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Introduction
Left atrial appendage exclusion (LAAE) has been shown in randomized trials to reduce ischemic stroke risk in patients undergoing cardiac surgery with known atrial fibrillation (AF). Many patients undergoing cardiac surgery without pre-existing AF are at risk of stroke and may benefit from LAAE.
MethodsLeft Atrial Appendage Exclusion for Prophylactic Stroke Reduction (LeAAPS) is an international, prospective, randomized, multicenter, blinded trial evaluating the effectiveness of LAAE in preventing ischemic stroke or systemic embolism in patients undergoing cardiac surgery at increased risk of AF and ischemic stroke. The trial will enroll 6500 patients at increased risk of stroke in whom a cardiac surgery is planned at 250 sites worldwide. Eligible patients are ≥18 years old, have no pre-existing AF but are at increased risk for AF and stroke (based on age, CHA
The results of the LeAAPS trial will demonstrate whether LAAE with AtriClip at the time of other routine cardiac surgery reduces stroke or systemic arterial embolism during long-term follow-up in patients at high risk of stroke without pre-existing AF.
Trial RegistrationClinicalTrials.gov, Identifier: NCT05478304,
Atrial fibrillation (AF) affects 1% to 2% of the general population 1 and is associated with a 5-fold higher risk of stroke compared with individuals without AF. 2 Multiple studies over several decades have shown that 90% of cardioembolic strokes in patients with AF are from thrombi situated in the left atrial appendage (LAA). 3 Oral anticoagulation reduces embolic stroke in patients with AF by two-thirds and is recommended for most patients with AF; 4 however, long-term effectiveness is mitigated by temporary and permanent discontinuation, 5-7 and nonadherence/noncompliance with dosing regimens. 5 , 7-11 A retrospective study of >60,000 patients found that only 47.5% of direct oral anticoagulant users remained adherent by 1 year. 7 Reasons for this include cost, side-effect profile (ie, dyspepsia), professional hazards (ie, using sharp instruments, machines, or vehicles), fall risk, advanced age, dementia (ie, cerebral amyloid angiopathy/microbleeds) and other bleeding diatheses/conditions (ie, thrombocytopenia, cancer, etc). 8 Therefore, additional options that compensate for the panoply of shortcomings of oral anticoagulation are needed.
Approximately 2 million people undergo cardiac surgery each year globally, and conservatively, an estimated 10% have pre-existing AF. 12 Surgical LAA exclusion (LAAE) during cardiac surgery has been shown to reduce stroke risk in patients with preexisting AF independent of oral anticoagulation. 13-15 In 2021, the randomized Left Atrial Appendage Occlusion Study (LAAOS) III trial demonstrated that in patients undergoing cardiac surgery with preexisting AF, surgical LAAE lowered the risk of stroke or systemic embolism by 33% over 3.8 years of follow-up on top of oral anticoagulation. 13 One of the methods of surgical LAAE in LAAOS III was the AtriClip LAA exclusion device, which was used in approximately 15% of the trial patients. The LAAOS III results were limited to patients who already had AF, whereas most patients undergoing cardiac surgery do not have AF. However, many patients undergoing cardiac surgery have substantial risk factors for both developing AF and for stroke. Therefore, we designed the Left Atrial Appendage Exclusion for Prophylactic Stroke Reduction (LeAAPS) trial, with the objective of evaluating the effectiveness of LAAE with AtriClip for the prevention of ischemic stroke or systemic arterial embolism in patients undergoing cardiac surgery who are at high-risk for both developing AF and for ischemic stroke. 16
MethodsThe LeAAPS trial is an international, prospective, randomized, multicenter, blinded superiority, investigational device exemption trial (ClinicalTrials.gov Identifier: NCT05478304). Planned enrollment is approximately 6500 patients at up to 250 centers worldwide over the course of 4 years. All patients are followed for a minimum of 5 years irrespective of when the primary analysis is performed. The expected duration of the trial is approximately 9 years.
Inclusion and exclusion criteriaEligible patients must be ≥18 years of age, with planned and clinically indicated cardiac surgical procedure requiring opening of the pericardium and have documentation of an elevated risk of stroke as demonstrated by criteria listed in Table 1 . Exclusion criteria include any documented history of clinically significant AF or atrial flutter (ie, documented episodes ≥6 minutes); prior procedure involving opening the pericardium or entering the pericardial space; prior LAA occlusion, exclusion, or removal (surgical or percutaneous); or planned cardiac surgical procedure using nonsternotomy approaches. The complete exclusion criteria are listed in Table 1.
