Contribution of Sleep Apnea to AF, its Impact on Outcome of AF Ablation, and the Role of CPAP Therapy

The association between obstructive sleep apnea (OSA) and atrial fibrillation (AF) is well established. Approximately half of patients with AF have OSA, and the proportion of patients with OSA is higher in patients with frequent paroxysmal or persistent AF than in those with low frequency paroxysmal AF. ¹ Furthermore, patients with OSA have a significantly higher risk of developing AF, with a reported incidence of 10-30%.^2,3 This risk in patients with OSA to develop AF is impacted by the severity of the disease, as patients with mild OSA carry a two-fold increased risk to develop AF compared with a five-fold increased risk in patients with moderate or severe OSA.⁴ While these two disorders share risk factors and comorbidities including male gender, hypertension, coronary artery disease, and heart failure, OSA appears to be an independent risk factor for development of AF.⁵

OSA is estimated to affect ~10% of adult individuals, a figure that has been increasing due to the aging population and the obesity pandemic, both of which contribute to the OSA risk. In addition, diagnostic technology has become more accessible, also utilizing home sleep testing devices, such that earlier prevalence of OSA was likely underestimated. Furthermore, the prevalence in patients with cardiovascular disease is likely considerably higher than 10%, and is currently estimated at 50-80%.⁶ 

OSA is defined by repetitive collapse of the pharyngeal airway during sleep, resulting in fluctuations in intrathoracic pressure, hypoxemia, hypercapnia, and catecholamine surge. Hypoxemia and hypercapnia generate pulmonary artery vasoconstriction, leading to right heart strain. In addition to autonomic abnormalities, inflammatory pathways have been implicated in OSA, perhaps as a result of hypoxemia and obesity.⁷ While autonomic imbalance and inflammation can act as triggers for AF in patients with OSA, recent data suggests that OSA also leads to atrial substrate changes via induction of cardiac remodeling pathways, resulting in atrial fibrosis and conduction slowing — a milieu for reentrant arrhythmias including atrial fibrillation. Thus, acute obstructive sleep apnea episodes lead to left atrial dilatation stretch and development of an underlying substrate for AF. Further acute episodes of apnea lead to autonomic imbalance that can trigger AF from PV and non-PV triggers. 

From a therapeutic standpoint, patients with OSA are more resistive to rhythm control strategies and are less likely to maintain sinus rhythm after initiation of antiarrhythmic drug therapy, electrical cardioversion, or AF ablation procedures.^8-10 Importantly, recent data suggests that treatment of sleep apnea may have a favorable impact on arrhythmia control in these patients with sleep apnea. 

We have recently shown that treatment of OSA with continuous positive airway pressure (CPAP) ventilation significantly reduced the rate of arrhythmia recurrence after AF ablation procedures when compared to a matched group of patients with untreated OSA (Figure 1). In fact, CPAP therapy resulted in improved arrhythmia-free survival that was similar to patients without OSA at all. Conversely, we found that patients with untreated OSA that underwent an AF ablation procedure had an increased risk of arrhythmia recurrence that was similar to patients with OSA that did not undergo ablation. This favorable effect of CPAP therapy on arrhythmia control in patients with OSA has been further reported in another recent study.¹¹ 

The mechanism by which CPAP therapy reduces the risk of AF recurrence after AF ablation is not entirely clear. CPAP, by preventing episodes of inspiratory effort against a closed glottis and increased negative intrathoracic pressure, may reduce left atrial dilatation, stretch and structural remodeling. However, the beneficial effect of CPAP extends also to patients with pre-existing left atrial scar, suggesting that CPAP therapy may reduce AF occurrence via other mechanisms. Hypoxemia leads to catecholamine surge and shortening in atrial effective refractory, promoting ectopic atrial and pulmonary vein activity. Thus, CPAP therapy, by preventing hypoxemia, may reduce triggered atrial activity and AF. CPAP therapy also reduces inflammation and oxidative stress, both of which have been reported to promote AF.¹² Taken together, CPAP therapy reduces the recurrence of AF in patients with OSA by a myriad of effects including structural, electrical and pleiotropic. This exciting data highlights the importance of shifting our traditional approach from treating an arrhythmia only to treating patients with arrhythmia, patients that may have modifiable comorbidities contributing to AF. 

Although the prevalence of OSA in cohorts of patients with AF is nearly 50%, in the “real-world” practice, this prevalence appears to be significantly smaller, ranging from 10-20%. This discrepancy is likely explained by low clinical suspicion and underdiagnosis of sleep apnea in patients with AF, as many of these patients do not exhibit traditional symptoms of snoring and daytime fatigue. In addition, clinical questionnaires for the diagnosis of OSA are not part of the routine care for AF. However, as the prevalence of sleep apnea in patients with AF is at least moderate and treatment of this condition has significant implications for arrhythmia control, it is reasonable to screen all patients with AF for a concomitant sleep disorder. Initiation of CPAP therapy should be considered part of a multidisciplinary approach for the treatment of patients with AF. In addition, treatment of sleep apnea has further implications beyond arrhythmia control that include reduction in blood pressure, risk for stroke, and improvement in the overall well-being. 

We have started a single-center prospective study aimed to: 1) evaluate the prevalence of OSA in patients with symptomatic AF; 2) examine the patient and institutional feasibility of screening all patients with symptomatic AF for OSA; and 3) examine the compliance and effect of CPAP therapy on arrhythmia control.¹³ With the increasing availability of home sleep study devices that are sensitive, specific, and easy to use, the challenge to universally screen all patients with AF may be more feasible than ever. Whether this approach can reduce AF burden and lead to better patient care remains to be discovered. 

Summary 

The presence of OSA with its associated atrial structural and electrical remodeling not only potentiates the risk of developing atrial fibrillation, but also limits the success of rhythm control strategies including ablation. CPAP therapy may help mitigate these effects, and improve the outcomes of ablation in the OSA patient population. The higher rates of recurrent AF following ablation seen in patients with OSA not using CPAP emphasizes the importance of appropriate patient selection, continuous compliance with CPAP therapy, and highlights an avenue to further improve long-term success of the ablation. Careful attention should be paid to screening patients with AF for OSA, especially prior to undergoing ablation. 

Disclosures: The author has no conflicts of interest to report regarding the content herein.   

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