Prognostic Value of Inferior Shift of P wave Axis after Catheter Ablation for Longstanding Persistent Atrial Fibrillation based on Dallas Lesion Set Including Anterior Line

Background and Objectives: Although an anterior linear ablation is an effective lesion set in radiofrequency catheter ablation (RFCA) for longstanding persistent atrial fibrillation (L-PeAF), its durability for bidirectional block (BDB) is only about 60% at repeat procedure. We hypothesized that changes in electrocardiogram (ECG) may predict an anterior line block state and the clinical outcome of L-PeAF ablation. Subjects and Methods: We studied 304 L-PeAF patients (77% male, 60±10yrs), who consistently underwent RFCA Dallas lesion set (circumferential pulmonary vein isolation, posterior box lesion, and anterior line) protocol with subsequent comparison of pre-procedural and post-procedural P wave axes, and one year follow-up (n=205) sinus rhythm (SR) ECGs. Results: 1. P wave axis shifted inferiorly at immediate post-procedure (p<0.001), and was independently correlated with BDB of anterior line (ß=10.4, 95% confidence interval [CI] 2.79-17.94, p=0.008). 2. The degree of post-procedural inferior shift of P wave axis did not reflect clinical recurrence within one-year (n=205, p=0.923), potentially due to conduction recovery of an anterior line. However, among 160 patients without clinical recurrence within one-year, P wave axis at one-year ECG was independently associated with very late recurrence of AF after one-year (n=160, hazard ratio [HR] 0.98; 95% CI 0.97–0.99, p=0.001), during 45.6±16.7 months of follow-up. 3. Among 22 patients who underwent repeat procedures, P wave axis shift was more significant in patients with maintained BDB of an anterior line than in those without (p=0.015). Conclusion: An inferior shift of P wave axis reflects the achievement and the maintenance of an anterior line BDB, and is associated with better long-term clinical outcome after catheter ablation for L-PeAF based on Dallas lesion set.


Introduction
Radiofrequency catheter ablation (RFCA) has become an accepted standard rhythm control treatment option in antiarrhythmic drug (AAD) resistant atrial fibrillation (AF) management. 1 Persistent AF (PeAF) accompanies significant arrhythmic substrates and a higher AF burden. Current technology, however, such as an irrigated tip ablation catheters or three-dimensional electroanatomical mapping systems, have improved rhythm control outcomes remarkably. A PeAF catheter ablation, in terms of reducing the AF burden, is more effective than AAD. 2 We previously reported that an anterior linear ablation is an effective strategy in RFCA for PeAF, 3 mimicking the Dallas lesion set of surgical mini-maze procedure. 4 However, catheter ablation for longstanding PeAF (L-PeAF) remains a challenge, owing to the long-term recurrence of AF 5 and limited long-term clinical outcomes of linear ablation.
Furthermore, L-PeAF is vulnerable to AF progression, 6 even following successful catheter ablation. An AF recurrence prediction, therefore, employing simple non-invasive techniques, remains an unresolved clinical need in patients undergoing AF ablation. P wave analysis using standard surface 12-lead electrocardiography (ECG) is a simple and cost-effective modality for determining the prognosis of AF. We recently reported that low P wave amplitude in lead I with displaced interatrial conduction, 7 and prolonged PR interval, 8 are associated with a higher clinical recurrence rate of AF after catheter ablation.
However, the clinical value of ECG in the context of ablation for AF is not well-established thus far, and the study populations in most studies included patients with paroxysmal AF (PAF). 7,9 Therefore, we hypothesized that there would be a change in P wave morphology on ECG in association with linear ablation after catheter ablation in L-PeAF patients, and that those changes would have clinical implications. The purpose of this study was to determine long-term P wave changes after RFCA, their relationship with bidirectional block (BDB) of the linear ablation, and their prediction power for very late recurrence of AF in patients with L-PeAF.

