Exercise Training in Patients With Hypertrophic Cardiomyopathy Without Left Ventricular Outflow Tract Obstruction: A Randomized Clinical Trial

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Abstract
BACKGROUND: Patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction commonly experience reduced exercise capacity. Physical training improves exercise capacity in these patients, but whether the underlying effects of exercise are a result of central hemodynamic or peripheral improvement is unclear. This study assessed whether exercise training reduces left ventricular filling pressure measured during exercise in patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction. METHODS: Between March 2019 and June 2022, patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction were randomly assigned (1:1) to a 12-week (3 h/wk) supervised, moderate-intensity exercise training program or continued usual activity. The primary outcome was the change in invasively measured pulmonary capillary wedge pressure during mild exercise (25 W) from baseline to week 12. Pressure tracings were analyzed offline by a blinded investigator. Secondary outcomes included changes in peak oxygen consumption, cardiac index, quality of life, echocardiographic indices of diastolic function, and natriuretic peptides. RESULTS: Of 59 patients randomized (mean age, 58.1 [12.2] years; 27% women), 51 (86%) completed all follow-up assessments. At week 12, the change in 25-W pulmonary capillary wedge pressure was –2.8 (6.8) mm Hg in the exercise group, compared with +1.2 (4.9) mm Hg in the usual-activity group (between-group difference, 4.0 mm Hg [95% CI, 0.7–7.3]; P =0.018). Peak oxygen consumption improved by +1.8 (2.0) mL·kg⁻¹·min⁻¹ in the exercise group versus –0.3 (3.1) mL·kg⁻¹·min⁻¹ in the usual-activity group ( P =0.005). Exercise training improved the ventilatory efficiency (V E /VCO 2 ) slope compared with usual activity (between-group difference, 2.0 [95% CI, 0.6–3.5]; P =0.006). Peak cardiac index improved by +0.38 (1.38) L·min⁻¹·m⁻² in exercise versus –0.85 (1.20) L·min⁻¹·m⁻² in the usual-activity group ( P =0.002). Change in overall Kansas City Cardiomyopathy Questionnaire score was similar between groups. However, the change in physical limitation scores (+8.4 [12.0] points in exercise versus +0.7 [6.8] points in usual-activity group; P =0.034) and quality-of-life scores (+8.7 [18.0] points in exercise versus 0.7 [4.0] points in usual-activity group; P =0.01) differed significantly. There were no significant changes in diastolic function assessed by echocardiography or in natriuretic peptides. CONCLUSIONS: In patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction, a 12-week moderate-intensity exercise training program resulted in reduced left ventricular filling pressures at mild exertion and improved exercise performance. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03537183.

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