Patients with symptomatic advanced heart failure despite optimal medical treatment are sometimes unable to be discharged because they are dependent on dobutamine infusions that cannot be weaned off. Such patients are at high-risk of death and may be waiting for a heart transplantation or a long-term mechanical assist device or, in contrast, may not be eligible for these therapeutic options. In such situations, repetitive infusions of levosimendan may offer the advantage of a prolonged inotropic effect with the possibility of improving the clinical symptomatology and allowing hospital discharge. Very limited data exists regarding the effectiveness of repetitive infusions of levosimendan [
37‐
41]. A recent meta-analysis confirmed the potential usefulness of this approach, despite the heterogeneity of the existing studies [
42]. The LevoRep study was the first multicenter RCT evaluating the effect of 4 injections of levosimendan (0.2 μg kg
−1 min
−1) over 6 h at 2-week intervals in 120 advanced heart failure patients [
43]. The improvement in the 6-min walk test (primary outcome) was not significant, and the hazard ratio for the survival free of events was 0.50 (95% CI 0.25–1.05) favoring the group receiving levosimendan versus placebo (
p = 0.069). The LION-HEART study, another multicenter RCT involving 69 patients with chronic advanced heart failure, compared the effect of 6-h levosimendan infusions (0.2 μg kg
−1 min
−1) repeated every 2 weeks for 12 weeks with placebo infusions on NT-proBNP levels at 12 weeks [
44]. The authors observed that repetitive infusions of levosimendan significantly reduced the NT-proBNP, but also the readmission rate for acute heart failure at 12 months (20% versus 65%,
P < 0.001) and attenuated the decline in quality of life (20% versus 63%,
P = 0.022). The incidence of serious adverse events was not different between treatment and placebo groups, reflecting the safety of repetitive infusions of levosimendan. However, it is important to mention that although mortality and readmission rates decreased with levosimendan, they remained much higher in comparison to those observed when heart transplantation or mechanical circulatory assist devices could be carried out. Therefore, the strategy of repetitive infusions cannot be considered as an alternative to them, but alleviates the symptoms and improves the quality of life in patients awaiting transplantation or in those who are ineligible for more invasive approaches. A new RCT (LeoDOR, NCT03437226) is currently under way to try to confirm the usefulness of repeated infusions of levosimendan in this patient population [
45].