Prevalence of pathogenic variants in cardiomyopathy-associated genes in acute myocarditis: a systematic review and meta-analysis

Abstract

Abstract Background Acute myocarditis is an inflammatory condition that may precede the development of dilated or arrhythmogenic cardiomyopathy. Objectives To investigate the reported prevalence of pathogenic/likely pathogenic (P/LP) variants in cardiomyopathy-associated genes in patients with acute myocarditis. Methods For this systematic review and meta-analysis, we searched Pubmed and Embase databases on March 04, 2023. Observational studies evaluating the prevalence of P/LP variants in cardiomyopathy-associated genes in patients with acute myocarditis were included. Studies were stratified into adult and pediatric age groups and for the following scenarios: (a) complicated myocarditis (i.e., presenting with acute heart failure, reduced left ventricular ejection fraction, or life-threatening ventricular arrhythmias); (b) uncomplicated myocarditis. The study followed PRISMA guidelines. Results Of 732 studies identified, 8 met the inclusion criteria, providing data for 586 patients with acute myocarditis. A total of 89 P/LP variants in cardiomyopathy-associated genes were reported in 85 patients. In uncomplicated myocarditis the pooled prevalence was 4.2% (95% CI 1.8-7.4%, I2 1.4%), while in complicated myocarditis pooled prevalence was 21.9% (95% CI 14.3-30.5%, I2 38.8%) and 44.5% (95% CI 22.7-67.4%, I2 52.8%) in adults and children, respectively. P/LP variants in desmosomal genes were predominant in uncomplicated myocarditis (64%), while sarcomeric gene variants were more prevalent in complicated myocarditis (58% in adults and 71% in children). Conclusions Genetic variants are present in a large proportion of patients with acute myocarditis. The prevalence of genetic variants and the genes involved vary according to age and clinical presentation.Central Illustration