Levosimendan Infusion Research Articles

Effects of repeated administration of Levosimendan in advanced heart failure in the elderly patient

Abstract Introduction Advanced heart failure (AHF) is characterized by repeated episodes of hemodynamic instability, frequent hospitalizations with progressive reduction in quality of life. The aim of the study was to verify in a small group of patients, no longer susceptible to heart transplantation (HT) and left ventricular assistance (LVAD), the effectiveness of monthly treatment with Levosimendan for a period of at least 6 months on quality of life and hospitalization. Materials and methods 29 elderly patients (≥65 years) with AHF, excluded from the waiting list for HT or no longer eligible for inclusion on the waiting list were enrolled. 12 patients practiced at least 1 infusion of Levosimendan and were considered as cases, while 17 patients with maximized treatment were used as controls. All patients underwent a multidimensional evaluation in which Fraity was assessed according to Fried criteria, cognitive function with Mini-Mental State Examination (MMSE), depressive symptoms with Geriatric Depression Scale (GDS). Results The 29 patients were followed up monthly and the 12 patients of Levosimendan group practiced an average of 4.6±2.7 infusions in absence of adverse events. The mean age was 73.3±6.2, 87.5% males, with a NYHA class of 3.4±0.4, an ejection fraction of 26.6±4.9 and NT-pro-BNP value of 7016.8±4876.1. Renal function was impaired with eGFR (ml / min) = 36.8±20.1. These patients had been hospitalized 1.8±0.7 times in the previous year. The data are not statistically different compared to the control group although a greater severity of the clinical condition of the case group is evident. The 6 minute walking test (6MWT) was 201.4±118.1 meters. The mean values of Frailty was 4.6±0.5, the GDS 6.4±4.2 and the MMSE 23.8±4.3. Only the MMSE was lower in the case group than in the controls (26.9±1.9, p=0.022). The results in terms of pre-post treatment difference identify an improvement of 35.3±136.3 meters at 6MWT in patients treated with Levosimendan compared to −72.2±94.2 meters in controls (p=0.030), Frailty is reduced by 1.4±1.6 points compared to 0.1±1.1 in controls (p=0.030), the GDS decreases by 0.9±1.5 in cases and increases by 2±2.1 in the control group (p=0.020), the MMSE score increases by 2.12±4.1 in treated patients, while it is reduced by 2.75±2.3 in the control group; p=0.003. The eGFR is reduced in both groups although more in the controls (−1.87±5.8 vs −10.8±11.1; p=0.043). There are no significant differences in mortality while there was less hospitalization during the follow-up period 0.9±0.6 vs 2.4±1.5; p=0.016). Multiple regression analysis shows that hospitalizations reduction is correlated with the recovery of frailty. This association is independent by age and disease severity. Conclusion Levosimendan improves physical and cognitive function, at the same time a minor decrease in renal function is observed, with a reduction of unscheduled visits to the hospital. Funding Acknowledgement Type of funding sources: None.

Efficacy of perioperative levosimendan on cardiac protection in patients undergoing coronary artery bypass surgery

These risks have led to the appearance of several ways to provide better outcomes. These ways are either mechanical like intraaortic balloon pump (IABP) or using medical inotropic drugs either adrenergic (epinephrine, norepinephrine &dobutamine) or non-adrenergic (levosimendan) drugs. It is indicated for the short-term treatment of acutelyPatients and MethodPatients had collected, withpoor left ventricular function ejection less than or equal to 40%. Cases had allocated into two gatherings of 50 cases.cases had admitted to the cardiovascular intensive care unit (ICU) 24h before surgery, a peri-operative dose of continuous levosimendan infusion cases will be submitted to conventional inotropes only (non levosimendan gathering) according to their medical requirements.Objective: to detect the outcome of clinical use of preioperative Levosemindan for cases undergoing coronary artery bypass grafting comparing it with the conventional medications as catecholamines.ResultsGathering A included 38 cases received levosimendan Gathering B included 40 cases received conventional cardiac support. A critical difference between both gatherings regarding total operative time, total bypass time, failure of weaning from cardiobypass (C.P.B), the use of intraoperative I.A.B.P.. There had a statistically critical difference between both gatherings in which C.V.P had lower in levosimendan .There had statistically critical difference regarding base critical in the levosimendan gathering. with high statistical difference for medical support, no difference for support .Conclusionthe use of levosimendan perioperative is useful than cathecholamins

