The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. The use of metabolomics approaches seems promising in speeding up and simplifying the diagnostic process in HFpEF patients, which can lead to earlier treatment initiation and better improvement of patient condition. The aim of this study was to develop a diagnostic panel of metabolites (metabolomic biomarkers) for the detection and diagnosis of HF with preserved ejection fraction. The study included 76 participants with hypertension, 36 of whom were diagnosed with HFpEF. The blood plasma metabolomic profile, including 72 metabolites, was detected using high-performance liquid chromatography combined with mass spectrometry. There were 18 statistically significant differences in concentrations of metabolites and 3 differences in their ratios between HFpEF and hypertension groups. The prognostic model for detecting the possibility of HFpEF included seven metabolites and two ratios: hexadecenoylcarnitine, arginine, trimethylamine-N-oxide, asymmetric dimethylarginine (ADMA), arginine/ADMA ratio, kynurenine, kynurenine/tryptophan, neopterin, and anthranilic acid. The area under the ROC curve was 0.981 ± 0.017. The resulting model was statistically significant (p < 0.001). The metabolomic panel could be considered as an addition to the present HFpEF laboratory diagnostic criteria for blood plasma analysis in clinical practice.

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. 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.

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.

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p<0,05) and Tyr (r=-0,583, p<0,05), as well as the level of Phe with total cholesterol (r=-0,461, p<0,05) was found in the group without CVD. In the hypertension group, only a weak positive correlation was found between very low-density lipoproteins and AAA levels (Phe r=0,326 and Tyr r=0,365, p<0,05), while in patients with CAD, the level of Phe and Tyr was negative correlated with high-density lipoprotein (r=-0,378 and r=-0,543, respectively, p<0,05), and the level of Tyr with LDL (r=0,349, p<0,05). When isolating the group with proven atherosclerosis of peripheral and/or coronary arteries, a statistically significant difference was revealed between the group of patients with CVD and clinical and instrumental signs of atherosclerosis and the group of patients with CVD without proven atherosclerosis in Phe level (p=0,019).Conclusion. Concentrations of AAA were higher in patients with CVD, comparing with the control group. At the same time, an increase of the Phe level was associated with the presence of peripheral or coronary atherosclerosis. The revealed correlations of AAA with EchoCG parameters and lipid spectrum parameters require further study to understand the involvement of AAA in pathogenesis of CVD and its potential role as treatment target.