Levosimendan Group Research Articles

After an acute coronary syndrome: levosimendan or dobutamine? this is our impression

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Inotropic support is frequently needed after acute coronary syndromes(ACS) at coronary care units(CCU). Despite it has being long time since approval of levosimendan(LV) as inotropic support to cardiogenic shock, dobutamine(DB) still being the basis of this treatment. We think levosimendan is a secure and effective alternative. Purpose To analyse the use of levosimendan and dobutamine done in our ACS patients to determine if we have followed some clear criteria of selection, and try to draw a defined pattern for future use. Method Retrospective, analytic, observational study of all ACS admitted to our CCU between 08/2011- 02/2022. We confront patients treated with dobutamine versus levosimendan. X2, U-Mann Whitney and T-Student were used when necessary. Statistical significance: p-value<0.05. Result 2881patients were admitted with ACS, 6.49%of them(n: 187) needed ionotropic support. Out of these, 60.96%(n: 114) were supported with dobutamine, 28.88%(n: 54) with levosimedan and 10.16%(n: 19)received in some time both drugs, so were excluded from the analysis. Mean age: 68.43±11.48years old. 66.66%(n: 112) men. 54.76%(n: 92)with persistent ST-segment elevation. No difference was found between groups, neither in past medical history, including cardiovascular risk factors, history of arrhythmias(11.3% of patients), previous use of betablockers(30.4%), antiarrhythmic drugs(0.6%) or having pacemaker(1.2%). 114 patients(67.86%)needed norepinephrine(70.17%with DB and 62.96% LV, p:0.35); 29(17.26%) were supported with intra-aortic balloon pump(20.18% in DB group and 11.11% in LV group, p:0.134), without differences by drug. 62 patients(36.9%) presented atrial fibrillation(33.33% in DB and 44.44% in LV, p:0.166), 58(34.52%)ventricular arrhythmias[sustained ventricular tachycardia/ventricular fibrillation](33.33% in DB and 37.04% in LV, p:0.638). In-hospital mortality of these patients was 29.17%(n:49), 29.82% in DB and 27.77% in LV, p:0.785. In multivariate analysis adjusted by clinic and epidemiologic factors, only cardiogenic shock resulted an independent predictor of in-hospital death. Pattern of use we use DB in those patients with worst Killip-kimball(KK) state(73.54%in DB group with KK-IV vs53.70%in LV´s) and LV in those in intermediate states of instability(38.88%LV in KK-II/III vs 8.84%DB in KK-II/III),p<0.001. We chose DB in those who became unstable in CCU and LV in those who became unstable in hospitalization room, p:0.049. Finally, we noted a significant change in trend of use during the period of study, falling use of DB in favour of LV(p<0.001). Conclusion In our experience, dobutamine has been the most frequent ionotropic drug used in last 11 years after an acute coronary syndrome. Nevertheless, a substitution by levosimendan trend is evolving. We did not detect differences in complications or prognosis dependent on the inotropic drug used, but the use of dobutamine were predominant in those patients with more severe situation.

Comparison between levosimendan versus beta agonists in preservation of renal function in cardiac surgery patients with low cardiac output syndrome

ABSTRACT Background Post cardiac surgery acute kidney injury (AKI) secondary to postoperative low cardiac output syndrome (LCOS), is a serious complication. Positive inotropic agents are the main line of treatment for LCOS with different degrees of improvement of cardiac function & nephroprotective efficacy Levosimendan is a calcium sensitizer in cardiac muscles, which has a comparable positive inotropic and nephroprotective effects to that of classic beta2 agonists. Objective To evaluate the possible nephroprotective effect of levosimendan as compared to beta agonists in cardiac surgery patients with LCOS. Patients and Methods It is a prospective, randomized and comparative study conducted at Ain Shams University Hospitals over the period from December 2020 to May 2021. A total of 60 patients with post cardiac surgery low cardiac output syndrome were divided into two groups of 30 patients each. Group A (control) received beta-agonists (dobutamine or adrenaline) and Group B (study) received levosimendan. The incidence of AKI at the diagnosis of LCOS & its progression to renal failure in both groups were assessed. Results The incidence of AKI at diagnosis of LCOS postoperative was 30% (n = 9) in each group; 44% of them in the control group (n = 4) developed renal failure at discharge from ICU and none of the study group patients developed renal failure at discharge. At the time of discharge from ICU, the incidence of renal failure in beta-agonist group was 13.3%, while the incidence in the levosimendan group was 0% with statistically significant P value of 0.038. Conclusion In comparison to beta-agonists, Levosimendan may have a better nephroprotective effect that plays a role in decreasing the incidence of kidney failure in patients with post cardiac surgery LCOS. A larger randomized, controlled trials are recommended to prove such a beneficial nephroprotective effect and its exact mechanism.

