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Risk of atrial fibrillation according to the initial presentation of a preexcitation syndrome
International Journal of Cardiology 157 (2012) 359–363
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International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Risk of atrial fibrillation according to the initial presentation of a preexcitation syndrome Béatrice Brembilla-Perrot ⁎, Irina Popescu, Olivier Huttin, Pierre Yves Zinzius, Lucian Muresan, Soumaya Jarmouni, Ibrahim Nossier, Jérôme Schwartz, Jean Marc Sellal, Daniel Beurrier, Marius Andronache, Christian de Chillou, Olivier Selton, Pierre Louis, Arnaud Terrier de la Chaise Department of cardiology, University Hospital of Brabois, Vandoeuvre, France
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Article history: Received 29 November 2010 Accepted 21 December 2010 Available online 15 January 2011 Keywords: Atrial fibrillation Wolff–Parkinson–White syndrome Electrophysiology
a b s t r a c t Background: Atrioventricular reentrant tachycardia (AVRT) is frequent in Wolff–Parkinson–White syndrome (WPW). Atrial fibrillation (AF) is rare. The purpose of the study was to determine the factors of spontaneous AF in WPW according to the initial presentation. Methods and results: Electrophysiological study (EPS) was performed among 709 patients with a preexcitation syndrome. First event was AF in 44 patients. Remaining patients were studied for AVRT (314), syncope (94), adverse presentation without AF (9) or systematically (248 asymptomatic patients). Patients with AF were older than other patients (44 ± 16 years vs 34.5 ± 17) (0.0003); maximal rate conducted over accessory pathway (AP) was higher in patients with AF than in other patients except in adverse presentation (0.0002); AVRT was induced more frequently in patients with AF than in asymptomatic patients (57% vs 14.5%) but less than in patients with AVRT (89%). AF was induced more frequently in patients with AF than in other patients except in adverse presentation (b 0.0001). During follow-up AF occurred more frequently in patients with AF (5; 11%) than in patients with AVRT (7; 2%), with syncope (1%) and asymptomatic patients (4; 1.6%). Older age predicted recurrence (54 ± 16 vs 40 ± 17). Conclusions: AF was the first event in only 6% of patients with WPW and was a rare event in other patients. They are older but 10% are less than 18 years and have a more rapid conduction over AP than other patients. © 2011 Elsevier Ireland Ltd. All rights reserved.
Even if the Wolff–Parkinson–White syndrome (WPW) was first described in children and young patients with paroxysmal tachycardia, this syndrome can occur at any age. In most of the cases, a tachycardia with orthodromic reciprocal rhythm with a macroreentry circuit that uses the normal atrioventricular (AV) conduction system for the anterograde direction and the AV accessory pathway (AP) in the retrograde direction is the discovery mode. Flutter and atrial tachycardia's are rarely associated with WPW syndrome. The atrial arrhythmias are dominated by atrial fibrillation (AF) whose incidence has been estimated at 10–30% in the years preceding the AP's radiofrequency ablation and the systematic evaluation of preexcitation syndromes [1–7]. Most reports concern patients recruited before 1990. AF is usually clinically well-tolerated and may result in dizziness or fainting due to poor hemodynamic tolerance. Classically the incidence of paroxysmal AF is more common after 40 years with a male predominance. The potential severity of AF in WPW is the risk of degeneration into ventricular fibrillation (VF) in
⁎ Corresponding author. Cardiology, University Hospital of Brabois, 54500 Vandoeuvre Les Nancy, France. Tel.: +33 3 83 15 32 56; fax: +33 3 83 15 42 26. E-mail address: [email protected] (B. Brembilla-Perrot). 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.12.078
patients with short AP anterograde refractory period. The occurrence of VF may sometimes be the inaugural event [8–10]. The purpose of the study was to investigate the electrophysiological and clinical factors that might explain the occurrence of AF since 1990 and to evaluate the risk of AF occurrence in a population with a preexcitation syndrome according to the initial presentation.
1. Study population Seven hundred nine consecutive patients aged from 5 to 85 years (mean age 34.5 ± 17 years) were consecutively recruited in our centre during a period from 1990 to August 2010 for the diagnosis of an overt ventricular preexcitation syndrome. There were 429 men and 280 women. Associated heart disease was present in 5.5% of the population. The initial clinical presentation was as following: Forty four patients (6%), 31 men and 13 women, aged from 17 to 76 years with a mean age of 44 ± 16 years, presented with a documented spontaneous AF which was well-tolerated in 16 patients; adverse presentation defined as a documented life-threatening haemodynamically not tolerated arrhythmia, with collapse or
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Table 1 Clinical data (HD: heart disease).
Age Male gender HD
Total
AF
AVRT
Asymptomatic
Syncope
Adverse presentation
709
44
314
248
94
9
34 ± 16 429 (59%) 39 (5.5%)
44 ± 16*** 31 (70%) 5 (11%)
36 ± 16 181 (57%) 14 (4%)
32 ± 16 162 (65%) 16 (6%)
36 ± 18 48 (51%)* 4 (4%)
34 ± 22 7 (78%) 0
The upper line reports the groups of patients according to their initial presentation. *** p b 0.001 (comparison of the group with AF with remaining population and all subgroups). * p b 0.05: comparison of the group with AF with the group with syncope.
