Progress in Pediatric Cardiology

Transcription

1 Progress in Pediatric Cardiology 35 (2013) Contents lists available at SciVerse ScienceDirect Progress in Pediatric Cardiology journal homepage: Review Junctional ectopic tachycardia: Current strategies for diagnosis and management Anjan S. Batra a,b,, Nivedita Mohari c,d a Division of Pediatric Cardiology, Children's Hospital of Orange County, Orange, CA, United States b University of California at Irvine, Orange, CA, United States c Division of Pediatric Critical Care, Harbor-UCLA Medical Center, Los Angeles, CA, United States d Division of Pediatric Critical Care, Children's Hospital of Orange County, Orange, CA, United States article info abstract Keywords: Junctional ectopic tachycardia Congenital heart disease Post-operative Congenital Junctional ectopic tachycardia (JET) is a unique type of supraventricular arrhythmia defined by narrow QRS complex and atrioventricular (AV) dissociation or retrograde atrial conduction in a 1:1 pattern. JET has two forms of presentations: occurring immediately after surgery (post-operative) or a primary idiopathic form presenting in infancy (congenital). Post-operative JET is a potential life threatening tachycardia that mainly occurs after surgical correction of congenital heart defects. In general, it is a self-limiting disorder that usually resolves within one week. However, it can be a potentially serious arrhythmia, associated with hemodynamic compromise and a high morbidity and mortality. Congenital JET occurs in the first six months of life and is usually persistent and sometimes sporadic. Mortality with congenital JET has also been reported to be high. It is thought that both the presentations are due to abnormal automaticity of the AV node or proximal bundle of His. However, the risk factors, etiology and management of these two forms of JET are different. This manuscript reviews the literature on the incidence and risk factors of both forms of JET and current strategies for the diagnosis and management of each form Elsevier Ireland Ltd. All rights reserved. 1. Introduction 2. Post-operative JET Junctional ectopic tachycardia (JET) is a unique type of supraventricular arrhythmia defined by narrow QRS complex and atrioventricular (AV) dissociation or retrograde atrial conduction in a 1:1 pattern. JET has two forms of presentations: occurring immediately after surgery (post-operative) or a primary idiopathic form presenting in infancy (congenital). Post-operative JET is a potential life threatening tachycardia that mainly occurs after surgical correction of congenital heart defects. In general, it is a self-limiting disorder that usually resolves within one week. However, it can be a potentially serious arrhythmia, associated with hemodynamic compromise and a high morbidity and mortality. Congenital JET occurs in the first six months of life and is usually persistent and sometimes sporadic [1]. Mortality with congenital JET has also been reported to be high. It is thought that both the presentations are due to abnormal automaticity of the AV node or proximal bundle of His; however, the risk factors, etiology and management of these two forms of JET are different. This manuscript reviews the literature on the incidence and risk factors of both forms of JET and current strategies for the diagnosis and management of each form. Corresponding author at: Division of Pediatric Cardiology, Children's Hospital of Orange County and University of California at Irvine, 455 S Main Street, Orange, CA 92868, United States. Tel.: ; fax: Incidence Among the patients undergoing surgery for congenital heart disease, the average incidence of JET in the post-operative period for all congenital heart defects is reported to be between 2.7 and 10.2% (Table 1) [2 9]. The incidence varies with the underlying defect, type of repair and the surgical center and has been reported to be as high as 22% after the repair of tetralogy of Fallot [10] Risk factors Various recent reports have reiterated the earlier identification of younger age, higher inotropic use, longer bypass times and type of surgery as risk factors for post-operative JET (Table 1). Recent studies have also shed light on the molecular and genetic basis of JET Age Among the patients who developed post-operative arrhythmias, patients with JET were more likely to be younger [2,4,5,7 9] (Table 1). Neonatal AV nodal tissues in contrast to adolescent AV nodal cells or neonatal sinoatrial nodal cells have been shown to display a significant increase in subthreshold electrical fluctuations and variation of the peak-to-peak action potential intervals in response to ischemia reperfusion in a cellular model[11]. In immunohistochemical studies, /$ see front matter 2012 Elsevier Ireland Ltd. All rights reserved.

