Levosimendan Group Research Articles

Inodilators in acute heart failure: what about the right ventricle?

Abstract Objectives This research examines the impact of levosimendan on right ventricular (RV) function in patients with cardiovascular conditions, aiming to evaluate enhancements in crucial echocardiographic indicators of RV systolic performance. Methods A total of 54 patients hospitalized for acute heart failure were enrolled in the study and divided into two groups: 25 patients received 12.5 mg of levosimendan over 24 hours, while the remaining 29 patients served as the control group. Echocardiographic parameters were measured at baseline and after treatment for both groups. Results In the levosimendan group, the post-treatment S' tissue velocity increased significantly from 9.48 ± 1.06 cm/s to 10.43 ± 1.28 cm/s (p=0.025), whereas the control group exhibited a change from 9.31 ± 0.93 cm/s to 9.53 ± 1.11 cm/s. The fractional area change (FAC) showed a notable improvement in the levosimendan group from 20 ± 3% to 27 ± 2% (p < 0.0001), compared to a minor change in the control group. Tricuspid annular plane systolic excursion (TAPSE) significantly increased in the levosimendan group from 13.8 ± 0.4 mm to 15.6 ± 0.36 mm (p < 0.0001), while the control group displayed minimal change. Systolic pulmonary artery pressure (SPAP) reduction was more significant in the levosimendan group (from 58.67 ± 7.28 mmHg to 47.22 ± 5.6 mmHg) compared to the control group (from 60.5 ± 9.34 mmHg to 55.85 ± 7.41 mmHg) (p=0.012). Additionally, RV strain improved considerably in the levosimendan group from -20 ± 3% to -23 ± 3% (p=0.03), while the control group changed from -19 ± 3% to -20 ± 3%. Conclusion Levosimendan markedly enhances right ventricular function, as demonstrated by significant increases in S' velocity, FAC, RV strain, and TAPSE, along with a notable reduction in SPAP. These results indicate that levosimendan is a promising therapeutic agent for improving RV function.

Levosimendan improves the early prognosis of patients with Non ST-segment elevation myocardial infarction and Killip class > II

Abstract Background Levosimendan is an inotropic agent known for its calcium-sensitizing myofilament effect and ATP-dependent potassium channel opening mechanism, which enhances myocardial contractility without increasing oxygen consumption. Despite its potential benefits, the impact of levosimendan on the prognosis of patients with myocardial infarction remains uncertain and requires further investigation through larger-scale studies. Purpose This study aimed to investigate the effect of levosimendan on the short-term prognosis of patients with Non-ST-segment elevation myocardial infarction (NSTEMI) and Killip> II. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals in the City from 2010 to 2023. A total of 12472 patients with NSTEMI and Killip > II were included. Patients were divided into the levosimendan group and the non-leosimendan group based on whether levosimendan was used during hospitalization. Propensity score matching (PSM) was employed to balance covariates between the two groups. Multivariate Cox regression was used to evaluate the relationship between levosimendan and clinical outcomes. Covariates adjusted in PSM included age, sex, Killip class, early PCI, previous PCI, previous medical conditions (diabetes, hypertension, ischemic stroke, and chronic kidney disease), and medications during hospitalization (aspirin, clopidogrel, indobufen, ticagrelor, statins, cedilanid, recombinant human brain natriuretic peptide [rhBNP], milrinone, dopamine, dobutamine, and angiotensin converting enzyme inhibitor/angiotensin receptor blockers [ACEI/ARB]). The primary endpoint was major cardiovascular and cerebrovascular adverse events (MACCE), defined as the composite endpoint of cardiac death, myocardial infarction, and ischemic stroke within 3 months. Results The levosimendan group comprised 782 patients, while the non-leosimendan group included 11690 patients. After PSM, the covariates were balanced, resulting in 756 well-matched pairs. In PSM patients, the levosimendan group exhibited a significantly lower incidence of MACCE (aHR, 0.573; 95%CI, 0.466–0.704; p < 0.001) and cardiac death (aHR, 0.500; 95%CI, 0.399-0.626; p < 0.001). However, there was no significant difference in the incidence of myocardial infarction and ischemic stroke. Conclusions Levosimendan was associated with a lower incidence of MACCE within 3 months in patients with NSTEMI and Killip> II, mainly driven by lower incidence of cardiac death. However, these findings are based on observational data and require confirmation through adequately powered, randomized, controlled trials.

