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: 10115789
• 负责人: Kiyotaka Fukamachi
• 金额: $ 74.64万
• 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 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115789
• 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）已经是成人终末期心脏病患者的标准治疗 失败然而，在患有先天性心脏病（CHD）的儿科患者中， 目前可用。先天性异常的儿童患者可能会很难使用心室辅助 维持血流动力学的装置（VAD）。虽然心脏移植是一种理想的治疗方法， 适合小孩子的非常有限。尽管全人工心脏（TAH）是复杂心脏病的替代方案， 心脏异常，不存在儿科TAH，除了SynCardia的50 cc全人工心脏， 试验用器械豁免临床研究。该装置比常规的70 cc TAH小，但 仅适用于体表面积（BSA）≥ 1.2 m2的患者，即，相当于一个11岁的孩子的 该提案的目标是基于克利夫兰诊所的连续流TAH（CFTAH）开发儿科TAH， 设计用于成人患者（R 01 HL 096619）。与成人CFTAH相似，该儿科CFTAH（P- CFTAH）设计有一个电机和一个由流体动力轴承支撑的旋转组件;它 无阀和无传感器，并具有产生脉动流、自平衡左右循环的能力 无需电子干预，自动控制速度。成人慢性动物实验 CFTAH在3个月内表现出稳定的血流动力学和良好的生物相容性。有可能 将该CFTAH的尺寸减小至直径小30%（3.5 cm）和长度短30%（4.8 cm）， 器械总体积的1/3，因此可植入大多数BSA ≥ 0.3 m2婴儿的胸部。 1.5-4.5 L/min的泵流量范围将支持体重高达50 kg的患者（平均体重为14- 20 kg）。 岁的孩子）。对于目标治疗，当患者增长超过4.5 L/min的要求时， 通过断开P-CFTAH的流入和流出端口，可将P-CFTAH替换为成人CFTAH 从其各自的流入端袖带和流出端移植物，并在心肺下连接新的成人CFTAH 旁路。实现这一目标的具体目标是：（1）改进我们的初始P-CFTAH原型装置， 通过使用经验证的计算流体动力学分析确定的液压性能和生物相容性，以及 包括新的制造改进，也适用于成人CFTAH，（2）执行 术中拟合研究，以确认最小患者尺寸和关键尺寸，从而确定拟合 要求，（3）进行体外系统表征、溶血试验和耐久性试验，以验证 P-CFTAH满足系统性能要求，以及（4）在体内进行急性和慢性试验 验证血液动力学响应、自调节机械设计、系统性能 和生物相容性。该项目的成功完成将证明其可行性。 方法应用于P-CFTAH，并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

项目成果

Use of a Mechanical Circulatory Support Simulation to Study Pump Interactions With the Variable Hemodynamic Environment.

使用机械循环支持模拟来研究泵与可变血流动力学环境的相互作用。

• DOI: 10.1111/aor.13287
• 发表时间: 2018
• 期刊: Artificial organs
• 影响因子: 2.4
• 作者: Horvath,DavidJ;Horvath,DennisW;Karimov,JamshidH;Byram,Nicole;Kuban,BarryD;Miyamoto,Takuma;Fukamachi,Kiyotaka
• 通讯作者: Fukamachi,Kiyotaka