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

1)简要描述研究背景，包括潜在影响房颤（AF）是最常见的心律失常，其特征是快速和无组织的心跳。它影响人口的2-3%，在65岁以上的人群中患病率上升到9%。它是血栓栓塞事件（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，90%导致房颤的血栓栓塞事件的血栓起源于左房附件（LAA），这是一个2-4厘米的复杂形状的突出物，离开左心房（LA）。预防房颤患者血栓最常用的治疗方法是口服抗凝；然而，由于相关的终身出血风险、成本和需要频繁实验室监测的几种食物/药物相互作用，高达44%的房颤患者忌用这种方法。另外，可以应用外部缝合结扎（例如LARIAT圈套装置（SentreHEART））或自闭合夹紧装置（例如AtriClip LAA排除系统（AtriCure））进行手术LAA排除。经皮LAA闭塞装置克服了侵入性手术的缺点，基于自膨胀镍钛诺框架支持聚酯闭塞贴片。两种最常见的解决方案是Watchman FLX（波士顿科学）和Amplatzer护身符（雅培）。然而，这些可能会导致装置周围泄漏，需要长期的抗凝治疗，因此本质上违背了主要的手术目的。由于所有这些选择都存在主要的缺点，因此开发一种新的方法来确定具有血栓栓塞事件风险的特定治疗方法的患者群体，以及对每个受试者最安全和最有效的治疗方法至关重要。2)目的和目标总体项目目标是开发一个新的计算框架，以支持临床决策，为每位房颤患者选择最佳的血栓栓塞预防治疗，识别体内无法测量的流体动力学参数。1. 1 .对AF患者体内医学图像进行分析和分割，获得LAA的三维形态/动态特征。2 .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。3 .建立主要血栓栓塞预防治疗（即抗凝剂和LAA排除剂和闭塞装置）的模型，允许评估解剖-治疗相互作用和流体动力学条件。用回顾性临床数据验证计算模型。3)研究方法的新颖性：开发一个经过验证的FSI计算框架，专门应用于房颤患者，以选择最合适的治疗策略，以防止目前可用的血栓栓塞事件：与EPSRC的策略和研究领域保持一致该项目旨在开发一种新的计算框架，以支持AF患者选择最佳血栓栓塞预防治疗的治疗计划。这将基于不可能在体内测量的流体动力学参数，并且将需要医学成像和计算工程的最新发展之间的协同作用。它与EPSRC的战略重点——针对特定患者的疾病预测、准确诊断，以及改变健康和医疗保健——完美契合。5)任何涉及的公司或合作者，包括心血管研究联合主任，Barts NHS信托/UCL心血管科学研究所（ICS）， UCLH心脏科的Oliver Segal博士和Barts Health NHS Trust的Claire Martin博士

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