Author + information
- Received October 2, 2017
- Revision received February 6, 2018
- Accepted February 7, 2018
- Published online May 21, 2018.
- Matthew L. Furst, MDa,
- Elizabeth V. Saarel, MDa,
- Ayman A. Hussein, MDb,
- Oussama M. Wazni, MDb,
- Patrick Tchou, MDb,
- Mohamed Kanj, MDb,
- Walid I. Saliba, MDb and
- Peter F. Aziz, MDa,∗ ()
- aDepartment of Pediatric Cardiology, Cleveland Clinic, Cleveland, Ohio
- bRobert and Suzanne Tomsich Department of Cardiovascular Medicine, Cleveland Clinic, Sydell and Arnold Miller Heart & Vascular Institute, Cleveland, Ohio
- ↵∗Address for correspondence:
Dr. Peter F. Aziz, Department of Pediatric Cardiology, Cleveland Clinic, Mail Code M41, 9500 Euclid Avenue, Cleveland, Ohio 44195.
Objectives The goal of this study was to describe the clinical characteristics of pediatric patients with lone atrial fibrillation (LAF) and their treatment outcomes. The authors focused on patients who underwent ablation and compared the recurrence after ablation of supraventricular tachycardia substrates as presumed triggers versus pulmonary vein isolation (PVI).
Background LAF in pediatrics is rare, and outcomes remain poorly defined. Current guidelines on ablation are based on a few small studies, and we present outcomes from the largest cohort of patients after ablation.
Methods This retrospective review included patients ≤21 years of age diagnosed with LAF from 2004 to 2015. Relevant clinical data, including recurrence rates after treatment, were tracked and analyzed with a focus on patients who underwent ablation procedures.
Results Sixty-two patients were identified with LAF; 88% were male, and 63% were athletes. Of the 33 patients taking antiarrhythmic medication, 20 (61%) experienced recurrence. Overall, 16 patients (26%) underwent ablation: PVI in 10 (62.5%), ablation of an accessory pathway in 3 (19%), and modification of the slow atrioventricular nodal pathway in 3 (19%). One-half of patients who underwent PVI experienced documented recurrence. Of those who solely underwent supraventricular tachycardia substrate ablation, one-half also had symptomatic or documented recurrence.
Conclusions Ablation recurrence within this pediatric cohort was higher than expected. These recurrence rates may be demonstrative of the technical challenge of pediatric ablation compared with adult counterparts, characteristics of these patients such as athletic conditioning, or inherent differences in their atrial tissue, rendering it more refractory to substrate modification.
- atrioventricular nodal re-entrant tachycardia
- atrioventricular re-entrant tachycardia
- lone atrial fibrillation
- pulmonary vein isolation
Atrial fibrillation (AF) is the most common chronic arrhythmia in the adult population but is rarely encountered in the pediatric population (1). For this reason, few data exist on effective treatment strategies, including ablation, for AF in children. In the pediatric population, AF has been associated with comorbidities such as cardiomyopathy, structural heart disease, rheumatic heart disease, and thyroid disease; however, a small percentage of patients without structural or functional heart disease have isolated or lone atrial fibrillation (LAF) (2,3). Recently, obesity has also been identified as a risk factor for LAF in children as it is in adults, but otherwise the natural history and management of AF are not well described in pediatrics (4).
For adult patients, pulmonary vein isolation (PVI) by catheter ablation has emerged as a mainstay of treatment for paroxysmal AF (5,6). Studies indicate that a significant percentage of pediatric cases have a substrate of re-entrant supraventricular tachycardia (SVT), which is believed to act as a trigger for AF. Ablation of these substrates is an effective treatment for AF in some cases (7). There have also been a few reports of PVI being used in adolescents with medically refractory LAF with low rates of recurrence (8–10). The most recent guidelines on ablation in adolescents with structurally normal hearts state a Class IIb (with a Level of Evidence: C) recommendation for rare consideration of PVI in adolescents with recurrent, medically refractory AF requiring repeated DC cardioversion (11). The committee clearly states the need for more evidence in this area.
The present study reports our medical and interventional experience with management of AF in the largest series of pediatric patients treated at a single center thus far.
