Concomitant atrial fibrillation surgery for people undergoing cardiac surgery
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.
PICOs
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.
Authors' conclusions
Summary of findings
| Concomitant atrial fibrillation surgery for people undergoing cardiac surgery | |||||
| Patient or population: individuals with atrial fibrillation who are undergoing cardiac surgery | |||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | |
| Risk with no atrial fibrillation surgery | Risk with concomitant atrial fibrillation surgery | ||||
| All‐cause mortality | Study population | RR 1.14 | 1829 | ⊕⊕⊝⊝ | |
| 66 per 1000 | 75 per 1000 | ||||
| Freedom from AF/AFL/AT off antiarrhythmic medications > 3 months | Study population | RR 2.04 | 649 | ⊕⊕⊕⊝ | |
| 241 per 1000 | 492 per 1000 | ||||
| Investigator‐defined adverse events | Study population | RR 1.07 | 858 | ⊕⊝⊝⊝ | |
| 236 per 1000 | 252 per 1000 | ||||
| Pacemaker implantation4 | Study population | RR 1.69 | 1726 | ⊕⊕⊕⊝ | |
| 41 per 1000 | 69 per 1000 | ||||
| 30‐day mortality4 | Study population | RR 1.25 | 1566 | ⊕⊕⊝⊝ | |
| 23 per 1000 | 29 per 1000 | ||||
| *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). | |||||
| GRADE Working Group grades of evidence | |||||
| 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
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All‐cause mortality
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Freedom from atrial fibrillation, flutter, or tachycardia off antiarrhythmic medications, as measured by patient electrocardiographic monitoring greater than three months after the procedure
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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
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Cardiovascular mortality
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Fatal and non‐fatal cardiovascular events, including myocardial infarction, stroke, transient ischaemic attack, or heart failure
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Freedom from atrial fibrillation
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30‐day rehospitalisation
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Need for post‐discharge direct current cardioversion
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Health‐related quality of life measured by any validated and adjusted scale concerning quality of life
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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:
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Cochrane Library (Wiley)
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Cochrane Database of Systematic Reviews: Issue 3 of 12, March 2016
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Cochrane Central Register of Controlled Trials (CENTRAL): Issue 2 of 12, February 2016
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Database of Abstracts of Reviews of Effect (DARE): Issue 2 of 4, April 2015
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Health Technology Assessment Database (HTA): Issue 1 of 4, January 2016
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Ovid MEDLINE(R) 1946 to March Week 4 2016
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Ovid MEDLINE(R) In‐Process & Other Non‐Indexed Citations March 30, 2016
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Embase 1974‐present; Embase Classic 1947‐1973; MEDLINE 1966‐present (embase.com)
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Conference Proceedings Citation Index‐Science (CPCI‐S) 1990‐present (Web of Science)
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ClinicalTrials.gov (searched 1 April 2016)
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World Health Organization International Clinical Trials Registry Platform (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).
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.
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Random sequence generation (selection bias)
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Allocation concealment (selection bias)
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Blinding of participants and personnel (performance bias) and of outcome assessors (detection bias)
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Incomplete outcome data (attrition bias)
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Selective reporting (reporting bias)
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Other potential sources of bias
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”.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'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 summary of findings Table for the main comparison based on the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We present results on the outcomes as described in the Types of outcome measures section.
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.
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Paroxysmal versus persistent AF (paroxysmal AF studies defined post‐hoc as including ≥ 50% of participants)
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Type of AF surgery (cut‐and‐sew versus radiofrequency ablation)
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Type of cardiac surgery (mitral versus non‐mitral cardiac surgery)
Sensitivity analysis
We had proposed performing sensitivity analyses to explore the influence of the following factors on effect sizes.
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Restricting the analysis to published studies
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Restricting the analysis by taking into account risk of bias, as specified in the Assessment of risk of bias in included studies section
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Restricting the analysis to very long (> five years) or large (> 500 participants) studies to establish the extent to which they dominate the results
However, we were unable to complete this sensitivity analysis because we did not have data for unpublished studies; all but one (Doukas 2005) of the identified studies were assessed as having high or unclear risk of bias across two or more domains, and there were no studies with follow‐up > five years or with > 500 participants.
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 1 summarises the included studies. Trials were reported between 2001 and 2015. Most (17/22) trials were small (< 200 participants) and were performed in a single centre or country, including nine trials in low‐ or middle‐income countries. The mean age in each arm ranged from 36 years (Srivastava 2008) to 75 years (Knaut 2010), and the proportion of women in each arm ranged from 16% (Jonsson 2012) to 73% (Vasconcelos 2004). Only two trials (Pokushalov 2012; Vasconcelos 2004) included only participants with paroxysmal atrial fibrillation (AF), and only two trials did not have a majority of participants undergoing mitral valve surgery (Knaut 2010; Pokushalov 2012) with a high proportion of rheumatic heart disease present in most trials. Three trials used a cut‐and‐sew technique (Albrecht 2009; Jessurun 2003; Vasconcelos 2004), three trials used a microwave ablation technique (Jonsson 2012; Knaut 2010; Schuetz 2003), two trials exclusively used cryoablation (Blomstrom‐Lundqvist 2007; Budera 2012), and the remaining trials used either monopolar or bipolar radiofrequency ablation.
