Use Of Levosimendan Research Articles

Early-term results of early coronary artery bypass graft surgery in patients undergoing primary percutaneous coronary intervention due to acute coronary syndrome

Objectives: This study aimed to investigate the early results of the patients presented with acute coronary syndrome (ACS) who underwent coronary artery bypass grafting (CABG) after percutaneous coronary intervention (PCI) to the culprit lesion. Methods: Patients who underwent CABG between January 2011 and January 2014 were enrolled and divided into two groups. Group 1 (102 patients) was consist of the patients who were hospitalized with ACS and underwent CABG after a previous PCI. Group 2 (107 patients) was consisting of the patients who underwent elective CABG operation after elective coronary angiography. Results: There was no statistically significant difference between the groups in terms of demographic features and preoperative risk factors. Preoperative use of angiotensin-converting enzyme inhibitor and levosimendan were significantly higher in group 1 compared to group 2. (95 (93.1%) vs. 89 (83.1%), p = 0.027). The operative variables were similar between two groups whereas the postoperative blood drainage amounts were significantly higher in group 1 than group 2 (546.3 ± 172 cc vs. 424.2 ± 185 cc, respectively, p < 0.001). The blood product usage was significantly higher in group 1 than in group 2 (3.3 ± 1.8 units vs.1.7 ± 0.9 units, respectively, p < 0.001). Conclusions: Early CABG operation after ACS is a safely applicable process with acceptable mortality and complication rates.

The inodilator levosimendan: 20 years of experience in various settings of cardiac care

Levosimendan emerged in the 1990s as a first-in-class inotrope and vasodilator that enhances cardiac contractility by sensitizing the contractile response to cardiac troponin C and causes vasodilatation by opening potassium-dependent ATP channels on vascular smooth muscle cells. Since its clinical debut in 2000, it has established itself as a valuable resource in the management of acute decompensated heart failure and is one of very few successful medical innovations of its kind in that field in recent decades. Its pharmacology is notable for delivering inotropy without an increase in myocardial oxygen consumption and for an array of secondary (‘pleiotropic’) effects that include an anti-ischemic effect, pre-conditioning and post-conditioning and cardioprotective effects and anti-oxidative effects. Proceeding from those properties it has been proposed that in addition to its use in various scenarios of low cardiac output levosimendan may be beneficial in other conditions associated with acutely decompensated heart failure, including right ventricular failure, subarachnoid hemorrhage, and cardiogenic shock with multi-organ dysfunction. The potential of levosimendan for kidney protection in situations of the cardio-renal syndrome has been identified. Additional lines of investigation include the use of levosimendan for perioperative hemodynamic support, its administration as repeated intermittent infusions to sustain patients with advanced heart failure and its application in a range of critical care settings. Levosimendan has also provided a template and a starting point for the development of a new generation of cardio-active drugs and is currently being evaluated in advanced clinical trials for the management of pulmonary hypertension in patients with heart failure with preserved ejection fraction.

Levosimendán preoperatorio en cirugía coronaria con disfunción ventricular severa: ¿tiene sentido?

Introduction and objectivesNumerous studies have demonstrated the benefit of levosimendan in patients with chronic and acute heart failure. However, when it comes to its preoperatory use in coronary by-pass surgery in patients with severe ventricular dysfunction, there are some contradictory results. The objective of this study is assessing preconditioning efficiency with levosimendan in surgical myocardial revascularization in patients with severe ventricular dysfunction. MethodsWe design a propensity score-matched cohort study. The study included patients with a LVEF less or equal to 35% who underwent isolated coronary artery by-pass grafting or associated to ischemic/functional mitral surgery from January 2009 to October 2019. They were split into two cohorts whether they received levosimendan preoperatively (Levo) or not (NoLevo); after matching there were 64 patients per cohort. Outcome variables were postoperative morbi-mortality, readmission and follow-up mortality. Statistical analysis: categorical data were compared with a Chi-square or Fisher exact test, and quantitative data with a t-Student or W-Wilcoxon tests. RR/HR were estimated for assessing the association between preoperative use of levosimendan and outcomes. ResultsPreoperative levosimendan use did not decreased in-hospital mortality (RR = 0,86, p = 0.770), and neither do hospital stay, nor postoperative complications. Event-free survival was similar between cohorts in terms of cardiological readmissions, all-cause and cardiological follow-up mortality. ConclusionsOur results do not support the widespread use of levosimendan previously to myocardial revascularization surgery in patients with severe ventricular dysfunction.

