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01-10-2015 | Biomarkers of Heart Failure (W.H.W. Tang, Section Editor)

The Current and Potential Clinical Relevance of Heart Failure Biomarkers

Authors: Parul U. Gandhi, Jeffrey M. Testani, Tariq Ahmad

Published in: Current Heart Failure Reports | Issue 5/2015

Abstract

Heart failure is a growing epidemic, and our understanding of the intricacies of its pathophysiology continues to evolve. Over the last decade, biomarkers of heart failure have been extensively investigated, particularly for diagnosis and risk stratification. While the natriuretic peptides remain the gold standard heart failure biomarker, they are plagued by their non-specific nature; furthermore, the strategy of natriuretic peptide-guided care remains elusive. Multiple candidate markers indicative of other physiologic aspects of heart failure have been identified and studied, including soluble ST2, galectin-3, and high-sensitivity cardiac troponins. Each of these biomarkers has the potential to provide unique therapeutically relevant information. Ultimately, a multi-marker approach may be applied to improve care of patients with heart failure. Definitive clinical trials and the use of advanced statistical analytic techniques are needed to truly determine the optimal strategy of biomarker-assisted diagnosis, prognostication, and management of patients who suffer from this devastating condition.

Katz AM. The "modern" view of heart failure: how did we get here? Circ Heart Fail. 2008;1:63–71.CrossRefPubMed

Mozaffarian D et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–322. doi:10.1161/CIR.0000000000000152.CrossRefPubMed

Yancy CW et al. 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. Circulation. 2013;128:e240–327. doi:10.1161/CIR.0b013e31829e8776.CrossRefPubMed

4.••

Ahmad T et al. Charting a roadmap for heart failure biomarker studies. JACC Heart Fail. 2014;2:477–88. doi:10.1016/j.jchf.2014.02.005. This reference outlines the current state of biomarker research and provides a guide for how to design trials to appropriately study biomarkers going forward. CrossRefPubMed

Morrow DA, de Lemos JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation. 2007;115:949–52. doi:10.1161/CIRCULATIONAHA.106.683110.CrossRefPubMed

6.•

van Kimmenade RR, Januzzi Jr JL. Emerging biomarkers in heart failure. Clin Chem. 2012;58:127–38. doi:10.1373/clinchem.2011.165720. This paper delineates the criteria for a useful biomarker in heart failure and describes some important candidate markers. CrossRefPubMed

Munagala VK, Burnett Jr JC, Redfield MM. The natriuretic peptides in cardiovascular medicine. Curr Probl Cardiol. 2004;29:707–69. doi:10.1016/j.cpcardiol.2004.07.002.CrossRefPubMed

Januzzi Jr JL et al. The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol. 2005;95:948–54. doi:10.1016/j.amjcard.2004.12.032.CrossRefPubMed

Maisel AS et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161–7. doi:10.1056/NEJMoa020233.CrossRefPubMed

10.

Costello-Boerrigter LC et al. Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction. J Am Coll Cardiol. 2006;47:345–53. doi:10.1016/j.jacc.2005.09.025.PubMedCentralCrossRefPubMed

11.

Weinberg EO et al. Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation. 2003;107:721–6.CrossRefPubMed

12.

Sanada S et al. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest. 2007;117:1538–49.PubMedCentralCrossRefPubMed

13.

Weinberg EO et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation. 2002;106:2961–6.PubMedCentralCrossRefPubMed

14.

Seki K et al. Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail. 2009;2:684–91.CrossRefPubMed

15.

Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov. 2008;7:827–40. doi:10.1038/nrd2660.PubMedCentralCrossRefPubMed

16.

Januzzi Jr JL 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;50:607–13.CrossRefPubMed

17.

Ky B et al. High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail. 2011;4:180–7. doi:10.1161/CIRCHEARTFAILURE.110.958223.PubMedCentralCrossRefPubMed

18.

Gaggin HK et al. Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highly-sensitive troponin T measurements in patients with chronic heart failure. JACC Heart Fail. 2014;2:65–72. doi:10.1016/j.jchf.2013.10.005.CrossRefPubMed

19.

Jougasaki M, Burnett Jr JC. Adrenomedullin: potential in physiology and pathophysiology. Life Sci. 2000;66:855–72.CrossRefPubMed

20.

Morgenthaler NG, Struck J, Alonso C, Bergmann A. Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay. Clin Chem. 2005;51:1823–9. doi:10.1373/clinchem.2005.051110.CrossRefPubMed

21.

Peacock WF et al. Short-term mortality risk in emergency department acute heart failure. Acad Emerg Med. 2011;18:947–58. doi:10.1111/j.1553-2712.2011.01150.x.CrossRefPubMed

22.

von Haehling S et al. Mid-regional pro-adrenomedullin as a novel predictor of mortality in patients with chronic heart failure. Eur J Heart Fail. 2010;12:484–91. doi:10.1093/eurjhf/hfq031.CrossRef

23.

