Effects of levosimendan on coronary artery flow and cardiac performance in patients with advanced heart failure.
BACKGROUND
Levosimendan has inotropic and vasodilatory effects. We investigated the effects of levosimendan on coronary flow and associated changes in neurohormonal activation and cardiac performance in patients with advanced heart failure.


METHODS
Forty-two patients with NYHA III-IV and a left ventricular ejection fraction (EF) 25+/-6%, were randomised to levosimendan 0.1 microg/kg/min (n=21) or placebo for 24 h. Before and 24 h after each treatment, we assessed: the maximal velocity (Vmax), time integral (VTI) and deceleration time (DT) of the diastolic coronary flow wave (CF) in LAD using transthoracic Doppler echocardiography, pulmonary artery systolic pressure by Doppler echocardiography, E/E' ratio using Doppler imaging of mitral inflow velocity, tissue Doppler imaging of the mitral annulus and B-type natriuretic peptide (BNP) levels.


RESULTS
By ANOVA, there was a greater increase in CF-Vmax (43+/-23 vs.25+/-8 cm/s), CF-DT (904+/-250 vs. 667+/-151 ms), and EF and a greater decrease in BNP, pulmonary artery systolic pressure and E/E? after levosimendan than after placebo (p<0.05). Compared to baseline, the percent changes in CF-VTI were related to the concomitant changes in EF, E/E?, and BNP after treatment with levosimendan (r=0.69, r=?0.51 and r=?0.80, p<0.05 respectively).


CONCLUSIONS
Treatment with levosimendan improves coronary flow and microcirculation in parallel with an improvement in cardiac performance and neurohormonal activation in patients with advanced heart failure.
Second Cardiology Department and Heart Failure Unit, University of Athens Medical School, Attikon University Hospital, Athens, Greece. ignoik@otenet.gr
Ignatios
I
Ikonomidis
John T
JT
Parissis
Ioannis
I
Paraskevaidis
Kallirrhoe
K
Kourea
Vasiliki
V
Bistola
John
J
Lekakis
Gerasimos
G
Filippatos
Dimitrios Th
DT
Kremastinos
D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D015150:Echocardiography, Doppler; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011724:Pyridazines / Q000008:administration & dosage*; D012039:Regional Blood Flow / Q000187:drug effects*; D000077464:Simendan; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan