using color
Doppler or cross-sectional modalities is recommended. Unfortunately, the long-term durability
of stent-grafts in the treatment of visceral artery aneurysms is unknown.
Thrombin
Percutaneous thrombin injection to treat visceral artery aneurysms is performed relatively
infrequently. Cope et al. introduced the concept of direct percutaneous injection of diluted
thrombin for coagulation of pseudoaneurysms of the iliac, femoral, and peroneal arteries. In
1986, percutaneous thrombin treatment of an accessory hepatic artery aneurysm was
described (14). Since then, percutaneous injection of thrombin into puncture-related
pseudoaneurysms of the common femoral artery has found widespread acceptance. Its use in
visceral artery aneurysms may be indicated in select cases.
Bovine thrombin-collagen compound is approved for management and control of bleeding from
vascular access sites, percutaneous catheters and tubes, and tissue tract oozing. D-Stat
Flowable Hemostat (Vascular Solutions Inc.) is a procoagulant, flowable mixture of thrombin,
collagen, and a diluent, which is designed to accelerate the blood-clotting process by facilitating
conversion of fibrinogen to fibrin clot. It is not approved for intravascular use (15).
FIGURE 15-4. A: Viabahn (W. L. Gore Medical Products Division, Flagstaff, AZ). B:
Fluency (Bard Peripheral Vascular Inc., Tempe, AZ). C: iCast (Atrium Medical Corp.,
Hudson, NH). D: Jostent (Abbott Laboratories, Abbott Park, IL). E: Wallgraft (Boston
Scientific, Natick, MA).
FIGURE 15-5. A: Color Doppler ultrasound image of an inferior epigastric artery
pseudoaneurysm as a complication of laparotomy. B: Hand injection of contrast through a
needle prior to thrombin injection. C: Post-thrombin injection color Doppler ultrasound
image showing successful thrombosis of the aneurysm.
As percutaneous thrombin injection offers no particular advantage over embolization or stent-

grafting, it should only be performed in those patients in whom endovascular techniques are not
possible or have failed. Suitable morphology is confined to saccular aneurysms with narrow
necks. Fusiform or wide-neck aneurysms are unlikely to confine thrombus formation within the
aneurysm itself. Also, it should only be considered when safe placement of a needle into the
aneurysm is possible. This is best done using ultrasound with color Doppler or, occasionally,
CT.
Percutaneous thrombin injection of visceral aneurysms is preferably made in conjunction with a
catheter placed in the proximal artery so that the presence and proper morphology of the
aneurysm can be confirmed. Using ultrasound guidance, an appropriate length needle is
inserted into the aneurysm with the needle tip a comfortable distance away from the neck.
Placement is confirmed with blood return and if needed, a small hand injection of contrast
through the needle. Slow, careful injection of the prepared thrombin solution under real-time
color Doppler ultrasound imaging is done. This is intermittently performed with angiography to
assess aneurysm flow until adequate thrombosis is achieved (Fig. 15-5).
Some modifications of this procedure include placing an occlusion balloon across the neck of
the aneurysm during injection. This has been advocated to protect the arterial lumen (16). The
potential for in situ thrombus formation around the balloon and in the donor artery during balloon
inflation, in addition to arterial spasm after balloon deflation make this option less attractive
(17).
Complications of percutaneous thrombin to treat visceral aneurysms relate to inadvertent
injection into the native artery. With meticulous patient selection and careful, slow injection, this
can usually be prevented. As a foreign substance, bovine thrombin has the potential for inducing
an allergic response in an unknown percentage of patients. Furthermore, the development of
bovine thrombin-induced antibodies is another possible complication of this procedure which can
lead to Factor V deficiency (15).
Short-term follow-up imaging using color Doppler ultrasound or cross-sectional modalities is
indicated since insufficient data exist regarding the effectiveness of this treatment. Only
scattered case reports exist, which all show good technical success with low complication
rates, however, long-term follow-up data are not available.
SPLENIC ARTERY
Epidemiology
Splenic artery aneurysms are the most common visceral artery aneurysms. The true incidence
of these lesions in the population is unknown, with autopsy reports ranging anywhere from
0.1% to 7.1%. They are found incidentally in 0.78% of abdominal arteriograms (18). Most
splenic artery aneurysms are saccular and more than 80% are located in the mid or distal
splenic artery (4). The average reported ages of patients with splenic aneurysms range from
48 to >60 years. Splenic artery aneurysms are found twice as frequently in woman as in men,
with this female predominance being specific to the splenic artery. Twenty percent of splenic
artery aneurysms are multiple (19).
The reported risk of rupture of splenic artery aneurysms varies from 3.0% to 9.6% (20, 21,
22), with a mortality rate after rupture ranging between 10% and 25% (23). The risk is
significantly higher in women during pregnancy, with dismal survival rates for both the mother
and the fetus.
Etiology
The exact mechanism behind aneurysm formation is not clearly understood. Causes can be
divided into four categories: degenerative, inflammatory, posttraumatic, and pregnancy related.
In contrast to aneurysms of large vessels, atherosclerosis is not considered to be the primary
etiological factor for splenic aneurysms (7,20). Degenerative aneurysm formation from
underlying medial fibrodysplasia is one possible mechanism. For unclear reasons but perhaps
due to increased splenic artery perfusion, patients with portal hypertension and splenomegaly
have also been found to have a higher incidence of splenic artery aneurysms. Because of this,
aneurysms are frequently discovered in patients being evaluated for liver transplantation.
Inflammatory pseudoaneurysms are almost always associated with pancreatitis and the
presence of pseudocysts. Leaked digestive enzymes followed by autodigestion and weakening
of the arterial walls can lead to subsequent pseudoaneurysm formation. Very rarely,
pseudoaneurysms are caused by other regional inflammatory diseases such as peptic ulcer
disease. Polyarteritis nodosa is another known inflammatory etiology, although the splenic
artery is less commonly involved than other locations.
Posttraumatic splenic artery pseudoaneurysm formation from penetrating injuries is uncommon.
Rapid deceleration can result in splenic arterial injury due to damage of the intima and elastic
lamina (24). Iatrogenic trauma secondary to postoperative anastomotic leakage after
pancreatic surgery (especially pancreatoduodenectomy) is another well-known cause of
pseudoaneurysm formation (25).
Splenic artery aneurysm formation during pregnancy or in multiparae is perhaps the most
clinically important given the high associated mortality for both the mother and the fetus.
Mortality rates are as high as 75% in pregnant mothers with ruptured aneurysms (26). Some
believe that the increased blood volume and portal congestion account for this association (20).
Others believe that pregnancy-related hormonal changes cause hyperplasia of the intima and
fragmentation of the internal elastic membrane to which the splenic artery is particularly
susceptible (23).
Diagnosis
Symptoms due to aneurysm rupture are often times overlooked if the presence of an aneurysm
is not known. The detection of a hemorrhaging aneurysm is complicated by the fact that they
can extravasate into either the peritoneal space or the retroperitoneum. They can also fistulize
into bowel, the biliary system, or the splenic vein. Severe pain, unexplained anemia, recurrent
GI bleed, hemodynamic instability, or other signs and symptoms of hemorrhage should
immediately alert one to the possibility of rupture in a patient with a known aneurysm.
More specific is enlargement of a pseudocyst or the presence of blood at the ampulla of Vater
(27). A characteristic sequence of events involves a patient with known pancreatitis and
pseudocysts. Leaked pancreatic enzymes damage the adjacent splenic artery, which ruptures
into and enlarges the pseudocyst. Hemorrhage can extend into the pancreatic duct, termed
hemosuccus pancreaticus, followed by massive bleeding into the GI tract.
More difficult clinical presentations involve patients with nonruptured aneurysms who have
vague abdominal complaints over the course of days to years. These complaints are often
attributed to other more common etiologies, which can be due to a myriad of entities.
Although clinical signs and symptoms are helpful, the majority of aneurysms are found
incidentally on imaging performed for other causes. CTA is the best study in our opinion. MR
imaging/MR angiography is less sensitive. Ultrasound is limited in the evaluation of the
peripancreatic region due to overlying bowel gas. Angiography is also well suited, although
aneurysms can be overlooked, particularly if they are partially thrombosed. Infrequently,
aneurysms can be diagnosed on plain radiographs of the abdomen if curvilinear calcifications
are found in the epigastric region.
Treatment
Most of the surgical literature recommends repair of splenic artery aneurysms when they are
larger than 2 cm or are found to have enlarged. Because of the tendency of splenic artery
aneurysms to rupture late in pregnancy, with high fetal and maternal mortality rates, treatment
is indicated in pregnant patients or in women of childbearing age who might become pregnant
(2,22). Some have advocated repair of splenic artery pseudoaneurysms regardless of size or
symptoms (24).
Traditionally, splenic artery aneurysms were treated surgically with ligation or aneurysm
resection. This involves exposure of the lesser sac and control of the normal splenic artery
proximal and distal to the aneurysm (18). In patients with splenic artery pseudoaneurysms
associated with pancreatitis, surgical treatment often involves splenectomy and partial
pancreatectomy. The reported mortality associated with surgery is 1.3%, with a morbidity of
9% (23).
Endovascular treatment of splenic artery aneurysms usually involves embolization or stent-graft
placement. Particulate materials such as Gelfoam are not very popular for use in these
locations and should be avoided altogether in the pancreatic region, where proteolytic
enzymatic digestion may cause reabsorption in only a few hours (5). The most common
complication of splenic aneurysm treatment is splenic infarction, which can cause
postembolization syndrome in the early postprocedure period, and splenic abscess weeks later.
This can be avoided by using a stent-graft which preserves flow (Fig. 15-6). If splenic infarct is
inevitable, then analgesia with narcotics or nonsteroidal anti-inflammatory drugs is indicated.
Pneumococcal vaccine should also be administered prior to patient discharge.
HEPATIC ARTERY
Epidemiology
Hepatic artery aneurysms were traditionally considered the second most frequent visceral
aneurysms, although some debate exists as to whether they have now become the most
frequent ones. This is thought to be attributable to the increased utilization of percutaneous and
laparoscopic biliary procedures (6) which can be complicated by hepatic artery injury. Recent
data have contradicted older studies which showed that 80% of hepatic artery aneurysms are
extrahepatic in location. Newer
studies have shown that only 66% reside extrahepatically (19). Shanley et al. report that
between 1985 and 1995, over 50% of all hepatic artery aneurysms were false aneurysms of
the intrahepatic arterial branches (19). They are more common in men than women, and most
hepatic artery aneurysms are solitary.
FIGURE 15-6. A: Maximum intensity projection of an abdominal CTA reveals a mid-splenic-
artery aneurysm. B: Intraprocedural angiogram demonstrating the aneurysm. C:
Successful exclusion of the aneurysm using a Viabahn (W. L. Gore Medical Products
Division, Flagstaff, AZ) stent-graft with preservation of distal perfusion.
The precise risk of rupture is not known. However, given that a majority of hepatic artery
aneurysms are false aneurysms, the risk should be considered higher than in aneurysms of the
splenic artery. The reported mortality of hepatic aneurysm rupture is as high as 21% (2,19).
Etiology
Hepatic artery aneurysms are usually the result of penetrating, iatrogenic, or blunt trauma.
Iatrogenic trauma by way of liver biopsy, percutaneous transhepatic cholangiogram, ERCP,
biliary tube placement, laparoscopic cholecystectomy, or other biliary surgeries accounts for
the increasing incidence of hepatic artery aneurysms.
Other less common etiologies include atherosclerotic disease with medial degeneration and
infection. Mycotic aneurysms are usually found in patients with a history of intravenous drug
abuse. Rare causes are from vasculitides such as polyarteritis nodosa and periarterial
inflammation caused by either cholecystitis or pancreatitis (18). Fibromuscular dysplasia and its
variant, segmental mediolytic arteriopathy are other noninflammatory etiologies often
overlooked.
Diagnosis
Hepatic artery aneurysms are often asymptomatic, but many present with pain in the right
upper quadrant, jaundice and/or elevated liver enzymes, which can complicate accurate
diagnosis. Jaundice and elevated liver enzymes are presumably caused by extrinsic
compression of the biliary system by the aneurysm itself. If a patient had recent blunt or
penetrating abdominal trauma, one should carefully interrogate the hepatic vasculature on
imaging to evaluate for the presence of a pseudoaneurysm. Furthermore, if the patient had
recent surgery or other intervention with signs and symptoms localizable to the liver,
pseudoaneurysm formation should be considered. (Fig. 15-7).
FIGURE 15-7. A: Abdominal CT showing a large post-hepatic artery pseudoaneurysm as a

complication from cholecystectomy. B: Celiac artery arteriogram prior to intervention. C:
Color Doppler ultrasound image of the pseudoaneurysm prior to thrombin injection. D:
Post-thrombin injection color Doppler ultrasound image shows thrombosis of the
pseudoaneurysm. E: Follow-up CTA demonstrates recanalization of the pseudoaneurysm.
F: Arteriogram of the hepatic artery demonstrates perfusion of the pseudoaneurysm sac
(arrows). G: Successful exclusion of the pseudoaneurysm using a Jostent (Abbott
Laboratories, Abbott Park, IL) stent-graft. H: Follow-up CTA 2 days postplacement
confirms complete thrombosis of the pseudoaneurysm.
Unfortunately, most patients with hepatic artery aneurysms present with rupture. In one study,
80% of patients with hepatic artery aneurysms presented with rupture (28). The aneurysms
usually rupture into the biliary system or the peritoneal cavity, and this is associated with a very
high mortality (29). Quincke's triad is the classic finding of hepatic aneurysm rupture and
consists of epigastric pain, hemobilia, and obstructive jaundice.
Hepatic artery aneurysms are frequently found incidentally, but less so than those of the splenic
artery. CTA is the best noninvasive modality to assess for the presence of hepatic artery
aneurysms, as it allows one to detect and define the aneurysm anatomy. It also allows precise
localization, a feature that is paramount if surgery is planned. Less sensitive imaging modalities
include MR imaging/MR angiography and ultrasound. Angiography is very useful in delineating
the regional arterial anatomy, key for planning an endovascular approach to treatment.
Treatment
Hepatic artery aneurysms have a relatively high risk of rupture, therefore an aggressive
approach to their management is recommended. Some authors call for treatment of all hepatic
artery aneurysms even when asymptomatic, with exceptions being made when the patient is
very old or very high risk (18).
Surgical management of hepatic artery aneurysms must take into consideration their precise
location. Extrahepatic aneurysms are easier to expose than intrahepatic ones. Repair usually
consists of aneurysmorrhaphy with restoration of hepatic arterial flow using arterial
reconstruction via saphenous vein or prosthetic graft. Direct aortohepatic bypass is another
option. Intrahepatic aneurysms are much more difficult and can involve partial liver resection.
Ligation is sometimes considered, with distal liver infarction an accepted consequence.
Transcatheter embolization can be safely performed if the patient does not have portal
hypertension, the portal vein is patent, and the hepatic collateral arterial routes are not altered
(29). Thus the vast majority of hepatic artery aneurysms can be managed with percutaneous
transcatheter coil embolization (30). Occlusion of the common hepatic artery can be safely
performed if one is assured that collateral flow from the gastroduodenal artery is present. If
this is not the case or if the involved vessel is distal to the gastroduodenal artery, then stent-
grafting is recommended.
SUPERIOR MESENTERIC ARTERY

Epidemiology
SMA aneurysms are the third most common visceral aneurysm, accounting for 5.5% of these
lesions. They almost always involve the proximal 5 cm of the main SMA trunk. The SMA is the
most common site for infection of a peripheral muscular artery (31), with mycotic aneurysms
comprising 58% of these lesions (32). Of these, most patients are <50 years of
age. Sixty-three percent of reported SMA aneurysms occur in men (33).
Etiology
Aneurysms of the SMA are usually mycotic, with subacute bacterial endocarditis found in many
cases. A variety of pathogens, namely, Streptococcal and Staphylococcal species, are
frequently isolated in these patients. Complications from pancreatitis can also affect the SMA
much the same way that it does the splenic artery (Fig. 15-8). Dissecting aneurysms
associated with medial defects are rare but affect this vessel more than any other visceral
artery (34,35). Chronic atherosclerotic disease, as a primary or secondary event, is evident in
approximately 20% of reported superior mesenteric artery aneurysms. Aneurysm formation
from trauma is considered rare (18).
FIGURE 15-8. A: Pseudoaneurysm as a complication of pancreatitis. B: Selective arterial

injection confirming the location of the pseudoaneurysm off a branch of the SMA. C:
Arteriogram using a microcatheter placed adjacent to the pseudoaneurysm. D: Arteriogram
after placement of one Hydrocoil (Microvention, Inc.; Aliso Viejo, CA) demonstrating
absence of flow into the pseudoaneurysm. E: Unsubstracted arteriogram again
demonstrates absence of pseudoaneurysm flow postembolization.
Diagnosis
Most SMA aneurysms are symptomatic, which differentiates them from other visceral
aneurysms. Typically patients present with moderate to severe abdominal pain that is usually
progressive (36). In certain instances it may be difficult to distinguish symptomatology due to
mesenteric ischemia, otherwise known
as intestinal angina, from that due to aneurysmal expansion. A tender pulsatile abdominal mass
that is not rigidly fixed has been discovered in nearly half of these patients (18). Chronic
aneurysmal disease from atherosclerosis can often contain mural thrombus, which can also
cause symptoms of chronic embolization or may lead to thrombosis of the artery resulting in
acute mesenteric ischemia (28). CTA is the noninvasive imaging technique of choice to confirm
diagnosis. Ultrasound is considered less sensitive given its inherent limitation in evaluating
structures deep to bowel. Arteriography should be performed only when intervention is planned.
Treatment
The diagnosis of a superior mesenteric aneurysm indicates treatment even in asymptomatic
patients since spontaneous rupture is frequent and mortality approaches 50% for the SMA (18).
Surgery is the preferred treatment option but is complicated since inflammation and infection
are common features of these aneurysms. Exposure is by either a transmesenteric or a
retroperitoneal route after medial visceral rotation. Because most SMA aneurysms are located
proximally, simple ligation is possible since collaterals from the celiac through the inferior
pancreaticoduodenal artery are usually present. Revascularization using an interposition graft or
aorto-SMA bypass is also an option.
In the mesenteric arteries, occlusion of terminal branches can have catastrophic consequences.
Therefore most investigators are hesitant to use percutaneous techniques in these vessels so
very few interventional treatments have been described (5). Unless coils can be safely packed
into a saccular aneurysm, stent-grafting to preserve flow in the SMA is indicated. When
deploying the stent, care must be taken not to cover any essential collaterals which may have
formed.
CONCLUSION
Visceral artery aneurysms are uncommon, life-threatening lesions with no universally accepted
standard of care. What is clear, however, is that they warrant management often in the form of
endovascular intervention. Despite the absence of large series with long-term follow-up, it is
generally understood that treatment techniques endovascular are safe and effective.
An understanding of the patient's clinical situation as well as thorough characterization of the
lesion itself is paramount to treatment success. For the time being, standard embolization
remains the first- line treatment of choice, with stent-grafts and thrombin being options in select
cases. As stent-grafts become more cost-effective, with an improved profile and flexibility, they
will likely surpass embolization due to their inherent advantages.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 16 - Endovascular
Management of Nonspecific Aorto-arteritis
Chapter 16
Endovascular Management of Nonspecific Aorto-
arteritis
Sanjiv Sharma
Priya Jagia
Nonspecific aorto-arteritis, also known as Takayasu arteritis, is a chronic and progressive
panarteritis of an unknown cause that commonly affects the aorta, its major branches, and the
pulmonary arteries (1, 2, 3, 4, 5, 6). It results in stenoses, occlusions, dilatations, or formation
of aneurysms in the involved blood vessels (1, 2, 3, 4). Vessel inflammation results in thickening
of the wall, fibrosis, stenosis, and thrombus formation and produces ischemic symptoms in the
involved territories (Fig. 16-1). The inflammation can also destroy the arterial media and lead to
aneurysm formation (Fig. 16-2). We previously demonstrated such lesions during intravascular
ultrasound evaluation of a group of patients with this disease (7).
Even though the disease is more common in parts of Northeast Asia, China, Thailand, the
Philippines, and India, it has a worldwide distribution (1, 2, 3, 4, 5, 6, 7, 8, 9). There is an
overall female preponderance, although the female-to-male ratio seems to decline from eastern
Asia toward the West (10). The disease commonly occurs in the second and third decades of
life. In an earlier study, we observed that as many as 31% of patients from India were <16
years of age (2,11).
Etiology
The etiopathogenesis of this disease is poorly understood even though it was first described
more than a century ago (12). Different etiologies such as syphilis, giant cell arteritis,
malignancy, infection, rheumatic fever, autoimmune disease, and congenital vascular anomalies
have been suggested. However, none of these have been convincingly shown to be a causative
factor.
Many studies from India and Japan have reported hypersensitivity to Mycobacterium
tuberculosis as a possible cause. Lupi-Herrera et al. (13) have shown evidence of previous
tuberculosis in 48% of patients from Japan. Sen et al. (14) reported from India that 71% of
their patients showed evidence of tuberculosis. Pantell and Goodman (15) reviewed the
literature from 1961 and 1981 and found positive tests for tuberculosis in 73% of 100% of
cases. They found active tuberculosis in 0.26% to 4.2% of patients and suggested that
tuberculosis was more likely to be present in patients with Takayasu arteritis. It has been
postulated that this disease is caused by an immune response after the human host is exposed
to M. tuberculosis bacterial heat shock protein (16). Heat shock protein is a major immunogenic
component of M. tuberculosis and the expression of this protein is strongly induced in aortic
tissue by the cytotoxicity of infiltrating lymphocytes. Aggarwal et al. (16) reported high levels of
antibodies to tubercular antigens, especially heat shock protein, thus suggesting a role of M.
tuberculosis in the pathogenesis of Takayasu arteritis.
Sagar et al. (17) found significant blast transformation in response to purified human aortic
antigen, suggesting an autoimmune mechanism. Purified protein derivative also evoked variable
responses, suggesting that though autoimmunity may be responsible, the antigen might not
necessarily be M. tuberculosis. Furthermore, direct involvement of M. tuberculosis is not likely
since we have consistently observed that the tubercular vascular lesions are discrete, with
erosion of the wall and formation of false or true aneurysms. Dissection and rupture of
aneurysms, which are uncommon with Takayasu arteritis, are more common with tuberculous
aortitis. Stenotic involvement of the aorta and its large branches, characteristic of Takayasu
arteritis, is not a feature of tuberculous aortitis. In addition, most of the studies regarding the
link of this disease to tuberculosis are from countries where tuberculosis was highly prevalent at
that time. Perhaps the only exception is the fact that Japan, despite a reduced incidence of
tuberculosis, still reports a substantial number of cases of Takayasu arteritis. More recently,
viral infection is being investigated as a trigger of vasculitis (17).
Judge (18) noted high levels of -globulins, increased erythrocyte sedimentation rate (ESR),
leukocytosis, arthralgia, and anti-aorta antibodies in patients with Takayasu arteritis. The role of
autoimmunity is further corroborated by the association of this disease with other clinical
conditions such as systemic lupus erythematosus, Still's disease, diabetes, and thyrotoxicosis.
Defective T cell regulation, with an increased CD4/CD8 ratio in peripheral lymphocytes, and
increased B lymphocytes, has also been reported in some patients with Takayasu arteritis (17).
The most probable hypothesis suggests that cell-mediated immunity may have a role in its
etiopathogenesis while humoral autoimmune mechanisms may not be important pathways in the
initiation of this disease (19,20).
The reports of familial incidence of Takayasu arteritis may point to a genetic origin. In Japan, 16
families with familial Takayasu arteritis have been reported (21). In India, Mehra et al. (22)
studied 104 patients and suggested an association of this disease with human immune
response genes, namely, HLA-B5 as well as its serological subtypes, B51 and B52. In HLA-
B52-positive patients, aortic regurgitation, ischemic heart disease, and pulmonary infarction are
more common. Renal artery stenosis is reported more frequently in HLA-B39-positive patients.
The HLA association is thought by some to strengthen the argument in favor of an autoimmune
pathogenesis. However, no specific autoantigens have yet been identified, and for any adaptive
immune response to occur, whether against exogenous or endogenous antigen, presentation of
antigen to T cells in the context of the major histocompatibility complex is central.
The predominant involvement of females has prompted investigators to study the role of sex
hormones. Urinary estrogens were elevated in 80% of patients (16 of 20 patients) compared to
healthy controls in one study (23). It is possible that this
disease starts in a genetically predisposed individual with a specific hormonal milieu, who, on
later exposure to specific unidentified antigens (such as tuberculosis), develops an immune
response affecting the vessels.
FIGURE 16-1. A: A 20-yr old female with absent upper limb pulses and hypertension: intra-
arterial DSA (IADSA) of aortic arch in LAO view shows occlusion of all arch vessels. Right
common carotid artery and left vertebral artery are filling via collaterals. There is also tight
thoracic aortic stenosis. B: A 17-yr old female with hypertension: IADSA in AP view shows
tight suprarenal and perirenal aortic stenosis. Bilateral ostial mild renal artery stenoses are
also seen. Findings are consistent with nonspecific aorto-arteritis.
FIGURE 16-2. A 19-year-old women with hypertension: intra-arterial DSA in AP view
shows multiple saccular aneurysms in perirenal and infrarenal aorta. Tight left renal artery
stenosis is also shown. Findings show a different manifestation of nonspecific aorto-
arteritis.
Diagnosis
The disease is characterized by an initial phase marked by nonspecific constitutional symptoms
and signs. Presence of active vascular inflammation may include aggravation of symptoms and
signs of active disease, aggravation or appearance of new angiographic lesions, or presence of
abnormal serological tests showing increased levels of acute-phase reactants, such as ESR, C-
reactive protein, or anti-streptolysin O titers. The above-mentioned reactants may be present
alone or in combination. The presence of active disease has therapeutic implications, as the
outcome of revascularization is adversely affected by it. Hence, it is important to identify clinical
remission before advocating endovascular or surgical revascularization to treat the
complications of vascular inflammation.
Various methods have been used to identify active disease. The constitutional symptoms
include fever, anorexia, arthralgia, limb ischemia, hypertension, and raised ESR. These acute-
phase symptoms may be present in half of patients. The rest of the patients present with
advanced obstructive changes with no symptoms of acute phase. Surgical biopsy specimens
from patients with clinically inactive disease showed histologically active disease in as many as
44% (24). Furthermore, one study concluded that no known serological test was able to
supplant vascular histopathology in determining disease activity (22). Similarly, 61% patients
with remitting disease showed new
lesions on angiography, thus emphasizing the need for more reliable accurate markers for
disease activity.
The National Institutes of Health (Bethesda, Maryland) has described active disease as new
onset or progression of at least two of the following features (25):
1. signs and symptoms of vasculitis or ischemia (include claudication, feeble or absent pulses,
differential blood pressure in extremities, bruits, and carotidynia);
2. an elevated ESR;
3. angiographic abnormalities; and
4. systemic symptoms such as fever, polyarthralgia, and polymyalgia.
A study by the International Network for the Study of the Systemic Vasculitides (INSSYS)
enlisted 29 patients with Takayasu arteritis and 26 healthy controls. The activity was assessed
based on Birmingham Vasculitis Activity scores (26). Serological tests including ESR, C-
reactive protein, tissue factor, Von Willebrand factor, thrombomodulin, tissue plasminogen
activator, ICAM-I, VCAM-I, E-selectin, and PECAM-I were performed on all the patients but
could not reliably differentiate between healthy volunteers and patients with Takayasu arteritis.
The clinical and biochemical markers remain poor predictors of clinical activity.
FIGURE 16-3. Ultrasound examination of right common carotid artery in A: longitudinal and
B: transverse sections showing markedly increased intimal-medial thickness. C: Contrast-
enhanced CT in another patient shows wall thickening in thoracic aorta with mural
enhancement. These findings suggest an active inflammatory process in aorto-arteritis.
Imaging
Recently, noninvasive imaging modalities, such as duplex sonography, computed tomography
(CT) and magnetic resonance (MR) imaging (MRI), have also been used for the detection of
active disease. High-resolution B-mode ultrasound can detect intimal-medial thickness with or
without obstructive stenosis (Figs. 16-3a and b). An increased intimal-medial thickness may
suggest the presence of active disease (27). Maeda et al. (28) reported circumferential arterial
wall thickening of the common carotid arteries, which may or may not be bilateral. MRI and CT
have been used to demonstrate the arterial wall thickness. Whereas unenhanced CT scans
may show a
high-density wall of variable thickness in the aorta or its branches along with calcification, if
present, helical CT angiography may show enhancement of the thickened aortic wall (Fig. 16-
3c) in patients with active inflammation (29). MRI shows the subtle thickening in early cases
and T2-weighted images may show bright signal due to edema in and around the inflamed
vessel (Fig. 16-4). During the acute phase, enhancement of the aortic wall and peri-adventitial
soft tissues can also be observed (30). It has been suggested that contrast-enhanced MRI may
be more sensitive than the serological markers of clinical activity in this disease, but overall,
these MR criteria are not highly sensitive but they are highly specific of disease activity (30).
Those authors also observed that the sensitivity of T2-weighted imaging in the detection of
active disease seemed to be inferior to that of contrast-enhanced T1-weighted imaging. Aortic
wall thickness by itself may also reflect activity of the disease (31). In this study, most patients
with inactive disease had a wall thickness of <4 mm and most of them with acute or chronic
active disease had a wall thickness of 5-7 mm.
FIGURE 16-4. Axial MRI T2-weighted image shows a thickened juxtadiaphragmatic aortic
wall with bright signalconsistent with edema and inflammation.
Intravascular ultrasound techniques have shown thickening of the vessel wall and altered
echogenicity of the media, adventitia, and peri-arterial tissues in patients with active disease
(Fig. 16-5) (7). Furthermore, an increased incidence of myocarditis has been reported in
patients with active disease, suggesting the presence of myocarditis as an indicator of active
disease (32). Overall, serological markers along with the above imaging techniques or
endomyocardial biopsy may be useful in assessing the activity of the disease.
The morphological pattern of involvement in Takayasu arteritis shows racial and geographic
differences (6). In Japan, thoracic aortic involvement is more common and neck vessels are
most often involved (3). In most other Asian countries, the abdominal aorta is most frequently
affected, with the renal and subclavian arteries being the most commonly involved branches (2).
Although pulmonary artery involvement is common in most studies, among Indian patients it is
less frequent. In a prospective study, we found pulmonary arterial involvement in 14.9% of
patients (4). In most studies that have evaluated the angiographic morphology, obstructive
lesions predominate (1,2,3,8). When present, dilative and aneurysmal lesions also show distinct
geographic predilections. There is a disproportionately high incidence of these lesions in the
Philippines, Thailand, Israel, Japan, and western India (9,33). Fusiform aneurysms probably
have a genetic predilection because they are seen in a distinct racial subset. In this regard, it is
worth mentioning that the phenotype frequencies of various loci of HLA-A and HLA-B antigens
show significant differences between patients from Japan and those from India. Such
differences may also account for different angiographic morphologies of the disease in different
locations (8).
FIGURE 16-5. Intravascular ultrasound of thoracic aorta in a 14-year-old boy with

hypertension shows thickened media and adventitia with hyperechoic pattern consistent
with active inflammation.
The diagnosis is based on distinct clinical and angiographic features that include the presence
of (1) symptoms caused by ischemia of the CNS, upper extremities, or kidneys; (2) fever,
absent or decreased pulses, bruits, and funduscopic findings; (3) increased ESR and presence
of C-reactive protein; and (4) angiographic findings including a spectrum of changes ranging
from minimal intimal irregularity to typical rattail narrowing, complete obstruction, or aneurysm
formation in the aorta or its branches (34, 35, 36). Involvement of the aorta and the medium-
sized branches is considered essential for diagnosis. Conditions such as Buerger's disease,
Kawasaki's disease, syphilis, Beh's disease, tuberculosis, giant cell arteritis, collagen vascular
disease, developmental anomalies (such as coarctation of the aorta, Marfan's syndrome),
atherosclerosis, thromboembolism, and congenital vascular malformation should be excluded.
CLINICAL MANAGEMENT
The goals of therapy include control of clinical activity by pharmacologic treatment with steroids
and/or immunosuppressive therapy, restoration of blood flow to the stenosed vessel by surgical
or endovascular techniques, pharmacologic control of blood pressure (BP), and supportive
management.
Renovascular hypertension (RVH) is perhaps the most common form of treatable clinical
presentation of this disease. This is usually caused by obstructing lesions involving the aorta
and the renal arteries (36,37). Takayasu arteritis is a common cause of RVH in India. Chugh et
al. (5) studied the causes of RVH in India and reported that nonspecific aorto-arteritis was
responsible for 61%, fibromuscular dysplasia for 28%, and atherosclerosis for 8% of patients.
Some form of revascularization is necessary to relieve ischemia secondary to a
hemodynamically significant stenosis. The complexity of pathological changes in the wall of the
aorta and widespread nature of involvement make surgical revascularization difficult. There is
also a high prevalence of graft occlusion or aneurysm formation at the treatment site (38, 39,
40). For these reasons, nonsurgical revascularization techniques have been used increasingly in
the treatment of this disease (36,37,41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52).
ENDOVASCULAR MANAGEMENT
Patients are treated by endovascular techniques if they have hypertension uncontrolled by
optimized drug therapy, angiographic evidence of at least 70% stenosis in the renal artery,
peripheral artery, or aorta with a pressure gradient of >20 mm Hg, and a normal ESR. Patients
with an elevated ESR and/or a positive C-reactive protein test are considered to have active
arteritis and are not accepted for this treatment.
Antihypertensive medication is stopped 24 hr before angioplasty, except for the use of short-
acting drugs such as nifedipine, 5-10 mg administered sublingually, if the BP is >170/110 mm
Hg. The patients are treated with aspirin (175-330 mg) daily for 3 days before angioplasty, and
this treatment is continued for 6 months after treatment. Heparin (100 IU/kg body weight) is
given intravenously during the procedure and is not reversed afterward. BP medication is
withheld for 24 hours after the procedure, except for the use of short-acting drugs if the BP is
>160/100 mm Hg.
Prior to the procedure, informed, written consent is obtained. The femoral route is preferred. In
difficult situations, such as an acute downward angulation of the involved artery or
nonavailability of the femoral route due to concomitant obstructive disease, a brachial approach
is used. At the beginning of the procedure, an arterial sheath is placed in the femoral artery in
each groin by percutaneous route. For PTRA, a pigtail catheter is positioned in the abdominal
aorta above the origin of the renal arteries for continuous pressure measurement and
diagnostic digital subtraction angiography (DSA). The diseased renal artery is selectively
catheterized through the other arterial sheath and transstenotic pressure gradient is measured.
Then, the angiographic catheter is exchanged for an appropriate-sized balloon catheter using
standard over-the-wire techniques. The diameter of the involved vessel is measured and a
balloon of the same size is used for angioplasty. Three to five inflations, for up to 45 seconds
each, are performed until the balloon waist is no longer present or has decreased
substantially. The result is assessed by a check angiogram at the end of the procedure (Fig.
16-6). PTRA can also be performed by positioning a preshaped guiding catheter at the ostium
of the involved renal artery for coaxial introduction of guide wires and catheters. The lesion is
then crossed and dilated using an over-the-wire or monorail technique. In lesions where a
branch vessel originates or is involved in the stenosis, a kissing balloon technique is employed
using a coaxial approach. Immediately after the procedure, the transstenotic pressure gradient
is measured and an angiogram is obtained to assess the adequacy of angioplasty. We avoid
the risk of arterial rupture by not using oversized balloons in patients with a mild residual
stenosis or minimal transstenotic pressure.
If there is an obstructive dissection or a recurrent ostial stenosis, stent placement is
considered. For planned stenting, additional pretreatment with clopidogrel (75 mg once daily) is
desirable, beginning 3 days before the angioplasty. Alternatively, a single dose of 300 mg of
clopidogrel is given, in patients in whom a bail-out stenting is performed. Subsequently, oral
clopidogrel (75 mg daily) is continued for 6 weeks after the procedure. During the procedure, a
preshaped renal guiding catheter is positioned at the ostium of the diseased renal artery over
an exchange guide wire placed in a secure distal location. The selection of the diameter and
length of the stent are based on the angiographic morphology of the involved artery. It is
advisable to give sublingual nifedipine (5-10 mg) or an intra-arterial bolus of nitroglycerine (100-
200 g) in the renal artery before stent placement. The stent is positioned across the lesion
and released by inflating the balloon at the desired inflation pressure for up to 30 seconds.
Various stent designs are available, but balloon-mounted stents are preferred. A check
angiogram is obtained at the end of the procedure to assess the adequacy of stent release
(Fig. 16-7). Intravascular ultrasound is useful in defining the end point of intervention.
Angioplasty or stent placement in the aorta and the carotid and subclavian arteries is performed
by a similar technique.
It has traditionally been reported that nonspecific aortoarteritis involves all layers of the vessel
wall (1,3). Its histopathology is characterized by inflammatory changes, with marked tissue
destruction and connective tissue proliferation initiated at the junction of the media and
adventitia or the outer layer of the media. There is an endo-arteritis obliterans or onion skin-
type fibrosis in the vasa vasorum. Thickening of the intima results from an increase in the
ground substance and proliferation of connective tissue (1,3,34,35). Underlying chronic
inflammation, extensive peri-arterial fibrosis, thickening, and adhesions combine to produce
tough, noncompliant, and rigid vessel walls. In view of these features, the stenotic lesions resist
prolonged, repeated mechanical distension before responding to balloon dilatation. In addition,
the risk of arterial tear or rupture is high if the vessel is overdistended during angioplasty. We
have observed that predilatation by a Teflon catheter is required in most patients before the
balloon catheter can be positioned across the stenosis. Multiple, prolonged balloon inflations
are usually necessary to obtain a substantial decrease in the stenosis. Most patients
experience an intense, transient backache during balloon inflation, often accompanied by a
transient fall in BP. This subsides soon after balloon deflation. If this finding persists, an
obstructive dissection should be suspected.
Angioplasty is considered technically successful if (1) the aortic or renal artery lumen after
angioplasty has <30% residual stenosis, (2) the arterial lumen is at least 50% larger than its
pretreatment diameter, and (3) the pressure gradient is <20 mm Hg and has decreased at least
15 mm Hg from the pretreatment gradient. The clinical results of renal angioplasty are judged
as follows: (1) cure (normal BP after the procedure without antihypertensive drug therapy), (2)
improved (at least 15% reduction in diastolic pressure or a diastolic pressure <90 mm Hg with
the patient taking less antihypertensive medication than before the procedure), and (3) failed
(no change in BP after the procedure) (52,53). All patients cured or improved are considered to
have benefited from angioplasty. Follow-up is performed by BP and medication evaluation at 1
day, 1 week, and 4 to 6 weeks after treatment and then at 6-monthly intervals. Follow-up
angiograms are performed in patients with recurrence of hypertension and in whom
contralateral nephrectomy, of a poorly or nonfunctioning kidney causing residual hypertension,
is planned. Angioplasty is repeated if restenosis is detected.
Results for Renal Lesions

A total of 276 patients with renovascular hypertension caused by this disease have been
treated by interventional radiological techniques over a 14-year period (36,47,50). These
included 264 renal arteries in 193 patients and 88 aortas in 83 patients. Among the renal
arteries, technical success was achieved
in 96% procedures. The stenosis decreased from 87% 6% (range, 70% to 100%) to 11%
11% (range, 0% to 40%, and the pressure gradient fell from 95 22 (range, 30-140) to 9 8
(range, 0-30) mm Hg (p < 0.01). Clinical benefit was seen in 91% of patients and included cure
in 32% and an improvement in 68% of them. The drug requirement for control of hypertension
decreased from 3.9 0.5 (range, 2-5) to 1.1 0.9 (range, 0-3), the systolic BP improved from
181 16 (range, 150-220) to 136 25 (range, 110-210) mm Hg, and the diastolic BP fell from
115 10 (range, 90-126) to 86 16 (range, 60-116) mm Hg (p <0.01). The complications
included a groin hematoma in eight, transient renal artery spasm in seven, and renal vein injury
requiring surgery in one patient. In addition, an obstructive dissection was seen in two patients,
both of whom were successfully treated by stent placement. The follow-up period ranged from
3 to 104 (49 22) months. Remodeling at the PTRA site with further angiographic improvement
was seen in most patients who underwent repeat angiography. Restenosis was seen in 17%
lesions, all of which were successfully retreated. The cumulative 5-year patency rate was 67%.
FIGURE 16-6. A 16-year-old girl with hypertension. A: Intra-arterial DSA shows perirenal
aortic stenosis with tight ostial and proximal right renal artery stenosis. The left renal artery
is occluded. B: A renal guiding catheter is positioned at the right renal artery ostium, with
an over-the-wire balloon inflated across the ostial stenosis. C: Check angiogram after
PTRA shows a substantial improvement in the arterial lumen with a small, capped,
nonobstructive dissection.
Many authors have reported their results for renal angioplasty (PTRA) (34,36,42, 43, 44, 45,
46, 47, 48, 49, 50). Most of them concern a single case or a small group of patients. Dong et
al. (45) reported 30 patients. Of these, the lesion was associated with nonspecific arteritis in
22 patients. The procedure was successful in treating hypertension in 86% of them.
Complications were encountered in seven patients (excessive bleeding in three,
pseudoaneurysm needing surgery in one, occlusion of the renal artery in two, and dissection of
the renal artery in one). Kumar et al. (46) reported the results in nine patients, with clinical
success in 55%. Procedure-related complications occurred in 33% of cases. Tyagi et al. (52)
performed renal angioplasty in 35 patients. Of these, nonspecific arteritis was the cause in 31
cases. Clinical benefit was seen in 92% of cases. Complications were not reported.
We have observed that the use of an angled hydrophilic guide wire reduces the risk of
complications related to vessel
spasm and perforation. The overall restenosis rate after a technically and clinically successful
PTRA in the presence of clinically inactive disease is low. In our study, the restenosis was seen
in 17% of patients (36,47,49). We have also observed that ostial stenosis, residual stenosis of
>30%, and residual pressure gradient of > 10 mm Hg after PTRA, coexisting
juxtadiaphragmatic aortic stenosis, and reactivation of the underlying disease predispose to
restenosis. In this clinical setting, even though an ostial stenosis is more likely to recur, the
restenosis is usually postostial and shows a good long-term result following successful repeat
PTRA. Overall, PTRA is safe and effective in treating hypertension, with encouraging follow-up
results and low complication rate. The underlying disease produces specific technical problems
but the technique can be suitably modified to successfully overcome them in most cases. We
recommend the use of this treatment method in suitable cases.
FIGURE 16-7. A 20-year-old hypertensive man. A: Tight ostial right renal artery stenosis
on intra-arterial DSA (IADSA) image. B: IADSA after stent placement shows elimination of
the stenosis and smooth arterial outline.
Results for Aortic Lesions

Percutaneous transluminal angioplasty (PTA) for the treatment of aortic stenosis in the
presence of nonspecific aortitis has been infrequently reported (37,45,51). The angiographic
morphology of 140 aortic stenoses has been correlated with the outcome of balloon
angioplasty. Patients with short-segment (<4-cmlong) stenosis show better overall results than
those with long-segment (>4-cm-long) stenosis. The angiographic features, including
eccentricity of the stenosis and presence of diffuse adjacent disease, location of the stenosis in
the juxtadiaphragmatic segment of the aorta, and presence of calcification adversely affect the
outcome of PTA; most of these patients develop large intimal flaps. Such patients should be
electively treated by stent placement. Stents have also been used as a bail-out measure in
salvaging an obstructive dissection (51,54). Our results show that stents provide immediate
relief of symptomatic obstructive dissection and are also useful in the treatment of recurrent
stenosis after successful angioplasty (54). We do not advocate elective use of stents due to
the young age of the patients, cost involved, and lack of knowledge about the long-term
behavior of stents in the aorta at a growing age, except in situations mentioned above.
Until recently, it was felt that this disease was characterized by skip-lesions, with intermediate
regions spared of involvement. The findings of recent studies, using cross-sectional imaging
techniques, suggest that nonspecific aortitis involves a continuous length of the aorta, producing
mural and luminal changes in some areas and only mural changes in the intervening segments
(41,54). This observation has important therapeutic implications. The site of surgical
reconstruction or balloon positioning in PTA is based on the demonstration of angiographically
normal adjacent segments. The results of cross-sectional imaging suggest that there are
extensive wall changes even in angiographically normal areas. The unpredictable outcome of
PTA and surgical revascularization, in our opinion, is caused by the placement of a bypass graft
or the balloon catheter within the diseased segments and not from normal to normal aortic
segment. In this regard, intravascular ultrasound may be useful in guiding the interventional
procedures. Overall, aortic PTA has specific technical problems but has a high technical and
clinical success rate. The complication rate is low. Late remodeling occurs in most patients and
is responsible for delayed clinical benefit despite poor technical success in some patients.
Among aortic lesions, the stenosis involved the descending thoracic aorta in 56% and the
abdominal aorta in 44% patients (49,54). Technical success was seen in 84% and clinical
success in 89% of patients. The stenosis decreased from 81% 7% to 19% 18%, the
pressure gradient fell from 76 19 to 26 11 mm Hg, the BP fell from 185 20/112 12 to
146 12/90 7 mm Hg, and the drug requirement fell from 4 1 to 1 1 (p <0.001 for all).
Localized, nonobstructing flaps at the PTA site were seen in approximately half of patients
(Figs. 16-8 and 16-9). Eleven patients developed an obstructive dissection. Among them, eight
patients were successfully treated by stent placement (Fig. 16-10), two were managed
conservatively, and one patient underwent surgery. The followup period ranged from 3 to 97
(37 17) months. Two patients developed a pseudoaneurysm at the PTA site during follow-up.
Remodeling at the angioplasty site with further angiographic improvement was seen in most
patients. Some patients showed a delayed clinical benefit, despite a poor technical result,
probably due to late remodeling. The restenosis rate was 5%. One patient had recurrent
stenosis despite three successful PTAs within a period of 14 months and was treated by stent
placement. The cumulative 5-year patency rate was 71%.
FIGURE 16-8. A 20-year-old female with claudication and uncontrolled hypertension. A:
Intra-arterial DSA (IADSA) showing occluded left renal artery, tight ostial and proximal right
renal artery stenosis, occluded SMA, and tight infrarenal aortic stenosis extending to
involve proximal left common iliac artery. B: Check IADSA after PTA of right renal artery,
infrarenal aorta, and left common iliac artery shows substantial improvement in arterial
lumen and no obvious dissection flap.
FIGURE 16-9. A 24-year-old female with claudication and hypertension. A: Intra-arterial
DSA (IADSA) shows a tight juxtadiaphragmatic aortic stenosis. B: Post-PTA IADSA shows
a substantial improvement in the aortic caliber with mild residual stenosis.
FIGURE 16-10. A 26-year-old female with uncontrolled hypertension. A: Intra-arterial DSA

(IADSA) in AP view shows a significant eccentric thoracic aortic stenosis with poststenotic
dilatation. B: Check IADSA after PTA shows an obstructive dissection flap with no
improvement in pressure gradient. C: Final IA-DSA after stent placement shows a smooth
outline and improvement in aortic caliber. The transstenotic gradient was reduced from 80
to 6 mm Hg.
The outcomes of endovascular interventions in the supraaortic branches are less rewarding.
Due to the presence of diffuse lesions and increased wall thickening, the stenosis in the carotid
and subclavian arteries responds less well to balloon angioplasty. We treat these lesions less
often, because even though they are commonly present, they are largely asymptomatic. When
symptomatic, most lesions are very long and not well suited for endovascular management.
Among those with suitable angiographic morphology, the luminal stenosis and transstenotic
pressure gradients are difficult to abolish, as the stenosis often does not respond to multiple
high-pressure balloon dilatations. Even after initial successful angioplasty, the restenosis rate is
high.
CONCLUSION
Overall, interventional radiological techniques, including angioplasty and stenting, are useful in
the management of nonspecific aorto-arteritis. Judicious case selection and a proper
understanding of the technical complexity of the procedures are essential for their optimal
utilization in this clinical setting. Disease activity should be assessed before accepting patients
for treatment by endovascular methods. Further research is needed to identify reliable markers
of disease activity.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 17 - Renal Angioplasty and
Stenting
Chapter 17
Renal Angioplasty and Stenting
Thomas A Sos
David W. Trost
Renal artery stenosis (RAS), hypertension, and renal insufficiency (RI) are each frequently
present, especially in the elderly population. RAS is often present without any clinical signs or
symptoms, and even when hypertension or RI is also present, they may be coincidental rather
than causally related. However, when RAS is hemodynamically or physiologically significant, it is
one of the few potentially reversible causes of RI (1, 2, 3) and hypertension (Fig. 17-1) (4).
The challenge for physicians is to identify patients with RAS who would benefit from renal
revascularization, whether by interventional techniques or open surgery. In order to do so, RAS
must first be clinically suspected and anatomically identified. Its physiological significance and
causal relationship to hypertension or RI must be documented. The risk and benefit of
alternative medical and invasive therapies must be compared to each other and to the natural
history of the disease.
This chapter discusses the identification and evaluation of these patients, treatment strategies,
and detailed discussion of the techniques of treatment with angioplasty and stents and their
clinical outcome.
ETIOLOGY AND PATHOLOGY OF RENAL ARTERY STENOSIS

Atheroma
Atherosclerotic RAS (ARAS) is the etiology of ~90% of RAS (Fig. 17-2). Most ARAS occurs at
the ostium of the renal artery and consists of atheroma of the aortic wall that engulfs the orifice
of the renal artery and extends into the proximal renal artery (5). Some proximal ARAS lesions
that occur within the first centimeter of the renal artery appear to be separate from the ostium
on arteriography but behave as ostial lesions do when angioplasty is attempted. Focal ARAS
>1 cm distal to the renal artery origin is less frequent.
Solitary, focal proximal branch disease is extremely rare in ARAS, and although it can produce
renal vascular hypertension (RVH), it does not produce RI. Multiple small-branch RAS is
present only in severe diabetics or end-stage renal disease (ESRD) and is not amenable to
interventional therapy.
Fibromuscular Dysplasia and Arteridites
Various forms of fibromuscular dysplasia (FMD), the most common being the medial form
(string of beads appearance) (Fig. 17-3), along with rarer arteridites including
neurofibromatosis, Takayasu arteritis, and midaortic syndrome account for the other 10% of
RAS. FMD usually occurs in the mid to distal third of the renal artery and frequently extends
into proximal branches. All these conditions can cause severe stenosis, though occlusion in
FMD is rare. RVH in FMD is common, but RI is unusual.
Renal Artery Stenosis in the Pediatric Age Group

RAS in infants and young children is a special, difficult-toclassify group of diseases that usually
manifest as focal branch stenosis; the typical beady medial form of fibroplasia affecting longer
segments of the artery is rarely seen. The stenoses may occur in only a branch in most cases;
in the rest, in combination with main RAS or limited to the main renal artery (6,7). The
strategies for anatomic diagnosis in the pediatric age group are therefore different from those
for adult FMD and ARAS; detection of branch disease in these often small branches is critical.
Transplant Renal Artery Stenosis

Most transplant RASs are due to neointimal hyperplasia, accelerated atherosclerosis, and
clamp or other iatrogenic injury, usually in the peri-anastomotic area, cadaver transplants with
long ischemic times (8), cytomegalovirus infection (9), rejection or other autoimmune
mechanisms (10), and kinking due to malposition of the allograft in the pelvis (8,11,12). Until
approximately 10 years ago transplant renal arteries had been anastomosed end to end to the
hypogastric arteries, however, recently almost all are anastomosed end to side to the external
iliac arteries. If transplant RAS is clinically suspected, but not demonstrated by imaging,
stenosis of the inflow aorto-iliac circulation should be looked for.
Pathophysiology
Hemodynamically significant RAS produces RVH via the renin, angiotensin, aldosterone system
(13). The macula densa in the juxtaglomerular apparatus of an ischemic kidney liberates rennin,
which acts to change angiotensinogen to angiotensin I, which in turn is transformed by
angiotensin converting enzyme in the lung into angiotensin II. Angiotensin II is a powerful
vasoconstrictor that produces systemic hypertension and also liberates aldosterone, which
produces retention of sodium and water. In unilateral RAS the healthy contralateral kidney
excretes the retained fluid and the hypertension remains renin dependent. In significant bilateral
RAS, in RAS in a solitary kidney, or in unilateral RAS with contralateral parenchymal damage
such as hypertensive nephropathy, the fluid is retained; this eventually turns off renin production
and the hypertension becomes volume or fluid dependent. This explains why patients with
severe bilateral RAS are often precariously balanced
between renal failure and congestive heart failure, depending on their state of hydration, and
also why many of the physiologically based noninvasive tests to identify significant RAS are
unreliable in the presence of bilateral RAS and RI. High levels of angiotensin II also stimulate
cellular hypertrophy and proliferation of vascular smooth muscle cells, promote vascular and left
ventricular hypertrophy (14), accelerate atherosclerosis (15), and are associated with
progressive glomerular sclerosis independent of the level of hypertension (16). Physiologically
significant RAS also has direct effects on sympathetic nerve activity, nitric oxide production, and
intrarenal prostaglandin concentration (17,18). When patients with ARAS progress to ESRD
their mortality is significantly higher than that of the general dialysis population (19). All of these
hemodynamic and humoral mechanisms contribute to major adverse cardiovascular events
(MACEs) such as death, dialysis, myocardial infarction, and stroke.
FIGURE 17-1. The complex relationship of renal artery stenosis, hypertension, and renal
insufficiency and their clinical presentation. (After Safian RD, Textor SC. Renal artery
stenosis. N Engl J Med. 2001;344:431-442, with permission.)
FIGURE 17-2. Ostial (curved arrow) and proximal (straight arrow) ARAS. These usually
show immediate elastic recoil following angioplasty and require stents for long-term
patency. Nonostial (notched arrowhead) atheromatous stenoses more than >1 cm distal
from the ostium are less frequent but usually respond well to angioplasty alone.
FIGURE 17-3. The various forms of fibromuscular dysplasia (FMD) and their frequency.
The medial fibroplasia subclassification of medial FMD (string of beads) is most common.
(Reproduced with permission from Trost DW, Sos TA, Pickering TG. Percutaneous
transluminal angioplasty and stenting for renal artery stenosis and renal artery
thrombolysis. In: Pollack H, McClennan B, Dyer SA, et al., eds. Clinical Urography. 2nd
ed. Philadelphia: Saunders; 2000.)
PREVALENCE
The prevalence of ARAS in the general population in the United States is less well documented
than that of coronary heart disease. While it is now generally accepted that atherosclerosis is a
systemic disease that affects all vascular territories, there are differences in the clinically
symptomatic incidence and therefore the detection rates of symptomatic and asymptomatic
disease in different vascular systems. The overall incidence of RAS
in hypertensives is usually quoted as being 5% (20). Since 20% to 30% of the 300 million U.S.
population (21) is hypertensive, 6 million to 9 million (1%-2%) have some degree of RAS. The
prevalence of RAS in a population with generalized vascular disease is probably much higher.
Most prevalence studies of ARAS have evaluated clinical and racial subsets of populations with
a variable likelihood of prevalence. One, in a Medicare population, found a clinically manifest
incidence of ARAS 0.5% overall and 5.5% in the presence of chronic renal disease (22). Since
ARAS is usually asymptomatic, these results are an underestimate. In this study other clinically
significant cardiovascular diseases were frequently associated and the authors postulated that
much of the 2.6-fold higher mortality of the ARAS group was due to these (22). A study of
community-based screening found a 6.8% incidence of ARAS among the elderly (23). In
several other studies including subjects numbering from 170 to 1,700 the prevalence of
significant (>50%-70% stenosis) ARAS was high in patients with other symptomatic
cardiovascular disease, with 6% to 8% undergoing cardiac cath (24, 25, 26), and in an autopsy
group of >2,000 patients who died of stroke, 10% had >75% ARAS (27). In the American
Heart Association's Atherosclerotic Vascular Disease Writing Group on Epidemiology attempted
to summarize the available data for the prevalence of ARAS and its contribution to ESRD (28).
These authors could not find convincing data on the absolute incidence of ARAS. They
estimated that by 2010 there will be >650,000 cases of ESRD in the United States and that,
according to one report, the prevalence of ARAS in this population is 2.1% (29), though the
Writing Group warns that the actual incidence may be much higher since ARAS in ESRD
patients is not routinely looked for. Mailloux et al., in a retrospective study, found that ARAS
was the probable cause of ESRD in 16.5% of patients starting dialysis 1982 to 1985 (30). The
mortality rate of patients on dialysis for ESRD due to ARAS is significantly higher than for the
rest of the dialysis population (19).
PROGRESSION
Many of the data on progression of ARAS are probably not representative of the current state
since it was accumulated in the early to mid 1990's, which preceded current optimal medical
management, including the use of statins for lipid control, careful glucose and hypertension
control, often with angiotensin converting enzyme inhibitors (ACEIs), routine use of aspirin, and
alteration of lifestyle: diet, exercise, and weight control.
In a classic and widely quoted 1998 prospective study of progression of ARAS, 295 kidneys in
170 patients (95% hypertensive) were followed by serial duplex sonography for 33 months (3
months to 7.2 years) (31). The overall progression was 31%: 35% at 3 years and 51% at 5
years. Progression in lesions with RAS 60% was 49%. Strikingly, >33% of renal arteries
initially classified as normal and 75% of those with RAS <60% progressed to high-grade
stenosis over 5 years. Only nine arteries (3%) became occluded; of these, seven had baseline
RAS 60%. Several risk factors were found to be significantly associated with risk of
progression (hypertension, diabetes, and high-grade RAS), but the study was not adequately
powered to detect statistically significant effects of lipid levels on progression. Ninety-five
percent of subjects were treated for hypertension with an average of 2.2 drugs, yet the
baseline mean systolic and diastolic blood pressures were 163 mm Hg (range, 90-236 mm Hg)
and 82 mm Hg (range, 53-110 mm Hg). The baseline mean serum cholesterol was 216 mg/dL
(range, 125 to 395 mg/dL), 18% were diabetic, 79% had a history of smoking (25% were
current smokers), and 33% had impaired renal function. Patients continued to be managed by
their own physicians during the study and there was no attempt to coordinate optimal medical
therapy including antihypertensive drugs or risk factor modification. Other studies have found
similar rates of progression of RAS, though progression of ARAS to ESRD is rare (32, 33, 34,
35, 36, 37, 38).
TABLE 17-1 THE CLINICAL CHARACTERISTICS OF RENAL VASCULAR

HYPERTENSION
Recent-onset hypertension
Response to angiotension converting enzyme inhibitors
Onset in young women (fibromuscular dysplasia)
Onset in middle age or in the elderly (atheroma)
Difficult to control hypertension (3 drugs)
Hypokalemia (due to hyperaldosteronism)
Retinopathy and other end organ damage greater than for equivalent essential

hypertension (angiotensin II effect)
Renal dysfunction
Recurrent flash pulmonary edema (cardiac disturbance syndromes)

Continuous abdominal bruit
History of smoking or current smoker
Presence of other vascular disease
DETECTION AND EVALUATION OF PATIENTS WITH RENAL

ARTERY STENOSIS, RENAL VASCULAR HYPERTENSION,
AND ISCHEMIC NEPHROPATHY
Clinical Signs and Symptoms
RAS is often clinically silent, at least until it becomes hemodynamically significant, when it can
produce RVH or RI. Table 17-1 lists the most frequent presenting signs and symptoms of RVH,
and Table 17-2 lists those of ischemic nephropathy; each alone has a low predictive value, and
though they are rarely all present in an individual patient, cumulatively they are helpful.
TABLE 17-2 THE CLINICAL CHARACTERISTICS OF ISCHEMIC

NEPHROPATHY
No intrinsic parenchymal renal disease (usually), though in some cases it can

coexist with hemodynamically significant renal artery stenosis (RAS)
Recent-onset azotemia
Progressive azotemia
Presence of hypertension
Unequal kidney size (reflecting nonsymmetrical RAS)
Presence of other vascular disease
History of smoking or current smoker
All characteristics of renal vascular hypertension in Table 17-1 not specifically

listed
INDICATIONS AND PATIENT SELECTION FOR RENAL ARTERY

INTERVENTION
RVH, especially if due to unilateral disease, is usually easily and well controlled with modern
antihypertensive medications, especially ACEIs. Ischemic nephropathy, one of the few
reversible causes of RI in adults, is the most appropriate indication for intervention in renal
artery occlusive disease. Selection for intervention must consider and integrate the clinical,
anatomic, and physiologic status of the patient to yield the best possible risk-benefit (Table 17-
3).
Based on the clinical, anatomic, and physiologic indications and criteria above, the workup and
treatment of RAS and RVH should proceed in the framework of the algorithms below for RVH
(Fig. 17-4) and ischemic nephropathy (Fig. 17-5). RVH comprises ~1% to 5% of hypertensives
in the United States. The captopril challenge test (plasma renin activity with ACEI) is a
sensitive but nonspecific test for detection of RVH (39). Patients with a strong clinical suspicion
for RVH and a positive captopril challenge test should be further evaluated according to the
algorithm in Fig. 17-4. Often more than one of these tests is obtained, which is time-consuming
and expensive, and the results are frequently still nonconclusive. Therefore only one of these,
the one that has proven to be the most reliable in local practice, should be performed. Renal
vein renin sampling and assay (40, 41, 42, 43, 44) and renal scintigraphy (45, 46, 47) are only
reliable in patients with unilateral RAS who do not have renal parenchymal damage or RI; renal
vein rennin sampling and assay are also invasive, therefore they are rarely used. Computed
tomographic angiography (CTA) gives excellent anatomic detail but is less useful in the
presence of heavy calcification and requires nephrotoxic iodinated contrast medium, thus is not
suitable for patients with RI (47,48). MRA has been the noninvasive screening test of
preference for most clinicians since it gives anatomic as well as physiologic information about
the aorta, renal arteries, and kidneys; is considered to be nonnephrotoxic, especially in patients
with RI, and nonallergenic; and requires no ionizing radiation (47,48). Unfortunately, recent
reports of nephrogenic systemic fibrosis, a frequently fatal debilitating painful fibrosis that
affects multiple organ systems in a handful of patients (~125), most of whom have had prior RI
(49, 50, 51), may alter this practice. Although most reported cases have been due to one
formulation, Omniscan (GEHC), according to an FDA December 2006 Public Health Advisory,
all other forms of gadolinium-based contrast media may be implicated. If nephrogenic systemic
fibrosis proves to be more common than thought and no strategy to prevent or successfully
treat it is found, then other tests will have to be preferentially used. Duplex ultrasound (US) is
an excellent technique that yields anatomic as well as physiologic data, though its anatomic
resolution and ability to identify branch stenoses are less than that for CTA and magnetic
resonance angiography (MRA) (47,52,53). It is also very time-consuming, operator dependent,
and difficult to reproduce, however, it does not require ionizing radiation or nephrotoxic contrast
media, therefore it may become the technique of choice by default for identifying
hemodynamically significant RAS. If one of these
screening tests is positive or equivocal, arteriography should be performed to make the final
diagnosis.
TABLE 17-3 THE CLINICAL, ANATOMIC, AND PHYSIOLOGIC BASIS FOR

PATIENT SELECTION FOR RENAL ARTERY INTERVENTION
Clinical
1. Severe or difficult to control hypertension

2. Recent onset or progressive moderate to severe renal dysfunction
3. Recurrent flash pulmonary edema
4. Jeopardized kidney (see no. 5 under Anatomic, below)
Anatomic
1. Stenosis 70% of diameter

2. Poststenotic dilatation
3. Collateral circulation
4. Renal length at least 7-8 cm
5. Diminished renal size (jeopardized kidney)
a. Absolute renal length difference 1.5 cm
b. Documented decrease in renal length 1 cm
Physiologic evaluation of clinically and anatomically detected renal artery stenosis

techniques and their sensitivity and specificity (references)
1. Radionuclide scana (sensitivity, 64%-91%; sensitivity, 44%-98%) (45, 46, 47)

2. Renal vein renin assaya,c (sensitivity, 43%-69% without ACEI and 61-92% with
ACEI; specificity, 62%-100% without ACEI and 52%-100% with ACEI) (39, 40, 41,
42, 43, 44, 45,47)
3. Duplex ultrasoundb (sensitivity, 17%-100%; specificity, 47%-100%) (47,52, 53, 54,
55, 56)
4. Transstenotic pressure gradient 10% of peak systolic pressurec (76, 77, 78, 79,
80, 81)
Note. ACEI, angiotensin converting enzyme inhibitor.

a Unreliable in bilateral disease and renal insufficiency.
b Technically difficult and operator dependent.
c Invasive.
FIGURE 17-4. Algorithm for diagnosis and treatment of renovascular hypertension. (PRA =
pre-renal azotemia)
FIGURE 17-5. Algorithm for diagnosis and treatment of ischemic nephropathy.
Identification of patients with hemodynamically significant RAS and potentially curable ischemic
nephropathy is even simpler. Here MRA is still the first choice, but US is an attractive
alternative. Detection of significant RAS and differential renal size are key to the diagnosis.
Atheroma of the renal arteries is usually asymmetrical and therefore produces differential renal
size; medical parenchymal renal diseases usually affect the kidneys equally and produce
symmetrical reduction in size. There is little scientific evidence, but it is generally assumed that
kidneys <7 to 8 cm long will not benefit from revascularization. The resistive index is an
attractive concept for detection of kidneys with irreversible parenchymal disease (54), but it not
as reliable as initially reported and should not be used to deny treatment to a patient who
otherwise would qualify for intervention (55,56).
Because complications including cholesterol embolization can occur, it is imperative not to
intervene for anatomic RAS without adequate clinical and physiological indications, particularly
not in incidentally discovered RAS without prior clinical evaluation. Therefore, prior to renal
artery interventions the physiological significance of a stenosis should be confirmed by
demonstrating a hemodynamically significant transstenotic pressure gradient, in addition to
appropriate clinical and anatomic indications.
IS RENAL ARTERY STENOSIS AN INDEPENDENT RISK

FACTOR OR A PREDICTOR FOR MAJOR ADVERSE
CARDIOVASCULAR EVENTS?
The terms RAS and ARAS, physiologically or hemodynamically significant RAS and ARAS, and
RVH are often used interchangeably. The association of any degree (the more severe the
greater) of RAS with MACE has been frequently noted (57,58). Unfortunately, there is a great
deal of confusion and misinformation being widely quoted and misquoted regarding RAS as
being an independent risk factor for MACE. This is confusing and incorrect and sometimes used
to recommend intervention (stent) for any RAS even if the stenosis is physiologically and
clinically not significant (59), though Zeller et al. recently acknowledged that statin therapy may
be important (60). It has even been suggested by some in lectures, though not in writing, that
any, even physiologically nonsignificant, RAS can produce adverse cardiovascular effects by
mysterious hemodynamic and humoral effects. There is no evidence to support this concept. In
fact, most authors have concluded that any degree of ARAS is a predictor or marker for, and is
associated with but not an independent risk factor for, MACEs via pathways described below
and as above under Pathophysiology.
1. ARAS is highly associated with systemic atheroma in other vital vascular beds including the
coronary and cerebral, which are directly responsible for MACEs.
2. Hemodynamically significant RASthe more severe, the more so (58)produces the
following physiological effects.
i. RVH is mediated by the renin, angiotensin, aldosterone system. The hemodynamic and
humoral effects of hypertension and their action on the contralateral kidney as well as the
direct vasotoxic effects of angiotensin II are responsible for significant MACEs.
ii. Ischemic nephropathy causing RI is usually due to bilateral RAS, solitary kidney with RAS,
or, if unilateral, damage to the contralateral kidney by parenchymal disease such as
hypertensive or diabetic nephropathy. ESRD due to ARAS also has a very high association
with MACE; the median survival after starting dialysis is 25 months, and the 5-year survival
is 18% (19).
iii. Recurrent pulmonary edema and other cardiac disturbance syndromes are a relatively
frequent (>10%) presentation of hemodynamically significant bilateral RAS, solitary kidney
with RAS, or unilateral RAS and contralateral parenchymal damage (61,62). These
conditions are caused by the same anatomy and physiology as in paragraph b above and
they frequently are present in the same patient.
PROPHYLACTIC INTERVENTION OR PROPHYLACTIC

MEDICAL THERAPY FOR CLINICALLY AND
HEMODYNAMICALLY NONSIGNIFICANT RENAL ARTERY
STENOSIS?
Some advocate prophylactic intervention for asymptomatic and hemodynamically nonsignificant
RAS based on the following.
1. The difference between association or predictor and independent risk factor is
misunderstood and it is assumed that any degree of RAS is an independent risk factor for
MACE.
2. ARAS is a progressive disease (31, 32, 33, 34, 35, 36, 37, 38) and progressive worsening
of ARAS stenosis occurs despite medical therapy that effectively controls the blood
pressure (36,63).
3. Therefore, unless prophylactically and aggressively treated by mechanical (stent)
intervention, ARAS will progress to cause severe hypertension and RI, with their attendant
MACEs, at which point the disease is no longer reversible or controllable by interventional
treatment (59).
4. Early prophylactic intervention in a less diseased renal artery and aorta is technically easier
and less likely to result in complications.
These arguments are at first persuasive but are based on inadequate or incorrect assumptions
and on information that is no longer current. Most of the studies on the progression of RAS
overestimate the progression of atheromatous renal artery disease; they predate the
widespread aggressive use of statins, exquisite control of RVH by drugs specifically targeting
rennin-dependent hypertension, aggressive control of glucose, and efforts at lifestyle
modifications including smoking cessation, diet, exercise, and weight control, especially in high-
risk populations. In fact, several large studies have recently confirmed the arrest of progression
and, in some cases, regression of atheromatous plaque in the coronary and carotid arteries by
aggressive treatment with statins (64, 65, 66); there is no reason to postulate that these
effects are limited to these vascular beds and not the same in the renal circulation (60,67). It
seems reasonable, then, to treat all patients with such asymptomatic and hemodynamically
nonsignificant RAS lesions with aggressive statin therapy, aspirin, and other appropriate
medications and lifestyle modifications described previously, which have acceptable risks and
side effects when carefully monitored. This would likely produce all the potential benefits of
aggressive interventional stent treatment, whose very long-term durability
and fate are unknown, without any of its known major risks such as cholesterol embolization
and without the 15% to 20% restenosis, all of which can occur even in low-risk patients. Such
medical therapy would reduce or eliminate not only progression of ARAS, but also progression
of disease in the abdominal aorta and in other vital vascular beds. Of course, if a patient with
known ARAS is treated medically, they should be carefully monitored for development of more
difficult to control hypertension, mild RI, decrease in renal size, and progression in the severity
of stenosis. These are the same parameters that would be followed in any patient after
interventional therapy. If, despite optimal medical therapy, a patient develops RI or other signs
and symptoms described above due to progressively increasing ARAS, then interventional
treatment should be considered. There are no evidence-based clinical data to support
prophylactic renal angioplasty with stenting for clinically asymptomatic and physiologically
nonsignificant RAS; there is, however, strong evidence for prophylactic medical therapy to
arrest progression and possibly produce regression not only in the renal arteries and the aorta,
but in all areas of the vascular tree at risk by systemic atheroma even following successful
interventional therapy. Statins and risk reduction are the new paradigm for all atheroma.
RISKS, BENEFITS, AND NATURAL HISTORY

The potential risks of renal artery intervention, especially cholesterol embolization, are
underrecognized and underreported as occurring in ~3% of interventions for ARAS. These are
discussed in greater detail under Complications and Their Prevention, below. Physicians who
perform renal artery interventions must understand the nonlinear relationship of glomerular
filtration rate, which represents the amount of functional renal tissue, and serum creatinine
(SCr) and its implications for the margin of safety (Fig. 17-6).
Severe cholesterol embolization and iatrogenic renal parenchymal damage due to diagnostic
and therapeutic intravascular procedures can be masked in patients with normal
preintervention global SCr values. Half of the total renal mass (glomerular filtration rate) or one
of the kidneys can be destroyed without any change in global renal function as measured by
SCr values, although the creatinine clearance of the ipsilateral kidney will be reduced. Patients
with elevated SCr whose renal function is at the knee of this curve have very diminished renal
reserve and are at much greater risk. An additional 10% loss of renal parenchyma can put such
a patient on dialysis.
FIGURE 17-6. Renal functional reserve (glomerular filtration rate; GFR) and serum
creatinine (SCr) concentration. Note: SCr increases logarithmically only after 50% of renal
parenchyma is lost.
TECHNIQUES OF RENAL ARTERIOGRAPHY, ANGIOPLASTY,

AND STENTING
Operators should be familiar with alternative choices and their advantages and disadvantages
for puncture sitesfemoral, high brachial, radial; techniquespredilation with balloon or
dilator/sheath or no predilation, bareback, guide catheter/sheath delivery; and devices and
delivery systemslow and wide profile, that is, 0.014 to 0.035 in., over-the-wire, monorail-type
rapid exchange, and the various types of balloon expandable stents, as well as the choices of
embolic protection devices and whether or not to use them.
Intervention for ARAS must be performed with special attention to limiting nephrotoxic iodinated
contrast and unnecessary manipulation in the diseased aorta and renal artery especially in
patients with ischemic nephropathy. Intervention in FMD and other arteridites has other
technical challenges.
Choice of Angioplasty or Stent

Angioplasty should be used primarily in all nonatheromatous stenoses and in nonostial ARAS. If
angioplasty fails immediately or there is late restenosis, angioplasty can be repeated or re-
treated later by stent or other devices, but once a stent is deployed, it and its potential
complications cannot be retrieved. As described later, not all nonatheromatous stenoses
respond immediately to angioplasty, but stents should not be used indiscriminately in these
situations.
Stents should be used primarily in all ostial ARAS and in resistant or recurrent nonostial ARAS
when the patient and the renal artery are fully grown. Stents are also useful as a bailout tool for
iatrogenic atheromatous dissections; they should be used with caution in nonatheromatous
complications such as iatrogenic dissection in FMD that occurs nearer to the hilum in smaller
vessels. Many nonocclusive dissections will heal spontaneously if the patient is adequately
treated with platelet antagonists. The stenosis can then be treated 6 months later after it has
healed.
There is no role for covered stents in the renal arteries except for sealing iatrogenic ruptures.
Choice of Puncture Site

Traditionally interventional radiologists have preferred the femoral entry approach and use the
high brachial one only in cases where the femoral route is difficult or impossible, such as in
infrarenal aortic or iliac occlusions. Many cardiologists prefer the low brachial and radial
approaches. The technical and clinical success rates and complication rates of all these are
similar, though there is a learning curve for all; interventionalists should be familiar with all (68,
69, 70, 71).
Pre-, Intra-, and Postprocedural Medications

There is little or no evidence that antiplatelet drugs other than aspirin confer any short- or long-
term benefit following renal artery interventions. In patients who already have RI or in those at
increased risk such as diabetes, multiple myeloma, renal
disease, and dehydration, pre-intervention hydration with sodium bicarbonate (72) overnight
with 0.45% saline at 100 for 150 mL/hour for 4 to 12 hours prior to the procedure or, if
overnight hydration is not possible, at least 1 hour of hydration should be given, and
acetylcysteine, 600 mg twice daily on the day before and day of intervention, is also
recommended (73,74). The total volume and concentration of iodinated contrast should be
minimized.
During the procedure, patients should receive approximately 5000 IU of systemic heparin and
200-m aliquots of intrarenal artery nitroglycerine to prevent or diminish spasm (68, 69, 70).
ATHEROMA
In the last decade equipment has become lower-profile and more flexible, thus mechanical
failures and complications have become or should be negligible. There is also a growing
awareness that the risks of microcholesterol embolization and iodinated contrast nephrotoxicity
are the two major risks of renal artery interventions, especially in the elderly atheromatous
patient with RI. Current techniques concentrate on reducing or eliminating these major risks by
1. limiting the amount of nephrotoxic iodinated contrast medium,
2. limiting and simplifying the manipulations in the diseased abdominal aorta and renal arteries,
and
3. using protection devices to prevent cholesterol embolization during stent placement.
FIGURE 17-7. The influence of flush catheter shapes on diagnostic information and
contrast use. Aortograms in the same patient before (A) and after (B) right renal
angioplasty for FMD. Ten millimeters of half-strength contrast was used for each
aortogram, delivered at 10 mL/second and filmed at 4 frames/second. (A) and (B) were
obtained at the same time after the beginning of contrast injection and the sideholes of the
catheters were positioned at the same level. A: Aortogram using the pigtail catheter. B:
Aortogram using the OmniFlush catheter results in less cephalad reflux (horizontal arrows),
denser opacification of the renal arteries and the aorta (arrowheads), less reflux into the
superior mesenteric artery branches (curved arrow), and more uniform mixing of contrast
in the iliac arteries (notched arrowheads) than in A, using the pigtail. (See the color insert.)
These are discussed in more detail under Complications and Their Prevention.
Aortography
Aortography demonstrates the presence, location, and extent of atheromatous disease in the
aorta and the renal artery and allows for planning the renal artery intervention. Flush catheters
that minimize iodinated contrast should be used for aortography. The OmniFlush
(AngioDynamics, Queensbury, NY) prevents cephalad reflux into the celiac and superior
mesenteric arteries, which can overlap the renal arteries and also steal contrast from the
desired areas of interest, and also delivers a more concentrated bolus to the area of interest.
Since the renal arteries originate at the L1 vertebral body, the sideholes of the catheter are
positioned at the T12-L1 interspace (Fig. 17-7).
A prior MRA or CTA is very helpful in determining the optimal obliquity for performing diagnostic
aortography for renal artery disease. Aortography, selective renal artery catheterization,
angioplasty, and stent deployment in the right renal artery are generally performed in the 20- to
30-degree LAO projection because the right renal artery usually arises ~30 degrees ventrally to
the equator of the aorta and in the AP projection for the left renal artery, which originates
slightly dorsal to the equator (Figs. 17-8, 17-9 and 17-10) (75).
Arteriography should begin with an aortogram, never with selective catheterization, in a
potentially very diseased aorta, even if a prior CTA or MRA is available (Fig. 17-11). If a
proximal/ostial RAS is identified by aortography, selective catheterization is contraindicated
unless an intervention is planned,
especially if RI is present. An ostial or proximal RAS is always better defined by aortography
than by selective arteriography because the selective catheter tip will either be distal to the
stenosis or just proximal to it, in which case it could dissect or otherwise injure the vessel or
cause cholesterol emboli during the injections or manipulations; indeed diagnostic selective
arteriography using nephrotoxic iodinated contrast is contraindicated in atheromatous disease
it incurs all the risks of an intervention without any of the potential benefits.
FIGURE 17-8. The right renal artery origin is 30 degress ventral, and the left 7 degrees
dorsal, to the midcoronal plain of the aorta (0 degrees). (After Kim PA, Khilnani NM, Trost
DW, et al. Fluoroscopic landmarks for optimal visualization of the proximal renal arteries. J
Vasc Interv Radiol. 1999;10(1):37-39, with permission.)
Selective Catheterization and Arteriography

In patients with ostial ARAS no information can be obtained from a selective arteriogram that
should influence decision making; the improved demonstration of peripheral pruning of branches
and a thinned cortex in nephrosclerosis is not quantitative, will also be apparent on the
aortogram (Fig. 17-12), and, in any case, should not influence the decision whether or not to
undertake intervention. Treatable, solitary, focal proximal branch disease is extremely rare in
ARAS, and although it can produce RVH, it does not produce RI. Multiple small-branch RAS is
present only in severe diabetics or ESRD; these diffuse distal lesions are not suitable for
interventional treatment and severe diffuse parenchymal disease is always present. However,
despite the small likelihood of improving renal function, in the rare patient with renal failure with
a kidney >7 to 8 cm long, if a hemodynamically significant main RAS is present, it should still be
treated even if multiple small-branch stenoses are identified. In these predialysis or dialysis
patients
renal function cannot be made worse, and most of the other risks of catheterization will already
have been taken.
FIGURE 17-9. The importance of using the correct projection for stent deployment and
imaging. The stent was correctly deployed in the 30-degree LAO projection and extends
only a few millimeters into the aortic lumen (solid LAO line). If the stent had been deployed
in the AP projection (solid AP line), it would not have extended into the aortic lumen
(vertical dotted line with curved arrow) and an AP aortogram would have misleadingly
shown it to have been properly placed.
FIGURE 17-10. The importance of deploying and imaging stents in the correct obliquity. A:
A 30-degree LAO aortogram shows the right renal artery stent (arrowheads) to have been
correctly placed and extending a few millimeters into the aorta. B: A 40 RAO aortogram
appears to show more than half of the stent extending into the aorta. Had the stent been
placed in this projection, it would not have covered the ostium and would not have
extended into the aorta.
FIGURE 17-11. The usefulness of preintervention MRA for identifying the optimal obliquity
for aortography. A: Axial MIP demonstrates ostial stenosis (arrow) of the right renal artery
that arises 30 degrees ventrally and a moderate diffuse nonostial left RAS (arrowhead). B:
Reformatted 30-degree LAO projection MRA demonstrates both lesions. C: A single
aortogram in the 30-degree LAO projection using only 10 mL of half-strength iodinated
contrast (5 mL of full-strength contrast) demonstrated both lesions well and the partially
subtracted view of C guided selective catheterization for stenting using the relationship of
the bony structures to the stenoses as a guide.
When bilateral ARAS is present, the technically easier side, usually the one with the larger
kidney, should be selectively catheterized and evaluated first by obtaining selective pressure
measurement after the aortogram. If a significant gradient is present, the ARAS is treated. If
there is no gradient, the contralateral side should be evaluated and treated if appropriate. This
strategic sequence is important: if the technically more difficult stenosis is attempted first and
does not succeed or results in a complication, then treatment of the easier contralateral side,
which could potentially benefit the patient more, may not be attempted; or if it is tried when
both the patient and operator are exhausted, that, too, is more likely to fail or result in a
complication. It is important to remember that RVH due to unilateral RAS is much easier to
treat medically than bilateral RAS and that RI can be improved by treating only onethe more
viablekidney; the enemy of good is perfect. Obviously the contrast sparing strategies
described in this chapter are especially important in these patients. Recanalization of occlusions
should only be attempted in patients with RI when the contralateral kidney does not have
adequate function despite having a patent artery.
FIGURE 17-12. Nephrosclerosis. Aortogram in a patient with SCr of 6 mg/dL. There was
no gradient across the mildly stenotic stent. The distal renal arteries are pruned and there
is no cortical filling. There is delayed transit and emptying of contrast from the affected
kidney and renal arteries due to increased peripheral resistance in the nephrosclerotic
kidney (arrow). (The arteriographic appearance following diffuse cholesterol embolization is
very similar). In normal kidneys contrast clears from the renal arteries by the time it clears
from the aorta (arrowhead). In this case, even if there were a severe RAS, there would not
have been a pressure gradient.
Pressure Gradient Assessment

Visual estimation of the degree of stenosis, even when severe, is unreliable (76, 77, 78, 79,
80). If an intervention is planned, selective catheterization and pressure measurements should
be obtained prior to intervention, no matter how severe the stenosis appears to be visually.
In the past most definitions of minimum threshold hemodynamically significant gradients were
arbitrary: a 10 or 20 mm Hg absolute peak systolic gradient or, as we advocated, a 10% peak
systolic gradient that takes into account the effect of different absolute blood pressures. A
recent very elegant study by De Bruyne et al. (81) demonstrated that we had guessed
correctly: graded reduction of renal artery pressure by balloon inflation to produce unilateral
RAS immediately following stenting of the same artery and serial renal vein renin sampling
showed that hypersecretion of renin from the ipsilateral kidney began at a threshold of a 10%
peak systolic gradient.
Ideally, gradients should be measured with the lowest-possible-profile instrument, which adds
the least to the severity of a stenosis. A 0.014-in. pressure wire is ideal, but it is expensive; a
4-Fr catheter clearly contributes more to an existing stenosis, but it is very useful in excluding
from unnecessary intervention those patients who do not meet even this lower threshold of a
10% gradient. In any case, clinically and hemodynamically significant ARAS rarely presents with
low or borderline gradients. To measure the aortorenal gradient a catheter/pressure wire must
be placed across the RAS and a simultaneous aortic pressure obtained with a multichannel
monitor. If a multichannel monitor is not available, serial alternating pressures should be
compared. The aortic pressure can be obtained with a sheath at least 1 Fr larger in diameter
than the catheter through it in either the aorta or the femoral artery if there is no significant
aorto-iliac disease as demonstrated by prior comparison of aortic and femoral pressures.
If there is no gradient, intervention should not be performed; this signifies either a
nonhemodynamically significant RAS or severe nephrosclerosis, with peripheral vascular
resistance so high that pressures are equalized even across a hemodynamically significant RAS
(Fig. 17-12).
A recent modification of the pressure gradient measurement is calculation of the renal fractional
flow reserve (FFR) after administration of papaverine, a vasodilator (79). The authors claim
that in visually moderately severe RAS, the FFR is a better predictor of blood pressure
response to stenting than the resting pressure gradient. Unfortunately, FFR has not been
validated in RI, a better end point for evaluation of a successful procedure.
It is recognized that not all patients with RAS with a significant gradient will respond clinically to
intervention. This is usually due to the fact that RVH coexists with essential hypertension, but
there may be extensive parenchymal and microvascular damage; in patients with RI there may
be too much parenchymal damage for a kidney to benefit from increased perfusion, and
complications such as cholesterol emboli or contrast nephrotoxicity may occur.
Contrast Media
Since many patients with ARAS have marginal or poor renal function, the total amount of
iodinated contrast medium should be limited. Despite all the hype to the contrary, the
nephrotoxicity of all forms of low-osmolar contrast media is similar and is primarily related to
the total volume and concentration used (82,83), though there are some data supporting the
possible benefit of iodixanol (84). To accomplish a reduction of total iodinated contrast,
interventionalists should become familiar with, and their equipment optimized for, a half-
strength 30% concentration (150 mg I/mL) contrast medium. Aortography can be performed
using a total volume of only 10 mL, injected at 10 mL/second. If the renal artery origin(s) is
(are) not satisfactorily demonstrated (prophiled) with the first half-strength contrast aortogram,
further targeted repeat aortograms in other obliquities can be performed, with the catheter
repositioned at the now precisely known level of the renal arteries. This is rarely necessary, but
should it be, only 5 to 10 mL of full-strength contrast is adequate. This technique results in
images that are diagnostic and allow for successful identification and confirmation of the
disease preintervention, which has frequently already been demonstrated noninvasively.
Although the quality of the images is not as pretty as those obtained with full-strength
iodinated contrast, it is equal or superior to those with intra-arterial CO2 (85) or gadolinium and
much less cumbersome to perform than the former.
FIGURE 17-13. The no touch technique for renal artery catheterization. The guide sheath
or guide catheter (curved arrow) is kept from contact with the aortic wall by a 0.035-in. J-
tipped guide wire (vertical arrow) while a 0.014-in. guide wire (arrowhead) is advanced
through the RAS for stenting. Once the wire successfully traverses the stenosis, the larger
wire is removed.
Selective Renal Artery Catheterization and Arteriography

Catheters for selective catheterization and directing the guide wire across the stenotic renal
artery include visceral shapes such as the Cobra, Simmons, Shepherd's crook, Sos Omni
Selective, and shaped guide catheters or even thinner sheaths for initially passing the guide
wire, but these are all potentially very traumatic in the often very diseased abdominal aorta.
Most interventionists move and rotate these catheters back and forth in the abdominal aorta
with multiple test injections to locate the stenotic renal artery. Inadvertent shifting of plaque may
result from such manipulations and produce occlusion of the renal artery and cholesterol
embolization; the test injections can quickly add up to > 50 mL of contrast.
The amount of manipulation in the often diseased abdominal aorta must be minimized and the
techniques used must be as atraumatic as possible. These principles were advocated in a
recent paper (86), though it did not offer any new techniques for accomplishing this goal. The
no touch technique (Fig. 17-13), recently described by Feldman et al., for minimizing contact
between the guide catheter and the aortic wall and the renal ostium is more constructive (87).
The Sos Flick technique (Figs. 17-14 and 17-15), pioneered by us, also diminishes
manipulations and contact with the diseased vessel wall and eliminates contrast test injections.
It begins by first identifying the location of the renal artery and the stenosis in relation to the
bony landmarks (spine and ribs) and calcifications in the aorta and the renal artery by using a
nonsubtracted or partially subtracted aortogram image displayed on a television monitor or as
hardcopy on a view box. The SoftVue (soft-tipped) Sos Omni Selective (AngioDynamics,
Queensbury, NY) catheter was designed for selective catheterization of the renal artery and for
crossing stenoses. This recurve design is similar to the Simmons shape but has a shorter side
arm and tip length, and its shape is significantly easier and less dangerous to reconstitute
below the aortic arch. The catheter is pulled below the renal artery in the aorta, with only the
smooth, soft, and long arc of the Bentson-type guide wire touching the aortic wall, while the
soft floppy tip of the wire points into the lumen. Selective catheterization of the stenotic renal
artery is performed with the image intensifier in the oblique projection where the origin
(nubbin) of the renal artery is in profile on the initial aortogram. Below the renal artery the
Bentson-type guide wire is withdrawn until ~1 cm extends from the catheter tip. The catheter is
then slowly advanced cephalad, with the catheter tip pointed laterally toward the origin of the
renal artery. This maneuver deflects the tip of the wire parallel to the aortic wall, and even
slightly pointing toward the lumen. When the catheter/wire combination reaches the nubbin of
the stenosis the wire will readily enter it with a characteristic lateral flick and then it can be
gently advanced across the lesion. If the stenosis is not successfully entered, the guide wire is
carefully re-extended as the catheter is advanced cephalad, then the catheter is returned to
below the renal artery as before. The flick maneuver is again attempted but with the catheter
tip in a slightly different dorsal or ventral orientation. It is unusual not to enter the artery in three
attempts, and with experience, entry usually occurs on the first attempt. This maneuver
eliminates the use of contrast for selective catheterization.
FIGURE 17-14. The Sos Flick technique of selective renal artery catheterization for ostial
RAS using the Sos Omni Selective recurve-type catheter. A: The catheter and soft
Bentson guide wire have been pulled below the stenosis. B: The wire is pulled back into
the catheter, leaving ~1 cm out. C: The catheter and wire are advanced cephalad. D: The
wire flicks laterally when it reaches the nubbin of the stenotic or occluded renal artery. E:
The wire is gently advanced across the stenosis.
FIGURE 17-15. Technique of crossing a stenosis and performing angioplasty. These
images are similar to the diagrams in Fig. 17-14. A: Subtracted aortogram shows severe
proximal right renal artery stenosis (arrowhead). B: Nonsubtracted aortogram serves as a
pseudo-road map on an adjacent monitor, allowing the relationship of the vessel, the
stenosis (arrowhead), and the underlying bony structures to guide catheterization. Note:
The position of the patient and the imaging chain must be identical to that in which the
aortogram was obtained; otherwise parallax will displace the apparent and real positions of
these structures. C: The catheter is withdrawn to below the stenosis with a smooth arc of
the Bentson wire preventing aortic wall injury. D: The wire is withdrawn until only ~1 cm
extends out from the catheter. The wire catheter combination is advanced cephalad in the
plane in which the ostium is best profiled and the wire forms a gentle, nontraumatic arc
with the aortic wall. E: When the wire (arrow) reaches the vessel nubbin (arrowhead), it
flicks laterally into it. F: The wire is then gently advanced through the stenosis. G: The
soft-tipped version of the Sos Omni Selective catheter used in the flick technique. H: The
catheter is pulled down over the wire across the stenosis. I: The Bentson wire is removed
and exchanged for a stiffershaft, soft tapered-tipped TAD II wire, which is advanced
further into the artery until its stiff shaft is well across the stenosis. As the wire is advanced
beyond the stenosis its tip may spontaneously form a small J configuration. J: Angioplasty
or stenting can now be performed over the firm wire without risk of losing access. (See the
color insert.)
Following successfully crossing the lesion, the transstenotic pressure gradient must be
documented; this is also the time to administer systemic heparin and intra-arterial antispasmotic
medications discussed in more detail under Complications and Their Avoidance, below. In the
presence of a significant gradient, the soft guide wire is exchanged for a stiffer 0.035-in. wire
such as the TAD II (Mallinckrodt, St. Louis, MO), whose shaft can be precurved to fit the
course from the aorta into the renal artery, or, if a low-profile system is used, for an 0.018-to
0.014-in. wire. Beyond the stenosishe, TAD II guide wire will often form a soft small J at its tip
as it meets the vessel wall. This is a very safe way to advance it (Fig. 17-15). If it needs to be
advanced further, into a small branch, it can be gently withdrawn until the tip straightens, then
readvanced. Alternatively a protection filter or occlusion device may be deployed and will act
as the guide wire for intervention. J-tipped guide wires are stiff and initially tend to curve into
the vessel wall when advanced out of the catheter unless meticulous tip exchange technique is
used. They also are too large in diametereven the 2-mm-radius Rosen wireto advance into
branches without causing severe spasm and or dissection, therefore they should be used with
great caution in all renal artery interventions. The initial catheter is then exchanged for
a guide sheath or catheter for introduction of an angioplasty balloon or stent delivery catheter.
The guide sheath or catheter can be introduced at any point starting prior to aortography to just
after the stenosis has been crossed and a gradient has been demonstrated. A guide sheath
should never be advanced into an artery or through a stenosis without first fully inserting its
tapered inner dilator. It is preferable to enlarge the puncture site beyond 4 Fr only after the
need for intervention has been confirmed.
FIGURE 17-16. Evaluation and treatment of short atheromatous right renal artery
occlusion. Both kidneys were smaller than 10 cm and the patient had RI. A: AP aortogram
demonstrates short occlusion of the right renal artery and reconstitution of the distal renal
artery (notched arrowhead), with an irregular saccular area of the aorta (arrow) that was
misinterpreted at another institution as the nubbin of the occlusion. Several unsuccessful
attempts were made to recanalize the occlusion from within this. There is also a severe
ostial left RAS (curved arrow), which was stented prior to recanalization of the right renal
artery. B: A 25 LAO aortogram demonstrates that the saccular dilatation is an ulcerated
plaque and the real nubbin is now well seen (arrowhead). C: Successful stenting of both
renal arteries. D: Stiff AngiOptic version of the Sos Omni Selective used for recanalization.
E: Successful crossing of the occlusion with a hydrophylic guide wire (arrowhead). F: After
the catheter is pulled across the stenosis its intraluminal position is confirmed and the
hydrophylic guide wire is exchanged for a nonhydrophylic TAD II wire (notched arrowhead)
over which the procedure is completed after confirmation of intraluminal crossing of
stenosis. (See the color insert.)
Most occluded renal arteries also have a few-millimeterlong, funnel-shaped origin (nubbin)
proximal to the occlusion, which can be identified and entered as described above for stenoses;
if no nubbin is identified, percutaneous recanalization cannot and should not be attempted (Fig.
17-16) (88). Almost all atheromatous renal artery occlusions in viable kidneys are very short
and extend <1 cm beyond the ostium, therefore using large volumes of contrast to visualize the
reconstituted distal vessel is not justified. Obviously noninvasive imaging prior to intervention is
helpful to confirm this assumption. However, if there is a viable and >7 to 8-cm kidney, there is
a vessel leading to it beyond the occlusion, and this vessel will be injected after recanalization
to make sure that the catheter is intraluminal. For crossing occlusions initially a straight
hydrophylic guide wire is used, which is forced (pulled) against the funnel-shaped nubbin of the
origin of the occluded renal artery by the stiffer AngiOptic version of the Sos Omni Selective
(Angio-Dynamics) catheter. As soon as a catheter is successfully advanced across the
occlusion its intraluminal position must be documented by hand injection of a small amount of
contrast; if the wire is extraluminal, the procedure is terminated and the perforation embolized if
necessary. If the distal lumen is successfully entered, the hydrophylic wire should be exchanged
for a nonhydrophylic, stiffer wire such as the 0.035-in. TAD II (Mallinckrodt, St. Louis, MO) or
an appropriate 0.014- to 0.018-in. wire as soon as practical, since hydrophylic wires are more
likely to produce vessel perforation or be withdrawn from the vessel inadvertently. After this,
stenting proceeds as described for stenoses above.
Renal Artery Angioplasty and Stenting

Ostial and most proximal ARAS lesions rapidly recoil following angioplasty and require stent
placement for lasting benefit. The balloon is perpendicular to the aortic wall and the forces
exerted by the balloon are parallel to the long axis of the aortic wall; this is analogous to trying
to dilate a hole in the side of a somewhat elastic can. In contrast, when dilating inside an artery,
the forces of the balloon are perpendicular to the stenosis and parallel to the wall, analogous to
dilating a thin-walled narrowed tube; focal nonostial ARAS >1 cm from the ostium in the renal
artery usually responds well to angioplasty alone, as do the rare significant, treatable,
atheromatous focal branch stenoses. For bifurcation stenoses the kissing wire/balloon
technique should be used (Fig. 17-17).
Stenting
Currently available self-expanding stent designs are not ideal for RAS, therefore only balloon
expandable stents should be used in the renal artery. There are several techniques for stent
deployment. These include predilation with a relatively small, 5-mm-diameter, balloon or
tapered dilators within a sheath that is advanced across the stenosis. The bareback technique
utilizes a guide sheath or catheter that never crosses the lesion and uses lower-profile 0.018-in.
or smaller systems. These lower-profile systems are preferable for treatment of accessory
renal arteries 4 cm in diameter. All 0.035-in. and many 0.014-in. compatible balloon catheters
and stents are available with an over-the-wire configuration; 0.018-in. and smaller devices are
available with monorail-type rapid-exchange designs. Monorail-type rapid-exchange balloon
catheters are easier and quicker to insert and exchange for coronary use, but this advantage is
less for the shorter catheter/wire length required for renal artery interventions (Fig. 17-18). The
major disadvantage of the monorail system is its lack of a wire lumen through the entire length
of the catheter, which makes it impossible to inject contrast and obtain pressure
measurements, and the wire cannot be exchanged during intervention.
FIGURE 17-17. Atheromatous bifurcation stenosis. Use of the kissing wire alternative to
the kissing balloon technique. (Note severe atheroma of the abdominal aorta.) A: There is
an irregular severe stenosis of the main renal artery extending into the origin of the ventral
and dorsal branches (arrowhead). B: Through a guide sheath wires are inserted into both
branches. C: Selective arteriogram confirms the correct placement of the wires and the
location of the stenoses (arrowhead). D: The stenoses are dilated one at a time, while
access to the other branch is preserved. Simultaneous kissing balloons would have been a
good alternative, especially if dilating one branch had compromised the other. E: The
stenoses are successfully dilated.
Many interventionalists still favor the technique using a 0.035-in. system and predilating with a
35- to 65-cm-long, 6-Fr sheath with a tapered tip introducer. For balloon/stent sizing from the
aortogram the length of the curved tip of the OmniFlush (AngioDynamics) catheter can be used;
the distance from the top of the curve to the bottom of the tip is always 15 mm, and this portion
of the catheter is always next to and in the same plane as the renal arteries, so the
magnification of each is the same; marker sizing catheters are no more accurate. Electronic
measurement using the diameter of catheter shafts is inaccurate. The stent premounted on a
balloon catheter is delivered through an appropriately sized guide sheath (for 0.035-in. wire-
based systems) into the stenotic area. The guide sheath is then withdrawn into the aorta,
leaving the balloon/stent combination over the guide wire in place. An angiogram is performed
through the sheath in the appropriate oblique view (the x-ray beam should be perpendicular to
the long axis of the origin of the renal artery from the aorta) to
aid in the accurate placement of the stent in the renal artery. Contrast injections for stent
positioning are performed using only 5 mL of 30% (half-strength) iodinated contrast injected at
7 mL/second. Minor adjustments in the position of the stent can generally be easily performed
by advancing or withdrawing the balloon catheter with the mounted stent prior to deployment.
The guide sheath/catheter itself can be used to help in stabilizing the position of the stent during
these maneuvers, but this should only be used as a last resort since the stent can be damaged
by the guide sheath/catheter.
FIGURE 17-18. Ostial right main and ostial accessory renal artery stenoses using high-
and low-profile systems. A: After the 6-mm right main renal artery was stented, the 4-
mm accessory branch (arrowhead) was also treated. B: The stenosis was initially crossed
with a 4-Fr Sos Omni Selective catheter and a Bentson-type guide wire. The wire was
exchanged for a 0.014-in. wire and a monorail-type, low-profile, rapid-exchange stent
system was positioned (arrowhead) for stenting using the 6-Fr sheath already in the aorta.
C: The stent was successfully deployed (arrowhead). D: Completion arteriogram following
successful stenting of the accessory artery (arrowhead).
The stent should be deployed with a couple of millimeters extending into the aorta and a few
millimeters extending past the stenotic lesion. Stent deployment is inherently imprecise. Some
stents shorten slightly when expanded. The pulsation of the aorta and the renal artery during
the cardiac cycle produces a moderate amount of unpredictable movement of the balloon
catheter/stent combination. There may also be some difficult-to-control movement (watermelon
seeding) of the balloon catheter/stent during balloon inflation.
For these reasons, we prefer to deploy 15-mm-long stents for most ostial stenoses. If too
short a stent is used or if it is inaccurately placed, then a second stent partially overlapping the
first one must be deployed to cover the entire lesion and extend into the aorta (Fig. 17-19). This
may decrease long-term patency due to extra foreign material and increases the risk of
complications. After stent deployment to remove some of the stiffer and bulkier balloon designs
from the stent, the sheath should first be gently advanced into the stent as far as it will easily
go over the trailing end of the balloon, with the balloon deflated and its lumen open to air. This
maneuver wraps the balloon to minimize the risk of the balloon wings catching in, and
inadvertently dislodging, the deployed stent during balloon withdrawal.
Following the intervention, a completion angiography must be performed to assess the result,
usually through the guide sheath/catheter, and retaining the guide wire across the treated lesion
in case further intervention is necessary (Figs. 17-20, 17-21 and 17-22) (70,89).
Restenosis usually develops intrastent but may occur at either end. Proximal restenoses are
usually due to incomplete covering of the ostium and should be treated by extending the stent
by placing a second one within it (Fig. 17-19). Instent restenoses are usually treated first by
cutting balloon angioplasty and, if there is an inadequate response or for rerestenoses, by
deploying a second stent within the stent. Distal restenoses should be treated by angioplasty
and, if that is unsuccessful, by cutting balloon angioplasty or by extension of the stent. These
recommendations are based on anecdotal experience, not scientific data.
FIGURE 17-19. Malpositioned stent that did not completely cover the renal artery ostium
and resulted in restenosis. A: There is severe focal ostial restenosis (arrow). B: There is a
short gap in the coverage of the ostium (arrow). The operator either deployed the stent
using the wrong projection or tried to be too precise in deployment at the aortic wall and
left 1 mm of the ostial stenosis uncovered. C: Successful placement of the second stent
within the first, completely covering the ostium (arrow).
FIBROMUSCULAR DYSPLASIA, ARTERIDITES, AND BRANCH

STENOSES
The techniques for treating FMD and other nonatheromatous lesions are adaptations of those
previously described for atheromatous lesions. There are differences, however. If the aorta and
renal arteries are free of atheroma, cholesterol embolization and RI are not a problem, but
spasm is far more likely (90). The most frequent form of FMD, medial fibroplasias, responds to
angioplasty at low pressure and restenosis is rare; intimal fibroplasia, neurofibromatosis, and
Takayasu arteritis are usually resistant to angioplasty and require prolonged high-pressure
inflation (91).
FIGURE 17-20. The importance of retaining access prior to the completion arteriogram. A:
Nonostial proximal atheromatous renal artery stenosis (arrowhead). B: Iatrogenic
dissection following angioplasty (arrowhead); note that the wire is retained across the
stenosis. C: Successful treatment of dissection by deployment of stent (arrowhead)
without having to recross the dissected stenosis.
Generally, there is no place for stents in the percutaneous treatment of FMD; even
nonocclusive dissections will usually
heal spontaneously if treated with platelet inhibition, and once they are healed, if still
symptomatic, repeat angioplasty can be attempted. The renal artery is smaller in diameter in
the mid to distal renal artery and near the hilum, thus stents must be of a smaller diameter and
may interfere with bypass surgery.
FIGURE 17-21. Nonostial ARAS successfully treated by balloon angioplasty. A: Severe
irregular focal stenosis (arrowhead). B: Successful angioplasty (arrowhead). C:
Intravenous digital subtraction angiography followup 5 years later shows mild, clinically
nonsignificant restenosis (arrowhead). The patient, a fireman, remained normotensive and
on active fire duty without antihypertensive medication.
Aortography
An AP aortogram is usually adequate to identify the areas of stenosis and the location of the
main renal arteries to guide selective catheterization.
Selective Catheterization and Arteriogram

