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CLINICAL RESEARCH: HEART RHYTHM DISORDERS IN CHILDREN

Pediatric Nonpost-Operative Junctional Ectopic Tachycardia

Medical Management and Interventional Therapies

Kathryn K. Collins, MD, FACC^_*,_*, George F. Van Hare, MD, FACC^,,, Naomi J. Kertesz, MD, FACC, Ian H. Law, MD, FACC^||, Yaniv Bar-Cohen, MD, FACC^¶, Anne M. Dubin, MD, FACC, Susan P. Etheridge, MD, FACC^#, Charles I. Berul, MD, FACC^_**, Jennifer N. Avari, MD, Volkan Tuzcu, MD, Narayanswami Sreeram, MD, Michael S. Schaffer, MD^_*, Anne Fournier, MD, FACC^||||, Shubhayan Sanatani, MD^¶¶, Christopher S. Snyder, MD^##, Richard T. Smith, Jr, MD, FACC^_***, Luis Arabia, MD, Robert Hamilton, MD, Terrence Chun, MD, Leonardo Liberman, MD^||||||, Bahram Kakavand, MD, FACC^¶¶¶, Thomas Paul, MD, FACC^### and Ronn E. Tanel, MD^_****

^_* Departments of Pediatrics, Divisions of Cardiology, The Children's Hospital, Denver, Colorado
Departments of Pediatrics, Divisions of Cardiology, University of California, San Francisco, California
Departments of Pediatrics, Divisions of Cardiology, Stanford University, Palo Alto, California
Departments of Pediatrics, Divisions of Cardiology, Texas Children's Hospital, Houston, Texas
^|| Departments of Pediatrics, Divisions of Cardiology, University of Iowa Children's Hospital, Iowa City, Iowa
^¶ Departments of Pediatrics, Divisions of Cardiology, Children's Hospital, Los Angeles, California
^# Departments of Pediatrics, Divisions of Cardiology, Primary Children's Hospital, Salt Lake City, Utah
^_** Departments of Pediatrics, Divisions of Cardiology, Children's Hospital, Boston, Massachusetts
Departments of Pediatrics, Divisions of Cardiology, Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, Missouri
Departments of Pediatrics, Divisions of Cardiology, Arkansas Children's Hospital, Little Rock, Arkansas
Departments of Pediatrics, Divisions of Cardiology, University Hospital of Cologne, Koln, Germany
^|||| Departments of Pediatrics, Divisions of Cardiology, Hospital Sainte-Justine, Montreal, Quebec, Canada
^¶¶ Departments of Pediatrics, Divisions of Cardiology, British Columbia Children's Hospital, Vancouver, British Columbia, Canada
^## Departments of Pediatrics, Divisions of Cardiology, Ochsner Children's Hospital, New Orleans, Louisiana
^_*** Departments of Pediatrics, Divisions of Cardiology, Sanger Clinic, Charlotte, North Carolina
Departments of Pediatrics, Divisions of Cardiology, Sanatorio del Salvador, Argüello, Cordoba, Argentina
Departments of Pediatrics, Divisions of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada
Departments of Pediatrics, Divisions of Cardiology, Children's Heart Center, Seattle, Washington
^|||||| Departments of Pediatrics, Divisions of Cardiology, Children's Hospital of New York-Presbyterian, New York, New York
^¶¶¶ Departments of Pediatrics, Divisions of Cardiology, University of Kentucky, Lexington, Kentucky
^### Departments of Pediatrics, Divisions of Cardiology, Georg-August-University, Göttingen, Germany
^_**** Departments of Pediatrics, Divisions of Cardiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Manuscript received August 4, 2008; revised manuscript received November 12, 2008, accepted November 16, 2008.

^_* Reprint requests and correspondence: Dr. Kathryn K. Collins, The Children's Hospital, Section of Cardiology/B100, 13123 E. 16th Avenue, Aurora, Colorado 80045 (Email: Collins.kathryn{at}tchden.org).

	Abstract

Top Abstract Methods Results Discussion Conclusions References

 
Objectives: To determine the outcomes of medical management, pacing, and catheter ablation for the treatment of nonpost-operative junctional ectopic tachycardia (JET) in a pediatric population.

Background: Nonpost-operative JET is a rare tachyarrhythmia that is associated with a high rate of morbidity and mortality. Most reports of clinical outcomes were published before the routine use of amiodarone or ablation therapies.

