Heart Failure Reviews

, Volume 19, Issue 3, pp 369–381 | Cite as

Clinical use of novel biomarkers in heart failure: towards personalized medicine

  • Daniela Schmitter
  • Gadi Cotter
  • Adriaan A. Voors


Biomarkers play an important role in heart failure. They provide us information about the mechanisms involved in specific types of heart failure and can identify patients at higher risk. Although the majority of biomarker studies in heart failure focus on their prognostic value, the clinical applicability of prognostication in heart failure needs to be established. However, biomarkers can be used for many other purposes. For example, they can help us with the diagnosis of heart failure, and they can be used to select our therapy, leading to personalized tailored therapy. Finally, when biomarkers are causally involved in the disease process, they can even become targets for therapy. The present paper reviews the established and potential value of the novel heart failure biomarkers, mid-regional atrial natriuretic peptide, soluble ST2, growth differentiation factor 15, galectin-3, renal tubular damage markers, and microRNAs. Their potential clinical value will be discussed and compared with the reference markers, the natriuretic peptides.


Heart failure Biomarkers Personalized medicine Soluble ST2 Galectin-3 MicroRNAs 



Dr. Voors is clinical established investigator of the Dutch Heart Foundation (2006T37), he is supported by a grant from the Dutch Heart Foundation entitled: “Approaching Heart Failure by Translational Research of RNA mechanisms” (ARENA), and he is project leader of a project funded by the European Commission (FP7-242209-BIOSTAT-CHF), entitled: “a systems BIOlogy Study to TAilered Treatment in Chronic Heart Failure (BIOSTAT-CHF)”.

Conflict of interest



  1. 1.
    Felker GM, Hasselblad V, Hernandez AF, O’Connor CM (2009 Sep) Biomarker-guided therapy in chronic heart failure: a meta-analysis of randomized controlled trials. Am Heart J 158(3):422–430PubMedCrossRefGoogle Scholar
  2. 2.
    McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A (2012) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Eur J Heart Fail 14:803–892PubMedCrossRefGoogle Scholar
  3. 3.
    Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA (2002) Breathing Not Properly Multinational Study Investigators. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347:161–167PubMedCrossRefGoogle Scholar
  4. 4.
    Mueller C, Scholer A, Laule-Kilian K, Martina B, Schindler C, Buser P, Pfisterer M, Perruchoud AP (2004) Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. N Engl J Med 350:647–654PubMedCrossRefGoogle Scholar
  5. 5.
    Böhm M, Voors AA, Ketelslegers JM, Schirmer SH, Turgonyi E, Bramlage P, Zannad F (2011) Biomarkers: optimizing treatment guidance in heart failure. Clin Res Cardiol 100:973–981PubMedCrossRefGoogle Scholar
  6. 6.
    Gullestad L, Ueland T, Kjekshus J, Nymo SH, Hulthe J, Muntendam P, Adourian A, Böhm M, van Veldhuisen DJ, Komajda M, Cleland JG, Wikstrand J, McMurray JJ, Aukrust P (2012) CORONA Study Group. Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Eur Heart J 33:2290–2296PubMedCrossRefGoogle Scholar
  7. 7.
    O’Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, Heizer GM, Komajda M, Massie BM, McMurray JJ, Nieminen MS, Reist CJ, Rouleau JL, Swedberg K, Adams KF Jr, Anker SD, Atar D, Battler A, Botero R, Bohidar NR, Butler J, Clausell N, Corbalán R, Costanzo MR, Dahlstrom U, Deckelbaum LI, Diaz R, Dunlap ME, Ezekowitz JA, Feldman D, Felker GM, Fonarow GC, Gennevois D, Gottlieb SS, Hill JA, Hollander JE, Howlett JG, Hudson MP, Kociol RD, Krum H, Laucevicius A, Levy WC, Méndez GF, Metra M, Mittal S, Oh BH, Pereira NL, Ponikowski P, Tang WH, Tanomsup S, Teerlink JR, Triposkiadis F, Troughton RW, Voors AA, Whellan DJ, Zannad F, Califf RM (2011) Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med 365:32–34PubMedCrossRefGoogle Scholar
  8. 8.
    von Haehling S, Jankowska EA, Morgenthaler NG, Vassanelli C, Zanolla L, Rozentryt P, Filippatos GS, Doehner W, Koehler F, Papassotiriou J, Kremastinos DT, Banasiak W, Struck J, Ponikowski P, Bergmann A, Anker SD (2007) Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in predicting survival in patients with chronic heart failure. J Am Coll Cardiol 50:1973–1980CrossRefGoogle Scholar
  9. 9.
