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 (V̇O_2peak). Whether similar sympathoexcitatory responses are present in heart failure with preserved EF (HFpEF) and relate to V̇O_2peak 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). V̇O_2peak was obtained by open-circuit spirometry.

Results: Resting MSNA was higher and V̇O_2peak 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) V̇O_2peak. 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 V̇O_2peak, consistent with a neurogenic, vasoconstrictor limit on exercise capacity in HFpEF.