Levosimendan in Patients with Low Cardiac Output Syndrome After Cardiac Surgery: A Substudy of the Multicenter Randomized CHEETAH Trial

ObjectiveTo test the hypothesis that levosimendan administration to patients with low-cardiac-output syndrome after cardiac surgery is associated with improved long-term (5-year follow-up) outcome. DesignSingle-center subanalysis of the multicenter randomized CHEETAH trial. SettingCardiac surgery department of a tertiary hospital. ParticipantsA total of 134 adult patients requiring hemodynamic support for cardiac index <2.5 L/min/m2 after cardiac surgery with cardiopulmonary bypass (CPB). InterventionsPatients were randomized (1:1 ratio) to receive levosimendan (continuous infusion with starting dose of 0.05 μg/kg/min) or placebo, in addition to standard inotropic care. Measurements and Main ResultsThe primary endpoint was long-term mortality (1-5 years) after randomization. Secondary outcomes were the following: hemodynamic parameters, need for inotropic support (VIS), acute kidney injury (AKI), need for renal-replacement therapy, duration of mechanical ventilation, ICU and hospital stay, 30-day mortality. No significant between-group difference in long-term mortality (5-year) was observed (hazard ratio, 1.59; 95% CI, 0.81 to 3.11; P = 0.17). There were no significant differences in secondary outcomes, except for the difference in the mean pulmonary artery pressure at 4-6 hours after randomization, which was lower in the levosimendan group (24 [21.8, 28] mmHg versus placebo 26 [22.2, 33] mmHg, p = 0.019). ConclusionsAmong patients requiring hemodynamic support after cardiac surgery with CPB, perioperative levosimendan infusion does not affect long-term survival (1-5 years) compared with placebo. Levosimendan also had no effect on major clinical outcomes such as AKI, ICU stay, hospital stay, 30-day mortality.

The efficacy of levosimendan and dobutamine on reducing peripheral blood interleukin-6 levels and improving cardiac function in patients with septic cardiomyopathy: a comparative study.

In patients with severe septic cardiomyopathy, levosimendan has been found to improve myocardial contractility more effectively than dobutamine, although the underlying mechanisms remain unclear. This study aims to compare the effects of levosimendan and dobutamine on cardiac function and inflammatory markers in patients with septic cardiomyopathy, and to further investigate the advantages and disadvantages of both treatments. We included 40 patients with septic cardiomyopathy treated in the intensive care unit of our hospital from September 2020 to September 2023. The patients were randomly divided into a levosimendan group (n=20) and a dobutamine group (n=20). Plasma concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured by immunofluorescence at the start of treatment, 24 hours, and 48 hours. Cardiac troponin I (cTnI) concentrations were determined by chemiluminescence, and left ventricular ejection fraction (LVEF) was measured using the Simpson method. After 24 hours of treatment, there were no significant differences in IL-6, IL-1β, and TNFα levels between the two groups (P>0.05). However, at 48 hours, the IL-6 level in the levosimendan group was significantly lower than that in the dobutamine group (319.43±226.05 pg/ml vs. 504.57±315.20 pg/ml, P=0.039), while IL-1β and TNF-α levels showed no significant differences (P>0.05). Additionally, the cTnI level in the levosimendan group was significantly lower than that in the dobutamine group (1.01±0.54 ng/ml vs. 1.40±0.63 ng/ml, P=0.042), and LVEF was significantly higher in the levosimendan group (50.60±6.11% vs. 46.90±4.95%, P=0.042). These findings suggest that levosimendan may reduce plasma IL-6 levels, alleviate myocardial injury, and improve myocardial contractility in patients with septic cardiomyopathy compared to dobutamine.

