Randomized Controlled Trial of Moderate- and High-Intensity Exercise Training in Patients With Hypertrophic Cardiomyopathy: Effects on Fitness and Cardiovascular Response to Exercise

Abstract

Background Moderate intensity exercise training (MIT) is safe and effective for patients with hypertrophic cardiomyopathy, yet the efficacy of high intensity training (HIT) remains unknown. This study aimed to compare the efficacy of HIT compared with MIT in patients with hypertrophic cardiomyopathy. Methods and Results Patients with hypertrophic cardiomyopathy were randomized to either 5 months of MIT, or 1 month of MIT followed by 4 months of progressive HIT. Peak oxygen uptake (V˙O₂; Douglas bags), cardiac output (acetylene rebreathing), and arteriovenous oxygen difference (Fick equation) were measured before and after training. Left ventricular outflow gradient and volumes were measured by echocardiography. Fifteen patients completed training (MIT, n=8, age 52±7 years; HIT, n=7, age 42±8 years). Both HIT and MIT improved peak V˙O₂ by 1.3 mL/kg per min (P=0.009). HIT (+1.5 mL/kg per min) had a slightly greater effect than MIT (+1.1 mL/kg per min) but with no statistical difference (group×exercise P=0.628). A greater augmentation of arteriovenous oxygen difference occurred with exercise (Δ1.6 mL/100 mL P=0.005). HIT increased left ventricular end-diastolic volume (+17 mL, group×exercise P=0.015) compared with MIT. No serious arrhythmias or adverse cardiac events occurred. Conclusions This randomized trial of exercise training in patients with hypertrophic cardiomyopathy demonstrated that both HIT and MIT improved fitness without clear superiority of either. Although the study was underpowered for safety outcomes, no serious adverse events occurred. Exercise training resulted in salutary peripheral and cardiac adaptations. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03335332.

Keywords: arrhythmias; cardiac output; exercise; fitness; high intensity; hypertrophic cardiomyopathy; training.

Figure 1. Overview of study design.

Schematic of study design (left) and Consolidated Standards of Reporting Trials diagram (right) showing flow of participants through the study. EF indicates ejection fraction; HCM, hypertrophic cardiomyopathy; HF, heart failure; HIT, high intensity training; LVOT, left ventricular outflow tract; MIT, moderate intensity training; and NYHA, New York Heart Association Class.

Figure 2. Primary change in fitness after exercise training.

Group response in peak V̇O₂ to exercise training, independent of intensity, is shown as absolute V̇O₂ (A) and indexed to body mass (C). B and D, The response in peak V̇O₂ to exercise training by intensity. Lines represent individual participant changes and bars mean value of the group. Exercise effect and group×exercise interaction of a repeated measures mixed model are shown. HIT indicates high intensity training; MIT, moderate intensity training; and V̇O₂, oxygen uptake.

Figure 3. Cardiac and peripheral responses to exercise.

Group changes in peak cardiac output (A), augmentation of cardiac output during peak exercise (B), peak arteriovenous oxygen difference, (C), and augmentation of arteriovenous oxygen difference during peak exercise (D) are shown, independent of exercise intensity. Exercise effect of repeat measures mixed model are shown.

Figure 4. Summary of study results.

Summary of study design and results are shown. HIT indicates high intensity training; ICD, implantable cardiac defibrillator; ILR, implantable loop recorder; LV, left ventricular; MIT, moderate intensity training; and VO₂, oxygen uptake.