Vigorous Exercise in Patients with Hypertrophic Cardiomyopathy: Results of the Prospective, Observational, Multinational, “Lifestyle and Exercise in HCM” (LIVE-HCM) Study

IMPORTANCE: Whether vigorous intensity exercise increases risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. OBJECTIVE: To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported non-vigorous activity. DESIGN: Investigator-initiated, prospective observational study. Participants were enrolled 5/2015 to 2/2019, median follow up of 38 months completed 2/2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous intensity exercise. SETTING: Multicenter, observational registry with recruitment at 42 high-volume HCM centers in the United States and internationally. Patients could also self-enroll through the central site. PARTICIPANTS: Individuals 8-60 years old diagnosed with HCM, or genotype-positive without left ventricular hypertrophy (phenotype-negative), without conditions precluding exercise, were enrolled. EXPOSURE: Amount and intensity of physical activity MAIN OUTCOMES AND MEASURES: The primary pre-specified composite endpoint included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate ICD shocks. All outcome events were adjudicated by an Events Committee blinded to the patient’s exercise category. RESULTS: Among the 1660 participants, 252 were classified as sedentary (15%), 709 (43%) participated in moderate, and 699 (42%) in vigorous intensity exercise (259 competitively, 37% of vigorous group). Seventy-seven individuals (4.6%) reached the composite endpoint: 44 (4.6%) of those classified non-vigorous, and 33 (4.7%) classified vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years. In multivariate Cox regression analysis of the primary composite endpoint, individuals engaging in vigorous exercise did not experience a higher rate of events compared to the non-vigorous group with adjusted hazard ratio (HR) of 1.01. The upper 95% one-sided confidence level (UCL) is 1.48, below the pre-specified boundary of 1.5 for non-inferiority. CONCLUSIONS AND RELEVANCE: Among individuals with HCM, or those who are genotype-positive/phenotype -negative, who are managed in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or the sedentary. These data will inform discussion between the patient and their expert care provider around exercise participation.