    Gegenhuber A, Struck J, Dieplinger B, Poelz W, Pacher R, Morgenthaler NG, Bergmann A, Haltmayer M, Mueller T (2007) 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 Card Fail 13:42–49PubMedCrossRefGoogle Scholar
  10. 10.
    Moertl D, Berger R, Struck J, Gleiss A, Hammer A, Morgenthaler NG, Bergmann A, Huelsmann M, Pacher R (2009) Comparison of midregional pro-atrial and B-type natriuretic peptides in chronic heart failure: influencing factors, detection of left ventricular systolic dysfunction, and prediction of death. J Am Coll Cardiol 53:1783–1790PubMedCrossRefGoogle Scholar
  11. 11.
    Masson S, Latini R, Carbonieri E, Moretti L, Rossi MG, Ciricugno S, Milani V, Marchioli R, Struck J, Bergmann A, Maggioni AP, Tognoni G, Tavazzi L; GISSI-HF Investigators (2010) 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 12:338–347Google Scholar
  12. 12.
    Miller WL, Hartman KA, Grill DE, Struck J, Bergmann A, Jaffe AS (2012) Serial measurements of midregion proANP and copeptin in ambulatory patients with heart failure: incremental prognostic value of novel biomarkers in heart failure. Heart 98:389–394PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Maisel A, Mueller C, Nowak R, Peacock WF, Landsberg JW, Ponikowski P, Mockel M, Hogan C, Wu AH, Richards M, Clopton P, Filippatos GS, Di Somma S, Anand I, Ng L, Daniels LB, Neath SX, Christenson R, Potocki M, McCord J, Terracciano G, Kremastinos D, Hartmann O, von Haehling S, Bergmann A, Morgenthaler NG, Anker SD (2010) Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. J Am Coll Cardiol 55:2062–2076PubMedCrossRefGoogle Scholar
  14. 14.
    Gegenhuber A, Struck J, Poelz W, Pacher R, Morgenthaler NG, Bergmann A, Haltmayer M, Mueller T (2006) Midregional pro-A-type natriuretic peptide measurements for diagnosis of acute destabilized heart failure in short-of-breath patients: comparison with B-type natriuretic peptide (BNP) and amino-terminal proBNP. Clin Chem 52:827–831PubMedCrossRefGoogle Scholar
  15. 15.
    Dieplinger B, Gegenhuber A, Haltmayer M, Mueller T (2009) Evaluation of novel biomarkers for the diagnosis of acute destabilised heart failure in patients with shortness of breath. Heart 95:1508–1513PubMedCrossRefGoogle Scholar
  16. 16.
    Cayrol C, Girard JP (2009) The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. Proc Natl Acad Sci USA 106:9021–9026PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Zhang HF, Xie SL, Chen YX, Mai JT, Wang JF, Zhu WL, Zhu LG (2012) Altered serum levels of IL-33 in patients with advanced systolic chronic heart failure: correlation with oxidative stress. J Transl Med 10:120PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Januzzi JL Jr, Peacock WF, Maisel AS, Chae CU, Jesse RL, Baggish AL, O’Donoghue M, Sakhuja R, Chen AA, van Kimmenade RR, Lewandrowski KB, Lloyd-Jones DM, Wu AH (2007) 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 50:607–613PubMedCrossRefGoogle Scholar
  19. 19.
    Weinberg EO, Shimpo M, Hurwitz S, Tominaga S, Rouleau JL, Lee RT (2003) Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation 107:721–726PubMedCrossRefGoogle Scholar
  20. 20.
    Mueller T, Dieplinger B, Gegenhuber A, Poelz W, Pacher R, Haltmayer M (2008) Increased plasma concentrations of soluble ST2 are predictive for 1-year mortality in patients with acute destabilized heart failure. Clin Chem 54:752–756PubMedCrossRefGoogle Scholar
  21. 21.
    Pascual-Figal DA, Ordoñez-Llanos J, Tornel PL, Vázquez R, Puig T, Valdés M, Cinca J, de Luna AB, Bayes-Genis A, MUSIC Investigators (2009) Soluble ST2 for predicting sudden cardiac death in patients with chronic heart failure and left ventricular systolic dysfunction. J Am Coll Cardiol 54:2174–2179PubMedCrossRefGoogle Scholar
  22. 22.
    Pascual-Figal DA, Manzano-Fernández S, Boronat M, Casas T, Garrido IP, Bonaque JC, Pastor-Perez F, Valdés M, Januzzi JL (2011) Soluble ST2, high-sensitivity troponin T- and N-terminal pro-B-type natriuretic peptide: complementary role for risk stratification in acutely decompensated heart failure. Eur J Heart Fail 13:718–725PubMedCrossRefGoogle Scholar
  23. 23.
    Broch K, Ueland T, Nymo SH, Kjekshus J, Hulthe J, Muntendam P, McMurray JJ, Wikstrand J, Cleland JG, Aukrust P, Gullestad L (2012) Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology. Eur J Heart Fail 14:268–277PubMedCrossRefGoogle Scholar
  24. 24.
    Bayes-Genis A, de Antonio M, Galán A, Sanz H, Urrutia A, Cabanes R, Cano L, González B, Díez C, Pascual T, Elosúa R, Lupón J (2012) Combined use of high-sensitivity ST2 and NTproBNP to improve the prediction of death in heart failure. Eur J Heart Fail 14:32–38PubMedCrossRefGoogle Scholar
  25. 25.
    Boisot S, Beede J, Isakson S, Chiu A, Clopton P, Januzzi J, Maisel AS, Fitzgerald RL (2008) Serial sampling of ST2 predicts 90-day mortality following destabilized heart failure. J Card Fail 14:732–738PubMedCrossRefGoogle Scholar
  26. 26.
    Aldous SJ, Richards AM, Troughton R, Than M (2012) 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 18:304–310PubMedCrossRefGoogle Scholar
  27. 27.
    Santhanakrishnan R, Chong JP, Ng TP, Ling LH, Sim D, Toh G, Leong K, Shuan D, Yeo P, Ong HY, Jaufeerally F, Wong R, Chai P, Low AF, Richards AM, Lam CS (2012) Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N-terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction. Eur J Heart Fail 14:1338–1347PubMedCrossRefGoogle Scholar
  28. 28.
    Kempf T, von Haehling S, Peter T, Allhoff T, Cicoira M, Doehner W, Ponikowski P, Filippatos GS, Rozentryt P, Drexler H, Anker SD, Wollert KC (2007) Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol 50:1054–1060PubMedCrossRefGoogle Scholar
  29. 29.
    Wang TJ, Wollert KC, Larson MG, Coglianese E, McCabe EL, Cheng S, Ho JE, Fradley MG, Ghorbani A, Xanthakis V, Kempf T, Benjamin EJ, Levy D, Vasan RS, Januzzi JL (2012) Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study. Circulation 126:1596–1604PubMedCrossRefGoogle Scholar
  30. 30.
    Anand IS, Kempf T, Rector TS, Tapken H, Allhoff T, Jantzen F, Kuskowski M, Cohn JN, Drexler H, Wollert KC (2010) Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial. Circulation 122:1387–1395PubMedCrossRefGoogle Scholar
  31. 31.
    Baessler A, Strack C, Rousseva E, Wagner F, Bruxmeier J, Schmiedel M, Riegger G, Lahmann C, Loew T, Schmitz G, Fischer M (2012) Growth-differentiation factor-15 improves reclassification for the diagnosis of heart failure with normal ejection fraction in morbid obesity. Eur J Heart Fail 14:1240–1248PubMedCrossRefGoogle Scholar
  32. 32.
    Stahrenberg R, Edelmann F, Mende M, Kockskämper A, Düngen HD, Lüers C, Binder L, Herrmann-Lingen C, Gelbrich G, Hasenfuss G, Pieske B, Wachter R (2010) The novel biomarker growth differentiation factor 15 in heart failure with normal ejection fraction. Eur J Heart Fail 12:1309–1316PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ (2009) Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail 11:811–817PubMedCrossRefGoogle Scholar
  34. 34.
    van Kimmenade RR, Januzzi JL Jr, Ellinor PT, Sharma UC, Bakker JA, Low AF, Martinez A, Crijns HJ, MacRae CA, Menheere PP, Pinto YM (2006) 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 48:1217–1224PubMedCrossRefGoogle Scholar
  35. 35.
