Defibrillation threshold of internal cardioversion prior to ablation predicts atrial fibrillation recurrence

Abstract Background Many studies have reported the predictors of atrial fibrillation (AF) recurrence after persistent AF (peAF) ablation. However, the correlation between the atrial defibrillation threshold (DFT) for internal cardioversion (IC) and AF recurrence rate is unknown. Here we investigated the relationship between the DFT prior to catheter ablation for peAF and AF recurrence. Hypothesis DFT prior to ablation was the predictive factor for AF recurrence after peAF ablation. Methods From June 2016 to May 2019, we enrolled 82 consecutive patients (mean age, 65.0 ± 12.4 years), including 45 with peAF and 37 with long‐standing peAF, at Hamamatsu Medical Center. To assess the DFT, we performed IC with gradually increasing energy prior to radiofrequency application. Results Forty‐nine and 33 patients showed DFT values less than or equal to 10 J (group A) and greater than 10 J or unsuccessful defibrillation (group B). During the mean follow‐up duration of 20.5 ± 13.1 months, patients in group B showed significantly higher AF recurrence rates than those in group A after the ablation procedure (p = .017). Multivariate analysis revealed that DFT was the only predictive factor for AF recurrence (odds ratio, 1.07; 95% CI, 1.00–1.13, p = .047). Conclusions The DFT for IC was among the strongest prognostic factors in the peAF ablation procedure.

duration, left atrial low voltage area, and increased brain natriuretic peptide (BNP) levels contribute to AF recurrence after catheter ablation. [9][10][11][12][13] Atrial defibrillation threshold (DFT) is correlated with AF duration. [14][15][16][17] Giuseppo B, et al. indicated that AF duration was a predictor of an increased DFT. Moreover, some studies demonstrated the relationship between the effects of external cardioversion (EC) and catheter ablation. 17 A high-energy shock is required for direct-current EC in peAF; however, internal cardioversion (IC) uses a relatively lowenergy shock but can also be useful for defibrillation. A newly developed IC system with a lower-energy shock is readily applicable in defibrillation during catheter ablation. This system can eliminate the effects of physique and pulmonary parenchyma on defibrillation, making it possible to precisely estimate a link between AF substrate and DFT. Some studies have demonstrated an association between the DFT for IC and AF recurrence following catheter ablation. [18][19][20] However, the study designs have different approaches from our study.
In this report, we estimated the DFT for IC prior to catheter ablation for peAF as well as the effects of catheter ablation. Moreover, we investigated whether a high DFT for IC could predict AF recurrence after catheter ablation. Catheter and Surgical AF Ablation. PeAF and long-standing peAF were defined as AF lasting for more than a week and more than a year without resolution, respectively. We excluded patients with prior AF ablation, prior maze procedure, abnormal thyroid function, prior heart valve surgery, ongoing dialysis, or abnormal liver function, and who were lost to follow-up.
All antiarrhythmic drugs were discontinued at least 1 week prior to the catheter ablation. After the catheter ablation, the medication was continued or discontinued based on the operator's discretion.
The medication was occasionally discontinued due to the absence of AF recurrence. All patients were treated with warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban for at least 4 weeks prior to the catheter ablation. The anticoagulant therapy was stopped the morning of the day of the procedure. Intraprocedural anticoagulation for catheter ablation was achieved with heparin at doses that maintained the activated clotting time at >250-300 s. General anesthesia was maintained with propofol.
All patients provided written informed consent before the procedure. The study was conducted in accordance with the Declaration of Helsinki and approved by the hospital's ethics committee.

| Internal cardioversion
At the start of the procedure, a Bee AT catheter (Japan Lifeline Co Ltd, Tokyo, Japan) was advanced into the distal coronary sinus (CS) through the right subclavian vein. The distal and middle eight poles were positioned in the distal CS and right atrial lateral wall, respectively. The IC was performed using the Bee AT catheter and a SHOCK AT (Japan Lifeline Co. Ltd., Tokyo, Japan) just before beginning the radiofrequency (RF) application with gradually increasing energy to assess the DFT. The initial IC energy was set to 5 J; thereafter, it was increased according to the following protocol until successful defibrillation was achieved: 5, 10, 15, 20, and 30 J. Patients were divided into two groups based their respective DFT values. We used 10 J as a cut-off value according to the previous report by Jung W et al. 21 Patients with DFT values less than or equal to 10 J and greater than 10 J or in whom defibrillation was unsuccessful were divided into groups A and B, respectively.

