Role of humoral markers in the pathogenesis of heart failure with preserved ejection fraction in patients with non-obstructive coronary artery disease

Aim. To study the role of molecular biomarkers potentially influencing the formation and progression of heart failure (HF) with preserved ejection fraction (HFpEF) in non-obstructive coronary artery disease (CAD).Material and methods. We examined 48 patients with newly diagnosed HFpEF against the background of non-obstructive CAD. Group 1 (n=31) included patients with class I-II HF and group 2 (n=17) included patients with class III HF; the control group consisted of patients without heart failure (n=17). The content of NT-proBNP and sST2, diastolic dysfunction and coronary flow reserve parameters were assessed.Results. The content of NT-proBNP in patients of group 1 was 45% higher than in group 2 (p<0,001). The mean levels of sST2 did not exceed the reference values and significantly exceeded the control group (p<0,001). Coronary flow reserve (CFR) decreased (p<0,001) depending on the severity of HF. Negative associations of sST2 levels with LVEF, septal e’ and CFR were revealed, as well as NT-proBNP with CFR.Conclusion. HFpEF in non-obstructive CAD is triggered due to progressive impairment of endothelial function, which affects the decrease in coronary and myocardial flow reserves, diastolic function, hyperproduction of humoral factors that initiate perivascular fibrosis and apoptosis of cardiomyocytes

Coronary flow reserve in patients with heart failure with preserved ejection fraction

Aim. To study the parameters of myocardial blood flow (MBF) and coronary flow reserve (CFR) in patients with heart failure (HF) with preserved ejection fraction and evaluate their relationship with the severity of HF.Material and methods. The study included 47 patients (men, 68,7%) aged 65,0 (58,0; 72,0) years with left ventricular ejection fraction of 62 (56; 67)% and coronary artery stenosis <50%. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were assessed by enzyme immunoassay. MBF and CFR values were assessed using cardiac single photon emission computed tomography.Results. Depending on NT-proBNP levels, the patients were divided into 2 groups (p<0,001): the 1st group included (n=15) patients with NT-proBNP <125 pg/ml (58,2 [41,6; 70,7] pg/ml), while in the 2nd group (n=32) — with NT-proBNP ≥125 pg/ml (511,4 [249,8; 1578,1] pg/ml). The group of patients with high NTproBNP levels was characterized by higher values (by 33,8%, p=0,0001) of resting MBF and reduced CFR (by 14,7%, p=0,001) compared with patients with normal NT-proBNP level: resting MBF — 0,65 (0,44; 0,79) vs 0,43 (0,30; 0,58) ml/min/g; CFR — 2,21 (1,52; 2,83) vs 2,59 (2,47; 3,05), respectively. At the same time, MBF at stress did not differ between the groups. The relationship of NTproBNP levels with global CFR (p=0,012; r=-0,339) and MBF at rest (p=0,012; r=0,322) was established. A stepwise decrease in global CFR was revealed depending on the NYHA class as follows (p<0,001): 2,79 (2,52; 2,93); 1,8 (1,55; 2,08); 1,31 (1,23; 1,49) — for class I, II, and III, respectively.Conclusion. A decrease in CFR in patients with HF with preserved ejection fraction indicates impaired myocardial blood supply, which, in this group of patients, is associated with microcirculatory changes. At the same time, the severity of MBF alterations is closely related to HF severity

Association of impaired myocardial flow reserve with risk factors for cardiovascular diseases in patients with nonobstructive coronary artery disease

Aim. To reveal the association between disorders of myocardial blood flow and reserve, according to dynamic single photon emission computed tomography (SPECT), with risk factors for cardiovascular diseases (CVD) in patients with nonobstructive coronary artery disease (CAD).Material and methods. The study included patients with suspected stable nonobstructive (<50%) CAD. Based on the survey data, anamnesis, out- and in-patient medical records, we analyzed main CVD risk factors. All patients underwent dynamic myocardial SPECT and analysis of blood lipid profile in vitro. Depending on myocardial flow reserve (MFR), two groups were formed: 1. With reduced MFR <2,0 (rMFR); 2. With normal MFR ≥2,0 (nMFR).Results. The study included 47 patients divided into 2 following groups: the rMFR group consisted of 24 patients (15 men, age 56,3±9,1 years), the nMFR group — 23 patients (13 men, age 58,4±10,7 years). There was no significant difference in prevalence of CVD risk factors in groups. However, dyslipidemia was detected more often in rMFR patients (p=0,053): 58% vs 30%, respectively. In patients with rMFR, there were significantly higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Correlation analysis revealed significant negative inverse relationships between MFR values with TC (ρ=-0,36, p=0,01) and LDL-C (ρ=-0,38, p=0,009). According to univariate logistic regression, significant predictors of reduced MFR were TC (odds ratio (OR), 2,32; 95% confidence interval (CI), 1,17-4,59; p=0,01) and LDL-C (OR, 2,16; 95% CI, 1,04-4,51; p=0,04). According to a stepwise multivariate logistic regression analysis, only TC was an independent predictor of a decrease in MFR (OR, 2,32; 95% CI, 1,17-4,59; p=0,02).Conclusion. MFR, determined by dynamic SPECT, is associated with TC and LDL-C levels. TC level is an independent predictor of a decrease in MFR