Sympathetic Neural Responses To Exercise Training In Heart Failure With Preserved Ejection Fraction

Patients with heart failure with preserved ejection fraction (HFpEF) exhibit elevated basal sympathetic drive, which may be associated with their exercise intolerance and poor clinical outcomes. Exercise training has been shown to be effective in reducing sympathetic neural activity in patients with heart failure with reduced ejection fraction. However, whether this is also true in HFpEF remains unknown. PURPOSE: We determined 1) whether exercise training would reduce basal sympathetic neural activity in patients with HFpEF, and 2) whether different exercise modes (i.e., whole-body vs. single-leg exercise) would affect sympathetic activity differently. METHODS: Forty-one patients with HFpEF were randomized to either whole-body dynamic exercise using cycling (4 days/week, 30 min/session; n = 22, 14 women, 70 ± 6 [SD] yrs) or single-leg knee extension (4 days/week, 10 min/leg; n = 19, 14 women, 69 ± 8 yrs) for 16 weeks. Before and after exercise training, peak oxygen uptake (V̇O2) was assessed during graded maximal cycle exercise. In addition, systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), and muscle sympathetic nerve activity (MSNA, microneurography) were measured during 10 minutes of supine rest. RESULTS: Peak V̇O2 was improved following whole-body exercise training (P < 0.001), but not single-leg knee extension training (P = 0.851). In contrast, resting MSNA remained unchanged after whole-body exercise training (pre: 35 ± 14 vs. post: 34 ± 12 bursts/min) and single-leg knee extension training (41 ± 13 vs. 38 ± 21 bursts/min, Pinteraction = 0.879). Further, there were no significant differences in resting SBP, DBP and HR between pre- and post-training, regardless of the exercise mode (all P > 0.05). CONCLUSIONS: Whole-body exercise training, but not single-leg knee extension for 16 weeks improved exercise capacity in patients with HFpEF. However, sympathetic neural activity at rest did not change after both modes of exercise training in these patients. Future research is warranted to seek other therapeutic options to attenuate sympathetic overactivity and improve clinical outcomes in HFpEF. Supported by: Supported by the National Institutes of Health (P01HL137630), Harry S Moss Heart Trust, Bank of America, N.A., Trustee and the American Heart Association postdoctoral fellowship award (24POST1191431).