Body surface potential driven personalisation of electrophysiological digital twins in hypertrophic cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated with marked inter-patient heterogeneity in ventricular electrophysiology, contributing to arrhythmic risk that is insufficiently captured by current clinical methods. Electrocardiographic imaging (ECGI) provides high-density body surface potential (BSP) measurements but remains largely descriptive. Computational modelling offers a mechanistic framework to interpret BSP signals in terms of underlying tissue-level properties. METHODS AND FINDINGS: We developed a BSP-driven workflow to construct patient-specific electrophysiology (EP) models of HCM by integrating multimodal clinical imaging with Bayesian model calibration. Anatomically detailed torso-heart finite-element models were generated for 17 HCM patients using thoracic computed tomography (CT), cardiac magnetic resonance imaging (CMR), and 252-electrode BSP recordings. Ventricular depolarisation and repolarisation were simulated using a reaction-eikonal (RE) formulation coupled to a biophysically detailed ToR-ORd-dynCl ionic model. Emulator-based Bayesian history matching (HM) was used to personalise EP parameters, with staged calibration of QRS and T-wave morphology informed by targeted sensitivity analysis. The calibrated cohort reproduced clinical BSP morphology with Pearson correlation coefficient (PCC) [Formula: see text] for a median of 94.0% (IQR: 91.6 to 96.8%) of electrodes, achieving a median PCC of 0.89 (IQR: 0.80 to 0.94) across the full 252-electrode vest. Calibration substantially reduced uncertainty in the high-dimensional EP parameter space while yielding physiologically plausible conduction and repolarisation properties. Models calibrated exclusively to sinus rhythm robustly generalised to right-ventricular (RV) apical pacing without parameter retuning, reproducing clinically observed pacing-induced trends in depolarisation and repolarisation. Exploratory analysis revealed biologically consistent associations between inferred EP parameters and patient demographics. CONCLUSIONS: This study demonstrates that high-density BSP data can be used to functionally personalise mechanistic EP in HCM. The framework captures intrinsic patient-specific EP properties and generalises beyond the calibration condition, supporting its use for mechanistic investigation of arrhythmogenic substrate.