Establishing the Optimal sST2 Cut-off for Predicting 5-Year All-Cause Mortality in Hospitalized Patients with Heart Failure with Reduced Ejection Fraction
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Abstract
Background: Hospitalized patients with chronic heart failure (HF) may experience adverse left ventricular remodeling, systemic and pulmonary congestion, and changes in sST2. Thus, they may require an sST2 cutoff for predicting long-term mortality different from that of patients with stable chronic HF. This study aimed to determine the optimal cutoff value of sST2 predictive of long-term mortality in patients with heart failure with reduced ejection fraction (HFrEF).
Methods: This prospective cohort study included 162 hospitalized patients with HFrEF. Plasma sST2 levels were analyzed. Statistical analyses were performed to evaluate the predictive utility of sST2 levels for all-cause mortality and the optimal cutoff value.
Results: During follow-up, 99 of 162 patients (61.1%) died. The median admission sST2 concentration was 35.3 [19.1-57.3] ng/mL. The cohort-derived cutoff was >27.1 ng/mL (sensitivity, 89.9%; specificity, 84.1%). Patients above this threshold had a higher hazard of 5-year mortality than those with sST2 <=27.1 ng/mL (HR, 6.27; 95% CI, 3.02-13.05; P<0.001). In the reported multivariable model, each 1-unit increase in ln(sST2) was also associated with mortality (adjusted HR, 7.52; 95% CI, 4.07-13.90; P<0.001).
Conclusion: In hospitalized patients with HFrEF, sST2 levels were an independent and associated with 5-year all-cause mortality, and the optimal sST2 cutoff for predicting long-term survival is 27.1 ng/mL.
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24. Felker GM, Anstrom KJ, Adams KF, Ezekowitz JA, Fiuzat M, Houston-Miller N, et al. Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients with Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA. 2017 Aug 22;318(8):713-20.
25. Felker GM, Fiuzat M, Thompson V, Shaw LK, Neely ML, Adams KF, et al. Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and long-term outcomes. Circ Heart Fail. 2013 Nov;6(6):1172-9.
2. Dokainish H, Teo K, Zhu J, Roy A, AlHabib KF, ElSayed A, et al. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study. Lancet Glob Health. 2017 Jul;5(7):e665-e672.
3. Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol. 2011 Jan;8(1):30-41.
4. Reyes EB, Ha JW, Firdaus I, Ghazi AM, Phrommintikul A, Sim D, et al. Heart failure across Asia: Same healthcare burden but differences in organization of care. Int J Cardiol. 2016 Nov 15;223:163-7.
5. Gheorghiade M, Vaduganathan M, Fonarow GC, Bonow RO. Rehospitalization for heart failure: problems and perspectives. J Am Coll Cardiol. 2013 Jan 29;61(4):391-403.
6. Taylor CJ, Ryan R, Nichols L, Gale N, Hobbs FR, Marshall T. Survival following a diagnosis of heart failure in primary care. Fam Pract. 2017 Apr 1;34(2):161-8.
7. Dieplinger B, Mueller T. Soluble ST2 in heart failure. Clin Chim Acta. 2015 Mar 30;443:57-70.
8. Richards AM. ST2 and Prognosis in Chronic Heart Failure. J Am Coll Cardiol. 2018 Nov 6;72(19):2321-23.
9. 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 Feb 11;107(5):721-6.
10. Emdin M, Aimo A, Vergaro G, Bayes-Genis A, Lupón 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 Nov 6;72(19):2309-20.
11. Aimo A, Vergaro G, Passino C, Ripoli A, Ky B, Miller WL, et al. Prognostic Value of Soluble Suppression of Tumorigenicity-2 in Chronic Heart Failure: A Meta-Analysis. JACC Heart Fail. 2017 Apr;5(4):280-6.
12. Rahimi K, Bennett D, Conrad N, Williams TM, Basu J, Dwight J, et al. Risk prediction in patients with heart failure: a systematic review and analysis. JACC Heart Fail. 2014 Oct;2(5):440-6.
13. Wang K, Ni G, Wu Q, Zhou Y, Yao W, Zhang H, et al. Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide and Glomerular Filtration Rate in Patients with Acute Heart Failure. Front Cardiovasc Med. 2020 Jul 21;7:123.
14. Gardner RS, Ozalp F, Murday AJ, Robb SD, McDonagh TA. N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure. Eur Heart J. 2003 Oct;24(19):1735-43.
15. Sarhene M, Wang Y, Wei J, Huang Y, Li M, Li L, et al. Biomarkers in heart failure: the past, current and future. Heart Fail Rev. 2019 Nov;24(6):867-903.
16. Vasan RS, Urbina EM, Jin L, Xanthakis V. Prognostic Significance of Echocardiographic Measures of Cardiac Remodeling in the Community. Curr Cardiol Rep. 2021 Jun 3;23(7):86.
17. Daubert MA, Adams K, Yow E, Barnhart HX, Douglas PS, Rimmer S, et al. NT-proBNP Goal Achievement Is Associated with Significant Reverse Remodeling and Improved Clinical Outcomes in HFrEF. JACC Heart Fail. 2019 Feb;7(2):158-168.
18. Bertero E, Maack C. Metabolic remodeling in heart failure. Nat Rev Cardiol. 2018;15:457-70.
19. Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE. Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging. 2011 Jan;4(1):98-108.
20. Khan S, Rasool ST. Current Use of Cardiac Biomarkers in Various Heart Conditions. Endocr Metab Immune Disord Drug Targets. 2021;21(6):980-93.
21. Ahmad T, Fiuzat M, Neely B, Neely ML, Pencina MJ, Kraus WE, et al. Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure. JACC Heart Fail. 2014 Jun;2(3):260-8.
22. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032.
23. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-726.
24. Felker GM, Anstrom KJ, Adams KF, Ezekowitz JA, Fiuzat M, Houston-Miller N, et al. Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients with Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA. 2017 Aug 22;318(8):713-20.
25. Felker GM, Fiuzat M, Thompson V, Shaw LK, Neely ML, Adams KF, et al. Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and long-term outcomes. Circ Heart Fail. 2013 Nov;6(6):1172-9.
| Files | ||
| Issue | Vol 21 No 3 (2026) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/rhythm.v21i3.22565 | |
| Keywords | ||
| Heart Failure Soluble Suppression of Tumorigenesis 2 (sST2) Prognosis Heart Failure with Reduced Ejection Fraction (HFrEF) | ||
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How to Cite
1.
Nguyen K, Hoang S, Bui D, Le T, Tran L. Establishing the Optimal sST2 Cut-off for Predicting 5-Year All-Cause Mortality in Hospitalized Patients with Heart Failure with Reduced Ejection Fraction. Res Heart Yield Transl Med. 2026;21(3):221-230.
