Heart rhythm | 2021
Sleep-disordered breathing is independently associated with reduced atrial connexin 43 expression.
Abstract
BACKGROUND\nPatients with atrial fibrillation (AF) exhibit decreased atrial expression of connexin (Cx), which has been causally linked to a pro-arrhythmogenic substrate. Interestingly, patients with sleep-disordered-breathing (SDB) are at increased risk for AF, but the mechanisms remain unclear.\n\n\nOBJECTIVE\nWe tested the hypothesis that patients with SDB have reduced atrial connexin expression independent of important comorbidities.\n\n\nMETHODS\nWe 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 mRNA were quantified using real-time qPCR and Western blot (Cx43). Structural atrial remodeling was investigated histologically and by qPCR. Postoperative AF was assessed by 12-lead ECG.\n\n\nRESULTS\nPatients were stratified according to apnea-hypopnea-index (SDB if AHIā„15/h, 32 vs. 45). Patients with SDB had significantly lower atrial Cx43 expression, which was negatively correlated with AHI 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, gender, diabetes, and HFrEF, (odds ratio, OR, and confidence interval, CI: 7.58 (1.891-30.375), p=0.004). Moreover, the reduced atrial Cx43 expression was strongly associated with the occurrence of postoperative AF (OR 15.749 with CI 1.072-231.472, p=0.044).\n\n\nCONCLUSION\nPatients 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.