    Shah RV, Chen-Tournoux AA, Picard MH, van Kimmenade RR, Januzzi JL (2010) Galectin-3, cardiac structure and function, and long-term mortality in patients with acutely decompensated heart failure. Eur J Heart Fail 12:826–832PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Fermann GJ, Lindsell CJ, Storrow AB, Hart K, Sperling M, Roll S, Weintraub NL, Miller KF, Maron DJ, Naftilan AJ, McPherson JA, Sawyer DB, Christenson R, Collins SP (2012 Dec) Galectin 3 complements BNP in risk stratification in acute heart failure. Biomarkers 17(8):706–713PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Lok DJ, Van Der Meer P, de la Porte PW, Lipsic E, Van Wijngaarden J, Hillege HL, van Veldhuisen DJ (2010) Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study. Clin Res Cardiol 99:323–328PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    de Boer RA, Lok DJ, Jaarsma T, van der Meer P, Voors AA, Hillege HL, van Veldhuisen DJ (2011) Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction. Ann Med 43:60–68PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Tang WH, Shrestha K, Shao Z, Borowski AG, Troughton RW, Thomas JD, Klein AL (2011) Usefulness of plasma galectin-3 levels in systolic heart failure to predict renal insufficiency and survival. Am J Cardiol 108:385–390PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Ueland T, Aukrust P, Broch K, Aakhus S, Skårdal R, Muntendam P, Gullestad L (2011) Galectin-3 in heart failure: high levels are associated with all-cause mortality. Int J Cardiol 150:361–364PubMedCrossRefGoogle Scholar
  41. 41.
    Lopez-Andrès N, Rossignol P, Iraqi W, Fay R, Nuée J, Ghio S, Cleland JG, Zannad F, Lacolley P (2012) Association of galectin-3 and fibrosis markers with long-term cardiovascular outcomes in patients with heart failure, left ventricular dysfunction, and dyssynchrony: insights from the CARE-HF (Cardiac Resynchronization in Heart Failure) trial. Eur J Heart Fail 14:74–81PubMedCrossRefGoogle Scholar
  42. 42.
    Gullestad L, Ueland T, Kjekshus J, Nymo SH, Hulthe J, Muntendam P, McMurray JJ, Wikstrand J, Aukrust P (2012) The predictive value of galectin-3 for mortality and cardiovascular events in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Am Heart J 164:878–883PubMedCrossRefGoogle Scholar
  43. 43.
    Felker GM, Fiuzat M, Shaw LK, Clare R, Whellan DJ, Bettari L, Shirolkar SC, Donahue M, Kitzman DW, Zannad F, Piña IL, O’Connor CM (2012) Galectin-3 in ambulatory patients with heart failure: results from the HF-ACTION study. Circ Heart Fail 5:72–78PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Sherwi N, Merali S, Wong K (2012) Personalizing biomarker strategies in heart failure with galectin-3. Future Cardiol. 8:885–894PubMedCrossRefGoogle Scholar
  45. 45.
    Laurent C, Maria M, Pascal R, Victoria C, Ernesto MM, de Boer RA, Françoise P, Patrick L, Faiez Z, Patrick R, Natalia LA (2012) Galectin-3 mediates aldosterone-induced vascular fibrosis. Arterioscler Thromb Vasc Biol 1 Nov 2012 [Epub ahead of print]Google Scholar
  46. 46.
    Henderson NC, Mackinnon AC, Farnworth SL, Poirier F, Russo FP, Iredale JP, Haslett C, Simpson KJ, Sethi T (2006) Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci USA 103:5060–5065PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Ho JE, Liu C, Lyass A, Courchesne P, Pencina MJ, Vasan RS, Larson MG, Levy D (2012) Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community. J Am Coll Cardiol 60:1249–1256PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Metra M, Cotter G, Gheorghiade M, Dei Cas L, Voors AA (2012) The role of the kidney in heart failure. Eur Heart J 33:2135–2142PubMedCrossRefGoogle Scholar
  49. 49.
