AIMS: We tested the hypothesis that the effects of combined inspiratory muscle training and aerobic exercise training (IMT+AET) on muscle sympathetic nerve activity (MSNA) and forearm blood flow in patients with heart failure with reduced ejection fraction are more pronounced than the effects of AET alone. METHODS AND RESULTS: Patients aged 30 to 70 years, New York Heart Association Functional Class II to III, and left ventricular ejection fraction <= 40% were randomly assigned to four groups: IMT (n = 11), AET (n = 12), IMT+AET (n = 9), and non-training (NT; n = 10). MSNA was recorded using microneurography. Forearm blood flow was measured by venous occlusion plethysmography and inspiratory muscle strength by maximal inspiratory pressure. IMT consisted of 30 min sessions, five times a week, for 4 months. Moderate AET consisted of 60 min sessions, three times a week for 4 months. AET (-10 +/- 2 bursts/min, p = 0.03) and IMT + AET (-13 +/- 4 bursts/min, p = 0.007) reduced MSNA. These responses in MSNA were not different between AET and IMT + AET groups. IMT (0.22 +/- 0.08 mL/min/100 mL, p = 0.03), AET (0.27 +/- 0.09 mL/min/100 mL, p = 0.01), and IMT + AET (0.35 +/- 0.12 mL/min/100 mL, p = 0.008) increased forearm blood flow. No differences were found between groups. AET (3 +/- 1 mL/kg/min, p = 0.006) and IMT+AET (4 +/- 1 mL/kg/min, p = 0.001) increased peak oxygen consumption. These responses were similar between these groups. IMT (20 +/- 3 cmH2 O, p = 0.005) and IMT+AET (18 +/- 3 cmH2O, p = 0.01) increased maximal inspiratory pressure. No significant changes were observed in the NT group. CONCLUSIONS: IMT+AET causes no additive effects on neurovascular control in patients with heart failure with reduced ejection fraction compared with AET alone. These findings may be, in part, because few patients had inspiratory muscle weakness.

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