The Maintenance of Human Atrial Fibrillation

人类心房颤动的维持

• 批准号: 8307838
• 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
• 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/8307838
• 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

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(申请人提供)：房颤(AF)是美国最常见的心脏节律紊乱，影响200万-500万人，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耐受性差，副作用频繁，不能降低中风风险。消融是一种新兴的微创治疗方法，因其可消除房颤而备受关注。不幸的是，房颤消融在技术上具有挑战性，成功率只有50%-70%(而其他心律失常的成功率为90%)，而且风险很大。这些局限性的一个主要原因是人类房颤的机制尚不清楚，因此不能针对它们进行消融。因此，房颤消融是经验性的，并导致对心房的广泛破坏。在这项以患者为中心的研究生涯中期指导奖中，申请者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有关维持人类房颤的机械性假设。从培训的角度来看，每名学员将得到申请者和一个由心律医学、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。通过正式的合作，学员还将能够接受细胞电生理学方面的培训。此外，还概述了结构化的教学培训。科学上，我们的中心假设是，人类房颤是由局部来源维持的，而不是广泛分散的机制(多子波再入)。我们将创建消融时房颤患者心房激活和恢复(复极)的详细地图，然后使用计算分析和药物干预近乎实时地研究维持房颤的机制。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的观察到的房颤进行测试，差异将用于直接设计进一步的临床研究。由于该项目是在消融时进行的，因此结果将很容易转化为实践。这位候选人在使用生物工程原理、信号处理和计算机模型来解决以心律失常为重点的患者导向研究中的机械假说方面有着良好的记录。他还拥有培训临床医生的记录，这些医生是继续从事以患者为导向的研究的科学家，其中许多人获得了外部资金。建议的研究有三个目标：1)确定局部消融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解释房颤的解离；3)确定潜在局部消融对房颤的影响。我们的目标的成功完成将导致对人类房颤的机械理解的范式改变，以及消融的方法。学员将在丰富的跨学科环境中接受培训，在完成这一课程后，将为开始以患者为导向的心律紊乱研究事业做好充分准备。 公共卫生相关性：纤颤(AF)是一个巨大的公共卫生问题，影响着200-500万美国人，导致中风、心跳加速和心力衰竭的发病率或死亡。通过这项以患者为中心的职业生涯中期指导奖，申请者将进行研究并培训初级医生-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，该项目可能会导致对房颤的理解和治疗的范式转变。