- Email: [email protected]
Lone Atrial Fibrillation in the Young – Perhaps Not So “Lone”?
Lone Atrial Fibrillation in the Young – Perhaps Not So “Lone”? Scott R. Ceresnak, MD1, Leonardo Liberman, MD2, Eric S. Silver, MD2, Steven B. Fishberger, MD3, Gregory J. Gates, PhD4, Lynn Nappo, RN1, Joseph Mahgerefteh, MD1, and Robert H. Pass, MD1 Objective To determine if pediatric patients with a history of lone atrial fibrillation (AF) have other forms of supraventricular tachycardia (SVT) that may potentially trigger AF.
Study design A multicenter review of patients with lone AF who underwent electrophysiology (EP) study from 2006-2011 was performed. Inclusion criteria: age #21 years, normal ventricular function, structurally normal heart, history of AF, and EP study and/or ablation performed. Exclusion criteria: congenital heart disease or cardiomyopathy. Patient demographics, findings at EP study and follow-up data were recorded. Results Eighteen patients met inclusion criteria. The mean age was 17.9 2.2 years, weight was 82 21 kg, body mass index was 27 6, and 15 (83%) were males. Eleven (61%) were overweight or obese. Seven (39%) had inducible SVT during EP study: 5 atrioventricular nodal re-entry tachycardia (71%) and 2 concealed accessory pathways with inducible atrioventricular re-entry tachycardia (29%). All 7 patients with inducible SVT underwent radiofrequency ablation. There were no complications during EP study and/or ablation for all 18 patients. The mean follow-up was 1.7 1.5 years and there were no recurrences in the 7 patients who underwent ablation. There were 2 recurrences of AF in patients with no other form of SVT during EP study. Conclusions Inducible SVT was found in 39% of pediatric patients undergoing EP study for lone AF. EP study should be considered for pediatric patients presenting with lone AF. (J Pediatr 2013;162:827-31).
L
one atrial fibrillation, or atrial fibrillation (AF) in patients with a structurally and functionally normal heart, is a rare dysrhythmia in children and adolescents. Although AF is common in the adult population, in young people it is rare in the absence of significant structural or congenital heart disease.1 Persistent or recurrent AF carries inherent risks and morbidities which include stroke, heart failure, and death.2 There are sporadic reports in the literature on patients who have other forms of supraventricular tachycardia (SVT), such as atrioventricular re-entry tachycardia (AVRT), atrioventricular nodal re-entry tachycardia (AVNRT), and ectopic atrial tachycardia (EAT), that may trigger AF and there are limited reports of ablation for these forms of SVT intended to prevent recurrence of AF.3-8 We sought to determine the frequency of additional forms of SVT in young people who present with lone AF. We hypothesized that young patients with lone AF may have additional forms of SVT (ie, AVRT, AVNRT, and EAT) that may be a trigger for AF. In addition, we theorize that electrophysiology (EP) study and ablation of their additional form of SVT may help prevent further recurrences of AF. Secondary aims of the study were to describe the clinical presentation, management, and patient outcomes of children and adolescents with lone AF.
Methods After approval was obtained by the Institutional Review Board, a multicenter retrospective analysis of patients who underwent EP testing and/or ablation due to a history of lone AF between 2006 and 2011 was performed. The data collected were obtained from three pediatric arrhythmia centers (The Children’s Hospital of Montefiore, The Morgan Stanley Children’s Hospital of New York, and Miami Children’s Hospital). In this investigation, lone AF was defined as a history of AF in the setting of a structurally and functionally normal heart with normal right and left ventricular size and function. The inclusion criteria were patients #21 years of age, with a history of lone AF, who underwent invasive EP testing and/or ablation. Patients with a history of structural or congenital heart disease, a prior history of cardiac surgery, a history of renal or pulmonary disease, or a prior history of EP study and/or ablation due to a known history of SVT or WolffFrom the Pediatric Arrhythmia Service, Division of Parkinson-White syndrome were excluded. Pediatric Cardiology, The Children’s Hospital at 1
AF AVNRT AVRT BMI EAT EP RF SVT
Atrial fibrillation Atrioventricular nodal re-entry tachycardia Atrioventricular re-entry tachycardia Body mass index Ectopic atrial tachycardia Electrophysiology Radiofrequency Supraventricular tachycardia
Montefiore, Albert Einstein College of Medicine, Bronx, NY; 2Division of Pediatric Cardiology, The Morgan Stanley Children’s Hospital, New York, NY; 3Division of Pediatric Cardiology, Department of Pediatrics, Miami Children’s Hospital, Miami, FL; and 4Pediatric Arrhythmia Service, Division of Pediatric Cardiology, Department of Pediatrics, Bronx, NY The authors declare no conflicts of interest. Portions of this study were presented at the Annual Scientific Session of the American College of Cardiology, March 25, 2012, in Chicago, IL. 0022-3476/$ - see front matter. Copyright ª 2013 Mosby Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2012.09.016
