Efficacy Of Levosimendan Research Articles

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.

Unlocking the Therapeutic Symphony: A Systematic Review Exploring the Role of Levosimendan in the Management of Heart Failure.

Levosimendan, a novel drug, a calcium-sensitizing inotrope, has emergedas a potential therapeutic modulator for heart failure (HF). This review appraises the efficacy and safety of levosimendan in managing HF, in different clinical settings. The study aims to examine the clinical outcomes reported in the selected trials to determine the effectiveness of levosimendan in improving key parameters related to HF. Seven relevant studies encompassing 1200 participants were identified from three databases. Inclusion criteria included clinical trials that investigated the therapeutic efficacy of levosimendan in the treatment of HF, and studies involving both adult and pediatric participants. Exclusion criteria involved studies with insufficient data, studies other than clinical trials, case reports, letters to the editor, conference papers, grey literature, and studies published in a language other than English. Upon evaluating the included studies, it was found that levosimendan shows improved hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy. Levosimendan enhanced right ventricular (RV) function in patients with RV dysfunction after mitral valve (MV) surgeries and decreased the amount of N-terminalpro-B-typenatriuretic peptide (NT-ProBNP) innon-ST elevated myocardial infarction (NSTEMI) patients with elevated NT-proBNP, all without increasing the overall cost or duration of hospitalization. Despite variations in study designs and participant characteristics, evidence suggests levosimendan significantly improves left ventricular ejection fraction (LVEF) and exercise tolerance measured by a six-minute walk distance. Notably, its safety profile appears favorable with minimal arrhythmic events and comparable rates of adverse effects to a placebo. This systematic review highlights levosimendan's promising potential for HF management, warranting further research to solidify its clinical role.

Safety and efficacy of levosimendan in patients with cardiac amyloidosis

BackgroundPatients with cardiac amyloidosis (CA) often experience heart failure (HF) episodes. No evidence is available on inotropic therapy. This study aims to fill this gap by examining the safety and efficacy of levosimendan. MethodsWe retrieved all HF patients receiving ≥1 levosimendan infusion from 2013 to 2023. CA patients were matched with HF patients without CA (controls) based on sex, age, and left ventricular ejection fraction (LVEF). The response to levosimendan was measured as changes in daily urinary output, body weight, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR). ResultsCA patients (median age 77 years, 73% men, 59% with ATTR-CA) and controls were compared. Levosimendan infusion was stopped because of hypotension in 2 cases with CA and (in 1 case) worsening renal function, and in 2 controls because of ventricular tachycardia episodes and (in 1 case) hypotension. CA patients showed a trend toward increased daily urinary output (p = 0.078) and a significant decrease in body weight (p < 0.001), without significant changes in NT-proBNP (p = 0.497) and eGFR (p = 0.732). Both CA patients and controls displayed similar changes in urinary output, weight, and eGFR, but NT-proBNP decreased more significantly among controls (p < 0.001). No differences were noted in rehospitalization rates, but CA patients experienced higher mortality at 6 and 12 months (p = 0.003 and p = 0.001, respectively). ConclusionsLevosimendan appears safe for CA patients needing inotropic support. The diuretic response and weight decrease during hospitalization were comparable between CA patients and matched HF patients, despite the greater mortality of CA patients after discharge.

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.

Efficacy of levosimendan vs its combination with magnesium sulphate on spinal cord protection in infants undergoing coarctectomy: A randomized controlled study

