1002 JACC Vol. 26, No. 4 October 1995:1002-7 Etficacy and Proarrhythmia of Oral Sotalol in Pediatric Patients JEAN PIERRE PFAMMATTER, MD,* THOMAS PAUL, MD, CHRISTINE LEHMANN, MD, HANS CARLO KALLFELZ, MD Hannover, Germany Objectives. This study sought to assess the efficacy of oral disease, sotaloi was effective in 84% of patients (completely in 9 of sotalol for various arrhythmias in pediatric patients and to 19 and partially in 7 of 19). Ventricular tachycardia was com- evaluate the incidence of proarrhythmia and systemic side effects. pletely (3 of 11) or partially (4 of 11) controlled in 64% of children. Background. Sotalol is a beta.adrenergic blocking agent with Proarrhythmia occurred in seven patients (10%) and consisted of additional class III antiarrhythmie properties. Experience in symptomatic bradycardia from sinoatrial block and high grade pediatric patients is limited. Data concerning the incidence of atrioventricular (AV) block, respectively, in two children; asymp- proarrhythmia in children are lacking. tomatic high grade AV block in one; torsade de pointes in one; and Methods. Seventy-one pediatric patients (mean age 7.3 years) relevant increased ventricular ectopic activity in three. Proar- with various supraventricular and ventricular tachyarrhythmias rhythmia required drug discontinuation in four patients. Mean were treated with oral sotaiol. All the patients were admitted to duration of treatment for all patients was 18 months (range 1 to the hospital for initiation of sotalol therapy. Antiarrhythmic and 40). proarrhythmic effects of sotalol were assessed by daily surface Conclusions. Sotalol was an effective antiarrhythmic drug for a electrocardiograms (ECGs) during the in-hospital phase and by wide range of pediatric tachyarrhytlunias. The considerable num- serial Holter monitoring. ber of patients with proarrhythmic effects indicates the need for Results. Sotalol was either completely (27 [66%] of 41 patients) initiation of treatment on an inpatient basis and close monitoring or partially effective (11 [27%] of 41) in 38 (93%) of 41 patients by serial Holter electrocardiography. with supraventricalar reentrant tachycardias. In patients with (J Am CoU Cardio11995;26:1002-7) atrial flutter predominantly after operation for congenital heart Sotalol hydrochloride is a noncardioselective beta-adrenergic Methods blocking agent with additional class 1II antiarrhythmic proper- Patients. From July 1987 to July 1994, all 71 infants and ties (prolongation of action potential duration) (1,2). Sotalol children who were treated at our institution with oral sotalol has been proved to be an effective antiarrhythmic agent in adult patients treated for ventricular tachyarrhythmias (3-6) for symptomatic supraventricular and ventricular arrhythmias and atrial flutter (7) and in the short- (8) and long-term were enrolled in the study protocol. Patients >16 years old treatment of supraventricular reentrant tachycardias (9,10). were included in this study only if they had congenital heart The few clinical studies with oral sotalol in the pediatric age disease. group have reported encouraging results (11-13), but experi- The study protocol had been approved by the hospital's ence with this drug in infants and children is still limited. scientific committee. Informed consent was obtained from Treatment of adult patients with oral sotalol has been shown to parents of all children included in the study. be associated with proarrhythmic effects in 3% to 5% of Arrhythmia diagnosis. The type of arrhythmia was diag- patients (2), In pediatric patients the incidence of proarrhyth- nosed according to established criteria (14,15) either by 12- mia has not been systematically investigated. lead electrocardiography during tachycardia or by 24-h Holter The purpose of the present study was to evaluate prospec- electrocardiography, in some instances by transesophageal tively the effectiveness as well as incidence and type of electrocardiography. Invasive electrophysiologic study was per- proarrhythmic events in pediatric patients treated with oral formed for diagnostic purposes in 11 children and for curative sotalol. transcatheter ablation of the underlying arrhythmogenic sub- strate in 13. Sotaloi protocol. Oral sotalol treatment was started on an inpatient basis. Baseline examinations before initiation of From the Department of Pediatric Cardiology', Children's Hospital, Han- nover Medical School, Hannover, Germany. sotalol included a 12-lead electrocardiogram (ECG), a 24-h Manuscript received November 21, 1994; revised manuscript received May 9. Holter monitor, echocardiography (two-dimensional and color 1995, accepted May 15, 1995. Doppler) and a blood sample for evaluation of renal and liver *Present address and address for corresoondence: Dr. Jean Pierre Pfammat- ter, Department of Pediatric Cardiology. Children's Hospital, Freiburgstrasse, functions as well as a complete blood count. All these tests CH-3010 Berne, Switzerland. were repeated after 5 to 7 days to sotalol treatment before ©1995 by the American College ol Cardiolo~ 0735-1097/95/$9.50 0735-1097(95)00268-9 