• New congestive heart failure with a history of an antecedent viral syndrome.
  
• Elevated cardiac biomarkers.
  
• Electrocardiogram shows sinus tachycardia, nonspecific ST-T changes, atrial or ventricular arrhythmias, or conduction abnormalities.
  
• Echocardiogram demonstrates chamber enlargement, wall motion abnormalities, systolic or diastolic dysfunction, or mural thrombi.
  
• Endomyocardial biopsy reveals an inflammatory infiltrate with adjacent myocyte injury.

Myocarditis is defined simply as an inflammatory process with necrosis that involves the myocardium. In the past, the myocardial injury was believed to be a direct result of the cytotoxic effects of the relevant organisms. Even as early as 1806, however, it was thought that a persistent inflammatory process following such an infection (eg, diphtheria) of the myocardium led to progressive cardiac damage and dysfunction. When the term “myocarditis” was first introduced in 1837 as inflammation or degeneration of the heart, the diagnosis could be made only postmortem. Fortunately, endomyocardial biopsy now allows the sampling of human myocardial tissue during life and thus the accurate antemortem diagnosis of myocarditis.

The histologic hallmark of myocarditis is a focal patchy or diffuse inflammatory infiltrate with adjacent myocyte injury. The inflammation may not be restricted to the myocardium but may also involve the adjacent endocardium, pericardium, and valvular structures.

Myocarditis is most commonly initiated by viral infection (Table 25–1). Initiation of the pathophysiologic abnormalities, however, may result from a variety of insults, including drugs, toxins, hypersensitivity reactions, collagen vascular diseases, and autoimmune reactions. The most common viruses associated with myocarditis in the United States and Western Europe in immunocompetent persons are adenoviruses, coxsackievirus B (enterovirus), parvovirus B19, herpes simplex, influenza A, and cytomegalovirus (CMV). Other viruses, bacteria, rickettsiae, spirochetes, fungi, protozoans, or metazoans can also produce myocarditis; such causes are uncommon, however (see Table 25–1). Successful identification of the most common offending pathogens depends on knowledge of the geographic region’s relevant endemic and epidemic infectious diseases, the person’s immunization status and immunocompetence, and the sophistication and availability of public health services.

Several mechanisms of myocardial damage have been proposed. (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.

The autoimmunity hypothesis is the most widely accepted theory. It is believed that the viral infection triggers a cell-mediated immunologic response that ultimately causes myocardial injury; the myocardial injury persists despite viral clearance.

In the murine model, 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. Subsequently, after viral clearance, a second phase of myocyte damage will start. This phase is immune-mediated by CD8 lymphocytes and autoantibodies against various myocyte components. Antimyosin antibodies were isolated from mice that developed myocarditis following coxsackievirus B infection, as well as from patients with myocarditis. Antigenic mimicry, the cross reactivity of antibodies to both virus and myocardial proteins, occurs when an infectious agent shares an identical antigen with the normal myocyte. This mechanism is documented in animal models, and it may play a role in humans. Myocyte injury may be a direct result of CD8 lymphocyte infiltration. 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.

The popularity of the autoimmune hypothesis deemphasizes the role of the virus. Animal studies show, however, that viral proliferation itself might cause myocarditis. Some studies demonstrate the persistence of viral genomic fragments in myocardial cells of patients with active myocarditis and in some patients with dilated cardiomyopathy. Although these fragments may not be infectious, viral RNA may still serve as a persistent antigen to drive the immunologic response.

Exposure to cardiotropic viruses, presumably followed by a viral infection of the myocardium, is common. Based on the detection of serum antibodies to cardiotropic viruses, approximately 70% of the adult population has had prior exposure. Nonetheless, resultant abnormalities in cardiac function or symptomatic heart failure are unusual. The host factors predisposing to these deleterious immune responses are as yet undefined. Immunocompromised patients, such as pregnant women and patients with acquired immunodeficiency syndrome (AIDS), are predisposed to myocarditis. The susceptibility to viral myocarditis may also be age-related or, based on familial occurrence, genetically predetermined.

Symptoms & Signs

Myocarditis is most commonly asymptomatic, with no evidence of left ventricular dysfunction. The clinical manifestations of myocarditis are protean, when they are present. Myocardial involvement may be overshadowed or completely masked by the constitutional symptoms of the illness or other organ dysfunction. Cardiac symptoms may result from systolic or diastolic left ventricular dysfunction or from tachyarrhythmias or bradyarrhythmias. Patients frequently seek medical attention days to weeks after an acute febrile illness, particularly a flu-like syndrome. Common constitutional symptoms include fever, malaise, fatigue, arthralgias, myalgias, and skin rash.

Chest discomfort is a common symptom and is typically pericardial in nature; ischemic or atypical pain may also occur. Occasionally, patients have the syndrome of acute myocardial infarction with ischemic chest pain, electrocardiographic (ECG) abnormalities, elevated cardiac isoenzymes, or evidence of left ventricular wall motion abnormalities. Viral coronary arteritis and vasospasm have been implicated as the cause of this syndrome, but the epicardial coronary arteries are usually widely patent.

The acute onset of symptoms of congestive heart failure in a young person or in a patient without known coronary artery disease often suggests the diagnosis of myocarditis. Classic symptoms of congestive heart failure, including dyspnea, fatigue, decreased exercise tolerance, palpitations, and right heart failure, may be present. This constellation of signs and symptoms may be indistinguishable from dilated cardiomyopathy. It should be noted that because the metabolic demands on the heart associated with fever or a viral illness may initiate the first episode of congestive heart failure in patients with asymptomatic left ventricular dysfunction or reduced cardiac reserve, heart failure following a viral syndrome does not necessarily imply myocarditis.

Patients may also present with other symptoms that have been described in myocarditis: dizziness, syncope, or palpitations caused by atrial and ventricular arrhythmias and conduction disturbances. 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.

Physical Examination

The findings on physical examination vary widely. The patient may appear ill because the other manifestations of a viral illness dominate the clinical picture, and myocardial involvement may become evident only later in the course of the illness. Preexisting heart disease can also obscure the findings of myocarditis on examination.