Viral Myocarditis: From the Perspective of the Virus

Viral myocarditis has been recognized as a cause of congestive heart failure for >50 years, but it is still a challenging disease to diagnose and treat.1,2 The history and clinical features are often nonspecific, and practical serological markers are not available during the acute phase of the disease. Even after proper diagnosis, no clinically proven treatment exists to inhibit the development of subsequent dilated cardiomyopathy (DCM) and, in some cases, death. Accordingly, to facilitate future scientific work into this difficult clinical entity, this review proposes a clinical paradigm that focuses on the phases of viral infection and the molecular insights that are important for these phases of the infectious process with a focus on interactions between the virus and the cardiac myocyte. Myocarditis is defined as inflammation of the heart muscle. The gold standard for diagnosis has been the Dallas criteria based on histopathology from an endomyocardial biopsy.3 It is now recognized that the Dallas criteria are not sensitive for myocarditis because they do not consider the presence of viral genome in the heart.4 Furthermore, an invasive procedure is required to obtain a sample of the myocardium. Many viruses have been implicated as causes of myocarditis. These most commonly include adenoviruses and enteroviruses such as the coxsackieviruses. Recently, parvovirus B19 has been associated with a significant percentage of patients diagnosed with myocarditis and DCM.5 However, a growing body of data indicates that parvovirus is present in a large percentage of patients who do not have myocarditis.6–8 Of the viruses that cause myocarditis, the cellular and molecular mechanisms associated with coxsackieviral infection of the heart have been most thoroughly investigated with murine models. Therefore, the mechanistic experiments described in this review focus primarily, but not exclusively, on coxsackieviral myocarditis. It is important to note that coxsackieviruses …