Peak O -pulse predicts exercise training-induced changes in peak V̇O in heart failure with preserved ejection fraction.

AIMS

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

CONCLUSIONS

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