BACKGROUND: We previously showed in heart failure (HF) patients that obstructive respiratory events during sleep and generation of negative intrathoracic pressure during Mueller manoeuvres, mimicking obstructive apneas, acutely reduced stroke volume (SV). We also showed that treating obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) increased left ventricular ejection fraction over a 1-month period. We therefore hypothesized that, in HF patients, those with OSA would have greater overnight declines in SV and cardiac output (CO) than in those without sleep apnea, and that therapy of OSA using CPAP would prevent these declines. METHODS: We examined overnight percent change in SV and CO in 32 HF patients with and 28 without OSA using digital photoplethysmography. Among patients with OSA, we also examined changes in SV and CO during a CPAP titration study. RESULTS: During the baseline polysomnogram SV and CO decreased more overnight in those with OSA than in those without sleep apnea (-12.6 ± 7.7% vs -3.2 ± 6.8%; P < 0.001 and -16.2 ± 9.9% vs -3.7 ± 8.3%; P < 0.001, respectively). Overnight changes in SV and CO correlated inversely with total apnea-hypopnea index (r = -0.551; P < 0.001 and r = -0.522; P < 0.001, respectively). In 21 patients with OSA, CPAP reduced the total apnea-hypopnea index from 37.7 ± 21.4 to 15.0 ± 16.0 (P < 0.001) in association with attenuation of the overnight reduction of SV (from -14.0 ± 7.9% to -3.4 ± 9.8%; P = 0.002) and CO (from -17.2 ± 9.0% to -9.7 ± 10.7%; P = 0.042). CONCLUSIONS: In patients with HF, coexisting OSA causes overnight declines in SV and CO that are prevented through reversal of OSA by CPAP.