[The role of markers of organ damage in patients with chronic heart failure].

This review is devoted to the studies of the role of modern markers of myocardial and renal damage (high sensitivity troponin T [hsTnT] and urinary neutrophil gelatinase-associated lipocain [NGA/lipocalin-2] in patients with chronic heart failure (CHF). It contains description of nature, mechanism of synthesis, and release of hsTnT and NGAL, problems of variability of determination of these biomarkers, consideration of causes of elevation of their activity in CHF. Both hsTnT and NGAL have high diagnostic and prognostic significance. Determination of these biomarkers in combination with natriuretic peptides gives complimentary information for more accurate stratification of risk of development of possible complications. Measurement of activity of hsTnT and NGAL (lipocalin-2) will make it easier for a physician to solve the problem of optimization of therapy and management of a concrete patient.

[Assessment of clinical-instrumental, morphological data and expression of coxsackie adenovirus receptor in patients with inflammatory cardiac pathology].

In 22 patients with heart failure and/or ventricular arrhythmias presumably of inflammatory etiology the results of clinical and instrumental investigation were analyzed and compared to the endomyocardial biopsy data. In the subgroup of patients with left bundle branch block (LBBB) we revealed features indicative of lesser contribution of inflammatory destruction in pathogenesis of cardiomyopathy. The only virus, detected in biopsy samples, was parvovirus B19. Its persistence in myocardium was not related to activity of inflammation and severity of clinical course. Increased expression of Coxsackie adenovirus receptor (CAR) was found in 20 patients. It was not related to inflammatory cells infiltration and virus persistence in myocardium. Patients with most prominent CAR expression were characteried by right heart dilatation, more severe heart failure and absence of LBBB. Enhancement of CAR expression could reflect the attempt of organism to repair intercellular communications between cardiomyocites and to protect cells from the products of necrotic lysis during long standing inflammation.

[Diagnostic capabilities of cardiac magnetic resonance imaging in patients with inflammatory cardiomyopathy: comparison of its results with endomyocardial biopsy data and clinical picture].

AIM: To evaluate the diagnostic capabilities of cardiac magnetic resonance imaging (MRI) in patients with inflammatory cardiomyopathy (ICMP) and to compare its results with endomyocardial biopsy (EMB) data and clinical and laboratory parameters. SUBJECTS AND METHODS: Cardiac MRI was performed using the "Lake Louise Criteria" in 51 patients with ICMP and a 4.1 +/- 3.4-year history of chronic heart failure (CHF). EMB was carried out in 25 patients. Their clinical state was evaluated by the results of a 6-minute walk test and by a clinical assessment scale; N-terminal pro-brain natriuretic peptide levels were estimated. All the patients received the recommended therapy for CHF. RESULTS: Myocardial areas of delayed enhancement were found in 20 (39%) patients. Myocardial edema or early contrast enhancement was not recorded in any case. An immunohistological study revealed myocardial inflammation in 12 (48%) patients. Six patients with chronic myocarditis and 4 patients without myocarditis had delayed-phase contrast enhancement areas. There was a statistically significant correlation of the contrast-enhanced myocardial volume with the frequency of single and paired ventricular premature beats (r = 0.66; p = 0.002 and r = 0.54; p = 0.01). CONCLUSION; The patients with delayed enhancement are at high risk of ventricular tachycardia. The severity of CHF is uncorrelated with the contrast-enhanced myocardial volume. Delayed enhancement is unrelated to the activity of myocardial inflammation, as evidenced by the immunohistological study.

[Treatment of patients with chronic heart failure based on monitoring of concentrations of natriuretic peptides--to what extent it is justified in clinical practice?].

The review is devoted to consideration of novel pathways of treatment of patients with chronic heart failure (CHF) in particular of the high risk group. All main studies of the problem of treatment of patients with CHF based on monitoring of concentration of natriuretic peptides (MCNUP) BNP or NT-proBNP have been analyzed. The use of MCNUP with the aim of optimizing treatment of patients with CHF is completely justified biologically. Nevertheless results of available studies gave no 100% evidence of efficacy of such therapy mostly because of insufficient statistical power of these studies to obtain such a proof. In most of positive studies effect of MCNUP controlled therapy was assessed with the use of composite end points and main contribution in achievement of success was made not by effect on mortality but on stabilization of clinical state with lowering of number of hospitalizations due to CHF. This fact was confirmed in most of the protocols--both positive and neutral--in patients younger than 75 years with systolic left ventricular dysfunction. Taking into consideration pronounced effect of MCNUP controlled therapy on development of repeat decompensations and CHF related hospitalizations this variant of therapy can be justified especially in high risk patients requiring intensified control and optimization of therapy after discharge from hospital.