The impact of levosimendan on survival and weaning from ECMO after extracorporeal cardiopulmonary resuscitation.

Extracorporeal cardiopulmonary resuscitation (eCPR) is increasingly used due to its beneficial outcomes and results compared to conventional CPR. After cardiac arrest, the overall ejection fraction is severely impaired; thus, weaning from ECMO is often prolonged or impossible. We hypothesized that early application of levosimendan in these patients facilitates ECMO weaning and survival. From 2016 until 2020, patients who underwent eCPR after cardiac arrest at our institution were analyzed retrospectively and divided into two groups: patients who received levosimendan during ICU stay (n = 24) and those who did not receive levosimendan (n = 84) and analyzed for outcome parameters. Furthermore, we used propensity-score matching and multinomial regression analysis to show the effect of levosimendan on outcome parameters. Overall, in-hospital mortality was significantly lower in the group which received levosimendan (28% vs. 88%, p ≤ 0.01), and ECMO weaning was more feasible in patients who received levosimendan (88% vs. 20%, p ≤ 0.01). CPR duration until ECMO cannulation was significantly shorter in the levosimendan group (44 + 26 vs. 65 + 28, p = 0.002); interestingly, the rate of mechanical chest compressions before ECMO cannulation was lower in the levosimendan group (50% vs. 69%, p = 0.005). In patients after cardiac arrest treated with eCPR, levosimendan seems to contribute to higher success rates of ECMO weaning, potentially due to a short to mid-term increase in inotropy. Also, the survival after levosimendan application was higher than patients who did not receive levosimendan.

Levosimendan or Milrinone for Ventricular Septal Defect Repair With Pulmonary Arterial Hypertension

Both milrinone and levosimendan have been used in patients undergoing surgical closure of ventricular septal defects (VSD) with pulmonary artery hypertension (PAH); however, the evidence base for their use is limited. In the present study, the authors sought to compare the role of levosimendan and milrinone in the prevention of low-cardiac-output syndrome in the early postoperative period. A prospective, randomized, controlled trial. At a tertiary-care center. Children between 1 month and 12 years presenting with VSD and PAH between 2018 and 2020. A total of 132 patients were randomized into the following 2 groups: Group L (levosimendan group) and Group M (milrinone group). In addition to conventional hemodynamic parameters, the authors also included a myocardial performance index assessment to compare the groups. The levosimendan group had significantly lower mean arterial pressure while coming off cardiopulmonary bypass, after shifting to intensive therapy unit, as well as at 3 and 6 hours postoperatively. The duration of ventilation (29.6 ± 13.9 hours v 23.2 ± 13.3 hours; p=0.012), as well as postoperative intensive care unit stay, were significantly prolonged in the levosimendan group (5.48 ± 1.2 v 4.7 ± 1.3 days, p=0.003). There were 2 (1.6%) in-hospital deaths in the entire cohort, 1 in each arm. There was no difference in the myocardial performance index of the left or right ventricle. In patients undergoing surgical repair for VSD with PAH, levosimendan does not confer any additional benefit compared to milrinone. Both milrinone and levosimendan appear to be safe in this cohort.

Levosimendan as adjuvant therapy for cardiogenic shock patients with temporary ventricular assist device

