Multimodal Visualization and Explainable Machine Learning–Driven Markers Enable Early Identification and Prognosis Prediction for Symptomatic Aortic Stenosis and Heart Failure With Preserved Ejection Fraction After Transcatheter Aortic Valve Replacement: Multicenter Cohort Study (Preprint)

BACKGROUND Currently, there is a paucity of literature addressing personalized risk stratification using multimodal data in patients with symptomatic aortic stenosis and heart failure with preserved ejection fraction (HFpEF) following transcatheter aortic valve replacement (TAVR). OBJECTIVE This study aimed to enhance the performance of risk assessment models in this patient population by developing a predictive model for adverse outcomes using various machine learning (ML) techniques. METHODS This multicenter cohort study included 326 patients diagnosed with severe AS and HFpEF who underwent TAVR between January 2017 and December 2023. Patients were allocated to training (n=195) and independent validation (n=131) sets based on hospital affiliation. A dual-phase feature selection process, combining least absolute shrinkage and selection operator logistic regression and the Boruta algorithm, was used to identify relevant variables from the multimodal dataset. A total of 5 ML model-decision trees, K-nearest neighbors, random forest, support vector machine, and extreme gradient boosting were used to construct a visualization and explainable predictive framework to elucidate model decision-making processes. RESULTS The primary features identified included age, N-terminal pro-brain natriuretic peptide, fasting blood glucose, triglyceride/high-density lipoprotein cholesterol ratio, triglyceride glucose index, triglyceride glucose-BMI index, atherogenic index of plasma index, and Apolipoprotein B. Among the 5 models, the support vector machine demonstrated the best predictive performance for major adverse cardiovascular and cerebrovascular events in patients with severe AS and HFpEF following TAVR, achieving an area under the curve of 0.756 (95% CI 0.631-0.881) in the independent validation set. The model exhibited good calibration and robust predictive power in both training and validation sets and demonstrated the highest net benefit in decision curve analysis compared to other models. To extract significant variables influencing the algorithm and ensure model appropriateness, we interpreted cohort and personalized model predictions using Shapley Additive Explanations values. CONCLUSIONS Our ML-based multimodal model, incorporating 8 readily accessible predictors, demonstrated robust predictive capability for 12 months of major adverse cardiovascular and cerebrovascular events risk. This model can be used to identify high-risk individuals with AS and HFpEF following TAVR, potentially aiding in risk stratification and personalized treatment strategies.