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Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure

Sands, SA; Mebrate, Y; Edwards, BA; Nernati, S; Manisty, CH; Desai, AS; Wellman, A; ... Malhotra, A; + view all (2017) Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure. American Journal of Respiratory and Critical Care Medicine , 195 (2) pp. 237-246. 10.1164/rccm.201604-07610C. Green open access

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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.

Type: Article
Title: Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure
Open access status: An open access version is available from UCL Discovery
DOI: 10.1164/rccm.201604-07610C
Publisher version: https://doi.org/10.1164/rccm.201604-07610C
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: 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
URI: http://discovery.ucl.ac.uk/id/eprint/10046584
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