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Methods of Assessing the Functional Status of Patients with Left Ventricular Systolic Dysfunction in Interventional Studies: Can Brain Natriuretic Peptide Measurement be Used as Surrogate for the Traditional Methods?

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Abstract

Aim: To review whether brain natriuretic peptides (BNP) can be used as a surrogate for the traditional methods of assessing functional status in interventional studies of patients with left ventricular systolic dysfunction (LVSD).

Methods and results: The traditional methods for assessing functional status including New York Heart Association (NYHA) class, exercise intolerance and quality of life were reviewed in relation to BNP measurements in patients with LVSD. A meta-analysis of four studies evaluating BNP levels versus exercise peak oxygen uptake or 6-minute walking distance showed a significant correlation, but a low R-value of −0.59. Studies using BNP levels for optimisation of heart failure therapy showed conflicting results concerning the correlation between the functional improvement and changes in BNP levels. Conflicting results were also found concerning the utility of BNP levels as a surrogate to predict efficacy of the various anti-congestive therapies on heart failure outcome.

Conclusion: The results of the studies examining BNP measurement as a surrogate for functional status and drug efficacy in patients with LVSD are conflicting. Further studies are necessary to settle the place of BNP measurement as surrogate marker for exercise tolerance, NYHA classification and in assessing efficacy of different interventions in the clinical trials.

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References

  1. Kruger S, Graf J, Kunz D, Stickel T, Hanrath P, Janssens U. brain natriuretic peptide levels predict functional capacity in patients with chronic heart failure. J Am Coll Cardiol 2002;40(4):718–722.

    Google Scholar 

  2. Tjeerdsma G, de Boer RA, Boomsma F, van den Berg MP, Pinto YM, van Veldhuisen DJ. Rapid bedside measurement of brain natriuretic peptide in patients with chronic heart failure. Int J Cardiol 2002;86(2/3):143–149; discussion 149–152.

    Google Scholar 

  3. Wieczorek SJ, Hager D, Barry MB, Kearney L, Ferrier A, Wu AH. Correlation of B-type natriuretic peptide level to 6-min walk test performance in patients with left ventricular systolic dysfunction. Clin Chim. Acta 2003;328(1/2):87–90.

    Google Scholar 

  4. Jourdain P, Funck F, Bellorini M, et al. Bedside B-type natriuretic peptide and functional capacity in chronic heart failure. Eur J Heart Fail 2003;5(2):155–160.

    Google Scholar 

  5. Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002;347(3):161–167.

    Google Scholar 

  6. Van Veldhuisen DJ, Genth-Zotz S, Brouwer J, et al. High-versus low-dose ACE inhibition in chronic heart failure: A double-blind, placebo-controlled study of imidapril. J Am Coll Cardiol 1998;32(7):1811–1818.

    Google Scholar 

  7. Brunner-La Rocca HP, Weilenmann D, Kiowski W, Maly FE, Candinas R, Follath F. Within-patient comparison of effects of different dosages of enalapril on functional capacity and neurohormone levels in patients with chronic heart failure. Am Heart J 1999;138(4 Pt 1):654–662.

    Google Scholar 

  8. Missouris CG, Grouzmann E, Buckley MG, Barron J, MacGregor GA, Singer DR. How does treatment influence endocrine mechanisms in acute severe heart failure? Effects on cardiac natriuretic peptides, the renin system, neuropeptide Y and catecholamines. Clin Sci (Lond) 1998;94(6):591–599.

    Google Scholar 

  9. Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 2000;355(9210):1126–1130.

    Google Scholar 

  10. Maeda K, Tsutamoto T, Wada A, et al. High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure. J Am Coll Cardiol 2000;36(5):1587–1593.

    Google Scholar 

  11. Lee SC, Stevens TL, Sandberg SM, et al. The potential of brain natriuretic peptide as a biomarker for New York Heart Association class during the outpatient treatment of heart failure. J Card Fail 2002;8(3):149–154.

    Google Scholar 

  12. Tang WH, Girod JP, Lee MJ, et al. Plasma B-type natriuretic peptide levels in ambulatory patients with established chronic symptomatic systolic heart failure. Circulation 2003;108(24):2964–2966.