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The following data were obtained for each patient: demographic data (age, height, weight, sex), cardiac function and anatomy on echocardiography, urine toxicology screen at presentation, clinical presentation and management of AF, EP study and ablation findings, and follow-up data. Overweight was defined by a body mass index (BMI) of 25-30 and obese by a BMI >30. A clinically indicated EP study was performed on each patient after informed consent was obtained. Anti-arrhythmic medications were stopped at least 5 half-lives prior to the procedure and anti-coagulants were stopped at least 1 week prior. All patients underwent EP study at least 6 weeks after their initial presentation. Patients were given intravenous sedation or general anesthesia at the discretion of the physician performing the procedure. Patients underwent an initially limited EP study with 1 or 2 catheters placed via the right femoral vein with a catheter placed in the coronary sinus and the right ventricular apex or His and right ventricular apex. Standard atrial and ventricular pacing protocols were employed that were similar at each center, with rapid atrial pacing, up to double atrial extrastimulus testing, ventricular overdrive pacing, and single ventricular extrastimulus testing. Testing was repeated routinely with administration of intravenous isoproterenol in an attempt to induce SVT. Adenosine was routinely given during sinus rhythm and with ventricular pacing to help elucidate the presence or absence of an accessory pathway. If SVT was inducible, additional EP diagnostic catheters were then placed and an ablation was attempted. Radiofrequency (RF) energy was used as the first line tool for ablation with cryotherapy reserved for locations near the compact atrioventricular node at the discretion of the operator. Statistical Analyses Statistical analysis was performed using SPSS software (SPSS Inc, Chicago, Illinois). Categorical and dichotomous vari-
Vol. 162, No. 4 ables were expressed as percentages and continuous variables were expressed as mean SD. Student t test was used for continuous data. All P values of <.05 were considered statistically significant.
Results From 2006 through June 2011, a total of 18 patients met inclusion criteria (11 patients from The Children’s Hospital of Montefiore, 5 patients from The Morgan Stanley Children’s Hospital of New York, and 2 patients from Miami Children’s Hospital). The baseline demographics, clinical presentation, and management data on these 18 patients are summarized in the Table. Eleven of the 18 patients (61%) were overweight (BMI of 25-30) or obese (BMI >30). Clinical data is presented in the Table. Of the patients presenting with AF, 12 (67%) spontaneously terminated prior to cardioversion and 6 required synchronized cardioversion (33%). Four (22%) patients required intravenous medical ventricular rate control, all with diltiazem.9 All patients in this series had been admitted and were observed on continuous cardiac monitoring and none of the patients were noted to have EAT or other arrhythmias that could have been a trigger for AF. Seven patients (39%) were started on coumadin after cardioversion or spontaneous termination. Ten patients (56%) were placed on antiarrhythmic medications, with all initially placed on atenolol and 2 patients with recurrent AF that were both changed to sotalol and then to flecainide. A total of 7 patients (39%) were found to have an additional form of SVT that was reproducibly induced in the EP lab. The type of SVT in these 7 patients were: 5 typical AVNRT (71%) and 2 AVRT (29%). Eight patients (44%) had evidence for dual atrioventricular nodal physiology. In the patients with AVRT, both patients had concealed left sided accessory pathways, one in a left lateral position and
Table. Patients with lone AF (n = 18) Patient number
Age (y)
Weight (kg)
BMI
1 17 114 38 2 18 77 25 3 21 100 29 4 19 136 42 5 19 73 23 6 20 77 24 7 17 69 27 8 17 80 27 9 16 94 29 10 16 60 21 11 17 61 24 12 18 100 32 13 12 37 17 14 20 70 22 15 16 71 27 16 17 61 24 17 20 83 26 18 17 87 35 Total or mean 17.9 2.2 82 21 27 6
Total number Ventricular response of episodes rate in of AF AF (bpm) 1 1 1 1 1 1 2 2 5 2 2 5 3 4 1 1 1 1 1.5 1.0
200 111 150 93 120 110 160 170 60 120 105 90 170 120 70 123 40
CV or Spont?
Inducible SVT?
Type of SVT?
CV Spont Spont Spont Spont Spont Spont CV CV Spont Spont CV CV CV Spont Spont Spont Spont 12 Spont, 6 CV
Y N Y N N Y N N N Y N Y Y N Y N N N 7
AVNRT ORT AVNRT ORT AVNRT AVNRT AVNRT 5 AVNRT, 2 ORT
Successful Recurrence ablation? of AF? Y Y Y Y Y Y Y 7
N N N N N N N N Y N N N N Y N N N N 2
CV, cardioverted; N, no; ORT, orthodromic re-entry tachycardia; Spont, spontaneously terminated; Y, yes.