B-PO02-024 ATP-SENSITIVE POTASSIUM CURRENT OPENER LEVOSIMENDAN MODULATES ACTION POTENTIAL DURATION ALTERNANS PROPERTIES AND PREVENTS VENTRICULAR ARRHYTHMIA DURING THERAPEUTIC HYPOTHERMIA

Therapeutic hypothermia (TH) increases the risk of ventricular arrhythmia (VA) by prolonging the action potential duration (APD) and enhancing the spatial discordant alternans (SDA) on APD. We hypothesized that levosimendan, an ATP-sensitive potassium current opener, might shorten the already prolonged APD, attenuate the SDA on APD, and prevent VA during TH. Langendorff-perfused isolated rabbit hearts were subjected to 15-min TH (30°C) followed by 30-min treatment with levosimendan (0.5 μM, n=9) or vehicle (n=8). Using an optical mapping system, APD was evaluated by S1 pacing. The threshold of SDA on APD was defined as the longest S1 pacing cycle length (PCL) at which SDA on APD was detected. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 s at the shortest PCL that achieved 1:1 ventricular capture. The APD was shortened from 259±8 ms at TH to 241±18 ms after levosimendan infusion at PCL of 400 ms (p=0.024). The threshold for SDA on APD was also shortened from 327±88 ms at TH to 311±68 ms after levosimendan infusion (p=0.003). The VF inducibility was decreased by levosimendan from 39±30% at TH to 14±12% with levosimendan (p=0.023). In control hearts, the APD, SDA threshold on APD (p=0.74), and VF inducibility (p=0.12) were not changed by vehicle during TH. Levosimendan might protect the hearts against VA during TH by shortening the APD and attenuate SDA on APD. Enhancing ATP-sensitive potassium current with levosimendan during TH might be a novel approach to prevent VA during TH.

The Preoperative Use of Levosimendan in Patients undergoing Coronary Artery Bypass Surgery with Low Ejection Fraction

Background: Levosimendan is a calcium sensitizer with positive inotropic, vasodilatory, and cardioprotective actions. Levosimendan infusion time may affect the outcomes. Our objective was to evaluate its efficacy and safety when used before coronary artery bypass grafting (CABG) in patients with low ejection fraction.
 Methods: This prospective observational study included 150 CABG patients with ejection fraction ≤ 40% divided into two groups. In the Levosimendan group (n= 75), it was given preoperatively, and in the conventional group (n= 75), myocardial support was used if indicated.
 Results: Operative time (344±28.7 vs. 421.4±34.5 min) and cardiopulmonary bypass time (97±17.4 vs. 127.4±24.5) were significantly shorter in the Levosimendan group (P˂ 0.001, for both). Failure to wean from bypass (13 (17.3%) vs. 23 (30.7%), P=0.06) and the need for intra-aortic balloon pump (6 (8%) vs. 14 (18.7%), P= 0.06) were non significantly lower in the Levosimendan group. The mechanical ventilation duration (12±3.3 vs. 19.6±4.7 h, P= 0.04) and ICU stay (3.8±1.2 vs. 5.3±1.4 days, P ˂ 0.001) were lower with levosimendan. Mortality was non-significantly lower in the Levosimendan group (10 (13.3%) vs. 18 (24%), P= 0.09). There were no differences in atrial and ventricular arrhythmias between groups.
 Conclusion: The preoperative use of levosimendan could improve the outcomes in patients undergoing CABG with low ejection fraction. Levosimendan complication profile was comparable to the conventional approach

Changes in Stressed Blood Volume with Levosimendan in Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction: Insights Regarding Mechanism of Action From the HELP Trial

Levosimendan is a K+-ATPase activator, cardiac myofilament Ca2+sensitizer, and phosphodiesterase inhibitor with positive inotropic effects and vasodilatory properties in the pulmonary and systemic circulation, all of which are potential therapeutic targets for patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).1 In the recent multicenter, double-blind, placebo-controlled Hemodynamic Evaluation of Levosimendan in Patients with HFpEF (HELP) study, a weekly infusion of levosimendan decreased the pulmonary capillary wedge pressure (PCWP) and central venous pressure, and was associated with a significant increase in 6-minute walk distance.

