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，可能导致心跳加快、头晕、中风甚至死亡。标测技术的最新进展显示，绝大多数房颤患者都存在类似于电陀螺的螺旋波，这些螺旋波不会在整个心房腔中迁移，而是保持在一个有限且稳定的空间位置。目前尚不清楚的是，这些稳定的螺旋波是如何破坏并导致AF的，这限制了我们改善AF治疗的能力。该项目将测试新的假设，即心房组织的结构成分负责螺旋波的空间稳定性，而破坏是由发生在细胞水平上的心脏的“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绘图的理论/临床相结合的方法来解决这个假设。我们将1）使用计算机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解体; 3）创建患者特定的数字计算机模型，以测试房颤的可能原因。我们将在本项目中创建的患者特定的数字计算机模型将是最详细和临床-在该领域相关，并可以被其他人用来了解疾病，并帮助设计更好的治疗。该项目意义重大，因为它将建立人类房颤的新机制，可能导致消除AF的新疗法。在这个水平上了解AF也可能使药物开发和基因治疗更合理。该项目将在电生理研究期间对患者进行，以便其结果可以 直接转化为实践。

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.