Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure.
OBJECTIVE
To determine the duration of haemodynamic and neurohormonal action of a 24-h infusion of levosimendan in heart failure.


RESULTS
This was a double-blind, parallel group study in patients with New York Heart Association class II to IV heart failure. Twenty-two patients, with left ventricular ejection fraction <35% and pulmonary capillary wedge pressure (PCWP) above 12 mmHg, were randomised to receive either levosimendan (12 microg/kg followed by a continuous infusion of 0.1-0.2 microg/min) or placebo. Invasively measured cardiac output (CO) increased from 4.3 l/min to 5.4 l/min in the levosimendan group at 6 h. PCWP decreased from 20 mmHg to 15 mmHg in response to levosimendan. Echocardiographically measured maximal effect on PCWP occurred after 6 h, whereas CO reached its highest value at 24 h. The estimated duration of the decrease in PCWP was 7-9 days, and in CO was 12-13 days. Plasma NT-proANP and NT-proBNP levels reached their lowest values at days 3 and 2, and the treatment effect was estimated to last 16 and 12 days, respectively. The long-acting haemodynamic responses reflect levels of the active metabolites OR-1896 and OR-1855, maximal metabolite levels occurred at day 3.


CONCLUSIONS
Levosimendan infusion achieved a rapid improvement in haemodynamic parameters in patients with congestive heart failure with maximal effects occurring 1-3 days after starting the infusion, effects were sustained for up to at least a week.
Lilleberg
J
J
Division of Cardiology, Helsinki University Central Hospital, Haartmaninkatu 4, SF-00290 Helsinki, Finland.
Laine
M
M
Palkama
T
T
Kivikko
M
M
Pohjanjousi
P
P
Kupari
M
M
D009320:Atrial Natriuretic Factor / Q000097:blood; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010919:Placebos; D011652:Pulmonary Circulation / Q000187:drug effects; D011724:Pyridazines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D000077464:Simendan; D013599:Systole / Q000187:drug effects*; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
D002316:Cardiotonic Agents; D006835:Hydrazones; D010446:Peptide Fragments; D010919:Placebos; D011724:Pyridazines; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000077464:Simendan; D009320:Atrial Natriuretic Factor