The Value of Adjunctive Left Atrial Posterior Wall Isolation on Clinical Outcomes in Atrial Fibrillation Patients: a systematic review and meta-analysis

doi:10.21203/rs.3.rs-3599503/v1

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Research Article

The Value of Adjunctive Left Atrial Posterior Wall Isolation on Clinical Outcomes in Atrial Fibrillation Patients: a systematic review and meta-analysis

https://doi.org/10.21203/rs.3.rs-3599503/v1

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Background

Although pulmonary vein isolation (PVI) remains the cornerstone of atrial fibrillation (AF) ablation. The left atrium posterior wall is an arrhythmogenic substrate that contributes to the development of AF. It remains unclear whether additional left atrial posterior wall isolation (LAPWI) beyond PVI is beneficial in AF patients. This study evaluated the impact of PWI on clinical outcomes of AF patients.

Methods

PubMed, EMBASE, and Cochrane Library databases were searched for studies comparing the outcomes of AF with and without PWI. The efficacy outcomes were recurrence of all atrial arrhythmia (AA), atrial fibrillation (AF), and atrial flutter (AFL)/atrial tachycardia (AT). The safety outcomes were mainly focused on procedural adverse events.

Results

A total of 16 studies (7 RCTs, 3 prospective study and 6 retrospective analysis) with 3340 patients with AF were included (1550 patients in PVI with PWI group and 1790 in PVI alone group). 12 studies included persistent atrial fibrillation patients, 3 studies with paroxysmal AF patients and 1 study with paroxysmal AF and persistent AF concurrently. Mean follow-up was 16.56months. In AF patients, adjunctive PWI obviously reduced the recurrence of all atrial arrhythmias (RR 0.78 [95% CI 0.64–0.95], I²=79%, P=0.01) and the recurrence of AF (RR 0.68 [95% CI 0.53–0.88], I²=75%, P=0.004); Meanwhile, adjunctive PWI was not associated with substantially lower recurrence of atrial flutter (AFL)/atrial tachycardia (AT) (RR 1.23 [95% CI 0.94–1.60], I²=49%, P=0.12) .The incidence of procedural adverse events between the PVI only and PWI+PVI was similar (RR 1.19 [95% CI 0.80–1.79], I²=0%, P=0.39). In subgroup analyses, the benefit of adjunctive PWI compared with PVI only was more significant in persistent AF group and cryoballoon ablation group. Notably, adjunctive PWI with radiofrequency ablation may induce a slight increase of recurrent AFL/AT compared with PVI only (RR 1.56 [95% CI 1.02–2.39], I²=30%, P=0.04).

Conclusions

In patients with AF, adjunctive PWI was associated with decreased recurrence of AF and atrial arrhythmias compared with PVI alone without an increased risk of procedural adverse events, especially in persistent AF patients. Cryoballoon ablation seemed more suitable for PWI compared with radiofrequency ablation. More RCTs are needed to verify the conclusion.

Atrial Fibrillation

Left Atrial Posterior Wall Isolation

Pulmonary Vein Isolation

Atrial fibrillation (AF) is the most common supraventricular arrhythmia in adults, affecting approximately 43.6 million individuals globally. It is associated with a series of cardiovascular adverse events and high mortality[1, 2]. Catheter ablation has emerged as an effective rhythm control strategy for AF, demonstrating benefits in preventing arrhythmia recurrence, improving quality of life, and reducing mortality in symptomatic AF patients, as supported by previous research[3–6]. Recent guidelines have endorsed catheter ablation as a first-line therapy and superior alternative to antiarrhythmic drugs (AADs) for maintaining sinus rhythm and improving symptoms in select patient populations[2].

Currently, pulmonary vein isolation (PVI) is considered the cornerstone ablation strategy widely used for AF treatment[2]. However, the success rate of maintaining sinus rhythm after PVI remains relatively low, especially in patients with persistent AF (Per-AF)[7, 8]. Left atrial posterior wall isolation (PWI), as an extensive ablation strategy, has been proposed in addition to PVI to target non-pulmonary vein triggers[2]. Previous trials have suggested that adjunctive PWI may yield better clinical outcomes compared to PVI alone[9, 10]. However, the CAPLA study reported that adding PWI to PVI did not significantly improve outcomes when compared to PVI alone[11]. The efficacy of adjunctive PWI remains a topic of debate. Given this knowledge gap, we conducted a systematic meta-analysis of the most recent clinical studies, encompassing both randomized controlled trials (RCTs) and non-RCTs, to provide insights into the role of adjunctive PWI in AF patients.

Search strategy and data extraction

We executed the meta-analysis in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (as seen in Table 1of the Supplement)[12]. Our study protocol has been officially registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202380127). The full document can be accessed at inplasy.com (https://inplasy.com/inplasy-2023-8-0127).

Table 1

Patient baseline characteristics in the Meta-Analysis
Author/year	Design type	AF Type	Total Patients		Female,n(%)		Mean age		LAD mm
			PVI	PVI + PWI	PVI	PVI + PWI	PVI	PVI + PWI	PVI	PVI + PWI
Arash2021	RCT	perAF	55	55	22(40)	20(36)	70 ± 9	67 ± 8	44 ± 5	44 ± 4
Kistler2023	RCT	perAF	168	170	40 (23.8)	39 (22.9)	65.5 (57.8–71.7)	65.7 (58.7–71.1)	44 ± 7	46 ± 0.6
Kim2015	RCT	perAF	60	60	19 (31.7)	60 (23.3)	58.3 ± 9.6	56.2 ± 11.9	42.1 ± 5.1	42.3 ± 6.4
Ahn2022	RCT	perAF	50	50	5 (10)	11 (22)	65.9 ± 8.8	65.1 ± 8.6	48.5 ± 8.1	48.1 ± 7.4
Murata2022	Prospective study	perAF	212	212	71 (20.1)	58(26.6)	64.3 ± 10.2	67.7 ± 9.5	42.3 + 6.2	42.2 + 7.0
Pak2020	RCT	perAF	57	57	17 (29.8)	15 (26.3)	61.6 ± 7.8	58.6 ± 11.4	42.7 ± 6.1	41.4 ± 6.1
Daehoon2022	RCT	PAF + PerAF	75	75	13 (17.3)	22 (29.3)	59.1 ± 9.9	60.0 ± 9.9	41.0 ± 5.8	41.7 ± 7.1
tokioka2021	retrospective study	perAF	91	90	19(20.9)	23(25.6)	66.9 ± 10.6	67 ± 9.9	42.5 ± 7.1	42.4 ± 6.2
Jankelson2021	retrospective study	PAF	214	107	69 (32.2)	38(35.5)	60.7 ± 11.7	63.3 ± 11	27 (23, 31)	26 (21, 31)
Bisignani2020	retrospective study	PAF	50	30	21(42)	10(33.3)	67.4 ± 8.5	68.4 ± 9.16	43.9 ± 9.5	44.8 ± 4.7
Aryana2018	prospective study	perAF	168	222	60 (36)	76 (34)	67 ± 11	67 ± 9	44 ± 7	47 ± 9
Bai2015	prospective study	perAF	20	32	4(20)	5(16)	63 ± 11	64 ± 10	49 ± 4	48 ± 7
Sutter2019	retrospective study	perAF	255	78	84(33)	25(32)	67(59–73)	66(56–74)	42 ± 7	46 ± 7
Nishimura2019	retrospective study	perAF	50	50	8(16)	8(16)	66 ± 10	62 ± 10	43 ± 6	44 ± 5
Lee2019	RCT	perAF	105	102	21(20)	14(13.7)	58.6 ± 11	58.9 ± 10.5	44.5 ± 6.7	45 ± 5.3
Aryana2023	retrospective study	PAF	160	160	54(34)	61(38)	63 ± 11	63 ± 10	44 ± 7	44 ± 5
RCT = randomized controlled trial; AF = atrial fibrillation; PVI = pulmonary vein isolation; PWI = posterior left atrial wall isolation; LAD = left ventricular posterior; PAF, paroxysmal atrial fibrillation; PerAF, persistent atrial fibrillation.

A comprehensive search was undertaken in PubMed, EMBASE, and the Cochrane Central Register of Clinical Trials (CENTRAL) for RCTs that assessed the efficacy of adjunctive left atrial posterior wall isolation on the clinical outcomes of patients with atrial fibrillation up until August 30, 2023. We did not limit our search by language. To augment this search, we also performed a manual search of reference lists from pertinent articles and guidelines issued by professional societies. The detailed literature search strategy can be found in the supplement (Table 2in Supplement). Studies were included if they met the following criteria: (1) Patients with atrial fibrillation. (2) Additional left atrial posterior wall isolation (LAPWI) beyond pulmonary vein isolation (PVI) or PVI only was performed of these patients. (3) Outcomes Indicators: recurrence of all atrial arrhythmia (AA), atrial fibrillation (AF), atrial flutter (AFL) / atrial tachycardia (AT) and procedural adverse events, including one.

Table 2

Patient procedure characteristics in the Meta-Analysis
Author/year	Main ablation	Procedure time		Ablation Time		Fluoroscopy time		Follow-up
		PVI	PVI + PWI	PVI	PVI + PWI	PVI	PVI + PWI
Arash2021	CBA	127 ± 40	168 ± 34	29 ± 14	51 ± 15	NR	NR	12
Kistler2023	RF	120.5 ± 56.8	142 ± 69.3	28 ± 11.7	34.2 ± 20.7	10.5 ± 7.2	11.5 ± 6.8	12
Kim2015	RF	154.9 ± 57.1	163.1 ± 47.2	121.7 ± 58.7	128.9 ± 37.9	NR	NR	12
Ahn2022	CBA	74.3 ± 8.9	98.8 ± 6.2	25.8 ± 3.1	38.8 ± 5.1	4.6 ± 2.6	6.1 ± 4.7	12
Murata2022	RF	NR	NR	NR	NR	NR	NR	12
Pak2020	RF	179.1 ± 60.2	186.2 ± 52.7	69.79 ± 15.87	88.94 ± 25.28	NR	NR	23.8 ± 10.2
Daehoon2022	RF	101(86–121)	120(100–138)	18.06(13.23–27.73)	26.58(20.73–38.37)	NR	NR	17
tokioka2021	RF	NR	NR	NR	NR	NR	NR	19
Jankelson2021	RF	128 ± 29	125 ± 28	26.7 ± 8.7	28.6 ± 10.4	12.3 ± 7.8	14.8 ± 7.4	12
Bisignani2020	CBA	58.42 ± 16.62	93.56 ± 21.98	NR	NR	14.7 ± 7.4	25.23 ± 13	12
Aryana2018	CBA	97 ± 29	188 ± 42	Not reported	Not reported	19 ± 7	28 ± 9	12
Bai2015	RF	204 ± 96	216 ± 66	74 ± 40	88 ± 41	58 ± 29	62 ± 26	36
Sutter2019	RF	NR	NR	52 ± 28	53 ± 21	NR	NR	6
Nishimura2019	CBA	192 ± 33	153 ± 52	NR	NR	NR	NR	12
Lee2019	RF	206.8 ± 77.7	226.7 ± 63.1	71.48 ± 30.61	89.41 ± 39.3	35 ± 18.2	38 ± 16.6	16.2 ± 8.8
Aryana2023	CBA	103 ± 24	127 ± 14	23 ± 10	42 ± 11	13 ± 8	20 ± 6	39 ± 9
PVI = pulmonary vein isolation; PWI = posterior left atrial wall isolation; RF = radiofrequency ablation; CBA = cryoballoon ablation.

The protocol was carefully crafted by two authors (Lianfeng Liu and Yu Geng) and subsequently reviewed by all co-authors. For document management, we employed the EndNote software (Version X9). Two investigators (Lianfeng Liu and Yu Geng) independently assessed the suitability of the identified studies, with any disagreements being resolved through discussion with the senior author (Ping Zhang).

Outcomes

The primary outcome encompassed the recurrence of all forms of atrial arrhythmia, atrial fibrillation, atrial flutter/atrial tachycardia. Secondary outcomes targeted was a composite endpoint of safety outcomes, mainly including procedural adverse events. We reviewed definitions employed in individual trials and aimed to use a consistent definition across trials wherever feasible (Refer to Supplemental Table 3). The Cochrane Collaboration criteria were utilized to assess the risk of bias in each incorporated study[13]

Statistical analysis

The meta-analysis was conducted using Revman5.3. For data that exhibited homogeneity (P > 0.10 and I2 ≤ 50%), a fixed-effect model was applied for the meta-analysis. In cases where homogeneity was not achieved (P > 0.10 and I2 ≤ 50%), and heterogeneity could not be disregarded, a random-effects model was utilized for combining effects[14]. Notably, sensitivity and subgroup analyses should be contemplated when analyzing this type of data. For continuous outcomes, we estimated the mean differences (MD) and the associated 95% confidence intervals (CIs). Several RCTs presented the median as the measure of treatment efficacy, along with the interquartile range (IQR). In such cases, we deduced the mean from the median and estimated standard deviations (SDs) from the IQR using methodologies from earlier research[15]. A p-value of < 0.05 was deemed statistically significant.

Subgroup and Sensitivity Analyses

The therapeutic efficacy and safety of adjunctive left atrial posterior wall isolation beyond pulmonary vein isolation as compared to only pulmonary vein isolation were scrutinized in patients diagnosed with atrial fibrillation. However, the type of atrial fibrillation and the ablation energy differed among the studies. Supplementary subgroup analyses were carried out to compare the efficacy and safety between the paroxysmal AF patient group and the persistent AF patient group, and between the radiofrequency ablation group and the cryoballoon ablation group. Revman was employed to determine the impact of individual studies on the aggregate pooled estimate for each predefined outcome.

The study selection process is summarized in the flow chart (Fig. 1). We identified a total of 1,499 studies from our search across PubMed, Cochrane Central Register for Controlled Trials, and EMBASE. Among these, 929 were excluded due to duplication. Further scrutiny of titles and abstracts led to the exclusion of another 551 studies. After a full-text review of the remaining 19 studies, 16 trials that evaluated the efficacy and safety of adjunctive left atrial posterior wall isolation for patients with atrial fibrillation were selected for inclusion.

Ultimately, the analysis encompassed 16 trials with 3340 patients: 1550 patients were allocated to the PVI with PWI group and 1790 to the PVI alone group (Tables 1 and 2). Table 1 summarizes patient baseline characteristics, and Table 2 describes procedure characteristics. Among them, Jankelson et al[16], Bisignani et al[17] and Aryana et al[18] included only paroxysmal AF patients (totally 721 patients enrolled). Daehoon et al[19] simultaneously enrolled paroxysmal and persistent AF patients (91 patients included was PAF with 53% in PVI group). The others left contained only persistent AF patients (totally 2469 patients enrolled). When it comes to the ablation method, those trials applying cryoballoon ablation as the main ablation energy included Arash et al[10], Ahn et al[9], Bisignani et al[17], Aryana et al[20] Nishimura et al[21] and Aryana et al[18] (totally 1100 patients included). The rest mainly with radiofrequency ablation. The mean follow-up time was about 16.56 months. No differences were observed in terms of the proportion of patients lost to follow up between the PVI and PVI plus PWI groups across trials.

Clinical outcomes

Patients assigned to the PVI with PWI group, when compared to the PVI alone group, demonstrated reduced odds of the recurrence of AA (RR 0.78 [95% CI 0.64–0.95], I²=79%, P = 0.01) (Fig. 2A). This was especially evident in the recurrence of AF (RR 0.68 [95% CI 0.53–0.88], I²=75%, P = 0.004) (Fig. 2B). However, no significant differences were observed between the groups in the recurrence odds of AT/AFL (RR 1.23 [95% CI 0.94–1.60], I²=49%, P = 0.12) (Fig. 2C). Similarly, the odds of adverse events (RR 1.19 [95% CI 0.80–1.79], I²=0%, P = 0.39) did not significantly differ between the two groups (Fig. 2D).

Subgroup analysis

We conducted a predetermined subgroup analysis based on the type of AF. Of the patients, 721 had paroxysmal AF (297 in the PVI with PWI group and 424 in the PVI alone group), while 1945 had persistent AF (916 in the PVI with PWI group and 1,029 in the PVI alone group).

There was no notable difference in odds of the recurrence of AA (RR 0.71 [95% CI 0.45–1.12], I²=62%, P = 0.14) and AF recurrence (RR 0.79 [95% CI 0.41–1.50], I²=65%, P = 0.47) for paroxysmal AF patients between the groups. However, for persistent AF patients, the PVI with PWI group showed decreased odds of the incidence of recurrent of AA (RR 0.77 [95% CI 0.61–0.98], I²=82%, P = 0.03) and AF recurrence (RR 0.65 [95% CI 0.47–0.90], I²=80%, P = 0.009) (Figure S1).As to the incidence of the recurrent AFL/AT and procedural complications, the additional PWI to PVI made no difference in both paroxysmal and persistent AF patients.

Furthermore, we conducted a subgroup analysis based on the ablation energy. Of the patients, 1,020 underwent cryoballoon ablation (537 in the PVI with PWI group and 483 in the PVI alone group), while 2,120 underwent radiofrequency ablation (923 in the PVI with PWI group and 1,197 in the PVI alone group). The cryoballoon ablation patients in the PVI with PWI group showed reduced odds of the recurrence of AA (RR 0.57 [95% CI 0.49–0.66], I²=0%, P < 0.001) and AF recurrence (RR 0.51 [95% CI 0.42–0.62], I²=0%, P < 0.001). However, no significant differences in odds were observed among the radiofrequency ablation patients between the groups for the incidence of recurrent of AA (RR 0.93 [95% CI 0.75–1.15], I²=74%, P = 0.49) and AF recurrence (RR 0.81 [95% CI 0.60–1.09], I²=72%, P = 0.16) (Figure S2). Interestingly, a mild increase of the incidence of recurrent AFL/AT happened in the radiofrequency ablation patients with adjunctive PWI (RR 1.56 [95% CI 1.02–2.39], I²=30%, P = 0.04), while no significant differences in cryoballoon ablation subgroup (RR 1.12 [95% CI 0.42–2.98], I²=61%, P = 0.82). Both in cryoballoon and radiofrequency groups, adjunctive PWI after PVI did not affect the safety outcomes.

Sensitivity analysis

Utilizing Revman, we assessed the influence of each individual study on the overall pooled estimates for each predefined outcome. Our findings suggest that the exclusion of any specific study would not significantly alter the results. Likewise, there were no substantial differences in other efficacy and safety outcomes. Sensitivity analysis using the Mantel-Haenszel fixed effects models with RR as the effect measure produced congruent findings (Supplemental figure S3).

Risk of bias and quality assessment of outcomes

The results of the risk of bias assessment with the RoB2 of randomized control trials are summarized in Supplement Figure S4. Six studies were considered at low risk for overall risk of bias.

To the best of our knowledge, this is the most recent systematic review and meta-analysis of RCTs and non-RCTs investigating the clinical outcomes of PWI as an adjunctive strategy in catheter ablation for AF patients. Our meta-analysis results revealed that the addition of PWI to PVI led to a lower incidence of recurrent atrial fibrillation (AF) and atrial arrhythmias (AA) in AF patients compared to PVI alone. Meanwhile, adjunctive PWI was not associated with any additional benefit in reducing the recurrence of atrial flutter or atrial tachycardia. In terms of safety endpoints, there was no significant difference in adverse events between the adjunctive PWI group and the PVI alone group. Subgroup analysis indicated that the reduction in the recurrence of AF and AA was more significant in subgroups of persistent AF and cryoballoon ablation (CBA) compared to paroxysmal AF and radiofrequency ablation (RFA) groups. Similar to the main findings, no differences in adverse event incidence were observed when stratified by AF type or ablation strategy. Interestingly, when RFA was used for catheter ablation, the recurrence of atrial flutter/atrial tachycardia was higher than in the CBA group. Additionally, the incidence of atrial flutter/atrial tachycardia after ablation was similar between the persistent AF and paroxysmal AF groups.

Role of the Left Atrial Posterior Wall in Atrial Fibrillation

Catheter ablation is considered a safe and effective alternative for maintaining sinus rhythm and improving symptoms in AF patients, when performed by experienced operators. PVI is commonly recommended as the primary ablation strategy for AF[2]. However, the efficacy of PVI alone is insufficient for achieving optimal clinical outcomes, particularly in patients with persistent and long-standing persistent AF[2, 22]. A meta-analysis reported a 12-month arrhythmia-free survival rate of only 66.7% when PVI alone was used as a single procedure in persistent and long-standing persistent AF[8]. Consequently, adjunctive PWI to PVI has been advocated as a strategy to enhance clinical outcomes in AF patients[23, 24].

Previous studies have demonstrated the presence of AF triggers outside the pulmonary veins (PVs)[25, 26]. When paroxysmal AF progresses to persistent or long-standing persistent AF, non-PV locations become more relevant, particularly in the posterior wall[27]. The left atrial posterior wall has been identified as an important source of non-PV triggers, with 38% of non-PV triggers originating from this region[25, 28]. Embryologically, anatomically, and electrophysiologically, the posterior left atrial wall is closely related to the PVs and shares a common tissue origin[29]. This connection allows the left atrial posterior wall to serve as a site for AF triggers. Myocytes in the left atrial posterior wall contribute to sustaining AF due to their electrophysiological properties, characterized by short action potential duration, the shortest refractory period, and a low resting membrane potential[30]. Furthermore, differences in the orientation of myocardial fibers in the left atrial posterior wall compared to the PVs can lead to local re-entry circuits[31]. Additionally, the presence of ganglionated plexi, which are abundant in the left atrial posterior wall, may play a role in initiating and sustaining AF[32].

As described above, the left atrial posterior wall is acknowledged as a key substrate in the initiation and maintenance of AF. Based on this, the additional posterior wall ablation adjunctive to PVI may improve the clinical outcomes of AF, especially reduce the recurrence of atrial arrhythmias, which is in keeping with the findings of our meta-analysis. However, the value of adjunctive PWI in improving AF prognosis remains a topic of debate. Recent meta-analyses have shown that concomitant PWI is associated with reduced recurrence of AF and all atrial arrhythmias after ablation, without an increased risk of post-ablation atrial flutter/atrial tachycardia, particularly in persistent AF patients[33–36]. However, the CAPLA study, the most recent RCT, reported that adding PWI to PVI alone did not significantly reduce the recurrence of atrial arrhythmias at 12 months compared to PVI alone after the first-time catheter ablation in persistent AF patients. Kistler et al. suggested that not all persistent AF patients may benefit from adjunctive PWI, and certain patient subgroups with specific characteristics, such as low voltage or longer-standing AF, may experience greater benefits[11]. Further trials, especially RCTs, are needed to determine which patient groups and endpoints are most suitable for adjunctive PWI.

Role of adjunctive PWI in paroxysmal and persistent AF

According to the results of our subgroup analysis, PWI can reduce the recurrence of AF or atrial arrhythmia in persistent AF, but it did not show to have additional benefit to PVI in paroxysmal AF. These retrospective analyses related to paroxysmal AF were included. Jankelson et al and Bisignani et al held the idea that Addition of PWI to PVI in paroxysmal AF patients after ablation did not reduce the frequency of atrial arrhythmia recurrence[16, 17]. Bisignani et al mentioned that there would be a very wide lesion around the PVs, often extending beyond the antrum and comprising a large portion of the LAPW when using CBA, which might explain the negative result. Besides that, non-PV foci seem to be distributed in different locations around both atria, not much in LAPW. Only 0.13% PAF patients could be triggered by non-PV foci located on the LAPW[37].While the IMPPROVE-PAF Trial[18]concluded that, PWI appears to be associated with greater freedom from recurrent atrial arrhythmias and AF in PAF patients, which conducted with cryoballoon ablation for a long-term follow-up. They emphasized that recurrences of atrial arrhythmia in patients with PAF seem to be lower and more asymptomatic in incidence than in persistent AF after catheter ablation, which might be used to explained why results were different from Bisignani et al. Actually, Mohanty et al revealed that the mechanism of late AF recurrence in patients with PAF following successful PVI was almost PV-independent and more reasons attributed to extra-PV triggers[38]. Thus, the understandings towards the efficacy of adjunctive PWI to PAF patients remain poorly understood and controversial. More studies regarding larger sample sizes, longer follow-up durations, or more sensitive or vigorous monitoring equipment may be needed.

