title: Loop gain as a means to predict a positive airway pressure suppression of Cheyne-Stokes respiration in patients with heart failure.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: The Ritchie Centre, Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia. sasands@partners.org
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sands
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Edwards
authors.forename: Kirk
authors.initials: K
authors.lastname: Kee
authors.forename: Anthony
authors.initials: A
authors.lastname: Turton
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Skuza
authors.forename: Teanau
authors.initials: T
authors.lastname: Roebuck
authors.forename: Denise M
authors.initials: DM
authors.lastname: O'Driscoll
authors.forename: Garun S
authors.initials: GS
authors.lastname: Hamilton
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Naughton
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Berger
mesh_terms: D000818:Animals; D002639:Cheyne-Stokes Respiration / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D045422:Continuous Positive Airway Pressure; D025461:Feedback, Physiological; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D023421:Models, Animal; D010101:Oxygen Consumption; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013990:Tidal Volume; D016896:Treatment Outcome