Multimarker Approach in Risk Stratification of Patients with Decompensated Heart Failure.

PURPOSE: to study prognostic value of various biomarkers and their combinations in patients who survived decompensation of chronic heart failure. MATERIALS AND METHODS: Patients (n=159) who were hospitalized with diagnosis of heart failure (HF) decompensation were included in a prospective single-center study. Examination on admission and the day of hospital discharge, included measurement of concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), copeptin, soluble suppression of tumorigenicity 2 (sST2), kopetin, neutrophil gelatinase-associated lipocalin (NGAL), and galectin-3. Te combined primary endpoint comprised cardiovascular (CV) death, frst hospitalization because of HF heart failure decompensation, episodes of HF deterioration which required additional i/v diuretics, and CV death with successful resuscitation. RESULTS: During one-year follow-up 56 pts (35.2%) reached the combined primary endpoint. Tere were 78 (49.1%) cardiovascular events. During hospitalization, patients with the decompensation of heart failure experienced a decrease of sST2, NT-proBNP, galectin-3, kopetin, hsTnT and an insignifcant increase of NGAL. ROC analysis identifed signifcant relation between concentrations of NT-proBNP, sST2, copeptin and, to a lesser degree, hsTnT, determined at hospital discharge, and risk of combined primary endpoint during 1-year follow-up: area under the curve (AUC) was 0.733 [95% CI 0.645-0.820], p<0.0001, 0.772 [95% CI 0.688-0.856], p<0.0001, 0.735 [95% CI 0.640-0.830], p<0.0001, and 0.659 [95% CI 0.553-0.764], p=0.005, respectively. Patients who during hospitalization did not achieve cut-off values of NT-proBNP ≤1696 rg/ml, sST2≤37.8 hg/ml, copeptin≤28.31 rmol/L and hsTnT≤28.37 rg/ml, had higher risk of reaching adverse events during 1 year; OR and 95% CI were 2.96 [1.61, 5.42] p<0.0001, 4.31 [2.34, 7.93] p<0.0001, 3.06 [1.59, 5.89] and 2.19 [2.12, 4.27]), respectively. According to Cox regression analysis, risk of the combined primary end point was the highest in patients with 3 or more elevated markers (OR = 6.6 [3.584, 12.158], p<0.0001), average in patients with 2 elevated markers (OR = 1.123 [0.51, 2.48]), p=0.7), and the lowest in patients with no markers increase or increase of only one marker (OR = 0.11 [0.049, 0.241], p<0.0001). In the Kaplan-Mayer survival analysis all three groups were statistically different. In order to identify the most prognostically strong model, a reclassifcation analysis was performed. According to this analysis, the combination of sST2 and NT-proBNP concentrations determined at hospital discharge, exceeded one NT-proBNP (reclassifcation = -8.1%). At the same time, predictive value of only sST2 just insignifcantly less than value of sST2 and NT-proBNP combination (reclassifcation = -1.9%). CONCLUSION: Patients with three and more elevated markers at hospital discharge have high risk of adverse events. Te biggest prognostic value has combination of sST2 and NT-proBNP concentrations. In order to determine the long-term prognosis of a patient with HF decompensation, it is sufcient to measure concentrations of sST2 and NT-proBNP at hospital discharge. Alternatively, it is possible to limit to sST2 only, which is just insignifcantly inferior to the sST2 and NT-proBNP combination. Patients with concentrations of sST2 ≥37.8 hg/ml and NT-proBNP ≥1696 rg/ml at hospital discharge have maximal 1year risk of death due to recurrent HF decompensation.

Clinical significance of serial biomarkers activity determination after acute heart failure decompensation: sST2 NT-proBNP role during long-term follow-up.

