Exercise Training in Hypertrophic Cardiomyopathy: A Systematic Review, Meta-analysis, and Meta-regression

Abstract

BACKGROUND: A paradigm shift has emerged regarding exercise participation in patients with hypertrophic cardiomyopathy (HCM), with recent studies suggesting that structured training may improve functional capacity and cardiopulmonary responses. However, the effects of structured exercise interventions in HCM have not been comprehensively synthesized. AIM: The main objective was to determine the effect of exercise training on bodyweight, functional capacity, echocardiography, blood pressure, heart rate (HR), double product, and NT-proBNP in HCM patients. METHODS: Randomized controlled trials (RCTs) and non-randomized individualized endurance and concurrent training interventions including cardiopulmonary exercise test and echocardiographic measures in adult (? 18 years) obstructive and non-obstructive HCM patients were extracted from PubMed, Web of Science, and Cochrane in December 2025. Random-effects meta-analyses and meta-regressions were performed, and risk of bias was assessed using the ROBINS-I V2 tool for internal validity. RESULTS: Data from 8 studies (3 RCTs) with 205 low to moderate risk patients showed that training significantly (all p < 0.05) increased [mean (95% CI)]: peak VO(2) (pVO(2)) [2.3 (0.76, 3.83) mL kg(-1) min(-1)], predicted pVO(2) [8.1 (2.7, 13.4) %], exercise time [1.0 (0.5, 1.5) min], peak HR [5.2 (0.04, 10.3) bpm], and HR reserve (HRR) [5.5 (2.5, 8.5) bpm]; and decreased body mass index [- 1.12 (- 2.13, - 0.11) kg m(-2)], and rest HR [- 3.1 (- 5.7, - 0.4) bpm]. A lower baseline HRR was associated with broader increments in pVO(2) [1.3 (0.8, 1.9) mL kg(-1)·min(-1), R(2) = 0.86, p < 0.05, per 10-unit decrease]. A small between-group difference in maximal wall thickness was observed in controlled data compared to usual care [- 0.9 (- 1.7,- 0.1) mm, p < 0.05, k = 3]. Other echocardiographic features, blood pressure, and NT-proBNP did not change. There were no differences between endurance and concurrent training. No adverse events were reported in these cohorts. CONCLUSION: Individualized exercise interventions in low to moderate risk HCM patients were associated with improvements in functional capacity, exercise tolerance, cardiac adaptability, and chronotropic competence. The effect of beta-blockers on HRR and subsequent functional adaptations to training warrants future research. LIMITATIONS: Results should be interpreted cautiously due to heterogeneous study populations, predominantly mild/low-risk HCM phenotypes, the limited number of interventions, and restricted generalizability beyond individualized, guided, and mostly on-site supervised exercise settings. Trial registration The protocol was registered in PROSPERO: CRD420251058384. INFOGRAPHIC.