eMedicine Specialties > Cardiology > Myocardial Disease and Cardiomyopathies

Myocarditis

Author: Wai Hong Wilson Tang, MD, Assistant Professor of Medicine, Section of Heart Failure and Cardiac Transplantation Medicine, Cleveland Clinic Foundation
Contributor Information and Disclosures

Updated: Sep 2, 2008

Introduction

Background

Myocarditis is an inflammatory disease of the myocardium with a wide range of clinical presentation, from subtle to devastating. It is diagnosed by established histologic, immunologic, and immunochemical criteria. Myocarditis is described as "an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes."¹ It usually manifests in an otherwise healthy person and can result in rapidly progressive (and often fatal) heart failure and arrhythmia. In the clinical setting, myocarditis is synonymous with inflammatory cardiomyopathy.

Lieberman proposed the following alternative clinicopathologic classification:²

• Fulminant myocarditis - Follows a viral prodrome; distinct onset of illness comprising severe cardiovascular compromise with ventricular dysfunction and multiple foci of active myocarditis; either resolves spontaneously or results in death
• Acute myocarditis - Less distinct onset of illness, with established ventricular dysfunction; may progress to dilated cardiomyopathy
• Chronic active myocarditis - Less distinct onset of illness, with clinical and histologic relapses; development of ventricular dysfunction associated with chronic inflammatory changes (including giant cells)
• Chronic persistent myocarditis - Less distinct onset of illness; persistent histologic infiltrate with foci of myocyte necrosis without ventricular dysfunction despite symptoms (eg, chest pain, palpitations)

These terms are still used to describe the clinical presentation and progression of myocarditis, particularly in the absence of ongoing histologic evaluation.

For related information, see Medscape's Heart Failure and Cardiac Rhythm Management Resource Center.

Pathophysiology

Myocarditis is likely caused by a wide variety of infectious organisms, autoimmune disorders, and exogenous agents, with genetic and environmental predisposition. Most cases are presumed to be caused by a common pathway of host-mediated, autoimmune-mediated injury, although direct cytotoxic effects of the causative agent and damages due to cytokine expression in the myocardium may play some role in myocarditis etiology. Damage occurs through the following mechanisms:

• Direct cytotoxic effect of the causative agent
• Secondary immune response, which can be triggered by the causative agent
• Cytokine expression in the myocardium (eg, tumor necrosis factor-alpha, nitric oxide synthase)
• Aberrant induction of apoptosis

Myocardial damage has 2 main phases, as follows:

• Acute phase (first 2 wk): Myocyte destruction is a direct consequence of the offending agent, which causes cell-mediated cytotoxicity and cytokine release, contributing to myocardial damage and dysfunction. Detection of the causal agent is uncommon during this stage.
• Chronic phase (>2 wk): Continuing myocyte destruction is autoimmune in nature, with associated abnormal expression of human leukocyte antigen (HLA) in myocytes (and in the case of viral myocarditis, persistence of viral genome in myocardium).

In viral myocarditis, viral isolates differ in tissue tropism and virulence. For example, coxsackievirus A9 is a self-limiting myocarditis, whereas coxsackievirus B3 causes severe myocarditis resulting in a high mortality rate. The induction of the coxsackie-adenovirus receptor (CAR) and the complement deflecting protein decay accelerating factor (DAF, CD55) may allow efficient internationalization of the viral genome. Viral replication may lead to further disruption of metabolism and perturbation of inflammation and its response. Vasospasm induced by endothelial cell viral infection may also contribute to further damage.³

New evidence of dystrophin disruption by expression of enteroviral protease 2A points to yet another unique pathogenic mechanism.⁴ In contrast, some viruses (such as parvovirus B19) may focus on pericapillary depositions, contributing to diastolic dysfunction rather than direct myocyte destruction. Regardless, viral persistence provides the necessary stimuli for autoimmune or other inflammatory responses.

Frequency

United States

Frequency is difficult to ascertain, owing to the wide variation of clinical presentation. Incidence is usually estimated at 1-10 cases per 100,000 persons. Incidence of positive right ventricular biopsy findings in patients with suspected myocarditis is highly variable (ranging from 0-80%). According to estimates, as many as 1-5% of patients with acute viral infections may have involvement of the myocardium.

International

• A population study in Finland found that, in nearly a study of 700,000 healthy young male military recruits, 98 cases had myocarditis mimicking myocardial ischemia, 1 case presented as sudden death, and 9 cases presented as recent-onset dilated cardiomyopathy.⁵
• A Japanese 20-year series of 377,841 autopsies found idiopathic, nonspecific, interstitial, or viral myocarditis in only 0.11% of individuals.⁶

Mortality/Morbidity

Most patients with mild symptoms recover completely without any residual cardiac dysfunction, with a third subsequently developing dilated cardiomyopathy.^7,8,9

• In the Myocarditis Treatment Trial, the 1-year mortality rate was 20% and the 4-year mortality rate was 56% in a population with symptomatic heart failure presentation and left ventricular ejection fraction lower than 45% at baseline.¹⁰
• For untreated giant cell myocarditis, median survival from symptom onset is only 5.5 months, and the 1-year mortality rate is 80% (includes death and transplant).¹¹
• Mortality rate for postpartum cardiomyopathy at 1 year also can be as high as 50%.

Race

No particular predominance is noted except for peripartum cardiomyopathy (a specific form of myocarditis that appears to have a higher incidence in patients of African descent).

Sex

Incidence is similar between males and females, although young males are particularly susceptible.

Age

Patients are usually fairly young. The median age of patients affected with lymphocytic myocarditis is 42 years.

• Patients with giant cell myocarditis may be older (mean age 58 years), but this condition usually does not discriminate with respect to age, sex, or presenting symptoms.
• Other susceptible groups include immunocompromised individuals, pregnant women, and children (particularly neonates).

Clinical

History

Clinical history is of acute decompensation of heart failure in a person with no other underlying cardiac dysfunction or with low cardiac risk. The diagnosis is usually presumptive, based on patient demographics and the clinical course (eg, spontaneous recovery following supportive care).

• Patients may present with mild symptoms of chest pain (in concurrent pericarditis), fever, sweats, chills, and dyspnea.
• In viral myocarditis, patients may present with a history of recent (within 1-2 wk) flulike syndrome of fevers, arthralgias, and malaise or pharyngitis, tonsillitis, or upper respiratory tract infection.
• Population studies suggest that adults may present with few symptoms, rather than the acute toxic state of cardiogenic shock or frank heart failure (fulminant myocarditis) that is often associated with myocarditis.
• Symptoms of palpitations, syncope, or even sudden cardiac death may develop, due to underlying ventricular arrhythmias or atrioventricular block (especially in giant cell myocarditis).
• Adults may present with heart failure years after initial index event of myocarditis (as many as 12.8% of patients with idiopathic dilated cardiomyopathy had presumed prior myocarditis in one case series).

Physical

Patients with myocarditis usually present with signs and symptoms of acute decompensation of heart failure (eg, tachycardia, gallop, mitral regurgitation, edema) and pericardial friction rub in those with concomitant pericarditis. Specific findings in special cases are as follows:

• Sarcoid myocarditis - Lymphadenopathy, also with arrhythmias, sarcoid involvement in other organs (up to 70%)
• Acute rheumatic fever (usually affects heart in 50-90%) - Associated signs such as erythema marginatum, polyarthralgia, chorea, subcutaneous nodules (Jones criteria)
• Hypersensitive/eosinophilic myocarditis - Pruritic maculopapular rash and history of using offending drug
• Giant cell myocarditis - Sustained ventricular tachycardia in rapidly progressive heart failure¹²
• Peripartum cardiomyopathy - Heart failure developing in the last month of pregnancy or within 5 months following delivery

Causes

Approximately 50% of the time, myocarditis is classified as idiopathic, although a viral etiology is often suspected but unproved, even with sophisticated immunohistochemical and genomic studies. Recent studies on patients with idiopathic dilated cardiomyopathy found evidence of viral particles in endomyocardial biopsy specimens in up to two thirds of the patients.¹³

• Viral - Enterovirus, coxsackie B, adenovirus, influenza, cytomegalovirus, poliomyelitis, Epstein-Barr virus, HIV-1, viral hepatitis, mumps, rubeola, varicella, variola/vaccinia, arbovirus, respiratory syncytial virus, herpes simplex virus, yellow fever virus, rabies, parvovirus
• Rickettsial - Scrub typhus, Rocky Mountain spotted fever, Q fever
• Bacterial - Diphtheria, tuberculosis, streptococci, meningococci, brucellosis, clostridia, staphylococci, melioidosis, Mycoplasma pneumoniae, psittacosis
• Spirochetal - Syphilis, leptospirosis/Weil disease, relapsing fever/Borrelia, Lyme disease
• Fungal - Candidiasis, aspergillosis, cryptococcosis, histoplasmosis, actinomycosis, blastomycosis, coccidioidomycosis, mucormycosis
• Protozoal - Chagas disease, toxoplasmosis, trypanosomiasis, malaria, leishmaniasis, balantidiasis, sarcosporidiosis
• Helminthic - Trichinosis, echinococcosis, schistosomiasis, heterophyiasis, cysticercosis, visceral larva migrans, filariasis
• Bites/stings - Scorpion venom, snake venom, black widow spider venom, wasp venom, tick paralysis
• Drugs (usually causing hypersensitivity myocarditis)
  • Chemotherapeutic drugs - Doxorubicin and anthracyclines, streptomycin, cyclophosphamide, interleukin-2, anti-HER-2 receptor antibody/Herceptin
  • Antibiotics - Penicillin, chloramphenicol, sulfonamides
  • Antihypertensive drugs - Methyldopa, spironolactone
  • Antiseizure drugs - Phenytoin, carbamazepine
  • Amphetamines, cocaine, catecholamines
• Chemicals - Hydrocarbons, carbon monoxide, arsenic, lead, phosphorus, mercury, cobalt
• Physical agents (radiation, heatstroke, hypothermia)
• Acute rheumatic fever
• Systemic inflammatory disease - Giant cell myocarditis, sarcoidosis, Kawasaki disease, Crohn disease, systemic lupus erythematosus, ulcerative colitis, Wegener granulomatosis, thyrotoxicosis, scleroderma, rheumatoid arthritis
• Peripartum cardiomyopathy
• Posttransplant cellular rejection

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