2 50 A.S. Batra, N. Mohari / Progress in Pediatric Cardiology 35 (2013) the expression of channel proteins (hyperpolarization-activated, cyclic nucleotide modulated channels) correlating with enhanced automaticity is more widespread in neonatal AV nodal cells in comparison to adult AV nodal cells [12]. These have been hypothesized as potential mechanisms of JET in younger patients Inotrope use Several studies have reported the higher inotropic use to be associated with JET (Table 1). Andreasen et al. and Batra et al. have reported higher inotrope scores in patients who have post-operative JET [5,7] (Table 1). Inotrope score is calculated by taking into account relative potencies of dopamine, dobutamine, epinephrine, norepinephrine and milrinone. Both dopamine [9] and milrinone [4] have been reported to be independently associated with post-operative JET. The authors postulated that the phosphodiesterase inhibition action of milrinone along with β-adrenergic stimulation by agents such as epinephrine and dopamine, might play an additive or even synergistic role in the evolution of postoperative JET. Disruptions in camp-dependent phosphorylation with use of inotropes and milrinone and the resultant intracellular calcium handling derangements may also be potential mechanisms [13,14]. Preliminary studies have shown that in cellular models, when spontaneous calcium transients were measured by confocal microscopy, neonatal AV nodal cells showed a severe disruption of waveform regularity following post-ischemic dopamine application [11] Cardiopulmonary bypass times Longer cardiopulmonary bypass times have been shown to be independently associated with post-operative JET in various studies (Table 1). The duration of cardiopulmonary bypass increasing the risk of JET reported in various studies shows wide variation. It is believed to be caused by ischemia reperfusion injury of the AV node [11]. The injury to the AV node and its subsequent automaticity is hypothesized to result from direct trauma or infiltrative hemorrhage to the conduction system [15] Type of surgery The types of surgical repair at greatest risk for developing JET varies between institutions and is clearly multifactorial. However, reportedly patients undergoing surgeries for ventricular septal defect closure, arterial switch operation, AV canal repair, tetralogy of Fallot and the Norwood operation appear to have a greater risk of developing JET [2,3,7,8]. Although many studies have reported an incidence of JET of 15 22% following surgery for tetralogy of Fallot [10,16 18], a recent study from Texas Children's Hospital reported a very low incidence of JET (2.3%) after tetralogy of Fallot repair with right ventricular infundibulum sparing surgery [19] Genetic predisposition A recent study [20] evaluated the association of angiotensinconverting enzyme insertion/deletion (ACE I/D) polymorphism with postoperative JET. The common ACE deletion polymorphism was associated with a greater than 2-fold increase in the odds of developing JET in children undergoing surgical repair of atrioventricular septal defect, tetralogy of Fallot, ventricular septal defect or the Norwood and arterial switch procedures. These findings may support the potential role of the renin angiotensin aldosterone system in the etiology of JET Diagnosis Diagnosis of JET is made by the typical electrocardiographic (ECG) tracing of narrow QRS-complexes at a rate of 170 to 260 heartbeats per minute and AV-dissociation where the atrial rate is slower than the ventricular rate (Fig. 1). The ECG tracing may also show retrograde 1:1 ventriculoatrial conduction (Fig. 2). If p-waves are not visible, then ECG using atrial leads can be performed. JET usually shows a variable rate, a warm up phase at its onset and a cool down phase at its termination (Fig. 2). In cases where the diagnosis of JET is still not