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Archives of Cardiovascular Diseases Oct 2020
Topics: Atrial Appendage; Heart Atria; Heart Diseases; Humans; Thrombosis
PubMed: 32958416
DOI: 10.1016/j.acvd.2020.08.001 -
Medical Ultrasonography Mar 2023
Topics: Humans; Atrial Fibrillation; Thrombosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Heart Atria
PubMed: 36996396
DOI: 10.11152/mu-4017 -
Clinical and Translational Medicine Jun 2023Atrial fibrillation (AF) is associated with an increased risk of thrombosis of the left atrial appendage (LAA). However, the molecular mechanisms underlying this...
BACKGROUND
Atrial fibrillation (AF) is associated with an increased risk of thrombosis of the left atrial appendage (LAA). However, the molecular mechanisms underlying this site-specificity remain poorly understood. Here, we present a comparative single-cell transcriptional profile of paired atrial appendages from patients with AF and illustrate the chamber-specific properties of the main cell types.
METHODS
Single-cell RNA sequencing analysis of matched atrial appendage samples from three patients with persistent AF was evaluated by 10× genomics. The AF mice model was created using Tbx5 knockout mice. Validation experiments were performed by glutathione S-transferase pull-down assays, coimmunoprecipitation (Co-IP), cleavage assays and shear stress experiments in vitro.
RESULTS
In LAA, phenotype switching from endothelial cells to fibroblasts and inflammation associated with proinflammatory macrophage infiltration were observed. Importantly, the coagulation cascade is highly enriched in LAA endocardial endothelial cells (EECs), accompanying the up-regulation of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) and the down-regulation of the tissue factor pathway inhibitor (TFPI) and TFPI2. Similar alterations were verified in an AF mouse model (Tbx5 ) and EECs treated with simulated AF shear stress in vitro. Furthermore, we revealed that the cleavage of both TFPI and TFPI2 based on their interaction with ADAMTS1 would lead to loss of anticoagulant activities of EECs.
CONCLUSIONS
This study highlights the decrease in the anticoagulant status of EECs in LAA as a potential mechanism underlying the propensity for thrombosis, which may aid the development of anticoagulation therapeutic approaches targeting functionally distinct cell subsets or molecules during AF.
Topics: Animals; Mice; Atrial Fibrillation; Atrial Appendage; Endothelial Cells; Thrombosis; Anticoagulants; Sequence Analysis, RNA
PubMed: 37278111
DOI: 10.1002/ctm2.1297 -
Journal of Clinical Ultrasound : JCU Oct 2022Atrial fibrillation (AF) is the most common arrhythmia in the general population. Systemic thromboembolism from left atrial appendage (LAA) thrombosis is a well-known... (Review)
Review
Atrial fibrillation (AF) is the most common arrhythmia in the general population. Systemic thromboembolism from left atrial appendage (LAA) thrombosis is a well-known complication of AF, whereas thromboembolic complications from a right atrial (RA) thrombus are infrequent. Nevertheless, the prevalence of RA thrombosis is debated; despite having a low prevalence in echocardiographic studies, the higher prevalence found in autoptic studies rises the hypothesis of an under detection of RA clots, possibly related to the limited evaluation of right atrial appendage (RAA) with non-invasive imaging. Here we present a review of the current literature about RA thrombosis, regarding its diagnosis, differentials, and best treatment options.
Topics: Atrial Appendage; Atrial Fibrillation; Echocardiography, Transesophageal; Heart Diseases; Humans; Risk Factors; Thrombosis
PubMed: 36218213
DOI: 10.1002/jcu.23311 -
Journal of the American College of... Aug 2023Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness.
BACKGROUND
Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness.
OBJECTIVES
This study aimed to investigate RA function using pressure-volume (PV) loops, isolated cardiomyocyte, and histological analyses.
METHODS
RA PV loops were constructed in control subjects (n = 9) and precPH patients (n = 27) using magnetic resonance and catheterization data. RA stiffness (pressure rise during atrial filling) and right atrioventricular coupling index (RA minimal volume / RV end-diastolic volume) were compared in a larger cohort of patients with moderate (n = 39) or severe (n = 41) RV diastolic stiffness. Cardiomyocytes were isolated from RA tissue collected from control subjects (n = 6) and precPH patients (n = 9) undergoing surgery. Autopsy material was collected from control subjects (n = 6) and precPH patients (n = 4) to study RA hypertrophy, capillarization, and fibrosis.