Background: Temporary ventricular-assisted device (VAD) provides timely organ perfusion in patients with cardiogenic shock and serves as a bridge to heart transplant. Intravenous levosimendan could provide pharmacologic inotropic support. Aim: We aimed to investigate the adjuvant efficacy of levosimendan in patients with temporary VAD, especially for VAD weaning. Methods: We retrospectively reviewed the medical records of patients receiving temporary VAD for cardiogenic shock between January 2017 and May 2019 in a medical center in Taiwan. Patients were divided into the levosimendan (n = 9, administered levosimendan immediately after VAD), and control groups (n = 20, no levosimendan administered). The biochemistry of systemic perfusion was compared at 1 and 3 days after VAD. After 2 months, the cardiac function of the patients with successful VAD weaning was evaluated by echocardiography. At 6 months follow-up, survival outcome and Kaplan–Meier survival curves were presented. Results: In total, 29 patients receiving temporary VAD for cardiogenic shock were enrolled, including 9 patients treated with levosimendan infusion. In the levosimendan group, both mean arterial pressure and lactate level decreased significantly (P = 0.037 and 0.023, respectively), and the ratio of arterial oxygen partial pressure to fractional inspired oxygen improved significantly (P = 0.048). No difference in inotropes tapering, consciousness, systemic perfusion biochemistry, and cardiac enzymes. Echocardiography showed significantly improved systolic function and pulmonary artery pressure 2 months later (P = 0.043 and 0.046, respectively) in patients with successful weaning. The levosimendan group had a better weaning rate (P = 0.013) and lower mortality rate (P = 0.571) at 6-month follow-up. Conclusion: The levosimendan group showed a better weaning rate and lower mortality rate.

Effect of Levosimendan on the Prognosis of Cardiac Surgery in Patients with Cardiac Insufficiency

Objective: To retrospectively analyze the effect of levosimendan on the survival and prognosis of cardiac surgery patients with LVEF<40%. Methods: The clinical data of 224 patients with preoperative LVEF<40% were retrospectively analyzed. According to different treatment schemes, the patients were divided into levosimendan group (n=60) and non-levosimendan group (n=164). The control group was treated with routine treatment, and the observation group was treated with levosimendan on the basis of routine treatment. Then a multivariate logistic regression model with a propensity score analysis was used to limit biases and finally the data of 40 patients in each group were selected for analysis. Results: Hemodynamic data showed that the cardiac index, LVEF and PAOP of patients in levosimendan group were significantly improved. The concentration of serum lactic acid in the levosimendan group was lower than that in the control group (P<0.05). At the same time, postoperative ICU and hospital stay were significantly reduced in levosimendan group (P<0.05), Logistics regression analysis showed that levosimendan was the only protective factor for Low cardiac output syndrome (LCOS) (HR=4.33; 95% confidence interval: 1.27-14.78; P=0.019). Conclusion: Levosimendan can better improve hemodynamics and reduce postoperative ICU time and hospital stay. The use of it tends to decrease the incidence of LCOS significantly.

Efficacy of Levosimendan in the Treatment of Patients With Severe Septic Cardiomyopathy

This study was designed to compare the effects of levosimendan and dobutamine on hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤35%). A prospective, single-blind, randomized controlled study. In Baoding, China. Thirty patients with severe septic cardiomyopathy treated in the authors' hospital's Department of Critical Medicine from September 2018 to September 2021 were enrolled in this study. These patients were divided randomly into the levosimendan group and dobutamine group. The LVEF, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index, heart rate, norepinephrine dose, and lactate at the time of enrollment and the 24th hour were compared, along with myocardial injury markers on the third day, C-reactive protein, mechanical ventilation time, length of intensive care unit (ICU) stay, cost, and 28-day mortality. The primary outcome was28-day mortality. At the 24th hour after treatment, CI, LVEF, SVI, and fluid volume were found to be higher in the levosimendan group than in the dobutamine group, whereas the dose of norepinephrine was lower in the former rather than the latter group. On the third day of treatment, cardiac troponin I in the levosimendan group was lower than that in the dobutamine group. Although the differences in 28-day mortality, ICU stay, and ICU treatment cost between the groups were not statistically significant, the ventilator application time of the levosimendan group was significantly shorter than that of the dobutamine group. Compared with dobutamine, levosimendan was more effective at improving cardiac function, reducing myocardial injury, and reducing mechanical ventilation time in patients with severe septic cardiomyopathy.

The effects of levosimendan in patients undergoing transcatheter aortic valve replacement- a retrospective analysis.

