The Maintenance of Human Atrial Fibrillation

 描述(申请人提供)：人体心房颤动的维护项目摘要。房颤(AF)是最常见的心律失常，影响着200-500万美国人，可能会导致心跳加速、头晕、中风甚至死亡。不幸的是，房颤的治疗是有限的。开发更好的房颤治疗方法的主要缺点之一是，我们对房颤的原因(其‘机制’)的了解并不清楚。 这一更新概述了申请者的职业发展计划、年轻临床医生-科学家的指导培训以及以患者为中心的房颤机械性研究计划建立在上一个周期的发现基础上，即人类房颤通常不是随机的，而是由少量随时间稳定的转子(类似于电动旋转陀螺)或焦点节拍形式的“源”维持(驱动)。来源可能位于每个患者不同的心脏区域(心房或顶室)，通常远离医生目前应用烧灼治疗(消融)的地方。在本项目中，我们将研究1) 在这些转子来源之上的触发部位(肺静脉)消融可以获得多少额外的好处；2)转子实际上如何导致无序的节律，而不仅仅是简单的有组织的回路；3)这一过程是否会因心房的结构异常而改变。我们将在临床试验中实现这些目标，通过对房颤进行详细的记录，使用生物工程方法和整合成像。这些针对患者的分析将是该领域最详细和最具临床相关性的分析之一，并将为未来的假设检验和临床试验提供一个平台。 这个项目意义重大，因为它测试了最近发现的房颤转子的新疗法相对于当前护理标准的成功，因为它研究了导致人类心脏颤动的基本机制，还因为它还测试了新的成像策略。该项目将在电生理学研究期间在房颤患者和数量有限的非房颤患者中进行，以便其结果可以直接转化为实践。这种方法 也可能允许对药物开发和基因治疗采取更合理的一般方法。

 DESCRIPTION (provided by applicant): The Maintenance of Human Atrial Fibrillation Project Summary. Atrial fibrillation (AF) is the most common heart rhythm disorder, affecting 2-5 million Americans in whom it may cause skipped heart beats, dizziness, stroke and even death. Unfortunately, therapy for AF is limited. One of the major drawbacks in developing better therapy for AF is that our understanding of what causes AF (its `mechanisms') is not clear. This renewal outlines a program of career development for the applicant, of Mentored training for young clinician-scientists, and of mechanistic patient-oriented research in atrial fibrillation The Research Plan builds upon discoveries in the last cycle, that human AF is often not random, but instead maintained (driven) by a small number of `sources' in the form of rotors (akin to electrical spinning tops) or focal beats, that are stable over time. Sources may lie in regions of the heart (the atria, or top chambers) that are different in each patient, often away from where physicians currently apply cautery therapy (ablation). In this project, we will study 1) how much additional benefit is achieved by ablating at trigger sites (at the pulmonary veins) over and above these rotor source; 2) how rotors actually cause disorganized rhythms, and not just simple organized circuits; 3) whether this process is altered by structural abnormalities in the atria. We will pursue these aims in a clinical trial, by making detailed recordings of AF, usin bioengineering methods and by integrating imaging. These patient-specific analyses will be among the most detailed and clinically-relevant in the field, and will form a platform for future hypothesis testing and clinical trials. This project is significant because it tests the success of novel therapy at recently discovered AF rotors against current standard-of-care, because it studies the fundamental mechanisms that cause cardiac fibrillation in humans, and because it also tests novel imaging strategies. This project will be performed in patients with AF and a limited number of patients without AF, during electrophysiologic study, so that its results can be translated directly to practice. This approach may also allow a more rational general approach to drug development and gene therapy.