Impact of autoantibodies against the M2-muscarinic acetylcholine receptor on clinical outcomes in peripartum cardiomyopathy patients with standard treatment

BMC Cardiovasc Disord. 2021 Dec 28;21(1):619. doi: 10.1186/s12872-021-02414-7.

Abstract

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.

Keywords: Anti-M2-muscarinic receptor; Peripartum cardiomyopathy; Vagus nerve system.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Autoimmunity
  • Autonomic Nervous System / drug effects*
  • Autonomic Nervous System / physiopathology
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / immunology
  • Cardiomyopathies / mortality
  • Cardiomyopathies / physiopathology
  • Cardiovascular Agents / therapeutic use*
  • Female
  • Heart / innervation*
  • Humans
  • Patient Readmission
  • Peripartum Period
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / drug therapy*
  • Pregnancy Complications, Cardiovascular / immunology
  • Pregnancy Complications, Cardiovascular / mortality
  • Pregnancy Complications, Cardiovascular / physiopathology
  • Prospective Studies
  • Puerperal Disorders / drug therapy*
  • Puerperal Disorders / immunology
  • Puerperal Disorders / mortality
  • Puerperal Disorders / physiopathology
  • Receptor, Muscarinic M2 / immunology*
  • Recovery of Function
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Ventricular Function, Left / drug effects

Substances

  • Autoantibodies
  • CHRM2 protein, human
  • Cardiovascular Agents
  • Receptor, Muscarinic M2