Modulation of ventilatory reflex control by cardiac resynchronization therapy

Abstract

Background: Heart failure (HF) is characterized by heightened sensitivities of the CO2 chemoreflex and the ergoreflex which promote increased ventilatory drive manifested as increased minute ventilation per volume of expired CO2 (VE/VCO2). The aims of this study were to evaluate the effects of cardiac resynchronization therapy (CRT) on carbon dioxide (CO2) chemosensitivity and the arterial CO2 setpoint.

Methods and results: Consecutive HF patients (n = 35) who underwent clinically indicated CRT were investigated by means of cardiopulmonary exercise testing and CO2 chemosensitivity evaluation with the use of a rebreathe method before and 4-6 months after CRT. Pre- and post-CRT measures were compared with the use of either paired t test or Wilcoxon test. Decreased peak VE/VCO2 (44 ± 10 vs 40 ± 8; P < .01), CO2 chemosensitivity (2.2 ± 1.1 vs 1.7 ± 0.8 L min(-1) mm Hg(-1); P = .04), and increased peak end-tidal CO2 (29 ± 5 vs 31 ± 5 mm Hg; P < .01) were also observed after CRT. Multivariate analysis adjusted for age and sex showed the decrease of peak VE/VCO2 from before to after CRT to be most strongly associated with the increase of peak end-tidal CO2 (β = -0.84; F = 21.5; P < .0001).

Conclusions: Decrease of VE/VCO2 after CRT is associated with decreased CO2 chemosensitivity and increase of the arterial CO2 setpoint, which is consistent with decreased activation of both the CO2 chemoreflex and the ergoreflex.

Keywords: Heart failure; cardiopulmonary exercise testing; chemosensitivity; pacing.

Conflict of interest statement

Conflict of interest: Dr. Somers has served as a Consultant for ResMed, Cardiac Concepts, Glaxo Smith Kline, Sepracor, Deshum, Respicardia and Medtronic Corporation and has been a principal investigator or co-investigator on research grants funded by the Respironics Foundation, the ResMed Foundation and the Sorin Corporation.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1

Relation of V̇E/V̇CO2 and VD/VT pre- and post-CRT. Slopes of ventilatory efficiency (V̇E/V̇CO2) and ratio of tidal volume to dead space (VD/VT) at 50% peak exercise are compared pre- and post-CRT. The shift of the slope of this relationship from pre- to post-CRT is consistent with observed decreased CO2 chemosensitivity, increased PETCO2 and reduced ventilatory drive.

Figure 2

Relation of V̇E/V̇CO2 and PETCO2 pre- and post-CRT. Slopes of ventilatory efficiency (V̇E/V̇CO2) to end-tidal carbon dioxide pressure (PETCO2) at 50% peak exercise are compared pre- and post-CRT. The lack of change of the slope of this relationship from pre- to post-CRT is consistent with no change of the VD/VT ratio and no change of ventilation-perfusion matching.