Abstract
Percutaneous left atrial appendage occlusion (LAAO) is recommended in several major international society guidelines as a viable alternative to therapeutic anticoagulation for the prevention of ischemic stroke in patients with nonvalvular atrial fibrillation or flutter. Recent innovations in device development have improved the safety and procedural success of LAAO, further fueling enthusiasm for expanding its indications beyond patients with high-bleeding risk from oral anticoagulation use. It is the aim of this review to provide historical context in addition to recent updates and upcoming developments and provide practical suggestions on how best to care for patients who are candidates for LAAO in contemporary practice. Recent data comparing the safety and efficacy of post-LAAO antiplatelet vs. antithrombotic therapy will be highlighted, with specific recommendations regarding which patients are best suited for each strategy. We will also address the safety and practical considerations provided by emerging trials on concomitant LAAO during other structural heart interventions such as transcatheter aortic valve replacement and mitral valve interventions, as well as electrophysiology procedures including catheter ablation for atrial fibrillation and pacemaker implantation. Practical considerations for the use of transesophageal echocardiography or intracardiac echocardiography for procedural guidance will also be discussed. As the evidence supporting LAAO continues to evolve, this review will serve as a primer on the recent and upcoming advances in device technology and management strategies positioned to further push LAAO forward into the future.
Highlights
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Left atrial appendage occlusion (LAAO) is safe and effective in reducing stroke patients with atrial fibrillation.
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New devices and techniques have dramatically improved the safety and efficacy of LAAO.
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LAAO is emerging as an alternative to oral anticoagulation in many patients with atrial fibrillation.
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Combined LAAO + structural/electrophysiology procedures may further improve safety and cost.
Introduction
In the pursuit of more effective stroke prevention strategies, percutaneous left atrial appendage occlusion (LAAO) has emerged as a compelling therapeutic strategy in patients with nonvalvular atrial fibrillation or flutter (NVAF) who are at increased risk of thromboembolic events and bleeding complications with the use of oral anticoagulants (OACs). While OACs have been the cornerstone for ischemic stroke prevention in NVAF for decades, adherence to OACs can be problematic due to bleeding complications, medication side effects, and cost, among other reasons. Certain studies indicate only approximately 50% of patients with an indication for OAC due to NVAF actually take an OAC, and among those that do, adherence is poor over long-term follow-up even with direct oral anticoagulants (DOACs). , Given this, and with the knowledge that more than 90% of atrial thrombi responsible for ischemic stroke in NVAF originate within the left atrial appendage (LAA), LAAO has found its role as an appealing alternative to OAC.
While early studies of LAAO focused on patients with a higher risk of stroke and bleeding complications, , progressive innovations in device technology, refinement of procedural techniques, and simplification of antithrombotic strategies post-LAAO have broadened the applicability of LAAO. The most recent generation of LAAO devices allows for implantation across a wider range of LAA anatomies with shorter procedural times and ease of implantation. They boast enhanced procedural safety, improved closure success rates, better outcomes, and improved patient satisfaction. Data that supports the risk/benefit ratio of LAAO has improved and is more favorable when evaluated over a longer time horizon, as the long-term complications of OAC use are additive and can be significant for up to 5 years.
Accordingly, this review will provide a practical summary of new developments in this rapidly evolving field and practical advice to providers considering LAAO for their patients. A focus will be placed on understanding the current and emerging indications for LAAO, contemporary data supporting LAAO use, and antithrombotic strategies. Emerging indications for LAAO including concomitant LAAO during structural heart procedures such as transcatheter aortic valve replacement (TAVR), mitral transcatheter edge-to-edge repair (M-TEER), transcatheter mitral valve replacement (TMVR), and concomitant LAAO at the time of electrophysiologic procedures including NVAF ablation will be highlighted. We will further discuss practical considerations regarding LAAO planning and procedural technique, including the use of computed tomography (CT) for screening, and intracardiac echocardiography (ICE) as an alternative to transesophageal echocardiography (TEE) for procedural guidance.
