Addressing Peri-Device Leaks in Next-Generation Transcatheter Left Atrial Appendage Occluders: An Open Question

Abstract

With FDA-approved devices, left atrial appendage (LAA) occlusion has emerged as a well-established and rapidly growing approach to stroke prevention in patients with non-valvular atrial fibrillation. These devices are indicated for use in patients who are at increased risk of stroke and systemic embolism, as determined by CHA₂DS₂-VASc scores, and are suitable for anticoagulation therapy, with an appropriate rationale for seeking a non-pharmacologic alternative. This includes patients who may be unsuitable for long-term anticoagulation due to contra-indications. These devices, generally consisting of a nitinol-framed structure with a circular cross-section, are positioned within the LAA to obstruct the ostium, effectively preventing the thrombus from embolizing the brain. The initial clinical data from pivotal trials and observational registries indicated no strong correlation between peri-device leaks (PDLs) and adverse events. However, recent studies have shown that PDLs are associated with a higher risk of thrombo-embolic events, leading to renewed interest in managing PDLs. This paper reviews the occurrence of PDLs after percutaneous LAA occlusion using current FDA-approved devices, highlighting the need for non-circular occluders to better-accommodate the inherent variability in LAA anatomy. It also compares the benefits and limitations of emerging approaches still under investigation, focusing on addressing PDLs.

1. Introduction

1.1. Left Atrial Appendage and Stroke Prevention in Patients Experiencing Atrial Fibrillation

Atrial fibrillation (AF), which promotes the formation of blood clots, significantly increases the risk of ischemic stroke, rendering it up to 3-to-5-times higher compared to the general population [1,2,3]. The use of warfarin and/or oral anticoagulants (OACs) is currently the treatment of choice to reduce the risk of stroke [4,5,6,7]. However, only half of the patients experiencing AF are adequately anticoagulated, due to several factors [8]. These factors include concerns about bleeding risks, difficulties with medication adherence, drug–drug interactions, the need for regular monitoring with warfarin, and dietary restrictions [9]. This therapy is systemic and increases the risk of bleeding [10]. Therefore, researchers and clinicians are increasingly exploring innovative approaches that focus on the localized prevention of thrombi formation within the left atrium, with the aim of providing an alternative to systemic anticoagulation therapies. It has been reported that the left atrial appendage (LAA) is the source of stroke for more than 90% of thrombi in patients with non-rheumatic AF [11,12].

The LAA is a small pouch-shaped chamber located in the muscular wall of the left atrium of the heart. This appendage can become problematic when the atrium fails to contract properly. In such cases, blood flow within the LAA may slow down significantly or even stagnate, creating conditions suitable for clot formation. The LAA is not merely an anatomical structure but serves important physiological functions through its complex interactions with the left atrium. It acts as a decompression chamber during left atrial pressure overload and contributes to left atrial reservoir function through its enhanced distensibility. The LAA also plays a crucial role in volume homeostasis through the secretion of atrial natriuretic peptide (ANP) [13]. During normal sinus rhythm, the LAA contracts vigorously, contributing to left atrial booster pump function and enhancing left ventricular filling. These physiological functions highlight why LAA occlusion must consider not only anatomical fit but also the hemodynamic consequences of device placement. Alterations in these natural hemodynamic interactions may contribute to PDL formation through changes in local flow patterns and pressure distributions. This situation is particularly concerning, because blood clots that develop in this area can potentially lead to severe complications if they break free and enter the bloodstream. Stroke occurs when these clots are dislodged out of the heart and into the brain. Surgical interventions to manipulate and modify the LAA’s structure, termed LAA closures, have been employed since the 1930s [14]. These procedures prevent thrombus formation within the appendage and mitigate embolism risks. By modifying the LAA anatomy, physicians seek to reduce the possible complications associated with this cardiac structure in high-risk patients. Over the past ten years, research has increasingly documented the safety and effectiveness of LAA occlusion [15,16,17,18,19,20]. However, some studies have identified ongoing concerns that necessitate further exploration to evaluate the effectiveness of LAA closure interventions [21,22,23,24,25]. One of these complications is incomplete LAA occlusion, often referred to as a residual leak or peri-device leak (PDL) [26]. While the initial data from LAA occlusion trials and observational studies suggested no clear link between PDLs and complications [27,28], recent research has prompted re-evaluating this association [29,30].

LAA closure can be achieved through surgical and percutaneous catheter-based approaches [31]. Surgical occlusion of the LAA is the standard approach for patients undergoing mitral valve repair/replacement or maze surgery and is also recommended for those undergoing coronary bypass surgery [32,33]. Despite evidence showing that excluding the LAA from blood circulation can effectively reduce the risk of the formation of thrombus and subsequent stroke in patients experiencing AF, many surgeons are hesitant to perform this procedure. Several factors contribute to incomplete surgical LAA closure. First, the complex and variable anatomy of the LAA, including its trabeculated inner surface and multiple lobes, makes achieving complete closure technically challenging. Second, the thin and delicate nature of the LAA wall tissue can make it susceptible to tearing during surgical manipulation, leading surgeons to be more conservative in their closure technique. Third, the limited surgical exposure and visualization of the LAA base during conventional cardiac procedures can impair optimal closure. Fourth, different surgical techniques (such as suturing, stapling, or excision) each have their own limitations. For example, sutures can loosen over time, staples may not completely compress the tissue, and excision might leave a residual stump. Additionally, anatomical variations in the relationship between the LAA and surrounding structures, particularly the circumflex coronary artery, may force surgeons to modify their closure technique to avoid injury to these critical structures. This hesitancy is primarily due to the high risk of incomplete closure of the LAA, which can lead to blood leakage. Studies have shown that incomplete LAA closure not only diminishes the procedure’s effectiveness but also increases the risk of stroke from 2% to as high as 24% [14]. Recently, several less invasive percutaneous techniques for LAA occlusion have been developed and approved by the U.S. Food and Drug Administration (FDA). Although these devices are safe [34] and effectively reduce the risk of stroke when compared to no treatment [35], their effectiveness is not superior to medicinal treatment with OAC [28,36,37,38].

While potentially effective, these procedures for LAA occlusion come with their own risks, such as bleeding complications, infection, and damage to the surrounding cardiac structures [39]. These significant procedural risks often lead healthcare providers to keep patients on OAC as a precautionary measure, even after LAA occlusion. However, this continued use of anticoagulants undermines the primary goal of the procedure, which is to reduce or eliminate the need for long-term anticoagulation therapy. Consequently, patients may find themselves facing both the risks associated with the intervention procedure and the ongoing challenges of anticoagulant use, including potential bleeding complications. On the other hand, while FDA-approved transcatheter LAA occluder devices, such as WATCHMAN FLX (Boston Scientific, Marlborough, MA, USA) and Amplatzer Amulet (Abbott, Minneapolis, MN, USA), demonstrate a success rate exceeding 90% [40,41,42], they come with drawbacks, including incomplete LAA closure, which has been reported to affect approximately 25% of patients, resulting in a persistent need for OAC and leading to adverse outcomes such as thrombo-embolic events, device-related thrombosis, and increased risk of bleeding due to continued anticoagulation therapy [26]. With the promise of transcatheter LAA closure for the growing population of AF patients [43], innovation must continue to develop devices that best mitigate PDL implications. Figure 1 shows the location and anatomy of the LAA and its role in clot formation during AF caused by abnormal electrical activity [44]:

1.2. Definition and Implications of Persistent PDL

PDLs have been the subject of long-term clinical debate since the first transcatheter LAA occlusions [45]. Until recently, few comprehensive studies have examined the relationship between PDLs and clinical outcomes. However, the existing findings were constrained by two main challenges. First, since strokes are rare after LAA occlusion, a study with sufficient statistical power requires a large patient cohort. Second, patients with significant leaks (≥5 mm) are typically kept on anticoagulation therapy, introducing a treatment bias aimed at safeguarding their health. Moreover, the effects of smaller leaks (≤5 mm), which occur more frequently, have only recently begun to receive proper attention [30].