Background: Aortic stenosis (AS) increases left ventricular afterload, leading to cardiac damage and heart failure (HF). Transcatheter aortic valve replacement (TAVR) is an effective therapy for AS. No inotropic agents including levosimendan have been evaluated in patients undergoing TAVR. Methods: A total of 285 patients underwent TAVR between 2014 and 2019; 210 were included in the matched analysis and 105 received 0.1μg/kg body weight/min levosimendan immediately after the prosthesis had been successfully implanted. Medical history, laboratory tests, and echocardiography results were analyzed. Endpoints including 2-year all-cause mortality, stroke, or HF-related hospitalization, and a combination of the above were analyzed by Cox proportional hazard models. Results: The levosimendan group had no difference in 2-year mortality compared with the control group (hazard ratio [HR]: 0.603, 95% confidence interval [CI]: 0.197-1.844; p = 0.375). However, levosimendan reduced stroke or HF-related hospitalization (HR: 0.346; 95% CI: 0.135-0.884; p = 0.027) and the combined endpoint (HR: 0.459, 95% CI: 0.215-0.980; p = 0.044). After adjusting for multiple variants, levosimendan still reduced stroke or HF-related hospitalization (HR: 0.346, 95% CI: 0.134-0.944; p = 0.038). Conclusion: Prophylactic levosimendan administration immediately after valve implantation in patients undergoing TAVR can reduce stroke or HF-related hospitalization but does not lower all-cause mortality.

The effect of post-reperfusion levosimendan in an experimental intestinal ischemia–reperfusion model

BackgroundLevosimendan has been reported to have a positive effect on ischemia–reperfusion injury. Herein, we aimed to evaluate the effects of levosimendan applied after reperfusion in an experimental intestinal injury-reperfusion (IR) model.MethodsTwenty-one Wistar-albino male rats were separated into three groups: Sham group (n = 7): solely superior mesenteric artery (SMA) was dissected after laparotomy; intestinal ischemia–reperfusion group (IIR, n = 7): SMA was clamped for 60 min and unclamped for 120 min to cause ischemia–reperfusion; IIR + levosimendan group (IIR + L, n = 7): levosimendan was administered in ischemia–reperfusion model. The mean arterial pressures (MAP) were measured in all groups. MAP measurements were performed at the end of stabilization, at the 15th, 30th, and 60th minute of ischemia; at the 15th, 30th, 60th, and 120th minute of reperfusion; and at the end of levosimendan bolus application and when levosimendan infusion concluded. Reperfusion injury was evaluated with tissue malondialdehyde (MDA) and by Chiu score.ResultsMAP at 15 min, 30 min, and 60 min of reperfusion was lower in IIR and IIR + L groups compared with basal inter-group measurements. Decline in MAP at 30 min after reperfusion was statistically significant in IIR and IIR + L groups when compared with the sham group. There was no significant difference between MDA levels in the groups. Chiu score was significantly lower in the sham group when compared to IIR and IIR + L groups and higher in IIR when compared to the IIR + L group.ConclusionLevosimendan leads to a decrease in intestinal damage although it did not affect lipid peroxidation and MAP when administered after reperfusion in an experimental intestinal IR model.

Endothelial Dysfunction in Patients with Advanced Heart Failure Treated with Levosimendan Periodic Infusion Compared with Optimal Medical Therapy: A Pilot Study.

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.

Association of Repetitive Dosing of Levosimendan with Reduction of NYHA Class and NT-proBNP Levels in Decompensated Heart Failure: A Retrospective Cohort Study.

BackgroundThere is evidence that repetitive administration of levosimendan can improve outcome in chronic heart failure patients.ObjectiveThe aim of this retrospective study was to investigate the effect of therapy with levosimendan (LEV) additional to standard medical care in patients with symptomatic heart failure (HFrEF = heart failure with reduced ejection fraction) on NYHA class, NT-proBNP values, ejection fraction (EF) and body weight.Patients and Methods178 participating patients (125 male, 53 female; mean age of 73 ± 13 years) were grouped according to whether LEV was given once (group 1) or repetitively (group 2). In group 2 data were analysed for first treatment with LEV (group 2a) and for the following repetitive LEV treatments (group 2b). The differentiation was required to see if there were different results for the particular groups.ResultsRepetitive dosing was given between two and 11 times, leading to 47 repetitive applications of LEV and a total of 225 (178 once + 47 repetitive) applications. The mean time between the repetitive dosing was 133 days or 4.3 months. LEV in addition to standard medical treatment was associated with reduction of NT-proBNP levels from 9138 to 7051 pg/mL (p < 0.05). The corresponding values in group 2a and group 2b were 8790–4717 pg/mL (p < 0.05) as well as 13,681–7581 pg/mL (p < 0.05). The ejection fraction measured by echocardiography improved from 30 to 38% in group 1, from 31 to 45% in group 2a and from 30 to 35% in group 2b (p < 0.05). Addition of LEV was associated with significant reduction of NYHA class and bodyweight in all groups. No adverse side effects (e.g., rhythm disorder, hypotension, electrolyte disorder) were seen.ConclusionLEV may be useful as an additive to standard care of treatment for patients with acute de novo decompensation due to acute heart failure as well as to prevent further deterioration in patients with chronic heart failure disease at high risk for hospitalisation. Intraindividual changes in NT-proBNP levels may be useful in decision-making about the need for additional treatment options in patients with worsening heart failure.

