High Dosage of Carvedilol is Effective to Induce Remodeling and Improve of Survival in Children with Dilated Cardiomyopathy

Abstract

We aim to evaluate clinical outcomes, echocardiographic changes, heart rate (HR) modifications and side effects in children with dilated cardiomyopathy (DCM) and chronic heart failure (HF) treated by high dosage of carvedilol. We prospectively enrolled pediatric patients with DCM and ventricular dysfunction (EF <45%) referred to our institute. All enrolled patients were treated with high dosage of carvedilol coupled to heart failure therapy (ace inhibitors; diuretics, aldosterone blockade) in order to achieve a reduction of heart rate > 20% from baseline. Conventional treatment should be started from at least 1 month. Initial dosage of carvedilol was 0.1 mg/kg/day, up-titrated every 2 weeks to a maximum dose of 1 mg/kg/day. All data were compared to an historical control group treated with low dose of carvedilol or without beta-blockers. Data were collected before and after one year of maximum tolerated treatment. 65 patients (58% male) were enrolled, mean age was 13.4 +/- 9 years. 72 patients (48% male) were enrolled in the control group, mean age was 3.9 +/- 3.7. Mean duration of treatment was 50 months. HR reduction and EF improvement were statistically significant after treatment (mean HR reduction was 23%, p<0,0001; mean EF improvement 11,9%, p<0,0001); as well as decrease in LV diameters (p=0.001), volumes (p=0.029) and BNP levels (p=0.029) compared to control group. All patients survived, and 4 out of 4 were delisted from transplant list; on the contrary 32 patients of group 2 were transplanted and 11 died. Blood pressure remained stable for all patients treated with carvedilol and no side effects were recorded. High dosage of carvedilol up-titrated to achieve a reduction of heart rate of 20%, in addition to standard therapy, significantly improve ventricular function and survival in pediatric patients with DCM.