Familial screening in case of acute myocarditis reveals inherited arrhythmogenic left ventricular cardiomyopathies

Abstract

Aims Several data suggest that acute myocarditis could be related to genetic variants involved in familial cardiomyopathies, particularly arrhythmogenic cardiomyopathy, but the management of patients with acute myocarditis and their families regarding their risk for having an associated inherited cardiomyopathy is unclear. Methods and results Families with at least one individual with a documented episode of acute myocarditis and at least one individual with a cardiomyopathy or a history of sudden death were included in the study. Comprehensive pedigree, including genetic testing, and history of these families were analysed. Six families were included. Genetic analysis revealed a variant in desmosomal proteins genes in all the probands [five in desmoplakin (DSP) gene and one in desmoglein 2 gene]. In the five families identified with a DSP variant, genetic testing was triggered by the association of an acute myocarditis with a single case of apparently isolated dilated cardiomyopathy or sudden death. Familial screening identified 28 DSP variant carriers; 39% had an arrhythmogenic left ventricular (LV) cardiomyopathy phenotype. Familial histories of sudden death were frequent, and a remarkable phenotype of isolated LV late gadolinium enhancement on contrast-enhanced cardiac magnetic resonance without any other structural abnormality was found in 38% of asymptomatic mutation carriers. None of the DSP variant carriers had imaging characteristics of right ventricle involvement meeting current Task Force criteria for arrhythmogenic right ventricular cardiomyopathy. Conclusions Comprehensive familial screening including genetic testing in case of acute myocarditis associated with a family history of cardiomyopathy or sudden death revealed unknown or misdiagnosed arrhythmogenic variant carriers with left-dominant phenotypes that frequently evade arrhythmogenic right ventricular cardiomyopathy Task Force criteria. In view of our results, acute myocarditis should be considered as an additional criterion for arrhythmogenic cardiomyopathy, and genetic testing should be advised in patients who experience acute myocarditis and have a family history of cardiomyopathy or sudden death.

Acute Myocarditis-Like Episode in a Curly-Haired Young Boy—Red Flags for Familial Arrhythmogenic Cardiomyopathy

“…These episodes may be recurrent, are frequently exercise-induced, and occur in the absence of any infectious triggers [ 5 , 7 ]. Conversely, genetic testing screening in six families, including patients with acute myocarditis associated with a family history of cardiomyopathy or SCD, revealed frequently arrhythmogenic variant carriers with left-dominant phenotypes, mainly with DSP variants [ 8 ]. While still considered rare in the ACM population, signs of acute myocarditis should draw the attention of the clinicians on this diagnostic possibility, especially when it occurs in relatives of patients with SCD, ventricular arrhythmia, or myocarditis history [ 9 ].…”

A case report of acute myopericarditis associated with Graves’ thyrotoxicosis

“…Desmoplakin genetic variants in particular have been noted in these patients and their relatives. Piriou et al 15 performed genetic analysis on families with a history of acute myocarditis for genetic variants known to be associated with AC. They reported several variants in this cohort relating to the desmoplakin gene.…”

Insights Into Genetics and Pathophysiology of Arrhythmogenic Cardiomyopathy

“…More recently, clinical reports of genetically proven ACM patients presenting with a clinical picture of acute myocarditis are suggesting that the disease may pass different phases [123]. The so-called hot phases are characterized by chest pain, ST-elevation, and troponin release [124].…”