Effect of Atrial Fibrillation on Atrial Thrombogenesis in Humans: Impact of Rate and Rhythm

被引:158
|
作者
Lim, Han S. [1 ,2 ]
Willoughby, Scott R. [1 ,2 ]
Schultz, Carlee [1 ,2 ]
Gan, Cheryl [1 ,2 ]
Alasady, Muayad [1 ,2 ]
Lau, Dennis H. [1 ,2 ]
Leong, Darryl P. [1 ,2 ]
Brooks, Anthony G. [1 ]
Young, Glenn D. [1 ,2 ]
Kistler, Peter M. [3 ]
Kalman, Jonathan M. [4 ,5 ]
Worthley, Matthew I. [1 ,2 ]
Sanders, Prashanthan [1 ,2 ]
机构
[1] Univ Adelaide, Ctr Heart Rhythm Disorders, Adelaide, SA, Australia
[2] Royal Adelaide Hosp, Adelaide, SA 5000, Australia
[3] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia
[4] Royal Melbourne Hosp, Dept Cardiol, Melbourne, Vic, Australia
[5] Univ Melbourne, Dept Med, Melbourne, Vic, Australia
基金
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词
atrial fibrillation; atrium; stroke; thrombosis; C-REACTIVE PROTEIN; PLATELET ACTIVATION; P-SELECTIN; ENDOTHELIAL DYSFUNCTION; NITRIC-OXIDE; ASYMMETRICAL DIMETHYLARGININE; INCREASED EXPRESSION; SINUS RHYTHM; CD40; LIGAND; MECHANISMS;
D O I
10.1016/j.jacc.2012.11.046
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (J Am Coll Cardiol 2013;61:852-60) (c) 2013 by the American College of Cardiology Foundation
引用
收藏
页码:852 / 860
页数:9
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