To fully identify the extent and severity of main and branch RAS in FMD, multiple oblique views
each orthogonal to different portions of the main renal artery are necessary, especially in
diffuse FMD (Figs. 17-23 and 17-24). Having the patients take a deep breath helps to
straighten out the renal artery and better visualize these stenoses. It is difficult to visually
estimate the severity of multiple beaded membranelike stenoses of medial FMD, and even
measuring gradients after crossing the stenosis may be misleading because the catheter and
the guide wire push the offending valvelike membranes away from the lumen toward the wall of
the artery. Therefore one must rely on the presence of hypertension and secondary signs such
as collaterals (rarely present) and smaller ipsilateral kidney and on physiologic tests such as
scintigraphy and selective renal vein renin assay to confirm the physiological significance of the
RAS. Initial selective arteriography can be accomplished via a multitude of selective catheters.
Once intervention has been decided on, the stenosis must be crossed and a guide
sheath/catheter deployed in the proximal renal artery for control contrast injection and delivery
of drugs. Alternatively the renal artery can first be engaged by a guide catheter and the
selective arteriograms and guide-wire introduction performed through it. Hydrophylic wires
should not be used since they are prone to produce dissection in FMD. The stenosis should be
initially crossed by a floppy-tipped but stiff-shaft guide wire such as the TAD II if a 0.035-in.
system is used or its equivalent 0.014- to 0.018-in. version if a lower-profile system is desired.
If a recurve-type catheter such as a shepherd's crook or Sos Omni Selective is used, it must
have a stiff enough primary curve to resist being backed or buckled out of the renal artery when
the stiff part of the guide wire is advanced into it, especially in very caudally oriented renal
arteries. The Angioptic version of the Sos Omni Selective catheter is suitably stiff. After intra-
arterial nitroglycerine is given, the wire is very gently and slowly advanced out of the catheter
tip to avoid dissection (Fig. 17-24F and H-I). Often, as it first contacts the vessel wall or as it
meets the first irregularity in the vessel wall, the soft straight platinum tip of the wire will form a
small J, which will safely push through the stenoses by gently pushing the webs out of the way.
If such a J is not formed, the wire should be carefully advanced until the stenosis is crossed. If
there is difficulty in advancing the wire, it should not be forced lest it dissect the artery.
Maneuvers such as having the patient cough or take a deep breath and exhale change the
relationship of the wire tip to the stenosis and may facilitate safely crossing it. Once the tip of
the wire is through the stenosis it will often straighten out as it enters a branch. These floppy-
tipped straight wires are safer than preshaped J-tipped wires, whose tip diameter is too large
to safely lodge in distal branches. The stiff wire will change the orientation of and straighten the
artery and therefore the location of the lesions will no longer correspond to that seen on the
selective arteriogram (Fig. 17-24D). It is therefore important to obtain a selective arteriogram
over the guide wire through the lesion, especially if the stenosis extends near to or into a
branch, and the appropriate placement to the often overlapping balloon positions for
angioplasty will be based on the relationship of the vessel to the adjacent bony structures.
Roadmapping is not useful due to respiratory motion. Overlapping inflations of an appropriately
sized balloon should be performed starting distally and proceeding centrally. Generally medial
FMD will respond to low-pressure inflations, but these should be prolonged for at least 1 minute
to allow for the lesions to be completely dilated. It is important to achieve a cosmetically good
result that eliminates the stenoses completely and results in a smooth vessel wall; incomplete
results not only will result in a lesser immediate blood pressure benefit but will predispose to
recurrence. If the initial result is inadequate, redilating with a 1 mm greater in diameter should
be considered.
Stenoses due to intimal fibroplasia (short tubular stenosis), neurofibromatosis, and Takayasu
arteritis are resistant to balloon inflation and may demonstrate little or no improvement following
angioplasty. Interestingly, in many such cases over the course of several weeks to months, the
blood pressure improves and the arteriographic appearance of the lesions becomes normal
(Fig. 17-25A to D) (91).
The temptation to deploy stents must be resisted (92) for several additional reasons: the
arteries may be small; the arteries will/should grow and the stent will not; the stent will
inevitably be close to the renal artery bifurcation and will prevent bypass surgery; and, of
course, the durability and patency of stents over the lifespan of a child are not known. Cutting
balloons in such cases may be helpful, but they should be used with great caution since only
anecdotal cases have been reported.
FIGURE 17-22. Severe ostial ARAS in solitary kidney in a patient with RI and uncontrolled
hypertension. A: There is moderately severe ostial ARAS (double arrowheads). Note the
diffuse calcification of the aortic wall, with plaque between the calcium- and the contrast-
filled lumen (arrows). These images illustrate how aortic plaque engulfs the renal artery
ostium and forms ostial RAS. B: Angioplasty produces only minimal improvement (double
arrowheads). C: Stenting is successful (double arrowheads). D: One and one-half years
later the stent shows only minimal neointimal hyperplasia (double arrowheads). Before
stenting the nuclear study is normal pre-ACEI (E) but demonstrates virtually no function
post-ACEI (F). Following successful stenting both pre-ACEI (G) and post-ACEI (H) scans
are normal.
FIGURE 17-23. A 35-year-old hypertensive woman with medial fibroplasia involving the mid
to distal third of the right renal artery. A: Pre-angioplasty demonstrates the typical string-
of-beads appearance (arrowhead). B: Postangioplasty all traces of irregularity are
eliminated by gentle, slight overdilation (arrowhead). C: Seven years later the artery is still
normal and the patient is normotensive. (The follow-up study is courtesy of Dr. Fred Keller,
Dotter Interventional Institute, Oregon Health Sciences University, Portland.)
FIGURE 17-24. An 80-year-old woman with severe hypertension resistant to four drugs
and a combination of FMD and bilateral ostial ARAS. A: Aortogram obtained with 10 mL of
a half-dilution of contrast injected at 10 mL/second demonstrates bilateral ostial atheroma
(arrowheads) and extensive right-sided FMD (arrow). B: Following successful left renal
artery stenting, a selective right renal arteriogram in 35-degree RAO allows for better
visualization of the mid third of the renal artery (lower eclipse with arrowhead). C:
Selective arteriogram in 25-degree LAO allows for better visualization of the proximal third
of the renal artery including the ostium (upper eclipse). D: Selective arteriogram in 35-
degree RAO injected through a 5-Fr guide sheath in the proximal renal artery over a TAD II
guide wire. Note that the renal artery is straightened out and all lesions but the ostial
stenosis are well demonstrated and can be treated by angioplasty knowing their exact
location. E: Completion arteriogram in 25-degree LAO demonstrates successful
angioplasty of the FMD. The ostial stent was successfully deployed in this projection. F:
Early deployment of the TAD II guide wire. Note that the flexible 0.018-in. straight tip of the
wire is gently advanced a few millimeters into the artery. G: After a few millimeters, the tip
meets a vessel wall irregularity and forms a soft flexible J. H: The J tip is gently advanced
through the webs of FMD. I: The J tip is safely located in a branch; the angioplasty and
stenting can now be performed through the guide sheath over the TAD II wire (as shown in
D and E).
FIGURE 17-25. A 14-year-old hypertensive boy with Takayasu arteritis. There is a delayed
response to angioplasty. A: Aortogram demonstrates a solitary left kidney with a severe
stenosis of the distal main renal artery (arrowhead) and a milder stenosis extending into
the origin of the ventral branch (inferiorly). There is also ostial stenosis and proximal
occlusion of the superior mesenteric artery (arrow) and large collaterals from the inferior
mesenteric artery (notched arrowhead). B: Selective left renal arteriogram better
demonstrates the complex stenosis (arrowhead). C: Angioplasty of the main renal artery
was performed; it also indirectly stretched the ventral branch stenosis (arrowhead). The
stenoses were improved but not normal. D: One year later all stenoses had remodeled
and the arteries were normal.
RENAL ARTERY STENOSIS IN THE PEDIATRIC AGE GROUP
The strategies for diagnosis of RAS in the pediatric age group are different from those in adult
disease. Pre-intervention MRA is usually not helpful and even CTA cannot adequately detect
branch stenoses. US is usually technically difficult in young children and not useful in branch
disease. Plasma renin activity (PRA) assumes a more important diagnostic role in identifying
children and infants with RVH.
Aortogram
Since the vessels of these patients are small, standard guide sheaths/catheters are frequently
too large. The femoral access can be via a 3-Fr flush catheter or through a 4-Fr sheath. The
renal artery can be catheterized with an appropriate 3- or 4-Fr mini visceral catheter (cobra,
Mini, or Baby versions of the Sos Omni Selective) through a femoral sheath, guide sheath, or
guide catheter no larger than 4 Fr. In these patients the aortogram is frequently negative since
there may only be branch RAS.
Selective Renal Arteriography

Since branch stenoses are frequently hidden on aortography, multiple selective and
subselective magnification oblique and caudocranial angulation arteriograms must be obtained
to find these stenoses.
Angioplasty
The diagnostic catheter can be used for test injections and selective arteriograms with a Touhy-
Borst Y connector over the wire if the diameter of the guide wire used to cross the stenosis is
smaller than the lumen and end hole of the catheter. Angioplasty can then be performed once
the location of the stenosis is documented with the guide wire in place just as described for
adult FMD earlier. Completion arteriogram is obtained by reintroducing the diagnostic catheter
with the Touhy-Borst Y connector over the guide wire. Angioplasty of focal weblike stenoses is
usually successful and requires short-duration, low-pressure inflations (Fig. 17-26). RAS due to
rare cases of developmental hypoplasia of the aorta and the renal artery, midaortic syndrome,
form a special subclass of lesions (93). In these cases there is usually hypoplasia of the
pararenal abdominal aorta and there are ostial RAS. The arteriographic appearance may be
similar to other arteridites, but the RAS behaves differently when angioplasty is attempted.
Much of the balloon in the stenosis expands fully except for a very resistant, thin, ringlike
constriction, usually at the aortic wall. Vigorous efforts to expand the balloon with high pressure
can result in catastrophic rupture of the renal artery. These lesions should be repaired by
surgery. Stents should not be used in children, as already discussed for FMD above (92).
RENAL TRANSPLANT ARTERIAL STENOSIS

Arteriography
These patients frequently present with hypertension and RI, therefore iodinated contrast must
be used sparingly as in the atheromatous patient. Knowledge of the location of the transplant
and the type of anastomosis will dictate the side of femoral puncture. Generally, hypogastric
end-to-end anastomoses are better approached via the contralateral femoral artery around the
aortic bifurcation, whereas end-to-side external iliac artery anastomoses are easier to access
via the ipsilateral femoral artery. If the distal aorta and the iliac arteries have not been
previously imaged by MRA or CTA, an aortic bifurcation arteriogram should first be performed
and pressures from the aorta to the site of anastomosis evaluated. An MRA, CTA, or duplex
US are helpful to establish the precise obliquity for arteriography to best demonstrate the
anastomosis. If one of these is not available, external iliac anastomoses should be studied in a
steep ipsilateral posterior oblique projection (the transplant anastomosis is usually
anterolateral) (Fig. 17-27); for a hypogastric anastomosis the proximal internal iliac artery
should be catheterized and an AP arteriogram obtained. The extra- and intrarenal circulation
should be completely evaluated, since branch stenoses, though rare, may be present. The
transplant renal artery should not be selectively catheterized until its exact position and status
and those of the anastomosis are known. Selective catheterization of the transplant renal artery
is performed by modifications of the techniques already described. The Mini and Baby versions
of the Sos Omni Selective or other visceral catheters such as the cobra can be used.
Angioplasty and Stenting

Prior to intervention the pressure gradient must be documented as in ARAS. Hypogastric end-
to-end anastomoses usually respond to angioplasty; stents are usually not necessary except
for restenoses and stenoses with immediate elastic recoil.
End-to-side stenoses respond similarly to ostial ARAS and frequently require stents as the
primary treatment (Fig. 17-27). Anastomotic kinks are difficult to evaluate by pressure
measurement because the catheter or wire across them tends to straighten out the kink and
eliminate the gradient. The best way to document a gradient across a kink is through a very
soft and flexible thin microcatheter.
COMPLICATIONS AND THEIR AVOIDANCE

Contrast Nephropathy
Iodinated contrast-induced nephropathy or acute renal failure is reported to occur in 1% to 6%
of cases (94,95), and in up to 40% to 50% of diabetics with already compromised renal
function (96, 97, 98). Fenoldopam does not have a renal protective benefit in high-risk patients
(98). Acetylcysteine is inexpensive, is easy to use, has no known serious side effects at the
recommended doses, and has been shown to have some benefit, therefore it can be used in
appropriate patients (73,74). Using hydration with sodium bicarbonate and iodinated contrast
sparing techniques as described earlier, under Techniques, is the best way to avoid transient or
permanent contrast-induced nephropathy (100).
Microcholesterol Embolization
Manipulations in the atheromatous aorta and renal arteries can produce cholesterol
microembolization, the most feared and least preventable complication of renal artery
intervention. This complication is underrecognized and underreported as occurring in ~3% of
renal artery interventions. The
clinical manifestations of cholesterol microembolization are related to the amount and size of
the particles and the location of the end arteries they occlude. Patients present with peripheral
eosinophilia, splinter hemorrhages in the toes, livedo reticularis, and acute renal failure, which
usually begins 1 week after intervention and inexorably progresses to RI (100). Three have
been anecdotal cases of some recovery of function and of improvement following treatment
with corticosteroids (101,102). Although several embolic protection devices are being fiercely
advocated and used for renal artery stenting, their efficacy is not proven. Embolic protection
devices were designed for the carotid arteries, therefore their deployment in the renal arteries
is not as safe or secure as it is in the carotid arteries. Additionally, renal cholesterol emboli can
shower not only from the renal arteries but also, during attempted catheterization of the renal
artery, from the frequently very atheromatous abdominal aorta; even if the protection devices
once deployed in the renal arteries were 100% effective, they could not prevent embolization
prior to their deployment. The pore size of the typical filter-type designs is 100 m, which is
inadequate to filter most significant cholesterol microemboli, which are smaller. The significance
of this problem was confirmed by an elegant ex vivo study demonstrating that during typical
manipulations in ARAS, millions of emboli <10 m, but only a few (four or five) particles 1 mm,
were produced (103). Occlusion balloon-type designs minimize this problem but produce warm
renal ischemia while inflated, and all the debris must be evacuated or flushed away from the
renal artery. There are only a handful of reports on the use of protection devices. These series
include small numbers of patients and most use flawed technique during intervention or their
results are not statistically different from previous preprotection data reported by the same
authors. (This is discussed in more detail under Results, below.)
FIGURE 17-26. The need for selective and subselective arteriography in multiple obliquties
and caudocranial angulations in RAS in children. Focal RAS of uncertain etiology in a 4-
year-old girl with severe hypertension and elevated PRA. A: Initially the aortogram was
thought to be normal, but careful inspection revealed some bumpy irregularity in the
region distal to the branching of the left main renal artery (arrowhead). B-E: Multiple
selective left renal arteriograms in different obliquties and caudocranial angulations did not
further define the abnormality (arrowhead). F: Only a subselective upper pole branch
injection demonstated a focal severe weblike stenosis (arrowhead) with pre- and
poststenotic dilatation (which produced the abnormality seen on the aortogram). G: The
stenosis was successfully treated with a 2-mm angioplasty and the child became
normotensive.
Mechanical Complications
During passage of catheters and guide wires through the atheromatous aorta and renal arteries
for angioplasty and stent deployment, the artery can go into spasm or be occluded, perforated,
dissected, or ruptured. Intrarenal or distal macroemboli, in situ thrombosis, or
thromboembolism from areas of manipulation and puncture site injury can also occur (104).
These
complications are all rare; each occurs in <1% of cases. Meticulous techniques as described
above and improved equipment minimize the frequency and severity of complications, and most
are pharmacologically reversible or can be treated by interventional techniques such as
redilatation, stent deployment, and fibrinolysis.
FIGURE 17-27. End-to-side renal transplant artery to an external iliac artery stenosis in a
severely hypertensive patient. A: Pre-intervention a severe proximal RAS (arrow) is
identified with a 75 mm Hg gradient. B: Poststent the vessel is wide open (arrow) and the
gradient has been eliminated. The patient is only mildly hypertensive on fewer medications.
RESULTS
The technical success of intervention for all forms of RAS is currently well over 90%.
Restenosis occurs in 15% to 20% of renal artery stents and can be retreated by percutaneous
techniques as described in detail under Techniques, above.
The data on benefits of intervention for hypertension are convincing in FMD (Table 17-4) (105,
106, 107, 108, 109, 110) and in infants and children (111) and arteridites (112,113), where
there are fewer confounding variables than in ARAS.
Although there are short- to medium-term benefits for hypertension and RI in renal transplant
arterial stenosis, intervention may not extend graft survival (12). The blood pressure benefits for
interventional treatment of RVH due to ARAS are in the 60% to 70% range, though cures are
rare (Table 17-5) (105,107,110,114, 115, 116, 117, 118, 119, 120), and in many cases of
reported improvement it is difficult to separate the effects of the intervention from those of
improved medical therapy, which can be accomplished with a reduced number of but more
effective drugs.
TABLE 17-4 RESULTS OF RENAL ARTERY ANGIOPLASTY FOR RENAL

VASCULAR HYPERTENSION IN FIBRROMUSCULAR DYSPLASIA
First author (ref Patients, Technical success, Cured, n Improved, n Follow-up mo, mean
no.) N n (%) (%) (%) (range)
16
Sos (105) 31 27 (87%) 9 (33%) 16 (4-40)
(59%)
Tegtmeyer 26 39
66 66 (100%) na (2-121)
(106) (37%) (59%)
Geyskes 10
21 21 (100%) 9 (43%) na (12-48)
(107) (48%)
Martin L 5 12
20 20 (100%) 16 (3-36)
(108) (25%) (60%)
Martin E 5
11 8 (73%) 1 (13%) 13 (na)
(109) (63%)
5
Grim (110) 10 9 (90%) 4 (44%) 10 (1-14)
(56%)
67 74
Total 159 151 (95%)
(45%) (48%)
Note. na, not applicable.
There are significant differences between interventionalists and internists regarding the
perceived benefits of intervention for RI in patients with ARAS. CORAL, a prospective
randomized study, was organized to evaluate and compare the benefits of optimal medical
therapy alone to intervention and optimal medical therapy in patients with ARAS and RI
(118,119). Proponents of conservative therapy for ARAS argue that most MACEs in patients
with ARAS occur as a result of coexistent cardiovascular disease; that ESRD due to RAS,
which does have a very high rate of MACE, occurs rarely; and that there is little support in the
literature for the benefits of renal artery intervention compared to aggressive medical therapy to
prolong life and avoid MACE (119). The DRASTIC study, which is often cited to support
arguments against intervention, concluded that there was no benefit of renal angioplasty
compared to medical therapy (121). Ironically, the raw data prove the opposite: patients
treated with angioplasty had significantly better blood pressure control on fewer drugs, and a
lower incidence of RI, than the medical group. The cause of the different interpretation of the
results was that 44% of the medical group
failed therapy and were crossed over to angioplasty but were analyzed as part of the medical
group. The results of intervention were also suboptimal because many ostial ARAS lesions
were treated with angioplasty, not stents, which is the current standard of care.
TABLE 17-5 RESULTS OF ANGIOPLASTY OF ATHEROSCLEROTIC

RENAL ARTERY STENOSIS (ARAS) FOR RENAL VASCULAR
HYPERTENSION; MANY OF THESE PATIENTS HAD OSTIAL ARAS BUT
WERE NOT SEPARATELY REPORTED
First author (ref. no.) Patients (n) Benefit (%) Cure (%) Improve (%) Failed (%)
Tegtmeyer (114) 65 94 23 71 6
Schwarten (115) 52 92 44 48 8
Klinge (116) 133 78 10 68 22
Martin (117) 204 63 16 47 37
Baert (118) 141 61 28 33 39
Geyskes (107) 44 52 9 43 48
Miller (119) 46 50 13 37 50
Canzanello (120) 100 43 4 36 60
Grim (110) 25 40 4 36 60
Sos (105) 51 33 15 18 67
Total 1031 64 17 47 36
The results for intervention for ARAS in patients with RI are encouraging, but even in this group
intervention must be undertaken with some caution since most series report a 15% to 20%
incidence of deterioration of preintervention renal function without the use of protection devices.
A meta-analysis of several hundred patients with SCr 1.5 mg/dL shows the following results:
28% (range, 19% to 43%) were improved, 44% (range, 29% to 67%) were stable, and 28%
(range, 4% to 32%) were worse following intervention without embolic protection (Table 17-6)
(122, 123, 124, 125, 126, 127, 128, 129, 130, 131). These data are difficult to compare
because most authors use different criteria for selection and evaluation.
The results for stents in subsets of patients with RI of different severities are reported in Table
17-7. Some recent small series that utilized embolic protection devices report even better
improvement or preservation of renal function, but most have some technical and
methodological issues that may call their results into question. Henry reported two small series
using a protection device in 23 patients (13 with RI) in 2001 (132) and in 56 patients (18 with
RI) in 2003 (133); in these series (which may include some of the same patients) no patient had
deterioration of renal function, but the results are not statistically different from those of a much
larger 1999 series by the same author without using a protection device, where in 210 patients
(48 with RI), renal function was improved in 29% (14 of 48), unchanged in 67% (32 of 48), and
worse in only 4% of patients (128). In 2003 Holden et al. reported a series of 37 patients with
RI (46 arteries) using a protection device; renal function was improved in 38%, was stable in
57%, continued to decline in 5%, and none had acute deterioration (134). The ARAS were first
crossed with an 8-Fr guide catheter (9-Fr or 2.7-mm outer diameter) prior to deployment of the
filter. This techniqueessentially the same as not using a protection deviceis virtually certain
to result in significant cholesterol embolization. It is therefore difficult to understand how these
excellent results were obtained with such a crude technique and to reconcile them with the
statistically identical results reported by the same author in 2006 using a much lower-profile
system to deploy the protection device in 63 patients (83 arteries), where 40% improved, 57%
were stable, and 3% had continually declined renal function (135). The only publication using
renal protection without apparent flaws was a small series by Edwards et al. in 2006 (136).
They reported on 32 patients, 24 with RI; renal function improved in 52% and deteriorated in
none. However, at up to 1-year follow-up, four
(31%) whose renal function had initially improved showed deterioration of renal function to
preoperative levels or worse at 4 to 6 months, three of them due to restenosis, and two had
repeated benefit, with improvement in renal function after re-intervention.
TABLE 17-6 RESULTS OF ATHEROSCLEROTIC RENAL ARTERY

STENTING WITHOUT PROTECTION FOR RENAL INSUFFICIENCY
SCr (% of patients)
No. patients with SCr 1.5
Patients mg/dL Follow-
First author (ref. no.) Improved Stable Worse
(n) up (mo)
Dorros (122) 163 91 40 29 31 6
Burket (123) 127 37 43 24 32 15
Boisclair (124) 33 17 41 35 24 13
Bloch (Sos)
89 62 26 53 20 24
(125)
Harden (126) 32 32 34 34 28 8
Rundback
45 45 25 43 32 17
(127)
Henry (128) 210 48 29 67 4 25
Rocha-Sing
132 71 28 59 13 13
(129)
Gill (130) 100 65 31 42 31 25
Lederman
300 101 19 54 27 16
(131)
Total 799 609 28 44 28 6-25
Note. SCr, serum creatinine.
TABLE 17-7 RESULTS OF ATHEROSCLEROTIC RENAL ARTERY

STENTING WITHOUT PROTECTION IN SUBSETS OF PATIENTS WITH
RENAL INSUFFICIENCY AT NYPH WCC
Renal SCr 1.5 mg/dL SCr 1.6 mg/dL SCr 1.6-2 mg/dL SCr 2.1-4 mg/dL SCr >4.1 mg/dL
function (N = 24) (N = 50) (N = 25) (N = 15) <(N = 10)
Improved 15 (30%) 6 (24%) 4 (27%) 5 (50%)
Stable 21 (88%) 24 (48%) 15 (60%) 7 (46%) 2 (20%)
Worse 3 (12%) 11 (22%) 4 (16%) 4 (27%) 3 (30%)

Note. SCr, serum creatinine.
Protection devices, if they worked, would be an important addition to the safety of renal artery
intervention, but there is no level 1 scientific evidence to support their efficacy at this time.
CONCLUSION
In carefully selected patients with physiologically significant RAS, renal artery angioplasty and
stenting are the treatments of choice for renal dysfunction, poorly controlled hypertension, or
recurrent pulmonary edema and other cardiac disturbance syndromes. There is no evidence,
however, that prophylactic stenting of mild to moderate, physiologically nonsignificant, and
clinically asymptomatic renal artery stenoses (especially if clinically not fully evaluated) has any
benefit compared to aggressive medical therapy and lifestyle changes to prevent progression
and the clinical sequelae of renal failure, hypertension, and decreased longevity. Statins and
risk reduction are the new paradigm for the treatment of all atheroma, especially when clinically
and hemodynamically not significant, but also for the treatment of clinically and physiologically
significant stenoses following interventional treatment.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 18 - Upper Extremity Arterial
Revascularization
Chapter 18
Upper Extremity Arterial Revascularization
Malcolm K. Sydnor
Daniel A. Leung
Of patients presenting with symptoms of extremity ischemia, <5% involve the upper limbs (1).
The majority of these cases are secondary to vasospastic disorders such as Raynaud's
syndrome and small vessel occlusive disease (2,3). Although the incidence of symptomatic
upper extremity occlusive disease is low compared with that of the lower extremities, the list of
potential etiologies is relatively long and is provided in Table 18-1. Most of these conditions are
treated medically, though some patients may be candidates for surgical procedures such as
bypass or sympathectomy. Among patients presenting with chronic large vessel upper
extremity occlusive disease, the most common cause by far is atherosclerotic disease (4, 5, 6).
The incidence of atherosclerotic subclavian stenosis in the general population is reported to be
approximately 1% (7). In one large study, 17% of patients undergoing arch aortography had
innominate or subclavian lesions of 30% (8). In another study, 12% to 15% of patients
undergoing cerebral angiography were found to have subclavian lesions, with angiographic
subclavian steal demonstrated in 2% to 3% (9). Consequently, proximal atherosclerotic disease
represents the largest subset of patients who present for upper extremity revascularization.
The next most common causes are Takayasu arteritis and radiation-induced occlusive disease
(5), with thoracic outlet syndrome, giant cell arteritis, fibromuscular dysplasia, and exclusion for
thoracic aortic stent-graft placement rounding out the list of etiologies of proximal occlusive
disease.
The surgical literature is abundant with reports of successful revascularization, particularly since
the advent of extrathoracic repair in the 1950 s and 1960 s (10,11). Since the first reported
subclavian angioplasty in 1980 (12), percutaneous endovascular techniques have made great
strides in both efficacy and acceptance such that, at many institutions today, endovascular
treatment has largely supplanted surgery as the treatment of choice for proximal upper
extremity occlusive disease. This chapter presents the indications for and techniques of upper
extremity endovascular therapies and reviews their results and patency rates. In addition,
treatment of acute upper extremity occlusive disease including trauma and embolic disease is
discussed later in the chapter, as are nonatherosclerotic causes of chronic occlusive disease.
DEMOGRAPHICS AND PRESENTATION

Atherosclerosis is the underlying cause in the vast majority of patients who present with chronic
symptoms of proximal upper extremity ischemia. Most patients with atherosclerotic lesions of
the innominate or subclavian arteries are asymptomatic because of the rich supply of
brachiocephalic collaterals. Approximately 70% of the lesions occur on the left and they tend to
be proximal to the origins of the internal mammary and vertebral arteries (9). Multiple stenoses
are present in 35% to 85% of patients including concomitant subclavian and carotid lesions.
This process tends to occur in younger patients (mean and median ages of 50 to 57 years) with
atherosclerotic disease affecting other areas and it demonstrates a slight male predominance
(51% to 55%). Smoking, which is the most important risk factor, is present in 75% of patients.
Coronary artery disease is present in 27% to 65% of patients (5,13, 14, 15, 16, 17). Diabetes
tends to be less prevalent in this population, suggesting that these patients represent a
separate subgroup of atherosclerotic disease. In one study, synchronous lower extremity
disease was present in 48% of cases but only 1.2% of patients with lower extremity occlusive
disease also had upper extremity disease (18).
There are a number of clinical presentations for upper extremity ischemic disease (Table 18-2).
Subclavian steal syndrome was first reported in 1961 and occurs when there is a stenotic or
occlusive subclavian or innominate lesion and blood is siphoned into the ipsilateral arm (19,20)
(Fig. 18-1). Despite flow reversal in the ipsilateral vertebral artery, most patients remain
asymptomatic. With the rich supply of collaterals in this area, radiographic steal can occur
without clinical steal, depending on the patency of the contralateral vertebral artery, basilar
artery, carotid arteries, and circle of Willis. When symptoms do develop, they are
vertebrobasilar in origin and often worsen with exercise or work of the ipsilateral upper
extremity. Symptoms are those of transient ischemic attacks and include vertigo, syncope,
ataxia, visual disturbances, dysphasia, paresthesia, dysarthria, and motor deficits (21, 22, 23,
24, 25, 26, 27). Ipsilateral upper extremity arm claudication from subclavian or innominate
occlusive disease may occur independently or coexist with symptoms of subclavian steal.
Together, they represent the two most common clinical presentations (28, 29, 30, 31, 32, 33,
34, 35). In patients who have undergone coronary artery bypass surgery, proximal upper
extremity occlusive disease may present as coronary-subclavian steal (Fig. 18-1). The internal
mammary arteries, particularly the left, are usually the first choice as a conduit for coronary
bypass surgery. When a subclavian lesion is present, flow to the graft may become
compromised, leading to angina or myocardial infarction (36, 37, 38, 39, 40, 41, 42, 43, 44, 45,
46, 47, 48). Proximal upper extremity atherosclerotic occlusive disease can also present with
digital ischemia due to embolic disease from subclavian or innominate atheromatous plaque
with or without aneurysmal disease (49).
Other patients may present with poorly functioning dialysis fistulas or axillary-distal bypasses
from subclavian or innominate inflow disease. Alternatively, patients may be asymptomatic and
present with incidental findings on physical exam or imaging studies.
CLINICAL EVALUATION
Important findings in the history and physical examination of patients with proximal upper
extremity occlusive disease are
summarized in Table 18-3. The physical examination should include palpation and auscultation
of the upper extremity pulses, carotid pulses, and superficial temporal pulses. Bruits or
diminished pulses suggest a proximal lesion. Bilateral upper extremity brachial artery blood
pressure measurements should be obtained. A blood pressure differential of >20 mm Hg
systolic suggests the presence of a significant unilateral lesion (50). If bilateral lesions are
present, both upper extremity blood pressures may be low, and they should be compared to
lower extremity blood pressures.
TABLE 18-1 ETIOLOGIES OF UPPER EXTREMITY ISCHEMIA
Acute ischemia
Trauma (blunt, penetrating, iatrogenic [(ABG/catheterization])
Embolic disease (heart, AVF, upstream aneurysms, or occlusive disease)
Chronic distal ischemia
Vasospastic disorders (e. g., Raynaud's disease)
Autoimmune disorders (e. g., scleroderma, SLE, Sjgren syndrome, RA, CREST
syndrome, polymyositis or dermatomyositis, mixed connective tissue disease)
Buerger's disease (thromboangiitis obliterans)
Blood dyscrasias (cold agglutinins, cryoglobulins, myeloproliferative diseases)
Drug-induced occlusions (medical including ergotamines and recreational including

cocaine, amphetamines, Cannabis)
Occupational trauma
Chronic proximal ischemia
Atherosclerosis
Aneurysmal disease
Takayasu arteritis
Radiation-induced occlusive disease
Fibromuscular dysplasia
Thoracic outlet syndrome
Thoracic stent graft exclusion of subclavian artery (often intentional)
TABLE 18-2 CLINICAL PRESENTATIONS OF PROXIMAL UPPER

EXTREMITY OCCLUSIVE DISEASE
Vertebrobasilar symptoms (subclavian steal)
Upper extremity claudication
Coronary-subclavian steal
Upper extremity embolic disease
Leg claudication in patients with axillofemoral bypass grafting
Poorly functioning dialysis fistulas in patients with upper extremity fistulas or grafts
Upper extremity rest pain or tissue loss (usually postembolic or posttraumatic)
Incidental on clinical examination (blood pressure gradients, bruits, diminished pulses)
Incidental on imaging studies (ultrasound, CTA, MRA)
Claudication after thoracic stent graft occlusion of subclavian artery

Obtaining brachial-wrist indexes and pulse volume recordings in the noninvasive vascular
laboratory can also serve as a helpful adjunct for diagnosis. As in the lower extremity, triphasic
waveforms are encountered in the normal patient and dampened or monophasic waveforms
suggest upstream obstructions. Wrist brachial indexes <0.85 to 0.7 should be considered
abnormal in the upper extremity (51,52). Further noninvasive evaluation can be performed with
ultrasound, computed tomography (CT) angiography (CTA), or magnetic resonance (MR)
angriography (MRA)..
Duplex scanning can identify stenoses and occlusions in the subclavian and upper extremity
arteries. Lesions in the retroclavicular portions of the subclavian artery are difficult to visualize
but may be inferred from abnormal waveforms and flow acceleration. Lesions in the supra-
aortic trunk vessels are not well visualized with ultrasound but can be evaluated with CTA or
MRA.
In patients with normal renal function, CTA with multidetector helical scanners to obtain thin
section axial images can provide valuable diagnostic information of the arch vessels or upper
extremities. This is best performed by using automated bolus detection and scan triggering (e.
g., SmartPrep [GE Medical Systems] and CareBolus [Siemens]) during the arterial passage of
dynamically administered intravenous contrast at a rate of 3 to 4 mL/second. The injection
should be performed through the extremity of least interest to avoid venous contamination and
artifact. The arms should also be raised above the head to reduce streak artifact from the
body. Images are best reviewed at a three-dimensional (3D) workstation using multiplanar
reformations and maximum intensity projections (53) (Fig. 18-2).
Three-dimensional gadolinium-enhanced MRA is also an excellent modality to image the arch
and upper extremity arteries. While technically more challenging than CTA, MRA does not
require iodinated contrast or expose the patient to ionizing radiation. The study can be
performed with a 0.2 mmol/kg injection of Gd-chelate followed by a 20- to 30-mL saline flush
through a vein in the extremity of least interest. As with CTA, the timing of the bolus is a critical
factor. This can be achieved by using a test bolus, an automated bolus detection algorithm, or
an MR fluoroscopic trigger. The aortic arch and proximal arch vessels are best visualized in the
sagittal oblique and coronal planes (54). Depending on the coverage and spatial resolution
desired, a second injection with dedicated peripheral imaging may be necessary. MRA does
have the advantage over CTA of being easier to reconstruct on a 3D workstation, without the
difficulties posed by chunky calcifications. Nonetheless, both techniques tend to overestimate
the degree of stenotic lesions.
Digital subtraction angiography remains the diagnostic gold standard but is often reserved for
complex cases, preoperative planning, or pre-endovascular therapy. Optimal angiography
includes an arch aortogram as well as a four-vessel cerebral arteriogram. Special attention
should be focused on the origins of the supra-aortic vessels, the presence of arch or circle of
Willis anomalies, and delayed imaging to evaluate for reconstitution of proximally occluded
vessels from the steal phenomenon. When planning proximal revascularization, an upper
extremity runoff may also be performed to evaluate for preexisting downstream pathology.
SURGICAL REVASCULARIZATION
Early transthoracic repair of aortic branch vessel occlusive disease carried mortality rates of
15% to 20% (55,56). While innominate artery lesions usually still require a transthoracic
approach (57,58), the advent of extrathoracic repair for subclavian disease over the last four
decades has significantly
improved surgical outcomes. Extrathoracic procedures avoid the need for a median sternotomy
and cardiopulmonary bypass and include subclavian-to-subclavian bypass, axillo-axillary
bypass, carotid to subclavian bypass, and subclavian-carotid transposition.
FIGURE 18-1. A 72- year-old patient status post-coronary artery bypass graft with
suspected coronary steal. Early (A)- and late (B)-phase images from arch aortogram
demonstrate proximal subclavian occlusion (arrow) with reconstitution via retrograde flow in
the vertebral artery and IMA (arrow). C: DSA image following recanalization prior to stent
deployment. Note protective catheter and guide wire in IMA. D: Completion angiogram
following stent placement with antegrade flow in the vertebral artery and IMA.
Axillo-axillary bypasses, using PTFE or Dacron, are often employed in high-risk patients with
major comorbidities including coronary-subclavian steal. While exposure can be performed with
local anesthesia, they have lower primary patency rates and inherent risks including skin
erosion and distal embolization (59,60). Subclavian-to-subclavian bypasses are reserved for
unique situations.
Subclavian-carotid transposition is the preferred surgical technique due to superior patency
rates (61, 62, 63, 64). It is usually performed by ligation of the subclavian artery with a
subsequent end-to-side anastomosis to the carotid artery. However, this procedure is reserved
for patients with close proximity of the carotid artery to the subclavian artery, when the
occlusive disease is limited to the proximal segment of the subclavian artery, and when the
common carotid artery does not contain significant disease. In cases where transposition is not
possible, carotid-to-subclavian bypass can be performed using a 6- or 8-mm PTFE prosthesis
from the carotid artery to the subclavian artery beyond the vertebral and internal mammary
artery origins. This allows for a technically easier exposure than the transposition procedure
(59).
Results, including long-term follow-up, are well described in the literature. Hadjipetrou et al.
(65) reviewed the surgical literature from 1972 to 1998. From 1988 to 1998, the technical
success was 96%, with a 10-year primary patency rate (based
largely on clinical findings) of 88%. Complications occurred in 13%, including stroke in 3% and
death in 2% (23,66, 67, 68, 69, 70, 71, 72, 73, 74, 75). In 2001, Kandarpa et al. (76) reviewed
the five most recent surgical series with 50 patients and found similar results: technical
success in 99% and 5.5-year symptomatic recurrence in 10%, with total complications reported
in 19%, including a 3% stroke rate and 3% mortality rate (23,63,64,77,78).
TABLE 18-3 KEY HISTORY AND PHYSICAL EXAMINATION FINDINGS IN

PATIENTS WITH PROXIMAL UPPER EXTREMITY ARTERIAL OCCLUSIVE
DISEASE
History Physical examination
Cerebral vascular accident Diminished pulses
Transient ischemic attack Subclavian or carotid bruits
Syncope Induced upper extremity claudication
>20 mm Hg upper extremity blood

Ataxia
pressure gradient
Visual disturbances Fingertip discoloration or ulceration
Upper extremity claudication Subungual hemorrhages

Rest pain or tissue loss Livedo reticularis
Angina with prior IMA bypass Muscle atrophy
Lower extremity ischemia with prior

axillary- distal bypass
Poorly functioning dialysis fistula
FIGURE 18-2. A 25-year-old patient suffered a gunshot wound to the right upper chest.
Axial (A) and volume-rendered three-dimensional (B, C) CT images show right subclavian
artery pseudoaneurysm (arrows) to good advantage compared with conventional DSA in
AP projection (D). Note the high-density bullet (arrow) anterior to the subclavian
pseudoaneurysm.
PERCUTANEOUS REVASCULARIZATION
The first subclavian artery angioplasty was reported by Bachman and Kim in 1980 (12). This
was followed over the next 15 years by many other promising reports of brachiocephalic and
subclavian angioplasty (79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96,
97, 98, 99). With the advent of percutaneous stenting in the early 1990s, it became possible to
treat a wider variety of lesions, including occluded vessels. Hadjipetrou et al. (65) summarized
the 108 stents reported in seven studies over the late 1990 s and found a technical success
rate of 97% with 6% minor complications and no strokes or mortalities. There was a 3%
recurrence rate with a mean follow-up of 20 months (24,32,100, 101, 102, 103).
In 2001, Kandarpa et al. (76) analyzed the five most recent series with >50 patients. Because
of the lengthy period it took to accumulate this many patients, many of the lesions were treated
before the common use of stents. Ninety percent of these patients were treated with
angioplasty alone and there was no significant difference in outcome between those treated
with stents and those treated with PTA alone. The technical success rate was 46% for
occlusions and 98% for stenoses. The mortality and stroke rates (<0.5%) were minimal; there
were no reported upper extremity embolic episodes. The recurrence rates were 9% for
occlusions at 37 months and 11% for stenoses at 63 months (32,34,94,97,104).
Despite early evidence that stenting may not significantly improve the long-term results of
angioplasty alone, most recent authors have employed the routine use of stents, especially
when treating aortic ostial lesions and occlusions (30,33,105, 106, 107). Primary stenting has
been advocated by some (30,106,107) for several theoretical advantages, such as
improvement of patency rates by eliminating acute vessel closure from dissection. This has
been shown to be the case in other large vessels including the iliac and carotid arteries
(108,109). Additionally, embolic complications may be reduced by compressing plaque material
between the stent and the arterial wall (30,106,107). Amor et al. (107) compared subgroups of
patients in a series of 89 subclavian lesions. The group that underwent predilatation prior to
stenting had a restenosis rate of 28.5%, while the group that underwent primary stenting had
decreased acute complications and a restenosis rate of 4.7%. Brountzos et al. (30) recently
reported a cumulative primary patency rate of 77% at 24 months and a cumulative secondary
patency rate of 91.7% in 48 patients who underwent primary stenting of subclavian and
innominate lesions. Complication rates were similar to those in other studies. These results led
the authors to recommend primary stenting as the treatment of choice. However, this
recommendation may be disputed by some with regard to nonostial lesions, where angioplasty
alone still has several advantages including lower cost and not leaving a foreign body in the
patient. The role of covered stents and their potential advantages with respect to patency and
embolic protection remain to be evaluated in systematic fashion.
Although there is still a paucity of long-term patency data, endovascular results are promising
and offer many advantages over surgery including decreased length of hospital stay, morbidity,
and mortality. Patency rates are similar, repeat endovascular therapy can result in excellent
long-term assisted primary patency rates, and a percutaneous intervention does not preclude
later surgery. In addition, percutaneous therapy is particularly beneficial in patients with multiple
comorbidities as the risks of a cervical incision and general anesthesia can be avoided. Certain
patients, including those with thrombophilia, renal insufficiency, and rheumatoid arthritis, have
been shown to have higher major complication rates during surgical great vessel
revascularization and may therefore experience additional benefit from endovascular therapy
(110).
Patient Selection and Technique

Symptomatic vertebrobasilar insufficiency and/or lifestyle-limiting upper extremity claudication
due to atherosclerotic disease are historically the most common indications for percutaneous
revascularization. Treatment of severe asymptomatic lesions should also be considered,
particularly in younger patients who may ultimately undergo an internal mammary artery (IMA)
bypass or for bilateral lesions in order to monitor and treat hypertension (111). Less common
indications for treatment include distal embolic disease (Fig. 18-3), coronary-subclavian steal,
and protection of axillary-distal bypasses and arteriovenous fistulae.
Unusual potential indications for angioplasty and stenting include iatrogenic injury (112), for
symptomatic stenosis of an aberrant right subclavian artery (113), and for coronary access in
patients with occlusive disease involving all four limbs (114).
Patients with lesions secondary to giant cell arteritis or active Takayasu's arteritis should not
undergo endovascular treatment primarily, as they often improve after administration of
corticosteroid therapy. Thoracic outlet syndrome is due to extravascular causes and usually
requires primary surgical treatment (6).
Once the decision has been made to perform a percutaneous intervention, the normal
preprocedure laboratory values including prothrombin time, INR, and creatinine should be
obtained. All of our patients with renal dysfunction receive a bicarbonate drip to reduce the risk
of contrast-induced nephrotoxicity. Bilateral upper extremity preprocedure blood pressures
should be obtained. Although some groups choose to puncture the ipsilateral brachial artery
(103,115), we access the common femoral artery whenever possible to avoid brachial sheath
complications. When the creatinine is normal, a digital subtraction angiography (DSA) arch
aortogram in the LAO projection is performed to establish the great vessel anatomy followed
by cerebral angiography to establish the circle of Willis anatomy and the presence of
retrograde vertebral flow. Alternatively, a preprocedure MRA of the arch and/or Circle of Willis
can be obtained. We routinely give a 5000 IU bolus of heparin prior to catheterizing the
diseased vessel. Any catheter manipulation in the aortic arch and great vessels should be
considered a neurointerventional procedure and great care, including double flushing, should be
taken to avoid introducing air or disrupting plaque and causing distal embolization.
Endovascular treatment of the proximal great vessels is typically performed through a 6- or 7-
Fr sheath, such as a 70-to 90-cm Raabe or a Shuttle sheath (Cook Inc., Bloomington, IN) using
a 0.035-in. guide-wire platform. The innominate and subclavian arteries can usually be
catheterized with a neurointerventional catheter such as a DAV (Cook Inc., Bloomington, IN) or
JB1 (Boston Scientific Corp., Maple Grove, MN). Depending on the orientation of the aortic
arch, a reverse curve catheter such as a Simmons (Cook Inc., Bloomington, IN) may be
required. This is particularly true for the brachiocephalic and right subclavian arteries in a type 2
or 3 aortic arch. Indeed, the endovascular treatment of the brachiocephalic or right subclavian
artery harbors a far greater level of complexity then that of the left subclavian artery, which is
relatively straightforward. For this reason, as well as the higher incidence of left-sided disease,
percutaneous treatment of the left subclavian is far more common than that of the right.
After crossing an obstructive lesion with a glide wire, the diagnostic catheter can usually be
advanced through the lesion into the distal subclavian artery. Tight stenoses or occlusions may
require a low-profile hydrophilic catheter such as a 4-Fr glide catheter (Boston Scientific Corp.,
Maple Grove, MN). Alternatively, the lesion can be crossed with a 0.018- or 0.014- in. guide
wire and low-profile balloon catheter. Occlusions are best traversed using a 0.035-in. angled
glide wire intraluminally. If subintimal recanalization is attempted, care should be taken to
reenter the distal lumen proximal to the origins of the vertebral and internal mammary arteries
to avoid compromising these vessels. Distal re-entry devices, such as the Outback (Cordis, A
J&J Company, Warren, NJ) or Pioneer (Medtronic, Santa Rosa, CA) catheters may be helpful.
Occasionally, retrograde catheterization from the brachial artery is necessary because of
vessel tortuosity or to cross a tough occlusion. In rare instances, a flossing guide wire may
need to be passed from
the groin access out of the brachial access to allow maximum pushability through the lesion.
FIGURE 18-3. A 46-year-old female with blue distal fifth digit of the right hand. LAO arch
aortogram (A) and selective right subclavian arteriogram (B) demonstrate severe axillary
artery stenosis (arrows). C: Magnified hand arteriogram shows perfusion defect involving
the distal fifth digit (arrow). D: Spot film during PTA demonstrates balloon waist as well as
SPIDERX (ev3) embolic protection device (arrow). E: Completion angiogram following
placement of Viabahn (Gore)-covered stent. Note embolic debris (arrow) within the
protection device.
In borderline stenoses, any concerns regarding lesion significance can be resolved by obtaining
a simultaneous translesion pressure gradient. If a 0.035-in. platform is chosen, the glide wire
should be exchanged for a stiff Teflon-coated guide wire prior to angioplasty and stenting.
There are a multitude of balloon catheters on the market, but we favor a noncompliant balloon
such as the Ultrathin Diamond (Boston Scientific Corp., Maple Grove, MN). Occasionally,
angioplasty alone results in an excellent angiographic result and stenting may not be necessary
(Fig. 18-4). Nonetheless, in today's practice, most lesions are stented regardless of the
angioplasty result. This is particularly true of ostial lesions and occlusions. Calcified proximal
lesions are often best treated with balloon expandable stents such as the Express LD (Boston
Scientific Corp., Maple Grove, MN) or Genesis (Cordis, A J&J Company, Warren, NJ), which
allow for precise placement 1 to 3 mm into the aorta, ensuring coverage of the ostium. Great
care should also be taken not to cover the right common carotid artery while stenting the
innominate artery and not to cover the vertebral or IMA supplying a coronary bypass when
stenting a subclavian artery. Balloon-expandable stents allow for precise placement. On the
other hand, postvertebral lesions and some occlusions may be better treated with self-
expanding stents such as the Smart stent (Cordis; A J&J Company, Warren, NJ) or Protg
(EV3;
Plymouth, MN) for improved flexibility. Covered stents including the balloon-expandable ICAST
stent (Atrium Corp., Hudson, NH) or the self-expanding Fluency (Bard Inc., Tempe, AZ) and
Viabahn (Gore Inc., Flagstaff, AZ) stents should be considered for aneurysmal disease or
irregular lesions that have a higher likelihood to cause vertebral or upper extremity emboli.
FIGURE 18-4. A 64-year-old golfer with left arm claudication. A: Left subclavian
arteriogram demonstrates moderate stenosis of the left subclavian artery (arrow)
extending to the left vertebral artery origin. B: Completion angiogram following PTA
demonstrates satisfactory angiographic result. Note protection wire within the vertebral
artery (arrow).
Distal protection devices are not routinely used for subclavian revascularization. Unlike carotid
lesions, one study found no new cerebral hyperintensities on diffusion-weighted MRI after
treatment of subclavian lesions (116), possibly because flow is typically reversed in the
ipsilateral vertebral artery. The situation is different, however, when treating the brachiocephalic
artery with a patent common and internal carotid artery downstream. In this instance, a distal
protection device such as the Filterwire EZ (Boston Scientific Corp.) or SPIDERX (EV3,
Plymouth, MN) can be placed into the internal carotid artery, while a second 0.018-in. guide
wire is placed into the subclavian artery or external carotid artery. A 0.035-in. stent can then be
advanced over both wires and deployed across the brachiocephalic artery during cerebral
protection.
After treatment, an angiogram is obtained through the sheath to document success and an
upper extremity or vertebral angiogram can be obtained if there is any question of embolic
complications. Typically, antegrade flow is seen in the ipsilateral vertebral artery after dilation of
the subclavian artery, but it has been shown that it may take up to 20 minutes or more for
cephalad flow to resume in the vertebral artery (27). We discharge most of our patients on
aspirin (250 mg PO q day) and plavix (75 mg PO q day for at least 4 weeks after a 300-mg PO
loading dose the night before or day of the procedure), and see the patients in follow-up at
approximately 1 month. Effective postprocedure surveillance can be achieved by following
clinical symptoms and upper extremity blood pressures.
Complications may be access site related and are the same as for other arterial procedures
including hematoma, pseudoaneurysm, or arteriovenous fistula formation. Abrupt vessel closure
of the treated vessel or embolic disease from the aortic arch and great vessels to the cerebral
or upper extremity arteries are also potential acute complications. Acute vessel dissection and
vessel rupture as well as cerebral hyperperfusion syndrome have also been reported (117).
Primary stenting and/or the use of protection devices may help to avoid embolic complications
and acute vessel closure and may improve acute patency rates. However, at least one study
has suggested less favorable long-term patency for stenting relative to angioplasty alone due to
in-stent restenosis (118). Stent fracture is another potential complication, particularly with
stents placed in the lateral aspect of the subclavian artery where the clavicle crosses the first
rib (119). Most complications, including vessel rupture, vessel dissection, distal embolization,
stent fracture, and restenosis, can be treated with percutaneous techniques.
REVASCULARIZATION OF ACUTE UPPER EXTREMITY

DISEASE
Acute upper extremity ischemia is more common than chronic upper extremity ischemia
(120,121), and of the acute causes, embolic disease, and trauma are by far the most frequent
(122). In these cases, patients tend to present with acute ischemia due to the absence of
collaterals and typically require urgent treatment.
REVASCULARIZATION OF ACUTE EMBOLIC DISEASE

Embolic disease to the upper extremities usually originates from the heart in association with
atrial fibrillation (122,123). Alternatively, the emboli may arise from upstream great vessel
atherosclerotic or aneurysmal disease or dialysis access sites (Fig. 18-3). Traditional therapy
has been surgical embolectomy with a Fogarty catheter, which has yielded excellent initial
results, but with complication rates approaching 20%, including 3% stroke rates and 3%
mortality rates (76,124). Success rates for transcatheter thrombolytic therapy approach those
of surgery for proximal embolic disease in the subclavian and axillary arteries, and for isolated
lesions in the brachial arteries, but have been reported as <0% for embolic disease below the
elbow (125, 126, 127, 128). Angiographic success is usually defined as at least one patent
vessel below the elbow with through line flow to the palmar arch while surgical success is
usually defined as clinical improvement. This at least in part explains the inferior thrombolysis
results for distal disease when compared to surgery.
Predictors of success for upper extremity transcatheter thrombolytic therapy include the
presence of proximal as opposed to distal disease and acute rather than chronic clot. Emboli
from the heart may be chronic and organized and, thus, difficult to lyse. In cases where
through-flow cannot be established with lytic therapy, surgical embolectomy may be required. In
addition to the usual major thrombolytic complication rate of 0% to 8% (129) including
hemorrhagic stroke of 1% to 2.3% (130), upper extremity therapy carries the additional
theoretical risk of pericatheter thrombosis leading to stroke.
Thrombolysis may also be performed for revascularization of acute upper extremity lesions due
to in situ thrombosis secondary to a variety of causes including atherosclerotic disease,
thoracic outlet syndrome, arteritis, and posttraumatic events (131, 132, 133, 134). Patients
usually present with acute onset of a cold and painful hand, progressing to loss of sensory and,
subsequently, motor function. Patients with preserved motor function (SVS/ISCVS categories I
and IIa) may be candidates for endovascular treatment or transcatheter thrombolysis. Patients
who have profound ischemia (SVS/ISCVS categories IIb and III) with paralysis and loss of
Doppler signals should be referred for emergent surgical thrombectomy. Duplex ultrasound
examination can be obtained quickly and may be useful to determine the level of obstruction
prior to treatment.
If percutaneous treatment is performed, the study should commence with an LAO arch
aortogram to evaluate great vessel anatomy and pathology, including potential sources of the
embolic disease. A neurangiographic catheter is then used to catheterize the subclavian artery
of the symptomatic limb and an upper extremity runoff is performed to evaluate the level and
extent of disease and the presence of variant vascular anatomy. In our experience, axillary and
brachial arteries are best treated by administering thrombolytic agents through a multisidehole
4- or 5-French infusion catheter such as the Unifuse catheter (Angiodynamics Inc., Queensbury,
NY). Our current infusion protocol consists of 1 mg of rt-PA per hour through the catheter and
low-dose heparin anticoagulation at approximately 500 U per hour through the groin sheath to
avoid perisheath and pericatheter thrombosis. The process may be accelerated with pulse
spray administration of rt-PA through the catheter before the infusion is initiated. Other groups
have had success with different concentrations of lytic infusion agents. One group has
successfully used a decreasing dose of rt-PA from 6 to 3 mg over the first hour, followed by 1
mg per hour over the next 7 hours, followed thereafter with 0.4 mg/hour (125). Patients are
usually re-evaluated with angiography approximately every 12 hours and thrombolysis typically
does not exceed 3 days due to the increasing risk of bleeding complications (130).
For more distal disease involving the arteries of the forearm and hand, a low-profile infusion
catheter can be used, such as a 3-Fr MicroMewissen catheter (EV3, Plymouth, MN).
Alternatively, an end-hole infusion can be performed through a 4- or 5-Fr catheter in the axillary
or brachial artery, which helps to avoid spasm. Occasionally, more aggressive maneuvers
including mechanical thrombectomy, aspiration thrombectomy, and angioplasty are required to
establish a flow channel and promote thrombolysis. In these cases, aggressive use of
nitroglycerin may be called for to treat spasm, which can be a confounding factor when
performing endovascular procedures in the upper extremities.
REVASCULARIZATION OF ACUTE TRAUMATIC INJURY

Injuries of the thoracic outlet vessels account for approximately 5% to 10% of acute vascular
trauma (135,136). The vast majority of acute injuries to the subclavian and axillary arteries are
secondary to penetrating trauma (137, 138, 139, 140) (Fig. 18-5), while 6% to 10% of the
injuries are due to blunt trauma (141). Iatrogenic injury, particularly from catheterization, is an
important etiology for brachial and more distal arterial injury (142).
With recent advances in endovascular techniques, particularly with the advent of low-profile
covered stents, percutaneous therapy has emerged as an important and viable therapeutic
option. Numerous case reports and small series of patients treated with endovascular therapy
have recently been reported with minimal complications and short-term patency rates
approaching 100% (135,137,143, 144, 145, 146, 147, 148, 149, 150, 151). Many of these
patients, however, are younger adults or even children and long-term patency rates, which have
not been sufficiently reported to date, remain a concern.
The spectrum of injuries to the innominate, subclavian, and axillary arteries includes vessel
transection, intimal disruption with or without thrombus formation, and false aneurysm or
arteriovenous fistula development. Pseudoaneurysms have been treated with placement of a
bare stent and subsequent coil embolization of the aneurysm sac (152). However, treatment
with covered stents with or without branch vessel embolization must be considered the
preferred technique. Arteriovenous fistulas, including those of the subclavian and proximal
carotid arteries, have also been treated successfully with covered stents (135,137,151).
Vascular transection and injuries with severe intimal disruption have been treated
percutaneously but carry increased risk of causing active arterial extravasation or distal embolic
disease.
While open surgical treatment has resulted in excellent short- and long-term patency rates, it
carries reported morbidity and mortality rates of 5% to 30% (153). There are numerous other
disadvantages to surgery including difficult exposure in a contaminated area with many
important neurovascular structures in patients with potential ongoing hemorrhage and distorted
anatomy. In addition, these patients may have multiple acute comorbidities and are often poor
candidates for general anesthesia. Endovascular techniques offer the advantage of working
under conscious sedation from a remote site with decreased blood loss and shorter procedure
times.
The majority of these patients present to the emergency department with an immediate history
of penetrating or blunt trauma. Most patients with acute subclavian occlusions will have viable
limbs due to the rich supply of collateral vessels. However, those with axillary and brachial
injuries may have a threatened extremity, with a critical ischemia time of as little as 4 hours
after the injury (141). Alternatively, subtotal occlusions may present with a painful but
nonthreatened extremity. While the level of an extremity injury can be evaluated with physical
examination and ultrasound, detection of central vascular lesions requires a high index of
suspicion and can be evaluated with CTA in stable patients or immediate angiography or
surgery in unstable patients (Fig. 18-2). Based on the data obtained by Schwartz and Weaver
in 1993, we perform emergent angiography for extremities with pulse deficits and wrist-brachial
indexes of <1.0 to 0.9154.
Initial arch aortography is usually performed with a pigtail catheter in LAO and AP projections
from a common femoral
artery access. This is followed by catheterization of the affected extremity and an upper
extremity runoff examination focused on the level of injury. Pseudoaneurysms and AV fistulas
can be treated with covered stents after the lesion is crossed with a glide wire and catheter.
Cannulation of the subclavian artery with a long sheath facilitates delivery of the stent and
allows for contrast injections during and after stent placement. Vessels that are occluded from
transection or those with severe intimal disruption may require surgery. These lesions can
sometimes be crossed and treated with covered stents, but a surgical team should be
immediately available, as guide-wire traversal can precipitate active extravasation. For these
cases and those with ongoing extravasation, a standard occlusion balloon catheter (Boston
Scientific Corp.) should be available to stop the bleeding while the patient is transferred to the
operating room. Even for those cases without ongoing extravasation that require surgical
therapy, a balloon occlusion catheter may help the surgeon localize the lesion and provide initial
proximal control of bleeding in the operating room.
FIGURE 18-5. An 18-year-old status post-gunshot wound. A: AP arch aortogram

demonstrates traumatic injury (arrow) to the subclavian artery adjacent to the origin of the
thyrocervical trunk. Note right aortic arch. B: Completion angiogram shows exclusion of
pseudoaneurysm with Wallgraft endoprosthesis (Boston Scientific Corp., Maple Grove,
MN).
We have treated most of our acute and subacute proximal traumatic lesions with the Wallgraft
Endoprosthesis (Boston Scientific Corp.), a Wallstent covered with Dacron graft material (Fig.
18-5). Newer covered stents including the Fluency (Bard Inc., Tempe, AZ) and Viabahn (Gore
Inc., Flagstaff, AZ) offer further options and the potential advantages of PTFE as the graft
material in addition to a more flexible Nitinol stent skeleton. The highest likelihood of stent
fracture involving the subclavian artery occurs at the junction of the clavicle and first rib (119),
and stents should not be placed in this location if it can be avoided. If branch vessels arise from
a false aneurysm, embolization of the branches should be performed before stent placement to
avoid endoleak. In addition, the stent should be oversized 10% to 15% to ensure a good seal.
Recovered patients can be followed with serial upper extremity blood pressure measurements
and CTA. While short-term results of covered stent placement for trauma are excellent, long-
term patency results are unknown and in-stent restenosis is a concern. Consequently, each
patient's care should be tailored individually based on age, comorbidities, and other factors.
OTHER CAUSES OF PROXIMAL UPPER EXTREMITY

ARTERIAL DISEASE
Less than 5% of cases of thoracic outlet syndrome are vascular in origin, and only a small
percentage of these are arterial (155). While duplex ultrasound and MRA are useful imaging
tools that can be performed with and without a provocation maneuver (e. g., hyperabduction,
costoclavicular or Adson maneuvers), angiography remains the gold standard. The value of
finding a positive response to provocation is limited since this can be elicited in normal
asymptomatic subjects. Arteriographic findings in true arterial cases of thoracic outlet syndrome
include narrowing, obstruction, poststenotic dilatation, and aneurysmal disease with or without
mural thrombus involving the subclavian artery at the thoracic outlet, as a result of repetitive
trauma from external compression. Since the cause of thoracic outlet syndrome is extrinsic to
the artery, treatment consists primarily of surgical decompression to relieve the cause of
obstruction and possible vascular repair (6). In rare instances, thrombolysis may be performed
prior to surgery in patients who present with acute upper extremity ischemia, or patients may
present after surgery with recurrent disease at the site of repair that can be treated
endovascularly.
In younger patients without atherosclerotic disease or thoracic occlusion syndrome, other
causes of upper extremity ischemia should be considered. While cases of subclavian artery
fibromuscular dysplasia have been reported (156), Takayasu arteritis should be the leading
consideration in women under the age of 40. Patients in the acute phase of this autoimmune
disorder present with marked constitutional symptoms, pain over the affected vessels, and an
elevated erythrocyte sedimentation rate (ESR). Symptoms often improve with administration of
steroids, and revascularization should not be attempted during this acute phase. The burned-
out or pulseless phase often involves all three supra-aortic trunk vessels and definitive
diagnosis is made with arteriography, which demonstrates occlusions or long areas of smooth
stenosis between areas of normal vessels. Surgical bypass may ultimately be required.
Embolic disease is only occasionally a factor when the chronic form of the disease is
complicated by aneurysm formation (50,111).
FIGURE 18-6. A, B: Patient with bilateral arm claudication due to giant cell arteritis has
bilateral long smooth narrowing (arrows) of distal axillary and proximal brachial arteries.
Giant cell arteritis is another autoimmune disorder that has a similar angiographic appearance
involving the supra-aortic trunk vessels (Fig. 18-6). This process usually occurs in women older
than 60 and some have suggested that these entities represent the same disease process with
a bimodal peak (51). Although these patients usually present with the classic symptom complex
of temporal arteritis, polymyalgia rheumatica, and elevated ESR, upper extremity claudication
has been reported in numerous patients. Revascularization is contraindicated since symptoms
resolve with the administration of steroids (157).
Buerger's disease (thromboangiitis obliterans) usually affects the distal upper extremity arteries
in young smokers but can occasionally affect the more central large and medium-sized arteries
(158).
Radiation therapy for breast carcinoma, or less commonly Hodgkin's lymphoma, is another
recognized cause of proximal upper extremity occlusive disease (159, 160, 161, 162, 163). The
process occurs 2 to 42 years after radiation therapy and is similar to atherosclerotic disease
with the exception that smaller arteries in the field are affected as well (161), thus leading to a
paucity of collaterals and exaggerated symptoms when occlusive disease occurs. Recent
authors have suggested that this entity be treated in similar fashion to traditional atherosclerotic
disease including appropriate modification of risk factors and revascularization when indicated
(164,165). Endovascular techniques are particularly appealing in this group of patients because
the irradiated field complicates surgical therapy and increases the risk of infection as well as
other adverse events (165).
CONCLUSION
Occlusive arterial disease of the upper extremities represents a complex spectrum of pathology
that is distinct from but less common than that of the lower extremities. Atherosclerosis remains
the most common cause of chronic disease, while embolic disease and trauma account for the
majority of acute cases of upper extremity ischemia. Although surgical therapy remains the gold
standard due to good long-term patency rates, the emergence and ongoing refinement of
endovascular techniques provide patients with less invasive options for upper extremity
revascularization, which have lower complication rates than surgery and excellent short-term
patency rates. While further studies are needed to evaluate its long-term patency, endovascular
therapy plays a major role in the management of upper extremity ischemia and may be
considered the treatment of choice for chronic proximal upper extremity occlusive disease.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 19 - Lower Extremity Arterial
Revascularization
Chapter 19
Lower Extremity Arterial Revascularization
James L. Swischuk
Bob H. Smouse
Chris Vargo
Peripheral arterial disease (PAD) of the lower extremity in its broadest sense includes occlusive
disease, aneurysmal disease, vasculitis, thromboembolic disease, venous disease, and
lymphatic disease. For the purposes of this chapter the term PAD is used to encompass the
most common causes of occlusive disease, atherosclerosis and thromboembolic disorders.
These processes, which lead to either gradual or abrupt occlusion of the vasculature, are a
significant cause of end-organ dysfunction and failure.
The prevalence and incidence of PAD in the general population increase with age, and it is
uncommon for men <35 years of age and women <45 years of age to be symptomatic. The
incidence of claudication in individuals between 30 and 44 years of age is 6 in 10,000 and 3 in
10,000 for men and women, respectively. However, for individuals between 65 and 74 years of
age, the incidence of claudication rises 10-fold, to 61 in 10,000 and 54 in 10,000 for men and
women, respectively (1). Furthermore, when high-risk groups including smokers, diabetics over
the age of 50, and any individual over the age of 70 were screened for PAD, 29% of this cohort
was found to have PAD with 16% also possessing other forms of atherosclerotic disease (2).
The single most common cause of PAD is atherosclerosis. Atherosclerosis has many well-
established risk factors, which include smoking, diabetes, hypertension, hyperlipidemia, family
history of PAD, age, male gender, hyperhomocysteinemia, and others. Some of these entities
are ubiquitous and powerful risk factors, and will be mentioned separately to further appreciate
the role they play in the PAD patient.
Other than atherosclerosis, there are a number of other conditions that can cause gradual or
abrupt occlusion of the lower extremities. Thromboembolic disease can contribute to acute
occlusions that will require more urgent attention. The popliteal artery is a common location for
occlusive disease from etiologies other than atherosclerosis. These include aneurysmal
disease, entrapment conditions, and cystic adventitial diseases. The latter two conditions
should be considered especially when the patient with popliteal artery occlusion is relatively
young (under the age of 50) and has no significant risk factors for atherosclerosis. In addition,
vasculitis, trauma, and congenital abnormalities may lead to significant lower extremity arterial
occlusions.
RISK FACTORS
Cigarette Smoking
Cigarette smoking is clearly one of the most significant risk factors that lead to PAD, and
certainly the most common preventable cause of atherosclerosis (3). Although the effects of
cigarette smoking can affect any vessel in the body, the effects that smoking has on the large
vessels of the body (>4 mm) can be especially devastating. Considering this, it is no surprise
that smokers are two to three times more likely to suffer from lower extremity PAD than
coronary artery disease (4). Furthermore, of patients with lower extremity PAD, 80% will have
a medical history significant for smoking (5,6). Anecdotally, when diagnostic arteriography
reveals severely atherosclerotic proximal vessels of the lower extremity containing heavy
calcification, deep ulcerations, and severe stenosis, it is almost certain that the patient has a
very long and significant history of cigarette smoking.
Diabetes Mellitus
Diabetes mellitus is another extremely potent contributor to PAD of the lower extremities (5, 6,
7). It differs from smoking in that it tends to have the greatest impact on the smaller vessels
(<5 mm) of the body, and therefore in the lower extremity this risk factor contributes
significantly to occlusive disease from the popliteal artery distally. As a result, the diabetic
patient with lower extremity PAD will tend to suffer from the effects of small vessel disease
(i.e., critical limb ischemia [CLI]), rather than the effects of more proximal disease
(claudication). In fact, while the patient with diabetes can expect a 3.5- to 8.6-fold increase risk
of developing claudication (8), there is a 7- to 15-fold increased risk of undergoing major
amputation secondary to CLI (9, 10, 11).
Hyperlipidemia
Hyperlipidemia is an etiologic factor that affects the entire vascular bed including the lower
extremities. More specifically, one can expect increase levels of total and low-density
lipoprotein cholesterol and decreased levels of high-density lipoprotein in patients with
symptomatic lower extremity PAD (7,12,13). There is a linear relationship between increasing
levels of cholesterol and the occurrence of lower extremity PAD (14, 15, 16). Although the
association of hypertriglyceridemia with PAD is less clear (17, 18, 19, 20, 21), the consensus
view supports the positive association between elevated triglycerides and lower extremity PAD
(3,12,13).
Hypertension
Hypertension is one of the most common findings in the PAD patient; however, hypertension, in
general, is a common finding in the elderly. This is because with age there is decreased
compliance and distensibility (or increased stiffness) of the central arteries (22), which lead to
increased systolic blood pressure and pulse pressure (23). Whereas smoking and diabetes
clearly cause most, if not the majority, of cases of atherosclerosis
seen clinically, the causal relationship between hypertension and PAD is less clear. Some
studies show that hypertension increases the risk of developing PAD, while others do not
(5,12,16,24).
TABLE 19-1 CLASSIFICATION OF PERIPHERAL ARTERIAL DISEASE:

FONTAINE'S STAGES AND RUTHERFORD'S CATEGORIES
Rutherford
Stage Fontaine clinical Grade Category Clinical
I Asymptomatic 0 0 Asymptomatic
IIa Mild claudication I 1 Mild claudication
IIb I 2 Moderate claudication

Moderate to severe claudication
I 3 Severe claudication
III Ischemic rest pain II 4 Ischemic rest pain
IV Ulceration or gangrene III 5 Minor tissue loss,
IV 6 Ulceration, or gangrene
Reprinted from Dormandy JA, Rutherford RB, for the TransAtlantic Inter-Society
Consensus (TASC) Working Group. Management of peripheral arterial disease (PAD).
J Vasc Surg. 31:S1-S296, 2000, with permission from Elsevier.
The truth is likely that in some instances hypertension leads to atherosclerosis and in others
atherosclerosis leads to hypertension as follows. As mentioned above the increased stiffness of
the central arteries that occurs with age contributes to hypertension (23); therefore, it is likely
that diffuse atherosclerosis will further contribute to the loss of arterial compliance, which may
serve to exacerbate preexisting hypertension. Another instance where PAD contributes to
hypertension is renovascular hypertension, in which PAD of the renal arteries is the cause of or
contributes to hypertension in some patients (25,26). Clinically it is uncommon to encounter
patients who have significant PAD with hypertension as their sole risk factor. Nonetheless,
considering the well-known consequences of hypertension on end organs such as the heart,
brain, and kidney, hypertension is a risk factor that warrants close monitoring and aggressive
treatment.
AGE AND GENDER
With increasing age there is an increasing prevalence of lower extremity PAD. For men under
the age of 50 the prevalence of claudication is 1% to 2%, while for men over the age of 70 the
prevalence of PAD increases to 5% (27,28). Men experience the symptoms of lower extremity
PAD earlier than women. This is especially the case for patients under the age of 70. Over the
age of 70, the protective effects of estrogen are diminished, and the prevalence of PAD for
men and women become nearly identical (28).
CLINICAL PRESENTATIONS
PAD of the lower extremities produces a variety of clinical presentations that range in severity
from lifestyle limiting to limb and life threatening. For the vast majority of patients who present
with symptomatic PAD of the lower extremity, symptoms will fall into one or more of the
following three clinical presentations. These include the chronic symptoms of claudication and
CLI and the more acute symptoms of thromboembolic disease. In addition, many patients will
present with a combination of both chronic (claudication, CLI) and acute symptoms as the result
of antecedent chronic disease leading to thrombosis of the limb.
Traditionally the vascular bed of the lower extremities has been divided into three anatomical
segments. These include the aortoiliac, femoropopliteal, and tibial vessel segments. When
atherosclerotic disease occurs in each segment there are tendencies to produce slight
variations in clinical presentations. For instance, proximal disease (aorto-iliac and
femoropopliteal segments) will be primarily responsible for symptoms of claudication, while
distal disease (below the knee) is unlikely to cause claudication and most often presents with
symptoms of CLI. Furthermore, there are many patients with multisegment complex disease.
These patients can present with almost any combination of symptoms that include claudication,
CLI, and acute ischemia. Chronic and acute forms of lower extremity PAD have been
categorized previously using the Fontaine and Rutherford classifications systems (Table 19-1).
These classification systems were developed primarily to standardize the reporting of clinical
studies that evaluate the surgical, endovascular, and medical treatments of PAD (29,30).
There is also a fourth segment, the microcirculation. Given that disease in the very distal
vascular bed is not amenable to conventional imaging and few treatments are directed at this
segment, the microcirculation is often given little attention in traditional teaching and clinical
practice. Nonetheless, disease in this segment alone can be significant and solely responsible
for limb loss. This is never more apparent than in the diabetic patient with gangrene of the distal
foot despite the presence of palpable pedal pulses.
Claudication
Claudication, in the classic sense, is pain in the lower extremity, which occurs at a predictable
walking distance, which then subsides within 5 to 10 minutes after rest. The character of the leg
discomfort can be variable, with patients describing the pain as cramping, a deep muscle ache,
burning, or simply premature leg fatigue. Although the character of the discomfort is variable
from patient to patient, the character of the pain or fatigue for any given individual will be
consistent. In addition, the discomfort is centered in the muscle groups of the leg, as the cause
of discomfort is insufficient blood flow to keep up with the increased metabolic demands of the
muscle groups used during exercise.
From a clinical standpoint, the most consistent findings among all patients with claudication are
the exclusive occurrence of symptoms with exercise, the fairly rapid relief with rest (5-10
minutes), and the predictability of symptoms; that is, symptoms occur almost every time the
patient walks at a
normal pace. The latter finding is in fact what makes claudication lifestyle limiting. The patient
chooses not to perform activities of daily living to avoid the predictable symptoms of
claudication. As a result, interventions are performed on patients with claudication for no other
reason than enhancing their quality of life. Interventions are not performed on patients with
claudication to preserve the limb, given that few patients with claudication will progress to CLI
during their lifetime (31,32).
As stated previously, the anatomic level that occlusive disease occurs in the patient with
claudication is in the more proximal aorto-iliac and femoropopliteal segments. This is because
the vessels of the leg are simply conduits that supply blood to more distal segments. More
precisely, the level of obstruction is almost always proximal to the symptomatic muscle groups.
For example, femoropopliteal disease will have symptoms limited to the calf and, on rare
occasion, the foot, while aorto-iliac disease can cause calf, thigh, and buttock claudication.
Furthermore, buttock claudication will almost always predict disease in the aorta or common
iliac arteries, one caveat being the patient with hypogastric artery disease.
As mentioned previously, claudication is a lifestyle-limiting disease with only a marginal risk to
the limb; therefore, goals of treatment are to improve the quality of life while subjecting the
patient to a limited degree of risk. The successful treatment of claudication can include
exercise, pharmacotherapy, and revascularization (both surgical and endovascular). Numerous
studies have confirmed the benefits of a supervised walking program with and without cilostazol
(Pletal; Otsuka America Pharmaceutical, San Francisco, CA) for significantly improving pain-
free walking distance and quality of life (33, 34, 35, 36), however, the durability of the clinical
benefit gained is contingent on the continued adherence to the prescribed exercise program
(37).
In contrast to the medical management of claudication, revascularization procedures, whether
surgical or endovascular, require the patient to assume increasing amounts of risk. For the
most part, the risks of endovascular procedures are low, and therefore, this approach in the
appropriate anatomical setting is an accepted treatment option for the patient who has failed or
is unlikely to benefit from medical management. For those patients choosing surgical
revascularization, there must be careful consideration of the increased risk of surgery when
treating this relatively benign condition. Whatever the method of revascularization for the patient
with claudication, the treatment should be designed to provide a durable benefit while subjecting
the patient to limited risk.
For the patient with classic symptoms of claudication, the diagnosis can be made clinically with
some degree of confidence. However, some patients may have less than classic symptoms, or
more often, they may have other nonrelated symptoms in the lower extremity that cloud the
clinical picture. In any event, most patients will undergo a noninvasive duplex evaluation of the
lower extremities. For patients with claudication, the noninvasive evaluation should include
postexercise studies (38). Fairly limited disease can cause significant symptoms in some
patients, and the physiologic effects of limited disease may become apparent only after the
limb is stressed (39). Once the physiologic findings of the noninvasive duplex exam confirm the
diagnosis and the decision is made to pursue revascularization, the patient may proceed to
more anatomical imaging studies such as computed tomography angiography, magnetic
resonance angiography, and conventional angiography.
Critical Limb Ischemia

CLI is any condition where there is an overwhelming likelihood that the limb is at risk for
amputation or significant tissue loss within 6 months. However, for most patients presenting
with CLI the risk of limb loss is fairly immediate, and the need for revascularization is more
urgent than for the patient with claudication.
These conditions include rest pain, gangrene, nonhealing ulcers, and cellulitis that is refractory
to antibiotic therapy in the presence of significant arterial occlusive disease. In these instances
the degree of occlusive disease is more severe than typically seen with claudication, and is
most often multisegmental, with ankle-brachial indexes <0.5. For most patients successful
treatment hinges on complete revascularization of the limb through the tibial vessel segment,
which can be especially challenging given the diffuse nature of the disease seen in these
patients.
In most instances of CLI, the risk-benefit ratio is different from that seen with the claudicant;
with limb loss looming, there is greater latitude in performing endovascular and surgical
procedures of greater complexity (and greater risk) and greater acceptance in performing
procedures of more limited durability. Endovascular procedures will at times include long
segment recanalizations and treatment of smaller-caliber tibial vessels. Surgery may include
femorodistal bypasses using venous conduit. Whenever possible, the goal should be to
establish straight-line flow to the foot. The risks of these more complex procedures are
outweighed by the impending risk of amputation. Procedures will be performed in this setting
that have limited durability as long as it is felt that the procedure will have a reasonable chance
of providing blood flow during the period of healing. Once the limb is healed, the metabolic
demand of the limb will decrease, and restenosis or reocclusion of the treated segment may be
of limited clinical significance.
A caveat to the above is the patient with rest pain. Rest pain is a specific entity in which there is
insufficient blood flow to support the limb at rest. The pain occurs in the foot when the patient is
in the recumbent position, typically at night when the patient goes to bed. The pain involves the
foot simply because the foot is the part of the limb that is farthest from the heart and will
therefore experience the greatest degree of ischemia. Furthermore, when asked what relieves
the pain, the patient will typically report that the pain is relieved by hanging the foot over the
side of the bed or with ambulation. In both instances relief of symptoms occurs when the foot is
placed in the dependent position, which increases the hydrostatic pressure of the blood column
in the lower extremity, i.e., the perfusion pressure in the foot. The goals in treating rest pain are
slightly different from those of treating other forms of CLI. Any improvement in blood flow will
typically bring some relief, so straight-line flow to the foot is not the imperative. In addition,
durability of treatment is of more significance in this instance than with other forms of CLI, as
recurrent disease will often bring recurrent symptoms.
Thromboembolic Disease
Thromboembolic disease or acute limb ischemia occurs when there is an abrupt change in the
clinical condition of the lower extremity due to an acute deterioration in blood flow. Most often,
this is the result of thrombosis of an arterial segment with preexistent PAD, emboli from a
proximal source, and thrombosis of peripheral artery aneurysms, that is, popliteal artery
aneurysms. Regardless of the cause, the need for revascularization in many of these patients is
either urgent or emergent. The classic presentation of acute limb ischemia includes the five
Ps: pain, paralysis, paresthesias, pulselessness, and pallor. In addition, for those patients
with a history of lower extremity bypass or recent revascularization of any type, any complaint
of an abrupt change in the condition of the limb, even if symptoms are not classic, should raise
the question of acute thrombosis.
TABLE 19-2 CLINICAL CATEGORIES OF ACUTE LIMB ISCHEMIA
Finding Doppler signals
Muscle
Category Description/prognosis Sensory loss Arterial Venous
weakness
Not immediately
I. Viable None None Audible Audible
threatened
II. Threatened
Minimal
a. Salvageable if
(toes) or None Inaudible Audible
Marginally promptly treated
none
More than
Salvageable toes;
b. Mild,
with immediate associated Inaudible Audible
Immediately moderate
revascularization with rest
pain
Major tissue
loss or Profound,
Profound,
III. Irreversible permanent paralysis Inaudible Inaudible
anesthetic
nerve damage (rigor)
inevitable
Source: Reprinted from Rutherford RB, Baker JD, Ernst C, et al. Recommended standards
for reports dealing with lower extremity ischemia: revised version. J Vasc Surg. 26:517-538
1997, with permission from Elsevier.
For some, albeit few, the degree of ischemia is so severe that revascularization needs to be
performed within hours. For others, acute thrombosis will lead to the sudden onset of nonlimb-
threatening conditions such as claudication. For the latter group revascularization can be
performed on a near-elective basis. Accordingly, any patient presenting with claudication must
be questioned with regard to the onset of symptoms, as this will differentiate claudication
secondary to chronic versus acute disease. Those with chronic disease will experience the
gradual onset of symptoms, while those with acute disease will report either the abrupt onset
or the exacerbation of symptoms. For the latter group, the patients will typically posses a
combination of acute thrombosis on chronic disease. The importance of determining the
presence of acute disease is that it will likely alter the therapeutic approach to the patient, and
all must be prepared for the possibility of thrombolytic therapy.
Patients with embolic disease often present with very severe ischemic changes, complaining of
the acute onset of very profound motor and sensory deficits. This is especially so when the
emboli are large, such as seen from a cardiac source, and the patient does not have
preexisting PAD. This scenario will create proximal occlusions in individuals who lack
established collateral pathways that would otherwise moderate symptoms. This is in contrast to
the patient who has thrombosis of a previously diseased segment. In this instance, the patient
may only complain of an acute exacerbation of chronic symptoms.
Blue Toe Syndrome

Blue toe syndrome is a unique form of embolic disease in which a proximal source causes distal
micro-embolization. Typical sources include very focal stenoses, ulcerated plaque, or
aneurysmal disease. Micro-emboli propagate distally and can severely compromise the
microcirculation, including the digital arteries of the toes. When this occurs, there are most
often multiple toes or small cutaneous patches demonstrating focal ischemia. The clinical
presentation can at times be impressive with severely ischemic and painful toes in the
paradoxical presence of palpable pedal pulses. The reason is that blue toe syndrome is the
result of micro-emboli from a proximal source traveling through a patent vascular tree to a distal
target, the foot. The patient can often be reassured that despite impressive ischemic changes,
the proximal offending lesions are typically amenable to endovascular therapies (40,41). In
addition if the affected limb demonstrates any occlusions at arteriography, then acute
thrombosis of this segment should be suspected, and thrombolysis should be considered.
The Rutherford criteria (Table 19-2) categorize acute limb ischemia according to multiple clinical
and noninvasive findings (29). These criteria are used to designate the limb as viable,
threatened, or nonviable. In general, limbs that are considered viable and marginally threatened
(categories I and IIa) are candidates for more traditional forms of catheter-directed
thrombolysis, while immediately threatened and nonviable limbs (categories IIb and III) require
more rapid restoration of blood flow that will mandate either surgery or aggressive
pharmacomechanical thrombolysis.
Although noninvasive imaging studies can quantify the degree of vascular compromise, the
decision as to whether the patient will require immediate revascularization is most often made
at the bedside. The two most important clinical findings when examining the patient are the
degrees of paralysis and paresthesias. A great deal can be learned about the degree of
ischemia by asking the patient to move the toes and feet and by determining the level of
sensory loss. A patient with numbness over the entire foot and little or no motor function in the
toes and feet will require revascularization within hours, while the patient with numbness limited
to the toes and sluggish toe movement will likely do best with catheter-directed thrombolytic
therapy, which, in fact, may take several hours to improve blood flow. For those patients with
preexisting sensory or motor function deficits (as seen with a previous stroke or with preexisting
neuropathy), the clinical exam is compromised and decisions concerning the course of
treatment will favor a more aggressive approach. The decision to perform surgery versus
endovascular therapy will be influenced by the level of surgical risk and operator comfort with
newer mechanical thrombolytic devices.
ENDOVASCULAR TREATMENTS
Aorto-iliac Segment
Symptoms
The classic presentation of aorto-iliac segment vascular disease is claudication. As mentioned
previously, claudication symptoms are often referable to the next lower muscle group; for
example, isolated aortic stenoses will often present with bilateral buttock claudication while
disease involving more
caudal arteries, such as the external iliac artery, presents with thigh claudication. However, it is
important to remember that aorto-iliac disease can and does cause symptoms throughout the
entire lower extremity.
Surgical versus Endovascular Treatments

Individuals with intermittent claudication should be counseled on noninvasive therapies and show
significant disability before proceeding with treatment. Several studies have shown benefit of
exercise in patients with disabling claudication. Lundgren et al. compared bypass, exercise, and
a combination of the two and demonstrated that the combination of exercise and surgery
yielded a larger improvement in walking distance than either surgery or exercise alone: the
increases in absolute claudication distances were 263%, 173%, and 151%, respectively (42).
Creasy et al. compared exercise alone to percutaneous transluminal angioplasty (PTA) alone
and found greater short-term improvement with exercise alone compared to PTA. The
increases in absolute claudication distances were 442% and 57%, respectively (although this
improvement gap disappeared over time) (43). The American Heart Association Practice
Guidelines list the following recommendations: individuals who are offered the option of
endovascular or surgical therapies should (a) be provided information regarding supervised
claudication exercise therapy and pharmacotherapy; (b) receive comprehensive risk factor
modification and antiplatelet therapy; (c) have a significant disability, either being unable to
perform normal work or having serious impairment of other activities important to the patient;
and (d) have lower extremity PAD lesion anatomy such that a revascularization procedure
would be low-risk and have a high probability of initial and long-term success (44).
Aorto-iliac segment disease represents one of the best indications for PTA with or without
stenting. Endovascular treatment in these large, high-flow vessels yields excellent long-term
patency rates. In an exhaustive meta-analysis of multiple published PAD studies by Kandarpa et
al. (45), iliac balloon angioplasty demonstrated a primary patency rate of up to 86%, (range:
60%-86%) at 1 year, declining to 74%, (range: 44%-74%) at 4 years. With the addition of
selective stenting, primary patency rates improved to 91%, (range: 69%-91%) at 1 year,
declining to 78%, (range: 53%-78%) at 4 years (45). The results of iliac PTA and stenting
compare favorably to those of surgical bypass. Additionally, access to the aorto-iliac segment
is usually straightforward. The best results are for focal stenoses in the common iliac artery
with maintained runoff into a patent superficial femoral artery (SFA) (46). Indicators for risk of
failed primary patency include long segment stenoses or occlusions, occluded SFA runoff (47),
concurrent ipsilateral external iliac disease, complication during treatment, need for
thrombolysis (48), small iliac artery diameter (49), and young age (50). Surgical bypass
remains the gold standard but carries higher morbidity and mortality risks. The advantage of
surgical bypass is longer primary patency in most cases.
Angioplasty versus Stenting

The ideal lesion for iliac PTA is a short (<2-cm), focal, concentric stenosis in the aorta or
common iliac artery. At the other end of the spectrum are patients with bilateral long-segment
occlusions of the common and external iliac arteries. These patients should be considered for
more complex percutaneous interventions or perhaps for surgical bypass. Iliac stenting
(compared to PTA alone) is effective for longer-segment disease, eccentric lesions, and
recanalizations. It is also used to assist with failed or suboptimal PTA results (46). At our
institution we consider suboptimal PTA results to include elastic recoil, flow limiting dissection,
residual stenoses >30%, or a residual mean pressure gradient >5 mm Hg, or a >10 mm Hg
systolic pressure gradient. We use balloon-expandable stents for origin stenoses or occlusions
and use self-expandable stents for nonostial lesions and for tortuous vessels, such as the
external iliac artery, in most cases.
Infra-inguinal (Femoropopliteal) Artery Disease

Symptoms
Stenoses and occlusions are more common in this arterial segment than in any other vascular
bed. Lesions are typically long, multiple, and ulcerated. Dense calcification is common. Given
the location of the disease the symptoms of classic intermittent claudication typically are limited
to the calf with cramping and leg tiredness following walking and stair climbing. The disease
process is usually slow, progressive, and disabling. Claudication can be bilateral, though often it
is worse in one leg. However, those with unilateral claudication are often found to have bilateral
disease with noninvasive imaging (44).
Surgical versus Endovascular Treatment

Intervention by endovascular or surgical procedures should be reserved for those patients who
have failed or are unlikely to benefit from exercise and medical therapies. Once medical
therapies have been exhausted, treatment with endovascular therapy should be considered the
first choice in most patients. Used judiciously, endovascular therapies such as PTA, stenting,
and other means of revascularization will allow future treatments including repeat angioplasty,
stenting, and surgical bypass if needed. Surgical bypass as a first-line invasive therapy for
intermittent claudication may compromise future target vessels. Most failed surgical grafts
present with acute thrombosis and require thrombolysis at a minimum and surgical revision in
some cases. Thrombosis of a surgical bypass graft may present with acute limb-threatening
ischemia and result in amputation, whereas failed endovascular therapies usually present with
neointimal hyperplasia or progression of adjacent disease and can be treated with repeat
angioplasty or stenting, usually on an outpatient basis. Surgical bypass is still considered the
gold standard and has the advantage of greater durability in some cases.
Unfortunately, durable therapies for the SFA and popliteal arteries have been elusive for both
surgical and endovascular forms of treatment. The femoropopliteal segment is a long artery
usually diffusely diseased, which undergoes strenuous conformational changes with ambulation.
Perhaps due in part to this, traditional treatment choices have lacked consistency in durability.
The optimal choice of therapy is often confusing and long-term patency elusive. Furthermore,
debate arises as to which patients and disease states fare best with endovascular therapy and
which fare best with surgical interventions.
Primary patency rates for simple PTA vary widely from report to report. The aforementioned
meta-analysis demonstrated 1-year patency rates for PTA to vary from 26% to 79%, declining
to 12% to 68% at 5 years (45). Treatment of focal stenoses had higher patency rates and long-
segment stenoses and occlusions had lower patency rates. With the advent of selective
stenting, primary patency rates have improved slightly but still lack consistent outcomes.
Primary patency rates for stenting in this segment were found to vary from 48% to 80% at 1
year, declining to 22% to 86% at 3 years (45). Comparing PTA to surgery, PTA of focal
stenoses has a risk of long-term failure equivalent to that of synthetic bypass grafts
(polytetrafluoroethylene) and twice that of venous bypass grafts (51).
For recommendations on treatment of the SFA and popliteal arteries one can refer to the
TransAtlantic Intersociety
Consensus (TASC) document. The objective of TASC is to promote uniformity in the
management and treatment of patients with PAD worldwide. The TASC recommendations for
endovascular and surgical revascularization of the femoropopliteal arterial segment are based
on lesion morphology and disease extent. Lesions can be divided into four morphologic groups,
A, B, C, and D. Type A is defined as a single stenosis <3 cm long. Type B is defined as a single
stenosis 3 to 10 cm long not involving the popliteal artery or multiple stenoses, each <3 cm.
Type C is defined as a single stenosis or occlusion longer than 5 cm or multiple stenoses or
occlusions, each 3 to 5 cm, with or without heavy calcification. And TASC type D is defined as
complete common femoral artery or superficial artery occlusions or complete popliteal and
proximal trifurcation occlusions. Endovascular procedures are the treatment of choice for type A
lesions, as is surgery for type D lesions. Treatment of TASC B and C lesions is still under
debate. However, with the newer Nitinol stents used in the femoral and popliteal arteries,
encouraging data are emerging for endovascular treatment for most type B lesions and some
type C lesions (30).
Biomechanical Forces in the Femoropopliteal Segment

Physicians have reported stent fractures in self-expanding Nitinol stents placed in the SFA and
popliteal arteries (52,53). The impact of stent and strut fractures on patient well-being is still
under investigation, with concerns that fractured stents will result in thrombosis, early stenosis,
and pseudoaneurysm formation. The importance of stent strut fractures has surfaced as a
result of the strong interest in using similar self-expanding drug-coated stents in the peripheral
vasculature.
Stent fractures may impact drug- and non-drug-eluting stent systems in three ways: (1) stent
fractures could disrupt uniform drug delivery, (2) fractured stents may cause vessel injury, and
(3) the mechanical stresses found in this arterial system may delay vessel healing and stent
incorporation, requiring prolonged drug delivery, an additional variable not found in the coronary
arterial system (54). The conformational changes that occur in the femoropopliteal arterial
segment are strong enough to pull apart or deform a hardened metal device (stent) causing
fractures and kinking (see Fig. 21-11 also).
A human cadaver study evaluating conformational changes in the femoropopliteal segment
demonstrated that axial compression and bending of the femoropopliteal arterial segment were
major changes that occurred with walking, sitting-to-standing, and stair-climbing movements.
Two different commercially available stents were used in the study to evaluate the effect of
stenting on the femoropopliteal arterial segment and also the effects that extremity movement
may have on the stent itself and the stented artery. One brand of stent was relatively flexible
and the other brand was relatively rigid (54). The flexible stent resulted in less distortion of the
bare and stented artery and resisted kinking behind the knee. The more rigid stent kinked
behind the knee with maximum bending and also caused exaggerated conformational changes
(excessive bending) in the adjacent unstented artery. These changes were consider significant
and may explain fractures and poor patency rates in certain stent designs.
With knee bending the unstented popliteal artery assumes a smooth contour (Fig. 19-1). When
a flexible stent is placed into the popliteal artery normal axial compression of the artery is
compromised and the stented artery begins to deform to allow overall foreshortening of the
segment (Fig. 19-2). When a more rigid stent is placed in the popliteal artery, stent flexibility is
limited and the stent is at risk for kinking (Fig. 19-3). Additionally, severe conformational
changes were also observed in the more rigid stent placed behind the knee with maximum knee
bending. These included out-of-plane stent shifting between two adjacent, nonoverlapping
stents and stent twisting, compression, and kinking (Figs. 19-4 and 19-5).
FIGURE 19-1. Smooth contour to unstented popliteal artery with knee bend.
Because of the risk of stent failure extra care must be taken when choosing a treatment plan
for this vascular segment. Using rigid stents or excessive stenting behind the knee may result in
fractures, kinking, and lower patency rates.
FIGURE 19-2. Deformed flexible stent behind knee with knee bending.
FIGURE 19-3. Kinked rigid stent behind knee with knee bending.
Infrapopliteal Disease
Of the major risk factors for PAD, diabetes is of particular concern with regard to the
development of infrapopliteal disease due to the predilection of atheromatous plaque to develop
within the tibial vessels in this patient population (30,55). In fact the incidence of diabetes in
patients who present for tibial artery angioplasty for limb salvage ranges from 63% to 91%
(30,55,56). Due to an excellent network of collaterals between the tibial and the peroneal
arteries, the patient with isolated focal areas of stenosis is unlikely to be symptomatic (57).
Rather these patients tend to present at a later stage with extensive multifocal (three-vessel)
disease and resultant CLI (57,58). Such patients require more urgent revascularization in the
form of surgical bypass or endovascular angioplasty/stenting or risk major limb amputation.
Unfortunately the surgical options of femorodistal and pedal bypass are technically demanding
and are associated with a 1.8% to 6% perioperative mortality (57,59, 60, 61).
Infrapopliteal Angioplasty
Angioplasty of the tibioperoneal trunk was reported as early as 1964 by Dotter and others;
however, these initial attempts achieved mixed results (62, 63, 64). Initially, complications
including vascular spasm, subsequent thrombosis, and lower extremity compromise limited
infrapopliteal angioplasty to situations of limb salvage in nonsurgical candidates (63,65). Over
the past several decades the introduction of new small-diameter balloons and guide wires and
the more liberal use of vasodilators and thrombolytics have significantly reduced these risks and
have made primary infrapopliteal angioplasty a viable alternative to surgical bypass (63,66,67).
FIGURE 19-4. Deformed, compressed, and twisted rigid stent with maximum knee
bending.
FIGURE 19-5. Out-of-plane shift of two nonoverlapping stents with knee bending.
Digital subtraction angiography (DSA) has traditionally been considered the gold standard for
assessing vessel anatomy in patients with vascular disease or injury (68,69). Studies have
shown that unless the technique of DSA is optimized, significant diagnostic errors can occur
during the evaluation of the infrapopliteal vessels (68,69). Depending on the severity of disease
an optimized examination should include selective external iliac artery or superficial femoral
arterial contrast injections (68). Such selective injections prevent dilution of contrast and help to
reduce patient motion, which allows for increased collimation and improved filter positioning
(68). Vasodilators or reactive hyperemia may also be employed to improve vessel opacification
(68). Lateral views of the calf and feet are also recommended in order to accurately display
anatomic structures (70). Optimized DSA has been shown to reliably demonstrate patency of
the infrapopliteal vessels with an overall sensitivity and specificity of 96% and 92%, respectively
(70). Both magnetic resonance angiography and computed tomography angiography have also
proven accurate in the depiction of peripheral vascular anatomy (69,71, 72, 73). In fact, the use
of lower extremity contrast-enhanced magnetic resonance angiography with dual-timing/dual
injection technique (separate acquisitions of pelvis and calves) has achieved an overall
sensitivity, specificity, and accuracy of 99%, 97%, and 98%, respectively (74,75).
Both contralateral and antegrade approaches can be used when performing infrapopliteal
interventions, although some have reported the contralateral retrograde femoral approach to be
less desirable (76,77, 78, 79, 80). The advantage of an ipsilateral antegrade femoral approach
is that it allows the greatest control by decreasing the overall distance to the tibial
vessels. Unfortunately, for many patients the antegrade approach is not feasible secondary to
large body habitus and a contralateral approach must be undertaken. This will require the use
of a contralateral sheath, which provides a few advantages. First, the contralateral sheath
provides the mechanical advantage needed when working in the very distal contralateral limb.
Also, the sheath provides access to the proximal vascular bed so that contrast and vasodilators
can be administered during interventions without performing cumbersome catheter exchanges.
Heparin should be administered (3,000-5,000 IU) to achieve an activated clotting time of 250 to
300 seconds (77,81, 82, 83). A floppy-tipped steerable guide wire (0.014 to 0.018 in.) is then
used to cross the stenotic lesion. Typically 3.0-Fr balloon catheters in the 2- to 4-mm range are
used in the tibial vessels. Nitroglycerin (100-g bolus) may be administered prophylactically or if
arterial spasm occurs during the procedure (82). During completion angiograms the presence
of residual stenosis should raise the suspicion of arterial vasospasm. This is especially so if the
area of residual narrowing is in the portion of the artery immediately adjacent to the area of
treatment. This can be further examined by performing subsequent angiograms after the
administration of nitroglycerin. Any improvement in the caliber of the vessel after the
administration of nitroglycerin indicates that the area of residual stenosis is due to vasospasm
and will clear with time.
The technical success rates for infrapopliteal angioplasty range between 78% and 100%
(77,83, 84, 85, 86, 87). Random effects meta-analysis demonstrates a technical success rate
of 93% and 1- and 2-year limb salvage rates of 79% and 74%, respectively (77,45). In
comparison, the limb salvage rates for distal bypass at 1 and 2 years are 79% and 74% (77);
however, up to one third of surgical patients require repeated interventions to maintain graft
patency (57). Given these results, current recommendations include the use of infrapopliteal
angioplasty for patients with CLI or in a patient with a failing distal bypass graft secondary to
stenotic outflow lesions (58). Regardless of the approach to the patient with infrapopliteal
disease, once treated the patient will require close clinical follow-up. Currently no published
data exist on the appropriate time intervals for follow-up of the patient who has undergone tibial
vessel interventions. However, the nature of the patient requiring such procedures mandates
close clinical and noninvasive follow-up.
Infrapopliteal Artery Stent Placement

Concerns about neointimal hyperplasia and thrombosis have limited the use of stents within the
tibial vessels (57,77). Stent placement within the infrapopliteal artery is generally not
recommended as a primary treatment option and is reserved for conditions of flow-limiting
dissection and elastic recoil (57,77). There have been published reports on the use of drug-
eluting stents within the tibial arteries; however, long-term patency rates have not yet been
established (91). In general, stenting of the tibial vessels requires borrowed technology
designed to treat the coronary circulation. The most significant limitation in using stents
designed for the coronary arteries is that the short stent lengths available (typically <2 cm) are
suboptimal for treating the longer segments of disease that are routinely encountered when
treating the infrapopliteal segment.
Thromboembolic Disease
As stated earlier, acute limb ischemia often requires urgent or emergent revascularization. Over
the last two decades catheter-directed thrombolysis has become the mainstay treatment for
acute lower limb ischemia, with surgery reserved for those limbs that present in the nonviable
condition. Landmark studies such as the Rochester, STILE, and TOPAS trials have collectively
demonstrated that the advantages of catheter-directed thrombolysis over surgery are improved
30-day amputation-free survival rates and the need for fewer subsequent surgical procedures
(89, 90, 91, 92).
TABLE 19-3 THROMBOLYTIC AGENTS AND TYPICAL ARTERIAL DOSING

