Author + information
- Received August 16, 2017
- Revision received October 3, 2017
- Accepted October 12, 2017
- Published online April 16, 2018.
- Susan P. Etheridge, MDa,∗ (, )
- Carolina A. Escudero, MDb,
- Andrew D. Blaufox, MDc,
- Ian H. Law, MDd,
- Brynn E. Dechert-Crooks, RN, MSNe,
- Elizabeth A. Stephenson, MDf,
- Anne M. Dubin, MDg,
- Scott R. Ceresnak, MDg,
- Kara S. Motonaga, MDg,
- Jonathan R. Skinner, MBChB, MDh,
- Luciana D. Marcondes, MDh,
- James C. Perry, MDi,
- Kathryn K. Collins, MDj,
- Stephen P. Seslar, MDk,
- Michel Cabrera, MDl,
- Orhan Uzun, MDm,
- Bryan C. Cannon, MDn,
- Peter F. Aziz, MDo,
- Peter Kubuš, MDp,
- Ronn E. Tanel, MDq,
- Santiago O. Valdes, MDr,
- Sara Sami, MDr,
- Naomi J. Kertesz, MDs,
- Jennifer Maldonado, MBA, CCRPd,
- Christopher Erickson, MDt,
- Jeremy P. Moore, MDu,
- Hiroko Asakai, MDf,
- LuAnn Mill, RN, BSNt,
- Mark Abcede, MBA, CCRPi,
- Zebulon Z. Spector, MDk,
- Shaji Menon, MDa,
- Mark Shwayder, MDa,
- David J. Bradley, MDe,
- Mitchell I. Cohen, MDv and
- Shubhayan Sanatani, MDw
- aDivision of Cardiology, Department of Pediatrics, Primary Children’s Hospital, University of Utah, Salt Lake City, Utah
- bDivision of Cardiology, Department of Pediatrics, Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada
- cDivision of Pediatric Cardiology, Department of Pediatrics, Cohen Children’s Medical Center of New York, Hofstra-Northwell School of Medicine, New Hyde Park, New York
- dDepartment of Pediatrics, Division of Cardiology, Stead Family Children’s Hospital, University of Iowa, Iowa City, Iowa
- eDivision of Cardiology, Department of Pediatrics, University of Michigan Children’s Hospital, University of Michigan, Ann Arbor, Michigan
- fLabatt Family Heart Centre, Hospital for Sick Children, Toronto, Ontario, Canada
- gDivision of Pediatric Cardiology, Department of Pediatrics, Lucile Packard Children’s Hospital, Stanford University, Palo Alto, California
- hGreenlane Paediatric and Congenital Cardiac Service, Starship Children’s Hospital, University of Auckland, Auckland, New Zealand
- iCardiology Division, Department of Pediatrics, Rady Children’s Hospital, University of California San Diego, San Diego, California
- jDivision of Cardiology, Children’s Hospital Colorado, University of Colorado, Aurora, Colorado
- kDivision of Pediatric Cardiology, Department of Pediatrics, Seattle Children’s Hospital, Seattle, Washington
- lCardiocentro Pediatrico William Soler, Havana, Cuba
- mDepartment of Paediatric Cardiology, University Hospital of Wales, Cardiff, Wales, United Kingdom
- nDepartment of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota
- oDivision of Pediatric Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio
- pChildren's Heart Centre, Charles University and Motol University Hospital, Prague, Czech Republic
- qDepartment of Pediatrics, Benioff Children’s Hospital, University of California San Francisco, San Francisco, California
- rDivision of Pediatric Cardiology, Texas Children’s Hospital, Baylor College of Medicine, Houston Texas
- sNationwide Children’s Hospital, Columbus, Ohio
- tDivision of Pediatric Cardiology in the Department of Pediatrics, Children’s Hospital and Medical Center, Omaha, Nebraska
- uDepartment of Pediatrics, Division of Pediatric Cardiology, UCLA Health System, University of California Los Angeles, Los Angeles, California
- vPhoenix Children’s Hospital, University of Arizona College of Medicine, Phoenix, Arizona
- wDivision of Cardiology, Department of Pediatrics, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
- ↵∗Address for correspondence:
Dr. Susan P. Etheridge, University of Utah and Primary Children’s Hospital, Pediatrics, 81 North Mario Capecchi Drive, Salt Lake City, Utah 84113.
