Left Atrial Appendage Occlusion

The field of left atrial appendage occlusion is rapidly evolving. However, several issues remain including the limited randomized efficacy data, peri-device leak, device-related thrombus, and the ongoing refinement of procedural techniques. In this article, we provide a contemporary overview of left atrial appendage occlusion focusing on 4 key remaining challenges: efficacy data, peri-device leak, device-related thrombus, and procedural optimization.

S troke prevention is a centerpiece in the man- agement of atrial fibrillation (AF). 1 Despite their efficacy in preventing ischemic strokes, anticoagulants are not utilized or not maintained in >50% of eligible patients due to bleeding risk, side effects, or noncompliance. 2 Considering the growing size of the AF population and the substantial morbidity and mortality of AF-associated ischemic strokes, left atrial appendage occlusion (LAAO) has emanated as a feasible alternative to address these unmet needs. 3In the last decade, a wealth of data have emerged on the safety of LAAO accompanied with a rapidly growing adoption of the procedure in clinical practice. 4However, several issues remain including the limited randomized data demonstrating LAAO effectiveness and the concerns about devicerelated thrombus (DRT) and peri-device leak (PDL) and their management.In this article, we review the past and present of LAAO and provide a futuristic outlook of this rapidly evolving field focusing on the key remaining open questions (Central Illustration).

LAAO: PAST AND PRESENT
The concept of LAAO dates back to 1949 when John L.
Madden reported the resection of the LAA in 2 patients for the "prophylaxis of recurrent thrombi." 4 Nonetheless, the interest in LAAO remained limited for decades until Blackshear and Odell published their seminal systematic review in 1996 that emphasized the potential role of the LAA as a nidus for thrombus in patients with nonvalvular AF (Figure 1). 5 In the following years, surgical excision of the LAA at the time of concomitant cardiac surgeries became more popular albeit with wide variability in practice and virtually no supportive efficacy data. 6 trials (1,114 patients) with a mean follow-up duration of 2.7 years, the primary efficacy endpoint (composite of stroke, systemic embolism, or cardiovascular or unexplained death) occurred with a similar frequency in both the device and control arms (HR: 0.82; 95% CI: 0.58-1.17;P ¼ 0.27).The rate of ischemic stroke was higher in the device arm (1.6   per 100 patient-years vs 0.95 per 100 patient-years; HR: 1.71; 95% CI: 0.94-3.1;P ¼ 0.08), counterbalanced by a lower rate of hemorrhagic stroke (HR: 0.2; 95% CI: 0.07-0.56;P ¼ 0.002). 7These results remained largely similar in a subsequent patientlevel meta-analysis with 5-year follow-up.Anticoagulation Agents in Atrial Fibrillation)-17 was maintained in a subsequent analysis with 4 years of follow-up. 8,9The main limitation of the trial is that the noninferiority of LAAO was only powered for a composite endpoint that combined ischemic and bleedings events as well as procedural complications.The study was, however, underpowered to assess the impact of LAAO on lowering ischemic events, which is the presumed mechanism of action of the LAAO procedure.
The totality of the data suggests that LAAO is not inferior to anticoagulation in carefully selected patients with nonvalvular AF.However, several concerns remain.1) A key issue with these data is the lack of convincing evidence that supports the mechanism of action of LAAO; reducing cardiac thromboembolism due to exclusion of the LAA cavity from systemic circulation.Indeed, ischemic events were higher in the device arm in PROTECT AF and PREVAIL (Figure 2), raising the question of whether LAAO is effective in eliminating the embolic source or whether its efficacy is merely driven by the mitigation of the bleeding risks associated with long-term anticoagulation.
2) The infrequency of ischemic events in the trial raises some concerns about the fragility of the conclusions.It is likely that the power calculations performed during trial design utilized expected ischemic rates based on historical riskprediction schemes (ie, CHA2DS2-VASc) that are shown to overestimate the risk of ischemic stroke in contemporary practice. 10Hence, the potential need for larger trials to further confirm the role of LAAO for stroke prevention has been raised.Numerous nonrandomized studies have documented the efficacy of LAAO in reducing ischemic stroke and major bleeding. 12However, these studies

