The Effect of Acute Onset Atrial Fibrillation and Rapid Atrial Rates on Markers of Thrombogenesis in the Human Left Atrium

Background: Atrial fibrillation (AF) is associated with thromboembolic stroke. The precise mechanism of thrombogenesis in the human left atrium (LA) with acute AF remains unknown. Methods: 36 AF patients in sinus rhythm undergoing Catheter ablation were studied. Blood samples were taken from the LA and femoral vein immediately after transseptal puncture and 15 minutes after AF induction (14 patients), atrial pacing at 150bpm (14 patients) and in controls (8 patients). Platelet activation (P-selectin), thrombin generation [thrombin-antithrombin (TAT) complex], endothelial dysfunction [asymmetric dimethylarginine(ADMA)] and inflammation [soluble CD40-ligand(sCD40L)] were assessed by flow cytometry and ELISA. Results: P-selectin increased significantly with both AF (14.5±5.8 baseline vs. 22.9 ±12.9%+ve 15min, p>0.01) and pacing (16.2±6.8 baseline vs. 19.5±5.6%+ve 15min, 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 ±25.2pg/L 15min, p>0.01) and pacing (16.5±13.8 baseline vs. 49.0±46.6 pg/L 15min, 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, not seen with pacing (p=ns) or controls (p=ns). Conclusion: Acute onset human AF and rapid atrial rates both result in increased platelet activation and thrombin generation, more pronounced in the human LA. Acute AF also induces endothelial dysfunction and inflammation. These findings suggest that while rapid atrial rates increase the thrombogenic risk, abnormal rhythm further potentiates this risk.