RandomizationPatients are randomized 1:1 to receive either LAAE or no LAAE at the time of planned cardiac surgery using a central randomization list stratified by center and in randomly permuted blocks of undisclosed size. Randomization is completed using a secure central website located at the Population Health Research Institute (Hamilton, On, CA). Randomization occurs as close to the start of surgery as feasible.
BlindingParticipating surgeons have implanted a minimum of 5 AtriClips and are reviewed and approved by a clinical specialist from the sponsor. The surgeon and operating room personnel are not blinded, but every effort is made to ensure the treatment assignment is not revealed to patients, trial personnel, and other clinicians caring for the patient outside of the operating room. The operative report and dictated surgical report will only indicate that the patient has been enrolled into the LeAAPS randomized trial and may or may not have received LAAE.
Patients in both arms receive usual standard of care, including oral anticoagulation, in the event they develop postoperative AF. The clinicians are to use guideline-directed oral anticoagulation per their institutional standard of care. It is imperative that the clinicians making decisions regarding anticoagulation for AF remain blinded, and that this decision not be biased by knowledge of trial allocation. If a patient develops transient AF prior to hospital discharge, local standard of care for oral anticoagulant use are followed as if the LAA was not excluded, irrespective of randomized treatment assigned and received.
Trial flow and assessment scheduleThe trial flow is shown in Figure 1 and schedule of events and visits is included in Table 2 . Patients in the device arm receive LAAE with the AtriClip LAA Exclusion System (Mason, OH, USA) per the device Instructions for Use at the time of planned cardiac surgery. AtriClip is a nonabsorbable permanent implant that is designed to permanently exclude and electrically isolate the LAA from the left atrium, but without amputating the LAA. The excluded tissue heals normally at the site of the approximation and atrophies distal to the device. When LAAE is performed, transesophageal echocardiogram intraoperatively will confirm successful LAA exclusion, defined as absence of leaks between the left atrium and LAA and lack of residual stump <10 mm. Patients in the control arm will not receive LAAE at the time of planned cardiac surgery.
Patients are followed for a minimum of 5 years irrespective of when the primary analysis is performed. The trial will be event-driven, meaning that follow-up will continue until 469 patients have an ischemic stroke or systemic embolism, the necessary number of events for planned statistical power for both the primary and powered secondary effectiveness endpoints. Follow-up visits at 30 days, 6 months, and every 6 months thereafter until final trial visit are performed in person or remotely via telemedicine appointments to complete the required assessments.
EffectivenessThe primary effectiveness endpoint is the first occurrence of ischemic stroke or systemic arterial embolism or any procedure wherein the LAA was excluded, occluded, or amputated following the index procedure over the duration of follow-up. The powered secondary effectiveness endpoint is the first occurrence of ischemic stroke or systemic embolism (Supplementary 1).
SafetyThe primary safety endpoint is the occurrence of at least one of the following events through 30 days postindex procedure: pericardial effusion requiring percutaneous or surgical treatment, major bleeding attributable to index surgical procedure (modified Bleeding Academic Research Consortium [BARC] type 4 bleeding 17), deep sternal wound infection, or myocardial infarction. The following procedural parameters will also be analyzed: cardiopulmonary bypass time, cross-clamp time, index procedure surgical time (time in the operating room), and chest tube output until chest tube removed or 24 hours postoperatively (whichever is earlier) (Supplementary 1).
All device deficiencies/malfunctions of the AtriClip device will be documented throughout the clinical investigation.
Statistical power and methodsWith enrollment of approximately 6500 patients, the study is estimated to have at least 84% power to detect 25% relative reduction in both the primary and powered secondary effectiveness endpoints.
The sample size estimate was based on the number of patients needed to have sufficient power to detect important change in both the primary effectiveness analysis and the powered secondary effectiveness endpoint analysis. As data are collected in LeAAPS and the aggregate event rate across the groups is better understood, sample size modifications may be considered. The trial is event-driven meaning that follow-up will continue until 469 patients have had an ischemic stroke or systemic embolism. The estimate of the rate of ischemic stroke or systemic embolism was arrived at based on several studies that reported stroke rates after cardiac surgery as described in Table 3 . The LAAOS III estimates account for the competing risk of death. The rate of lost to follow-up is estimated to be 2% overall and the rate of cross-over between treatments is estimated to be 3% (this cross-over can only occur at the time of index surgery).
