Bachmann's Bundle Modification in Addition to Circumferential Pulmonary Vein Isolation for Atrial Fibrillation: A Novel Ablation Strategy

Background Bachmann's bundle (BB) is the main pathway of interatrial connection that could be involved in the development of atrial fibrillation (AF). Based on this hypothesis, we raised a novel ablation strategy, BB modification in addition to circumferential pulmonary vein isolation (CPVI-BB) in patients with AF. Methods A retrospective cohort of patients with AF who underwent CPVI-BB or CPVI alone from March 2018 to July 2021 was enrolled in our study. Propensity score matching was performed in patients with paroxysmal AF and persistent AF, respectively, to reduce the risk of selection bias between the treatment strategies (CPVI-BB or CPVI alone). The primary endpoint was overall freedom from atrial arrhythmia recurrence through 12 months of follow-up. Results Our propensity score-matched cohort included 82 patients with paroxysmal AF (CPVI group: n = 41; CPVI-BB group: n = 41) and 168 patients with persistent AF (CPVI group: n = 84; CPVI-BB group: n = 84). Among patients with persistent AF, one-year freedom from atrial arrhythmia recurrence rate was 83.3% in the CPVI-BB group and 70.2% in the CPVI group (log-rank P = 0.047). Among patients with paroxysmal AF, no significant difference was found in the primary endpoint between two groups (85.4% in the CPVI-BB group vs. 80.5% in the CPVI group; log-rank P = 0.581). In addition, procedure-related complications and recurrence of atrial tachycardia or atrial flutter were similar between the two treatment groups, regardless of the type of AF. Conclusions BB modification in addition to CPVI is an effective approach in increasing the maintenance of sinus rhythm in patients with persistent AF, while it does not improve the clinical outcomes of radiofrequency catheter ablation in patients with paroxysmal AF.


Introduction
Catheter ablation is a well-established treatment for patients with symptomatic atrial fbrillation (AF) [1,2].Circumferential pulmonary vein isolation (CPVI) is identifed as the cornerstone for ablation procedures due to the prominent role of the pulmonary vein (PV) in the initiation of AF [1,2].However, long-term outcomes of CPVI alone sometimes seem less satisfying, and additional linear ablation lesions have been investigated in paroxysmal and persistent AF in an attempt to improve ablation efectiveness [3][4][5][6].
Bachmann's bundle (BB) is a muscular structure connecting the right and left atrial walls, representing the main pathway of interatrial conduction.Recent trials have demonstrated the role of BB as a critical determinant of AF, and BB may be involved in the pathogenesis and perpetuation of a number of unstable reentry circuits [7][8][9].Results of trials targeting the BB have been published, and in these trials, BB ablation through an epicardial approach and ablation in the region of BB insertion through an endocardial approach were efective in restoring sinus rhythm [5,6,10].Terefore, we hypothesized that CPVI plus BB modifcation through an endocardial approach could improve clinical outcomes in AF.

Patient Population and Study Design.
A total of 482 consecutive patients undergoing their frst radiofrequency (RF) ablation for AF from March 2018 to July 2021 were screened.Patients were excluded if (1) there was additional ablation besides CPVI and BB modifcation in the left atrium for an identifed non-PV focus and/or poor atrial substrate; (2) AF with valvular disease; and (3) LA diameter ≥50 mm (Figure 1).Te duration of persistent AF was assessed based on the documentation of AF on an electrocardiogram (ECG) or 24-h Holter ECG monitoring.In our institution, CPVI plus BB modifcation emerged as an alternative ablation method to CPVI and the decision to use BB modifcation was made the day before procedure to avoid selection bias during the procedure.Clinical data were extracted from the hospital's electronic health recording system, and propensity score models were constructed in patients with paroxysmal AF and persistent AF, respectively, to minimize selection bias in the baseline between the CPVI group and CPVI-BB group.Te study protocol was carried out under the ethics principles established by the Declaration of Helsinki and approved by the local ethics committee.All patients provided written informed consent for the ablation procedure and enrollment in our study.

Common Pathways of the Procedure.
In general, transesophageal echocardiography was routinely performed before procedures to evaluate the presence of thrombi.Antiarrhythmic drugs were stopped for at least 5 half-lives, and a single dose of a novel oral anticoagulant was skipped just before the procedure.An electrophysiological study and ablation procedure would be performed under conscious sedation with fentanyl.Briefy, two right femoral accesses (8.5-F sheaths) were used to perform transseptal puncture.Heparin was administered to maintain an activated clotting time of 300-350 seconds(s) during the procedure after transseptal puncture.A decapolar catheter was advanced to the coronary sinus through left femoral or right jugular access.A 20-mm decapolar circular or fexible mapping catheter was used to map the left atrium (Lasso or PentaRay; Biosense-webster, USA), and a 3.5-mm open irrigated-tip ablation catheter was used to deliver RF energy for the ablation.Before ablation, a detailed image reconstruction of the left atrium and PV was obtained, and the total area of the left atrium and area of the scar (voltage amplitudes of <0.15 mV) were calculated.RF energy was delivered at 35-40 W with a contact force of 5-15 g and an impedance of 120-140 ohms.Te ablation index (AI), a lesion quality marker, was targeted at 360 to 380 for the posterior wall and 400 to 420 for the anterior wall and BB modifcation.