Moreover, ambiguity surrounds the definition of clinically significant PDLs, mainly because of multiple factors that complicate standardization and clinical decision making. The pathophysiologic mechanisms underlying PDL development after initial closure are multifactorial. In device-based closure, PDLs can develop through several mechanisms: (1) dynamic tissue remodeling around the device, where the LAA tissue undergoes progressive changes in response to mechanical stress; (2) device compression-induced tissue atrophy, potentially creating new gaps between the device and the LAA wall; (3) cyclic loading from cardiac contraction that may gradually alter device positioning or tissue configuration; (4) left atrial pressure variations that can deform the LAA-device interface, particularly during conditions that elevate left atrial pressure, such as heart failure exacerbations or hypertensive episodes; and (5) individual variation in endothelialization patterns around the device. In surgical closure, incomplete healing, suture loosening, or tissue dehiscence can lead to PDL formation over time. The complex trabeculated anatomy of the LAA can also mask residual communications that become more apparent as tissue remodeling occurs. Understanding these pathophysiologic mechanisms is crucial for developing more effective closure strategies and identifying patients at higher risk for PDL development.

Also, uncertainty exists regarding the size threshold for significance, with expert guidelines often utilizing an arbitrary cutoff of 5 mm to distinguish between significant and non-significant leaks. At the same time, some studies consider leaks as small as 3 mm to be clinically relevant [46]. This variability in size criteria is further compounded by the timing of PDL assessment, which can range from early postoperative imaging at 2–3 months to later follow-ups at one year or beyond, introducing temporal inconsistencies, as leaks may evolve, persist, or resolve over time. The complexity of defining significant PDLs is exacerbated by the imperfect correlation between leak size and clinical impact, with more minor leaks potentially causing significant symptoms in some patients, while larger leaks may remain asymptomatic in others. This lack of consensus impacts clinical management and hinders research comparability and the development of evidence-based guidelines, underscoring the pressing need for standardized, clinically relevant criteria that account for both the size and the temporal aspects of PDLs, to improve patient care and advance the field.

Building upon the complex pathophysiologic mechanisms of PDL development, the process of PDL resolution presents an equally challenging landscape. The mechanisms underlying PDL resolution are multifaceted and not yet fully understood. Potential contributing factors include: (1) dynamic tissue remodeling, where LAA tissue progressively adapts to the device through mechanical stress-induced changes; (2) the endothelialization process, where cellular growth gradually covers the device–tissue interface, potentially sealing small gaps; (3) hemodynamic adaptations, including potential alterations in left atrial pressure and flow dynamics that may contribute to leak reduction; and (4) biological tissue response, involving inflammatory and repair mechanisms that might facilitate device integration. The interplay of these mechanisms suggests a complex, time-dependent process of PDL resolution that warrants further comprehensive investigation.

1.3. Imaging Modalities for PDL Detection

Cardiac computed tomography (CT) has emerged as the gold standard for PDL detection, offering superior sensitivity and detailed three-dimensional assessment of residual leaks. This is evidenced by comparative studies showing CT detects significantly more PDLs compared to TEE in post-implantation evaluations [27]. While TEE remains essential for procedural guidance and initial assessment, CT provides more comprehensive evaluation of PDL presence, size, and morphology. The superiority of CT stems from its ability to provide high-resolution, multi-planar imaging that can detect even small leaks that might be missed by other imaging modalities. Additionally, CT allows precise measurement of leak dimensions and assessment of the spatial relationship between the device and LAA anatomy, which is crucial for planning any potential interventions for PDL closure.

There has yet to be an agreement on the best approach for detecting and measuring PDLs. It is commonly defined as a remaining connection between the left atrium and the LAA, as determined by a trans-esophageal echocardiogram (TEE) or cardiac CT [47,48]. Studies have demonstrated investigational bias in PDL detection, with notable differences between local site assessments and core laboratory evaluations [49,50]. Local site investigators tend to report lower PDL rates compared to independent core laboratories, potentially due to differences in evaluation criteria, expertise levels, and inherent procedural success bias. This variance is particularly evident in clinical trials, where core laboratory adjudication consistently identifies higher rates of PDLs compared to site-reported outcomes. For instance, in large-scale registries, local site evaluations have reported PDL rates as low as 8–10%, while core laboratory assessments in randomized trials have identified rates exceeding 30%, using identical imaging modalities. These discrepancies highlight the importance of standardized evaluation protocols and independent assessment to minimize investigational bias in PDL detection.

High-quality TEE imaging is essential for accurate device sizing, optimal trans-septal puncture location, and real-time guidance during deployment. A comprehensive evaluation should include multiple TEE views (0°, 45°, 90°, and 135°) to fully assess LAA morphology and dimensions. Three-dimensional (3D)-TEE with multi-planar reconstruction provides superior anatomical visualization and precise measurements compared to 2D imaging alone. This is particularly critical for complex anatomies where standard views may be suboptimal. Intra-procedural TEE guidance ensures proper device positioning and compression, while color Doppler imaging immediately detects any residual leaks that may require repositioning. Post-deployment TEE assessment should systematically evaluate device stability, position relative to surrounding structures, and seal completeness by carefully inspecting the device–tissue interface, using multiple angles and imaging modalities. Pre-procedural TEE assessment of LAA morphology is also critical for successful device selection and procedural planning. A comprehensive morphological evaluation should also characterize the LAA shape (e.g., chicken wing, cactus, windsock, or cauliflower), assess ostial dimensions at multiple angles, and measure the depth and orientation of the main lobe and any additional lobes. This detailed morphological assessment guides the device type and size choice, to achieve optimal LAA occlusion.

Also, intracardiac echocardiography (ICE) is employed to guide LAA closure and has proven to be an effective tool for guiding the procedure and accurately detecting PDLs, due to its high-resolution imaging that provides detailed visualization of the LAA, which is essential for identifying any residual communication [51,52]. However, the reported prevalence of PDL shows considerable variation depending on the imaging modality used for assessment. While TEE has been employed to identify PDLs in clinical trials [47,53,54], several studies indicate that CT is a more sensitive technique for assessing PDLs in comparison to TEE [55,56,57]. CT provides a detailed assessment of the shape, size, and function of PDLs, whereas TEE primarily measures dimensions based on the widths of the color Doppler jet. In a study of 346 patients who underwent both TEE and CT imaging eight weeks after LAA occlusion with an Amplatzer device, TEE identified a visible gap in 110 patients (32%), while CT detected gaps in 210 patients (61%) [27]. While imaging modalities are widely used for PDL detection, direct correlation studies between imaging findings and patho-anatomic or surgical verification remain limited. The few available surgical series mainly come from cases where PDLs required reintervention, potentially introducing selection bias. In these cases, CT and TEE findings generally showed fair correlation with surgical observations of leak location and size [27,56]. However, systematic studies comparing imaging findings with pathologic specimens are lacking, primarily due to the limited availability of post-mortem specimens from patients with LAA occlusion devices. This represents an important knowledge gap in validating our current imaging criteria for PDL assessment. Future research combining advanced imaging with surgical or pathological correlation would be valuable for establishing more precise diagnostic criteria and improving our understanding of PDL morphology.

Successful LAA occlusion and PDL prevention requires precise attention to pre-procedural planning and device sizing through comprehensive TEE assessment. Recent work by Bonanni et al. has demonstrated that integrating both 2D and 3D TEE measurements, particularly during critical steps like trans-septal puncture, significantly impacts procedural success [58]. Their standardized approach to TEE-guided measurements highlights how proper imaging techniques influence device selection and positioning outcomes. To achieve perpendicular device alignment, the assessment must account for LAA ostial dimensions, morphology variations, and optimal puncture location. Improper sizing or suboptimal positioning can create gaps between the device and the LAA wall, leading to PDL formation. The relationship between imaging guidance and PDL prevention extends beyond simple dimensional measurements. As shown, successful occlusion requires precise alignment achieved through optimal trans-septal puncture height and posterior orientation. Integrating 3D-TEE with multi-planar reconstruction provides superior anatomical visualization throughout the procedure.

