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Head to Head Comparison of Suppression of Tumorogenicity 2 and Copeptin Significance for Prognosis of Patients After Acute Heart Failure Decompensation

Skvortsov A. A.1, Protasov V. N.1, Narusov O. Yu.1, Koshkina D. E.2, Osmolovskaya Yu. F.1, Kuznetzova T. V.1, Masenko V. P.1, Tereschenko S. N.1
1 - Institute of Cardiology of Russian Cardiology Scientific and Production Complex, Moscow, Russia
2 - Federal State Institution National Research Center for Preventive Medicine, Moscow, Russia

Keywords: chronic heart failure; heart failure decompensation; risk stratification; soluble ST2 receptor; copeptin

DOI: 10.18087/cardio.2017.9.10028

Purpose. To assess the suppression of tumorogenicity 2 (ST2) and copeptin significance for risk stratification of patient (pts) with acute decompensated heart failure (ADHF) during long-term follow-up compared with traditional risk factors. Methods. We included in a prospective study 159 pts with ADHF. Blood samples to determine copeptin, sST2, NT-proBNP and hsTnT concentration were collected at admission and at discharge from the hospital. Serial determination of biomarker concentration was performed at 3, 6 and 12 months of follow-up. The combined primary end point of the trial included cardiovascular (CV) death, hospitalization due to HF, episodes of HF deterioration requiring additional intravenous diuretics and CV death with successful resuscitation. Results. During 1-year follow-up (295.3±113.2 days) 56 pts (35.2%) had 78 (49.1%) cardiovascular events. Biomarker concentrations in low risk pts (without CV events) were significantly lower compared with high risk pts (with CV events). Discharge copeptin and NT-proBNP values were comparable for pts risk stratification: AUC=0.727 (95% CI 0.637–0.816), р<0.0001, and AUC=0.735 (0.640;0,830) p<0.0001, but sST2 concentrations had the most predictive capacity relative primary end point during 1-year follow-up: AUC=0.768 (95% CI 0.682–0.854), р<0.0001. Maximally sST2 values were predictive for 180 days period of follow-up: AUC=0.809 (95% CI 0.726–0.921; р<0.0001). Lack of copeptin, NT-proBNP and sST2 concentrations decrease below 28.31pmol/L, 1696 pg/ml and 37.8 ng/ml, respectively, was associated with the highest risk of CV events (HR 5.14 [95% CI (2.204–1198), p<0.0001]; HR 4.41 [95% CI 1.41–9.624], p<0.0001; and HR 6.755 [95% CI 3.026–15.082], p<0.0001, respectively). Value of sST2 at discharge were the most significant predictor of CV events in long-term follow-up combined with standard clinical model (including NT-proBNP) (β=0.59, p<0.0001; AUC=0.843 [ (0.761–0.925), p<0.0001]). Adding copeptin values decreased model significance. Pts without CV events in the study had sST2, copeptin and NT-proBNP levels below 37.8 ng/ml, 28.31 pmol/L and 1696 pg/ml, respectively, after 3, 6, and 12 months of follow-up. Conclusion. Compared with copeptin, sST2 is more powerful predictor of death/hospitalization due to HF during 1 year follow-up after ADHF. Values of soluble ST2-receptor ≥37.8 ng/ml, copeptin ≥28.31pmol/L, and NT-proBNP over 1696 pg/ml at discharge from hospital reflect adverse prognosis in pts with ADHF. Serial copeptin, sST2 and NT-proBNP concentration determination after discharge from the hospital indicates the necessity of reduction the levels of these biomarkers below the cut-off values in long-term follow-up period.
  1. Roger V.L., Go A.S., Lloyd-Jones D.M. et al. Executive Summary: Heart Disease and Stroke Statistics-2012 Update. A Report From the American Heart Association. Circulation 2012;125:188–197.
  2. Heidenreich P.A., Albert N.M., Allen L.A. et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail 2013;6 (3):606–619.
