Concomitant atrial fibrillation surgery for people undergoing cardiac surgery.

HHS Public Access Author manuscript Author Manuscript

Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22. Published in final edited form as: Cochrane Database Syst Rev. 2016 ; 2016(8): . doi:10.1002/14651858.CD011814.pub2.

Concomitant atrial fibrillation surgery for people undergoing cardiac surgery Mark D Huffman1, Kunal N Karmali1, Mark A Berendsen2, Adin-Cristian Andrei3, Jane Kruse4, Patrick M McCarthy5, and S C Malaisrie6 1Departments

of Preventive Medicine and Medicine (Cardiology), Northwestern University Feinberg School of Medicine, Chicago, IL, USA

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2Galter

Health Sciences Library, Northwestern University, Chicago, IL, USA

3Department 4Bluhm

of Surgery, Northwestern University, Chicago, IL, USA

Cardiovascular Institute, Northwestern Medicine, Chicago, IL, USA

5Division

of Cardiac Surgery, Northwestern University, Chicago, IL, USA

6Division

of Cardiac Surgery, Northwestern University, Chicago, IL, USA

Abstract

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Background—People with atrial fibrillation (AF) often undergo cardiac surgery for other underlying reasons and are frequently offered concomitant AF surgery to reduce the frequency of short- and long-term AF and improve short- and long-term outcomes.

Contact address: Mark D Huffman, Departments of Preventive Medicine and Medicine (Cardiology), Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA. [email protected]. CONTRIBUTIONS OF AUTHORS All review authors contributed to the development of the protocol. MAB developed the search strategy in conjunction with the other authors. MDH and KNK performed title and abstract screening, full-text reviewing, data extraction, risk of bias and GRADE assessments, and performed the statistical analyses. SCM resolved disagreements when necessary. MDH wrote the first draft, and all the other review authors provided critical edits and comments.

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DIFFERENCES BETWEEN PROTOCOL AND REVIEW We changed the postoperative rhythm outcome to match European Society of Cardiology/American Heart Association/American College of Cardiology/Heart Rhythm Society definition (freedom from atrial fibrillation, atrial flutter, and atrial tachycardia off antiarrhythmic drugs three months after surgery) and thus expanded our objective statement to include short-term outcomes. Because we found limited data beyond 12 months and because all trials reported freedom from atrial fibrillation, we changed a secondary outcome to include freedom from atrial fibrillation. We also changed the secondary outcome of “rhythm related intervention” to “permanent pacemaker implantation” based on data reported in the trials. We did not create an “Examination of outcome reporting bias” matrix or “Checklist to aid consistency and reproducibility of GRADE assessments” checklist. We limited our subgroups to individuals with and without paroxysmal atrial fibrillation; type of atrial fibrillation surgery (cut-and-sew maze versus other); and type of cardiac surgery (mitral valve surgery versus other). We did not add ’exp Controlled Clinical Trials as Topic/’ to the Cochrane precision-maximising RCT filter for MEDLINE. DECLARATIONS OF INTEREST This review is supported by a contract from the European Society of Cardiology to inform its 2016 clinical practice guidelines on the management of atrial fibrillation. MDH receives support from the World Heart Federation for its Emerging Leaders program through unrestricted educational grants from AstraZeneca, Boehringer Ingelheim, and Bupa. KNK has received support from a training grant from the NHLBI (T32 HL069771). AA is a steering committee member at Articure and received salary support in role of biostatistician for pilot study Implantable Monitor-Guided Anticoagulation for Non-Permanent AF from NIH/NHLBI. SCM receives honoraria from Edwards, Bolton, Baxter, and Abiomed for speaking and consulting activities. No other authors declare competing interest.

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Objectives—To assess the effects of concomitant AF surgery among people with AF who are undergoing cardiac surgery on short-term and long-term (12 months or greater) health-related outcomes, health-related quality of life, and costs. Search methods—Starting from the year when the first “maze” AF surgery was reported (1987), we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (March 2016), MEDLINE Ovid (March 2016), Embase Ovid (March 2016), Web of Science (March 2016), the Database of Abstracts of Reviews of Effects (DARE, April 2015), and Health Technology Assessment Database (HTA, March 2016). We searched trial registers in April 2016. We used no language restrictions. Selection criteria—We included randomised controlled trials evaluating the effect of any concomitant AF surgery compared with no AF surgery among adults with preoperative AF, regardless of symptoms, who were undergoing cardiac surgery for another indication.

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Data collection and analysis—Two review authors independently selected studies and extracted data. We evaluated the risk of bias using the Cochrane ‘Risk of bias’ tool. We included outcome data on all-cause and cardiovascular-specific mortality, freedom from atrial fibrillation, flutter, or tachycardia off antiarrhythmic medications, as measured by patient electrocardiographic monitoring greater than three months after the procedure, procedural safety, 30-day rehospitalisation, need for post-discharge direct current cardioversion, health-related quality of life, and direct costs. We calculated risk ratios (RR) for dichotomous data with 95% confidence intervals (CI) using a fixed-effect model when heterogeneity was low (I2 ≤ 50%) and randomeffects model when heterogeneity was high (I2 > 50%). We evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to create a ‘Summary of findings’ table.

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Main results—We found 34 reports of 22 trials (1899 participants) with five additional ongoing studies and three studies awaiting classification. All included studies were assessed as having high risk of bias across at least one domain. The effect of concomitant AF surgery on all-cause mortality was uncertain when compared with no concomitant AF surgery (7.0% versus 6.6%, RR 1.14, 95% CI 0.81 to 1.59, I2 = 0%, 20 trials, 1829 participants, low-quality evidence), but the intervention increased freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off antiarrhythmic medications > three months (51.0% versus 24.1%, RR 2.04, 95% CI 1.63 to 2.55, I2 = 0%, eight trials, 649 participants, moderate-quality evidence). The effect of concomitant AF surgery on 30-day mortality was uncertain (2.3% versus 3.1%, RR 1.25 95% CI 0.71 to 2.20, I2 = 0%, 18 trials, 1566 participants, low-quality evidence), but the intervention increased the risk of permanent pacemaker implantation (6.0% versus 4.1%, RR 1.69, 95% CI 1.12 to 2.54, I2 = 0%, 18 trials, 1726 participants, moderate-quality evidence). Investigator-defined adverse events, including but limited to, need for surgical re-exploration or mediastinitis, were not routinely reported but were not different between the two groups (other adverse events: 24.8% versus 23.6%, RR 1.07, 95% CI 0.85 to 1.34, I2 = 45%, nine trials, 858 participants), but the quality of this evidence was very low. Authors’ conclusions—For patients with AF undergoing cardiac surgery, there is moderatequality evidence that concomitant AF surgery approximately doubles the risk of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off anti-arrhythmic drugs while increasing the risk of permanent pacemaker implantation. The effects on mortality are uncertain. Future, highCochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22.

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quality and adequately powered trials will likely affect the confidence on the effect estimates of AF surgery on clinical outcomes.

PLAIN LANGUAGE SUMMARY Atrial fibrillation surgery for patients undergoing heart surgery Review question—What is the evidence about potential benefits and harms of concomitant atrial fibrillation surgery in people who have atrial fibrillation and are undergoing heart surgery?

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Background—People who undergo heart surgery may have an abnormal heart rhythm disorder known as atrial fibrillation, which increases the risk of developing a stroke. Some patients may experience symptoms of palpitations, and many patients are recommended to take blood thinners to reduce their risk of having a stroke. Many surgeons will offer patients a procedure to treat this heart rhythm disorder at the same time of a heart surgery. The aim of this systematic review was to assess the effects of this heart rhythm procedure, known as atrial fibrillation surgery, at the time of heart surgery. Study characteristics—We searched scientific databases in March 2016 and found 22 randomised trials (clinical studies where people are randomly put into one of two or more treatment groups) including 1899 adults that met our inclusion criteria. Most trials had at least one methodological limitation. Funding for most trials was either not reported or came from intramural funds or national funding bodies, including professional and governmental organisations.

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Key results—There is uncertainty about the effect of atrial fibrillation surgery on all-cause mortality because rates were similar between individuals who underwent the additional procedure to treat their atrial fibrillation and those who did not. Individuals who underwent this additional procedure were twice as likely to be free from atrial fibrillation and off medications three months following the surgery (51% [range: 39% to 62%] compared with 24%), but these individuals were also more likely to need a pacemaker following the procedure (7% [range: 5% to 10%] compared with 4%). Other outcomes, including procedural safety, stroke risk, and health-related quality of life were similar between the two groups, but there is uncertainty in the confidence of our estimates for these outcomes. We did not find any benefit of one type of atrial fibrillation surgical treatment compared with another.

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Quality of the evidence—The quality of evidence supporting atrial fibrillation surgery to treat atrial fibrillation is low to moderate because of the limitations of the original studies. It is likely that further research may influence these results.

Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22.

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SUMMARY OF FINDINGS FOR THE MAIN COMPARISON [Explanation] Concomitant atrial fibrillation surgery for people undergoing cardiac surgery Patient or population: individuals with atrial fibrillation who are undergoing cardiac surgery Setting: hospital Intervention: concomitant atrial fibrillation surgery Comparison: no atrial fibrillation surgery Outcomes

Anticipated absolute effects* (95% CI) Risk with no atrial fibrillation surgery

All-cause mortality

Study population

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66 per 1000 Freedom from AF/AFL/AT off antiarrhythmic medications > 3 months

Study population

Investigator-defined adverse events

Study population

241 per 1000

236 per 1000 Pacemaker implantation4

75 per 1000 (53 to 105)

492 per 1000 (393 to 615)

252 per 1000 (201 to 316)

Study population 41 per 1000

30-day mortality4

Risk with concomitant atrial fibrillation surgery

69 per 1000 (46 to 104)

Study population 23 per 1000

29 per 1000 (16 to 51)

Relative effect (95% CI)

No of participants (studies)

Quality of the evidence (GRADE)

RR 1.14 (0.81 to 1.59)

1829 (20 RCTs)

⊕⊕○○ LOW 1,2

RR 2.04 (1.63 to 2.55)

649 (8 RCTs)

⊕⊕⊕○ MODERATE 1

RR 1.07 (0.85 to 1.34)

858 (9 RCTs)

⊕○○○ VERY LOW 1,2,3

RR 1.69 (1.12 to 2.54)

1726 (18 RCTs)

⊕⊕⊕○ MODERATE 1

RR 1.25 (0.71 to 2.20)

1566 (18 RCTs)

⊕⊕○○ LOW 1,2

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*

The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1

Downgraded due to study limitations, largely driven by high risk of detection bias and small-study bias.

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2

Downgraded due to imprecision. 3 Downgraded due to publication (reporting) bias. 4 Individual adverse event related to procedural safety.


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BACKGROUND Description of the condition

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Atrial fibrillation (AF) is the most common cardiac arrhythmia and is characterised by an irregularly irregular rhythm caused by low-amplitude, supraventricular oscillations (Braunwald 2015). The estimated global prevalence of AF in 2010 was 33.5 million, including 20.9 million men (95% confidence interval (CI) 19.5 to 22.2) and 12.6 million women (95% CI 12.0 to 13.7) (GBD 2015). The lifetime risk for AF has been estimated at 26.0% (95% CI 24.0% to 27.0%) for men and 23.0% (95% CI 21.0% to 24.0%) for women (Lloyd-Jones 2004). Along with its related rhythm atrial flutter, AF was estimated to cause more than 114,000 global deaths and more than 3.6 million disability adjusted life years lost in 2010 (GBD 2015). Common causes of AF include diseases that affect cardiac structure: raised blood pressure, valvular heart disease, hypertrophic cardiomyopathy, and dilated cardiomyopathies, among others. Combined direct and indirect costs for AF in the USA were estimated at $12 billion in 2006, and direct and indirect costs for stroke were estimated at $34 billion in 2011 (Mozaffarian 2015).

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Atrial fibrillation can be categorised by its underlying patterns and time course. For example, AF that terminates spontaneously in less than seven days is considered paroxysmal, whereas AF lasting longer than seven days is persistent. Atrial fibrillation lasting more than one year is long-standing, whereas AF that is refractory to defibrillation or not considered by a physician or patient for rhythm control is considered permanent (Braunwald 2015). Different patterns of AF are thought to have different electrophysiological mechanisms. Rapid firing electrical drivers arising from the pulmonary veins may trigger and perpetuate paroxysmal AF, whereas multiple re-entrant wavefronts arising from the atria appear to underlie persistent AF.

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Atrial fibrillation can cause symptoms of palpitations, lightheadedness, and dyspnoea (shortness of breath), but may also be asymptomatic, particularly in older adults. Regardless of its pattern, the condition is associated with a four- to five-fold increased risk of stroke because of the potential for thrombus formation and subsequent thromboembolism (Wolf 1991). Risk factors for stroke in people with AF include age, sex (higher stroke risk in women), hypertension, heart failure, diabetes, and vascular disease, such as myocardial infarction, aortic disease, and prior stroke (Gage 2001). Anticoagulation with warfarin or non-vitamin K antagonists are the mainstays of therapy for stroke prevention in the majority of people with AF (Camm 2010; January 2014). In patients for whom a rhythm control strategy is selected, a variety of treatments can be employed, including direct current cardioversion, antiarrhythmic drugs, catheter-based radiofrequency ablation, cryoablation, left atrial appendage isolation, and surgical ablation-based techniques. People with AF often undergo cardiac surgery for other underlying reasons and are frequently offered concomitant AF surgery in an attempt to reduce the frequency of short- and long-term AF and improve short- and long-term outcomes (McCarthy 2013).


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Description of the intervention

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Atrial fibrillation surgery encompasses several techniques. The Cox maze operation was introduced in 1987 and has undergone several iterations to create an electrical maze that disrupts atrial wavelet propagation. At a minimum, the maze operation should include surgical ablation with: suture line from superior vena cava to inferior vena cava; suture line from inferior vena cava to the tricuspid valve; isolation of the pulmonary veins; isolation of the posterior left atrium; suture line from mitral valve to the pulmonary veins; management of the left atrial appendage (Calkins 2012).


The complex cut-and-sew maze operation has a low mortality rate (2%) and high efficacy rate (89% freedom from AF at 12 months; Damiano 2011). However, faster radiofrequency ablation, cryoablation, and high-intensity focused ultrasound techniques that isolate the pulmonary veins during cardiac surgery aim to mimic the cut-and-sew Cox maze suture lines and are commonly used as surgical alternatives (Malaisrie 2012), though it is believed that their effectiveness is lower than the classic cut-and-sew maze operation. These procedures modestly extend time on cardiopulmonary bypass and thus operative time, and may lead to an increased rate of postoperative pacemaker insertion, bleeding, or other adverse events. The effects of other interventions, such as ganglionic nerve plexus ablation and vagal denervation, are less well understood. Atrial fibrillation surgery also frequently includes left atrial appendage excision. Because the left atrial appendage is a common source of thrombus formation, its surgical excision may reduce the potential for thrombus formation and subsequent strokes. However, there are variations of the technique, including ligation, oversewing the base with or without excision, surgical stapling and excision, which may lead to differences in outcomes (January 2014). For example, follow-up echocardiography-based data suggest that as many as 50% of patients have incomplete appendage occlusion during postoperative follow-up (Kanderian 2008). How the intervention might work

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The cut-and-sew Cox maze operation electrically isolates the pulmonary veins with suture lines extending to the mitral valve annulus, both left and right atrial appendages, and the coronary sinus (Camm 2010). This operation creates a complex pathway that interrupts both electrical drivers from the pulmonary veins in people with paroxsymal AF as well as wavefront propagation in people with persistent AF. Freedom from AF has been estimated to be as high as 75% to 95% at 15 years, but the complexity of the operation has limited its uptake. Other techniques such as radiofrequency ablation, cryoablation, and high-intensity focused ultrasound are faster and aim to electrically isolate the pulmonary veins. These operations have an estimated success rate of 85% at 12 to 18 months (Gaita 2005), but there are differences in patients, ablation techniques, and outcome ascertainment that might influence these results. Why it is important to do this review Concomitant AF surgery is common. Between 2005 and 2010, The Society for Thoracic Surgeons reported more than 91,000 operations to treat AF. Overall, 41% of people undergoing cardiac surgery with preoperative AF underwent concomitant surgical ablation, while only 5% of all AF operations were isolated AF ablation procedures (Ad 2012). Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22.

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Concomitant AF surgery with ablation has been demonstrated to be cost-effective in people undergoing mitral valve surgery, with an incremental cost-effectiveness ratio of $3,850 per quality adjusted life year compared with valve surgery alone (Quenneville 2009).

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Concomitant AF surgery receives a moderate (class IIa) recommendation from the American Heart Association/American College of Cardiology/Heart Rhythm Society 2014 guidelines (January 2014). However, this recommendation is based on expert opinion. The same committee also recommends left atrial appendage excision in people with AF undergoing cardiac surgery, but the recommendation is weak (class IIb), and again the level of evidence is based on expert opinion (January 2014). On the other hand, the 2010 European Society of Cardiology Guidelines for the Management of Atrial Fibrillation recommend that “surgical ablation of AF should be considered in patients with symptomatic AF who are undergoing cardiac surgery (class IIa/Level A evidence)” and “surgical ablation of AF may be performed in patients with asymptomatic AF undergoing cardiac surgery if feasible with minimal risk (class IIb: Level C evidence; Camm 2010).” Despite the high level of evidence rating for symptomatic patients, these recommendations are based on three observational studies and expert reviews (Cox 1991; Gaita 2005; Ngaage 2007).

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There are at least nine randomised controlled trials (RCTs) of concomitant AF surgery among people undergoing mitral valve surgery (January 2014), though substantial heterogeneity exists in terms of participants, types of AF and cardiac surgery, and methods of outcome assessment. However, data on clinical outcomes beyond freedom from atrial fibrillation or atrial tachyarrhythmias have been generally lacking. We seek to fill this gap in knowledge by performing a systematic review on the effects of concomitant AF surgery in people undergoing cardiac surgery, which informs the 2016 European Society of Cardiology 2016 guidelines on the management of AF (ESC 2016).

OBJECTIVES To assess the effects of concomitant atrial fibrillation (AF) surgery among people with AF who are undergoing cardiac surgery on short-term and long-term (12 months or greater) health-related outcomes, health-related quality of life, and costs.

METHODS Criteria for considering studies for this review Types of studies—We included randomised controlled clinical trials (RCTs).

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Types of participants—We included studies that reported results from adults (18 years of age or older) with preoperative atrial fibrillation (AF), regardless of symptoms, who were undergoing cardiac surgery for another indication. Types of interventions—We investigated the following comparisons of intervention versus control/comparator.


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Intervention: Any concomitant atrial fibrillation surgery, including cut-and-sew maze, radiofrequency ablation, cryoablation, or high-intensity focused ultrasound with or without left atrial appendage excision or ligation. Comparator: No atrial fibrillation surgery. Concomitant cardiac surgery had to be the same in both the intervention and comparator groups to establish fair comparisons.

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Types of outcome measures—Outcomes are based on the recommendations by the 2012 consensus statement published by the Heart Rhythm Society, European Heart Rhythm Association, and the European Cardiac Arrhythmia Society outlining definitions and trial endpoints (Calkins 2012). This statement recommends a three-month “blanking period” after ablation when reporting outcomes. Primary outcomes •

All-cause mortality

•

Freedom from atrial fibrillation, flutter, or tachycardia off antiarrhythmic medications, as measured by patient electrocardiographic monitoring greater than three months after the procedure

•

Procedural safety (adverse events), including, but not limited to, 30-day mortality, permanent pacemaker, mediastinitis, cardiac tamponade, neurologic or thromboembolic event, need for surgical re-exploration, or adverse event defined by the investigators

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Secondary outcomes

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•

Cardiovascular mortality

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Fatal and non-fatal cardiovascular events, including myocardial infarction, stroke, transient ischaemic attack, or heart failure

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Freedom from atrial fibrillation

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30-day rehospitalisation

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Need for post-discharge direct current cardioversion

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Health-related quality of life measured by any validated and adjusted scale concerning quality of life

•

Direct costs

Search methods for identification of studies Electronic searches—On 31 March 2016, we searched the following sources from 1987 (the year the first maze operation was performed) of each database to the specified date and placed no restrictions on language of publication: •

Cochrane Library (Wiley)


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–

Cochrane Database of Systematic Reviews: Issue 3 of 12, March 2016

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Cochrane Central Register of Controlled Trials (CENTRAL): Issue 2 of 12, February 2016

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Database of Abstracts of Reviews of Effect (DARE): Issue 2 of 4, April 2015

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Health Technology Assessment Database (HTA): Issue 1 of 4, January 2016

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•

Ovid MEDLINE(R) 1946 to March Week 4 2016

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Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations March 30, 2016

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Embase 1974-present; Embase Classic 1947–1973; MEDLINE 1966present (embase.com)

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Conference Proceedings Citation Index-Science (CPCI-S) 1990-present (Web of Science)

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ClinicalTrials.gov (searched 1 April 2016)

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World Health Organization International Clinical Trials Registry Platform (http://apps-who-int/trialsearch/;-searched-1-A-2016 WHO ICTRP; http://apps.who.int/trialsearch/; searched 1 April 2016)

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See Appendix 1 for additional details related to our searches. We translated the MEDLINE strategy to the appropriate syntax for use in CENTRAL, Embase and other databases. We applied the Cochrane precision-maximising RCT filter for MEDLINE (Lefebvre 2011). For Embase, we translated from Ovid to embase.com syntax a multi-term Embase filter with the best balance of sensitivity and specificity (Wong 2006). When searching CPCI-S, we used a combination of keywords to try to limit retrieval to RCTs. Searching other resources—We tried to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, systematic reviews, meta-analyses, and health technology assessment reports. We also contacted study authors of included or registered trials to identify any further studies we may have missed. Data collection and analysis

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Selection of studies—Two review authors (MDH, KNK) independently scanned the abstract, title, or both, of every record retrieved to determine which studies to assess further. We investigated all potentially relevant articles as full text. We resolved any discrepancies through consensus or recourse to a third review author (SCM). If resolution of a disagreement was not possible, then we added the article to those ‘Awaiting assessment’ and contacted study authors for clarification. We present an adapted Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram showing the process of study selection (Liberati 2009) (Figure 1).


