The role of genetics in the prognosis of acute myocarditis: a systematic review and meta-analysis.

Myocarditis is a heterogeneous disease with varying clinical presentations, etiologies, and courses. Apart from environmental factors, genetic factors may also play a role in its pathophysiology. Through a systematic review and meta-analysis, we aimed to characterize the relationship between acute myocarditis (AM), underlying genetic background, and prognosis. We searched on MEDLINE/PubMed and Web of Science for studies reporting clinical outcomes of patients presenting with AM and undergoing genetic testing. The prevalence of a positive genetic test result was 27.3%, with a higher proportion of males (61.3%). Patients with a positive genetic test often had a family history of cardiovascular events (53.3%) and late gadolinium enhancement on cardiac magnetic resonance (81.2%), suggesting that these clinical features may represent a population with a higher burden of genetic background and risk for worse outcomes. The risk of recurrence of AM among patients with a positive genetic test was four times greater than among non-carriers (RR=4.02, p<0.001), and the most frequently observed variants among AM carriers were in the TTN, DSP, PKP2, MYH7, BAG3, RMB20, DSG2, TNNT2, and SCN5A genes. Overall, these findings underscore the need to improve the criteria used for genetic testing in the setting of AM episodes and to identify affected individuals who may benefit from increased surveillance and genetic testing.