Sex Differences in Exercise Training Response Among HFpEF Patients: Pooled Analysis of OptimEx-Clin and Ex-DHF-Trials

Exercise training improves exercise tolerance (peak oxygen consumption, peakV̇O2) in patients with heart failure with preserved ejection fraction (HFpEF), but it remains unclear whether the effects are comparable between sexes.

To evaluate sex-specific exercise training effects on peakV̇O2 in HFpEF.

This pooled analysis integrates data from patients with chronic HFpEF randomised to different modes of exercise training or usual care in the OptimEx-Clin and Ex-DHF-trials. Sex differences in changes of peakV̇O2 (absolute, relative, percent-predicted) from baseline to three, six, and 12 months of exercise training or usual care were compared using linear-mixed-models.

Among 498 patients (mean age 69.3 ± 7.7 years, 62% women), 277 (57%) were randomised to exercise training. Exercise training significantly increased absolute, relative and percent-predicted peakV̇O2 compared to usual care in women (all P < 0.001), but not in men (all P > 0.05). A significant sex difference in the training response was observed for percent-predicted peakV̇O2 (sex*group*time-interaction P = 0.037). Although mean within-group changes in percent-predicted peakV̇O2 following exercise training were similar between women and men (4.7% [95% CI, 2.2 to 7.2%] vs. 3.0% [-0.3 to 6.4%] at 12 months), usual care was associated with a decline in women (-3.7% [-6.5 to -0.8%]) but not in men (1.4% [-2.0 to 4.7%]).

Exercise training improved percent-predicted peakV̇O2 in women but not in men with HFpEF, a sex difference that was largely driven by differing responses following usual care. Since women are usually underrepresented in exercise programmes, more efforts should be made to increase their participation rates. (OptimEx-Clin: NCT02078947; ExDHF: ISRCTN86879094).