ABSTRACT Background and Objective Spinal cord ischemia with subsequent paraplegia secondary to aortic coarctation repair procedures is rare, but it has serious consequences that can affect quality of life. Infrared spectroscopy (NIRS) is used for non invasive spinal cord oxygenation monitoring to estimate cord perfusion and detect early cord ischemic changes. Several pharmacological agents have been used to improve cord perfusion, the main action of these agents is to improve regional/systemic perfusion and decrease ICP. In the current study, we studied magnesium sulphate and levosimendan for their vasodilating effect that might improve spinal cord perfusion as part of spinal cord protection. Methods Forty two infants undergoing aortic coarctectomy under general anaesthesia were registered in double blinded randomized controlled study, three groups were included; group C received i.v. saline, group L received levosimendan in loading dose 6ug/kg i.v. for 15 minutes then maintenance dose 0.1 ug/kg/min till end of surgery and group M received levosimendan in loading dose 6 ug/kg i.v. for 15 minutes then maintenance dose 0.1 ug/kg/min in combination with magnesium sulphate in loading dose 25 mg/kg i.v. for 15 minutes then maintenance dose 10 mg/kg/hr till the end of surgery. The vital signs and NIRS values assessed before, during and after clamping of aorta. Results All baseline demographic data were comparable among all groups except for height (cm), which was significantly lower in Group L compared to Group C (p = 0.013). NIRS values were comparable among the three groups throughout experimental protocol except after cross clamp at 20 minutes, where Group M was significantly higher compared to group C (P = 0.007).Heart rate, mean arterial blood pressure, total fluid intake, urine output, aortic cross clamp time and surgical time was comparable among all groups, were comparable among 3 studied groups. Conclusion Adding magnesium sulphate to levosimendan has showed improvement in spinal cord perfusion during cross clamping as monitored by NIRS when compared to use of levosimendan alone or placebo in coarctectomy operations without affecting hemodynamics.

Meta-Analysis of the Efficacy of Levosimendan in the Treatment of Severe Sepsis Complicated with Septic Cardiomyopathy.

Sepsis is a medical condition characterized by acute organ dysfunction and uncontrolled inflammation. Organ dysfunction in sepsis is the primary cause of mortality in patients with myocardial dysfunction. Levosimendan is a vasodilating and inotropic agent used in patients with acute heart failure and has resulted in decreased morbidity and mortality in these patients. Our main objective is to examine levosimendan's efficacy in treating severe sepsis complicated with septic cardiomyopathy. We systematically searched five databases, PubMed, Web of Science, Embase, Cochrane Library and BioMed Central, for articles and publications from their inception to 2023. Our study adopted the PICOS approach in identifying suitable publications during the systematic search. Inclusion criteria included randomized, controlled trials utilizing levosimendan in adult patients diagnosed with septic shock or severe sepsis. We excluded non-English publications and non-randomized controlled trials. The Newcastle-Ottawa scale (NOS) scale was used to assess the methodological quality, while the risk of bias was assessed through the Cochrane Risk of bias tool. All statistical analyses were performed using RevMan version 5.4. Eight studies met the eligibility criteria and were included in the analysis. There was a statistically significant positive effect on cardiac input in patients treated with levosimendan compared to those treated with dobutamine (p < 0.001). Similarly, there were positive effects on left ventricular ejection fraction (LVEF) (p < 0.001) and left ventricular stroke work index (LVSWI) (p < 0.001). We observed a significant reduction in mortality (p < 0.01) and serum levels of lactic acid (p < 0.01). Levosimendan is a calcium sensitizer associated with an influx of calcium ions and activation of ATP-dependent potassium channels that increases myocardial contractility contractions, enhances vasodilation and improves oxygen supply to the cells and tissues. Levosimendan is highly efficacious and safe in the management of sepsis and sepsis-induced cardiomyopathy.

Comparative Efficacy of Levosimendan, Ramipril, and Sacubitril/ Valsartan in Isoproterenol-induced Experimental Heart Failure: A Hemodynamic and Molecular Approach.

Cardiac ischemia-related myocardial damage has been considered a major reason for heart failure. We aimed to investigate the role of levosimendan (LEVO) in comparison to ramipril and sacubitril/valsartan (Sac/Val) in preventing damage associated with isoproterenol (ISO) induced myocardial infarction. Myocardial infarction was induced by injecting subcutaneous isoproterenol (5 mg/kg once for 7 consecutive days) to establish an experimental heart failure model. Simultaneously, LEVO (1 mg/kg/day), ramipril (3mg/kg/day) and Sac/Val (68 mg/kg/day) suspension were administered orally for four weeks. We observed a significant correlation between ISO-induced ischemia with cardiac remodeling and alterations in myocardial architecture. LEVO, ramipril, and Sac/Val significantly prevented lipid peroxidation and damaged antioxidant enzymes like superoxide dismutase, catalase, glutathione and thioredoxin reductase. We also observed their ameliorative effects in myocardium's cardiac hypertrophy, evidenced by reduced heart weight to body weight ratio and transforming growth factor β related collagen deposition. LEVO, ramipril, and Sac/Val also maintained cardiac biomarkers like lactate dehydrogenase, creatine kinase-MB, brain natriuretic peptide and cardiac Troponin-I, indicating reduced myocardial damage that was further demonstrated by histopathological examination. Decreased sarcoplasmic endoplasmic reticulum Ca2+ATPase2a and sodium-calcium exchanger-1 protein depletion after LEVO, ramipril, and Sac/Val administration indicated improved Ca2+ homeostasis during myocardial contractility. Our findings suggest that LEVO has comparable effects to ramipril, and Sac/Val in preventing myocardial damage via balancing oxidant-antioxidant system, decreased collagen deposition, reduced myocardial stress as well as improved Ca2+ homeostasis during myocardial contractility.