  3. Dickstein K., Cohen-Solal A., Filippatos G. et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008;29 (19):2388–2442.
  4. Fomin I. V., Belenkov Ju. N., Mareev V. Ju. et al. Chronic heart failure prevalence in European part of Russian Federation – results of JePOHA-CHF. Russian Heart Failure Journal 2006;7 (1):4–7. Russian (Фомин И. В., Беленков Ю. Н., Мареев В. Ю. и др. Распространенность хронической сердечной недостаточности в Европейской части Российской Федерации – данные ЭПОХА–ХСН. Сердечная недостаточность 2006;7 (1):4–7.)
  5. Blecker S., Paul M., Taksler G. et al. Heart failure – associated hospitalizations in the United States. J Am Coll Cardiol 2013;61 (12):1259–1267.
  6. Roger V.L., Weston S.A., Redfield M.M. et al. Trends in heart failure incidence and survival in a community-based population. JAMA 2004;292 (3):344–50.
  7. Levy D., Kenchaiah S., Larson M.G. et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med 2002;347 (18):1397–1402.
  8. Maggioni A.P., Dahlström U., Filippatos G. et al. EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail 2013;15 (7):808–817.
  9. Harjola V.P., Follath F., Nieminen M.S. et al. Characteristics, outcomes, and predictors of mortality at 3 months and 1 year in patients hospitalized for acute heart failure. Eur J Heart Fail 2010;12 (3):239–248.
  10. Maggioni A., Dahlstrom U., Filippatos G. et al. EURObservational Research Programme: the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail 2010;12:1076–1084.
  11. Krumholz H.M., Merrill A.R., Schone E.M. et al. Patterns of hospital performance in acute myocardial infarction and heart failure 30-day mortality and readmission. Circ Cardiovasc Qual Outcomes 2009;5:407–413.
  12. Bouvy M.L., Heerdink E.R., Leufkens H.G., Hoes A.W. Predicting mortality in patients with heart failure: a pragmatic approach. Heart 2003;89:605–609.
  13. Levy W.C. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation 2006;113:1424–1433.
  14. Pocock S.J., Wang D., Pfeffer M.A. et al. Predictors of mortality and morbidity in patients with chronic heart failure. Eur Heart J 2006;27:65–75.
  15. Klemenz R., Hoffmann S., Werenskiold A.K. Serum- and onco-proteinmediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen. Proc Natl Acad Sci USA 1989;86:5708–5712.
  16. Davide Bolignano D., Aderville Cabassi A., Enrico Fiaccadori E. et al. Copeptin (CTproAVP), a new tool for understanding the role of vasopressin in pathophysiology. Clin Chem Lab Med 2014;52 (10):1447–1456.
  17. Ky B., French B., Mccloskey K. et al. High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail 2011;4:180–187.
  18. Bayes-Genis A., de Antonio M., Vila J. et al. Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart failure risk stratification: ST2 versus galectin-3. J Am Coll Cardiol 2014;63:158–166.
  19. Pascual-Figal D.A., Ordoñez-Llanos J., Tornel P.L. et al; MUSIC Investigators. Soluble ST2 for predicting sudden cardiac death in patients with chronic heart failure and left ventricular systoloic dysfunction. J Am Coll Cardiol 2009;54:2174–2179.
  20. Felker G.M., Fiuzat M., Thompson V. et al. Soluble ST2 in ambulatory patients with heart failure: association with functional capacity and long-term outcomes. Circ Heart Fail 2013;6:1172–1179.
  21. Gegenhuber A., Struck J., Dieplinger B. et al. Comparative Evaluation of B-Type Natriuretic Peptide, Mid-Regional Pro-A-type Natriuretic Peptide, Mid-Regional Pro-Adrenomedullin, and Copeptin to Predict 1-Year Mortality in Patients With Acute Destabilized Heart Failure. J Cardiac Fail 2007;13:42–49.
  22. Balling L., Kistorp C., Schou M. et al. Plasma Copeptin Levels and Prediction of Outcome in Heart Failure Outpatients: Relation to Hyponatremia and Loop Diuretic Doses. J Cardiac Fail 2012;18:351–358.
  23. Miller W.L., Grill D.E., Struck J., Jaffe A.S. Association of Hyponatremia and Elevated Copeptin With Death and Need for Transplantation in Ambulatory Patients With Chronic Heart Failure. Am J Cardiol 2013;111:880–885.
  24. Pozsonyi Z., Förhecz Z., Gombos T. et al. Copeptin (C-terminal pro ArginineVasopressin) is an Independent Long-Term Prognostic Marker in Heart Failure with Reduced Ejection Fraction. Heart, Lung and Circulation 2015;24:359–367.
  25. Сlinical guidelines for the diagnosis and treatment of chronic and acute heart failure. Kardiologicheskij Vestnik 2016;2:3–33. Russian (Клинические рекомендации по диагностике и лечению хронической и острой сердечной недостаточности. Кардиологический вестник 2016;2:3–33.)
  26. National clinical guidelines (OSSN, RKO, RNMOT) on diagnostics and treatment of chronic heart failure (4th edition). Russian Heart Failure Journal 2013;81 (7):379–472. Russian (Национальные рекомендации ОССН, РКО и РНМОТ по диагностике и лечению ХСН (четвертый пересмотр). Журнал Сердечная Недостаточность 2013;81 (7):379–472.)
  27. 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):147–239.
  28. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016;37:2129–2200.
  29. Januzzi J., van Kimmenade R., Lainchbury J. et al. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study. Eur Heart J 2006;27:330–337.
  30. Luchner A., Behrens G., Stritzke J. et al. Long-term pattern of brain natriuretic peptide and N-terminal pro brain natriuretic peptide and its determinants in the general population: contribution of age, gender, and cardiac and extra-cardiac factors. Eur J Heart Fail 2013;15:859–867.
  31. Wang T.J., Larson M.G., Levy D. et al. Impact of obesity on plasma natriuretic peptide levels. Circulation 2004;109:594–600.
  32. Anwaruddin S., Lloyd-Jones D.M., Baggish A. et al. Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study. JACC 2006;47:91–97.
  33. Wu A.H. B., Smith A.C., Mather J.F. et al. Biological variation for NT-pro and B-type natriuretic peptides and implications for therapeutic monitoring of patients with congestive heart failure. Am J Cardiol 2003;92:628–631.
  34. Skvortsov A.A., Protasov V.N., Narusov O.Yu. et al. Supression of tumorogenicity 2 increases opportunities in patients long-term risk stratification after acute heart failure decompensation. Kardiologiуa 2017;57 (1):48–58. DOI: http://dx.doi.org/10.18565/cardio.2017.1.48–58. Russian (Скворцов А. А., Протасов В. Н., Нарусов О. Ю., и др. Определение концентрации растворимого рецептора подавления туморогенности 2-го типа расширяет возможности в стратификации риска больных после перенесенной декомпенсации хронической сердечной недостаточности. Кардиология 2017;57 (1):48–58).
  35. Kalra P.R., Anker S.T. D., Coats J.S. Water and sodium regulation in chronic heart failure: the role of natriuretic peptides and vasopressin. Cardiovasc Res 2001;51:495–509.
  36. Chatterjee K. Neurohormonal activation in congestive heart failure and the role of vasopressin. Am J Cardiol 2005;95 Suppl:8B – 13B.
  37. Szinnai G., Morgenthaler N.G., Berneis K. et al. Changes in plasma copeptin, the c-terminal portion of arginine vasopressin during water deprivation and excess in healthy subjects. J Clin Endocrinol Metab 2007;92 (10):3973–3978.
