Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure

Mara T. Slawsky, Wilson S. Colucci, Stephen S. Gottlieb, Barry H. Greenberg, Ernest Haeusslein, Joshua Hare, Steven Hutchins, Carl V. Leier, Thierry H. Le Jemtel, Evan Loh, John Nicklas, David Ogilby, Bramah N. Singh, William Smith

Research output: Contribution to journalArticle

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Abstract

Background - We determined the short-term hemodynamic and clinical effects of levosimendan, a novel calcium-sensitizing agent, in patients with decompensated heart failure. Methods and Results - One hundred forty-six patients with New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21±1%) who had a pulmonary capillary wedge pressure ≥15 mm Hg and a cardiac index ≤2.5 L · min-1 · m-2 were enrolled in a multicenter, double-blind, placebo-controlled study and randomized 2:1 to intravenous infusion of levosimendan or placebo. Drug infusions were uptitrated over 4 hours from an initial infusion rate of 0.1 μg · kg-1 · min-1 to a maximum rate of 0.4 μg · kg-1 · min-1 and maintained at the maximal tolerated infusion rate for an additional 2 hours. Levosimendan caused dose-dependent increases in stroke volume and cardiac index beginning with the lowest infusion rate and achieving maximal increases in stroke volume and cardiac index of 28% and 39%, respectively. Heart rate increased modestly (8%) at the maximal infusion rate and was not increased at the 2 lowest infusion rates. Levosimendan caused dose-dependent decreases in pulmonary capillary wedge, fight atrial, pulmonary arterial, and mean arterial pressures. Levosimendan appeared to improve dyspnea and fatigue, as assessed by the patient and physician, and was not associated with a significant increase in adverse events. Conclusions - Levosimendan caused rapid dose-dependent improvement in hemodynamic function in patients with decompensated heart failure. These hemodynamic effects appeared to be accompanied by symptom improvement and were not associated with a significant increase in the number of adverse events. Levosimendan may be of value in the short-term management of patients with decompensated heart failure.

Original languageEnglish (US)
Pages (from-to)2222-2227
Number of pages6
JournalCirculation
Volume102
Issue number18
DOIs
StatePublished - Oct 31 2000

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Heart Failure
Hemodynamics
Stroke Volume
Placebos
Lung
Pulmonary Wedge Pressure
Proxy
simendan
Intravenous Infusions
Dyspnea
Fatigue
Arterial Pressure
Heart Rate
Calcium
Physicians
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Slawsky, M. T., Colucci, W. S., Gottlieb, S. S., Greenberg, B. H., Haeusslein, E., Hare, J., ... Smith, W. (2000). Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation, 102(18), 2222-2227. https://doi.org/10.1161/01.CIR.102.18.2222

Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. / Slawsky, Mara T.; Colucci, Wilson S.; Gottlieb, Stephen S.; Greenberg, Barry H.; Haeusslein, Ernest; Hare, Joshua; Hutchins, Steven; Leier, Carl V.; Le Jemtel, Thierry H.; Loh, Evan; Nicklas, John; Ogilby, David; Singh, Bramah N.; Smith, William.

In: Circulation, Vol. 102, No. 18, 31.10.2000, p. 2222-2227.

