Pathology 6020 - Year 05

Frederic Clayton, MD
Dec. 2, Friday
10:00-11:00 am
CONGESTIVE HEART FAILURE, CARDIOMYOPATHY AND MYOCARDITIS
I.
Congestive heart failure
A.
Definition - the pathophysiologic state resulting from impaired cardiac
function rendering the heart unable to maintain an output sufficient for
the metabolic requirements of the tissues and organs of the body.
CHF occurs either because of a decreased myocardial capacity to
contract or because an increased pressure-stroke-volume load
imposed on the heart.
Systolic dysfunction - deterioration of myocardial contractility
Diastolic dysfunction - insufficient expansion to accommodate
ventricular volume
B.

Mechanisms of compensation
1.
Tachycardia
2.

Frank-Starling mechanism - increased end-diastolic volume

causes increased stroke volume (more venous return increases
blood flow)

3.

Myocardial hypertrophy - not hyperplasia

4.

Catecholamines by the adrenal medulla increase myocardial

contractility

5.

Renin-angiotensin-aldosterone system increases blood volume

6.

Adrenergic-mediated redistribution of blood flow

7.

Increased oxygen extract from hemoglobin

C.

Left-sided failure
1.
Usual causes
a.
Ischemic heart disease

2.

b.

Hypertension

c.

Aortic and mitral valve disease

d.

Myocardial disease

Systemic effects
a.
Lungs - pulmonary edema and congestion

Pale pink edema fluid filling alveoli

Lung alveolar hemorrhage,

heme-filled
macrophages heart failure
cells, with
iron stain to right

dyspnea - breathlessness
orthopnea - dyspnea lying down (increased venous
return)
paroxysmal nocturnal dyspnea - extreme dyspnea in
bed, bordering on suffocation
cough - frothy, blood-tinged sputum
b.

Kidneys - reduction in renal perfusion causes ischemic

tubular necrosis and prerenal azotemia

Kidney -ATN

c.
D.

Brain - cerebral hypoxia - irritability, loss of attention

span, restlessness, stupor and coma

Right-sided heart failure

1.
Pathogenesis
a.
Pure - cor pulmonale, tricuspid or pulmonic valve lesions

2.

b.

Consequence of left-sided failure - mitral stenosis and

left-to-right shunts

c.

Other - myocarditis, cardiomyopathy, constrictive

pericarditis

Systemic effects
a.
Liver - chronic passive congestion, central hemorrhagic
necrosis, cardiac sclerosis
Liver chronic
passive
congestion
blood pools
near the central
veins

Liver chronic
passive
congestion

Liver chronic
passive
congestion
blood pools
near the central
veins

Liver chronic
passive
congestion
red cell pooling
near central
veins
and pericentral
necrosis of the
hepatocytes

b.

Spleen - congestive splenomegaly

c.

Kidneys - congestion and hypoxia

II.

d.

Subcutaneous tissue - peripheral edema, anasarca

e.

Pleural spaces - effusions

f.

Brain - venous congestion and hypoxia

g.

Portal system - ascites

Myocarditis
A.
Clinical significance
Frequency of the disease is unclear symptoms are nonspecific so
diagnosis is often missed. Most cases are probably of viral origin.
Symptoms and signs depend on the etiology and severity - vary from
sudden congestive heart failure to fatigue, dyspnea, palpitations and
fever. ECG may show diffuse ST-T segment changes and chest x-ray
may show cardiac dilatation.
B.

C.

Classification by etiology
1.
Viral - Coxsackie A and B, ECHO, influenza, poliomyelitis, viral
hepatitis, EBV, and cytomegalovirus
2.

Chlamydia - C. psittaci

3.

Rickettsia - R. typhi (typhus fever) and R. tsutsugamushi (scrub

typhus)

4.

Bacteria - diphtheria, salmonella, TB, strep, meningococcus,

leptospira, Borrelia

5.

Fungal and protozoa - trypanosoma (Chagas' disease),

candida, toxoplasmosis, aspergillus, Blastomyces, cryptococci,
and coccidiomycosis

6.

