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      ST2 elevation in heart failure, predictive of a high early mortality

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          Abstract

          Background

          Soluble suppression of tumorigenicity-2 (sST2) is a novel biomarker shown to be useful for prognostic assessment in heart failure (HF). However, very limited data exists about its prognostic utility in patients with HF in India.

          Methods

          We studied 150 patients [mean age 67.7 ± 13.3, 93 (62%) males], hospitalized with clinical HF, irrespective of their left ventricular ejection fraction (LVEF). HF was confirmed by N-terminal probrain natriuretic peptide (NT-proBNP) value above 125 ng/L. Primary end point was death or cardiac transplant at 1-year follow-up, with additional telephonic follow-up performed at 2 years. The clinical outcomes were correlated with the sST2 values obtained at the time of initial hospitalization.

          Results

          HF was ischemic in origin in 82.0% patients. The primary outcome occurred in 9.3% patients at the end of 1-year follow-up and in 16.7% patients at the end of 2 years. The patients who had events had significantly higher NT-proBNP and sST2 values, but there was no difference in the clinical characteristics, cause of HF, baseline LVEF, or serum creatinine. The patients with elevated sST2 levels (>35 ng/mL) had substantially higher event rates than those with normal sST2 levels (13.7% vs 0.0% at 1-year, P = 0.005; 22.5% vs 4.2% at 2-years, P = 0.004). On multivariate analysis, sST2 was the strongest predictor of adverse outcomes at both 1-year and 2-year follow-ups.

          Conclusion

          In patients hospitalized for HF, elevated sST2 >35 ng/mL at the time of initial hospitalization was associated with significantly high mortality over a 2-year period. The prognostic value of sST2 was incremental to that of NT-proBNP. These findings suggest that a single elevated sST2 value at the time of hospitalization should alert the physicians about the high risk of adverse outcomes and should help facilitate timely intensification of HF treatment.

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          Most cited references22

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          Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study.

          The aim of this study was to examine the value of measurement of the interleukin-1 receptor family member ST2 in patients with dyspnea. Concentrations of ST2 have been reported to be elevated in patients with heart failure (HF). Five hundred ninety-three dyspneic patients with and without acute destabilized HF presenting to an urban emergency department were evaluated with measurements of ST2 concentrations. Independent predictors of death at 1 year were identified. Concentrations of ST2 were higher among those with acute HF compared with those without (0.50 vs. 0.15 ng/ml; p or =0.20 ng/ml strongly predicted death at 1 year in dyspneic patients as a whole (HR = 5.6, 95% confidence interval [CI] 2.2 to 14.2; p < 0.001) as well as those with acute HF (hazard ratio [HR] = 9.3, 95% CI 1.3 to 17.8; p = 0.03). This risk associated with an elevated ST2 in dyspneic patients with and without HF appeared early and was sustained at 1 year after presentation (log-rank p value <0.001). A multi-marker approach with both ST2 and NT-proBNP levels identified subjects with the highest risk for death. Among dyspneic patients with and without acute HF, ST2 concentrations are strongly predictive of mortality at 1 year and might be useful for prognostication when used alone or together with NT-proBNP.
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            High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure.

            Soluble ST2 reflects activity of an interleukin-33-dependent cardioprotective signaling axis and is a diagnostic and prognostic marker in acute heart failure. The use of ST2 in chronic heart failure has not been well defined. Our objective was to determine whether plasma ST2 levels predict adverse outcomes in chronic heart failure in the context of current approaches. We determined the association between ST2 level and risk of death or transplantation in a multicenter, prospective cohort of 1141 chronic heart failure outpatients. Adjusted Cox models, receiver operating characteristic analyses, and risk reclassification metrics were used to assess the value of ST2 in predicting risk beyond currently used factors. After a median of 2.8 years, 267 patients (23%) died or underwent heart transplantation. Patients in the highest ST2 tertile (ST2 >36.3 ng/mL) had a markedly increased risk of adverse outcomes compared with the lowest tertile (ST2 ≤22.3 ng/mL), with an unadjusted hazard ratio of 3.2 (95% confidence interval [CI], 2.2 to 4.7; P<0.0001) that remained significant after multivariable adjustment (adjusted hazard ratio, 1.9; 95% CI, 1.3 to 2.9; P=0.002). In receiver operating characteristic analyses, the area under the curve for ST2 was 0.75 (95% CI, 0.69 to 0.79), which was similar to N-terminal pro-B-type natriuretic peptide (NT-proBNP) (area under the curve, 0.77; 95% CI, 0.72 to 0.81; P=0.24 versus ST2) but lower than the Seattle Heart Failure Model (area under the curve, 0.81 (95% CI, 0.77 to 0.85; P=0.014 versus ST2). Addition of ST2 and NT-proBNP to the Seattle Heart Failure Model reclassified 14.9% of patients into more appropriate risk categories (P=0.017). ST2 is a potent marker of risk in chronic heart failure and when used in combination with NT-proBNP offers moderate improvement in assessing prognosis beyond clinical risk scores.
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              Incremental value of biomarkers to clinical variables for mortality prediction in acutely decompensated heart failure: the Multinational Observational Cohort on Acute Heart Failure (MOCA) study.

              This study aims to evaluate the incremental value of plasma biomarkers to traditional clinical variables for risk stratification of 30-day and one-year mortality in acutely decompensated heart failure (ADHF).
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                Author and article information

                Contributors
                Journal
                Indian Heart J
                Indian Heart J
                Indian Heart Journal
                Elsevier
                0019-4832
                Nov-Dec 2018
                31 August 2018
                : 70
                : 6
                : 822-827
                Affiliations
                [a ]Centre for Cardiac Sciences, Kokilaben Hospital, Mumbai, India
                [b ]Cardiology, Kokilaben Hospital, Mumbai, India
                [c ]Biochemistry and Immunology, Kokilaben Hospital, Mumbai, India
                [d ]Medanta-The Medicity, Sector 38, Gurgaon, Haryana, 122001, India
                [e ]Veteran Affairs Healthcare System, University of California, San Diego, USA
                [f ]VA Medical Centre, University of California, San Diego, USA
                Author notes
                []Corresponding author. jjdalal@ 123456hotmail.com
                Article
                S0019-4832(18)30173-1
                10.1016/j.ihj.2018.08.019
                6306350
                30580851
                859392fb-a10d-43b8-a9fa-09f0e1608056
                © 2018 Cardiological Society of India. Published by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 18 March 2018
                : 19 August 2018
                Categories
                Clinical and Preventive Cardiology

                st2,heart failure,biomarkers,bnp,nt-probnp,natriuretic peptides
                st2, heart failure, biomarkers, bnp, nt-probnp, natriuretic peptides

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