Monahan et al demonstrated that patients with severe obstructive sleep apnea (OSA) are less likely to respond to antiarrhythmic drug (AAD) therapy for atrial fibrillation (AF) than those with milder forms of OSA. Interestingly, nonresponders to AADs had higher apnea-hypopnea indexes than responders. Minimum oxygen saturation did not differ between the 2 groups. This suggests that not hypoxia but the obstructive events seem to be important for AF recurrence, limiting AAD efficacy in patients with OSA.

Previously, our group showed in a pig model of OSA that forced inspiration against the obstructed upper airways results in substantial negative tracheal pressure (NTP) down to −60 to −80 mbar, representing a strong trigger for AF compared to hypoxia alone. Applied strong NTP causes a pronounced shortening of the atrial effective refractory period and increased susceptibility to AF. NTP-induced atrial effective refractory period shortening was modulated by atropine or atenolol, which emphasizes the importance of autonomic imbalance in OSA-associated AF. Importantly, this atrial proarrhythmogenic effect of NTP was not prevented by class III AADs such as amiodarone or sotalol. This finding is completely in line with the findings of Monahan et al and may explain the failure of AADs in patients with OSA.

Obstructive respiratory events create a highly arrhythmogenic substrate in the atrium that is difficult to suppress using available AADs and differs significantly from other conditions for which AADs have shown sufficient efficacy. This factor should be considered during the development of future antiarrhythmic pharmacologic and interventional treatment strategies for AF. Interestingly, modulation of the autonomic nervous system by renal sympathetic denervation or ablation of atrial ganglionated plexi displayed antiarrhythmic effects of 2 different animal models for obstructive and central sleep apnea and deserves to be tested in clinical studies.