-
Thrombosis Research Jun 2023Elderly people without atrial fibrillation (AF) still have a high incidence of cardioembolic stroke, suggesting that thrombus formation within the left atrial appendage...
The pathogenesis of aging-induced left atrial appendage thrombus formation and cardioembolic stroke in mice is influenced by inflammation-derived matrix metalloproteinases.
Elderly people without atrial fibrillation (AF) still have a high incidence of cardioembolic stroke, suggesting that thrombus formation within the left atrial appendage (LAA) may also occur in an AF-independent manner. In the present study, we explored the potential mechanisms for aging-induced LAA thrombus formation and stroke in mice. We monitored stroke events in 180 aging male mice (14-24 months) and assessed left atrium (LA) remodeling by echocardiography at different ages. Mice that had stroke were implanted with telemeters to confirm AF. Histological features of LA and LAA thrombi were examined, as well as collagen content, expression of matrix metalloproteinases (MMPs), and leukocyte density in the atria at different ages, in mice with or without stroke. Also, the effects of MMP inhibition on stroke incidence and atrial inflammation were tested. We detected 20 mice (11 %) with stroke, 60 % of which were within 18-19 months of age. Although we did not detect AF in mice with stroke, we detected the presence of LAA thrombi, suggesting that stroke originated from the hearts of these mice. Compared with 18-month-old mice without stroke, 18-month-old stroke mice had enlarged LA with a very thin endocardium, that was associated with less collagen and heightened MMP expression in the atria. During aging, we found that the expression of mRNAs for atrial MMP7, MMP8, and MMP9 peaked at 18 months, which closely correlated with reductions in collagen content and the time-window for cardioembolic stroke in these mice. Treatment of mice with an MMP inhibitor at 17-18 months of age reduced atrial inflammation and remodeling, and stroke incidence. Taken together, our study demonstrates that aging-induced LAA thrombus formation occurs through a mechanism involving upregulation of MMPs and breakdown of collagen, and that treatment with an MMP inhibitor may be effective as a treatment strategy for this heart condition.
Topics: Male; Animals; Mice; Atrial Fibrillation; Atrial Appendage; Embolic Stroke; Matrix Metalloproteinase Inhibitors; Echocardiography, Transesophageal; Heart Diseases; Thrombosis; Stroke; Inflammation; Collagen; Matrix Metalloproteinases
PubMed: 37121014
DOI: 10.1016/j.thromres.2023.04.020 -
Mathematical Biosciences and... Feb 2020The remodeling of the left atrial morphology and function caused by atrial fibrillation (AF) can exacerbate thrombosis in the left atrium (LA) even spike up the risk of...
The remodeling of the left atrial morphology and function caused by atrial fibrillation (AF) can exacerbate thrombosis in the left atrium (LA) even spike up the risk of stroke within AF patients. This study explored the effect of the AF on hemodynamic and thrombosis in LA. We reconstructed the patient-specific anatomical shape of the LA and considered the non-Newtonian property of the blood. The thrombus model was applied in the LA models to simulate thrombosis. Our results indicate that AF can aggravate thrombosis which mainly occurs in the left atrial appendage (LAA). Thrombosis first forms on the LAA wall then expands toward the internal LAA. The proposed computational model also shows the potential application of numerical analyses to help assess the risk of thrombosis in AF patients.
Topics: Atrial Appendage; Atrial Fibrillation; Heart Atria; Hemodynamics; Humans; Thrombosis
PubMed: 32233539
DOI: 10.3934/mbe.2020125 -
The Journal of Vascular Access May 2021Catheter-related right atrial thrombosis is an underestimated, severe, and life-threatening complication of any type of central venous catheters. No clear-cut...
BACKGROUND
Catheter-related right atrial thrombosis is an underestimated, severe, and life-threatening complication of any type of central venous catheters. No clear-cut epidemiological data are available. Catheter-related right atrial thrombosis is often asymptomatic; however, it can lead to serious complications and death.