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Data extraction and management—For studies that fulfilled the inclusion criteria, two review authors (MDH, KNK) independently abstracted key participant and intervention characteristics and report data on efficacy outcomes and adverse events using standard data extraction templates, with any disagreements resolved by discussion, or, when required, by consultation with a third review author (SCM). We provide information including trial identifier about potentially relevant ongoing studies in the Characteristics of ongoing studies table. We tried to find the protocol of each included study and report primary, secondary, and other outcomes in comparison with data in publications. We emailed authors of included studies when we had questions about the status of the study or to request unpublished data.

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Dealing with duplicate and companion publications: In the event of duplicate publications, companion documents, or multiple reports of a primary study, we maximised the yield of information by collating all available data and used the most complete dataset aggregated across all known publications. In case of doubt, we gave priority to the publication reporting the longest follow-up associated with our primary or secondary outcomes. Assessment of risk of bias in included studies—Two review authors (MDH, KNK) assessed the risk of bias of each included study independently. We resolved disagreements by consensus, or by consultation with a third review author (SCM). We assessed risk of bias using The Cochrane Collaboration’s tool (Higgins 2011). We assessed the following criteria.

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Random sequence generation (selection bias)

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Allocation concealment (selection bias)

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Blinding of participants and personnel (performance bias) and of outcome assessors (detection bias)

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Incomplete outcome data (attrition bias)

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Selective reporting (reporting bias)

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Other potential sources of bias

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We judged ‘Risk of bias’ criteria as “low risk”, “high risk”, or “unclear risk” and evaluated individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We present a ‘Risk of bias’ graph (Figure 2) and ‘Risk of bias’ summary (Figure 3). We assessed the impact of individual bias domains on study results at the endpoint and study levels. In case of high risk of selection bias, we marked all endpoints investigated in the associated study as “high risk”. For performance bias (blinding of participants and personnel) and detection bias (blinding of outcome assessors), we evaluated the risk of bias separately for each outcome (Hróbjartsson 2013). We noted whether outcomes were measured subjectively or objectively. We considered the implications of missing outcome data from individual participants per outcome, such as high dropout rates (for example above 15%) or disparate attrition rates (for example difference of 10% or more between study arms). Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22.

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Measures of treatment effect—We expressed dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs). We expressed continuous data as mean differences (MDs) with 95% CIs. Unit of analysis issues—We planned to take into account the level at which randomisation occurred, such as cluster-randomised trials and multiple observations for the same outcome. However, all included trials were randomised at the individual-participant level.

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Dealing with missing data—We tried to obtain missing data from study authors, if feasible, and carefully evaluated important numerical data such as screened, randomised participants as well as intention-to-treat, and as-treated and per-protocol populations. We investigated attrition rates, for example dropouts, losses to follow-up, and withdrawals, and critically appraised issues of missing data and imputation methods. If standard deviations for outcomes were not reported, and we did not receive information from study authors, then we imputed these values by assuming the standard deviation of the missing outcome to be the average of the standard deviations from those studies where this information was reported. We investigated the impact of imputation on meta-analyses by means of sensitivity analysis.

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Assessment of heterogeneity—In the event of substantial clinical, methodological, or statistical heterogeneity (I2 greater than 50%), we either performed a random-effects metaanalysis with cautious interpretation or did not report study results as the pooled effect estimate in a meta-analysis. We tried to identify heterogeneity (inconsistency) through visual inspection of the forest plots and by using a standard Chi2 test with a significance level of α = 0.1. In view of the low power of this test, we also considered the I2 statistic, which quantifies inconsistency across studies, to assess the impact of heterogeneity on the metaanalysis (Higgins 2002; Higgins 2003). If we found substantial heterogeneity, then we attempted to determine possible reasons for it by examining individual study and subgroup characteristics. Assessment of reporting biases—Because we included more than 10 studies investigating a particular outcome, we used funnel plots to assess small-study effects. Several explanations can be offered for the asymmetry of a funnel plot, including true heterogeneity of effect with respect to trial size, poor methodological design (and hence bias of small trials), and publication bias. We therefore interpreted these results carefully (Sterne 2011).

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Data synthesis—We undertook meta-analyses only if the treatments, participants, and the underlying clinical questions in the studies were similar enough for pooling to be appropriate (Wood 2008). If an I2 was less than or equal to 50%, then we used a fixed-effect model, whereas if the I2 was greater than 50%, then we used a random-effects model (Higgins 2011). Quality of evidence—We present the overall quality of the evidence for important outcomes according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which takes into account issues not only related to internal Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22.

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validity (risk of bias, inconsistency, imprecision, publication bias), but also to external validity, such as directness of results. Two review authors (MDH, KNK) independently rated the quality for important outcomes. We present a summary of the evidence in a ‘Summary of findings’ table, which provides key information about the best estimate of the magnitude of the effect, in relative terms and absolute differences for each relevant comparison of alternative management strategies, numbers of participants and studies addressing each important outcome, and the rating of the overall confidence in effect estimates for each outcome. We created the Summary of findings for the main comparison based on the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We present results on the outcomes as described in the Types of outcome measures section.

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Subgroup analysis and investigation of heterogeneity—Because we expected the following characteristics to introduce clinical heterogeneity, we carried out subgroup analyses with investigation of interactions. •

Paroxysmal versus persistent AF (paroxysmal AF studies defined post-hoc as including ≥ 50% of participants)

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Type of AF surgery (cut-and-sew versus radiofrequency ablation)

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Type of cardiac surgery (mitral versus non-mitral cardiac surgery)

Sensitivity analysis—We had proposed performing sensitivity analyses to explore the influence of the following factors on effect sizes.

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Restricting the analysis to published studies

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Restricting the analysis by taking into account risk of bias, as specified in the Assessment of risk of bias in included studies section

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Restricting the analysis to very long (> five years) or large (> 500 participants) studies to establish the extent to which they dominate the results

However, we were unable to complete this sensitivity analysis because we did not have data for unpublished studies; all but one (Doukas 2005) of the identified studies were assessed as having high or unclear risk of bias across two or more domains, and there were no studies with follow-up > five years or with > 500 participants.

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Description of studies Results of the search—Appendix 1 describes the search details, and Figure 1 includes the PRISMA flow chart of included studies. After de-duplication, we screened 4976 titles and abstracts. We excluded 4877 irrelevant records from which 99 study reports remained for full-text review. We removed an additional four duplicate records and assessed 95 fulltext reports for eligibility. We excluded 61 studies and reasons for full-text exclusion are shown in Characteristics of excluded studies. We also reviewed the full text of nine clinical


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trial register records, from which we excluded one study, identified five studies that are ongoing (Characteristics of ongoing studies) and three studies awaiting classification (Characteristics of studies awaiting classification). We contacted study authors of all ongoing studies and studies awaiting classification for further details to determine inclusion in this review but received little to no response from authors. One author reported low recruitment in the study, but other trial details were not provided (NCT01791218). In total, we included a total of 34 reports of 22 trials randomising 1899 participants (Characteristics of included studies).

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Included studies—Table 1 summarises the included studies. Trials were reported between 2001 and 2015. Most (17/22) trials were small (< 200 participants) and were performed in a single centre or country, including nine trials in low- or middle-income countries. The mean age in each arm ranged from 36 years (Srivastava 2008) to 75 years (Knaut 2010), and the proportion of women in each arm ranged from 16% (Jonsson 2012) to 73% (Vasconcelos 2004). Only two trials (Pokushalov 2012; Vasconcelos 2004) included only participants with paroxysmal atrial fibrillation (AF), and only two trials did not have a majority of participants undergoing mitral valve surgery (Knaut 2010; Pokushalov 2012) with a high proportion of rheumatic heart disease present in most trials. Three trials used a cut-and-sew technique (Albrecht 2009; Jessurun 2003; Vasconcelos 2004), three trials used a microwave ablation technique (Jonsson 2012; Knaut 2010; Schuetz 2003), two trials exclusively used cryoablation (Blomstrom-Lundqvist 2007; Budera 2012), and the remaining trials used either monopolar or bipolar radiofrequency ablation.

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Excluded studies—We excluded 61 full-text reports and one trial registry record. The most common reason for exclusion was wrong study design (39 reports). Other studies were excluded because they: tested the wrong intervention (eight reports), used the wrong comparator (six reports), studied the wrong patient population (five reports), and had an incorrect citation listed in the search database (one report). One German-language report was excluded because we were unable to identify evidence of a full-text record in spite of library searches, interlibrary loan requests, and multiple emails to the author team (Lemke 2000). Two trials were excluded because the studies were terminated before any participants were recruited (NCT00157807; Vicol 2005). Risk of bias in included studies

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Figure 2 and Figure 3 demonstrate overall and trial specific information on risk of bias. All included studies were assessed as having high risk of bias across at least one domain. ‘Risk of bias’ assessments across each domain are summarised below, and detailed documentation supporting each assessment is included in the Characteristics of included studies table. Allocation—There were nine trials that adequately reported the methods used for random sequence generation and were assessed as having low risk of bias (Blomstrom-Lundqvist 2007; Chevalier 2009; de Lima 2004; Doukas 2005; Gillinov 2015; Jonsson 2012; Srivastava 2008; von Oppell 2009; Wang 2014). The remaining 13 trials were assessed as having unclear risk of bias. There were five trials that had a low risk of selection bias based on reported methods of allocation concealment (Cherniavsky 2014; Chevalier 2009; Doukas


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2005; Jonsson 2012; von Oppell 2009). All other trials were assessed as having unclear risk of bias. In total, four trials were assessed as having low risk of selection bias (low risk of bias for random sequence generation and allocation concealment) (Chevalier 2009; Doukas 2005; Jonsson 2012; von Oppell 2009). Blinding—Only two trials adequately reported blinding study personnel and participants for a low risk of performance bias (Blomstrom-Lundqvist 2007; Cherniavsky 2014). One trial was assessed as having an unclear risk of performance bias (Wang 2014) and the remaining 19 trials were assessed as having high risk of performance bias. Eight trials used blinded outcome assessors and were assessed as having low risk of detection bias (Cherniavsky 2014; Chevalier 2009; de Lima 2004; Doukas 2005; Gillinov 2015; Jonsson 2012; Pokushalov 2012; Wang 2014). Seven trials were assessed as having an unclear risk of bias and the remaining seven trials were assessed as having high risk of bias.

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Incomplete outcome data—Twelve trials had complete follow-up and were assessed as having low risk of bias in this domain (Abreu Filho 2005; Akpinar 2003; Albrecht 2009; Cherniavsky 2014; Chevalier 2009; Deneke 2002; Doukas 2005; Jessurun 2003; Knaut 2010; Pokushalov 2012; von Oppell 2009; Wang 2014). One trial (de Lima 2004) had unclear risk of bias in this domain. The remaining nine trials were assessed as having a high risk of bias.

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Selective reporting—Only four trials had low risk of reporting bias based on previously published protocols and adherence to those protocols (Budera 2012; Doukas 2005; Gillinov 2015; Wang 2014). Four trials were assessed as having high risk of reporting bias due to inadequate reporting of outcomes or major discrepancies between the trial registration and the published report (Blomstrom-Lundqvist 2007; de Lima 2004; Jonsson 2012; van Breugel 2010). The remainder were assessed as having unclear risk of reporting bias. Other potential sources of bias—Fifteen studies were assessed as having a high risk of other bias, of which small-study bias was the most frequent cause (Abreu Filho 2005; Akpinar 2003; Albrecht 2009; Blomstrom-Lundqvist 2007; Cherniavsky 2014; Chevalier 2009; de Lima 2004; Deneke 2002; Jessurun 2003; Khargi 2001; Knaut 2010; Pokushalov 2012; Schuetz 2003; Vasconcelos 2004; von Oppell 2009). Funding for most trials was either not reported or came from intramural funds or national funding bodies, including professional and governmental organisations.

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Figure 4 demonstrates funnel plot results for the outcome of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off anti-arrhythmic drugs and demonstrates no asymmetry, which suggests low risk of publication bias. On the other hand, Figure 5 demonstrates funnel plot asymmetry for the related, but less stringent outcome of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia regardless of anti-arrhythmic drug status, which suggests high risk of publication bias for this outcome. The effect of concomitant AF surgery, therefore, is likely closer to the estimated effect for the former outcome.


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Effects of interventions

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See: Summary of findings for the main comparison Concomitant atrial fibrillation surgery for people undergoing cardiac surgery Key results are reported in the Summary of findings for the main comparison, including overall results related to adverse events and specific outcomes related to procedural safety. Analyses 1–18 (Analysis 1.1; Analysis 1.2; Analysis 1.3; Analysis 1.4; Analysis 1.5; Analysis 1.6; Analysis 1.7; Analysis 1.8; Analysis 1.9; Analysis 1.10; Analysis 1.11; Analysis 1.12; Analysis 1.14; Analysis 1.15; Analysis 1.16; Analysis 1.17; Analysis 1.18) describe the forest plots for the effects of concomitant cardiac surgery on various outcomes. When trials had multiple intervention groups (Albrecht 2009, de Lima 2004), we combined these groups to estimate the general effect of atrial fibrillation (AF) surgery.

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Primary outcomes All-cause mortality: There was low-quality evidence demonstrating no difference in allcause mortality between individuals who underwent AF surgery and those who did not (7.0% in AF surgery group versus 6.6% in no AF surgery group; risk ratio (RR) 1.14, 95% confidence interval (CI) 0.81 to 1.59; I2 = 0%; 20 randomised controlled trials (RCTs), 1829 participants, Analysis 1.1), which highlights the uncertainty of the effect of AF surgery on this outcome.

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Freedom from atrial fibrillation, flutter, or tachycardia: There was moderate-quality evidence that concomitant AF surgery led to greater freedom from atrial fibrillation, atrial flutter, and atrial tachycardia off anti-arrhythmic medications > three months after surgery (51.0% in AF surgery group versus 24.1% in no AF surgery group; RR 2.04, 95% CI 1.63 to 2.55; I2 = 0%; eight RCTs, 649 participants, Analysis 1.2). The results were similar when the outcome was expanded to include freedom from atrial fibrillation, atrial flutter, or atrial tachycardia regardless of anti-arrhythmic drug use (60.1% in AF surgery group versus 24.4% in no AF surgery group; RR 2.46, 95% CI 2.16 to 2.80; I2 = 41%; 22 RCTs, 1899 participants, Analysis 1.3), but the quality of evidence for this effect estimate is low due to study limitations and publication bias.

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Procedural safety (adverse events): The rate of adverse of events defined by investigators was similar between the intervention and comparator group (24.8% in AF surgery group versus 23.6% in no AF surgery group; RR 1.07, 95% CI 0.85 to 1.34; I2 = 45%; nine RCTs, 858 participants, Analysis 1.4), but the quality of evidence for this outcome is very low. Specific adverse events are reported in Analysis 1.5 (permanent pacemaker implantation); Analysis 1.6 (30-day mortality); Analysis 1.7 (mediastinitis); Analysis 1.8 (cardiac tamponade); Analysis 1.9 (neurological or thromboembolic events); Analysis 1.10 (need for surgical re-exploration). The only individual adverse event that appeared higher in the intervention group was the need for permanent pacemaker implantation (6.9% in the AF surgery group versus 4.1% in no AF surgery group; RR 1.69, 95% CI 1.12 to 2.54; I2 = 0%; 18 RCTs, 1726 participants, Analysis 1.5, moderate-quality evidence).


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Secondary outcomes

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Cardiovascular mortality: There was uncertainty of any effect of AF surgery on cardiovascular mortality (3.6% in AF surgery group versus 1.4% in no AF surgery group; RR 1.82, 95% CI 0.72 to 4.60, I2 = 0%; nine RCTs, 496 participants, Analysis 1.11). Fatal and non-fatal cardiovascular events: There was uncertainty of any effect of AF surgery on fatal and non-fatal cardiovascular events (17.1% in AF surgery group versus 14.9% in no AF surgery group; RR 1.17, 95% CI 0.86 to 1.59, I2 = 0%; eight RCTs, 826 participants, Analysis 1.12).

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Freedom from atrial fibrillation: Using the less stringent definition of freedom from AF (Analysis 1.13), there was a similar direction and magnitude of effect, albeit higher effect size (63.6% in AF surgery group versus 24.2% in no AF surgery group; RR 2.55, 95% CI 2.01 to 3.24; I2 = 57%, 15 RCTs, 1500 participants). Thirty-day rehospitalisation: There was low-quality evidence of increased risk for 30-day re-hospitalisation (57.9% in the AF surgery group versus 42.5% in the no AF surgery group; RR 1.36, 95% CI, 1.06 to 1.75; one RCT, 260 participants, Analysis 1.14; downgraded due to study limitations and imprecision). Need for post-discharge direct current cardioversion: There was uncertainty of any effect of AF surgery on post-discharge direct cardioversion (21.2% in the AF surgery group versus 17.9% in no AF surgery group; RR 1.11, 95% CI 0.49 to 2.49, I2 = 63%; six RCTs, 352 participants, Analysis 1.15), although this outcome was poorly reported in most trials.


Health-related quality of life: Four trials (Cherniavsky 2014; Gillinov 2015; Jessurun 2003; van Breugel 2010) reported results on health-related quality of life but were too dissimilar to meta-analyse. There was no evidence of any difference in the overall healthrelated quality of life scores using validated instruments (e.g. EuroQoL, Short-Form-36 [SF-36]) between the intervention and comparator groups for each of these studies. Two trials (Gillinov 2015; van Breugel 2010) reported modest differences in either individual sub-scales or other instruments, including improvements in daily AF symptoms using the Atrial Fibrillation Severity Scale by Gillinov 2015 (19.8% in the AF surgery group versus 45.2% in the no AF surgery group, P < 0.001), but participants were not blinded in this trial, which likely influenced the reporting of this subjective outcome. One trial (Cherniavsky 2014) reported improvements in multiple domains (physical functioning, role-physical, bodily pain, general health, and role-emotional) of the SF-36 quality of life scale for AF surgery (either concomitant pulmonary vein isolation (PVI) or concomitant mini-Maze) compared with coronary artery bypass graft (CABG). However, results were mixed and in none of these domains were both AF surgery groups better than CABG alone. These results were not meta-analysed because sample size at baseline and follow-up were not presented by the authors. Direct costs: One trial (van Breugel 2010) reported results on costs and cost-effectiveness of AF surgery. The authors estimated that AF surgery costs an additional EURO74,724 (95%


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uncertainty interval (UI), EURO72,770, EURO76,678) and was not considered cost-effective with an incremental cost-effectiveness ratio of EURO73,359 per quality adjusted life year based on results from the EuroQoL instrument. Health-related quality of life data were also captured from the SF-36 instrument for this trial, which was not different between the intervention and control groups. These data were not used for incremental cost-effectiveness ratio estimates.

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Subgroup and sensitivity analyses: The direction and magnitude of the effect of the intervention on freedom from atrial fibrillation, atrial flutter, and atrial tachycardia was similar when evaluating the effect across different subgroups, including by: 1) presence of paroxysmal AF (RR 2.54, 95% CI 1.47 to 4.36; I2 = 48%; two RCTs, 70 participants, Analysis 1.16) (Jessurun 2003; Pokushalov 2012), 2) use of cut-and-sew maze (RR 2.49, 95% CI 1.60 to 3.87; I2 = 11%; four RCTs, 124 participants, Analysis 1.17) (Albrecht 2009; de Lima 2004; Jessurun 2003; Vasconcelos 2004), and 3) non-mitral valve surgery (RR 1.89, 95% CI 1.41 to 2.53; I2 = 3%; three RCTs, 175 participants, Analysis 1.18) (Cherniavsky 2014; Knaut 2010; Pokushalov 2012). We did not perform sensitivity analyses since all studies except one (Doukas 2005) were assessed as having high or unclear risk of bias across two or more domains. Moreover, we were unable to obtain data from any unpublished studies, and none of the identified studies included > 500 participants or follow-up for > five years.

