Developing Cardiac Digital Twins at Scale: Insights from Personalised Myocardial Conduction Velocity.

Large-cohort studies using cardiovascular imaging and diagnostic datasets have assessed cardiac anatomy, function, and outcomes, but typically do not reveal underlying biological mechanisms. Cardiac digital twins (CDTs) provide personalized physics- and physiology-constrained in-silico representations, enabling inference of multi-scale properties tied to these mechanisms. We constructed 3464 anatomically-accurate CDTs using cardiac magnetic resonance images from UK biobank and personalised their myocardial conduction velocities (CVs) from electrocardiograms (ECG), through an automated framework. We found well-known sex-specific differences in QRS duration were fully explained by myocardial anatomy, as CV remained consistent across sexes. Conversely, significant associations of CV with ageing and increased BMI suggest myocardial tissue remodelling. Novel associations were observed with left ventricular ejection fraction and mental-health phenotypes, through a phenome-wide association study, and CV was also linked with adverse clinical outcomes. Our study highlights the utility of population-based CDTs in assessing intersubject variability and uncovering strong links with mental health.