In patients with an enlarged left atrium does left atrial size reduction improve maze surgery success?

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1 doi: /icvts Interactive CardioVascular and Thoracic Surgery 13 (2011) Best evidence topic - Arrhythmia In patients with an enlarged left atrium does left atrial size reduction improve maze surgery success? Nicholas Sunderland a, Myura Nagendran b, *, Mahiben Maruthappu b a St Hugh's College, University of Oxford, St Margaret's Road, Oxford, OX2 6LE, UK b Green Templeton College, University of Oxford, Oxford, OX2 6H6, UK Received 24 April 2011; received in revised form 23 July 2011; accepted 1 August 2011 Summary A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was: In [adults undergoing a maze procedure for Atrial Fibrillation (AF)], [does Left Atrial size reduction] compared to [maze surgery alone] improve [maze surgery success]? A total of 58 papers were found using the reported search, of which eight represented the best evidence to answer the clinical question. The authors, journal, date and of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Four out of eight papers compared a volume reduction technique as an adjunct to the maze procedure to a maze procedure alone all four papers reported that atrial volume reduction significantly increased restoration of sinus rhythm: 89.3% vs. 67.2%, P<0.001; 85% vs. 68%, P<0.05; 84% vs. 68%, P<0.05; 90% vs. 69%, P<0.05. Three out of eight papers had no control group but reported good rates of sinus rhythm restoration at last follow-up 90%, 92% and 89%, respectively despite the study population including atrial enlargement, a risk factor for failure of a maze procedure. One paper reported no benefit of an atrial reduction plasty in patients with a left atrium (LA) >70 mm. An enlarged LA is a risk factor for failure of a maze procedure, and various models of AF suggest that reducing atrial mass and/or diameter may help to abolish the re-entry circuits underlying AF. Furthermore, AF is uncommon when left atrial diameter is <40 mm, so there is at least some physiological basis for atrial reduction surgery in aiding the success of a maze procedure. The evidence suggests that patients with an enlarged ( 55 mm) or giant ( 75 mm) LA who are at risk of failing to obtain sinus conversion after a standard maze procedure may derive benefit from concomitant atrial reduction surgery using either a tissue excision or a tissue plication technique. However, the evidence is not strong since the papers available are not readily comparable owing to substantial variations in the populations and procedures involved. We therefore, emphasise the need for prospective randomised studies in this area Published by European Association for Cardio-Thoracic Surgery. All rights reserved. Keywords: Atrial fibrillation; Cox maze; Left atrial size reduction; maze, Mini-maze; Recurrence of atrial fibrillation 1. Introduction A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1]. 2. Three-part question In [adults undergoing a maze procedure for Atrial Fibrillation (AF)], [does Left Atrial size reduction] compared to [maze surgery alone] improve [maze surgery success]? 3. Clinical scenario You are discussing the operative options for a patient requiring a mitral valve repair who has had permanent AF for two years. His echo shows a P2 prolapse but also a left atrial diameter of 7 cm. He would ideally like to come off warfarin and also gets troublesome palpitations, so is keen *Corresponding author. Green Templeton College, University of Oxford, Woodstock Road, OX2 6HG, UK. Tel.: ; fax: address: myura.nagendran@medschool.ox.ac.uk (M. Nagendran) Published by European Association for Cardio-Thoracic Surgery for you to do something about the AF. You feel that a maze procedure is unlikely to work in such a large atrium, but you have never embarked on a left atrial reduction before. This might be your first case to do this in, but before embarking on this you decide to check the literature to verify that it will make a significant difference to your chances of success. 4. Search strategy Medline search 1948 to February 2011 using PubMed interface (Atrial Fibrillation[MeSH Terms] OR Atrial Fibrillation OR AF[Ti]) AND (Cox Or maze OR Mini-maze) AND (Left atri* OR Size OR Enlarge* OR Giant OR Massive*) AND (reduce OR reduct*) A reverse citation search was then performed on all relevant papers in order to find further papers. Additionally, the Cochrane Database of Systematic Reviews was also searched for further relevant studies; no papers were found.

