Cryoballoon ablation of the left atrial posterior wall reduces recurrence of persistent atrial fibrillation in patients with non‐paroxysmal atrial fibrillation

Abstract Background This study aimed to clarify the clinical outcomes of cryoballoon ablation of the left atrial (LA) posterior wall (LAPW), including the LA roof, in patients with non‐paroxysmal atrial fibrillation (AF). Methods We analyzed the outcomes of 284 patients with non‐paroxysmal AF, of whom 210 underwent the cryoballoon ablation of the LAPW, including the LA roof, in addition to pulmonary vein isolation with a cryoballoon. Results Complete conduction block at the LA roof was obtained in 95.7% (201/210) of patients, and LAPW was isolated in 83.3% (130/156) of patients. Over 372 (range, 208–477) days of follow‐up, atrial arrhythmia recurrence was observed in 84 (29.6%) patients, and atrial tachycardia (AT) recurrence accounted for 27.4% of cases. The prevalence of LA roof cryoballoon ablation was significantly higher in patients without recurrence than in those with recurrence (78.6% vs. 63.1%, respectively; p = .01), especially those with persistent AF recurrence (77.0% vs. 55.0%, p = .01). No significant difference was found in the prevalence of AT recurrence between patients who had undergone additional LAPW ablation and those who had not. Durable LA roof lesions were confirmed in 29 (72.5%) of 40 patients who underwent redo ablation. Conclusions Cryoballoon ablation of the LAPW leads to a sufficient acute success rate of complete conduction block and durable lesions of the LA roof without increasing AT recurrence risk. The prevalence of persistent AF recurrence decreases after additional cryoballoon ablation of the LAPW in patients with non‐paroxysmal AF.


| INTRODUC TI ON
The recurrence of atrial fibrillation (AF) can be controlled by the established treatment of pulmonary vein isolation (PVI) 1 ; however, the effect of PVI appears to be insufficient in patients with nonparoxysmal AF. Additional strategies for AF catheter ablation have been considered in previous investigations, and linear ablation of the left atrial (LA) roof line and mitral isthmus (MI) line is one of the additional therapeutic methods of catheter ablation. 2 Atrial tachycardia (AT) recurrence has been reported as an undesirable outcome after catheter ablation for AF, which might be attributable to linear ablations. 3 Ablation of the LA roof with a cryoballoon in addition to PVI was investigated as a novel method for LA roof line ablation. 4 However, detailed clinical outcomes, including the type of recurrence, have not been fully examined. Thus, this study aimed to clarify the details after catheter ablation in patients with non-paroxysmal AF, especially those who underwent the cryoballoon ablation of the LA posterior wall (LAPW), including the LA roof.

| Study patients
This single-center retrospective study included consecutive patients with non-paroxysmal AF who underwent cryoballoon ablation with PVI between September 2014 and June 2019. Patients who underwent heart surgery were excluded because the surgery could have contributed to the AT occurrence. Patients who underwent LA roof line or LAPW bottom line ablation using a radiofrequency (RF) catheter were also excluded because the effect of the ablation was considered to vary between LA roof line or LAPW bottom line ablation performed with a cryoballoon and that performed with an RF catheter. Patients who did not undergo clinical follow-up of more than 3 months were excluded from the analysis. We hypothesized that LAPW ablation, including cryoballoon ablation of the LA roof in addition to PVI, is effective in reducing the recurrence of persistent AF in patients with non-paroxysmal AF without inducing AT. To compare the effect of additional LAPW ablation with that of only applying PVI, only patients who did not undergo MI ablation were analyzed.
All patients underwent three-dimensional computed tomography and transthoracic echocardiography before ablation. Paroxysmal AF was defined as AF terminating within 7 days according to the previously reported definition 5 ; hence, non-paroxysmal AF was defined as AF persisting for more than 7 days. Baseline demographic characteristics, comorbidities, and medications were recorded.

| Index ablation procedure
The ablation procedure was performed as previously described. 6 Briefly, the procedure was performed under general anesthesia. A single transseptal puncture was made under fluoroscopic and intracardiac echocardiographic (Acuson and AcuNav; Biosense Webster) guidance. A 28-mm cryoballoon catheter (Arctic Front Advance; Medtronic) was introduced into the LA through a steerable sheath (Flexcath Advance; Medtronic) with a circular mapping catheter (Achieve; Medtronic). Cryothermal energy was applied through a cryoballoon occluding each pulmonary vein (PV). The compound motor action potentials of the diaphragm provoked by phrenic nerve pacing were continuously monitored during ablation of the right PVs.
When a successful PVI was not achieved solely by a cryoballoon, a touch-up ablation with an RF catheter (FlexAbility or TactiCath; Abbott) was performed.
Additional ablations were performed according to the operator's decision. When LA roof cryoballoon ablation was performed, an Achieve catheter was inserted into the left and right superior PVs, and a cryoballoon was shifted along the LA roof by chang- with a cutoff value of 15°C. RF applications were also prematurely interrupted when the LET reached 39°C. Linear ablation at the cavotricuspid isthmus (CTI) was performed by delivering RF energy from the tricuspid annulus to the inferior vena cava in a point-bypoint fashion. After each linear ablation, the status of the conduction block was confirmed by an electrophysiological method, an activation map, and a voltage map created with an electrical impedance-based mapping system (Ensite NavX; Abbott). PVI was confirmed using a duodecapolar circular mapping catheter (EPstar Libero; Japan Lifeline). The voltage map before and after the ablation procedure of the representative cases is depicted in Figure 1.

| Clinical follow-up
Anti-arrhythmic drugs (AADs) were prescribed after ablation at the discretion of the patient's attending cardiologist. Twelve-lead electrocardiograms (ECGs) were recorded at every follow-up visit or an emergency visit owing to symptoms suggestive of an arrhythmia recurrence. In addition, 24-hour Holter ambulatory ECG monitoring was performed to detect the recurrence of paroxysmal arrhythmias.
An arrhythmia recurrence was defined as any documented atrial arrhythmia lasting longer than 30 s after the initial 90-day blanking period.

| Redo ablation procedure
The repeat ablation procedure was performed in a manner similar to the index one. When AT persisted at the beginning of the procedure, it was mapped using an EPstar Libero and Ensite NavX system. Along with electrophysiological findings, catheters and systems were used to confirm the status of the lesions created in the index ablation procedure. Based on the operator's judgment, ablation was performed for novel or recurring lesions.   Table 1 and compared between patients who underwent only PVI with a cryoballoon, those who underwent cryoballoon ablation of the LA roof in addition to PVI, and those who

| Index ablation results
The procedural characteristics during the ablations are shown in Table 1 Touch-up ablation with RF energy was performed in 10 patients  (Table 3).

| Clinical outcomes
The median follow-up duration was 372 [interquartile range, 208-477] days. Atrial arrhythmia recurrence was observed in 84 (29.6%) of 284 patients, and the 12-month Kaplan-Meier event-free rate was 75.6% ( Figure 2). Of 284 patients, AT and AF recurrence were confirmed in 23 (8.1%) and 68 (23.9%) patients, respectively. The persistent type accounted for 58.8% of AF recurrences (40/68 patients). Table 1 shows the comparisons between patients based on recurrence, with each recurrence pattern in addition to overall recurrence. The prevalence of LA roof line ablation and additional

| Redo ablation results
Among the 84 patients exhibiting recurrence after the index cath-  The durability of each lesion created in the index ablation procedure is described in Figure 4.

| DISCUSS ION
This study investigated the details after catheter ablation in patients with non-paroxysmal AF, particularly those who underwent LAPW cryoballoon ablation, including the LA roof. The main results showed that cryoballoon ablation of the LAPW was not associated with a high incidence of ATs during follow-up. An LA roof-dependent AT was observed in only 1.4% of the patients. Moreover, clinical outcomes were improved after the ablation procedure was compared with the strategy without LAPW ablation, especially regarding the recurrence of the persistent type of AF. Details of recurrence patterns, including the type of AT, and the durability of lesions created in the index ablation procedure were also investigated in this single-center large cohort study. Further studies might be required to assess atrial function after the ablation more precisely and select candidates who should undergo the cryoballoon ablation of the LAPW.
One of the reasons for hesitation in performing linear ablation was the possibility of iatrogenic AT occurrence after the ablation procedure. After PVI, including both RF energy and cryoballoon ablation, AT recurrence was observed in approximately 10% of the patients, according to previous reports. [19][20][21] In a study that compared the prevalence of AT recurrence between patients who underwent PVI with RF energy and those who underwent PVI with a cryoballoon, the AT recurrence rate tended to be lower in those who underwent PVI with a cryoballoon. 19  Our study had a few limitations. First, this was a single-center, non-randomized retrospective study. Therefore, the results regarding additional cryoballoon ablation of the LAPW should be carefully interpreted, although no significant differences were found in patient characteristics such as LAD or the existence of left common PV or right middle PV between patients who underwent cryoballoon ablation of the LAPW and those who did not. Finally, the use of AADs after the index ablation was also different among study patients; thus, clinical follow-up data require prudent interpretations.
A randomized multicenter study with a fixed protocol is necessary to confirm the efficacy and influence of LAPW ablation with a cryoballoon. Nonetheless, we presented detailed data in terms of acute and long-term success rates and clinical outcomes after ablation, including the recurrence type. We consider that these findings will contribute to further examinations regarding cryoballoon ablation of the LAPW in the future.

| CON CLUS IONS
In this study, the efficacy of cryoballoon ablation for the LAPW, especially at the LA roof, was demonstrated. A sufficient success rate of complete conduction block at the LA roof, including the chronic durability of the lesions, can be expected. AT recurrence after ablation does not increase in patients who undergo cryoballoon ablation of the LAPW. The recurrence rate of the persistent type of AF after ablation becomes lower when cryoballoon ablation of the LAPW is performed.
The conversion from the persistent to the paroxysmal type after ablation may have various benefits. The risk of stroke or heart failure might be reduced, and complete elimination of AF might be possible after an additional trigger-based ablation. Therefore, the strategy of LAPW ablation could lead to better clinical outcomes after ablation in patients with non-paroxysmal AF who would not benefit from PVI alone. However, identifying suitable candidates for additional LAPW ablation remains to be clarified.

ACK N OWLED G M ENTS
We would like to thank Editage (www.edita ge.com) for the English language editing.

CO N FLI C T S O F I NTE R E S T
Authors declare no conflict of interests for this article.

E TH I C S D I SCLOS U R E
The protocol for this research project has been approved by a suit-