CAREER: The Role of Geometric and Structural Heterogeneity on Heart Left Atrium Blood-Clot Dynamics

About This Grant

This Faculty Early Career Development (CAREER) award will support research that intends to advance understanding of the blood-clot interactions that may result in stroke for some patients with heart rhythm disorders. Atrial fibrillation, the irregular beating of the heart’s left atrium, is the most common heart rhythm disorder affecting millions of people worldwide. This condition leads to a four to five-fold increase in stroke risk. More than 90% of the blood clots that result in stroke are confined to the left atrial appendage due to low blood velocities in this region of the heart. However, there is a gap in our understanding of how the differences in left atrial geometry and tissue structure contribute to clot growth and clot breakup that can lead to stroke. This project will create a computational model of the left atrium to investigate how the heart’s structure changes blood flow patterns, elevating the risk of clot breakup. The knowledge gained from this project could have a far-reaching impact on other applications where clotting is a major risk, such as deep vein thrombosis and prosthetic heart valves. Further, this research will be integrated into an educational program and outreach plan under the theme of Engineering for Cardiovascular Health and Wellness. This includes enhanced coursework with hands-on projects and on-site and virtual research opportunities. These activities are designed to promote interest in STEM careers while fostering awareness of heart disease and biomechanics research. The research goals of this project are (i) to understand how the left atrial geometric and structural characteristics correlate with arrhythmogenic contraction and thrombogenic blood flow pattern and (ii) to interrogate how the left atrial tissue-blood interactions destabilize a clot to embolize, thereby leading to stroke. These goals intend to be met by creating an enhanced multiphysics cardiac biomechanics modeling framework capturing coagulation cascade and blood-clot interactions. Specific research objectives include (1) to create arrhythmogenic excitation-contraction patterns by varying the left atrial geometric and structural parameters, including size, tissue thickness, pulmonary vein attachments, and the extent of tissue fibrosis, (2) to evaluate the thrombogenicity of aberrant wall motions triggered due to atrial fibrillation, and (3) to understand blood-clot interactions in the setting of a deforming left atrial appendage. Critical questions to be answered include: (a) Do all atrial fibrillations trigger clots? (b) Is the clot severity associated with geometric hotspots and structural remodeling patterns? (c) What hemodynamic mechanisms are responsible for clot fragmentation and dissociation into emboli? These research activities are integrated into an educational and outreach plan that expands accessibility in engineering education. Together, the project supports the PI’s long-term goal to advance the clinical management of heart disease through cardiovascular biomechanics research while providing multidisciplinary education to a new generation of students. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.