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

Authors

• Susan Redline
• Dongdong Li
• Shahrokh Javaheri
• Sanjay R Patel
• Sairam Parthasarathy
• James C Fang
• Lee K Brown
• Mark Dunlap
• M Safwan Badr
• Neomi Shah
• Luqi Chi
• Ruckshanda Majid
• Mihaela Teodorescu
• Garrick Stewart
• Eileen Hsich
• Tamar Polonsky
• Justin Vader
• Maryl R Johnson
• Dennis Auckley
• Henry Klar Yaggi
• Andrew Kao
• Ali Azarbarzin
• Raichel Alex
• Michael Rueschman
• Lisa Wolfe
• Daniel J Gottlieb
• Scott A Sands
• Phyllis C Zee
• Reena Mehra
• Babak Mokhlesi
• Rami Khayat
• Eldrin F Lewis
• William T Abraham
• Rui Wang

Language

English

Publication Date

12-1-2025

Journal

Annals of the American Thoracic Society

DOI

10.1513/AnnalsATS.202504-409OC

PMID

40929650

PMCID

PMC12700247

PubMedCentral® Posted Date

12-1-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Rationale: There are insufficient data to inform the management of central sleep apnea (CSA) in patients with heart failure with reduced ejection fraction (HFrEF). Nocturnal oxygen therapy (NOT) has been postulated to benefit CSA patients with HFrEF but has not been rigorously studied. Objectives: To compare NOT with sham NOT (control) in heart failure (HF) patients receiving guideline-based HF therapy on the composite outcome of first occurrence of either mortality due to any cause, a lifesaving cardiovascular intervention, or an unplanned hospitalization for worsening HF, together with other secondary outcomes.

Methods: A multisite, double-blind, sham-controlled randomized clinical trial was conducted from September 2019 to December 2021, when the study was terminated prematurely because of slow enrollment. Cox proportional-hazards regression models were used to analyze time-to-event outcomes.

Results: Ninety-eight participants (mean left ventricular ejection fraction, 27.8 ± 9.6%; mean central apnea-hypopnea index, 30.6 ± 18.2 events/h) 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 comparing the NOT group with the control group according to time to first event, adjusted for the stratification factor (hospitalization for HF in the past 12 mo and/or elevated outpatient brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide concentration) was 1.46 (95% confidence interval, 0.65-3.29). No group differences in changes in patient-reported outcomes (HF-specific quality of life [Kansas City Cardiomyopathy Questionnaire], sleep disturbance and sleep-related impairment [Patient-reported Outcomes Measurement Information System], generic health [EQ-5D], or mood [Patient Health Questionnaire-8]) were observed at 6 months. Polysomnography showed improved indices of sleep-disordered breathing (apnea-hypopnea index, central apnea-hypopnea index, and time at oxygen saturation < 90%) with oxygen compared with room air.

Conclusions: Although 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. Clinical trial registered with www.clinicaltrials.gov (NCT03745898).

Keywords

Humans, Sleep Apnea, Central, Heart Failure, Male, Double-Blind Method, Female, Oxygen Inhalation Therapy, Middle Aged, Aged, Stroke Volume, Quality of Life, Treatment Outcome, Polysomnography

Published Open-Access

yes

Recommended Citation

Redline, Susan; Li, Dongdong; Javaheri, Shahrokh; et al., "Nocturnal Oxygen Therapy for Central Sleep Apnea in Patients with Heart Failure: A Multisite, Double-Blind, Sham-controlled Randomized Clinical Trial (LOFT-HF)" (2025). Faculty, Staff and Student Publications. 3643.
https://digitalcommons.library.tmc.edu/uthmed_docs/3643