Background: Progressive myocardial remodeling (MR) in chronic heart failure (CHF) leads to aggravation of systolic dysfunction (SD) and clinical manifestations. Identification of metabolomic markers of these processes may help in the search for new therapeutic approaches aimed at achieving reversibility of MR and improving prognosis in patients with CHF. Methods: To determine the relationship between plasma acylcarnitine (ACs) levels, MR parameters and clinical characteristics, in patients with CHF of ischemic etiology (n = 79) and patients with coronary heart disease CHD (n = 19) targeted analysis of 30 ACs was performed by flow injection analysis mass spectrometry. Results: Significant differences between cohorts were found for the levels of 11 ACs. Significant positive correlations (r > 0.3) between the medium- and long-chain ACs (MCACs and LCACs) and symptoms (CHF NYHA functional class (FC); r = 0.31−0.39; p < 0.05); negative correlation (r = −0.31−0.34; p < 0.05) between C5-OH and FC was revealed. Positive correlations of MCACs and LCACs (r = 0.31−0.48; p < 0.05) with the left atrium size and volume, the right atrium volume, right ventricle, and the inferior vena cava sizes, as well as the pulmonary artery systolic pressure level were shown. A negative correlation between C18:1 and left ventricular ejection fraction (r = −0.31; p < 0.05) was found. However, a decrease in levels compared to referent values of ACs with medium and long chain lengths was 50% of the CHF-CHD cohort. Carnitine deficiency was found in 6% and acylcarnitine deficiency in 3% of all patients with chronic heart disease. Conclusions: ACs may be used in assessing the severity of the clinical manifestations and MR. ACs are an important locus to study in terms of altered metabolic pathways in patients with CHF of ischemic etiology and SD. Further larger prospective trials are warranted and needed to determine the potential benefits to treat patients with CV diseases with aberrate AC levels.

Aim To compare serum concentrations of tryptophane (Trp) and its metabolites in subjects with no cardiovascular disease (CVD) and patients with СVD, including arterial hypertension (AH) and ischemic heart disease (IHD). Material and methods   This study included 131 participants; 58 participants (11 of them with documented peripheral atherosclerosis) were included into the AH group, 46 participants were included into the IHD group, and 27 participants with no signs of CVD were included into the control group. Plasma concentrations of Trp and its metabolites were measured by high-performance liquid chromatography in combination with a triple quadrupole analyzer. Results   Comparison of the three study groups revealed significant differences in concentrations of Trp (р=0.029), kynurenine (p<0.001), kynurenine/Trp ratio (p<0.001), quinolinic acid (р=0.007), kynurenic acid (р=0.003), serotonin (p<0.001), and 5‑hydroxyindoleacetic acid (5‑HIAA) (р=0.011). When the AH group was subdivided into subgroups without and with documented peripheral atherosclerosis, the intergroup differences remained for concentrations of kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, serotonin, and 5‑HIAA. Also, correlations were found between concentrations of Trp metabolites and laboratory and instrumental data, primarily inflammatory markers. Conclusion   Analysis of serum concentrations of Trp and its metabolites in CVD patients showed increases in kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, and 5‑HIAA along with decreases in concentrations of Trp and serotonin in the groups of AH, AH with documented peripheral atherosclerosis, and IHD.

Aim To identify metabolomic and structure and function markers of remote left ventricular (LV) remodeling in patients with chronic heart failure (CHF) of ischemic etiology and LV ejection fraction (EF) <50%. Material and methods This prospective study included 56 patients with 3-4 NYHA functional class CHF of ischemic etiology (mean age, 66±7 years) and 50 patients with ischemic heart disease (IHD) without signs of CHF (69 [64; 73.7] years). Concentration of 19 amino acids, 11 products of kynurenine catabolism of tryptophan, 30 acylcarnitines with different chain lengths were measured in all participants. The metabolites that showed statistical differences between the comparison groups were then used for the analysis. Echocardiography was used to assess LV cavity remodeling at the time of the CHF patient inclusion in the study and after 6 months of follow-up. Predictors of long-term LV cavity remodeling were assessed for this cohort taking into account statistically significant echocardiographic parameters and metabolites. Results Patients with CHF of ischemic etiology, predominantly (81%) had pathological calculated types of LV remodeling (concentric and eccentric hypertrophy, 46 and 35%, respectively). However, this classification had limitations in describing this cohort. In addition, in this group, the concentrations of alanine, proline, asparagine, glycine, arginine, histidine, lysine, valine, indolyl-3-acetic acid, indolyl-3-propionic acid, C16-1-OH, and C16-OH were significantly (p<0.05) lower, and the concentrations of most medium- and long-chain acylcarnitines were higher than in patients with IHD without signs of CHF. The long-term (6 months) reverse remodeling of the LV cavity in CHF of ischemic etiology was influenced by changes in the interventricular septum thickness (hazard ratio, HR, 19.07; 95% confidence interval, CI, 1.76-206.8; p=0.006) and concentrations of anthranilic acid (HR 19.8; 95% CI 1.01-387.8; p=0.019) and asparagine (HR 8.76; 95% CI 1.07-71.4; p=0.031). Conclusion The presence of an interventricular septum thickness of more than 13.5 mm, anthranilic acid concentrations of higher than 0.235 μM/l, or an asparagine concentration of less than 135.2 μM/l in patients with CHF of ischemic etiology after 6 months of follow-up affects their achievement of LV cavity reverse remodeling.  

