Myocarditis

9 FEB 2010

 Myocarditis is an inflammatory disorder of the

myocardium with necrosis of the myocytes and associated inflammatory infiltrate.

CAUSATION
A large variety of infections, systemic diseases,

drugs, and toxins have been associated with the development of this disease Viruses, bacteria, protozoa, and even worms have been implicated as infectious agents.

Cause
Adenovirus and Ebstein-Barr virus parvovirus B19 and human herpesvirus-6 are the most frequent pathogens in patients with acute myocarditis.

Infecting organisms include Coxsackievirus types A and B (especially type B), Adenovirus (most commonly types 2 and 5),Cytomegalovirus, Echovirus, Epstein-Barr virus, Hepatitis C virus, Herpes virus, Human immunodeficiency virus, Influenza and parainfluenza , Measles, Mumps, associated with endocardial fibroelastosis (EFE) , Parvovirus B19, Poliomyelitis virus, Rubella, Varicella

Pathophysiology
Several 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 infectioninduced immune reaction or autoimmunity.

Pathophysiology
Triphasic disease process

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

Phase I: Viral Infection and Replication

Coxsackievirus 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 injury

Immune-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 Cardiomyopathy

Viruses 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
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

Clinical Finding (cardiac symptom)

Heart failure This is the most common presentation. Chest pain due to myocardial ischemia or concurrent pericarditis. Arrhythmia Atrioventricular conduction disturbances, Sinus tachycardia

Dilated cardiomyopathy

Initial symptoms in infants

Lethargy Irritability Periodic episodes of Oliguria elevated liver enzymes elevated BUN and

pallor Fever Hypothermia Tachypnea Anorexia Failure to thrive

creatinine levels caused by direct viral damage, low cardiac output

Physical sign
Infants Signs failure to thrive, anorexia, tachypnea, tachycardia, wheezing, and diaphoresis with feeding. In severe cases, low cardiac output may progress to acidosis and death. End-organ damage may develop because of direct viral infestation or because of low cardiac output. CNS involvement may also develop.

Investigation
CBC LDH CK-MB

Troponin I
Viral Titer PCR CXR

ECG
Low-voltage QRS (<5 mm throughout the limb leads) is the

classic pattern. Pseudoinfarction patterns with pathologic Q waves and poor progression of R waves in the precordial leads may also be present.T-wave flattening or inversion is a common finding associated with small or absent Q waves in V5 and V6.Left Ventricular hypertrophy with strain may be present. Other nonspecific findings include prolonged PR segment and prolonged QT interval. Sinus tachycardia Premature ventricular contractions and atrial tachycardias Junctional tachycardia Second-degree and third-degree atrioventricular block

Echocardiography
Global hypokinesis Increased left ventricular end diastolic and systolic

dimensions Left ventricular dysfunction, primarily systolic with decreased ejection fraction and shortening fraction Segmental wall motion abnormalities Pericardial effusion

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

Gold Standard diagnosis

Myocardial biopsy focal or diffuse interstitial infiltrate of mononuclear cells, lymphocytes, plasma cells, and eosinophils. Dallas criteria (an inflammatory infiltrate of the myocardium +injury to the adjacent myocytes)

Normal Myocardium

Borderline Myocarditis

Active Myocarditis

Treatment
Supportive treatment A low-salt diet is recommended for patients with congestive heart failure Bed rest is necessary during the acute phase of the illness and may slow the intramyocardial replication of the virus.

Treatment
Anticongestive Rapid-acting diuretics

furosemide or ethacrynic acid, 1 mg/kg, each one to three times a day dobutamine or dopamine, are useful in critically ill children. half of the usual digitalizing dose because some patients with myocarditis are exquisitely sensitive to the drug.

Rapid-acting inotropic agents

Digoxin may be given cautiously

Treatment
Immunosuppressive agents High-dose gamma globulin (2 g/kg, over 24 hours) associated with better survival during the first year after presentation The role of corticosteroids is unclear.

Prognosis
Studies give a wide spectrum of mortality and

morbidity statistics. With suspected coxsackievirus B, mortality rate is higher in newborns (75%) than in older infants and children (10-25%). Complete recovery of ventricular function has been reported in as many as 50% of patients. Some patients develop chronic myocarditis dilated cardiomyopathy, or both. Those who develop dilated cardiomyopathy may require a heart transplant.

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