Basic/Translational Science -> Whole Animal Electrophysiology and Pharmacology (includes Neurohumoral Modulation) D-PO05 - Poster Session V (ID 39) Poster

D-PO05-059 - Rivaroxaban Treatment In An Atrial Fibrillation Goat Model Protects Against Atrial Myocyte Hypertrophy, But Does Not Affect Af Complexity During 4 Months Of Persistent Atrial Fibrillation (ID 528)


Background: Atrial fibrillation (AF) is associated with hypercoagulability. In turn, hypercoagulability can contribute to AF complexity by affecting the AF substrate. Coagulation factors (e.g. FXa) can activate protease-activated receptors (PARs) involved in pathophysiological remodeling processes. Rivaroxaban, a FXa-inhibitor, might protect the heart against PAR-mediated remodeling during AF.
Objective: To evaluate FXa-inhibition on AF-induced atrial remodeling in a goat model.
Methods: Three groups were studied; A. sham goats without AF (n=10), B. goats with 4-months AF (n=10) and C. goats with 4 months AF treated with rivaroxaban (n=11). AF was electrically maintained for 16 weeks. Rivaroxaban treatment was targeted at a plasma concentration of >25ng/ml. Coagulation activity was analyzed using tissue factor induced thrombin generation assays. AF cardioversion attempts with flecainide were undertaken at max. 4 different time points: 3, 5, 10 and 15weeks of AF. A final experiment consisted of hemodynamic measurements and atrial mapping using a 249-channel electrode array to study complexity of conduction patterns, quantified as waves/cycle and fractionation index. Atrial tissue samples were collected for histological and genetic analysis.
Results: The average rivaroxaban plasma concentration was 54.16ng/ml. Thrombin generation did not differ between sham and AF, but was about 3-fold decreased in the rivaroxaban goats. Atrial myocyte hypertrophy was present after 4 months of AF (AF vs. sham, p<0.05) and was fully prevented in rivaroxaban goats (AF vs. rivaroxaban, p<0.01). Left atrial mapping analysis demonstrated an increase in AF complexity after 4 months of AF, which was not prevented by rivaroxaban treatment. Additionally, hemodynamics did not differ between AF and rivaroxaban goats, nor did relative heart weights between any of the groups. AF stability at 3 weeks AF tended to be higher in AF- compared to rivaroxaban goats, but not at later time points. Preliminary analysis of left atrial gene expression showed increased BNP mRNA levels after 4 months of AF, which tended to be attenuated by rivaroxaban treatment.
Conclusion: Rivaroxaban treatment prevented myocyte hypertrophy after 4 months of AF, but did not affect AF complexity or stability.