Mechanisms of Atrial Fibrillation in Obstructive Sleep Apnoea

Abstract

Obstructive sleep apnoea (OSA) is a strong independent risk factor for atrial fibrillation (AF). Emerging clinical data cite adverse effects of OSA on AF induction, maintenance, disease severity, and responsiveness to treatment. Prevention using continuous positive airway pressure (CPAP) is effective in some groups but is limited by its poor compliance. Thus, an improved understanding of the underlying arrhythmogenic mechanisms will facilitate the development of novel therapies and/or better selection of those currently available to complement CPAP in alleviating the burden of AF in OSA. Arrhythmogenesis in OSA is a multifactorial process characterised by a combination of acute atrial stimulation on a background of chronic electrical, structural, and autonomic remodelling. Chronic intermittent hypoxia (CIH), a key feature of OSA, is associated with long-term adaptive changes in myocyte ion channel currents, sensitising the atria to episodic bursts of autonomic reflex activity. CIH is also a potent driver of inflammatory and hypoxic stress, leading to fibrosis, connexin downregulation, and conduction slowing. Atrial stretch is brought about by negative thoracic pressure (NTP) swings during apnoea, promoting further chronic structural remodelling, as well as acutely dysregulating calcium handling and electrical function. Here, we provide an up-to-date review of these topical mechanistic insights and their roles in arrhythmia.

Keywords: atrial fibrillation; autonomic nervous system; chronic intermittent hypoxia; obstructive sleep apnoea.

Figure 1

An overview of arrhythmogenic mechanisms in obstructive sleep apnoea. Chronic intermittent hypoxia secondary to intermittent airway obstruction promotes atrial structural remodelling through local and systemic inflammation as well as by mediating oxidative stress. Peripheral chemosensing activates sympathetic reflex activity to the heart, predisposing to ectopic activity and bringing about chronic alterations in cardiomyocyte ion channel expression. Negative thoracic pressure swings experienced during apnoea promote further structural remodelling and ectopic activity through atrial stretch. Baroreceptor activation causes acute AERP shortening, predisposing to re-entry. Abbreviations: ROS: reactive oxygen species; CB: carotid body; HIF: hypoxia-inducible factor; IL: interleukin; TNF-α: tumour necrosis factor-α.