HIGHLIGHTS
LAAO has emerged as a promising alternative to oral anticoagulation in selected patients with nonvalvular atrial fibrillation.Although remarkable progress in the field has been made, several questions remain open.
This study summarized the remaining issues with LAAO including the need for more randomized data, device-related thrombus, peri-device leak, and procedural optimization.
Ongoing randomized trials, newer devices, an improved planning software program, and procedural techniques will help address the remaining issues in the field.FDA APPROVAL AND GUIDELINES.The congregate data from PROTECT AF, PREVAIL, and their respective registries led to the approval of LAAO with the Watchman 2.5 (Boston Scientific) device by the Food and Drug Administration (FDA) in 2015.In 2021, a second LAAO device (Amulet, Abbott) was approved by the FDA based on its noninferiority to the Watchman 2.5 device. 13The Amulet investigational device exemption trial, the largest published LAAO trial to date, randomized 1,878 patients to LAAO with the Watchman 2.5 device or the Amulet occluder.The Amulet occluder was noninferior to the Watchman device for the primary effectiveness endpoint (composite of ischemic stroke or systemic embolism at 18 months, 2.8% vs 2.8%; P < 0.001 for noninferiority) and for the composite of stroke, systemic embolism, or cardiovascular/unexplained death (5.6% vs 7.7%; P < 0.001 for noninferiority).Although professional societies eventually incorporated LAAO in their guidelines, their recommendations for LAAO are weak (Class IIb, Level of Evidence: C) and critical of the lack of robust evidence supporting LAAO 14,15 (Table 2).In addition, to ensure the rational dispersion and continuous safety of the procedure, the FDA required LAAO programs to adopt a shared decisionmaking process involving nonimplanting physicians and decision-aid tools and to participate in a national registry for ongoing surveillance of clinical outcomes.

A B B R E V I A T I O
UTILIZATION RATES AND SAFETY DATA.Following FDA approval, the utilization rates of LAAO in the U.S. grew substantially, and the safety profile of the procedure remained excellent.7][18][19][20][21] In addition to providing reassurance regarding the safety of LAAO in commercial settings, a survey of the initial experience with LAAO in the US reveals other important observations: 1. Off-label practices: LAAO for an off-label indication was not uncommon.For example, 14% of patients receiving LAAO in the US had atrial flutter and not AF, a population that was not studied in the RCT. 17In addition, operators frequently used an off-label post-thrombotic regimen.For example, the instructions for use of the Watchman 2.5 device require patients to remain on warfarin for 45 days after the procedure.However, only 51% of patients who received the device in the US between 2016 and 2018 were discharged on warfarin. 22 Disparities in LAAO utilization: Most patients who undergo LAAO in the U.S. were of White race.
In the LAAO registry, Black and Hispanic patients represented only 4.6% and 0.6% of patients, respectively. 17,23 Disparities in LAAO outcomes: Although women have been shown to be at higher risk of major complications after various cardiovascular interventions, the magnitude of difference in outcomes between men and women after LAAO is considerably higher.Data from the LAAO registry and from the national readmission database showed a 2-fold increase in major adverse events with LAAO in women compared with men.24,25 Similarly, Black and Hispanic patients experienced 30% and 90% higher rates of in-hospital complications, respectively, after LAAO than White patients.26 4. Differential impact of device type on safety outcomes: The rate of in-hospital pericardial effusion with the Watchman FLX device was 2.37%, of which w50% were treated with percutaneous drainage, and 11.4% required a cardiac surgery.21 This was substantially reduced with the secondgeneration Watchman FLX device with which the  Other prospective trials that are being currently

