Prognostic value of ST2 in myocardial infarction

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Khadija Mzoughi
Sonia Chouaieb
Ihsen Zairi
Soumaya Fredj
Mouna Ben Kilani
Soumaya Berriri
Mohamed Zili
Sondos Kraiem

Abstract

Introduction: Soluble Suppression of Tumorigenicity 2 (ST2) is a biomarker of myocardial fibrosis increasingly recognized as a predictor of morbidity and mortality in heart failure.
Its role in the prognosis after a myocardial infarction has not been validated to date.

Aim: To evaluate the prognostic value of ST2 for in-hospital morbidity and mortality after myocardial infarction.

Methods: We conducted a longitudinal prospective study including 74 patients admitted for an acute uncomplicated cardiac myocardial infarction at Habib Thameur hospital between April and October 2016. ST2 blood samples were drawn until 72 hours post admission .The primary endpoint was the occurrence of a major cardiovascular event during hospitalization.

Results: Patients’ mean age was 61.28 ± 13 years-old with a sex ratio of 1.8. The reason for admission was acute coronary syndrome with persistent ST segment elevation in 54% of cases and non-ST segment elevation acute myocardial infarction in 46% of cases.
The ST2 assay was positive in 78% of cases with a mean value of 122.43 ± 95.72 ng/ ml. Left ventricular dysfunction was observed in 47% of cases. Fifteen per cent of the patients had a 3 vessel-disease, 24% a 2 vessel-disease and 34% a 1 vessel-disease.
Twenty-six percent had at least one major cardiovascular event. In-hospital mortality was 10%. In multivariate analysis, ST2 was an independent factor associated with the occurrence of major cardiovascular events (RR = 2, p = 0.04). The cutoff value of ST2 of 35 ng/ml had a sensitivity of 95%, a specificity of 30% (AUC = 0.672, CI 0.546-0.798, p = 0.024), a negative predictive value of 100% and a positive value of 33%.
A significant correlation was found between ST2 and troponin, blood glucose on admission, CRP and left ventricular ejection fraction (respectively: r = 0.398, p <0.0001, r = 0.281, p = 0.015, r = 0.245, p = 0.039, r = -0.401, p <0.0001).

Conclusion: The measurement of ST2 after a myocardial infarction constitutes a new prognostic indicator of in-hospital morbidity and mortality.

Keywords:

