Integrated functional and structural mapping for targeting substrates of reentrant atrial fibrillation drivers in the human heart

项目总结 房颤是中风的主要原因之一，在美国是一种日益普遍的心律失常 由于人口老龄化和易患疾病(如心力衰竭、肥胖、糖尿病、高血压病) 压力等)。虽然，巨大的技术进步将房颤治疗带入了个性化时代 策略，目前的治疗方法仍然不足，因为对机制的了解有限， 驾驶和维护房颤。临床研究目前缺乏可靠的功能和结构图谱方法 有必要解决由于高度复杂的房颤期间快速电活动的详细过程 特定于患者的人体心房的3D结构。因此，我们的研究旨在通过以下方式改善房颤的治疗 揭示了高分辨率体外和体内标测所看到的准确的电解剖房颤底物。 我们的初步数据让我们假设，有限数量的患者特有的持续折返回路 通过纤维隔绝的3D房壁内的肌束负责维持 自动对焦。我们将直接在移植的人体心房中，通过整合高分辨率的同步信号来检验这一假说。 心内膜和全景光学标测，临床多电极标测，3D结构对比- 增强MRI以确定房颤驾驶员在人类心房的时空和结构底物。 此外，我们将确定整合功能和结构映射的可行性，以改进 有针对性的房颤驱动消融治疗。准确确定特定的心房功能-结构底物 房颤司机通过集成功能和结构映射将实现高效、个性化的治疗 用于房颤消融。这项转译研究是开发新的针对患者的关键一步 可以准确定义、有针对性并成功治疗房颤司机的疗法，以治愈最 美国常见的心律失常。

PROJECT SUMMARY Atrial fibrillation (AF), a leading cause of stroke, is an increasingly prevalent arrhythmia in the United States due to an aging population with predisposing conditions (e.g. heart failure, obesity, diabetes, high blood pressure, etc.). Although, great technological advances have brought AF treatment into an age of personalized strategies, current therapies still remain insufficient due to a limited understanding of the mechanisms that drive and maintain AF. Clinical studies currently lack reliable functional and structural mapping approaches necessary to resolve the detailed course of fast electrical activity during AF as a result of the highly complex patient-specific 3D structure of the human atria. Therefore, our study aims to improve AF treatment by revealing the exact electro-anatomical AF substrates seen by both high-resolution ex vivo and in vivo mapping. Our preliminary data led us to hypothesize that a limited number of patient-specific sustained reentry circuits through fibrotically-insulated muscular bundles within the 3D atrial wall are responsible for the maintenance of AF. We will test this hypothesis, directly in explanted human atria, by integrating high resolution simultaneous endo-epicardial and panoramic optical mapping, clinical multi-electrode mapping, and 3D structural contrast- enhanced MRI to define the spatiotemporal and structural substrates of AF drivers in the human atria. Furthermore, we will determine the feasibility of integrating functional and structural mapping to improve targeted AF driver ablation in patients. Accurately defining the specific atrial functional-structural substrates of AF drivers by integrating functional and structural mapping will allow a highly efficient, personalized treatment for AF ablation. This translational research is a critical step toward the development of new patient-specific therapies whereby AF drivers can be accurately defined, targeted, and successfully treated to cure the most common arrhythmia in the United States.