Methods: This is an international, multicenter retrospective outcome study of pediatric patients treated for nonpost-operative JET.

Results: A total of 94 patients with JET and 5 patients with accelerated junctional rhythm (age 0.8 year, range fetus to 16 years) from 22 institutions were identified. JET patients presenting at age 6 months were more likely to have incessant JET and to have faster JET rates. Antiarrhythmic medications were utilized in a majority of JET patients (89%), and of those, amiodarone was the most commonly reported effective agent (60%). Radiofrequency ablation was conducted in 17 patients and cryoablation in 27, with comparable success rates (82% radiofrequency vs. 85% cryoablation, p = 1.0). Atrioventricular junction ablation was required in 3% and pacemaker implantation in 14%. There were 4 (4%) deaths, all in patients presenting at age 6 months.

Conclusions: Patients with nonpost-operative JET have a wide range of clinical presentations, with younger patients demonstrating higher morbidity and mortality. With current medical, ablative, and device therapies, the majority of patients have a good clinical outcome.

Key Words: junctional ectopic tachycardia • arrhythmia • amiodarone • radiofrequency catheter ablation • cryoablation • child

Abbreviations and Acronyms   AJR = accelerated junctional rhythm   JET = junctional ectopic tachycardia   RF = radiofrequency

The purpose of this study is to describe outcomes of pediatric patients treated for JET, specifically addressing efficacy and safety of medical management, pacing, and catheter ablation.

	Methods

Top Abstract Methods Results Discussion Conclusions References

 
Patient population.   This is an international, multicenter retrospective review of nonpost-operative junctional tachycardias from the Pediatric and Congenital Electrophysiology Society. Approval for medical chart review was obtained from the Institutional Review Board at each institution. All patients 18 years of age evaluated and treated with the diagnosis of nonpost-operative JET or accelerated junctional rhythm (AJR) were included. Patients had either a normal structural heart or only minor cardiac defects that did not require cardiac surgery.

The diagnosis of JET was based on clinical, noninvasive evaluation of the patient by the attending electrophysiologist, using established electrocardiographic criteria (1,5) in addition to JET rate criteria (23,24). JET was defined as a tachycardia originating from the atrioventricular junction with gradual onset, gradual offset, and rate variability. The following features were observed: 1) a narrow QRS complex with either atrioventricular dissociation and sinus capture beats or 1:1 V:A association; or 2) a wide QRS complex with atrioventricular dissociation and sinus capture beats with the same wide QRS complex noted during tachycardia, the sinus capture beats, or sinus rhythm. JET was further defined by a junctional rate >95th percentile of heart rate for age (23,24). Patients with junctional rates 95th percentile were reported as having AJR. JET frequency on presentation was classified as incessant (a consistent tachycardia without conversion to sinus rhythm), sustained (JET occurring >50% of the time), or sporadic (predominantly sinus rhythm with episodic JET).

Data collection.   Medical charts were reviewed for the following: age at presentation, symptoms, family history of JET, antiarrhythmic therapies, details of radiofrequency (RF), or cryoablation procedures, the placement of a permanent pacemaker or defibrillator, and clinical outcomes. The finding of spontaneous atrioventricular block was recorded (10).

Statistical analysis.   Data are presented as median (range). Chi-square and Fisher exact tests were utilized for categorical variables. The Wilcoxon rank sum test was used for nonparametric comparisons of continuous variables. Linear regression was utilized for the evaluation of JET rate as a function of patient age.

	Results

Top Abstract Methods Results Discussion Conclusions References

 
Patient population.   The study population consisted of 94 patients with JET and 5 patients with AJR from 22 institutions (Table 1). Several patients have been described previously (8,9,14,17,21). The median year of presentation was 2001 (1969 to 2008), with only 6 patients presenting before the availability of RF ablation. A familial association was noted in 20% of patients. The presence of maternal lupus antibodies was not routinely evaluated; however, 1 mother was known to be anti-Rho and anti-La positive. Minor heart defects were diagnosed in 24%, including 16 patent foramen ovale, 1 muscular ventricular septal defect, 4 patent ductus arteriosis, and 3 mitral valve prolapse.

