sST2 Level at Decompensated Chronic Heart Failure in Patients with Dilated Cardiomyopathy

Khumoyun A. Gulomov, Timur A. Abdullaev, Igor A. Tsoi, Adolat V. Ziyaeva

 
International Journal of Biomedicine. 2022;12(2):222-226.
DOI: 10.21103/Article12(2)_OA3
Originally published June 5, 2022

Abstract: 

The purpose of the study was to evaluate the relationship between clinical and functional changes and sST2 levels in patients with dilated cardiomyopathy (DCM) admitted to the hospital due to decompensated chronic heart failure (CHF).
Methods and Results:The study involved 64 DCM patients with clinical signs of decompensated CHF. According to the sST2 level, the patients were divided into two groups. Group 1 included 30 patients with sST2 level <35ng/ml; Group 2 included 34 patients with sST2 level ≥35ng/ml. All patients underwent the following examinations: collection of anamnestic data, physical examination, general clinical and laboratory blood tests, 12-lead ECG, conventional 2D echocardiography in M- and B-modes, the 6MWT, and the assessment of the quality of life according to the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The serum level of sST2 was determined by enzyme immunoassay using the Presage ST2 Assay.
The duration of CHF was significantly longer in Group 2 than in Group 1(48.7±6.5 mth versus 29.6±7 mth P<0.05), and the number of hospitalizations per year was more frequent (Table 1). Group 2 patients were characterized by lower blood pressure levels and high heart rate (P<0.05). At the same time, the 6MWT value was lower and MLHFQ score was higher in Group 2 than in Group 1 (P<0.001 in both cases). In Group 1, LVEF was significantly higher and LVM was significantly lower than in Group 2 (P<0.001). All in all, Group 2 patients had more pronounced disorders in LV systolic dysfunction (Table 3). The correlation analysis revealed an inverse correlation between the sST2 level and 6MWT (r=-0.69, P<0.01), as well as LVEF (r=-0.26, P<0.01). Statistically significant direct correlations were found between the sST2evel and the size and volume of the LV cavities.
Conclusion: sST2 is a clinically relevant biomarker that reflects pathophysiological processes and provides prognostic information in the setting of DCM, especially in patients with HF.

