The Maintenance of Human Atrial Fibrillation

人类心房颤动的维持

基本信息

批准号：
8706206
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 2014-08-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8706206
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 design heart rhythm interest minimally invasive novel patient oriented research programs public health relevance research study signal processing 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.

描述（由申请人提供）：心房颤动（AF）是美国最普遍的心律障碍，影响了可能引起中风，心pit，心力衰竭甚至死亡的2-5万个人。不幸的是，对AF的治疗是有限的。抗心律失常或速率控制药物的耐受性不佳，副作用频繁，不会降低中风风险。消融是一种新兴的最低侵入性疗法，引起了很大的关注，因为它可能会消除AF。不幸的是，AF消融在技术上具有挑战性，仅成功的50-70％（对于其他心律不齐而言> 90％）和严重的风险。这些局限性的主要原因是，人AF的机制尚不清楚，因此不能将消融针对它们。结果，AF消融是经验性的，并导致中庭大量破坏。在这项面向患者研究的中期指导奖中，申请人提出了针对临床医生科学家的指导培训计划，应用生物工程学原则来解决有关维持人AF的机械假设。从培训的角度来看，每个受训者都将获得申请人和跨学科研究委员会的持续指导，其中包括心律医学，生物工程，计算机建模和生物物理学专家。通过正式的合作，受训者还将能够培训细胞电生理学。还概述了结构化的教学训练。从科学上讲，我们的核心假设是人AF是由局部来源维持的，而不是广泛分散的机制（多波浪再入）。我们将在消融时在患者中创建房颤的房屋激活和恢复（复极化）的详细图，然后在近实时使用计算分析和药理学干预措施来研究维持AF的机制。个性化的计算机模型将是独一无二的，因为预测将直接针对同一患者观察到的AF进行测试，并且用于直接设计进一步的临床研究，并进行了差异。由于该项目是在消融时执行的，因此结果将很容易转化为练习。候选人的轨道记录是使用生物工程原理，信号处理和计算机模型来解决以心律不齐为中心的患者研究中的机械假设。他还拥有培训临床医生科学家的记录，他们继续从事以患者为导向的研究，其中许多人获得了校外资金。拟议的研究针对三个目的：1）确定局部来源是否维持人类AF； 2）确定复极化的替代剂，传导减慢还是解剖因素是解释对纤颤的混乱； 3）确定对潜在局部来源消融的AF的影响。成功完成我们的目标将导致对人AF的机械理解和消融方法的范式变化。受训者将在丰富的跨学科环境中接受培训，并在完成该计划后，将做好充分的准备，以从事以患者为导向的心律障碍研究的职业。