When Measurement Conventions Masquerade as Calibration Gains in Cardiac Digital Twins
Authors: Dang P. M. Cao, Hieu Pham
Organizations: College of Engineering and Computer Science, VinUniversity, Hanoi, Vietnam · VinUni-Illinois Smart Health Center, VinUniversity, Hanoi, Vietnam · Center for Innovations in Health Sciences, VinUniversity, Hanoi, Vietnam
Abstract
Cardiac digital twins convert clinical images into physiological measurements through observation operators, yet calibration studies often assume a fixed reference convention. Across four shared-backbone echocardiographic EF front-ends, phase conditioning appears to remove CAMUS baseline bias. Matched-reference analysis rejects this gain: singleplane ground-truth EF error is statistically indistinguishable across models, while single-plane ground-truth EF exceeds CAMUS biplane clinical EF by +6.30 points, explaining nearly all baseline bias. A prespecified EchoNet-Dynamic replication, with released data and our extractor aligned to the apical four-chamber plane, removes baseline overestimation and reverses the CAMUS ranking. We also quantify haemodynamic effects, conformal residual-width budgets, and EF-stratum changes, yielding a Convention-Aware EF Audit protocol that separates genuine observation operator calibration from measurement artefacts. GitHub: EjectionFraction-Bias-in-Cardiac-Digital-Twin.git
Cardiovascular digital twins aim to create patient-specific computational models that evolve with clinical data to support diagnosis, prognosis, and therapy optimisation. Mechanistic models provide physiological interpretability but remain computationally demanding, whereas data-driven approaches improve scalability yet risk limited robustness. Emerging physics-informed, graph-based, and hybrid methods integrate physical constraints with relational learning across vascular networks. We review modelling paradigms, data assimilation frameworks, validation challenges, and translational pathways toward clinically deployable cardiovascular digital twins.
Left ventricular ejection fraction (LVEF) is a primary marker of cardiac function. However, routine estimation from endocardial measurements requires manual delineation at end-diastole (ED) and end-systole (ES), a process that is time-consuming and subject to inter-observer variability. Reliable automation is especially valuable for point-of-care ultrasound (POCUS), where computational resources are limited and acquisition quality varies. We propose Echo-E3Net, an anatomy-guided spatio-temporal network that explicitly embeds cardiac anatomy into LVEF prediction. A dual-phase Endocardial Border Detector (E2CBD) uses phase-specific cross-attention to localize ED/ES endocardial landmarks and produce phase-aware landmark embeddings, while an Endocardial Feature Aggregator (E2FA) fuses these embeddings with global statistical descriptors of deep feature maps to refine EF regression. Training is guided by a lightweight geometric loss that uses ED and ES endocardial landmarks to regularize EF prediction. On EchoNet-Dynamic and a PSAX subset of EchoNet-Pediatric, Echo-E3Net attains competitive performance using only 1.55M parameters and 8.05 GFLOPs, an order-of-magnitude compute reduction versus recent baselines, supporting real-time deployment. Our code is publicly available at https://github.com/moeinheidari7829/Echo-E3Net.
Accurate localization of myocardial infarction is essential for risk stratification. While LGE-MRI remains the gold standard, it is resource-intensive. Integrating cine MRI with ECG enables a more detailed representation of infarct properties. Existing inverse MI inference methods overlook realistic scar morphology and cardiac repolarization, reducing sensitivity to subtle ECG variations and interpretability of infarct-induced electrophysiological changes. In this paper, we propose a novel framework for noninvasive MI localization using cardiac digital twins. To bridge the domain gap between simulation and reality, we introduce an anatomy-aware stochastic infarct synthesis strategy to synthesize realistic, irregular scars with border zones, mimicking ischemic transmural progression. We then construct a virtual cohort to simulate QRS-T waveforms, capturing both depolarization and repolarization dynamics. Furthermore, we design a Physiology and Anatomy Aware Network (PAA-Net) that jointly encodes 3D myocardial geometry and multi-lead ECGs to infer infarct areas with varying localizations, sizes, spatial extents, and transmuralities. Experimental results demonstrate that our framework significantly outperforms existing methods in inverse inference, achieving Dice scores of 0.7391 and 0.5503 for scar and border zone segmentation, respectively, while further enhancing the interpretability of the ECG-infarct relationship. Our code will be released upon acceptance.