Improvement in peakV̇O₂ after 3-months of supervised exercise training in patients with heart failure with preserved ejection fraction: role of sex difference

Isabel Fegers-Wustrow (München)1, M. Haykowsky (Edmonton)2, E. B. Winzer (Dresden)3, A. B. Gevaert (Edegem)4, E. van Craenenbroeck (Edegem)4, R. Wachter (Leipzig)5, B. Pieske (Berlin)6, F. Edelmann (Berlin)7, M. Halle (München)1, S. Müller (München)1

1Klinikum rechts der Isar, Technische Universität München Präventive Sportmedizin und Sportkardiologie München, Deutschland; 2College of Health Sciences, University of Alberta Faculty of Nursing, Research Chair in Aging and Quality of Life Edmonton, Kanada; 3Herzzentrum Dresden GmbH an der TU Dresden Klinik für Innere Medizin, Kardiologie und Intensivmedizin Dresden, Deutschland; 4Antwerp University Hospital (UZA) Department of Cardiology Edegem, Belgien; 5Universitätsklinikum Leipzig Klinik und Poliklinik für Kardiologie Leipzig, Deutschland; 6Charité Universitätsmedizin Berlin Berlin, Deutschland; 7Charité - Universitätsmedizin Berlin Leiter des Clinical Study Center CVK Berlin, Deutschland


Background: Exercise training (ET) is an effective therapy to improve peakV̇O2 in patients with heart failure with preserved ejection fraction (HFpEF). However, uncertainty remains regarding sex differences in the change in peakVO2 in response to ET in HFpEF. 

Purpose: To evaluate the effects of a 3-month supervised ET on peakV̇O2 in female and male HFpEF patients.

Methods: We integrated the initial 3-month data from the two largest randomized controlled trials of exercise training in chronic HFpEF to date: OptimEx-Clin and Ex-DHF. Both trials compared the effects of 3-5 days/week of ET (high-intensity interval training or moderate-intensity continuous exercise with or without resistance training) versus usual care (UC) receiving general exercise advice. For the present analysis, all exercise training groups and both control groups were combined into one exercise (ET) and one control group (UC). PeakV̇O2 was defined as the highest 10-second average within the last minute of symptom-limited incremental cardiopulmonary exercise testing (CPET). Change in peak V̇O2 was analyzed separately for men and women (using independent t-tests) and compared between sexes by applying linear regression analysis with an interaction term between group and sex. All analyses were performed using R Statistical Software with significance levels of α = 0.05.

Results: Among the 502 randomized patients, 453 patients with available CPET data at three months were included in this analysis (ET: 159 women, 92 men; UC: 120 women, 82 men). At 3-month follow-up, there was a significant group by sex interaction for the change in peakV̇O2 (interaction P = 0.05). Women significantly increased peakV̇O2 after ET (1.1 ± 2.9 mL/kg/min) compared to a decrease of -0.6 ± 2.9 mL/kg/min following UC (mean difference:1.7 mL/kg/min ,95% CI, 1.0 to 2.3, P < 0.001). Men also increased peakV̇O2 in the ET group (1.1 ± 3.2 mL/kg/min); however, compared to UC (0.5 ± 3.0 mL/kg/min) the change was not significantly different (mean difference, 0.5 mL/kg/min [95% CI, -0.4 to 1.4], P = 0.27) (Figure 1). 

Conclusion: After three months of supervised ET, female HFpEF patients had a significantly greater improvement in relative peakV̇O2 compared to men. Effects in both ET groups were similar. However, in contrast to male HFpEF patients, peakV̇O2 deteriorated in female patients randomized to usual care. Therefore, the observed sex difference is caused by the ability to counteract the deconditioning effect which was only observed in female patients in the UC group. 



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