Factors associated with high-intensity physical activity and sudden cardiac death in hypertrophic cardiomyopathy

Background High-intensity physical activity has traditionally been discouraged in patients with hypertrophic cardiomyopathy due to concerns about triggering sudden cardiac death. However, current guidelines adopt a more liberal stance, and evidence on risk factors for exercise-related sudden cardiac death remains limited. This study investigated the clinical, morphological and genetic factors associated with high-intensity physical activity-related sudden cardiac death in hypertrophic cardiomyopathy. Methods This retrospective study included 75 patients with documented sudden cardiac death events from a cohort of 2619 patients with hypertrophic cardiomyopathy evaluated between 2005 and 2023. Physical activity levels at the time of the sudden cardiac death event were classified as high-intensity (≥6 metabolic equivalents) or low-intensity to moderate-intensity. Clinical and imaging characteristics, cardiopulmonary exercise test findings and genetic data were compared between the groups. Results Among the 75 patients, 15 (20%) experienced sudden cardiac death events during high-intensity activity. These patients were younger than those with events during low-intensity or moderate-intensity activity (median age: 25 (IQR 16–43) years vs 56 (48–64) years, p<0.001). High-intensity activity-related events were associated with higher European Society of Cardiology sudden cardiac death risk scores (median 4.9 vs 2.4, p=0.023) and fewer ventricular arrhythmias during exercise testing. However, there were no differences in the degree of left ventricular hypertrophy, left ventricular outflow tract obstruction, left ventricular systolic or diastolic function or genetic findings between groups. In multivariable analysis, younger age was the only independent risk factor of high-intensity activity-related sudden cardiac death events. Recurrent events in patients who survived initial high-intensity activity-related sudden cardiac death were triggered by subsequent high-intensity activity. Conclusions High-intensity physical activity-related sudden cardiac death in hypertrophic cardiomyopathy is associated with younger age; however, in this small cohort, no associations were found with traditional risk factors, including left ventricular hypertrophy or obstructive physiology.