Not only our meta-analysis results but also recent studies and meta-analyses gradually confirmed the value of the addition of PWI to PVI alone on improving the clinical outcomes of persistent AF patients, though CAPLA study did not support the empirical deployment of PWI for first-time AF ablation[11]. However, Kistler et al. mentioned that approach to rhythm monitoring after ablation, especially implantable devices for surveillance, was important and ideal. Meanwhile, it was needed to identify patient subgroups who may benefit better from adjunctive PWI[11]. Multivariable regression analysis from one large secondary analysis[33] demonstrated that patients with relatively older age, larger LADs, and persistent AF were significantly correlated with the efficacy of adjunctive PWI in reducing the arrhythmia recurrence, which can to some extent indicate how to choose proper patients to conduct adjunctive PWI regarding AF as a progressive and age-related diseases

Role of adjunctive PWI in cryoballoon and radiofrequency catheter

According to the present meta-analysis, when using CBA, the combination of PVI and PWI resulted in a lower recurrence of AF and AA than that in RFA group. Interestingly, adjunctive PWI slightly increased the recurrence of AFL/AT in RFA group when compared with PVI only. For adverse events, no significant difference was found between the two groups in sub-analyses.

Regarding to the results mentioned above, the PWI ablated by CBA seemed to reduce the recurrence of AF or AA more effectively than RFA. It might be explained by the theory that ablation lesions created by cryoballoon are always large and durable compared with those by radiofrequency catheter[39]. The CONVERGE trial also showing improved effectiveness with the novel epicardial-endocardial ablation approach compared to endocardial catheter ablation and the importance of the creation of durable lesions inside LAPW[40]. Two RCT trials conducting CBA for adjunctive PWI were enrolled in our analysis[9, 10]. Ahn et al, the first RCT to confirm the efficacy and safety of adjunctive PWI using CBA alone without additional RFCA in patients with persistent AF, stated that PWI could be achieved by delivering direct cryoenergy on the entire LAPW when using CBA, so that the isolation of arrhythmogenic substrate, for example ganglionated plexi, could be conducted efficiently. In contrast, Using RFCA to achieve PWI must conduct the roof and inferior linear ablations. Therefore, it could be explained why the benefit of PWI was deficient among studies using RFCA[9].

Particularly worth mentioning, in RFCA subgroup, adjunctive PWI slightly increased the recurrence of AFL/AT, which affected the efficacy of PWI on the recurrence of AA to a certain extent. Same to the results of our analysis, Sutter et al included in the present meta-analysis[41] and another study by Yokokawa et al both noted an increased incidence of AFL/AT after PVI + PWI[42]. Isolating a larger area of the atrium may create substrate for a macro-reentrant pathway leading to atrial flutter, and preventing recurrence of AF may allow maintenance of stable focal AT. This may explain the increase of recurrence of AT/AFL with PVI + PWI, especially when the incomplete linear block in PWI happened using the point-by-point fashion in RFCA[41, 43].

However, durable PWI usually means longer procedure time or high-power output, which may arose concerns about the increase in the risk of adverse events related with procedures like phrenic nerve injury or even esophageal damage. Though results from our meta-analysis and recent RCT trials did not show significant difference in the aspect of the incidence of adverse events when considering using the CBA method. Meanwhile, the results supported that the use of CBA in PWI could reduce the recurrence of AF/AA in AF patients. But it is still hard to conclude that CBA is prior to RFCA. Previous trials revealed that CBA was not suitable in all types of patients, particularly in patients with LA diameter exceeding 48 mm, and extra RFA was often required achieve PWI[10, 44]. More RCT trials are needed in the future.

Procedural adverse events related to adjunctive PWI.

Our meta-analysis did not show an increased risk of adverse events related to procedures regarding to PWI compared with PVI alone, no matter in safety endpoint analysis or in subgroup analyses. Atrio-esophageal fistula (AEF) is still the rare but serious and often fatal complication related to AF ablation procedures, especially in RFA. A nationwide survey conducted by Gandjbakhch et al reported that the estimated incidence rate may be 25 for 100 000 procedures, All cases of AEF occurred after RF ablation, no case was reported after cryoablation, 63% were seen persistent AF, and 37% of them underwent additional roof or more posterior linear ablation after PVI[45]. The recent meta-analysis revealed that adjunctive PWI was associated with significantly longer ablation time and total procedural time, but was not related to an extra increase of risk of procedure complication when a careful ablation protocol was followed[33]. With the rapid development of ablation technology and strategy, the balance between safety and efficacy should be carefully taken into consideration. Further studies, like PIVoTAL-IDE, STARAF3, LEAP-AF and HOT which are currently under way, are needed to verify to further shed light and elucidate these issues.

Limitations

Several limitations in our analysis must be taken into considerations. Firstly, more than half of studies enrolled in the present analysis are not randomized trials, thus the results are driven predominantly from retrospective analyses and non-randomized studies, which can lead to bias to some extent. Then, the included studies adopted different ablation techniques to achieve PWI. Heterogeneities among operators and centers may contribute to another bias. Though our results at last reported the importance of PWI in AF ablation whether in CBA or RFCA, more RCT trials with comparable levels of operators and definite ablation protocols are needed. Moreover, the methods to monitor arrhythmic events were diverse and heterogenous among the included studies. Part of them simply used electrocardiograph during every follow-up visit, while some others recorded the arrhythmia using long-time Holter, or even implantable devices, which might leave an inestimable influence on the results. Finally, follow-up periods, which ranged from 6 months to more than 3 years, were significant different in trials included. Aryana et al mentioned that positive results with PWI at 39 ± 9 months of follow-up, while there were no meaningful differences at 12 months[18].

We conducted a systematical review and meta-analysis to reveal a comprehensive understanding of the efficiency and safety of adjunctive PWI among AF patients. In brief, patients with AF who are undergoing AF ablation, additional PWI to PVI was associated with decreased recurrence of AF and atrial arrhythmias compared with PVI alone without an increased risk of AFL or AT, especially in patients with persistent AF and patients undergoing ablation with cryoballoon. It's worth noting that adjunctive PWI with radiofrequency ablation may induce a slight increase of recurrent AFL/AT compared with PVI only. More standardized randomized trials with long term follow up are needed to further explore the clinical benefits of the addition of PWI to PVI in AF patients.

Conflict of interests

The authors declare that there are no conflict of interests.

Abbreviations

AF, Atrial fibrillation; PAF, paroxysmal atrial fibrillation; PerAF, persistent atrial fibrillation; LAPWI, left atrium posterior wall isolation; PWI, Posterior wall isolation PVI Pulmonary vein isolation; AT, Atrial tachycardia; AFL, Atrial flutter; CBA, cryoballoon ablation; RFA, radiofrequency ablation.

Acknowledgments

We acknowledge the contribution of all participants and staff during this work. We also thank Siyuan Li for her help in polishing the manuscript.

Author Contributions

All authors contributed to the writing and editing of the manuscript. Ping Zhang, Lianfeng Liu and Yu Geng conceived and designed the project; Lianfeng Liu and Yu Geng were responsible for the statistical analysis and for writing the report. Ping Zhang is the correspondent author of this report. All authors contributed to the acquisition, analysis, and interpretation of data. Lianfeng Liu and Yu Geng drafted the manuscript. Lianfeng Liu and Yu Geng contributed equally to this work and should be considered as co-first authors.

Funding

This work was supported by Beijing Municipal Administration of Hospitals’ Ascent Plan (Grant No. DFL20190902), Tsinghua University Spring Breeze Fund (Grant No. 100003001), Beijing Municipal Science & Technology Commission (Granted number: Z191100006619007) and the Beijing Tsinghua Changgung Hospital Fund (Grant No. 12023C1002).

Availability of data and materials

The data presented in this study are available on request to the corresponding author ([email protected]) for purposes of reproducing the results or replicating the procedure. The data are not publicly available due to privacy restrictions.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Author details

¹Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.

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No competing interests reported.

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The Value of Adjunctive Left Atrial Posterior Wall Isolation on Clinical Outcomes in Atrial Fibrillation Patients: a systematic review and meta-analysis

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Abstract

Figures

Introduction

Methods

Search strategy and data extraction

Outcomes

Statistical analysis

Subgroup and Sensitivity Analyses

Results

Clinical outcomes

Subgroup analysis

Sensitivity analysis

Risk of bias and quality assessment of outcomes

Discussion

Role of the Left Atrial Posterior Wall in Atrial Fibrillation

Role of adjunctive PWI in paroxysmal and persistent AF

Role of adjunctive PWI in cryoballoon and radiofrequency catheter

Limitations

Conclusions

Declarations

References

Additional Declarations

Supplementary Files

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