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

项目摘要 心房颤动（AF）是中风的主要原因，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）， 压力等）。虽然，巨大的技术进步使AF治疗进入了个性化的时代， 虽然目前的治疗策略仍然不足，但由于对 临床研究目前缺乏可靠的功能和结构映射方法 这是解决AF期间快速电活动的详细过程所必需的，这是由于高度复杂的 人类心房的患者特异性3D结构。因此，我们的研究旨在通过以下方法改善AF治疗： 揭示了通过高分辨率离体和体内标测观察到的精确电解剖AF基质。 我们的初步数据使我们假设，有限数量的患者特异性持续折返回路 通过3D心房壁内的纤维化绝缘肌束负责维持 af.我们将测试这一假设，直接在人类心房，通过整合高分辨率同步， 心内膜-外膜和全景光学标测、临床多电极标测和3D结构对比- 增强MRI以定义人类心房中AF驱动器的时空和结构基底。 此外，我们将确定整合功能和结构映射的可行性， 患者的靶向AF驱动消融。准确定义特定的心房功能-结构基质， 通过整合功能和结构映射的AF驱动程序将允许高效，个性化的治疗 用于房颤消融。这项转化研究是开发新的患者特异性药物的关键一步。 AF驱动因素可被准确定义、靶向并成功治疗， 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.