6 myocarditis

Myocarditis

• An inflammatory process of myocardium that result into the injury to cardiac myocytes.

Major Causes of Myocarditis

INFECTIONSViruses(coxsackie,influenza,HIV,CMV)Chlamydia(C.Psittaci)Rickettsiae(R.typhi)Bacteria(Cornybacterium diphtheriae,Nisseria men

ingococcus,Borellia)Fungi(Candida)Protozoa(trypanosoma Cruzi,toxoplasmosis)Helminths(trichinosis)

IMMUNE-MEDIATED REACTIONS

• Post viral• Post Streptococcal• SLE• Drug hypersensitivity(e.g.methyldopa,sulphonamides)• Transplant rejections

UNKNOWN

Sarcoidosis

Giant cell myocarditis

Morphology

• Active phase – heart may be normal or dilated• Advanced stages: the ventricular myocardium is fl

abby and often mottled. • Mural thrombi may be present in any chamber.

• Mononuclear interstitial inflammatory infiltrate associated with focal myocyte necrosis.

• Later-inflammatory lesions either resolve, leaving no residual changes, or heal by progressive fibrosis.

Hypersensitivity myocarditis- perivascular interstitial infiltrates, composed of lymphocytes, macrophages, and a high proportion of eosinophils

Giant-cell myocarditis (uncertain cause)- • inflammatory cellular infiltrate containing multinu

cleate giant cells interspersed with lymphocytes, eosinophils, plasma cells, and macrophages.

• Chagas disease: trypanosoma cruzi, mixed inflammatory cell infiltrate.

Chagas disease - scattered trypanosomes accompanied by an inflammatory infiltrate of neutrophils, lymphocytes, macrop

hages, and occasional eosinophils

Clinical Features

• May be asymptomatic- recover completely without sequelae

• Features of heart failure or arrhythmias, occasionally with sudden death.

• fatigue, dyspnea, palpitations, precordial discomfort, and fever.

• Occasionally, patients develop DCM - late complication of myocarditis.

OTHER CAUSES OF MYOCARDIAL DISEASE

Adriamycin, doxorubicin and daunorubicin

Catecholamines

Cyclophosphamide

Amyloidosis

Amyloidosis

• caused by deposition of an insoluble extracellular fibrillar deposits of protein fragments that are prone to forming β-pleated sheets.

• Cardiac amyloidosis may appear along with systemic amyloidosis

• restricted to the heart, senile cardiac amyloidosis.

• amyloid deposits generally occur in the ventricles and atria.

• caused by the deposition of transthyretin

Morphology

• normal to firm and rubbery. • Usually the chambers are of normal size• Can be dilated and have thickened walls. • Numerous small, semi-translucent nodules resem

bling drips of wax • Eosinophilic deposits of amyloid may be found in t

he interstitium, conduction tissue, valves, endocardium, pericardium, and small intramural coronary arteries

• special stains - Congo red- classic apple-green birefringence when viewed under polarized light

• Amyloid deposits often form rings around cardiac myocytes and capillaries.

• Intramural arteries and arterioles may have sufficient amyloid in their walls to compress and occlude their lumens, inducing myocardial ischemia (“small-vessel disease”).

Pericarditis

• Diseases of the pericardium include inflammatory conditions and effusions.

• Isolated pericardial disease is unusual, and pericardial lesions are almost always associated with disease in other portions of the heart or surrounding structures, or are secondary to a systemic disorder.

Pericarditis

• Primary pericarditis is uncommon.• In most cases it is caused by infection.

– Viruses, bacteria and fungi– Secondary to acute MI, cardiac surgery, irradiation to

the mediastinum, or processes involving other thoracic structures (e.g., pneumonia or pleuritis).

– Uremia is the most common systemic disorder associated with pericarditis.

– Rheumatic fever, SLE, and metastatic malignancies.

Morphology

Fibrinous pericarditis (uremia): an irregular appearance to the pericardial surface (so-called bread-and-butter pericarditis).

Fibrinopurulent (in acute bacterial pericarditis):Areas of frank pus;

Tuberculous pericarditis: areas of caseation.

Chronic pericarditis: The appearance of chronic pericarditis ranges from delicate adhesions to dense, fibrotic scars that obliterate the pericardial space. In extreme cases the heart is so completely encased by dense fibrosis that it cannot expand normally during diastole, so-called constrictive pericarditis.

Clinical Features

• Atypical chest pain, not related to exertion and often worse on reclining, and a prominent friction rub.

• • When associated with significant fluid accumulatio

n, acute pericarditis can cause cardiac tamponade, with declining cardiac output and shock.

• Chronic constrictive pericarditis produces a combination of right-sided venous distention and low cardiac output, similar to restrictive cardiomyopathy.

• Cardiomyopathies

Cardiomyopathies

• The cardiomyopathies are a group of diseases that primarily affect the heart muscle and are not the result of congenital, acquired valvular, hypertensive, coronary arterial, or pericardial abnormalities

• Primary cardiomyopathies -confined to the heart muscle

• Secondary cardiomyopathies -myocardial involvement as a component of a systemic or multiorgan disorder.

