Heart Failure Reviews

, Volume 15, Issue 4, pp 351–370 | Cite as

Biomarker guided therapy for heart failure: focus on natriuretic peptides

  • Kirkwood F. AdamsJr.
  • G. Michael Felker
  • Ghassan Fraij
  • J. Herbert Patterson
  • Christopher M. O’Connor
Article

Abstract

The management of heart failure remains challenging despite many therapeutic advances. Rigorous clinical trial evidence supports administration of multiple therapies, but utilization of evidence-based treatment remains inconsistent and suboptimal. Disease management programs appear effective, but remain costly and difficult to implement in today’s care system. Another approach involves optimizing therapy based on serial monitoring of cardiac biomarkers. Emerging results suggest that guiding therapy based on serial changes in natriuretic peptides may be an effective strategy. Although pilot work has provided encouraging results, appropriately designed, large-scale, prospective randomized trials are needed to confirm these preliminary findings and definitively establish this therapeutic approach.

Keywords

Biomarker Heart failure Natriuretic peptides Therapeutic monitoring 

References

  1. 1.
    Adams KF, Lindenfeld J, Arnold JMO, Baker DW, Barnard DH, Baughman KL, Boehmer JP, Deedwania P, Dunbar SB, Elkayam U, Gheorghiade M, Howlett JG, Konstam MA, Kronenberg MW, Massie BM, Mehra MR, Miller AB, Moser DK, Patterson JH, Rodeheffer RJ, Sackner-Bernstein J, Silver MA, Starling RC, Stevenson LW, Wagoner LE (2006) Executive summary: HFSA 2006 comprehensive heart failure practice guideline. J Card Fail 12:10–38CrossRefGoogle Scholar
  2. 2.
    Curtis LH, Greiner MA, Hammill BG, Kramer JM, Whellan DJ, Schulman KA, Hernandez AF (2008) Early and long-term outcomes of heart failure in elderly persons, 2001–2005. Arch Intern Med 168:2481–2488CrossRefPubMedGoogle Scholar
  3. 3.
    Lenzen MJ, Boersma E, Scholte op Reimer WJM, Balk AHMM, Komajda M, Swedberg K, Follath F, Jimenez-Navarro M, Simoons ML, Cleland JGF (2005) Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure. Eur Heart J 26:2706–2713CrossRefPubMedGoogle Scholar
  4. 4.
    Lainscak M, Cleland JG, Lenzen MJ, Follath F, Komajda M, Swedberg K (2007) International variations in the treatment and co-morbidity of left ventricular systolic dysfunction: data from the EuroHeart Failure Survey. Eur J Heart Fail 9:292–299CrossRefPubMedGoogle Scholar
  5. 5.
    de Groote P, Isnard R, Assyag P, Clerson P, Ducardonnet A, Galinier M, Jondeau G, Leurs I, Thebaut JF, Komajda M (2007) Is the gap between guidelines and clinical practice in heart failure treatment being filled? Insights from the IMPACT RECO survey. Eur J Heart Fail 9(12):1205–1211CrossRefPubMedGoogle Scholar
  6. 6.
    Kass DA (2009) Rescuing a failing heart: putting on the squeeze. Nat Med 15:24–25CrossRefPubMedGoogle Scholar
  7. 7.
    Anderson ME, Mohler PJ (2009) Rescuing a failing heart: think globally, treat locally. Nat Med 15:25–26CrossRefPubMedGoogle Scholar
  8. 8.
    Peters-Klimm F, Müller-Tasch T, Remppis A, Szecsenyi J, Schellberg D (2008) Improved guideline adherence to pharmacotherapy of chronic systolic heart failure in general practice—results from a cluster-randomized controlled trial of implementation of a clinical practice guideline. J Eval Clin Pract 14:823–829PubMedGoogle Scholar
  9. 9.
    Cleland JG, Louis AA, Rigby AS, Janssens U, Balk AH, TEN-HMS Investigators (2005) Noninvasive home telemonitoring for patients with heart failure at high risk of recurrent admission and death: the Trans-European Network-Home-Care Management System (TEN-HMS) study. J Am Coll Cardiol 45:1654–1664CrossRefPubMedGoogle Scholar
