# Biatrial versus Isolated Left Atrial Ablation in Atrial Fibrillation: A Systematic Review and Meta-Analysis

Authors: Hongmu Li; Xifeng Lin; Xun Ma; Jun Tao; Rongjun Zou; Songran Yang; Haibo Liu; Ping Hua
Journal: BioMed Research International
 (2018)

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## Abstract

Objective. The outcomes of biatrial ablation (BA) and isolated left atrial ablation (LA) in atrial fibrillation remain inconclusive. In this meta-analysis, we assess the currently available evidence to compare outcomes between BA and LA.Methods. Electronic searches were performed from database inception to December 2016, and relevant studies were accessed. Odds ratios and weight mean differences with 95% confidence intervals are reported. Twenty-one studies comprising 3609 patients were included in the present meta-analysis.Results. The prevalence of sinus rhythm in the BA cohort was similar to that in the LA cohort at discharge, at 12 months, and after more than 1 year of follow-up. However, at 6 months, the prevalence of sinus rhythm was higher in the BA cohort than in the LA cohort. The rate of permanent pacemaker implantation was higher in the BA cohort than in the LA cohort. However, 30-day and late mortality and neurological events were similar between the BA and LA groups.Conclusion. There was no significant difference in the rate of restored sinus rhythm, the risk of death, and cerebrovascular events between BA and LA, but BA had a higher rate of permanent pacemaker implantation.


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## Body

## 1. Introduction

Atrial fibrillation (AF) is a major healthcare problem worldwide which has enormous economic and public health implications. AF is associated with an increased risk of stroke, heart failure, and all-cause mortality [1–3].Surgical ablation was introduced as a treatment option by Cox et al. [4] in 1991, and it is currently an effective curative strategy for AF. Haïssaguerre et al. [5] suggested that ectopic beats from pulmonary veins may cause AF, and the field of pulmonary vein isolation (PVI) was consequently established and is now performed via catheter or surgical ablation [6]. Left ablation (LA) has historically been the main method used to treat AF, and it has a fairly good clinical effect [7, 8]. However, some studies have suggested that LA is less efficacious than biatrial ablation (BA), especially when a right-side AF trigger is present [9]. Hence, because outcomes have been inconclusive, Phan et al. [10] and Zheng et al. [11] reported relevant meta-analyses in 2014, but they arrived at a different conclusion. The authors showed that BA was more effective than LA and that the rate of permanent pacemaker implantation was also higher in the BA cohort than in the LA cohort. However, Zheng et al. [11] suggested that the effects of BA and LA are the same.In the past two years, several other studies [8, 12–15] have compared BA and LA in AF, with controversial outcomes. Hence, in this meta-analysis, we sought to assess the current evidence available on this issue.


## 2. Methods

### 2.1. Literature Search Strategy

Electronic searches were performed in August 2016 without search restrictions. The primary sources were the electronic Medline, PubMed, Cochrane Library, and EMBASE databases, which were searched from their date of inception to August 2016. The following search terms were used: “maze,” “biatrial,” “bi-atrial,” “uniatrial,” “left atrial,” and “ablation.” When duplicate published trials with accumulating numbers of patients or increased lengths of follow-up were encountered, the most recent or most complete report was considered. All titles and abstracts identified in the electronic search were uploaded into an EndNote (version X7; Thomson Corporation, Stanford, USA) database (Figure1).Figure 1
Selection of studies for the meta-analysis.


### 2.2. Inclusion and Exclusion Criteria

All available randomized, controlled trials (RCTs) and retrospective comparative studies that compared BA with LA in all age groups were included. Abstracts, case reports, conference presentations, editorials, reviews, and expert opinions were excluded. When institutions published duplicate studies with accumulating numbers of patients or increased lengths of follow-up, only the most complete report was included. Reference lists were also manually searched for further relevant studies.


### 2.3. Data Extraction and Critical Appraisal

Two reviewers (Hongmu Li and Xifeng Lin) conducted data extraction independent of the included studies. Data on authorship, year of publication, study design, study population, baseline characteristics, characteristics related to outcomes, and duration of follow-up were extracted from each study. Reported percentages were approximated to numbers. The risk of bias was assessed using the Downs and Black checklist [16] for randomized and observational studies. Discrepancies between the reviewers were resolved by discussion until consensus was reached. The final results were reviewed by the senior investigator (Ping Hua).


### 2.4. Quality Assessment and Statistical Analysis

The included studies were rated to determine the level of quality of the provided evidence according to the criteria of the Centre for Evidence-Based Medicine in Oxford, UK [17]. The methodological quality of the RCTs was assessed with the Cochrane risk of bias tool [18]. The methodological quality of retrospective studies was assessed with the modified Newcastle-Ottawa scale [19, 20].This meta-analysis was performed using Review Manager Version 5.3 (Cochrane Collaboration, Oxford, UK). Dichotomous variables from individual studies were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs).Q-statistics (P<0.10) orI2 statistics were performed to test for heterogeneity between included studies, and values of 50% or higher were considered to be indicative of substantial heterogeneity. If there was substantial heterogeneity, the possible clinical and methodological reasons for this were explored qualitatively. Publication bias was examined through a visual inspection of funnel plots and assessed by applying Egger’s weighted regression statistic and considering a P value less than 0.05 as indicating significant publication bias. A P value of less than 0.05 was considered statistically significant for all analyses.