syncope and requiring a treatment in emergency was noted in 28 patients. Three hundred fourteen patients (44%) had a known history of paroxysmal reciprocal tachycardia. Two hundred forty eight patients (35%) were asymptomatic: ventricular preexcitation syndrome was discovered during a systematic assessment before anaesthesia, before sporting license, prior to employment in certain occupations at risk or on an ECG performed in the preventive medicine department or for a suspected congenital heart disease. Ninety four patients (13%) presented unexplained syncope without documentation of any arrhythmia, event that was generally the initial cause leading to discover the ventricular preexcitation syndrome. Nine patients have an adverse presentation related to a ventricular fibrillation (n = 4) or a rapid spontaneous antidromic tachycardia (n = 5). None of them had a documented AF. 2. Methods The data of electrophysiological study performed in these patients with a preexcitation syndrome were retrospectively analyzed. The electrophysiological study was performed either by intracardiac route in symptomatic patients or only by the transesophageal route (n = 275) in out-patient clinic when these patients were asymptomatic or had unexplained syncope. In these patients, there was no indication of ablation or the patients refused the procedure. The patients were not sedated. Informed consent was obtained from the patients and in the case of children, from children and their parents. Our protocol was previously reported [11–13]. Briefly, incremental atrial pacing was performed until the highest rate conducted 1/ 1 through the accessory pathway and/or the AV node. Programmed atrial stimulation at a basic cycle length of 600 and 400 ms with the introduction of one and two extrastimuli was performed. When a fast supraventricular tachycardia was induced, the protocol was stopped. In the absence of induction of a tachycardia conducted through the accessory pathway at a rate higher than 250 bpm, isoproterenol (0.02 to 1 μg min− 1) was then infused to increase the sinus rate to at least 130 bpm and the pacing protocol was repeated [14]. Arterial blood pressure was continuously monitored during the study by an external sphygmomanometer (Baxter, Japan). When EPS was performed by esophageal route, patients with induced atrial arrhythmias were monitored until sinus rhythm was restored. All patients were leaving hospital after electrophysiological study. Beta blockers were prescribed in patients with inducible re-entrant tachycardia. An association of class I antiarrhythmic drug (as flecainide) combined with small doses of beta blockers was preferred in patients with a malignant form of WPW syndrome until radiofrequency accessory pathway ablation was performed. The first ablations were currently performed in 1994 in our department. When the study was intracardiac, catheter ablation of accessory pathway was proposed during the same time to patients with induced rapid supraventricular
tachycardia and those with a spontaneous malignant form or malignant form according to electrophysiological criteria.
2.1. Definitions The accessory pathway's location was determined with the 12 lead ECG recorded in maximal preexcitation. The diagnosis of multiple accessory pathways was retained only if APs had different locations as left lateral and septal or right lateral and septal or left lateral and right lateral: in the left free wall location, the ablation could require the application of radiofrequency energy apparently at two sites, but it could be the same large accessory pathway. In the posteroseptal location left and right septal applications can be required to suppress the preexcitation. Sustained atrial fibrillation or reciprocating tachycardia was defined as a tachycardia that lasted more than one minute. Conduction over the accessory atrioventricular connection was evaluated by the measurement of the shortest atrial cycle length at which there was 1 to 1 conduction over the accessory connection and the shortest atrial tachycardia cycle length at which there was 1 to 1 conduction over the accessory connection. Wolff–Parkinson–White syndrome was considered as malignant at electrophysiology study and at risk of sudden death when the following association was observed: the maximal heart rate with a 1 to 1 conduction over the accessory pathway was more than 240 bpm in control state or more than 300 bpm after isoproterenol infusion [14] during induced sustained atrial fibrillation. Orthodromic tachycardia induction alone was not considered as a criterium for a high risk form of preexcitation syndrome. The preexcitation syndrome was considered as benign if no tachycardia was induced and a 1 to 1 conduction over accessory pathway (AP) was less than or equal to 240 bpm in control state and less than or equal to 300 bpm after isoproterenol was noted. Follow-up: patients were followed from 3 months to 20 years (mean 6 ± 4 years) by clinical evaluation and ECG recording at the last visit. After 1995, at the end of the electrophysiological study, ablation of accessory pathway was indicated in symptomatic patients or asymptomatic patients after detection of a potentially malignant form of the disease at electrophysiology. All patients in whom AP ablation was performed were seen one month after ablation and then every 1 or 2 years. Antiarrhythmic therapy with beta-blocker and/or flecainide was initiated when the patient refused the AP ablation or in case of failure of ablation. An indication of medical treatment was also used in small children and patients with anteroseptal AP in whom an involution of preexcitation can be expected [13]. Asymptomatic patients in whom there were no criteria of malignancy were not treated.
.2.1.1. Statistical analysis Data are expressed as means ± standard deviation (SD). For categorical variables the chi-squared test was performed. The independent-sample t test procedure was used for continuous variables. The stepwise logistic regression was used to analyse the relationships between presentation with AF (absence/presence = 0/1) as dependent variable and possible predictors (age, gender, accessory pathway location, the shortest cycle conducted through the accessory pathway, inducibility before and after isoproterenol) as independent variables. A p value b 0.05 was considered statistically significant. All statistical analyses were performed by using the SPSS package for Windows (version 17. 0.1, SPSS Inc, Chicago, Illinois).
Table 2 AP location (Septal location = right and left postero septal AP, anterosetal AP: other AP: right AP, Mahaim, undetermined location).
Left lateral Septal Other AP
Total
AF
AVRT
Asymptomatice
Syncope
Adverse presentation
709
44
314
248
94
9
278 (39%) 384 (54%) 47 (7%)
27(61%)*** 15 (34%)** 2 (4.5%)
154 (49%) 142 (45%) 18 (6%)
59 (24%) 166 (67%) 23 (9%)
33 (35%) 57 (61%) 4 (4%)
5 (55.5%) 4 (44.5%)
** p b 0.01, *** p b 0.001: comparison of the group with AF with remaining population.
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Table 3 Electrophysiological data; the left column reports the electrophysiological data (ATD = antidromic tachycardia; CS max HR = maximal heart rate in control state conducted 1 to 1 over AP; iso max HR: maximal heart rate conducted 1 to 1 over AP after isoproterenol, rapid AF: malignant form at electrophysiology, defined above).
