Levosimendan Therapy Research Articles

Vasoactive Management of Pulmonary Hypertension and Ventricular Dysfunction in Neonates Following Complicated Monochorionic Twin Pregnancies: A Single-Center Experience.

Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates. In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children's Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B). The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 (p = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, p = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 (p = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive-inotropic score (LVISmax) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], p = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], p = 0.011). Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants.

The Impact of Positive Inotropic Therapy on Hemodynamics and Organ Function in Acute Heart Failure: A Differentiated View.

Little is known about the impact of treatment with inotropic drugs on the interaction of hemodynamics, biomarkers, and end-organ function in patients with acute decompensated heart failure (HF) of different origins and heart rhythms. Fifty patients with different causes of acute decompensated HF (dilated cardiomyopathy DCM, ischemic cardiomyopathy ICM, atrial fibrillation AF, sinus rhythm/pacemaker lead rhythm SR/PM) were treated with dobutamine or levosimendan. Non-invasive hemodynamics, biomarkers, and parameters of renal organ function were evaluated at hospital admission and after myocardial recompensation (day 5 to 7). Twenty-seven patients with ICM and twenty-three patients with DCM were included. Thirty-nine patients were treated with dobutamine and eleven with levosimendan. Sixteen were accompanied by persistent AF and thirty-four presented either with SR or PM. In the overall cohort, body weight and biomarkers (NT-proBNP/ST2) significantly decreased. GFR significantly increased during therapy with either dobutamine or levosimendan. However, hemodynamic parameters seem to be only improved in patients with DCM, in the levosimendan sub-group, and in patients with SR/PM. Patients with acute decompensated HF benefit from positive inotropic therapy during short-term follow-ups. In particular, patients with DCM, those after levosimendan therapy and those with SR/PM, seem to benefit most from inotropic therapy.

Myocardial work index and myofilament calcium sensitivity: possible hand in hand markers of contractility in aortic valve stenosis patients - a translational study

Abstract Background In aortic valve stenosis, conventional echocardiographic parameters, such as ejection fraction (EF), are heavily influenced by the increased afterload caused by the valvular disease. Myocardial work index (GWI) quantifies myocardial deformation depending on the momentary LV pressure, potentially serving as a marker of LV contractility independent of loading conditions. Similarly, myofilament Ca2+ sensitivity (pCa50) followed the alterations of LV contractility in a rat model of pressure overload-induced heart failure. Therefore, GWI and pCa50 may also show correlation, as both can be reliable measures of contractility in diseases of chronically elevated LV afterload. Purpose Accordingly, our first aim was to assess the association of pCa50 and GWI in a rat model of pressure overload-induced heart failure and sham operated animals. We also aimed to evaluate the changes in GWI after myocardial Ca2+ sensitizing with levosimendan in aortic valve stenosis patients. Methods Firstly, on the thoracic aortic banded (n=2) and sham operated (n=3) rats speckle-tracking echocardiography and invasive LV pressure measurements were performed to calculate GWI. Using single permeabilized cardiomyocytes, pCa50 was calculated by myofilament force measurement. Secondly, to test our hypothesis in a clinical setting, 23 severe aortic valve stenosis patients (age 76±9 years, 39% female) were enrolled who received levosimendan therapy. Conventional and advanced echocardiographic measurements were performed before and after a 24-hour intravenous loading dose. We determined global longitudinal strain by speckle-tracking echocardiography, then using LV pressure curves estimated from systolic blood pressure and mean transaortic gradient, we quantified non-invasive global myocardial work index (GWI). Results In the animal study, GWI and pCa50 strongly correlated in the rats (r=0.942; p=0.017). In the clinical study, patients with a baseline EF <35% (n=12) had significantly increased GWI after the levosimendan therapy (533±347 vs. 660±419 mmHg%; p=0.004), while those who initially had an EF >35% (n=11) did not show any change (998±342 vs. 1003±275 mmHg%; p= 0.788). Also, the pre-levosimendan GWI showed a strong inverse correlation with the relative GWI change after the loading dose (r=-0.708; p=0.003). Conclusions We showed in an experimental setting, that GWI and pCa50 correlated in a rat model of pressure overload-induced heart failure and in sham operated controls. In the clinical setting, patients with severely decreased baseline EF and GWI benefited more from the Ca2+ sensitizing therapy, having better LV function after it, while those with better baseline function did not show improvement. Therefore, patients with worse baseline GWI initially might have had decreased Ca2+ sensitivity, which implies a possible correlation between GWI and pCa50 in patients with aortic valve stenosis, resembling the experimental findings.Correlation of pCa50 - GWICorrelation of GWI - relative GWI change

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.