Effects of levosimendan on renal blood flow and glomerular filtration in patients with acute kidney injury after cardiac surgery: a double blind, randomized placebo-controlled study

BackgroundAcute kidney injury (AKI) is a common and serious complication after cardiac surgery, and current strategies aimed at treating AKI have proven ineffective. Levosimendan, an inodilatating agent, has been shown to increase renal blood flow and glomerular filtration rate in uncomplicated postoperative patients and in patients with the cardiorenal syndrome. We hypothesized that levosimendan through its specific effects on renal vasculature, a preferential vasodilating effect on preglomerular resistance vessels, could improve renal function in AKI-patients with who did not have clinical indication for inotropic support.MethodsIn this single-center, double-blind, randomized controlled study, adult patients with postoperative AKI within 2 days after cardiac surgery, who were hemodynamically stable with a central venous oxygen saturation (ScvO2) ≥ 60% without inotropic support were eligible for inclusion. After randomization, study drug infusions, levosimendan (n = 16) or placebo (n = 13) were given for 5 h. A bolus infusion of levosimendan (12 µg/kg), were given for 30 min followed by 0.1 µg/kg/min for 5 h. Renal blood flow and glomerular filtration rate were measured using infusion clearance of para-aminohippuric acid and a filtration marker, respectively. As a safety issue, norepinephrine was administered to maintain mean arterial pressure between 70–80 mmHg. Intra-group differences were tested by Mann–Whitney U-tests, and a linear mixed model was used to test time and group interaction.ResultsTwenty-nine patients completed the study. At inclusion, the mean serum creatinine was higher in the patients randomized to levosimendan (148 ± 29 vs 127 ± 22 µmol/L, p = 0.030), and the estimated GFR was lower (46 ± 12 vs 57 ± 11 ml/min/1.73 m2, p = 0.025). Levosimendan induced a significantly (p = 0.011) more pronounced increase in renal blood flow (15%) compared placebo (3%) and a more pronounced decrease in renal vascular resistance (− 18% vs. − 4%, respectively, p = 0.043). There was a trend for a minor increase in glomerular filtration rate with levosimendan (4.5%, p = 0.079), which did differ significantly from the placebo group (p = 0.440). The mean norepinephrine dose was increased by 82% in the levosimedan group and decreased by 29% in the placebo group (p = 0.012).ConclusionsIn hemodynamically stable patients with AKI after cardiac surgery, levosimendan increases renal blood flow through renal vasodilatation.Trial registrationNCT02531724, prospectly registered on 08/20/2015. https://clinicaltrials.gov/ct2/show/NCT02531724?cond=AKI&cntry=SE&age=1&draw=2&rank=1

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<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<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.

Predictors of diuresis response to levosimendan administration in patients with acute heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Levosimendan, a calcium sensitizer and potassium channel-opener, is appreciated for its effects on systemic and pulmonary hemodynamic and for the relief of symptoms in acute heart failure (AHF). Positive effects of levosimendan on renal function have been also described. The aim of the present analysis was to assess the predictors of the diuresis response to levosimendan administration in high risk acute heart failure patients. Methods We analysed 34 consecutive patients admitted with high risk AHF to one centre and treated in intensive cardiac care unit. Levosimendan was administered on top of other treatment as a 24-hour infusion of 12.5 mg total dose except for 7 patients (1 patient - terminated earlier due to intolerance, 5 patients – 48h infusion, 1 patient - 72h infusion). Decision of levosimendan administration was based on clinical status and left to attending physician. Diuresis and diuretic dosage before (24 hours) and after levosimendan infusion (48 hours) were taken into account for the present study. Results The AHF was primary of cardiac origin in all patients. In 6 (18%) it was due to recent acute myocardial infarction. In-hospital mortality was 24%. Median length of hospitalization was 26 days (range 6 to 107 days). Mean age of the patients was 66 ± 12 years, 25 (74%) were men. Mean INTERMACS score was 3.4 ± 1.4 with wet-cold clinical profile present in 13 (38%) of patients. Mean left ventricle ejection fraction (LVEF) was 27 ± 13%, mean NTproBNP was 17176 ± 12464 pg/ml, and mean eGFR 48 ± 22 ml/min/1.73m2. At the time of levosimendan administration patients had background treatment with catecholamines (mean number per patient 1.4 ± 1.1, range 0-3) and with diuretics (mean dosage of furosemide 167 ± 102 mg/24h, range 20-500). 48-hours diuresis after levosimendan administration varies from 950 to 11300 ml (mean 4307 ± 2418 ml). It was significantly lower in patients with cold-wet profile (2646 ± 1335 vs. 5335 ± 2381 ml in other clinical profiles, p = 0.0002). Additionally, 48-hour diuresis was negatively correlated with age (r=-0.46, p = 0.0062) and the number of background catecholamines (r=-0.47, p = 0.0047), and not significantly with the furosemide dosage (r=-0.28, p = 0.10) – figure. No association with diuresis was found for LVEF, NTproBNP, and eGFR. In multiple regression analysis (model R2 = 0.63, p = 0.0085) both older age (p = 0.026) and cold-wet profile (p = 0.0074) were significant predictors of poor diuresis after levosimendan administration. Conclusion Older age and cold-wet profile were significant predictors of poor diuresis response to levosimendan administration in high risk acute heart failure patients. Although concomitant catecholamines and high diuretic dosage use cloud also be markers of non-responders to levosimendan in terms of diuresis. Abstract Figure

