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: 10379306
• 负责人: Alessandro Bellofiore
• 金额: $ 29.3万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10379306
• 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; Clinical; Coagulation Process; Communities; Dependence; Deposition; Developing Countries; 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; Recording of previous events; Repeat Surgery; Research; Rest; Role; Students; Surface; Testing; Thrombus; Time; Velocimetries; Work; analog; aortic valve disorder; aortic valve replacement; base; blood damage; design; graduate student; health care availability; hemodynamics; implantation; improved; in vivo; indexing; innovation; low income country; mechanical load; novel; 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.

项目概要 需要主动脉瓣置换术的患者面临着机械心脏瓣膜 (MHV) 之间的选择 和生物瓣膜。对于年轻患者来说，MHV 更可取，因为它们具有极高的耐用性，但是 他们终生依赖抗凝治疗。有强烈的火花需求 对停滞不前的 MHV 设计进行创新，该设计 40 年来没有发生实质性变化。最终目标 的目标是引入新一代 MHV，使其完全独立于抗凝剂。 PL的 长期目标是创建和维持以学生为中心的设计研究环境， 新型 MHV 设计范例的原型设计和测试，可改善瓣膜血流动力学性能和 减少血栓形成。大量工作已经阐明了异常流量的重要性 其特点是触发血小板活化，从而在铰链附近发生血液凝固并关闭 MHV。到 进一步加深对血流诱导血液凝固的理解并确定无抗凝剂的 MHV 设计， PI 将开发一个 MHV 测试平台，该平台可以解释凝块沉积物对血管附近血流的影响 MHV 并允许为血流动力学性能测试重现可比的真实流量条件 （需要光学透明的血液类似物）和血栓形成测试（需要真实的血液）。达到 PI 将结合用于基于激光的流量测量的水动力测试仪和前所未有的 MHV 血栓形成测试仪基于无泵闭环中 MHV 的血液循环。 这项研究的基本假设是，与用于体外和数值模拟的原始 MHV 不同， 研究表明，体内发生的 MHV 上的凝块沉积会显着影响血流特征， 血小板的机械负荷和血栓生长速率。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。本研究的具体目的是： 目标 1. 量化凝块沉积程度、剪切应力和血小板损伤指数之间的关系。 目标 2. 研究三叶 MHV 与双叶 MHV 的血流动力学和血栓形成性。 目标 3. 量化 MHV 中阀门尺寸对阀门关闭附近的流速和剪切应力的影响。 该项目将 (1) 建立一个准确的综合 MHV 血流动力学/血栓形成平台 推动主动脉瓣疾病治疗创新的测试； (2) 演示血栓的作用 沉积物促进血栓生长； (3) 证明三叶 MHV 对成人和儿童的可行性 人口。这些结果为未来无抗凝剂 MHV 的研究奠定了基础， 改变年轻患者和发展中国家患者的治疗选择和预后。对于 参与的研究生和本科生，包括来自代表性不足的少数族裔的学生，这 项目是一个独特的研究和教育机会，将丰富他们的专业知识并提高他们的能力 对潜在的招聘人员有吸引力。