clear, adenosine can be helpful to differentiate it from atrial flutter or fibrillation, reentrant tachycardia, ectopic atrial tachycardia or sinus tachycardia. In JET, adenosine will block the retrograde AV conduction and transiently slow the atrial rate but not impair the ventricular rate [21] (Fig. 3). In most other arrhythmias, adenosine will either terminate the tachycardia or transiently slow the ventricular rate and expose a faster atrial rate. Table 1 Incidence and risk factors associated with postoperative JET. Study Type of study N n (%) Risk factors of post operative JET Gebauer et al. (2011) [2] Retrospective (2.7%) Younger age (median 0.25 vs years; p=0.001) Longer cardiopulmonary bypass time (median vs. 91 min; p=0.001) Surgery involving closure of ventricular septal defect (100%) Mildh et al. (2011) [3] Retrospective (5%) Longer cardiopulmonary bypass time (138 vs. 119 min; p=0.002) High body temp (38.0 vs C; p=0.013) a High troponin (3.7 vs. 2.1 μg/l; pb0.001) Norepinephrine use (23/51 vs. 35/130, p=0.019) a Surgery involving closure of ventricular septal defect (65%) Smith et al. (2011) [4] Prospective (10%) Younger ageb1 month (OR 2.9, 95% CI: ; pb0.001) Longer cardiopulmonary bypass time (138 vs. 92 min; p=0.003) Milrinone use (93% vs. 65% p=0.007) Andreasen et al. (2008) [5] Prospective (10.2%) Younger age (median 4.5 vs months; p valueb0.001) Longer cardiopulmonary bypass times>90 min (OR 2.6; 95% CI: ) Higher inotrope score (9.2 vs. 0) (OR 2.6; CI ) High creatine kinase (CK)-MB Chaiyarak et al. (2008) [6] Prospective (9.4%) Longer cardiopulmonary bypass time Redo-operation Batra et al. (2006) [7] Prospective (8%) Younger age (2.75+/ 2.44 vs / 7.25 years; pb0.01) Longer cardiopulmonary bypass times (126+/ 50 vs. 85+/ 73; pb0.01) Higher inotrope score (6.26+/ 7.55 vs / 8.11; pb0.01) Delaney et al. (2005) [8] Prospective (8.5%) Younger age (22 vs. 45 months) Longer cardiopulmonary bypass time (189 vs. 109 min) Longer aortic cross clamp time (105 vs. 44 min) Hoffman et al. (2002) [9] Prospective (5.6%) Younger age (b6 months) Longer cardiopulmonary bypass times ( 75 min) Dopamine use postoperatively at dose-3 to 7.5 μg/kg/min (OR 6.2 p 0.01) n number of patients with JET. a Significant on univariate analysis, not significant on multivariate analysis.

3 A.S. Batra, N. Mohari / Progress in Pediatric Cardiology 35 (2013) Fig. 1. Rhythm strip of atrial electrocardiogram ( p waves, QRS complexes) showing junctional ectopic tachycardia with narrow complex QRS and AV dissociation Management Post-operative JET is usually self-limited and well tolerated, but with the simultaneous depression of myocardial function following cardiopulmonary bypass surgery and loss of AV synchrony, it may warrant aggressive treatment (Fig. 4). Therapy starts with general measures such as correcting fever, electrolyte abnormalities, anemia, and hypovolemia. Optimizing sedation and reducing inotropic drug administration are also important general strategies. Specific therapy with pharmacotherapy and cooling is instituted for restoration of sinus rhythm or slow the rate to allow atrial pacing at a slightly faster rate to augment cardiac output. Ablation and extracorporeal membrane oxygenation have been reported in the literature as rescue therapies but are rarely warranted Pharmacotherapy The most encouraging results have been reported with intravenous amiodarone (Table 2). Kovacikova et al. reported that out of 40 patients in their study, treatment with amiodarone was effective in 18 patients (45%) [22]. Sinus rhythm was restored in 7 patients by boluses of amiodarone with median dose of 3 mg/kg (range, 2 to 10 mg/kg). Continuous infusion of amiodarone with average duration of 23 h (range, 8 to 55 h) and amiodarone boluses decreased the heart rate from 180 beats per minute (range ) to 142 (range ) (p ) and allowed effective atrial