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>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.

P240 PREOPERATIVE OPTIMISATION FOR A PATIENT WITH HEART FAILURE UNDERGOING MAJOR NON–CARDIAC SURGERY: AN EXAMPLE OF COLLABORATION BETWEEN THE MULTIMODAL PREHABILITATION CENTRE AND THE HEART FAILURE CLINIC AT CAREGGI UNIVERSITY HOSPITAL

Abstract Introduction Heart failure (HF) is a risk factor for postoperative mortality in major non–cardiac surgery. Collaboration between the Multimodal Preoperative Prehabilitation unit (MPP) and Heart Failure Clinic (HFC) could allow optimization of heart failure therapy and negative prognostic factors such as reduced functional capacity (FC), malnutrition, and sarcopenia to improve the prognosis of these patients. Case report: Mrs. C.M. is a 58–year–old patient who presents to the MPP unit in anticipation of total colectomy for drug–refractory ulcerative colitis. Mrs. C.M. has a past medical history significant for heart failure with reduced ejection fraction (EF 25%) of presumably valvular–arrhythmic etiology. She underwent tricuspid annuloplasty and mitral replacement surgery some years ago and is affected by atrial fibrillation. At the MPP unit, Mrs. C.M. had a reduced FC and was malnourished and sarcopenic. Blood tests showed iron deficiency anemia. Heart failure therapy (NYHA II) was not optimized according to guidelines. Therefore, the patient started multimodal prehabilitation consisting of aerobic and resistance exercise, nutritional intervention, intravenous iron infusion, and optimization of HF therapy. After the patient was evaluated at the HFC, she started empagliflozin, sacubitril/valsartan, and ranolazine; intermittent levosimendan therapy was also performed. She also underwent cardiac NMR, which showed non–ischemic fibrosis, and coronary angiography, which was negative. Finally, she underwent PM–ICD implantation. After six months of multimodal prehabilitation, there was an increase in EF (38% vs. 25%), a reduction in NT–proBNP (700 vs 4988 pg/mL), and mitigation of HF symptoms. There was also a marked improvement in FC (383 vs 269 meters at 6–minute walking test), nutritional status (stage B vs stage C at PG–SGA test), and muscle strength (handgrip strength test 14.6 vs 8.5 kg). Considering the excellent preoperative optimization response, it was decided to proceed with surgery after a collegial discussion (anesthetist, heart failure cardiologist, surgeon, and patient). Conclusions Multimodal preoperative prehabilitation, based on the collaboration between the Multimodal Preoperative Prehabilitation Unit and Heart Failure Clinic, can effectively improve the preoperative functional capacity of HF patients.

Preoperative Levosimendan therapy reduces postoperative right ventricular failure in patients undergoing left ventricular assist device implantation

Perioperative mortality and complications still remain high after left ventricular assist device (LVAD) implantation, especially in highly compromised patient cohorts. Here, we evaluate the effects of preoperative Levosimendan therapy on peri- and postoperative outcomes after LVAD implantation. We retrospectively analysed 224 consecutive patients with LVAD implantation for end-stage heart failure between November 2010 and December 2019 in our centre with regard to short- and longer-term mortality as well as incidence of postoperative right ventricular failure (RV-F). Out of these, 117 (52.2%) received preoperative i.v. Levosimendan therapy within 7 days before LVAD implantation (Levo group). In-hospital, 30-day and 5-year mortality was comparable (in-hospital mortality: 18.8% vs 23.4%, P = 0.40; 30-day mortality: 12.0% vs 14.0%, P = 0.65; Levo vs control group). However, in the multivariate analysis, preoperative Levosimendan therapy significantly reduced postoperative RV-F but increased postoperative vasoactive inotropic score ([RV-F: odds ratio 2.153, confidence interval 1.146-4.047, P = 0.017; vasoactive inotropic score 24 h post-surgery: odds ratio 1.023, confidence interval 1.008-1.038, P = 0.002). These results were further confirmed by 1:1 propensity score matching of 74 patients in each group. Especially in the subgroup of patients with normal preoperative RV function, the prevalence of postoperative RV-F was significantly lower in the Levo- group as compared to the control group (17.6% vs 31.1%, P = 0.03; respectively). Preoperative Levosimendan therapy reduces the risk of postoperative RV-F, especially in patients with normal preoperative RV function without effects on mortality up to 5 years after LVAD implantation.