After approval was obtained from the Cleveland Clinic Institutional Review Board, we retrospectively identified a cohort of patients who were ≤21 years of age at time of presentation with documented AF diagnosed by using electrocardiogram (ECG), rhythm strip, or ambulatory event monitor with active medical records from December 2004 to December 2015. Patients with hemodynamically significant congenital heart disease requiring surgery, cardiomyopathy, history of renal or pulmonary disease, or known thyroid disease were excluded from the cohort. We also excluded patients with Wolff-Parkinson-White syndrome because these patients have a higher rate of AF than the general population (12).
Definitions and data collection
Study data were collected from our institutional database, EP Lab Database (version 1.3.41), and managed by using the REDCap electronic database capture tools hosted at the Cleveland Clinic. The diagnosis of AF was based on the capture of irregular rhythm in the absence of atrioventricular block, with narrow QRS complexes and no discernible P waves on ECG or rhythm strip, per the most recent guidelines. The AF episode should last long enough to be captured on ECG or at least 30 s on rhythm strip (5).
Medical records were reviewed for the collection of demographic data on each patient. Patients’ family history of AF, drug/alcohol use, stimulant medication and/or caffeine use, athletic status, and precipitating factors for an episode of AF were collected as patient variables. Clinical features, including presenting symptoms of AF, baseline heart rate, and heart rate during AF, were collected when available in the medical record. Baseline heart rate was collected as the heart rate closest in time to the patient’s episode of AF, either before or after. The patient’s medical management was followed, including prescribed medications, the maximum number of daily medications prescribed, whether a pill-in-pocket method was used, and the use of anticoagulant agents; also followed was the response to noninvasive management strategies such as recurrence of symptoms, documented AF recurrence while on medications, and the use and success of electrical cardioversion. In addition, for patients who underwent an electrophysiological study (EPS) and ablation procedure, electrophysiological and outcome data were collected.
Patients were retrospectively divided into those who had an ablation procedure and those who did not. Ablations were performed by various electrophysiologists both in the Pediatric Institute and the Heart and Vascular Institute of the Cleveland Clinic. Informed consent was obtained from the parents/guardians before EPS and the ablation procedures were performed. Antiarrhythmic medications were held for a minimum of 5 half-lives before the patient presented to the electrophysiology laboratory, and no patients were on amiodarone before the study. Testing for SVT substrates was performed in all patients during EPS by using standard techniques. Transseptal puncture was used when necessary to reach the left atrium for mapping and ablation. Mapping was performed by using a loop mapping catheter and Biosense Webster Carto (Biosense Webster, Diamond Bar, California) system. Radiofrequency ablation or cryoablation was used to eliminate accessory pathways, modify the atrioventricular slow pathway, and perform PVI with pulmonary vein antrum isolation guided by a Lasso NAV catheter (Biosense Webster).
Because this study spanned an 11-year period with the inclusion of multiple providers having performed ablation procedures, we found that the technique for PVI changed slightly over the course of the study. In the earlier years, the typical approach was to perform PVI, posterior wall ablation, and superior vena cava (SVC) ablation in the absence of phrenic nerve vcapture in most patients. More currently, PVI still includes extension sets septal from the right pulmonary veins; however, SVC ablation is reserved for redo cases. The most current AF ablation protocol for PVI uses standard mapping techniques and has been detailed previously in the literature (13). For the cases in which PVI was performed, additional areas were tested and ablated at the discretion of the electrophysiologist if fractionated or complex rapid electrograms, continuous electrical activity, or local gradients of activation were present.
After the initial ablation, these patients were observed for recurrence of AF. Arrhythmia recurrence in patients who had undergone PVI was defined according to previously published standards, which include capture of an atrial arrhythmia lasting at least 30 s by 12-lead ECG, event monitor, or Holter monitor with or without symptoms. AF episodes that occurred during a blanking period of 3 months after PVI were not considered to be recurrences (14). For those who underwent a non-PVI ablation of an SVT substrate, we did not factor in a blanking period. No implantable event monitors were utilized for surveillance.