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April 2013 one in a left posterolateral position. All 7 patients (100%) underwent catheter ablation. Both of the left sided pathways were ablated via a trans-septal approach with RF. All of the patients with AVNRT underwent slow pathway ablation or modification with RF. One patient (patient 1) underwent an initial attempt with cryoablation with an 8 mm tip cryocatheter, but tachycardia remained inducible and then underwent successful slow pathway ablation with RF during the same procedure. An example of the 12 lead electrocardiogram at presentation and the inducible tachycardia found during EP study on patient 1 is shown in the Figure. There were no significant complications in any of the 18 patients who underwent formal EP testing. None of the patients had inducible sustained AF or required cardioversion for AF during the EP study. There was no statistically significant difference between the group with inducible SVT compared with the group with no inducible SVT with regard to age, BMI, or number of episodes of AF.
ORIGINAL ARTICLES The patients have been followed for a mean of 1.7 1.5 years. None of the 7 patients who underwent an ablation had a recurrence of AF or SVT at most recent follow-up. There were 2 patients (patients 9 and 14) who had no additional inducible SVT at EP study who had had several episodes of recurrent AF after the initial EP study. One is currently well controlled with no recurrences on oral flecainide, and the other has had several recurrences on oral flecainide.
Discussion This investigation has demonstrated that 39% of children and adolescents with lone AF had an additional form of SVT discovered during formal EP testing. Additionally, a large percentage of the patients with AF in this study were overweight or obese adolescent males. Those patients that underwent catheter ablation had no recurrences of AF, or SVT, at medium-term follow-up. Though this study
Figure. A, Twelve lead electrocardiogram of patient 1 presenting with AF and rapid ventricular response. B, Finding on EP study of easily and repeatedly inducible AVNRT. The patient underwent successful RF slow pathway ablation. Lone Atrial Fibrillation in the Young – Perhaps Not So “Lone”?
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does not prove that the inducible SVT in these patients was the definite trigger for AF and the overall patient numbers were small, the higher than expected percentage of patients with lone AF with inducible AVNRT and AVRT was notable. The initiation of AF in adults has been shown to be multifactorial.10 The etiologies include underlying cardiomyopathies, congenital heart disease (from atrial scars from atrial incisions at the time of surgery, atrial stretch, and/or sinus node dysfunction), alcohol, supplements and drugs of abuse, coffee, stress, electrical activation from the pulmonary veins, and genetic factors.11-15 In adults with structurally normal hearts, however, there are multiple reports on the concurrence of AF and SVT.3-5,7 In the adult population, in 1990 Hurwitz et al were one of the first groups to report on patients with AVNRT who were also noted to have AF as they had 3 patients with AVNRT who also had AF on transtelephonic monitoring.16 Sauer et al in 2006 reported on 629 adults who underwent EP study ablation for AF, and they found 4.3% had inducible sustained AVNRT.5 In that series, 13 had a slow-pathway modification for inducible AVNRT, but did not undergo pulmonary vein isolation, and the patients who underwent ablation for AVNRT were more likely to be free of AF at medium-term follow-up. Razavi et al hypothesized that slow-pathway ablation may also decrease the risk of AF because of the effect of ablation on vagal tone in the atrium.6 Sciara et al reported on 257 adults with AF and 26 (10%) had inducible SVT at EP study.17 The patients with SVT in that study were significantly younger than those without SVT. The etiology of AF in children and adolescents with a structurally normal heart is presently unclear. Though AF may be more frequently seen in children and adolescents with repaired, palliated, or unrepaired congenital heart disease, an underlying cardiomyopathy, rheumatic heart disease, Wolff-Parkinson-White syndrome, cardiac tumors, or neuromuscular disease, lone AF is quite rare in the pediatric population.18-20 In 2004, Nanthakumar et al published data on 9 adolescents with lone AF and found ectopic atrial foci from the pulmonary veins, left atrium, and crista terminalis were the nidus of AF initiation.21 Ablating the ectopic atrial foci in these patients was effective at preventing a recurrence of AF in 78% of these patients. Nasso et al performed an epicardial ablation and pulmonary vein isolation via a thoracotomy on a pediatric patient without the use of cardiopulmonary bypass with recurrent lone AF and evidence of macro-reentry via the pulmonary veins.22 Other small series and case reports in children with lone AF have suggested that AF may have been triggered after an episode of AVNRT or AVRT. Strieper et al reported 4 patients with lone AF with inducible other forms of tachycardia who underwent ablation for a re-entrant or automatic form of SVT.23 They concluded that EP study and ablation should be considered in the pediatric population for lone AF, but stressed that the adult strategy of pulmonary vein isolation should be avoided in these patients. It is striking that 61% of the patients were overweight or obese in our series. This high percentage of overweight or 830