pacing with AV synchrony in the remaining 11 patients. Cuenca Peiró et al. observed that among the 22 patients with JET followed at their center from 2006 to 2010, 16 responded to general measures [17]. Of the remaining 6, all of them responded to amiodarone. Plumpton et al. retrospectively reviewed the data of all the pediatric patients who received amiodarone post-operatively at their institution over an 8-year period for JET [23]. The analysis revealed that in 13 of the 15 patients, amiodarone controlled tachycardia. Kovacikova et al. noted hypotension with use of amiodarone in 28 of 40 patients [22]. The hypotension responded to calcium or volume expansion in 23 and increase catecholamine support in 5 patients. One patient required cardiopulmonary resuscitation for hypotension. No proarrhythmic effects of amiodarone including atrioventricular block or bradycardia were documented. The other antiarrhythmics reported in the past as effective for JET are procainamide [26], flecainide [27], propafenone [28] and esmolol. Chrysostomou et al. [29] reported their success in management of JET with dexmedetomidine. In this study, six patients developed JET during the early postoperative phase. The average JET rate before starting dexmedetomidine was 197 which decreased to 165 within an average of 67 min (range of min) of administering dexmedetomidine. Five of these patients received dexmedetomidine as a first-line treatment and one as a rescue. The loading dose of dexmedetomidine used was 0.1 to 0.2 mcg/kg/min and a maintenance infusion rate of 0.8 to 1.3 mcg/kg/h. One patient remained in junctional accelerated rhythm and all others had a conversion to normal sinus rhythm within a mean of 39 h (range 13 to 88 h) Cooling Cooling is one of the general measures for management of JET. It was first reported in 1987 as being effective in controlling the rate of greatly accelerated junctional ectopic tachycardia after open heart surgery in three infants [30]. Kovacikova et al. recently reported that escalation of active cooling to 33 C (range, 31 to 35 C) was effective in terminating JET in 14 of the 22 patients (n=22) in whom amiodarone alone was not effective [22]. Cooling techniques involving use of cooling blankets and 4 C normal saline infusions to a target central temperature of C and paralysis to prevent shivering has been reported to be safe and effective to induce therapeutic hypothermia to treat children with postcardiotomy JET [31] Pacing If the JET rate is slow, pacing alone may be adequate to achieve AV synchrony and improve hemodynamics. In others, pharmacotherapy and cooling may be warranted to slow the junctional rate before pacing can be initiated. The options for pacing are atrial (AOO) and atrioventricular sequential pacing [22]. Another possibility is V A sequential pacing by swapping the wires around so the temporary pacing box thinks that the ventricle signal is an atrial signal; it then senses the ventricle and paces the atrium. Thus, the effective mode is AVT. A short (100 ms) postventricular atrial refractory period (PVARP) and a long VA-delay (AV interval) has to be used and adjustment has to be made to achieve a maximum increase in arterial pressure by optimal AV resynchronization [32] Prophylactic treatment A few studies have reported significant results with pre- or intraoperative interventions to decrease the incidence of JET. At the University of Arkansas for Medical Sciences, in mid-2007, a strategy of prophylactic amiodarone continuous infusion was adopted for patients undergoing primary tetralogy of Fallot repair [24]. In the Fig. 2. Rhythm strip with an atrial electrocardiogram (arrows) showing junctional ectopic with 1:1 retrograde ventriculoatrial conduction during the junctional tachycardia. The tachycardia shows a variable rate, a warm up phaseatitsonsetanda cool down phase at its termination.

