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(患病率为1：200-1：500)，表现为心壁增厚、心律失常和心脏性猝死。HCM影响各个年龄段--它是年轻运动员死亡的主要原因。基因突变引起的共病包括血管控制改变，以及由肥厚性心肌炎引起的缺血、中风、痴呆或心理和社会困难。细胞过程中的多种原因突变和变异导致高度不同的表型和疾病进展。然而，肥厚型心肌炎仍然被诊断为一种单一疾病，导致了不理想的治疗。SMASH-HCM将开发一个数字孪生平台，为临床医生和患者显著改善HCM分层和疾病管理。多层次、多器官、动态、生物物理和数据驱动的模型被集成在一个三个层次的深度表型方法中，旨在快速融入临床工作流程。SMASH-HCM联合了8个研究伙伴、3家医院、3家中小企业和一家全球健康技术公司，与患者合作，推动人类数字双胞胎的最先进水平：包括体外工具、从分子到系统级别的硅胶模型、结构化和非结构化数据分析、可解释人工智能-所有这些都集成到为医疗保健专业人员和患者提供的决策支持解决方案中。SMASH-HCM提供了对HCM的新见解，改进了患者护理和指导，验证了临床前工具，最重要的是，提供了第一个HCM分层和管理策略，在Ailot临床试验中进行了验证，并在最终用户中进行了测试。从而为这种复杂的疾病提供了一种经济有效的解决方案。SMASHHCM制定了一项旨在快速获得监管批准的战略。为了实现其目标，SMASH-HCM成为未来其他心脏病的数字孪生平台的基础，该平台集成了来自不同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.