Uncertainty estimation for deep learning-based automated analysis of 12-lead electrocardiograms

Automated interpretation of electrocardiograms (ECGs) using deep neural networks (DNNs) has gained much attention recently. While the initial results have been encouraging, limited attention has been paid to whether such results can be trusted, which is paramount for their clinical implementation. This study aims to systematically investigate uncertainty estimation techniques for automated classification of ECGs using DNNs and to gain insight into its utility through a clinical simulation. On a total of 526 656 ECGs from three different datasets, six different methods for estimation of aleatoric and epistemic uncertainty were systematically investigated. The methods were evaluated based on ranking, calibration, and robustness against out-of-distribution data. Furthermore, a clinical simulation was performed where increasing uncertainty thresholds were applied to achieve a clinically acceptable performance. Finally, the correspondence between the uncertainty of ECGs and the lack of interpretational agreement between cardiologists was estimated. Results demonstrated the largest benefit when modelling both epistemic and aleatoric uncertainty. Notably, the combination of variational inference with Bayesian decomposition and ensemble with auxiliary output outperformed the other methods. The clinical simulation showed that the accuracy of the algorithm increased as uncertain predictions were referred to the physician. Moreover, high uncertainty in DNN-based ECG classification strongly corresponded with a lower diagnostic agreement in cardiologist's interpretation (