Elevated sympathetic-mediated vasoconstriction at rest but intact functional sympatholysis during exercise in heart failure with reduced ejection fraction

Abstract

Background: Patients with heart failure with reduced ejection fraction (HFrEF) have exaggerated sympathoexcitation and impaired peripheral vascular conductance. Evidence demonstrating consequent impaired functional sympatholysis is limited in HFrEF. This study aimed to determine the magnitude of reduced limb vascular conductance during sympathoexcitation and whether functional sympatholysis would abolish such reductions in HFrEF. Methods: Twenty patients with HFrEF and 22 age-matched controls performed the cold pressor test (left foot 2-min in -0.5[1] °C water) alone (CPT) and with right handgrip exercise (EX+CPT). Right forearm vascular conductance (FVC), forearm blood flow (FBF), and mean arterial pressure (MAP) were measured. Results: Patients with HFrEF had greater decreases in %ΔFVC and %ΔFBF during CPT (both P<0.0001) but not EX+CPT (P=0.449, P=0.199) compared to controls, respectively. %ΔFVC and %ΔFBF decreased from CPT to EX+CPT in patients with HFrEF (both P<0.0001) and controls (P=0.018, P=0.015), respectively. MAP increased during CPT and EX+CPT in both groups (all P<0.0001). MAP was greater in controls compared to patients with HFrEF during EX+CPT (P=0.025) but not CPT (P=0.209). Conclusions: Acute sympathoexcitation caused exaggerated peripheral vasoconstriction and reduced peripheral blood flow in patients with HFrEF. Handgrip exercise abolished sympathoexcitatory-mediated peripheral vasoconstriction and normalized peripheral blood flow in patients with HFrEF. These novel data reveal intact functional sympatholysis in the upper limb and suggest exercise-mediated, local control of blood flow is preserved when cardiac limitations that are cardinal to HFrEF are evaded with dynamic handgrip exercise.