The primary analysis population includes all patients who are randomized and undergo cardiac surgery regardless of treatment received. Kaplan-Meier estimates of cumulative risk and Nelson-Aalen estimates of the cumulative hazard functions will be provided to evaluate the timing of event occurrence in the different treatment groups and the consistency of the respective treatment effects for all time points. The Χ 2 statistic from the Cox proportional model will be used to test the significance of effect. A 2-sided P-value of <.05 for the unadjusted hazard ratio will be considered as significant. The proportional hazards assumption will be verified.
The primary safety endpoint is a composite of potential surgical complications occurring in the perioperative period. The rate of occurrence of this composite endpoint is estimated to be 12% based on the literature. 18-21 The study will therefore have 84% power to demonstrate noninferiority for the primary safety endpoint with the use of the intervention. This will be tested by comparing the rates of primary safety endpoint in the 2 study arms using a noninferiority approach (one-sided P-value of .025) to show that the absolute increase in the primary safety endpoint is less than 2.4% (or relative increase of 20%). This analysis will be conducted on a per-protocol basis. The noninferiority margin is clinically reasonable based on an assessment of risk-benefit. The goal is to demonstrate a 25% relative decrease in the rate of ischemic stroke or systemic embolism, events that are often fatal or disabling. 22-24 Compared to recent trials in patients with AF in which up to 50% of strokes were disabling, 22-24 a possible relative increase of 20% in surgical complications, which only rarely result in death or permanent disability, appears to be reasonable and clinically acceptable. The analysis of the primary safety endpoint will be performed on a per patient basis (patients will be considered to have a primary safety event if they have one or more primary safety event during the 30-day postoperative period). The occurrence of multiple events in individual patients also will be reported separately.
Informed consent and trial ethicsThe LeAAPS trial adheres to all principles and guidelines found within the Declaration of Helsinki, applicable Good Clinical Practices, and appropriate local legislation. Conduct of the clinical investigation is approved by each institution's Institutional Review Board/ Ethics Committee (IRB/EC) and by the applicable regulatory authority. Written inform consent is obtained from all participating patients.
Steering committee, clinical events committee, and data safety monitoring boardThe Steering Committee is responsible for overseeing the scientific and operational aspects of the clinical investigation and is comprised of the trial principal investigator, national leaders of the trial, and sponsor scientists with clinical and methodological expertise. Other advisors with specialized expertise such as stroke neurology are also included.
The Clinical Events Committee (CEC) is an independent, blinded adjudication body comprised of qualified physicians who are not participants in the clinical investigation. The CEC reviews and adjudicates the primary and secondary safety and effectiveness endpoints.
An independent, unblinded Data Safety Monitoring Board (DSMB) regularly reviews patient effectiveness and safety data. The DSMB may make a recommendation to the sponsor and the Steering Committee for modifications or termination of the clinical investigation based on greater than expected efficacy or perceived safety concerns (regardless of statistical significance in the case of safety) considering the balance of benefit and risk. Prespecified thresholds have been set for any 1 of 2 prespecified interim analyses using a modified Haybittle Peto approach. The thresholds for potential termination of the trial for effectiveness will be reductions in the primary endpoint event rate, in favor of the intervention, of ≥ 4 standard deviations (SD) at the first interim analysis and of ≥ 3 SD at the second analysis. The interim analyses will occur when 50% and 75% of the expected primary endpoint events have accumulated.
DiscussionLeAAPS is an international, prospective, randomized, multicenter, blinded trial that will test whether prophylactic exclusion of the LAA reduces ischemic stroke or systemic embolism in patients without a clinical history of AF or preexisting AF undergoing cardiac surgery who have risk factors for both AF and for ischemic stroke. The trial has more than 80% power to detect a 25% reduction in stroke or systemic embolism. Based on the literature, the rate of ischemic stroke or systemic embolism in the LeAAPS trial population is estimated to be 8.7% over a 5-year mean follow-up. A 25% reduction in stroke will prevent 2.2 strokes or systemic emboli per 100 patients treated with LAAE. In contrast, the increased risk of complications with the LAAE is low. Based on these considerations, the risk benefit assessment appears favorable. Further, the long-term follow-up of the LAACS trial suggests that left atrial appendage closure as an add-on to open-heart surgery, regardless of presurgery atrial fibrillation and oral anticoagulation status, may reduce cerebrovascular events. The authors conclude that more extensive randomized clinical trials investigating left atrial appendage closure in patients without atrial fibrillation and high stroke risk are warranted. 25 There are several other trials investigating the effect of LAA closure in patients without a history of atrial fibrillation. 26 , 27 As of May 22nd, 2024, 2421 patients have been enrolled in the LeAAPS trial.
