AI-Assisted Multilabel Diagnosis of 12-Lead Electrocardiograms Using an Interpretable Stacked Deep Learning Model with External Validation
Open Access
- 29 August 2026
- journal article
- research article
- Published by MDPI AG in Diagnostics
- Vol. 16 (17) , 2781
Abstract
Background: Automated interpretation of 12-lead electrocardiograms (ECGs) remains challenging because multiple abnormalities may coexist and appear in selected leads or brief waveform segments. We developed a compact and interpretable framework for five-superclass multi-label ECG diagnosis. Methods: We evaluated PTB-XL records using the official fold protocol, with folds 1–8 for training, fold 9 for validation monitoring and class-specific threshold selection, and fold 10 for independent internal testing. We then evaluated the frozen 1.33-million-parameter InceptionTime–CNN–BiGRU–Transformer model and validation-derived thresholds on 15,931 Ningbo ECGs without retraining, recalibration, or external threshold adjustment. We also examined calibration, demographic subgroups, computational efficiency, and complementary ECG-domain attribution methods. Results: Macro-AUROC reached 90.83% on PTB-XL fold 10 and 88.85% on Ningbo, indicating generally consistent diagnostic ranking with a modest reduction during external evaluation. Sensitivity analysis showed that CNN-only outperformed the frozen primary model on five of six endpoints. Attribution analyses highlighted qualitatively plausible lead and temporal patterns in representative examples, while calibration and subgroup analyses further characterized model behavior under dataset shift. Conclusions: Our framework integrates leakage-aware development, threshold-controlled testing, frozen external validation, and multimethod interpretability. These findings support its further prospective, locally calibrated evaluation as a potential aid for multi-label ECG interpretation.Keywords
This publication has 36 references indexed in Scilit:
- Interpretable deep learning framework for multi-label ECG classification: Enhancing cardiac diagnostics through feature attention and explainabilityBiomedical Signal Processing and Control, 2025
- Show and tell: A critical review on robustness and uncertainty for a more responsible medical AIInternational Journal of Medical Informatics, 2025
- Empirical investigation of multi-source cross-validation in clinical ECG classificationComputers in Biology and Medicine, 2024
- Leadwise clustering multi-branch network for multi-label ECG classificationMedical Engineering & Physics, 2024
- The need to separate the wheat from the chaff in medical informaticsInternational Journal of Medical Informatics, 2021
- InceptionTime: Finding AlexNet for time series classificationData Mining and Knowledge Discovery, 2020
- Automatic diagnosis of the 12-lead ECG using a deep neural networkNature Communications, 2020
- Deep learning for time series classification: a reviewData Mining and Knowledge Discovery, 2019
- Screening for cardiac contractile dysfunction using an artificial intelligence–enabled electrocardiogramNature Medicine, 2019
- AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the ElectrocardiogramJACC, 2009