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.

Cardiac autonomic dysfunction and structural remodeling: the potential mechanism to mediate the relationship between obstructive sleep apnea and cardiac arrhythmias

“…AF and NSVT were significant risk factors for cardiovascular death and sudden cardiac death in patients with OSA ( 23 , 28 ). In multiple large prospective cohort trials, the incidence of fatal and non-fatal cardiovascular events was higher in patients with severely untreated OSA compared to patients without OSA.…”

“…Second, intrathoracic negative pressure fluctuations during inspiration against a collapsed upper airway in OSA stimulated cardiac mechanoreceptors and increased cardiac transmural pressure (a powerful stimulus to LV hypertrophy), which might mechanically stretch the myocardial walls, thereby promoting significant changes in myocardial excitability and structural remodeling of the myocardium ( 1 , 18 , 23 ). In addition, these forces also lead to a leftward displacement of the interventricular septum during diastole, which hinders LV filling and subsequently decreases stroke volume ( 12 , 24 ).…”