Genetic testing in consecutive cases of acute and clinically suspected myocarditis with noise in the family

Abstract Background Myocarditis is increasingly associated with dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Purpose The aim of our study was to define if a genetic predisposition exists in cases of myocarditis with suspicious findings of inherited cardiovascular disease (noise) in the family. Methods Consecutive patients referred to our unit from 2010 to 2021, with a presentation of acute or clinically suspected myocarditis, as defined by current criteria, went through family screening of the first and second-degree relatives. Patients fulfilling typical criteria for definite ARVC upon presentation were excluded. Patients with suspicious familial findings (familial noise) including a. family history of sudden cardiac death, b. family history of myocarditis or cardiomyopathy or c. findings suggestive of cardiac disease in the relatives (ECG abnormalities, complex or frequent ventricular arrhythmias, conduction disease, troponemia, structural abnormalities suggestive of cardiomyopathy) went through genetic analysis for 90 genes associated with cardiomyopathy. Results Fifty-five patients with myocarditis and familial noise were included (Table 1). In 49 (89%) patients ≥2 diagnostic criteria for clinically suspected myocarditis were fulfilled. In 50% of the patients, the noise in the family was revealed upon familial screening as there was no relevant family history. Myocardial inflammation was confirmed in 16 (29%) patients with histological findings on endomyocardial biopsy or ≥2 Lake Louise Criteria on cardiac magnetic resonance. Pathogenic or likely pathogenic variants were identified in 78% of the cases (figure 1). Desmoplakin (24%) followed by lamin A/C (13%) and titin (9%) were the most common genes identified. In cases with confirmed myocardial inflammation the genetic yield increased to 87%. Conclusions A significant proportion of myocarditis patients with “familial noise” carry a pathogenic genetic variant in a cardiomyopathy related gene. These findings potentially affect the clinical management and need for family and genetic screening in patients with clinically suspected myocarditis. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Greek Network for Precision Medicine in Cardiology and the Prevention of Sudden Cardiac Death in the Young, icardiacnet