Loop gain as a means to predict a positive airway pressure suppression of Cheyne-Stokes respiration in patients with heart failure

Am J Respir Crit Care Med. 2011 Nov 1;184(9):1067-75. doi: 10.1164/rccm.201103-0577OC.


Rationale: Patients with heart failure (HF) and Cheyne-Stokes respiration or periodic breathing (PB) often demonstrate improved cardiac function when treatment with continuous positive airway pressure (CPAP) resolves PB. Unfortunately, CPAP is successful in only 50% of patients, and no known factor predicts responders to treatment. Because PB manifests from a hypersensitive ventilatory feedback loop (elevated loop gain [LG]), we hypothesized that PB persists on CPAP when LG far exceeds the critical threshold for stable ventilation (LG = 1).

Objectives: To derive, validate, and test the clinical utility of a mathematically precise method that quantifies LG from the cyclic pattern of PB, where LG = 2π/(2πDR - sin2πDR) and DR (i.e., duty ratio) = (ventilatory duration)/(cycle duration) of PB.

Methods: After validation in a mathematical model of HF, we tested whether our estimate of LG changes with CPAP (n = 6) and inspired oxygen (n = 5) as predicted by theory in an animal model of PB. As a first test in patients with HF (n = 14), we examined whether LG predicts the first-night CPAP suppression of PB.

Measurements and main results: In lambs, as predicted by theory, LG fell as lung volume increased with CPAP (slope = 0.9 ± 0.1; R(2) = 0.82; P < 0.001) and as inspired-arterial PO(2) difference declined (slope = 1.05 ± 0.12; R(2) = 0.75; P < 0.001). In patients with HF, LG was markedly greater in 8 CPAP nonresponders versus 6 responders (1.29 ± 0.04 versus 1.10 ± 0.01; P < 0.001); LG predicted CPAP suppression of PB in 13/14 patients.

Conclusions: Our novel LG estimate enables quantification of the severity of ventilatory instability underlying PB, making possible a priori selection of patients whose PB is immediately treatable with CPAP therapy.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Cheyne-Stokes Respiration / diagnosis
  • Cheyne-Stokes Respiration / etiology
  • Cheyne-Stokes Respiration / mortality
  • Cheyne-Stokes Respiration / physiopathology
  • Cheyne-Stokes Respiration / prevention & control*
  • Continuous Positive Airway Pressure*
  • Feedback, Physiological
  • Heart Failure / complications
  • Heart Failure / diagnosis
  • Heart Failure / mortality
  • Heart Failure / physiopathology*
  • Heart Failure / therapy*
  • Humans
  • Models, Animal
  • Oxygen Consumption
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Tidal Volume
  • Treatment Outcome