Classification of cardiomyopathies

• Primary myocardial involvement

1. Idiopthic (D,R,H)

2. Familial (D,R,H)

3. Eosinophilic endomyocardial disease (R)

4. Endomyocardial fibrosis (R)

Secondary myocardial involvement

• CARDIAC INFECTIONS  – Viruses, Chlamydia; Rickettsia; Bacteria; Fun

gi; Protozoa

• TOXINS  – Alcohol, Cobalt, Catecholamines, CO, Lithium,

Hydrocarbons, Arsenic, Cyclophosphamide, Doxorubicin and daunorubicin

• METABOLIC – Hyperthroidism, Hypothyroidism, Hyperkalemi

a, Hypokalemia, Nutritional deficiency (protein, thiamine, other avitaminoses), Hemochromatosis

• NEUROMUSCULAR DISEASE  – Friedreich ataxia, Muscular dystrophy, Conge

nital atrophies

• STORAGE DISORDERS AND OTHER DEPOSITIONS  – Hunter-Hurler syndrome, Glycogen storage disease, Fa

bry disease, Amyloidosis

• INFILTRATIVE  – Leukemia, Carcinomatosis,Sarcoidosis, Radiation-indu

ced fibrosis

• IMMUNOLOGICAL  – Myocarditis (several forms) , Post-transplant rejection

Clinical Classification of Cardiomyopathies

• Dilated: Left and/or right ventricular enlargement, impaired systolic function, congestive heart failure, arrhythmias, emboli

• Restrictive: Endomyocardial scarring or myocardial infiltration resulting in restriction to left and/or right ventricular filling

• Hypertrophic: Disproportionate left ventricular hypertrophy, typically involving septum more than free wall, with or without an intraventricular systolic pressure gradient; usually of a nondilated left ventricular cavity

Diagnosed as an isolated finding or associated with other congenital heart anomalies

DILATED CARDIOMYOPATHY (DCM)

• Progressive four chamber hypertrophy and dilation

• Contractile (systolic) dysfunction

• Can occur at any age

• Slow progressive to CHF.

• It is sometimes called congestive cardiomyopathy.

Pathogenesis

• Genetic influence

• Various acquired myocardial insults

• Myocarditis

• Alcohol or other toxicity

• Pregnancy associated.

Genetic influences

• 20%- 50% - is familial and caused by inherited genetic abnormalities.

• Autosomal-dominant inheritance is the predominant pattern

• Most commonly affect genes that encode cytoskeletal proteins (dystrophin). Duchene and Beker MD

• Mutation in enzyme involved in beta-oxidation of fatty acid

• Myocarditis (postviral). – DCM is a consequence of myocarditis.

• Alcohol and other toxins

– No morphologic features serve to distinguish alcoholic cardiomyopathy from DCM of other etiologies.

– Chronic alcoholism may be associated with thiamine deficiency.

Morphology

• The histologic abnormalities in DCM are nonspecific and usually do not point to a specific etiologic agent.

• Heart is usually enlarged, heavy (>2-3X), and flabby

• Mural thrombi are common• No primary valvular alterations• Most muscle - are hypertrophied with enlarged nuc

lei• Some are attenuated, stretched, and irregular. • Interstitial and endocardial fibrosis –present

Clinical Features• May occur at any age ( common 20 –50yrs). • CHF • MR & Arrhythmias• Ejection fractions < 25% • 50%- die within 2 years• 25% survive > 5 years• Death - cardiac failure or arrhythmia• Embolism from dislodgment of an intracardiac thrombus ca

n occur. • Cardiac transplantation is frequently done,

HYPERTROPHIC CARDIOMYOPATHY

• Characterized by myocardial hypertrophy, abnormal diastolic filling and in 1/3 cases-intermittent ventricular outflow obstruction.

• The heart is thick-walled, heavy, and hypercontracting

• Causes primarily diastolic dysfunction; systolic function is usually preserved.

Pathogenesis

• Mutations of genes encoding sarcomeric proteins.

• Mutations - gene encoding β-myosin heavy chain (β-MHC, cardiac TnT, α-tropomyosin, and myosin-binding protein C (MYBP-C)

Morphology

• Massive myocardial hypertrophy, without ventricular dilation

• Classic pattern is disproportionate thickening of the ventricular septum as compared with the free wall of the left ventricle

• On cross-section- “banana-like” left ventricle

• Histologic Features –– Extensive myocyte hypertrophy to a degree unusual i

n other conditions, with transverse myocyte diameters frequently greater than 40 μm (15 μm);

– Haphazard disarray of bundles of myocytes, individual myocytes, and contractile elements in sarcomeres within cells (termed myofiber disarray)

– Interstitial and replacement fibrosis

Clinical Features

• Exertional dyspnea

• Systolic ejection murmur

• Atrial fibrillation

• Mural thrombus formation

• Ventricular arrhythmias

• Sudden

RESTRICTIVE CARDIOMYOPATHY

• Characterized by primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole.

• May be idiopathic or associated with distinct diseases - principally radiation fibrosis, amyloidosis, sarcoidosis, metastatic tumors, inborn errors of metabolism.

Morphology

• Ventricles are of normal size or slightly enlarged

• Cavities are not dilated

• Myocardium is firm and noncompliant

Microscopy:

• May be only patchy or diffuse interstitial fibrosis

• Endomyocardial fibrosis - disease of children and young adults

• Fibrous tissue markedly diminishes the volume and compliance of affected chambers - induces a restrictive functional defect.

• Ventricular mural thrombi sometimes develop,