(INFUSION)
Agent Dose
Alteplase; rt-PA (Genentech, Inc., South San Francisco,

0.25-1.0 mg/hour
CA)
Reteplase; r-PA (Centocor, Inc., Horsham, PA) 0.25-1.0 IU/hour
Tenecteplase; TNK-tPA (Genentech, Inc.) 0.25-0.5 mg/hour
60,000-120,000
Urokinase (Abbott Laboratories, Abbott Park, IL)
IU/hour
Currently, catheter-directed thrombolysis can be performed with a variety of lytic agents,

although no agent is U. S. Food and Drug Administration approved for catheter-directed
administration of drug in the arterial system. Even streptokinase, which has an indication for the
treatment of peripheral thrombosis, is only approved for intravenous administration. Table 19-3
lists currently available thrombolytic drugs and typical dosing when used in the peripheral
arterial system. Streptokinase has long since fallen from favor as a lytic agent due to the fact
that it is antigenic. This has led to the unpredictability of the drug concerning efficacy and
hemorrhagic complications (93, 94, 95). Urokinase has a long history as a safe agent for
catheter-directed infusions; however, the limited availability of urokinase (at present no longer
produced in the United States) and the substantial expense of the drug have led to markedly
diminished use of this agent. As a result, rt-PA has emerged as the most commonly used agent
in current practice.
All of the currently available lytic agents that are used in practice (urokinase, rt-PA, r-PA, and
TNK-t-PA) are effective. In fact, there are no reports showing the use of any of these agents at
any dose to be ineffective. Moreover, it can be said that when infusion rates decrease, the total
dose used decreases, and the length of infusion increases. When performing catheter-directed
arterial thrombolysis, amputation-free survival rates have been reported as 75% to 95%, and
thrombolytic success rates are usually slightly lower, ranging from 67% to 87%, regardless of
the agent used (91,92,96, 97, 98). Key to the success of any agent is the ability to place
infusion catheters directly into the offending thrombus, thereby creating high concentrations of
the drug in the clot while decreasing the likelihood of systemic hemorrhagic side effects.
The most significant complication seen with thrombolytic therapy is bleeding, with the most
severe form being intracranial hemorrhage. Major bleeding complication rates with peripheral
thrombolysis are typically >5% and have been reported at as high as 27% (91,92,96,99). The
most dreaded complication, intracranial hemorrhage, is much less common, seen in
approximately 1% of patients (90,99). During lytic therapy the risk of bleeding can be
moderated by using low-dose protocols, i.e., 0.25-0.5 mg rt-PA or TNK, and by using low-dose
heparin therapy during infusions (96). Empiric heparin dosing of 300 to 500 IU/hour has been
suggested as a safer alternative than full systemic heparinization (100). This is
especially so when protracted infusions are required. Theoretically another approach that may
help mitigate the risk of bleeding is to incorporate mechanical or pharmacomechanical
techniques during lysis.
The goal of mechanical or pharmacomechanical thrombolysis is to shorten thrombolysis times.
The benefits include restoring blood flow acutely for those with severe limb-threatening
ischemia, reducing the length of or eliminating lytic infusions, and reducing the cost of lytic
therapy by reducing drug utilization and shortening intensive care unit stays. The rheolytic
AngioJet catheter (Possis Medical, Minneapolis, MN) is the only mechanical device approved in
the United States for use as a thrombolytic catheter in the peripheral arterial system. The
catheter system creates turbulence at the catheter tip, creating a Bernoulli affect that
mechanically breaks down acute thrombus and facilitates the aspiration of a portion of the
treated thrombus. An advantage of this device over other mechanical devices is that mechanical
thrombolysis occurs without direct contact to the vessel wall, which can lead to intimal injury.
It is reported that when the rheolytic catheter is used to treat patients with lower extremity
acute ischemia, complete to partial thrombolysis is achieved in >80% of patients, and complete
or near-complete lysis is achieved in 60% to 70% of patients. These same studies report,
however, that adjunctive catheter-directed thrombolysis was initiated in 37% to 58% of patients
(101, 102, 103). From a practical standpoint, day-to-day clinical practice will find that rheolytic
catheter treatment is most often adjunctive to catheter-directed pharmacological lysis, and that
rheolytic catheter treatment is commonly used before, during, and in concluding catheter-
directed thrombolytic therapy. In addition, the AngioJet catheter can be used while
simultaneously infusing a lytic agent, that is, pharmacomechanical thrombolysis, which can
enhance the efficacy of this type of treatment. A mixture of 1 to 10 mg rt-PA/50 mL normal
saline can be infused via the AngioJet catheter depending on the specific needs of the patient,
with higher concentrations in settings of more severe ischemia.
Another simple mechanical technique for restoring blood flow in acute occlusions is suction
catheter thrombectomy. This technique is particularly useful for the removal of embolic material
that is resistant to thrombolytic agents or mechanical forms of lysis. This can occur when large
emboli from a cardiac source containing more chronic elements are resistant to lysis or when
endovascular procedures such as balloon angioplasty are complicated by the embolization of
atheromatous material. In both instances pharmacologic lytic treatment alone will require very
protracted infusion or may prove to be altogether ineffective. Multiple reports demonstrate the
effectiveness of this strategy in these and other instances (104, 105, 106). Large-bore guiding
catheters that maximize inner diameter size offer the most simple and effective tool for
aspirating material.
Patient Follow-up
Routine follow-up is recommended for all patients undergoing surgical or endovascular
treatment. The follow-up interval is nonuniform and varies from physician to physician. At our
institution we base the initial follow-up on the extent of disease and success of initial treatment.
For example, focal aortic or common iliac artery stenosis treated with simple angioplasty or
stenting will have a high primary patency rate and short-term interval surveillance may be
unnecessary. In this instance, follow-up at 6-month intervals for a total of 2 years is appropriate
and is our protocol. If the lesion morphology is extensive and the patient was treated with
endovascular means, we see the patient in our office in 1 month for history and physical
examination and repeat duplex vascular imaging examination including rest and postexercise
ankle-brachial indexes. If the lesion is focal and treatment shows good postoperative
morphology (no significant recoil or dissection), then we see the patient for follow-up at 3
months.
In general, patients with who have undergone iliac revascularization are seen for follow-up at 6-
month intervals. Those patients who have undergone femoropopliteal or tibial vessel
revascularization are seen at 3-month intervals for the first year and at 6-month intervals
thereafter. Limb salvage patients are often seen more frequently depending on the severity of
the presenting symptoms. With each office visit noninvasive vascular duplex imaging is
performed including rest and stress ankle-brachial indexes. Early diagnosis of recurrent
stenoses will lessen the risk of extensive revascularization procedures, such as thrombolysis,
and will allow reintervention on an outpatient basis in most cases.
New Endovascular Therapies

Stent-Grafts for Occlusive Peripheral Vascular Disease
Stent-grafts are self-expanding metal stents covered with a semipermeable or nonpermeable
material. Recently stent-grafts have been used in the treatment of long-segment disease of the
SFA and popliteal artery in hopes of improving patency. The reported data have been mixed in
terms of favorable results. Patency may be in part graft material dependent. Dacron-coated
stents have poor results in the SFA and illicit an inflammatory reaction, with fever and pain that
have become know as postimplantation syndrome. Recent trials with Dacron-coated stents
have reported patency rates as low as 23% in 1 year, with a high early thrombosis rate (107).
The most common stent-grafts available today use a Nitinol stent with an inner layer of thin
expanded polytetrafluoroethylene, with improved patency rates. Debate is ongoing as to
indication for use, whether there is improved durability compared with traditional stents, and
whether stent-grafts increase the risk for limb-threatening ischemia in the event of graft failure.
Proponents of stent-grafts claim that the covering prevents neointimal ingrowth through the
interstices of the stent, an advantage that theoretically improves durability. Opponents argue
that the covering blocks important collateral arteries arising from the stented vessel, whereas
bare metal stents usually preserve collateral arteries. Furthermore, opponents argue that
blocking collateral arteries increases the risk of stent-graft thrombosis and also increases the
risk of acute limb threatening ischemia in the event of stent thrombosis. Limited single-center
studies have shown a low incidence of acute thromboses in the treatment of peripheral arterial
occlusive disease (108, 109, 110, 111). However, studies evaluating covered stent-grafting for
popliteal aneurysms have reported stent-graft thromboses in 20% to 22% of the procedures at
1 year (112,113). Despite the debate, all agree that treatment of a thrombosed stent-graft is
time-consuming and costly, whereas treatment of a stenotic bare stent can be performed on an
outpatient basis, with little patient risk and expense.
Cutting Balloon
The cutting balloon (Boston Scientific, Boston, MA) was originally developed and used to treat
coronary stent restenosis (114,115). Three or four microblades or atherotomes, attached in
longitudinal fashion on the balloon, cut directly into the stenotic lesion during inflation. (114,116).
It is believed that the microblades penetrate directly into the fibroelastic layer of neointimal
hyperplasia and enable effective dilatation and intimal disruption requiring less relative wall
tension (116). As a result, this technique effectively treats a particular
stenosis with less neural barotrauma than conventional angioplasty (116,117). In one study
cutting balloon angioplasty was used to successfully treat popliteal and infrapopliteal vessels for
symptomatic limb ischemia. In this report a technical success rate of 100% and a 1-year limb
salvage rate of 89.5% were reported (118). A second study that examined the use of the
cutting balloon to treat anastomotic stenotic lesions in lower extremity bypass grafts revealed a
superior long-term patency rate in comparison to conventional angioplasty (116).
Besides the theoretical advantages of decreased barotrauma, the cutting balloon offers the
advantage of an alternative treatment when conventional angioplasty fails. This may be
especially attractive in situations when other alternatives such as stenting are less attractive.
For instance, the cutting balloon may be of benefit in the common femoral artery, where
stenting will obviate the use of this vessel for future vascular access or bypass grafting. The
device may also have an advantage over stenting in the popliteal artery, where the physical
stresses can lead to stent failure. Disadvantages of the cutting balloon include the limited
offering of balloon lengths, with the longest cutting balloon being 2 cm. This limits the utility of
the balloon in the peripheral system, where lesions can be several centimeters in length.
Additionally, the atherotomes add to the rigidity of the balloon, making this devise difficult to
pass through tortuous vessels, hence the relatively shorter balloon lengths.
Cryoplasty
Endovascular cryotherapy, or Cryoplasty (Boston Scientific, Boston, MA), combines the dilation
force of angioplasty with rapid freezing of the vessel wall (119). Nitrous oxide is delivered
through the balloon, lowering the interface layer temperature between the balloon and the
vessel wall to -10C over a depth of 500 m (120,124). Cryotherapy is able to induce
apoptosis (programmed cell death) in smooth muscle cells as well as other cell lines that
contribute to neointimal hyperplasia and restenosis (121,122). One study evaluating the use of
cryoplasty for the treatment of femoropopliteal arterial disease reports an initial technical
success rate of cryoplasty at 85.3%, with a low dissection rate of 6.9% (122,124,125). The 9-
month clinical patency rate was 85.3% (119,121,122). As with the cutting balloon, cryoplasty
provides a possible alternative to stent placement in those areas where stent placement is
unfavorable. Other alternative uses include the treatment of neointimal hyperplasia that occurs
within the femoropopliteal and infrapopliteal vessels.
Re-entry Catheters
Re-entry catheters are designed to facilitate controlled passage into the true arterial lumen
after subintimal guide-wire passage during recanalization procedures (123). Two catheters are
currently available: the Pioneer catheter (Medtronic, Inc., Santa Rosa, CA), which utilizes
intravascular ultrasound guidance, and the Outback catheter (Cordis Corp., Miami, FL), which
uses fluoroscopic guidance (123,124). In both instances the catheter is positioned within the
subintimal space distal to a chronic occlusion. The catheter is then directed toward the true
lumen utilizing either ultrasound or fluoroscopy. A small canula is then advanced toward the
lumen of the vessel to gain access to the more distal vascular bed. A guide wire is then
advanced from the catheter into the true lumen, allowing secure access. Limited published data
report a technical success rate of 80% to 100% in crossing the desired occluded segment
(123,124).
Atherectomy Catheters
Atherectomy catheters use a small rotating blade to cut and remove atheroma from diseased
arteries (125). The theoretical advantages of atherectomy over conventional angioplasty include
(1) reduced restenosis rate by debulking atheromatous mass, (2) additional therapeutic options
for lesions not amenable to angioplasty alone, and (3) increased immediate technical success,
given the absence of subintimal dissection and local barotrauma (125). The only atherectomy
catheter currently available is the SilverHawk Plaque Excision System (FoxHollow Technologies,
Redwood City, CA), which is available in varying sizes suitable for infra-inguinal use (126).
Previous devices used over the past 15 years (Simpson Atherocath, Auth Rotablator) resulted
in patency rates lower than those for angioplasty or stenting alone (126). Limited published
data on the rotational atherectomy catheter are currently available; however, early results are
promising, with 12-month patency rates of between 80% and 88% (126,127).
CONCLUSION
Optimizing therapy for atherosclerotic PAD will continue to provide a challenge as the
population ages and greater numbers of patients seek treatment. Clearly, this systemic disease
is best prevented by managing the multiple risk factors and adopting healthier lifestyles.
However, once patients have developed symptoms attributable to specific vascular beds or
focal lesions, treatmentwhether surgical or endovascularshould be tailored exquisitely as
described in this chapter and management should include adequate long-term follow-up and risk
factor modification.
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> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 20 - Interventions in Iliac
Artery Aneurysms
Chapter 20
Interventions in Iliac Artery Aneurysms
Renan Uflacker
Endovascular treatment of iliac artery aneurysms (IAAs) is currently a viable alternative to open
surgery. A number of procedures are available, and the combination of these procedures and
selection of the proper devices is based on the understanding of issues pertinent to IAA and
knowledge of iliac arterial anatomy. Planning for the procedure is necessary and a basic
knowledge of issues related to the IAA classification is required. Imaging now plays a
significant role in the understanding and mapping of the iliac arteries, as well as the definition of
the vascular anatomy and relationship of the vessels with the surrounding structures.
Experience is still somewhat limited, but there is acceptance that endovascular treatment for
IAAs is safe, effective, and durable. The evolution of the available devices for treatment of IAAs
has lagged behind the development of devices for abdominal aortic aneurysm (AAA) repair;
only recently have branched endografts for maintenance of the patency of the internal iliac
arteries been introduced, but they are not yet readily available. Larger studies, with longer
follow-up times, will be necessary to prove that all those options may in fact benefit the patients
with IAAs.
Involvement of the iliac arteries is seen in 10% to 20% of patients with AAA (1). However,
isolated IAAs are rarer, with a reported prevalence of 0.03% based on autopsies (2,3), but
more frequent in the elderly male population. The common iliac artery and the internal iliac
artery are the most common sites, and the external iliac artery is a less frequently affected site.
Enlargement of the common iliac artery to 15 mm should be considered an aneurysm. The risk
of rupture increases with the aneurysm size (4), and repair should be pursued if the IAA
reaches a size >30 to 35 mm in diameter (2,5,6).
Conventional surgical treatment of IAA is associated with a mortality rate ranging from 7% to
11% for elective treatment and a mortality rate of 50% for emergency surgery (5). Several
potential problems may be associated with open surgery, including ureteral laceration, venous
lesion, intestinal ischemia due to manipulation or bilateral ligature of the iliac artery, buttock
claudication, infection, and erectile dysfunction.
Atherosclerosis is the most common etiologic factor, but other causes include trauma, infection,
dissection, repetitive vigorous exercise with pelvic trauma, anastomotic graft failures, and
connective tissue disorders (7). Rupture is one of the most common complications of the
internal iliac artery aneurysms and may present as rectus sheath hematoma and/or
gastrointestinal bleeding. Common iliac aneurysms may also present as pelvic or psoas
hematomas. Besides the obvious risk of rupture, multiple other complications or symptoms may
develop due to external compression of surrounding organs and structures, including neurologic,
genito-urologic, and gastrointestinal problems (5,8). Ureteral stenosis is frequently associated
with peri-aneurysmal fibrosis, in addition to compression. Venous compression may cause leg
swelling, cellulitis, and deep vein thrombosis.
Buildup of thrombus within the IAA and atherosclerosis may cause stenosis and obliteration of
the downstream flow either to the lower extremity or to the territory of the ipsilateral internal
iliac artery. In such circumstances, it may be hard to completely evaluate a common iliac artery
stenosis within an IAA by angiography alone if the external wall of the aneurysmal vessel is not
visualized angiographically by the calcifications or by some form of axial imaging.
We reviewed 138 English-language articles on IAA published between 1982 and 2003. We
excluded the articles about AAA and repeated series. Twenty-five articles reporting on 665
patients with 877 IAAs were encountered. Ninety-seven percent of the reported cases were
atherosclerotic, 2.4% infectious, and 0.6% due to other causes., IAAs were located in the right
common iliac artery in 44.6% of cases, the left common iliac artery in 35%, the right internal
iliac artery in 8.5%, the left internal iliac artery in 7.7%, the right external iliac artery in 2.1%,
and the left external iliac artery in 2.1% (Table 20-1). In our review, the number of IAAs ranged
from 1.3 to 2.7 per patient, and there were nine males to one female. Occurrence was mostly
in the 70th decade. No reports of rupture were found in lesions <3 cm in diameter. Both open
surgery and endovascular repair of IAAs were technically successful, but the open technique
was linked to a higher morbidity and mortality (Table 20-2). The endovascular technique had
lower early complication rates but a significantly high late complication rate and a greater
number of additional procedures.
DIAGNOSIS AND IMAGING OF ILIAC ARTERY ANEURYSMS

Clinical findings are scarce in cases of IAAs except when a complication, such as urinary
obstruction, vascular compression, or rupture, is present. Most IAAs are incidental findings
during evaluation of the abdomen and pelvis for other problems. Imaging of IAAs is paramount
for the diagnosis and fundamental before a decision is made for endovascular treatment. The
proximal and distal necks of the aneurysms should be clearly depicted, as well as the size and
relationships of the aneurysm sac and surrounding structures. Currently, computed tomography
(CT) angiography performed with spiral, multidetectorarray CT scanners, should be the
standard for initial evaluation (Fig. 20-1A). Although magnetic resonance (MR) angiography can
also give a clear demonstration of the lesion, we prefer CT angiography with two-dimensional
(2D) and 3D image reconstruction (Fig. 20-2). We reserve MR angiography for patients with
renal insufficiency or contrast allergy.
Angiography continues to be the gold standard for IAA evaluation, particularly when performed
with a calibrated catheter,
which usually precedes the performance of the endovascular therapeutic procedure.
Angiography, however, is limited in visualization of the lumen of the aneurysm, and in most
cases, it is not able to properly identify either the presence of thrombus in the landing areas for
the stent or the exact external diameter of the aneurysm (Fig. 20-1B).
TABLE 20-1 LOCATION OF ILIAC ARTERY ANEURYSMS: REVIEW OF 25
ARTICLES AND 665 PATIENTS
Distribution Percentage
Right common iliac 44.6
Left common iliac 35.0
Right internal iliac 8.5
Left internal iliac 7.7
Right external iliac 2.1
Left external iliac 2.1
Intravascular ultrasound is a more recent addition to the armamentarium for endovascular

evaluation of the target vessels, and is able to identify with rather precise accuracy the internal
diameter of the vessel and the aneurysm and the thickness of the vessel walls. Excellent
assessment of the aneurysm neck is also provided by intravascular ultrasound technology, but
the overall diameter of the aneurysm is not always properly depicted.
MORPHOLOGIC CLASSIFICATION OF ILIAC ARTERY

ANEURYSMS
IAAs can be classified in common IAAs and internal IAAs. In addition, although there is a
frequent association between the two locations, often they are isolated and require separate,
independent treatments. There are at least two classifications for IAAs in the recent literature
(9,10), based on the vascular anatomy and working treatment.
Sakamoto's Classification (9)

Type I. IAAs in the internal iliac artery that are far enough (>2 cm) from the vessel origin to
allow proximal embolization of the internal iliac artery segment (Fig. 20-3).
Type II. IAAs in the internal iliac artery that are too close to the ostium of the vessel to allow
embolization of the internal iliac artery segment (Fig. 20-4).
TABLE 20-2 COMPARATIVE COMPLICATIONS IN TREATMENT OF ILIAC
ARTERY ANEURYSMS WITH OPEN SURGERY VERSUS ENDOVASCULAR
SURGERY: REVIEW OF 25 ARTICLES AND 665 PATIENTS
Endovascular
Open surgery p
surgery
Surgical mortality 2.9% 0.6% 0.7
Late mortality related to 0.7% (2 ruptures, 1 0.5% (1

1
IAA infection) rupture)
Emergency surgical Not

31% (47/149 cases) 0 (2 cases)
mortality comparable
FIGURE 20-1. A: CT angiogram of the pelvis in a patient with bilateral internal iliac
aneurysms. Note the large size of the right internal iliac aneurysm with a small vascular
lumen. B: Pelvic angiogram of the same patient depicting the lumen of the bilateral internal
iliac artery aneurysms (IAAs) but failing to show the true size of the aneurysm, especially
on the right side. Note displacement of the external iliac artery by the IAA mass.
FIGURE 20-2. CT angiogram with 3D reconstruction of a patient with a small AAA with
significant bilateral common iliac artery aneurysms and a large left internal artery
aneurysm.
FIGURE 20-3. A: Angiogram of bilateral IAAs in the internal iliac arteries from the origin of
the internal iliac artery extending to the bifurcation, allowing proximal embolization of the
internal iliac artery segment. The aneurysm caused right ureteral compression with
hydronephrosis. Note the barely visible ureteral stent. B: Selective catheterization and
angiogram of the right internal iliac artery, from a contralateral approach, showing the
lumen of a much larger aneurysm, not visualized by the angiogram. C: Iliac artery
angiogram after embolization of the right internal iliac artery with total occlusion. Note the
large number of coils used for the embolization. D: A balloon-expandable covered stent
(Atrium) was placed to exclude the small right common iliac artery aneurysm and cover the
origin of the right internal iliac artery. Note the right ureteral stent, previously placed to
decompress the kidney collecting system. E: Final iliac angiogram showing improvement of
the right common iliac artery aneurysm and totally excluded right internal iliac artery.
Type III. Common IAAs, located far enough from the aortoiliac bifurcation to allow placement of
a straight stentgraft (Fig. 20-5).
Type IV. Common IAAs, too close to the aortoiliac bifurcation, that do not allow placement of a
straight covered stent or stent-graft (Fig. 20-6).
Type V. Common IAAs or internal IIAs that develop after conventional AAA repair with a
bifurcated graft (Fig. 20-7).
Fahrni's Classification (10)

Type 1A. Common IAA with a proximal neck and distal neck allowing the use of a straight
covered stent, which may require embolization of the internal iliac artery (Figs. 20-8 and 20-9).
Type 1B. Common IAA, extension of an AAA or not, without a proximal neck, requiring
correction with a bifurcated aorto-iliac stent-graft (Figs. 20-10 and 20-11).
Type 2A. Internal IAA with a wide ostium, requiring a covered stent to bridge the common iliac
artery to the external iliac artery to exclude the internal iliac artery aneurysm, with distal
embolization of the internal iliac artery (Fig. 20-12).
Type 2B. Internal IAA with a long enough proximal neck to allow embolization of the proximal
arterial segment and the distal arterial segment (Fig. 20-3).
Type 2C. Internal IAA with a short proximal neck requiring embolization of the whole aneurysm
sac (Fig. 20-4).
FIGURE 20-4. A: Iliac artery arteriogram showing the conventional aortobiiliac graft
bypass and a large internal iliac artery aneurysm. There is also an anastomotic aneurysm
on the left side. B: Embolization of the aneurysm with coils was performed, with total
exclusion of the aneurysm sac. No stent-graft was felt to be necessary at the time.
FIGURE 20-5. A: Angiogram of the iliac arteries showing a left large massive common iliac
artery that had been rapidly expanding for the last couple of years. B: Selective left
common iliac arteriogram showed the aneurysm to extend to the bifurcation of the common
iliac and involve the origin of the internal iliac, which showed a stenosis. C: Selective
catheterization of the left internal iliac was performed and the artery was embolized with
coils, as shown by the angiogram. D: Pelvic arteriogram showing the aneurysm just before
repair with a covered stent. Note the tortuosity of the external iliac. E: Pelvic arteriogram
showing the excluded aneurysm following placement of a Viabahn device, connecting the
proximal neck and the external iliac artery.

FIGURE 20-6. A: Aortic and pelvic angiogram showing a relatively normal infrarenal aorta,
but a large aneurysm of the right common iliac artery was evident. The left common iliac
artery was ectatic but still acceptable. B: As part of the management of the patient a
bifurcated aorto-iliac stent graft was planned, extending into the right external iliac artery.
Embolization of the right internal iliac artery became necessary and was performed with
coils. C: Final aortogram shows a patent AneuRx-bifurcated stent-graft with exclusion of
the iliac aneurysm and the occluded right internal iliac artery.
FIGURE 20-7. A: CT angiogram of the iliac arteries showing significant residual aneurysms
in both native common iliac arteries. Note the patent aorto-iliac graft just in front of the
aneurysms. B: Angiogram of the pelvic vessels showing the aorto-iliac graft properly
anastomosed to the external iliac arteries and retrograde filling of the native common iliac
arteries and the large saccular aneurysms. C: Oblique view of the pelvic vessels showing
the residual aneurysms at the end of the common iliac arteries and the connections with
the internal iliac arteries. D: Coil embolization of both aneurysms was performed, to no
avail. Note the uncovered stent trying to connect the common iliac artery to the internal iliac
artery on the right. E: Since embolization did not work well to exclude the aneurysms, an 8
mm 60 mm Wallgraft was placed, connecting the right common iliac artery to branches
of the internal iliac artery. The device is shown just predelivery. F: Angiogram after
deployment of the covered stent showing continuity of the right common iliac artery with
distal branches of the internal iliac artery. G: Placement of an 8 mm 60 mm Wallgraft
connecting the left common iliac artery to branches of the internal iliac artery. Picture taken
during balloon dilation. H: Final arteriogram showing patency of the aorto-iliac graft and
patency of both internal iliac arteries, with total exclusion of the aneurysms.
FIGURE 20-8. A: CT angiogram of the pelvic vessels showing a large left common iliac
artery aneurysm. B: Pelvic arteriogram showing a large saccular aneurysm in the left
common iliac artery aneurysm with an adequate proximal neck and extending to the
bifurcation and involving the internal iliac artery. The right common iliac artery is also
slightly aneurysmal. C: The left internal iliac artery was embolized with coils, distal to the
aneurysm. Note that there is not cessation of flow distally. D: A Wallgraft was placed but
the aneurysm was not excluded despite multiple balloon dilatations, due to a proximal type
I endoleak. E: CT angiogram, 1 month after treatment, showing a persistent type I
endoleak with a channel within the aneurysm sac. F: Three-dimensional reconstruction of
the CT angiogram shows the persistent endoleak draining into the left internal iliac artery,
despite the previous embolization. G: Angiogram was performed to possibly treat the
endoleak. Note the channel within the aneurysm sac draining the internal iliac artery, from a
proximal leak. H: A Palmaz stent was placed within the proximal segment of the Wallgraft,
with successful closure of the endoleak and exclusion of the aneurysm.
FIGURE 20-9. A: CT angiogram of the pelvic vessels showing a large aneurysm of the
right common iliac artery. Note the calcified small aneurysm of the left internal iliac artery.
B: Angiogram of the pelvis showing a small AAA and a large right iliac artery aneurysm.
Note the left internal iliac artery aneurysmal dilatation, which was not treated. C:
Angiogram post-stent-graft placement showing total exclusion of the aortic AAA and the
right iliac aneurysm. The right internal iliac artery was embolized. D: CT angiography
following stent-graft treatment showed total exclusion of the iliac artery aneurysm. E: The
6-month follow-up showed significant shrinkage of the right iliac aneurysm.
FIGURE 20-10. A: Abdominal aortogram showed a large AAA extending to the left
common iliac artery. B: Aortogram post repair of the AAA and iliac aneurysm showed
exclusion of the AAA and iliac aneurysm. The left internal iliac artery was embolized with
coils. This patient did have a type II endoleak, which was embolized by translumbar
access.
FIGURE 20-11. A: Abdominal aortogram showed a large AAA, extending to both common
iliac arteries all the way to the bifurcation of the iliac arteries. Note the internal iliac arteries
involved by the iliac aneurysms. B: Post-stent-graft placement angiogram showed total
exclusion of the AAA and iliac aneurysms. This patient did present with a type III endoleak
from the right ipsilateral extension. The endoleak was treated with coils and an additional
covered stent placed within the extension.
FIGURE 20-12. A: CT angiogram showed the large left internal iliac aneurysm, with a large
external diameter and a smaller lumen. There was significant compression of the left
ureter, with hydronephrosis and kidney infection. B: Three-dimensional reconstruction of
the CT angiogram with demonstration of the small AAA of the distal abdominal aorta and
bilateral common iliac artery aneurysms, as well as the left internal iliac artery aneurysm
described above. C: Pelvic angiogram showed the small ectasia of the distal abdominal
aorta and bilateral common iliac artery aneurysms, as well as the left internal iliac artery
aneurysm. D: Embolization of the left internal iliac artery aneurysm was performed but was
not enough to completely occlude the internal iliac aneurysm. A follow-up CT angiogram of
the pelvis showed persistent patency of the lumen of the internal iliac aneurysm. Note the
pack of coils. E: Maximum intensity projection reconstructions of the CT angiogram
showed persistent hydronephrosis of the left kidney, despite the embolization. Note the
marked compression of the urinary bladder. F: A decision was made to intervene
surgically, resect the internal iliac artery aneurysm, and treat the aortic and common iliac
aneurysms with an endograft. G: Angiogram of the abdominal aorta and iliac vessels after
placement of an Excluder stent-graft, which excluded the AAA and both common iliac
arteries. Note that the right internal iliac artery was embolized and the left internal iliac
artery was surgically ligated.

INDICATIONS FOR TREATMENT
Patients without Compressive Symptoms
In patients at high risk for conventional surgery, endovascular treatment is clearly indicated, and
selection of the technique and devices requires tailoring to the specific anatomy of the patient.
Patients at low risk and without compressive symptoms can be treated by either technique, and
selection of the repair methodology will be based mostly on the anatomy of the lesion and size
of the IAA. Regression of the aneurysm size is encountered in the majority of patients (Fig. 20-
9). Younger patients who are good surgical candidates should be treated preferably by open
surgery, since the long-term results of stentgrafting are still not fully understood.
Patients with Compressive Symptoms

Symptomatic patients with compression of surrounding structures, in principle, can be treated
by either technique. However, in cases of venous or ureteral compression embolization of the
aneurysm sac or exclusion of the aneurysm by a stent-graft may not decompress the aneurysm
adequately and may not relieve the obstruction in a timely fashion (Fig. 20-12). Thrombosed
iliac aneurysms treated by the endovascular approach may shrink over a period of time (11)
(Fig 20-9)again, an important consideration when the compressive symptoms are urinary or
neurologic.
Infected Aneurysms or Pseudoaneurysms

Infected IAAs may progress rapidly to rupture if not treated. Resection of the aneurysm or
ligation of the vessel is mandatory, with creation of an extra-anatomic bypass, which involves
two major procedures plagued by the risk of infection. Selected cases can be treated with
endovascular grafts when backed up by aggressive antibiotic therapy for prolonged periods of
time (12,13), especially if there are no other options available for the specific patient (Fig. 20-
13). In some instances of pelvic infection and radiation arteritis, it may be better to place a bare
stent and temporarily occlude the parent artery of the aneurysm (false aneurysm) with an
occlusive balloon or coil embolization (Fig. 20-14).
Traumatic and Iatrogenic Iliac Artery Aneurysms

Pelvic trauma is a relatively frequent occurrence in modern society, and vascular rupture or
laceration may be a dramatic consequence of pelvic fractures and dislocations (14). Some of
the pelvic arteries run very close to the pelvic bone surface or are located in a region prone to
fractures and diastases, causing stretching or transection of the artery. The superior gluteal
artery is one of those arteries; crossing from the inside of the pelvis to the gluteal region
through the greater sciatic foramen, in contact with the greater sciatic notch, it is prone to
laceration following the displacement of the fractured bone (Fig. 20-15). Posttraumatic pelvic
bleeding is a potentially catastrophic event that is difficult to manage surgically. Open surgery is
usually not an alternative to polytraumatized patients, due to poor neurologic status and or
multiple organ trauma. Percutaneous angiography and embolization are minimally invasive
procedures and can be performed with local anesthesia. The diagnostic angiogram serves as
the roadmap to find the bleeding source and allows the catheter to serve as the therapeutic
tool. Intra-arterial embolization with Gelfoam or coils is the treatment of choice and is
successful in almost 100% of cases. However, pelvic embolization for traumatic
pseudoaneurysms cannot be taken lightly and gluteal muscle and skin necrosis may develop in
about 10% of patients, particularly if smaller particles are used to embolize the vessel distally
(14). Blunt low abdominal trauma, particularly in children, may cause laceration, bleeding, and
pseudoaneurysms of the common iliac arteries, even without pelvic fractures (15).
Iatrogenic iliac artery pseudoaneurysms may result from pelvic radiation therapy or open
surgery for unrelated problems, such as gynecologic cancer, bladder cancer, and kidney
transplant (16) (Fig. 20-16).
TREATMENT OF IAAs
Modern endovascular therapy for IAAs should use all the resources available for minimally
invasive procedures. Most of the procedures can be performed under local anesthesia, using
percutaneous technique or minimal femoral cutdown. As IAAs are part of arteries feeding the
pelvis and the lower extremities, the aim is preservation of the distal flow, keeping the parent
vessel open with a stent-graft or covered stent.
All cases should have an angiogram including the aorta and iliac vessels to roadmap the
branches and the location of the aneurysms and, most importantly, to identify and assess the
proximal and distal necks. Performing the diagnostic angiogram several days prior to the
therapeutic procedure will allow some degree of planning and ordering of adequate devices,
which may not be readily available in the proper sizes and lengths.
Embolization
Embolization is an integral part of the management of IAAs, using selective catheterization of
the vessels to be sacrificed for angiograms and delivery of the embolic materials. Gianturco
coils (Cook Inc., Bloomington, IN) are the most used embolic materials in the pelvic arteries
(Fig. 20-17), although other large occlusive devices, such as detachable balloons and
cyanoacrylate glue, can be used with advantages in specific situations. The main difference
between coils and detachable balloons is related to the capability of the latter to use flow to
direct the balloon to the site of desired deployment.
Coil embolization should target a specific vessel or branch and the size of the coil has to be
compatible with the diameter of the artery to be occluded, oversizing the vessels by about 10%
to 15%. There are several types of embolic coils, including detachable coils. IAAs are usually
embolized with 0.035-in.-wire-diameter coils ranging in fully deployed coil diameter from 5 to 20
mm. The large diameter and longer detachable coils are more useful to fill the aneurysm sac of
the internal iliac artery. In types I and II (9) filling of the sac cavity by coils is in general
associated with embolization of the outlet vessel, and when feasible, the inlet vessel should be
selectively occluded by coils as well. Coverage of the orifice of the internal iliac artery by a
stent-graft is necessary when the aneurysm is not far enough from the origin of the artery and
therefore, not amenable to treatment only by embolization. However, embolization of the distal
segment of the internal iliac artery becomes necessary in cases of isolated internal iliac
aneurysms, which are not amenable to stenting due to the location of the aneurysm sac. In
cases where there is a common IAA extending to or including the orifice of a normal internal
iliac artery, aneurysm type III or IV (9) (Figs. 20-18 and 20-19), embolization is necessary to
prevent backflow into the common iliac aneurysm, after exclusion of the aneurysm by a covered
stent, avoiding a type III endoleak (Fig. 20-8).
FIGURE 20-13. A: Left external iliac artery angiogram showed mycotic aneurysm following
a left hip infection and surgery. B: Late phase of the angiogram showed the large mycotic
aneurysm and filling of the distal external iliac artery. A long Wallgraft was placed in the left
distal external iliac artery and dilated with a 6-mm balloon. C: Postgrafting angiogram
showed total exclusion of the aneurysm with excellent patency of the distal femoral artery.
FIGURE 20-14. A: Pelvic angiogram showed a left external iliac pseudoaneurysm (possibly
mycotic) related to a gynecologic cancer surgery followed by radiation therapy. Note the
stenosis of the parent vessel. B: Due to the infectious process, a decision was made to
use a bare Wallstent to bridge the stenotic segment and occlude the artery with an
occlusion balloon for 20 minutes to promote thrombosis of the aneurysm, which was
successful. Several months later, the patient developed a similar pseudoaneurysm in the
right iliac artery.
Stent-Graft Placement
Once the location, extension, and anatomical characteristics of the IAA are defined, treatment
with a stent-graft should be preferentially pursued. In types III and IV IAAs, the use of a stent-
graft is mandatory (Figs. 20-18 and 20-19). In type III, there is enough proximal neck (>2 cm)
to deploy a straighttube, covered stent that will bridge the normal proximal segment to the
distal normal segment, usually the external iliac artery. In these cases embolization of the
ipsilateral internal iliac is also performed. In type IV, there is not enough proximal neck, and the
aneurysm is too close to the aortic bifurcation to place a tubular stent-graft. In these cases, a
bifurcated aorto-iliac stent-graft needs to be fitted to bridge the infrarenal aorta to the
ipsilateral external iliac artery to the aneurysm, and to the contralateral common iliac artery,
with embolization of the ipsilateral internal iliac artery. Alternative endovascular treatment for
type IV aneurysms is an aorto-uni-iliac stentgraft, with blockage of the contralateral common
iliac artery with an arterial occluder and placement of a femoral-femoral bypass (Fig. 20-20).
Reconstruction of aneurysmal iliac arteries using stent-graft technology should follow the same
guidelines for AAA repair concerning access artery size, angle, presence of atherosclerotic
disease, and suitable landing zones. Landing zones of at least 15 mm are required. When
feasible, a percutaneous access should be chosen and the procedure can be done under local
anesthesia, with a small nick in the groin. Surgical cutdown is only necessary when more
extensive vessel calcification and tortuosity are present.
Cases of residual aneurysms of the iliac artery stumps in a cul-de-sac configuration or newly
developed para-anastomotic aneurysms following open AAA repair require a slightly different
approach. A para-anastomotic aneurysm can usually be treated with a straight covered stent,
with or without embolization of the internal iliac artery. The cul-de-sac common iliac stump
aneurysm receives retrograde perfusion, which may induce progressive dilatation. The option of
embolizing the postaneurysmatic segment of the internal iliac and the feeder external iliac
segment is useful, however, the size of these vessels may be quite significant and distal
catheterization for embolization across the aneurysm may be very challenging, requiring
embolization of the outlet, the aneurysm sac, and the feeding artery. When the cul-de-sac
aneurysm is bilateral, embolization of both internal iliac arteries may pose an ischemic risk for
the pelvic organs. A viable alternative to the embolization is retrograde catheterization of the
iliac stump, across the aneurysm sac, and antegrade catheterization of the internal iliac artery
with placement of a very flexible stent-graft such as a Wallgraft or Viabahn to bridge the
common iliac artery to the internal iliac artery (Fig. 20-7). Exclusion of the aneurysm is
achieved, and the stent-graft still maintains perfusion of the distal branches within the pelvis.
FIGURE 20-15. A: Pelvic arteriogram in a patient with pelvic trauma and active bleeding.
Note the small aneurysm in the left superior gluteal artery. All vessels are spastic due to
blood loss and hypotension. B: Selective left internal iliac arteriogram showing the
laceration pseudoaneurysm in the proximal segment of the left superior gluteal artery. C:
Selective angiogram of the left superior gluteal artery showing the pseudoaneurysm. D:
Embolization was performed with coils in the proximal segment of the superior gluteal
artery.
FIGURE 20-16. A: Right external iliac artery angiogram showed a large pseudoaneurysm,
following the explant of a transplant kidney, from the external iliac artery. B: Picture of the
area showed coils within the pseudoaneurysm, a Wallstent within the artery, and occlusion
of the artery flow with an occlusion balloon. C: Posttreatment angiogram showed
resolution of the pseudoaneurysm.
Follow-up
CT angiograms are usually performed at 30 days, and at 6-month intervals thereafter, to detect
possible endoleaks, thrombosis, or migration. Common iliac aneurysms may show significant
shrinkage over a period of 6 to 12 months (Fig. 20-9), however, internal IAAs treated with
embolization may take much longer to shrink and resolve compressive symptoms. The
presence of platinum or stainless-steel coils within the vessels or within the aneurysm cavity
may significantly deteriorate the CT image, making it more difficult to evaluate reperfusion
within the sac.
COMPLICATIONS OF ENDOVASCULAR THERAPY

Possible complications of treatments related to IAAs are rare but may be related to progress
of the disease or procedures used
for treatment. Thrombosis of the graft is a possibility following treatment of an IAA, and a
couple of causes should be carefully considered: First, all patients should have flow guaranteed
by opening the outflow of the iliac circulation, particularly to the lower extremity. Second, if
there is mismatch of the proximal and distal diameters of the necks of the aneurysm, a tapered
graft should be used to reduce excessive folding of the graft within the lumen.
FIGURE 20-17. A: Pelvic arteriogram showed a common left iliac artery aneurysm with a
proximal neck and extending to the bifurcation. B: Angiogram post embolization of the left
internal iliac artery. C: Poststent-graft angiogram showed resolution of the aneurysm with
exclusion. The internal iliac remained occluded. This patient had further dilation of the
proximal neck and open surgery was performed.
Catheterization of the iliac vessels with the large introducer systems of the stent-grafts may
cause plaque fragmentation, dissection, and arterial wall injury with laceration. Excessive
tortuosity, small size, and calcification are risk factors for injury. In most cases, placement of a
stent may solve the problem. Rupture of the iliac arteries may be resolved with a covered stent.
Embolization of the internal iliac artery preceding stentgraft placement is relatively safe and
effective (11) but may result in non-target-organ embolization, which may cause unanticipated
ischemia in other pelvic organs or ischemia in the lower extremity. Careful manipulation and
embolic materials properly selected for the target vascular bed are essential to prevent this
type of complication.
Internal IAA excluded by open surgery in conjunction with AAA repair caused buttock
claudication in 12% of cases and erectile dysfunction in 39% (17). Bladder dysfunction and
sacral ulceration may also be encountered after embolization
of the internal iliac arteries. Most series reflect the safety of unilateral internal iliac artery
sacrifice (18). Bilateral hypogastric artery occlusion, especially if not staged temporally, may
cause more significant complications, however, the incidence of claudication and impotence
remains significant, prompting some to recommend revascularization of at least one internal
iliac artery at the time of AAA repair to preserve pelvic arterial flow (19). Intentional internal iliac
artery embolization may be accompanied by significant morbidity and should be approached
with caution (20), and severe pelvic ischemia is more likely to occur after bilateral embolization
(21). The development of branched stent-graft devices should decrease the need for internal
iliac occlusion
FIGURE 20-18. A: Oblique iliac angiogram showing a large fusiform left common iliac
arteriogram, extending to the bifurcation of the iliac. B: Left common iliac artery angiogram
showed the extension of the aneurysm to the internal iliac, requiring embolization. C: Final
angiogram. The lesion was corrected with a bifurcated stent-graft extending to the left
external iliac artery. The left internal iliac was embolized.
Sigmoid and rectal ischemia may develop following internal iliac artery embolization, although
most patients can tolerate quite well the occlusion of one and sometimes both internal iliac
arteries, especially if the embolization is more proximal. Patency of the inferior mesenteric
artery in general secures adequate blood perfusion of the rectum, but in some cases when a
bifurcated stent-graft is used, the inferior mesenteric artery ostium will be covered and the
whole sigmoid-rectal circulation will depend on the superior mesenteric artery. In a large series
of patients operated for conventional AAA repair, the incidence of postoperative colonic
ischemia was 1.2% and surgical revascularization of the internal iliac arteries did not affect the
outcomes in this group of patients (22).
FIGURE 20-19. A: Pelvic arteriogram showing an AAA and massive bilateral iliac
aneurysms. Note the extreme tortuosity of the iliac arteries. B: Angiogram post-stent-graft
placement to repair the AAA and the iliac artery aneurysms. Note the crossing legs of the
graft and remaining tortuosity of the iliacs. C: Distal angiogram showing patency of the
iliacs and significant tortuosity.
Some guidelines for internal iliac artery embolization should be followed in an attempt to reduce
morbidity.
1. Preservation of one internal iliac artery or revascularization of one internal iliac artery
2. Proximal embolization
3. Preservation of the branches of the external iliac artery and common femoral artery, including
the profunda femoris artery
4. Study of the superior mesenteric artery/inferior mesenteric artery circulation to ensure
adequate perfusion of the colon
5. Occlusion tests, when necessary
CONCLUSION
Treatment of IAAs is safe and effective, although there are still questions regarding the long-
term efficacy of the devices. In general, most cases are feasible with the current technology,
provided the anatomy is carefully assessed. Complications are few and mostly preventable by
proper planning and technique and selection of adequate devices. The development of newer
devices with fenestrations and branches should reduce even further some of the complications
and facilitate the treatment of more difficult anatomies.
FIGURE 20-20. Posttreatment angiogram showed a patent aorto-uni-iliac stent-graft. Both
internal iliacs were embolized with coils and the left common iliac artery was occluded with
an arterial occluder. Note the femoral-femoral graft revascularizing the left leg circulation
(see Figs. 22-1A and B).
References
1. Drupski WC, Selzman CH, Floridia R, et al. Contemporary management of isolated iliac
aneurysms. J Vasc Surg. 1998;28:1-11.
2. Bunkwall J, Hauksson N, Bengtsson H, et al. Solitary aneurysm of the iliac artery system:
an estimate of their frequency of occurrence. J Vasc Surg. 1989;10:381-384.
3. Lucke B, Rea MH. Studies on aneurysms. JAMA. 1921;77:935-940.
4. Sekkal S, Cornu E, Christides C, et al. Iliac artery aneurysms: sixty seven cases in forty
eight patients. J Mal Vasc. 1993;18:13-17.
5. Richardson JW, Greenfield LJ. Natural history and management of iliac aneurysms. J
Vasc Surg. 1988;8:165-171.
6. McCready RA, Pairolero PC, Gilmore JC, et al. Isolated iliac artery aneurysms. Surgery.
1983;93:688-693.
7. van Sambeek MR, van Urk H. Endovascular treatment of isolated iliac artery aneurysms.
Eur J Vasc Endovasc Surg. 1998;15:91-92.
8. Sacks NP, Huddy SP, et al. Management of solitary iliac aneurysms. J Cardiovasc Surg
(Torino). 1992;33:679-683.
9. Sakamoto I, Sueyoshi E, Hazama S, et al. Endovascular treatment of iliac artery

aneurysms. Radiographics. 2005;25:S213-S227.
10. Fahrni M, Lachat MM, Wildermuth S, et al. Endovascular therapeutic options for isolated
aneurysms with a wording classification. Cardiovasc Intervent Radiol. 2003;26:443-447.
11. Sakamoto I, Mori M, Nishida A, et al. Coil embolization of iliac artery aneurysms
developing after abdominal aortic aneurysm repair with a conventional bifurcated graft. J
Endovasc Ther. 2003;10:1075-1081.
12. Sanada J, Matsui O, Arakawa F, et al. Endovascular stent-grafting for infected iliac
artery pesudoaneurysms. Cardio Vasc Intervent Radiol. 2005;28:83-86.
13. Adovasio R, Mucelli FP, Lubrano G, et al. Endovascular treatment of external iliac artery
injuries after hip arthroplasty. J Endovasc Ther. 2003;10:672-675.
14. Suzuki T, Shindo M, Kataoka Y, et al. Clinical characteristics of pelvic fracture patients
with gluteal necrosis resulting from transcatheter arterial embolization. Arch Orthop Trauma
Surg. 2005;125:448-452.
15. Milas ZL, Dodson TF, Ricketss RR. Pediatric blunt trauma resulting in major arterial
injuries. Am Surg. 2004;70:443-447.
16. Baltacioglu F, Cimsit NC, Cil B, et al. Endovascular stent-graft applications in iatrogenic
vascular injuries. Cardio Vasc Intervent Radiol. 2003;26:434-439.
17. Urayama H, Ohtake H, Katada T, et al. Exclusion of internal iliac arterial aneurysm
concomitant with abdominal aortic aneurysm. J Cardiovasc Surg (Torino). 1999;40:243-
247.
18. Rhee RY, Muluk, Tzeng E, et al. Can the internal iliac artery be safely covered during
endovascular repair of abdominal aortic and iliac artery aneurysms?. Ann Vasc Surg.
2002;16:29-36.
19. Morrissey NJ, Faries PL, Carrocio A, et al. Intentional internal iliac artery occlusion in
endovascular repair of abdominal aortic aneurysms. J Invas Cardiol. 2002;14:760-763.
20. Lyden SP, Sternbach Y, Waldman DL, et al. Clinical implications of internal iliac artery
embolization in endovascular repair of aortoiliac aneurysms. Ann Vasc Surg. 2001;15:539-
543.
21. Lin PH, Bush RL, Chaikof EL, et al. A prospective evaluation of hypogastric artery
embolization in endovascular aortoiliac aneurysm repair. J Vasc Surg. 2002;36:500-506.
22. Pittaluga P, Batt M, Hassen-Khodja R, et al. Revascularization of internal iliac arteries

during aortoiliac surgery: a multicenter study. Ann Vasc Surg. 1998;12:537-543.
> Table of Contents > Section III - Vascular Interventions > Part A: - Arterial Interventions > Chapter 21 - Drug-Eluting Stents in
Peripheral Vascular Disease
Chapter 21
Drug-Eluting Stents in Peripheral Vascular Disease
Lindsay Machan
A drug-eluting stent is a stent that is coated or embedded with single or multiple bioactive
agents. Following implantation, the therapeutic material is released locally into the vessel wall
adjacent to the stent as well as into the bloodstream It is ironic that stents have again become
a means by which local tissue growth can be modified; Charles R. Stent, an English dentist who
died in 1901, devised and lent his name to a curved mold first used as a scaffold to enhance
oral skin grafts (1). This chapter discusses only coated stents designed for the prevention of
restenosis, however, stents that are resistant to thrombosis or designed as reservoirs for the
release of agents such as vasodilators or chemotherapeutic agents into the downstream
vasculature have also been described (2).
Since U.S. Food and Drug Administration approval for coronary use in March 2003, drug-eluting
stents have made an impact on the practice of interventional cardiology similar in magnitude to
the impact of the introduction of angioplasty in the 1980s. Within 1 year of their introduction,
78.2% of coronary stents inserted in the United States were drug eluting, and both the total
number of endovascular coronary procedures and the proportion involving drug-eluting stents
have risen significantly since that time (3). Despite the broad acceptance by the cardiology
community, experience in the peripheral arterial circulation has been limited to date; two small
randomized multicenter studies and a number of observational single-center reports have been
published.
RESTENOSIS
Restenosis is defined as the recurrence of a vascular narrowing after an initially successful
revascularization. It can occur after any vascular intervention including balloon angioplasty (Fig.
21-1), atherectomy, or stent insertion (4) and is the major factor limiting the longevity of
endovascular procedures. Restenosis after percutaneous transluminal angioplasty is due to
elastic recoil, constrictive remodeling, and neointimal hyperplasia, but as stents essentially
prevent elastic recoil and vessel remodeling, neointimal hyperplasia is the principal component
of in-stent restenosis (5) (Fig. 21-2).
Neointimal hyperplasia (also called intimal or myointimal hyperplasia) is an overexpression of
the normal vascular healing process. Stent implantation results in disruption of the endothelium
and a local change in vessel compliance (stiffness). These in turn immediately stimulate a
healing response that is modulated by a complex interplay of events occurring in the lumen and
the vessel wall (6). On the luminal surface there is platelet activation and thrombus formation
prior to endothelial recoverage. Within the adjacent vessel wall there is acute inflammation,
granulation tissue formation, and the local release of chemotactic and growth factors and
oxygen-derived free radicals. In pathologic neointimal hyperplasia (as opposed to appropriately
modulated intimal hyperplasia occurring after a normal vessel response to injury), there is
excessive proliferation and migration of upregulated vascular smooth muscle cells and
oversecretion of an extracellular proteoglycan matrix. The ideal antirestenosis drug should
potently inhibit the overexpression of these processes yet still allow vascular healing (Fig. 21-
3). It is probable that certain drug/device combinations might be more effective in one area of
the body than another, as the degree to which the intimal hyperplasia lesion is composed of
vascular smooth muscle cells or proteinaceous matrix varies from vascular bed to vascular bed
(7).
In the literature, restenosis is broadly divided into two categories, angiographic and clinical
restenosis. In most clinical trials angiographic restenosis is defined as a recurrent narrowing
>50% (the incidence of angiographic restenoses of 51% may also be called the binary
restenosis rate). If the narrowing occurs within the stent lumen it is labeled in-stent restenosis
(Fig. 21-4A). If the narrowing is within the stent lumen or the 0.5-cm segment of artery
immediately proximal or distal to the stent, it is called in-segment restenosis (Fig. 21-4B).
Because patients with angiographic restenosis may be asymptomatic, many consider clinical
restenosis the more relevant term. There are multiple ways to define clinical restenosis
including recurrence of symptoms and a decline in noninvasive measurements. However, in the
drug-eluting stent literature the most popular measures used are the incidences of target lesion
revascularization (TLR rate), defined as the frequency of repeat procedure at the site of the
initial intervention, and target vessel revascularization (TVR). The latter refers to interventions
performed anywhere along the entire length of the vessel into which the stent was inserted.
DRUG-ELUTING STENTS
Drug-eluting stents are complex devices made of three components: the stent, a slow-release
polymeric coating (or equivalent) connecting the drug to the stent, and the drug itself.
Stents
To date, the vast majority of drug-eluting stents used in the coronary circulation and all stents
used in the periphery are conventional stents primarily designed to optimally traverse and treat
stenoses, with drug delivery a secondary consideration. On these stents, drugs are usually
applied as a thin layer on the surface of the stent opposing the vessel wall (abluminal surface).
There are coronary stents purposefully designed to enhance drug loading and delivery by
having laser-cut reservoirs or slots that act as receptacles for drugs and polymer (8).
FIGURE 21-1. Restenosis after balloon angioplasty. A: Eccentric superficial femoral artery
stenosis. Complete eradication was achieved by angioplasty. B: This smooth renarrowing
at the same site was demonstrated 3 months later.
Stent Coating
Finding suitable carriers for stent-based drug delivery may be the most challenging aspect of
drug-eluting stent development. The coating must be suitable for sterilization, be resistant to
abrasion or flaking during stent implantation and expansion, and provide controllable drug
release (both in concentration and time), all without thrombogenic or inflammatory effects on
the vessel wall. The most commonly used vehicles are nonerodable polymer coatings (Fig. 21-
5A), but others including phosphorylcholine, biodegradable, or bioabsorbable polymers and
ceramic layers have been developed (9). On the ZilverPTX stent (Cook Inc., Bloomington, IN),
a self-expanding Nitinol stent designed for peripheral vascular implantation, the drug paclitaxel
is directly applied to the stent surface without a polymer (Fig. 21-5B), relying on the markedly
lipophilic nature of paclitaxel to create adequate concentration and dwell time in the surrounding
vessel wall for the desired inhibitory effect (10).
FIGURE 21-2. Stent-induced neointimal hyperplasia. Cross section of uncoated arterial
stent (H&E stain). The lumen is narrowed by neointimal ingrowth. As the stent remains fully
expanded, elastic recoil or constrictive remodeling is not a component of in-stent
restenosis. (See the color insert.)
Drugs
A vast number of drugs have been evaluated as potential coatings for drug-eluting stents
(11,12). They may be generally classified on the basis of their mechanism of action as
immunosuppressive, antiproliferative, anti-inflammatory,
antithrombotic, modulators of extracellular matrix, or prohealing (Table 21-1). This classification
is somewhat arbitrary, as some agents may affect multiple steps in the restenotic process or
have very different mechanisms of action depending on the tissue concentration. At the time of
writing, two agents, rapamycin and paclitaxel, are approved for clinical use on coronary stents
in the United States and Europe, and two, zotarolimus and everolimus, are approved for
coronary use in Europe only. Rapamycin-coated balloon-expandable stents are the only drug-
eluting stents approved for a noncoronary indication; in Europe they are permitted for the
treatment of critical limb ischemia.
FIGURE 21-3. Ideal performance of a drug-eluting stent (H&E stain). Neointimal
hyperplasia is prevented and there is endothelial coverage of the stent tynes. (See the
color insert.)
FIGURE 21-4. Types of angiographic restenosis. A: In-stent restenosis. SFA arteriogram 6

months post insertion of a SMART stent demonstrating diffuse luminal narrowing due to
neointimal hyperplasia. Note the separation of the outline of the stent from the narrowed
arterial lumen. B: Insegment restenosis. Reconstructed maximum image projection from a
CT angiogram demonstrating a tight eccentric stenosis immediately proximal to (within 0.5
cm of) the right common iliac artery stent.
Sirolimus (Rapamycin)-Eluting Stents

Sirolimus (rapamycin; Wyeth, Ayerst, PA) is a macrolide antibiotic with potent
immunosuppressive activity. It was originally isolated in the mid 1930s from Streptomyces
hygroscopicus found in Easter Island soil samples (the island is called Rapanui by its natives,
hence the name rapamycin). Rapamycin diffuses into smooth muscle cells and binds to an
intracellular receptor, the FK506 binding protein. It inhibits cellular proliferation by blocking cell
cycle progression from the G1 to the S phase. After rapamycin was shown to profoundly inhibit
intimal thickening in animal models of vascular injury (13), multiple trials confirmed the efficacy
of rapamycin-coated coronary stents in humans (14,15). The largest was SIRIUS, a
prospective, randomized, 53-center U.S. trial comparing uncoated and rapamycin-coated Bx
Velocity stents (Cordis Endovascular, Miami, FL) in 1,100 patients with de novo coronary
lesions (16). At 8 months in-stent restenosis was 3.2% in the drug-coated group versus 35.4%
in the noncoated stent arm and in-segment restenosis was 8.9% versus 36.3% (p <0.001).
TABLE 21-1 DRUGS AND BIOLOGICALLY ACTIVE AGENTS USED ON

STENTS TO PREVENT RESTENOSIS
Immunosuppressive drugs
Sirolimus (rapamycin)
Everolimus
ABT-578 (zotarolimus)
FK506 (tacrolimus)
Biolimus
Mycophenolic acid
Antiproliferative drugs
Paclitaxel
Angiopeptin
Tyrosine kinase inhibitor
Actinomycin D
C-myc antisense
Anti-inflammatory drugs
Corticosteroid
Tranilast
Antithrombosis agents
Heparin
Inhibitors of platelet aggregation
Extracellular matrix modulators
Batimastat
Prohealing agents
Endothelial coating
Antibodies to CD34
Nitric oxide donors
VEGF
17--Estradiol
FIGURE 21-5. Carriers for stent-based drug delivery. A: Polymeric-coated NIR stent
(Boston Scientific Corp. Natick, MA). A smooth coating of drug-releasing polymer has been
uniformly applied to the stent surface. B: Direct application of drug (paclitaxel) to a
ZilverPTX stent (Cook, Inc., Bloomington, IN).
Human experience with rapamycin-eluting stents in the noncoronary circulation is discussed

later in this chapter.
Paclitaxel-Eluting Stents
Paclitaxel, the active ingredient in the broad-spectrum chemotherapeutic agent Taxol (Bristol
Myers Squibb, New York, NY), is extracted from the bark and needles of the Pacific yew tree.
It is a microtubule stabilizer. Microtubules are intimately related to the functions of intracellular
transport, signaling, protein secretion, and motility. Paclitaxel disrupts these cellular processes
by forming stable dysfunctional microtubules. At cytostatic tissue concentrations, paclitaxel
inhibits neointimal hyperplasia in animal models (17). Several clinical trials of paclitaxel-eluting
stents in human coronary arteries have been conducted by Boston Scientific, Inc. (Natick, MA),
using a polymer-based delivery system (18,19), and by Cook Inc., assessing coronary stents
with the drug directly applied to the stent surface without polymer (20,21). The largest is
TAXUS IV, a multicenter U.S. trial, comparing treatment of de novo coronary lesions with
uncoated (652 patients) and polymer-based paclitaxel-coated Express stents (Boston
Scientific, Inc.; 662 patients) (22). In-stent restenosis at 9 months in the drug-coated group
was 5.5%, versus 24.4% in the noncoated stent arm, and in-segment restenosis was 26.6%
versus 7.9% (p <0.01).
There have been no completed trials assessing paclitaxel-coated stents in the noncoronary
circulation. A partially completed randomized prospective trial of paclitaxel-coated stents in the
superficial femoral artery (SFA) is discussed later in this chapter.
Zotorolimus-Eluting Stents
Zotarolimus, also called ABT-578, is a sirolimus analogue developed by Abbott
Pharmaceuticals (Abbott Park, IL) and being developed by two companies: Abbott Vascular
(Redwood City, CA), and Medtronic (Minneapolis, MN). Medtronic has actively pursued the
development of this agent through its ENDEAVOR series of trials (23,24), using the Endeavor
device, which consists of a cobalt chromium stent, zotarolimus, and a phosphorylcholine
polymer coating. The device was granted European approval in July 2005.
Abbott Vascular has also started clinical trials with the Zomaxx stent (Abbott Park, IL), which
comprises zotarolimus on a low-profile trilayer tantalum and stainless-steel stent (TriMaxx), with
an additional phosphorylcholine polymer coating (Pharmacoat; Biocompatibles International
Plc., Farnham, UK) for drug elution. Abbott Vascular's clinical trials are entitled Zomaxx I and II
(25).
Everolimus-Eluting Stents
The immunosuppressant everolimus is another sirolimus analogue. It has been tested in two
sets of trials: FUTURE, using everolimus-eluting stents coated with a bioabsorbable polymer
(26); and SPIRIT, assessing everolimus on a chromium-cobalt alloy stent with a durable
polymer as carrier (27). Guidant Corporation has been acquired by Boston Scientific and this
has created uncertainty about the future development of the everolimus-based stent.
DRUG-ELUTING STENTS IN PERIPHERAL VASCULAR

DISEASE
The degree to which a drug-eluting stent will impact the management of vascular disease in any
given region of the body is variable and specific to each clinical problem. In the coronary
circulation, surgical bypass to treat a blocked coronary artery involves the morbidity of a
thoracotomy and prolonged hospitalization including a stay in intensive care, so an endovascular
alternative does not have to be more durable to be an acceptable alternative. Clearly the
consequences of open surgery in peripheral vascular disease are not as dire. Drug-eluting
coronary stents profoundly decrease restenosis rates in comparison with bare metal stents,
and reducing the restenosis rate improves the clinical outcome (28). In most peripheral vascular
beds neither of these issues has been definitively proven. The clinical manifestations of
coronary artery disease are sufficiently common that the coronary artery is, by a considerable
margin, the most common site for endovascular stent insertion, thus companies can justify the
enormous expense of developing a coronary drug-eluting stent. In some peripheral vascular
disease states the number of patients is so low that a product designed to treat that entity
would not be commercially viable (e.g., mesenteric vascular ischemia).
The physical characteristics required of a stent or its coating varies considerably from one body
region to another. For instance, stents developed for the coronary circulation are
balloon expandable and typically vary from 2.25 to 4.0 mm in diameter and 0.8 to 2.0 cm in
length. They would not be appropriate for the relief of an occlusion in the SFA, where self-
expanding stents 5 to 7 mm in diameter and 4.0 to 8.0 cm in length are usually required.
The three most significant determinants of restenosis rates regardless of vascular bed are
vessel diameter, length of lesion, and diabetes (29). In addition, there are regional factors that
result in profound differences in restenosis rates between different segments of the peripheral
vasculature after endovascular intervention. These include repetitive deformation, burden of
calcification, and vessel wall composition and thickness relative to luminal diameter. The local
issues potentially influencing the performance of a drug-eluting stent in specific segments of the
peripheral vascular system and the relevant experience with drug-eluting stents are now
discussed.
FIGURE 21-6. Intracranial stent restenosis. A: Prestent angiogram demonstrating stenosis

of the right middle cerebral artery. B: Immediately post stent insertion no residual stenosis
is seen. C: Four months later there is a significant eccentric in-stent restenosis.
Intracranial Arteries
Clinical and Anatomic Considerations
More than 750,000 strokes occur annually in the United States, of which 8% to 10% are due to
intracranial atherosclerotic stenoses or occlusions (30). The placement of bare metal stents in
the intracranial circulation results in a restenosis rate of 32% at 1 year (Fig. 21-6) (31).
Intracranial arteries of similar
diameter to coronary arteries have much lower flow rates, making thrombosis more likely. The
arterial wall is thinner and there is incomplete or, intermittently, no adventitia, thus intracranial
arteries can easily be ruptured (32). As rupture is usually a catastrophic event, stents are often
deliberately undersized, however, in other arterial beds stent undersizing increases the
restenosis rate (29). Because of the thin vessel wall and incomplete adventitia, both drug
distribution and the restenosis cascade could potentially differ from those in the extracranial
circulation, thus different drug concentrations or length of delivery might be required.
Unfortunately there are no animal models appropriate for assessment of intracranial
endovascular interventions.
FIGURE 21-7. Drug-eluting basilar artery stent. A: Tight focal basilar artery stenosis. B:
After paclitaxe-leluting Taxus coronary stent (Boston Scientific Corp), the stenosis is
eradicated.
Experience with Drug-Eluting Stents

There have been no controlled trials of drug-eluting intracranial stents thus far. Observations
from small, nonrandomized, single-center experiences using drug-eluting stents designed for the
coronary artery (Fig. 21-7) have been reported. The Cleveland Clinic described their experience
in eight patients with intracranial artery stenoses who were successfully treated with four
sirolimus-coated Cypher (Cordis Corp, Miami, FL) and four paclitaxel-coated Taxus (Boston
Scientific Inc.) stents (33). One patient had an intraprocedural retinal embolism, but there were
no other complications. At a mean follow-up of 11.1 4.9 months (range, 2 to 17.3 months),
none of the patients had clinical or significant angiographic restenosis or required target vessel
revascularization.
The Albany Medical Center reported on 19 patients who received drug-eluting stents for intra-
and extracranial atherosclerotic disease (34). There were 12 males and 7 females, aged
between 36 and 83 years old (mean, 65 years). Thirteen heparin-, three sirolimus-, and three
paclitaxel-coated stents were placed. The stents were placed without complication in the
intracranial internal carotid artery in five patients, intracranial vertebral arteries in two patients,
midbasilar in three patients, vertebral artery origin in six patients, and middle cerebral artery in
three patients. There was one case of restenosis associated with recurrent symptoms, which
was treated with repeat drug-eluting stent placement. No other patients developed new or
recurrent neurological symptoms during the 2-year period of observation.
Carotid Arteries
Endovascular treatment of carotid stenosis with stenting (Fig. 21-8) has become an established
alternative to carotid endarterectomy (35). The Carotid Revascularization Using
Endarterectomy or Stenting Systems (CaRESS) phase I study was a multicenter, prospective,
nonrandomized trial comparing carotid stenting (CAS) with cerebral protection to carotid
endarterectomy (CEA) in patients with symptomatic and asymptomatic carotid stenosis (36). A
total of 397 patients (254 CEA and 143 CAS) were enrolled. There were no significant
differences in combined death/stroke rates at 1 year (13.6% CEA vs. 10.0% CAS) or
restenosis (3.6% CEA vs. 6.3% CAS). Based on this and other studies, the restenosis rates
have been felt to be extremely low for bare metal stents in the carotid artery in comparison with
the coronary circulation. However, the definition of restenosis used in carotid stent trials (80%
recurrent arterial narrowing if the patient is asymptomatic, 50% if symptomatic) differs from
that typically applied to coronary trials (50% recurrent narrowing irrespective of patient
symptoms). When selected subgroups of patients receiving carotid stents are analyzed or
criteria for recurrent stenosis other than 80% are applied, the stent restenosis rate is higher
than is generally perceived in the endovascular community. For example, when 55 patients in
whom recurrent narrowing occurring after carotid endarterectomy was treated by carotid stent
insertion were followed for a mean of 36 months post stent insertion, the cumulative rates of in-
stent restenosis-free survival at 1, 2, 3, and 4 years were 93%, 85%, 82%, and 76%,
respectively (37). Although a safe drug-eluting carotid stent potentially represents a common
application, the cost of evaluating the potential effects of eluted drug or potential dislodged
polymeric coating that might be distributed throughout the carotid circulation may be prohibitive.
Both would likely be nearly undetectable, but their assessment is certain to be mandated by
regulatory agencies.

To date there have been no reports of drug-eluting stents in the extracranial carotid artery. All
commercially available drug-eluting stents are balloon expandable, and self-expanding stents
only are used in the carotid artery. A single preclinical trial of sirolimus eluting self-expanding
stents in the carotid arteries of swine demonstrated a reduction of neointimal thickening in
comparison with noncoated stents (38).
Renal Arteries
The renal arteries have extremely high flow rates, approximately 20% of the cardiac output
flows through the paired arteries. Atherosclerotic renal artery stenosis most commonly
occurs at the origin of the artery, including the portion that passes through the aortic wall, thus
the plaque burden can be much larger than for other arteries of similar size (Fig. 21-9). The
high intraluminal flow rates and large mural area could potentially affect the drug distribution
delivered from a stent in comparison to other arteries with a similar luminal diameter.
FIGURE 21-8. Restenosis of internal carotid artery stent. A: Preprocedure angiogram

demonstrating a tight stenosis of the proximal internal carotid artery. B: A self-expanding
stent is appropriately positioned extending from the common carotid artery into the internal
carotid. C: Three months later there is marked in-stent restenosis.
FIGURE 21-9. Component of aortic atheroma in renal artery stenosis. Aortogram before
stent insertion demonstrates a focal stenosis (vertical arrow) at the origin of the left renal
artery. The aorta below the renal artery is narrowed (transverse arrow), inferring
thickening of the wall by plaque. Lipophilic drugs, in particular, might be distributed through
a larger plaque volume after release from a stent.
Renal artery stenosis occurs in 1% to 5% of hypertensive patients and is a significant cause for
renal failure, especially when occurring bilaterally or in a solitary kidney (39). Even though it is a
common entity, there is no clear consensus on diagnosis or therapy of atherosclerotic renal
artery stenosis, including a lack of prospective studies indicating any clinical benefit of
endovascular renal artery revascularization (40). The clinical aims of renal artery stenting are
generally stated to be prevention of further deterioration of renal function and resolution of, or a
decrease in, number of medications taken for hypertension. Reviews of the literature on renal
artery stenting report restenosis rates of between 9% and 25% at follow-up times ranging from
5 to 12 months (Fig. 21-10) (41).
One of only two published controlled multicenter trials of drugeluting stents in the noncoronary
circulation is the GREAT (Palmaz Genesis Peripheral Stainless Steel Balloon Expandable Stent
in Renal Artery Treatment) trial (42,43). The trial prospectively randomized 52 patients to
receive uncoated, bare metal, balloon-expandable Palmaz Genesis stents and 53 patients were
treated with sirolimus-coated Genesis stents (Cordis Endovascular) as treatment for renal
artery stenosis.
All stents were 5 or 6 mm in diameter. A sirolimus-eluting stent 15 mm long was coated with
210 g of sirolimus; a stent 18 mm long, with 256 g. Ninety percent of the sirolimus was
eluted within the first 30 days. The polymer and topcoat were the same as used for sirolimus-
eluting coronary stents.
When patients were re-examined 6 months posttreatment there was a reduction of restenosis
(defined as 50% narrowing within the stent) from 14.3% in the bare metal stents to 6.7% in
the sirolimus-coated group, although this did not reach statistical significance, likely due to the
small sample size (p = 0.30). However, five of the patients receiving a drug-eluting stent had
worsening of their renal function, compared with two in the bare metal group. This may have
been compounded by the fact that pretreatment renal function was worse in the sirolimus
patients (mean creatinine, 1.54 mg/dL) than the bare metal group (mean creatinine, 1.22
mg/dL). In addition, there
was no significant difference between the two groups regarding improvement in blood pressure
control or number of antihypertensive medications the patients had to take 6 months after stent
insertion.
FIGURE 21-10. In-stent restenosis left renal artery. A: Preprocedure angiogram
demonstrating a focal stenosis in the proximal left renal artery. B: Aortogram immediately
post stent insertion demonstrating slight underexpansion of the stent but otherwise
excellent positioning. C: Aortic injection 8 months poststent insertion revealing significant
luminal narrowing within the stent.
Thus even though drug-eluting stents resulted in a mild reduction in restenosis rate, in the short
term this difference did not result in improved clinical efficacy, and there may be an increase in
complications from using a drug-eluting stent. However, the study was not powered to account
for other variables that might influence clinical outcomes and the study is incomplete (the
patients will be followed for 2 years). There are no other clinical trials evaluating drug-eluting
stents in the renal arteries under way at this time, but at least two companies have conducted
preclinical testing with the intent to initiate human trials in the future.
Iliac Artery
Although the iliac arteries are a frequent site of stent insertion, the results of endoluminal
intervention are generally considered to be excellent. There have been no reports on the use of
drugeluting stents in the iliac artery at this time.
Superficial Femoral and Popliteal Arteries

The most extensive efforts in peripheral drug-eluting stents to date have been directed at the
SFA and popliteal arteries. In comparison with endovascular procedures in other peripheral
arteries of similar size, interventional techniques for treating the SFA-popliteal artery segment
have poor long-term patency rates. The TransAtlantic Inter-Society Consensus Group (TASC)
reviewed all published results for femoropopliteal interventions in patients with intermittent
claudication (44). After generating weighted averages of reported outcomes from the literature,
they reported 1-year primary patencies of 61% for angioplasty and 67% for stenting. Newer-
generation Nitinol self-expanding stents reduce the short-term restenosis rate but studies with a
longer follow-up are required (45,46).
It would be surprising if the superb results using drugeluting stents in the coronary circulation
could be achieved in the femoropopliteal segment by simply applying the same technology.
Earlier in this chapter three factors were mentioned as the most significant determinants of
restenosis rates regardless of vascular bed: diabetes, vessel diameter, and length of lesion. In
the femoropopliteal segment the latter two are very different than in the coronary circulation.
Diseased segments can be as long as 30 cm and the plaques are large and calcified, thus the
burden of atherosclerotic disease is enormously greater and of different composition in the SFA
compared with the coronary artery.
Perhaps most significantly, the femoral artery differs from other arterial beds in that it is
recurrently deformed in multiple directions with leg movement (47). This deformation consists
not just of flexion at the knee, but also of compression within the adductor hiatus and rotation
and longitudinal compression (Fig. 21-11). The artery is fixed at the groin and knee and mobile
in between, so the elastic vessel of a young person accommodates these forces well (48).
Atherosclerosis is characterized by circumferentially and longitudinally uneven loss of elastin
and deposition of calcium within the vessel wall, so when an
older, atherosclerotic patient bends his or her leg the effects of these forces are exaggerated,
even to the point of abrupt kinking. Not only can these recurrent external deformations in
themselves serve as recurrent stimuli to the restenosis cascade (49), but also they present
continual stresses on an endoluminal stent, potentially resulting in stent fracture (50). When
designing a drug-eluting stent for prevention of restenosis in the femoropopliteal segment, the
burden of disease and recurrent mechanical distortions significantly impact stent design as well
as choice of drug, dosage, and length of administration.
FIGURE 21-11. External mechanical forces exerted on the SFA-popliteal arterial segment
(also see Fig. 19-1 through Fig. 19-5).

The first published randomized trial evaluating drug-eluting stents in the noncoronary circulation
is the SIROCCO trial (SIROlimus Coated Cordis Smart Stents for the Treatment of Obstructive
SFA Disease) (51,52). In Phase I of the trial, patients with atherosclerotic blockage of the SFA
(TASC classification A, B, or C) were prospectively randomized into groups of 18 patients
receiving uncoated Nitinol self-expanding stents (SMART stents; Cordis Endovascular) or stents
coated with either a slow-release (>28 days) elution or fast-release (<15 days) polymeric
formulation of sirolimus. The sirolimuseluting stent coating had a thickness of ~5 m and was
composed of a proprietary elastic copolymer combined with sirolimus at a 30:70
drug:copolymer weight ratio. The amount of drug per vessel area was equivalent to that used in
coronary studies (90 g/cm2). All stents were 80 mm long. The mean number of stents
implanted per patient was 2.2. One important difference between the treatment groups was
that 100% of the lesions in the sirolimus-eluting stent patients had moderate to severe
calcification, compared with 46.7% of lesions in the uncoated stent patients (p = 0.002). Thus
patients who received sirolimus-eluting stents were generally at greater risk of restenosis than
the control group, and the distribution of released drug within the vessel wall could potentially
have been different.
FIGURE 21-12. Superficial femoral artery stents. A: SFA arteriogram 6 months post
insertion of a SMART stent demonstrating diffuse luminal narrowing due to neointimal
hyperplasia. B: Sirolimus-coated SMART stent 6 months postinsertion. There is minimal
intimal hyperplasia.
At 6 months, 17.6% of 17 patients in the uncoated group demonstrated in-stent restenosis (Fig.
21-12A), compared with 0 of 13 in the rapamycin group (Fig. 21-12B) (although an impressive
difference, this was not statistically significant due to sample size). At 18 months, of 17 patients
in the uncoated group, 4 (23.5%) had >50% in-stent restenosis, and in 1 patient (5.9%) the
stent had occluded. In the arm receiving drug-coated stents, 16 returned for follow-up; 3 of 11
(27.2%) who had received rapamycin in a fast-release coating had in-stent restenosis,
compared to 0 of 5 who had stents coated with rapamycin in a slow-release formulation.
Because of the apparently improved outcome in patients who had been treated with slow-
release rapamycin coating, the protocol was modified and a second phase performed.
The second phase of the SIROCCO trial (called SIROCCO II) was a multicenter, double-blind,
prospectively randomized
trial in which 57 patients were enrolled. Twenty-nine patients received SMART stents coated
with the same slow-release polymer/rapamycin formulation as in phase I, and 28 patients in the
control group received uncoated stents. The data were pooled, combining the slow-eluting stent
groups and control groups in phases I and II. At 6 months, the data looked encouraging, with a
0.38-mm late loss (a measure of ingrowth of tissue into the stent) and 0% binary in-stent
restenosis for the drug-eluting arm and 0.82-mm late loss and 11.6% binary instent restenosis
for the control arm. However, the reduction of restenosis from the drug coating was lost by 18
months; 20.9% of patients in the drug-eluting group and 17.3 % in the control group had
developed restenosis.
In phase I of the SIROCCO trial 31% of patients re-examined at 18 months were found to have
fractured stents. Although none of the fractures has had clinical consequences, this has raised
considerable concern with regulatory agencies. A drug-eluting stent for treatment of SFA
disease has not been commercialized to date.
A second study of drug-eluting stents in the femoral artery is under way. The Zilver PTX study
is a multicenter prospectively randomized trial comparing uncoated Nitinol self-expanding stents
(Zilver stent; Cook Inc.) to stents coated with paclitaxel applied without a polymer, in patients
with atherosclerotic stenosis or occlusion of the SFA (53). The total dose of paclitaxel and drug
elution rate has not been disclosed. At the time of writing, the study is partially enrolled and no
data are available.
Drug delivery from a coated conventional angioplasty balloon is an interesting alternative that
may allow local drug administration to the arterial wall at the time of angioplasty while avoiding
the issue of stent fracture. Scheller and colleagues found that a conventional angioplasty
balloon could be coated with paclitaxel and used to prevent stent-induced neointimal
hyperplasia in porcine coronary arteries merely by inflating the balloon in the artery for 1 minute
(54). The balloons were coated with paclitaxel by two different procedures. One method used
ethyl acetate as the solvent and resulted in approximately 2 g of paclitaxel per mm2 of balloon
surface; the second, using acetone, was completed with two concentrations of paclitaxel,
resulting in surface concentrations of 1.3 and 2.5 g per mm2. The coating resulted in a very
slight increase in profile but no recognizable change in flexibility. A dose-dependent inhibition of
in-stent restenosis with a reduction in neointimal area up to 63% was recorded. A prospective
randomized human trial applying this technique in the femoropopliteal segment was conducted
by Tepe (55). Unpublished interim 6-month results demonstrated a statistically significant
reduction in late lumen loss and target vessel revascularization in comparison with conventional
angioplasty performed with uncoated balloons.
FIGURE 21-13. Drug-eluting stent in the tibial artery. A: Preprocedure angiogram
demonstrating a tight stenosis narrowing the proximal 2 cm of the anterior tibial artery. B:
Immediately post insertion of a paclitaxel-coated Taxus stent there is no residual stenosis.
C: At 7 months, appearances are virtually unchanged. (Images courtesy of Peter Bromley,
M.D.)
Tibial Arteries
Severe disease of the tibial vessels is typically associated with systemic diseases such as
diabetes or renal dysfunction, which will affect the outcome of any treatment. The literature on
tibial endovascular intervention typically reflects better outcomes than the general pessimism of
most interventionists regarding these procedures (56). As in the intracranial circulation,
improvement in devices and adjunctive antiplatelet therapy has resulted in an increased number
of procedures being performed. Although the tibial vessels are of similar size to coronary
arteries, lesion lengths are much longer, so a relatively small proportion of patients presenting
with tibial artery blockage can be treated with drug-eluting stents designed for the coronary
artery (Fig. 21-13). On a theoretical basis the distribution of
drug in the arterial wall would differ from that in the coronary circulation because flow rates are
lower and there is a higher frequency of severe calcification. The tibial arteries are not subject
to the marked mechanical forces of the femoropopliteal segment but balloon-expandable stents
can be crushed if the calf is subjected to compressive forces.

The only published human experience with drug-eluting stents in the tibial arteries is a
description of the 6-month angiographic results from a prospective single-center study
investigating the efficacy and outcome of commercially available sirolimus-eluting coronary
stents (Cordis Endovascular) used as bailout after unsatisfactory balloon angioplasty in patients
with critical limb ischemia (57). Sixty-five lesions in 40 infrapopliteal arteries were treated in 29
patients with bare metal stents (38 stenoses and 27 occlusions). Another 29 patients were
treated with sirolimus-eluting stents in 66 lesions (46 stenoses and 20 occlusions) in 41 vessels.
Six-month primary patency was 68.1% in the bare metal group, versus 92.0% in patients
treated with sirolimus-eluting stents (p <0.002). Binary in-stent and in-segment restenosis rates
were 55.3% and 66.0%, respectively, in patients with bare stents, versus 4.0% and 32.0% in
patients treated with sirolimus-eluting stents (both p's <0.001). The target lesion reintervention
rate at 6 months was 17.0 % versus 4.0% (p = 0.02). Limb salvage was reported as 100% in
both groups. Further, prospectively randomized studies will be required to assess whether
these superb results can be achieved consistently.
Patients with tibial artery stenoses frequently have comorbidities in addition to a significant
burden of atheroma, as illustrated in the BELOW study (58). In that study, patients with
ischemic ulcers due to tibial artery disease were randomly assigned to one of four treatment
groups: parenteral abciximab and a sirolimus-coated stent, abciximab and a bare stent,
abciximab and angioplasty, and angioplasty alone. At 6 months, of the first 14 patients
randomized to the drug-eluting stent arm, 1 patient had died, in 1 patient the treated limb had
been amputated, and 3 patients were lost to follow-up. Eight patients had patent stents (one
with approximately 30% narrowing) and one was patent but with >50% restenosis. The
outcomes of patients in the other treatment arms is not available at this time, however, this
study may provide some insight into the relative benefits of improvements in endovascular
implants and adjunctive pharmaceuticals.
CONCLUSION
Considerable further research is necessary before the ultimate role of drug-eluting stents in
peripheral vascular disease can be defined. It is clear that the remarkable success of drug-
coated balloon-expandable stents in midsized coronary arteries cannot be repeated by merely
applying the same drugs using the same dose and delivery methods as in other arterial beds.
Multiple lessons have already been learned. The SIROCCO trial taught us that the same
profound inhibition of intimal hyperplasia can be achieved as in coronary arteries at 6 months,
but a durable effect is quickly lost because of the very different milieu of the SFA. In the
GREAT trial we saw that while a reduction of restenosis was achieved (albeit less marked than
in other drug-eluting stent trials), this did not confer a significant clinical benefit to the patient.
And finally, but perhaps most importantly, for the first time in the medical device industry we
have a technology that is so expensive to develop and test that even if efficacy can be
demonstrated in preclinical testing, economics may prevent many applications from becoming
clinical reality.
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> Table of Contents > Section III - Vascular Interventions > Part B: - Systemic Venous Interventions > Chapter 22 - Interventional
Management of Deep Vein Thrombosis
Chapter 22
Interventional Management of Deep Vein Thrombosis
Mahmood Razavi
LOWER EXTREMITY DEEP VEIN THROMBOSIS

Deep vein thrombosis (DVT) is the third most common cardiovascular disease in the United
States, with an annual incidence of between 56 and 182 per 100,000 patients (1, 2, 3). The
major risk factors for DVT include surgery, trauma, immobility, obesity, cancer, various
thrombophilic conditions, and a history of DVT. The most serious complication of DVT is
pulmonary embolism (PE), which carries a mortality risk of between 7.5% and 17% (4). It is
estimated that 40% to 50% of patients with proximal DVT will suffer from silent PE (5). DVT
and PE are thus part of a spectrum of a clinical entity commonly referred to as venous
thromboembolism (VTE).
Another potentially serious complication of DVT is the debilitating condition known
postthrombotic syndrome (PTS), which consists of limb pain, edema, stasis dermatitis, and
ulcers. PTS develops in approximately 25% to 60% of patients with DVT, depending on the
level and extent of thrombus (6,7). The main pathophysiologic mechanism of PTS is ambulatory
venous hypertension precipitated by venous valvular reflux and outflow obstruction. Despite the
grim statistics on PTS, the focus of therapy in the great majority of patients with DVT remains
anticoagulation. In a prospective registry of 5,451 patients with confirmed DVT, only 1%
underwent attempted removal of clot by thrombolysis (8). This lack of attention to the status
and function of the limb after DVT is mainly due to the paucity of Level I data on preventive
therapies for PTS.
Rationale for Interventional Therapy

There are three major objectives for the interventional management of DVT: (a) to reduce the
risks of PE and recurrent DVT, (b) to prevent PTS by restoration of venous patency and
preservation of valvular function, and (c) to provide immediate symptom resolution. As
mentioned above, however, the standard of care has not changed for decades and remains
anticoagulation with supportive measures. Three major problems exists with the current
management strategy of anticoagulation alone (9): (1) it is ineffective in actively removing acute
thrombus; (2) treatment algorithms are based solely on the presence or absence of thrombus,
without consideration of the extent and location of the involved venous segments; and (3)
treatment of an underlying anatomic abnormality within the vein is underappreciated.
It is important to keep in mind that neither unfractionated heparin, low molecular weight heparin,
nor warfarin can break down thrombus. Restoration of patency of the vein is dependent on the
endogenous fibrinolytic activity of the venous segment. Spontaneous complete clearing of
iliofemoral segments seldom, if ever, occurs when treated with anticoagulants alone. Of all
comers, only 10% of patients will have spontaneous lysis of their DVT within 10 days of heparin
therapy and up to 40% of patients will continue to have propagation of thrombus despite
anticoagulation (10,11). These factors contribute to the increased risk of recurrent DVT and
PTS in these patients.
Although currently no Level I scientific data exist quantifying the actual superiority of adjunctive
use of interventional approaches to anticoagulation alone, there is evidence supporting the
benefits of early removal of clots. In a prospective multicenter registry of patients with DVT
who underwent thrombolysis, Mewissen and colleagues reported venous patency in the
majority of patients who had successful lysis 1 year after therapy (12). Elsharawy and Elzayat,
in a small, randomized study, observed that dissolving the clot significantly reduced valvular
reflux and improved venous patencycountering the two main pathophysiologic mechanisms of
PTS (13). In another study, Comerota et al. found significant improvements in the health-related
quality of life in those who had been treated with adjunctive catheter-directed thrombolysis
(CDT) versus anticoagulation alone 16 months after treatment (14).
Based on these and other observational studies in the literature, an interventional approach to
patients with DVT may be warranted.
Patient Selection
As minimally invasive therapies for the interventional treatment of DVT evolve, the indications
and criteria for patient selection also change, involving an increasing number of patients with
both acute and chronic DVT. The currently accepted criteria for the optimal candidate for
interventional therapy are as follows.
1. Presence of symptomatic proximal DVT: This refers to complete or partial thrombosis of any
vein above the popliteal level. The highest risk of PTS and possibly PE exists in patients with
thrombosis of common femoral and/or iliac veins. Due to the higher risk of recurrent VTE and
PTS in this subset of patients, a more aggressive approach is warranted.
2. Acute thrombosis: Although the best results are obtained in patients with acute (<14 days)
first-episode DVT, a substantial reduction in the magnitude of symptoms can be observed
after endovascular thrombolysis and recanalization of occluded central veins with subacute
and chronic thrombosis. There are currently no effective endovascular therapies for
chronically diseased femoropopliteal venous segments.
3. Reasonable life expectancy: Keeping the objectives of therapy in mind, those who would
most benefit from interventional clot management are those with a reasonable life
expectancy. Prevention of PTS may not be a high priority in patients with advanced age or
late-stage malignancy. The only indication for aggressive treatment of DVT in such patients is
a limb-threatening condition such as phlegmasia cerulea dolens.
4. Absence of contraindications to thrombolysis and anticoagulation: Table 22-1 lists the
generally accepted criteria for contraindications to thrombolysis. It should be noted that due
to the continuing evolution of more effective percutaneous mechanical thrombectomy devices,
many patients with contraindications to pharmacologic thrombolysis could still be treated with
these devices, with or without small doses of lytic agents.
TABLE 22-1 COMMONLY ACCEPTED CONTRAINDICATIONS TO

THROMBOLYTIC THERAPY
Absolute contraindication Relative contraindication
1. Active or recent (<3 months) internal bleeding

2. History of recent stroke
1. Recent (within 10 days) major
3. History of intracranial or intraspinal tumor,
surgery, trauma, or CPR
vascular malformation, or aneurysm
2. Uncontrolled hypertension
4. Recent craniotomy or spinal surgery
3. Bacterial endocarditis
5. Pregnancy
4. Diabetic retinopathy
6. Coagulopathy
7. Severe liver dysfunction
Technique
The approach to the interventional management of DVT can be quite varied and no one
technique has been shown to be superior. In general, however, the initial venous access should
be in the direction of flow. A low popliteal or tibial access is typically obtained using ultrasound
guidance. Color flow, compressibility, and size criteria can be used to distinguish artery from
vein. In the case of a thrombosed popliteal vein, an enlarged tubular structure with no color or
Doppler signal is usually characteristic of the vein and can be accessed. Most practitioners use
a small initial access such as a 4- or 5-Fr sheath and upsize as necessary. Attempts should be
made to cross the occluded segments initially and determine the extent of
thrombosis/occlusion. The hydrophilic wire/catheter combination is most commonly used to
accomplish this. Occasionally it is not possible to cross the entire length of the occlusion due to
the acute-on-chronic nature of some DVT patients. In such patients crossing can usually be
accomplished after an initial trial of thrombolysis.
Once the extent of thrombosis is determined, one of several strategies can be employed.
Percutaneous mechanical thrombectomy (PMT) can be used to debulk the clot before
pharmacologic lysis or to clean up isolated remaining thrombi after lysis. Occasionally PMT
alone or in combination with low doses of lytics is sufficient to establish antegrade flow (see
Combination Therapy, below). More frequently, however, PMT alone using the current
generation of devices is insufficient to clear the clot and is followed by infusion of thrombolytic
agents.
Although infusion of fibrinolytics through end-hole catheters can be successful in arterial lysis, it
tends to be less effective in patients with DVT. The recommended method is to use multi-side-
hole catheters spanning the length of the thrombosis.
Prophylactic use of inferior vena cava (IVC) filtration is rarely needed in these patients during
interventional therapy. Placement of optional filters is recommended, however, in cases of
partially adherent or floating large clots in central veins.
Thrombolytic Agents
The currently available thrombolytic agents are plasminogen activators. As such, they indirectly
cause lysis of fibrin by converting plasminogen into plasmin. The generated plasmin then
cleaves the fibrin strands in the clot. This process is mainly regulated at two levels. The first
involves plasminogen activator inhibitors (PAI). The most important of this class of inhibitors is
PAI-1. PAI-1 levels have been shown to be elevated in patients with DVT, possibly prolonging
the lytic process (15,16). Tenecteplase (TNK) is more resistant to PAI-1 and may thus be the
preferred agent. It should be noted, however, that despite this theoretical advantage, TNK's
superiority to tissue plasminogen activator (t-PA), reteplase (r-PA), or urokinase (UK) has not
been establish clinically in these patients. Other promising agents such as Plasmin and
Alfimeprase are direct fibrinolytic agents with potential safety and efficacy advantages. They
are currently not available for clinical use in the United States and no clinical data on their use in
DVT exist.
Infusion Protocol
Constant dose infusion through multi-side-hole catheters is the most commonly used protocol.
Although many practitioners give a bolus of thrombolytic drugs, there are no convincing data
that this practice is either more effective or more dangerous than constant dose infusion for this
application. Table 22-2 lists the suggested doses for these agents.
Combination Therapy
As mentioned above, occasionally PMT, alone or in combination with low doses of lytics, is
sufficient to establish antegrade flow. Table 22-3 lists the currently available PMT devices. A
commonly used technique is the combination of a rheolytic device such as the AngioJet (Possis
Medical Inc.) with a thrombolytic agent such as UK or t-PA. This technique is commonly
referred to as power pulse and is used variably for DVT. One common method is to mix 10 to
20 mg of t-PA or 500,000 to 1 million U of UK with 50 mL of normal saline and use the mixture
as the injector solution of the AngioJet. The effluent lumen (outflow channel) of the device is
closed using a three-way stopcock and the length of the clot is pulsed by turning
the AngioJet on and force-injecting the diluted lytic solution into the clot. After a period of 20 to
30 minutes the outflow switch is opened and the device is used in the traditional fashion
throughout the clot.
TABLE 22-2 MOST COMMONLY USED DOSES FOR CURRENTLY

AVAILABLE AGENTS DURING VENOUS THROMBOLYSIS
Agent Infusion dose
Urokinase (UK) 60,000-120,000 U/hour
Alteplase (t-PA) 0.5-1.0 mg/hour
Reteplase (r-PA) 0.5-1.0 U/hour
Tenecteplase (TNK) 0.25-0.5 mg/hour
TABLE 22-3 CURRENTLY AVAILABLE PERCUTANEOUS MECHANICAL

THROMBECTOMY DEVICES. ALTHOUGH MOST OF THESE DEVICES
HAVE BEEN USED TO TREAT DVT, AVAILABLE PEER-REVIEWED DATA
ARE VERY SCANTY.
Manufacturer Device(s)
Arrow International Arrow-Trerotola PTD
Bacchus Vascular Trellis-8 infusion system
Boston Scientific Oasis thrombectomy system
Cordis Endovascular Hydrolyser
Datascope Prolumen
EKOS Corporation Lysus Infusion System
ev3 X-Sizer, Helix Clot Buster
IDev Technologies, Inc. AKonya Eliminator
Kerberos Proximal Solutions Rinspiration System

Kensey Nash Corporation ThromCat Thrombectomy System
OmniSonics Medical Technologies Resolution Endovascular System
Possis Medical AngioJet (Xpeedior, DVX, AVX, XVG, XMI)
Straub Medical Rotarex, Aspirex
More recently, promising data presented in abstract form suggest that the Trellis-8 (Bacchus
Vascular Inc.) can be used in combination with low doses of lytic agents to clear the clot and
reestablish flow in a single session in the majority of patients (17). This obviates the need for
prolonged infusion of thrombolytic agents and monitoring in the intensive care unit, potentially
enhancing the safety of thrombolytic therapy. This has been referred to as isolated
fragmenolysis.
The Trellis-8 catheter is a pharmacomechanical device that consists of proximal and distal
occlusion balloons, separate infusion and aspiration ports between the balloons, and a powered
oscillation drive unit attached to a sinusoidal wire that produces oscillations in the catheter.
After placing the device in the desired segment of the vein, balloons are inflated to isolate the
venous segment. Four to ten milligrams of t-PA (2 to 5 mg of TNK or 4 to 10 U of r-PA) is then
injected through the infusion port, and the device turned on. The speed and amplitude of the
generated oscillations are adjusted and the device is allowed to operate for a period of 15 to
30 minutes. The remaining drug and clot can then be aspirated through the aspiration port. The
balloons are then deflated and a venogram is performed (Fig. 22-1). This can be repeated if
necessary until flow is established.
Other forms of combination therapy focus on achieving a more complete clearing of the clot
during thrombolysis. An example of such includes the use of sonic waves during CDT.
Preliminary data on ultrasound-accelerated CDT using the EKOS Lysus System (Bothell, WA),
presented in abstract form, suggest that the efficacy of lysis may be improved in both acute
and acute-on-chronic DVT (18).
Interventional Algorithm
Figure 22-2 depicts the suggested algorithm for interventional management of patients with
acute DVT (19). The objective is to establish unobstructed flow from the affected extremity to
the heart when possible. After removal of acute thrombus by either CDT or combination
therapy, any obstruction to flow should be treated by adjunctive angioplasty and stent
placement (Fig. 22-3). A common anatomic impediment to flow encountered after clearance of
clot is iliac vein compression syndrome (May-Thurner syndrome). This is caused by the
overriding right iliac artery compressing the underlying vein and leading to stasis of flow. The
most common affected vein is the left common iliac vein. Other less frequently affected
locations include the left external iliac vein, IVC just above the confluence of the iliac veins (Fig.
22-4), and the right common iliac vein.
Use of metallic stents has been associated with a good outcome in central veins such as the
IVC and iliac veins (20,21). Stenoses caused by residual chronic clot or synechia caused by
May-Thurner syndrome are hence treated by placement of appropriately sized stents. In the
iliac veins we usually use stents between 10 and 16 mm in diameter, with 12 to 14 mm being
the most commonly used. Post-stent implantation angioplasty is frequently required and should
be gauged to the patient's pain during balloon inflation. Angioplasty with oversized balloons
increases the risk of venous rupture. At the same time, use of smaller stents and balloons
predisposes to early restenosis/rethrombosis. Appropriate sizing of both stents and balloons is
thus paramount for a good outcome.
Experience with the current generation of metallic stents in the femoral veins below the
saphenofemoral junction has been largely disappointing (12) and hence is not recommended.
Angioplasty of the femoral vein can occasionally aid in establishing better flow through a
stenotic or partially thrombosed segment. Stenoses due to chronic organized clot or fibrosis
rarely respond to angioplasty alone and are usually left alone without stenting below the
saphenofemoral junction for reasons mentioned above.
Adjunctive Pharmacotherapy
Many patients with DVT suffer from one or more of a variety of thrombophilic conditions.
Furthermore, slow flow predisposes these patients to pericatheter thrombosis during the
procedure. For these reasons we fully anticoagulate our patients with systemic heparin during
interventions. As with any interventional or thrombolytic infusion procedure, adequate
medication for pain and back discomfort should be prescribed on an as-needed basis.
A beneficial role of antiplatelet therapies in these patients, if any, is unproved.
Results
The largest DVT thrombolytic database to date is the venous registry (12). This was a
prospective registry of patients with DVT who underwent catheter-directed thrombolysis with
UK. The exclusion criteria included isolated calf DVT, thrombosis after primary thrombectomy,
and contraindications to lysis, anticoagulation, or angiography. The method of thrombolysis was
left to the treating physician. Of 473 patients enrolled in the study, 287 (303 limbs) completed
the follow-up at 1 year. Seventeen percent of the patients had <50% lysis and were considered
failures of thrombolytic therapy. Figure 22-5 depicts the 1-year patency curves for all patients,
including those with chronic and acute-on-chronic symptoms. In this study a strong relationship
between early thrombus removal and 1-year patency was established. Analysis of subgroups
revealed 96% patency in patients with acute iliofemoral DVT who had no history of DVT and
had complete lysis. This emphasizes the importance of treating such patients at first
presentation if they have no contraindications to intervention. The complications
in this study included pulmonary embolus (1.3%) and bleeding (11%), with one fatal intracranial
hemorrhage (0.2%).
Large-scale studies using lytic agents other than UK have not been conducted to date but
smaller retrospective reports have shown promising results. Vedantham et al. performed a
pooled analysis of 19 published peer-reviewed studies using CDT for acute DVT, which included
the results of the venous registry mentioned above (22). Anatomic clot clearance was evaluated
in 860 limbs and success was achieved in 88% (range, 76%-100%) of patients. Similar to the
venous registry data reported above, success was higher in patients with acute DVT (92%).
FIGURE 22-1. A: Ascending prone venogram in a 74-year-old female who was 10 days
status post lumbar fixation shows extensive DVT of the left lower extremity. She had
initially undergone placement of an optional IVC filter at an outside institution due to
contraindications to anticoagulation 3 days prior to this venogram. The patient's
symptoms continued to worsen and she was transferred for interventional management of
her DVT. B: Filling defects in the left common femoral and iliac veins with stasis of flow. C:
After infusion of 5 mg of TNK, Trellis-8 local fragmenolysis was initiated. Image shows
oscillations of the sinusoidal wire. D: Thirty minutes after the initiation of isolated lysis
repeat venogram showed clearance of clot in the femoral vein. E: Residual narrowing and
clot in the iliac vein were stented to provide unobstructed outflow. The patient's symptoms
resolved completely 3 days after this procedure. F: Follow-up venogram in supine position
at the time of removal of the optional IVC filter 3 months later shows continued patency of
the veins.
There is a paucity of published results on PMT alone or in combination with lytic agents in the
peer-reviewed literature. Kasirajan et al. reported extraction of >90% of clots in 4 of 17
patients with DVT using the AngioJet alone (23). Additional CDT was performed in 9 of 17
patients. Significant improvement in symptoms was observed in 14 of 17 patients. Lee et al.
used the Arrow-Trerotola percutaneous thrombectomy device with or without low-dose UK in
the treatment of 25 patients with acute iliofemoral DVT (24). The overall 1-year clinical success
rate was 92% (23 of 25 patients). Valvular insufficiency occurred in two patients in their study.
Vedantham et al. used adjunctive PMT with the AngioJet after CDT in 20 patients (28 limbs),
with an 82% success rate (25). They also reported major bleeding in three patients (no
intracranial bleeds). The same group also published their results using CDT with reteplase and
adjunctive PMT with the Helix device (26). In the latter study, 23 limbs in 18 patients were
treated. Immediate success was achieved in 96% of the limbs, with one major bleed (6%). Late
(mean, 19.8 11.6 months) modified Venous Disability Scores were 0 (none) for 6 limbs, 1
(mild) for 10 limbs, 2 (moderate) for 3 limbs, and 3 (severe) for no limbs.
The results of a Trellis-8 study in 113 patients have been presented in abstract form. This was
a prospective voluntary collection of data from 48 sites by the manufacturer of the device (27).
Antegrade flow with removal of thrombus was reported in 80% of the patients in a single setting
without the need for CDT or intensive care unit monitoring. Adjunctive placement of stents was
done in 42 of the 113 patients. The
major weakness of the study was the absence of independent verification of the data by a core
laboratory.
FIGURE 22-2. Algorithm for interventional management of patients with lower extremity
DVT after initiation of thrombolysis. Anticoag, anticoagulation; SPJ, saphenofemoral
junction.
In an attempt to study the correlation of thrombolytic treatment with improvement in quality of

life (QOL), Comerota et al. administered a health-related QOL instrument to 68 patients who
had undergone CDT and compared it to the results for 30 patients treated with anticoagulation
alone (14). Results showed significant improvement in QOL in patients who had undergone
thrombolysis (Fig. 22-6).
Management of Patients After Interventional Therapy

After the completion of intervention, anticoagulation is withheld briefly to remove the access
sheath. Patients should be anticoagulated systemically approximately 1 to 3 hours after
removal of the sheath. Unfractionated heparin is used to achieve a partial thromboplastin time
of 1.5 to 2.5 times control to bridge the patients to the optimal International Normalized Ratio
(INR) using warfarin. Low molecular weight heparin can be substituted for unfractionated
heparin. The optimal INR and the desired duration of warfarin anticoagulation depend on the
etiology of DVT. The typical INR is between 2.5 and 3.0 and patients remain on an
anticoagulation regimen for 6 to 9 months.
Patients' symptoms typically subside 2 to 5 days after restoring flow. Those who do not
experience relief of symptoms should be investigated for early rethrombosis and possible
reintervention. Follow-up should include workup for thrombophilic conditions (typically in those
<50 years of age) and ultrasound of both lower extremities, which is usually done at 3, 6, and
12 months. Most vascular specialists recommend yearly follow-up thereafter for 3 to 5 years or
symptomatically as necessary.
Once patients are discharged, careful monitoring of their INR level should be performed and the
warfarin dose adjusted as necessary. Use of graduated compression stockings reduces the
risk of PTS and should be considered in all patients after endovascular clot removal (28).
UPPER EXTREMITY DEEP VEIN THROMBOSIS