Ahmad T, Felker GM. Subcutaneous B-type natriuretic peptide for treatment of heart failure: a dying therapy reborn? J Am Coll Cardiol. 2012;60:2313–5. doi:10.1016/j.jacc.2012.08.991.CrossRefPubMed

24.

McMurray JJ et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004. doi:10.1056/NEJMoa1409077.CrossRefPubMed

25.

Vardeny O, Miller R, Solomon SD. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663–70. doi:10.1016/j.jchf.2014.09.001.CrossRefPubMed

26.

Packer M et al. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation. 2015;131:54–61. doi:10.1161/CIRCULATIONAHA.114.013748.CrossRefPubMed

27.

Gaggin HK, Motiwala S, Bhardwaj A, Parks KA, Januzzi Jr JL. Soluble concentrations of the interleukin receptor family member ST2 and beta-blocker therapy in chronic heart failure. Circ Heart Fail. 2013;6:1206–13. doi:10.1161/CIRCHEARTFAILURE.113.000457.CrossRefPubMed

28.

Anand IS, Rector TS, Kuskowski M, Snider J, Cohn JN. Prognostic value of soluble ST2 in the Valsartan Heart Failure Trial. Circ Heart Fail. 2014;7:418–26. doi:10.1161/CIRCHEARTFAILURE.113.001036.CrossRefPubMed

29.

Maisel A et al. Effect of spironolactone on 30-day death and heart failure rehospitalization (from the COACH Study). Am J Cardiol. 2014;114:737–42. doi:10.1016/j.amjcard.2014.05.062.CrossRefPubMed

30.

Peacock WF. Novel biomarkers in acute heart failure: MR-pro-adrenomedullin. Clin Chem Lab Med. 2014;52:1433–5. doi:10.1515/cclm-2014-0222.PubMed

31.••

Braunwald E. Heart failure. JACC Heart Fail. 2013;1:1–20. doi:10.1016/j.jchf.2012.10.002. This paper is an outstanding review of the current state of research and understanding of heart failure. CrossRefPubMed

32.•

Januzzi Jr JL, Filippatos G, Nieminen M, Gheorghiade M. Troponin elevation in patients with heart failure: on behalf of the third Universal Definition of Myocardial Infarction Global Task Force: Heart Failure Section. Eur Heart J. 2012;33:2265–71. doi:10.1093/eurheartj/ehs191. This paper explains the use of troponin in heart failure and discusses the various etiologies of troponin release in heart failure. CrossRefPubMed

33.

Peacock WFt et al. Cardiac troponin and outcome in acute heart failure. N Engl J Med. 2008;358:2117–26. doi:10.1056/NEJMoa0706824.CrossRefPubMed

34.

Latini R et al. Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation. 2007;116:1242–9. doi:10.1161/CIRCULATIONAHA.106.655076.CrossRefPubMed

35.

Motiwala SR et al. Concentrations of highly sensitive cardiac troponin-I predict poor cardiovascular outcomes and adverse remodeling in chronic heart failure. J Cardiovasc Transl Res. 2015;8:164–72. doi:10.1007/s12265-015-9618-4.CrossRefPubMed

36.

Metra M et al. Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) development program: correlation with outcomes. J Am Coll Cardiol. 2013;61:196–206. doi:10.1016/j.jacc.2012.11.005.CrossRefPubMed

37.

Anand IS et al. C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation. 2005;112:1428–34. doi:10.1161/CIRCULATIONAHA.104.508465.CrossRefPubMed

38.

Rauchhaus M et al. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation. 2000;102:3060–7.CrossRefPubMed

39.

Chung ES et al. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107:3133–40. doi:10.1161/01.CIR.0000077913.60364.D2.CrossRefPubMed

40.

Mann DL et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation. 2004;109:1594–602. doi:10.1161/01.CIR.0000124490.27666.B2.CrossRefPubMed

41.

Petersen JW, Felker GM. Inflammatory biomarkers in heart failure. Congest Heart Fail. 2006;12:324–8.CrossRefPubMed

42.

Kempf T et al. Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:1054–60.CrossRefPubMed

43.

Anand IS et al. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial. Circulation. 2010;122:1387–95. doi:10.1161/CIRCULATIONAHA.109.928846.CrossRefPubMed

44.

Papaspyridonos M et al. Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction. Arterioscler Thromb Vasc Biol. 2008;28:433–40. doi:10.1161/ATVBAHA.107.159160.CrossRefPubMed

45.

Sharma UC et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004;110:3121–8.CrossRefPubMed

46.

van Kimmenade RR et al. Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure. J Am Coll Cardiol. 2006;48:1217–24.CrossRefPubMed

47.

Felker GM et al. Galectin-3 in ambulatory patients with heart failure: results from the HF-ACTION study. Circ Heart Fail. 2012;5:72–8. doi:10.1161/CIRCHEARTFAILURE.111.963637.PubMedCentralCrossRefPubMed

48.

Gullestad L et al. Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Eur Heart J. 2012;33:2290–6. doi:10.1093/eurheartj/ehs077.CrossRefPubMed

49.