4 52 A.S. Batra, N. Mohari / Progress in Pediatric Cardiology 35 (2013) Fig. 3. ECG of JET showing the block of retrograde AV conduction with administration of adenosine (arrow), transient slowing of the atrial rate (A) but not the ventricular rate (N). operating room, at the time of re-warming during cardiopulmonary bypass amiodarone infusion was started at a rate of 2 mg/kg/day and continued for 48 h. Chart review of 63 consecutive patients undergoing primary tetralogy of Fallot repair between 2005 and 2009 revealed that 20 patients received prophylactic amiodarone and 43 patients did not. The incidence of JET was 10% in the patients who received prophylactic amiodarone compared with 37% in the patients that did not. Manrique et al. reported that the incidence of JET is reduced by supplementation of magnesium sulfate during the re-warming phase of cardiopulmonary bypass after pediatric cardiac surgery in a dose dependent manner [25]. They performed a randomized, double-blind, controlled trial in 99 children. Magnesium sulfate or placebo was administered during the re-warming phase of cardiopulmonary bypass with 29 patients receiving placebo, 30 patients receiving 25 mg/kg of magnesium sulfate and 40 patients receiving 50 mg/kg of magnesium sulfate. None of the patients who received 50 mg/kg of magnesium sulfate had JET. Patients receiving placebo had significantly higher incidence of JET than the group which received 25 mg/kg of magnesium sulfate (17.9% vs. 6.7%). In a retrospective analysis of 109 patients undergoing complete repair of tetralogy of Fallot, the incidence of postoperative JET was significantly lower in patients on prophylactic propranolol (21%) when compared to patients who were not on propranolol (38%) [18]. Postoperative Junctional Ectopic Tachycardia General measures Adequate sedation Normalize electrolytes Decrease inotropes Cooling Attempt AAI /AOO pacing If unsure of diagnosis: atrial ECG, adenosine IV Amiodarone bolus 1 mg/kg over 10 mins Max: 5 mg/kg over 60 mins Assess efficacy every 10 mins efficacy = NSR or slow enough JET to pace at acceptable rate Very good Good-fair None Discontinue further IV Amiodarone boluses IV Amiodarone infusion 5 mcg/kg/minute Max: 10 mcg/kg/minute Assess efficacy Good-fair None Temporary pace (A Pace V sense mode) Dexmedetomidine 1 mcg/kg load, 1 mcg/kg/hour infusion Magnesium mg/kg over 10 minutes Procainamide 7-10 mg/kg over minutes, mcg/kg/minute infusion; levels at 4 hours Esmolol mcg/kg/minute infusion after load Assess efficacy after each step None Consider extracorporeal membrane oxygenation, ablation Fig. 4. Management protocol of post-operative JET. AAI (atrial pace atrial sense mode), AOO (atrial pace mode), NSR (normal sinus rhythm).

5 A.S. Batra, N. Mohari / Progress in Pediatric Cardiology 35 (2013) Table 2 Management of post-operative JET. Study Type of study Age (years) N Intervention Outcome Kovacikova et al. (2009) [22] Prospective Neonate 6 40 Intravenous amiodarone 45% a Cuenca Peiró et al. (2011) [17] Retrospective 22 Intravenous amiodarone 100% a Plumpton et al. (2005) [23] Retrospective Neonate Intravenous amiodarone 87% a Imamura et al. (2012) [24] Retrospective Neonate 1 63 Intraoperative amiodarone vs. 10% vs. 37% b no amiodarone during cardiopulmonary bypass Manrique et al. (2010) [25] Randomized Neonate High dose vs. low dose vs. no magnesium during 0% vs. 6.7% vs. 17.9% b double-blind controlled cardiopulmonary bypass Mahmoud et al. (2008) [18] Retrospective Neonate Preoperative propranolol vs. no propranolol 21% vs. 38% b a b Percent of patients in whom the pharmacological intervention was effective in management of JET after failure of general measures. Percent of patients with post-operative JET Ablation and extracorporeal membrane oxygenation Case reports have reported successful management of post-operative JET with ablation [33,34]. Ablation is, however, a rescue therapy after failure of medical management in hemodynamically unstable patients. Extracorporeal membrane oxygenation is another rescue therapy for JET that is rarely needed. Recent retrospective reviews at single tertiary care pediatric hospitals have reported patients in whom extracorporeal membrane oxygenation was successfully used as rescue therapy for JET [35,36]. 