Sex and Gender Differences in Heart Failure with Preserved Ejection Fraction: From Pathophysiology to Modern Therapeutic Guidelines

Q: What is the clinical evidence from this study?

Study design: Review. Population: Heart failure with preserved ejection fraction (HFpEF). Intervention: Female sex vs. Male sex.

Kristina Gašparović

doi:10.15836/ccar2026.248

November 1, 2026Cardiologia CroaticaOpen Access

Sex and Gender Differences in Heart Failure with Preserved Ejection Fraction: From Pathophysiology to Modern Therapeutic Guidelines

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Key Points

To systematically evaluate sex- and gender-specific differences in pathophysiology, diagnostic criteria, and therapeutic responses among patients with heart failure with preserved ejection fraction.
Targeted analysis of heart failure registries, the 2026 European Society of Cardiology Guidelines framework, and recent sex-stratified pooled meta-analyses.
Evaluation of modern medical therapies including SGLT2 inhibitors, GLP-1 receptor agonists, and angiotensin receptor neprilysin inhibitors (ARNIs).
Women comprise over 55–60% of the HFpEF population, presenting at an older age with lower quality-of-life scores and higher non-cardiovascular rehospitalization rates despite better age-adjusted survival.
The 2026 ESC Guidelines define sex-specific left ventricular hypertrophy thresholds at a left ventricular mass index ≥95 g/m² in women compared to ≥115 g/m² in men, while noting obesity can falsely suppress NT-proBNP levels.
While SGLT2 inhibitors provide Class I benefit across both sexes, women experience therapeutic benefit from sacubitril/valsartan up to higher ejection fraction ceilings (≤65%) than men and show marked functional improvement with GLP-1 agonists.

Structured PICO

P

Population

Patients with heart failure with preserved ejection fraction (LVEF ≥50%), where women constitute over 55–60% of the population.

E

Exposure

Modern medical therapies including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and angiotensin receptor neprilysin inhibitors (ARNIs, specifically sacubitril/valsartan)

O

Outcome

Sex- and gender-specific discrepancies in pathophysiology, diagnostic criteria, clinical phenotype, prognosis, and therapeutic responses

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Implication

This review highlights the importance of sex-specific diagnostic thresholds (such as LVMI ≥95 g/m² in women) and tailored pharmacotherapy (including SGLT2 inhibitors, sacubitril/valsartan up to LVEF ≤65% in women, and GLP-1 receptor agonists) in managing HFpEF according to the 2026 ESC Guidelines.

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Cite This Study

Kristina Gašparović (2026) conducted a review in Heart failure with preserved ejection fraction (HFpEF). Female sex vs. Male sex was evaluated.

synapsesocial.com/papers/6af88ddc0e4d8f4b089c1c89 https://doi.org/10.15836/ccar2026.248

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Sex and Gender Differences in Heart Failure with Preserved Ejection Fraction: From Pathophysiology to Modern Therapeutic Guidelines

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Sex and Gender Differences in Heart Failure with Preserved Ejection Fraction: From Pathophysiology to Modern Therapeutic Guidelines

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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