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 b. Hypertension c. Aortic and mitral valve disease d. Myocardial disease 2. 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. Brain - cerebral hypoxia - irritability, loss of attention

span, restlessness, stupor and coma D. Right-sided heart failure 1. Pathogenesis a. Pure - cor pulmonale, tricuspid or pulmonic valve lesions b. Consequence of left-sided failure - mitral stenosis and

left-to-right shunts c. Other - myocarditis, cardiomyopathy, constrictive

pericarditis 2. 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

d. Subcutaneous tissue - peripheral edema, anasarca e. Pleural spaces - effusions f. Brain - venous congestion and hypoxia g. Portal system - ascites II. 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. 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 C. 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.

4. Storage disease - glycogen, Fabry's disease 5. Infiltrative - sarcoidosis B. 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.