Atrial fibrillation (AF), a significant contributor to increased all-cause mortality [1], is associated with a heightened risk of stroke, heart failure, myocardial infarction, and cognitive decline. The mean annual hospitalization rate for AF patients is notably higher than that for individuals without AF [2]. Beyond impacting quality of life and health, AF imposes considerable economic and physical burdens. Catheter ablation, recognized as an effective strategy for managing AF, is endorsed in clinical guidelines as the primary treatment for individuals with paroxysmal AF and is also recommended for patients with persistent AF who respond poorly to antiarrhythmic medications [3, 4].

Although the electrophysiological mechanisms underlying AF require further investigation, it is widely accepted that ectopic beats emanating from the pulmonary veins frequently trigger AF episodes. Consequently, circumferential pulmonary vein isolation (CPVI) has emerged as a fundamental technique in AF ablation [5].

While CPVI is effective for paroxysmal AF, the recurrence rate remains high for persistent AF. Some initial studies have suggested that adding linear ablation outside the pulmonary veins could reduce recurrence in persistent AF ablation; however, the STAR AF II study challenged the efficacy of this additional procedure [6]. Recent advancements, such as the smart touch catheter and ablation index, have prompted further research into the benefits of additional linear ablation. The left atrial posterior wall, closely linked with the pulmonary veins, is often the site of significant non-pulmonary vein triggers in persistent AF [7]. Left atrial BOX ablation, which can isolate posterior left atrial (LA) by linear ablation of LA roof and bottom after PVI, could preventing AF triggers and help maintaining sinus rhythm [3]. Despite published randomized controlled trials (RCTs) on left atrial BOX ablation, the advantages of this additional procedure in patients with persistent AF remain debated. This meta-analysis seeks to assess the effects of supplementary left atrial BOX ablation on the recurrence and safety of persistent AF, to determine the safety and efficacy of left atrial BOX ablation, and to provide evidence supporting the use of catheter ablation to reduce recurrence rates in patients with persistent AF.

This meta-analysis evaluated six RCTs to compare the efficacy of CPVI combined with left atrial BOX ablation versus CPVI alone in treating persistent atrial fibrillation. The findings indicate that the combined approach did not markedly decrease the overall recurrence rate of atrial arrhythmias post-ablation. However, in subsets of patients with smaller left atrial diameters, this combination significantly reduced the recurrence of atrial arrhythmias and fibrillation. While the combined procedure extended both ablation and overall operation times, it did not elevate the risk of procedure-related complications, thereby affirming the safety and efficacy of left atrial BOX ablation.

CPVI is established as the foundational ablation technique for atrial fibrillation [5], owing to it being particularly effective in maintaining sinus rhythm in paroxysmal AF patients [14], albeit with a notable recurrence in persistent AF cases, where the recurrence rate post-CPVI has been documented at 43% [15]. Persistent AF patients often exhibit extensive atrial fibrillation and larger left atrial diameters, suggesting additional extrapulmonary triggers and mechanisms. Given the shared embryonic origin of the left atrial posterior wall and the pulmonary veins, ablating the posterior wall is a supported strategy [16]. Catheter ablation in persistent AF frequently reveals low-voltage areas in the posterior left atrial wall, where vagal ganglia plexuses contribute to the electrical and anatomical remodeling, making it a critical site for AF triggers and maintenance [17]. Left atrial BOX ablation, following CPVI, isolates the posterior wall by connecting the superior line, thereby enhancing safety due to its proximity to the esophagus and the presence of a thicker atrial muscle and fat pad [18, 19]. None of the six RCT studies included in this article had an atrial esophageal fistula. We provided images of BOX ablation and electrophysiology (EP) electroanatomic mapping (Fig. 9). The EP electroanatomic mapping was conducted before the ablation.

Fig. 9.