Upper extremity DVT (UEDVT) is less common than lower extremity DVT, accounting for 4% to
11% of all cases of DVT (8,29,30). It is usually categorized into primary and secondary types,
which have distinct natural histories, treatment strategies, and clinical outcomes. UEDVT is
frequently asymptomatic. When symptomatic, it can include pain of the arm, hand, neck, and
shoulder, edema, heaviness, and tenderness. The complications of PE and PTS can also occur
in these patients, although they are less well characterized and understood. Pulmonary
embolization occurs in 5% to 10% of cases and is more common in patients with secondary,
versus primary, venous thrombosis. PTS is more common among patients with primary UEDVT
and occurs in 20% to 70% of affected individuals.
Risk factors for UEDVT include strenuous arm exercise in susceptible individuals, central
venous catheterization, inherited thrombophilic conditions, and acquired hypercoagulable states
such as pregnancy, oral contraceptive use, and cancer. As with DVT of the lower extremities,
any unexplained recurrent UEDVT should trigger an investigation of inherited or acquired
hypercoagulable states. In one study, one fourth of cases presenting with idiopathic UEDVT
were found to have a malignancy within a year of diagnosis (31).
The etiology of primary UEDVT is usually related to repetitive provocative movements of the
arm and is referred to as effort vein thrombosis or Paget-Schroetter syndrome. In this
condition, there is extrinsic compression of the subclavian veins at the thoracic outlet by
muscular/ligamentous structures (anterior scalene, subclavius) and bones (first rib and clavicle).
For this reason, the focus of interventional treatment of this entity should be clot removal. The
underlying anatomic narrowing of the vein does not respond to angioplasty or stenting and
should not be treated as such. Paget-Schroetter syndrome is more common among younger
individuals, with the majority of cases giving a history of recent repetitive upper extremity
movement (32).
Secondary UEDVT is more common than the primary variety and is due to indwelling venous
catheters, pacemaker wires, trauma, and compression by neoplasms. Frequently, multiple
predisposing factors coexist. The presence of catheters inserted through the subclavian vein is
associated with a higher rate of venous thrombosis than through the internal jugular veins. The
majority of catheter-related venous thromboses, however, are asymptomatic. In addition to the
possibility of PE and PTS, secondary UEDVT can be complicated by loss of venous access in a
population that most needs it.
Interventional Management of Upper Extremity Deep Vein

Thrombosis
The initial step is confirmation of thrombosis. Central vein stenoses or chronic occlusions may
be present without acute clot. In general, acute thromboses of veins below the axillary veins are
adequately treated with anticoagulation and supportive measures. Development of late
sequelae are uncommon in such patients. Endovascular approaches are reserved for the
presence of clot in veins more central to axillosubclavian segments.
FIGURE 22-3. Ascending venogram in the prone position in a 36-year-old female with a
history of inherited thrombophilia and a 7-day history of worsening left lower extremity
edema and pain. A, B: Filing defects representing thrombosis of femoropopliteal and
iliofemoral venous segments are present. C: After overnight infusion of thrombolytic agent,
clearing of the entire clot burden is accomplished. Compression of the left common iliac
vein representing May-Thurner syndrome is noted (arrow). D: The lesion is stented to
provide unobstructed outflow from the limb.
FIGURE 22-4. Uncommon location of May-Thurner syndrome. Postlysis inferior vena
cavagram (prone) in a patient with DVT shows the impression of the right common iliac
artery at the IVC confluence (arrow).
As mentioned above, PTS is a common sequela of primary venous thrombosis treated by

anticoagulation alone. Because of this, there has been a much faster adoption of CDT and
other endovascular clot removal techniques by both the medical community and the patients.
The technique of thrombolysis/thrombectomy is similar to that for lower extremity DVT and is
discussed above. Ultrasound-guided access into the basilic or brachial veins just above the
elbow is initially obtained. Venogram is performed to determine the extent of thrombosis. In
patients with effort vein thrombosis, the central extent is usually at the thoracic inlet where
venous compression occurs. Attempts are made to cross the thrombosed segment, and
thrombolysis with or without PMT is initiated. Use of adjunctive PMT has been associated with
faster thrombolysis in this territory (26). After clearance of clot in patients with Paget-
Schroetter syndrome, angioplasty or stenting of the narrowed thoracic inlet should not be
attempted since the narrowing is an extrinsic anatomic compression of the vein and does not
respond to the currently available endovascular techniques (33). Surgical decompression is the
usual next step but the timing remains controversial. Some vascular surgeons operate early
after thrombolytic therapy, while others advocate anticoagulation with delayed decompression.
FIGURE 22-5. One-year venous patency rates after thrombolysis in the Venous Registry
(12).
FIGURE 22-6. Results of an 80-item QOL survey in 98 patients with iliofemoral DVT: lysis
versus heparin. Improvement in QOL was statistically significant in all categories at 16
months posttreatment. (From Comerota AJ, Throm RC, Mathias SD, et al. Catheter-
directed thrombolysis for iliofemoral deep venous thrombosis improves health-related
quality of life. J Vasc Surg. 2000;32:130-137. Used with permission.)
The standard of care for symptomatic patients with secondary UEDVT consists of
anticoagulation, arm elevation and compression, and removal of the indwelling venous line if
present. Symptoms resolve in more than half of such patients but residual stenoses and chronic
occlusions may develop. Furthermore, removal of venous catheters leads to the loss of venous
access in patients with a continued need for it. If prompt symptom resolution is not achieved by
anticoagulation alone, the patient should be evaluated for thrombolytic therapy. Any existing
central vein catheters should not be removed prior to CDT. A venous access is obtained in the
low brachial or basilic veins just above the elbow, and clot removal attempted in a similar
fashion to that for primary UEDVT mentioned above. The cephalic vein is a less desirable
alternate access. Once the acute clot is cleared, any underlying stenoses can be treated by
angioplasty. Stents are reserved for brachiocephalic veins or superior vena cava. Stents in
peripheral veins have not had a good outcome. An offending subclavian catheter may then be
removed and placed in the internal jugular vein if possible. These patients should then receive
anticoagulation for 3 months, depending on the coexistence of other predisposing factors. As
with any other form of thrombolysis and/or anticoagulation, contraindications to such should be
excluded. Endovascular techniques have been highly successful in these patients, with the
ability to successfully remove the clot and salvage the central venous catheters in up to 87% of
cases.
SUMMARY
For the past several decades, anticoagulation has remained the cornerstone of therapy for
DVT. While it has reduced the incidence of and survival after PE, evidence is accumulating that
it may not be sufficient therapy for the other complication of DVT, namely, PTS. In other words,
anticoagulation may be sufficient for lungs but not for limbs. While the causes of lack of
attention to the prevention of PTS are multifactorial, broadening the use of CDT will require
well-designed, convincing randomized trials.
References
1. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the
hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism.
The Worcester DVT Study. Arch Intern Med. 1991;151:933-938.
2. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis
and pulmonary embolism: a 25-year population-based study. Arch Intern Med.
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> Table of Contents > Section III - Vascular Interventions > Part B: - Systemic Venous Interventions > Chapter 23 - Treatment
Options of Pulmonary Emboli
Chapter 23
Treatment Options of Pulmonary Emboli
Harneil Sidhu
Klaus Hagspiel
Venous thromboembolism (VTE) most frequently manifests as pulmonary embolism (PE), deep
venous thrombosis, or both. Despite difficulties in detection, multiple cohort studies have
demonstrated similar incidence estimates in different geographic areas. In a community-based
study in western France the overall incidence was 1.83 per 1,000 (1). In a 25-year prospective
study the incidence was estimated at 1.22 per 1,000 among adults in the United States (1). The
Longitudinal Investigation of Thromboembolism Etiology estimated an incidence of 1.45 per
1,000. Assuming, a conservative incidence of 1.5 per 1,000, the United States, with a
population of 300 million, has a recognized incident rate of approximately 450,000 cases per
year.
The relative incidence rate of PE has been highly dependent on the methodology of studies,
with most clinical studies reporting an approximate percentage of 28% to 41% (2,3). Autopsy
studies, on the other hand, have generally overestimated the relative incidence, likely due to the
presence of asymptomatic PE (2).
The rate of PE mortality remains high, although some controversy exists regarding whether the
rate is decreasing (5). In the International Cooperative Pulmonary Embolism Registry of 2,454
consecutive patients from 52 institutions in seven countries, the 3-month mortality rate was
17.4% (6). A similar mortality rate was indicated by the Prospective Investigation of Pulmonary
Embolism Diagnosis study, which found a case fatality rate of 15% within 3 months after PE
(7). In a Japanese registry of 533 patients with PE, the in-hospital mortality rate was 14.0%
(8). In fatal cases, the majority of deaths occur in the first 1 to 2 hours (9). Many additional
deaths occur each year as a result of undiagnosed massive PE that is mistaken for acute MI or
ventricular arrhythmia.
RISK FACTORS
Multiple risk factors for VTE have been identified (Table 23-1). VTE is rarely encountered
without the presence of an underlying risk factor. A review of 1,231 consecutive patients
treated for VTE identified one or more risk factors in 96% (10). All known risk factors are
based on the underlying pathophysiology described by Rudolph Virchow: vascular endothelial
damage, stasis of blood flow, and hypercoagulability.
Risk after major general surgery is well documented, with major surgery defined as requiring
>30 minutes of general anesthesia (11). Other types of major surgery shown to have increased
risk include coronary bypass surgery (12), major urological surgery (4), and neurosurgery (14).
Lower extremity and pelvic orthopedic operations, excepting arthroscopic knee evaluation (15),
have a particularly high risk. Without prophylaxis, approximately half of patients undergoing
elective hip or knee replacement develop VTE, although only a proportion manifests symptoms
(16). Despite newer anesthetic and surgical techniques and prophylaxis, epidemiological studies
continue to demonstrate symptomatic VTE rates persisting in the range of 1% to 3% (17, 18,
19). Overall risk of VTE in paralytic spinal cord injury is 38%, with a corresponding rate of PE
of ~5% (20).
Although the direct effect of malignancy on risk remains uncertain, the frequency of VTE
increases two- to threefold in patients undergoing surgery for malignant disease compared with
those undergoing surgery for nonmalignant conditions (21). VTE remains an important factor in
women's health. When initially introduced, oral contraceptives had an alarmingly high rate of
VTE (22). Although significantly improved, newer second- and third-generation oral
contraceptives continue to have three to four times increased risk (23). Women receiving
hormone replacement therapy also have an increased risk for VTE, with a hazard ratio of 2.1
for PE estimated by the Women's Health Initiative (24).
In addition to acquired risk factors, a variety of inherited traits contributes to the overall risk of
VTE in a patient. Although hemostatic abnormalities occur in a higher proportion of patients with
VTE in comparison to the general population (25), usually interaction with acquired risk factors
is required (26), as they remain uncommonly associated with idiopathic VTE.
CLINICAL
Clinical features vary depending on the size of the embolus and the ability of the right ventricle
to respond to increased afterload. Patients with acute massive PE may present as circulatory
collapse or even cardiac arrest. Physical findings are that of clinical shock, specifically, a cool,
clammy, and hypotensive patient with increased jugular venous pressure. The classic triad of
nonmassive PE is of sudden-onset dyspnea, chest pain, and hemoptysis, the latter two being
less commonly seen. Other clinical features include apprehension, tachycardia, cough, and leg
pain (27). However, no single clinical feature has a high predictive value (28).
Certain basic tests are important in the clinical workup for pulmonary embolus. Although chest
radiographic changes in PE are usually nonspecific, it is important in ruling out other diagnosis
including heart failure, pneumonia, and pneumothorax. Common radiographic findings of PE
include focal infiltrate, segmental collapse, and pleural effusion, although it is frequently normal
(29). Neither the oft-cited, wedge-shaped pleural opacity nor regional hypovascularity is
common. Other common basic tests with a similar lack of predictive ability include
electrocardiography and arterial blood gases (27).
A fibrin breakdown product (D-dimer assay) does have an important role in accurately excluding
PE. A raised D-dimer assay does not infer VTE as it is commonly found in hospitalized patients,
yet its sensitivity is useful as a negative
predictor (30). Newer, second-generation, rapid D-dimer tests have sensitivities ranging from
87% to 98% (31). In a metaanalysis, quantitative D-dimer enzyme-linked immunosorbent assay,
results had negative likelihood ratios <0.10, allowing for exclusion of PE in patients with a low
or moderate pretest probability (32).
TABLE 23-1 RISK FACTORS FOR VENOUS THROMBOEMBOLISM (71)
Major risk factors (relative risk, 5-20)
Surgery Major general/orthopedic surgery
Obstetrics Pregnancy
MSK Trauma
Varicose veins
Malignancy Abdominal/pelvic
Advanced metastasis
Reduced mobility Hospitalization
Institutional care
Spinal cord injury
Miscellaneous Previous venous thromboembolism
Minor risk factors (relative risk, 2-4)
Cardiovascular HTN
Congestive heart failure
Central venous catheter/pacemakers
Medications Oral contraceptives

Factor V Leiden mutation
Hereditary thrombophilia
Anti-phospholid antibody syndrome
Anti-thrombin III, protein C, protein S deficiency
Note. MSK, musculoskeletal; HTN, hypertension.
Although individual symptoms, signs, and findings on frequently performed tests do not have
sufficient accuracy, their combination, either empirically or by a scoring system, allows an
improved classification of patients suspected of having PE, into low, intermediate, and high
pretest probability (33,34).
Generally, once the pretest probability is determined a confirmatory test is performed. Until
recently, it has been a choice between a nuclear medicine ventilation perfusion (V/Q) scan and
multidetector computed tomography (CT) pulmonary angiography (CTPA). Although the V/Q
test results in less radiation and contrast, it is more ambiguous in patients, especially in patients
with underlying lung disease and the elderly (35). A normal pretest chest x-ray is required and
results are generally given as high, intermediate, and low probability. A combination of low
pretest probability and low probability V/Q test can reliably exclude PE. However, as shown in
the Prospective Investigation of Pulmonary Embolism (PIOPED) and subsequent studies, a
sufficient number of false positives exist in high-probability V/Q studies to result in a
questionable positive predictive value (36,37). An intermediate result is very common and it is
also the category with the largest amount of interobserver variability. As such, a large
percentage of patients undergoing V/Q studies require further imaging (38).
The choice for a confirmatory test remained controversial until recently, due to studies
questioning the sensitivity of first-and second-generation helical CT scanners. Studies in the late
1990s estimated the sensitivity of CT for subsegmental emboli at as low as 63% (39), although
the superiority of CT over V/Q scan was rapidly established in subsequent studies (40).
Comparison with the classic gold standard of catheter pulmonary angiography in large
published trials was rendered impractical due to the disappearance of catheter pulmonary
angiography as a reference standard. CTPA has become the de facto confirmatory test, due to
its widespread availability and ease of use (Fig. 23-1) (41).
This has led to the validity of CTPA being evaluated with a more practical methodology. A
recent meta-analysis published in JAMA evaluated 15 studies from 1994 to 2002 with a total of
3,500 patients who did not receive anticoagulation based on a negative CTPA, with a resultant
negative predictive value of a remarkable 99.4% (42). In addition, the results of a multicenter
clinical trial, the PIOPED II, await publication. Unlike PIOPED I, which used digital subtraction
angiography as a reference standard, a composite reference standard including V/Q study,
duplex ultrasound, and digital subtraction angiography is utilized in PIOPED II. In a symposium
at the annual Radiological Society of North America 90th Annual Scientific Assembly meeting in
Chicago, Illinois, preliminary results were discussed (43). Overall CTPA specificity and negative
predictive values were high (96% and 95%, respectively), with a reasonably high sensitivity and
positive predictive value (83% and 86%, respectively).
Aside from assessing the accuracy and validity of CTPA, recent research interest has shifted to
its utility in prognosis and risk stratification. Rapid hemodynamic collapse has been attributed to
a fairly poorly understood mechanism of pulmonary artery obstruction and circulating
neurohumoral substances decreasing the pulmonary vascular bed, resulting in increased right
ventricular afterload. As right ventricle and pulmonary artery pressure rises, the right ventricle
dilates, becomes hypokinetic, and ultimately fails (Fig. 23-2). In most severely affected
patients, circulatory failure develops progressively, within the first hour of an embolic event (9).
Although echocardiography is excellent at detecting right ventricle dysfunction (44), it is not a
common examination in the setting of suspected PE. However, many findings of right ventricle
dysfunction are detectable with CTPA (45). The most studied right ventricle dysfunction finding
on CTPA is the ratio of the right ventricle in comparison to the left ventricle. In a series of 431
patients, a ratio >0.9 heralded an increase in mortality by a factor of five (46). Other findings
that have been shown to have predictive power include superior vena cava and azygos vein
diameter and reflux of contrast into the inferior vena cava (IVC) (47). Right ventricle function will
only be better evaluated with the advent of ECG-gated, 64-slice, multiple-detector row CT. On
the other hand, quantification of clot burden does not appear to correlate with prognosis (48).
This is felt to be due to circulatory collapse, not only being due to high pulmonary artery
pressure but also requiring overwhelming of the ability of the right ventricle to compensate for
the high pressure.
Traditionally, patients who have not been candidates for CTPA due to either renal insufficiency
or allergies to iodinated contrast agents have been imaged with V/Q imaging. However, recent
studies have shown that gadolinium (Gd)-enhanced magnetic resonance (MR) pulmonary
angiography has been used with success, albeit with a lower sensitivity for subsegmental
embolus (Fig. 23-3) (49). A combination of MR angiography and MR ventilation and perfusion
has also been evaluated (50), but its use remains in an experimental state.
Catheter pulmonary angiography has been the traditional gold standard, although now it is
rarely performed for diagnostic purposes (51). The complication rate is low when carried out by
trained staff. Its high negative predictive value makes it a useful test in a clinical dilemma. The
presence, location, and degree of obstruction of arterial clots can be scored according to
multiple different scoring systems including the Miller clot burden score. Introduced in the
1970s, the Miller score is an angiographic severity index designed to compare the rate of
resolution of PE when heparin or fibrinolytics are used. The right
pulmonary artery has nine major segmental branches (three to the upper lobe, two to the
middle lobe, and four to the lower lobe). The left pulmonary artery has seven major branches
(two to the upper lobe, two to the lingula, and three to the lower lobe). The presence of a filling
defect or obstruction in any one of these branches scores 1 point. A filling defect proximal to
segmental branches scores a value equal to the number of segmental branches arising distally.
The maximum score is 9 for the right lung and 7 for the left lung. In addition, the score originally
evaluated the effect of embolism on PA flow, which currently cannot be assessed with CTPA.
FIGURE 23-1. Contrast-enhanced 16-slice CT examination with 0.75-mm collimation in a
48-year-old female presenting with shortness of breath demonstrates a saddle embolus
with a large clot burden: axial (A) and coronal (B) images. CT is able to identify small
subsegmental emboli confidently as in this 58-year-old female: axial (C) and oblique
coronal (D).
TREATMENT
Low Risk
Clinically PE has a wide presentation, ranging from massive PE presenting as cardiogenic
shock to incidental emboli with no adverse physiological consequences. The key to appropriate
management is risk stratification. The vast majority of patients is at low risk and has an
excellent prognosis with anticoagulation alone. Intravenous unfractionated heparin (UH) has long
been the mainstay of treatment (52). The traditional approach uses UH in an initial bolus of
5,000 to 10,000 units followed by a continuous intravenous infusion, to maintain a partial
thromboplastin time in the target range of 60 to 80 seconds. Studies have established that the
efficacy of heparin therapy depends on achieving a critical therapeutic level within the first 24
hours of treatment (53).
Low molecular weight heparin (LMWH), unmonitored and administered via a subcutaneous
route, has been available. more recently In a meta-analysis of various LMWH products versus
UFH, it was found to be at least as effective (54). Many advantages over UFH have been
touted, including its greater bioavailability; greater duration of anticoagulant effect, allowing
once- or twice-daily administration; and lower risk for induced thrombocytopenia. Although
hypothesized, no superiority of LMWH, with regard to mortality or recurrent VTE, has been
demonstrated in prospective randomized trials.
Heparin therapy is overlapped with, vitamin K antagonists such as warfarin for a minimum of 5
days and continued until the International Normalized Ratio has been within the therapeutic
range (2.0 to 3.0) for 2 consecutive days. Simultaneous initiation of heparin and warfarin
therapy is effective and allows significant shortening of hospital stays, with associated major
cost-savings (55). The obvious potential adverse event
of heparin is bleeding, with studies estimating a risk at 3 months of <3%, with a mortality rate
of <0.5% (56). Heparin-induced thrombocytopenia with thrombosis, which is more likely with
UFH than with LMWH, results in a risk for significant thrombus. If present, heparin must be
withdrawn and treatment with a direct thrombin inhibitor, such as argatroban, is necessary (57).
FIGURE 23-2. Pathophysiology cycle of major pulmonary embolism (9).
The use of thrombolytic agents has long been reserved for patients with massive PE. Meta-
analysis of previous studies, involving trials of urokinase, streptokinase, and alteplase have
demonstrated more rapid resolution of the radiographic and hemodynamic abnormalities
associated with acute PE than anticoagulant therapy alone, albeit with short-term effects (58).
However, no difference was detected in clinically relevant outcomes such as death rate or
resolution of symptoms. More recently, a subset of patients with normal hemodynamic findings
but indicators of poor outcome, such as evidence of right ventricle strain on echocardiography,
have been evaluated. Although improvements were demonstrated by a reduction of escalation
of therapy (such as mechanical ventilation) and there was evidence of a low rate of
complicating hemorrhage, no benefit in terms of mortality and morbidity was demonstrated
(59). At this time, the risk of serious bleeding with thrombolysis remains a concern, as
intracerebral hemorrhage occurs more frequently with thrombolytic agents than with heparin.
Current recommendations do not condone use of thrombolysis in hemodynamically stable
patients.
High Risk
Massive PE is life-threatening. The principal criteria to characterize acute PE as massive are
arterial hypotension and cardiogenic shock. Arterial hypotension is defined as a systolic arterial
pressure <90 mm Hg or a drop in systolic arterial pressure of 40 mm Hg for >15 minutes.
There must also be no other explanation for the hypovolemia, or presence of sepsis or a new
arrhythmia (6). Clinically shock manifests by tissue hypoperfusion and hypoxia, including an
altered level of consciousness, oliguria, and cool, clammy extremities.
It is a catastrophic event that often results in acute right ventricle failure and death, sometimes
in 1 to 2 hours (61). The pathophysiology of massive PE was briefly alluded to earlier (Fig. 23-
2). Mortality in patients is high, although it is likely underreported, as other coexistent conditions
such as congestive heart failure and coronary artery disease can obscure the
diagnosis. In an analysis of the ICOPER trial data by Kucher et al. (62), among 2,392 patients,
108 (4.5%) met the above-mentioned criteria for massive PE. The 90-day mortality rate was
52.4%. Other studies have reported a mortality rate increasing with degree of hemodynamic
compromise (Table 23-2). This PE Registry included 1,001 patients from 204 German centers
and reported an overall mortality of 15% (63). In the face of such high mortality and the
potential for rapid decompensation, more aggressive treatment than standard pharmacologic
therapy may be justified. As such, rapid recognization of a patient with massive PE is
imperative.
FIGURE 23-3. Coronal three-dimensional, T1-weighted with fat saturation image obtained
after administration of 40 mL of gadolinium. Forty-one-year-old male, status post renal
transplant, with acute onset of shortness of breath. The hypodense tubular structure at the
bifurcation of the right main pulmonary artery is consistent with pulmonary embolism.
Presenting symptoms of massive PE include severe dyspnea with anxiety and syncope.
Physical examination may be nonspecific and reveal no more than tachypnea and tachycardia.
However, evidence of right ventricle failure such as distended neck veins, parasternal heave,
and right ventricular gallop should be looked for. Other laboratory examinations in the standard
PE workup are not proven to be helpful in risk stratification and, more importantly, waste
valuable time. Yet other serum markers can be elevated in the setting of massive PE. Troponin
is elevated in 30% to 40% of patients with moderate to large PE (64). Another serum marker
under investigation is brain natriuretic peptide. The mechanism is thought to be release of
ANP/brain natriuretic peptide by stressed ventricular cells in response to increased filling
pressures (65). Echocardiogram may reveal findings suggestive of hemodynamically significant
PE. In a study of 317 patients with clinically suspected PE, the 1-year mortality was 13% in
those with evidence of RV dysfunction, versus 1.3% in those without (66).
TABLE 23-2 IN-HOSPITAL MORTALITY ACCORDING TO THE DEGREE OF

HEMODYNAMIC COMPROMISE IN 1,001 PATIENTS WITH ACUTE
PULMONARY EMBOLISM (62)
Category N Mortality (%)
Right ventricular overload 407 8.1
Pulmonary hypertension
Arterial hypotension 316 15.2
Cardiogenic shocka 102 24.5
Cardiopulmonary resuscitation 176 64.8
a Patients with arterial hypotension accompanied by cardiogenic shock or judgeed by
the attending physicians to require the administration of catecholamines

Supportive
Due to the high mortality rate of PE, high-dose UH should be administered to achieve rapid
therapeutic levels. A bolus of 500 to 1,000 mL isotonic saline may be initially administered. This
may be useful in patients with low end-diastolic right ventricle volume. However, caution must
be used in patients with compromised right ventricle function, as increased wall stress may
critically intensify right ventricle ischemia (67). Inotropic agents are the first-line treatment for
PE-related shock. No one agent has been found to be more advantageous, and treatment
protocols vary from center to center.
Thrombolysis
As noted earlier, thrombolysis is not recommended for all patients presenting with PE. It is
recommended as first-line treatment for patients with massive PE (55). Only one randomized
trial has been performed for patients with massive PE. In this small trial, involving eight patients,
all four patients given thrombolysis (streptokinase) survived, while all four given heparin died
(68).
TABLE 23-3 SUBGROUP ANALYSIS OF TRIALS THAT INCLUDED

HEMODYNAMICALLY UNSTABLE PULMONARY EMBOLISM (PE) (61)
Outcome Thrombolysis (n = 128) Heparin (n = 126) OR (95% CI)
Recurrent PE or death 12 (9.4%) 24 (19.0%) 0.45 (0.22-0.92)
Recurrent PE 5 (3.9%) 9 (7.1%) 0.61 (0.23-1.62)
Death 8 (6.2%) 16 (12.7%) 0.47 (0.20-1.10)
Major bleeding 28 (21.9%) 15 (11.9%) 1.98 (1.00-3.92)
Note. OR, odds ratio; CI, confidence interval.
A recent meta-analysis, published by Wan et al. in 2004 (69), reported on 11 randomized trials
including 748 patients with PE. Analysis of all 11 trials confirmed previous meta-analysis results,
in that thrombolytic therapy in comparison with heparin alone resulted in a nonsignificant
reduction in recurrent PE or death. However, in a subgroup analysis of the five trials that
included patients with massive PE (Table 23-3), thrombolytic therapy was associated with a
55% reduction in risk of death. These results are in keeping with previous meta-analyses and
guidelines, but a large randomized controlled trial remains necessary, to identify the subgroup
of patients with PE for whom the benefits of thrombolytic therapy outweigh the risks.
The most common thrombolytic drugs are urokinase, streptokinase, and alteplase. Alteplase is
currently the recommended drug, due to its wide availability and the possibility of exacerbation
of hypotension with streptokinase. Reteplase, a newer agent, appears promising. It is
administered as two separate doses of 10 units, one at baseline and another at 30 minutes. In
comparative studies with alteplase no difference has been found in any measured pulmonary
hemodynamics (70). Reteplase is not currently approved for use for PE in the United States,
although it is available for myocardial ischemia.
Recent guidelines recommend bolus-dose alteplase for treating massive PE (55,71). However,
the safest and most effective treatment regime remains unknown. A recent meta-analysis of 26
trials, including 1,025 patients (72), comparing efficacy of infusion alteplase, bolus-dose
alteplase, and streptokinase demonstrated no significant differences, although crude analysis
raised possible mortality benefit with alteplase. Current standard protocols are reported in
Table 23-4. All agents are administered through a peripheral IV. During treatment no heparin is
given for streptokinase, although it is optional for alteplase/reteplase. Since all protocols are
short, testing for fibrinogen, fibrin split products, and thrombin time is not mandatory.
TABLE 23-4 SYSTEMIC THROMBOLYSIS: PROTOCOLS
250,000 U over 30 minutes followed by 100,000

Streptokinase 1977
U/hour for 24 hours
Urokinase (currently 4,400 U/kg over 10 minutes followed by 4,400

1978
unavailable) U/kg/hr for 12-24 hours
Reteplase 100 mg over 2 hours 1990
Note. All agents administered via peripheral IV.
The major complication of thrombolysis is hemorrhage, although allergic reactions, fever, and
nausea and vomiting may occur (73). Overall risk of major hemorrhage in all patients treated
with thrombolytic therapy in the meta-analysis by Wan et al. was 9.1%, versus 6.1% for
patients treated with heparin. Within the subgroup analysis of patients with massive PE, the
incidence of major bleeding more than doubled, to 21.9%, versus 11.9% for heparin. The most
feared bleeding complication is intracerebral hemorrhage, with a reported incidence ranging
from 0.6% to 3% (74). The risk factors associated with intracranial bleeding are increasing age
(0.4% at <65 years and 2.1% at >75 years), increasing dose of thrombolytic, chronic
hypertension, and low body mass (75). Understandably, the risk of bleeding largely defines the
contraindications of thrombolysis; these include active internal bleeding, history of
cerebrovascular accident, recent intracranial or intraspinal surgery or trauma (90 days), known
bleeding diathesis, and severe uncontrolled hypertension. Hepatic or renal failure, pregnancy,
puncture of a noncompressible vessel, and pericarditis are additional relative contraindications
(76).
Catheter-Directed Thrombolysis
Several investigators have treated pulmonary PE with intrathrombus delivery of thrombolytic
drugs in an attempt to maximize the thrombolytic effects and minimize the required dose of the
drug and complications. This assumption is based on the experience with catheter-directed
thrombolysis of peripheral arterial bypass grafts and dialysis fistulas supported by results from
certain animal models of PE showing superiority of direct intrathromubus delivery (77).
However, this assumption has been contradicted by other studies, also in animal models, which
have shown that thrombolysis has equal effects when given peripherally or when administered
through a catheter positioned within the thrombus (78).
Four small studies have been published to date, three using urokinase and one alteplase (79,
80, 81, 82). All of these studies showed significant improvement, with the largest reporting safe
use of this technique in 13 postoperative patients using urokinase and heparin, resulting in 98%
clot lysis with no deaths or bleeding complications (78). These authors used a loading dose of
2,200 IU urokinase/kg followed by a continuous infusion of 2,200 IU/kg/hour for up to 24 hours,
with concomitant use of heparin at a rate of 500 U/hour. The other three studies showed similar
results with regard to clot lysis and clinical improvements. However, all eight patients treated
with alteplase had a higher incidence of bleeding, with three requiring transfusions. Those
authors gave a bolus of 10 mg followed by continuous infusion at 10 mg/hour for 4 to 9 hours
up to a maximum dose of 100 mg. Nevertheless, no recent large studies have been performed
and recent guidelines do not recommend the use of catheter-directed thrombolysis (55).
Surgical Embolectomy
Open embolectomy continues to be performed in emergency situations when more conservative
measures have failed. Operative mortality in the era of immediately available cardiopulmonary
bypass has ranged from 16% to 50%, with a recent review of 14 studies with 756 patients
identifying a mortality rate of 32% (83). In patients who have had cardiopulmonary arrest,
mortality has been reported as between 50% and 94%. These numbers are lower at dedicated
centers; a recent retrospective review of 47 cases resulted in an in-hospital mortality rate of
6% at 30 days (84). However, inclusion criteria for surgery were more liberal, with 15 (32%)
treated for right ventricular dysfunction as opposed to the traditional contraindication to
thrombolysis. However, surgical embolectomy is not ubiquitously available and only a few
centers have extensive experience with this procedure. This was one of the major impetuses for
the development of percutaneous devices for the treatment of massive PE.
Percutaneous Thrombectomy
The only alternative to thrombolysis or surgical embolectomy for massive PE is percutaneous
catheter thrombectomy (85). This procedure can be performed with a heterogeneous group of
devices and techniques designed to clear intravascular thrombus by use of a combination of
mechanical dissolution, fragmentation, and aspiration. The features and benefits of multiple
devices have been enumerated in a number of publications (86,87). An ideal percutaneous
device has to have multiple features to be effective. These include high maneuverability,
allowing rapid access of the pulmonary artery. It must be easily steerable and have a low
profile in order to access multiple segmental arteries if necessary. Rapid, effective, and
nontraumatic clot removal is a must. Minimal blood loss and hemolysis are important issues, as
many of these patients are ill with possible renal insufficiency.
Most of the devices do not completely eliminate the thrombi but, rather, break them into smaller
fragments, which migrate distally, allowing improvement in pulmonary perfusion. The rationale
of this technique is that the peripheral vascular system has a much larger cross-sectional area,
leading to less obstruction and pulmonary vascular resistance (88). Frequently, mechanical clot
fragmentation is followed by catheter-directed thrombolysis, which appears to be more
efficacious due to the increased surface area of the thrombus exposed to the thrombolytic drug
(89,90).
Many devices have been developed for the peripheral arterial system and adapted for use in
the pulmonary arteries. Many have not garnered widespread use and no one device or method
is accepted among the interventional community.
Multiple methods of categorization have been used. The main classification has been into the
following categories.
1. Percutaneous aspiration thrombectomy/pull-back thrombectomy
2. Recirculation devices
a. Mechanical recirculation
b. Venturi/hydraulic recirculation
3. Mechanical fragmentation
Percutaneous aspiration thrombectomy and other aspiration and pull-back thrombectomy
techniques/devices have been used for a relatively long time. However, they are not currently in
widespread use as stand-alone techniques. For the most part, they are most often used in
conjunction with other techniques or more modern devices.
Percutaneous aspiration thrombectomy was introduced over 20 years ago (91). It can be
performed using a variety of generic wide-lumen catheters. Ideally a vascular sheath with a
removable hemostatic valve is used to prevent retention of aspirated thrombus inside the
sheath while retracting the catheter from the artery. To achieve powerful suction, a 50-mL
syringe with a Luer lock connector is needed. The procedure can be repeated several times to
remove the entire thromboembolic material (Fig. 23-4). Problems with blood loss can occur. In
addition, the risk of antegrade dissection increases significantly with repeated catheter
advancement, in the peripheral arterial literature (92). Percutaneous aspiration thrombectomy
has been primarily used as an adjunctive technique in the setting of PE.
Lang et al. (5) described a variation of this technique in 1997. Following mechanical clot
maceration with a moving 7-Fr curved pigtail catheter, a 14-Fr nontapered catheter was used
as a suction catheter. It was mounted coaxially over a 6-Fr guiding catheter, which was used to
provide stiffness and stepwise taper necessary for advancement past the pulmonary valve. The
suction catheter was advanced into the clot and a 30- and a 50-mL syringe was applied to
remove the clots. Each procedure was repeated one to three times per side. The procedure
was attempted with success in three patients. However, no further reports of this method have
been identified in the literature.
The Greenfield transvenous pulmonary embolectomy catheter was the first device designed for
the treatment of PE, in 1969. The postmodification device is a 12-Fr, braided, double-lumen,
steerable catheter with a large control handle. It is designed to be used through a 16-Fr sheath
or a venotomy. Five-millimeter or 7-mm radiopaque suction cups are used to manually suction
out the clot. The device must be removed as a whole each time.
The device was used by the inventor on 46 patients over a period of 22 years. Emboli were
extracted in 76% of the patients, with a 30-day survival rate of 70% (94). Other investigators,
reporting on their experience with the device over a period of 7 years in 18 patients, reported
clinically perceptible success in 11 patients (95). Drawbacks of this device include bulkiness,
difficult steerability into lobar branches, and risk of thrombus dislodgment and cardiac chamber
perforation.
Recirculation Devices
These devices mechanically fragment the thrombus locally within the artery into pieces that are
small enough to pass the capillary bed or use additional features to remove the pieces from the
body. Embolization of large pieces may occur.
The Clot Buster Amplatz thrombectomy device (Microvena Corp., White Bear Lake, MN)
consists of an 8-Fr catheter with a 1-cm-long metallic capsule mounted on its distal end. The
capsule houses a coaxial impeller that is rotated at 150,000 rpm by a compact air turbine.
Adjacent thrombus becomes entrapped by the vortex into the end hole of the capsule, where it
becomes fragmented by the rotating impeller blades before recirculating out from the capsule's
three side holes.
In vitro studies showed that the Amplatz thrombectomy device could liquefy 99.2% of 4-day-old
thrombus and 98.8% of 10-day-old thrombus, into particles smaller than 1,000 m, the vast
majority smaller than 400 m (96). Its use has been reported in five patients (one with marked
and three with moderate improvement in pulmonary perfusion, one without change; this patient
later died). The use of the device resulted in hemolysis in all five patients, but without
development of renal failure. In patients with renal impairment, the authors recommend
restriction of the device activation time to 5 minutes (97). The authors also recommended
modifications of this device to make it more effective and safer in the pulmonary circulation.
These
included over-the-wire capability to improve maneuverability and more power to increase clot
maceration.
FIGURE 23-4. A 48-year-old male with acute pulmonary embolism and right ventricle
strain. Digital subtraction (A) and nonsubtraction (B) right pulmonary artery angiograms
were performed, demonstrating a significant embolus in all segmental arteries. Following
suction thrombectomy, there was significant improvement in the lower lobar artery.
Recently, an experimental study published by Kucher et al. (6) described in vitro and canine in
vivo experience with a new device specifically designed for the treatment of massive PE. The
Aspirex device (Straub Medical, Wangs, Switzerland) consists of a central high-speed rotational
coil within the catheter tip, creating negative pressures, with the intent of aspiration of thrombus
and maceration. The catheter has a hollow lumen designed to remove the macerated thrombus.
It is an over-the-wire catheter designed with a flexible tip for possible selective advancement
into proximal pulmonary arteries. It can be considered a progeny of the Amplatz thrombectomy
device.
FIGURE 23-5. A: Large embolus in right upper lobar artery and lower basilar segmental
arteries. B: Following AngioJet thrombectomy there was significant improvement in the
upper lobar artery and in a lateral basilar segmental artery.
During in vitro testing involving porcine thrombus in 14-mm test tubes within a previously
described PE test system (99), a mean aspiration time of 69 seconds was required for
complete aspiration. No macroembolization was identified, although microembolization was
quantified at 1.9 g. In vivo testing involved 10 pigs. Catheter thrombectomy was performed
immediately following thrombus injection and hemodynamic evidence of embolism. The end
point of thrombectomy was either a mean aortic pressure returning to >70 mm Hg or a mean
pulmonary arterial pressure decreasing to <25 mm Hg. Angiographic results were not utilized
as an end point. The average amount of aspirated fluid was 137 46 mL. The mean procedure
time was 32 minutes, with a range of 20 to 55 minutes. There was angiographic improvement in
all vessels. On average mean pulmonary arterial pressure decreased from 33 to 22 mm Hg.
The device suffers from similar limitations as do all recirculation devices, in that there is blood
loss and possibility of hemolysis. It remains to be seen if this device will see widespread use.
In recent years Hydraulic/Venturi recirculation -type devices have enjoyed increased popularity.
The AngioJet (Possis, Minneapolis, MN) is the prototypical recirculation device, which relies on
the Venturi principle. The device is based on industrial technology using high-pressure jets to cut
concrete. Since its introduction in 1992 it has undergone multiple refinements (100).
The device consists of three components: a permanent drive unit, a one-use-only pump set, and
the catheter itself. Multiple versions are offered, in different lengths and diameters. The device
is suitable to treat vessels from 2 to 12 mm in diameter. It consists of a catheter with a large
primary lumen (for debris evacuation and guide-wire passage), and a small profiled stainless-
steel tube supplying a pulsatile pressurized solution (40 to 60 mL/minute, depending on the
catheter) from a reusable pump drive system. The stainless-steel tube projects beyond the
catheter tip in the form of a transverse loop with three fine orifices (~50 m) that direct three
high-speed retrograde fluid jets toward the end hole of the evacuation lumen. In the gap zone
(the space between the distal loop and the end hole of the aspiration lumen), the high-speed
retrograde fluid jets (350-450 km/hour) create an area of low pressure (Venturi effect),
resulting in a zone of hydrodynamic recirculation that pulls and fragments adjacent thrombus by
the resulting high shear forces (Fig. 23-5).
In an in vitro flow setup, an early model (AngioJet F105) cleared and/or dissolved the bulk of
treated thrombus, with 12% of the initial thrombus volume released distally in the form of
particles (99.8% smaller than 10 m) (101). This study also evaluated the extent of endothelial
damage resulting from AngioJet thrombectomy in 15 canine vascular segments and compared it
to damage in 4 vascular segments subjected to Fogarty balloon pull-back thrombectomy and 10
untreated vessels. Comparing endothelial denudation under the scanning electron microscope,
AngioJet-treated vessels had greater mean residual endothelial coverage (88% 7.9%) than
Fogarty balloon thrombectomy (58% 8.0%; p < 0.0002). The authors concluded that AngioJet
resulted in less endothelial damage.
This device has become the device of choice for many interventional practitioners. Aside from
multiple clinical reports in the literature (101, 102, 103, 104), two larger reviews recently
published explored the utility of this device in treating massive PE. In a retrospective case
report involving 17 patients, by Zeni et al. (7), all patients had hypotension with the diagnosis of
PE. Six of the patients had contraindication to thrombolysis. The patients were treated with a 6-
Fr Xpeedior RTF device through an 8-Fr sheath. Sixteen of 17 had immediate clinical
improvement. One patient died during the procedure due to hemoptysis and another died within
the first 24 hours, due to recurrent PE. In long-term follow-up 2 patients were lost to follow-up;
8 of
13 were asymptomatic, 4 had dyspnea on exertion, and 1 was on home oxygen.
Interestingly, during the procedure one patient suffered third-degree heart block necessitating
termination of the procedure and one patient had bradycardia requiring Lidocaine. This is a
phenomenon that has been identified with the use of the AngioJet in other vascular beds,
although it has been conjectured to be due to hemolysis and the release of adenosine, which
remains controversial (103). Slightly clouding the results is the fact that after the procedure the
10 patients with no contraindications to thrombolysis were left with catheter-directed
thrombolysis for a period of time.
A similar retrospective review compared eight patients treated with catheter-directed
thrombolysis alone and six subsequent patients treated with AngioJet and catheter-directed
thrombolysis (104). Both arms were successful in reducing the Miller clot burden score,
however, the AngioJet arm utilized less thrombolysis and was much quicker. However, one
patient did die during the AngioJet procedure due to recurrent PE. Aside from the reports of
bradyarrhythmias, a concern with AngioJet, shared with other mechanical recirculation devices,
is the possibility of blood loss with hemolysis, causing an increased burden on renal function in
severely ill patients. At a minimum, the concern for hemolysis results in limitation of use. Cost is
an issue as well, as the AngioJet, unlike other recirculation devices working on the Venturi
principle, requires purchase of a separate expensive pump unit.
The Hydrolyser system (Cordis, Johnson and Johnson) has been in clinical use since 1993. The
device has either a 6- or a 7-Fr double-lumen, 65-cm-long catheter with a 6-mm oval side hole
4 mm from the distal tip. The smaller injection lumen ends in a hairpin loop at the device tip.
Heparinized saline is injected through the injection lumen by an angiographic pump at a rate of 3
mL/second at 750 psi and is directed by the hairpin loop in a retrograde direction into the
exhaust lumen. At the site of the oval side window this saline jet creates the Venturi effect,
which sucks adjacent thrombus into the hole and disrupts it. The over-the-wire device has
better steerability, but there is also a slight reduction in size of the exhaust lumen. The Oasis
thrombectomy system (Boston Scientific) is similar to the Hydrolyser catheter, is available in 6-,
8-, and 10-Fr sizes and in multiple lengths, and accepts an 0.018-in. guide wire. The few case
reports published have shown encouraging results (105,106). The most recent study, of seven
patients treated during cardiopulmonary resuscitation, showed the remarkable success rate of
85.7%, with only one patient dying during the procedure. These results remain to be duplicated
from other centers. Disadvantages include possible fluid overload and hemolysis, similarly to
the other rheolytic thrombectomy catheters. Another disadvantage is the eccentric location of
the opening at the catheter tip, resulting in a suction vortex of <360 degrees. In vitro studies to
visualize flow patterns have demonstrated a clearly visible vortex formed in a localized area
around the side hole of the catheter tip, which may result in a tenting effect (107). Also, a
standard pressure pump is utilized, meaning that there is a limit to the amount of fluid that can
be pumped. The efficacy of these two devices was also questioned in a study involving porcine
models in 2001 (108). In seven pig models with central emboli, minimal angiographic
improvement was seen, with no significant hemodynamic improvement. In addition, the
procedure resulted in an increase in free hemoglobin levels.
Mechanical Fragmentation
The Arrow-Trerotola (Arrow International, Reading, PA) is a low-speed fragmentation, non
recirculation thrombectomy device. It is available as a 7-Fr, over-the-wire, 120-cm device or a
5-Fr, 65-cm device. Both have fragmentation baskets 9 mm in diameter. Much research has
been performed regarding the effectiveness of the device in fistula declotting (109, 110, 111).
However, there is scant literature on its use for massive PE.
A study evaluating a slightly modified Arrow-Trerotola device for treatment of acute PE in a
canine model was published by Brown et al. (112). Iatrogenic unilateral massive pulmonary
emboli were created in nine canines. These pulmonary emboli were treated with an over-the-
wire device in an 8-Fr constraining catheter. Immediately following creation of the thrombus the
device was utilized, requiring one to five passes, with activation times ranging from 18 to 61
seconds. One major adverse reaction occurred, involving entanglement of the device with a
pulmonary artery, with subsequent inability to remove the device. Although no gross
extravasation occurred, subsequent histological assessment identified intimal injury ranging from
75% to 90% full thickness.
In the only human case report published to date a large, left, 75% occlusive PE was treated
with the Arrow-Trerotola device (113). The device was able to improve flow in an upper lobe
branch, although a large amount of occlusive thrombus remained. Although the pulmonary
pressure remained unchanged, there was clinical improvement. Due to the nonrecirculation
nature of the device, no thrombus fragments are removed. However, in vitro studies have
shown that 95% of the fragments produced by the Arrow-Trerotola device are <2 mm (114). In
addition, multiple studies continue to enumerate the endothelial damage caused by the Arrow-
Trerotola device due to its mechanism of action (115).
Another version of a mechanical thrombectomy device that works by fragmentation is the
rotatable pigtail catheter. No mass-market device is available. Instead, the reported devices
have usually been modified high-torque 5-Fr pigtail catheters. An oval side hole, in the outer
aspect of the pigtail loop, allows for direct passage of a guide wire to act as a central axis
around which the catheter rotates. The rationale has been the ease of handling of the device
and it is felt to be the safest configuration for probing the pulmonary arteries.
The catheter is generally used manually. Experimental work with animal models was performed
in the late 1990s (116). Schmitz-Rode et al. first reported their clinical experience (8) through a
prospective five-center study that involved 20 patients with severe hemodynamic impairment
and massive pulmonary emboli. Total fragmentation time was relatively minimal, at 17 8
minutes. In patients who did not receive thrombolysis until after intervention (15 patients), the
shock index and pulmonary arterial pressure both decreased significantly. However, overall
mortality was 20%, as three patients died due to right ventricular failure despite successful
angiography results. The remaining patients had no adverse clinical outcomes. As the learning
curve increased in this study two separate catheters were utilized, a 12-mm pigtail catheter for
the main pulmonary artery and then an 8-mm-diameter catheter for the lobar arteries.
Further clinical reviews continue to be published, although neither significant technological
advancements nor commercial versions have been produced (118,119). De Gregoria et al.
presented a retrospective review of 59 patients treated for massive PE. Of this population, 23
were in shock, whereas the rest had a primary presentation of syncope or dyspnea. Mean
pulmonary pressure prior to treatment was 42 mm Hg. All patients underwent fragmentation
with a curved pigtail catheter. An angioplasty balloon was utilized in four patients and two
patients were treated with a basket system. Urokinase was administered for 24 hours in 57
patients. Patients were evaluated with repeat angiography 12 to 24 hours following the initial
procedure. Clinical improvement was seen in 56 patients (94.9%). Two patients died during the
procedure and another died in the Intensive Care Unit within 24 hours. The overall
mean posttreatment arterial pressure was 28.1 mm Hg, a significant decrease of 48%. No
major complications were reported, aside from minor hematomas at the puncture site in eight
patients.
This hybrid method of aggressive fragmentation and catheter thrombolysis has been reported in
a recent Japanese study. They treated 25 patients in a similar manner, with improvements in
the Miller score and mean pulmonary arterial pressure, from 32.6 to 23.4 mm Hg. They
identified no treatment-related deaths. One major complication was cardiac arrest during
treatment, with subsequent recovery. Other complications have been reported in the literature
including dislocation of clot resulting in worsening of hemodynamic parameters (120).
CONCLUSION
PE is very common. For the majority of patients, anticoagulation is sufficient for treatment.
However, a significant subset of patients deemed to have massive PE has a much higher rate
of mortality. CTPA is rapidly emerging not only as a reliable diagnostic test, but also as an
important prognostic test. With more rapid and reliable risk stratification, thrombolysis is
becoming an accepted treatment for those in the highest risk category. Unfortunately, due to
the nature of risk factors, many patients have contraindications to thrombolysis. It is in this
subset of the population that alternatives such as surgical embolectomy and percutaneous
thrombectomy are required. Although in recent studies surgical intervention has been shown to
be safer than previously thought, with a decreased rate of mortality at dedicated centers, it is
not a widely available option.
Percutaneous devices continue to develop rapidly, with widespread use in other vascular
applications such as peripheral arterial disease and fistula maintenance. Their use in the
pulmonary vascular system has perhaps lagged, due to the unique characteristics and
challenges of this vascular bed. Yet over the past 15 years numerous small studies have shown
benefit, and now, with maturation of the industry, dedicated devices are emerging. However,
the literature remains scant and large series of patients are required to validate the use of
these devices.
Based on the current knowledge, the use of endovascular techniques should be restricted to
patients with severe hemodynamic compromise who are not candidates for systemic
thrombolysis or surgical embolectomy. The decision to treat should ideally be made by a
multidisciplinary team of pulmonologists, cardiologists, cardiac surgeons, and interventional
radiologists. Due to the complexity of the procedure, intervention should only be performed by
physicians with extensive experience in endovascular pulmonary angiography and intervention.
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> Table of Contents > Section III - Vascular Interventions > Part B: - Systemic Venous Interventions > Chapter 24 - Inferior Vena
Cava Filters
Chapter 24
Inferior Vena Cava Filters
Hanno Hoppe
John A. Kaufman
Each year there are an estimated 1,359,000 new cases of venous thromboembolism (VTE) in
the United States (1). Systemic anticoagulation with oral, parenteral, or subcutaneously injected
pharmacologic agents is the conventional treatment of VTE. The objectives of anticoagulation
are prevention of thrombus propagation, prevention of pulmonary embolism, and restoration of
patency of the thrombosed veins. In patients with VTE and contraindications to anticoagulation,
interruption of the inferior vena cava (IVC) to prevent pulmonary embolism (PE) has been
practiced for over 100 years (2).
A major open surgical procedure was required with the initial caval interruption techniques for
ligation or plication of the infrarenal IVC. In the 1950s a simpler approach was introduced,
which was constriction of the IVC lumen by surgical placement of an external clip (2). The high
morbidity and mortality of surgical interruption of the IVC (4%-18%) limited utilization and
subsequently stimulated development of less invasive endoluminal techniques. A large occlusion
balloon was an early device used for this purpose (3). The balloon was introduced through
surgical venotomy and created complete IVC obstruction. In 25% of patients, symptomatic
lower extremity edema occurred. The Mobin-Uddin umbrella filter (Edwards Life Sciences) was
introduced in 1967 and became the first clinically and commercially successful intraluminal
device for partial IVC interruption (4). This device consisted of perforated silastic webbing with
radially arranged stainless-steel arms to create a cone-shaped filtration device. This filter was
placed in the IVC with the apex of the cone pointing toward the patient's feet and had an
unacceptably high rate of symptomatic IVC thrombosis. Consequently, the Mobin-Uddin filter
was withdrawn from the market in the 1980s. In 1973, the introduction of the Kimray-Greenfield
vena cava filter (latter known simply as the Greenfield Filter [GF]; Boston Scientific, Natick,
MA) marked the beginning of widespread clinical adoption of partial caval interruption.
The GF consists of six stainless-steel arms arranged to form a cone (Fig. 24-1). The filter was
placed through a surgical cutdown on the jugular or femoral vein using a 29-Fr-outer diameter
(OD) delivery system with the apex of the cone oriented toward the patient's heart. Insertion of
the device through a venotomy resulted in a lower morbidity than plication of IVC or clip
placement, and clinical results were excellent. Percutaneous placement using large dilators or
angioplasty of the venous puncture site proved even safer, resulting in rapid adoption by both
interventional radiologists and surgeons (5,6). The clinical performance of this device has
become the benchmark for subsequent vena cava filters based on extensive experience with
the GF (7, 8, 9).
With approximately 100,000 placements in 2003, filter utilization in the United States has grown
steadily over the last 20 years (10). In most hospitals, percutaneous vena cava filter insertion is
a routine procedure. Of interest, utilization outside of the United States remains relatively low.
There are currently 11 different filters available in the United States. All of these devices are
constructed for permanent use in the IVC, but some have been designed with the capability to
be safely retrieved within a predetermined time frame (so-called optional filters).
THE ROLE OF INFERIOR VENA CAVA FILTERS IN TREATMENT

OF VENOUS THROMBOEMBOLIC DISEASE
The primary intention of vena cava filters is to trap and retain large fragments of venous
thrombus to protect the pulmonary arterial circulation. Filters neither prevent deep venous
thrombosis nor enhance the pharmacologic treatment of VTE. Secondary and adverse filter
outcomes include filter occlusion, migration, fracture, penetration, and infection. Besides
technical problems or errors during filter placement can contribute to adverse outcomes.
Measurements of filter performance should be concentrated on prevention of pulmonary emboli
but also include all customary parameters used to follow implantable medical devices.
CHALLENGES IN THE EVALUATION OF DIFFERENT DEVICES

Design and composition of the ideal filter has been the subject of much opinion but relatively
little scientific investigation (11). One of the primary explanations for this is the lack of objective
clinical data on vena cava filters. To date there has been one prospective randomized clinical
study of filters (12,13). Other published reports are either descriptions of series, historically
controlled, or anecdotal reports. An additional major drawback is the lack of a uniformly
accepted model for in vitro or vivo testing (14, 15, 16, 17, 18, 19, 20). When designing a
model, the range of hemodynamic variations, characteristics of emboli and embolic events,
perifilter fluid dynamics, and hematologic responses present major challenges. The most
appealing in vitro models at a hypothetical level are those including a distensible IVC, pulsatile
flow, inflow from branch veins, and ability to test in both supine and upright positions.
FIGURE 24-1. Stainless-steel Greenfield filter (Boston Scientific Inc).
PERMANENT VENA CAVA FILTERS
Greenfield (Boston Scientific, Natick, MA)
The original 29-Fr stainless-steel GF is no longer produced. A low-profile titanium version of the
Greenfield filter (TGF) retaining the six-leg cone shape was introduced in 1989 (Table 24-1).
This device was designed for percutaneous delivery through a 14-Fr-OD sheath. As for the GF,
the maximal caval diameter appropriate for the device is 28 mm. An early problem with IVC
penetration by the legs and splaying of the filter resulted in a modification of the hooks to the
current design (Fig. 24-2). Although there is a tendency for asymmetric leg distribution, this has
not been shown to be clinically important (21). A stainless-steel over-the-wire version of the
lower profile Greenfield filter (SSGF) was released in 1995, and leg clustering has been less of
an issue with this device (Fig. 24-3). Both filters are supplied preloaded in access-specific
(femoral or jugular) kits with deployment handles that are simple to use.
Bird's Nest Filter (Cook Inc., Bloomington, IN)

The Bird's Nest device was the first filter designed specifically for percutaneous placement (Fig.
24-4). When first introduced in 1982, the delivery system was much smaller than the available
original GF (14 versus 29 Fr). One remarkable benefit of the smaller delivery system was less
local trauma to the femoral or jugular vein (22). Subsequently all new IVC filters have been
designed for percutaneous introduction. Besides a low-profile delivery system, the filter has
several unique aspects (23). To date the Bird's Nest filter is the only filter approved for
placement in a vena cava with a diameter up to 40 mm. The mechanism of filtration is based on
a wire mesh that is formed in a random pattern between a pair of leading and trailing anchoring
struts. Once the leading anchors are set the delivery system is withdrawn slightly and the wire
is extruded from the delivery sheath until the trailing struts approach the end of the sheath. At
this point the filter can be completely withdrawn into the sheath by pulling back in the pusher
wire (24). The delivery system is then advanced as a unit to overlap the struts 20% to 30%, to
compact the wire mesh. Once the trailing struts are released the pusher wire is unlocked from
the filter. Since there is no uniformity of mesh formation, prolapse of some strands central to
the anchoring struts is common but of no known clinical significance subject to the condition that
they remain outside of the heart (25). In magnetic resonance imaging (MRI) examinations, the
concentrated stainless-steel wire results in a large area of signal loss. The only substantial
difference between the femoral and the jugular kits is the length of the preloaded delivery
catheter.
LGM Vena Tech Filter (B. Braun Medical, Bethelehm, PA)

Approved for use in the United States in 1989, this filter had previously been available in Europe
(Fig. 24-5). The device is constructed from Phynox sheet metal, with a six-strut central cone
anchored and centered with ski-like extensions from each filter leg. The filter is loaded into the
delivery sheath from a capsule and is then advanced into position using a pusher catheter. The
final deployment is accomplished by stabilizing the pusher catheter and withdrawing the sheath.
There is no shortening with deployment. The filter is approved for a maximum IVC diameter of
28 mm.
Vena Tech LP (B. Braun Medical)

This second-generation Vena Tech filter was approved for use in the United States in 2001 (Fig
24-6). The Vena Tech LP shares its basic design with the first-generation device but is
constructed from Phynox wire rather than sheet metal. In addition, the new filter has eight
rather than six legs and the stabilizing extensions are joined at the apex. The filter is delivered in
a manner identical to the original device, using the same diameter system. Although the filter is
approved for use in IVCs up to 28 mm in diameter, it is identical to the device used in Europe,
which is approved for a maximal caval diameter of 35 mm.
Simon Nitinol Filter (CR Bard, Tempe AZ)

The Simon Nitinol Filter, which was approved in 1990, was the first medical device to take
advantage of the thermal memory properties of Nitinol (Fig. 24-7). The filter is constructed from
Nitinol wire that forms a bilevel filtration device when placed in the body and can be elongated
at room temperature and delivered through a 9-Fr outer diameter sheath. After the filter is
advanced to the end of the sheath with a pusher wire, it can be deployed by stabilizing the wire
and withdrawing the sheath. When placed using a femoral approach, the seven petals form
first, with a large amount of shortening as the elongated wires collapse into the looped petal
configuration. Some operators first reform the petals below the intended final deployment level
and then advance the partially deployed device into position while the feet are still in the
catheter, which is called two-step delivery. The six anchoring legs do not shorten with delivery.
Jugular or brachial delivery reduces the impact of shortening of the petals as the anchoring legs
are deployed first.
TABLE 24-1 TECHNICALINFORMATION ON COMMERCIALLY AVAILABLE

CAVAL FILTERS
Sheath Maximum
Filter Manufacturer outer Retrievable Access caval Metal
diameter diameter
24-Fr Boston RFV, 28 Stainless-

28 Fr No
Greenfield Scientific RIJ mm steel wire
Titanium Boston RFV, 28 Titanium

14.3 Fr No
Greenfield Scientific RIJ mm wire
12-Fr RFV,
stainless- Boston LFV, 28 Stainless-
steel 15 Fr No RIJ,
Scientific mm steel wire
Greenfield LIJ
RFV,
Bird's LFV, 40 Stainless-
Cook 13.8 Fr No
Nest RIJ, mm steel wire
LIJ
RFV,
Yes
Gnther LFV, 30
Cook 10 Fr (jugular Elgiloy wire
Tulip RIJ, mm
access)
LIJ
7-Fr RFV,
Yes
jugular, LFV, 30
Celect Cook (jugular Conichrome
8.5-Fr RIJ, mm
access)
femoral LIJ
RFV,
28 Phynox
Vena Tech B. Braun 12.9 Fr No LFV,
mm sheet metal
RIJ
RFV,
Vena Tech LFV, 35 Phynox
B. Braun 9 Fr No
LP RIJ, mm wire
LIJ
RFV,
LFV,
RIJ,
Simon LIJ, 28
CR Bard 9 Fr No Nitinol wire
Nitinol RSV, mm
LSV,
RAV,
LAV
Yes
RFV, 28
Recovery CR Bard 9 Fr (jugular Nitinol wire
LFV mm
access)
7 Fr Yes RFV,
femoral, (jugular LFV 28
G2 CR Bard 10 Fr RIJ, Nitinol wire
jugular access) LIJ mm
RFV,
LFV,
Cordis RIJ, 30 Nitinol
TrapEase 8.5 Fr No
Endovascular LIJ, mm hypotube
RAV,
LAV
RFV,
LFV,
Yes
Cordis RIJ, 30 Nitinol
OptEase 8. 5 Fr (femoral
Endovascular LIJ, mm hypotube
access)
RAV,
LAV
FIGURE 24-2. Modified hook titanium Greenfield filter (Boston Scientific Inc).
FIGURE 24-3. Twelve-French stainless-steel Greenfield filter. This filter can be inserted
over a guide wire (Boston Scientific Inc).
FIGURE 24-4. Bird's Nest filter (Cook, Inc).
FIGURE 24-5. LGM Vena Tech filter (B. Braun Medical).
FIGURE 24-6. Vena Tech LP filter (B. Braun Medical).
FIGURE 24-7. Simon Nitinol filter (CR Bard).
TrapEase (Cordis Endovascular, Miami Lakes, FL)

The TrapEase filter was approved for use in the United States in 2000 (Fig. 24-8). The filter
has a hexagonal profile and is laser-cut from a single Nitinol hypotube. The filter has neither a
top nor a bottom because it has six longitudinal members that coalesce at each end of the
device. Clot trapping occurs at two levels and in two different areas: peripheral at the caudad
end and central at the cranial end. This approach is more analogous to the Bird's Nest than to
other devices that are rather cone shaped. For delivery through an 8.5-Fr outer diameter
sheath a pusher catheter is used to advance the filter. Final deployment is accomplished by
stabilizing the pusher catheter and withdrawing the sheath. Some shortening occurs as the filter
expands on delivery. The filter is approved for a maximal caval diameter of 30 mm. In a recent
study including 751 patients the TrapEase vena cava filter was effective in the prevention of
pulmonary embolism, with minimal complications (26).
FIGURE 24-8. TrapEase filter (Cordis Endovascular). This filter is perfectly symmetrical,
with identical caudal and cranial ends.
OPTIONAL VENA CAVA FILTERS (PERMANENT FILTERS

DESIGNED FOR RETRIEVAL) (TABLE 24-1)
Recovery Filter (CR Bard)
The Recovery filter was initially approved as a permanent device in November 2002. As the first
filter approved for retrieval in the United States in July of 2003, there was no change in
indications for use but addition of the wording Recovery filter may be removed according to the
instructions in the Section labeled: Optional Procedure for Filter Removal (FDA
510[k]#K031328). Approval was based in part on data from a series of 58 patients in Canada
in whom filter retrievals were performed from 2 to 161 days (mean, 60 days) (27). This study
demonstrated one filter migration (infrarenal to suprarenal), one filter fracture (arm), and one
removalrelated pulmonary embolism (asymptomatic) but otherwise no major complications or
recurrent thromboembolic disease. A more recent study evaluated retrieval of the Recovery
filter with dwell times beyond 180 days and demonstrated that retrieval was performed without
complications (28). However, this version of the Recovery filter is no longer commercially
available. The predicate device for the Recovery filter was the Simon Nitinol filter (CR Bard).
Both are constructed of Nitinol wire with bilevel filtration. The filter has six upper arms intended
to center the apex as well as trap thrombus and six anchoring legs arranged in a cone
configuration that also assist to trap thrombus. The maximum indicated caval diameter for this
filter is 28 mm. The feet of the device are flexible and straighten when traction is applied to the
filter in a cephalad direction. This enables the arms and legs of the filter to slip out of the wall of
the vena cava even after incorporation by neointima.
The successor of the Recovery filter is the G2 filter (CR Bard), which is currently approved as
a permanent filter in the United States and under study to obtain approval for retrieval
indication. The G2 filter utilizes the conical filter shape arranged into two offset layers to
effectively trap large and small emboli without compromising caval patency (Fig. 24-9). Secure
fixation within the IVC is achieved featuring a wider leg span and thicker fixation hooks to resist
filter migration with caval distension and higher pressures. The maximum indicated caval
diameter for this filter is 28 mm. For femoral filter delivery a 7-Fr delivery system is used. A
distinct jugular delivery system is also available. A specially designed pusher wire and
articulated arms promote a centered filter placement, even through tortuous anatomy.
For retrieval a dedicated grasping cone is required, which engages the filter apex at the junction
with the upper arms (Fig. 24-10). After the filter apex is secured with the cone, the filter is
pulled into the sheath with the cone. The sheath should not be advanced; this may cause
trauma to the wall of the vena cava, as the filter elements are peeled away rather than
extracted. Over-the-wire retrieval may be necessary when the filter apex is not readily engaged
with the cone due to filter tilting and angulation of the IVC. Attempted retrieval with a snare is
not recommended by the manufacturer due to the absence of a hook but can be accomplished
with a large sheath. At the time of writing of this chapter, there are no published reports on this
device.
Gnther Tulip Filter (Cook, Inc.)

The Gnther Tulip has the longest history worldwide as both a permanent filter and a
retrievable device, although it was
the second filter approved for retrieval in the United States (29,30) (Fig. 24-11). It was
introduced in Europe in 1992 and approved in the United States in 2000 as a permanent filter.
In late 2003 the U.S. Food and Drug Administration (FDA) finally approved labeling of the filter
for retrieval. Approval was based on clinical data demonstrating successful retrievals
between 2 and 20 days, but time limitations were not imposed by the FDA (31). The indications
for use of the filter were not changed. Retrieval of the filter was approved for patients who no
longer require a filter (FDA 510[k]#K032426).
FIGURE 24-9. G2 filter (CR Bard). The filter is retrieved by grasping it just below the head
of the filter (arrow) with a dedicated cone. The feet (arrowhead) are flexible and slide out
of the IVC wall.
FIGURE 24-10. Retrieval of a G2 filter. A: The filter is retrieved over a guide wire. B: The
cone is closed by advancing the sheath (arrowhead) until the grasping hooks are engaged
below the filter apex. The filter is removed by pulling the filter into the sheath while
maintaining the sheath in the same position.
FIGURE 24-11. Gunther Tulip filter (Cook, Inc). Apical hook (arrow) allows retrieval with a
snare from a jugular approach. Fixation anchors (arrowhead) are short and angled at 55
degrees.
FIGURE 24-12. Retrieval of the Gunther filter. A: Snare over filter hook (EN snare; inter. V,
Gainsville, FL). B: Snare closed on apex of hook (arrow). C: Sheath advanced (arrow) to
collapse filter.
The Gnther Tulip filter is a cone-shaped device made of Elgiloy wire featuring four primary
legs around which are thin wire petals that increase filtration efficiency. The caval fixation
anchors are designed to provide stability and to ensure retrievability. The filter is approved for
use in vena cavae up to 30 mm in diameter. A hook on the apex of the device allows snare
retrieval from a jugular approach (Fig. 24-12). The filter is detached from the IVC wall by
advancing a 7- to 10-Fr sheath over the filter to collapse the legs. The filter should not be pulled
into the sheath, as this may result in unintentional trauma to the wall of the IVC.
To date, the Gnther Tulip filter has the most supporting published data of the optional filters
regarding permanent use and retrieval (29,32, 33). Initial animal studies in dogs and swine
suggested that the window of retrievability was 14 to 16 days or less (35,26). The largest
published human series (90 patients) reported retrieval times ranging from 2 to 25 days, with a
mean of 9 days (30). There was only 1 failure in 52 attempted filter retrievals due to inability to
engage the apical hook. In the U.S. retrievability study (41 patients) the mean duration of
implantation was 11 days, with no retrieval failures (FDA 510[k]#K032426) (31). In clinical
practice 14 to 16 days is conservative, with retrieval reliably and safely achieved at 4 to 6
weeks at the author's institution. Anecdotal reports of retrievals of Gnther filters as long as
475 days postplacement exist, suggesting that the window of routine retrievability for this
device has yet to be determined (37, 38, 39). However, careful judgment and great care should
be exercised when attempting retrieval of filters that have been in place for extended periods of
time. An alternative strategy is to reposition the filter every 2 to 3 weeks to extend the period of
emplacement (33,40). The Gnther Tulip is the only optional device reported to have been
retrieved from the superior vena cava or a left-sided cava (34,41).
The next generation of the Gunther filter is the Celect filter (Fig. 24-13). The Celect filter can be
placed through a 7-Fr jugular or 8.5-Fr femoral system. Secondary struts engage the cava wall
first, centering the filter at deployment and throughout its use. Now with improved centering, the
Celect filter is proposed to be easy to retrieve at longer periods of time. This filter's current
regulatory status is approved for sale in Canada, pending approval in the United States (FDA)
and European Union (CE Mark).
OptEase Filter (Cordis Endovascular)

The OptEase was initially approved as a permanent filter by the FDA in late 2002, and for
retrieval in 2004 (FDA 510[k]#K034050) (Fig. 24-14). The manufacturer recommends a
retrievable period of 23 days. The instructions for use include no specific indications for
retrieval. Analogous to the TrapEase, the maximum caval diameter for this device is also 30
mm. There are two important features that distinguish the OptEase from the TrapEase. First,
the only fixation barbs are located at the cranial end of the filter body pointing in a cranial
direction, and there are no barbs oriented in a caudal direction. Therefore, unlike the TrapEase,
the filter is unidirectional and resistance to central migration is questionable if the filter is
inverted. Second, a hooklike appendage at the caudal apex of the filter allows retrieval with a
snare from the femoral approach. Usually a 30-cm, 7- to 10-Fr sheath is utilized (Fig. 24-15).
Recent studies showed that the OptEase filter can be safely retrieved in patients that require
temporary protection
against clinically significant PE or risk of pharmacologic therapy (42,43).
FIGURE 24-13. The Celect filter (Cook, Inc.) is the next generation of the Gnther filter.
Secondary struts engage the cava wall first, centering the filter at deployment and
throughout its use.
New models and designs of IVC filters are currently being developed or under investigation
(Fig. 24-16).
Convertible Vena Cava Filters

Per definition, convertible IVC filters are permanent filters that can be changed structurally after
implantation to no longer function as filters. However, no convertible filter is FDA approved yet.
Depending on the indications and clinical circumstances these filters can be placed with or
without the intension to be converted to a nonfiltration state (Fig. 24-17). Typically, convertible
vena cava filters maintain their position in the IVC with hooks, barbs, or radial pressure and
filter elements are subject to endothelial overgrowth. Usually a percutaneous imaging-guided
catheter-based procedure is sufficient to eliminate the filtering capacity. After conversion, either
parts or the entire filter remains in the patient's IVC but no longer provides protection from
pulmonary embolism. Filters that are not converted provide permanent filtration.
Temporary Vena Cava Filters

Temporary vena cava filters are characterized as devices that must be removed within a
specific time period (44). Typically these are tethered devices that have a catheter or wire
connecting the device to the venous insertion site. In most instances the tether exits the skin,
but it can also be buried subcutaneously. Currently these devices are not commercially available
in the United States.
FIGURE 24-14. OptEase filter (Cordis Endovascular). Based on the TrapEase Filter by the
same manufacturer, the caudal hook (arrow) and cranially oriented barbs (arrowhead)
allow removal with a snare from a femoral approach.
Biodegradable Vena Cava Filters
Biodegradable vena cava filters may be an innovative and potentially promising alternative
technology. These filters could provide optimal temporary protection against PE but dissolve
slowly after placement. Biodegradable filters could supersede the retrieval procedure, but first
their value needs to be evaluated scientifically.
INDICATIONS FOR FILTER PLACEMENT

The placement of optional filters with the aim to discontinue filtration through retrieval or
conversion should follow the same indications used for permanent vena cava filters (45). The
decision to use an optional filter and not a permanent filter should be based on the predictable
required duration of protection against clinically significant PE or risk of pharmacologic therapy.
FIGURE 24-15. OptEase filter retrieval. A: Snare (Amplatz Goose Neck; EV3, Plymouth,
MN) on filter hook (arrow). B: Filter partially pulled into sheath (arrow).
FIGURE 24-16. New filter models. A: Opinion LT filter (Rex Medical, Conshohocken, PA).
B: SafeFlo IVC filter (Rafael Medical Technologies, Caesarea, Israel).
FIGURE 24-17. Convertible IVC filter (B. Braun Medical, Bethlehem, PA) in nonconverted
(A) and converted (B) positions.
Principally, indications for all vena cava filters have been divided into absolute, relative, and
prophylactic categories (Table 24-2) (8,9,46, 47, 48, 49). Patients with absolute indications
have documented VTE, are at high risk of clinically significant PE, and have a contraindication
to or complication or failure of pharmacologic therapy (8,9,46, 47, 48, 49, 50). In some patients
with contraindications to or complications of anticoagulation, the period during which
anticoagulation therapy cannot be used may be temporary (51). In these situations optional
vena cava filters should be considered.
Patients with relative indications for vena cava filters have VTE and are considered to be at
sustained high risk of clinically significant PE despite primary therapy, at increased risk of
complications of anticoagulation, or noncompliant with medications. In general, the data
supporting the clinical value of filters for relative indications are sparser than those for absolute
indications. When the period of increased risk for clinically significant PE or complications of
anticoagulation is of a short duration in patients with relative indications for filters, optional filter
placement may be considered.
Patients with prophylactic indications for filters do not have VTE but are at increased risk for
clinically significant PE and unable to undergo primary prophylaxis. Although placement of IVC
filters for these indications is commonplace, the data supporting the practice are weak. The
one possible exception is filter placement in a setting of trauma in a patient deemed to be at
high risk (52,53). Additional specific clinical scenarios in which the use of prophylactic filters has
been reported, but is of unproven benefit, include critically ill patients with a history
of VTE and contraindication to anticoagulation, perioperative settings in patients with a history
of VTE and contraindication to anticoagulation, and patients undergoing bariatric surgery (54,
55, 56, 57, 58). When the period of increased risk for clinically significant PE is of short
duration, optional filters may be considered.
TABLE 24-2 SOCIETY OF INTERVENTIONAL RADIOLOGY INDICATIONS

FOR ALL VENA CAVA FILTERS (45)
Absolute indications (proven VTE)
1. Recurrent VTE (acute or chronic) despite adequate anticoagulation

2. Contraindication to anticoagulation
3. Complication of anticoagulation
4. Inability to achieve/maintain therapeutic anticoagulation
Relative indications (proven VTE)
1. Iliocaval DVT
2. Large, free-floating proximal DVT
3. Difficulty establishing therapeutic anticoagulation
4. Massive PE treated with thrombolysis/thrombectomy
5. Chronic PE treated with thromboendarterectomy
6. Thrombolysis for iliocaval DVT
7. VTE with limited cardiopulmonary reserve
8. Recurrent PE with filter in place
9. Poor compliance with anticoagulant medications
10. High risk of complication of anticoagulation (e. g., ataxia, frequent falls)
Prophylactic indications (no VTE, primary prophylaxis not feasible)a
1. Trauma patient with high risk of VTE

2. Surgical procedure in patient at high risk of VTE
3. Medical condition with high risk of VTE
a Primary prophylaxis not feasible as a result of high bleeding risk, inability to monitor
the patient for VTE, etc.
FIGURE 24-18. Left-sided inferior vena cava (IVC). A: Cavogram demonstrating left-sided
IVC (arrowhead). Patient has a feeding tube in place. B: Abdominal aorta is filled with
contrast (arrow). The pigtail catheter is in the IVC (arrowhead). C: An infrarenal IVC filter
was placed.
FILTER PLACEMENT
After determining the indication for and type of filter, a vena cavogram is performed to evaluate
caval patency, anatomy, and dimensions (Fig. 24-18). A measuring pigtail catheter can be used
to assess caval diameter, but unless imaging is obtained in multiple projections the accuracy of
the measurements with this technique may be uncertain. It is important to inject adequate
volumes of contrast (20-25 mL/second, for a total volume of 40-50 mL) at the confluence of the
iliac veins through a pigtail catheter. This will usually reflux a small amount of contrast into the
iliac veins and thus aid in the detection of a potentially duplicated vena cava, which occurs in
<1% of the population. The renal veins are identified as filling defects caused by unopacified
blood, although contrast may reflux into the origins in some patients. Frequently multiple renal
veins are present (Table 24-3). If the IVC anatomy is not well understood from the cavogram,
selection of individual branches should be made.
Alternative imaging techniques can be used for filter placement in patients that have
contraindications to iodinated contrast or radiation or who must remain in their hospital beds. If
a contrast allergy or renal insufficiency is present, either carbon dioxide gas or gadolinium can
be used as an alternative contrast agent (59,60). Furthermore, ultrasound (US)-guided
placement has been widely reported in the surgical literature (61, 62, 63, 64). However,
transabdominal US fails to provide adequate images of the IVC in up to 10% of patients, often
due to patient size, bowel gas, open abdominal wounds, and other technical issues. On the
other hand, intravascular US in experienced hands has proved to be highly accurate for the
depiction of vena cava anatomy (62,65, 66, 67). Accurate filter deployment is definitely
essential for adequate caval filtration (68).
First, the level of the orifice of the lowest renal vein is identified. Then the filter delivery sheath
is inserted into the IVC and the filter deployed with its apex just above or as close to the lower
lip of the lowest renal vein as possible. The hypothetical benefit of placement in this location is
to decrease the potential dead space above the filter should occlusion occur. The high blood
flow from the renal veins washing over the top of the filter is assumed to protect against
thrombus formation above the filter should occlusion occur. If there is insufficient space below
the renal veins due to a short IVC or the presence of thrombus, the filter can be placed in the
suprarenal segment of IVC between the renal and the hepatic veins (Table 24-4) (69). In a
patient with a duplicated IVC, a filter should be placed in
each IVC, or a single filter in the suprarenal location. When a large vena cava is present
(diameter >28-30 mm), the options are placement of a Vena Tech LP (for an IVC diameter 35
mm) or a Bird's Nest filter (for an IVC diameter 40 mm) in the infrarenal IVC, or simultaneous
filter placement in both common iliac veins. A repeat cavogram is performed through the
delivery sheath following filter deployment to document the final position of the device.
TABLE 24-3 ANATOMIC VARIANTS OF THE INFERIOR VENA CAVA AND

RENAL VEINS
Variant Incidence
Duplicated IVC 1.0%

Left-sided IVC 0.5%
Absent IVC 0.1%
Circumaortic left renal vein 7%
Retroaortic left renal vein 3%
Multiple right renal veins 28%
TABLE 24-4 INDICATIONS FOR SUPRARENAL IVC FILTER PLACEMENT
Suprarenal filter placement
1. Renal vein thrombosis

2. IVC thrombosis extending above the renal veins
3. Filter placement during pregnancy; suprarenal placement is also appropriate in
women of childbearing age.
4. Thrombus extending above previously placed infrarenal filter
5. Pulmonary embolism after gonadal vein thrombosis
6. Anatomic variants: duplicated IVC, low insertion of renal veins
Filter placement is safe in septic patients without fear of device infection (70). In pregnant
patients in their first trimester, filter placement can be performed from a jugular approach to
minimize radiation exposure. The classic teaching is to place the filter in the suprarenal location
in pregnant women or women of childbearing age, although there is no objective evidence
supporting this practice. Infrequently, patients with upper extremity venous thrombosis require
placement of a filter in the superior vena cava (SVC) (71). The filter should be oriented
appropriately toward the heart, with the anchoring feet just below the confluence of the right
and left brachiocephalic veins (Fig. 24-19). From the author's point of view the TrapEase,
OptEase, G2, and Bird's Nest should not be used in this location, but there are no objective
data that support this belief.
INDICATIONS FOR FILTER RETRIEVAL

The current guidelines for removal of retrievable filters were recently reported by the Society of
Interventional Radiology Multidisciplinary Consensus Conference and endorsed by the American
Venous Forum (45). Since the sole purpose and function of a vena cava filter are to prevent
clinically significant PE, the basic clinical indication for filter retrieval is an acceptably low risk of
PE. Typically this is the case when then patient is receiving satisfactory anticoagulation
treatment or has passed the period of risk for VTE (50,72, 73, 74, 75, 76, 77). At this point the
presumed risks of the filter in place must be weighted against the estimated future risk of
recurrent PE. At present the balance of risks cannot be quantified due to a lack of clinical data
and the complexity of real clinical situations and, therefore, remains a matter of physician
judgment. Long-term anticoagulation is associated with a small but definable incidence of
complications, which are usually hemorrhagic (51). To avoid lifelong anticoagulation after the
patient no longer requires treatment of VTE, filter retrieval may be warranted. The life
expectancy of the patient should be long enough that the presumed benefits of filter retrieval
can be realized (Table 24-5).
FIGURE 24-19. Filter placed in the superior vena cava for upper extremity deep vein
thrombosis. The apex of the filter (arrowhead) is oriented toward the heart. A central
venous access line (arrow) is present.
FILTER OUTCOMES
The outcomes of IVC filters are summarized in Table 24-6 (7, 8, 9,78, 79, 80). Reporting
standards for permanent vena cava filters have been developed by a multidisciplinary group
(46). Recently, reporting standards for temporary and retrievable/optional filters were
supplemented (81). At present, only sparse reliable data on the long-term efficacy and safety
of IVC filters are available. There is only one randomized prospective study reporting the
outcomes of IVC filters in patients with proximal lower extremity VTE at 2 and 8 years (12,13).
That study demonstrated that the beneficial effect of IVC filters preventing PE was
counterbalanced by an increase in recurrent VTE without any difference in mortality. Of interest,
IVC filters did not increase the risk of postthrombotic syndrome.
However, due to a lack of adequate prospective controlled studies, determination of acceptable
short- and long-term outcomes of filters is still based on expert opinion. In the purest sense,
there is little proof to support the contention that IVC filters reduce death due to pulmonary
embolism, despite the widespread belief that this is indeed true. This overall uncertainty about
the long-term outcomes of filters is part of the rationale for optional or removable vena cava
filters.
The primary objective of vena cava filters is to prevent PE. When a patient with a filter
experiences a suspected recurrent PE, the first step is to document the event with imaging or
some other conclusive evidence. The next step is to
determine whether the patient can be treated with anticoagulation. Patients that can be
anticoagulated should be treated with a full course of therapy. Patients that cannot be
anticoagulated should undergo evaluation for the origin of the PE. The discovery of new lower
extremity deep vein thrombosis (DVT), thrombus trapped in the filter, or thrombus extending
above the filter all imply filter failure. A second filter should be placed in this situation, usually
inferior to the original filter unless thrombus extends above the first device or the IVC is
thrombosed. Under these circumstances the filter should be placed above the first, typically in
the suprarenal IVC.
TABLE 24-5 SAMPLE PROTOCOL FOR CLINICAL IMPLEMENTATION OF

RETRIEVABLE FILTERS
1. Indications
Patients at risk for thromboembolic disease or its complications (DVT, PE)

a. who require interruption of the IVC on a temporary basis and who have IVC
dimensions appropriate for available retrievable filters. Examples include:
i. Multiple trauma (head, pelvic fractures, nonquadriplegic spinal injury)

ii. Patients with documented current or past DVT/PE who must
temporarily stop anticoagulation therapy, for example, prior to surgery
Patients undergoing surgical procedures with a high risk of DVT/PE in

iii.
the postoperative period
Patients with massive PE undergoing initiation of

iv.
anticoagulation/thrombolysis
2. Contraindications
All retrievable filters are approved for use as permanent filters. However, the
a.
following patients are usually not candidates for filter removal:
Failure of anticoagulation (for example, recurrent or progressive

i.
DVT/PE while adequately anticoagulated)
ii. Quadriplegia
iii. Pulmonary hypertension, especially when due to chronic PE
iv. Life expectancy <6 months
v. Noncompliance due to choice or dementia
vi. Multiple severe chronic medical or surgical diseases
3. Conditions for retrieval
a. All patients:
i. Permanent filter not indicated
b. If no prior diagnosis of DVT or PE:
i. Obtain lower extremity ultrasound study to exclude DVT.
Patient must be on DVT/PE prophylaxis (low molecular weight heparin,

ii.
coumadin) or no longer at risk of DVT/PE (returned to normal activity).
iii. Patient agrees to have filter removed.
c. Prior diagnosis of DVT/PE:
Patient is stable on first-line therapy for DVT/PE (full anticoagulation).

i. With prior DVT, consider US to exclude progression of DVT despite
anticoagulation.
ii. Patient agrees to have filter removed.
4. Removal procedure
a. Do not interrupt anticoagulation therapy.
b. Obtain creatinine, CBC with platelets, and PTT/INR.
c. If patient on coumadin:
i. Removal postponed for INR >3.5 or <2.0
d. Spot film of abdomen to document filter position
e. Venacavogram to exclude trapped thrombus:
i. Operator makes determination regarding removal if thrombus present.
f. Venacavogram postremoval
g. Patient observed postremoval
i. 2 hours if jugular approach
ii. 4 hours if femoral approach

TABLE 24-6 OUTCOMES OF INFERIOR VENA CAVA FILTERS
Recurrent pulmonary embolism 5%
Symptomatic complete IVC occlusion 5%
Symptomatic insertion-site thrombosis 2%
Major filter migration (to heart, lungs, iliac veins) <1%
Filter fracture with clinical consequences <1%
Symptomatic perforation adjacent structures <1%
Recurrent DVT 20%
When PE recurs in a patient with an IVC filter but no obvious lower extremity venous
thrombosis, other sources of emboli should be considered. These include the internal iliac,
gonadal, renal, and upper extremity veins. A suprarenal filter is required for the management of
emboli from the renal and gonadal veins in a patient that cannot be anticoagulated. Placement
of a filter in the SVC may prevent further PE from upper extremity DVT.
Occlusion of vena cava filters may be caused by trapping of a massive embolus of in situ
formation of thrombus (16,17,82). The majority of these cases are believed to be
asymptomatic. Symptomatic occlusion of a filter can be treated with anticoagulation or
thrombolysis if the patient no longer has contraindications to these therapies. Conservative
measures such as elevation of the extremities and compression stockings are also useful.
Rarely, thrombosis of the IVC or iliofemoral veins (unilateral or bilateral) after filter placement
results in arterial ischemia (phlegmasia cerulea dolens) (83). This typically occurs soon after
initial filter placement in a hypercoagulable patient. Surgical venous thrombectomy and even
amputation may be necessary, but the mortality rate is generally high.
Recurrent DVT with subsequent symptomatic chronic venous insufficiency is considered one of
the major adverse outcomes of vena cava filters (80). Thrombosis at the insertion site is one of
the proposed etiologies of DVT after filter placement, but the majority of these are nonocclusive
and self-limited (84,85). The routine use of jugular vein insertion sites would eliminate the
incidence of this complication. The only prospective randomized trial comparing the treatment of
VTE with anticoagulation plus filters versus anticoagulation alone showed a significant increase
in recurrent DVT at 2 years in patients with filters, without a significant survival benefit (12).
This study also showed a significant early (12-day) survival benefit with filters that disappeared
by 2 years. Most prior retrospective studies had concluded that the primary determinant of
chronic venous insufficiency after filter placement was the degree of preexisting DVT at the
time of filter placement (86,87).
The long-term outcomes (i.e., years) of SVC filters are not known. The majority of patients
reported in the literature with filters in this location have been extremely ill with short life
expectancies.
SUMMARY
Vena cava filters are important in the management of VTE but remain poorly understood. The
development of optional and temporary filters may address some of the long-term concerns
about vena cava filters but will not diminish the need for sound data on filter outcomes.
Individual physician judgment is therefore critical in the application of these devices and
subsequent patient management.
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> Table of Contents > Section III - Vascular Interventions > Part B: - Systemic Venous Interventions > Chapter 25 - Varicose
Veins
Chapter 25
Varicose Veins
Robert J. Min
Neil M. Khilnani
PATHOPHYSIOLOGY AND EPIDEMIOLOGY

Lower extremity chronic venous insufficiency (CVI) is caused by venous hypertension most
often resulting from increased hydrostatic forces due to primary valvular insufficiency (1,2).
Less commonly, venous obstruction, muscular pump failure, and congenital anomalies are the
initiating causes. Some element of superficial venous insufficiency (SVI) is associated with the
vast majority of patients with CVI and significant reflux in the great saphenous vein (GSV) or in
one of its primary tributaries is seen in 70% to 80% of patients. Small saphenous vein (SSV)
reflux is found in 10% to 20% and other sources of non-saphenous reflux are identified in 10%
to 15% of patients (2,3).
Venous insufficiency is extraordinarily common, with estimates of up to 25% of women and
10% of men suffering from some form of SVI (4). Most patients with SVI have leg symptoms,
which include aching, fatigue, throbbing, heaviness, and night cramps. Severe cases can lead to
skin damage resulting from chronic venous hypertension, including eczema, edema,
hyperpigmentation, lipodermatosclerosis, and ulceration. Family history is the primary risk
factor for developing SVI, with 90% of people developing varicose veins if both parents suffer
from the disease, 25% of males and 62% of females when one parent is affected, and 20% of
cases when neither parent is affected (5). Multiparity and occupations requiring prolonged
standing can increase the risk of developing varicose veins in those genetically predisposed or
can worsen existing cases of SVI (6).
ANATOMY
The superficial venous system of the lower extremity is composed of innumerable subcutaneous
collecting veins, the saphenous trunks, and their tributaries. The GSV begins on the ventral and
medial portion of the foot, runs anterior to the medial malleolus, and ascends the medial aspect
of the calf and thigh to ultimately join the femoral vein at the fossa ovale via the saphenofemoral
junction (SFJ). The saphenous compartment, bounded superficially by the saphenous fascia
and deeply by the muscular fascia, contains the saphenous veins, accompanying arteries, and
nerves (7). The GSV travels in close proximity to the saphenous nerve (sensory) from the ankle
to 6 cm below the knee.
In the thigh, the anterior and posterior circumflex veins run obliquely in the anterior and posterior
thigh, respectively (7). The anterior thigh circumflex vein can originate from the lateral venous
system, while the posterior circumflex vein may originate from the cranial extension of the SSV.
The external pudendal, superficial circumflex iliac, and superficial epigastric veins are other
named tributaries (7) and are illustrated in Fig. 25-1. The anterior accessory GSV courses
parallel and anterior to the main trunk of the GSV in both the leg and the thigh. An incompetent
anterior accessory GSV is frequently an unrecognized underlying cause for anterior thigh
varicose veins (7). The posterior accessory GSV indicates any venous segment that travels
parallel and posterior to the main trunk of the GSV. The portion of the posterior accessory GSV
in the leg is the current term for the previously referred to Leonardo's vein or posterior arch vein
(7). A vein that runs parallel to the GSV but more superficial to the saphenous fascia is
described as a superficial accessory GSV. Like the anterior accessory GSV, the posterior
accessory GSV and other tributaries can be the underlying cause of significant varicose veins
alone or in combination with GSV reflux.
Beginning on the lateral aspect of the foot the SSV ascends posterior to the lateral malleolus
and then up the midline of the calf, between the same fascial planes as the GSV. The SSV runs
adjacent to the sural nerve (sensory) from the foot to just below the popliteal crease. In about
two thirds of cases, the SSV drains into the popliteal vein at or just above the knee. In about
one third, it has a cephalad extension with or without a saphenopopliteal junction (SPJ) to
ultimately drain into a posterior thigh perforating vein or into the posterior thigh circumflex vein
via the vein of Giacomini.
Perforators course obliquely through the deep fascia connecting the superficial system with the
sinusoidal, tibial, popliteal, and femoral veins. Unidirectional valves within the perforating veins
direct flow from the superficial to the deep veins.
CLINICAL EXAMINATION
Medical providers often underestimate the complexity of disorders of the superficial venous
system and the importance of a proper history and physical examination. Information gathered
should include the duration and evolution of the problem, presence and severity of symptoms,
prior treatments, and possibility of prior deep venous thrombosis (DVT). Clinical evaluation of
lower extremity venous insufficiency should be performed in the standing position, preferably on
a platform, and involve careful inspection, palpation, and percussion. Examination should include
not only the legs, but also the lower abdomen and pubic area.
DUPLEX ULTRASOUND EVALUATION

Clinical examination will suffice for the majority of patients with only telangiectasia but those
with varicose veins should be further evaluated with duplex ultrasound (DUS) (8,9). The goal of
the DUS evaluation is to map out all the incompetent venous pathways responsible for the
patient's condition, including the primary or highest points of reflux and to examine
for the presence of obstruction (8). Such a map is necessary to determine the best treatment
plan based on the findings.
FIGURE 25-1. The great saphenous vein and its major named tributaries.
Great Saphenous Vein
Unlike evaluation for DVT, DUS examination for SVI is performed with the patient upright. The
leg being studied is flexed and turned slightly outward as seen is Fig. 25-2. Evaluation is
performed in a systematic manner, most commonly beginning at the groin and proceeding
peripherally. The entire length of the GSV is examined in axial projection. Vein diameter is
measured and the major tributaries are followed and examined. Varicose tributaries are noted
and followed to determine the associated underlying sources of reflux.
The SFJ is assessed for the presence of reflux in both longitudinal and transverse views. Color
Doppler can rapidly facilitate the identification of reflux by moving the probe along the vein while
manually compressing and releasing peripheral vein segments. Reflux is confirmed by pulsed
wave Doppler using similar techniques of distal compression and release.
FIGURE 25-2. Upright patient positioning (leg flexed and slightly rotated outward) during
DUS examination of the right GSV for reflux.
Perforating Veins
Perforating veins associated with the GSV in the thigh and the posterior accessory GSV below
the knee are studied similarly. Axial and oblique scanning planes are most helpful when
evaluating perforators. Both perforator vein size and valve competency should be noted.
Small Saphenous Vein

With the patient facing away, the knee is slightly flexed to relax the popliteal region and prevent
venous compression by adjacent tissues. The SSV is identified and examined in its entirety in
the axial plane. Drainage of the SSV into the deep venous system is determined. The size,
competency, connection(s) with the deep veins, and relationship to posterior calf varicose veins
are evaluated in a manner similar to that used for the GSV. Perforating veins connecting the
SSV with the venous sinusoids are noted, including the level of inflow and competence of the
gastrocnemial veins.
TREATMENT
Medical treatment may be contemplated when symptoms from CVI persist despite conservative
methods such as graduated compression stockings and exercise. Other indications may include
treatment or prevention of complications arising from chronic venous hypertension such as
bleeding, superficial thrombophlebitis, and damage to the skin. Treatment
usually starts with elimination of all underlying sources of truncal reflux. Techniques available to
accomplish this include surgical removal, endovenous laser treatment, endovenous
radiofrequency ablation, or US-guided sclerotherapy with liquid or foamed sclerosants.
COMPRESSION SCLEROTHERAPY
Sclerosants
Although many sclerosing agents have been used, only a few are appropriate choices for the
safe treatment of varicose veins and telangiectasias. The most commonly used sclerosants are
discussed below.
Sodium morrhuate and ethanolamine oleate are approved by the U.S. Federal Drug
Administration (FDA) for sclerotherapy but unacceptably high anaphylaxis risks make them poor
choices for treatment of varicose veins and telangiectasias (10).
Hypertonic saline is not FDA-approved for sclerotherapy of leg veins but is often used for this
purpose in the United States. The concentration varies from 11.7% or 23.4%, depending on
vein size and responsiveness. It is widely available, inexpensive, and rarely allergenic; however,
hypertonic saline causes burning pain, has a high risk of skin ulceration, and is quickly diluted,
limiting the size of vein that can be treated.
Dextrose and hypertonic saline (25% dextrose, 10% sodium chloride) are produced in Canada
under the trade name Sclerodex and are not FDA-approved in the United States. Its effects are
similar to those of hypertonic saline, but given its lower saline concentration, Sclerodex is less
painful and has a lower risk of skin necrosis. It is used mainly for treatment of telangiectasias
and reticular veins.
Polidocanol (hydroxypolyethoxydodecane) is not FDA-approved in the United States but is the
most commonly used sclerosing agent in Europe. It is has an excellent safety profile, with low
risk of extravasation necrosis or allergic reaction, and is painless upon injection. Polidocanol is
used at concentrations of 0.25% to 4% to treat the whole range of veins from telangiectasias to
incompetent saphenous veins.
Sodium tetradecyl sulfate (STS) is approved by the FDA and is the most widely used sclerosing
agent in the United States to treat telangiectasias and varicose veins. It has a long history as a
safe sclerosant and is effectively used to treat the whole spectrum of incompetent veins in
concentrations of 0.1% to 3%.
General Principles
Although proper use of any of the sclerosants above may yield an acceptable result, treatment
efficacy will be maximized and complications minimized by following a few basic principles. In
general, the concentration of sclerosant is dependent on both the type and the diameter of vein
to be treated. It is best to start with the minimum sclerosant strength necessary to achieve
effective sclerosis since excessive damage may result when solutions too high in concentration
are used. Injections usually proceed from central to peripheral and from larger to smaller veins.
Although reflux can be present in a vein without an apparent underlying source, visible veins are
often fed by other veins. Telangiectasias may be associated with refluxing reticular veins;
bulging varicose veins can be due to incompetent saphenous veins, perforator veins, or truncal
tributaries. These underlying sources will need to be addressed to achieve the best results.
Patient Selection
In addition to known allergy to the sclerosant, other relative contraindications to compression
sclerotherapy include patients with known or suspected risk factors for DVT such as prior DVT
or pulmonary embolus, family history of hypercoagulability, air or other long-distance travel,
prolonged bed rest, and inability to ambulate. Others who should not be treated with
sclerotherapy are pregnant or nursing women, people with significant systemic illness, patients
with nonpalpable pedal pulses, and those with unrealistic expectations. Although deep venous
reflux is not a contraindication, sclerotherapy of superficial varicose veins should be avoided in
patients with acute deep venous obstruction.
Technique
Sclerotherapy is usually performed with the patient laying down, which decreases the risk of a
vasovagal reaction and allows injection into a relatively empty vein, minimizing dilution by blood
and maximizing contact with endothelium. The overlying skin is wiped with isopropyl alcohol and
the vein is entered with either a 27- or a 30-gauge needle attached to a 3-mL syringe.
Cannulation should be brisk with the needle bevel facing up. Prior to injecting veins larger than
telangiectasias, a small amount of blood should be aspirated into the needle hub to verify
intravenous placement. In general, larger veins require higher concentrations and greater
volumes of sclerosant injected every 3 to 5 cm for effective sclerosis. Telangiectasias require
no more than a few drops of a mild sclerosant (e.g., 0.2% STS), reticular veins are injected
with a few tenths of a milliliter of a slightly stronger solution (e.g., 0.3% to 0.5% STS), and
bulging varicose veins may be treated with 0.25 to 1 mL of a higher-concentration sclerosant
(e.g., 0.5% to 1% STS). Minimal pressure is used for injection of sclerosant, which should be
painless when using Polidocanol or STS.
Postsclerotherapy Care
Although it is generally agreed that some form of graduated compression following
sclerotherapy is beneficial, the optimal protocol has been debated. Following sclerotherapy of
telangiectasias and small varicose veins, most physicians advocate wearing mild graduated
compression (15 to 20 or 20 to 30 mm Hg) for at least 5 to 7 days. In general, treatment of
larger varicose veins requires more graduated compression (20 to 30 or 30 to 40 mm Hg) for
longer periods of time posttreatment. In theory, graduated compression improves treatment
efficacy, minimizes adverse reactions such as trapped blood with resultant hyperpigmentation,
and decreases the risk of DVT. Ambulation should be encouraged immediately following
sclerotherapy to lessen risks further. Patients should avoid vigorous gym workouts, excessive
sun, hot baths, or air travel for the first week following treatment.
Patients are seen for follow-up 2 to 4 weeks after injections. Previously treated areas are
examined and areas of intravascular hematoma or trapped blood are expressed through an
18- or 25-gauge needle puncture. Although trapped blood is eventually absorbed over months,
removing it in a timely fashion will minimize hyperpigmentation from hemosiderin staining of the
overlying skin. Additionally, these areas of trapped blood are often tender and patients will
experience immediate relief following removal. Additional sclerotherapy treatment can be
performed at 4- to 6-week intervals, which allows adequate time for inflammation to subside
and the benefits of prior treatment to be realized. Areas treated, amount injected,
concentration used, and locations of trapped blood removed are recorded for each treatment
session and adjustments are made at follow-up based on treatment response.
Ultrasound-Guided Sclerotherapy
DUS can be used to guide an injection of sclerosant into a refluxing non-surface vein which is
the underlying cause for the visible varicosities. US-guided sclerotherapy of the saphenous vein
may be an alternative or complementary technique to surgery, endovenous laser ablation, and
radiofrequency ablation. It can also be used to treat an incompetent truncal tributary,
neovascularization following surgery, or other significant source of reflux in the superficial
venous system. Sclerosant can be delivered via direct needle puncture under DUS guidance or
using transcatheter techniques (11).
Foam Sclerotherapy
Originally introduced decades ago, treatment of varicose veins with sclerosant foam has gained
renewed interest in recent years. Various methods of producing and delivering foam with
detergent sclerosants have been described in the literature (12, 13, 14, 15). Foaming the
sclerosant increases the strength of the agent by displacing blood and maximizing contact
between sclerosant and endothelium. Increased efficacy of treatment of large incompetent
veins with foam sclerotherapy compared to conventional liquid sclerotherapy has been
suggested by a few nonrandomized studies (16, 17, 18). Unfortunately, displacing blood and
remaining in the vein longer appear to increase not only the sclerosant strength but also the
incidence of adverse reactions. DVT, visual disturbances, and even ischemic stroke have been
reported after foam injection sclerotherapy of varicose veins in a patient with a patent foramen
ovale (19). The long-term efficacy of foam sclerotherapy has yet to be determined.
Adverse Reactions and Complications

Hyperpigmentation following sclerotherapy is the most common side effect, seen in 10% to
20% of patients following sclerotherapy. Hemosiderin deposition is believed to be the cause of
the brownish discoloration of the overlying skin. In the vast majority of cases, the darkening is
temporary and resolves within months but it may occasionally last significantly longer (20).
Although it may result even with meticulous technique, using too much sclerosant, using
sclerosant that is too strong, and leaving underlying sources of reflux untreated will increase the
amount and severity of hyperpigmentation. Removal of trapped blood following sclerotherapy
reduces the hemosiderin load and minimizes skin darkening. If hyperpigmentation does occur,
management should include reassurance, protection from excessive sun, and time.
Telangiectatic matting, tiny new red blood vessels appearing in an area of treatment, is another
possible adverse reaction to sclerotherapy. Fortunately, like hyperpigmentation, telangiectatic
matting is most often temporary. If matting persists for longer than a few months, an untreated
underlying source of reflux should be investigated and addressed. As with most side effects,
the best treatment is avoidance of the complication by using meticulous technique. In particular,
using the minimum effective sclerosant strength and injecting small volumes under low pressure
are important preventive measures (21). Obesity and exogenous hormones seem to increase
the risk of telangiectatic matting (22,23).
Skin ulceration may result from extraluminal injection, extravasation of sclerosant, or intra-
arterial delivery. Although any sclerosant can cause breakdown of the skin if it is too strong or
improperly injected, certain sclerosing agents such as hypertonic saline pose greater risks of
causing ulceration. Other factors that increase the incidence of this side effect are practitioners
lacking adequate training or experience and certain anatomic injection dangers zones such as
the ankle.
Although allergy to the most widely used sclerosing agents is uncommon, these reactions can
occur and providers performing sclerotherapy should be prepared to treat urticaria, rash, or
anaphylaxis. Fortunately, intra-arterial injection is a rare complication but has been reported,
and extreme care must be exercised when performing sclerotherapy in the medial malleolar,
saphenofemoral, and saphenopopliteal regions.
ENDOVENOUS LASER ABLATION