Bolus-free low-dose levosimendan infusion for acute decompensated hypoperfused heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Aims and Methods Aim of this study was to assess the feasibility of a bolus-free, low-dose levosimendan infusion for acute decompensated heart failure (ADHF) with hypoperfusion. All consecutive patients who received levosimendan without intravenous bolus at our Department for ADHF in the last 6 months were included in this is a single-center retrospective study. To avoid abrupt drop in blood pressure, all patients started infusion at 0.01 mcg/kg/min, and gradual titration was achieved, up to 0.1 mcg/kg/min. Continuous variables are reported as medians (IQR), categorical as proportions. Paired measures were compared with the Wilcoxon signed-rank test. p-value was set at 5%. Analyses were performed using RStudio v1.3. Results We included 26 patients [males 84.6%; age 72 (59-76) years]. Patients had severe LV dysfunction [LVEF of 20 (20-25)%] and moderate/severe RV dysfunction in 46.2%. Most patients were admitted for cardiogenic shock (26.9%) or low-output state (61.5%); baseline serum lactate was 1.6 (1.2-3.2) mmol/L. Etiology was ACS in 26.9% patients, worsening HF in 53.8%, and valvular disease in 26.9%. All patients required inotropes: 73.1% required adrenaline [max dose 0.10 (0.05-0.15) mcg/kg/min]; 50.0% required noradrenaline [max dose 0.10 (0.05-0.18) mcg/kg/min]; 26.9% received levosimendan alone [max dose 0.05 (0.03-0.10) mcg/kg/min]. Levosimendan was used in combination with adrenaline in 69.2%, after 3 (0-4) days of adrenaline initiation. Duration of levosimendan infusion was 3 (1-4) days. MCS was pursued in 69.2% [57.7% IABP, 15.4% Impella CP, and 3.8% VA-ECMO]. Oro-tracheal intubation was required in 50.0%, CVVHDF was required in 11.5% patients. No patient required levosimendan interruption for hypotension/arrhythmia. In-hospital mortality was 7.7%. One patients underwent successful LVAD implantation, and one patient was referred for HTx. Invasive hemodynamic data, before and during levosimendan, was available for 7 patients. Initiation of levosimendan led to a non-significant drop in SVR [14.8 (13.3-16.9) vs 19.5 (14.6-25.4) WU; p = 0.093], but SBP was unchanged (p = 0.470). Left ventricular systolic performance was improved: CI [2.6 (2.4-2.7) vs 2.2 (2.0-2.3) Lt/min/m²; p = 0.016]; CPO [0.9 (0.8-1.0) vs 0.8 (0.8-0.9) W; p = 0.031]. Mean PAP (p = 0.297), and PCWP (p = 0.149) remained unchanged. Notably, no significant adjustments in diuretic (p = 0.422) or adrenaline (p = 0.999) doses, IABP counterpulsation ratio (p = 0.999), or Impella flow (p = 0.999) were recorded between these longitudinal assessments. As a result of improved myocardial function, LVEF increased from admission to discharge [20 (20-25) vs 25 (20-32)%; p = 0.024]. Discussion This preliminary study reports on a bolus-free, low-intensity levosimendan regimen for ADHF with hypoperfusion. Levosimendan improved indexes of myocardial performance. In this cohort, levosimendan often required concomitant inopressor and was started at a very low dose to avoid abrupt drop in blood pressure. Abstract Figure 1

Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial

ObjectivesThe purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). BackgroundThere are no proven effective treatments for patients with PH-HFpEF. MethodsPatients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 μg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1 ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages. ResultsThirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (−1.4 mm Hg; 95% confidence interval [CI]: −7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (−3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo. ConclusionsSix weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF [HELP]; NCT03541603)

Intermittent Levosimendan Infusion in Ambulatory Patients with End-Stage Heart Failure: A Systematic Review and Meta-Analysis