Metazoa - echinococcus, trichinella

7.

Hypersensitivity - RHD, SLE, systemic sclerosis, drugs

8.

Physical agents - radiation, heat stroke

9.

Idiopathic - giant cell myocarditis

General morphology
1.
Gross - cardiac dilatation, flabby myocardium with pale patches
of yellow-gray and hemorrhage on the cut surface

Dilated, globoid
heart in
myocarditis

2.

Microscopic - interstitial inflammatory infiltrate with focal

myocyte necrosis and focal fibrosis. Type of infiltrate is
suggestive of the etiology.
Myocarditis meets
Dallas criteria of a T
lymphocyte
infiltrate and
myocyte
necrosis or
dropout. This is
usually either viral
or of unknown
cause.

mononuclear - most types including idiopathic

neutrophils - bacteria

eosinophils - hypersensitivity, protozoa, Metazoa

D.

Specific entities
1.
Viral - most common etiology of myocarditis and is difficult to
diagnose - rising viral titers and endomyocardial biopsy viral
cultures. EM has not been productive. May develop into
congestive cardiomyopathy.
2.

Bacteria - direct heart invasion with suppurative response.

Diphtheria produces an exotoxin which causes myocyte necrosis.
Diphtheria myocarditis
due to a toxin rather
than bacterial
invasion. There is
some inflammation,
myocyte changes (see
the big nucleolus).
Myocyte necrosis
(not shown) also
happens.

Bacterial colony in
myocarditis

3.

Protozoa
Toxoplasmosis (infected soil passed to pets and man) affects
young and immunocompromised host (heart transplant
patients).

Toxoplasmosis

Trypanosoma (Chagas' disease) - passed in the feces of the

Reduviidae bugs and penetrate broken skin or intact mucous
membranes. Parasitization of myocytes with inflammatory
infiltrate and the formation of pseudocysts. Fibrosis and
congestive heart failure may be seen.
Chagas
disease

4.

Hypersensitivity reactions - numerous drugs and toxins

5.

Giant cell myocarditis - myocyte necrosis with multinucleate

giant cells, lymphocytes, plasma cells, macrophages, and
neutrophils. Often fulminant with rapid progression to death.

III.

Cardiomyopathy - heart muscle disease of unknown etiology

A.

Dilated or congestive cardiomyopathy

1.
Morphology
Gross - increased weight, dilatation of ventricle, mild
endocardial thickening, normal coronary arteries and valves

Dilated Cardiomyopathy
Microscopic - myocyte hypertrophy with large, bizarre nuclei;
myofibrillar loss, and interstitial fibrosis

Cardiomyopathy
loss of myofibrils

Cardiomyopathy
trichrome stain
showing extensive
fibrosis (blue)
between
the myocytes. The
myocytes also vary
in size, and some
have partial loss of
myofibrils.

Normal Heart - EM

Loss of fibrils in
cardiomyopathy.
The myocyte at
lower left is about
normal; the
others have an
extensive loss of
myofibrils.

Cardiomyopathy
loss of fibrils
and a small
contraction band
in the top center.

2.

Etiology:
alcohol
toxins
selenium deficiency (Keshan's disease)
viral
genetic

3.

Clinical significance:
cardiac failure
atrial fibrillation with thrombosis and embolism
death

B.

Hypertrophic cardiomyopathy (IHSS, ASH)

1.

Morphology
a.
Disproportional hypertrophy of ventricular septum (95%)
b.

Myofiber disarray (100%)

c.

Reduction in the volume of ventricular cavities (90%)

d.

Endocardial thickening in the left ventricular outflow tract

(75%)

e.

Mitral valve thickening (75%)

f.

Dilated atria (100%)

g.

Abnormal intramural coronary arteries (50%)

Hypertrophic
cardiomyopathy

Hypertrophic
cardiomyopathy

Hypertrophic
cardiomyopathy

Hypertrophic
cardiomyopathy
myofiber dysarray
not all fibers are
pulling
the same direction.
Thus the contraction
is ineffective.
However, the cardiac
conduction system
can have these same
problems, which
might cause the
arrhythmias and
sudden death these
patients tend to die
of.