Data were described by using medians and quartiles for continuous variables and counts and percentages for categorical variables. Demographic and clinical characteristics were compared by using Kruskal-Wallis tests for continuous characteristics and Pearson’s chi-square and Fisher exact tests for categorical characteristics. Sample sizes for individual variables reflect missing data. All analyses were performed on a complete-case basis. All tests were 2-tailed and performed at a significance level of 0.05. SAS version 9.4 software (SAS Institute, Inc., Cary, North Carolina) was used for all analyses.
Demographic and clinical characteristics
From December 2004 to December 2015, 62 patients met the study inclusion criteria with a median age of 17.6 years (1st, 3rd quartile: 16, 19 years) at the time of diagnosis of AF. None of these patients qualified as having persistent AF as defined by the most recent guidelines (5). The median length of follow-up for all patients was 6.4 months (1st, 3rd quartile: 0.16, 22.6 months). There was no statistical difference in any basic demographic data between the patients who had ablation and those who did not, including their age, sex, body mass index, family history of AF, or athletic status (Table 1). The youngest age at diagnosis was 13 years. The mean body mass index of our cohort was 26.7 kg/m2 (25th, 75th percentile: 22.3, 29.15), with 2 outliers with much higher body mass indices of 44.1 and 46.8 kg/m2. There was a predominance of male subjects in the study cohort (55 [89%] of the 62 patients). A large percentage (21%) of our patients had a family history of AF, although a positive family history was not associated with an increased likelihood of undergoing ablation (p = 0.77).
The majority of the cohort (63%) were athletes, and a high percentage participated in isometric exercise, including 21% who weightlifted and 29% who played football, which presumably involves isometric training. Overall, precipitating factors for AF were identified in 33 (51%) patients in the cohort, with the most common being exercise (19%), vasovagal mechanism (11%), or alcohol use (10%). In addition, 1 patient had her sole episode of AF associated with childbirth, which was categorized as vasovagal in nature. Two patients experienced AF after heavy blows to the chest during motor vehicle accidents, and one of these patients continued to have documented AF recurrence after that instigating event.
All but 2 patients had echocardiograms performed at our institution; those who did not have an echocardiogram had no physical examination or other findings consistent with congenital or acquired heart disease, and both had normal anatomy according to echocardiogram performed at an outside institution. Of those who had echocardiograms, all but 3 demonstrated completely normal anatomy. Those 3 patients had hemodynamically insignificant, minor congenital anomalies, including 2 with bicuspid aortic valves (with no aortic stenosis or regurgitation) and 1 with a persistent left SVC to the coronary sinus. These defects are common in the general population and have not been associated with AF.
Patients presented with a variety of symptoms, including palpitations in the majority (81%), shortness of breath in 39%, lightheadedness/dizziness in 24%, and syncope in 10%. Other symptoms included chest pain, fatigue, and emesis, with only 7% of patients found to be in AF incidentally without symptoms. There was no statistical difference between those patients who eventually underwent ablation and those who did not in terms of their presenting symptoms (Table 1). The maximum ventricular rate while in AF was documented for 10 of the 16 patients who underwent ablation and 33 of the 46 who did not undergo ablation, with averages of 134 and 127 beats/min, respectively; there was no statistically significant difference between the groups (p = 0.83).
Of the 62 patients in the study cohort, 7 (11%) were prescribed daily medical therapy after their first episode of AF, with no documented recurrence; 1 was started on a pill-in-the pocket method with no recurrence; and 41 (66%) were observed until experiencing recurrence of symptoms or documented AF (Figure 1). Daily medical therapy was prescribed for 33 patients (53%); of those, 79% were given a single medication, with the remainder of the patients eventually prescribed dual medical therapy. Nine patients were advised to use the pill-in-pocket method only, and an additional 6 patients, who were taking daily medication, were advised to use the pill-in-pocket method if they experienced symptoms of AF. The 4 medications used for the pill-in-pocket method included flecainide in 8 patients, metoprolol in 5 patients, propafenone in 5 patients, and diltiazem in 2 patients. Of the 33 patients receiving daily medication, 20 (61%) experienced recurrence of symptoms or had documented AF. Of these patients, 14 went on to have an ablation. The only statistically significant difference between the ablation and nonablation groups was taking daily medication (p = 0.001) (Table 1).
