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N Engl J Med. 2015 Sep 17;373(12):1095-105. doi: 10.1056/NEJMoa1506459. Epub 2015 Sep 1.

Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure.

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From Imperial College London (M.R.C) and Royal Brompton Hospital (A.K.S.) - both in London; ResMed Science Center, ResMed Germany, Martinsried (H.W.), Sleep and Ventilation Center Blaubeuren, Respiratory Center Ulm, Ulm (H.W.), the Department of Medical Biometry and Epidemiology, University Medical Center Eppendorf, Hamburg (K.W.), the Department of Medicine I and Comprehensive Heart Failure Center, University Hospital and University of Würzburg, Würzburg (C.A.), Heart Center, University of Cologne, Cologne (E.E.), and the Department of Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital Essen, University Duisburg-Essen, Essen (H.T.) - all in Germany; University Paris Diderot, Sorbonne Paris Cité, Hôpital Bichat, Explorations Fonctionnelles, Département Hospitalo-Universitaire Fight Inflammation and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris (M-P.O.), Centre Hospitalier Universitaire (CHU) de Grenoble, Grenoble, (P.L.), and INSERM, Université de Lorraine, CHU de Nancy, Nancy (F.Z.) - all in France; and the Mayo Clinic and Mayo Foundation, Rochester, MN (V.K.S.).



Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea.


We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea-hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guideline-based medical treatment alone (control). The primary end point in the time-to-event analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure.


In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P=0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P=0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P=0.006).


Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF number, NCT00733343.).

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