Levosimendan versus Milrinone in Improving Pulmonary Hypertension after Cardiac Surgery

Abstract Background Pulmonary hypertension is a multifactorial disease with a high morbidity and mortality, right ventricular function is the most important predictor of morbidity and mortality in patients suffering from pulmonary hypertension. Milrinone, a phosphodiesterase III inhibitor is commonly used during post cardiopulmonary bypass (CPB) period in combination with adrenaline or noradrenaline to decrease pulmonary artery pressure and to provide synergistic positive inotropic effect. Levosimendan is a calcium sensitizing agent with inotropic, pulmonary vasodilatory, and cardioprotective properties. This study compared levosimendan with milrinone in improving pulmonary hypertension after cardiac surgeries. Objective To compare between levosimendan and milrinone in improving pulmonary hypertension after cardiac surgeries. Patients and Methods In this study 40 Patients were assigned randomly by using a computer – generated table of random numbers, placing them in sealed envelopes, into two groups: Group M: 20 Patients were received milrinone Group L:20 Patients were received levosimandan. Results In this study we compared levosimendan vs milrinone, in levosimendan group there was more significant increase of post operative TAPSE, in milrnone group there was more significant decrease of PAP and RVSP. There was statistically significant difference groups received milrinone in pre, post operative AST, ALT as there was increase in post operative AST and ALT, groups were compared in demographic data (in terms of age, sex, weight and height) and there was no statistically significant difference between groups, were compared as regard CPB and type of surgery and there was no statistically significant difference between groups, were compared in post operative data (in terms of systolic, diastolic blood pressure, heart rate, SPO2, CVP, UOP and extubation time), there was no statistically significant difference between groups, were compared in kidney function (in term of pre and post operative serum creatinine), there was no statistically significant difference between groups, were compared in acid base data (in term of post operative PH), there was no statistically significant difference between groups, were compared in weaning from ventilators (within 24 hours post operative) and there was no statistically significant difference between groups. Conclusion We concluded that in levosimendan group there was more significant increase in post operative TAPSI, in milrinone group there was more significant decrease of PAP and RVSP and in milrinone group there was increase in post operative AST/ALT.

The therapeutic effect of levosimendan in patients with prolonged ventilator weaning and cardiac dysfunction.

To explore the therapeutic effect of levosimendan in patients with prolonged ventilator weaning and cardiac dysfunction. Patients with prolonged ventilator weaning and cardiac dysfunction were randomly allocated to receive conventional treatment (control group) or intravenous infusion of levosimendan for 24 h based on conventional treatment (levosimendan group). Weaning success rates were then compared between the two groups. The study was retrospectively registered with Research Registry (ID No. researchregistry10304). A total of 40 patients were included (20 per group). Within 3 days after initiation of treatment, significantly more cases were successfully weaned in the levosimendan group versus control group (eight versus four cases, respectively). Among the eight patients who underwent pulse indicator continuous cardiac output monitoring in the levosimendan group, the global ejection fraction increased 24 h after treatment, and the cardiac function index and cardiac index increased 72 h after treatment. For patients requiring prolonged mechanical ventilation who have concomitant cardiac dysfunction, levosimendan may be considered to increase the probability of weaning success.

Protective effects of levosimendan in scopolamineinduced mice model of Alzheimer's disease

Objectives. Alzheimer's disease is the most prevalent neurodegenerative disease and accounts for approximately 70% of all dementia cases worldwide. Levosimendan is a positive inotropic agent with well-documented pleiotropic properties, including anti-inflammatory and antioxidant effects. The current research evaluated the possible effect of levosimendan alone or in combination with donepezil against scopolamine-induced mice models of Alzheimer’s disease. Material and methods. Mice were divided into five groups: the control group, the induction group (scopolamine 1 mg/kg/i.p once daily for 7 days), other groups that received the tested drugs prophylactically for 2 weeks and then induced with scopolamine together with the same doses of the tested drug for one week. These treatment groups included the levosimendan group (200 μg/kg i.p. once weekly for 3 weeks), the donepezil group (5 mg/kg i.p once daily for 3 weeks), and the fifth group received a combination of levosimendan (200 μg/ kg i.p. once weekly) and donepezil (5mg/kg i.p once daily). Cognitive performance was assessed by conducting behavioral tests (a novel objective recognition test and Y Maze test), and the levels of biological markers of oxidative stress (SOD and MDA), inflammatory cytokines (TNFα, IL1β and IL-6) and AChE in the brain tissue homogenate were measured utilizing available ELISA kits. Results. Levosimendan preserved the spatial memory and recognition function and significantly reduced: ACHE level, IL-6, IL-1β, TNF-α, and MDA levels, and significantly increased SOD level in mice brain tissue homogenate as compared to the induction group. And the combination of levosimendan with donepezil resulted in non-significant improvement as compared to each drug alone specifically in ACHE level reduction and oxidative stress markers. Conclusions. The current study showed that levosimendan produced a neuroprotective effect against the scopolamine-induced mice models of AD. This effect may be in part attributed to the antioxidant and anti-inflammatory properties of levosimendan.