Anticoagulation use was variable and dependent on provider preference, with 40% of the overall cohort prescribed long-term medication for this purpose. A higher percentage (63%) of those who underwent ablation were undergoing long-term anticoagulation therapy than those who did not undergo ablation (36%). The most common anticoagulant used was aspirin in 17 patients, followed by warfarin in 8 patients, dabigatran in 3 patients, and apixaban in 1 patient. In this cohort, 24% of patients underwent electrical cardioversion at some point while in AF, with successful conversion to normal sinus rhythm in all cases. There was 1 patient with a particularly high burden of AF who required multiple cardioversions while in the emergency department, until eventually remaining in normal sinus rhythm.
Of the 62 total patients with AF, 16 (26%) underwent catheter ablation at an average age of 17 ± 2 years (Table 2). The median time of follow-up for these patients was 7.5 months (1st, 3rd quartile: 3.2, 15.7 months). Ten of these patients underwent PVI, and the other 6 had ablation of an SVT substrate discovered at the time of EPS. The most common reason for a patient to have undergone EPS with ablation was recurrence of symptoms or documented AF despite taking daily medication; this scenario occurred in 10 (63%) of the 16 patients. Five patients underwent EPS and ablation due to clinical suspicion for a re-entrant substrate and one due to the patient’s preference over chronic, daily medication. One of the 5 patients who underwent EPS for suspicion of SVT substrate did not have inducible SVT during EPS and instead underwent PVI. During the initial EPS and ablation procedures, isoproterenol was used at the physicians’ discretion in 67% of cases, and AF was inducible in 47% of patients.
All but one of the PVI procedures were performed with radiofrequency energy; the remaining procedure was performed by using a cryoballoon. Of the patients undergoing PVI, all but 1 underwent isolation of all 4 pulmonary veins. The patient who did not undergo this procedure had isolation of only the left pulmonary veins with no inducible AF or atrial premature contractions after the ablation while taking isoproterenol. In addition, 5 (50%) of these patients underwent SVC isolation, and 1 also underwent a line of ablation from the region of the lateral crista terminalis at the level of the upper tricuspid valve annulus to the inferior vena cava to isolate fractionated potentials in those areas. Overall, isoproterenol was used in 70% of the PVI cases for post-ablation testing to confirm lack of triggers.
Other forms of SVT induced during EPS included atrioventricular re-entrant tachycardia (AVRT) in 3 patients, atrioventricular nodal re-entrant tachycardia (AVNRT) in 3 patients, and ectopic atrial tachycardia in 2 patients. Accessory pathway ablation was performed in all 3 patients with inducible AVRT, and slow pathway modification was performed in the 3 patients with inducible AVNRT. The locations of the accessory pathways were 1 in each of the following areas: posteroseptal along the mitral annulus, anteroseptal along the tricuspid annulus, posterioseptal along the tricuspid annulus, and left free wall.
After the initial PVI procedure, 5 of the 10 patients experienced AF recurrence according to the predetermined definitions with capture of the events by ECG, Holter, or event monitor beyond the blanking period of 3 months (Figure 2). The median time from ablation to recurrence in these patients undergoing PVI was 13.4 months. Of those with recurrence, 3 patients had had isoproterenol testing after initial ablation, and 2 patients had not. Three patients underwent repeat PVI by radiofrequency ablation, and all were acutely successful. In 2 of these patients, all 4 pulmonary veins were re-isolated, and an additional line from the lateral crista terminalis to the inferior vena cava was performed. In Patient #12, an SVC to the right atrial line was also done. In Patient #13, the right upper and both lower pulmonary veins demonstrated recovery of conduction and were re-isolated in addition to the lateral crista to the inferior vena cava and SVC to the right atrial lines. Isoproterenol infusion was only used in 1 of the patients with re-isolation of all 4 veins but not in the other 2 veins. After redo ablation, Patient #13 continued to experience recurrence of atrial arrhythmias, captured on emergency department telemetry, prompting a third ablation procedure, during which bilateral superior pulmonary veins were again isolated. Despite repeat ablation, he continued to have symptoms at last follow-up while taking daily sotalol.