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.

P83 EFFICACY AND SAFETY OF LEVOSIMENDAN IN AN ISCHEMIC CARDIOGENIC SHOCK POPULATION: A 10–YEARS SINGLE CENTRE RETROSPECTIVE STUDY

Abstract Background Levosimendan is a Ca2+–sensitizer with inodilator action able to improve cardiac contractility without increse oxygen demand. In AHF setting clinical trial and registries showed an improvement in systemic haemodynamics without a decrease in in–hospital mortality. Purpose: evaluate safety and efficacy of Levosimendan in an ischemic CS population. Methods All consecutive patients with CS after AMI admitted at our CICU from March 2012 to July 2021 were included in this single–centre retrospective study. 39 patients received Levosimendan alone or in combination with other inotropic drugs. All patients had an invasive monitoring of arterial pressure and continuous ECG–monitoring. Patients with severe renal failure were excluded. An echocardiogram was performed before drug infusion and 3 days after. We collected data from haemodynamics and from ECG monitoring looking for arrhythmic events. Results We enrolled 167 patients with CS after AMI, 39 patients received Levosimendan and 10 of them required association with low–dosage noradrenaline. 32 received Levosimendan at dosage of 0,1 mcg/kg/min. The drug was started on average 4 days after hospitalization. Statistical analysis showed a significant change in left ventricular EF assessed by echocardiogram from 25% to 31% (P = 0.018, fig 1). We observed also an improvement of symptoms with an overall relief of dyspnea and fatigue clinically evaluated. The ECG monitoring showed ventricular arrhythmias (VA) in 11 patients (NSVT, SVT, VF) but the most frequent arrhythmia after Levosimendan was atrial fibrillation (AF) which was significantly associated with in–hospital mortality (OR = 1,82, p = 0,002), whereas VA did not. Moreover patients with new onset AF after Levosimendan showed a lower clinical and instrumental response to the drug. No significant changes in electrolytes (sodium and potassium) have been documented during arrhythmic events. Conclusion Levosimendan is useful in CS after AMI setting because has demonstrated to improve systemic hemodynamics parameters and symptomatology. Overall Levosimendan is safe with a low rate of ventricular arrhythmias that, in our sample, are not associated with in–hospital mortality. Moreover we observed also a significant increase in AF that was associated with in–hospital mortality, but further studies in larger populations could be advisable to describe the real incidence of AF after Levosimendan infusion and its prognostic role in CS patients.

Efficacy of levosimendan infusion in patients undergoing a left ventricular assist device implant in a propensity score matched analysis of the EUROMACS registry-the Euro LEVO-LVAD study.

Early right-sided heart failure (RHF) was seen in 22% of recipients of a left ventricular assist device (LVAD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). However, the optimal treatment of post-LVAD RHF is not well known. Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure. We sought to evaluate the efficacy of levosimendan on post-LVAD RHF and 30-day and 1-year mortality. The EUROMACS Registry was used to identify adults with mainstream continuous-flow LVAD implants who were treated with preoperative levosimendan compared to a propensity matched control cohort. In total, 3661 patients received mainstream LVAD, of which 399 (11%) were treated with levosimendan pre-LVAD. Patients given levosimendan had a higher EUROMACS RHF score [4 (2- 5.5) vs 2 (2- 4); P < 0.001], received more right ventricular assist devices (RVAD) [32 (8%) vs 178 (5.5%); P = 0.038] and stayed longer in the intensive care unit post-LVAD implant [19 (8-35) vs 11(5-25); P < 0.001]. Yet, there was no significant difference in the rate of RHF, 30-day, or 1-year mortality. Also, in the matched cohort (357 patients taking levosimendan compared to an average of 622 controls across 20 imputations), we found no evidence for a difference in postoperative severe RHF, RVAD implant rate, length of stay in the intensive care unit or 30-day and 1-year mortality. In this analysis of the EUROMACS registry, we found no evidence for an association between levosimendan and early RHF or death, albeit patients taking levosimendan had much higher risk profiles. For a definitive conclusion, a multicentre, randomized study is warranted.

