Nocturnal Oxygen Therapy for Central Sleep Apnea in Patients with Heart Failure: A Multi-site, Double-blind, Sham-controlled Randomized Clinical Trial (LOFT-HF)

Abstract

Rationale: There are insufficient data to inform the management of central sleep apnea (CSA) in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Nocturnal oxygen therapy (NOT) has been postulated to benefit CSA patients with HFrEF, but has not been rigorously studied. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Objectives: To compare NOT to sham-NOT (control) in HF patients receiving guideline-based heart failure therapy on the composite outcome of first occurrence of either mortality due to any cause, a life-saving cardiovascular intervention, or unplanned hospitalization for worsening heart failure, along with other secondary outcomes.

Methods: A multi-site, double-blind, sham-controlled randomized clinical trial was conducted from Sept 2019 to Dec 2021, when the study was terminated prematurely due to slow enrollment. Cox proportional hazards regression models were used to analyze time-to-event outcomes.

Measurements and main results: Ninety-eight participants (mean left ventricular ejection fraction: 27.8 ± 9.6%; central apnea hypopnea index: 30.6 ± 18.2 events/hr) were randomized and followed for an average of 10.8±6.3 months. A total of 22 events met the criteria for the primary composite endpoint. The hazard ratio (95% Confidence Interval [CI]) comparing the NOT group to the control group based on the time-to-first event, adjusted for the stratification factor (hospitalization for heart failure in the last 12 months and/or elevated outpatient brain natriuretic peptide (BNP) or NTproBNP level) was 1.46 (95% CI: 0.65, 3.29). No group difference in changes in patient-reported outcomes (heart-failure specific quality of life [Kansas City Cardiomyopathy Questionnaire], sleep disturbance and sleep related-impairment [Patient-Reported Outcomes Measurement Information System], generic health [EuroQol 5D]; or mood [Patient Health Questionnaire-8]) was observed at 6 months. Polysomnography showed improved indices of sleep-disordered breathing (apnea hypopnea index, central apnea hypopnea index, and time at oxygen saturation below 90%) with oxygen compared to room air.

Conclusions: While NOT improves CSA and overnight oxygenation, this prematurely terminated study does not provide support for the clinical effectiveness of NOT in patients with CSA and HFrEF. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).