Current Indications for LAAO
International professional societal guidelines and expert consensus documents give percutaneous LAAO a Class IIA recommendation for prevention of ischemic stroke and systemic embolism in patients at risk for thromboembolic complications from NVAF and have a contraindication to long-term anticoagulation due to a nonreversible cause. , , , , It is also reasonable (Class IIb) in patients with high risk of major bleeding on OAC based on patient preference, with careful consideration of procedural risk. The currently approved indications for use of LAAO in the United States are provided in Table 1 , and approved devices in the United States are shown in Figure 1 . Indications for use are similar in the European Union, with the important exception that LAAO is approved in a broader segment of patients including those with true contraindications for OAC, while in the United States, patients must be able to tolerate short-term OAC or DAPT following the procedure.
| LAAO is indicated to reduce the risk of thromboembolism from the LAA in patients with NVAF who |
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Contraindications to percutaneous LAAO are summarized in Table 2 . These include the inability to tolerate short-term OAC or antiplatelet therapy post-LAAO, presence of another indication for anticoagulation given the lack of data demonstrating a benefit in addition to OAC, and anatomic exclusion for LAAO. The most common anatomic exclusions are the presence of thrombus in the LAA or shallow LAA anatomy with multiple lobes, which may not be fully covered by currently available LAAO devices ( Figure 2 with videos).
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Key Randomized Clinical Trials Supporting LAAO
A wealth of data supporting the use of percutaneous LAAO has been amassed from numerous randomized clinical trials (RCTs), observational studies, and required postapproval studies over the past 20 years.
The first LAAO device approved was the WATCHMAN 2.5 (Boston Scientific, Marlboro, Massachusetts), which has since iteratively improved as the WATCHMAN-FLX and WATCHMAN-FLX PRO. The pivotal clinical trials that led to the approval of index device as an alternative to warfarin were PROTECT-AF and PREVAIL. A third trial, PRAGUE-17, was published in 2020 and affirmed noninferiority of the WATCHMAN 2.5 and WATCHMAN-FLX or Amulet devices to OAC with a DOAC agent. A high-yield summary of the key findings of these trials is provided in Table 3 .
| PROTECT AF | PREVAIL | Amulet IDE | PRAGUE-17 | |
|---|---|---|---|---|
| Comparison | WATCHMAN vs. warfarin | WATCHMAN vs. warfarin | Amulet vs. WATCHMAN | WATCHMAN 2.5 or WATCHMAN-FLX or Amulet vs. NOAC (apixaban, rivaroxaban, dabigatran) |
| Design | Noninferiority | Noninferiority | Noninferiority | Noninferiority |
| Sample size | 2:1 device:control randomization | 2:1 device:control randomization | 1:1 randomization to Amulet or WATCHMAN 2.5; 1878 patients | 201 LAAO vs. 201 NOAC |
| 463 LAAO vs. 244 warfarin | 269 LAAO vs. 138 warfarin | |||
| Patient population | CHADS2 ≥1 | CHADS 2 ≥2 and 1 other risk factor (high-risk) | CHADS 2 ≥2 or CHA 2 DS 2 -VASc ≥3 | CHA 2 DS 2 -VASc ≥3 |
| HAS-BLED ≥3 | ||||
| Primary Endpoint | Efficacy: composite CVA, SE, CV death | 1st co-primary endpoint: composite CVA, SE, CV/unexplained death | Primary safety endpoint: procedure-related complications, all-cause death, major bleeding through 12 mo. | Composite CVA, TIA, SE, CV death, major or nonmajor bleed, procedure/device complications |
| Safety: major bleeding, pericardial effusion, device embolization | 2nd co-primary endpoint: late ischemic events (CVA or SE > 7 d) | Primary efficacy endpoint: ischemic stroke, SE through 18 mo. | ||
| 3rd co-primary endpoint: early safety events (all-cause death, ischemic CVA, SE, device/procedure complications | ||||
| Follow-up | 1065 patient-years | 18 mo | 18 mo | 19.9 mo |
| Key results | Efficacy—WATCHMAN noninferior to warfarin: 3 per 100 patient years vs. 4.9 per 100 patient years (RR 0.35-1.25) | 1st co-primary endpoint similar between WATCHMAN (0.064) and warfarin (0.063) but noninferiority not technically met (RR 1.07) | Amulet noninferior to Watchman for safety and efficacy. | No differences in composite (10.99% vs. 13.42%; sHR 0.53-1.31) or any component of composite between LAAO and NOAC |
| Safety: 7.4 per 100 patient years vs. 4.4 per 100 patient years (RR 1.01-3.19) | 2nd co-primary endpoint of late ischemic events noninferior | Complete LAAO higher with Amulet vs. Watchman (98.9 vs. 96.8%; p = 0.003). | ||
| Procedure complications higher with Amulet (4.5% vs. 2.5%), driven by pericardial effusion. | ||||
| Other important points | First generation device; safety/efficacy improved with device improvements | Fewer safety events than PROTECT AF (4.2% vs. 8.2%; p -0.004) (3rd co-primary endpoint) | Older generation Watchman 2.5 device used | 4.5% LAAO complication rate |
The headline results of these RCTs evaluated Watchman at 1.5 years approximately. Long-term efficacy and safety outcomes after LAAO have remained favorable, and they show that the benefits of LAAO further accumulate over time as a significant reduction of major bleeding events. , In this regard, in a pooled analysis out to 5 years, including 1114 patients treated with WATCHMAN 2.5 in PROTECT-AF and PREVAIL, LAAO had similar rates of composite stroke, systemic embolism (SE), or cardiovascular/unexplained death as warfarin (hazard ratio [HR] 0.820, p = 0.27). However, LAAO had less hemorrhagic stroke (HR 0.20, p = 0.0022), disabling/fatal stroke (HR 0.45, p = 0.03), and postprocedure bleeding (HR 0.48, p = 0.0003) than OAC. As a result, cardiovascular death (HR 0.59, p = 0.027), and all-cause death (0.73; p = 0.035) were lower with LAAO when patients were followed in the long-term.
Data from these RCTs indicate excellent short-, medium-, and long-term results with LAAO compared to OAC with warfarin or DOAC agents. They confirm that the benefits of LAAO accumulate over the lifetime of the patient, including a significant reduction in major bleeding events and a potential reduction in cardiovascular and all-cause mortality over OAC strategies.
Device Developments: WATCHMAN-FLX Series
Considering these initial RCT data, the US Food and Drug Administration (FDA) approved the WATCHMAN 2.5 device in April 2015. Subsequently, postmarket registry and large observational studies have confirmed the safety and efficacy of this first-generation WATCHMAN 2.5 device.
Recent studies have further shown improved clinical outcomes with the next generation WATCHMAN-FLX device, owing to significant changes in device design that improve the safety of deployment by less risk of trauma to the LAA, better LAA closure rates, and less device-related thrombus (DRT). Figure 1 provides key features of the design of the WATCHMAN 2.5 as a comparator to the newer WATCHMAN-FLX. Improvements to the WATCHMAN-FLX design include both larger available diameters as well as a shallower device at all sizes, a larger polytetrafluoroethylene cover to reduce metal exposure, an 18 strut frame to improve tissue contact and seal, two rows of 9 anchors, each with a less traumatic design to improve tissue engagement, and a closed distal tip to improve the safety. A key step in the deployment of the WATCHMAN-FLX is formation of the WATCHMAN FLX ball, as in partial deployment, the device forms a minimally traumatic “ball” without any sharp edges and can be advanced safely and maneuvered within the LAA to achieve an optimal position and seal. This increased maneuverability allows for better coverage of challenging anatomies, including selection of the optimal distal lobe and coverage of proximal lobes. The device is fully recapturable at any step of deployment prior to release. The delivery sheath has also been improved to be more maneuverable and is now integrated with the transseptal puncture system as the WATCHMAN Connect.
The PINNACLE FLX study and subsequent data from the NCDR LAAO registry (SURPASS) have confirmed the superiority of the WATCHMAN-FLX device over the prior WATCHMAN 2.5. , PINNACLE FLX was a prospective, nonrandomized registry of 400 patients treated with the WATCHMAN-FLX device and confirmed a 100% LAA closure rate with WATCHMAN-FLX (defined as ≤5 mm peridevice leak [PDL] at 12 months). There was further reduction in DRT compared to rates seen with WATCHMAN 2.5. , In real-world data from the SURPAASS registry of 16,445 patients treated with WATCHMAN FLX, procedural success was excellent at 97.6%. Safety was excellent, with only 0.37% of patients experiencing a device or procedure-related event (all-cause death, stroke/SE, device/procedure complication) and more patients with a complete seal (95% with PDL <3 mm). WATCHMAN FLX patients also had comparatively lower mortality (0.91%), ischemic stroke (0.28%), pericardial effusion requiring intervention (0.51%), and DRT (0.23%).
Considering these data, FDA approval of the WATCHMAN FLX device was obtained in July 2020. The FLX device has since been used in nearly 190,000 of the total 300,000 WATCHMAN procedures completed. In September 2023, the WATCHMAN FLX Pro was released, consisting of an enhanced polymer coating designed to promote faster healing and endothelization of the device surface, markers for better visualization during fluoroscopic deployment, and a new 40 mm size device to treat larger LAA diameters ( Figure 1 ).
Recent Device Developments: Amulet
The Amplatzer Amulet device (Abbott) consists of two elements: a distal lobe that sits in the LAA and a disc that fully covers the LAA ostium ( Figure 1 ). A single row of stabilization hooks protrudes from the distal lobe to anchor the device in the LAA. The anchoring lobe is flexible and conforms to most LAA anatomies within the range specified for size of device. The anchoring lobe and covering disc articulate separately, which allows for treatment of complex LAA anatomies with multiple lobes or proximal lobes that may be difficult to cover.
In 2021, the FDA approved the Amplatzer Amulet device for the same indications as WATCHMAN. This was based on the results of the Amulet IDE trial, which randomized 1878 high-risk patients to LAAO with Amulet vs. WATCHMAN 2.5 and found the Amulet device was noninferior to WATCHMAN 2.5 regarding safety and efficacy of stroke prevention. There was, however, slightly superior success for LAA occlusion with Amulet vs. WATCHMAN 2.5 (98.9% vs. 96.8%, p = 0.003 for superiority), with more patients with a complete seal (63% vs. 46%), though there was no significant difference in significant PDL >5 mm at 45 days (1% vs. 3%). There was slightly more pericardial effusion up to 10 days with the Amulet device, the time course for which differed in comparison to the WATCHMAN 2.5, for which most of these events occurred within 24 hours. It should be noted that DAPT was used in the Amulet group, while patients with WATCHMAN 2.5 were treated with OAC + aspirin as per the FDA instructions for use.
Data from the 5499 patients who underwent Amulet LAAO in the NCDR LAAO Registry indicates a slightly lower major adverse event rate than the IDE trial of 5.7% out to 45 days, mainly driven by major bleeding and pericardial effusion. These findings are supported by results from a large multicenter registry with 2-year follow-up, as well as long-term follow-up data from the PRAGUE-17 trial to 4 years.
Data Comparing LAAO Devices
Given the results of the Amulet IDE, which showed superiority to WATCHMAN 2.5 with regard to seal and PDL, there was impetus to compare the Amulet device to the newer WATCHMAN FLX device. The SWISS-APERO trial was a 3-way comparison of LAAO with the Amulet (111 patients), WATCHMAN 2.5 (25 patients), or WATCHMAN FLX (85 patients) in eight European centers. The trial found no difference in the primary endpoint of composite crossover to a nonrandomized device during the procedure or residual LAA patency detected by CT at 45 days between devices. Likewise, there was no difference in composite cardiovascular death, stroke, or SE between Amulet or WATCHMAN patients. However, similar to the Amulet IDE, there was more major bleeding and pericardial effusion with Amulet than WATCHMAN (9.0% vs. 2.7%; p = 0.047). Small PDLs were more frequent with TEE in WATCHMAN patients but were more common with cardiac computed tomography angiography with Amulet. Nevertheless, there were no clinically significant PDLs >5 mm. Data from large postapproval registries of Amulet and WATCHMAN FLX are shown in Table 4 . The takeaway message is that either WATCHMAN FLX or Amulet achieve success, and either device is an excellent choice for LAAO.
| Emerge LAA | PINNACLE FLX | SURPAASS | |
|---|---|---|---|
| Comparison | Amulet postapproval registry | WATCHMAN FLX postapproval registry | WATCHMAN FLX outcomes from NCDR LAAO Registry |
| Sample size | 5499 patients | 400 patients | 16,446 |
| Implant success | 95.8% | 100% | 97.6% |
| Complete occlusion at 45 d | 87.1% | 100% | |
| Major adverse events at 45 d | |||
| PE requiring intervention | 1.9% | 0.7% | 0.5% |
| Device embolization | 0.2% | 0% | 0.03% |
| Stroke | 0.3% | 0.7% | 0.4% |
| Death | 1.0% | 0.5% | 0.9% |
| Other important points | Less PE req intervention at 45 d with improved operator experience (1.5 vs. 2.3%; p = 0.012). | 0.5% primary safety event; significantly below performance goal 4.2%. | Similar event rates as PINNACLE FLX. Early results; full data not yet published. |
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