Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF
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Aims: To date, clinical evidence of microvascular dysfunction in patients with heart failure (HF) with preserved ejection fraction (HFpEF) has been limited. We aimed to investigate the prevalence of coronary microvascular dysfunction (CMD) and its association with systemic endothelial dysfunction, HF severity, and myocardial dysfunction in a well defined, multi-centre HFpEF population. Methods and results: This prospective multinational multi-centre observational study enrolled patients fulfilling strict criteria for HFpEF according to current guidelines. Those with known unrevascularized macrovascular coronary artery disease (CAD) were excluded. Coronary flow reserve (CFR) was measured with adenosine stress transthoracic Doppler echocardiography. Systemic endothelial function [reactive hyperaemia index (RHI)] was measured by peripheral arterial tonometry. Among 202 patients with HFpEF, 151 [75% (95% confidence interval 69-81%)] had CMD (defined as CFR <2.5). Patients with CMD had a higher prevalence of current or prior smoking (70% vs. 43%; P = 0.0006) and atrial fibrillation (58% vs. 25%; P = 0.004) compared with those without CMD. Worse CFR was associated with higher urinary albumin-to-creatinine ratio (UACR) and NTproBNP, and lower RHI, tricuspid annular plane systolic excursion, and right ventricular (RV) free wall strain after adjustment for age, sex, body mass index, atrial fibrillation, diabetes, revascularized CAD, smoking, left ventricular mass, and study site (P < 0.05 for all associations). Conclusions: PROMIS-HFpEF is the first prospective multi-centre, multinational study to demonstrate a high prevalence of CMD in HFpEF in the absence of unrevascularized macrovascular CAD, and to show its association with systemic endothelial dysfunction (RHI, UACR) as well as markers of HF severity (NTproBNP and RV dysfunction). Microvascular dysfunction may be a promising therapeutic target in HFpEF.
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Obesity and diabetes create a pro-inflammatory state and promote endothelial and coronary microvascular dysfunction.
“Obesity and diabetes create a pro-inflammatory state and promote endothelial and coronary microvascular dysfunction. 1,7,8”
From Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials (2024) · cites this paper as [8]
The Introduction (page not specified) describes a hypothesis that obesity and diabetes, among other HFpEF comorbidities, lead to systemic and coronary endothelial inflammation and coronary microvascular dysfunction. The claim presents that proposed pathway as an established causal fact and does not retain its HFpEF context. (LLM, conf=0.86)
Experimental — accuracy not yet measuredInhibition of systemic metabolic inflammation with glucose-lowering drugs is thought to enhance endothelial and cardiomyocyte function.
“Inhibition of systemic metabolic inflammation with glucose-lowering drugs is thought to enhance endothelial and cardiomyocyte function”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [72]
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Sex Differences in Heart Failure With Preserved Ejection Fraction Pathophysiology
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Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction
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Immunometabolic mechanisms of heart failure with preserved ejection fraction
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Macrophages in Heart Failure with Reduced versus Preserved Ejection Fraction
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Inflammation in Metabolic Cardiomyopathy
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Cardiovascular Imaging Techniques to Assess Microvascular Dysfunction
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Coronary Microvascular Disease in Contemporary Clinical Practice
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Metabolomic Profile in HFpEF vs HFrEF Patients
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Reduced lymphatic reserve in heart failure with preserved ejection fraction
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Lipotoxicity: a driver of heart failure with preserved ejection fraction?
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Heart failure with preserved ejection fraction based on aging and comorbidities
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Comorbidities in heart failure with preserved ejection fraction
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The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF
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Non-coding RNAs as therapeutic targets and biomarkers in ischaemic heart disease
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Prioritising the primary prevention of heart failure
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Myocardial Energetics in Heart Failure With Preserved Ejection Fraction
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Cardiovascular Benefits from Gliflozins: Effects on Endothelial Function
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Endothelial cell dysfunction in cardiac disease: driver or consequence?
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Sex Differences in Cardiovascular Aging and Heart Failure
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The NO-cGMP-PKG Axis in HFpEF: From Pathological Mechanisms to Potential Therapies
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Metabolic and Immune Crosstalk in Cardiovascular Disease
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Sex-Based Differences in Heart Failure
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The vasculature: a therapeutic target in heart failure?
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Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging
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Endothelium in Coronary Macrovascular and Microvascular Diseases
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2026 ESC Guidelines for the management of heart failure
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- Authors
- Shah, S. J., Lam, C. S. P., Svedlund, S., Saraste, A., Hage, C., Tan, R.-S., Beussink-Nelson, L., Ljung Faxén, U., Fermer, M. L., Broberg, M. A., Gan, L.-M., & Lund, L. H.
- Affiliations
- Northwestern University (US)
- University Medical Center Groningen (NL)
- Sahlgrenska University Hospital (SE)
- University of Turku (FI)
- Karolinska Institutet (SE)
- National University of Singapore (SG)
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- Department of Medicine, Cardiology Unit and Heart and Vascular Theme, Karolinska Institutet, Stockholm, Sweden
- Early Clinical Development, IMED Biotech Unit, AstraZeneca Gothenburg, Sweden
- AstraZeneca (Sweden) (SE)
- Corresponding author
- Gan, Li-Ming
- Lund, Lars H
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-08-27
- Volume
- 39
- Issue
- 37
- Pages
- 3439-3450
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- PMC
- PMC6927847
- OpenAlex
- W2889002990
- Cited by
- 656
- References
- 45
- Citations by year
- 2026: 79 · 2025: 91 · 2024: 100 · 2023: 98 · 2022: 93 · 2021: 73 · 2020: 67 · 2019: 48 · 2018: 5 · 2013: 1
- FWCI
- 36.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- European Heart Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- NIH
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- heart failure with preserved ejection fraction, coronary microvascular dysfunction, coronary flow reserve, endothelial dysfunction, reactive hyperaemia index, albumin-creatinine ratio, NT-proBNP, right ventricular dysfunction, atrial fibrillation, smoking, prevalence
- MeSH terms
- Aged, Aged, 80 and over, Coronary Vessels, Female, Humans, Male, Middle Aged, Prospective Studies, Echocardiography, Doppler, Heart Failure, Diastolic, Microvessels
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