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      Use of levosimendan in acute heart failure

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          Abstract

          As a calcium sensitizer and inodilator that augments cardiac contractility without increasing myocardial oxygen demand or exacerbating ischaemia, levosimendan may be well configured to deliver inotropic support in cases of acute heart failure (AHF). Other factors favouring levosimendan in this setting include its extended duration of action due to the formation of an active metabolite and the lack of any attenuation of effect in patients treated with beta-blockers. Effects of levosimendan on systemic haemodynamics include its significant, dose-dependent increases in cardiac output, stroke volume and heart rate, and decreases in right and left ventricular filling and total peripheral resistance. Rapid and sustained reduction in levels of natriuretic peptides is a consistent effect of levosimendan use and potentially favourable effects on other neurohormonal indicators of cardiac distress are also observed. Levosimendan has repeatedly been shown to be effective in relief of symptoms of AHF, notably dyspnoea and fatigue, while mortality data from clinical trials and registries suggest that levosimendan is markedly less likely than catecholaminergic inotropes to worsen prognosis. The vasodilator pharmacology of levosimendan is also pertinent to the drug’s use in AHF, in which setting organ under-perfusion is often a key pathology. These considerations suggest that levosimendan may have a more favourable impact on the circumstances of the majority of AHF patients than adrenergic agents that act only or primarily as cardiac stimulants. They also suggest that levosimendan may advantageously be integrated into a comprehensive strategy of early intervention designed and intended to prevent cardiac destabilization worsening to the point where hospitalization is necessary. Levosimendan should be used with caution and with tightened haemodynamic monitoring in patients who have low baseline blood pressure (systolic blood pressure <100 mmHg; diastolic blood pressure <60 mmHg), or who are at risk of a hypotensive episode.

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          Most cited references41

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          Clinical picture and risk prediction of short-term mortality in cardiogenic shock.

          The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality.
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            Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial.

            Because acute decompensated heart failure causes substantial morbidity and mortality, there is a need for agents that at least improve hemodynamics and relieve symptoms without adversely affecting survival. To assess the effect of a short-term intravenous infusion of levosimendan or dobutamine on long-term survival. The Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study was a randomized, double-blind trial comparing the efficacy and safety of intravenous levosimendan or dobutamine in 1327 patients hospitalized with acute decompensated heart failure who required inotropic support. The trial was conducted at 75 centers in 9 countries and patients were randomized between March 2003 and December 2004. Intravenous levosimendan (n = 664) or intravenous dobutamine (n = 663). All-cause mortality at 180 days. All-cause mortality at 180 days occurred in 173 (26%) patients in the levosimendan group and 185 (28%) patients in the dobutamine group (hazard ratio, 0.91; 95% confidence interval, 0.74-1.13; P = .40). The levosimendan group had greater decreases in B-type natriuretic peptide level at 24 hours that persisted through 5 days compared with the dobutamine group (P<.001 for all time points). There were no statistical differences between treatment groups for the other secondary end points (all-cause mortality at 31 days, number of days alive and out of the hospital, patient global assessment, patient assessment of dyspnea at 24 hours, and cardiovascular mortality at 180 days). There was a higher incidence of cardiac failure in the dobutamine group. There were higher incidences of atrial fibrillation, hypokalemia, and headache in the levosimendan group. Despite an initial reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group compared with patients in the dobutamine group, levosimendan did not significantly reduce all-cause mortality at 180 days or affect any secondary clinical outcomes. clinicaltrials.gov Identifier: NCT00348504.
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              Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure.

              This study evaluated the efficacy and safety of levosimendan, a positive inotropic drug with vasodilator effects, given intravenously to patients with acutely decompensated heart failure (ADHF).
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                Author and article information

                Journal
                Eur Heart J Suppl
                Eur Heart J Suppl
                ehjsupp
                European Heart Journal Supplements : Journal of the European Society of Cardiology
                Oxford University Press
                1520-765X
                1554-2815
                December 2018
                11 December 2018
                11 December 2018
                : 20
                : Suppl I , Levosimendan in Acute and Advanced Heart Failure
                : I2-I10
                Affiliations
                [1 ]Department of Cardiology, Helsinki University Hospital, Helsinki, Finland
                [2 ]Cardiology Department, AHEPA University Hospital, Thessaloniki, Greece
                [3 ]Division of Cardiology, Medical University of Graz, Graz, Austria
                [4 ]Lomonosov Moscow State University Medical Centre, Moscow, Russia
                [5 ]Department of Anaesthesia and Intensive Care, INSERM UMR 942, Lariboisière Hospital, University of Paris, Paris, France
                [6 ]Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
                [7 ]Medizinische Klinik II, Klinikum Weiden, Akademisches Lehrkrankenhaus der Universität Regensburg, Regensburg, Germany
                [8 ]Orion Pharma, Critical Care Proprietary Products, PO Box 65, FIN-02101 Espoo, Finland
                [9 ]Second Cardiology Department and Heart Failure Unit, Attikon Teaching Hospital, Athens, Greece
                Author notes
                Corresponding author. Tel: +358509664191, Fax: +359104263815, Email: piero.pollesello@ 123456orionpharma.com
                Article
                suy039
                10.1093/eurheartj/suy039
                6288642
                30555279
                cdcc9c09-622b-421d-a69f-61db4de53e34
                Published on behalf of the European Society of Cardiology. © The Author(s) 2018.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Page count
                Pages: 9
                Categories
                Articles

                inotrope,inodilator,cardioactive,vasoactive,treatment,efficacy,safety

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