Myocardial efficiency during levosimendan infusion in congestive heart failure.
OBJECTIVE
Levosimendan, a novel calcium-dependent calcium sensitizer of the myocardial contractile proteins, also enhances diastolic relaxation and induces peripheral vasodilation by opening potassium channels. To assess the combined energetical effects of levosimendan infusion in vivo, we performed positron emission tomography in patients with decompensated chronic heart failure.


RESULTS
Eight hospitalized patients with New York Heart Association functional class III or IV heart failure received levosimendan or placebo intravenously in a randomized double-blind cross-over study. During steady-state, dynamic positron emission tomography with [11C]acetate was used to assess myocardial oxygen consumption and [15O]H2O to measure myocardial blood flow. Cardiac performance and dimensions were assessed by pulmonary artery catheterization and echocardiography. Compared with healthy volunteers, myocardial oxygen consumption during placebo was elevated in the right ventricle but comparable in the left ventricle. During administration of levosimendan, cardiac output increased by 32% (P = .002) mainly because of higher stroke volume. Coronary, pulmonary, and systemic vascular resistance values were significantly reduced. Mean myocardial blood flow increased from 0.76 to 1.02 mL/min/g (P = .033). Levosimendan was neutral on myocardial oxygen consumption and left ventricular efficiency, but it improved right ventricular mechanical efficiency by 24% (P = .012).


CONCLUSIONS
Levosimendan has an energetically favorable short-term profile in the treatment of congestive heart failure. It enhances cardiac output without oxygen wasting, particularly by improving efficiency in the right ventricle.
Ukkonen
H
H
Department of Medicine, Turku University Hospital and Turku PET Centre, Finland.
Saraste
M
M
Akkila
J
J
Knuuti
J
J
Karanko
M
M
Iida
H
H
Lehikoinen
P
P
Någren
K
K
Lehtonen
L
L
Voipio-Pulkki
L M
LM
D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002407:Catheterization, Swan-Ganz; D003331:Coronary Vessels / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D011724:Pyridazines / Q000008:administration & dosage / Q000627:therapeutic use*; D000077464:Simendan; D014055:Tomography, Emission-Computed; D014463:Ultrasonography
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan