In structure of mortality, the leading cause of death of adults in economically developed countries is heart disease with heart failure. Early risk stratification before clinical manifestation of decompensated heart failure is relevant and extremely important task. Aim. The study was aimed at searching for new diagnostic biomarkers and predictors of high risk of adverse cardiovascular events and mortality in patients with decompensated heart failure. A total of 206 patients, enrolled in the study, were assigned into 3 groups: group 1 comprised 94 patients with postmyocardial infarction or ischemic remodeling where the prognostic importance of growth factors of VEGf, PDGF-AB, and FGF basic was studied; the diagnostic importance of TIMP-1 was studied in 52 patients with HF NYHA classes II- IV (group 2); and the predictive value of Lp-FLA2 was analyzed in 60 patients with diabetes mellitus type 2 associated with HF NYHA class II (group 3). Receiver operating characteristic (ROC) curves used for assessing the accuracy of predictions revealed high positive predictive values for growth factors VEGF (the area under a curve 0.71+0.05; r=0.000) and FGF basic (0.71+0.05; r=0.000), for PDGF-AB (0.66+0.06; r=0.009). Plasma level of TIMP-1>485.7 ng/mL was found to be an independent, highly sensitive prognostic factor of progression of HF and mortality (specificity of 100%; sensitivity of 80.4%). We found high correlation (r=0.66; p=0.000) between concentration of Lp-FLA2 and a frequency of a stenosis of coronary arteries in patients with type 2 diabetes mellitus (cutoff level of Lp-FLA2 983 ng/mL, sensitivity of 80%; specificity of 100%). Prognostic value of TIMP-1 as an independent marker of risk for progressing of HF and mortality is great and it should be used more widely in cardiology practice. Our study suggests that the levels of growth factors and Lp-FLA2 can be used as candidate markers associated with ischemic dysfunction of the heart, atherosclerosis of coronary arteries, and metabolic disorders. Larger studies are required to verify these findings.

Opioid peptides belong to the new actively studied class of the pharmacological agents showed to possess a stress-limiting and possibly cardioprotective effects modulating the activity of μ- and δ-opioid receptors. Thereby, studying the prospects for clinical application of opioid receptors is extremely important. Aim: to study the role of opioid receptors agonist dalargin and opioid receptor antagonist naloxone in heart rhythm disorders and in altered repolarization phase of the ventricles in the model of experimental cerebral fat embolism including hypothalamic damage in rabbits. A total of 48 chinchilla rabbits were used as experimental models for the rhythm disorders occurred as a complication of cerebral fat embolism; the antiarrhytmic and cardioprotective effects of opioid receptors (OR) agonists dalargin and opioid receptor antagonist naloxone were examined. Data showed that experimental cerebral fat embolism caused various types of arrhytmias with different morphology and severity, myocardial infarction-like ECG changes, and WPW-like ECG changes. Both classes of drugs increased survival of animals with cerebral fat embolism. Naloxone surpassed dalargin in reducing the frequency of ventricular fibrillation and WPW activity. Results of our research show that experimental cerebral fat embolism is associated with hypothalamus damage and high risk of development of fatal arrhythmias. Administration of opioid receptors agonist dalargin or opioid receptors antagonist naloxone provided the stress-limiting, antiarrhytmic, and probably cardioprotective effects, significantly improving survival of animals.

It has been reported that the increased expression of natural inhibitors of the matrix metalloproteinases is associated with the high risk of mortality and heart failure progression. The aim of the study was to estimate the diagnostic value of tissue inhibitor of metalloproteinase-1 (TIMP-1) for the diagnosis of heart failure in patients with myocardial ischemia and/or post-myocardial infarction remodeling. A total of 52 patients with heart failure NYHA classes II, III, and IV were enrolled in the study. Diagnostic value and prognosis for adverse cardiovascular events were analyzed in the prospective 6-month observation. The patients were divided into three groups according to heart failure severity: group 1 included patients with NYHA class II (n=18) with preserved left ventricular (LV) ejection fraction (EF) (>45%), group 2 included patients with NYHA class III (n=23) with decreased LV EF, and group 3 included patients with the most severe NYHA class IV chronic heart failure (n=11) and LV EF of <32.5%. The age of the patients was 60.6+0.92 years. The TIMP-1 level in blood was determined by hard phase immunoenzyme analysis. All-cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), need for revascularization, need for hospitalization, and definite progression of heart failure were the clinical endpoints with 6-month follow-up. The TIMP-1 level in patients of group 1 ranged from 181 to 375.9 ng/ml (Me=278.45 ng/ml); patients in group 2 had TIMP-1 levels ranging from 376.6 to 897.8 ng/ml (Me=637.2 ng/ml), and the levels of TIMP in patients of group 3 were significantly higher, ranging from 903.6 to 1687.9 ng/ml (Me=1295.8 ng/ml). Two patients with end-stage heart failure from group 2 and group 3 died during the study; their TIMP-1 levels were 1289.9 and 1687 ng/ml, respectively. In patients with ischemic heart disease, heart failure, and postmyocardial infarction remodeling, TIMP-1 can be considered a new independent predictor of ischemic myocardial dysfunction and LV fibrosis.

Angiotensin-converting enzyme (ACE) inhibitors are recommended as the first-line drugs for the prevention of cardiovascular diseases. There is evidence that new class of angiotensin receptor blockers (ARBs) have at least the same efficacy for the prevention of cardiovascular disease as ACE inhibitors in patients with heart failure due to the attenuation of excessive renin-angiotensin system activity. Data on efficacy of aldosterone synthesis blockage for the prevention of chronic heart failure have been accumulated in large randomized clinical trials. The aim of the study was to investigate efficacy of combination blockage of angiotensin II receptor, type 1 (AT 1 receptors) and aldosterone receptors for correction of arterial stiffness and neurohormonal abnormalities in chronic heart failure. We analyzed long-term (6-month) efficacy and safety of combination therapy with ARB (valsakor) and aldosterone receptor blocker (spironolactone) in 34 patients (age 62.3±3.9 years) mainly with NYHA class III heart failure and reduced ejection fraction (EF) - 33%. Quantification of left ventricular stiffness and ventricular-arterial coupling was performed by using three-dimensional echocardiography. We tested blood NT-proBNP level by BNP-assay and serum aldosterone by the direct radioimmunoassay. During 6 months of the study, all patients received pathogenetic therapy. Data showed favorable clinical dynamics in general condition of patients, regression of left ventricular remodeling, improvement in indexes of arterial stiffness and cardiac inotropic function resulting in reliable increase in EF (р=0.003). Serum levels of neuromediators, NT-proBNP and aldosterone, showed clear tendency to decrease compared with the initial values. Therefore, the long-term pathogenetic combination therapy of NYHA class III heart failure with valsakor and spironolactone is safe and efficacious. It results in the regression of heart failure, moderate reversal of left ventricular remodeling and increased arterial stiffness, and improvement of the prognosis for the disease.