Objectives This study sought to characterize risk in children with Wolff-Parkinson-White (WPW) syndrome by comparing those who had experienced a life-threatening event (LTE) with a control population.
Background Children with WPW syndrome are at risk of sudden death.
Methods This retrospective multicenter pediatric study identified 912 subjects ≤21 years of age with WPW syndrome, using electrophysiology (EPS) studies. Case subjects had a history of LTE: sudden death, aborted sudden death, or atrial fibrillation (shortest pre-excited RR interval in atrial fibrillation [SPERRI] of ≤250 ms or with hemodynamic compromise); whereas subjects did not. We compared clinical and EPS data between cases and subjects.
Results Case subjects (n = 96) were older and less likely than subjects (n = 816) to have symptoms or documented tachycardia. Mean age at LTE was 14.1 ± 3.9 years of age. The LTE was the sentinel symptom in 65%, consisting of rapidly conducted pre-excited atrial fibrillation (49%), aborted sudden death (45%), and sudden death (6%). Three risk components were considered at EPS: SPERRI, accessory pathway effective refractory period (APERP), and shortest paced cycle length with pre-excitation during atrial pacing (SPPCL), and all were shorter in cases than in control subjects. In multivariate analysis, risk factors for LTE included male sex, Ebstein malformation, rapid anterograde conduction (APERP, SPERRI, or SPPCL ≤250 ms), multiple pathways, and inducible atrial fibrillation. Of case subjects, 60 of 86 (69%) had ≥2 EPS risk stratification components performed; 22 of 60 (37%) did not have EPS-determined high-risk characteristics, and 15 of 60 (25%) had neither concerning pathway characteristics nor inducible atrioventricular reciprocating tachycardia.
Conclusions Young patients may experience LTE from WPW syndrome without prior symptoms or markers of high-risk on EPS.
Sudden death in Wolff-Parkinson-White (WPW) syndrome is a rare but potentially preventable problem affecting young, otherwise healthy people. Sudden death is usually a consequence of atrial fibrillation with rapid conduction over an accessory pathway resulting in ventricular fibrillation. Because WPW patients develop atrial fibrillation more frequently than the general population, an important question is whether there is a risk of ventricular fibrillation should atrial fibrillation occur. Assessing accessory pathway conduction properties by using electrophysiology study (EPS) is advocated as a preventive strategy against sudden death, as noninvasive risk stratification tools are imperfect (1–4). Inducible atrioventricular re-entrant tachycardia (AVRT) or EPS data suggesting a pathway capable of rapid anterograde conduction are identified as predictors of malignant arrhythmia (5–8). Because catheter ablation can cure WPW syndrome and eliminate risk (9), the small long-term risk of a life-threatening event (LTE) must be balanced with the immediate albeit low risk of an ablation.
The low event rate of WPW syndrome, reduced further by catheter ablation, makes risk assessment a challenge. Data investigating possible risk factors for LTE in children with WPW syndrome, however, remain critical. In this study, we compared children with WPW syndrome who had experienced an LTE with a control population (WPW syndrome without LTE) to identify characteristics associated with sudden death risk.
This multicenter, international, retrospective case-control study involved 22 centers from 6 countries (United States, Canada, New Zealand, Cuba, Czech Republic, and Wales [United Kingdom]) solicited through the Pediatric and Congenital Electrophysiology Society (PACES). Data collected encompassed the era of catheter ablation in children, from January 1990 through June 2016. All centers obtained local investigational review board approval, and institutional databases were searched to identify children with WPW syndrome. De-identified data were managed using Research Electronic Data Capture (REDCap), hosted at the University of Utah. REDCap is a secure, Web-based application designed to support data capture for research (10). All data were reviewed by the data coordinating center and statistician for appropriateness for inclusion.
Case subjects were children with WPW syndrome who had experienced an LTE at ≤21 years of age. An LTE was defined as sudden death, aborted sudden death, or a clinical episode of pre-excited atrial fibrillation with the shortest pre-excited RR interval (SPERRI) in atrial fibrillation of ≤250 ms, regardless of symptoms or documented pre-excited atrial fibrillation associated with hemodynamic compromise, syncope, or seizure, regardless of the SPERRI. Subjects who experienced pre-excited atrial fibrillation without associated hemodynamic compromise, syncope, or seizure and a SPERRI >250 ms were excluded. Cases of sudden death were included if a pre-mortem electrocardiogram (ECG) and/or EPS proving WPW syndrome was available.
