Junctional ectopic tachycardia (JET) may complicate the

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1 Amiodarone as a First-Line Therapy for Postoperative Junctional Ectopic Tachycardia Lubica Kovacikova, MD, PhD, Nina Hakacova, MD, Dusan Dobos, MD, Peter Skrak, MD, PhD, and Martin Zahorec, MD Intensive Care Unit, Children s Cardiac Center, Bratislava, Slovakia Background. Postoperative junctional ectopic tachycardia is a potentially life-threatening arrhythmia that is often resistant to conventional antiarrhythmic drugs. Amiodarone was suggested to be an adequate treatment; however, data regarding its efficacy and safety are limited. This study evaluated the efficacy of amiodarone in the first-line treatment of postoperative junctional ectopic tachycardia and assessed factors associated with failure of amiodarone therapy. Methods. The study included 40 pediatric cardiosurgical patients with postoperative junctional ectopic tachycardia. Intravenous amiodarone in 2-mg/kg boluses and, if necessary, as continuous infusion (10 to 15 g/kg/min), were used as the first-line therapy. Restoration of sinus rhythm or slowing of junctional ectopic tachycardia to a rate that allowed atrial or atrioventricular sequential pacing was considered as efficacy of therapy. Results. Amiodarone was effective in 18 patients (45%). Sinus rhythm was achieved in 7, and heart rate decreased in 11 patients from 180 (range, 173 to 200) to 142 (range, ) beats/min (p < ) and allowed effective pacing with atrioventricular synchrony. Higher arteriovenous oxygen saturation difference (p 0.007) and lower body temperature (p 0.02) were associated with failure of amiodarone therapy. Conclusions. Amiodarone as the first-line treatment was effective in almost half of the patients with postoperative junctional ectopic tachycardia. Higher arteriovenous oxygen saturation difference and lower body temperature were associated with failure of amiodarone therapy, and their presence may suggest more aggressive initial approach consisting of amiodarone combined with hypothermia. (Ann Thorac Surg 2009;88:616 23) 2009 by The Society of Thoracic Surgeons Junctional ectopic tachycardia (JET) may complicate the postoperative period in children who have undergone palliative or corrective operations for congenital heart disease. Although JET may be transient, it can be associated with high rates of mortality and morbidity if vigorous appropriate management is not instituted early after diagnosis [1 4]. Therapy starts with general measures such as correcting fever, electrolyte abnormalities, anemia, and hypovolemia, along with optimizing sedation and reducing inotropic drug administration. Specific therapeutic strategies include hypothermia and pharmacotherapy. Hypothermia was shown to be effective therapy for postoperative JET [5 7]; however, this approach requires artificial ventilation, deep sedation, and muscle paralysis. It also carries a risk of undesirable side effects such as immune dysfunction and hemodynamic alterations [8]. Pharmacologic interventions such as digoxin, intravenous procainamide, flecainide, and propranolol have been used in management of JET with varying degrees of success [1 4, 9 12]. The most encouraging results have been reported with intravenous amiodarone, and therefore, amiodarone was suggested as the possible first-line therapy of postoperative JET [13 17]. Data regarding its efficacy and safety are limited, however. Accepted for publication April 24, Address correspondence to Dr Kovacikova, Children s Cardiac Center, Limbova 1, Bratislava, , Slovakia; lkovacikova@yahoo.com. Since 1998 our treatment protocol for JET has consisted of intravenous amiodarone as the first-line therapy and induced hypothermia as the second-line therapy if amiodarone failed to treat JET. The primary hypothesis of this study was that amiodarone as a first-line pharmacologic therapy leads to restoration of sinus rhythm or significant slowing of the heart rate. The secondary hypothesis was that certain perioperative factors are predictive for failure of amiodarone therapy. Patients and Methods Patients with JET after operations for congenital heart disease admitted to the intensive care unit at the Children s Cardiac Centre in Bratislava, Slovakia, between January 1998 and December 2007 were considered for inclusion in this study. Included were patients with a JET rate higher than 170 beats/min (bpm) after correction of fever, electrolyte abnormalities, anemia and hypovolemia, optimizing sedation and inotropic support. Written consent was obtained from parents of all patients in accordance with relevant institutional guidelines. The research protocol of this prospective single-center study was approved by the Institutional Review Board Committee of Pediatric Cardiac Center and complies with the Declaration of Helsinki. Diagnosis of JET Diagnosis of JET was made from the surface and atrial electrocardiogram (Cardiovit AT-5, Schiller, Switzer by The Society of Thoracic Surgeons /09/$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg KOVACIKOVA ET AL 2009;88: AMIODARONE FOR JUNCTIONAL ECTOPIC TACHYCARDIA 617 Table 1. Primary Cardiac Diagnosis and Surgical Procedures for 40 Patients Treated for Junctional Ectopic Tachycardia Primary Cardiac Diagnosis No. Surgical Procedure VSD 11 Correction With aortic coarctation/hypoplasia 3 Correction With ASD secundum 2 Correction Tetralogy of Fallot and variants 8 Correction ASD primum 2 Correction Single atrium, MR, TR 1 Correction TAPVD 4 Correction Interruption of aortic arch 1 Correction Hypoplastic LV 1 DKS Sano Truncus arteriosus 1 Correction D-transposition of great arteries 1 Correction L-transposition of great arteries 1 VSD closure Hypoplastic left heart syndrome 3 Norwood, 2 Fibroelastosis resection, 1 a Double-inlet LV, pulmonary stenosis 1 Fontan a In borderline hypoplastic left heart syndrome. ASD atrial septal defect; DKS Sano Damus-Kaye-Stansel anastomosis plus Sano shunt; LV left ventricle; MR mitral regurgitation; TR tricuspid regurgitation; TAPVD total anomalous pulmonary venous drainage; VSD ventricular septal defect. land). JET was characterized by (1) tachycardia with a heart rate faster than 170 bpm, usually exhibiting a pattern of warm up at initiation, (2) a narrow QRS or wide QRS in the presence of surgically induced bundle branch block, and (3) the presence of atrioventricular dissociation with a ventricular rate greater than the atrial rate or retrograde 1:1 ventriculoatrial conduction. Therapy Protocol for JET First-line therapy with amiodarone and second-line therapy with hypothermia was used as described below: FIRST-LINE THERAPY WITH AMIODARONE. Amiodarone was administered according to protocol, where 2-mg/kg intravenous boluses were given over a 5 to 10 minutes, with a maximum total initial bolus dose of 10 mg/kg. After boluses, a continuous infusion of 10 to 15 g/kg/min was used, if necessary, with the dose and duration of infusion therapy at the discretion of the treating physician. If JET responded initially to amiodarone boluses, but later recurred, an additional 2-mg/kg dose was administered; however, the total daily bolus dose of amiodarone could not exceed 15 mg/kg. The efficacy of amiodarone therapy was defined as the restoration of sinus rhythm or the slowing of junctional rhythm to an acceptable heart rate that allowed hemodynamic improvement with atrial or atrioventricular sequential pacing. Failure of amiodarone therapy was defined as persistently rapid JET or late increases in the JET rate exceeding 170 bpm requiring escalation of therapy to hypothermia. Safety of amiodarone therapy was defined as absence of hemodynamic instability requiring intervention. SECOND-LINE THERAPY WITH HYPOTHERMIA. Core temperature was reduced to 31 to 35 C by using cooling blankets and insulated ice packs placed around the head and trunk. The patients were sedated, mechanically ventilated, and Fig 1. (Top row) Heart rate, (middle row) arterial blood pressure, and (bottom row) arteriovenous oxygen saturation difference over time in patients treated with (left panels) only amiodarone and in patients treated with (right panels) amiodarone, followed by hypothermia. Data are presented as box plot. The whiskers mark the 90th and 10th percentiles; the box edges mark the 75th and 25th percentiles; and the horizontal line marks the 50th percentile.

