Studies of sleep-disordered breathing in heart failure

SERVE-HF54 (Treatment of Sleep-Disordered Breathing With Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure)
Aim: To determine whether adaptive servo-ventilation, a form of noninvasive ventilation that automatically adjusts to give the right amount of inspiratory pressure support upon inhalation, vs standard therapy alone could decrease morbidity and mortality in heart failure with reduced ejection fraction and predominantly central sleep apnea as was suggested by a post hoc analysis of a previous trial.52
Design: Multicenter, single-blind randomized controlled trial, N = 1,325
Primary end point: Composite end point of time to event for death from any cause, lifesaving cardiovascular intervention (transplant, left ventricular assist device, defibrillation), or unplanned hospitalization for heart failure over 5 years.
Findings: Not only was there no significant change in the primary end point, the treatment arm actually showed a significant increase in cardiovascular (hazard ratio 1.34, P= .0006) and all-cause (hazard ratio 1.28, P= .01) mortality. One prominent but hotly debated hypothesis is that the Cheyne-Stokes respirations in central sleep apnea are compensatory in severe heart failure, perhaps allowing the pulmonary musculature to rest, attenuating sympathetic nervous system activity, and avoiding acidosis due to hypercapnia.
SAVE56 (Sleep Apnea Cardiovascular Endpoints)
Aim: To determine whether continuous positive airway pressure (CPAP) plus standard therapy vs standard therapy alone would decrease cardiovascular events in patients with moderate to severe obstructive sleep apnea and known coronary or cerebrovascular disease.
Design: Multicenter, randomized controlled trial, N = 2,717
Primary end point: Composite end point of death from cardiovascular cause, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack over nearly 4 years.
Secondary end points: Cardiovascular secondary end points included the individual components of the primary composite end point, other composites of cardiovascular events, revascularization procedures, new-onset atrial fibrillation, new-onset diabetes mellitus, and death from any cause. Noncardiovascular end points included daytime sleepiness, snoring, mood (depression, anxiety), and quality-of-life scores.
Findings: Contrary to prior observational studies and despite a marked improvement in apneic-hypopneic events with CPAP (29/hour to 3.7/hour), no significant difference in the primary composite end point (17% vs 15.4%, P= .34) or cardiovascular secondary end points was evident. Significant improvement was seen in the noncardiovascular secondary end points such as daytime sleepiness, snoring, mood (depression, anxiety), and quality-of-life scores.