Thirty-five Patients treated with AAD and 14 randomly selected patients without AAD (control group), evaluated by consecutive Holter recordings, were included. The 35 patients treated with AAD had 46 medication episodes, with a maximum of 3 episodes per child. In total, flecainide was prescribed 10 times, beta-blockers 18 times, sotalol 7 times, and verapamil 11 times. Children who received more than one type of anti-arrhythmic drugs during different medication episodes are represented in more than one group. The 14 randomly selected untreated patients had 20 episodes with consecutive Holter recordings. The baseline characteristics of the treated groups (before the start of medication) and control group were comparable regarding age at diagnosis, sex, weight, PVC burden, QRS morphology, coupling interval, and LV function (Table 1). The untreated group, as expected, had less symptoms, less VTs, and a lower LVEDD Z-score as compared to the treated groups. Symptoms in both the treated groups and the control group varied widely, consisting of palpitations, dizziness, fatigue, chest pain or syncope. The dosage of the medication prescribed was based on bodyweight and the way of administration depended on the patients age and available dosage form (i.e., multiple dosages per day or slow-release tablets). Therefore, the mean medication dose in mg per kg bodyweight per day is presented in Table 2.
The mean interval between Holter recordings was significantly different between the five groups (p = 0,015), with the control group having the longest mean interval of 427 days (SD 310), the flecainide group 247 days (SD 253), the beta-blocker group 139 days (SD 175), the sotalol group 261 days (SD 435), and the verapamil group 145 days (SD 160).
The mean follow-up time in our study was 3.8 years, with no statistically significant differences between the five groups (p = 0.924): 4.2 years for the control group (SD 3.6), 3.4 years (SD 1.8) for children in the flecainide group, 3.4 years (SD 3.2) in the beta-blocker group, 4.0 years (SD 2.7) in the sotalol group, and 3.6 years (SD 1.6) in the verapamil group.
Overall, the mean reduction in PVC burden on Holter recordings was − 4.4 percentage points (range − 46 to + 27 percentage points) in the patients treated with AAD, compared to − 4.2 percentage points (range − 21 to + 9 percentage points) in the control group. The reduction in PVC burden of the 5 groups is presented in Fig. 1. There was no relation between age and PVC burden in a linear regression model (p = 0.527). Patients in the flecainide group had a mean reduction of -13.8 percentage points (N = 10), in the beta-blockers group -1.7 percentage points (N = 18), in the sotalol group + 1.0 percentage points (N = 7) and in the verapamil group -3.9 percentage points (N = 11). The overall test from the generalized linear mixed model indicated significant differences in reduction of PVC burden between the five groups (four treatment groups plus control group) (p = 0,032). Looking at the pairwise comparisons of the treated patients versus the control patients, only the difference between the flecainide group and the control group was significant (p = 0,033).The four treatment groups were also tested in a generalized linear mixed model without the control group. In this overall test there was a significant difference between the four treatment groups (p = 0,023).
The groups were too small to be able to perform further statistical analyses of subgroups with different dosages of medication. One patient with LV dysfunction had -46 percentage points PVC reduction on flecainide therapy and full recovery of LV function. The PVC reduction was confirmed on multiple Holters, returned after discontinuation of flecainide and resolved again after restarting flecainide. Catheter ablation was not performed because during electrophysiology study the PVC focus was located deep in the papillary muscle.
During follow-up, a catheter ablation procedure was performed in 14 patients with a mean age of 14 years (SD 3.4 years). Indications for ablation were symptoms in combination with failure of medication, and/or LV dysfunction. Of these procedures 11 were successful, with the focus of the PVCs in the right ventricular outflow tract (RVOT), at the right ventricular (RV) free wall or tricuspid annulus. Unsuccessful ablation sides were at the papillary muscle or LV summit.