Qian Shuang, Ugurlu Devran, Fairweather Elliot, Toso Laura Dal, Deng Yu, Strocchi Marina, Cicci Ludovica, Jones Richard E, Zaidi Hassan, Prasad Sanjay, Halliday Brian P, Hammersley Daniel, Liu Xingchi, Plank Gernot, Vigmond Edward, Razavi Reza, Young Alistair, Lamata Pablo, Bishop Martin, Niederer Steven
National Heart and Lung Institute, Imperial College London, London, UK.
Department of Biomedical Engineering, School of Imaging Sciences and Biomedical Engineering, King's College London, London, UK.
Nat Cardiovasc Res. 2025 May;4(5):624-636. doi: 10.1038/s44161-025-00650-0. Epub 2025 May 16.
Large-cohort imaging and diagnostic studies often assess cardiac function but overlook underlying biological mechanisms. Cardiac digital twins (CDTs) are personalized physics-constrained and physiology-constrained in silico representations, uncovering multi-scale insights tied to these mechanisms. In this study, we constructed 3,461 CDTs from the UK Biobank and another 359 from an ischemic heart disease (IHD) cohort, using cardiac magnetic resonance images and electrocardiograms. We show here that sex-specific differences in QRS duration were fully explained by myocardial anatomy while their myocardial conduction velocity (CV) remains similar across sexes but changes with age and obesity, indicating myocardial tissue remodeling. Longer QTc intervals in obese females were attributed to larger delayed rectifier potassium conductance . These findings were validated in the IHD cohort. Moreover, CV and were associated with cardiac function, lifestyle and mental health phenotypes, and CV was also linked with adverse clinical outcomes. Our study demonstrates how CDT development at scale reveals biological insights across populations.
大型队列成像和诊断研究通常会评估心脏功能，但却忽略了潜在的生物学机制。心脏数字孪生（CDT）是个性化的、受物理和生理约束的计算机模拟模型，能够揭示与这些机制相关的多尺度见解。在本研究中，我们利用心脏磁共振图像和心电图，从英国生物银行构建了3461个CDT，并从缺血性心脏病（IHD）队列中构建了另外359个。我们在此表明，QRS波时限的性别特异性差异完全由心肌解剖结构所解释，而其心肌传导速度（CV）在性别之间保持相似，但会随着年龄和肥胖而变化，这表明存在心肌组织重塑。肥胖女性较长的QTc间期归因于更大的延迟整流钾电导。这些发现在IHD队列中得到了验证。此外，CV和与心脏功能、生活方式和心理健康表型相关，并且CV还与不良临床结局有关。我们的研究展示了大规模CDT开发如何揭示不同人群的生物学见解。
