Fiche publication
Date publication
novembre 2022
Journal
IEEE transactions on bio-medical engineering
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FELBLINGER Jacques
Tous les auteurs :
Diaw MD, Papelier S, Durand-Salmon A, Felblinger J, Oster J
Lien Pubmed
Résumé
Rate-corrected QT interval (QTc) prolongation has been suggested as a biomarker for the risk of drug-induced torsades de pointes, and is therefore monitored during clinical trials for the assessment of drug safety. Manual QT measurements by expert ECG analysts are expensive, laborious and prone to errors. Wavelet-based delineators and other automatic methods do not generalize well to different T wave morphologies and may require laborious tuning. Our study investigates the robustness of convolutional neural networks (CNNs) for QT measurement. We trained 3 CNN-based deep learning models on a private ECG database with human expert-annotated QT intervals. Among these models, we propose a U-Net model, which is widely used for segmentation tasks, to build a novel clinically useful QT estimator that includes QT delineation for better interpretability. We tested the 3 models on four external databases, amongst which a clinical trial investigating four drugs. Our results show that the deep learning models are in stronger agreement with the experts than the state-of-the-art wavelet-based algorithm. Indeed, the deep learning models yielded up to 71% of accurate QT measurements (absolute difference between manual and automatic QT below 15 ms) whereas the wavelet-based algorithm only allowed 52% of QT accuracy. For the 2 studies of drugs with small to no QT prolonging effect, a mean absolute difference of 6 ms (std = 5 ms) was obtained between the manual and deep learning methods. For the other 2 drugs with more significant effect on the volunteers, a mean difference of up to 17 ms (std = 17 ms) was obtained. The proposed models are therefore promising for automated QT measurements during clinical trials. They can analyze various ECG morphologies from a diversity of individuals although some QT-prolonged ECGs can be challenging. The U-Net model is particularly interesting for our application as it facilitates expert review of automatic QT intervals, which is still required by regulatory bodies, by providing QRS onset and T offset positions that are consistent with the estimated QT intervals.
Référence
IEEE Trans Biomed Eng. 2022 11 10;PP:
