Multiscale Modeling of Clotting Risk in Atrial Fibrillation

心房颤动凝血风险的多尺度建模

• 批准号: 10226154
• 负责人: Boyce Eugene Griffith
• 金额: $ 55.16万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10226154
• 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; Ultrasonography; 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; venous thromboembolism; ventricular assist device

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.

该项目将开发经临床验证的心脏动力学多尺度模型，以整合流体动力学， 机电耦合和流体结构相互作用（FSI），以模拟心脏内流和血液 心房颤动（AF）的凝聚。 AF是美国最常见的持续性心律失常，与之相关 严重的并发症，包括血栓栓塞和中风。通常规定 中风风险升高的患者。但是，当前缺乏个性化的风险评估指数 基于心房结构或功能，将大多数AF患者分类为中间风险。核心 这项研究的假设是使用当前风险评估指标的治疗指南导致许多AF患者 接受不需要的抗凝和不必要的血栓形成监测。这个长期目标 研究是为了在提供的AF中开发新的，广泛的方法来凝结风险评估 个性化风险预测。该提议的科学前提是，房功能障碍的全面模型将 对AF中的流量和凝结的机理研究最终将促进个性化治疗。 在AF中，左心附属物（LAA）中大多数临床上具有重要意义的血栓形式。 LAA的解剖结构是 极其异质，尽管有一种新兴的认识，即LAA解剖学会影响凝结风险，但 目前的指南中未考虑解剖结构。计算机模型为研究影响提供了理想的平台 LAA流量模式上的结构和功能变化，但大多数现有的心脏流体动力学模型聚焦 在心室。此外，没有现有的中心FSI模型包括对LAA的详细描述，就像 与主腔不同的心室和不同的腔是高度小径。该项目的关键创新是它将 在患者特定的LA解剖学描述中开发经过临床验证的FSI心脏流动模型，包括 LAA的现实模型。这些模型将扩展到包括生物物理详细的凝结模型 动力和凝块运输。该项目旨在建立这些模型，并应用它们进行研究 AF的两种疗法中的流量和凝结动力学 （2）在导管消融疗法中进行电隔离LAA。在LAA排除的情况下，发病率 设备相关的血栓形成为3.4％；因此，目前使用术后抗凝治疗 所有接收这些设备的患者。由于担心 它对收缩流和中风风险的影响，以及无法识别受益的患者。 该项目中开发的核心建模方法也可以部署以模拟血栓形成 在一系列重要的医疗状况（静脉血栓栓塞，深静脉血栓形成）中，医疗设备 （假肢心脏瓣膜，心室辅助设备，IVC过滤器）和新型生物材料。最终，使用模型 预计该平台将作为非临床的FDA医疗设备开发工具计划提交 评估模型以预测监管提交中的临床前装置性能。