Ularitide in Acute Heart Failure

  • Tina Shah
  • June Kampangkaew
  • Ryle Przybylowicz
  • Anita Deswal
Heart Failure (F Peacock and L Zhang, Section Editors)
Part of the following topical collections:
  1. Heart Failure


Purpose of Review

This review article will summarize the currently available data for ularitide in acute decompensated heart failure (ADHF).

Recent Findings

Hospitalization for ADHF represents a key prognostic event in the time course of many patients with HF. It is associated with a high risk for rehospitalization (~ 50% at 6 months) and 1-year mortality rate (~ 30%).


There is an unmet need for agents that will improve symptoms and outcomes for clinical outcomes in ADHF. Several agents with vasodilating properties have been studied in this population, but there is limited data demonstrating definitive efficacy of currently available therapies. Ularitide is a synthetic form of urodilatin, a natriuretic peptide produced in the distal renal tubule cells.


Acute decompensated HF (ADHF) Heart failure (HF) Ularitide 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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

  1. 1.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147–239. Scholar
  2. 2.
    Allen LA, O’Connor CM. Management of acute decompensated heart failure. CMAJ: Can Med Assoc J. 2007;176(6):797–805.CrossRefGoogle Scholar
  3. 3.
    Ignarro LJ. After 130 years, the molecular mechanism of action of nitroglycerin is revealed. Proc Natl Acad Sci U S A. 2002;99(12):7816–7. Scholar
  4. 4.
    Aziz EF, Kukin M, Javed F, Pratap B, Sabharwal MS, Tormey D, et al. Effect of adding nitroglycerin to early diuretic therapy on the morbidity and mortality of patients with chronic kidney disease presenting with acute decompensated heart failure. Hospital practice (1995). 2011;39(1):126–32. Scholar
  5. 5.
    • Singh A, Laribi S, Teerlink JR, Mebazaa A. Agents with vasodilator properties in acute heart failure. Eur Heart J. 2017;38(5):317–25. Review of the agents with vasodilator properties in the treatment of acute decompensated heart failure. Scholar
  6. 6.
    Schulz-Knappe P, Forssmann K, Herbst F, Hock D, Pipkorn R, Forssmann WG. Isolation and structural analysis of “urodilatin”, a new peptide of the cardiodilatin-(ANP)-family, extracted from human urine. Klin Wochenschr. 1988;66(17):752–9. Scholar
  7. 7.
    Forssmann WG, Richter R, Meyer M. The endocrine heart and natriuretic peptides: histochemistry, cell biology, and functional aspects of the renal urodilatin system. Histochem Cell Biol. 1998;110(4):335–57.CrossRefPubMedGoogle Scholar
  8. 8.
    Goetz K, Drummer C, Zhu JL, Leadley R, Fiedler F, Gerzer R. Evidence that urodilatin, rather than ANP, regulates renal sodium excretion. J Am Soc Nephrol. 1990;1(6):867–74.PubMedGoogle Scholar
  9. 9.
    Mitrovic V, Hernandez AF, Meyer M, Gheorghiade M. Role of guanylate cyclase modulators in decompensated heart failure. Heart Fail Rev. 2009;14(4):309–19. Scholar
  10. 10.
    Gagelmann M, Hock D, Forssmann WG. Urodilatin (CDD/ANP-95-126) is not biologically inactivated by a peptidase from dog kidney cortex membranes in contrast to atrial natriuretic peptide/cardiodilatin (alpha-hANP/CDD-99-126). FEBS Lett. 1988;233(2):249–54. Scholar
  11. 11.
    Anker SD, Ponikowski P, Mitrovic V, Peacock WF, Filippatos G. Ularitide for the treatment of acute decompensated heart failure: from preclinical to clinical studies. Eur Heart J. 2015;36(12):715–23. Scholar
  12. 12.
    Abassi ZA, Powell JR, Golomb E, Keiser HR. Renal and systemic effects of urodilatin in rats with high-output heart failure. Am J Phys. 1992;262(4 Pt 2):F615–21.Google Scholar
  13. 13.
    Villarreal D, Freeman RH, Johnson RA. Renal effects of ANF (95-126), a new atrial peptide analogue, in dogs with experimental heart failure. Am J Hypertens. 1991;4(6):508–15. Scholar
  14. 14.
    Kentsch M, Ludwig D, Drummer C, Gerzer R, Müller-Esch G. Haemodynamic and renal effects of urodilatin in healthy volunteers. Eur J Clin Investig. 1992;22(5):319–25. Scholar
  15. 15.
    Carstens J, Jensen KT, Pedersen EB. Metabolism and action of urodilatin infusion in healthy volunteers. Clin Pharmacol Ther. 1998;64(1):73–86. Scholar
  16. 16.
    Kentsch M, Ludwig D, Drummer C, Gerzer R, Müller-Esch G. Haemodynamic and renal effects of urodilatin bolus injections in patients with congestive heart failure. Eur J Clin Investig. 1992;22(10):662–9. Scholar
  17. 17.
    Elsner D, Muders F, Müntze A, Kromer EP, Forssmann WG, Riegger GA. Efficacy of prolonged infusion of urodilatin [ANP-(95-126)] in patients with congestive heart failure. Am Heart J. 1995;129(4):766–73. Scholar
  18. 18.
    Mitrovic V, Lüss H, Nitsche K, Forssmann K, Maronde E, Fricke K, et al. Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. Am Heart J. 2005;150(6):1239. Scholar
  19. 19.
    Mitrovic V, Seferovic PM, Simeunovic D, Ristic AD, Miric M, Moiseyev VS, et al. Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J. 2006;27(23):2823–32. Scholar
  20. 20.
    Lüss H, Mitrovic V, Seferovic PM, Simeunovic D, Ristić AD, Moiseyev VS, et al. Renal effects of ularitide in patients with decompensated heart failure. Am Heart J. 2008;155(6):1012.e1–8. Scholar
  21. 21.
    •• Packer M, O’Connor C, McMurray JJV, Wittes J, Abraham WT, Anker SD, et al. Effect of ularitide on cardiovascular mortality in acute heart failure. N Engl J Med. 2017;376(20):1956–64. Trial showing effect of ularitide on cardiovascular mortality in patients with acute decompnesated heart failure.CrossRefPubMedGoogle Scholar
  22. 22.
    •• Teerlink JR, Voors AA, Ponikowski P, Pang PS, Greenberg BH, Filippatos G, et al. Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study. Eur J Heart Fail. 2017;19(6):800–9. Describes design of the RELAX-AHF-2 trial.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    O’Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011;365(1):32–43. Scholar
  24. 24.
    •• Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet. 2013;381(9860):29–39. Important trial of outcomes of serelaxin in heart failure patients. Scholar
  25. 25.
    Serelaxin fails to meet primary endpoints in phase 3 RELAX-AHF-2 trial [press release]. 2017.Google Scholar

Copyright information

© This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection 2018

Authors and Affiliations

  • Tina Shah
    • 1
    • 2
  • June Kampangkaew
    • 3
  • Ryle Przybylowicz
    • 3
  • Anita Deswal
    • 1
    • 2
  1. 1.Section of CardiologyMichael E. DeBakey VA Medical CenterHoustonUSA
  2. 2.Section of CardiologyBaylor College of MedicineHoustonUSA
  3. 3.Department of MedicineBaylor College of MedicineHoustonUSA

Personalised recommendations