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

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 CO 2 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 CO 2 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 = 20.68) 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.Keywords: instability; loop gain; Cheyne-Stokes respiration; heart failure; chemosensitivity

Breath‐holding as a means to estimate the loop gain contribution to obstructive sleep apnoea

“…Fourier transform analysis of ventilation and changes at this frequency described controller (Δventilation/Δ) and plant gains (Δ/Δventilation*; *ventilation, corrected for inspired , yields a ventilatory disturbance (Ghazanshahi & Khoo, ; Sands et al . ) as shown in Figs and (red dashed lines)). Overall loop gain equals controller × plant (Ghazanshahi & Khoo, ; Sands et al .…”

“…), a modification of the pseudo‐random binary stimulation approach (Ghazanshahi & Khoo, ; Sands et al . ). A gas mixture (6% CO 2 –14% O 2 ) was chosen to mimic alveolar gases and thereby simulate apnoea without disturbing the participant.…”

“…Pulses of hypoxic hypercapnia (20 s/3 min) stimulate the chemoreflex control system at several specific frequencies, including 1 cycle/min (Sands et al . ). Fourier transform analysis of ventilation and changes at this frequency described controller (Δventilation/Δ) and plant gains (Δ/Δventilation*; *ventilation, corrected for inspired , yields a ventilatory disturbance (Ghazanshahi & Khoo, ; Sands et al .…”

“…normal alveolar gas) (Sands et al . ) while on CPAP to maintain airway patency. We also sought evidence to confirm (1) the association between wake and sleep loop gain values, by additionally performing similar pulses during wakefulness, and (2) that breath‐holding measures also predicted steady‐state loop gain measured using CPAP dial‐ups during sleep.…”

Is It Possible to Distinguish Patients with Terminal Stage of Heart Failure by Analyzing Their Breathing Patterns?

“…20) According to a combination of mathematical modeling and direct measurement, daytime oscillatory breathing in heart failure is closely related to chemoreflex hypersensitivity and reduced stability that predicts mortality in patients with advanced heart failure. 21) Himi, et al concluded that cardiac function is more impaired in cardiac patients who manifest oscillatory breathing at rest and during exercise than in those who manifest oscillatory breathing only at rest or only during exercise. 20) The frequent occurrence of oscillatory breathing may be a more important indicator for severe heart failure, regardless of during exercise or at rest.…”