Tumor necrosis factor (TNF) is an immunomodulatory cytokine that plays an important role in many inflammatory and autoimmune diseases. We investigated the correlation between single-nucleotide polymorphisms of the TNF gene [i.e., TNF-α (−308), TNF-α (−857), TNF-α (−863), TNF-α (−1031), and TNF-β (+252)] and dilated cardiomyopathy (DCM). A total of 110 DCM patients and 110 control subjects were genotyped using polymerase chain reaction–restriction fragment length polymorphism and DNA-sequencing assay. GA/AA genotypes of TNF-α (−308) were significantly associated with increased risk of DCM compared with GG genotype (odds ratio [OR] = 1.92; 95% confidence intervals [CI], 1.05–3.52). Similarly, GA/AA of TNF-β (+252) was significantly associated with increased risk of DCM compared with GG genotype (OR = 1.97; 95% CI, 1.14–3.38). Additionally, A allele of TNF-α (−308) and TNF-β (+252) was associated with a 1.76-fold increased risk of DCM compared with G allele (OR = 1.76; 95% CI, 1.05–2.95 and OR = 1.79; 95% CI, 1.22–2.63, respectively). However, no association between DCM and TNF-α (−857), TNF-α (−1031), and TNF-α (−863) was observed. TNF gene polymorphisms may be associated with risk of DCM.

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.

Objectives: To evaluate the impact of autoantibodies against the M2-muscarinic receptor (anti-M2-R) on the clinical outcomes of patients receiving the standard treatment for peripartum cardiomyopathy (PPCM). Methods: A total of 107 PPCM patients who received standard heart failure (HF) treatment between January 1998 and June 2020 were enrolled in this study. According to anti-M2-R reactivity, they were classified into negative (n = 59) and positive (n = 48) groups, denoted as the anti-M2-R (−) and anti-M2-R (+) groups. Echocardiography, 6-min walk distance, serum digoxin concentration (SDC), and routine laboratory tests were performed regularly for 2 years. The all-cause mortality, cardiovascular mortality, and rehospitalisation rate for HF were compared between the two groups. Results: A total of 103 patients were included in the final data analysis, with 46 in the anti-M2-R (+) group and 57 in the anti-M2-R (−) group. Heart rate was lower in the anti-M2-R (+) group than in the anti-M2-R (−) group at the baseline (102.7 ± 6.1 bpm vs. 96.0 ± 6.4 bpm, p < 0.001). The initial SDC was higher in the anti-M2-R (+) group than in the anti-M2-R (−) group with the same dosage of digoxin (1.25 ± 0.45 vs. 0.78 ± 0.24 ng/mL, p < 0.001). The dosages of metoprolol and digoxin were higher in the anti-M2-R (−) patients than in the anti-M2-R (+) patients (38.8 ± 4.6 mg b.i.d. vs. 27.8 ± 5.3 mg b.i.d., p < 0.0001, respectively, for metoprolol; 0.12 ± 0.02 mg/day vs. 0.08 ± 0.04 mg/day, p < 0.0001, respectively, for digoxin). Furthermore, there was a greater improvement in cardiac function in the anti-M2-R (−) patients than in the anti-M2-R (+) patients. Multivariate analysis identified negativity for anti-M2-R as the independent predictor for the improvement of cardiac function. Rehospitalisation for HF was lower in the anti-M2-R (−) group, but all-cause mortality and cardiovascular mortality were the same. Conclusions: There were no differences in all-cause mortality or cardiovascular mortality between the two groups. Rehospitalisation rate for HF decreased in the anti-M2-R (−) group. This difference may be related to the regulation of the autonomic nervous system by anti-M2-R.