PURPOSE:In heart failure with reduced ejection fraction (HFrEF), the effects of automatic positive airway pressure therapy (APAP) for obstructive sleep apnea (OSA) on sleep quality and sympatho-vagal balance (SVB) are unknown. METHODS:In this randomized controlled trial (6 months of APAP vs. nasal strips as control), sleep quality and SVB in patients with HFrEF and OSA were monitored. The distinction was made between different breathing conditions (5-min segments of OSA or normal breathing [NB] during stable N2 sleep) at baseline (T0), APAP initiation (T1), and 6 months of successful APAP treatment (T2). RESULTS:Of 75 patients enrolled, 61 were men with average age of 65 ± 12 years and LVEF of 31 ± 9%; 37 patients were randomized into the APAP and 38 into the control (nasal strips only) group. At T0, OSA was associated with a 17% increase in the low-frequency/high-frequency component ratio of heart rate variability (LF/HF) versus baseline, suggesting an increase in sympathetic drive (SVB) with OSA compared with normal breathing. Respiratory indices and oxygen saturation all significantly improved at both T1 and T2, but at 6 months, APAP had no clinically relevant effect on objective sleep quality versus control. In fact, in patients with HFrEF (n = 23 with data suitable for HRV analysis), there was even a trend (p = 0.097) towards an additional 17% increase in LF/HF at T2 in the therapy group, suggesting (undesired) increased SVB in the APAP group. CONCLUSION:Treatment of OSA in patients with systolic HF improves respiratory indices but does not have a favorable effect on sleep quality. While OSA per se was associated with an increase in sympathetic drive, APAP treatment was not associated with a reduction in sympathetic drive. After 6 months of treatment, there was even a trend towards additional increases in sympathetic drive in the APAP group.