Impact of high intensity and long duration exercise in genetic arrhythmogenic left ventricular cardiomyopathy

Abstract

Abstract Background Arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) is a genetic disease associating extensive LV myocardial fibrosis with or without dysfunction and no or mild right ventricle (RV) involvement, at risk of life-threatening ventricular arrhythmias (VA). While high intensity (HI) and long duration (LD) exercise has been identified as a precipitating factor of RV dysfunction and VA in arrhythmogenic RV cardiomyopathy including in asymptomatic genetic variant carriers, the impact of exercise on disease phenotype and risk is not known in ALVC. Objective To study the relationship between practicing HI and LD exercise and the risk of developing an ALVC phenotype and its severity. Methods In a monocentric retrospective observational study, patients with a pathogenic variant in common ALVC genes (DSP, FLNC, DES, PLN, RBM20, TMEM43), including asymptomatic carriers without ALVC phenotype, were interviewed about their physical practice from age 7 to the time of genetic or disease diagnosis. Intensity and weekly duration of each activity were reported. HI and LD exercise were defined as having practiced at least 1 sport with an intensity ≥ 6 METs and ≥ 2.5 hours/week respectively. We studied the association of HI and LD exercise practice with the risk of ALVC phenotype occurrence and its severity, derived from clinical, ECG and imaging data. Results 114 out of 128 eligible patients answered the questionnaire and were included (85 (74.6%) with a DSP variant, 22 FLNC (19.3%), 6 DES (5.3%), 1 RBM20 (0.9%)). 35 were probands (31%) and 79 relatives (69%) among 46 families. 31 (27%) had no ALVC phenotype at the time of genetic diagnosis. Mean age at diagnosis was 41±18. 62 (54%) patients were women. 97 (85%) had practiced at least one sport, among which 81 (83.5%) at HI and 79 (81.4%) of LD. Median lifetime exercise dose was 18.5 MET.h/week. There were no differences in HI and LD exercise practice between probands and relatives (74.3% vs 69.6%, p=0.6 and 74.3% vs 67.1%, p=0.4 respectively), as well as between patients with and patients without ALVC phenotype at the time of diagnosis (74.7% vs 61.3%, p=0.2 and 72.3% vs 61.3%, p=0.3 respectively). Phenotypic features at diagnosis did not differ between patients with and without HI and LD practice (Table 1). Multivariate analysis adjusted on age and gender showed that HI and LD exercise were not significantly associated with an increased risk of developing an ALVC phenotype (Odds Ratio [95% confidence interval] for age, gender, HI and LD exercise were 1.03 [1.01-1.06] (p=0.013), 1.41 [0.58 ; 3.47] (p=0.45), 2.15 [0.63 ; 7.27] (p=0.22) and 1.17 [0.35 ; 3.87] (p=0.79) respectively). Phenotypic features at diagnosis did not differ across observed quartiles of lifetime exercise dose (Table 2). Conclusion Practicing HI and LD exercise was not associated with an increased risk of developing an ALVC phenotype and its severity at the time of diagnosis in genetic ALVC variant carriers.