High-intensity exercise program appears to be feasible, effective, and safe in HCM

In a feasibility RCT among patients with hypertrophic cardiomyopathy (HCM), 85% completed a 12-week exercise program, with potentially improved cardiorespiratory fitness, reduced CVD risk factors, psychological benefits, and no increase in arrhythmias compared with usual care.

This summary is based on the publication of Basu J, Nikoletou D, Miles C, et al. - High intensity exercise programme in patients with hypertrophic cardiomyopathy: a randomized trial. Eur Heart J. 2025 May 14;46(19):1803-1815. doi: 10.1093/eurheartj/ehae919.

Introduction and methods

Background

Until recently, hypertrophic cardiomyopathy (HCM) was considered as a predominant cause of sudden cardiac death (SCD) in young athletes [1]. However, contemporary studies have suggested that the exercise-related risk of adverse events including SCD in patients with HCM may not be as high as initially thought [2-8], and current clinical guidelines support a more liberal approach towards exercise in this population [9,10]. Still, data on feasibility, safety, and outcomes from large-scale RCTs are lacking.

Aim of the study

The authors examined the feasibility of a high-intensity exercise program in young and middle-aged HCM patients and explored the safety and efficacy of this program with regard to cardiorespiratory fitness, CVD risk factors, and psychological parameters, and quality of life (QoL).

Methods

In a feasibility RCT (previously known as the SAFE-HCM trial) conducted at 3 tertiary centers in London, the UK, 80 HCM patients aged 16–60 years were block randomized to a supervised, individually tailored, high-intensity (85% of maximum heart rate reserve) exercise program in addition to usual care or usual care only for 12 weeks. Inclusion criteria included NYHA class I–II HF symptoms and ability to participate in high-intensity exercise. Competitive athletes were excluded.

All participants underwent assessments, including physical examination, routine laboratory tests, 12-lead ECG, and transthoracic echocardiography, at baseline and 12 weeks. The exercise group was reevaluated 6 months after completion of the program.

Outcomes

Feasibility of the exercise program was assessed by: (1) recruitment rate (including reasons for refusal), (2) adherence rate, (3) staffing and resource assessments, and (4) acceptability of the intervention and associated educational materials.

The exploratory primary safety endpoint was a composite outcome of CV death, cardiac arrest, appropriate or inappropriate ICD therapy, exercise-induced syncope, sustained ventricular tachycardia (VT), nonsustained VT, or sustained atrial arrhythmias (≥30 s).

Exploratory secondary endpoints included changes in: (a) cardiorespiratory fitness, (b) CVD risk factors, and (c) scores for QoL (assessed with World Health Organization Disability Assessment Schedule II and 36-Item Short Form Survey), anxiety, and depression (latter 2 assessed with Hospital Anxiety and Depression Scale).

Main results

Feasibility

• Initially, 205 eligible patients were invited, of whom 80 agreed to participate (39.0%). Commonly cited reasons for refusal were travel distance (n=85) and work (n=16) or family (n=6) commitments.
• Of the randomized patients, 34 participants (85.0%) randomized to the exercise program and 33 (82.5%) assigned to usual care completed the 12-week follow-up.
• Resources including staffing and equipment were in accordance with national cardiac rehabilitation standards.

Safety and efficacy at 12 weeks

• There was no difference in the exploratory primary safety endpoint (i.e., composite outcome of arrhythmia-related events) at 12 weeks between the exercise and usual-care groups (P=0.99). One participant in the exercise group experienced exercise-induced syncope after developing ventricular standstill during exertion, and 1 participant in the usual-care group had an episode of sustained VT. Both individuals had no further complications.
• At 12 weeks, the exercise group showed greater mean ± SD increases in peak oxygen consumption (VO₂) (1.9 ± 2.9 vs. –2.1 ± 8.1 mL/kg/min; difference: 4.1 mL/kg/min; 95%CI: 1.1–7.1) and VO₂ at anaerobic threshold (2.0 ± 3.9 vs. −0.3 ± 3.6 mL/kg/min; difference: 2.3 mL/kg/min; 95%CI: 0.4–4.1) than the usual-care group.
• The exercise group also demonstrated larger mean ± SD decreases in systolic blood pressure (−10.3 ± 8.9 vs. −2.6 ± 9.9 mmHg; difference: –7.3 mmHg; 95%CI: –11.7 to –2.8) and BMI (−0.7 ± 0.8 vs. 0.1 ± 0.7 kg/m²; difference: –0.8 kg/m²; 95%CI: –1.1 to –0.4), compared with the usual-care group.
• In addition, greater mean ± SD reductions in scores for anxiety (−2.7 ± 3.2 vs. 0.3 ± 2.1; difference: –3; 95%CI: –4.3 to –1.7) and depression (−1.8 ± 2.8 vs. −0.1 ± 1.8; difference: –1.7; 95%CI: –2.9 to –0.5) were observed in the exercise versus usual-care group.
• There were no significant between-group differences in QoL, levels of cholesterol, HbA1c, and cardiac biomarker, or echocardiographic parameters.

Exercise group evaluation at 6 months

• At 6 months, self-reported physical activity levels appeared to have returned to baseline levels among participants in the exercise group who returned for the repeat evaluation (n=33).
• In line with this, most improvements seemed to have dissipated.
• No arrhythmic events or increased prevalence of nonsustained VT were recorded.

Conclusion

This multicenter feasibility RCT among UK patients with HCM showed a 12-week, supervised, high-intensity exercise program was feasible (completion rate: 85%) and suggested it led to improved cardiorespiratory fitness, reduced CVD risk factors, and psychological benefits compared with usual care, with no increase in arrhythmias. The authors acknowledge a “large-scale study, in cohorts with greater heterogeneity, is required to corroborate findings and assess long-term safety of high-intensity exercise in HCM.”

Find this article online at Eur Heart J.

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