Automatic positive airway pressure for obstructive sleep apnea in heart failure with reduced ejection fraction

Abstract

Background: Moderate-to-severe obstructive sleep apnea (OSA) is highly prevalent in heart failure patients with reduced left ventricular ejection fraction (HFrEF), and is associated with worsening cardiac function and increased mortality.

Objectives: The automatic positive airway pressure (APAP) trial tested the impact of APAP treatment on changes for the pre-specified endpoints: changes in peak oxygen uptake (peak VO₂), percent-predicted peak VO₂ and oxygen uptake at anaerobic threshold (VO₂-AT).

Methods: This randomized, controlled pilot study included patients with chronic, stable HFrEF who had moderate-to-severe OSA. Patients were randomized 1:1 to either APAP (AutoSet™, ResMed) or nasal strips (control) for 6 months.

Results: 76 patients have been randomized and 58 had complete data for final analysis. There was a statistically significant change in the APAP intervention arm for the primary endpoint percent-predicted peak VO₂ in comparison to control (67 ± 17 to 73 ± 19%; p = 0.01). Additional primary endpoints peak VO₂ and VO₂-AT showed a trend in increase in the APAP group. Moreover, there were significant improvements within the APAP group for hypoxemia, left ventricular function and quality of life from baseline to 6 months, but not within the control group (p = 0.001 and p = 0.037, respectively).

Conclusion: APAP intervention was shown to significantly improve outcome compared to control group, represented in percent-predicted peak VO₂, an established surrogate marker for cardiovascular prognosis in HFrEF. APAP has additional beneficial effects on hypoxemia, cardiac function and quality of life.

Keywords: Heart failure with reduced ejection fraction; Obstructive sleep apnea; Positive airway pressure; Sleep-disordered breathing.

Fig. 1

Study design and key finding. Intervention through APAP therapy for 6 months significantly improved primary endpoint percent-predicted peak VO₂ in HFrEF patients with confirmed moderate-to-severe obstructive sleep apnea. APAP automatic positive airway pressure, HFrEF heart failure with reduced ejection fraction, OSA obstructive sleep apnea, Peak VO₂ peak oxygen consumption

Fig. 2

Patient flow. APAP automatic positive airway pressure, CPX cardiopulmonary exercise testing, HFrEF heart failure with reduced ejection fraction, OSA obstructive sleep apnea, PSG polysomnography, SDB sleep-disordered breathing. Exclusion criteria were: cardiac resynchronization therapy within the last 12 weeks, significant chronic obstructive pulmonary disease (forced expiratory volume in 1 s/vital capacity < 70%), respiratory insufficiency requiring home oxygen therapy, hypercapnia (pCO₂ > 45 mmHg), current treatment with any kind of positive airway pressure therapy, relevant treatment-emergent central sleep apnea (complex sleep apnea), restless legs syndrome (untreated or non-treatable), any cardiac surgery and/or percutaneous coronary intervention within the last 12 weeks, myocardial infarction (STEMI and non-STEMI), unstable angina or any kind of stroke within the last 12 weeks, acute myocarditis within the last 12 weeks, pregnancy or breast feeding