Development and Clinical Testing of CorAide RVAD/BVAD

描述(申请人提供)：植入式左心室辅助装置(LVAD)的使用一直在增加，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%的患者有严重的右室(RV)衰竭，这限制了植入性LVAD治疗的有效性。RV衰竭导致两个问题：前向血流减少和右心压升高，导致肝、肾和腹部器官被动充血。这两个因素都导致了多器官衰竭，这是LVAD植入后死亡的主要原因。这类患者通常需要长时间的肌力支持或右室辅助装置(RVAD)的支持。临床上可用的RVAD不是植入性装置，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、高死亡率和不理想的生活质量，有几个局限性。我们已经报道了LVAD支持的患者预后很差，他们也需要外部RVAD支持或长期的肌力支持。一种安全、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。旋转组件完全悬挂，在操作过程中没有机械接触或磨损。如果CorAide LVAD可以被修改并用作RVAD，那么由此产生的CorAide双心室辅助装置(BVAD)将成为永久支持(目标治疗)的理想系统。该计划的主要目标是设计、开发和临床评估一种植入性RVAD，该RVAD可作为严重双室衰竭患者植入性BVAD的组成部分。具体目标是(1)设计和开发基于CorAide LVAD的植入式RVAD，即第三代离心式血泵；(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先进故障安全控制算法；(3)进行作为隔离RVAD和作为BVAD与CorAide LVAD的系统的体内表征测试；(4)对整个RVAD系统进行体内和体外可靠性测试；以及(5)获得FDA批准的研究设备豁免(IDE)，并使用机构批准的患者选择和数据收集计划进行临床试点研究。 在这个方案中，我们将在第一年设计和开发RVAD，在第二年进行表征研究，在第二和第三年进行体内和体外可靠性研究，并在第四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，使其能够获得卓越的生活质量。

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.