Effectiveness and safety of single transseptal ablation for atrial fibrillation in real‐word practice

Abstract Background We have previously reported that unilateral groin‐single transseptal (ST) ablation in patients with paroxysmal atrial fibrillation (AF) was safe and significantly reduced patient discomfort compared with bilateral groin‐double transseptal (DT) ablation. Hypothesis In the present study, we hypothesized that ST ablation would be as effective and safe as DT ablation in real‐world practice like previous study. Among the 1765 consecutive patients in the Yonsei AF ablation cohort from October 2015 to January 2020, 1144 patients who underwent radiofrequency ablation were included for the analysis. Among them, 450 underwent ST ablation and 694 underwent DT ablation. Results The total procedure time, ablation time, and fluoroscopy time were longer in the ST group than in the DT group (p < .05 for all). The hospital stay after catheter ablation was 1.3 ± 1.1 days which was longer in DT group than ST group (p = .001). No significant difference was observed in the complication rate (p = .263) and AF‐free survival rate (log‐rank p = .19) between the groups. However, after excluding patients who used antiarrhythmic drugs when AF recurred, the AF‐free survival rates were lower in the DT group than in the ST group before and after propensity score matching (log‐rank p = .026 and .047, respectively). Conclusion Although the ST approach increases the procedure time compared with the DT approach owing to the need for more frequent catheter exchanges, the ST approach is a feasible and safe strategy for AF ablation in terms of rhythm outcomes and risk of complications.


| INTRODUCTION
Catheter ablation is effective in rhythm control of atrial fibrillation (AF) and maintaining sinus rhythm. [1][2][3][4][5] After a study identified triggers of paroxysmal AF in the pulmonary veins (PVs), catheter ablation of AF has become a more common treatment method. 6,7 Complete PV isolation is a well-proven endpoint for catheter ablation by encircling the PVs. 8,9 To approach the PVs via the left atrium (LA) during AF ablation, transseptal puncture is performed. 10 Although some complications have been reported, such as cardiac tamponade, stroke, and persistence of the septal defect after transseptal puncture, [11][12][13] several reports have shown the safety of transseptal puncture. 14,15 During PV isolation, most operators use the double transseptal (DT) approach for simultaneous PV potential monitoring and ablation.
We have previously compared unilateral groin (UG) puncturesingle transseptal (ST) ablation with the conventional bilateral groin (BG) puncture-double transseptal (DT) ablation in a prospective randomized trial. 16 No differences in clinical outcome and complications were found between the two groups. However, patient's discomfort about hemostasis was reduced in the UG-ST group than the BG-DT group. The number of patients in our previous prospective study was relatively small. Therefore, in the present study, we sought to assess the effectiveness and safety of ST ablation compared to those of DT ablation in patients with AF in real-world clinical practice.

| Study population
The study protocol adhered to the Declaration of Helsinki and was approved by the Institutional Review Board of Yonsei University Health System. All patients provided written informed consent for inclusion in the Yonsei AF Ablation Cohort Database (registered at clinicaltrials.gov as NCT02138695). Among the 1765 consecutive patients in the Yonsei AF ablation cohort from October 2015 to January 2020, those who underwent de novo radiofrequency catheter ablation for circumferential PV isolation (CPVI) were included in the current analysis ( Figure 1). The exclusion criteria were as follows: (1) valvular AF, (2)

| Postablation follow-up
Patients without antiarrhythmic medications were discharged after the procedure unless early recurrence of AF/atrial tachycardia (AT) or symptomatic frequent atrial premature beats were evident. The patients regularly visited the outpatient clinic at 1, 3, 6, and 12 months after catheter ablation and every 6 months thereafter or whenever symptoms occurred. All patients underwent electrocardiography (ECG) at each visit and 24 h Holter recordings at 3 and 6 months after catheter ablation and every 6 months thereafter according to the guideline. 18 Holter monitoring or event monitor recordings were obtained when the patients reported symptoms of palpitation suggestive of arrhythmia recurrence. AF recurrence was defined as any episode of AF or AT lasting for at least 30 s. Any ECG documentation of an AF recurrence within a 3-month blanking period was diagnosed as an early recurrence, and an AF recurrence >3 months after the procedure was diagnosed as a clinical recurrence.