DEVICE-RELATED THROMBUS
Thrombus formation on LAAO devices has been a subject of major concern. 30Numerous studies have documented the incidence of DRT, its timing, and its association with adverse events.Fewer studies have investigated the predisposing factors to DRT and the effectiveness of its various management strategies.In a meta-analysis including >10,000 patients, the pooled incidence of DRT was 3.8%. 32In this metaanalysis, the diagnosis was made in <90, 90 to 365, and >365 days in 42%, 57%, and 1% of patients, respectively.In the Amulet IDE trial, the incidence of DRT at 18 months was 3.3% in the Amulet arm and 4.5% in the Watchman arm. 13In a prospective registry with the second-generation Watchman FLX devices, the DRT rate was 1.7% at 1 year with 3 of 7 cases detected beyond 300 days after the procedure. 33INICAL SIGNIFICANCE OF DRT.The association of DRT with thromboembolic events is well established.
In the pivotal Watchman trials, 26.2% of patients with DRT experienced a stroke or systemic embolism event within 6 months of DRT detection. 31In a global dedicated DRT registry, DRT was associated with >3fold increase in the risk of ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00;P ¼ 0.01). 34In the EURO-DRT (European-Canadian device related thrombus registry) registry, the incidence of stroke and death at 2 years among patients with DRT was 13.8% and 20%, respectively. 35In a meta-analysis of 66 studies, the incidence of ischemic stroke was 13.2% in patients with DRT vs 3.8% in patients without DRT (odds ratio: 5.27; 95% CI: 3.66-7.59;P < 0.001). 32SK FACTORS FOR DRT.Identifying predisposing factors for DRT is crucial to optimize risk stratification and procedural outcomes.However, this task has been challenging due to the large number of potential risk factors and the low DRT event rate overall.
Nonetheless, several predictors of DRT have been identified in the literature (Figure 4). 30,34One study attempted to model a risk-prediction scheme (the DRT score) to provide a practical aid for clinicians when considering patients for LAAO.The DRT score was derived from an international registry of 711 patients (237 with and 474 without DRT). 34In this registry, among >40 candidate risk factors considered in the logistic regression model, 5 were independently predictive of DRT (hypercoagulopathy, renal insufficiency, permanent AF, deep device implantation, and pericardial effusion).Although the type of post-LAAO antithrombotic therapy in this global registry did not impact the risk of DRT, other studies yielded opposite conclusions.In the Watchman trials and nested registries, the incidence of DRT was higher when the post-LAAO regimen included antiplatelets therapy alone vs anticoagulation (3.1% vs 1.4%, P ¼ 0.018). 36 the NCDR LAAO (National Cardiovascular Data Registry Left Atrial Appendage Occlusion) registry, a short course of anticoagulation with warfarin or a DOAC after the procedure was associated with a lower incidence of major adverse events through 6 months of follow-up. 22Finally, whether the risk of DRT is device-specific remains uncertain.The Amulet device had a slightly lower DRT rate than the Watchman 2.5 device in the Amulet IDE trial, and this was hypothesized to be related to the larger neo-LAA that remains with plug-based vs disc-lobe device and to the differential impact on device design on healing and endothelialization (Figure 5). 13,37,38This concept remains to be corroborated in further studies.TREATMENT OF DRT.The management of DRT continues to represent a clinical conundrum.Although some studies suggested that oral or parenteral anticoagulants are effective in resolving DRT in majority of patients, several issues remain.First, most patients referred for LAAO are not suitable candidates for intensified or prolonged anticoagulation regimens and may therefore be left with 2 opposing high-risk scenarios (risk of embolic events with DRT vs risk of major bleeding with resumption or initiation of anticoagulation).Second, even among patients treated with anticoagulation, DRT persists in 20% to 25% of them, and they experience substantially higher morbidity and mortality. 34,35Third, even when DRT is resolved with anticoagulation, recurrence rates are high (35% while still on anticoagulation, and 50% when anticoagulation is stopped). 42Finally, not all DRTs are the same, and the management of large and/or highly mobile thrombi remains uncertain.The feasibility of transcatheter aspiration of DRT has been reported, but the safety and efficacy of this approach for the routine management of high-risk DRTs has not been established. 43Iterative LAAO device designing also considered the risk of DRT.For example, the Watchman FLX device has significantly less exposed metal screw on the surface of the device to reduce the risk of DRT.Device manufactures are also exploring novel preventative methods of DRT such as the addition of antithrombotic device coating to minimize the risk of thrombus formation on the device akin to what has been used with drug-coated stents.

