Development and Clinical Testing of CorAide RVAD/BVAD

描述（由申请人提供）：植入式左心室辅助装置（LVAD）的使用不断增加，以服务于不断增长的终末期充血性心力衰竭患者人群。然而，高达40%的患者存在严重的右心室（RV）衰竭，这限制了植入式LVAD治疗的实用性。右心室衰竭会导致两个问题：前向血流减少和高右心压，导致肝脏、肾脏和腹部器官的被动充血。这两个因素都导致多器官衰竭，这是LVAD植入后死亡的主要原因。此类患者通常需要长时间的正性肌力支持或使用右心室辅助装置（RVAD）的支持。临床上可用的RVAD不是植入式器械，并且由于血液相容性差、感染率高、长期耐用性差、需要抗凝、需要住院、死亡率高以及生活质量不理想而具有若干局限性。我们已经报道了LVAD支持的患者预后不良，这些患者也需要外部RVAD支持或长期的正性肌力支持。安全、有效、可植入的RVAD可以挽救许多RV衰竭患者的生命。我们开发了CorAide TM LVD-4000辅助系统，该系统基于植入式第三代离心泵。旋转组件在操作期间被完全悬挂而没有机械接触或磨损。如果CorAide LVAD可以修改并用作RVAD，则由此产生的CorAide双心室辅助装置（BVAD）将是永久支持（目标治疗）的理想系统。本拟定项目的主要目的是设计、开发和临床评价可用作重度双心室衰竭患者植入式BVAD组件的植入式RVAD。具体目标是（1）设计和开发基于CorAide LVAD（第三代离心血泵）的植入式RVAD，（2）设计和开发能够平衡RVAD和LVAD性能的固定速度或自动模式的高级故障安全控制算法，（3）对系统进行体内表征测试，包括作为独立RVAD和作为带有CorAide LVAD的BVAD，（4）对完整的RVAD系统进行体内和体外可靠性测试，以及（5）获得FDA对研究器械豁免（IDE）的批准，并使用机构批准的患者选择和数据收集程序进行临床试验研究。 在本提案中，我们将在第一年设计和开发RVAD，在第二年进行表征研究，在第二年和第三年进行体内和体外可靠性研究，并在第四年和第五年进行临床试验。该计划的成功完成将为临床医生和患者提供安全有效的门诊机械支持选择，从而提高生活质量。

DESCRIPTION (provided by applicant): The use of implantable left ventricular assist devices (LVADs) has been increasing to serve the growing population of patients with end-stage congestive heart failure. However, up to 40% of patients have significant right ventricular (RV) failure that limits the utility of implantable LVAD therapy. RV failure leads to two problems: decreased forward flow and high right heart pressures that result in passive congestion of the liver, kidneys, and abdominal organs. Both factors contribute to multiorgan failure, the leading cause of death after LVAD implant. Such patients commonly require prolonged inotropic support or support with a right ventricular assist device (RVAD). Clinically available RVADs are not implantable devices and have several limitations due to poor blood compatibility, high infection rates, poor long-term durability, need for anticoagulation, need for a hospital stay, high mortality, and a less than ideal quality of life. We have reported a poor prognosis in patients with LVAD support who also required external RVAD support or prolonged inotropic support. A safe, effective, implantable RVAD could save the lives of many such patients with RV failure. We have developed the CorAide TM LVD-4000 Assist System, which is based on an implantable, third generation, centrifugal pump. A rotating assembly is fully suspended without mechanical contact or wear during operation. If the CorAide LVAD can be modified and used as an RVAD, the resulting CorAide biventricular ventricular assist device (BVAD) will be an ideal system for permanent support (destination therapy). The main objectives of this proposed program are to design, develop, and clinically evaluate an implantable RVAD that can be used as a component of an implantable BVAD for patients with severe biventricular failure. The specific aims are (1) Design and develop an implantable RVAD based on the CorAide LVAD, third generation centrifugal blood pump, (2) Design and develop an advanced fail-safe control algorithm capable of fixed speed or automatic mode that balances RVAD and LVAD performance, (3) Undertake in vivo characterization testing of the system both as an isolated RVAD and as a BVAD with the CorAide LVAD, (4) Undertake in vivo and in vitro reliability testing of the complete RVAD system, and (5) Obtain FDA approval for Investigational Device Exemption (IDE) and undertake clinical pilot studies using an institutionally approved program for patient selection and data collection. In this proposal, we will design and develop an RVAD in the first year, perform the characterization study in the second year, perform in vivo and in vitro reliability studies in the second and third years, and perform a clinical trial in the fourth and fifth years. The successful completion of this program will provide clinicians and patients with a safe and effective option for outpatient mechanical support that allows an excellent quality of life.