Peak O2‐pulse predicts exercise training‐induced changes in peak V̇O2 in heart failure with preserved ejection fraction

Abstract

Aims

Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O₂) 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 V̇O₂ are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O₂‐pulse (V̇O₂ × HR⁻¹, reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O₂, is inversely associated with the change in peak V̇O₂ (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 V̇O₂ (%) was analysed as a function of baseline peak V̇O₂ and its determinants (absolute peak V̇O₂, peak O₂‐pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak V̇O₂ through changes in peak O₂‐pulse, peak HR and weight were analysed by a causal mediation analysis with multiple correlated mediators. Change in submaximal exercise tolerance (V̇O₂ 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 O₂‐pulse explained approximately 72% of the difference in changes in peak V̇O₂ 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 O₂‐pulse on change in peak V̇O₂ (interaction P = 0.04). In the ET group, every 1 mL/beat higher baseline peak O₂‐pulse was associated with a decreased mean change in peak V̇O₂ 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 V̇O₂ (P > 0.05). Change in V̇O₂ at VT1 was not associated with any of the investigated factors (P > 0.05).

Conclusions

In patients with HFpEF, the easily measurable peak O₂‐pulse seems to be a good indicator of the potential for improving peak V̇O₂ through exercise training. While changes in submaximal exercise tolerance were independent of baseline peak O₂‐pulse, patients with high O₂‐pulse may need to use additional therapies to significantly increase peak V̇O₂.