Cardiometabolic Effects of Empagliflozin in Patients Undergoing Elective Percu-taneous Coronary Intervention for Type 2 Diabetes Mellitus.

Aim      To evaluate cardiometabolic effects of empagliflozin in patients with ischemic heart disease and type 2 diabetes mellitus (DM) following elective percutaneous coronary intervention (PCI).Materials and methods Patients meeting the inclusion/non-inclusion criteria were randomized into two groups of equal number using simple randomization with successively assigned numbers. Group 1 included 37 patients (18 men and 19 women) who gave their consent for the treatment with empagliflozin 10 mg/day in addition to their previous hypoglycemic therapy. The drug administration started one month prior to the elective PCI and continued for the next 11 months (treatment duration, 12 months). Group 2 (comparison group) consisted of age- and DM duration-matched patients (37 patients; 18 men and 19 women) who continued on their hypoglycemic therapy previously prescribed by endocrinologists during the entire study period. Before the study, 36.11 % patients of the empagliflozin group and 27.03 % of the comparison group had unsatisfactory glycemic control as shown by the level of glycated hemoglobin (HbA1c).Results At 6 and 12 months of the study, fasting glycemia and HbA1c were significantly lower in the empagliflozin treatment group. The groups were comparable by the incidence of adverse outcomes: 8 (22.24 %) patients in the empagliflozin group and 10 (27.04 %) patients in the comparison group (р=0.787). The 12-month empagliflozin treatment reduced total cholesterol (C) by 5.56 % (p<0.05), low density lipoprotein (LDL) C by 3.67 % (p<0.05), visceral adipose tissue area (VATA) by 5.83 % (p<0.05), and subcutaneous adipose tissue area (SATA) by 3.54 % (p<0.05).Conclusion      The empagliflozin treatment for 30 days prior to and after elective PCI can enhance the effectiveness of myocardial revascularization due to the demonstrated beneficial cardiometabolic effects.

[Dynamics of Parameters of Transmitral Blood Flow and Markers of Myocardial Fibrosis in Patients with Myocardial Infarction].

Aim      To study possible correlations between echocardiography (EchoCG) indexes and markers of myocardial fibrosis, procollagen I C-terminal propeptide (PICP) and procollagen III N-terminal propeptide (PIIINP) during one year following ST-segment elevation myocardial infarction (STEMI).Material and methods  120 patients with STEMI were evaluated. EchoCG was used to assess dimensions and volumes of heart chambers, left ventricular (LV) systolic function, mean pulmonary arterial pressure (mPAP), and indexes of LV diastolic function (Em, early diastolic lateral mitral annular velocity; e', peak early diastolic septal mitral annular velocity; E / e', ratio of peak early diastolic transmitral inflow velocity and mitral annular velocity  -, Е / А, ratio of peak early and late transmitral inflow velocities; DT, deceleration time of LV early diastolic filling). EchoCG indexes and serum concentrations of PICP and PIIINP were determined at 1 (point 1) and 12 (point 2) days of disease and one year after STEMI (point 3). The sample was divided into two groups: group 1 (n=86; 71.7 %) included patients with a LV ejection fraction (EF) ≥50 % and group 2 (n=34; 28.3 %) consisted of patients with LV EF ≤49 %.Results At one year, the number of patients with signs of diastolic dysfunction increased by 10% in group 1 whereas myocardial systolic dysfunction worsened in both groups. LV EF decreased in 15 (17.4%) patients of group 1 and in 4 (11.8%) patients of group 2. Concentrations of PIIINP were correlated with Em, E / e', mPAP, PICP, e', and LV EF.Conclusion      Direct correlations between PIIINP concentrations and Em, E / e', and mPAP were found in the group with LV EF ≥50 %. In the group with LV EF <50 %, correlations were observed between PICP concentrations, LV EF, and e'. Also, in this group, the increase in PIIINP was statistically more significant. These results indicate continuing formation of myocardial fibrosis in a year following MI, which may underlie progression of chronic heart failure.

[The role of the superoxide dismutase for predicting long-term adverse events in patients with acute coronary syndrome.]

