Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia and the cause of thromboembolic events in elderly patients worldwide. AF is associated with a significantly increased risk of morbidity and mortality due to cardiac emboli, primarily from left atrial appendage (LAA) thrombus. Oral anticoagulation therapy is the standard treatment to effectively reduce the risk of thromboembolic events in patients with AF. However, anticoagulation treatment increases bleeding risk. LAA closure (LAAC) has recently been introduced as a feasible mechanical preventive intervention for thromboembolic events while minimizing the risk of bleeding. Transcatheter LAAC devices have evolved in the past decade, and several ongoing trials have demonstrated the improvements of safety and outcomes in newer generation devices. This review summarizes the current perspectives and outcomes regarding LAAC as an alternative to pharmacologic therapy.
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Avoid common mistakes on your manuscript.
Atrial fibrillation (AF) is the most common cardiac arrhythmia and associated with high risk of thromboembolism. |
Left atrial appendage (LAA) is a main source of thrombus associated with AF. |
Oral anticoagulation therapy is the standard treatment for reducing the risk of thromboembolic events in patients with AF. |
Anticoagulation treatment increases bleeding risk. |
Left atrial appendage closure (LAAC) is a feasible alternative to pharmacologic intervention for preventing thromboembolic events and minimizing bleeding risk. |
Introduction
The prevalence of atrial fibrillation (AF) is high in clinical practice and significantly increases the risk of death related to ischemic embolic stroke and peripheral embolism. In fact, patients with AF have a fivefold higher stroke rate than those without AF [1]. The left atrial appendage (LAA) is widely acknowledged as the primary site of thrombus formation. This assertion is substantiated by numerous previous studies consistently demonstrating a robust link between thrombus formation within the LAA and AF [2, 3]. The CHADS2 and CHA2DS2-VASc scores are commonly used methods to predict and estimate the risk of stroke in patients with AF (Table 1) [4, 5]. In contrast, the HAS-BLED score is used to calculate the major bleeding risk, defined as intracranial bleeding, bleeding requiring hospitalization, decrease of ≥ 2 g/dL in hemoglobin level, or the need for transfusion secondary to bleeding (Table 1) [6]. Both risk scores have been incorporated into clinical guidelines for determining anticoagulation, but it is important to note that many common risk factors were included in both scores. In summary, thromboembolic and bleeding risks are closely related, and treatment strategy should be considered with this in mind. Recently, left atrial appendage closure (LAAC) has emerged as an alternative treatment for patients with AF at high risk of stroke. Although clinical outcome data for LAAC is currently limited, ongoing trials are expected to offer more insights, and newer LAAC devices may prove beneficial.
This article aims to review the current clinical evidence regarding LAAC in comparison to anticoagulation therapy for patients with AF. Additionally, we will discuss the management before and after LAAC implantation, as well as newer devices that hold promise for improved outcomes in the future, supported by clinical data.
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
Literature Search
A designated reviewer meticulously analyzed abstracts and procured full-text versions for those aligning with our eligibility criteria with publication dates up to 13 July 2023. Additionally, we reviewed reference lists to identify pertinent studies that may have eluded the primary search. Our search strategy utilized various keyword combinations, such as “atrial fibrillation”, “left atrial appendage closure”, “LAAC”, and “Watchman.”
Study Selection
Inclusion criteria included available full-text version; randomized controlled trials, prospective or retrospective in nature; involve patients with nonvalvular AF who underwent LAAC; and present comparative data on LAAC versus anticoagulation therapy. Exclusion criteria encompassed animal studies; conference abstracts; case reports; and any research not providing primary outcomes such as all-cause mortality, strokes, among others, or containing insufficient data to evaluate both efficacy and safety.
Preprocedural Evaluation of LAAC
As mentioned above, the LAA is a major site of thrombus formation. The anatomy of the LAA is unique and has wide variability in size and shape. Ernst et al. demonstrated that volume, length, width, and orifice diameter of the LAA ranged from 0.7 to 19.2 cc, 16–51 mm, 10–40 mm, and 5–27 mm, respectively [7]. Veinot et al. also reported that 54% of LAAs had two lobes; the number of lobes can be anywhere between one and four [8]. Because the anatomical variety of the LAA requires a tailored procedural strategy, it is essential to conduct a preprocedural imaging evaluation of the complexity and variability of LAA morphology, particularly for the percutaneous LAAC procedure.
TEE
Transesophageal echocardiography (TEE) is used extensively for ultrasonographic examination of the LAA because the proximity of the esophagus to the LAAs allows TEE to provide higher-quality images than transthoracic echocardiography (TTE). TEE is performed to clinically evaluate LAA anatomy and the presence of thrombus in the LAA. Additionally, TEE, together with fluoroscopy, is essential to determine the size and position of LAAC devices during the procedure and to evaluate residual leak following the intervention. Although TEE is a valuable aid during the LAAC procedure, it should be noted that intraoperative TEE measurements do not always match preoperative measurements, likely because of dynamic LAA volume change that is dependent on the left atrial pressure.
CT
Computed tomography (CT) is a valuable imaging modality for visualizing the anatomy of the LAA. Several types of LAA morphology, such as “wild socks,” “chicken wings,” “cauliflowers,” and “cactus,” can be better characterized. The chicken wing morphology is the most common shape, and the cauliflower type is most often associated with thromboembolic events [9]. CT images can be used to confirm the anatomy of the LAA and determine patient eligibility for LAAC. CT is also useful for periprocedural planning and postprocedural evaluation.
CMR
Cardiac magnetic resonance imaging (CMR) can be a good alternative to CT for the strategic planning of LAAC procedures in patients with chronic kidney disease to avoid contrast-induced renal injury. Additionally, sedation or radiation exposure is not required for CMR. CMR provides accurate measurements and evaluates myocardial fibrosis, structural remodeling, and thrombus formation in the LAA. Dallan et al. demonstrated the technical feasibility of CMR for LAAC [10]. A total of 10 patients who underwent CMR preprocedural planning for LAAC were enrolled in the study. All patients underwent successful implantation, with no complications in this series. Its high cost and unavailability in some centers are major limitations hindering its use as a standardized preprocedural imaging tool for the procedural strategy of LAAC.
Anticoagulation Therapy
Anticoagulation therapy has been a standard and effective strategy in reducing the incidence of thromboembolic events in patients with paroxysmal and chronic AF. For decades, anticoagulation with vitamin K antagonists (VKAs) has been the standard care for the prevention of thromboembolic events in patients with AF, since warfarin is proven to be more effective than aspirin and dual antiplatelet therapy in reducing cerebral events [11,12,13]. However, the bleeding risk in patients receiving VKA therapy is higher than in patients receiving aspirin [14]. Non-VKA oral anticoagulant (NOAC) is a newly established alternative anticoagulation therapy with a lower bleeding risk than that of VKA. Further, several studies have demonstrated that NOAC is more effective and safer than VKA [15] for stroke prevention in nonvalvular AF (NVAF).
Mechanical Preventive Treatment
Bleeding complications and non-adherence remain a concern, especially in elderly patients who may be at even higher risk of thromboembolic events associated with AF. In fact, as a result of concern for high bleeding risk, approximately 40–50% of patients do not receive anticoagulation despite of its proven benefit to prevent thromboembolic events [16, 17]. Therefore, mechanical preventive interventions, including the surgical exclusion of the LAA and percutaneous LAAC, have been introduced in clinical practice as a potential valuable alternative to medical management in preventing thromboembolic events in patients with AF. Most LAAC trials do not explicitly include patients with AF who have experienced major bleeding events after receiving NOAC. Consequently, the existing guidelines, primarily derived from clinical trials, assign a Class IIb recommendation for both surgical LAA resection and percutaneous LAAC procedures in patients with contraindications to anticoagulation (Fig. 1).
Recommendation for percutaneous and surgical LAA occlusion. ACC American College of Cardiology, AHA American Heart Association, ESC European Society of Cardiology, HRS Heart Rhythm Society, LAA left atrial appendage, OAC oral anticoagulation. COR-IIb is defined as usefulness/efficacy is less established by evidence/opinion (European guidelines), benefit ≥ risk (American guidelines)
Surgical LAAC
Surgical exclusion of the LAA has been used in patients undergoing concomitant procedures, such as coronary revascularization or valve repair. The left atrial appendage occlusion (LAAOS) study was the first randomized study on surgical LAA exclusion. The results of the LAAOS study demonstrated the safety of surgical LAA exclusion during coronary artery bypass surgery [18]. However, complete closure of the LAA was observed in only 45% (5/11) of the cases using sutures and in 72% (24/33) of cases using a stapler. Other studies have also shown that incomplete closure is associated with thromboembolic events [19]. Novel surgical techniques for surgical LAAC have been introduced over time [20,21,22,23]. The AtriClip (Atricure, Dayton, Ohio, US) is a useful device for the management of epicardial LAA, contributing not only to complete exclusion of the LAA but also its electrical isolation [24]. A recent multicenter randomized trial has shown that concomitant surgical LAAC performed during the surgery was associated with a lower risk of ischemic stroke or systemic embolism [25]. Although the trial demonstrated surgical LAAC as a concomitant procedure provided excellent outcome, there is still insufficient evidence for isolated surgical LAAC in patients with AF.
LAAC Device
In recent years, several LAAC devices have been developed and introduced as alternatives to anticoagulants for stroke prevention. The Percutaneous Left Atrial Appendage Transcatheter Occlusion (PLAATO) device (eV3, Inc., Plymouth, MA, USA) was the first percutaneous device to be implanted in humans [26]. The device consisted of a self-expandable nitinol frame coated with non-thrombogenic polytetrafluoroethylene, with anchors along three posts to secure the device to the LAA. Previous trials have shown that LAAC with the PLAATO device is safe and effective in patients with NVAF [27, 28]. However, the PLAATO device is no longer commercially available.