AVRT AF ATD CS max HR Iso max HR Rapid AF
Total
AF
AVRT
Asymptomatice
Syncope
Adverse presentation
709
44
314
248
94
9
395 (56%) 153(21.5%) 50 (7%) 193 ± 63 241 ± 68 83 (12%)
25 (57%) 27(61%)*** 5 (11%) 237 ± 69*** 274 ± 78* 17 (39%)***
280 (89%) 54 (17%) 20 (6%) 192 ± 62 247 ± 68 22 (7%)
36 (14.5%) 42 (17%) 16 (6%) 184 ± 60 234 ± 69 22 (9%)
49 (54%) 24 (25.5%) 8 (8.5%) 189 ± 50 242 ± 69 16 (20%)
5 (55.5%) 6 (67%) 1 (12.5%) 283 ± 29 320 ± 29 6 (67%)
*p b 0.05, ** p b 0.01, *** p b 0.0001: comparison of the group with AF with remaining population.
3. Results 3.1. Clinical data of subjects with or without spontaneous AF at the initial presentation (Table 1) We observed the spontaneous occurrence of AF in some patients with conditions associated with increased sympathoadrenal stimulation like stress, emotional stress or surgery (n = 3), hyperthyroidism (n = 2), the postprandial state or the ingestion of alcohol (n = 14). The group of patients with documented spontaneous AF was older than other patients without spontaneous AF with a mean age of 44 ± 16 years versus an average of 34.5 ± 17 years in patients without AF (p 0.00032). The differences were significant with all subgroups, the patients with AVRT (p 0.035), the asymptomatic patients (p 0.02) and the patients with syncope (p 0.01). However the ages of patients with AF varied from 12 to 74 years. Five patients, 2 girls and 3 boys were younger than 18 years and all presented a poorly-tolerated AF with a feeling of dizziness and/or syncope. The percentage of male subjects tended to be higher in the AF group (70%) compared to other patients (59%) (NS 0.2). There was only a significant difference with the subgroup with syncope in which male gender was less frequent than in patients with AF (p 0.03). Regarding the location of the accessory pathway (Table 2), left lateral AP was more frequent than in total population (p 0.003) and septal AP less frequent (p 0.009). However, left lateral AP was as frequent as in patients with spontaneous AVRT, but more frequent than in asymptomatic patients (p b 0.001) or patients with syncope (p 0.003). Septal AP was as frequent as in patients with AVRT but less frequent than in asymptomatic (p 0.001) or patients with syncope (p 0.009). Other locations did not differ. Heart disease was rare in all subgroups and the incidence of associated heart disease did not differ significantly. There is only a trend for a higher incidence of heart disease in patients with AF than in patients with AVRT (p 0.08). 3.2. Data electrophysiological subjects with or without spontaneous AF at the initial presentation (Table 3) AVRT was induced with the same frequency as in total population and in the subgroup with syncope, but less frequently than in patients with spontaneous AVRT (p b 0.0001) and more frequently than in asymptomatic patients (p b 0.0001). The mean age of patients with
spontaneous AF and with inducible AVRT or without inducible AVRT was similar (respectively 43.5 ± 19 and 44 ± 16 years). AF was induced more frequently in patients with spontaneous AF than in total population and in all subgroups (p b 0.0001), except in patients with adverse presentation unrelated to AF. Antidromic tachycardia (ADT) was induced with the same frequency in all subgroups of patients. The maximal heart rate with a 1 to 1 conduction over the accessory pathway was higher in patients with AF than in total population either in control state (p 0.00012) or isoproterenol (p 0.04). When the subgroups are analysed, in control state, the rate was higher in patients with AF than in patients with AVRT (p 0.02) or in asymptomatic patients (p 0.007) and in patients with syncope (p 0.01); after isoproterenol, the rate was higher in patients with AF than in patients with AVRT (0.02) or asymptomatic patients (p 0.09); the differences were not significant in patients with syncope (0.09). However, the maximal heart rate with a 1 to 1 conduction over AP was lower in patients with AF than in patients with adverse presentation unrelated to AF, but the differences did not reach significance because of the small number of the last group (p 0.08) (Table 3). Potentially malignant forms at electrophysiology as defined above were more frequent in patients with AF than in all subgroups except in the subgroup with spontaneous adverse presentation (p b 0.0001). 3.3. Follow-up (3 months to 20 years; mean 6 ±4 years) (Table 4) AP radiofrequency was performed more frequently in patients with AF than in total population (p b 0.0001) and in group with syncope (p b 0.0001) or asymptomatic patients (p b 0.0001). The differences were not significant with patients with AVRT (0.06). The indications of ablation were as frequent as in patients with adverse presentation without AF. Five patients died: one of group with spontaneous AF who had electrophysiological signs of malignancy and who refused all treatments died suddenly; he had stopped all antiarrhythmic drugs and refused the ablation. One patient complaining only of AVRT died suddenly one month after AP ablation. The ablation was successful and without complications. One patient, 21 years old, complaining of recurrent and frequent AVRT's died just before AP ablation. He was studied at the age of 12 years and had signs of malignancy. He had stopped all antiarrhythmic drugs and had accepted the ablation but he died after a new AVRT just before admission. One patient, 70 years old,
Table 4 Follow-up.
Ablation AF
Total
AF
AVRT
Asymptomatice
Syncope
Adverse presentation
709
44
314
248
94
9
321 (45%) 14 (2%)
34 (77%)*** 5 (10%) ***
198 (63%) 5 (1.5%)
43 (17%) 4 (1.6%)
39 (41%) 2 (2%)
7 (78%)
The left column reports the number of patients treated by ablation of the accessory pathway and the number of patients who developed AF during the follow-up. *** p b 0.0001: comparison of the group with AF with remaining population, the group with syncope and asymptomatic group.
