Physiological Adaptive COntrol of Continuous Flow Ventricular Assist Devices

描述(由申请人提供)：对于终末期心力衰竭患者，使用左心室辅助装置(LVADs)已经是一种可行的治疗选择。这些设备通常被用作移植的桥梁或目的地治疗，随着设备设计的改进，不良事件的风险已经降低，LVAD支持也被考虑作为III级心力衰竭患者的一种选择。最近，连续流LVAD的使用已经变得很普遍，因为它们体积小，可靠性提高。然而，与上一代脉动设备相比，这些设备的控制可能具有挑战性。目前的控制系统以临床医生设定的固定速度操作泵。速度被设置得足够高，以提供足够的循环支持，但又不会太高，以至于导致吸入和脑室衰竭。这些控制系统不能根据生理需求增加流量，因此，使用这些设备的患者运动能力有限。随着病人现在离开医院，回到他们的日常活动中，一个响应病人需求的控制系统是必要的。拟议研究的主要目标是开发一种连续流量血泵的控制系统，该系统可以降低吸入风险，并根据循环需求调整泵的流量。我们已经开发出一种压力传感器，可以集成到连续流左心室AD的入口处，并保持无缝的血液接口。使用该压力传感器，将开发控制系统的以下具体目标。(1)在进气压力信号中，可以检测到脑室吸气的开始是负瞬变，并且可以立即降低泵速以解决吸气事件。(2)峰峰值压力信号可用于反馈控制回路，以模拟Frank-Starling机制，并维持足够的循环支持以响应心室前负荷的变化。(3)控制系统设定值可以根据检测到的吸力事件的频率自动调整，以适应生理变化。该控制系统已经使用FDA批准的HeartMate II轴流泵在体外开发，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分部在LVAD开发和大型动物试验方面拥有丰富的经验和专业知识，我们将利用这些经验和专业知识进行拟议的研究。

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.