Peak O2-pulse predicts exercise training-induced changes in peak VO2 in heart failure with preserved ejection fraction

Aims Exercise training (ET) has been consistently shown to increase peak oxygen consumption (VO2) 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 VO2 are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O-2-pulse (VO2 x HR-1, reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak VO2, is inversely associated with the change in peak VO2 (adjusted by body weight) following Er 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 VO2 (%) was analysed as a function of baseline peak VO2 and its determinants (absolute peak VO2, peak O-2-pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak VO2 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 (VO2 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 VO2 between Er 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 VO2 (interaction P = 0.04). In the Er group, every 1 mL/beat higher baseline peak O-2-pulse was associated with a decreased mean change in peak VO2 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 VO2 (P > 0.05). Change in VO2 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 VO2 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 VO2.