Intervention: Oxygen
Trial phase: Phase 3
ATC code: V03AN01
SMILES: O=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 48
Group description: Active nocturnal oxygen therapy

Oxygen: Active nocturnal oxygen concentrator
Eligibility criteria:
Inclusion Criteria:

Aged ≥ 21 years at the date of consent.
History of chronic, stable heart failure with reduced ejection fraction with left ventricular ejection fraction (LVEF) ≤ 50% determined by echocardiography, radionuclide angiography, left ventriculography, or cardiac magnetic resonance imaging, within the year prior to enrollment.
Central sleep apnea, defined using as an apnea-hypopnea index (AHI) > 15/h with ≥ 50% central events (apnea and hypopneas).

New York Heart Association (NYHA) Class III or IV, or NYHA Class II with any of the following:

at least one hospitalization for heart failure within the 24 months prior to enrollment or;
a BMI corrected BNP ≥ 300 pg/ml or a corrected NT-proBNP ≥ 1500 pg/ml or;
an ED visit for HF exacerbation where the patient has received an IV diuretic within 12 months of enrollment.
Treatment with stable, optimized guideline-directed medical therapies (GDMT) according to applicable guidelines in the U.S. and Canada, where stable is defined as the addition of no new class of disease-modifying drug for ≥ 30 days prior to randomization (reasons for intolerance to GDNT must be documented).
In the investigator's opinion, willing and able to comply with all study requirements.
Able to fully understand study information and sign an Institutional Review Board (IRB) approved informed consent (including HIPAA authorization in the U.S.).

Exclusion Criteria:

Current positive airway pressure use or predominantly obstructive rather than central sleep apnea.
Oxygen saturation < 90% at rest during the day.
Nocturnal oxygen saturation < 88% for > 5 continuous minutes unaccompanied by apneas or hypopneas.
Chronic daytime or nighttime use of supplemental oxygen.
Participants and their bed-partners who currently smoke in the bedroom.
Severe pulmonary disease requiring continuous home oxygen therapy or the continuous or frequent intermittent use of oral steroids or documented severe chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1) < 50%.
Cardiac surgery, percutaneous coronary intervention, myocardial infarction or unstable angina within the previous 3 months.
Transient ischemic attack or stroke within the previous 3 months.
Cardiac resynchronization therapy implantation scheduled or performed within 3 months prior to randomization.
Primary hemodynamically-significant uncorrected valvular heart disease (obstructive or regurgitant) or any valvular disease expected to require surgery during the trial.
Acute myocarditis/pericarditis or other cause of potentially reversible cardiomyopathy (e.g., post-partum cardiomyopathy, tachycardia-induced cardiomyopathy), within the previous 6 months.
End-stage (Stage D) heart failure (HF) requiring continuous outpatient intravenous (IV) inotropic therapy, placement of ventricular assist device, listing for cardiac transplantation, or end-of-life care (e.g. hospice care).
Pregnancy or of child bearing potential without a negative pregnancy test within 10 days prior to enrollment.
Life expectancy < 1 year for diseases unrelated to chronic HF.
Enrolled or planning to enroll in another study that may conflict with protocol requirements or confound subject results in this trial.