PVI and BB Modifcation
Procedure.After the left atrial geometry was reconstructed, the right PV antrum was ablated frst, followed by the left PV antrum in both groups.RF was applied 0.5-1.5 cm proximal to the ipsilateral PV ostia in a wide-area circumferential pattern.Te Lasso or PentaRay catheter was placed in all 4 PVs to confrm PVI, and additional ablation would be performed if PVI was not complete.Isoproterenol was infused intravenously to elicit any nonpulmonary vein triggers.Persistent PVI was confrmed 30 minutes after the initial documentation of PVI.For patients in the CPVI-BB group, additional anterior linear ablation which originated from the roof of the right superior PV toward the mitral annulus (12 o'clock direction in left anterior oblique view) but was discontinued at the level of the inferior base of the left atrial appendage (LAA) was performed after CPVI.Diferent from conventional anterior wall linear ablation which connects the mitral annulus with the right superior PV [11], our ablation lesion is relatively short, just across the region of Bachmann's bundle (Figure 2).Te endpoint of BB modifcation was the formation of consecutive scars without gaps in the linear ablation lesions and activation mapping to demonstrate an activation detour from one side to another of the line.If AF still existed after the completion of CPVI (CPVI plus BB modifcation in the CPVI-BB group), direct current cardioversion would be performed to restore sinus rhythm.To determine the efect of BB modifcation on LAA activation, a Lasso or PentaRay mapping catheter was positioned within LAA after BB modifcation.LAA electric isolation was defned as the disappearance of all LAA potentials and dissociation of LAA electric activity from the LA during LAA ectopics or pacing from LAA [12].

Patient Follow-Up and Clinical
Outcomes.All patients were followed up at 3, 6, 9, and 12 months after the index procedure via telephone or hospital visit.An ECG was obtained at each follow-up point, and a 24-hour Holter ECG monitor was worn at the 3 and 12-month visits.In case of symptoms which suggested recurrent arrhythmia, an additional ECG or 24-hour Holter would be performed.All patients received antiarrhythmic drug (AAD) and anticoagulation for at least 3 months to avoid early recurrences and reduce the incidence of thromboembolic events.A proton pump inhibitor was given for at least 6 weeks.Te primary outcome was freedom from clinical recurrence of atrial arrhythmias at 12 months after the index procedure.Recurrence of atrial arrhythmias was defned as any documented episode of AF or atrial tachycardia lasting at least 30 s [2].Episodes of atrial arrhythmias within the frst 3-month blanking period after the index procedure were considered early recurrence, and only recurrence after the blanking period was diagnosed as clinical recurrence.After the blanking period, AADs were prescribed in cases where AF/AT recurrence or frequent atrial premature beats were documented by ECG or 24-h Holter ECG monitoring.Other outcomes included procedure-related complications like groin hematoma, LAA electric isolation, pericardial efusion and tamponade, left phrenic nerve injury, atrial esophageal fstula, and other safety endpoints such as stroke and death.Cardiology Research and Practice

Results
From In the propensity score-matched persistent AF cohort, 1 pericardial efusion and 1 pseudoaneurysm occurred in the CPVI group, and 1 pericardial efusion occurred in the CPVI-BB group (P �1.000).Te Kaplan-Meier estimate of freedom from any atrial arrhythmia recurrence at 12 months was 83.3% in the CPVI-BB group, signifcantly higher than that in CPVI group (70.2%,Log-rank P � 0.047, Figure 3).No signifcant diference was found in the incidence of AFL or AT between the CPVI group and CPVI-BB group in patients with persistent AF (Table 3).
In the propensity score-matched paroxysmal AF cohort, only 1 procedure-related complication, pericardial efusion, occurred in the CPVI-BB group.Tere was no diference in  BB modifcation in addition to CPVI was associated with a signifcant improvement in the maintenance of sinus rhythm for patients with persistent AF during the followup.However, as for patients with paroxysmal AF, the novel ablation approach did not improve the clinical outcome of RFCA.Second, BB modifcation did not increase the risk of procedure-related complications or iatrogenic arrhythmias caused by gaps in the ablation lines.

One-Year Clinical Outcomes of CPVI-BB in Patients with
Persistent AF.Te clinical outcome of patients with persistent AF is unsatisfying, and the optimal ablation approach is yet to be determined [13,14].It is noteworthy that BB modifcation in addition to CPVI results in 83.3% of patients with persistent AF being arrhythmia-free at one year, signifcantly higher than those who received CPVI only in our observations.Several recent trials investigating BB ablation in patients with persistent AF have produced similar results.De Martino et al. [5] described adjunctive BB ablation in the setting of hybrid ablation for longstanding persistent AF and found that one-year freedom from atrial arrhythmia recurrence rates in the BB group were superior to those without BB ablation.Similarly, substrate modifcation targeting the BB through an endocardial approach also acquires promising results [10].
Besides, other linear ablation strategies, which impaired Bachmann's bundle to some extent, such as "Dallas lesion" and the left atrial anterior linear lesion, proved efective in persistent AF [3,15].