To study the relationship between the blood concentration of superoxide dismutase in at the end of the hospital period of acute coronary syndrome without ST-segment elevation (nonST-ACS) and the development of adverse events in the long-term follow-up period. 415 patients with nonST-ACS are included in the local register study. The follow-up period was 60 months. The blood concentration of superoxide dismutase (SOD) determined in 200 patients on the 10-13th day of hospitalization in addition to clinical procedures. Within five years after discharge in 178 (47 %) patients reported the development of adverse events. Patients with poor outcome were older, had a history of myocardial infarction (PICS), stenoses of extracranial arteries more than 30% and decreased left ventricular ejection fraction (LVEF). There were significant differences in the concentration of SOD10-13 day, which was lower in the patients with development of adverse cardiovascular events (p = 0.0003). Multivariate analysis identified the factors that are most strongly associated with the development of the adverse events during a 5-year follow-up period in patients with nonST-ACS: SOD blood concentration ≤ 175,4 ng / ml (OR-3,85; р=0,0008), myocardial infarction in anamnesis (OR-3,26; р=0,006), LVEF ≤ 52% (OR-2,8; р=0,035). The incidence of adverse cardiovascular events during five years follow-up in patients with nonST-ACS was 47 % of cases. Adverse factors associated with the development of an unfavorable outcome in the long-term period follow are: SOD blood concentration ≤ 175,4 ng / ml, myocardial infarction in anamnesis, LVEF ≤ 52%.

[Relationship Between Blood Serum Galectin and Renal Dysfunction in ST Elevation Myocardial Infarction].

AIM: to assess value for inhospital and 1 year prognosis of unfavorable course of ST-elevation myocardial infarction (STEMI) of blood serum galectin and markers of renal dysfunction (RD). MATERIAL AND METHODS: Standard laboratory and instrumental examination, calculation of glomerular filtration rate using MDRD formula and by cystatin C level, determination of galectin in blood serum were carried out in 128 patients with STEMI. According to GFR by cystatin C level on day 12 of STEMI patients were divided into 2 groups - with normal renal function (GFR more or equal 60 ml/min/1.73 m2, n=47) and with RD (GFR <60 ml/min/1.73 2, n=81). RESULTS AND CONCLUSION: In patients with STEMI presence of RD (lowering of GFR by cystatin C, by blood serum creatinine <60 ml/min/1.73 2, creatinine clearance <60 ml/min), and elevation of galectin concentration >17.8 hg/ml on day 12 of STEMI were independent predictors of unfavorable 1 year prognosis. Elevation of galectin level directly correlated with presence of early postinfarction angina.

[Renal function estimation formulas in predicting long-term cardiovascular outcomes in patients with myocardial infarction concurrent with diabetes mellitus]. / Formuly otsenki funktsii pochek pri prognozirovanii otdalennykh serdechno-sosudistykh iskhodov u bol'nykh infarktom miokarda v sochetanii s sakharnym diabetom.

AIM: To comparatively assess formulas for estimating glomerular filtration rate (GFR) in the prediction of poor outcomes in patients with type 2 diabetes mellitus (DM) within one year after myocardial infarction (MI). MATERIALS AND METHODS: The investigators examined 89 patients with ST-segment elevation myocardial infarction (STEMI) within 24 hours after the onset of clinical symptoms of the disease. All the patients underwent standard laboratory and instrumental tests. GFR was calculated using the Modified of Diet in Renal Diseases (MDRD) formulas in terms of serum creatinine levels, the Hoek equation: GFR [ml/min/1.73 m2] = (80.35/cystatin C [mg/l]) - 4.3 (CKD-EPI), as well as from cystatin C levels, and the creatinine clearance rate was determined using the Cockcroft and Gault formula (ml/min). During a year after STEMI, the investigators recorded cardiovascular events (CVEs), such as death, recurrent MI, progressive angina pectoris, emergency coronary revascularization, and decompensated chronic heart failure (CHF). The examinees were divided into two groups: 1) 70 (78.6%) patients with MI and no DM; 2) 19 (21.3%) patients with MI and DM. RESULTS: Comparative analysis revealed a tendency towards a difference in the detection rate of GFR <60 ml/min/1.73 m2 calculated using the Hoek formula from cystatin C levels: 42.1% in Group 2 and 21.4% in Group 1 (р=0.067). There were no great differences in the GFR estimated using other formulas. Logistic regression analysis was carried out to determine the most sensitive formula for estimating GFR to assess the risk of CVEs in the patients within a year after MI concurrent with and without type 2 DM. A univariate analysis showed that GFR calculations using the CKD-EPI (odds ratio (OR), 13.5; p=0.046) and MDRD (OR, 6.5; р=0.040) formulas and creatinine clearance estimation (OR, 2.4; p=0.025) were most sensitive in selecting MI patients without DM and with poor outcomes. This analysis revealed that GFR estimates using the Hoek formula from cystatin C levels (OR, 6.15; p=0.018) were most sensitive for patients with MI concurrent with type 2 DM. In both models, multivariate analysis included none of the analyzed indicators. CONCLUSION: To estimate cardiovascular risk in the long-term post-infarction period, the CKD-EPI formula in the patients without type 2 DM and the Hoek formula from cystatin C levels were noted to be of the greatest prognostic value in patients with DM.

