Response to Exercise Training and Outcomes in Patients With Heart Failure and Diabetes Mellitus: Insights From the HF-ACTION Trial

• DM was associated with lower adherence to exercise and reduced peak VO2 and 6MWD at baseline.
• DM patients have an attenuated response to exercise, independent of reduced adherence.
• DM patients have cardiac and peripheral dysfunction that result in attenuated exercise tolerance.
• DM was associated with increased hospitalization, driven by non-HF hospitalizations.

BackgroundIn HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), exercise training improved functional capacity in heart failure with reduced ejection fraction (HFrEF). Previous studies have suggested that diabetes mellitus (DM) may be associated with an attenuated response to exercise. We explored whether DM attenuated the improvement in functional capacity with exercise.Methods and ResultsHF-ACTION randomized 2331 patients with HFrEF to medical therapy with or without exercise training over a median follow-up of 2.5 years. We examined the interaction between DM and exercise response measured by change in 6-minute walk distance (6MWD) and peak VO2. We also examined outcomes by DM status. In HF-ACTION, 748 (32%) patients had DM. DM patients had lower functional capacity at baseline and had lower exercise volumes at 3 months. There was a significant interaction between DM status and exercise training for change in peak VO2 (interaction P = .02), but not 6MWD. In the exercise arm, DM patients had a smaller mean increase in peak VO2 than non-DM patients (P = .03). There was no interaction between DM and exercise on clinical outcomes. After risk adjustment, DM was associated with increased all-cause mortality/hospitalization (P = .03).ConclusionsIn HF-ACTION, DM was associated with lower baseline functional capacity, an attenuated improvement in peak VO2, and increased hospitalizations.