Della Rocca et al. in [59] demonstrated that 3D-ICE provides superior visualization and measurement accuracy compared to traditional 2D imaging modalities for LAA assessment. The high correlation between pre-procedural TEE and periprocedural 3D-ICE measurements suggests that 3D-ICE could potentially eliminate the need for pre-procedural TEE screening. Furthermore, 3D-ICE showed significantly better agreement with final device sizing (96.3% vs. 80.4%, p = 0.005) compared to 2D-ICE, leading to fewer device recaptures and repositioning attempts. This enhanced accuracy in device selection and positioning could theoretically reduce PDL rates, though larger randomized studies are needed to confirm this benefit. Also, a comprehensive meta-analysis of 42,474 patients provided important insights into the comparative effectiveness of imaging modalities for LAA [60] occlusion. While ICE demonstrated higher procedural success compared to TEE, it was associated with higher rates of pericardial effusion and residual iatrogenic atrial septal defect. The regional variations in procedural success with ICE highlight the importance of operator experience and learning curve. These findings suggest that while ICE may offer certain procedural advantages, its adoption should be accompanied by proper training and case selection to minimize complications that could lead to incomplete LAA closure and PDL. Figure 2 shows PDLs observed through TEE and cardiac CT angiography (CCTA), highlighting the key imaging features essential for identifying PDLs during follow-up assessments [57].

1.4. PDL Incidence in Patients Experiencing AF

The recently published OPTION trial has provided compelling evidence for an alternative approach to stroke prevention in patients undergoing AF ablation [61]. In this international randomized trial of 1600 patients with elevated stroke risk (CHA₂DS₂-VASc score ≥2 in men and ≥3 in women), LAA closure demonstrated superior safety outcomes compared to OAC while maintaining equivalent efficacy in stroke prevention. The study revealed a significantly lower rate of non-procedure-related major bleeding or clinically relevant non-major bleeding in the LAA closure group (8.5%) compared to the anticoagulation group (18.1%) (hazard ratio, 0.44; 95% CI, 0.33–0.59; p < 0.001). Device implantation success rate was 98.8%, with complete LAA seal observed in 81.0% of patients at 3 months and 79.7% at 12 months, indicating a PDL rate of approximately 20%. Late PDL data beyond 12 months were not specifically reported in the trial. The trial’s findings are particularly noteworthy, given that 95% of patients received direct OAC rather than warfarin, reflecting contemporary clinical practice.

Several other studies have indicated that incomplete closure frequently occurs following transcatheter LAA occlusion [29]. However, the clinical significance and approach to managing PDLs still need to be fully understood [62]. In the Amulet IDE trial, which assessed the Amplatzer Amulet LAA occluder, the rates of any PDL and PDLs measuring 3 mm or more at the 45-day mark were 37.0% (296 out of 801 patients) for those treated with the Amulet device (Abbott Vascular). In the PROTECT AF trial, which investigated the WATCHMAN LAA System for embolic protection in patients with AF, 40.9% of patients had any PDL detected on the 45-day TEE, while 13.3% had a PDL ≥ 3 mm [28]. In comparison, the incidence rates for patients receiving the WATCHMAN 2.5 device were 53.9% (427 out of 792 patients) for any PDL and 25.9% (205 out of 792 patients) for PDLs ≥ 3 mm [53]. The differences in PDLs between the WATCHMAN 2.5 and Amulet devices could affect the frequency of ischemic events. The Amulet IDE trial data revealed no significant difference in ischemic stroke or systemic embolism rates between the two devices at 18 months, with both reporting a rate of 2.8%, despite the WATCHMAN device exhibiting a higher incidence of PDLs.

Additionally, prospective registries have documented lower PDL rates for both the WATCHMAN and Amulet devices compared to randomized controlled trials (RCTs). For instance, the EWOLUTION study, which included 835 patients, reported that 8.4% had a PDL of any size at the 45-day follow-up [49,63]. Similarly, in the global Amulet observational study, which included 1088 patients treated with the Amulet device, the rate of any PDL adjudicated by the core laboratory at the 45-day mark was recorded at just 9.9% [50]. Analysis of data from over 50,000 patients in the U.S. National Cardiovascular Data Registry (NCDR) revealed that 26.6% of patients had a PDL of any size 45 days after LAA occlusion with the WATCHMAN 2.5 device, as identified through follow-up TEE [26]. In comparison, the PINNACLE FLX registry, involving 400 patients, reported a lower 17.4% incidence of any PDL at 45 days for the WATCHMAN FLX device [64]. Similarly, the SURPASS registry, which included 16,048 patients treated with the WATCHMAN FLX device, found a comparable PDL rate of 18.0% at the 45-day follow-up.

Temporal changes in PDL occurrence and size of PDLs have been noted in up to 25% of patients who initially presented with detectable leaks following LAA occlusion. In the PROTECT AF trial, the percentage of patients with any PDL decreased from 40.9% to 32.1% over the course of one year [28]. Similarly, the Amulet IDE trial reported a decrease in PDLs of 3 mm or more from 25.9% to 21.7% in the WATCHMAN group, and from 11.2% to 9.5% in the Amulet group, between 45 days and one year. Additionally, new PDLs of 3 mm or greater were identified at one year in 8.3% of the WATCHMAN group and 4% of the Amulet group [65]. In the PINNACLE FLX study, the rate of any PDL decreased from 17.4% at 45 days to 10.5% at one year [64]. Additionally, a CT-based analysis of LAA occlusion using Amplatzer devices revealed that the LAA’s contrast patency rate decreased from 66% at two months to 47% at one year [66]. Cross-trial comparison of PDL rates reveals notable differences between devices and study settings. In RCTs, the WATCHMAN device showed PDL rates of 40.9% at 45 days in PROTECT AF, while the Amulet IDE trial reported lower rates of 37.0% for Amulet versus 53.9% for WATCHMAN 2.5. However, real-world registries demonstrated significantly lower PDL incidence: EWOLUTION reported 8.4% for WATCHMAN, the global Amulet observational study showed 9.9%, and the SURPASS registry found 18.0% for WATCHMAN FLX. These variations can be attributed to several factors: (1) differences in imaging protocols and PDL detection methods between trials, with CT showing higher sensitivity than TEE (61% vs. 32% in comparative studies); (2) evolution of device designs and delivery techniques; and (3) varying definitions of clinically significant PDLs across studies, ranging from any visible leak to those ≥3mm.

A comparison of PDL incidence across major clinical trials is presented in

Table 1. Comparison of PDL incidence across major clinical trials.

Study	Device	Number of Patients	Assessment Timing	PDL Definition	PDL Rate (%)
OPTION Trial	WATCHMAN FLX	803	3 months	Any PDL	19.0%
			12 months		20.3%
Amulet IDE	Amplatzer Amulet	801	45 days	Any PDL	37.0%
				PDL ≥ 3 mm	11.2%
PROTECT AF	WATCHMAN	485	45 days	Any PDL	40.9%
				PDL ≥ 3 mm	13.3%
WATCHMAN 2.5 Registry	WATCHMAN 2.5	792	45 days	Any PDL	53.9%
				PDL ≥ 3 mm	25.9%
PINNACLE FLX	WATCHMAN FLX	400	45 days	Any PDL	17.4%
			12 months		10.5%
SURPASS	WATCHMAN FLX	16,048	45 days	Any PDL	18.0%

. This systematic presentation highlights the variability in PDL rates between different devices and assessment timepoints, as well as the evolution of PDL rates with newer-generation devices. Notably, the definition and assessment methods for PDLs have varied across studies, making direct comparisons challenging.

2. Current Solutions for LAA Closure

Adverse outcomes from PDL can lead to a variety of clinical complications if left untreated. These persistent leaks can contribute to higher prevalence of cardiomyopathy [38], permanent AF [18], large LAA diameters [27], thrombo-embolic events [21], and an increased risk of infective endocarditis [24]. The cumulative impact of these complications emphasizes the need for timely identification and appropriate management to prevent long-term morbidity. Once a PDL is diagnosed, the question is whether it should be monitored with frequent imaging observation, long-term anticoagulation, or prophylactic PDL closure. The selection of a management strategy is made more complex by the temporal regression of PDL observed in 20% to 40% of patients, particularly in those with leaks <5 mm [67]. Interventional methods for closing larger PDLs involve utilizing vascular plugs, cardiac occluders, detachable coils, radiofrequency ablation, or a combination of these techniques [68,69,70,71]. Additionally, multiple plugs can be placed either simultaneously or in sequence to address larger or crescent-shaped leaks. For very large leaks or entirely uncovered lobes, a second LAA occluder can be utilized following standard LAA occlusion procedures [72].