Early Levosimendan Administration Improved Weaning Success Rate in Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock.

BackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used in patients with refractory cardiogenic shock (CS) or out-of-hospital cardiac arrest. It is difficult to perform VA-ECMO weaning, which may cause circulatory failure and death. Levosimendan is an effective inotropic agent used to maintain cardiac output, has a long-lasting effect, and may have the potential benefit for VA-ECMO weaning. The study aimed to explore the relationship between the early use of levosimendan and the rate of VA-ECMO weaning failure in patients on VA-ECMO support for circulatory failure.MethodsAll patients who underwent VA-ECMO in our hospital for CS between January 2017 and December 2020 were recruited in this cohort study and divided into two groups: without and with levosimendan use. Levosimendan was used as an add-on to other inotropic agents as early as possible after VA-ECMO setting. The primary endpoint was VA-ECMO weaning success, which was defined as survival without events for 24 h after VA-ECMO withdrawl. The secondary outcomes were cardiovascular and all-cause mortality at the 30-day and 180-day follow-up periods post-VA-ECMO initialization.ResultsA total of 159 patients were recruited for our study; 113 patients were enrolled in the without levosimendan-use group and 46 patients were enrolled in the levosimendan-use group. In levosimendan-use group, the patients received levosimendan infusion within 24 h after VA-ECMO initialization. Similar hemodynamic parameters were noted between the two groups. Poorer left ventricular ejection fraction and a higher prevalence of intra-aortic balloon pumping were observed in the levosimendan group. An improved weaning rate (without vs. with: 48.7 vs. 82.6%; p < 0.001), lower in-hospital mortality rate (without vs. with: 68.1 vs. 43.5%; p = 0.007), and 180-day cardiovascular mortality (without vs. with: 75.3 vs. 43.2%; p < 0.001) were also noted. Patients administered with levosimendan also presented a lower rate of 30-day (without vs. with: 75.3 vs. 41.3%; p = 0.034) and 180-day (without vs. with: 77.0 vs. 43.2%; p < 0.001) all-cause mortality.ConclusionEarly levosimendan administration may contribute to increasing the success rate of VA-ECMO weaning and may help to decrease CV and all-cause mortality.

Effect of levosimendan infusion prior to left ventricular assist device implantation on right ventricular failure

ObjectiveInvestigate the safety and efficacy of preoperative levosimendan in patients undergoing left ventricular assist device (LVAD) implantation.MethodsConsecutive patients who received LVADs (HeartMate-2, 3, HVAD) in a single tertiary medical center (2012–2018). INTERMACS profile 1 patients were excluded. The primary outcome was post-LVAD right ventricular failure (RVF) and inhospital mortality rates. The secondary outcomes included other clinical, echocardiographic and hemodynamic parameters at follow-up.ResultsFinal cohort consisted of 62 patients (40[65%] in the levosimendan group and 22[35%] in the no-levosimendan group). Post-operative RVF rate and inotrope or ventilation support time were similar in the levosimendan and no-levosimendan groups (7.5% vs. 13.6%; P = 0.43, median of 51 vs. 72 h; P = 0.41 and 24 vs. 27 h; P = 0.19, respectively). Length of hospitalization, both total and in the intensive care unit, was not statistically significant (median days of 13 vs. 16; P = 0.34, and 3 vs. 4; P = 0.44, respectively). Post-operative laboratory and echocardiographic parameters and in-hospital complication rate did not differ between the groups, despite worse baseline clinical parameters in the Levosimendan group. There was no significant difference in the in-hospital and long term mortality rate (2.5% vs. 4.5%; P > 0.999 and 10% vs. 27.3% respectively; P = 0.64).ConclusionsLevosimendan infusion prior to LVAD implantation was safe and associated with comparable results without significant improved post-operative outcomes, including RVF.

