Modelling Blood Flow and Biochemical Reactions Underlying Thrombogenesis in Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is a widespread cardiac disease associated with a high risk of thromboembolic stroke. Clinically applicable stroke-risk stratification schemes can be improved with a mechanistic understanding of the underlying thrombogenicity induced by AF – blood stasis, hypercoagulability and endothelial damage – known as Virchow’s triad. We propose a coupled biophysical modelling scheme which integrates all aspects of Virchow’s triad using computational fluid dynamics (CFD) to represent blood stasis, reaction–diffusion-convection equations for the blood coagulation cascade and the endothelial cell activation potential (ECAP) to quantify endothelial damage. This comprehensive workflow is tested on a 3D patient-specific geometry reproduced from cardiac Cine MRI data. The patient case was tested in both AF and regular sinus rhythm (SR) conditions with two thrombus initiation sites: i) peak ECAP in the LA appendage (LAA) and ii) positioned at the LAA tip, totalling four cases (A-D). Case A (SR and peak ECAP initiation) washed out all thrombogenic proteins after one cardiac cycle showing low risk of thrombus formation. Case D (AF and LAA tip initiation) led to unregulated clot formation, solidification and storage in the LAA. This finding suggests that the solidified thrombus may be ejected from the LAA and travel towards the brain if the patient reverted to SR. This novel pipeline provides a promising tool that can be extended to larger patient cohorts.