scholarly journals Large extracellular vesicles in the left atrial appendage in patients with atrial fibrillation—the missing link?

2021 ◽  
Author(s):  
Andreas Zietzer ◽  
Baravan Al-Kassou ◽  
Paul Jamme ◽  
Verena Rolfes ◽  
Eva Steffen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Vesicles ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Flow Cytometric Analysis ◽  
Heart Rhythm ◽  
Atrial Appendage ◽  
Peripheral Embolization

AbstractAtrial fibrillation (AF) is the most frequent arrhythmic disease in humans, which leads to thrombus formation in the left atrial appendage and stroke through peripheral embolization. Depending on their origin, large extracellular vesicles (lEVs) can exert pro-coagulant functions. In the present study, we investigated how different types of AF influence the levels of large EV subtypes in three distinct atrial localizations. Blood samples were collected from the right and left atrium and the left atrial appendage of 58 patients. 49% of the patients had permanent AF, 34% had non-permanent AF, and 17% had no history of AF. Flow cytometric analysis of the origin of the lEVs showed that the proportion of platelet-derived lEVs in the left atrial appendage was significantly higher in permanent AF patients compared to non-permanent AF. When we grouped patients according to their current heart rhythm, we also detected significantly higher levels of platelet-derived lEVs in the left atrial appendage (LAA) in patients with atrial fibrillation. In vitro studies revealed, that platelet activation with lipopolysaccharide (LPS) leads to higher levels of miR-222-3p and miR-223-3p in platelet-derived lEVs. Treatment with lEVs from LPS- or thrombin-activated platelets reduces the migration of endothelial cells in vitro. These results suggest that permanent atrial fibrillation is associated with increased levels of platelet-derived lEVs in the LAA, which are potentially involved in LAA thrombus formation.

Levels of platelet derived extracellular vesicles in the left atrial appendage are higher in patients with permanent atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Zietzer ◽  
B Al-Kassou ◽  
P Jamme ◽  
E Steffen ◽  
N Werner ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Vesicles ◽  
Platelet Activation ◽  
Right Atrium ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Atrial Appendage ◽  
Funding Source ◽  
The Right

Abstract Introduction Atrial fibrillation (AF) is a frequent arrhythmic disease and one of the most important causes of thrombembolic disease due to intracardiac thrombus formation. The left atrial appendage has been identified as the structure, where thrombus formation typically takes place in AF patients. Previous studies have shown thrombus formation is more frequent in permanent, than in paroxysmal or persistent AF. Underlying causes for this finding, however, remain unclear. Recently, it has been shown, that large extracellular vesicles (Microvesicles, MVs) are mediators of platelet activation. The aim of this study is therefore to investigate if the AF subtype correlates with the regional abundance of platelet derived MVs in the left atrial appendage. Methods and results In order to address this question blood samples from 59 consecutive patients undergoing left and right atrial catheterization were collected from the right atrium (RA), the left atrium (LA) and the left atrial appendage (LAA). 49% of the patients had permanent AF, 34% had non-permanent AF and 17% had no history of AF. MVs were isolated from 150 μL citrate plasma by a four-step differential centrifugation protocol (20000g x 40 min as main pelleting step). The MVs were characterized by immunoblotting and nanoparticle tracking analysis. The size of the MVs ranged between 50 and 600 nm and the MVs were shown to carry typical markers such as Annexin V. For flowcytometric analysis and quantification, Calcein AM was used to identify vesicles and CD31-PE, CD41-APC, CD235a-PE-Cy7 were applied to differentiate between platelet-derived MVs (PMVs, CD41+ CD31+), endothelial cell-derived MVs (EMVs, CD41- CD31+) and Red blood cell-derived MVs (RMVs, CD235a+). Fluorescence minus one controls, a concentration row and detergent mediated degradation were used to confirm specific staining of MVs. Total MV numbers (Calcein + events) did not differ significantly between the three cardiac localizations. In the left atrial appendage, the proportion of PMV was significantly higher in permanent AF patients compared to non-permanent AF. EMV numbers only differed in the right atrium, where permanent AF patients exhibited significantly lower numbers of EMVs compared to no AF controls. No differences between the groups were detected for RMV. Conclusion In the present study, we found that PMV levels in the left atrial appendage correlate with the type of atrial fibrillation (permanent vs non-permanent). PMVs have been connected to platelet activation and thrombus formation. These results may help to better understand how different types of atrial fibrillation cause different rates of thrombus formation in the LAA. PMV and EMV numbers by AF subtype Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical Faculty University Bonn

scholarly journals Effect of the Alterations in Contractility and Morphology Produced by Atrial Fibrillation on the Thrombosis Potential of the Left Atrial Appendage

