Project Summary Patients needing aortic valve replacement are faced with a choice between mechanical heart valves (MHVs) and bioprosthetic valves. For younger patients, MHVs are preferable because of their extreme durability, but they become dependent on anticoagulant therapy for the rest of their life. There is a strong need to spark innovation over the stagnant MHV design, which has not substantially changed in 40 years. The ultimate goal is to usher in a new generation of MHVs that achieve complete independence from anticoagulants. The Pl's long-term objective is to create and sustain a student-centered research environment for the design, prototyping and testing of novel MHV design paradigms that improve valve hemodynamic performance and reduce thrombogenicity. A substantial amount of work has already elucidated the importance of abnormal flow features in triggering platelet activation, and thus blood clotting, near the hinges and the closing of MHVs. To further advance the understanding of flow-induced blood clotting and identify anticoagulant-free MHV designs, the PI will develop a MHV testing platform that accounts for the effect of clot deposits on blood flow near the MHV and allows to reproduce comparable realistic flow conditions for both hemodynamic performance tests (which require an optically-clear blood analog) and thrombogenicity tests (which require real blood). To achieve that, the PI will combine a hydrodynamic tester for laser-based flow measurements and an unprecedented MHV thrombogenicity tester based on blood circulation through MHVs in a pumpless closed loop. The underlying hypothesis of this research is that, unlike with the pristine MHVs used for in-vitro and numerical studies, the deposition of clot on the MHV that occurs in-vivo significantly affects blood flow features, mechanical loading of platelets, and thrombus growth rate. Future MHV design strategies should consider the fundamental hemodynamic changes occurring after MHV implantation. The specific aims of this study are: Aim 1. Quantify the relationship between clot deposit extent, shear stress and platelet damage indices. Aim 2. Investigate hemodynamics and thrombogenicity of trileaflet MHVs, compared to bileaflet MHVs. Aim 3. Quantify the effect of valve size on flow velocities and shear stress near valve closure in MHVs. This project will (1) establish an accurate platform for comprehensive MHV hemodynamics/thrombogenicity testing that will propel innovation in the treatment of aortic valve disease; (2) demonstrate the role thrombus deposits play in thrombus growth; (3) demonstrate the viability of trileaflet MHVs for adult and pediatric populations. These outcomes lay the ground work for future research on anticoagulant-free MHVs that will transform treatment options and prognosis for younger patients and patients from developing countries. For the graduate and undergraduate students involved, including students from underrepresented minorities, this project is a unique research and educational opportunity that will enrich them professionally and increase their appeal to potential recruiters.

Project Narrative Clinical guidelines for aortic valve replacement recommend mechanical heart valves for younger patients (≤ 60 years old) and patients who cannot undergo multiple reoperations. To alleviate the need for these patients to take anticoagulants daily for the rest of their life, the design of mechanical heart valves must be innovated to improve hemodynamic performance, thus reducing their thrombogenicity. We propose to develop a novel experimental platform that will allow for better understanding of MHV flow-induced blood clotting mechanisms and comprehensive testing of new design paradigms to achieve independence from anticoagulants.