[The role of chronic kidney disease in assessing the risk of the poor course of hospital ST-segment elevation myocardial infarction].

AIM: To evaluate the prognostic impact of chronic kidney disease (CKD) during hospital stay in patients with ST-segment elevation myocardial infarction (STEMI) and to specify factors showing a negative impact of CKD. SUBJECTS AND METHODS: 954 patients with STEMI were examined. The diagnosis of CKD was verified in 338 (35.4%). In all the patients, glomerular filtration rate (GFR) was calculated using the CKD-EPI formula with regard to serum creatinine levels on admission and before discharge (on days 10--12). In the patients who had undergone X-ray contrast intervention, serum creatinine levels were additionally determined on days 2--3 of this procedure in order to identify contrast-induced nephropathy (CIN). Cardiovascular events were assessed in the hospital period. RESULTS: Endovascular interventions into the coronary vessels were made much more rarely in the patients with CHD; but CIN cases were twice more commonly recorded. Nonfatal cardiovascular events were 1.5 times more frequently observed in the CKD patients in the hospital period. The odds of fatal outcomes in both the total sample of STEMI patients and in those with CKD increased by 3.5 and 3.1 times, respectively, in the over 60 age group and by 7.9 and 5.8 times in the presence of Killip Classes II--IV clinically relevant acute heart failure (AHF). In the total sample, the independent predictors for a fatal outcome were a decreased admission GFR less than 60 ml/min/1.73 m(2), CIN, and Killip II--IV AHF. The hospital nonfatal complications were also associated with a decreased admission GFR less than 60 ml/min/1.73 m(2). CONCLUSION: The independent predictor of a poor hospital period of STEMI, including fatal outcomes, was a decreased admission GFR less than 60 ml/min/1.73 m(2); the presence of CKD was of no independent value.

[Cardio-Ankle Vascular Index and Subclinical Peripheral Atherosclerosis in Patients With Stable Coronary Artery Disease].

AIM: To study relationship between cardio-ankle vascular index (CAVI) and subclinical manifestations of noncoronary atherosclerosis in patients with stable ischemic heart disease (IHD). MATERIAL AND METHOD: We included into this study 511 patients with IHD examined within framework of a register of patients before aorto-coronary bypass surgery. CAVI was determined using VaSera-1000 device. RESULTS: We distinguished 2 groups of patients: (1) with abnormal (≥ 9.0, n = 128) and (2) normal (< 9.0, n = 383) CAVI. Group 1 compared with group 2 had high mean age (p = 0.02), comprised more women (p = 0.0016), hypertensive patients (p = 0.0061), patients with three vessel coronary disease, and patients with stenoses in carotid arteries. Multiple logistic regression analysis revealed independent association between elevated arterial stiffness and age. Elevated arterial stiffness was found in 25% of group 1 patients. Abnormal CAVI was associated with increased intima-media thickness and stenoses of carotid arteries but not with presence of stenoses in arteries of lower extremities.

[A poor outcome prediction scale in ST-segment elevation myocardial infarction patients undergoing emergency percutaneous coronary intervention].