Vol. 162, No. 4 obese patients is likely higher than would be seen in a random sampling of pediatric patients, as recent data has shown that up to 30% of the children and adolescents in the US are obese.17 Adult reports using the Framingham data have shown a link between obesity and new-onset AF.24 Possible etiologies for this association between obesity and AF include systemic hypertension, ventricular diastolic dysfunction, and left atrial enlargement. The relationship between obesity and lone AF in our series and in children and adolescents is unclear at present time and warrants further investigation. Though the overall patient numbers in this series are small, the notable number of patients with inducible SVT during formal EP testing (39%) is striking. If AF was triggered by SVT in these patients, ablation may help to prevent recurrences of both SVT and possibly AF. Our findings would lead us to conclude that formal EP study should be considered for young patients who present with lone AF. Standard AF ablation with pulmonary vein isolation, as is commonly performed in the adult population, may not be required in the pediatric population and in the opinion of the authors should be avoided. There are several limitations to this analysis. First, overall patient numbers were small (18 total patients). Though the majority of young patients presenting with lone AF at the 3 arrhythmia centers underwent formal EP study during the study period, it is unknown whether all patients that presented to all 3 arrhythmia centers underwent formal EP study, and this may, therefore, result in a selection and recruitment bias for the patients that underwent EP study. In addition, the presence of SVT in these patients does not prove that SVT was the trigger for AF. The abnormal tachycardia substrate in almost half of these patients, however, is a notable finding and would not be expected with a random cohort of patients with no prior history of SVT. Finally, conclusions about obesity in relation to lone AF need to be tempered by the small overall number of patients in this cohort. An EP study should be considered for pediatric patients presenting with lone AF to rule-out an additional cause of SVT that may trigger AF. Further study of the role of sex, obesity, and additional forms of SVT that could trigger AF in children and adolescents is warranted. n Submitted for publication May 21, 2012; last revision received Jul 18, 2012; accepted Sep 7, 2012. Reprint requests: Scott R. Ceresnak, MD, Pediatric Arrhythmia Service, Division of Pediatric Cardiology, The Children’s Hospital at Montefiore, Albert Einstein College of Medicine, 3415 Bainbridge Avenue, Rosenthal 1, Bronx, NY 10467-2490. E-mail: [email protected]
References 1. Sacchetti A, Moyer V, Baricella R, Cameron J, Moakes ME. Primary cardiac arrhythmias in children. Pediatr Emerg Care 1999;15:95-8. 2. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2011;123:e269-367.
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April 2013 3. Chang S-L, Tai C-T, Lin Y-J, Lo L-W, Tuan T-C, Udyavar AR, et al. Electrophysiological characteristics and catheter ablation in patients with paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 2008;19:367-73. 4. Amasyali B, Kose S, Aytemir K, Kilic A, Heper G, Kursaklioglu H, et al. Atrioventricular nodal reentrant tachycardia with paroxysmal atrial fibrillation: clinical and electrophysiological features and predictors of atrial fibrillation recurrence following elimination of atrioventricular nodal reentrant tachycardia. J Intervent Card Electrophysiol 2005;13:195-201. 5. Sauer WH, Alonso C, Zado E, Cooper JM, Lin D, Dixit S, et al. Atrioventricular nodal reentrant tachycardia in patients referred for atrial fibrillation ablation: response to ablation that incorporates slow-pathway modification. Circulation 2006;114:191-5. 6. Razavi M, Cheng J, Rasekh A, Yang D, Delapasse S, Ai T, et al. Slow pathway ablation decreases vulnerability to pacing-induced atrial fibrillation: possible role of vagal denervation. Pacing Clin Electrophysiol 2006;29:1234-9. 7. Katritsis DG, Giazitzoglou E, Wood MA, Shepard RK, Parvez B, Ellenbogen KA. Inducible supraventricular tachycardias in patients referred for catheter ablation of atrial fibrillation. Europace 2007;9:785-9. 8. Weiss R, Knight BP, Bahu M, Zivin A, Souza J, Goyal R, et al. Long-term follow-up after radiofrequency ablation of paroxysmal supraventricular tachycardia in patients with tachycardia-induced atrial fibrillation. Am J Cardiol 1997;80:1609-10. 9. Pass RH, Liberman L, Al-Fayaddh M, Flynn P, Hordof AJ. Continuous intravenous diltiazem infusion for short-term ventricular rate control in children. Am J Cardiol 2000;86:559-62. A9. 10. Korantzopoulos P, Liu T, Milionis HJ, Li G, Goudevenos JA. ‘Lone’ atrial fibrillation: hunting for the underlying causes and links. Int J Cardiol 2009;131:180-5. 11. Centurion OA, Shimizu A, Isomoto S, Konoe A. Mechanisms for the genesis of paroxysmal atrial fibrillation in the Wolff Parkinson-White syndrome: intrinsic atrial muscle vulnerability vs. electrophysiological properties of the accessory pathway. Europace 2008;10:294-302. 12. Krishnamoorthy S, Lip GYH, Lane DA. Alcohol and illicit drug use as precipitants of atrial fibrillation in young adults: a case series and literature review. Am J Med 2009;122:851-6.e3.