  10. 10.
    Clark RA, Inglis SC, McAlister FA, Cleland JG, Stewart S (2007) Telemonitoring or structured telephone support programmes for patients with chronic heart failure: systematic review and meta-analysis. BMJ 334:942CrossRefPubMedGoogle Scholar
  11. 11.
    Vasan RS (2006) Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation 113:2335–2362CrossRefPubMedGoogle Scholar
  12. 12.
    Tang WH, Francis GS, Morrow DA, Newby LK, Cannon CP, Jesse RL, Storrow AB, Christenson RH, Apple FS, Rayklide J, Wu AH, National Academy of Clinical Biochemistry Laboratory Medicine (2007) National Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: clinical utilization of cardiac biomarker testing in heart failure. Circulation 116:e99–e109CrossRefPubMedGoogle Scholar
  13. 13.
    Braunwald E (2008) Biomarkers in heart failure. N Engl J Med 358:2148–2159CrossRefPubMedGoogle Scholar
  14. 14.
    Maisel A, Mueller C, Adams KF Jr, Anker SD, Aspromonte N, Cleland JGF, Cohen-Solal A, Dahlstrom U, DeMaria A, Di Somma S, Filippatos GS, Fonarow GC, Jourdain P, Komajda M, Liu PP, McDonagh T, McDonald K, Mebazaa A, Nieminen MS, Peacock F, Tubaro M, Valle R, Vanderhyden M, Yancy CW, Zannad F, Braunwald E (2008) State of the art: using natriuretic peptide levels in clinical practice. Eur J Heart Fail 10:824–839CrossRefPubMedGoogle Scholar
  15. 15.
    Mueller C, Breidthardt T, Laule-Kilian K, Christ M, Peruchoud AP (2007) The integration of BNP and NT-pro BNP into clinical medicine. Swiss Med Wkly 137:4–12PubMedGoogle Scholar
  16. 16.
    Daniels LB, Maisel AS (2007) Natriuretic peptides. J Am Coll Cardiol 50:2357–2368CrossRefPubMedGoogle Scholar
  17. 17.
    Rehman SU, Januzzi JL (2008) Natriuretic peptide testing in clinical medicine. Cardiol Rev 16:240–249CrossRefPubMedGoogle Scholar
  18. 18.
    Martinez-Rumayor A, Richards AM, Burnett JC, Januzzi JL Jr (2008) Biology of the natriuretic peptides. Am J Cardiol 101(3A):3–8CrossRefPubMedGoogle Scholar
  19. 19.
    Lee CY, Burnett JC Jr (2007) Natriuretic peptides and therapeutic applications. Heart Fail Rev 12:131–142CrossRefPubMedGoogle Scholar
  20. 20.
    Sutton TM, Stewart RA, Gerber IL, West TM, Richards AM, Yandle TG, Kerr AJ (2003) Plasma natriuretic peptide levels increase with symptoms and severity of mitral regurgitation. J Am Coll Cardiol 41:2280–2287CrossRefPubMedGoogle Scholar
  21. 21.
    Krittayaphong R, Boonyasirinant T, Saiviroonporn P, Thanapiboonpol P, Nakyen S, Udompunturak S (2008) Correlation between NT-pro BNP levels and left ventricular wall stress, sphericity index and extent of myocardial damage: a magnetic resonance imaging study. J Card Fail 14:687–694CrossRefPubMedGoogle Scholar
  22. 22.
    Morrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, Maisel A (2002) Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. J Am Coll Cardiol 39:202–209CrossRefPubMedGoogle Scholar
  23. 23.
    Januzzi JL Jr, Camargo CA, Anwaruddin S, Baggish AL, Chen AA, Krauser DG, Tung R, Cameron R, Nagurney JT, Chae CU, Lloyd-Jones DM, Brown DF, Foran-Melanson S, Sluss PM, Lee-Lewandrowski E, Lewandrowski KB (2005) The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol 95:948–954CrossRefPubMedGoogle Scholar
  24. 24.
    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, Breathing Not Properly Multinational Study Investigators (2002) Rapid measurement of B-Type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347:161–167CrossRefPubMedGoogle Scholar
