Endurance exercise is effective in improving peak oxygen consumption (peak V̇o2) in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unknown whether differing ...modes of exercise have different effects.
To determine whether high-intensity interval training, moderate continuous training, and guideline-based advice on physical activity have different effects on change in peak V̇o2 in patients with HFpEF.
Randomized clinical trial at 5 sites (Berlin, Leipzig, and Munich, Germany; Antwerp, Belgium; and Trondheim, Norway) from July 2014 to September 2018. From 532 screened patients, 180 sedentary patients with chronic, stable HFpEF were enrolled. Outcomes were analyzed by core laboratories blinded to treatment groups; however, the patients and staff conducting the evaluations were not blinded.
Patients were randomly assigned (1:1:1; n = 60 per group) to high-intensity interval training (3 × 38 minutes/week), moderate continuous training (5 × 40 minutes/week), or guideline control (1-time advice on physical activity according to guidelines) for 12 months (3 months in clinic followed by 9 months telemedically supervised home-based exercise).
Primary end point was change in peak V̇o2 after 3 months, with the minimal clinically important difference set at 2.5 mL/kg/min. Secondary end points included changes in metrics of cardiorespiratory fitness, diastolic function, and natriuretic peptides after 3 and 12 months.
Among 180 patients who were randomized (mean age, 70 years; 120 women 67%), 166 (92%) and 154 (86%) completed evaluation at 3 and 12 months, respectively. Change in peak V̇o2 over 3 months for high-intensity interval training vs guideline control was 1.1 vs -0.6 mL/kg/min (difference, 1.5 95% CI, 0.4 to 2.7); for moderate continuous training vs guideline control, 1.6 vs -0.6 mL/kg/min (difference, 2.0 95% CI, 0.9 to 3.1); and for high-intensity interval training vs moderate continuous training, 1.1 vs 1.6 mL/kg/min (difference, -0.4 95% CI, -1.4 to 0.6). No comparisons were statistically significant after 12 months. There were no significant changes in diastolic function or natriuretic peptides. Acute coronary syndrome was recorded in 4 high-intensity interval training patients (7%), 3 moderate continuous training patients (5%), and 5 guideline control patients (8%).
Among patients with HFpEF, there was no statistically significant difference in change in peak V̇o2 at 3 months between those assigned to high-intensity interval vs moderate continuous training, and neither group met the prespecified minimal clinically important difference compared with the guideline control. These findings do not support either high-intensity interval training or moderate continuous training compared with guideline-based physical activity for patients with HFpEF.
ClinicalTrials.gov Identifier: NCT02078947.
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.
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.
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).
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
.
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