Purpose The safety and efficacy of ambulatory intermittent LEVO infusions in patients with end-stage HF are yet not established. We sought to synthesize the available evidence regarding safety and efficacy of intermittent Levosimendan (LEVO) infusions in ambulatory patients with end-stage heart failure (HF). Methods We systematically searched MEDLINE, EMBASE, SCOPUS, Web of Science and Cochrane databases, from inception to September 27,2019 for studies reporting outcome of adult ambulatory patients with end-stage HF treated with intermittent LEVO infusion. Results Fifteen studies (8 randomized and 7 observational), comprised 984 patients (LEVO[N=727] and controls[N=257]) met the inclusion criteria. LEVO was associated with improved New York Heart Association(NYHA) functional class, (weighted mean difference [WMD] -1.04, 95%CI -1.70 to -0.38, p Conclusion Intermittent Levosimendan infusions in ambulatory patients with end-stage HF is associated with less frequent cardiovascular death alongside with improved NYHA class, quality of life, BNP levels and LV function. However, the current evidence is limited by heterogeneous and relatively small studies.

The direct comparison of inhaled versus intravenous levosimendan in children with pulmonary hypertension undergoing on-cardiopulmonary bypass cardiac surgery: A randomized, controlled, non-inferiority study

Study objectivePulmonary arterial hypertension is commonly seen in children with left to right intracardiac shunts and affects the outcomes of cardiac surgery. Our study aimed to compare the efficacy of inhaled levosimendan (LS) versus intravenous LS in reducing elevated pulmonary artery pressure (PAP) in children scheduled for cardiac surgery. DesignNon-inferiority, prospective, randomized, blinded, controlled study. SettingOperative room and intensive care unit (ICU), institutional children's hospital of Mansoura Faculty of Medicine, Egypt. Patients50 patients of either sex, aged 1 to 5 years undergoing surgical repair of intracardiac left to right shunt complicated by pulmonary hypertension were recruited for the study. InterventionsIn the intravenous LS group, patients received intravenous infusion of LS a rate of 0.1 μg/kg/min and in the inhaled LS group, LS (36 μg/kg/6 h) was delivered by nebulization. MeasurementsThe primary endpoint was systolic PAP, while the secondary endpoints were the heart rate, mean arterial blood pressure, dose of norepinephrine, time to extubation and ICU length of stay. Main resultsBoth intravenous and inhaled routes of LS similarly reduced the high systolic PAP over all time points of measurement and intravenous LS was associated with higher heart rate, lower arterial pressure and the need for a higher dose of norepinephrine than the inhaled LS. ConclusionInhalation of LS is non-inferior to intravenous LS in reducing high PAP in children who underwent on-pump cardiac surgery and it is associated with less tachycardia and hypotension with reduced need for vasoactive drugs.

P0349 / #1859: CORRELATION OF THE EFFICIENCY OF LEVOSIMENDAN BY MRI IN CARDIAC FIBROSIS PATIENTS

Aims & Objectives: Our aim is to evaluate the responses of patients with cardiac fibrosis to levosimendan infusion. Methods: Patients with end-stage heart failure and receiving levosimendan infusion were detected. The Magnetic Resonance Image(MRI) results were evaluated. The responses of those with fibrosis to levosimendan infusion were examined. Results: Between 2012 and 2020, a total of 98 patients were given infusion of levosimendan 138 times. Some patients received recurrent infusions. The most common diagnosis was dilated cardiomyopathy. In addition, there were conditions such as septic shock, congenital heart anomalies, myocarditis, and cardiac dysfunction. A total of 25 patients (25,5%) became ex. Heart transplantation was performed in 4(4%) patients. Cardiac Magnetic Resonance Image(MRI) was performed in 12 (12,2%) patients in total. Our aim was to determine the effectiveness of levosimendan in the presence of cardiac fibrosis. There was no fibrosis in 2 (16%) patients and was fibrosis in 10 patients(84%). Only 1 of 10 patients(10%) with fibrosis was ex. Although 9 other patients (75%) had cardiac fibrosis, they benefited from levosimendan infusion. They are waiting for recovery or heart transplantation. Conclusions: Levosimendan is a calcium sensitizing pharmacologic agent, performs peripheral, pulmonary and systemic vasodilation and it increases myocardial activity and cardiac output. We think that levosimendan infusion is an effective treatment option in cases that cause severe cardiac dysfunction. Although cardiac fibrosis is present in patients, levosimendan can be used as an effective rescuer treatment method.

