Author + information
- Received December 29, 2017
- Revision received February 12, 2018
- Accepted February 22, 2018
- Published online April 16, 2018.
- David Backhoff, MD∗ (, )
- Sophia Klehs, MD,
- Matthias J. Müller, MD,
- Heike E. Schneider, MD,
- Jana-Katharina Dieks, MD,
- Thomas Paul, MD and
- Ulrich Krause, MD
- Department of Pediatric Cardiology and Intensive Care Medicine, Georg August University Medical Center, Göttingen, Germany
- ↵∗Address for correspondence:
Dr. David Backhoff, Department of Pediatric Cardiology and Intensive Care Medicine, Georg August University, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany.
Objectives The purpose of this study was to evaluate long-term safety and efficacy of catheter ablation of accessory atrioventricular pathways (AP) in a pediatric cohort.
Background Radiofrequency catheter ablation of accessory AP is the recommended treatment for patients with atrioventricular re-entrant tachycardia. Data on long-term results ≥1 year after AP ablation in pediatric patients is sparse.
Methods A total of 296 patients <18 years of age who had undergone radiofrequency-AP ablation between October 2002 and June 2015 were included into the study. Follow-up was >1 year in all patients. Median age at ablation had been 11.6 years, and median follow-up was 5.6 years. Recurrence of AP conduction after ablation was defined as documentation of pre-excitation, supraventricular tachycardia attributable to AP, or proof of AP conduction during repeat electrophysiological study.
Results AP ablation succeeded in 268 of 296 individuals (91%). After successful ablation, recurrence of AP conduction was observed in 29 of 268 individuals (10.8%). Of those 29, 23 (79%) had AP recurrence within the first year after ablation, whereas 13 (45%) had recurrence of AP conduction already within the first month. Six patients had late recurrence of AP conduction >1 year post-ablation. Procedural success and freedom from AP conduction after a single ablation procedure was 86% at 1 month, 83% at 1 year, and 81% at 5 years after ablation.
Conclusions After radiofrequency ablation of AP in children, recurrence of AP conduction occurred in 23 subjects (8% of the study cohort) within the first year after ablation. Late recurrences >1 year after ablation were noticed in 6 children (2% of the study group), highlighting the need for longer follow-up >1 year. Results of the present study on late AP recurrence should be taken into account whenever families are counselled for pediatric AP ablation.
Catheter ablation of accessory atrioventricular pathways (AP) is the recommended treatment for children and adolescents with atrioventricular re-entrant tachycardia (AVRT) as well as for those with asymptomatic pre-excitation in case of short AP anterograde refractory periods (1,2). Data on efficacy and safety of pediatric catheter ablation using radiofrequency (RF) was reported more than 20 years ago by the North American Pediatric Electrophysiology Society multicenter registry (3–6). Recent analysis of pediatric cohorts including up to 600 patients have demonstrated improved success and low complication rates by use of state of the art techniques such as 3-dimensional mapping and navigation systems (7,8) and the availability of cryogenic energy as an alternative energy source (2). However, almost all studies on catheter ablation in children have reported on procedural success and on follow-up after successful ablation separately (5,8). Moreover, data focusing on follow-up after catheter ablation is mainly limited to the first year following ablation (5,7,8). At the present time, there is a lack of data on long-term efficacy in terms of a combined endpoint including primary success and recurrence, which is of paramount concern for families when considering pediatric catheter ablation.
To date, no systematic data is available on long-term fate of children undergoing RF ablation of AP. We therefore analyzed follow-up data of all children who had undergone RF ablation of AP during the last decade at our tertiary pediatric electrophysiology (EP) center.
Special attention was paid to occurrence and timing of reappearance of AP conduction, impact of procedural data, and AP localization, as well as long-term safety concerning development of secondary arrhythmias.
All children and adolescents <18 years of age, who were scheduled for RF catheter ablation of AP between October 1, 2002, and July 31, 2015, at our institution were included in this study. A total of 296 subjects were identified. Procedural data and primary success rates as well as acute complications have recently been published (9). Patients who underwent AP ablation with cryogenic energy or with RF and cryogenic energy combined were excluded from this analysis. Data from patients after initially successful AP ablation were separately assessed from those with ablation failure in order to avoid bias by including follow-up data of repeat procedures.
