Risk of left atrial appendage thrombus and thromboembolism after left atrial appendage isolation for the treatment of atrial fibrillation: a meta-analysis

Risk of left atrial appendage thrombus and thromboembolism after left atrial appendage isolation for the treatment of atrial fibrillation: a meta-analysis | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 28 January 2025 V1 Latest version Share on Risk of left atrial appendage thrombus and thromboembolism after left atrial appendage isolation for the treatment of atrial fibrillation: a meta-analysis Authors : xiao Bai 0009-0001-4292-221X , Hao-Xin Huang , Zhen-Zhen Zhang , Juan-Juan Yuan , Sen Yan , and Xiao-Jun Xiang [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.173808920.08352186/v1 223 views 126 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract BACKGROUND Left atrial appendage (LAA) triggers play a crucial role in atrial fibrillation (AF) and can be effectively treated through complete LAA isolation. However, the current literature presents conflicting findings regarding the risks of LAA thrombus and thromboembolism after this procedure. Some researchers argue that the loss of contractility may lead to blood flow stasis, thereby increasing the risk of thrombus formation and thromboembolism in AF patients. In contrast, other clinical studies indicate that LAA isolation does not raise the risk of thrombus formation. OBJECTIVES The authors sought to perform a meta-analysis of controlled studies assessing the risk of LAA thrombus and thromboembolism in patients with AF undergoing isolation of the LAA. METHODS A systematic review of PubMed, Cochrane, and Embase was conducted for clinical studies published up to December 6, 2024, assessing the relationship between LAA isolation and thrombus formation. The primary endpoint was LAA thrombus formation or embolic events. The association between LAA isolation and thrombus formation was estimated using random-effects modeling. The risk ratio (RR) with 95% confidence intervals (CIs) was calculated using the DerSimonian and Laird method. RESULTS The study included five clinical studies with a total of 3,976 patients, of whom 851underwent LAA isolation. The analysis revealed that LAA isolation was associated with a significantly increased risk of LAA thrombus formation or transient ischemic attack (TIA)/stroke compared to those who did not undergo LAA isolation (RR 6.05, 95% CI 2.85–12.85; P < 0.0001; I 2 = 49%). The increased risk was particularly evident in prospective studies (RR 8.75, 95% CI 3.73–20.53; P < 0.0001; I 2 = 0%) and in studies with a follow-up period longer than two years (RR 7.39, 95% CI 4.4–12.41; P < 0.0001; I 2 = 15%). When focusing on well anticoagulated subjects, the major conclusion remained unchanged (RR 18.80, 95% CI 5.37–65.82; P < 0.0001; I 2 = 0%). Following LAA isolation, there was a significant decline in LAA flow velocity (SMD: -0.70; 95% CI: -1.33—0.07; p = 0.03; I 2 = 91%). In contrast, a significant increase in the degree of smoke in the LAA was observed (SMD: 1.33; 95% CI: 0.23–2.43; p = 0.02; I 2 = 95%) compared to preoperative function. CONCLUDE LAA isolation was associated with a significantly increased risk of LAA thrombus formation or thromboembolic events compared to those who did not undergo LAA isolation, even with ongoing anticoagulant therapy. More randomized trials are needed to explore safer ablation strategies that minimize the risk of thromboembolism after LAA isolation. Risk of left atrial appendage thrombus and thromboembolism after left atrial appendage isolation for the treatment of atrial fibrillation: a meta-analysis Xiao-Xia Bai 11Department of Cardiology, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China , Hao-Xin Huang a , Zhen-Zhen Zhang 22Department of Cardiology, First Hospital of Shanxi Medical University, School of Medicine, Shanxi Medical University, Taiyuan,030032, China , Juan-Juan Yuan 33Department of Cardiology, Characteristic Medical Center Of Chinese People’s Armed Police Force, Tianjin, 300162, China , Sen Yan a , Xiao-Jun Xiang a 44 * Corresponding author: Xiao-Jun Xiang, Secretary General of the Atrial Fibrillation Center and Heart Failure Center of Shanxi Bethune Hospital, E-mail: [email protected] , Tel:15333603606 Funding Shanxi Provincial Health and Wellness Commission’s Scientific Research Topic Plan for 2023 (2023012). Conflict of interest All authors declare no competing interests. Ethics approval Not applicable. Consent for publication Agree to publish. BACKGROUND Left atrial appendage (LAA) triggers play a crucial role in atrial