Abstract
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.
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.
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 random‐effects 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.
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 moderate‐quality 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, high‐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? 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. 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. 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.
Summary of findings
Summary of findings for the main comparison. Concomitant atrial fibrillation surgery for people undergoing cardiac surgery.
| 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) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | |
| Risk with no atrial fibrillation surgery | Risk with concomitant atrial fibrillation surgery | ||||
| All‐cause mortality | Study population | RR 1.14 (0.81 to 1.59) | 1829 (20 RCTs) | ⊕⊕⊝⊝ LOW 1,2 | |
| 66 per 1000 | 75 per 1000 (53 to 105) | ||||
| Freedom from AF/AFL/AT off antiarrhythmic medications > 3 months | Study population | RR 2.04 (1.63 to 2.55) | 649 (8 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | |
| 241 per 1000 | 492 per 1000 (393 to 615) | ||||
| Investigator‐defined adverse events | Study population | RR 1.07 (0.85 to 1.34) | 858 (9 RCTs) | ⊕⊝⊝⊝ VERY LOW 1,2,3 | |
| 236 per 1000 | 252 per 1000 (201 to 316) | ||||
| Pacemaker implantation4 | Study population | RR 1.69 (1.12 to 2.54) | 1726 (18 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | |
| 41 per 1000 | 69 per 1000 (46 to 104) | ||||
| 30‐day mortality4 | Study population | RR 1.25 (0.71 to 2.20) | 1566 (18 RCTs) | ⊕⊕⊝⊝ LOW 1,2 | |
| 23 per 1000 | 29 per 1000 (16 to 51) | ||||
| *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 | |||||
1Downgraded due to study limitations, largely driven by high risk of detection bias and small‐study bias.
2Downgraded due to imprecision.
3Downgraded due to publication (reporting) bias.
4 Individual adverse event related to procedural safety.
Background
Description of the condition
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).
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.
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).
Description of the intervention
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
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). 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).
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).
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).
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.
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.
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
Secondary outcomes
Cardiovascular mortality
Fatal and non‐fatal cardiovascular events, including myocardial infarction, stroke, transient ischaemic attack, or heart failure
Freedom from atrial fibrillation
30‐day rehospitalisation
Need for post‐discharge direct current cardioversion
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)
Cochrane Database of Systematic Reviews: Issue 3 of 12, March 2016
Cochrane Central Register of Controlled Trials (CENTRAL): Issue 2 of 12, February 2016
Database of Abstracts of Reviews of Effect (DARE): Issue 2 of 4, April 2015
Health Technology Assessment Database (HTA): Issue 1 of 4, January 2016
Ovid MEDLINE(R) 1946 to March Week 4 2016
Ovid MEDLINE(R) In‐Process & Other Non‐Indexed Citations March 30, 2016
Embase 1974‐present; Embase Classic 1947‐1973; MEDLINE 1966‐present (embase.com)
Conference Proceedings Citation Index‐Science (CPCI‐S) 1990‐present (Web of Science)
ClinicalTrials.gov (searched 1 April 2016)
World Health Organization International Clinical Trials Registry Platform (WHO ICTRP; http://apps.who.int/trialsearch/; searched 1 April 2016)
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
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).
1.
PRISMA flow chart of included studies.
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.
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.
Random sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias) and of outcome assessors (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other potential sources of bias
We judged 'Risk of bias' criteria as “low risk”, “high risk”, or “unclear risk” and evaluated individual bias items as described in theCochrane 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”.
2.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
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).
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.
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.
Assessment of heterogeneity
In the event of substantial clinical, methodological, or statistical heterogeneity (I² greater than 50%), we either performed a random‐effects meta‐analysis 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 meta‐analysis (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).
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 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 Table 1 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.
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)
Type of AF surgery (cut‐and‐sew versus radiofrequency ablation)
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.
Restricting the analysis to published studies
Restricting the analysis by taking into account risk of bias, as specified in the Assessment of risk of bias in included studies section
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.
Results
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 full‐text 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 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).
Included studies
Table 2 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.
1. Summary of included studies.
| Study | Country | N | Primary cardiac surgery | Intervention | Longest follow‐up (months) | Outpatient arrhythmia monitoring | |||
| Technique | RA | LA | PVI | ||||||
| Abreu Filho 2005 | Brazil | 70 | MV | RF | X | X | X | 12 | ECG at each clinic visit; 24‐hr Holter at 3, 6, 12 months |
| Akpinar 2003 | Turkey | 67 | MV | RF | * | X | 18 | ECG at 6, 12, > 12 months | |
| Albrecht 2009 | Brazil | 60 | MV | Cut‐and‐sew | X | X | X | 60 | ECG and ETT every 6 months |
| Blomstrom‐Lundqvist 2007 | Sweden | 65 | MV | Cryo | X | X | 12 | ECG at 1, 2, 3, 6, 12 months | |
| Budera 2012 | Czech Republic | 224 | MV, CABG, AV | 97% Cryo 3% RF |
X | X | 12 | ECG at 1, 3, 6, 12 months; 24‐hr Holter at 12 months (5‐year follow‐up planned) |
|
| Cherniavsky 2014 | Russia | 95 | CABG | RF | X | X | X | 24 | ILR data collection at 3, 6, 24 months |
| Chevalier 2009 | France | 43 | MV | RF | X | X | 12 | ECG and 24‐hr Holter at discharge, 3, and 12 months | |
| de Lima 2004 | Brazil | 30 | MV | Cut‐and‐sew | X | X | X | 24 | ECG at 2, 6, 12, 18, and 24 months; ETT and 24‐hr Holter at 6 months |
| Deneke 2002 | Germany | 30 | MV | RF | X | X | X | 12 | ECG at 3, 6, 9, and 12 months; 24‐hr Holter at 6, 12 months |
| Doukas 2005 | UK | 97 | MV | RF | X | X | 12 | ECG at 3, 6, 12 months; 24‐hr Holter at 6, 12 months if patient mentioned symptoms suggestive of arrhythmia | |
| Gillinov 2015 | USA, Canada | 260 | MV | Cryo ± RF | X | X | X | 12 | 72‐hr Holter at 6, 12 months |
| Jessurun 2003 | Netherlands | 35 | MV | Cut‐and‐sew | X | X | X | 12 | ECG at 3, 12 months; 24‐hr Holter at 3, 12 months |
| Jonsson 2012 | Sweden, Finland | 72 | MV | Microwave | X | X | X | 12 | ECG at 1, 3, 6, 12 months; ETT at 6 months; 24‐hr Holter at 12 months |
| Khargi 2001 | Germany | 30 | MV | (Cut and sew) RF intraatrial lesions | X | X | X | 12 | ECG and 24‐hr Holter at 6, 12 months |
| Knaut 2010 | Germany | 45 | CABG, AV | Microwave | X | 12 | ECG and 24‐hr Holter at 6, 12 months | ||
| Pokushalov 2012 | Russia | 35 | CABG | RF | X | 18 | ILR data collection at 1, 3, 6, 9, 12, 18 months | ||
| Schuetz 2003 | Germany | 43 | CABG, MV, TV, AV | Microwave | X | X | 12 | ECG and 24‐hr Holter at 3, 6, 12 months | |
| Srivastava 2008 | India | 160 | MV | Cryo or RF | X | X | X | 60 | ECG every 3 months |
| van Breugel 2010 | Netherlands | 150 | MV ± CABG | Microwave | X | X | 12 | ECG at 3, 6, 12 months; 24‐hr Holter at 12 months | |
| Vasconcelos 2004 | Brazil | 29 | MV | Cut‐and‐sew | X | 24 | ECG, “portable device” ‐ time frame not reported | ||
| von Oppell 2009 | UK | 49 | MV | RF | X | X | X | 12 | ECG at 3, 12 months; 24‐hr Holter at 3 months |
| Wang 2014 | China | 210 | MV | RF | X | X | X | 12 | ECG and 24‐hr Holter at 3, 6, 12 months |
*RA ablation performed only if RA opened for TV inspection or ASD repair
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
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
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 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.
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.
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.
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.
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 anti‐arrhythmic medications > 3 months after surgery.
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.
Effects of interventions
See: Table 1
Key results are reported in the Table 1, 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.
1.1. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 1 All‐cause mortality.
1.2. Analysis.
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.
1.3. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 3 Freedom from atrial fibrillation, atrial flutter, or atrial tachycardia.
1.4. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 4 Adverse events as defined by investigators.
1.5. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 5 Permanent pacemaker implantation.
1.6. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 6 30‐day mortality.
1.7. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 7 Mediastinitis.
1.8. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 8 Cardiac tamponade.
1.9. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 9 Neurologic or thromboembolic events.
1.10. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 10 Need for surgical re‐exploration.
1.11. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 11 Cardiovascular mortality.
1.12. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 12 Fatal and nonfatal cardiovascular events.
1.14. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 14 30‐day rehospitalisation.
1.15. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 15 Need for post‐discharge direct current cardioversion.
1.16. Analysis.
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).
1.17. Analysis.
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).
1.18. Analysis.
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).
Primary outcomes
All‐cause mortality
There was low‐quality evidence demonstrating no difference in all‐cause 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.
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.
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).
Secondary outcomes
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).
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).
1.13. Analysis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 13 Freedom from atrial fibrillation.
Thirty‐day rehospitalisation
There was low‐quality evidence of increased risk for 30‐day rehospitalisation (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 health‐related 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 €74,724 (95% uncertainty interval (UI), €72,770, €76,678) and was not considered cost‐effective with an incremental cost‐effectiveness ratio of €73,359 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.
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 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.
Quality of the evidence
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
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 (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.
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.
What's new
| Date | Event | Description |
|---|---|---|
| 2 March 2020 | Amended | Conflict of interest declaration amended (Declarations of interest) for clarification of compliance with the Cochrane conflict of interest policy, which includes the relevant parts of the Cochrane Commercial Sponsorship Policy. |
Acknowledgements
Parts of the Methods section are based on a standard template established by the Cochrane Metabolic and Endocrine Disorders Group.
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
#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) In‐Process & 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.
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"
Embase 1974‐present; Embase Classic 1947‐1973; MEDLINE 1966‐present (embase.com)
#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
#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
Conference Proceedings Citation Index‐ Science (CPCI‐S) ‐‐1990‐present (Web of Science)
#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
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
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
Recruitment status: ALL
April 1, 2015—87 records for 85 trials found
Data and analyses
Comparison 1. Atrial fibrillation surgery versus no atrial fibrillation surgery.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 All‐cause mortality | 20 | 1829 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.14 [0.81, 1.59] |
| 2 Freedom from atrial fibrillation, atrial flutter, and atrial tachycardia off anti‐arrhythmic 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 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.46 [2.16, 2.80] |
| 4 Adverse events as defined by investigators | 9 | 858 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [0.85, 1.34] |
| 5 Permanent pacemaker implantation | 18 | 1726 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.69 [1.12, 2.54] |
| 6 30‐day mortality | 18 | 1566 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.25 [0.71, 2.20] |
| 7 Mediastinitis | 3 | 290 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.49 [0.24, 9.12] |
| 8 Cardiac tamponade | 3 | 166 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.34 [0.07, 1.67] |
| 9 Neurologic or thromboembolic events | 14 | 1155 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.60, 1.83] |
| 10 Need for surgical re‐exploration | 9 | 929 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.58, 1.91] |
| 11 Cardiovascular mortality | 9 | 496 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.82 [0.72, 4.60] |
| 12 Fatal and nonfatal cardiovascular events | 8 | 826 | Risk Ratio (M‐H, Fixed, 95% CI) | 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 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [1.06, 1.75] |
| 15 Need for post‐discharge direct current cardioversion | 6 | 352 | Risk Ratio (M‐H, Random, 95% CI) | 1.11 [0.49, 2.49] |
| 16 Freedom from atrial fibrillation, flutter, or tachycardia >3 months (paroxsymal atrial fibrillation only) | 2 | 70 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.54 [1.47, 4.36] |
| 17 Freedom from atrial fibrillation, flutter, or tachycardia >3 months (cut‐and‐sew only) | 4 | 124 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.49 [1.60, 3.87] |
| 18 Freedom from atrial fibrillation, flutter, or tachycardia >3 months (non‐mitral valve surgery only) | 3 | 175 | Risk Ratio (M‐H, Random, 95% CI) | 1.89 [1.41, 2.53] |
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 | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Methods of randomisation not reported |
| Allocation concealment (selection bias) | 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." |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias |
Akpinar 2003.
| 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 | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Methods of randomisation not reported |
| Allocation concealment (selection bias) | 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 | High risk | Relied upon 12‐lead ECG for outcome assessment; blinding of outcome assessors not reported |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | All participants analysed for final outcomes |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias |
Albrecht 2009.
| 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 <18 or >79 years, LVEF < 20%, pregnant, re‐operations, 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 |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Methods of randomisation not reported |
| Allocation concealment (selection bias) | 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. |
| 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 | High risk | Relied upon 12‐lead ECG for outcome assessment; blinding of outcome assessors not reported |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | No losses to follow‐up |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias |
Blomstrom‐Lundqvist 2007.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Block randomisation described; almost certainly used valid randomisation method |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding of participants and personnel (performance bias) All outcomes | 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.” |
| Blinding of outcome assessment (detection bias) All outcomes | 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) |
| Incomplete outcome data (attrition bias) All outcomes | 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 |
| Selective reporting (reporting bias) | High risk | Health‐related quality of life outcomes not reported |
| Other bias | High risk | Small‐study bias |
Budera 2012.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not reported |
| Allocation concealment (selection bias) | Unclear risk | "...after informed consent was obtained, an envelope containing either ‘SA’ or ‘non‐SA’ was opened” ". No mention if envelopes were opaque. |
| Blinding of participants and personnel (performance bias) All outcomes | 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.” |
| Blinding of outcome assessment (detection bias) All outcomes | 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.” |
| Incomplete outcome data (attrition bias) All outcomes | 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) |
| Selective reporting (reporting bias) | Low risk | Protocol available: NCT00665587 |
| Other bias | Low risk | No other risk of biases identified |
Cherniavsky 2014.
| Methods | Randomised controlled, parallel group (1:1:1) trial | |
| 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; (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; (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 |
|
| 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 | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method for sequence generation not reported |
| Allocation concealment (selection bias) | 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.” |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | “Patients participating in the study and the investigators evaluating the outcomes were blinded to group assignment” via implantable loop recorder. |
| Blinding of outcome assessment (detection bias) All outcomes | 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." |
| Incomplete outcome data (attrition bias) All outcomes | 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.” |
| Selective reporting (reporting bias) | Unclear risk | No protocol available and authors did not respond to requests for information. |
| Other bias | High risk | Small‐study bias |
Chevalier 2009.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Central randomisation, likely low risk of bias |
| Allocation concealment (selection bias) | Low risk | Central randomisation |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Participants were blinded (low risk of bias) but personnel were not (high risk of bias) |
| Blinding of outcome assessment (detection bias) All outcomes | 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." |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 100% follow‐up |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias; enrolment lower than planned |
de Lima 2004.
| Methods | 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 |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection 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. |
| Allocation concealment (selection bias) | Unclear risk | As above; no mention of whether or not the envelopes were opaque or not |
| 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 | 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." |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Follow‐up unclear |
| Selective reporting (reporting bias) | High risk | "patients who exhibited recurrent AF were excluded from the follow‐up analyses of the sinus rhythm maintenance” |
| Other bias | High risk | Small‐study bias |
Deneke 2002.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 | Authors' judgement | Support for judgement |
| Random sequence generation (selection 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. |
| Allocation concealment (selection bias) | Unclear risk | 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 |
| Incomplete outcome data (attrition bias) All outcomes | 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).” |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias |
Doukas 2005.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 pacemaker, 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 anti‐arrhythmic drugs. Funding: British Heart Foundation |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | “Randomised blocks of between 4 and 6 were prepared for each subgroup in advance by a computer‐generated numbers...” |
| Allocation concealment (selection bias) | 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” |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Participants were blinded (low risk of bias) but personnel were not (high risk of bias) |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | “assessors of outcomes were blinded to group assignment” |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 100% follow‐up; deaths not included in the primary outcome assessment in the report but included in this analysis |
| Selective reporting (reporting bias) | Low risk | Outcomes match protocol: NCT00238706 |
| Other bias | Low risk | No other risk of biases identified |
Gillinov 2015.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 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 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) 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 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 |
|
| Notes | Funding: National Institutes of Health, Canadian Institutes of Health Research | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection 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 intraoperative trans‐esophageal echocardiography confirmed the absence of a left atrial thrombus. Randomization was stratified according to center." |
| Allocation concealment (selection bias) | Unclear risk | Site of randomisation not reported |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | "Neither patients nor investigators will be blinded to treatment" [protocol] |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | "Those assessing the primary outcome will be blinded to patients' treatment assignment." |
| Incomplete outcome data (attrition bias) All outcomes | 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) |
| Selective reporting (reporting bias) | Low risk | Outcomes match protocol: NCT00238706 and Supplemental Appendix |
| Other bias | Low risk | No other risk of biases identified |
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 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 |
|
| 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 | Authors' judgement | Support for judgement |
| Random sequence generation (selection 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.” |
| Allocation concealment (selection 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.” |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | As above, not blinded and likely high risk of bias for this domain |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | As above, not blinded and likely high risk of bias for this domain |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 100% follow‐up |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias |
Jonsson 2012.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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, 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 |
|
| 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, anti‐arrhythmic 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 | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | “computer‐based randomization was performed by an external resource” |
| Allocation concealment (selection bias) | 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” |
| Blinding of participants and personnel (performance bias) All outcomes | 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). |
| Blinding of outcome assessment (detection bias) All outcomes | 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” |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 1 participant lost to follow‐up and 5 participants died. Not reported why these participants were excluded from baseline and operative analyses. |
| Selective reporting (reporting bias) | High risk | Health‐related quality of life outcomes not reported |
| 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.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Methods of randomisation not reported |
| Allocation concealment (selection bias) | 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 |
| Incomplete outcome data (attrition bias) All outcomes | High risk | “the 12 month follow‐up was complete, although 2 group B [control] patients were unable to revisit our outpatient cardiology clinics” |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Protocol changes throughout manuscript; small‐study bias |
Knaut 2010.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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, LVEF < 30%, stroke in past 3 months, MI in the last 30 days, previous heart operations, necessary LA incision during the surgery, necessary RA incision during the surgery, acute myocarditis, existence of a thrombus in left atrial appendage, heart failure NYHA IV, implanted pacemaker, implanted defibrillator, pregnancy and breast feeding, known drug dependency, unable to provide consent Intervention (n = 24): mean (SD) age: 74 (4.4) years, 42% women, 100% "permanent" AF, mean (SD) AF duration 5.9 (4.4) years, mean ejection fraction 56%, 58% aortic valve replacement, 54% CABG surgery, mean (SD) operative time 173 (NR) minutes Comparator (n = 21): mean (SD) age: 74.8 (5.8) years, 29% women, 100% "permanent" AF, mean (SD) AF duration 4.3 (8) years, mean ejection fraction, 58% aortic valve replacement, 50% CABG surgery, mean (SD) operative time 150 (NR) minutes |
|
| Interventions | Intervention: aortic valve or CABG surgery + left atrial microwave ablation (Guidant Corp. (Santa Clara, CA, USA) microwave surgical ablation device (FLEX4®)) Comparator: aortic valve or CABG surgery + usual care |
|
| Outcomes | Primary outcome: Incidence of sinus rhythm after 30, 90, 180, and 360 days postoperatively Secondary outcome(s): Not reported Mean follow‐up: 12 months Arrhythmia monitoring during follow‐up: clinic visit at 1, 3, 6, and 12 months after surgery; 12‐lead ECG and 24‐hour Holter monitor at 6 and 12 months after surgery |
|
| Notes | Usual care included: From the first postoperative day and continued for at least 6 months, the patients received a conventional beta‐blocker (normally metoprolol) Funding: not reported |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | “After the patients gave informed consent, they were randomly assigned to the therapy group (epicardial microwave ablation) or the control group (equivalent operation without EMW).” Methods of randomisation not reported. |
| Allocation concealment (selection bias) | 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 |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 100% follow‐up |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias |
Pokushalov 2012.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| Participants | 35 adult participants (>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 (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 |
|
| 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 | Authors' judgement | Support for judgement |
| Random sequence generation (selection 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 |
| Allocation concealment (selection bias) | 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 | Low risk | Implantable loop recording outcome assessment “blinded” |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 100% follow‐up |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Study author is industry employee; small‐study bias |
Schuetz 2003.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 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 |
|
| 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 | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Methods of randomisation not reported (asked by audience member in the discussion section but no answer provided) |
| Allocation concealment (selection bias) | 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 |
| Incomplete outcome data (attrition bias) All outcomes | 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 |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias |
Srivastava 2008.
| 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. 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 |
|
| 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 follow‐up, participants in AF were put on oral amiodarone for two months and underwent repeat cardioversion if still in AF. Funding: none |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | “The four groups were labelled as 1, 2, 3 and 4 and a computer‐generated 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” |
| Allocation concealment (selection bias) | Unclear risk | Methods of allocation concealment not reported |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | “Single blind” study; personnel not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | “Single blind” study; outcome assessors not blinded |
| Incomplete outcome data (attrition bias) All outcomes | High risk | High loss to follow‐up throughout and only ECG used for evaluation of recurrent AF |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | Low risk | No other risk of biases identified |
van Breugel 2010.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 and12 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 | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection 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. |
| Allocation concealment (selection bias) | Unclear risk | Method of allocation concealment not reported |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | “Patients and all medical personnel (with exception of the surgical team) were blinded to their group assignment." |
| 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. |
| Incomplete outcome data (attrition bias) All outcomes | 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 |
| Selective reporting (reporting bias) | 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 | No other risk of biases identified |
Vasconcelos 2004.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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: 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 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 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 | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Methods of randomisation not described |
| Allocation concealment (selection bias) | 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 | “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 |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 2/29 participants lost to follow‐up and excluded from analyses |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias |
von Oppell 2009.
| Methods | Randomised controlled, parallel group (1:1) trial | |
| 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 Funding: Medtronic Bakken Research Center |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection 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.” |
| Allocation concealment (selection 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.” |
| Blinding of participants and personnel (performance bias) All outcomes | 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 |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Personnel were not blinded during outcome assessment, which included only 1 Holter monitor per participants at 3 months after surgery |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 100% follow‐up |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | High risk | Small‐study bias; senior author was Medtronic employee |
Wang 2014.
| Methods | Randomised controlled, parallel group (1:1:1) trial | |
| 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 bi‐atrial 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. 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 x 3 months in the intervention groups Funding: China National Center for Cardiovascular Diseases |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | “The random table was generated by the SAS software” |
| Allocation concealment (selection bias) | Unclear risk | Methods of allocation concealment not reported |
| Blinding of participants and personnel (performance bias) All outcomes | 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 |
| Blinding of outcome assessment (detection bias) All outcomes | 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” |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 100% follow‐up reported |
| Selective reporting (reporting bias) | Low risk | Similar outcomes reported in the report compared with the study protocol (NCT01013688) |
| Other bias | Low risk | No other risk of biases identified |
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]
| Study | Reason for exclusion |
|---|---|
| Ailawadi 2011 | Wrong intervention |
| Al Halabi 2015 | Wrong patient population |
| Al‐Atassi 2014 | Wrong patient population |
| Al‐Khatib 2014 | Wrong study design |
| Assasi 2012 | Wrong study design |
| Basu 2012 | Wrong study design |
| Biancari 2010 | Wrong patient population |
| Bockeria 2011 | Wrong study design |
| Breda 2008 | Wrong patient population |
| 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 | Wrong patient population |
| 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 |
| 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.
| 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 hanjs0216@sina.com Retrospective registration Status: unknown Reason: no response to email requests for information |
NCT00735722.
| 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 United Kingdom Email: sridolfo@nhs.net (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 | Trial name: Surgical Pulmonary Vein Isolation Efficiency Study (FIN‐PVI, NCT01791218) Starting date: November 2012 Contact information: Teemu Riekkinen Kuopio University Hospital 358044175527 teemu.riekkinen@kuh.fi 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.
| 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 | |
| Starting date | September 2013 |
| Contact information | Dr. Farkas Vánky Dept. of Cardiothoracic and Vascular Surgery University Hospital Linköping (Sweden) farkas.vanky@lio.se |
| 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 |
| 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 jane.fisher@papworth.nhs.uk |
| Notes | Expected study completion date: July 2017 No response to email requests for information |
NCT01360918.
| 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 |
| Outcomes | |
| Starting date | September 2005 |
| Contact information | Bob Oude Velthius, MD, MSc Medisch Spectrum Twente b.oudevelthius@mst.nl |
| 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 |
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 | |
| Starting date | 23 July 2012 |
| Contact information | Antoine Da Costa, MD, PhD Centre Hospitalier Universitaire de Saint Etienne antoine.dacosta@univ‐st‐etienne.fr |
| 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 (SANMORITZ 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 |
| Outcomes | |
| Starting date | 6 January 2015 |
| Contact information | Takashi Kunihara The Cardiovascular Institute Division of Cardiovascular Surgery Tokyo kunihara@cvi.or.jp |
| 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
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 anti‐arrhythmic 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.
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.
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.
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. Boehringer Ingelheim, AstraZeneca, and Bupa had no input or influence over the grants’ nominations, the World Heart Federation controlled the use of the funds.
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.
Edited (no change to conclusions)
References
References to studies included in this review
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de Lima 2004 {published data only}
- 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. [DOI] [PubMed] [Google Scholar]
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Schuetz 2003 {published data only}
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References to studies excluded from this review
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Al‐Khatib 2014 {published data only}
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Cheng 2010 {published data only}
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Damiano 2003 {published data only}
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DECIT‐CGATS 2009 {published data only}
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Deneke 2001 {published data only}
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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; Vol. 110 (17):692.
Dunning 2013 {published data only}
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Healey 2005 {published data only}
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Kong 2010 {published data only}
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Lins 2010 {published data only}
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Nagpal 2009 {published data only}
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NICE 2005 {published data only}
- National Institute for Clinical Excellence. Radiofrequency ablation for atrial fibrillation in association with other cardiac surgery. NICE interventional procedure guidance, Report No. IPG121. London: National Institute for Clinical Excellence (NICE), 2005:245.
NICE 2005a {published data only}
- National Institute for Clinical Excellence. Microwave ablation for atrial fibrillation in association with other cardiac surgery. NICE interventional procedure guidance, Report No. IPG122. London: National Institute for Clinical Excellence (NICE), 2005:266.
NICE 2005b {published data only}
- National Institute for Clinical Excellence. Cryoablation for atrial fibrillation in association with other cardiac surgery. NICE interventional procedure guidance, Report No. IPG123. London: National Institute for Clinical Excellence (NICE), 2005:271.
NICE 2006 {published data only}
- National Institute for Health and Clinical Excellence. High‐intensity focused ultrasound for atrial fibrillation in association with other cardiac surgery. NICE interventional procedure guidance, Report No. IPG184. London: National Institute for Health and Clinical Excellence (NICE), 2006:312.
NICE 2010 {published data only}
- National Institute of Health and Care Excellence. Thoracoscopic epicardial radiofrequency ablation for atrial fibrillation. NICE interventional procedure guidance, Report No. IPG286. Seoul: Committee for New Health Technology Assessment (CNHTA), 2010:IP 716.
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Phan 2014 {published data only}
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Tsai 2015 {published data only}
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Whitlock 2013 {published data only}
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References to studies awaiting assessment
ChiCTR‐TRC‐07003039 {unpublished data only}
- ChiCTR‐TRC‐07003039. 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 (accessed 6 May 2016).
NCT00735722 {unpublished data only}
- NCT00735722. A(f)MAZE‐CABG Study (AFMAZE‐CABG). clinicaltrials.gov/ct2/show/NCT00735722 (accessed 6 May 2016).
NCT01791218 {unpublished data only}
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References to ongoing studies
ISRCTN14454361 {unpublished data only}
- ISRCTN14454361. 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). www.isrctn.com/ISRCTN14454361 (accessed 6 May 2016).
ISRCTN82731440 {unpublished data only}
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NCT01360918 {unpublished data only}
- NCT01360918. Concomitant epicardial pulmonary vein isolation in patients with AF undergoing elective cardiac surgery (CONTROL‐AF). clinicaltrials.gov/ct2/show/NCT01360918 (accessed 6 May 2016).
NCT01649544 {unpublished data only}
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