PERI-DEVICE LEAK
The proposed mechanism of action of LAAO is that the exclusion of the trabeculated LAA tissue from the systemic circulation will lead to a lower risk of thromboembolic events as the LAA is the source of thrombi in most patients with nonvalvular AF.However, there is ample evidence now that percutaneous LAAO devices frequently do not achieve "complete occlusion" of the appendage, raising the question of whether the term "occlusion" is indeed a misnomer.FREQUENCY OF PDL.The incidence of PDL varies considerably due to the lack of consensus on leak detection and classification methodology.Furthermore, the cutoff for what is considered a potentially significant leak differs across studies.Nonetheless, the literature suggests a high incidence of PDL after LAAO, with higher rates reported in RCTs with core lab adjudication than in observational registries. 44In PROTECT AF, any PDL was present in 40.9% of patients at 45 days, which decreased to 32.1% at 1 year. 45aks >3 mm in diameter were present in 13.3% at 45 days and in 11.8% at 1 year.In the Amulet IDE trial, any PDL at 45 days was present in 37% and 54% of patients randomized to the Amulet vs Watchman device, respectively. 13In addition, leaks >3 mm in diameter were detected in 10% and 25% of patients in the Amulet vs Watchman arms, respectively.In a large real-world study including 51,333 patients enrolled in the NCDR LAAO registry, any PDL was documented in 26.6% of patients at 45 days. 16All the abovementioned studies included patients treated with the first-generation Watchman 2.5 device.The newer Watchman FLX device has not been assessed that the device is effective in achieving a complete seal of the LAA in w94% of patients. 46INICAL IMPACT OF PDL.Studies attempting to assess whether PDL is associated with a negative impact on clinical outcomes were challenged by several important limitations.First, the rate of stroke or systemic embolization following LAAO is low, and hence, exploring the independent impact of PDL on outcomes requires a very large sample size.Second, the definition of significant vs insignificant leak varies between sites, relies mostly on arbitrary cutoffs of the leak diameter (eg, >3 mm, >5 mm), and does not consider the various mechanisms of the PDL (Figure 7). 47,48Third, there is a wide variability in the assessment and classification of PDL in clinical practice.Fourth, patients with large leaks are currently recommended to remain on anticoagulation, and hence, assessing the differential impact of the residual leak on outcomes in these patients is confounded by a major treatment bias.Therefore, until recently, all published studies that explored this question concluded that PDLs were not associated with thromboembolic events. 33,45,49,50Nonetheless, 2 recently presented studies have challenged this assumption.The first is an analysis from the NCDR  LAAO registry that documented an association between small leaks (defined as those <5 mm) detected at 45 days after LAAO and major adverse events (driven by ischemic stroke and transient ischemic attack) through 1 year (HR: 1.15; 95% CI: 1.02-1.29). 16e second is a long-term analysis from PROTECT-AF and PREVAIL trials and the continuous access to PROTECT AF-2 prospective registry. 51In this analysis, small leaks (<5 mm) detected at 1 year were significantly associated with stroke/systemic embolization (9.9% vs 5.1%, P ¼ 0.008) (Figure 8).
MANAGEMENT OF PDL.The recent data on PDL suggested that the commonly encountered PDL may not be benign and carries a hazard of major adverse events.However, these studies offered no further insights into the ideal management strategies of PDLs.The current literature of PDL management is sparse.Techniques to minimize PDLs have been described, but data on their impact on PDL mitigation are limited.3][54] Although these studies showed that complete or near-complete obliteration of the leak is feasible in >90% of patients with low complication rates, the long-term efficacy of this approach is unknown. 49Watchful waiting has been proposed as a potential strategy for patients with smaller PDLs due to the documented regression of leaks <5 mm in 20% to 40% of patients. 33,45,55ether this is a true leak regression due to atrial remodeling or whether it represents variations in imaging acquisition and interpretation is uncertain.It might be reasonable to observe these patients with repeated imaging considering the limited safety and efficacy data on the alternative approaches such as resumption of anticoagulation or interventional leak closure.

