A Novel Approach to Cardiac Replacement with Continuous Flow Pumps

描述（由申请人提供）：心力衰竭是美国的首要死因。为人类衰竭的心脏提供有效、可靠的机械替代品将对医疗保健产生巨大影响。然而，迄今为止，开发全人工心脏（TAH）所固有的技术挑战已被证明是令人望而却步的。最近，连续流（CF）血泵已作为心室辅助装置引入临床医学。这些泵比以前的脉动泵更小、更简单、更坚固。此外，CF 泵具有根据流入和流出压力调节泵输出的固有能力。德克萨斯心脏研究所 (THI) 的研究人员正在利用这些优势，开发一种新型连续流全人工心脏 (CF-TAH)，该心脏由两个串联使用的改良 CF 泵组成：一个专用于全身循环，另一个专用于肺循环。 CF 泵的流入敏感性使其特别适合集成到 TAH 中，因为它们具有自主平衡体循环和肺流量的潜力。 THI 使用双 CF 泵进行全心脏置换的初步动物研究已证明其可行性，可实现长达 7 周的存活期和正常的生理功能。该计划的具体目标是（1）开发 CF-TAH，使晚期心力衰竭患者重新获得有意义且可接受的生活质量，以及（2）开发 CF-TAH 操作控制系统，以响应不断变化的需求。为了实现这些目标，首席研究员 O. H. Frazier (THI) 将领导一个由德克萨斯医学中心四个机构（THI、MicroMed Cardiosculptures, Inc.、休斯顿大学和莱斯大学）组成的合作小组。将使用计算机建模和体外和体内实验来修改当前的 CF 泵技术，将两个 CF 泵集成到 CF-TAH 设计中，并开发控制系统和患者泵接口。组建的团队在医疗设备开发、机械工程、材料科学、生物工程、计算建模、动物研究和心脏手术方面拥有丰富的经验。凭借其成功的研究合作历史、地理位置以及丰富而广泛的经验和专业知识，这个多机构团队非常适合承担开发有效、可靠和经济的 TAH 这一具有挑战性但重要的任务。 公共卫生相关性 心力衰竭是美国的主要原因。该项目的目标是使用两个连续流血泵开发新型全人工心脏（TAH）。这些泵比老式的脉动泵小，因此可以植入儿童和体型较小的成人体内。连续流 TAH 也更容易控制，并且具有出色的可靠性。因此，有效、可靠的替代品（例如针对衰竭人类心脏的连续流动 TAH）的可用性将对医疗保健产生巨大影响。

DESCRIPTION (provided by applicant): Heart failure is the leading cause of death in the United States. The availability of an effective, reliable mechanical replacement for the failing human heart would have an enormous impact on health care. Nevertheless, the technical challenges inherent in developing a total artificial heart (TAH) have, to date, proven prohibitive. Recently, continuous-flow (CF) blood pumps have been introduced into clinical medicine as ventricular assist devices. These pumps are smaller, simpler, and more robust than their pulsatile predecessors. In addition, CF-pumps have the intrinsic ability to adjust pump output based on inflow and outflow pressure. Researchers at the Texas Heart Institute (THI) are capitalizing on these advantages by developing a novel continuous-flow total artificial heart (CF-TAH) comprising two modified CF-pumps used in series: one dedicated to the systemic and the other to the pulmonary circulation. The inflow sensitivity of CF- pumps makes them uniquely suited for integration into a TAH as they have the potential to autonomously balance systemic and pulmonary flow. Preliminary animal studies at THI using dual CF-pumps for total heart replacement have demonstrated feasibility, with up to 7 weeks of survival and normal physiologic function. The specific aims of this program are (1) to develop a CF-TAH that allow patients with advanced heart failure to regain meaningful and acceptable quality of life, and (2) to develop a control system for operation of the CF- TAH that responds to changing demands. To achieve these aims, the PI, O. H. Frazier (THI), will lead a collaborative group of four institutions in the Texas Medical Center (THI, MicroMed Cardiovascular, Inc., University of Houston, and Rice University). Computer modeling and in vitro and in vivo experiments will be used to modify current CF-pump technology, integrate two CF-pumps into a CF-TAH design, and develop the control system and patient-pump interface. The assembled team has extensive experience in medical device development, mechanical engineering, materials science, bioengineering, computational modeling, animal research, and cardiac surgery. On the basis of their successful history of research collaboration, geographic proximity, and wealth and breadth of experience and expertise, this multi-institutional group is uniquely suited for the challenging but important task of developing an effective, reliable, and economical TAH. PUBLIC HEALTH RELEVANCE Heart failure is the leading cause of death in the United States. The goal of this project is to develop a new total artificial heart (TAH) using two continuous-flow blood pumps. These pumps are smaller than the older, pulsatile pumps and can therefore be implanted in children and smaller adults. The continuous-flow TAH would also be simpler to control and would have excellent reliability. The availability of an effective, reliable replacement such as the continuous-flow TAH for the failing human heart would thus have an enormous impact on health care.