### 2.5. Synthesis of Evidence

Our electronic literature search resulted in the retrieval of 398 citations. Of these, 372 were excluded after duplicate and irrelevant references were excluded, and 49 potentially relevant articles were retrieved. Finally, following a manual search of reference lists and a critical appraisal, 21 studies comprising 3609 patients were included in this meta-analysis. Two articles had redundant publications but covered different characteristics [21, 22].


### 2.6. Quality Assessment and Baseline Characteristics of Eligible Studies

In all, 21 studies were included in this meta-analysis, including three prospective randomized trials [23–25], five prospective observational studies [13, 26–29], and 13 retrospective observational studies [8, 12, 14, 15, 21, 22, 30–36]. The risk of bias in each study is shown in Figure 2 and Table 1. Among the 3609 patients, 1901 received BA, and 1708 received LA. Patients in the BA group underwent a classical or modified maze procedure, including both left-sided and right-sided maze procedures. However, patients in the LA group underwent a left-sided maze procedure that included PVI, left atrial posterior wall isolation, mitral isthmus ablation, and left atrial appendage excision.Table 1
Risk of bias in observational studies.
Study Selection Comparability Outcome Quality score Assignment for treatment Representative treatment group Representative reference group Comparable for 1, 2, 3,4 Comparable for 5, 6, 7,8 Assessment of outcome Adequate follow-up Gualis et al. 2016 No Yes Yes 1, 2 5, 8 Yes No ★★★★★ Liu et al., 2015 No Yes Yes 1, 2 5, 8 No Yes ★★★★★ Henn et al., 2015 No Yes Yes NR 5, 6 Yes No ★★★★ Pecha et al., 2014 No Yes Yes 1, 2 5, 8 Yes NR ★★★★★ Jiang, 2014 No Yes Yes 1, 2 8 Yes No ★★★★ Soni et al., 2013 No Yes Yes 1, 2 8 No No ★★★ Pecha et al., 2014 No Yes Yes 1, 2 5, 6 Yes Yes ★★★★★★ Onorati et al., 2011 No Yes Yes 1, 2 5, 6, 8 Yes Yes ★★★★★★★ Kim et al., 2011 No Yes Yes 1, 2 7, 8 Yes No ★★★★★ Breda et al., 2011 No Yes Yes 1, 2 6, 8 No No ★★★★ Albage et al., 2011 No Yes Yes 1, 2 7 Yes No ★★★★ McCarthy et al., 2010 No Yes Yes 1, 2 8 Yes Yes ★★★★★★ Deneke et al., 2009 No Yes Yes 1, 4 6, 8 Yes Yes ★★★★★★ Geuzebroek et al., 2008 No Yes Yes 1, 2 5 No Yes ★★★★ Deneke et al., 2007 No Yes Yes 1, 4 8 Yes Yes ★★★★★ Ryan et al., 2004 No Yes Yes NR 5, 6, 7, 8 Yes No ★★★★★ Guden et al., 2003 No Yes Yes 1, 2, 3 NR Yes Yes ★★★★★ Takami et al., 1999 No Yes Yes 1, 2, 3 5, 7, 8 Yes Yes ★★★★★★★ NR: no report; comparability variables: 1 = age; 2 = gender; 3 = body mass index; 4 = type of AF; 5 = Euro score; 6 = preoperative antiarrhythmic drugs; 7 = anatomic complexity (more than one artery and/or vein); 8 = single surgeon.Figure 2
Risk of bias in RCT studies.Three studies used cryoablation energy [15, 27, 31], eleven studies used radiofrequency energy [12–14, 21, 23, 25, 26, 29, 32–34], and the remaining studies used a combination of different energy sources, including radiofrequency, cryoablation, and microwave and “cut-and-sew” [8, 22, 24, 28, 30, 35, 36]. Concomitant coronary artery bypass grafting surgery was reported in 10 studies [8, 13, 21, 22, 25, 27–31, 36], while a concomitant valvular operation was performed in other included studies. The baseline characteristics of the patients in the included studies are shown in Tables 2 and 3.Table 2
Characteristics of the studies that were initially included in the meta-analysis.
First author Year Country Study period Type of study Follow-up (MO) n  (BA) n  (LA) Type of ablation Lesion set Cardiac operation Gualis 2016 Spain 2006–2011 R 36 67 83 CY PVI, LAA, RAA, TC, CS, WG AVR AVP MVR MVP TVP  Liu 2015 China 2012-2012 R 3–12R 86 111 RF PVI, LAA, RAA MVR DVR TVP  Henn 2015 USA 2002–2014 P, non-RCT 5 years 532 44 RF PVI, LAA, RAA, TC, CS, WG AVR CABG MVR MVP TVP  Pecha 2014 Germany 2008–2011 R 12 66 66 RF, CY LVI, LAA, CI, RAA, TC CABG AVR MVR TVR  Jiang 2014 China 2008–2012 R NR 61 48 RF PVI, MV, LAA, RAA, TC, CS, WG MVR MVP TVP  Soni 2013 USA 2007–2011 R 12 91 214 RF, CY, MW