Sleep-disordered breathing is independently associated with reduced atrial connexin 43 expression

Abstract

Background: Patients with atrial fibrillation (AF) exhibit decreased atrial expression of connexin (Cx), which has been causally linked to a proarrhythmogenic substrate. Interestingly, patients with sleep-disordered breathing (SDB) are at increased risk of AF, but the mechanisms remain unclear.

Objective: We tested the hypothesis that patients with SDB have reduced atrial Cx expression independent of important comorbidities.

Methods: We analyzed right atrial appendage biopsies from 77 patients undergoing coronary artery bypass grafting. Patients were tested for SDB by polygraphy before surgery. Expression of Cx40 and Cx43 messenger RNA was quantified using real-time quantitative polymerase chain reaction and Western blot (Cx43). Structural atrial remodeling was investigated histologically and by quantitative polymerase chain reaction. Postoperative AF was assessed by 12-lead electrocardiography.

Results: Patients were stratified according to apnea-hypopnea index (SDB if apnea-hypopnea index ≥15 per hour, n = 32 vs n = 45). Patients with SDB had significantly lower atrial Cx43 expression, which was negatively correlated with apnea-hypopnea index and oxygen desaturation index. No significant increase in atrial fibrosis or expression of hypertrophy and inflammatory markers was observed. Interestingly, SDB remained the strongest independent predictor of decreased atrial Cx43 expression in a multivariate logistic regression model including age, sex, diabetes, and heart failure with reduced ejection fraction (odds ratio 7.58; 95% confidence interval 1.891-30.375; P = .004). Moreover, reduced atrial Cx43 expression was strongly associated with the occurrence of postoperative AF (odds ratio 15.749; 95% confidence interval 1.072-231.472; P = .044).

Conclusion: Patients with SDB exhibited decreased atrial Cx43 expression, which correlated with the severity of SDB. This correlation was independent of several concomitant diseases and may be linked to an increased risk of AF after cardiac surgery.

Trial registration: ClinicalTrials.gov NCT02877745.

Keywords: Atrial conduction; Atrial connexin expression; Atrial fibrillation; Connexin 43; Sleep apnea.