Predicting one-year clinical instability and mortality in heart failure patients using sequence modeling

Heart failure (HF) discharge planning depends on identifying patients at risk of deterioration or death, yet accurate prediction from routinely collected electronic health records (EHRs) remains challenging. We developed and validated sequence models for three one-year prediction tasks in a Swedish HF cohort (N = 42,820): clinical instability (a rehospitalization phenotype) and mortality after the initial in-hospital HF diagnosis, and mortality after the latest hospitalization. A modular three-component framework transforms structured EHRs into patient sequences by specifying tokenization strategies, temporal representations, and model configurations. Patient data included diagnoses, vital signs, laboratories, medications, and procedures. Autoregressive next-token prediction models consistently outperformed alternative objectives in short-context settings (<= 512 tokens). The best model (Llama) achieved AUPRCs (95% CI) of 0.555 (0.535-0.575), 0.582 (0.558-0.608), and 0.854 (0.842-0.865), with robust calibration. Ablations show Llama and Mamba variants learn efficient patient representations, with tiny configurations surpassing larger conventional baselines, indicating that model size alone does not improve performance. With limited clinical concepts or training data, Llama maintains strong performance, frequently surpassing full-data baselines. Combining clinical instability and mortality predictions defines four distinct care pathways, from standard primary care to intensive home care, supporting patient-centered decisions at discharge. These findings demonstrate accurate risk prediction from routine hospital data, provide actionable development guidance, and support post-discharge risk stratification.