Levosimendan's effect on venoarterial extracorporeal membrane oxygenation weaning.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) provides temporary haemodynamic support in refractory cardiogenic shock. Recent retrospective studies on levosimendan on V-A ECMO weaning had conflicting results. This study aimed to determine the association between levosimendan on V-A ECMO weaning success in a tertiary centre in Hong Kong. This retrospective study was conducted in an intensive care unit in Hong Kong. All adult patients requiring V-A ECMO from January 2016 to September 2020 were included. Patients who were given levosimendan were compared to patients who were not, on rates of successful V-A ECMO weaning. The groups were also compared after propensity matching based on covariates closely associated with the use of levosimendan. A total of 119 patients were included in the study, with 38 in the levosimendan group and 81 in the non-levosimendan group. Patients treated with levosimendan trended towards improved weaning success, but the difference was not statistically significant (63% vs 53%, p = 0.404). In the propensity-matched groups, there was no difference in weaning success (odds ratio 1.00, 95% CI 0.23-8.00). The levosimendan group was associated with lower vasopressor requirement, lower lactate levels, and more significant drop in lactate in the first 2 days of V-A ECMO. The levosimendan group had longer ECMO duration. There was no difference in other secondary outcomes including mortality, length of stay in ICU and hospital and duration of mechanical ventilation. There was no difference in the rate of ventricular arrhythmias. Levosimendan did not improve V-A ECMO weaning success in our cohort with refractory cardiogenic shock.

The Use of Levosimendan after Out-of-Hospital Cardiac Arrest and Its Association with Outcome-An Observational Study.

Background: Levosimendan improves resuscitation rates and cardiac performance in animal cardiac arrest models. The aim of this study was to describe the use of levosimendan in out-of-hospital cardiac arrest (OHCA) patients and its association with outcome. Methods: A retrospective observational study of OHCA patients admitted to six intensive care units in Stockholm, Sweden, between 2010 and 2016. Patients treated with levosimendan within 24 h from admission were compared with those not treated with levosimendan. Propensity score matching and multivariable logistic regression analysis were used to assess the association between levosimendan treatment and 30-day mortality Results: Levosimendan treatment was initiated in 94/940 (10%) patients within 24 h. The proportion of men (81%, vs. 67%, p = 0.007), initial shockable rhythm (66% vs. 37%, p < 0.001), acute myocardial infarction, AMI (47% vs. 24%, p < 0.001) and need for vasoactive support (98% vs. 61%, p < 0.001) were higher among patients treated with levosimendan. After adjustment for age, sex, bystander cardiopulmonary resuscitation, witnessed status, initial rhythm and AMI, the odds ratio (OR) for 30-day mortality in the levosimendan group compared to the no-levosimendan group was 0.94 (95% Confidence interval [CI], 0.56–1.57, p = 0.82). Similar results were seen when using a propensity score analysis comparing patients with circulatory shock. Conclusions: In this observational study of OHCA patients, levosimendan was used in a limited patient group, most often in those with initial shockable rhythms, acute myocardial infarction and with a high need for vasopressors. In this limited patient cohort, levosimendan treatment was not associated with 30-day mortality. However, a better matching of patient factors and indications for use is required to derive conclusions on associations with outcome.

The evaluation of levosimendan in patients with acute myocardial infarction related ventricular septal rupture undergoing cardiac surgery: a prospective observational cohort study with propensity score analysis