  25. 25.
    Jaffe AS, Babuin L (2005) Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ 173:1191–1202PubMedGoogle Scholar
  26. 26.
    Peacock WF 4th, De Marco T, Fonarow GC, Diercks D, Wynne J, Apple FS, Wu AH, ADHERE Investigators (2008) Cardiac troponin and outcome in acute heart failure. N Engl J Med 358:2117–2126CrossRefPubMedGoogle Scholar
  27. 27.
    Januzzi JL Jr, Sakhuja R, O’donoghue M, Baggish AL, Anwaruddin S, Chae CU, Cameron R, Krauser DG, Tung R, Camargo CA Jr, Lloyd-Jones DM (2006) Utility of amino-terminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department. Arch Intern Med 166:315–320CrossRefPubMedGoogle Scholar
  28. 28.
    Bettencourt P, Azevedo A, Pimenta J, Friões F, Ferreira S, Ferreira A (2004) N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients. Circulation 110:2168–2174CrossRefPubMedGoogle Scholar
  29. 29.
    Logeart D, Thabut G, Jourdain P, Chavelas C, Beyne P, Beauvais F, Bouvier E, Solal AC (2004) Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure. J Am Coll Cardiol 43:635–641CrossRefPubMedGoogle Scholar
  30. 30.
    Waldo SW, Beede J, Isakson S, Villard-Saussine S, Fareh J, Clopton P, Fitzgerald RL, Maisel AS (2008) Pro-B-type natriuretic peptide levels in acute decompensated heart failure. Am Coll Cardiol 51:1874–1882CrossRefGoogle Scholar
  31. 31.
    Metra M, Nodari S, Parrinello G, Specchia C, Brentana L, Rocca P, Fracassi F, Bordonali T, Milani P, Danesi R, Verzura G, Chiari E, Dei Cas L (2007) The role of plasma biomarkers in acute heart failure. Serial changes and independent prognostic value of NT-proBNP and cardiac troponin-T. Eur J Heart Fail 9:776–786CrossRefPubMedGoogle Scholar
  32. 32.
    Bayes-Genis A, Pascual-Figal D, Fabregat J, Domingo M, Planas F, Casas T, Ordoñez-Llanos J, Valdes M, Cinca J (2007) Serial NT-proBNP monitoring and outcomes in outpatients with decompensation of heart failure. Int J Cardiol 120:338–343CrossRefPubMedGoogle Scholar
  33. 33.
    Pascual-Figal DA, Domingo M, Casas T, Gich I, Ordoñez-Llanos J, Martínez P, Cinca J, Valdés M, Januzzi JL, Bayes-Genis A (2008) Usefulness of clinical and NT-proBNP monitoring for prognostic guidance in destabilized heart failure outpatients. Eur Heart J 29:1011–1018CrossRefPubMedGoogle Scholar
  34. 34.
    Masson S, Latini R, Anand IS, Barlera S, Angelici L, Vago T, Tognoni G, Cohn JN, Val-HeFT Investigators (2008) Prognostic value of changes in N-terminal pro-brain natriuretic peptide in Val-HeFT (Valsartan Heart Failure Trial). J Am Coll Cardiol 52:997–1003CrossRefPubMedGoogle Scholar
  35. 35.
    Latini R, Masson S, Wong M, Barlera S, Carretta E, Staszewsky L, Vago T, Maggioni AP, Anand IS, Tan LB, Tognoni G, Cohn JN, Val-HeFT Investigators (2006) Incremental prognostic value of changes in B-type natriuretic peptide in heart failure. Am J Med 119:70.e23–70.e30CrossRefGoogle Scholar
  36. 36.
    Hartmann F, Packer M, Coats AJ, Fowler MB, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Trawinski J, Amann-Zalan I, Hoersch S, Katus HA (2004) NT-proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT-proBNP substudy. Eur J Heart Fail 6:343–350CrossRefPubMedGoogle Scholar
  37. 37.
    Olsson LG, Swedberg K, Cleland JG, Spark PA, Komajda M, Metra M, Torp-Pedersen C, Remme WJ, Scherhag A, Poole-Wilson P, COMET Investigators (2007) Prognostic importance of plasma NT-pro BNP in chronic heart failure in patients treated with a beta-blocker: results from the Carvedilol Or Metoprolol European Trial (COMET) trial. Eur J Heart Fail 9:795–801CrossRefPubMedGoogle Scholar