Control subjects were ≤21 years of age with WPW syndrome who had not experienced an LTE or clinical pre-excited atrial fibrillation and had undergone an EPS. For each case subject, 4 age-matched subjects (±24 months of age at EPS or LTE if no EPS was performed) and 4 non–age-matched subjects were selected by each center. Two sets of subjects were selected to potentially mitigate and investigate influences of age and size on ablation outcomes and risk. Matched subjects were selected from the same institution when possible or from other participating centers. Except for analyses involving age, subjects were evaluated as a single control group. Congenital heart disease (CHD) was noted, but cases and subjects were not matched for this variable.
Demographic data included age at presentation, EPS information, and last follow-up examination. Symptoms, documented supraventricular tachycardia (SVT), and hemodynamically significant CHD were noted. Hemodynamically insignificant ventricular and atrial septal defects, ductus arteriosus, mitral valve prolapse, isolated left superior vena cava, and bicuspid aortic valve without stenosis or insufficiency were not considered significant CHD. Details of the LTE were collected, including activity at the time (rest, active but noncompetitive, competitive activity, as determined by the contributing center), type of event (pre-excited atrial fibrillation, aborted sudden death or ventricular fibrillation, or sudden death), and outcome (death, full or near full recovery, or recovery with a neurological deficit). All cases were reviewed by the coordinating center.
By design, an EPS was performed in all subjects. If case subjects had >1 EPS performed, the earliest study with risk stratification data was included for analysis. EPS data collected included determination of conduction properties, location of pathway(s), and induction of tachycardia including orthodromic reciprocating tachycardia (ORT), antidromic reciprocating tachycardia (ART), atrioventricular node reentrant tachycardia, atrial flutter, or atrial fibrillation. We considered risk stratification as performing at least one of the following studies: accessory pathway effective refractory period (APERP), shortest paced cycle length with pre-excitation during atrial pacing (SPPCL) or SPERRI. If the atrial effective refractory period (AERP) was reached before APERP, the AERP was used in place of APERP. An APERP, SPPCL, or SPERRI value of ≤250 ms was considered high-risk. The use of anesthesia was noted. Data for isoproterenol were reported when available. Ablation success and complications were reported.
Frequency tables were generated for all categorical variables SPSS version 20.0 (IBM Corp., Armonk, New York), with chi-square or Fisher exact analyses used to detect differences between case and control subjects. Mean ± SD were reported for continuous variables. Univariate analysis of variance (ANOVA) was used to compare means for continuous variables between cases and subjects. Binomial logistic regression analyses were used to predict risk of LTE (i.e., cases vs. subjects) based on sex and at least one of following variables: APERP, SPERRI, or SPPCL ≤250 ms; presence of Ebstein malformation; inducible atrial fibrillation at EPS; or the presence of >1 accessory pathway. The EPS-derived data were combined for logistic regression analysis because too few subjects had all 3 measurements determined. EPS data for univariate and multivariate analyses were obtained in the baseline state. Receiver-operating characteristic (ROC) curves were constructed to determine the sensitivity and specificity of different cutoff values of APERP, SPERRI, and SPPCL. For some analyses of tachycardia induction, ORT and ART were combined and designated AVRT. Significance was set at a p value of ≤0.05.
Demographic data, entire cohort
A total of 108 cases and 864 subjects were initially entered into the database, but 12 cases were excluded for not meeting LTE criteria. Thus, a total of 912 subjects (96 cases and 816 subjects) were analyzed (the 48 subjects age-matched to excluded subjects were omitted, but the non–age-matched subjects were retained). The 2 control groups did not differ except in age and were combined into a single group for all analyses except for age. Demographic and clinical data are summarized in Table 1. Case subjects were more likely to be male and were older at presentation than non–age-matched subjects. Case subjects were less likely to have experienced symptoms before the LTE than subjects and were more likely to have CHD. The most common lesion was Ebstein malformation (n = 15), more prevalent in case subjects (5.2% vs. 1.2%, respectively; p = 0.004). At last follow-up examination, there were 9 deaths, all in case subjects.
