Skip to main content
SpringerLink
Log in

Prognostic value of sST2 added to BNP in acute heart failure with preserved or reduced ejection fraction

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

Natriuretic peptides and suppression of tumorigenicity 2 (ST2) represent two different physiopathological pathways. We evaluated the prognostic accuracy and complementarity of B-type natriuretic peptide (BNP) and soluble ST2 (sST2) plasma levels at discharge from a hospital admission for acute heart failure, both in patients with preserved (HFpEF) and depressed (HFrEF) systolic function.

Methods and results

We enrolled 195 consecutive patients discharged alive and followed them prospectively for 6 months. The endpoint was all-cause death or hospital readmission for heart failure. Seventy-six patients had HFpEF and 119 had HFrEF, of whom 23 (30.3 %) and 43 (36.1 %) reached the combined endpoint, respectively. In both HFpEF and HFrEF, having the two biomarkers into account added prognostic information, with the highest risk in patients with both biomarkers above the median in their group (approximately 40 % hospitalization-free survival in both groups at 6 months). These associations translated into a significant fourfold increase in risk of the endpoint for one elevated biomarker and sevenfold for both biomarkers elevated in HFrEF, and no association for one elevated biomarker and fivefold increase in risk for both biomarkers elevated in HFpEF. Considering the reclassification of risk added to BNP by measurement of sST2, net reclassification index was 0.31 (p = 0.21) among patients with HFpEF and 0.70 (p < 0.001) among patients with HFrEF.

Conclusions

sST2 provides robust prognostic information in acute heart failure with HFrEF, while this pattern was less clear in HFpEF. When sST2 was measured together with BNP, it improved prognostic accuracy in both groups, more clearly in HFrEF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Braunwald E (2008) Biomarkers in heart failure. N Engl J Med 358(20):2148–2159

    Article  CAS  PubMed  Google Scholar 

  2. Maisel A, Mueller C, Adams K Jr, Anker SD, Aspromonte N, Cleland JG, Cohen-Solal A, Dahlstrom U, DeMaria A, Di Somma S, Filippatos GS, Fonarow GC, Jourdain P, Komajda M, Liu PP, McDonagh T, McDonald K, Mebazaa A, Nieminen MS, Peacock WF, Tubaro M, Valle R, Vanderhyden M, Yancy CW, Zannad F, Braunwald E (2008) State of the art: using natriuretic peptide levels in clinical practice. Eur J Heart Fail 10(9):824–839

    Article  CAS  PubMed  Google Scholar 

  3. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P (2012) ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 14:803–869

    Article  CAS  PubMed  Google Scholar 

  4. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL (2013) American College of Cardiology Foundation; 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. 62(16):e147–e239

    Article  PubMed  Google Scholar 

  5. Dale M, Nicklin MJ (1999) Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1 Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q. Genomics 57(1):177–179

    Article  CAS  PubMed  Google Scholar 

  6. Iwahana H, Yanagisawa K, Ito-Kosaka A, Kuroiwa K, Tago K, Komatsu N, Katashima R, Itakura M, Tominaga S (1999) Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells. Eur J Biochem 264(2):397–406

    Article  CAS  PubMed  Google Scholar 

  7. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23(5):479–490

    Article  CAS  PubMed  Google Scholar 

  8. Weinberg EO, Shimpo M, De Keulenaer GW, MacGillivray C, Tominaga S, Solomon SD, Rouleau JL, Lee RT (2002) Expression and regulation of ST2, an interleukin-1 receptor family member in cardiomyocytes and myocardial infarction. Circulation 106(23):2961–2966

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Sanada S, Hakuno D, Higgins LJ, Schreiter ER, McKenzie AN, Lee RT (2007) IL-33 and ST2 comprise a critical biochemically induced and cardioprotective signaling system. J Clin Invest 117(6):1538–1549

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Seki K, Sanada S, Kudinova AY, Steinhauser ML, Handa V, Gannon J, Lee RT (2009) Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail 2(6):684–691

    Article  CAS  PubMed  Google Scholar 

  11. Mueller T, Dieplinger B, Gegenhuber A, Poelz W, Pacher R, Haltmayer M (2008) Increased plasma concentrations of soluble ST2 are predictive for 1-year mortality in patients with acute destabilized heart failure. Clin Chem 54(4):752–756