    Google Scholar 

  13. Fung JW, Yu CM, Yip G, et al. 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 2003;92(4):406–410.

    Google Scholar 

  14. Narang R, Swedberg K, Cleland JG. What is the ideal study design for evaluation of treatment for heart failure? Insights from trials assessing the effect of ACE inhibitors on exercise capacity. Eur Heart J 1996;17(1):120–134.

    Google Scholar 

  15. The criteria committee of the New York Heart Association: Anonymous Disease of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis, 7th ed. Boston: Little, Brown & Co. 1973.

  16. Harvey RM DE, Ellis K, et al. Major changes made by the Criteria Committe of the New York Heart Association. Circulation 1974;49:390.

    Google Scholar 

  17. Kleber FX, Niemoller L, Doering W. Impact of converting enzyme inhibition on progression of chronic heart failure: Results of the munich mild heart failure trial. Br Heart J 1992;67(4):289–296.

    Google Scholar 

  18. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med 1987;316(23):1429–1435.

    Google Scholar 

  19. Killip T, 3rd, Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol 1967;20(4):457–464.

    Google Scholar 

  20. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new specific activity scale. Circulation 1981;64(6):1227–1234.

    Google Scholar 

  21. Blackwood R, Mayou RA, Garnham JC, Armstrong C, Bryant B. Exercise capacity and quality of life in the treatment of heart failure. Clin Pharmacol Ther 1990;48(3):325–332.

    Google Scholar 

  22. Rogers WJ, Johnstone DE, Yusuf S, et al. Quality of life among 5,025 patients with left ventricular dysfunction randomized between placebo and enalapril: The Studies of Left Ventricular Dysfunction. The SOLVD Investigators. J Am Coll Cardiol 1994;23(2):393–400.

    Google Scholar 

  23. Gorkin L, Norvell NK, Rosen RC, et al. Assessment of quality of life as observed from the baseline data of the Studies of Left Ventricular Dysfunction (SOLVD) trial quality-of-life substudy. Am J Cardiol 1993;71(12):1069–1073.

    Google Scholar 

  24. Gundersen T, Swedberg K, Amtorp O, Remes J, Nilsson B. Absence of effect on exercise capacity of 12-weeks treatment with ramipril in patients with moderate congestive heart failure. Ramipril Study Group. Eur Heart J 1994;15(12):1659–1665.

    Google Scholar 

  25. Comparison of the effects of cilazapril and captopril versus placebo on exercise testing in chronic heart failure patients: A double-blind, randomized, multicenter trial. The Cilazapril-Captopril Multicenter Group. Cardiology 1995;86(Suppl 1):34–40.

    Google Scholar 

  26. Larsen J, Sykulski R, Jensen G, et al. Adaptive changes in the acute haemodynamic effects of cilazapril during chronic treatment. Comparison with long-term clinical effect. Eur J Clin Pharmacol 1996;50(6):433–441.

    Google Scholar 

  27. Rector TS, Johnson G, Dunkman WB, et al. Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life. V-HeFT II. The V-HeFT VA Cooperative Studies Group. Circulation 1993;87(6 Suppl):VI71–VI77.

    Google Scholar 

  28. Recommendations for exercise testing in chronic heart failure patients. Eur Heart J 2001;22(1):37–45.

  29. Chaitman B. Exercise Stress Testing. In: Braunwald E, ed. Heart Disease, 6th ed. Saunders Co. 2001:129–155.

  30. Szabo BM, Van Veldhuisen DJ, de Graeff PA, Lie KI. Alterations in the prognosis of chronic heart failure: An overview of the major mortality trials. Cardiovasc Drugs Ther 1997;11:427–434.

    Google Scholar 

  31. Cohn JN, Johnson GR, Shabetai R, et al. Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. The V-HeFT VA Cooperative Studies Group. Circulation 1993;87(6 Suppl):VI5–V16.

    Google Scholar 

  32. Aaronson KD, Schwartz JS, Chen TM, Wong KL, Goin JE, Mancini DM. Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. Circulation 1997;95(12):2660–2667.

    Google Scholar 

  33. Likoff MJ, Chandler SL, Kay HR. Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy. Am J Cardiol 1987;59(6):634–638.

    Google Scholar 

  34. de Lemos JA, McGuire DK, Drazner MH. B-type natriuretic peptide in cardiovascular disease. Lancet 2003;362(9380):316–322.

    Google Scholar 

  35. Daly C, Fox K, Henein M. Natriuretic peptides in the diagnosis of heart disease-First amongst equals? Int J Cardiol 2002;84(2/3):107–113.

    Google Scholar 

  36. Gardner RS, Ozalp F, Murday AJ, Robb SD, McDonagh TA. N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure. Eur Heart J 2003;24(19):1735–1743.

    Google Scholar 

  37. 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):1781–1787.

    Google Scholar 

  38. Jernberg T, Stridsberg M, Venge P, Lindahl B. N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation. J Am Coll Cardiol 2002;40(3):437–445.

    Google Scholar 

  39. Hunt PJ, Richards AM, Nicholls MG, Yandle TG, Doughty RN, Espiner EA. Immunoreactive amino-terminal probrain natriuretic peptide (NT-PROBNP): A new marker of cardiac impairment. Clin Endocrinol (Oxf) 1997;47(3):287–296.

    Google Scholar 

  40. Mair J, Hammerer-Lercher A, Puschendorf B. The impact of cardiac natriuretic peptide determination on the diagnosis and management of heart failure. Clin Chem Lab Med 2001;39(7):571–588.

    Google Scholar 

  41. Lainchbury JG, Campbell E, Frampton CM, Yandle TG, Nicholls MG, Richards AM. Brain natriuretic peptide and n-terminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath. J Am Coll Cardiol 2003;42(4):728–735.

    Google Scholar 

  42. Cowie MR, Jourdain P, Maisel A, et al. Clinical applications of B-type natriuretic peptide (BNP) testing. Eur Heart J 2003;24(19):1710–1718.

    Google Scholar 

  43. Hampton JR, Cowley AJ, Wnuk-Wojnar AM. Failure of an ACE inhibitor to improve exercise tolerance. A randomized study of trandolapril. Trandolapril study group. Eur Heart J 1998;19(12):1823–1828.

    Google Scholar 

  44. Latini R, Masson S, Anand I, et al. Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure: The Valsartan Heart Failure Trial (Val-HeFT). Circulation 2002;106(19):2454–2458.

    Google Scholar 

  45. Tsutamoto T, Wada A, Maeda K, et al. Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol 2001;37(5):1228–1233.

    Google Scholar 

  46. Tsutamoto T, Wada A, Maeda K, et al. Digitalis increases brain natriuretic peptide in patients with severe congestive heart failure. Am Heart J 1997;134(5 Pt 1):910–916.

    Google Scholar 

  47. Sanderson JE, Chan WW, Hung YT, et al. Effect of low dose beta blockers on atrial and ventricular (B type) natriuretic factor in heart failure: A double blind, randomised comparison of metoprolol and a third generation vasodilating beta blocker. Br Heart J 1995;74(5):502–507.

    Google Scholar 

  48. Sinha AM, Filzmaier K, Breithardt OA, et al. Usefulness of brain natriuretic peptide release as a surrogate marker of the efficacy of long-term cardiac resynchronization therapy in patients with heart failure. Am J Cardiol 2003;91(6):755–758.

    Google Scholar 

  49. Lee CR, Adams KF, Jr, Patterson JH. Surrogate end points in heart failure. Ann Pharmacother 2002;36(3):479–488.

    Google Scholar 

  50. Lainchbury JG, Richards AM. Exercise testing in the assessment of chronic congestive heart failure. Heart 2002;88(5):538–543.

    Google Scholar 

  51. Lainchbury JG SM, Beckert L, et al. Change in plasma brain natriuretic peptide during exercise is an important predictor of survival in systolic heart failure. European Heart Journal 2001;22(Suppl):377.

    Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Gentofte University Hospital, Denmark

    Jawdat Abdulla

  2. Department of Medicine, Division of Cardiology, Rigshospitalet Heart Centre, Denmark

    Lars Køber

  3. Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark

    Christian Torp-Pedersen

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  1. Jawdat Abdulla
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  2. Lars Køber
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Abdulla, J., Køber, L. & Torp-Pedersen, C. Methods of Assessing the Functional Status of Patients with Left Ventricular Systolic Dysfunction in Interventional Studies: Can Brain Natriuretic Peptide Measurement be Used as Surrogate for the Traditional Methods?. Cardiovasc Drugs Ther 18, 219–224 (2004). https://doi.org/10.1023/B:CARD.0000033643.93393.46

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  • DOI: https://doi.org/10.1023/B:CARD.0000033643.93393.46

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