Mechanisms underlying atrial fibrillation onset in patients with obstructive sleep apnea

Atrial fibrillation (AF) is often associated with obstructive sleep apnea (OSA). Several OSA mechanisms might lead to AF onset, including intrathoracic pressure shifts, sympatho-vagal imbalance and hypoxemia. A better understanding of the relevant pathophysiologic mechanisms might lead to better risk stratification of patients with AF and OSA, since the necessity of diagnosing and treating OSA as upstream therapy for AF remains to divide the cardiologic community. This study aimed to clarify the role of acute mechanisms of OSA in the onset of AF during sleep. This could ruther elucidate in which patient with OSA and AF, OSA is a relevant proarrhythmogenic factor and in which it is merely a bystander.

We conducted a prospective observational study with a polysomnography (PSG). A case-crossover design was employed to analyse AF onsets, comparing a 90-second hazard period preceding AF onset with control periods, matched for sleep stage, within the same patient. Control periods were selected using a backward moving window approach, starting five minutes prior to the onset of AF. We assessed heart rate variability using root mean square standard deviation (RMSSD) as a surrogate for sympatho-vagal tone, respiratory inductance plethysmography belts as surrogate for intrathoracic pressure and hypoxic burden. A linear mixed model was used to compare hazard and control periods, incorporating random effects to account for variability between patients and between hazard and control periods. We corrected for age, sex, left atrial volume and body mass index. Sensitivity analyses were performed to validate the results across extended control periods.

A total of 198 patients were eligible for participation of which 158 were referred for PSG. Forty patients declined referral to a sleep medicine clinic. Of the remaining 158 patients, 155 were diagnosed with OSA. Among the 155 patients analysed, 19 patients had 45 usable onsets of AF. Non-usable onsets were onsets <5 minutes after termination of AF or occurring during wakefulness. RMSSD was significantly higher during hazard periods compared to control periods (estimate 0.599, p = 0.003), indicating enhanced vagal tone prior to AF onset. Heart rate, relative respiratory effort, and hypoxic burden did not differ significantly between these periods. The findings were consistent in sensitivity analysis, with RMSSD remaining significant (p = 0.002).

Our study highlights that increased vagal tone, as reflected by elevated RMSSD, is a predominant mechanism in the acute onset of AF among patients with OSA. Hypoxemia and respiratory effort did not show significant variations. These results suggest that RMSSD could serve as a potential clinical marker for identifying patients who may benefit from targeted OSA treatment in rhythm control strategies for AF. Future research should aim at identifying a pro-arrhythmogenic OSA phenotype for improved patient selection.

Patient characteristics per subgroup