Optimizing Cardiovascular Devices Thrombogenicity for Eliminating Anticoagulation

描述(由申请人提供)：在这个量子第一阶段项目中，将开发一种用于血液接触式心血管(CVS)设备的血栓形成预测技术。这款创新的设备致血栓仿真器(DTE)将在设备中使用从详细的数值流动建模中提取的应力加载波形，这些波形将被编程到计算机控制的血液动力学剪切设备(HSD)中，该设备能够非常准确地模拟设备的血流动力学，并使用创新的血小板活动状态(PAS)分析来测量致血栓活性。DTE还旨在通过促进在构建原型并在昂贵的临床前/临床试验中进行测试之前测试虚拟设备设计修改来优化设备的血栓形成性能。最终目标是将设备的血栓形成降低到一个水平，使设备接受者从困难的药物抗凝治疗中解脱出来。在拟议的量子项目的第一阶段，将对DTE原型进行测试，以预测CVS设备的子组：人工心脏瓣膜(PHV)和心室辅助设备(VAD)的血栓形成潜力。根据以下具体目标，将测试各种PHV类型和设计，以及脉动VAD模型：将利用最先进的综合数值方法来模拟假体装置中的流动诱导血栓形成，以研究各种人工心脏瓣膜和脉动VAD。这些模型将包括用于研究流动诱导血栓栓塞症的高度分辨的设备几何形状。将绘制和计算可能导致设备血栓形成的“热点”区域。计算机控制的HSD将被测试其在体外复制从数值模拟中提取的导致设备血栓栓塞症的动态应力加载条件的能力。血栓形成潜力将在设备中使用一种创新的、高灵敏的流动诱导血小板止血活性的血小板活性状态(PAS)分析来测量。这些测量将与安装在LVAD系统中的PHV进行的体外PAS测量相关联。DTE(与数值模拟接口的HSD)将作为优化设备的试验台，以将其血栓形成降低到消除对抗凝剂的需求的水平。所提供的技术将成为CVS设备制造商必不可少的研发工具。除了降低研发成本外，它还可以防止因不可接受的血栓形成水平而需要召回设备或停止临床试验的不幸情况，这些情况可能对患者造成灾难性的影响，并给社会和设备制造商带来毁灭性的经济成本。这些节省的资金将转嫁给患者，并有助于降低医疗成本。据设想，它还将通过减少使用抗凝剂进行困难的药理学管理的需要，促进这些设备的长期治疗，这是大多数现有设备的强制要求。

DESCRIPTION (provided by applicant): In this Quantum Phase I project, a thrombogenicity predictive technology for blood contacting cardiovascular (CVS) devices will be developed. This innovative Device Thrombogenicity Emulator (DTE) will use stress loading waveforms extracted from detailed numerical flow modeling in devices that will be programmed into a computer-controlled Hemodynamic Shearing Device (HSD) capable of emulating device hemodynamics with great accuracy, and measure thrombogenicity using an innovative platelet activity state (PAS) assay. The DTE is also aimed at optimizing the thrombogenic performance of devices by facilitating the testing of virtual device design modifications before prototypes are built and tested in costly pre-clinical/clinical trials. The ultimate goal is to reduce device thrombogenicity to a level that will liberate device recipients from the need for difficult pharmacological anticoagulation therapy. During the Phase I of the proposed quantum project, a prototype DTE will be tested for predicting the thrombogenic potential of a sub-group of CVS devices: Prosthetic Heart Valves (PHV) and Ventricular Assist Device (VAD). Various PHV types and designs will be tested, as well as a pulsatile VAD model, according to the following Specific Aims: A state of the art comprehensive numerical methodology for modeling flow induced thrombogenicity in prosthetic devices will be utilized to study various Prosthetic Heart Valves and a pulsatile VAD. The models will include highly resolved device geometries for studying flow-induced thromboembolism. The `hot spot' regions that may lead to device thrombogenicity will be mapped and computed. A computer controlled HSD will be tested for its ability to replicate in vitro the dynamic stress loading conditions leading to device thromboembolism as extracted from the numerical simulations. The thrombogenic potential will be measured in it using an innovative and highly sensitive platelet activity state (PAS) assay of flow induced platelet hemostatic activity in devices. These measurements will be correlated to in-vitro PAS measurements performed with PHV mounted in a LVAD system. The DTE (HSD interfaced with the numerical simulations) will serve as the test-bed for optimizing devices for reducing their thrombogenicity to a level that will eliminate the need for anticoagulants. The technology offered will become an essential R&D tool for CVS devices manufacturers. Besides reducing R&D costs, it may prevent unfortunate situations where devices need to be recalled or clinical trials stopped, because of unacceptable thrombogenicity levels situations that could be catastrophic to patients and with devastating financial costs to society and device manufacturers alike. These savings will be passed on to patients and help in reducing healthcare costs. It is envisioned that it will also facilitate the use of these devices for long term therapy by reducing the need for difficult pharmacological management with anticoagulants, which is mandated for most existing devices.