Cardiovascular Digital Twins from Physics Based to Data Driven Approaches

A digital twin (DT) of a patient-specific heart offers significant potential in personalized medicine. However, its rapid and dynamic adaptation to an individual's live data and its predictive capability after adaptation remains central challenges. We examine this challenge from its two building blocks: DT formulation where mechanistic and data-driven models show competing merits and limitations, and DT optimization strategies that are largely driven by a reconstruction objective leading to un-identifiable models. We address both bottlenecks via HAPI -- an AI framework for building hybrid, adaptive, and predictive DTs with three key enablers. First, HAPI constructs a physics-integrated gray-box model in which an interpretable mechanistic backbone is augmented by a neural component that models its residual to the observed data. Second, rather than attempting to pre-encode all possible variations in a static hybrid model, HAPI enables rapid on-the-fly adaptation of the hybrid model to few-shot live data, achieved by feedforward meta-learners realizing amortized inference of both mechanistic and neural parameters of the hybrid model trained with predictive objectives. Finally, we show that this adaptivity corresponds to the construction of a conditional generative model (i.e., the hybrid DT) that endows it with theoretical identifiability and thus strong performance in predictive scenarios. We demonstrate the proof-of-concept of HAPI in cardiac electrophysiology using a hybrid monodomain model with mechanistic reaction kinetics and neural graph diffusion. Across synthetic and real-data studies, we show that HAPI's mechanistic-neural hybridization and predictive adaptation are critical for obtaining identifiable DTs with strong predictive and out-of-distribution capabilities.

Clinical decision-making for coronary intervention relies mainly on angiography and fractional flow reserve (FFR). However, angiography is two-dimensional and lacks depth information for 3D lesion characterization, while FFR provides only a single functional index, offering limited hemodynamic insight. Among existing methods, numerical analysis is computationally expensive, whereas learning-based approaches require extensive supervision and often lack physical consistency. To address these limitations, we propose physics-informed hemodynamic modeling, an integrated deep learning framework for 3D coronary blood flow analysis from dual-view angiography. First, an attention-enhanced CNN reconstructs coronary geometry from angiography. The resulting point clouds are then mapped to a reference domain and Fourier-encoded for joint representation. A decoupled network separately predicts velocity and pressure fields, with embedded physical priors enabling efficient transfer across physiological conditions. Across 32 clinical patients evaluated under four flow conditions, the trans-stenotic pressure-drop mean absolute percentage error was 2.02%, while the velocity and pressure relative-L2 errors were 0.054 and 0.023, respectively. Validation against hospital-measured FFR further achieved 93.8% diagnostic accuracy (30/32; exact 95% CI, 79.2%-99.2%). The framework also supports illustrative revascularization comparisons and sparse-data assimilation, with the full angiography-to-hemodynamics pipeline completed within 20 minutes per patient.

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