Heart failure with preserved ejection fraction: the role of microvascular dysfunction

Abstract

Aim. To evaluate the relationship between coronary microvascular dysfunction (CMD), biomarkers of cardiac fibrosis and cardiac remodeling (soluble ST2 (sST2), fibroblast growth factor-23 (FGF-23), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and NT-proBNP), parameters of diastolic dysfunction (DD), and the presence of heart failure with preserved ejection fraction (HFpEF) in symptomatic patients.Materials and methods. Study participants were 59 patients with non-obstructive coronary artery disease (CAD) and preserved left ventricular ejection fraction (LVEF) of 62 (56; 67) %. Non-obstructive CAD was verified by coronary computed tomography angiography. Stress-and rest-myocardial blood flow (MBF) and coronary flow reserve (CFR) parameters were evaluated by CZT SPECT. Serum levels of cardiac biomarkers were measured by the enzyme immunoassay. Two-dimensional transthoracic echocardiography was used to assess DD parameters.Results. Decreased CFR was defined as CFR ≤ 2. Therefore, CMD was defined as the presence of decreased CFR in the absence of flow-limiting CAD. Distribution of patients was performed by CFR values: group 1 included patients with preserved CFR (>2, n = 35), and group 2 encompassed patients with decreased CFR (≤2, n = 24). In 87.5% of cases, patients with CMD were diagnosed with HFpEF, whereas in patients with preserved CFR, heart failure was diagnosed only in 51.4% of cases (p < 0.0001). CFR values were correlated with the left atrial volume (r = –0.527; p = 0.001), E / A ratio (r = –0.321, p = 0.012), and E / e’ (r = –0.307; p = 0.021). Following the ROC analysis, the levels of sST2 ≥ 31.304 ng / ml (AUС = 0.730; р = 0.004) and NT-proBNP ≥ 0.034 pg / ml (AUС = 0.815; р = 0.034) were identified as cut-off values for the presence of CMD in patients with non-obstructive CAD.Conclusion. The obtained data suggest that CMD may play an essential role in HFpEF. The values of CFR were correlated with DD parameters, and decreased CFR was associated with overexpression of biomarkers of cardiac fibrosis and cardiac remodeling. Serum levels of sST2 and NT-proBNP were identified as cut-off values for the presence of CMD in patients with non-obstructive CAD.