Recurrence >1 year after ablation was defined as late recurrence. Congenital heart defects (CHD) were considered exclusively in case of structural abnormalities relevant for catheter ablation. Patients with repaired CHD and normal intracardiac anatomy (i.e., patients after surgical or catheter-guided closure of atrial or ventricular septal defects, closure of arterial ductus, status post balloon valvuloplasty of aortic/pulmonic stenosis) were not considered to have CHD relevant to this study.
The study was approved by the institutional review board and fully complies with the Declaration of Helsinki. Informed consent was obtained from the patients and/or their parents/legal guardians, respectively.
The institutional approach for EP study and RF ablation has been described before (9). In general, a total of 3 diagnostic EP catheters were placed within the coronary sinus, at the His bundle, and within the apex of the right ventricle. In selected patients with a body weight <15 kg, the number of catheters was reduced by recording His bundle signals from the proximal electrodes of a decapolar electrode catheter and using the distal electrodes of the same catheter for right ventricular pacing and recording. In selected patients, a transesophageal probe served as reference for left atrial activation. In all patients, catheter navigation and endocardial mapping were guided by 3-dimensional nonfluoroscopic catheter navigation systems (LocaLisa, Medtronic EP Systems, Minneapolis, Minnesota; EnSite NavX, St. Jude Medical, St. Paul, Minnesota). Mapping and ablation was performed with a standard 5-F (body weight ≤25 kg) or a standard 7-F (body weight >25 kg) nonirrigated catheter with a 4-mm tip. For access to the left atrium, a transfemoral, transseptal approach was used in all patients. In the case of overt pre-excitation, unipolar signals from the tip of the ablation catheter were used in addition to bipolar signals to aid localization of the AP. In patients with concealed AP, AP mapping was performed by right ventricular pacing or during orthodromic AVRT. In patients with body weight >25 kg, RF ablation was performed in a temperature-controlled mode with the generator output set to 30 to 50 W and a target temperature of 65°C. In patients with body weight ≤25 kg, maximum generator power output was 30 W with a target temperature of 65°C. If AP conduction remained present after 15 s of ablation, energy delivery was stopped and mapping was continued. If AP conduction was interrupted within 15 s of RF energy application, energy application was continued for a total of 30 s at this spot. Primary procedural endpoint was interruption of retrograde and (in case of overt pre-excitation) anterograde AP conduction during ablation. Additional “insurance applications” were not applied in small children (i.e., body weight <15 kg), in patients with AP in close anatomical proximity to the normal conduction system, and in patients with posteroseptal AP in close proximity to the left circumflex coronary artery. In the remaining patients, 1 to 2 “insurance applications” were applied at the discretion of the operator with the same RF generator settings for 30 s. Procedures were concluded after a waiting period of 30 min and repeated proof of AP ablation.
All patients had an electrocardiogram (ECG) and Holter monitoring following the ablation procedure. 2D echocardiography was performed to rule out pericardial effusion. After discharge from hospital patients were seen in our outpatient clinics after 4 weeks and on annual basis subsequently. Subjects referred for ablation (216 of 296; 73%) were reevaluated by their primary cardiologist. An ECG was performed at each of the follow-up visits. Follow-up data were gathered from our institutional records and from questionnaires sent to the families as well as to the referring cardiologists, respectively. Recurrence of AP conduction was defined as recurrence of ventricular pre-excitation on ECG, recurrence of supraventricular tachycardia (SVT) or presence of AP conduction during repeat EP study in patients with symptoms attributable to SVT and failed SVT documentation. All patients had a follow-up of ≥1 year.
Statistical analysis was performed using SPSS 24.0 software (IBM, Armonk, New York). Numerical data are presented as median (interquartile range [IQR]). To assess freedom from AP conduction, the Kaplan-Meier method was used with time of AP ablation set as 0. Patients in whom ablation had failed were included into this analysis but were censored at the time of ablation (0). Therefore, Kaplan-Meier curve origin was set below 100%. Individuals exhibiting multiple AP with failure of complete ablation of all AP present were considered as failures. Subjects not experiencing AP recurrence were censored event-free at the time of the last follow-up evaluation. Freedom from AP conduction was calculated separately both for the whole study group (N = 296) and—to analyze recurrence after ablation precisely—for all patients after successful ablation (n = 268) excluding patients with primary ablation failure. Additionally, individuals with structurally normal hearts (n = 276) were analyzed separately. For this calculation, subjects with congenital heart disease as we have defined or with cardiomyopathy were excluded.