LEVOSEMINDAN VERSUS INTRA-AORTIC BALLOON PUMP IN LOW EJECTION FRACTION CABG PATIENTS

Background: Preoperative left ventricular dysfunction is an independent risk factor for perioperative mortality and morbidity and is also associated with postoperative low cardiac output syndrome. IABP improved outcomes in high-risk cardiac patients. However, installation of the balloon has many disadvantages. Recently, a new drug named Levosimendan is commonly used as an inotropic support. it does not increase oxygen demand of myocardium.Aim of the work: The purpose of our study was to compare the efficiency of levosimendan versus intra-aortic balloon pump in patients with poor left ventricular function undergoing coronary artery bypass grafting (CABG) with ejection fraction less than 35%.Patients and Methods: sixty patients were randomized into 2 groups, according to the treatment they received - either levosimendan (Group A) or intra-aortic balloon counter pulsation (Group B). and compared with respect to The use of inotropic drugs, weaning from CPB, Hemodynamics, transfusion requirements, ICU stay, hospital stay and in-hospital mortality.Results: There were no differences in preoperative characteristics including patients’ age, sex, BMI, and comorbidities. The Levosemindan group had reduced transfusion requirements and shorter ICU stay as compared to IABP group.Conclusion: levosimendan infusion after induction of anesthesia is a good choice with an acceptable option in comparison to IABP. The use of levosimendan in high-risk cardiac patients is comparable to IABP in improving hemodynamics during and after conventional on-pump CABG and results in a shorter ICU stay.

P0261 / #2147: MANAGEMENT OF DRUG REFRACTORY ARRHYTHMIA TREATED WITH EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) SECONDARY TO COVID-19 INFECTION

AIMS & OBJECTIVES: Myocarditis caused by SARSCoV2 is one of the causes of death in this pandemic, mainly due to arrhythmias, leading to heart failure and cardiogenic shock. The use of ECMO is one strategy as a bridge to treatment. Our objective is to describe the case of a patient with arrhythmias secondary to COVID-19 and the strategies used. METHODS: Fourteen years old male started with a retrosternal burning pain, palpitations and dyspnea, was admitted to the emergency department. An electrocardiographic trace was taken showing ventricular tachycardia with hemodynamic compromise, synchronized cardioversion was performed. Management with amiodarone, metoprolol and lidocaine is added. It was decided to enter therapeutic catheterization for ablation. Due to refractoriness to treatment, it is left with infusion of amiodarone, lidocaine and esmolol. Evolves into cardiogenic shock, requiring aminergic management with epinephrine, vasopressin, milrinone and levosimendan infusion. RESULTS: It was decided to start with extracorporeal membrane support as a management for arrhythmia refractory to pharmacological treatment. Required for 80 hours. Myocarditis is suspected, and PCR test for SARS-CoV2 is requested, which is obtained as positive. Continuing with the presence of rhythm alterations when attempting to withdraw drug management, it was decided to enter the hemodynamic room to perform ablation again, which was performed successfully. CONCLUSIONS: Arrhythmias secondary to COVID-19 have been described in adult patients. However, the manifestations of this infection in pediatric patients differ in several aspects, so it is important to study this pathology as a probable manifestation of great impact on the survival of the pediatric patient.

P0760 / #2144: MANAGEMENT OF DRUG REFRACTORY ARRHYTHMIA TREATED WITH EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) SECONDARY TO COVID-19 INFECTION

Aims & Objectives: Myocarditis caused by SARS-CoV2 is one of the causes of death in this pandemic, mainly due to arrhythmias that it causes, leading to heart failure and cardiogenic shock. The use of ECMO for the treatment of these rhythm abnormalities is one strategy as a bridge to treatment. Our objective is to describe the case of a patient with arrhythmias secondary to COVID-19 and the strategies used. Methods: Fourteen years old male started with a retro-sternal burning pain, palpitations and dyspnea, was admitted to the emergency department. An electrocardiographic trace was taken showing ventricular tachycardia with hemodynamic compromise, synchronized cardioversion was performed. Management with amiodarone, metroprolol and lidocaine is added. It was decided to enter therapeutic catheterization for ablation. . Evolves into cardiogenic shock, requiring aminergic management with epinephrine, vasopressin, later with infusion of milrinone and levosimendan. Results: Started with extracorporeal membrane support as a management. Required for 80 hours. Myocarditis is suspected, and PCR test for SARS-CoV2 is requested, which is obtained as positive Continuing with the presence of rhythm alterations when attempting to withdraw drug management, it was decided to enter the hemodynamic room to perform ablation again, which was performed successfully. Conclusions: Arrhythmias secondary to COVID-19 have been described in adult patients. However, the manifestations of this infection in pediatric patients differ in several aspects, so it is important to study this pathology as a probable manifestation of great impact on the survival of the pediatric patient.

