During inhalation, obstruction of the upper airways leads to an increase in intrathoracic pressure. This heightened pressure not only worsens airway collapse and obstruction but also exerts greater force on both the atrial and ventricular walls (37). The resultant increased tension on the atrial walls accelerates the chronic progression of atrial dilation, with this dilated atrium subsequently initiating the onset of AF (37). Atria that are acutely dilated are susceptible to inducing a variety of atrial arrhythmias (38). It should be noted that this is one hypothesis and that other mechanisms may also be involved.

In patients with OSA, rapid alterations in cardiac autonomic balance occur, varying with the different stages of acute apneic episodes. Typically, during apnea, there is an overactivation of the parasympathetic nervous system, manifesting as arrhythmias primarily characterized by bradycardia and conduction blocks. Conversely, during the resumption of breathing, there is a rebound excitation of the sympathetic nervous system, with heart rate normalizing or becoming tachycardic (32). Yu et al. reported that OSA notably elevates the inducibility of AF and augments left renal sympathetic nerve activity; however, these activities can be inhibited through low-level tragus vagal stimulation (15). Xiaokereti et al., utilizing a dog model, demonstrated that OSA significantly enhances neural remodeling in both the left stellate ganglion and left atrium. Excessive activity of the left stellate ganglion may expedite left atrial neural remodeling, thus augmenting AF inducibility (39). Linz et al., employing a pig model, indicated that negative tracheal pressure during obstructive events is a potent trigger for AF. Negative tracheal pressure primarily leads to a shortening of the atrial effective refractory period and increases vulnerability to AF by activating the vagus nerve (40). Furthermore, hyperactivity of the sympathetic nervous system can accelerate atrial fibrosis via activation of the renin-angiotensin-aldosterone system. Goette et al. found that, compared to sinus rhythm, the expression of angiotensin-converting enzyme during persistent AF is elevated threefold (41).

OSA, resulting from either complete or incomplete ventilation restriction, leads to the development of CIH within the body. A multitude of studies have provided evidence that CIH plays a mediating role in atrial structural remodeling, thereby exerting detrimental effects on the inducibility of AF (42–48). In an OSA model established by Ramos et al., histological analysis revealed a 43% increase in the interstitial collagen fraction in the atria of OSA rats compared to the control group, while no such difference was observed in the ventricles (44). Linz also employed a rat model, subjecting the rats to intermittent negative airway pressure (12 times per hour) to simulate mild to moderate OSA, with rats not exposed to intermittent negative airway pressure serving as the control group (CTR). The study found that acute intermittent negative airway pressure increased susceptibility to atrial oxidative stress. In the chronic test series, although atrial oxidative stress did not accumulate, histological analysis of the atria revealed an increase in cardiomyocyte diameter, a decrease in connexin 43 (CX43) expression, and an increase in interstitial fibrosis formation (43).

Yang et al. conducted a study where 60 male Sprague-Dawley rats were randomly divided into four groups: control group, CSD (cardiac sympathetic denervation) group, CIH group, and CIH + CSD group. They analyzed cardiac structure using HE staining and echocardiography, detected CX43 and tyrosine hydroxylase using Western blot, immunohistochemistry, and immunofluorescence, and recorded blood pressure, blood gas, heart rate, etc. The study demonstrated that CIH induces atrial remodeling, increases AF inducibility, leads to excessive sympathetic innervation, and decreases CX43 expression (46). Four years later, Yang et al. further conducted in vivo experiments using OSA rats and in vitro experiments using the CIH H9c2 cell model to investigate the role and potential mechanisms of Cx43 in OSA-related AF. The study revealed that Cx43 overexpression inhibits the expression of calcium/calmodulin-dependent protein CaMKII.γ through the Cx43/CaMKIIγ/HIF-1 axis, ultimately reducing myocardial apoptosis and the incidence of AF (45). Bober et al. focused on examining the effects of CIH on atrial electrophysiology and arrhythmia susceptibility. The study found that CIH increases susceptibility to atrial arrhythmia induction, primarily due to parasympathetic activation. The enhanced susceptibility to AF is accompanied by increased electrophysiological responses of atrial muscle to carbachol and isoproterenol, reduced response to propranolol, and elevated atrial M2 receptor protein levels (42).