2 636 N. Sunderland et al. / Interactive CardioVascular and Thoracic Surgery 13 (2011) Table 1. Best evidence papers Wang et al., (2010), 322 patients with permanent SR at 12 months VR: 89.3% SR restoration was Eur J Cardiothorac AF and biatrial atrial Control: 67.2% significantly greater in Surg, USA, enlargement plus mitral P<0.001 the group that received [2] (±tricuspid) valve rheumatic LA wall tension VR: 4012±1650 dyn/cm VR despite the mean disease (at discharge) Control: 20,384±3313 dyn/cm preopererative LA Multicentre Randomised into two P<0.001 diameter being greater randomised study groups: than that of the control (level 1b) group VR group (n=166): atrial LA wall tension VR: 1059±1161 dyn/cm reduction plasty with reef (one year) Control: 17,139±3170 dyn/cm Follow-up: 96% of imbricate suture technique P<0.001 patients concomitant with the LA diameter in Preoperative: 64±12 mm Mean follow-up: 19±16 months maze procedure and VR group Discharge: 51±11 mm aggressive postoperative P<0.001 ELA: 55 mm pharmacological therapy LA diameter in Preoperative: 56±17 mm GLA: 75 mm (amiodarone, dieresis, control group Discharge: 49±8 mm intravenous Natrecor and P=not stated Oral amiodarone (orsotalol), oral Viagra) LA diameter VR: 43±7 mm 200 mg twice daily and change Control: 61±11 mm Viagra 25 mg daily were Control group (n=166): (discharge to one P<0.001 continued for 3 6 months treated with the maze year) after hospital discharge. procedure alone If a patient was not able to 135 males, 187 females, LA wall VR: 3.9±1.3 mm tolerate amiodarone mean age 45 ± 9.5 years thickness (one Control: 2.3±0.9 mm postoperatively, then sotalol year) P<0.005 was used for the same duration Modified full Cox maze-iii procedure using 20% (67/322) had supplemental RF ablation electrical cardioversion and bilateral atrial appendage 3% (10/322) required resection plus mitral valve permanent pacemaker replacement implantation for completed AV block Operations took place in three hospitals in China and one hospital in the USA Limitations: 1. The study group received not only VR, but also aggressive pharmacological therapy so the exact contribution of the VR cannot clearly be defined. 2. The statistics for the Patient demographics table are not presented notably, the relationship between the preoperative LA diameter in the two groups is not commented on Wang et al., (2010), 122 patients with permanent SR at discharge ELA: 83% (69/83) This study Interact Cardiovasc AF and LA enlargement GLA: 56% (22/39) demonstrated that LA Thorac Surg, USA, SR at 12-month 76% (93/122) reduction surgery in [3] 51 males, 71 females; mean follow-up combination with a age 45±9.5 years maze procedure is Multicentre SR at follow-up ELA: 90% (72/80)* relatively effective in retrospective cohort ELA=LA diameter 55 but GLA: 58% (21/36)* treating people with study <75 mm ELA (level 2b) GLA=LA diameter 75 mm Median follow-up: 19±16 The mortality was 0 in months (range 1 58 months) ELA group and 3 (2%) in the GLA group

3 N. Sunderland et al. / Interactive CardioVascular and Thoracic Surgery 13 (2011) Modified full Cox maze-iii *ELA group had a higher rate Long-term follow-up procedure using RF ablation of SR at 12-month follow-up was 96% complete and biatrial reduction with (P=0.05; values not the reef imbricate technique presented) concomitantly with mitral±tricuspid valve All patients received the surgery Preoperative LA ELA: 64±12 mm anti-arrhythmic diameter GLA: 86±17 mm medication amiodarone in the perioperative LA diameter ELA: 49±8 vs. 64±12 period. Electrical (discharge vs. P=0.01 cardioversion was preoperative) performed prior to GLA: 51±11 vs. 86±17 hospital discharge in any P=0.004 patient not in SR In patients with symptoms, such as palpitations and other evidence of atrial arrhythmias, a 48-h Holter monitor recording was obtained 37% (46/122) underwent electrical cardioversion This study is severely limited due to the lack of a control group Marui et al., (2008), 74 patients with chronic SR at last follow- Total: 78% (58/74) SR restoration was J Thorac Cardiovasc (permanent or persistent) up significantly greater in Surg, Japan, AF and mitral valve disease VR: 85% (39/46) the group that received [4] Control: 68% (19/28) LA reduction surgery All had LA diameter 60 mm P<0.05 Single-centre One patient died of a retrospective cohort Mean follow-up: 13.8±5.9 non-cardiac event after study months discharge (level 2b) VR group (n=46): patients underwent the maze Maximum LA VR preoperatively: 354±89 ml The maze procedure procedure concomitant with volume VR one month postoperatively: concomitant with LA the LA reduction surgery 157±35 ml VR surgery also and mitral valve surgery P<0.001 improved LA geometry and promoted LA Control group (n=28): Control preoperatively: 312±86 reverse remodelling