Abstract
Whether there is a subset of patients with heart failure with preserved ejection fraction (HFpEF) that benefit from spironolactone therapy is unclear. We applied a machine learning approach to identify responders and non-responders to spironolactone among patients with HFpEF in two large randomized clinical trials. Using a reiterative cluster allocating permutation approach, patients from the derivation cohort (Aldo-DHF) were identified according to their treatment response to spironolactone with respect to improvement in E/e'. Heterogenous features of response ('responders' and 'non-responders') were characterized by an extreme gradient boosting (XGBoost) algorithm. XGBoost was used to predict treatment response in the validation cohort (TOPCAT). The primary endpoint of the validation cohort was a combined endpoint of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Patients with missing variables for the XGboost model were excluded from the validation analysis. Out of 422 patients from the derivation cohort, reiterative cluster allocating permutation identified 159 patients (38%) as spironolactone responders, in whom E/e' significantly improved (p=0.005). Within the validation cohort (n=525) spironolactone treatment significantly reduced the occurrence of the primary outcome among responders (n=185, p log rank=0.008), but not among patients in the non-responder group (n=340, p log rank=0.52). Machine learning approaches might aid in identifying HFpEF patients who are likely to show a favorable therapeutic response to spironolactone. See Acknowledgements section at the end of the manuscript.
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