Advanced interatrial block predicts recurrence of atrial fibrillation after accessory pathway ablation in patients with Wolff‐Parkinson‐White syndrome

Abstract Background Paroxysmal atrial fibrillation (AF) frequently occurs in patients with Wolff‐Parkinson‐White (WPW) syndrome. Although successful ablation of the accessory pathway (AP) eliminates paroxysmal AF in some patients, in other patients it can recur. Hypothesis We investigated the clinical utility of advanced interatrial block (IAB) for predicting the risk of AF recurrence in patients with verified paroxysmal AF and WPW syndrome after successful AP ablation. Methods This retrospective study included 103 patients (70 men, 33 women; mean age, 44 ± 16 years) with WPW syndrome who had paroxysmal AF. A resting 12‐lead electrocardiogram was performed immediately after successful AP ablation to evaluate the presence of advanced IAB, which was defined as a P‐wave duration of >120 ms and biphasic [±] morphology in the inferior leads. Results During the mean follow‐up period of 30.9 ± 20.0 months (range, 2‐71 months), 16 patients (15.5%) developed AF recurrence. Patients with advanced IAB had significantly reduced event‐free survival from AF (P < .001). Cox regression analysis with adjustment for the left atrial diameter and CHA2DS2‐VASc score identified advanced IAB (hazard ratio, 9.18; 95% confidence interval [CI], 2.30‐36.72; P = .002) and age > 50 years (hazard ratio, 12.64; 95% CI, 1.33‐119.75; P = .027) as independent predictors of AF recurrence. Conclusions Advanced IAB was an independent predictor of AF recurrence after successful AP ablation in patients with WPW syndrome.


Paroxysmal atrial fibrillation (AF) occurs frequently in patients with
Wolff-Parkinson-White (WPW) syndrome, with a reported incidence of 9% to 38%. [1][2][3][4] Previous studies have reported a decreased incidence in AF after successful elimination of the accessory pathway (AP), 5,6 indicating that the AP itself may play an important role in the initiation of AF. However, paroxysmal AF still frequently recurs in some patients with WPW syndrome despite successful AP elimination. 3,4,[7][8][9] The identification of patients at high risk for recurrence of AF is of clinical importance because additional therapeutic strategies are needed for these patients.
Interatrial block (IAB) denotes a conduction delay between the right and left atria that manifests in a 12-lead electrocardiogram (ECG) as a P-wave duration of >120 ms. 10,11 A prolonged P-wave with biphasic (±) morphology in the inferior leads represents an even higher degree of IAB and has been referred to as advanced IAB. 10 The appearance of advanced IAB is frequently associated with atrial tachyarrhythmias, and has been found to predict AF in multiple clinical scenarios. [12][13][14][15][16][17][18][19][20] However, the role of advanced IAB in predicting the recurrence of AF after AP ablation in patients with WPW syndrome is unclear. Thus, in the present study, we investigated the clinical utility of advanced IAB for predicting the risk of AF recurrence in patients with verified paroxysmal AF and WPW syndrome after successful AP ablation.

| Electrophysiological study and catheter ablation
The patients underwent an electrophysiological study after all antiarrhythmic drugs had been discontinued for at least five half-lives and before radiofrequency catheter ablation was performed. Three

| ECG analysis
In all patients, a resting 12-lead ECG in sinus rhythm (high-pass filter, 0.05 Hz; low-pass filter, 150 Hz; 25 mm/s; 10 mm/mv) was obtained immediately after the ablation procedure. All ECGs were transmitted electronically using Vhcloud Network Solution (Vales and Hills Biomedical Tech. Ltd., Beijing, China) for storage at the ECG Core Laboratory of Henan Provincial People's Hospital and Fuwai Central China Cardiovascular Hospital. ECGs were manually analyzed on a computer screen using digital calipers with scanning at 300 dots per square inch and 4-fold image amplification. P-waves were measured manually using digital calipers for all 12 ECG leads to identify the longest P-wave duration, as previously described. 13 Advanced IAB was defined as a P-wave of >120 ms accompanied by a biphasic (±) morphology in the inferior leads ( Figure 1). 10 The ECG analysis was performed independently by two observers who were blinded to the patient details, and any differences between the observers were resolved by consensus.

