The Role of B-Type Natriuretic Peptide Testing in Guiding Outpatient Heart Failure Treatment

Heart Failure (J Fang, Section Editor)

Opinion statement

While heart failure (HF) treatment guidelines exist, there are significant gaps in their implementation owing in part to the lack of objective data to help guide clinicians in their medical decision-making. B-type natriuretic peptide (BNP) and its amino-terminal equivalent (NT-proBNP) are objective markers of HF prognosis, are useful to monitor response to treatment in outpatients with HF, and may have a role in “guiding” HF care as well. Successful BNP or NT-proBNP guided HF treatment requires regular attempts to reach and maintain target values (BNP ≤ 125 pg/mL or NT-proBNP ≤ 1000 pg/mL). This may be achieved through lifestyle modifications, exercise programs, medication adjustments, and therapeutic interventions shown to reduce morbidity and mortality in HF patients. Failure to achieve biomarker targets portends a worse prognosis, proportional to the lowest achieved natriuretic peptide concentration; in those with significant biomarker “nonresponse,” prognosis is poor, and alternative therapeutic strategies should be considered.

Keywords

Biomarkers Natriuretic peptide Heart failure Management Prognosis Outpatient Pharmacotherapy Cardiac resynchronization Therapy Exercise 

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–e220.PubMedCrossRefGoogle Scholar
  2. 2.
    Kochanek KD, Xu JQ, Murphy SL, Miniño AM, Kung HC. National Vital Statistics Rep. 2011;60(3).Google Scholar
  3. 3.
    Fonarow GC, Yancy CW, Albert NM, et al. Heart failure care in the outpatient cardiology practice setting: findings from IMPROVE HF. Circ Heart Fail. 2008;1(2):98–106.PubMedCrossRefGoogle Scholar
  4. 4.
    Scott PA, Townsend PA, Ng LL, et al. Defining potential to benefit from implantable cardioverter defibrillator therapy: the role of biomarkers. Europace. 2011;13(10):1419–27.PubMedCrossRefGoogle Scholar
  5. 5.
    Kubanek M, Goode KM, Lanska V, Clark AL, Cleland JG. The prognostic value of repeated measurement of N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure due to left ventricular systolic dysfunction. Eur J Heart Fail. 2009;11(4):367–77.PubMedCrossRefGoogle Scholar
  6. 6.
    Masson S, Latini R, Anand IS, et al. Prognostic value of changes in N-terminal pro-brain natriuretic peptide in val-HeFT (valsartan heart failure trial). J Am Coll Cardiol. 2008;52(12):997–1003.PubMedCrossRefGoogle Scholar
  7. 7.
    Latini R, Masson S, Wong M, et al. Incremental prognostic value of changes in B-type natriuretic peptide in heart failure. Am J Med. 2006;119(1):70.e23–30.CrossRefGoogle Scholar
  8. 8.
    Masson S, Latini R, Anand IS, et al. Direct comparison of B-type natriuretic peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the valsartan heart failure (val-HeFT) data. Clin Chem. 2006;52(8):1528–38.PubMedCrossRefGoogle Scholar
  9. 9.
    Pascual-Figal DA, Domingo M, Casas T, et al. Usefulness of clinical and NT-proBNP monitoring for prognostic guidance in destabilized heart failure outpatients. Eur Heart J. 2008;29(8):1011–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Schou M, Gustafsson F, Nielsen PH, et al. Unexplained week-to-week variation in BNP and NT-proBNP is low in chronic heart failure patients during steady state. Eur J Heart Fail. 2007;9(1):68–74.PubMedCrossRefGoogle Scholar
  11. 11.
    Araujo JP, Azevedo A, Lourenco P, et al. Intraindividual variation of amino-terminal pro-B-type natriuretic peptide levels in patients with stable heart failure. Am J Cardiol. 2006;98(9):1248–50.PubMedCrossRefGoogle Scholar
  12. 12.
    Troughton RW, Frampton CM, Yandle TG, et al. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet. 2000;355(9210):1126–30.PubMedCrossRefGoogle Scholar
  13. 13.
    Felker GM, Hasselblad V, Hernandez AF, O'Connor CM. Biomarker-guided therapy in chronic heart failure: a meta-analysis of randomized controlled trials. Am Heart J. 2009;158(3):422–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H. B-type natriuretic peptide-guided heart failure therapy: a meta-analysis. Arch Intern Med. 2010;170(6):507–14.PubMedCrossRefGoogle Scholar
  15. 15.•
    Shah MR, Califf RM, Nohria A, et al. The STARBRITE trial: a randomized, pilot study of B-type natriuretic peptide-guided therapy in patients with advanced heart failure. J Card Fail. 2011;17(8):613–21. A neutral biomarker guided HF therapy study due to an inappropriately high target BNP concentration and inadequate natriuretic peptide lowering.PubMedCrossRefGoogle Scholar
