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Clinical and animal studies suggest that beta1-adrenergic and M2 muscarinic receptor autoantibodies (beta1-AAbs and M2-AAbs) play important roles in the pathophysiological process of chronic heart failure (CHF). Removal of these autoantibodies improved haemodynamic parameters and left ventricular ejection fraction patients with CHF. The goal of this project is to evaluate whether beta1-AAbs and M2-AAbs predict prognosis and sudden cardiac death (SCD) in CHF.A total of 2062 patients with CHF and 824 control subjects were recruited. Beta1-AAbs and M2-AAbs were detected by the enzyme-linked immunosorbent assay (ELISA) method, and the correlation between these autoantibodies and the prognosis of CHF was analysed. During a median follow-up period of 36 months (0.40 ± 65 months), 379 (21.56%) cases died—164 had dilated cardiomyopathy (DCM) and 215 had ischaemic cardiomyopathy (ICM). Of these, SCD occurred in 69 cases (40.37%) of DCM and in 84 cases (39.07%) of ICM. Positivity for beta1-AAbs in DCM and ICM was significantly higher than for the controls (8.1% and 8.25% v.s 2.2%, both P < 0.01). However, positive M2-AAbs did not show any statistical difference between the three groups. Cox regression analysis revealed that positive beta1-AAbs were associated with higher mortality in CHF and that it predicted SCD for DCM [hazard ratio (HR) 4.51, 95% confidence interval (CI) 2.405–8.471] and ICM (HR 3.749, 95% CI 2.389–5.884) patients, but not non-SCD (NSCD) patients.The rates of positive beta1-AAbs were higher in CHF patients than in the controls. Positive beta1-AAbs might serve as an independent predictor for SCD in patients with CHF.