In a final analysis (n = 279), cumulative follow-up including a maximum of 2 subsequent ablation procedures was performed to calculate long-term success with respect to reablation procedures. For this analysis, data of patients that were lost in follow-up or that decided deliberately against a repeat ablation were censored. Influence of additional variables on freedom from AP conduction was computed with univariate Cox regression and log-rank test. A value of p < 0.05 was defined as level of statistical significance.
Follow-up data from 296 patients were included in this study. Median age at the time of the procedure had been 11.6 years (IQR: 7.9 to 14.2 years); median body weight had been 43.3 kg (IQR: 28 to 60 kg). Patient characteristics are provided in Table 1. CHD with potential impact on catheter ablation of AP was present in 12 patients (Ebstein anomaly of the tricuspid valve, n = 7; complex CHD, n = 5). Additionally, cardiomyopathy was present in 8 patients (idiopathic dilated cardiomyopathy, n = 3; hypertrophic cardiomyopathy, n = 2; arrhythmia-induced cardiomyopathy, n = 2; arrhythmogenic right ventricular cardiomyopathy, n = 1) and 1 individual had tuberous sclerosis with cardiac involvement.
Follow-up after initial AP ablation—whole study group
AP ablation was attempted in 296 patients. At the first procedure, AP ablation was achieved in 268 patients (91%) (9). Therefore, the origin of the Kaplan-Meier curve was set at 91% (Figure 1). During median follow-up of 5.6 years (IQR: 3.1 to 9.0 years; minimum 1 year), overall long-term freedom from AP conduction was achieved in 239 individuals (80.7%) while recurrence of AP conduction was noted in 29 patients. Recurrence was observed in 1 of 12 patients with CHD and no recurrence was observed among patients with cardiomyopathy. A total of 26 of 29 patients with AP recurrence had SVT following the initial ablation whereas asymptomatic pre-excitation showed recurrence of AP conduction in 3 of 29 subjects. Of those individuals with SVT recurrence, 12 of 26 subjects had pre-excitation on surface ECG while the remaining 14 of 26 had recurrence of concealed AP conduction.
Among subjects with AP recurrence (n = 29), AP conduction recurred between 1 day and 7.3 years following AP ablation. The majority of AP recurrences (23 of 29; 79%) were noted within the first year after ablation while 13 of 29 (45%) of recurrences were documented already within the first month after ablation. AP conduction recurred in 6 of 29 individuals (21%) ≥12 months after the procedure (i.e., “late recurrence”).
Calculated long-term success (successful ablation and freedom from reappearance of AP conduction and/or SVT) was 86% at 1 month, 83% at 1 year, 81% at 3 years, 81% at 5 years, and 80% at 8 years after the initial ablation (Figure 1). Sex, age, body weight, height, and presence of overt pre-excitation prior to ablation as well as presence of CHD or cardiomyopathy had no impact on long-term outcome. A higher number of RF applications, longer procedure duration, and longer fluoroscopy time were associated with an unsuccessful result (Table 1). Based on the lower procedural success rate (9), right-sided or epicardial as well as multiple AP had a significantly inferior long-term outcome (Table 2).
A separate Kaplan-Meier analysis for patients with successful AP ablation (n = 268, excluding 28 subjects with failed AP ablation and therefore starting with 100% at time 0) yielded 95% freedom from AP recurrence at 1 month, 91% at 1 year, 90% at 3 years, 90% at 5 years, and 88% at 8 years following catheter ablation. In this separate analysis, a higher number of RF lesions and longer procedure duration were also weakly associated with AP recurrence (hazard ratio: 1.21 for each 5 RF applications; 95% confidence interval: 1.04 to 1.41; p = 0.032) and 1.07 for each 10 min additional procedure duration (95% confidence interval: 1.02 to 1.12; p = 0.012). In this subanalysis of patients with successful AP ablation (n = 268), AP localization was not associated with recurrence of AP conduction.
Follow-up after initial AP ablation attempt—patients with structurally normal hearts
Subjects with CHD (n = 12) and cardiomyopathy (n = 8) were excluded for this separate Kaplan-Meier analysis. Ablation succeeded in 257 of 276 individuals (93%), which was defined as Kaplan-Meier origin. During follow-up, overall long-term freedom from AP conduction was achieved in 229 of 276 individuals (83%) and recurrence of AP conduction was noted in 28 patients. Therefore, this Kaplan-Meier curve (not depicted) runs almost parallel 2% points below the curve of the whole study cohort: Calculated long-term success (successful ablation and freedom from reappearance of AP conduction and/or SVT) was 89% at 1 month, 85% at 1 year, 83% at 3 years, 83% at 5 years, and 82% at 8 years after the initial ablation.