    Article  CAS  PubMed  Google Scholar 

  12. Henry-Okafor Q, Collins SP, Jenkins CA, Miller KF, Maron DJ, Naftilan AJ, Weintraub N, Fermann GJ, McPherson J, Menon S, Sawyer DB, Storrow AB (2012) Soluble ST2 as a diagnostic and prognostic marker for acute heart failure syndromes. Open Biomark J 2012(5):1–8

    Article  PubMed Central  PubMed  Google Scholar 

  13. Lassus J, Gayat E, Mueller C, Peacock WF, Spinar J, Harjola VP, van Kimmenade R, Pathak A, Mueller T, Disomma S, Metra M, Pascual-Figal D, Laribi S, Logeart D, Nouira S, Sato N, Potocki M, Parenica J, Collet C, Cohen-Solal A, Januzzi JL Jr (2013) Mebazaa A; GREAT-Network. 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. Int J Cardiol 168(3):2186–2194

    Article  PubMed  Google Scholar 

  14. Bishu K, Redfield MM (2013) Acute heart failure with preserved ejection fraction: unique patient characteristics and targets for therapy. Curr Heart Fail Rep 10(3):190–197

    Article  PubMed  Google Scholar 

  15. Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27(2):157–172

    Article  PubMed  Google Scholar 

  16. Blair JE, Zannad F, Konstam MA, Cook T, Traver B, Burnett JC Jr, Grinfeld L, Krasa H, Maggioni AP, Orlandi C, Swedberg K, Udelson JE, Zimmer C, Gheorghiade C (2008) EVEREST Investigators. Continental differences in clinical characteristics, management, and outcomes in patients hospitalized with worsening heart failure: results from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: outcome Study with Tolvaptan) program. J Am Coll Cardiol 52(20):1640–1648

    Article  PubMed  Google Scholar 

  17. Manzano-Fernández S, Mueller T, Pascual-Figal D, Truong QA, Januzzi JL (2011) Usefulness of soluble concentrations on interleukin family member ST2 as predictor of mortality in patients with acutely decompensated heart failure relative to left ventricular ejection fraction. Am J Cardiol 107(2):259–267

    Article  PubMed Central  PubMed  Google Scholar 

  18. Kossaify A, Garcia A, Succar S, Ibrahim A, Moussallem N, Kossaify M (2013) Grollier G; STAR-P Consortium. Perspectives on the value of biomarkers in acute cardiac care and implications for strategic management. Biomark Insights. 3(8):115–126

    Article  Google Scholar 

  19. Lee DS, Vasan RS (2005) Novel markers for heart failure diagnosis and prognosis. Curr Opin Cardiol 20(3):201–210

    Article  PubMed  Google Scholar 

  20. Gaggin HK, Januzzi JL Jr (2013) Biomarkers and diagnostics in heart failure. Biochim Biophys Acta 1832(12):2442–2450

    Article  CAS  PubMed  Google Scholar 

  21. Doust JA, Pietrzak E, Dobson A, Glasziou P (2005) How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure; systematic review. BMJ 330(7492):625

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Felker GM, Hasselblad V, Hernandez AF, O’Connor CM (2009) Biomarker-guided therapy in chronic heart failure: a meta-analysis of randomized controlled trials. Am Heart J 158(3):422–430

    Article  CAS  PubMed  Google Scholar 

  23. Dieplinger B, Januzzi JL Jr, Steinmair M, Gabriel C, Poelz W, Haltmayer M, Mueller T (2009) Analytical and clinical evaluation of a novel high-sensitivity assay for measurement of soluble ST2 in human plasma—the Presage ST2 assay. Clin Chim Acta 409(1–2):33–40

    Article  CAS  PubMed  Google Scholar 

  24. Fonarow GC, Peacock WF, Phillips CO, Givertz MM, Lopatin M (2007) ADHERE Scientific Advisory Committee and Investigators. Admission B-type natriuretic peptide levels and in-hospital mortality in acute decompensated heart failure. J Am Coll Cardiol 49(19):1943–1950

    Article  CAS  PubMed  Google Scholar 

  25. Kociol RD, Horton JR, Fonarow GC, Reyes EM, Shaw LK, O’Connor CM, Felker GM, Hernandez AF (2011) Admission, discharge, or change in B-type natriuretic peptide and long-term outcomes: data from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) linked to Medicare claims. Circ Heart Fail 4(5):628–636

