Effect of Atrial Fibrillation and Increased Atrial Rates on Markers of Left Atrial Thrombogenesis in Humans

Background: Atrial fibrillation (AF) is associated with increased risk of stroke primarily from left atrial thrombus. It is unclear if this is a consequence of the atrial rate or rhythm. Methods: Thirty-six consecutive AF patients presenting in sinus rhythm undergoing catheter ablation were studied. Fourteen patients were induced into AF, 14 patients were atrial paced at 150bpm and eight were controls. Blood samples were taken from the LA and femoral vein immediately after transseptal puncture and 15 minutes after AF induction, atrial pacing and in controls. Platelet activation (P-selectin), thrombin generation [thrombin-antithrombin (TAT) complex], endothelial dysfunction [asymmetric dimethylarginine (ADMA)] and inflammation (sCD40L) were assessed using flow cytometry and ELISA. Results: P-selectin increased significantly with both AF (14.1 ± 5.8 baseline vs. 23.1 ± 13.6% +ve at 15 min, p < 0.01) and pacing (14.8 ± 5.2 baseline vs. 18.4 ± 4.5% +ve 15 min, p < 0.01), but decreased in controls (p < 0.05). TAT increased specifically in the LA with both AF (18.4 ± 16.6 baseline vs. 32.1 ± 25.2 μg/L at 15 min, p < 0.01) and pacing (16.5 ± 13.8 baseline vs. 49.0 ± 46.6 μg/L 15 min, p < 0.01), but decreased peripherally (p < 0.01), and decreased in controls (p < 0.01). With acute AF, ADMA (p < 0.05) and sCD40L (p < 0.01) increased significantly at all sites, not seen with pacing (p = 0.8 ADMA; p = 0.8 sCD40L) or controls (p = 0.3 ADMA; p = 0.5 sCD40L). Conclusion: Acute onset human AF and rapid atrial rates both result in increased platelet activation and thrombin generation. These are most apparent in the LA compared to the systemic circulation. Acute AF also induces endothelial dysfunction and inflammation. These findings suggest that while rapid atrial rates increase the thrombogenic risk, abnormal rhythm may further potentiate this risk.