A Heterogeneous Graph Neural Network Framework for Multi-Horizon Stroke Mortality Prediction

Background: Machine learning models for stroke mortality prediction typically treat each time horizon independently and use flat tabular features that ignore the relational structure of electronic health records (EHRs). In this pilot study, we leveraged graph-based machine learning models to predict post stroke all-cause-mortality across three different time horizons. Methods: We developed Stroke Temporal Heterogeneous Graph (StrokeTHG), a heterogeneous graph neural network model for simultaneous multi-horizon stroke mortality prediction (30-day, 90-day, 1-year) using EHR data from Penn State Health System. The model encodes various relations among EHR entities (e.g., patient, diagnosis, comorbidity) and temporal encoding of admission time to better predict stroke mortality. We compared our proposed approach against various baseline methods, including Logistic Regression, Random Forest, and XGBoost. We also performed ablation and subgroup analyses, evaluated the quality of learned graph embeddings, and assessed the importance of different edge types in the graph. Results: We included 4,144 stroke patients (mean age 69.2 years; 54.3% men), of whom 3,332 (80.4%) survived their stroke after one year. 30-day, 90-day, and 1-year mortality rates were 9.7%, 13.7%, and 19.6%, respectively. Our proposed approach, StrokeTHG, achieved AUROC of 0.872, 0.878, and 0.837 across horizons, outperforming all tabular baselines. At [≥] , 75% specificity, the model identified 5-10 percentage points more mortality cases than the best baseline at each horizon. Subgroup analysis demonstrated consistent performance across sex subgroups and the largest discriminative gains in the Age 65-80 stratum. Edge-type ablation identified phenotype-patient and admission-patient edges in the constructed EHR graph as the most influential relational edges for mortality prediction. StrokeTHG embeddings outperformed all graph and matrix factorization baselines under an identical downstream classifier, confirming that performance gains stem from representation quality rather than classifier capacity. Conclusions: StrokeTHG demonstrates that heterogeneous graph representations of EHR data provide a consistent improvement over flat tabular models for multi-horizon stroke mortality prediction, with particular advantage at clinically actionable sensitivity thresholds and novel multi-horizon monotonic prediction capability. This methodological framework may be adaptable to other EHR-based clinical research studies seeking to leverage heterogeneous relational structures for predictive modeling.