Heart failure-specific inverse relationship between the muscle sympathetic response to dynamic leg exercise and V̇O2peak.

During 1-leg cycling, contralateral muscle sympathetic nerve activity (MSNA) falls in healthy adults but increases in most with reduced ejection fraction heart failure (HFrEF). We hypothesized that their peak oxygen uptake (VO2peak) relates inversely to their MSNA response to exercise. Twenty-nine patients (6 women; 63±9 years; LVEF: 30±7%; VO2peak: 78±23 percent age-predicted (%VO2peak); mean±SD) and 21 healthy adults (9 women; 58±7 years; 115±29% VO2peak) performed 2-mins of mild- ("loadless") and moderate-intensity ("loaded") 1-leg cycling. Heart rate (HR), blood pressure (BP), contralateral leg MSNA and perceived exertion rate (RPE) were recorded. Resting MSNA burst frequency (BF) was higher (p<0.01) in HFrEF (51±11 vs 44±7 bursts∙min-1). Exercise HR, BP and RPE responses at either intensity were similar between groups. In minute two of "loadless" and "loaded" cycling, group mean BF fell from baseline values in controls (-5±6 and -7±7 bursts∙min-1, respectively) but rose in HFrEF (+5±7 and +5±10 bursts∙min-1). However, in 10 of the latter cohort, BF fell, similarly to controls. An inverse relationship between ΔBF from baseline to "loaded" cycling and %VO2peak was present in patients (r=-0.43, p<0.05), absent in controls (r=0.07, p=0.77). In HFrEF, ~18% of variance in %VO2peak can be attributed to the change in BF elicited by exercise. Novelty Bullets: • Unlike healthy individuals, in the majority of heart failure patients with reduced ejection fraction (HFrEF), 1-leg cycling increases muscle sympathetic nerve activity (MSNA). • In HFrEF, ~18% of age-predicted peak oxygen uptake (VO2peak) can be attributed to changes in MSNA elicited by low-intensity exercise. • This relationship is absent in healthy adults.