As a consequence of recurrent upper airway obstruction, hypoxemia is frequently accompanied by hypercapnia, which further exacerbates the risk of AF. Stevenson et al. developed a sheep model of hypercapnia and observed a significant prolongation of the effective refractory period by 152%, alongside an increase in conduction time relative to baseline measurements. Upon resolution of hypercapnia, the ERP promptly reverted to baseline levels; however, the recovery of conduction time was notably delayed by an average of 117 ± 24 min. This disparity in the recovery rates between ERP and conduction time may underlie the heightened susceptibility to AF witnessed during the post-hypercapnia period (49).

A growing body of evidence implicates a strong correlation between inflammation and AF. Elevated serum levels of inflammatory markers have been documented in AF patients, with expression also noted in cardiac tissue. Furthermore, anti-inflammatory drugs have demonstrated efficacy in AF animal models. Specifically, AF patients exhibit heightened circulating levels of inflammatory markers, including C-reactive protein, interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α. It is noteworthy that these marker levels are typically higher in patients with persistent AF than in those with paroxysmal AF (50). Inflammation plays a pivotal role in modulating cell signaling pathways pertinent to fibrosis, apoptosis, and hypertrophy, which can facilitate structural remodeling of the atrium and augment the propensity for AF induction (51, 52).

Cellular bioelectricity arises from the movement of charged ions through cell membranes, facilitated by ion channels. In individuals with AF, electrical remodeling takes place within the atrium, encompassing alterations in various ion channels (47, 53). Zhang et al. conducted a study where they randomly assigned 80 male Sprague-Dawley rats into two groups: a control group and a CIH group, with 40 rats in each. Utilizing RT-qPCR, Western blot, and immunohistochemistry techniques, they assessed the expression levels of ion channel subunits. Their findings revealed a significant reduction in the densities of INa, ICa-L, and Ito in the CIH group compared to the control (53).

Table 2 listed representative studies on the effects of CPAP on Patients with OSA and AF.

A retrospective analysis conducted by Ogbu et al. examined individuals diagnosed with unstable angina, acute myocardial infarction, acute decompensated heart failure, and AF with rapid ventricular response, who concurrently had OSA, utilizing data from the National Inpatient Sample spanning 2016 to 2019. The findings revealed that, among patients with OSA, the application of CPAP led to a significant increase in both the duration of hospital stay (with an adjusted mean difference of 1.49 days) and hospital expenses (adjusted mean difference of $1,168). The routine administration of CPAP during acute cardiovascular episodes may potentially attenuate or nullify the beneficial adaptive responses elicited by chronic, intermittent ischemic stress (71). In a randomized controlled trial, Traaen et al. enrolled 108 participants with paroxysmal AF and moderate-to-severe OSA to evaluate the differences in AF burden (defined as the percentage of time spent in AF) between those who received CPAP in addition to standard care and those who received only standard care. The results indicated that, over the final 3 months of CPAP intervention, the mean time spent in AF decreased from 5.6% at baseline to 4.1% in the CPAP group, and from 5.0 to 4.3% in the control group. Traaen et al. concluded that CPAP therapy did not yield a statistically significant reduction in AF burden among patients with paroxysmal AF and OSA (26). Hunt et al. conducted another randomized controlled trial, where 37 patients were randomly assigned to the CPAP treatment group and 46 to the standard treatment group. Within 3–12 months following PVI, 57% of patients in both groups experienced at least one AF occurrence. The AF burden decreased after ablation in both groups, with no significant difference between them. The study’s conclusion was that CPAP treatment did not further diminish the risk of AF recurrence post-ablation (25). Caples et al. carried out the inaugural randomized controlled trial to explore the effect of OSA treatment on AF recurrence after direct current cardioversion. No significant difference was observed between patients who received CPAP treatment and those who received usual care. AF was reported in 25% of patients in both the CPAP and control groups, with durations of 129.0 ± 166.5 days and 109.3 ± 73.2 days, respectively. At follow-up, there were no notable differences in the Epworth Sleepiness Scale or the Functional Outcomes of Sleep Questionnaire (24). Srivali et al. performed a single-center retrospective study at a tertiary referral center, which included 30,188 patients with obstructive and central sleep apnea. Following the intervention, no significant difference was found in the time to AF recurrence between CPAP adherent users and non-users. The study’s findings indicated that CPAP treatment did not influence the time to AF recurrence after intervention (72).