3 618 KOVACIKOVA ET AL Ann Thorac Surg AMIODARONE FOR JUNCTIONAL ECTOPIC TACHYCARDIA 2009;88: paralyzed to prevent shivering. The temperature was continuously monitored through a rectal thermistor. Data Collection Demographic, surgical, and hemodynamic data, and details related to JET and amiodarone therapy were collected longitudinally by completing forms developed for the study. Heart rhythm and rate, elapsed time from admission from the operating room until the JET occurrence, and type of atrioventricular conduction were assessed from records of continuous electrocardiographic (ECG) monitoring. The dose of amiodarone and the overall duration of continuous infusion of amiodarone therapy necessary for effective treatment of JET were calculated. Data on heart rate and arterial blood pressure were obtained at baseline and at 1, 2, 3, 6, and 12 hours after the initiation of treatment with amiodarone as well as the arteriovenous (AV) oxygen saturation difference at baseline and at 6 and 12 hours after the initiation of treatment with amiodarone. The number of patients with successful amiodarone therapy was assessed. Predictors of failure of amiodarone therapy were defined. Data on the duration and depth of hypothermia was assessed. Statistical Analysis Continuous data are presented as median and range. The t test was used for comparison of variables between the patients treated with amiodarone only and those who required hypothermia added to amiodarone therapy. A paired t test was used for time analysis of heart rate, blood pressure, and AV oxygen saturation difference. Univariate analysis (logistic regression and 2 test) was used to assess the factors associated with the need of escalation therapy to hypothermia. Significant risk factors were entered into a multivariate analysis using a forward stepwise logistic regression model to determine optimal coefficient of determination (R 2 ). Analysis was done with JMP 5.0.1a software (SAS Institute Inc, Cary, NC), and p 0.05 was considered significant. Results Between January 1998 and December 2007, 40 postoperative patients were identified with a JET rate exceeding 170 bpm after correction of fever, electrolyte abnormalities, anemia and hypovolemia, optimizing sedation, and reducing inotropic drug. These patients represent 1.4% of all cardiac surgical patients during that period. Median age of the study population was 2 months (range, 3 days to 72 months), and median weight was 3650 g (range, 2400 g to 16 kg). The underlying cardiac diagnoses and surgery are summarized in Table 1. The RACHS-1 (Risk Adjustment for Surgery for Congenital Heart Disease) category frequencies [18] were: category 1, 2.6%; category 2, 61.5%; category 3, 12.8%; category 4, 12.8%; category 5, 2.6%; and category 6, 7.7%. One patient, who had a borderline hypoplastic left heart syndrome and underwent resection of the endocardial fibroelastosis, could not be placed in any RACHS-1 category. JET began at median of 4 hours (range, 0 to 37 hours) after arrival in the intensive care unit. At the beginning of JET, the median body temperature of the patients was 36 C (range, 34 to 38.7 C), hypokalemia (potassium 3.5 mmol/l) was present in 6 patients (15%), hypocalcemia (calcium 1.09 mmol/l) in 10 (25%), and metabolic acidosis (base deficit 2.5) in 4 (10%). Median peak junctional rates were 187 bpm (range, 170 to 230 bpm). There was no difference in JET rate between neonates and older patients. Amiodarone Efficacy Treatment with amiodarone was effective in 18 patients (45%). Boluses of amiodarone with median dose of 3 mg/kg (range, 2 to 10 mg/kg) were effective in restoring sinus rhythm in 7 patients. In the remaining 11 patients, junctional rhythm persisted after amiodarone boluses of 8 mg/kg (range, 4 to 10 mg/kg) and continuous infusion of amiodarone with duration of 23 hours (range, 8 to 55 hours). However; the rate decreased from 180 bpm (range, 173 to 200 bpm) to 142 bpm (range, 133 to 155 bpm; p ) and allowed effective pacing with atrioventricular synchrony. The treatment with amiodarone alone was not sufficient in 22 patients (55%), and escalation to hypothermia was required. In these patients, initial amiodarone boluses at the dose of 10 mg/kg (range, 4 to 10 mg/kg) decreased the JET rate from 190 bpm (range, 170 to 230 bpm) to 162 bpm (range, 155 to 210 bpm; (p 0.02). The Table 2. Comparison of Patients Treated With Only Amiodarone and Patients Treated With Amiodarone Followed by Hypothermia Amiodarone Variable Amiodarone Hypothermia Mean (range) (n 18) (n 22) p Value Heart rate, bpm At baseline 180 ( ) 190 ( ) hour 156 ( ) 169 ( ) hours 145 ( ) 155 ( ) hours 145 ( ) 165 ( ) hours 144 ( ) 162 ( ) hours 141 ( ) 161 ( ) Blood pressure, mm Hg At the baseline 54 (40 66) 54 (25 81) hour 60 (50 87) 58 (34 75) hours 58 (54 71) 58 (47 77) hours 55 (51 79) 58 (52 90) hours 61 (51 85) 59 (51 90) hours 61 (46 74) 61 (47 89) 0.6 AV O 2 saturation difference, % At the baseline 27 (13 62) 42 (20 76) hours 27 (14 49) 43 (10 77) hours 26 (12 41) 37 (21 77) AV O 2 arteriovenous oxygen saturation.

