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

Background: 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: 86 PPCM patients were separated into anti-M2-R negative or positive group according to the anti-M2-R reactivity. All the patients received digoxin additional to standard treatment regimen. Echocardiography was performed at baseline and after 5 years treatment. Serum digoxin concentration (SDC) were performed every 3 to 6 months. All-cause mortality, cardiovascular mortality and re-hospitalization for heart failure were compared after 5 years of follow-up.Results: There were 82 patients completed the final data analysis, including 38 in the anti-M2-R (+) group and 44 in the anti-M2-R (-) group. The heart rate of the positive group was higher than that of the negative group at baseline (102.3 ± 6.3 vs. 95.9 ± 6.8, 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 dose of digoxin (1.21 ± 0.41 vs. 0.73 ± 0.16 ng/mL, p < 0.001). Patients in the anti-M2-R (-) group had better tolerance to metoprolol and digoxin (p < 0.05). All the PPCM patients showed prominent improvement in cardiac function, especially in the anti-M2-R (-) group. Re-hospitalization for heart failure was decreased in the negative group, but not of all-cause or cardiovascular mortality. Conclusions: Patients negative for anti-M2-R showed better tolerance to metoprolol and digoxin. Anti-M2-R maybe a predictor for vagus nerve overactivation and is associated with poor response to digoxin treatment in PPCM patients.

Serum digoxin concentrations and clinical signs and symptoms of digoxin toxicity in the paediatric population

BackgroundSerum digoxin levels have limited utility for determining digoxin toxicity in adults. Paediatric data assessing the utility of monitoring serum digoxin concentration are scarce. We sought to determine whether serum digoxin concentrations are associated with signs and symptoms of digoxin toxicity in children.MethodsWe carried out a retrospective review of patients <19 years of age who received digoxin and had serum digoxin concentrations assessed between January, 2007 and June, 2013. Data collection included patient demographics, digoxin indication, serum digoxin concentrations, signs and symptoms of digoxin toxicity, electrocardiograms, and co-morbidities. Reviewers performing chart review and electrocardiogram analysis were blinded to digoxin levels. Descriptive statistical methods were used and comparisons were made between patients with and without toxic serum digoxin concentrations (>2 ng/ml).ResultsThere were 87 patients who met study criteria (male 46%, mean age 8.4 years). CHD was present in 67.8% and electrocardiograms were performed in 72.4% of the patients. The most common indication for digoxin toxicity was heart failure symptoms (61.5%). Toxic serum digoxin concentrations were present in 6.9% of patients (mean 2.6 ng/ml). Symptoms associated with digoxin toxicity occurred in 48.4%, with nausea/vomiting as the most common symptom (36.4%), followed by tachycardia (29.5%). Compared with those without toxic serum digoxin concentrations, significantly more patients with toxic serum digoxin concentrations were female (p=0.02). The presence of electrocardiogram abnormalities and/or signs and symptoms of digoxin toxicity was not significantly different between patients with and without serum digoxin concentrations (p>0.05).ConclusionSerum digoxin concentrations in children are not strongly associated with signs and symptoms of digoxin toxicity.