Development of a Miniaturized, Pediatric Continuous-Flow Total Artificial Heart with a Single Moving Part

开发具有单个移动部件的小型化儿科连续流动全人工心脏

• 批准号: 9901602
• 负责人: Kiyotaka Fukamachi
• 金额: $ 74.71万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901602
• 关键词: 1 year old; 11 year old; 14 year old; Acute; Adult; Animal Experiments; Blood Circulation; Body Surface Area; Caliber; Cardiac; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cartoons; Chest; Child; Childhood; Chronic; Clinic; Clinical Research; Complex; Destinations; Development; Devices; Dimensions; Equilibrium; Goals; Golf; Heart; Heart Transplantation; Heart failure; Hemolysis; Implant; In Vitro; Infant; Intervention; Investigation; Left; Left ventricular structure; Length; Liquid substance; Lung; Mechanics; Modeling; Motor; Operative Surgical Procedures; Outcome; Patients; Performance; Pulsatile Flow; Pump; Right ventricular structure; Speed; System; Testing; Universities; Weighing patient; Weight; base; biomaterial compatibility; boys; congenital anomaly; congenital heart disorder; design; experimental study; hemodynamics; implantable device; implantation; improved; in vivo; infection risk; left ventricular assist device; miniaturize; pediatric patients; programs; prototype; response; total artificial heart; ventricular assist device; young adult

Project Summary Mechanical circulatory support (MCS) is already a standard therapy in adult patients with end-stage heart failure. In pediatric patients with congenital heart diseases (CHDs), however, no implantable devices are currently available. Congenital anomalies in pediatric patients can make it difficult to use ventricular assist devices (VADs) to sustain hemodynamics. While heart transplantation can be an ideal therapy, donor hearts suitable for small children are very limited. Although total artificial heart (TAH) is an alternative for complex cardiac anomalies, no pediatric TAHs exist, other than SynCardia's 50cc Total Artificial Heart that is under investigational device exemption clinical study. This device is smaller than their regular 70cc TAH but is intended only for patients with a body surface area (BSA) of ≥ 1.2 m2, i.e., that of an average 11-year-old. The goal of this proposal is to develop a pediatric TAH based on Cleveland Clinic’s continuous-flow TAH (CFTAH), designed for use in adult patients (R01HL096619). Similar to the adult CFTAH, this pediatric CFTAH (P- CFTAH) is designed with one motor and one rotating assembly supported by a hydrodynamic bearing; it is valveless and sensorless and has the ability to produce pulsatile flow, self-balance left and right circulation without electronic intervention, and control speed automatically. Chronic animal experiments of the adult CFTAH have demonstrated stable hemodynamics and good biocompatibility for 3 months. It was possible to reduce the size of this CFTAH to 30% smaller in diameter (3.5 cm) and 30% shorter in the length (4.8 cm) with 1/3 of the total device volume, such that it can be implanted in the chest of most infants whose BSA is ≥ 0.3 m2. The pump flow range of 1.5-4.5 L/min will support patients weighing up to 50 kg (the average weight of 14- year-old children). For destination therapy, when the patient grows beyond the requirement of 4.5 L/min, the P-CFTAH can be replaced by the adult CFTAH, by disconnecting the inflow and outflow ports of the P-CFTAH from their respective inflow cuffs and outflow grafts and connecting a new adult CFTAH under cardiopulmonary bypass. The Specific Aims to achieve this goal are: (1) Refine our initial P-CFTAH prototype device for hydraulic performance and biocompatibility by using validated computational fluid dynamics analysis, and include new manufacturing improvements, which are also being applied to the adult CFTAH, (2) Perform intraoperative fitting studies to confirm the smallest patient size and critical dimensions to determine fitting requirements, (3) Perform in vitro system characterization, hemolysis testing, and endurance testing to verify that the P-CFTAH meets requirements for system performance, and (4) Perform acute and chronic in vivo experiments to validate hemodynamic response, the self-regulating mechanical design, system performance, and biocompatibility. The successful completion of this program will demonstrate the feasibility of this approach applied to a P-CFTAH and ultimately provide clinicians and pediatric patients with a valuable treatment option for heart failure.

项目摘要 机械循环支持（MCS）已经是终心心脏患者的标准疗法 失败。然而，在先天性心脏病（CHD）的小儿患者中，没有可植入的装置是 目前可用。小儿患者的先天异常可能会使使用心室辅助很难 维持血液动力学的装置（VADS）。心脏移植可以是理想的疗法，但供体心脏 适合小孩非常有限。尽管总人造心脏（TAH）是复杂的替代方法 心脏异常，没有小儿TAH，除了Syncardia的50cc总人工心脏以外 研究装置豁免临床研究。该设备比普通的70cc tah小，但是 仅针对身体表面积（BSA）≥1.2m2的患者，即平均11岁的患者。这 该提议的目标是根据克利夫兰诊所的连续流（CFTAH）开发儿科TAH， 设计用于成人患者（R01HL096619）。与成人CFTAH相似，该儿科CFTAH（p- CFTAH）设计的是一个电动机和一个由流体动力轴承支撑的旋转组件；这是 Valveless and Sensorless，并且具有产生脉动流动，左右流通自我平衡的能力 没有电子干预，并自动控制速度。成人的慢性动物实验 CFTAH在3个月内表现出稳定的血液动力学和良好的生物相容性。有可能 将此CFTAH的尺寸降低到直径较小的30％（3.5厘米），长度较短（4.8 cm），使用 总设备体积的1/3，因此可以将其植入大多数BSA≥0.3m2的婴儿的胸部。 1.5-4.5 L/min的泵流量范围将支持高达50 kg的患者（平均体重为14-- 一岁的孩子）。对于目的地治疗，当患者的生长超出4.5 l/min的需求时， p-cftah可以通过断开p-cftah的流入和出口端口来代替成人cftah 从各自的流入袖口和出口移植物中，并在心肺下连接新的成人CFTAH 旁路。实现此目标的具体目的是：（1）完善我们的初始P-CFTAH原型设备 通过使用经过验证的计算流体动力学分析和 包括新的制造改进，也将其应用于成人CFTAH，（2）执行 术中拟合研究以确认最小的患者大小和临界维度以确定配件 要求，（3）执行体外系统表征，溶血测试和耐力测试以验证 P-CFTAH符合系统性能的要求，（4）在体内执行急性和慢性 实验以验证血液动力学反应，自我调节的机械设计，系统性能， 和生物相容性。该计划的成功完成将证明这一点的可行性 适用于P-CFTAH的方法，最终为临床医生和儿科患者提供有价值的 心力衰竭的治疗选择。