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with AVRT died after an important abdominal surgery and the cause of death remained unknown. One asymptomatic patient, 21 years old, died accidentally crushed by a tree. Only 2 of these 5 deaths were directly related to the preexcitation syndrome. Patients with spontaneous AF remained at high risk to have another AF despite AP ablation: recurrences of AF were noted in the group with spontaneous AF in 5 patients, 2 women and 3 men, despite AP ablation in 4 of them. Their age varied from 36 to 74 years (mean age 54 ± 16 years) and was significantly higher than in patients free of AF recurrences (40 ± 17 years) (p 0.028). All these patients had a permanent form of AF. Thirty of 34 (88%) patients of the group with spontaneous AF had no clinical recurrence of AF after ablation without antiarrhythmic drug. Remaining patients were treated by flecainide associated or not with betablockers. Permanent AF developed in 7 patients of the group with only AVRT despite AP ablation in 6 of them; their age varied from 48 to 55 years (mean 52 ± 4); when the 3 deaths are excluded, the frequency of AF is 7/311 (2.2%) that is lower than in the group with spontaneous AF (p b 0.002). One patient of group with syncope developed AF (1%). Among asymptomatic patients, 4 had AF. At the time of the first electrophysiological study, one patient 22 years old had no inducible AF or AVRT and developed a well-tolerated AF at the age of 36 years. Other patients had inducible AF and also a rapid conduction over AP, but they have not been treated. Mean age of these patients at the time of AF was 48.5 ± 18 years. Data of the second electrophysiological study were unchanged. These 4 patients developed a spontaneous AF with adverse presentation, between 3 and 14 years after initial evaluation [15]. AP ablation was performed after the occurrence of AF and the patients had no recurrences after ablation. Multivariate analysis indicated that the maximal rate conducted through the accessory pathway in control state, the induction of AF and age were independent significant predictors of spontaneous AF occurrence (respectively p b 0.0001, b0.0001, b0.01). Other data as gender, accessory pathway location, presence of a heart disease and AVRT induction were not significant. 4. Discussion The incidence of spontaneous documented AF as first event was low (6%) in a population with patent preexcitation syndrome. The risk of AF for asymptomatic patients, patients with spontaneous reentrant tachycardias or those with unexplained syncope was low and less than 2.5%. This incidence is lower than in studies reported more than 20 years ago [1–7]. AF has occurred since the age of 12 years, but the mean age of this population was higher than in remaining subjects. No other clinical finding was associated with AF development. On the other hand, electrophysiological factors of these patients differed from other patients: the AF induction was easy; the induction of AVRT was more frequent than in asymptomatic patients. More, the rate conducted 1 to 1 over AP was more rapid than in other patients. These electrophysiological data explained the higher frequency of malignant forms in this group. Some patients of the present study were recently reported, but clinical data of patients with spontaneous adverse events differed from those of patients presenting with AF [16]. The study of literature related a higher incidence of spontaneous AF from 10% to one third of patients with WPW syndrome [17–20] than in the present study. AF development is not usually associated with heart disease as confirmed in our study. Patients with WPW and obvious spontaneous AF seem to express a predominance of sympathetic activity with vagal inhibition [21,22]. Several hypotheses about initiation of spontaneous AF in patients with AP have been proposed for, such as spontaneous degeneration of an AVRT into AF, the conduction properties of the AP, the effect of the
AP on atrial architecture and the intrinsic atrial vulnerability [23]: the incidence of spontaneous degeneration of AVRT into AF was detected in 16–26% of cases with similar rates in patients with an obvious atrioventricular accessory pathway and those with a concealed AP [4,7]. It has previously been shown that reciprocal tachycardia may increase atrial vulnerability by reducing the length of the atrial cycle length and by increasing the sympathetic tone and atrial stretch due to hemodynamic changes which occurred during AVRT. During electrophysiological study the cycle length of induced AVRT was reported as significantly shorter in patients with AF compared to others, suggesting that more reciprocal tachycardia is rapid, more patient were likely to develop AF. This factor was not studied in our study. A short AP anterograde effective refractory period was found as discriminating in patients with and without spontaneous AF [4,6,7]. The short AP refractory period will be responsible for a rapid ventricular rate during AF associated with poor hemodynamic tolerance and hypoxia which will maintain the atrial arrhythmia. The results of the present study are consistent with the literature because patients with spontaneous AF were found to have a more rapid 1 to 1 conduction over AP than in other patients. During long term follow-up fewer patients will experience spontaneous AF after AP ablation with an incidence rate of recurrence of 6–10% [2,4,20]. However the risk of AF recurrence is higher in patients older than 50 years [24–26]. In the present study, AP ablation was performed in 45% of the patients with a preexcitation syndrome and this treatment is probably the cause of the risk reduction of AF in these patients; only 4 of 248 asymptomatic patients developed AF; 3 of them had inducible rapid AF and now would be systematically treated by AP ablation.
4.1. Study limitations The data associated with increased atrial vulnerability as the shortening of the atrial refractory period and the size of the left atrium on echocardiography are missing. The true incidence of spontaneous AF may be underestimated in our population because we could not take into account the spontaneous episodes of AF which are well-tolerated in patients considered as asymptomatic or the episodes of AF which could have terminated spontaneously before admission in patients with syncope, nor the possible spontaneous AF in patients with known history of reciprocal tachycardia. AF was only documented by ECG. Patient follow-up did not include a systematic Holter monitoring after ablation of the accessory pathway and post-ablation asymptomatic episodes of AF could have been ignored.
5. Conclusions Spontaneous atrial fibrillation in patients with a preexcitation syndrome was uncommon (6%). Patients with spontaneous AF were found to be older in our population, but it can occur in children. The presence of associated heart disease and the location of the accessory pathway were not predictive of atrial fibrillation occurrence. On the other hand, accessory pathway in patients with spontaneous AF had frequently rapid conduction properties and AF was frequently poorlytolerated. Despite of higher risk of AF recurrence than in other patients, 88% of patients who underwent an ablation of accessory pathway had no clinical recurrence of atrial fibrillation. The occurrence of AF in patients initially asymptomatic or presenting with re-entrant tachycardia or syncope was very rare. This lower incidence AF than in previous studies is probably explained by the indication of AP ablation in symptomatic patients and those with inducible supraventricular tachycardia.