The Watchman device (Boston Scientific, Natick, Massachusetts) is a dedicated LAAC device, secondary to the PLAATO device, which received US Food and Drug Administration (FDA) approval after the pilot study [29] in March 2015. The Watchman device is parachute-shaped and self-expanding with a nitinol frame. The device is covered by a membrane cap made of polyethylene terephthalate fabric facing the left atrium body. This membrane prevents thrombus embolization from the LAA and promotes endothelialization. The device is available in five sizes, ranging from 21 to 33 mm, and is the most studied LAAC device. We summarized the previous studies comparing the clinical outcomes of LAAC to oral anticoagulation (OAC) in Table 2. PROTECT-AF trial was a multicenter randomized controlled trial conducted in the USA and Europe between 2005 and 2012. The 707 eligible patients with NVAF and CHADS2 scores of ≥ 1 were randomly assigned in a 2:1 ratio to either LAAC using the Watchman device or warfarin. Warfarin was continued for 45 days after device implantation. Clopidogrel treatment followed for 6 months, and aspirin was administered indefinitely. This trial revealed that LAAC was noninferior to warfarin therapy alone in preventing cardiovascular death, stroke, or systemic embolism in patients with NVAF [30]. PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients with Atrial Fibrillation Versus Long-Term Warfarin Therapy) was another major prospective randomized trial [31] that enrolled 407 patients with AF and CHADS2 scores of ≥ 2 and randomly assigned them to either Watchman LAA closure or warfarin groups in a 2:1 ratio, using a similar primary endpoint to that of PROTECT-AF. In this trial, LAA occlusion was noninferior to warfarin for ischemic stroke prevention or systemic embolism at more than 7 days post procedure. Although noninferiority was not achieved for overall efficacy, event rates were low, and procedural safety significantly improved, compared with PROTECT-AF. A 5-year combined patient-level meta-analysis of PROTECT AF and PREVAIL has demonstrated that LAAC with Watchman is effective in preventing stroke in NVAF, offering comparable results to warfarin. Furthermore, LAAC with Watchman presents additional advantages, including reductions in major bleeding events, particularly hemorrhagic strokes, and decreased mortality rates [32]. In the recent era, NOACs have gained popularity due to their efficacy, which is similar or superior to VKAs in NVAF management, along with a lower rate of intracerebral bleeding [33, 34]. The Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation (PRAGUE-17) trial, a multicenter randomized noninferiority trial comparing LAAC with NOACs, has provided valuable insights. PRAGUE-17 demonstrated that LAAC is noninferior to NOACs in preventing major AF-related cardiovascular, neurological, and bleeding events among high-risk patients for stroke with an increased risk of bleeding [35]. While PRAGUE-17 has started to explore the potential of transcatheter LAAO as an alternative for NOAC candidates, it is worth noting that the enrolled patients in this trial were already at a high risk for bleeding or had failed oral anticoagulant treatment. Moreover, efficacy and safety endpoints in this noninferiority design were combined in the study. Currently, several complication randomized trials with larger sample sizes and longer follow-up periods aim to provide more comprehensive data (Fig. 2). These trials intend to demonstrate individual ischemic and bleeding endpoints in patients who are optimal candidates for NOAC therapy. Larger sample sizes will enable more robust analyses and investigations into specific subgroups within the population.
The CAP Registry was another study conducted on 566 patients that suggested that Watchman implantation is a favorable and safe alternative and that complications associated with Watchman implantation significantly decrease in frequency with operator experience [36]. In 2015, a meta-analysis of 2406 patients with NVAF reported that patients who underwent LAAC had significantly fewer hemorrhagic strokes (hazard ratio [HR] 0.22, p = 0.004), cardiovascular and all-cause deaths (HR 0.48, p = 0.006), and bleeding (HR 0.51, p = 0.006) than those who received warfarin, with a mean follow-up of 2.69 years [37]. The Initial US clinical experience has evaluated the procedural outcomes and complication rates of all patients with the Watchman device in the USA since FDA approval [38]. Among 3822 consecutive patients, the device was successfully implanted in 3653 (95.6%) patients, with a median procedure time of 50 min (range 10–210 min). Procedural complication rates included 39 pericardial tamponades (1.02%), 3 procedure-related strokes (0.078%), 9 device embolizations (0.24%), and 3 procedure-related deaths (0.078%). Additionally, 71% of implanting physicians performed these procedures for the first time. Nevertheless, the study showed a high clinical success rate for the procedures and a low complication rate. The clinical outcomes of the Watchman device for LAAC are summarized in Table 3. Watchman FLX (Boston Scientific) is a newer generation of LAAC devices that has been available since November 2015. The Watchman FLX devices are available in five sizes (20–35 mm) for ostia measuring 15–32 mm wide. The variety of device sizes allowed for the treatment of both smaller and larger LAA ostia, compared with the Watchman device. Additionally, a shorter Watchman FLX device enables implantation even in chicken-wing-shaped LAAs with shallow or broad LAAs. There are some key differences between the previous generation of Watchman and the Watchman FLX, such as the polyester fabric coverage, distal end design, number of anchors and struts, proximal face, and recommended compression. A fully rounded ball design is beneficial for safely advancing and maneuvering within the LAA. Partial and full device recaptures were performed during the procedure, if necessary, to achieve precise placement in the LAA. Some studies showed the high procedural success rate of LAAC with Watchman FLX and favorable outcomes [39,40,41]. Additionally, the SURPASS study of the National Cardiovascular Data Registry Left Atrial Appendage Occlusion (NCDR-LAAO) Registry was real-world data including the largest number of patients who underwent Watchman FLX. The results showed that safety and efficacy was similar to those of a previous study [42].
