Computational and In Vivo Analysis of Applied Apical Torsion for Cardiac Support

描述（由申请人提供）：本项目的目标是确定施加的心尖扭转是否可用作辅助衰竭心脏的一种手段，而不接触血液。这种治疗心力衰竭的新方法旨在增强心室的正常扭转运动，这是患病心脏中经常缺失的重要收缩成分。如果这种方法被证明是有效的，它可以用于短期和长期心脏支持，而不会产生与血液接触器械相关的血液学风险。这项技术有可能通过提供一种简单而廉价的机械循环支持手段来改善患者的预后并降低整体医疗保健成本。这种方法有几个优点。首先，基于扭转的心室辅助装置（tVAD）可以快速应用，而不需要侵入性插管或危险和昂贵的抗凝药物治疗。另一个优点是，tVAD操作可以停止短暂（或甚至延长）的时间段，并再次启动，而没有血栓栓塞并发症的风险，血栓栓塞并发症妨碍了传统血泵中的这种开/关循环，如果停止超过几分钟，则必须移除或更换传统血泵。同样重要的是，急性tVAD支持所需的最昂贵的组件将是可重复使用的，从而允许硬件成本分摊到大量患者身上。初步研究表明，超生理扭转-90度或更大-可以在收缩期施加到心脏上，而不会引起心律失常、整颗心脏旋转或组织损伤。尽管令人鼓舞，但这些早期结果是有限的，因为它们是使用应用于具有正常心室几何形状的小心脏的非优化扭转装置在短时间内获得的。因此，有强烈的动机来扩展这些研究，以确定tVAD技术可在多大程度上用作改善心力衰竭患者心脏功能的有效手段。本项目的主要目标是评估这种方法的可行性，并确定在何种条件下，机械心尖扭转可以最好地用于帮助衰竭的心脏。为了实现这些目标，我们提出了以下两个具体目标：1）开发和实现一个先进的双心室计算机模型，以模拟心源性休克和慢性心力衰竭情况下各种扭转参数对心室功能的影响;和2）在体内测试原型装置以测量施加的顶端扭转对瓣膜能力的影响，确定器械是否会导致心肌组织损伤，并量化重度心力衰竭情况下的治疗获益。我们的期望是，在建议的支持期结束时，我们将确定哪种形式的心力衰竭最适合tVAD治疗，以及哪种心尖扭转模式-心脏覆盖百分比、扭转角度、扭转速度等。产生最好的结果。我们还希望在心力衰竭动物模型中使用原型tVAD实验证明这种方法的有效性。

DESCRIPTION (provided by applicant): The goal of this project is to determine whether applied apical torsion can be used as a means to assist the failing heart without contacting the blood. This novel approach to heart failure treatment is aimed at augmenting the normal twisting motion of the ventricles, which is an important contractile component often missing in diseased hearts. If this method proves effective, it could be used for both short-term and chronic cardiac support without the hematologic risks associated with blood-contacting devices. This technology has the potential to improve patient outcomes and lower overall health care costs by providing a simple and inexpensive means of mechanical circulatory support. The advantages of this approach are several. First, a torsion-based ventricular assist device (tVAD) could be applied quickly without the need for invasive cannulae or dangerous and expensive anticoagulation drug therapy. Another advantage is that tVAD operation could be stopped for brief (or even extended) periods of time and started up again without risking thromboembolic complications that preclude such on/off cycling in conventional blood pumps, which must be removed or replaced if stopped for more than a few minutes. Also of significance is the fact that the most costly components needed for acute tVAD support would be reusable, thus allowing hardware costs to be spread out over a large number of patients. Preliminary studies show that supraphysiologic torsion-90 degrees or more- can be applied to the heart during systole without causing arrhythmias, whole-heart rotation, or tissue damage. Though encouraging, these early results are limited in that as they were obtained for short periods of time using a non-optimized torsion apparatus applied to small hearts with normal ventricular geometry. There is strong incentive, therefore, to expand upon these studies in order to establish the extent to which tVAD technology can be used as an effective means to improve cardiac function in heart failure patients. The principal objectives of this project are to assess the feasibility of this approach ad determine the conditions under which mechanical apical torsion can best be used to assist the failing heart. To achieve these objectives, we propose to pursue the following two specific aims: 1) Develop and implement an advanced bi- ventricular computer model to simulate the effects of various torsion parameters on ventricular function in the setting of cardiogenic shock and chronic heart failure; and 2) Test prototype devices in vivo to measure the effects of applied apical torsion on valve competency, determine whether the device causes myocardial tissue damage, and quantify the therapeutic benefit in the setting of severe heart failure. Our expectations are that, at the conclusion of the proposed period of support, we will have determined which form(s) of heart failure are most amenable to tVAD therapy and what mode(s) of apical torsion-percent cardiac coverage, twist angle, torsion speed, etc.-produce the best results. We further expect to have demonstrated the effectiveness of this approach experimentally using a prototype tVAD in an animal model of heart failure.