Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure.

ABSTRACT

AIMS: To determine the duration of haemodynamic and neurohormonal action of a 24-h infusion of levosimendan in heart failure. METHODS AND 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.