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Heart Failure Treatment and Management · Journal article
International Journal of Drug Discovery and Pharmacology · September 4, 2026
Raises a question worth testing. It does not answer one.
This is a narrative review synthesizing known sex differences in HFpEF epidemiology, phenotype, and putative mechanisms. It does not present new empirical evidence, clinical trial results, or direct comparison of outcomes or therapeutic responses, but rather proposes a framework linking hormonal, chromosomal, and molecular pathways to sex-specific disease manifestations. The source identifies opportunities for sex-informed therapeutic targeting but does not provide evidence that any such strategy improves clinical outcomes.
Narrative review. Patients with heart failure with preserved ejection fraction (HFpEF), with emphasis on age-related and sex-based differences; predominantly older women and men with distinct comorbidity and phenotype profiles..
HFpEF accounts for more than half of heart failure cases and disproportionately affects older women Women more commonly exhibit concentric left ventricular remodeling and diastolic dysfunction, frequently with obesity, hypertension, diabetes, and anemia Men more often present with ischemic heart disease, renal dysfunction, and right ventricular involvement
No quantitative efficacy or safety data for any therapeutic intervention
Clinicians should recognize that HFpEF presents with distinct phenotypes and comorbidity patterns in women versus men, and that therapeutic responses may differ by sex. However, this review does not provide evidence to change current treatment decisions; it identifies pathways and phenotypes that warrant further investigation and sex-stratified clinical trials.
A narrative review synthesizing mechanistic concepts and observational patterns in sex differences in HFpEF, raising questions about pathophysiology rather than presenting empirical evidence of efficacy or harm.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should recognize that HFpEF presents with distinct phenotypes and comorbidity patterns in women versus men, and that therapeutic responses may differ by sex. However, this review does not provide evidence to change current treatment decisions; it identifies pathways and phenotypes that warrant further investigation and sex-stratified clinical trials.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that accounts for more than half of heart failure cases and disproportionately affects older women. Biological sex is a key determinant of HFpEF, influencing epidemiology, comorbidity profiles, cardiac structure, clinical outcomes, and therapeutic responses. Women more commonly exhibit concentric left ventricular remodeling and diastolic dysfunction, frequently in association with obesity, hypertension, diabetes, and anemia, whereas men more often present with ischemic heart disease, renal dysfunction, and right ventricular involvement. These sex differences extend to prognosis, quality of life, and responses to therapies such as spironolactone and sacubitril/valsartan. At the mechanistic level, women exhibit greater metabolic dysregulation, heightened inflammatory responses, and more pronounced ventricular–arterial stiffening, whereas men show more prominent ischemic and cardiorenal perturbations. Emerging evidence indicates that these sex-specific features arise from distinct but interconnected pathophysiological pathways, including mitochondrial dysfunction, renin–angiotensin–aldosterone system (RAAS) imbalance, microvascular inflammation, impaired NO–cGMP–PKG signaling, and extracellular matrix remodeling. These pathways are differentially regulated by gonadal hormones, sex chromosome dosage, and X-linked gene escape from inactivation, which together shape cardiac stiffness, fibrosis, oxidative stress, and immune activation. Overall, these findings highlight the complex interplay between hormonal, chromosomal, and molecular mechanisms underlying sex differences in HFpEF. A better understanding of these processes may help explain disease heterogeneity, guide the rational identification of sex-dependent therapeutic targets, and support the development of sex-informed prevention and therapeutic strategies.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.