Indication for LAAC
In a previous study using data from the NCDR LAAO Registry, the most frequently reported procedural indications at clinical sites were an elevated risk of thromboembolic stroke and a history of major bleeding [43]. Consequently, concerns related to a high risk of falls and patient preference were raised. A noteworthy finding from this analysis was that a significant majority of patients had documented histories of clinically significant bleeding, predominantly stemming from gastrointestinal sources, with intracranial bleeding reported in approximately 12% of the cohort. In parallel, the European Heart Rhythm Association Survey identified the most frequent applications of LAAO in patients with a CHA2DS2-VASC score ≥ 2 with a contraindication to OAC, a CHA2DS2-VASC score ≥ 2 combined with a HAS-BLED score ≥ 3, occurrences of embolic events despite OAC administration, and a CHA2DS2-VASC score ≥ 2 in the presence of end-stage renal failure [44]. Consequently, these findings highlighted a high risk for stroke and bleeding as primary indications for LAAO. Contrastingly, 13.3% of patients enrolled in the PROTECT-AF and PREVAIL randomized clinical trials had experienced prior bleeding events [30, 31]. The observed disparities in patient characteristics may stem from variations in the inclusion criteria of pivotal trials, which guided FDA approval of the device, and actual clinical practice. While pivotal trials enrolled patients boasting a CHA2DS2-VASC score ≥ 1, making them eligible for long-term OAC, real-world scenarios led to the consideration of short-term OAC therapy for patients with a CHA2DS2-VASC score ≥ 3, as they were deemed unsuitable for long-term OAC therapy. We summarized the indications and contraindications for LAAC procedure in Table 4.
Antithrombotic Strategy After LAAC
Postimplantation anticoagulation and antiplatelet therapy management remain clinical concerns because most patients who undergo LAAC have a high risk of bleeding. In previous trials, warfarin and aspirin were administered 45 days after LAAC device implantation. If device-related thrombosis (DRT) was not detected on TEE at 45 days, warfarin was discontinued. Aspirin and clopidogrel were then administered for 6 months, followed by aspirin indefinitely. This is a standard and recommended regimen following LAAC device implantation. Current guidelines recommend oral anticoagulants for 45 days, followed by dual antiplatelet therapy (DAPT) for 6 months for DRT and potential stroke events [45]. However, controversy surrounds the use of antithrombotic therapy in patients with LAA occlusion. The ASA Plavix Feasibility Study with Watchman Left Atrial Appendage Closure Technology (ASAP) was conducted in patients with both high bleeding risks and absolute contraindications to warfarin [46]. This multicenter prospective nonrandomized study assessed the safety and efficacy of LAAC with the Watchman device in patients with NVAF and CHADS2 scores of ≥ 1 who were ineligible for OAC. DAPT was administered for 6 months after LAAC without warfarin. There were four cases of all-cause mortality or systemic embolism (2.3% per year), three cases of ischemic stroke (1.7% per year), and one case of hemorrhagic stroke (0.6% per year). The authors concluded that using the Watchman device with DAPT, instead of warfarin transition, as a postprocedure OAC is a reasonable option for patients at high risk for stroke with contraindications to systemic OAC. However, previous study reported that DAPT after LAAC is associated with a substantial incidence of bleeding events. The use of low-dose NOACs may provide an ideal balance between keeping the risk of thromboembolic events low and reducing the likelihood of bleeding events in patients with NVAF after LAAC. The ELDERCARE-AF (Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients) trial demonstrated a reduction in stroke or systemic embolism with once-daily 15 mg edoxaban in Japanese patients with AF aged 80 years or older ineligible for standard OACs [47]. Moreover, Della Rocca et al. reported that long-term half-dose NOAC significantly lowered the risk of the composite endpoint, including DRT, thromboembolic events, and major bleeding events, compared to a standard antithrombotic therapy based on antiplatelets [48]. We summarized antithrombotic treatment after LAAC in both previous and ongoing trials in Table 5. It should be noted that the evidence supporting reduced-dose anticoagulant regimens after LAAC is currently limited. Thus, further investigation in antithrombotic therapy for LAAC is required to determine the optimal regimen for patients with AF.
