Skip to main content

Advertisement

SpringerLink
Log in

Treatment with B-Type Natriuretic Peptide for Chronic Decompensated Heart Failure: Insights Learned from the Follow-Up Serial Infusion of Nesiritide (FUSION) Trial

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Several evidence-based treatment regimens are modestly effective in patients with moderately severe to severe heart failure, but truly effective therapies that improve symptoms, reduce hospitalizations, and extend meaningful survival do not exist for these patients. Only ventricular replacement therapy, with either heart transplantation or left ventricular assist devices, has been shown to significantly improve outcomes. Nesiritide, a recombinant B-type natriuretic peptide, is associated with significant reductions in filling pressure, with corresponding relief of symptoms, and diminished neurohormonal levels and has no inotropic effects and no evidence of proarrhythmia when given to patients with decompensated acute heart failure. Results of the Follow-Up Serial Infusion of Nesiritide (FUSION) trial suggest that a regimen incorporating nesiritide can be accomplished with a reasonable assurance of safety and tolerability; pre-study concerns regarding hypotension were not realized. A qualified look at outcomes data within FUSION I suggests that further study of this paradigm is reasonable, especially if the studied patient population includes patients with a low left ventricular ejection fraction and New York Heart Association (NYHA) class III disease with renal insufficiency, or patients with low left ventricular ejection fraction and NYHA class IV heart failure. Therefore, FUSION II, a double-blind, placebo-controlled trial, will randomly assign approximately 900 such patients to treatment with usual care plus nesiritide or usual care plus placebo and will use mortality/cardiorenal hospitalization as a composite end point. If positive data emerge from FUSION II that either confirm or strengthen the data in FUSION I, a new therapeutic option may be available for patients with chronic decompensated heart failure.

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

Similar content being viewed by others

References

  1. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2001;38:2101–2113.

    PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  3. Rales Investigators. Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (The Randomized Aldactone Evaluation Study [RALES]). Am J Cardiol 1996;78:902–907.

    Google Scholar 

  4. Packer M, Fowler MB, Roecker EB, et al. for the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study Group. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: Results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation 2002;106:2194–2199.

    PubMed  Google Scholar 

  5. Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468–1475.

    Article  PubMed  CAS  Google Scholar 

  6. Califf RM, Adams KF, McKenna WJ, et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST). Am Heart J 1997;134:44–54.

    PubMed  CAS  Google Scholar 

  7. Rose EA, Moskowitz AJ, Packer M, et al., the REMATCH Investigators. The REMATCH trial: Rationale, design, and end points. Ann Thorac Surg 1999;67:723–730.

    PubMed  CAS  Google Scholar 

  8. Rose EA, Gelijns AC, Moskowitz AJ, et al. for the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) Study Group. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med 2001;345:1435–1443.

    Article  CAS  PubMed  Google Scholar 

  9. Coffin MR. Dobutamine infusion for the treatment of congestive heart failure in the home care setting. J Intraven Nurs 1994;17:145–150.

    PubMed  CAS  Google Scholar 

  10. Harjai KJ, Mehra MR, Ventura HO, et al. Home inotropic therapy in advanced heart failure. Cost analysis and clinical outcomes. Chest 1997;112:1298–1303.

    PubMed  CAS  Google Scholar 

  11. McCloskey WW. Use of intravenous inotropic therapy in the home. American Journal of Health-Systems Pharmacy 1998;55:930–935.

    CAS  Google Scholar 

  12. Krell MJ, Kline EM, Bates ER, et al. Intermittent, ambulatory dobutamine infusions in patients with severe congestive heart failure. Am Heart J 1986;112:787–791.

    PubMed  CAS  Google Scholar 

  13. Marius-Nunez AL, Heaney L, Fernandez RN, et al. Intermittent inotropic therapy in an outpatient setting: A cost-effective therapeutic modality in patients with refractory heart failure. Am Heart J 1996;132:805–808.

    PubMed  CAS  Google Scholar 

  14. Miller LW, Merkle EJ, Herrmann V. Outpatient dobutamine for end-stage congestive heart failure. Crit Care Med 1990;18:S30–S33.

    PubMed  CAS  Google Scholar 

  15. Roffman DS, Applefeld MM, Grove WR, et al. Intermittent dobutamine hydrochloride infusions in outpatients with chronic congestive heart failure. Clin Pharm 1985;4:195–199.

    PubMed  CAS  Google Scholar 

  16. Van den Brande P, Van Mieghem W, Demedts M. Intermittent dobutamine infusion in severe chronic heart failure in elderly patients. Gerontology 1990;36:49–54.

    Article  PubMed  CAS  Google Scholar 

  17. Boerrigter G, Burnett JC, Jr. Recent advances in natriuretic peptides in congestive heart failure. Expert Opin Investig Drugs 2004;13:643–652.

    PubMed  CAS  Google Scholar 

  18. Mills RM, Hobbs RE, Young JB. “BNP” for heart failure: Role of nesiritide in cardiovascular therapeutics. Congest Heart Fail 2002;8:270–273.

    PubMed  CAS  Google Scholar 

  19. Aronson D, Burger AJ. Intravenous nesiritide (human B-type natriuretic peptide) reduces plasma endothelin-1 levels in patients with decompensated congestive heart failure. Am J Cardiol 2002;90:435–438.

    PubMed  CAS  Google Scholar 

  20. Aronson D, Horton DP, Burger AJ. Nesiritide improves heart rate variability in patients with decompensated heart failure [abstract 4551]. J Am Coll Cardiol 2002;39(suppl B):403B.

    Google Scholar 

  21. Brunner-La Rocca HP, Kaye DM, Woods RL, Hastings J, Esler MD. Effects of intravenous brain natriuretic peptide on regional sympathetic activity in patients with chronic heart failure as compared with healthy control subjects. J Am Coll Cardiol 2001;37:1221–1227.

    PubMed  CAS  Google Scholar 

  22. Yoshimura M, Yasue H, Morita E, et al. Hemodynamic, renal, and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure. Circulation 1991;84:1581–1588.

    CAS  PubMed  Google Scholar 

  23. Marcus LS, Hart D, Packer M, et al. Hemodynamic and renal excretory effects of human brain natriuretic peptide infusion in patients with congestive heart failure. A double-blind, placebo-controlled, randomized crossover trial. Circulation 1996;94:3184–3189.

    PubMed  CAS  Google Scholar 

  24. Abraham WT, Lowes BD, Ferguson DA, et al. Systemic hemodynamic, neurohormonal, and renal effects of a steady-state infusion of human brain natriuretic peptide in patients with hemodynamically decompensated heart failure. J Card Fail 1998;4:37–44.

    PubMed  CAS  Google Scholar 

  25. Tsuruda T, Boerrigter G, Huntley BK, et al. Brain natriuretic Peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases. Circ Res 2002;91:1127–1134.

    PubMed  CAS  Google Scholar 

  26. Colucci WS, Elkayam U, Horton DP, et al., for the Nesiritide Study Group. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. N Engl J Med 2000;343:246–253.

    PubMed  CAS  Google Scholar 

  27. Publication Committee for the VMAC Investigators. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: A randomized controlled trial. JAMA 2002;287:1531–1540.

    Google Scholar 

  28. Peacock WF, Emerman CL, on behalf of the PROACTION Study Group. Safety and efficacy of nesiritide in the treatment of decompensated heart failure in observation patients [abstract 1027-89]. J Am Coll Cardiol 2003;41(suppl A):336A.

    Google Scholar 

  29. Butler J, Emerman C, Peacock WF, Mathur VS, Young JB, on behalf of the VMAC Study Investigators. The efficacy and safety of B-type natriuretic peptide (nesiritide) in patients with renal insufficiency and acutely decompensated congestive heart failure. Nephrol Dial Transplant 2004;19:391–399.

    PubMed  CAS  Google Scholar 

  30. Burger AJ, Elkayam U, Neibaur MT, et al. Comparison of the occurrence of ventricular arrhythmias in patients with acutely decompensated congestive heart failure receiving dobutamine versus nesiritide therapy. Am J Cardiol 2001;88:35–39.

    PubMed  CAS  Google Scholar 

  31. Burger AJ, Horton DP, LeJemtel T, et al. Effect of nesiritide (B-type natriuretic peptide) and dobutamine on ventricular arrhythmias in the treatment of patients with acutely decompensated congestive heart failure: The PRECEDENT Study. Am Heart J 2002;144:1102–1108.

    PubMed  CAS  Google Scholar 

  32. Yancy CW, Saltzberg MT, Berkowitz RL, et al. Safety and feasibility of using serial infusions of nesiritide for heart failure in an outpatient setting (from the FUSION I Trial). Am J Cardiol 2004;94:595–601.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Texas Southwestern Medical Center, Dallas, TX, USA

    Clyde W. Yancy MD

  2. 5323 Harry Hines Blvd, Dallas, Texas, 75390-9047

    Clyde W. Yancy MD

Authors
  1. Clyde W. Yancy MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clyde W. Yancy MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yancy, C.W. Treatment with B-Type Natriuretic Peptide for Chronic Decompensated Heart Failure: Insights Learned from the Follow-Up Serial Infusion of Nesiritide (FUSION) Trial. Heart Fail Rev 9, 209–216 (2005). https://doi.org/10.1007/s10741-005-6132-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-005-6132-9

Keywords

Search

Navigation