Optimization of Right and Left Ventricular Coupling During Mechanical Circulatory Support

机械循环支持过程中左右心室耦合的优化

• 批准号: 10748767
• 负责人: Kimberly K Lamberti
• 金额: $ 4.77万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10748767
• 关键词: Blood; Blood Vessels; Cardiac; Cardiogenic Shock; Cardiopulmonary Bypass; Cardiovascular system; Career Choice; Circulation; Clinical; Collaborations; Combined Modality Therapy; Congestive Heart Failure; Coupled; Coupling; Data; Development; Devices; Disease; Engineering; Environment; Extracorporeal Membrane Oxygenation; Growth; Health; Heart; Heart Diseases; Incidence; Individual; Industry; Institution; Knowledge; Laboratories; Left; Left ventricular structure; Lung; Mechanics; Methods; Nature; Organ; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Perfusion; Physics; Physiological; Physiology; Play; Pulmonary Circulation; Ramp; Recording of previous events; Reporting; Research; Research Contracts; Research Personnel; Resources; Rest; Right ventricular structure; Role; Science; Scientist; Series; Shock; Side; Stimulus; Stress; Stress Tests; Structure; System; Technology; Testing; Therapeutic; Time; Titrations; Training; Training Programs; Translational Research; Venous; Ventricular; Ventricular Function; Withdrawal; Work; experience; heart circulation; heart function; hemodynamics; improved; improved outcome; innovation; insight; interest; left ventricular assist device; mechanical circulatory support; mortality; novel; patient tolerability; porcine model; professor; research facility; response; right ventricular failure; skills; stress reduction; teacher; vascular bed; ventricular assist device

PROJECT SUMMARY Cardiogenic shock, a devastating outcome of decompensated heart disease, has both increased in incidence and maintained remarkably high mortality rates near 50%. Mechanical circulatory support is emerging with the unique ability to decouple cardiac supply and demand to sustain end-organ perfusion while reducing cardiac work. However, methods to guide device selection and titration are limited. One aspect of this which remains understudied is the importance of interactions between the left and right ventricles and their power over patient tolerance to device support. This is particularly critical as >40% of patients with left-sided support have been reported to experience right heart failure after device initiation, making this a major limitation to clinical utility. Thereby, this research employs a mechanistic approach to define the nature of right-left ventricular coupling in health and cardiogenic shock and its governance of mechanical circulatory support outcomes. We will employ a novel porcine model of graded left and right ventricular collapse to determine metrics critical to right and left heart adaptability individually, and those which contextualize the two to assess ventricular coupling. We will use this understanding to assess the biventricular response to two forms of clinical mechanical support. First, we will test a percutaneous left ventricular assist device, which employs a mechanism of continuously unloading the left ventricle to increase forward flow from the heart. The second technology will be veno-arterial extracorporeal membrane oxygenation support, which increases perfusion through venous withdrawal and retrograde return into the systemic circulation; this mechanism is particularly notable for unloading and reducing stress on the right heart and pulmonary circulation. Controlled stimulus provided by each technology will allow for assessment of the dynamic response according to ventricular coupling state. This project implements mechanistic analysis of the ability of each ventricle to respond to stress, as well as dynamic assessment (rather than classic static metrics) of ventricular-ventricular interactions (including serial interactions through the pulmonary circulation, parallel interactions through shared intracardiac structures, and synchronous interactions in time). In doing so, this work will provide insight into the governing factors over the response to mechanical support, allowing for improvements in device selection and titration, and ultimately improve outcomes from the devasting consequences of cardiogenic shock. I am excited to conduct this work with MIT Professor Elazer Edelman and to couple the research with a rigorous training plan which will allow me to grow as a scientist, communicator, and teacher. I am blessed to be at an institution and laboratory which provides all resources to complete this novel work and creates a research environment and training program that supports me in advancing towards independent translational research.

项目总结 心源性休克是失代偿心脏病的一种毁灭性后果，其发病率既增加了 并将死亡率维持在接近50%的水平。机械循环支持正在随着 独特的能力，使心脏供需分离，以维持终末器官灌流，同时减少心脏 工作。然而，指导设备选择和滴定的方法是有限的。这其中的一个方面仍然存在 未被充分研究的是左、右心室相互作用的重要性及其对患者的影响。 对设备支持的容忍度。这一点尤其重要，因为40%接受左侧支持的患者 据报道，在设备启动后发生右心衰竭，使这一点成为临床应用的主要限制。 因此，本研究采用一种机械方法来定义右室-左室偶联的性质。 健康与心源性休克及其对机械循环支持结果的控制。 我们将使用一种新的猪左室和右室衰竭模型来确定关键指标 分别对右心和左心的适应性，以及那些将两者联系起来评估心脏的 耦合。我们将利用这一理解来评估两种临床机械形式的双室反应。 支持。首先，我们将测试一种经皮左心室辅助装置，它采用了 持续地卸载左心室，以增加来自心脏的前向血流。第二项技术将是 静脉-动脉体外膜氧合支持，通过静脉增加灌注量 退出和逆行返回到体循环；这一机制对 减轻右心和肺循环的压力。由各自提供的受控刺激 这项技术将允许根据心室耦合状态评估动态反应。 该项目实现了对每个脑室对压力的反应能力的机械分析，以及 室-室相互作用的动态评估(而不是经典的静态指标)(包括序列 通过肺循环的相互作用，通过共享的心内结构的平行相互作用，以及 时间上的同步交互)。在这样做的过程中，这项工作将提供对 对机械支持的响应，允许改进设备选择和滴定，最终 改善心源性休克的破坏性后果。 我很高兴能与麻省理工学院的埃拉泽·埃德尔曼教授一起进行这项工作，并将这项研究与一个 严格的培训计划，让我成长为一名科学家、沟通者和教师。我很幸运能成为 在一个机构和实验室，该机构和实验室提供所有资源来完成这项新工作，并创造了一项研究 支持我走向独立翻译研究的环境和培训计划。