Empagliflozin–pirfenidone dual therapy improves cardiac function and structure in a preclinical two-hit HFpEF model

BackgroundHeart failure with preserved ejection fraction (HFpEF) accounts for more than half of heart failure cases and is associated with substantial morbidity and mortality. Although sodium–glucose cotransporter-2 inhibitors (SGLT2is) have shown efficacy in reducing HFpEF hospitalizations, the disease’s multi-pathway pathogenesis often limits the effectiveness of single-target interventions. This study examines whether the cardiovascular benefits of empagliflozin (EMPA) can be synergistically