In 1999, Dr. Bon first reported on delivery of endoluminal laser energy (24). Since then, a
method for treating the entire incompetent GSV segment has been described by Min and
Navarro (25, 26, 27). Endovenous laser treatment, which received FDA approval in January
2002, creates nonthrombotic vein occlusion by delivery of laser energy directly into the vein
walls. Lasers with wavelengths of 810, 940, 980, and 1,320 nm have all been used with
reported success. Maximal contact between the laser fiber and the vein wall is necessary to
cause sufficient damage to the vein, resulting in wall thickening with eventual contraction and
fibrosis of the vein. Over the past 5 years, reports of impressive clinical success and low
complication rates have made endovenous laser treatment the treatment of choice for
eliminating reflux in incompetent truncal veins.
Patient Selection
The indications for ablation of incompetent truncal veins are identical to those for surgical
ligation and stripping. Many of the exclusion criteria described for sclerotherapy are also
relative contraindications for endovenous laser, including nonpalpable pedal pulses, inability to
ambulate, DVT, general poor health, and women who are pregnant or nursing. An additional
relative contraindication to all catheter-based endovenous ablation techniques are
nontraversable vein segments due to either thrombosis or extreme tortuosity. Fortunately, this is
an uncommon finding and should be recognized on pretreatment venous duplex US mapping.
Technique
Prior to treatment, the abnormal venous pathways are mapped using US guidance and the
veins to be treated are marked on the overlying skin with the patient standing. Additional
important landmarks such as junctions, aneurysmal segments, and areas of significant blood
flow from tributaries or perforators should be marked on the skin.
The patient is placed horizontal on the table, allowing full access to the treated segments. In
general, patients being treated for GSV reflux are placed supine or in the oblique position with
the hip slightly turned to expose the course of the GSV. When the SSV is the target, patients
are placed prone with their feet hanging off of the end of the table in order to relax the calf
muscles and popliteal fossa. Treating an incompetent vein of Giacomini or multiple sources of
venous reflux may require multiple repositions and reprepping.
In almost all cases the target vein is entered directly or access is gained via one of its principal
tributaries. Tributary veins are more prone to venospasm and may be more difficult to access.
Entry via a tributary should only be attempted if the vein is
relatively straight and of sufficient diameter. Generally the vein is punctured at or just peripheral
to the lowest level of truncal reflux as determined by DUS. At this point, the vein diameter
dramatically decreases just after it gives off a refluxing tributary and regains its competence. In
many cases, GSV incompetence can occur segmentally. The reflux can completely spill out into
a tributary vein, which then re-enters the GSV at a lower level. In such a case, the lowest
incompetent vein segment should be accessed and all refluxing vein segments ablated via one
puncture or more than one puncture if necessary.
The target vein is entered with either a 19- or 21-gauge needle using real-time US guidance
and single-wall technique. Utilizing reverse Trendelenberg positioning and keeping the
procedure room warm until access is obtained will help minimize shrinkage. Other ancillary
procedures advocated by some practitioners to maximize vein size include a heating pad and a
small amount of nitroglycerin paste at the access point. Non-GSV segments are particularly
prone to venospasm and particular care must be taken when accessing a tributary vein
segment or a truncal vein such as the anterior accessory GSV, SSV, or thigh circumflex vein.
A 5-Fr vascular sheath is inserted over a guide wire into the vein and passed through the entire
abnormal segment and into a more central vein. A bare-tipped laser fiber is inserted into the
sheath. The sheath is then pulled back, exposing the tip of the fiber, and the fiber is locked in
place. Using US guidance, the sheath and fiber are withdrawn as a unit out of the deep veins
and positioned within the superficial venous system at the junction as shown in Fig. 25-3. The
fiber is left in this position during tumescent anesthesia administration and repositioned just prior
to delivery of laser energy. Confirmation of the position can be made by direct visualization of
the red aiming beam through the skin.
One of the most important steps in the procedure is correct delivery of perivenous tumescent
anesthesia. Tumescent anesthesia is a form of local anesthesia delivery that utilizes large
volumes of dilute anesthetic solutions, permitting anesthesia of large areas. Proper use of
tumescent anesthesia should make endovenous laser painless, without the need for intravenous
sedation or general anesthesia. In fact, it can be argued that sedation adds risk to endovenous
laser treatment by blunting patient feedback during the procedure as well as delaying
immediate ambulation afterward.
In addition to making the procedure painless, tumescent anesthesia is also used to maximize
safety and efficacy of endovenous laser treatment. Although venospasm may occur in portions
of some accessed veins, proper delivery of tumescent fluid into the perivenous space will
ensure compression of the vein around the laser fiber. The goal of US-guided delivery of
tumescent anesthesia is to achieve circumferential contact between the vein walls and the laser
fiber tip. This will allow adequate transfer of laser energy to the target vein walls, resulting in
vein wall damage and subsequent fibrosis. Inadequate vein emptying, with too much blood
remaining in the vein, will lead to nontarget heating. In the latter case, if occlusion occurs, it will
be the result of thrombosis with inevitable vessel recanalization.
FIGURE 25-3. Longitudinal DUS image of the SFJ (patient's head is to the left) during laser
fiber positioning. The fiber and sheath are pulled out of the femoral vein (FV) and
positioned within the GSV.
The surrounding cuff of tumescent fluid also serves as a protective barrier to prevent heating of
nontarget tissues, including skin, nerves, arteries, and the deep veins. Delivery of tumescent
fluid in the proper plane can only be achieved with DUS guidance. This fluid is used to separate
adjacent nontarget structures from the target vein. Some practitioners advocate injecting the
fluid blindly or using highly pressurized devices to administer the tumescent fluid as is often
done prior to liposuction. Although perhaps quicker, such systems offer less control compared
to hand injection. For this reason, we prefer to deliver the tumescent anesthesia using hand
pressure and a 1.5-in., 25-gauge needle attached to a 20-mL syringe. For right-handed
operators, the tumescent fluid is given from distal to proximal. Skin punctures are required
every 3 to 5 cm until the proper perivenous tissue plane is located. Once this occurs, fluid will
track more easily up and around the target vein and greater distances can be covered with
each needle puncture.
To treat a 45-cm segment of vein, approximately 100 to 150 mL of 0.1% lidocaine neutralized
with sodium bicarbonate may be required. This mixture can be made by diluting 50 mL of 1%
lidocaine in 450 mL of normal saline and adding 5 to 10 mL of 8.4% sodium bicarbonate. If it is
anticipated that larger volumes of tumescent anesthesia will be necessary, a concentration of
0.05% lidocaine can be used effectively. These amounts of lidocaine are well within the safe
doses of 4.5 mg/kg without epinephrine and 7 mg/kg with epinephrine. Although many
practitioners choose to use lidocaine with epinephrine to maximize venospasm and minimize
bruising, we achieve adequate and complete vein emptying utilizing plain lidocaine and avoid the
risk of toxicity related to epinephrine.
Following tumescent anesthesia administration, US is used to check for adequacy. A centimeter
halo of fluid surrounding the target vein or separating the vein from the overlying skin has been
found to be sufficient. Proper delivery of tumescent fluid is especially critical to procedural
safety when performing endovenous laser in certain locations such as the SSV near the SPJ or
the GSV below the knee due to the close proximity of nerves or arterial branches. Checking
with color Doppler following tumescent anesthesia delivery can be useful when assessing
adequacy of separation of the SSV from sural artery branches as shown in Fig. 25-4.
Placing the patient into Trendelenberg position (head down) either before or after delivery of
tumescent anesthesia will facilitate vein emptying. Proper tumescent anesthesia and
Trendelenberg position will usually result in sufficient laser fiber and vein wall contact. If
additional vein emptying is necessary, other maneuvers can be used including raising the leg,
compressing manually, applying suction to the sheath, and cooling the room to induce
vasospasm. Since the laser fiber can move during tumescent anesthesia administration, the
laser fiber is repositioned prior to delivery of laser energy. For the GSV, the fiber tip is
positioned at or below a competent superficial epigastric vein or 5 to 10 mm peripheral to the
SFJ. When treating the SSV, seeing the fiber tip can be difficult due to the acute angle taken by
the SSV as it dives to join the popliteal vein. Following delivery of tumescent anesthesia with
flattening of this angle, the laser fiber tip may be more easily visualized with US. Accurate
preprocedure marking of the SPJ is important and, when
used with the red aiming beam, will enable precise positioning of the laser fiber. Even in obese
patients, this red light can be seen, although dimming the room lights may be necessary.
Optimally, the laser fiber tip is placed 10 to 15 mm peripheral to the SPJ where the SSV turns
parallel to the skin just below the popliteal fossa.
FIGURE 25-4. Transaxial color Doppler image of the SSV demonstrating separation of
surrounding arterial branches from the SSV with tumescent anesthesia fluid, protecting
these nontarget tissues from heat damage. (See the color insert.)
The vascular sheath and fiber are withdrawn together during laser activation (Fig. 25-5). In our
practice, using the 810-nm diode laser (Diomed Holdings Inc., Andover, MA) laser energy is
delivered using 14 W in continuous mode. The amount of energy necessary to effect reliable
vein ablation seems to be an average of 70 J/cm throughout the treated segment (28). The
average pullback rate to accomplish this is 2 mm/second. Although automatic catheter pullback
devices are available, these are an unnecessary expense. Most manufacturers of endovenous
laser ablations kits now provide marked vascular sheaths. Used with the elapsed time display
of the laser system, it is simple to determine the pullback rate. This combination permits
accurate and standardized delivered of laser energy. Simple manual withdrawal also allows
laser energy delivery to be customized to the particular vein segment being treated, which
enhances treatment efficacy and safety. For example, when treating the GSV, higher laser
energies are delivered to the most central portion of the vein, with the first 10 to 15 cm of the
vein treated with 140 J/cm, which is achieved by withdrawing the laser fiber at a rate of 1
mm/second. In general, this segment of the GSV is the most prone to treatment failure and is
the least susceptible to venospasm. Thus, it is necessary to deliver proportionately larger
amounts of tumescent anesthesia and higher laser energies to adequately treat this important
vein segment. Higher laser energies are also delivered in regions of blood inflow such as near
junctions with incompetent tributaries or refluxing perforators. When treating vein segments
close to the skin, the SSV near the SPJ, or the GSV below the knee, faster laser fiber
withdrawal rates, ~3 mm/second, are employed to minimize the risk of injury to nontarget
tissues. These laser energy parameter guidelines are outlined in Table 25-1.
FIGURE 25-5. Withdrawal of laser fiber and sheath (note marks on sheath) at an average
rate of 2 mm/second as laser energy is delivered from the junction to the vein entry point
using 14 W in continuous mode.
TABLE 25-1 LASER ENERGY PARAMETER GUIDELINES FOR 810-nm
Vein segment Power (W) Withdrawal rate (mm/s) Energy delivered (J/cm)
Proximal third 14 1 140
Middle third 14 2 70
Distal thirda 14 3 47
a Suggested for vein segments close to skin, nerves, or arteries, below knee, etc.
Class II (30- to 40-mm Hg) graduated compression stockings are placed on the patient
immediately following endovenous laser treatment and worn for a minimum of 2 weeks at all
times, except to sleep or shower. The purpose of graduated support stockings is to lower the
risk of superficial thrombophlebitis in tributary varices that will shrink once the underlying
saphenous vein reflux is eliminated. Graduated compression stockings, in addition to immediate
and frequent ambulation following endovenous laser treatment, also increases the velocity of
blood flow in the deep veins, reducing the likelihood of deep vein thrombosis.
Most patients will note significant improvement or resolution of symptoms within a month
following endovenous laser treatment but will require additional procedures to completely
eradicate the visible varicose tributaries and realize the full benefits of treatment. Compression
sclerotherapy and ambulatory phlebectomy are the most commonly used techniques to
accomplish this. The ideal timing of adjunctive procedures has been debated. Those
practitioners who advocate waiting note that most patients will experience a reduction in the
size and fullness of associated varices, making ancillary treatments easier and more effective.
In some cases, improvement is so dramatic and complete following endovenous laser ablation
that additional procedures are not necessary. Proponents of performing adjunctive procedures
at the same sitting as endovenous ablation cite decreased treatment sessions and lower risks
of superficial phlebitis, particularly in large varicose tributaries following elimination of the
underlying truncal reflux. Occasionally, treatment of nonsurface tributary veins or persistence of
clinically significant perforator reflux will require US-guided sclerotherapy with foam or strong
liquid sclerosants.
Post-Endovenous Laser Follow-up

Many patients will develop ecchymosis over the treated site due to puncture of the vein during
access and administration
of tumescent anesthesia. This is of no medical consequence and will resolve within weeks
following endovenous laser. Some patients may experience mild discomfort over the treated
vein beginning hours after the procedure and resolving within 24 to 48 hours. Many patients will
also note a delayed tightness and mild to moderate tenderness over the treated vein,
particularly over the distal segment. This sensation, described as a pulling, will usually start at
the end of the first week following endovenous laser treatment, and resolve by week 2 or 3.
This delayed pain does not correspond to the presence or degree of bruising and is most likely
caused by transverse and longitudinal retraction of the vein as the acute inflammation
transitions to cicatrisation. Most patients feel better with graduated support stockings and
ambulation, and nonsteroidal anti-inflammatory use is required in only a minority of cases.
Outcomes
The technical success of endovenous laser treatment is defined as a procedure with successful
access, crossing of the segment to be treated, adequate emptying of the vein, administration of
tumescent anesthesia, and delivery of laser energy to the entire incompetent segment. Clinical
success is defined as permanent occlusion of the treated vein segments with successful
elimination of related varicose veins and improvement in the clinical classification of patients by
a certain time interval after the procedure.
In addition to clinical examination, DUS is essential for evaluating treatment success following
endovenous laser ablation. Most practitioners perform DUS within 1 week following endovenous
laser, at completion of treatment, and yearly thereafter. Duplex US criteria for successful
treatment are important to recognize. One week following endovenous laser, DUS imaging will
reveal a noncompressible vein, minimally decreased in diameter, with echogenic,
circumferentially thickened vein walls, and no flow seen within the entire treated vein lumen
upon color Doppler interrogation. Adequate treatment should result in occlusion due to vein wall
injury with resultant inflammation. If present, intraluminal thrombus should be minimal and a
secondary phenomenon, not the primary cause of occlusion, which would result in
recanalization. At 3- to 6-month follow-up, DUS should demonstrate continued target vein
occlusion, with a marked reduction in vein diameter. The vein should be absent or only a
minimal residual cord visible upon DUS imaging 1 year and beyond (8,9).
The following are results on the first 1,000 limbs treated with endovenous laser using an 810-
nm diode laser source (Diomed Holdings Inc., Andover, MA) for saphenous vein reflux at our
center. Successful endovenous laser treatment, defined using the DUS criteria above, was seen
in 98% (982/1,000) of treated limbs at up to 60 months of followup. Ninety-nine percent
(457/460) of treated vein segments remained occluded at more than 2 years of follow-up. The
majority (13/18) of treatment failures occurred prior to 1 year and there has been only 1 failure
in >500 veins treated with 14 W. All veins treated with at least 70 J/cm of laser energy have
remained closed (29).
Clinical examination correlated well with DUS findings. All subjects demonstrated improvement
of visible varicosities. A representative lower extremity before treatment and the appearance 1
month following endovenous laser treatment is shown in Fig. 25-6. All subjects presenting with
leg pain due to SVI noted resolution or substantial improvement in associated symptoms by 6
months.
Non-puncture-site bruising was noted in one quarter of limbs at 1-week follow-up. Ecchymosis
resolved in all subjects prior to 1-month follow-up. The majority of subjects felt a delayed
tightness beginning 4 to 7 days postlaser and lasting 3 to 10 days. Superficial phlebitis of an
associated varicose tributary was noted in ~5% of treated limbs following endovenous laser
ablation. Most cases of superficial phlebitis required no treatment, although symptomatic
patients were encouraged to ambulate, continue use of graduated compression, and take over-
the-counter anti-inflammatory medications as needed. There have been no skin burns,
paresthesias, DVTs, or other adverse reactions. The procedure was well tolerated by all
subjects using strictly local anesthesia.
Several investigators have reported similar success rates of endovenous laser ablation of the
GSV (25, 26, 27,30, 31, 32, 33). These studies have consistently shown successful
nonthrombotic occlusion of the target truncal vein in 90% to 100% of cases, with very rare
recanalizations of previously occluded vein segments. Clinical improvement was noted in almost
all cases following successful truncal vein occlusion. Patient acceptance was high and adverse
reactions were extremely rare, with heat-related complications such as DVTs, paresthesias,
and skin burns virtually nonexistent.
Discussion
Performing endovenous ablation of the GSV without division of each of the tributaries at the
SFJ goes against a fundamental rule in saphenous vein surgery; however, the combined
experiences with endovenous ablation procedures have shown lower recurrence rates than with
surgical ligation and stripping. Staying out of the groin and preserving venous drainage in normal
competent tributaries while removing only the abnormal refluxing segments may not incite the
neovascularization often seen following surgical treatment. Studies have shown that recurrence
of varicose veins after GSV stripping occurs early (34), with 73% of limbs destined for
recurrent varicosities at 5 years already having them at 1 year (35,36). Our results have
supported this, with late recanalization of target veins rarely occurring more than 1 year
following endovenous laser ablation. Although true recanalization is uncommon, recurrence of
varicose veins is not. Even successful endovenous ablation does not entirely eliminate a
patient's propensity to develop venous insufficiency. This can occur from untreated portions of
the saphenous vein, incompetent tributaries, perforator reflux, or worsening of veins during
pregnancy. Practitioners must counsel patients that venous insufficiency is a chronic condition.
Over the past 5 years, we have gained a better understanding of the usefulness of tumescent
anesthesia in endovenous ablation. Emptying of the vein with tumescent fluid, Trendelenberg
positioning, external compression, or a combination of these and other means is critical to
ensuring treatment safety and efficacy. Since blood is a chromophore for all laser wavelengths
used for endovenous ablation, too much blood will lead to inadequate vein wall damage.
Occlusion by thrombosis will result in eventual vein recanalization and treatment failure. The
goal is to maximize laser energy transfer to the vein walls by providing maximal contact of the
vein walls and laser fiber tip.
As mentioned earlier, another one of the goals of proper tumescent anesthesia is to separate
nontarget structures from the target vein. Ultrasound is critical in guiding delivery of dilute
lidocaine into the proper location. The tumescent fluid should be delivered between the target
vein and adjacent nontarget tissues. One can imagine that delivery of fluid in the wrong plane
could compress adjacent structures against the vein, exposing them to possible injury during
laser energy delivery rather than separating and protecting them. This is particularly important
when treating veins known to travel in close proximity to nerves and arterial branches such as
the GSV below the knee or the SSV.
FIGURE 25-6. A: Left lower extremity with large varicose veins and venous stasis skin
changes due to SFJ incompetence with GSV reflux. B: Marked improvement in
appearance of the leg 1 month following endovenous laser ablation of the GSV.
The remarkably low rate of true adverse reactions following endovenous laser ablation
compares favorably to the rates with other treatments of saphenous vein reflux such as surgery
and other catheter-based procedures such as radiofrequency. Complications related to
endovenous techniques using radiofrequency have included skin paresthesias, skin burns,
DVTs, and pulmonary emboli. Although liberal use of tumescent anesthesia has helped reduce
the incidence of heat-related injury to adjacent nontarget tissues, persistence of paresthesias
(13% to 15%), clinical phlebitis (2% to 20%), thermal skin injury (4% to 7%), and DVT (1% to
16%) (37, 38, 39, 40) have resulted from radiofrequency ablation.
Although speculation exits regarding differences in success of endovenous laser versus
radiofrequency ablation, there is limited published literature comparing these techniques. One
recent study by Black et al. demonstrated acceptable results with both procedures at 6
months, with 100% (126/126) of veins closed with endovenous laser and 91.5% (118/129)
closed with radiofrequency. Eight of the radiofrequency failures were retreated with
radiofrequency. Interestingly, three veins failing repeat radiofrequency were successfully closed
with endovenous laser treatment (41). Despite these differences, it is important to emphasize
that both of these minimally invasive techniques offer advances in both safety and efficacy
versus traditional surgical treatment of saphenous vein reflux.
The combined experience of multiple practitioners performing endovenous laser ablation over
the past 5 years has led to several lessons learned. It has been postulated by some
investigators that absorption of laser energy by blood plays a role for homogeneous distribution
of thermal damage to the inner vein wall (42); however, it is apparent that steam formation from
blood absorption is, in itself, inadequate to result in sufficient vein wall damage. Most treatment
failures seem to occur within the first year following treatment, with the majority of these
becoming evident by 6 months. Proximal portions of truncal veins appear to be the most difficult
to treat successfully. These vein segments are exposed to the highest central venous pressures
and are the least prone to venospasm. Emptying the vein by Trendelenberg positioning,
tumescent anesthesia, or other means is especially important here and is critical to long-term
procedural success. Transfer of laser energy to the vein walls via direct contact between the
laser fiber tip and the vein is the predominant mechanism of action of endovenous laser
ablation. Maximizing this contact will result in adequate vein wall damage with eventual fibrosis,
whereas too much blood will lead to nonocclusion or occlusion by thrombosis with eventual re-
opening.
Examination of treatment parameters has also led to optimization of endovenous laser
technique. Studies by Timperman et al. (28) and Proebstle et al. (43) have shown that the
success of endovenous laser is dependent on the amount of laser energy, with treatment
failures virtually nonexistent when at least 70 J is delivered per centimeter of treated vein. The
vein re-openings seen within the first months following endovenous laser likely represent
inadequate vein wall heating with thrombus recanalization. This is either because of excessively
rapid pullback of
the laser fiber or insufficient vein emptying resulting in poor transfer of thermal energy to the
vein wall. True recanalizations of treated veins can occur but appear to be uncommon. Initial
vein wall diameter is unrelated to procedural success and there appears to be no size limit of
vein that can be successfully treated with endovenous laser as long as adequate vein emptying
and laser fiber-to-vein wall contact are achieved. Veins with initial diameters >30 mm have been
successfully closed with endovenous laser by several practitioners.
Wavelengths of 810, 940, 980, 1,064, and 1,320 nm have all been used successfully for
endovenous laser treatment. Despite attempts by industry or proponents of specific
wavelengths to distinguish themselves from the pack, the techniques employing the various
wavelengths are virtually identical. All of these wavelengths are absorbed by blood to varying
degrees (44). The primary mechanism responsible for delivery of laser energy to the vein wall
for all of these wavelengths is identical: laser energy is delivered to the vein wall via direct
contact. It is therefore not surprising that all wavelengths used for endovenous laser ablation
have worked well and it is doubtful that one wavelength will excel above all others. Although
perhaps scientifically disappointing, this is good news for patients since it points to the
extremely high degree of success and extraordinarily low complication rate of the current
technique.
CONCLUSIONS
SVI is an extremely prevalent condition, but despite its potentially disabling nature and high
socioeconomic cost, most patients suffering from SVI are poorly evaluated and often
mismanaged. Fortunately, advancements in noninvasive examination, in particular, DUS, have
improved our understanding of SVI by allowing direct visualization and testing of underlying
pathways of reflux. Making a better diagnosis has led to better treatments. In particular, new
and improved minimally invasive techniques for treatment of incompetent veins now provide
practitioners with safe and effective options for managing the whole spectrum of superficial
venous disease.
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> Table of Contents > Section III - Vascular Interventions > Part B: - Systemic Venous Interventions > Chapter 26 - Gonadal
Embolotherapy
Chapter 26
Gonadal Embolotherapy
Eric Reiner
Jeffrey Pollak
Robert I. White Jr.
Varicocele and pelvic congestion syndrome (PCS) have some anatomical similarities, and the
techniques for treating each of these entities are similar as well. The symptoms, approach to
diagnosis, and outcomes are quite dissimilar and throughout this chapter they are considered
separately in each section (1, 2, 3, 4, 5).
EPIDEMIOLOGY AND ETIOLOGY

Varicocele
Varicocele is a common condition, affecting 10% to 15% of the male population (1, 2, 3, 4).
Varicocele is the most common cause of male infertility and, when large, may cause pain and
testicular atrophy in adolescents as well as adults. Varicocele is a varicosity of the pampiniform
plexus due to incompetence of the valves of the internal spermatic vein (ISV). There is no
unifying theory to explain incompetence of the ISV, although compression of the left renal vein
between the aorta and the superior mesenteric artery has been advanced as one theory, along
with congenital absence of the valves (1).
Pelvic Congestion Syndrome

Even less is known about the epidemiology and etiology of PCS compared to varicocele. PCS
is present when there is reflux of venous blood down the internal ovarian vein (IOV) either
unilaterally or bilaterally leading to large pelvic varicosities of the parauterine and uterine veins.
Presumably, the valves in the IOV have become incompetent, allowing venous reflux.
Entrapment of the IOV between the aorta and the superior mesenteric artery has been
suggested as a mechanism to explain incompetence of the left IOV but this is just an
anatomical observation in some patients, and not proven (5,6). PCS is more common in
multiparous women and in women with lower extremity varicosities (7).
CLINICAL AND LABORATORY FINDINGS

Varicocele
In children and adolescents with large varicoceles, the patient or the pediatrician notices the
large dilated veins in the upright position. Pain, associated with large varicoceles, is described
as dull and throbbing and is more common during exercise. Smaller varicoceles, not noticed by
patient or doctor, are discovered during evaluation of infertile couples (defined as unprotected
intercourse for 1 year). During the workup of the infertile couple, varicocele is discovered in
30% to 40% of men. At least two semen analyses will usually demonstrate what is referred to
as a stress pattern. Normally there should be near-normal counts of 20 million spermatozoa
per milliliter of semen but the motility will be considerably below the normal value of 60% motile
forms. This stress pattern will improve after correction of the varicocele in about 50% to 60%
of men. Pregnancy results in about one third of couples after varicocele repair (1, 2, 3, 4).

There are no specific laboratory findings for patients with PCS but their clinical symptoms are
often dramatic and disabling. Pain associated with PCS becomes progressively worse during
the day and is often described as throbbing and low within the pelvis. It is usually relieved by
assuming the supine position and is often a cause of dyspareunia. Associated findings may be
vulvar varicosities as well as varicosities of the lower extremity (7). Dysmenorrhea may be
present and it is not clear that it is related to PCS (5,8).
ROLE OF IMAGING PRIOR TO THERAPY

Varicocele
Scrotal ultrasound is a simple and noninvasive way to estimate testicular volume, exclude other
pathology, and confirm the presence of varicocele. If the diameter of two or more veins within
the pampiniform plexus is at least 3 mm when supine or if they dilate with valsalva, a varicocele
is present. Doppler ultrasonography may also demonstrate reflux down the ISV (9,10).

It is not uncommon to detect dilated ovarian and uterine veins during multidetector computed
tomographic studies or magnetic resonance venography of asymptomatic women (6,11). In one
recent study of 110 multiparous women and 41 nulliparous women, reflux down the left IOV
was found in 48 of 100 (44%) multiparous women and 2 of 41 (5%) nulliparous women (6).
Retrograde flow was demonstrated through the parauterine and uterine veins into the right IOV
in 24 of 25 women who were multiparous (6). Similar results have been demonstrated in earlier
studies using magnetic resonance imaging to detect enlarged ovarian veins and uterine venous
engorgement (11).
TABLE 26-1 INDICATION FOR SCROTAL IMAGING AND VARICOCELE

EMBOLOTHERAPY
Painful varicocele with exercise
Large varicocele in adolescent with or without testicular atrophy
Persistent varicocele after surgical repair
Varicocele associated with infertility and decreased sperm motility
This is why a careful clinical history is important before considering therapy since so many
multiparous women will have acquired ovarian vein reflux, associated with multiple pregnancies
but without symptoms. Interestingly, the same phenomenon occurs in patients with varicocele,
who may be asymptomatic and without infertility (2). It is not known why some women with
PCS and men with varicocele are symptomatic. This phenomenon has made physicians
skeptical of treating patients with symptomatic PCS as well as men with symptomatic
varicocele.
INDICATIONS AND PATIENT SELECTION

Varicocele
In addition to pain, large varicoceles in adolescents are associated with testicular atrophy.
More consideration should be directed to correcting the male infertility component due to
varicocele in adult patients. Too often, couples with infertility are encouraged or decide on their
own to participate in vitro fertilization rather than correct all the factors that may be operating to
contribute to this problem (2). Indications for varicocele repair are listed in Table 26-1.

Positional symptoms (worse pain with prolonged standing and at end of day) with relief at night
are fairly specific for PCS. Because uterine fibroids, adenomyosis, and other ovarian and
uterine pathology may be present, we obtain a pelvic magnetic resonance study with and
without contrast material. This study may identify another cause(s) of pelvic pain and may
confirm the presence of large ovarian and uterine veins. Dyspareunia may be present in up to
30% of women (5,8).
PROCEDURAL AND TECHNIQUE CONSIDERATIONS

General
For both varicocele and PCS patients, all occlusions are performed percutaneously from the
right femoral vein as has been our standard since beginning gonadal embolotherapy in 1978
(12). All studies are done on an outpatient basis and we have not had to readmit patients for
control of pain associated with the occlusion.
All patients are hydrated with intravenous fluids during the study and for the 4 hours after
removal of catheters. We have used conscious sedation except in adolescents <14 years old,
who are more comfortable with outpatient general anesthesia. While there are many reports of
treating varicocele and PCS from a percutaneous jugular vein approach, we are just as
comfortable and believe our technical success is no lower than in those series performed from
the internal jugular vein (13,14).
Minimal pain occurs during the occlusions and is easily managed by standard moderate
sedation. During the first 48 hours after the procedure, using our new technique, with 3%
sodium tetradecyl foam and pushable fibered coils, patients with varicocele may experience
slight scrotal and or back discomfort, which is easily managed with acetaminophen or overthe-
counter ibuprofen (15). Patients with PCS requiring either bilateral or unilateral occlusion of the
ovarian veins and parauterine and uterine plexus of veins receive a prescription for 48 hours of
Ketoralac (Toradol) and we have not needed oral narcotics for either PCS or varicocele
patients. Patients are encouraged to resume normal activities within 48 hours after the
procedure.
Access and Catheters

The right femoral vein is entered percutaneously and a 7-Fr standard indwelling sheath is
placed.
Left Internal Spermatic/Ovarian Vein Approach

The anatomy of a left-sided varicocele and pelvic congestion syndrome is shown in Fig. 26-1. A
7-Fr Hopkins curve guiding catheter for gonadal venography (Cordis, Miami, FL) is passed up
the femoral vein and inferior vena cava over a floppy Bentson guide wire and positioned above
the left renal vein (16). The guide wire is removed and the catheter gently withdrawn until it
advances into the left renal vein. At this point in the procedure in about 50% of patients it will
automatically enter an incompetent ISV or IOV as the Hopkins shape reforms. If this does not
happen automatically, a hand injection of contrast material is made while the patient performs a
valsalva maneuver. Usually an incompetent left ISV or IOV is identified, and with minimal
manipulation, the 7-Fr guide catheter will be seated within the gonadal vein. In about 15% of
cases, there may be competence of the valves within the proximal ISV/IOV and filling of the
varicocele or uterine venous plexus may arise from hilar or capsular collaterals which enter the
ISV/IOV more inferiorly (17). These alternative pathways can usually be demonstrated during a
renal venogram, performed through the guiding catheter. Alternative access can be achieved by
using a tapered 0.018-in. guide wire and gently probing the competent ISV/IOV or by coaxially
catheterizing the hilar collateral using standard microcatheters. On occasion the normal
ISV/IOV may arise more distal in the left renal vein in the presence of a circumaortic renal vein.
Coaxial catheterization of the distal ISV/IOV is performed with a 5-Fr Glide catheter in either
hockey stick or multipurpose configuration (Terumo, Somerset, NJ). The catheter is moved
lower in the ISV, to the level of the inguinal canal, by advancing it slowly with tiny test injections
of contrast material. The same is done for distal catheterization of the IOV to the level of the
parauterine veins. It is our preference to avoid guide wires when advancing the 5-Fr coaxial
catheter if possible, since guide wires may induce spasm that can impair the ability to perform
distal occlusion.
Right Internal Spermatic Vein/Ovarian Vein Approach

A 5-Fr Simmons 1 or 2 shape catheter (Cordis or Cook, Inc., Bloomington, IN) is re-formed
over the caval bifurcation or in the renal veins. When reshaped it is advanced up the inferior
vena cava, beyond the right renal vein. Using hand injections of contrast material the catheter is
withdrawn into the right renal vein and then retracted and advanced with gentle test injections
from the right lateral to the anterior surface of the inferior vena cava just below the right renal
vein until the orifice of the right ISV/IOV is identified. Once identified, the right ISV/IOV is
entered gently with the tip of the Simmons 1 or 2 catheter and seated. We then place a 3-Fr
microcatheter with two platinum markers and an 0.021 in lumen (Renegade, Boston Scientific,
Natick, MA) deep into the right ISV/IOV to the levels for occlusion, which are the same as for
occlusion of the left ISV and IOV (Figs. 26-2A to C).
FIGURE 26-1. Diagrams of (A) left internal spermatic vein (ISV) and varicocele and (B)
right and left internal ovarian vein (IOV) with retrograde filling of large parauterine and
uterine venous plexus. Note all the potential pathways that may become operational after
surgery or embolotherapy for each condition. These potential pathways are common
causes of persistence or recurrence after therapy.
OCCLUSION TECHNIQUES AND DEVICES
Varicocele
Figure 26-3 demonstrates our left varicocele occlusion techniques and devices from 1992 to
2004 (Fig. 26-3A) and since mid 2004 (Fig. 26-3B). Prior to 2004, we used a four-position coil
occlusion technique beginning low in the ISV at the level of the internal inguinal canal, just above
the superior ramus of the pubis, and then bridging the upper one third of the sacroiliac joint and
immediately above the sacroiliac joint and then at the upper level of the ISV about 2 to 3 cm
below the level of where the left ISV entered the renal vein (15). These coil positions were
based on our experience published during the 1980s that demonstrated the common sites of
parallel collateral and hilar collateral entry into the ISV (2,15). Beginning in June 2004, when
sodium tetradecyl sulfate (STS) was approved for varicose veins, we began to use it in a foam
preparation with equal amounts of air (15): 3% STS foam is injected during compression of the
ISV at the level of the pubis symphysis where the pampiniform plexus joins the ISV (15). This is
done during injection of 1 to 3 mL of 3% STS foam to prevent phlebitis of the pampiniform
plexus.
The first coils are placed before the foam injections to increase resistance within the ISV; this
helps to identify parallel collaterals, which are subsequently filled with foam to promote
thrombosis. Usually one or two injections of 1 to 3 mL of 3% STS foam are injected to displace
the contrast material, filling the ISV and parallel collaterals.
An important deviation from our standard technic prior to 2004 is the omission of the final and
fourth nest of coils just below the left renal vein. This theoretically will allow the
recatheterization of the proximal left ISV in the event of persistence (recurrence) of the
varicocele (15). Figure 26-4 demonstrates hilar and parallel collaterals of the ISV, which may
lead to persistence after treatment. These variations may not be immediately apparent and
persistence of varicocele after embolotherapy is thought to arise through these channels. We
believe our modified technique, which combines foam and coils, will be even more effective than
coils alone, which were the U.S. standard prior to 2004 and the availability of STS foam (15).
For occlusions of the right ISV, the techniques including foam and pushable fibered coils are the
same as for the left except we are using 0.018-in. micronester coils (Cook, Inc.) in the same
locations as for left-sided varicocele. Placement of coils into a tight occlusion mass is facilitated
by the double marker microcatheter (Renegade 0.021; Boston Scientific). The distal marker is
left within the first tightly compacted coil mass and usually a second coil is placed until we have
a firm cross-sectional occlusion of the ISV at each level (Figs. 26-2A to C).
FIGURE 26-2. Occlusion technique for right ovarian vein in a young woman with debilitating
pelvic pain, desirous of more children. A: The Simmons 1 catheter is shown, and through it
a double marker microcatheter is coaxially placed. B: A hand injection of contrast material
in the distal right IOV demonstrates varices and, on later views with Valsalva, filling of the
parauterine plexus. Two depositions of 2 to 3 mL of 3% STS foam were delivered to
displace the static contrast material. C: The final position of coils and site of foam delivery
are seen in the right IOV. Note the placement of coils and foam on the left side. In both
ovarian veins the upper portion of the vein is left patent. Note also the intrauterine device to
prevent pregnancy. This patient's pain was so severe during her last pregnancy that the
IUD was placed until she had diagnosis and treatment for PCS.
FIGURE 26-3. Schematic of (A) varicocele occlusion technique used between 1992 and
2004 and (B) new technique in combination with STS foam. In A and B, the first nest of
coils is placed in the ISV at the level of the internal inguinal ring. Hilar and parallel collateral
pathways are drawn, showing the common mechanisms for persistence of a varicocele
following embolotherapy or surgery. B: After placing the first nest of coils 2 to 3 mL of STS
foam is injected above the site of occlusion. If additional parallel collaterals are identified, a
second injection is done at the level of the second nest of coils. A third nest is placed in the
ISV above the sacroiliac joint. We leave the rest of the ISV unoccluded as long as no other
parallel collaterals are identified. By leaving the upper ISV patent, we have the opportunity
to re-treat the patient should persistence occur.

Left Ovarian and Uterine Vein Technique
The occlusion technique we currently use with 3% STS foam and a two- or three-position coil
occlusion is shown diagrammatically in Fig. 26-5. Unlike varicocele, the injection of foam at the
distal position in the left IOV is designed to penetrate the parauterine and uterine plexus and
displace static contrast material. In general, it is our intent to occlude as much of the
parauterine and uterine venous plexus with the foam, while in varicocele we hope to prevent
occlusion of the pampiniform plexus but promote occlusion of all ISV collaterals and the main
ISV. At least two foam injections are given at the lower position in the left IOV, followed by
additional foam higher at the level of the second coil position. As with varicocele, a final and
fourth coil nest is not placed immediately below the entrance of the IOV into the left renal vein.
Since recurrences of symptoms in patients with PCS are much more common than in
varicocele, we believe that leaving the proximal IOV open will allow more ready access to
parallel collaterals not occluded in our initial procedure (Fig. 26-6).
Right Ovarian Vein Technique

Since there is usually free flow between the left and the right parauterine and uterine veins in
the upright position, it is important to attempt occlusion of the right IOV as well as the left IOV.
This is performed as shown in Fig. 26-2. Hiromura et al. have described three degrees of
ovarian reflux, with Grade 1
involving just the left IOV and Grade 3 demonstrating cross-filling through the parauterine and
uterine veins into the right IOV (6). In Figs. 26-7 A to C, we demonstrate the anatomy that we
feel is most commonly present in PCS and would be considered Hiromura Grade 3 (6). Since
most imaging and gonadal venography is performed supine, one would not expect always to
see the connections between the left and the right IOV, through the parauterine and uterine
plexus.
FIGURE 26-4. Persistence of varicocele after standard technique from 1992 to 2004. The
drawing demonstrates the many ways that varicoceles can rerperfuse after coil
embolization alone. In this theoretical example, persistence could be due to parallel
collaterals bypassing the coils. In this example the bypassing collateral shown medially
was not able to reconstitute the varicocele because of the distal coils. Laterally, though,
despite occlusion on either side of the colic collateral, hilar and capsular veins reconstituted
parallel collaterals which enlarged and led to persistence. Using coils alone, our
persistence rate was 10% in adults and close to 20% in adolescents with large
varicoceles. With the availability of STS foam, our initial experience in 16 adolescent
patients led to only 1 persistence. STS foam theoretically should lead to a much lower
persistence rate, and we believe that, when used in combination with coils, most of the
potential ways in which varicocele may recur will be occluded (15).
With these considerations in mind, we have adopted the same technique we use for right
varicocele and applied it to catheterization of the right IOV. Using the Simmons 1 or 2 shape, 5-
Fr Cordis catheter, the right IOV is gently probed. Often there is a partially competent valve
present, and with a mild valsalva, reflux down the right IOV will be demonstrated. Rather than
attempt to seat the 5-Fr Simmons 1 or 2 catheter through the partially incompetent right IOV,
we place a microcathteter through the 5-Fr Simmons catheter that is now acting as a guiding
catheter. From this point on, the occlusion technique is just the same for the right IOV as for
the left side (Fig. 26-2). With the microcatheter deep within the right IOV, hopefully in the right
parauterine vein plexus, we displace static contrast material with at least two injections of 2 to
4 mL of 3% STS foam.
FIGURE 26-5. Diagram of our technique for treating patients with pelvic congestion
syndrome with 3% STS foam and pushable fibered coils since mid-2004. The goal of
therapy is to displace contrast material in the parauterine and uterine plexus with 3% STS
foam and to occlude in the standard two or three lower locations with pushable fibered
coils. By leaving the upper portion of both the right and the left IOV open, recurrence of
PCS should be approachable.
Patients will often experience some pain during this injection, and it is usually just transient.
During the procedure we give 30 mg of IV Ketoralac before each IOV occlusion. Micronester
coils, 0.018 in. (Cook, Inc.), are placed in a tightly compacted mass in the distal right IOV as on
the left side and then in a second position where the right IOV crosses the upper one third of
the sacroiliac joint. Before placing these coils, we usually apply one or two additional foam
injections with the patient holding a valsalva, to penetrate deeply any of the parallel collaterals
with the foam.
As on the left side, the upper portion of the right IOV is not occluded with coils, to leave access
should a recurrence of symptoms occur.
RESULTS
Varicocele
In a meta-analysis of 65 studies by Schlesinger and associates, published in 1994, following
surgical varicocelectomy, the
average pregnancy rate in infertile couples was 37%. Similar findings have been reported after
transcatheter management of varicocele by embolotherapy (2, 3, 4,14,18).
FIGURE 26-6. Persistence of PCS prior to STS foam using coils alone. A: The Hopkins
curved guiding catheter is seen in the left renal vein. This patient was pain-free after both
ovarian veins were occluded 2 years earlier using coils alone. Note that the upper level of
coils was placed just below the entrance of the left IOV into the left renal vein. B: A limited
left renal venogram documents that the recurrence, 2 years later, was due to a hilar
collateral that bypassed the coils. STS foam was not available, and despite occlusion of
the hilar collateral, after catheterization with a microcatheter and microcoils, the patient's
symptoms persisted. Leaving the upper right and left IOV patent since mid-2004 should
make it easier to re-treat our recurrences, and in this example we would use foam placed
via a microcatheter deep within the hilar collateral.
In two articles from the 1990s pregnancy rates in infertile couples, following surgical
varicolectomy versus embolization, were shown to be equivalent and in both series 30% to 35%
of infertile couples achieved pregnancy (19,20). Varicocele embolization is associated with
fewer complications and quicker recovery times than surgical repair. Recurrence rates vary but
conservatively about 10% of patients will have recurrence. European results are similar, but
with widespread use of sclerosants in combination with coils, most series have less than 10%
recurrence rate. We are hopeful that our adoption of STS foam will also be associated with
less recurrence (15).

Far fewer data are available documenting long-term outcome after transcatheter
embolotherapy of patients with PCS than for varicocele occlusion. The recent results by
Venbrux et al. in 2002 and a follow-up study by Kim et al. in 2006 demonstrated long-term relief
of PCS after transcatheter embolotherapy (5,8). In Kim and coworkers' study 108 of 127
(85%) patients had good short-term results (5). Ninety-seven patients completed long-term
clinical follow-up with a mean time of 43 months. Overall in this group, followed for almost 4
years, 83% had significant relief of pain (5).
In the Venbrux et al. and Kim et al. approach, they occluded one or both ovarian veins in a first-
stage procedure (5,8). A second procedure was performed 4 to 6 weeks later. Temporary
balloon occlusion of each iliac vein was performed sequentially. Liquid sclerosant in combination
with gelfoam was injected retrograde into the parauterine and uterine plexus in almost all their
patients (5,8). Prior outcomes of treatment for PCS, demonstrating short-term relief of
symptoms, are summarized in the recent article by Kim et al. (5).
At this time it appears that more work needs to be done to prove long-term efficacy of bilateral
ovarian and uterine plexus obliteration with STS foam and coils. STS foam, 3%, in combination
with pushable fibered coils has been successful in treatment of large adolescent varicocele
(15). Based on our experience with coils alone since 1992 and coils and 3% STS foam since
2004, we believe that bilateral IOV occlusion will be equally successful in women with PCS.
In the presence of large pelvic varicosities total hysterectomy relieves only 60% to 70% of
symptoms so it appears that, if more comparative approaches using transcatheter
embolotherapy are shown to be as effective as hysterectomy, as with varicocele, transcatheter
embolotherapy will become the procedure of choice (21).
FIGURE 26-7. A: Excellent demonstration with serial imaging of filling of the distal left IOV
and parauterine venous plexus. B, C: The right IOV, internal iliac and common iliac veins,
and inferior vena cava fill later. Undoubtedly, in the upright position, when these patients
are so symptomatic, there is no retrograde filling of the uterine plexus via the internal iliac
veins. We believe, based on our preliminary experience, that filling of other parauterine
plexi can be accomplished readily with STS foam, obviating the need for retrograde
internal iliac vein occlusion as has been advocated by others (5,8).
POSTPROCEDURAL MANAGEMENT
Varicocele
In adolescents with pain and testicular atrophy and adults with infertility, 3- to 4-month
evaluation is all that is required. Recurrence of varicocele is in reality a misnomer; instead the
varicocele persists due to unoccluded collaterals. In adolescents, we perform a testicular
ultrasound at 1 to 3 months, and if the varicocele is gone, that concludes follow-up. In infertile
men, we are less likely to repeat or perform testicular ultrasound but instead examine a semen
analysis (usually at least two) 3 months after repair, and the motility should have improved with
successful treatment.
We encourage patients to return to school or work the day following the procedure, and in the
few who experience mild back or scrotal pain, we treat symptomatically with acetaminophen or
low doses of ibuprofen.

Patients recovering from outpatient treatment may notice almost-immediate relief of their
symptoms and others may take a few weeks to improve. Some patients may have worse pain
for several days following the procedure, presumably due to thrombosis of uterine and ovarian
veins. We encourage them to return to their normal activities, the day after embolization. We
have not routinely performed any postocclusion imaging, but if recurrent symptoms develop,
they are restudied.
References
1. Zini A. Varicocele: evaluation and treatment. J Sex Reprod Med. 2002;2(3): 119-124.
2. White RI Jr. Varicocele management by transcatheter embolotherapy. In: Pollack HM,

McClennan BL, eds. Clinical Urography. 2nd ed. Philadelphia: W. B. Saunders; 2000:3375-
3379.
3. Shlansky-Goldberg RD, VanArsdalen KN, Rutter CM, et al. Percutaneous varicocele

embolization versus surgical ligation for the treatment of infertility: changes in seminal
parameters and pregnancy outcomes. J Vasc Interv Radiol. 1997;8:759-767.
4. Belman AB. The adolescent varicocele. Pediatrics. 2004;114:1669-1670.
5. Kim HS, Malhotra MD, Rowe PC, et al. Embolotherapy for pelvic congestion syndrome:
long term results. J Vasc Interv Radiol. 2006;17:289-297.
6. Hiromura T, Nishioka T, Nishioka S, et al. Reflux in the left ovarian vein: analysis of MDCT
findings in asymptomatic women. AJR. 2004;183:1411-1415.
7. Black CM, Collins J, Hatch D, et al. Pelvic venous congestion syndrome and lower
extremity superficial venous reflux disease. Presented at SIR, New Orleans, LA; 2005:
abstract 123.
8. Venbrux AC, Chang AH, Kim HS, et al. Pelvic congestion syndrome (pelvic venous
incompetence): impact of ovarian and internal iliac vein embolotherapy on menstrual cycle
and chronic pelvic pain. J Vasc Interv Radiol. 2002;13:171-178.
9. Kass EJ, Freitas JE, Bour JB. Adolescent varicocele: objective indications for treatment.
J Urol. 1989;142:579-582.
10. Kass EJ, Stork BR, Steinhart BW. Varicocele in adolescence induces left and right
testicular volume loss. BJV Int. 2001;87:499-501.
11. Nascimento AB, Mitchell DG, Holland G. Ovarian veins: magnetic resonance imaging
findings in an asymptomatic population. J Magn Reson Imaging. 2002;15:551-556.
12. Walsh PC, White RI Jr. Balloon occlusion of the internal spermatic vein for the treatment
of varicoceles. JAMA. 1981;246:1701-1702.
13. Halden W, White RI Jr. Outpatient embolotherapy of varicocele. Urol Clin North Am.
1987;14:137-144.
14. Zuckerman AM, Mitchell SE, Venbrux AC, et al. Percutaneous varicocele occlusion:
long-term follow-up. J Vasc Interv Radiol. 1994;5:315-319.
15. Reiner E, Pollak JS, Henderson KJ, et al. Initial experience with 3% sodium tetradecyl
sulfate foam and fibered coils for management of adolescent varicocele. In press, SVIR.
16. Trerotola SO, Venbrux A, Savader SJ, et al. Guiding catheter for varicocele
17. Marsman JW. The aberrantly fed varicocele: frequency, venographic appearance, and
results of transcatheter embolotherapy. Am J Roentgenol. 1995;164:649-657.
18. Schlesinger MH, Wilets IF, Nagler HM. Treatment outcome after varicocelectomy: A
critical analysis. Urol Clin North Am. 1994;21:517-529.
19. Sayfan J, Soffer Y, Orda R. Varicocele treatment: prospective randomized trial of 3

methods. J Urol. 1992;148:1477-1479.
20. Dewire DM, Thomas AJ Jr, Falk RM, et al. Clinical outcome and cost comparison of
percutaneous embolization and surgical ligation of varicocele. J Andol. 1994;15 (Suppl):38-
42.
21. Beard RW, Kennedy RG, Gangar KF, et al. Bilateral oophorectomy and hysterectomy in
the treatment of intractable pelvic pain associated with pelvic congestion. Br J Obstet
Gynaecol. 1991;98:998-992.
> Table of Contents > Section III - Vascular Interventions > Part C: - Liver and Portal Venous Interventions > Chapter 27 -
Endovascular Treatment of Budd-Chiari Syndrome
Chapter 27
Endovascular Treatment of Budd-Chiari Syndrome
S. Furui
Obstruction of hepatic venous outflow with the consequent characteristic clinical features such
as abdominal pain, hepatic dysfunction, hepatosplenomegaly, ascites, and esophageal varices
constitutes Budd-Chiari syndrome (BCS). The site of the obstruction can be either the hepatic
veins (HVs; Type I) or the intrahepatic inferior vena cava (IH-IVC; Type II). This site of
obstruction appears to have a geographic predilection: Type I BCS is generally reported in
Europe and the United States (1, 2, 3, 4, 5, 6), whereas Type II is more common in East Asia
and South Africa (7, 8, 9). However, both types have almost-equal frequency in India and Saudi
Arabia (10,11).
BCS may be treated with medical, endovascular, or surgical methods. There have been many
reports of the results with each approach. However, these results are difficult to place in
context, as the studies contain a limited numbers of patients, and there have been no controlled
prospective or randomized studies (1, 2, 3). This chapter describes treatment of BCS caused
by HV obstruction or IVC obstruction with endovascular procedures. These procedures include
balloon angioplasty, stenting, and transjugular intrahepatic portosystemic shunting (TIPS).
BUDD-CHIARI SYNDROME CAUSED BY HEPATIC VEIN

OBSTRUCTION (TYPE I)
Type I BCS occurs predominantly in adult females (mean age, ~ 35 years) (5,6). Seventy-five
percent of patients are known to have an underlying hypercoagulable condition (1, 2, 3). These
include myeloproliferative disorders (e.g., polycythemia rubra vera, essential thrombocythemia,
and myelofibrosis), paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, inherited
deficiencies of protein C, protein S, or antithrombin III, factor V Leiden mutation, and
prothrombin mutation. Thrombosis of the HVs associated with BCS is a relatively frequent
complication of Behcet's disease (2,12). Use of oral contraceptives, pregnancy, and
postpartum state are risk factors (1,2). Doppler ultrasound, magnetic resonance imaging
(MRI), computed tomography (CT), hepatic venography, and percutaneous or transjugular liver
biopsy are used to establish the diagnosis (1, 2, 3, 4).
There are two subtypes of HV obstruction that can cause BCS (1,13, 14, 15): diffuse
thrombosis of the HV (Fig. 27-1) and short-length obstruction at the ostium or terminal part of
the main HV (Fig. 27-2). The latter is considered as a sequel of previous HV thrombosis and
was noted on imaging examinations in 25% of Type I BCS in one French study (13).
Common signs of BCS caused by HV obstruction are hepatosplenomegaly, ascites, jaundice,
and leg edema (1, 2, 3, 4). These findings are thought to result from the following interrelated
events (2,4): acute HV phlebitis (causing pain and fever) leads to increased hepatic sinusoidal
pressure and congestion and to portal hypertension. The congestion causes ischemic
hepatocyte necrosis, leading to fibrosis, and nodular regenerative hyperplasia. If the necrosis is
massive, hepatic failure develops. The above sequence of events suggests that most
symptoms of BCS can potentially improve, if the hepatic sinusoidal pressure is reduced by
recanalization of the occluded HVs, creation of a portosystemic shunt, or spontaneous
development of portosystemic collaterals.
In addition, patients with Type I BCS often show combined obstruction of the IH-IVC due to
compression by the hypertrophied caudate lobe, or thrombosis (4,6), leading at times to dilated
superficial veins. Up to 25% of patients with Type I BCS have associated extrahepatic portal
vein thrombosis due to either an underlying hypercoagulable condition or stagnant portal venous
blood flow (6,16). Hepatocellular carcinoma (HCC) is extremely rare in patients with Type I
BCS (17), in contrast to BCS caused by IH-IVC obstruction (Type II), where HCC is reported
more frequently (7,9,18).
Clinically Type I BCS may present with no symptoms at all or there may be a rapid downhill
course, depending on the extent and rapidity of the obstruction and development of portal
venous collaterals. The presentation has been classified into fulminant, acute, subacute, and
chronic based on the disease severity and duration (2,3). The acute form is characterized by a
short illness, abdominal pain, fever, hepatomegaly, ascites, and jaundice, while the chronic form
is characterized by indolent refractory ascites, esophageal varices, and near-normal liver
function tests. The chronic form is more frequent than the acute type (1,2,6). However, several
authors have cautioned that such classifications should be used only for a descriptive
stratification because of the following reasons: (a) the definitions of classifications differ among
the previous reports, (b) the prognostic significance of the classifications has not been
validated, and (c) macroscopic and microscopic changes in the liver often do not reflect the
duration of the disease (e.g., several patients with acute presentation have shown extensive
liver fibrosis, which suggests a long preclinical course) (1,3).
The therapeutic approaches to BCS caused by diffuse HV thrombosis, advocated in recent
papers, are as follows (2, 3, 4,19): (a) asymptomatic patients receive anticoagulation therapy
to prevent further extension of thrombosis and treatment for detectable underlying
hypercoagulable conditions; (b) in symptomatic patients, diuretics or paracentesis for ascites is
added to the anticoagulation therapy, and pharmacological or endoscopic treatment for
esophageal varices is performed when a history of variceal bleeding is present; (c) for patients
in whom there is little improvement of symptoms or who become worse following the above
treatment, TIPS or surgical portosystemic shunting is considered; and (d) liver transplantation is
considered for patients with progressive liver failure.
The treatment of choice for Type I BCS caused by short-length HV obstruction is percutaneous
balloon angioplasty with or without subsequent stenting (3,15). TIPS or surgical portosystemic
shunting is considered only if angioplasty/stenting is unsuccessful.
FIGURE 27-1. TIPS for diffuse HV thrombosis in a patient with antiphospholipid syndrome.
A: Contrast-enhanced CT shows heterogeneous enhancement of the liver, mild
hypertrophy of the caudate lobe, and ascites. B: Inferior vena cavogram shows the IVC to
be patent. C: Transjugular portogram during TIPS procedure. A direct puncture of the
cephalad part of the hepatic IVC was done, a guide wire was advanced to the superior
mesenteric vein, and a catheter was introduced over the guide wire. Contrast injection
shows hepatofugal blood flow through the splenic and inferior mesenteric veins. D:
Transjugular portogram after TIPS placement shows good blood flow through the shunt
into the suprahepatic IVC and right atrium. E: Contrast-enhanced CT obtained 4 weeks
after treatment shows patency of the shunt and disappearance of ascites. The liver now
shows homogeneous contrast enhancement, probably due to improvement of hepatic
congestion.
FIGURE 27-2. Angioplasty for short-length HV obstruction. A: Contrast-enhanced CT
(multiplanar reformation, coronal image) shows ascites, esophageal varices, and a short-
length obstruction (arrow) at the terminal part of the right HV. B: Angiogram before balloon
angioplasty. A 5-Fr sheath was placed in the proximal lumen of the obstruction from a
transhepatic approach, and an angiographic catheter was introduced via the sheath.
Contrast injection via the catheter shows collateral blood flow from the right hepatic lobe
into the IVC via the inferior right HV, and a severe stenosis (arrow) is seen at the ostium of
the HV. C: Radiograph during balloon dilation. A guide wire was introduced through the
catheter and advanced to the hepatic IVC, a 10-Fr sheath was placed from a jugular
venous approach, a loop-snare device was introduced through the 10-Fr sheath, the guide
wire was loop-snared and pulled out from the jugular vein, a balloon catheter (inflated
diameter, 10 mm) was advanced to the stenosis over the guide wire via the jugular vein,
and the lesion was dilated by inflating the balloon. D: Angiogram after treatment shows
good blood flow through the well-dilated inferior right HV. The patient showed
disappearance of ascites 3 week later.
The natural course of Type I BCS is not well known, as most patients these days have received
some form of treatment (1,2). According to a report by Zeitoun et al. (5), the combined survival
in 120 patients who received surgical portosystemic shunting (n = 82) or only medical therapy
(n = 38) was 77%, 65%, and 57% at 1, 5, and 10 years, respectively; the mortality was higher
within 2 years of diagnosis. Survival of treated patients has increased over time, with a 5-year
survival of 50% reported before 1985, compared with 75% reported since then. Four factors
age, response to diuretics for ascites, Pugh score, and serum creatinineare independent
determinants of survival. Murad et al. (6) investigated 237 patients with BCS, of
whom 220 had HV obstruction, who received various kinds of treatment. Overall survival in the
237 patients was 82%, 69%, and 62% at 1, 5, and 10 years, respectively. In the latter study,
four factors were independent determinants of survival: presence of encephalopathy, ascites,
prothrombin time, and serum bilirubin level. Reported survival among patients treated with
surgery differs based on the procedure: it ranges from 57% to 94% at 5 years for surgical
portosystemic shunts (1,4,20, 21, 22) and 50 to 95% at 5 years for liver transplantation (1,22,
23, 24, 25).
Interventional Procedures for Hepatic Vein Obstruction (Type I

BCS)
Angioplasty and Stenting for Short-Length Hepatic Vein
Obstruction
Percutaneous balloon angioplasty, with primary or secondary stenting, has been used for
treatment of BCS caused by short-length HV obstruction (14,15) (Fig. 27-2). Regional
thrombolytic therapy may be required as an adjunctive procedure in selected cases.
Balloon angioplasty for short-length HV obstruction is performed as follows (14). Following
Doppler ultrasound localization of a terminal HV obstruction and a patent proximal lumen, a
sheath is placed in the jugular vein and the tip of an angled catheter is placed at the stump of
the occluded HV. A guide wire is advanced via the catheter through the obstruction and into the
proximal lumen. The catheter is exchanged for a balloon catheter, and the lesion is dilated.
If the occluded HV cannot be treated by the above simpler approach, a combined
transhepatic/transjugular approach may be employed (14): the proximal lumen of the occluded
HV is punctured transhepatically under ultrasound guidance, and a 5-Fr sheath is inserted into
the lumen; a guide wire is introduced and manipulated through the obstruction and into the
suprahepatic IVC or, failing this, a direct puncture of the obstruction is made. A second sheath,
placed through the jugular vein, is used to introduce a loop-snare device and the guide wire is
snared and pulled out from the jugular vein. Then a balloon catheter is advanced over the
guidewire via the jugular vein and the obstruction is dilated (Fig. 27-2). In this method, the
balloon is introduced through the transjugular approach to avoid transgressing the hepatic
parenchyma with a large-diameter sheath.
Regional thrombolytic therapy may be needed if significant thrombus is seen before or after
angioplasty. If there is acute local narrowing due to elastic recoil, a self- expanding metallic
stent is placed to maintain patency. After balloon angioplasty and/or stenting, patients are
placed on intravenous heparin until adequate long-term anticoagulation with warfarin is
achieved, in a few days (14,15).
Several reports, most with a small number of patients, have described the results with
angioplasty for short-length HV obstruction (14,15,26, 27, 28, 29, 30). According to these
limited data, the success rate of the procedure seems to be high and the symptoms are
generally relieved after successful treatment, but reocclusion often occurs after treatment. In a
report from the United Kingdom (14), balloon angioplasty ( stenting) was attempted in 21
cases, with an initial success rate of 86%. Reocclusion was found in 6 (38%) of the 16 surviving
cases (range of 2-6 years after treatment) and was treated by repeated angioplasty in 5 of
these cases. Some centers in China have reported lower reocclusion rates with angioplasty and
primary stenting (29,30). We recommend periodic follow-up with Doppler ultrasonography or
venography following treatment in order to detect early reocclusion and for timely
reintervention.
Transjugular Intrahepatic Portosystemic Shunting

TIPS is used for treatment of BCS caused by diffuse HV thrombosis, with acute, subacute, or
chronic presentations (1, 2, 3, 4,31, 32, 33, 34, 35, 36) (Fig. 27-1). TIPS is also used in cases
of short-length HV obstruction in which angioplasty has failed (15).
Surgical portosystemic shunting has been widely used for Type I BCS to obtain decompression
of the hepatic sinusoids and relief of portal hypertension and its complications. TIPS has
become an alternative to surgical portosystemic shunting, as it has the following advantages: it
is less invasive; it can be used in patients with IVC occlusion due to compression by the
hypertrophied caudate lobe, which makes the surgical shunting more difficult to achieve; and it
does not preclude subsequent surgical shunting or liver transplantation (1).
In patients with Type I BCS, TIPS is created via the hepatic venous stump. If there is no
hepatic venous stump available, TIPS is created directly between the IH-IVC and the portal
system (Fig. 27-1). During such procedures, portal venography by injection of CO2 via a
catheter slightly advanced into the hepatic parenchyma may clearly demonstrate the portal vein
and make subsequent access to the portal branch easier (35).
After TIPS, patients are placed on intravenous heparin, until warfarin anticoagulation becomes
adequate (16). Patients receive periodic follow-up with Doppler ultrasonography, usually every
6 months, for detection of shunt stenosis.
As described above, TIPS creation in BCS patients is more difficult and hazardous than in
cirrhotic patients. However, the procedure appears to be successful in most of the attempted
patients, with few complications (31,32). According to four recent reports (31, 32, 33, 34),
which included 13 to 35 BCS patients, the technical success rates of TIPS creation ranged
from 92% to 100%, mortality rates ranged from 0% to 33% during the follow-up period of 2 to
4 years, and shunt stenosis developed in 33% to 87% of the procedures. The high incidence of
shunt stenosis is one problem with TIPS; however, the stenosis can be corrected by a second
intervention with angioplasty or restenting in most cases (15). Shunt stenosis does not
necessarily cause recurrent symptoms of BCS, perhaps because creation of the shunt allows
time for collateral circulation to develop (33). One study reported that the primary patency rate
of TIPS was significantly higher in BCS patients who received a PTFE (polytetrafluoroethylene)-
covered stent than in those who received bare stents (34).
In patients with fulminant BCS, TIPS has been used as a bridge to liver transplantation when a
donor is not immediately available (36). In such cases, optimal stent placement is important, as
a stent extending too far into the IH-IVC or the portal trunk may create difficulties during liver
transplantation (4).
As described previously, patients with Type I BCS at times have associated extrahepatic portal
vein thrombosis. In a report from the United Kingdom, 70% of such patients died despite liver
transplantation, surgical meso-atrial shunting, balloon angioplasty, or medical treatment (37).
These patients may benefit from TIPS, as this allows for direct mechanical disruption of the
portal vein thrombus and placement of stents in the affected portal vein if needed (38,39).
BUDD-CHIARI SYNDROME CAUSED BY INFERIOR VENA CAVA

OBSTRUCTION (TYPE II)
Obstruction of the IH-IVC is the most common cause of BCS in Asian countries and South
Africa (7, 8, 9,29,30). IVC obstruction commonly occurs in adults aged 20 to 60 years (8).
Males and females are almost equally affected. Doppler ultrasound,
MRI, CT, angiography, and percutaneous liver biopsy are useful to establish the diagnosis (1,3).
Anteroposterior and lateral projection angiograms obtained with simultaneous injection of
contrast material into the abdominal IVC and thoracic IVC have been used to evaluate the
extent of obstruction (Figs. 27-3, 27-4, 27-5 and 27-6).
FIGURE 27-3. Angioplasty for membranous obstruction of the hepatic IVC. A: Angiogram
(lateral view) obtained with simultaneous injection of contrast into the abdominal IVC and
thoracic IVC shows a membranous obstruction 2 mm thick. B: Radiograph during
angioplasty. The lesion was recanalized with the hard end of a guide wire and dilated by
simultaneous inflation of three balloons. C: Inferior vena cavogram immediately after the
procedure shows good blood flow through the dilated canal and retrograde filling of
contrast material into the right HV. D: Inferior vena cavogram obtained 3 weeks after
angioplasty shows good blood flow through the canal. An opacification defect (arrow) at
the hepatic IVC indicates abundant inflow from the right HV.
According to reports of surgical or histologic findings, the IVC obstruction is generally due to a
fibrous web of variable thickness, which is seen above or at the ostia of the main HVs
(8,40,41). This fibrous web is considered to result from the organization of prior IVC thrombosis
(7). The lesion is often associated with obstruction at the terminal parts of one or more main
HVs (8,40,41).
IVC obstruction has been divided into two subtypes, membranous (Fig. 27-3 and Fig. 27-6) and
segmental (Figs. 27-4 and 27-5), based on angiographic appearance. The membranous type
corresponds to a fibrous web. The segmental type is a long lesion measuring a few to several
centimeters. It seems to represent a fibrous web associated with luminal narrowing or
thrombosis below the web.
The clinical manifestations of IVC obstruction include the chronic form of BCS (hepatomegaly,
ascites, and esophageal
varices with near-normal liver function tests) and findings secondary to obstruction of the IVC
(swelling of the lower extremity and thoracoabdominal varicosity) (8,41) (Fig. 27-4).
Development of HCC is not rare in patients with IVC obstruction. The incidence of HCC in
patients with obstruction ranges from 4.7% to 41% in reports from Asian countries (7, 8,
9,41,42). The incidence was 47.5% in a report from South Africa (9).
FIGURE 27-4. Angioplasty for segmental obstruction of the hepatic IVC. A: Angiogram
(lateral view) obtained with simultaneous injection of contrast material into the abdominal
IVC and thoracic IVC shows a segmental obstruction 25 mm long. A large right inferior HV
(arrow) and caudate vein join the IVC just below the obstruction. B: Radiograph during
angioplasty. The lesion was recanalized with a laser device (46) and dilated with three
balloons. C: Inferior vena cavogram after angioplasty shows good blood flow through the
IVC. D: Contrast injection into the right inferior HV shows abundant collateral veins in the
right hepatic lobe. The proximal part of the right HV (arrowheads) is opacified via the
collaterals, and the terminal part of the vein shows occlusion. E, F: Photographs before (E)
and 3 weeks after (F) angioplasty show marked regression of thoraco-abdominal
varicosity after treatment.
Several surgical procedures, for example, transatrial disobliteration using a finger or catheter,
transcaval excision of the obstruction, bypass grafting, and transcaval posterocranial resection
of the liver (Senning's method), have been used for treatment of IVC obstruction (8,40,43).
These procedures usually require extracorporeal circulation, and reocclusion sometimes occurs
after treatment. Since the 1970s, percutaneous balloon angioplasty has been used for
correcting the lesion (44, 45, 46, 47, 48). This method is less invasive than surgery, but the
incidence of reocclusion is high. Since the late 1980s, metallic stents have been used to prevent
reocclusion after angioplasty (49). Metallic stents seem to be useful to obtain long-term
patency after angioplasty (29,30).
Okuda et al. studied 157 patients with BCS in Japan and reported on their prognosis (8). All but
9 patients had IVC obstruction; 114 of the 157 received surgical therapy or percutaneous
balloon angioplasty, while the others received only
medical therapy. The average period from the likely onset to the first medical consultation was
6.6 years, suggesting that most of the patients had a chronic course. Thirty-three patients died
during the follow-up period, with the main causes of death being hepatic failure, variceal
bleeding, and HCC.

Angioplasty and Stenting for Inferior Vena Cava Obstruction
(Type II BCS)
Percutaneous balloon angioplasty for treatment of IVC obstruction involves two steps:
recanalization of the obstruction and subsequent balloon dilation. Recanalization has been done
from a right femoral or jugular venous approach by advancing the hard end of a guide wire, a
Brockenbrough or other long needle, or even a laser device (29,30,44, 45, 46, 47, 48,50). This
step is sometimes difficult in cases of long segmental obstructions. Balloon dilation has been
done using a single large balloon (inflated diameter: 15 to 25 mm) or three or four medium-
sized balloons (inflated diameter: 8 or 10 mm). The use of multiple medium-sized balloons
allows for greater inflation pressures (>10 atm), though it may require multiple femoral or
jugular venous punctures.
Our method of angioplasty for treatment of membranous obstruction in recent years is as
follows (50): a sheath is inserted in the superior vena cava from a right jugular venous
approach. A 40-cm-long, 6-Fr catheter, reinforced with a 4-Fr stainless-steel cannula, is
introduced through the sheath into the superior vena cava. The catheter system has a small
bend 2 to 3 cm from the distal end. A target is created in the IVC just below the obstruction by
placing a catheter via the femoral vein. The distal end of the catheter system is directed to the
target under fluoroscopic observation. A 70-cm-long, 21-gauge hollow needle with a stylet,
originally developed by Matsui et al. for use in TIPS (51), is introduced through the system and
advanced until it reaches the target. After successful recanalization, the stylet is replaced by a
0.018-in. guide wire, the catheter is advanced into the IVC below the obstruction, a 0.035-in.
stiff guide wire is introduced through the catheter, and the catheter is replaced by a 6- or 7-Fr
balloon catheter (inflated diameter: 8 or 10 mm). After balloon dilation, two or three additional
balloon catheters are introduced via both femoral veins, and the lesion is further dilated by
simultaneously inflating the balloons. We prefer to cross to membranous obstructions from a
jugular venous approach because the lumen just below the obstruction is usually wider than that
just above it (Figs. 27-3a and 27-6b), and downward crossing avoids possible injury to the
heart (50).
Angioplasty for treatment of segmental obstruction has generally been done from a femoral
venous approach (29,30,45,50). Our method of angioplasty in recent years is as follows (Fig.
27-5): a sheath is inserted in the IVC from a right femoral venous approach. A 50-cm-long, 6-Fr
catheter, reinforced by a 4-Fr cannula, is introduced through the sheath to the IVC just below
the obstruction. The catheter system also has a small bend 2 to 3 cm from the distal end. A
target is created in the IVC just above the obstruction by placing a catheter through the jugular
vein. Under PA and lateral fluoroscopic observation, the tip of the catheter system is directed to
the lower end of the obstruction, and a guide wire is introduced through the system. The guide
wire and catheter system are gradually advanced upward through the obstruction with repeated
redirection toward a path of least resistance. The catheter system is advanced until it reaches
the upper portion of the obstruction and rests against the hard part of the lesion, which is
probably a fibrous web. The guide wire is replaced with a 70-cm long, 21-gauge needle, and
the hard part of the obstruction is recanalized by advancing the needle to the target placed in
the IVC above. If recanalization is unsuccessful, the upper target catheter is replaced by
another catheter-cannula system, a 70-cm-long, 21-gauge needle is introduced through the
system, and recanalization is performed by advancing the needle downward to the tip of the
catheter system below placed earlier. After successful recanalization, balloon dilation is done
with the same method as that used for membranous obstruction.
FIGURE 27-5. Angioplasty and stenting for segmental obstruction of the hepatic IVC. PA
(A) and lateral (B) angiograms obtained with simultaneous injection of contrast material
into the abdominal IVC and thoracic IVC show a segmental obstruction 5 cm long. The
right inferior HV (arrowheads) and caudate vein (arrow) join the IVC just below the
obstruction. C: Radiograph during recanalization. A 6-Fr catheter reinforced with a
stainless-steel cannula was advanced to the upper part of the obstruction from a femoral
venous approach. A 70-cm-long, 21-gauge needle (arrow) was introduced via the catheter
and advanced through the upper part of the lesion to the short thoracic segment of the
IVC. The thoracic IVC and right atrium are opacified by contrast. D: A 6-Fr catheter
reinforced with a cannula and a 70-cm-long, 21-gauge needle (arrow) used for
recanalization. E: Inferior vena cavogram after balloon dilation demonstrates good blood
flow through the hepatic IVC, which shows stenosis. F: The patient shows reocclusion 3
months after treatment. He received repeated balloon angioplasty and placement of
Gianturco stents. Inferior vena cavogram (lateral view) after stenting shows good blood
flow through the well-dilated IVC.
FIGURE 27-6. Membranous obstruction of the hepatic IVC with intraluminal thrombus. PA
(A) and lateral (B) angiograms obtained with simultaneous injection of contrast material
into the abdominal IVC and thoracic IVC show a membranous obstruction 3 mm thick and a
huge thrombus in the caudal IVC lumen. An attempt to dissolve the thrombus by regional
thrombolysis was unsuccessful. The lesion was recanalized with a laser device from a
jugular venous approach, and the hole was dilated with an 8-mm balloon (46). C: Inferior
vena cavogram (lateral view) after treatment shows antegrade blood flow through the
dilated hole (arrow). The patient was given oral antiplatelet drugs continually. D: Follow-up
cavogram obtained 3 months after treatment shows marked regression of the thrombus.
E: Follow-up cavogram obtained 10 months after treatment shows complete
disappearance of the thrombus. The hole has become larger due to the second dilation
with three balloons.
As described previously, the majority of segmental obstructions consist of a fibrous web and
luminal narrowing below the web. Based on this, we first advance the catheter system with a
guide wire to the upper portion of the long obstruction from a femoral venous approach and
then recanalize the hard part, presumably the web, with a needle (50). Segmental obstruction
has been recanalized from a femoral venous approach in most previous reports (29,30,45)we
suspect for reasons similar to ours.
The earlier experience with balloon angioplasty for membranous and/or segmental obstructions
indicates that angioplasty can safely correct the lesions. Although reocclusions often occur
(29,47, 48, 49), predominantly with segmental occlusions (48, 49, 50), they can be treated with
stents (49) (Fig. 27-5). Some centers have even started to perform primary stenting following
the initial balloon angioplasty (29,30). Gianturco stents have been used almost exclusively for
treating IVC obstructions because they are available in large diameters and their open structure
does not cause occlusion of the HVs when they are bridged (29,30,49). The Gianturco stents
generally used are 20 to 25 mm in diameter, and two or three stents in tandem connected by
struts.
Following balloon angioplasty and/or stenting, patients are given anticoagulant therapy with
heparin for a few days, followed by warfarin or oral antiplatelet drugs for several months
(29,30,45, 46, 47, 48, 49). Patients receive periodic follow-up with Doppler ultrasonography at
3- to 6-month intervals for early detection of restenosis (30).
Balloon angioplasty, with primary or secondary stenting, appears to be effective for treatment
of Type II BCS. We have performed balloon angioplasty in 18 patients with BCS: 10 patients
had membranous obstructions, and 8 had segmental obstructions 3 to 6 cm long. Angioplasty
was successful in all 18 patients, with few procedural complications. Seven (membranous, n =
6; segmental, n = 1) of the 18 did not show recurrence of symptoms during the follow-up period
of up to 19 years. In the other 11 (membranous, n = 4; segmental, n = 7), symptoms recurred
2 to 21 months after treatment, and subsequent examination showed reocclusion or severe
stenosis of the hepatic IVC. In 3 of the 11, balloon angioplasty was repeated four or five times
over periods of 3 to 6 years, and the IVC was kept open. The other eight received both repeat
angioplasty and stent placement (Gianturco) and did not show recurrent BCS during the follow-
up period of up to 8 years. In two recent reports from China (29,30), one with 32 and the other
with 85 patients with BCS caused by complete obstruction or stenosis of the hepatic IVC,
balloon angioplasty was performed with primary stenting. The procedure was successful in
93% to 97% of the patients, and the stent remained patent in the 96% to 97% of the patients
who had follow-up (n = 26 and 75, respectively) for up to 49 to 54 months. Reported
procedural complications were few, consisting of arrhythmia during balloon dilation (n = 2),
stent migration (n = 2), and pulmonary embolism (n = 1). The above outcomes are encouraging
and support the use of endovascular treatment.
As described previously, IVC obstructions, membranous or segmental, are often associated
with obstruction of one or more main HVs (8,40,41). If there is no patent large HV, angioplasty
of the IVC alone will not improve BCS, and thus additional angioplasty of the HVs will be
necessary (50). In our experience, however, all of the 18 patients who received angioplasty
showed disappearance of BCS within a few weeks after treatment, and in all of them
examination before or after the procedure demonstrated patency of one or more large HVs.
Namely, all of the 10 patients with membranous obstruction had a patent right HV that joined
the IVC just below the lesion (Fig. 27-3), and 6 of them also had a large inferior right HV (n = 5)
or caudate vein (n = 1) (52, 53, 54). All of the eight patients with segmental obstruction showed
complete occlusion of the right HV but had a large caudate vein (n = 8) and/or inferior right HV
(n = 6) that joined the IVC just below the long lesion (Figs. 27-4 and 27-5). Patency of one or
more large HVs and the presence of intrahepatic collateral circulation can explain the
improvement of BCS seen in our patients.
Membranous obstruction of the hepatic IVC is sometimes associated with a large thrombus in
the caudal IVC lumen. Such a thrombus is difficult to dissolve by systemic or regional
thrombolysisprobably because of the stagnant blood flow around it (46). We have
successfully treated four patients with membranous obstruction with such a thrombus (46,50)
(Fig. 27-6). In these patients, balloon angioplasty was performed to create a small hole, 5 to 7
mm in diameter, to establish antegrade blood flow around the thrombus. Oral anticoagulants
were given continually and the thrombus dissolved gradually, with no scintigraphic evidence of
pulmonary embolism. Angioplasty to create a small hole seems to be a good method for the
treatment of membranous obstruction associated with a large thrombus.
SUMMARY
BCS is caused by obstruction of the HVs or obstruction of the hepatic segment of the IVC. HV
obstruction is classified into two subtypes according to the affected site: diffuse thrombosis of
the HVs and short-length obstruction at the terminal part of the main HVs. IVC obstruction is
also divided into two subtypes, membranous and segmental, based on angiographic
appearance. Short-length HV obstruction and IVC obstruction of the membranous or segmental
type are treated with balloon angioplasty and primary or secondary stenting as needed. TIPS
has been used successfully in selected patients with BCS caused by diffuse HV thrombosis.
There are few reported clinical results for endovascular treatment of BCS, but most of them
are positive and encouraging. Further studies are necessary to better define the indications for
these procedures.
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33. Perello A, Garcia-Pagan JC, Gilabert R, et al. TIPS is a useful long-term derivative
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Transjugular Intrahepatic Portosystemic Shunts
Chapter 28
Transjugular Intrahepatic Portosystemic Shunts
Ziv J. Haskal
As with many medical advances, a groundbreaking concept long precedes the ability to realize
it. Nearly 20 years elapsed between Drs. Rosch and Hanafee's first report of creating canine
percutaneous portosystemic shunts in 1969 and its modern implementation in humans (1). In
1982, Colapinto et al. reported the first human application of the technique, using prolonged
balloon inflation in an attempt to create a durable liver shunt tract (2). It was not until 1988 that
the first human transjugular intrahepatic portosystemic shunt (TIPS) lined with a metal stent
was described (3). TIPS procedures rapidly evolved from lengthy ones requiring mapping
angiography, transhepatic targeting baskets, and other complex guidance tools into today's
routine TIPS, which may require less than an hour to complete. Thousands of TIPS have been
created to help treat the many complications of portal hypertension and more than 1,700
relevant scientific papers have been published. The current literature on TIPS is a mature one;
the number of prospective controlled trials involving TIPS exceeds that of endovascular
interventions in the superficial femoral artery.
TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT

FORMATION
The stereotypic TIPS is created in several steps: catheterizing and mapping a suitable hepatic
vein, typically the largest downgoing right hepatic vein; passing a long curved-tip needle from
within it into the liver parenchyma to puncture a branch of the intrahepatic portal vein; passing
catheters across this liver tract into the portal venous system, performing venograms and
hemodynamic assessments; dilating the parenchymal tract between the portal and the hepatic
vein; lining the tract and outflow hepatic vein with a stent-graft or stent; and progressively
dilatating these devices until the desired degree of partial portal decompression has been
achieved (Fig. 28-1).
There are many variations in the instrument sets, stents, and techniques used to fashion a
TIPS, though the basic principles remain the same. Most variations aim to make the portal vein
puncture easier or address anatomic abnormalities. Shunts can be created using fluoroscopic
guidance alone, combined external ultrasound (4), intravascular ultrasound guidance (5, 6, 7),
or computed tomography (CT) guidance (8,9), constructed directly from the inferior vena cava
(transcaval), created using a retrograde transmesenteric surgical approach (10,11), etc. Most
procedures are still performed using fluoroscopic guidance alone under conscious sedation and
require no more than an overnight stay in hospital.
CONTRAINDICATIONS
The contraindications to creating a TIPS can be classified as anatomic or physiologic. Relative
anatomic contraindications (i.e., ones that make TIPS formation more complex but do not
preclude it) include portal venous system thromboses, hepatic malignancies, polycystic liver
disease, and biliary obstruction. Physiologic contraindications include severely impaired hepatic
function or encephalopathy such that diversion of portal flow would lead to unacceptably
worsening liver function or failure; heart failure or pulmonary hypertension, or intracardiac
shunts that limit the ability to tolerate the increased cardiac output and work, or elevated atrial
pressures that follow any portosystemic shunt; and uncorrectable coagulopathies and, perhaps,
sepsis (12,13).
Prior to creation of an elective TIPS, patients with impaired hepatic synthetic function, e.g., with
elevated MELD scores, baseline encephalopathy, total serum bilirubin > 3 mg/dL, or cardiac
impairment or pulmonary hypertension, require careful consultations with referring hepatologists
and cardiologists so that all parties agree on the medical necessity of the procedure, the
possibility of accelerated liver transplant, strategies to optimize TIPS outcome, and, possibly, a
more conservative staged approach wherein a smaller shunt is created and possibly enlarged
further at a later date based on the patient's tolerance and symptomatic improvement.
INDICATIONS AND RESULTS

The ability to create TIPS to reduce portal venous pressures in a completely percutaneous
fashion has both vastly increased the indications and numbers of patients treated and
superseded open surgical portosystemic shunt formation. Among reported indications for TIPS
are acute uncontrolled or recurrent esophageal, gastric, or ectopic variceal bleeding, portal
gastropathy, refractory ascites, hepatic hydrothorax, Budd-Chiari syndrome (BCS), and
hepatorenal syndrome (HRS).
Acute Esophageal Variceal Bleeding Refractory to Medical

Treatment
Most actively bleeding esophageal varices, that is, acute bleeding, can be controlled by first-
line pharmacologic and/or endoscopic means using band ligation or injection sclerotherapy.
Failure of these treatments is an indication for portal decompression (or potentially accelerated
transplantation in appropriate candidates). Most reports of emergency surgical shunt creation in
the acute setting describe mortalities of 30% to
77% (14, 15, 16). One report of pooled data from 509 acutely bleeding patients treated with
TIPS described excellent control of variceal bleeding in 93.6% 6.7%, with an early rebleeding
rate of 12.4% 6.1%. Despite this, 35.8% 16% of patients died in hospital or within 6 weeks,
reflecting their severe comorbidities (e.g., liver failure, adult respiratory distress syndrome,
aspiration pneumonia, multi-organ failure) that plagues these critically ill patients (17).
Prognostic factors predicting survival after TIPS have been extensively studied. Significant ones
include MELD scores (13,18, 19, 20, 21, 22, 23, 24), Child-Pugh class or score (25), pre-TIPS
APACHE II scores (26, 27, 28, 29, 30), preprocedure total bilirubin (>3 mg/dL) (27), emergent
indications for TIPS, and endotracheal intubation (31,32). Thus salvage therapy with TIPS is
important in the acute setting but may not increase midterm survival in many of these severely ill
patients.
FIGURE 28-1. Diagrammatic representation of TIPS creation. A: The sheathed Colapinto

needle is advanced out of a hepatic vein into a portal vein branch. B: The parenchymal liver
tract is dilated using a balloon angioplasty catheter. C: The metallic stent is deployed within
the shunt tract.
Recurrent Esophageal Variceal Bleeding

Once an esophageal variceal hemorrhage has occurred, the risk of rebleeding is at least 50%.
Portal decompression, be it surgically or interventionally achieved, lowers rebleeding risks far
more than endoscopic treatments, though hepatic encephalopathy is almost always higher
(14,33,34). In meta-analyses of 376 and 811 patients, rebleeding rates for endoscopic
therapies were 49.8% and 46.6% vs. 12.4% and 18.9% for TIPS, respectively (14,34). More
than 12 randomized trials have compared secondary prevention of variceal bleeding using TIPS
or endoscopic sclerotherapy or band ligation (35, 36, 37, 38, 39, 40, 41, 42, 43, 44). In nine
trials, the median rebleeding rate for TIPS was 16%, versus 44% for endoscopic therapy.
Survival was rarely improved (41), emphasizing the progressive nature of advanced liver
disease and the need for transplant evaluation.
There is no evidence to support the use of TIPS for primary prophylaxis of variceal bleeding,
that is, at initial diagnosis of varices but prior to any bleeding. TIPS has been compared to
medical therapy in a small number of patients. In one series of 91 patients followed for 2 years,
the risk of rebleeding was 39% for those treated with pharmacologic therapy, versus 13% for
those receiving a TIPS (45). Encephalopathy developed in 14% of those receiving drugs and
38% of TIPS patients. Child-Pugh class improved in 72% of the drug group but in only 45% of
the TIPS group. The 2-year probability of survival was the same in both groups, 72%. The cost
of therapy in the TIPS group was twice that in the medical group (45). Of note, in some of the
trials, the patients were medical failures, whereas in others they had a single index bleed
before randomization. Until controlled trials establish otherwise, primary prophylaxis should
be achieved by medical therapy and, occasionally, endoscopic means.
Gastric Varices
TIPS has proven efficacious for controlling gastric variceal bleeding in multiple nonrandomized
trials (46, 47, 48, 49, 50). It appears that TIPS is equally effective in controlling gastric and
esophageal variceal bleeding. The place for controlled trials may be comparing endoscopic glue
injections versus TIPS for acute or recurrent gastric variceal bleeding. In the author's opinion,
TIPS is extremely useful for control of gastric variceal bleeding, though procedural end points
can be different from those for esophageal varices. Lower final gradients may be needed
and/or combined with aggressive transcatheter sclerosis of varices and embolization. Another
alternative to TIPS and embolization of gastric varices is balloon occluded retrograde
transvenous obliteration (51, 52, 53, 54, 55). This technique, pioneered in Japan, involves
retrograde catheterization of the gastric variceal outflow into the left renal vein, isolation of
collateral veins (e.g., phrenic and lumbar veins by embolization), and endovascular
sclerotherapy of the gastric varices. One 20-patient trial comparing endoscopic sclerotherapy
to transvenous obliteration reported results mimicking those with endoscopic therapy using
fewer sclerosants. In another, 1-year follow-up, endoscopies revealed variceal decrease or
disappearance in 81% of patients. Some authors have suggested that portal perfusion and liver
function can be improved by occlusion of competing splenorenal shunts in such patients (56).
Ectopic Varices
Duodenal, intestinal, stomal, and anorectal varices are relatively uncommon but appear to
respond well to TIPS and possible adjunctive embolization (57, 58, 59, 60, 61, 62, 63, 64, 65,
66, 67, 68, 69, 70, 71, 72, 73). It is worth emphasizing the need for clinical suspicion of
intestinal varices in patients with liver disease and occult lower gastrointestinal bleeding.
Diagnostic visceral angiography (with careful attention to the venous phase) should be
considered, as CT or MRI can miss the varices. These varices often develop within adhesions
related to prior abdominal surgery and decompress into alternative pathways, such as through
the gonadal or ovarian veins.
Portal Hypertensive Gastropathy (PHG) and Gastric Antral

Vascular Ectasia (GAVE)
These two entities are different yet can coexist and be difficult to differentiate during
endoscopy. The mucosa in gastropathy reveals a mosaiclike pattern, usually within the fundus
or body of the stomach. In contrast, GAVE is typified by linear or diffuse red patches within the
stomach antrum. PHG is related to portal hypertension, while GAVE can be seen in an
assortment of conditions (74). The use of TIPS in patients with PHG and GAVE has been
described in a number of reports (75, 76, 77, 78, 79, 80). In one report 75% of patients with
severe PHG showed both endoscopic improvement and a decrease in the need for transfusions
(80). In another series, 9 of 10 patients showed endoscopic improvement in PHG following
TIPS (81). In contrast, bleeding from GAVE in patients with cirrhosis was unaffected by TIPS.
In the author's experience, TIPS is very useful in controlling blood loss due to portal
gastropathy or similar intestinopathies within the duodenum or small bowel. Accordingly, GAVE
is best treated with endoscopic ablation using lasers, argon plasma coagulation, or heater
probes.
Refractory Ascites
Ascites is considered refractory to medical treatment when it is unresponsive to or intolerant of
sodium restriction and high doses of diuretics (400 mg/day spironolactone and 160 g/day
furosemide) (82). Once truly refractory ascites develops, approximately 50% of patients die
within 12 months (without transplant rescue) (83). Controlled trials have shown that TIPS
clearly reduces the incidence of cirrhotic ascites, the amounts of diuretic used, and the number
of large-volume paracenteses (LVP) required. Pooled results from four controlled trials (264
patients) demonstrated a mean ascites improvement in 57.8% for TIPS, compared with 19%
for LVP (84, 85, 86, 87). Encephalopathy was more frequent in the TIPS groups, 34.0
19.8%, compared to the LVP groups, 18.5 12.0%. A transplantfree survival benefit for TIPS
was seen in one trial (85) but not another (86). Overall survival was not improved in the latter
(NASTRA) trial, though a 6-month mean survival difference was seen in the TIPS patients
arguably noteworthy in a population in whom survival without transplantation may be measured
in months.
One prospective controlled study compared TIPS with pleuroperitoneal (Denver) shunts for
treatment of refractory ascites (88). Primary median shunt patencies were similar (TIPS, 4.4
months; Denver shunt, 4.0 months), though assisted patencies were 31 months for TIPS,
compared with 13 months for Denver shunts. Survival in the TIPS groups was also longer, 28.7
versus16 months. These findings support the use of TIPS in ascites patients who can tolerate
portal decompression (Fig. 28-2).
Refractory Hepatic Hydrothorax

Hepatic hydrothorax occurs in approximately 5% of cirrhotics. Hepatic hydrothorax can develop
in patients with or without detectable cirrhotic ascites due to passage of ascitic fluid from the
abdominal cavity through diaphragmatic pores. TIPS has proven relatively uniformly successful
at resolving or markedly reducing hepatic hydrothoraces (89, 90, 91, 92, 93, 94, 95, 96). When
diuresis fails, TIPS provides important next-line care for these patients, as other alternatives
are imperfect and few (e.g., pleuroperitoneal shunts and tunneled chronic pleural drainage
catheters).
Hepatorenal Syndrome
Type 1 HRS is a rapidly progressive form of renal failure with extremely high nontransplant
mortality rates. In contrast, Type 2 HRS brings a slower, progressive onset of renal failure
(97,98). Reports of TIPS in HRS patients describe improved glomerular filtration rates, renal
plasma flow, and urine sodium handling and drops in serum creatinine and plasma aldosterone
(99, 100, 101, 102, 103, 104, 105, 106). While survival in Type I HRS after TIPS appears to be
improved compared with historical expectations, none of the trials were randomized. In one
series, only 20% of the patients with Type 1 HRS were alive 1 year after TIPS insertion,
whereas approximately 45% of those with Type 2 HRS were alive after 1 year (99,106). In the
four controlled trials in which TIPS was compared to LVP in the control of refractory cirrhotic
ascites discussed above, there was no consistent improvement in renal function with TIPS
compared to LVP, although one study did find a reduced incidence of HRS in those receiving a
TIPS (86). Ultimately, TIPS should be compared to newer potential therapies such as
terlipressin before a widespread role is recommended (107).
FIGURE 28-2. TIPS placement in an elderly patient with refractory ascites. A: Initial
hepatic venography demonstrates a large patent right hepatic vein. B: Initial transjugular
splenic venography demonstrates hepatopetal portal and splenic vein flow. The
portosystemic gradient was 19 mm Hg. C: After tract dilatation, parenchymal tract
venography is performed using a measuring catheter. The portal (PV), parenchymal tract
(T), and outflow hepatic vein (HV) are seen. D: Transjugular portogram after deployment of
a 10-mm-diameter Viatorr TIPS endograft. The portal end of the stent was left intentionally
undilated (to reduce potential encephalopathy while assessing the effect on the patient's
ascites). Clinical follow-up within the first 2 weeks demonstrated spontaneous diuresis of
the ascites. The final portosystemic gradient was 9 mm Hg.
Budd-Chiari Syndrome
BCS, arguably better termed hepatic outflow block, results from blockage of exit of the blood
from the liver due to either hepatic vein thrombosis or obstruction of the inferior vena cava
(108,109). Liver injury, fibrosis, and cirrhosis result from unremitting hepatic congestion, a
condition unmitigated by anticoagulation. Surgical shunts have long proven useful in preventing
or stabilizing liver disease in BCS patients, though their prothrombotic tendencies and caval
compression (by the congested swollen liver) have required more extensive surgeries, including
mesoatrial shunts. Numerous case series (110, 111, 112, 113, 114, 115, 116, 117, 118, 119,
120, 121, 122, 123, 124, 125, 126, 127, 128) have described beneficial use of TIPS in acute
and chronic BCS.
A greater need for reinterventions has been reported in BCS patients undergoing TIPS
(122,129), likely related to underlying hypercoagulability or anatomic issues related to the TIPS.
In the author's 14-year experience treating acute and chronic BCS patients with TIPS, the
technical challenges of TIPS in BCS can be significant and warrant variation from conventional
techniques, including the use of external ultrasound, coaxial fine needles, or intravascular
ultrasound (Fig. 28-3). The author anticoagulates all BCS TIPS patients because of their
presumed or proven underlying coagulopathy and performs periodic transjugular biopsies to
confirm continued prophylaxis against recurrent hepatic congestion and development of fibrosis.
COMPLICATIONS
The potential technical complications of TIPS are numerous, although, in experienced hands,
they should be very infrequent. As some of its steps mimic those of a transhepatic liver biopsy
(performed in a cephalocaudal direction), similar liver injury can occur, particularly with
prolonged attempts at puncturing the portal vein. Indeed, it is arguable that, unless one
maintains a regular competency in shunt formation, that elective procedures be referred to
experienced centers to reduce risks of liver injury and the patient radiation dose that can
accompany a lengthy procedure. The Society of Interventional Radiology TIPS Quality
Improvement document describes a list of the more common important complications, dividing
them into major and minor severities, with the following incidences for each (130):
Minor complications (4%): transient contrast induced renal failure, 2%; encephalopathy
controlled by medical therapy, 15% to 25%; fever, 2%; transient pulmonary edema, 1%;
entry site hematoma, 2%.
Major complications (3%): hemoperitoneum, 0.5%; gallbladder puncture, 1%; stent
malposition, 1%; hemobilia, 2%; radiation skin burn, 0.1%; hepatic infarction, 0.5%; renal
failure requiring chronic dialysis, 0. 25%; hepatic artery injury, 1%.
Mortality rates attributable to intraprocedural complications should not exceed 1%. The
reported incidence of new or worsened encephalopathy ranges from 15% to 31% and largely
depends on the severity of preexisting liver disease and encephalopathy (131, 132, 133).
Patients treated for refractory ascites or hydrothorax often have more baseline encephalopathy
and worse liver function than patients with variceal hemorrhage and, thus, may carry greater
risks of further encephalopathy after TIPS. Naturally, controlled trials have shown higher
encephalopathy rates in TIPS patients compared to those treated with LVP, endoscopic
sclerotherapy, or band ligation. With proper patient selection, postprocedure encephalopathy
therapy, and judicious initial creation of smaller shunts in higher-risk patients, shunt reduction or
intentional occlusion is rarely needed (134, 135, 136, 137, 138, 139). Prudence is warranted
when intentionally occluding a shunt, as HRS after shunt occlusion has been reported (140).
SHUNT PATENCY
As TIPS use became widespread in the 1990s, it became clear that stenoses and occlusions
developed unpredictably and frequently, though recurrent symptoms did not necessarily follow.
Reported rates of TIPS dysfunction range from18% to 78% (35,38, 39, 40,42, 43, 44,141); the
wide range of values reflects the differences in surveillance tools, intervals, and definitions.
Doppler sonography is the most commonly used tool for assessing shunt patency (142, 143,
144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161,
162, 163). The early TIPS sonography papers described very high ultrasound diagnostic
accuracies but were plagued by inconsistent or undefined patency definitions, lack of
comparisons with catheter venography, and, arguably, lack of clinically useful definitions of
patency (i.e., return of portal hypertension). Later, larger studies were methodologically flawed
because sonographic criteria of shunt dysfunction were used to trigger gold standard
venographic validation of the sonographic diagnosis. Stated another way, when no TIPS
abnormality was suggested by TIPS sonography, then no confirming venography was
performed (156,164). TIPS sonography is, by nature, limited because measured velocities
loosely correlate with percentage shunt stenosis, and percentage shunt stenosis loosely
correlates with recurrent (and unacceptable) elevations in portal pressure (165).
One prospective study compared 151 Doppler sonograms with invasive TIPS venography and
portal pressure measurements. Using a success or failure definition of a portosystemic gradient
of <15 or 15 mm Hg, respectively, sonography provided a sensitivity and specificity of only
86% and 48%, respectively (155). Thus, an abnormal Doppler ultrasound is predictive of
occlusion or stenosis, whereas a normal ultrasound does not exclude TIPS dysfunction
(155,160,166, 167, 168, 169). Ultimately, though, the marked improvement in shunt patency
provided by expanded polytetrafluoroethylene (ePTFE) TIPS stentgrafts makes the diagnostic
accuracy of TIPS sonography less critical.
Improving Transjugular Intrahepatic Portosystemic Shunt
Patency: The Use of Stent-Grafts
In 1995, Nishimine et al. published the first animal investigation evaluating the efficacy of
covered stents for TIPS (170). They compared the results of 13 swine TIPS lined with bare
stents with those of 13 swine TIPS lined with handmade PTFE stent-grafts. At 4 weeks, 1
control TIPS was patent (8%), whereas 9 of 13 (69%) PTFE stent-grafts demonstrated a
stenosis of <50%. By 3 months, six of the 13 stent-grafts remained patent (defined as <50%
shunt stenosis). In five cases, hepatic vein stenoses contributed to loss of graft patency. In
1997, these results were expanded on using an encapsulated ePTFE stentgraft designed
specifically for TIPS (171). Eight TIPS were created in eight pigs using this stent-graft. All but
one of the shunts were patent at 1-, 3-, 4-, and 5-month explant and venography. In contrast,
the Wallstent control group developed occlusions or stenoses of 45% to 85% within 4 weeks.
The observed histologic responses mimicked those of humans.
Saxon et al. published the results of an important human pilot study evaluating stent-grafts for
revisions of TIPS stenoses and occlusions (172). Six patients with an initial mean primary TIPS
patency of 50 days (range, 9-100 days) had their TIPS lined with a modified Z-stent
endoskeleton supporting a 4-mm Gore PTFE graft (W. L. Gore and Associates, Flagstaff, AZ)
that had been dilated to 14 mm in diameter. Three patients had initially demonstrable biliary-to-
TIPS fistulae, a recognized cause of early shunt thrombosis. Of five surviving patients, three
remained patent at a mean venographic follow-up of 315 days. One shunt occluded and one
became stenotic due to graft misplacement. The authors concluded that PTFE-covered
stentgrafts were effective for revision of TIPS in patients with tract stenosis and occlusion.
Expanding on the promising results of animal and pilot human studies with PTFE, numerous
case reports and series reporting patency improvements with homemade PTFE TIPS stent-
grafts appeared (5,173, 174, 175, 176, 177, 178). In 2000, the Viatorr TIPS endoprosthesis
(W. L. Gore and Associates) became available in Europe. Since then, several thousand TIPS
stent-grafts have been implanted for de novo or revision applications and reports of outcomes
are rapidly appearing in publication (179, 180, 181, 182, 183, 184, 185, 186, 187). In one
series typifying the results described in other retrospective Viatorr series, Hausegger et al.
reported primary patencies of 87% and 80% at 6 and 12 months, respectively, using
sonographic or venographic criteria (184). Notably, the mean initial post-TIPS pressure gradient
of 6 mm Hg was almost unchanged in those patients undergoing 6-month venography
arguably one of the most critical end points in shunt function. In a retrospective case-matched
series of bare stent TIPS versus stent-grafts, Angermayr et al. reported statistically significant
survival improvements in patients receiving PTFE grafts (181).
FIGURE 28-3. TIPS creation in a young patient with chronic Budd-Chiari syndrome,
ascites, and severe leg swelling. A: Inferior vena cava venography demonstrates marked
narrowing within its intrahepatic portion. The caval gradient was 24 mm Hg. B: Transcaval
catheterization of the right portal vein was performed under combined fluoroscopic and
intravascular ultrasound (IVUS) guidance. The IVUS catheter is visible (I). C: Initial portal
venography demonstrates hepatofugal portal flow. Reversed flow in the inferior mesenteric
vein is seen. The initial portal vein pressure was 59 mm Hg. The portosystemic gradient
was 46 mm Hg. Extraordinarily high gradients are often seen in patients with Budd-Chiari
syndrome. D: Portal venography after TIPS formation demonstrates decompressive flow
into the narrowed vena cava. The TIPS was created using a Viatorr stent-graft within the
parenchyma and a coaxial Wallstent extending into the inferior vena cava (so as not to
occlude the IVC with a covered stent). The final gradient was 8 mm Hg. Sixteen-millimeter
balloon angioplasty of the suprahepatic inferior vena cava downstream of the TIPS. E: One
year later, the patient returned with recurrent ascites and leg swelling. An IVC balloon
expandable stent was placed. At 4-month follow-up, her ascites remained resolved, as did
her leg swelling.
In 2004, the 253-patient U.S. multicenter randomized trial comparing TIPS created with the
Viatorr stent-graft and Wallstents was completed. As its principal investigator, this author
reports that freedom from the need for repeat interventions and shunt patency were markedly
better in the stent-graft group (p = 0.007). At 6-month venography, the percentage diameter
TIPS stenosis was significantly lower in the Viatorr group (16% vs. 42%; p <0.001), as were
follow-up portosystemic gradients (Fig. 28-4). There was only one Viatorr patency loss due to
diameter stenosis >50%, occurring in an unstented hepatic vein. In contrast, 11 Wallstent
patency losses occurred, a 10-fold higher incidence. By Kaplan-Meyer analysis, the time to
reinterventions was also significantly shorter in the Wallstent group (p = 0.007). Encephalopathy
and serious adverse events were not significantly different among the groups. As such, TIPS
stent-grafts mark a major step in TIPS evolution, by providing the out-of-the-gate durability that
was lacking in bare stents. Studies comparing TIPS, endoscopic therapies, and surgery may
require repetition, and controlled trials of smaller-caliber shunts may prove useful in select
populations by minimizing the negative effects of portal decompression on liver perfusion.
FIGURE 28-4. Fourteen-month explant of a Viatorr-lined TIPS at liver transplantation.