2021 ◽  
Vol 9 ◽  
Author(s):  
Danila Vella ◽  
Alessandra Monteleone ◽  
Giulio Musotto ◽  
Giorgia Maria Bosi ◽  
Gaetano Burriesci
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Fluid Dynamic ◽  
Atrial Appendage ◽  
Primary Role ◽  
Shear Strain Rate ◽  
Increased Risk

Atrial fibrillation (AF) is a common arrhythmia mainly affecting the elderly population, which can lead to serious complications such as stroke, ischaemic attack and vascular dementia. These problems are caused by thrombi which mostly originate in the left atrial appendage (LAA), a small muscular sac protruding from left atrium. The abnormal heart rhythm associated with AF results in alterations in the heart muscle contractions and in some reshaping of the cardiac chambers. This study aims to verify if and how these physiological changes can establish hemodynamic conditions in the LAA promoting thrombus formation, by means of computational fluid dynamic (CFD) analyses. In particular, sinus and fibrillation contractility was replicated by applying wall velocity/motion to models based on healthy and dilated idealized shapes of the left atrium with a common LAA morphology. The models were analyzed and compared in terms of shear strain rate (SSR) and vorticity, which are hemodynamic parameters directly associated with thrombogenicity. The study clearly indicates that the alterations in contractility and morphology associated with AF pathologies play a primary role in establishing hemodynamic conditions which promote higher incidence of ischaemic events, consistently with the clinical evidence. In particular, in the analyzed models, the impairment in contractility determined a decrease in SSR of about 50%, whilst the chamber pathological dilatation contributed to a 30% reduction, indicating increased risk of clot formation. The equivalent rigid wall model was characterized by SSR values about one order of magnitude smaller than in the contractile models, and substantially different vortical behavior, suggesting that analyses based on rigid chambers, although common in the literature, are inadequate to provide realistic results on the LAA hemodynamics.

P4731Procedure-related acute thrombosis after surgical left atrial appendage occlusion for atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Inoue ◽  
T Shimizu ◽  
A Yoshimoto ◽  
Y Suematsu
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Cardiac Ct ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Atrial Appendage ◽  
Full Cohort ◽  
Exact Test ◽  
Acute Thrombosis ◽  
Laa Closure

Abstract Background/Introduction Left atrial appendage (LAA) occlusion is an effective strategy for thromboembolism prevention in patients with atrial fibrillation (AF), and the novel methods of occlusion is various. The acute thrombosis after percutaneous LAA occlusion devices has been recently reported, but thrombus formation after surgical LAA occlusion is still unclear. Purpose This study aimed to analyse the incidence and prognosis of thrombus formation on closure stump line in patients with AF who underwent surgical LAA occlusion. Methods This study retrospectively analised the data from patients treated with two methods of surgical LAA closure, resection or clipping, from January 2014 to November 2018. Results A total of 187 consecutive patients with AF underwent surgical LAA closure (31 clipping and 156 stapler resection). 170 patients (91%) underwent cardiac CT for LAA imaging on postoperative day 2. The incidence of acute procedure-related thrombus formation in full cohort was 19% (35 cases). The incidence of acute thrombus in patients with clipping and resection was 19% and 16%, respectively (Fisher's exact test, p=0.8). All of 35 patients who had thrombus on LAA closure stump line underwent cardiac CT again 3 months after the primary CT. In all patients with secondary cardiac CT, thrombus on LAA closure stump line disappeared. No symptomatic thromboembolism occurred during the follow-up from operation to secondary CT scan. Conclusion(s) Thrombus formation on stump after surgical LAA closure may often occur on acute phase. The optimal LAA imaging and anti-coagulation therapy after surgical LAA occlusion will prevent patients with acute thrombus from thromboembolism.

