Leveraging Cardiac Imaging to Improve ECG-Based Detection of Chagas Disease in Resource-Constrained Settings

Cardiac Magnetic Resonance (CMR) imaging provides a comprehensive assessment of cardiac structure and function but remains constrained by high acquisition costs and reliance on expert annotations, limiting the availability of large-scale labeled datasets. In contrast, electrocardiograms (ECGs) are inexpensive, widely accessible, and offer a promising modality for conditioning the generative synthesis of cine CMR. To this end, we propose ECGFlowCMR, a novel ECG-to-CMR generative framework that integrates a Phase-Aware Masked Autoencoder (PA-MAE) and an Anatomy-Motion Disentangled Flow (AMDF) to address two fundamental challenges: (1) the cross-modal temporal mismatch between multi-beat ECG recordings and single-cycle CMR sequences, and (2) the anatomical observability gap due to the limited structural information inherent in ECGs. Extensive experiments on the UK Biobank and a proprietary clinical dataset demonstrate that ECGFlowCMR can generate realistic cine CMR sequences from ECG inputs, enabling scalable pretraining and improving performance on downstream cardiac disease classification and phenotype prediction tasks.

Electrocardiography (ECG) is central to cardiovascular care, but conventional AI models are often restricted to common arrhythmias and may generalize poorly across populations or clinically subtle diseases. We developed ECG Contrastive Language-Image Pre-training (ECGCLIP), a signal-language contrastive learning framework that aligns ECG waveforms with expert diagnostic reports. ECGCLIP was pre-trained on 2,837,962 ECG studies from 1,324,856 patients and evaluated on a held-out internal test set plus nine independent external cohorts comprising about 1.5 million ECGs. Evaluation covered 89 downstream tasks, including 45 ECG diagnoses, 39 echocardiographic targets, and 5 rare cardiac diseases, using PRAUC as the primary metric. ECGCLIP consistently improved performance over random initialization and Merl-R18 baselines. On the internal test set, ECGCLIP-R34 achieved strong performance for atrial fibrillation (PRAUC 0.900) and ST-segment elevation myocardial infarction (PRAUC 0.383), with robust generalization across all external cohorts. It also improved low-prevalence and diagnostically elusive diseases, including Ebstein anomaly, constrictive pericarditis, dextrocardia, and cardiac amyloidosis, with internal PRAUC values of 0.253, 0.175, 0.121, and 0.201, respectively. ECGCLIP was data efficient, matching or exceeding full-dataset baseline performance with only 10% of training data. Feature visualization and saliency analysis suggested clinically meaningful representations aligned with established electrocardiographic criteria. These findings indicate that large-scale ECG-report contrastive pre-training can expand routine ECG interpretation beyond common arrhythmias toward broad cardiovascular assessment and opportunistic screening of echocardiographic and rare conditions.

Background: Foundation models (FMs) trained on large-scale unlabeled physiological data have emerged as a promising paradigm for medical artificial intelligence. Their ability to capture clinically meaningful, transferable representations for rare diseases remains largely unproven. This study investigates whether FM pre-training provides genuine clinical generalization benefits beyond improved optimization for rare electrocardiographic (ECG) phenotypes. Methods: We systematically evaluated nine publicly available ECG FMs for Brugada syndrome detection on the BrSwiss cohort (294 patients, 87 cases) and the independent external HUCA cohort (363 patients, 76 cases), under three strategies (from-scratch training, linear probing, full fine-tuning) across several configurations, including a 3% data ablation and zero-shot cross-site transfers. Results: Pre-training was necessary for high-capacity architectures unable to converge from scratch (AUC gain up to 0.411, p < 0.05), but gave no significant gain for compact architectures already converged on labeled data alone. On full BrSwiss, the best fine-tuned FM (ECG-CPC, AUC = 0.962) only marginally exceeded the strongest supervised baseline (ECG-CPC from scratch, AUC = 0.932; p = 0.091). At matched training-set size, the data-efficiency advantage on BrSwiss-3% (AUC gain = 0.055, p < 0.01) did not replicate on HUCA. Under zero-shot cross-site transfer, FM-based pipelines did not generalize better than supervised baselines, all approaching chance-level performance. Conclusion: For Brugada syndrome detection, FM pre-training is mechanical rather than semantic, providing optimization stability rather than transferable clinical knowledge. These findings challenge the assumption that large-scale pre-training inherently encodes clinically meaningful representations, highlighting the central role of model architecture and data-domain alignment.