(Circulation. 2000;102:2222.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Acute Hemodynamic and Clinical Effects of Levosimendan in Patients With Severe Heart Failure
From the Cardiomyopathy Program and Cardiovascular Medicine Section, Boston University Medical Center (W.S.C.) and VA Boston Healthcare System (M.T.S.), Boston, Mass; University of Maryland (S.S.G.), Baltimore, Md; University of California (B.H.G.), San Diego; California Pacific Medical Center (E.H.), San Francisco; Johns Hopkins Hospital (J.H.), Baltimore, Md; Cardiology Consultants (S.H.), Little Rock, Ark; Ohio State University (C.V.L.), Columbus; Albert Einstein College of Medicine (T.H.L.), Bronx, NY; University of Pennsylvania Medical Center (E.L.), Philadelphia; University of Michigan Hospital (J.N.), Ann Arbor; Presbyterian University of Pennsylvania Medical Center (D.O.), Philadelphia; West Los Angeles VA Medical Center (B.N.S.), Los Angeles, Calif; and Louisiana Cardiovascular Research Center (W.S.), New Orleans.
Correspondence to Wilson S. Colucci, MD, Cardiovascular Section, Boston University Medical Center, 88 E Newton St, Boston, MA 02118. E-mail wilson.colucci{at}bmc.org
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, right 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.
Key Words: heart failure • inotropic agents • vasodilation • calcium
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