Myocarditis

INTRODUCTIONAs early as 1806 , a persistent inflammatory process following such an infection (eg, diphtheria) of the myocardium led to progressive cardiac damage and dysfunctionIn 1837, the term myocarditis was first introduced as inflammation or degeneration of the heart by postmortem Endomyocardial biopsy in 1980 allows the sampling of human myocardial tissue during life and antemortem diagnosis of myocarditis.

INTRODUCTIONStudies suggest that myocarditis is a major cause of sudden(20%), unexpected death in adults less than 40 years of ageProspective and retrospective studies have identified myocardial inflammation in 1 to 9 percent of routine postmortem examinations.

CAUSATION A large variety of infections, systemic diseases, drugs, and toxins have been associated with the development of this diseaseViruses, bacteria, protozoa, and even worms have been implicated as infectious agents.

PathophysiologySeveral mechanisms of myocardial damage (1) Direct injury of myocytes by the infectious agent (2) Myocyte injury caused by a toxin such as that from Corynebacterium diphtheriae (3) Myocyte injury as a result of infection- induced immune reaction or autoimmunity.

PathophysiologyTriphasic disease process Phase I: Viral Infection and Replication Phase 2: Autoimmunity and injury Phase 3: Dilated Cardiomyopathy

Phase I: Viral Infection and ReplicationCoxsackievirus B3 causes an infectious phase, which lasts 7-10 days, and is characterized by active viral replication During this phase initial myocyte injury takes place, causing the release of antigenic intracellular components such as myosin into the bloodstream

Phase 2: Autoimmunity and injury

The local release of cytokines, such as interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor (TNF), and nitric oxide may play a role in determining the T-cell reaction and the subsequent degree of autoimmune perpetuation These cytokines may also cause reversible depression of myocardial contractility without causing cell death.

Phase 2: Autoimmunity and injuryImmune-mediated by CD8 lymphocytes and autoantibodies against various myocyte components Antigenic mimicry, the cross reactivity of antibodies to both virus and myocardial proteins Myocyte injury may be a direct result of CD8 lymphocyte infiltration

Phase 3: Dilated CardiomyopathyViruses may also directly cause myocyte apoptosis.During the autoimmune phase, cytokine activate the matrix metalloproteinases, such as gelatinase, collagenases, and elastases.In later stages of immune activation, cytokines play a leading role in adverse remodeling and progressive heart failure.Cardiomyopathy developed despite the absence of viral proliferation but was correlated with elevated levels of cytokines such as TNF.

Clinical Findings Symptoms and Signs - Patients(59%) frequently present days to weeks after an acute febrile illness, particularly a flu-like syndrome - Myocarditis is most commonly asymptomatic, with no evidence of left ventricular dysfunction - fever, malaise, fatigue, arthralgias, myalgias, and skin rash. -Cardiac symptoms may result from systolic or diastolic left ventricular dysfunction or from tachyarrhythmias or bradyarrhythmias (dyspnea, fatigue, decreased exercise tolerance, palpitations )

Clinical FindingsSymptoms and Signs - Chest discomfort(35%) is a common symptom and is typically pericardial in nature - Myocarditis may present as sudden death, as a result of malignant ventricular arrhythmias or complete heart block -Systemic and pulmonary thromboemboli have also been noted.

Clinical FindingsPhysical Examination -Tachycardia, hypotension, fever and tachycardia may be disproportionate to the degree of fever -Bradycardia is seen rarely, and a narrow pulse pressure is occasionally detected -Murmurs of mitral or tricuspid regurgitation are common , S3 and S4 gallops may also be heard. -Distended neck veins, pulmonary rales, wheezes, gallops, and peripheral edema may be detected

Diagnostic Studies Electrocardiography -The most common abnormality is sinus tachycardia. - may show ventricular arrhythmias or heart block, or it may mimic the findings in acute myocardial infarction or pericarditis. -Relations between these clinical and laboratory findings

Diagnostic StudiesChest radiograph -Mild to moderate cardiomegaly from dilatation of the left or right ventricular cavity -The cardiac silhouette may also be globular when a pericardial effusion is present - Venous congestion and pulmonary edema may be seen in more severe cases

Diagnostic StudiesEchocardiography -myocardial contractility , chamber sizes , valvular function -Left ventricular systolic dysfunction, regional wall motion abnormalities , global hypokinesis - LV may be normal in size or minimally enlarged -Mitral or tricuspid regurgitation -Mural thrombi in 15% of cases

Diagnostic Studies -helpful in demonstrating abnormalities of diastolic filling that mimic restrictive cardiomyopathy and indistinguishing ventricular dilatation from pericardial effusion -monitor the course of the illness and to evaluate therapy Radionuclide ventriculography -provides accurate estimates of chamber volumes, as well as left and right ventricular ejection fractions

Diagnostic Studies Myocardial imaging -Gallium-67 imaging -> active inflammation of the myocardium and pericardium -Indium-111 monoclonal antimyosin antibody imaging -> detecting myocyte injury in patients -Contrast media-enhanced MRI ->detecting myocardial inflammation

Diagnostic Studies Cardiac catheterization -elevated left ventricular end-diastolic pressure, a depressed cardiac output, and increased ventricular volumes -Coronary angiogram typically demonstrates normal coronary arteries.

Diagnostic StudiesEndomyocardial biopsy - gold standard for the diagnosis of myocarditis -Dallas criteria (an inflammatory infiltrate of the myocardium +injury to the adjacent myocytes) -borderline myocarditis is made when the infiltrate is not accompanied by myocyte injury

Normal Myocardium

Borderline Myocarditis

Active Myocarditis

Others test elevated erythrocyte sedimentation rate (ESR) , mild to moderate leukocytosis CPK-MB , Cardiac troponin-I Other laboratory analyses that may be useful include a Mono-spot test, Epstein-Barr virus titers, hepatitis serology, and urine and serum for cytomegalovirus (CMV).

Triphasic disease process.

ReferencesAdvances in the understanding of myocarditis. Circulation 2001;104:1076. Feldman AM, McNamara D: Myocarditis. N Engl J Med 2000;19:1388. Diagnosis and presentation of fatal myocarditis Human Pathology (2005) 36, 1003 1007