Patient-directed Computational Analysis of Atrial Fibrillation

患者导向的心房颤动计算分析

• 批准号: 8817196
• 负责人: WOUTER-JAN RAPPEL
• 金额: $ 38.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-12 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8817196
• 关键词: Ablation; Action Potentials; Address; Advanced Development; Affect; American; Area; Atrial Fibrillation; Attenuated; Behavior; Cardiac; Cells; Cessation of life; Clinical; Computational Technique; Computer Analysis; Computer Simulation; Dependence; Digital Computers; Disease; Dizziness; Ectopic beats; Elements; Exhibits; Geometry; Heart; Heart Atrium; Heart failure; Heterogeneity; Human; Intervention; Link; Location; Maps; Modeling; Motion; Organ; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Procainamide; Property; Public Health; Pulmonary veins; Reporting; Research; Resolution; Series; Source; Stroke; Structure; Surface; Techniques; Testing; Therapeutic; Tissues; Translating; clinically relevant; design; drug development; effective therapy; gene therapy; heart rhythm; ibutilide; improved; indexing; migration; mortality; novel; prevent; public health relevance; spatiotemporal; success

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.

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，可能导致心跳过速、头晕、中风甚至死亡。测绘技术的最新进展表明，绝大多数 AF 患者体内都存在类似于电动陀螺的螺旋波。研究发现，这些螺旋波不会在整个心房中迁移，而是保留在有限且稳定的空间位置。目前尚不清楚的是，这些稳定的螺旋波如何瓦解并导致房颤，这也限制了我们改进房颤治疗的能力。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，并且这种混乱是由细胞水平上发生的心脏“功能”特性引起的。我们将采用理论/临床相结合的方法来解决这一假设，该方法采用先进的多尺度计算技术和最先进的临床绘图。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混乱； 3) 创建患者特定的数字计算机模型来测试 AF 的可能原因。我们将在该项目中创建的患者特定数字计算机模型将是该领域最详细且与临床相关的模型之一，其他人可以使用它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，可能会产生消除房颤的新疗法。在这个层面上了解 AF 也可能为药物开发和基因治疗提供更合理的方法。该项目将在电生理学研究期间在患者身上进行，以便其结果可以 直接转化为实践。