Study objectiveThe purpose of the present study was to evaluate the efficacy of levosimendan in patients with acute myocardial infarction related ventricular septal rupture (AMI-VSR) underwent cardiac surgery.DesignProspective observational cohort study with propensity score analysis.PatientsThere were 261 patients with AMI-VSR in our study. After 1:1 propensity matching, 106 patients (53 levosimendan and 53 control) were selected in the matched cohort.InterventionsNone.MeasurementsPatients who received levosimendan were assigned to the levosimendan group (n = 164). The patients who were not received were levosimendan assigned to the control group (n = 97). The levosimendan was initiated immediately after cardiopulmonary bypass. Then, it has been maintained during the postoperative 3 days. The poor outcomes were identified as follows: death and postoperative complications (postoperative stroke, low cardiac output syndromeneeded mechanical circulatory support after surgery, acute kidney injury (≥ stage III), postoperative infection or septic shock, new developed atrial fibrillation or ventricular arrhythmias).Main resultsBefore matching, the control group had more length of ICU stay (6.69 ± 3.90 d vs. 5.20 ± 2.24 d, p < 0.001) and longer mechanical ventilation time (23 h, IQR: 16–53 h vs. 16 h, IQR: 11–23 h, p < 0.001). Other postoperative outcomes have not shown significant differences between two groups. After matching, no significant difference was found between both groups for all postoperative outcomes. The Kaplan–Meier survivul estimate and log-rank test showed that the 90-day survival had no significant differences between two groups before and after matching.ConclusionOur study found that a low-dose infusion of levosimendan in AMI-VSR patients underwent surgical repair did not associated with positively affect to postoperative outcomes.

Exercise Capacity Is Improved by Levosimendan in Heart Failure and Sarcopenia via Alleviation of Apoptosis of Skeletal Muscle.

BackgroundPatients suffering from chronic heart failure (CHF) show an increased prevalence of sarcopenia. Levosimendan is an effective drug for the treatment of heart failure, but its effect on sarcopenia is still unclear. We aimed to explore whether levosimendan could enhance skeletal muscle contractibility, improve skeletal muscle atrophy, and thus improve exercise tolerance of individuals with heart failure.MethodsC57BL6/J mice were used to establish the heart failure with sarcopenia model and injected of levosimendan. Mice were separated into control group, sham operation group, HF group, HF + solvent group, HF + levosimendan group, HF + sarcopenia group, HF + sarcopenia + solvent group, HF + sarcopenia + levosimendan group (n = 5–12). After the treatment, exercise capacity and cardiac function were evaluated. Muscle morphology, inflammation level and apoptosis levels were detected, in which mitochondrial function and oxidative stress level were also assessed.ResultLevosimendan could increase forelimb grip strength/body weight, hanging impulse, maximum running distance and time in mice with HF and sarcopenia (P < 0.0001 for all), and these improvements were independent of EF (P = 0.0019 for hanging impulse, P < 0.001 for forelimb grip strength/body weight and maximum running distance). Levosimendan directly increased the CSA of gastrocnemius in mice with HF and sarcopenia (P < 0.0001). After levosimendan injection, the proportion of slow muscle fibers increased (P < 0.0001), but this improvement of muscle fiber typing might be attributed to improved cardiac function (P > 0.05). Levosimendan also maintained mitochondrial membrane potential, decreased cleaved caspase-3 (P = 0.034), cleaved caspase-9 (P < 0.0001), Bax expression (P < 0.0001), and increased Bcl2 expression (P = 0.0036). This effect is independent of improved cardiac function (P = 0.028 for bax, P < 0.001 for cleaved caspase-9 and Bcl2). IL-6, TNF-α expression (P < 0.0001 for both) decreased, and SOD activity (P = 0.0038), GSH/GSSG ratio (P = 0.002) significantly increased in skeletal muscle after injection of levosimendan. The improvement in oxidative stress level was attributed to improved cardiac function (P > 0.05).ConclusionLevosimendan reduce the loss of skeletal muscle mitochondrial membrane potential, decrease the apoptosis, alleviate the inflammation and oxidative stress, and ultimately improve the exercise capacity of mice with heart failure and sarcopenia. Therefore, levosimendan may be a potential drug for the treatment of heart failure with sarcopenia.

Yüksek Riskli Koroner Arter Hastalarında Profilaktik Levosimendan Kullanımı: Retrospektif Klinik Araştırma