patients underwent the ml during the one-year maze procedure+mitral Control one month follow-up valve surgery postoperatively: 275±70 ml P=NS maze procedures based on the modified Cox maze-iii with cryoablation Marui et al., (2007), 57 patients with chronic SR at 3 months VR: 84% (27/32) SR restoration at three Eur J Cardiothorac (permanent or persistent) Control: 68% (17/25) months was Surg, Japan, [5] AF and LA diameter >60 mm, P<0.05 significantly greater in plus mitral valve LA volume VR preoperatively: 291±117 ml the group that received Single-centre disease (end-diastolic) Control preoperatively: LA VR surgery retrospective cohort VR group (n=32): 223±81 ml study underwent the maze P<0.05 Limitations: (level 2b) procedure concomitant with not a prospective LA VR surgery VR postoperatively: 118±48 ml randomized study. The Control group (n=25): Control postoperatively: operation was not underwent the maze 203±76 ml randomly assigned for procedure alone P<0.001 the VR group or the control group

4 638 N. Sunderland et al. / Interactive CardioVascular and Thoracic Surgery 13 (2011) Maze procedures primarily VR: preoperatively vs. The follow-up period based on the modified Cox postoperatively was only three months maze-iii with cryoablation P<0.001 or LA maze procedure Control: preoperatively vs. Use of two types of the postoperatively. maze procedures might P=NS influence the results of the present study. LA ejection VR preoperatively: 8.4±4.2% However, the ratio of fraction (%) VR postoperatively: 22.3±7.8% patients who underwent P<0.001 the modified Cox maze- III or LA maze was not Control preoperatively. vs. significantly different postoperatively. between the groups P=NS (72% vs. 68%) Badhwar et al., 71 patients with permanent Mean LA Preoperatively: 67±12 mm LA reduction in (2006), AF and LA enlargement >55 mm diameter Postoperatively: 43±6 mm conjunction with an LA- Ann Thorac Surg, plus mitral valve disease P<0.001 only maze procedure USA, [6] and mitral value surgery 39 males, 32 females, mean SR (0 6-month 93% (25/27) was associated with Single-centre age 71.9±9.5 years follow-up) very good rates of sinus retrospective cohort conversion throughout study Combined LA reduction SR (7 12-months 94% (15/16) follow-up (mean (level 2b) with an LA-only modified follow-up) 10.7±8.4 months) Cox maze-iii lesion set during concomitant mitral SR (> one year 92% (23/25) One patient (1.4%) was valve surgery follow-up) lost to late follow-up and there were eight late deaths 42% (30/71) underwent cardioversion For current survivors with at least 12 months of follow-up, 12.5% (3/24) were on antiarrhythmic agents compared with 95.8% (23/24) at hospital discharge Limitations: sample size, the lack of a nonatrial reduction control group and poor rhythm data follow-up Romano et al., 36 patients with predictors SR 100% This study (2004), of maze operation failure (intraoperative) demonstrated a good Ann Thorac Surg, as entrance criteria: AF >six rate of sinus conversion USA, [7] months, AF waves <1 mm, SR at follow-up 89% (32/36) despite the presence of LA size >60 mm, and mitral Mean follow-up 19±16 months at least two classic Single-centre valve disease. (Patients had predictors of maze prospective cohort atleast two of these criteria; Mean LA 26% failure they attribute study most had all three.) diameter this to the aggressive (level 2b) reduction bilateral reduction 19 males, 17 females, mean postoperative plasty age 66 years No patient needed Full Cox maze-iii procedure electrical cardioversion. using supplemental RF Amiodarone was usually ablation, bilateral atrial discontinued at one appendage resections and month, but ultimately aggressive biatrial reduction this decision was by the plasty primary cardiologist

5 N. Sunderland et al. / Interactive CardioVascular and Thoracic Surgery 13 (2011) Mean LA diameter: 66±16 mm Late-term follow-up was 93% complete In a series by Kamata et al. [12], SR was restored overall in 68/86 patients (79%) and demonstrated an odds ratio of only 0.14 for restoration of SR in the presence of these fine fibrillatory waves. This cohort demonstrated significantly better results, with an 89% success rate despite the presence of fine fibrillatory waves Marui et al., (2006), 123 patients with chronic AF Preoperative LA VR: 67.1±7.8 mm Two (5%) patients in the J Thorac Cardiovasc diameter Control: 64.5±6.7 mm VR group and two (6%) Surg, Japan, [8] 80 had ELA (diameter >60 P=NS patients in the control mm) group received Single-centre SR at discharge VR: 82% (n=44) permanent pacemaker retrospective cohort VR group (n=44): Control: 75% (n=36) implantation study underwent maze procedure To maintain (level 2b) concomitantly with a novel SR at 12-month VR: 90% (n=30) postoperative SR, b- VR technique follow-up Control: 69% (n=36) blockers, digoxin or P<0.05 both were used unless Control group (n=36): otherwise underwent maze procedure SR at 24-month VR: 87% (n=15) contraindicated. If AF or alone follow-up Control: 67% (n=35) atrial flutter occurred, P<0.05 class I antiarrhythmic drugs were used. After Cox maze-iii or LA maze SR at 36-month VR: 100% (n=4) discharge, if patients procedure associated with follow-up Control: 64% (n=34) maintained SR, mitral valve surgery P<0.05 antiarrhythmic drugs were gradually LA diameter of VR preoperatively: 67.1±7.8 mm withdrawn one to three SR patients VR discharge: 47.6±6.3 mm months after the P<0.01 operation Control: preoperatively. LA diameter not significantly different from that at discharge or follow-up Follow-up was completed by outpatient clinic or telephone interview for all patients Limitations: this study was not a prospective randomized study; the operation was not randomly assigned for the VR group or the control group in a certain period; SR groups contained people who had had recurrent AF but happened to be in SR at follow-up; two types of maze procedure were used; the SR recovery rates in both groups at discharge were somewhat low compared with those of previous reports

6 640 N. Sunderland et al. / Interactive CardioVascular and Thoracic Surgery 13 (2011) Damiano et al., 282 patients with AF SR at 12 months 78% (n=187) Late follow-up available (2011), (without for all patients J Thorac Cardiovasc 177 males, 105 females, antiarrhythmics) Surg, USA, [9] mean age 63±12 years Risk factors for late SR at 12 months 89% (n=187) recurrence were Single-centre Mean duration of AF: 3.7 (with increasing preoperative prospective cohort years antiarrhythmics) LA diameter, but also a study 42% paroxysmal AF non-box lesion set and (level 2b) 10% persistent AF early postoperative 48% long-standing atrial tachyarrhythmias persistent AF Class I and III drugs Patient received either a Cox Probability of AF >50%* used until two months maze IV procedure alone recurrence if LA postoperatively (34%) or plus other cardiac diameter >80 mm *NB. All these patients will have surgery (66%) had an atrial reduction plasty Importantly, patients with an LA diameter Patients with an LA >70 mm received diameter >70 mm received reduction plasty, an atrial reduction plasty although this was not successful in preventing recurrence However, no data are presented on how many patients had an LA diameter >70 mm, or on exactly how the atrial reduction plasty was performed AF, atrial fibrillation; AV, atrioventricular; ELA, enlarged left atrium; GLA, giant left atrium; LA, left atrium; NS, not significant; RF, radiofrequency; SR, sinus rhythm; VR, volume reduction. 5. Search outcome A total of 56 papers were found using the reported PubMed search. Major inclusion criteria included the use of any maze surgery or its variations, a concomitant atrial size reduction plasty, and analysis in terms of maintenance of sinus rhythm postoperatively (success) vs. recurrence of AF (failure). From the search, eight papers were identified that provided evidence addressing the specific question. These are presented in Table Results Wang et al. [2, 3], report on a relatively large number of patients with permanent AF who received the modified maze-iii radiofrequency ablation procedure. In one study [2], they randomised 322 patients to receive either the maze-iii procedure (control group; n=166) or the maze- III procedure plus an reduction plasty of the left atrium (LA) using a reef-imbricate suture technique, with aggressive postoperative pharmacological therapy (study group; n=166). Restoration of sinus rhythm was significantly more frequent in the study group than in the control group at a one-year follow-up (89.3% vs. 67.2%; P<0.001). In a second study [3], Wang et al. report on a subset of these patients (n=122) with either an enlarged LA (ELA; mm) or a giant LA (GLA; 75 mm) who all received the aggressive bilateral atrial reduction with a reef imbricate technique as an adjunct to the Cox maze III procedure. At last follow-up (median 19±16 months), sinus rhythm had been restored in 72 of 80 patients (90%) in the ELA group, and 21 of 36 (58%) in the GLA group. Marui et al. [4] retrospectively analysed 74 patients with chronic AF and a LA diameter 60 mm into two non-randomised groups, one of which received a maze procedure alone (control group; n=28) and the other received a maze procedure plus LA reduction surgery using continuous horizontal mattress sutures to plicate the left atrium (study group, n=46). At mean follow-up (13.8±5.9 months), the rate of sinus conversion was significantly better in the LA reduction group (39 of 46; 85%) than in the control group (19 of 28; 68%), (P<0.05). Marui et al. [5] retrospectively analysed data from 57 patients with chronic AF and an LA diameter > 60 mm in two non-randomised groups, of which one received a maze procedure (control group; n=25) and the other of which received a maze procedure plus LA reduction surgery using continuous horizontal mattress sutures to plicate the left atrium (study group; n=32). Sinus rhythm restoration at the three-month follow-up was significantly greater in the volume reduction group (27 of 32; 84%) than in the control group (17 of 25; 68%), (P<0.05). Marui et al. [8] studied at 80 patients with chronic AF, mitral valve disease and an ELA (diameter >60 mm) in

7 N. Sunderland et al. / Interactive CardioVascular and Thoracic Surgery 13 (2011) two groups. One group underwent just a maze procedure (control group; n=36), whereas the other received LA volume reduction using a plication technique with continuous horizontal mattress sutures (study group; n=44). Sinus rhythm restoration was significantly better in the volume reduction group at 12, 24 and 36 months of follow-up (P<0.05). 7. Clinical bottom line An ELA is a risk factor for failure of a maze procedure, and various models of AF suggest that reducing atrial mass and/or diameter may help to abolish the re-entry circuits underlying AF. Four out of the eight papers compared a volume reduction technique as an adjunct to the maze procedure with a maze procedure alone all four papers reported that a reduction in atrial volume significantly increases restoration of sinus rhythm: 89.3% vs. 67.2%, P<0.001; 85% vs. 68%, P<0.05; 84% vs. 68%, P<0.05; 90% vs. 69%, P<0.05. Three out of eight papers had no control group but reported good rates of sinus rhythm restoration at last follow-up 90%, 92% and 89%, respectively despite the study population including patients with atrial enlargement, a risk factor for maze procedure failure. One paper reports no benefit from an atrial reduction plasty in patients with an LA diameter >70 mm. The concerns we have in answering this clinical question are several-fold: the majority of the available studies are retrospective and have a small population, most of the studies have short follow-up periods (usually one year or less), and four out of eight papers present no control group. There are also several important variations between studies, notably the aetiology of the AF, the type of maze procedure employed, the method of size reduction and the postoperative management. Overall, the evidence suggests that patients with an ELA ( 55 mm) or GLA ( 75 mm) who are at risk of failing to obtain sinus conversion after a standard maze procedure may derive benefit from concomitant atrial reduction surgery using either a tissue excision or a tissue plication technique. However, the evidence is not strong since the available papers are not readily comparable owing to substantial variations in the populations and procedures involved. We therefore, emphasise the need for prospective randomised studies in this area. References [1] Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003;2: [2] Wang W, Buehler D, Martland AM, Feng XD, Wang YJ. Left atrial wall tension directly affects the restoration of sinus rhythm after Maze procedure. Eur J Cardiothorac Surg 2011;40: [3] Wang W, Guo LR, Martland AM, Feng XD, Ma J, Feng XQ. Biatrial reduction plasty with reef imbricate technique as an adjunct to maze procedure for permanent atrial fibrillation associated with giant left atria. Interact CardioVasc Thorac Surg 2010;10: [4] Marui A, Saji Y, Nishina T, Tadamura E, Kanao S, Shimamoto T, Sasahashi N, Ikeda T, Komeda M. Impact of left atrial volume reduction concomitant with atrial fibrillation surgery on left atrial geometry and mechanical function. J Thorac Cardiovasc Surg 2008;135: [5] Marui A, Tambara K, Tadamura E, Saji Y, Sasahashi N, Ikeda T, Nishina T, Komeda M. A novel approach to restore atrial function after the maze procedure in patients with an enlarged left atrium. Eur J Cardiothorac Surg 2007;32: [6] Badhwar V, Rovin JD, Davenport G, Pruitt JC, Lazzara RR, Ebra G, Dworkin GH. Left atrial reduction enhances outcomes of modified maze procedure for permanent atrial fibrillation during concomitant mitral surgery. Ann Thorac Surg 2006;82: ; discussion [7] Romano MA, Bach DS, Pagani FD, Prager RL, Deeb GM, Bolling SF. Atrial reduction plasty Cox maze procedure: extended indications for atrial fibrillation surgery. Ann Thorac Surg 2004;77: ; discussion [8] Marui A, Nishina T, Tambara K, Saji Y, Shimamoto T, Nishioka M, Ikeda T, Komeda M. A novel atrial volume reduction technique to enhance the Cox maze procedure: initial results. J Thorac Cardiovasc Surg 2006;132: [9] Damiano RJ, Schwartz FH, Bailey MS, Maniar HS, Munfakh NA, Moon MR, Schuessler RB. The Cox maze IV procedure: predictors of late recurrence. J Thorac Cardiovasc Surg 2011;141:

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