Development of an intravascular circulatory support device for high-risk for percutaneous coronary intervention and cardiogenic shock

本提案的目的是继续对一种新的 在高风险经皮冠状动脉介入术期间使用的经皮机械循环支持（pMCS）装置 介入治疗（PCI）和心源性休克（CS）。PCI和CS的高发生率是显著的， 在世界范围内不断增加，在卫生保健资源和成本方面构成了重大负担。电流 治疗选择，包括药物和其他医疗设备，受到无效，不足， 支持、不良事件和/或需要大手术干预。为了满足这一需求，RT心脏 系统公司（RTCS，卡里NC）开发了一种新型血泵技术，可实现更好的血流动力学 比以前的支持。其他公司报告亚治疗主动脉瓣的高“峰值流量” 指示患者预后不良和/或严重主动脉瓣关闭不全的压力。RTCS设备提供 平均流量超过4 L/min，平均主动脉压为80 mmHg，足以恢复终末器官 灌注。其它已知的装置在这种治疗条件下只能产生3L/min或更小的平均流量。 通过广泛的血泵设计，开发了HeartWare HVAD、MVAD和脑室内 MVAD家族的慢性LVAD，RTCS已经实现了这种高水平的支持与低水平的血液创伤。 随后，RTCS拥有专业知识，经验和信心，我们将实现我们的目标， 将有竞争力的pMCS器械商业化，以改善高风险PCI和CS患者人群的治疗。 专有的RT心脏系统pMCS设备（美国专利申请15/676，281）由 微型轴流式泵（2叶片叶轮，3叶片扩散器）和血管内马达（开槽， 无刷直流电机）通过短柔性驱动系统连接。设备灵活性提高了植入 以及当装置适应于天然左心室解剖结构时对闭塞的抵抗力。短驱动系统 设计，包括轴承材料的选择，不需要润滑系统的外部清洗， 所有其他已知设备都需要。pMCS装置的高液压效率减少了血液创伤， 所需的电机扭矩和转速，以达到设计流量。电机效率高， 所需功率和散热负载。先前的研究与概念验证测试的严谨性是 通过完成流动可视化（容量、清洗、血液保存）和 体外（液压和机电性能）分析。 在第一阶段，我们将（1）完成pMCS电机系统的制造（目标1）;（2）演示 静态（HQ曲线）和动态（血液动力学）模拟回路模型的工程性能（目标1），（3） 在30天系统可靠性测试中证明系统可靠性（目标1），（4）证明生理有效性 （血流动力学，血液，成像）在大型动物模型（目的2），和（5）评估手术放置在一个 大型动物模型（目标2）。RTCS pMCS系统可行性的成功演示将包括：（1） 新颖的驱动系统可靠性，（2）达到工程性能基准，（3）生理功效（泵 流动，最小溶血），和（4）装置体内输送和定位。共同地，一旦成功 证明满足设计基准和研究指标（第一阶段），我们将努力实现设计 冷冻，完成符合良好生产规范（GMP）的验证和确认测试， 和临床前试验符合良好实验室规范（GLP）以及我们所有的工程控制 用于支持PCI临床试验IDE申请的文件、临床前试验数据和分析 CS患者。我们的愿景是成功地将pMCS系统和一系列基于导管的 产品用于成人高风险PCI和CS以及右心和双心室衰竭的临床实践 成人和儿童患者的治疗。

The objective of this proposal is to continue engineering development and pre-clinical testing of a novel percutaneous mechanical circulatory support (pMCS) device for use during high risk percutaneous coronary intervention (PCI) and cardiogenic shock (CS). The high-incidence of PCI and CS are significant and increasing worldwide, representing a major burden in terms of health care resources and costs. Current treatment options, including medications and other medical devices, are limited by ineffectiveness, insufficient support, adverse events, and/or require major surgical intervention. To address this need, RT Cardiac Systems (RTCS, Cary NC) has developed novel blood pump technology enabling greater hemodynamic support than previously possible. Other companies report high “peak flows” at sub-therapeutic aortic pressures indicative of poor patient prognosis and/or severe aortic insufficiency. The RTCS device provides mean flow over 4 L/min against mean aortic pressure of 80 mmHg, which is sufficient to restore end organ perfusion. Other known devices can only produce mean flows of 3 L/min or less at this therapeutic condition. With extensive blood pump design gained developing the HeartWare HVAD, MVAD, and intraventricular MVAD family of chronic LVAD’s, RTCS has achieved this high level of support with low levels of blood trauma. Subsequently, RTCS has the expertise, experience, and confidence that we will achieve our objective of commercializing a competitive pMCS device to improve therapy for high-risk PCI and CS patient populations. The proprietary RT Cardiac System pMCS device (US patent application 15/676,281) consists of a miniaturized axial flow pump (2-bladed impeller, 3-bladed diffuser) and an intravascular motor (slotted, brushless DC motor) connected via a short flexible drive system. The device flexibility improves implantation and resistance to occlusion as the device adapts to the native left ventricle anatomy. The short drive system design, including bearing material selections, does not require an external purge of lubrication system that is required of all other known devices. The high hydraulic efficiency of the pMCS device reduces blood trauma, required motor torque, and rotational speed to achieve design flow rates. The high motor efficiency reduces the power required and heat dissipation load. Rigor of prior research with proof-of-concept testing was demonstrated as evidenced by completion of flow visualization (capacity, washing, blood preservation) and in vitro (hydraulic and electro-mechanical performance) analyses. In this phase I project, we will (1) complete fabrication of the pMCS motor system (Aim 1); (2) demonstrate engineering performance in static (HQ curves) and dynamic (hemodynamics) mock loop model (Aim 1), (3) demonstrate system reliability in 30-day system reliability testing (Aim 1), (4) demonstrate physiologic efficacy (hemodynamics, blood, imaging) in a large animal model (Aim 2), and (5) evaluate surgical placement in a large animal model (Aim 2). Successful demonstration of feasibility of the RTCS pMCS system will include: (1) novel drive system reliability, (2) achieve engineering performance benchmarks, (3) physiologic efficacy (pump flow, minimal hemolysis), and (4) device in vivo delivery and positioning. Collectively, upon successful demonstration of meeting design benchmarks and study metrics (phase I), we will work to achieve a design freeze, complete verification and validation testing in compliance with Good Manufacturing Practices (GMP), and pre-clinical testing in compliance with Good Laboratory Practices (GLP) with all of our engineering control documents and pre-clinical test data and analyses used to support a IDE application for a clinical trial in PCI and CS patients. Our vision is to successfully translate the pMCS system and a family of catheter-based products into clinical practice for high-risk PCI and CS in adults as well right heart and biventricular failure therapies in adult and pediatric patients.