Metabolic dysfunction–associated steatotic liver disease and heart failure with preserved ejection fraction: mechanisms and clinical implications from a heart–liver metabolic axis perspective

Metabolic dysfunction–associated steatotic liver disease (MASLD) and heart failure with preserved ejection fraction (HFpEF) are increasingly prevalent cardiometabolic disorders that frequently coexist in clinical practice. Growing evidence indicates that MASLD is associated with an increased risk of heart failure, with emerging data suggesting particular relevance to the HFpEF phenotype. This relationship is supported by several shared pathophysiological mechanisms, including insulin resistance, lipotoxicity, chronic low-grade inflammation, neurohormonal activation, microvascular dysfunction, fibrotic remodeling, and dysregulation of the gut–heart–liver axis, collectively supporting the concept of a heart–liver metabolic axis linking hepatic and cardiac injury. Clinically, MASLD, especially when accompanied by a greater fibrosis burden, may help identify a metabolically enriched HFpEF subgroup characterized by more advanced systemic derangement and organ remodeling. Although lifestyle intervention, sodium–glucose cotransporter 2 (SGLT2) inhibitors, incretin-based therapies, and liver-directed treatments have broadened the therapeutic framework for this overlap phenotype, prospective evidence specifically addressing patients with coexisting MASLD and HFpEF remains limited. This review summarizes the epidemiological links, shared mechanisms, risk stratification approaches, and therapeutic strategies relevant to the coexistence of MASLD and HFpEF.