AIM: To make a prediction scale using a set of clinical and laboratory prognostic variables for patients with ST-segment elevation myocardial infarction (STEMI) on their electrocardiograms (ECG) who have undergone percutaneous coronary intervention. SUBJECTS AND METHODS: The study enrolled 154 STEMI patients who had undergone percutaneous coronary angioplasty with stenting of the artery supplying blood to the area of an ischemia. Enzyme immunoassay was used to determine the levels of cytokines and selectins on days 1 and 10. RESULTS: During a year, the authors identified the following independent risk factors of a poor outcome (PO): symptoms of Killip Class III-IV heart failure; a history of smoking; rhythm and conduction disturbances on day 1 of the disease; tumor necrosis factor-alpha levels determined on day 1 of the disease; IL-1alpha and sP-selectin levels measured on day 10. In the made prediction scale, a score was assigned to each independent prognostic variable to estimate the risk of PO. The borderline values of summing the scores, which divided the patients into groups at low, moderate, and high risk for PO, were determined for the practical application of the scale, by using the receiver operating characteristic curve (ROC) analysis. The performance of the model was tested using an independent sample of STEMI patients (n = 50). The probability that the classification of the model was correct amounted to 89.6% (p < 0.0001). CONCLUSION: The made prediction scale allows the patients with STEMI to be allocated to groups at low, moderate, high risks for PO during a year. Evaluation of the prognostic efficiency of the new scale versus the known scales PAMI, CADILLAC, and TIMI ST elevation, by plotting the ROC curve and estimating the area under the latter, demonstrated the high predictive ability of the new scale.

[Risk factors of contrast-induced nephropathy in patients with myocardial infarction].

AIM: To identify predictors of contrast-induced nephropathy (CIN) and evaluate its significance for the hospital prognosis of myocardial infarction with elevated ST segment. MATERIALS AND METHODS: 722 (75.7%) of the total 954 patients underwent X ray examination with the use of contrast material (coronary angiography (CAG) and/or transcutaneous coronary intervention (TCI)) within 24 hr after the appearance of symptoms. In all cases, serum creatinine level was determined and glomerular filtration rate (GFR) calculated by the MDRD formula at admission, 2-3 days after CAG/TCI, and 10-14 days after hospitalization. CIN was defined as a more than 25% (44 mcmnol/l) rise in the creatinine level compared with the initial one within 48-72 hr after intravascular administration of contrast material in the absence of an alternative cause. The endpoints (adverse cardiovascular effects) were evaluated at the hospital stage of the study. RESULTS: Significantly more patients with CIN (n=52; 7.2%) had the history ofdiabetes mellitus (DM) and chronic renal disease (CRD), clinically manifest Killip class II-IV acute cardiac failure (ACF), and reduced left ventricular ejection fraction (LVEF) compared with the patients having normal renal function. The risk of RAEF in the presence of CIN increased by 2.5 times (95% CI 1.26-5.05), that of MI by 5.4% (95% CI 2.69-10.64), life-threatening and other complications by 4.1% (95% CI 1.99-8.29) and 5.1% (95% CI times 2.85-9.17) times respectively. The presence of Killip class II-IV ACF increased the risk of CIN and DM by afactor of 2.2. CONCLUSION: CIN was diagnosed in 7.2% of the patients with myocardial infarction and elevated ST segment; it is associated with the history of DM, CRD, pronounced Killip class II-IV ACF and decreased LVEF DM and clinically manifest ACF were independent predictors of CIN in patients with myocardial infarction and elevated ST segment.

[Prognostic value of various markers of inflammation in ST-elevation myocardial infarction].

We measured levels of several parameters of immune inflammation (interleukins [IL] 1, 6, 8, 10, 12, tumor necrosis factor [TNF], serum neopterin, C-reactive protein) on days 10-14 after onset of ST segment elevation myocardial infarction (MI) and related them to results of 12 months follow up. Elevated titers of IL-12 and neopterin were significantly associated with unfavorable events (repetitive MI, progression of angina, stroke, decompensation of chronic heart failure) (=0.001 and =0.003, respectively). After adjustment for initial severity of MI only IL-12 retained its prognostic value (=0.05). Regression analysis identified IL-12 level >108.7 g/ml and TIMI score > 3 as independent predictors of combined end point formation. Prognostic value of IL-12 level was significant both among patients with TIMI scores <3 and more or equal 4.

[Polymorphism at codon 117 of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene]. / Polimorfizm v kodone 117 gena granulotsit-makrofag-koloniestimuliruiushchego faktora (GM-KSF).

A T-to-C substitution, replacing a hydrophobic isoleucine residue with a hydrophilic threonine residue in position 100 of a mature protein molecule, was found at codon 117 of the GM-CSF gene. The mutation frequencies were estimated in 51 DNA samples from healthy adult donors and also in 20 samples from patients with different neoplastic myeloid disorders. Almost equal substitution frequencies in patients and normal individuals were observed, suggesting that the defect was not associated with leukemia. Additionally the GM-CSF gene intron 1 sequence was refined.