Chapter 41: Myocarditis and Pericarditis

MYOCARDITIS

DEFINITIONS AND EPIDEMIOLOGY

Myocarditis is an inflammatory disease of the myocardium diagnosed by established histological, immunological, and immunohistochemical criteria.^1,2 Myocarditis represents a spectrum of disease that may present as acute fulminant myocarditis and result in dilated cardiomyopathy (DCM). Despite advances in diagnostic and therapeutic options, myocarditis remains challenging, as the clinical presentation may range from the asymptomatic patient to the patient with fulminant heart failure and circulatory collapse, making the disease a diagnostic challenge. Pericarditis, or inflammation of the pericardium, may occur with myocarditis or in isolation.

Myocarditis is a global disease. In adults, myocarditis is thought to be responsible for 10-50% of newly diagnosed DCM.³ The annual incidence of myocarditis in children in the United States is thought to be 1 per 100,000 children with a prevalence of ~1 per 10,000.⁴ The annual incidence of myocarditis in the general population is ~0.05–0.1%.^5,6 The actual incidence of this clinically heterogeneous disease is likely much higher than this estimate due to unrecognized cases. The most common causes of myocarditis are infectious in nature, specifically viral, although other etiologies are well described. Unfortunately, a specific etiology is identified in fewer than half of the cases.⁷ With this in mind, suspected myocarditis may be deemed idiopathic in nature. Herein, we will describe the pathogenesis, diagnosis, and treatment of myocarditis and pericarditis.

PATHOGENESIS

The pathogenesis of the myocarditis depends on the etiology. We will focus on viral myocarditis, as viruses are the most common causes of myocarditis and the pathogenesis is relatively well understood, especially for enteroviruses (most commonly coxsackie B virus) and parvovirus B19. Nonviral causes of myocarditis include bacterial and other infectious causes, autoimmune disease, toxins and exposures, and hypersensitivity reactions. Our current understanding of the pathogenesis of viral myocarditis comes from animal models. Three stages have been identified: (1) viral entry and activation of the innate immune response, (2) activation of an acquired immune response, and (3) recovery or disease progression (Figure 41-1).⁸

In acute viral myocarditis, genomic material (DNA or RNA) from cardiotropic viruses enters the myocytes through endocytosis and produces viral proteins that activate innate immune cascades in the host. Inflammatory cellular infiltration with macrophages and natural killer cells enhances expression of inflammatory cytokines, specifically interleukin IL1, IL2, tumor necrosis factor (TNF), and interferon-γ as well as induction of cytokine mRNA, resulting in further inflammatory cell recruitment.^9,10 These cytokines activate inducible nitric oxide synthase in cardiac myocytes.¹¹

In part, the host immune response to myocarditis in addition to other inflammatory diseases, results in autoimmune activation and autoantibody production by B cells.¹² Damage to cardiomyocytes may result in the release of cardiac proteins ...