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.

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.

Levosimendan Hemodynamic Effects Depending on the Outcome of Sepsis

The objective: to study hemodynamic and clinical effects of levosimendan depending on the clinical outcome in patients with sepsis and impaired cardiac pumping function.Subjects and Methods. the retrospective study involved 31 patients of 52.7 ± 2.8 years old with sepsis or septic shock which were treated with levosimendan at the dose of 0.16 [0.15‒0.17] mg/kg (0.11 [0.1‒0.12] μg × kg-1 × min-1) on days 1–4 of ICU stay. The patients were divided into the following groups: Group 1 ‒ survivors (n = 19) and Group 2 – non-survivors (n = 12). Central hemodynamics was assessed through transpulmonary thermodilution. The differences were considered statistically significant at p &lt; 0.05.Results. Most of the hemodynamic parameters and vasopressors and inotropes doses had no differences between the groups before levosimendan administration. There were no differences in the cardiac index (3.8 ± 0.3 vs 3.5 ± 0.3 L/min/m2; p = 0.479) between the groups following levosimendan administration, however, Group 1 demonstrated the following parameters to be lower versus Group 2: central venous pressure (7 ± 0.7 vs 11 ± 1 mm Hg; p = 0.005), blood lactate (1 [0.9‒1.8] vs 2.4 [2.2‒3.3] mmol/L; p = 0.04), norepinephrine dosages (0.2 [0.15‒0.35] and 0.5 [0.4‒0.6] ng/kg/min; p = 0.023 ), global end-diastolic volume index (693 [688‒28] vs 870 [779‒961] mL/m2; p =0,0009) and the level of NT-proBNP (1,590 [1,080‒3,160] vs 35,000 [21,400‒35,000] pg/mL; p = 0,0001). Global heart ejection fraction (23 [21‒27] vs 15 [12‒20]%; p = 0.015) and heart function index (6 [5‒8] vs 3 [ 3-4] min-1; p = 0.003) ) were higher in Group 1 versus Group 2. APACHE II &gt;19 (AUC 0.906; p &lt; 0.0001), SOFA &gt; 9 (AUC 0.805; p = 0.0002); heart rate &gt; 114 min-1 (AUC 0.755; p = 0.0095), and index of total peripheral vascular resistance &lt; 1,700 dyn × s × cm-5 × m2 (AUC 0.806; p = 0.001) before levosimendan administration were the independent predictors of death in patients treated with levosimendan.Conclusion: non-survivors patients with sepsis had significantly higher APACHE II and SOFA scores, higher heart rate and lower index of total peripheral vascular resistance before levosimendan infusion. In survivors levosimendan infusion at a standard dose led to a significant improvement in the heart pumping function accompanying by global heart ejection fraction and heart function index increasing and NT-proBNP decreasing. In non-survivors such favorable central hemodynamics changes did not occur, although the cardiac index increased after inodilator administration. Further studies of levosimendan efficacy in patients with sepsis of varying severity are advisable. It is necessary to specify the indications and contraindications for levosimendan administration to patients with sepsis.

Inotrope and vasopressor use in cardiogenic shock: what, when and why?

Despite increasing interest in the management of cardiogenic shock (CS), mortality rates remain unacceptably high. The mainstay of supportive treatment includes vasopressors and inotropes. These medications are recommended in international guidelines and are widely used despite limited evidence supporting safety and efficacy in CS. The OptimaCC trial further supports that norepinephrine should continue to be the first-line vasopressor of choice in CS. The CAPITAL DOREMI trial found that milrinone is not superior to dobutamine in reducing morbidity and mortality in CS. Two studies currently underway will offer the first evidence of the necessity of inotrope therapy in placebo-controlled trials: CAPITAL DOREMI2 will randomize CS patients to inotrope or placebo in the initial resuscitation of shock to evaluate the efficacy of inotrope therapy and LevoHeartShock will examine the efficacy of levosimendan against placebo in early CS requiring vasopressor therapy. Review of the current literature fails to show significant mortality benefit with any specific vasopressor or inotropic in CS patients. The upcoming DOREMI 2 and levosimendan versus placebo trials will further tackle the question of inotrope necessity in CS. At this time, inotrope selection should be guided by physician experience, availability, cost, and most importantly, individual patients' response to therapy.

