https://orcid.org/0000-0001-6994-768X
Figures & data
Figure 1. An overview of the pleiotropic actions of levosimendan. Levosimendan acts as an inotrope by enhancing the calcium sensitivity of troponin C in heart muscle, thereby increasing the force of contraction and ensuring an enhancement of cardiac output, without a commensurate increase in the oxygen requirements of the heart. A similar action may occur in the slow skeletal muscle fibers, for instance in the diaphragm, that would be of help in weaning from ventilation or in delaying the need for ventilation in patients with amyotrophic lateral sclerosis. By opening adenosine triphosphate-sensitive potassium channels in the vascular smooth muscle cells of certain vessels, levosimendan causes vasodilation and a reduction in systemic vascular resistance (SVR), which is also seen as a decrease in pulmonary capillary wedge pressure (PCWP), and ensuring an enhancement of cardiac output, in addition to its inotropic actions. A similar action on mitochondrial and sarcolemmal KATP channels in cardiac myocytes is linked to cardioprotection. Finally, the preferential vasodilation achieved by levosimendan on afferent versus efferent glomerular arterioles increases the glomerular filtration rate (GFR) without increasing renal oxygen demand. (From Kurdi et al. [Citation33] with permission.)
![Figure 1. An overview of the pleiotropic actions of levosimendan. Levosimendan acts as an inotrope by enhancing the calcium sensitivity of troponin C in heart muscle, thereby increasing the force of contraction and ensuring an enhancement of cardiac output, without a commensurate increase in the oxygen requirements of the heart. A similar action may occur in the slow skeletal muscle fibers, for instance in the diaphragm, that would be of help in weaning from ventilation or in delaying the need for ventilation in patients with amyotrophic lateral sclerosis. By opening adenosine triphosphate-sensitive potassium channels in the vascular smooth muscle cells of certain vessels, levosimendan causes vasodilation and a reduction in systemic vascular resistance (SVR), which is also seen as a decrease in pulmonary capillary wedge pressure (PCWP), and ensuring an enhancement of cardiac output, in addition to its inotropic actions. A similar action on mitochondrial and sarcolemmal KATP channels in cardiac myocytes is linked to cardioprotection. Finally, the preferential vasodilation achieved by levosimendan on afferent versus efferent glomerular arterioles increases the glomerular filtration rate (GFR) without increasing renal oxygen demand. (From Kurdi et al. [Citation33] with permission.)](/cms/asset/98053f01-5b8b-44fc-8f4a-65edcff329c6/ierk_a_1905520_f0001_oc.jpg)
Figure 2. Meta-analysis of the effect of levosimendan on 31-day survival in the four phase III regulatory trials submitted to the authorities for the introduction of levosimendan as a treatment for acutely decompensated heart failure: LIDO (203 patients) [Citation47]; RUSSLAN (504 patients) [Citation48]; REVIVE 1 and 2 (700 patients) [Citation107]; and SURVIVE (1327 patients) [Citation117]. Pooled statistics were calculated using the Cochran–Mantel–Haenszel test, controlling for study. Total events in the pooled levosimendan arms were 167/1519 (11.0%) and total events in the pooled comparator arms were 145/1215 (11.9%). Odds ratio 0.81; 95% confidence interval 0.64–1.04
![Figure 2. Meta-analysis of the effect of levosimendan on 31-day survival in the four phase III regulatory trials submitted to the authorities for the introduction of levosimendan as a treatment for acutely decompensated heart failure: LIDO (203 patients) [Citation47]; RUSSLAN (504 patients) [Citation48]; REVIVE 1 and 2 (700 patients) [Citation107]; and SURVIVE (1327 patients) [Citation117]. Pooled statistics were calculated using the Cochran–Mantel–Haenszel test, controlling for study. Total events in the pooled levosimendan arms were 167/1519 (11.0%) and total events in the pooled comparator arms were 145/1215 (11.9%). Odds ratio 0.81; 95% confidence interval 0.64–1.04](/cms/asset/226ea751-e029-4348-ae36-b275f51bbc87/ierk_a_1905520_f0002_b.gif)
Figure 3. Relative (%) changes in glomerular filtration rate (GFR), renal blood flow (RBF), and cardiac index (CI), after administration of levosimendan (gray) versus dobutamine (white) in the randomized trial (32 patients) reported by Lannemyr et al. [Citation103]. Following treatment, the levosimendan and dobutamine groups displayed similar increases in CI and RBF with no significant differences between groups. In contrast, GFR increased by 22% in the levosimendan group but remained unchanged in the dobutamine group (p= 0.012). Filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine (p= 0.045)
![Figure 3. Relative (%) changes in glomerular filtration rate (GFR), renal blood flow (RBF), and cardiac index (CI), after administration of levosimendan (gray) versus dobutamine (white) in the randomized trial (32 patients) reported by Lannemyr et al. [Citation103]. Following treatment, the levosimendan and dobutamine groups displayed similar increases in CI and RBF with no significant differences between groups. In contrast, GFR increased by 22% in the levosimendan group but remained unchanged in the dobutamine group (p= 0.012). Filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine (p= 0.045)](/cms/asset/39dbc3a2-50f1-494a-8c46-acadb4aeba58/ierk_a_1905520_f0003_b.gif)