Comparison of Levosimendan Versus Milrinone After the Arterial Switch Operation for Infants ≤3 kg.

Background: Various inotropes and inodilators have been utilized to treat low cardiac output syndrome after the arterial switch operation. The use of levosimendan, a calcium sensitizer has been limited in this setting. This study compares the effects of levosimendan with milrinone in managing low cardiac output after the arterial switch operation. Methods: A retrospective, comparative study was conducted in a tertiary care hospital on patients weighing up to 3 kg undergoing the arterial switch operation between January 2017 and January 2022. Patients received a loading dose followed by continuous infusion of either levosimendan or milrinone. Echocardiographic, hemodynamic and biochemical parameters were compared. Results: Forty-three patients received levosimendan and 42 patients received milrinone as the primary test drug. Cardiac index of less than 2.2 L/min/m2 on postoperative day 1 and 2 was found in 9.3% and 2.3% of patients receiving levosimendan versus 26.2% and 11.9% in those receiving milrinone, respectively (P = .04 and .08, respectively). Early lactate-clearance and better central venous oxygen saturations were noted in the levosimendan group. Prevalence of acute kidney injury was higher in the milrinone group (50% vs 28%; P = .03). Use of peritoneal dialysis in the milrinone group versus levosimendan was 31% and 16.3%, respectively (P = .11). There was no difference in hospital mortality between the groups (milrinone, 3; levosimendan, 2, P = .62). Conclusions: Levosimendan is safe and as effective as milrinone to treat low cardiac output syndrome occurring in neonates after the arterial switch operation. In addition we found that levosimendan was renal protective when compared with milrinone.

Comparative Effectiveness and Safety of Intermittent, Repeated, or Continuous Use of Levosimendan, Milrinone, or Dobutamine in Patients With Advanced Heart Failure: A Network and Single-Arm Meta-analysis.

The aim of this study was to synthesize the available evidence regarding differences in the long-term safety and efficacy of intermittent, repeated, or continuous palliative inotropic therapy among patients with advanced heart failure. We systematically searched the PubMed, Embase, and Cochrane Library electronic databases, with a cutoff date of November 23, 2023, for studies reporting outcomes in adult patients with advanced heart failure treated with intermittent, repeated, or continuous levosimendan, milrinone, or dobutamine. Forty-one studies (18 randomized controlled trials and 23 cohort studies) comprising 5137 patients met the inclusion criteria. The results of the network meta-analysis of randomized controlled trials showed that levosimendan had significant advantages over milrinone or dobutamine in reducing mortality and improving left ventricular ejection fraction. A single-arm meta-analysis also indicated that levosimendan had the lowest mortality and significantly improved B-type brain natriuretic peptide and left ventricular ejection fraction. Regarding safety, hypotension events were observed more frequently in the levosimendan and milrinone groups. However, the current evidence is limited by the heterogeneity and relatively small sample size of the studies.

The effect of histidine-tryptophan-ketoglutarate cardioplegia alone or combined with preoperative infusion of levosimendan on vasoactive inotropic score in patients with poor cardiac function undergoing coronary artery bypass grafting