CASE SERIES
We report seven catheter-related right atrial thrombosis events occurred in five hemodialysis patients; two recurrences following primary treatment are included in the report, all of them managed with a conservative approach without catheter removal. Systemic anticoagulation (vitamin K antagonists), having a well-defined target of International Normalized Ratio of 2.5-3.0, combined with urokinase as a locking solution at the end of each hemodialysis session were the therapeutic strategy used in all patients. After the first month, the anticoagulation target was reduced to an International Normalized Ratio value of 1.5-2.0 and urokinase to a weekly administration. After sixth months, when no thrombus was identified at transthoracic echocardiographic examinations, the treatment was stopped. No bleeding complications were reported.
CONCLUSION
The combination therapy here described is safe, quick, and effective, achieving the goal of not removing catheters.
Topics: Adult; Aged; Anticoagulants; Catheterization, Central Venous; Conservative Treatment; Female; Fibrinolytic Agents; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Renal Dialysis; Thrombosis; Treatment Outcome; Urokinase-Type Plasminogen Activator; Vitamin K
PubMed: 32410490
DOI: 10.1177/1129729820922703 -
Computers in Biology and Medicine Nov 2022We analyse the haemodynamics of the left atrium, highlighting differences between healthy individuals and patients affected by atrial fibrillation. The computational...
We analyse the haemodynamics of the left atrium, highlighting differences between healthy individuals and patients affected by atrial fibrillation. The computational study is based on patient-specific geometries of the left atria to simulate blood flow dynamics. We design a novel procedure to compute the boundary data for the 3D haemodynamic simulations, which are particularly useful in absence of data from clinical measurements. With this aim, we introduce a parametric definition of atrial displacement, and we use a closed-loop lumped parameter model of the whole cardiovascular circulation conveniently tuned on the basis of the patient's characteristics. We evaluate several fluid dynamics indicators for atrial haemodynamics, validating our numerical results in terms of clinical measurements; we investigate the impact of geometric and clinical characteristics on the risk of thrombosis. To highlight the correlation of thrombus formation with atrial fibrillation, according to medical evidence, we propose a novel indicator: age stasis. It arises from the combination of Eulerian and Lagrangian quantities. This indicator identifies regions where slow flow cannot properly rinse the chamber, accumulating stale blood particles, and creating optimal conditions for clots formation.
Topics: Humans; Atrial Fibrillation; Hydrodynamics; Heart Atria; Atrial Appendage; Hemodynamics; Thrombosis
PubMed: 36182758
DOI: 10.1016/j.compbiomed.2022.106143 -
Journal of Interventional Cardiology 2022The purpose of this study was to investigate the risk factors of left atrial (LA) or left atrial appendage (LAA) thrombi in patients with nonvalvular atrial fibrillation...
BACKGROUND
The purpose of this study was to investigate the risk factors of left atrial (LA) or left atrial appendage (LAA) thrombi in patients with nonvalvular atrial fibrillation (NVAF) and to establish and validate relevant predictive models. It might improve thromboembolic risk stratification in patients with NVAF.
METHODS
This study retrospectively included 1210 consecutive patients with NVAF undergoing transesophageal echocardiography (TEE), of whom 139 patients had thrombi in LA or in LAA. Through literature review and the ten events per variable (10EPV) principle, 13 variables were finally identified for inclusion in multivariate analysis. Models were constructed by multivariate logistic stepwise regression and least absolute shrinkage and selection operator (lasso) regression.
RESULTS
After logistic regression, five variables (AF type, age, B-type natriuretic peptide, /' ratio, and left atrial diameter) were finally screened out as model 1. After Lasso regression, AF type, age, gender, B-type natriuretic peptide, E/e' ratio, left atrial diameter, and left ventricular ejection fraction were finally screened as model 2. After comparing the two models, the simpler model 1 was finally selected. The area under the ROC curve (AUC) of the model 1 was 0.865 (95% CI: 0.838-0.892), the Hosmer-Lemeshow test = 0.898, and the AUC = 0.861 after internal validation. The clinical decision curve showed that the new clinical prediction model could achieve a net clinical benefit when the expected threshold was between 0 and 0.6.
