Advanced Ventricular Assist Device with Pulse Augmentation and Automatic Regurgitant Flow Shutoff

项目摘要 连续流（CF）旋转泵已被广泛用于治疗终末期心力衰竭患者。 然而，所有现有或正在开发的CF器械都具有以下临床局限性：动脉搏动降低， 泵血栓形成或溶血的威胁，泵停止期间因回流导致晕厥和死亡的风险， 无法通过停泵测试非侵入性地评估脱机能力，狭窄的操作规范意味着 没有通用装置可用作左心室辅助装置和右心室辅助装置（分别为LVAD和RVAD）， 以及由于左心室壁抽吸进入入口而导致的潜在入口阻塞。以消除或最小化 这些缺点，我们正在开发一种创新的，先进的心室辅助设备（AVAD），来自 Cleveland Clinic的LVAD、RVAD和连续流全人工心脏（CFTAH）的特点。以下 目标是可实现的：保持生理脉动，降低泵血栓形成或溶血的风险， 通过启用自动关闭防止回流，实现泵可脱机性的非侵入性评估， 展示广泛的操作规范，使AVAD能够用作LVAD或RVAD，并避免 通过自动衰减泵输出来实现吸入事件。该提案的目标是解决 提出的概念的可行性，采取第一步走向完善，并证明了预期的 体内机械功能。具体目的是：（1）分析和提炼泵的设计特点， 模拟循环回路中的计算流体动力学研究和体外测试，以模拟不同的 血液动力学事件，（2）制造一个具有三维（3D）打印塑料外壳和叶轮的泵 适用于初步实验室研究，一个钛型泵用于急性体内实验，（3）执行 体外系统表征和溶血试验，以验证AVAD系统性能，以及（4）评价 在不同生理扰动下的三个急性体内实验中的系统性能， 证明机械功能目标和生物相容性筛选。在证明了这一点的可行性后， 在这个R21计划中，我们将申请R 01拨款，以进一步完善设备设计， 进行台架耐久性试验，并进行生物相容性试验的慢性动物研究。的 拟议的AVAD具有许多先进的功能，将改善严重心力衰竭患者的预后， 提供安全有效的心脏支持，作为移植和/或目的治疗的桥梁。

Project Summary Continuous-flow (CF) rotary pumps have been widely used to treat patients with end-stage heart failure. However, all existing or developing CF devices have the following clinical limitations: reduced arterial pulsatility, threat of pump thrombosis or hemolysis, risk of syncope and death from backflow during pump stoppage, inability to non-invasively evaluate weanability by pump-off test, narrow operating specifications meaning there is no universal device for use as both left and right ventricular assist devices (LVAD and RVAD, respectively), and potential inlet obstruction from suctioning of left ventricular wall into the inlet. To eliminate or minimize these drawbacks, we are developing an innovative, advanced ventricular assist devices (AVAD), derived from features of Cleveland Clinic's LVAD, RVAD, and continuous-flow total artificial heart (CFTAH). The following goals are attainable: maintain physiological pulsatility, reduce the risk of pump thrombosis or hemolysis, prevent backflow by enabling automatic shutoff, enable non-invasive evaluation of pump weanability, demonstrate wide operating specifications, enabling use of the AVAD as either an LVAD or RVAD, and avoid suction events by automatically attenuating pump output. The goals of this proposal are to address the feasibility of the proposed concept, take the first steps toward refinement, and demonstrate the intended mechanical function in vivo. The Specific Aims are: (1) analyze and refine the pump design features by a computational fluid dynamics study and in vitro testing in a mock circulatory loop, to simulate varying hemodynamic events, (2) fabricate one pump with three-dimensional (3D) printed plastic housing and impellers suitable for preliminary bench studies and one titanium version pump for acute in vivo experiments, (3) perform in vitro system characterization and hemolysis testing to verify AVAD system performance, and (4) evaluate system performance in three acute in vivo experiments under varying physiological perturbations to demonstrate mechanical functional goals and biocompatibility screening. After proving the feasibility of this totally new VAD design in this R21 program, we will apply for an R01 grant to further refine the device design, perform bench endurance testing, and carry out chronic animal studies for biocompatibility testing. The proposed AVAD, with many advanced features, will improve the outcomes of patients with severe heart failure, providing safe and effective cardiac support as a bridge to transplant and/or destination therapy.