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

Abstract

Background: Chronotropic incompetence (CI) is common in HFpEF and is linked to impaired aerobic capacity. Whether upstream autonomic signaling pathways responsible for raising exercise heart rate (HR) are impaired in HFpEF is unknown. We investigated the integrity of central command and muscle metaboreceptor function, two predominant mechanisms responsible for exertional increases in HR, in HFpEF and senior control subjects. Methods: Fourteen healthy, senior controls (7M,7F) and 20 carefully screened HFpEF patients (8M,12F) underwent cardiopulmonary exercise testing (peak VO 2 ) and static handgrip exercise at 40% of maximal voluntary contraction (MVC) to fatigue with post-exercise circulatory arrest (PECA) for 2 minutes to assess central command and metaboreceptor function respectively. Results: Peak VO 2 (13.1 ± 3.4 vs 22.7 ± 4.0 ml/kg/min; p<0.001) and HR (122 ± 20 vs 155 ± 14 bpm; p<0.001) were lower in HFpEF than senior controls. There were no significant differences in peak HR response during static handgrip between groups (HFpEF vs controls: 90 ± 13 vs 93 ± 10 bpm; p=0.49). Metaboreceptor function defined as mean arterial blood pressure at the end of PECA was also not significantly different between groups. Conclusions: Central command (vagally mediated) and metaboreceptor function (sympathetically mediated) in patients with HFpEF were not different from 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.

Comparison of haemodynamic response to muscle reflex in heart failure with reduced vs. preserved ejection fraction

“…Sarma et al . noninvasively reported using PECA after 40% of MVC to fatigue that metabo‐receptor activity may be similar to that in healthy controls 26 . Roberto et al .…”

“…noninvasively reported using PECA after 40% of MVC to fatigue that metabo‐receptor activity may be similar to that in healthy controls. 26 Roberto et al . observed maintained MAP via an increase in SVR during PECA after dynamic handgrip at 30% of MVC, suggesting the muscle metabo‐reflex control of the haemodynamics in HFpEF patients.…”

“…Sarma et al noninvasively reported using PECA after 40% of MVC to fatigue that metabo-receptor activity may be similar to that in healthy controls. 26 Roberto et al observed maintained MAP via an increase in SVR during PECA after dynamic handgrip at 30% of MVC, suggesting the muscle metabo-reflex control of the haemodynamics in HFpEF patients. 27 In our HFpEF patients, the high LVESP, which was significantly increased by IHG exercise at 30% of MVC, was not maintained during PECA, suggesting lower metabo-reflex activity in HFpEF patients than in HFrEF patients.…”

Exercise testing in heart failure with preserved ejection fraction: an appraisal through diagnosis, pathophysiology and therapy – A clinical consensus statement of the Heart Failure Association and European Association of Preventive Cardiology of the European Society of Cardiology

“…The initial view that exercise limitation and symptoms are entirely due to an inadequate ventricular filling due to increased ventricular stiffness 13 has long ago been refuted. Patients with HFpEF exhibit a limited cardiac reserve on exercise 14 due to a multitude of factors including chronotropic incompetence, 15 impaired contractility, 16 atrial dysfunction, 17 atrial rhythm disorders (atrial fibrillation), 18 atrial functional mitral regurgitation 19 inducible ischaemia, 20,21 and unfavourable right ventricle to left ventricle interaction 22,23 …”

Autonomic cardiovascular reflex control of hemodynamics during exercise in heart failure with reduced ejection fraction and the effects of exercise training

“…In humans with severe HFrEF, the methodology was unable to differentiate between central command and the mechanoreflex as the primary driver of elevated MSNA during exercise [75]. Interestingly, central command in patients with HF and preserved ejection fraction (HFpEF) was not different from healthy controls despite a lower exercise heart rate [167]; however, the such investigations to better understand the role of central command on exercise pathophysiology in patients with HFrEF is lacking and merits further attention.…”