Cardiology Research and Practice
Recently, increasing evidence demonstrates the role of interatrial conduction, including Bachmann's bundle, coronary sinus conduction, and septal conduction in the maintenance of AF [16,17].Lim et al. [16] found that complete disconnection of the right atrium (RA) and LA resulted in an 80% chance of AF termination within 60 s in computer simulations.Kumagai et al. [18] observed that AF could not sustain itself unless a septal reentrant circuit involving the atrial septum existed.In some cases, unstable (short-lived) reentrant circuits of short cycle length in LA were transmitted to RA via BB before reentering LA via other interatrial conduction pathways, and thus these circuits were maintained in both atria.Tese circuits might disappear when conduction via BB is blocked, even if not completely.

One-Year Clinical Outcomes of CPVI-BB in Patients with
Paroxysmal AF.During the follow-up, patients with paroxysmal AF who received additional BB modifcation were found not to be superior to those undergoing CPVI treatment, with a similar atrial arrhythmia recurrence at one year.Terefore, only 53 patients with paroxysmal AF received BB modifcation and BB modifcation were no longer performed on patients with paroxysmal AF.Different from persistent AF, the main mechanism of paroxysmal AF is regarded as triggered activity, predominantly originating in the PV antrum [19].Non-PV trigger accounts for no more than 10% of PAF trigger [20].In addition, CPVI not only eliminates triggers in the PV antrum but also afects the ganglionated plex or autonomic nerves [21].Consistent with our observation, additional ablation such as CAFE-guided ablation, roof line, posterior box lesion, and Dallas lesion did not improve the clinical outcomes of patients with paroxysmal AF [20,22,23].Since paroxysmal AF recurrence is usually caused by PV reconnection [24], permanent and complete CPVI is regarded as the cornerstone technique for the ablation of paroxysmal AF.

Procedure-Related Complications and Concern for Iatrogenic Arrhythmias.
Although prior studies raised the concern that BB's ablation could impair the function of the left atrium appendage and result in a higher incidence of thromboembolic events by delaying electrical activation of LAA [11,12], it is noteworthy that no LAA electric isolation and no complications specifcally related to BB modifcation were found in our observation.Similar results were observed in other trials, in which BB were ablated through an epicardial or endocardial approach [5,6].BB is not the exclusive route of interatrial conduction, and wavefront propagates to LAA along other interatrial pathways when conduction across BB is impaired [9].Besides concern for thromboembolic events, additional linear lesions, if incomplete, may be proarrhythmic [25].In our study, no diferences were found in the recurrence of atrial tachyarrhythmias, which difers from the results published by Sawhney et al. [25].A major diference between our study and that published by Sawhney et al. is that the liner lesion in our ablation approach is relatively short.Short lines of conduction block result in short conduction time to propagate around linear lesions, and initiation of reentry through gaps in the linear lesions may become difcult [26].

4.5.
Limitations.Several limitations should be acknowledged in the present study.First, this is a nonrandomized observational study, and the selection of the ablation approach was solely at the discretion of the operator.Although propensity score matching was performed to reduce selection bias, there may exist unmeasured confounding between treatment groups; what's more, patients with additional ablation for an identifed non-PV focus and/or large area of low voltage in the left atrium were excluded in the present study, and our results may not be applicable for these people; as a result, our fndings should be considered hypothetical and randomized controlled trials will be performed in the near future.Second, this study was performed at a single center and the external validity might be limited.However, overall freedom from atrial arrhythmias after CPVI treatment in patients with paroxysmal and persistent AF was consistent with those reported previously [13,20,27].Finally, the recurrence of atrial arrhythmias was mainly based on ECG and scheduled 24-h Holter monitoring; shortlasting episodes of paroxysmal AF which caused no symptom may have been underdiagnosed.

Conclusions
Compared with CPVI alone, CPVI with additional BB modifcation is associated with better clinical outcomes in patients with persistent AF, while in patients with paroxysmal AF, the efcacy is comparable, suggesting that Bachmann's bundle may play an important role in the perpetuation of AF.Further clinical trials are warranted to confrm our promising results.

Figure 3 :
Figure 3: Kaplan-Meier analysis of freedom from recurrence of atrial arrhythmias in matched persistent AF cohort.CPVI, circumference pulmonary vein isolation; BB, Bachmann's bundle.

Table 1 :
Baseline characteristics of patients with persistent AF.

Table 2 :
Baseline characteristics of patients with paroxysmal AF.

Table 3 :
Procedure results and clinical outcomes of patients with persistent AF after propensity score matching.
Figure 4: Kaplan-Meier analysis of freedom from recurrence of atrial arrhythmias in matched paroxysmal AF cohort.CPVI, circumference pulmonary vein isolation; BB, Bachmann's bundle.

Table 4 :
Procedure results and clinical outcomes of patients with paroxysmal AF after propensity score matching.