ST2, myocardial infarction, in-hospital mortality, in-hospital morbidity

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References

  1. Organisation Mondiale de la Santé. Les 10 principales causes de mortalité dans le monde. Genève: OMS ; 2017.
  2. Oueslati C, Delaunay R, Zabalawi A, Payot L, Moquet B. Évolution des délais et de la prise en charge interventionnelle de l'infarctus du myocarde avec sus décalage du ST à la phase aiguë entre 2007 et 2014. Ann Cardiol Angeiol. 2016;65(5):376-7.
  3. Azzaz S, Charbonnel C, Ajlani B, Cherif G, Convers R, Blicq E, et al. Évolution de la prise en charge interventionnelle et des délais de reperfusion à la phase aiguë de l'infarctus du myocarde avec sus-décalage du segment ST. Ann Cardiol Angeiol. 2015;64(5):325-33.
  4. European Society of Cardiology. The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Oxford: ESC; 2017.
  5. De Vreede JJ, Gorgels AP, Verstraaten GM, Vermeer F, Dassen WR, Wellens HJ. Did prognosis after acute myocardial infarction change during the past 30 years? A meta-analysis. J Am Coll Cardiol. 1991;18(3):698-706.
  6. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, et al. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003;163(19):2345-53.
  7. DeBusk RF, Kraemer HC, Nash E, Walter E, Berger, III, Henry L. Stepwise risk stratification soon after acute myocardial infarction. Am J Cardiol. 1983;52(10):1161-6.
  8. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33(20):2569-619.
  9. Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267-315.
  10. Chan D, Ng LL. Biomarkers in acute myocardial infarction. BMC Med. 2010;(8):34.
  11. Sabatine MS, Morrow DA, Higgins LJ, MacGillivray C, Guo W, Bode C, et al. Complementary roles for biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction. Circulation. 2008;117(15):1936-44.
  12. Elosua R. Cardiovascular Risk Functions: Usefulness and Limitations. Rev Esp Cardiol. 2014;67(02):77-9.
  13. Ceconi C, Ferrari R, Bachetti T, Opasich C, Volterrani M, Colombo B, et al. Chromogranin A in heart failure; a novel neurohumoral factor and a predictor for mortality. Eur Heart J. 2002;23(12):967-74.
  14. Desbène C, Gaillard O. Caractéristiques immunoanalytiques de la galectine-3. Ann Biol Clin. 2014;72(4):491-9.
  15. Kempf T, Wollert KC. Growth differentiation factor-15: a new biomarker in cardiovascular disease. Herz. 2009;34(8):594-9.
  16. Sultan A, Cristol JP, Pochic J, Boegner C, Thuan Dit Dieudonné JF, Mariano-Goulard D, et al. O53 Ostéoprotégérine et Risque d'Evènements Cardiovasculaires dans une Population de Diabétiques à Haut Risque : Étude Prospective à Trois Ans. Diabetes & Metabolism. 2008;34 Suppl 3:H26.
  17. Ciccone MM, Cortese F, Gesualdo M, Riccardi R, Di Nunzio D, Moncelli M, et al. A novel cardiac bio-marker: ST2: a review. Molecules. 2013;18(12):15314-28.
  18. Weir RAP, Miller AM, Murphy GEJ, Clements S, Steedman T, Connell JMC, et al. Serum Soluble ST2: A Potential Novel Mediator in Left Ventricular and Infarct Remodeling After Acute Myocardial Infarction. J Am Coll Cardiol. 2010;55(3):243-50.
  19. 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;52(18):1458-65.
  20. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, Colvin MM, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e61.
  21. Saidi O, Ben Mansour N, O'Flaherty M, Capewell S, Critchley JA, Romdhane HB. Analyzing Recent Coronary Heart Disease Mortality Trends in Tunisia between 1997 and 2009. PLoS ONE. 2013;8(5):e63202.
  22. Addad F, Gouider J, Boughzela E, Kamoun S, Boujenah R, Haouala H, et al. Prise en charge de l'infarctus du myocarde en Tunisie : résultats préliminaires du registre FAST-MI Tunisie de la Société tunisienne de cardiologie et de chirurgie cardiovasculaire. Ann Cardiol Angeiol. 2015;64(6):439-45.
  23. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Eur Heart J. 2012;33(20):2551-67.
  24. Dieplinger B, Egger M, Poelz W, Haltmayer M, Mueller T. Long-term stability of soluble ST2 in frozen plasma samples. Clin Biochem. 2010;43(13-14):1169-70.
  25. Lu J, Snider JV, Grenache DG. Establishment of reference intervals for soluble ST2 from a United States population. Clin Chim Acta. 2010;411(21-22):1825-6.
  26. 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;6(6):1172-9.
  27. Kohli P, Bonaca MP, Kakkar R, Kudinova AY, Scirica BM, Sabatine MS, et al. Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial. Clin Chem. 2012;58(1):257-66.
  28. 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.
  29. Pascual-Figal DA, Januzzi JL. The biology of ST2: the International ST2 Consensus Panel. Am J Cardiol. 2015;115(7 Suppl):3b-7b.
  30. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, et al. 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;23(5):479-90.
  31. 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(6):1538-49.
  32. Aldous SJ, Richards AM, Troughton R, Than M. ST2 has diagnostic and prognostic utility for all-cause mortality and heart failure in patients presenting to the emergency department with chest pain. J Card Fail. 2012;18(4):304-10.
  33. Shimpo M, Morrow DA, Weinberg EO, Sabatine MS, Murphy SA, Antman EM, et al. Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction. Circulation. 2004;109(18):2186-90.
  34. Eggers KM, Armstrong PW, Califf RM, Simoons ML, Venge P, Wallentin L, et al. ST2 and mortality in non-ST-segment elevation acute coronary syndrome. Am Heart J. 2010;159(5):788-94.
  35. Dhillon OS, Narayan HK, Quinn PA, Squire IB, Davies JE, Ng LL. Interleukin 33 and ST2 in non-ST-elevation myocardial infarction: comparison with Global Registry of Acute Coronary Events Risk Scoring and NT-proBNP. Am Heart J. 2011;161(6):1163-70.
  36. Demyanets S, Speidl WS, Tentzeris I, Jarai R, Katsaros KM, Farhan S, et al. Soluble ST2 and interleukin-33 levels in coronary artery disease: relation to disease activity and adverse outcome. PLoS One. 2014;9(4):e95055.
  37. Dieplinger B, Egger M, Haltmayer M, Kleber ME, Scharnagl H, Silbernagel G, et al. Increased soluble ST2 predicts long-term mortality in patients with stable coronary artery disease: results from the Ludwigshafen risk and cardiovascular health study. Clin Chem. 2014;60(3):530-40.
  38. Richards AM, Di Somma S, Mueller T. ST2 in stable and unstable ischemic heart diseases. Am J Cardiol. 2015;115(7 Suppl):48b-58b.
  39. Barbarash O, Gruzdeva O, Uchasova E, Dyleva Y, Belik E, Akbasheva O, et al. Prognostic Value of Soluble ST2 During Hospitalization for ST-Segment Elevation Myocardial Infarction. An Lab Med. 2016;36(4):313-9.
  40. Jenkins WS, Roger VL, Jaffe AS, Weston SA, AbouEzzeddine OF, Jiang R, et al. Prognostic Value of Soluble ST2 After Myocardial Infarction: A Community Perspective. Am J Med. 2017;130(9):1112.e9-.e15.
  41. Dhillon OS, Narayan HK, Khan SQ, Kelly D, Quinn PA, Squire IB, et al. Pre-discharge risk stratification in unselected STEMI: Is there a role for ST2 or its natural ligand IL-33 when compared with contemporary risk markers? Int J of Cardiol. 2013;167(5):2182-8.
  42. Seki K, Sanada S, Kudinova AY, Steinhauser ML, Handa V, Gannon J, et al. Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail. 2009;2(6):684-91.
  43. Trajkovic V, Sweet MJ, Xu D. T1/ST2--an IL-1 receptor-like modulator of immune responses. Cytokine & growth factor reviews. 2004;15(2-3):87-95.
  44. Beltrán CJ, Núñez LE, Díazâ€Jiménez D, Farfan N, Candia E, Heine C, et al. Characterization of the novel ST2/ILâ€33 system in patients with inflammatory bowel disease. Inflam Bowel Dis. 2010;16(7):1097-107.