Development and Preclinical Testing of the TORVAD Ventricular Assist System in Preparation for First in Human Implantation

 描述(申请人提供)：TORVAD(Tm)是一种独特的心室辅助系统，可提供低剪切、同步、脉动的血流。由于活塞的速度相对较低，泵抽引起的血液剪切最小，活塞由流体动力轴承支撑，旨在保持活塞和环形壁之间的固定间隙。TORVAD与心脏同步，以保护主动脉瓣血流，并通过Frank-Starling机制维持心输出量的自动调节。TORVAD的设计还允许固有地确定泵的差压，而不需要额外的传感器，可用于管理患者的药物和泵的流量。这些优势已在初步研究中得到证实。体外试验表明，与临床上可用的连续流动装置相比，低剪切设计保留了高分子量的von Willebrand因子，并显著减少了溶血。TORVAD的血液学结果是任何其他脑室辅助设备无法比拟的。此外，同步血流动力学已在急性和慢性动物模型中得到证实。这些初步发现表明，TORVAD有可能减少与使用其他脑室辅助装置相关的出血、血栓形成和中风。该项目的目标是通过进行必要的验证和确认步骤，将TORVAD从研发过渡到首个人类临床试验，以确定TORVAD系统的安全性，并为早期可行性研究申请研究设备豁免(IDE)。这将完成如下工作：1)利用以前的原型经验完成设计，实施设计控制，并对系统进行风险分析；2)制造和组装35个系统进行测试；3)进行子系统验证测试；4)完成体外设计评估和系统性能测试，以确认设备的性能和可靠性；5)进行体内急性和慢性动物实验，以证明设备的安全性；6)申请集成开发环境进行早期可行性研究。

 DESCRIPTION (provided by applicant): The TORVAD(tm) is a unique ventricular assist system that delivers low-shear, synchronous, pulsatile flow. Blood shear due to pumping is minimized by the relatively low speed of pistons supported by hydrodynamic bearings designed to maintain a fixed gap between the piston and torus walls. The TORVAD synchronizes with the heart to preserve aortic valve flow and maintains autoregulation of cardiac output by the Frank-Starling mechanism. The design of the TORVAD also allows for inherent determination of differential pump pressure, without additional sensors, which can be used to manage patient medications and pump flow rates. These advantages have been confirmed in preliminary studies. In vitro tests have demonstrated that the low-shear design preserves high-molecular-weight von Willebrand factor and results in significantly reduced hemolysis as compared to clinically available continuous flow devices. The TORVAD's hematological results are unmatched by any other ventricular assist device. In addition, synchronous hemodynamics have been demonstrated using acute and chronic animal models. These preliminary findings demonstrate that the TORVAD has the potential to reduce bleeding, thrombus formation, and strokes that are associated with the use of other ventricular assist devices. The goal of this project is to bridge the TORVAD from R&D to first-in-human clinical trials by conducting the verification and validation steps necessary to determine the safety of the TORVAD system and to apply for an Investigational Device Exemption (IDE) for an Early Feasibility Study. This will be accomplished as follows: 1) Use previous experience with prototypes to finalize the design, implement design controls, and perform risk analysis on the system; 2) Fabricate and assemble 35 systems for testing; 3) Perform subsystem verification testing; 4) Complete in vitro design evaluation and system performance testing to confirm device performance and reliability; 5) Conduct in vivo acute and chronic animal experiments to demonstrate device safety; and 6) Apply for an IDE for an early feasibility study.