Optimizing Cardiovascular Devices Thrombogenicity for Eliminating Anticoagulation

描述（由申请人提供）：在本Quantum I期项目中，将开发血液接触心血管（CVS）器械的促凝性预测技术。这一创新性器械促凝性模拟器（DTE）将使用从器械中的详细数值流模型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器械（HSD）中，该器械能够非常准确地模拟器械血液动力学，并使用创新的血小板活性状态（PAS）测定法测量促凝性。DTE还旨在通过在构建原型并在昂贵的临床前/临床试验中进行测试之前促进虚拟器械设计修改的测试来优化器械的血栓形成性能。最终目标是将器械致血栓性降低到一定水平，使器械接受者无需进行困难的药理学抗凝治疗。在拟议量子项目的第一阶段，将对原型DTE进行测试，以预测CVS器械亚组的血栓形成潜力：人工心脏瓣膜（PHV）和心室辅助器械（VAD）。根据以下特定目的，将对各种PHV类型和设计以及脉动式VAD模型进行试验：将利用模拟人工器械中流动诱导血栓形成的最新综合数值方法研究各种人工心脏瓣膜和脉动式VAD。模型将包括用于研究流动诱导血栓栓塞的高分辨率器械几何形状。将绘制并计算可能导致器械血栓形成的"热点"区域。将测试计算机控制的HSD在体外复制从数值模拟中提取的导致器械血栓栓塞的动态应力加载条件的能力。将使用创新的高灵敏度血小板活性状态（PAS）测定装置中的流动诱导血小板止血活性来测量其血栓形成潜力。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。DTE（与数值模拟接口的HSD）将作为优化器械的试验台，以将其血栓形成性降低到无需抗凝剂的水平。 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，它还可以防止由于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。这些节省的费用将转嫁给患者，并有助于降低医疗成本。据设想，它还将通过减少对使用抗凝剂的困难药理学管理的需求来促进这些器械用于长期治疗，这是大多数现有器械的强制要求。

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.