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.

Levosimendan and heart failure: A retrospective case series

Levosimendan is characterized with positive inotropic and vasodilatory effects that has beneficial effects on myocardial performance. The aim of our study was to describe the clinical, biological and echocardiographic efficacy of this molecule according to the experience of our cardiology department. This is a monocentric, retrospective, descriptive study about patients hospitalized in the cardiology department of Sahloul hospital between January and December 2019 and who received a Levosimendan treatment. Six levosimendan cures were administered to six patients. The average age was 49.6 ± 17 years. Three patients received an initial bolus followed by a 24-hour infusion. We did not report any side effects that led to discontinuation of treatment. Inotropic agents’withdrawal was possible in 3 of the 4 patients who were on inotropic support. Death occurred in one patient. After levosimendan infusion, mean diuresis increased from 0.63cc/kg/hour to 1.51cc/Kg/hour ( P = 0.007). The mean heart rate before the start of the treatment and 48 hours afterwards were 97 and 85.6bpm respectively ( P = 0.4). Mean Systolic blood pressure increased from 89 mmHg to 92 mmHg 48 hours after the start of the treatment ( P = 0.42). Biologically, mean lactatemia levels decreased from 5 mmol/L to 3.24 mmol/L by day 2 after levosimendan treatment. There was a significant improvement in mean left ventricule ejection fraction from 21.6% to 25.5% ( P = 0.05) after 48 hours. Systolic pulmonary arterial pressures decreased significantly after the same period from 64 mmHg to 50 mmHg ( P = 0.007). The mean value of S’ measured at the tricuspid annulus in tissue Doppler mode, increased from 7.6 cm/s to 8.8 cm/s on the second day of levosimendan treatment ( P = 0.03) Although our sample size was small, our results are consistent with the literature regarding the efficacy of Levosimendan in cardiogenic shock. Its high cost limits its use in our daily practice.

568 Echocardiography and impedance cardiography as determinants of successful slow Levosimendan infusion in patients with acute advanced heart failure

Abstract Aims Despite new therapeutic options, patients with heart failure (HF) still progress to advanced stage. Among new therapeutic options, Levosimendan was recently approved in order to treat patients hospitalized for acute decompensated heart failure (ADHF) with severe systolic dysfunction. The pharmacological effects of Levosimendan consist of inotropy, vasodilatation, and cardioprotection through the increase of calcium sensitivity. These effects should be monitored with echocardiography and in particular with speckle tracking and tri-dimensional echocardiography which appear to be useful in LV systolic function detection and monitoring. In this study we aim to evaluate the effect of slow infusion of Levosimendan on the non-invasive measurement of cardiac output, the speckle tracking parameters and the tri-dimensional echocardiography measurements in advanced ADHF patients. Methods and results This is a prospective observational study evaluating Levosimendan efficacy through advanced echocardiography. We enrolled 11 patients with diagnosis of ADHF who respect the recent ESC criteria of ‘advanced heart failure’. Patients underwent to blood sample examination to measure electrolytes, creatinine, and NTproBNP. Patients underwent to advanced echocardiography examination (performed for each patient pre- and post-Levosimendan infusion) with tri-dimensional echocardiography and global longitudinal strain assessment. Furthermore patients underwent to non-invasive cardiac output and cardiac index collection through impedance cardiography pre- and post-Levosimendan infusion. All patients were followed for 30 days after discharge for all cause of mortality and HF re-hospitalization. A total of 11 patients affected by advanced ADHF were included in this study. Mean age was 73.8 ± 4.7 years. 72.7% (n 8) patients were men. 81.9% (n 9) of patients recognize ischaemic heart disease as HF etiology. At admission mean systolic arterial pressure was 100 ± 17 mmHg, mean NTproBNP was 24 445 ± 12 194 pg/ml and mean serum creatinine was 1.55 ± 0.84 mg/dl. At tri-dimensional echocardiography mean LV ejection fraction (LVEF) was 19.7 ± 5.7% and at bi-dimensional echocardiography mean tricuspid anular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP) were, respectively, 12.5 ± 2.7 mm and 48 ± 16 mmHg. Mean LV global longitudinal strain (GLS) was −3.0 ± 1.8. Mean furosemide in-hospital infusion was 306 ± 102 mg/die and mean urine output 1436 ± 496 ml. None developed significant ventricular or supraventricular arrhythmias. All patients were treated with betablockers during infusion. At 30 days of follow-up two patients died and 1 patient was re-hospitalized. Evaluating the differences among our variables pre- and post-Levosimendan infusion, we found that NTproBNP was significantly reduced post-Levosimendan infusion (P = 0.01). Among ICG non-invasive measurement, we found significant differences in stroke volume (SV) and cardiac output (CO) in terms of significant improvement (P = 0.001 for both). Analysing tri-dimensional echocardiography variables, we observed a significant improvement of LVEF (P = 0.003), SV (P = 0.03) and 3-D LV GLS (P = 0.002). Furthermore, we observed a significant reduction in end-systolic volume (ESV) post-Levosimendan infusion (P = 0.02). Among bi-dimensional echocardiography measurements, there was a significant reduction in end-diastolic diameter of right ventricle (EDDRV) and in B-lines count (respectively, P = 0.02 and P = 0.002). Moreover, we observed a significant improvement in TAPSE (P = 0.003) and in LV GLS (P = 0.004). Conclusions Our study showed that slow Levosimendan infusion (12.5 mg at velocity of 0.05–1 mcg/kg/min) without bolus could be considered in advanced ADHF patients to improve cardiac performance without severe adverse events. ICG and echocardiography in-hospital evaluation seemed to be necessary to understand treatment success and patients status improvement as well as cardiac function benefit.

