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

项目总结

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.