fibrillation (AF) and can be effectively treated through complete LAA isolation. However, the current literature presents conflicting findings regarding the risks of LAA thrombus and thromboembolism after this procedure. Some researchers argue that the loss of contractility may lead to blood flow stasis, thereby increasing the risk of thrombus formation and thromboembolism in AF patients. In contrast, other clinical studies indicate that LAA isolation does not raise the risk of thrombus formation. OBJECTIVES The authors sought to perform a meta-analysis of controlled studies assessing the risk of LAA thrombus and thromboembolism in patients with AF undergoing isolation of the LAA. METHODS A systematic review of PubMed, Cochrane, and Embase was conducted for clinical studies published up to December 6, 2024, assessing the relationship between LAA isolation and thrombus formation. The primary endpoint was LAA thrombus formation or embolic events. The association between LAA isolation and thrombus formation was estimated using random-effects modeling. The risk ratio (RR) with 95% confidence intervals (CIs) was calculated using the DerSimonian and Laird method. RESULTS The study included five clinical studies with a total of 3,976 patients, of whom 851underwent LAA isolation. The analysis revealed that LAA isolation was associated with a significantly increased risk of LAA thrombus formation or transient ischemic attack (TIA)/stroke compared to those who did not undergo LAA isolation (RR 6.05, 95% CI 2.85–12.85; P < 0.0001; I² = 49%). The increased risk was particularly evident in prospective studies (RR 8.75, 95% CI 3.73–20.53; P < 0.0001; I² = 0%) and in studies with a follow-up period longer than two years (RR 7.39, 95% CI 4.4–12.41; P < 0.0001; I² = 15%). When focusing on well anticoagulated subjects, the major conclusion remained unchanged (RR 18.80, 95% CI 5.37–65.82; P < 0.0001; I² = 0%). Following LAA isolation, there was a significant decline in LAA flow velocity (SMD: -0.70; 95% CI: -1.33—0.07; p = 0.03; I² = 91%). In contrast, a significant increase in the degree of smoke in the LAA was observed (SMD: 1.33; 95% CI: 0.23–2.43; p = 0.02; I² = 95%) compared to preoperative function. CONCLUDE LAA isolation was associated with a significantly increased risk of LAA thrombus formation or thromboembolic events compared to those who did not undergo LAA isolation, even with ongoing anticoagulant therapy. More randomized trials are needed to explore safer ablation strategies that minimize the risk of thromboembolism after LAA isolation. 1 Introduction AF is one of the most common cardiac arrhythmias, with significant public health implications. Pulmonary vein isolation (PVI) is an accepted cornerstone for all AF ablation [1] and is an effective strategy for paroxysmal AF. However, in patients with persistent AF and long-standing persistent AF, PVI is associated with limited success. [2] The optimal ablation strategy has yet to be elucidated, although several ablation techniques adjunctive to PVI for persistent AF have been devised and attempted. [2] Recently, there has been a growing interest in the role of the left atrial appendage (LAA) in triggering and sustaining AF. The LAA is derived from the primitive atrium and is embryologically distinct from the left atrium. Studies have identified foci of enhanced automaticity in the LAA, and focal atrial tachycardias originating from this structure have been demonstrated in several studies. Enhanced automaticity from the LAA has been implicated in refractory AF and is thought to act as a trigger for refractory AF, particularly in patients with persistent AF or those with recurrence of AF after repeat ablation. Di Biase et al [3] demonstrated that the LAA may be responsible for AF recurrence in a subset of patients, and that isolation of the LAA could achieve freedom from AF in patients with demonstrated triggered activity. In this study, adjunctive LAA isolation significantly improved ablation success and did not increase the incidence of ischemic stroke events in patients who underwent LAA isolation. However, in an issue of Circulation: Arrhythmia and Electrophysiology, Rillig et al [4] identified an unexpectedly high rate of ischemic stroke and new thrombus formation in the LAA isolation group in their retrospective study. This study found that of 50 patients with LAA isolation, 10 and 3 patients experienced new thrombus formation and ischemic stroke or TIA, respectively. These findings raise serious concerns about the safety of LAA isolation within the context of extensive ablation procedures, and contrast with the results published by Di Biase et al. The aim of this study was to assess the relationship between LAA isolation and thrombus formation. To this end, we performed a systematic review and meta‐analysis. 