Rationale and Design of a Spanish Mulicenter Randomized Controlled Trial of Use of Preoperative Levosimendan to Reduce Low Cardiac Output Syndrome (LCOS) in Low Ejection Fraction (? 35%) Cardiac Surgery Patients Spanish Randomized Clinical Trial on Sindax (Spartans Study)

Background: Low Cardiac Output Syndrome (LCOS) is a complication that appears in approximately 20%of cardiac surgeries with extracorporeal circulation. This is associated with increased mortality, delayed recovery and prolonged hospital stay. The Spanish Randomized Clinical Trial on Sindax (SPARTANS) aims to demonstrate the effectiveness of the preoperative use of levosimendan in reducing LCOS in patients with poor Left Ventricle Ejection Fraction (LVEF) undergoing elective cardiac surgery. Methods: SPARTANS study is a multicenter, randomized triple-blind, placebo-controlled trial. 300 patients with LVEF ≤ 35%, undergoing elective cardiac surgery will be recruited from 9 Spanish hospitals and randomized into two groups: Preoperative administration of levosimendan or placebo for 24 hours. The study drug will be started as a continuous infusion (0.1 μg/kg/ min) at least 8 hours before surgery. The primary endpoint will be 30-day LCOS. It will be evaluated using any of the following criteria: 1) Postoperated cardiac index ≤ 2.0 L/min/m2, 2) Need to implant a intra-aortic balloon pump/left ventricular assist device, 3) Vasoactive inotropic scale (VIS) >5.5. The secondary end-point will be composite event rate at one year including the following events: death from any cause, need for renal replacement therapy or dialysis and LCOS. The sample size is based on the assumption that levosimendan reduces LCOS by 50%. Conclusion: The effectiveness of levosimendan has not yet been reported with a good evidence in cardiac surgery. We will test the hypothesis that levosimendan reduces LCOS in patients with compromised left ventricular function. Trial registration number: NCT04179604 (ClinicalTrials.gov). Rationale and Design of a Spanish Mulicenter Randomized Controlled Trial of Use of Preoperative Levosimendan to Reduce Low Cardiac Output Syndrome (LCOS) in Low Ejection Fraction (≤ 35%) Cardiac Surgery Patients Spanish Randomized Clinical Trial on Sindax (Spartans Study)

Multicenter experiences with levosimendan therapy and its safety in patients with decompensated advanced heart failure.

Advanced heart failure (AdvHF) is associated with high morbidity and mortality. Patients with this clinical condition are potential candidates for heart transplantation or mechanical circulatory support. Initially, however, they are usually supported with inotropic drugs. Recent studies have suggested that levosimendan, independently of hemodynamic improvements, may lead to outcome benefits. To present clinical experiences concerning the indications, effectiveness, tolerance, and safety of levosimendan in the real-life therapy of patients with decompensated AdvHF in 3 cardiac centers in Poland. This is a prospective, observational, three-center study. Forty-nine patients with AdvHF admitted with decompensation were included (88% men, mean age 58 years, 65% ischemic etiology, left ventricular ejection fraction (LVEF) in median 20%) and followed up for an early (3 months) and prolonged period (1 year) after infusion of levosimendan. Patients were analyzed in relation to death. Levosimendan therapy was associated with reduced HF symptoms and signs, New York Heart Association (NYHA) class and level of B-type natriuretic peptide (BNP) at discharge. Five patients died during hospitalization, a further 10 during the three-month follow-up and 3 died during the next nine-month follow-up. During the three-month follow-up, 22 patients were re-hospitalized due to HF and in the next nine-month follow-up 8 were re-hospitalized. A multivariate analysis indicated the QRS duration at discharge (hazard ratio (HR) = 1.02; 95% confidence interval (95% CI) = 1.003-1.03; p = 0.018), high-sensitivity C-reactive protein (hsCRP) (HR = 1.01; 95% CI = 1.004-1.02; p = 0.002), and simultaneous dobutamine infusion (HR = 6.54; 95% CI = 1.4-30.5; p = 0.017) were independent risk factors for death in the one-year follow-up. There were no side effects leading to the interruption of the levosimendan infusion. The use of levosimendan was safe and associated with clinical improvement and reduction in BNP level in AdvHF patients hospitalized due to HF decompensation, although the mortality and re-hospitalization rate during the one-year follow-up remains high.