3. Congenital JET 3.1. Incidence The congenital form of JET usually occurs in the first six months of life. This form of JET is rare when compared to postoperative JET and reports on congenital JET in the literature are limited to a few retrospective analysis [1,37] and case series [38 42]. Unlike the postoperative variety that is usually self-limiting, this form presents as a persistent sustained form lasting up to 90% of the time [37] Risk factors Congenital JET has been reported in association with complete heart block in the fetus. Dubin et al. reported JET in five infants born to mothers with positive serology for anti-ssa and anti-ssb [43]. They proposed anti-ssa and anti-ssb autoantibodies mediated inflammation of conduction system in fetal or neonatal life as the etiology of subgroup of patients with congenital JET. Among 53 fetuses referred to a tertiary care center for persistent arrhythmia, the incidence of JET was reported to be 30% among fetuses with 3 AV block [44] Diagnosis Collins et al. in a retrospective analysis of congenital JET from 22 centers found that the majority of patients (60%; 56 of 94) had a rapid or irregular heart rate sensed by the patient or evaluated on physical examination [1]. Congestive heart failure was found in 16% (15 of 94). Fetal tachycardia was diagnosed in 17% (16 of 94), with 4 of these patients having signs of hydrops. A case series of 7 patients with congenital JET from Argentina reported that 2 of the 7 patients presented with dilated cardiomyopathy [45]. In limited centers, fetal magnetocardiography is being used in the evaluation of at risk fetuses that are found to have irregular heartbeats to diagnose JET [44] Management Congenital JET usually requires specific therapy with medications or ablation (Table 3). Amiodarone has been reported to be the most commonly used antiarrhythmic for congenital JET. A large international multicenter retrospective outcome study of pediatric patients treated for congenital JET discovered that amiodarone was effective in 60% of patients as a single agent or in combination with other antiarrhythmics [1]. Beta blocker (as a single agent or in combination) was effective in 22% of patients. This study also reported that concomitant administration of 2 antiarrhythmic medications was required in 62% of patients. Of the patients with congenital JET, 52% underwent invasive electrophysiology studies with the intention of catheter ablation of the junctional focus. The indication for ablation was largely heart failure or refractory JET for patients undergoing radiofrequency ablation and elective for those undergoing cryoablation. Initial success (82% vs. 85%) and recurrence rates (13% vs. 14%) were similar for radiofrequency and cryoablation in this study. Similar success rates have been reported in other case series (Table 3). Ablation has also been performed in neonates by introducing a single catheter for detection, stimulation and ablation [41,42]. Mortality rate for congenital JET was reported to be 34% [37] in an earlier study but a more recent study found this to be at 4% [1]. 4. Conclusion Post-operative JET is usually self limited. The sequential use of amiodarone, atrial pacing and surface cooling has improved the outcome of patients with post-operative JET. The intraoperative use of prophylactic amiodarone, magnesium and pre-operative use of propranolol are newer options in management of post-operative JET. Rescue therapy with ablation or extracorporeal membrane oxygenation is an option in postoperative JET but rarely warranted. In contrast, congenital JET is usually Table 3 Management of congenital JET. Study Type of study Age (years) Number of patients Intervention Effective Collins et al. (2009) [1] Multicenter retrospective Fetus Amiodarone 60% (with other antiarrhythmics) 31% (single agent) Collins et al. (2009) [1] Multicenter retrospective Radiofrequency 82% Collins et al. (2009) [1] Multicenter retrospective Cryoablation 85% Law et al. (2006) [38] Retrospective Cryoablation 83% Emmel et al. (2011) [39] Retrospective Cryoablation 90% Numan et al. (2010) [40] Retrospective Neonates 4 Cryoablation 100% Brugada et al. (2010) [41] Retrospective Neonate 1 Radiofrequency Success

