Prevalence of Pathogenic Variants in Cardiomyopathy-Associated Genes in Acute Myocarditis: A Systematic Review and Meta-Analysis

Abstract

Background: Acute myocarditis is an inflammatory condition that may precede the development of dilated or arrhythmogenic cardiomyopathy.

Objectives: The aim of this study was to investigate the reported prevalence of pathogenic or likely pathogenic (P/LP) variants in cardiomyopathy-associated genes in patients with acute myocarditis.

Methods: For this systematic review and meta-analysis, the PubMed and Embase databases were searched on March 4, 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: 1) complicated myocarditis (ie, presenting with acute heart failure, reduced left ventricular ejection fraction, or life-threatening ventricular arrhythmias); and 2) uncomplicated myocarditis. The study was registered with the International Prospective Register of Systematic Reviews (CRD42023408668) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 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. For uncomplicated myocarditis, the pooled prevalence was 4.2% (95% CI: 1.8%-7.4%; I² = 1.4%), whereas for complicated myocarditis, the 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%), whereas 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.

Keywords: cardiomyopathy; genetics; myocarditis.