ABSTRACT Background: Patients with poor left ventricular function undergoing cardiac surgery frequently require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan is an effective agent that acts via two complementary mechanisms. It enhances cardiac contractility and reduces cardiac workload. Aim: to assess the effect of histidine-tryptophan-ketoglutarate cardioplegia (HTK cardioplegia) alone or combined with preoperative infusion of levosimendan on the vasoactive inotropic score in patients with poor left ventricular function undergoing coronary artery bypass grafting. Material and method: this double-blinded randomized controlled trial was carried on 100 patients, divided into two groups; Levosimendan group (n = 49): patients received 0.1ug/kg/min levosimendan without loading, 12 hours preoperatively and continued for a total of 24 hours. Control group (n = 51): patients received a placebo 12 hours before surgery and continued for a total 24 hours. Both groups received HTK cardioplegia after cross-clamping of the aorta approximately 20 ml/kg into the ascending aorta over 6–8 minutes at a temperature of 4−10°C. Results: Levosimendan group was superior to control group with statistical significance regarding the need of intraaortic balloon pump (IABP), vasoactive inotropic score over the first 24 hours, troponin levels over the first 72 hours, ICU stays, hospital stay, and cumulative hospital costs. Although the incidence of postoperative low Cardiac output syndrome (LCOS), atrial fibrillation (AF), acute kidney injury (AKI), and overall mortality was lower in levosimendan group, but all were not statistically significant. Conclusion: Preoperative infusion of levosimendan combined with HTK cardioplegia in patients with poor cardiac function decreased vasoactive inotropic score and lowered the costs of hospital stay.

The association between levosimendan and mortality in patients with sepsis or septic shock: a systematic review and meta-analysis.

Levosimendan is increasingly being used in patients with sepsis or septic shock because of its potential to improve organ function and reduce mortality. We aimed to determine if levosimendan can reduce mortality in patients with sepsis or septic shock via meta-analysis. We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception through 1 October 2022. Literature evaluating the efficacy of levosimendan in patients with sepsis or septic shock was included. Two reviewers extracted data and assessed study quality. A meta-analysis was performed to calculate an odds ratio (OR), 95% confidence intervals (CI), and P -values for 28-day mortality (primary outcome). Secondary outcomes included changes in indexes reflecting cardiac function before and after treatment, changes in serum lactate levels in the first 24 h of treatment, and the mean SOFA score during the study period. Safety outcomes included rates of tachyarrhythmias and total adverse reactions encountered with levosimendan. Eleven randomized controlled trials were identified, encompassing a total of 1044 patients. After using levosimendan, there was no statistical difference between groups for 28-day mortality (34.9% and 36.2%; OR: 0.93; 95% CI [0.72-1.2]; P = 0.57; I 2 = 0%; trial sequential analysis-adjusted CI [0.6-1.42]) and sequential organ failure assessment (SOFA) score, and more adverse reactions seemed to occur in the levosimendan group, although the septic shock patient's heart function and serum lactate level improved. There was no association between the use of levosimendan and 28-day mortality and SOFA scores in patients with septic shock, though there was statistically significant improvement in cardiac function and serum lactate.

Repetitive LevosimenDan infusions fOR patients with advanced chronic heart failure in the vulnerable post-discharge period: the multinational randomized LeoDOR trial

Abstract Background Studies of the repetitive use of intravenous levosimendan suggested a beneficial effect in patients with advanced heart failure (HF). It was the aim of the LeoDOR trial to test the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute HF. Methods In this multicenter, double-blind, three-armed trial with an enrolment period from 3-2018 to 6-2021, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or placebo for a period of 12 weeks. Levosimendan was administered according to center preference either as 6-hour infusion at a rate of 0.2 mcg/kg/min every 2 weeks, or as 24-hour infusion at a rate of 0.1 mcg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank endpoint consisting of three hierarchical groups: Tier 1 = time to death or urgent heart transplantation or implantation of a ventricular assist device; Tier 2 = time to non-fatal HF requiring i.v. vasoactive therapy; Tier 3 = time-averaged proportional change in NTproBNP from baseline to week 14. Results Due to a forced interim interruption of the study as a result of the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat (mITT) analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm). Patient characteristics were well balanced between treatment and placebo arms (mean age 69.3±9.7 vs 67.9±10.1, proportion of women 22.6% vs 21.2%, HF-hospitalizations in previous 12 months 1.9±1.4 vs. 1.7±1.1, NTproBNP at baseline 4740 ng/L (IQR 2235 – 9016) vs 5380 ng/L (IQR 2287 – 8204). There were no marked differences regarding HF medication and implanted devices. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint (mean rank score 71.8 for the levosimendan group vs 75.1 for the placebo group; p = 0.65). However, there was a strong signal towards a higher incidence of the individual clinical components of the primary endpoint (tier 1 plus tier 2) in the levosimendan group vs the placebo group both after 14 weeks (HR 2.94, 95%CI 1.13–7.70; p = 0.028) and 26 weeks (HR 1.65 95%CI 0.87 – 3.12; p = 0.123). The number of investigator-reported adverse events during and immediately after drug application was 12.4% in the levosimendan group vs 11.8% in the placebo group (p = 0.905). Conclusion Our findings do not support the use of intermittent levosimendan to improve post-hospitalization clinical stability in patients who were recently hospitalized with HF and reduced LVEF. Further studies are warranted to find the correct use of levosimendan in advanced heart failure patients.