6 54 A.S. Batra, N. Mohari / Progress in Pediatric Cardiology 35 (2013) incessant, and management with pharmacotherapy and ablation is more commonly warranted. References [1] Collins KK, Van Hare GF, Kertesz NJ, et al. Pediatric nonpost-operative junctional ectopic tachycardia medical management and interventional therapies. J Am Coll Cardiol 2009;24(53): [2] Gebauer RA, Paech C, Kolterer B, Daehnert I, Kostelka M. Postoperative junctional ectopic tachycardia. Clin Res Cardiol 2011;100:857-8 (abstr). [3] Mildh L, Hiippala A, Rautiainen P, Pettilä V, Sairanen H, Happonen JM. Junctional ectopic tachycardia after surgery for congenital heart disease: incidence, risk factors and outcome. Eur J Cardiothorac Surg 2011;39: [4] Smith AH, Owen J, Borgman KY, Fish FA, Kannankeril PJ. Relation of milrinone after surgery for congenital heart disease to significant postoperative tachyarrhythmias. Am J Cardiol 2011;108: [5] Andreasen JB, Johnsen SP, Ravn HB. Junctional ectopic tachycardia after surgery for congenital heart disease in children. Intensive Care Med 2008;34: [6] Chaiyarak K, Soongswang J, Durongpisitkul K, et al. Arrhythmia in early post cardiac surgery in pediatrics: Siriraj experience. J Med Assoc Thai 2008;91: [7] 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;27:51-5. [8] Delaney JW, Moltedo JM, Dziura JD, Kopf GS, Snyder CS. Early postoperative arrhythmias after pediatric cardiac surgery. J Thorac Cardiovasc Surg 2006;131: [9] Hoffman TM, Bush DM, Wernovsky G, et al. Postoperative junctional ectopic tachycardia in children: incidence, risk factors, and treatment. Ann Thorac Surg 2002;74: [10] Dodge-Khatami A, Miller OI, Anderson RH, et al. Impact of junctional ectopic tachycardia on postoperative morbidity following repair of congenital heart defects. Eur J Cardiothorac Surg 2002;21: [11] Dan P. Post-ischemic effect of dopamine on pacemaker automaticity is age- and tissue-specific: a potential mechanism of junctional ectopic tachycardia (JET). Can J Cardiol 2011;27(Suppl. 1):S291 (abstr). [12] Ye Sheng X, Qu Y, Dan P, et al. Isolation and characterization of atrioventricular nodal cells from neonate rabbit heart. Circ Arrhythm Electrophysiol 2011;4: [13] Chelu MG, Sarma S, Sood S, et al. Calmodulin kinase II-mediated sarcoplasmic reticulum Ca 2+ leak promotes atrial fibrillation in mice. J Clin Invest 2009;119: [14] El-Armouche A, Boknik P, Eschenhagen T, et al. Molecular determinants of altered Ca 2+ handling in human chronic atrial fibrillation. Circulation 2006;114: [15] 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: [16] Kamel YH, Sewielam M. Arrhythmias as early post-operative complications of cardiac surgery in children at Cairo University. J Med Sci 2009;9: [17] Cuenca Peiró V, Pérez Villardón B, Zabala Arguelles JI, et al. Junctional ectopic tachycardia in congenital heart disease: not a rare complication. Intensive Care Med 2011;37(Suppl. 1):S177 (abstr). [18] Mahmoud AB, Tantawy AE, Kouatli AA, Baslaim GM. Propranolol: a new indication for an old drug in preventing postoperative junctional ectopictachycardia after surgical repair of tetralogy of Fallot. Interact Cardiovasc Thorac Surg 2008;7: [19] Niu M, Decker JA, Cannon BC, et al. The infundibulum sparing repair of tetralogy of Fallot is associated with an extremely low incidence of arrhythmias. Heart Rhythm 2010;7:5(Suppl. 1):S313 (abstr). [20] Borgman KY, Smith AH, Owen JP, Fish FA, Kannankeril PJ. A genetic contribution to risk for postoperative junctional ectopic tachycardia in children undergoing surgery for congenital heart disease. Heart Rhythm 2011;8: [21] Haas NA, Plumpton K, Justo R, Jalali H, Pohlner P. Postoperative junctional ectopic tachycardia (JET). Z Kardiol 2004;93: [22] Kovacikova L, Hakacova N, Dobos D, Skrak P, Zahorec M. Amiodarone as a first-line therapy for postoperative junctional ectopic tachycardia. Ann Thorac Surg 2009;88: [23] Plumpton K, Justo R, Haas N. Amiodarone for post-operative junctional ectopic tachycardia. Cardiol