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

Endothelial dysfunction (ED) is frequently found in patients with heart failure (HF). Among several pharmacological agents reported to improve endothelial function, levosimendan seems to be a promising one, even though, to date, only two previously published studies have evaluated its effects on ED in these patients. The aim of our pilot study was to further investigate the role of periodic levosimendan infusion on endothelial function in patients affected by advanced HF. In this cross-sectional study, three different groups were enrolled: 20 patients with advanced HF treated with periodic levosimendan (LEVO), 20 patients with HF on optimal medical therapy (OMT), and 20 healthy subjects (control group). ED was evaluated through flow-mediated dilation (FMD) at the level of the brachial artery. The three groups presented similar ages with significant differences in gender distribution, systolic blood pressure, and chronic kidney disease (eGFR < 30 mL/min). In HF patients, ischaemic aetiology was more prevalent in the LEVO group than in the OMT group (60 vs. 40%, p < 0.001). The New York Heart Association (NYHA) functional class was worse in the LEVO group, as well as in NT-proBNP (5636.7 ± 6164.6 ng/dL and 1243.7 ± 1487.2 ng/dL, in the LEVO and OMT groups, respectively, p = 0.005). The FMD was significantly higher in the healthy control group compared to that of the OMT group (15.7 ± 6.4 vs. 9.1 ± 6.0%, p = 0.007) while it showed an intermediate value in LEVO patients (12.4 ± 7.1%) (ANOVA p = 0.010). In conclusion, levosimendan therapy seems to ameliorate endothelial dysfunction related to heart failure. Longitudinal studies in patients on periodic therapy are needed in order to confirm the long-term effects of levosimendan on ED.

Levosimendan Administration May Provide More Benefit for Survival in Patients with Non-Ischemic Cardiomyopathy Experiencing Acute Decompensated Heart Failure.

Background: Acute decompensated heart failure (ADHF) is a life-threatening condition with a high mortality rate. Levosimendan is an effective inotropic agent used to maintain cardiac output and a long-lasting effect. However, only few studies have compared the clinical outcomes, after levosimendan therapy, among etiologies of ADHF. Methods: Between July 2014 and December 2019, 184 patients received levosimendan therapy for ADHF at our hospital. A total of 143 patients had ischemic cardiomyopathy (ICM), and 41 patients had non-ICM (NICM). Data on comorbidities, echocardiographic findings, laboratory findings, use of mechanical devices, consumption of other inotropic or vasopressor agents, frequency of HF hospitalization, cardiovascular (CV) mortality, and all-cause mortality were compared between the ICM and NICM groups. Results: Patients with ICM were older with higher prevalence of diabetes mellitus when compared to patients with NICM. Patients with NICM had a poorer left ventricular ejection fraction (LVEF) and higher left ventricular end-systolic volume when compared to patients with ICM. At the 30 day follow-up period, a lower CV mortality (ICM vs. NICM: 20.9% vs. 5.1%; log-rank p = 0.033) and lower all-cause mortality (ICM vs. NICM: 28.7% vs. 9.8%; log-rank p = 0.018) was observed in the NICM patients. A significantly lower all-cause mortality was noted at 180 day (ICM vs. NICM: 39.2% vs. 22.0%; log-rank p = 0.043) and 1 year (ICM vs. NICM: 41.3% vs. 24.4%; log-rank p = 0.046) follow up in the NICM subgroup. NICM (hazard ratio (HR): 0.303, 95% confidence interval (CI): 0.108–0.845; p = 0.023) and ECMO use (HR: 2.550, 95% CI: 1.385–4.693; p = 0.003) were significant predictors of 30 day all-cause mortality. Conclusions: In our study on levosimendan use for ADHF patients, better clinical outcomes were noted in the NICM population when compared to the ICM population. In the patients with cardiogenic shock or ventilator use, significantly lower incidence of 30 day mortality presented in the NICM population when compared with the ICM population.