| Statistical analysis
For the comparison of baseline variables, continuous variables were analyzed using Student's ttest or analysis of variance, as appropriate.
Categorical variables were analyzed using Pearson's chi-square test.

| Clinical rhythm outcomes
The mean follow-up duration was 17.8 ± 13.8 months ( The AF recurrence-free survival rate was not significantly different between the ST group and the DT group in the Kaplan-Meier analysis (log-rank p = .190, Figure 2(A)). However, after excluding patients who used AADs when AF recurred, the AF recurrence free-survival rate was lower in the DT group than in the ST group (log-rank p = .026, Figure 2(B)).
Among patients who recurred AF, 77 patients performed redo-ablation. (Table 3). A total of eight patients (10.4%) observed 4PV isolation when PV potential was checked in redo-RFCA. There was no significant difference in PV reconnection between ST group and DT group.

| Outcomes after propensity score matching
After propensity score matching to balance the baseline characteristics between the two groups, the procedure time, ablation time, and fluoroscopy time were still significantly longer in the ST group than in the DT group ( showed no significant difference between the two groups after propensity score matching (log-rank p = .600, Figure 2(C)). The AF-free survival rate was also lower in the DT group than in the ST group after excluding patients with AAD use in propensity matching (log-rank p = .047, Figure 2(D)).

| Major findings
Our study divided patients undergoing AF ablation based on the approach used (ST and DT) to determine the feasibility and safety of the ST approach. Although the procedure time was increased in the ST group, the incidence of complications was not significantly different between the ST and DT groups. The AF-free survival rates in the Kaplan-Meier curve were not significantly different between the two groups. After excluding patients who used AADs when AF recurred, the AF-free survival rates without AAD use were lower in the DT group than in the ST group before and after propensity score matching. Hospital stay after RFCA was significantly reduced in ST group compared to DT group. Reducing patient's discomfort during hemostasis might be helpful to reduce hospital stay after RFCA.

| Potential complications of the ST approach
In the ST approach, the risk of stroke might increase because catheters are exchanged several times during the procedure. Therefore, we always irrigated the sheath with saline before catheter exchange to remove clots and air. However, in the current analysis, no cases of stroke occurred in the ST group and three cases of stroke occurred in the DT group. In the DT group, the operator could monitor the PV signals simultaneously during ablation. Therefore, a concern regarding an increased risk of AF recurrence may exist in the ST group because of the higher possibility of missing the gap along the PV antral lesions.
However, our results showed no difference in the rate of AF recurrence between the two groups. Also, our results showed no difference in the number of PV reconnection when we performed redo-RFCA.
Additionally, the rates of AF recurrence were slightly lower in the ST group than in the DT group after excluding patients using AADs.
However, it is difficult to conclude that the ST approach is more effective than the DT approach in the current setting, and further studies would be needed to clarify this issue.

| Limitations
Our study has several limitations. First, this was an observational study using a single-center prospective registry that included a highly selected group of patients referred for AF catheter ablation. The choice of the ablation strategy depended on the operators' discretion and experience. Also, selecting the ST or DT approach was decided by operator preference and it could result in selection bias. To compensate for this limitation, we performed propensity score matching to adjust the baseline clinical characteristics of the two groups. Second, there was a significant difference in the percentage of AAD use between the two groups. Physicians tend to prescribe AADs to patients who are more likely to develop AF recurrence, such as patients with more premature atrial contractions. Therefore, this could have affected the AF-free survival rate after the catheter ablation.
Third, since our study was not randomized, the operator variable could affect the procedure and the outcome of the study. Fourth, unlike our previous report, the present study had no objective indicator to prove the reduction of discomfort because of the retrospective design.

| CONCLUSION
The ST approach is as safe as the DT approach and has the advantage of reducing patient discomfort with respect to hemostasis. Although the ST approach increases the procedure time compared to the DT approach owing to the need for more frequent catheter exchanges, the ST approach is a feasible and safe strategy for AF ablation in terms of rhythm outcomes and risk of complications.