PVI, PW, MI, LAA MM AVR MVR CABG MVP TVP  Pecha 2014 Germany 2003–2012 R 30 days 131 463 CY, RF LVI, LAA, BLI, CI, RAA, TC AVR AVP MVR MVP TVP CABG ASD VSD  Onorati 2011 Italy 2003–2008 P, non-RCT 15 109 32 RF PVI MV LAA RAA TC CS WG AVR AVP MVR MVP TVP  Kim 2011 South Korea 2006–2009 R 26 ± 13.3 199 82 CY PVI, PW, MI, LAA, MM, CS AVR AVP MVR MVP TVP CABG ASD VSD  Breda 2011 Brazil 2003–2009 R 12.16 ± 10.89 15 15 RF PVI, PW, MI, LAA, MM MVR MVP  Albage 2011 Sweden 2005–2010 P, non-RCT 1–12R 44 71 CY PVI, PW, MI, LAA, Maze III AVR CABG MVP TVP MVR ASD MVP  McCarthy 2010 USA 2004–2008 P, non-RCT 5–24R 91 75 RF, CY, cut-and-sew PVI LAA RAA TC AVR MVR TVP CABG  Deneke 2009 Germany NR R 55 ± 17 64 66 RF PVI, PW, MI, LAA, Maze III MVR, AVR, CABG  Wang 2009 China 2004–2007 P, RCT 28 ± 5 150 149 RF PVI, PW, MI, LAA, CTI, MM MVR AVR MVP TVR TVP AVP  Srivastava 2008 India NR P, RCT 44 40 40 RF, CY PVI, PW, MI, LAA, Maze III MVR AVR MVP TVR TVP AVP  Geuzebroek 2008 Netherlands 1999–2005 R NR 26 40 RF PVI, PW, MI, LAA, Maze III MVR AVR MVP TVR TVP AVP  Deneke 2007 Germany 1997–2005 R 21 106 116 RF PVI MV LAA RAA, MM MVR MVP CABG AVR  Calo 2006 Italy NR P, RCT 15 ± 5 (BA)/13 ± 6 (LA) 39 41 RF PVI MV LAA RAA TC CS WG NR  Ryan 2004 USA 1996–2003 R 595 ± 750 days 36 7 RF, CY, cut-and-sew PVI, PW, MI, LAA, Maze III NR  Guden 2003 Turkey 2001 P, non-RCT 10.9 ± 5.58 48 57 RF PVI, PW, MI, LAA, Maze III AVR CABG MVP TVP MVR ASD MVP  Takami 1999 Japan NR R 34.1 ± 11.3 (BA)/17.8 ± 3.8 (LA) 30 20 CY, cut-and-sew PVI, PW, MI, LAA, CTI, Maze III MVR, CABG, AVR, TVR MO: month; R: range; P: p retrospective observational; RCT: randomized, controlled trial; BA: biatrial ablation; LA: left atrial ablation; CY: cryoablation; RF: radiofrequency ablation; MW: microwave ablation; PVI: pulmonary vein isolation; LAA: left atrial appendage; RAA: right atrial appendage; TC: terminal crest; CS: coronary sinus; WG: Waterston’s groove; MI: mitral isthmus; MM: modified maze; CI: cavotricuspid isthmus; PW: posterior wall; AVR: aortic valve replacement; AVP: aortic valvuloplasty; MVR: mitral valve replacement; MVP: mitral valvuloplasty; TVP: tricuspid valvuloplasty; CABG: coronary artery bypass grafting; ASD: atrial septal defect repair; VSD: ventricular septal defect repair; NR: no report.Table 3
Baseline characteristics of the included studies.
First author Age (BA/LA, years) Male (BA/LA) Diabetes (BA/LA) Heart failure (BA/LA) Cerebrovascular events (BA/LA) Hypertension (BA/LA) Type of AF Gualis 65.1 ± 10.2/71.6 ± 6.8 29/39 15/17 32/31 7/12 NR Permanent persistent Liu 49.87 ± 8.96/47.98 ± 8.64 21/23 NR NR NR NR Permanent persistent Henn 64 ± 12 NR NR NR NR NR Permanent persistent Pecha 70.5 ± 7.3/70.1 ± 7.5 45/40 16/13 NR NR NR Paroxysmal persistent permanent Jiang 52.7 ± 4.9/50.7 ± 5.9 22/21 7/8 36/29 2/2 11/8 Paroxysmal persistent permanent Soni NR NR NR NR NR NR Paroxysmal persistent permanent Pecha 59 ± 28/68 ± 12 54/116 16/40 NR NR 67/118 Paroxysmal persistent permanent Onorati 64 ± 9/65 ± 8 79/18 40/10 NR NR 37/15 Permanent persistent Kim 56.3 ± 12.0/52.1 ± 11.9 75/47 19/5 NR NR 32/21 Paroxysmal persistent permanent Breda 60.0 ± 8.07/46.3 ± 9.54 9/5 NR 10/6. NR NR Permanent persistent Albage 64.9 ± 10.4/66.9 ± 6.7 34/54 4/11 17/28 2/7 10/27 Paroxysmal persistent permanent McCarthy 68.7 ± 10.3/66.8 ± 12.1 42/88 13/22 NR NR NR Paroxysmal persistent permanent Wang 67 ± 8/69 ± 9 NR NR NR NR NR Permanent persistent Deneke 53.4 ± 10.8/54.2 ± 10.1 54/62 NR NR NR NR Permanent persistent Srivastava 37.11 ± 11.12/36.03 ± 7.99 19/22 NR NR NR NR Permanent persistent Geuzebroek 63.3 ± 7.9/61.1 ± 10.3 21/17 NR NR NR NR Paroxysmal persistent permanent Deneke 68 ± 9 NR NR NR NN NR Paroxysmal persistent permanent Calo 57.9 ± 8.9/59.2 ± 9.1 26/26 NR NR NR 16/18 Paroxysmal persistent permanent Ryan NR NR NR NR NR NR Paroxysmal persistent permanent Guden 52 ± 11/54 ± 9 14/23 NR NR N NR Permanent persistent Takami 54.7 ± 8.8/58.3 ± 8.7 11/9 NR NR NR NR Paroxysmal persistent permanent BA: biatrial ablation; LA: left atrial ablation; NR: no report.


