P3681Apparent sex differences in risk of life-threatening events in arrhythmogenic cardiomyopathy are related to exercise habits

Abstract

Abstract Background Arrhythmogenic cardiomyopathy (AC) is an inheritable heart disease characterized by high risk of ventricular arrhythmias and exercise intolerance. Male sex is associated with higher risk of life-threatening events. However, this may be challenged by the fact that men exercise more than women. Purpose To assess whether the sex differences in arrhythmic outcome in AC-patients are driven by sex differences in exercise exposure. Methods We included AC-patients diagnosed between 1997 and 2017 in a longitudinal cohort study. We assessed exercise habits during the preceding 3 years before inclusion, and exercise dose was expressed as metabolic equivalent hours per week (MET-hours/week). Life-threatening events were defined as sustained ventricular tachycardia, aborted cardiac arrest or appropriate therapy from an implantable cardioverter-defibrillator at the time of diagnosis and prospectively during follow-up. Results We included 170 AC-patients (52% probands, 44% female, age 41±16 years). Males had higher exercise doses than female patients (36 [IQR, 14 to 54] vs. 12 [IQR, 8 to 22] MET-hours/week; P<0.001). Fifty-seven patients (34%) had previous life-threatening events, and 45 (26%) had life-threatening events during 5.7 (IQR, 2.8 to 9.4) years of follow-up. Male sex seemed to be a marker of previous life-threatening events (OR 2.0 [95% CI, 1.0 to 3.8]; P<0.05), but not when adjusted for exercise dose (Adjusted OR 1.3 [95% CI, 0.6 to 2.7]; P=0.44). Male sex also seemed to be a predictor of life-threatening events during follow-up (HR 2.0 [95% CI 1.0 to 3.9]; P=0.04) (Figure, left panel), but not when adjusted for exercise dose (Adjusted HR 1.5 [95% CI 0.8 to 3.0]; P=0.26) (Figure, right panel). Conclusions Sex differences in arrhythmic risk in AC were attributable to higher exercise doses in male AC-patients. This highlights the importance of exercise assessment in these patients, and challenges the current opinion of male sex as a risk factor in itself. Risk stratification based on sex may underestimate the risk of physically active female AC-patients. Acknowledgement/Funding This study was supported by Center for Cardiological Innovation funded by the Norwegian Research Council