Infarct-related Ventricular Tachycardia Mechanisms: From Micro to Clinical

项目摘要 室性心动过速（VT）是一种危及生命的快心律，常发生于心肌梗死患者， 心肌梗塞，导致心脏性猝死。基于导管的消融提供了永久治愈的可能性 通过中断VT折返电路。不幸的是，用消融术消除梗死相关性室性心动过速已经达到了 只有适度的成功，50- 88%。这源于与当前VT电标测相关的局限性 以及使用临床VT图来识别用于消融的目标位置。采用新的战略， 提供对梗死区复杂现象的全面理解，以及它们如何相互关联 临床措施是一个追求最重要的临床意义，这将导致显着改善， 确定梗死相关VT的最佳消融靶点。 本项目的总体目标是应用新的成像和建模方法， 全面了解复杂的微观结构和电生理（EP）因素 在已愈合的梗死区建立特定的VT通路，并确定这些因素如何影响患者的预后。 在临床影像学和EP测量中得到反映。我们实现这一目标的能力源于新的 我们的团队的发展，例如发明了一种新的MRI脉冲序列，使我们能够获得非- 整个人类和大型动物心脏的破坏性图像，以前无法达到（亚毫米） 分辨率我们将使用我们新的亚毫米成像能力来获取对比度增强和扩散- 张量MRI的猪和人类心脏离体和开发个性化的模型，从这些图像。这些 高分辨率离体模型将用于测试许多新的机制假说，阐明如何 已愈合梗死的复杂空间分布结构和EP特征建立了优先VT 然后，我们将进行模拟和实验研究，以建立关系 在亚毫米尺度上，梗死结构和EP特征之间存在差异， 路径，以及相应的临床分辨率测量中的图像特征和电签名。 成功执行拟议的研究将提供一个新的理解的签名的com- 复杂梗死相关的微结构和EP重塑，因为它们在临床测量中表现出来。新 洞察力将能够更好地确定给定VT的最佳消融选项， 提高治疗效果。

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.