  38. Morgenthaler N.G., Struck J., Jochberger S., Dünser M.W. Copeptin: clinical use of a new biomarker. Trends Endocrinol Metab 2008;19 (2):43–49.
  39. Voors A.A., von Haehling S., Anker S.D. et al. OPTIMAAL Investigators. C-terminal provasopressin (copeptin) is a strong prognostic marker in patients with heart failure after an acute myocardial infarction: results from the OPTIMAAL study. Eur Heart J 2009;30 (10):1187–1194.
  40. Zhang P., Wu X., Li G. et al. Prognostic role of copeptin with all-cause mortality after heart failure: a systematic review and meta-analysis Therapeutics and Clinical Risk Management 2017;13:49–58.
  41. Masson S., Latini R., Carbonieri E. et al. The predictive value of stable precursor fragments of vasoactive peptides in patients with chronic heart failure: data from the GISSI-heart failure (GISSI-HF) trial. Eur J Heart Fail 2010; 2:338–347. doi:10.1093/eur-jhf/hfp206
  42. Herrero-Puente P., Prieto-García B., García-García M. et al. Predictive capacity of a multimarker strategy to determine short-term mortality in patients attending a hospital emergency Department for acute heart failure. BIO-EAHFE study. Clinica Chimica Acta 2017;466:22–30.
  43. Maisel A., Xue Y., Shah K. et al. Increased 90-day mortality in patients with acute heart failure with elevated copeptin: secondary results from the Biomarkers in Acute Heart Failure (BACH) study. Circ Heart Fail 2011;4 (5):613–620.
  44. Peacock W.F., Nowak R., Christenson R. et al. Short-term mortality risk in emergency department acute heart failure. Acad Emerg Med 2011;18 (9):947–958.
  45. Weinberg E.O., Shimpo M., De Keulenaer G.W. et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation 2002;106:2961–2966.
  46. Chackerian A.A., Oldham E.R., Murphy E.E. et al. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex. J Immunol 2007;179:2551–2555.
  47. Sanada S., Hakuno D., Higgins L.J. et al. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest 2007;117:1538–1549.
  48. Schmitz J., Owyang A., Oldham E. 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;23:479–490.
  49. Deiplinger B., Gegenhuber A., Kaar G. et al. Prognostic value of established and novel biomarkers in patients with shortness of breath attending an emergency department. Clin Biochem 2010;43:714–719.
  50. Jackson C., Haig C., Welsh P. et al. The incremental prognostic and clinical value of multiple novel biomarkers in heart failure. Eur J Heart Fail 2016;18:1491–1498.
  51. Finley J.J., Konstam M.A., Udelson J.E. Arginine vasopressin antagonists for the treatment of heart failure and hyponatremia. Circulation 2008;118:410–421.
  52. Neuhold S., Huelsmann M., Strunk G. et al. Comparison of Copeptin, B-Type Natriuretic Peptide, and Amino-Terminal Pro-B-Type Natriuretic Peptide in Patients With Chronic Heart Failure. J Am Coll Cardiol 2008;52:266–272.
  53. Anand I.S., Rector T.S., Kuskowski M. et al. Prognostic value of soluble ST2 in the Valsartan Heart Failure Trial. Circ Heart Fail 2014;7:418–426.
  54. Januzzi J.L., Mebazaa A., DiSomma S. ST2 and Prognosis in Acutely Decompensated Heart Failure: The International ST2 Consensus Panel. Am J Cardiol 2015; (suppl): 1A–6A.
Skvortsov A. A., Protasov V. N., Narusov O. Yu., Koshkina D. E., Osmolovskaya Yu. F., Kuznetzova T. V., Masenko V. P., Tereschenko S. N. Head to Head Comparison of Suppression of Tumorogenicity 2 and Copeptin Significance for Prognosis of Patients After Acute Heart Failure Decompensation. Kardiologiia. 2017;57(9):20–33.

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