Effect of atrial fibrillation on atrial thrombogenesis in humans: Impact of rate and rhythm

Han S. Lim, Scott R. Willoughby, Carlee Schultz, Cheryl Gan, Muayad Alasady, Dennis H. Lau, Darryl P. Leong, Anthony G. Brooks, Glenn D. Young, Peter M. Kistler, Jonathan M. Kalman, Matthew I. Worthley, Prashanthan Sanders

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages852-860
Number of pages9
JournalJournal of the American College of Cardiology
Volume61
Issue number8
DOIs
Publication statusPublished - 26 Feb 2013

Keywords

  • atrial fibrillation
  • atrium
  • stroke
  • thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lim, H. S., Willoughby, S. R., Schultz, C., Gan, C., Alasady, M., Lau, D. H., ... Sanders, P. (2013). Effect of atrial fibrillation on atrial thrombogenesis in humans: Impact of rate and rhythm. Journal of the American College of Cardiology, 61(8), 852-860. https://doi.org/10.1016/j.jacc.2012.11.046
Lim, Han S. ; Willoughby, Scott R. ; Schultz, Carlee ; Gan, Cheryl ; Alasady, Muayad ; Lau, Dennis H. ; Leong, Darryl P. ; Brooks, Anthony G. ; Young, Glenn D. ; Kistler, Peter M. ; Kalman, Jonathan M. ; Worthley, Matthew I. ; Sanders, Prashanthan. / Effect of atrial fibrillation on atrial thrombogenesis in humans : Impact of rate and rhythm. In: Journal of the American College of Cardiology. 2013 ; Vol. 61, No. 8. pp. 852-860.
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abstract = "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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Lim, HS, Willoughby, SR, Schultz, C, Gan, C, Alasady, M, Lau, DH, Leong, DP, Brooks, AG, Young, GD, Kistler, PM, Kalman, JM, Worthley, MI & Sanders, P 2013, 'Effect of atrial fibrillation on atrial thrombogenesis in humans: Impact of rate and rhythm', Journal of the American College of Cardiology, vol. 61, no. 8, pp. 852-860. https://doi.org/10.1016/j.jacc.2012.11.046

Effect of atrial fibrillation on atrial thrombogenesis in humans : Impact of rate and rhythm. / Lim, Han S.; Willoughby, Scott R.; Schultz, Carlee; Gan, Cheryl; Alasady, Muayad; Lau, Dennis H.; Leong, Darryl P.; Brooks, Anthony G.; Young, Glenn D.; Kistler, Peter M.; Kalman, Jonathan M.; Worthley, Matthew I.; Sanders, Prashanthan.

In: Journal of the American College of Cardiology, Vol. 61, No. 8, 26.02.2013, p. 852-860.

Research output: Contribution to journalArticle

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T1 - Effect of atrial fibrillation on atrial thrombogenesis in humans

T2 - Journal of the American College of Cardiology

AU - Lim, Han S.

AU - Willoughby, Scott R.

AU - Schultz, Carlee

AU - Gan, Cheryl

AU - Alasady, Muayad

AU - Lau, Dennis H.

AU - Leong, Darryl P.

AU - Brooks, Anthony G.

AU - Young, Glenn D.

AU - Kistler, Peter M.

AU - Kalman, Jonathan M.

AU - Worthley, Matthew I.

AU - Sanders, Prashanthan

PY - 2013/2/26

Y1 - 2013/2/26

N2 - 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.

AB - 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.

KW - atrial fibrillation

KW - atrium

KW - stroke

KW - thrombosis

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DO - 10.1016/j.jacc.2012.11.046

M3 - Article

VL - 61

SP - 852

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JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

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