A Stunning Left Atrial Appendage Thrombus

Cardiology ◽  
2016 ◽  
Vol 134 (4) ◽  
pp. 394-397
Author(s):  
Sajid Ali ◽  
Justin Ugwu ◽  
Yousuf Kanjwal
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Atrial Flutter ◽  
Pulmonary Vein ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Atrial Appendage ◽  
Transesophageal Echocardiogram ◽  
Left Atrial Appendage Thrombus

Background: Left atrial appendage thrombus formation is a known major complication of atrial fibrillation and atrial flutter which increases the risk of embolism and stroke. This risk of thrombosis is greatly increased with a lack of anticoagulation. After conversion to a normal sinus rhythm in these arrhythmias, the risk of thrombus formation in the left atrium persists through a phenomenon termed atrial myocardial stunning. Case: We present the case of a patient who previously underwent successful pulmonary vein isolation and was found to be in typical isthmus-dependent atrial flutter with a questionable recurrence of atrial fibrillation. The decision was made to return for atrial flutter ablation and for evaluation of prior pulmonary vein isolation. Initially, a transesophageal echocardiogram showed a normal ejection fraction, biatrial enlargement and no left atrial appendage thrombus. Ablation of the cavotricuspid isthmus was successfully accomplished with documented bidirectional block. A transesophageal echocardiogram probe was still in place prior to planned transseptal puncture for the evaluation of pulmonary veins. A large thrombus was now observed filling the left atrial appendage. Conclusion and Objective: Atrial stunning is a transient atrial contractile dysfunction that occurs whether sinus rhythm is restored spontaneously, electrically, pharmacologically or by ablation. We know after conversion that there is higher propensity to increased spontaneous echogenic contrast and decreased velocities; however, we do not have documented knowledge of exactly how soon after the conversion to a sinus rhythm a thrombus may be seen. We demonstrate a case of acute left atrial appendage thrombus formation immediately following the successful ablation of isthmus-dependent atrial flutter. Our report validates the belief that strategies of not interrupting anticoagulation prior to the conversion of these arrhythmias should be implemented.

scholarly journals Inhibition of renin-angiotensin axis reduces the risk of thrombus formation in the left atrial appendage in patients with hypertension complicated by atrial fibrillation

2018 ◽  
Vol 19 (2) ◽  
pp. 147032031878262 ◽  
Author(s):  
Ya Suo ◽  
Zhiwei Zhang ◽  
Huaying Fu ◽  
Yue Zhang ◽  
Meng Yuan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Atrial Appendage ◽  
Renin Angiotensin ◽  
Echocardiographic Parameters ◽  
Hemostatic Markers ◽  
Ras Inhibitors

Aims: We examined whether the use of a renin-angiotensin-aldosterone system (RAS) inhibitor plays a role in protecting against left atrial appendage thrombus (LAAT) in patients with hypertension complicated by atrial fibrillation (AF). Methods: Two observational studies were conducted on patients with diagnoses of hypertension and AF, who were categorized into RAS inhibitor user or nonuser groups. Demographic characteristics, clinical characteristics, echocardiographic parameters and hemostatic markers were examined and the occurrence of LAAT during follow-up were recorded. Results: In the first study ( n = 131), LA peak systolic strain and LAA emptying flow velocity (LAA eV) were significantly increased in patients on RAS inhibitors compared with the nonuser group ( p < 0.05). Lower D-dimer and fibrinogen levels were observed in patients on RAS inhibitors ( p < 0.05). In the second study ( n = 99), 25.9% ( n = 11) of patients on RAS inhibitors developed LAAT, compared with 46.7% ( n = 21) in the nonuser group ( p < 0.05). After controlling for risk factors related to LAAT, use of RAS inhibitors remained associated with a significantly lower risk of developing LAAT (HR, 0.406; 95% CI, 0.191–0.862; p = 0.019). Conclusions: RAS inhibitors use was associated with a significant reduction in the risk of LAAT in patients with hypertension and AF.