    Brandimarte F, Vaduganathan M, Mureddu GF, Cacciatore G, Sabbah HN, Fonarow GC, Goldsmith SR, Butler J, Fedele F, Gheorghiade M (2012) Prognostic implications of renal dysfunction in patients hospitalized with heart failure: data from the last decade of clinical investigations. Heart Fail Rev 10 May 2012 [Epub ahead of print]Google Scholar
  50. 50.
    Cleland JG, Carubelli V, Castiello T, Yassin A, Pellicori P, Antony R (2012) Renal dysfunction in acute and chronic heart failure: prevalence, incidence and prognosis. Heart Fail Rev 17:133–149PubMedCrossRefGoogle Scholar
  51. 51.
    Damman K, Voors AA, Navis G, van Veldhuisen DJ, Hillege HL (2012) Current and novel renal biomarkers in heart failure. Heart Fail Rev 17:241–250PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Valente MA, Damman K, Dunselman PH, Hillege HL, Voors AA (2012) Urinary proteins in heart failure. Prog Cardiovasc Dis 55:44–55PubMedCrossRefGoogle Scholar
  53. 53.
    Damman K, Masson S, Hillege HL, Maggioni AP, Voors AA, Opasich C, van Veldhuisen DJ, Montagna L, Cosmi F, Tognoni G, Tavazzi L, Latini R (2011) Clinical outcome of renal tubular damage in chronic heart failure. Eur Heart J 32:2705–2712PubMedCrossRefGoogle Scholar
  54. 54.
    Jungbauer CG, Birner C, Jung B, Buchner S, Lubnow M, von Bary C, Endemann D, Banas B, Mack M, Böger CA, Riegger G, Luchner A (2011) Kidney injury molecule-1 and N-acetyl-β-d-glucosaminidase in chronic heart failure: possible biomarkers of cardiorenal syndrome. Eur J Heart Fail 13:1104–1110PubMedCrossRefGoogle Scholar
  55. 55.
    Damman K, Van Veldhuisen DJ, Navis G, Vaidya VS, Smilde TD, Westenbrink BD, Bonventre JV, Voors AA, Hillege HL (2010) Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate. Heart 96:1297–1302PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Alvelos M, Lourenço P, Dias C, Amorim M, Rema J, Leite AB, Guimarães JT, Almeida P, Bettencourt P (2011) Prognostic value of neutrophil gelatinase-associated lipocalin in acute heart failure. Int J Cardiol [Epub ahead of print]Google Scholar
  57. 57.
    Maisel AS, Mueller C, Fitzgerald R, Brikhan R, Hiestand BC, Iqbal N, Clopton P, van Veldhuisen DJ (2011) Prognostic utility of plasma neutrophil gelatinase-associated lipocalin in patients with acute heart failure: the NGAL EvaLuation Along with B-type NaTriuretic Peptide in acutely decompensated heart failure (GALLANT) trial. Eur J Heart Fail 13:846–851PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Damman K, Ng Kam Chuen MJ, MacFadyen RJ, Lip GY, Gaze D, Collinson PO, Hillege HL, van Oeveren W, Voors AA, van Veldhuisen DJ (2011) Volume status and diuretic therapy in systolic heart failure and the detection of early abnormalities in renal and tubular function. J Am Coll Cardiol 57:2233–2241Google Scholar
  59. 59.
    Aghel A, Shrestha K, Mullens W, Borowski A, Tang WH (2010) Serum neutrophil gelatinase-associated lipocalin (NGAL) in predicting worsening renal function in acute decompensated heart failure. J Card Fail 16:49–54PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365(9466):1231–1238PubMedCrossRefGoogle Scholar
  61. 61.
    Dobre D, Rossignol P, Metra M, Zannad F (2012) Can we prevent or treat renal dysfunction in chronic heart failure? Heart Fail Rev 17:283–290PubMedCrossRefGoogle Scholar
  62. 62.
    Sayed D, Hong C, Chen IY, Lypowy J, Abdellatif M (2007) MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 100(3):416–424PubMedCrossRefGoogle Scholar
  63. 63.
    Matkovich SJ, Wang W, Tu Y, Eschenbacher WH, Dorn LE, Condorelli G, et al (2010) MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts. Circ Res 106(1):166–175Google Scholar
  64. 64.
    Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O (2012) Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail 14:147–154PubMedCrossRefGoogle Scholar
  65. 65.
    Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, Pinto YM (2010) MiR423-5p as a circulating biomarker for heart failure. Circ Res 106:1035–1039PubMedCrossRefGoogle Scholar
  66. 66.
    Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N (2011) Assessment of plasma mirnas in congestive heart failure. Circ J 75:336–340PubMedCrossRefGoogle Scholar
  67. 67.
    Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, Wagner DR, Staessen JA, Heymans S, Schroen B (2010) Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 3:499–506PubMedCrossRefGoogle Scholar
  68. 68.
    Matkovich SJ, Van Booven DJ, Youker KA, Torre-Amione G, Diwan A, Eschenbacher WH et al (2009) Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support. Circulation 119(9):1263–1271PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Oliveira-Carvalho V, d. Silva MMF, Guimara˜es GV, Bacal F, Bocchi EA (2012) MicroRNAs: new players in heart failure. Mol Biol Rep [Epub ahead of print]Google Scholar
  70. 70.
    Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438(7068):685–689PubMedCrossRefGoogle Scholar
  71. 71.
    Wang Z (2011) The guideline of the design and validation of MiRNA mimics. Methods Mol Biol 676:211–223PubMedCrossRefGoogle Scholar
  72. 72.
    Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M et al (2008) MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456(7224):980–984PubMedCrossRefGoogle Scholar
  73. 73.
    Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM et al (2011) Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation 124(14):1537–1547PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Suckau L, Fechner H, Chemaly E, Krohn S, Hadri L, Kockskämper J et al (2009) Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation 119(9):1241–1252PubMedCrossRefGoogle Scholar
  75. 75.
    Lindow M, Kauppinen S (2012) Discovering the first microRNA-targeted drug. J Cell Biol 199(3):407–412PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Adachi T, Nakanishi M, Otsuka Y, Nishimura K, Hirokawa G, Goto Y, Nonogi H, Iwai N (2010) Plasma MicroRNA 499 as a biomarker of acute myocardial infarction. Clin Chem 56(7):1183–1185PubMedCrossRefGoogle Scholar
  77. 77.
    Tutarel O, Dangwal S, Bretthauer J, Westhoff-Bleck M, Roentgen P, Anker SD, Bauersachs J, Thum T (2011) Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries. Int J Cardiol [Epub ahead of print]Google Scholar
  78. 78.
    Voellenkle C, van Rooij J, Cappuzello C, Greco S, Arcelli D, Di Vito L, Melillo G, Rigolini R, Costa E, Crea F, Capogrossi MC, Napolitano M, Martelli F (2010) MicroRNA signatures in peripheral blood mononuclear cells of chronic heart failure patients. Physiol Genomics 42(3):420–426PubMedCrossRefGoogle Scholar
  79. 79.
    Nair N, Kumar S, Gongora E, Gupta S (2012) Circulating miRNA as novel markers for diastolic dysfunction. Mol Cell Biochem [Epub ahead of print]Google Scholar
  80. 80.
    Cleland JG, McMurray JJ, Kjekshus J, Cornel JH, Dunselman P, Fonseca C, Hjalmarson A, Korewicki J, Lindberg M, Ranjith N, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J, CORONA Study Group (2009) Controlled Rosuvastatin Multinational Trial in Heart Failure. Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA. J Am Coll Cardiol 54:1850–1859PubMedCrossRefGoogle Scholar
  81. 81.
    Farmakis D, Filippatos G, Parissis J, Kremastinos DT, Gheorghiade M (2009) Hyponatremia in heart failure. Heart Fail Rev 14:59–63PubMedCrossRefGoogle Scholar
  82. 82.
    Preston RA, Materson BJ, Reda DJ, Williams DW, Hamburger RJ, Cushman WC, Anderson RJ (1998) Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. JAMA 280:1168–1172PubMedCrossRefGoogle Scholar
  83. 83.
    van Deursen VM, Damman K, van der Meer P, Wijkstra PJ, Luijckx GJ, van Beek A, van Veldhuisen DJ, Voors AA (2012) Co-morbidities in heart failure. Heart Fail Rev 25 Dec 2012 [Epub ahead of print]Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Daniela Schmitter
    • 1
  • Gadi Cotter
    • 2
  • Adriaan A. Voors
    • 3
  1. 1.Momentum Research, Inc.AllschwilSwitzerland
  2. 2.Momentum Research, Inc.DurhamUSA
  3. 3.Department of Cardiology, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands

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