[Inflammatory cardiomyopathy: state-of-the-art].

Cardiomyopathy (CMP) is a major cause of early disability and death in young cardiac patients, remaining at the same time a little studied problem. The generally accepted term "dilated cardiomyopathy" is only a portrayal of morphological signs. As of now, the foreign literature most commonly uses the term "inflammatory cardiomyopathy" to denote CMP caused by viral and/or bacterial agents. Owing to the wide use of novel laboratory and instrumental diagnostic techniques, namely: molecular genetic and immunohistochemical studies and endomyocardial biopsy, there has been a possibility to conduct a more accurate and fuller study of inflammatory CMP. Despite the fact that the problems in nosology, classification, choice of the optimal diagnostic methods and management tactics for these patients.

[Influence of chronic cardiac failure severity on the course of comorbid type 2 diabetes mellitus].

AIM: To assess relations between severity of chronic cardiac failure (CCF) and a course of comorbid type 2 diabetes mellitus (DM). MATERIAL AND METHODS: Time course changes of cerebral natriuretic peptide (CNUP) were used as a criterion of CCF severity in 81 patients with mild and moderate CCF (NYHA functional class II-III), left ventricular ejection fraction (LVEF) < 45% and type 2 DM. Of them, two groups of 19 patients each were compiled--with the highest and lowest CNUP levels. Also, patients with a rising CNUP level and CCF FC (n = 5) and those with decreasing CNUP and FC improvement (n = 33) were analysed. The following parameters were studied at baseline and 6 months later: clinicofunctional status, glomerular filtration rate (GFR), neurohormonal profile (CNUP), noradrenalin and angiotensin II, the level of HbA1c, baseline and postprandial plasma glucose, serum insulin and C-peptide. RESULTS: Insignificant changes in glycemia in low C-peptide were found in groups with mild CCF. In patients with high CNUP and CCF FC there was a positive correlation between high CNUP, noradrenalin and fasting glucose. With growing severity of CCF clinicofunctional status of the patients was deteriorating while levels of noradrenalin and angiotensin II tended to rise. CONCLUSION: Moderate decompensation of CCF had no effect on the course of associated DM. More severe and long-term decompensation may be accompanied with noticeable changes in glycemia.

[Effect of strict glycemic control on clinical state and course of the disease in patients with chronic heart failure and type II diabetes mellitus. Results of the REMBO "rational effective multicomponent therapy in the struggle against diabetes mellitus in patients with congestive heart failure" study].

With the aim to investigate influence of glycemic control on clinical state and course of disease, renal function, and neurohormonal profile of patients with chronic heart failure (CHF) and type 2 diabetes mellitus (DM) we studied 81 patients with NYHA functional class (FC) II - III CHF, left ventricular ejection fraction (LVEF) 45% and type 2 DM. As a result of randomization 2 groups were formed - active with achievement of target levels of glycemia (n=41) and usual treatment (n=40). Retrospective analysis in dependence of efficacy of sugar lowering therapy was also conducted. Group 1 (n=18) comprised patients with achieved 1% lowering of glycated hemoglobin (HbA1 ), group 2 (n=26) - patients with bA1c lowering < 1%, group 3 (n=31) - patients with increase of HbA1 . Total duration of the investigation for the first analysis was 12, for the second - 6 months. Control examination was carried out at baseline, after 6 and 12 months of investigation and included assessment of clinico-functional status, glomerular filtration rate, neurohormonal profile (brain natriuretic peptide, noradrenalin, and angiotensin II). The state of carbohydrate metabolism was assessed with the help of determination of the level of HbA1c and oral glucose tolerance test. Absence of dynamics of glycemia in active and nonactive groups, in the active group improvement of clinico-functional status, quality of life, and parameters of remodeling was noted. Complementary retrospective analysis revealed improvement of functional status, renal function, and lowering of RAAS activity at 1% lowering of HbA1 and achievement of its target values. With this it was shown that betterment of functional possibilities ensued at lowering of HbA1c level not less than by 0.8%. Thus necessity and efficacy of strict glycemic control of DM in patients with CHF was proved.

[Efficacy and safety of the use of metformin in patients with chronic heart failure and type 2 diabetes mellitus. results of the study "rational effective mulicomponent therapy in the battle against diabetes mellitus in patients with chronic heart failure"].

