Targeting the Arrhythmogenic Sources of Human Atrial Fibrillation

针对人类心房颤动的心律失常根源

基本信息

批准号：
9384067
负责人：
Vadim V Fedorov
金额：
$ 67.49万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9384067
关键词：
Ablation Adverse effects Affect American Anatomy Animal Model Arrhythmia Atrial Fibrillation Automobile Driving Characteristics Clinical Clinical Research Complex Computer Simulation Conflict (Psychology)Coronary Data Development Diabetes Mellitus Electrodes Epicardium Fingerprint Frequencies Gadolinium Goals Heart Heart Atrium Heart Diseases Heart failure Histology Hospitalization Human Hypertension Imagery Individual Investigation Knowledge Lead Lesion Location Magnetic Resonance Imaging Maintenance Maps Molecular Morbidity - disease rate Muscle Obesity Optics Pathway interactions Patients Procedures Recording of previous events Resolution Role Source Stroke Structure Surface Testing Thick Translational Research United States Variant aging population base experimental study human disease in vivo novel personalized medicine response spatiotemporal targeted treatment three dimensional structure

项目摘要

PROJECT SUMMARY Atrial fibrillation (AF), a leading cause of stroke, is an increasingly prevalent arrhythmia in the United States due to an aging population with predisposing conditions (e.g. heart failure, obesity, diabetes, high blood pressure, etc.). Although, there have been great technological advances in the treatment of AF, the current therapies still remain insufficient due to a limited understanding of the mechanisms that drive and maintain AF. Clinical studies currently lack reliable functional and structural mapping approaches necessary to resolve the detailed course of fast electrical activity during AF as a result of the highly complex patient-specific 3D structure of the human atria. Consequently, there remains a significant debate around the mechanism driving AF, the cause of these drivers, and how best to locate and treat these patient-specific drivers in patients with cardiac diseases. Therefore our study aims to develop a novel, paradigm-shifting framework that clearly identifies the exact electro-anatomical AF substrates, or AF driver “fingerprints”, for optimal AF treatment in humans. Our preliminary data led us to hypothesize that a limited number of patient-specific sustained reentry circuits through fibrotically-insulated muscular bundles within the 3D atrial wall are responsible for the maintenance of AF. We will test this hypothesis, directly in explanted human atria, by integrating high resolution simultaneous endo-epicardial and panoramic optical mapping, clinical multi-electrode mapping, 3D structural gadolinium-enhanced MRI, and 3D heart-specific computational models to define the spatiotemporal and structural fingerprints of AF drivers in the human atria. Accurately defining the specific atrial functional-structural fingerprints of AF drivers will allow us to test the novel Substrate Modulating Ablation of Reentrant Tracks (SMART), a minimally damaging, personalized treatment of AF. This translational research is a critical step toward the development of new patient-specific therapies whereby AF drivers can be accurately defined, targeted, and successfully treated to cure the most common arrhythmia in the United States.

项目概要心房颤动 (AF) 是中风的主要原因，在美国是一种日益流行的心律失常，原因是患有易感疾病（例如心力衰竭、肥胖、糖尿病、高血压、尽管房颤的治疗已经取得了巨大的技术进步，但目前的治疗方法仍然存在。由于对驱动和维持 AF 的机制了解有限，仍然不够。目前缺乏可靠的功能和结构映射必要的方法来解决详细过程由于人类心房高度复杂的患者特异性 3D 结构，导致 AF 期间出现快速电活动。经过测试，围绕驱动 AF 的机制、这些驱动因素的原因仍然存在重大争论，以及如何最好地找到和治疗患有心脏病的患者的这些特定驱动因素。研究旨在开发一种新颖的、范式转换的框架，该框架可以清楚地识别确切的电解剖学 AF 基板或 AF 驱动器“指纹”，用于实现人体最佳 AF 治疗我们的初步数据使我们得出结论。认为有限数量的患者特异性持续折返回路通过纤维化绝缘 3D 心房壁内的肌束负责维持 AF。我们将检验这一假设。通过集成高分辨率同步心外膜和全景，直接在移植的人类心房中光学测绘、临床多电极测绘、3D 结构钆增强 MRI 和 3D 心脏特异性计算模型来定义人类心房中 AF 驱动器的时空和结构指纹。准确定义 AF 驱动程序的特定心房功能结构指纹将使我们能够测试新颖的方法折返轨迹基质调制消融 (SMART)，一种损伤最小的个性化治疗这项转化研究是开发新的针对患者的疗法的关键一步。因此，可以准确定义、定位和成功治疗 AF 驱动因素，以治愈最常见的问题美国的心律失常。