RESULTS
RA PV loops showed 3 RA cardiac phases (reservoir, passive emptying, and contraction) with dilatation and elevated pressure in precPH. PrecPH patients with severe RV diastolic stiffness had increased RA stiffness and worse right atrioventricular coupling index. Cardiomyocyte cross-sectional area was increased 2- to 3-fold in precPH, but active tension generated by the sarcomeres was unaltered. There was no increase in passive tension of the cardiomyocytes, but end-stage precPH showed reduced number of capillaries per mm accompanied by interstitial and perivascular fibrosis.
CONCLUSIONS
RA PV loops show increased RA stiffness and suggest atrioventricular uncoupling in patients with severe RV diastolic stiffness. Isolated RA cardiomyocytes of precPH patients are hypertrophied, without intrinsic sarcomeric changes. In end-stage precPH, reduced capillary density is accompanied by interstitial and perivascular fibrosis.
Topics: Humans; Myocytes, Cardiac; Hypertension, Pulmonary; Atrial Fibrillation; Heart Atria; Atrial Appendage
PubMed: 37587582
DOI: 10.1016/j.jacc.2023.05.063 -
JACC. Cardiovascular Interventions Jun 2019The aim of this study is to review the evidence on the use of antithrombotic therapy and risk of device-related thrombosis after left atrial appendage closure. (Review)
Review
OBJECTIVES
The aim of this study is to review the evidence on the use of antithrombotic therapy and risk of device-related thrombosis after left atrial appendage closure.
BACKGROUND
Left atrial appendage closure (LAAC) is increasingly performed for stroke prevention in patients with nonvalvular atrial fibrillation, especially those who cannot tolerate or are ineligible for oral anticoagulation.
METHODS
After device implantation for LAAC, different antithrombotic regimens with varying duration of therapy are currently used. Such selection depends on patients' risk for bleeding and physicians' choice.
RESULTS
Device-related thrombosis remains an Achilles' heel of LAAC, and the etiology remains incompletely understood. Dual-antiplatelet therapy, and direct oral anticoagulation may have similar safety and device-related thrombosis occurrence in real-world LAAC registries compared with warfarin and aspirin. Device imaging surveillance should be routinely performed to assess for device-related thrombosis, which if diagnosed should be treated aggressively, as it is associated with higher thromboembolic risks.
CONCLUSIONS
Given the uncertainties and therapeutic dilemma, the authors provide an in-depth discussion of the options and rationale for antithrombotic therapy post-LAAC.
Topics: Animals; Atrial Appendage; Atrial Fibrillation; Atrial Function, Left; Endovascular Procedures; Fibrinolytic Agents; Humans; Prosthesis Design; Risk Assessment; Risk Factors; Thrombosis; Time Factors; Treatment Outcome
PubMed: 31103535
DOI: 10.1016/j.jcin.2018.11.001 -
Medicina (Kaunas, Lithuania) Aug 2019Atrial fibrillation is the most common cardiac arrhythmia and is associated with an increased risk of stroke and thromboembolic complications. A rhythm control strategy... (Review)
Review
Atrial fibrillation is the most common cardiac arrhythmia and is associated with an increased risk of stroke and thromboembolic complications. A rhythm control strategy with both electrical and pharmacological cardioversion is recommended for patients with symptomatic atrial fibrillation. Anticoagulant therapy for 3-4 weeks prior to cardioversion is recommended in order to avoid thromboembolic events deriving from restoring sinus rhythm. Transesophageal echocardiography has a pivotal role in this setting, excluding the presence of left atrial appendage thrombus before cardioversion. The aim of this review is to discuss the epidemiology and risk factors for left atrial appendage thrombosis, the role of echocardiography in the decision making before cardioversion, and the efficacy of different anticoagulant regimens on the detection and treatment of left atrial appendage thrombosis.
Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Echocardiography; Echocardiography, Transesophageal; Electric Countershock; Heart Diseases; Humans; Risk Factors; Thrombosis; Warfarin
PubMed: 31438560
DOI: 10.3390/medicina55090511 -
Journal of Thrombosis and Haemostasis :... May 2023Oral anticoagulation therapy has evolved beyond vitamin K antagonists to include oral direct thrombin inhibitors and factor Xa inhibitors. Collectively known as "direct...