Clinical data, case subjects
Table 2 outlines the characteristics of case subjects and LTE details. Mean age at LTE was 14.1 ± 3.9 years of age with 3 subjects <5 years of age (Table 3). The LTE occurred most often at rest or with noncompetitive activity and was equally likely to be rapidly conducted pre-excited atrial fibrillation and aborted sudden death. There were 6 subjects (6%) who presented with sudden death who had a pre-mortem ECG and/or EPS demonstrate WPW syndrome, and post-mortem evaluation did not reveal an identifiable alternative cause of death. Three case subjects experienced 2 LTEs, and 1 had stable pre-excited atrial fibrillation before experiencing an LTE. Among case subjects, age <12 years (n = 16) was associated with aborted sudden death as the LTE (88% vs 36%,; p <0.0005) and age ≥12 years (n = 80) was associated with pre-excited atrial fibrillation as the LTE (56% vs 13%; p = 0.002).
Clinical SPERRI was reported in 46 cases with pre-excited atrial fibrillation as their LTE (1 was classified as aborted sudden death due to degeneration to ventricular fibrillation). The mean SPERRI was 202 ± 33 ms (range 150 to 320 ms). Two case subjects had pre-excited atrial fibrillation and an unknown SPERRI, 1 with recurrent seizures requiring intubation and a second subject with poor perfusion and hypotension. An additional case subject had syncope while running and a clinical SPERRI upon presentation of 320 ms.
Sudden death or aborted sudden death was the presenting symptom in 31 case subjects, and pre-excited atrial fibrillation was the presenting symptom in 31 subjects. There were 38 (40%) of case subjects who had not complained of previous symptoms before the LTE. There were 56 case subjects (58%) who were not known to have WPW syndrome before the LTE. Of these, 32 (33%) were symptom free. The remaining 24 reported prior symptoms including documented SVT (n = 1), palpitations alone (n = 11), palpitations and syncope (n = 5), palpitations and near syncope (n = 4), and syncope alone (n = 3).
Full or near full recovery was likely in case subjects after LTE. Five subjects recovered with a neurological deficit; of these, 1 subject had acute kidney failure, and 1 had right leg compartment syndrome after extracorporeal membrane oxygenation support. The LTE was sudden death in 6 cases. Three additional cases were removed from life support due to devastating neurological injury. One death occurred in a child who became a heart transplant donor, and WPW syndrome was diagnosed in the recipient subsequent to transplantation.
Electrophysiology study data, entire cohort
Table 4 outlines EPS data and ablation outcomes. EPS data were available in all subjects and 91% of cases. EPS data were not available in 8 case subjects, 7 of whom died without a previous EPS, and an infant who had yet to undergo EPS (Table 3). In 4 case subjects, EPS data were from a procedure performed before LTE. One case subject had EPS performed at a nonparticipating institution, and data were not available. One case subject was lost to follow-up after an acutely successful ablation. He presented in ventricular fibrillation with unsuccessful resuscitation. He had mild Ebstein malformation with trivial tricuspid regurgitation; autopsy findings were otherwise unremarkable. In the remaining 83 case subjects, EPS data were from a procedure after the LTE, including EPS and ablation data from a procedure performed in a recipient of a heart transplanted from a donor with WPW syndrome.
Table 4 outlines tachycardias induced. Case subjects were less likely to have ORT but more likely to have ART, atrial flutter, and atrial fibrillation.
Accessory pathway anterograde functional properties
Risk stratification, defined as the determination of accessory pathway anterograde functional property (APERP, SPERRI, or SPPCL) during EPS, was undertaken in 89% of case and 94% of control subjects. There were 60 of 87 case subjects (69%) who underwent an EPS with ≥2 accessory pathway functional properties determined. Case subjects had significantly shorter APERP, SPERRI, and SPPCL values and were more likely to have multiple accessory pathways (Table 4, Figure 1). Case subjects were more likely to have at least 1 functional property considered high-risk. There were values for EPS-derived SPERRI reported in 39 (45%) of case subjects (mean 247 ± 61 ms). However, in 14 of 39 (36%), the SPERRI was >250 ms. In 13 of these subjects, the procedure was performed using general anesthesia; in 1 subject, conscious sedation was used. This is not different from the group where the SPERRI was ≤250 ms, 18 had general anesthesia and 7 had conscious sedation (p = 0.20). Among 60 case subjects who had risk stratification that included ≥2 accessory pathway characteristics, 22 of 60 (37%) did not have concerning pathway characteristics, and 15 of 60 (25%) had neither concerning pathway characteristics nor inducible AVRT. Figure 1 shows the proportion with pathway functional characteristics considered high-risk (APERP, SPERRI, or SPPCL of ≤250 ms) and with multiple accessory pathways. Figure 2 shows the distribution of EPS data in cases and subjects, and although there is overlap between case and subjects, a low-risk cutoff can be noted. No case subject had a SPERRI >370 ms or an APERP >400 ms. One case subject had a SPPCL >440 ms. Figure 3 demonstrates ROC curves for the risk stratification maneuvers and demonstrates no significant differences between the areas under the curve for each risk stratification maneuver.
