Abstract
Objectives To investigate the association of serum autoantibodies against M2-muscarinic acetylcholine receptor (anti-M2-R) with atrial fibrosis in long-standing persistent atrial fibrillation (AF) patients. Methods Twenty-four long-standing persistent AF patients, scheduled to undergo hybrid ablation surgery, were enrolled in the study. Twenty-six patients with sinus rhythm, scheduled to undergo coronary artery bypass grafting surgery, were enrolled into the non-AF group. We detected serum anti-M2-R levels. Left atrial appendages were subjected to histological and molecular biological assays. Patients in the AF group received follow-up for two years. Results The AF group showed significantly higher serum anti-M2-R levels compared to the non-AF group (496.2 ± 232.5 vs. 86.3 ± 25.7 pmol/L, p < 0.001). The AF group exhibited severe fibrosis in the left atrial appendages, as indicated by increased collagen volume fraction (45.2 ± 4.7% vs. 27.6 ± 8.3%, p < 0.001), and higher levels of collagen I (0.52 ± 0.04 vs. 0.24 ± 0.06, p < 0.001) and collagen III (0.51 ± 0.07 vs. 0.36 ± 0.09, p < 0.001). TGF-β1 and CTGF were also upregulated in the AF group. A positive correlation between serum anti-M2-R levels and fibrosis of the left atrial appendage and fibrogenic indexes was observed. Conclusions Serum anti-M2-R levels are higher in AF patients and are associated with the severity of atrial fibrosis. In addition, serum anti-M2-R levels are positively correlated to TGF-β1 and CTGF expression in the left atrial appendage.
Highlights
Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting. e estimated number of AF patients worldwide in 2010 was 33.5 million, which included 20.9 million males and 12.6 million females [1]. e incidence and prevalence rates of AF are generally higher in developed countries
Comorbidities were similar between the AF and the non-AF groups. ere were no significant differences in pulmonary function and echocardiographic data, including left ventricular enddiastolic dimension and left ventricular ejection fraction among the three groups. e mean left atrium diameter of the AF group estimated by echocardiography was significantly larger than that in the non-AF group (58.0 ± 5.3 mm vs. 36.3 ± 1.1 mm; p < 0.001)
Our results further revealed a positive correlation between serum antiM2-R levels and TGF-β1 and Cardiology Research and Practice tissue growth factor (CTGF) expression in left atrial appendage (LAA) tissues. ese findings suggest that serum anti-M2-R plays an important role in fibrosis-associated AF and its potential mechanism
Summary
Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting. e estimated number of AF patients worldwide in 2010 was 33.5 million, which included 20.9 million males and 12.6 million females [1]. e incidence and prevalence rates of AF are generally higher in developed countries. E incidence and prevalence rates of AF are generally higher in developed countries. 25% of middle-aged adults in Europe and the USA are predicted to develop AF, with higher prevalence in older people and in patients with hypertension, diabetes mellitus, coronary artery disease, or heart failure [2,3,4]. Circulating autoantibodies against M2-muscarinic acetylcholine receptors (anti-M2-R) have been found in several cardiac arrhythmias [7]. Our previous study showed that serum anti-M2-R levels are higher in AF patients and positive for anti-M2-R as an independent predictor for the recurrence of AF one year after radiofrequency catheter ablation [8]. A recent report has shown that serum anti-M2-R has a predictive value for moderate-extensive left atrial fibrosis defined by delayed-enhancement magnetic resonance imaging (DE-MRI) in patients following cryoablation [9].
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