Sex Differences in Heart Failure: Toward Precision Medicine

Heart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality worldwide, with an estimated prevalence projected to exceed 8.5 million cases in the United States by 2030. Despite similar lifetime risk between sexes, men and women exhibit profoundly distinct clinical phenotypes, pathophysiological substrates, and therapeutic responses. Women more frequently develop HF with preserved ejection fraction (HFpEF), predominantly of non-ischemic etiology, while men more often present with HF with reduced ejection fraction (HFrEF) of ischemic origin. These differences have direct implications for diagnosis, risk stratification, and therapeutic management. This critical review analyzes the main available evidence on sex and gender differences in HF, with particular attention to pathophysiological bases, disparities in the diagnostic-therapeutic pathway, and unresolved gaps in clinical research.