Sympathetic Response to 1-Leg Cycling Exercise Predicts Exercise Capacity in Patients with Heart Failure with Preserved Ejection Fraction

BACKGROUND: In heart failure, sympathetic excess and exercise intolerance impair quality of life. In heart failure with reduced ejection fraction, exercise stimulates a reflex increase in muscle sympathetic nerve activity (MSNA) that relates inversely to peak oxygen uptake (VO2peak). Whether similar sympathoexcitatory responses are present in heart failure with preserved EF (HFpEF) and relate to VO2peak are unknown. METHODS: In 13 patients with HFpEF (70±6 years), 17 comorbidity-matched controls (CMC; 67±8 years), and 18 healthy controls (65±8 years), we measured heart rate, blood pressure, and MSNA (microneurography) during (1) 7-minute baseline; (2) 2-minute isometric handgrip (40% maximal voluntary contraction) or rhythmic handgrip (50% and 30% maximal voluntary contraction) exercise, followed by 2-minute postexercise circulatory occlusion; and (3) 4-minute 1-leg cycling (2 minutes each at mild and moderate intensity). VO2peak was obtained by open-circuit spirometry. RESULTS: Resting MSNA was higher and VO2peak was lower in HFpEF versus CMCs and healthy controls (all P<0.05). During handgrip, MSNA increased in all groups (all P<0.05); in HFpEF, MSNA was greater than CMCs and healthy controls during HG and postexercise circulatory occlusion at 40% isometric handgrip (all P<0.05) and HG only at 50% and 30% rhythmic handgrip (all P<0.05). During cycling, MSNA (bursts·min-1) decreased during mild (-4±4; P=0.01) and moderate (-8±6; P<0.001) cycling in healthy controls, was unchanged during mild (+1±7; P=0.42) and moderate (+2±8; P=0.28) cycling in CMCs, yet increased in HFpEF during mild (+8±8; P<0.001) and moderate (+9±10; P<0.001) cycling. In HFpEF, the change in MSNA during moderate cycling related inversely to relative (r=-0.72; R 2=0.51; P<0.01) and percent-predicted (r=-0.63; R 2=0.39; P=0.03) VO2peak. No statistically significant relationships were detected in controls (P>0.05). CONCLUSIONS: In contrast to CMCs, patients with HFpEF exhibit augmented MSNA at rest and during exercise. The magnitude of such paradoxical sympathoexcitation during dynamic cycling relates inversely to VO2peak, consistent with a neurogenic, vasoconstrictor limit on exercise capacity in HFpEF.