## 2.1. Literature Search Strategy

Electronic searches were performed in August 2016 without search restrictions. The primary sources were the electronic Medline, PubMed, Cochrane Library, and EMBASE databases, which were searched from their date of inception to August 2016. The following search terms were used: “maze,” “biatrial,” “bi-atrial,” “uniatrial,” “left atrial,” and “ablation.” When duplicate published trials with accumulating numbers of patients or increased lengths of follow-up were encountered, the most recent or most complete report was considered. All titles and abstracts identified in the electronic search were uploaded into an EndNote (version X7; Thomson Corporation, Stanford, USA) database (Figure1).Figure 1
Selection of studies for the meta-analysis.


## 2.2. Inclusion and Exclusion Criteria

All available randomized, controlled trials (RCTs) and retrospective comparative studies that compared BA with LA in all age groups were included. Abstracts, case reports, conference presentations, editorials, reviews, and expert opinions were excluded. When institutions published duplicate studies with accumulating numbers of patients or increased lengths of follow-up, only the most complete report was included. Reference lists were also manually searched for further relevant studies.


## 2.3. Data Extraction and Critical Appraisal

Two reviewers (Hongmu Li and Xifeng Lin) conducted data extraction independent of the included studies. Data on authorship, year of publication, study design, study population, baseline characteristics, characteristics related to outcomes, and duration of follow-up were extracted from each study. Reported percentages were approximated to numbers. The risk of bias was assessed using the Downs and Black checklist [16] for randomized and observational studies. Discrepancies between the reviewers were resolved by discussion until consensus was reached. The final results were reviewed by the senior investigator (Ping Hua).


## 2.4. Quality Assessment and Statistical Analysis

The included studies were rated to determine the level of quality of the provided evidence according to the criteria of the Centre for Evidence-Based Medicine in Oxford, UK [17]. The methodological quality of the RCTs was assessed with the Cochrane risk of bias tool [18]. The methodological quality of retrospective studies was assessed with the modified Newcastle-Ottawa scale [19, 20].This meta-analysis was performed using Review Manager Version 5.3 (Cochrane Collaboration, Oxford, UK). Dichotomous variables from individual studies were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs).Q-statistics (P<0.10) orI2 statistics were performed to test for heterogeneity between included studies, and values of 50% or higher were considered to be indicative of substantial heterogeneity. If there was substantial heterogeneity, the possible clinical and methodological reasons for this were explored qualitatively. Publication bias was examined through a visual inspection of funnel plots and assessed by applying Egger’s weighted regression statistic and considering a P value less than 0.05 as indicating significant publication bias. A P value of less than 0.05 was considered statistically significant for all analyses.


## 2.5. Synthesis of Evidence

Our electronic literature search resulted in the retrieval of 398 citations. Of these, 372 were excluded after duplicate and irrelevant references were excluded, and 49 potentially relevant articles were retrieved. Finally, following a manual search of reference lists and a critical appraisal, 21 studies comprising 3609 patients were included in this meta-analysis. Two articles had redundant publications but covered different characteristics [21, 22].