Young Feb. 2005;15(1):13-8. [24] Imamura M, Dossey AM, Garcia X, Shinkawa T, Jaquiss RD. Prophylactic amiodarone reduces junctional ectopic tachycardia after tetralogy of Fallot repair. J Thorac Cardiovasc Surg 2012;143: [25] Manrique AM, Arroyo M, Lin Y, et al. Magnesium supplementation during cardiopulmonary bypass to prevent junctional ectopic tachycardia after pediatric cardiac surgery: a randomized controlled study. J Thorac Cardiovasc Surg 2010;139: [26] Mandapati R, Byrum CJ, Kavey RE, et al. Procainamide for rate control of postsurgical junctional tachycardia. Pediatr Cardiol 2000;21: [27] Bronzetti G, Formigari R, Giardini A, Frascaroli G, Gargiulo G, Picchio FM. Intravenous flecainide for the treatment of junctional ectopic tachycardia after surgery for congenital heart disease. Ann Thorac Surg 2003;76: [28] Paul T, Reimer A, Janousek J, Kallfelz HC. Efficacy and safety of propafenone in congenital junctional ectopic tachycardia. J Am Coll Cardiol 1992;20: [29] Chrysostomou C, Beerman L, Shiderly D, Berry D, Morell VO, Munoz R. Dexmedetomidine: a novel drug for the treatment of atrial and junctional tachyarrhythmias during the perioperative period for congenital cardiac surgery: a preliminary study. Anesth Analg 2008;107: [30] BashSE,ShahJJ,AlbersWH,GeissDM.Hypothermiaforthetreatmentofpostsurgical greatly accelerated junctional ectopic tachycardia. J Am Coll Cardiol 1987;10: [31] Kelly BP, Gajarski RJ, Ohye RG, Charpie JR. Intravenous induction of therapeutic hypothermia in the management of junctional ectopic tachycardia: a pilot study. Pediatr Cardiol 2010;31:11-7. [32] Janousek J, Vojtovic P, Gebauer RA. Use of a modified, commercially available temporary pacemaker for R wave synchronized atrial pacing in postoperative junctional ectopic tachycardia. Pacing Clin Electrophysiol 2003;26: [33] Tsoutsinos AJ, Papagiannis J, Chatzis AC, Sarris G. Surgical cryoablation for lifethreatening postoperative junctional tachycardia. Ann Thorac Surg 2007;84: [34] Braunstein Jr PW, Sade RM, Gillette PC. Life-threatening postoperative junctional ectopic tachycardia. Ann Thorac Surg 1992;53: [35] Dyamenahalli U, Tuzcu V, Fontenot E, et al. Extracorporeal membrane oxygenation support for intractable primary arrhythmias and complete congenital heart block in newborns and infants: short-term and medium-term outcomes. Pediatr Crit Care Med 2012;13: [36] Darst JR, Kaufman J. Case report: an infant with congenital junctional ectopic tachycardia requiring extracorporeal mechanical oxygenation. Curr Opin Pediatr 2007;19: [37] Villain E, Vetter VL, Garcia JM, Herre J, Cifarelli A, Garson Jr A. Evolving concepts in the management of congenital junctional ectopic tachycardia. A multicenter study. Circulation 1990;81: [38] Law IH, Von Bergen NH, Gingerich JC, Saarel EV, Fischbach PS, Dick II M. Transcatheter cryothermal ablation of junctional ectopic tachycardia in the normal heart. Heart Rhythm 2006;3: [39] Emmel M, Sreeram N, Khalil M, Brockmeier K. Cryoenergy for the ablation of arrhythmogenic paraseptal substrates in children and adolescents with heart rhythm disorders. Dtsch Med Wochenschr 2011;136: [Article in German]. [40] Numan MT, Mahmud E. Cryo ablation of congenital junctional ectopic tachycardia with medium term follow-up. Cardiol Young 2010;20(Suppl. 1):141 (abstr). [41] Brugada G, Bartrons J, Jimenez L, et al. Drug-refractory arrhythmias: radiofrequency ablation in neonates. Cardiol Young 2010;20(Suppl. 2):S49-50 (abstr). [42] Tulino D, Dattilo G, Tulino V, Marte F, Patanè S. A congenital form of junctional ectopic tachycardia. Int J Cardiol Nov ;145(2):e54-6. [43] Dubin AM, Cuneo BF, Strasburger JF, Wakai RT, Van Hare GF, Rosenthal DN. Congenital junctional ectopic tachycardia and congenital complete atrioventricular block: a shared etiology? Heart Rhythm 2005;2: [44] Cuneo BF, Strasburger JF, Wakai RT. Magnetocardiography in the evaluation of fetuses at risk for sudden cardiac death before birth. J Electrocardiol 2008;41(116): e1-6. [45] Benjamín MN, Infante J, Olmedo J, Abello M, Moltedo JM. Congenital junctional ectopic tachycardia. Pharmacologic management during infancy. Medicina 2011;71: