Hybrid convergent ablation versus endocardial catheter ablation for atrial fibrillation: A systematic review and meta‐analysis

Abstract Introduction Endocardial catheter ablation (ECA) for atrial fibrillation (AF) has limited efficacy. Hybrid convergent procedure (HCP) with both epicardial and endocardial ablation is a novel strategy for AF treatment. In this meta‐analysis, we aimed to evaluate the efficacy and safety of HCP in AF ablation. Method We performed a comprehensive literature search for studies that evaluated the efficacy and safety of HCP compared with ECA for AF. The primary outcome was freedom of atrial arrhythmia (AA). The secondary outcome was the periprocedural complication rate. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were calculated using the random effects model. Results A total of eight studies, including 797 AF patients (mean age: 60.7 ± 9.8 years, 366 patients with HCP vs. 431 patients with ECA alone), were included. HCP showed a higher rate of freedom of AA compared with ECA (RR: 1.48, 95% CI: 1.13–1.94, p = .004). However, HCP was associated with higher rates of periprocedural complications (RR: 3.64, 95% CI: 2.06–6.43; p = .00001). Moreover, the HCP had a longer procedure time and postprocedural hospital stay. Conclusions Although hybrid ablation was associated with a higher success rate, this should be judged for increased periprocedural adverse events and extended hospital stay. Prospective large‐scale randomized trials are needed to validate these results.


| INTRODUC TI ON
Atrial fibrillation (AF) is the most common arrhythmia and continues to be a worldwide health burden. 1 The prevalence of AF in the United States is rising, with 12.1 million people are expected to have AF by 2030. 1 Conventional endocardial catheter ablation (ECA) is the mainstay interventional treatment modality of AF and targets mostly pulmonary veins (PVs) isolation. 2 However, the success rate of ECA is still unsatisfactory, with only half of the patients attaining freedom from atrial tachyarrhythmias at 1-year follow-up. 2 Furthermore, the creation of endocardial transmural lines during the procedure possesses a possible risk of esophageal, lung, and phrenic nerve injury. 3 Since its advent in the late 1980s, epicardial ablation for AF with various surgical approaches has continued to evolve. 4 The relative safety varies with the different techniques used, with comparable success rates to the ECA approach. 4 Hybrid convergent procedure (HCP), which combines both epicardial and endocardial ablation approaches, has emerged to utilize the advantages of both approaches. During the last decade, HCP has gained increasing acceptance in clinical practice, with several reports of durable antiarrhythmic outcomes. 5 However, studies analyzing the clinical outcomes of HCP are currently limited by small sample sizes. Therefore, we conducted this metaanalysis to evaluate all the available evidence to better assess the efficacy and safety of the hybrid convergent ablation HCP for atrial fibrillation.

| Data sources and search strategy
We performed a comprehensive search for published studies indexed in PubMed/MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to March 30, 2021. We also performed a manual search for additional relevant studies using references of the included articles. The following search terms were used: ("atrial fibrillation" or "AF"), ("hybrid" or "convergent" or "surgical-transcatheter" or "thoracoscopic-transcatheter" or "epicardial"), and ("endocardial ablation" or "catheter ablation" or "radiofrequency ablation"). The search was not limited by language, study design, or country of origin. Table S1 describes the full search term used in each database searched.

| Study selection
We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines to screen the studies. 6,7 We included full texts and abstracts of randomized controlled trials, cohort studies, and case-control studies. We excluded single-arm studies, animal studies, case reports, case series, reviews, editorials, and letters to editors. Two investigators (MM and AB) independently screened and selected the studies for the final review. Discrepancies were resolved by a third investigator (AA).

| Data extraction
We extracted the following data from the final studies: the last name of the first author, publication year, study design, country of origin, follow-up duration, sample size, efficacy endpoints (the freedom of atrial arrhythmia by the time of the last follow-up),

| Outcomes
The primary outcome of our meta-analysis was freedom of atrial arrhythmia (AA) by the time of the last follow-up. Total AA is defined as a composite of AF, sustained atrial tachycardia (AT), and atypical atrial flutter (AFL) after the index procedure.
Our secondary outcome was the rate of periprocedural complications through 30 days of the index procedure. Complications include the development of stroke, bleeding events that required intervention, pericardial effusion, cardiac tamponade, atrio-esophageal fistula, infections, phrenic nerve paralysis, and death.

| Statistical analysis
The meta-analysis was performed using Review Manager 5.3 (Cochrane Collaboration, Copenhagen, The Nordic Cochrane Centre). The random effects model was used to calculate the weighted pooled risk ratio (RR) and corresponding 95% confidence intervals (CI). We performed a subgroup analysis for the primary outcome based on the timing of HCP and the use of antiarrhythmic medications. We also performed a subgroup analysis for the safety outcome based on the surgical access used in the HCP. A p value of <.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I 2 index, where I 2 values >50% implied the presence of substantial heterogeneity. 8

| Quality assessment
We assessed the quality of the included studies using the Newcastle-Ottawa Scale for observational studies and the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for RCTs. 9,10 Two authors (MM and OS) independently assessed each study for bias.
Discrepancies were resolved by consensus. We did not evaluate for publication bias in our study because of the limited number of included studies. 11

| Study selection
A total of 667 studies were retrieved by our search strategy. Among these, 72 were eligible for the systematic review. Subsequently, we excluded 64 studies that were not relevant, had insufficient data, single-arm studies, or being a prognostic study. Finally, eight studies met our inclusion criteria and were included in the meta-analysis. 12-19 Figure 1 shows the PRISMA flow chart that illustrates how the final studies were selected. Table 1 shows the characteristics of the eight studies that were included in our meta-analysis. The studies included a total of 797 AF patients, of whom 366 underwent HCP and 431 underwent ECA.

| Study characteristics
The studies were published between 2011 and 2020. Based on the country of origin, four studies originated from the United States, one from South Korea, one from Slovenia, one from the United Kingdom, and one multicentric from the United States and the United Kingdom.
Based on study design, three studies were randomized controlled trials, four were retrospective cohorts, and one was a prospective cohort. All the included studies were full-text publications. The mean age was 60.7 ± 9.8 years, and males represented 77.4% of total patients. Around 93% of the entire study population had Per-LSPer AF, 27% treated previously with amiodarone, and 18.7% underwent prior ablation for AF. Table 2 summarizes the baseline comorbidities and preprocedural characteristics, including LVEF, LA diameter, and CHA2DS2-VASc score.

F I G U R E 1 PRISMA flow diagram for the selection of studies
All studies defined AF recurrence as any atrial arrhythmia lasting more than 30 s after the 3-month blanking period. Follow-up duration ranged from 16 to 30.5 months.

| Procedural characteristics
Five studies performed HCP via transdiaphragmatic subxiphoid incision, two via thoracoscopy, and one via mini-thoracotomy approach. Three studies performed staged HCP, whereas the rest conducted concomitant endocardial and epicardial HCP. The detailed ablation lesion sets, and sequence of each study were summarized in Table S2. The assessment of success rates of HCP and ECA was made mainly through Holter monitoring ranging from 24 h to 7 days.
Only two studies utilized implantable loop recorder monitoring, 16,17 and one study interrogated the pacemaker devices when available. 18

| Primary outcomes
All the included studies reported the rate of freedom of atrial arrhythmia by the time of the last follow-up (average of 24 months).
HCP showed a higher rate of freedom of AA compared with ECA (RR: 1.48, 95% CI: 1.13-1.94, p = .004). However, significant heterogeneity was found (I 2 = 77%, p < .0001) (Figure 2). A sensitivity analysis was conducted by removing one study at a time to reduce heterogeneity and found no significant change in our results Abbreviations: AA, atrial arrythmia (AF, Atrial flutter, or atrial tachycardia); AAD, antiarrhythmic medications; AF, atrial fibrillation; LA, left atrium; LAD, left atrium diameter; LSP, long standing persistent.

TA B L E 1 Characteristics of studies included in the meta-analysis
( Figure S1). Furthermore, subgroup analysis based on the HCP surgical access failed to improve the observed heterogeneity.

| Secondary outcomes
The rate of periprocedural complications was higher in the HCP

| Quality assessment
We assessed the quality of the included studies by using the

Newcastle-Ottawa Scale for cohort studies and the Revised
Cochrane risk-of-bias tool for randomized controlled trials, as shown in Tables S3 and S4. All studies scored low to moderate in quality assessment.

| DISCUSS ION
This study was a systematic review and meta-analysis of all studies investigating the efficacy and safety of the hybrid convergent procedure compared to the conventional endocardial catheter ablation for atrial fibrillation. Our meta-analysis demonstrated that the HCP significantly improved the freedom of atrial tachyarrhythmia.
However, it was associated with higher perioperative complications, but HCP through thoracoscopy access showed a better safety profile. Furthermore, HCP was associated with longer procedure time and hospital stay.
Following conventional endocardial ablation, the recurrence rate of AF varies significantly among different studies; early recurrences (within the first 3 months) occur in almost half of the patients after ECA. 20 Late recurrence (after 3 months) was observed in more than 40% of patients as detected by continuous rhythm monitoring in the CIRCA-DOSE trial. 2 Thus, repeated procedures and the use of maintenance antiarrhythmic medications are usually necessary to achieve acceptable success rates. 21 The rate of repeated ablation procedures may reach up to 80%. 22 Despite added strategies beyond PV isolation, the success rate did not remarkably improve. In our study, the rate of late AA recurrence for the ECA group was significantly higher than HCP (51.86% vs. 29.25%, respectively). The enhanced success risk of HCP could be explained by additional ablation of arrhythmogenic targets beyond the isolation of pulmonary veins and robust lesion formation through direct epicardial-catheter contact. 25 However, the ECA strategy showed a better safety profile than the HCP. Our results showed that the procedural-related However, there are several strengths to our meta-analysis. First, to our knowledge, this is the first meta-analysis to include eight studies with three RCTs to compare the clinical outcomes of adjunctive epicardial strategy with conventional ECA strategy in terms of efficacy and safety. Second, we performed a subgroup analysis for the late atrial arrhythmia recurrence rate based on the timing of the HCP and the use of AADs. In addition, no heterogeneity was found in the measurement of our safety outcome.
In conclusion, our meta-analysis demonstrated that the hybrid convergent procedure for AF ablation was associated with a higher success rate and reduced the risk of late atrial arrhythmia recurrence. However, this should be judged for increased periprocedural adverse events and extended hospital stay. Prospective large-scale randomized trials are needed to validate these results.

CO N FLI C T O F I NTE R E S T
The authors declared no conflict of interest.

I R B A PPROVA L
This study was deemed exempt by the Institutional Review Board of the University of Toledo, as it was a meta-analysis of published studies that included de-identified patient information.