Patients with late AP recurrence >1 year after successful AP ablation
All patients with late recurrence had undergone ablation of a left-sided AP (n = 6; p = 0.033). From these 6 pathways, 4 were localized within the left lateral region, 1 AP was found to be left posterior, and the remaining patient had a left posteroseptal AP (Table 3). All children experiencing late recurrence were <13 years of age at the time of ablation. There was, however, no significant difference in age between patients with late recurrence and those with recurrence within the first year following ablation (n = 23; p = 0.356) and individuals with long-term success (n = 239; p = 0.307). Among the 6 subjects with late recurrence, overt pre-excitation was present in 3 at the time of recurrence. In 5 of 6 patients with late recurrence, reablation was performed at our institution whereas patient 5 had reablation at another institution.
Cumulative follow-up including 1-repeat ablation procedures
After failed initial AP ablation, 13 of 28 patients underwent a second ablation with success in 10 of 13 patients (77%). Due to close proximity of the AP to the specialized conduction system and slow AP antegrade conduction properties, repeat ablation was abandoned in 2 of 28 individuals. Those 2 patients were censored from further analysis. AP conduction recurred in 1 patient after the second ablation while long-term success was achieved in 9 individuals. The remaining 13 of 28 patients were lost to follow-up.
All 29 patients with recurrence of AP conduction after the initial successful procedure had a repeat ablation performed. Of the 29 repeat procedures, 27 were performed at our center; 2 individuals underwent reablation and subsequent follow-up at another institution (one of them after late recurrence). For those 2 patients, no follow-up information was available, and they were censored from further analysis. Repeat ablation was successful in 26 of 27 patients. No recurrence of AP conduction was observed in 20 of 27 individuals. In 6 of 27 subjects, AP conduction recurred even after the second ablation (Figure 2).
Data from 279 patients were therefore available for a cumulative follow-up analysis including data after 1 reablation procedure (Figure 2). A total of 17 patients were either lost to follow-up (n = 15) or denied reablation; those patients were censored from analysis. Overall long-term success was achieved in 268 of 279 subjects (96%) including patients who had 1 reablation. A total of 11 of 279 individuals (4%) had failed reablation (n = 4) or had recurrence after reablation (n = 7).
Late complications/secondary arrhythmias
Femoral vein thrombosis with consecutive pulmonary embolism occurred in 1 female adolescent 1 week after ablation as reported before (9). No late arrhythmias including late AV block or other complications attributable to the ablation procedure were noted.
Catheter ablation of accessory pathways in children is the recommended treatment strategy in patients with AVRT and those with asymptomatic pre-excitation and rapid anterograde accessory pathway conduction exposing patients to an increased risk of sudden cardiac death (1,2). Acute success rates of 90% to 95% have been described for RF ablation of AP in children and adolescents (4,7,8). Long-term freedom from AP after ablation has been reported ranging from 78% (5,7) to 93% (8). The present study reports on the results of all subjects scheduled for AP ablation with RF exclusively at a tertiary pediatric EP center.
The main findings were as follows: 1) late recurrence ≥1 year after ablation was observed in a notable number of patients; 2) in contrast to AP recurring within in the first year after ablation, all patients with late recurrence had a left-sided AP; and 3) with respect to the combined endpoint (ablation failure or recurrence), the anticipated long-term success after the initial ablation procedure may be lower than previously reported (7,8).
As previously reported (5), the majority of AP relapses were observed within the first year post-ablation with nearly one-half of all recurrences occurring within the first month. Those AP were supposedly not completely ablated but AP conduction was most probably temporarily interrupted by edema and tissue swelling after RF application. Upon recovery of AP conduction, both antegrade and/or retrograde conduction might be possible. One may speculate that there are other variables such as neurohumoral and endocrine factors influencing both antegrade and retrograde AP conduction that are still not completely understood. As neurohumoral and endocrine activation varies with age and developmental status in pediatric patients, those factors may have an effect on the occurrence of AVRT and the recognition of AP recurrence.
Antegrade AP conduction has been described to be highly variable in up to 12% of the patients (10,11). Recurrence of AP conduction may not have been detected during the first routine-follow-up visits accordingly.
One remarkable finding of our analysis is the number of patients with recurrence of AP conduction ≥1 year post-ablation (i.e., late recurrence). As most previous studies reported a median follow-up of 12 to 17 months (5,7,8), long-term efficacy after AP ablation may have been systematically overestimated.
Reasons for late recurrence of AP after ablation are not completely understood but may at least in part be identical with those for early recurrence (i.e., lack of complete AP interruption). It is, however, unclear why recurrence of AP conduction becomes manifest so late in some patients. Findings may in part be explained by intermittent AP conduction. In case of exclusively retrograde conducting AP (3 of 6 subjects with late AP recurrence), however, variable occurrence of SVT may be the underlying reason. If symptoms of SVT are not reported properly by young patients and do not prompt the families to see their pediatric cardiologist before the scheduled follow-up visit, late recurrence may systemically be overestimated. Our observation that late recurrence of AP was seen only in left-sided AP is surprising. This may reflect some intrinsic difference in the anatomy of these AP compared with right-sided AP or a procedural factor, such as catheter restriction through the transseptal sheath, that promoted incomplete ablation of these AP. Higher variability of antegrade conduction in left-sided AP may have contributed to this finding. This assumption is supported by 2 recent reports on higher, yet not statistically significant, proportion in left-sided AP with intermittent pre-excitation pattern (10,11). Varying retrograde conduction may have also contributed.
Though we found a lower long-term-success rate with respect to the combined endpoint than was reported before (7,8), these results may represent only an upper limit of “true” long-term ablation success. The fate of concealed AP with retrograde conduction remains unclear if patients do not become symptomatic with repeat AVRT. To verify the results of catheter ablation, repeat invasive EP study would be necessary in all patients.
Although late arrhythmias after catheter ablation of AP have been described (12), it is of note that we did not record any late complications such as secondary arrhythmias including late AV block during long-term follow-up. At the present time, it seems very unlikely that myocardial RF lesions form a substrate for secondary arrhythmias. As data are limited, life-long fate of RF lesions in pediatric patients is still obscure.
This study is limited by its retrospective single-center design and the limited number of patients enrolled. The recognition of AP recurrence was assessed on the basis of clinical presentation of SVT and/or the finding of pre-excitation on ECG. Therefore, AP conduction could systemically be underestimated in individuals with exclusively retrograde AP conduction and a low or no arrhythmia burden. The fidelity of clinical history to rule out this possibility is not known. As timing of AP recurrence was assessed retrospectively by onset of palpitations or first documentation of SVT or pre-excitation, it is possible that timing of true recurrence (i.e., recurrence of AP conduction) was earlier than assessed by definition used in our study. Additionally, Holter analysis were not performed systematically in all patients during late follow-up. Therefore, our finding of no secondary arrhythmia is limited to clinical history and standard ECG traces.
Early recurrence of SVT or pre-excitation occurred in 8% of patients within the first year after RF ablation of pediatric AP. Late recurrences (i.e., >1 year after ablation) were noticed in 2% of the whole study group. With respect to a combined endpoint (primary procedural success/failure and recurrence in patients after successful ablation), a considerable number of patients experienced recurrence of AP conduction or had an unsuccessful primary ablation. Results should be taken into consideration when AP catheter ablation is planned in pediatric patients.
COMPETENCY IN MEDICAL KNOWLEDGE: RF ablation of AP is effective and safe in children. Long-term efficacy (i.e., successful ablation and freedom from recurrence) after the initial procedure is achieved in about 80% of subjects.
TRANSLATIONAL OUTLOOK: As late recurrence of AP conduction was observed, factors contributing to late recurrence have to be identified in order to increase long-term efficacy of RF catheter ablation. Additionally, clinical follow-up beyond 1 year after the initial ablation procedure might be reasonable.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- atrioventricular pathway
- atrioventricular re-entrant tachycardia
- congenital heart defects
- interquartile range
- supraventricular tachycardia
- Received December 29, 2017.
- Revision received February 12, 2018.
- Accepted February 22, 2018.
- 2018 American College of Cardiology Foundation
- Philip Saul J.,
- Kanter R.J.,
- Abrams D.,
- et al.
- Kugler J.D.,
- Danford D.A.,
- Houston K.,
- Felix G.,
- Pediatric EP Society, Radiofrequency Catheter Ablation Registry
- Ceresnak S.R.,
- Dubin A.M.,
- Kim J.J.,
- et al.
- Kiger M.E.,
- McCanta A.C.,
- Tong S.,
- Schaffer M.,
- Runciman M.,
- Collins K.K.
- Mah D.Y.,
- Sherwin E.D.,
- Alexander M.E.,
- et al.