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）的使用越来越多，以服务于越来越多的终末期充血性心力衰竭患者。然而，高达40%的患者有明显的右心室（RV）衰竭，这限制了植入式左心室辅助器治疗的应用。右心室衰竭导致两个问题：前向血流减少和右心压力升高，导致肝、肾和腹部器官被动充血。这两个因素都会导致多器官功能衰竭，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肌力支持或右心室辅助装置（RVAD）支持。临床可用的RVADs不是植入式装置，由于血液相容性差、感染率高、长期耐久性差、需要抗凝、需要住院、高死亡率和不理想的生活质量而存在一些局限性。我们报道了左心室辅助器支持的患者预后较差，他们也需要外部左心室辅助器支持或长时间的肌力支持。一个安全、有效、可植入的RVAD可以挽救许多此类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。旋转组件完全悬浮，在运行过程中无机械接触或磨损。如果CorAide左室辅助装置（LVAD）可以改良并作为RVAD使用，那么由此产生的CorAide双心室辅助装置（BVAD）将是永久支持（目的治疗）的理想系统。本项目的主要目的是设计、开发和临床评估可作为严重双心室衰竭患者植入式BVAD组成部分的植入式RVAD。具体目标是(1)设计和开发一个基于CorAide植入式RVAD使用,第三代血液离心泵,(2)设计和开发一个先进的故障安全控制算法能够固定速度或平衡RVAD和使用性能的自动模式,(3)进行体内表征测试的系统作为一个孤立的RVAD和作为BVAD CorAide使用,(4)进行体内和体外的完整RVAD系统的可靠性测试,(5)获得FDA批准的研究器械豁免（IDE），并使用机构批准的项目进行临床试点研究，以进行患者选择和数据收集。

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.