4 Ann Thorac Surg KOVACIKOVA ET AL 2009;88: AMIODARONE FOR JUNCTIONAL ECTOPIC TACHYCARDIA 619 Table 3. Predictors of the Need for Hypothermia in the Management of Junctional Ectopic Tachycardia Factor Mean (range), or No. Amiodarone Only (n 18) Amiodarone Hypothermia (n 22) p Value by Analysis Univariate Multivariate R 2a AV O 2 sat difference, % 27 (13 62) 42 (20 76) Onset of JET, h 7 (1 30) 2 (0 37) TAPVD repair JET rate, beats/min 180 ( ) 190 ( ) Body temp, C 36.5 ( ) 36 ( ) Age, mon 4.0 ( ) 1.1 (0.06 9) Body weight, kg 4.0 ( ) 3.3 ( ) Cross-clamp time, min 52 (9 94) 48 (27 83) CPB, min 100 (45 149) 102 (55 198) RACHS category 2 (1 4) 2 (2 6) VSD b VSD RVOTO c A-V conduction type d 14/4 15/ a Coefficient of determination. b Operations involving perimembranous VSD closure. c Operations involving subarterial VSD closure and RVOTO resection in tetralogy of Fallot and its variants. d Atrioventricular dissociation/retrograde ventriculoatrial conduction. A-V atrioventricular; AV O 2 sat arteriovenous oxygen saturation; CPB cardiopulmonary bypass; JET junctional ectopic tachycardia; RACHS Risk Adjustment For Surgery for Congenital Heart Disease; RVOTO right ventricular outflow tract; TAPVD total anomalous pulmonary venous drainage; VSD ventricular septal defect. heart rate in 8 patients did not decrease adequately to allow atrial pacing, and therapy with hypothermia was initiated. The rate decrease in 14 patients was sufficient to allow pacing; however, late increases in the JET rate exceeding 170 bpm required escalation of therapy. The patients were cooled to a median temperature of 33 C (range, 31 to 35 C). Cooling was maintained for a median of 34 hours (range, 14 to 168 hours). In 20 of 22 patients, a continuous amiodarone infusion for a median duration of 50 hours (range, 12 to 132 hours) was also used to control heart rate. Hemodynamic Data In patients who responded to amiodarone, the heart rate decreased during the first hour after initiation of treatment from 180 bpm (range, 170 to 200 bpm) to 156 bpm (range, 105 to 176 bpm; p ). During the next hour, heart rate further decreased (p 0.01) and did not change significantly afterwards. In the patients who required treatment with amiodarone and hypothermia, the heart rate decreased during the first hour after initiation of treatment from 190 bpm (range, 170 to 230 bpm) to 169 bpm (129 to 214 bpm) (p ) and did not change significantly afterwards (Fig 1). At all time points after the initiation of treatment, the heart rate was higher in patients who required hypothermia than in patients who responded to therapy with amiodarone (Table 2). Mean blood pressure increased during the first hour after initiation of treatment in both groups and then did not change (Fig 1). There was no difference in mean blood pressure between patient groups (Table 2). AV oxygen saturation difference did not change at measurement times (Fig 1) in either group. AV was significantly higher in patients who required therapy with hypothermia compared with the patients who responded to amiodarone alone (Table 2). No deaths occurred in association with JET. In the patients who responded to amiodarone alone, permanent sinus rhythm occurred 24 hours (range 0.5 to 72 hours) after the initiation of the therapy compared with 42 hours (range, 4 to 264 hours; p 0.035) in the patients who required hypothermia. Amiodarone Safety During administration of amiodarone boluses, hypotension occurred in 28 patients, with good response to calcium or volume expansion in 23 and with a need to increase catecholamine support in 5 patients. One patient required cardiopulmonary resuscitation, including cardiac massage. No proarrhythmic effects of amiodarone, atrioventricular block, or bradycardia were documented. Predictors of Failure Predictors of amiodarone therapy failure are summarized in Table 3. By univariate analysis, patients who needed escalation therapy to hypothermia were younger, had lower body weight, early onset of JET, lower body temperature, and higher AV oxygen saturation difference. Also, there was an association between the need for hypothermia and repair of total anomalous pulmonary venous drainage. Multivariate regression analysis showed higher AV oxygen saturation difference and lower body temperature at the onset of JET to be the significant predictors of the need for escalation therapy to hypothermia. The forward stepwise regression model yielded a coefficient of determination (R 2 ) of 0.43 for higher AV oxygen saturation difference, early onset and high rate of JET, total anomalous pulmonary venous drainage repair, and low body temperature.

