BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is associated with cardiovascular disease. Preliminary studies suggested breathing improvement in patients with apnea and heart disease when atrial overdrive pacing was applied during sleep. However, more recent studies do not show significant beneficial effect for atrial overdrive pacing in OSA. To further investigate this relationship, we conducted a randomized clinical trial evaluating the effect of atrial overdrive pacing on sleep-related breathing events in subjects with OSA and systolic heart failure. PATIENTS AND METHODS: We screened 33 subjects with symptoms consistent with OSA. On a screening overnight polysomnography (PSG), 15 subjects with mean age of 74 years (standard deviation (SD) 6.6) and ejection fraction of 38% (SD 14.4%) had OSA defined as having an apnea/hypopnea index (AHI) of > or =15 per hour of sleep. These subjects underwent additional PSGs including a night with atrial overdrive pacing (O), a night with pacemaker rate set at 40-50 beats per minutes (N), and a positive airway pressure titration night. The O and N nights were consecutive and the order was randomized. For O, the pacemaker rate was set at 15 beats higher than the average nightly heart rate (determined from the screening night). RESULTS: At baseline, mean AHI was 34.8 (15.5) and mean SaO(2) nadir was 85% (3.2%). Average heart rate was significantly higher on O nights compared to N nights (p<0.005). The apnea index (AI) was statistically lower on O nights compared to N nights (18+/-16.6 vs. 24+/-18.9, p<0.05). However, AHI and minimum and average O(2) saturations did not differ significantly between O and N nights. Interestingly, AHI improved statistically significantly on O nights in younger subjects. CONCLUSIONS: While statistically reliable, the small pacing-related reduction in sleep-disordered breathing (SDB) events is of unknown clinical significance. By contrast, continuous positive airway pressure (CPAP) dramatically improved AHI, AI, respiratory arousal index, and O(2) saturation. Thus our data suggest that overdrive pacing exerts a mild effect on respiratory events in some heart failure patients with OSA; however, atrial overdrive pacing was not therapeutically effective for improving airway patency and sleep-related respiratory function.