Of the patients who had an SVT substrate for AF and underwent ablation, 3 experienced symptoms consistent with their previous episodes of AF; however, either due to the transient nature of the episodes or the efficacy of the pill-in-pocket methods, 2 of these were not definitively confirmed by ECG or event monitor. Both of these patients experienced multiple episodes of palpitations that were consistent with prior AF, but both were lost to follow-up after report of these symptoms. Of the 3 patients who had recurrence of symptoms after ablation of an SVT substrate, 2 experienced those symptoms well outside of the 3-month “blanking period” typically observed in adults after ablation. The other patient, who underwent an accessory pathway ablation, had recurrence of symptoms shortly after the procedure at about 18 days later. No patients experienced complications from the ablation technique during follow-up.
Clinical characteristics and natural history
AF in children is more commonly associated with congenital heart disease, cardiomyopathy, and, in the past, rheumatic heart disease. Previously, within a cohort of 35 children with AF, only 1 patient had idiopathic paroxysmal AF (3). In a study of 320 patients with primary pediatric arrhythmias presenting to the emergency department, only 4.5% were found to have AF. This study also revealed a bimodal distribution of AF incidence according to age, with the highest percentage of children falling into the <1 year and 13- to 18-year-old groups (15). Within our population, the youngest to be diagnosed with LAF was 13 years old; the study median age was 18 years. Previous studies have questioned the diagnosis of AF in patients <1 year of age considering that the overall median age of onset is much older (41 years) (2).
Prolonged athletic training has been associated with an increased incidence of AF in otherwise healthy patients (16). Athletes are believed to have the substrate, modulators, and triggers for the development of AF (17,18). Increased vagal tone in young athletes is thought to be a primary mechanism. Parasympathetic activation causes heterogeneous shortening of atrial action potential duration and refractoriness, which then leads to a greater likelihood of atrial reentry (19). Our study showed that a high percentage of patients were competitive athletes. Most of our patients also experienced the onset of AF symptoms during exercise, indicating a possible stronger influence of the sympathetic system in arrhythmia onset. One study has shown that those patients with adrenergically induced AF were younger than those with vagal-mediated AF (20). Interestingly, a higher percentage of our patients performed isometric exercise in the form of weightlifting, either independently or as training for another sport such as football or baseball, which is counter to most studies on adults that show endurance training as a higher risk factor. One study demonstrated a very similar percentage of patients with LAF as having participated in sports. They also found that only current sport practice was associated with increased risk for AF, which was consistent with previous studies that showed a reduction in risk after cessation of practice (21,22).
Alcohol use, both on a long-term basis and in an acute binging setting, has been described as an independent risk factor for the development of AF, believed to be due to similar mechanisms as vagal-induced AF (23,24). Our study corroborated the findings of Mills et al. (25) in that we had 6 patients develop AF after an episode of alcohol use, most of which experienced their own episode of AF after drinking. The most common trigger in our cohort was exercise, and the vast majority of these patients had symptoms during rather than after activity, which is similar to findings in other studies (22).
As with previous studies (7,25), the present study had a predominance of male patients with LAF. In addition, we found that 21% of our cohort had a positive family history, which is comparable to earlier studies (25–27). It has been previously reported that the recurrence rate of AF in children is approximately 30%, and this study further showed that among those prescribed daily medical therapy, the recurrence rate is high at about two-thirds (4,25). The heritability of AF has been established in large studies such as from Framingham; however, we still do not have a full understanding of pathophysiology of AF in the young (28). As our understanding of the genetic basis for AF continues to advance, we may also understand the pathologic alterations that occur within the atria which cause this arrhythmia. We will likely be able to link certain gene variants with early-onset AF and better understand how the identified risk factors in fact lead to the development of AF. Studies on the genetic basis for early-onset AF have identified at least 14 rare genetic variants with as high as a 15% incidence in patients <40 years of age with LAF (29,30). Discoveries in the genetic basis for AF will particularly influence the management of the pediatric population in which many of the traditional risk factors are not yet present and traditional therapy does not seem to be as effective. A prior study (25) has demonstrated a high LAF recurrence rate in children with 4 of 40 patients diagnosed with persistent AF and 39% of the remainder having recurrence within a median follow-up of 12.5 months. This information corroborates a prospective study on adults by Pappone et al. (31), which also demonstrated a recurrence rate of 39% after an initial episode within 5 years of follow-up.
