Research Article| Volume 27, ISSUE 11, P1240-1250, November 2021

Comparison of Soluble ST2, Pentraxin-3, Galectin-3, and High-Sensitivity Troponin T of Cardiovascular Outcomes in Patients With Acute Decompensated Heart Failure



      Data regarding a direct comparison of soluble suppression of tumorigenesis-2 (sST2), pentraxin 3 (PTX3), galectin-3 (Gal-3), and high-sensitivity troponin T of cardiovascular outcome in patients with heart failure (HF) are lacking.

      Methods and Results

      A total of 616 hospitalized patients with HF were evaluated prospectively. Biomarker data were obtained in the stable predischarge condition. sST2 levels were associated with age, sex, body mass index, inferior vena cava diameter, B-type natriuretic peptide (BNP), PTX3, C-reactive protein, and Gal-3 levels. During follow-up, 174 (28.4%) primary composite end points occurred, including 58 cardiovascular deaths and 116 HF rehospitalizations. sST2 predicted the end point after adjustment for 13 clinical variables (hazard ratio 1.422; 95% confidence interval [CI] 1.064 to 1.895, P = .018). The association between sST2 and the end point was no longer statistically significant after adjustment for BNP (P = .227), except in the subgroup of patients with preserved ejection fraction (hazard ratio 1.925, 95% CI 1.102–3.378, P = .021). Gal-3 and high-sensitivity troponin T predicted the risk for the end point after adjustment for age and sex, but were not significant after adjustment for clinical variables. The prognostic value of PTX3 was not observed (age and sex adjusted, P = .066).


      This study did not show significant additional value of biomarkers to BNP for risk stratification, except sST2 in patients with preserved ejection fraction.

