Heart failure with preserved ejection fraction in women: a sex-specific clinical review

Heart failure with preserved ejection fraction (HFpEF) affects approximately half of the current heart failure population and demonstrates marked sex-related differences in pathophysiology, clinical presentation, and therapeutic response. These distinctions reflect the divergent biological pathways that shape disease expression in women and men. In women, disease expression is frequently linked to cardiometabolic stress, vascular dysfunction, and heightened ventricular-arterial coupling, often manifesting as concentric remodeling and a pronounced symptom burden. By contrast, men more commonly exhibit an ischemia-associated phenotype characterized by adverse remodeling and diffuse myocardial fibrosis. These biological differences influence the clinical presentation, biomarker interpretation, imaging findings, and long-term outcomes. Although most pharmacological therapies demonstrate broadly comparable efficacy between sexes, selected neurohormonal interventions and lifestyle-based strategies may yield differential benefits, underscoring the importance of sex- and phenotype-informed management. The recognition of sex-related heterogeneity in HFpEF may refine diagnostic algorithms, improve therapeutic targeting, and inform the design of future precision-based clinical trials.