Acetylation status does not affect levosimendan's hemodynamic effects in heart failure patients.
OBJECTIVE
Levosimendan is indicated for acute heart failure. The formation of levosimendan's active metabolite OR-1896 is dependent on the acetylator status. We evaluated whether acetylator status affects the hemodynamic responses after levosimendan infusion.


METHODS
Forty-one NYHA III to IV heart failure patients were divided into rapid and slow acetylators by population kinetic modeling. Invasive hemodynamics and plasma concentrations of levosimendan and its metabolites were followed serially.


RESULTS
Fifty-six percent of the patients were rapid and 44% slow acetylators. Levosimendan induced increases in heart rate and cardiac output, and decreases in pulmonary capillary wedge pressure (PCWP) and blood pressure, which were sustained at 24 hours after stopping the infusion. At this time, levosimendan levels were undetectable, and OR-1896 levels were about two-fold higher in rapid acetylators. However, hemodynamic effects were similar; mean(SEM) change from baseline in cardiac output was +2.0(0.3) vs. +1.6(0.3) l/min (p = 0.309), and in PCWP -8(2) vs. -7(1) mmHg (p = 0.536), in rapid and slow acetylators, respectively.


CONCLUSIONS
The sustained hemodynamic effects of levosimendan are similar irrespective of acetylator status.
Helsinki University Central Hospital, Department of Cardiology, HUS, Helsinki, Finland. matti.kivikko@hus.fi
Matti
M
Kivikko
Stig
S
Sundberg
Mats O
MO
Karlsson
Pasi
P
Pohjanjousi
Wilson S
WS
Colucci
D000081:Acetamides / Q000097:blood; D000107:Acetylation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011724:Pyridazines / Q000097:blood / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000077464:Simendan; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000097:blood / Q000627:therapeutic use*
D000081:Acetamides; D006835:Hydrazones; C414222:N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan