Central Command and the Regulation of Exercise Heart Rate Response in Heart Failure With Preserved Ejection Fraction.

Abstract

Chronotropic incompetence is common in heart failure with preserved ejection fraction (HFpEF) and is linked to impaired aerobic capacity. Whether upstream autonomic signaling pathways responsible for raising exercise heart rate are impaired in HFpEF is unknown. We investigated the integrity of central command and muscle metaboreceptor function, 2 predominant mechanisms responsible for exertional increases in heart rate, in patients with HFpEF and senior controls. Fourteen healthy senior controls (7 men, 7 women) and 20 carefully screened patients with HFpEF (8 men, 12 women) underwent cardiopulmonary exercise testing (peak Vo₂) and static handgrip exercise at 40% of maximal voluntary contraction to fatigue with postexercise circulatory arrest for 2 minutes to assess central command and metaboreceptor function, respectively. Peak Vo₂ (13.1±3.4 versus 22.7±4.0 mL/kg/min; <i>P</i><0.001) and heart rate (122±20 versus 155±14 bpm; <i>P</i><0.001) were lower in patients with HFpEF than senior controls. There were no significant differences in peak heart rate response during static handgrip between groups (patients with HFpEF versus controls: 90±13 versus 93±10 bpm; <i>P</i>=0.49). Metaboreceptor function, defined as mean arterial blood pressure at the end of postexercise circulatory arrest, was not significantly different between groups. Central command (vagally mediated) and metaboreceptor function (sympathetically mediated) in patients with HFpEF were not different from those in healthy senior controls despite significantly lower peak whole-body exercise heart rates. These results demonstrate key reflex autonomic pathways regulating exercise heart rate responsiveness are intact in HFpEF.