## 2.6. Quality Assessment and Baseline Characteristics of Eligible Studies

In all, 21 studies were included in this meta-analysis, including three prospective randomized trials [23–25], five prospective observational studies [13, 26–29], and 13 retrospective observational studies [8, 12, 14, 15, 21, 22, 30–36]. The risk of bias in each study is shown in Figure 2 and Table 1. Among the 3609 patients, 1901 received BA, and 1708 received LA. Patients in the BA group underwent a classical or modified maze procedure, including both left-sided and right-sided maze procedures. However, patients in the LA group underwent a left-sided maze procedure that included PVI, left atrial posterior wall isolation, mitral isthmus ablation, and left atrial appendage excision.Table 1
Risk of bias in observational studies.
Study Selection Comparability Outcome Quality score Assignment for treatment Representative treatment group Representative reference group Comparable for 1, 2, 3,4 Comparable for 5, 6, 7,8 Assessment of outcome Adequate follow-up Gualis et al. 2016 No Yes Yes 1, 2 5, 8 Yes No ★★★★★ Liu et al., 2015 No Yes Yes 1, 2 5, 8 No Yes ★★★★★ Henn et al., 2015 No Yes Yes NR 5, 6 Yes No ★★★★ Pecha et al., 2014 No Yes Yes 1, 2 5, 8 Yes NR ★★★★★ Jiang, 2014 No Yes Yes 1, 2 8 Yes No ★★★★ Soni et al., 2013 No Yes Yes 1, 2 8 No No ★★★ Pecha et al., 2014 No Yes Yes 1, 2 5, 6 Yes Yes ★★★★★★ Onorati et al., 2011 No Yes Yes 1, 2 5, 6, 8 Yes Yes ★★★★★★★ Kim et al., 2011 No Yes Yes 1, 2 7, 8 Yes No ★★★★★ Breda et al., 2011 No Yes Yes 1, 2 6, 8 No No ★★★★ Albage et al., 2011 No Yes Yes 1, 2 7 Yes No ★★★★ McCarthy et al., 2010 No Yes Yes 1, 2 8 Yes Yes ★★★★★★ Deneke et al., 2009 No Yes Yes 1, 4 6, 8 Yes Yes ★★★★★★ Geuzebroek et al., 2008 No Yes Yes 1, 2 5 No Yes ★★★★ Deneke et al., 2007 No Yes Yes 1, 4 8 Yes Yes ★★★★★ Ryan et al., 2004 No Yes Yes NR 5, 6, 7, 8 Yes No ★★★★★ Guden et al., 2003 No Yes Yes 1, 2, 3 NR Yes Yes ★★★★★ Takami et al., 1999 No Yes Yes 1, 2, 3 5, 7, 8 Yes Yes ★★★★★★★ NR: no report; comparability variables: 1 = age; 2 = gender; 3 = body mass index; 4 = type of AF; 5 = Euro score; 6 = preoperative antiarrhythmic drugs; 7 = anatomic complexity (more than one artery and/or vein); 8 = single surgeon.Figure 2
Risk of bias in RCT studies.Three studies used cryoablation energy [15, 27, 31], eleven studies used radiofrequency energy [12–14, 21, 23, 25, 26, 29, 32–34], and the remaining studies used a combination of different energy sources, including radiofrequency, cryoablation, and microwave and “cut-and-sew” [8, 22, 24, 28, 30, 35, 36]. Concomitant coronary artery bypass grafting surgery was reported in 10 studies [8, 13, 21, 22, 25, 27–31, 36], while a concomitant valvular operation was performed in other included studies. The baseline characteristics of the patients in the included studies are shown in Tables 2 and 3.Table 2
Characteristics of the studies that were initially included in the meta-analysis.
First author Year Country Study period Type of study Follow-up (MO) n  (BA) n  (LA) Type of ablation Lesion set Cardiac operation Gualis 2016 Spain 2006–2011 R 36 67 83 CY PVI, LAA, RAA, TC, CS, WG AVR AVP MVR MVP TVP  Liu 2015 China 2012-2012 R 3–12R 86 111 RF PVI, LAA, RAA MVR DVR TVP  Henn 2015 USA 2002–2014 P, non-RCT 5 years 532 44 RF PVI, LAA, RAA, TC, CS, WG AVR CABG MVR MVP TVP  Pecha 2014 Germany 2008–2011 R 12 66 66 RF, CY LVI, LAA, CI, RAA, TC CABG AVR MVR TVR  Jiang 2014 China 2008–2012 R NR 61 48 RF PVI, MV, LAA, RAA, TC, CS, WG MVR MVP TVP  Soni 2013 USA 2007–2011 R 12 91 214 RF, CY, MW PVI, PW, MI, LAA MM AVR MVR CABG MVP TVP  Pecha 2014 Germany 2003–2012 R 30 days 131 463 CY, RF LVI, LAA, BLI, CI, RAA, TC AVR AVP MVR MVP TVP CABG ASD VSD  Onorati 2011 Italy 2003–2008 P, non-RCT 15 109 32 RF PVI MV LAA RAA TC CS WG AVR AVP MVR MVP TVP  Kim 2011 South Korea 2006–2009 R 26 ± 13.3 199 82 CY PVI, PW, MI, LAA, MM, CS AVR AVP MVR MVP TVP CABG ASD VSD  Breda 2011 Brazil 2003–2009 R 12.16 ± 10.89 15 15 RF PVI, PW, MI, LAA, MM MVR MVP  Albage 2011 Sweden 2005–2010 P, non-RCT 1–12R 44 71 CY PVI, PW, MI, LAA, Maze III AVR CABG MVP TVP MVR ASD MVP  McCarthy 2010 USA 2004–2008 P, non-RCT 5–24R 91 75 RF, CY, cut-and-sew PVI LAA RAA TC AVR MVR TVP CABG  Deneke 2009 Germany NR R 55 ± 17 64 66 RF PVI, PW, MI, LAA, Maze III MVR, AVR, CABG  Wang 2009 China 2004–2007 P, RCT 28 ± 5 150 149 RF PVI, PW, MI, LAA, CTI, MM MVR AVR MVP TVR TVP AVP  Srivastava 2008 India NR P, RCT 44 40 40 RF, CY PVI, PW, MI, LAA, Maze III MVR AVR MVP TVR TVP AVP  Geuzebroek 2008 Netherlands 1999–2005 R NR 26 40 RF PVI, PW, MI, LAA, Maze III MVR AVR MVP TVR TVP AVP  Deneke 2007 Germany 1997–2005 R 21 106 116 RF PVI MV LAA RAA, MM MVR MVP CABG AVR  Calo 2006 Italy NR P, RCT 15 ± 5 (BA)/13 ± 6 (LA) 39 41 RF PVI MV LAA RAA TC CS WG NR  Ryan 2004 USA 1996–2003 R 595 ± 750 days 36 7 RF, CY, cut-and-sew PVI, PW, MI, LAA, Maze III NR  Guden 2003 Turkey 2001 P, non-RCT 10.9 ± 5.58 48 57 RF PVI, PW, MI, LAA, Maze III AVR CABG MVP TVP MVR ASD MVP  Takami 1999 Japan NR R 34.1 ± 11.3 (BA)/17.8 ± 3.8 (LA) 30 20 CY, cut-and-sew PVI, PW, MI, LAA, CTI, Maze III MVR, CABG, AVR, TVR MO: month; R: range; P: p retrospective observational; RCT: randomized, controlled trial; BA: biatrial ablation; LA: left atrial ablation; CY: cryoablation; RF: radiofrequency ablation; MW: microwave ablation; PVI: pulmonary vein isolation; LAA: left atrial appendage; RAA: right atrial appendage; TC: terminal crest; CS: coronary sinus; WG: Waterston’s groove; MI: mitral isthmus; MM: modified maze; CI: cavotricuspid isthmus; PW: posterior wall; AVR: aortic valve replacement; AVP: aortic valvuloplasty; MVR: mitral valve replacement; MVP: mitral valvuloplasty; TVP: tricuspid valvuloplasty; CABG: coronary artery bypass grafting; ASD: atrial septal defect repair; VSD: ventricular septal defect repair; NR: no report.Table 3
Baseline characteristics of the included studies.
First author Age (BA/LA, years) Male (BA/LA) Diabetes (BA/LA) Heart failure (BA/LA) Cerebrovascular events (BA/LA) Hypertension (BA/LA) Type of AF Gualis 65.1 ± 10.2/71.6 ± 6.8 29/39 15/17 32/31 7/12 NR Permanent persistent Liu 49.87 ± 8.96/47.98 ± 8.64 21/23 NR NR NR NR Permanent persistent Henn 64 ± 12 NR NR NR NR NR Permanent persistent Pecha 70.5 ± 7.3/70.1 ± 7.5 45/40 16/13 NR NR NR Paroxysmal persistent permanent Jiang 52.7 ± 4.9/50.7 ± 5.9 22/21 7/8 36/29 2/2 11/8 Paroxysmal persistent permanent Soni NR NR NR NR NR NR Paroxysmal persistent permanent Pecha 59 ± 28/68 ± 12 54/116 16/40 NR NR 67/118 Paroxysmal persistent permanent Onorati 64 ± 9/65 ± 8 79/18 40/10 NR NR 37/15 Permanent persistent Kim 56.3 ± 12.0/52.1 ± 11.9 75/47 19/5 NR NR 32/21 Paroxysmal persistent permanent Breda 60.0 ± 8.07/46.3 ± 9.54 9/5 NR 10/6. NR NR Permanent persistent Albage 64.9 ± 10.4/66.9 ± 6.7 34/54 4/11 17/28 2/7 10/27 Paroxysmal persistent permanent McCarthy 68.7 ± 10.3/66.8 ± 12.1 42/88 13/22 NR NR NR Paroxysmal persistent permanent Wang 67 ± 8/69 ± 9 NR NR NR NR NR Permanent persistent Deneke 53.4 ± 10.8/54.2 ± 10.1 54/62 NR NR NR NR Permanent persistent Srivastava 37.11 ± 11.12/36.03 ± 7.99 19/22 NR NR NR NR Permanent persistent Geuzebroek 63.3 ± 7.9/61.1 ± 10.3 21/17 NR NR NR NR Paroxysmal persistent permanent Deneke 68 ± 9 NR NR NR NN NR Paroxysmal persistent permanent Calo 57.9 ± 8.9/59.2 ± 9.1 26/26 NR NR NR 16/18 Paroxysmal persistent permanent Ryan NR NR NR NR NR NR Paroxysmal persistent permanent Guden 52 ± 11/54 ± 9 14/23 NR NR N NR Permanent persistent Takami 54.7 ± 8.8/58.3 ± 8.7 11/9 NR NR NR NR Paroxysmal persistent permanent BA: biatrial ablation; LA: left atrial ablation; NR: no report.


## 3. Outcomes

### 3.1. Assessment of Efficacy

The data were pooled from 16 studies [12–15, 21–26, 28, 29, 31–33, 36] that assessed the efficacy of restoring sinus rhythm (SR), and the results showed that there was no significant difference between the BA and LA groups at discharge (78.3% versus 73.86%; OR: 1.02; 95% CI: 0.69–1.51; P=0.92;I2 = 66%). However, the overall prevalence of SR was higher in the BA group than in the LA group at a 6-month follow-up (78.82% versus 69.67%; OR: 1.54; 95% CI: 1.17–2.03; P=0.002;I2 = 0%) [14, 15, 22, 24–26, 30–32, 36]. For patients with a follow-up at 12 months [8, 14, 15, 26, 27, 30, 31, 34] and after more than 1 year [12, 15, 23–25, 31], the prevalence of SR in the BA group was similar to that in the LA group (63.01% versus 65.47%; OR: 1.31; 95% CI: 0.70–2.48; P=0.40;I2 = 77%). The weighted average mean follow-up for studies reporting SR after more than 1 year was 23.3 months. These results are shown in Figure 3.Figure 3
Restored SR at discharge, 6 months, and 12 months and beyond 1 year.


### 3.2. Mortality and Major Complications

Eight studies with 1185 patients investigated mortality after the BA or LA procedure. When effects were pooled, there was no significant difference in either early mortality [8, 14, 23, 27–29, 33] (<30 days, OR: 1.02; 95% CI: 0.36–2.90; P=0.97;I2 = 31%, Figure 4) or late mortality [23, 27, 29, 31, 35] (OR: 2.31; 95% CI: 0.86–6.22; P=0.10;I2 = 0%, Figure 5) between the BA and LA groups.Figure 4
Mortality within 30 days.Figure 5
Late mortality.There was no significant increase in the risk of cerebrovascular events [8, 27, 28, 31] between the two groups (OR: 0.61; 95% CI: 0.16–2.40; P=0.48;I2 = 0%, Figure 6). In eight studies that compared LA with BA, BA increased the risk of permanent pacemaker implantation [22, 23, 30, 31, 33, 36] (OR: 2.46; 95% CI: 1.55–3.91; P=0.0001;I2 = 0%, Figure 7). No heterogeneity was observed.Figure 6
Cerebrovascular events.Figure 7
Permanent pacemaker implantation.


### 3.3. Sensitivity Analysis and Publication Bias

The risk of bias was comprehensively assessed according to the guidelines of the Cochrane Collaboration, and neither visual inspection of funnel plots nor Egger’s test detected significant publication bias for the major outcomes explored in this meta-analysis, including the prevalence of SR at discharge (t=0.04; P=0.972), SR at a 6-month follow-up (t=0.27; P=0.791), SR at a 12-month follow-up (t=0.90; P=0.401), SR after more than 1 year (t=0.52; P=0.626), early mortality (t=1.03; P=0.363), late mortality (t=-1.07; P=0.397), neurological events (t=51.13; P=0.012), and permanent pacemaker implantation (t=2.42; P=0.060). To evaluate the effect of heterogeneity on the pooled effect, we carried out a sensitivity analysis. Sensitivity and subgroup analyses found no significant heterogeneity (Table 4).Table 4
Sensitivity and subgroup analyses.
Endpoint Restored SR at discharge Restored SR at 12 months Restored SR beyond 1 year OverallP value OR (95% CI) OverallP value OR (95% CI) OverallP value OR (95% CI) Study design     0.46 1.37 (0.60, 3.11) RCT 0.38 0.51 (0.12, 2.25) Have no RCT studies 0.69 1.25 (0.43, 3.65) Non-RCT 0.4 1.17 (0.81, 1.68) Study size <150 0.88 1.05 (0.56, 1.95) 0.04 1.76 (1.02, 3.04) 0.76 1.22 (0.24, 4.46) >150 0.96 0.99 (0.66, 1.49) 0.44 1.29 (0.67, 2.48) 0.3 1.44 (0.73, 2.85) Statistical models Fixed-effect 0.3 1.12 (0.90, 1.38) 0.009 1.39 (1.09, 1.79) 0.16 1.21 (0.92, 1.59) Random-effect 0.34 1.15 (0.86, 1.55) 0.2 1.37 (0.85, 2.21) 0.4 1.31 (0.70, 2.48) SR: sinus rhythm; RCT: randomized, controlled trial.


## 3.1. Assessment of Efficacy

The data were pooled from 16 studies [12–15, 21–26, 28, 29, 31–33, 36] that assessed the efficacy of restoring sinus rhythm (SR), and the results showed that there was no significant difference between the BA and LA groups at discharge (78.3% versus 73.86%; OR: 1.02; 95% CI: 0.69–1.51; P=0.92;I2 = 66%). However, the overall prevalence of SR was higher in the BA group than in the LA group at a 6-month follow-up (78.82% versus 69.67%; OR: 1.54; 95% CI: 1.17–2.03; P=0.002;I2 = 0%) [14, 15, 22, 24–26, 30–32, 36]. For patients with a follow-up at 12 months [8, 14, 15, 26, 27, 30, 31, 34] and after more than 1 year [12, 15, 23–25, 31], the prevalence of SR in the BA group was similar to that in the LA group (63.01% versus 65.47%; OR: 1.31; 95% CI: 0.70–2.48; P=0.40;I2 = 77%). The weighted average mean follow-up for studies reporting SR after more than 1 year was 23.3 months. These results are shown in Figure 3.Figure 3
Restored SR at discharge, 6 months, and 12 months and beyond 1 year.


## 3.2. Mortality and Major Complications

Eight studies with 1185 patients investigated mortality after the BA or LA procedure. When effects were pooled, there was no significant difference in either early mortality [8, 14, 23, 27–29, 33] (<30 days, OR: 1.02; 95% CI: 0.36–2.90; P=0.97;I2 = 31%, Figure 4) or late mortality [23, 27, 29, 31, 35] (OR: 2.31; 95% CI: 0.86–6.22; P=0.10;I2 = 0%, Figure 5) between the BA and LA groups.Figure 4
Mortality within 30 days.Figure 5
Late mortality.There was no significant increase in the risk of cerebrovascular events [8, 27, 28, 31] between the two groups (OR: 0.61; 95% CI: 0.16–2.40; P=0.48;I2 = 0%, Figure 6). In eight studies that compared LA with BA, BA increased the risk of permanent pacemaker implantation [22, 23, 30, 31, 33, 36] (OR: 2.46; 95% CI: 1.55–3.91; P=0.0001;I2 = 0%, Figure 7). No heterogeneity was observed.Figure 6
Cerebrovascular events.Figure 7
Permanent pacemaker implantation.


## 3.3. Sensitivity Analysis and Publication Bias

The risk of bias was comprehensively assessed according to the guidelines of the Cochrane Collaboration, and neither visual inspection of funnel plots nor Egger’s test detected significant publication bias for the major outcomes explored in this meta-analysis, including the prevalence of SR at discharge (t=0.04; P=0.972), SR at a 6-month follow-up (t=0.27; P=0.791), SR at a 12-month follow-up (t=0.90; P=0.401), SR after more than 1 year (t=0.52; P=0.626), early mortality (t=1.03; P=0.363), late mortality (t=-1.07; P=0.397), neurological events (t=51.13; P=0.012), and permanent pacemaker implantation (t=2.42; P=0.060). To evaluate the effect of heterogeneity on the pooled effect, we carried out a sensitivity analysis. Sensitivity and subgroup analyses found no significant heterogeneity (Table 4).Table 4
Sensitivity and subgroup analyses.
Endpoint Restored SR at discharge Restored SR at 12 months Restored SR beyond 1 year OverallP value OR (95% CI) OverallP value OR (95% CI) OverallP value OR (95% CI) Study design     0.46 1.37 (0.60, 3.11) RCT 0.38 0.51 (0.12, 2.25) Have no RCT studies 0.69 1.25 (0.43, 3.65) Non-RCT 0.4 1.17 (0.81, 1.68) Study size <150 0.88 1.05 (0.56, 1.95) 0.04 1.76 (1.02, 3.04) 0.76 1.22 (0.24, 4.46) >150 0.96 0.99 (0.66, 1.49) 0.44 1.29 (0.67, 2.48) 0.3 1.44 (0.73, 2.85) Statistical models Fixed-effect 0.3 1.12 (0.90, 1.38) 0.009 1.39 (1.09, 1.79) 0.16 1.21 (0.92, 1.59) Random-effect 0.34 1.15 (0.86, 1.55) 0.2 1.37 (0.85, 2.21) 0.4 1.31 (0.70, 2.48) SR: sinus rhythm; RCT: randomized, controlled trial.


