Building personalized cardiac electrophysiology (EP) digital twins requires identifying the appropriate model structure for each patient, not merely fitting parameters. Traditional methods rely on experts to manually prescribe hybrid physics-neural architectures, which requires deep domain expertise and does not transfer across patients. Recent works have applied large language models (LLMs) to generate or act as hybrid models. However, despite their promising generalization capacity, these LLM-based methods lack the structural priors needed for stable cardiac simulations. Hence, we propose LEADS, a framework that formulates cardiac EP domain knowledge as a structured action space and utilizes an LLM agent to discover hybrid models. The agent follows an iterative reasoning-and-action loop to select, combine, and refine hybrid models, whilst gradient descent handles parameter fitting. The proposed LEADS designs every candidate model towards physically grounded, interpretable, and numerically stable, while allowing open-ended architectural discovery. We validate LEADS on synthetic data with three ground-truth reaction models and on real cardiac EP data, demonstrating that it outperforms both human-designed hybrid models and other LLM-based hybrid modeling.
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.
ECG-Language Models (ELMs) extend recent advances in Multimodal Large Language Models (MLLMs) to automated ECG interpretation. However, most existing ELMs inherit Vision-Language Model (VLM) design choices and rely on pretrained ECG encoders, introducing substantial architectural and training complexity. Inspired by encoder-free VLMs, we introduce ELF, a family of three encoder-free ELMs that remain competitive with, and often outperform, prior state-of-the-art ELMs across two datasets despite substantially simpler architectures and training pipelines. All code and data are available at github.com/ELM-Research/ECG-Language-Models.
Self-supervised learning in healthcare has largely relied on invariance-based objectives, which maximize similarity between different views of the same patient. While effective for static anatomy, this paradigm is fundamentally misaligned with clinical diagnosis, as it mathematically compels the model to suppress the transient pathological changes it is intended to detect. We propose a shift towards Action-Conditioned World Models that learn to simulate the dynamics of disease progression, or Event-Conditioned. Adapting the LeJEPA framework to physiological time-series, we define pathology not as a static label, but as a transition vector acting on a patient's latent state. By predicting the future electrophysiological state of the heart given a disease onset, our model explicitly disentangles stable anatomical features from dynamic pathological forces. Evaluated on the MIMIC-IV-ECG dataset, our approach outperforms fully supervised baselines on the critical triage task. Crucially, we demonstrate superior sample efficiency: in low-resource regimes, our world model outperforms supervised learning by over 0.05 AUROC. These results suggest that modeling biological dynamics provides a dense supervision signal that is far more robust than static classification. Source code is available at https://github.com/cljosegfer/lesaude-dynamics
Jose Geraldo Fernandes, Luiz Facury, Pedro Robles Dutenhefner +1