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Januzzi JL Jr, Peacock WF, Maisel AS, Chae CU, Jesse RL, Baggish AL, O’Donoghue M, Sakhuja R, Chen AA, van Kimmenade RR, Lewandrowski KB, Lloyd-Jones DM, Wu AH (2007) 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. J Am Coll Cardiol 50(7):607–613

    Article  CAS  PubMed  Google Scholar 

  27. Rose-Jones LJ, Rommel JJ (2014) Chang PP. Heart failure with preserved ejection fraction: an ongoing enigma. Cardiol Clin 32(1):151–161

    Article  PubMed  Google Scholar 

  28. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355(3):251–259

    Article  CAS  PubMed  Google Scholar 

  29. Steinberg BA, Zhao X, Heidenreich PA, Peterson ED, Bhatt DL, Cannon CP, Hernandez AF (2012) Fonarow GC; Get With the Guidelines Scientific Advisory Committee and Investigators. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies and outcomes. Circulation 126(1):65–75

    Article  PubMed  Google Scholar 

  30. Pascual-Figal DA, Manzano-Fernández S, Boronat M, Casas T, Garrido IP, Bonaque JC, Pastor-Perez F, Valdés M, Januzzi JL (2011) Soluble ST2, high sensitivity troponin T- and N-terminal pro-B-type natriuretic peptide: complementary role for risk stratification in acutely decompensated heart failure. Eur J Heart Fail 13(7):718–725

    Article  CAS  PubMed  Google Scholar 

  31. Manzano-Fernández S, Januzzi JL, Pastor-Pérez FJ, Bonaque-González JC, Boronat-Garcia M, Pascual-Figal DA, Montalban-Larrea S, Navarro-Peñalver M, Andreu-Cayuelas JM, Valdés M (2012) Serial monitoring of soluble interleukin family member ST2 in patients with acutely decompensated heart failure. Cardiology 122(3):158–166

    Article  PubMed  Google Scholar 

  32. Breidthardt T, Balmelli C, Twerenbold R, Mosimann T, Espinola J, Haaf P, Thalmann G, Moehring B, Mueller M, Meller B, Reichlin T, Murray K, Ziller R, Benkert P, Osswald S, Mueller C (2013) Heart failure therapy-induced early ST2 changes may offer long-term therapy guidance. J Card Fail 19(12):821–828

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from Fundação para a Ciência e Tecnologia, Lisbon, Portugal (PIC/IC/82773/2007). Dr Januzzi is supported in part by the DeSanctis Clinical Scholar Endowment.

Conflict of interest

Dr Januzzi receives Grants from Roche, Siemens, Thermo Fisher and Singulex, is a consultant for Roche, Critical Diagnostics, diaDexus and Novartis; CEC/DMC: Amgen, Novartis, Boeringer-Ingelheim. The remaining authors declare they have no conflict of interest.

Ethical standard

The study protocol conforms to the ethical principles of the 1964 Declaration of Helsinki and its later amendments and was approved by the local ethics committee; all patients provided written informed consent prior to their inclusion in the study.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, São João Hospital Centre, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

    Fernando Friões, Patrícia Lourenço & Paulo Bettencourt

  2. Department of Medicine, University of Porto Medical School, Porto, Portugal

    Fernando Friões, Patrícia Lourenço & Paulo Bettencourt

  3. EPIUnit-Institute of Public Health, University of Porto (ISPUP), Porto, Portugal

    Olga Laszczynska, João-Tiago Guimarães & Ana Azevedo

  4. Department of Cardiology, São João Hospital Centre, Porto, Portugal

    Pedro-Bernardo Almeida

  5. Department of Pathology, São João Hospital Centre, Porto, Portugal

    João-Tiago Guimarães

  6. Department of Biochemistry, University of Porto Medical School, Porto, Portugal

    João-Tiago Guimarães

  7. Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA

    James L. Januzzi

  8. Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal

    Ana Azevedo

Authors
  1. Fernando Friões
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrícia Lourenço
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olga Laszczynska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pedro-Bernardo Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. João-Tiago Guimarães
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. James L. Januzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ana Azevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Paulo Bettencourt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fernando Friões.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Friões, F., Lourenço, P., Laszczynska, O. et al. Prognostic value of sST2 added to BNP in acute heart failure with preserved or reduced ejection fraction. Clin Res Cardiol 104, 491–499 (2015). https://doi.org/10.1007/s00392-015-0811-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-015-0811-x

Keywords

Search

Navigation