Intermittent Levosimendan for Late Right Ventricular Failure in Patients with Left Ventricular Assist Devices

<h3>Purpose</h3> Implantable continuous flow left ventricular assist devices (LVADs) are increasingly used in end-stage heart failure as a bridge-to-transplant (BTT) or destination therapy (DT). One of its most common pitfalls is the development of right ventricular (RV) failure. Despite the fact that right heart failure remains an independent risk factor for mortality, evidence-based therapies are still lacking. The aim of the study is to describe our preliminary single center experience using intermittent infusion of levosimendan in patients with late right heart failure post LVAD implantation. <h3>Methods</h3> We retrospectively revised the data of all patients who received an LVAD in our center and evaluated the patient characteristics and outcomes of those treated with levosimendan for late RV failure. <h3>Results</h3> In the past 10 years (from 2011 until 2020), a total of 130 patients received an LVAD and 8 of them were treated with intermittent levosimendan for RV failure (3 females and 5 males). Two patients had a HeartMate 2 (HM2) and six a HeartMate 3 (HM3). The mean age at LVAD implantation was 59 years and the etiology of their heart failure was coronary artery disease (4/8), myocarditis (2/8) or a non-ischemic dilated cardiomyopathy (2/8). All patients received a monthly dose between 0.1 and 0.3 mcg/kg/min. The average duration of levosimendan therapy during our follow-up was 12 months (ranged from 4 to 26 months). Two patients died because of multi-organ failure due to progression of RV failure, while one of them also suffered hemolysis and several gastrointestinal bleedings. One patient was successfully bridged to a heart transplant (after 13 months of levosimendan therapy), but unfortunately died directly after surgery due to acute graft failure. In one other patient, levosimendan was stopped at the request of the patient based on a subjective lack of efficacy and one episode of ventricular tachycardia. The four remaining patients continue their intermittently therapy and are still alive (2 waiting for the availability of a heart transplant, while the other two have LVAD as destination therapy). <h3>Conclusion</h3> In this first case series, the intermittent use of levosimendan looks promising for the treatment of late RV failure after LVAD.

Intermittent inotropic therapy with levosimendan vs. milrinone in advanced heart failure patients.

AimsRoutine, intermittent inotropic therapy (IIT) is still applied in advanced heart failure (HF) patients either as a bridge to definitive treatment or as a mean to improve quality of life (QOL), despite limited evidence to support its' use. Given recent reports of improved QOL and reduced HF hospitalization, with levosimendan compared with placebo in advanced HF patients, we aimed to assess the effects of switching a small group of milrinone‐treated patients to levosimendan. This was performed as part of a protocol for changing our ambulatory HF clinic milrinone‐based IIT to levosimendan.Methods and resultsSingle‐centre study of consecutive ambulatory advanced HF patients that received ≥4 cycles of once‐weekly milrinone IIT at our HF outpatient clinic, who were switched to levosimendan IIT. All patients had left ventricular ejection fraction ≤35%, elevated B‐natriuretic peptide (BNP), and were in New York Heart Association Classes III–IV despite maximally tolerated guideline directed medical therapy. Patients were evaluated using BNP levels, echocardiography, cardio‐pulmonary exercise test, and HF QOL questionnaire before and after 4 weeks of levosimendan IIT. The cohort included 11 patients, 10 (91%) were male and the mean age was 76 ± 12 years. After 4 weeks of levosimendan therapy, maximal O2 consumption improved in 8/9 (89%) by a mean of 2.28 mL/kg [95% CI −0.22–3.38, P = 0.05]. BNP levels decreased in 9/11 (82%) levosimendan treated patients, from a median of 1015 ng/L [261–1035] to 719 ng/L [294–739], (P < 0.01). QOL as measure by the EQ‐5D‐5L questionnaire improved in 8/11 (82%) patients after levosimendan IIT, by a median of two points [95% CO −4.14–0.37, P = 0.09]. On echocardiography, peak systolic annular velocity (S') increased after levosimendan IIT by an average of 3 cm/s [95% CI 0.16–2.10, P = 0.03].ConclusionsIn this small‐scale study of ambulatory advanced HF patients, we observed improvements in right ventricular systolic function, maximal O2 consumption, and BNP after switching from milrinone to levosimendan based IIT.

Risk Factors for Acute Kidney Injury Requiring Renal Replacement Therapy after Orthotopic Heart Transplantation in Patients with Preserved Renal Function.