2 Methods This meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines [5] and was registered with the International Prospective Register of Systematic Reviews (number CRD42024539371). 2.1 Data sources and searches We searched PubMed, Embase, and the Cochrane Central Register of Clinical Trials (Cochrane Library) using the following terms: “(left atrial appendage OR LAA OR left atrial appendage isolation) AND (thrombosis OR thrombus OR thromboses OR thromboembolism)” limited to clinical studies published as of December 12, 2023. Additionally, we performed hand searching with cross‐references of retrieved publications, review articles, and correspondence to ensure the inclusion of all relevant studies. Furthermore, we reviewed the bibliography of each included study to identify additional relevant studies not captured by other strategies. 2.2 Study selection Three authors (X.X.B., H.X.H., S.Y.) independently performed the initial screening of titles and abstracts to identify potentially relevant articles. Review articles, case reports, meeting abstracts, and single-armed studies of LAA isolation without a comparison group were excluded. In addition, we excluded the study of the LAA isolation group that performed LAA occlusion after ablation, because the relationship between thrombus formation and LAA isolation could not be clarified in this situation. The full text of selected articles was independently assessed by three authors (X.X.B., H.X.H., S.Y.) to determine relevance for inclusion. Conflicts were resolved by discussion between the assessors, and it was arranged that any disagreement would be resolved by discussion with the senior author (X.J.X.). The studies had to fulfil the following criteria to be included in the analysis: (i) the study was prospectively or retrospectively designed; (ii) the population was composed of patients undergoing LAA isolation for paroxysmal AF, persistent AF or long-standing persistent AF; (iii) the study had a LAA isolation group and a control group; (iv) reported incidence of thrombotic events in both groups. 2.3 Data extraction Three investigators (X.X.B.,H.X.H.,S.Y.) independently extracted information on study characteristics (author, study type and publication year), mean duration of follow-up, sample size, sex, mean age, type of AF, left atrial size or diameter, diabetes mellitus, hypertension, coronary artery disease, ablation techniques, mean left ventricular ejection fraction (LVEF) and LAA flow velocity after ablation. Any disagreements were resolved through consensus. 2.4 Primary outcomes The primary outcome was LAA thrombus formation or embolic events (TIA or stroke) assessed by transesophageal echocardiography (TEE) or through imaging evaluation during follow-up. 2.5 Quality assessment We used the Newcastle‐Ottawa Scale to assess the quality of the included studies from three broad perspectives: the selection of study groups, comparability of the groups, and ascertainment of exposure and outcomes of interest. Nine points were available to be awarded based on (a) representativeness of the exposed cohort, (b) selection of the nonexposed cohort, (c) exposure ascertainment, (d) the absence of the outcome of interest at the study’s onset, (e) study controls for left atrial size, (f) study controls for other factors, (g) assessment of outcomes, (h) follow‐up long enough for outcomes to occur, and (i) adequacy of control outcomes. Studies were categorized as: (a) high quality: seven to nine points; (b) fair quality: four to six points; or (c) poor quality: zero to three points. 2.6 Statistical analysis We performed a Random-Effects Model to evaluate the relationship between LAA isolation and thrombus formation, using the DerSimonian and Laird method to compute relative risks (RRs) with 95% confidence intervals (CIs) based on event counts. Sensitivity analyses were conducted by serially excluding individual studies. Descriptive statistics are presented as means and standard deviations (SDs) for continuous variables, and as number of cases (n) and percentages (%) for dichotomous and categorical variables. Statistical analyses followed the recommendations from the Cochrane Collaboration and PRISMA guidelines, using Review Manager (RevMan), version 5.3, from the Cochrane Collaboration, 2014. Heterogeneity was assessed using the I² statistic, which represents the proportion of total variation among the studies attributable to differences between studies rather than sampling error. [6] We considered I² less than 25% as low and greater than 75% as high. The Random-Effects Model of DerSimonian and Laird was employed if I² was greater than 25%. [7] Publication bias was estimated visually using funnel plots. 3 Results 3.1 study selection We identified 1491 abstracts, out of which 1431 were removed after title review. A total of 56 abstracts were retrieved and carefully reviewed for possible inclusion（Figure 1）. Sixteen full-text manuscripts were assessed for eligibility. Five studies (Tables 1 and 2) with a total of 3976 patients fulfilled the inclusion criteria and were included in the present meta-analysis [12,11,10,9,4] Two of these were prospective observational studies, [10,4] One was a retrospective observational study [12] and two were retrospective observational studies with propensity matching. [11,9] Key details regarding each study are presented in Table 2. 3.2 quality assessment All the studies included in this meta-analysis had good methodological quality, indicating a ‘low risk of bias’ (Supplementary Table S1). All five studies were classified as high-quality based on the Newcastle Ottawa Assessment scale using nine different parameters. 3.3 Patient characteristics The study included five clinical studies with a total of 3,976 patients, of whom 851underwent LAA isolation. The ablation strategy in all studies included PVI (or reisolation) with adjunctive ablation that varied by study. A majority of the studies employed wide-area LAA isolation strategy, and relevant details are presented in Table 2. The follow-up duration extended from 6.8 to 60 months, with the majority of studies having follow-up periods exceeding 1 year. Within the included studies, only a single study utilized cryoballoon (CB)-based empirical LAA isolation, [9] with the remainder relying on radiofrequency catheter ablations. The Patients were generally older men with hypertension, nonparoxysmal AF, a preserved ejection fraction, and an enlarged left atrium. Baseline characteristics in all studies were comparable in both groups. The baseline characteristics of the study patients, when stratified by study and LAA isolation versus no LAA isolation, have been detailed in Table 1. 3.4 Outcomes analysis LAA isolation was associated with a significantly increased risk of LAA thrombus formation or thromboembolic events compared to those who did not undergo LAA isolation (RR 6.05, 95% CI 2.85–12.85; P < 0.0001; I² = 49%) during a follow-up period of 6.8 to 60 months, as illustrated in Figure 2. In contrast, retrospective observational studies did not demonstrate significant differences between the groups (RR 3.63, 95% CI 0.83–15.83; P =0.09; I 2 = 78%), However, prospective observational studies indicated a significantly higher risk of thrombus formation associated with LAA isolation (RR 8.75, 95% CI 3.73–20.53; P < 0.0001; I 2 = 0%). Figure 2: Meta-analysis of incidence of LAA thrombus and thromboembolism after LAA isolation depending on Prospective observational or Retrospective observational studies; CI, confidence interval; LAA, left atrial appendage; PVI, pulmonary vein isolation; M-H, Mantel–Haenszel test. In a subgroup analysis based on follow-up period, adjunctive LAA isolation was shown to significantly increase the risk of LAA thrombus and thromboembolism when only patients with a follow-up period longer than two years were considered (RR 7.39, 95% CI 4.4–12.41; P < 0.0001; I 2 = 15%), However, no significant risk was observed in the subgroup of studies with a follow-up of less than two years (RR 3.46, 95% CI 0.05–229.84; P =0.56; I 2 = 81%) (Figure 3). Following LAA isolation, there was a significant decline in LAA flow velocity (SMD: -0.70; 95% CI: -1.33—0.07; p = 0.03; I² = 91%) (Figure 5A). In contrast, a significant increase in the degree of smoke in the LAA was observed (SMD: 1.33; 95% CI: 0.23–2.43; p = 0.02; I² = 95%) (Figure 5B) compared to preoperative function. Considering that the link to discontinuation of anticoagulants is expected and further contaminates the conclusions, we focused on well-anticoagulated subjects to compare the two groups of events under anticoagulation, revealing significant differences (RR 18.80, 95% CI 5.37–65.82; P < 0.0001; I 2 = 0%) (Figure 4). Consequently, adjunctive LAA isolation is associated with an increased risk of LAA thrombus formation or thromboembolic events. Figure 4: Meta-analysis of incidence of events under anticoagulation ; CI, confidence interval; LAA, left atrial appendage; PVI, pulmonary vein isolation; M-H, Mantel–Haenszel test. （A） Figure 5: (A) Forest plot of LAA flow velocity. (B) Forest plot of degree of smoke in LAA. CI, confidence interval; LAA, left atrial appendage. Figure 3: Meta-analysis of incidence of LAA thrombus and thromboembolism after LAA isolation depending on the duration of follow-up >2years or < 2years; CI, confidence interval; LAA, left atrial appendage; PVI, pulmonary vein isolation; M-H, Mantel–Haenszel test. 3.5 Heterogeneity evaluation, sensitivity analyses and publication biases Heterogeneity was noted to be higher in main of the outcomes we studied. We subsequently excluded individual studies, identifying that Yorgun et al [9] contributed significantly to this heterogeneity. Omitting Yorgun et al [9] reduced the I² statistic from 49% to 0%, with no significant changes to the results (Supplemental Figure S1). Given the different ablation techniques, we categorized the studies by ablation method and considered the heterogeneity originating from these techniques in our analysis (Supplemental Figure S2). In a series of sensitivity analyses with sequential removal of individual studies, the results remained consistent with the primary analysis (Supplemental Figure S3). Additionally, no publication biases were noticed by analysis of funnel plots performed for each comparison (Supplementary Figures S4). 4 Discussion This is the first study to primarily report embolic events in AF patients underwent LAA isolation. we included five studies with a large group of 3,976 patients, with follow-up durations ranging from 6.8 to 60 months. The key findings of this meta-analysis are as follows: (1) LAA isolation was associated with a significantly increased risk of LAA thrombus formation or TIA/stroke compared to those who did not undergo LAA isolation. The increased risk was particularly evident in prospective studies and in studies with a follow-up period longer than two years. (2) When focusing on well anticoagulated subjects, the major conclusion remained unchanged. (3) Following LAA isolation, there was a significant decline in LAA flow velocity. In contrast, a significant increase in the degree of smoke in the LAA was observed compared to preoperative function. The prevalence of triggers firing from the LAA and the optimal strategy to eliminate these foci to increase the procedural success rate were initially reported by Di Biase et al. [3] Their investigation uncovered that 27% of patients exhibited firing from the LAA, with 8.7% having the LAA as the sole source of arrhythmia. Furthermore, the study demonstrated that complete isolation of the LAA was superior to focal ablation. Nonetheless, the long-term thromboembolic risk and appropriate management of real-world patients underwent LAA isolation remain subjects of contention. In response to this controversy, we conducted a study, the results of which indicated that isolation of the LAA significantly increases the risk of LAA thrombus formation or thromboembolic events. This finding aligns with the previous conclusions drawn by Rillig et al. [4] However, Di Biase et al [3] reported that thrombus was not observed in any of the 204 patients with LAA isolation, nor were any cerebrovascular events documented. This stands in stark contrast to our data. According to the findings of prior studies, the status of anticoagulant usage and the strategies of LAA isolation exert the most profound influence on thrombotic events. Consequently, our discussion primarily revolves around the distinctions in these two domains. This study revealed that LAA isolation was associated with a significantly increased risk of LAA thrombus formation or thromboembolic events compared to those who did not undergo LAA isolation, even with ongoing anticoagulant therapy. Rillig et al [4] reported high incidence of LAA thrombus formation and stroke in post-LAA isolation cases despite proportion of events under anticoagulation 92.3%. This study found that the mean flow velocity of LAA after isolation was 0.21 m/s (<0.4m/s), indicating compromised LAA function, which may have contributed to the elevated incidence of thrombus formation and strokes. Similarly, Kim et al [12] reported high stroke-risk in patients with LAA isolation, with 88.9% of events occurring under anticoagulation. Furthermore, patients who underwent LAA isolation exhibited a significant reduction in LAA flow velocity post-procedure. The findings of Heeger et al [10] paralleled those of Kim. Our analysis revealed that the ablation strategies employed in these studies were largely analogous, utilizing a wider area of ablation strategy to isolate LAA. Such an extensive ablation may have compromised overall atrial contraction, potentially creating a prothrombotic environment. Additionally, these studies encompassed patients with paroxysmal AF, for whom linear lesions have limited efficacy, thereby posing an unnecessary risk to the patients. The isolation strategy with segmental LAA isolation in or at the LAA base of Biase et al, On the contrary, is more conservative. [3] Most patients in this study did not exhibit impaired LAA function. Intriguingly, those with preserved LAA function did not suffer any stroke events, whereas 5.9% of patients with impaired function reported thromboembolic events. [13] These findings suggested a decline in LAA function following LAA isolation, which may predispose patients to thrombus formation, even on-anticoagulation. The LAA flow velocity is significantly impaired that might is a reliable predictor of future embolic events in patients with LAA isolation. A 2019 study revealed that the overall incidence of thromboembolic events was significantly higher among those patients who discontinued anticoagulants in the presence of impaired LAA function. [13] Romero et al [11] found that the rates of TIA and stroke differed significantly between the LAA isolation group and those non-LAA isolation. Thromboembolic event rate was significantly higher in the LAA isolation group. It is noteworthy that all thromboembolic events occurred in off- anticoagulant patients. This underscores the heightened risk of thromboembolism following LAA isolation when abnormal LAA function is present, even with anticoagulation. The danger of thromboembolism escalates in the presence of both impaired LAA function and the discontinuation of anticoagulants. Study of Romero et al [11] demonstrated the necessity for lifelong anticoagulation in patients underwent LAA isolation, regardless of their CHA2DS2-VASc score. Prior research has indicated that LAA flow velocity might not fully reflect the actual blood flow. Consequently, decisions regarding anticoagulation treatment for patients with LAA isolation should not be solely based on the LAA flow velocity. Anticoagulation should be continued in all patients underwent LAA isolation irrespective of the transesophageal echocardiography determined LAA velocities. Published observational studies have reported excellent results with LAA occlusion after LAA isolation, with a low risk of embolic strokes even in patients in whom anticoagulation has been completely stopped. [14] For patients who are unable tolerate anticoagulants agents, or have a contra‐ indication, LAA closure is considered an effective alternative with less risk of bleeding. We discovered that the increased risk was particularly evident in studies with a follow-up period longer than two years. In a prolonged follow-up extending beyond four years, Kim et al identified a clear increase in clinical events, including ischemic stroke or TIA, in patients with LAA isolation compared to those without isolation. The majority of the studies we reviewed had an average follow-up duration surpassing four years, in contrast to the six months noted by Biase et al. This disparity may also account for the variation in findings. However, we cannot deny that other sources of embolism may evolve over this time. Furthermore, LAA isolation may occur inadvertently following ethanol ablation of the Marshall vein or other extensive ablation procedures that do not specifically target the LAA. Expanding on these scenarios would provide a more comprehensive understanding of the broader applications and potential risks associated with LAA isolation. 5 Limitations The limited data and combining prospective and retrospective data available is a weakness of the analysis. The availability of complete TEE data including smoke severity and flow velocities before and after ablation is not adequate, which limited our ability to further explore the function of the LAA in relation to endpoint events. Additionally, there exist some uncertainty regarding the actual ablation approaches in some studies. Intraprocedural differences related to operators’ experience may have occurred between studies and centers. Although no clear publication bias was demonstrable, the current tools for the assessment of publication bias are likely underpowered given the small number of studies. Periprocedural complications were not uniformly recorded, which precludes robust analyses on periprocedural safety. Finally, the incidence rates for our primary outcomes were infrequently available, and therefore, raw event counts were used for all statistical analysis. 