When EPS data from case subjects with pre-excited atrial fibrillation were compared to those of subjects with aborted sudden death, there were no significant differences in mean APERP, SPERRI, or SPPCL values and no differences in the proportion with any of these values ≤250 ms or the presence of multiple accessory pathways.
EPS data during isoproterenol infusion were not available for the entire cohort (Table 5). Isoproterenol therapy resulted in a shortening of pathway functional properties in both groups, although case subjects continued to have significantly shorter SPERRI and SPPCL. Only 3 case subjects had all 3 functional characteristic studies performed while they were receiving isoproterenol therapy, too few to make meaningful conclusions.
Predictors of life-threatening events
Factors associated with LTE were identified by univariate analysis (Table 6), including APERP, SPERRI, and SPPCL ≤250 ms; presence of Ebstein malformation; inducible atrial fibrillation at EPS; and presence of multiple pathways. Logistic regression was statistically significant (chi-square: 5 = 82.94; df = 5; p < 0.0005). Table 7 outlines the features that were independently associated with increased odds of having an LTE.
Of those who underwent EPS, ablation was attempted in 98% of cases and 97% of subjects. Success was lower in case subjects (82% vs. 93%, respectively; p = 0.001). Table 8 outlines the pathway locations. More complications were noted in case subjects (Table 4), including atrioventricular block (2.3% vs. 0.2%, respectively; p = 0.048). There were no deaths resulting from EPS or ablation.
This multicenter, international study is the largest to have addressed pediatric WPW syndrome and has increased our understanding of risk. Although the children were treated in the contemporary era of catheter ablation, sudden death still occurred. An LTE was the sentinel event in 65%, with sudden death or aborted sudden death sentinel in nearly 1 of 3 subjects. Importantly, case subjects were less likely than subjects to have experienced previous symptoms.
In this study, we sought to better characterize LTEs in children. Events occurred most often in adolescent males who were not engaged in competition. Although competitive athletics are considered to increase risk (11–14), sports restriction would not have prevented LTEs in the 73% of our case subjects whose events did not occur with competition. Our data are consistent with previous series exploring sudden death in the young, where most events occurred during rest or sleep (15–17). The 10% of events occurring with sports, however, remains disproportionately high when one considers the percentage of time engaged in sports compared with time spent at rest and in noncompetitive activities. Thus, our data do not support unrestricted sports participation in patients with WPW syndrome but demonstrate that sports restriction does not keep children safe.
Many studies have assessed pacing maneuvers for risk stratification. A prospective study found shorter APERP and degeneration into atrial fibrillation after AVRT were associated with development of malignant arrhythmias (9). Other studies have proposed that SPERRI best predicts risk, as patients with ventricular fibrillation had a SPERRI ≤250 ms (7). Our data suggest that substantial risk is present even without evidence of rapid anterograde pathway conduction at EPS, as commonly defined. Instead, the cutoff value at EPS identified in this cohort was higher: no case subject had an APERP >400 ms or a SPERRI >370 ms.
Assessing each EPS-determined risk factor is not always possible. If AERP is reached before APERP, the true APERP cannot be determined. Assessment of SPERRI requires induction of atrial fibrillation, which is not always possible, although SPCCL may be used as a surrogate. Atrial fibrillation was induced, and a SPERRI of >250 ms was reported in 36% of case subjects and in 82% of subjects. This is in contrast to a study where symptomatic children with WPW syndrome, syncope and atrial fibrillation had a SPERRI <220 ms (18). Although an EPS that included all 3 functional characteristics was not always performed, 60 case subjects had at least 2 characteristics measured. Of these, 37% would have been classified as low-risk if functional characteristics alone were used. SVT induction at EPS is also associated with increased risk (19,20). In 25% of case subjects who had a more complete EPS performed, there were neither concerning pathway characteristics nor inducible AVRT. Thus, had EPS been undertaken solely for risk stratification, these children would not have had a conventional indication for ablation. These data suggest that EPS-derived risk factors developed in adult patients may not be applicable to children.