5 620 KOVACIKOVA ET AL Ann Thorac Surg AMIODARONE FOR JUNCTIONAL ECTOPIC TACHYCARDIA 2009;88: Comment JET Incidence The rate of JET after repair of congenital heart disease has been reported at 1% to 11% [19 23]. Our study group represents 1.4% of all cardiac postsurgical patients that are on the low end of reported rates. The spectrum of surgical interventions represents a general occurrence of congenital heart disease because our center covers the whole population of children in Slovakia with the entire spectrum of congenital heart diseases. Furthermore, during the study period, our center provided surgical and postoperative care to neonates with transposition of great arteries from Slovenia (5 to 7 patients annually) [24]. The study group, however, included only patients who required amiodarone therapy for a JET rate exceeding 170 bpm after correction of electrolyte, fluid, and temperature imbalance. Even though the study was not designed to identify risk factors associated with postoperative JET, it seems that its occurrence was related mostly to operations with an increased risk of direct trauma to the conduction system, such as tetralogy of Fallot and ventricular septal defect repair. This is in accordance with findings of previous investigators [11, 25]. In our study, JET occurred rarely in surgical repairs such as the Fontan procedure and the arterial switch operation, which were showed to be associated with JET occurrence [11, 15]. At our institution, atrial pacing wires are routinely placed after operations for congenital heart disease. The wires are used for pacing immediately when accelerated junctional rhythm occurs. We may speculate that optimizing an atrioventricular synchrony may prevent a progression to JET in some patients. Dorman and colleagues [26] suggest that magnesium depletion in the postoperative setting may significantly increase the risk that JET will develop. Our institution uses an aggressive protocol to detect and correct electrolyte and acid-base abnormalities. Magnesium sulphate is administered in the operating room and the intensive care unit immediately after any rhythm disturbance occurs, even if it is subtle. As a standard care, a bolus of magnesium sulfate (50 mg/kg) is administered into the bypass circuit after aortic unclamping in all patients. Efficacy of Amiodarone The main finding of the study is that amiodarone alone was sufficient in 45% of patients with postoperative JET. Hypothermia was needed as the second-line treatment in the remaining 55%. Several authors have studied the efficacy and safety of amiodarone in the management of postoperative arrhythmias [3, 13 16, 27 29]. Perry and colleagues [27] reported success in 13 of the 14 patients who received intravenous amiodarone for postoperative JET. A beneficial effect was noted during the initial amiodarone bolus (mean load, 6.3 mg/kg) where 5 patients converted to sinus rhythm and 8 slowed to the rate allowing atrial or atrioventricular sequential pacing. Raja and colleagues [16] reported the use of amiodarone as a bolus of 5 mg/kg and subsequent infusion to control JET. The JET rate reduced to less than 180 bpm within 2 hours in 10 of 16 patients. Saul and colleagues [28] conducted double-blind, randomized, dose-response study on the safety and efficacy of intravenous amiodarone for treatment of incessant tachyarrhythmias, including 28 patients with postoperative JET. Drug loading dosages were 1, 5 and 10 mg/kg during the first hour, plus a daily maintenance of 1, 5, and 10 mg/kg during the next 48 hours for low-, medium-, and high-dose groups, respectively. Success was achieved in 11.1%, 20.0%, and 33.3%, respectively, at the end of the loading dose and in 66.7%, 70.0%, and 83.3% at the end of the 48-hour treatment phase. The methodology in each of these studies varied significantly. Differences were related to size and duration of a loading dose and to the study population that may have included patients with arrhythmia refractory to first-line therapy with hypothermia or pharmacologic agents, or both. Also, the definitions of successful therapy were not standardized. Predictors for Amiodarone Failure Although univariate analysis showed multiple factors such as young age, low body weight, early onset of JET, low body temperature, high AV oxygen saturation difference, and total anomalous pulmonary venous drainage repair were associated with the need for hypothermia, the multivariate analysis showed only low body temperature and higher AV oxygen saturation difference were associated with the need for hypothermia. This is partly explained by the interdependence of these factors, in that