6 Conclusion LAA isolation was associated with a significantly increased risk of LAA thrombus formation or thromboembolic events compared to those who did not undergo LAA isolation, even with ongoing anticoagulant therapy. More randomized trials are needed to explore safer ablation strategies that minimize the risk of thromboembolism after LAA isolation. [1] Hwang C, Wu T J, Doshi R N, et al. Vein of marshall cannulation for the analysis of electrical activity in patients with focal atrial fibrillation[J]. Circulation, 2000, 101(13): 1503–1505. [2] Tilz R R, Rillig A, Thum A-M, et al. Catheter ablation of long-standing persistent atrial fibrillation: 5-year outcomes of the Hamburg Sequential Ablation Strategy[J]. Journal of the American College of Cardiology, 2012, 60(19): 1921–1929. [3] Di Biase L, Burkhardt J D, Mohanty P, et al. Left atrial appendage: an underrecognized trigger site of atrial fibrillation[J]. Circulation, 2010, 122(2): 109–118. [4] Rillig A, Tilz R R, Lin T, et al. Unexpectedly High Incidence of Stroke and Left Atrial Appendage Thrombus Formation After Electrical Isolation of the Left Atrial Appendage for the Treatment of Atrial Tachyarrhythmias[J]. Circulation. Arrhythmia and Electrophysiology, 2016, 9(5): e003461. [5] Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement - PubMed[EB/OL]. /2024-07-30. https://pubmed.ncbi.nlm.nih.gov/19622511/. [6] Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement[J]. BMJ (Clinical research ed.), 2009, 339: b2535. [7] DerSimonian R, Laird N. Meta-analysis in clinical trials[J]. Controlled Clinical Trials, 1986, 7(3): 177–188. [8] Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test[J]. BMJ (Clinical research ed.), 1997, 315(7109): 629–634. [9] Yorgun H, Canpolat U, Kocyigit D, et al. Left atrial appendage isolation in addition to pulmonary vein isolation in persistent atrial fibrillation: one-year clinical outcome after cryoballoon-based ablation[J]. Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology: Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology, 2017, 19(5): 758–768. [10] Heeger C-H, Rillig A, Geisler D, et al. Left Atrial Appendage Isolation in Patients Not Responding to Pulmonary Vein Isolation[J]. Circulation, 2019, 139(5): 712–715. [11] Romero J, Di Biase L, Mohanty S, et al. Long-Term Outcomes of Left Atrial Appendage Electrical Isolation in Patients With Nonparoxysmal Atrial Fibrillation: A Propensity Score-Matched Analysis[J]. Circulation. Arrhythmia and Electrophysiology, 2020, 13(11): e008390. [12] Kim Y G, Shim J, Oh S-K, et al. Electrical isolation of the left atrial appendage increases the risk of ischemic stroke and transient ischemic attack regardless of postisolation flow velocity[J]. Heart Rhythm, 2018, 15(12): 1746–1753. [13] Huizar J F, Ellenbogen K A, Tan A Y, et al. Arrhythmia-Induced Cardiomyopathy: JACC State-of-the-Art Review[J]. Journal of the American College of Cardiology, 2019, 73(18): 2328–2344. [14] Zender N, Weise F K, Bordignon S, et al. Thromboembolism after electrical isolation of the left atrial appendage: a new indication for interventional closure? [J]. Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology: Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology, 2019, 21(10): 1502–1508. Supplementary Material File (image6.emf) Download 1016.00 KB File (image7.emf) Download 600.12 KB Information & Authors Information Version history V1 Version 1 28 January 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords clinical: catheter ablation – atrial fibrillation clinical: electrophysiology – atrial arrhythmias Authors Affiliations xiao Bai 0009-0001-4292-221X Shanxi Bethune Hospital View all articles by this author Hao-Xin Huang Shanxi Bethune Hospital View all articles by this author Zhen-Zhen Zhang First Hospital of Shanxi Medical University View all articles by this author Juan-Juan Yuan Characteristic Medical Center of People's Armed Police Force View all articles by this author Sen Yan Shanxi Bethune Hospital View all articles by this author Xiao-Jun Xiang [email protected] Shanxi Bethune Hospital View all articles by this author Metrics & Citations Metrics Article Usage 223 views 126 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation xiao Bai, Hao-Xin Huang, Zhen-Zhen Zhang, et al. Risk of left atrial appendage thrombus and thromboembolism after left atrial appendage isolation for the treatment of atrial fibrillation: a meta-analysis. 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