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

Scott Sands, Bradley Edwards, Kirk Keh Huat Kee, Anthony Turton, Elizabeth Skuza, Teanua Roebuck, Denise O'Driscoll, Garun Hamilton, Matthew Naughton, Philip Berger

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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 = 2pi/(2piDR - sin2piDR) 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.
Original languageEnglish
Pages (from-to)1067 - 1075
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number9
Publication statusPublished - 2011

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