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International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Risk of atrial fibrillation according to the initial presentation of a preexcitation syndrome Béatrice Brembilla-Perrot ⁎, Irina Popescu, Olivier Huttin, Pierre Yves Zinzius, Lucian Muresan, Soumaya Jarmouni, Ibrahim Nossier, Jérôme Schwartz, Jean Marc Sellal, Daniel Beurrier, Marius Andronache, Christian de Chillou, Olivier Selton, Pierre Louis, Arnaud Terrier de la Chaise Department of cardiology, University Hospital of Brabois, Vandoeuvre, France
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Article history: Received 29 November 2010 Accepted 21 December 2010 Available online 15 January 2011 Keywords: Atrial fibrillation Wolff–Parkinson–White syndrome Electrophysiology
a b s t r a c t Background: Atrioventricular reentrant tachycardia (AVRT) is frequent in Wolff–Parkinson–White syndrome (WPW). Atrial fibrillation (AF) is rare. The purpose of the study was to determine the factors of spontaneous AF in WPW according to the initial presentation. Methods and results: Electrophysiological study (EPS) was performed among 709 patients with a preexcitation syndrome. First event was AF in 44 patients. Remaining patients were studied for AVRT (314), syncope (94), adverse presentation without AF (9) or systematically (248 asymptomatic patients). Patients with AF were older than other patients (44 ± 16 years vs 34.5 ± 17) (0.0003); maximal rate conducted over accessory pathway (AP) was higher in patients with AF than in other patients except in adverse presentation (0.0002); AVRT was induced more frequently in patients with AF than in asymptomatic patients (57% vs 14.5%) but less than in patients with AVRT (89%). AF was induced more frequently in patients with AF than in other patients except in adverse presentation (b 0.0001). During follow-up AF occurred more frequently in patients with AF (5; 11%) than in patients with AVRT (7; 2%), with syncope (1%) and asymptomatic patients (4; 1.6%). Older age predicted recurrence (54 ± 16 vs 40 ± 17). Conclusions: AF was the first event in only 6% of patients with WPW and was a rare event in other patients. They are older but 10% are less than 18 years and have a more rapid conduction over AP than other patients. © 2011 Elsevier Ireland Ltd. All rights reserved.
Even if the Wolff–Parkinson–White syndrome (WPW) was first described in children and young patients with paroxysmal tachycardia, this syndrome can occur at any age. In most of the cases, a tachycardia with orthodromic reciprocal rhythm with a macroreentry circuit that uses the normal atrioventricular (AV) conduction system for the anterograde direction and the AV accessory pathway (AP) in the retrograde direction is the discovery mode. Flutter and atrial tachycardia's are rarely associated with WPW syndrome. The atrial arrhythmias are dominated by atrial fibrillation (AF) whose incidence has been estimated at 10–30% in the years preceding the AP's radiofrequency ablation and the systematic evaluation of preexcitation syndromes [1–7]. Most reports concern patients recruited before 1990. AF is usually clinically well-tolerated and may result in dizziness or fainting due to poor hemodynamic tolerance. Classically the incidence of paroxysmal AF is more common after 40 years with a male predominance. The potential severity of AF in WPW is the risk of degeneration into ventricular fibrillation (VF) in
⁎ Corresponding author. Cardiology, University Hospital of Brabois, 54500 Vandoeuvre Les Nancy, France. Tel.: +33 3 83 15 32 56; fax: +33 3 83 15 42 26. E-mail address: [email protected] (B. Brembilla-Perrot). 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.12.078
patients with short AP anterograde refractory period. The occurrence of VF may sometimes be the inaugural event [8–10]. The purpose of the study was to investigate the electrophysiological and clinical factors that might explain the occurrence of AF since 1990 and to evaluate the risk of AF occurrence in a population with a preexcitation syndrome according to the initial presentation.
1. Study population Seven hundred nine consecutive patients aged from 5 to 85 years (mean age 34.5 ± 17 years) were consecutively recruited in our centre during a period from 1990 to August 2010 for the diagnosis of an overt ventricular preexcitation syndrome. There were 429 men and 280 women. Associated heart disease was present in 5.5% of the population. The initial clinical presentation was as following: Forty four patients (6%), 31 men and 13 women, aged from 17 to 76 years with a mean age of 44 ± 16 years, presented with a documented spontaneous AF which was well-tolerated in 16 patients; adverse presentation defined as a documented life-threatening haemodynamically not tolerated arrhythmia, with collapse or
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Table 1 Clinical data (HD: heart disease).
Age Male gender HD
Total
AF
AVRT
Asymptomatic
Syncope
Adverse presentation
709
44
314
248
94
9
34 ± 16 429 (59%) 39 (5.5%)
44 ± 16*** 31 (70%) 5 (11%)
36 ± 16 181 (57%) 14 (4%)
32 ± 16 162 (65%) 16 (6%)
36 ± 18 48 (51%)* 4 (4%)
34 ± 22 7 (78%) 0
The upper line reports the groups of patients according to their initial presentation. *** p b 0.001 (comparison of the group with AF with remaining population and all subgroups). * p b 0.05: comparison of the group with AF with the group with syncope.
syncope and requiring a treatment in emergency was noted in 28 patients. Three hundred fourteen patients (44%) had a known history of paroxysmal reciprocal tachycardia. Two hundred forty eight patients (35%) were asymptomatic: ventricular preexcitation syndrome was discovered during a systematic assessment before anaesthesia, before sporting license, prior to employment in certain occupations at risk or on an ECG performed in the preventive medicine department or for a suspected congenital heart disease. Ninety four patients (13%) presented unexplained syncope without documentation of any arrhythmia, event that was generally the initial cause leading to discover the ventricular preexcitation syndrome. Nine patients have an adverse presentation related to a ventricular fibrillation (n = 4) or a rapid spontaneous antidromic tachycardia (n = 5). None of them had a documented AF. 2. Methods The data of electrophysiological study performed in these patients with a preexcitation syndrome were retrospectively analyzed. The electrophysiological study was performed either by intracardiac route in symptomatic patients or only by the transesophageal route (n = 275) in out-patient clinic when these patients were asymptomatic or had unexplained syncope. In these patients, there was no indication of ablation or the patients refused the procedure. The patients were not sedated. Informed consent was obtained from the patients and in the case of children, from children and their parents. Our protocol was previously reported [11–13]. Briefly, incremental atrial pacing was performed until the highest rate conducted 1/ 1 through the accessory pathway and/or the AV node. Programmed atrial stimulation at a basic cycle length of 600 and 400 ms with the introduction of one and two extrastimuli was performed. When a fast supraventricular tachycardia was induced, the protocol was stopped. In the absence of induction of a tachycardia conducted through the accessory pathway at a rate higher than 250 bpm, isoproterenol (0.02 to 1 μg min− 1) was then infused to increase the sinus rate to at least 130 bpm and the pacing protocol was repeated [14]. Arterial blood pressure was continuously monitored during the study by an external sphygmomanometer (Baxter, Japan). When EPS was performed by esophageal route, patients with induced atrial arrhythmias were monitored until sinus rhythm was restored. All patients were leaving hospital after electrophysiological study. Beta blockers were prescribed in patients with inducible re-entrant tachycardia. An association of class I antiarrhythmic drug (as flecainide) combined with small doses of beta blockers was preferred in patients with a malignant form of WPW syndrome until radiofrequency accessory pathway ablation was performed. The first ablations were currently performed in 1994 in our department. When the study was intracardiac, catheter ablation of accessory pathway was proposed during the same time to patients with induced rapid supraventricular
tachycardia and those with a spontaneous malignant form or malignant form according to electrophysiological criteria.
2.1. Definitions The accessory pathway's location was determined with the 12 lead ECG recorded in maximal preexcitation. The diagnosis of multiple accessory pathways was retained only if APs had different locations as left lateral and septal or right lateral and septal or left lateral and right lateral: in the left free wall location, the ablation could require the application of radiofrequency energy apparently at two sites, but it could be the same large accessory pathway. In the posteroseptal location left and right septal applications can be required to suppress the preexcitation. Sustained atrial fibrillation or reciprocating tachycardia was defined as a tachycardia that lasted more than one minute. Conduction over the accessory atrioventricular connection was evaluated by the measurement of the shortest atrial cycle length at which there was 1 to 1 conduction over the accessory connection and the shortest atrial tachycardia cycle length at which there was 1 to 1 conduction over the accessory connection. Wolff–Parkinson–White syndrome was considered as malignant at electrophysiology study and at risk of sudden death when the following association was observed: the maximal heart rate with a 1 to 1 conduction over the accessory pathway was more than 240 bpm in control state or more than 300 bpm after isoproterenol infusion [14] during induced sustained atrial fibrillation. Orthodromic tachycardia induction alone was not considered as a criterium for a high risk form of preexcitation syndrome. The preexcitation syndrome was considered as benign if no tachycardia was induced and a 1 to 1 conduction over accessory pathway (AP) was less than or equal to 240 bpm in control state and less than or equal to 300 bpm after isoproterenol was noted. Follow-up: patients were followed from 3 months to 20 years (mean 6 ± 4 years) by clinical evaluation and ECG recording at the last visit. After 1995, at the end of the electrophysiological study, ablation of accessory pathway was indicated in symptomatic patients or asymptomatic patients after detection of a potentially malignant form of the disease at electrophysiology. All patients in whom AP ablation was performed were seen one month after ablation and then every 1 or 2 years. Antiarrhythmic therapy with beta-blocker and/or flecainide was initiated when the patient refused the AP ablation or in case of failure of ablation. An indication of medical treatment was also used in small children and patients with anteroseptal AP in whom an involution of preexcitation can be expected [13]. Asymptomatic patients in whom there were no criteria of malignancy were not treated.
.2.1.1. Statistical analysis Data are expressed as means ± standard deviation (SD). For categorical variables the chi-squared test was performed. The independent-sample t test procedure was used for continuous variables. The stepwise logistic regression was used to analyse the relationships between presentation with AF (absence/presence = 0/1) as dependent variable and possible predictors (age, gender, accessory pathway location, the shortest cycle conducted through the accessory pathway, inducibility before and after isoproterenol) as independent variables. A p value b 0.05 was considered statistically significant. All statistical analyses were performed by using the SPSS package for Windows (version 17. 0.1, SPSS Inc, Chicago, Illinois).
Table 2 AP location (Septal location = right and left postero septal AP, anterosetal AP: other AP: right AP, Mahaim, undetermined location).
Left lateral Septal Other AP
Total
AF
AVRT
Asymptomatice
Syncope
Adverse presentation
709
44
314
248
94
9
278 (39%) 384 (54%) 47 (7%)
27(61%)*** 15 (34%)** 2 (4.5%)
154 (49%) 142 (45%) 18 (6%)
59 (24%) 166 (67%) 23 (9%)
33 (35%) 57 (61%) 4 (4%)
5 (55.5%) 4 (44.5%)
** p b 0.01, *** p b 0.001: comparison of the group with AF with remaining population.
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Table 3 Electrophysiological data; the left column reports the electrophysiological data (ATD = antidromic tachycardia; CS max HR = maximal heart rate in control state conducted 1 to 1 over AP; iso max HR: maximal heart rate conducted 1 to 1 over AP after isoproterenol, rapid AF: malignant form at electrophysiology, defined above).
AVRT AF ATD CS max HR Iso max HR Rapid AF
Total
AF
AVRT
Asymptomatice
Syncope
Adverse presentation
709
44
314
248
94
9
395 (56%) 153(21.5%) 50 (7%) 193 ± 63 241 ± 68 83 (12%)
25 (57%) 27(61%)*** 5 (11%) 237 ± 69*** 274 ± 78* 17 (39%)***
280 (89%) 54 (17%) 20 (6%) 192 ± 62 247 ± 68 22 (7%)
36 (14.5%) 42 (17%) 16 (6%) 184 ± 60 234 ± 69 22 (9%)
49 (54%) 24 (25.5%) 8 (8.5%) 189 ± 50 242 ± 69 16 (20%)
5 (55.5%) 6 (67%) 1 (12.5%) 283 ± 29 320 ± 29 6 (67%)
*p b 0.05, ** p b 0.01, *** p b 0.0001: comparison of the group with AF with remaining population.
3. Results 3.1. Clinical data of subjects with or without spontaneous AF at the initial presentation (Table 1) We observed the spontaneous occurrence of AF in some patients with conditions associated with increased sympathoadrenal stimulation like stress, emotional stress or surgery (n = 3), hyperthyroidism (n = 2), the postprandial state or the ingestion of alcohol (n = 14). The group of patients with documented spontaneous AF was older than other patients without spontaneous AF with a mean age of 44 ± 16 years versus an average of 34.5 ± 17 years in patients without AF (p 0.00032). The differences were significant with all subgroups, the patients with AVRT (p 0.035), the asymptomatic patients (p 0.02) and the patients with syncope (p 0.01). However the ages of patients with AF varied from 12 to 74 years. Five patients, 2 girls and 3 boys were younger than 18 years and all presented a poorly-tolerated AF with a feeling of dizziness and/or syncope. The percentage of male subjects tended to be higher in the AF group (70%) compared to other patients (59%) (NS 0.2). There was only a significant difference with the subgroup with syncope in which male gender was less frequent than in patients with AF (p 0.03). Regarding the location of the accessory pathway (Table 2), left lateral AP was more frequent than in total population (p 0.003) and septal AP less frequent (p 0.009). However, left lateral AP was as frequent as in patients with spontaneous AVRT, but more frequent than in asymptomatic patients (p b 0.001) or patients with syncope (p 0.003). Septal AP was as frequent as in patients with AVRT but less frequent than in asymptomatic (p 0.001) or patients with syncope (p 0.009). Other locations did not differ. Heart disease was rare in all subgroups and the incidence of associated heart disease did not differ significantly. There is only a trend for a higher incidence of heart disease in patients with AF than in patients with AVRT (p 0.08). 3.2. Data electrophysiological subjects with or without spontaneous AF at the initial presentation (Table 3) AVRT was induced with the same frequency as in total population and in the subgroup with syncope, but less frequently than in patients with spontaneous AVRT (p b 0.0001) and more frequently than in asymptomatic patients (p b 0.0001). The mean age of patients with
spontaneous AF and with inducible AVRT or without inducible AVRT was similar (respectively 43.5 ± 19 and 44 ± 16 years). AF was induced more frequently in patients with spontaneous AF than in total population and in all subgroups (p b 0.0001), except in patients with adverse presentation unrelated to AF. Antidromic tachycardia (ADT) was induced with the same frequency in all subgroups of patients. The maximal heart rate with a 1 to 1 conduction over the accessory pathway was higher in patients with AF than in total population either in control state (p 0.00012) or isoproterenol (p 0.04). When the subgroups are analysed, in control state, the rate was higher in patients with AF than in patients with AVRT (p 0.02) or in asymptomatic patients (p 0.007) and in patients with syncope (p 0.01); after isoproterenol, the rate was higher in patients with AF than in patients with AVRT (0.02) or asymptomatic patients (p 0.09); the differences were not significant in patients with syncope (0.09). However, the maximal heart rate with a 1 to 1 conduction over AP was lower in patients with AF than in patients with adverse presentation unrelated to AF, but the differences did not reach significance because of the small number of the last group (p 0.08) (Table 3). Potentially malignant forms at electrophysiology as defined above were more frequent in patients with AF than in all subgroups except in the subgroup with spontaneous adverse presentation (p b 0.0001). 3.3. Follow-up (3 months to 20 years; mean 6 ±4 years) (Table 4) AP radiofrequency was performed more frequently in patients with AF than in total population (p b 0.0001) and in group with syncope (p b 0.0001) or asymptomatic patients (p b 0.0001). The differences were not significant with patients with AVRT (0.06). The indications of ablation were as frequent as in patients with adverse presentation without AF. Five patients died: one of group with spontaneous AF who had electrophysiological signs of malignancy and who refused all treatments died suddenly; he had stopped all antiarrhythmic drugs and refused the ablation. One patient complaining only of AVRT died suddenly one month after AP ablation. The ablation was successful and without complications. One patient, 21 years old, complaining of recurrent and frequent AVRT's died just before AP ablation. He was studied at the age of 12 years and had signs of malignancy. He had stopped all antiarrhythmic drugs and had accepted the ablation but he died after a new AVRT just before admission. One patient, 70 years old,
Table 4 Follow-up.
Ablation AF
Total
AF
AVRT
Asymptomatice
Syncope
Adverse presentation
709
44
314
248
94
9
321 (45%) 14 (2%)
34 (77%)*** 5 (10%) ***
198 (63%) 5 (1.5%)
43 (17%) 4 (1.6%)
39 (41%) 2 (2%)
7 (78%)
The left column reports the number of patients treated by ablation of the accessory pathway and the number of patients who developed AF during the follow-up. *** p b 0.0001: comparison of the group with AF with remaining population, the group with syncope and asymptomatic group.
