EDITORIAL COMMENT
Asymptomatic Wolff-Parkinson-White Syndrome in ChildrenAn Unnatural History?*
Seshadri Balaji, MBBS, MRCP(UK), PhD, FACC*
Department of Pediatrics (Cardiology), Oregon Health & Science University, Portland, Oregon
* Reprint requests and correspondence: Dr. Seshadri Balaji, 707 SW Gaines Street, Mailcode: CDRC-P, Portland, Oregon 97239 (Email: balajis{at}ohsu.edu).
Key Words: sudden death • WPW syndrome • catheter ablation • syncope
The management of an asymptomatic child incidentally discovered to have Wolff-Parkinson-White (WPW) syndrome on electrocardiogram (ECG) is a controversial issue. One big impediment to settling the controversy is our ignorance about the natural history of asymptomatic WPW syndrome. In this issue of the Journal, Santinelli et al. (1) report the largest cohort (to date) of children with asymptomatic WPW syndrome intensively followed for a period of time. Patients were identified incidentally or through the mass ECG screening program for athletes instituted in Italy since 1982.
All children (age 8 to 12 years) underwent an electrophysiology (EP) study at the start of the prospective protocol. They were followed every 6 months with an ECG and a 24-h Holter monitor. The primary end point was the first arrhythmic event. Over a median follow-up of 57 months, 51 of 133 children became symptomatic. Of these, 19 had potentially life-threatening arrhythmias. Interestingly, some children with potentially life-threatening arrhythmias had minimal (n = 5) or atypical symptoms (n = 8) such as nausea, sudden tiredness with anxiety, abdominal pain and swelling, and inability to concentrate while playing. Factors associated with increased risk were the presence of multiple accessory pathways and an accessory pathway effective refractory period (APERP) <240 ms. Atrioventricular re-entry tachycardia (AVRT) inducibility did not prove significant on multivariate analysis. What are the lessons of this study and how do we incorporate its findings into clinical practice? Some background first ...
While it commonly presents with paroxysmal AVRT, WPW syndrome may rarely cause sudden death (SD) due to atrial fibrillation (AF) being rapidly conducted to the ventricle over the accessory pathway resulting in ventricular fibrillation (2,3). In some patients, SD may be the presenting symptom. Deal et al. (4) reported 42 SDs in children with WPW syndrome. Of these, in 20, SD was the presenting symptom.
The approach to the asymptomatic patient is now significantly impacted by the availability of EP and catheter ablation (CA). However, EP and CA are invasive procedures with a potential for complications that could be unacceptable for the asymptomatic patient; hence, the need for careful and objective risk-benefit analysis.
EP can help identify patients at risk for developing symptoms and SD due to WPW syndrome. Inducibility of AVRT, a shorter APERP (<240 ms), a shorter pre-excited RR interval during induced AF (<240 ms), the presence of multiple pathways, and septal and right-sided pathway locations appear to identify a higher-risk group (3,5–7).
Some authorities have suggested that noninvasive risk stratification with Holter monitoring, exercise stress testing, and pharmacologic testing should be performed before invasive studies are considered (8). However, the sensitivity and specificity of noninvasive testing has been shown to be poor (9,10).
Transesophageal EP may be a semi-invasive technique to avoid the potential vascular complications of intracardiac EP (11). However, transesophageal EP is not entirely risk free. High output pacing may be required to activate the atrium from the esophagus, which can be painful and requires the use of heavy sedation (12).
The group from Milan has recently made major contributions to our understanding of the asymptomatic patient with WPW syndrome. They reported the ability of EP testing to risk stratify asymptomatic patients (13). Of the 162 patients (adults and children) studied, only 4 of the 115 patients noninducible for supraventricular tachycardia (SVT) went on to develop clinical SVT during a mean follow-up of 37.7 months. Of the 47 inducible patients, 21 developed SVT and 8 AF. And, of these 8 with AF, 2 had near-miss SD, and 1 died suddenly.
The same group also showed that prophylactic CA in asymptomatic WPW syndrome patients (children and adults) reduces the likelihood of arrhythmia (14). Of 37 patients with inducible SVT (at EP study) who underwent ablation, only 2 had SVT at follow-up (both had AV nodal re-entry tachycardia) while of 35 with inducible SVT randomized to no treatment, 21 had SVT at follow-up.
Their previous study in children between 5 and 12 years of age also suggested that prophylactic CA significantly reduces symptoms (15). Of those with inducible SVT, only 1 of the 27 randomized to ablation developed SVT whereas 7 of 20 randomized to no treatment did, and 1 from the latter group died suddenly.
The major message of the studies from Milan would be that the natural history of asymptomatic WPW syndrome in children is not benign and that EP study provides excellent risk stratification. Patients who are noninducible with a long APERP may be followed without treatment, but those who are inducible or have a short APERP should be considered for ablation. This take-home message is at variance with previous studies and with current guidelines from major cardiology organizations.