Levosimendan and Global Longitudinal Strain Assessment in Sepsis (GLASSES 1): a study protocol for an observational study

IntroductionCardiogenic shock is a condition of low cardiac output that represents the end stage of a progressive deterioration of cardiac function. The main cause is ischaemic heart disease, but there...

Levosimendan in the treatment of patients with acute cardiac conditions: an expert opinion of the Association of Intensive Cardiac Care of the Polish Cardiac Society.

Levosimendan is a new inodilator which involves 3 main mechanisms: increases the calcium sensitivity of cardiomyocytes, acts as a vasodilator due to the opening of potassium channels, and has a cardioprotective effect. Levosimendan is mainly used in the treatment of acute decompensated heart failure (class IIb recommendation according to the European Society of Cardiology guidelines). However, numerous clinical trials indicate the validity of repeated infusions of levosimendan in patients with stable heart failure as a bridge therapy to heart transplantation, and in patients with accompanying right ventricular heart failure and pulmonary hypertension. Due to the complex mechanism of action, including the cardioprotective and anti- -aggregating effect, the use of levosimendan may be particularly beneficial in acute coronary syndromes, preventing the occurrence of acute heart failure. There are data indicating that levosimendan administered prior to cardiac surgery may improve outcomes in patients with severely impaired left ventricular function. The multidirectional mechanism of action also affects other organs and systems. The positive effect of levosimendan in the treatment of cardiorenal and cardiohepatic syndromes has been shown. It has a safe and predictable profile of action, does not induce tolerance, and shows no adverse effects affecting patients survival or prognosis. However, with inconclusive results of previous studies, there is aneed for awell-designed multicenter randomized placebo-‑controlled study, including an adequately large group of outpatients with chronic advanced systolic heart failure.

Levosimendan as a bridge to heart transplant in a 16-year-old patient with univentricular heart

We report the successful use of levosimendan in the treatment of heart failure in a patient with the univentricular heart. The presented case was atypical because our patient had systemic right ventricle. To our knowledge, it is the first reported such case with intermittent levosimendan administration as an effective treatment and bridge to successful heart transplant in a patient with functionally univentricular heart.

Can levosimendan reduce ECMO weaning failure in cardiogenic shock?: a cohort study with propensity score analysis

BackgroundVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used over the last decade in patients with refractory cardiogenic shock. ECMO weaning can, however, be challenging and lead to circulatory failure and death. Recent data suggest a potential benefit of levosimendan for ECMO weaning. We sought to further investigate whether the use of levosimendan could decrease the rate of ECMO weaning failure in adult patients with refractory cardiogenic shock.MethodsWe performed an observational single-center cohort study. All patients undergoing VA-ECMO from January 2012 to December 2018 were eligible and divided into two groups: group levosimendan and group control (without levosimendan). The primary endpoint was VA-ECMO weaning failure defined as death during VA-ECMO treatment or within 24 h after VA-ECMO removal. Secondary outcomes were mortality at day 28 and at 6 months. The two groups were compared after propensity score matching. P < 0.05 was considered statistically significant.ResultsTwo hundred patients were analyzed (levosimendan group: n = 53 and control group: n = 147). No significant difference was found between groups on baseline characteristics except for ECMO duration, which was longer in the levosimendan group (10.6 ± 4.8 vs. 6.5 ± 4.7 days, p < 0.001). Levosimendan administration started 6.6 ± 5.4 days on average following ECMO implantation. After matching of 48 levosimendan patients to 78 control patients, the duration of ECMO was similar in both groups. The rate of weaning failure was 29.1% and 35.4% in levosimendan and control groups, respectively (OR: 0.69, 95%CI: 0.25–1.88). No significant difference was found between groups for all secondary outcomes.ConclusionLevosimendan did not improve the rate of successful VA-ECMO weaning in patients with refractory cardiogenic shock.Trial registrationClinicalTrials.gov, NCT04323709.