Measurement of electrocardiography parameters
A mean duration for ECG documented AF was 60.3±99.7 months. Standard 12-lead ECGs (GE Healthcare, Marquette, MAC5500, Waukesha, WI, USA) were acquired after restoring sinus rhythm by electrical cardioversion (2.47±3.08 months before catheter ablation), immediately after catheter ablation, and at one year after the procedure. The sweep speed was 25 mm/s and the device was calibrated to 1 mV/cm. The heart rate, PR interval, and P-axis were automatically calculated with the available equipment. All P wave measurements were conducted by a single technician who was blinded to the clinical data. The correlation coefficient for the intra-class correlation was 0.96.

Radiofrequency catheter ablation
Details regarding electrophysiological mapping, RFCA technique and strategy have been described in previous studies. 10  BDB was confirmed by differential pacing maneuvers and activation mapping in all patients. 11 Additional ablations were performed to generate BDBs of these lines in cases in which BDBs of linear ablation lines were not achieved. However, ablation lines were kept unblocked to avoid collateral damage were not able to achieve linear ablation BDBs after three attempts. If there were mappable AF triggers or atrial premature beats (APCs) with isoproterenol infusion (5 μg/min), we carefully mapped and ablated those non-PV foci as much as possible.
All RFCA procedures were conducted by two operators with more than 10 years of experience, in strict accordance to the aforementioned protocol.

Follow-up after ablation
All patients were monitored with continuous ECG overnight and discharged the day after the procedure. Of the total number of patient, 24.6% were discharged with AADs due to high chance of AF recurrence. AADs were discontinued if there was no evidence of AF/AT recurrence after the third month Holter. All patients were followed up with at the outpatient clinic at one, three, six, and 12 months, and every six months thereafter or whenever symptoms occurred after the ablation. Rhythm follow-ups every visit by ECG Consensus Statement guidelines. 12 In addition, Holter monitoring or event recording was used in an attempt to diagnose arrhythmia, if the patient presented with palpitations. We defined recurrence of AF as any episode of AF or atrial tachycardia lasting longer than 30 seconds. 12 Any ECG documentation of AF recurrence after three months was diagnosed as clinical recurrence. An episode of recurrent AF occurring more than a year after ablation was defined as a very late recurrence.
In AF/atrial tachycardia recurrence patients, rhythm control was managed by AADs with or without cardioversion. It was our practice to recommend a second ablation procedure to these patients, unless sinus rhythm was maintained with AADs.

Statistical analysis
Continuous variables were reported as mean ± standard deviation and analyzed using independent t-tests or the Mann-Whitney U test. The normality was determined using the Kolmogorov-Smirnov A p-value ≤0.05 was considered statistically significant.  Figure 2A).

P wave axis shift and AF recurrence after catheter ablation for persistent AF
Among the 205 patients who had one-year follow-up SR ECG,    Figure   2D), and Kaplan-Meier analysis showed a significantly higher very late clinical recurrence of AF in patients with ΔP-axis < 6° (Log rank p=0.004 in overall, p=0.022 without AAD; Figures 2E and 2F).

P wave axis predicts bidirectional block state of anterior line in repeat ablation
During the follow-up periods, 39 patients underwent a repeat procedure at 16.8±10.8 months, after de novo procedure. Among

Discussion
In this study, we evaluated the clinical and prognostic implications of P wave axis by comparing sinus rhythm ECGs before and after ablation for L-PeAF with consistent ablation lesion set, including posterior box lesion and anterior linear ablation. An anterior line BDB was independently associated with inferior shifting of the P wave axis, and maintaining an inferiorly shifted P wave axis was associated with significantly low very late recurrence rate of AF one year after the procedure.
Activation map after de novo procedure One-year post-ablation P-axis : 83°P re-ablation P-axis : 57°O ne-year post-ablation P-axis : 75°O ne-day post-ablation P-axis : 72°P re-ablation P-axis : 48°O ne-day post-ablation P-axis : 73°O ne-year post-ablation P-axis : 51°P re-ablation P-axis : 53°O  Figure 3. Examples of changes in P wave axis before, one day after and one year after AF ablation, including anterior line and posterior box lesion. All three patients underwent successful bi-directional blocks of an anterior line during a de novo procedure. Patient A. This patient did not recur AF for 20 months after ablation. Patient B. This patient recurred AF, but anterior line block was maintained at redo procedure, conducted at 17 months after the de novo procedure. Patient C. A previously blocked anterior line was re-connected at the redo-procedure, conducted at 14 months after the de novo ablation. AF, atrial fibrillation

