Long-term effects of levosimendan infusion on inflammatory processes and sFas in patients with severe heart failure

Abstract: Background: The calcium sensitizer levosimendan improves myocardial contractility in patients with heart failure, although its effects on inflammation and apoptosis are unknown. Aim: To examine the effects of levosimendan on markers of inflammation and apoptosis, over a period of 30 d following a 24 h infusion, in patients with heart failure. Methods: Thirty four patients with severe heart failure were randomised to receive a 24 h infusion of levosimendan or placebo, in a double-blind trial. Haemodynamic evaluation and blood sampling were performed at baseline, 24 h, 30 h, 48 h, 7 d and 30 d after the end of the infusion. Results: Seven patients (1 levosimendan, 6 placebo), were excluded during follow-up. In the remaining 27 patients, levosimendan decreased serum IL-6 and sFAS, 24 h after the infusion (p <0.01 and p <0.05 vs baseline), an effect sustained for 7–30 d. Serum TNF-α and sTNF-R1 were decreased between 48 h (p <0.01 vs baseline for both) and 7 d (p <0.05 vs baseline for sTNF-R1) after infusion. Serum sTNF-R2 was decreased at 24 h (p <0.05 vs baseline) and remained lower than baseline for at least 7 d (p <0.05). Conclusions: These findings indicate that levosimendan decreases the expression of proinflammatory cytokines, TNF-α receptors and sFAS, immediately after infusion, an effect which persists for 7–30 d. [Copyright &y& Elsevier]