Combined endurance and resistance exercise training in heart failure with preserved ejection fraction: a randomized...

Endurance exercise training (ET) is an effective treatment in heart failure with preserved ejection fraction (HFpEF), but the efficacy of resistance training in this patient population has been only scarcely evaluated. In this multicenter, randomized trial, we evaluated the effects of combined endurance and resistance training over 12 months in patients with HFpEF. The primary endpoint was a modified Packer score, including all-cause mortality, hospitalizations classified as potentially related to heart failure or exercise and changes in peak oxygen consumption ( $\dot{V}{O}_2$ ), diastolic function (E/e'), New York Heart Association (NYHA) class and global self-assessment (GSA). In total, 322 patients (mean age, 70 years; 192 females (59.6%) and 130 males (40.4%)) were randomized (1:1) to ET or usual care (UC). At 12 months, the modified Packer score showed an improvement in 33 ET patients (20.5%) and in 13 UC patients (8.1%) and showed a worsening in 69 ET patients (42.9%) and in 71 UC patients (44.1%) (Kendall's tau-b = -0.073, P = 0.17). Although the primary endpoint was not met, clinically relevant differences favoring the ET group as compared to the UC group were observed for the following secondary endpoints: changes in peak $\dot{V}{O}_2$ (mean difference, 1.3 ml kg^-1 min^-1 (95% confidence interval (CI): 0.4-2.1)) and NYHA class (odds ratio = 7.77 (95% CI: 3.73-16.21)). No significant between-group differences were observed for other secondary endpoints, including change in E/e', change in GSA, time to cardiovascular hospitalization or all-cause mortality. In conclusion, 1 year of combined endurance and resistance ET did not result in a significantly better modified Packer score, but it did result in improvements in important clinical parameters, such as peak $\dot{V}{O}_2$ and NYHA class, as compared to UC. ISRCTN registration: ISRCTN86879094 .