PROCEDURAL OPTIMIZATION
Data from the NCDR LAAO registry documented excellent procedural outcomes with early commercial experience with LAAO in the U.S., including an implantation success of >98% and major complication rate of 2.2%. 17Yet, opportunities for further improvement remain considering the preventative nature of the procedure.
PROCEDURAL VOLUMES.Contrary to other structural heart interventions, there are no specific institutional requirements to starting an LAAO program besides having surgical backup on site. 56Hence, the number of hospitals and physicians performing LAAO exceeded 490 and 1,100, respectively, within 2 years after the FDA approved the procedure. 21During the same period, the median annual institutional and Nazir et al 57 showed that a low procedural volume (<15 per year) was associated with a 2-fold increase in major adverse events.Jung et al 19 suggested a threshold of 32 cases per institution are needed to attain procedural proficiency.Most recently, data from the Amulet IDE trial revealed that the higher rate of pericardial effusion in the Amulet device arm was driven by the inexperience of U.S. operators with the device, suggesting that the impact of operator's experience on safety outcomes may be device-specific. 58With the rapid growth in the number of hospitals and operators performing LAAO and the number of available LAAO devices, there is a need to define the appropriate general and device-specific LAAO experience at both the hospital and the individual operator level to ensure the continuous safety and efficacy of the procedure.Furthermore, there is a need to collate site-specific performance metrics beyond procedural complications (eg, quality of shared decision-making and the adequacy of LAA closure) to better evaluate LAAO programs.
PROCEDURAL PLANNING.TEE is considered the gold-standard modality to assess the size and shape of the LAA prior to the procedure.3][64] Nonetheless, a contemporary software program not only provides a user-friendly platform to assess the LAA sizing but also allows virtual implantation of various devices to assess the location, seal, and compression with different LAAO approaches (Figure 9).This has been shown to improve device selection, reduce the number of implantation attempts, and improve procedural time. 65Furthermore, recent studies have shown that CCT is more sensitive than TEE in the detection of postprocedural device    .This approach has also been shown to reduce the cost of the LAAO procedure by 15%. 77Recent data from a large sample of academic centers in the US revealed a rapid uptake in same-day discharge in the last 2 years with rates approaching 25% of all cases in 2021 (Figure 11).
C o n t r a s t -l e s s L A A O .Patients referred for LAAO are usually elderly and have a high (15%-25%) prevalence of chronic renal insufficiency. 17,78-80Hence, these patients are at risk of developing acute kidney injury (AKI) after the procedure, which has been shown to carry major negative prognostic implications.In 1 study, the incidence of AKI after LAAO was 9%, and this was associated with a 2.5-fold increase in allcause mortality at 18 months. 80In another study, AKI after LAAO was associated with a 60% higher readmission rate at 6 months. 79Hence, efforts have been made to optimize iodine contrast usage in the procedure to mitigate the risk of AKI.Proof-ofconcept studies have shown the utility of contrastfree LAAO aided by 3D TEE, ICE, or 3D ultrasound mapping (Figure 12). 81,82If validated in future studies, contrast-free LAAO can be a promising alternative for

11 3 )
These trials only enrolled patients who are deemed candidate for a short-term course of anticoagulation after the procedure.No randomized data are yet available to support LAAO in patients with absolute contraindication to anticoagulation.The only RCT that was designed to assess this population (ASAP-TOO [Assessment of the WATCHMANÔ Device in Patients Unsuitable for Oral Anticoagulation] trial; NCT029284 97) was terminated due to enrollment difficulties although follow-up for the enrolled patients will continue through 5 years.

FIGURE 1
FIGURE 1 The Left Atrial Appendage as a Nidus for Thrombus Formation in Patients With Atrial Fibrillation

FIGURE 2 2
FIGURE 2 Patient-Level Meta-analysis Illustrating 5-Year Pooled Outcomes of PROTECT AF and PREVAIL Trials rate of pericardial effusion requiring intervention was only 0.42%.27    5. Current data in the U.S. pertain only to the Watchman FLX device and its predecessor; Watchman 2.5.Postmarket outcome data with the recently approved Amulet device in the U.S. are not yet available.EFFICACY DATA FOR LAAO PROTECT AF and PREVAIL paved the way for regulatory approval of LAAO in the U.S. in 2015.However, societal guidelines on AF management highlight the need for more randomized data supporting the efficacy of LAAO. 14,15Several prospective trials have been commenced to address this need.A summary of the trials, their objective, and their characteristics is shown in Tabel 3. The results of these trials will be essential to further validate the efficacy of the LAAO concept overall and to assess its role in low-risk patients as well as in special population (eg, patients with contraindication to anticoagulation, patients with aortic stenosis undergoing transcatheter aortic valve replacement, and patients undergoing catheter ablation for AF).

FIGURE 3
FIGURE 3 Procedural Outcomes in the NCDR LAAO Registry

J 2 6
A C C : A D V A N C E S , V O L . 1 , N O . 5 , 2 0 2 Alkhouli et al D E C E M B E R 2 0 2 2 : 1 0 0 1 3 Advances and Open Questions with LAAO FREQUENCY AND TIMING OF DRT.The incidence of DRT in PROTECT AF, PREVAIL, and their nested continuous access registries was 3.74%. 31Notably, one-third of DRT cases were detected at the time of unplanned transesophageal echocardiograms (TEEs).
Emerging concepts in DRT prediction include the potential role of flow dynamics on thrombus formation and the early detection of DRT precursors using cardiac computed tomography (CCT).Mill et al 39 reported a proof-of-concept use of computational modeling to potentially predict DRT based on flow dynamic patterns.Using a web-based interactive virtual implantation platform, Aguado et al 40 showed that computational flow dynamic simulations may be able to predict the most appropriate LAAO configurations (type of device, size, landing zone) for a given patient-specific LAA morphology to reduce the risk of DRT.A multicenter collaborative study is currently underway to further explore this concept with preliminary data showing promising results.The growing use of CCT in post-LAAO surveillance also afforded a unique opportunity to further understand the patterns of DRT on contemporary LAAO devices.In a recent study by Kramer et al, 41 the authors assessed the frequency and phenotypes of hypoattenuated thickening (HAT) observed on CCT after LAAO with the Watchman FLX device.Although the