Recommendation on the nomenclature for anticoagulants: updated communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Commitee on the Control of Anticoagulation.
Oral anticoagulation therapy has evolved beyond vitamin K antagonists to include oral direct thrombin inhibitors and factor Xa inhibitors. Collectively known as "direct oral anticoagulants," this class of medications represents the current standard of care for the prevention and treatment of common thrombotic disorders, including atrial fibrillation and venous thromboembolism. Medications that target factors XI/XIa and XII/XIIa are currently under investigation for several thrombotic and nonthrombotic conditions. Given that these emerging medications will likely have distinct risk-benefit profiles to the current direct oral anticoagulants, may have different routes of administration, and could be used for unique clinical conditions (e.g., hereditary angioedema), the International Society on Thrombosis and Haemostasis Subcommittee on Control of Anticoagulation assembled a writing group to make recommendations on the nomenclature of anticoagulant medications. With input from the broader thrombosis community, the writing group recommends that anticoagulant medications be described by the route of administration and specific targets (e.g., oral factor XIa inhibitor).
Topics: Humans; Anticoagulants; Antithrombins; Blood Coagulation; Thrombosis; Factor Xa Inhibitors; Hemostasis; Atrial Fibrillation; Administration, Oral
PubMed: 36796485
DOI: 10.1016/j.jtha.2023.02.008 -
Thrombosis Research Jul 2022Atrial septal defect, persistent foramen ovale and the left atrial appendage are nowadays often percutaneously closed with implantable devices. These interventions may... (Review)
Review
Atrial septal defect, persistent foramen ovale and the left atrial appendage are nowadays often percutaneously closed with implantable devices. These interventions may be complicated by thromboembolic events and the perfect post-procedural antithrombotic management is still under investigation. The mechanisms leading to left atrial device-related thrombus and thromboembolic complications are not fully understood. Biomarkers of coagulation activation are elevated following percutaneous device placement, peaking within one month and returning to baseline values after three months. By contrast, platelet reactivity shows no post-procedural increase. This suggests that an optimal antithrombotic regimen should perhaps include (oral) anticoagulation therapy rather than the currently more frequently prescribed antiplatelet-based regimen. Furthermore, biomarkers of endothelial activation, fibrinolysis, and on-treatment platelet reactivity may be of value in predicting device-related thrombus and bleeding and guide future medical strategy, facilitating personalized medicine.
Topics: Atrial Appendage; Atrial Fibrillation; Biomarkers; Cardiac Catheterization; Fibrinolytic Agents; Foramen Ovale, Patent; Heart Diseases; Hemostatics; Humans; Retrospective Studies; Septal Occluder Device; Thromboembolism; Thrombosis; Treatment Outcome
PubMed: 35640513
DOI: 10.1016/j.thromres.2022.05.009 -
Circulation Jul 2015Atrial disease or myopathy forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. Current... (Review)
Review
Atrial disease or myopathy forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. Current diagnostic approaches in patients with AF focus on identifying clinical predictors with the evaluation of left atrial size by echocardiography serving as the sole measure specifically evaluating the atrium. Although the atrial substrate underlying AF is likely developing for years before the onset of AF, there is no current evaluation to identify the preclinical atrial myopathy. Atrial fibrosis is 1 component of the atrial substrate that has garnered recent attention based on newer MRI techniques that have been applied to visualize atrial fibrosis in humans with prognostic implications regarding the success of treatment. Advanced ECG signal processing, echocardiographic techniques, and MRI imaging of fibrosis and flow provide up-to-date approaches to evaluate the atrial myopathy underlying AF. Although thromboembolic risk is currently defined by clinical scores, their predictive value is mediocre. Evaluation of stasis via imaging and biomarkers associated with thrombogenesis may provide enhanced approaches to assess risk for stroke in patients with AF. Better delineation of the atrial myopathy that serves as the substrate for AF and thromboembolic complications might improve treatment outcomes. Furthermore, better delineation of the pathophysiologic mechanisms underlying the development of the atrial substrate for AF, particularly in its earlier stages, could help identify blood and imaging biomarkers that could be useful to assess risk for developing new-onset AF and suggest specific pathways that could be targeted for prevention.
Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Electrocardiography; Heart Atria; Humans; Magnetic Resonance Imaging; Muscular Diseases; Risk Factors; Stroke; Thrombosis
PubMed: 26216085
DOI: 10.1161/CIRCULATIONAHA.115.016795