Peak O(2)‐pulse predicts exercise training‐induced changes in peak V̇O(2) in heart failure with preserved ejection fraction

ABSTRACT: AIMS: Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O(2)) in patients with heart failure with preserved ejection fraction (HFpEF); however, inter‐individual responses vary significantly. Because it is unlikely that ET‐induced improvements in peak V̇O(2) are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O(2)‐pulse (V̇O(2) × HR(−1), reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O(2), is inversely associated with the change in peak V̇O(2) (adjusted by body weight) following ET versus guideline control (CON) in patients with HFpEF. METHODS AND RESULTS: This was a secondary analysis of the OptimEx‐Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure, NCT02078947) trial, including all 158 patients with complete baseline and 3 month cardiopulmonary exercise testing measurements (106 ET, 52 CON). Change in peak V̇O(2) (%) was analysed as a function of baseline peak V̇O(2) and its determinants (absolute peak V̇O(2), peak O(2)‐pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak V̇O(2) through changes in peak O(2)‐pulse, peak HR and weight were analysed by a causal mediation analysis with multiple correlated mediators. Change in submaximal exercise tolerance (V̇O(2) at the ventilatory threshold, VT1) was analysed as a secondary endpoint. Among 158 patients with HFpEF (66% female; mean age, 70 ± 8 years), changes in peak O(2)‐pulse explained approximately 72% of the difference in changes in peak V̇O(2) between ET and CON [10.0% (95% CI, 4.1 to 15.9), P = 0.001]. There was a significant interaction between the groups for the influence of baseline peak O(2)‐pulse on change in peak V̇O(2) (interaction P = 0.04). In the ET group, every 1 mL/beat higher baseline peak O(2)‐pulse was associated with a decreased mean change in peak V̇O(2) of −1.45% (95% CI, −2.30 to −0.60, P = 0.001) compared with a mean change of −0.08% (95% CI, −1.11 to 0.96, P = 0.88) following CON. None of the other factors showed significant interactions with study groups for the change in peak V̇O(2) (P > 0.05). Change in V̇O(2) at VT1 was not associated with any of the investigated factors (P > 0.05). CONCLUSIONS: In patients with HFpEF, the easily measurable peak O(2)‐pulse seems to be a good indicator of the potential for improving peak V̇O(2) through exercise training. While changes in submaximal exercise tolerance were independent of baseline peak O(2)‐pulse, patients with high O(2)‐pulse may need to use additional therapies to significantly increase peak V̇O(2).