2.1. WATCHMAN, Amplatzer Amulet, and LARIAT

The WATCHMAN FLX and FLX Pro, developed by Boston Scientific, are two FDA-approved devices for LAA closure. The FLX Pro, an improvement over the original FLX, incorporates three significant enhancements: a thromboresistant coating to aid in healing, radiopaque markers for improved visibility during surgery, and an option for a larger size to accommodate a broader range of patients [73]. The Amplatzer Amulet by Abbott is another FDA-approved device with two components: a lobe ranging between 7.5–10 mm and a disk with a size range of 22–41 mm. The design of the lobe is intended to provide enhanced sealing of the LAA compared to the WATCHMAN FLX. In contrast to these permanent implant devices, the FDA-approved LARIAT Suture Delivery Device offers a minimally invasive approach, utilizing a catheter to deliver a synching suture loop around the exterior of the LAA. This process is guided by a second catheter with a magnetic tip from inside the LAA [74,75]. However, the LARIAT device requires two access points, increasing the procedural complexity [76]. One access site is through the groin, similar to other devices, while the second site requires a needle insertion through the chest wall and pericardial sac. Factors such as a large LAA size, specific LAA orientations, or scar tissue from prior surgeries may limit the device’s applicability. Additionally, the LARIAT procedure carries the risk of incomplete sealing of the LAA. Due to these complexities, the LARIAT procedure is generally considered more intricate than other LAA closure devices.

The landmark Amplatzer Amulet IDE trial [77], representing the largest randomized LAA occlusion clinical trial comparing two devices head-to-head, demonstrated sustained long-term benefits through 5 years of follow-up. The trial showed that significantly more patients with the Amulet occluder were free from OAC compared to the WATCHMAN device (94.0% vs. 90.9%, p = 0.009) at 5 years. Both devices showed similar rates of key clinical outcomes, including the composite of ischemic stroke or systemic embolism (7.4% vs. 7.1%, p = 0.851), composite of stroke/systemic embolism/cardiovascular death (20.3% vs. 20.7%, p = 0.666), major bleeding (20% vs. 20.0%, p = 0.882), cardiovascular death (14.3% vs. 15.4%, p = 0.429), and all-cause death (28.7% vs. 31.1%, p = 0.217). Notably, both devices achieved low annualized ischemic stroke rates of 1.6%/year, representing approximately 78–79% reduction from predicted rates based on CHA₂DS₂-VASc scores. However, the Amulet occluder demonstrated an important safety advantage, with significantly fewer fatal or disabling strokes (22 vs. 39 events, p = 0.030) than the WATCHMAN device. Additionally, device-related factors (device-related thrombus or PDL ≥ 3mm) preceded stroke events and cardiovascular deaths less frequently with the Amulet occluder compared to the WATCHMAN device (31 vs. 63 events), suggesting better long-term device performance and safety profile with the dual-seal technology.

Table 2. Comparison of FDA-approved LAA occluder devices.

Device Image	Device Name	Manufacturer	Key Features	Challenges/Limitations
(Photo courtesy Boston Scientific)	WATCHMAN FLX and FLX Pro [78]	Boston Scientific	Thromboresistant coating; radiopaque markers; larger size option (FLX Pro).	PDL; risk of device-related thrombus.
(Photo courtesy Abbott)	Amplatzer Amulet [78]	Abbott	Lobe (7.5–10 mm); Disk (22–41 mm); enhanced LAA sealing.	PDL, device size, and fit.
(Photo courtesy SentreHEART)	LARIAT suture delivery	SentreHEART	Minimally invasive; suture loop around LAA; guided by magnetic catheter.	Two access points; large LAA size; specific orientations; scar tissue; risk of incomplete sealing.

provides a comparison of FDA-approved LAA occluder devices.

Evidence for PDL reduction with newer generations of these devices has been demonstrated in several studies. The PINNACLE FLX trial showed that the WATCHMAN FLX device achieved a significantly lower PDL rate of 17.4% at 45 days compared to the 40.9% seen with the first-generation device in PROTECT AF [64]. This improvement is attributable to the device’s enhanced conformability and wider range of sizes. Similarly, the Amulet IDE trial demonstrated that the dual-seal technology of the Amplatzer Amulet resulted in fewer significant PDLs (≥3mm) at 12 months (9.5%) compared to the WATCHMAN device (21.7%) [65]. The long-term durability of these improvements was confirmed in 5-year follow-up data showing sustained PDL reduction [77].

2.2. CLAAS System

Several devices are currently developing at various stages, to address the limitations of existing FDA-approved LAA occlusion devices (Table 3). One notable example is the CLAAS System by Conformal Medical, Inc., designed to improve the device to the LAA and reduce PDLs [79,80,81]. The CLAAS device incorporates a novel polyurethane–polycarbonate urea foam matrix surrounding a nitinol endoskeleton to enhance sealing and promote tissue ingrowth. This passive foam-based design allows the implant to expand in width during compression, potentially enabling more effective sealing of oval-shaped LAA ostia and accommodating a more comprehensive range of LAA anatomies with just two device sizes [79]. Preclinical studies in canine models have demonstrated promising results for the CLAAS device. A 150-day study showed complete LAA sealing, appropriate healing responses, and no signs of systemic embolization, infection, or toxicity [81]. The foam matrix was observed to fold at the distal edge, providing an atraumatic surface to minimize the risk of LAA damage.

Additionally, a first-in-human study using ICE guidance for CLAAS implantation demonstrated feasibility and encouraging 1-year clinical outcomes [80]. The study reported 100% procedural success, with no significant procedure-related complications and only one instance of device-related thrombus at six months post-implantation. While the CLAAS System shows promise in addressing some limitations of current LAA occlusion devices, challenges remain. Although the foam layer improves conformity, the device’s core frame is still circular, which may not perfectly match highly irregular LAA geometries in all cases. Furthermore, the availability of only two sizes (regular and large) may limit its applicability to the full spectrum of LAA anatomies encountered in clinical practice [79]. To further evaluate the safety and efficacy of the CLAAS device, a large RCT comparing it to the WATCHMAN FLX device is planned to commence [80]. Additionally, a current clinical trial (NCT05147792) is assessing the safety and effectiveness of the CLAAS System in patients experiencing non-valvular AF who are at higher risk of ischemic stroke. The trial aims to enroll approximately 1600 participants, with primary completion expected in December 2026. The evidence for PDL prevention with the CLAAS System comes from preclinical and early clinical studies. In a 150-day canine study, the device achieved complete LAA sealing in all cases (n = 8), with no evidence of PDL on follow-up imaging [81]. The foam-based design showed superior conformability to irregular anatomies, with CT imaging confirming complete seal maintenance throughout the study period. First-in-human results (n = 30) demonstrated 97% freedom from significant PDL at 12 months [80], suggesting potential advantages over conventional rigid-frame devices.

2.3. Occlutech

Next is the Occlutech LAA occluder, which obtained European CE mark approval and consists of a self-expanding nitinol wire mesh with a conical shape that adapts to the LAA anatomy. The device features distally attached loops and additional anchoring elements on its flank, to secure positioning within the LAA. Its outer surface is partially covered by a modified, non-woven, biostable polyurethane layer that aids in sealing the LAA ostium. The Occlutech LAA occluder is delivered via a steerable guiding sheath, allowing 180-degree rotation to access challenging LAA anatomies. While the Occlutech LAA device shows promise, it does have some limitations. In preclinical studies, device protrusion into the left atrium was observed in about 33% of cases, though most were minor (2–3 mm). In some animals, the distal loops used for anchoring penetrated the distal LAA lobe, although this did not lead to significant complications. The device requires oversizing by 3–4 mm, at the high end of the initially recommended range, potentially limiting its use in specific LAA anatomies. Like other LAA closure devices, a learning curve is associated with proper sizing and deployment. The long-term durability and efficacy of the device in humans and its performance compared to other established LAA occluders remain to be thoroughly evaluated in clinical trials [82,83]. Initial evidence for the Occlutech device’s effectiveness in preventing PDL comes from a porcine model study (n = 12) showing complete LAA sealing in 92% of cases at 90 days [82]. The conical shape and additional anchoring elements demonstrated superior adaptation to various LAA morphologies. First-in-human experience (n = 30) reported a PDL rate of 10% at 45 days [83], though larger randomized trials are needed to confirm these preliminary findings.

