The Dynamics of Human Atrial Fibrillation

描述(申请人提供)：房颤(AF)是最常见的心脏节律紊乱，影响200-500万美国人，可能导致心跳加速、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。这个更新项目建立在该小组在上一次资助期间的发现之上，即人类房颤不是随机或混乱的，而是经常由少量的以转子(类似于电子旋转顶)或焦点节拍的形式维持(驱动)的，随着时间的推移是稳定的。来源可能位于每个患者不同的心脏区域(心房或顶室)，通常远离医生通常针对烧灼治疗(消融)的地方。在这个项目中，我们将研究1)单独消融旋转源和焦点源(驱动房颤)的有效性；2)消融如何改变转子、肺静脉附近的触发部位或其他机制；3)一些患者消融后可能复发的房颤机制。我们将通过记录房颤的详细地图，并在每个主题中研究房颤的几种主要可能机制来实现这些目标。这些研究将包括对心房组织功能的详细记录、对房颤的数学分析、消融后患者的详细随访以及对可能复发的房颤患者的重复研究。我们将在这个项目中进行的针对患者的分析将是该领域中最详细和最具临床相关性的分析之一，将被用来了解疾病并帮助设计更好的治疗方法。这个项目意义重大，因为它将定义最近发现的房颤新机制治疗的成功，在这种治疗不成功的情况下，我们将研究原因。通过这种方式，我们将开发一种方法来更好地确定每个患者发生房颤的原因(机制)。该项目将在电生理研究期间在房颤患者中进行，因此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): 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 project builds on discoveries by this group in the last funding period that human AF is not random or chaotic, but instead is often 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 typically target cautery therapy (ablation). In this project, we will study 1) the effectiveness of ablation of rotos and focal sources alone (that drive AF); 2) how ablation alters rotors, trigger sites near the pulmonary veins, or other mechanisms; 3) the mechanisms for AF that may recur in some patients after ablation. We will pursue these aims by recording detailed maps of AF and studying several major possible mechanisms for AF in each subject. These studies will include detailed recordings of atrial tissue function, mathematical analyses of AF, detailed follow-up of patients after ablation and repeat study in patients in whom AF may recur. The patient-specific analyses that we will perform in this project will be among the most detailed and clinically-relevant in the field, and will be used to understand the disease and to help design better therapy. This project is significant because it will define the success of therapy at recently discovered novel mechanisms for AF and, in cases when such therapy is unsuccessful, we will study why. In this way, we will develop an approach to better define the causes (mechanisms) for AF in each patient. This project will be performed in patients with 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.