Research output: Contribution to journalArticle

Slawsky, MT, Colucci, WS, Gottlieb, SS, Greenberg, BH, Haeusslein, E, Hare, J, Hutchins, S, Leier, CV, Le Jemtel, TH, Loh, E, Nicklas, J, Ogilby, D, Singh, BN & Smith, W 2000, 'Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure', Circulation, vol. 102, no. 18, pp. 2222-2227. https://doi.org/10.1161/01.CIR.102.18.2222
Slawsky MT, Colucci WS, Gottlieb SS, Greenberg BH, Haeusslein E, Hare J et al. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation. 2000 Oct 31;102(18):2222-2227. https://doi.org/10.1161/01.CIR.102.18.2222
Slawsky, Mara T. ; Colucci, Wilson S. ; Gottlieb, Stephen S. ; Greenberg, Barry H. ; Haeusslein, Ernest ; Hare, Joshua ; Hutchins, Steven ; Leier, Carl V. ; Le Jemtel, Thierry H. ; Loh, Evan ; Nicklas, John ; Ogilby, David ; Singh, Bramah N. ; Smith, William. / Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. In: Circulation. 2000 ; Vol. 102, No. 18. pp. 2222-2227.
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abstract = "Background - We determined the short-term hemodynamic and clinical effects of levosimendan, a novel calcium-sensitizing agent, in patients with decompensated heart failure. Methods and Results - One hundred forty-six patients with New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21±1{\%}) who had a pulmonary capillary wedge pressure ≥15 mm Hg and a cardiac index ≤2.5 L · min-1 · m-2 were enrolled in a multicenter, double-blind, placebo-controlled study and randomized 2:1 to intravenous infusion of levosimendan or placebo. Drug infusions were uptitrated over 4 hours from an initial infusion rate of 0.1 μg · kg-1 · min-1 to a maximum rate of 0.4 μg · kg-1 · min-1 and maintained at the maximal tolerated infusion rate for an additional 2 hours. Levosimendan caused dose-dependent increases in stroke volume and cardiac index beginning with the lowest infusion rate and achieving maximal increases in stroke volume and cardiac index of 28{\%} and 39{\%}, respectively. Heart rate increased modestly (8{\%}) at the maximal infusion rate and was not increased at the 2 lowest infusion rates. Levosimendan caused dose-dependent decreases in pulmonary capillary wedge, fight atrial, pulmonary arterial, and mean arterial pressures. Levosimendan appeared to improve dyspnea and fatigue, as assessed by the patient and physician, and was not associated with a significant increase in adverse events. Conclusions - Levosimendan caused rapid dose-dependent improvement in hemodynamic function in patients with decompensated heart failure. These hemodynamic effects appeared to be accompanied by symptom improvement and were not associated with a significant increase in the number of adverse events. Levosimendan may be of value in the short-term management of patients with decompensated heart failure.",
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AU - Slawsky, Mara T.

AU - Colucci, Wilson S.

AU - Gottlieb, Stephen S.

AU - Greenberg, Barry H.

AU - Haeusslein, Ernest

AU - Hare, Joshua

AU - Hutchins, Steven

AU - Leier, Carl V.

AU - Le Jemtel, Thierry H.

AU - Loh, Evan

AU - Nicklas, John

AU - Ogilby, David

AU - Singh, Bramah N.

AU - Smith, William

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N2 - Background - We determined the short-term hemodynamic and clinical effects of levosimendan, a novel calcium-sensitizing agent, in patients with decompensated heart failure. Methods and Results - One hundred forty-six patients with New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21±1%) who had a pulmonary capillary wedge pressure ≥15 mm Hg and a cardiac index ≤2.5 L · min-1 · m-2 were enrolled in a multicenter, double-blind, placebo-controlled study and randomized 2:1 to intravenous infusion of levosimendan or placebo. Drug infusions were uptitrated over 4 hours from an initial infusion rate of 0.1 μg · kg-1 · min-1 to a maximum rate of 0.4 μg · kg-1 · min-1 and maintained at the maximal tolerated infusion rate for an additional 2 hours. Levosimendan caused dose-dependent increases in stroke volume and cardiac index beginning with the lowest infusion rate and achieving maximal increases in stroke volume and cardiac index of 28% and 39%, respectively. Heart rate increased modestly (8%) at the maximal infusion rate and was not increased at the 2 lowest infusion rates. Levosimendan caused dose-dependent decreases in pulmonary capillary wedge, fight atrial, pulmonary arterial, and mean arterial pressures. Levosimendan appeared to improve dyspnea and fatigue, as assessed by the patient and physician, and was not associated with a significant increase in adverse events. Conclusions - Levosimendan caused rapid dose-dependent improvement in hemodynamic function in patients with decompensated heart failure. These hemodynamic effects appeared to be accompanied by symptom improvement and were not associated with a significant increase in the number of adverse events. Levosimendan may be of value in the short-term management of patients with decompensated heart failure.

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