Irina Cabac-Pogorevici, Iuliana Creangă, Inessa Jitari, Dmitri Savca, Valentin Avram, Alexandru Corlăteanu, Valeriu Revenco
Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, affecting women and men in nearly equal numbers, yet important sex- and gender-related differences remain insufficiently recognized in clinical practice and research. Biological sex and gender influences profoundly the disease development, clinical presentation, diagnosis and management. For decades, most evidence and guideline recommendations have been based on predominantly male cohorts, limiting their applicability to women. This review aims to synthesize the current evidence on sex- and gender-related differences in HF. Also, it integrates data from experimental studies, clinical trials, large registries, and recent guidelines, emphasizing differences in phenotype, biomarker profiles, pharmacologic responses, and access to device-based therapies. Despite better survival, women report greater symptom burden, poorer quality of life, and lower use of optimal medical or device therapy, including lower use of guideline-directed medical therapy and device-based interventions. Pharmacokinetic and pharmacodynamic differences suggest that women may achieve comparable therapeutic benefit at lower medication doses, yet guidelines remain largely sex-neutral. Thus, recognizing these biological and sociocultural distinctions is essential for precision and equity in care, improving diagnostic accuracy, optimizing therapeutic strategies and ensuring equity in cardiovascular care, advancing truly individualized cardiovascular medicine.