  16. 16.•
    Eurlings LW, van Pol PE, Kok WE, et al. Management of chronic heart failure guided by individual N-terminal pro-B-type natriuretic peptide targets: results of the PRIMA (can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study. J Am Coll Cardiol. 2010;56(25):2090–100. A neutral biomarker guided HF therapy study, which showed that therapy based on individualized target concentrations of NT-proBNP, set at hospital discharge or 2 weeks post-hospital discharge, did not significantly improve mortality, likely because the target concentrations of NT-proBNP were too high to be clinically beneficial.PubMedCrossRefGoogle Scholar
  17. 17.
    Jourdain P, Jondeau G, Funck F, et al. Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP multicenter study. J Am Coll Cardiol. 2007;49(16):1733–9.PubMedCrossRefGoogle Scholar
  18. 18.••
    Berger R, Moertl D, Peter S, et al. N-terminal pro-B-type natriuretic peptide-guided, intensive patient management in addition to multidisciplinary care in chronic heart failure: a 3-arm, prospective, randomized pilot study. J Am Coll Cardiol. 2010;55(7):645–53. Three-Arm prospective study comparing usual care, multidisciplinary care, and NT-proBNP guided HF care. This study showed that when compared with multidisciplinary care, NT-proBNP guided care significantly reduced days of HF hospitalization.PubMedCrossRefGoogle Scholar
  19. 19.••
    Januzzi Jr JL, Rehman SU, Mohammed AA, et al. Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction. J Am Coll Cardiol. 2011;58(18):1881–9. Randomized controlled trial of biomarker guided HF therapy, which showed that when compared to standard of care management, NT-proBNP guided care led to significantly fewer cardiovascular events and improved quality of life and LV function. This study also suggested that close clinical follow-up, especially in elderly patients, may be an essential component of successful biomarker guided HF therapy.PubMedCrossRefGoogle Scholar
  20. 20.
    Januzzi Jr JL. The role of natriuretic peptide testing in guiding chronic heart failure management: review of available data and recommendations for use. Arch Cardiovasc Dis. 2012;105(1):40–50.PubMedCrossRefGoogle Scholar
  21. 21.•
    Weiner RB, Baggish AL, Chen-Tournoux A, et al. Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP outpatient tailored chronic heart failure (PROTECT) study. Eur J Heart Fail. 2013;15(3):342–51 Analysis of data from the PROTECT study showing that NT-proBNP guided care was associated with greater reverse ventricular remodeling and improved cardiovascular structure and function.Google Scholar
  22. 22.
    Lainchbury JG, Troughton RW, Strangman KM, et al. N-terminal pro-B-type natriuretic peptide-guided treatment for chronic heart failure: results from the BATTLESCARRED (NT-proBNP-assisted treatment to lessen serial cardiac readmissions and death) trial. J Am Coll Cardiol. 2009;55(1):53–60.PubMedCrossRefGoogle Scholar
  23. 23.
    Pfisterer M, Buser P, Rickli H, et al. 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. 2009;301(4):383–92.PubMedCrossRefGoogle Scholar
  24. 24.
    Davis ME, Richards AM, Nicholls MG, et al. Introduction of metoprolol increases plasma B-type cardiac natriuretic peptides in mild, stable heart failure. Circulation. 2006;113(7):977–85.PubMedCrossRefGoogle Scholar
  25. 25.
    Richards AM, Doughty R, Nicholls MG, et al. Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand heart failure group. J Am Coll Cardiol. 2001;37(7):1781–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Hartmann F, Packer M, Coats AJ, et al. NT-proBNP in severe chronic heart failure: rationale, design, and preliminary results of the COPERNICUS NT-proBNP substudy. Eur J Heart Fail. 2004;6(3):343–50.PubMedCrossRefGoogle Scholar
  27. 27.
    Hartmann F, Packer M, Coats AJ, et al. Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the carvedilol prospective randomized cumulative survival (COPERNICUS) trial. Circulation. 2004;110(13):1780–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Cohn JN, Tam SW, Anand IS, et al. Isosorbide dinitrate and hydralazine in a fixed-dose combination produces further regression of left ventricular remodeling in a well-treated black population with heart failure: results from A-HeFT. J Card Fail. 2007;13(5):331–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Cole RT, Kalogeropoulos AP, Georgiopoulou VV, et al. Hydralazine and isosorbide dinitrate in heart failure: historical perspective, mechanisms, and future directions. Circulation. 2011;123(21):2414–22.PubMedCrossRefGoogle Scholar
