Skip to main content

Advertisement

SpringerLink
Log in

Classical inotropes and new cardiac enhancers

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Acute heat failure syndromes are a heterogenous group of conditions. Chronic heart failure exacerbations represent the vast majority of cases. Pathophysiologic mechanisms, such as hypotension with peripheral tissue hypoperfusion, renal function impairment and myocardial ischemia and injury, adversely affect patients’ clinical outcome. Classical inotropes, such as beta-agonists (dobutamine, dopamine) and phosphodiesterase inhibitors (milrinone), seem to improve clinical symptoms and hemodynamics of acutely decompensated chronic heat failure patients, but they have been associated with increased long-term mortality. Thus, on the basis of the available evidence, these agents can be used only as a temporary treatment of acute heart failure exacerbations with stringent criteria (ESC AHF guidelines), resistant to intravenous vasodilators and/or diuretics when systolic blood pressure (SBP) is >100 mmHg or as a first-line treatment in patients with worsening of chronic cardiac failure and low SBP (<100 mmHg). The calcium sensitizer levosimendan is a new cardiac enhancer that seems to be more effective than classical inotropes in improving cardiac mechanical efficiency and reducing congestion, without causing cardiomyocyte death or increasing myocardial oxygen uptake. Recent randomized trials showed that levosimendan is not superior to placebo or dobutamine in improving 1- and 6-month mortality, although it caused a greater reduction of neurohormonal response. More data are needed regarding patient selection and the optimum regimen and dosing of levosimendan before this treatment modality become the first line therapy of acutely decompensated chronic heart failure patients.

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

Similar content being viewed by others

References

  1. Adams KF Jr, Fonarow GC, Emerman CL et al (2005) Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 149:209–216

    Article  PubMed  Google Scholar 

  2. Fonarow GC, Corday E (2004) ADHERE Scientific Advisory Committee. Overview of acutely decompensated congestive heart failure (ADHF): a report from the ADHERE registry. Heart Fail Rev 9(3):179–185

    Article  PubMed  Google Scholar 

  3. Cotter M-O, Adams KF, O’Connor CM et al (2007) Acute heart failure associated with high admission blood pressure – a distinct vascular disorder? Eur J Heart Fail 9:178–183

    Article  PubMed  Google Scholar 

  4. Thackray S, Easthaugh J, Freemantle N, Cleland JG (2002) The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure – a meta regression analysis. Eur J Heart Fail 4:515–529

    Article  PubMed  CAS  Google Scholar 

  5. Packer M (1993) The search for the ideal positive inotropic agent. N Engl J Med 329:201–202

    Article  PubMed  CAS  Google Scholar 

  6. Papp Z, Csapo K, Pollesselo P et al (2005) Pharmacological mechanisms contributing to the clinical efficacy of levosimendan. Cardiovasc Drug Rev 23(1):7198

    Google Scholar 

  7. Mebazaa A, Barraud D, Welschbillig S (2005) Randomized clinical trials with levosimendan. Am J Cardiol 96(6A):74G–79G

    Article  PubMed  CAS  Google Scholar 

  8. Munger MA (2006) Management of acute decompensated heart failure: treatment, controversy, and future directions. Pharmacotherapy 26:131S–138S

    Article  PubMed  Google Scholar 

  9. Zannad F, Adamopoulos C, Mebazaa A, Gheorghiade M (2006) The challenge of acute decompensated heart failure. Heart Fail Rev 11(2):135–139

    Article  PubMed  Google Scholar 

  10. Felker GM, O’Connor CM (2001) Inotropic therapy for heart failure: an evidence-based approach. Am Heart J 142:393–401

    Article  PubMed  CAS  Google Scholar 

  11. Nieminen MS, Bohm M, Cowie MR et al (2005) ESC committee for practice guideline. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the task force on acute heart failure of the European society of cardiology. Eur Heart J 26:384–416

    Article  PubMed  Google Scholar 

  12. O’Connor CM, Gattis WA, Uretsky BF et al (1999) Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: insights from the Flolan International Randomized Survival Trial (FIRST). Am Heart J 138:78–86

    Article  PubMed  CAS  Google Scholar 

  13. Follath F, Cleland JG, Just H et al (2002) Steering committee and investigators of the Levosimendan Infusion versus Dobutamine (LIDO) study. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 360:196–202

    Article  PubMed  CAS  Google Scholar 

  14. Cuffe MS, Califf RM, Adams KF Jr et al (2002) Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) investigators. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA 287:1541–1547

    Article  PubMed  CAS  Google Scholar 

  15. Elsasser A, Schlepper M, Klovekorn WP et al (1997) Hibernating myocardium: an incomplete adaptation to ischemia. Circulation 96:2920–2931

    PubMed  CAS  Google Scholar 

  16. Burger AJ, Elkayam U, Neibaur MT, Haught H, Ghali J, Horton DP, Aronson D (2001) Comparison of the occurrence of ventricular arrhythmias in patients with acutely decompensated congestive heart failure receiving dobutamine versus nesiritide therapy. Am J Cardiol 88:35–39

    Article  PubMed  CAS  Google Scholar 

  17. Packer M, Carver JR, Rodeheffer RJ et al (1991) Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 325(21):1468–1475

    Article  PubMed  CAS  Google Scholar 

  18. Packer M, Medina N, Yushak M (1984) Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure. Circulation 70(6):1038–1047

    PubMed  CAS  Google Scholar 

  19. Sharma M, Teerlink JR (2004) A rational approach for the treatment of acute heart failure: current strategies and future options. Curr Opin Cardiol 19:254–263

    Article  PubMed  Google Scholar 

  20. Perrone S, Kaplinsky EJ (2005) Calcium sensitizer agents: a new class of inotropic agents in the treatment of decompensated heart failure. Int J Cardiol 103:248–255

    Article  PubMed  Google Scholar 

  21. Figgit DP, Gilles PS, Goa KL (2001) Levosimendan. Drugs 61:613–627

    Article  Google Scholar 

  22. Kivikko M, Lehtonen L (2005) Levosimendan: a new inodilatory drug for the treatment of decompensated heart failure. Curr Pharm Des 11:435–455

    Article  PubMed  CAS  Google Scholar 

  23. Parissis J, Filippatos G, Farmakis D, Adamopoulos S, Paraskevaidis I, Kremastinos D (2005) Levosimendan for the treatment of acute heart failure syndromes. Exp Opin Pharmacother 6(15):2741–2751

    Article  CAS  Google Scholar 

  24. Michaels AD, Mc Keown B, Kostal M et al (2005) Effects of intravenous levosimendan on human coronary vasomotor regulation, left ventricular wall stress, and myocardial oxygen uptake. Circulation 111:1504–1509

    Article  PubMed  CAS  Google Scholar 

  25. Grossini E, Caimmi PP, Molinari C et al (2005) Hemodynamic effect of intracoronary administration of levosimendan in the anesthetized pig. J Cardiovasc Pharmacol 46:333–342

    Article  PubMed  CAS  Google Scholar 

  26. Maytin M, Colucci W (2005) Cardioprotection: a new paradigm in the acute management of acute heat failure syndromes. Am J Cardiol 96(6A):26G–31G

    Article  PubMed  CAS  Google Scholar 

  27. Adamopoulos S, Parissis J, Iliodromitis E et al (2006) Effects of levosimendan versus dobutamine on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure. Am J Cardiol 98:102–106

    Article  PubMed  CAS  Google Scholar 

  28. Nieminen M, Akkila J, Hasenfuss G et al (2000) Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J Am Coll Cardiol 36(6):1903–1912

    Article  PubMed  CAS  Google Scholar 

  29. Slawsky MT, Colucci WS, Gottlieb S et al (2000) Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation 102:2222–2227

    PubMed  CAS  Google Scholar 

  30. Kyrzopoulos S, Adamopoulos S, Parissis J et al (2005) Levosimendan reduces plasma B-type natriuretic peptide and interleukin-6, and improves central hemodynamics in severe heart failure patients. Int J Cardiol 99:409–413

    Article  PubMed  Google Scholar 

  31. Tachinaba H, Cheng HJ, Ukai T et al (2005) Levosimendan improves LV systolic and diastolic performance at rest and during exercise after heart failure. Am J Physiol Heart Circ Physiol 288:H914–H922

    Article  CAS  Google Scholar 

  32. Parissis J, Panou F, Famakis D et al (2005) Effects of levosimendan on markers of left ventricular diastolic function and neurohormonal activation in patients with advanced heart failure. Am J Cardiol 96:423–426

    Article  PubMed  CAS  Google Scholar 

  33. DeLuca L, Colucci W, Nieminen M, Massie B, Georghiade M (2006) Evidence-based use of levosimendan in different clinical settings. Eur Heart J 27:1908–1920

    Article  CAS  Google Scholar 

  34. Moiseyev VS, Poder P, Andrejevs N et al (2002) RUSSLAN study investigators. Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN). Eur Heart J 23:1422–1432

    Article  PubMed  CAS  Google Scholar 

  35. Vilas-Boas F, Follath F (2006) Current insights into the modern treatment of decompensated heart failure. Arq Bras Cardiol 87:329–337

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Heart Failure Unit, Attikon University Hospital, Athens, Greece

    John T. Parissis & Dimitrios Farmakis

  2. Division of Cardiology, University Central Hospital, Helsinki, Finland

    Markku Nieminen

  3. 17 Aftokratoros Irakliou St, Maroussi, Athens, 15122, Greece

    John T. Parissis

Authors
  1. John T. Parissis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dimitrios Farmakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Markku Nieminen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John T. Parissis.

Additional information

Levosimendan is not approved in the USA.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parissis, J.T., Farmakis, D. & Nieminen, M. Classical inotropes and new cardiac enhancers. Heart Fail Rev 12, 149–156 (2007). https://doi.org/10.1007/s10741-007-9014-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-007-9014-5

Keywords

Search

Navigation