Physiological Adaptive COntrol of Continuous Flow Ventricular Assist Devices

描述（由申请人提供）：使用左心室辅助装置（lvad）已经成为终末期心力衰竭患者的一种可行的治疗选择。这些装置通常用作移植或目的地治疗的桥梁，并且由于改进的装置设计降低了不良事件的风险，LVAD支持也被认为是III级心力衰竭患者的一种选择。最近，连续流lvad因其体积小、可靠性高而变得越来越普遍。然而，与上一代脉冲装置相比，这些装置的控制可能具有挑战性。当前的控制系统以医生设定的固定速度运行泵。速度设置得足够高，以提供足够的循环支持，但又不能太快，以免引起吸痰和心室塌陷。这些控制系统不能根据生理需求增加流量，因此，使用这些装置的患者的运动能力有限。随着患者现在离开医院并恢复日常活动，有必要建立一个响应患者需求的控制系统。该研究的主要目的是开发一种连续血流血泵的控制系统，该系统可以降低吸入风险，并根据循环需求调整泵流量。我们已经开发了一种压力传感器，可以集成到连续流LVAD的入口，并保持无缝的血液界面。使用这种压力传感器，将开发以下具体目标的控制系统。(1)在进口压力信号中可以检测到心室吸力的开始为负瞬态，可以立即降低泵速来解决吸力事件。(2)峰值进口压力信号可用于反馈控制回路，以模拟Frank-Starling机制，并在心室预负荷变化的响应下维持足够的循环支持。(3)控制系统设定点可根据检测到的吸力事件频率自动调整，以适应生理变化。该控制系统已在体外使用FDA批准的HeartMate II轴流泵开发，并在最初的急性绵羊研究中进行了测试。我们建议在一系列急性和慢性绵羊研究中进一步开发和评估控制系统。宾夕法尼亚州立大学人工器官部门在LVAD开发和大型动物试验方面拥有丰富的经验和专业知识，我们将在拟议的研究中利用这些经验和专业知识。

DESCRIPTION (provided by applicant): The use of left ventricular assist devices (LVADs) has been a viable therapeutic option for end-stage heart failure patients. These devices are commonly used as bridge-to-transplant or destination therapy, and as the risk of adverse events has been reduced with improved device design, LVAD support is being considered as an option for class III heart failure patients as well. Recently, the use of continuous flow LVADs has become common due to their small size and improved reliability. However, control of these devices can be challenging as opposed to the previous generation of pulsatile devices. Current control systems operate the pump at a fixed speed set by the clinician. The speed is set high enough to provide adequate circulatory support but not too high as to cause suction and ventricular collapse. These control systems cannot increase flow in response to physiologic demand and therefore, patients with these devices have limited exercise capacity. As patients are now leaving the hospital and returning to their daily activities, a control system that respond to patient demand is necessary. The primary objective of the proposed research is to develop a control system for continuous flow blood pumps that can reduce the risk of suction and adapt pump flow in response to circulatory demand. We have developed a pressure sensor that can be integrated to the inlet of a continuous flow LVAD and maintain a seamless blood interface. Using this pressure sensor, the following specific aims of the control system will be developed. (1) The onset of ventricular suction can be detected as a negative transient in the inlet pressure signal, and pump speed can be immediately reduced to resolve the suction event. (2) The peak-to-peak inlet pressure signal can be used in a feedback control loop to mimic the Frank-Starling mechanism and maintain adequate circulatory support in response to changes in ventricular preload. (3) The control system set point can be automatically adjusted based on the frequency of detected suction events in order to adapt to physiologic changes. The control system has been developed in vitro using the FDA approved HeartMate II axial flow pump, and tested in an initial acute sheep study. We propose to further develop and evaluate the control system in a series of acute and chronic sheep studies. The Penn State Division of Artificial Organs has extensive experience and expertise in LVAD development and large animal testing that we will utilize for the proposed research.