Review
Obstructive sleep and atrial fibrillation: Pathophysiological mechanisms and therapeutic implications

https://doi.org/10.1016/j.ijcard.2016.12.120Get rights and content

Highlights

  • Obstructive sleep apnea (OSA) is a significant risk factor for atrial fibrillation (AF).

  • Several mechanisms have been implicated in AF occurrence in OSA patients.

  • Treatment of OSA is an important component of AF management.

Abstract

Atrial fibrillation (AF) is the commonest arrhythmia in clinical practice and is associated with increased cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA), a common breathing disorder, is an independent risk factor for AF. 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. In addition, OSA has been shown to reduce success rates of antiarrhythmic drugs, electrical cardioversion and catheter ablation in AF. Effective prevention of obstructive respiratory events by continuous positive airway pressure ventilation (CPAP) reduces sympathovagal activation and recurrence of AF. The present review describes the relationship between OSA and AF, presents the pathophysiological mechanisms implicating OSA in AF occurrence, and provides an update of the potential therapeutic interventions for patients with OSA and AF.

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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