JACC Vol. 26, No. 4 PFAMMATI'ER ET AL. 1003 October 1995:1002-7 SOTALOL IN CHILDREN hospital discharge. Echocardiography was repeated in all pa- Table 1. Patient Data Related to Diagnosis of Underlying tients after 3 months of therapy. Blood tests were repeated Rhythm Disturbance only sporadically and if indicated by the patient's history or Structural Heart Disease symptoms. In patients who had been treated with another No. of Mean (-SD) No. of antiarrhythmic drug before, oral sotalol was started after the Diagnosis Pts Age (yr) Pts Type (no. of pts) previous antiarrhythmic drug had been discontinued for at least five drug half-lives. This condition could not be fulfilled WPW 17 3.8 -+ 4.2 5/17 Ebstein (3), ASD (1), L-TGA (1) for two patients who had been treated with amiodarone before PJRT 1 0.1 0 the initiation of sotalol. Digoxin was maintained in those CAP 16 5.0 -+ 4.0 3/16 DORV, s/p (1); SV, s/p patients who had already been treated with this substance. (1); L-TGA, s/p (1) Oral sotalol was started at a dose of 2 mg/kg body weight per AVNRT 7 9.5 -+ 2.6 1/7 SV/Fontan (1) day in three divided doses. In case of persistent arrhythmia, the AFL 19 10.6 -+ 6.4 18/19 Ebstein, s/p (3); D-TGA/ dosage was increased in 1- to 2-mg/kg steps under continuous Mustard (10); L-TGA, s/p (1); PS, s/p (1); ECG monitoring at 3-day intervals until the desired effect or Patr, s/p (1); TAPVC, the maximal dose of 8 mg/kg per day was reached. Only dose s/p (1); ASD, s/p (1) adjustments to weight were made on an outpatient basis. VT 11 9.3 +_ 7.0 6/11 IDC (3); myocarditis (1); Increases in dosage for lack of drug effect were made during a TOF, s/p (1); L-TGA, hospital stay. Determination of serum levels of sotaloi was not s/p (1) available during the study. Total 71 7.3 _+ 5.8 33/71 Criteria for efficacy. Sotalol treatment was considered suc- AFL = atrial flutter; ASD = atrial septal defect; AVNRT = atrioventricular cessful if the arrhythmia was completely suppressed as evalu- node reentrant tachycardia; CAP = concealed accessory atrioventricular path- ated by symptoms and repeated Holter monitoring. Partial way; DORV = double-outlet right ventricle; Ebstein = Ebstein's anomaly; effectiveness was defined as a decrease in frequency or dura- Fontan =Fontan operation; IDC = idiopathic dilated cardiomyopathy; Mustard = Mustard operation; Patr = pulmonary atresia; PJRT = permanent junctional tion of tachycardias or a reduction in maximal heart rate reciprocating tachycardia; PS = pulmonary stenosis; Pts (pts) = patients; s/p = during tachycardia or improvement of symptoms. If a partial postoperative; SV = single ventricle; TAPVC = total anomalous pulmonary vein effect was obtained, dosage was not increased further if connection; TGA - transposition of great arteries; TOF = tetralogy of Fallot; residual episodes of the arrhythmia were clinically well toler- VT = ventricular tachycardia; WPW = Wolff-Parkinson-White syndrome. ated and the result was judged satisfactory by the child, the parents and the investigators. After initiation of sotalol ther- apy, Holter monitoring to evaluate sotalol response was per- patients with QTc prolongation to ->0.44 and to ->0.46 with formed before hospital discharge (usually 5 to 7 days after increasing dose of sotalol). Within-patient comparisons were starting sotalol), at 1 month and then at 3- to 6-month intervals made using the paired t test. Independent variables were as well as after dose adjustments on an outpatient basis. compared using the unpaired t test. A p value <0.05 was ECG characteristics. Baseline ECG recordings during si- considered statistically significant. nus rhythm and without any medication except for digoxin were compared with those during sotalol therapy for changes in duration of PR interval, QRS duration and corrected QT Results interval (QTc) in relation to dosage of sotalol. For better Patient characteristics. Of the 71 patients (24 female, 47 comparison of these variables, the ECGs were usually re- male), the diagnosis was supraventricular reentrant tachycar- corded before the following dose of sotalol. The QT interval dia in 41 (Wolff-Parkinson-White syndrome in 17, concealed was measured in lead II (16), and rate correction (QTc) was accessory pathway in 16, atrioventricular (AV) node reentrant calculated according to Bazzett's formula (17). Patients with tachycardia in 7, permanent junctional reciprocating tachycar- predominantly pacemaker-induced QRS complexes, and pre- dia in 1). Nineteen patients had recurrent episodes of atrial excitation and the two patients with previous amiodarone flutter (1 congenital, 18 postoperative). Eleven patients had treatment were excluded from these comparisons. The influ- ventricular tachycardia. ence of sotalol on heart rate was evaluated by comparing Mean [_+SD] age at initiation of sotalol was 7.3 + 5.8 years minimal and maximal as well as mean heart rate in the (range 0.1 to 19.9) for the whole group. Mean age was clearly individual patient during 24-h Holter electrocardiography be- lower in patients with Wolff-Parkinson-White syndrome (3.8 fore and during sotalol treatment.