Optimizing Cardiovascular Device Thromboresistance for Eliminating Anticoagulants

优化心血管装置的抗血栓能力以消除抗凝剂

• 批准号: 8016863
• 负责人: DANNY BLUESTEIN
• 金额: $ 148.64万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8016863
• 关键词: Animal Experiments; Anticoagulants; Anticoagulation; Arizona; Arts; Biological Assay; Bioprosthesis device; Blood Clot; Blood Platelets; Blood coagulation; Cardiovascular system; Clinical; Clinical Trials; Complex; Destinations; Device Designs; Devices; Dipyridamole; FDA approved; Financial cost; Funding; Goals; Guidelines; Health Care Costs; Heart; Heart Valve Prosthesis; Heart failure; Hemostatic Agents; Hot Spot; Human; In Vitro; Instruction; Lead; Life; Liquid substance; Manufacturer Name; Marketing; Measurement; Measures; Mechanics; Methodology; Modeling; Modification; Patients; Performance; Phase; Principal Investigator; Process; Property; Risk; Salicylic Acids; Savings; Series; Societies; Stress; Stroke; Structure; System; Techniques; Technology; Test Result; Testing; Thromboembolism; Training; Ventricular; cost; design; dosage; experience; hemodynamics; high risk; improved; in vivo; innovation; pre-clinical; prevent; programs; prototype; quantum; research and development; simulation; tool; total artificial heart; ventricular assist device

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.

描述（由申请人提供）：在我们的第一阶段项目中，该项目由特殊的高风险/高影响应用计划资助，血栓形成预测技术 - 设备血栓形成模拟器（DTE） - 一种提高循环心血管设备抗血栓能力的通用方法已成功开发，并展示了其在设计优化中的应用，以实现更高的性能。在这个 Quantum II 期项目中，将对来自不同制造商的一系列 CVS 设备进行测试和优化，最终目标是将其血栓形成性降低到一定水平，使设备接受者不再需要复杂的药物抗凝治疗。在拟议量子项目的第二阶段，DTE 将用于优化 CVS 设备各个子组的设计：人工心脏瓣膜 (PHV)、心室辅助设备 (VAD)、双心室 VAD 和第一个FDA 批准了临时人工心脏 (TAHt)。所有这些设备都将使用尖端的数值模拟技术在数值领域进行优化，并将与模拟设备内血流动力学的血流动力学剪切设备 (HSD) 连接，其中设备促进血液凝固的潜力是测量。重复该过程，并优化旨在降低设备血栓形成性的设计修改，最终消除这些设备所需的危险且复杂的抗凝剂的使用。优化设备的原型将由本提案中的工业合作伙伴制造，其中一些领先公司已向市场推出了多种突破性机械循环支持（MCS）设备。我们将在体外对优化后的原型进行测试，以测试 DTE 优化是否实现了其既定目标，并将在广泛的动物实验系列中进一步进行体内测试（在美国亚利桑那州著名的萨弗心脏中心进行），以及就像在各个参与的设备制造商设施中一样。我们将进一步为每个工业合作伙伴构建DTE系统，并用这种创新方法对他们进行培训。我们将与 FDA 互动，制定设备血栓形成的新指南。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展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创建、重新设计和测试心血管设备的制造商的重要工具。 公共卫生相关性：美国每年有超过 500 万患者患有心力衰竭。其中很大一部分人将成为长期机械循环支持（MCS）的候选人。血栓栓塞和随之而来的中风风险仍然是其用于长期目标治疗的关键障碍。 DTE 技术将有助于大幅减少研发和不断增加的医疗成本。消除使用抗凝剂进行困难且昂贵的药物管理有望为使用这些设备作为长期目标治疗并挽救无数生命铺平道路。