  38. 38.
    Miller WL, Hartman KA, Grill DE, Burnett JC Jr, Jaffe AS (2009) Only large reductions in concentrations of natriuretic peptides (BNP and NT-proBNP) are associated with improved outcome in ambulatory patients with chronic heart failure. Clin Chem 55:78–84CrossRefPubMedGoogle Scholar
  39. 39.
    Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM (2000) Treatment of heart failure guided by plasma aminoter-minal brain natriuretic peptide (N-BNP) concentrations. Lancet 355:1126–1130CrossRefPubMedGoogle Scholar
  40. 40.
    Jourdain P, Jondeau G, Funck F, Gueffet P, Le Helloco A, Donal E, Aupetit JF, Aumont MC, Galinier M, Eicher JC, Cohen-Solal A, Juilliere Y (2007) Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP Multicenter Study. J Am Coll Cardiol 49:1733–1739CrossRefPubMedGoogle Scholar
  41. 41.
    Brunner-La Rocca HP, Buser PT, Schindler R, Bernheim A, Rickenbacher P, Pfisterer M (2006) Management of elderly patients with congestive heart failure—design of the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF). Am Heart J 151:949–955CrossRefPubMedGoogle Scholar
  42. 42.
    Pfisterer M, Buser P, Rickli H, Gutmann M, Erne P, Rickenbacher P, Vuillomenet A, Jeker U, Dubach P, Beer H, Yoon SI, Suter T, Osterhues HH, Schieber MM, Hilti P, Schindler R, Brunner-La Rocca HP, TIME-CHF Investigators (2009) BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial. JAMA 301:383–392CrossRefPubMedGoogle Scholar
  43. 43.
    Piña IL, O’Connor C (2009) BNP-guided therapy for heart failure. JAMA 301:432–434CrossRefPubMedGoogle Scholar
  44. 44.
    Shah MR, Claise KA, Bowers MT, Bhapkar M, Little J, Nohria A, Gaulden LH, McKee VK, Cozart KL, Mancinelli KL, Daniels H, Kinard T, Stevenson LW, Mancini DM, O’Connor CM, Califf RM (2005) Testing new targets of therapy in advanced heart failure: the design and rationale of the Strategies for Tailoring Advanced Heart Failure Regimens in the Outpatient Setting. BRain NatrIuretic Peptide Versus the Clinical CongesTion ScorE (STARBRITE) trial. Am Heart J 150:893–898CrossRefPubMedGoogle Scholar
  45. 45.
    Shah MR for the STARBRITE Investigators (2006) STARBRITE: a randomized pilot trial of BNP-guided therapy in patients with advanced heart failure. Circulation 114(abst II):528Google Scholar
  46. 46.
    Lainchbury JG, Troughton RW, Frampton CM, Yandle TG, Hamid A, Nicholls MG, Richards AM (2006) NTproBNP-guided drug treatment for chronic heart failure: design and methods in the “BATTLESCARRED” trial. Eur J Heart Fail 8:532–538CrossRefPubMedGoogle Scholar
  47. 47.
    Schou M, Gustafsson F, Videbaek L, Markenvard J, Ulriksen H, Ryde H, Jensen JC, Nielsen T, Knudsen AS, Tuxen CD, Handberg J, Sørensen PJ, Espersen G, Lind-Rasmussen S, Keller N, Egstrup K, Nielsen OW, Abdulla J, Nyvad O, Toft J, Hildebrandt PR (2008) Design and methodology of the NorthStar Study: NT-proBNP stratified follow-up in outpatient heart failure clinics—a randomized Danish multicenter study. Am Heart J 156:649–655CrossRefPubMedGoogle Scholar
  48. 48.
    Schou M, Gustafsson F, Nielsen PH, Madsen LH, Kjaer A, Hildebrandt PR (2007) Unexplained week-to-week variation in BNP and NT-proBNP is low in chronic heart failure patients during steady state. Eur J Heart Fail 9:68–74CrossRefPubMedGoogle Scholar
  49. 49.
    Takeda Y, Takeda Y, Suzuki S, Kimura G (2009) Within-person variation of the plasma concentration of B-type natriuretic peptide: safety range in stable patients with heart failure. Am Heart J 157:97–101CrossRefPubMedGoogle Scholar
  50. 50.
