The effectiveness of levosimendan on veno-arterial extracorporeal membrane oxygenation management and outcome: a systematic review and meta-analysis,

We sought to synthesize the available evidence regarding safety and efficacy of intermittent levosimendan (LEVO) infusions in ambulatory patients with end-stage heart failure (HF). Safety and efficacy of ambulatory intermittent LEVO infusion in patients with end-stage HF are yet not established. We systematically searched MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane databases, from inception to January 30, 2021 for studies reporting outcome of adult ambulatory patients with end-stage HF treated with intermittent LEVO infusion. Fifteen studies (8 randomized and 7 observational) comprised 984 patients (LEVO [N = 727] and controls [N = 257]) met the inclusion criteria. LEVO was associated with improved New York Heart Association (NYHA) functional class (weighted mean difference [WMD] −1.04, 95%CI: −1.70 to −0.38, p < 0.001, 5 studies, I2 = 93%), improved left ventricular (LV) ejection fraction (WMD 4.0%, 95%CI: 2.8% to 5.3%, p < 0.001, 6 studies, I2 = 9%), and reduced BNP levels (WMD −549 pg/mL, 95%CI −866 to −233, p < 0001, 3 studies, I2 = 66%). All-cause death was not different (RR 0.65, 95%CI: 0.38 to 1.093, p = 0.10, 6 studies, I2 = 0), but cardiovascular death was lower on LEVO (RR 0.34, 95%CI: 0.13 to 0.87, p = 0.02, 3 studies, I2 = 0) compared to controls. Furthermore, health-related quality of life (HRQoL) was improved alongside with reduced LV size following LEVO infusions. Major adverse events were not different between LEVO and placebo. In conclusion, intermittent LEVO infusions in ambulatory patients with end-stage HF is associated with less frequent cardiovascular death alongside with improved NYHA class, quality of life, BNP levels, and LV function. However, the current evidence is limited by heterogeneous and relatively small studies.

Left ventricular assist device (LVAD) therapy has been instrumental in saving lives of patients with end-stage heart failure (HF). Recent generation devices have short-to-mid-term survival rates close to heart transplantation. Unfortunately, up to 1 in 4 patients develop a life-threatening right-sided HF (RHF) early post LVAD implantation, with high morbidity and mortality rate, necessitating prolonged ICU stay, prolonged inotropic support, and implantation of a right-ventricular assist device. Pre-operative optimization of HF therapy could help in prevention, and/or mitigation of RHF. Levosimendan (LEVO) is a non-conventional inotropic agent that works by amplifying calcium sensitivity of troponin C in cardiac myocytes, without increasing the intra-cellular calcium or exacerbating ischemia. LEVO acts as an inodilator, which reduces the cardiac pre-, and after-load. LEVO administration is associated with hemodynamic improvements. Despite decades long of the use of LVAD and more than two decades of the use of LEVO for HF, the literature on LEVO use in LVAD is very limited. In this paper, we sought to conduct a systematic review to synthesize evidence related to the use of LEVO for the mitigation and/or prevention of RHF in patients undergoing LVAD implantation.

Acute right-sided heart failure (RHF) is a complex clinical syndrome, with a wide range of clinical presentations, associated with increased mortality and morbidity, but about which there is a scarcity of evidence-based literature. A temporary right-ventricular assist device (t-RVAD) is a potential treatment option for selected patients with severe right-ventricular dysfunction as a bridge-to-recovery or as a permanent solution. We sought to conduct a systematic review to determine the safety and efficacy of t-RVAD implantation. Thirty-one studies met the inclusion criteria, from which data were extracted. Successful t-RVAD weaning ranged between 23% and 100%. Moreover, 30-day survival post-temporary RAVD implantation ranged from 46% to 100%. Bleeding, acute kidney injury, stroke, and device malfunction were the most commonly reported complications. Notwithstanding this, t-RVAD is a lifesaving option for patients with severe RHF, but the evidence stems from small non-randomized heterogeneous studies utilizing a variety of devices. Both the etiology of RHF and time of intervention might play a major role in determining the t-RVAD outcome. Standardized endpoints definitions, design and methodology for t-RVAD trials is needed. Furthermore, efforts should continue in improving the technology as well as improving the timely provision of a t-RVAD.