Resonance as the mechanism of daytime periodic breathing in patients with heart failure
File(s)
Author(s)
Type
Journal Article
Abstract
Rationale: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited.
Objectives: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance “strength”) rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects.
Methods: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation.
Measurements and Main Results: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain—consequent to increased chemosensitivity and delay—the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = −0.68) oscillations (P < 0.001 for all, both groups combined).
Conclusions: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population.
Objectives: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance “strength”) rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects.
Methods: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation.
Measurements and Main Results: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain—consequent to increased chemosensitivity and delay—the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = −0.68) oscillations (P < 0.001 for all, both groups combined).
Conclusions: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population.
Date Issued
2017-01-15
Date Acceptance
2016-08-25
Citation
American Journal of Respiratory and Critical Care Medicine, 2017, 195 (2), pp.237-246
ISSN
1073-449X
Publisher
American Thoracic Society
Start Page
237
End Page
246
Journal / Book Title
American Journal of Respiratory and Critical Care Medicine
Volume
195
Issue
2
Copyright Statement
© 2017 by the American Thoracic Society.
Sponsor
British Heart Foundation
St Mary's Coronary Flow Trust
Foundation for Circulatory Health
British Heart Foundation
Foundation for Circulatory Health
British Heart Foundation
Grant Number
FS/04/079
Nil
ICCH/05/5004
PG/07/065
ICCH/07/5017
FS/10/38/28268
Subjects
Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
instability
loop gain
Cheyne-Stokes respiration
heart failure
chemosensitivity
CHEYNE-STOKES RESPIRATION
CENTRAL SLEEP-APNEA
EXERCISE OSCILLATORY VENTILATION
CLINICAL-IMPLICATIONS
PROGNOSTIC VALUE
LOOP GAIN
VARIABILITY
CHEMOSENSITIVITY
STABILITY
INSTABILITY
Publication Status
Published
Date Publish Online
2016-08-25