Primary Myocardial Disease

Introduction

Cardiomyopathy – myocardial disease not attributable to ischemic damage of pressure or volume overload. Heart muscle disease with no known etiology.

Specific heart muscle disease – known association or cause.

Myocarditis – reserved for inflammatory cardiac muscle disease related to viruses or other agents.

Primary Myocardial Disease: Disease of MUSCLE, commonly associated with CHF; need to exclude ischemic heart disease, HTN, valvular disease, congenital heart disease

Noninflammatory – cardiomyopathy: congestive, hypertrophic, restrictive
Inflammatory – myocarditis

Congestive (Dilated) Cardiomyopathy

Etiology: Idiopathic, alcoholic, infection, peripartum, toxic, Keshan

Gross changes: large globoid heart, hypertrophy obscured by dilation, mitral insufficiency, often contain mural thrombi, endocardial fibrosis.

Microscopic changes: myocyte hypertrophy, focal degeneration and atrophy, interstitial fibrosis.

Functional considerations: <40% Left ventricular ejection fraction, impairment of contractility (systolic dysfunction); hypocontracting heart.

Pathogenesis

Genetic – 20% have 1st degree relatives
Immune – humoral and cellular defects, antimyocardial antibodies to myosin heavy chain, T-cell activation against heavy chain
Viral infection – high viral antibdoy titers, viral specific RNA, however PCR results conflicting

Hypertrophic Cardiomyopathy

Also termed: idiopathic concentric hypertrophy, asymmetric septal hypertrophy (ASH), idiopathic hypertrophic subaortic stenosis (IHSS)

Hypertrophy of LV free wall vs. septum: symmetrical or asymmetrical hypertrophy, with or without LV outflow tract obstruction.

Gross changes: marked cardiac hypertrophy, symmetrical or asymmetrical septum, small LV cavity, subaortic endocardial scar (patch of endocardial fibrosis where the anterior mitral leaflet impinges on thickened septum), atrial dilatation.

Microscopic changes: severe myocyte hypertrophy and disarray usually oriented in one direction (distinguishes from congestion), degeneration, atrophy, and interstitial fibrosis. Myofibrillary dissarray can also be seen on EM.

Functional considerations: impaired diastolic filling (compliance) of massively hypertrophied left ventricle, 50-80% ejection fraction, hypercontracting heart

Pathogenesis

genetics – 50% autosomal dominant, at least 5 genes on 4 chromosome involved: 30 % myosin heavy chain, 15% troponin TI

Restrictive Cardiomyopathy

A primary decrease in ventricular compliance (Ý endomyocardial rigidity), resulting in impaired ventricular filling during diastole. May mimic constrictive pericarditis.

Restriction of ventricular filling with normal or small LV cavity

Need to rule out: constrictive pericarditis, diffuse cardiac amyloidosis, cardiac hemochromatosis

Endomyocardial fibrosis (tropical climates) and Loeffler’s endomyocarditis (temperate)

Fibrotic plaques and mural thrombi in ventricular inflow tracts causing "trapping" of AV valves with mitral and tricuspid insufficiency. Loeffler’s syndrome–eosinophils, visceral infiltrates, anemia, splenomegaly,CNS symptoms. Pathogenetic role of activated eosinophils and mast cells leading to cell damage and thrombosis Þ fibrosis.

Endocardial Fibroelastosis

Especially in infants under 2 years, thick opaque layer of fibroelastic tissue usually in left ventricle +/- RV.
Etiology: probably represents a nonspecific reaction to raised ventricular wall tension in a growing heart (infant endocardium). Associations: familial genetic basis, associated congenital anomalies, metabolic, intrauterine viral infections or hypoxia.
Pathology – hyperplastic aortic valve

Cardiac Amyloidosis: patchy replacement of myocardial fibers by amyloid fibers. Histologically – orange color, stain with Congo-red.

Right Ventricular Dysplasia (arrythmiogenic RV dysplasia)

replacement of all RV muscle by fibroadipose tissue; occurs typically in young males; associated with ventricular tacharrhythmia and LBBB; presents with palpitations, tachycardia, syncope, sudden death

Types:

parchment RV (Uhl’s anomaly)
focal RV muscle atrophy: replacement with fibrofatty tissue or myocyte degeneration and focal inflammation.

Regarded as a type of RV cardiomyopathy

Myocarditis

Inflammatory myocardial injury

Present with silent MI, CHF, sudden death

Diagnosis: clinical presentation, gallium scans, biopsy is the ONLY method for confirmation.

Etiology of myocarditis:

Viruses (Coxsackie A&B, Echo, Influenza)
Bacteria (Dipththeria, TB, Strep)
Fungi (aspergillus, candida, crypto)
Protozoa (toxoplasma, trypanosoma (Chagas’))
Metazoa (echinococcus, trichinella)
Immune (Rheumatic fever, SLE, scleroderma, transplant rejection)
Drugs (methyldopa, penicillin, sulfas))
Physical Injury (radiation, heat stroke)
Unknown (sarcoid, giant cell myocarditis, Kawasaki’s).

Gross changes:

Acute – flabby dilated heart
Chronic – progressive fibrosis

Microscopic changes:

Acute suppurative – bacteria, fungi
Interstitial (lymphocytic) – viral, Coxsackie
Parenchymatous (focal dropout) – parasites eg. Toxo, Chaga’s
Granulomatous – sarcoid, TB, Wegener’s, Fiedler’s

Dallas criteria – myocardial inflammatory infiltrate adjacent to myocyte necrosis and/or degeneration

Endomyocardial Biopsy Diagnosis

First biopsy: myocarditis (with or without fibrosis), borderline myocarditis (may need biopsy), no myocarditis
Subsequent biopsies: ongoing (persistent) myocarditis, healing (resolving) myocarditis, healed (resolved) myocarditis. (All can be with or without myocarditis)

Possible outcomes of acute viral myocarditis:

complete recovery, sudden death, rapid progressive chronic myocarditis, chronic myocarditis Þ Idiopathic congestive cardiomyopathy

Endomyocardial biopsy

Recently developed, non-operative, technique of endomyocardial biopsy now enables us to histologically examine the heart during life. It involves the insertion of a specialized biopsy catheter transvascularly usually into the right side of the heart, but occasionally left-sided biopsy is also performed.

Complications: 1% complication rate, 0.03% mortality rate; complications include perforation of RV free wall, cardiac tamponade, R pneumothorax, vasovagal reaction, arrhythmia, infection, embolism, nerve palsy

Specific disorders diagnosed: Acute allograft rejection, myocarditis, anthracycline toxicity, cardiac amyloidosis, cardiac sarcoidosis, glycogen storage disease, hemochromatosis, endocardial fibroelastosis, cardiac tumors.

Tumors of the Heart

Benign (70%): include myxoma (30%), lipoma, rhabdomyoma, fibroelastoma, hemangioma, teratoma, mesothelioma of AV node.

Malignant (30%): include angiosarcoma (10%), rhabdosarcoma, mesothelioma, fibrosarcoma, malignant lymphoma.

Metastatic tumors (40X more common than primary tumors), most frequent include leukemia, melanoma, lung, thyroid, sarcomas

Indications for Endomyocardial Biopsy: Diagnosis and follow-up of acute cardiac allograft rejection; diagnosis and follow-up of myocarditis, diagnosis of anthracycline toxicity, diagnosis of secondary cardiomyopathies.

Limitations: High sensitivity but very low specitivity; many false negatives!!

negative results mean nothing – related to sampling.