Impact of the perioperative inotropic support in grown-up congenital heart patients undergoing cardiac surgery: a propensity score adjusted analysis

BackgroundGrown-up congenital heart (GUCH) patients represent a growing population with a high morbidity risk when undergoing reparative surgery. A main preoperative feature is right ventricular failure, which represents a risk factor for postoperative low cardiac output syndrome. Levosimendan has a potentially beneficial effect. This retrospective study included consecutive GUCH patients with surgeries in a tertiary cardiothoracic centre between 01-01-2013 and 01-10-2017, to test the hypothesis that the postoperative use of levosimendan might be associated with shorter time of mechanical ventilation, when compared with the use of milrinone. To adjust for bias related to the probability of treatment assignment, it uses the inverse propensity score weighting methodology.ResultsOverall 363 patients had GUCH surgeries during the study period, their mean age was 31.39 ± 15.31 years, 87 patients were eligible for analysis in the Levosimendan group and 117 in the Milrinone group. The propensity score used pre- and intraoperative variables and resulted in a good balance between covariates. The Levosimendan group included patients with higher preoperative risk scores, a higher prevalence of left and right ventricular failure, who required more often the addition of epinephrine, renal replacement therapy, prolonged mechanical ventilation and intensive care stay. However, after propensity score weighting, patients in the Levosimendan group had shorter durations of mechanical ventilation (average treatment effect − 37.59 h IQR [− 138.85 to − 19.13], p = 0.01) and intensive care stay (average treatment effect − 3.11 days IQR [− 10.03 to − 1.48], p = 0.009). The number of days of additional epinephrine support was shorter and the vasoactive inotropic scores lower.ConclusionWe report a beneficial effect in terms of duration of mechanical ventilation and intensive care stay, and on inotropic requirements of the use of levosimendan following GUCH surgeries. The use of levosimendan in this setting requires validation at a larger scale.

Effects of levosimendan on weaning and survival in adult cardiogenic shock patients with veno-arterial extracorporeal membrane oxygenation: systematic review and meta-analysis.

Veno-arterial extracorporeal membrane oxygenation may be used to support patients with refractory cardiogenic shock. Many patients can be successfully weaned, the ability of some medications to facilitate weaning from veno-arterial extracorporeal membrane oxygenation were reported. To date, there are limited studies investigating the impact of levosimendan on veno-arterial extracorporeal membrane oxygenation weaning. The objective of this systematic review and meta-analysis was to assess the effects of levosimendan on successful weaning from veno-arterial extracorporeal membrane oxygenation and survival in adult patients with cardiogenic shock. We performed a systematic review and meta-analysis (PubMed, the Cochrane Library, and the International Clinical Trials Registry Platform published from the year 2000 onwards) investigating whether levosimendan offers advantages compared to standard therapy or placebo, in cardiogenic shock adult patients treated with veno-arterial extracorporeal membrane oxygenation. The primary outcome was veno-arterial extracorporeal membrane oxygenation successful weaning, whereas secondary outcome was all-cause mortality at the longest follow-up available. We pooled risk ratio and 95% confidence interval using fixed and random effects models according to the heterogeneity. A total of five non-randomized clinical trials comprising 557 patients were included, 299 patients for levosimendan and 258 patients for control groups. The pooled prevalence of veno-arterial extracorporeal membrane oxygenation successful weaning was 61.4% (95% confidence interval 39.8-82.9%), and all-cause mortality was 36% (95% confidence interval 29.6-48.8%). There was a significant increase in veno-arterial extracorporeal membrane oxygenation successful weaning with levosimendan compared to the controls (risk ratio = 1.42 (95% confidence interval 1.12-1.8), p for effect = 0.004, I2 = 71%). A decrease risk of all-cause mortality in the levosimendan group was also observed, risk ratio = 0.62 (95% confidence interval 0.44-0.88), p for effect = 0.007, I2 = 36%. The use of levosimendan on adult patients with cardiogenic shock may facilitate the veno-arterial extracorporeal membrane oxygenation weaning and reduce all-cause mortality. Few articles of this topic are available, and prospective, randomized multi-center trials are warranted to conclude decisively on the benefits of levosimendan in this setting.

