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Abstract Timely and accurate referral of end-stage heart failure patients for advanced therapies, including heart transplants and mechanical circulatory support, plays an important role in improving patient outcomes and saving costs. However, the decision-making process is complex, nuanced, and time-consuming, requiring cardiologists with specialized expertise and training in heart failure and transplantation. In this study, we propose two logistic tensor regression-based models to predict patients with heart failure warranting evaluation for advanced heart failure therapies using irregularly spaced sequential electronic health records at the population and individual levels. The clinical features were collected at the previous visit and the predictions were made at the very beginning of the subsequent visit. Patient-wise ten-fold cross-validation experiments were performed. Standard LTR achieved an average F1 score of 0.708, AUC of 0.903, and AUPRC of 0.836. Personalized LTR obtained an F1 score of 0.670, an AUC of 0.869 and an AUPRC of 0.839. The two models not only outperformed all other machine learning models to which they were compared but also improved the performance and robustness of the other models via weight transfer. The AUPRC scores of support vector machine, random forest, and Naive Bayes are improved by 8.87%, 7.24%, and 11.38%, respectively. The two models can evaluate the importance of clinical features associated with advanced therapy referral. The five most important medical codes, including chronic kidney disease, hypotension, pulmonary heart disease, mitral regurgitation, and atherosclerotic heart disease, were reviewed and validated with literature and by heart failure cardiologists. Our proposed models effectively utilize EHRs for potential advanced therapies necessity in heart failure patients while explaining the importance of comorbidities and other clinical events. The information learned from trained model training could offer further insight into risk factors contributing to the progression of heart failure at both the population and individual levels. 

The extensive adoption of artificial intelligence in clinical decision support systems necessitates a significant presence of interpretable machine learning models. Therefore, we develop a recurrent neural network-based interpretable method, combining the fuzzy concepts and recurrent units, to train accurate and explainable models on high-dimensional longitudinal electronic health records data. Through supervised learning, our method allows the identification of variable encoding functions and significant rules. To demonstrate performance and capabilities in classification and rule discovery, we first test our method on a simulated dataset. The proposed methods achieve the best model performance compared to other methods, and the rules learned are almost identical to what we used to generate the synthetic data. Furthermore, we showcase a pilot application that proved its potential in the early detection of cardiac event onset. Our proposed algorithm obtains a comparable model performance to vanilla GRU models and remains relatively stable when the prediction window size changes. Examining the rules generated by our EvolveFNN model with the GRU unit, we find that the extracted rules not only align with clinical practices and existing literature but also provide potential risk factors not explored before in the population. The additional experiments on the MIMIC-III benchmark dataset show the algorithm's generalizability. In conclusion, our approach, EvolveFNN, can effectively train accurate, interpretable, and reliable models using large longitudinal electronic health records, thereby offering valuable insights for clinicians.