Levosimendan In Cardiology and Cardiac Surgery

Introduction: levosimendan is an inodilator successfully used in the treatment of acute and chronic heart failure. Its use in the treatment of low cardiac output syndrome pre- and postoperatively after cardiac surgery under extracardiac circulation is poorly documented, but it appears to be a very interesting alternative in terms of morbimortality. Aim of the study: to evaluate the value of levosimendan versus dobutamine in the rapid weaning of inotropic drugs in low output patients awaiting cardiac surgery and after surgery under extracorporeal circulation. Materials and methods: sixty patients with low cardiac output syndrome before surgery on levosimendan and after cardiac surgery on extracorporeal circulation, requiring positive inotropic and vasopressor drugs (dobutamine ± noradrenaline). Post-operatively, in the context of drug weaning, we identified two groups : levosimendan group (n=30) and dobutamine group (n=30). In the levosimendan group, dobutamine was replaced immediately postoperatively by levosimendan. Hemodynamic parameters (MAP, HR, CI, ESV, SVR), ICU length of stay and 30-day mortality were assessed and compared between the two groups of patients. Results: Cardiac index was significantly higher in the levosimendan group than in the dobutamine group (2.8 [0.3] l/min/m² versus 2.3 [0.4] ml/min/m²) respectively, P Conclusion: the use of levosimendan in the treatment of low cardiac output syndrome before and after cardiac surgery with extracorporeal circulation resulted in rapid improvement in hemodynamic status with a short intensive care unit stay and low mortality.

Comparison between Levosimendan versus Beta Agonists in Preservation of Renal Function in Cardiac Surgery Patients with Low Cardiac Output Syndrome

Abstract Background Acute kidney injury post cardiac surgery in patients who develop low cardiac output syndrome (LCOS) postoperatively is a serious complication. Many studies have been performed to assess the effect of inotropic agents on cardiac function when administered postoperatively, some studies performed to evaluate the nephroprotective effect of conventional inotropic agents as compared to levosimendan. Objective To evaluate the possible nephroprotective effect of Levosimendan as compared to betaagonists in cardiac surgery patients with LCOS. Patients and Methods It is a randomized prospective comparative study at Ain Shams university hospitals from December 2020 to May 2021. A total of 60 patients who have developed low cardiac output syndrome post cardiac surgery divided into two groups of 30 patients each. Group A received beta-agonists (dobutamine 2 - 20 µ/kg/min or adrenaline 0.01 to 0.5 mcg/kg/minute) and Group B received levosimendan for 24 h at a rate of 0.1 mcg/kg/min to a target dose of 12.5 mg. we assessed the incidence of renal failure in these patients. We assessed the progress of acute kidney injury in patients who developed acute renal impairment at diagnosis of LCOS in both treatment groups. Parameters assessed include hemodynamics and renal function parameters. Results The incidence of acute kidney injury 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 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%. Conclusion Levosimendan has a nephroprotective effect that plays a role in preservation of renal functions and decreasing the incidence of kidney failure in patients with LCOS post cardiac surgery as compared to beta – agonists.

Preoperative Levosimendan Administration in Heart Transplant Patients with Severe Hepatic and Renal Impairment: A Retrospective Study.