Lone Atrial Fibrillation in the Young – Perhaps Not So “Lone”?
ORIGINAL ARTICLES 13. Mattioli AV, Bonatti S, Zennaro M, Melotti R, Mattioli G. Effect of coffee consumption, lifestyle and acute life stress in the development of acute lone atrial fibrillation. J Cardiovasc Med 2008;9:794-8. 14. Roberts JD, Gollob MH. Impact of genetic discoveries on the classification of lone atrial fibrillation. J Am Coll Cardiol 2010;55:705-12. 15. Stiles MK, John B, Wong CX, Kuklik P, Brooks AG, Lau DH, et al. Paroxysmal lone atrial fibrillation is associated with an abnormal atrial substrate: characterizing the “second factor”. J Am Coll Cardiol 2009;53: 1182-91. 16. Hurwitz JL, German LD, Packer DL, Wharton JM, McCarthy EA, Wilkinson WE, et al. Occurrence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia due to atrioventricular nodal reentry. Pacing Clin Electrophysiol 1990;13:705-10. 17. Ogden CL. Prevalence of high body mass index in US children and adolescents, 2007-2008. JAMA 2010;303:242-9. 18. Hsu DT. Cardiac manifestations of neuromuscular disorders in children. Paediatr Respir Rev. 2010;11:35-8. 19. Brown ML, Dearani JA, Danielson GK, Cetta F, Connolly HM, Warnes CA, et al. Functional status after operation for Ebstein anomaly: the Mayo Clinic experience. J Am Coll Cardiol 2008;52:460-6. 20. Mainzer G, Khoury A, Gelernter-Yaniv L, Lorber A. Neonatal atrial fibrillation after surgical repair of tracheoesophageal fistula with esophageal atresia. Pediatr Cardiol 2008;29:150-2. 21. Nanthakumar K, Lau YR, Plumb VJ, Epstein AE, Kay GN. Electrophysiological findings in adolescents with atrial fibrillation who have structurally normal hearts. Circulation 2004;110:117-23. 22. Nasso G, Bonifazi R, Fiore F, Balducci G, Conte M, Lopriore V, et al. Minimally invasive epicardial ablation of lone atrial fibrillation in pediatric patient. Ann Thorac Surg 2010;90:e49-51. 23. Strieper MJ, Frias P, Fischbach P, Costello L, Campbell RM. Catheter ablation of primary supraventricular tachycardia substrate presenting as atrial fibrillation in adolescents. Congenital Heart Dis 2010;5:465-9. 24. Schoonderwoerd BA, Smit MD, Pen L, Van Gelder IC. New risk factors for atrial fibrillation: causes of ‘not-so-lone atrial fibrillation’. Europace 2008;10:668-73.
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Study design A multicenter review of patients with lone AF who underwent electrophysiology (EP) study from 2006-2011 was performed. Inclusion criteria: age #21 years, normal ventricular function, structurally normal heart, history of AF, and EP study and/or ablation performed. Exclusion criteria: congenital heart disease or cardiomyopathy. Patient demographics, findings at EP study and follow-up data were recorded. Results Eighteen patients met inclusion criteria. The mean age was 17.9 2.2 years, weight was 82 21 kg, body mass index was 27 6, and 15 (83%) were males. Eleven (61%) were overweight or obese. Seven (39%) had inducible SVT during EP study: 5 atrioventricular nodal re-entry tachycardia (71%) and 2 concealed accessory pathways with inducible atrioventricular re-entry tachycardia (29%). All 7 patients with inducible SVT underwent radiofrequency ablation. There were no complications during EP study and/or ablation for all 18 patients. The mean follow-up was 1.7 1.5 years and there were no recurrences in the 7 patients who underwent ablation. There were 2 recurrences of AF in patients with no other form of SVT during EP study. Conclusions Inducible SVT was found in 39% of pediatric patients undergoing EP study for lone AF. EP study should be considered for pediatric patients presenting with lone AF. (J Pediatr 2013;162:827-31).