Management of thrombus formation after electrical isolation of the left atrial appendage in patients with atrial fibrillation

EP Europace ◽  
2020 ◽  
Vol 22 (9) ◽  
pp. 1358-1366
Author(s):  
Thomas Fink ◽  
Feifan Ouyang ◽  
Christian-Hendrik Heeger ◽  
Vanessa Sciacca ◽  
Bruno Reissmann ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Cerebral Protection ◽  
Atrial Appendage ◽  
Protection Device ◽  
Left Atrial Appendage Thrombus ◽  
Electrical Isolation

Abstract Aims Left atrial appendage (LAA) electrical isolation (LAAEI) in addition to pulmonary vein isolation is an emerging catheter-based therapy to treat symptomatic atrial fibrillation. Previous studies found high incidences of LAA thrombus formation after LAAEI. This study sought to analyse therapeutic strategies aiming at the resolution of LAA thrombi and prevention of thromboembolism. Methods and results Left atrial appendage electrical isolation was conducted via creation of left atrial linear lesions or cryoballoon ablation. Follow-up including transoesophageal echocardiography was conducted. In patients with LAA thrombus, oral anticoagulation (OAC) was adjusted until thrombus resolution was documented. Percutaneous LAA closure (LAAC) under use of a cerebral protection device was conducted in case of medically refractory LAA thrombi. Left atrial appendage thrombus was documented in 54 of 239 analysed patients who had undergone LAAEI. Thrombus resolution was documented in 39/51 patients (72.2%) with available follow-up after adjustment of OAC. Twenty-nine patients underwent LAAC and 10 patients were kept on OAC after LAAEI. No thromboembolic events or further LAA thrombi were documented after 553 ± 443 days of follow-up in these patients. Persistent LAA thrombi despite adaption of OAC was documented in 12/51 patients. One patient remained on OAC until the end of follow-up, while LAAC with a cerebral protection device was performed in 11 patients in the presence of LAA thrombus without complications. Conclusion Left atrial appendage thrombus formation is common after LAAEI. Adjustment of OAC leads to LAA thrombus resolution in most patients. Left atrial appendage closure in the presence of LAA thrombi might be a feasible option in case of failed medical treatment.

Abstract 13136: Left Atrial Appendage Structural Characteristics Predict Thrombus Formation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hyun Kim ◽  
John Ning ◽  
Kaiwei Lu ◽  
Colton Thompson ◽  
Sudhi Tyagi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Structural Characteristics ◽  
Cross Sectional Area ◽  
Atrial Appendage ◽  
Case Group ◽  
Sectional Area ◽  
Cross Sectional

Introduction: Atrial fibrillation remains highly prevalent in the US with over 6 million diagnosed individuals. Discordant atrial contraction inherent to atrial fibrillation results in stagnant blood flow and increases the risk for thrombus formation particularly within the left atrial appendage (LAA). Anticoagulation is the mainstay of intracardiac thrombus prevention and is initiated based on the CHAD 2 S 2 -VASc risk score that does not account for LAA morphology. The relationship between LAA structural characteristics and thrombus development remains poorly understood. Hypothesis: We hypothesized that in patients with atrial fibrillation, LAA structural characteristics correlate with the presence of thrombus. Methods: We performed a retrospective case-control study of 151 subjects with a history of atrial fibrillation who underwent transesophageal echocardiogram (TEE) to evaluate the LAA for pre-cardioversion indication or Watchman screening evaluation. Subjects discovered to have LAA thrombus on TEE defined the study case group (n = 74) while control subjects did not have LAA thrombus (n = 77). Baseline demographics and echocardiographic characteristics were collected for all subjects. Results: Subjects without thrombus were older than those with thrombus (thrombus: 68.6 ± 13.1 years, no thrombus: 74.7 ± 9.2 years, p = 0.001 ). LAA ostial cross-sectional area was smaller in subjects with thrombus than those without thrombus (thrombus: 251.1 ± 117.4 mm 2 , no thrombus: 332.9 ± 171.2 mm 2 , p < 0.001 ). This finding remained significant in both unadjusted and adjusted logistic regression models ( Table 1 ). CHA 2 DS 2 -VASc score did not significantly differ in those with or without thrombus (thrombus: 4.4 ± 1.8, no thrombus: 4.3 ± 1.7, p = 0.822). Conclusions: Smaller LAA ostial cross-sectional area correlates with thrombus formation. Consideration of LAA structural characteristics may improve precision of anticoagulation management.

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