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.