Patients with JET.   Patient age on presentation of JET was almost evenly divided between 6 months of life and >6 months of life (Table 1). Symptoms on presentation varied (Fig. 1). The majority of patients (60%; 56 of 94) had a rapid or irregular heart rate sensed by the patient or evaluated on physical examination. 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.

View larger version (16K): [in this window] [in a new window] [Download PPT slide]   Figure 1 Presenting Signs or Symptoms for Nonpost-Operative Junctional Ectopic Tachycardia The presenting signs or symptoms are shown for 94 pediatric patients with nonpost-operative junctional ectopic tachycardia. Blue = rapid or irregular heart rate; red = heart failure; orange = fetal tachycardia with hydrops; yellow = fetal tachycardia without hydrops; pink = screening electrocardiogram; lavender = syncope.

View larger version (17K): [in this window] [in a new window] [Download PPT slide]   Figure 2 Frequency of JET on Presentation This graph depicts the number of patients with incessant, sporadic, and episodic junctional ectopic tachycardia (JET). The bars are further divided by age at presentation of 6 months (blue area) and >6 months (pink area). Patients who were age 6 months were more likely to have incessant JET, whereas patients age >6 months were more likely to have episodic JET (p < 0.0001).

View larger version (8K): [in this window] [in a new window] [Download PPT slide]   Figure 3 JET Rate on Presentation as Function of Patient Age This graph shows the relationship of junctional ectopic tachycardia (JET) rate (beats/min) on presentation with the patient's age (years) at presentation. Patients who presented at a younger age had higher JET rates (r2 = 0.232, p < 0.0001).

A wide variety of antiarrhythmic medications was utilized (Table 2). The majority of patients (62%; 52 of 84) required concomitant administration of 2 antiarrhythmic medications. Medications resulted in complete suppression of JET in only 11% (9 of 84). More commonly, medications were associated with a decrease in JET rate or frequency in 70% (59 of 84). In the remaining 19% (16 of 84), medications had no effect. Of the antiarrhythmic agents reported as successfully affecting the rate or frequency of JET, amiodarone alone or in combination was the most frequently cited medication, at 60% (41 of 68) (Table 3).

Data comparing RF ablation to cryoablation reflect information for the first ablation procedure performed at the institution. In the cryoablation group, the 1 patient with AJR and cryoablation is also included in the analysis (Table 4). The indication for ablation was largely heart failure or refractory JET for patients undergoing RF ablation and elective for those undergoing cryoablation. A 3-dimensional mapping system was utilized in 4 patients with cryoablation. Radiofrequency or cryoablation lesions were placed during sinus or atrial-paced rhythm in approximately one-third of the patients and in JET for two-thirds. Cryoablation catheter tip size was evenly divided between a 4- and 6-mm tip. A freeze-thaw-freeze was utilized in 7 patients.

Permanent pacemakers in patients with JET.   Permanent pacing systems were placed in 14% (13 of 94) patients. Complete atrioventricular block was the indication for pacing in 10 patients: 3 subsequent to ablation of the atrioventricular junction, 4 secondary to inadvertent atrioventricular block during RF ablation with their initial or subsequent procedure, and 3 with spontaneous atrioventricular block. The remaining 3 patients had a placement of a permanent pacemaker for the following indications: 1 had a pacemaker implanted at age 5 weeks for "back-up" pacing, and this was explanted 10 years later; 1 had sinus bradycardia on antiarrhythmic therapy; and 1 had a possible asystolic cardiac arrest.

Comorbidities and complications in patients with JET.   Comorbidities or complications were reported for 13 patients during their treatment for JET and none for patients with AJR (Table 5). One of the patients had sustained a cardiac arrest and had an implantable cardioverter-defibrillator placed at age 9 years; this was a patient with possible myocarditis.

Twenty patients (21%) continued antiarrhythmic therapy, but with simplification of their medical regimens. Patients remained on regimens of amiodarone (n = 7), amiodarone plus beta-blocker (n = 2), amiodarone plus flecainide (n = 1), beta-blocker (n = 4), digoxin (n = 3), beta-blocker plus digoxin (n = 2), flecainide plus digoxin (n = 1), and propafenone plus digoxin (n = 1).

