Patient-directed Computational Analysis of Atrial Fibrillation

描述（由申请人提供）：心房颤动（AF）是最常见的心律失常，影响超过500万美国人，可能导致心跳跳过、头晕、中风甚至死亡。制图技术的最新进展表明，螺旋波，类似于电旋顶，存在于绝大多数房颤患者。结果发现，这些螺旋波不会在心房内迁移，而是停留在一个有限的、稳定的空间位置。尚不清楚的是，这些稳定的螺旋波是如何组织紊乱并导致心房颤动的，这限制了我们改善心房颤动治疗的能力。该项目将测试心房组织的结构成分负责螺旋波的空间稳定性，而这种紊乱是由细胞水平上发生的心脏的“功能”特性引起的。我们将采用先进的多尺度计算技术和最先进的临床制图相结合的理论/临床方法来解决这一假设。我们将1)使用计算模拟确定心脏组织的结构特性如何阻止螺旋波在整个心房中迁移；2)确定药物如何影响螺旋波的迁移和破坏；3)创建患者特异性数字计算机模型来测试房颤的可能原因。我们将在这个项目中创建的患者特异性数字计算机模型将是该领域最详细和临床相关的模型之一，并且可以被其他人用来了解疾病并帮助设计更好的治疗方法。该项目意义重大，因为它将建立人类心房颤动的新机制，可能导致消除房颤的新疗法。在这个水平上了解房颤也可能为药物开发和基因治疗提供更合理的方法。本项目将在患者电生理研究期间进行，使其结果可以

DESCRIPTION (provided by applicant): Atrial fibrillation (AF) is the most common heart rhythm disorder, affecting over 5 million Americans in whom it may cause skipped heart beats, dizziness, stroke and even death. Recent advances in mapping techniques have revealed that spiral waves, similar to electrical spinning tops, are present in the vast majority of AF patients.It was found that these spiral waves do not migrate throughout the atrial chambers but remain in a confined and stable spatial location. What is not clear, and limiting our ability to improve therap for AF, is how these stable spiral waves disorganize and cause AF. This project will test the novel hypothesis that structural components of the atrial tissue are responsible for the spatial stability of the spiral waves and that the disorganization is caused by 'functional' properties of the heart that occur at the level of cells. We will address this hypothesis using a combined theoretical/clinical approach that employs advanced multiscale computational techniques and state-of-the-art clinical mapping. We will 1) determine using computational simulations how structural properties of heart tissue can prevent spiral waves from migrating throughout the atria; 2) determine how drugs affect the migration and disorganization of spiral waves; 3) create patient-specific digital computer models to test possible causes of AF. The patient-specific digital computer models that we will create in this project will be among the most detailed and clinically-relevant in the field, and can be used by others to understand the disease and help design better therapy. This project is significant because it will establish new mechanisms for human atrial fibrillation, potentially resulting in novel therapies to eliminate AF. Understanding AF at this level may also allow a more rational approach to drug development and gene therapy. This project will be performed in patients during electrophysiologic study, so that its results can be translated directly to practice.