P0357 / #2134: LEVOSIMENDAN RESCUE TREATMENT FOR REFRACTORY CARDIOGENIC SHOCK IN CHILDREN

Aims & Objectives: Levosimendan, a calcium-sensitizing vasodilator agent, is being used frequently in pediatric acute heart failure, especially in postcardiac surgery. We report here, our single center experience in 4 children with refractory acute cardiogenic shock due to myoacarditis and dilated cardiomyopathy with a focus on the safety and efficiency of the drug. Methods: Retrospective review of 3 pediatric cases, 3, 5 and 10 years old, presented with cardiogenic shock due to acute myocarditis in 2 cases and to dilated cardiomyopathy decompensation in one case. Crdiogenic Shock was refractory to classic support with epinephrine and milrinone. Results: The treatment with classic intravenous inotropic agents (epinephrine and milrinone) was failing with clinical deterioration. Before starting Levosimendan infusion, there was severe left ventricular dilatation (end-diastolic diameter z-score 3,1; 4.3 and 5,3) and reduced myocardial contractility with ejection fraction (EF - 21%, 28%, 27%) and fractional shortening (FS - 17%, 19%, 20%). Levosimendan rescue treatment was started with a continuous 24-h infusion (0.04-0,1 microg/kg/min). Both clinical, biological and echocardiography improvement was recorded: EF (52%, 49%, 57%), FS (24%, 29%, 37%) with normalization of lactate levels in the next 48 hours. Transient hypotension due to vasodilation and requiring a low dose of norepinephrine was seen in one patient. all Patients were weaned frome mechanical ventilation, inotropic support after 4, 5 and 7 days respectively and discharged alive. Conclusions: Ourexperience demonstrates that the use of levosimendan in childrens with refractory to classic inotropic support cardiogenic shock might result in a significant clinical and hemodynamic improvement and can be a safelife saving therapy.

Effect of levosimendan on long-term prognosis in patients with myocardial infarction and concomitant chronic brain ischemia

Aim . To study the effect of levosimendan (LS) on 1-year prognosis in patients with myocardial infarction (MI), complicated with heart failure (HF), and concomitant chronic brain ischemia (CBI). Material and methods . The study included 182 patients with Q-wave MI, complicated by HF with left ventricular ejection fraction (LVEF)<40%, and concomitant CBI (149 (81,9%) men and 33 (18,1%) women). The median age was 60,4 (53; 69) years. Group I (control) included 49 patients who received standard therapy; group II (experimental) — 133 patients who were injected with LS on days 1-2 of MI. All patients underwent echocardiography, duplex ultrasound of peripheral arteries and were examined by angioneurologist. A year later, the hard endpoints of recurrent MI, angina progression, revascularization, acute decompensated HF, rehospitalizations, strokes, and death were assessed. Results . According to multivariate regression analysis, LS administered in the acute period of myocardial infarction reduced the risk of hard endpoints (hazard ratio, 0,32,95% confidence interval, 0,2-0,52, p=0,001), but did not affect patient survival. Conclusion . In patients with MI complicated by left ventricular failure and associated with CBI, LS infusion in the acute period of MI can reduce the risk of adverse cardiovascular events during the year.

