Rapid Atrial Rates and Atrio-Ventricular Dyssynchrony Predispose to Increased Thrombogenesis in the Human Left Atrium in Patients with Atrial Fibrillation

Background: Atrial fibrillation (AF) is associated with increased thromboembolic stroke risk. The effect of rapid atrial rates on thrombogenesis in the human left atrium (LA) remains unknown. Methods: Twelve patients with AF undergoing catheter ablation in sinus rhythm (SR) and eight with supraventricular tachycardia (SVT) due to left-sided accessory pathways were studied with rapid atrial pacing at 150 bpm. Eight patients with AF in SR served as controls. Blood was sampled from the LA, right atrium (RA) and femoral vein (FV) at baseline and 15 min after pacing or in controls. Platelet activation (platelet P-selectin), thrombin generation [thrombin–antithrombin-complex (TAT)] endothelial dysfunction [asymmetric dimethylarginine (ADMA)] and platelet-derived inflammation [soluble-CD40-ligand (sCD40L)] were measured by flow cytometry and ELISA. Results: With rapid atrial pacing, thrombin generation increased significantly in the AF group (log TAT 1.29 ± 0.56 mcg/L at 15 min vs. 1.05 ± 0.34 at baseline; p < 0.01), specifically in the LA and RA compared to the FV. This was markedly observed in patients with AV dyssynchrony (p < 0.01). In contrast, thrombin generation decreased in the SVT group (p < 0.01) and control group (p < 0.01). Platelet activation increased in AF patients with pacing (log P-selectin 1.27 ± 0.10% vs. 1.14 ± 0.17%; p < 0.01), was unchanged in the SVT group (p = 0.8) and decreased in controls (p < 0.01). ADMA and sCD40L were unchanged in all three groups. Conclusion: Rapid atrial rates increase LA thrombin generation and platelet activation in patients with AF. This effect is accentuated with AV dyssynchrony. However, rapid atrial rates did not result in abnormal markers in SVT patients, suggesting the additional role of abnormal substrate in AF patients.