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Multiscale Modeling of Clotting Risk in Atrial Fibrillation

心房颤动凝血风险的多尺度建模

基本信息

批准号：
10458660
负责人：
Boyce Eugene Griffith
金额：
$ 54.58万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
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/10458660
关键词：
Ablation Accounting Affect Anatomy Anticoagulants Anticoagulation Arrhythmia Atrial Fibrillation Biochemistry Biocompatible Materials Biophysics Blood Blood coagulation Blood flow Cardiac Cardiac ablation Clinical Clinical Data Coagulation Process Complex Computer Models Coupling Deep Vein Thrombosis Devices Disease Endothelium Exclusion FDA approved Functional disorder Goals Guidelines Heart Atrium Heart Valve Prosthesis Incidence Inflammation Innate Immune System Left Left atrial structure Liquid substance Measurement Mechanics Medical Medical Device Mitral Valve Modeling Monitor Morphology Operative Surgical Procedures Patients Pattern Performance Postoperative Period Pulmonary veins Reporting Research Resolution Risk Risk Assessment Role Stroke Structure Thromboembolism Thrombosis Thrombus Time United States Variant auricular appendage base clinical practice clinical risk clinically significant heart rhythm improved improved outcome indexing individualized medicine innovation medical complication multi-scale modeling novel personalized risk prediction pre-clinical predictive modeling programs risk stratification simulation stroke risk thrombogenesis tool tool development treatment guidelines ultrasound venous thromboembolism ventricular assist device

项目摘要

This project will develop clinically validated multiscale models of cardiac dynamics that integrate fluid dynamics, electromechanical coupling, and fluid-structure interaction (FSI) to simulate intracardiac flows and blood co-agulation in atrial fibrillation (AF). AF is the most common sustained arrhythmia in the U.S. and is associated with serious complications, including thromboembolism and stroke. Anticoagulation is commonly prescribed to patients who have an elevated stroke risk. However, current risk assessment indices, which lack individualization based upon atrial structure or function, classify most AF patients as being at intermediate risk. The core hypothesis of this research is that treatment guidelines using current risk assessment metrics result in many AF patients receiving unneeded anticoagulation and unnecessary monitoring for thrombosis. The long-term objective of this research is to develop new, broad-spectrum approaches to clotting risk assessment in AF that provide personalized risk prediction. The scientific premise of this proposal is that comprehensive models of atrial dysfunction will enable mechanistic studies of flow and clotting in AF that will ultimately facilitate individualized treatment. In AF, most clinically significant thrombi form in the left atrial appendage (LAA). The anatomy of the LAA is extremely heterogeneous, and although there is an emerging appreciation that LAA anatomy affects clotting risk, anatomy is not considered in current guidelines. Computer models provide ideal platforms for studying the impact of structural and functional variations on LAA flow patterns, but most existing cardiac fluid dynamics models focus on the ventricles. Further, no existing FSI model of the atria includes a detailed description of the LAA, which, like the ventricles and unlike the main LA cavity, is highly trabeculated. A key innovation of this project is that it will develop clinically validated FSI models of cardiac flow in patient-specific descriptions of LA anatomies, including realistic models of the LAA. These models will be extended to include biophysically detailed models of coagulation dynamics and clot transport. This project aims both to establish these models and also to apply them to study flows and clotting dynamics in two therapies for AF: (1) percutaneous LAA exclusion via the WATCHMAN device and (2) electrically isolating the LAA in catheter ablation therapy. In the case of LAA exclusion, the incidence of device-associated thrombosis is 3.4%; consequently, post-operative anticoagulation therapy is currently used in all patients receiving these devices. Electrical isolation of the LAA is rarely performed because of concerns about its effect on systolic flow and stroke risk, and the inability to identify patients who would benefit. The core modeling approaches developed in this project can also be deployed to simulate thrombogenesis in a range of significant medical conditions (venous thromboembolism, deep vein thrombosis), medical devices (prosthetic heart valves, ventricular assist devices, IVC filters), and novel biomaterials. Ultimately, models using this platform are expected to be submitted to the FDA Medical Device Development Tools program as non-clinical assessment models to predict pre-clinical device performance in regulatory submissions.

该项目将开发临床验证的心脏动力学多尺度模型，将流体动力学、