Preconditioning with levosimendan reduces postoperative low cardiac output in moderate-severe systolic dysfunction patients who will undergo elective coronary artery bypass graft surgery: a cost-effective strategy

BackgroundPatients with moderate-severe systolic dysfunction undergoing coronary artery bypass graft have a higher incidence of postoperative low cardiac output. Preconditioning with levosimendan may be a useful strategy to prevent this complication. In this context, design cost-effective strategies like preconditioning with levosimendan may become necessary.MethodsIn a sequential assignment of patients with Left Ventricle Ejection Fraction less than 40%, two strategies were compared in terms of cost-effectiveness: standard care (n = 41) versus preconditioning with Levosimendan (n = 13). The adverse effects studied included: postoperative new-onset atrial fibrillation, low cardiac output, renal failure and prolonged mechanical ventilation. The costs were evaluated using deterministic and probabilistic sensitivity analysis, and Monte Carlo simulations were performed.ResultsPreconditioning with levosimendan in moderate to severe systolic dysfunction (Left Ventricle Ejection Fraction < 40%), was associated with a lower incidence of postoperative low cardiac output in elective coronary artery bypass graft surgery 2(15.4%) vs 25(61%) (P < 0.01) and lesser intensive care unit length of stay 2(1–4) vs 4(3–6) days (P = 0.03). Average cost on levosimendan group was 14,792€ while the average cost per patient without levosimendan was 17,007€. Patients with no complications represented 53.8% of the total in the levosimendan arm, as compared to 31.7% in the non-levosimendan arm. In all Montecarlo simulations for sensitivity analysis, use of levosimendan was less expensive and more effective.ConclusionsPreconditioning with levosimendan, is a cost-effective strategy preventing postoperative low cardiac output in patients with moderate-severe left ventricular systolic dysfunction undergoing elective coronary artery bypass graft surgery.

Clinical study of Perioperative Use of Levosimendan in Patients Undergoing Heart Valve Replacement

Objective To investigate the clinical effect of levosimendan in perioperative aortic and/or mitral valve replacement. Methods Patients undergoing open heart aortic and/or mitral valve replacement in our hospital from January 2018 to December 2019 were enrolled. 45 patients in the control group received routine perioperative treatment based on dopamine, while 45 patients in the research group received continuous perioperative administration of levosimendan injection for 24h on the basis of routine treatment. The left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd) and left ventricular end-systolic diameter (LVDs) were evaluated by color doppler echocardiography before and one week after surgery. Postoperative mechanical ventilation weaning time, length of ICU stays, number of vasoactive drugs used and withdrawal time; indexes of liver and kidney function before and on the day after surgery to 10 days after surgery; use of in vitro support techniques such as aortic balloon pulsation (IABP), continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) within 5 days of perioperative period. Results The improvement of LVDs and LVEF in the study group using levosimendan one week after the operation was significantly better than that in the control group (P value was 0.013 and 0.001, respectively), and fewer kinds of vasoactive drugs were needed (P<0.001), and the risk of postoperative AKI in the study group was significantly lower than that in the control group ( P=0.047 ). Conclusion The perioperative use of levosimendan can effectively promote the recovery of cardiac systolic function and reduce the risk of postoperative AKI.

Influencing factors of postoperative acute kidney injury in patients undergoing cardiac surgery

Objective: To analyze the influencing factors of acute kidney injury (AKI) in patients after cardiac surgery using levosimendan or dobutamine, and explore the effect of positive inotropic drugs on AKI. Methods: The clinical data of 417 patients undergoing cardiac surgery from January to June 2018 in Beijing Anzhen Hospital and treated with levosimendan or dobutamine during perioperative period were retrospectively reviewed and collected. Patients were divided into AKI group and non-AKI group according to whether AKI occurred. Univariate logistic regression analysis was used to analyze the factors related to the occurrence of AKI. The statistically significant factors (P<0.05) were further included in the multivariate logistic regression analysis. Results: Totally, 417 patients were enrolled in the study, with a mean age of (58.2±10.4) years old and a male rate of 65.0% (n=271), and the AKI incidence rate was 25.2% (105/417). Univariate logistic regression analysis showed that male, chronic kidney disease, high serum creatinine level in preoperative period, aortic obstruction time ≥ 120 minutes and extracorporeal circulation time ≥ 120 minutes were risk factors for AKI (all P<0.05). Vasodilator and levosimendan treatment during perioperative period were protective factors (P<0.05). Multivariate logistic regression analysis showed that chronic kidney disease (OR=17.291, 95%CI: 4.335-68.960, P<0.001) and high serum creatinine level (OR=1.097, 95%CI: 1.074-1.121, P<0.001) in preoperative period were independent risk factors for AKI. Perioperative application of levosimendan (OR=0.533, 95%CI: 0.288-0.984, P=0.044) was an independent protective factor. Conclusions: Risk factors for AKI after cardiac surgery include chronic kidney disease and high serum creatinine level in preoperative period. The use of levosimendan during preoperative period has the potential effect to protect against AKI.