L
one atrial fibrillation, or atrial fibrillation (AF) in patients with a structurally and functionally normal heart, is a rare dysrhythmia in children and adolescents. Although AF is common in the adult population, in young people it is rare in the absence of significant structural or congenital heart disease.1 Persistent or recurrent AF carries inherent risks and morbidities which include stroke, heart failure, and death.2 There are sporadic reports in the literature on patients who have other forms of supraventricular tachycardia (SVT), such as atrioventricular re-entry tachycardia (AVRT), atrioventricular nodal re-entry tachycardia (AVNRT), and ectopic atrial tachycardia (EAT), that may trigger AF and there are limited reports of ablation for these forms of SVT intended to prevent recurrence of AF.3-8 We sought to determine the frequency of additional forms of SVT in young people who present with lone AF. We hypothesized that young patients with lone AF may have additional forms of SVT (ie, AVRT, AVNRT, and EAT) that may be a trigger for AF. In addition, we theorize that electrophysiology (EP) study and ablation of their additional form of SVT may help prevent further recurrences of AF. Secondary aims of the study were to describe the clinical presentation, management, and patient outcomes of children and adolescents with lone AF.
Methods After approval was obtained by the Institutional Review Board, a multicenter retrospective analysis of patients who underwent EP testing and/or ablation due to a history of lone AF between 2006 and 2011 was performed. The data collected were obtained from three pediatric arrhythmia centers (The Children’s Hospital of Montefiore, The Morgan Stanley Children’s Hospital of New York, and Miami Children’s Hospital). In this investigation, lone AF was defined as a history of AF in the setting of a structurally and functionally normal heart with normal right and left ventricular size and function. The inclusion criteria were patients #21 years of age, with a history of lone AF, who underwent invasive EP testing and/or ablation. Patients with a history of structural or congenital heart disease, a prior history of cardiac surgery, a history of renal or pulmonary disease, or a prior history of EP study and/or ablation due to a known history of SVT or WolffFrom the Pediatric Arrhythmia Service, Division of Parkinson-White syndrome were excluded. Pediatric Cardiology, The Children’s Hospital at 1
AF AVNRT AVRT BMI EAT EP RF SVT
Atrial fibrillation Atrioventricular nodal re-entry tachycardia Atrioventricular re-entry tachycardia Body mass index Ectopic atrial tachycardia Electrophysiology Radiofrequency Supraventricular tachycardia
Montefiore, Albert Einstein College of Medicine, Bronx, NY; 2Division of Pediatric Cardiology, The Morgan Stanley Children’s Hospital, New York, NY; 3Division of Pediatric Cardiology, Department of Pediatrics, Miami Children’s Hospital, Miami, FL; and 4Pediatric Arrhythmia Service, Division of Pediatric Cardiology, Department of Pediatrics, Bronx, NY The authors declare no conflicts of interest. Portions of this study were presented at the Annual Scientific Session of the American College of Cardiology, March 25, 2012, in Chicago, IL. 0022-3476/$ - see front matter. Copyright ª 2013 Mosby Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2012.09.016
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The following data were obtained for each patient: demographic data (age, height, weight, sex), cardiac function and anatomy on echocardiography, urine toxicology screen at presentation, clinical presentation and management of AF, EP study and ablation findings, and follow-up data. Overweight was defined by a body mass index (BMI) of 25-30 and obese by a BMI >30. A clinically indicated EP study was performed on each patient after informed consent was obtained. Anti-arrhythmic medications were stopped at least 5 half-lives prior to the procedure and anti-coagulants were stopped at least 1 week prior. All patients underwent EP study at least 6 weeks after their initial presentation. Patients were given intravenous sedation or general anesthesia at the discretion of the physician performing the procedure. Patients underwent an initially limited EP study with 1 or 2 catheters placed via the right femoral vein with a catheter placed in the coronary sinus and the right ventricular apex or His and right ventricular apex. Standard atrial and ventricular pacing protocols were employed that were similar at each center, with rapid atrial pacing, up to double atrial extrastimulus testing, ventricular overdrive pacing, and single ventricular extrastimulus testing. Testing was repeated routinely with administration of intravenous isoproterenol in an attempt to induce SVT. Adenosine was routinely given during sinus rhythm and with ventricular pacing to help elucidate the presence or absence of an accessory pathway. If SVT was inducible, additional EP diagnostic catheters were then placed and an ablation was attempted. Radiofrequency (RF) energy was used as the first line tool for ablation with cryotherapy reserved for locations near the compact atrioventricular node at the discretion of the operator. Statistical Analyses Statistical analysis was performed using SPSS software (SPSS Inc, Chicago, Illinois). Categorical and dichotomous vari-
Vol. 162, No. 4 ables were expressed as percentages and continuous variables were expressed as mean SD. Student t test was used for continuous data. All P values of <.05 were considered statistically significant.
