Development of a novel computational framework to support therapeutic-planning in selecting the optimal thromboembolic prevention treatment for AF

1)对研究背景的简要描述，包括潜在的影响房颤(房颤)是最常见的心律失常，其特点是心跳迅速且杂乱无章。它影响2-3%的人口，65岁的人患病率上升到9%。它是血栓事件(即中风和血管性痴呆)的主要原因，预计到2035年其发病率将增加一倍以上。据估计，在房颤下，90%的血栓起源于左心耳(LAA)，这是一个远离左房(LA)的2-4厘米的复杂形状突起。最常见的预防房颤患者血栓的治疗方法是口服抗凝；然而，由于相关的终生出血风险、费用和几种需要频繁实验室监测的食物/药物相互作用，这在高达44%的房颤患者中是禁忌。或者，可以应用外部缝线结扎术--例如LARIAT圈套装置(SentreHeart)--或自闭式夹闭装置--例如AtriClip LAA隔绝系统(AtriCure)--进行外科左心耳隔绝术。经皮LAA闭塞设备克服了侵入性手术的缺点，基于支持聚酯闭塞补片的自我膨胀的镍钛框架。两种最常见的解决方案是Watchman FLX(波士顿科学公司)和Amplatzer Amulet(雅培公司)。由于所有这些选项都存在重大缺陷，因此开发一种新的方法来识别哪些患者组的血栓栓子事件的风险可以证明特定的治疗方法是合理的，以及对每个受试者来说最安全和最有效的治疗方法是至关重要的。2)目的和目的总体项目目标是开发一个新的计算框架来支持临床决策，为每个房颤患者选择最佳的血栓预防治疗，识别无法在体内测量的流体动力学参数。1.对房颤患者的活体医学图像进行分析和分割，获得房颤患者左房的三维形态/动态特征。建立房颤人群的流体结构相互作用(FSI)计算模型，包括LAA/LA解剖特征，研究不同LAA形态与血流动力学之间的关系，以及捕捉临床诊断中无法获得的LAA形态。开发主要血栓预防治疗(即抗凝剂和LAA排除器和闭塞装置)的模型，允许评估解剖-治疗相互作用和流体-动力学条件。3)研究方法的新颖性开发了一个经过验证的FSI计算框架，这里专门适用于房颤患者，以从现有的抗凝药物、手术/经皮冠状动脉闭塞治疗中选择最合适的治疗策略来预防血栓栓塞事件。4)与EPSRC的策略和研究领域保持一致该项目旨在开发一个新的计算框架，以支持在为房颤患者选择最佳的血栓预防治疗时的治疗规划。这将基于无法在体内测量的流体动力学参数，并需要医学成像和计算工程的最新发展之间的协同。它与EPSRC的特定患者疾病预测、准确诊断以及改变健康和医疗保健的战略优先事项非常一致。5)任何公司或合作者参与其中巴茨NHS信托/伦敦大学学院心血管科学研究所(ICS)心血管研究联席主任皮尔·兰比亚斯教授UCLH心脏单位的奥利弗·西格尔博士和巴茨健康NHS信托博士克莱尔·马丁

1) Brief description of the context of the research including potential impactAtrial fibrillation (AF), the most prevalent cardiac arrhythmia, is characterised by rapid and disorganised heartbeats. It affects 2-3% of the population, with prevalence rising to 9% for individuals > 65 years. It is the leading cause of thromboembolic events (i.e. stroke and vascular dementia), and its projected incidence is more than double by 2035.It is estimated that > 90% of thrombi responsible for thromboembolic events under AF originate in the left atrial appendage (LAA), a complex-shaped protrusion of 2-4 cm, which departs from the left atrium (LA).The most common therapy to prevent thrombi in AF patients is oral anticoagulation; this is however contraindicated in up to 44% of AF patients, due to associated lifetime haemorrhagic risk, cost and several food/drug interactions needing frequent laboratory monitoring. Alternatively, surgical LAA exclusion can be performed applying an external suture ligation - e.g. LARIAT snare device (SentreHEART) - or a self-closing clamping device - e.g. AtriClip LAA Exclusion System (AtriCure). Percutaneous LAA occlusion devices overcome the drawbacks of invasive surgery, based on self-expanding nitinol frames supporting polyester occlusion patches. The two most common solutions are the Watchman FLX (Boston Scientific) and the Amplatzer Amulet (Abbott). However, these can develop peri-device leaks, requiring long-term anticoagulants treatment, thus inherently defeating the main procedure purpose.As all these options present major drawbacks, it is crucial to develop a novel approach to identify the patient groups for which the risk of thromboembolic events justifies a specific therapeutic approach, and the safest and most effective therapy for each subject.2) Aims and ObjectivesThe overall project goal is developing a novel computational framework to support clinical decision-making in selecting the optimal thromboembolic prevention therapy for each AF patient, identifying fluid-dynamic parameters that are impossible to measure in-vivo. 1. Analyse and segment in-vivo medical images of AF patients to obtain LAA's 3D morphological/dynamic characteristics.2. Develop Fluids Structure Interaction (FSI) computational models for the AF population, including LAA/LA anatomical features, investigating the relations between different LAA morphologies and hemodynamics, as well as the capturing of the ones not available from clinical diagnostics.3. Develop models of the main thromboembolic prevention treatments (i.e. anticoagulants and LAA excluder and occluding devices), allowing the evaluation of anatomy-treatment interaction and fluid-dynamic conditions.4. Validate the computational models with retrospective clinical data.3) Novelty of Research MethodologyDevelopment of a validated FSI computational framework, here specifically applied to AF patients, to select the most suitable therapeutic strategy to prevent thromboembolic events among those currently available: anticoagulation drugs, surgical/percutaneous occlusion of the LAA.4) Alignment to EPSRC's strategies and research areasThe project aims at developing a novel computational framework to support therapeutic-planning in the selection of the optimal thromboembolic prevention treatment for AF patients. This will be based on fluid dynamic parameters impossible to measure in-vivo, and will require the synergy between recent developments in medical imaging and computational engineering. It aligns ideally with the EPSRC's strategic priorities of patient-specific illness prediction, accurate diagnosis, and also transforming health and healthcare.5) Any companies or collaborators involvedProfessor Pier Lambiase, Co-Director of Cardiovascular Research Barts NHS Trust/UCL Institute of Cardiovascular Science (ICS)Dr Oliver Segal from Cardiac Units at UCLH and the Barts Health NHS TrustDr Claire Martin