Optimizing Cardiovascular Device Thromboresistance for Eliminating Anticoagulants

描述（由申请人提供）：在特殊高风险/高影响应用项目资助的一期项目中，血栓形成预测技术-设备血栓形成模拟器(DTE) -一种用于改善循环心血管设备血栓抵抗的通用方法被成功开发，并证明了其应用于设计优化以实现改进性能。在这个Quantum II期项目中，来自不同制造商的CVS设备阵列将被测试和优化，其最终目标是将其致血栓性降低到一定水平，从而将设备接受者从复杂的药物抗凝治疗中解放出来。在拟议的量子项目的第二阶段，DTE将用于优化CVS设备的各个子组的设计：假心脏瓣膜（PHV），心室辅助装置（VAD），双心室VAD和第一个FDA批准的临时全人工心脏（TAHt）。所有这些设备都将在数值领域进行优化，使用尖端的数值模拟技术，并将连接到模拟设备内血液动力学的血流动力学剪切装置（HSD），其中测量设备促进血液凝固的潜力。该过程反复进行，旨在降低设备血栓形成性的设计修改被优化到一个水平，最终将消除使用这些设备所需的危险和复杂的抗凝。优化设备的原型将由本提案中的工业合作伙伴制造-其中一些领先的公司已经向市场推出了几个突破性的机械循环支持（MCS）设备。优化的原型将由我们在体外测试，以测试DTE优化是否达到其既定目标，并将在广泛的动物实验系列中进一步进行体内测试（在著名的Sarver心脏中心进行），以及在各种参与设备制造商的设施中。我们将进一步为每个工业合作伙伴建立DTE系统，并用这种创新方法培训他们。我们将与FDA合作制定器械致血栓性的新指南。我们的工业合作伙伴将根据设备类型和优化修改的要求，进一步寻求FDA （PMA/IDE/HDE）的试验或研究要求，以促进首次人体演示并将优化的设备引入市场。预计到第二阶段结束时，一些经过测试和优化的设备将显示出消除抗凝的量子进步的潜力。所提供的技术将成为寻求制造、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. PUBLIC HEALTH RELEVANCE: Over 5 million patients in the US suffer annually from heart failure. Of those a significant proportion will become candidates for longer-term mechanical circulatory support (MCS). Thromboembolism and the attendant risk for stroke remains the critical barrier to their use for long term destination therapy. The DTE technology will help in drastically reducing the R&D and escalating healthcare costs involved. Elimination of difficult and costly pharmacological management with anticoagulants is expected to pave the way for the use of these devices as long term destination therapy and save countless lives.