Hematoxylin and eosin-stained, high-magnification, cross-sectional image demonstrates
nearly no tissue encroachment on the graft-lined shunt lumen (L). The
polytetrafluoroethylene graft is indicated by the white asterisk. The black circle is a
transected metal strut of the stent-graft.
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Balloon-Occluded Retrograde Transvenous Obliteration in Portal Hypertension
Chapter 29
Balloon-Occluded Retrograde Transvenous
Obliteration in Portal Hypertension
Shozo Hirota
Kaoru Kobayashi
Hiroaki Maeda
Satoshi Yamamoto
Norio Nakao
The number of patients with viral hepatitis and liver cirrhosis exceeds 3 million in the United
States, and how to deal with esophageal and gastric varices caused by portal hypertension
(PH) accompanying viral hepatitis and liver cirrhosis has become an important issue (1).
There are four therapeutic approaches for PH: endoscopic treatment, surgery, interventional
radiology, and conservative treatment. In recent years, interventional radiology has become
important because it extends the therapeutic options to include percutaneous transhepatic
obliteration of varices (2,3), partial splenic embolization (4), and, of course, transjugular
intrahepatic portosystemic shunt (5). In Japan, on the other hand, balloon-occluded retrograde
transvenous obliteration (B-RTO) (6, 7, 8, 9, 10, 11, 12) was developed in 1996 as a
transcatheter treatment for gastric varices that were difficult to treat by endoscopic injection
sclerotherapy, and the beneficial therapeutic effect has been proven over the last 10 years. In
this chapter, we describe the treatment rationale, therapeutic technique, and results for B-RTO.
HEMODYNAMICS OF GASTRIC VARICES AND BALLOON-

OCCLUDED RETROGRADE TRANSVENOUS OBLITERATION
The supply routes for gastroesophageal varices are the left gastric vein and short/posterior
gastric vein (Fig. 29-1). The former is the major route for esophageal varices, and the latter is
the major route for gastric varices. The blood that pours into the gastric varices on the posterior
wall of the gastric fornix descends to flow from the inferior phrenic vein into the renal vein via
the adrenal vein. This is called the gastrorenal (GR) shunt. In the ascending route, on the other
hand, the blood joins the flow in the pericardial vein to pour into the inferior vena cava just
above the left hepatic vein.
Because a large volume of blood flows quickly in gastric varices, mortality due to rupture is
high. These varices are located in the fornix, so it is not easy to perform endoscopic
hemostasis treatment.
With B-RTO, a balloon catheter is placed retrogradely in the GR shunt or the inferior phrenic
vein flowing into the inferior vena cava so that sclerosant can be injected into the gastric varices
for thrombus formation while the blood flow is cut off. For indications and contraindications, see
Table 29-1.
PREOPERATIVE PROCEDURES
The GR shunt should be thoroughly examined by CT (Fig. 29-2). The left inferior phrenic vein
may be seen on the CT scan and the hemodynamics should be clear.
Gastric varices are classified according to endoscopic findings into three types: Lg-c, which
refers to gastric varices located at the cardiac ring; Lg-cf, which refers to gastric varices that
continue from the cardiac ring to the gastric fornix; and Lg-f, which refers to isolated gastric
varices found in the fornix, apart from the cardiac ring. Hemodynamically, the short gastric vein
and posterior gastric vein are the supply routes for Lg-f and flow into the GS shunt. B-RTO is
most suitable for the Lg-f type but is performed on the Lg-cf type also.
Preparation of Drugs
Ethanolamine oleate (EO) is a sclerosant used for varices (13). One vial of EO (Oldamin; 10
mg/vial; Takeda Chemical Industries, Ltd.) is dissolved in 10 mL of nonionic contrast medium to
prepare a 5% EO injection (EOI). The maximum single dose of a 5% EOI is 20 mL. Absolute
ethanol is used concomitantly to occlude the small collateral veins or when the amount of EOI
exceeds the maximum single dose used for large varices.
Haptoglobin (Mitsubishi Pharma Corp.) is used to prevent renal failure due to hemolysis
attributable to the red cell membrane destroyed by EOI; 4,000 units is injected intravenously
both preoperatively and perioperatively (14). Haptoglobin is a therapeutic agent for
hemoglobinemia and hemoglobinuria due to hemolytic reaction, and 1 U combines with 1 mg
hemoglobin.
Catheters
A 6-Fr occlusion balloon catheter (Clinical Supply Co., Gifu, Japan) with a balloon diameter of
20 mm and balloon length of 20 mm is frequently used. A balloon diameter of 10 mm is
required (Fig. 29-3). Other devices that are employed include an 8-Fr guiding sheath (Medikit
Co., Tokyo), a 2.3-Fr microcatheter (Prowler Plus; Johnson & Johnson, Miami, FL), and a 2.7-
Fr microcatheter (Progreat; Terumo, Tokyo).
PROCEDURE
Angiography of the superior mesenteric and celiac arteries is performed to reaffirm the
hemodynamics. Prostaglandin is used
for visualizing the portal system during superior mesenteric angiography. Angiography is
performed via the left femoral artery because the right groin is used for the venous access.
FIGURE 29-1. Hemodynamics of the gastric fundal varices and collateral veins. Ad V,
adrenal vein; BC, balloon catheter; CV, coronary vein; Ip V, inferior phrenic vein; IVC,
inferior vena cava; G-R, gastrorenal; GV, gastric varices; Pc V, pericardiacophrenic vein;
PGV, posterior gastric vein; PV, portal vein; RV, renal vein; SGV, short gastric vein; Sp V,
splenic vein.
The two approaches for catheter insertion into the GR shunt are femoral and jugular veins. An
8-Fr guiding sheath is inserted from the right femoral vein into the GR shunt. A commonly used
multipurpose 6-Fr balloon catheter with a slight angle is inserted into the GR shunt to perform
angiography under balloon occlusion. A wedge catheter facilitates the procedure and requires
less EOI (downgrading technique) (10) (Fig. 29-4).
Angiography under balloon occlusion of the GR shunt reveals many collateral veins (Fig. 29-5).
The inferior phrenic vein is the largest, and the pericardial vein is frequently dilated in the
angiographic images. The ascending lumbar vein and small veins of the accessory hemiazygos
vein system often become the collateral veins. Sclerosant injected in these circumstances does
not flow into the gastric varices but drains into the inferior vena cava and the azygos venous
system from the collateral veins. Therefore, it is necessary to occlude the collateral veins
carefully. We grade the collateral veins and occlude the collateral veins accordingly (see Fig.
29-6 for grading of the collateral veins) (7). Grade 1 and 2 collateral veins rarely need
occlusion, but veins of grade 3 and higher require occlusion. For grade 4 or 5, concomitant use
of a balloon catheter that is inserted into the left gastric vein under percutaneous transhepatic
portography to stop the blood flow can be adopted.
TABLE 29-1 INDICATIONS AND CONTRAINDICATIONS FOR B-RTO
Indications
Emergency cases of gastric varices with rupture and cases of gastric varices with

a history of rupture or in danger of rupture that have a GR shunt
Cases with hepatic encephalopathy due to a GR shunt
Relative indications
Hepatic encephalopathy due to portosystemic shuntattributable to mesocaval

shunt, etc.
Bleeding: venous shunt attributable to portal hypertension such as duodenal

varices and mesenteric varices
Relative contraindications
Cases in which contrast agent flows easily from the shunt into the portal vein. B-
RTO is not indicated for these cases because the sclerosant, i.e., an embolizing
agent, may drain into the portal system.
Contrast x-ray examination of the shunt is performed under balloon occlusion to grade the
development of collateral veins and the gastric varices (7). In grade 1, only the gastric varices
are opacified (Fig. 29-7). In grade 2, many gastric varices as well as the inferior phrenic veins
and some small veins are depicted and the contrast medium does not wash out immediately. In
grade 3, more collateral veins are seen than in grade 2, and the gastric varices are only
partially depicted (Fig. 29-8). In grade 4, only the collateral veins are depicted, and the gastric
varices are not opacified (Fig. 29-9). In grade 5, the GR shunt shows dilation exceeding 30
mm, and the balloon catheter is swept away by the flow of blood into the renal vein.
For grade 1, the collateral veins can be occluded by EOI alone. As the grade progresses from
2 to 4, however, small amounts of ethanol, metal coil, etc., are required. For grades 2 to 4, the
downgrading technique is performed once, and if this is successful, less or no occlusion of the
collateral veins is required. For downgrading, a 2.7-Fr microcatheter (Progreat; Terumo) is
advanced with use of the attached microwire through the previously introduced balloon catheter,
going past as many collateral vessels as possible and finding a position close to the main
variceal body. This microcatheter with attached microwire is then used to attempt selective
catheterization of the varices. Next a 6-Fr balloon catheter is carefully advanced through the
GR shunt into the gastric varices or into the GR shunt just distal to the varices. With this
technique, gastric varices are entirely opacified without evidence of collateral veins. A 0.035-in.
hydrophilic guide wire (Radifocus; Terumo) is occasionally employed. Fukuda et al. (10)
reported that 13 of 15 patients with gastric varices of grade 3 were successfully downgraded
with this technique.
When a catheter cannot be inserted from the inferior vena cava into the inferior phrenic vein
with grade 4 varices, as many of the collateral veins as possible are occluded with ethanol or
coils by using a microcatheter. The balloon is then inflated in the GR shunt to inject a small
amount of absolute ethanol and ~20 ml of 5% EOI. The EOI drains into the remaining small
collateral veins in a short period, but the number of collateral veins is markedly decreased, and
the B-RTO procedure is easier when it is performed again 1 or 2 weeks later. In some cases
with grade 5 varices, percutaneous transhepatic insertion of a balloon catheter into the left
gastric vein is needed due to the high flow of blood, while inserting another balloon catheter into
the left adrenal vein by the usual method to perform B-RTO by obstructing both veins.
Injection of Ethanolamine Oleate

Injection of EOI can surely be performed without excessive venous occlusion if a microcatheter
is superselectively inserted from inside the balloon catheter into the gastric varices to inject or
fill EOI. We have set the maximum injection volume of EOI
at 30 mL (7). The gastric varices are opacified by the imaging ability of EOI. Embolization of
varices can be fully expected if EOI is not injected until the gastric varices is depicted.
FIGURE 29-2. Contrast-enhanced three-dimensional reconstructed CT of a 68-year-old

woman with gastric varices showing huge gastric varices (A) and gastrorenal shunt (B)
(arrow) clearly. We can diagnose hemodynamics of varices preoperatively.
After injection EOI, the catheter is placed for 5 hours under balloon occlusion. When B-RTO is
started in the afternoon and completed in the evening, the patient returns to his or her room,
and the catheter remains in place until the following morning. Angiography is performed for
confirmation the following morning in the angiography room, and the balloon is deflated and
removed. When the balloon occlusion time is short, the thrombus in the gastric varices or the
GR shunt may move to cause severe pulmonary embolization. Some medical facilities, including
ours, leave the catheter in place until the following morning.
FIGURE 29-3. A long introducer sheath and a balloon catheter 20 mm in diameter. An 8-Fr
introducer with inverted S curve (A) is inserted into the adrenal vein, then a 6-Fr balloon
catheter (B) is placed via the long sheath in the distal side of the gastrorenal shunt. (See
the color insert.)
FIGURE 29-4. Downgrading technique. A: A 65-year-old man with chronic hepatitis had
large gastric varices. Portography via superior mesenteric artery demonstrated huge
gastric varices draining from the left gastric vein. B: After an 8-Fr introducer sheath was
inserted from the right femoral vein and wedged into the left adrenal vein, a 6-Fr balloon
catheter was placed in the distal side of the gastroduodenal shunt. Balloon-occluded
retrograde left adrenal venography showed the inferior phrenic vein and many collateral
veins, without depiction of gastric varices. These were classified as grade 3 varices. C:
The 6-Fr balloon catheter was then carefully advanced through the gastrorenal shunt into
the gastric varices. Retrograde venography under balloon occlusion showed gastric varices
without evidence of collateral veins. D: Schema of the downgrading technique. Before
downgrading, contrast medium drains into small collateral veins, without depiction of
gastric varices. After superselective insertion of the catheter into the gastric varices,
gastric varices are well shown.
CLINICAL RESULTS
Of 145 patients who underwent B-RTO (12), the technical success rate was 93%. (Success
was defined as the disappearance or marked reduction of the varices after a single or repeated
B-RTO procedures.) Other studies reported 95% to 100% success rates (6, 7, 8) but were
based on data sets smaller than in our study.
Thirteen of 14 patients (93%) showed improvement in the encephalopathy. Shunt-related
hepatic encephalopathy due to increased shunt blood flow can be dramatically improved by
closing the shunt via B-RTO if the GR shunt is the primary shunt (6,7). In many cases, however,
many other shunts exist, and mild hepatic encephalopathy may remain when only the GR shunt
is closed. In these cases, it is necessary to consider closing the other shunts.
Approximately 25% to 40% of esophageal varices may require endoscopic treatment (8). Of
the Lg-cf type, gastric varices are thought to be worse when the flow is from the left gastric
vein to the esophageal vein.
The increased portal blood flow improves the hepatic function reserve. In this study, 48% (44 of
91 patients) showed an improvement in liver function. Clinical improvement in liver function
reserve is defined as a decrease in the Child-Pugh score. B-RTO occludes the shunt, which
causes an increase in portal pressure. At the same time, the diverted blood flows toward the
liver, and the increased hepatopetal flow improves the hepatic function reserve. This is thought
to induce the improvement in liver function. Because the hepatic volume is increased after B-
RTO, B-RTO is expected to be a therapeutic measure for liver cirrhosis. Liver cancer, which is
known to be a prognostic factor (8), was seen in 42 cases.
FIGURE 29-5. A 58-year-old woman had large gastric varices diagnosed as grade 1. A:
Preprocedural portal venography via the superior mesenteric artery showed gastric varices
draining from the left gastric vein. B: Venous phase of celiac arteriography also showed
both gastric varices draining from the short gastric vein to the gastrorenal shunt (arrow). C:
A 6-Fr balloon catheter was then carefully advanced into the gastrorenal shunt. Retrograde
venography was performed under balloon occlusion of the gastrorenal shunt. The large
dilated tortuous varices are depicted. Then 20 mL of EO was injected. The balloon
catheter and guiding sheath were placed with the balloon catheter inflated until the next
day. D: The next morning, retrograde venography with hand injection with a small amount
of contrast medium demonstrated complete obstruction of the gastric varices. E:
Gastrofiberscopy shows very large dilated gastric varices at the fornix before B-RTO. F:
Dilated gastric varices had almost disappeared 3 months after the procedure. (See the
color insert.)
FIGURE 29-6. Diagrams of the grades of progression of gastric varices and collateral
veins: grade 1, gastric varices are well opacified, without evidence of collateral veins;
grade 2, collateral veins are small and few in number, and the contrast medium remains in
the gastric varices for 3 minutes; grade 3, collateral veins are medium to large, there are
few veins, and the contrast medium fills the gastric varices only partially and disappears
within 3 minutes; grade 4, there are many large collateral veins, and the gastric varices are
not opacified; and grade 5, the left adrenal vein cannot be occluded with the balloon
catheter (arrow) because of a very large gastrorenal shunt with rapid blood flow.
FIGURE 29-7. A 72-year-old man with grade 1 gastric varices. Retrograde venography
under balloon occlusion of gastrorenal shunt shows well-opacified gastric varices without
evidence of collateral veins.
FIGURE 29-8. A 70-year-old man with grade 3 gastric varices. A: Retrograde venography
under balloon occlusion of the gastrorenal shunt shows the inferior phrenic vein (solid
arrow), but gastric varices are only partially visible (open arrow). B: A 2.9-Fr microcatheter
was advanced via a 6-Fr balloon catheter into the inferior phrenic vein and then it was
embolized with microcoils. C: Retrograde venography shows gastric varices clearly after
occlusion of the inferior phrenic vein with coils (arrow), then 25 mL of EO was infused to
occlude the varices.
Complications
Hematuria frequently appears, but it rarely leads to renal failure when haptoglobin is
concomitantly used. Pulmonary edema and shock due to the use of EOI have been infrequently
reported (15).
Some facilities set the maximum dose of EOI at 0.4 mL/kg. EO should be used carefully
because pulmonary edema (16), hemothorax (17), disseminated intravascular coagulation (18),
and cardiogenic shock are caused by EO in rare cases. The volume of EO can be reduced if it
is injected after injection of 50% dextrose in water (D50W). Allergic reactions to ethanol may
occur.
Pain may occur immediately after ethanol injection. Although ethanol (ethyl alcohol) can be a
strong sclerosing material in the vessels, rapid injection causes acute alcohol poisoning. Bolus
injection of ~15 g of absolute ethanol raises the blood alcohol level to 300 to 400 mg/100 mL,
increasing the risk of coma. Care should be exercised to avoid excessive administration, >15 g,
of ethanol, and patients must be carefully observed.
Coil migration after embolization of the inferior phrenic vein has been infrequently reported to
occur due to the change
in the direction of blood flow. It is essential to use a reasonably large coil.
FIGURE 29-9. A 65-year-old man with gastric varices and a ring-type GR shunt. A:
Venography under balloon occlusion of the gastrorenal shunt shows a second vein
connecting to the left renal vein, and gastric varices are not shown. This is known as a
ring-type gastrorenal shunt. B: In cases with a ring-type gastrorenal shunt, the balloon is
inflated at the confluence point of the two veins. Gastric varices are clearly depicted.
Portal thrombosis can be caused by inflow of the sclerosant from the left gastric vein into the
portal vein or from the splenorenal shunt into the splenic vein. In some cases, a splenorenal
shunt joins the adrenal vein separately from the GR shunt. There is a possibility that EO from
the balloon catheter may flow into the splenic vein to produce thrombus in the portal vein. The
blood flow should be checked thoroughly and carefully.
CONCLUSIONS AND FUTURE PROSPECTS

B-RTO is used to embolize varices from downstream, in contrast to percutaneous transhepatic
obliteration, which embolizes varices from upstream. B-RTO can be employed not only for
gastric varices but also for duodenal varices (19,20). In many cases, the portal blood flow
becomes hepatopetal again, and half of the patients who underwent B-RTO showed a
secondary effect of improvement in liver function, revealing that B-RTO has a therapeutic effect
on liver cirrhosis. Further development of B-RTO is fully expected.
References
1. Grant WC, Jhaveri RR, McHutchinson, et al. Trends in health care resources use for
Hepatitis C Virus infection in the United States. Hepatology. 2005;42:1406-1413.
2. Lunderquist A, Borjesson B, Owman T, et al. Isobutyl-2-cyanoacrylate (bucrylate) in

obliteration of gastric coronary vein and esophageal varices. AJR. 1978;130:1-6.
3. Nakao N, Sugiki K, Chin K, et al. Transhepatic embolization of gastroesophageal varices

in liver cirrhosis. Nippon Igaku Hoshasen Gakkai Zasshi. 1978;38:852-861.
4. Spigos DG, Tan WS, Mozes MF, et al. Partial splenic embolization in the treatment of
hypersplenism. AJR. 1979;132:777-782.
5. Rosch J, Hanafee WN, Snow H. Transjugular portal venography and radiologic portocaval
shunt; an experimental study. Radiology. 1969;92:1112-1114.
6. Kanagawa H, Mima S, Kouyama H, et al. Treatment of gastric fundal varices by balloon-

occluded retrograde transvenous obliteration. J Gastroenterol Hepatol. 1996;11:51-58.
7. Hirota S, Matsumoto S, Tomita M et al. Retrograde transvenous obliteration of gastric

varices. Radiology. 1999;211:349-356.
8. Fukuda T, Hirota S, Sugimura K. Long-term results of balloon-occluded retrograde

transvenous obliteration for the treatment of gastric varices and hepatic encephalopathy. J
9. Hirota S, Ichikawa S, Matsumoto S, et al. Interventional radiologic treatment for

idiopathic portal hypertension. Cardiovasc Intervent Radiol. 1999;22:311-314.
10. Fukuda T, Hirota S, Sugimoto K, et al. Downgrading of gastric varices with multiple
collateral veins in balloon-occluded retrograde transvenous obliteration. J Vasc Interv
Radiol. 2005;16(10):1379-1383.
11. Fukuda T, Hirota S, Matsumoto S, et al. Application of balloon-occluded retrograde

transvenous obliteration to gastric varices complicating refractory ascites. Cardiovasc
Intervent Radiol. 2004;27: 64-67.
12. Hirota S, Kobayshi K, Maeda H, et al. Balloon-occluded retrograde transvenous

obliteration for portal hypertension. Radiat Med. 2006;24(4):315-320.
13. Masaki M, Obara K, Suzuki S, et al. The destructive effects of sclerosant ethanolamine
oleate on mammalian vessel endothelium. Gastroenterol Jpn. 1990;25:230-235.
14. Miyoshi H, Oshiba S, Matsumoto A, et al. Haptoglobin prevents renal dysfunction

associated with intravariceal infusion of ethanolamine oleate. Am J Gastroenterol.
1991;86:1638-1641.
15. Lee JY, Moon SH, Lee SM, et al. A case of noncardiogenic pulmonary edema by
ethanolamine oleate. Korean J Intern Med. 1994;9:125-127.
16. Uchibori S. Pulmonary circulatory disturbance following endoscopic injection

sclerotherapy. Nippon Kyobu Shikkan Gakkai Zasshi. 1993;31:833-839.
17. Rajagopalan N, Hoffstein V. Hemothorax following uncomplicated sclerotherapy for

esophageal varices. Chest. 1994;106:314-315.
18. Bellary SV, Isaacs P. Disseminated intravascular coagulation (DIC) after endoscopic
injection sclerotherapy with ethanolamine oleate [letter]. Endoscopy. 1990;22:151.
19. Tsurusaki M, Sugimoto K, Matsumoto S, et al. Bleeding duodenal varices successfully

treated with balloon-occluded retrograde transvenous obliteration (B-RTO) assisted by CT
during arterial portography. Cardiovasc Interv Radiol. 2006;29(6):1148-1151.
20. Zamora CA, Sugimoto K, Tsurusaki M, et al. Endovascular obliteration of bleeding

duodenal varices in patients with liver cirrhosis. Eur Radiol. 2006; 16(1):73-79.
Endovascular Management in Liver Transplantation
Chapter 30
Endovascular Management in Liver Transplantation
Kyu Bo Sung
Gi-young Ko
Liver transplantation (LT) was developed for the treatment of hepatic failure, and the first
human LT was done in 1963 (1). From the 1990s, LT was generally accepted as a treatment
modality for both end-stage liver disease and selected liver malignancies. Initially, LT was
started with deceased-donor whole-size LT (whole-size LT) as in other organ transplantation,
but there is now a shortage of deceased liver donors. As a solution, deceased-donor split LT
(split LT) began in 1989 (2), and living-donor LT (LDLT) in the early 1990s (3, 4, 5, 6, 7).
Current liver transplantation techniques include whole-size LT, reduced-size LT, split LT, and
single or dual LDLT. Two donors give a part of their liver to one adult recipient simultaneously in
dual LDLT (8,9). LDLT began in Asia and is gaining acceptance in the United States and Europe
(10,11). Whole-size LT is a less complex surgical procedure than other transplantation
techniques because anastomoses involve large structures. Reduced-size LT, split LT, and LDLT
are more complicated surgical procedures due to the need for multiple anastomoses of smaller
ductal structures, and dual LDLT is more than twice as complicated compared to single LDLT.
These small-size vascular and bile duct anastomoses have resulted in a higher incidence of
stenosis, and interventional management is essential for a successful outcome of reduced-size
LT, split LT, and LDLT.
The role of interventional radiology has evolved with improvements in LT techniques. In our
experience, surgeons encountered many problems when they began LT and also during their
learning curve in each successive development in transplantation technique. Interventional
radiology had a crucial role in dealing with early problems with each technique. Currently the
most useful interventional procedures are percutaneous transhepatic biliary drainage and
stricture dilatation, which, if performed promptly, can significantly improve quality of life by
preventing repeated septic attacks and deterioration of the liver function. This is particularly true
in LDLT. More than 1,200 cases of LT have been performed at our institution, Asan Medical
Center (AMC; Seoul, Korea), since 1992, and >200 cases per year in 2004 and 2005. AMC
has developed several new LT techniques, such as the modified right lobe LDLT and dual LDLT.
More than 90% of LTs are adult-to-adult LDLT, and one quarter of these are dual LDLT. We
retrospectively analyzed 613 patients (59.1%) who needed interventional procedures before,
during, and after LT among 1,037 LDLT patients. The most common interventional procedure
was percutaneous drainage of fluid collection (34.5%), followed by percutaneous transhepatic
biliary drainage for bile leak and biliary stricture dilatation (23.9%). The most common vascular
interventional procedure was embolization for hemorrhage (14.2%). Balloon dilatation and
stenting for vascular stenosis or kinking were also performed at various sites including the
hepatic vein (9.7%), portal vein (6.4%), hepatic artery (1.2%), and inferior vena cava (IVC;
1.2%) (Table 30-1).
The success rate of LT at AMC is 95%. Complications of LT are currently assessed first by
interventional radiologists, and most cases are managed by interventional radiology. This
chapter includes our experiences, both reported and unreported, with interventional treatments
in LT and reviews relevant literature.
IMAGING BEFORE LIVER TRANSPLANTATION

Computed tomography (CT), including CT angiography, is the mainstay for evaluating recipients
and donors. For recipients, CT evaluates the size and presence of thrombus in the portal vein,
varices requiring ligation during operation, the size and suitability of the hepatic artery, intra-
and extrahepatic extension of malignancy or tumor thrombus within the portal vein, and
aneurysms of the splenic artery. Also, detection of a right pleural effusion and prompt
percutaneous drainage can improve lung function and the outcome of LT. This is because large
right pleural effusions can bulge into the abdominal cavity during LT, limiting access and
visualization and leaving inadequate space for the transplanted liver.
For living donors, CT with CT angiography evaluates the graft volume and size and any
anatomical variations of hepatic artery and veins. In addition, bile duct variants can be
evaluated with magnetic resonance (MR) cholangiography. Using these imaging modalities, we
can select suitable donors who require more simple surgical techniques and thereby increase
the success rate of LDLT. When the graft volume from a single donor is not enough for the
recipient, a dual LDLT can be considered. For deceased donors imaging can also be helpful.
ANASTOMOSIS OF HEPATIC ARTERY, VEINS, AND BILE DUCT

Whole-Size Liver Transplantation
Although vascular reconstructions in whole-size LT are usually end-to-end anastomosis of the
suprahepatic IVC, infrahepatic IVC, hepatic artery, and main portal vein, there are many
alternative techniques in vascular reconstruction. A piggyback technique is an alternative
method for reconstruction of the IVC. The hepatic vein is surgically conjoined to create a single
lumen that is anastomosed to the suprahepatic IVC. Graft interposition can be used for portal
vein reconstruction. Various hepatic arterial reconstructions are used, depending on the
suitability of the artery and variations of the anatomy. Hepatic arterial reconstruction can be
created at various locations including the common hepatic artery, proper hepatic artery, and a
branch of the celiac trunk or aorta. Multiple anastomoses of the hepatic artery are employed
for anatomic variations. Jump grafts from the aorta to the hepatic artery can be placed when
there is an inadequate hepatic artery. Bile duct anastomosis is done with duct-to-duct
anastomosis or a choledochojejunostomy at the common bile duct level.
TABLE 30-1 INTERVENTIONAL PROCEDURES IN 613 OF 1,037 LDLTs
PERFORMED AT AMC
No. of patients Incidence
Drainage of fluid collectiona 358 34.5%
PTBD for bile leak or biliary stricture 248 23.9%
Embolization for bleeding control 147 14.2%
For increase hepatic vein outflow 101 9.7%
Balloon angioplasty 13
Stent 88
For increased portal vein inflow 66 6.4%
Intraoperative stent 36
Percutaneous stent 26
For management of IVC stenosis and kinking 12 1.2%
For increased hepatic arterial flow 12 1.2%
Stent 4
a Mainly drainage of pleural effusion.

FIGURE 30-1. Scheme for modified right lobe graft in LDLT. A: Ligation of the tributaries
(V5, V8) of the middle hepatic vein (MHV) originating from the anterior segment of the right
lobe graft can induce congestion of the anterior segment. B: In the modified right lobe
graft, V5 and V8 are reconstructed to the recipient's middle and/or left hepatic vein
(M/LHV) with vein graft interposition to prevent congestion of the anterior segment.
Reduced-Size Liver Transplantation, Split Liver

Transplantation, and Living-Donor Liver Transplantation
Partial liver grafts are transplanted with following surgical techniques. Hepatic vein
reconstruction is simple in left lobe transplantation. On the other hand, for right lobe
transplantation all hepatic veins >5 mm in diameter are reconstructed to prevent hepatic
congestion (12,13). Only the right hepatic vein is reconstructed in some patients, whereas more
than two hepatic veins are reconstructed in others including the right hepatic vein, accessory
right hepatic vein, inferior hepatic vein, and middle hepatic vein tributaries from segments 5 (V5)
and 8 (V8). The right hepatic vein, accessory right hepatic vein and inferior hepatic veins are
usually anastomosed directly to the right hepatic vein or IVC, but a graft is interposed in
reconstruction of V5 and V8 tributaries from the cut surface to the recipient's middle and/or left
hepatic vein (Fig. 30-1) (14,15). The reconstructed V5 and V8 can be patent for a long period.
If not, the venous outflow of segments 5 and 8 can drain into the other patent hepatic veins by
development of intrahepatic collaterals.
Single-portal vein anastomosis is performed for patients with normal anatomy, whereas two
anastomotic connections are considered in patients with portal vein variations such as a
posterior segment branch from the main portal vein. However, a bench procedure using a Y
graft acquired from the recipient's portal bifurcation can facilitate the portal vein anastomosis.
Graft interposition can be performed in portal vein reconstruction for patients with an unsuitable
portal vein.
Hepatic arteries are the smallest structure for reconstruction in LT. Multiple hepatic arteries (as
a normal variation) or hepatic arterial injury caused by repeated transarterial
chemoembolization are reasons for difficult hepatic arterial anastomoses. An end-to-end
anastomosis is created between the hepatic arteries using a microscope, but the reconstruction
may also be done with the right gastroepiploic artery. One of the hepatic arteries can be ligated
if well-developed intrahepatic arterial collaterals are present.
The bile duct is connected with duct-to-duct anastomosis or hepaticojejunostomy at the level of
the right and left duct branch or common hepatic duct. Normal bile duct anatomy, the common
hepatic duct bifurcating into the left and right hepatic ducts (right hepatic duct subsequently
bifurcating into the anterior and posterior segmental ducts), is seen in only 52% of patients
(16). Multiple anastomoses are essential with bile duct variations. Bile duct stenoses after
LDLT occur not only at the anastomosis, but also from ischemic injury of the bile duct
presenting as combined multiple intrahepatic duct strictures. Bile duct stricturing is the Achilles'
heel of LDLT and cannot currently be overcome with surgical management alone. The proper
treatment of bile duct strictures is not surgical, and it is usually either interventional or
endoscopic treatment. Because of multiple anastomoses and combined multiple intrahepatic
duct strictures, interventional management through one or more percutaneous transhepatic
biliary drainage is the only way to treat most patients.
Dual LDLT can be done with a combination of various types of grafts such as combinations of
lobes (two left lobes or a left and right lobe), combinations of a lobe and a segment (right lobe
and lateral segment or posterior segment and left lobe), or combinations of segments (lateral
segment or extended lateral segment and lateral segment or extended lateral segment) (17).
VASCULAR INTERVENTIONS BEFORE LIVER

TRANSPLANTATION
Transjugular intrahepatic portosystemic shunt (TIPS) has been used for the prevention of
variceal bleeding while waiting for a donor, but currently TIPS is not recommended before
transplantation.
Splenic Artery Aneurysm Embolization

The incidence of splenic artery aneurysm (SAA) in patients with liver cirrhosis ranges from 7%
to 17% (18), and SAA rupture after LT has resulted in a significantly higher morbidity and
mortality according to recent literature (19,20). Classically, the management has been surgical,
with ligation or resection of the aneurysmal arterial segment with or without splenectomy.
However, preservation of the spleen is important due to the immunologic function of the spleen
(19,21). Therefore, even asymptomatic SAA or small-sized SAA should be embolized prior to
LT to prevent growth and rupture of the SAA (22,23). Coil embolization is usually performed
from the distal to the proximal portion of the aneurysm. There may also be a role for covered
stents for isolating shorter fusiform aneurysms.
VASCULAR INTERVENTIONS DURING LIVER

TRANSPLANTATION
Intraoperative Portal Venogram
Adequate flow through the portal vein is essential for hypertrophy of the graft after
transplantation. Interruption of large portosystemic collaterals, such as a coronary vein or
splenorenal shunt, is performed during operation to promote increased hepatopetal flow in the
portal vein. A portal venogram is helpful for evaluation of the direction of flow before and after
the ligation of varices. A catheter is inserted through the inferior mesenteric vein or the
tributaries of the superior mesenteric vein for contrast injection, and the study is acquired while
the anesthesiologist suspends respiration. The inferior mesenteric vein is ligated after removal
of the catheter. Variceal embolization through this route is possible but is more time-consuming
and less effective than surgical ligation.
Portal Vein Stenting

Stenting of the portal vein is usually done for prevention of vascular kinking and for dilatation of
a small-sized portal vein with or without partial thrombosis. A self-expandable stent is
recommended because balloon dilatation immediately after portal vein anastomosis may not be
safe. Good flexibility and conformability are important stent properties for preventing
straightening of the curved portal vein because otherwise stenting alone can cause abrupt
kinking with an acute angle at the distal end. This can result in a stenosis or obstruction of the
portal vein. The route of stent placement is through the inferior mesenteric vein or tributary of
the superior mesenteric vein. A 10-mm-diameter stent is usually enough to maintain portal flow,
but size should be matched to the portal vein. The length of the required stent is measured with
a guide wire as the distance from the intrahepatic portal bifurcation to the junction of the main
portal vein and superior mesenteric vein. A 60-mm-long stent is usually used (ranging from 40
to 80 mm). Balloon dilatation may be needed if the waist of the stent is not at the anastomotic
site of the portal vein; otherwise it suffices to wait for spontaneous expansion. Stent insertion in
the left lobe graft is difficult because of the anteroposterior direction of the umbilical portion of
the left portal vein. The most distal branch from the umbilical portion (segment 3 branch) must
be checked on the donor CT. The guide wire is inserted into the segment 3 branch, and the
stent deployed across the proximal branches. If the guide wire is placed in the segment 2
branch, which is more proximal, the stent may not adequately cover the anastomotic site of the
portal vein.
Intraoperative stent placement of a small-sized or thrombosed portal vein on CT must be
planned prior to operation. Intraoperative stent placement should be considered part of the LT
since it can shorten the operation time and can provide better patency then a jump graft. Even
in the absence of the portal vein on CT due to decreased size or thrombosis, end-to-end
anastomosis after thrombectomy followed by stent placement is possible without jump graft
(Fig. 30-2). At AMC, self-expandable stents were inserted during operations in 36 patients for
small-sized, thrombosed, or kinked portal veins. Stent placement was successful in all patients.
Stent occlusion developed in two patients (5.3%) during an 18-month (range, 0.3- to 73.3-
month) follow-up period.
FIGURE 30-2. A 44-year-old man with main portal vein obliteration, probably due to
chronic thrombosis. A, B: Preoperative enhanced axial CT and coronal multiplanar
reconstruction image show an obliterated main portal vein with well-developed perisplenic
collateral veins. C: Direct superior mesenteric venography through inferior mesenteric vein
cannulation (white arrow) following portal vein anastomosis and thrombectomy shows
stenosis due to residual thrombus (black arrow). D: Direct portal venography after 10-mm-
diameter stent placement following balloon dilatation shows markedly improved portal flow.
E: Coronal multiplanar reconstruction CT obtained 13 days after transplantation shows the
patent stent.
VASCULAR INTERVENTIONS AFTER TRANSPLANTATION

Imaging Evaluation
CT with CT angiography, Doppler ultrasound, and radioisotope biliary scan are the commonly
used imaging modalities in the evaluation of graft liver function. Evaluation of any unusual clinical
manifestation must be done promptly with CT. Either suspected abnormal findings of vascular
structure on CT or clinical manifestations suggestive of vascular abnormality without positive
findings on CT are again examined by Doppler ultrasound. Some abnormal findings on CT alone
are enough to justify performing interventional procedures such as abnormal fluid collection,
intrahepatic arterial aneurysm, active bleeding, and total thrombosis of the portal vein.
However, stenosis of vascular structures on CT and Doppler ultrasound is often not enough for
a definite diagnosis. These findings must be matched with the clinical manifestations and
laboratory findings, and the decision for any treatment must be made by the transplantation
surgeon. In addition, imaging is helpful to evaluate whether splenic artery banding or ligation for
the prevention of splenic artery steal syndrome and variceal/left renal vein ligation to increase
the hepatopetal flow of the portal vein were effectively done.
Hepatic Artery Stenosis and Thrombosis

Sufficient hepatic arterial flow is essential for graft survival after LT. Stenoses usually occur at
arterial anastomotic sites. Decreased or absent arterial flow can induce graft failure or cause
nonanastomotic biliary strictures. Stenosis or occlusion of the hepatic artery is mainly due to
poor surgical technique or poor arterial status, and the reported incidence of hepatic arterial
stenosis or occlusion is 12% (24,25). Selective arteriography of the celiac trunk or hepatic
artery can be dangerous due to risk of dissection. Therefore, patency of the hepatic artery
must be evaluated with noninvasive imaging modalities, and hepatic arteriography is considered
only in cases when interventional treatment is definitely indicated.
Not all arterial stenoses seen on CT or Doppler ultrasonography require treatment, especially in
many cases of a mild degree of stenosis with normal liver function. However, symptomatic
arterial stenoses do require treatment. Surgical exploration and reconstruction are a good
option. Percutaneous transluminal balloon dilatation (PTA) and stent placement are alternative
interventional techniques for arterial stenosis.
Publications on balloon angioplasty report safety and improved liver function, but also
recurrence of stenoses requiring repeated PTA (26, 27, 28, 29, 30, 31, 32, 33, 34). However,
the majority of these papers have only a limited number of the patients, without long term
follow-up; moreover, retransplantations were done in some of these cases.
There are several reports on stent placement following failed angioplasty or restenosis (29,32,
33, 34, 35). Unfortunately, these are case reports or have a limited number of cases. Coronary
stents may also be suitable for hepatic arterial stenosis. Balloon-expandable and self-
expandable stents have been used. However, it is important to keep in mind that once a stent is
deployed in the hepatic artery, it will make anastomosis of the hepatic artery during
retransplantation extremely difficult.
Hepatic arterial thromboses occur with or without arterial stenosis, and the reported incidence
is 2% to 8% in adult LT (36, 37, 38, 39, 40, 41). Hepatic arterial thrombosis within several
weeks has a high risk of graft failure, yet it can be asymptomatic. The therapeutic options for
hepatic arterial thrombosis include urgent retransplantation and observation. Salvage of the
graft with surgical revision and thrombectomy is reported in 20% to 40% of patients (40,42).
Another group reported survival rates of surgical thrombectomy of 82% in asymptomatic
patients and 40% in symptomatic patients (43).
Fibrinolytic therapy and pharmacomechanical thrombectomy coupled with PTA and stent
placement are other feasible therapeutic options. Several case reports are available on
interventional treatment of arterial thrombosis (44, 45, 46). However, thrombolytic therapy can
induce bleeding in patients with recent major abdominal surgery, especially during the early
postoperative period.
We deployed a hepatic arterial stent in a case with arterial stenosis at the anastomotic site
combined with partial thrombosis in the proximal portion (Fig. 30-3). Stent placement for
restenosis following PTA was also successful, and coil embolization of a growing
pseudoaneurysm through the mesh of the stent was performed (Fig. 30-4). Patency of the
stent was observed during 25 and 58 months of follow-up.
Hepatic Artery Pseudoaneurysm

Extrahepatic pseudoaneurysm is a rare complication and is usually encountered at the
anastomotic site of the hepatic artery. However, depending on the surgical reconstruction
technique of the hepatic artery during transplantation, the anastomotic site of the hepatic artery
can mimic an aneurysm. Therefore, it is important to check what type of artery reconstruction
technique was performed prior to the diagnosis of pseudoaneurysm. Pseudoaneurysms are
also seen at the stump of an arterial branch or other portions of the hepatic artery (47).
Pseudoaneurysms usually grow due to high arterial pressure and may result in rupture causing
massive bleeding. Therefore, the detection and treatment of pseudoaneurysms before rupture
are critical, especially in cases with rapid growth on short-term follow-up CT. Surgical
exploration and repair are usually required, but embolization is an alternative therapeutic option.
Surgical ligation and hepatic artery embolization have been reported in seven patients, done 10
to 70 days following transplantation, with three subsequent deaths (48). Successful stent-graft
placements have been reported in a limited number of cases using coronary stent-grafts
(49,50).
The causes of intrahepatic pseudoaneurysms are iatrogenic such as liver biopsy, percutaneous
transhepatic biliary drainage, and transhepatic aspiration of peritoneal or intrahepatic fluid.
Intrahepatic pseudoaneurysms can also develop from trauma to a graft from a living donor
during surgery or from undetected liver trauma of a deceased donor. The detection of a
pseudoaneurysm before rupture can be done with CT while the ruptured pseudoaneurysm can
be detected from symptoms including hemobilia, hemoperitoneum, or subcapsular hematoma.
All intrahepatic pseudoaneurysms must be treated because of the possibility of rupture. Coil
embolization from the distal to the proximal portion of the pseudoaneurysm is the best method
because it can preserve the distal hepatic artery through intrahepatic collaterals. No significant
deterioration of liver function after selective embolization of pseudoaneurysms has been
observed.
A subcapsular rupture of an intrahepatic pseudoaneurysm is treated in a different manner. The
bleeding comes from the ruptured aneurysm and parenchyma surface due to separation injury
from the capsule. This hematoma compresses the liver
parenchyma, compromising portal inflow and hepatic venous outflow. Surgical evacuation of
such acute hematomas will only cause massive rebleeding because of the sudden loss of the
compression effect of the hematoma. Moreover, surgical intervention cannot solve the massive
bleeding from the ruptured pseudoaneurysm. Pseudoaneurysms, arterioportal fistulae, and
multiple small foci of extravasation from the surface are seen on arteriography. The ruptured
aneurysm should be treated with coil embolization while a pigtail catheter should be inserted at
the same time into the subcapsular hematoma to decompress it slowly and to improve portal
perfusion and hepatic venous outflow (Fig. 30-5). Continuous transfusion must be followed with
continuous monitoring of the hemoglobin level. Peripheral embolization of multiple surface
bleeding is controversial due to the possible deterioration of liver function. We did peripheral
embolization with gelatin sponge cubes in two patients, whereas no embolization was done in
one patient. All three patients survived.
FIGURE 30-3. A 54-year-old woman with hepatic artery stenosis at the anastomotic site
combined with partial thrombosis. A: Celiac arteriogram shows stenosis at the anastomotic
site of the hepatic artery (white arrow) and intraluminal filling defect due to partial thrombus
(black arrow). B: Celiac arteriogram obtained after stent placement (4 mm in diameter and
32 mm long) shows the normalized and patent lumen of the hepatic artery at the stenosis
(arrow). C: Coronal reconstruction CT image obtained 7 months after stent placement
shows the patent stent (arrow).
Despite reports of successful embolization of pseudoaneurysms with percutaneous thrombin

injection (51,52), we lost two patients after percutaneous thrombin injection. Extensive
thrombosis developed in the intrahepatic artery in one patient, but the cause was uncertain in
the other patient.
Hepatic Vein Stenosis and Kinking

Stenosis or kinking of the hepatic vein is only a complication after reduced-size LT, split LT, and
LDLT because an end-to-end or end-to-side anastomosis to the IVC is done for hepatic vein
reconstruction in whole-size LT. The hepatic veins are evaluated with CT and Doppler
ultrasound, but clinical manifestations and laboratory findings should also be simultaneously
considered. Decreased hepatic venous outflow due to stenosis or obstruction typically presents
as an inhomogeneous area of the graft on delayed-phase CT. A low-density area of the graft
can
be correlated with the location of a severe hepatic vein stenosis or obstruction in typical cases.
The reconstructed V5 or V8 may not be opacified even in delayed-phase CT, but this finding
does not always indicate the presence of thrombosis. It might possibly represent markedly
delayed filling without thrombosis. Direct measurement of the pressure gradient with hepatic
venogram can be used in suspicious cases. A pressure gradient >10 mm Hg across the
anastomotic site and contrast stasis in the hepatic vein suggests a significant stenosis. The
decision whether to treat this stenosis of the hepatic vein is an entirely different matter.
Stenosis of a single hepatic vein reconstruction is a good indication for treatment. On the other
hand, all stenoses or obstructions of small hepatic veins do not require treatment when multiple
hepatic vein reconstructions are done with an adequate graft volume. However, treatment
should not be delayed when required because of potential progression to thrombophlebitis and
graft loss (Fig. 30-6). Prophylactic hepatic vein stenting just after transplantation, if the surgeon
has technical concerns during the transplantation, might be a feasible method for graft saving.
FIGURE 30-4. A 47-year-old man with stenosis and pseudoaneurysm in the hepatic artery.
A: Common hepatic arteriogram obtained 48 days after liver transplantation shows a
stenosis (black arrow) and a pseudoaneurysm (white arrow) in the proper hepatic artery.
B, C: The stenosis was treated with stent placement (C) following balloon angioplasty (B).
The stenosis disappeared after stent placement, but the pseudoaneurysm (white arrow)
was persistent. D: Final arteriogram taken following coil embolization of the
pseudoaneurysm shows the patent intrahepatic arterial flow and disappearance of the
pseudoaneurysm.
Primary stent placement with a self-expandable stent is generally used in the acute stage
without balloon dilatation to avoid the possibility of rupture of the hepatic vein. Another reason
for primary stent placement is reduced flow due to vascular kinking rather than stenosis in the
acute stage. Stenting of an interposed graft immediately after reconstruction of V5 and V8 is
also feasible and safe. Balloon dilatation is usually reserved for the chronic stage of a
suspicious stenosis in adult patients or pediatric patients for whom a stent may limit the lumen
with patient growth. The size of the stent is decided with measurement on CT and hepatic
venography, but the size of the vessel may be enlarged due to obstruction. Self-expandable
stents with good flexibility and reasonable radial force are the best choice. Irritation from the
end of the stent can induce the hepatic vein stenosis. Stents for the right hepatic vein are
usually 10 mm in diameter, while stents 6 to 8 mm in diameter are used for inferior and
interposed graft of V5 and V8. Usually, the right internal jugular vein is punctured for the
procedure, but if the direction of the vein is upward on imaging, then puncture of the right
femoral vein may be a better choice. In addition, a percutaneous puncture of the hepatic vein
can be an alternative route for selection of the hepatic vein, especially when the approach
through the IVC is difficult. In selecting the hepatic vein from the IVC, the right inferior phrenic
vein can be mistaken as the hepatic vein, but the former can be differentiated by the typical
shape of the latter.
FIGURE 30-5. A 54-year-old man with a massive subcapsular hematoma. A: Enhanced CT
obtained 11 days after percutaneous stent placement in the portal vein shows an
intrahepatic pseudoaneurysm (arrow). B: Five-day follow-up CT shows the ruptured
pseudoaneurysm with parenchymal (arrow) and subcapsular hematoma (star). C: Follow-
up CT obtained after completion of two sessions of transarterial intrahepatic arterial
embolization of the pseudoaneurysm with coils shows the increased extent of the
subcapsular hematoma (star). D: Repeat common hepatic arteriogram after the previous
coil embolization of the pseudoaneurysm (white arrow) shows numerous suspicious foci of
arterial bleeding (arrowheads) along the detached liver parenchyma from the liver capsule.
E: Common hepatic arteriogram obtained after peripheral intrahepatic arterial embolization
using gelatin sponge shows disappearance of the bleeding foci. A drainage catheter was
placed in the subcapsular hematoma. F: Follow-up CT about 5.5 months after embolization
and hematoma drainage shows the normalized liver.
FIGURE 30-6. A 41-year-old man with occlusion at the anastomotic site of the hepatic vein
in the right graft following dual LDLT with two left lobes. A: Enhanced CT obtained 3
months after dual LDLT shows mild inhomogeneous attenuation in the right graft. B:
Enhanced CT obtained 3.5 months after the dual LDLT shows a markedly decreased liver
density and volume in the right graft. C: Direct hepatic venogram obtained 26 days after
3.5-month follow-up CT (B) shows the thrombotic occlusion of the hepatic vein in the right
graft. D: Hepatic venous outflow is restored after stent placement (arrows) across the
hepatic venous anastomosis. E: However, follow-up CT revealed the continuous atrophy of
the right graft.
The flow pattern of the hepatic vein on Doppler ultrasound changes immediately when
successful stenting is done, and the typical low-density area of the liver on CT usually
disappears within a week with improvement of clinical manifestations and laboratory findings
(Fig. 30-7). Good patency of isolated stenosed hepatic veins following balloon angioplasty has
been reported in a limited number of patients with a short follow-up period (53). Our early
reported data described stent placement in 22 patients and PTA in 5 patients, and clinical
success was achieved in 20 patients (73%) with a follow-up period of 3 to 214 weeks (mean,
49 weeks) (54).
Our more recent data include stent placement performed in 84 venous anastomoses from 60
patients and technical success was achieved in 81 anastomoses (96.4%). Clinical improvement
was achieved in 49 patients (81.7%) after stent placement for a mean follow-up period of 25.1
months. Clinical recurrence of hepatic vein obstruction occurred in three patients (6.1%) who
had restenoses just peripheral to the previously inserted stents. The overall 1-, 2-, and 3-year
cumulative primary patency rates of 81 stents inserted in the hepatic veins were 88.2%, 85.9%,
and 77.6%, respectively. Sometimes up to five stents were placed at several venous
anastomoses with stenoses (Fig. 30-8).
Inferior Vena Cava Stenosis and Kinking

Stenosis and kinking of the IVC are a problem with full-size LT. The reported incidence is 1%
(55), and the clinical manifestations depend on the location of the stenosis. The clinical
manifestations are similar to those of typical Budd-Chiari syndrome, with ascites and hepatic
dysfunction in stenosis or obstruction of the suprahepatic IVC and lower extremity edema with
stenosis or obstruction of the infrahepatic IVC (56,57).
The diagnosis of IVC stenosis is established by Doppler ultrasound and/or CT with CT
angiography in addition to the typical clinical manifestations. Definitive diagnosis is made by
direct vena cavogram with pressure measurements during the interventional procedure. PTA
and stent placement have been reported to be the treatment of choice for stenosis (28,58, 59,
60) and kinking of the IVC. Again, these reports include a limited number of patients due to the
low incidence of postoperative stenosis of the IVC. The restenosis rate is somewhat higher in
cases with simple balloon dilatation alone than in cases with stent placement. Self-expandable
stents are preferred for caval stenosis. The appropriate stent size should be decided on, and a
longer stent is better suited for the prevention of migration. However, extending the stent into
the right atrium may induce arrhythmia. There is also a report on successful catheter-directed
thrombolysis followed by stent placement for a completely thrombosed IVC (61).
Interestingly, kinking at the anastomotic site of the IVC can induce a sudden decrease in central
venous pressure when lack of IVC flow occurs during the operation. Intraoperative stent
insertion through the femoral vein is a better and simpler treatment than surgical reanastomosis
to preserve the flow of the IVC.
IVC stenosis is not a problem after LDLT and split LT because end-to-end vascular
reconstructions are performed for the recipient's hepatic vein while end-to-side vascular
reconstructions are done for the recipient's IVC. Diffuse narrowing of the hepatic segment of
the IVC is seen on CT in these patients without symptoms. This is due to dissection of the IVC
during explantation of the recipient liver.
Portal Vein Stenosis and Thrombosis

These complications can be caused by poor surgical technique for anastomosis, torsion,
tension, or venous redundancy induced by the geometric relationship of the graft to the
recipient's portal vein. Impairment of portal flow induces worsening of liver function, poor
hypertrophy or atrophy of the graft, and, finally, graft failure (Fig. 30-9). The incidence of portal
vein thrombosis is 1% to 3% (62).
The diagnosis of portal vein thrombosis is easily made by CT and Doppler ultrasound. On the
other hand, portal vein stenosis is not straightforward on imaging, and the clinical
manifestations should be taken into consideration before making the diagnosis. Some degree of
difference in flow velocity and stenosis at the anastomosis site are not uncommon findings and
are not clinically significant (63,64). Periodic follow-up is important for the evaluation of a
suspected portal vein stenosis. Completely thrombosed portal veins need immediate treatment,
but partial thrombosis may resolve by preserving the surrounding flow. Partial thrombosis with
preserved flow can be observed without any treatment during the immediate postoperative
period, and anticoagulation is helpful for chronic cases.
Treatment options include surgery such as surgical revision with or without thrombectomy,
venous bypass and retransplantation, and radiologic interventions. Successful balloon dilatation
with or without stent placement has been reported in portal vein stenosis using the
percutaneous transhepatic route or transjugular-transhepatic route (58,65,66). Technical
success was reported in 19 of 25 pediatric patients, with venous patency for 5 to 61 months
(mean, 46 months) (67), but there are no data in adult LT.
Percutaneous transhepatic regional thrombolysis or mechanical thrombectomy followed by
balloon dilatation and stent placement are the interventional alternatives for portal vein stenosis
combined with portal vein thrombosis. Some reports on this technique are available (68,69), but
there is a risk of graft injury from percutaneous portal puncture and bleeding from thrombolytic
therapy.
Intervention with surgical re-exploration is ideal in the early posttransplant period (70). The
complications of percutaneous transhepatic puncture and thrombolytic therapy can be avoided
with this method. Surgical thrombectomy with portal vein exploration and stent placed through
the inferior mesenteric or a tributary of the superior mesenteric vein can effectively prevent the
occurrence of recurrent thrombosis.
Percutaneous stent placement for portal vein stenosis was tried in 26 patients at AMC, and
technical success was achieved in 24 patients (92.3%). Stent placement with surgical
exploration was attempted in the two failed cases but was unsuccessful, due to inability to
cross the completely occluded segment. Stent occlusion developed in two patients (9.5%)
during the 42.6-month (range, 4.5- to 83.4-month) follow-up period.
FIGURE 30-7. A 42-year-old man with hepatic venous anastomotic stenosis in the right
graft following dual LDLT with two left lobes. A: Enhanced CT obtained 20 days after dual
LDLT shows homogeneous enhancement in both liver grafts with a patent hepatic vein in
the right graft (arrow). B: Follow-up CT obtained 55 days after transplantation, after an
acute deterioration in liver function, shows heterogeneous enhancement in the right graft.
The hepatic vein (arrow) in the right graft is indistinct. C: Direct right hepatic venography
shows a tight stenosis (arrow) at the anastomosis. The pressure gradient across the
stenosis is 12 mmHg. D: Direct hepatic venography after stent placement (arrows) shows
disappearance of the stenosis. The pressure gradient across the stenosis decreased to 1
mm Hg. E: Follow-up CT obtained 16 days after stent placement (arrow) shows the
normalized enhancement of the right graft.
FIGURE 30-8. A 51-year-old woman with five stents placed for treatment of hepatic
venous congestion following single LDLT with right lobe. A: Enhanced CT obtained 2 days
after liver transplantation shows a well-marginated, low-attenuating area (arrowheads) in
the anterior portion of the graft. B-E: Digital plain film shows the five stents placed at the
anastomotic site of the right hepatic vein (black arrowhead), V5 (white arrow), and V8
(black arrow) with interposed graft and two inferior hepatic veins (white arrowheads). F: A
34-day follow-up CT following stent placement across the several hepatic venous
anastomoses shows normalized liver parenchymal enhancement.
FIGURE 30-9. A case of atrophy of one liver graft due to portal vein stenosis following dual
LDLT. Enhanced axial (A) and multiplanar reconstruction oblique axial (B) images obtained
20 days after dual LDLT show a tight stenosis (arrow) of portal vein anastomosis of the
right graft. Follow-up axial CT images obtained 2.5 months (C) and 7.5 months (D) after
dual LDLT show gradual atrophic change of the right graft. Note the thrombosed
intrahepatic portal vein (arrow in C) in the right graft.
Hemorrhage
Bleeding from LT is similar to bleeding from partial resection of the liver except for bleeding
from the arterial anastomotic site. According to our own analysis, bleeding was related to
surgery in 53%, while 40% of bleeding was secondary to a percutaneous procedure. The
remaining 7% of cases were due to spontaneous gastrointestinal bleeding (71).
The diagnosis of bleeding may be made from overt bleeding via surgical drains or decreased
hemoglobin level. CT is the best imaging technique for the evaluation of bleeding. Active
bleeding and increasing size of the hematoma on short-term serial follow-up are positive
findings on CT.
Surgical exploration is indicated in sudden massive bleeding, bleeding with a large amount of
intraperitoneal hematoma, bleeding at a cut surface of the graft, bleeding in the gallbladder
fossa, and bleeding at the hepatic artery anastomosis. The success rate of embolization is low
in cut surface bleeding of the graft and bleeding at the gallbladder fossa, and it is easier to
control the bleeding with surgery (71). Total embolization of the hepatic artery to control
bleeding from the arterial anastomotic site is dangerous in the early posttransplant period.
Other sources of hemorrhage including the right inferior phrenic artery, inferior epigastric artery,
superior epigastric artery, right renal capsular artery, intercostal arteries, and small bowel
bleeding caused by stress ulcers can be controlled by embolization.
FIGURE 30-10. A 57-year-old man with recurrent HCC in the graft. A: Enhanced CT
obtained 117 days after transplantation shows a normal enhancing graft. Follow-up CT
images obtained 129 days (B), 165 days (C), and 188 days (D) after transplantation show
a rapidly growing recurrent tumor.
Transjugular Liver Biopsy
Transjugular liver biopsy is a safe alternative technique to surgical and percutaneous biopsy;
furthermore, it also can be performed in the acute posttransplant period. The advantage of this
technique is that it avoids injury to the liver capsule. On the other hand, complications from
parenchymal and arterial injury can occur in transjugular biopsy. In addition, an injury from the
use of a stiff biopsy instrument at the anastomotic site can also occur. The overall complication
rate is reported to be about 2.4%; death due to intraperitoneal bleeding has been reported,
although these were nontransplantation patients (72).
Transjugular liver biopsy was reported after LT (124 biopsies in 105 patients) without
complications (73). Biopsies were performed within 30 days after whole-size LT, and these
patients had a standard end-to-end caval anastomosis in 89% and piggyback caval-caval
anastomosis in 11%. The technical success rate was 87%, and an adequate specimen was
obtained in 86%.
Transjugular liver biopsy is easy due to the end-to-end anastomosis of hepatic vein in LDLT. We
performed transjugular biopsy with an 18-gauge spring-loaded automated biopsy needle in five
patients with LDLT without complication.
Treatment in Recurrent Hepatocellular Carcinoma

The most common malignant tumor of the liver is hepatocellular carcinoma (HCC), which usually
develops in a cirrhotic
liver. Liver transplantation is limited in HCC by the risk of tumor recurrence. Two sets of criteria
are available for LT of HCC (74,75). These criteria are also used in LDLT. Significant risk
factors for HCC recurrence include the -fetoprotein level, tumor size, microvascular invasion,
gross major vessel invasion, bilateral tumor distribution, and histological differentiation. No
statistically significant difference was seen between cadaver donor and living donor LT in HCC
recurrence (76).
FIGURE 30-11. A 45-year-old man who underwent splenic artery embolization to control
splenic artery steal syndrome. A: Celiac arteriogram taken 3 days after transplantation
shows abundant flow into the splenic artery and relatively poor flow into the proper hepatic
artery (black arrow). B: Celiac arteriogram taken after embolization of the splenic artery
using coils (white arrow) shows markedly improved flow into the proper hepatic artery
(black arrow).
TACE and percutaneous transhepatic therapy including radiofrequency ablation are used for
recurrent HCC, but no effective response has been observed in most patients, probably due to
immunosuppressive therapy. Recurrent HCCs in a graft usually show rapid growth compared to
the nontransplanted liver (Fig. 30-10).
Arterial Embolization for Splenic Artery Steal Syndrome

Patients with chronic liver disease and portal hypertension often exhibit a hyperdynamic
vascular state. Increased total splanchnic blood flow toward the spleen results from lower
splenic arteriolar resistance and enlarged splenic artery. Liver transplantation does not cause
an immediate reduction in the total arterial flow in the spleen or the splenic parenchymal volume
in patients with pre-existing increased splenic arterial flow. Instead, most of the celiac blood
flow is diverted into the spleen, depriving the liver of a significant amount of arterial blood flow.
Furthermore, certain events such as preservation injury, rejection, or hepatitis can aggravate
this condition because these increase the intrahepatic arterial resistance. As a result, further
diversion of blood flow away from the hepatic artery occurs, causing further increased blood
flow in the splenic artery. If there is a significant reduction in intrasplenic arterial resistance,
whether or no associated with some degree of increased hepatic arterial resistance, a steal
phenomenon of the blood into the splenic artery may develop, predisposing to biliary damage
and liver failure. This combination of liver failure, reduced hepatic arterial perfusion (without
hepatic arterial occlusion), and steal of the arterial blood into the splenic circulation has been
called splenic artery steal syndrome (77). This phenomenon is more serious with small-sized
grafts. The incidence is reported to be 5.9% after whole-size LT and presents with elevated
liver enzymes, impaired graft function, or cholestasis (78).
Surgical splenectomy, splenic artery ligation, and reanastomosis of the graft hepatic artery with
an interposed vascular graft from the aorta are more complicated surgical techniques, whereas
splenic artery embolization is a simple and preferred therapeutic method to treat splenic artery
steal syndrome (79,80) (Fig. 30-11). However, a relatively large number of coils has to be used
for the embolization of the splenic artery. There are many reports of successful coil
embolization of the splenic artery with or without embolization of the gastroduodenal artery.
Clinical improvement was also reported after splenic artery embolization (77,81,82).

TIPS is indicated in the chronic stage of LT for the control of portal hypertension with a patent
portal system. TIPS is not technically difficult in whole-size LT with end-to-end anastomosis of
the IVC and LDLT. Although there have been several reports of successful results, technical
difficulties have been reported in piggyback caval-to-caval anastomosis (83,84). Close immune
suppression monitoring is suggested because of the modified metabolization of cyclosporine
and perhaps tacrolimus as well.
VASCULAR INTERVENTIONS FOR DONORS

The greatest concern is the risk of death to the living donor. Mortality of the right lobe donor
has been reported to be about 0.3% (85), and eight donor deaths have been reported
worldwide (86). Complications in the living donor are the same as with partial hepatic resection.
They include pleural effusion,
intraperitoneal fluid collection, bleeding, portal vein stenosis and kinking, and bile leak from the
cut edge of the liver. The incidence of major complications was reported to be 5% in patient
receiving hepatic resection, which is similar to that for liver donors (87).
The overall complication rate at AMC was 13.5% for 386 living donors, slightly higher in right-
lobe donors than left-lobe donors (88). Forty-eight percent of complications were effectively
treated with medical treatment alone, and surgical management was required in only 4%. The
remaining 48% of complications were treated by radiological interventions including
percutaneous drainage and aspiration, embolization for arterial bleeding, percutaneous
transhepatic biliary drainage and biliary stricture dilatation, and portal vein stent placement. We
have not had any donor death in >1,000 cases of LDLT at AMC.
If portal vein kinking is found during operation, stent placement through the mesenteric vein is
indicated for preservation of portal flow and for prevention of thrombosis. Portal vein stenosis
may be found several days after operation and percutaneous stent placement is a good
treatment modality. When there is portal vein stenosis combined with total thrombosis of the
portal vein, we believe that surgical re-exploration for thrombectomy and stent placement is the
best way to solve this situation. Portal vein stent placement in donors shows an excellent
patency during long-term follow-up in our experience.
ACKNOWLEDGMENTS
We would like to thank Sung-Gyu Lee, M.D., a LT surgeon at AMC, who provided descriptions
of the surgical techniques and a surgeon's view of the interventional management of LT. We
would also like to thank Sang Joon Park, M.D., Department of Radiology, Kang Dong Sacred
Heart Hospital, Hallym University, for editorial assistance in preparing the manuscript.
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> Table of Contents > Section III - Vascular Interventions > Part D: - Venous Access > Chapter 31 - Central Venous Access
Chapter 31
Central Venous Access
Hani Abujudeh
David W. Trost
There has been growing demand for central venous catheter use since the description of right
atrial indwelling catheters by Broviac et al. in 1973 and Hickman et al. in 1979 (1,2). This
mirrors the expanding needs in modern medicine for hemodialysis, long-term antibiotic therapy,
hyperalimentation, chemotherapy, plasmapheresis, and administration of blood products and
blood drawing as well as the drive toward outpatient treatment (3). Access to the superior vena
cava, right atrium, or inferior vena cava (IVC) enables the delivery of medicines at higher flow
rates compared to peripheral veins and reduces the risk of damage to smaller peripheral veins
by caustic formulations such as chemotherapy.
As a result of this growth, there is an increasing demand for more rapid and accessible venous
access services. Historically a service provided by surgeons, the benefits of imaging guidance
coupled with advances in minimally invasive techniques and toolsnamely, shorter procedure
times, fewer complications, and avoidance of the operating roomhas made venous access a
major constituent of the interventional radiologist's practice (4, 5, 6).
DEVICE SELECTION
Selection of the device is governed by the type and expected duration of therapy, frequency of
access, number of lumens required, flow-rate requirements, and patient and health care
provider preference. Central venous catheters may be inserted in peripheral or central veins;
may consist of one, two, or three lumens; may be tunneled subcutaneously; and/or may have a
subcutaneous port (Fig. 31-1).
Device construction has evolved over the past several decades. Silicone rubber and
polyurethane are the two primary materials used in current catheters. The advantage of silicone
is its biostability, i.e., it is resistant to developing bio-induced cracks, which can lead to device
failure. Polyurethanes, however, can be constructed with thinner walls (and, hence, a larger
internal-to-external diameter) compared to silicone (7). Some polyurethanes, on the other hand,
exhibit less biostability.
Catheters with different tip designs are also offered. The most common type is an open end-
hole tip that may be trimmed and is available in one-, two-, or three-lumen configurations.
Staggered-tip catheters contain two lumens, with one tip extending several centimeters beyond
the other tip. This is particularly useful in hemodialysis, given the need for simultaneous
aspiration and infusion. However, occasionally one tip may be occluded by a thrombus or by the
adjacent vessel wall. At dialysis, reversal of flow may be employed to clear the occlusion; this
may result in unwanted recirculation (8). Recirculation may also be seen with symmetric dual-
lumen hemodialysis catheters. A special symmetric dual-tip design (Palindrome catheter; Tyco
Healthcare Group LP, Mansfield, MA) may circumvent this problem (9) (Fig. 31-2).
A third type contains a slitlike valve-tip. The slit-valve opens during aspiration or infusion, but
remains closed when not in use, preventing stagnant blood from remaining in the catheter
during nonuse (10). This eliminates the need for heparinized flushes, which is an obvious
advantage for patients with heparin allergies; however, the valve limits flow ratesa
disadvantage in dialysis and pheresis applications. Valve-tip catheters may be trimmed at the
hub and hence have a detachable external component (11).
Implanted ports are made of various materials including titanium and plastic. Titanium and
plastic are advantageous compared to stainless steel because of their lighter weight and
nonferromagnetic properties, although the expense of titanium and question of durability of
plastics during needle access are important considerations. Some mixture of these materials is
often employed in port construction.
DEVICE TYPES
Peripherally inserted central catheters (PICCs) are placed in an upper extremity vein and
terminate at the cavo-atrial junction when used for central venous access. They typically have
smaller diameters compared to centrally placed devices and are consequently more ideal for
frequent infusion-type therapies lasting days to weeks rather than high-flow applications such
as dialysis. They are available in single- or dual-lumen configurations; single-lumen PICCs often
have a larger diameter than individual lumens in a dual-lumen configuration; consequently,
single-lumen PICCs enable higher flow rates (Fig. 31-1D).
PICCs generally require less procedure time to place and are often better tolerated by patients
than centrally placed catheters. Although it may be more cost-effective for PICCs to be
inserted at the bedside by specially trained nurses, interventional radiology can achieve
successful placement when venous access is challenging (12, 13, 14). PICCs are also
associated with a lower incidence of complications such as pneumothorax and may be less
likely to cause central venous narrowing due to their smaller diameter and avoidance of central
venotomy compared to central placement. In the outpatient setting, PICCs demonstrate lower
infection rates than centrally placed catheters, although the difference may not be significant in
the hospitalized setting (15).
Centrally inserted venous catheters include nontunneled and tunneled external catheters as well
as subcutaneous ports. Nontunneled external catheters are often placed at the bedside, are
available in one-, two-, or three-lumen configurations, and are most often constructed with open
end-hole tips. Given their need for frequent maintenance as well as the relatively high risk of
infection, they are indicated mainly for short-term use (days to weeks) (Fig. 31-1A).
External centrally placed venous catheters may also be tunneled subcutaneously from the skin
exit site to the venous access site. Tunneled catheters are constructed with a Dacron cuff
in the tunneled portion, which incites fibrotic ingrowth over a period of 4 to 6 weeks, securing
the catheter and providing a barrier to infection. Some catheters may also have a silver-
impregnated cuff adjacent to the skin site specifically to serve as a barrier to infection, although
their efficacy has been questioned (16). They are available in single-, double-, and triple-lumen
as well as open end-hole and valve-tip configurations. These catheters also require frequent
maintenance due to their external portion. They are best suited for intermediate-term use
(weeks to months), although they may also be employed for long-term applications. Dual-lumen
large-diameter configurations with open end-hole or staggered tips that enable high flow rates
are suitable for hemodialysis (Fig. 31-1B).
FIGURE 31-1. Assorted catheter images. A: Nontunneled pheresis catheters. Top: Schoen
XL catheter (Angiodynamics, Queensbury, NY). Bottom: Mahurkar Qplus catheter (Tyco
Healthcare Group LP, Mansfield, MA). B: Tunneled catheters. Top: More-Flow catheter
(Angiodynamics). Middle: PASV catheter (Boston Scientific, Natick, MA). Bottom: Cook
double-lumen catheter (Cook, Inc., Bloomington, IN). C: Assorted implanted ports, all from
Bard Access Systems (Salt Lake City, UT). D: Picc Line-Power Picc (Bard Access
Systems).
FIGURE 31-2. Pheresis catheter tips. Left: HemoSplit (Bard Acccess Systems, Salt Lake
City, UT). Middle: More-Flow (Angiodynamics, Queensbury, NY). Right: Palindrome (Tyco
Healthcare Group LP, Mansfield, MA).
Subcutaneous port catheters contain a subcutaneous reservoir connected to a catheter that is

tunneled to a central venous access site. Ports are traditionally implanted in the chest wall,
although smaller extremity ports with access through an upper extremity vein are available.
Ports are most often used for applications requiring low-frequency and long-term access
(months to years), such as for chemotherapy applications as well as blood product
administration and blood drawing. Port access is achieved by puncture with a noncoring needle
through a compressed silicone disk. They require less frequent maintenance, are better
tolerated by patients, and are more compatible with active lifestyles then external catheters,
although they require longer procedure times. It is debatable whether ports exhibit lower
infection rates than external centrally placed catheters (17,18) (Fig. 31-1C).
PERIPHERALLY INSERTED CENTRAL VENOUS DEVICES

Venous drainage of the upper extremities is composed of the larger superficial venous system
(basilic, cephalic, and median cubital veins) and the smaller deep venous system (radial, ulnar,
and brachial veins). The largest, most superficial vein is the basilic, which is consequently the
first choice for venous access. The cephalic vein is also suitable for venous access but is more
prone to venospasm. Accessing one of the paired brachial veins is less ideal given the proximity
to the brachial artery and nerve structures, although this risk is diminished by the use of
ultrasound guidance.
Technique
Ultrasound or, alternatively, fluoroscopy with iodinated or CO2 contrast can be used for venous
puncture and/or catheter placement. It is preferable to place PICCs in the nondominant arm;
cellulitic areas should be avoided. Access should be made above the level of the elbow to
prevent possible catheter kinking and improve patient comfort.
Access should be obtained using sterile technique and with the arm abducted. A venogram by
contrast injection of a distal forearm intravenous line may be performed to assess venous
anatomy and patency. After contrast is injected, a tourniquet may be applied to improve
contrast opacification. Ultrasound may also be used to survey the upper extremity veins;
tourniquet application may improve visualization by distending veins. Local anesthesia at the
puncture site should be conservative to reduce the risk of venospasm. If the brachial vein is to
be accessed, ultrasound can be helpful in preventing inadvertent arterial puncture.
Needle puncture should be performed parallel and 30 to 45 degrees to the anterior wall of the
vein. Small (100- to 200-g) aliquots of nitroglycerin may be administered if there is significant
venospasm. An 0.018-in. guide wire is inserted; the dermatotomy is extended and a peel-away
sheath is inserted. The guide wire is advanced to the cavo-atrial junction. Clamping or kinking
the guide wire at the exit site can serve as a marker for catheter length. The PICC is cut to the
appropriate length based on the length of the guide wire from the clamp/kink to the tip. The
PICC is flushed, the dilator of the peel-away sheath is removed, and the PICC is inserted
through the sheath. Position is confirmed by fluoroscopy. The sheath is peeled away and the
hub is then sewn to the skin with nonabsorbable sutures. The PICC should then be flushed with
heparinized solution.
Upper Extremity Subcutaneous Port

Upper extremity ports are smaller than their chest wall counterparts and may be less
conspicuous. They have a low risk of infection and are less likely to lead to pneumothorax
during insertion compared to chest wall ports (19, 20, 21). However, there may be a higher risk
of deep venous thrombosis with arm as compared to chest ports (22). Insertion of the catheter
portion is similar to PICCs as described previously, although antibiotic prophylaxis is
administered within 1 hour of placement. A venogram is performed to verify central venous
patency.
After administration of local anesthesia near the puncture site, a skin incision is made and a
small subcutaneous pocket is created by blunt dissection. The pocket should be constructed
approximately 0.5 to 2 cm under the skin to prevent erosion by and optimize future needle
accessibility of the port. The flushed catheter and port are connected. The port is then retained
by medial and lateral nonabsorbable sutures and fully inserted into the pocket, positioned so
that the suture line will not overlie the diaphragm of the port. The position of the port and
catheter is confirmed fluoroscopically and is then aspirated and flushed with heparinized
solution. The skin incision is closed with running subcuticular stitches using absorbable sutures.
If immediate use is desired, the port can be accessed with a 0.5- in. Huber needle.
CENTRALLY INSERTED CENTRAL VENOUS DEVICES

Centrally inserted venous catheters include externalized nontunneled and tunneled catheters as
well as subcutaneous chest wall ports.
Access
The axillary, subclavian, and internal jugular veins are the primary access sites. Complications
associated with central venous accessnamely, pneumothorax and central vein stenosisare
less frequent with internal jugular compared to subclavian vein catheter placement (23). The
right and left internal jugular veins should be considered over the right and left subclavian veins.
Although anatomic landmarks may be used to guide access, imaging guidance is advantageous
in reducing procedural complications and confirming venous patency (24,25).
Ultrasound guidance with a high-frequency transducer or venography may be used. Venous
patency, visualization of surrounding soft tissues and adjacent artery, and reduction of contrast
and radiation use are advantages of ultrasound use. Needle guidance is best achieved with
longitudinal imaging, whereas maintaining both venous and arterial perspective is best
performed with transverse imaging (26). Venography may be used to guide access as with
peripheral insertions of catheters; contrast is injected through a peripheral vein. Imaging
guidance is especially important in preventing inadvertent arterial puncture when micropuncture
technique is used, as pulsatile arterial flow may not be seen when a small-gauge needle is
used.
As with peripherally inserted central catheters, sterile technique is required. To reduce the risk
of air embolism, the patient should suspend respiration, perform a Valsalva maneuver, or hum
when an open sheath, dilator, or catheter is in the vein.
Internal Jugular Vein

To enable a gentle curve in the catheter's course, a posterior approach is employed. Using
ultrasound or venography, the vein is punctured with a small-gauge needle, then an 0.018-in.
guide wire is inserted and should be advanced to the right atrium to verify venous system
access. The needle is exchanged for a dilator and peel-away sheath.
Axillary/Subclavian Vein
The axillary vein transitions into the subclavian at the lateral aspect of the first rib. An important
goal of axillary/subclavian access is to ensure that the catheter has entered the vein lateral to
the first rib-clavicle junction. More medial placement increases the risk of pinch-off syndrome, in
which a catheter traversing the subclavius tendon and costoclavicular ligament is compressed
during arm motion, leading to catheter fracture (27,28).
A small-gauge needle is oriented 45 degrees to the vein under imaging guidance. After
puncture, an 0.018-in. guide wire is inserted and advanced to the right atrium. As with internal
jugular puncture, the needle is exchanged for a dilator and peel-away sheath.
Nontunneled and Tunneled Catheters

Nontunneled catheters are usually rigid and are indicated for short-term (days to weeks) use.
They should be trimmed such that they terminate at the cavo-atrial junction or high right atrium.
Length can be estimated as with PICC placement: the guide wire should be advanced to the
cavo-atrial junction or high right atrium and the wire clamped or kinked where it exits the access
site. The guide wire is then used as a template for measuring and trimming the catheter. The
catheter is then advanced through the sheath and the position confirmed fluoroscopically. The
sheath is peeled away and the catheter is secured to the skin with nonabsorbable sutures (29).
Nondialysis tunneled catheters will have a Dacron cuff which promotes securement of the
catheter by fibrous ingrowth over several weeks. As a result, the position of the cuff needs to
be considered when measuring catheter length. A guide wire is again used as a template, with
its tip in the high right atrium. The catheter is then trimmed such that the Dacron cuff will be
positioned 1 to 2 cm from the tunnel exit site.
After venous access is established, the exit site in the anterior chest wall is prepared. The exit
site is usually chosen inferior to the clavicle, avoiding breast tissue. Local anesthesia is applied
in the region of the exit site and along the planned subcutaneous tunnel. An incision is made at
the exit site and a tunnel tool is used to bluntly dissect the subcutaneous tissue to the venous
access site.
The catheter is then attached to the tunnel tool and brought subcutaneously from the chest wall
exit site to the venous access site. The catheter is flushed and locked, the inner dilator and
guide wire are removed, and the catheter is inserted through the sheath during suspended
respiration. Position is confirmed fluoroscopically. The venous access site may be closed with
Steri-Strips or absorbable or nonabsorbable sutures. Securement of the external catheter at
the chest wall exit site may be performed using sutures or retainers included in the catheter kit.
The catheter is flushed with heparinized solution and a postprocedure chest radiograph is
obtained to screen for pneumothorax.
FIGURE 31-3. A: An x-ray of a patient with a double-lumen port entering from the right
internal jugular vein. B: An x-ray of a patient with a tunneled catheter entering from the
right internal jugular vein.
Subcutaneous Port
The port is placed in the anterior chest wall, far from the clavicle to prevent contact, and away
from breast tissue. A skin incision is made after application of local anesthesia and the
subcutaneous tissues are bluntly dissected. The pocket should be just large enough to fit the
port without allowing subsequent sutures to overlie the diaphragm. Approximately 0.5 to 2 cm
of tissue should overlie the port, leaving sufficient subcutaneous tissue to prevent port erosion.
Too much tissue may make subsequent needle access difficult. Hemostasis is achieved by
saline irrigation and/or wet gauze. The port is secured on its medial and lateral sides with
nonabsorbable sutures. Because fibrotic fixation of the port will develop, absorbable sutures
can also be used.
After local anesthesia is applied to the planned tunnel route, blunt dissection of subcutaneous
tissues is performed from the venous access site to the pocket. The catheter is then attached
to the tunnel tool and pulled from the venous access site to the pocket. The catheter is
attached to the port, flushed, and trimmed; as described previously, the guide wire can be used
as a template. The catheter is inserted into the sheath, which is peeled away, and fluoroscopy
is performed to confirm position and absence of kinks. The port is accessed with a noncoring
needle, blood is aspirated, and the catheter is flushed with heparinized solution. The venous
access site is closed with Steri-Strips or absorbable or nonabsorbable sutures. The
subcutaneous layer of the pocket is closed with absorbable sutures, followed by a running
subcuticular sutures and Steri-Strips. A postprocedure radiograph is obtained to screen for
pneumothorax (Fig. 31-3A).
FIGURE 31-4. A: Tunneled catheter entering through the right common femoral vein. B:
Implanted port entering through the inferior vena cava.
Hemodialysis
The right internal and external jugular veins, followed by the left internal and external jugular
veins, should be considered for hemodialysis access. Subclavian access is discouraged, as
stenotic complications from catheter placement may comprise future planning for upper
extremity permanent access (e.g., arteriovenous shunt). Hemodialysis catheters may be
nontunneled or tunneled. Venovenous dialysis requires high flow rates; hence, dialysis catheters
are of large diameter and are duallumen. Tunneled hemodialysis catheters should be placed in
the right atrium to reduce the risk of superior vena cava stenosis and to maximize blood flow
(Fig. 31-3B).
Alternative Access
Occasionally, central venous access through the axillary, subclavian, or internal jugular veins is
not possible. The femoral vein can be utilized for access, however, there is an increased risk of
infection (Fig. 31-4A). The IVC can be used for alternative access, and a translumbar or
transhepatic approach may be taken. Another possibility includes direct hepatic vein catheter
placement. In addition, access through collateral or occluded vessels may be performed.
External catheters as well as implantable subcutaneous ports may be placed. Indeed,
alternative access may demand creative energies from the interventional radiologist.
Infrarenal Inferior Vena Cava

Access to the infrarenal IVC may be achieved through a translumbar approach (30, 31, 32).
Although fluoroscopy is often used for imaging guidance, computed tomography (CT) guidance
or, in pediatric cases, ultrasound visualization of the IVC can be performed. Preprocedure CT is
helpful to assess venous anatomy and patency, abdominopelvic anatomy and pathology (e.g.,
abdominal aortic aneurysm), and optimal needle insertion site.
The patient is placed prone, left anterior oblique (LAO), or in the left lateral decubitus position.
A guide wire may be placed in the IVC via transfemoral approach to serve as a landmark.
Otherwise, the needle insertion site is chosen just superior to the right iliac crest and
approximately 8 to 10 cm lateral to the verterbral midline in adults. A small-gauge, diamond-
tipped needle is angled 45 degrees cephalad and advanced to the L3 vertebral body. Cephalic
angulation of the needle will prevent sharp angulation of the catheter as it enters the IVC. The
needle is retracted, angled more laterally, and advanced anterior to the vertebral body. The
stylet is removed and blood should subsequently be aspirated as the needle is slowly retracted.
An 0.018-in. guide wire is subsequently inserted, with subsequent fluoroscopic confirmation of
venous system access (Fig. 31-4B).
Suprarenal Inferior Vena Cava

A subcostal or intercostal transhepatic approach to the suprarenal IVC is another option for
central venous access (33). The subcostal approach is especially amenable to ultrasound
guidance. After ultrasound survey of the liver and IVC, a needle is guided directly to the IVC;
the stylet is removed and blood aspirated as the needle is retracted. Alternatively, an
intercostal approach may be performed similar to transhepatic cholangiography.
The suprarenal IVC may also be accessed indirectly via a hepatic vein. Central venous access
obtained in this approach is mostly seen in children with short-gut syndrome in need of long-
term parenteral nutrition. The approach maximizes the intravascular length of catheter, which
reduces the risk of catheter dislodgement during subsequent rapid growth in these children. The
right, left, or middle hepatic vein may be used; the middle vein is often chosen given it anterior
course. Ultrasound-guided needle puncture of the hepatic vein is performed using a subcostal
approach; blood is aspirated, and the catheter is placed as described above.
Collateral Vessels
Charting collateral vessels may be performed using fluoroscopic, CT, or magnetic resonance
venography. The collateral vessel to be accessed may be punctured directly using ultrasound
guidance or fluoroscopic venography (34). Alternatively, a gooseneck snare technique can be
employed (35). In this technique, a gooseneck snare is placed in the collateral vessel via
peripheral access; the open snare then serves as target for direct puncture using fluoroscopic
guidance. As with collateral vessels, the azygous and intercostal veins may also serve as
alternative routes for central venous access (36, 37, 38).
Occluded Vessels
Revascularization techniques may be employed to obtain access through occluded venous
segments (39, 40, 41). A guide wire may be inserted proximal to the central venous
obstruction. Sometimes, a snare introduced through a femoral approach may be necessary to
bring the guide wire completely through the occlusion (41). Standard thrombolysis and/or
revascularization techniques using angioplasty and stenting can then be employed.
COMPLICATIONS
One of the impressive strengths of interventional radiologic placement of central venous
catheters is the reduced complication rate compared with blind bedside or surgical placement
(3,13,25,42,43). However, despite advancing tools and techniques, a variety of complications
may occur in approximately 7% of patients during short- or long-term follow-up (3).
Short-term complications occur within 30 days of central venous catheter placement (3).
Examples include failure to achieve access or placement, air embolism, pneumothorax, vessel
injury and hematoma, hemothorax, and cardiac injury and/or arrhythmia. Long-term
complications occur 30 days after catheter placement. Examples include catheter and/or vessel
occlusion/stenosis, catheter malposition, catheter fracture and fragment embolization, and
infection.
Short-Term Complications
The rate of failure of access and secure catheter placement is very low, typically not exceeding
5% (3). The low rate of failure reflects the extraordinary benefit of imaging guidance, not only
for securing the targeted access, but also for enabling the interventional radiologist to choose
alternative targets inaccessible to blind techniques.
Catheter malposition is also rare with imaging guidance. Catheter tips should be placed at the
cavo-atrial junction or high right atrium (44). Tips that are placed more distal may irritate the
cardiac wall and induce arrhythmia, may perforate the cardiac wall, or may cause valvular
damage. Placement too proximal may lead to catheter dysfunction as the tip is occluded by the
vessel wall. The approach to arrhythmias is catheter repositioning or removal and standard
advanced cardiac life support (ACLS) protocol. A longer catheter should be used in patients
with a large amount of breast tissue since the catheter may retract when the patient sits or
stands.
Air embolism is a procedural complication that may occur in 1% of patients (3). Negative
intrathoracic pressures result during inspiration; air may be aspirated if the venous system is
open to atmosphere, such as with an open sheath (45). It may be associated with a 50%
mortality (25). This may be prevented by asking the patient to suspend respiration, to perform
a Valsalva maneuver, or to hum in an effort to create a positive intrathoracic pressure, although
increased bleeding at the access site may occur. Pinching the sheath may also prevent air
aspiration. Air embolism may manifest with dyspnea, hypoxia, and agitation and progress to
right heart failure and shock. Once suspected, the patient should be put in the lateral decubitus
position to allow the aspirated air to rise antidependently in the right atrium. If possible, the
pockets of air should be aspirated with a catheter.
A pneumothorax may occur when the pleura is punctured, and is more common during attempts
at subclavian vein access, especially without imaging guidance. With imaging guidance, the rate
is low, typically 1% to 2% for centrally inserted catheters and virtually zero for PICCs (3). When
pneumothoraces do occur, they are often small and asymptomatic; such patients should be
followed clinically and with serial upright chest radiographs for 8 hours. Larger or symptomatic
pneumothoraces require a chest drain or tube. Especially large pneumothoraces may require a
surgical consult.
A hemothorax is a potential complication when small or large vessels are disrupted, and may
occur in 1% of centrally inserted catheters (3). As with pneumothoraces, conservative therapy
with hemodynamic observation is sufficient for a small and asymptomatic hemothorax;
otherwise, a chest drain or tube with possible surgical consult may be needed. Vascular injury,
whether arterial or venous, may also lead to hematoma formation. Imaging guidance and
preprocedural correction of coagulopathy or reversal of therapeutic anticoagulation minimizes
the sequelae of vessel wall injury. Manual compression and occasionally employment of
embolization techniques may be necessary. The latter may be especially important when
adjacent arterial and venous injury leads to arteriovenous fistula formation.
FIGURE 31-5. Twiddler's syndrome. This patient had an IVC port placed. She returned
with a dysfunctional port. The x-ray shows that the port catheter wound up in the
subcutaneous port pocket.
Long-Term Complications
Subsequent imaging even long after catheter placement may demonstrate new catheter
malposition. The catheter tip may move proximal or distal and/or may be lodged in a venous
tributary. Such catheter migration may occur with vigorous exercise, cough, or emesis or may
be due to a large amount of breast tissue that, when the patient sits or stands, causes the
catheter to retract. Occasionally, due to inadvertent external manipulation by the patient and/or
large pocket size, subcutaneous ports may also rotate or flip, otherwise known as Twiddler's
syndrome (46) (Fig. 31-5). The use of catheters of appropriate length and the creation of
subcutaneous pockets so as to just fit the port are important preventive measures as discussed
previously. When migration of catheters occurs, forceful injection of saline may dislodge the
catheter tip. Alternatively, a transfemoral snare technique may be useful in repositioning the
catheter. Otherwise, catheter exchange or new access may be required.
Catheter fragmentation and embolization is another potential complication, particularly of
subclavian central venous catheters. Fragmentation is often the end result of pinch-off
syndrome (27,28,47) (Fig. 31-6). A subclavian central venous catheter placed medial to the
junction of the first rib and clavicle may traverse the costoclavicular ligament and subclavius
tendon. It may then be subject to repeated entrapment, with subsequent catheter fatigue and
fragmentation. The fragment may embolize to the right atrium, right ventricle, or pulmonary
artery. Foreign body retrieval techniques, such as with a gooseneck snare or Dotter retrieval
basket, may then be used to remove the fragment. If subclavian access is necessary, the
catheter should enter the vein lateral to the first rib-clavicle junction.
FIGURE 31-6. Catheter pinch-off syndrome. A: Disruption of an infusion port catheter in
the region of the subclavius tendon (black arrow). B: Contrast extravasation at the site of
disruption. C: Image obtained 2 days later, demonstrating complete fracture of the
catheter.
Most central catheters will develop an enveloping fibrin sheath, which may grow to encompass
the catheter tip, leading to catheter dysfunction (48) (Fig. 31-7). Classically, one may not be
able to aspirate blood from the catheter while having no difficulty injecting or infusing through it.
Under fluoroscopy, injected contrast may be seen to flow retrograde along the catheter.
Traditionally, fibrin stripping with transfemoral snare techniques has been employed (49),
although insertion of a guide wire through the catheter to fragment the distal fibrin should be
performed first. If these efforts are unsuccessful, catheter exchange should be attempted.
Catheter and venous thrombosis occurs in up to 3% of PICCs and 4% of centrally inserted
catheters. Thrombosis may be asymptomatic or may manifest as edema and/or pain in the
neck, arm, and/or chest. The probability of thrombosis is related to multiple factors such as the
position of the catheter and duration of placement, hypercoagulability, and infection (44).
Catheter thrombosis may be treated with injection of an aliquot of urokinase, allowing it to dwell
for 30 minutes, followed by aspiration. Infusion of urokinase is also an option (44,48,50).
Similarly, thrombolytics may be employed in venous thrombosis. Recombinant tPA has also
been used with success. Systemic anticoagulation may be used in patients with limited
alternative access. Low-dose coumadin (1 mg per day) is a preventive measure (50,51).
Catheter removal is required in cases that are complicated by infection.
FIGURE 31-7. Fibrin sheath around the catheter tip. The sheath is outlined by the small
arrows.
An often challenging complication of central venous catheters is infection, which may involve the
exit site or the tunnel or pocket or may manifest as sepsis. Risk factors for infection include
lack of strict sterile technique during catheter access, immunosuppression, and multiple-
catheter lumens.
Patients with infections may exhibit erythema and edema at the catheter exit site. Oral
antibiotics and topical care are usually successful in eliminating the infection. In patients with a
tunneled catheter or port, pus expressible from the exit site or that accumulates within the
pocket may occur. Catheter removal and intravenous antibiotics are usually required. A
bacteremic patient without evidence of exit-site or tunnel/pocket infection may develop fever
and leukocytosis; such patients may be assumed to have catheter-related sepsis when no other
source is identified. A more definitive diagnosis is made when blood cultures drawn from the
catheter exhibit at least a 10-fold higher number of bacterial colonies compared to blood
cultures drawn at another site. As with tunnel/pocket infections, catheter removal and
intravenous antibiotics are required.
CONCLUSION
There is an ever-increasing demand for a venous access service that is readily available, quick,
and reliable. The advances in interventional techniques and tools, coupled with the creativity of
practitioners, have propelled venous access service to become a major core of the
interventional radiologist's practice. Detailed knowledge of devices, mastery of the skills
required to place them, and maintenance of responsibility for follow-upparticularly in
complicated casesare the crucial elements in establishing a successful venous access
service.
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> Table of Contents > Section III - Vascular Interventions > Part E: - Embolotherapy: AVM, Tumors, and Trauma > Chapter 32 -
Peripheral Vascular Malformations
Chapter 32
Peripheral Vascular Malformations
Jeffrey S. Pollak
Robert I. White Jr.
Vascular anomalies encompass a variety of different lesions occurring in many organs and with
varying clinical manifestations, from asymptomatic to disfiguring and even life-threatening. In the
past, a better understanding of these entities was hampered by the lack of appropriate and
consistent classification, with the word hemangioma, in particular, often used incorrectly (1).
In a landmark paper in 1982, Mulliken and Glowacki (2) drew a distinction between
hemangiomas and vascular malformations based on endothelial cell characteristics. The former
are endothelial neoplasms with cellular proliferation, while the latter are developmental
abnormalities and generally do not have increased endothelial cell proliferation. Vascular
malformations may originate from the arterial, capillary, venous, or lymphatic systems or a
combination of these. Based on these biological distinctions, the International Society for the
Study of Vascular Anomalies adopted a classification system in 1996, which serves as the
basis for Table 32-1 (1,3, 4, 5). Malformations may also be considered high-flow or low-flow,
which is particularly important for therapeutic decisions. Only lesions with an arterial or AV
component are high-flow.
An alternate classification system based on anatomic and developmental characteristics was
adopted at the 7th Meeting of the International Workshop on Vascular Malformations in
Hamburg, Germany, in 1988 (6,7) (Table 32-2). This categorizes malformations based on the
vascular bed (species), whether the lesion arises in an embryologically differentiated vascular
truncus (truncular malformation) (e.g., coarctation of the aorta) or from the earlier primitive
capillary network (extratruncular), and morphological characteristics such as obstruction or
dilatation for truncular lesions and infiltrating or limited for extratruncular lesions. A potential
area of confusion is distinguishing between normal variants and truncular malformations.
The vast majority of peripheral, superficial vascular anomalies can be appropriately identified
with history and physical examination (8,9). Imaging studies are usually not necessary for
diagnosis but are important for defining the extent of disease. Biopsy is rarely needed, although
it is important when a malignancy is suspected. Once classified, the prognosis and need for
therapy can more easily be determined as a clearer understanding of the natural history of
each lesion has emerged. This chapter focuses on vascular anomalies outside of the central
nervous system. Due to their varied locations, structural and hemodynamic effects on other
organs, and the different types of therapies needed, multiple specialties are often needed to
manage patients with these lesions, including plastic surgery, orthopedic surgery, pediatric
surgery, vascular surgery, dermatology, interventional radiology, and organ specialists specific
to the location and systemic effects of a lesion.
VASCULAR TUMORS
While a thorough discussion of vascular tumors is not within the scope of this chapter, an
overview is necessary with regard to their distinction from vascular malformations.
Hemangioma is a benign vascular neoplasm, with the infantile form (IH) being the most common
benign tumor in children (10, 11, 12). Most are sporadic (not inherited) and they are more
common in girls. They appear within the first few months of life, with deeper lesions more likely
to present later. The head and neck is most commonly involved (60%), followed by the trunk
(25%) and the extremities (15%) (4). Visceral organ involvement also occurs (such as liver and
brain) and should be suspected if multiple visible IHs are present, as happens in 20% of cases.
Associated conditions may occur, with lesions distributed along the facial nerve (PHACE[S]
syndrome) and lumbosacral region (tethered cord) (12).
Infantile hemangioma progresses through three stages (3,5,10, 11, 12, 13). The proliferative
phase occurs in the first year and demonstrates rapid enlargement. Lesions are positive for
glucose transporter isoform 1 (GLUT1). Dermal lesions are firm, raised, noncompressible, and
often red, the classic strawberry mark, while deeper lesions are more subtle. The involuting
phase over the next 1 to 5 years sees slow regression of the now softer, paler tumor.
Complete regression is typical by 5 to 7 years. Most patients are left with nearly normal skin.
Imaging is helpful for lesions that are deeper, atypical, or located about critical structures and
for assessment of associated conditions (4,13). Studies show a well-defined, solid,
hypervascular (low resistance on ultrasound), homogeneously enhancing, lobular soft tissue
mass that generally (but not always) has no shunting to veins yet may have enlarged feeding
and draining vessels. Phleboliths may be present. Magnetic resonance imaging (MRI) is most
informative, with the mass of intermediate intensity on T1-weighted images and hyperintense on
T2-weighted spin-echo and inversion recovery ones (Fig. 32-1).
Treatment is needed in only 10% to 20% of IHs, for aggressive growth or critical location, such
as the orbit or airway (3,10, 11, 12). Up to 90% respond to corticosteroid therapy, with
interferon- or vincristine tried for the remainder. Resection is occasionally necessary.
Embolization is rarely needed (Fig. 32-1). Other measures include wound care for ulcerated
lesions and antibiotics for infection.
Hepatic hemangioma (also called hemangioblastoma) also involutes with time, but due to
serious, even life-threatening symptoms, therapy is more frequently indicated (12,14). Solitary
and multifocal involvement may give high output failure from shunting, while diffuse involvement
gives massive hepatomegaly without heart failure and occasional associated
hypothyroidism. Imaging studies reflect the presence of one or more liver masses with high-
flow vessels as well as enlarged feeding visceral arteries and subsequent tapering of the aorta
(14). Focal abnormal tissue signal helps distinguish them from the less common hepatic
arteriovenous malformation (AVM). Embolization of shunting lesions and/or surgery is
considered only if symptoms persist after pharmacological therapy. Embolization is best done in
stages, with attention to any portovenous fistulae, as arterial occlusion could then result in
extensive hepatic necrosis.
TABLE 32-1 CLASSIFICATION OF VASCULAR ANOMALIES BASED ON

THAT OF THE INTERNATIONAL SOCIETY FOR THE STUDY OF
VASCULAR ANOMALIES (1,3, 4, 5)
Vascular tumors
Infantile hemangioma
Congenital hemangioma
Rapidly involuting congenital hemangioma
Noninvoluting congenital hemangioma
Kaposiform hemangioendothelioma
Tufted angioma
Pyogenic granuloma (lobular capillary hemangioma)
Hemangiopericytoma
Angiosarcoma
Vascular malformations
Simple
Low-flow
Capillary (CM; port-wine stain)
Venous (VM)
Lymphatic (LM)
Microcystic (lymphangioma)
Macrocystic (cystic hygroma)
Combined or mixed
High-flow
Arterial (AM) and arteriovenous (AVM) (including congenital AVF)a
Combined
Low-flow
Lymphatic-venous (LVM)
Capillary-lymphatic-venous (CLVM; includes Klippel-Trenaunay syndrome)
Capillary-venous (CVM; includes milder cases of Klippel-Trenaunay

syndrome)
Cutis marmorata telangiectatica congenital
High-flow
Arteriovenous malformation (AVM; including congenital AVF)a
Capillary-arterial-venous (i.e., with arteriovenous shunting; CAVM; Parkes

Weber syndrome)
a Arteriovenous malformation is often considered as part of the spectrum of arterial
malformation rather than as a combined malformation.
Kaposiform hemangioendothelioma (KHE) is a vascular tumor of borderline malignancy that is

commonly present at birth, is GLUT1 negative, is most often located in the trunk, extremities, or
retroperitoneum, and is solitary (5,15,16). It is frequently associated with Kasabach-Merritt
syndrome (KMS), in which platelet trapping results in thrombocytopenia, petechiae, and
bleeding. On MRI, KHE has similar features to IH but will lack a well-defined margin, involve
multiple contiguous tissue layers, have smaller feeding and draining vessels relative to tumor
size, may have signal voids perhaps related to hemosiderin, and may occasionally have
adjacent osteolysis (15).
The mortality rate for KHE is as high as 30% (10,15). Pharmacological and supportive
measures are first-line therapies. Heparin is ineffective and contraindicated, as it can worsen
tumor growth and hemorrhage. Surgery may be feasible for limited lesions. Radiation therapy is
occasionally needed. Embolization may also occasionally have a role, especially in more
localized lesions, but it appears to be of limited durability.
PERIPHERAL VASCULAR MALFORMATIONS

Since vascular malformations are developmental abnormalities, they or their underlying defect
are considered to be present at birth, even if not clinically evident. These disorders arise in the
embryo between the fourth and the tenth weeks and are usually not inherited (4). They
generally have an equal sex distribution and grow commensurate with the individual, although
clinical worsening can occur in the setting of trauma, hormonal changes, such as puberty and
pregnancy, infection, and spontaneously. Vascular malformations show normal cell growth and
structure, with slow turnover, a flat intima, and a thin basement membrane (2). Low-flow
malformations predominate over high-flow ones, with the latter accounting for <10% of all non-
central nervous system (CNS) congenital vascular malformations (17). Confusion about the
exact incidences of each type are related to the difficulty in using older literature, where
hemangioma is often used to describe malformations, and the two different classifications used
in more current literature (Tables 32-1 and 32-2). Unfortunately, the terms vascular
malformation and AVM are also often used to describe acquired lesions in various organ
systems such as the gastrointestinal tract (18), also adding to the confusion.
TABLE 32-2 CLASSIFICATION OF VASCULAR MALFORMATIONS BY THE

INTERNATIONAL WORKSHOP ON VASCULAR MALFORMATIONS (6,7)
Form
Species Truncular Extratruncular
Predominantly arterial Obstruction (aplasia and stenosis) Infiltrating
Dilatation (diffuse and localized

Limited
aneurysm)
Predominantly venous Obstruction (aplasia and stenosis) Infiltrating

Dilatation (diffuse and localized
Limited
varix)
Deep arteriovenous communications Infiltrating

