The Effect of Autoantibody against M2-Muscarinic Acetylcholine Receptor in Heart Failure Patients on Digoxin Treatment

Abstract

Background: Autoantibody against M2-muscarinic acetylcholine receptor (anti-M2AChR) has a biological effect similar to a vagus agonist. Digoxin has a function of vagus nervous system stimulation. We hypothesized that anti-M2AChR is highly correlated with digoxin in patients with chronic heart failure (CHF). Methods: Synthetic M2AChR peptides served as the target antigen in an ELISA were used to screen the sera of 80 CHF patients, who were separated into a negative (–) or positive (+) anti-M2AChR group according to their anti-M2AChR reactivity. Echocardiography and serum digoxin concentration (SDC) were performed at baseline and after 1 year of digoxin in combination with the standard treatment regime. The end-point events were compared over 1 year of follow-up. Results: Seventy-two CHF patients completed the final data analysis, including 32 (+)anti-M2AChR and 40 (–)anti-M2AChR patients. The resting heart rate of the positive group was higher than that of the negative group at baseline (p < 0.05; 89.0 ± 1.6 vs. 83.8 ± 1.1 bpm). Both groups showed improvement in the left ventricular end-diastolic and end-systolic dimensions and ejection fraction with digoxin in combination with the standard treatment regime for 1 year (all p < 0.01). However, the 32 patients with (–)anti-M2AChR had greater improvements than the 40 patients with (+)anti-M2AChR, and this was accompanied by a marked decrease of rehospitalization (all p < 0.01) but not of cardiovascular mortality after 1 year. The SDC of patients with (–)anti-M2AChR was significantly lower than that of patients with (+)anti-M2AChR (p < 0.05; 0.63 ± 0.05 vs.1.16 ± 0.06 ng/mL) and had a positive correlation with anti-M2AChR (r = 0.81, p < 0.001). Conclusion: These results suggested that anti-M2AChR could be a useful biomarker of vagus nerve overactivation and is associated with a poor response to digoxin treatment in CHF patients.