AIM: Monitoring of concentrations of modern biomarkers to evaluate the efficacy of long­term treatment of patients after acute decompensated HF (ADHF). MATERIALS AND METHODS: The study included 100 patients with severe decompensated FC II-IV CHF and LV EF <40 % due to IHD, DCMP or AH. At discharge from the hospital, patients were divided into groups of low (NT­proBNP<1400 pg / ml) (control, n=30) and high (NT­proBNP≥1400 pg / ml) risk (n=70). Patients at high risk were randomized to two treatment groups, a group of NT­proBNP monitoring (NPM) (n=35) and a group of standard therapy (n=35). At the end of the study, noncompliant patients were isolated from these two groups into a separate group (n=10). The aim of the treatment was decreasing the NT­proBNP concentration to less than 1000 pg / ml and / or ≥50 % of the baseline level. In addition to the soluble suppression of tumorigenicity 2 (sST2) receptor, concentrations of copeptin, neutrophil gelatinase associated lipocalin (NCAL), galectin 3, and high­sensitivity troponin T were measured at discharge from the hospital (baseline) and at three and 6 months of treatment. RESULTS: The strongest correlations were found between changes in concentrations (Δ%) of NT­proBNP, copeptin, and sST2 and changes in CHF FC, 6­min walk distance, CCS, quality of life, LV EF, and Е / Е' (р<0.001). The incidence of cardiovascular events was directly related with the degree of decrease and / or increase in biomarker concentration. Patients of the NPM group had the lowest risk of adverse clinical outcome upon a decrease in NT­proBNP <988.5 pg / ml at 6 months of treatment or > 50 % of the baseline level at discharge from the hospital. For these patients, the mean Δ% was 60.7±8.5 % for NT­proBNP, 34.03±17.6 % for sST2, and 32.41±8.8 % for copeptin [OR at 95 % CI 0.08 (0.02-0.36), р <0.0001]. A significant increase in the risk for cardiovascular events was observed only at a considerable increase in NT­proBNP >50 % [OR at 95 % CI 3.8 (1.13-13.0), р=0.03], and the highest incidence of cardiovascular events was observed in the group of noncompliant patients (110 %). Besides NT­proBNP, to significantly decrease the risk of cardiovascular events, it was necessary to achieve a decrease in sST2 concentration to less than 30 ng / ml or by more than 24.9 % (Δ%) at the end of followup [ОR (95 % CI: 0.1 (0.02-0.5), р=0.004]. CONCLUSION: Among the modern biomarkers, changes in NT­proBNP, sST2, and copeptin concentrations most accurately reflect changes in the clinical and functional status, quality of life, and EchoCG parameters in HF patients during long­term monitoring. The lowest risk for adverse clinical outcomes was observed in post­decompensation patients with a decrease in NT­proBNP <988.5 pg / ml after 6 months of treatment or ≥50 % of baseline upon discharge from the hospital. The sST2 concentration has to be reduced by more than 24.9 % of baseline and less than 30 ng / ml in the course of long­term treatment after decompensated HF.

[Soluble Suppression of Tumorogenicity 2 Increases Opportunities for Risk Stratification After Acute Heart Failure Decompensation].

PURPOSE: to evaluate the significance of soluble ST2-receptor (sST2) concentrations in patient (pts) risk stratification in with acute decompensated heart failure (ADHF) during long-term follow-up period. METHODS: In the prospective single-center study were included 159 pts with ADHF III-IV FC NYHA. Blood samples to determine NT-proBNP, sST2, hsTnT concentration were collected at the admission and at discharge from the hospital, and after 3, 6 and 12 months of follow-up. The combined primary end point of the trial included cardiovascular (CV) death, hospitalization due to HF, episodes of HF deterioration needed additional i/v diuretics and CV death with successful resuscitation. RESULTS: At admission all pts had elevated biomarker concentrations: NT-proBNP - 3615.5 (1578.0; 6289.3)pg/ml, sST2 - 60,49 (41.95; 92.87) ng/ml, hsTnT - 29.95 (21.85; 49.63) pg/ml; and at discharge: NT-proBNP - 2165.5 (982.7; 4221,2) pg/ml (%=-38,27 (-49.7; -24.34)%, p<0.0001), sST2 - 38.43 (24.67; 63.72) ng/ml (%=-30,13 (-42,07; -17,64)%, p<0,0001), and hsTnT - 28,37(21.29; 46.6) pg/ml. During 1-year follow-up 56 pts (35.2 %) had 78 (49.1%) cardiovascular events. Biomarker concentrations in low risk pts (without CV events) were significantly lower compared with high risk pts (who have CV events). At the discharge NT-proBNP and sST2 concentrations had the most predictive capacity relatively the primary end point during 1-year follow-up: AUC=0.727 (95% CI 0.637-0.816), <0,0001, and AUC=0,768 (95% CI 0.682-0.854), <0.0001, respectively. Maximally sST2 values were predictive for 180 days period of follow-up: AUC=0,809 (95% CI 0.726-0.921; <0,0001). Lack of NT-proBNP and sST2 concentrations decrease below 1696 pg/ml and 37.8 ng/ml respectively were associated with the highest risk of CV events (HR 4.41 [95% CI 1.41-9.624], p<0,0001 and HR 6.755 [95% CI 3.026- 15.082], p<0.0001, respectively). Changes of sST2 concentration during the period of pts hospitalization were also prognostically important, AUC=0.696 (0.596-0.796); p<0.0001. And pts with insufficient degree of sST2 concentrations reduction during the period of hospitalization (% <-28,3%) had the worst short-term and long-term prognosis [HR 3.68 (95% CI 2.05-6.64), p<0.0001]. Values of sST2 at the discharge were the most significant independent predictor of CV events in long-term follow-up (=0.519, p<0.0001). 91,8% of pts without CV events in the study had sST2 and NT-proBNP levels below 37.8 ng/ml and 1696 pg/ml respectively after 3, 6 and 12 months of follow-up. CONCLUSION: The values of soluble ST2-receptor over 37.8 ng/ml and NT-proBNP over 1696 pg/ml at the discharge from the hospital reflects the adverse prognosis in patients with ADHF. Serial determination of sST2 and NT-proBNP concentrations after discharge from the hospital indicates the necessity of reduction the levels of these biomarkers below the cut-off values (<37.8ng/mL and <1696pg/ml respectively) in pts with ADHF in long-term follow-up period.

