Effect of exercise training in patients with chronotropic incompetence and heart failure with preserved ejection fraction: Training-HR study protocol

Chronotropic incompetence (ChI) is linked with diminished exercise capacity in heart failure with preserved ejection fraction (HFpEF). Although exercise training has shown potential for improving functional capacity, the exercise modality associated with greater functional and chronotropic response (ChR) is not well-known. Additionally, how the ChR from different exercise modalities mediates functional improvement remains to be determined. This study aimed to evaluate the effect of three different exercise programs over current guideline recommendations on peak oxygen consumption (peakVO2) in patients with ChI HFpEF phenotype. In this randomized clinical trial, 80 stable symptomatic patients with HFpEF and ChI (NYHA class II-III/IV) are randomized (1:1:1:1) to receive: a) a 12-week program of supervised aerobic training (AT), b) AT and low to moderate-intensity strength training, c)AT and moderate to high-intensity strength training, or d) guideline-based physical activity and exercise recommendations. The primary endpoint is 12-week changes in peakVO2. The secondary endpoints are 12-week changes in ChR, 12-week changes in quality of life, and how ChR changes mediate changes in peakVO2. A mixed-effects model for repeated measures will be used to compare endpoint changes. The mean age is 75.1 ± 7.2 years, and most patients are women (57.5 %) in New York Heart Association functional class II (68.7 %). The mean peakVO2, percent of predicted peakVO2, and ChR are 11.8 ± 2.6 mL/kg/min, 67.2 ± 14.7 %, and 0.39 ± 0.16, respectively. No significant baseline clinical differences between arms are found. Training-HR will evaluate the effects of different exercise-based therapies on peakVO2, ChR, and quality of life in patients with ChI HFpEF phenotype. ClinicalTrials.gov (NCT05649787).