Complications
Some data and evidence are available regarding the safety and efficacy of LAAC devices that have been developed over time. However, LAAC is not devoid of complications. LAAC is a prophylactic treatment and avoiding complications of the procedure is imperative. PROTECT-AF reported a relatively high rate of complications including cardiac tamponade (4.3%), procedure-related stroke (1.15%), and device embolization (0.6%) [30]. A meta-analysis that included 49 studies involving 12,415 patients showed that the pooled proportion of all-cause stroke was 0.31%, major bleeding requiring transfusion was 1.71%, and pericardial effusion was 3.25% [49].
Pericardial effusion is a common and serious complication of LAAC. Catheter and device manipulations within the thin-walled LAA cause pericardial effusion, especially in transseptal punctures. The anchors and outward radial force of the device can damage the LAA wall. Observational modalities, such as TEE, during the procedure, are essential to prevent pericardial effusion. If complications arise, percutaneous or surgical drainage may be considered to stabilize the hemodynamics. Air embolization is a rare but potentially fatal complication, and the use of large delivery sheaths for LAAC is a risk factor for air embolization. Periprocedural stroke due to thrombus and debris is also a rare but devastating complication.
Device embolization is an acknowledged complication of LAAC procedures, with an incidence rate of less than 2% reported in clinical practice [50]. Device embolization occurred more frequently postoperatively, requiring surgical retrieval, and had higher mortality rates than intraoperative embolization. Size mismatch and inexperienced operators may be the main reasons for device embolization [51].
Peridevice leaks remain a risk factor for stroke risk, due to the inherent anatomical complexity of the LAA, which presents a challenge to achieving complete conformity with the LAAC device and the LAA orifice. The Watchman FLX device offers advantages by enabling distal positioning during deployment, as well as the ability to recapture and redeploy the device, which proves beneficial in preventing postimplantation leaks. Nevertheless, it is important to highlight that in the PINNACLE FLX study, leaks measuring less than 5 mm occurred in 10.5% of patients at 1 year after LAAC with Watchman FLX devices [39]. Dukkipati et al. reported that leaks of less than 5 mm following percutaneous LAA closure with the Watchman device were associated with an increased risk of ischemic stroke or systemic embolism [52]. Hence, it is crucial for operators to carefully optimize device positioning to minimize peridevice leaks during implantation, with the assistance of TTE.
DRT after device implantation remains a major concern and is typically detected during routine follow-up after LAAC or after an ischemic event using TTE or CT. Recent studies have reported that DRT after LAAC is strongly associated with a higher risk of thromboembolic events, with an incidence ranging from 1.6% to 16% [53, 54]. The causative risk factors for DRT include patient characteristics, procedural factors, device specifications, and post-LAAC medical regimens. Although continued anticoagulation therapy is effective in resolving this problem and preventing DRT recurrence [55], long-term anticoagulation increases bleeding events in populations with high bleeding risk. Optimal diagnostic criteria and treatment regimens for DRT are warranted in the future.
Other New Devices
Amplatzer Amulet Left Atrial Appendage Occluder
The Amplatzer Cardiac Plug (ACP) (St. Jude Medical, Minneapolis, MN, USA) is one of the most commonly used devices for percutaneous LAAC and received Conformité Européenne (CE) mark approval in 2008. The ACP is constructed from a mesh of woven nitinol, with the lobe and disk connected by a flexible waist. The lobe is held in the neck of the LAA and stabilized by retention wires, and the disc seals the orifice of the LAA. The Amplatzer Amulet system (Abbott Vascular, Santa Clara, CA, USA) is a second-generation LAAC device commercially available in Europe since 2013. The Amulet device has a larger disc diameter, a longer lobe and waist, and more retaining wires than the ACP device. The Amulet device is preloaded within the delivery system and available in eight different sizes (16–34 mm). The larger size of this device allows for the treatment of a wider range of anatomical variations. A multicenter prospective real-world registry with the second-generation Amulet device included 1088 patients (aged 75 ± 8.5 years, 64.5% male; CHA2DS2-VASc, 4.2 ± 1.6; HAS-BLED, 3.3 ± 1.1) with NVAF who showed high implant success rates (99%) and lower periprocedural complication rates (3.2%), compared with those of first-generation ACP registries [56]. Moreover, the Amulet IDE trial (Amplatzer Amulet Left Atrial Appendage Occluder IDE Trial) was conducted to assess the safety and efficacy of the Amulet device compared with the Watchman device [57]. The Amulet IDE trial was a large randomized, multicenter, controlled trial conducted on 1878 patients with high risks of stroke or systemic embolism. The Amulet group had a slightly higher success rate in the initial implantation procedure (98.4% vs. 96.4%). The Amulet device achieved comparable results to the Watchman device on the primary effectiveness endpoint (2.8% vs. 2.8%, p < 0.001 for noninferiority) and the composite of stroke, systemic embolism, and all-cause death (5.6% vs. 7.7%, p < 0.001 for noninferiority). Recently, a finding of the extended follow-up in the Amulet IDE trial was presented which showed that the Amulet device provided similar clinical outcomes to those of the Watchman device over 3 years.
