Development of a percutaneously implantable, ambulatory, long-term intravascular ventricular assist system

摘要 心力衰竭(HF)进展迅速，尽管有最佳的医疗管理和心脏再同步化 心理治疗。由于手术侵袭性，左心辅助装置仅保留用于终末期心衰。长- 为病情较轻的心力衰竭患者(III级，早期IV级)提供长期机械循环支持选择， 可能减慢或逆转心衰进程，都是有限的。为了填补这一治疗缺口，NuPulseCV(北卡罗来纳州罗利) 正在开发一种经皮释放的、可长期植入的第二代反搏动系统 (IVA)治疗心力衰竭患者。NuPulseCV静脉内动脉是为更少侵入性的经皮吸收而开发的 心脏病专家在1.5小时内在心脏导管实验室的降主动脉内植入，以及 实现患者的完全移动性。在FDA批准的一项正在进行的临床研究中，第一代静脉内注射是 使用外科方法成功地植入了80多名患者，并显示出统计学意义 心脏指数(39%)、射血分数(48%)和心力指数(35%)的血流动力学改善 超过基准值。然而，用于临床研究的第一代静脉注射需要心脏 外科医生和两名助手植入该设备，需要大约4个小时的时间，并且需要一套手术套件。在……里面 这项SBIR第一阶段研究，我们将论证经皮给药的第二代静脉注射的可行性 以提供慢性反搏动支持。 这一目标将通过(1)制造第二代静脉内动脉和植入工具来实现 设计用于经皮给药，(2)使用急、慢性绵羊模型验证可行性。 SBIR第一阶段研究的结果将用于SBIR期间经皮静脉内动脉的优化 第二阶段，这将导致FDA提交一项关键研究。 本建议书中详细介绍的计划充分利用了 由贝丝以色列女执事医疗中心(BIDMC)的一组创新医生指导的NuPulseCV。 我们的长期目标是成功地将第二代静脉注射系统引入临床环境。 作为一种治疗心力衰竭患者的长期反搏疗法，不良事件和帮助最小 恢复他们的生活质量。

ABSTRACT Heart failure (HF) rapidly progresses despite optimal medical management and cardiac resynchronization therapy. Left ventricular assist devices are reserved only for end-stage HF due to surgical invasiveness. Long- term mechanical circulatory support options for less sick heart failure patients (Class III, early Class IV), which may slow down or reverse HF progression, are limited. To fulfill this therapeutic gap, NuPulseCV (Raleigh, NC) is developing a percutaneously delivered, chronic implantable, second-generation counterpulsation system (iVAS) to treat HF patients. The NuPulseCV iVAS has been developed for less invasive percutaneous implantation in the descending aorta in a cardiac catheter laboratory by a cardiologist within 1.5 hours, and enables complete patient mobility. In an ongoing FDA approved clinical study, the first-generation iVAS was successfully implanted in over 80 patients using a surgical approach and demonstrated statistically significant hemodynamic improvements in cardiac index (39%), ejection fraction (48%), and cardiac power index (35%) over baseline values. However, the first-generation iVAS used for the clinical studies requires a cardiac surgeon and two assistants to implant the device, takes ~4 hours to implant, and requires a surgical suite. In this SBIR Phase I study, we will demonstrate feasibility of a percutaneously delivered second-generation iVAS to provide chronic counterpulsation support. This objective will be accomplished by (1) fabrication of the second generation iVAS and implant tools designed for percutaneous delivery, (2) demonstrating feasibility using acute and chronic ovine models. Results from the SBIR Phase I study will be used for optimization of the percutaneous iVAS during SBIR Phase II, which will then lead to an FDA submission for a pivotal study. The program detailed in this proposal leverages the engineering expertise and development work of NuPulseCV guided by an innovative group of physicians at Beth Israel Deaconess Medical Center (BIDMC). Our long-term objective is to successfully introduce the second generation iVAS system into the clinical setting as a long-term counterpulsation therapy to treat heart failure patients with minimal adverse events and help restore their quality of life.