The cardio-renal syndrome and hepatic impairment play a critical role in end-stage heart failure (HF). Levosimendan is an effective inotropic agent used to maintain cardiac output similar to classic cardiotonic like dobutamine/dopamine. This current research aims to investigate the clinical outcomes of levosimendan and dobutamine/dopamine in Chinese heart transplant awaiting patients with severe hepatic or renal impairment. We performed a retrospective analysis of 568 heart transplant awaiting individuals with severe hepatic or renal impairment who treated with levosimendan or dobutamine/dopamine in our institution between January 2015 and December 2020. Univariate Cox proportional hazard models and Kaplan-Meier survival curves were applied. The primary endpoint was defined as death included inhospital mortality and the mortality at 30 days, 90 days, 180 days and 1 year after heart transplantation. There were no significant differences in mortality rate at 30, 90, 180 days and 1 years after heart transplantation between the levosimendan and non-levosimendan groups, or between subgroups of patients with severe hepatic impairment or renal impairment. The results were consistent before and after propensity score matching. In the population with advanced heart failure awaiting heart transplantation, levosimendan did not increase short- or long-term mortality rates after surgery compared to dobutamine/dopamine, regardless of their hepatic or renal function. Severe hepatic or renal impairment were not necessarily considered a contraindication for levosimendan in these patients.

The Perioperative Use of Levosimendan as a Means of Optimizing the Surgical Outcome in Patients with Severe Heart Insufficiency Undergoing Cardiac Surgery.

Postoperative myocardial dysfunction following cardiac surgery is a relatively common occurrence. Levosimendan, a calcium sensitizer and inotropic drug, has shown potential in improving outcomes for patients with low preoperative ejection fraction (EF) and myocardial dysfunction after cardiac surgery. This study aims to evaluate the efficacy of levosimendan in optimizing the surgical outcome for such patients. A retrospective analysis was conducted on 314 patients with preoperative severe heart failure who underwent cardiac surgery. Among them, 184 patients received perioperative adjunctive therapy with levosimendan, while a comparable group of 130 patients received conventional treatment. The use of levosimendan demonstrated several advantages in postoperative outcomes. It significantly improved short- and long-term survival rates after cardiac surgery, enhanced hemodynamic stability, reduced the requirement for inotropic support, and facilitated faster weaning from ventilator support. Patients who received levosimendan reported reduced angina and dyspnea symptoms, as well as fewer postoperative arrhythmias. Furthermore, levosimendan helped minimize myocardial injury inevitable after cardiac surgery. The levosimendan group also exhibited a notable reduction in hospital readmissions. This study provides evidence of several benefits associated with the perioperative use of levosimendan. However, further prospective randomized studies are warranted to standardize and comprehensively document the other perioperative therapies, in order to validate these findings and establish stronger conclusions.

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.

The anti-inflammatory and haemodynamic effects of levosimendan on advanced heart failure patients: a meta-analysis of published studies

Objective Increasing evidence from randomized controlled trials shows the anti-inflammatory and haemodynamic effects of levosimendan in advanced heart failure (AdHF), however, conflicting results have been reported in some studies. The aim of this study was to estimate the anti-inflammatory and haemodynamic effects of levosimendan on AdHF (registration number: INPLASY202250097). Methods The MEDLINE, PubMed, ClinicalTrials.com and Cochrane Library databases were systematically searched for studies published in English up to April 2019. Data were extracted from applicable articles. Meta-analyses were performed to assess interleukin (IL)-6, cardiac index, pulmonary artery pressure (PAP) and New York Heart Association (NYHA) functional class efficacy outcomes, following PRISMA 2020 guidelines. Results A total of 11 studies were included (211 patients who received levosimendan and 193 controls). Meta-analyses showed that the levosimendan group displayed significantly reduced IL-6 (standardized mean difference [SMD] −1.05; 95% confidence interval [CI] −1.44, −0.66; I2 = 50.9%), improved cardiac index (SMD 0.59; 95% CI 0.29, 0.88; I2 = 0.0%); reduced PAP (SMD −1.22; 95% CI −1.91, −0.53; I2 = 89.7%) and improved NYHA functional class (SMD −1.66; 95% CI −2.27, −1.04; I2 = 74.6%) versus controls. Conclusions Levosimendan infusion was beneficial in patients with AdHF, displayed by anti-inflammatory and improved haemodynamic effects, and improved NYHA functional class.