Choice of populationIt is well established that electrical and structural remodeling of the left atrium precedes the development of clinical AF by many years in many patients, and this remodeling can be readily detected clinically by echocardiographic and laboratory biomarkers. This electrical and structural remodeling of the atrium is now termed “atrial cardiomyopathy” or “atriopathy,” which is recognized as a precursor of clinical AF. Heart rhythm societies have defined and characterized atrial cardiomyopathy as “any complex of structural, architectural, contractile or electrophysiological changes affecting the atria with the potential to produce clinically-relevant manifestations.” 28 Diseases such as hypertension, diabetes, valve dysfunction and, in general, aging itself, predispose to atrial cardiomyopathy, with similar pathological changes that progress with time. Atrial cardiomyopathy without clear occurrence of AF is often present in patients undergoing cardiac surgery given the overlap in risk factors for both.
Two of the markers of atrial cardiomyopathy that can be observed prior to cardiac surgery are echocardiographic left atrial enlargement and serum NT-proBNP elevation. These markers are cardinal features of atrial cardiomyopathy, and both are associated with both the development of AF and of stroke, in a directly proportional manner. 29-33
Left atrial enlargement—a predictor of both AF and stroke
Tsang et al. demonstrated that left atrial enlargement is a strong predictor of incident AF. 29 Patients in the highest quartile of left atrial size in a Mayo clinic cohort had a risk of developing AF more than 4 times greater than patients in the lowest quartile. In another cohort of 32,454 Canadian patients, aged 65 years or older, each 10 mm increase in left atrial diameter was associated with 87% increase in the risk for stroke at 5 years, even after adjusting for the competing risk of death and incident AF. 30
NT proBNP— a predictor of both AF and stroke
NT-proBNP is a biomarker that is associated with the development of AF. Serum NT-proBNP levels are associated with both prevalent and incident AF. Patients in the highest quintile of NT-proBNP have a 5.2 fold increased risk for the development of AF compared with the lowest quintile (95% confidence interval, 4.3 to 6.4; P < .001). 31 In this study, NT-proBNP was a very strong predictor of incident AF after adjusting for all important covariates. The adjusted hazard ratio was 4.0 (95% confidence interval, 3.2 to 5.0; P<0.001). Additionally, multiple publications have cited elevated NT-pro BNP as a predictor of cardioembolic strokes. 32 , 33 The 5-year stroke rate is approximately 10% in this high-risk group.
Using these echocardiographic and biomarker predictors a substantial group of patients coming to cardiac surgery who do not yet have AF but who have a high risk of developing AF can be identified. These markers of atrial cardiomyopathy also predict an increase in their risk of stroke in the years following surgery, even without the development of AF. 30 , 32 , 33 Thus, LeAAPS will help evaluate the possibility that it is atrial cardiomyopathy that increases the risk of stroke and whether the risk of stroke is predicated on the development of AF.
Two additional risk factors that will aid in identifying patients at high risk of developing AF and stroke are age and CHA 2DS 2-VASc score.
