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Heart Failure with Supranormal Ejection Fraction: An Emerging High-Risk Phenotype Within the Preserved Ejection
Andrea Sonaglioni1, Giulio Francesco Gramaglia2, Gian Luigi Nicolosi3
1Division of Cardiology, IRCCS MultiMedica, 20123 Milan, Italy.
Journal of Clinical Medicine
|July 28, 2026
Summary
Heart failure with supranormal ejection fraction (HFsnEF) is a distinct, high-risk heart failure phenotype. Patients with HFsnEF face worse outcomes than those with preserved ejection fraction (HFpEF), necessitating further research.
Area of Science:
- Cardiology
- Heart Failure Research
- Clinical Phenotyping
Background:
- Heart failure with supranormal ejection fraction (HFsnEF) is an emerging phenotype within the preserved ejection fraction spectrum.
- Its clinical characteristics, underlying mechanisms, and prognosis are not well understood.
Purpose of the Study:
- To systematically review and synthesize current knowledge on HFsnEF.
- To compare HFsnEF with conventional heart failure with preserved ejection fraction (HFpEF).
Main Methods:
- Systematic review adhering to PRISMA guidelines.
- Searched PubMed, Scopus, and EMBASE databases.
- Meta-analyses of mortality and hospitalization rates.
Main Results:
- HFsnEF patients showed distinct echocardiographic features (smaller LV volumes, higher EF) and unique ventricular-vascular properties.
- HFsnEF was associated with a higher prevalence of women and lower prevalence of coronary artery disease compared to HFpEF.
- Meta-analyses revealed significantly higher all-cause mortality and composite cardiovascular events in HFsnEF versus HFpEF.
Conclusions:
- HFsnEF represents a distinct, high-risk phenotype challenging traditional assumptions about ejection fraction and cardiovascular health.
- Further research with advanced imaging and hemodynamics is crucial for understanding and managing HFsnEF.
- Sodium-glucose cotransporter-2 inhibitors may offer therapeutic benefits in HFsnEF.
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