| Follow-up
After the catheter ablation, the patients visited our hospital on a monthly basis, during which they underwent an ECG examination, a Holter monitor test (if applicable), or an event recorder check to explore symptoms suggestive of AF recurrence. If these symptoms were found, the patient was instructed to visit our hospital immediately. AF recurrence was defined as a symptomatic and/or documented AF episode lasting more than 30 s.

| Statistical analysis
Continuous data are shown as mean ± SD or median and quartile. A   Figure 1 shows the distribution of the DFT for IC as a bar graph. There were no significant intergroup differences in age, body weight, left atrial dimension, ejection fraction, or laboratory findings ( Table 1). The ratio of the long-standing peAF was significantly higher in group B than in group A. In terms of the catheter ablation strategy, a higher ratio of patients in group B underwent box isolation. There was no significant intergroup difference in in the efficacy of antiarrhythmic drug therapy.

| Complications
A patient in group B developed pericardial tamponade, which resolved after pericardial drainage. Barring the aforementioned complication, no other major complications such as symptomatic PV stenosis, cerebral embolism, phrenic nerve palsy, or atrioesophageal fistula were noted.

| Patient characteristics of AF recurrence versus AF non-recurrence group
The ratios of the long-standing peAF and DFT were significantly higher in the AF recurrence than that of the AF non-recurrence group ( F I G U R E 2 Kaplan-Meier curve analysis of the incidence of atrial fibrillation recurrence after the ablation procedure. Group A: equal or lower than 10 J (5 J, 10 J). Group B: higher than 10 J or unsuccessful defibrillation (15 J, 20 J, 30 J, or unsuccessful defibrillation) Our study showed that a high DFT for IC before RF ablation predisposed patients to a poor prognosis of AF after catheter ablation.

| Predictors of AF recurrence
The box isolation rate was significantly higher in group B than in group A patients. Box isolation might have been performed in many intractable cases; however, no significant intergroup differences were observed in the ablation strategy. Complete PVI was achieved in both of our study groups. Moreover, it is assumed that the ablation strategy did not affect AF recurrence in either of our study groups. In group B, with a high DFT, the percentage of patients with longstanding peAF was significantly higher than that in group A, which probably influenced AF prognosis after ablation.
Our study demonstrated that a high DFT was the strongest prognostic factor for AF recurrence after the ablation procedure. Therefore, we speculate that a high DFT is correlated with atrial remodeling, due to which the success rate of catheter ablation in AF is gradually decreasing. The concept of the left atrial low-voltage areas is a well-established marker for atrial remodeling and AF recurrence after PVI. 12 The presence of left atrial low-voltage areas may correlate with the high DFT; however, this was not investigated in this study.
In recent reports, in addition to PV isolation, additional ablation targeting the left atrial substrate using linear ablation, 23 CFAE ablation, 24 CARTOFINDER, 25 and ExTRa mapping 26 is reportedly effective for improving the prognosis of peAF ablation. To improve the performance after peAF ablation in patients with a high DFT, these methods may reduce recurrence after AF ablation.

| LIMITATION
This study has some limitations that should be noted. First, catheter position may be correlated with the DFT. However, in some cases, the Bee AT catheter could not be positioned properly due to right atrial enlargement, which possibly affected the DFT. As such, there may be problems with the reproducibility of the DFT. Second, we found no correlation between the LA diameter and AF recurrence.
Only patients who underwent ablation were included; thus, selection bias may have occurred at the indicated stage, resulting in no correlation between the LA diameter and AF recurrence. Hence, a randomized study with a larger study population is needed to clarify the relationship between the DFT and AF prognosis after catheter ablation.

| CONCLUSION
In patients with peAF undergoing IC with a high DFT, the AF recurrence rate was higher even with additional RF applications after PVI (such as box isolation). Moreover, DFT for IC is among the strongest predictors for AF recurrence.

DATA AVAILABILITY STATEMENT
Data of this research are not shared.