Results From 2006 through June 2011, a total of 18 patients met inclusion criteria (11 patients from The Children’s Hospital of Montefiore, 5 patients from The Morgan Stanley Children’s Hospital of New York, and 2 patients from Miami Children’s Hospital). The baseline demographics, clinical presentation, and management data on these 18 patients are summarized in the Table. Eleven of the 18 patients (61%) were overweight (BMI of 25-30) or obese (BMI >30). Clinical data is presented in the Table. Of the patients presenting with AF, 12 (67%) spontaneously terminated prior to cardioversion and 6 required synchronized cardioversion (33%). Four (22%) patients required intravenous medical ventricular rate control, all with diltiazem.9 All patients in this series had been admitted and were observed on continuous cardiac monitoring and none of the patients were noted to have EAT or other arrhythmias that could have been a trigger for AF. Seven patients (39%) were started on coumadin after cardioversion or spontaneous termination. Ten patients (56%) were placed on antiarrhythmic medications, with all initially placed on atenolol and 2 patients with recurrent AF that were both changed to sotalol and then to flecainide. A total of 7 patients (39%) were found to have an additional form of SVT that was reproducibly induced in the EP lab. The type of SVT in these 7 patients were: 5 typical AVNRT (71%) and 2 AVRT (29%). Eight patients (44%) had evidence for dual atrioventricular nodal physiology. In the patients with AVRT, both patients had concealed left sided accessory pathways, one in a left lateral position and
Table. Patients with lone AF (n = 18) Patient number
Age (y)
Weight (kg)
BMI
1 17 114 38 2 18 77 25 3 21 100 29 4 19 136 42 5 19 73 23 6 20 77 24 7 17 69 27 8 17 80 27 9 16 94 29 10 16 60 21 11 17 61 24 12 18 100 32 13 12 37 17 14 20 70 22 15 16 71 27 16 17 61 24 17 20 83 26 18 17 87 35 Total or mean 17.9 2.2 82 21 27 6
Total number Ventricular response of episodes rate in of AF AF (bpm) 1 1 1 1 1 1 2 2 5 2 2 5 3 4 1 1 1 1 1.5 1.0
200 111 150 93 120 110 160 170 60 120 105 90 170 120 70 123 40
CV or Spont?
Inducible SVT?
Type of SVT?
CV Spont Spont Spont Spont Spont Spont CV CV Spont Spont CV CV CV Spont Spont Spont Spont 12 Spont, 6 CV
Y N Y N N Y N N N Y N Y Y N Y N N N 7
AVNRT ORT AVNRT ORT AVNRT AVNRT AVNRT 5 AVNRT, 2 ORT
Successful Recurrence ablation? of AF? Y Y Y Y Y Y Y 7
N N N N N N N N Y N N N N Y N N N N 2
CV, cardioverted; N, no; ORT, orthodromic re-entry tachycardia; Spont, spontaneously terminated; Y, yes.
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April 2013 one in a left posterolateral position. All 7 patients (100%) underwent catheter ablation. Both of the left sided pathways were ablated via a trans-septal approach with RF. All of the patients with AVNRT underwent slow pathway ablation or modification with RF. One patient (patient 1) underwent an initial attempt with cryoablation with an 8 mm tip cryocatheter, but tachycardia remained inducible and then underwent successful slow pathway ablation with RF during the same procedure. An example of the 12 lead electrocardiogram at presentation and the inducible tachycardia found during EP study on patient 1 is shown in the Figure. There were no significant complications in any of the 18 patients who underwent formal EP testing. None of the patients had inducible sustained AF or required cardioversion for AF during the EP study. There was no statistically significant difference between the group with inducible SVT compared with the group with no inducible SVT with regard to age, BMI, or number of episodes of AF.
ORIGINAL ARTICLES The patients have been followed for a mean of 1.7 1.5 years. None of the 7 patients who underwent an ablation had a recurrence of AF or SVT at most recent follow-up. There were 2 patients (patients 9 and 14) who had no additional inducible SVT at EP study who had had several episodes of recurrent AF after the initial EP study. One is currently well controlled with no recurrences on oral flecainide, and the other has had several recurrences on oral flecainide.
Discussion This investigation has demonstrated that 39% of children and adolescents with lone AF had an additional form of SVT discovered during formal EP testing. Additionally, a large percentage of the patients with AF in this study were overweight or obese adolescent males. Those patients that underwent catheter ablation had no recurrences of AF, or SVT, at medium-term follow-up. Though this study
Figure. A, Twelve lead electrocardiogram of patient 1 presenting with AF and rapid ventricular response. B, Finding on EP study of easily and repeatedly inducible AVNRT. The patient underwent successful RF slow pathway ablation. Lone Atrial Fibrillation in the Young – Perhaps Not So “Lone”?
