Stratification, Management, and Guidance of Hypertrophic Cardiomyopathy Patients using Hybrid Digital Twin Solutions

肥厚型心肌病（HCM）是最常见的遗传性心脏病（患病率1：200 - 1：500），表现为心壁增厚、心律失常和心源性猝死的风险增加。HCM影响所有年龄段-它是年轻运动员死亡的主要原因。由于基因突变引起的合并症包括血管控制改变，以及由HCM引起的局部缺血、中风、痴呆或心理和社会困难。多种致病突变和细胞过程的变异导致高度多样的表型和疾病进展。然而，HCM仍然被诊断为一种单一的疾病，导致次优护理。SMASH-HCM将开发一个数字孪生平台，以显著改善临床医生和患者的HCM分层和疾病管理。多层次和多器官动态生物物理和数据驱动模型集成在一个三层次的深度表型方法中，旨在快速纳入临床工作流程。SMASH-HCM联合了8家研究合作伙伴、3家医院、3家中小企业和一家全球医疗技术公司，与患者合作，推进人类数字双胞胎的最新技术水平：包括体外工具、从分子到系统水平的计算机模拟模型、结构化和非结构化数据分析、可解释的人工智能-所有这些都集成到医疗保健专业人员和患者的决策支持解决方案中。SMASH-HCM提供了对HCM的新见解，改善了患者护理和指导，验证了临床前工具，最重要的是，第一个HCM分层和管理策略，在apilot临床试验中得到验证，并与最终用户进行了测试。从而为这种复杂的疾病提供了一种具有成本效益和有效的解决方案。SMASHHCM制定了一项快速获得监管批准的战略。在实现其目标的过程中，SMASH-HCM作为未来其他心脏病数字孪生平台的基础，整合了来自各种规模和来源的模型和数据。

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease (prevalence 1:200 - 1:500), manifested by thickeningof cardiac walls, increasing risks of arrhythmia, and sudden cardiac death. HCM affects all ages - it is the leading cause of death amongyoung athletes. Comorbidities due to gene mutations include altered vascular control, and, caused by HCM, ischemia, stroke, dementia,or psychological and social difficulties. Multiple causal mutations and variations in cellular processes lead to highly diverse phenotypesand disease progression. However, HCM is still diagnosed as one single disease, leading to suboptimal care. SMASH-HCM will developa digital-twin platform to dramatically improve HCM stratification and disease management, both for clinicians and patients. Multileveland multiorgan dynamic biophysical and data-driven models are integrated in a three-level deep phenotyping approach designed forfast uptake into the clinical workflow. SMASH-HCM unites 8 research partners, 3 hospitals, 3 SMEs, and a global health-technologycorporation in collaboration with patients to advance the state of the art in human digital-twins: including in-vitro tools, in-silico frommolecular to systemic level models, structured and unstructured data analysis, explainable artificial intelligence - all integrated intoa decision support solution for both healthcare professionals and patients. SMASH-HCM delivers new insights into HCM, improvedpatient care and guidance, validated preclinical tools, and above all, a first HCM stratification and management strategy, validated in apilot clinical trial, and tested with end users. Thus providing a cost efficient and effective solution for this complex disease. SMASHHCM develops a strategy towards fast regulatory approval. In reaching its goals, SMASH-HCM serves as a basis for future digital-twinplatforms for other cardiac diseases integrating models and data from various scales and sources.