Levosmindan: A new step up in Management in Neonatal Cardiogenic shock

Abstract We report the use of Levosimendan, calcium sensitizer, inodilator in a neonate with post-operative refractory cardiogenic shock. Currently, no data are available on the use of levosimendan in newborns outside the cardiosurgical setting. A 38-week neonate -with isolated exomphalos major-presented post-operatively with pulmonary hypertension, refractory cardiogenic shock (inspite of receiving, a bolus of 10ml/kg, Dopamine and Dobutamine 15µg/kg/min, Adrenaline up to 1mg/Kg/min, Noradrenaline 0.5mg/Kg/min, Terlipressin 20µg/Kg/hour, Milrinone 25µg/Kg/min) and arrhythmia (supraventricular tachycardia). Levosimendan was introduced as an intravenous infusion with an initial rate of 0.1 up to 0.2µg/Kg/min in addition to Noradrenaline 1µg/Kg/min, Dopamine 15µg/Kg/min and Furosemide infusion 0.1mg/Kg/hour. The patient improved evidenced by normalization of vital signs and restoration of perfusion with better cardiac functions by echocardiography. Conclusion: Levosimendan has positive inotropic, lusitropic and vasodilating effects for the treatment of heart failure yet further studies in neonates are still required.

Levosimendan to facilitate weaning from cardiorespiratory support in critically ill patients: current evidence and future directions.

Appropriate weaning is of crucial importance for critically ill patients requiring respiratory support. However, a remarkable proportion of them are difficult to wean. Levosimendan is a positive inotropic agent characterized by vasodilatory properties, which is used for the treatment of acute decompensated heart failure or in patients needing inotropic treatment, including cardiogenic shock, septic shock, pulmonary hypertension and right ventricular dysfunction, needed for hemodynamic support in patients with diuretic resistance, and weaning either from ventilator or from extracorporeal membrane oxygenation. This position paper will discuss the use of levosimendan in facilitating weaning from cardiorespiratory support in critically ill patients, according to available evidence and the personal experience of a group of Italian Experts.

Effects of levosimendan on ventriculo-arterial coupling and cardiac efficiency in paediatric patients with single-ventricle physiology after surgical palliation: retrospective study.

The use of levosimendan for paediatric patients with low cardiac output after congenital heart surgery has been recently described. We sought to evaluate ventriculo-arterial coupling (VAC) and other ventricular energetic parameters before and after 72 h from levosimendan start in infants with single-ventricle physiology and cardiac failure after palliation with Norwood or hybrid procedures. In this single-centre retrospective study, 9 consecutive patients affected by hypoplastic left heart syndrome-like anatomy were retrospectively analysed. Systolic elastance, diastolic elastance, arterial elastance, VAC and cardiac mechanical efficiency were calculated by measuring, through 2-dimensional echocardiography, end-systolic volume and end-diastolic volume and by recording mean arterial pressure and central venous pressure. The median (range) weight and age were 2.8 (2.3-6) kg and 16.5 (6-116) days, respectively. After 72 h from levosimendan start, end-systolic volume significantly decreased (-1 ml, -3.2 to -0.1, P = 0.007), whereas mean arterial pressure and end-diastolic volume remained stable. Heart rate showed a significant decrease (-28 beats/min, -41 to 22, P = 0.008). Systolic elastance (2.9 mmHg/ml, 0.4-5.4, P = 0.008), arterial elastance (-5.9, -24 to -0.5, P = 0.038), VAC (-0.86, -1.5 to -0.16, P = 0.009) and cardiac mechanical efficiency (0.18, 0.03-0.22, P = 0.008) differences also showed significant modifications. In a small case series of patients with single-ventricle physiology, levosimendan showed to improve contractility and optimize VAC, with a reduction of heart rate. Monitoring of VAC and ventricular energetics can be an interesting aspect to improve the management of heart failure in infants with univentricular anatomy.

