ReviewObstructive sleep and atrial fibrillation: Pathophysiological mechanisms and therapeutic implications
Introduction
AF is the commonest arrhythmia, occurring in 1–2% of the general population [1]. In the modern era, AF constitutes a major cardiovascular challenge, as it is associated with increased rates of death [2], [3], stroke [4] and thromboembolic events, heart failure [5] and hospitalizations. The prevalence of OSA is substantially higher among patients with AF, strongly indicating that OSA may be contributing to the initiation and perpetuation of the arrhythmia [6], [7]. The severity of OSA, as measured by nocturnal oxygen desaturations, has been found to correlate to the prevalence of AF [8]. Several pathophysiological mechanisms, including apnea-induced hypoxia, intrathoracic pressure shifts, sympathovagal imbalance, atrial remodeling, oxidative stress, inflammation and neurohumoral activation have been implicated in the occurrence of AF in OSA patients [9]. The relationship between OSA and AF might be even more relevant considering the role of obesity as a common mediating epidemiological and causal link [10]. This review presents the association between OSA and AF, describes the pathophysiological mechanisms implicated in AF occurrence in OSA patients and highlights the emerging therapeutic interventions for patients with OSA and AF.
Section snippets
Obstructive sleep apnea: definition and diagnosis
Obstructive sleep apnea is characterized by recurrent episodes of partial or complete upper airway collapse during sleep, that is highlighted by a reduction in - or complete cessation of - airflow despite documented ongoing inspiratory efforts [11]. A hypopneic episode should meet one of the following criteria: i) > 50% reduction in airflow or tidal volume for at least 10 s ii) moderate reduction in airflow (< 50%) with arterial oxygen desaturation > 3%, or iii) moderate reduction in airflow with
Obstructive sleep apnea as a risk factor for atrial fibrillation
Several studies have confirmed the increased incident of AF in OSA patients (Table 1) [6], [8], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26]. The Sleep Heart Study demonstrated that the risk of AF is 4 times bigger in patients with sleep disordered breathing (obstructive and central sleep apnea) compared to patients with no sleep-disordered breathing [14]. Gami et al. showed that for patients with OSA under age 65, the hazard ratio of developing any type of
Changes in blood gases
OSA induces repeated episodes of hypoxia that trigger chemoreflex and enhance sympathetic nerve activity, leading to tachycardia and blood pressure elevation, especially at the end of the apnoeic episodes [29]. Tachycardia and HT increase myocardial oxygen demand while myocardial oxygen supply is at its lowest level due to hypoxia. This results in repeated myocardial and subsequently atrial ischemia during sleep, thereby promoting AF. Atrial myocardial perfusion abnormalities and coronary flow
Oxidative stress, inflammation and neurohumoral activation
Hypoxia and reoxygenation cycles in OSA cause a change in oxidative balance, leading to the formation of reactive oxygen species capable of reacting with other organic molecules impairing their functions [69]. Thioredoxin, malondialdehyde, superoxide dysmutase, and reduced iron are commonly used biomarkers and show a more consistent relationship between increased oxidative stress and OSA [69]. Noteworthy, reduced polysomnography total sleep time is associated with elevated myeloperoxidase
Continuous positive airway pressure
The gold standard for OSA therapy is CPAP [84]. The positive pressure keeps the pharyngeal area from collapsing and thus helps alleviate the airway obstruction [84]. Muscle sympathetic nerve activity is greatly elevated in patients with OSA during normoxic daytime wakefulness. Continual CPAP treatment seems to be an effective long-term treatment for elevated muscle sympathetic nerve activity likely due to its effects on restoring brainstem structure and function [85], [86]. Baroreflex
Treatment of obstructive sleep apnea reduces thromboembolic risk in atrial fibrillation
OSA is directly and independently associated with elevated thromboembolic risk in AF. OSA patients have higher CHADS2 and CHA2DS2-VASc scores than patients without sleep disordered breathing [124]. Also, mean CHADS2 and CHA2DS2-VASc scores rise with OSA severity and the differences in the stroke risk are significant even across different age strata, and the trend for point values in CHADS2 and CHA2DS2-VASc scores rises along with OSA severity according to AHI [124]. Yaranov et al. reported that
Conclusion
OSA represents a well-established, but possibly overlooked risk factor for AF. Several pathophysiological mechanisms seem to be implicated in AF occurrence and negatively affect the efficacy of pharmacological and ablative therapy for AF in OSA. CPAP therapy reduces sympathovagal activation and has been shown to decrease the risk of transition from paroxysmal to persistent AF, as well as arrhythmia recurrence. The existing evidence base advocates for screening and treatment of OSA in cases of
Conflict of interest statement
No conflicts of interest to declare.
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2024, The Lancet Regional Health - EuropeEffect of continuous positive airway pressure therapy on recurrence of atrial fibrillation after pulmonary vein isolation in patients with obstructive sleep apnea: A randomized controlled trial
2022, Heart RhythmCitation Excerpt :AF and obstructive sleep apnea (OSA) frequently coexist, and the presence and severity of OSA are independently associated with the burden of AF.3 It has been suggested that treatment of OSA with continuous positive airway pressure (CPAP) may reduce the frequency and duration of AF.4,5 Furthermore, observational studies have shown increased prevalence of AF in patients with OSA and reduced recurrence with CPAP use.6,7