HFpEF demonstrates marked sex-related differences in pathophysiology, clinical presentation, and therapeutic response, with women more frequently exhibiting cardiometabolic stress, vascular dysfunction, and concentric remodeling, while men more commonly show an ischemia-associated phenotype with adverse remodeling and diffuse myocardial fibrosis.
HFpEF affects approximately half of the current heart failure population and shows marked sex-related differences across multiple disease dimensions.
Women with HFpEF more frequently exhibit a cardiometabolic and vascular dysfunction phenotype characterized by concentric remodeling and pronounced symptom burden.
Men with HFpEF more commonly exhibit an ischemia-associated phenotype characterized by adverse remodeling and diffuse myocardial fibrosis.
Biological sex differences in HFpEF influence clinical presentation, biomarker interpretation, imaging findings, and long-term outcomes.
Most pharmacological therapies for HFpEF demonstrate broadly comparable efficacy between sexes, but selected neurohormonal interventions and lifestyle-based strategies may yield differential benefits by sex.
Recognition of sex-related heterogeneity in HFpEF has potential implications for diagnostic algorithms, therapeutic targeting, and future clinical trial design.
This review paper examines how heart failure with preserved ejection fraction (HFpEF) — a type of heart failure where the heart pumps normally but is too stiff to fill properly — differs between women and men. HFpEF affects roughly half of all heart failure patients, and until recently, research has largely treated it as a single condition without accounting for how differently it behaves based on sex. This research suggests that women and men tend to develop HFpEF through different biological pathways, leading to different structural changes in the heart, different symptoms, and potentially different responses to treatment. Specifically, this research suggests that women with HFpEF more commonly develop problems related to metabolic stress, blood vessel dysfunction, and changes in how the heart and arteries interact, often resulting in a heart that becomes thickened and compact (concentric remodeling) and a heavier burden of symptoms. Men, on the other hand, are more likely to have HFpEF driven by reduced blood supply to the heart muscle, with more extensive scarring of the heart tissue. These differences also affect how blood markers and imaging results should be interpreted, and they influence long-term health outcomes. From a treatment standpoint, this research suggests that while most heart failure medications work similarly in both sexes, some hormone-targeting therapies and lifestyle interventions may work better in one sex than the other. The authors argue that taking sex into account when diagnosing and treating HFpEF could lead to more personalized, effective care — and that future clinical trials should be designed with these sex differences in mind rather than assuming results apply equally to everyone.
Kim S, Shin M. (2026). Heart failure with preserved ejection fraction in women: a sex-specific clinical review.. The Korean journal of internal medicine. https://doi.org/10.3904/kjim.2026.086