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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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 ClinicalTrials.gov number, NCT00733343.).

Figure 1. Randomization, Treatment, and Follow-up of the Patients

Patients who withdrew consent did so for both study participation and follow-up (see the Supplementary Appendix). Of the 73 patients who withdrew consent in the control group, 3 had started adaptive servo-ventilation (ASV), and of the 82 who withdrew consent in the ASV group, 2 had discontinued ASV. CPAP denotes continuous positive airway pressure, and PAP positive airway pressure.

Figure 2. Cumulative Incidence Curves for the Primary End Point, Death from Any Cause, and Cardiovascular Death

The primary end point was a composite of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a long-term ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate shock for ventricular arrhythmia in patients with an implantable cardioverter–defibrillator), and unplanned hospitalization for worsening chronic heart failure.