Disease progression in exercise-induced compared to desmosomal arrhythmogenic cardiomyopathy - a longitudinal cohort study

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: Public hospital(s). Main funding source(s): Oslo University Hospital, Procardio Center for Innovation INTRODUCTION: Arrhythmogenic cardiomyopathy (AC) is an inheritable heart disease caused by mutations in genes encoding the cardiac desmosomes, while exercise-induced AC (EiAC) has been proposed as an acquired similar phenotype in athletes. Little is known about the progression of EiAC compared to AC. PURPOSE: To assess functional and structural disease progression in EiAC compared to desmosomal AC during long-term follow-up. METHODS: We consecutively included probands with definite AC diagnosis according to the 2010 Task Force Criteria and patients with EiAC in a longitudinal cohort study. EiAC was diagnosed in competitive endurance athletes (>24 MET-hours/week for >6 consecutive years) referred with symptomatic ventricular arrhythmias who had no family history, no genetic mutations associated with heart disease, and no other identified etiology after through clinical work-up. All patients in both groups were recommended to avoid high intensity exercise. Progression of the structural phenotype was assessed by regular repeated echocardiographic examinations during long-term follow-up. Right ventricular (RV) function and size were assessed by RV fractional area change (FAC), RV basal diameter (RVD) and RV outflow tract (RVOT) diameter. Disease progression was evaluated and compared using linear mixed model regression. RESULTS: Forty-one EiAC patients (15% women, age 45±13 years) and 84 AC probands (51% mutation positive, 35% women, age 43±15) were followed for 6.6 (IQR 3.7-10.5) and 7.9 (IQR 5.2-10.8) years, respectively. Key parameters from 570 echocardiographic examinations (184 EiAC and 386 AC) were assessed. There was no deterioration of RV function during follow-up in EiAC patients, in contrast to AC patients (FAC yearly progression rate: EiAC +0.02% [95% CI -0.27 to 0.31] vs AC -0.60% [95% CI -0.71 to -0.50] per year, p=0.001, Figure left panel). RV size did not increase in EiAC patients in contrast to AC patients (RVD: EiAC +0.01 mm [95% CI -0.00 to 0.03] vs AC +0.78 mm [95% CI 0.68 to 0.89] per year, p<0.001, Figure mid panel, and RVOT: EiAC +0.01 mm [95% CI -0.01 to 0.02] vs AC +0.47 mm [95% CI 0.38 to 0.56] per year, p<0.001, Figure right panel). CONCLUSION: Patients with exercise-induced AC had no evidence of disease progression during long-term follow-up. These patients had a more benign disease trajectory than patients with desmosomal AC. Despite the limited sample size, these results seem reassuring for patients diagnosed with exercise-induced AC. [Figure: see text]