Effects of autoantibody against M2-muscarinic acetylcholine receptor in peripartum cardiomyopathy patients on digoxin additional to standard treatment

Objectives To evaluate the effects of autoantibodies against the M2-muscarinic receptor (anti-M2-R) on digoxin additional to standard treatment in peripartum cardiomyopathy (PPCM) patients. Methods 107 PPCM patients, receiving digoxin and standard treatment regimen for HF, were enrolled between January 1998 and June 2020, who were separated into anti-M2-R negative (n = 59) or positive (n = 48) group according to the anti-M2-R reactivity. Echocardiography and serum digoxin concentration (SDC) were performed regularly. All-cause mortality, cardiovascular mortality and re-hospitalization for heart failure were compared. Results 103 patients completed the final data analysis, including 46 in the anti-M2-R (+) group and 57 in the anti-M2-R (-) group. Heart rate of the positive group was lower than that of the negative group at baseline (102.7 ± 6.1 vs. 96.0 ± 6.4, p < 0.001). The initial SDC of patients in the positive group was higher than that of patients in the negative group with the same dosage of digoxin (1.25 ± 0.45 vs. 0.78 ± 0.24 ng/mL, p < 0.001). Anti-M2-R (-) patients had better tolerance to metoprolol (38.4 ± 4.6 mg b.i.d. vs. 27.4 ± 5.0 mg b.i.d., p < 0.0001) and digoxin (0.12 ± 0.02 mg/day vs. 0.08 ± 0.04 mg/day, p < 0.0001). The improvement of heart function was obvious in the first year, especially in the first half. Furthermore, anti-M2-R (-) patients showed better improvement than that in anti-M2-R (+) patients. Re-hospitalization for heart failure was decreased in the negative group, but not of all-cause or cardiovascular mortality. Conclusions Anti-M2-R maybe a predictor for vagus nerve overactivation and is associated with poor response to digoxin in PPCM patients.