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BackgroundLevosimendan improves clinical and hemodynamic parameters exerting an anti-inflammatory and antiapoptotic effect in decompensated heart failure. The aim of this study was to evaluate the effects of levosimendan on LV torsion, plasma levels of NT-proBNP and on the balance between pro-inflammatory (TNF-α, IL-6) and anti-inflammatory cytokines (IL-10).MethodsWe enrolled 24 patients (age 62 ± 7 years) with acute HF, NYHA class IV and severe LV dysfunction. All patients underwent transthoracic echocardiography using two-dimensional speckle tracking analysis to detect LV twist angle (LVTA), at baseline and 1 week after treatment with levosimendan infusion. Biochemical parameters (pro-BNP, IL-6, IL-10, TNF-α) were determined by enzyme-linked immunosorbent (ELISA).ResultsAfter one week, we observed an improvement in LV function especially in LVTA (4.15 ± 2.54 vs 2.9 ± 2.1 p < 0.01), in LV ejection fraction (27.3 ± 8.04 vs 21.6 ± 6.8 p = 0.03) and also a significant reduction in BNP levels (1844 ± 560 vs 4713 ± 1050, p = 0.03). The multiple linear regression analysis showed a significant relation between a reduction of TNF α/IL-10 ratio (Δ > 20%) and BNP (Δ > 40%), LVEF (Δ > 10%) and LVTA (Δ > 20%) (O.R. 1.77, 95% C.I. 1.11–2.83; O.R. 1.49, 95% C.I. 1.08–2.67; O.R. 1.66, 95% C.I. 1.10–2.74, respectively, confirmed p, all < 0.01 by Hosmer–Lemeshov confirmation and the formal test for interaction).ConclusionsLevosimendan exerts a hemodynamic effect by improving EF and LV torsion in patients with acute HF in association with a positive effect on the balance between pro and anti-inflammatory cytokines.

Statins are relevant drugs involved in the reduction of cardiovascular events both in primary and secondary prevention. Related muscular side-effects are the most common cause of withdrawal and statins discontinuation could induce a negative rebound effect in terms of vascular events. Among factors in association with statins side-effects the combination with other drugs and the female sex are established conditions. However recent data suggest a specific genetic influence in intolerance development, at least for some statins. Indeed a genome-wide study in patients treated with simvastatin found an impressive association between single-nucleotide polymorphisms (SNPs) located within SLCO1B1 gene on chromosome 12 and established myopathy. Furthermore, the association between the SLCO1B1*5 variant and side-effects was found also in patients treated with atorvastatin but not, apparently, with pravastatin and categorized as carriers of mild-myopathy. Recently a similar evidence has been suggested in type 2 diabetic patients treated mainly with simvastatin. However another relevant issue is that, apart from genetic influence in liver transporters influencing drug levels, the complexity of mechanisms involved in the muscular side effects of statins has been addressed by the evidence of other influencing pathways such as the variant within the COQ2 gene involved in Coenzyme Q(10) mild-asymptomatic deficiency and skeletal muscle drug transporters expression. In conclusion, the picture of putative pharmacogenetic modulation of statins safety is reaching a growing body of evidence for translation into clinical practice but more specific studies for each single statin, in different clinical settings, both from genome-wide or competitive candidate genes evaluation, are needed before describing a definitive class-risk profile.