DISCUSSION Summary of main results


The trials included in this systematic review demonstrate uncertainty regarding the effect of atrial fibrillation (AF) surgery on mortality. However, concomitant AF surgery, regardless of technique, approximately doubles the rate of freedom from atrial fibrillation, atrial flutter, and atrial tachycardia off anti-arrhythmic medications > three months after concomitant cardiac surgery from 24% to 51%. This outcome was only reported in a minority of the trials, primarily because other trials did not report anti-arrhythmic drug use. This intervention increases the risk for postoperative permanent pacemaker insertion from 4% to 7%. There is uncertainty of any effect of concomitant AF surgery on cardiovascular mortality, other adverse events, fatal or non-fatal cardiovascular events, neurological or thromboembolic events, or health-related quality of life. Data on costs and cost-effectiveness were infrequently reported, and this represents another area of uncertainty. Notably, most included trials were small and from single centres with heterogeneous types of participants, AF surgery, cardiac surgery, and methods of outcome assessment, though mitral valve surgery (86%) was the most common primary cardiac surgery. Overall completeness and applicability of evidence This review provides the most contemporary appraisal of evidence to date. We identified 34 reports of 22 trials from 14 countries (including five middle-income countries), three trials awaiting classification, and five ongoing trials compared with 16 trials (n = 1025 participants) identified by Phan 2014. Further, our systematic review incorporates the


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endpoint definition of procedural success, namely freedom from atrial fibrillation, atrial flutter, and atrial tachycardia off anti-arrhythmic drugs > three months post-procedure, as recommended by professional organisations (Calkins 2012). We further evaluated the potential for outcome assessment bias in trials reporting this outcome, since greater assessment of AF can lead to greater detection and thus greater procedural failure. We searched clinical trial registers and contacted study authors to seek unpublished data to guard against publication bias. We identified five ongoing clinical trials, though expected completion dates range widely. The sample sizes of these trials appear generally small and may not materially influence our results. We also identified three studies that await classification, for which we have insufficient information to categorise. These trials have either been terminated or have an unknown status but may contribute to the high risk of publication bias for the outcome of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia regardless of anti-arrhythmic drug status.

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Quality of the evidence

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Using the GRADE framework, our review demonstrates moderate-quality evidence evaluating the effect of the intervention on freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off anti-arrhythmic drugs, which was downgraded due to study limitations. The effects on all-cause mortality are uncertain based on low-quality evidence, and these data have been downgraded because of study limitations and imprecision. There is moderate-quality evidence that the intervention increases the risk for requiring a permanent pacemaker, and this evidence is downgraded due to study limitations. For the outcome of investigator-defined adverse events, the quality of evidence was very low and was downgraded due to study limitations, imprecision and publication bias. The quality of evidence evaluating the effects of the intervention on post-discharge cardioversion was very low due to study limitations, imprecision, and inconsistency of effect. Potential biases in the review process We were limited in our evaluation of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off anti-arrhythmic drugs by the trial reporting, which was generally insufficient to assess whether or not participants were receiving anti-arrhythmic drugs. Therefore, we were able to include only eight trials (649 participants) for this outcome. However, the magnitude and direction of this effect was similar when we used a less stringent outcome of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia, which was defined in 22 trials (1899 participants). Agreements and disagreements with other studies or reviews

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Our results demonstrated a lower success rate and smaller effect of concomitant AF surgery on restoration of sinus rhythm compared with Phan 2014 (one year 67% versus 26%, odds ratio (OR), 6.72; 95% CI 4.88 to 9.25), the most comprehensive and contemporary review prior to ours. Phan 2014 reported weighted mean averages of freedom from AF (75% versus 29%) and anti-arrhythmic drug use (36% versus 39%) at 12 months, but these outcomes were not integrated. Differences between our estimates and those from non-randomised studies are even greater. Our use of the more stringent, recommended endpoint definition of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off anti-arrhythmic drugs Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22.

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(Calkins 2012) contributes to this difference. Because of this difference, our estimate is likely closer to the true effect. We also demonstrated an increased risk for permanent pacemaker implantation, whereas Phan 2014 did not (6% versus 8%, OR 0.88; 95% CI 0.51 to 1.51). This difference is largely driven by the inclusion of Gillinov 2015, which was a large trial that had a pacemaker implantation rate of nearly 20% in the group that received concomitant AF surgery. Phan 2014 also demonstrated a lower risk of pericardial tamponade associated with concomitant AF surgery (2% versus 9%, OR 0.25; 95% CI 0.08 to 0.82), which was not demonstrated in our review. Other results between these reviews were generally similar.

AUTHORS’ CONCLUSIONS Implications for practice

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For patients with atrial fibrillation (AF) undergoing cardiac surgery, concomitant AF surgery approximately doubles the rate of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off anti-arrhythmic drugs from 24% to 51% (range: 39% to 62%), while increasing the risk of permanent pacemaker implantation from 4% to 7% (range: 5% to 10%). Due to trial heterogeneity and lack of direct comparison, it is uncertain if a particular type of AF surgery has greatest efficacy for AF treatment. There is uncertainty about the effects on all-cause or cardiovascular mortality, other adverse events, fatal or non-fatal cardiovascular events, neurological or thromboembolic events, or health-related quality of life. The effect of this intervention on post-discharge direct current cardioversion is uncertain given the very low quality of evidence for this outcome. Implications for research


Longer-term outcome assessment may help evaluate whether or not AF surgery influences neurological or thromboembolic risk, which is the primary goal of AF treatment for most physicians and patients. All trials had a high risk of bias across at least one domain, and future trials should emphasise strategies to reduce the risk of selection and detection bias, using implantable loop recorders and blinded outcome assessment committees for the latter, including adverse event assessment. Most trials did not report the co-primary outcome of freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off anti-arrhythmic drugs > three months after the procedure. Most trials also did not perform minimal follow-up screening for outcome assessment, nor did they report major complications as recommended by current professional organisations (Calkins 2012). Future trials can be improved by adhering to these performance and reporting standards to better evaluate the effect of AF interventions, including concomitant AF surgery. Large, high-quality randomised trials evaluating the effect of different AF surgery types and lesion sets (e.g. restricting lesion sets to the left atrium) and trials evaluating within AF subgroups (including only patients with paroxysmal, persistent, or long-standing persistent AF as recommended by professional organisations (Calkins 2012) could guide researchers, clinicians, and patients about which intervention has the most favourable efficacy and safety profile in which clinical situation.


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Acknowledgments Parts of the Methods section are based on a standard template established by the Cochrane Metabolic and Endocrine Disorders Group. SOURCES OF SUPPORT Internal sources •

Northwestern University Feinberg School of Medicine, USA.

The Cochrane Heart Group US Satellite is supported by intramural funding from Northwestern University Feinberg School of Medicine. External sources •

European Society of Cardiology, UK.

The production of this review has been supported by a contract from the European Society of Cardiology to inform its clinical practice guideline on atrial fibrillation.

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References to studies included in this review *Indicates the major publication for the study


Abreu Filho 2005 {published data only}. Abreu Filho CA, Lisboa LA, Dallan LA, Spina GS, Grinberg M, Scanavacca M, et al. Effectiveness of the maze procedure using cooled-tip radiofrequency ablation in patients with permanent atrial fibrillation and rheumatic mitral valve disease. Circulation. 2005; 112(9 Suppl):I20–5. [PubMed: 16159816] Akpinar 2003 {published data only}. Akpinar B, Guden M, Sagbas E, Sanisoglu I, Ozbek U, Caynak B, et al. Combined radiofrequency modified maze and mitral valve procedure through a port access approach: early and mid-term results. European Journal of Cardio-Thoracic Surgery. 2003; 24:223–30. [PubMed: 12895612] Albrecht 2009 {published data only}. Albrecht A, Kalil RA, Schuch L, Abrahao R, Sant’Anna JR, de Lima G, et al. Randomized study of surgical isolation of the pulmonary veins for correction of permanent atrial fibrillation associated with mitral valve disease. Journal of Thoracic and Cardiovascular Surgery. 2009; 138:454–9. [PubMed: 19619795] * Albrecht A, Kalil RA, de Lima GG, Miglioransa MH, Tigre E, Faria-Correa D, et al. Randomized study of surgical correction of permanent atrial fibrillation. Journal of the American College of Cardiology. 2005; 45:360A.Albrecht A, Lima G, Kalil RA, Faria-Corrêa DL, Miglioransa M, Abrahão R. Randomized study of surgical correction of permanent atrial fibrillation: preliminary results. Revista Brasileira de Cirurgia Cardiovascular. 2004; 19(3):295–300. Blomstrom-Lundqvist 2007 {published data only}. Blomstrom-Lundqvist C, Johansson B, Berglin E, Nilsson L, Jensen SM, Thelin S, et al. A randomized double-blind study of epicardial left atrial cryoablation for permanent atrial fibrillation in patients undergoing mitral valve surgery: the SWEDish Multicentre Atrial Fibrillation study (SWEDMAF). European Heart Journal. 2007; 28:2902–8. [PubMed: 17984136] * Johansson B, Bech-Hanssen O, Berglin E, Blomstrom P, Holmgren A, Jensen SM, et al. Atrial function after left atrial epicardial cryoablation for atrial fibrillation in patients undergoing mitral valve surgery. Journal of Interventional Cardiac Electrophysiology. 2012; 33:85–91. [PubMed: 21935581] Budera 2012 {published data only}. Budera P, Straka Z, Osmancik P, Vanek T, Jelinek S, Hlavicka J, et al. Comparison of cardiac surgery with left atrial surgical ablation vs. cardiac surgery without atrial ablation in patients with coronary and/or valvular heart disease plus atrial fibrillation: final results of the PRAGUE-12 randomized multicentre study. European Heart Journal. 2012; 33:2644–52. [PubMed: 22930458] * Osmancik P, Budera P, Straka Z, Widimsky P. Predictors of complete arrhythmia free survival in patients undergoing surgical ablation for atrial fibrillation. PRAGUE-12 randomized study sub-analysis. International Journal of Cardiology. 2014; 172(2): 419–22. [PubMed: 24507744] Straka Z, Budera P, Osmancik P, Vanek T, Hulman M, Smid M, et al. Design and rationale of the PRAGUE-12 trial: a large, prospective, randomized, multicenter trial that compares cardiac surgery with left atrial surgical ablation with cardiac surgery without Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22.

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ablation in patients with coronary and/or valvular heart disease plus atrial fibrillation. Clinical Cardiology. 2013; 36:1–5. [PubMed: 23280480] Cherniavsky 2014 {published data only}. Cherniavsky A, Kareva Y, Pak I, Rakhmonov S, Pokushalov E, Romanov A, et al. Assessment of results of surgical treatment for persistent atrial fibrillation during coronary artery bypass grafting using implantable loop recorders. Interactive CardioVascular and Thoracic Surgery. 2014; 18:727–31. [PubMed: 24572769] * Chernyavskiy A, Kareva Y, Pak I, Rakhmonov S, Pokushalov E, Romanov A. Quality of life after surgical ablation of persistent atrial fibrillation: a prospective evaluation. Heart, Lung & Circulation. 2016; 25(4):378–83. Chevalier 2009 {published data only}. Chevalier P, Leizorovicz A, Maureira P, Carteaux JP, Corbineau H, Caus T, et al. Left atrial radiofrequency ablation during mitral valve surgery: a prospective randomized multicentre study (SAFIR). Archives of Cardiovascular Diseases. 2009; 102:769–75. [PubMed: 19944393] * Chevalier P. SAFIR Investigators. Left maze radiofrequency ablation during mitral valve surgery for chronic atrial fibrillation: A randomized multicenter study (SAFIR). Circulation. 2007; 116(16 Suppl):761. de Lima 2004 {published data only}. de Lima GG, Kalil RA, Leiria TL, Hatem DM, Kruse CL, Abrahao R, et al. Randomized study of surgery for patients with permanent atrial fibrillation as a result of mitral valve disease. Annals of Thoracic Surgery. 2004; 77:2089–94. discussion 2094. [PubMed: 15172273] Deneke 2002 {published data only}. Deneke T, Khargi K, Grewe PH, Laczkovics A, von Dryander S, Lawo T, et al. Efficacy of an additional MAZE procedure using cooled-tip radiofrequency ablation in patients with chronic atrial fibrillation and mitral valve disease. A randomized, prospective trial. European Heart Journal. 2002; 23:558–66. [PubMed: 11922646] Doukas 2005 {published data only}. Doukas G, Samani NJ, Alexiou C, Oc M, Chin DT, Stafford PG, et al. Left atrial radiofrequency ablation during mitral valve surgery for continuous atrial fibrillation: a randomized controlled trial. JAMA. 2005; 294:2323–9. [PubMed: 16278360] * Doukas G, Samani NJ, Alexiou C, Chin DT, Stafford PG, Spyt TJ. Left atrial radiofrequency ablation during mitral valve surgery for continuous atrial fibrillation: Results of a prospective randomised clinical trial. Heart. 2005; 91:A1–2. [PubMed: 15831614] Gillinov 2015 {published data only}. Gillinov AM, Argenziano M, Blackstone EH, Iribarne A, DeRose JJ Jr, Ailawadi G, et al. Designing comparative effectiveness trials of surgical ablation for atrial fibrillation: experience of the Cardiothoracic Surgical Trials Network. Journal of Thoracic and Cardiovascular Surgery. 2011; 142:257–64.e2. [PubMed: 21616507] * Gillinov AM, Gelijns AC, Parides MK, DeRose JJ Jr, Moskowitz AJ, Voisine P, et al. Surgical ablation of atrial fibrillation during mitral-valve surgery. New England Journal of Medicine. 2015; 372:1399–409. [PubMed: 25853744] Jessurun 2003 {published data only}. Jessurun ER, van Hemel NM, Defauw JJ, Brutel De La Riviere A, Stofmeel MA, Kelder JC, et al. A randomized study of combining maze surgery for atrial fibrillation with mitral valve surgery. Journal of Cardiovascular Surgery. 2003; 44:9–18. [PubMed: 12627066] Jonsson 2012 {published data only}. Jonsson A, Lehto M, Ahn H, Hermansson U, Linde P, Ahlsson A, et al. Microwave ablation in mitral valve surgery for atrial fibrillation (MAMA). Journal of Atrial Fibrillation. 2012; 5:13–22. Khargi 2001 {published data only}. Khargi K, Deneke T, Haardt H, Lemke B, Grewe P, Muller KM, et al. Saline-irrigated, cooled-tip radiofrequency ablation is an effective technique to perform the maze procedure. Annals of Thoracic Surgery. 2001; 72:S1090–5. [PubMed: 11570381] Knaut 2010 {published data only}. Knaut M, Kolberg S, Brose S, Jung F. Epicardial microwave ablation of permanent atrial fibrillation during a coronary bypass and/or aortic valve operation: Prospective, randomised, controlled, mono-centric study. Applied Cardiopulmonary Pathophysiology: ACP. 2010; 14(4):220–8. Pokushalov 2012 {published data only}. Pokushalov E, Romanov A, Corbucci G, Cherniavsky A, Karaskov A. Benefit of ablation of first diagnosed paroxysmal atrial fibrillation during coronary artery bypass grafting: a pilot study. European Journal of Cardio-Thoracic Surgery. 2012; 41:556–60. [PubMed: 22219409] * Romanov A, Pokushalov E, Cherniavskiy A, Pak I, Kareva Y,


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Karaskov A. Ablation of newly-discovered paroxysmal atrial fibrillation during coronary artery bypass grafting: Necessary? Interactive Cardiovascular and Thoracic Surgery. 2011; 13:S122. Schuetz 2003 {published data only}. Schuetz A, Schulze CJ, Sarvanakis KK, Mair H, Plazer H, Kilger E, et al. Surgical treatment of permanent atrial fibrillation using microwave energy ablation: a prospective randomized clinical trial. European Journal of Cardio-Thoracic Surgery. 2003; 24:475–80. discussion 480. [PubMed: 14500062] Srivastava 2008 {published data only}. Srivastava V, Kumar S, Javali S, Rajesh TR, Pai V, Khandekar J, et al. Efficacy of three different ablative procedures to treat atrial fibrillation in patients with valvular heart disease: a randomised trial. Heart, Lung & Circulation. 2008; 17:232–40. van Breugel 2010 {published data only}. Van Breugel HN, Nieman FH, Accord RE, Van Mastrigt GA, Nijs JF, Severens JL, et al. A prospective randomized multicenter comparison on health-related quality of life: the value of add-on arrhythmia surgery in patients with paroxysmal, permanent or persistent atrial fibrillation undergoing valvular and/or coronary bypass surgery. Journal of Cardiovascular Electrophysiology. 2010; 21:511–20. [PubMed: 19925605] * van Breugel NH, Bidar E, Essers BA, Nieman FH, Accord RE, Severens JL, et al. Cost-effectiveness of ablation surgery in patients with atrial fibrillation undergoing cardiac surgery. Interactive Cardiovascular and Thoracic Surgery. 2011; 12:394–8. [PubMed: 21148666] Vasconcelos 2004 {published data only}. Vasconcelos JT, Scanavacca MI, Sampaio RO, Grinberg M, Sosa EA, Oliveira SA. Surgical treatment of atrial fibrillation through isolation of the left atrial posterior wall in patients with chronic rheumatic mitral valve disease. A randomized study with control group. Arquivos Brasileiros de Cardiologia. 2004; 83(3):211–8. 203–10. [PubMed: 15375469] von Oppell 2009 {published data only}. von Oppell UO, Masani N, O’Callaghan P, Wheeler R, Dimitrakakis G, Schiffelers S. Mitral valve surgery plus concomitant atrial fibrillation ablation is superior to mitral valve surgery alone with an intensive rhythm control strategy. European Journal of Cardio-Thoracic Surgery. 2009; 35:641–50. [PubMed: 19233678] Wang 2014 {published data only}. Wang X, Wang X, Song Y, Hu S, Wang W. Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease. International Journal of Cardiology. 2014; 174:497–502. [PubMed: 24820759] * Xin W. Efficiency of radiofrequency ablation for surgical treatment of chronic atrial fibrillation in rheumatic valvular disease. Circulation. 2012; 126(21 Suppl):A15503.

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References to studies excluded from this review

Author Manuscript

Ailawadi 2011 {published data only}. Ailawadi G, Gerdisch MW, Harvey RL, Hooker RL, Damiano RJ Jr, Salamon T, et al. Exclusion of the left atrial appendage with a novel device: early results of a multicenter trial. Journal of Thoracic and Cardiovascular Surgery. 2011; 142(5):1002–9. 1009.e1. [PubMed: 21906756] Al-Atassi 2014 {published data only}. Al-Atassi T, Toeg H, Malas T, Lam BK. Mapping and ablation of autonomic ganglia in prevention of postoperative atrial fibrillation in coronary surgery: MAAPPAFS atrial fibrillation randomized controlled pilot study. Canadian Journal of Cardiology. 2014; 30(10):1202–7. [PubMed: 25262862] Al Halabi 2015 {published data only}. Al Halabi S, Qintar M, Alraies MC, Cantillon D, Tarakji K, Kanj M, et al. Ablation of atrial fibrillation in heart failure patients: A meta-analysis of randomized controlled trials. Journal of the American College of Cardiology. 2015; 65(10 Suppl):A415. Al-Khatib 2014 {published data only}. Al-Khatib SM, Allen LaPointe NM, Chatterjee R, Crowley MJ, Dupre ME, Kong DF, et al. Rate- and rhythm-control therapies in patients with atrial fibrillation: a systematic review. Annals of Internal Medicine. 2014; 160(11):760–73. [PubMed: 24887617] Assasi 2012 {published data only}. Assasi, N.; Blackhouse, G.; Xie, F.; Gaebel, K.; Robertson, D.; Hopkins, R., et al. CADTH Technology Overviews. Vol. 2. Canadian Agency for Drugs and Technologies in Health (CADTH); 2012. Ablation procedures for rhythm control in patients with atrial fibrillation: clinical and cost-effectiveness analyses; p. e2101


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Basu 2012 {published data only}. Basu S, Nagendran M, Maruthappu M. How effective is bipolar radiofrequency ablation for atrial fibrillation during concomitant cardiac surgery? Interactive Cardiovascular and Thoracic Surgery. 2012; 15:741–8. [PubMed: 22815321] Biancari 2010 {published data only}. Biancari F, Mahar MA. Meta-analysis of randomized trials on the efficacy of posterior pericardiotomy in preventing atrial fibrillation after coronary artery bypass surgery. Journal of Thoracic and Cardiovascular Surgery. 2010; 139:1158–61. [PubMed: 19691996] Bockeria 2011 {published data only}. Bockeria LA, Bockeria OL, Zavarina AY, Mordvinova AS. The early recurrence is a predictor of late failure in surgical ablation of atrial fibrillation. Interactive Cardiovascular and Thoracic Surgery. 2011; 12(5):686. [PubMed: 21555434] Breda 2008 {published data only}. Breda JR, Breda AS, Freitas AC, Meneghini A, Tavares CM, Abreu LC, et al. Effect of ventral cardiac denervation in the incidence of atrial fibrillation after coronary artery bypass graft surgery. Revista Brasileira de Cirurgia Cardiovascular. 2008; 23:204–8. [PubMed: 18820783] Budera 2015 {published data only}. Budera P, Osmancik P, Straka Z. Having sinus rhythm definitely pays off. PRAGUE-12 randomized study sub-analysis. European Heart Journal. 2015; 36:743. [PubMed: 24835485] Camm 2011 {published data only}. Camm CF, Nagendran M, Xiu PY, Maruthappu M. How effective is cryoablation for atrial fibrillation during concomitant cardiac surgery? Interactive Cardiovascular and Thoracic Surgery. 2011; 13:410–4. [PubMed: 21791522] CEDIT 2006 {published data only}. Comite d’Evaluation et de Diffusion des Innovations Technologiques (CEDIT). New techniques for the surgical treatment of atrial fibrillation (Surgifrost(R), Epicor(R)) - systematic review, expert panel. Paris: Comite d’Evaluation et de Diffusion des Innovations Technologiques (CEDIT); 2006. Cheng 2010 {published data only}. Cheng DC, Ad N, Martin J, Berglin EE, Chang BC, Doukas G, et al. Surgical ablation for atrial fibrillation in cardiac surgery: a meta-analysis and systematic review. Innovations. 2010; 5(2):84–96. [PubMed: 22437354] CNHTA 2010 {published data only}. Committee for New Health Technology Assessment (CNHTA). [Surgical ablation of atrial fibrillation with HIFU]. Seoul: Committee for New Health Technology Assessment (CNHTA); 2010. Damiano 2003 {published data only}. Damiano RJ, McCarthy PM, Gillinov AM, Ryan WH, Moon MR, Mack MJ, et al. Prospective multicenter clinical trial of surgical pulmonary vein isolation for the treatment of atrial fibrillation. Journal of the American College of Cardiology. 2003; 41(6 Suppl):498A. DECIT-CGATS 2009 {published data only}. Department of Science and Technology - Brazilian Health Technology Assessment General Coordination (DECIT-CGATS). Department of Science and Technology - Brazilian Health Technology Assessment General Coordination. Department of Science and Technology – Brazilian Health Technology Assessment General Coordination (DECIT–CGATS); 2009. Rapid HTA on the use of radiofrequency ablation in the surgical treatment of atrial fibrillation. Deneke 2001 {published data only}. Deneke T, Khargi K, Grewe P, Schick E, Lawo T, Von Dryander S, et al. Treatment of chronic atrial fibrillation with the Cox-MAZE procedure using radiofrequency ablation: A prospective, randomized study. Herzschrittmachertherapie und Elektrophysiologie. 2001; 12(Suppl):135–6. Deneke 2002a {published data only}. Deneke T, Bochum B, Khargi K, Grewe PH, Kuschkowitz F, Lawo T, et al. Left atrial versus biatrial antiarrhythmic surgery to treat chronic permanent atrial fibrillation: A prospective trial in 84 patients with 6 months follow-up. Circulation. 2002; 106:323. Doulkas 2004 {published data only}. Doulkas G, Stafford P, Chin D, Samani N, Spyt T. Pulmonary vein isolation by radiofrequency ablation during mitral valve surgery reduces chronic atrial fibrillation: a randomized prospective trial. Circulation. 2004; 110(17):692. [PubMed: 15262839] Dunning 2013 {published data only}. Dunning J, Nagendran M, Alfieri OR, Elia S, Kappetein AP, Lockowandt U, et al. Guideline for the surgical treatment of atrial fibrillation. European Journal of Cardio-Thoracic Surgery. 2013; 44:777–91. [PubMed: 23956274]


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ECRI 2004 {published data only}. ECRI. Maze Surgery for Medically Refractory Atrial fFbrillation. Plymouth Meeting, PA: ECRI; 2004. p. 83 Emmert 2014 {published data only}. Emmert MY, Puippe G, Baumuller S, Alkadhi H, Landmesser U, Plass A, et al. Safe, effective and durable epicardial left atrial appendage clip occlusion in patients with atrial fibrillation undergoing cardiac surgery: first long-term results from a prospective device trial. European Journal of Cardio-Thoracic Surgery. 2014; 45:126–31. [PubMed: 23657550] Hazel 2004 {published data only}. Hazel, SJ.; Edwards, J.; Paterson, H. Australian Safety and Efficacy Register of New Interventional Procedures-Surgical (ASERNIP-S), Report No. 38. Royal Australasian College of Surgeons, Australian Safety and Efficacy Register of New Interventional Procedures (ASERNIP) – Surgical; 2004. Systematic review of intraoperative ablation for the treatment of atrial fibrillation. Healey 2005 {published data only}. Healey JS, Crystal E, Lamy A, Teoh K, Semelhago L, Hohnloser SH, et al. Left Atrial Appendage Occlusion Study (LAAOS): results of a randomized controlled pilot study of left atrial appendage occlusion during coronary bypass surgery in patients at risk for stroke. American Heart Journal. 2005; 150:288–93. [PubMed: 16086933] Hornero 2001 {published data only}. Hornero Sos F, Atienza Fernandez F, Montero Argudo JA, Gil Albarov O, Garcia Fuster R, Paya Serrano R, et al. Partial left atriectomy in the treatment of atrial fibrillation associated with mitral valve disease. Revista Española de Cardiología. 2001; 54:703– 8. [PubMed: 11412776] Hornero 2003 {published data only}. Hornero Sos F, Montero Argudo JA, Canovas Lopez S, Gil Alabarova O, Garcia Fuster R, Perez Bosca JL, et al. Anatomic atrial remodeling after mitral valve surgery in permanent atrial fibrillation. Revista Española de Cardiología. 2003; 56:674–81. [PubMed: 12855150] Je 2015 {published data only}. Je HG, Shuman DJ, Ad N. A systematic review of minimally invasive surgical treatment for atrial fibrillation: a comparison of the Cox-Maze procedure, beating-heart epicardial ablation, and the hybrid procedure on safety and efficacy. European Journal of CardioThoracic Surgery. 2015; 48(4):531–40. [PubMed: 25567961] Kearney 2014 {published data only}. Kearney K, Stephenson R, Phan K, Chan WY, Huang MY, Yan TD. A systematic review of surgical ablation versus catheter ablation for atrial fibrillation. Annals of Cardiothoracic Surgery. 2014; 3:15–29. [PubMed: 24516794] Khargi 2005 {published data only}. Khargi K, Hutten BA, Lemke B, Deneke T. Surgical treatment of atrial fibrillation; a systematic review. European Journal of Cardio-Thoracic Surgery. 2005; 27:258–65. [PubMed: 15691679] Kong 2009 {published data only}. Kong MH, Lopes RD, Piccini JP, Hasselblad V, Bahnson TD, AlKhatib SM. Surgical maze procedure as a treatment for atrial fibrillation: A meta-analysis of randomized controlled trials. Journal of the American College of Cardiology. 2009; 53:A118. Kong 2010 {published data only}. Kong MH, Lopes RD, Piccini JP, Hasselblad V, Bahnson TD, AlKhatib SM. Surgical Maze procedure as a treatment for atrial fibrillation: a meta-analysis of randomized controlled trials. Cardiovascular Therapeutics. 2010; 28(5):311–26. [PubMed: 20370795] Krul 2013 {published data only}. Krul SP, Driessen AH, Zwinderman AH, Boven WJ, Wilde AA, Bakker JM, et al. Navigating the mini-maze: systematic review of the first results and progress of minimally-invasive surgery in the treatment of atrial fibrillation. International Journal of Cardiology. 2013; 166:132–40. [PubMed: 22078990] Lebedev 2008 {published data only}. Lebedev D, Mikhaylov E. Effectiveness of different ablation methods for paroxysmal atrial fibrillation in randomized study. Circulation. 2008; 118:E404. Lemke 2000 {published data only}. Lemke B, Khargi K, Deneke T, Grewe P, Lawo T, Schick E, et al. Restoration of sinus rhythmus in patients with chronic atrial fibrillation and mitral valve defects using the Cox-Maze-3-operation: A prospective, randomised study. Zeitschrift fur Kardiologie. 2000; 89(Suppl 5):89. Lins 2010 {published data only}. Lins RM, de Lima RC, Silva FP, Menezes AM, Salerno PR, Thé EC, et al. Treatment of atrial fibrillation using ultrasonic cardiac ablation, during valvular heart surgery. Revista Brasileira de Cirurgia Cardiovascular. 2010; 25(3):326–32. [PubMed: 21103740]


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Liu 2010 {published data only}. Liu X, Tan HW, Wang XH, Shi HF, Li YZ, Li F, et al. Efficacy of catheter ablation and surgical CryoMaze procedure in patients with long-lasting persistent atrial fibrillation and rheumatic heart disease: a randomized trial. European Heart Journal. 2010; 31(21):2633–41. [PubMed: 20573636] MacDonald 2012 {published data only}. MacDonald DR, Maruthappu M, Nagendran M. How effective is microwave ablation for atrial fibrillation during concomitant cardiac surgery? Interactive Cardiovascular and Thoracic Surgery. 2012; 15(1):122–7. [PubMed: 22510269] Molina 2008 {published data only}. Molina Linde, JM.; Villegas Portero, R.; Lacalle Remigio, JR.; Porras Martin, C.; Perez Duarte, E.; Gonzalez Calle, A., et al. Standards for health technologies appropriateness: Indications of intra-operative ablation in patients with atrial fibrillation. Development of criteria for appropriateness. Seville: Andalusian Agency for Health Technology Assessment (AETSA); 2008. p. 1-115. Nagpal 2009 {published data only}. Nagpal AD, Torracca L, Fumero A, Denti P, Cioni M, Alfieri O. Concurrent prophylactic left atrial appendage exclusion: results from a randomized controlled trial pilot study. European Journal of Cardiothoracic Surgery. 2009; 36:553–7. [PubMed: 19473853] NCT00157807 {unpublished data only}. NCT00157807. [accessed 7 May 2016] Clinical and economic consequences of left atrial bipolar radiofrequency ablation of persistent and permanent AF during cardiac surgery. clinicaltrials.gov/ct2/show/NCT00157807 NICE 2005 {published data only}. National Institute for Clinical Excellence. NICE interventional procedure guidance, Report No. IPG121. London: National Institute for Clinical Excellence (NICE); 2005. Radiofrequency ablation for atrial fibrillation in association with other cardiac surgery; p. 245 NICE 2005a {published data only}. National Institute for Clinical Excellence. NICE interventional procedure guidance, Report No. IPG122. London: National Institute for Clinical Excellence (NICE); 2005. Microwave ablation for atrial fibrillation in association with other cardiac surgery; p. 266 NICE 2005b {published data only}. National Institute for Clinical Excellence. NICE interventional procedure guidance, Report No. IPG123. London: National Institute for Clinical Excellence (NICE); 2005. Cryoablation for atrial fibrillation in association with other cardiac surgery; p. 271 NICE 2006 {published data only}. National Institute for Health and Clinical Excellence. NICE interventional procedure guidance, Report No. IPG184. London: National Institute for Health and Clinical Excellence (NICE); 2006. High-intensity focused ultrasound for atrial fibrillation in association with other cardiac surgery; p. 312 NICE 2010 {published data only}. National Institute of Health and Care Excellence. NICE interventional procedure guidance, Report No. IPG286. Seoul: Committee for New Health Technology Assessment (CNHTA); 2010. Thoracoscopic epicardial radiofrequency ablation for atrial fibrillation; p. IP 716 Ninet 2005 {published data only}. Ninet J, Roques X, Seitelberger R, Deville C, Pomar JL, Robin J, et al. Surgical ablation of atrial fibrillation with off-pump, epicardial, high-intensity focused ultrasound: results of a multicenter trial. Journal of Thoracic and Cardiovascular Surgery. 2005; 130(3):803–9. [PubMed: 16153932] Ontario 2006 {published data only}. Health Quality Ontario. Ontario Health Technology Assessment Series. Vol. 6. Toronto: Medical Advisory Secretariat, Ontario Ministry of Health and Long– Term Care (MAS); 2006. Ablation for atrial fibrillation: an evidence-based analysis; p. 1-63. Padanilam 2015 {published data only}. Padanilam BJ, Foreman J, Prystowsky EN. Patients with minimal atrial fibrillation events should not undergo concomitant atrial ablation during open heart procedures. Cardiac Electrophysiology Clinics. 2015; 7(3):395–401. [PubMed: 26304518] Passage 2010 {published data only}. Passage J, Borger MA, Seeburger J, Rastan A, Walther T, Doll N, et al. Cryoablation for the treatment of atrial fibrillation in patients undergoing minimally invasive mitral valve surgery Technique and recent results. Aortic Root Surgery: The Biological Solution. 2010:291–301. Phan 2014 {published data only}. Phan K, Xie A, La Meir M, Black D, Yan TD. Surgical ablation for treatment of atrial fibrillation in cardiac surgery: A cumulative meta-analysis of randomised controlled trials. Heart. 2014; 100:722–30. [PubMed: 24650881]


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Phan 2014a {published data only}. Phan K, Xie A, Tian DH, Shaikhrezai K, Yan TD. Systematic review and meta-analysis of surgical ablation for atrial fibrillation during mitral valve surgery. Annals of Cardiothoracic Surgery. 2014; 3:3–14. [PubMed: 24516793] Phan 2015 {published data only}. Phan K, Xie A, Kumar N, Wong S, Medi C, La Meir M, et al. Comparing energy sources for surgical ablation of atrial fibrillation: a Bayesian network metaanalysis of randomized, controlled trials. European Journal of Cardio-Thoracic Surgery. 2015; 48(2):201–11. [PubMed: 25391388] Pires 2010 {published data only}. Pires LM, Leiria TL, de Lima GG, Kruse ML, Nesralla IA, Kalil RA. Comparison of surgical cut and sew versus radiofrequency pulmonary veins isolation for chronic permanent atrial fibrillation: a randomized study. Pacing and Clinical Electrophysiology: PACE. 2010; 33:1249–57. [PubMed: 20546155] Quenneville 2009 {published data only}. Quenneville SP, Xie X, Brophy JM. The cost-effectiveness of Maze procedures using ablation techniques at the time of mitral valve surgery. International Journal of Technology Assessment in Health Care. 2009; 25:485–96. [PubMed: 19818194] Reents 2014 {published data only}. Reents W, Diegeler A, Babin-Ebell J, Boning A, Whitlock RP. Rationale and trial design of the Left Atrial Appendage Occlusion Study (LAAOS III). Thoracic and Cardiovascular Surgeon. 2014; 62:45–54. Reston 2005 {published data only}. Reston JT, Shuhaiber JH. Meta-analysis of clinical outcomes of maze-related surgical procedures for medically refractory atrial fibrillation. European Journal of Cardio-Thoracic Surgery. 2005; 28:724–30. [PubMed: 16143540] Senatore 2001 {published data only}. Senatore G, Carreras G, Taglieri C, Giordano B, Ingignoli B, Mazza A, et al. Intraoperative radiofrequency catheter ablation of atrial fibrillation: Randomized study. Europace. 2001:579–82. Tsai 2015 {published data only}. Tsai YC, Phan K, Munkholm-Larsen S, Tian DH, La Meir M, Yan TD. Surgical left atrial appendage occlusion during cardiac surgery for patients with atrial fibrillation: a meta-analysis. European Journal of Cardio-Thoracic Surgery. 2015; 47:847–54. [PubMed: 25064051] Vicol 2005 {published data only}. Clinical and economic consequences of left atrial bipolar radiofrequency ablation of persistent and permanent atrial fibrillation during cardiac surgery. Clinicaltrials.gov: NCT00157807. Whitlock 2013 {published data only}. Whitlock RP, Vincent J, Blackall MH, Hirsh J, Fremes S, Novick R, et al. Left atrial appendage occlusion study II (LAAOS II). Canadian Journal of Cardiology. 2013; 29:1443–7. [PubMed: 24054920] Wong 2006a {published data only}. Wong JW, Mak KH. Impact of maze and concomitant mitral valve surgery on clinical outcomes. Annals of Thoracic Surgery. 2006; 82:1938–47. [PubMed: 17062288] Zhang 2012 {published data only}. Zhang GX, Han L, Zhong K, Li L, Lu FL, Wang C, et al. Double atrial ablation with monopolar irrigated radiofrequecy for atrial fibrillation during minimally invasive mitral valve surgery via right thoracotomy: A clinical controlled study. [Chinese]. Academic Journal of Second Military Medical University. 2012; 33(11):1212–6.

References to studies awaiting assessment

Author Manuscript

ChiCTR-TRC-07003039 {unpublished data only}. ChiCTR-TRC-07003039. [accessed 6 May 2016] A prospective single-center clinical trial of radiofrequency ablation maze procedure in surgical treatment of rheumatic heart valve disease. www.chictr.org.cn/showprojen.aspx?proj+6518 NCT00735722 {unpublished data only}. NCT00735722. [accessed 6 May 2016] A(f )MAZE-CABG Study (AFMAZE-CABG). clinicaltrials.gov/ct2/show/NCT00735722 NCT01791218 {unpublished data only}. NCT01791218. [accessed 6 May 2016] Surgical pulmonary vein isolation efficiency study (FIN-PVI). clinicaltrials.gov/ct2/show/NCT01791218


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References to ongoing studies

Author Manuscript

ISRCTN14454361 {unpublished data only}. ISRCTN14454361. [accessed 6 May 2016] A randomised controlled trial to investigate the biochemical and myocardial effects of ablation for AF at concomitant elective cardiac surgery with two different methods, freezing versus heating (RAFTMSR). www.isrctn.com/ISRCTN14454361 ISRCTN82731440 {unpublished data only}. ISRCTN82731440. [accessed 6 May 2016] A randomised controlled trial to investigate the clinical and cost effectiveness of adding an ablation devicebased maze procedure as a routine adjunct to elective cardiac surgery for patients with preexisting atrial fibrillation (AMAZE). www.isrctn.com/ISRCTN82731440. Health Technology Assessment NCT01360918 {unpublished data only}. NCT01360918. [accessed 6 May 2016] Concomitant epicardial pulmonary vein isolation in patients with AF undergoing elective cardiac surgery (CONTROL-AF). clinicaltrials.gov/ct2/show/NCT01360918 NCT01649544 {unpublished data only}. NCT01649544. [accessed 6 May 2016] Comparison of treatment of atrial fibrillation (AF) between surgical ultrasonic technology or drug therapy for patients with AF requiring mitral valve surgery (EPICAF). https://clinicaltrials.gov/ct2/show/ NCT01649544 UMIN000016129 {unpublished data only}. UMIN000016129. [accessed 6 May 2016] Surgical Ablation for Non Mitral Operation: Randomized multi-Institutional Trial and optimiZation (SANMORITZ study). upload.umin.ac.jp/cgi-open-bin/icdr.e/ctr.view.cgi?recptno+R000018712

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APPENDICES Appendix 1. Search strategies Cochrane Library (CDSR, CENTRAL, DARE, HTA) ID Search


#1

MeSH descriptor: [Cardiac Surgical Procedures] explode all trees

#2

MeSH descriptor: [Atrial Fibrillation] this term only

#3

MeSH descriptor: [Atrial Flutter] this term only

#4

MeSH descriptor: [Tachycardia, Ectopic Atrial] this term only

#5

((atrial or atrium or auricular) near/2 (fibrillat* or flutter*) near/10 (surgery or surgeries or surgical or procedure* or operat*)): ti,ab,kw

#6

((atrial or atrium or auricular) near/2 (tachycardia* or tachyarrhythmia*) near/10 (surgery or surgeries or surgical or procedure* or operat*)):ti,ab,kw

#7

#2 or #3 or #4

#8

#1 and #7

#9

#5 or #6 or #8

#10

MeSH descriptor: [Atrial Fibrillation] this term only

#11

((atrial or atrium or auricular) near/2 (fibrillat* or flutter*)):ti,ab,kw

#12

MeSH descriptor: [Atrial Flutter] this term only

#13

MeSH descriptor: [Tachycardia, Ectopic Atrial] this term only

#14

((atrial or atrium or auricular) near/2 (tachycardia* or tachyarrhythmia*)):ti,ab,kw

#15

#10 or #11 or #12 or #13 or #14

#16

MeSH descriptor: [Ablation Techniques] explode all trees

#17

ablat*:ti,ab,kw

#18

cauteriz*:ti,ab,kw

#19

(cryomaze or cryosurg* or cryoablat*):ti,ab,kw

#20

“high intensity focused ultrasound”:ti,ab,kw

#21

maze:ti,ab,kw

#22

(cut next/2 sew):ti,ab,kw

#23

“vagal denervation”:ti,ab,kw

#24

(radiofrequenc* or RF):ti,ab,kw

#25

microwave*:ti,ab,kw


Huffman et al.

Page 30

Author Manuscript

#26

(“pulmonary vein” next/3 isolat*):ti,ab,kw

#27

#16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26

#28

#15 and #27

#29

#9 or #28

Ovid MEDLINE(R) 1946 to March Week 4 2016 and Ovid MEDLINE(R) InProcess & Other Non-Indexed Citations March 30, 2016


1.

exp Cardiac Surgical Procedures/

2.

Atrial Fibrillation/

3.

Atrial Flutter/

4.

Tachycardia, Ectopic Atrial/

5.

((atrial or atrium or auricular) adj2 (fibrillat* or flutter*) adj10 (surgery or surgeries or surgical or procedure* or operat*)).tw.

6.

((atrial or atrium or auricular) adj2 (tachycardia* or tachyarrhythmia*) adj10 (surgery or surgeries or surgical or procedure* or operat*)).tw.

7.

2 or 3 or 4

8.

1 and 7

9.

5 or 6 or 8

10.

Atrial Fibrillation/

11.

((atrial or atrium or auricular) adj2 (fibrillat* or flutter*)).tw.

12.

Atrial Flutter/

13.

Tachycardia, Ectopic Atrial/

14.

((atrial or atrium or auricular) adj2 (tachycardia* or tachyarrhythmia*)).tw.

15.

or/10–14

16.

exp Ablation Techniques/

17.

ablat*.tw.

18.

cauteriz*.tw.

19.

(cryomaze or cryosurg* or cryoablat*).tw.

20.

high intensity focused ultrasound.tw.

21.

maze.tw.

22.

(cut adj2 sew).tw.

23.

vagal denervation.tw.


Huffman et al.

Page 31


24.

(radiofrequenc* or RF).tw.

25.

microwave*.tw.

26.

(pulmonary vein* adj3 isolat*).tw.

27.

or/16–26

28.

15 and 27

29.

9 or 28

30.

Randomised controlled trial.pt.

31.

controlled clinical trial.pt.

32.

Randomised.ab.

33.

placebo.ab.

34.

clinical trials as topic.sh.

35.

randomly.ab.

36.

trial.ti.

37.

30 or 31 or 32 or 33 or 34 or 35 or 36

38.

exp animals/ not humans.sh.

39.

37 not 38

40.

29 and 39

41.

limit 40 to yr=“1987 -Current”

Author Manuscript

Embase 1974-present; Embase Classic 1947–1973; MEDLINE 1966-present (embase.com)

Author Manuscript

#38

#37 AND [1987–2015]/py

#37

#35 NOT #36

#36

’animal’/exp OR ’nonhuman’/exp NOT ’human’/exp

#35

#33 AND #34

#34

random*:ab,ti OR placebo* OR (double NEXT/1 blind*):ab,ti

#33

#9 OR #32

#32

#15 AND #31

#31

#16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30

#30

(’pulmonary vein’ NEXT/3 isolat*):ab,ti

#29

microwave*:ab,ti


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Page 32


#28

radiofrequenc*:ab,ti OR rf:ab,ti

#27

’vagal denervation’:ab,ti

#26

(cut NEXT/2 sew):ab,ti

#25

maze:ab,ti

#24

cauteriz*:ab,ti

#23

’cauterization’/de

#22

’high intensity focused ultrasound’:ab,ti

#21

’high intensity focused ultrasound’/de

#20

cryomaze:ab,ti OR cryosurg*:ab,ti OR cryoablat*:ab,ti

#19

’cryoablation’/de

#18

’cryosurgery’/de

#17

ablat*:ab,ti

#16

’ablation therapy’/de

#15

#10 OR #11 OR #12 OR #13 OR #14

#14

((atrial OR atrium OR auricular) NEXT/2 (tachycardia* OR tachyarrhythmia*)):ab,ti

#13

’ectopic atrial tachycardia’/de

#12

’heart atrium flutter’/de

#11

((atrial OR atrium OR auricular) NEXT/2 (fibrillat* OR flutter*)):ab,ti

#10

’atrial fibrillation’/exp

#9

#5 OR #6 OR #8

#8

#1 AND #7

#7

#2 OR #3 OR #4

#6

((atrial OR atrium OR auricular) NEXT/2 (tachycardia* OR tachyarrhythmia*) NEXT/10 (surgery OR surgeries OR surgical OR procedure* OR operat*)):ab,ti

#5

((atrial OR atrium OR auricular) NEXT/2 (fibrillat* OR flutter*) NEXT/10 (surgery OR surgeries OR surgical OR procedure* OR operat*)):ab,ti

#4

’ectopic atrial tachycardia’/de

#3

’heart atrium flutter’/de

#2

’atrial fibrillation’/exp

#1

’heart surgery’/exp


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Author Manuscript

Conference Proceedings Citation Index- Science (CPCI-S) --1990-present (Web of Science)

Author Manuscript

#7

#6 AND #5

#6

TS=(random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross-over* or group*)

#5

#4 OR #1

#4

#3 AND #2

#3

TS=(ablat* or cauteriz* or cryomaze or cryosurg* or cryoablat* or “high intensity focused ultrasound” or maze or (cut NEAR/2 sew) or “vagal denervation” or radiofrequenc* or RF or microwave* or (“pulmonary vein” NEAR/3 isolat*))

#2

TS=((atrial or atrium or auricular) NEAR/2 (fibrillat* or flutter* or tachycardia* or tachyarrhythmia*))

#1

TS=((atrial or atrium or auricular) NEAR/2 (fibrillat* or flutter* or tachycardia* or tachyarrhythmia*) NEAR/10 (surgery or surgeries or surgical or procedure* or operat*))

Clinical Trials Registers ClinicalTrials.gov https://clinicaltrials.gov/ct2/home

Author Manuscript

Advanced search Search Terms: surgery OR maze OR cox OR cryomaze OR cryosurgery OR microwave Conditions: “atrial fibrillation” Study Type: Interventional Studies April 1, 2015-227 Studies found https://clinicaltrials.gov/ct2/results/refine?term=surgery+OR+maze+OR+cox+OR +cryomaze+OR+cryosurgery+OR+microwave&type=Intr&cond=%22atrial+fibrillation%22

Author Manuscript

World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) http://apps.who.int/trialsearch/ Advanced search Condition: atrial fibrillation Intervention: surgery OR maze OR cox OR cryomaze OR cryosurgery OR microwave


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Recruitment status: ALL

Author Manuscript

April 1, 2015-87 records for 85 trials found

CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID] Abreu Filho 2005


Methods

Randomiseded controlled, parallel group trial

Participants

70 participants with permanent AF, pre-existing for >1 year, rheumatic mitral valve disease requiring mitral valve surgery from Sao Paulo, Brazil Exclusion criteria: none reported Intervention (n = 42): mean (SD) age: 55.4 (12.8) years, 67% women, 100% rheumatic valve disease, 100% permanent AF, mean duration of AF 66 months, mean ejection fraction 66%, 31% mitral valve repair, 69% mitral valve replacement, 26% concomitant tricuspid valve surgery, mean (SD) cardiopulmonary bypass time 107.2 (21.1) minutes; mean (SD) aortic cross-clamp time 67.5 (13.5) minutes Comparator (n = 28): mean (SD) age: 50.7 (9.7) years, 57% women, 100% rheumatic valve disease, 100% permanent AF, mean duration of AF 44 months, mean ejection fraction 63%, 4% mitral valve repair, 97% mitral valve replacement, 28% concomitant tricuspid valve surgery, mean (SD) cardiopulmonary bypass time 78.2 (24.4) minutes; mean (SD) aortic cross-clamp time 47.1 (15.8) minutes

Interventions

Intervention: valve surgery + bi-atrial maze with radiofrequency generator and unipolar ablation catheter (LA, RA, bilateral PVI, LAA) via Saline-Irrigated Cooled-tip Radiofrequency Ablation (SICTRA) System (Cardioblate, Medtronic Inc, Minneapolis, MN) Comparison: valve surgery (including LAA excision) + usual care

Outcomes

Not specified in methods or protocol; outcomes reported include: rhythm at 12 months, all-cause mortality, adverse events Mean (SD) follow-up: 13.8 (3.4) months in intervention, 11.5 (7.3) months in control Arrhythmia monitoring during follow-up: clinical evaluation and 12-lead ECG and 24-hour Holter at 3, 6, 12 months

Notes

Usual care included: prophylactic anti-arrhythmic drug administered routinely (IV amiodarone), discharged with amiodarone 200 mg/d and routine amiodarone 200 mg/d for 3–6 months, tapered per clinician discretion and only if 24-hour ECG confirmed sinus rhythm Funding: not reported

Risk of bias

Author Manuscript

Bias

Authors’ judgement

Support for judgement


Unclear risk

Methods of randomisation not reported


Unclear risk

Methods of allocation concealment not reported

Blinding of participants and personnel (performance bias) All outcomes

High risk

No mention of blinding; personnel likely unblinded given the nature of the intervention

Blinding of outcome assessment (detection bias) All outcomes

Unclear risk

Not reported; Holter monitoring used for outcome assessment

Incomplete outcome data (attrition bias) All outcomes

Low risk

“The 12-month follow-up was completed in all surviving patients of both groups.”


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Author Manuscript


Unclear risk

No protocol available

Other bias

High risk

Small-study bias

Akpinar 2003

Author Manuscript

Methods

Randomised controlled, parallel group (1:1) trial

Participants

67 participants with a history of persistent AF > 6 months in patients undergoing minimally invasive mitral valve surgery in Istanbul, Turkey Exclusion criteria: severe chest wall deformities (pectus excavatum), significant coronary artery disease, aortic valve insufficiency, lung adhesions and patients with iliac artery disease Intervention (n = 33): mean (SD) age: 53 (10) years, 61% women, 55% rheumatic valvular disease, 100% “chronic AF” consistent with longstanding persistent AF, mean duration of AF 20 months, mean ejection fraction 55%, 36% mitral valve repair, 64% mitral valve replacement, 21% concomitant tricuspid valve surgery, mean (SD) cardiopulmonary bypass time 140.5 (34.3) minutes; mean (SD) aortic cross-clamp time 88.5 (13.4) minutes Comparator (n = 34): mean (SD) age: 50 (8) years, 74% women, 59% rheumatic valvular disease, 100% “chronic AF” consistent with longstanding consistent, mean duration of AF 22 months, mean ejection fraction 55%, 38% mitral valve repair, 62% mitral valve replacement, 27% concomitant tricuspid valve surgery, mean (SD) cardiopulmonary bypass time 128.3 (28.3) minutes; mean (SD) aortic cross-clamp time 78.9 (9.4) minutes

Interventions

Intervention: valve surgery + modified maze with unipolar radiofrequency (left atrial, bilateral pulmonary vein isolation, and left atrial appendage ligation for all; bi-atrial performed only if right atrium opened for tricuspid valve evaluation of atrial septal defect repair) using Cardioblate system (Medtronic Inc, Minneapolis, MN) Comparator: valve surgery + anti-arrhythmic drug therapy (amiodarone) for 12 months

Outcomes

Not specified in methods or protocol; outcomes reported include: rhythm at 12 months, all-cause mortality, CVD mortality, CVD events, adverse events Mean follow-up: 10 months (95% CI 9.18 to 10.8) Arrhythmia monitoring during follow-up: clinical evaluation and 12-lead ECG at 6, 12, and >12 months

Notes

Usual care included: amiodarone administered in the first 3 months then gradually discontinued thereafter Funding: not reported

Risk of bias


Bias




Unclear risk



Unclear risk



High risk



High risk

Relied upon 12-lead ECG for outcome assessment; blinding of outcome assessors not reported


Low risk

All participants analysed for final outcomes


Unclear risk


Other bias

High risk

Small-study bias


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Author Manuscript

Albrecht 2009

Author Manuscript

Methods

Randomised controlled, parallel group (1:1:1) trial

Participants

60 participants with permanent AF and fulfilling clinical and haemodynamic criteria for elective mitral valve correction in Brazil Exclusion criteria: permanent AF < 6 months, age 79 years, LVEF < 20%, pregnant, reoperations, presence of intrapericardial adhesions, reference from a cardiologist to any AF correction technique, patient non-acceptance Intervention groups 1 (SPVI; n = 20): mean (SD) age: 55.1(9.2) years, 70% women, 80% rheumatic valvular disease, 100% permanent AF (mean duration 32 months), mean ejection fraction 62%, 60% mitral valve repair, 40% mitral valve replacement, 25% “associated” surgery, mean (SD) cardiopulmonary bypass time 99.9 (23.8) minutes; mean (SD) aortic cross-clamp time 74.8 (19.2) minutes Intervention group 2 (maze; n = 20): mean (SD) age: 51.7 (12.4) years, 75% women, 75% rheumatic valvular disease, 100% permanent AF, mean duration of AF 35 months, mean ejection fraction 64%, 55% mitral valve repair, 45% mitral valve replacement, 10% “associated” surgery, mean (SD) cardiopulmonary bypass time 123 (21) minutes; mean (SD) aortic cross-clamp time 78.5 (15.9) minutes Comparator (n = 20): mean (SD) age: 51.3 (14.7) years, 50% women, 70% rheumatic valvular disease, 100% permanent AF, mean duration of AF 25 months, mean ejection fraction 63%, 60% mitral valve repair, 40% mitral valve replacement, 25% “associated” surgery, mean (SD) cardiopulmonary bypass time 62 (23.8) minutes; mean (SD) aortic cross-clamp time 45.1 (21.1) minutes

Interventions

Intervention group 1 (SPVI): valve surgery + “simplified technique of surgical isolation of pulmonary veins” Intervention group 2 (maze): valve surgery + modified maze III procedure without cryoablation Comparator group: valve surgery + usual care

Outcomes

Not specified in methods or protocol; outcomes reported include: rhythm at 12 months, all-cause mortality, CVD mortality, CVD events, adverse events Mean (SD) follow-up: 35 (20) months Arrhythmia monitoring during follow-up: clinical evaluation and 12-lead ECG 1, 2, 3, 6 and 12 months

Notes

Participants in both intervention groups underwent left atrial appendage excision. Anti-arrhythmic drugs were not used routinely in the postoperative state but patients who were not in sinus rhythm underwent direct current cardioversion with amiodarone Funding: Financial support in part by Brazilian Ministry of Education: Agency CAPES/Program PROSUP and Research Foundation of Rio Grande do Sul

Author Manuscript

Risk of bias

Author Manuscript

Bias




Unclear risk



Unclear risk

“Immediately before the beginning of the operation, a sealed envelope was opened to indicate the procedure to be performed.” No mention if envelopes were opaque


High risk



High risk

Relied upon 12-lead ECG for outcome assessment; blinding of outcome assessors not reported


Low risk

No losses to follow-up


Unclear risk



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Author Manuscript

Other bias

High risk

Small-study bias

Blomstrom-Lundqvist 2007


Methods


Participants

65 participants aged 18–80 years with permanent AF and mitral valve disease requiring MV surgery; permanent AF defined as AF that had been present for > 3 months with failed or not attempted cardioversion in 4 university hospital centres in Sweden Exclusion criteria: NYHA IV heart failure, previous cardiac surgery other than CABG surgery, planned mitral valve surgery combined with other surgical procedures other than CABG surgery, tricuspid valvuloplasty, conditions that would impose an increased risk for prolonged surgical procedure, permanent pacemaker secondary to atrio-ventricular block, hyperthyroidism, geographical reasons, or unwillingness to participate Intervention (n = 34): mean (SD) age: 69.5 (7.9) years, 17% women, 97% mitral regurgitation, 3% mitral stenosis (mechanisms not reported), 100% permanent AF, mean ejection fraction 54%, 70% mitral valve repair, 30% mitral valve replacement, mean (SD) cardiopulmonary bypass time 146.6 (27.9) minutes; mean (SD) aortic cross-clamp time 87.4 (95.2) minutes Comparator (n = 35): mean (SD) age: 65.6 (8.8) years, 16% women, 100% mitral regurgitation (mechanisms not reported), 100% permanent AF, mean ejection fraction 57%, 80% mitral valve repair, 20% mitral valve replacement, mean (SD) cardiopulmonary bypass time 119.2 (33) minutes; mean (SD) aortic cross-clamp time 84.4 (23.3) minutes

Interventions

Intervention: valve surgery + left atrial cryoablation using argon-based cooling system (SurgiFrostTM Cryo Ablation System, CryoCath Technologies Inc., Quebec, Canada) Comparator group: valve surgery + usual care

Outcomes

Primary outcome: Sinus rhythm without documented episodes of AF at 6 months Secondary outcomes: Sinus rhythm after 12 months without recurrence of AF during preceding 6 months Health-related quality of life Morbidity Incidence of predefined adverse events Mean follow-up: 12 months Arrhythmia monitoring during follow-up: 12-lead ECG at 1, 6 and 12 months

Notes

Left atrial appendage excluded with suture. Usual care included: postoperative AF treated with sotalol or amiodarone infusion with up to 2 direct current cardioversions if AF recurred during hospital stay. Patients with AF at discharge scheduled for at least 1 direct current cardioversions 1 month after surgery. If patients had postoperative AF, then they were given prophylactic anti-arrhythmic drugs for 3 months Funding: Swedish Heart-Lung Foundation

Risk of bias

Author Manuscript

Bias




Low risk

Block randomisation described; almost certainly used valid randomisation method


Unclear risk

Not reported


Low risk

“Patients, personnel, and all physicians (excluding the operating team) were blinded to the allocated surgery, which was recorded separately from the patient’s surgical notes.”


High risk

High risk of bias for primary outcome because the authors relied upon 12-lead ECG for primary outcome assessment Low risk of bias for selected secondary outcomes (health-related quality of life, morbidity, adverse events)


High risk

Results analysed according to ITT principle but 6 participants randomised were excluded from the analyses for AF but were included in adverse events analyses


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Author Manuscript


High risk

Health-related quality of life outcomes not reported

Other bias

High risk

Small-study bias

Budera 2012


Methods


Participants

224 participants with coronary artery disease, valve disease, or both and paroxysmal, persistent, or long-standing persistent AF documented at least twice in the previous 6 months before surgery in Czech Republic Exclusion criteria: younger than 18 years; emergency surgery Intervention (n = 117): mean (SD) age: 69.9 (7.8) years, 43% women, 52% permanent AF, 26% persistent AF, 22% paroxysmal AF, mean ejection fraction 53%, 50% with mitral valve surgery, 50% without mitral valve surgery, mean (SD) cardiopulmonary bypass time 146.6 (27.9) minutes; mean (SD) aortic cross-clamp time 87.4 (95.2) minutes Comparator (n = 105): mean (SD) age: 65.6 (8.8) years, 16% women, 52% permanent AF, 26% persistent AF, 22% paroxysmal AF, mean ejection fraction 50%, 39% with mitral valve surgery, 61% without mitral valve surgery, mean (SD) cardiopulmonary bypass time 119.2 (33) minutes; mean (SD) aortic cross-clamp time 84.4 (23.3) minutes

Interventions

Intervention: surgery + LA modified maze (97% cryoablation and 3% radiofrequency ablation; epicardial ablation was performed if left atrium was not opened (e.g. CABG surgery, aortic or tricuspid surgery, or combination) and endocardial ablation was performed if left atrium was opened (e.g. mitral valve surgery) Comparator group: surgery + usual care, including postoperative amiodarone

Outcomes

Primary efficacy outcome: Sinus rhythm without any AF episodes during a 24-hr ECG at 1 year Primary safety outcome: Composite of death, MI, stroke, or new onset renal failure at 30 days Secondary outcomes: Composite of death, major bleeding, stroke, or hospitalisation for heart failure within 1 year of surgery Mean follow-up: not specifically reported Arrhythmia monitoring during follow-up: clinical evaluation and ECG at 1, 3, 6 and 12 months postoperative. Holter monitoring performed at 12-month follow-up. 5-year clinical, ECG, and Holter follow-up underway

Notes

Usual care included: anti-arrhythmic drugs were discontinued 3 months postoperatively if participants appeared to be free from AF Funding: Charles University Research projects

Risk of bias

Author Manuscript

Bias




Unclear risk

Method of randomisation not reported


Unclear risk

“…after informed consent was obtained, an envelope containing either ‘SA’ or ‘non-SA’ was opened” ”. No mention if envelopes were opaque


High risk

“The PRAGUE-12 trial was a prospective, open, Randomised multicentre clinical trial assessing the outcome of cardiac surgery with left atrial ablation vs. cardiac surgery alone (without ablation) in patients with coronary and/or valve disease and AF.”


High risk

“The PRAGUE-12 trial was a prospective, open, Randomised multicentre clinical trial assessing the outcome of cardiac surgery with left atrial ablation vs. cardiac surgery alone (without ablation) in patients with coronary and/or valve disease and AF.” “All of the follow-ups were performed in the participating cardiology centres.” “…nevertheless, the primary endpoint analysis was blinded since the Holter-ECGs were performed and analysed by arrhythmologists who did not have detailed information about the patients.”


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High risk

~10% loss to follow-up; 2 excluded post-randomisation, but 4 participants not accounted for in 30-day analyses (1 intervention, 3 control)


Low risk

Protocol available: NCT00665587

Other bias

Low risk

No other risk of biases identified

Cherniavsky 2014 Methods


Participants

95 participants from a single centre in Russia with coronary artery disease and persistent AF Inclusion criteria: i.

men or women who were aged 30–75 years (inclusive) on the day of signing the informed consent and were willing to comply with the study requirements;

Author Manuscript

ii.

presence of coronary artery disease with indications for CABG surgery;

iii.

presence of persistent AF (documented history of persistent AF, as defined by the ACC/AHA/ESC Guidelines;

iv.

ability to take the anticoagulant warfarin (Coumadin).

Exclusion criteria: i.

Wolff-Parkinson-White syndrome;

ii.

need for urgent cardiac surgery (e.g. cardiogenic shock);

iii.

contraindication for anticoagulation therapy;

iv.

pregnancy or desire to be pregnant within 12 months of the study treatment;

v.

current diagnosis of active systemic infection;

vi.

rheumatic heart disease;

Author Manuscript

vii.

history of CABG; and

viii.

presence of co-morbidities of other systems, which might lead to death within the first 3 years after surgery

Intervention group 1 (pulmonary vein isolation; n = 31); mean (SD) age: 64 (7) years, 23% women, 100% persistent AF; mean (SD) ejection fraction 55% (14); mean (SD) cardiopulmonary bypass time: 103 (37) minutes; mean (SD) aortic cross-clamp time: 71 (28) minutes Interventrion groups 2 (mini-Maze; n = 30); mean (SD) age: 62 (7) years, 17% women, 100% persistent AF; mean (SD) ejection fraction 56% (14); mean (SD) cardiopulmonary bypass time: 105 (37) minutes; mean (SD) aortic cross-clamp time: 73 (28) minutes Comparator group (n = 34); mean (SD) age: 64 (8) years, 26% women, 100% persistent AF; mean (SD) ejection fraction 53% (11); mean (SD) cardiopulmonary bypass time: 71 (41) minutes; mean (SD) aortic cross-clamp time: 48 (33) minutes

Author Manuscript

Interventions

Intervention group 1 (pulmonary vein isolation): CABG + Cardioblate bipolar RFA isolating pulmonary veins only + postoperative amiodarone for 3 months Intervention group 2 (mini-Maze): CABG + Cardioblate bipolar RFA isolating pulmonary veins plus RFA line to mitral annulus and left atrial appendage resection (MiniMaze) + postoperative amiodarone for 3 months Comparator: CABG alone

Outcomes

Primary outcome(s): Percentage of patients free of AF relapse lasting >30 seconds Secondary outcome(s): Health-related quality of life Mean (SD) follow-up: 14.4 (9.7) months Arrhythmia monitoring during follow-up: 3, 6, and 24 months using implantable loop recorder

Notes

Funding: Novosibirsk Research Institute of Circulation Pathology

Risk of bias Bias




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Unclear risk

Method for sequence generation not reported


Low risk

“The procedure of randomisation to CABG and PVI (CABG +PVI), CABG and MM (CABG+MM), and isolated CABG (CABG alone) groups was performed in blocks of 10 with an allocation ratio 1:1 using sequentially numbered, opaque, sealed envelopes. The designated person coordinating the study, who was not involved in filed procedures, was responsible for the preparation of the randomisation list.”


Low risk

“Patients participating in the study and the investigators evaluating the outcomes were blinded to group assignment” via implantable loop recorder


Low risk

“Patients participating in the study and the investigators evaluating the outcomes were blinded to group assignment” via implantable loop recorder “A Reveal XT feature, which stores the ECG of the detected episodes and the trend of more than 500 ventricular beats preceding the detection marker of the most recent AF episode, was used for final classification and validation through visual inspection.”


Low risk

“During follow-up in the CABG+PVI group, we failed to contact one patient. In the CABG+MM group, one patient was unable to attend the follow-up visit for family reasons.”


Unclear risk

No protocol available and authors did not respond to requests for information

Other bias

High risk

Small-study bias

Chevalier 2009


Methods


Participants

43 adult participants (> 18 years) with mitral valve disease and long-standing, persistent AF (> 6 months) in Lyon, France Exclusion criteria: ejection fraction < 35% and left atrial transverse diameter > 60 mm Intervention (n = 21): mean (SD) age: 69.1 (6.2) years, 76% women, 57% mitral regurgitation, 19% mitral stenosis, 100% persistent AF, mean ejection fraction 60%, 19% mitral valve repair, 46% mitral valve replacement, 14% aortic valve replacement, 5% tricuspid annuloplasty, mean (SD) aortic cross-clamp time 93 (32) minutes Comparator (n = 22): mean (SD) age: 66.3 (9.7) years, 50% women, 64% mitral regurgitation, 23% mitral stenosis, 100% persistent AF, mean ejection fraction 61%, 60% mitral valve repair, 81% mitral valve replacement, 14% aortic valve replacement, 27% tricuspid annuloplasty, mean (SD) aortic cross-clamp time 74 (19) minutes

Interventions

Intervention: surgery + LA modified maze with radiofrequency ablation (EP Technologies, Boston Scientific Corp, San Jose, CA) Comparator group: surgery + usual care

Outcomes

Primary outcome: Sinus rhythm at 12 months with no symptomatic or documented episodes of AF on repeated Holter monitoring during the entire follow-up period Secondary outcomes: Adverse surgical events, stroke, AF recurrence (any new episodes or episodes confirmed by ECG), death by any cause, undesirable events other than death Mean follow-up: 12 months Arrhythmia monitoring during follow-up: ECG and 24-hour Holter monitor with each visit (3 and 12 months)

Notes

“immediate postoperative treatment and prescription medication upon discharge were left up to the discretion of the physician in charge of the patient” The investigators planned to enrol 30 participants but enrolment was slower than anticipated and the trial was stopped due to lack of funding Funding: Ministere Francais de la Sante and promoted by hospices civils de Lyon

Risk of bias


Huffman et al.

Page 41


Bias




Low risk

Central randomisation, likely low risk of bias


Low risk

Central randomisation


High risk

Participants were blinded (low risk of bias) but personnel were not (high risk of bias)


Low risk

“upon discharge, the physician in charge of blinded follow-up examined the patient and collected data related to the endpoint criteria” Endpoints were also validated by an independent events committee, “made up of three cardiologists who did not otherwise participate in the study.”


Low risk

100% follow-up


Unclear risk


Other bias

High risk

Small-study bias; enrolment lower than planned

de Lima 2004 Randomised controlled, parallel group (1:1:1) trial

Participants

30 adult participants (18–75 years) referred for mitral valve surgery with clinical and haemodynamic criteria for elective mitral valve surgery with permanent AF (> 6 months before surgery) in Brazil Exclusion criteria: previous cardiac surgery, pregnant, LV ejection fraction < 20% Intervention group 1 (pulmonary vein isolation; n = 10): mean (SD) age: 54.1 (9.4) years, 70% women, 80% rheumatic valve disease, 100% permanent AF, mean ejection fraction 64%, proportion of surgery type not reported by subgroup, mean (SD) cardiopulmonary bypass time 98 (3) minutes Intervention group 2 (maze; n = 10): mean (SD) age: 50.1 (15.3) years, 70% women, 70% rheumatic valve disease, 100% permanent AF, mean ejection fraction 64%, proportion of surgery type not reported by subgroup, mean (SD) cardiopulmonary bypass time 115 (25) minutes Comparator (n = 10): mean (SD) age: 50.1 (15.4) years, 40% women, 70% rheumatic valve disease, 100% permanent AF, mean ejection fraction 64%, proportion of surgery type not reported by subgroup, mean (SD) cardiopulmonary bypass time 68 (22) minutes

Interventions

Intervention group 1 (pulmonary vein isolation): mitral valve surgery + en bloc pulmonary vein isolation Intervention group 2 (maze): mitral valve surgery + modified maze III (“ablation of the terminal points of the incisions was performed by electrocoagulation instead of the cryoablation used in the original technique”) Comparator: mitral valve surgery (including left atrial appendage ligation in patients in whom left atrial appendage thrombi were present) + usual care

Outcomes

Primary outcome: Sinus rhythm maintenance Secondary outcome(s): Not reported Mean follow-up: not specifically reported Arrhythmia monitoring during follow-up: clinic visits at 2, 6, 12, 18, and 24 months; 24-hour Holter monitor at 6 months

Notes

Usual care included amiodarone for at least 30 days and recurrent AF was “aggressively treated by pharmacologic or electrical cardioversion” Funding: not reported

Author Manuscript

Methods

Author Manuscript

Risk of bias


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Bias




Low risk

“In the period between June 1999 and February 2001 30 patients with permanent AF and mitral valve disease were randomly divided into three groups of 10 patients each, using a system of 30 sealed envelopes to ensure a blind selection.” Not entirely clear but likely low risk of bias for this domain


Unclear risk

As above; no mention of whether or not the envelopes were opaque or not


High risk



Low risk

“Twenty-four-hour ECG monitoring examinations (Holter ECG) were performed using a DMI-Cardiology (Burdick, Deerfield, WI) analysis center, and analyzed by the same operator blinded for the patient group.”


Unclear risk

Follow-up unclear


High risk

“patients who exhibited recurrent AF were excluded from the followup analyses of the sinus rhythm maintenance”

Other bias

High risk

Small-study bias

Deneke 2002


Methods


Participants

30 adult participants with chronic AF (permanent AF for >1 year or at least 2 unsuccessful medical or electrical cardioversions 6 months before surgery) undergoing mitral valve replacement in Germany Exclusion criteria: not reported Intervention (n = 15): mean (range) age: 64.7 (49–75) years, 60% women, mitral valve disease type not reported by group, 100% permanent AF, mean ejection fraction 64%, 100% mitral valve replacement, mean cardiopulmonary bypass time 188 minutes, mean aortic cross-clamp time 103 minutes Comparator (n = 15): mean (range) age: 69.7 (64–77) years, 60% women, mitral valve disease type not reported by group, 100% permanent AF, mean ejection fraction 61%, 100% mitral valve replacement, mean cardiopulmonary bypass time 127 minutes, mean aortic cross-clamp time 85 minutes

Interventions

Intervention: mitral valve replacement + bi-atrial radiofrequency maze Comparator: mitral valve replacement + usual care

Outcomes

Primary outcome(s): Sinus rhythm at postoperative follow-up Secondary outcome(s): “clinical” outcome, survival, atrial transport function, functional capacity Mean (SD) follow-up: intervention 22 (7) months, control 21 (6) months Arrhythmia monitoring during follow-up: clinic visits at 3, 6, 9, and 12 months; ECG monitoring at each visit and 24-hour Holter monitor at 6 and 12 months

Notes

Usual care included sotalol 80 mg bid for 6 months, then patients were switched to metoprolol Funding: not reported

Risk of bias Bias




Unclear risk

“After informed consent was obtained in all patients, they were consecutively Randomised to undergo either mitral valve surgery and antiarrhythmic surgery (modified MAZE operation) (group A) or mitral valve surgery without antiarrhythmic surgical intervention (group B).” Methods of randomisation not reported.


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Unclear risk

Not reported


High risk



Unclear risk

Not reported


Low risk

“12-month follow-up was completed in all but 2 surviving patients from group B, who were unable to attend the hospital but had documented (on an outpatient clinic ECG) AF (one patient unable to travel to our hospital, one patient with severe psychosis).”


Unclear risk


Other bias

High risk

Small-study bias

Doukas 2005

Author Manuscript

Methods


Participants

97 adult participants (1 excluded post-randomisation) referred for mitral valve surgery with permanent AF in single hospital (Glenfield Hospital) in Leicester, England Exclusion criteria: sick sinus syndrome, uncontrolled hyperthyroidism, permanent pace-maker, or previous cardiac surgery Intervention (n = 49): mean (SD) age: 67.2 (9) years, 37% women, 22% rheumatic valve disease, 73% degenerative mitral valve disease, 4% ischaemic mitral valve disease, 100% permanent AF, mean ejection fraction 57%, 77% mitral valve repair, 23% mitral valve replacement, mean (SD) cardiopulmonary bypass time 106 (34) minutes, mean (SD) aortic cross-clamp time 70 (26) minutes Comparator (n = 48): mean (SD) age: 67 (8) years, 50% women, 23% rheumatic valve disease, 67% degenerative mitral valve disease, 10% ischaemic mitral valve disease, 100% permanent AF, mean ejection fraction 58%, 71% mitral valve repair, 29% mitral valve replacement, mean (SD) cardiopulmonary bypass time 99 (37) minutes, mean (SD) aortic cross-clamp time 64 (28) minutes

Interventions

Intervention: mitral valve surgery + monopolar left atrial radiofrequency maze (EP Technologies, Boston Scientific Corp, San Jose, CA) Comparator: mitral valve surgery (including left atrial ligation) + usual care

Outcomes

Primary outcome: Presence of sinus rhythm at 12 months Secondary outcomes: Functional status, exercise capacity, left atrial contractility, and left atrial and left ventricular dimensions and function, plasma levels of BNP Mean follow-up: 12 months Arrhythmia monitoring during follow-up: clinic visits at 3, 6, and 12 months; ECG and 24-hour Holter monitoring at each visit and in the presence of symptoms suggestive of dysrhythmia

Notes

Usual care included amiodarone for 3 months. If patients were in sinus rhythm, the anti-arrhythmic drugs were stopped at 3 months. If patients remained in AF, then they were treated with antiarrhythmic drugs Funding: British Heart Foundation

Author Manuscript

Risk of bias Bias




Low risk

“Randomised blocks of between 4 and 6 were prepared for each subgroup in advance by a computer-generated numbers…”


Low risk

“assignment took place on the day of the operation by picking the next envelope for the relevant group by a person masked to the previous allocations”


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High risk

Participants were blinded (low risk of bias) but personnel were not (high risk of bias)


Low risk

“assessors of outcomes were blinded to group assignment”


Low risk

100% follow-up; deaths not included in the primary outcome assessment in the report but included in this analysis


Low risk

Outcomes match protocol: NCT00238706

Other bias

Low risk


Gillinov 2015 Methods


Participants

260 adult participants with persistent or long-standing persistent AF who required mitral valve surgery in 20 centres in United States and Canada Exclusion criteria: 1

AF without indication for mitral valve surgery

2

AF is paroxysmal

3

Evidence of active infection

4

Mental impairment or other conditions that may not allow subject to understand the nature, significance, and scope of study

Author Manuscript

5

Surgical management of hypertrophic obstructive cardiomyopathy

6

Previous catheter ablation for AF

7

Life expectancy of less than one year

8

Absolute contraindications for anticoagulation therapy

9

Enrolment in concomitant drug or device trials

10

Uncontrolled hypo- or hyperthyroidism

11

FEV1 < 30% of predicted value

12

Women who are pregnant as evidenced by positive pregnancy test

13

Women of childbearing age who do not agree to be on adequate birth control throughout the period of the trial

Author Manuscript

Intervention group 1 (pulmonary vein isolation; n = 67): mean (SD) age: 71.3 (10) years, 43% women, 57% degenerative mitral valve disease, 36% functional mitral valve disease, 8% ischaemic mitral valve disease, 49% persistent AF, 51% long-standing persistent AF, mean ejection fraction 56%, 62% mitral valve repair, 37% mitral valve replacement, mean (SD) cardiopulmonary bypass time 143 (66) minutes, mean (SD) aortic cross-clamp time 98 (39) minutes Intervention group 2 (modified bi-atrial maze; n = 66): mean (SD) age: 68.2 (10) years, 42% women, 56% degenerative mitral valve disease, 29% functional mitral valve disease, 15% ischaemic mitral valve disease, 46% persistent AF, 55% long-standing persistent AF, mean ejection fraction 55%, 56% mitral valve repair, 44% mitral valve replacement, mean (SD) cardiopulmonary bypass time 152 (61) minutes, mean (SD) aortic cross-clamp time 107 (44) minutes Comparator (n = 127): mean (SD) age: 69.4 (10) years, 50% women, 58% degenerative mitral valve disease, 38% functional mitral valve disease, 5% ischaemic mitral valve disease, 44% persistent AF, 56% long-standing persistent AF, mean ejection fraction 56%, 52% mitral valve repair, 48% mitral valve replacement, mean (SD) cardiopulmonary bypass time 133 (51) minutes, mean (SD) aortic cross-clamp time 96 (36) minutes Interventions

Intervention group 1 (pulmonary vein isolation): mitral valve surgery + pulmonary vein isolation (unipolar, bipolar, or cryoablation) Intervention group 2 (modified bi-atrial maze): mitral valve surgery + modified bi-atrial maze (unipolar, bipolar, or cryoablation)


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Comparator: mitral valve surgery (including left atrial ligation) + usual care Outcomes

Primary outcomes: 1

Freedom from AF at both 6 months and 12 months

2

Primary safety endpoint-composite of death, stroke, heart failure, MI, rehospitalisation for cardiac causes, transient ischaemic attack, PE, bleeding, sternal wound, permanent pacemaker, oesophageal damage, within 3 days after procedure or hospital discharge

Secondary outcome: 1

Composite of major cardiac and cerebrovascular adverse events (death, stroke, hospitalisation for heart failure, worsening heart failure), mortality, need for rhythm-related interventions, health-related quality of life

2

Mean follow-up: not specifically reported Arrhythmia monitoring during follow-up: telephonic follow-up at 3, 6, and 9 months, clinic visits at 12 months; 72-hour Holter monitoring at 6 and 12 months

Author Manuscript

Notes

Funding: National Institutes of Health, Canadian Institutes of Health Research

Risk of bias


Bias




Low risk

“Eligible patients were randomly assigned, in a 1:1 ratio, to undergo either surgical ablation or no ablation (control group) during the mitral-valve operation after the induction of anesthesia. Patients in the ablation group underwent further randomization to one of two lesion sets: pulmonary-vein isolation or biatrial maze. Randomization was performed after intra-operative trans-esophageal echocardiography confirmed the absence of a left atrial thrombus. Randomization was stratified according to center.”


Unclear risk

Site of randomisation not reported


High risk

“Neither patients nor investigators will be blinded to treatment” [protocol]


Low risk

“Those assessing the primary outcome will be blinded to patients’ treatment assignment.”


High risk

Data were imputed for outcomes in 25/ 127 participants in the mitral valve surgery group and in 27/133 participants in the mitral valve surgery + ablation group (CONSORT flow diagram in Supplemental Appendix)


Low risk

Outcomes match protocol: NCT00238706 and Supplemental Appendix

Other bias

Low risk


Jessurun 2003 Methods

Randomised controlled, parallel group (2.5:1) trial

Participants

35 adult participants (< 75 years) selected for mitral valve surgery with symptomatic AF, irrespective of type and duration in The Netherlands Exclusion criteria: < 18 years or >75 years Concomitant aortic valve surgery, congenital repair, or CABG with > 3 distal anastomoses Previous mitral valve surgery EF < 25% PAP > 75% systemic pressures


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Author Manuscript

PVR > 5 Wood units Severe lung disease Impaired renal function (creatinine > 150 micromol/L Limited life expectancy (< 2 years) Intervention (n = 25): mean (SD) age: 64 (12) years, 44% women, 72% rheumatic valve disease, 28% degenerative mitral valve disease, 52% paroxsymal AF, 48% permanent AF, mean ejection fraction 45%, 40% mitral valve repair, 60% mitral valve replacement, mean (SD) cardiopulmonary bypass time 155 (27) minutes, mean (SD) aortic cross-clamp time 90 (24) minutes Comparator (n = 10): mean (SD) age: 64 (9) years, 50% women, 40% rheumatic valve disease, 60% degenerative mitral valve disease, 20% paroxysmal AF, 80% permanent AF, mean ejection fraction 45%, 60% mitral valve repair, 40% mitral valve replacement, mean (SD) cardiopulmonary bypass time 97 (27) minutes, mean (SD) aortic cross-clamp time 60 (18) minutes

Author Manuscript

Interventions

Intervention: mitral valve surgery + maze III Comparator: mitral valve surgery + usual care

Outcomes

Primary outcome: Sinus rhythm without AF following mitral valve surgery Secondary outcomes: Death, stroke, preserved sinus node function, and quality of life (SF-36) Mean follow-up: 12 months Arrhythmia monitoring during follow-up: clinic visit, 12-lead ECG and one-channel 48 hour Holter monitoring at 3 and 12 months after surgery

Notes

Usual care included: oral anticoagulation; “…antiarrhythmic drugs were discontinued except if AF or other atrial arrhythmias resumed. In those cases, sotalol, digitalis, or quinidine were temporarily prescribed for rate control and/or prevention of these arrhythmias. Before discharge, electrical cardioversion was done if AF persisted despite an appropriate drug regimen. In patients without maze surgery the antiarrhythmic drug regimen was optimized in order to facilitate the onset of sinus rhythm; thereafter, electrical cardioversion was considered if chronic AF was present in less than approximately 3 years.” Funding: “The Quality of Life Study was granted by the foundation ‘Friends of the St. Antonius Hospital’, Nieuweigein, The Netherlands”

Risk of bias


Bias




Unclear risk

Methods of randomisation not reported, and the authors include a statement conflating sequence generation/concealment with blinding: “…randomization could not be done in a single, or double blind manner.”


Unclear risk

Methods of randomisation not reported, and the authors include a statement conflating sequence generation/concealment with blinding: “…randomization could not be done in a single, or double blind manner.”


High risk

As above, not blinded and likely high risk of bias for this domain


High risk

As above, not blinded and likely high risk of bias for this domain


Low risk

100% follow-up


Unclear risk


Other bias

High risk

Small-study bias

Jonsson 2012 Methods


Participants

72 adult participants (> 18 years) primarily scheduled for mitral valve surgery with long-lasting AF of more than 12 months duration prior to surgery in Sweden and Finland. Due to slow enrolment,


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the inclusion criteria was modified to: “long-lasting atrial fibrillation for at least 6 months prior to surgery or AF ongoing for at least 3 months prior to surgery and a history of previously failed cardioversion or relapse after initially successful cardioversion” Exclusion criteria: prior valve surgery, concomitant aortic valve surgery, prior catheter ablation for AF, documented torsade de pointes, permanent pacemaker treatment, hyperthyroidism ruled out by blood-test, active endocarditis, severe calcifications of the mitral anulus, unforeseen events developing during the surgical procedure whereby adding ablation imposes an unproportional risk to the procedure or inability, unwillingness to follow the protocol Intervention (n = 35): mean (SD) age: 66 (7.7) years, 16% women, 94% mitral regurgitation, 100% “long-lasting” AF, mean (SD) AF duration 87 (110) months, 10% ejection fraction < 50%, 91% mitral valve repair, 10% mitral valve replacement, mean (SD) cardiopulmonary bypass time 146 (36) minutes, mean (SD) aortic cross-clamp time 109 (30) minutes Comparator (n = 35): mean (SD) age: 67 (9.2) years, 45% women, 91% mitral regurgitation, 100% “long-lasting” AF, mean (SD) AF duration 65 (62) months, 12% ejection fraction < 50%, 76% mitral valve repair, 24% mitral valve replacement, mean (SD) cardiopulmonary bypass time 133 (36) minutes, mean (SD) aortic cross-clamp time 95 (28) minutes

Author Manuscript

Interventions

Intervention: mitral valve surgery + bi-atrial microwave ablation (Afx Inc., Fremont, CA) Comparator: mitral valve surgery + usual care

Outcomes

Primary outcome: Preserved sinus rhythm at 12 month follow-up determined by 12-lead ECG “preserved” ECG = sinus rhythm on 12-lead ECG without any documented episodes (or cardioversions) of AF, flutter, or tachycardia since previous follow-up Secondary outcomes: Freedom from AF, flutter, or tachycardia at the 12-month follow-up determined by 24-hour Holter ECG, at 6 months after surgery determined by 12-lead ECG, pacemaker requirement, antiarrhythmic treatment, health-related quality of life, and incidence of adverse effects according to protocol Mean follow-up: not specifically reported Arrhythmia monitoring during follow-up: clinic visit, 12-lead ECG at 1, 3, 6, and 12 months after surgery, and 24-hour Holter monitoring 12 months after surgery

Notes

Usual care included: bisoprolol for rate control while inpatient and direct current cardioversion upon discharge if patients remained in AF. If patients had AF recurrence from discharge to 4 months, then they were treated with sotalol or amiodarone (if contraindications to sotalol). All class III drugs were discontinued at 6 months after surgery if sinus rhythm ensued Funding: not reported

Risk of bias


Bias




Low risk

“computer-based randomization was performed by an external resource”


Low risk

“each hospital received sealed envelopes in numbered series with a balance between patients assigned for ablation vs controls. At the day of the surgery the cardiac surgeon opened the envelopes in order, designating the allocated study treatment”


High risk

“all patients and with the exception of the surgical team, all personnel involved in the follow-up, was blinded to the assigned treatment” Low risk of bias (participants) and high risk of bias (personnel)


Low risk

“all patients and with the exception of the surgical team, all personnel involved in the follow-up, was blinded to the assigned treatment”


High risk

1 participant lost to follow-up and 5 participants died. Not reported why these participants were excluded from baseline and operative analyses


High risk

Health-related quality of life outcomes not reported


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Author Manuscript

Other bias

Unclear risk

Definition of “long-lasting AF” changed in the middle of trial due to poor enrolment. Uncertain how this might bias the results but important to note the protocol change

Khargi 2001

Author Manuscript

Methods


Participants

30 adult participants (> 18 years) with documented chronic AF, pre-existing for more than 1 year, and mitral valve disease in Germany Exclusion criteria: not reported Intervention (n = 15): mean (SD) age: 64.7 (NR) years, 40% women, 100% “chronic” AF, 13% mitral valve repair, 87% mitral valve replacement, mean (range) cardiopulmonary bypass time 188 (165–230) minutes, mean (range) aortic cross-clamp time 103 (86–134) minutes Comparator (n = 15): mean (SD) age: 69.7 (NR) years, 20% women, 100% “chronic” AF, 100% mitral valve replacement, mean (range) cardiopulmonary bypass time 127 (60–97) minutes, mean (range) aortic cross-clamp time 84 (38–112) minutes

Interventions

Intervention: mitral valve surgery + bi-atrial saline-irrigated, cooled-tip radiofrequency ablation (SICTRA, Sprinklr; Medtronic, Minneapolis, MN) Comparator: mitral valve surgery (including left atrial appendage closure) + usual care

Outcomes

Primary outcome: Not reported Secondary outcomes: Not reported Mean follow-up: not specifically reported Arrhythmia monitoring during follow-up: clinic visit, 12-lead ECG, and 24-hour Holter monitor at 6 and 12 months after surgery

Notes

Usual care included: For the first 20 patients, direct current cardioversion if AF persisted for 24 hours, which was abandoned for the last 10 patients. Sotalol 40 mg twice daily on first postoperative day, 80 mg twice daily on postoperative day 3 and eventually to 160 mg twice daily if no bradyarrhythmias were present. Sotalol was stopped at 6 months and replaced by metoprolol Funding: not reported

Risk of bias


Bias




Unclear risk



Unclear risk



High risk



Unclear risk

Not reported


High risk

“the 12 month follow-up was complete, although 2 group B [control] patients were unable to revisit our outpatient cardiology clinics”


Unclear risk


Other bias

High risk

Protocol changes throughout manuscript; small-study bias

Knaut 2010 Methods



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Participants

45 adult participants (> 18 years) with an existing indication to coronary bypass and/or aortic valve surgery with additional permanent AF (≥ 1 month) and LVEF ≥ 30% in Dresden, Germany Exclusion criteria: emergency operations, age 18 years) with first diagnosed paroxysmal AF and indication for CABG surgery in Russia. AF defined by “documented” AF episodes ≥ 1 hOUr in duration with ≥ 2 episodes over 4 months with ECG documentation of one episode Exclusion criteria: i.

Previous treatment with IC or class III antiarrhythmic drugs

ii.

Previous heart surgery and AF ablation procedure


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iii.

Requiring concomitant valve surgery

iv.

Left ventricle ejection fraction < 35%

v.

Left atrial diameter > 55 mm

vi.

Unwillingness to participate

Intervention (n = 18): mean (SD) age: 59 (6) years, 22% women, 100% paroxysmal AF, mean ejection fraction 59%, 100% CABG surgery, mean (SD) cardiopulmonary bypass time 111 (9) minutes, mean (SD) aortic cross-clamp time 59 (11) minutes Comparator (n = 17): mean (SD) age: 60 (8) years, 29% women, 100% paroxysmal AF, mean ejection fraction 58%, 100% CABG surgery, mean (SD) cardiopulmonary bypass time 108 (8) minutes, mean (SD) aortic cross-clamp time 56 (9) minutes

Author Manuscript

Interventions

Intervention: CABG surgery + pulmonary vein isolation with bipolar radiofrequency ablation (Cardioblate, Medtronic, Minneapolis, MN) without left atrial appendage ligation Comparator: CABG surgery + usual care

Outcomes

Primary outcome: AF-free survival at 18 months (AF-free < 0.5%) Secondary outcomes: Percentage of AF burden defined through continuous monitoring using an implantable loop recorder Thromboembolic events Procedural complications Mean follow-up: 18 months Arrhythmia monitoring during follow-up: follow-up at 1, 3, 6, 9, 12, and 18 months with implantable loop recorder and AF defined as > 0.5% of time in AF (not absolute time based)

Notes

Usual care was notable for: “all patients were free from AAD therapy before and after surgery at least until the end of the follow-up, but all of them were taking beta-blockers” Funding: not reported but one author was an employee for Medtronic, Inc

Risk of bias


Bias




Unclear risk

“The study was a prospective, Randomised and single blind and was designed to compare the two treatment methods: (i) CABG only (n = 17) and (ii) CABG with concomitant PVI (n = 18).” Methods of randomisation not reported


Unclear risk



High risk



Low risk

Implantable loop recording outcome assessment “blinded”


Low risk

100% follow-up


Unclear risk


Other bias

High risk

Study author is industry employee; small-study bias

Schuetz 2003 Methods


Participants

43 adult participants with permanent AF, who had been unsuccessfully treated previously, presented for surgical treatment of valve disease, CABG surgery, or both in Munich, Germany Exclusion criteria: none reported


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Intervention (n = 24): mean (SD) age: 64.6 (10) years, 50% women, 100% permanent AF, mean (SD) duration of AF 3.8 (2.8) years, mean ejection fraction 63%, 67% mitral valve surgery, 13% CABG surgery, 20% other surgery, mean (SD) cardiopulmonary bypass time 121 (27) minutes, mean (SD) aortic cross-clamp time 100 (25) minutes Comparator (n = 19): mean (SD) age: 70.2 (8) years, 26% women, 100% permanent AF, mean (SD) duration of AF 9.2 (9.2) years, mean ejection fraction 54%, 37% mitral valve surgery, 26% CABG surgery, 37% other surgery, mean (SD) cardiopulmonary bypass time 103 (45) minutes, mean (SD) aortic cross-clamp time 74 (44) minutes

Author Manuscript

Interventions

Intervention: surgery + microwave ablation (AFx Inc., Fremont, CA) with left atrial size reduction, including left atrial appendage exclusion Comparator: surgery + usual care

Outcomes

Primary outcome: Not reported Secondary outcomes: Not reported Mean follow-up: not specifically reported Arrhythmia monitoring during follow-up: clinic and ECG follow-up at 3, 6, and 12 months after surgery and 24-hour Holter monitoring 12 months after surgery

Notes

Usual care included: anticoagulation for 3 months and “amiodarone or sotalol as antiarrhythmic medication if sinus rhythm was successfully restored and no contraindications were given” Funding: not reported

Risk of bias

Author Manuscript

Bias




Unclear risk

Methods of randomisation not reported (asked by audience member in the discussion section but no answer provided)


Unclear risk



High risk



Unclear risk

Not reported


High risk

9 lost to follow-up in intervention group and 10 lost to follow-up in control group; all individuals lost to follow-up were not in sinus rhythm at 3 months


Unclear risk


Other bias

High risk

Small-study bias

Srivastava 2008

Author Manuscript

Methods

Randomised controlled, parallel group (1:1:1:1) trial

Participants

160 participants with chronic rheumatic AF undergoing valvular heart surgery in Mumbai, India. Chronic AF was defined as AF of more than three months duration (with ECG documentation) Exclusion criteria: 1

Patients receiving antiarrhythmic drugs preoperatively.

2

Age less than 12 years and more than 60 years.

3

Pregnancy.

4

LA size more than 6 cm.

5

Previous midline sternotomy.


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6

Patients with active coronary artery disease requiring additional CABG surgery

Intervention group 1 (pulmonary vein isolation, n = 40): mean (SD) age: 41.0 (11. 4) years, 50% women, 100% permanent AF, mean AF duration 12.6 months, 100% rheumatic valve disease, 83% mitral valve replacement, 8% mitral valve repair, 8% mitral valvulotomy Intervention group 2 (left atrial modified maze, n = 40): mean (SD) age: 36.0 (8.0) years, 45% women, 100% permanent AF, mean AF duration 12.5 months, 100% rheumatic valve disease, 100% mitral valve replacement Intervention group 3 (bi-atrial modified maze, n = 40): mean (SD) age: 37.1 (11.1) years, 55% women, 100% permanent AF, mean AF duration 9.8 months, 100% rheumatic valve disease, 87% mitral valve replacement, 3% mitral valve repair, 10% mitral valvulotomy Comparator (n = 40): mean (SD) age: 36.7 (9.8) years, 43% women, 100% permanent AF, mean AF duration 12.2 months, 100% rheumatic valve disease, 90% mitral valve replacement, 3% mitral valve repair, 7% mitral valvulotomy

Author Manuscript

Interventions

Intervention group 1 (pulmonary vein isolation): surgery + pulmonary vein isolation using radiofrequency micro-bipolar coagulation (RFMC) Intervention group 2 (left atrial modified maze): surgery + left atrial modified maze using radiofrequency micro-bipolar coagulation (RFMC) and cryoablation applied to AV junction and coronary sinus Intervention group 3 (bi-atrial modified maze): surgery + bi-atrial modified maze using radiofrequency micro-bipolar coagulation (RFMC) and cryoablation applied to AV junction and coronary sinus Comparator: surgery + usual care

Outcomes

Primary outcomes: •

Conversion to normal sinus rhythm.

•

AF free survival at one-year duration.

Secondary outcome(s): None reported Arrhythmia monitoring during follow-up: clinic and ECG evaluation every 3 months Mean follow-up: 3 years, 8 months Notes

Usual care included: direct current cardioversion on postoperative day 7 if in AF. During followup, participants in AF were put on oral amiodarone for two months and underwent repeat cardioversion if still in AF Funding: none

Author Manuscript

Risk of bias

Author Manuscript

Bias




Low risk

“The four groups were labelled as 1, 2, 3 and 4 and a computergenerated table of random numbers (including the four groups) was obtained. Depending on the order in which the patients were operated on, they were allocated to one of the groups as per the random numbers table”


Unclear risk



High risk

“Single blind” study; personnel not blinded


High risk

“Single blind” study; outcome assessors not blinded


High risk

High loss to follow-up throughout and only ECG used for evaluation of recurrent AF


Unclear risk



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Other bias

Low risk


van Breugel 2010


Methods


Participants

150 participants with paroxysmal or persistent AF documented for at least 3 months prior to surgery as defined by the ACC/AHA/ESC guidelines who are undergoing valvular and/or coronary surgery in Maastricht or Breda, The Netherlands Exclusion criteria: sick sinus syndrome or contraindication to oral anticoagulants Intervention (n = 75): mean (SD) age: 61.9 (11.4) years, 42% women, 42% paroxysmal AF, 23% long-standing persistent AF, 34% permanent AF, mean ejection fraction 49%, 63% “valve replacement”, 28% isolated CABG surgery, 15% combined valve + CABG surgery Comparator (n = 75): mean (SD) age: 71.0 (9.8) years, 29% women, 45% paroxysmal AF, 22% long-standing persistent AF, 31% permanent AF, mean ejection fraction 57%, 63% “valve replacement”, 34% CABG surgery, 30% combined valve + CABG surgery

Interventions

Intervention: valve surgery +/− coronary bypass graft surgery + microwave energy ablation (Microwave generator by Guidant) for pulmonary vein isolation (includes resection of left atrial appendage) Comparator: valve surgery +/− coronary bypass graft surgery (includes resection of left atrial appendage) + usual care

Outcomes

Primary outcome(s): 2010 report: “Health-related quality of life and maintenance of sinus rhythm at 1-year follow-up after surgery, as stated on the outpatient visit and measured on an EKG and 24-hour Holter registration, were considered as primary endpoints of the total study.” 2011 report: “Maintenance of sinus rhythm at one-year follow-up after surgery and HrQoL were considered as primary end points, morbidity, mortality and cost-effectiveness as secondary outcomes.” Trial registration (NCT01019759): “Percentage of patients free from AF, as apparent from 24-hour Holter registration, in addition to standard ECG. For the purpose of this primary endpoint, AF was defined as lasting longer than 10 seconds.” Secondary outcome(s): Trial registration (NCT01019759): Quality of life (QoL) [Time Frame: at 3, 6 and 12 months postoperative ] Cost-effectiveness [Time Frame: intraoperative until 12 months postoperative] In-hospital morbidity (including pulmonary complications, resternotomy for surgical bleeding, cerebrovascular accidents, acute MI, renal failure, development of atrioventricular conduction abnormalities) [Time Frame: postoperative, in-hospital period ] Rhythm-related events and interventions (including electrical or chemical cardioversion, percutaneous catheter ablation, implantation of a defibrillator, pacemaker implantation) [ Time Frame: discharge until 12 months postoperative ] Out-of-hospital morbidity (including acute MI, percutaneous catheter ablation, implantation of a defibrillator, pacemaker implantation and cerebrovascular accidents, syncope) [ Time Frame: discharge until 12 months postoperative ] Mortality [ Time Frame: intraoperative until 12 months postoperative] Mean (SD) follow-up: 351 (147) days Arrhythmia monitoring during follow-up: clinic evaluation and ECG at 3, 6, and 12 months and Holter monitoring at 12 months

Notes

Usual care included: “prophylactic sotalol for at least 4 weeks postoperatively, additional digoxin for rate control, oral anticoagulants for at least 3 months depending on rhythm outcome, and cardioversion after 3 days of persistent AF” Funding: none

Risk of bias

Author Manuscript

Bias




Unclear risk

“Patients were randomly assigned to ‘surgery as usual’ or ‘add-on arrhythmia surgery’ by a computerized randomization program on the day before surgery. To assure an equal distribution of patients undergoing valvular and/or coronary surgery in both treatment arms, patients were stratified after inclusion but before randomization.” However, major difference in age (10 years) between intervention and control groups


Unclear risk

Method of allocation concealment not reported

Blinding of participants and personnel

High risk

“Patients and all medical personnel (with exception of the surgical team) were blinded to their group assignment.”


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Author Manuscript

(performance bias) All outcomes Blinding of outcome assessment (detection bias) All outcomes

Unclear risk

“Patients and all medical personnel (with exception of the surgical team) were blinded to their group assignment.” Not reported if the surgical team performed outcome assessments


High risk

Data from only 132/150 participants reported because these were the individuals who completed at least one health-related quality of life assessment


High risk

Major differences between trial registrations and between one trial registration and reported outcomes. Both trial registrations were also posted after trial completion

Other bias

Low risk


Author Manuscript

Vasconcelos 2004 Methods


Participants

29 adult (< 60 years) participants with persistent AF documented for at least 6 months prior to surgery with left atrial diameter < 65 mm who are undergoing mitral valve surgery for chronic rheumatic heart disease at a single centre in Sao Paulo, Brazil Exclusion criteria:

Author Manuscript

a.

Antecedents of acute MI

b.

Atherosclerotic coronary lesions determining thinning of the lumen of any vessel greater than 50%

c.

Important tricuspid insufficiency - established according to clinical, echocardiographic, and haemodynamic criteria

d.

Tricuspid stenosis

e.

Important pulmonary hypertension - established according to haemodynamic or echocardiographic criteria, defined as systolic pressure of the pulmonary artery equal to or greater than 60 mmHg

f.

Significant functional impairment of the left ventricle - left ventricular ejection fraction determined on echocardiography equal to or lower than 30% and/or left ventricular diameter equal to or greater than 70 mm

g.

Idiopathic dilated cardiomyopathy

h.

Hypertrophic cardiomyopathy

i.

Chagasic cardiomyopathy

j.

Collagenoses

k.

Chronic obstructive pulmonary disease

l.

Chronic renal insufficiency requiring dialytic treatment

m.

Primary thyroid disease

n.

Contraindications to the use of amiodarone

Author Manuscript

Intervention (n = 15): mean (SD) age: 49.4 (10.1) years, 73% women, 100% long-standing persistent AF, mean (SD) duration of AF 23.8 (20) months, 100% rheumatic valve disease, mean ejection fraction 68%, 93% mitral valve replacement, 7% mitral valve commisurotomy, mean (SD) cardiopulmonary bypass time 106 (17) minutes Comparator (n = 14): mean (SD) age: 50.8 (9.7) years, 57% women, 100% long-standing persistent AF, mean (SD) duration of AF 33.9 (28.5) months, 100% rheumatic valve disease, mean ejection fraction 66%, 100% mitral valve replacement, mean (SD) cardiopulmonary bypass time 78.2 (24.4) minutes Interventions

Intervention: valve surgery + left atrial modified cut-and-sew maze (includes resection of left atrial appendage) Comparator: valve surgery + usual care

Outcomes

Primary outcome: Freedom from AF Secondary outcome(s): None reported


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Author Manuscript

Mean (SD) follow-up: 10.3 month for intervention group, 11.5 months for control group Arrhythmia monitoring during follow-up: via “a portable device” Notes

Usual care included: postoperative amiodarone during the first 3 weeks after surgery and oral anticoagulation Funding: none reported

Risk of bias


Bias




Unclear risk

Methods of randomisation not described


Unclear risk



High risk



Unclear risk

“After discharge from the hospital, the patients were followed up monthly by the same observer with clinical and electrocardiographic assessment.” Not reported if the observer was blinded or not


High risk

2/29 participants lost to follow-up and excluded from analyses


Unclear risk


Other bias

High risk

Small-study bias

von Oppell 2009

Author Manuscript

Methods


Participants

49 adult (< 60 years) participants with persistent or permanent AF who are undergoing cardiac surgery at a single centre in Cardiff, Wales Exclusion criteria: none reported Intervention (n = 24): mean (SD) age: 66 (8) years, 67% women, 8% long-standing persistent AF, 92% permanent AF, mean (SD) duration of AF 23.8 (20) months, 58% rheumatic valve disease, mean ejection fraction 52%, 33% mitral valve replacement, 67% mitral valve replacement, 29% concomitant aortic valve surgery, 42% concomitant CABG surgery, mean (SD) cardiopulmonary bypass time 176 (42) minutes, mean (SD) aortic cross-clamp time 143 (35) minutes Comparator (n = 25): mean (SD) age: 68 (9) years, 44% women, 12% long-standing persistent AF, 88% permanent AF, 40% rheumatic valve disease, mean ejection fraction 55%, 40% mitral valve replacement, 60% mitral valve replacement, 24% concomitant aortic valve surgery, 64% concomitant CABG surgery, mean (SD) cardiopulmonary bypass time 160 (55) minutes, mean (SD) aortic cross-clamp time 119 (44) minutes

Interventions

Intervention: surgery + bi-atrial modified maze with radiofrequency ablation using Cardioblate system (Medtronic, Minneapolis, MN); initial 6 participants underwent bipolar ablation but the subsequent 18 participants underwent monopolar ablation Comparator: surgery + usual care (20/25 had left atrial appendix excision)

Outcomes

Primary outcome: None reported Secondary outcome(s): None reported Mean (SD) follow-up: 10.3 month for intervention group, 11.5 months for control group Arrhythmia monitoring during follow-up: 12-lead ECG at 3 months and 1 year; 24-hour Holter monitoring at 3 months

Notes

Usual care included: anti-arrhythmic drugs and oral anticoagulation for the first 3 months after surgery; up to 2 direct current cardioversion attempts in the first 6 months


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Author Manuscript

Funding: Medtronic Bakken Research Center Risk of bias

Author Manuscript

Bias




Low risk

“In terms of the randomisation, this was computer-generated randomisation sealed in blinded envelopes prior to the commencement of the study, and the blinded envelopes were only opened at the time of surgery.”


Low risk

“In terms of the randomisation, this was computer-generated randomisation sealed in blinded envelopes prior to the commencement of the study, and the blinded envelopes were only opened at the time of surgery.”


High risk

“single-blind” “patients were blinded with regard to which group they were randomised to prevent bias during completion of quality of life questionnaires.” Personnel were not blinded


High risk

Personnel were not blinded during outcome assessment, which included only 1 Holter monitor per participants at 3 months after surgery


Low risk

100% follow-up


Unclear risk


Other bias

High risk

Small-study bias; senior author was Medtronic employee

Wang 2014


Methods


Participants

210 adult (> 18 years) participants with AF > 6 months at rheumatic mitral valve disease who are undergoing cardiac surgery at a single centre in Beijing, China (initial recruitment target 150 participants according to protocol) Exclusion criteria: AF duration ≤ 6 months, age < 18 years old, emergency operation, left atrial dimension > 70 mm, left ventricular ejection fraction < 30%, left atrial thrombus, onset of acute myocardial infarction < 6 weeks, time of apoplexy < 6 months Intervention group 1 (left atrial radiofrequency maze, n = 70): mean (SD) age: 52.3 (10. 3) years, 60% women, 100% long-standing persistent AF, mean (SD) duration of AF 34.5 (20.6) months, 100% rheumatic valve disease, mean ejection fraction 61%, 100% mitral valve replacement, mean (SD) cardiopulmonary bypass time 101 (34) minutes, mean (SD) aortic cross-clamp time 72.1 (28) minutes Intervention group 2 (bi-atrial radiofrequency maze, n = 70): mean (SD) age: 53.1 (10) years, 67% women, 100% long-standing persistent AF, mean (SD) duration of AF 31. 4 (27.2) months, 100% rheumatic valve disease, mean ejection fraction 61%, 100% mitral valve replacement, mean (SD) cardiopulmonary bypass time 138.2 (46) minutes, mean (SD) aortic cross-clamp time 143 (39) minutes Comparator (n = 70): mean (SD) age: 53.6 (10) years, 59% women, 100% long-standing persistent AF, mean (SD) duration of AF 33.7 (20.9) months, 100% rheumatic valve disease, mean ejection fraction 61%, 100% mitral valve replacement, mean (SD) cardiopulmonary bypass time 85.3 (35) minutes, mean (SD) aortic cross-clamp time 61.9 (25) minutes

Interventions

Intervention group 1: mitral valve replacement + left atrial modified maze with monopolar radiofrequency ablation using Cardioblate system (Medtronic, Minneapolis, MN), including left atrial appendage excision Intervention group 2: mitral valve replacement + bi-atrial modified maze with monopolar radiofrequency ablation using Cardioblate system (Medtronic, Minneapolis, MN), including biatrial appendage excision Comparator: mitral valve replacement (including left atrial appendage excision) + amiodarone for 1 year

Outcomes

Primary outcome(s): 1 year outcomes: cardiac death, stroke, and recurrent AF after discharge; secondary endpoints include recurrent atrial tachycardia (a combination of AF, atrial flutter, and other types of atrial tachycardia [lasting more than 30 seconds]), prosthetic dysfunction, and pacemaker implantation


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Author Manuscript

Reported in clinicaltrials.gov: “At 3rd, 6th and 12th month’s follow-up, to evaluate the rhythm status by ECG and 24-hour Holter and cardiac hemodynamic status by transthoracic echocardiography” 3-month blanking period. Secondary outcome(s): None reported Mean (SD) follow-up: 12 months Arrhythmia monitoring during follow-up: ECG and Holter monitoring at 3, 6, and 12 months Notes

Usual care included: oral anticoagulation; amiodarone × 3 months in the intervention groups Funding: China National Center for Cardiovascular Diseases

Risk of bias


Bias




Low risk

“The random table was generated by the SAS software”


Unclear risk



Unclear risk

“After randomisation, the study processes were blinded to the patients, coordinators and the investigators who were responsible for the patient assessment but were not blinded to participant surgeons” Low risk of bias for participants; high risk of bias for personnel caring for the participants


Low risk

“After randomisation, the study processes were blinded to the patients, coordinators and the investigators who were responsible for the patient assessment but were not blinded to participant surgeons” “Blinded adjudication board includes two senior cardiologists involved in assessment and classification of endpoints”


Low risk

100% follow-up reported


Low risk

Similar outcomes reported in the report compared with the study protocol (NCT01013688)

Other bias

Low risk


AF = atrial fibrillation, AV = aortic valve, BNP = brain natriuretic peptide, CI = confidence interval, CVD = cardiovascular disease, CABG = coronary artery bypass graft, ECG = electrocardiogram, FEV1 = forced expiratory volume in 1 second, ITT = intention-to-treat, IV = intravenous, LA = left atrium, LAA = left atrial appendage, LVEF = left ventricular ejection fraction, MI = myocardial infarction, MV = mitral valve, NR = not reported, PE = pulmonary embolism, PVI = pulmonary vein isolation, RFA = radiofrequency ablation, SD = standard deviation, SPVI: surgical isolation of the pulmonary veins

Characteristics of excluded studies [ordered by study ID]

Author Manuscript

Study

Reason for exclusion

Ailawadi 2011

Wrong intervention

Al Halabi 2015

Wrong patient population

Al-Atassi 2014


Al-Khatib 2014

Wrong study design

Assasi 2012

Wrong study design

Basu 2012

Wrong study design

Biancari 2010


Bockeria 2011

Wrong study design


Huffman et al.

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Study


Breda 2008


Budera 2015

Wrong study design

Camm 2011

Wrong study design

CEDIT 2006

Wrong study design

Cheng 2010

Wrong study design

CNHTA 2010

Wrong study design

Damiano 2003

Wrong study design

DECIT-CGATS 2009

Wrong study design

Deneke 2001

Wrong comparator

Deneke 2002a

Wrong comparator

Doulkas 2004

Incorrect citation

Dunning 2013

Wrong study design

ECRI 2004

Wrong study design

Emmert 2014

Wrong intervention

Hazel 2004

Wrong study design

Healey 2005

Wrong intervention

Hornero 2001

Wrong study design

Hornero 2003

Wrong study design

Je 2015


Kearney 2014

Wrong comparator

Khargi 2005

Wrong study design

Kong 2009

Wrong study design

Kong 2010

Wrong study design

Krul 2013

Wrong study design

Lebedev 2008

Wrong intervention

Lemke 2000

Full-text unavailable

Lins 2010

Wrong study design

Liu 2010

Wrong comparator

MacDonald 2012

Wrong study design

Molina 2008

Wrong study design

Nagpal 2009

Wrong intervention

NCT00157807

Participants were not recruited before study terminated

NICE 2005

Wrong study design

NICE 2005a

Wrong study design

NICE 2005b

Wrong study design

NICE 2006

Wrong study design

NICE 2010

Wrong study design

Ninet 2005

Wrong study design

Ontario 2006

Wrong study design


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Study


Padanilam 2015

Wrong study design

Passage 2010

Wrong study design

Phan 2014

Wrong study design

Phan 2014a

Wrong study design

Phan 2015

Wrong study design

Pires 2010

Wrong comparator

Quenneville 2009

Wrong study design

Reents 2014

Wrong intervention

Reston 2005

Wrong study design

Senatore 2001

Wrong comparator

Tsai 2015

Wrong intervention

Vicol 2005

Terminated with no participants recruited

Whitlock 2013

Wrong intervention

Wong 2006a

Wrong study design

Zhang 2012

Wrong study design

Characteristics of studies awaiting assessment [ordered by study ID] ChiCTR-TRC-07003039

Author Manuscript

Methods

Randomised, parallel group trial

Participants

Patients with rheumatic heart valve disease with AF

Interventions

Intervention: Valve replacement plus Cox IV Comparator: Valve replacement only

Outcomes Notes

Trial name: A prospective single-center clinical trial of radiofrequency ablation maze procedure in surgical treatment of rheumatic heart valve disease (ChiCTR-TRC-07003039) Starting date: 5 May 2006 Contact information: Wang Huisan Department of Cardiovascular Surgery General Hospital of Shenyang Military Command [email protected] Retrospective registration Status: unknown Reason: no response to email requests for information

NCT00735722

Author Manuscript

Methods

Randomised, parallel group, single-blind intervention study

Participants

Patients with AF and first time on-pump coronary artery bypass grafting or aortic valve replacement

Interventions

Intervention: CABG plus HIFU AF ablation (Epicor) Comparator: CABG alone

Outcomes Notes

Trial name: A(f )MAZE-CABG Study (AFMAZE-CABG; NCT00735722) Starting date: July 2009 Contact information: Malcolm Dalrymple-Hay Plymouth Hospitals NHS Trust Department of Cardiac Surgery Derriford Hospital, Plymouth, Devon PL6 8DH


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Author Manuscript

United Kingdom Email: [email protected] (Susan Ridolfo, medical secretary) Sponsored by St. Jude Medical Status: Terminated Reason reported: “insufficient recruitment” Last updated: October 2011 No response to email requests for information NCT01791218 Methods

Single-centre, prospective, single blind, randomised interventional study

Participants

Patients with paroxysmal AF undergoing elective coronary artery bypass grafting and aortic valve replacement for aortic stenosis

Interventions

Intervention: CABG, AVR, or CABG+AVR plus pulmonary vein isolation Comparator: CABG, AVR, or CABG+AVR alone

Outcomes Notes

Author Manuscript

Trial name: Surgical Pulmonary Vein Isolation Efficiency Study (FIN-PVI, NCT01791218) Starting date: November 2012 Contact information: Teemu Riekkinen Kuopio University Hospital 358044175527 [email protected] Status: Terminated Reason reported: low recruitment according to Dr. Reikinnen but no additional information provided

AF = atrial fibrillation, AVR = aortic valve replacement, CABG = coronary artery bypass graft, HIFU = high intensity focused ultrasound,

Characteristics of ongoing studies [ordered by study ID] ISRCTN14454361

Author Manuscript

Trial name or title

A randomised controlled trial to investigate the biochemical and myocardial effects of ablation for AF at concomitant elective cardiac surgery with two different methods, freezing versus heating (RAFT-MSR; ISRCTN14454361)

Methods

Single-centre, prospective randomised interventional study

Participants

Patients with rheumatic heart valve disease with AF

Interventions

Intervention 1: Mitral valve surgery with or without other cardiac procedures and concomitant cryo-maze ablation device. Ablation lines according to Cox-Maze IV procedure Intervention 2: Mitral valve surgery with or without other cardiac procedures and concomitant radio frequency (RF)-maze ablation device. Ablation lines according to Cox-Maze IV procedure Comparator: Mitral valve surgery with or without other cardiac procedures

Outcomes

Author Manuscript

Starting date

September 2013

Contact information

Dr. Farkas Vánky Dept. of Cardiothoracic and Vascular Surgery University Hospital Linköping (Sweden) [email protected]

Notes

Retrospective registration Status: ongoing Expected study completion date: December 2016 No response to email requests for information

ISRCTN82731440 Trial name or title

The Amaze trial: a randomised controlled trial to investigate the clinical and cost-effectiveness of adding an ablation device-based maze procedure as a routine adjunct to elective cardiac surgery for patients with pre- existing AF (ISRCTN82731440; UKCRN ID 5245)

Methods

Multicentre, prospective, double-blind, randomised controlled trial


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Author Manuscript

Participants

Elective cardiac surgical patients undergoing major cardiac surgery (such as coronary, valve or combined operations) with a history of paroxysmal, persistent or chronic AF beginning more than 3 months before the date of the operation

Interventions

Intervention: surgery plus any AF ablation device that is routinely used within the NHS by the investigators Comparator: surgery alone

Outcomes Starting date

September 2008

Contact information

Mr Samer Nashef Papworth Hospital NHS Foundation Trust [email protected]

Notes

Expected study completion date: July 2017 No response to email requests for information

NCT01360918

Author Manuscript

Trial name or title

Concomitant epicardial pulmonary vein isolation in patients with AF undergoing elective cardiac surgery (CONTROL-AF, NCT01360918)

Methods

Randomised, open-label trial

Participants

Patients with AF admitted for elective cardiac surgery

Interventions

Intervention: surgery + epicardial pulmonary vein isolation using Medtronic Cardioblate BP2 Comparator: surgery


September 2005

Contact information

Bob Oude Velthius, MD, MSc Medisch Spectrum Twente [email protected]

Notes

Sponsored by Medisch Spectrum Twente Status: ongoing, recruitment (N=8) completed and follow-up extended at the request of the ethics board Expected study completion date: November 2015

Author Manuscript

NCT01649544 Trial name or title

Comparison of treatment of atrial fibrillation (AF) between surgical ultrasonic technology or drug therapy for patients with AF requiring mitral valve surgery (EPICAF, NCT01649544)

Methods

Randomised parallel control

Participants

Patients with mitral valve disease requiring surgery with AF (LA < 55 mm)

Interventions

Intervention: Valve surgery plus ablation using EPICOR device Comparator: Valve surgery only plus amiodarone for 2 months

Outcomes

Author Manuscript

Starting date

23 July 2012

Contact information

Antoine Da Costa, MD, PhD Centre Hospitalier Universitaire de Saint Etienne [email protected]

Notes

Expected study completion date: September 2015 but no response to email requests for information in March 2016

UMIN000016129 Trial name or title

Surgical Ablation for Non Mitral Operation: Randomised multi-Institutional Trial and optimiZation (SAN- MORITZ study; JPRN-UMIN000016129)

Methods

Randomised, parallel group, single-blind intervention study

Participants

Patients with AF and first time on-pump coronary artery bypass grafting or aortic valve replacement

Interventions

Intervention: Surgery plus pulmonary vein isolation for paroxysmal AF Comparator: Surgery with left atrial appendage resection


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Author Manuscript


6 January 2015

Contact information

Takashi Kunihara The Cardiovascular Institute Division of Cardiovascular Surgery Tokyo [email protected]

Notes

Funded by Century Medical, Inc. Status: Enrolling Last updated: January 2015 No response to email requests for information

AF = atrial fibrillation. LA = left atrium

DATA AND ANALYSES Author Manuscript

Comparison 1

Atrial fibrillation surgery versus no atrial fibrillation surgery Outcome or subgroup title


No. of studies

No. of participants

1 All-cause mortality

20

1829

Statistical method Risk Ratio (M-H, Fixed, 95% CI)

1.14 [0.81, 1.59]

2 Freedom from atrial fibrillation, atrial flutter, and atrial tachycardia off antiarrhythmic medications > 3 months after surgery

8

649

Risk Ratio (M-H, Fixed, 95% CI)

2.04 [1.63, 2.55]

3 Freedom from atrial fibrillation, atrial flutter, or atrial tachycardia

22

1899


2.46 [2.16, 2.80]

4 Adverse events as defined by investigators

9

858


1.07 [0.85, 1.34]

5 Permanent pacemaker implantation

18

1726


1.69 [1.12, 2.54]

6 30-day mortality

18

1566


1.25 [0.71, 2.20]

7 Mediastinitis

3

290


1.49 [0.24, 9.12]

8 Cardiac tamponade

3

166


0.34 [0.07, 1.67]

9 Neurologic or thromboembolic events

14

1155


1.05 [0.60, 1.83]

10 Need for surgical reexploration

9

929


1.05 [0.58, 1.91]

11 Cardiovascular mortality

9

496


1.82 [0.72, 4.60]

12 Fatal and nonfatal cardiovascular events

8

826


1.17 [0.86, 1.59]

13 Freedom from atrial fibrillation

15

1500

Risk Ratio (M-H, Random, 95% CI)

2.55 [2.01, 3.24]

14 30-day rehospitalisation

1

260


1.36 [1.06, 1.75]

15 Need for post-discharge direct current cardioversion

6

352


1.11 [0.49, 2.49]

16 Freedom from atrial fibrillation, flutter, or

2

70


2.54 [1.47, 4.36]


Effect size

Huffman et al.

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Author Manuscript

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

17 Freedom from atrial fibrillation, flutter, or tachycardia >3 months (cutand-sew only)

4

124


2.49 [1.60, 3.87]

18 Freedom from atrial fibrillation, flutter, or tachycardia >3 months (nonmitral valve surgery only)

3

175


1.89 [1.41, 2.53]

tachycardia >3 months (paroxsymal atrial fibrillation only)


Analysis 1.1.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 1 Allcause mortality.


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Analysis 1.2.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 2 Freedom from atrial fibrillation, atrial flutter, and atrial tachycardia off anti-arrhythmic medications > 3 months after surgery.

Author Manuscript Author Manuscript Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22.

Huffman et al.

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Analysis 1.3.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 3 Freedom from atrial fibrillation, atrial flutter, or atrial tachycardia.

Author Manuscript Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22.

Huffman et al.

Page 66


Analysis 1.4.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 4 Adverse events as defined by investigators.


Huffman et al.

Page 67


Analysis 1.5.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 5 Permanent pacemaker implantation.


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Author Manuscript Author Manuscript Analysis 1.6.

Author Manuscript

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 6 30day mortality.

Author Manuscript

Analysis 1.7.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 7 Mediastinitis.


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Analysis 1.8.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 8 Cardiac tamponade.


Analysis 1.9.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 9 Neurologic or thromboembolic events.


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Page 70


Analysis 1.10.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 10 Need for surgical re-exploration.


Analysis 1.11.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 11 Cardiovascular mortality.


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Page 71


Analysis 1.12.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 12 Fatal and nonfatal cardiovascular events.


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Author Manuscript Author Manuscript Analysis 1.13.

Author Manuscript

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 13 Freedom from atrial fibrillation.

Author Manuscript

Analysis 1.14.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 14 30day rehospitalisation.


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Analysis 1.15.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 15 Need for post-discharge direct current cardioversion.

Author Manuscript

Analysis 1.16.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 16 Freedom from atrial fibrillation, flutter, or tachycardia >3 months (paroxsymal atrial fibrillation only).


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Analysis 1.17.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 17 Freedom from atrial fibrillation, flutter, or tachycardia >3 months (cut-and-sew only).

Author Manuscript

Analysis 1.18.

Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 18 Freedom from atrial fibrillation, flutter, or tachycardia >3 months (non-mitral valve surgery only).


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Page 75


Figure 1.

PRISMA flow chart of included studies.


Huffman et al.

Page 76


Figure 2.

‘Risk of bias’ graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.


Huffman et al.

Page 77


Figure 3.

‘Risk of bias’ summary: review authors’ judgements about each risk of bias item for each included study.


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Page 78


Figure 4.

Funnel plot of comparison: 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, outcome: 1.2 Freedom from atrial fibrillation, atrial flutter, and atrial tachycardia off antiarrhythmic medications > 3 months after surgery.


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Figure 5.

Funnel plot of comparison: 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, outcome: 1.3 Freedom from atrial fibrillation, atrial flutter, or atrial tachycardia.


Author Manuscript Turkey Brazil Sweden Czech Re- public

Russia France Brazil Germany UK

USA, Canada Netherlands Sweden, Finland Germany

Germany Russia Germany India

Albrecht 2009

Blomstrom- Lundqvist 2007

Budera 2012

Cherniavsky 2014

Chevalier 2009

de Lima 2004

Deneke 2002

Doukas 2005

Gillinov 2015

Jessurun 2003

Jonsson 2012

Khargi 2001

Knaut 2010

Pokushalov 2012

Schuetz 2003

Srivastava 2008

Brazil

Abreu Filho 2005

Akpinar 2003

Country

Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 August 22. 160

43

35

45

30

72

35

260

97

30

30

43

95

224

65

60

67

70

N

MV

CABG, MV, TV, AV

CABG

CABG, AV

MV

MV

MV

MV

MV

MV

MV

MV

CABG

MV, CABG, AV

MV

MV

MV

MV

Primary cardiac surgery

Author Manuscript

Study

Cryo or RF

Microwave

RF

Microwave

(Cut and sew) RF intraatrial lesions

Microwave

Cut-and- sew

Cryo ± RF

RF

RF

Cut-and- sew

RF

RF

97% Cryo 3% RF

Cryo

Cut-and- sew

RF

RF

Technique

Intervention

X

X

X

X

X

X

X

X

X

*

X

RA

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

LA

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

PVI

60

12

18

12

12

12

12

12

12

12

24

12

24

12

12

60

18

12

Longest follow-up (months)

Author Manuscript

Summary of included studies

ECG every 3 months

ECG and 24-hr Holter at 3, 6, 12 months

ILR data collection at 1, 3, 6, 9, 12, 18 months

ECG and 24-hr Holter at 6, 12 months

ECG and 24-hr Holter at 6, 12 months

ECG at 1, 3, 6, 12 months; ETT at 6 months; 24-hr Holter at 12 months

ECG at 3, 12 months; 24-hr Holter at 3, 12 months

72-hr Holter at 6, 12 months

ECG at 3, 6, 12 months; 24-hr Holter at 6, 12 months if patient mentioned symptoms suggestive of arrhythmia

ECG at 3, 6, 9, and 12 months; 24-hr Holter at 6, 12 months

ECG at 2, 6, 12, 18, and 24 months; ETT and 24-hr Holter at 6 months

ECG and 24-hr Holter at discharge, 3, and 12 months

ILR data collection at 3, 6, 24 months

ECG at 1, 3, 6, 12 months; 24-hr Holter at 12 months (5-year follow- up planned)

ECG at 1, 2, 3, 6, 12 months

ECG and ETT every 6 months

ECG at 6, 12, > 12 months

ECG at each clinic visit; 24-hr Holter at 3, 6, 12 months

Outpatient arrhythmia monitoring

Author Manuscript

Table 1 Huffman et al. Page 80

Brazil UK China

Vasconcelos 2004

von Oppell 2009

Wang 2014

210

49

29

150

MV

MV

MV

MV ± CABG

RF

RF

Cut-and- sew

Microwave

Technique

Intervention

X

X

RA

X

X

X

LA

X

X

X

X

PVI

12

12

24

12

Longest follow-up (months)

ECG and 24-hr Holter at 3, 6, 12 months

ECG at 3, 12 months; 24-hr Holter at 3 months

ECG, “portable device” - time frame not reported

ECG at 3, 6, 12 months; 24-hr Holter at 12 months

Outpatient arrhythmia monitoring

RA = right atrium, LA = left atrium, PVI = pulmonary vein isolation, MV = mitral valve, RF = radiofrequency ablation, ECG = electrocardiogram, ETT = exercise treadmill test, Cryo = cryoablation, CABG = coronary artery bypass grafting, AV = aortic valve, ILR = implantable loop recorder, TV = tricuspid valve

RA ablation performed only if RA opened for TV inspection or ASD repair

*

Netherlands

Author Manuscript

van Breugel 2010

Primary cardiac surgery

Author Manuscript N

Author Manuscript

Country

Author Manuscript

Study

Huffman et al. Page 81


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Concomitant ablation of atrial fibrillation during mitral surgery.

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