Predominantly arteriovenous
shunting Superficial arteriovenous
Limited
communications
Predominantly lymphatic Obstruction (aplasia and stenosis) Infiltrating
Dilatation Limited
Combined or mixed Arterial and venous Infiltrating
Hemolymphatic Limited
FIGURE 32-1. A 47-year-old woman with a painful, biopsy-proven intramuscular right thigh
hemangioma. The mass is isointense to surrounding muscle on a transverse T1-weighted
spin-echo image (A) and enhances with some nodularity after contrast (B). It is
hyperintense on sagittal fast spin-echo inversion recovery image, with flow voids related to
vascular supply (C). Angiography confirmed a densely hypervascular mass with no AV
shunting (D). Two profunda femoral artery branches were embolized with a combination of
particulates and glue (E).
CAPILLARY MALFORMATIONS
Capillary malformations (CMs) are not uncommon, occurring at birth in 0.3% of children (19). In
addition to the skin, they often involve mucous membranes and may be localized or widespread
(10). The typical red or pink port-wine stain skin discoloration is often present at birth and
generally darkens with age, probably related to vessel dilation, and the lesions may also
become thicker and nodular (Fig. 32-2) (20). Pathologically, CMs consist of thin-walled ectatic
vessels in the papillary and upper reticular layers of the dermis (21). Possible associated
abnormalities include soft tissue and skeletal overgrowth and CNS vascular and developmental
anomalies. Perhaps the most well known is Sturge-Weber syndrome, occurring in 1% to 2% of
patients with CMs (22,23). This disorder consists of a cutaneous CM (occasionally with a
lymphatic malformation) typically in the distribution of ophthalmic division of the facial nerve
along with ipsilateral ocular and leptomeningeal vascular anomalies (usually capillary or
venous), which can result in glaucoma, cerebral calcification, and cortical atrophy, with seizures,
headaches, and neurological and cognitive deficits. When therapy is needed for cutaneous CM,
the mainstay is laser photocoagulation, with the pulsed dye laser preferred (10). Excision and
reconstructive procedures are occasional needed.
FIGURE 32-2. A 48-year-old man with Klippel-Trenaunay syndrome (discussed later in this
chapter) of his left thigh and buttock who has enlargement of the thigh, a longer left than
right lower extremity, scattered port-wine stains representing CMs (black arrows),
varicose veins (those about the knee indicated by white arrows), and more focally
prominent superficial venous malformations (one indicated by the open black arrow). (See
the color insert.)
Other conditions often considered with CM are salmon patch birthmarks (24) and
telangiectases. Telangiectases are seen in a variety of disorders, both malformations and
acquired. These consist of focally dilated small vessels that, on skin or mucosal surfaces,
appear as macules or papules and generally blanche with pressure. The vessel of origin is not
always certain, but at least in patients with hereditary hemorrhagic telangiectasia (hereditary
hemorrhagic telangiectasia), the mature lesion consists of direct arteriolar-venular
communications (25), which are likely tiny AVMs.
VENOUS MALFORMATIONS
Venous malformations (VMs) are low-flow lesions consisting of dilated, thin-walled, endothelial
lined, sponge-like channels of varying size that may show clot formation, fibrovascular ingrowth,
and phleboliths (20). Sparse smooth muscles cells are present in clumps rather than the more
uniform normal architecture. While they communicate with the rest of the venous system, the
degree varies from barely perceptible communication, giving rise to almost-isolated lesions, to
free communication, which is more likely with diffuse than focal lesions (7,26). Drainage may be
through normal or dysplastic, ectatic veins. On occasion, a VM may be combined with
lymphatic elements, giving a combined lymphaticovenous malformation (LVM). Aplastic and
dysplastic veins, with absent or incompetent valves, should also be considered in the spectrum
of VM (truncular forms). Older, incorrect names for VM are venous angioma, cavernous
angioma, and cavernous hemangioma.
Most VMs are sporadic but two forms with autosomal dominant inheritance have been
described (27). The first is linked to 9p21, gives rise to cutaneomucosal VM, and accounts for
~1% of true VMs. The second is linked to 1p21, gives rise to the noncompressible glomuvenous
malformation (glomangioma), which contains glomus cells (a type of modified smooth muscle
cell) and accounts for >60% of these lesions.
Although present at birth, VMs may not become clinically evident until later in life. They are
most common in the head and neck (40%), followed by the extremities (40%) and the trunk
(20%) (28). They vary from small and localized to diffuse and infiltrating and may be isolated or
multiple, raising suspicion for an inherited condition (20,27). Skin or subcutaneous tissue lesions
are most common and are soft, nonpulsatile, compressible, raised or flat lesions that are not
warm and often have a bluish discoloration (Fig. 32-3A). They expand with Valsalva,
dependency, and activity. Deeper involvement of muscle, bone, joints, and abdominal viscera is
common; clinical evaluation often underestimates disease extent (Fig. 32-3B) (29). While often
asymptomatic, VMs can result in stiffness, discomfort, pain, cosmetic concern, and,
uncommonly, hemorrhage with ecchymosis. Symptoms may be spontaneous, often in the
morning, or related to exertion, presumably from lesion and/or muscular engorgement, or
thrombosis, which can give an acutely firm, enlarged, painful mass. Additional consequences
include facial, ocular, and dental distortion and airway comprise with head and neck VMs as
well as associated intracranial VMs (20,26). Extremity lesions can give bony thinning and
demineralization with possible pathological fracture, limb undergrowth (typically slight and from
disuse), and joint effusions and hemarthrosis, which can lead to arthritis (4,20). Bowel
involvement can give chronic bleeding with anemia. Some believe liver hemangiomas in the adult
are actually VMs (12).
Blue-rubber bleb nevus (Bean) syndrome consists of numerous small, circumscribed VMs, most
commonly in the gastrointestinal tract and skin but possibly anywhere (30,31). This rare
syndrome is generally sporadic, but autosomal dominant inheritance has been described in
some. Chronic low-grade intestinal bleeding with anemia requiring transfusions is common.
Intussusception and volvulus may also occur. While traditionally managed conservatively with
iron and transfusions, operative intervention may offer promising results (30). Maffucci
syndrome is a rare noninherited condition consisting of enchondromas and nodular venous
lesions that are VMs possibly combined with spindle cell hemangioendotheliomas (20,32).
Malignant transformation develops in 15% to 56%, most commonly chondrosarcomas.
FIGURE 32-3. Foci of blue skin discoloration from the superficial component of a venous
malformation in a 12-year-boy with swelling over his lateral distal arm (A) (See the color
insert.). Both superficial (white arrows) and intramuscular (black arrows) disease is evident
on T1-weighted fat saturated MRI (B).(see color image)
Extensive, widely infiltrating VMs and LVMs can cause a chronic localized intravascular
coagulopathy (33). This is more common with limb and trunk involvement and is believed to be
related to stagnant blood. Thrombocytopenia and hypofibrinogenemia are less profound than in
KMS (in which platelets are often below 10,000 to 60,000), D-dimer, fibrin split product levels,
and prothrombin and possibly activated partial thromboplastin times are higher, and rather than
being confined to infancy, the onset is more typically in adolescence or adulthood and persists
during life to a varying degree (15,33). The coagulopathy predisposes to thrombotic and
bleeding episodes, can be improved with compression stockings and low molecular weight
heparin (unlike in KMS), and may worsen with embolization or surgery.
Imaging shows a soft tissue mass that slowly enhances (unlike lymphatic malformations),
possibly contains phleboliths, and possibly has associated bone or joint abnormalities (4,23,28)
(Fig. 32-4A to 32-4E). On ultrasound, the mass is compressible, hypoechoic, or heterogeneous
with anechoic channels in up to 50%, with low monophasic or no flow. Reflux can be seen in
dysplastic, varicose veins. While computed tomography (CT) may better depict bony effects,
phleboliths, and occasional fatty components in the hypodense or heterogeneous mass (34),
MRI is the best study (28,29,35, 36, 37). It will portray the extent (often greater than clinically
apparent), infiltrative or well-marginated characteristics, the relationship to other structures
such as nerves and bones, possibly the venous drainage, and the status of regional conducting
veins (MR venography may further help). Lesions are hypointense or isointense on T1-weighted
images and hyperintense on T2-weighted and inversion recovery sequences, with the latter
usually best demonstrating extent. Hemorrhage and thrombosis can give heterogeneity and
fluid-fluid levels. Septae and phleboliths will be hypointense.
Regional venography injecting a peripheral vein will generally not fill a VM due to its poor
connection with conducting veins but may be helpful for depicting dysplastic veins. Direct
puncture intralesional venography is performed with a 20- to 22-gauge needle or angiocath and
a short extension tube or with a butterfly needle and can be guided by ultrasound, CT, or MR
(38) (Fig. 32-4F to 32-4H). After blood return, contrast injection opacifies variably sized
cavities, with subsequent filling of normal or dysplastic draining veins. Separate, unfilled
compartments may exist. On occasion, VMs may consist of dysplastic veins with immediate
drainage. Arteriography is unnecessary for pure VMs, which may be nonvisualized, have a few
small spaces opacified on later images or stain more densely on capillary and venous phases.
Treatment of Venous Malformations

Treatment of VM is indicated for active symptoms, to prevent complications such as
hemarthrosis, and for cosmetic concerns (20,23,28). Supportive measures include compressive
stockings to reduce distension and stagnation and low-dose aspirin to reduce thrombosis.
Thrombotic episodes can be managed with elevation, nonsteroidal anti-inflammatory agents,
and warm compresses. Surgical resection is more successful for smaller, localized lesions and
is probably best done after initial sclerotherapy. Difficulties include hemorrhage, disfiguring or
functional effects from resection of surrounding tissue, and the propensity for recurrence.
Patients with VM-related coagulopathy should receive heparin. Tiny superficial skin lesions may
be treated with laser photocoagulation.
Many consider the preferred treatment of VM to be direct puncture sclerotherapy, the goal of
which is to cause endothelial destruction and subsequent fibrotic obliteration of the vascular
space. Sclerotherapy can be performed under moderate sedation, although some recommend
anesthesiology monitoring, especially when using alcohol and when treating lesions near critical
structures (26). Outpatient ultrasound-guided polidocanol foam sclerotherapy without
anesthesia has also been described (39). Patients generally receive steroids before and a
tapering dose for several days afterward to limit swelling, as well as nonsteroidal anti-
inflammatory agents. With alcohol and higher doses of detergent sclerosants, a sodium
bicarbonate intravenous infusion can be used to alkalinize the urine and help protect against
renal damage from hemoglobinuria.
FIGURE 32-4. Persistent, painful, mixed low-flow LVM in a 13-year-old right-handed girl
despite prior resection. A well-circumscribed, lobulated intramuscular hypodense mass on
CT scan contains a phlebolith (A). The mass has multiple, anechoic compressible spaces
on ultrasound, with no flow on Doppler interrogation (arrows) (B). On MRI, it is
hyperintense on fat-saturated T2-weighted imaging (C), isointense to muscle on T1-
weighted gradient recalled echo imaging before contrast, with small voids from phleboliths
(D) and regions of enhancement after contrast (E). The lesion infiltrates the region of the
radial nerve and a component is present within the olecranon. Direct puncture venogram
with a 21-gauge needle shows several phleboliths (F) and filling of a space with poor
communication to normal veins (G). After several injections of STS foam, puncture
venography of a remaining compartment of the malformation shows filling of tiny draining
veins (arrow) (H). Final appearance of the lesion after sclerotherapy on fluoroscopy (I) and
ultrasound (J), with echogenic shadowing foam evident on the latter. On follow-up, the
patient had marked symptomatic improvement and reduction in the size of the LVM on
MRI.
The volume of the lesion is determined by an initial direct venogram, stopping when normal
draining veins first fill (Fig. 32-4F to 32-4J). A similar volume of sclerosant is then injected,
displacing the contrast, and permitted to dwell for 5 to 15 minutes before repeating a contrast
injection. Alternatively, opacified sclerosant can be injected. Spread of the sclerosant into
draining veins should be avoided, particularly conducting veins, which can lead to deep vein
thrombosis or systemic complications. Tourniquets, direct manual or instrument compression,
and even coil embolization of a noncritical draining vein may be used to slow escape of the
sclerosant from the VM. Local extravasation should also be avoided. Often more than one
injection per needle puncture will be needed. Additional punctures are determined by identifying
residual patent portions of the VM by ultrasound or palpation for more superficial lesions. If
desired, a small amount of collagen may be injected upon needle removal to limit leakage of the
sclerosant. A compression bandage or stocking is often then placed, although the need for this
is debated and caution is advised in patients at risk for compartment syndrome. Whether to
admit the patient depends on local preferences, the degree of postprocedure pain, the agent
used (patients are generally watched for 24 hours after alcohol), and the risks. For example,
lesions near the airway may require the patient to remain intubated (26).
Sclerosants Used for Venous Malformations

Sclerosants commonly used for VMs include 95% or absolute (dehydrated) ethanol, detergent
agents, and Ethibloc. Intravascular alcohol is highly toxic to the intima, dehydrating and
denuding endothelial cells, causing protoplasmic precipitation, potentially inducing spasm, and
producing thrombosis by denaturing blood proteins (40, 41, 42). Its extensive obliteration of the
endothelium is believed to lead to greater success and permanence, preventing recanalization.
However, it also has a tendency toward more pain, swelling, and complications (26,43, 44, 45,
46, 47). Its proclivity to readily disperse can lead to perivascular tissue injury, including
peripheral nerves, skin, mucous membranes, and muscle. Systemic effects include of CNS
depression, nausea, headache, seizures, hyperthermia, hypoglycemia, hemolysis with
hemoglobinuria, rhabdomyolysis, tachycardia, hypertension, hypotension, cardiac dysrhythmias,
tachypnea, respiratory depression, hypoxemia, pulmonary vasospasm and hypertension (48),
and cardiopulmonary collapse. Some recommend using a pulmonary artery catheter to monitor
pressures, which may rise prior to cardiopulmonary collapse and be treated with intravascular
nitroglycerine (49). Alcohol as well as sodium tetradecyl sulfate (STS) has also been shown to
result in mild hemostatic abnormalities, which may be more significant in patients starting out
with a consumptive coagulopathy (50). Complications from alcohol appear related to the
amount used, with recommended maximum doses of no more than 0.5 to 1 mL/kg (45,47).
Ethanol can be made radiopaque by mixing 10 parts of it with 1 to 2 parts
of iodized oil, such as Ethiodol (Savage Laboratories, Melville, NY).
Commonly used detergent sclerosants include STS and polidocanol, while sodium morrhuate
and ethanolamine are less frequently employed. These agents cause intimal inflammation and
thrombus formation, with eventual replacement by connective tissue (51,52). While polidocanol
has been reported to have less allergic and inflammatory reactions (53), it is not commercially
available in the United States. Detergent sclerosants can be diluted to a lower concentration for
smaller-caliber vascular structures using saline or water-soluble or oily contrast if opacification
is desired. They may be injected as a liquid or a foam, which may be created by mixing the
agent with air or carbon dioxide at varying ratios up to 1:5. Foam has several advantages (54):
(a) instead of mixing with blood, foam displaces it, preventing dilution and providing more
thorough and prolonged intimal contact; (b) a small amount of the agent will provide a large
volume of foam, giving a lower total dose; (c) extravasated foam appears to be better tolerated
than extravasated liquid; and (d) echogenic foam is visible for ultrasound-guided procedures.
Detergent agents appear to have a better safety profile, although local and regional
complications still occur, predominantly skin ulceration (presumably from extravasation or
capillary reflux), pigmentation changes, and, rarely, peripheral nerve injury (39,44,55, 56, 57).
Central neurological effects have also been described in patients undergoing sclerotherapy for
varicose veins, especially when used as a foam, although serious events are extremely rare
(58). Allergic reactions have been described (55). Maximum recommended treatment volumes
per session for detergents are not certain, although as much as 30 mL of liquid STS and 40 mL
of foam have been used (44,54).
Ethibloc (Ethnor Laboratories/Ethicon, Norderstedt, Germany) is a viscous, radiopaque
alcoholic (60%) solution containing corn protein, sodium diatrizoate for radiopacity, propylene
glycol for sterility, and oleum papaveris for soft consistency that is not available in the United
States (59,60). The alcohol and corn protein produce inflammation, necrosis, thrombosis, and
eventual fibrosis, while its viscosity and solidification upon contact with blood limit migration.
While safer than pure alcohol, Ethibloc probably gives a more severe local reaction than
polidocanol or STS, and extrusion of the agent has been described (59,60).
Results of Venous Malformation Sclerotherapy

While rapid relief is seen in some patients after sclerotherapy, in others, the VM may become
more swollen and painful due to thrombosis and edema. This may persist for a few weeks and
then slowly recede, so a clinical response may not be seen for a couple of months. If
necessary, repeat treatments can be done every few months or longer.
Complications may occur in nearly 30% of patients, although most are minor and self-limited
(39,44,47,55, 56, 57,60). Local complications may be due to direct tissue injury, pressure from
local edema or compartment syndrome, or ischemia from reflux of the sclerosant into capillaries
or arterioles. While skin blistering may be seen in as many as 50% of patients, this is generally
considered a side effect. Skin ulceration with possible subsequent scarring has been noted in
up to 14%. Nerve injury is reported in up to 10%, often transient but occasionally permanent,
and mostly seen with alcohol. Muscle injury is less common (47). Hemolysis with
hemoglobinuria has been reported as high as 30% and 67%, also more common with alcohol. It
is usually benign when treated with a bicarbonate infusion (39,44,47). One series reported
deep venous thrombosis in 10%, with pulmonary embolism in 20% of these, but this has rarely
been noted by others (47). Infection is also uncommon, although 7.5% in one report (44).
While VMs are infrequently cured, symptomatic improvement can be achieved in most patients,
albeit often requiring several sessions and occasionally combined with surgery. Looking at
series using only a single agent, satisfactory results have been reported in 59% to 95% of
patients with alcohol (46,47,61,62), in 68% to 86% with liquid STS (56,57), in 87% to 100%
with polidocanol foam (39,63), and in 74% with Ethibloc (59). Smaller, more localized, and well-
defined lesions are generally found to have a more favorable outcome (59,62). Larger lesions
are more prone to recanalize and require more treatment sessions (39,55,60). Interestingly, the
symptomatic response is often greater than the imaging response, possibly due to decreased
distensibility and/or destruction of pain fibers (64). Ultrasound-guided endovenous laser ablation
of VM has also been described, with excellent symptomatic results in a more recent small
series (64).
LYMPHATIC MALFORMATIONS
Lymphatic malformations (LMs) may be microcystic (older terms, lymphangioma and
cavernous lymphangioma), macrocystic (cystic hygroma), or combined (10). Microcystic LMs
have multiple tiny cysts smaller than 2 mL in a solid matrix, while macrocystic lesions vary,
some spaces being quite large (65). The cysts contain straw-colored, protein-rich fluid and the
variably thick walls have abnormally formed muscular elements (20). Communications with
adjacent veins may be present, particularly for macrocystic lesions (23), although a primary
LVM may also explain this. No etiology is known, although in utero LMs may be associated with
chromosomal abnormalities such as Turner's syndrome, Noonan's syndrome, multiple pterygium
syndrome, and trisomies, and may result in hydrops fetalis (4,66).
LMs are usually found to be the second most common type of vascular malformation, after
VMs (10), although, when additionally considering dysplasias of major lymphatic channels
(truncular lesions), Lee et al. (17) found LMs to exceed VMs. Truncular LMs consist of aplasia,
obstruction, or non-functional hyperplasia of major conducting channels in the extremities, more
often the lower limb, with primary lymphedema (67,68).
The classic LM generally presents within the first 2 years of life and the majority are in the face
and neck (70% to 80%), followed by the axilla and chest (20%), the superior mediastinum,
mesentery, retroperitoneum, pelvis and buttocks, and lower extremities (4). A noncompressible
soft tissue mass will often be present with macrocystic LMs (in contrast to the compressible
VM), usually with normal overlying skin or a bluish hue, and diffuse soft tissue thickening can
occur with microcystic lesions (10,13,23,66). Microcystic dermal involvement can produce tiny
vesicles, which can leak fluid and become red from bleeding. Skin changes can also be related
to a coexistent CM. LMs can have bony and soft tissue overgrowth. Significant disfigurement
and impairment of normal function can occur, including compromise of the airway, speech,
swallowing, proptosis, and motion. Acute exacerbations, with rapid enlargement and possibly
ecchymosis, erythema, fever, and tenderness, often indicate hemorrhage and/or infection.
Intrathoracic and intra-abdominal involvement can result in chylothorax and chylous ascites.
Gorham-Stout syndrome (disappearing, vanishing, or phantom bone disease) consists of
osteolysis from diffuse soft tissue and skeletal LM (20).
MRI is the best imaging modality, particularly for deeper LMs, optimally depicting the extent
and status of surrounding structures (4,13,23,35,69). Macrocystic lesions are typically
hypointense on T1-weighted images and hyperintense on T2-weighted images, but fluid-fluid
layers of varying signal intensity may be seen after infection or hemorrhage. Rim and septae
may or may not enhance, but internal enhancement is
not typical, unlike VMs (Fig. 32-4). Adjacent veins may be enlarged. Microcystic lesions are
diffusely infiltrative solid masses of intermediate signal on T1-weighted images and high signal
on T2-weighted ones, with no enhancement. Surrounding lymphedema may be evident.
Ultrasound of macrocystic LMs demonstrates noncompressible cystic spaces with thin walls
and possibly internal septations and mobile echogenic debris from prior hemorrhage or
infection. The numerous tiny cysts of microcystic LMs may be below the resolution of
ultrasound, giving just a largely avascular, echogenic solid lesion. LMs are of lower density than
muscle on CT, which also depicts bone changes well.
Treatment of Lymphatic Malformations

Treatment is indicated for cosmesis, for functional improvement, and to avoid the consequences
of hemorrhage and infection. Antibiotics are indicated when infection or hemorrhage has
occurred. Macrocystic lesions are often well managed by sclerotherapy and also excision, if the
anatomy is appropriate for the latter (7,70). Combinations of sclerotherapy and surgery may be
needed for more complex and persistent or recurrent lesions. Microcystic LMs are generally
considered more difficult to manage, with surgery employed if absolutely necessary, although
recent results with sclerotherapy have been encouraging (70). Surgery is complicated by
difficulty in achieving complete resection, in part due to the frequent involvement of critical
structures (71, 72, 73). Local complications of lymphorrhea, edema, wound infection, and nerve
injury are not uncommon, as are recurrences. In addition to resection, supportive operations
such as tracheostomy and reconstructive procedures may be necessary.
Ultrasound guidance is useful for guiding access for sclerotherapy (70,74). A variety of different
needles, angiocatheters, and even angiographic type catheters can be used. After fluid is
aspirated, an appropriate volume of sclerosant for the cavity is instilled. A test injection of
contrast is occasionally administered. The sclerosant is usually left in place and the access
removed while applying pressure. If a catheter is to be left in place, it can be closed for up to
several hours and then reopened to drainage (75). Repeated treatments are performed as
needed, as soon as 1 day to, more typically, several weeks to months. Some place a pressure
dressing afterward, if feasible (74), and others recommend prophylactic antibiotics for 10 days
(26).
Commonly used sclerosants for LMs are bleomycin, OK-432, doxycycline, and ethanol,
although other agents include STS, Ethibloc, and hypertonic glucose (7,23,65,70, 71, 72,74,
75, 76, 77, 78). Bleomycin is a cytotoxic antitumor antibiotic that inhibits DNA synthesis and
also has an irritating, sclerosing effect on endothelium (65,74). OK-432 (Picibanil, Chugai
Pharmaceutical Co., Tokyo) is a lyophilized mixture of attenuated group A Streptococcus
pyogenes incubated with benzylpenicillin that induces an inflammatory response and
subsequent sclerosis (65,78). It is not available in the United States. Doxycycline is a
tetracycline-class antibiotic whose injurious effect on endothelial cells is not understood.
Results for macrocystic LMs are typically successful, with rates of >60% to 80%, while for
microcystic lesions the rates are often no more than 40% to 50% (65,68,72,74,76, 77, 78, 79).
However, using four agents over time, ethanol, STS, OK-432, and doxycycline, Alomari et al.
(70) found subjective response rates of 100% for macrocystic, 86% for microcystic, and 43%
for combined LMs. The complication rate in this series was 22%. Local complications are most
common, such as skin blistering, ulceration, and swelling, with pain, although cellulitis,
intralesional hemorrhage, and scarring may also occur. More serious and permanent
complications appear more common with alcohol, including extralesional injury such as nerves.
Systemic reactions include fever, vomiting, and rarely, reported with bleomycin, hair loss.
Pulmonary toxicity from bleomycin has not been reported (65,72,74). The most frequent
complication with Ethibloc is skin breakdown with leakage (79).
PRIMARY LYMPHEDEMA
Primary lymphedema of the limbs may present at birth (Milroy disease), puberty (Meige
disease), or, less commonly, adulthood (67). These may be inherited, with linkages to VEGFR-
3 found for Milroy disease and FOXC2 for Meige disease, which also includes distichiasis
(double rows of eyelashes), ptosis, cleft palate, yellow nails, and congenital heart disease.
Pitting edema is initially found but this will progress to nonpitting edema as excess interstitial
protein leads to fibroblast proliferation and organization, along with skin and subcutaneous
tissue overgrowth (80). Infections are frequent while degeneration to lymphangiosarcoma is
rare (67). If the diagnosis is not clinically certain, lymphoscintigraphy may be helpful. Studies to
assess for coexistent venous disease that may be treatable should be considered.
The mainstay of treatment for primary lymphedema is decongestive lymphatic therapy (68,80).
This consists of elastic compression stockings, daily manual lymphatic drainage (a specific type
of massage), and meticulous skin care. On occasion, intermittent pneumatic compression may
be added. Lymphaticovenous anastomoses, free lymph node transplantation, and resection of
the overgrown soft tissue may play a role in intractable cases (68). Primary visceral
lymphedema with effusions, ascites, mass effect, protein-losing enteropathy, and intestinal
bleeding and are more problematic to manage.
ARTERIOVENOUS AND ARTERIAL MALFORMATIONS

Arteriovenous malformations and arterial malformations (AMs) are high-flow lesions. The
former consist of direct AV shunts, lacking an intervening capillary bed, and may be divided into
complex lesions, with multiple, plexiform communicating AV channels (the nidus) and often
multiple feeding arteries and draining veins, or simple ones with a solitary channel, referred to
as arteriovenous fistula (AVF) (23). Congenital AVF should be distinguished from the more
common acquired type, which generally results from trauma (including iatrogenic) and, less
commonly, rupture of an aneurysm into a vein or erosion of adjacent vessels by infection or
tumor. This distinction may be difficult, and with chronicity, acquired lesions can appear like
complex AVMs. Persistent embryonal arteries (such as persistent sciatic artery) and aplastic
and dysplastic arteries, possibly with aneurysmal formation, represent pure AMs, without
shunting into veins (81).
Most AVMs are sporadic, the major exception being hereditary hemorrhagic telangiectasia, a
heterogeneous, heterozygous autosomal dominant, multisystem disorder that is more
thoroughly discussed in the chapter on pulmonary AVM. While believed to be present at birth,
AVMs are often not recognized until childhood or later. The growth pattern of AVMs is the same
as with other vascular malformations, although more aggressive growth is of particular concern
after unsuccessful surgical resection or proximal arterial ligation or embolization (82). The
extent varies from a more localized lesion to diffuse tissue involvement. The most common
locations for AVM are intracranial followed by the extracranial head and neck, extremities,
trunk, and visceral sites (10,17,82).
With superficial AVMs, a warm, pulsatile, erythematous mass may be evident with a thrill or
bruit and a continuous
murmur. Prominent, possibly pulsatile draining veins may be present, as well as other evidence
of venous hypertension, such as skin changes, edema, hyperpigmentation, and venous
ulceration. Regional arterial steal can result in ischemia, with pain, arterial ulceration, bleeding,
and gangrene. Soft tissue and bony growth disturbances may occur from alterations in blood
flow and/or coexistent anomalies. With visceral malformations, splanchnic steal can result in
mesenteric ischemia. Intestinal and renal lesions can give bleeding (83), while the most
common manifestations of symptomatic liver AVMs, generally seen in patients with hereditary
hemorrhagic telangiectasia, are ischemic biliary track disease, portal hypertension, and/or high
output failure (84). Pelvic AVMs may give menometrorrhagia, infertility, hematuria, and pain.
True uterine AVMs should be distinguished from more common acquired AV shunting lesions,
which have been reported in the setting of miscarriage, termination, curettage, Cesarean
section, infection, carcinoma, trophoblastic disease, myomata, and use of diethylstilbestrol
(85). While uncommon, left-to-right shunting from any AVM may be sufficient to give high output
heart failure.
Plain radiographs may show bone changes such as erosion and osteopenia but are often
unrevealing. Ultrasound shows enlarged vessels with no well-defined tissue mass (4). Doppler
analysis confirms the diagnosis, showing high systolic and diastolic (low impedance) flow in
feeding arteries as well as draining veins, with the latter also being pulsatile (arterialization)
(82,86), and doppler studies can show the effects of treatment (42,49). CT depicts a rapidly,
strongly enhancing lesion with rapid washout and multiple enlarged feeding and draining
vessels. CT angiography may be helpful in depicting angioarchitecture. As with low-flow
vascular malformations, MRI is the most valuable noninvasive study, depicting the extent within
tissues and the relationship to normal structures (13,29,35, 36, 37). Unlike slow-flow lesions,
AVMs show signal voids from the numerous fast flowing vessels on both T1- and T2-weighted
sequences, except for hyperintense hemorrhagic or thrombotic foci (Fig. 32-5A). The lack of
any nonvascular soft tissue mass distinguishes these from hypervascular tumors, although
aggressive lesions such as rhabdomyosarcoma, angiosarcoma, and hemangiopericytoma may
occasionally be confusing. Like CT angiography, MRA will demonstrate angioarchitecture, but
conventional catheter angiography is better.
FIGURE 32-5. A 36-year-old man with a painful left upper extremity from a diffuse complex
AVM. T1-weighted MRI shows extensive infiltration with numerous voids from high-flow
vessels (A). Mid (B) and late (C) arterial phase brachial arteriography confirmed dense
involvement, predominantly along the radial aspect of the forearm and hand, with enlarged
radial and interosseous arteries and numerous small arteriovenous connections rapidly
filling the cephalic vein (arrows). Radial artery branches are better seen during selective
angiography with a blood pressure cuff inflated (D).
Angiography is generally indicated only when therapy is planned. It is the best study for
showing the origins of enlarged, tortuous arteries, the characteristics of the nidus, and the early
flow into enlarged draining veins. The nidus may be a complex multichanneled one with various-
sized AV connections or the single large connection of a congenital AVF. Complex lesions can
be focal (Fig. 32-6A) or diffuse (Fig. 32-5B and 32-5C), with extensive supply from all regional
arteries. Images are acquired rapidly and selective vessels injections are helpful, as may be
slowing flow with an occlusion balloon or external cuff (Fig. 32-5D). With larger AVMs, a
simultaneous right heart catheterization will further characterize deleterious hemodynamic
effects, including elevated cardiac index and elevated right chamber, pulmonary artery, and
pulmonary artery wedge pressures. Evaluation by cardiology may be appropriate to help
manage high-output heart failure.
FIGURE 32-6. A 56-year-old man with pain and multiple episodes of bleeding from
chronically enlarged right third and fourth toes. Frontal angiography showed a localized
complex AVM principally supplied by digital arteries off the third and fourth metatarsal
arteries derived from the arch through the dorsalis pedis artery (arrow) (A). Amputation
was planned but preoperative embolization to help with vascular control was indicated. The
digital branch of the fourth toe supplying this region of the AVM was first selected with a
microcatheter (B) and embolized with n-butyl cyanoacrylate, followed by the digital branch
to the third toe. The opacified glue is well visualized (C) and final angiography (D) shows
minimal residual supply remaining from a branch of the second metatarsal artery (arrow).
The amputation was uneventful and the patient was cured.
FIGURE 32-7. A 75-year-old woman with severe heart failure and a large right renal
arteriovenous fistula, believed to be congenital in origin (A). This was embolized with wire
coils after first placing a curled removable core wire for a large scaffold to prevent
paradoxical embolization (B). The patient's cardiac output decreased from 8.2 to 5.5
liters/minute and she showed marked symptomatic improvement.
Treatment of Arteriovenous Malformations

The decision to treat an AVM aggressively rests on its complexity and the degree of symptoms.
The more complex, extensive, and infiltrative the lesion, the more significant the symptoms
should be before embarking on invasive therapy. Also, improper therapy of an AVM can
eventually result in worse symptoms and increase the difficulty of subsequent treatments. Tan
et al. (87) listed the following criteria for treatment: (i) hemorrhage, (ii) disabling pain requiring
regular use of analgesia, (iii) functional impairment secondary to swelling or pain, (iv) ulceration,
and (v) high-output cardiac failure. Cosmetic deformity was considered a relative indication.
Patients not meeting these criteria were treated conservatively, with advice on limb care,
compression garments, and simple oral analgesia as needed, with only 1 of 11 patients having
mild symptom progression over a mean follow-up of 3.4 years. Due to their complexity and the
frequent need for multiple therapeutic modalities, a multidisciplinary team is especially helpful
for managing AVMs. The limited chance of complete cure and the likely need for repeated
procedures with complex AVMs should be thoroughly discussed with the patient.
The goal of therapy is to occlude or remove the nidus. Proximal vessel ligation (including
skeletization of all afferent vessels) or embolization should be avoided, as this results in
temporary improvement at best. Subsequent collateral vessels supplying the AVM make
reaching the nidus more difficult (88,89). Currently, embolization is generally considered the
primary therapeutic modality for AVMs, with the possible exception of small, localized lesions;
however, even with these, preoperative embolization offers the advantage of better vascular
control (42). Embolization of the nidus is most often achieved through a transarterial approach
but direct nidal or perinidal (feeding arteries and draining veins) punctures and retrograde
transvenous approaches are sometimes employed (49,90, 91, 92). The latter two methods are
particularly helpful for arterially inaccessible lesions and those with a single outflow vein that
can be tracked back to the nidus.
Congenital AVFs are often the most straightforward lesions to manage and cure, although the
sometimes enormous size of the connection can present challenges. These are most commonly
seen in the lungs and kidneys. Embolization is best accomplished with mechanical agents
placed distally in the feeding artery. Coil emboli are generally used, occasionally combined with
a manually coiled removable coil wire as the initial large retaining framework (Fig. 32-7).
Complex AVMs are generally best treated with liquid embolic agents, with the prevalent ones
being the sclerosant ethanol and cyanoacrylic adhesives (glues) (49,87,93). The role of the
nonadhesive liquid embolic agent Onyx (Micro Therapeutics, Inc., Irvine, CA) for peripheral
AVMs is not yet clear (94). Particulates such as polyvinyl alcohol particles have a more limited
role due to difficulties in judging the correct particle size to lodge in the often variably sized AV
shunts without passing through or occluding too proximally and concerns over recanalization
even with plastic agents (95,96). Coil emboli may be used for occluding or slowing flow through
a dilated, dominant outflow vein, often combined with a liquid agent (49). Occasionally, coils
may also be used for aneurysmal arterial components (87) or for slowing flow prior to use of a
liquid agent, being careful to avoid proximal occlusion of an AV connection.
The ability of alcohol to destroy the intima and obliterate the vessel along with its ease of
delivery through even smalllumen catheters makes it a highly attractive agent. It is strongly
favored by some who feel that it has the greatest potential to achieve permanent nidal
obliteration (42,49). However, the toxicity of this agent mandates extreme caution and risks
more serious complications, including injury to adjacent normal tissues (especially nerves,
mucosal surfaces, and skin) and systemic effects.
The current cyanoacrylate used for embolization is n-butyl cyanoacrylate (97). Polymerization
occurs upon exposure to anions, as present in blood. As electrolytic solutions such as
saline will also cause polymerization, a separate table and clean gloves should be used to
prepare the glue, and eye protection is recommended. Polycarbonate syringes should be
avoided, as this plastic is degraded by cyanoacrylates. The glue can be rendered radiopaque
by adding tantalum powder and/or iodized oil. The latter is typically added at ratios of 1 part
glue to 1-6 parts oil, which also slows the polymerization time. A nonionic solution such as
dextrose in water is used for catheter flushes before injecting glue, and afterward, if the
treatment catheter is not immediately removed with aspiration. If left in place, the catheter
should be retracted while administering the postinjection flush to avoid gluing the catheter tip in
place.
Their low viscosity makes cyanoacrylates easy to inject through narrow-lumen catheters. When
injecting into an AVM, the goal is to create a cast of the nidus being fed by the relevant vessel.
As it polymerizes in vivo, n-butyl cyanoacrylate will incorporate thrombosed blood elements, so
the volume of glue needed is usually less than the estimated vascular territory. Glue will also
cause an acute inflammatory reaction in the vessel wall and surrounding tissues that
progresses to a chronic and granulomatous process over ~1 month. The occlusion caused by
glue is not necessarily permanent, with recanalization more likely if embolization is incomplete
(98). Advantages of glue are its relative lack of cytotoxicity and low complication rate (87,93).
Embolization of an AVM may be performed under moderate sedation or general anesthesia
depending on the degree of pain expected and on the risks, especially systemic effects if
ethanol is used. Once again, a pulmonary artery catheter may be useful for monitoring patients
receiving larger volumes of alcohol. Corticosteroids given before and as a tapering dose
afterward can help limit local edema, and postprocedure pain can be treated with nonsteroidal
and narcotic analgesics. Nausea, vomiting, and fever may also occur. A sodium bicarbonate
intravenous infusion may help protect against renal damage when alcohol is used.
Transarterial embolization with liquid agents is best performed through a coaxial microcatheter
placed in a feeding artery as close to the nidus as possible and beyond any branches to normal
tissue (Fig. 32-6). Introducing the catheter reasonably distally in the parent artery provides
support, enables rapid exchanges for new microcatheters, and permits relatively selective
contrast injections, which may be made through the microcatheter in place if a nontapered
guide is used. Contrast is carefully injected through the microcatheter, noting the volume
needed to fill the nidus until the draining vein is seen. Slowing flow with an occlusion balloon,
applying external pressure (such as a cuff about an extremity), or wedging the microcatheter in
a small feeding artery may help in this process and reduce the risk of paradoxical embolization.
With very peripheral lesions, nontarget digital arteries may be protected by placing elastic
bands about the digits. The ethanol or glue is then injected, being sure to immediately retract or
remove the catheter if glue is used. Several injections are often needed to achieve complete
regional embolization. Generally, it is recommended to treat only a limited territory at one time,
meaning moderate-sized and larger AVMs will require multiple sessions.
Direct nidal or peri-nidal punctures can be performed with 18- to 22-gauge needles or
angiocaths followed by contrast injections and administration of the desired liquid embolic.
Transvenous approaches to the nidus can also be used, possibly with coil embolization of an
outflow vein, an arterial occlusion balloon, or external compression to reduce the flow.
Transarterial, direct, and transvenous approaches are often combined.
Localized complex AVMs may be managed by embolization, surgery, or, often, a combination of
these (Fig. 32-6). Surgical options consist of resection of the nidus (generally after initial
embolization), which may include a relatively minor amputation such as of a digit and/or ancillary
procedures such as revascularization and skin grafting for ulcers. Marked symptomatic
improvement is often achieved in these patients and, occasionally, cure (17,49,87,93,99).
Diffuse, infiltrating complex AVMs are more problematic (Fig. 32-5). While embolization is the
first line of therapy, cure is rarely achieved. Nevertheless, palliation is often possible,
concentrating on treatment of more symptomatic regions. Surgical extirpation of the AVM alone
is not feasible, although lesions confined to an organ such as the uterus may be cured with
resection of the organ. Diffuse extremity lesions are at higher risk for major amputation,
especially those involving all major arterial trunks (93,99,100).
Complications after embolization appear to be more common and more serious when using
ethanol, with overall rates >50% (17,49). Minor events such as transient skin blisters or
necrosis and transient peripheral nerve injury predominate after alcohol embolization, but major
complications occur in ~10%. The overall rate of complications with glue embolization is no
more than 10%, with skin injuries almost never seen, transient nerve injury rare, and significant
nontarget and paradoxical pulmonary embolization uncommon (17,87,93,101). Gluing of the
catheter tip in place has not been reported in the few larger series of peripheral AVMs.
Precise results of AVM embolization are difficult to specify, as reports often consist of small
numbers of patients and may mix lesions in different locations, different architectural types of
lesions, and different embolization methods. Looking at larger series, Do et al. (49) reported a
cure rate of 40% using alcohol and improvement in another 28% of AVMs in a variety of
locations. In two series of extremity AVMs treated with glue, Tan et al. (87) reported cure or
improvement in 62% while in our own experience (93) we achieved this in 75%, some also
undergoing surgery, while the other 25% eventually went on to amputation even if temporary
improvement occurred. However, our series excluded four previously reported patients with
diffuse upper extremity AVMs, of whom two eventually had amputations (100). Lee et al. (17)
achieved cure in all 16 localized AVMs treated with embolization and excision, while excellent
clinical results were achieved in 78% of infiltrating lesions treated with embolization.
Improvement in bleeding and successful pregnancies have been reported after treatment of
uterine AVMs, although hysterectomy is ultimately required in some patients (102). Jacobowitz
et al. (101) had an 83% improvement rate in a series of pelvic malformations that were
predominantly AVMs and noted that pelvic AVMs in males tended to be simpler and more
readily managed with fewer embolization sessions. Takebayashi et al. (103) were able to
control hematuria in nearly all patients with renal AVMs treated with alcohol, while all of the
smaller number of patients treated only with particulates had recurrences and were
subsequently treated with alcohol. Liver AVMs appear most commonly in patients with
hereditary hemorrhagic telangiectasia and, when symptomatic, can be difficult to manage.
Embolization risk is significant, even fatal, and so it is not recommended (104,105). Supportive
therapy and transplantation should be employed (84,105).
COMBINED SLOW-FLOW VASCULAR MALFORMATIONS

Excluding LVMs, the prototype for mixed low-flow vascular malformations is Klippel-Trenaunay
syndrome (KTS), which combines abnormalities of capillaries, veins, and lymphatics in various
degrees, along with regional tissue overgrowth (23,106). Sturge-Weber syndrome, described
earlier, is primarily a CM; opinions differ regarding whether it can occur mixed with other
vascular components (10,106).
KTS affects both sexes equally and has no identified genetic basis (106,107). It usually involves
a single extremity,
most commonly a lower one, possibly with extension into the adjacent buttock, less commonly
an upper extremity or combination of lower and upper limbs, and is rarely isolated to the pelvis,
abdomen, thorax, or head and neck. The classic triad is a port-wine stain CM birthmark,
varicose veins evident in childhood, and bony and soft tissue hypertrophy, generally with limb
elongation (Fig. 32-2). Some feel the diagnosis can be made with only two elements present
(107). Dilated, valveless embryonic venous channels are common, epitomized by a laterally
located tortuous vein arising from veins in the dorsum of the foot and ascending all or most of
the length of the lower limb before ending in a deep vein (Fig. 32-8). The normal conducting
deep veins may be hypoplastic, absent, or dilated and incompetent, further contributing to
superficial varices. Similarly, lymphatic channels may be absent, hypoplastic, and reduced in
number, even in the absence of overt lymphedema or lymphatic vesicles. Occasionally, small,
nonsignificant AVFs may also be present but large ones are not seen. In addition to bony
overgrowth, other skeletal anomalies are occasionally found, such as congenital hip dislocation
and syndactyly.
FIGURE 32-8. Teenage girl with a painful right lower extremity who has mild KTS.
Inversion recovery MRI shows the dysplastic lateral embryonic vein on coronal images of
the leg and knee (solid straight arrows). Transverse images show it emptying into the deep
venous system in the midthigh (open arrows) and through a horizontal branch to the great
saphenous vein (curved arrow). The deep venous system was intact. The dysplastic vein
was treated with endovenous laser ablation with significant symptomatic improvement.
In addition to cosmetic concerns, patients with KTS may have pain, tenderness, bleeding,
superficial thrombophlebitis, infection, ulceration, and other sequelae of venous hypertension,
as well as problems related to leg length discrepancy (23,107). Hematochezia, hematuria,
vaginal and vulvar hemorrhage, and esophageal variceal bleeding may occur due to either
primary involvement of these regions or collateral flow through them as can occur from iliac and
portal vein anomalies. The extensive low -flow malformation may occasionally result in a
localized intravascular coagulopathy (106).
Plain radiographs may show the skeletal abnormalities, soft tissue overgrowth, and phleboliths
in VMs (23,108). Ultrasound is particularly useful for assessing the morphological and functional
(competence) status of the superficial and deep venous systems, as well as refluxing
perforating veins (13). MRI will demonstrate the extent of the venous malformation well and,
with MRV, can help assess the status of the conducting deep and superficial veins. Given the
information derived from ultrasound and MRI, contrast venography is rarely needed, although
direct puncture venography may be performed prior to treatment. Given the absence of
significant AVFs, arteriography has no role.
Conservative management of KTS is the standard, with graduated compression stockings and
limb elevation as well as
antibiotics and other appropriate measures for local complications. If significant lymphedema is
present, more aggressive decongestive therapy should be used. Obliteration of superficial
varices and more complex venous malformations by resection, endoluminal ablative techniques,
and/or sclerotherapy should be done only if these have been determined not to be essential
outflow channels in the setting of inadequate deep pathways (Fig. 32-8). Otherwise, new and
worse varices and edema may result. Limb shortening procedures may be necessary in the
affected lower extremity to prevent gait disturbances and scoliosis. Soft tissue debulking is
occasionally performed. Laser therapy may be tried for the superficial CM, although the
efficacy appears limited (109).
COMBINED VASCULAR MALFORMATIONS WITH HIGH FLOW

Parkes Weber syndrome consists of mixed capillary, venous, and arterial malformations and
should be distinguished from the more common KTS (23,106,107,109). Patients will have soft
tissue and bony overgrowth of an extremity, with a port-wine stain that is often more diffuse
and pinker than in KTS, venous abnormalities, and also manifestations of significant AV shunting
regional hyperthermia, bruit, thrill, and even heart failure. The physical and imaging
evaluations are similar to KTS, with the presence of significant AVFs making the distinction.
These may be evident on ultrasound and MR angiography, but arteriography may be needed
(13,23,110). Management is also similar to that of KTS except for the possibility of embolizing
the AVMs. Patients with Parkes Weber syndrome are more likely to suffer serious
complications from their disease than those with KTS (109).
Other rare syndromes that can have combined types of vascular malformations are Proteus
syndrome (111), Cobb syndrome (112), and an inherited syndrome related to RASA1 mutations
(113).
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Pulmonary Arteriovenous Malformation
Chapter 33
Pulmonary Arteriovenous Malformation
Bob White
Jeff Pollak
EPIDEMIOLOGY AND ETIOLOGY

Pulmonary arteriovenous malformation (PAVM) is a high-flow, low-pressure fistula, connecting a
branch pulmonary artery to a branch pulmonary vein. At the point where the artery and vein
connect, there are no capillaries but instead there is a thin-walled aneurysmal sac (1). Left
untreated, PAVM is an important cause of morbidity and/or mortality in about one half of
affected patients. Results of several meta-analyses suggest that 50% of patients will develop
brain abscess and/or stroke due to paradoxical embolus or lung hemorrhage (hemoptysis or
hemothorax) secondary to rupture of the aneurysmal sac (2,3).
The majority of patients with PAVM will have an underlying genetic condition, known as
hereditary hemorrhagic telangiectasia (HHT), formerly known by the eponym Osler-Weber-
Rendu syndrome. (4) This autosomal dominant disorder can be extremely subtle and is often
overlooked by physicians caring for a patient in crisis due to a stroke, brain abscess, or lung
hemorrhage.
The most prevalent symptom experienced by patients with HHT is epistaxis, occurring as
frequently as several times daily or as infrequently as once every other month. Five to 10% of
patients with HHT will never have a nosebleed. Since nosebleeds are the rule in these families
they often will not voluntarily describe them since they have accepted them as part of life, and a
history of epistaxis must be sought after in the individual patient. In adults bright cherry red
spots called telangiectases are found on close inspection of the lips, tongue, palate,
conjunctiva, nose, ears, and hands. These telangiectases blanch with pressure, unlike the
cherry angiomata so common on the chest of aging patients (4).
The constellation of a first-degree relative with HHT, a patient with epistaxis, and physical
findings of telangiectases establishes the clinical diagnosis (5). PAVM and liver AVM are
surrogates for one of the above clinical findings, and any three of the four criteria establish the
diagnosis (5,6). Clinical DNA testing has been available since 2004 in Canada and the United
States and longer in Europe. Four different genotypes are now recognized (4,7,8). HHT is
thought to affect about 200 individuals/1 million population and has no ethnic predisposition (4,9,
10, 11). If one pools all the phenotypes of the four different genotypes together, about one third
of patients with HHT will have PAVM.
CLINICAL AND LABORATORY FINDINGS
There are no specific laboratory findings in patients with PAVM. If patients are severely
hypoxemic due to right-to-left shunting through the PAVM, they may have polycythemia but
most will have iron deficiency anemia because of recurrent epistaxis, and in women repeated
epistaxis and menstruation lead to chronic iron depletion. In patients with liver malformations,
there may be minimal elevation in transaminases and or alkaline phosphatase. Patients with
more than one PAVM may have hypoxemia on room air, and if it is severe enough, the pulse
oximetry will be consistently below the normal values of 97% to 100%. A widened pulse
pressure is common in patients with severe anemia and large liver AVM due to increased
cardiac output.
Genetic testing is now widely available and has proven to be very valuable for large families, to
detect presymptomatic patients who are candidates for screening and treatment of
asymptomatic brain and lung AVMs. Treatment of presymptomatic patients with brain and lung
AVM is favored as long as the teams treating these patients are experienced in managing HHT
and the patients have received genetic consultation.
Role of Imaging Prior to Treatment

Imaging plays an important role before and after treatment of PAVM and also provides
guidelines regarding which patients should receive treatment (12, 13, 14, 15). Contrast
echocardiography is the first line of testing for PAVM at our center, following the well-conducted
studies by earlier Danish and Canadian workers (16,17) (Fig. 33-1). The basis of this test is
transthoracic echocardiography using the apex four-chamber view during the injection of
agitated saline intravenously. Saline is agitated by rapid exchange back and forth through a
three-way stopcock and then injected into an antecubital vein. Microbubbles (microcavitations)
appear in the right atrium and right ventricle and are filtered by an intact pulmonary capillary
circulation. When PAVM are present, the microcavitations appear in the left atrium after three to
five cardiac cycles, indicating an extracardiac right-to-left shunt. Caution should be exercised
not to confuse microbubbles in the left atrium from a PAVM with those due to a patent forman
ovale, which is present in 10% of the population. Sometimes they are difficult to distinguish from
one another, and this is one of the indications for further imaging. A complete history and
physical will in most instances point the way to the correct diagnosis of PAVM rather than
foramen ovale.
Sometimes, reviewing a prior chest radiograph will establish the diagnosis of a PAVM. An
enlarged artery and vein coursing to and from a peripheral mass (aneurysmal sac) are noted in
60%-70% of patients. Unfortunately, a chest radiograph is neither sensitive nor specific when
trying to phenotype a family with HHT. (18) When patients with known PAVM and patients with
other diagnoses were shown to chest radiologists
and pulmonologists, the resulting sensitivity/specificity was approximately 70% (18).
FIGURE 33-1. Current Yale HHT Center algorithm for diagnosis, treatment, and follow-up
of patients with pulmonary arteriovenous malformation.
Noncontrast computed tomography (CT) was advocated by the Remys in 1992 and 1994 as an
easy and straight-forward way to assess patients for PAVM and also to assess the anatomical
results following embolotherapy (14,19). A rapid diagnosis of PAVM may be obtained by
multidetector CT. An ongoing debate that is not settled is the need for use of contrast media
during the evaluation of these patients by CT angiography. While we have recently published
our outcomes using noncontrast CT for follow-up of patients undergoing embolotherapy for
PAVM, many of our colleagues prefer contrast CT studies (15). This reflects general
unfamiliarity with the literature about CT of PAVM and dependence of most radiologists on
contrast CT for most conditions. Our studies have clearly demonstrated that without contrast
media we can accurately determine the diameter of the artery supplying the PAVM as well as
the involution of the aneurysmal sac following successful embolotherapy (15). Our reluctance to
employ intravenous injections is because patients with PAVM are particularly sensitive to
inadvertent air injected at the time of starting an IV, and contrast CT can potentially cause air
emboli with symptoms. It is true that most sophisticated imaging centers will be careful to avoid
intravenous air but events still happen. Suffice it to say that studies with and without contrast
media have not been done in a fashion that would allow us to determine the value added by
using contrast media.
Spectacular images of PAVM have also been reported using magnetic resonance (MR)
angiography (20, 21, 22). As with CT, we see little reason to use MR angiography with
intravenous gadolinium for diagnosis or follow-up after treatment of PAVM. Again, as with
studies using contrast for CT, it is not clear that MRA with gadolinium will offer value added
information. In addition, contrast echocardiography does pick up PAVMs that are small and may
be missed by noncontrast CT. While such patients do not appear to be at risk for paradoxical
embolus and stroke or rupture of a small PAVM, they do appear to be at risk for brain abscess
or other infections. In patients with small PAVMs, prophylactic antibiotics before dental cleaning
or other invasive exams that potentially introduce bacteria should be administered.
Physiologic Studies and Shunt Measurement Using 100%

Oxygen or Radionuclides
The literature is replete with studies documenting the ability to quantify the magnitude of the
right-to-left shunt and the diminution in shunting after embolotherapy (23, 24, 25). In fact it was
our standard approach, along with noncontrast CT, at our HHT center until the early 2000s.
Now we prefer echocardiography and baseline supine and erect pulse oximetry in room air
(normal values 97%) coupled with an anatomical study such as noncontrast CT to assess
patients before and after embolotherapy of PAVM. In some instances, when there is a
multiplicity of PAVMs or they are extremely large, a follow-up outpatient pulmonary angiogram
is useful to prove successful permanent occlusion of the PAVM. Similarly, in patients with
markedly reduced oxygenation such as occurs in the 5% of patients with diffuse PAVMs,
pulmonary angiography may be a better way to assess them, coupled with exercise testing
using defined workloads and pulse oximetry (26).
Indications and Patient Selection

Since 1985, it has been recognized that patients with PAVM and a feeding artery 3 mm in
diameter are susceptible to paradoxical embolus and TIA or stroke (27). This is a threshold size
for paradoxical embolus of bland thrombus but of course much smaller PAVMs are associated
with brain abscess, and much larger PAVMs with pulmonary hemorrhage. In general it is our
goal of therapy to occlude all PAVM with arteries 3 mm and to follow closely all patients with
treated PAVMs as well as those with small PAVMs The 3-mm-diameter measurement is
performed from noncontrast CT or pulmonary angiography and is at the site where the artery is
of uniform diameter, preferably as close to the aneurysmal sac as possible (15,28). There is no
correlation between the size of the aneurysmal sac and paradoxical embolus, although large
sacs are often present in patients with pulmonary hemorrhage (28).
In patients with bilateral PAVM it is our preference to treat one lung at a time, starting with the
most involved lung. Fifteen to 20% of patients develop self-limited pleurisy 3 to 4 days
later, which is attributed to thrombosis of a pleural-based sac and irritation of the visceral
pleura. Occluding PAVM in both lungs at a single session almost guarantees that the patient will
experience pleurisy, which may be bilateral and contributes to their anxiety and fear of
additional procedures. We much prefer to bring the patient back 4 to 6 weeks later to complete
the embolization of the less involved lung and to perform angiography of the first lung
embolized, to assure complete occlusion.
Special considerations include women in the third trimester, when they are particularly prone to
rupture of large PAVMs (29, 30, 31). When a woman entering the third trimester is discovered
to have HHT, urgent screening for PAVM is necessaryand treatment if the PAVMs are large.
Management of children with PAVM is also a special consideration (32). PAVMs frequently
masquerade as asthma or growth failure and large PAVMs may lead to fatal hemoptysis or
hemothorax.
Finally, there is a group of patients with diffuse PAVM, defined originally as all segmental
branches from one lobe or more with small PAVMs arising from all segmental and
subsegmental branches. These patients in general have very small and numerous PAVMs and
are particularly prone to recurrent infection (26). At this writing, we feel that subsegmental
embolization may be indicated in order to raise O2 saturations to a level compatible with
productive life. These patients are best seen at an HHT center with extensive experience with
treating PAVM, since methods for managing diffuse PAVM are undergoing re-evaluation.
PROCEDURAL AND TECHNICAL CONSIDERATIONS

Access, Hemodynamics, and Diagnostic Angiography
An indwelling 7-Fr sheath is placed in the right or left femoral vein and connected to a
heparinized flush solution, being careful to clear the connecting tubing of all air. We access the
pulmonary artery using a 5-Fr pigtail catheter. It is essential that pulmonary artery pressures be
measured in all patients. Most patients with PAVM have low pressures due to their low-
resistance shunts, but in the presence of significant liver malformations, the pulmonary artery
pressures will be raised, with systolic values of 40 to 50 mm Hg. These measurements are an
important clue to the overall state of the patient with HHT and liver involvement (33).
Furthermore in HHT Type 2, there is a subset of patients with primary pulmonary artery
hypertension (34). PAVM, in the setting of pulmonary hypertension with pressures nearing
systemic levels, may be closed, but precautions like 30-min temporary balloon occlusion of a
PAVM in one lung, while measuring pressures in the contralateral pulmonary artery via a
separate catheter introduced from the other femoral vein, seem prudent in such patients.
Patients with polycythemia receive a loading dose of heparin, 100 U/kg, and are kept fully
heparinized during the procedure. Patients with a single PAVM are often done simply with
heparinization of 50 U/kg as a single dose.
Diagnostic angiography in multiple planes is performed in both lungs. The goal is to confirm the
CT findings and, most importantly, to determine the morphology of the artery as it enters the
sac, its length, and its diameter. High-flow arteries <2.5 cm long require special techniques for
closing the PAVM (35).
Following the diagnostic angiogram, the 5-Fr pigtail catheter is exchanged for an 80/100-cm
coaxial guide system with an outer 7-Fr, 80-cm guide catheter and inner 5-Fr, 100-cm
multipurpose end-hole catheter. We prefer to use the 5-Fr catheters to select the feeding artery
with small injections of contrast material and then advance the 7-Fr guide catheter to secure
purchase in the feeding artery.
Since 90% of PAVM are supplied by a single artery, selective fluoroscopic assessments or
hand-injected angiograms in multiple projections are essential before selecting the technique
and placement of fibered coils. The view that profiles the entry of the artery into the aneurysmal
sac, connecting the artery to the vein, is the view of choice for performing the occlusion. This is
an essential step in planning safe deployment of coils and these angiograms are performed
through the 5-Fr end-hole catheter, with the 100-cm, 7-Fr guide catheter securely positioned in
the feeding artery.
Occlusion Techniques and Devices

The vast majority of PAVMs are occluded in our laboratory using the anchor technique with
long, soft, pushable fibered coils (Fig. 33-2). In larger PAVMs with arteries 8 mm in diameter,
the scaffold technique is utilized (Fig. 33-3). The development of these new techniques was
serendipitous and due in part to the manufacturers' discontinuing detachable silicone balloons in
2002.
Since 1978, we had utilized detachable silicone balloons as well as pushable fibered coils and
had found that both worked well (36). The advantage of the detachable silicone balloon was
that it was flow directable. It could be advanced through the guide catheter uninflated, then
partially inflated, and flow directed to the appropriate place in the feeding artery. With both
techniques, we observed with follow-up studies that permanent occlusion was assured if cross-
sectional occlusion of the artery was achieved initially. In other words, permanent cross-
sectional occlusion could be achieved with a single silicone detachable balloon or pushable
fibered coils as long as the coils were packed into a tight coil mass (13,37,38,15).
Nonfibered detachable coils as well as fibered detachable coils are used by some, but we have
found them costly, cumbersome, and time-consuming compared to pushable fibered coils (39,
40, 41). Further occluding the aneurysmal sac of the PAVM removes one of the most important
anatomical signs of successful treatment, i.e., sac involution (see Results and Postprocedural
Management).
Safety during occlusion of PAVM is provided by having a guiding catheter in the feeding artery
and anchoring the first 2 cm of a long and soft fibered coil into a distal side branch, near the
aneurysmal sac, which will be occluded when the artery is completely blocked (Fig. 33-2). This
is the basis of the anchor technique and is used to occlude about 50% of PAVMs in our
laboratory. The first coil placed has a diameter 2 mm larger than that of the feeding, and by
holding the guide catheter in position, the assistant anchors this coil and then retracts the 5-Fr
catheter while deploying the remaining length of the first coil in the artery immediately above or
as close as possible to the aneurysmal sac. In high-flow arteries with diameters 8 mm, we
often anchor the MREYE coil (Cook) first, which has much higher radial force than the platinum
fibered coils. Prior to 2006, when the MREYE coil became available in the United States, we
used conventional stainless-steel coils to form a scaffold or to anchor in large-diameter, high-
flow arteries.
The guiding catheter is a critical part of the formula for obtaining cross-sectional occlusion using
pushable fibered coils since it provides purchase in the artery to be occluded, thus preventing
coil elongation. Coil elongation leads to recanalization (38).
Long-term occlusion of PAVM has been amply documented using pushable fibered coils and
detachable balloons. Use of detachable coils has been published in small numbers, but to
date there appears to be no real advantage to using them for management of PAVM. The
newest device beginning to be used for occluding PAVM is the Amplatzer Plug (42,43). Several
cases using the plug have been reported but there are no long-term studies documenting
permanency of occlusion in PAVM. A theoretical disadvantage of using this device in sensitive
circulations like the lung or carotid is the occlusion time for this device, which averages about
10 min (42,43).
FIGURE 33-2. Anchor technique. This is our technique of choice in 50% to 60% of PAVMs.
A: Standard anatomy of a moderate-sized PAVM with a feeding artery of 4-mm diameter.
The 7-Fr guiding catheter is proximal and the 5-Fr end-hole catheter is used for coil
placement. Many potential anchor arteries are seen just proximal to the aneurysmal sac.
B: Two centimeters of a 6-mm/0.035-in. fibered coil (Cook, Inc., Bloomington, IN) was
placed in the anchor branch and the remaining 12 cm was tightly coiled into a nest in the
proximal feeding artery as close to the aneurysmal sac as possible. This was done by
holding the 7-Fr guide catheter constant and weaving the remaining coil into a tight coil
mass. One additional 4-mm coil was placed and resulted in cross-sectional occlusion of the
artery. C: The postocclusion angiogram demonstrates cross-sectional occlusion of the
artery adjacent to the aneurysmal sac and preservation of normal pulmonary artery
branches.
RESULTS
Satisfactory embolization of small and large PAVMs is readily accomplished in 95% of patients
by experienced teams (15,44, 45, 46, 47, 48, 49). In <5% of patients, the initial diagnostic
study reveals uncertain anatomy, that is, short, high-flow artery, and in these circumstances, a
second diagnostic study may be required and a plan formulated, combining a number of
techniques to effect closure (35). In <1% of patients, use of an occlusion balloon to determine
high-flow anatomy is useful and standard pushable fibered coils (0.038 in) can be advanced
through the second lumen while flow in the large artery is temporarily occluded by the balloon.
Complications most feared are paradoxical embolization of an embolization device, which
occurs in about 1% of patients. Knowledge of vascular snares allows the interventional
radiologist to retrieve these coils (36). In our latest experience we have not experienced a
paradoxical embolization of a device since 1994 in more than 500 consecutive patients (15).
Inadvertent air embolus leading to passage of air through the pulmonary veins and ultimately
into the coronary arteries or cerebral arteries is also preventable but occurred four times during
the course of 200 patient studies recently reported (15). Air accidentally passing into the
coronary arteries produces angina with associated S-T wave changes that lasts ~15 minutes. If
sufficient air enters the cerebral circulation, TIA symptoms including perioral and limb
paresthesias and slight expressive aphasia may be noted but, like angina, clear in <15 minutes.
It is particularly important to clear the catheter of air before introducing guide wires or coils,
and when withdrawing a guide wire, it should be pulled back slowly with the hub of the catheter
under saline in a bowl to avoid the vacuum effect. Filling the catheter with contrast material
between coils allows the interventional radiologist the ability to detect residual air left in the
catheter after withdrawing a guide wire and before pushing the next coil. If air is detected, the
coil is advanced very slowly, thus allowing the slow dissipation and admixture of the air with the
blood.
Following embolotherapy, patients are allowed to get up after 4 hours and they resume normal
activity the next day. In about 15% of patients, a self-limited pleurisy will occur 3 to 4 days after
embolotherapy. It is thought that this is due to irritation of the visceral pleura by thrombosis of
the sac. Now that very distal occlusions are possible by controlled anchoring of the coils in a
small anchor artery adjacent to the sac, it is unlikely that significant pulmonary infarction occurs.
Management of the pleurisy is easily accomplished by administration of ibuprofen for 48 hours,
and hospitalization is rarely required. All patients are instructed about pleurisy when they leave
and
our office is in touch with them frequently during the first week after embolization. Antibiotics
are not prescribed for patients experiencing pleurisy and we are not aware of infection being
associated with the pleuritic episode.
FIGURE 33-3. Scaffold technique. This technique is used for large PAVMs, with arteries
>8 mm in diameter. In this patient, an elderly woman with liver malformations and
moderate pulmonary hypertension, it was thought safer to place the high radial force coils
through an occlusion balloon catheter. A, B: The arterial and venous phases of a selective
pulmonary angiogram in the feeding artery to the malformation. The pulmonary artery
pressures were 50/20, reflecting the underlying high-flow liver malformations. C: The 7/5
Lumax guiding catheter (Cook, Inc., Bloomington, IN) was used to attempt to identify a
suitable anchor vessel near the aneurysmal sac. None was found. D: A 20-mm occlusion
balloon catheter (Boston Scientific, Natick, MA) was placed in the feeding artery and
inflated. The patient was heparinized during the procedure. Oversized stainless-steel coils
15, 12, and 10 mm in diameter were placed in the feeding artery to form an endoskeleton
or scaffold. Once the scaffold is formed, the occlusion balloon catheter is deflated and
the 7/5 Lumax catheter is exchanged for it. Cross-sectional occlusion is obtained by
nesting long platinum fibered coils within the scaffold. E, F: The final occlusion is
demonstrated. G, H: An 8-month follow-up demonstrates no reperfusion. In patients with
pulmonary hypertension, reperfusion is more common and it is our practice to perform a
follow-up pulmonary angiogram at 6 months to 1 year.
A more frightening event is delayed pleurisy, which occurs in <1% of patients at about 3 or 4
months postembolization. It is thought that this is due to delayed thrombosis of the aneurysmal
sac. It may start explosively, with relatively high fever and pleuritic pain. In addition to fluids and
ibuprofen, we have administered a short course of azithromycin (Zithromax) empirically for this
delayed form of pleurisy. In patients with chronic lung disease due to smoking with impaired
pulmonary function, we have also prescribed azithromycin empirically. To date we are not
aware of an infection as a result of embolization for PAVM.
POSTPROCEDURAL MANAGEMENT AND FOLLOW-UP

All patients with treated PAVM should be evaluated by the treatment center at 6 months to 1
year after treatment. Even at experienced centers up to 7% of patients (3% of treated PAVMs)
will have reperfusion of treated malformations and significant enlargement of untreated PAVM
has been
demonstrated in up to 20% of patients (15,46). Our preference is to see the patient at our clinic
and to have a noncontrast CT done immediately prior to our visit, along with supine and
standing pulse oximetry. In our latest prospective study over a period of follow-up that
averaged 6.5 years, we demonstrated that 20% of untreated PAVMs enlarged. Among 155
patients treated, only one of four stroke events during follow-up was due to a PAVM with
paradoxical embolus and this was in a patient with a >3-mm artery that had not been treated
originally. The other three stroke events occurred in older patients commensurate with onset of
atrial fibrillation.
Children reaching adolescence sometimes experience rapid growth of small PAVMs and it is
our feeling that they deserve follow-up every 2 years from age 12 to age 16 (Fig. 33-4
demonstrates extraordinary growth of PAVMs in boys from 12 to 16 years). Women may
experience significant growth of small PAVMs during pregnancy, and as a result we recommend
that they also be seen more frequently postchildbirth (30,31).
FIGURE 33-4. A, B: Computed tomographic images of the lung of a 12-year-old boy with
a large right lower lobe PAVM and 4 years later, at age 16, with marked enlargement of a
left lower lobe PAVM. This patient grew rapidly between age 12 and age 16 and had
marked enlargement of the left lower lobe PAVM. Detachable balloons were used to treat
the right lower lobe PAVM at age 12 and are shown in B.
Finally, since most patients with PAVM have HHT, they may suffer lack of iron replacement for
epistaxis and gastrointestinal bleeding as well as growth and recanalization of PAVMs, and they
deserve to be evaluated by a team that includes the interventional radiologist and other
members of the center for follow-up, minimally, every 5 years (4,15).
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Solid Organ Embolization
Chapter 34
Solid Organ Embolization
Jean-pierre Pelage
Patrick Chevallier
Pascal Lacombe
Embolotherapy is defined as the percutaneous endovascular (arterial or venous) use of a
variety of agents or materials (solid or liquid) to achieve vascular occlusion. Embolotherapy was
first introduced in the late 1970s to control life-threatening hemorrhage in different clinical
settings including upper gastrointestinal bleeding, pelvic trauma, and gynecological malignancy
(1, 2, 3). Its efficacy was also reported earlier in the management of postpartum hemorrhage
and hemoptysis (4,5). In recent years, embolization has become increasingly recognized as an
effective modality for tissue ablation and devascularization of tumors including the liver and the
kidney (6,7). Portal vein embolization (PVE) has been accepted as a valuable tool for organ
flow redistribution to allow increased regeneration of liver parenchyma prior to planned hepatic
resection (8). Ablation of dysfunctioning organs using specific embolization techniques has also
been reported for hypersplenism and immune disorders of the spleen (9). Based on the
experience of arterial embolization in obstetrics, uterine artery embolization has become a
routine technique in the management of uterine fibroids and a valuable alternative to surgery
(10,11). Uterine fibroid embolization has revolutionized the whole area of solid organ
embolization due to a number of significant technical improvements including the development of
calibrated microspheres (12). Chemoembolization of liver tumors has become a key component
of the modern multimodality treatment options of primary and metastatic liver tumors (6,13).
Numerous devices or materials have been used to achieve vascular occlusion. Embolization
materials can be classified into different categories based on their physical and biological
characteristics (Table 34-1). Solid embolization agents include particles and coils. Liquid agents
include acrylic glue, ethanol, and gels. Other devices such as covered stents and thrombin are
usually not used to perform solid organ embolization. The duration of vascular occlusion
depends on the type of vessel (artery or vein), the diameter, and the flow. The type of
embolization material used also influences the durability of vascular occlusion. Gelatin sponge is
considered as a resorbable material associated with temporary occlusion, as opposed to coils
or acrylic glue, which induces a more permanent occlusion. However, apart from the resorption
of the embolization material, recanalization of the occluded vessel may be observed due to
other mechanisms including formation of a new vessel lumen, expulsion of the embolization
material from the vessel lumen or distal migration, and fragmentation of the device (14,15).
Embolization materials can also be classified according to the level of vascular occlusion
obtained from large vessel size to distal arteriolar or capillary levels. Occlusion can be purely
mechanical or may be due to a conjunction of different mechanisms causing vessel wall
destruction by inflammation or sclerosis. Proximal mechanical occlusion is expected with the
use of coils or gelatin sponge pledgets (Table 34-1). Mechanical embolization is also achieved
with the use of nonspherical polyvinyl alcohol (PVA) particles or calibrated microspheres (Table
34-1) (14,16). The level of arterial occlusion may vary (proximal or distal) with nonspherical
PVA particles, whereas a more targeted occlusion can be achieved with calibrated
microspheres (14, 15, 16). For instance, with small calibrated microspheres a reliable occlusion
of small vessels can be achieved, and this is important for targeted tumoral devascularization
(17). Absolute ethanol is a liquid sclerosing agent used to perform preoperative renal artery
embolization and PVE (18,19).
Embolotherapy is a delicate balance between safety and efficacy. The decision to perform
embolization is usually taken by a multidisciplinary team of diagnostic and interventional
radiologists and clinicians (oncologists, gynecologists, surgeons). The key to successful solid
organ embolization depends on a very meticulous process combining different clinical,
radiological, and technical steps: clinical appropriateness of embolization (based on symptoms
and clinical evaluation), proper preprocedural imaging evaluation using recent technologies such
as multidetector-row computed tomography (MDCT), and magnetic resonance imaging (MRI)
with relevant vascular reconstructions, accurate determination of the target (tumor, vessel
diameter) during pre-embolization angiography, careful selection and use of the embolization
material, and availability of a trained interventional radiologist, who should also be involved in
the follow-up of treated patients (clinical involvement and imaging studies).
The most common side effect of embolotherapy is postembolization syndrome, reported mainly
after embolization of solid organs (20). Postembolization syndrome consists of low-grade fever,
pain, nausea or vomiting, general malaise, and leukocytosis. These symptoms start shortly
after embolization and may last several days, usually 1 week (20). Symptoms associated with
postembolization syndrome are often self-limiting and require only supportive therapy. However,
the differential diagnosis includes extensive tissue infarction or infection, particularly after
arterial chemoembolization of the liver or splenic artery embolization (20, 21, 22). Radiologists
should be able to distinguish postembolization syndrome and a complication in case of unusual
manifestations such as vaginal discharge of pus after uterine fibroid embolization (UFE) or high-
grade fever after arterial chemoembolization of the liver (21,23).
In this section, we discuss the different characteristics and indications of embolization agents
used to perform solid organ embolization. Four different common indications of embolotherapy
will then be detailed including renal, splenic, and uterine artery embolization, as well as liver
embolization on both the arterial and the portal venous sides. Trauma-related hemorrhage
involving solid organs and requiring the use of embolization is treated in another chapter.
TABLE 34-1 EMBOLIC MATERIALS USED FOR SOLID ORGAN

EMBOLIZATION
Device Company(ies)
Embolization particles
Caps recherche, Ethicon, Rusch

Gelatin sponge
Pilling
Regular PVA particles Boston Scientific, Cook
Embosphere, Tris-acryl microspheres Biosphere Medical
Bead Block, PVA microspheres Terumo
Contour SE, PVA microspheres Boston Scientific
Chargeable or loaded microspheres
Hepasphere Biosphere Medical
DC Beads Biocompatibles
Radioactive microspheres
90Y glass microspheres, Theraspheres Nordion
90Y resin-based microspheres, SIR-

Sirtex
spheres
Liquid embolization agents
Ethanol American Regent
Acrylic glue (Histoacryl, Trufill) B-Braun, Cordis
Coils
0.035/0.038 coils and microcoils Boston Scientific, Cook

EMBOLIZATION AGENTS FOR SOLID ORGAN EMBOLIZATION
Gelatin Sponge
Gelatin sponge has been extensively used for 30 years to perform embolization, particularly in
the management of obstetrical hemorrhage (4,15,24). Gelatin sponge is a foamlike material
initially used to obtain hemostasis during surgery. It is a biodegradable material considered as a
resorbable agent. Three forms are available from different companies: a powder containing
small fragments, a sheet from which sections of different sizes can be cut, and thicker blocks
allowing one to obtain large pledgets (Fig. 34-1 and Table 34-1). The gelatin sponge powder is
associated with a high risk of ischemia and is currently not recommended (24). Pledgets
measuring 1 2 to 3 3 mm, manually cut into strips with scissors or scalpel and then rolled,
are particularly suitable for hemostatic embolization in general and for pelvic or splenic
embolization (15). The pledgets are usually placed into 1- or 2-mL syringes with saline and
contrast material. Gelatin sponge slurry obtained by mixing small pledgets with contrast is
commonly used during chemoembolization of the liver. A proximal mechanical arterial occlusion
is obtained, followed by thrombosis and acute necroziting arteritis (15,25). Arterial
recanalization is usually observed within hours to weeks after embolization and has been
reported even after long-term occlusions (Fig. 34-2) (15,25).
Nonspherical Polyvinyl Alcohol Particles

Nonspherical (also called regular) PVA particles have been used as an embolization agent in
various vascular distributions for more than 20 years (Table 34-1) (26,27). The irregular shape
of the material is associated with a larger granulometric distribution of the particles than
advertised (Fig. 34-3) (28). In addition, there is a risk of injection of particles smaller than the
theoretical size in conjunction with aggregates (28,29). This adverse effect of regular PVA,
potentially leading to extensive necrosis, has been reported several times (30). In clinical
practice, clumping of regular PVA particles can lead to obstruction of the catheter or
microcatheter and, potentially, to uncontrolled levels of arterial occlusion (15,28,30). With
nonspherical particles, clumping of the embolization material may result in a false angiographic
end point at the conclusion of the embolization. The mechanism of arterial occlusion induced by
regular PVA particles is well understood: The initial incomplete lumen occlusion by the particles
is associated with thrombus formation within the interstices (Fig. 34-4) (26). Recanalization of
the embolized artery is usually observed after several months or years. Several mechanisms
such as distal migration, fragmentation or extravascular migration of PVA particles, and
resorption of thrombus may account for arterial recanalization (31). Nonspherical PVA particles
have been extensively used to perform renal, splenic, liver embolization, and UFE
(6,11,15,23,31, 32, 33).
FIGURE 34-1. Gelatin sponge cubes are particularly suitable for hemostatic embolization.
Tris-Acryl Gelatin Microspheres

Tris-acryl gelatin microspheres have been developed in France to address some of the
disadvantages associated with nonspherical PVA particles and have been used in Europe since
1994 in various territories (Table 34-1) (16,34,35). Microspheres are spherical, precisely
calibrated, microporous, cross-linked acrylic beads embedded with gelatin (Fig. 34-5) (16,35).
The spheres are compressible, which allows easy passage through a microcatheter with a
luminal diameter smaller than that of the microspheres (35). A better distribution of Tris-acryl
microspheres than nonspherical particles has been observed after injection into the rete
mirabile of pigs and into the uterine arteries of sheep (35,36). It has been demonstrated that
the degree of penetration of the particles into the vascular system was different for
nonspherical PVA and Tris-acryl microspheres (36). A significant correlation between the level
of arterial occlusion and the diameter of the particles used was observed for all sizes of Tris-
acryl microspheres (Fig. 34-6) (36). Thus, a reproducible deeper penetration of embolic
particles results in a more effective tumoral devascularization of many hypervascularized lesions
including uterine fibroids, meningiomas, and hepatocellular carcinomas (17,36). In a renal artery
embolization animal model, the blood flow was more quickly and reliably reduced using Tris-
acryl microspheres than with nonspherical PVA (37). Since the mechanism of occlusion is
different from that of nonspherical PVA, with a small number of microspheres occluding a
vessel of the corresponding size, a more segmental arterial occlusion is obtained (17,36). In the
long-term, there is no chronic inflammatory reaction and no degradation of the polymer (16).
The experience with arterial embolization using Tris-acryl microspheres is growing rapidly for
uterine artery and hepatic artery embolization (12,38). The initial experience with PVE is also
very promising (39).
FIGURE 34-2. Life-threatening postpartum hemorrhage after vaginal delivery in a 35-year-

old woman. A: Nonselective embolization of both internal iliac arteries (arrows) was
achieved using large pledgets of gelatin sponge. B: Control angiography obtained 4 hours
later because of recurrence of bleeding shows recanalization of the embolized left internal
iliac artery.
FIGURE 34-3. Regular polyvinyl alcohol particles have an irregular shape and calibration.
These properties do not guarantee targeted vascular occlusion.
FIGURE 34-4. Photomicrograph of a high-power section through the periphery of an
intramural fibroid removed immediately after embolization. Premyomectomy uterine artery
embolization was performed using 355- to 500-m nonspherical PVA particles. The
embolized artery shown contains aggregates of polyvinyl alcohol particles (black).
Thrombus is also seen within the interstices. (Hematoxylin safran and eosin; original
magnification, 400.)
FIGURE 34-5. Embosphere Tris-acryl microspheres (Biosphere Medical, Louvres, France)
are precisely calibrated, spherical hydrophilic microporous particles.
FIGURE 34-6. A 33-year-old woman with uterine fibroids treated with premyomectomy
embolization of the uterine arteries. Photomicrograph of a high-power section through the
periphery of an intramural fibroid resected immediately after embolization using 500- to
700-m Tris-acryl microspheres. The artery shown is occluded by Tris-acryl microspheres.
Cross-sectional arterial occlusion is obtained by one microsphere. (Hematoxylin safran and
eosin staining; magnification, 200.)
FIGURE 34-7. Prepacked syringe of Bead Block polyvinyl alcohol hydrogel microspheres
(Biocompatibles, Farnham, UK).
Spherical Polyvinyl Alcohol Particles

Because of the unpredictable behavior of nonspherical PVA particles, and in light of the
theoretical and published advantages of Tris-acryl microspheres for neurologic and gynecologic
interventions, PVA microspheres from two different companies have received CE and FDA
approval (Figs. 34-7 and 34-8, Table 34-1) (40,41). The decision to use PVA as the core
constituent was based on the long track record of safety and efficacy of this material in
embolization procedures. Large PVA microspheres are easy to inject through microcatheters.
Initial animal studies demonstrated that PVA microspheres are effective embolization particles
associated with a similar degree of targeted renal parenchymal infarction as Tris-acryl
microspheres (40,41). PVA microspheres were associated with a milder inflammatory reaction
compared to regular PVA particles (40). Initial experimental studies suggested that PVA
microspheres tended to travel more distally than the irregular PVA particles (41). In addition, it
has been demonstrated that the degree of penetration of the particles into the vascular system
is different for PVA spheres and Tris-acryl spheres (41). PVA spheres always occluded at a
more distal level than Tris-acryl spheres, probably because of different compressibility
properties (Fig. 34-9) (41). Even if the clinical experience with the use of PVA spheres is limited
to date, the interventional radiologist should consider upsizing particles when PVA microspheres
are used instead of Tris-acryl microspheres.
Drug-Eluting Microspheres
Another potential application of embolotherapy is to use the microspheres as a platform to
deliver medications (Table 34-1)
(42). Technology developed for other applications (e.g., stents) is being applied to drug-eluting
embolic devices. The first products already available in the field of interventional radiology have
been developed to treat liver disease (42). Two types of microspheres are available: those that
behave like sponges able to absorb large amounts of drugs in solution (Hepasphere, Biosphere
Medical) and those produced from specific polymers able to adsorb a given drug that reaches
a high concentration inside the biomaterial (DC Beads; Biocompatibles) (Figs. 34-10 and 34-11)
(42,43). In the first case the release system can be considered as a ready-to-load platform for
water-soluble drugs,
but a release can occur in the medium before and during injection. In the second one, the
product is more likely to have a longer sustained release. The first clinical trials are ongoing and
preliminary results may be published soon.
FIGURE 34-8. Vial of Contour SE polyvinyl alcohol microspheres (Boston Scientific, Natick,
MA, USA).
FIGURE 34-9. In vitro compressibility of three types of calibrated microspheres available
on the market. Contour SE (Boston Scientific, Natick, MA, USA) and Bead Block
(Biocompatibles, Farnham, UK) polyvinyl alcohol microspheres are more compressible than
Embosphere Tris-acryl microspheres (Biosphere Medical, Louvres, France).
FIGURE 34-10. Hepasphere superasborbent polymer microspheres (Biosphere Medical,
Louvres, France). Placed in saline, one of these microspheres has a diameter ~3.5 times
larger than its original size in the dry state. This capacity can be used to absorb
chemotherapeutic agents.
FIGURE 34-11. Vial of doxorubicin-eluting beads in saline (Biocompatibles, Farnham, UK).
The next generations of microspheres may be charged with vasoactive or anti-angiogenic drugs
to enhance the local action or prolong the duration of arterial occlusion. Similarly, drug-loaded
microspheres for UFE can be loaded with hormones or growth factor inhibitors. Finally,
analgesics or anti-inflammatory drugs may be loaded in order to reduce postprocedure pain,
particularly after hepatic artery or uterine artery embolization. The theoretical advantages of
drug-loaded embolization particles include higher local concentrations and lower total doses of
drug compared to a systemic administration.
Detectability of embolization particles has long been a matter of debate among interventional
radiologists. Because of their high water content, current particles are not detectable by
fluoroscopy, MDCT, or MRI, and operators cannot localize them during and after embolization.
Radiopaque particles may be used to perform embolization without adding iodinated contrast
material. Localizing the distribution of microspheres after arterial embolization of the liver may
help detection of nontarget embolization, control of the homogeneity of distribution of the
particles, evaluation of the intra- or extratumoral location of microspheres, and follow-up of the
migration of microspheres during time. Microspheres that are detectable with MRI have been
developed recently (Fig. 34-12). Postembolization MRI may be used to detect these
microspheres, as is done with noncontrast MDCT after chemoembolization of the liver to
evaluate lipiodol aggregation. Other clinical applications may include embolization of uterine
fibroids and brain tumors.
Radioactive Microspheres
As in the case for transarterial chemoembolization, radioembolization takes advantage of the
preferential hepatic arterial supply of hepatocellular carcinoma (HCC) or vascular metastases
to deliver targeted therapy to the tumor, relatively sparing the liver parenchyma, which is mostly
supplied by the portal venous system. Radioembolization is affected via intra-arterial delivery of
carrier spheres onto which radioactive particles are attached. There are two types of
radioactive microspheres that can be used in the treatment of primary and metastatic liver
disease (Table 34-1) (44, 45, 46). They both contain yttrium-90 (90Y) as the active element but
differ in the type of carrier particle. The first is 90Y glass microspheres (Theraspheres; MDS
Nordion, Ottawa, ON, Canada, which are glass spheres with a diameter of 25 10 m
impregnated with 90Y, which is a radioactive element (44,45). Following intra-arterial infusion,
most Theraspheres embolize at the arteriole level because of their diameter. After lodging in
the distal arteriolar circulation, the microsphere radiation has a maximum effective tissue
penetration of 10 mm, thereby sparing the normal liver parenchyma beyond this limit. Radiation
essentially ceases ~10 days after radioembolization. The second type of 90Y carrier is a resin-
based microsphere with a diameter of 29 to 35 m, also infused via the appropriate hepatic
artery branch to provide selective internal radiation. These SIR microspheres (Sirtex Medical
Ltd., Lake Forest, IL, USA) have an average activity of 40 Bq per sphere and can be
suspended in sterile water and contrast medium to the desired total activity (44,46). Since the
radioactive element is the same as that on glass microspheres, the tissue penetration and
decay properties are identical, as are patient selection, preparation, and technique.
FIGURE 34-12. In vivo detectability of 700- to 900-m MR marked microspheres after
renal artery embolization in a sheep. MRI study of the explanted kidneys was performed
24 hours after embolization (T1 SE, TR 450, TE 10, FA 90 degrees; 192 256; slice
thickness, 1.5 mm). MR marked microspheres (stars) are easily detected in the different
branches of the renal arteries.
The use of radioembolization microspheres has been limited because of very restrictive
conditions of use and strict patient selection. The total dose to be delivered depends on the
tumor burden and the liver volume based on imaging evaluation (CT or MRI). A total dose of
120 to 150 Gy is considered to be optimal. Then the degree of shunting between the hepatic
artery and the hepatic vein needs to be precisely assessed by performing a perfusion study of
the liver with 99Tm macro-aggregated albumin particles (44). The administration of 99Tm macro-
aggregated albumin particles is performed during selective liver arteriography through the
angiography catheter located in the arterial branch that will be used for radioembolization. The
patient is then taken to the nuclear medicine department and planar images of the liver and
lungs are obtained (44). Normal lungs can tolerate a total dose of 30 Gy. If the calculated liver
dose is 120 Gy, the shunt fraction should then be <25%. At the time of radioembolization, a
very specific technique of use with an infusion setup apparatus is used. Intra-arterial
radioembolization has been recently promoted in patients with HCC and colorectal metastases
who do not respond to transcatheter arterial chemoembolization (TACE) or systemic
chemotherapy (45,46).
Coils
Coils are nonrresorbable, nonparticulate, embolic agents (Table 34-1). Initially only stainless-
steel coils were available (18,32). More recently platinum coils, in fibered and nonfibered
variants, have become available (Fig. 34-13). Macrocoils (0.035 and 0.038) and microcoils
(mainly 0.018) are available for injection through regular 4- or 5-Fr catheters or through 2.7- or
3-Fr microcatheters. The choice of a coil of the correct size is critical: a size too small may not
completely occlude the arterial lumen. Too large, the coil may cause occlusion of proximal
arterial branches or may elongate, leading to recanalization. After placement of the first coil,
additional coils must be positioned until arterial blood flow has ceased (18,32). If the number of
coils is not sufficient, recanalization may also occur because of insufficient thrombosis formation
(18,32). Coils are the first-line embolization agent to perform
partial splenic embolization (47). Coils can also be injected as a secondary embolic agent in
conjunction with particles for arterial or PVE procedures (18,32,39). However, the use of coils
increases the cost of the procedure and may prevent reembolization if necessary (48).
FIGURE 34-13. Different types of fibered coils or microcoils. Coils allow a durable arterial
occlusion of embolized vessels.
Acrylic Glue
N-Butyl-cyanoacrylate, also called acrylic glue, is a fastpolymerization tissue adhesive of low
viscosity that appears to be one of the best agents for complete occlusion of large to medium-
sized arteries (Table 34-1) (18,49). Acrylic glue polymerizes on contact with ionic solutions,
such as normal saline, contrast material, and blood, and with the intima of the vessels.
Therefore the delivery system must be flushed with 5% glucose to delay polymerization and
avoid gluing of the vessel wall. The polymerization time can be delayed by adding lipiodol in the
mixture (Fig. 34-14). The ratio of cyanoacrylate to lipiodol depends on the level of arterial
occlusion required. The more lipiodol in the mixture, the longer the polymerization time of the
glue and the more distal occlusion is achieved. For instance, a ratio of between 1:2 and 1:3 is
recommended to perform PVE. The presence of lipiodol makes the mixture radiopaque, which
increases the level of safety at the time of embolization. Some authors may even consider
adding some tantalum powder to increase the radiopacity (Fig. 34-14). A mechanical occlusion
of the target artery is obtained, followed by a intense inflammatory reaction (18,49).
Cyanoacrylate is considered as a definitive embolic agent even if recanalization may occur in
the long term. Special training with the use of acrylic glue is required and has limited the
acceptance of this embolic agent (18,49). Acrylic glue has been widely used to perform PVE
and, occasionally, for arterial liver chemoembolization (50,51).
Other Embolization Devices

Ethanol administered as an intra-arterial agent induces endovascular endothelial damage and
tissue protein denaturation, resulting in permanent vascular occlusion and tumor infarction
(Table 34-1). Its efficacy as an embolic agent has been demonstrated in experimental studies
of and clinical experience with renal or PVE (52,53). The use of balloon-assisted occlusion
technique is widely accepted to reduce the risk of retrograde reflux of the agent, especially
during renal procedures. For complete renal embolization, 0.2 mL/kg body weight of absolute
ethanol (99% ethyl alcohol) is typically perfused in a mixture with nonionic contrast material for
appropriate control under fluoroscopy (54). Vascular occlusion induced by ethanol is more
peripheral than that induced by most other agents (55). The main advantages of an ethanol
agent for embolization purposes are its minimal cost, universal availability, high efficacy for
tumor and renal infarction, and low complication rate when used with a balloon-assisted
occlusion technique. No postembolization recanalization of vessels embolized with ethanol has
been reported in animal studies (55).
FIGURE 34-14. Acrylic glue (small vial) is mixed with lipiodol. Tantalum powder (black
sheet) can be added to increase radiopacity.
RENAL ARTERY EMBOLIZATION

Introduction
Malignant tumors of the kidney account for ~5% of all adult malignancies. Renal cell carcinoma
is the most common primary malignant tumor of the kidney and occurs in both sporadic and
hereditary form (56). Renal cell carcinoma may remain clinically occult for most of its course.
The basis of treatment of localized renal cell carcinoma is surgical resection, as the disease is
relatively resistant to both radiotherapy and chemotherapy (47). Historically, radical
nephrectomy was considered the only effective treatment for patients with renal cell carcinoma.
More recently, nephron-sparing surgery has been developed as an alternative for small tumors
(<3 to 4 cm) localized to the kidney (58). Minimally invasive therapies including transarterial
embolization, cryotherapy, and radiofrequency ablation have been recognized as new
approaches to treat renal cell carcinoma, mainly in patients who are not good surgical
candidates. For large tumors, renal artery embolization was popularized as an adjunct to
surgery to reduce preoperative bleeding. Since that time, embolization has been used before
resection of larger tumors and tumors invading the renal vein or inferior vena cava (59).
Angiomyolipoma is generally a benign tumor of the kidney, although a more aggressive subtype
has also been described (60). Angiomyolipoma may be associated with tuberous sclerosis
disease or is encountered sporadically. Clinically, patients may present with flank pain, a
palpable mass, or macroscopic
hematuria (60). The most dramatic and life-threatening presentation of angiomyolipoma is
spontaneous retroperitoneal hemorrhage, encountered mainly in case of large masses. Most
angiomyolipomas are now treated conservatively with selective surgical resection to control
symptoms, to prevent complications, and to preserve renal function. Recently, selective arterial
embolization has been reported to treat angiomyolipomas (61).
Malignant Renal Tumors

Technical Considerations
A flush abdominal aortogram is usually performed to determine the number and location of
arteries supplying the kidney and the tumor except if vascular reconstructions have been
obtained with MDCT (Table 34-2). Selective catheterization and evaluation of each feeding
artery are then performed to assess the extent of neovascularity and the degree of
arteriovenous shunting. Most renal cell carcinomas appear hypervascular on angiography and
demonstrate tumor vessels that are irregular and tortuous (Fig. 34-15) (62). Other findings may
include arteriovenous shunting, staining of the tumor during the capillary phase, and renal vein
invasion. The size and extent of the tumor, the need to preserve parts of the surrounding renal
parenchyma, and the overall goal of embolization (preoperative vs. definitive embolization)
should be considered in planning embolotherapy of renal tumors. In most published studies,
liquid agents (mainly absolute ethanol), particulate materials (the prototypes of which are
nonspherical polyvinyl alcohol particles and calibrated microspheres), and metallic coils have
been used (Table 34-2) (62). Ethanol is injected into the main renal artery and diffuses into the
distal vascular bed of the tumor, causing tumor necrosis (52). Transcatheter administration of
ethanol is technically easy, but reflux of ethanol should be prevented by using an occlusion
balloon catheter (52). The desired angiographic end point is described as occlusion of all
arteries smaller than major segmental branches, with stagnation of flow in patent larger
arteries.
FIGURE 34-15. Large right renal cell carcinoma in a 66-year-old man. A: Preoperative
digital subtraction angiography after selective injection into the right renal artery shows
diffuse renal hypervascularization (stars). B: After embolization using pledgets of gelatin
sponge and coils (arrows), satisfactory arterial occlusion is achieved.
TABLE 34-2 EMBOLIC MATERIALS AND CATHETERS USED FOR RENAL

ARTERY EMBOLIZATION
Recommended device Company(ies)
Abdominal aortography
Angiodynamics, Cook, Merit Medical,

Pigtail catheter, 5-F
Terumo
Selective renal arteriography
C2 Cobra, 5 Fr Cook, Terumo
Sos Omni selective, 5 Fr Angiodynamics
Occlusion balloon catheter, 5 Fr Boston Scientific
Superselective catheterization
Renegade Hi-Flo, 3 Fr Boston Scientific
Progreat 2.7 or 2.8 Fr Terumo
Embolization materials
Ethanol American Regent
Embosphere, Tris-acryl
Biosphere Medical
microspheres
Gelatin sponge Caps Recherche, Ethicon, Rusch Pilling
Coils Boston Scientific, Cook
Particulate materials, such as absorbable gelatin sponge and nonspherical PVA particles, have
been used alone and with metallic coils (Fig. 34-15, Table 34-2) (62). Later generations of
embolic agents such as calibrated Tris-acryl microspheres and PVA microspheres are also
used for embolization of renal masses, but only preliminary reports of their effectiveness are
available in the literature (Table 34-2). In general, distal embolization of the tumor bed, rather
than proximal occlusion, is desirable. Therefore, embolization should start with particles small
enough to avoid proximal occlusion. In tumors with rapid arteriovenous shunting, the use of
larger particles may be prudent to avoid non-target lung embolism. The use of coils for
palliation of tumors is discouraged because renal tumors in advanced stages often have an
extensive collateral blood supply, rendering proximal occlusion of the feeding arteries
ineffective.
For preoperative embolization, the use of regular PVA particles, calibrated microspheres, and
gelatin sponge pledgets is usually favored (Fig. 34-16).
Results
Almgard popularized renal artery embolization in the early 1970s (63). Over the next two
decades, investigators debated the usefulness of arterial embolization to treat renal cell
carcinoma. In 1999, Kalman and Varenhorst published a survey of the literature on renal artery
embolization for management of renal cell carcinoma (62). Recruitment of patients in the
studies on preoperative embolization varied widely. Some investigators included patients with
large tumors only (64). The time between embolization and nephrectomy varied between a few
hours and up to 6 months. The optimal delay between embolization and operation is supposed
to be 48 hours. Clinical indication for palliative embolization included abdominal or flank pain,
hematuria, and severe endocrine tumor activity (65, 66, 67).
FIGURE 34-16. Left renal cell carcinoma of the kidney in a 30-year-old man with
intractable hematuria. A, B: Pre-embolization digital subtraction angiography after selective
injection into the left renal artery shows diffuse tumoral hypervascularization (stars)
consistent with carcinoma. C: Distal tumoral devascularization is achieved (arrows) after
targeted embolization using 300- to 500-m Tris-acryl microspheres (Embospheres) and
gelatin sponge pledgets.
Several variables have been considered in measurement of the intended outcome, including
intraoperative blood loss. In three studies, the difference in the amount of blood loss in
embolized versus nonembolized patients was not statistically significant (42,43,51). Bakal et al.
demonstrated that estimated blood loss is an unreliable measurement and instead used the
transfused volume as a measure of successful preoperative embolization (59). They
demonstrated that the transfusion volume was statistically significantly lower after embolization
for patients with large hypervascular renal cell carcinoma than for smaller or hypovascular
tumors. In a recent study, preoperative
embolization resulted in improved survival after nephrectomy: the overall 5- and 10-year survival
rates were 62% and 47%, respectively, for 118 patients embolized before nephrectomy and
35% and 23%, respectively, for a matched group of 116 patients treated with surgery alone
(68). Palliation of symptoms in nonsurgical candidates was also used as an evaluation criterion.
In one study, severe hematuria resolved in 11 of 14 patients, and incomplete embolization of the
tumor resulted in persistent hematuria in 3 of 14 patients (65).
Major complications have occasionally been reported as a result of nontarget embolization of
the large bowel, spinal cord, contralateral kidney, or gonadal artery (64,69). Lammer et al.
reported a 10% overall complication rate in 121 renal tumor embolizations and a mortality rate
of 3% (64). The most common complications in this series were renal failure and nontarget
embolization (64).
Other Indications
The angiographic appearance of angiomyolipoma is that of a hypervascular mass with a large
feeding artery. The vascular components of the tumor are thick-walled arteries characterized by
the absence of the internal elastic membrane and a disordered adventitial cuff of smooth
muscle, which results in the numerous saccular aneurysms frequently seen on arteriograms.
Tortuous vessels may be circumferentially arranged in the arterial phase. Overall, a sunburst or
whorled appearance in the nephrographic and venous phases is suggestive of these tumors.
Arteriovenous shunting is not a prominent feature of angiomyolipomas. Different technical
approaches have been promoted to embolize angiolipomas (61,70,71). Different types of
embolization agents including ethanol, coils, and regular PVA particles have been successfully
used alone or in combination (PVA particles and coils) (Table 34-2) (61). A combination of a 1:3
mixture of iodnized oil and alcohol has also been proposed. In all cases, the desired
angiographic end point is complete devascularization of the tumor on control angiogram (71).
Results
Nelson and Sanda summarized recent studies relevant to the clinical management of renal
angiomyolipoma (72). Among other factors, the authors cited refinement of the technique of
embolization as a major development in the management of these benign tumors. The most
common indication for embolization was acute hemorrhage (retroperitoneal bleeding or
hematuria). Other indications were symptomatic tumors in patients who were poor surgical
candidates or had limited renal reserve and asymptomatic tumors for which prophylactic
treatment was chosen. From a clinical point of view, embolization is effective in 40% to 80% of
symptomatic patients. Over a median follow-up of 24 months, 17% of patients had recurrent
symptoms or hemorrhage that required repeat embolization or surgery (73). The effectiveness
of selective arterial embolization can also be evaluated on the basis of the area of the
angiomyogenic components on follow-up CT images. In one study with long-term CT follow-up,
nearly all angiomyogenic components disappeared, but fatty components partially shrank with
liquefactive necrosis in tumors (71). Postembolization syndrome was recorded for 85% of
patients. Other complications were reported in about 10% of cases including sterile
liquefaction, renal abscess requiring drainage (5%), and pleural effusion (3%).
SPLENIC ARTERY EMBOLIZATION

Introduction
Splenectomy is often performed for the management of hypersplenism, which is associated
with increased destruction of the corpuscular elements of the blood by the spleen, resulting in
reticuloendothelial hyperplasia (74). Hypersplenism may be seen in various disorders, including
splenic infiltration from primary malignancies such as leukemia and lymphoma, cirrhosis with
portal hypertension, and hematological diseases including idiopathic thrombocytopenic purpura
and thalassemia major (9,75, 76, 77). Patients with hypersplenism may present with various
symptoms including abdominal discomfort, pain, splenomegaly, and biological abnormalities
such as thrombocytopenia, leukopenia, and anemia (78). Total splenectomy may be an
effective treatment for hypersplenism but predisposes treated patients to sepsis because of
impairment of the ability to produce antibodies against encapsulated micro-organisms. During
the past three decades, splenic arterial embolization has been advocated in the nonoperative
treatment of patients.
After numerous reports of severe complications resulting from complete splenic infarction, many
authors have advocated incomplete or partial splenic embolization, a method by which a portion
of the splenic parenchyma is left viable, thus preserving the immunologic function of the spleen
and limiting the risks of complications (77,78). Splenic embolization has also been advocated as
a preoperative tool to improve the safety of, and reduce intraoperative blood loss during, open
or laparoscopic splenectomy (79).
The splenic artery supplies the spleen as well as portions of the stomach and pancreas. Near
the splenic hilum, the artery usually divides into superior and inferior terminal branches, and
each branch further divides into segmental intrasplenic branches. The superior terminal
branches usually provide the dominant splenic arterial supply. The inferior polar artery usually
provides the left gastroepiploic artery, but it may also arise from the distal splenic artery. The
left gastroepiploic artery then runs along the greater curvature of the stomach. Numerous short
gastric branches arise from the terminal splenic or left gastroepiploic artery to supply the
gastric cardia and fundus. The splenic artery also has many branches such as the pancreatica
magna and dorsal pancreatic artery to the body and tail of the pancreas. When arterial
embolization is performed, identification of these arteries is mandatory to reduce the risk for
nontarget embolization. Proximal splenic arterial embolization is usually not effective because of
the numerous collateral branches from the short gastric and gastroepiploic arteries that re-
establish the blood supply to the spleen around the occluded segment of the splenic artery
(80). Conversely, the aggressive arterial embolization technique (embolization to stasis) using
autologous clots or small particles has been abandoned because of the high incidence of
complications such as splenic abscess, splenic rupture, and septicemia (81).
Recently, different strategies have been discussed to find the optimal approach in terms of
safety (incidence of complications) and efficacy (hemodynamic and hematological response).
Embolization of 60% to 70% of the splenic parenchyma seems to be the best ratio (9,77,78).
Preprocedural protocol should also include broad-spectrum antibiotics started before
embolization and continued for up to 14 days, administration of a pneumovax vaccine
(commonly offered before splenectomy) to prevent pneumococcal infection, and
strict attention to sterility at the time of embolization. The use of local antibiotics suspended in
the solution used to deliver the embolization particles has also been proposed (78).
TABLE 34-3 EMBOLIC MATERIALS AND CATHETERS USED FOR

SPLENIC ARTERY EMBOLIZATION

Pigtail catheter, 5 Fr
Terumo
Selective splenic arteriography
C2 Cobra visceral, 5 Fr Cook, Merit Medical, Terumo
Sos Omni Selective, 5 Fr Angiodynamics
Progreat, 2.7 or 2.8 Fr Terumo
Embolization agents
Biosphere Medical
microspheres

