LAUSR

Objective Heart failure with mildly reduced ejection fraction (HFmrEF) has been recently recognized as a unique phenotype of heart failure (HF) in current practical guideline. However, risk stratification models for mortality and HF re-hospitalization are still lacking. This study aimed to develop and validate a novel machine learning (ML)-derived model to predict the risk of mortality and re-hospitalization for HFmrEF patients. Methods We assessed the risks of mortality and HF re-hospitalization in HFmrEF (45–49%) patients enrolled in the TOPCAT trial. Eight ML-based models were constructed, including 72 candidate variables. The Harrell concordance index (C-index) and DeLong test were used to assess discrimination and the improvement in discrimination between models, respectively. Calibration of the HF risk prediction model was plotted to obtain bias-corrected estimates of predicted versus observed values. Results Least absolute shrinkage and selection operator (LASSO) Cox regression was the best-performing model for 1- and 6-year mortality, with a highest C-indices at 0.83 (95% CI: 0.68–0.94) over a maximum of 6 years of follow-up and 0.77 (95% CI: 0.64–0.89) for the 1-year follow-up. The random forest (RF) showed the best discrimination for HF re-hospitalization, scoring 0.80 (95% CI: 0.66–0.94) and 0.85 (95% CI: 0.71–0.99) at the 6- and 1-year follow-ups, respectively. For risk assessment analysis, Kansas City Cardiomyopathy Questionnaire (KCCQ) subscale scores were the most important predictor of readmission outcome in the HFmrEF patients. Conclusion ML-based models outperformed traditional models at predicting mortality and re-hospitalization in patients with HFmrEF. The results of the risk assessment showed that KCCQ score should be paid increasing attention to in the management of HFmrEF patients. Graphical Abstract In this study, we first selected heart failure patients whose LVEF was 45–49%. We then developed eight machine learning-based prediction models for the outcomes of all-cause mortality and HF rehospitalization. We selected the best-performing prediction model for different outcomes and then further demonstrated the risk factors involved.