Effect of atrial fibrillation on atrial thrombogenesis in humans: impact of rate and rhythm
Open accessAbstract
Objectives We sought to assess the effect of atrial fibrillation (AF) on atrial thrombogenesis in humans by determining the impact of rate and rhythm.Background Although AF is known to increase the risk of thromboembolic stroke from the left atrium (LA), the exact mechanisms remain poorly understood.Methods We studied 55 patients with AF who underwent catheter ablation while in sinus rhythm; 20 patients were induced into AF, 20 patients were atrial paced at 150 beats/min, and 15 were control patients. Blood samples were taken from the LA, right atrium, and femoral vein at baseline and at 15 min in all 3 groups. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay.Results Platelet activation increased significantly in both the AF (p < 0.001) and pacing (p < 0.05) groups, but decreased in control patients (p < 0.001). Thrombin generation increased specifically in the LA compared with the periphery in both the AF (p < 0.01) and pacing (p < 0.01) groups, but decreased in control patients (p < 0.001). With AF, ADMA (p < 0.01) and sCD40L (p < 0.001) levels increased significantly at all sites, but were unchanged with pacing (ADMA, p = 0.5; sCD40L, p = 0.8) or in control patients (ADMA, p = 0.6; sCD40L, p = 0.9).Conclusions Rapid atrial rates and AF in humans both result in increased platelet activation and thrombin generation. Prothrombotic activation occurs to a greater extent in the human LA compared with systemic circulation. AF additionally induces endothelial dysfunction and inflammation. These findings suggest that although rapid atrial rates increase the thrombogenic risk, AF may further potentiate this risk.
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Even short episodes of AF lead to myocardial damage and expression of prothrombotic factors on the atrial endothelial surface, and activation of platelets and inflammatory cells, and contribute to a generalized prothrombotic state.
“Furthermore, even short episodes of AF lead to myocardial damage and expression of prothrombotic factors on the atrial endothelial surface, and activation of platelets and inflammatory cells, and contribute to a generalized prothrombotic state.88,89”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [88]
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
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- Authors
- Lim, H. S., Willoughby, S. R., Schultz, C., Gan, C., Alasady, M., Lau, D. H., Leong, D. P., Brooks, A. G., Young, G. D., Kistler, P. M., Kalman, J. M., Worthley, M. I., & Sanders, P.
- Affiliations
- Royal Adelaide Hospital (AU)
- Baker Heart and Diabetes Institute (AU)
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Sanders, Prashanthan
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 61
- Issue
- 8
- Pages
- 852-860
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2152638483
- Cited by
- 199
- References
- 46
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 11 · 2022: 13 · 2021: 16 · 2020: 9 · 2019: 10 · 2018: 19 · 2017: 21 · 2016: 28 · 2015: 25 · 2014: 16 · 2013: 18
- FWCI
- 19.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- Boston Scientific Corporation
- Medtronic
- National Health and Medical Research Council
- St. Jude Medical
- National Heart Foundation of Australia
- Merck
- University of Adelaide
- Sanofi
- Biotronik
- Biosense Webster
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Keywords
- atrial fibrillation, atrial pacing, atrial rate, left atrium, platelet activation, thrombin generation, endothelial dysfunction, asymmetric dimethylarginine, soluble CD40 ligand, inflammation, thromboembolic stroke
- MeSH terms
- Aged, Antithrombin III, Arginine, Atrial Fibrillation, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Female, Heart Atria, Heart Rate, Humans, Male, Middle Aged, Peptide Hydrolases, Risk Factors, Statistics as Topic, Thrombosis, Platelet Activation, Catheter Ablation, Risk Assessment, P-Selectin, Stroke, CD40 Ligand
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