Training heart failure patients with reduced ejection fraction attenuates muscle sympathetic nerve activation during mild dynamic exercise

Muscle sympathetic nerve activity (MSNA) decreases during low intensity dynamic 1-leg exercise in healthy subjects but increases in patients with heart failure with reduced ejection fraction (HFrEF). AIMS: We hypothesized that increased peak oxygen uptake (V̇O2peak) after aerobic training would be accompanied by less sympatho-excitation during both mild and moderate 1-leg dynamic cycling; an attenuated muscle metaboreflex; and greater skin vasodilation. METHODS: We studied 27 stable, treated HFrEF patients (6 women; mean age 65 ± 2 SE years; mean left ventricular ejection fraction 30 ± 1%) and 18 healthy age-matched volunteers (6 women; mean age 57 ± 2). We assessed V̇O2peak (open-circuit spirometry); and the skin microcirculatory response to reactive hyperemia (laser flowmetry). Fibular MSNA (microneurography) was recorded before and during 1-leg cycling (2 min unloaded and 2 min at 50% of V̇O2peak ) and, to assess the muscle metaboreflex, during post-handgrip ischemia (PHGI). HFrEF patients were evaluated before and after 6 months of exercise-based cardiac rehabilitation. RESULTS: Pre-training V̇O2peak and skin vasodilatation were lower (P<0.001) and resting MSNA higher ( P=0.01) in HFrEF than control subjects. Training improved V̇O2peak (+3.0±1.0 ml·kg-1∙min-1; P<0.001) and cutaneous vasodilation and diminished resting MSNA (-6.0±2.0, P=0.01) plus exercise MSNA during unloaded (-4.0±2.5, P=0.04) but not loaded cycling (-1.0±4.0 bursts/min, P=0.34) and MSNA during PHGI ( P<0.05). CONCLUSIONS: In HFrEF patients, exercise training lowers MSNA at rest, desensitizes the sympatho-excitatory metaboreflex, and diminishes MSNA elicited by mild but not moderate cycling. Training-induced downregulation of resting MSNA and attenuated reflex sympathetic excitation may improve exercise capacity and survival.