Prior studies suggest that SD is rare in an asymptomatic patient with WPW syndrome. Leitch et al. (16) showed no SDs in 75 initially asymptomatic patients followed for a median of 4.3 years. The population-based study of the natural history of WPW syndrome by Munger et al. (17) had 113 WPW patients of whom 53 were asymptomatic at detection. While there were 2 SDs in the symptomatic group, there were none in the asymptomatic patients. Goudevenos et al. (18) followed 157 patients with incidentally discovered WPW syndrome for an average of 55 months with no SDs in their cohort. Inoue et al. (19) followed 57 children detected to have WPW syndrome during screening ECGs for almost 8 years on average, again with no SDs.
Current guidelines from the American Heart Association, American College of Cardiology, and the European Society of Cardiology restrict ablation for asymptomatic WPW syndrome to those in high-risk occupations and professional athletes (20). The Heart Rhythm Society expert consensus is that ablation for asymptomatic WPW syndrome in children age >5 years is a class IIB indication and that in those age <5 years it is a class III indication (21).
The main difference between prior studies and the study of Santinelli et al. (1) is the intensity of monitoring and the credence given to atypical symptoms, which are often dismissed as being noncardiac, in the current study. This study, therefore, alerts us to the importance of these atypical symptoms in WPW patients.
Interestingly, current practice by pediatric electrophysiologists may be more in line with the Milan group recommendations. Campbell et al. (22) surveyed the members of the PACES (Pediatric and Congenital Electrophysiology Society) study group. Of 43 respondents (of whom 37 had been performing ablation for >5 years), 36 used EP study to risk-stratify children with asymptomatic WPW syndrome. Most (33 of 43, 77%) would also perform ablation on children with a shortest pre-excited RR during AF of <240 mm, and 19 of 43 (44%) would have ablated those with APERP <240 ms. Only 11 of 43 (26%) would ablate those with inducible SVT alone. Special consideration of ablation was given by these physicians to patients considering high-risk careers; competitive athletes; and those with coexisting congenital heart disease, asthma, and attention deficit disorder likely to require medical management with drugs.
There are some caveats to the natural history study by Santinelli et al. (1). First, children <5 years old were excluded by design, and all children were >8 years old. Second, there was a high proportion of competitive athletes picked up during the Italian countrywide ECG screening program for competitive athletes.
In summary, this report by Santinelli et al. (1) further reinforces the notion that children with asymptomatic WPW syndrome should undergo an EP study. However, prudence dictates that noninvasive testing with Holter and exercise test (if the Holter does not show intermittent pre-excitation) should be considered before the EP study. It may also be wise to consider transesophageal EP rather than proceeding directly to intracardiac testing. The exact age at which the EP study should be done is unclear, but >8 years seems a reasonable age cutoff. Those who have a potentially dangerous pathway (as defined by the presence of multiple pathways or a short APERP) should probably undergo ablation as long as it is felt to be reasonably safe. The physician involved needs to use special care and discretion in making this decision and must especially consider the success rate and complication rate in his/her hands. While success rates for CA have been improving, serious complications still occur in a small minority of patients (23,24).
Lastly, the findings of the Milan group suggest a more malignant natural history in their cohort than previous reports (16–19). It is advisable to perform further studies in other ethnic/geographic populations before these findings can be accepted in all countries. Despite these caveats, the findings in this study should prompt a reconsideration of current guidelines by professional organizations in the area of pediatric arrhythmia.
