Suppression of tumorigenicity-2 (ST2) is a relatively new biomarker that is believed to reflect myocardial wall stress and activation of the fibrosis pathway. Suppression of tumorigenicity-2 is a strong predictor of cardiovascular mortality and rehospitalization in both acute and chronic heart failure (HF). Suppression of tumorigenicity-2 has a prognostic value independent of natriuretic peptides (NPs) and some studies have shown it is even superior in terms of risk of stratification. It is the most promising biomarker in the field of HF since the introduction of NPs. The main objective of future research is to determine if ST2-guided therapy would have a benefit on patient symptoms and HF progression
Mosterd, A, AW Hoes. Clinical epidemiology of heart failure. – Heart, 2007;93: 1137-1146.
Mahmood, SS, TJ Wang. The epidemiology of congestive heart failure: the Framingham Heart Study perspective. – Global Heart, 2013; 8(1): 77-82.
Braunwald E. Biomarkers in heart failure. N Engl J Med 2008;358:2148–59.
Pascual-Figal DA, Januzzi JL. The biology of ST2: the International ST2 Consensus Panel. Am J Cardiol 2015;115:3B–7B.
Tominaga S. A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor. FEBS Lett1989;258:301–304.
Werenskiold AK, Hoffmann S, Klemenz R. Induction of a mitogen responsive gene after expression of the Ha-ras oncogene in NIH 3T3fibroblasts. Mol Cell Biol 1989;9:5207–14.
Weinberg EO, Shimpo M, De Keulenaer GW, MacGillivray C, Tominaga S, Solomon SD, et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation 2002;106(23):2961-6).
Sanada S, Hakuno D, Higgins LJ, et al. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest 2007;117:1538–49.)
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 cytokyne that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokynes.Immunity 2005;23:479–490.
Truong QA, Januzzi JL, Szymonifka J, et al. Coronary sinus biomarker sampling compared to peripheral venous blood for predicting outcomes in patients with severe heart failure undergoing cardiac resynchronization therapy: the BIOCRT study. Heart Rhythm 2014;11:2167–75
AbouEzzeddine OF, McKie PM, Dunlay SM, et al. Suppression of tumorigenicity 2 in heart failure with preserved ejection fraction. J Am Heart Assoc 2017;6:e004382
Pascual-Figal DA, Pérez-Martínez MT, AsensioLopez MC, et al. Pulmonary production of soluble ST2 in heart failure. Circ Heart Fail 2018;11: e005488.
Mueller T, Zimmermann M, Dieplinger B, Ankersmit HJ, Haltmayer M. Comparison of plasma concentrations of soluble ST2 measured by three different commercially available assays: The MBL ST2 assay, the Presage ST2 Assay, and the R&D ST2 assay. Clin. Chim. Acta 413(19–20), 1493–1494 (2012).
Januzzi JL Jr, Peacock WF, Maisel AS, Chae CU, Jesse RL, Baggish AL, et al. 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. 2007;50(7):607-13
Shah R, Chen-Tournoux A, Picard M, van Kimmenade R, Januzzi JL. Serum levels of the interleukin-1 receptor family member ST2, cardiac structure and function, and long-term mortality in patients with acute dyspnea. Circ Heart Fail. 2009;2(4):311-9
Aimo A, Vergaro G, Ripoli A, Bayes-Genis A, Pascual Figal DA, de Boer RA, Lassus J, Mebazaa A, Gayat E, Breidthardt T, Sabti Z, Mueller C, Brunner-La Rocca HP, Tang WH, Grodin JL, Zhang Y, Bettencourt P, Maisel AS, Passino C, Januzzi JL, Emdin M. Meta-Analysis of Soluble Suppression of Tumorigenicity-2 and Prognosis in Acute Heart Failure. JACC Heart Fail. 2017 Apr;5(4):287-296. doi: 10.1016/j.jchf.2016.12.016. Epub 2017 Feb 8. PMID: 28189578.
Boisot S, Beede J, Isakson S, Chiu A, Clopton P, Januzzi J, Maisel AS, Fitzgerald RL. Serial sampling of ST2 predicts 90-day mortality following destabilized heart failure. J Card Fail. 2008 Nov;14(9):732-8. doi: 10.1016/j.cardfail.2008.06.415. Epub 2008 Jul 26. PMID: 18995177.
van Vark LC, Lesman-Leegte I, Baart SJ, Postmus D, Pinto YM, Orsel JG, Westenbrink BD, Brunner-la Rocca HP, van Miltenburg AJM, Boersma E, Hillege HL, Akkerhuis KM; TRIUMPH Investigators. Prognostic Value of Serial ST2 Measurements in Patients With Acute Heart Failure. J Am Coll Cardiol. 2017 Nov 7;70(19):2378-2388. doi: 10.1016/j.jacc.2017.09.026. PMID: 29096809.
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. Epub 2013 Nov 14. PMID: 24239955.
Ky B, French B, McCloskey K, et al. Highsensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail 2011;4: 180–7.
Gruson D, Lepoutre T, Ahn SA, Rousseau MF. Increased soluble ST2 is a stronger predictor of long-term cardiovascular death than natriuretic peptides in heart failure patients with reduced ejection fraction. Int J Cardiol 2014;172:e250–e252
Felker GM, Fiuzat M, Thompson V, et al. Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and longterm outcomes. Circ Heart Fail 2013;6:1172–9
Gaggin HK, Motiwala S, Bhardwaj A, Parks KA, Januzzi JL Jr. Soluble concentrations of the interleukin receptor family member ST2 and β-blocker therapy in chronic heart failure. Circ Heart Fail. 2013 Nov;6(6):1206-13. doi: 10.1161/CIRCHEARTFAILURE.113.000457. Epub 2013 Oct 10. PMID: 24114865.
Mueller T, Gegenhuber A, Leitner I, Poelz W, Haltmayer M, Dieplinger B. Diagnostic and prognostic accuracy of galectin-3 and soluble ST2 for acute heart failure. Clin Chim Acta. 2016 Dec 1;463:158-164. doi: 10.1016/j.cca.2016.10.034. Epub 2016 Oct 29. PMID: 27983996.
Bayes-Genis A, De Antonio M, Villa J, Pe~nafiel J, Galan A, Barallat J, Zamora E, Urrutia A, Lupon J. Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart failure risk stratification: ST2 versus galectine-3.J Am Coll Cardiol2014;63:158–166
Skali H, Gerwien R, Meyer TE, Snider JV, Solomon SD, Stolen CM. Soluble ST2 and Risk of Arrhythmias, Heart Failure, or Death in Patients with Mildly Symptomatic Heart Failure: Results from MADIT-CRT. J Cardiovasc Transl Res. 2016 Dec;9(5-6):421-428. doi: 10.1007/s12265-016-9713-1. Epub 2016 Oct 31. PMID: 27798759.
Januzzi JL, Horne BD, Moore SA, Galenko O, Snow GL, Brunisholz KD, Muhlestein JB, Alharethi R, Carlquist JF, Budge D, Rasmussen K, Kfoury AG. Interleukin receptor family member ST2 concentrations in patients following heart transplantation. Biomarkers. 2013 May;18(3):250-6. doi: 10.3109/1354750X.2013.773081. Epub 2013 Apr 5. PMID: 23557127.
Yancy CW, Jessup M, Bozcurt B, Butler J, Casey DE Jr, Drazner MH, et al; 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;62(16): e147-239
Ponikowski P, Voors AA, Anker SD, et al. 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;18: 891–975.