  30. 30.•
    Sanders-van Wijk S, van Asselt AI, Rickli H, et al. Cost-effectiveness of N-terminal Pro-B-type natriuretic-guided therapy in elderly heart failure patients: results from TIME-CHF (Trial of Intensified vs Standard Medical Therapy in Elderly Patients with Congestive Heart Failure). JCHF. 2013;1(1):64–71. Cost-effectiveness analysis of TIME-CHF, one of the largest randomized trials of biomarker guided therapy, which showed that when compared with symptom-guided therapy, NT-proBNP guided therapy was less costly and more effective with more life-years and quality-adjusted life years gained.Google Scholar
  31. 31.
    Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):e391–479.PubMedCrossRefGoogle Scholar
  32. 32.
    RED BOOK® [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.Google Scholar
  33. 33.
    Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351(20):2049–57.PubMedCrossRefGoogle Scholar
  34. 34.
    Berger R, Shankar A, Fruhwald F, et al. Relationships between cardiac resynchronization therapy and N-terminal pro-brain natriuretic peptide in patients with heart failure and markers of cardiac dyssynchrony: an analysis from the cardiac resynchronization in heart failure (CARE-HF) study. Eur Heart J. 2009;30(17):2109–16.PubMedCrossRefGoogle Scholar
  35. 35.
    El-Saed A, Voigt A, Shalaby A. Usefulness of brain natriuretic peptide level at implant in predicting mortality in patients with advanced but stable heart failure receiving cardiac resynchronization therapy. Clin Cardiol. 2009;32(11):E33–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Fruhwald FM, Fahrleitner-Pammer A, Berger R, et al. Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony. Eur Heart J. 2007;28(13):1592–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Magne J, Dubois M, Champagne J, et al. Usefulness of NT-pro BNP monitoring to identify echocardiographic responders following cardiac resynchronization therapy. Cardiovasc Ultrasound. 2009;7:39.PubMedCrossRefGoogle Scholar
  38. 38.
    Chen YM, Li ZB, Zhu M, Cao YM. Effects of exercise training on left ventricular remodeling in heart failure patients: an updated meta-analysis of randomized controlled trials. Int J Clin Pract. 2012;66(8):782–91.PubMedCrossRefGoogle Scholar
  39. 39.
    Davies EJ, Moxham T, Rees K, et al. Exercise training for systolic heart failure: cochrane systematic review and meta-analysis. Eur J Heart Fail. 2010;12(7):706–15.PubMedCrossRefGoogle Scholar
  40. 40.
    Wisloff U, Stoylen A, Loennechen JP, et al. Superior cardiovascular effect of aerobic interval training vs moderate continuous training in heart failure patients: a randomized study. Circulation. 2007;115(24):3086–94.PubMedCrossRefGoogle Scholar
  41. 41.
    Braith RW, Welsch MA, Feigenbaum MS, Kluess HA, Pepine CJ. Neuroendocrine activation in heart failure is modified by endurance exercise training. J Am Coll Cardiol. 1999;34(4):1170–5.PubMedCrossRefGoogle Scholar
  42. 42.
    Smart NA, Steele M. Systematic review of the effect of aerobic and resistance exercise training on systemic brain natriuretic peptide (BNP) and N-terminal BNP expression in heart failure patients. Int J Cardiol. 2010;140(3):260–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Passino C, Severino S, Poletti R, et al. Aerobic training decreases B-type natriuretic peptide expression and adrenergic activation in patients with heart failure. J Am Coll Cardiol. 2006;47(9):1835–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Guazzi M, Vitelli A, Arena R. The effect of exercise training on plasma NT-pro-BNP levels and its correlation with improved exercise ventilatory efficiency in patients with heart failure. Int J Cardiol. 2012;158(2):290–1.PubMedCrossRefGoogle Scholar
  45. 45.
    Schwartz BG, Levine LA, Comstock G, Stecher VJ, Kloner RA. Cardiac uses of phosphodiesterase-5 inhibitors. J Am Coll Cardiol. 2012;59(1):9–15.PubMedCrossRefGoogle Scholar
  46. 46.
    Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail. 2011;4(1):8–17.PubMedCrossRefGoogle Scholar
  47. 47.
    Zhang M, Takimoto E, Lee DI, et al. Pathological cardiac hypertrophy alters intracellular targeting of phosphodiesterase type 5 from nitric oxide synthase-3 to natriuretic peptide signaling. Circulation. 2012;126(8):942–51.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of CardiologyMassachusetts General HospitalBostonUSA

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