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Abstract
Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.
Keywords
DECOMPENSATED HEART-FAILURE, IMPROVES RENAL-FUNCTION, AMYOTROPHIC-LATERAL-SCLEROSIS, RIGHT-VENTRICULAR FUNCTION, CARDIAC, TROPONIN-C, EXTRACORPOREAL MEMBRANE-OXYGENATION, GLOMERULAR-FILTRATION-RATE, CALCIUM SENSITIZING DRUG, CORONARY, BLOOD-FLOW, ARTERY-BYPASS GRAFT, acute heart failure, advanced heart failure, hemodynamics, inodilator, inotrope, neurohormone, regulatory clinical trial

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MLA
Papp, Zoltan, et al. “Levosimendan Efficacy and Safety : 20 Years of SIMDAX in Clinical Use.” JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 76, no. 1, Lippincott Williams & Wilkins, 2020, pp. 4–22, doi:10.1097/FJC.0000000000000859.
APA
Papp, Z., Agostoni, P., Alvarez, J., Bettex, D., Bouchez, S., Brito, D., … Pollesello, P. (2020). Levosimendan efficacy and safety : 20 years of SIMDAX in clinical use. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 76(1), 4–22. https://doi.org/10.1097/FJC.0000000000000859
Chicago author-date
Papp, Zoltan, Piergiuseppe Agostoni, Julian Alvarez, Dominique Bettex, Stefaan Bouchez, Dulce Brito, Vladimir Cerny, et al. 2020. “Levosimendan Efficacy and Safety : 20 Years of SIMDAX in Clinical Use.” JOURNAL OF CARDIOVASCULAR PHARMACOLOGY 76 (1): 4–22. https://doi.org/10.1097/FJC.0000000000000859.
Chicago author-date (all authors)
Papp, Zoltan, Piergiuseppe Agostoni, Julian Alvarez, Dominique Bettex, Stefaan Bouchez, Dulce Brito, Vladimir Cerny, Josep Comin-Colet, Marisa G. Crespo-Leiro, Juan F. Delgado, Istvan Edes, Alexander A. Eremenko, Dimitrios Farmakis, Francesco Fedele, Candida Fonseca, Sonja Fruhwald, Massimo Girardis, Fabio Guarracino, Veli-Pekka Harjola, Matthias Heringlake, Antoine Herpain, Leo M. A. Heunks, Tryggve Husebye, Visnja Ivancan, Kristjan Karason, Sundeep Kaul, Matti Kivikko, Janek Kubica, Josep Masip, Simon Matskeplishvili, Alexandre Mebazaa, Markku S. Nieminen, Fabrizio Oliva, Julius G. Papp, John Parissis, Alexander Parkhomenko, Pentti Poder, Gerhard Poelzl, Alexander Reinecke, Sven-Erik Ricksten, Hynek Riha, Alain Rudiger, Toni Sarapohja, Robert H. G. Schwinger, Wolfgang Toller, Luigi Tritapepe, Carsten Tschoepe, Gerhard Wikstroem, Dirk von Lewinski, Bojan Vrtovec, and Piero Pollesello. 2020. “Levosimendan Efficacy and Safety : 20 Years of SIMDAX in Clinical Use.” JOURNAL OF CARDIOVASCULAR PHARMACOLOGY 76 (1): 4–22. doi:10.1097/FJC.0000000000000859.
Vancouver
1.
Papp Z, Agostoni P, Alvarez J, Bettex D, Bouchez S, Brito D, et al. Levosimendan efficacy and safety : 20 years of SIMDAX in clinical use. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. 2020;76(1):4–22.
IEEE
[1]
Z. Papp et al., “Levosimendan efficacy and safety : 20 years of SIMDAX in clinical use,” JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 76, no. 1, pp. 4–22, 2020.
@article{8676077,
  abstract     = {Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.},
  author       = {Papp, Zoltan and Agostoni, Piergiuseppe and Alvarez, Julian and Bettex, Dominique and Bouchez, Stefaan and Brito, Dulce and Cerny, Vladimir and Comin-Colet, Josep and Crespo-Leiro, Marisa G. and Delgado, Juan F. and Edes, Istvan and Eremenko, Alexander A. and Farmakis, Dimitrios and Fedele, Francesco and Fonseca, Candida and Fruhwald, Sonja and Girardis, Massimo and Guarracino, Fabio and Harjola, Veli-Pekka and Heringlake, Matthias and Herpain, Antoine and Heunks, Leo M. A. and Husebye, Tryggve and Ivancan, Visnja and Karason, Kristjan and Kaul, Sundeep and Kivikko, Matti and Kubica, Janek and Masip, Josep and Matskeplishvili, Simon and Mebazaa, Alexandre and Nieminen, Markku S. and Oliva, Fabrizio and Papp, Julius G. and Parissis, John and Parkhomenko, Alexander and Poder, Pentti and Poelzl, Gerhard and Reinecke, Alexander and Ricksten, Sven-Erik and Riha, Hynek and Rudiger, Alain and Sarapohja, Toni and Schwinger, Robert H. G. and Toller, Wolfgang and Tritapepe, Luigi and Tschoepe, Carsten and Wikstroem, Gerhard and von Lewinski, Dirk and Vrtovec, Bojan and Pollesello, Piero},
  issn         = {0160-2446},
  journal      = {JOURNAL OF CARDIOVASCULAR PHARMACOLOGY},
  keywords     = {DECOMPENSATED HEART-FAILURE,IMPROVES RENAL-FUNCTION,AMYOTROPHIC-LATERAL-SCLEROSIS,RIGHT-VENTRICULAR FUNCTION,CARDIAC,TROPONIN-C,EXTRACORPOREAL MEMBRANE-OXYGENATION,GLOMERULAR-FILTRATION-RATE,CALCIUM SENSITIZING DRUG,CORONARY,BLOOD-FLOW,ARTERY-BYPASS GRAFT,acute heart failure,advanced heart failure,hemodynamics,inodilator,inotrope,neurohormone,regulatory clinical trial},
  language     = {eng},
  number       = {1},
  pages        = {4--22},
  publisher    = {Lippincott Williams & Wilkins},
  title        = {Levosimendan efficacy and safety : 20 years of SIMDAX in clinical use},
  url          = {http://dx.doi.org/10.1097/FJC.0000000000000859},
  volume       = {76},
  year         = {2020},
}

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