Machine Learning Applications for Risk Stratification in Heart Failure with Preserved Ejection Fraction: A New Era in Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is a prevalent and heterogeneous syndrome with limited therapeutic options, making accurate risk stratification essential yet challenging. Traditional tools such as the H2FPEF and HFA-PEFF scores incorporate few variables and demonstrate modest prognostic performance. Machine learning (ML) offers enhanced risk prediction by integrating multidimensional clinical, imaging, biomarker, and molecular data. This review summarizes current ML applications in HFpEF, including random forests, gradient boosting, support vector machines, and deep learning, highlighting their superior discrimination and ability to reveal phenotypic subgroups with distinct outcomes. We also address practical considerations such as interpretability, real-world validation, and integration into clinical workflows, as well as challenges related to data bias, generalizability, and regulatory requirements. Future opportunities include real-time clinical decision support, digital health integration, and interventional ML to guide personalized therapy. ML holds significant potential to advance precision care and improve outcomes in HFpEF.