WaveCrest
The Wavecrest LAA device (Biosense Webster, Inc., Irvine, CA) received CE Mark approval in 2013 but is not yet available for commercial distribution in the USA. WaveCrest consists of a self-expanding nitinol frame covered by expanded polytetrafluoroethylene with 20 anchoring points that allow repositioning. WaveCrest was available in three sizes: 22, 27, and 32 mm. One unique feature of this device is its ability to perform distal contrast injection, which is useful for the assessment of occlusion and stability. Currently, the WAVECREST 2 trial is ongoing in the USA. The randomized controlled trial was designed to ensure that the safety and effectiveness of the WaveCrest device are comparable to those of the Watchman device.
LAmbre
The LAmbre LAA Closure System (Lifetech Scientific, Shenzhen, China) is a new self-expanding occluder composed of a nitinol mesh and polyester membrane with an umbrella and a cover connected by a short central waist. The LAmbre implant is available in 15 different sizes ranging from 16 to 36 mm based on the umbrella diameter. The device is delivered in 8- to 10-French sheaths and allows for complete recapture and repositioning within the LAA. The unique feature of the device is that it consists of a U-shaped anchor and hook stabilization system targeting the LAA trabeculae and pectoralis muscles. LAmbre received the CE mark on June 15, 2016. Huang et al. [58] reported the safety and effectiveness of the LAmbre device in a multicenter prospective study of 153 patients with AF and CHADS2 scores of ≥ 1. The LAA occlusion was successfully performed in 152 patients, and serious complications occurred in five patients. Ischemic stroke occurred in two patients, with incomplete LAA sealing in one patient, and no device embolization during the 12-month follow-up.
Ultrasept
The Ultrasept device (Cardia Inc., Eagan, MN, USA) is a novel, self-expandable, bulb-and-sail device intended to provide complete coverage of the LAA orifice. The device consists of a nitinol frame and distal cylindrical anchor, which are deployed and secured with a platinum/iridium collar and polyvinyl alcohol foam. The delivery sheath is currently available and ranges from 10 to 12 French. The Ultrasept device is fully retrievable, allowing it to be repositioned as many times as needed to ensure proper placement during deployment.
LARIAT
The LARIAT suture delivery device (SentreHEART, Redwood, California, USA) occludes the LAA via an epicardial suture and eliminates the need for a permanent implant inside the LAA. The procedure requires that a guide wire tipped with a magnet be inserted into the epicardium and endocardium after percutaneous puncture to deliver sutures for snipping the LAA at the epicardium. The device consists of a clever combination of a magnet-tipped wire that is placed in the endocardium via transseptal access and a second magnet-tipped wire that is placed in the epicardial space via pericardial access. The LARIAT device received a CE mark in 2009 and 510(k)-class II clearance in the USA. The LAA is a recognized source of sustained AF, and the LARIAT device contributes not only to the prevention of thromboembolic events but also to the improvement of AF ablation success. The LAALA-AF Registry demonstrated that the addition of LARIAT closure to a conventional AF ablation was beneficial in maintaining sinus rhythm in patients with persistent AF [59]. A total of 138 patients, with 69 in each group (the LARIAT group and the ablation-only group), were enrolled in the study. After one ablation procedure followed by 12 months of antiarrhythmic therapy, the rate of freedom from AF was 65% in the LARIAT group, compared with 39% in the ablation-only group (p = 0.002). This study revealed that LAA ligation with the LARIAT device for conventional ablation improves the outcome of AF ablation.
Future Directions and Conclusion
The prevalence of AF in the USA is estimated at 5.2 million and is projected to increase to 12.1 million by 2030 [60]. Therefore, it is essential to reduce the incidence of thromboembolic events in patients with AF. A growing body of evidence suggests that LAAC is a proven less invasive alternative procedure for long-term OAC in patients with AF at a high risk of bleeding. However, complications and OAC management after LAAC remain concern. Moreover, the LAA has a complex anatomical structure. The use of imaging modalities is beneficial for establishing procedural safety and simplicity. Recently, new-concept devices and design iterations have been developed to ensure the safety and efficacy of LAAC procedures, and many trials are under investigation (Table 6). With advancements in technology and operator experience, the LAAC procedure is expected to grow worldwide as a favorable treatment to address the unmet need for such treatments. It is expected that the number of patients with AF eligible for treatment with LAAC will increase. Further studies and upcoming trials are warranted in the future.
Data availability
The data that support the findings of this study are included in the manuscript or available from the corresponding author upon reasonable request.
References
Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke. 1991;22:983–8.
Stoddard MF, Dawkins PR, Prince CR, Ammash NM. Left atrial appendage thrombus is not uncommon in patients with acute atrial fibrillation and a recent embolic event: a transesophageal echocardiographic study. J Am Coll Cardiol. 1995;25:452–9.
Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61:755–9.
Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285:2864–70.
Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137:263–72.
Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138:1093–100.
Ernst G, Stöllberger C, Abzieher F, et al. Morphology of the left atrial appendage. Anat Rec. 1995;242:553–61.
Veinot JP, Harrity PJ, Gentile F, et al. Anatomy of the normal left atrial appendage: a quantitative study of age-related changes in 500 autopsy hearts: implications for echocardiographic examination. Circulation. 1997;96:3112–5.
Di Biase L, Santangeli P, Anselmino M, et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J Am Coll Cardiol. 2012;60:531–8.
Dallan LAP, Reed J, Yoon SH, et al. Novel cardiac magnetic resonance imaging-based sizing for left atrial appendage closure. J Cardiovasc Electrophysiol. 2022;33:2649–50.
Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367:1903–12.
Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009;360:2066–78.
Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994;154:1449–57.
Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med. 1999;131:492–501.
Savarese G, Giugliano RP, Rosano GM, et al. Efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation and heart failure: a meta-analysis. JACC Heart Fail. 2016;4:870–80.
Birman-Deych E, Radford MJ, Nilasena DS, Gage BF. Use and effectiveness of warfarin in medicare beneficiaries with atrial fibrillation. Stroke. 2006;37:1070–4.
Brass LM, Krumholz HM, Scinto JM, Radford M. Warfarin use among patients with atrial fibrillation. Stroke. 1997;28:2382–9.
Healey JS, Crystal E, Lamy A, et al. Left atrial appendage occlusion study (LAAOS): results of a randomized controlled pilot study of left atrial appendage occlusion during coronary bypass surgery in patients at risk for stroke. Am Heart J. 2005;150:288–93.
Dawson AG, Asopa S, Dunning J. Should patients undergoing cardiac surgery with atrial fibrillation have left atrial appendage exclusion? Interact Cardiovasc Thorac Surg. 2010;10:306–11.
Bakhtiary F, Kleine P, Martens S, et al. Simplified technique for surgical ligation of the left atrial appendage in high-risk patients. J Thorac Cardiovasc Surg. 2008;135:430–1.
Hernandez-Estefania R, Levy Praschker B, Bastarrika G, Rabago G. Left atrial appendage occlusion by invagination and double suture technique. Eur J Cardiothorac Surg. 2012;41:134–6.
Ram E, Orlov B, Sternik L. A novel surgical technique of left atrial appendage closure. J Card Surg. 2020;35:2137–41.
Salzberg SP, Emmert MY, Caliskan E. Surgical techniques for left atrial appendage exclusion. Herzschrittmacherther Elektrophysiol. 2017;28:360–5.
Ailawadi G, Gerdisch MW, Harvey RL, et al. Exclusion of the left atrial appendage with a novel device: early results of a multicenter trial. J Thorac Cardiovasc Surg. 2011;142(1002–9):1009.e1.
Whitlock RP, Belley-Cote EP, Paparella D, et al. Left atrial appendage occlusion during cardiac surgery to prevent stroke. N Engl J Med. 2021;384:2081–91.
Sievert H, Lesh MD, Trepels T, et al. Percutaneous left atrial appendage transcatheter occlusion to prevent stroke in high-risk patients with atrial fibrillation: early clinical experience. Circulation. 2002;105:1887–9.
Block PC, Burstein S, Casale PN, et al. Percutaneous left atrial appendage occlusion for patients in atrial fibrillation suboptimal for warfarin therapy: 5-year results of the PLAATO (percutaneous left atrial appendage transcatheter occlusion) study. JACC Cardiovasc Interv. 2009;2:594–600.
Bayard YL, Omran H, Neuzil P, et al. PLAATO (percutaneous left atrial appendage transcatheter occlusion) for prevention of cardioembolic stroke in non-anticoagulation eligible atrial fibrillation patients: results from the European PLAATO study. EuroIntervention. 2010;6:220–6.
Sick PB, Schuler G, Hauptmann KE, et al. Initial worldwide experience with the WATCHMAN left atrial appendage system for stroke prevention in atrial fibrillation. J Am Coll Cardiol. 2007;49:1490–5.
Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet. 2009;374:534–42.
Holmes DR Jr, Kar S, Price MJ, et al. Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014;64:1–12.
Reddy VY, Doshi SK, Kar S, et al. 5-year outcomes after left atrial appendage closure: from the PREVAIL and PROTECT AF trials. J Am Coll Cardiol. 2017;70:2964–75.
Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.
Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.
Osmancik P, Herman D, Neuzil P, et al. Left atrial appendage closure versus direct oral anticoagulants in high-risk patients with atrial fibrillation. J Am Coll Cardiol. 2020;75:3122–35.
Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage closure: results from the watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the continued access registry. Circulation. 2011;123:417–24.
Holmes DR Jr, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol. 2015;65:2614–23.
Reddy VY, Gibson DN, Kar S, et al. Post-approval U.S. experience with left atrial appendage closure for stroke prevention in atrial fibrillation. J Am Coll Cardiol. 2017;69:253–61.