Keywords: 
soluble suppression of tumorigenecity 2 • dilated cardiomyopathy • heart failure
References: 
  1. Moiseev VI. [Genetics of cardiomyopathies]. Kardiologiia. 2003;43(3):85-9. [Article in Russian].
  2. Moiseev VS, Kiiakbaev GK. [The problem of classification of cardiomyopathies]. Kardiologiia. 2009;49(1):65-70.  [Article in Russian].
  3. Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov. 2008 Oct;7(10):827-40. doi: 10.1038/nrd2660. 
  4. Weinberg EO, Shimpo M, De Keulenaer GW, MacGillivray C, Tominaga S, Solomon SD, Rouleau JL, Lee RT. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation. 2002 Dec 3;106(23):2961-6. doi: 10.1161/01.cir.0000038705.69871.d9. 
  5. Weir RA, Miller AM, Murphy GE, Clements S, Steedman T, Connell JM, McInnes IB, Dargie HJ, McMurray JJ. Serum soluble ST2: a potential novel mediator in left ventricular and infarct remodeling after acute myocardial infarction. J Am Coll Cardiol. 2010 Jan 19;55(3):243-50. doi: 10.1016/j.jacc.2009.08.047. 
  6. Pascual-Figal DA, Januzzi JL. The biology of ST2: the International ST2 Consensus Panel. Am J Cardiol. 2015 Apr 2;115(7 Suppl):3B-7B. doi: 10.1016/j.amjcard.2015.01.034.
  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. 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. 2005 Nov;23(5):479-90. doi: 10.1016/j.immuni.2005.09.015. 
  8. Andreasová T, Vránová J, Vondráková D, Sedláčková L, Zákostelská ZJ, Neužil P, Málek F. Role of biomarkers of cardiac remodeling, myofibrosis, and inflammation in assessment of disease severity in euvolemic patients with chronic stable heart failure. J Int Med Res. 2020 Aug;48(8):300060520947869. doi: 10.1177/0300060520947869. 
  9. Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immunol. 2016 Nov;16(11):676-689. doi: 10.1038/nri.2016.95.
  10. Villacorta H, Maisel AS. Soluble ST2 Testing: A Promising Biomarker in the Management of Heart Failure. Arq Bras Cardiol. 2016 Feb;106(2):145-52. doi: 10.5935/abc.20150151.
  11. Zhang T, Xu C, Zhao R, Cao Z. Diagnostic Value of sST2 in Cardiovascular Diseases: A Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2021 Jul 23;8:697837. doi: 10.3389/fcvm.2021.697837. 
  12. Parikh RH, Seliger SL, Christenson R, Gottdiener JS, Psaty BM, deFilippi CR. Soluble ST2 for Prediction of Heart Failure and Cardiovascular Death in an Elderly, Community-Dwelling Population. J Am Heart Assoc. 2016 Aug 1;5(8):e003188. doi: 10.1161/JAHA.115.003188.
  13. Marino R, Magrini L, Orsini F, Russo V, Cardelli P, Salerno G, Hur M, Di Somma S; GREAT NETWORK. Comparison Between Soluble ST2 and High-Sensitivity Troponin I in Predicting Short-Term Mortality for Patients Presenting to the Emergency Department With Chest Pain. Ann Lab Med. 2017 Mar;37(2):137-146. doi: 10.3343/alm.2017.37.2.137. 
  14. Dudek M, Kałużna-Oleksy M, Migaj J, Straburzyńska-Migaj E. Clinical value of soluble ST2 in cardiology. Adv Clin Exp Med. 2020 Oct;29(10):1205-1210. doi: 10.17219/acem/126049. 
  15. Emdin M, Aimo A, Vergaro G, Bayes-Genis A, Lupón J, Latini R, Meessen J, Anand IS, Cohn JN, Gravning J, Gullestad L, Broch K, Ueland T, Nymo SH, Brunner-La Rocca HP, de Boer RA, Gaggin HK, Ripoli A, Passino C, Januzzi JL Jr. sST2 Predicts Outcome in Chronic Heart Failure Beyond NT-proBNP and High-Sensitivity Troponin T. J Am Coll Cardiol. 2018 Nov 6;72(19):2309-2320. doi: 10.1016/j.jacc.2018.08.2165.
  16. McCarthy CP, Januzzi JL Jr. Soluble ST2 in Heart Failure. Heart Fail Clin. 2018 Jan;14(1):41-48. doi: 10.1016/j.hfc.2017.08.005.
  17. 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; 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. 2013 Oct 15;62(16):e147-239. doi: 10.1016/j.jacc.2013.05.019.
  18. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016 Aug;18(8):891-975. doi: 10.1002/ejhf.592.
  19. McKie PM, Burnett JC Jr. NT-proBNP: The Gold Standard Biomarker in Heart Failure. J Am Coll Cardiol. 2016 Dec 6;68(22):2437-2439. doi: 10.1016/j.jacc.2016.10.001.
  20. 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. doi: 10.1161/01.cir.0000047274.66749.fe.
  21. Ky B, French B, McCloskey K, Rame JE, McIntosh E, Shahi P, et al. High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail. 2011;4(2):180–7. 
  22. Kuster N, Huet F, Dupuy AM, Akodad M, Battistella P, Agullo A, Leclercq F, Kalmanovich E, Meilhac A, Aguilhon S, Cristol JP, Roubille F. Multimarker approach including CRP, sST2 and GDF-15 for prognostic stratification in stable heart failure. ESC Heart Fail. 2020 Oct;7(5):2230-2239. doi: 10.1002/ehf2.12680.
  23. Rehman SU, Mueller T, Januzzi JL Jr. Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure. J Am Coll Cardiol. 2008 Oct 28;52(18):1458-65. doi: 10.1016/j.jacc.2008.07.042. 
  24. Januzzi JL Jr. ST2 as a cardiovascular risk biomarker: from the bench to the bedside. J Cardiovasc Transl Res. 2013 Aug;6(4):493-500. doi: 10.1007/s12265-013-9459-y. 
  25. Manzano-Fernández S, Mueller T, Pascual-Figal D, Truong QA, Januzzi JL. Usefulness of soluble concentrations of interleukin family member ST2 as predictor of mortality in patients with acutely decompensated heart failure relative to left ventricular ejection fraction. Am J Cardiol. 2011 Jan 15;107(2):259-67. doi: 10.1016/j.amjcard.2010.09.011. 
  26. Dieplinger B, Januzzi JL Jr, Steinmair M, Gabriel C, Poelz W, Haltmayer M, Mueller T. 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. 2009 Nov;409(1-2):33-40. doi: 10.1016/j.cca.2009.08.010. 
  27. 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. Heart failure therapy-induced early ST2 changes may offer long-term therapy guidance. J Card Fail. 2013 Dec;19(12):821-8. doi: 10.1016/j.cardfail.2013.11.003. 
  28. You H, Jiang W, Jiao M, Wang X, Jia L, You S, Li Y, Wen H, Jiang H, Yuan H, Huang J, Qiao B, Yang Y, Jin M, Wang Y, Du J. Association of Soluble ST2 Serum Levels With Outcomes in Pediatric Dilated Cardiomyopathy. Can J Cardiol. 2019 Jun;35(6):727-735. doi: 10.1016/j.cjca.2019.02.016.
  29. Binas D, Daniel H, Richter A, Ruppert V, Schlüter KD, Schieffer B, Pankuweit S. The prognostic value of sST2 and galectin-3 considering different aetiologies in non-ischaemic heart failure. Open Heart. 2018 Feb 26;5(1):e000750. doi: 10.1136/openhrt-2017-000750. 
  30. Jirak P, Lichtenauer M, Wernly B, Paar V, Jung C, Yilmaz A, et al. P6287 Analysis of novel cardiac markers sST2 and IL-33 in chronic heart failure with reduced ejection fraction, European Heart Journal. 2019;40 (Issue Supplement_1), October 2019, ehz746.0885,
  31. Lupón J, Gaggin HK, de Antonio M, Domingo M, Galán A, Zamora E, et al. Biomarker-assist score for reverse remodelling prediction in heart failure: the ST2-R2 score. Int J Cardiol. 2015;184:337–43.
  32. Wojciechowska C, Romuk E, Nowalany-Kozielska E, Jacheć W. Serum Galectin-3 and ST2 as predictors of unfavorable outcome in stable dilated cardiomyopathy patients. Hellenic J Cardiol. 2017 Sep-Oct;58(5):350-359. doi: 10.1016/j.hjc.2017.03.006. 

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Received February 134, 2022.
Accepted May 1, 2022.
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