The Maintenance of Human Atrial Fibrillation

 描述（由申请人提供）：人类房颤维持项目总结。心房颤动（AF）是最常见的心律失常，影响2-5百万美国人，可能导致心跳加快，头晕，中风甚至死亡。不幸的是，房颤的治疗方法有限。开发更好的AF治疗方法的主要缺点之一是，我们对AF的病因（其“机制”）的理解尚不清楚。 该更新概述了申请人的职业发展计划，年轻临床医生-科学家的指导培训计划，以及房颤中以患者为导向的机械研究计划。研究计划建立在上一个周期的发现基础上，即人类AF通常不是随机的，而是由少量转子形式的“源”维持（驱动）（类似于电旋转陀螺）或随时间稳定的局灶性搏动。来源可能位于心脏的区域（心房或顶部腔室），每个患者的情况都不同，通常远离医生目前应用烧灼疗法（消融）的地方。在这个项目中，我们将研究1） 通过在这些转子源之上的触发部位（在肺静脉处）进行消融获得了多少额外的益处; 2）转子实际上如何引起紊乱的节律，而不仅仅是简单的有组织的回路; 3）该过程是否被心房中的结构异常改变。我们将在临床试验中实现这些目标，通过使用生物工程方法和整合成像技术对AF进行详细记录。这些患者特异性分析将是该领域最详细和临床相关的分析之一，并将为未来的假设检验和临床试验提供平台。 该项目意义重大，因为它测试了新疗法在最近发现的AF转子上的成功，因为它研究了导致人类心脏颤动的基本机制，并且还测试了新的成像策略。该项目将在电生理研究期间对房颤患者和少数非房颤患者进行，以便其结果可以直接转化为实践。这种方法 也可能为药物开发和基因治疗提供更合理的一般方法。

 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.