Tracing the Heart: An Evidence-Linked Pipeline for Heart-Failure Feature Engineering

Feature engineering for Electronic Health Records (EHR) is complicated by irregular observation intervals, variable measurement frequencies, and structural sparsity inherent to clinical time series. Existing automated methods either lack clinical domain awareness or assume clean, regularly sampled inputs, limiting their applicability to real-world EHR data. We present \textbf{FeatEHR-LLM}, a framework that leverages Large Language Models (LLMs) to generate clinically meaningful tabular features from irregularly sampled EHR time series. To limit patient privacy exposure, the LLM operates exclusively on dataset schemas and task descriptions rather than raw patient records. A tool-augmented generation mechanism equips the LLM with specialized routines for querying irregular temporal data, enabling it to produce executable feature-extraction code that explicitly handles uneven observation patterns and informative sparsity. FeatEHR-LLM supports both univariate and multivariate feature generation through an iterative, validation-in-the-loop pipeline. Evaluated on eight clinical prediction tasks across four ICU datasets, our framework achieves the highest mean AUROC on 7 out of 8 tasks, with improvements of up to 6 percentage points over strong baselines. Code is available at github.com/hojjatkarami/FeatEHR-LLM.

Cancer treatments are known to introduce cardiotoxicity, negatively impacting outcomes and survivorship. Identifying cancer patients at risk of heart failure (HF) is critical to improving cancer treatment outcomes and safety. This study examined machine learning (ML) models to identify cancer patients at risk of HF using electronic health records (EHRs), including traditional ML, Time-Aware long short-term memory (T-LSTM), and large language models (LLMs) using novel narrative features derived from the structured medical codes. We identified a cancer cohort of 12,806 patients from the University of Florida Health, diagnosed with lung, breast, and colorectal cancers, among which 1,602 individuals developed HF after cancer. The LLM, GatorTron-3.9B, achieved the best F1 scores, outperforming the traditional support vector machines by 39%, the T-LSTM deep learning model by 7%, and a widely used transformer model, BERT, by 5.6%. The analysis shows that the proposed narrative features remarkably increased feature density and improved performance.

Artificial intelligence-enabled electrocardiography (AI-ECG) can detect heart failure (HF), including disease not captured by left ventricular ejection fraction (LVEF), but the cardiac phenotypes underlying model predictions remain unclear. We therefore investigated whether AI-ECG-predicted HF risk aligns with established echocardiographic measures of myocardial dysfunction, remodelling, and filling pressures. We retrospectively analysed ECG and echocardiography data from 8147 patients who underwent both examinations within three days at Akershus University Hospital between 1 January 2023 and 1 June 2025. A previously validated AI-ECG model for HF detection was applied to all ECGs. Spearman's rank correlation $ρ$ quantified associations between echocardiographic parameters and AI-ECG risk. Subgroup analyses were performed by sex and left ventricular ejection fraction (LVEF). External validation included 36,286 ECG-echocardiography pairs from Columbia University Irving Medical Center. Global longitudinal strain (GLS) showed the strongest correlation ($ρ$=0.57), followed by mitral annular plane systolic excursion (MAPSE) ($ρ$=-0.49) and LVEF ($ρ$=-0.45). In patients with LVEF>50%, correlations remained substantial for GLS, MAPSE, and diastolic-related parameters. Volumetric left ventricular indices correlated less strongly in women, whereas diastolic indices showed stronger correlations in women than in men. Physiological validation showed that AI-ECG HF risk predictions align primarily with measures of systolic function, particularly global longitudinal strain, while also capturing diastolic-related abnormalities in patients with preserved LVEF. This approach may improve clinical interpretability and identify opportunities for model refinement.