Acute myocarditis: the inherited view

Acute myocarditis is the second most common inflammatory disorder of the heart with an estimated annual incidence of approximately 22 cases/100,000 individuals in the general population/year. The diagnosis is established in the presence of well-defined histological, immunological and immunohistological criteria. Sudden cardiac death following malignant cardiac arrhythmias or cardiogenic shock in the acute phase and/or dilated cardiomyopathy (DCM) with heart failure development and need for transplantation in the long-run are the most fearful complications. The rate of progression to DCM is estimated at 6-30%. Acute myocarditis is considered as an unfortunate and random consequence of infectious, toxic, or autoimmune reactions targeting the myocardium.

The role of genetics factors in acute myocarditis and its progression to dilated cardiomyopathy is a subject of intense ongoing research. It is currently estimated that a genetic mutation is responsible for approximately 35% of dilated cardiomyopathy cases. Nonetheless apart from the genetic substrate of both host and inciting microbes, additional factors may have a role in acute myocarditis cases such as molecular mimicry between myocardial components and microbial proteins, in conjunction with environmental factors. Moreover, the notion of randomness in acute myocarditis susceptibility is additionally challenged by the acknowledgement that acute myocarditis is more common in individuals with genetically induced derangements in cardiomyocyte cytoskeletal components, including the dilated cardiomyopathy of Duchenne muscular dystrophy and arrhythmogenic cardiomyopathy. To assess the hypothesis that vulnerability to acute myocarditis is due to genetically mediated impairments in cardiomyocyte cytoskeletal structures caused by variants in ‘cardiomyopathy’ and ‘neuromuscular disorder’ genes, Kontorovich, AR et al. compared sequencing data for genes related to cardiomyocyte structure and function between patients with acute myocarditis and healthy control subjects. In this work putatively deleterious variants of cardiac genes have been found in 19 of 117 (16%) acute myocarditis cases vs 34 of 468 (7.2%) control subjects (P=0.003). Notably implicated genes were among those typically associated with cardiomyopathies and neuromuscular disorder with cardiac involvement, which implies shared pathways between acute myocarditis and the latter disorders. Clinical phenotypes did not correlate with genetic testing which is deemed accordingly indispensable to inform risk in relatives.

The key message of this work is that patients with acute myocarditis should be advised about the possible overlap of ‘myocarditis genes’ with cardiomyopathies and neuromuscular disorders which is important in terms of personal and family screening.