[Head to Head Comparison of Suppression of Tumorogenicity 2 and Copeptin Significance for Prognosis of Patients After Acute Heart Failure Decompensation].

PURPOSE: To assess the suppression of tumorogenicity 2 (ST2) and copeptin significance for risk stratification of patient (pts) with acute decompensated heart failure (ADHF) during long-term follow-up compared with traditional risk factors. METHODS: We included in a prospective study 159 pts with ADHF. Blood samples to determine copeptin, sST2, NT-proBNP and hsTnT concentration were collected at admission and at discharge from the hospital. Serial determination of biomarker concentration was performed at 3, 6 and 12 months of follow-up. The combined primary end point of the trial included cardiovascular (CV) death, hospitalization due to HF, episodes of HF deterioration requiring additional intravenous diuretics and CV death with successful resuscitation. RESULTS: During 1-year follow-up (295.3±113.2 days) 56 pts (35.2%) had 78 (49.1%) cardiovascular events. Biomarker concentrations in low risk pts (without CV events) were significantly lower compared with high risk pts (with CV events). Discharge copeptin and NT-proBNP values were comparable for pts risk stratification: AUC=0.727 (95% CI 0.637-0.816), р.

[Therapy of High Risk Patients After Decompensation of Heart Failure Under NT-proBNP Control. Main Results].

AIM: to compare efficacy of treatment of high risk patients after acute decompensation (AD) of chronic heart failure (CHF) based on monitoring of NT-proBNP concentration and standard treatment. MATERIAL AND METHODS: Patients (n=100) with class III-IV CHF and left ventricular ejection fraction (LV EF) <40% due to ischemic heart disease (IHD), dilated cardiomyopathy (DCMP), or arterial hypertension (AH) after compensation of HF before discharge were distributed into groups of low (NT-proBNP <1400 picog/ml, n=30) or high (NT-proBNP more or equal 1400 picog/ml, n=70) risk. High risk patients were randomized into 2 treatment groups: NT-proBNP based (group I, n=35) and standard (group II, n=35) therapy. At study closure we formed another group consisting of group I and II participants noncomplaint with study protocol (group NC, n=10). Groups practically did not differ by main clinical functional characteristics. Aim of treatment was lowering of NT-proBNP level below 1000 picog/ml or more or equal 50% from baseline. At discharge median NT-proBNP concentration was 3750.0 (2224.0; 6613.0), 2783.0 (2021.5; 4827.5), and 2162.0 (1684.5; 5750.0) picog/ml in groups I, II, and NC, respectively (=0.315). RESULTS: At study entry all group I and II patients received combination of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, -adrenoblockers, antagonists of mineralocorticoid receptors. After 6 months changes of doses of neuro-hormonal modulators in group I were more pronounced than in group II. NT-proBNP concentration decreased by 53% down to 1585.5 (976,6; 2742,5) picog/ml, =0.001, and by 10.2% in groups I and II, respectively (between group =0.001). In group I compared with II we observed more pronounced improvement of clinical functional indicators, quality of life, and parameters of systolic and diastolic LV function (<0.05), fewer cardiovascular deaths (4 vs. 10, =0.033) and repeat decompensations and rehospitalizations because CHF (4 vs. 14, =0.007). CONCLUSION: Compared with standard therapy long-term NT-proBNP guided treatment of high risk patients significantly significantly decreased rate of CV deaths and repeat decompensations and rehospitalizations because CHF, and more effectively influenced clinical and functional state, quality of life and main echocardiographical parameters of LV systolic and diastolic function.

[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.

[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 [NGAL/lipocalin-2] in patients with chronic heart failure (CHF). It contains description.

[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.