    Araújo JP, Azevedo A, Lourenço P, Rocha-Gonçalves F, Ferreira A, Bettencourt P (2006) Intraindividual variation of amino-terminal pro-B-type natriuretic peptide levels in patients with stable heart failure. Am J Cardiol 98:1248–1250CrossRefPubMedGoogle Scholar
  51. 51.
    O’Hanlon R, O’Shea P, Ledwidge M, O’Loughlin C, Lange S, Conlon C, Phelan D, Cunningham S, McDonald KJ (2007) The biologic variability of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide in stable heart failure patients. Card Fail 13:50–55CrossRefGoogle Scholar
  52. 52.
    Wu AH (2006) Serial testing of B-type natriuretic peptide and NTpro-BNP for monitoring therapy of heart failure: the role of biologic variation in the interpretation of results. Am Heart J 152:828–834CrossRefPubMedGoogle Scholar
  53. 53.
    Adams KF Jr (2001) Which beta-blocker for heart failure? Am Heart J 141:884–888CrossRefPubMedGoogle Scholar
  54. 54.
    Rosenberg J, Gustafsson F, Remme WJ, Riegger GA, Hildebrandt PR (2008) Effect of beta-blockade and ACE inhibition on B-type natriuretic peptides in stable patients with systolic heart failure. Cardiovasc Drugs Ther 22:305–311CrossRefPubMedGoogle Scholar
  55. 55.
    Fung JW, Yu CM, Yip G, Chan S, Yandle TG, Richards AM, Nicholls MG, Sanderson JE (2003) Effect of beta blockade (carvedilol or metoprolol) on activation of the renin-angiotensin-aldosterone system and natriuretic peptides in chronic heart failure. Am J Cardiol 92:406–410CrossRefPubMedGoogle Scholar
  56. 56.
    Davis ME, Richards AM, Nicholls MG, Yandle TG, Frampton CM, Troughton RW (2006) Introduction of metoprolol increases plasma B-type cardiac natriuretic peptides in mild, stable heart failure. Circulation 113:977–985CrossRefPubMedGoogle Scholar
  57. 57.
    Yoshizawa A, Yoshikawa T, Nakamura I, Satoh T, Moritani K, Suzuki M, Baba A, Iwanaga S, Mitamura H, Ogawa S (2004) Brain natriuretic peptide response is heterogeneous during beta-blocker therapy for congestive heart failure. J Card Fail 10:310–315CrossRefPubMedGoogle Scholar
  58. 58.
    Hara Y, Hamada M, Shigematsu Y, Suzuki M, Kodama K, Kuwahara T, Hashida H, Ikeda S, Ohtsuka T, Hiasa G, Hiwada K (2000) Effect of beta-blocker on left ventricular function and natriuretic peptides in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitor. Jpn Circ J 64:365–369CrossRefPubMedGoogle Scholar
  59. 59.
    Lee DS, Austin PC, Rouleau JL, Liu PP, Naimark D, Tu JV (2003) Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA 290:2581–2587CrossRefPubMedGoogle Scholar
  60. 60.
    Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C, Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators (2007) Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA 297:1319–1331CrossRefPubMedGoogle Scholar
  61. 61.
    Gheorghiade M, Pang PS (2009) Acute heart failure syndromes. J Am Coll Cardiol 53:557–573CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Kirkwood F. AdamsJr.
    • 1
  • G. Michael Felker
    • 4
  • Ghassan Fraij
    • 2
  • J. Herbert Patterson
    • 3
  • Christopher M. O’Connor
    • 4
  1. 1.Departments of Medicine and Radiology, School of Medicine, UNC Heart Failure ProgramUniversity of North Carolina at Chapel Hill730 Martin Luther King Jr. Blvd., Suite 207Chapel HillUSA
  2. 2.Department of MedicineUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.School of PharmacyUniversity of North Carolina at Chapel HillChapel HillUSA
  4. 4.Department of Medicine, Duke Clinical Research InstituteDuke University School of MedicineDurhamUSA

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