CONFIDENT-HFpEF: a machine learning-based risk stratification for mortality and hospitalization using multimodal real-world data

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition with high morbidity and mortality. Accurate risk stratification is important for advancing drug development and improving clinical care. Methods: CONFIDENT is an observational, multi-cohort study across three centres in Europe and the USA. Patients with HFpEF, according to the HFA-PEFF criteria, with ≥ 2 years of follow-up, were included from 2013 to 2022. Data include electronic health records, lab tests, echocardiography, and electrocardiography. We developed machine learning-based prognostic models to predict all-cause mortality and heart failure (HF) hospitalization. Model performance was compared to the validated risk score and validated in an external cohort. Results: A total of 1208 patients were included in the study. The mean age was 72 ± 12, and the mean body mass index was 32 ± 9 kg/m ². The 2-year risk of HF hospitalization and all-cause mortality ranged from 13 to 44% and 9 to 19%, respectively. The all-cause mortality prognostic model achieved fair discrimination with a C-index of 0.68 [95% CI 0.62–0.74], and 0.71 [95% CI 0.64–0.78] in the training cohorts, and a good discrimination of 0.72 [95% CI 0.65–0.78] in the validation cohort but performed better than the PREDICT-HFpEF score (C-index: 0.66 [95% CI 0.54–0.72], P-value = .006; 0.65, [95% CI 0.55–0.72], P-value < .001 and 0.67 [95% CI 0.59–0.73], P-value = .036, respectively). Similar results were observed when compared to the Meta-Analysis Global Group In Chronic Heart Failure Risk Score (MAGGIC). The HF hospitalization model also outperformed both comparators, including MAGGIC+ natriuretic peptide. Conclusion: CONFIDENT prognostic models for all-cause mortality and HF hospitalization using routinely collected variables can reliably predict outcomes and potentially facilitate personalized care and trial recruitment strategies in HFpEF.