Historically, decisions about patient management were based on the distinction between asymptomatic and symptomatic patients. This approach has been called into question. In >2,000 patients with WPW syndrome, symptomatic patients were more likely to have had an ablation than asymptomatic patients (9). However, except for symptoms, there were no differences in clinical or EPS characteristics. Present data confirm the fact that asymptomatic WPW syndrome is not without risk, and although malignant arrhythmias correlate better with EPS-derived risk stratification data than with symptoms, EPS is an imperfect predictor, and a low threshold for ablation should be considered.
In the seminal 1979 series (7), the only asymptomatic WPW patients who presented with ventricular fibrillation were children. The lack of symptoms in children may be a lack of recognition of symptoms, failure to report them, or an insufficient period over which to develop them; an asymptomatic child may be a pre-symptomatic child. We often strive to treat children in the pre-symptomatic phase of a disease, most crucially when the first symptom may be sudden death.
Serious complications from catheter ablation are rare but are not uniform across childhood (21–23). Ablation success rates in very young children may be similar to those in older, larger patients, but rates of adverse events may be higher, and ablation should not be the routine approach to the smallest patients (24). In addition to procedural complications, there may be potential for lesions that are larger than intended or lesion growth over time in these patients (23–25). The small but potentially life-long risk in WPW syndrome must be balanced with the slight but immediate risk of ablation.
In the present report, most EPS were performed with subjects under general anesthesia, common in pediatric EPS (26). Initial high-risk criteria were derived from procedures without general anesthesia, which is known to affect pathway conduction and decrease SVT induction (7,14,27). General anesthesia may limit comparison with historical data and limit optimal EPS risk stratification. The role of isoproterenol therapy during risk stratification is not clearly defined. Isoproterenol has been shown to increase the number of subjects meeting risk criteria for ablation (28) and may decrease the specificity of the EPS (29). Data for isoproterenol therapy were available in a small proportion of our subjects. Similar to previous reports (30), pathway functional properties shortened in case and control groups, increasing the number with pathway characteristics suggesting high-risk. In order to prevent LTE, we may need to consider using isoproterenol and/or performing studies without general anesthesia to improve risk assessment, even at the risk of decreasing specificity.
When case and control patients were compared using multivariate analysis, Ebstein malformation was independently associated with risk. Many patients with Ebstein malformation have WPW syndrome and, not uncommonly, multiple pathways (31). The annual hazard rate for death, highest in the first year of life, persists throughout life with continuing attrition in part due to sudden death (32). Although procedures may be difficult, patients with Ebstein malformation improve after ablation (33,34).
Ablation was undertaken in 96% of subjects and was less successful in case subjects who also experienced increased complications. Multiple pathways and a higher proportion with Ebstein malformation may have contributed to this lower success. The increased complications may be related to more aggressive ablation attempts in this high-risk population, coupled with a possible selection bias in the control group. This study provides data for procedural success and risk in the control population. Comparable to previous pediatric ablation data, success rates were high, complications rare, and there were no deaths (35,36).
This is a retrospective study with inherent limitations. There was no uniform clinical or EPS evaluation, and very few subjects had an EPS that included all 3 functional characteristics. There are limited data for noninvasive testing, and this study is not powered to outline a noninvasive strategy for risk stratification. There are strategies using pharmacologic testing for risk stratification (37–39), that were not evaluated here. For control subjects, we used children with available EPS data. One cannot conclude that this population is necessarily low risk but is only representative of the population who undergo an EPS, and we cannot know if these children would have gone on to experience an LTE without ablation. We cannot be certain that the 2 infants presenting with aborted sudden death experienced ventricular fibrillation versus a prolonged episode of unrecognized SVT. Operator variability in arrhythmia induction may have contributed to the lack of SVT induction and SPERRI data. One could speculate that, after an LTE, as an ablation was indicated, and a less rigorous EPS risk assessment was performed. Limited EPS data for isoproterenol therapy allow for only limited conclusions. The significant differences in ablation outcomes and complications between control and case subjects may reflect selection bias, although outcomes are similar to data reported in large pediatric ablation series (23,35,40).
