Effect of exercise training in patients with chronotropic incompetence and heart failure with preserved ejection fraction: the TRAINING-HR randomized clinical trial

Aims Chronotropic incompetence (ChI) in heart failure with preserved ejection fraction (HFpEF) is associated with a reduced exercise capacity. The role of exercise training in improving chronotropic response (ChR) and functional capacity in these patients remains uncertain. This study assessed the effects of four different exercise programmes on peak oxygen consumption (peakVO), Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and ChR in patients with the ChI HFpEF phenotype. Methods and results In this randomized clinical trial, 80 symptomatic (NYHA classes II-III/IV) patients with the ChI HFpEF phenotype were randomized (1:1:1:1) to one of four interventions: (i) a 12-week supervised aerobic training (AT) programme, (ii) AT with low-intensity strength training (AT/LRT), (iii) AT with moderate- to high-intensity strength training (AT/HRT), or (iv) non-supervised exercise recommendations (ER). The primary endpoint was the change in peakVO₂ at 12 weeks. Secondary endpoints included changes in ChR and KCCQ. A linear regression model was used. The mean age of 80 participants was 75.1 ± 7.2 years, and 59.6% were women. Baseline values for peakVO₂, chronotropic index, and KCCQ were 11.8 ± 2.6 mL/kg/min, 0.4 ± 0.2, and 63.5 ± 17.9, respectively, with no significant differences across arms. All supervised training programmes led to significant improvements in peakVO₂ compared to ER: AT/HRT: Δ + 4.0 [95% confidence interval (CI): 2.9-5.1, P < 0.001], AT/LRT: Δ + 3.6 (95% CI: 2.5-4.6, P < 0.001), and AT: Δ + 2.9 (95% CI: 1.9-4.0, P < 0.001). AT/HRT was superior over AT alone: Δ + 1.1 (95% CI, 0.1-2.2, P = 0.046). Likewise, supervised exercise improved ChR and KCCQ without statistical differences between groups. Conclusion Different supervised exercise training improved peakVO₂, ChR, and KCCQ in patients with ChI HFpEF phenotype.