PVI has emerged as an effective treatment for AF in adults after the discovery that triggered activity originating from the myocardial sleeves within the pulmonary veins can initiate paroxysmal AF (32). In a meta-analysis of randomized clinical trials, the efficacy of PVI in adults was 77.8%, and ablation reduced the rate of AF recurrence by 71% in a combination of patients with paroxysmal and persistent AF (33). The etiology of AF in pediatrics, however, is not nearly as well studied, although the literature does indicate that a high percentage of patients have SVT substrates as triggers for AF (4,7,9). The efficacy of catheter ablation in pediatric patients with AF is also limited to a few small studies. Mills et al. (25) reported on a cohort of 42 pediatric patients with LAF, of whom 12 had an EPS and 6 underwent ablation. Their experience showed no recurrence in those who underwent PVI (n = 2) or other non-AF substrates except for atrial flutter, in which both had recurrence. There remain, however, no large population studies in pediatrics comparable to those conducted in adults to clearly define the long-term progression of this disease (25).
In a recent series of 4 teenaged male subjects with structurally normal hearts who underwent PVI, 2 patients had recurrence of AF after the initial ablation. After a second procedure, 1 patient had resolution of AF; however, the remaining patient continued to have recurrence and had a strong family history (8). In 2004, Nanthakumar et al. (10) demonstrated effective PVI in 78% of their 9 teenaged patients without recurrence over a mean follow-up period of 35 ± 22 months. The most recent consensus statement on the use of catheter ablation in pediatrics states a Class IIb recommendation for PVI in adolescents with medically refractory AF that has required repeated DC cardioversion, however, with only a Level of Evidence: C based on these limited previous studies (11). Our study reports on the largest number of pediatric patients having undergone ablation for AF and demonstrates a recurrence rate of 50% in the 10 patients who underwent PVI. Post-ablation testing with isoproterenol did not seem to aid with predicting recurrence. Of those patients who underwent a redo ablation due to captured recurrence, all 3 had repeat PVI, 1 of whom required a third ablation due to continued symptomatic AF recurrence. Although PVI may still be a reasonable approach for paroxysmal AF in children, this recurrence rate should be kept in mind and inform the expectations of practitioners. This finding also lends credence to the most recent guidelines on catheter ablation in children that clearly state that this procedure should be performed “only in exceptional cases” and performed only with the “direct assistance of a clinician experienced in the technique” due to the inherent risks in pediatric patients (11).
Hurwitz et al. (34) were among the first to show a correlation between AVNRT and AF in 3 adults, and this correlation has since been further reported in larger studies, such as from Sauer et al. (35), who described freedom of AF recurrence in 12 of 13 patients with slow pathway ablation alone. In a study of 18 teenaged patients, 39% had inducible SVT during the ablation procedure, and all of these patients underwent ablation of this substrate for AF. They exhibited no recurrence of AF over a median follow-up time of 1.7 ± 1.5 years. Based on promising results such as these, the current consensus statement gives a Class IIa recommendation for ablation in cases in which an SVT substrate is identified as the trigger for AF (11). Within our cohort, 38% of patients were found to have inducible SVT due to substrates for AVRT or AVNRT in the electrophysiology laboratory; this finding is almost identical to the percentages reported by Ceresnak et al. (7). Our cohort had findings different from previous studies, however, with an overall recurrence rate of 50% among those who underwent accessory pathway ablation and atrioventricular nodal slow pathway modification. Although not part of the current guidelines, an interesting question is whether pediatric patients having undergone ablation for AF should also automatically have an implantable device to better determine recurrence rather than depending on subjective symptoms in this age group. The utility of using this approach, however, would require further investigation.
The prevalence of AF increases with advancing age, from 3% in the population >60 years of age to nearly 9% in those >80 years of age (36). As high as 94% of ectopic foci that trigger AF in adults have been found to originate in the pulmonary veins (32). This study was performed at a large institution with a high volume of clinical experience with PVI as a mode of therapy for AF in adults. Although statistical significance could not be achieved due to low numbers, this study did demonstrate a 50% recurrence rate within our 10 patients. Considering that reconnection of pulmonary veins ultimately seemed to achieve elimination of symptoms in most patients who underwent PVI, perhaps this finding shows that these pediatric patients present more of a technical challenge than their adult counterparts or that there is a difference in their atrial tissue rendering it more refractory to initial ablation.