Intermittent outpatient administration of levosimendan improves right ventricular-pulmonary arterial coupling in ambulatory patients with advanced heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Intermittent infusions of levosimendan in an outpatient setting have been associated with improved symptoms and reduced hospitalizations in patients with advanced heart failure (HF). Little is known on the potential effect of intermittent levosimendan infusions on right ventricle (RV)-pulmonary arterial (PA) coupling in ambulatory patients with advanced HF. Purpose Aim of the present study was to explore the effects of intermittent levosimendan infusions on the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PAPs), an echocardiographic measure of RV/PA coupling, in ambulatory patients with advanced HF, and on left ventricular arterial coupling (VAC), expressed as the relationship between arterial elastance (Ea) and ventricular elastance (Ees). Methods 17 ambulatory patients with advanced HF treated with intermittent levosimendan (6-hour intravenous infusion, 0.2 ug/kg/min without bolus) received baseline clinical, biochemical and echocardiographic evaluation and changes in TAPSE/PAPs ratio were assessed from baseline to 48 hours after the infusion, based on the pharmacokinetic profile of levosimendan. VAC, expressed as Ea/Ees ratio, was obtained by a calculator (iElastance) designed for non-invasive single beat measure of end-systolic Ees and Ea according to Chen"s method. Results After 48 hours from levosimendan infusion, there was a significant improvement of TAPSE/PAPs ratio (p = 0.04), stroke voume (SV) (p = 0.05) and cardiac output (CO)(p = 0.04). We observed a significant reduction of Ea (p = 0.007) and of Ees (p = 0.01) and a non significant improvement of VAC (p = 0.4)(Tab.1). Conclusion. Our results show that an intermittent 6-hour levosimendan infusion at 0.2 ug/kg/min improves after 48 hours RV-PA coupling, SV, CO, Ea and Ees in ambulatory patients with advanced HF. Further studies including more patients are necessary to confirm these preliminary findings. Tab.1 Baseline 48h afterlevosimendan infusion p value NT-proBNP (pg/mL) 5607 ± 4300 3868 ± 3856 &amp;lt;0.001 LVEF (%) 24.1 ± 7.7 25.7 ± 7.3 0.5 SV (mL) 36.8 ± 12.4 46.1 ± 14.8 0.05 CO (L/min)36.8 ± 12.4 2.6 ± 0.7 3.2 ± 0.9 0.05 TAPSE/PAPs (mm/mmHg) 0.38 ± 0.13 0.49 ± 0.16 0.04 Ea (mmHg/mL/m2) 2.9 ± 0.9 2.1 ± 0.6 0.007 Ees (mmHg/mL/m2) 1.3 ± 0.4 1.0 ± 0.2 0.01 VAC 2.2 ± 0.6 2.0 ± 0.4 0.4

Effect of Preoperative Infusion of Levosimendan on Biomarkers of Myocardial Injury and Haemodynamics After Paediatric Cardiac Surgery: A Randomised Controlled Trial.

ObjectiveThe aim was to test the hypothesis that preoperative infusion of levosimendan would decrease patients’ cardiac biomarker profiles during the immediate postoperative stage (troponin I and B-type natriuretic peptide levels) more efficiently than placebo after cardiopulmonary bypass.MethodsIn a randomised, placebo-controlled, double-blinded study, 30 paediatric patients were scheduled for congenital heart disease surgery. 15 patients (50%) received prophylactic levosimendan and 15 patients (50%) received placebo from 12 h before cardiopulmonary bypass to 24 h after surgery.ResultsTroponin I levels were higher in the placebo group at 0, 12, and 24 h after cardiopulmonary bypass, although the mean differences between the study groups and the 95% confidence intervals (CIs) for troponin I levels did not present statistically significant differences at any of the three time points considered (mean differences [95% CIs] − 3.32 pg/ml [− 19.34 to 12.70], − 2.42 pg/ml [− 19.78 to 13.95], and − 79.94 pg/ml [− 266.99 to 16.39] at 0, 12, and 24 h, respectively). A similar lack of statistically significant difference was observed for B-type natriuretic peptide (mean differences [95% CIs] 36.86 pg/dl [− 134.16 to 225.64], − 350.79 pg/dl [− 1459.67 to 557.45], and − 310.35 pg/dl [− 1505.76 to 509.82]). Lactic acid levels were significantly lower with levosimendan; the mean differences between the study groups and the 95% CIs for lactate levels present statistically significant differences at 0 h (− 1.52 mmol/l [− 3.19 to − 0.25]) and 12 h (− 1.20 mmol/l [− 2.53 to − 0.10]) after cardiopulmonary bypass. Oxygen delivery (DO2) was significantly higher at 12 h and 24 h after surgery (mean difference [95% CI] 627.70 ml/min/m2 [122.34–1162.67] and 832.35 ml/min/m2 [58.15 to 1651.38], respectively).ConclusionsLevosimendan does not significantly improve patients’ postoperative troponin I and B-type natriuretic peptide profiles during the immediate postoperative stage in comparison with placebo, although both were numerically higher with placebo. Levosimendan, however, significantly reduced lactic acid levels and improved patients’ DO2 profiles. These results highlight the importance of this new drug and its possible benefit with regard to myocardial injury; however, evaluation in larger, adequately powered trials is needed to determine the efficacy of levosimendan.Trial registry number: EudraCT 2012-005310-19.