Age—a predictor of both AF and stroke
Age is a well-established risk factor for AF. Age is an independent predictor of the incidence of postoperative AF after cardiac surgery, with >40% of patients above 70 years of age developing POAF. 34 Additionally, Leitch et al. demonstrated that the prevalence of AF after cardiac surgery was directly related to age at the time of operation, with ∼28% of patients 70 years and above developing AF over time. 35 Age is also a nonmodifiable predictor of stroke with 88% of global strokes occurring above age 65 years, and 72% of which are in those >75 years in patients with or without AF. 36
CHA 2DS 2-VASc—a predictor of both AF and stroke
CHA 2DS 2-VASc is another important risk factor for AF. In a population-based study of 75,000 patients who had diagnosis of AF, the prevalence of AF increased in a graded manner across CHA 2DS 2-VASc score ranging from 1.0% to 49.2% for the scores from 1 to 9. 37 Notably, Healey et al. showed that when the risk factors age, CHA 2DS 2-VASc score, and atrial cardiomyopathy (left atrial enlargement) were combined, the incidence of AF (>5 minutes) was >35% through just 1.5 years. 38 In non-AF cardiac surgery patients with low (0-1), high (2-4), and very high (5-9) CHA 2DS 2-VASc scores, stroke or TIA at 5 years were 5.2%, 14%, and 21.9%; and at 10 years were 5.2%, 20.7%, and 37.9%, respectively. 39 CHA 2DS 2-VASc helps independently identify patients with increased risk of stroke, irrespective of preoperative or new-onset in-hospital AF. 39
At the time of cardiac surgery there is a unique opportunity to perform LAAE at very low risk. During cardiac surgery procedures, the LAA is typically exposed and is readily accessible; there is an opportunity to perform LAAE with minimal complications. The AtriClip device is an epicardial LAA closure device that has 510(k) clearance (K210293) and has been implanted in greater than 550,000 patients. The AtriClip has an excellent LAA exclusion success rate, with complete exclusion, defined as absence of stump and leak between the LAA and LA, reported between 96% to 100%. 40 , 41 Because of its demonstrated low risk of complications and high LAA exclusion rates, the AtriClip is well suited for use in this randomized trial of LAA exclusion in patients who are at risk of developing atrial fibrillation and stroke. The ATLAS trial of 562 patients demonstrated that surgical LAAE with an epicardial clip device (AtriClip) was feasible and safe. 42 , 43 That trial did suggest a higher rate of postoperative atrial fibrillation in the occlusion arm: POAF developed during hospital stay in 47.3% of patients (178 of 376) in the LAAE arm compared with 38.2% of patients (71 of 186) in the no LAAE arm ( P = .047). As a result, postoperative atrial fibrillation is being examined in the LeAAPS trial. Ultimately, it remains to be determined if prophylactic LAAE can reduce stroke risk in patients at increased risk of AF and stroke.
The importance of blinding in LeAAPSWhile randomization is important to ensure balance of baseline characteristics between groups, it does nothing to ensure that there is no differential treatment of the groups over time. The LeAAPS trial has a long follow-up phase that, in an unblinded design, increases the risk of such differential treatment. There is currently a debate whether LAAE can eliminate the need for oral anticoagulation in patients with AF, and some clinicians have a strong bias that it can. Differential use of oral anticoagulation between the 2 arms of the LeAAPS trial would impact the trial. If only a minority of treatment arm patients received oral anticoagulation upon developing AF versus a majority of control arm patients, that would likely attenuate the chances of the trial demonstrating superiority, and is better tested in a noninferiority design. LAAOS III demonstrated benefit of LAAE on top of oral anticoagulation and had balanced use of oral anticoagulation (∼75% at 3-year follow-up) between the arms using the techniques that we have employed in the LeAAPS trial. Therefore, it is essential that, with its superiority design, the LeAAPS trial be blinded and the decision regarding oral anticoagulation use when AF occurs not be influenced by the knowledge of whether the patient received LAAE or not.
ConclusionThe results of the LeAAPS trial will show whether LAAE during routine cardiac surgery reduces stroke or systemic arterial embolism in patients at high risk of AF and stroke undergoing cardiac surgery without pre-existing AF.
CRediT authorship contribution statementRichard P. Whitlock: Writing – original draft, Methodology, Funding acquisition. Patrick M. McCarthy: Writing – review & editing, Methodology. Marc W. Gerdisch: Writing – review & editing, Methodology. Basel Ramlawi: Writing – review & editing, Methodology. John H. Alexander: Writing – review & editing, Methodology. Ibrahim Sultan: Writing – review & editing. David Z. Rose: Writing – review & editing, Methodology. Jeffrey S. Healey: Writing – review & editing, Methodology. Yashasvi Awasthi Sharma: Writing – review & editing, Methodology. Emilie P. Belley-Côté: Writing – review & editing, Methodology. Stuart J. Connolly: Writing – review & editing, Methodology.