      Key Words

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        • Bettencourt P
        • Azevedo A
        • Pimenta J
        • Frioes F
        • Ferreira S
        • Ferreira A.
        N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients.
        Circulation. 2004; 110: 2168-2174
        • Doust JA
        • Pietrzak E
        • Dobson A
        • Glasziou P.
        How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review.
        BMJ. 2005; 330: 625
        • van Kimmenade RR
        • Januzzi Jr, JL
        • Ellinor PT
        • Sharma UC
        • Bakker JA
        • Low AF
        • et al.
        Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure.
        J Am Coll Cardiol. 2006; 48: 1217-1224
        • Yancy CW
        • Jessup M
        • Bozkurt B
        • Butler J
        • Casey Jr., DE
        • Drazner MH
        • American College of Cardiology Foundation and American Heart Association Task Force on Practice Guidelines
        2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2013; 62: e147-e239
        • Troughton RW
        • Frampton CM
        • Brunner-La Rocca HP
        • Pfisterer M
        • Eurlings LW
        • Erntell H
        • et al.
        Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis.
        Eur Heart J. 2014; 35: 1559-1567
        • Januzzi Jr, JL
        • Filippatos G
        • Nieminen M
        • Gheorghiade M
        Troponin elevation in patients with heart failure: on behalf of the third Universal Definition of Myocardial Infarction Global Task Force: Heart Failure Section.
        Eur Heart J. 2012; 33: 2265-2271
        • Gravning J
        • Askevold ET
        • Nymo SH
        • Ueland T
        • Wikstrand J
        • McMurray JJ
        • et al.
        Prognostic effect of high-sensitive troponin T assessment in elderly patients with chronic heart failure: results from the CORONA trial.
        Circ Heart Fail. 2014; 7: 96-103
        • Aimo A
        • Januzzi Jr., JL
        • Vergaro G
        • Ripoli A
        • Latini R
        • Masson S
        • et al.
        Prognostic value of high-sensitivity troponin t in chronic heart failure: an individual patient data meta-analysis.
        Circulation. 2018; 137: 286-297
        • Weinberg EO
        • Shimpo M
        • Hurwitz S
        • Tominaga S
        • Rouleau JL
        • Lee RT.
        Identification of serum soluble ST2 receptor as a novel heart failure biomarker.
        Circulation. 2003; 107: 721-726
        • Broch K
        • Ueland T
        • Nymo SH
        • Kjekshus J
        • Hulthe J
        • Muntendam P
        • et al.
        Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology.
        Eur J Heart Fail. 2012; 14: 268-277
        • van Vark LC
        • Lesman-Leegte I
        • Baart SJ
        • Postmus D
        • Pinto YM
        • Orsel JG
        • et al.
        Prognostic value of serial ST2 measurements in patients with acute heart failure.
        J Am Coll Cardiol. 2017; 70: 2378-2388
        • Emdin M
        • Aimo A
        • Vergaro G
        • Bayes-Genis A
        • Lupon J
        • Latini R
        • et al.
        sST2 predicts outcome in chronic heart failure beyond NT-proBNP and high-sensitivity troponin T.
        J Am Coll Cardiol. 2018; 72: 2309-2320
        • O'Meara E
        • Prescott MF
        • Claggett B
        • Rouleau JL
        • Chiang LM
        • Solomon SD
        • et al.
        Independent prognostic value of serum soluble ST2 measurements in patients with heart failure and a reduced ejection fraction in the PARADIGM-HF Trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure).
        Circ Heart Fail. 2018; 11e004446
        • Aimo A
        • Vergaro G
        • Ripoli A
        • Bayes-Genis A
        • Pascual Figal DA
        • de Boer RA
        • et al.
        Meta-analysis of soluble suppression of tumorigenicity-2 and prognosis in acute heart failure.
        JACC Heart Fail. 2017; 5: 287-296
        • Kotooka N
        • Inoue T
        • Aoki S
        • Anan M
        • Komoda H
        • Node K.
        Prognostic value of pentraxin 3 in patients with chronic heart failure.
        Int J Cardiol. 2008; 130: 19-22
        • Suzuki S
        • Takeishi Y
        • Niizeki T
        • Koyama Y
        • Kitahara T
        • Sasaki T
        • Sagara M
        • et al.
        Pentraxin 3, a new marker for vascular inflammation, predicts adverse clinical outcomes in patients with heart failure.
        Am Heart J. 2008; 155: 75-81
        • Latini R
        • Gullestad L
        • Masson S
        • Nymo SH
        • Ueland T
        • Cuccovillo I
        • Investigators of the Controlled Rosuvastatin Multinational Trial in Heart Failure and trials GI-HF
        Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials.
        Eur J Heart Fail. 2012; 14: 992-999
        • Matsubara J
        • Sugiyama S
        • Nozaki T
        • Akiyama E
        • Matsuzawa Y
        • Kurokawa H
        • et al.
        Incremental prognostic significance of the elevated levels of pentraxin 3 in patients with heart failure with normal left ventricular ejection fraction.
        J Am Heart Assoc. 2014; 3e000928
        • Matsubara J
        • Sugiyama S
        • Nozaki T
        • Sugamura K
        • Konishi M
        • Ohba K
        • et al.
        Pentraxin 3 is a new inflammatory marker correlated with left ventricular diastolic dysfunction and heart failure with normal ejection fraction.
        J Am Coll Cardiol. 2011; 57: 861-869
        • Lok DJ
        • Van Der Meer P
        • de la Porte PW
        • Lipsic E
        • Van Wijngaarden J
        • Hillege HL
        • et al.
        Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study.
        Clin Res Cardiol. 2010; 99: 323-328
        • Shah RV
        • Chen-Tournoux AA
        • Picard MH
        • van Kimmenade RR
        • Januzzi JL.
        Galectin-3, cardiac structure and function, and long-term mortality in patients with acutely decompensated heart failure.
        Eur J Heart Fail. 2010; 12: 826-832
        • Ho JE
        • Liu C
        • Lyass A
        • Courchesne P
        • Pencina MJ
        • Vasan RS
        • Larson MG
        • et al.
        Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community.
        J Am Coll Cardiol. 2012; 60: 1249-1256
        • Sharma UC
        • Pokharel S
        • van Brakel TJ
        • van Berlo JH
        • Cleutjens JP
        • Schroen B
        • et al.
        Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction.
        Circulation. 2004; 110: 3121-3128
        • Bottazzi B
        • Bastone A
        • Doni A
        • Garlanda C
        • Valentino S
        • Deban L
        • et al.
        The long pentraxin PTX3 as a link among innate immunity, inflammation, and female fertility.
        J Leukoc Biol. 2006; 79: 909-912
        • Sanada S
        • Hakuno D
        • Higgins LJ
        • Schreiter ER
        • McKenzie AN
        • Lee RT.
        IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system.
        J Clin Invest. 2007; 117: 1538-1549
        • Ho KK
        • Anderson KM
        • Kannel WB
        • Grossman W
        • Levy D
        Survival after the onset of congestive heart failure in Framingham Heart Study subjects.
        Circulation. 1993; 88: 107-115
        • Hicks KA
        • Tcheng JE
        • Bozkurt B
        • Chaitman BR
        • Cutlip DE
        • Farb A
        • et al.
        2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards).
        J Am Coll Cardiol. 2015; 66: 403-469
        • Lang RM
        • Badano LP
        • Mor-Avi V
        • Afilalo J
        • Armstrong A
        • Ernande L
        • et al.
        Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
        J Am Soc Echocardiogr. 2015; 28 (1–39 e14)
      1. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, 3rd, Fleisher LA, Jneid H, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2017;135:e1159–e1195.