smaller patient size is associated with enhanced difficulty in surgical access. Interdependence of early onset of JET and lower body temperature may be clarified by the tight body temperature control that is applied very early in the operating room when JET is suspected. We found a high AV oxygen saturation difference, a measure of low cardiac output state, was an independent and significant risk factor for the need of escalation therapy to hypothermia. This finding suggests that irrespective of heart rate, JET may be more resistant to amiodarone when a profound decrease in cardiac output accompanies tachycardia. An important question raised by many authors of previous reports is whether aggressive therapy is always indicated for JET. To quantify the hemodynamic effects of JET and the benefits of therapy is difficult [11]. However, several studies observed a trend toward lower arterial blood pressure and higher atrial pressures when rapid JET began [5, 6, 11, 16, 30, 31]. We detected an increase of blood pressure after initiation of treatment. Many centers suggest treatment of patients with JET rates of more than 170 bpm. Our results address that question because they show that the AV oxygen saturation difference might be better measure of the necessity for early treatment than JET rate alone. The AV oxygen saturation difference was significantly higher in patients who required hypothermia therapy compared with patients who responded to amiodarone not only before therapy but also 6 and 12 hours after

6 Ann Thorac Surg KOVACIKOVA ET AL 2009;88: AMIODARONE FOR JUNCTIONAL ECTOPIC TACHYCARDIA 621 therapy was initiated. We may speculate that low cardiac output is a cause of JET that does not respond well to therapy; however, low cardiac output may be a result of such resistant JET. Several studies have implicated the nature of the congenital heart disease and its repair as a major contributor to the genesis of JET [25, 31]. Our study demonstrates that surgical approaches may also influence responsiveness to therapeutic measures. An association between the need for hypothermia and total anomalous pulmonary venous drainage repair was observed. We speculate that this may be related to the age of our patients with total anomalous pulmonary venous drainage. All patients were neonates, and young age was a significant risk factor for the need of hypothermia. Furthermore, all patients had an infracardiac defect that requires a retraction of the heart out of the chest to allow dissection of the anomalous descending vertical vein. The remaining three surgical subgroups were (1) perimembranous ventricular septal defect closure, (2) operations involving subarterial ventricular septal defect closure with right ventricular outflow tract resection in tetralogy of Fallot and its variants, and (3) the subgroup of remaining procedures. When these groups were compared, no association was found between operations and a need for hypothermia. Cardiopulmonary bypass and aortic cross-clamp time, JET rate, and specific type of atrioventricular conduction did not have an influence on the responsiveness to amiodarone and the need for hypothermia in the management of JET. Side Effects of Amiodarone A low incidence of side effects was observed in previous retrospective studies [16, 17, 29]. However, the prospective study of Saul and colleagues [28] recorded a high rate of clinically significant adverse events, including hypotension, bradycardia, and atrioventricular block. Hypotension with subsequent intervention was common in our patients. This may be explained by a more rapid loading dose in our study compared with some previous studies and also because criteria for intervention were not strictly defined in neither our study nor in previous studies. Study Strengths and Limitations The strengths of this study are that it is prospective, single-institutional study marked by a consistency in two-staged treatment protocol throughout the study period and that it is a large reported patient group treated for JET with amiodarone as the only first-line treatment. An important question not addressed in this study is whether a different amiodarone treatment protocol would be more effective in the management of postoperative JET. Recommendations and Conclusions Amiodarone was effective in treatment of JET in 45% of patients. Use of amiodarone in these patients allowed avoidance of deep sedation, muscle paralysis, and possible adverse effects of hypothermia on hemodynamics and immune function. Amiodarone provided a return of sinus rhythm very shortly after initiation of therapy in some patients. In remaining 55% of patients, escalation