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Simulation Guidance of Ablation Therapy for Persistent Atrial Fibrillation

持续性心房颤动消融治疗模拟指导

基本信息

批准号：
10213120
负责人：
HUGH G CALKINS
金额：
$ 74.65万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10213120
关键词：
Ablation Address American Animal Model Arrhythmia Atrial Fibrillation Behavior Behavioral Biological Canis familiaris Cardiac ablation Catheters Cells Clinical Clinical Research Computer Models Diagnosis Electrophysiology (science)Ensure Environment Fibrosis Freedom Gadolinium Geometry Health Care Costs Healthcare Heart Atrium Heart Diseases Hemorrhage Histology Hour Human Image Individual Lesion MRI Scans Magnetic Resonance Imaging Measurement Medical Economics Methodology Modeling Molecular Morbidity - disease rate Nature Navigation System Organ Outcome Patient Simulation Patients Pharmaceutical Preparations Pilot Projects Population Procedures Radiation Recording of previous events Recurrence Risk Site Structure Testing Tissues Treatment Efficacy advanced simulation base clinically significant contrast enhanced economic impact effective therapy experimental study global health improved in silico mortality multi-scale modeling novel novel strategies personalized predictions prospective response simulation success treatment optimization

项目摘要

PROJECT SUMMARY This application is in response to PAR-15-085: Predictive Multiscale Models for Biomedical, Biological, Behavioral, Environmental and Clinical Research (Interagency U01), with Cutting Edge Challenge: Predictive multiscale models to improve clinical workflow, standard operating procedures, patient-specific modeling for diagnosis and therapy planning. Atrial ﬁbrillation (AF) is the most prevalent sustained cardiac arrhythmia, leading to morbidity and mortality in 1-2% of the population and contributing signiﬁcantly to global health care costs. For patients in whom AF can- not be treated by drugs, the recommended therapy is catheter-based ablation to isolate arrhythmia triggers and eliminate the substrate for arrhythmia perpetuation. However, outcomes of the procedure are poor ( 50% suc- cess rate) in patients with persistent AF (PsAF) due to the presence of extensive atrial ﬁbrosis, which confounds ablation strategies. There is an urgent need for new approaches that can result in swift and accurate iden- tiﬁcation of optimal ablation targets for PsAF and thereby improve the efﬁcacy of and increase the tolerance for the therapy, as well as reduce post-procedure complications and repeated ablations. The overall objective of this application is to develop and validate a novel personalized multiscale modeling strategy for determining the optimal targets for catheter ablation of the fibrotic substrate in patients with PsAF. We propose to develop and validate atrial models reconstructed from MRI images of pa- tients with PsAF and fibrotic remodeling. The models will integrate mechanistically functions from the molecular level to the electrophysiological interactions in the intact organ. We will parametrize and validate the simula- tion approach with experimental measurements in explanted human atria and animal models. We will use the validated personalized modeling strategy to determine, in retrospective patient studies, what constitutes a set of optimal ablation lesions that terminate AF with the least likelihood of recurrence. The project will culminate with a pilot prospective patient study, where AF ablation will be executed directly at the simulation-predicted targets. Successful execution of the proposed studies will pave the way for a major paradigm shift in the clinical procedure of AF ablation in patients with fibrotic remodeling, resulting in a dramatic improvement in the efficacy of the therapy. Importantly, completion of this project will result in a major leap forward in the integration of computational modeling in the diagnosis and treatment of cardiac disease.

项目总结