This study has inherent limitations of a retrospective, observational nature such as the inability to utilize more comprehensive protocols for follow-up. As with many pediatric studies on LAF, our cohort includes a small number of patients, from which it is difficult to extrapolate definitive conclusions about management strategies and their results.
Due to the difficulty of capturing transient AF events in patients not currently wearing a Holter or event monitor and those who had successful treatment with the pill-in-pocket method, it was difficult to definitively know whether some patients had true AF recurrence. The assumption was made in a few instances that symptoms experienced after SVT substrate ablation were indicative of AF recurrence, as this approach is the practice of our pediatric electrophysiology group. Another challenge in the pediatric group is their notoriously low compliance with daily medications; thus, recommendations by electrophysiology physicians for ablative therapy that were based on recurrence while on medications could be confounding.
The high rate of AF recurrence in our cohort could be due to a number of other confounding factors. The total incidence of LAF may be much higher in the general population, with only those patients with more severe symptoms presenting to our tertiary care department. These patients would be more likely to have recurrence of symptoms as well. Due to the retrospective nature of the study, questions regarding stimulant drug and caffeine use were inconsistently recorded. This lack of standardization for documentation also leads to insufficient data to answer questions pertaining to the selection criteria for re-ablation.
This cohort of pediatric patients with LAF had characteristics very similar to previous studies. A high percentage of our patients were athletes, with many performing isometric exercise. This study found a high recurrence rate, with nearly two-thirds of patients taking daily medication experiencing symptomatic AF recurrence. We also found that a high percentage of patients with documented AF had an SVT substrate, as has been previously reported. Ablation of these SVT substrates prevented AF symptom recurrence in only one-half of patients. PVI was also preventative of AF recurrence in only one-half of patients; however, due to the low number of patients in the cohort, we were unable to demonstrate this finding as a statistically significant difference from the adult population. Nevertheless, this recurrence rate does suggest that there may be difference between PVI performed in children and adults. Perhaps this difference is multifactorial, resulting from a combination of the increased technical difficulty of ablation in pediatric patients and intrinsic patient factors. These factors include a higher degree of athletic conditioning, particularly with isometric exercise and possible inherent differences in their atrial tissue, rendering it more refractory to substrate modification. Regardless of the reasons, our data are in agreement with the most recent guidelines that suggest conservative and rare utilization of PVI in pediatric patients with medically refractory AF at experienced centers.
COMPETENCY IN MEDICAL KNOWLEDGE: In this study of pediatric LAF, medical therapy proved ineffective in most cases. Furthermore, one-half of the patients who underwent PVI, as well as one-half who underwent SVT substrate modification, had recurrence of AF.
TRANSLATIONAL OUTLOOK: Major questions about the etiology of LAF in pediatric patients remain, which if answered may lead to a better understanding of their higher-than-expected recurrence rate despite medical and interventional treatment. We have only begun to explore the genetic basis for familial AF, although the growing evidence for a genetic predisposition for AF should prompt further research as well. The rarity of conditions such as LAF in the pediatric population makes it a challenge to study large numbers of patients in a prospective fashion at individual centers. Therefore, the next step in studying LAF in pediatrics will require a multicenter, prospective approach to better delineate the unique clinical characteristics of these patients and outcomes of both medical and interventional treatment strategies. Based on the findings of this study, our center is currently in the beginning stages of such a venture and plan to utilize the broader resources of the Pediatric and Congenital Electrophysiology Society.
The authors thank Sarah Worley, MS, Lu Wang, MS, and Anne Tang, MS, at the Cleveland Clinic, Section of Biostatistics, Quantitative Health Sciences/JJN-3, for statistical support.
Dr. Saliba has received speaker fees honoraria from Boston Scientific and Biosense Webster. All other authors have reported that they have no other 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
- atrial fibrillation
- atrioventricular nodal re-entrant tachycardia
- atrioventricular re-entrant tachycardia
- electrophysiology study
- lone atrial fibrillation
- pulmonary vein isolation
- superior vena cava
- supraventricular tachycardia
- Received October 2, 2017.
- Revision received February 6, 2018.
- Accepted February 7, 2018.
- 2018 American College of Cardiology Foundation
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