Efficacy of Levosimendan vs. Dobutamine in the Treatment of Ventricular Dysfunction in Patients Subjected to Aortic Valve Replacement

Introduction: The ischaemic lesion due to coarctation of the aorta, inadequate myocardial protection, cardioplegic solutions, hypothermia and other factors can contribute to alterations in the myocardial contractility in the postsurgical period of valve replacement. Objective: To determine the efficacy of Levosimendan vs. Dobutamine in the treatment of ventricular dysfunction in patients subjected to aortic valve replacement. Materials and Methods: Quasi-experimental research was carried out on 60 patients diagnosed with stenosis, insufficiency or double aortic lesion subjected to aortic valve replacement under general anaesthesia. Cohorts were randomly assigned, group I (n=30) Dobutamine at 7.5 μg/kg/min, and group II (n=30) Levosimendan infusion of 0.2 μg/kg/min. The following criteria were monitored in both groups arterial tension, heart rate, oxygen saturation, and the hemodynamic variables with central venous catheter 7 Fr Arrow and Swan Ganz catheter 7Fr Edwards via internal jugular. For the statistical analysis, the variables were analysed using the student’s t-test P&lt;0.05. Results: The average age was 57.02±13 years. The average dose was 3-5 gammas for Dobutamine and 0.1-0.2 gammas for Levosimendan. The left ventricular ejection fractions were 56.2±11% and 56.4±10%, respectively. In the postsurgical setting, significant differences were observed only in the capillary pressure (17.03±5.8 vs. 13.87±2.9 cmH2O, p&lt;0.01). The Levosimendan group (64.1±13.6 vs. 57.6±12.9%, p=0.06). Conclusion: The administration of Levosimendan during the perioperative aortic valve replacement was associated with a tendency of deterioration of the ejection fraction in the left ventricle compared to the use of Dobutamine.

Clinical efficacy of levosimendan vs milrinone in preventing low cardiac output syndrome following pediatric cardiac surgery.