Levosimendan in the Treatment of Patients with Severe Septic Cardiomyopathy.

(1) Background: The optimal treatment of septic cardiomyopathy (SCM) remains questionable. The aim of the study was to compare the treatment of SCM based on levosimendan versus the best available therapy. (2) Methods: We conducted an observational study including patients with severe septic cardiomyopathy and circulatory failure. (3) Results: Fourteen patients (61%) received levosimendan, and nine received other treatments. The patients in the levosimendan group were more severely ill [APACHE II: 23.5 (14, 37) vs. 14 (13, 28), respectively, p = 0.012], and there was a trend for more decompensated LV function depicted by the LVEF [15% (10, 20) vs. 25% (5, 30), respectively, p = 0.061]. However, they presented a significantly higher increase in LVEF after seven days [15% (10, 20) to 50% (30, 68) (p < 0.0001) vs. 25% (5, 30) to 25% (15, 50) (p = 0.309), and a significantly higher decrease in lactate levels during the first 24 h [4.5 (2.5, 14.4) to 2.85 (1.2, 15), p = 0.036 vs. 2.9 (2, 18.9) to 2.8 (1, 15), p = 0.536]. Seven-day survival (64.3% vs. 33.3%, p = 0.424) and ICU survival (50% vs. 22.2%, p = 0.172) were higher in the first group, although differences did not reach statistical significance. The degree of left ventricular impairment and the magnitude of EF improvement by the seventh-day post-SCM onset were associated with mortality in regression analysis. (4) Conclusions: Our study presents main hemodynamic data supporting the possible efficacy of levosimendan treatment in patients with severe SCM.

Hematological effects of Levosimendan therapy in patients with heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Levosimendan is an inotropic drug, acting as calcium sensitizer, used in the management of acute heart failure. Despite its hemodynamic benefits, Levosimendan is associated with several adverse reactions, including hematological effects, with a hemoglobin value decrease, causing anemia. Acute coronary syndromes (ACS) might be a precipitant of acute heart failure, in a substantial proportion of cases. These situations may require the use of inotropic drugs, such as Levosimendan. Antithrombotic therapy is the cornerstone therapy for management of acute coronary syndromes, and the decision of which strategy is determined by the balance of ischemic and hemorrhagic risks. Therefore, in the management of acute heart failure, associated with ACS, the use of Levosimendan might be associated with the increase of hemorrhagic risk, due to hemoglobin decrease, influencing the antithrombotic therapy strategy choice. Purpose This study aims to evaluate the effect of the use of Levosimendan on the hemoglobin value, comparing with Dobutamine, in patients hospitalized for ACS. Methods We analyzed a retrospective, multicenter, observational cohort of 317 patients, admitted for ACS, requiring inotropic therapy. The population was divided into two groups: a group that used Levosimendan and a group that used Dobutamine. The mean decrease in hemoglobin value, and the minimum hemoglobin value, during hospitalization, was compared between both groups. Results Levosimendan sample included 39 patients, of which 40,1% (n=15) were women, with a mean age of 83±12,1 year old, while Dobutamine sample had 278 elements, of which 38% (n=105) were women with a mean age of 82±12,1. There was no statistically significant difference between both samples on age and sex distribution. Levosimendan group had a mean minimum hemoglobin value of 10,7±2,2 g/dL and a mean decrease in hemoglobin value, during hospitalization, of 2,7±1,9 g/dL, while Dobutamine group had a mean minimum hemoglobin value of 10,7±2,2 g/dL and a decrease in hemoglobin value, during hospitalization, 2,1±1,9g/dL. There was no statically significant difference on mean minimum hemoglobin value on both samples (p&amp;gt;0,05), however, there was a statistically significant difference, with a higher decrease in mean hemoglobin value, during hospitalization in patients using Levosimendan, comparing with patients using Dobutamine (2,7±1,9g/dL vs 2,1±1,9g/dL, p=0,04). Conclusion Levosimendan is associated with a higher decrease in hemoglobin value. As heart failure might complicate ACS episode, and might require inotropic therapy, we should be aware that the choice of using Levosimendan in these situations may confer a greater risk of bleeding, associated with the higher decrease in hemoglobin value, in patients who need intense antithrombotic therapy.