of the therapy to hypothermia was required to facilitate slowing of JET to a rate at which atrial or atrioventricular sequential pacing was possible. The higher AV oxygenation saturation difference and low body temperature at the onset of JET were risk factors for a need of induced hypothermia as a second-line treatment. This analysis suggests a more aggressive protocol consisting of bolus doses, followed immediately by a continuous infusion for 24 to 48 hours, might reduce the need for escalation therapy to hypothermia. Several authors have advocated such treatment [13, 16, 17], and we began applying this approach after we analyzed the data reported here. Alternatively, a more aggressive approach consisting of amiodarone combined with hypothermia as the first-line therapy may be more effective if the risk of amiodarone therapy failure is present. References 1. Andreasen JB, Johnsen SP, Ravn HB. Junctional ectopic tachycardia after surgery for congenital heart disease in children. Intensive Care Med 2008;34: Braunstein PW Jr, Sade RM, Gillette PC. Life-threatening postoperative junctional ectopic tachycardia. Ann Thorac Surg 1992;53: Dodge-Khatami A, Miller OI, Anderson RH, Gil-Jaurena JM, Goldman AP, de Leval MR. Impact of junctional ectopic tachycardia on postoperative morbidity following repair of congenital heart defects. Eur J Cardiothorac Surg 2002;21: Shah MJ, Rhodes LA. Management of postoperative arrhythmias and junctional ectopic tachycardia. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 1998;1: Balaji S, Sullivan I, Deanfield J, James I. Moderate hypothermia in the management of resistant automatic tachycardias in children. Br Heart J 1991;66: Pfammatter JP, Paul T, Ziemer G, Kallfelz HC. Successful management of junctional tachycardia by hypothermia after cardiac operations in infants. Ann Thorac Surg 1995; 60: Wilken M, Paul T, Ziemer G, Kallfelz HC. Therapy of postoperative ectopic junctional tachycardia by surface hypothermia. Z Kardiol 1993;82: Bash SE, Shah JJ, Albers WH, Geiss DM. Hypothermia for the treatment of postsurgical greatly accelerated junctional ectopic tachycardia. J Am Coll Cardiol 1987;10: Gillette PC. Diagnosis and management of postoperative junctional ectopic tachycardia. Am Heart J 1989;118: Mandapati R, Byrum CJ, Kavey RE, et al. Procainamide for rate control of postsurgical junctional tachycardia. Pediatr Cardiol 2000;21: Walsh EP, Saul JP, Sholler GF, et al. Evaluation of a staged treatment protocol for rapid automatic junctional tachycardia after operation for congenital heart disease. J Am Coll Cardiol 1997;29: Mahmoud AB, Tantawy AE, Kouatli AA, Baslaim GM. Propranolol: a new indication for an old drug in preventing postoperative junctional ectopic tachycardia after surgical repair of tetralogy of Fallot. Interact Cardiovasc Thorac Surg 2008;7: Haas NA, Camphausen CK. Impact of early and standardized treatment with amiodarone on therapeutic success and

7 622 KOVACIKOVA ET AL Ann Thorac Surg AMIODARONE FOR JUNCTIONAL ECTOPIC TACHYCARDIA 2009;88: outcome in pediatric patients with postoperative tachyarrhythmia. J Thorac Cardiovasc Surg 2008;136: Haas NA, Plumpton K, Justo R, Jalali H, Pohlner P. Postoperative junctional ectopic tachycardia (JET). Z Kardiol 2004; 93: Perry JC, Knilans TK, Marlow D, Denfield SW, Fenrich AL, Friedman RA. Intravenous amiodarone for life-threatening tachyarrhythmias in children and young adults. J Am Coll Cardiol 1993;22: Raja P, Hawker RE, Chaikitpinyo A, et al. Amiodarone management of junctional ectopic tachycardia after cardiac surgery in children. Br Heart J 1994;72: Laird WP, Snyder CS, Kertesz NJ, Friedman RA, Miller D, Fenrich AL. Use of intravenous amiodarone for postoperative junctional ectopic tachycardia in children. Pediatr Cardiol 2003;24: Jenkins KJ, Gauvreau K, Newburger JW, Spray TL, Moller JH, Iezzoni LI. Consensus-based method for risk adjustment for surgery for congenital heart disease. J Thorac Cardiovasc Surg 2002;123: Delaney JW, Moltedo JM, Dziura JD, Kopf GS, Snyder CS. Early postoperative arrhythmias after pediatric cardiac surgery. J Thorac Cardiovasc Surg 2006;131: Rekawek J, Kansy A, Miszczak-Knecht M, et al. Risk factors for cardiac arrhythmias in children with congenital heart disease after surgical intervention in the early postoperative period. J Thorac Cardiovasc Surg 2007;133: Batra AS, Chun DS, Johnson TR, et al. A prospective analysis of the incidence and risk factors associated with junctional ectopic tachycardia following surgery for congenital heart disease. Pediatr Cardiol 2006;27: Hoffman TM, Wernovsky G, Wieand TS, et al. The incidence of arrhythmias in a pediatric