The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine

Aim: To investigate the effect of a new inotropic drug, levosimendan compared with dobutamine on levels of brain natriuretic peptide (BNP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and malondialdehyde (MDA) in patients with severe decompensated heart failure. Methods and results: Twenty-nine consecutive patients (22 males and 7 females), mean age 70.5 +/- 9.9 years, with decompensated heart failure on standard medical therapy, were randomised to receive either a 24 h infusion of levosimendan (n = 15) or dobutamine (n = 14). Blood samples were drawn at baseline, 48 h and 5 days post infusion. Levosimendan produced a significant reduction in BNP compared to baseline, at both 48 h (744.1 +/- 100 vs 1136.3 +/- 93.7 pg/ml, p =0.04) and 5 days (446 +/- 119.3 vs 1136.3 +/- 93.7 pg/ml, p =0.03), while IL-6 values decreased after 5 days (4.8 +/- 1.3 vs 8.6 +/- 1.5 pg/ml, p = 0.01). MDA levels were significantly lower 5 days after levosimendan compared to baseline (2.3 +/- 0.2 vs 3 +/- 0.3 mu M, p = 0.01). TNF-alpha levels did not differ between the groups. The comparison of percentage alteration compared to baseline showed that BNP (-44.5 +/- 7.6% vs 4.8 +/- 18.7%, p = 0.025), MDA (-21.8 +/- 5.1% vs 14.9 +/- 8.5%, p = 0.001) and IL-6 (-38.8 +/- 12.5% vs 70.2 +/- 24%, p = 0.001) levels were significantly lower in the levosimendan group 5 days after treatment compared to the dobutamine group. Conclusions: Treatment with levosimendan in advanced decompensated heart failure exerts a beneficial hemodynamic, anti-inflammatory and antioxidant effect. These findings may give an insight into the favourable impact on mortality that levosimendan appears to have in published multicenter trials. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.