Aim. Branched-chain amino acids (BCAAs) have been postulated as potential indicators of cardiovascular risk. The objective of this study was to explore the relationship between plasma BCAAs and different stages of cardiovascular disorders.Material and methods. In our cross-sectional study, plasma BCAAs (valine, leucine and isoleucine) in individuals without cardiovascular diseases (CVDs) (nonCVD group, total n=27, with n=16 healthy, but with metabolic disorders) were compared to patients diagnosed with CVDs [CVD group, total n=109, being n=61 hypertension (n=31 with signs of beginning of myocardial remodeling) and n=48 patients with coronary artery disease (CAD)].Results. The plasma concentration of BCAAs was significantly higher in the group of patients with cardiovascular disease compared with the healthy group (p<0.05 for all amino acids tested): valine concentration was 238.7 [219.6; 267.0] μM in the non-CVD group and 261.2 [233.8; 298.7] μM in the CVD group; leucine concentration was 134.8 [122.4; 153.2] μM and 146.8 [129.0; 166.6] μM, respectively; and isoleucine 72.7 [65.3; 84.4] μM and 81.7 [68.0; 96.2] μM, respectively. Leucine and isoleucine concentration levels were minimal in the healthy participant subgroup and maximal in the IBS patient subgroup. No statistically significant differences in BCAAs concentrations were found in the subgroups without CAD. Significant increases in concentrations were observed in the subgroups of patients with CAD as follows: valine concentration was 256.3 [219.0; 297.9] μM in hypertension group and 261.7 [236.5; 307.5] μM in CAD group; leucine concentration was 141.8 [123.5; 166.6] μM and 154.1 [134.7; 172.7] μM, respectively, and isoleucine 72.8 [65.7; 94.0] μM and 85.7 [74.9; 101.7] μM, respectively. BCAAs profiles in all participants with metabolic disorders had “good” diagnostic accuracy with area under the receiver operating characteristics curve being 0.72, 0.70 and 0.70 for valine, leucine and isoleucine, respectively.Conclusion. BCAAs concentrations are elevated with higher severity of the cardiovascular disorder and exhibit potential as early independent indicators of coronary artery disease.

Aim . To assess the levels of matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), and miRNA-34a expression in patients with ischemic heart disease (IHD) and obstructive and nonobstructive coronary artery (CA) disease. Material and methods . This cross-sectional observational study included 64 patients with IHD (diagnosis verified by coronary angiography or multislice computed tomography coronary angiography), of which 33 (51.6%) were men aged 64.9±8.1 years. 20 patients had nonobstructive CA disease (stenosis <50%), and 44 had hemodynamically significant stenoses. The control group consisted of 30 healthy volunteers. MMP-1, -9, -13, and -14, miRNA-34a, and VEGF were measured in all patients. Results . The concentration of MMP-1 was significantly higher in patients with ischemia and nonobstructive CA disease (INOCAD) (p=0.016), and the concentration of MMP-9 was the highest in the group with obstructive CA disease (p<0.001). The concentrations of MMP-13 and MMP-14 did not differ significantly between the groups. The highest VEGF concentrations were observed in the INOCAD group (p<0.001). The expression of miRNA-34a significantly differed between the IHD groups with different types of CA disease and controls (p <0.001). Patients with hemodynamically significant stenosis showed moderate relationships between the concentrations of MMP-14 and VEGF (ρ=0.418; p=0.024), as well as between VEGF and miRNA-34a (ρ=0.425; p=0.022). Patients with INOCAD had a significant negative correlation between the concentrations of MMP-13 and VEGF (ρ= –0.659; p=0.003). Correlation analysis showed in all IHD patients a moderate relationship of the concentrations of MMP-1 and MMP-14 with VEGF (ρ=0.449; p=0.002 and p=0.341; p=0.019, respectively). According to ROC analysis, a MMP-9 concentration above 4.83 ng/ml can be a predictor for the presence of hemodynamically significant CA obstruction in IHD patients; a VEGF concentration higher than 27.23 pg/ml suggests the absence of hemodynamically significant CA stenosis. Conclusion . IHD patients with INOCAD had the greatest increase in MMP-1, whereas patients with obstructive CA disease had the highest level of MMP-9. According to our data, concentrations of MMP-9 and VEGF can be used to predict the degree of CA obstruction. The expression of miRNA-34a was significantly higher in IHD patients with INOCAD and CA obstruction than in the control group, which suggested a miRNA-34a contribution to the development and progression of coronary atherosclerosis. In the future, it may be possible to use this miRNA as a diagnostic marker for IHD.

Background — Chronic heart failure with preserved ejection fraction (CHFpEF) develops as a result of many diseases that lead to significant metabolic disorders. Given the heterogeneity of this group of patients, therapeutic options for this syndrome are extremely limited. In this regard, it seems promising to study the metabolomic profile in patients with CHFpEF to identify biomarkers, examine their roles in the pathogenesis of the syndrome, and search for potential targets for targeted therapy. Objective — The study aimed at testing the correlation between the threonine level and the features of the clinical course of CHFpEF. Methods — The study included a total of 154 patients: 82 with CHFpEF, 45 with hypertension and/or coronary artery disease (comparison group), and 27 healthy volunteers (control group). Threonine levels were assessed using high-performance liquid chromatography-mass spectrometry. Results — The threonine concentration was significantly reduced in patients with CHFpEF (1) vs. comparison group (2) and control group (3): p<0.001; p1-3<0.001; p2-3=0.037). A reduction in the threonine level was characteristic for patients with diabetes mellitus vs. patients without it (p=0.029). Conclusion — Given the importance of threonine in energy metabolism and significant changes in its level in various pathophysiological processes, it should be considered as an additional diagnostic and prognostic criterion for CHFpEF. Additional studies are needed to better understand the role of threonine in the pathophysiology of cardiovascular diseases.