Heart Failure with Supranormal Ejection Fraction: A Female-Predominant Syndrome

Heart failure (HF) with supranormal ejection fraction (EF) has emerged as a distinct clinical entity that challenges traditional understanding of HF classification. This condition, characterized by left ventricular EF (LVEF) exceeding 65–70%, demonstrates unique pathophysiological mechanisms and carries significant clinical implications, particularly in women. Recent studies have revealed that supranormal LVEF (snLVEF) follows a U-shaped mortality curve, with risk levels comparable to those seen in reduced EF. The condition shows notable gender dimorphism, with women showing higher baseline EFs and distinct cardiac remodeling patterns. Pathophysiological mechanisms include microvascular dysfunction, sympathetic hyperactivation, and gender-specific cardiac adaptations influenced by hormonal factors and body composition. Genetic studies have identified specific variants associated with snLVEF, suggesting a distinct genetic phenotype. While traditional HF medications have shown limited efficacy, newer agents such as dapagliflozin and semaglutide demonstrate promising results. Understanding this condition’s unique characteristics is crucial for developing targeted therapeutic approaches and improving patient outcomes.