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

项目摘要 机械循环支持(MCS)已成为成人终末期心脏病患者的标准治疗方法 失败了。然而，在患有先天性心脏病(CHDS)的儿童患者中，没有可植入的装置 目前可用。儿科患者的先天畸形会使使用脑室辅助治疗变得困难 维持血流动力学的装置(VAD)。虽然心脏移植可能是一种理想的治疗方法，但捐赠者的心脏 适合小孩子的非常有限。尽管全人工心脏(TAH)是复杂心脏的一种替代方案 心脏异常，除SynCardia的50cc总人工心脏低于 研究设备豁免临床研究。这款设备比他们常规的70cc TAH小，但 仅适用于身体表面积为≥1.2m2的患者，即平均11岁的儿童。这个 该方案的目标是在克利夫兰诊所的连续流动式TAH(CFTAH)的基础上开发一种儿科TAH。 专为成人患者设计(R01HL096619)。与成人CFTAH相似，儿童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；它是 无阀和无传感器，能够产生搏动性流动，左右循环自我平衡 无需电子干预，自动控制速度。成人慢性动物实验 术后3个月，CFTAH血流动力学稳定，生物相容性良好。这是可能的 将此CFTAH的直径缩小30%(3.5厘米)，长度缩短30%(4.8厘米) 1/3的装置体积，这样它就可以植入大多数BSA为≥0.3m2的婴儿的胸部。 泵的流量范围为1.5-4.5 L/分钟，可支持体重达50公斤(平均体重14-30公斤)的患者 1岁的儿童)。对于目的地治疗，当患者的生长超过4.5L/分钟的要求时， 通过断开P-CFTAH的流入和流出端口，可以用成年CFTAH替换P-CFTAH 从它们各自的流入袖带和流出端移植物，在体外循环下连接一个新的成人CFTAH 旁路。实现这一目标的具体目标是：(1)改进我们最初的P-CFTAH原型装置，用于 水力性能和生物兼容性，使用经过验证的计算流体动力学分析，以及 包括新的制造改进，这些改进也应用于成人CFTAH，(2)执行 术中适合性研究以确定最小患者尺寸和确定适合性的关键尺寸 要求，(3)进行体外系统表征、溶血试验和耐力试验，以验证 P-CFTAH满足系统性能要求，(4)在体内进行急性和慢性 实验验证血流动力学响应、自动调节机械设计、系统性能、 和生物兼容性。这项计划的成功完成将证明这一计划的可行性 该方法应用于P-CFTAH，最终为临床医生和儿科患者提供了有价值的 治疗心力衰竭的选择。

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.