Detecting Structural Heart Disease from Electrocardiograms via a Generalized Additive Model of Interpretable Foundation-Model Predictors

Transthoracic echocardiography is the reference standard for confirming structural heart disease (SHD), but first-line screening is limited by cost, workflow burden, and specialist availability. We evaluated whether open pretrained electrocardiogram (ECG) foundation models can support echo-confirmed multi-label SHD detection using the public EchoNext Mini-Model benchmark. Six echocardiography-derived abnormalities were targeted: reduced left ventricular ejection fraction, increased left ventricular wall thickness, aortic stenosis, mitral regurgitation, tricuspid regurgitation, and right ventricular systolic dysfunction. Under a common pipeline, we compared engineered ECG features with gradient boosting, end-to-end waveform learning from scratch, and transfer from open ECG foundation models. We then applied in-domain self-supervised adaptation of an ECG foundation model (ECG-FM) on EchoNext waveforms followed by selective supervised fine-tuning, and evaluated trade-offs between discrimination and adaptation cost. Adapted ECG-FM models achieved the best overall performance: peak macro-AUROC 0.8509 and macro-AUPRC 0.4297, while a parameter-efficient operating point preserved AUROC (0.8501) and attained the highest fixed-threshold macro-F1 0.3691. Late fusion with covariates did not improve threshold-independent discrimination, and evaluated LoRA, alternative backbones, and mixture-of-foundations strategies did not surpass the best adapted single-backbone models. These results indicate that for ECG-based case finding and echocardiography triage, combining target-domain self-supervised adaptation with selective supervised updating of a pretrained ECG backbone is the most effective transfer strategy.

Low left ventricular ejection fraction (LEF) frequently remains undetected until progression to symptomatic heart failure, underscoring the need for scalable screening strategies. Although artificial intelligence-enabled electrocardiography (AI-ECG) has shown promise, existing approaches rely solely on end-to-end black-box models with limited interpretability or on tabular systems dependent on commercial ECG measurement algorithms with suboptimal performance. We introduced ECG-based Predictor-Driven LEF (ECGPD-LEF), a structured framework that integrates foundation model-derived diagnostic probabilities with interpretable modeling for detecting LEF from ECG. Trained on the benchmark EchoNext dataset comprising 72,475 ECG-echocardiogram pairs and evaluated in predefined independent internal (n=5,442) and external (n=16,017) cohorts, our framework achieved robust discrimination for moderate LEF (internal AUROC 88.4%, F1 64.5%; external AUROC 86.8%, F1 53.6%), consistently outperforming the official end-to-end baseline provided with the benchmark across demographic and clinical subgroups. Interpretability analyses identified high-impact predictors, including normal ECG, incomplete left bundle branch block, and subendocardial injury in anterolateral leads, driving LEF risk estimation. Notably, these predictors independently enabled zero-shot-like inference without task-specific retraining (internal AUROC 75.3-81.0%; external AUROC 71.6-78.6%), indicating that ventricular dysfunction is intrinsically encoded within structured diagnostic probability representations. This framework reconciles predictive performance with mechanistic transparency, supporting scalable enhancement through additional predictors and seamless integration with existing AI-ECG systems.

Electrocardiography (ECG) is a cornerstone of cardiac diagnosis, yet most machine learning methods for ECG analysis lack interpretability, limiting their clinical adoption. We present IECG, a weakly-supervised ECG foundation model that jointly performs diagnostic classification and abnormality localization without requiring manual abnormal region annotations, overcoming a long-standing bottleneck in interpretable ECG learning. Central to IECG is a weakly-supervised attention strategy that explicitly incorporates clinical priors by deriving abnormality heatmap pseudo-labels from established ECG clinical knowledge. These pseudo-labels guide the model's CLS-token attention through a KL-divergence loss, encouraging it to focus on diagnostically relevant waveform regions. During pretraining, IECG is jointly optimized with clinically guided attention supervision, ECG-text contrastive alignment, and report captioning objectives, enabling it to learn rich multimodal representations while producing localized waveform evidence. By explicitly aggregating features from clinically guided attention regions, IECG grounds its diagnostic predictions in interpretable waveform evidence without sacrificing classification performance. Extensive experiments demonstrate that IECG achieves state-of-the-art abnormal region localization while maintaining strong classification performance, advancing trustworthy foundation models for ECG analysis.