Gelatin sponge Caps recherche, Ethicon, Rusch Pilling
Coils Boston Scientific, Cook
The catheter tip should be placed proximally in the main splenic artery distal to the origin of
major pancreatic branches (Table 34-3). Embolization particles should be injected slowly until
the parenchymal blush is reduced angiographically (Table 34-3). Other groups favor a more
targeted distal devascularization where distal branches of the splenic artery are selectively
catheterized and embolized to complete stasis and several other branches are left patent. The
embolic agents most commonly used for splenic artery embolization are gelatin sponge
pledgets, large regular PVA particles or microspheres, and coils (Fig. 34-17, Table 34-3)
(80,82).
Results
The effect of the limited embolization technique, where only 30% of the splenic mass was
ablated, was evaluated and it was concluded that the reduced infarction volume still led to
increased platelet counts (83). Therefore, a more conservative embolization procedure with
lower complication rates may be prudent, and a second embolization can be performed if
necessary. Reported complications include pancreatitis (likely a result of nontarget embolization
of dorsal pancreatic and pancreatica magna arteries), pleural effusion requiring drainage,
paralytic ileus, and postembolization syndrome.
Numerous other studies have demonstrated that splenic embolization is an effective therapeutic
alternative to splenectomy in patients with hypersplenism (78,80,82). Kimura et al. reported the
results of initial and repeated sessions of embolization in patients with idiopathic
thrombocytopenic purpura. Twenty patients (50%) responded to the initial embolization (11
complete response, 9 partial response). Of the 11 patients with complete response at a median
follow-up of 58 months, only 1 patient had a recurrence and underwent repeat embolization. Of
the nine patients with a partial response, four maintained a platelet count of >50,000/mm3
without recurrence during a median follow-up period of 5 years.
LIVER EMBOLIZATION
Introduction
HCC continues to be one of the most common lethal malignancies in the world, and the
prognosis for patients with HCC is poor. Although surgical resection remains the only hope for
cure, very few patients (10%) are candidates (84). TACE is, by far, the most common
technique used to treat unresectable HCC (6). Chemoembolization is based on the fact that
primary hepatic tumors (HCCs) are nearly exclusively supplied by branches of the hepatic
artery whereas normal liver parenchyma derives most of its blood supply (75%) from the portal
venous system (85). Transcatheter arterial chemoembolization selectively targets the tumor,
while liver parenchyma is mostly spared. The true mechanism by which TACE induces tumor
necrosis remains unknown, and therefore, there is no consensus opinion on the most effective
technique. Some metastatic liver nodules, mainly from neuroendocrine tumors, may also derive
their blood supply from the hepatic artery (38). Theoretically, then, chemoembolization can be
used to treat any solid malignant hepatic neoplasm, whether primary or metastatic, solitary or
multifocal, and irrespective of size (6,38,86,87). Despite the numerous techniques used during
the years, the term chemoembolization implies localized intraarterial delivery of some sort of
chemotherapeutic agents, emulsified in an oily medium, combined with embolic material. The
combination of highly concentrated chemotherapy and some degree of ischemia within the
tumor is likely to be synergistic in achieving tumor necrosis (86). Embolization allows higher
concentrations of chemotherapeutic agents within the tumor than after systemic chemotherapy.
Because embolization reduces inflow to tumors, the chemotherapeutic agent will remain in
contact with the tumor cells for a prolonged time. A number of chemotherapeutic agents have
been used to perform TACE, and controversy persists regarding the selection of the drug
(6,87). The most common chemotherapeutic drug used as a sole agent or in combination with
cisplatin and mitomycin C is doxorubicin (87). The rationale for using an oily medium during
TACE is based on observations that poppy seed oil accumulates preferentially in HCC (87). In
addition to being a tumor-seeking agent, the oily medium is also a drug-carrying (if proper
emulsion is obtained) and embolization material. After injection of the mixture (chemotherapy
and lipiodol) additional embolization includes delivery of gelatin sponge pledgets or regular PVA
particles to reduce the arterial inflow to the tumor. The issue of selective catheter placement
(lobar versus segmental) during TACE remains controversial. It is generally recommended to
use a superselective or selective positioning of the catheter when a single or a small number of
lesions is present, whereas a less selective approach should be applied in the case of multiple
tumors in one lobe (Figs. 34-18 and 34-19). Child A and B patients are particularly suitable for
TACE, whereas the risks of complications are higher in Child C patients (87).
Considering the advantage of more peripheral embolization with the use of a permanent
embolization agent alone to increase tumor ischemia and spare chemotherapeutic agents,
superselective transarterial embolization has recently been proposed to treat HCC or
metastatic neuroendocrine tumors (38,43,88). Transarterial embolization without chemotherapy
consists of embolization of the arteries feeding the tumor, which results in ischemia within the
tumor and subsequent tumor necrosis (Fig. 34-20).
FIGURE 34-17. Hypersplenism in a 41-year-old man with cirrhosis secondary to hepatitis
B. A: Pre-embolization contrast-enhanced computed tomography shows homogeneous
splenomegaly (S) of 22 cm in long axis. B: Initial digital subtraction angiography obtained
after selective injection into the celiac artery shows an enlarged splenic artery with
increased flow. C: Selective injection is performed into the inferior terminal branch of the
splenic artery. D: Final digital subtraction angiography obtained after partial splenic
embolization using 700- to 900-m Tris-acryl microspheres (Embospheres) shows reduced
flow and occlusion of intrasplenic arteries. E: Postembolization contrast-enhanced
computed tomography obtained 2 weeks after embolization shows areas of splenic
devascularization (S). The patient had a significant effect, with an increased platelet count.
(Case courtesy of Olivier Seror, M.D., Bondy, France.)
FIGURE 34-18. Chemoembolization of HCC in a 56-year-old man. A: Pre-embolization
contrast-enhanced computed tomography (coronal maximum-intensity projection
reconstruction) shows a large hypervascular HCC of segment VIII (star). An enlarged
feeding artery is identified (arrowhead). B: Initial digital subtraction angiography (arterial
phase) obtained after selective injection into an enlarged arterial branch supplying blood
supply to the HCC. C: Initial digital subtraction angiography (late phase) obtained after
selective injection into an enlarged arterial branch shows the hypervasculrized HCC.
Chemoembolization was performed using 60 mg of epirubicin, 10 mL of lipiodol, and gelatin
sponge pledgets. D: Postembolization computed tomography obtained 3 months after
chemoembolization shows aggregation of lipiodol within the devascularized tumor (29%
reduction in volume).
Arterial Chemoembolization and Embolization for

Hepatocellular Carcinoma
Intravenous antibiotic prophylaxis is usually administered at the time of embolization (87).
Sedation is provided according to the local protocol. A flush aortogram via a pigtail catheter
placed at the level of the celiac artery is not necessary if preprocedural multiplanar vascular
reconstructions have been obtained using MDCT or MRI (Table 34-4) (89). A selective
arteriogram of the superior mesenteric artery using a 5-Fr catheter is performed to identify a
right hepatic artery and prolonged angiogram is then carried out in the venous phase to identify
portal vein thrombosis. Again, if the portal vein is proven patent on recent MRI or CT, this
angiographic evaluation can be skipped (89). Then the celiac artery is selected using the same
catheter and a selective arteriogram is performed to identify tumoral blush (Figs. 34-18 and 34-
19). Though one wants to be as selective as possible to avoid chemoembolizing normal liver,
being too selective may result in parts of the tumor not being treated. In general, either the right
or the left main hepatic artery is the optimal position for the catheter (Fig. 34-19). In cases
where there is tumor in both lobes, the one showing more tumoral blush during the diagnostic
arteriogram should
be targeted first (Fig. 34-19). If the 5-Fr catheter cannot be advanced to the desired location
because of unfavorable anatomy, a 2.7- to 3-Fr microcatheter over a 0.016- to 0.021-in. guide
wire can be used coaxially (Table 34-4). If one is targeting a peripheral solitary lesion, then
superselective catheterization can be attempted (Fig. 34-20). There are many potential
variations of the anatomy of the arterial supply to the liver. Scrupulous attention to hepatic
arterial anatomy, variants, and nontarget branches is necessary to avoid potentially serious
complications. In addition, HCC can create a sump effect, reversing the flow in the
gastroduodenal artery. Thus a superior mesenteric artery injection may fill the hepatic artery via
an enlarged gastroduodenal artery, which could be mistaken for a replaced right hepatic artery.
Some large or superficial nodules may parasitize arterial supply from the arteries of adjacent
organs, especially after multiple prior embolization procedures (90). Such parasitization may
require embolization of arterial branches arising from the right renal, colonic, gastric, inferior
phrenic, internal thoracic, and intercostal arteries (90). Failure to identify additional supply to
HCC may be associated with treatment failure (90). It is also important to recognize that not all
such parasitized arteries can be safely treated without risk to other important organs (90).
FIGURE 34-19. Chemoembolization of HCC in a 61-year-old man. A: Pre-embolization
contrast-enhanced computed tomography (arterial phase) shows a large hypervascular
HCC involving the whole right lobe. B: Initial digital subtraction angiography (arterial phase)
obtained after selective injection into the proper hepatic artery shows a large
hypervascular tumor (T). C: Chemoembolization was performed using 80 mg of epirubicin,
10 mL of lipiodol, and 300- to 500-m Tris-acryl microspheres (Embospheres).
Postembolization subtraction angiography obtained after selective injection into the
common hepatic artery shows complete tumoral devascularization sparing arterial
branches to the left part of the liver. D: Postembolization computed tomography obtained 3
months after chemoembolization shows devascularization of the tumor and a marked
reduction in volume, 59%. The patient underwent successful right hepatectomy and made a
full recovery.
FIGURE 34-20. Arterial embolization of HCC in a 47-year-old man. A: Pre-embolization
contrast-enhanced computed tomography shows a large hypervascular HCC of the right
liver lobe. B: Initial digital subtraction angiography (arterial phase) obtained after selective
injection into the proper hepatic artery shows a large hypervascular tumor. C:
Superselective catheterization of the arterial tumoral feeding arteries using a 2.7-Fr
microcatheter shows a hypervascularized mass. D: Arterial embolization without
chemotherapy was performed using 53- to 106-m Hepaspheres, superasborbent polymer
microspheres. Postembolization digital subtraction angiography obtained after selective
injection into the proper hepatic artery shows targeted tumoral devascularization. E:
Postembolization contrast-enhanced computed tomography obtained 1 month after
embolization shows complete devascularization of the tumor. (Case courtesy of Keigo
Osuga, M.D., Osaka, Japan.)
TABLE 34-4 EMBOLIC MATERIALS AND CATHETERS USED FOR LIVER

ARTERIAL EMBOLIZATION OR CHEMOEMBOLIZATION

Pigtail catheter, 5 Fr
Terumo
Selective SMAa and celiac

catheterization
C2 Cobra visceral, 5 Fr Cook, Merit Medical, Terumo
Simmons 1 catheter, 5 Fr Merit Medical, Terumo
Embolization agents
Biosphere Medical
microspheres
a Superior mesenteric artery.
During the initial angiographic evaluation, the interventional radiologist may observe
arteriovenous shunting through the tumor. If TACE is performed, the risk of nontarget
embolization (lungs, since the most common type of shunting is hepatic artery to hepatic vein) is
high (Fig. 34-21). Instead, the operator should generally proceed with bland embolization using
gelatin sponge pledgets or large calibrated microspheres until the shunting resolves (Table 34-
4) (Fig. 34-21). If at the end of embolization the tumor is still enhanced by contrast, then TACE
may be performed. Otherwise, no additional treatment should be performed and the patient
should be re-evaluated after 2 to 4 weeks (87).
When no arteriovenous shunting is visible, TACE is performed slowly by hand-injection under
fluoroscopy to ensure that there is no reflux of chemotherapy agent back around the catheter
that may result in nontarget embolization. Inadvertent embolization of the gastroduodenal artery
can have serious consequences including gastric or duodenal necrosis.
Single-, double-, or triple-agent chemotherapy mixtures are used with varying frequency. Triple
chemotherapy mixtures composed of 100 mg cisplatin, 10 mg mitomycin C, and 50 mg
doxorubicin hydrochloride (Adriamycin) have been used extensively (87). Other groups may
consider only one agent such as cisplatin (70 to 100 mg), doxorubicin (dose adjusted to bilirubin
concentration, for instance, 75 mg/m2 body surface area, for normal bilirubin levels), or, more
recently, epirubicin (50mg/m2) (Figs. 34-18 and 34-19) (6,87). Currently there are no data as to
the relative efficacy of specific chemotherapy mixtures. The chemotherapy is usually mixed 1:1
with lipiodol. Chemotherapy and lipiodol-resistant three-way stopcocks should be used to obtain
the emulsion (87).
Additional embolization with 150- to 300-m PVA particles or gelatin sponge slurry or pledgets
until the flow in the treated artery is reduced further increases the chemotherapy residence time
within the tumor (Fig. 34-19, Table 34-4) (6,87). Recently promoted approaches include
administration of spherical particles such as Tris-acryl microspheres (Embosphere; Biosphere
Medical), the optimal diameter of which remains a matter of debate (usually 100 to 500 m)
(Fig. 34-18, Table 34-4) (87,88).
At the end of the procedure, a high-resolution spot radiograph of the liver should be obtained to
document distribution of lipiodol (Fig. 34-18). Routine nursing checks and care are adequate
thereafter. A morphine or fentanyl PCA pump should be used for pain control and anti-emetic
drugs should be given. Hydration is critical to reduce the consequences of a possible tumor
lysis syndrome such as acute renal failure.
The alternative strategy consists in performing arterial embolization ideally with a superselective
approach. It has been demonstrated that the use of large volumes of lipiodol, in particular, in
association with chemotherapy may cause hepatic parenchymal damage and bile duct
ischemia. Therefore, arterial embolization using small calibrated microspheres such as Tris-
acryl microspheres (Embosphere; Biosphere Medical) or superabsorbent polymer
microspheres (Hepasphere; Biosphere Medical) has been reported to be effective (Table 34-4)
(43,87,91). The diameters used vary between 40 to 50 and 300 m in the published series
(43,87,91). Obviously, smaller sizes (<100 m) may not be used in the case of HCC with
arteriovenous shunts because of the risk of pulmonary embolism (91).
Results
For maximum benefit, patients should be seen at regular intervals. When lipiodol is mixed with
chemotherapy, a noncontrast CT scan of the abdomen is usually obtained within 4 weeks
following chemoembolization to document the distribution of lipiodol and the degree to which the
tumor has taken up the chemoembolization mixture (Fig. 34-18) (89). It is generally considered
that uniform lipiodol uptake by the tumor correlates with a higher degree of necrosis compared
to spotty or lack of lipiodol uptake (87,89). Likewise, regions with high lipiodol uptake post-
TACE correlate with a higher degree of necrosis on follow-up imaging examinations. After
TACE or transarterial embolization, a contrast-enhanced CT or MRI of the liver is usually
obtained at 2 and 3 months and compared to the baseline or previous examinations (89). Tumor
necrosis is quantified based on contrast enhancement. In addition, tumor volume reduction
should also be calculated (89). If no residual viable tumor is noted, no additional TACE is
performed. Lack of satisfactory response after one TACE does not predict eventual response,
and additional TACE can be performed. The emergence of any contraindications to TACE
between successive IACE treatments may preclude repeat treatment. In some cases where
the patient was initially precluded from undergoing surgery based on tumor size, adequate
reduction in size following TACE may render the patient operable (Fig. 34-19). TACE is one of
the most popular procedures available and one that has rapidly gained favor worldwide (6,87).
Despite the fact that it has been used for many years, there has been, until recently, a lack of
prospective randomized trials regarding its efficacy (6). Because of this, the procedure
generated considerable discussion and there is currently no consensus opinion on the technique
that should be used. However, one randomized controlled trial and a recent meta-analysis
concluded that TACE was associated with improved survival of patients with nonresectable
HCC compared to nonactive treatment. The Barcelona group performed a prospective
randomized trial that recorded 1-, 2-, and 3-year survival of 82%, 63%, and 29, respectively,
for patients undergoing TACE, versus 63%, 27%, and 17% for untreated patients (92). The trial
was even terminated early when the significant survival benefit of the TACE group became
obvious (92). A meta-analysis of published randomized controlled trials looking at the 2-year
survival of patients with unresectable HCC who underwent TACE, transarterial chemotherapy,
or transarterial embolization versus nonactive treatment was recently presented (93). Patients
who underwent transarterial treatments had significantly improved survival, with an odds ratio of
0.54. The TACE and transarterial embolization groups had an odds ratio of 0.45, and the
transarterial chemotherapy group an odds ratio of 0.65 (93).
FIGURE 34-21. Arterial embolization in a 38-year-old man with HCC secondary to hepatitis
C. A: Initial digital subtraction angiography (arterial phase) obtained after selective injection
into the proper hepatic artery shows a diffuse hypervascularization. B: Initial digital
subtraction angiography (late phase) obtained after selective injection into the proper
hepatic artery shows multiple large intrahepatic arterioportal shunts. C: Arterial
embolization without chemotherapy is performed using 700- to 900-m Tris-acryl
microspheres (Embospheres) to achieve arterial occlusion while avoiding nontarget portal
embolization.
Serious complications following arterial embolization or TACE for HCC are uncommon with
careful patient selection, thorough preprocedural preparation, and meticulous embolization
technique (87). Postembolization syndrome occurs in most patients and can last for 1 to 2
weeks. Secondary infection of the necrotic liver/tumor can occur and may lead to the formation
of liver abscess, which may require percutaneous drainage. Previous biliary tract surgery such
as enterobiliary anastomosis or sphincterotomy is associated with a greater incidence of liver
abscess, and this is likely due to the colonization of the biliary tree by gut organisms (94).
Arterial Chemoembolization and Embolization for Liver

Metastases
Metastatic colon cancer to the liver has proven to be less responsive than hoped for to TACE,
with a reported median survival of 10 to 12 months. Other metastatic neoplasms to the liver
that are amenable to arterial embolization or TACE include neuroendocrine, breast cancer,
adrenal cancer, and sarcomas. Though technically feasible for all types of metastases, TACE
appears to be more effective in tumors, which are highly vascular. The use of radioembolization
using yttrium-90 has recently been investigated for neuroendocrine liver metastases, particularly
responsive to TACE or embolization, and for less vascular nodules such as colorectal
metastases to the liver (38,46).
Islet cell neoplasms arising from the pancreas (endocrine pancreatic tumors) and carcinoid
tumors are rare neuroendocrine tumors that represent <5% of all primary gastrointestinal
malignancies (95). Most patients with neuroendocrine gastrointestinal tumors present with
disseminated disease and involvement of the liver at the time of diagnosis. It has been
estimated that 50% to 95% of patients with neuroendocrine tumors may develop liver
metastases (95,96). Liver metastases of endocrine tumors are of major prognostic significance
and >80% of patients with advanced liver disease will die within 5 years of diagnosis (96). The
spectrum of clinical presentation includes patients with progressive liver disease or with
exacerbated extreme clinical syndromes secondary to aberrant hormone secretion (96).
Symptoms related to the secretion of hormonal substances include carcinoid syndrome with
flush and diarrhea or symptoms associated with endocrine pancreatic tumor such as
hypoglycemia, multiple ulcers, skin rash, and diabetes (95,96). Since the introduction of
somatostatin analogues, progressive liver disease has replaced hormone excess as the leading
cause of mortality (96,97). The aims of treatment
include alleviation of hormonal syndromes or pain symptoms refractory to medical management
and control of progressive tumor growth (38). Hepatic resection is rarely feasible because of
the extension of the disease at the time of diagnosis (97). Systemic chemotherapy using 5-
fluorouracil, doxorubicin, or streptozocin produces biochemical and/or tumoral responses in
50% of endocrine pancreatic tumors but midgut carcinoid tumors are usually resistant to this
treatment (98). Because hepatic metastases from neuroendocrine tumors are usually
hypervascular, this provides a good rationale for considering arterial embolization or arterial
chemoembolization as a therapeutic measure (99, 100, 101, 102, 103).
Eligibility requirements for hepatic artery embolization or TACE for neuroendocrine tumor
metastases include adequate hepatic and renal function, acceptable coagulation parameters,
and hepatopedal portal venous flow (38). To decrease the risk of carcinoid crisis in those
patients with symptomatically active tumors, 150 to 500 g of somatostatin should be given the
day before embolization and continued for 3 to 5 days posttreatment. While what constitutes an
adequate amount of residual uninvolved liver is not clear, in most published series 50% to 60%
tumor replacement is considered as the acceptable upper limit. It is well recognized that >75%
tumor replacement is associated with a higher incidence of hepatic failure postembolization
(101). In patients with borderline liver and/or renal function, superselective embolization using
smaller amounts of embolization agent without chemotherapy could be considered (Fig. 34-22).
There is no consensus opinion on the best embolotherapy protocol (38). A variety of methods
has been used, and no prospective comparative studies have been conducted: bland arterial
embolization without chemotherapy using regular PVA particles, Tris-acryl microspheres, or
gelatin sponge pledgets or chemoembolization using a cytotoxic agent (such as doxorubicin,
mitomycin C, cisplatin, or streptozocin) and lipiodol with or without a bland embolization agent
(Figs. 34-22 and 34-23) (38,99, 100, 101, 102, 103). No study has demonstrated superiority of
adding either chemotherapeutic agents or lipiodol for the treatment of neuroendocrine hepatic
metastases or that these agents may increase the risk of severe complications (101). For
patients with extensive liver involvement, only one lobe of the liver should be treated during each
session to minimize the risk of postembolization liver failure. For bland embolization, regular
PVA particles or Tris-acryl microspheres 100 to 500 m in diameter are usually favored,
switching to larger particles when arteriographic tumor blush decreases and terminating
embolization when there is flow stasis throughout the targeted artery distribution (Fig. 34-22)
(38,101). For chemoembolization, the most widely used agent is doxorubicin (50 mg/m2 body
surface area) mixed with lipiodol. Following intra-arterial chemotherapeutic injection, it is usual
to occlude the feeding arteries with PVA particles or gelatin sponge pledgets (38).
FIGURE 34-22. Liver metastases involving only the right lateral segment secondary to ileal
neuroendocrine tumor in a 45-year-old man. A: Initial digital subtraction angiography
(arterial phase) obtained after selective injection into the proper hepatic artery shows a
single hypervascular nodule (M). B: Superselective catheterization of the feeding artery is
performed with the use of a 2.7-Fr microcatheter and confirms the hypervascular
characteristics of the nodule. C: After selective embolization using 6 mL of Tris-acryl
microspheres (300 to 500 m in diameter), targeted devascularization of the nodule is
seen.
FIGURE 34-23. Multiple liver metastases secondary to renal neuroendocrine tumor in a 55-
year-old woman. A: Pre-embolization contrast-enhanced computed tomography shows
multiple hypervascular liver nodules (arrows). B: Initial digital subtraction angiography
(arterial phase) obtained after selective injection into the celiac artery shows a middle (M)
and a left (L) hepatic artery. C: Initial digital subtraction angiography (late phase) obtained
after selective injection into the celiac artery shows multiple hypervascular nodules involving
both lobes of the liver. Chemoembolization is performed using 1.5 g of streptozocin, 7.5 mL
of lipiodol, and 6 mL of Tris-acryl microspheres (Embospheres). D: Two thirds of the
mixture was injected into the middle hepatic artery, which is occluded after treatment. E:
One third of the mixture was injected after superselective catheterization of the left hepatic
artery.
Results
All results for embolotherapy (embolization or TACE) published so far are case series involving
small numbers of subjects with a wide range of disease severity. Despite this, allowing for
different stages of disease and method of treatments, these series show the good clinical
response rate (reduction of symptoms, somatostatin requirement, tumor size) of between 50%
and 100%, with symptom-free intervals of 6 to 12 months in 90% to 100% of patients (99, 100,
101, 102, 103). Interestingly, the reported 5-year survival of 53% to 83% postembolotherapy is
superior in comparison to historical controls receiving medical treatment alone (0% to 40%).
More recently, it has been suggested that chemoembolization using streptozocin may be the
most effective regimen to obtain biochemical, clinical, and tumoral response (Fig. 34-23) (102).
Most published series reported good symptomatic palliation, with response rates ranging from
75% to 100%, following all of the above embolization protocols (99, 100, 101, 102, 103).
FIGURE 34-24. Multiple liver metastases secondary to colorectal carcinoma in a 53-year-

old woman. A: Initial contrast-enhanced computed tomography shows a large mass
involving the right liver lobe and extending to segment IV. B: Coronal reconstruction of the
same contrast-enhanced computed tomography shows a small left liver lobe. C: Volumetric
evaluation is performed: total liver volume is 2,565 cm3. D: Volumetric evaluation of the
future liver remnant is 503 cm3, which corresponds to 20%. The decision to perform a right
portal vein embolization is made before right hepatectomy extending to segment IV. E:
Portography obtained using a peripheral left portal venous approach demonstrates the
segmental anatomy. F: Right portal vein embolization is performed using acrylic glue
(digital subtraction angiography). G: Plain abdominal film shows embolized portal branches
filled with radiopaque lipiodol mixed with acrylic glue.
Serious complications following embolization of metastatic neuroendocrine tumor are

uncommon with careful patient selection, thorough preprocedural preparation, and meticulous
angiographic technique (38). Reported major complication rates and death rates after
embolotherapy for neuroendocrine tumor hepatic metastases range from 1% to 10%, and 0%
to 3%, respectively. Postembolization syndrome occurs in practically all patients and can last
for 1 to 2 weeks. Until the introduction of somatostatin analogues, exacerbation of the
symptoms of carcinoid or frank carcinoid crisis was common with embolization of carcinoid
metastases. Now, with somatostatin analogues used routinely for hormonally active tumors,
both during and after embolization, carcinoid crisis occurs in only a small percentage of
patients.
Portal Vein Embolization

PVE is increasingly used for preoperative treatment in patients scheduled to undergo liver
resection when the volume of the future remnant liver appears to be insufficient (Fig. 34-24) (8).
If PVE is not performed, these patients are at risk of life-threatening postoperative liver failure
(8). The possibilities of curative resection of liver tumors are mainly limited by the volume of the
future remnant liver (50). It is generally accepted that the minimal volume of the future remnant
liver required for a normal liver is at least 25% that of the initial liver (8,50). This percentage
should be substantially greater (>30%) in patients with chronic liver disease and in those
already treated with chemotherapy because of a more limited capacity of hypertrophy (8). The
objective is to embolize the portal vein branches feeding the abnormal segments to be
resected. PVE enables portal flow redistribution to the branches of the future remnant liver
(50). This portal flow, which is rich in hepatotrophic substances, induces hypertrophy of the
nonembolized segments of the future remnant liver, particularly in patients without underlying
chronic liver disease, allowing the planned resection to be performed. In clinical practice, for
instance, an extended right hepatectomy is hardly feasible without PVE because the left lobe is
small. Preoperative PVE was first reported in Japan in 1986 in patients with HCC, with the
double goal to induce hypertrophy of the future remnant liver and to prevent retrograde
intraportal tumoral dissemination (104). A few years later, PVE was offered to patients with
hilar cholangiocarcinoma and liver metastases to extend the indications for curative surgery (8).
The procedure may be performed under conscious sedation and analgesia but most groups
favor the use of general anesthesia, which provides more comfort for the patient and for the
interventional radiologist (50). When the objective of PVE is to occlude right branches, the
preferred access is the anterior subxiphoid left route to get access to the peripheral portal
branch of segment III or the Rex recess (50). This approach provides antegrade catheterization
of all right branches and free-flow embolization (Table 34-4). The puncture is performed under
sonographic guidance. When branches for segment IV have to be occluded, it is possible to
enter the segment III branch to facilitate catheterization of segment IV branches. Some authors
recommend the ipsilateral approach (right portal vein branches for right PVE) to avoid
inadvertent lesions due left
lobe branches. However, this technique requires the use of a double- or triple-lumen catheter to
avoid reflux of embolization materials. In all cases, retrograde catheterization of the portal vein
to perform pre-embolization portography is mandatory to identify individual branches and
anatomical variations. Catheterization and distal embolization of every branch to be embolized
are performed using a 5-Fr catheter (Table 34-5) (50). The degree of selectivity
(subsegmental, segmental, or sectorial) depends on the individual anatomy and flow. The ideal
location of the catheter tip should allow free-flow embolization without risk of inadvertent reflux
of embolization material. Special caution should be exercised when embolizing segment IV
branches to avoid nontarget embolization of left lobe veins (39).
TABLE 34-5 EMBOLIC MATERIALS AND CATHETERS USED FOR PORTAL

VEIN EMBOLIZATION
Portal vein catheterization
5-Fr needle catheter Cook
Simmons 1 or 2 catheter, 5 Fr Cook, Merit Medical, Terumo
Embolization agents
Embosphere, Tris-acryl microspheres Biosphere Medical
Ethanol Cura Medical, Ethicon
Lipiodol ultrafluid Guerbet
There is currently no consensus opinion regarding the embolization material used to perform
PVE. Most authors will favor the use of a mixture of acrylic glue (cyanoacrylate) and lipiodol
(Fig. 34-24, Table 34-5) (50). This mixture allows complete and durable cross-sectional
vascular occlusion. The radiopacity of the mixture may increase the level of safety at the time of
embolization. The recommended ratio of cyanoacrylate to lipiodol is 1:2 or even 1:3, to delay
the polymerization time and allow a more distal occlusion. A total dose of 1 to 6 mL of
cyanoacrylate administered in successive injections of mixture is usual for the procedure (Fig.
34-24). After glue injection, the catheter should be flushed with isotonic glucose or cleaned
using the 0.035 guide wire to prevent catheter occlusion. Gelatin sponge pledgets or slurry has
been employed for PVE because it is easy to deliver and very cheap (50). Ethanol injections
with a total volume of 15 to 50 mL have been successfully proposed for PVE (Table 34-5) (53).
Even if easy to deliver, this product may require the use of the balloon occlusion technique and
may have a negative impact on the liver function (50,53). More recent studies have emphasized
the ability of regular PVA particles or Tris-acryl microspheres to achieve targeted portal vein
devascularization and significant induced hypertrophy (Table 34-5) (39,105). A more proximal
embolization using coils should be avoided because hypertrophy of the remaining liver may be
minimal (50). However, coils may be used as a secondary embolization agent in combination
with particles (39).
Results
The first factor to be considered in determining whether PVE is indicated is the presence or
absence of underlying liver disease. A normal liver has a greater regenerative capacity than a
cirrhotic liver, functions more efficiently, and tolerates injury better. Survival after resection
beyond 60% of the functional parenchyma in patients with cirrhosis is unlikely (50). In patients
with chronic liver disease (chronic hepatitis, fibrosis, or cirrhosis), the increase in nonembolized
liver volumes after PVE varies from 28% to 46%, and hypertrophy after PVE may take more
than the usual 4 weeks because of slower regeneration rates (50,53). The degree of
parenchymal fibrosis is thought to limit regeneration, possibly as a result of reduced portal
blood flow (106).
Curative resection of liver metastases is mainly performed in patients presenting with colorectal
primary cancer. At the time of diagnosis, the majority of patients presents with unresectable
metastases and resection can be performed in 20% of them (8). PVE may therefore
dramatically increase the number of surgical candidates by increasing the volume and the
function of the future remnant liver (50). For instance, in patients without cirrhosis who have
cholangiocarcinoma or liver metastases, resection of the right liver plus segments IV and/or I
(i.e., extended right hepatectomy) or, less often, the left liver plus segments V/VIII and/or I
(i.e., extended left hepatectomy) is often indicated (50). In the former case, as a result of the
high incidence of small-volume left lateral bisegment (II and III) in the absence of compensatory
hypertrophy, preoperative PVE is frequently needed (50). Elias et al. demonstrated that
patients considered to have unresectable tumors as a result of inadequate liver volume at
presentation could undergo complete resection after treatment with PVE, with an associated 5-
year overall survival rate of 29% (107). Azoulay et al. found that the 5-year overall survival rate
after resection in patients who required PVE was similar to that in patients who did not have
PVE (106).
PVE has clearly been shown to enable safer resection with acceptable oncologic outcomes in
properly selected patients with otherwise normal livers. Clinical tolerance of PVE is generally
good, with only mild abdominal discomfort and fever lasting <7 days. In a large series of 188
patients undergoing PVE, the complication rate was 13%, associating clinical manifestations in
only 7% and incidental imaging findings (i.e., migration of small emboli in nontargeted branches)
in the remaining 6% (108). Thrombosis or nontarget embolization of the portal branch feeding
the future remnant liver occurred in 3% of patients (108). The complication rates after PVE are
higher in patients with chronic liver disease than in those with an otherwise normal liver because
of the increased risk of secondary portal vein thrombosis, presumably from slow flow in the
portal vein trunk after PVE (108).
UTERINE FIBROID EMBOLIZATION

Introduction
Since the first reports of its use in the 1970s as a therapeutic option for women with life-
threatening postpartum bleeding or inoperable neoplasm, uterine artery embolization has
become increasingly accepted as therapy to treat symptomatic uterine fibroids
(3,4,24,11,48,108, 109, 110). Leiomyomata, commonly known as fibroids, are benign
neoplasms derived from the smooth muscle of the uterus and are believed to arise from a
single myometrial cell (10). They are among the most common lesions of the female genital
tract and occur in 20% to
25% of women of reproductive age and are more common in women of Afro-Caribbean origin
than white women (10). After menopause lack of hormonal stimulation causes the fibroids to
regress, they may undergo infarction as a result of ischemia and may calcify (10). Although
most fibroids are asymptomatic, some cause symptoms due to their position or their size. They
are one of the main causes of menorrhagia and may also cause compression of adjacent
organs, with constipation, bloating, backache, and urinary frequency (10). Fibroids may occur
at any age after menarche but are particularly common in women in their 40s (10).
Progestatives or hormone suppressants are often used at the initial stage in the management
of symptomatic fibroids (10). Hormone suppressant therapy, in the form of gonadotropin
releasing hormone agonists is effective in ~50% of patients; the effect is temporary, however,
and the fibroids will regrow within a few months of the drug being discontinued (10).
Conventional treatment of fibroids has been surgical, i.e., hysterectomy or myomectomy
(10,111, 112, 113, 114). In recent years the surgical armamentarium has been expanded with
further procedures such as laparoscopic myomectomy and hysteroscopic resection of
submucous myomas (112,113). The major drawback associated with myomectomy is the risk
of recurrence requiring further surgery, which has been estimated as between 20% and 50% at
5 years (10). It is important that any radiologist embarking on UFE has a good working
knowledge of surgical procedures for fibroids, their efficacy, and their complications. With the
increasing frequency of use of UFE, a greater understanding of both the advantages and the
potential risks of this procedure has occurred and the scientific evidence has also greatly
improved. The technique has been significantly modified; the postprocedural imaging evaluation
has changed dramatically during the last years. Evaluation of results associated with UFE has
included clinical success rate and uterine/fibroid volume reduction. Cost, recovery time, change
in quality of life, and patient acceptance are other important considerations. The associated
risks of complications associated with UFE are of paramount importance before offering this
procedure to young women interested in future fertility. UFE is a highly effective, minimally
invasive alternative to surgery and is now widely accepted for the management of fibroid-
related symptoms.
FIGURE 34-25. A 39-year-old woman with multiple uterine fibroids. A: Digital subtraction
angiography of selective injection into an enlarged left uterine artery demonstrates diffuse
uterine hypervascularization consistent with fibroids. B: After embolization to stasis using 3
vials of nonspherical 355- to 500-m regular PVA particles, the left uterine artery is
completely occluded.
The method of UFE has been extensively described in the literature (48,109,110,115). In
essence it involves the placement of a catheter into the uterine arteries and injection of
embolization particles into the uterine arteries to obtain fibroid infarction and shrinkage. There
are some differences in technique between centers, some catheterizing the uterine arteries
directly with 4- or 5-Fr catheters, while others use microcatheters (Figs. 34-25 and 34-26,
Table 34-6) (48,109,110,115). Microcatheters may lead to a more effective devascularization of
all uterine fibroids than large, 4- or 5-Fr catheters, thanks to a reduced incidence of flow-limiting
arterial spasm (Fig. 34-26). When considering the choice of an embolization agent, the physical
properties (granulometric distribution, compressibility) and the method of delivery should be
considered (Fig. 34-9) (15). Nonspherical PVA particles were the first embolization agents used
for UFE (Fig. 34-25) (Table 34-6) (11,15,23,31,48,109,110). Spherical embolization particles,
such as Tris-acryl microspheres, have been developed to address some of the disadvantages
of nonspherical particles such as the unpredictable level of arterial occlusion and clumping
associated with them (Fig. 34-5 and 34-6, Table 34-6) (12,116). Recently, spherical PVA
particles have also been introduced (Figs. 34-7 and 34-8, Table 34-6) (40). To date, there is no
consensus opinion on the type and size of embolization materials for UFE. In addition, the
appropriate technique of embolization
(i.e., angiographic end point) with each of the available products is still an ongoing debate.
Local anesthesia and intravenous sedation (combination of narcotics and benzodiazepines) are
used because embolization is performed with the patient undergoing conscious sedation
(48,109,110). Typically a 0.035-angled hydrophylic guide wire is used and a 4- or 5-Fr visceral
catheter is placed over the wire and used to select the contralateral iliac system
(48,109,110,115). The tip of the catheter is placed into the transverse segment of the uterine
artery, ideally distal to the origin of cervicovaginal branches, and digital subtraction angiography
is performed before embolization (Fig. 34-25) (117). After embolization of the contralateral
uterine artery, either the initial visceral Cobra or a similarly shaped catheter is used to select
the ipsilateral internal iliac artery after forming a Waltman's loop. The same procedure is then
repeated to catheterize the uterine artery.
FIGURE 34-26. A 43-year-old woman with multiple uterine fibroids. A: Digital subtraction
angiography of superselective injection into a moderately enlarged right uterine artery is
obtained using a 2.7-Fr microcatheter (A). B: After embolization to stasis using 3 mL of
700- to 900-m spherical PVA particles (Bead Block), the right uterine artery is completely
occluded.
The perifibroid vascular plexus surrounding the fibroid (with arteries ranging between 500 and
900 m in diameter) seems to be a logical target for embolization (116,117). In addition,
because of potentially dangerous pelvic anastomoses and the lack of specific tumoral feeding
arteries, small particles should not be used (116). From experimental and clinical reports, it has
been suggested that Tris-acryl microspheres >500 m should be the best compromise between
safety and efficacy (Figs. 34-10 and 34-11, Table 34-6) (12,116). Because PVA microspheres
are more compressible than Tris-acryl microspheres, the use of 700- to 900-m PVA
microspheres is currently recommended for UFE (Figs. 34-9 and 34-26). Conversely, because
of a more proximal occlusion than with microspheres, nonspherical PVA particles larger than
355 to 500 m can be used (Fig. 34-25). The use of 150- to 250-m nonspherical PVA particles
promoted in the initial studies has been abandoned because of increased complication rates
(11). Complete occlusion of the uterine artery with stasis of contrast material is the usual
angiographic end point when nonspherical PVA particles are injected (Fig. 34-25) (48).
Embolization is stopped when a standing column of contrast is present in the uterine artery or
when reflux of contrast toward the uterine artery origin or into the hypogastric artery is
observed (Fig. 34-25). When Tris-acryl microspheres are used, a limited embolization of the
uterine arteries should be performed to reduce ischemic injury to normal
myometrium/endometrium due to complete occlusion of collateral flow (Fig. 34-27) (12,116).
The curvilinear enlarged arteries of the perifibroid plexus should be occluded (116). Typically, a
pruned tree appearance is obtained on the final angiogram, with the proximal portion of the
primary trunks still patent and all distal portions occluded (Fig. 34-27) (116). This end point
usually coincides with sluggish forward flow remaining in the main uterine artery (116).
Secondary signs of embolization completion include flow redistribution with identification of
normal myometrial branches, easy reflux into the ovarian artery when it had not been present
earlier, and filling of cross-uterine vessels. When PVA microspheres are used, the
recommended angiographic end point should be stasis or near-stasis (Fig. 34-26). Radiation
exposure should be a priority consideration, particularly in young patients.
TABLE 34-6 EMBOLIC MATERIALS AND CATHETERS USED FOR

UTERINE FIBROID EMBOLIZATION

Pigtail catheter, 4 or 5 Fr
Terumo
Selective internal iliac catheterization
C2 Cobra visceral, 4 or 5 Fr Cook, Merit Medical, Terumo
Roberts catheter, 5 Fr Cook

Embocath, 3 Fr Biosphere Medical
Embolization agents
Regular PVA particles (>355 m) Boston Scientific, Cook
Embosphere, Tris-acryl microspheres

Biosphere Medical
(>500 m)
Bead Block, PVA microspheres (>700

Terumo
m)
Contour SE, PVA microspheres (>700

Boston Scientific
m)
Caps recherche, Ethicon, Rusch

Gelatin sponge
Pilling
Results
Clinical success has been measured by the degree of improvement or the frequency of
resolution of symptoms (110). In most studies, these symptoms include heavy menstrual
bleeding, pelvic pain, and bulk-related symptoms (pressure, bloating, and urinary frequency). In
most of the published studies, regular PVA particles were used as the embolization agent
(11,48,109,110). Success rates for treating menorrhagia, pelvic pain, and bulk-related
symptoms ranged from 81% to 96%, 70% to 100%, and 46% to 100%, respectively
(11,48,109,110). Three prospective studies with more than 200 patients enrolled have been
published recently in the gynecological literature (48,109,110). From a cohort of 508 patients
undergoing UFE using regular PVA particles in Canada, significant improvements were reported
for menorrhagia (83%), dysmenorrhea (77%), and urinary frequency (86%) at 3 months (110).
Menorrhagia was significantly improved, with a reduction in the mean menstrual duration from
7.6 to 5.4 days (110). Walker and Pelage reported on their experience with UFE in 400 women
with symptomatic fibroids with a mean clinical follow-up of 17 months (48). Menstrual bleeding
improved in 84% of women and pelvic pain improved in 79%. In the short term, UFE using
gelatin sponge pledgets alone seems to show results comparable to those obtained with PVA
particles (118). Katsumori et al. reported improvement in menorrhagia and in bulk-related
symptoms in 98% and 97% of cases, respectively, at 4 months after embolization (118).
FIGURE 34-27. A 31-year-old woman with multiple intramural uterine fibroids. A: Bilateral
simultaneous injection into the uterine arteries shows diffuse uterine hypervascularization.
B: After bilateral simultaneous limited embolization of the uterine arteries using a total of 7
mL of 500- to 700-m Tris-acryl microspheres (Embospheres), no residual vascularization
to the fibroids is visible. Note that both uterine arteries and normal myometrial branches
are patent.
The initial experience with the use of Tris-acryl microspheres mirrors the results obtained with
regular PVA particles (12,116). Spies et al. reported a significant reduction of menstrual
bleeding and pelvic pain in 92% of treated patients at 3 months (12). Pelage et al. reported
complete resolution of menorrhagia in 85% of patients with a mean follow-up of 30 months
(116). In a recent randomized study comparing Tris-acryl microspheres and PVA particles for
UFE, Spies et al. demonstrated no significant difference between the two types of embolization
particles in any of the outcome variables (119).
The recurrence rate after UFE has been reported to be <10%, most cases being related to
regrowth of fibroids not infarcted after the initial procedure (120). The long-term rate of
recurrence due to the growth of new fibroids is still to be determined (121).
Uterine volume reduction and fibroid shrinkage are evaluated after embolization as part of
imaging outcome (Figs. 34-28 and 34-29). Within 3 to 6 months after UFE, a 25% to 60%
reduction of uterine volume has been reported (48,109,110). The reduction in volume of the
dominant fibroid ranges between 33% and 68% at 3 to 12 months (48,109,110). Similar
fibroid volume reductions have been reported with the use of gelatin sponge or Tris-acryl
microspheres (118).
FIGURE 34-28. A 45-year-old woman with multiple intramural uterine fibroids. A: Pre-
embolization sagittal contrast-enhanced MRI shows a retroverted uterus with multiple
hypervascular fibroids. B: Digital subtraction angiography after selective injection into the
right uterine artery demonstrates diffuse hypervascularization. C: Digital subtraction
angiography after selective injection into the left uterine artery also demonstrates diffuse
hypervascularization. D: Embolization to stasis was achieved using 6.5 mL of 700- to 900-
m spherical PVA particles (Contour SE). Postembolization sagittal contrast-enhanced MRI
performed 24 hours after embolization demonstrates satisfactory devascularization of all
identified fibroids, with a normal myometrial perfusion.
Because the technical goal of UFE is to cause complete infarction of all identified fibroids, it is
important to assess after embolization the frequency with which the infarction occurs (121).
Complete devascularization of all fibroids is the necessary precursor of symptom improvement
in the long term (Fig. 34-28) (121). This has been demonstrated when viewing the long-term
imaging outcome of embolization, because complete fibroid infarction does result in long-term
improvement of symptoms, whereas incomplete infarction may predispose to regrowth and
clinical recurrence (121).
Complications associated with UFE can be classified as minor or major based on their severity
evaluated by the level of care required, the interventions necessary, and the final outcome (23).
Two different systems (from the Society of Interventional Radiology [SIR] and the American
College of Obstetrics and Gynecology [ACOG]) developed to allow standardized reporting of
complication severity have been used to precisely assess complications following UFE (23). In
a cohort of 400 women, the periprocedural morbidity was 8.5% according to the SIR
classification system and 5% according to the ACOG system (23). Five major complications
(1.25%) were reported in this group of patients. There was only one hysterectomy
(0.25%) complication in this study (23). In the Canadian trial, the overall complication rate after
UFE was 8% (123).
FIGURE 34-29. A 38-year-old woman with bulk-related symptoms. A: Pre-embolization

sagittal T2-weighted MRI shows a large pedunculated subserosal fibroid (F). B: Six-
months-postembolization MRI shows a degenerative fibroid with no volume reduction. The
patient ultimately required myomectomy.
One of the potentially more serious complications of uterine artery embolization is the
occurrence of an infection after embolization. Several studies have reported cases of pelvic
sepsis after uterine artery embolization (48,124). However, when several of the largest
published series are considered in aggregate, the overall rate of significant infection after
embolization remains low and can be estimated as <1% (48,123,124). It has been suggested
that submucosal fibroids, pedunculated subserosal fibroids, or large uterine fibroids may be at
increased risk for infection after embolization (Figs. 34-29 and 34-30) (124). The severity of
this particular complication was made clear by publication of the report of the first death due to
infection, in a 51-year-old patient who underwent uterine artery embolization to treat abnormal
bleeding attributed to submucosal fibroids (Fig. 34-30) (125). Most interventional radiologists
consider that large pedunculated subserosal fibroids should not reasonably be embolized. It is
often difficult to know exactly how to manage patients presenting with signs that might indicate
the presence of a uterine infection after embolization (48). The diagnosis is made even more
difficult by the fact that postembolization syndrome is often seen during the normal
postprocedure recovery period (48). In any case, a patient presenting with increasing pelvic
pain, high fever, vaginal discharge, and leukocytosis a few weeks after uterine artery
embolization should be immediately admitted for appropriate testing with imaging evaluation and
treatment (48).
FIGURE 34-30. A 40-year-old woman with a dominant intracavitary fibroid. A: Pre-

embolization sagittal T2-weighted MRI shows a large intracavitary fibroid (F). B: Six-
months-postembolization MRI shows that most of the fibroid has been expelled; a residual
part is still attached and required hysteroscopic resection.
Bilateral occlusion of the uterine arteries during uterine artery embolization clearly increases the
risk of global uterine ischemia and subsequent infarction in patients undergoing this procedure
(48,124). There have been reports of diffuse uterine ischemia and necrosis after uterine artery
embolization (124,126). The typical presentation of uterine ischemia consists of long-standing
pelvic pain, persisting for several weeks, associated with fever and an elevated white blood cell
count (48). Ultimately, these patients may require a hysterectomy for pain relief (123). While
the reported risk of uterine necrosis is 1%, steps such as avoiding complete stasis during
embolization or using large embolization particles may reduce this risk even more (116).
The onset of amenorrhea and other symptoms of menopause is a well-documented
complication following uterine artery embolization, with a reported incidence as high as 14%
(48,124,127). Symptoms commonly associated with menopause including amenorrhea, vaginal
dryness, hot flashes, mood swings, and night sweats have all been reported after uterine artery
embolization (48,124). While the incidence of this complication can still be considered low
(<4%), the impact of this complication can be quite significant, especially in patients wishing to
preserve fertility options after embolization. Small embolization particles administered within the
uterine arteries can potentially make their way into the ovarian arterial circulation through patent
uterine-to-ovarian anastomoses, increasing the risk of reduced ovarian perfusion and
subsequent ischemia (124). Microspheres <500 m in diameter can pass within the ovarian
arterial circulation after uterine artery embolization performed in sheep, which may offer some
guidance as to particle size selection for this procedure (116,117).
Ovarian ischemia may also happen after aggressive embolization of both uterine arteries when
the ovaries are supplied by the uterine arteries (117). Nevertheless, the rate of amenorrhea
depends mainly on the age of the patient at the time of treatment (127). Chrisman et al.
reported a 14% incidence of ovarian failure mainly in women over the age of 45 (127).
The first studies comparing UFE and surgery have been published recently and may help
determine the best treatment option among UFE, hysterectomy, and myomectomy for a
particular patient. Pinto et al. reported the results of a randomized clinical trial in patients
assigned to two groups: those given the option of UFE or hysterectomy and those not informed
of alternative treatment (128). The overall clinical success of UFE was 86%. The hospital stay
for patients treated with UFE was 4 days shorter than for those who underwent hysterectomy.
Of women who underwent UFE, 25% had minor complications, in contrast to 20% of those who
underwent hysterectomy having major complications (128). A recent multicenter cohort study
comparing UFE to hysterectomy has been completed by Spies et al. (129). There was no
difference between the two groups in the proportion of patients with improvement in urinary
symptoms or pelvic pressure. Similarly, no difference between groups was found in terms of
quality-of-life scores (129). The results of a controversial multicenter study comparing UFE and
hysterectomy in the Netherlands have been published (130). The overall failure and
complication rates in patients treated with UFE were higher than in patients treated with
hysterectomy (130). In addition, the results of UFE in this study were disappointing compared
to those in the available literature. The participating centers in fact had limited experience with
UFE, from both technical and clinical perspectives, which may have influenced patient outcomes
(130). The results of multicenter randomized studies comparing UFE to myomectomy should be
published soon.
Whether uterine artery embolization is a safe procedure for women desiring future fertility is still
controversial. Outcome data regarding fertility after uterine artery embolization to treat
symptoms other than infertility are still very limited. Until recently, the majority of women treated
was over the age of 40 and not interested in future pregnancy. In available prospective studies,
fecundity and delivery rates are encouraging and similar to those reported after myomectomy
(131,132). Nevertheless, in interpreting fertility rates and pregnancy outcome following UFE, it
should be taken into consideration that women undergoing UFE are not similar to the general
obstetric population. Large prospective studies, including randomized trials comparing
embolization and myomectomy in women interested in future pregnancy, may answer the
remaining questions.
CONCLUSION AND PERSPECTIVES

Arterial embolization has become a major arm of modern interventional therapy. Its applications
have become fundamental cores in multimodality treatment paradigms in oncology, urology, and
obstetrics and gynecology. Solid organ embolization, as highlighted in this chapter, for
treatment of patients with renal tumors and hypersplenism was developed in the 1970s and has
been used increasingly since then. Arterial chemoembolization is now a well-established
treatment in patients with primary or secondary liver disease. New strategies with the use of
radioactive microspheres or drug-eluting embolization particles may dramatically change the
future acceptance of chemoembolization. PVE performed preoperatively may increase the
number of surgical candidates. Initially developed in the late 1970s to treat life-threatening
postpartum hemorrhage, uterine artery embolization has become a valuable alternative to
hysterectomy and multiple myomectomy in the management of symptomatic uterine fibroids. It
may be hypothesized that, thanks to improvements in microcatheter technologies and coil
design, and the development of calibrated microspheres and drug-loaded embolization
particles, solid organ embolization will remain a first-line treatment in the management of a wide
range of conditions.
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Arterial and Venous Trauma
Chapter 35
Arterial and Venous Trauma
Hani Abujudeh
Until recently, the role of radiology in the care of trauma patients was mostly to diagnose injury
by arteriography. Today radiologists have become an integral part of a multidisciplinary trauma
patient care team. In hemodynamically stable patients nonoperative management has taken a
foothold over the past decade. Attempts to identify those patients who would fail nonoperative
management and improve the success rate have led to increased use of radiological diagnosis
and minimally invasive treatments. Computed tomography (CT) is reliable in detecting and
grading injuries and is routinely used in evaluation and triage of trauma patients to surgery or
more conservative management. Interventional radiology plays a significant role in optimizing
patient outcome after traumatic injury through the use of percutaneous transcatheter
embolization. This minimally invasive image-guided embolization technique has proven
successful in stopping hemorrhage while maximizing tissue preservation. Embolization is
sometimes preferable to surgical ligation when, for example, surgical access to the injured
blood vessel is challenging (pelvis) or the patient cannot tolerate a surgical procedure.
Embolization can also be used to stabilize the patient prior to a more extensive surgery or as a
cotreatment in a patient with complex injuries.
INTERVENTIONAL TECHNIQUES
Recent advances in technology such as digital subtraction angiography, microcatheter
techniques, steerable hydrophilic guide wires, stents (Figs. 35-1 and 35-2), and new embolic
materials have facilitated improved nonoperative management of trauma.
The major consideration of what type of embolic agent to use in trauma revolves around the
speed and the reliability of the delivery. In trauma, the two embolic agents of choice are metal
coils and gelatin sponges (Gelfoam). Metal coils integrated with a thrombogenic fibrous
material are permanent occlusive radiopaque devices, which are available in multiple shapes
and sizes. Coils can be placed fairly quickly and accurately.
Gelfoam can be administered as a slurry made by mixing the powder with contrast material to
make the material radiopaque or as pledgets. Gelfoam can be used in single or multiple
vessels. They are considered temporary occlusive agents, typically lasting 1 to 2 weeks.
APPLICATIONS
Liver
Liver injury accounts for ~5% of all trauma admissions (1). The overall mortality from liver
trauma is ~10%. As many as 80% of liver injuries stop bleeding by the time of laparotomy (2).
Recent reports indicate that minimally invasive management of liver injuries is as high as 80%
(3) and such nonoperative management of blunt hepatic trauma is considered the treatment of
choice for patients with a stable hemodynamic status.
CT has become the imaging modality of choice to evaluate the liver trauma because it is fast,
noninvasive, available, and reliable. The American Association for the Surgery of Trauma has
established a detailed classification system for liver injury, which has been widely utilized (Table
35-1). CT findings that are indicative of liver injury include periportal tracking, hemoperitoneum,
hepatic laceration, and active extravasation (4). These findings have been investigated over the
past few years as predictors for the failure of nonoperative management of liver injuries.
For example, in one study of 15 patients with liver extravasation (4) who were managed
nonoperatively, the authors classified contrast extravasation into three categories based on
location and character. Type I showed extravasation and pooling in the peritoneal cavity, Type II
had the simultaneous presence of hemoperitoneum and intraparenchymal contrast material
pooling, and Type III showed intraparenchymal contrast material without hemoperitoneum.
Nonoperative management failed in all Type I patients, who required emergency laparotomy
soon after the CT scan, and four of six Type II patients, who also required laparotomy for
hemostasis. All the Type III patients remained stable with nonoperative management (4). Of the
extravasation characteristics, the presence of contrast material in the peritoneal cavity was the
strongest predictor of nonoperative management failure (5).
Patients with active extravasation on CT may acutely decompensate and fail nonoperative
management or they may fail nonoperative management due to continuous resuscitation and
the continued need for blood products and transfusion. The presence of contrast blush on CT
demands immediate attention regardless of the grade of the injury. The trauma surgery
literature regards the detection of extravasation as a more powerful guide to the need for
intervention than the grading of organ injury.
Contrast extravasation on CT is frequently attributed to arterial bleeding (6). CT and recent CT
angiography techniques can assist in evaluation of the hepatic arterial supply and the likely
source of bleeding. To control such bleeding, transcatheter embolization is the least invasive
procedure. Thorough evaluation of the hepatic arterial supply with superselective contrast
injection, with multiple projections of the region of suspected extravasation, can increase the
sensitivity for detecting angiographic extravasation. Distal rather than proximal embolization is
preferred, as the liver is rich in collateral blood supply, and the lesion may continue to bleed if
only proximal embolization is performed. Proximal embolization also increases the risk of liver
ischemia in complex liver injuries with portal venous compromise. Gelfoam embolization or
microcoils can be used for distal embolization (Fig. 35-3). In addition to managing acute liver
injuries, embolization may prevent development of late sequelae such as pseudoaneurysms,
arteriobiliary, and arteriovenous fistulas.
FIGURE 35-1. Posttraumatic arteriovenous (AV) fistula. A: Lateral view, left lower
extremity angiogram, demonstrates a large AV fistula in the mid portion of the posterior
tibial artery. The draining vein is enlarged and opacified briskly. There is an orthopedic rod
in the tibia. B: The predeployment position of a covered stent. C: Poststent deployment
angiogram demonstrates exclusion of the AV fistula and good distal runoff. (Courtesy of
Halabi A. Kandzari, Duke University Medical Center.)
FIGURE 35-2. Inferior vena cava rupture treated with a covered stent. A: CT of the
abdomen with intravenous contrast demonstrates a leakage (arrow) from the IVC. B: Pre
(left) and post (right) stent deployment angiograms show a guide wire (circled) and active
bleeding from the iliocaval region (arrow). Final angiogram following successful stenting
confirms the absence of leakage. (Courtesy of Gabriele Piffaretti, University of Insubria,
Varese, Italy.)
TABLE 35-1 THE AMERICAN ASSOCIATION FOR THE SURGERY OF

TRAUMA'S LIVER INJURY SEVERITY GRADING SYSTEM
Grade Injury description
I Hematoma Subcapsular, nonexpanding, <10-cm surface area
Laceration Capsular tear, nonbleeding, <1 cm deep
II Hematoma Subcapsular, nonexpanding, 10%-50% surface area
Laceration Laceration, 1 to 3 cm deep
Subcapsular, >50% area or expanding, ruptures subcapsular

III Hematoma hematoma with active bleeding; intraparenchymal hematoma
>10 cm or expanding
Laceration 3 cm deep
IV Hematoma Ruptured intraparenchymal hematoma with active bleeding
Laceration Parenchymal disruption involving 25%-75% of hepatic lobe
V Laceration Parenchymal disruption >75% of hepatic lobe
Vascular Major venous injuries
VI Vascular Hepatic avulsion
Spleen
Splenic injuries used to be considered the most common of intra-abdominal injuries. These
injuries tend to be more apparent at clinical examination than liver injuries. With the adoption of
CT in abdominal trauma evaluation, and the ability to diagnose silent intra-abdominal injuries, it
has become apparent that liver injuries are more common than splenic injuries.
CT has made significant strides in improved evaluation of splenic injury. The American
Association for the Surgery of Trauma established a classification system to grade splenic
injuries (Table 35-2). However, it is difficult to prospectively predict outcome in splenic injuries
and there is only a rough correlation between the initial CT scoring of splenic injury and the
patient's clinical course or the grade of splenic injury seen at the time of surgery. A CT finding
of a contrast blush is thought to represent continuous bleeding and active extravasation (Fig.
35-4). There is increasing evidence that the presence of such a finding correlates with the
likelihood of continued or delayed bleeding from the spleen. Therefore, it is important to note
such findings when considering further management with surgery or embolization
Nonoperative management is widely accepted for hemodynamically stable patients with blunt
trauma injuries to the spleen. Initially, nonoperative management of splenic injuries was confined
to children because of the desire to preserve their immunological function. More recently,
nonoperative management has been used successfully for adult patients (7) and has also been
extended to patients over the age of 55 (8).
Unlike liver injuries, splenic injuries have a greater tendency to progress to more critical
delayed bleeding. Several hypotheses for this center on the innate fragility of the spleen
compared to the liver. Continued minor bleeding may eventually result in rupture due to
increasing pressure from an enlarging subcapsular hematoma. Another potential explanation is
remodeling of the clot. Although remodeling is a normal part of the healing process, when it
occurs in a fragile organ such as the spleen it may lead to delayed bleeding. In children, the
capsule is relatively thick compared to that in adults, and there is some evidence that the
parenchyma is also firmer in consistency. These factors may contribute to the better outcome
of nonoperative management of splenic trauma in children.
TRAUMA'S SPLENIC INJURY SEVERITY GRADING SYSTEM
I Hematoma Small subcapsular hematoma, <10% of surface area
Laceration Capsular laceration <1 cm deep
Moderate subcapsular hematoma, 10%-50% of surface area;

II Hematoma
intraparenchymal hematoma <5 cm in diameter
Capsular laceration 1 to 3 cm deep that does not involve a

Laceration
trabecular vessel
Expanding subcapsular hematoma on >50% of surface area;

III Hematoma
intraparenchymal hematoma >5 cm in diameter
Laceration Laceration >3 cm deep or involving a trabecular vessel
Laceration involving a trabecular vessel producing major

IV Laceration
devascularization (>25%)
V Laceration Completely shattered spleen
Vascular Hilar vascular injury that devascularizes the spleen
Selective use of splenic arteriography and embolization has improved the success rate of
nonoperative management of trauma patients. Early literature has shown that embolization of
splenic traumatic pseudoaneurysms improved the success rate of nonoperative management
(61% vs 25%) (9). Successful embolization can be performed by proximal splenic artery
embolization (7), superselective branch embolization (10), or a combined use of superselective
and proximal embolization (11). Two methods (proximal embolization and superselective
embolization) for splenic embolization have been described. Scalfani et al. (7) reported a
nonoperative success rate of 83% with proximal embolization of the splenic artery; this method
decreases arterial pressure in the spleen but allows continued perfusion through collateral
arteries. Superselective embolization stops active bleeding via selective occlusion of the
bleeding arterial branch or branches.
Kidney
Blunt renal trauma accounts for 85% to 90% of renal injuries, although only 4% to 25% are
significant, compared to 40% to 80% of penetrating injuries. Most traumatic renal injuries are
minor contusions or hematomas and can be managed
conservatively (10). The renal artery is injured in 7% and 4% of penetrating and blunt abdominal
trauma, respectively (12). The indication for radiologic workup in stable blunt trauma patients is
gross or microscopic hematuria. CT scanning is the preferred imaging modality and the grade
of injury can be established quickly. Management of major renal trauma is still controversial due
to the increased rate of nephrectomies in patients who undergo urgent versus delayed
exploration. Table 35-3 reports the classification scheme of The American Association for the
Surgery of Trauma to facilitate uniform management of renal injuries.
FIGURE 35-3. Coil embolization of active extravasation following blunt trauma to the liver.
A: CT scan of the abdomen with intravenous contrast demonstrates active extravasation
and pooling within the liver as well as the peritoneum. B: Hepatic angiography
demonstrating bleeding from several branches of the right hepatic artery (arrows). C:
Following embolization with microcoils, selective arteriogram demonstrates cessation of
the bleeding and isolated vessel spasm.
The renal arteries are terminal arteries. Therefore, unlike the liver, with its dual supply, and the
spleen, with its rich collaterals, acute proximal occlusion of a renal artery results in infarction
(12). However, selective and superselective distal embolization of arterial extravasation (Fig.
35-5), pseudoaneurysms, and arteriovenous fistulas is efficacious and maximizes the
preservation of renal tissue. Treatment of renal artery branch injuries is 84% to 100%
successful. A unique complication is the occurrence of temporary hypertension.
Pelvis
It is estimated that 10% to 20% of admitted trauma patients have pelvic fractures (13). CT is
increasingly used to diagnose pelvic fractures and hemorrhage, and several studies have shown
that the presence of contrast material extravasation on contrast-enhanced CT scans is a strong
predictor of arterial bleeding on angiography (14). Hemodynamic instability is noted in 10% to
20% of patients with unstable pelvic fractures. The mortality rate of this subgroup of patients is
16%, with death being secondary to exsanguinations and the late sequelae of massive
hemorrhage with prolonged shock and transfusions (15).
Urgent angiography with embolization is the most effective method for controlling ongoing
arterial bleeding in pelvic fractures (16).
The goal of embolization is to control the hemorrhage from a bleeding vessel (Fig. 35-6). Distal
embolization of pelvic arteries is preferred over proximal embolization except in cases
where the patient is unstable. Proximal embolization is used to avoid prolonging the procedure
in an actively bleeding unstable patient. Empiric embolization (without active extravasation) of
internal iliac arteries or their branches has also been successfully employed (17). Successful
embolization is frequently clinically evident, with immediate improvement in vital signs.
FIGURE 35-4. Coil embolization of active extravasation following blunt trauma to the
spleen. A: CT scan of the abdomen with intravenous contrast demonstrates active
extravasation and pooling of contrast within the spleen. B: Arteriography demonstrates
bleeding from branches (arrow) of the splenic artery. C: Splenic arteriogram after coil
embolization demonstrates cessation of the bleeding

TRAUMA'S RENAL INJURY SEVERITY GRADING SYSTEM
I Contusion Hematuria
Contained and nonexpanding subcapsular hematoma, without

Hematoma
parenchymal laceration
II Hematoma Nonexpanding, confined, perirenal hematoma

Laceration Cortical laceration <1 cm deep; no urinary extravasation
<1 cm into cortex; no collecting system rupture or urinary

III Laceration
extravasation
Parenchymal laceration extending through renal cortex, medulla,

IV Laceration
and collecting system
Vascular Main renal artery or vein injury with contained hemorrhage
V Laceration Completely shattered kidney
Vascular Avulsion of renal hilum that devascularizes the kidney
Complications of pelvic artery embolization are infrequent but include ischemia, infarction,
infection, nontarget embolization, and impotence in males. They are considered acceptable
because of the high risk of withholding such treatment.
Extremities
The extremities are the sites of injury in one third of patients with vascular trauma. Evaluation of
an extremity vascular injury should include a thorough physical examination, including exploration
of the wound to the extent possible and assessment for hard or soft clinical signs. The hard
clinical signs include extremity ischemic changes, active hemorrhage, thrill or bruit, and a pulse
deficit. The soft clinical signs include an adjacent fracture or nerve injury, a nonexpanding
hematoma, an extensive soft tissue injury, and a delayed capillary refill.
In lower extremity trauma a pulse examination should be performed and the ABI should be
determined. The incidence of vascular injury with an ABI >1 and a normal physical examination
is 9%, and all injuries are minor. In a patient with an ABI 1 and soft signs, the risk of arterial
injuries is 20%. The incidence rises to 40% in patients with an ABI of 1 and hard clinical signs
of vascular injury.
FIGURE 35-5. Coil embolization of active extravasation following blunt trauma to the
kidney. A: CT scan of the abdomen with intravenous contrast demonstrates traumatic right
renal injury with active extravasation and pooling of contrast. B: Arteriography
demonstrates brisk bleeding from branches of the lower branch of the right renal artery. C:
Renal arteriogram after coil embolization demonstrates cessation of the bleeding.
FIGURE 35-6. Coil embolization of active extravasation following blunt trauma to the pelvis.
A: Internal iliac artery angiography demonstrates bleeding (arrow) from branches of the
anterior division of the internal iliac artery. Vessel spasm is typically noted. B: Anterior
division arteriogram of the internal iliac artery after coil embolization (arrow) demonstrates
cessation of the bleeding.
CT angiography for upper and lower extremities, particularly with multidetector row CT, is
becoming the first line of diagnosis for evaluating peripheral arterial injuries. These studies can
be performed with the same contrast injection bolus used to evaluate other injuries in the chest
abdomen or pelvis.
Angiography can be both diagnostic and therapeutic for upper and lower extremity arterial
injuries. Soft clinical signs are less likely to produce angiographic evidence of injury, whereas
arterial injury requiring intervention can be found in up to 50% of cases where there are hard
clinical signs of vascular injury. The range of arterial injuries includes spasm, intimal tear,
pseudoaneurysm, extravasation, occlusion, and arteriovenous fistulas (Fig. 35-1).
The primary interventional management of arterial pseudoaneurysms is embolization but the
vessel to be embolized must be expendable. There is an 85% to 100% success rate of
transcatheter embolization, with modern catheters and coaxial techniques, for injuries in which
the vessels can be safely occluded. Transcatheter embolization is preferable to surgical ligation
where access to vascular control can be difficult, for example, profunda femoral artery.
Recently covered stents have been favored for treating injuries such as extravasation and
arteriovenous fistulas from main arteries (Fig. 35-1).
CONCLUSION
Recent years have seen a dramatic change in the manner in which patients with traumatic
vascular injury are treated. The minimally invasive nature of catheter-directed interventions
makes them an ideal alternative for many of these patients who may not tolerate open surgery
or are otherwise not candidates. Blunt trauma causing bleeding into solid organs is managed by
modern embolization techniques using temporary and/or permanent occlusion devices. Trauma
resulting in pseudoaneurysms or arteriovenous fistulas may be managed with covered stents
that serve to preserve the integrity of vessel and distal flow. These new methods have had a
major impact on the outcomes for this vulnerable group of patients.
References
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> Table of Contents > Section IV - Miscellaneous > Chapter 36 - Peripheral Vascular Sonography
Chapter 36
Peripheral Vascular Sonography
Meena Narayanswamy
Ajay Singh
Angiography has always been the gold standard for evaluation of diseases of the vasculature.
However, its invasive nature sparked the development of noninvasive modalities that were easy
to perform, were less time-consuming, and had very little, if any, morbidity. The evolution of
noninvasive methods and technology for vascular diagnosis has spanned a few decades, from
segmental pressures and plethysmography, through Doppler ultrasound, to the applications in
vogue, computed tomography (CT) and magnetic resonance (MR) angiography. Because of its
ease of use in any setting, including the outpatient clinic, and its comparable efficacy with the
newer modalities, Doppler sonography is the currently recommended first port of call in a
diagnostic workup of vascular disease. This chapter presents a brief overview of the
development of this technology and its diagnostic application in three distinct clinical settings:
peripheral arterial disease of the extremities, carotid artery disease, and deep vein thrombosis.
Obstruction and impedance to flow are the primary consequences of all vascular disease. The
obstruction can be intrinsic to the vessels when caused by conditions that directly affect the
vasculature, or it can be extrinsic, as with compression by adjacent space-occupying lesions,
trauma, or entrapment. By far the most common intrinsic disease to affect the peripheral
arteries is atherosclerosisa multicausal, degenerative disease of aging wherein the deposition
of fatty plaques inside the walls of large and medium-sized arteries causes hardening of arterial
walls, irregularity of the arterial lumen, and, ultimately, obstruction to blood flow. The incidence
of atherosclerotic peripheral arterial disease rises sharply with age and has been documented
in 2.5% of the population between 40 and 59 years, 8.3% between 60 and 60 years, and
18.8% at 70 to 79 years of age (1). Apart from aging, contributory factors such as smoking,
hypertension, diabetes, and dyslipidemia play a role in its development. The regions that
receive the most attention in the study of peripheral arterial disease are stenoses and
occlusions of the lower limb arteries and the carotid arteries in the neck.
In general, peripheral venous disease is more prevalent than arterial (2). In the United States
alone, almost 7 million individuals have clinical symptoms from varicose veins and close to 70%
of all leg ulcers are venous (3). However, they receive less emphasis both in academia and in
practice, because of their indolent nature and chronicity, as against the acute and limb-
threatening nature of arterial disease. Diseases of the peripheral veins are commonly clubbed
together under the umbrella term chronic venous insufficiency, with one exceptiondeep vein
thrombosis. Chronic venous insufficiency includes both valve incompetence or reflux (90%) and
venous obstruction (10%).
BASIC CIRCULATORY HEMODYNAMICS

From their origin in the aorta, large elastic arteries (highcapacitance vessels) demonstrate an
arboreal branching pattern into a series of smaller branches, from medium-sized arteries to
arterioles, metarterioles, up to the site of perfusion, capillaries, and the microcirculation. Veins,
also called compliance vessels, start as venules from the venous end of the capillaries and go
through a series of larger branches before emptying into the vena cavae. A capillary thus has
an arterial and a venous end and a pressure gradient must be maintained across these two
ends in order for adequate perfusion and flow to be maintained.
Flow rate, Q, is the volume of blood that passes a given area over a given time. Pressure is
force against a unit area applied to move the blood forward. Shear stress is the resistance
(force/area) applied by the wall against the moving blood. The relation among flow, pressure,
and resistance is analogous to Ohm's law of electricity, P = QR (P = pressure gradient, Q =
flow rate, R = resistance). Blood flow is thus inversely proportional to resistance: the higher the
resistance, the lower the flow rates, while the greater the pressure gradient, the higher the flow
rate. Resistance, in turn, is proportional to blood viscosity.
Flow rate is directly proportional to the cross-sectional area of the vessel multiplied by the
average antegrade flow velocity (Q = VA, where Q = flow rate, V = average velocity of flow
across the lumen, A = cross-sectional area), and therefore, the greater the diameter of the
vessel, the higher the flow rate for a given average velocity. A more important deduction of this
equation is that, for flow rate to be constant in a vessel of smaller diameter, the flow velocity
has to increase. Thus in focal areas of stenosis in arteries, the flow velocity rises in an attempt
to maintain the flow rate. This principle is exploited for diagnosing vascular stenoses when there
is a rise in Doppler velocities.
Poiseuille's law, which describes the mechanics of flow in a long cylindrical tube, is applied to
flow in arteries, even though the ideal in vitro Newtonian conditions do not prevail in the human
vasculature. Q = Pr4/8L, Poiseulle's equation (where Q = flow rate, P = pressure gradient, r
= lumen radius, L = segment length, = viscosity coefficient), not only reaffirms the relationship
among area (radius), pressure, and flow, but also defines the inverse relationship of flow
volume to viscosity and length of the vessel. Since resistance is equal to flow divided by
pressure, the same equation can be rewritten for resistance as R = 8L/r4. Resistance
increases with viscosity and with length of the vessel (4). However, it is indirectly proportional
to the vessel radius (to the fourth power). This is again a critical principle in vascular
hemodynamics and in understanding Doppler waveforms. If a vessel increases in size from 1 to
2 cm, the flow will increase by a factor of 16 and the resistance will drop by a factor of 16.
Contrariwise, if a vessel's diameter decreases from 2 to 1 cm, the resistance increases by a
factor of 16 while the flow decreases correspondingly. Overall, a region of stenosis in an artery
will therefore demonstrate (a) reduced flow, (b) increased velocity, and (c) increased
resistance.
Arterial resistance is at its maximum in the small arteries and arterioles, which are less elastic
and have more smooth muscle in their walls. They are therefore called resistance vessels.
Also, since the branching pattern of arteries is in series, the total resistance at the terminal
arteriole level is equal to the sum of all the resistances in series and is quite high. Large
arteries such as the aorta and its primary branches (carotids, vertebrals, mesenterics, etc.) are
called elastic or compliance vessels due to the large amount of elastic fibers in their walls,
which affords them a high degree of compliance. Compliance is the ability to expand and
absorb the large volumes and pressure during cardiac systole, as a result of which continuous
flow is maintained through the microcirculation. The systolic stretch in these arteries causes
them to recoil to their original diameter during diastole and this elastic recoil causes a further
wave of forward flow in late diastole. Venous vessels are thin walled and have the maximum
amount of elastic tissue in the wall. Since it takes a very large volume of fluid to increase the
pressure in veins, they are called capacitance vessels in acknowledgment of their capacity to
expand and store large quantities of blood.
The flow of blood in normal arteries is streamlined and smooth. It is called laminar flow
because the blood flows in layers (laminae) of different velocities. The layer in the center is the
fastest, the middle layers are slower, and the layer adjacent to the wall slower yet due to wall
friction caused by the viscosity of blood. Laminar flow produces a parabolic velocity profile.
Turbulent flow may occur at points where the vessel wall diverges such as at branches and
segments distal to a stenosis. Here the flow pattern loses its streamlined regularity, becomes
complex, with eddies and whorls, and the antegrade flow velocity of each layer increases,
thereby flattening the velocity profile across the lumen.
EVOLUTION AND BASIC PHYSICAL PRINCIPLES OF DOPPLER

The Doppler effect refers to the change in frequency and amplitude of a sound wave when
there is motion of either the source or the observer. Imagine a car driving toward a static
source of sound such as a church bell. The rising crescendo of the sound as the car
approaches the church, followed by the fading decrescendo as the car crosses the church and
drives away from it, is the Doppler effect. The same effect is described when the source is
moving, as happens with a truck blaring its horn on a highway. To a stationary observer, the
sound increases as the truck approaches and decreases as it passes and moves on.
In ultrasound, the piezoelectric crystal in the transducer is the source of the sound wave, which
enters the body at a predetermined frequency. As a blood vessel is imaged, the sound wave is
reflected back by the moving red blood cells, and at the same time the motion of the blood
(flow) brings about a change in its frequency, which is detected and transduced by the probe.
Frequency increases as blood flows toward the probe and decreases as it flows away. The
Doppler equation describes the relationship between the change in frequency of ultrasound
waves and the flow velocity of blood. Once the frequency shift is known, the same equation can
be reworked for flow velocity. Turbulence and the focal increase in the flow velocity that occurs
in stenotic arterial segments are used to diagnose obstructive arterial disease. The Doppler
equation, Df = 2v Cosq/c (Df = Doppler frequency shift [difference of the incident frequency
and the reflected frequency], v = velocity of blood, q = incident angle [the angle the transducer
makes with the skin], and c = speed of sound in the medium), can be reworked for flow velocity
as v = Dfc/2Cosq (4). Since the cosine of 90 degrees is zero, the transducer should not be held
at an angle perpendicular to the vessel, because from this imaging angle, no signal will be
picked up. The best Doppler signals are obtained when the incident beam forms an angle of
between 30 and 60 degrees with the skin.
Doppler ultrasound was first used in 1954 and its earliest application was in the mid-1960s, in
obstetrics, to detect the fetal heartbeat. From there, the use of this technology has spread to
encompass noninvasive diagnosis of vascular disease, where it currently is the first line of
investigation in most peripheral arterial and venous examinations (5). Modern-day vascular
ultrasound includes three fundamental technologies: gray-scale imaging of the vasculature,
pulsed Doppler spectral analysis, and color Doppler. The combination of technologies is called
duplex Doppler, though some refer to the addition of color studies as triplex Doppler or to color
Doppler as simply CFI (color flow imaging). The frequency of the probe used depends on the
region of interest. Typically low-frequency, 3.5- to 5-MHz, probes are used for deeper femoral
vessels, while higher-frequency, 7- to 10-MHz, probes are used in the superficial carotid and
neck studies (6). Early scanners used a wide continuous beam that resulted in multiple signals
from all vessels in the scan area, leading to confusion with signal and vessel identification. This
problem was surmounted in the late 1970s by transmitting a narrow beam of ultrasound, or
pulsed Doppler, in short bursts or pulses to the vessel directly under the probe face. The
received signal is transduced into a spectral waveform tracing the flow velocity throughout the
cardiac cycle (7). Flow patterns vary in arteries depending on the end organ that they perfuse.
Low-resistance flow is typically seen in arteries supplying critical organs like the brain, lungs,
heart, and abdominal viscera, while high-resistance arteries typically supply skin and muscle of
the extremities. The Doppler waveform tracing mimics the resistance patterns and helps identify
specific arteries (8). Pulsed Doppler was further refined with the development of an electronic
marker that is placed in the middle of the vessel to define the exact sample volume and for
accurate positioning of the sensitive area of the beam. The late 1980s saw the addition of
color-coding to the gray-scale images of the vessels. All the flow velocity information from the
imaged artery is collected and assigned a color code; usually it is red for flow toward the
transducer and blue for flow away from the transducer, though other hues are also used (9).
The advantages of color Doppler are ease of identification of the vessel, its patency, wall
regularity, and flow disturbance. The velocity in smooth, streamlined laminar flow in a vessel is
depicted as a tube of uniform color (red or blue; Figs. 36-1 and 36-2), while turbulence, with its
eddies and elevated velocity, presents a mlange of color pixels with intermixed reds, blues,
and all intervening hues. The wealth of information available with pulsed Doppler spectral
waveforms is not available with color Doppler alone and comprehensive imaging requires the
use of both these modalities. New innovations in Doppler technology include power Doppler and
color velocity imaging (CVI). CVI utilizes time shift rather than Doppler frequency shift data to
measure velocity directly. Power Doppler, on the other hand, uses the mean energy of the red
cells for its signal rather than the mean velocity. The color hue is dependent on the strength of
the Doppler signal, which in turn is dependent on the number of red cells in the sample volume
(10). These advances are being studied in a variety of clinical applications and are not in the
mainstream of Doppler studies at this time.
FIGURE 36-1. A patient with a significant right internal carotid artery stenosis. A: An
essentially normal Doppler waveform is noted in the left common carotid artery (CCA), with
peak systolic velocities within normal range and no flow disturbances on the color Doppler
image. B: Although the color images show slight flow disturbance distally, more importantly
the velocities and Doppler waveform are within normal limits in the proximal left internal
carotid artery (LICA), which is widely patent. C: Interrogation slightly distal to a right
internal carotid artery stenosis (RICA), with a residual lumen diameter of 2 mm, shows
markedly elevated peak systolic and diastolic velocities and filling of the spectral window
due to turbulent flow in this region. (See the color insert.)
FIGURE 36-2. Patent stent with good wall apposition. A: Longitudinal view shows a linear
echogenic signal (curved arrow) created by the metallic stent. B: Color Doppler images
confirm wide patency and excellent flow through the stent. (See the color insert.) C: An
axial image through the stent (curved arrow) confirms good apposition along the
circumference.(see color image)
Flow Patterns or Doppler Spectral Waveforms

Arteries
As mentioned above, arteries demonstrate two types of flow patterns depending on the end
organ: the low-resistance type and the high-resistance type (Fig. 36-1 and Fig. 36A-1) (8). The
low-resistance form is seen in central vessels that supply organs requiring continuous perfusion,
and therefore these arteries demonstrate a continuous forward antegrade flow. The systolic
velocity is lower, the diastolic velocity higher, and the spectral window demonstrates filling-in as
a result of plug flow (all layers of blood moving at the same velocity). The high-resistance
pattern is seen in peripheral arteries of the limbs and is described as triphasic due to a sharp
and narrow systolic spike followed by a small negative trace due to flow reversal in early
diastole and another small forward component in mid diastole due to the forward thrust of
elastic recoil (11). The systolic spike mimics the parabolic form of laminar flow with the highest
velocity in the center. The area under the trace is called a spectral window, and in normal
arteries this area is clear and devoid of signal.
FIGURE 36-3. A: Patent femoral veins are easily compressed (right panel) by pressing
externally with the transducer (curved arrow shows the noncompressed superficial femoral
vein in the left panel). B: The normal Doppler venous signal varies with respiratory (shown)
and, at times, cardiac cycles. C: Patent veins show reversal of flow during a Valsalva
maneuver. D: Augmentation of flow with external manual calf compression. (See the color
insert.)
Veins
Pulsed Doppler of veins (extremely low-resistance capacitance vessels) (Fig. 36-3)
demonstrates constant antegrade flow of very low velocity (10 to 20 cm/second in leg veins).
The waveform oscillates in tandem with respiration and the normal sinus rhythm. In hard-to-
image vessels and where patency of a vein is in doubt, enhancement of flow and Doppler signal
can be achieved by simple maneuvers like Valsalva and squeezing of the peripheral veins in the
calf.
Ultrasound Contrast Agents

Contrast agents were developed in ultrasound imaging with the intention of increasing the
reflectivity of blood, thereby improving the signal strength on both color and pulsed Doppler
scanning. The commonly used agent is microbubbles of gas, which, when injected into the
bloodstream, causes an increase in reflectivity. The main technical drawback of these agents is
that for these gas bubbles to be efficient, they should be between 5 and 10 m, at which size
the surface tension of the bubbles causes them to collapse, rendering them useless. Also, the
ultrasound pulses are themselves strong enough to disrupt and burst the gas (12,13). To
counter these problems, echo enhancing agents coated with a surfactant to lower the surface
tension have been designed. Another version uses a membrane
made of human serum albumin or a biodegradable polymer, to encapsulate the gas. Echo
enhancing contrast agents have found an application in echocardiography for the detection of
small valve leaks and, also, in transcranial Doppler of the arteries of the circle of Willis, where
they help to combat acoustic interference from the skull bones. A more recent application is in
the study of vesicoureteric reflux in children (14).
Goals of Doppler Sonography

Regardless of whether vascular disease in the peripheries is arterial or venous in nature, both
systems can be evaluated, studied, and diagnosed by Doppler sonography. The goal of
noninvasive ultrasound diagnosis is (a) to identify the disease process; (b) to define the level,
type, number, and extent of lesions; (c) to provide both the extent of anatomical disease and
the physiological functional status; and (d) to determine treatment strategies where possible.
ARTERIAL STENOSIS AND OCCLUSION

Arterial narrowing, due to whatever cause, is symptomatic only after it reaches a critical level
where it alters the regional circulatory hemodynamics and becomes clinically significant. It is
accepted practice to consider this evident when the lumen narrows to 50% of its diameter. This
degree of luminal narrowing equates to a 75% reduction in cross-sectional area. A significant
stenosis of 50% causes an increase in flow velocity and widening and filling-in of the clear
spectral window (also called spectral broadening) due to turbulence (Fig. 36-1 and Fig. 36A-2).
PERIPHERAL ARTERIAL STENOSIS/OCCLUSION OF THE

LOWER LIMB
The most common cause of peripheral arterial disease in the lower limb arteries is
atherosclerosis. The most common site of disease is the distal superficial femoral and proximal
popliteal artery segments. Diabetics have a preferential involvement of the distal limb (leg)
arteriesthe tibial and the peroneal branches.
Indications for Doppler Sonography of the Limb Arteries

1. To evaluate claudication pain and other symptoms suggestive of a vascular origin
2. To differentiate a stenosis from occlusion in symptomatic patients
3. To grade a stenosis
4. To determine the extent of an occlusion
5. To evaluate the extent of iatrogenic arterial injuries
6. To confirm the short-term technical adequacy of percutaneous transluminal balloon
angioplasty (PTA)
7. For long-term follow-up of lesions following endovascular intervention
8. To evaluate peripheral aneurysms
Technique
Scanning is performed in the supine position with the limb abducted and externally rotated and
with minimal knee flexion. A 5-MHz linear array transducer is used to systematically evaluate
the leg from the common femoral to the low popliteal artery. The transducer is placed
longitudinally over the upper thigh parallel to the proximal superficial femoral artery and the
color Doppler window is angled 20 degrees caudad. When the flow signals have been analyzed
from this segment, the transducer is shifted down a distance equal to its length and the next
segment is then studied. Systematic progress is made in this style, reviewing the entire length
of the artery until the vessel lumen is not accessible any further in the distal thigh due to the
increased depth of the adductor canal. The transducer is then placed behind the knee and the
proximal popliteal artery is examined until the anterior tibial origin is identified followed by the
tibioperoneal branches. About 10 to 12 sliding motions are required to survey the entire length
of the limb arteries. The larger the transducer footprint, the fewer the number of motions.
Using color Doppler, areas of high flow velocity (abnormal color signal) are sampled for
spectral analysis and the peak systolic velocity (PSV) ratio is calculated at these sites. At least
one velocity spectrum is required for each of the common femoral, superficial femoral, and
popliteal arteries. Any irregularity of the arterial wall is documented, as are the type, location,
and number of stenoses and/or occlusions. With aneurysms, pseudo-aneurysm, and
arteriovenous fistulas, the size is measured using electronic calipers, and details such as the
presence of thrombus, the proximal and distal limits of the aneurysm, the channel connecting
the artery and vein in a fistula, and the flow patterns within the sacs are all documented.
Color Doppler Diagnosis of Stenosis/Occlusion

1. The most significant finding in a region of stenosis is an increase in the PSV at, and
immediately distal to, the site of narrowing. Distally, the flow characteristics might return to
normal or be dampened, depending on the degree of the stenosis, the presence of occlusion,
and the extent of the collateral circulation.
2. A better indicator of stenosis is the PSV ratio, which is the PSV at the site of the stenosis to
the PSV at a normal site 2 to 4 cm proximal to the stenosis. An increase in PSV ratio of >2.2
is considered evidence of lesions causing >60% luminal narrowing that are amenable to
angioplasty if the lesion is shorter than 7 cm (15).
3. A change in the waveform from triphasic to monophasic is noted in extreme cases of
obstruction (16). However, even with less severe but hemodynamically significant obstruction,
the normal flow reversal is abolished and spectral broadening is evidenced. For occlusions
the velocity measurements proximal to the site are decreased due to increased resistance
and no spectral waveform is documented.
4. The normal PSV is 90 to 140 cm/second for the common femoral artery, 70 to 110
cm/second for the superficial femoral artery, and 50 to 80 cm/second for the popliteal artery.
Ancillary Tests
For a comprehensive evaluation of arterial disease in the limbs, two ancillary aids to diagnosis
are routinely performed. Though they do not provide any direct anatomical clues about the
extent and nature of the disease process, they can predict the presence of disease and its
approximate anatomic level: the ankle brachial index and segmental pressures (17). For the
ankle brachial index, pressures are measured at the ankle and at
the lower arm, and the ankle measurement is divided by the brachial. Values 1 are normal.
Segmental pressures take the same principle further by measuring pressure at four leg regions:
upper thigh, above knee, below knee, and above ankle. A pressure gradient of 30 mm Hg
between any two adjoining areas indicates disease in that segment of the artery.
PERIPHERAL ARTERIAL DISEASE OF THE INTERNAL

CAROTID ARTERY
Once again, the most common cause of arterial disease in this site is atherosclerosis. The
prevalence of significant internal carotid artery (ICA) disease is between 3% and 7% in the
general population; it increases with age, and exposure to risk factors such as smoking,
hypertension, and hyperlipidemia. Women tend to be less predisposed to this disease than
men. Extreme emphasis is laid on the diagnosis and treatment of ICA stenosis due to the high
risk of stroke that is attached to it. ICA stenosis can be clinically symptomatic (60% to 80% of
strokes arise from here) or asymptomatic. In symptomatic patients, the yearly incidence of
stroke increases at the rate of 5%, and it rises with increasing degree of stenosis. The 5-year
stroke risk even for asymptomatic patients increases with increasing degrees of stenosis and
ranges from 12% with a 50% to 59% stenosis to 18% with a 75% to 95% stenosis. With such
glaring statistics and in a region where the consequences are devastating, the emphasis on
diagnosis and documentation of the atherosclerotic disease cannot be overstressed.
Indications for Color Doppler Internal Carotid Artery Study

1. Evaluation of stroke, transient ischemic attack, or suspected stroke
2. Routine preoperative evaluation before major surgery, especially coronary bypass
3. Carotid bruit
4. Amaurosis fugax
5. Syncope or drop attacks
6. Neck masses or trauma to the neck
7. Follow-up of patients who have an asymptomatic untreated stenosis
8. Follow-up of patients who have undergone an endovascular revascularization procedure
Technique
The internal and the external carotid arteries are identified separately using color Doppler flow
scanning. Other clues for differentiation are as follows: (a) the ICA has the carotid bulb; (b) the
ICA is located lateral and posterior, while the external carotid artery (ECA) is medial and
anterior; (c) the ICA has no neck branches, while the ECA does; (d) the ICA has a low-
resistance flow, while the ECA demonstrates a high-resistance flow; and (e) the Doppler
waveform in the ICA does not show oscillations with the temporal tap test, while the EC
waveform demonstrates oscillations in its waveform (18). Both extracranial arteries are
surveyed completely from the jaw up to the clavicle in both longitudinal and transverse
directions. Imaging is conducted with the patient supine and the head turned 45 degrees away
from the midline toward the opposite side. Scanning is commenced from the clavicle upward
direction, in a slow transverse axis. The transverse scan helps to determine changes in the
course and location of the carotids and it also demonstrates the location of plaque deposition.
Angling the transducer caudally easily scans the origins of the ICA and ECA on the right.
Identifying the origin of the left-sided arteries is a little harder and they must be evaluated from
as proximal a position as possible. While this method is useful for demonstrating high-grade
plaques and stenosis, for assessment of the grade or severity it requires corroboration with the
longitudinal method and with the Doppler spectral waveforms. Longitudinal studies are used to
correctly position the sample volume inside the lumen for velocity and spectral analysis. Rather
than place sample volume markers in discrete positions for spectral analysis, it is
recommended that that the marker be systematically advanced throughout the vessel length so
as to not miss even a small region of focal stenosis. Scans can employ an anterolateral
approach using the sternocleidomastoid as the marker or a more posterolateral approach using
the jugular vein as an acoustic window.
Imaging gaps produced by calcified plaques can mask underlying high-grade stenoses. One
way of approaching such areas is to scan from a posterolateral angle while simultaneously
having the patient turn his or her head to the same side. This technique sometimes opens a
new acoustic window for imaging. Representative velocity measurements should be obtained
from the proximal, mid, and distal segments of both the common carotid artery (CCA) and the
ICA. The distal segment sample of the ICA should be at least 3 cm beyond the bifurcation.
Color Doppler Diagnosis of Stenosis/Occlusion

1. In contrast to the peripheral arteries, the carotids have forward antegrade flow throughout
the entire duration of the cardiac cycle since they supply a critical end organ that requires
constant perfusion. The negative flow reversal is therefore not a feature here. ICA flow is
monophasic, low-resistance flow type, with good systolic and diastolic flow (Fig. 36-1). The
diastolic velocity is higher than that in the ECA. The PSVs in the ICA range from 80 to 100
cm/second for the average adult and between 60 and 80 cm/second for older people. The
ECA shows a high-resistance type of flow with a sharp systolic spike and a small diastolic
component due to its numerous branches to the face and the neck. The CCA flow pattern is a
combination of the two, demonstrating both the systolic spike and the higher diastolic flow
velocities.
2. Hemodynamically significant stenosis demonstrates an increased PSV at and immediately
distal to the site of the stenosis compared with the ipsilateral CCA (19). A PSV of 125
cm/second is considered to be a good indicator of significant narrowing of the ICA (Fig. 36-
1). End diastolic velocity >100 cm/second is a strong indicator of a stenosis of high degree
(>70%) in the ICA. End diastolic peak flow velocities have recently been studied as a
possible prognostic indicator of stroke.
3. With a high-grade ICA stenosis, flow velocities in the more proximal CCA drop. This serves
as a supportive clue to the stenosis higher up. Furthermore, when there is proximal occlusive
disease, the distal poststenotic segment velocities, because of which it is dubbed the parvus
tardus, have a flow pattern that shows a slow systolic climb and low pattern (20).
4. PSV ratios are another method of assessing stenosis. A ratio of the proximal measurement
to the stenotic measurement >2 suggests a >50% stenosis; a ratio >4 suggests a >75%
stenosis.
5. It is at times difficult to differentiate between a normal artery and a suboccluded artery with a
very high-grade stenosis, since the very poor flow in the latter causes a drop in velocities,
which can be misleading. Color Doppler scanning, measurement of the arterial lumen (normal
diameters are 5 to 6 mm in males and slightly smaller in women), and compensatory
sympathetic increase in flow in the contralateral CCA are helpful indicators of a lesion. High
intracranial stenoses or dissections can demonstrate proximal low diastolic flow velocities
and a Doppler tracing that now simulates a high-resistance pattern akin to that of the ECA.
The ECA tap test will help determine if the interrogated vessel is in fact the ECA or an ICA
with a lesion above the neck.
6. Spectral broadening or color mosaic pattern indicative of turbulence just distal to the site of
significant stenosis is yet another supportive feature.
DOPPLER SCANNING IN DEEP VEIN THROMBOSIS

DVT most commonly affects the lower extremities, though it can occur in other venous beds
too. It is an important cause of morbidity and mortality for two reasons. (a) It often has an
insidious presentation, which is difficult to diagnose clinically. Therefore the assessment of
incidence or prevalence of this disease is often an estimated figure, since in the average clinical
setting, most episodes miss detection and are only picked up retrospectively, after they cause
disastrous consequences. (b) The major source of pulmonary embolism, a potentially fatal
condition, is DVT in the lower limbs. Recent studies have shown that the incidence of pulmonary
emboli in asymptomatic patients, who died in hospital of unknown causes, is close to 30%. In
those with symptomatic DVT, the incidence of pulmonary embolism approximates 10% to 15%.
Although DVT can develop in the below-knee calf veins and in the above-knee femoropopliteal
veins, the latter is the bigger contributor to pulmonary embolism. Venous ultrasonography has
come to be the gold standard in the diagnosis of lower limb DVT and has totally replaced
invasive venography in this arena, owing to its high diagnostic accuracy.
Indications for Venous Ultrasound of the Leg (21)

1. Acute onset of lower extremity swelling or pain raising suspicion of acute DVT
2. To establish a baseline study following the completion of anticoagulation treatment for DVT
for a comparative assessment with future venous studies
3. Evaluation of high-risk but asymptomatic patients for DVT (postsurgery, especially for hip
replacement, the bedridden, posttrauma, etc.)
4. Preoperative assessment of the saphenous vein prior to coronary artery bypass
5. Detection and segmental analysis of venous reflux in patients with obesity, varicose veins, or
venous stasis with or without cutaneous ulceration
Technique
Scanning is conducted with the patient in the supine position or if the veins are hard to image,
the limb is placed in a slightly dependent position or in the reverse Trendelenberg position to
engorge the veins. The examination starts at the groin by identifying the common femoral vein
seen in close approximation to the artery. Distinguishing the vein from the artery is aided by the
vein's compressibility upon transducer pressure, location, and branching pattern, Doppler
waveform, and color Doppler (Fig. 36-3). The confluence of the greater saphenous vein into the
common femoral vein must always be identified. Three to five centimeters below this the
common femoral vein bifurcates into the deep femoral and the superficial femoral veins. The
deep femoral vein lies superior and medial to the artery, while the superficial femoral lies deep
to the corresponding artery. These veins are traced in the same manner as in scanning for the
limb arteries, down the thigh to the adductor canal. Since the vein lies deep in the canal,
imaging might be difficult and might require additional techniques to provide a better acoustic
window. The prone position, with the knee flexed and lightly fixed, and the supine position, but
with the leg abducted and the knee flexed, are two such positions in which the vein can be
imaged with the transducer placed behind the knee and moved upward with a cranial
angulation. Inferior movement of the transducer down the knee and over the lateral posterior
calf is continued in the same position with the leg abducted and the knee slightly flexed. The
popliteal and the tibioperoneal veins are easily imaged in this position. Scanning from the medial
side of the calf is useful for identifying the posterior tibial and the peroneal veins.
Additional techniques such as scanning the dependent limb with the patient sitting on the edge
of the bed, or sitting erect, distend the vein and make it more identifiable. Flow augmentation
methods such as squeezing the calf veins and the Valsalva maneuver reconfirm vessel patency
by causing a temporary engorgement of the proximal veins that can be visualized (Fig. 36-3).
Doppler Diagnosis of Deep Venous Thrombosis

Since the veins are extremely distensible capacitance vessels with low resistance, the flow
pattern of a normal vein also is of the low-resistance type, with constant antegrade flow and
low systolic and diastolic velocities. Oscillation of the waveform with both respiration and sinus
rhythm is normally present (Fig. 36-3).
Three diagnostic criteria determine the diagnosis of acute DVT (22):
1. Visualization of thrombus within the vessel: Detection of thrombus is dependent on the age of
the thrombus and the acoustic density. A fresh thrombus has a density close to that of blood
and therefore the scanner might not be able to resolve it as separate from blood. Echogenic
thrombus is visualized as either partially or completely obstructing the lumen. Recanalization
of thrombus will show a persistent echogenicity in the walls of the vein. On color Doppler an
indentation of the color signal of the lumen indicates the presence of thrombus. Irregularity of
the color column alongside numerous collateral channels is suggestive of a chronic thrombus.
2. Passive distension of the vein and absence of the normal venous compressibility (Fig. 36-4)
(23): In the face of thrombus identification being dependent on its echogenicity, loss of
compressibility is the most important criterion for diagnosis of DVT. To demonstrate this, the
vein must always be imaged in the transverse direction. The transducer is used to press
down the skin and the soft tissues over the vein and the pressure is held or increased until
apposition of the walls of the vein is seen.
The transducer is walked down the length of the vein and the procedure repeated. Also, the
presence of thrombus inside the venous lumen causes the vein to expand and this distension
may cause the pain in DVT.
3. Change in flow dynamics: If the vein is totally occluded, there can be total absence of flow.
With partial obstruction, loss of the phasic oscillation with respiration is noticed (24). Also,
flow augmentation methods are not successful (25).
FIGURE 36-4. Acute thrombus in deep femoral veins makes them look engorged (arrows);
the veins lose normal respiratory variation, fail to respond to Valsalva and augmentation
maneuvers, and cannot be compressed by external transducer pressure (right panel). An
indirect sign of venous obstruction is the presence of small collateral veins in the soft
tissues around the obstructed segment. With chronic total occlusions, the vein diameter is
narrowed; collaterals and functional abnormalities are commonly seen.
CONCLUSION
Vascular sonography is the mainstay of initial noninvasive imaging of arterial and venous
disease in a variety of clinical settings. In the neck and extremities, it is employed widely for the
pre- and postoperative evaluation of carotid artery stenoses, lower extremity atherosclerosis (in
conjunction with segmental Doppler evaluation), and acute and chronic venous obstructive
disease. Although the technique is operator dependent, good quality-control requirements
assure high sensitivities and specificities for diagnosis comparable to or better than those of
other existing, often more invasive, methods.
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Appendix
FIGURE 36-A1. Blood Flow Waveforms in the Extremities (velocity versus time) A: The
normal triphasic pattern in peripheral arteries shows a prominent antegrade peak during
systole, followed by a short period of flow reversal during end-systole. The quality of
antegrade pattern in late diastole reflects a response to normal and abnormal physiological
changes. B: When there is an inflow obstructive lesion, the velocities are low but the
pattern is monophasic, reflecting a (normal compensatory) low distal resistance. C: In the
presence of a distal obstruction, the velocities are low and the pattern is biphasic,
reflecting high distal resistance. D: An arteriovenous fistula with direct shunting of blood
from the arterial to the venous systems is manifested by high peak velocities and a
monophasic pattern of low distal resistance. E: A biphasic-reciprocating pattern of sharp
antegrade flow with reversed flow sustained through diastole is seen in a
pseudoaneurysm. The color Doppler image shows a typical yin-yang sign (see Figure 5-
11 on pages 65 and 66).
FIGURE 36-A2. Doppler Spectral Waveforms adjacent to an Arterial Stenosis. In the
presence of an arterial stenosis: A: the flow is laminar proximally and velocities may be
reduced; B: at the neck of the narrowing, peak flow velocities are markedly increased with
minimal widening of the spectrum. Just distal to the stenosis, there is a central lumen
antegrade jet with flow reversal toward the wall reflected: C: in the spectral waveform by
markedly increased peak systolic velocities and a widening of the spectral window (and in
the typical flow patterns noted on color images), and D: the disturbed flow patterns of
reversed flow and turbulence.
> Back of Book > Color Plates
Color Plates
FIGURE 1.1. (see black and white image)















Peripheral Vascular Interventions

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Peripheral Vascular Interventions

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CONTRIBUTING AUTHORS P.vii

Joyoni Dey PhD

Anne Hamik MD, PhD

Shozo Hirota MD, PhD

Priya Jagia MD, DNB

Ashu Jhamb MBBS

Krishna Kandarpa MD, PhD

Gi-Young Ko MD, PhD

Stuart Lyon MB, BS

Peter Y. Milne MB. BS

Robert J. Min MD, MBA

Meena Narayanswamy MBBS, MD

Jae Hyung Park MD

Jean-Pierre Pelage MD, PhD

Martin R. Prince MD, PhD

Frank J. Rybicki MD, PhD

Sanjiv Sharma MBBS, MD

Harneil Singh Sidhu MD

Ajay K. Wakhloo MD, PhD

Robert I. White Jr. MD

PATHOBIOLOGY OF PERIPHERAL ARTERIAL DISEASES

LOWER EXTREMITY ATHEROSCLEROTIC PERIPHERAL

Clinical Presentation and Evaluation

TABLE 1-1 INDIVIDUALS AT RISK FOR LOWER EXTREMITY PERIPHERAL

Age 50-69 years and history of smoking or diabetes

Legs symptoms with exertion (suggestive of claudication) or ischemic rest pain

Abnormal lower extremity pulse examination

Known atherosclerotic coronary, carotid, or renal artery disease

Grade Category Clinical description Objective criteria

0 0 Asymptomatic Normal treadmill test

Ankle pressure after exercise <50

I 1 Mild claudication More moderate symptoms

Does not complete treadmill test;

Resting ankle pressure <60 mm Hg;

II 4 Ischemic rest pain

Resting ankle pressure <40 mm Hg;

Major tissue loss above the

Noninvasive Vascular Testing

TABLE 1-3 CLINICAL CATEGORIES OF ACUTE LIMB ISCHEMIA

Noninvasive laboratory testing provides physiological information such as limb perfusion

FIGURE 1-4. Segmental pressure measurements. Sequential Doppler pressures are

TABLE 1-4 DIFFERENTIAL DIAGNOSIS OF EXERTIONAL LEG PAIN

Nonatherosclerotic vascular disease

Popliteal artery entrapment

Exertional compartment syndrome

Endofibrosis of the external iliac artery

Giant cell arteritis

ABDOMINAL AORTIC ANEURYSMS

As in atherosclerosis, the development of aortic aneurysms involves inflammatory mediators

Clinical Presentation and Evaluation

Iliac, Femoral, and Popliteal Artery Aneurysms

RENAL ARTERY DISEASE

Clinical Presentation and Evaluation

Renal Artery Aneurysms

MESENTERIC ARTERY DISEASE

Clinical Presentation and Evaluation

EXTRACRANIAL CAROTID ARTERY STENOSIS

Clinical Presentation and Evaluation

2. Libby P, Ridker PM, Maseri A, Inflammation and atherosclerosis. Circulation.

8. Gu L, Okada Y, Clinton SK, et al. Absence of monocyte chemoattractant protein-1

13. Ross R. Atherosclerosisan inflammatory disease. N Engl J Med. 1999; 340(2):115-

15. Faggiotto A, Ross R, Harker L. Studies of hypercholesterolemia in the non-human