Anand IS et al. Baseline and serial measurements of galectin-3 in patients with heart failure: relationship to prognosis and effect of treatment with valsartan in the Val-HeFT. Eur J Heart Fail. 2013;15:511–8. doi:10.1093/eurjhf/hfs205.CrossRefPubMed

50.

Calvier L et al. Galectin-3 mediates aldosterone-induced vascular fibrosis. Arterioscler Thromb Vasc Biol. 2013;33:67–75. doi:10.1161/ATVBAHA.112.300569.CrossRefPubMed

51.

Fiuzat M et al. Relationship between galectin-3 levels and mineralocorticoid receptor antagonist use in heart failure: analysis from HF-ACTION. J Card Fail. 2014;20:38–44. doi:10.1016/j.cardfail.2013.11.011.PubMedCentralCrossRefPubMed

52.

Gandhi PU et al. Galectin-3 and mineralocorticoid receptor antagonist use in patients with chronic heart failure due to left ventricular systolic dysfunction. Am Heart J. 2015;169:404–411 e403. doi:10.1016/j.ahj.2014.12.012.CrossRefPubMed

53.

Ahmad T et al. Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure. JACC Heart Fail. 2014;2:260–8. doi:10.1016/j.jchf.2013.12.004.PubMedCentralCrossRefPubMed

54.

Yu L et al. Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis. Circ Heart Fail. 2013;6:107–17. doi:10.1161/CIRCHEARTFAILURE.112.971168.CrossRefPubMed

55.

Stead Jr EA. Edema of heart failure. Bull N Y Acad Med. 1948;24:607–14.PubMedCentralPubMed

56.

Damman K, Tang WH, Testani JM, McMurray JJ. Terminology and definition of changes renal function in heart failure. Eur Heart J. 2014;35:3413–6. doi:10.1093/eurheartj/ehu320.CrossRefPubMed

57.•

Damman K, Testani JM. The kidney in heart failure: an update. Eur Heart J. 2015;36:1437–44. doi:10.1093/eurheartj/ehv010. This paper provides a comprehensive overview of the intricate relationship between the heart and kidney in heart failure. CrossRefPubMed

58.

Konstam MA. Renal function and heart failure treatment: when is a loss really a gain? Circ Heart Fail. 2011;4:677–9. doi:10.1161/CIRCHEARTFAILURE.111.964874.CrossRefPubMed

59.

Ahmad T, O'Connor CM. Therapeutic implications of biomarkers in chronic heart failure. Clin Pharmacol Ther. 2013;94:468–79. doi:10.1038/clpt.2013.139.CrossRefPubMed

60.

Brisco MA, Testani JM. Novel renal biomarkers to assess cardiorenal syndrome. Current Heart Fail Rep. 2014;11:485–99. doi:10.1007/s11897-014-0226-4.CrossRef

61.

61 Damman, K., Voors, A. A., Navis, G., van Veldhuisen, D. J. & Hillege, H. L. Current and novel renal biomarkers in heart failure. Heart Fail Rev.

62.

Troughton RW, Richards AM, Nicholls MG. Individualized treatment of heart failure. Intern Med J. 2001;31:138–41.CrossRefPubMed

63.

Troughton R, Michael Felker G, Januzzi Jr JL. Natriuretic peptide-guided heart failure management. Eur Heart J. 2014;35:16–24. doi:10.1093/eurheartj/eht463.CrossRefPubMed

64.

Felker GM et al. Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure. JACC Heart Fail. 2014;2:457–65. doi:10.1016/j.jchf.2014.05.007.CrossRefPubMed

65.

Pitt B et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370:1383–92. doi:10.1056/NEJMoa1313731.CrossRefPubMed

66.

Allen LA. Use of multiple biomarkers in heart failure. Curr Cardiol Rep. 2010;12:230–6. doi:10.1007/s11886-010-0109-6.CrossRefPubMed

67.

Ky B et al. Multiple biomarkers for risk prediction in chronic heart failure. Circ Heart Fail. 2012;5:183–90. doi:10.1161/CIRCHEARTFAILURE.111.965020.PubMedCentralCrossRefPubMed

68.

Krumholz HM. Big data and new knowledge in medicine: the thinking, training, and tools needed for a learning health system. Health Aff. 2014;33:1163–70. doi:10.1377/hlthaff.2014.0053.CrossRef

69.

Januzzi Jr JL, Felker GM. Surfing the biomarker tsunami at JACC: heart failure. JACC Heart Fail. 2013;1:213–5. doi:10.1016/j.jchf.2013.03.007.CrossRefPubMed

Title: The Current and Potential Clinical Relevance of Heart Failure Biomarkers
Authors: Parul U. Gandhi
Jeffrey M. Testani
Tariq Ahmad
Publication date: 01-10-2015
Publisher: Springer US
Published in: Current Heart Failure Reports / Issue 5/2015
Print ISSN: 1546-9530
Electronic ISSN: 1546-9549
DOI: https://doi.org/10.1007/s11897-015-0268-2

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