Optimizing Cardiovascular Devices Thrombogenicity for Eliminating Anticoagulation

描述（由申请人提供）：在这个量子一期项目中，将开发血液接触心血管（CVS）设备的血栓形成性预测技术。这种创新的设备血栓形成模拟器（DTE）将使用从设备中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流动力学剪切装置（HSD）中，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性状态（PAS）测定来测量血栓形成性。DTE还旨在通过促进虚拟设备设计修改的测试，在原型构建和昂贵的临床前/临床试验中进行测试之前，优化设备的血栓形成性能。最终目标是将器械的血栓形成性降低到一定水平，从而使器械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，将测试一个原型DTE，以预测CVS设备亚组的血栓形成潜力：假肢心脏瓣膜（PHV）和心室辅助装置（VAD）。根据以下具体目标，将测试各种PHV类型和设计，以及脉动性VAD模型：将利用最先进的模拟假体装置中血流诱导血栓性的综合数值方法来研究各种假体心脏瓣膜和脉动性VAD。该模型将包括用于研究血流诱发血栓栓塞的高分辨率设备几何形状。可能导致器械血栓形成的“热点”区域将被绘制和计算。计算机控制的HSD将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的动态应力加载条件的能力。血栓形成的潜力将使用创新和高度敏感的血小板活性状态（PAS）测定装置中血流诱导血小板止血活性来测量。这些测量将与在LVAD系统中安装PHV进行的体外PAS测量相关联。DTE （HSD与数值模拟接口）将作为优化设备的试验台，以降低其血栓形成性，从而消除对抗凝血剂的需求。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，它还可以防止因血栓形成程度不可接受而需要召回设备或停止临床试验的不幸情况，这种情况可能对患者造成灾难性后果，并给社会和设备制造商带来毁灭性的财务成本。这些节省下来的费用将转嫁给患者，并有助于降低医疗成本。预计它还将通过减少对抗凝药物的困难药理学管理的需要，促进这些设备在长期治疗中的使用，这是大多数现有设备所强制要求的。

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.