2.4. LAmbre

The LAmbre device from LifeTech Scientific consists of a self-expanding nitinol mesh structure with a unique double-disc design which has an umbrella-shaped disc that anchors inside the LAA and a cover disc that seals the LAA ostium. The umbrella contains eight distal hooks for engagement with the LAA wall and eight U-shaped ends to trap LAA trabeculations, providing a double stabilization mechanism. This design allows the LAmbre to adapt to various LAA morphologies, including challenging anatomies like chicken-wing and multi-lobe LAAs. The device is available in multiple sizes, to accommodate LAA ostia up to 40 mm in diameter. It is delivered through a smaller 10.4–12.3 Fr sheath than other LAA occlusion devices, potentially reducing access site complications. Studies have shown high implant success rates and good short-term safety profiles for the LAmbre device, comparable to more established devices like the WATCHMAN and Amulet. However, the LAmbre device also has some limitations. As a relatively new device, long-term data on its efficacy for stroke prevention and safety still need to be assessed compared to more established LAA occluders.

While the double-disc design provides good stability, proper alignment of the cover disc with the LAA ostium can be challenging in some anatomies, potentially leading to incomplete sealing or the need for repositioning. The studies reviewed noted cases where device misalignments resulted in significant PDLs, requiring additional interventions. Additionally, like other LAA occlusion devices, a learning curve is associated with proper sizing and deployment techniques. Further research and longer-term follow-up studies are needed, to fully elucidate the performance and potential limitations of the LAmbre device in diverse patient populations and LAA anatomies [84,85,86]. The LAmbre device’s effectiveness in preventing PDLs is supported by multicenter registry data. In a study of 153 patients, the device achieved a PDL-free rate of 95% at 12 months [84]. The unique double-disc design with U-shaped ends demonstrated particular effectiveness in challenging anatomies, with a technical success rate of 99.4%. However, the registry noted that proper disc alignment remains crucial for preventing PDLs, with a learning curve effect observed in initial cases [85].

2.5. Appligator

Unlike traditional metal-based implants, the Appligator from Append Medical uses a suction mechanism to invert the LAA. It applies a suture loop inside the left atrium, relying on the LAA’s natural tendency to shrink over time after constriction. This innovative method addresses common issues with current LAA closure techniques, particularly the risk of leaks. The Appligator’s metal-free approach may also be more cost-effective. The ongoing clinical investigation aims to provide clinical proof-of-concept results. Despite its potential advantages, its long-term efficacy in stroke prevention, its ability to accommodate various LAA morphologies, and the risk of thrombosis due to altered hemodynamics remain to be determined. The procedure’s safety, particularly regarding the risk of tissue rupture during LAA inversion, needs more detailed and longer-term evaluation. Additionally, the learning curve for physicians, optimal patient selection criteria, and direct comparisons with existing LAA closure methods must be addressed. As the Appligator progresses through clinical trials and regulatory processes, these factors will be crucial in determining its ultimate effectiveness in LAA closure. While the Appligator’s novel suction mechanism shows promise for complete LAA closure, current evidence is limited to bench testing and animal studies. Initial acute studies in porcine models (n = 10) demonstrated complete LAA exclusion without PDL in 90% of cases, though long-term data are pending. The ongoing first-in-human trial (NCT05147792) will provide crucial evidence regarding its effectiveness in preventing PDL compared to conventional devices.

2.6. Cormos

The Cormos Medical LAA Occluder offers a unique approach to LAA closure, with its versatile design and advanced features. The Cormos LAA Occluder comes in two versions: Type I with a proximal disc and Type II without a disc, both available in various sizes to accommodate different LAA morphologies. This system’s flexibility is potentially advantageous, allowing physicians to select the appropriate occluder type during the catheterization procedure using the Cormos Medical steerable introducer. One of the standout features of the Cormos LAA Occluder is its anchoring system, which utilizes between 15 and 21 J-hooks for optimal coverage and secure placement within the LAA. The device’s double membrane system allows for flexible adaptation to different LAA depths, while the electropolished surfaces reduce frictional forces during deployment and minimize the risk of thrombus formation. The four-phase discharge process, including a phase with retracted hooks, enables improved positioning and intermediate checks before final anchoring. Additionally, the occluder is retrievable at all implantation phases, enhancing safety and control during the procedure.

2.7. Ultraseal

The Ultraseal (Cardia, Eagan, Minnesota) LAA has a self-expandable nitinol device with a distal lobe for anchoring within the LAA, a proximal disc for sealing the LAA ostium, and an articulating waist connecting the two components [87,88]. Available in 10 sizes ranging from 16 to 34 mm, with lengths between 10 and 18 mm, the Ultraseal offers improved flexibility and adaptability to complex LAA anatomies, due to its reduced radial force and more flexible central waist [89]. The device’s compact design allows for a recommended 10–20% oversizing between the lobe and the landing zone, though real-world data suggests successful implantation has been achieved with oversizing up to 29 ± 20% [89]. Clinical experience across multiple studies has demonstrated promising performance with the second-generation device. Early single-center experiences [88] and subsequent larger registries [87,89] have shown successful implantation across diverse LAA morphologies, including challenging chicken-wing anatomies. Initial concerns about device fracture with the first generation [90] have been addressed through design modifications, as evidenced by the absence of fractures in recent registry data [89]. Procedural success rates have consistently ranged between 94.2–100%, with a notably low in-hospital complication rate of 5.8% reported in multicenter experience. Long-term device performance and post-procedural management remain key considerations in clinical practice. The incidence of significant residual leaks (>5 mm) appears low with the second-generation device, reported between 1.9–2.9% in recent studies [89]. Device-related thrombosis rates have varied from 0–8.3% across different cohorts, highlighting the importance of optimized post-procedural antithrombotic strategies. While early results are promising, with trans-esophageal echocardiography at median 61-day follow-up showing favorable outcomes, the current evidence base is limited by relatively small sample sizes and short follow-up periods. More extensive trials with longer-term follow-up are warranted, to fully evaluate the device’s performance, particularly in comparison to other established LAA occluder devices.

2.8. Omega

The Omega LAA occluder by Eclipse Medical features a self-expanding nitinol mesh structure coated with platinum, including a distal cup and proximal disc connected by a flexible waist. Key design elements include anchoring hooks on the cup for stability, a polypropylene fabric inside the disc for enhanced occlusion, and sizes ranging from 14 to 30 mm. The device’s highly flexible connecting waist allows it to adapt to complex LAA morphologies, including sharply angulated appendages [76,91,92]. This design potentially enables the Omega device to treat a broader range of LAA anatomies compared to some existing devices. The smallest 14 mm size is unique in the market, allowing the treatment of LAAs with landing zones as small as 10 mm. However, using multiple components, including the nitinol mesh, platinum coating, polypropylene fabric, and polyester stitching, increases the complexity of the device. This complexity could impact long-term durability or increase the risk of component failure. The flexible waist, while advantageous for conforming to various LAA shapes, might also allow for more movement of the device within the LAA, potentially affecting long-term stability or seal. Also, fabric-covered discs for LAA sealing rely on endothelialization for complete closure. This process can vary between patients and may not be as immediate as other sealing mechanisms.

2.9. Laminar

The Laminar LAA Exclusion System represents an innovative approach to LAA closure that utilizes a fundamentally different mechanism compared to traditional occluder devices [93]. Rather than employing a plug-based design, the Laminar system uses a novel rotational closure mechanism to exclude the LAA, potentially addressing some key limitations of current devices regarding PDL formation. The device consists of two integrated components: a self-expanding nitinol ball structure and a flower-shaped lock with six petals. The atraumatic ball expands to engage the LAA tissue without hooks or barbs, while the lock is designed to compress and seal the tissue. This design achieves LAA closure through tissue rotation and compression rather than occlusion, effectively eliminating the residual LAA pouch. A notable feature of the Laminar system is its minimal surface area exposure to the left atrium, which is less than 5% compared to conventional devices like the 27 mm Watchman FLX or 28 mm Amulet. This reduced profile may lower the risk of device-related thrombosis formation [93]. The system utilizes an 18-F double-curve steerable guide with 0° to 90° primary flexion capability, allowing precise positioning during deployment.

Early clinical evidence has demonstrated promising results. In a first-in-human study of 15 patients, the device achieved 100% procedural success with no safety events through 12 months of follow-up. Complete closure (no leak > 5 mm) was achieved in all patients, with only two cases showing minimal tissue pleats <3 mm without communication into the LAA. The system accommodated various LAA morphologies and demonstrated stable positioning on follow-up imaging. Currently, a pivotal IDE study is underway to evaluate the system’s safety and efficacy compared to commercially available LAA closure devices. The trial aims to enroll 1500 patients across up to 100 U.S. sites. This study will provide important insights into the potential advantages of this novel closure mechanism in addressing PDL-related challenges. The Laminar system exemplifies an innovative direction in LAA closure technology, potentially offering advantages through its unique rotational closure mechanism and minimal surface area design. However, longer-term data from larger patient populations will be necessary to fully understand its clinical impact and role in PDL prevention.

Table 3. Comparison of LAA occluder devices currently being investigated.

Device Image	Name, Manufacturer	Key Features	Challenges/Limitations
(Photo courtesy Conformal Medical)	CLAAS [81] Conformal Medical	PCUU foam matrix surrounding nitinol endoskeleton; enhanced conformity; atraumatic surface, due to foam folding at distal edge.	Limited to two sizes; may not cover full spectrum of LAA anatomies; long-term efficacy and safety data still being collected.
(Photo courtesy Occlutech International)	LAA Oclutech [82] Occlutech International	Self-expanding nitinol wire mesh with conical shape; distally attached loops and additional anchoring elements on flank; delivered via steerable guiding sheath allowing 180-degree rotation.	Distal loops penetrated LAA lobe in some animals; requires oversizing by 3–4 mm; learning curve for proper sizing and deployment.
(Photo courtesy LifeTech Scientific)	LAmbre LifeTech Scientific	Double-disc design with umbrella-shaped anchoring disc and cover disc; eight distal hooks and eight U-shaped ends; multiple sizes for LAA up to 40 mm, smaller delivery sheath (10.4–12.3 Fr).	Cases of device misalignment leading to significant PDL and minor PDL not uncommon.
(Photo courtesy Append Medical)	Appligator Append Medical	Uses suction mechanism to invert LAA; applies suture loop from inside left atrium; metal-free approach; capitalizes on LAA’s natural tendency to shrink.	Risk of thrombosis due to altered hemodynamics; potential risk of tissue rupture during LAA inversion; optimal patient selection criteria not established.
(Photo courtesy Cormos Medical)	Cormos Occluder Cormos Medical	Double membrane system for flexible adaptation; between 15 and 21 J-hooks for anchoring, electropolished surfaces; retrievable at all implantation phases.	Potential learning curve for new deployment technique; long-term durability and efficacy need further evaluation.
(Photo courtesy Cardia)	Ultraseal [89] Cardia	Flexible design with reduced radial force, allowing adaptation to complex LAA; compact structure with lengths between 10 and 18 mm, available in 10 sizes (16–34 mm).	Limited long-term data available, due to small sample sizes and short follow-up periods; optimal post-procedural antithrombotic regimen not yet established.
(Photo courtesy Eclipse Medical)	Omega [94] Eclipse Medical	Self-expanding nitinol mesh structure with platinum coating; highly flexible connecting waist to adapt to complex LAA morphologies; available in sizes from 14 to 30 mm, including a unique 14 mm size for small landing zones.	Complex design with multiple components may impact long-term durability; flexible waist could potentially allow more device movement within the LAA; fabric-covered disc relies on variable endothelialization process.
(Photo courtesy Biosense Webster)	Laminar LAAX System [93] Biosense Webster, Inc.	Rotational closure mechanism with integrated ball and lock design; self-expanding nitinol ball structure for LAA tissue engagement; no hooks or barbs required for anchoring, minimal LA-facing surface area; 18-F double-curve steerable guide system; two device sizes (12 mm and 16 mm).	Long-term durability data still being collected; currently in pivotal trial phase; learning curve for novel rotational closure technique; limited real-world experience outside clinical trials; optimal patient selection criteria still being established.

Table 3. Comparison of LAA occluder devices currently being investigated.

Device Image	Name, Manufacturer	Key Features	Challenges/Limitations
(Photo courtesy Conformal Medical)	CLAAS [81] Conformal Medical	PCUU foam matrix surrounding nitinol endoskeleton; enhanced conformity; atraumatic surface, due to foam folding at distal edge.	Limited to two sizes; may not cover full spectrum of LAA anatomies; long-term efficacy and safety data still being collected.
(Photo courtesy Occlutech International)	LAA Oclutech [82] Occlutech International	Self-expanding nitinol wire mesh with conical shape; distally attached loops and additional anchoring elements on flank; delivered via steerable guiding sheath allowing 180-degree rotation.	Distal loops penetrated LAA lobe in some animals; requires oversizing by 3–4 mm; learning curve for proper sizing and deployment.
(Photo courtesy LifeTech Scientific)	LAmbre LifeTech Scientific	Double-disc design with umbrella-shaped anchoring disc and cover disc; eight distal hooks and eight U-shaped ends; multiple sizes for LAA up to 40 mm, smaller delivery sheath (10.4–12.3 Fr).	Cases of device misalignment leading to significant PDL and minor PDL not uncommon.
(Photo courtesy Append Medical)	Appligator Append Medical	Uses suction mechanism to invert LAA; applies suture loop from inside left atrium; metal-free approach; capitalizes on LAA’s natural tendency to shrink.	Risk of thrombosis due to altered hemodynamics; potential risk of tissue rupture during LAA inversion; optimal patient selection criteria not established.
(Photo courtesy Cormos Medical)	Cormos Occluder Cormos Medical	Double membrane system for flexible adaptation; between 15 and 21 J-hooks for anchoring, electropolished surfaces; retrievable at all implantation phases.	Potential learning curve for new deployment technique; long-term durability and efficacy need further evaluation.
(Photo courtesy Cardia)	Ultraseal [89] Cardia	Flexible design with reduced radial force, allowing adaptation to complex LAA; compact structure with lengths between 10 and 18 mm, available in 10 sizes (16–34 mm).	Limited long-term data available, due to small sample sizes and short follow-up periods; optimal post-procedural antithrombotic regimen not yet established.
(Photo courtesy Eclipse Medical)	Omega [94] Eclipse Medical	Self-expanding nitinol mesh structure with platinum coating; highly flexible connecting waist to adapt to complex LAA morphologies; available in sizes from 14 to 30 mm, including a unique 14 mm size for small landing zones.	Complex design with multiple components may impact long-term durability; flexible waist could potentially allow more device movement within the LAA; fabric-covered disc relies on variable endothelialization process.
(Photo courtesy Biosense Webster)	Laminar LAAX System [93] Biosense Webster, Inc.	Rotational closure mechanism with integrated ball and lock design; self-expanding nitinol ball structure for LAA tissue engagement; no hooks or barbs required for anchoring, minimal LA-facing surface area; 18-F double-curve steerable guide system; two device sizes (12 mm and 16 mm).	Long-term durability data still being collected; currently in pivotal trial phase; learning curve for novel rotational closure technique; limited real-world experience outside clinical trials; optimal patient selection criteria still being established.

3. Discussion

Current LAA occluder technologies, while promising, face significant challenges in achieving optimal outcomes for all patients. The intricate relationship between PDLs and device embolization represents a critical consideration in LAA occlusion procedures. Device embolization represents a rare but potentially catastrophic complication that shares mechanistic links with PDLs. Clinical evidence suggests that the presence of a PDL may serve as an early indicator of suboptimal device positioning or anchoring, potentially increasing the risk of subsequent device embolization. The mechanisms connecting these complications typically involve anatomical challenges, including unfavorable LAA morphology, incorrect device sizing, or insufficient device engagement with the LAA wall. When a PDL is detected, it may indicate inadequate compression of the device against the LAA wall, which not only allows for blood flow around the device but also suggests insufficient anchoring force. This mechanical relationship underscores the importance of proper initial device sizing and positioning, as well as the need for careful assessment of both complications during follow-up imaging. Studies have demonstrated that up to 31% of device embolization cases are preceded by a detectable PDL, highlighting the potential value of PDLs as warning signs for impending device instability.

A critical issue that has emerged in recent years is the occurrence of PDLs, which can significantly impact the efficacy of LAA occlusion. The meta-analysis of the WATCHMAN trials (PROTECT-AF and PREVAIL) and their continued access registries highlighted the complex balance between procedural risks and long-term benefits [95]. While LAA closure showed reductions in hemorrhagic stroke and cardiovascular death compared to OACs, the inclusion of peri-procedural complications negated these advantages, emphasizing the critical need for improved device designs and deployment techniques. PDLs have emerged as a crucial concern in LAA occlusion procedures, with significant implications for patient outcomes. Alkhouli et al. highlighted that PDLs affect a substantial proportion of patients undergoing LAA occlusion, potentially undermining the procedure’s effectiveness in preventing thrombo-embolism [96]. This challenge underscores the limitations of current devices with circular cross-sections in adapting to the complex and variable geometry of the LAA across patients, emphasizing the need for more adaptable and patient-specific solutions.

The incidence of device-associated complications further complicates the landscape of LAA occlusion. A systematic review reported a 3.9% rate of device-associated thrombus formation [97], while the PROTECT-AF trial data revealed additional concerns, including device embolization (0.6%), air embolization (0.6%), peri-procedural stroke (0.9%), and pericardial severe effusion (4.8%) [98]. These complications, often related to incomplete sealing and PDLs, highlight the critical importance of achieving a perfect fit between the device and the LAA anatomy to minimize risks and optimize outcomes. Targeted imaging of the thrombosis to evaluate device-related thrombosis would facilitate understanding of the link between thrombosis and the leak. Several positron emission tomography (PET)-labeled probes have been developed for imaging thrombosis, including ⁶⁴Cu-FBP8, which targets fibrin, and ¹⁸F-GP1, which targets the glycoprotein IIb/IIa receptors on activated platelets [99,100]

The variability in LAA anatomy presents a significant hurdle for current circular devices, contributing to the challenge of preventing PDLs. With LAA volumes ranging from 0.77 to 19.27 cm³ [101] and shapes classified into six distinct types [102], standard devices struggle to achieve complete sealing in all patients. This anatomical diversity limits the universal applicability of current devices and increases the risk of incomplete sealing, potentially promoting clot formation within the appendage and elevating the risk of device embolization and PDLs. Recent studies have also shed light on the impact of LAA occlusion on left atrial hemodynamics, adding another layer of complexity to device design considerations. Bshennaty et al. [103] demonstrated that LAA exclusion alters flow dynamics within the left atrium, potentially affecting the risk of thrombus formation. Their findings suggest that the ideal device design should focus on achieving a complete seal to prevent PDLs and consider its impact on overall left atrial flow patterns, to minimize the risk of thrombus formation in other areas of the atrium. Given these challenges, there is a pressing need for innovation in LAA occluder design, which is summarized in Table 4.

3.1. Surface Modification

One option to reduce PDLs is to apply advanced surface modification techniques in combination with optimized 3D structures. A recent study has demonstrated the potential of this approach by developing a novel LAA occluder that integrates a 2D nanocoating surface modification with an innovative 3D structural design [104]. The researchers developed a surface modification technique for nickel–titanium (NiTi) alloy, applying alternating nanoscale layers of titanium and titanium nitride (TiN), which demonstrated significant enhancement of endothelial cell migration in vitro and accelerated endothelialization in vivo, potentially reducing the risk of thrombosis and improving device sealing. Concurrently, they engineered a flexible 3D structure incorporating a double stabilization system with hooks and U-shaped anchors, enabling secure fixation while maintaining retrievability. However, there is a need for long-term studies on the effects of nanocoating in humans, the limited clinical evidence presented, and the need for direct head-to-head comparisons with existing devices in clinical settings. More extensive clinical trials with larger patient cohorts and extended follow-up periods are necessary, to establish the superiority and long-term safety profile of this novel LAA occluder.

3.2. Upconversion 3D Bioprinting

Bioprinting the LAA presents another innovative approach to reducing PDL potentially [105]. This method involves creating a patient-specific, 3D-printed biological structure that closely mimics the patient’s unique LAA anatomy, using the patient’s cells or biocompatible materials to create a custom-fit “plug” that more effectively seals the LAA. This personalized approach may address the variations in LAA morphology that often contribute to incomplete closure and subsequent leaks with current occlusion devices. The printed LAA implant can significantly improve long-term outcomes by promoting tissue integration and endothelialization, potentially enhancing the seal’s durability. By incorporating growth factors or other bioactive molecules into the printed structure, the implant could encourage natural tissue healing and remodeling around the occlusion site. Supporting this idea, recent research has demonstrated a novel upconversion nanoparticle (UCNP)-assisted 3D-bioprinting approach for non-invasive in vivo molding [106]. This method uses UCNPs that convert near-infrared (NIR) photons into blue–violet emission, to induce polymerization of biocompatible hydrogels in vivo. Using a fused deposition modeling coordination framework, researchers were able to precisely control the movement of am NIR laser to fabricate implantable medical devices with tailored shapes, successfully demonstrating the 3D bioprinting of a non-invasive fracture fixation scaffold and showcasing the potential for in vivo fabrication of medical implants without invasive surgery. While this bioprinting approach shows promise for reducing PDLs in LAA occlusion, some limitations must be considered. The long-term safety and efficacy of in vivo bioprinted structures in the cardiac environment needs thorough evaluation, with concerns about the stability of the bioprinted material over time and its interaction with blood flow and cardiac tissue. Additionally, the precision and resolution of in vivo bioprinting in the complex, moving environment of the heart would need significant improvement, to ensure accurate and complete LAA occlusion. Finally, the regulatory pathway for such a novel approach would likely be complex and time-consuming, potentially delaying clinical implementation.

3.3. Patient-Specific Occluder

Patient-specific (PS) occluder devices customized to individual LAA anatomies represent a promising avenue for improving outcomes and reducing the incidence of PDLs. PS occluders are a novel approach to LAA closure that aims to address the limitations of conventional one-shape-fits-all devices [107,108,109]. By precisely matching the complex geometry of each patient’s LAA, such devices can achieve complete sealing, significantly reduce the risk of PDLs, and they can minimize alterations to left atrial hemodynamics. The key feature of these devices is their customized geometry, which is designed to match the unique anatomy of each patient’s LAA precisely. This customization is achieved through pre-operative CT image segmentation, 3D modeling, and advanced manufacturing techniques like 3D printing and molding of soft materials. The PS occluders are fabricated as thin-walled, inflatable balloons made from soft, biocompatible materials such as elastomeric polyurethanes [108]. This design allows the device to be compressed for minimally invasive catheter delivery and inflated to conform to the LAA’s complex internal geometry. A notable feature is the incorporation of biomimetic surface patterns inspired by tree frog toe pads, which enhance wet adhesion and improve anchoring without hooks or barbs [109]. The advantages of PS occluders, as demonstrated through in vitro testing, include superior anchoring force, significantly reduced leak rates, and less protrusion into the left atrium compared to conventional designs [109]. The personalized shape allows for more evenly distributed contact with the LAA walls, potentially reducing the risk of tissue damage or perforation. These devices’ soft, compliant nature enables them to adapt to any irregularities or features not captured in the initial imaging, potentially providing a more complete occlusion. However, the manufacturing process of PS LAA occluders represents a significantly more complex manufacturing and regulatory approval pathway, since the process of creating and fabricating each device must be shown to be consistent and effective for all patients [107]. Ensuring consistent quality and mechanical properties across custom-made devices is a new frontier in medical devices. In addition, these inflated soft material balloon-like occluders must be evaluated for long-term durability and stability. Another aspect is that the delivery of these devices must be done in a particular orientation, which is more complicated than conventional circular-shaped occluders. Most importantly, although the in vitro and initial in vivo results are encouraging, thorough clinical trials will be essential, to confirm the safety and effectiveness of PS occluders in humans before they can be approved for clinical application [109].

3.4. Shape Memory Biodegradable

The study by Xiang et al. presents an innovative approach to developing biodegradable occluders using a poly/gold nanorod composite [110]. This material combines shape memory properties with NIR light-triggered deployment, offering a remotely controllable and fully biodegradable solution. The occluder’s skeleton is made of PLCL-GNR/PEG, which can be compressed for catheter delivery and then expanded at the defect site, using NIR light stimulation. This approach addresses several key challenges in current occluder designs, including the need for biodegradability to eliminate long-term foreign body responses and the desire for precise, controlled deployment. The main advantages of this approach include its biodegradability, which eliminates complications associated with permanent implants, and the ability to control the deployment process using NIR light spatiotemporally. However, the limitations of this method include the potential long-term effects of gold nanoparticles in the body, which may require further investigation. Additionally, NIR light stimulation may complicate the deployment procedure in clinical settings, potentially requiring specialized equipment or training. The study also focused primarily on in vitro and ex vivo testing. Further in vivo studies and clinical trials would be necessary, to fully validate the safety and efficacy of this approach in human patients.

Table 4. Comparison of new innovations in LAA occluder devices currently being investigated.

Device Image	Device/Method	Key Features	Challenges/Limitations
	surface modification [104]	Advanced surface modification, using alternating nanoscale layers of TiN on NiTi alloy, enhancing endothelial cell migration and accelerating endothelialization; successful clinical implantation.	Lack of long-term studies on the effects and potential complications of the nanocoating in humans; limited clinical evidence, with only one reported case.
	upconversion 3D bioprinting [106]	Patient-specific 3D-printed implants; enhanced tissue integration; in vivo non-invasive fabrication.	Long-term concerns; precision challenges for bioprinting in cardiac environment; complex regulatory pathway.
	patient-specific occluder	Customized geometry for each patient’s LAA; thin-walled, inflatable balloons made from soft, biocompatible materials; incorporates biomimetic surface patterns for enhanced adhesion; superior anchoring force and reduced leak rates in vitro.	Complex manufacturing process; challenges in ensuring consistent quality across custom devices; long-term durability of soft materials needs evaluation; potentially higher cost, due to customization.
	shape memory biodegradable [110]	NIR light-triggered shape memory effect for controlled deployment; fully biodegradable composition, using PLCL-GNR/PEG composite; maintained mechanical strength during initial tissue regeneration phase.	Long-term effects of gold nanoparticles require further study; NIR light stimulation may complicate clinical deployment procedures; primarily tested in vitro/ex vivo; needs further in vivo validation.
	bio-inspired absorbable [111]	Bio-inspired design with wavy microstructures mimicking collagen fibrils, exhibiting “J-shaped” stress–strain behavior; 4D printing enabling patient-specific geometries and shape transformation.	Need for optimization of shape memory transition temperature; preliminary nature of in vitro feasibility testing.

Table 4. Comparison of new innovations in LAA occluder devices currently being investigated.

Device Image	Device/Method	Key Features	Challenges/Limitations
	surface modification [104]	Advanced surface modification, using alternating nanoscale layers of TiN on NiTi alloy, enhancing endothelial cell migration and accelerating endothelialization; successful clinical implantation.	Lack of long-term studies on the effects and potential complications of the nanocoating in humans; limited clinical evidence, with only one reported case.
	upconversion 3D bioprinting [106]	Patient-specific 3D-printed implants; enhanced tissue integration; in vivo non-invasive fabrication.	Long-term concerns; precision challenges for bioprinting in cardiac environment; complex regulatory pathway.
	patient-specific occluder	Customized geometry for each patient’s LAA; thin-walled, inflatable balloons made from soft, biocompatible materials; incorporates biomimetic surface patterns for enhanced adhesion; superior anchoring force and reduced leak rates in vitro.	Complex manufacturing process; challenges in ensuring consistent quality across custom devices; long-term durability of soft materials needs evaluation; potentially higher cost, due to customization.
	shape memory biodegradable [110]	NIR light-triggered shape memory effect for controlled deployment; fully biodegradable composition, using PLCL-GNR/PEG composite; maintained mechanical strength during initial tissue regeneration phase.	Long-term effects of gold nanoparticles require further study; NIR light stimulation may complicate clinical deployment procedures; primarily tested in vitro/ex vivo; needs further in vivo validation.
	bio-inspired absorbable [111]	Bio-inspired design with wavy microstructures mimicking collagen fibrils, exhibiting “J-shaped” stress–strain behavior; 4D printing enabling patient-specific geometries and shape transformation.	Need for optimization of shape memory transition temperature; preliminary nature of in vitro feasibility testing.

3.5. Bio-Inspired Absorbable

Another method for addressing PDL in LAA occlusion devices involves the development of 4D-printed bio-inspired, biodegradable structures. This approach, introduced by Lin et al., uses shape memory polylactic acid (PLA) composites with magnetic nanoparticles to create customizable occluders [111]. These devices have wavy microstructures inspired by collagen fibrils, aiming to mimic the mechanical properties of biological tissues. This design allows the occluders to exhibit nonlinear “J-shaped” stress–strain behavior similar to natural tissues, potentially reducing the risk of tissue damage and improving overall compatibility. The 4D printing enables the fabrication of patient-specific geometries, while the biodegradable nature of the materials may mitigate long-term complications associated with permanent implants. Key features of this method include the ability to transform from a compact temporary shape to an expanded functional form when triggered by heat or a magnetic field, facilitating minimally invasive deployment. Single-layer and double-layer LAA occlusion designs were developed and tested comprehensively, including mechanical assessments, degradation analyses, and biocompatibility evaluations. The occluders demonstrated promising durability in cyclic compression tests and favorable biocompatibility in 48-week implantation studies. However, limitations of this approach include the need for further optimization of the shape memory transition temperature and the preliminary nature of the in vitro feasibility testing.

The clinical implementation of emerging technologies, while holding great promise for enhancing LAA occlusion outcomes, faces significant practical challenges. These advanced approaches must navigate complex regulatory pathways, manufacturing scalability issues, and cost constraints that hinder widespread adoption. PS devices require advanced imaging processing, custom manufacturing, and consistent validation across diverse anatomies—factors that extend production timelines and drive up costs compared to standard devices. Similarly, although 3D bioprinting offers unparalleled customization potential, it relies on specialized facilities, expertise, and rigorous quality-control measures that are not universally accessible. Moreover, the regulatory framework for such personalized medical devices is still developing, with authorities working to establish appropriate validation protocols and safety standards. Also, the long-term durability and bio-compatibility of novel materials and technologies in LAA occlusion devices require careful consideration and extensive validation. While emerging approaches like 3D bioprinting, shape memory biodegradable materials, and patient-specific devices show promise, their long-term performance remains uncertain. The biodegradable PLCL-GNR/PEG composites and polyurethane-based materials need a thorough investigation of their degradation profiles, tissue response, and potential for late complications. Critical questions persist about the stability of 3D-printed structures in the dynamic cardiac environment, the tissue integration of novel surface modifications, and the consistency of mechanical properties over time. For bioresorbable devices, the timing and uniformity of degradation must be precisely controlled to maintain effective occlusion while supporting appropriate tissue remodeling. This highlights the need for extended follow-up studies focusing on material integrity, host response, and device performance beyond the typical 1–2-year observation period in current trials. Future research should emphasize accelerated aging studies, comprehensive bio-compatibility testing, and careful monitoring of long-term clinical outcomes to validate these innovative approaches before widespread adoption. In summary, Figure 3 highlights the current challenges, innovative solutions, and future directions for the next generation of LAA occluders to address PDLs.

4. Conclusions

This review highlights that PDLs remain a significant challenge in transcatheter LAA occlusion procedures, with the core issue lying in the inherent variability of LAA anatomy, which limits the effectiveness of current circular occluder devices. Recent research has established a clear association between PDLs and subsequent thrombo-embolic events, emphasizing the need for innovative solutions. To address these challenges, next-generation occluders must be developed with enhanced sealing capabilities and novel closure mechanisms, aiming to better-accommodate the diverse LAA geometries encountered in clinical practice and reduce the incidence of PDLs. Additionally, the development of PS occluders represents a promising avenue for improving outcomes by precisely matching the unique anatomy of each patient’s LAA, potentially achieving complete sealing and minimizing complications. This shift towards personalized LAA occlusion technology could expand the applicability of this treatment to a broader spectrum of patients with atrial fibrillation and represents a new paradigm for cardiovascular implants where device shapes are tailored to individual anatomic morphology. As research in this field progresses, it is crucial to balance the potential benefits of customized devices with practical considerations, such as manufacturing complexity and cost-effectiveness. In conclusion, while the current LAA occluder devices have shown promise in stroke prevention, addressing the challenge of PDLs through innovative designs and PS approaches is essential for improving the long-term efficacy and safety of LAA occlusion procedures, ultimately leading to better outcomes for patients with AF at risk of stroke.