Declaration of competing interestDr Whitlock has received institutional research grants from AtriCure, Abbott, Boston Scientific, and Cytosorbents. He has received consulting payments or honoraria from AtriCure, Artivion, Cytosorbents, Edwards Lifesciences, and Bayer. Dr Connolly reports grants from AtriCure, grants and personal fees from Boehringer-Ingelheim, grants and personal fees from Bistol-Myers Squibb, grants and personal fees from Sanofi Aventis, personal fees from Portola, grants from Boston Scientific. Dr Alexander has research grants through Duke University from Artivion/CryoLife, Bayer, Bristol-Myers Squibb, CSL Behring, Ferring, the U.S. FDA, Humacyte, and the U.S. NIH and advisory board or consulting payments from AbbVie, Artivion/CryoLife, AtriCure, Bayer, Bristol-Myers Squibb, Curis, Eli Lilly, Ferring, GlaxoSmithKline, Janssen, Novostia, Pfizer, Portola, Theravance, and Veralox. Dr Rose has received honoraria from AtriCure, Boston Scientific, Cheisi-USA, CSL-Behring, Viz-AI and research support from Medtronic. Dr Ramlawi has received consulting payments from AtriCure, Medtronic, Boston Scientific, Shockwave, and Corcym. Dr McCarthy has received honoraria from AtriCure, Edwards Lifesciences, and a grant from Abbott. Dr Gerdisch has received consulting payments from AtriCure, Artivion, Arthrex, Abbott, Corvivo, and DASI simulations. Dr Healey has received research grants and honoraria from BMS/Pfizer, Medtronic, and Boston Scientific. Dr Belley-Cote has research grants from Bayer, Roche, BMS-Pfizer, and Abbott, and consulting payments from Trimedic Therapeutics Inc. Yashasvi Awasthi Sharma is an employee of AtriCure.
AcknowledgmentsThe LeAAPS trial is sponsored by AtriCure, Inc (Mason, OH, USA). Medical writing support for this manuscript was provided by Latoya M. Mitchell, PhD, CMPP and Alyssa Hahn, PhD of AtriCure, Inc (Mason, OH, USA).
Supplementary materialsSupplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ahj.2024.10.006.
Appendix Supplementary materialsImage, application 1
| Inclusion Criteria | Exclusion Criteria |
| Planned and clinically indicated cardiac surgical procedure requiring opening of the pericardium | Clinically significant atrial fibrillation or atrial flutter anytime in the past
|
| ≥18 years of age | Prior procedure involving opening the pericardium or entering the pericardial space |
| Documentation of any of the following clinical criteria: | Prior LAA occlusion, exclusion, or removal (surgical or percutaneous) |
| | Planned cardiac surgical procedure will be using nonsternotomy approaches ‡ |
| | Patients whose planned procedure is a heart transplant or implantation of any ventricular assist devices |
| | Active endocarditis |
| | Active systemic infection at the time of cardiac surgery requiring antibiotics, including known SARS-CoV2 infections regardless of symptoms |
| | Mental impairment or other psychiatric conditions which may not allow the patient to understand the nature, significance, and scope of the trial |
| Known allergy to nitinol or nickel sensitivity | |
| Known severe symptomatic carotid disease | |
| Known medical condition with expected survival of less than 1 year | |
| Current enrollment in an investigation or trial or an investigational devices or investigational drug that would interfere with this trial | |
| Pregnancy | |
| Other comorbidities that in the investigator's opinion make the patient unsuitable candidate to complete the protocol required visits. |
| Screening/ Baseline | Surgery | Discharge | Month 1 # (30 days + 14 days) | Month 6 # (±30 days) and every 12 months thereafter | Month 12 # (±30 days) and every 12 months thereafter | Final visit | |
| Informed consent | X * | ||||||
| Inclusion/exclusion criteria | X | ||||||
| Demographic information | X | ||||||
| Medical/surgical history | X † | ||||||
| Physical examination | X | ||||||
| Pregnancy test | X ‡ | ||||||
| Blood pressure | X | ||||||
| 12 Lead ECG | X | ||||||
| SAGE | X | X | X | ||||
| EQ-5D-5L | X | X | X | ||||
| Procedure parameters | X | ||||||
| TEE | X § | ||||||
| Medications | X | X | X | X | X | X | |
| AF status ‖ | X | X | X | X | X | ||
| Adverse Events | X | X | X | X | X | X | |
| QVSFS ¶ | X | X | X | X | X |
| Trial | Preoperative AF status | Mean follow-up | Event rate |
| VISION Cardiac
(unpublished, source: PHRI data) | Non-AF | 1 year | 2.8%/yr. |
| Whitlock et al. 44 | Non-AF | 2 years | 2.2%/yr. |
| Horwich et al. 45 | Non-AF | 5.7 years | 2.0%/yr. |
| Biancari et al. 46 | Non-AF | 7.2 years | 1.3%/yr. |
| Butt et al. 47 | Non-AF | 5.1 years | 1.83%/yr. |
| LAAOS III 13 | AF | 3.8 years | 1.84%/yr. |
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