Interpretable Machine Learning Models Using Peripheral Immune Cells to Predict 90-Day Readmission or Mortality in Acute Heart Failure Patients

Background Acute heart failure (AHF) carries a grave prognosis, marked by high readmission and mortality rates within 90 days post-discharge. This underscores the urgent need for enhanced care transitions, early monitoring, and precise interventions for at-risk individuals during this critical period. Objective Our study aims to develop and validate an interpretable machine learning (ML) model that integrates peripheral immune cell data with conventional clinical markers. Our goal is to accurately predict 90-day readmission or mortality in patients AHF. Methods In our study, we conducted a retrospective analysis on 1210 AHF patients, segregating them into training and external validation cohorts. Patients were categorized based on their 90-day outcomes post-discharge into groups of ‘with readmission/mortality’ and ‘without readmission/mortality’. We developed various ML models using data from peripheral immune cells, traditional clinical indicators, or both, which were then internally validated. The feature importance of the most promising model was examined through the Shapley Additive Explanations (SHAP) method, culminating in external validation. Results In our cohort of 1210 patients, 28.4% (344) faced readmission or mortality within 90 days post-discharge. Our study pinpointed 10 significant indicators—spanning peripheral immune cells and traditional clinical metrics—that predict these outcomes, with the support vector machine (SVM) model showing superior performance. SHAP analysis further distilled these predictors to five key determinants, including three clinical indicators and two immune cell types, essential for assessing 90-day readmission or mortality risks. Conclusion Our analysis identified the SVM model, which merges traditional clinical indicators and peripheral immune cells, as the most effective for predicting 90-day readmission or mortality in AHF patients. This innovative approach promises to refine risk assessment and enable more targeted interventions for at-risk individuals through continuous improvement.