| Study | Country | N | Primary cardiac surgery | Intervention | Longest follow‐up (months) | Outpatient arrhythmia monitoring | |||
| Technique | RA | LA | PVI | ||||||
| Brazil | 70 | MV | RF | X | X | X | 12 | ECG at each clinic visit; 24‐hr Holter at 3, 6, 12 months | |
| Turkey | 67 | MV | RF | * | X | 18 | ECG at 6, 12, > 12 months | ||
| Brazil | 60 | MV | Cut‐and‐sew | X | X | X | 60 | ECG and ETT every 6 months | |
| Sweden | 65 | MV | Cryo | X | X | 12 | ECG at 1, 2, 3, 6, 12 months | ||
| 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) | ||
| Russia | 95 | CABG | RF | X | X | X | 24 | ILR data collection at 3, 6, 24 months | |
| France | 43 | MV | RF | X | X | 12 | ECG and 24‐hr Holter at discharge, 3, and 12 months | ||
| 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 | |
| Germany | 30 | MV | RF | X | X | X | 12 | ECG at 3, 6, 9, and 12 months; 24‐hr Holter at 6, 12 months | |
| 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 | ||
| USA, Canada | 260 | MV | Cryo ± RF | X | X | X | 12 | 72‐hr Holter at 6, 12 months | |
| Netherlands | 35 | MV | Cut‐and‐sew | X | X | X | 12 | ECG at 3, 12 months; 24‐hr Holter at 3, 12 months | |
| 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 | |
| Germany | 30 | MV | (Cut and sew) RF intraatrial lesions | X | X | X | 12 | ECG and 24‐hr Holter at 6, 12 months | |
| Germany | 45 | CABG, AV | Microwave | X | 12 | ECG and 24‐hr Holter at 6, 12 months | |||
| Russia | 35 | CABG | RF | X | 18 | ILR data collection at 1, 3, 6, 9, 12, 18 months | |||
| Germany | 43 | CABG, MV, TV, AV | Microwave | X | X | 12 | ECG and 24‐hr Holter at 3, 6, 12 months | ||
| India | 160 | MV | Cryo or RF | X | X | X | 60 | ECG every 3 months | |
| Netherlands | 150 | MV ± CABG | Microwave | X | X | 12 | ECG at 3, 6, 12 months; 24‐hr Holter at 12 months | ||
| Brazil | 29 | MV | Cut‐and‐sew | X | 24 | ECG, “portable device” ‐ time frame not reported | |||
| UK | 49 | MV | RF | X | X | X | 12 | ECG at 3, 12 months; 24‐hr Holter at 3 months | |
| 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.
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.
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
Key results are reported in the summary of findings Table for the main comparison, including overall results related to adverse events and specific outcomes related to procedural safety. Analyses 1‐18 (Analysis 1.1; Analysis 1.2; Analysis 1.3; Analysis 1.4; Analysis 1.5; Analysis 1.6; Analysis 1.7; Analysis 1.8; Analysis 1.9; Analysis 1.10; Analysis 1.11; Analysis 1.12; Analysis 1.14; Analysis 1.15; Analysis 1.16; Analysis 1.17; Analysis 1.18) describe the forest plots for the effects of concomitant cardiac surgery on various outcomes. When trials had multiple intervention groups (Albrecht 2009, de Lima 2004), we combined these groups to estimate the general effect of atrial fibrillation (AF) surgery.
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).
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.
PRISMA flow chart of included studies.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
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.
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.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 1 All‐cause mortality.
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.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 3 Freedom from atrial fibrillation, atrial flutter, or atrial tachycardia.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 4 Adverse events as defined by investigators.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 5 Permanent pacemaker implantation.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 6 30‐day mortality.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 7 Mediastinitis.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 8 Cardiac tamponade.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 9 Neurologic or thromboembolic events.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 10 Need for surgical re‐exploration.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 11 Cardiovascular mortality.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 12 Fatal and nonfatal cardiovascular events.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 13 Freedom from atrial fibrillation.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 14 30‐day rehospitalisation.
Comparison 1 Atrial fibrillation surgery versus no atrial fibrillation surgery, Outcome 15 Need for post‐discharge direct current cardioversion.
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).
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).
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).
| Concomitant atrial fibrillation surgery for people undergoing cardiac surgery | |||||
| Patient or population: individuals with atrial fibrillation who are undergoing cardiac surgery | |||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | |
| Risk with no atrial fibrillation surgery | Risk with concomitant atrial fibrillation surgery | ||||
| All‐cause mortality | Study population | RR 1.14 | 1829 | ⊕⊕⊝⊝ | |
| 66 per 1000 | 75 per 1000 | ||||
| Freedom from AF/AFL/AT off antiarrhythmic medications > 3 months | Study population | RR 2.04 | 649 | ⊕⊕⊕⊝ | |
| 241 per 1000 | 492 per 1000 | ||||
| Investigator‐defined adverse events | Study population | RR 1.07 | 858 | ⊕⊝⊝⊝ | |
| 236 per 1000 | 252 per 1000 | ||||
| Pacemaker implantation4 | Study population | RR 1.69 | 1726 | ⊕⊕⊕⊝ | |
| 41 per 1000 | 69 per 1000 | ||||
| 30‐day mortality4 | Study population | RR 1.25 | 1566 | ⊕⊕⊝⊝ | |
| 23 per 1000 | 29 per 1000 | ||||
| *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). | |||||
| GRADE Working Group grades of evidence | |||||
| 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. | |||||
| Study | Country | N | Primary cardiac surgery | Intervention | Longest follow‐up (months) | Outpatient arrhythmia monitoring | |||
| Technique | RA | LA | PVI | ||||||
| Brazil | 70 | MV | RF | X | X | X | 12 | ECG at each clinic visit; 24‐hr Holter at 3, 6, 12 months | |
| Turkey | 67 | MV | RF | * | X | 18 | ECG at 6, 12, > 12 months | ||
| Brazil | 60 | MV | Cut‐and‐sew | X | X | X | 60 | ECG and ETT every 6 months | |
| Sweden | 65 | MV | Cryo | X | X | 12 | ECG at 1, 2, 3, 6, 12 months | ||
| 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) | ||
| Russia | 95 | CABG | RF | X | X | X | 24 | ILR data collection at 3, 6, 24 months | |
| France | 43 | MV | RF | X | X | 12 | ECG and 24‐hr Holter at discharge, 3, and 12 months | ||
| 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 | |
| Germany | 30 | MV | RF | X | X | X | 12 | ECG at 3, 6, 9, and 12 months; 24‐hr Holter at 6, 12 months | |
| 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 | ||
| USA, Canada | 260 | MV | Cryo ± RF | X | X | X | 12 | 72‐hr Holter at 6, 12 months | |
| Netherlands | 35 | MV | Cut‐and‐sew | X | X | X | 12 | ECG at 3, 12 months; 24‐hr Holter at 3, 12 months | |
| 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 | |
| Germany | 30 | MV | (Cut and sew) RF intraatrial lesions | X | X | X | 12 | ECG and 24‐hr Holter at 6, 12 months | |
| Germany | 45 | CABG, AV | Microwave | X | 12 | ECG and 24‐hr Holter at 6, 12 months | |||
| Russia | 35 | CABG | RF | X | 18 | ILR data collection at 1, 3, 6, 9, 12, 18 months | |||
| Germany | 43 | CABG, MV, TV, AV | Microwave | X | X | 12 | ECG and 24‐hr Holter at 3, 6, 12 months | ||
| India | 160 | MV | Cryo or RF | X | X | X | 60 | ECG every 3 months | |
| Netherlands | 150 | MV ± CABG | Microwave | X | X | 12 | ECG at 3, 6, 12 months; 24‐hr Holter at 12 months | ||
| Brazil | 29 | MV | Cut‐and‐sew | X | 24 | ECG, “portable device” ‐ time frame not reported | |||
| UK | 49 | MV | RF | X | X | X | 12 | ECG at 3, 12 months; 24‐hr Holter at 3 months | |
| 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 | |||||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality Show forest plot | 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 Show forest plot | 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 Show forest plot | 22 | 1899 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.46 [2.16, 2.80] |
| 4 Adverse events as defined by investigators Show forest plot | 9 | 858 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [0.85, 1.34] |
| 5 Permanent pacemaker implantation Show forest plot | 18 | 1726 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.69 [1.12, 2.54] |
| 6 30‐day mortality Show forest plot | 18 | 1566 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.25 [0.71, 2.20] |
| 7 Mediastinitis Show forest plot | 3 | 290 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.49 [0.24, 9.12] |
| 8 Cardiac tamponade Show forest plot | 3 | 166 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.34 [0.07, 1.67] |
| 9 Neurologic or thromboembolic events Show forest plot | 14 | 1155 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.60, 1.83] |
| 10 Need for surgical re‐exploration Show forest plot | 9 | 929 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.58, 1.91] |
| 11 Cardiovascular mortality Show forest plot | 9 | 496 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.82 [0.72, 4.60] |
| 12 Fatal and nonfatal cardiovascular events Show forest plot | 8 | 826 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.17 [0.86, 1.59] |
| 13 Freedom from atrial fibrillation Show forest plot | 15 | 1500 | Risk Ratio (M‐H, Random, 95% CI) | 2.55 [2.01, 3.24] |
| 14 30‐day rehospitalisation Show forest plot | 1 | 260 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [1.06, 1.75] |
| 15 Need for post‐discharge direct current cardioversion Show forest plot | 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) Show forest plot | 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) Show forest plot | 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) Show forest plot | 3 | 175 | Risk Ratio (M‐H, Random, 95% CI) | 1.89 [1.41, 2.53] |