Deaths.   Death occurred in 4 (4%) patients, all of whom presented with JET at age 6 months. The presenting JET rate was 205 to 270 beats/ min. Two infants died at 1 week of age after presenting with fetal tachycardia and hydrops. A third patient died at age 11 months with complications from heart failure. The fourth infant died suddenly at age 7 months. After a prenatal diagnosis, his JET rate was well controlled on amiodarone and digoxin. Laboratory evaluation indicated hypocalcemia and vitamin D deficiency rickets, for which he was being treated. His sudden death suggested the possibility that electrolyte imbalances in addition to the antiarrhythmic medications could have provoked an acute lethal arrhythmia.

	Discussion

Top Abstract Methods Results Discussion Conclusions References

 
This international multicenter study documents the outcomes of 94 pediatric patients with nonpost-operative JET and 5 patients with AJR. To our knowledge, this is the largest published series that reflects the current era management strategies for this problem. As in previous smaller series, JET continues to be difficult to treat. Patient outcomes, however, have improved with medical management (primarily amiodarone), permanent pacing, RF ablation, and cryoablation. Interventions such as ablation of the atrioventricular junction were required less frequently than in prior reports.

Definition of JET versus AJR.   The mechanism of JET is thought to be an automatic focus originating at or near the atrioventricular junction. Junctional rates can be quite variable, and range from AJR to the more rapid JET. In review of prior literature pertaining to nonpost-operative JET, there appears to be no specific heart rate cut-off for the diagnosis of AJR versus JET (3–5,14,17). In creating a precise definition of JET for this manuscript, a survey of the authors was conducted with 3 proposed definitions for JET versus AJR based on prior studies in similar but different tachyarrhythmias: 1) JET defined by a junctional rate >95th percentile of heart rate for age; this definition was utilized in a study of the efficacy of amiodarone in a largely post-operative congenital heart disease population (24); 2) JET defined by a junctional rate of >170 beats/min; this definition was utilized in a study evaluating the treatment of JET in the post-operative congenital heart disease population (25); or 3) JET defined by >10% to 20% of the surrounding sinus heart rate; this type of definition was utilized to differentiate accelerated ventricular rhythm from ventricular tachycardia (26). Ultimately, the authors agreed upon the definition of JET that included >95th percentile of heart rate because it factored in both tachycardia rate and patient age and also had clinical significance, with patients having AJR likely being less affected than those with JET.

Clinical outcomes comparison with prior reports.   The largest prior report of nonpost-operative JET was published by Villain et al. (5) and described 26 infants with JET between 1970 and 1987. In that article, atrioventricular junction ablation was performed in 23%, pacemakers were placed in 15%, and death occurred in 35%. In comparison, our patients had improved clinical courses, with atrioventricular junction ablation performed in only 3%, a similar number of pacemaker placements at 14%, and a lower risk of death at 4%. There are, however, several differences in the patient populations. In the prior study (5), only infants age 6 months were included. Of these, 61% had decreased ventricular function and congestive heart failure. Secondary to the different eras of the studies, none of the patients in that study had RF or cryoablation for JET. Also, several of the atrioventricular junction ablations were completed surgically. In the present study, we included all patients 18 years of age who were diagnosed with JET. Only 20% presented with decreased ventricular function or hydrops secondary to fetal tachycardia.

Consistent with the study by Villian et al. (5) is the findings that patients who present at age 6 months are more likely to have incessant JET and faster JET rates. These youngest patients were also more likely to have associated comorbidities and a higher risk of death. At last follow-up, 75% of the patients in the current study were doing well on no medications for JET. This outcome is primarily due to ablative therapies, but also includes cases of spontaneous remission and patients in whom the JET persists at a slower rate that is not causing clinical symptoms or hemodynamic compromise. A smaller case series (3) reported 9 patients with JET, all of whom presented at age 6 months with incessant JET and were able to be medically managed. Despite a long follow-up period of 3 to 21 years, none was able to be weaned from medications. While there may be some differences in patient population between the prior studies and ours, the differences in outcomes may likely be due to the more widespread use of amiodarone and the advancement in ablative technologies.

Antiarrhythmic medications.   Reflecting the difficulties in treating JET and the multicenter nature of the present study, patients were prescribed a variety of antiarrhythmic therapies. Many patients required >2 medications, either sequentially or in combination, to eventually see a salutary drug effect on JET rate. As in prior studies, our findings support the use of amiodarone for the treatment of JET (3,5). For patients for whom medications were thought to be effective for tachycardia conversion or rate control, amiodarone was the most frequently cited medication. Still, many patients required amiodarone in combination with a second agent.