FIGURE 4 2
FIGURE 4 Predictors of DRT in the LAAO Literature

FIGURE 6 2
FIGURE 6 Suggested Algorithm for Assessment of Device Thrombus and Hypoattenuating Thickening After LAAO With the Watchman FLX Device

FIGURE 7
FIGURE 7 Mechanism of Peri-Device Leak After Left Atrial Appendage Occlusion With the Watchman Device

J
A C C : A D V A N C E S , V O L . 1 , N O . 5 , 2 0 2 2 oughly studied.Only 1 study to date suggested a potential positive impact of routine preprocedural CCT on reducing the risk of PDL after LAAO.The emergence of various occluder devices with enhanced sealing mechanisms and the availability of steerable delivery sheaths may further enhance the operator's ability to attain complete closure of the LAAO although studies supporting this assumption remain necessary.

FIGURE 8
FIGURE 8 Clinical Impact of Peri-Device Leak After Left Atrial Appendage Occlusion With the Watchman Device

FIGURE 9
FIGURE 9 Computational Modeling for Optimization of Left Atrial Appendage Occluder Implantation

J
A C C : A D V A N C E S , V O L . 1 , N O . 5 , 2 0 2 2 complications such as DRT or PDL. 62,66Albeit speculative, CCT may soon become the imaging tool of choice for pre-and post-LAAO assessments with easyto-use machine learning-enabled interactive platforms that can be embedded in the routine workflow of the LAAO practice. 67-69THE MINIMALIST APPROACH.Akin to what has been observed with transcatheter aortic valve replacement, there is a growing adoption of a minimalist approach to LAAO.This has manifested with the rising interest of intracardiac-echo (ICE)-guided LAAO, the emergence of contrast-free LAAO, and the increasing trends for same-day discharge following the procedure.I C E -g u i d e d L A A O .The feasibility for ICE (vs TEE)guided LAAO has been confirmed in many singlecenter and multicenter observational studies. 70Yet, the adoption rate of ICE in U.S. LAAO practices remained low primarily due to the associated learning curve, the limitations of 2D-ICE, the limited offering of formal educational programs, and the few consensuses regarding the optimal methodologies for imaging acquisition, interpretation, and reporting. 71Efforts to validate simple and effective ICE imaging techniques are underway (Figure 10).In addition, the advent of novel 3D-and 4D-ICE technologies has transformed intraprocedural imaging, refueling the interest in ICE-guided LAAO especially during the

FIGURE 10
FIGURE 10 Simplified Imaging Protocol for ICE-Guided LAAO

FIGURE 11
FIGURE 11 Trends in Same-Day Discharge After Left Atrial Appendage Occlusion

TABLE 1
Key Findings of the LAAO Randomized Clinical Trials CrI ¼ credible interval; CV ¼ cardiovascular; DOAC ¼ direct oral anticoagulant; LAAO ¼ left atrial appendage occlusion; PREVAIL ¼ Evaluation of the WATCHMAN Left Atrial Appendage (LAA) Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy); PRAGUE ¼ Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation; PROTECT AF ¼ WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation; RR ¼ rate ratio; SE ¼ systemic embolization; sHR ¼ subdistribution hazard ratio; TIA ¼ transient ischemic attack.

TABLE 2
Current U.S. and European Guidelines on the Use of Percutaneous LAAO Devices ACC ¼ American college of cardiology; AF ¼ atrial fibrillation; AHA ¼ American heart association; COR ¼ class of recommendation; EACTS ¼ European Association for Cardio-Thoracic Surgery; ESC ¼ European Society of Cardiology; FDA ¼ Food and Drug Administration; HRS ¼ Heart Rhythm Society; LAA ¼ left atrial appendage; LOE ¼ level of evidence.
R E F E R E N C E S