CONCLUSION
This study constructed a new clinical prediction model of LA or LAA thrombi, with a higher discriminative degree than the CHADS2 and CHA2DS2-VASc scoring systems (AUC: 0.865 vs. 0.643; AUC: 0.865 vs 0.652).
Topics: Humans; Atrial Appendage; Atrial Fibrillation; Natriuretic Peptide, Brain; Stroke Volume; Retrospective Studies; Models, Statistical; Prognosis; Ventricular Function, Left; Thrombosis
PubMed: 36419956
DOI: 10.1155/2022/7806027 -
Clinical Cardiology Oct 2021Left atrial appendage (LAA) thrombus in patients with atrial fibrillation is usually detected by transesophageal echocardiography (TEE). Intracardiac echocardiography... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Left atrial appendage (LAA) thrombus in patients with atrial fibrillation is usually detected by transesophageal echocardiography (TEE). Intracardiac echocardiography (ICE) can be a suitable alternative to detect thrombosis. However, the effectiveness of the two methods for detecting LAA thrombus is still unclear, we performed a meta-analysis that compared ICE versus TEE for LAA thrombosis.
METHODS
We searched PubMed, Cochrane Library, and Embase for published abstracts and manuscripts on June 1, 2020. The analysis was performed using RevMan 5.3, STATA 15, and Meta-Disc 1.4.
RESULTS
Eight studies consists of 1108 patients (TEE = 558 vs. ICE = 550) were included. The average sensitivity of ICE and TEE to diagnose LAA thrombus is 1.0 (95% CI: 0.91-1.00) versus 0.68 (95% CI: 0.49-0.83), and specificity of ICE and TEE to diagnosis of LAA thrombus is 1.0 (95% CI: 0.99-1.00) versus 0.98 (95% CI: 0.96-0.99). The AUC of ICE and TEE is 0.9846 (SEAUC = 0.0196) and 0.9655 (SEAUC = 0.0401), and the Q* statistics is 0.9462 (SEQ* = 0.0406) and 0.9127 (SEQ * = 0.0616), respectively. Z test was performed on Q* statistics (Z = 0.45, p > .05).
CONCLUSION
The ICE and TEE have similar diagnostic efficacy for LAA thrombosis, but the ICE has higher sensitivity. Compared with TEE, ICE may be more advantages and prospects for clinical application.
Topics: Atrial Appendage; Atrial Fibrillation; Echocardiography, Transesophageal; Heart Diseases; Humans; Thrombosis
PubMed: 34480383
DOI: 10.1002/clc.23698 -
EuroIntervention : Journal of EuroPCR... Dec 2021Cardiac computed tomography angiography (CCTA) appears to be an appropriate imaging technique for device surveillance after left atrial appendage occlusion (LAAO)....
BACKGROUND
Cardiac computed tomography angiography (CCTA) appears to be an appropriate imaging technique for device surveillance after left atrial appendage occlusion (LAAO). However, the available experience is limited.
AIMS
The aim of this study was to determine the prevalence, mechanisms and clinical impact of left atrial appendage (LAA) patency and device-related thrombosis (DRT) following LAAO utilising a novel CCTA-based classification.
METHODS
Consecutively enrolled patients who underwent LAAO with an AMPLATZER device were followed up with CCTA. Mechanisms and frequency of residual patency were evaluated and correlated with clinical events. Atrial-side device thrombus, device positioning and presence of signs of device stability were also analysed.
RESULTS
A total of 137 patients were included. LAA patency was observed in 56.9% (n=78). Mechanisms and frequency of patency were: malapposition of proximal segment of the device lobe (55.1%), peri-device leak (PDL, 34.6%) and fabric permeability (5.8%). Lobe-LAA axis misalignment was the only independent predictor of device patency after LAAO (HR 38.3, 95% CI: 13.6-107.0; p<0.001). After a median follow-up of 638 days, patency was not associated with an increased risk of death (all-cause or cardiovascular death) or cerebral/peripheral embolism regardless of its mechanism. Any degree of hypo-attenuated thickening (HAT) was found in 16.8% (n=23) of patients, of whom 16 (11.7%) had low-grade HAT and 7 (5.1%) had high-grade HAT or definite DRT. Complete sealing was associated with increased rates of low-grade HAT.
