Myocarditis

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Chapter 25

Myocarditis

1. What is myocarditis?

    Myocarditis is an inflammatory disease of the heart muscle that can cause acute heart failure, heart block, sudden death, and chronic dilated cardiomyopathy.

    Myocarditis can be classified by cause, histology, immunohistology clinicopathologic, and clinical criteria. The clinicopathologic classification consists of the following four categories:

Most myocarditis in developed countries results from a viral infection and the immune reaction to viral injury.

2. What is the pathogenesis of myocarditis?

    Most of the information about the pathogenesis of myocarditis derives from animal models rather than human studies. From these experiments, the progression from acute viral injury to chronic dilated cardiomyopathy can be simplified into a three-phase process:

image Phase 1, sometimes called acute viral, occurs after viral entry and proliferation in the myocardium and results in direct tissue injury even before an inflammatory reaction.

image Phase 2, called subacute immune, is characterized by activation of the innate and acquired immune response. The innate immune response leads to upregulation of a variety of inflammatory mediators like interferons, tumor necrosis factor, and nitric oxide, which ultimately result in an influx of tissue-specific T and B cells (acquired immune response) into the heart. If the inflammatory response persists, a chronic myopathic phase (phase 3) with fibrosis and remodeling with dilation of the ventricles may develop in susceptible individuals.

image In phase 3, immune activation may persist and contribute to progressive cardiomyopathy.

In any phase, inflammation and fibrosis may lead to ventricular arrhythmias or heart block.

3. What is the clinical presentation of myocarditis?

    The clinical presentation of myocarditis in adults is highly variable. Patients may report a viral prodrome of fever, rash, myalgias, arthralgias, fatigue, and respiratory or gastrointestinal symptoms in the days to weeks before cardiac symptoms, which range from mild dyspnea to chest pain and cardiogenic shock. Chest pain in myocarditis can mimic typical angina and be associated with electrocardiographic (ECG) changes, including ST segment elevation. There may be a rise in biomarkers of cardiac injury (e.g., troponins). The pattern of troponin elevation is typically longer than is seen following an acute coronary thrombosis. If the pericardium is involved, patients can present with symptoms typical of pericarditis. Cardiac rhythm disturbances are not uncommon and may include new-onset atrial or ventricular arrhythmias or high-grade atrioventricular (AV) block with syncope.

    In contrast to adults with myocarditis, children often have a more fulminant presentation and may require advanced circulatory support for ventricular failure in early stages of their disease. Despite a severe presentation, recovery after a period of hemodynamic support is not uncommon.

4. What is the incidence of myocarditis and who does it affect?

    The population-based incidence of myocarditis is not known because of the variable clinical presentation and lack of a specific, noninvasive diagnostic test. In referral cohorts of patients with otherwise unexplained acute to subacute heart failure, the incidence of biopsy-proven myocarditis is 9% to 10% using histologic criteria, and up to 40% using newer immunostain-based diagnostic standards. Recently, inflammation (using newer immunostains) has been observed in up to 40% of biopsies from patients with chronic, severe dilated cardiomyopathy.

    The mean age of adults diagnosed with myocarditis ranges from 20 to 51 years in most series. Most studies report a slight predominance of men, which may be partly mediated by testosterone. Testosterone increases post-viral inflammation in animal models of myocarditis. Myocarditis should be considered in select patients who develop cardiac symptoms and who also have risk factors for human immunodeficiency virus (HIV) infection, Chagas disease, and rheumatic fever.

5. What are the causative agents of myocarditis?

    Myocarditis can be triggered by many infectious pathogens, including viruses, bacteria, Chlamydia, rickettsia, fungi, and protozoans, as well as systemic toxic and hypersensitivity reactions (Table 25-1).

TABLE 25-1

CAUSES OF MYOCARDITIS

image

HIV, Human immunodeficiency virus.

∗Frequent cause of myocarditis.

From Elamm C, Fairweather D, Cooper LT: Pathogenesis and diagnosis of myocarditis, Heart 98:835-840, 2012.

    Viral infection is the most commonly reported cause of myocarditis in Western Europe and North America. Currently, the most commonly identified viruses in reports from Germany and the United States are parvovirus B19 and human herpesvirus 6 (HHV-6). Enteroviruses, in particular coxsackievirus B (CVB), were the most commonly identified viruses from the 1950s until the 1990s. CVB still causes regional clusters of myocarditis, although the overall reported rate of CVB infection had declined.

    Cytomegalovirus (CMV) can cause myocarditis in patients posttransplant and early infection posttransplant correlates with coronary allograft vasculopathy.

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