## 4. Discussion

Two recent meta-analyses [10, 11] that compared BA, LA, and surgical ablation in AF arrived at conflicting conclusions. However, these meta-analyses excluded several studies that compared BA with LA [8, 12–15, 25]. Therefore, we performed a new meta-analysis to compare BA with LA. This meta-analysis included three RCTs and 18 retrospective studies that collectively contained 3609 patients and compared the efficacy and safety of BA and LA. There was no significant difference between BA and LA in the rate of restored SR, but BA groups had a higher probability of SR after 6 months of follow-up. We also found that while BA and LA had similar rates of death and cerebrovascular events, the BA groups had a higher rate of permanent pacemaker implantation.A pooled analysis of restored postoperative SR showed that there was no difference between the BA and LA groups. However, several recent studies [21, 23, 36] have shown that BA is inferior to the more complete LA when used alone. Patients in the LA group had shorter aortic cross-clamping times and cardiopulmonary bypass times than were observed in the BA group. Furthermore, the techniques used in AF ablation vary widely, even within the same procedure group, and if the different lesion sets used for ablation were included, the results may have indicated that this procedure has greater efficacy.In contrast, some studies have reported that BA is superior to LA for restoring SR [8, 12, 15, 25–28, 30–33]. This finding rests mainly on the finding that BA groups have much more tissue damage and a higher rate of cardiac conduction system injury. However, all of these studies have common limitations. First, some patients took antiarrhythmic drugs (including amiodarone) perioperatively and continued the use of these drugs until the operation, and few researchers sufficiently addressed this variable. Second, the sample size in most of the articles was small (less than 150 individuals), weakening the power of the studies. Third, long rhythm registration during follow-up was not available in all of the patients. Furthermore, only a few of the studies were RCTs. Unlike previous reviews, we included the largest studies in our meta-analysis, and our inclusion criteria did not limit our search to articles published in English. We also conducted a subgroup analysis of RCT and non-RCT studies and of small-sample and large-sample studies to assess the effect of heterogeneity on the pooled effect estimate.The findings of the present meta-analysis confirm that BA increases the risk of permanent pacemaker implantation. This finding may be attributed to the fact that LA has shorter aortic cross-clamping and cardiopulmonary bypass times and promotes more extensive lesions. There was no significant increase in the risk of cerebrovascular events or early and late mortality between the two groups. We hypothesize that report selection resulted in fewer such events, and these results remain to be discussed.The most important findings of our meta-analysis include the following: (1) LA and BA were equally effective in restoring SR, (2) BA resulted in higher prevalence of SR at the 6-month follow-up, and (3) unlike previous analyses, this meta-analysis included the largest studies, and its inclusion criteria did not limit the search to articles published in the English language.The results of our study show that there was no difference in the rate of restored SR between LA and BA. While some previous studies have proposed that BA alone is inferior to a more complete LA, this significance disappeared in a multivariate analysis. The difference in these results may have been caused by differences in inclusion criteria between previous studies and our study. The other studies limited inclusion to articles reported in the English language. Additionally, the techniques used for AF ablation varied widely, including, for example, the use of different lesion sets, even within same procedure group.One of the most important reasons that researchers have suggested for why BA is better than LA at restoring SR is that there is a significant difference in electrical activity between patients with chronic and paroxysmal AF [37, 38]. Lazar et al. [37] demonstrated that a left-to-right atrial frequency gradient exists in paroxysmal but not persistent AF. This prompted them to propose that the maintenance of persistent or chronic AF may be less dependent on the posterior left atrium. Additionally, Sanders et al. [39] proposed that, in patients with paroxysmal AF, the dominant sources of activity are often localized in the pulmonary veins. In contrast, in patients with permanent AF, the dominant sites are more often localized in the atria, including right atrial sites. Unsurprisingly, patients with persistent or long-standing persistent AF are more likely to receive BA, and this may affect clinical outcomes [25].The present meta-analysis has the following limitations. Its main limitation is that only three small-sample RCTs were included. Inadequate random sequence generation and blinding tend to increase the risk of bias. Hence, larger RCTs are needed to determine the best treatment. Another limitation is that the original meta-analysis was based on the assumption that the surgical subgroups (BA and LA) were sufficiently similar to be assessed together, but the operation methods and ablation technologies used in these procedures are continually developing. Additionally, there was extreme heterogeneity among the studies in study design, data, and energy source, and a subgroup analysis yielded results that differed from those obtained in the original analysis. Future systematic reviews should, when sufficient literature is available, evaluate different indications separately. Finally, follow-up periods were generally short. Therefore, the long-term outcomes of BA and LA remain to be explored.


## 5. Conclusion

In this comparative meta-analysis, we show that BA is not more efficacious than LA in restoring SR. Additionally, the risks of death and cerebrovascular events are significantly different between BA and LA, but BA results in a higher rate of permanent pacemaker implantation.



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*Source: 3651212-2018-04-29.xml*