This large contemporary study of children with WPW syndrome identified 96 children with an LTE, many without previous symptoms. Although most would have been identified as high-risk, a third would have been missed. Male sex, Ebstein malformation, inducible atrial fibrillation, and conventional EPS measurements of risk were independently associated with LTE. Although the lifetime risk of sudden death in WPW syndrome is low, it is “front loaded” in the young (41). Indications to perform a catheter ablation are varied and not entirely based on risk. Occupation choices, insurability, and the psychological impact of having WPW syndrome may influence this decision. Because EPS is an imperfect predictor and the risk of an ablation is low, once an invasive EPS is performed, moving forward to a catheter ablation seems appropriate. We advocate a low threshold for catheter ablation to cure WPW syndrome in children after careful consideration of age and size-based risks.
COMPETENCY IN MEDICAL KNOWLEDGE: In children with WPW syndrome, an LTE can be the first symptom, and risk stratification using clinical and EPS-derived data are imperfect and fail to identify all those at risk.
TRANSLATIONAL OUTLOOK: A prospective study of children with WPW syndrome and the WPW syndrome pattern on ECG is needed to better assess the burden of sudden death and the risk in children with WPW syndrome where a catheter ablation is required.
The authors thank the Fischerkeller Rock-for-the-Heart Foundation for their support and interest in this project and their ongoing support of research in children with WPW syndrome. They also thank the Pediatric and Congenital Electrophysiology Society, without which the research team would not have met, organized, or collaborated.
Dr. Kubuš is supported by the Ministry of Health, Czech Republic (MHCZ-DRO), University Hospital Motol, Prague, Czech Republic 00064203. All other 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
- accessory pathway effective refractory period
- antidromic reciprocating tachycardia
- atrioventricular reciprocating tachycardia
- congenital heart disease
- electrophysiology study
- life-threatening event
- orthodromic reciprocating tachycardia
- shortest pre-excited RR interval in atrial fibrillation
- shortest pre-excited paced cycle length with atrial pacing
- supraventricular tachycardia
- Wolff-Parkinson-White syndrome
- Received August 16, 2017.
- Revision received October 3, 2017.
- Accepted October 12, 2017.
- 2018 American College of Cardiology Foundation
- Kiger M.E.,
- McCanta A.C.,
- Tong S.,
- Schaffer M.,
- Runciman M.,
- Collins K.K.
- Congenital Electrophysiology S,
- Heart Rhythm S,
- et al.
- Sharma A.D.,
- Yee R.,
- Guiraudon G.,
- Klein G.J.
- Dalili M.,
- Vahidshahi K.,
- Aarabi-Moghaddam M.Y.,
- Rao J.Y.,
- Brugada P.
- Bromberg B.I.,
- Lindsay B.D.,
- Cain M.E.,
- Cox J.L.
- Klein G.J.,
- Prystowsky E.N.,
- Yee R.,
- Sharma A.D.,
- Laupacis A.
- Pappone C.,
- Vicedomini G.,
- Manguso F.,
- et al.
- Heidbuchel H.,
- Corrado D.,
- Biffi A.,
- et al.
- Maron B.J.,
- Doerer J.J.,
- Haas T.S.,
- Tierney D.M.,
- Mueller F.O.
- Mellor G.,
- Raju H.,
- de Noronha S.V.,
- et al.
- Finocchiaro G.,
- Papadakis M.,
- Behr E.R.,
- Sharma S.,
- Sheppard M.
- Pappone C.,
- Santinelli V.,
- Rosanio S.,
- et al.
- Wellens H.J.
- Schaeffer B.,
- Hoffmann B.A.,
- Meyer C.,
- et al.
- Blaufox A.D.,
- Felix G.L.,
- Saul J.P.,
- Pediatric Catheter Ablation Registry
- Saul J.P.,
- Hulse J.E.,
- Papagiannis J.,
- Van Praagh R.,
- Walsh E.P.
- Pecht B.,
- Maginot K.R.,
- Boramanand N.K.,
- Perry J.C.
- Moore J.P.,
- Kannankeril P.J.,
- Fish F.A.
- Kubus P.,
- Vit P.,
- Gebauer R.A.,
- Materna O.,
- Janousek J.
- Celermajer D.S.,
- Bull C.,
- Till J.A.,
- et al.
- Pressley J.C.,
- Wharton J.M.,
- Tang A.S.,
- Lowe J.E.,
- Gallagher J.J.,
- Prystowsky E.N.
- Walsh E.P.
- Kugler J.D.,
- Danford D.A.,
- Houston K.A.,
- Felix G.
- Van Hare G.F.,
- Lesh M.D.,
- Stanger P.
- Klein G.J.,
- Gula L.J.,
- Krahn A.D.,
- Skanes A.C.,
- Yee R.