Ablation.   The first reported RF catheter ablation in a child was in 1990 (21), in a patient with JET who had an initial successful ablation but required subsequent atrioventricular junction ablation. Subsequently, other case reports have shown successful ablation of JET with preservation of atrioventricular nodal conduction (2,8,11–13,18–21,27,28). With radiofrequency ablation in close proximity to the normal conduction system, however, there remains a significant risk of complete atrioventricular block, which would require the placement of a permanent pacing system. In the multicenter Prospective Assessment After Pediatric Cardiac Ablation study (29), only 9 cases of RF ablation of JET were reported in the "not cohort-eligible" registry. In these patients, there was a 100% success rate and an 11% rate of atrioventricular block. By comparison, in the present study, 17 patients underwent RF ablation for JET, with an initial success rate of 82% and a risk of inadvertent atrioventricular block of 18% (3 of 17).

In the early 2000s, catheter cryoablation became available as an alternative energy source to RF ablation. Cryoablation has specific advantages of increased safety when used near the normal conduction system. Previously, cryoablation of JET has been reported in 8 pediatric patients (14,17,30), with an initial success rate of 100% and no reported inadvertent atrioventricular block. In the present study, 27 patients have undergone cryoablation procedures for JET. When compared with RF ablation, cryoablation was more likely to be an elective procedure in patients with sporadic or sustained JET. Cryoablation resulted in an initial success rate of 85%, with no atrioventricular block. The recurrence rate for both RF ablation and cryoablation of JET were similar at 13% to 14%.

Intentional atrioventricular junction ablation was performed infrequently in our JET population. Only 3 patients underwent this treatment, and these were earlier in the study. Unlike prior reports of JET therapy, the atrioventricular junction ablations were carried out with a transcatheter technique.

The patients in the present report appeared to benefit significantly from ablation procedures. While the choice between RF ablation and cryoablation should be at the discretion of the electrophysiologist, it seems prudent to err on the side of safety with cryoablation technology.

Pacemakers and atrioventricular block.   A total of 14% of patients in the present study required permanent pacemakers. This outcome is similar to that in the 1990 study by Villain et al. (5). In our patients, the indication for pacing was largely atrioventricular block secondary to RF ablation of JET or atrioventricular junction ablation. Only a few patients had spontaneous atrioventricular block. Dubin et al. (10) described a possible association between congenital JET and congenital atrioventricular block with anti-Ro and anti-La antibodies in the mother. In our population, the history of maternal lupus or maternal anti-lupus antibodies was largely unknown.

Deaths.   The mortality rate for JET has been previously reported by Villain et al. (5) to be 34%, with 2 of 9 being sudden unexplained deaths in infants thought to have the JET rate controlled with medications. In contrast, Cilliers et al. (3) showed no deaths among 9 patients with JET. In our population, we report a 4% mortality; all deaths occurred among patients presenting at age 6 months. Only 1 death was sudden and may have been secondary to possible electrolyte imbalances in a patient being treated with antiarrhythmic agents.

Study limitations.   This was a retrospective review, with associated biases of retrospective studies. Among the 22 institutions, there was no standard approach to JET management. With medical management, the dose and duration of therapies were not specifically recorded.

	Conclusions

Top Abstract Methods Results Discussion Conclusions References

 
This international multicenter study of nonpost-operative JET in pediatric patients demonstrates improved outcomes with the current available therapies of medical management (primarily amiodarone), permanent pacing, RF ablation, and cryoablation.

	Acknowledgments

 
The authors would like to thank the following for assistance with data collection: Nancy Chiesa, RN, Derek Patton, Nichols H. Von Bergen, MD, Maureen Brinkman, RN, Mark D. Levin, MD, Cristina Otino, MD, and Felipe Somoza, MD.

	Footnotes

 
Dr. Collins is a speaker for St. Jude Medical. Dr. Dubin receives fellowship support from Medtronic. Dr. Berul is a consultant for Johnson & Johnson and Novartis. Dr. Tuzcu is a consultant for St. Jude Medical. Dr. Santani has received an unrestricted grant for research from Medtronic. Dr. Law is a speaker for Cryocath.

	References

Top Abstract Methods Results Discussion Conclusions References

 
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