A comprehensive testing platform for mechanical heart valves to propel innovation towards anticoagulant-independence

机械心脏瓣膜的综合测试平台，推动创新走向抗凝独立性

• 批准号: 10592424
• 负责人: Alessandro Bellofiore
• 金额: $ 25.64万
• 依托单位: SAN JOSE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-20 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592424
• 关键词: Address; Adult; Adverse effects; Affect; Age; Anticoagulant therapy; Anticoagulants; Artificial Heart; Bioprosthesis device; Blood; Blood Circulation; Blood Platelets; Blood coagulation; Blood flow; Characteristics; Child; Childhood; Circulation; Clinical; Coagulation Process; Communities; Dependence; Deposition; Developing Countries; Education; Environment Design; Exhibits; Exposure to; FDA approved; Future; Generations; Goals; Growth; Guidelines; Heart Valves; Image; In Vitro; Lasers; Life; Measurement; Measures; Mechanics; Optics; Outcome; Patients; Performance; Platelet Activation; Play; Population; Prognosis; Recommendation; Recording of previous events; Repeat Surgery; Research; Rest; Role; Students; Surface; Testing; Thromboembolism; Thrombus; Time; Velocimetries; Work; analog; aortic valve disorder; aortic valve replacement; blood damage; design; graduate student; health care availability; hemodynamics; implantation; improved; in vivo; indexing; innovation; low income country; mechanical load; novel; older patient; particle; pediatric patients; performance tests; prototype; shear stress; thrombogenesis; thrombotic; time use; treatment strategy; undergraduate student; underrepresented minority student; young adult

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.

项目摘要 需要置换主动脉瓣的患者面临机械心脏瓣膜（MHV）之间的选择 和生物假体阀。对于年轻患者，MHV由于其极高的耐用性而优选，但 他们在余生中依赖抗凝治疗。强烈需要火花 停滞的MHV设计的创新，该设计在40年内没有实质性变化。最终目标 是为了迎接新一代的MHV，这些MHV完全独立于抗凝剂。 PL的 长期目标是为设计创建和维持一个以学生为中心的研究环境， 新型MHV设计范例的原型和测试，这些范例可改善瓣膜血液动力学性能和 降低血栓形成。大量工作已经阐明了异常流动的重要性 在铰链附近和MHV闭合附近触发血小板激活，从而引发血小板激活的特征。到 进一步提高对流动诱导的血液凝结的理解，并识别无抗凝剂的MHV设计， PI将开发一个MHV测试平台，该平台解释了凝块沉积对附近血流的影响 MHV并允许在两种血液动力学测试 （需要光学清晰的血液类似物）和血栓形成测试（需要真实的血液）。实现 这是PI将结合基于激光的流量测量和前所未有的流体动力测试仪 MHV血栓形成测试仪基于pumpless闭环中MHV的血液循环。 这项研究的基本假设是，与用于体外和数值的原始MHV不同 研究，凝块在体内发生的MHV上的沉积显着影响血流特征， 血小板的机械负载和血栓生长速率。未来的MHV设计策略应考虑 MHV植入后发生的基本血流动力学变化。这项研究的具体目的是： 目标1。量化凝块沉积范围，剪切应力和血小板损伤指数之间的关系。 AIM 2。与Bileaflet MHV相比，研究三叶型MHV的血液动力学和血栓形成性。 AIM 3。量化阀尺寸对MHV中阀门闭合附近流速和剪切应力的影响。 该项目将（1）建立一个准确的平台，用于全面的MHV血液动力学/血栓形成性 测试将推动主动脉瓣疾病治疗的创新； （2）演示角色 沉积物在血栓生长中发挥作用； （3）演示成人和小儿三叶型MHV的生存能力 人群。这些结果为未来的无抗凝物MHV进行研究奠定了基础。 改变了发展中国家的年轻患者和患者的治疗选择和预后。为了 参与的研究生和本科生，包括来自代表性不足的少数民族的学生， 项目是一个独特的研究和教育机会，可以专业地丰富他们并增加他们的 吸引潜在的招聘人员。