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LAA with implanted AMPLATZER™ AMULET™ cardiac plug in LOVE coronal (a), sagittal (b) and axial (c) view. The colored lines in the pictures indicate their orientation to the plane of the corresponding framing color. Residual flow of contrast agent inside and behind the device in the absence of a PDL represents incomplete neo-endothelialization
Source publication
Purpose:
To bridge neo-endothelialization (NE) of implanted left atrial appendage closure (LAA/LAAC) devices, dual antiplatelet therapy is prescribed. Cardiac computed tomography angiography (cCTA) has been proposed for the evaluation of interventional LAAC. This prospective longitudinal observational study applied a standardized imaging protocol...
Citations
... 17 Both forms of LAA patency, that is, LAA patency with or without visible PDL, were not rare following LAAC device implantation. 12,18,19 The association between PDL and clinical outcomes, especially ischemic stroke, has been observed, but with controversies. The initial results from the PROTECT-AF trial reported the correlations between PDL by TEE and ischemic stroke and cardiovascular death were minimal, 9 which have recently been unveiled by the pooled analyses of PROTECT AF, PREVEIL, and CAP2 studies with extended follow-up periods. ...
BACKGROUND
The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post–LAA closure in patients with atrial fibrillation, remains elusive.
METHODS
Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency.
RESULTS
Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post–LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787–1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17–8.83]; P =0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06–1.17]; P =0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29–10.42]; P =0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71–8.07]; P =0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28–10.09]; P =0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P =0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P =0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P =0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency.
CONCLUSIONS
LAA patency detected by cardiac computed tomography angiography at 3 months post–LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device.
REGISTRATION
URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03788941.
... While this variability might suggest large differences in early endothelialization, the coupling of HAT with endothelial coverage needs additional validation. Visible contrast patency in the distal LAA with or without visible leak has also been suggested as a proxy measure of incomplete endothelial cover, in theory promoting an inverse relationship between low-grade HAT and LAA patency [92,93]. With both LAA patency and HAT being highly variable across studies, further investigation is needed to confirm this correlation and their association with benign healing. ...
Left atrial appendage occlusion (LAAO) is an established alternative to oral anticoagulation for stroke prevention in atrial fibrillation. Antithrombotic therapy is used in the post-procedural period to prevent device-related thrombosis (DRT). The risk of DRT is considered highest in the first 45–90 days after device implantation, based on animal studies of the device healing process. Clinically applied antithrombotic regimens vary greatly across studies, continents, and centers. This article gives an overview of the evidence behind current antithrombotic regimens, ongoing randomized trials, and future post-procedural management.
... There are several methods to detect device endothelializaiton, such as computed tomography and 2-dimentional or 3-dimensional reconstructed TEE. However, these modalities either used indirect evidence, such as dye in LAA without peri-device leak indicating incomplete endothelialization with permeability, 26 or gave poor image qualities, such as using TEE to measure the thickness of possible endothelialization layer, which was usually obscure. By OCT, using near-infrared light, 27 we could clearly see high-resolution images of endothelium and metal struts (just like coronary stent struts). ...
Background
Implantation of the left atrial appendage occluder (LAAO) has been proven to prevent stroke effectively in patients with atrial fibrillation who cannot tolerate anticoagulants. Incomplete endothelization of LAAO may cause device‐related thrombus, and currently no good image modality exists to clearly see LAAO endothelialization. We aimed to use coronary optic coherence tomography (OCT) to visualize LAAO endothelialization.
Methods and Results
We enrolled 14 patients (72.8±9.4 years old) undergoing pulmonary vein isolation with a preexisting LAAO implanted more than 1 year ago (5 Watchman and 9 Amulet). After pulmonary vein isolation, we did OCT via steerable sheath and coronary guiding catheter to adjust OCT probe location and injected contrast medium to visualize the LAAO surface. In vitro testing was also performed to see the bare occluder. In vitro OCT showed the surface of the bare device as an interrupted granule pattern, which included the Watchman surface polytetrafluoroethylene membrane string, Amulet disc metal strut, and inner polytetrafluoroethylene membrane string. In the implanted Watchman, OCT showed endothelialization as a smooth surface layer with noninterrupted coarser granules. In the implanted Amulet, OCT showed endothelialization as thin (early) or thick (late) endothelialization layer covering struts with OCT shadows. Among patients with Watchman, 2 showed no, 2 early, and 1 complete endothelialization. Among patients with Amulet, 2 showed no, 3 early, and 4 late endothelialization.
Conclusions
We demonstrated the feasibility of OCT to visualize LAAO endothelization with high resolution. Further studies are needed to determine antithrombotic regimens if incomplete endothelization is detected. A new OCT catheter may be designed specifically for LAAO.
... In our study, the PDL rate ranged from 10.2% to 68.4%, with 26.2% of patients in the TEE group and 61.7% in the CCTA group having PDLs. The PDL incidence in our study was consistent with that in previous reports [46][47][48]. We also found that the rate of ischaemic stroke/TIA/SE was significantly higher in the group with PDLs detected by TEE, but there was no difference in this rate between the PDL and non-PDL groups diagnosed by CCTA. ...
Background:
Left atrial appendage closure (LAAC) is a safe and effective method for preventing embolic events in patients with nonvalvular atrial fibrillation (NVAF). However, peridevice leaks (PDLs) are sometimes unavoidable. Controversy exists regarding whether PDLs lead to embolic events.
Objectives:
This study aimed to explore the association between PDLs and embolic events, including ischaemic stroke, transient ischaemic attacks (TIA), and systemic embolism (SE).
Methods:
We conducted a systematic search of the PubMed, Web of Science, MEDLINE, and Cochrane Library databases for studies published up to September 25, 2022, to compare the rate of ischaemic stroke/TIA/SE between the PDL group and the non-PDL group after LAAC.
Results:
Thirteen studies comprising 54,405 patients were included in the meta-analysis. The PDL group detected by transoesophageal echocardiography (TEE) had a significantly higher rate of ischaemic stroke/TIA/SE than the non-PDL group (OR: 1.20, 95% CI: 1.08-1.33, P=0.0009). However, no difference in ischaemic stroke/TIA/SE was found between the PDL and non-PDL subgroups of the cardiac computed tomography angiography (CCTA) group (OR: 1.12, 95% CI: 0.51-2.50, P=0.77). CCTA and TEE showed different rates of PDL detection, with the CCTA group having a higher rate of PDL detection (P<0.0001), especially for trivial leaks.
Conclusions:
PDL detected by TEE increases the risk of embolic events after LAAC. However, no association was found between PDL and ischaemic stroke/TIA/SE in the CCTA group, which showed a higher rate of PDL detection than TEE, particularly for trivial leaks. In the future, CCTA may be used to explore the relationship between PDL size and ischaemic stroke/TIA/SE.
... A pilot study showed that neo-endothelialization is still incomplete in a majority of patients at mid-term follow-up of 6 months after successful LAAC therapy. [20] Another study reported that 44 out 84 patients had complete endotheliazation detected with CCTA post LAAC. [21] HCM patients also have high tendency of thrombosis in the left atria when complicated with AF, [15] which might make cease of anticoagulants important risk factors of stroke in this particular subtype of AF patients. ...
Hypertrophic cardiomyopathy (HCM) patients with atrial fibrillation (AF) are at high risk for stroke. Left atrial appendage closure (LAAC) is a promising alternative for stroke prevention in AF patients. We aimed to review the clinical outcomes of patients with AF and HCM at our center. We reviewed 673 patients who underwent LAAC implantation from 2014 to 2021 in a tertiary center, of whom 15 had HCM. AF Patients with HCM were compared with sex and age matched controls who also underwent LAAC. From 2014 to 2021, 673 AF patients received LAAC in a single center, of whom, 15 patients had HCM. LAAC devices were successfully implanted in 14 HCM patients and 59 patients in the control group. During the follow-up period (median 1151 days range: 132-2457 days), 2 HCM patient had ischemic strokes. There were another 2 HCM patients who had sudden cardiac death (SCD). Compared with the control, HCM patients had higher cumulative rate of combined death and stroke (26.67% vs 3.33%, P = .024). In our initial clinical experience, the cumulative stroke and death rate of the HCM patients was significantly higher than that of the non-HCM patients.
... occurred in 14 out of 23 patients (61%) after 10 months of LAAC [32]. Lindner et al. reported an IDE rate of 56% at median follow-up of 6 months post LAAC procedure [33]. Likewise, in another study including 46 patients undergoing successful LAAC, Sivasambu et al. observed that IDE occurred in 28 patients at 45 days during follow-up. ...
... Conversely, Zhao and co-workers reported an IDE rate of 8.3% at 6 months in 84 patients who received successful LAAC and ablation of AF [34]. The explanation for different occurrence rates of IDE after LAAC is multifactorial, and may be, at least partly, related to heterogenous definitions of IDE, various types of LAA occluder, and different cardiac imaging techniques [14,33,35]. ...
... This may partly account for the higher prevalence of IDE in our study. Similar results have been demonstrated by Lindner [33,35], who defined LAA as patent if attenuation of the left atrium exceeded that of the left atrial appendage by 50 HU. ...
Purpose
This study aimed to assess the incidence, potential risk factors and clinical impact of incomplete device endothelialization(IDE) after left atrial appendage closure (LAAC).
Methods
A total of 101 consecutive patients with nonvalvular atrial fibrillation (AF) who underwent successful LAAC and received antithrombotic treatment using a standard regimen were prospectively followed up to 6 months after the procedure. The status of device endothelialization and device-related thrombus (DRT) were evaluated using cardiac computed tomography (CT). Major adverse cardio-cerebral events (MACCE) including all-cause death, heart failure(HF) hospitalization, acute ischemic stroke, transient ischemic attack(TIA), peripheral vascular embolism, and major bleeding were recorded.
Results
IDE was detected in 65 (64.4%) patients. Patients with IDE or complete device endothelialization (CDE) did not significantly differ with respect to baseline clinical characteristics and interventional procedure features. Multivariate analysis model revealed that persistent AF, left atrial appendage ostial diameter and left atrial size were independent risk factors for IDE. During 6-month follow-up, the incidence of DRT was 4.6% in patients with IDE and 2.8% in those with CDE, respectively (p > 0.05), and the overall rate of MACCE was non-significantly higher in the IDE group (7.7% vs. 2.8%, p = 0.32).
Conclusion
IDE is common after LAAC, especially in patients with persistent AF, higher left atrial appendage ostial diameter and left atrial size. IDE confers an increased risk for DRT, but may be not necessarily associated with thromboembolic events and poor clinical outcome, providing careful monitoring and continued antithrombotic therapy are given.
... In the risk factor analysis for incomplete NE, we found that a larger device size could be attributable to it, consistent with previous findings in the left atrium appendage occluder devices and earlier case repo rts. 31,33,35,42,43 Additionally, our study showed that bulky shape (greater device thickness) was highly correlated with incomplete NE. Structural components of the device might interfere with the NE process; for instance, the fixed stainless steel pin buttons at the center of the device discs might interfere with NE. 44,45 Several reports showed a significant association between bulky shape with greater device thickness and incomplete device NE. 39,41 Although we suggested the cutoff of 21 mm as a predictor for incomplete NE, it is too early to use this value itself to make clinical decisions. ...
Background
Although the transcatheter closure of atrial septal defect was established as the treatment of choice several decades ago, the process of device neoendothelialization (NE) in humans is not well understood. We aimed to measure the extent of device NE using cardiac computed tomography angiography and analyze its risk factors.
Methods
Between January 2005 and February 2021, we retrospectively reviewed 164 devices of 112 patients on cardiac computed tomography angiography. We investigated device shape, contrast opacification within the device that differentiated device NE, and device-related thrombosis or vegetation. Risk factor analysis for major adverse cardiovascular events and incomplete NE according to the postprocedural period was performed.
Results
Seventy patients (62.5%) were women, with a median (range) age at the time of device closure of 44.5 (0.6–79.2) years. The mean (±SD) defect size was 16.6 (±7.8) mm, and patients were followed for 35.9±33.9 months. After 6 months of device implantation, 35% of the devices (42/120) had incomplete NE. The intensity of intradevice opacification shifted from complete to partial or nonopacification over time ( P <0.001), and a similar pattern was observed in the shunt flow ( P <0.001). The bulkiness of devices also decreased in proportion to the postprocedural period ( P <0.001). Risk analysis revealed device diameter (hazard ratio, 1.18 [95% CI, 1.04–1.27]; P <0.001) as the only significant factor of incomplete NE and major adverse events.
Conclusions
Incomplete NE of atrial septal defect devices was identified on cardiac computed tomography angiography in significant numbers after 6 months of the procedure. The device diameter was related to incomplete NE and major adverse events. Further prospective and multicenter studies are warranted to validate this new assessment of device NE.
... In canine models, the device surface is often completely endothelialized within3months after implantation [14,15].By contrast, IDEpost LAAC occurs frequently even well beyond this timeperiodin humans [11,13,17,18].In this study, almost two-thirds of patients had IDE detected by cardiac CT at 6 months post procedure, whichwas similar to most previous reports [22,24,25] [29].Lindner et al reported anIDE rate of 56% at median follow-up of 6 months post LAAC procedure [30]. Likewise, in another study including 46 patients undergoing successful LAAC, Sivasambu et alobserved that IDE occurred in 28 patients at 45 days during follow-up.Interestingly, cardiac CT demonstrated that contrast medium entered the left atrial appendage through the fabric rather than around the device in 10 patients [25].Conversely, Zhao and co-workers reported an IDE rate of 8.3% at 6 months in 84 patients who received successful LAAC and ablation of AF [31].The explanation for different occurrence rates of IDE after LAAC is multifactorial, and may be, at least partly, related toheterogenous de nitions of IDE, various types of LAA occluder, and different cardiac imaging techniques [14,30,32]. ...
... In canine models, the device surface is often completely endothelialized within3months after implantation [14,15].By contrast, IDEpost LAAC occurs frequently even well beyond this timeperiodin humans [11,13,17,18].In this study, almost two-thirds of patients had IDE detected by cardiac CT at 6 months post procedure, whichwas similar to most previous reports [22,24,25] [29].Lindner et al reported anIDE rate of 56% at median follow-up of 6 months post LAAC procedure [30]. Likewise, in another study including 46 patients undergoing successful LAAC, Sivasambu et alobserved that IDE occurred in 28 patients at 45 days during follow-up.Interestingly, cardiac CT demonstrated that contrast medium entered the left atrial appendage through the fabric rather than around the device in 10 patients [25].Conversely, Zhao and co-workers reported an IDE rate of 8.3% at 6 months in 84 patients who received successful LAAC and ablation of AF [31].The explanation for different occurrence rates of IDE after LAAC is multifactorial, and may be, at least partly, related toheterogenous de nitions of IDE, various types of LAA occluder, and different cardiac imaging techniques [14,30,32]. ...
... This may partly account for the higher prevalence of IDE in our study.Similar results have been demonstrated by Lindner [30,32],who de ned LAA as patent if attenuation of the left atrium exceeded that of the left atrial appendage by 50 HU. ...
Purpose
This study aimed to assess the incidence, potential risk factors and clinical impact of incomplete device endothelialization (IDE) after left atrial appendage closure (LAAC).
Methods
A total of 101 consecutive patients with nonvalvular atrial fibrillation (AF) who underwent successful LAAC and received antithrombotic treatment using a standard regimen were prospectively followed up to 6 months after the procedure. The status of device endothelialization and device-related thrombus (DRT) were evaluated using cardiac computed tomography (CT). Major adverse cardio-cerebral events (MACCE) including all-cause death, heart failure(HF) hospitalization, acute ischemic stroke, transient ischemic attack(TIA), peripheral vascular embolism, and major bleeding were recorded.
Results
IDE was detected in 65 (64.4%) patients. Patients with IDE or complete device endothelialization (CDE) did not significantly differ with respect to baseline clinical characteristics and interventional procedure features. Multivariate analysis model revealed that persistent AF, left atrial appendage ostial diameter and left atrial size were independent risk factors for IDE. During 6-month follow-up, the incidence of DRT was 4.6% in patients with IDE and 2.8% in those with CDE, respectively (p > 0.05), and the overall rate of MACCE was non-significantly higher in the IDE group (7.7% vs. 2.8%, p = 0.32).
Conclusions
IDE is common after LAAC, especially in patients with persistent AF, higher left atrial appendage ostial diameter and left atrial size. IDE confers an increased risk for DRT, but may be not necessarily associated with thromboembolic events and poor clinical outcome, providing careful monitoring and continued antithrombotic therapy are given.
... A previous study indicated that it would take about 30-90 days for occluders to be partially or completely endothelialized (Lindner et al., 2021). The implanted devices are more thrombogenic during the first few weeks after LAAC operation mainly due to their exposure to the circulating blood (Moons et al., 2002). ...
Background: The current post-procedure antithrombotic recommendation for left atrial appendage closure (LAAC) remains empiric. This study was designed to compare variations in platelet activation biomarkers and device-related thrombosis (DRT) under different antithrombotic regimens following LAAC.
Methods: This study enrolled 105 consecutive patients with atrial fibrillation who underwent LAAC successfully and received post-procedure anticoagulation with either dabigatran (N = 33) or rivaroxaban (N = 72). After 3 months of anticoagulation treatment, thromboelastogram was used to evaluate thrombin receptor–activating peptide (TRAP)–induced platelet aggregation (PA). Measurements of platelet activation biomarkers, including thrombin–antithrombin complex (TAT), P-selectin, von Willebrand disease (vWF), and CD40L, were performed immediately before the LAAC procedure and after 3 months of post-procedure anticoagulation. Repeated transesophageal echocardiography was performed to evaluate DRT during follow-ups.
Results: Three (4.2%) patients in the rivaroxaban and 4 (12.1%) patients in the dabigatran group experienced DRT events (odds ratio (OR) = 0.315, 95% confidence interval (95%CI): 0.066–1.489, p = 0.129) during follow-ups. The TRAP-induced PA was statistically significantly higher in the dabigatran group (62.9% vs 59.7%, p = 0.028*). Statistically significant increases in plasma concentration of TAT, P-selectin, and vWF were observed after 3 months of exposure to dabigatran when compared with rivaroxaban. An increased expression of platelet activation biomarkers was observed in DRT subjects compared with non–DRT subjects in terms of P-selectin and vWF (65.28 ± 13.93 ng/L vs 32.14 ± 12.11 ng/L, p = 0.037; 501.92 ± 106.48 U/L vs 280.98 ± 54.10 U/L, p = 0.045; respectively). Multivariate regression analysis indicated that the use of dabigatran might be an independent predictor of DRT (p = 0.022; OR = 4.366, 95%CI: 0.434–10.839). Furthermore, the CHA2DS2-VASc score (OR = 2.076, p = 0.016) and CD40L levels (OR = 1.015, p = 0.021) were independent predictors of increased D-dimer levels.
Conclusions: Post-LAAC anticoagulation with dabigatran may increase the risk of DRT by enhancing platelet reactivity. In light of this potential increased risk in DRT, the authors recommend against using dabigatran for post-procedural anticoagulation in patients who have undergone LAAC.
This study aimed to explore the endothelialization process and assess the potential association between endothelialization and peri-device leak (PDL) following Watchman implantation via a quantitative method.
This is a single-center retrospective study of consecutive patients undergoing LAAO between December 2015 and November 2021. Device endothelialization, compared between PDL and non-PDL group, were quantitatively analyzed based on hypoattenuated thickening in cardiac computed tomography angiography (CCTA). Advancement in endothelialization over time were explored using the Cochran-Armitage test and generalized estimating equation approach. Potential risk factors of delayed endothelialization were analyzed using the Cox proportional-hazards model.
A total of 172 patients (mean age, 68 years ± 10 [standard deviation], 114 men) were finally included. The average endothelialization ratio of the study population was 89.8 ± 7.2 percent. In the follow-up period of postprocedural 3 months to more than 12 months, an incremental trend of endothelialization over time was observed with the ratio of 85.8 ± 8.0, 89.6 ± 7.6, 92.2 ± 4.5, 94.3 ± 2.9 percent, respectively (p < 0.0001). Notably, patients without PDL exhibited a swifter advancement in endothelialization compared to those with PDL, irrespective of device size. The multivariable Cox regression model showed that PDL (HR = 2.113, 95%CI: 1.300–3.435, p = 0.003), DSP (HR = 1.717, 95%CI: 1.113–2.647, p = 0.014) were independent risk factors of delayed endothelialization.
CCTA holds promise as an effective means of quantitatively assessing device endothelialization. Endothelialization advanced gradually over time, with PDL potentially impeding device endothelialization.
A comprehensive understanding of the correlation between endothelialization ratio, time, and residual shunt can establish a more dependable foundation for determining the appropriate anticoagulation treatment following left atrial appendage closure.
Current recommendations for postleft atrial appendage occlusion anti-platelet and anticoagulation therapy are based on animal studies.
Cardiac computed tomography angiography (CCTA) combined with the UNet neural network model enables the quantitative assessment of device endothelialization.
This technique will allow for additional studies to better understand device endothelialization to optimize treatments in this population.