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with AVRT died after an important abdominal surgery and the cause of death remained unknown. One asymptomatic patient, 21 years old, died accidentally crushed by a tree. Only 2 of these 5 deaths were directly related to the preexcitation syndrome. Patients with spontaneous AF remained at high risk to have another AF despite AP ablation: recurrences of AF were noted in the group with spontaneous AF in 5 patients, 2 women and 3 men, despite AP ablation in 4 of them. Their age varied from 36 to 74 years (mean age 54 ± 16 years) and was significantly higher than in patients free of AF recurrences (40 ± 17 years) (p 0.028). All these patients had a permanent form of AF. Thirty of 34 (88%) patients of the group with spontaneous AF had no clinical recurrence of AF after ablation without antiarrhythmic drug. Remaining patients were treated by flecainide associated or not with betablockers. Permanent AF developed in 7 patients of the group with only AVRT despite AP ablation in 6 of them; their age varied from 48 to 55 years (mean 52 ± 4); when the 3 deaths are excluded, the frequency of AF is 7/311 (2.2%) that is lower than in the group with spontaneous AF (p b 0.002). One patient of group with syncope developed AF (1%). Among asymptomatic patients, 4 had AF. At the time of the first electrophysiological study, one patient 22 years old had no inducible AF or AVRT and developed a well-tolerated AF at the age of 36 years. Other patients had inducible AF and also a rapid conduction over AP, but they have not been treated. Mean age of these patients at the time of AF was 48.5 ± 18 years. Data of the second electrophysiological study were unchanged. These 4 patients developed a spontaneous AF with adverse presentation, between 3 and 14 years after initial evaluation [15]. AP ablation was performed after the occurrence of AF and the patients had no recurrences after ablation. Multivariate analysis indicated that the maximal rate conducted through the accessory pathway in control state, the induction of AF and age were independent significant predictors of spontaneous AF occurrence (respectively p b 0.0001, b0.0001, b0.01). Other data as gender, accessory pathway location, presence of a heart disease and AVRT induction were not significant. 4. Discussion The incidence of spontaneous documented AF as first event was low (6%) in a population with patent preexcitation syndrome. The risk of AF for asymptomatic patients, patients with spontaneous reentrant tachycardias or those with unexplained syncope was low and less than 2.5%. This incidence is lower than in studies reported more than 20 years ago [1–7]. AF has occurred since the age of 12 years, but the mean age of this population was higher than in remaining subjects. No other clinical finding was associated with AF development. On the other hand, electrophysiological factors of these patients differed from other patients: the AF induction was easy; the induction of AVRT was more frequent than in asymptomatic patients. More, the rate conducted 1 to 1 over AP was more rapid than in other patients. These electrophysiological data explained the higher frequency of malignant forms in this group. Some patients of the present study were recently reported, but clinical data of patients with spontaneous adverse events differed from those of patients presenting with AF [16]. The study of literature related a higher incidence of spontaneous AF from 10% to one third of patients with WPW syndrome [17–20] than in the present study. AF development is not usually associated with heart disease as confirmed in our study. Patients with WPW and obvious spontaneous AF seem to express a predominance of sympathetic activity with vagal inhibition [21,22]. Several hypotheses about initiation of spontaneous AF in patients with AP have been proposed for, such as spontaneous degeneration of an AVRT into AF, the conduction properties of the AP, the effect of the
AP on atrial architecture and the intrinsic atrial vulnerability [23]: the incidence of spontaneous degeneration of AVRT into AF was detected in 16–26% of cases with similar rates in patients with an obvious atrioventricular accessory pathway and those with a concealed AP [4,7]. It has previously been shown that reciprocal tachycardia may increase atrial vulnerability by reducing the length of the atrial cycle length and by increasing the sympathetic tone and atrial stretch due to hemodynamic changes which occurred during AVRT. During electrophysiological study the cycle length of induced AVRT was reported as significantly shorter in patients with AF compared to others, suggesting that more reciprocal tachycardia is rapid, more patient were likely to develop AF. This factor was not studied in our study. A short AP anterograde effective refractory period was found as discriminating in patients with and without spontaneous AF [4,6,7]. The short AP refractory period will be responsible for a rapid ventricular rate during AF associated with poor hemodynamic tolerance and hypoxia which will maintain the atrial arrhythmia. The results of the present study are consistent with the literature because patients with spontaneous AF were found to have a more rapid 1 to 1 conduction over AP than in other patients. During long term follow-up fewer patients will experience spontaneous AF after AP ablation with an incidence rate of recurrence of 6–10% [2,4,20]. However the risk of AF recurrence is higher in patients older than 50 years [24–26]. In the present study, AP ablation was performed in 45% of the patients with a preexcitation syndrome and this treatment is probably the cause of the risk reduction of AF in these patients; only 4 of 248 asymptomatic patients developed AF; 3 of them had inducible rapid AF and now would be systematically treated by AP ablation.
4.1. Study limitations The data associated with increased atrial vulnerability as the shortening of the atrial refractory period and the size of the left atrium on echocardiography are missing. The true incidence of spontaneous AF may be underestimated in our population because we could not take into account the spontaneous episodes of AF which are well-tolerated in patients considered as asymptomatic or the episodes of AF which could have terminated spontaneously before admission in patients with syncope, nor the possible spontaneous AF in patients with known history of reciprocal tachycardia. AF was only documented by ECG. Patient follow-up did not include a systematic Holter monitoring after ablation of the accessory pathway and post-ablation asymptomatic episodes of AF could have been ignored.
5. Conclusions Spontaneous atrial fibrillation in patients with a preexcitation syndrome was uncommon (6%). Patients with spontaneous AF were found to be older in our population, but it can occur in children. The presence of associated heart disease and the location of the accessory pathway were not predictive of atrial fibrillation occurrence. On the other hand, accessory pathway in patients with spontaneous AF had frequently rapid conduction properties and AF was frequently poorlytolerated. Despite of higher risk of AF recurrence than in other patients, 88% of patients who underwent an ablation of accessory pathway had no clinical recurrence of atrial fibrillation. The occurrence of AF in patients initially asymptomatic or presenting with re-entrant tachycardia or syncope was very rare. This lower incidence AF than in previous studies is probably explained by the indication of AP ablation in symptomatic patients and those with inducible supraventricular tachycardia.
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