Image of BOX ablation and EP electroanatomic mapping. EP, electrophysiology; AP, anterior-posterior; PA, posterior-anterior; LAO, left anterior oblique; RAO, right anterior oblique; LL, left lateral; RL, right lateral; INF, inferior; SUP, superior.

This study found that additional left atrial BOX ablation in patients with smaller left atrial diameters could effectively lower the recurrence of atrial arrhythmias and AF. The correlation between the increase in left atrial diameter and the duration of AF suggests alternative triggers and mechanisms in post-structural remodeling, influencing the overall recurrence rate. Furthermore, based on our analysis, we can hypothesize that CPVI combined with BOX ablation may be effective in patients with paroxysmal atrial fibrillation. Thus, early detection and intervention could potentially reduce postoperative AF recurrence. Hence, patients with AF are advised to undergo early radiofrequency ablation to prevent left atrial enlargement and ensure a better prognosis and lower recurrence.

Regarding ablation duration, left atrial BOX ablation lengthened the ablation and total procedure times compared to PVI alone. However, the study by Kistler et al. [13] demonstrates that additional BOX ablation would not be prolonged with a high power short time course ablation strategy. Moreover, the high-power short-range ablation strategy can reduce the recurrence rate of atrial fibrillation after left atrial BOX ablation [20].

The review included six studies encompassing 967 patients, thereby representing a relatively small sample size. Although the results indicate that CPVI combined with BOX ablation significantly reduces the recurrence rate of arrhythmias in patients with left atrial diameter $\le$44 mm, the small sample size may affect the robustness of these findings. Consequently, further research involving a larger cohort is essential. Additionally, it is necessary to conduct studies to confirm the effectiveness of CPVI combined with BOX ablation in patients with larger LAD.

The six studies in this analysis followed CPVI with additional linear ablation, encompassing the mitral isthmus line, tricuspid isthmus line, and anterior wall lines. However, the variability in ablation practices across different centers and among operators precluded a detailed analysis of the impact of these additional ablations on recurrence rates.

Adopting advanced cold saline infusion pressure-sensing ablation catheters, which are now prevalent, was inconsistent due to the varying trial timelines. Consequently, the influence of the catheter selection on the recurrence of atrial fibrillation could not be assessed.

Of the six studies, only the Kistler et al. [13] study employed high-power and AI-guided ablation, while the remaining five utilized lower ablation powers and did not report AI parameters at different ablation sites. Additionally, avoiding a bidirectional block on the posterior wall line due to concerns over the risk of atrial–esophageal fistula may have influenced outcomes. Future studies employing high-power, short-duration, AI-guided ablation strategies that achieve a bidirectional block on the modified posterior wall line may demonstrate a lower recurrence rate post-CPVI combined with left atrial BOX ablation.

The primary outcome of the included studies was the recurrence rate of all atrial arrhythmias one year after operation; however, the recurrence rates over longer follow-up periods remain unspecified. Therefore, future research should extend the follow-up duration beyond one year to better assess the long-term outcomes.

In patients with persistent AF, CPVI combined with left atrial BOX ablation did not substantially reduce the recurrence rate compared to CPVI alone. Nevertheless, for patients with a smaller left atrial diameter, this combined approach significantly enhanced the success of catheter ablation for persistent AF, reducing the recurrence of atrial arrhythmias and fibrillation without increasing the risk of surgical complications. Left atrial BOX ablation proved both effective and safe. Further RCTs with standardized AF ablation protocols are essential to corroborate these results.

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

AF, atrial fibrillation; AA, atrial arrhythmia; AT, atrial tachycardia; AFL, atrial flutter; CPVI, circumferential pulmonary vein isolation; RCT, randomized controlled trial; CI, confidence interval; RR, relative ratio; WMD, weighted-mean difference; AI, ablation index; LSI, lesion size index.

YL and JH designed the research study. YL and YX performed the research. WYZ collated the data. YX performed the statistical analysis and interpreted the results. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/j.rcm2509316.