Send to

Choose Destination
Eur Heart J. 2018 Oct 1;39(37):3439-3450. doi: 10.1093/eurheartj/ehy531.

Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF.

Author information

Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
National Heart Centre Singapore, Duke-National University of Singapore, Singapore.
University Medical Centre Groningen, Groningen, the Netherlands.
Department of Clinical Physiology, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
Heart Center, Turku University Hospital, University of Turku, Turku, Finland.
Department of Medicine, Cardiology Unit and Heart and Vascular Theme, Karolinska Institutet, Stockholm, Sweden.
Early Clinical Development, IMED Biotech Unit, AstraZeneca Gothenburg, Sweden.
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.



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).


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.


Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center