Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5.
Arrhythmogenic right ventricular cardiomyopathy type V (ARVC-5) is the most aggressive heterozygous form of ARVC. It is predominantly caused by a fully penetrant mutation (p.S358L) in the nondesmosomal gene TMEM43-endemic to Newfoundland, Canada. To date, all familial cases reported worldwide share a common ancestral haplotype. It is unknown whether the p.S358L mutation by itself causes ARVC-5 or whether the disease is influenced by genetic or environmental factors. The purpose of this study was to examine the phenotype, clinical course, and the impact of exercise on patients with p.S358L ARVC-5 without the Newfoundland genetic background. We studied 62 affected individuals and 73 noncarrie…
Association of Left Ventricular Systolic Dysfunction Among Carriers of Truncating Variants in Filamin C With Frequent Ventricular Arrhythmia and End-stage Heart Failure
Importance: Truncating variants in the gene encoding filamin C (FLNCtv) are associated with arrhythmogenic and dilated cardiomyopathies with a reportedly high risk of ventricular arrhythmia.Objective: To determine the frequency of and risk factors associated with adverse events among FLNCtv carriers compared with individuals carrying TTN truncating variants (TTNtv).Design, Setting, and Participants: This cohort study recruited 167 consecutive FLNCtv carriers and a control cohort of 244 patients with TTNtv matched for left ventricular ejection fraction (LVEF) from 19 European cardiomyopathy referral units between 1990 and 2018. Data analyses were conducted between June and October, 2020.Main…