High-intensity exercise-related sudden cardiac death in hypertrophy cardiomyopathy

Abstract Background Whether exercise provokes sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is uncertain. Current European guidelines recommend against high-intensity exercise in individuals with high SCD risk or obstructive physiology. Purpose We investigated the factors associated with exercise-related SCD in HCM. Methods We retrospectively analyzed of 2,844 consecutive patients with HCM who underwent evaluation between 2005 and 2023 at a high-volume tertiary center. SCD events were defined as a composite of aborted SCD, appropriate implantable cardioverter-defibrillator (ICD) shock, and SCD. Among 80 first SCD events (2.8%), 75 events had a description of the physical activity at the time of the event. Patients were classified into two groups according to physical activity level at the time of the SCD event. Group 1 included patients with high-intensity exercise-related SCD events, defined as happening during or immediately after high-intensity exercise or physical activity, while Group 2 included patients with SCD events happening at rest or during light or moderate physical activity. Results The 75 first SCD events included 44 aborted SCD, 22 appropriate ICD shocks, and 9 SCD. Median age at SCD event was 54 (IQR 39.5–62.5) years and 60 (80%) were men. Patients in Group 1 (n=14) were younger than patients in Group 2 (n=61) (23.5 [IQR 16–48] vs. 55 [IQR 44–64] years, p<0.001), and most patients in group 1 (92.9%) were under the age of 60 years. Patients in Group 1 had slightly smaller left ventricular (LV) end-diastolic dimension and had higher ESC SCD risk scores (3.6 [IQR 2.5–6.7] vs. 2.4 [IQR 1.7–4.8], p=0.044) than patients in Group 2; however, there were no significant differences in the proportion of high-risk patients (28.6% vs. 14.8%, p=0.396) or patients with AHA major SCD risk factors (57.1% vs. 55.7%, p=0.999). Otherwise, there were no significant differences in the presence of obstructive physiology, apical HCM, and apical aneurysm, LV systolic and diastolic function, and comorbidities between the two groups. Furthermore, of the 29 patients who underwent genetic testing, there was no difference in the proportion of patients with pathogenic sarcomeric variants according to exercise-related SCD (50.0% vs. 65.2%, p=0.683). To note, there was a non-significant tendency towards higher proportion of thin filament variants in Group 1 than Group 2 among those with pathogenic sarcomeric variants (100% [3/3] vs 26.7% [4/15], p=0.084). Conclusions Most high-intensity exercise-related SCD events happened under the age of 60. The ESC SCD risk score was higher in patients with high-intensity exercise-related SCD events, although the SCD risk categories or AHA risk factors could not discriminate patients at higher risk of events. These results suggest that exercise recommendations should not be based on SCD risk category, presence of obstruction, or degree of LV hypertrophy.