Objective: To investigate the perioperative and postoperative effects of preoperative levosimendan use in coronary artery patients with low ejection fraction (EF) (<40%). Material and Methods: A total of 6,571 coronary bypass patients who were treated at Kartal Koşuyolu High Specialization Training and Research Hospital between 2016 and 2019 were scanned, and 132 patients with preoperative EF below 40% were retrospectively analyzed. The patients were divided into 2 groups as those who received preoperative levosimendan (Group 1: 90 patients) and the control group, who did not receive it at all (Group 2: 42 patients). All of the patients included in the study were onpump coronary bypass patients and excluded off-pump bypass, emergency bypass, and other concomitant procedures. Results: In terms of EF values, improvements over time were significantly different in favor of Group 1 (p<0.043). The duration of the intensive care unit stay in Group 1 was longer (p<0.047). The changes in patients in terms of postoperative venous oxygen saturation over time were found to be statistically positive in favor of Group 1 (p<0.042). Mortality was observed in 5 patients in the postoperative early period (first 30 days), all of whom were from Group 1. However, no statistical difference was observed. Conclusion: Preoperative use of levosimendan in coronary artery patients with low EF improved some hemodynamic parameters; however, it did not make a significant hemodynamic and clinical contribution to surgery success in high-risk patients.

The effect of levosimendan on right ventricular function in patients with heart dysfunction: a systematic review and meta-analysis

Levosimendan exerts positive inotropic and vasodilatory effects. Currently, its effects on right heart function remain uncertain. This systematic review and meta-analysis is intended to illustrate the impacts of levosimendan on systolic function of the right heart in patients with heart dysfunction. We systematically searched electronic databases (PubMed, the Cochrane Library, Embase and Web of Science) up to November 30, 2020, and filtered eligible studies that reported the impacts of levosimendan on right heart function. Of these, only studies whose patients suffered from heart dysfunction or pulmonary hypertension were included. Additionally, patients were divided into two groups (given levosimendan or not) in the initial research. Then, RevMan5.3 was used to conduct further analysis. A total of 8 studies comprising 390 patients were included. The results showed that after 24 h of levosimendan, patients’ right ventricular fractional area change [3.17, 95% CI (2.03, 4.32), P < 0.00001], tricuspid annular plane systolic excursion [1.26, 95% CI (0.35, 2.16), P = 0.007] and tricuspid annular peak systolic velocity [0.86, 95% CI (0.41, 1.32), P = 0.0002] were significantly increased compared to the control group. And there is an increasing trend of cardiac output in levosimendan group [1.06, 95% CI (− 0.16, 2.29), P = 0.09 ] .Furthermore, patients’ systolic pulmonary arterial pressure [− 5.57, 95% CI (− 7.60, − 3.54), P < 0.00001] and mean pulmonary arterial pressure [− 1.01, 95% CI (− 1.64, − 0.37), P = 0.002] were both significantly decreased, whereas changes in pulmonary vascular resistance [− 55.88, 95% CI (− 206.57, 94.82), P = 0.47] were not significant. Our study shows that in patients with heart dysfunction, levosimendan improves systolic function of the right heart and decreases the pressure of the pulmonary artery.

The Effect of Levosimendan on Phosphine-Induced Nephrotoxicity: Biochemical and Histopathological Assessment.

Aluminum phosphide (AlP) toxicity is associated with a high risk of death due to heart, liver, and kidney failure as the target organs. Phosphine gas released due to the ingestion is the main factor involved in the multi-organ failure with various mechanisms. Levosimendan (LEV) is a calcium sensitizer with a pleiotropic effect on multiple organs. This study aimed to investigate whether LEV can alleviate AlP-induced nephrotoxicity in the rat model. Six groups included control group (almond oil only), sole LEV group (48 µg/kg), AlP group (LD50=10 µg/kg), and the poisoned groups treated with LEV at doses of 12, 24, and 48 µg/kg 30 min after AlP gavage. After 24 hours of treatment, serum and kidney samples were taken for biochemical and histopathological analyses. Biochemical analysis of the AlP group showed that the activity of complexes I, II, and IV was significantly reduced, while the levels of lipid peroxidation (LPO) and reactive oxygen species (ROS), lactate, and myeloperoxidase (MPO) activity significantly increased. Also, AlP reduced live renal cells and elevated necrosis. However, the levels of serum creatinine and blood urea nitrogen were not affected by the poisoning. LEV co-treatment could increase mitochondrial complex activity and reduce MPO activity, LPO, ROS, and lactate levels. Additionally, the histopathological analysis showed the detrimental effects of AlP on kidney tissue, which was mitigated by LEV administration. Our findings showed that LEV can potentially improve oxidative stress, imbalance in the redox status, necrosis, and pathological injuries in kidney tissue following AlP-poisoning.