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Endothelial dysfunction (ED) is frequently found in patients with heart failure (HF). Among several pharmacological agents reported to improve endothelial function, levosimendan seems to be a promising one, even though, to date, only two previously published studies have evaluated its effects on ED in these patients. The aim of our pilot study was to further investigate the role of periodic levosimendan infusion on endothelial function in patients affected by advanced HF. In this cross-sectional study, three different groups were enrolled: 20 patients with advanced HF treated with periodic levosimendan (LEVO), 20 patients with HF on optimal medical therapy (OMT), and 20 healthy subjects (control group). ED was evaluated through flow-mediated dilation (FMD) at the level of the brachial artery. The three groups presented similar ages with significant differences in gender distribution, systolic blood pressure, and chronic kidney disease (eGFR < 30 mL/min). In HF patients, ischaemic aetiology was more prevalent in the LEVO group than in the OMT group (60 vs. 40%, p < 0.001). The New York Heart Association (NYHA) functional class was worse in the LEVO group, as well as in NT-proBNP (5636.7 ± 6164.6 ng/dL and 1243.7 ± 1487.2 ng/dL, in the LEVO and OMT groups, respectively, p = 0.005). The FMD was significantly higher in the healthy control group compared to that of the OMT group (15.7 ± 6.4 vs. 9.1 ± 6.0%, p = 0.007) while it showed an intermediate value in LEVO patients (12.4 ± 7.1%) (ANOVA p = 0.010). In conclusion, levosimendan therapy seems to ameliorate endothelial dysfunction related to heart failure. Longitudinal studies in patients on periodic therapy are needed in order to confirm the long-term effects of levosimendan on ED.

Introduction: Endothelial dysfunction (ED) of peripheral arteries in chronic heart failure (CHF) subjects has been demonstrated. We assessed endothelial function in subjects undergoing unconventional treatments for CHF, namely heart transplantation (HTX), continuous-flow left ventricular assist device implantation (LVAD), and repeated levosimendan infusions (r-LEVO). Methods: Twenty HTX recipients (median time from HTX 21 months), 20 patients supported with LVAD (median time from implant 39 months), and 20 patients receiving monthly Levosimendan infusions (median time on treatment 28 months) were enrolled and compared to a group of 20 healthy subjects. ED was evaluated with ultrasound assessment of the diameter before and after ischemic stress at the brachial artery level. The difference between the two diameters normalized for the baseline value (flow mediated dilation–FMD) has been used for the analysis. All the patients were stable at the time of FMD assessment, with those on r-LEVO being evaluated prior to infusion. Results: FMD was significantly lower in HTX and LVAD groups with respect to controls (9.8 ± 7.4, 9.3 ± 5.7, and 15.6 ± 6.4% respectively, p = 0.01), but not in r-LEVO group (12.5 ± 6.9%). When patients were analysed according to time from the operation or on treatment, (