Impaired Cardiac Function in Viral Myocarditis

Abstract

Viral myocarditis, the inflammation of the myocardium caused by viral infection, is an important cause of dilated cardiomyopathy (DCM) – a major cause of morbidity and mortality worldwide (Mason, 2003; Esfandiarei & McManus, 2008; Cooper, 2009). In North America, viral myocarditis and DCM together account for 20% of the sudden deaths and heart failure in children and adolescents (Okuni et al., 1975; Drory et al., 1991). To date, there is no effective therapeutic against these diseases. Patients diagnosed with late stage DCM are limited to supportive treatments such as ventricular assist device implantation and heart transplantation. The clinical presentation of viral myocarditis comes in various severities. Most people have contracted and subsequently recovered from multiple viral infections of the heart without overt symptoms. Yet, retrospective studies revealed that ~20% of subclinical cases later develop congestive heart failure. In addition, some may experience acute fulminant viral myocarditis or persistent chronic myocarditis symptoms. About one-third of these patients with viral myocarditis subsequently develop DCM (Esfandiarei & McManus, 2008). A combination of new diagnostic technologies for viral myocarditis such as cardiovascular magnetic resonance techniques with conventional diagnostics including clinical presentation, histopathological examination, cardiac antibody assessment, and viral polymerase chain reaction (PCR), now helps better define disease stage and its respective management protocol (Baughman, 2006). The presence of viral genome in the myocardium is associated with significantly worse outcome over two years (Why et al., 1994). Analysis of human failing hearts by PCR unveiled trails of previous viral infection. The identified viruses include enterovirus, adenovirus, parvovirus B19, herpes simplex virus 6, cytomegalovirus, hepatitis C virus, and human immunodeficiency virus, which are clinically associated with viral myocarditis (Grist & Reid, 1997; Calabrese et al., 2010). Among them, coxsackievirus B3 (CVB3), an enterovirus in the picornavirus family, is highly implicated in clinical cases of viral myocarditis, particularly in neonates and young children, and is the most thoroughly studied causative agent in experimental viral myocarditis models (Froeschle et al., 1966; Abelmann, 1971; Reyes & Lerner, 1985; McManus et al., 1988). CVB3 replicates rapidly in short infection cycles that begin with viral receptor engagement and subsequent internalization, followed by translation of viral RNA, amplification of viral genome, viral assembly, and complete with viral progeny release.