High prevalence of coronary microvascular dysfunction in patients with HFpEF
Introduction and methods
Preclinical data suggest that coronary microvascular dysfunction (CMD) contributes to the development of heart failure with preserved ejection fraction (HFpEF), through various mechanisms including the reduction of endothelial nitric oxide bioavailability and cyclic guanosine monophosphate production, resulting in increased cardiomyocyte stiffening, hypertrophy, and fibrosis [1-3]. Clinical evidence supporting this hypothesis, is, however, scarce, and the prevalence of CMD in HFpEF is unknown.
The prospective PROMIS-HFpEF (PRevalence Of Microvascular dySfunction in Heart Failure with Preserved Ejection Fraction) study assessed the prevalence of impaired coronary flow reserve (CFR) in HFpEF, and explored possible correlates, such as systemic endothelial dysfunction (reactive hyperemia index: RHI, urinary albumin-to-creatinine ratio: UACR), clinical factors, laboratory markers, and echocardiographic indices. For this purpose, detailed echocardiography and adenosine-based transthoracic Doppler echocardiography-assessed CFR measurements were combined in HFpEF patients. CMD was defined as a coronary flow velocity ratio of <2.5 .
Eligible patients had a prior history of symptomatic HF, NYHA Class II–IV symptoms, an EF ≥40%, and at least one of the following:
- elevated natriuretic peptides (NTproBNP)
- prior HF hospitalization with evidence of either left ventricular hypertrophy or left atrial enlargement
- elevated pulmonary capillary wedge pressure at rest or with exercise
- E/e’ ratio >15
Patients with known unrevascularized macrovascular coronary artery disease were excluded.
- A total of 263 patients were enrolled, out of whom 202 (87%) underwent successful CFR testing. Of those 202 participants, 151 (74.8%; 95%CI: 68.7–80.8%) had evidence of CMD.
- The mean ± standard deviation of CFR in the study cohort was 2.13 ± 0.51, and the median CFR was 2.08 (25th–75th percentile: 1.78–2.50).
- Atrial fibrillation (AF) and smoking were associated with lower CFR values (beta-coefficient for AF: -0.17; 95%CI: -0.31 to -0.03; P=0.02; for smoking: -0.20; 95%CI: -0.34 to -0.05; P= 0.007).
- Lower CFR was associated with higher UACR, higher levels of natriuretic peptides, lower RHI, lower left ventricular global longitudinal strain, and a lower left atrial reservoir strain.
Impaired coronary microvascular function is highly prevalent in HFpEF patients and is associated with systemic endothelial dysfunction, as well as with markers of HF severity such as elevated NTproBNP and cardiac dysfunction.