Self-Sensing Physiologic Control of a Rotary Mag Lev LVAD

描述(申请人提供)：心力衰竭是美国头号死亡原因，在冠心病和高血压死亡率下降的情况下，公众的发病率和死亡率负担也在增加。虽然估计有4万名充血性心力衰竭患者适合心脏移植，但每年只有2200例供体心脏可供选择，这突显了机械循环支持的必要性。在开发心血管疾病新疗法的努力中，NIH NHLBI资助了脉动型和非脉动型机械循环辅助设备(MCAD)的开发。虽然目前MCADS的使用正在增加，但如果有完全可植入和具有生理控制系统的可穿戴设备可用，将有更多的患者受益。MITI的最终目标是一种可植入的旋转式左心室辅助装置(LVAD)，带有生理控制器，用于成人心力衰竭患者的目的地治疗。提出的自感知生理控制器的关键和新颖特征是它能够使用电机和磁轴承信号来调整LVAD输出，以通过使用差压和流量估计器来响应心输出量的变化，同时避免吸力。该项目的具体目标是通过计算机模拟、体外和体内测试来设计、实施和演示MiTiHeart(R)LVAD输出的生理控制。具体地说，MITI(注册商标)的S模拟循环器系统(MCS)将进行改进，以更准确地模拟左心室血流动力学，具有差压、流量和吸力避免目标功能的生理控制算法将在MiTiHeart(注册商标)LVAD控制器中实施，并在MCS中进行评估。MCS和LVAD的电气模拟计算机模拟将被更新和调整，以匹配测量数据，以便可以模拟其他控制算法和系统物理变化的评估，包括用人体心血管系统模型替换MCS模型。最后，宾夕法尼亚州立好时医疗中心将完成活体急性动物研究，以证明生理控制器在不进入吸力的情况下调整左心输出量的能力。计划的具体目标如下：(1)设计和实施对MITI(R)MCS的改进，通过结合改进的左心室(LV)射血流动和压力模拟，更准确地模拟左心室血流动力学。(2)修改第一阶段开发的MCS的数学模型，以接受包含生理控制算法的增强型LVAD性能模型。调整集成的数学模型以反映在MCS中测量的性能。使用优化的模型评估LVAD和控制器对模拟变化的响应能力，首先在MCS模型中，然后使用人类心血管系统(CVS)模型。然后将使用增强的模型对MCS和CVS模型进行仿真，以评估LVAD和生理控制系统在各种条件下的性能，以验证控制器在避免吸力的同时随着生理需求的变化而改变输出的能力。(3)通过体外试验评价更新后的MCS的生理控制系统性能、吸力避免、泵压差和流量估算。第一阶段开发的生理控制算法和体系结构将在dSPACE数字控制硬件系统中实现。然后，该控制系统将与MiTiHeart LVAD一起使用，以在更新的MCS中对建议的控制系统进行表征和验证。将在不同的模拟心脏条件下进行MCS测试，以鼓励吸力事件。(4)进行三个活体急性动物实验，以验证生理控制器的性能，包括估计差压和流量，以及检测和避免吸力，其中动物心脏CO将被药物修饰。与公共健康相关：根据美国心脏协会[1]的数据，每年约有100万美国人死于心脏病，近470万美国人患有充血性心力衰竭(CHF)，这是一种慢性疾病，至少有一个心腔的泵血不足以满足身体的需要。由于每年有50多万新的CHF病例和近40,000名心脏移植候选患者仅有2,200个供体心脏可供选择，因此迫切需要新的治疗方案，如机械循环辅助装置或心脏辅助泵[2]。早期开发的成功导致了循环辅助设备的短期使用[2，3，4]，然而，需要新的开发来使这些心脏辅助设备的长期使用成为可能。

DESCRIPTION (provided by applicant): Heart failure is the number one cause of death in the United States and presents an increasing public burden of morbidity and mortality even as the mortality from coronary artery disease and hypertension is decreasing. While an estimated 40,000 congestive heart failure patients are candidates for heart transplantation, only 2,200 donor hearts are made available each year highlighting the need for mechanical circulatory support. In its efforts to develop new treatments of cardiovascular diseases, the NIH NHLBI has funded development of pulsatile and nonpulsatile mechanical circulatory assist devices (MCADs). While, current use of MCADs is increasing, many more patients would benefit if fully implantable and wearable devices with physiologic control systems were available. MiTi's ultimate goal is an implantable rotary Left Ventricular Assist Device (LVAD) with physiologic controller for destination therapy in adult heart failure patients. Key and novel features of the proposed self sensing physiologic controller are its ability to use motor and magnetic bearing signals to adjust LVAD output in response to cardiac output changes through the use of differential pressure and flow estimators all while avoiding suction. The specific goals of this project are to design, implement and demonstrate physiologic control of the MiTiHeart(R) LVAD output through computer simulations, in vitro and in vivo tests. Specifically, MiTi(R)'s Mock Circulator System (MCS) will be modified to more accurately model left ventricle hemodynamics, the physiologic control algorithms having differential pressure, flow and suction avoidance objective functions will be implemented in the MiTiHeart(R) LVAD controller and evaluated in the MCS. Electric analog computer simulations of the MCS and LVAD will be updated and tuned to match the measured data so that evaluations of additional control algorithms and system physical changes can be simulated including replacing the MCS model with a human cardiovascular system model. Finally, in vivo acute animal studies will be completed at Penn State Hershey Medical Center to demonstrate the ability of the physiologic controller to adjust LVAD output without entering suction. The following Specific Aims are planned: (1) Design and implement modifications to the MiTi(R) MCS to more accurately model left ventricle hemodynamics by incorporating improved simulation of left ventricle (LV) ejection flow and pressure. (2) Modify the mathematical model of the MCS developed in Phase I to accept an enhanced LVAD performance model including the physiologic control algorithm. Tune the integrated mathematical model to reflect the measured performance in the MCS. Use the optimized model to assess the ability of the LVAD and controller to respond to simulated changes first in the MCS model and then with a human cardiovascular system (CVS) model. Simulations with both MCS and CVS models will then be performed using the enhanced models to assess performance of the LVAD and physiologic control system under a wide variety of conditions to verify the ability of the controller to vary output with changing physiologic demand while also avoiding suction. (3) Evaluate the physiologic control system performance, suction avoidance and pump differential pressure and flow estimations via in vitro testing in the updated MCS. The physiologic control algorithms and architecture developed under Phase I will be implemented in a dSpace digital control hardware system. The control system will then be used with the MiTiHeart LVAD to characterize and verify the proposed control system in the updated MCS. MCS testing under different simulated heart conditions that encourage suction events will be conducted. (4) Conduct three in vivo acute animal studies to validate performance of the physiologic controller including estimating differential pressure and flow as well as detecting and avoiding suction where the animal heart CO will be pharmacologically modified. PUBLIC HEALTH RELEVANCE: According to the American Heart Association [1], approximately one million Americans die each year from heart disease and almost 4.7 million Americans have congestive heart failure (CHF), a chronic condition in which at least one chamber of the heart is not pumping well enough to meet the body's need. With more than half a million new cases of CHF and only 2,200 donor hearts available for almost 40,000 heart transplantation candidates every year, there is a pressing need for new treatment options such as mechanical circulatory assist devices or heart assist pumps [2]. The success of early developments has resulted in the use of circulatory assistance for short durations [2, 3, 4], however new developments are needed to make long duration use of these heart assist devices possible.