Background:Prophylactic milrinone is commonly used to prevent Low Cardiac Output Syndrome (LCOS) after pediatric cardiac surgery. This study compares the use of levosimendan with milrinone when used as the primary inotrope following pediatric cardiac surgery.Subjects and Methods:Forty infants undergoing corrective surgery for congenital heart disease were recruited during the study and randomized into two groups (group L and group M). During rewarming, a loading dose of levosimendan or milrinone was administered followed by a 24-hour infusion of the chosen inotrope. Echocardiographic variables were measured postoperatively. Statistical analysis was done with SPSS-20 computer package. Association between the variables was found by independent t test. P < 0.05 was considered statistically significant.Results:Mean age and weight of the patient in Group L was 8.55 ± 5.83 months and 6.05 ± 2.09 kgs, while that in group M was 6.85 ± 3.57 months and 5.26 ± 2.11 kgs. 4 patients (20%) treated with levosimendan had LCOS in comparison with 6 (30%) patients in those treated with milrinone. Echocardiographic parameters in both groups L and M were comparable (cardiac index 3.47 ± 0.76 vs 3.72 ± 1.05 L/min/m2, EF 66.10 ± 7.82% vs 59.34 ± 10.74%, stroke volume index 25.4 ± 6.3 vs 27.74 ± 10.35 mL/m2). The duration of ventilation, ICU stay and hospital stay were lesser in group L (12.75 ± 9.69, 35.95 ± 12.11, 119.10 ± 46.397 vs 23.60 ± 22.03, 51.20 ± 29.92, 140.20 ± 52.65 hours).Conclusions:The incidence of LCOS was lesser in those patients treated with levosimendan, when compared with those treated with milrinone. Cardiac index and stroke volume index were comparable between the two groups. Thus, levosimendan provides a non-inferior alternative to milrinone when used as the primary inotrope following pediatric cardiac surgery.

Застосування левосимендану порівняно з добутаміном за необхідності інотропної підтримки в пацієнтів з гострою декомпенсованою хронічною серцевою недостатністю тяжкого ступеня

The aim – to conduct clinical effectiveness, meta-analysis of 30 and 120-days mortality data, pharmacoeconomic evaluation of levosimendan treatment compared with dobutamine in patients with severe acute decompensated chronic heart failure (ADCHF) who require inotropic support.Materials and methods. The PubMed and Cochrane databases were searched for direct randomized clinical trials of levosimendan treatment compared with dobutamine in patients with ADCHF. The clinical efficacy of levosimendan and dobutamine was analyzed. Pharmacoeconomic analysis was carried out using the cost-effectiveness method with an assessment of the incremental cost-effectiveness ratio. A decision tree model of levosimendan or dobutamine treatments was constructed. The efficacy endpoints and impact on the budget were analyzed in terms of long-term effectiveness of levosimendan and dobutamine use. Discounted was conducted with rate of 3 %. Sensitivity analysis was carried out in terms of price changing of drugs, the cost of drugs in mg, the likelihood of re-hospitalization of the patient in a 3-year horizon and survival in the long term.Results and discussion. Analysis of clinical data and meta-analysis of randomized clinical trials found that mortality rates with levosimendan and dobutamine in the 30-day period were 9.6 % and 13.8 %, RR 0.71 (95 % CI 0.53–0.95) and in the 120-day period – 13.5 % and 25.2 %, RR 0.54 (95 % CI 0.32–0.92), respectively. The total cost of the course of treatment, taking into account the price of the drug, medical devices, staff services, diagnostic procedures and treatment of adverse reactions when using levosimendan, was 34 003.02 UAH per patient and 18 787.28 UAH when treated with dobutamine. The weighted average hospital stay was 6.4 days in case of levosimendan treatment and 7.5 days of dobutamine treatment. Extrapolation of the data from clinical trials to the 3-year survival rate of patients allowed us to determine an additional indicator of efficacy – the number of life years saved with levosimendan – 2.64 and 2.37 with dobutamine treatment. A cost-effectiveness analysis found that levosimendan is more efficient but more expensive technology compare to dobutamine. The incremental cost-effectiveness ratio for the additional life year saved of a patient with severe CHF is 43,473.55 UAH, which is 6 times less than the likely threshold of willingness to pay in Ukraine.Conclusions. The multivariate sensitivity analysis detected the model sustainability to the most crucial parameters of the model – drug price; the cost of drugs associated with their actual use in mg, the possibility of re-hospitalization of the patient in a 3-year horizon, and long-term survival, which is associated with the time horizon of the model. The total cost of a cohort of patients with ADCHF in Ukraine when using scenario 1 (100 % distribution of costs for dobutamine treatment) over 5 years is 268 188 351.94 UAH, when using scenario 2 (100 % distribution for treatment with levosimendan) total budget costs will be in amount of 485 393 073.09 UAH, if scenario 3 is applied (gradual 5 % transition in the treatment of patients with ADCHF with dobutamine for treatment with levosimendan within 5 years), the total budget costs will amount to 289 916 431.92 UAH.