Infarct-related Ventricular Tachycardia Mechanisms: From Micro to Clinical

梗死相关室性心动过速机制：从微观到临床

• 批准号: 9920769
• 负责人: NATALIA A. TRAYANOVA
• 金额: $ 79.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920769
• 关键词: 3-Dimensional; Ablation; American; Anatomy; Animals; Cardiac; Catheters; Cells; Characteristics; Clinical; Clinical Data; Clinical Research; Complex; Data; Development; Diffusion; Electrophysiology (science); Environment; Family suidae; Gadolinium; Health Care Costs; Heart; Human; Image; Infarction; Interruption; Lesion; Life; Location; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medical Economics; Methodology; Modeling; Myocardial Infarction; Pathway interactions; Patients; Physiologic pulse; Procedures; Property; Resolution; Risk; Signal Transduction; Spatial Distribution; Structure; Surface; Testing; Tissues; Translating; Treatment Efficacy; Validation; Ventricular; Ventricular Tachycardia; analytical tool; base; clinical imaging; clinically significant; contrast enhanced; economic impact; experimental study; healing; heart rhythm; imaging capabilities; improved; in vivo; insight; invention; novel; simulation; stem; success; sudden cardiac death; treatment optimization

PROJECT SUMMARY Ventricular tachycardia (VT), a life-threatening fast heart rhythm, occurs frequently in patients with myocardial infarction, leading to sudden cardiac death. Catheter-based ablation offers the possibility of permanent cure by interrupting the VT reentrant circuit. Unfortunately, eliminating infarct-related VT with ablation has achieved only modest success, 50-88%. This stems from limitations associated with the current VT electrical mapping and the use of the clinical VT maps to identify the target locations for ablation. Employing new strategies that provide comprehensive understanding of the complex phenomena in the zone of infarct, and how they correlate to clinical measures is a quest of paramount clinical significance, as will lead to a significant improvement in the identification of optimal ablation targets for infarct-related VT. The overall objective of this project is to apply novel imaging and modeling methodologies to provide a comprehensive understanding of the complex micro-structural and electrophysiological (EP) factors that establish specific VT pathways in the zone of the healed infarct and to determine how these factors are reflected in clinical imaging and EP measurements. Our ability to achieve this objective stems from new developments by our team, such as the invention of a new MRI pulse sequence that allows us to acquire non- destructively images of entire human and large animal hearts ex-vivo at previously unattainable (sub-millimeter) resolution. We will use our new sub-millimeter imaging capability to acquire contrast-enhanced and diffusion- tensor MRI of swine and human hearts ex-vivo and develop individualized models from these images. These high resolution ex-vivo models will be used to test a number of novel mechanistic hypotheses elucidating how the complex spatially-distributed structural and EP characteristics of the healed infarct establish preferential VT pathways through it. We will then conduct simulation and experimental research to establish the relationship between the infarct structural and EP characteristics at the sub-millimeter scale that give rise to specific VT pathways, and the image features and electrical signatures in corresponding clinical-resolution measurements. Successful execution of the proposed studies will provide a new understanding of the signatures of the com- plex infarct-related micro-structural and EP remodeling as they are manifested in clinical measurements. The new insight will enable improved determination of the optimal ablation option for a given VT, leading to a significant advancement in the efficacy of the therapy.

项目摘要 心脏心动过速（VT）是一种威胁生命的快速心律，经常发生在心肌患者中 梗塞，导致心脏突然死亡。基于导管的消融提供了永久治愈的可能性 通过中断VT返回电路。不幸的是，消除与梗塞相关的VT已经实现了 只有微不足道的成功，50-88％。这源于与当前VT电气映射相关的局限性 以及使用临床VT图来识别烧蚀目标位置。采用新策略 提供对梗塞区域中复杂现象的全面理解，以及它们如何相关 临床措施是对最重要的临床意义的追求，这将导致显着改善 梗塞相关VT的最佳消融靶标识别。 该项目的总体目的是应用新颖的成像和建模方法来提供 对复杂的微观结构和电生理（EP）因子的全面理解 在治愈的内部区域中建立了特定的VT途径，并确定这些因素如何 在临床成像和EP测量中反映了。我们实现这一目标的能力源于新的 我们团队的发展，例如新的MRI脉冲序列的事件，使我们能够获得非 - 以前无法实现的人类和大型动物心的破坏性图像（亚毫米计） 解决。我们将使用新的亚毫米成像能力来获取对比度增强和扩散 - 猪和人类心脏的张量MRI，并从这些图像中开发出个性化模型。这些 高分辨率的前体模型将用于测试许多新型机械假设，以阐明如何 复杂的空间分布的结构和EP特征的治愈基础设施优先VT 穿过它。然后，我们将进行仿真和实验研究以建立关系 在亚毫米量表的基础架构和EP特征之间产生特定的VT 途径以及相应临床分辨率测量中的图像特征和电特征。 拟议研究的成功执行将提供对COM的签名的新理解 临床测量表现出与PLEX梗塞相关的微结构和EP重塑。新的 Insight将能够改善给定VT的最佳消融选项的确定，从而导致显着 疗法的效果进步。