Does Characterization of Phenotypic Heterogeneity Provide Mechanistic Insights or Influence the Response to Treatment? Experience in Positive and Neutral Trials in Patients With Heart Failure and a Preserved Ejection Fraction

The authors investigate whether the characterization of phenotypic heterogeneity in heart failure with preserved ejection fraction (HFpEF) can provide mechanistic insights or improve treatment responses. They find that despite extensive efforts to define phenotypic diversity, these approaches have not successfully identified effective treatment responders or novel therapeutic pathways. Instead, large-scale trials have demonstrated the efficacy of certain treatments across a broadly defined patient population, suggesting that a unifying hypothesis for HFpEF may render detailed phenotypic characterization unnecessary.