Long-term effects of exercise training in patients with heart failure with preserved ejection fraction - a follow-up study of two randomised controlled trials
Authors: Fegers-Wustrow I , Maderthaner S , Haykowsky M , Treitschke J , Gevaert A , Winzer E , Edelmann F , Wachter R , Adams V , Van Craenenbroeck E , Pieske B , Halle M , Mueller S 
Published: June 2024

Abstract

Background
Exercise training (ET) is an effective therapy to improve peak oxygen consumption (V̇O2) in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unknown if such an intervention has a sustainable effect beyond the active study period.

Purpose
To investigate peakV̇O2 in the long-term period after completing a one-year ET intervention in HFpEF.

Methods
This is a long-term follow-up (FU) study of patients enrolled in the OptimEx-Clin or Ex-DHF trial, the two largest randomised controlled trials of ET over one year in HFpEF. In the OptimEx-Clin trial, 180 patients (mean age: 70 years; 67% women) with HFpEF were randomised to high-intensity interval training, moderate continuous training or usual care (UC). In the Ex-DHF trial, 322 patients (mean age: 70 years; 60% women) were randomised to endurance plus resistance training or UC. All patients who were randomised in one centre and completed the respective trial were contacted to participate in this FU. Baseline assessments were conducted between May 2013 and April 2017 with the last active study visit in May 2018. Patients were reassessed for FU between December 2021 and August 2022. Primary endpoint was the absolute change in peakV̇O2 between the baseline and FU visit. All exercise and both control groups were combined into one ET and one UC group. PeakV̇O2 was assessed during symptom-limited cardiopulmonary exercise testing (CPET) on a cycle ergometer at baseline, 3, 6, 12 months and at FU. PeakV̇O2 was defined as the highest 30-second average within the last minute of CPET. Statistical analyses were performed using dependent and independent t-tests with α = 0.05.

Results
Among 142 initially randomised patients, 75 were recruited for FU and 67 (40 ET; 27 UC) had available CPET data both at baseline and FU (75% women; mean [SD] age at baseline: 66±7 years). Mean time between baseline and FU was 6.3 ± 1.3 and 6.6 ± 0.8 years in the ET and UC groups, respectively. During the active study phase, ET patients significantly increased peakV̇O2 from baseline to 3, 6 and 12 months (mean change [95% CI]: 1.5 [0.6 to 2.3], 1.5: [0.5 to 2.4] and 1.4: [0.3 to 2.5] mL/kg/min, respectively; Fig. 1). However, a statistically significant difference between groups was only observed at 3 months (P=0.03). The change in peakV̇O2 from baseline to FU was not significantly different between both groups (ET: -2.7 ± 3.3 mL/kg/min; UC: -2.5 ± 3.6 mL/kg/min; P=0.87) (Fig. 1). Finally, between 12 months and FU, change in peakV̇O2 was -4.2 ± 3.6 mL/kg/min for ET, and -3.4 ± 3.3 mL/kg/min for UC patients (P=0.35).

Conclusions
While patients with HFpEF had significantly improved peakV̇O2 between 3 and 12 months of ET (~1.5 mL/kg/min), these effects were not sustainable beyond the active study period. This finding highlights the importance of incorporating behavioural strategies to ensure long-term adherence to ET is maintained for optimal benefits in peakV̇O2 over time. Change in peakV̇O2 (mean and 95% CI)