The existing evidence shows divergent results regarding the effectiveness of CPAP treatment effectiveness in preventing the onset or recurrence of AF. Many studies have explored how CPAP can improve atrial remodeling or some electrocardiophysiological surrogate endpoints in patients with OSA. Some clinical studies have demonstrated that CPAP can reduce the incidence of AF in OSA patients. However, there is a lack of evidence regarding whether CPAP can delay the progression of AF to a persistent state. Furthermore, the impact of CPAP on AF incidence may also depend on the characteristics of the population, as its effects in the general OSA population may differ from those in patients who have undergone AF cardioversion (i.e., recurrence rates).

Additionally, the differences between the mixed apnea group and the obstructive apnea group need to be taken into account. The mixed apnea group, which often exhibits a high degree of respiratory instability, may not be directly comparable to the group primarily exhibiting obstructive apnea. Moreover, CPAP therapy is often less effective in patients with mixed apnea. When comparing outcomes across these groups, improvements in sleep-disordered breathing or atrial remodeling after CPAP therapy should be considered. These points require further exploration through more research in the future.

Many clinical studies, despite having a control group, only make comparisons to baseline and not to the control group in their results section. Furthermore, due to the relatively small number of patients enrolled, the statistical power of these studies may be affected, leading to inconsistent research conclusions at present. Larger randomized controlled trials are needed in the future to clarify the effect of CPAP on patients with AF.

There is considerable variation in the design of experiments across studies. For example, Fein et al.’s investigation enrolled a prospective cohort of consecutive OSA and symptomatic AF patients who were referred for AF ablation surgery from July 2007 to January 2010. Conversely, Srivali et al. examined all OSA patients who underwent polysomnography between January 1992 and December 2014 and subsequently received AF interventions (ablation or cardioversion). These retrospective analyses may be susceptible to selection bias.

The average nightly usage of CPAP significantly affects the prognosis of OSA patients and potentially influences the outcomes of OSA-related AF as well. Ensuring adequate therapy duration and monitoring adherence is crucial for ensuring that CPAP is effective.

The follow-up periods for assessing AF recurrence vary widely among studies, spanning from 2 to 12 months. This inconsistency cannot exclude the possibility that longer or shorter follow-up intervals might alter the observed AF recurrence rates.

Based on the current literature, the following are the key areas that future research should prioritize:

Current research exploring the impact of CPAP on AF in OSA patients primarily consists of clinical studies, with limited use of animal models. To gain a deeper understanding of the mechanisms and effects of CPAP in this context, future studies should establish more animal models to investigate the impact of CPAP on OSA-related AF.

Inadequate adherence to CPAP therapy poses a significant challenge to effective OSA management. The reasons for non-adherence are multifaceted, encompassing social, psychological, and medical factors (73). Strategies to improve CPAP adherence may include comprehensive communication with patients and their families, the utilization of Automatic Positive Airway Pressure devices, and early administration of sedative-hypnotic medications, among other approaches. More importantly, future research needs to focus on establishing precise patient selection criteria to more accurately evaluate the effectiveness of CPAP in preventing or mitigating the onset of AF

Beyond CPAP, several alternative treatment options exist for OSA, including lifestyle modifications, oral appliances, neuromuscular electrical stimulation, and surgical interventions. OSA patients urgently require more novel therapeutic strategies (74). Recent studies have shown that the combined use of anticholinergic drugs and norepinephrine agonists, such as AD109 (atomoxetine + aroxybutynin), can improve OSA. The mechanism underlying this combination therapy likely involves stimulating the upper airway dilator muscles and enhancing genioglossus responsiveness, thereby reducing sleep apnea episodes (75, 76).