Skip to main content

Advertisement

SpringerLink
Log in

Biomarker guided therapy for heart failure: focus on natriuretic peptides

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  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 12:10–38

    Article  Google Scholar 

  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 168:2481–2488

    Article  PubMed  Google Scholar 

  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 26:2706–2713

    Article  PubMed  CAS  Google Scholar 

  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 9:292–299

    Article  PubMed  Google Scholar 

  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):1205–1211

    Article  PubMed  Google Scholar 

  6. Kass DA (2009) Rescuing a failing heart: putting on the squeeze. Nat Med 15:24–25

    Article  PubMed  CAS  Google Scholar 

  7. Anderson ME, Mohler PJ (2009) Rescuing a failing heart: think globally, treat locally. Nat Med 15:25–26

    Article  PubMed  CAS  Google Scholar 

  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 14:823–829

    PubMed  Google Scholar 

  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 45:1654–1664

    Article  PubMed  Google Scholar 

  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 334:942

    Article  PubMed  Google Scholar 

  11. Vasan RS (2006) Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation 113:2335–2362

    Article  PubMed  Google Scholar 

  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–e109

    Article  PubMed  CAS  Google Scholar 

  13. Braunwald E (2008) Biomarkers in heart failure. N Engl J Med 358:2148–2159

    Article  PubMed  CAS  Google Scholar 

  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 10:824–839

    Article  PubMed  CAS  Google Scholar 

  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 137:4–12

    PubMed  CAS  Google Scholar 

  16. Daniels LB, Maisel AS (2007) Natriuretic peptides. J Am Coll Cardiol 50:2357–2368

    Article  PubMed  CAS  Google Scholar 

  17. Rehman SU, Januzzi JL (2008) Natriuretic peptide testing in clinical medicine. Cardiol Rev 16:240–249

    Article  PubMed  Google Scholar 

  18. Martinez-Rumayor A, Richards AM, Burnett JC, Januzzi JL Jr (2008) Biology of the natriuretic peptides. Am J Cardiol 101(3A):3–8

    Article  PubMed  CAS  Google Scholar 

  19. Lee CY, Burnett JC Jr (2007) Natriuretic peptides and therapeutic applications. Heart Fail Rev 12:131–142

    Article  PubMed  CAS  Google Scholar 

  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 41:2280–2287

    Article  PubMed  CAS  Google Scholar 

  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 14:687–694

    Article  PubMed  CAS  Google Scholar 

  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 39:202–209

    Article  PubMed  CAS  Google Scholar 

  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 95:948–954

    Article  PubMed  CAS  Google Scholar 

  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 347:161–167

    Article  PubMed  CAS  Google Scholar 

  25. Jaffe AS, Babuin L (2005) Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ 173:1191–1202

    PubMed  Google Scholar 

  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 358:2117–2126

    Article  PubMed  CAS  Google Scholar 

  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 166:315–320

    Article  PubMed  CAS  Google Scholar 

  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 110:2168–2174

    Article  PubMed  CAS  Google Scholar 

  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 43:635–641

    Article  PubMed  CAS  Google Scholar 

  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 51:1874–1882

    Article  CAS  Google Scholar 

  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 9:776–786

    Article  PubMed  CAS  Google Scholar 

  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 120:338–343

    Article  PubMed  Google Scholar 

  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 29:1011–1018

    Article  PubMed  CAS  Google Scholar 

  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 52:997–1003

    Article  PubMed  CAS  Google Scholar 

  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.e30

    Article  CAS  Google Scholar 

  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 6:343–350

    Article  PubMed  CAS  Google Scholar 

  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 9:795–801

    Article  PubMed  CAS  Google Scholar 

  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 55:78–84

    Article  PubMed  CAS  Google Scholar 

  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 355:1126–1130

    Article  PubMed  CAS  Google Scholar 

  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 49:1733–1739

    Article  PubMed  CAS  Google Scholar 

  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 151:949–955

    Article  PubMed  Google Scholar 

  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 301:383–392

    Article  PubMed  CAS  Google Scholar 

  43. Piña IL, O’Connor C (2009) BNP-guided therapy for heart failure. JAMA 301:432–434

    Article  PubMed  Google Scholar 

  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 150:893–898

    Article  PubMed  Google Scholar 

  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):528

    Google Scholar 

  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 8:532–538

    Article  PubMed  CAS  Google Scholar 

  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 156:649–655

    Article  PubMed  CAS  Google Scholar 

  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 9:68–74

    Article  PubMed  CAS  Google Scholar 

  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 157:97–101

    Article  PubMed  CAS  Google Scholar 

  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 98:1248–1250

    Article  PubMed  CAS  Google Scholar 

  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 13:50–55

    Article  CAS  Google Scholar 

  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 152:828–834

    Article  PubMed  CAS  Google Scholar 

  53. Adams KF Jr (2001) Which beta-blocker for heart failure? Am Heart J 141:884–888

    Article  PubMed  Google Scholar 

  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 22:305–311

    Article  PubMed  CAS  Google Scholar 

  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 92:406–410

    Article  PubMed  CAS  Google Scholar 

  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 113:977–985

    Article  PubMed  CAS  Google Scholar 

  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 10:310–315

    Article  PubMed  CAS  Google Scholar 

  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 64:365–369

    Article  PubMed  CAS  Google Scholar 

  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 290:2581–2587

    Article  PubMed  CAS  Google Scholar 

  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 297:1319–1331

    Article  PubMed  CAS  Google Scholar 

  61. Gheorghiade M, Pang PS (2009) Acute heart failure syndromes. J Am Coll Cardiol 53:557–573

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Medicine and Radiology, School of Medicine, UNC Heart Failure Program, University of North Carolina at Chapel Hill, 730 Martin Luther King Jr. Blvd., Suite 207, Chapel Hill, NC, 27514, USA

    Kirkwood F. Adams Jr.

  2. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Ghassan Fraij

  3. School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    J. Herbert Patterson

  4. Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA

    G. Michael Felker & Christopher M. O’Connor

Authors
  1. Kirkwood F. Adams Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Michael Felker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ghassan Fraij
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Herbert Patterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher M. O’Connor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kirkwood F. Adams Jr..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adams, K.F., Felker, G.M., Fraij, G. et al. Biomarker guided therapy for heart failure: focus on natriuretic peptides. Heart Fail Rev 15, 351–370 (2010). https://doi.org/10.1007/s10741-009-9139-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-009-9139-9

Keywords

Search

Navigation