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does not prove that the inducible SVT in these patients was the definite trigger for AF and the overall patient numbers were small, the higher than expected percentage of patients with lone AF with inducible AVNRT and AVRT was notable. The initiation of AF in adults has been shown to be multifactorial.10 The etiologies include underlying cardiomyopathies, congenital heart disease (from atrial scars from atrial incisions at the time of surgery, atrial stretch, and/or sinus node dysfunction), alcohol, supplements and drugs of abuse, coffee, stress, electrical activation from the pulmonary veins, and genetic factors.11-15 In adults with structurally normal hearts, however, there are multiple reports on the concurrence of AF and SVT.3-5,7 In the adult population, in 1990 Hurwitz et al were one of the first groups to report on patients with AVNRT who were also noted to have AF as they had 3 patients with AVNRT who also had AF on transtelephonic monitoring.16 Sauer et al in 2006 reported on 629 adults who underwent EP study ablation for AF, and they found 4.3% had inducible sustained AVNRT.5 In that series, 13 had a slow-pathway modification for inducible AVNRT, but did not undergo pulmonary vein isolation, and the patients who underwent ablation for AVNRT were more likely to be free of AF at medium-term follow-up. Razavi et al hypothesized that slow-pathway ablation may also decrease the risk of AF because of the effect of ablation on vagal tone in the atrium.6 Sciara et al reported on 257 adults with AF and 26 (10%) had inducible SVT at EP study.17 The patients with SVT in that study were significantly younger than those without SVT. The etiology of AF in children and adolescents with a structurally normal heart is presently unclear. Though AF may be more frequently seen in children and adolescents with repaired, palliated, or unrepaired congenital heart disease, an underlying cardiomyopathy, rheumatic heart disease, Wolff-Parkinson-White syndrome, cardiac tumors, or neuromuscular disease, lone AF is quite rare in the pediatric population.18-20 In 2004, Nanthakumar et al published data on 9 adolescents with lone AF and found ectopic atrial foci from the pulmonary veins, left atrium, and crista terminalis were the nidus of AF initiation.21 Ablating the ectopic atrial foci in these patients was effective at preventing a recurrence of AF in 78% of these patients. Nasso et al performed an epicardial ablation and pulmonary vein isolation via a thoracotomy on a pediatric patient without the use of cardiopulmonary bypass with recurrent lone AF and evidence of macro-reentry via the pulmonary veins.22 Other small series and case reports in children with lone AF have suggested that AF may have been triggered after an episode of AVNRT or AVRT. Strieper et al reported 4 patients with lone AF with inducible other forms of tachycardia who underwent ablation for a re-entrant or automatic form of SVT.23 They concluded that EP study and ablation should be considered in the pediatric population for lone AF, but stressed that the adult strategy of pulmonary vein isolation should be avoided in these patients. It is striking that 61% of the patients were overweight or obese in our series. This high percentage of overweight or 830
Vol. 162, No. 4 obese patients is likely higher than would be seen in a random sampling of pediatric patients, as recent data has shown that up to 30% of the children and adolescents in the US are obese.17 Adult reports using the Framingham data have shown a link between obesity and new-onset AF.24 Possible etiologies for this association between obesity and AF include systemic hypertension, ventricular diastolic dysfunction, and left atrial enlargement. The relationship between obesity and lone AF in our series and in children and adolescents is unclear at present time and warrants further investigation. Though the overall patient numbers in this series are small, the notable number of patients with inducible SVT during formal EP testing (39%) is striking. If AF was triggered by SVT in these patients, ablation may help to prevent recurrences of both SVT and possibly AF. Our findings would lead us to conclude that formal EP study should be considered for young patients who present with lone AF. Standard AF ablation with pulmonary vein isolation, as is commonly performed in the adult population, may not be required in the pediatric population and in the opinion of the authors should be avoided. There are several limitations to this analysis. First, overall patient numbers were small (18 total patients). Though the majority of young patients presenting with lone AF at the 3 arrhythmia centers underwent formal EP study during the study period, it is unknown whether all patients that presented to all 3 arrhythmia centers underwent formal EP study, and this may, therefore, result in a selection and recruitment bias for the patients that underwent EP study. In addition, the presence of SVT in these patients does not prove that SVT was the trigger for AF. The abnormal tachycardia substrate in almost half of these patients, however, is a notable finding and would not be expected with a random cohort of patients with no prior history of SVT. Finally, conclusions about obesity in relation to lone AF need to be tempered by the small overall number of patients in this cohort. An EP study should be considered for pediatric patients presenting with lone AF to rule-out an additional cause of SVT that may trigger AF. Further study of the role of sex, obesity, and additional forms of SVT that could trigger AF in children and adolescents is warranted. n Submitted for publication May 21, 2012; last revision received Jul 18, 2012; accepted Sep 7, 2012. Reprint requests: Scott R. Ceresnak, MD, Pediatric Arrhythmia Service, Division of Pediatric Cardiology, The Children’s Hospital at Montefiore, Albert Einstein College of Medicine, 3415 Bainbridge Avenue, Rosenthal 1, Bronx, NY 10467-2490. E-mail: [email protected]
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