LOW-FLOW NOCTURNAL OXYGEN THERAPY FOR THE TREATMENT OF CENTRAL SLEEP APNEA IN CHRONIC HEART FAILURE: THE PAST, the PRESENT, and the FUTURE

Abstract Central sleep apnea (CSA), commonly seen in patients with heart failure and reduced ejection fractions (HFrEF), is associated with hypoxia, heightened sympathetic activity, and poor clinical outcomes. While several CSA therapies reduce the apnea-hypopnea index, none have been shown to improve long-term important clinical outcomes. Nocturnal oxygen therapy (NOT) represents a physiologically sound approach to the treatment of CSA. Evidence supports the potential benefits of NOT in such patients, but no proof of its effectiveness on hard outcomes exists. Thus, there has been a longstanding need for a randomized controlled trial of NOT for CSA in HFrEF patients. The ideal trial would establish the rationale for NOT by measuring clinically meaningful outcomes, use rigorous methodologies such as double-blinding and a sham control, and optimize safety by delivering oxygen at doses that ameliorate hypoxemia and avoid hyperoxia. Such a trial (LOFT-HF NCT03745898) was indeed eventually sponsored by the National Institute of Heath and was initiated in 2018-2019. However, the trial was halted during the COVID-19 pandemic due to slow enrollment. Findings were recently published and did not provide a firm conclusion but suggested potential harm in the NOT arm based on a very small number of participants. Meanwhile, the American Academy of Sleep Medicine (AASM) published recently new treatment guidelines for CSA, suggesting use NOT in CSA. In this article, we attempt to reconcile the LOFT-HF trial findings with existing literature and the new AASM CSA management guidelines and discuss future research needs.