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Footnotes
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* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
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References
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1. Santinelli V, Radinovic A, Manguso F, et al. The natural history of asymptomatic ventricular pre-excitation: a long-term prospective follow-up study of 184 asymptomatic children J Am Coll Cardiol 2009;53:275-280.[Abstract/Free Full Text]2. Dreifus LS, Haiat R, Watanabe Y, Arriaga J, Reitman N. Ventricular fibrillation. A possible mechanism of sudden death in patients and Wolff-Parkinson-White syndrome. Circulation 1971;43:520-527.[Abstract/Free Full Text] 3. Klein GJ, Bashore TM, Sellers TD, Pritchett EL, Smith WM, Gallagher JJ. Ventricular fibrillation in the Wolff-Parkinson-White syndrome N Engl J Med 1979;301:1080-1085.[Abstract] 4. Deal BJ, Dick M, Beerman L, et al. Cardiac arrest in young patients with Wolff-Parkinson-White syndrome(abstr) Pacing Clin Electrophysiol 1995;18:815.[CrossRef] 5. Bromberg BI, Lindsay BD, Cain ME, Cox JL. Impact of clinical history and electrophysiologic characterization of accessory pathways on management strategies to reduce sudden death among children with Wolff-Parkinson-White syndrome J Am Coll Cardiol 1996;27:690-695.[Abstract] 6. Timmermans C, Smeets JL, Rodriguez LM, Vrouchos G, van den Dool A, Wellens HJ. Aborted sudden death in the Wolff-Parkinson-White syndrome Am J Cardiol 1995;76:492-494.[CrossRef][Web of Science][Medline] 7. Harahsheh A, Du W, Singh H, Karpawich PP. Risk factors for atrioventricular tachycardia degenerating to atrial flutter/fibrillation in the young with Wolff-Parkinson-White Pacing Clin Electrophysiol 2008;31:1307-1312.[Medline] 8. Wellens HJ. Should catheter ablation be performed in asymptomatic patients with Wolff-Parkinson-White syndrome?. When to perform catheter ablation in asymptomatic patients with a Wolff-Parkinson-White electrocardiogram. Circulation 2005;112:2201-2207discussion 2216.[Free Full Text] 9. Gaita F, Giustetto C, Riccardi R, Mangiardi L, Brusca A. Stress and pharmacologic tests as methods to identify patients with Wolff-Parkinson-White syndrome at risk of sudden death Am J Cardiol 1989;64:487-490.[CrossRef][Web of Science][Medline] 10. Sharma AD, Yee R, Guiraudon G, Klein GJ. Sensitivity and specificity of invasive and noninvasive testing for risk of sudden death in Wolff-Parkinson-White syndrome J Am Coll Cardiol 1987;10:373-381.[Abstract] 11. Brembilla-Perrot B, Chometon F, Groben L, et al. Interest of non-invasive and semi-invasive testings in asymptomatic children with pre-excitation syndrome Europace 2007;9:837-843.[Abstract/Free Full Text] 12. Anier A, Kaik J, Meigas K. A novel method for reducing pain sensation at transesophageal atrial stimulation Conf Proc IEEE Eng Med Biol Soc 2007;2007:923-926.[Medline] 13. Pappone C, Santinelli V, Rosanio S, et al. Usefulness of invasive electrophysiologic testing to stratify the risk of arrhythmic events in asymptomatic patients with Wolff-Parkinson-White pattern: results from a large prospective long-term follow-up study J Am Coll Cardiol 2003;41:239-244.[Abstract/Free Full Text] 14. Pappone C, Santinelli V, Manguso F, et al. A randomized study of prophylactic catheter ablation in asymptomatic patients with the Wolff-Parkinson-White syndrome N Engl J Med 2003;349:1803-1811.[Abstract/Free Full Text] 15. Pappone C, Manguso F, Santinelli R, et al. Radiofrequency ablation in children with asymptomatic Wolff-Parkinson-White syndrome N Engl J Med 2004;351:1197-1205.[Abstract/Free Full Text] 16. Leitch JW, Klein GJ, Yee R, Murdock C. Prognostic value of electrophysiology testing in asymptomatic patients with Wolff-Parkinson-White pattern Circulation 1990;82:1718-1723.[Abstract/Free Full Text] 17. Munger TM, Packer DL, Hammill SC, et al. A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953–1989 Circulation 1993;87:866-873.[Abstract/Free Full Text] 18. Goudevenos JA, Katsouras CS, Graekas G, Argiri O, Giogiakas V, Sideris DA. Ventricular pre-excitation in the general population: a study on the mode of presentation and clinical course Heart 2000;83:29-34.[Abstract/Free Full Text] 19. Inoue K, Igarashi H, Fukushige J, Ohno T, Joh K, Hara T. Long-term prospective study on the natural history of Wolff-Parkinson-White syndrome detected during a heart screening program at school Acta Paediatr 2000;89:542-545.[Medline] 20. Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias) J Am Coll Cardiol 2003;42:1493-1531.[Free Full Text] 21. Friedman RA, Walsh EP, Silka MJ, et al. NASPE Expert Consensus Conference: radiofrequency catheter ablation in children with and without congenital heart disease. Report of the writing committee. North American Society of Pacing and Electrophysiology Pacing Clin Electrophysiol 2002;25:1000-1017.[CrossRef][Medline] 22. Campbell RM, Strieper MJ, Frias PA, Collins KK, Van Hare GF, Dubin AM. Survey of current practice of pediatric electrophysiologists for asymptomatic Wolff-Parkinson-White syndrome Pediatrics 2003;111:e245-e247.[Abstract/Free Full Text] 23. Kugler JD, Danford DA, Houston K, Felix G. Radiofrequency catheter ablation for paroxysmal supraventricular tachycardia in children and adolescents without structural heart disease. Pediatric EP Society, Radiofrequency Catheter Ablation Registry. Am J Cardiol 1997;80:1438-1443.[CrossRef][Web of Science][Medline] 24. Van Hare GF, Javitz H, Carmelli D, et al. Prospective assessment after pediatric cardiac ablation: demographics, medical profiles, and initial outcomes J Cardiovasc Electrophysiol 2004;15:759-770.[CrossRef][Web of Science][Medline]
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