        • Bouillanne O
        • Morineau G
        • Dupont C
        • Coulombel I
        • Vincent JP
        • Nicolis I
        • et al.
        Geriatric Nutritional Risk Index: a new index for evaluating at-risk elderly medical patients.
        Am J Clin Nutr. 2005; 82: 777-783
        • Pocock SJ
        • Ariti CA
        • McMurray JJ
        • Maggioni A
        • Kober L
        • Squire IB
        • Meta-Analysis Global Group in Chronic Heart Failure
        Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies.
        Eur Heart J. 2013; 34: 1404-1413
        • Sugano A
        • Seo Y
        • Ishizu T
        • Sai S
        • Yamamoto M
        • Hamada-Harimura Y
        • Machino-Ohtsuka T
        • et al.
        Soluble ST2 and brain natriuretic peptide predict different mode of death in patients with heart failure and preserved ejection fraction.
        J Cardiol. 2019; 73: 326-332
        • Agra Bermejo RM
        • González Ferreiro R
        • Varela Román A
        • Gómez Otero I
        • Kreidieh O
        • Conde Sabarís P
        • et al.
        Nutritional status is related to heart failure severity and hospital readmissions in acute heart failure.
        Int J Cardiol. 2017; 230: 108-114
        • Iwakami N
        • Nagai T
        • Furukawa TA
        • Sugano Y
        • Honda S
        • Okada A
        • et al.
        Prognostic value of malnutrition assessed by Controlling Nutritional Status score for long-term mortality in patients with acute heart failure.
        Int J Cardiol. 2017; 230: 529-536
        • Nishi I
        • Seo Y
        • Hamada-Harimura Y
        • Yamamoto M
        • Ishizu T
        • Sugano A
        • Cardiovascular Assessment Study-Heart Failure Investigators
        GERIATRIC NUTRITIONAL RISK INDEX predicts all-cause deaths in heart failure with preserved ejection fraction.
        ESC Heart Fail. 2019; 6: 396-405
        • Daniels LB
        • Clopton P
        • Iqbal N
        • Tran K
        • Maisel AS
        Association of ST2 levels with cardiac structure and function and mortality in outpatients.
        Am Heart J. 2010; 160: 721-728
        • Colombo PC
        • Onat D
        • Harxhi A
        • Demmer RT
        • Hayashi Y
        • Jelic S
        • et al.
        Peripheral venous congestion causes inflammation, neurohormonal, and endothelial cell activation.
        Eur Heart J. 2014; 35: 448-454
        • Demissei BG
        • Cotter G
        • Prescott MF
        • Felker GM
        • Filippatos G
        • Greenberg BH
        • et al.
        A multimarker multi-time point-based risk stratification strategy in acute heart failure: results from the RELAX-AHF trial.
        Eur J Heart Fail. 2017; 19: 1001-1010