CONCLUSIONS
LAA patency on CCTA follow-up is a frequent phenomenon due to malapposition of the proximal segment of the device lobe, PDL or fabric permeability. Patency was not associated with adverse outcomes. Low-grade HAT may be related to a benign, uneventful, endothelialisation process favoured by complete LAAO.
Topics: Atrial Appendage; Atrial Fibrillation; Echocardiography, Transesophageal; Humans; Prevalence; Septal Occluder Device; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 34219668
DOI: 10.4244/EIJ-D-21-00320 -
European Journal of Vascular and... Jan 2022
Topics: Accidents, Occupational; Aged; Echocardiography, Transesophageal; Heart Atria; Heart Diseases; Humans; Leg Injuries; Male; Thrombosis
PubMed: 34635398
DOI: 10.1016/j.ejvs.2021.09.003 -
Pacing and Clinical Electrophysiology :... Jul 2021Atrial fibrillation (AF), the most common arrhythmia, is a major cause of stroke and systemic embolism. Patients with AF are at higher risk of stroke with the left... (Review)
Review
Atrial fibrillation (AF), the most common arrhythmia, is a major cause of stroke and systemic embolism. Patients with AF are at higher risk of stroke with the left atrial appendage (LAA) being the most common site for thrombus formation. Although oral anticoagulation (OAC) remains the standard of care for stroke prevention in AF patients, there are still several limitations, including increased risk of bleeding and noncompliance. LAA closure (LAAC) has been found to be non-inferior to OAC in preventing all-cause strokes and systemic embolisms in randomized clinical trials, and is increasingly performed for stroke prevention in patients with nonvalvular AF (NVAF). However, device-related thrombus (DRT) after LAAC and a potentially increased risk of stroke related to DRT were observed in several registered studies, and attract wide concern. This review provides a comprehensive update on the incidence, mechanism, risk factors, prevention, diagnosis, and treatment of DRT after LAAC in patients with NVAF.
Topics: Atrial Appendage; Atrial Fibrillation; Cardiac Surgical Procedures; Humans; Postoperative Complications; Prostheses and Implants; Thrombosis
PubMed: 33165978
DOI: 10.1111/pace.14122 -
Cells Apr 2022Background: The present study aimed to explore the correlation between calcium-activated potassium channels, left atrial flow field mechanics, valvular atrial...
Background: The present study aimed to explore the correlation between calcium-activated potassium channels, left atrial flow field mechanics, valvular atrial fibrillation (VAF), and thrombosis. The process of transforming mechanical signals into biological signals has been revealed, which offers new insights into the study of VAF. Methods: Computational fluid dynamics simulations use numeric analysis and algorithms to compute flow parameters, including turbulent shear stress (TSS) and wall pressure in the left atrium (LA). Real-time PCR and western blotting were used to detect the mRNA and protein expression of IKCa2.3/3.1, ATK1, and P300 in the left atrial tissue of 90 patients. Results: In the valvular disease group, the TSS and wall ressure in the LA increased, the wall pressure increased in turn in all disease groups, mainly near the mitral valve and the posterior portion of the LA, the increase in TSS was the most significant in each group near the mitral valve, and the middle and lower part of the back of the LA and the mRNA expression and protein expression levels of IKCa2.3/3.1, AKT1, and P300 increased (p < 0.05) (n = 15). The present study was preliminarily conducted to elucidate whether there might be a certain correlation between IKCa2.3 and LA hemodynamic changes. Conclusions: The TSS and wall pressure changes in the LA are correlated with the upregulation of mRNA and protein expression of IKCa2.3/3.1, AKT1, and P300.
Topics: Atrial Fibrillation; Heart Atria; Hemodynamics; Humans; Potassium Channels, Calcium-Activated; RNA, Messenger
PubMed: 35563689
DOI: 10.3390/cells11091383