Aim of the investigation was to study safety of therapy with metformin and its effect on clinical, hemodynamic, functional and neurohumoral status in patients with chronic heart failure and type 2 diabetes mellitus DM). Eighty one patients with light and moderate NYHA functional class (FC) II-III CHF, left ventricular ejection fraction < 45%, and DM were examined. As a result of randomization 2 groups were formed: with active (n=41) and usual (n=40) treatment. In active group with achievement of target levels of glycemia 24 (59%) patients were on oral hypoglicemic drags, 17 (41) patients received. All patients were on basal therapy of CHF. Initially efficacy and safety of metformin was investigated in a cohort of active treatment (jn metformin n=29, control n=12), including patients who were prescribed metformin not for the whole period. In addition in active group analysis was carried out among patients, who continually were treated with metformin for 12 months (n=30) in comparison with patients never treated with metformin (n=8). Total duration of the period of treatment and supervision was 12 months. Control examination was conducted before randomization, after 6 months of treatment, at the end of the study and included assessment of clunico-functional status of patients, renal function (GFR), neurohumoral profile (MNUP, NA, AII). The state of carbohydrate metabolism was assessed with the help of determination of HBA1C level and test with nutritional load given as of common breakfast -- 2-3 in the course of which fasting and postprandial level (in 2 hours after breakfast) of glucose (GLC), and fasting insulin and C-peptide. Overall safety of metformin was confirmed -- throughout whole period of follow up with different variants of comparative analysis no cases of lactic acidosis were revealed. Practical lack of positive influence of metformin on glycemia at its initially not high level was accompanied with improvement of FC CHF, parameters of central hemodynamics, augmentation of functional capacities of patients, improvement of quality of life, lowering of number of decompensations of CHF and diminishment of degree of activation of SAS. It can be suggested that this dynamics is conditioned by the presence of cardioprotective properties in metformin what allows to recommend its application in patients with CHF and type 2 DM.

[Clinical, hemodynamic and neurohumoral effects of long-term therapy of patients with severe chronic heart failure with beta-adrenoblocker bisoprolol]. / Kliniko-gemodinamicheskie i neirogormonal'nye éffekty dlitel'noi terapii beta-adrenoblokatorom bisoprololom bol'nykh s tiazheloi khronicheskoi serdechnoi nedostatochnost'iu.

UNLABELLED: The use of beta-adrenoblockers in conjunction with angiotensin converting enzyme inhibitors improves quality of life and prognosis of patients with chronic heart failure. However basic mechanisms of these positive effects in severe heart failure remain to be elucidated. METHODS: Patients (n=54) with NYHA class III-IV heart failure and left ventricular ejection fraction < or =35% were randomized either to treatment with bisoprolol (1.25-10 mg/day) (n=30) or in control group (n=24) and were followed up for 12 months. RESULTS: The use of bisoprolol was associated with significant improvement of heart failure functional class, lowering of heart rate (by 14%, p<0.01), elevation of systolic blood pressure (by 7.2+/-12.3 mm Hg, p<0.01) and increase of walking distance (by 30.1+/-29.0 m, p<0.01). No significant changes of these parameters occurred in control group. After 12 months increases of left ventricular end diastolic and end systolic volumes (by 85+/-69.2 and 71+/-51.5 ml, respectively, p<0.001) and of ejection fraction (by 5.7+/-7.3%, p<0.01) took place in bisoprolol treated patients. These changes were significantly (p<0.001) higher than those in control group. After 6 months of treatment with bisoprolol noradrenaline concentration fell from 533 to 402 pg/ml (p<0.05) while in controls it rose from 369 to 474 pg/ml, p<0.01). Decreases of plasma renin activity (from 1.2 to 0.42 ng/ml/h), plasma concentrations of angiotensin II (from 17.1 to 13.1 pg/ml) and aldosterone (from 173 to 148 pg/ml, p<0.05) were also observed in bisoprolol group. No substantial dynamics of activity of main components of renin angiotensin system took place in controls. There were no significant changes of atrial natriuretic peptide in both groups. Significant positive dynamics of parameters of heart rate variability was registered only in bisoprolol group: SDNN increased by 25% (p<0.05), high frequency spectrum by 106% (p=0.03), LF/HF ratio from 2.18+/-1.41 to 1.82+/-0.7. CONCLUSION: Long term use of bisoprolol was associated with improved clinical and hemodynamic status, increased systolic BP, blocked processes of pathological left ventricular remodeling, lowered activity of not only sympathetic-adrenal but also of main components of renin-angiotensin system and improved heart rate variability.