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.

项目概要 机械循环支持（MCS）已经成为成年心脏病终末期患者的标准治疗方法 然而，对于患有先天性心脏病 (CHD) 的儿科患者，没有植入式装置。 目前，儿科患者的先天性异常可能导致难以使用心室辅助。 虽然心脏移植可能是一种理想的治疗方法，但捐赠心脏。 尽管全人工心脏（TAH）是复杂的替代品，但适合小孩子的情况非常有限。 心脏异常，除 SynCardia 的 50cc 全人工心脏外，不存在儿科 TAH 研究设备豁免临床研究 该设备比常规 70cc TAH 小，但 仅适用于体表面积 (BSA) ≥ 1.2 m2 的患者，即平均 11 岁的患者。 该提案的目标是基于克利夫兰诊所的连续流 TAH (CFTAH) 开发一种儿科 TAH， 设计用于成人患者 (R01HL096619)，与成人 CFTAH 类似，这种儿童 CFTAH (P-)。 CFTAH) 设计有一台电机和一个由流体动压轴承支撑的旋转组件； 无阀、无传感器，能产生脉动流，左右循环自平衡 无需电子干预，自动控制成人慢性动物实验速度。 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。 将此 CFTAH 的直径减小 30%（3.5 厘米），长度减小 30%（4.8 厘米） 占装置总体积的1/3，可以植入大多数BSA≥0.3 m2的婴儿的胸部。 1.5-4.5 L/min 的泵流量范围可支持体重达 50 kg 的患者（14-4.5 L/min 的平均体重） 对于目标治疗，当患者生长超过 4.5 L/min 的要求时， 通过断开 P-CFTAH 的流入和流出端口，P-CFTAH 可以被成人 CFTAH 替代 从各自的流入袖带和流出移植物中取出，并在心肺下连接新的成人 CFTAH 实现这一目标的具体目标是： (1) 完善我们最初的 P-CFTAH 原型设备。 通过使用经过验证的计算流体动力学分析来确定水力性能和生物相容性，以及 包括新的制造改进，这些改进也应用于成人 CFTAH，(2) 执行 术中验配研究，以确认最小患者体型和关键尺寸，以确定验配 (3) 进行体外系统表征、溶血测试和耐久性测试以验证 P-CFTAH 满足系统性能要求，并且 (4) 在体内执行急性和慢性 验证血流动力学响应、自调节机械设计、系统性能的实验， 该计划的成功完成将证明该计划的可行性。 方法应用于 P-CFTAH，并最终为东北地区和儿科患者提供有价值的信息 心力衰竭的治疗选择。

项目成果

Initial in vitro testing of a paediatric continuous-flow total artificial heart.

儿科连续流动全人工心脏的初步体外测试。

• 发表时间: 2018-06-01
• 作者: Fukamachi, Kiyotaka;Karimov, Jamshid H;Horvath, David J;Sunagawa, Gengo;Byram, Nicole A;Kuban, Barry D;Moazami, Nader
• 通讯作者: Moazami, Nader

A simulation tool for mechanical circulatory support device interaction with diseased states.

机械循环支持装置与疾病状态相互作用的模拟工具。

• 发表时间: 2020-06
• 作者: Horvath, David J;Horvath, Dennis W;Karimov, Jamshid H;Kuban, Barry D;Miyamoto, Takuma;Fukamachi, Kiyotaka
• 通讯作者: Fukamachi, Kiyotaka

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。

• 发表时间: 2018-12
• 影响因子: 2.4
• 作者: Horvath, David J;Horvath, Dennis W;Karimov, Jamshid H;Byram, Nicole;Kuban, Barry D;Miyamoto, Takuma;Fukamachi, Kiyotaka
• 通讯作者: Fukamachi, Kiyotaka

Artificial Deep Neural Network for Sensorless Pump Flow and Hemodynamics Estimation During Continuous-Flow Mechanical Circulatory Support.

用于连续流动机械循环支持期间无传感器泵流量和血流动力学估计的人工深层神经网络。

• 发表时间: 2023-07-01
• 作者: Kuroda, Taiyo;Kuban, Barry D;Miyamoto, Takuma;Miyagi, Chihiro;Polakowski, Anthony R;Flick, Christine R;Karimov, Jamshid H;Fukamachi, Kiyotaka
• 通讯作者: Fukamachi, Kiyotaka