Changes of P wave axis after ablation
The morphology of the P wave observed using surface ECG represents both atrial electrical activation and possible changes in some pathological conditions. 13 AF catheter ablation may result in altered impulse conduction in the atrium, and after linear ablation, especially. Previous studies comparing post-AF ablation ECG have reported changes in P wave duration, but those were mostly limited to PAF population or CPVI without linear ablation. 14,15 In the current study, we focused on changes in P wave axis among ECG parameters, since a consistent linear ablation lesion set was performed in L-PeAF patients. Patients with L-PeAF could have an extraordinary amount of left atrial scar.
These intrinsic left atrial scars can affect atrial conduction.
However, use of the Dallas lesion set, which includes a posterior box lesion and anterior line, resulted in an inferior shift of the P wave axis. Especially, it was mainly related to the completeness of an anterior line in this study. An anterior line crosses the septopulmonary, septoatrial, and Bachmann's bundles, 16 injuring these muscle fibers and changing interatrial conduction. 17,18 An anterior linear ablation therefore results in significant changes in the LA activation pattern, mainly through septal activation and the crista terminalis. 18,19 This shifts the sum of the atrial conduction vector more towards the inferior axis. 20

Prognostic value of the P wave axis
Recent studies suggest a prognostic value of the morphology of the P wave in terms of the clinical outcome after AF ablation. This prognostic value is mostly related to a pre-existent prolonged P wave duration and a reduced P wave amplitude, 7,15 or less shortening of the post-procedural P wave duration. 14 In this study, we found that the P wave axis change has a prognostic value after catheter ablation for L-PeAF, including anterior linear ablation.
We postulated that there was a dependence of a prognostic value of the P wave axis inferior displacement on a degree of an anterior linear ablation completed. Pak et al. 3  it is encouraging to discover a sheer possibility of a simple noninvasive ECG parameter's (i.e., P wave axis) role in estimating the maintenance of a conduction block or in approximating a longterm risk of very late clinical recurrence in L-PeAF patients who underwent catheter ablation, including an anterior line ablation.
Further research involving multi-center studies on ECG analysis in a higher number of patients with L-PeAF is warranted.

Limitations
This was a single-center cohort study that included a selective group of patients referred for L-PeAF catheter ablation; therefore, its results cannot be generalized. A high percentage of patients had L-PeAF in our cohort. It was possible to have included some paroxysmal or persistent AF patients who only underwent ECGs when they were in atrial fibrillation, and who were actually in sinus rhythm most of the time between the ECGs. We included only those patients with L-PeAF who underwent RFCA with the same lesion set, including anterior line. However, few patients showed AF trigger or APC frequently on isoproterenol infusion after standard lesion set ablation, focus was searched and ablated.
This might make the lesion set heterogeneous, but its effect on conduction was probably minimal as compared with linear ablation, since focal ablation was performed. Although we derived the importance of anterior line based on multivariate regression analyses, we cannot exclude the potential inter-dependence between anterior line and other linear lesions. In this study, we included the patients taking AAD in analyzing the role of P wave axis in predicting very late clinical recurrence of AF one year after catheter ablation. However, the result found was consistent with that among patients without AAD.

Conclusions
An inferior shift of P wave axis reflects the achievement and maintenance of an anterior line BDB, and tends to have a correlation with better long-term clinical outcomes following catheter ablation for L-PeAF.