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）是最常见的心律障碍，影响了超过500万美国人，可能会导致跳过心跳，头晕，中风甚至死亡。映射技术的最新进展表明，绝大多数AF患者都存在类似于电旋转顶部的螺旋波，发现这些螺旋波不会在整个心房腔室中迁移，但仍位于密闭且稳定的空间位置。不清楚的是，这些稳定的螺旋波如何混乱并导致AF。该项目将检验新的假设，即心房组织的结构成分负责螺旋波的空间稳定性，并且混乱是由细胞水平上发生的心脏的“功能”特性引起的。我们将使用采用先进的多尺度计算技术和最先进的临床映射的合并理论/临床方法来解决这一假设。我们将1）确定使用计算模拟心脏组织的结构特性如何防止螺旋波在整个心房迁移； 2）确定药物如何影响螺旋波的迁移和混乱； 3）创建特定于患者的数字计算机模型以测试AF的可能原因。我们将在该项目中创建的特定于患者的数字计算机模型将是该领域最详细和临床上最详细的，并且可以被其他人用于理解该疾病并帮助设计更好的治疗。该项目之所以重要，是因为它将为人心房颤动建立新的机制，并有可能导致消除AF的新疗法。在此级别上了解AF也可能允许对药物开发和基因疗法采用更合理的方法。该项目将在电生理研究期间在患者中进行，以便其结果可以 直接翻译成练习。