Optimizing Cardiovascular Device Thromboresistance for Eliminating Anticoagulants

描述（由申请人提供）：在我们的I期项目中，该项目由特殊高风险/高影响应用程序资助，成功开发了一种血栓形成预测技术-器械血栓形成模拟器（DTE）-一种用于改善循环心血管器械血栓阻力的通用方法，并证明了其在设计优化中的应用，以实现性能改善。在该Quantum II期项目中，将对来自不同制造商的CVS器械阵列进行测试和优化，最终目标是将其致血栓性降低到使器械接受者无需进行复杂的药理学抗凝治疗的水平。在拟议的quantum项目的第II阶段，DTE将用于优化CVS器械的各个子组的设计：人工心脏瓣膜（PHV）、心室辅助器械（VAD）、双心室VAD和首个FDA批准的临时全人工心脏（TAHt）。所有这些器械都将使用最先进的数值模拟技术在数值域中进行优化，并将与模拟器械内血液动力学的血液动力学剪切器械（HSD）连接-测量器械促进血液凝固的潜力。重复该过程，并将旨在降低器械促凝性的设计修改优化至最终消除使用这些器械所需的风险和复杂抗凝的水平。优化设备的原型将由本提案中的工业合作伙伴制造-其中包括一些已向市场推出几种突破性机械循环支持（MCS）设备的领先公司。优化的原型将由我们在体外测试，以测试DTE优化是否达到其规定的目标，并将在广泛的动物实验系列中进一步在体内测试（在著名的Sarver心脏中心，U。亚利桑那州），以及在各种参与设备制造商的设施。我们将进一步为每个工业合作伙伴建立DTE系统，并对他们进行这种创新方法的培训。我们将与FDA互动，以建立新的器械致血栓性指南。我们的行业合作伙伴将根据器械类型和优化修改的要求，进一步向FDA寻求试验或研究要求（PMA/IDE/HDE），以促进首次人体演示和将优化器械推向市场。据设想，到第二阶段结束时，一些测试和优化的设备将证明消除抗凝治疗的量子进步的潜力。所提供的技术将成为寻求创建，重新设计和测试心血管设备的制造商的重要工具。

DESCRIPTION (provided by applicant): In our Phase I project which was funded under special high-risk/high-impact applications program, a thrombogenicity predictive technology - Device Thrombogenicity Emulator (DTE) - a universal methodology for improving the thromboresistance of circulatory cardiovascular devices was successfully developed, and its application to design optimization for achieving improved performance was demonstrated. In this Quantum Phase II project an array of CVS devices from various manufacturers will be tested and optimized, with the ultimate goal to reduce their thrombogenicity to a level that will liberate the device recipients from the need for complex pharmacological anticoagulation therapy. During the Phase II of the proposed quantum project, the DTE will be utilized to optimize the design of various sub-groups of CVS devices: Prosthetic Heart Valves (PHV), Ventricular Assist Devices (VAD), bi-ventricular VAD, and the first FDA approved temporary Total Artificial Heart (TAHt). All these devices will be optimized in the numerical domain, using cutting edge numerical simulation techniques, and will be interfaced to a Hemodynamic Shearing Device (HSD) that emulates the hemodynamics within the device- in which the potential of the device to promote blood clotting is measured. The process is reiterated, and design modifications aimed at reducing the device thrombogenicity are optimized to a level that will eventually eliminate the use of risky and complex anticoagulation these devices require. Prototypes of optimized devices will be manufactured by the industrial partners in this proposal- among them some of the leading companies who have introduced to the market several break-through mechanical circulatory support (MCS) devices. The optimized prototypes will be tested by us in vitro to test whether the DTE optimization achieved its stated goals, and will be further tested in vivo in an extensive animal experiments series (performed at the renowned Sarver Heart Center, U. Arizona), as well as in the various participating device manufacturers facilities. We will further build DTE systems for each of the industrial partners and train them in this innovative methodology. We will interact with the FDA for establishing new guidelines for device thrombogenicity. Our industrial partners will further seek trial or study requirements from the FDA (PMA/IDE/HDE), as required for the type of device and the optimization modifications, to facilitate first human demonstration and introduction of the optimized devices to the market. It is envisioned that by the end of phase II some of the devices tested and optimized will demonstrate the potential for a quantum advance of eliminating anticoagulation. The technology offered will become an essential tool for manufacturers that seek to create, redesign and test a cardiovascular device.