Use of levosimendan in a department of internal medicine: our clinical experience in chronic heart failure. A case series

Background: Levosimendan is a pyridazone-dinitrile derivative. Its primary action is to increase cardiac contractility: binding to troponin C in a calcium-dependent manner and stabilizing it, levodimendan induces actomyosin cross-bridging without increasing myocardial consumption of adenosine triphosphate (ATP) or intracellular calcium concentration. Thus, cardiac performance and contractility are improved with no increase in the total myocardial energy demand and oxygen consumption. Exerting its effects mainly during systole, regular ventricular filling and coronaric flow are preserved in dyastole. Moreover, arrhytmogenesis is not increased as total intracellular calcium levels are not raised. Levosimendan’s peripheral actions are mainly related do vasodilatation, with reduction of cardiac afterload. Independent to the beta-adrenergic pathway, levosimendan increases cardiac inotropism, reduces peripheral vasoconstriction even in presence of the beneficial effects of beta-blockade. Clinical trials have already evaluated the potential clinical application of this drug in acute decompensated heart failure (AHF), without being conclusive for a definite beneficial effect of levosimendan on major outcomes over classic inotropic drugs, such as beta-agonists [1, 2], actually representing an expensive, secondline option in this setting. On the other hand, only small, nonrandomized studies have evaluated the role of the pulsed i.v. administration of this drug in patients affected by chronic heart failure (CHF) with low ejection fraction [3, 4]. To our knowledge, one RCT has been performed on a the oral formulation of levosimendan in this setting [5], and a larger trial on the i.v. pulsed administration is still ongoing [6]. Aims of the study: To describe how pulsed, chronic i.v. administration of levosimendan affected survival, funtional class, number of admissions due to AHF and ejection fraction in ten patients with chronic, compensated heart failure followed by our Internal Medicine department. Materials and methods: Ten consecutive male patients, homogeneous for pathology (postischemic hypertrophic-dilated cardiopathy) and functional class (NYHA class IIIB-IV) were selected for pulsed administration of levosimendan, 0.15 lg/kg/min every 3 weeks starting from 01/01/2007. History and physical examination were performed every admission. Echocardiography and BNP were performed at the time of the first infusion and every 3 months. Statistical analysis was performed with SPSS 13.0 for Windows. Results: Mean age of the group was 76 ± 12 years. All the patients were under therapy with beta-blocker, an ACE-I or an ARB, loop diuretics, spironolactone or similar anti-aldosteronic drugs and statins. Two patients died for acutely decompensated heart failure (32 and 14 months, respectively, after the first infusion). 40% of the group needed further admissions for acutely decompensated heart failure. Mean survival of the group was 25.6 ± 16.5 months. Ejection fraction was 30.8 ± 6.2% at baseline and increased to 40 ± 5.9% at 3 months (p\0.05, using Wilcoxon Signed rank test and t test for repeated measures). BNP mean level was 718. ± 227.2 ng/ml at baseline and decreased to 503 ± 159.3 ng/ml at 3 months (p\0.05, using Wilcoxon Signed rank test and t test for repeated measures). NYHA class remained constant within the controls (p[0.05 using Chi-squared test). Discussion: In this small case series, survival and rehospitalization rates were lower than the ones described in literature [7]. We also observed an overall improvement of echocardiographic and laboratoristic parameters in patients undergoing to levosimendan therapy. Since large, randomized, studies of the use of this drug in chronic, compensated heart failure are still ongoing [6], our data are only suggestive fore possible a role of i.v. administration of levosimendan in manteinance therapy in CHF. These data are consistent with those already described in other studies [3, 4]. References 1. Follath F, Cleland JG et al (2002) Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised doubleblind trial. Lancet 360(9328):196–202 2. Mebazaa A, Nieminen MS et al (2007) Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE randomized trial. JAMA 297(17):1883–1891 3. Nanas JN, Papazoglou P et al (2005) Efficacy and safety of intermittent, long-term, concomitant dobutamine and levosimendan infusions in severe heart failure refractory to dobutamine alone. Am J Cardiol 95(6):768–771 4. Drakos SG, Kanakakis JV et al (2009) Intermittent inotropic infusions combined with prophylactic oral amiodarone for patients with decompensated end-stage heart failure. J Cardiovasc Pharmacol 53(2):157–161 (PubMed PMID: 19188832) 5. Nieminen MS, Cleland JG et al (2008) Oral levosimendan in patients with severe chronic heart failure—the PERSIST study. Eur J Heart Fail 10(12):1246–1254 (Epub 2008 Oct 21) S92 Intern Emerg Med (2010) 5 (Suppl 2):S91–S128 123 6. Altenberger J, Parissis JT, Ulmer H, Poelzl G, LevoRep Investigators (2010) Rationale and design of the multicentre randomized trial investigating the efficacy and safety of pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep study). Eur J Heart Fail 12(2):186–192 7. Fauci AS, Braunwald E et al (1998) Harrison’s Principles of Internal Medicine, 17th edn. McGraw-Hill, New York This contribution has been awarded as Best Communication.