Exercise training in hypertrophic cardiomyopathy: a meta-analysis of randomised trials with trial sequential analysis

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death (SCD) among young individuals and athletes. Despite increasing evidence supporting exercise, uncertainty remains about its safety and efficacy in this population. METHODS: We systematically reviewed randomised controlled trials (RCTs) comparing structured exercise interventions with usual care in patients with HCM. The primary outcome was peak oxygen consumption (pVO₂). Random-effects meta-analysis and trial sequential analysis (TSA) were applied to assess efficacy and robustness of evidence. RESULTS: Four RCTs (n=290) were included, enrolling predominantly low-risk, non-obstructive HCM patients with mild functional limitation (mean left ventricular ejection fraction (LVEF) 66%). Exercise improved pVO₂ (mean difference (MD) 1.81 mL/kg/min; 95% CI 1.01 to 2.61; p<0.01), confirmed by TSA. Exercise also reduced left ventricular wall thickness (MD -0.56 mm; 95% CI -0.97 to -0.16) and body mass index (MD -0.65 kg/m²; 95% CI -1.05 to -0.25) without significant changes in LVEF or left ventricular outflow gradients. No increase was observed in arrhythmias, syncope, SCD or other adverse events. However, the total number of RCTs and participants was small, and all studies primarily involved mild, non-obstructive phenotypes, limiting generalisability. CONCLUSIONS: In patients with mild, non-obstructive HCM, structured exercise appears safe and improves functional capacity and cardiometabolic parameters without adverse ventricular effects. Larger multicentre RCTs including higher-risk phenotypes are warranted to confirm safety and define optimal training strategies. PROSPERO REGISTRATION NUMBER: CRD420251012232.