Kar S, Doshi SK, Sadhu A, et al. Primary outcome evaluation of a next-generation left atrial appendage closure device: results from the PINNACLE FLX trial. Circulation. 2021;143:1754–62.
Paitazoglou C, Meincke F, Bergmann MW, et al. The ALSTER-FLX registry: 3-month outcomes after left atrial appendage occlusion using a next-generation device, a matched-pair analysis to EWOLUTION. Heart Rhythm. 2022;19:917–26.
Price MJ, Friedman DJ, Du C, et al. Comparative safety of transcatheter laao with the first-generation watchman and next-generation watchman FLX devices. JACC Cardiovasc Interv. 2022;15:2115–23.
Kapadia SR. Real-world outcomes with WATCHMAN FLX: early results from SURPASS. 2022. https://www.crtonline.org/presentation-detail/real-world-outcomes-with-watchman-flx-early-result
Freeman JV, Varosy P, Price MJ, et al. The NCDR left atrial appendage occlusion registry. J Am Coll Cardiol. 2020;75:1503–18.
Pison L, Potpara TS, Chen J, Larsen TB, Bongiorni MG, Blomström-Lundqvist C. Left atrial appendage closure-indications, techniques, and outcomes: results of the European Heart Rhythm Association Survey. Europace. 2015;17:642–6.
Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. 2016;18:1609–78.
Reddy VY, Möbius-Winkler S, Miller MA, et al. Left atrial appendage closure with the watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA plavix feasibility study with watchman left atrial appendage closure technology). J Am Coll Cardiol. 2013;61:2551–6.
Akashi S, Oguri M, Ikeno E, et al. Outcomes and safety of very-low-dose edoxaban in frail patients with atrial fibrillation in the ELDERCARE-AF randomized clinical trial. JAMA Netw Open. 2022;5:e2228500.
Della Rocca DG, Magnocavallo M, Di Biase L, et al. Half-dose direct oral anticoagulation versus standard antithrombotic therapy after left atrial appendage occlusion. JACC Cardiovasc Interv. 2021;14:2353–64.
Yerasi C, Lazkani M, Kolluru P, et al. An updated systematic review and meta-analysis of early outcomes after left atrial appendage occlusion. J Interv Cardiol. 2018;31:197–206.
Boersma LV, Ince H, Kische S, et al. Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-year follow-up outcome data of the EWOLUTION trial. Heart Rhythm. 2017;14:1302–8.
Aminian A, Lalmand J, Tzikas A, Budts W, Benit E, Kefer J. Embolization of left atrial appendage closure devices: a systematic review of cases reported with the watchman device and the amplatzer cardiac plug. Catheter Cardiovasc Interv. 2015;86:128–35.
Dukkipati SR, Holmes DR Jr, Doshi SK, et al. Impact of peridevice leak on 5-year outcomes after left atrial appendage closure. J Am Coll Cardiol. 2022;80:469–83.
Lempereur M, Aminian A, Saw J. Rebuttal with regards to “device-associated thrombus formation after left atrial appendage occlusion: a systematic review of events reported with the Watchman, the Amplatzer Cardiac Plug and the Amulet.” Catheter Cardiovasc Interv. 2018;92:E216–E217.
Fauchier L, Cinaud A, Brigadeau F, et al. Device-related thrombosis after percutaneous left atrial appendage occlusion for atrial fibrillation. J Am Coll Cardiol. 2018;71:1528–36.
Asmarats L, Cruz-González I, Nombela-Franco L, et al. Recurrence of device-related thrombus after percutaneous left atrial appendage closure. Circulation. 2019;140:1441–3.
Landmesser U, Schmidt B, Nielsen-Kudsk JE, et al. Left atrial appendage occlusion with the AMPLATZER Amulet device: periprocedural and early clinical/echocardiographic data from a global prospective observational study. EuroIntervention. 2017;13:867–76.
Lakkireddy D, Thaler D, Ellis CR, et al. Amplatzer amulet left atrial appendage occluder versus watchman device for stroke prophylaxis (amulet IDE): a randomized, controlled trial. Circulation. 2021;144:1543–52.
Huang H, Liu Y, Xu Y et al. Percutaneous left atrial appendage closure with the LAmbre device for stroke prevention in atrial fibrillation: a prospective, multicenter clinical study. JACC Cardiovasc Interv 2017;10:2188–94.
Lakkireddy D, Sridhar Mahankali A, Kanmanthareddy A, et al. Left atrial appendage ligation and ablation for persistent atrial fibrillation: the LAALA-AF registry. JACC Clin Electrophysiol. 2015;1:153–60.
Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112:1142–7.
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Nagasaka, T., Nakamura, M. Left Atrial Appendage Closure: A Narrative Review. Cardiol Ther 12, 615–635 (2023). https://doi.org/10.1007/s40119-023-00337-2
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DOI: https://doi.org/10.1007/s40119-023-00337-2