Browsing by Subject "Levosimendan"

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  • Farmakis, Dimitrios; Agostoni, Piergiuseppe; Baholli, Loant; Bautin, Andrei; Comin-Colet, Josep; Crespo-Leiro, Maria G.; Fedele, Francesco; García-Pinilla, Jose Manuel; Giannakoulas, George; Grigioni, Francesco; Gruchała, Marcin; Gustafsson, Finn; Harjola, Veli-Pekka; Hasin, Tal; Herpain, Antoine; Iliodromitis, Efstathios K.; Karason, Kristjan; Kivikko, Matti; Liaudet, Lucas; Ljubas-Maček, Jana; Marini, Marco; Masip, Josep; Mebazaa, Alexandre; Nikolaou, Maria; Ostadal, Petr; Põder, Pentti; Pollesello, Piero; Polyzogopoulou, Eftihia; Pölzl, Gerhard; Tschope, Carsten; Varpula, Marjut; von Lewinski, Dirk; Vrtovec, Bojan; Yilmaz, Mehmet Birhan; Zima, Endre; Parissis, John (2019)
    Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure. (C) 2019 The Authors. Published by Elsevier B.V.
  • Bouchez, S.; Fedele, F.; Giannakoulas, G.; Gustafsson, F.; Harjola, V. -P.; Karason, K.; Kivikko, M.; von Lewinski, D.; Oliva, F.; Papp, Z.; Parissis, J.; Pollesello, Piero; Pölzl, G.; Tschöpe, C. (2018)
    Levosimendan, a calcium sensitizer and potassium channel-opener, is widely appreciated by many specialist heart failure practitioners for its effects on systemic and pulmonary hemodynamics and for the relief of symptoms of acute heart failure. The drug's impact on mortality in large randomized controlled trials has been inconsistent or inconclusive but, in contrast to conventional inotropes, there have been no indications of worsened survival and some signals of improved heart failure-related quality of life. For this reason, levosimendan has been proposed as a safer inodilator option than traditional agents in settings, such as advanced heart failure. Positive effects of levosimendan on renal function have also been described. At the HEART FAILURE 2018 congress of the Heart Failure Association of the European Society of Cardiology, safe and effective use levosimendan in acute and advanced heart failure was examined in a series of expert tutorials. The proceedings of those tutorials are summarized in this review, with special reference to advanced heart failure and heart failure with concomitant renal dysfunction. Meta-analysis of clinical trials data is supportive of a renal-protective effect of levosimendan, while physiological observations suggest that this effect is exerted at least in part via organ-specific effects that may include selective vasodilation of glomerular afferent arterioles and increased renal blood flow, with no compromise of renal oxygenation. These lines of evidence require further investigation and their clinical significance needs to be evaluated in specifically designed prospective trials.
  • Thorlacius, Elin M.; Wåhlander, Håkan; Ojala, Tiina; Ylänen, Kaisa; Keski-Nisula, Juho; Synnergren, Mats; Romlin, Birgitta S.; Ricksten, Sven-Erik; Castellheim, Albert (2020)
    Objective : We aimed to determine the differential effects of intra-operative administration of milrinone versus levosimendan on myocardial function after pediatric cardiac surgery. Transthoracic echocardiography was employed for myocardial function evaluation, utilizing biventricular longitudinal strain with two-dimensional speckle tracking echocardiography in addition to conventional echocardiographic variables. Design : A secondary analysis of a randomized, prospective, double-blinded clinical drug trial Setting : Two pediatric tertiary university hospitals Participants : Infants between 1-12 months of age diagnosed with ventricular septal defect, complete atrioventricular septal defect, or tetralogy of Fallot who were scheduled for corrective surgery with cardiopulmonary bypass. Interventions : The patients were randomized to receive an infusion of milrinone or levosimendan at the start of cardiopulmonary bypass and for 26 consecutive hours. Measurements and main results : Biventricular longitudinal strain and conventional echocardiographic variables were measured preoperatively, on the first postoperative morning and prior to hospital discharge. The association between perioperative parameters and postoperative myocardial function was also investigated. Images were analyzed for left ventricular (n=67) and right ventricular (n=44) function. The day after surgery, left ventricular longitudinal strain was deteriorated in both the milrinone and levosimendan groups; 33% and 39%, respectively. The difference was not significant. The corresponding deterioration in right ventricular longitudinal strain was 42% and 50% (non-significant difference). For both groups, biventricular longitudinal strain approached their preoperative values at hospital discharge. Preoperative N-terminal pro-brain natriuretic peptide could predict the left ventricular strain on postoperative day one (p=0.014). Conclusions : Levosimendan was comparable to milrinone for left and right ventricular inotropic support in pediatric cardiac surgery.
  • Maack, Christoph; Eschenhagen, Thomas; Hamdani, Nazha; Heinzel, Frank R.; Lyon, Alexander R.; Manstein, Dietmar J.; Metzger, Joseph; Papp, Zoltan; Tocchetti, Carlo G.; Yilmaz, M. Birhan; Anker, Stefan D.; Balligand, Jean-Luc; Bauersachs, Johann; Brutsaert, Dirk; Carrier, Lucie; Chlopicki, Stefan; Cleland, John G.; de Boer, Rudolf A.; Dietl, Alexander; Fischmeister, Rodolphe; Harjola, Veli-Pekka; Heymans, Stephane; Hilfiker-Kleiner, Denise; Holzmeister, Johannes; de Keulenaer, Gilles; Limongelli, Giuseppe; Linke, Wolfgang A.; Lund, Lars H.; Masip, Josep; Metra, Marco; Mueller, Christian; Pieske, Burkert; Ponikowski, Piotr; Ristic, Arsen; Ruschitzka, Frank; Seferovic, Petar M.; Skouri, Hadi; Zimmermann, Wolfram H.; Mebazaa, Alexandre (2019)
    Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.