The Maintenance of Human Atrial Fibrillation

人类心房颤动的维持

基本信息

批准号：
8134287
负责人：
Sanjiv M Narayan
金额：
$ 18.89万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8134287
关键词：
Ablation Action Potentials Activation Analysis Address Adverse effects Affect American Anatomy Animal Model Anti-Arrhythmia Agents Arrhythmia Atrial Fibrillation Atrial Tachycardia Attention Award Basic Science Biological Biomedical Engineering Cessation of life Clinical Clinical Research Clinical Sciences Collaborations Computer Analysis Computer Simulation Data Dementia Diagnosis Disease Drug Controls Electrodes Electrophysiology (science)Environment Extramural Activities Funding Glossary Heart Heart Atrium Heart failure Hospitalization Human Individual Interdisciplinary Study Intervention Junior Physician Lead Lesion Location Maintenance Maps Medical Medicine Mentors Methods Morbidity - disease rate Operative Surgical Procedures Palpitations Patients Physics Pilot Projects Procedures Public Health Pulmonary veins Quality of life Receiver Operating Characteristics Recovery Research Personnel Research Training Resources Risk Role Scientist Secure Source Stroke Structure Surgical incisions Testing Time Tissues Training Training Programs Translating Variant X-Ray Computed Tomography base career clinically significant computerized data processing design heart rhythm interest minimally invasive novel patient oriented research programs public health relevance research study success

项目摘要

DESCRIPTION (provided by applicant): Atrial fibrillation (AF) is the most prevalent heart rhythm disorder in the U.S., affecting 2-5 million individuals in whom it may cause stroke, palpitations, heart failure, and even death. Unfortunately, therapy for AF is limited. Anti-arrhythmic or rate-controlling drugs are poorly tolerated, with frequent side effects and do not reduce stroke risk. Ablation is an emerging minimally invasive therapy that has attracted considerable attention because it may eliminate AF. Unfortunately, AF ablation is technically challenging, with a success of only 50-70 % (versus >90% for other arrhythmias), and serious risks. A major cause of these limitations is that the mechanisms for human AF are not known and thus ablation cannot be directed to them. As a result, AF ablation is empiric and results in extensive destruction of the atrium. In this Mid-Career Mentoring Award in Patient Oriented Research, the applicant proposes a mentored training program for clinician-scientists, applying bioengineering principles to address mechanistic hypotheses on the maintenance of human AF. From a training perspective, each mentee will receive continuous mentoring by the applicant and an interdisciplinary research committee comprising experts in heart rhythm medicine, bioengineering, computer modeling and biological physics. Through formalized collaborations, mentees will also be able to train in cellular electrophysiology. Structured didactic training is also outlined. Scientifically, our central hypothesis is that human AF is maintained by localized sources, as opposed to widely dispersed mechanisms (multi-wavelet reentry). We will create detailed maps of atrial activation and recovery (repolarization) in AF in patients at ablation, and then use computational analysis and pharmacologic interventions in near-real-time to study mechanisms that maintain AF. Personalized computer models will be unique in that predictions will be tested directly against observed AF in the same patient, with discrepancies used to directly design further clinical studies. Because the project is performed at ablation, results will be easily translated to practice. The candidate has a track-record of using bioengineering principles, signal processing and computer models to address mechanistic hypotheses in arrhythmia-focused patient oriented research. He also has a track record of training clinician-scientists who continue to pursue patient oriented research, many of whom have secured extramural funding. Proposed studies address three Aims: 1) To determine if localized sources maintain human AF; 2) To determine if repolarization alternant, conduction slowing or anatomic factors explain disorganization to fibrillation; 3) to determine the impact on AF of ablating at potential localized sources. Successful completion of our Aims will lead to a paradigm-change in the mechanistic understanding of human AF, and approaches to its ablation. Mentees will be trained in a rich interdisciplinary environment and, on completing this program, will be well prepared to embark upon careers in patient-oriented research in heart rhythm disorders. PUBLIC HEALTH RELEVANCE: fibrillation (AF) is an enormous public health problem that affects 2-5 million Americans, causing morbidity or death from stroke, rapid heartbeats and heart failure. Through this Mid-Career Mentoring Award in Patient Oriented Research, the applicant will perform research and train junior physician-researchers to better understand AF, and determine if abnormal activity in small regions or more widespread regions of the heart cause AF. By performing these studies in patients during clinical procedures, this project may lead to a paradigm-shift in understanding and treating AF.

描述（由申请人提供）：心房颤动 (AF) 是美国最常见的心律失常，影响 2-500 万人，可能导致中风、心悸、心力衰竭，甚至死亡。不幸的是，房颤的治疗是有限的。抗心律失常或心率控制药物的耐受性较差，经常出现副作用，并且不能降低中风风险。消融是一种新兴的微创疗法，因其可以消除房颤而引起了相当大的关注。不幸的是，房颤消融在技术上具有挑战性，成功率仅为 50-70%（而其他心律失常的成功率>90%），且风险严重。这些限制的主要原因是人类 AF 的机制尚不清楚，因此无法针对它们进行消融。因此，房颤消融是经验性的，会导致心房的广泛破坏。在以患者为导向的研究中的职业生涯中期指导奖中，申请人提出了一项针对临床医生科学家的指导培训计划，应用生物工程原理来解决人类房颤维持的机制假设。从培训的角度来看，每位学员都将得到申请人和由心律医学、生物工程、计算机建模和生物物理学专家组成的跨学科研究委员会的持续指导。通过正式合作，学员还将能够接受细胞电生理学方面的培训。还概述了结构化的教学培训。从科学角度来说，我们的中心假设是，人类 AF 是由局部来源维持的，而不是广泛分散的机制（多小波折返）。我们将创建消融患者 AF 心房激活和恢复（复极）的详细图谱，然后近乎实时地使用计算分析和药物干预来研究维持 AF 的机制。个性化计算机模型的独特之处在于，将直接根据同一患者观察到的 AF 来测试预测，并将差异用于直接设计进一步的临床研究。由于该项目是在消融过程中进行的，因此结果很容易转化为实践。该候选人拥有使用生物工程原理、信号处理和计算机模型来解决以心律失常为中心的以患者为中心的研究中的机制假设的记录。他还拥有培训临床医生科学家的记录，这些临床医生科学家继续从事以患者为导向的研究，其中许多人获得了校外资助。拟议的研究涉及三个目标：1）确定局部来源是否维持人类房颤； 2) 确定复极交替、传导减慢或解剖因素是否可以解释纤维颤动的紊乱； 3) 确定潜在局部源消融对 AF 的影响。成功完成我们的目标将导致对人类房颤机制的理解及其消融方法的范式改变。学员将在丰富的跨学科环境中接受培训，完成该计划后，将为从事以患者为导向的心律失常研究职业做好充分准备。公共卫生相关性：颤动 (AF) 是一个巨大的公共卫生问题，影响着 2-500 万美国人，导致中风、心跳加快和心力衰竭导致发病或死亡。通过这项以患者为导向的研究中的职业生涯中期指导奖，申请人将进行研究并培训初级医师研究人员，以更好地了解房颤，并确定心脏小区域或更广泛区域的异常活动是否会导致房颤。通过在临床过程中对患者进行这些研究，该项目可能会导致理解和治疗 AF 的范式转变。