2.

Etiology - genetic usually autosomal dominant, occasionally

sporadic. Due to mutations of any of several contractile-related
proteins.

3.

Clinical significance
Symptoms - dizziness, syncope, LV failure, arrhythmias,
reduction of cardiac output by obstruction and reduced LV
volume, reduced LV compliance, sudden death rate 2-6% per
year.

C.

Restrictive/infiltrative/obliterative cardiomyopathy - restrict cardiac

filling
1.
Endomyocardial fibrosis children and young adults in Africa
with fibrosis of one or both ventricles. Subendocardial scarring
involving inner third of myocardium. Unknown etiology, might
be due to high food serotonin levels.
Endomyocardial
fibrosis fibrosis
under the
endocardium and
in the the inner
third of the
myocardium.

Endomyocardial
fibrosis of a
ventricular wall.
When extensive,
this would cause
restrictive heart
failure too.

2.

Loeffler's endocarditis - endomyocardial fibrosis, eosinophilic

leukocytosis, myocardial necrosis and eosinophilic infiltrate,
fibrosis, heart failure.

3.

Endocardial fibroelastosis - focal or diffuse fibroelastic

thickening of the endocardium without myocardial necrosis.
Unknown etiology - hereditary, hypoxic, pressure overload,
lymphatic obstruction, or viral.
Endocardial
fibroelastosis
elastic stain (black)
is very positive.
This disease,
which occurred in
young children and
was once 1:5,000
births, now is
almost never seen.
Etiology is not
known (? viral such
as mumps).

Endocardial
fibroelastosis

4.

Infiltrative cardiomyopathies such as amyloidosis and

hemochromatosis.
Amyloidosis
notice the pink
material between
the myocytes.

Amyloidosis
Congo Red is very,
very positive.

Amyloidosis this
heart is thickened,
pale, and has a
rubbery
consistency that
interferes with
cardiac expansion
during diastole.

IV.

Specific heart muscle disease

A.
Classification
1.
Toxic - alcohol, cobalt, catecholamines, Cocaine, Adriamycin
By electron
microscopy, this
was Adriamycin
toxicity. See the
clear vacuoles
(they
are dilated
sarcoplastic
reticulum) and
severe loss of
myofibrils.

Cocaine heart
necrosis with
contraction bands.
This could happen
with any
severe chronic
stimulation such as
too much pressors in
a failing heart or a
pheochromocytoma.

2.

Metabolic - hemochromatosis, nutritional deficiency, thyroid

disease

3.

Neuromuscular disease - Friedreichs ataxia, muscular

dystrophy
Heart - Beckers
muscular
dystrophy looks
like idiopathic
dilated
cardiomyopathy

Note the fibrosis and

loss of myofibrils in
some cells.

B.

4.

Storage disease - glycogen, Fabry's disease

5.

Infiltrative - sarcoidosis

Sarcoidosis - noncaseating granulomata replacing heart muscle and

healing with fibrosis (20-30% heart involvement).
Cardiac Sarcoidosis
well defined
granuloma with giant
cells. Dosent
infiltrate &
destroy myocardium
like giant cell
myocarditis.
Eosinophils are less
common in
sarcoidosis than in
giant cell
myocarditis.

C.

Hemochromatosis - myocardium and conduction system with heart

failure and arrhythmias either primary or secondary.

Hemochromatosis note the brown

perinuclear
deposits of
hemosiderin. It is,
however, the
soluble iron, not
the hemosiderin,
that is considered
toxic.

Hemochromatosis
iron stain (iron is
blue).

D.

Rheumatoid heart disease - rheumatoid nodules within arteries,

valves, myocardium, and pericardium.

Rheumatic fever Aschoff body A collection of cells,

often near a vessel, with a
few multinucleate cells and some vesicular nuclei with
big nucleoli (Aschoff cells). Anichkov myocytes (not
shown) are myocytes with very elongated big nucleoli.
This is a marker for rheumatic fever, but the serious
damage is to the valves.