A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury.

Ischemia-reperfusion injury (IRI) is cellular damage that emerges from re-oxygenation of a hypoxic organ. In the present study, we aimed to examine the effects of a combination of levosimendan, an inotropic agent, and N-Acetylcysteine, the precursor of antioxidants and glutathione, in an experimental liver IRI model. In this study, 38 rats were randomly divided into five groups. Before the ischemia, study arms were given physiological saline solution, N-Acetylcysteine (NAS), levosimendan or a combination of NAS+levosimendan in a predetermined amount and duration, and the infusion was continued until the end of this study. The hepatic pedicle was occluded using an atraumatic vein clamp, and 60 minutes of ischemia was achieved. The clamp was then opened and 60 minutes of reperfusion was ensured. Liver tissue samples were obtained after sacrifice, and tissue malondialdehyde (MDA) and myeloperoxidase (MPO) levels were determined. Serum Tumor Necrosis Factor (TNF)-α, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and MPO levels of blood samples were also measured. Among the histopathological changes in the liver tissue after IRI, differences between groups were statistically significant in the injury scoring system based on congestion, vacuolization and necrosis levels. Histopathological injury score, plasma MPO, AST, ALT, tissue MPO and tissue MDA values were statistically significantly lower in the treatment groups, prominently in the levosimendan and NAS combination group concerning liver histopathological damage. The use of a levosimendan plus NAS combination in liver IRI markedly suppressed inflammation and oxidative stress and significantly reduced liver ischemia-reperfusion injury and can be recommended for decreasing IRI instead of single agent use of levosimendan or NAS.

134 Levosimendan Use in Patients With Severe Heart Failure: A Single-Centre Descriptive Study

The role and indications for levosimendan use in patients with heart failure are unclear. To investigate the context and clinical course of patients with severe heart failure who receive levosimendan. This study is a single-centre, retrospective case review of patients who received levosimendan between December 2018 and January 2020. Outcomes included patient disposition, re-hospitalisations, and adverse events. Twenty-three patients were included. Seven patients had ischaemic cardiomyopathy. Left ventricular ejection fractions ranged from 8% - 30%. Sixteen patients received levosimendan to facilitate weaning off continuous inotropes. Eleven of these did so successfully and were discharged, two required a left ventricular assist device (LVAD) prior to discharge, and three died in hospital (two were for palliative treatment only). Four patients received levosimendan for poor diuresis in the setting of cardiorenal syndrome, of whom three were discharged without requiring dialysis and one died in hospital. Three patients received levosimendan as first-line therapy for cardiogenic shock and all were discharged. Amongst the 19 discharged, six patients were discharged with a plan for outpatient assessment of heart transplant candidacy. Of these, two patients subsequently received transplants and one died at home while on the waitlist. Seven of the 19 patients that were discharged were re-admitted with cardiac decompensation, two of which required LVAD implantation. We have successfully used levosimendan in patients with heart failure to achieve the following goals: 1) weaning of continuous inotropes in patients with cardiogenic shock to facilitate discharge from hospital and 2) bridging patients to further advanced heart failure therapies.

Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial

BackgroundThe administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts.MethodsThis was a single-center, double-blind, randomized, placebo-controlled trial. Patients ≤ 48 months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48 h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study.ResultsA total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19–1.13; p = 0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14–3.69, p = 0.693), duration of mechanical ventilation (median, 47.5 h and 39.5 h, respectively; p = 0.532), ICU stay (median, 114.5 h and 118 h, respectively; p = 0.442), and hospital stay (median, 20 days and 20 days, respectively; p = 0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS.ConclusionsProphylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo.Trial registrationName of the registry: Safety evaluation and therapeutic effect of levosimendan on the low cardiac output syndrome in patients after cardiopulmonary bypass. Trial registration number: ChiCTR1800016594. Date of registration: 11 June 2018. URL of trial registry record: http://www.chictr.org.cn/index.aspx