Description

Myocarditis is defined as an inflammatory disease of heart muscle, diagnosed by histologic and/or immunologic examination. The associated myocardial dysfunction can cause varying clinical manifestations, ranging from minimal cardiac symptoms to severe heart failure, arrhythmias, and sudden death.

Epidemiology

• Prevalence of clinical myocarditis is estimated at 5.5 per 10,000 adults, with further estimates difficult to ascertain given variation in clinical severity with subacute presentation, as well as various etiologies and underdiagnosis.
• There is a bimodal age distribution with highest rates of diagnosis in infants <1 year of age and in ages 14 to 18 years.

Risk Factors

• Exposure to infectious agents (mainly viruses), drugs, toxins, and systemic diseases
• Autoimmune disease
• Systemic disease

Pathophysiology

• Pathophysiology of myocarditis may vary based on cause (see “Etiology”).
• Viral myocarditis is best characterized and involves a complex interaction among the virus, host immune response, and environmental factors. Three stages include (i) viral injury and innate immune response, (ii) acquired host immune response, and (iii) recovery or chronic cardiomyopathy.
• Inflammatory response from innate and acquired immune response may result in significant damage to the myocardium and conduction system.
• Development of autoantibodies may also play a key role in acute and chronic myocardial damage.
• Virus may cause direct damage to the myocardium independent of inflammation, secondary to cleavage of structural proteins.
• Pathogenesis of nonviral myocarditis is poorly understood.
• Regardless of the cause, symptom severity increases with worsening ventricular function and/or with worsening arrhythmias.
• Fulminant myocarditis may be characterized by both severe systolic and diastolic dysfunction.
• Progressive left ventricular systolic dysfunction may lead to hypotension, acidosis, and end-organ dysfunction.
• Left ventricular diastolic dysfunction may result in elevated left ventricular end diastolic pressures, leading to pulmonary venous and arterial hypertension, with concomitant pulmonary edema and right-sided heart failure.

Etiology

• Causes include infection, toxins, drugs, autoimmune disease, and systemic disease.
• Infectious causes include viral, bacterial, rickettsial, fungal, helminthic, spirochetal, and protozoal agents.
• Viral infection is the most common in developed countries including enteroviruses (e.g., coxsackievirus), erythroviruses (e.g., parvovirus B19), adenoviruses, herpes viruses (e.g., human herpesvirus 6 [HHV-6], Epstein-Barr virus [EBV], cytomegalovirus [CMV]), as well as hepatitis C. Both RNA and DNA viruses have been implicated. The last 20 years has seen a shift in viral etiology: from more cases with enteroviruses and adenoviruses to more frequent parvovirus and HHV-6.
• Nonviral infectious causes are far less common but must be considered especially in endemic areas, such as Central and South America where Chagas disease is prevalent.
• Nonviral myocarditis may be secondary to exposure to chemicals (arsenic and hydrocarbons), alcohol, radiation, drugs (chemotherapeutics), as well as drug hypersensitivity, autoimmune disease such as systemic lupus erythematosus, or systemic disease such as Churg-Strauss or sarcoidosis.
• Giant cell myocarditis is a very rare form of myocarditis in children that is associated with autoimmune disease and drug hypersensitivity. These patients respond poorly to typical care and frequently require cardiac transplantation.