| Patient follow-up
After the ablation procedure, all patients were required to visit their physician at 3, 6, and 12 months and every year thereafter. A 12-lead ECG and 24-hours Holter recording were obtained at every visit. If a patient exhibited any symptoms suggesting tachyarrhythmia, including palpitations, syncope, or dizziness, a new ECG and 24-hours Holter recording were obtained. For any event reported between visit, the patient's medical records were retrieved and reviewed. All patients included in the study were followed up until occurrence of AF or until December 31, 2018 if no AF occurred. AF recurrence was defined as the occurrence of confirmed AF lasting more than 30 seconds as documented by ECG or Holter recordings. 22

| STATISTICAL ANALYSIS
All analyses were performed using statistical software (SPSS version 17.0; SPSS Inc., Chicago, Illinois). Continuous data are presented as mean ± SD and were compared using an unpaired independentsamples t-test or one-way analysis of variance. Categorical variables are presented as a percentage of the group total and were compared using the χ 2 test or Fisher's exact test as appropriate. A Kaplan-Meier estimation with a log-rank test was performed for unadjusted analysis of the association of advanced IAB with the risk of AF recurrence.
Cox proportional hazards regression was used to examine the risk of recurrence. All probability values were two-sided, and values of P < .05 were considered statistically significant.

| RESULTS
In total, 103 patients were enrolled to the study. Advanced IAB was detected in 10 (9.7%) patients. The clinical and electrophysiological characteristics of patients with and without advanced IAB are shown in

| DISCUSSION
The main findings of the present study are that advanced IAB and age > 50 years were independent predictors of AF recurrence after successful AP ablation in patients with WPW syndrome.
Previous studies have shown that patients with WPW syndrome have a high incidence of paroxysmal AF. [1][2][3][4] Recent studies suggest that although AP ablation alone may prevent further AF recurrence in the majority of these patients, the incidence of paroxysmal AF remains higher than that in the general population even after successful AP ablation. 3,4,[7][8][9] This is supported by our finding that 15.5% (16/103) of patients with verified paroxysmal AF and WPW syndrome developed AF recurrence after successful AP ablation. This phenomenon may be explained by the two mechanisms of paroxysmal AF in F I G U R E 1 A, P-wave morphology in a representative patient with Wolff-Parkinson-White syndrome in the inferior leads before accessory pathway (AP) ablation. B, Typical P-wave morphology of advanced interatrial block with P-wave duration >120 ms and biphasic (±) morphology in the inferior leads in the same patient after AP ablation patients with WPW syndrome reported in previous studies. 9,23,24 One mechanism involves AP-dependent atrial electrophysiological abnormalities that are reversible, and the other involves AP-independent atrial electrophysiological abnormalities that are intrinsic and seemingly irreversible even after successful AP ablation.
Previous studies have examined several predictors of AF recurrence in patients with WPW syndrome after AP ablation. Kawabata et al. 6 investigated the relationship between the B-type natriuretic peptide (BNP) level and AF recurrence after AP ablation in patients with WPW syndrome and found that a BNP level ≥ 40 pg/mL was an independent predictive factor for AF recurrence. However, the BNP level might fluctuate because it is affected by many factors. In a study by Hiraki et al., 25 a filtered P-wave duration of >130 ms on signalaveraged electrocardiography was an independent predictor of recurrence of AF after AP ablation. In addition, Aytemir et al. 26 evaluated the predictive value of the maximum P-wave duration and P-wave dispersion on a 12-lead surface ECG in predicting AF recurrence, and their multivariate analysis showed that only a P-wave dispersion of ≥32.5 ms was an independent predictor of AF recurrence. In the present study, we evaluated the role of advanced IAB (ie, P-wave duration of >120 ms accompanied by a biphasic (±) morphology in the inferior leads on 12-lead surface ECG) in predicting the risk of AF recurrence in patients with WPW syndrome after AP ablation. The univariate and multivariate analyses showed that advanced IAB was associated with AF recurrence. Two potential mechanisms may account for these findings. First, advanced IAB is likely a presentation of AP-independent atrial electrophysiological abnormalities that remain after successful AP ablation. In support of this, advanced IAB was previously reported to reflect the underlying atrial substrate with atrial fibrosis 27,28 and to be associated with the development of AF. [12][13][14][15][16][17][18][19][20] Second, advanced IAB may play a role in initiating and maintaining reentry circuits by promoting the occurrence of unidirectional block, 29 an important mechanism in the development of

CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.