cardiac intensive care unit. Pediatr Cardiol 2002;23: Pfammatter JP, Bachmann DC, Wagner BP, et al. Early postoperative arrhythmias after open-heart procedures in children with congenital heart disease. Pediatr Crit Care Med 2001;2: Hraska V, Podnar T, Kunovsky P, et al. Is a learning curve for arterial switch operation in small countries still acceptable? Model for cooperation in Europe. Eur J Cardiothorac Surg 2003;24: Dodge-Khatami A, Miller OI, Anderson RH, et al. Surgical substrates of postoperative junctional ectopic tachycardia in congenital heart defects. J Thorac Cardiovasc Surg 2002;123: Dorman BH, Sade RM, Burnette JS, et al. Magnesium supplementation in the prevention of arrhythmias in pediatric patients undergoing surgery for congenital heart defects. Am Heart J 2000;139: Perry JC, Fenrich AL, Hulse JE, Triedman JK, Friedman RA, Lamberti JJ. Pediatric use of intravenous amiodarone: efficacy and safety in critically ill patients from a multicenter protocol. J Am Coll Cardiol 1996;27: Saul JP, Scott WA, Brown S, et al. Intravenous amiodarone for incessant tachyarrhythmias in children: a randomized, double-blind, antiarrhythmic drug trial. Circulation 2005; 112: Plumpton K, Justo R, Haas N. Amiodarone for postoperative junctional ectopic tachycardia. Cardiol Young 2005;15: Grant JW, Serwer GA, Armstrong BE, Oldham HN, Anderson PA. Junctional tachycardia in infants and children after open heart surgery for congenital heart disease. Am J Cardiol 1987;59: Till JA, Ho SY, Rowland E. Histopathological findings in three children with His bundle tachycardia occurring subsequent to cardiac surgery. Eur Heart J 1992;13: INVITED COMMENTARY Junctional ectopic tachycardia (JET) is a serious postoperative arrhythmia that occurs in children undergoing palliative or corrective operations for congenital heart disease. A commonly used treatment algorithm for JET was first described by Walsh and colleagues [1] that uses a tiered approach in which general measures are used first, such as AV-synchrony and hypothermia, followed by a combined hypothermic and pharmacologic intervention. Kovacikova and colleagues [2] evaluated a protocol in which pharmacologic methods were used first. This is a descriptive study in which the authors prospectively treated JET systematically after surgical intervention for congenital heart disease in a single-center cardiac unit. During a 9-year period, 40 patients were recruited with a postoperative diagnosis of JET. Electrolytes, fluid, and temperature homeostasis were checked; then, all patients were treated with a standardized algorithm of 2 mg/kg boluses of amiodarone during a 5- to 10-minute period, up to 10 mg/kg, followed by a discretionary infusion. Second-line therapy was hypothermia to 31 to 35 C. Patients were sedated, intubated, and paralyzed for second-line therapy. The primary outcome measure was restoration of sinus rhythm or slowing of JET to acceptable heart rate that allows hemodynamic improvement or AV sequential pacing with no recurrence of JET after therapy. In this study, amiodarone was effective in treatment of postsurgical JET in 45% of patients. They describe hypotension in 70% of patients. One patient required cardiopulmonary resuscitation. Multivariate regression analysis identified higher A-VO 2 difference as the most significant predictor of amiodarone failure. This makes sense, because patients with low cardiac output will have high circulating catecholamines, the reduction of which will facilitate JET resolution. The major limitation to this study is the lack of a control group. However, Batra and colleagues [3] studied the reciprocal approach hypothermia first, followed by amiodarone. This is essentially the control group for the Kovacikova study [2]. They had the exact same response to therapy: 48% responded to hypothermia and then the rest to the addition of amiodarone. The same result was obtained by Walsh and colleagues [1], who used procainamide instead of amiodarone. Hoffman and colleagues [4] used a tiered approach, but only 39% required any intervention beyond fever reduction, sedation, and minimizing catecholamines. In summary, it seems that JET resolution is not an adequate therapeutic end point, because all tiered approaches have similar efficacy outcomes and spontaneous resolution rates are high. Side effects related to therapy and time to JET resolution are more appropriate outcome variables. A randomized trial comparing hypothermia or pharmacologic intervention vs combined therapy is needed. Until that trial is performed, a tiered 2009 by The Society of Thoracic Surgeons /09/$36.00 Published by Elsevier Inc doi: /j.athoracsur