Acute kidney injury (AKI), requiring renal replacement therapy (RRT). is a serious complication after orthotopic heart transplantation (HTX). In patients with preexisting impaired renal function, postoperative AKI is unsurprising. However, even in patients with preserved renal function, AKI requiring RRT is frequent. Therefore, this study aimed to identify risk factors associated with postoperative AKI requiring RRT after HTX in this sub-cohort. This retrospective cohort study included patients ≥ 18 years of age with preserved renal function (defined as preoperative glomerular filtration rate ≥ 60 mL/min) who underwent HTX between 2010 and 2021. In total, 107 patients were included in the analysis (mean age 52 ± 12 years, 78.5% male, 45.8% AKI requiring RRT). Based on univariate logistic regression, use of extracorporeal membrane oxygenation, postoperative infection, levosimendan therapy, duration of norepinephrine (NE) therapy and maximum daily increase in tacrolimus plasma levels were chosen to be included into multivariate analysis. Duration of NE therapy and maximum daily increase in tacrolimus plasma levels remained as independent significant risk factors (NE: OR 1.01, 95%CI: 1.00–1.02, p = 0.005; increase in tacrolimus plasma level: OR 1.18, 95%CI: 1.01–1.37, p = 0.036). In conclusion, this study identified long NE therapy and maximum daily increase in tacrolimus plasma levels as risk factors for AKI requiring RRT in HTX patients with preserved renal function.

Levosimendan for Treatment of Primary Graft Dysfunction After Heart Transplantation: Optimal Timing of Application.

Primary graft dysfunction remains a serious problem after heart transplant. Pharmacological treatment with the calcium sensitizer levosimendan may be an additive treatment for primary graft dysfunction. Patients undergoing heart transplant between 2010 and 2020 were retrospectively reviewed and divided depending on postoperative treatment with (n = 41) or without (n = 109) levosimendan. Recipients who received levosi mendan were further divided with regard to timing of levosimendan application (early group: started ≤48 hours posttransplant [n = 23]; late group: started >48 hours posttransplant [n = 18]). Patients who received levosimendan treatment displayed a remarkable incidence (87.8%) of postoperative primary graft dysfunction with need for venoarterial extracorporeal membrane oxygenation and therefore often presented with perioperative morbidity. Patient with early application of levosimendan showed significantly decreased duration of venoarterial extracorporeal membrane oxygenation support (5.1 ± 3.5 days vs 12.6 ± 9.3 days in those with late application; P < .01) and decreased mortality during venoarterial extracorporeal membrane oxygenation support (0.0% vs 33.3% in early vs late group; P < .01). In addition, compared with patients with late levosimendan application, patients with early application needed fewer blood transfusions (P < .05), had shorter ventilation times (279 ± 235 vs 428 ± 293 h; P = .03), and showed a trend of reduced incidence of postoperative renal failure (69.6% vs 94.4%; P = .06). Moreover, survival analyses indicated an increased survival for patients with early start of levosimendan therapy within the first 48 hours after heart transplant (P = .09). Pharmacotherapy with levosimendan may be a promising additive in the treatment of primary graft dysfunction after heart transplant. With administration of levosimendan within the first 48 hours posttransplant, rates of successful weaning from venoarterial extracorporeal membrane oxygenation and outcomes after heart transplant were shown to increase.

Exploratory Assessment of Levosimendan in Infants With Congenital Diaphragmatic Hernia.

Infants with congenital diaphragmatic hernia frequently suffer from cardiac dysfunction and pulmonary hypertension during the postnatal course. With the use of the inodilator levosimendan, a therapeutic approach is available in situations with catecholamine-refractory low-cardiac-output failure and severe pulmonary hypertension. Retrospective single-center cohort study. University-based, tertiary-care children's hospital neonatal ICU. Cohort of 24 infants with congenital diaphragmatic hernia and levosimendan therapy, without underlying major cardiac defect, treated at the University Children´s Hospital Bonn, Germany, between January 2017 and December 2018. None. Twenty-four infants with congenital diaphragmatic hernia were treated with levosimendan (41% of hospitalized congenital diaphragmatic hernia infants in the study period). In 88%, the congenital diaphragmatic hernia was left-sided. The median observed-to-expected lung-to-head ratio was 36%. About 60% of the infants were supported with venovenous extracorporeal membrane oxygenation and the mortality was 38% (9/24 infants). Levosimendan administration was associated with improvement of pulmonary hypertension severity (p = 0.013 and p = 0.000) and right ventricular dysfunction (p = 0.011 and p = 0.000) at 24 hours and 7 days after treatment. Similarly, the prevalence of left ventricular dysfunction decreased from 50% at baseline to 10% after 7 days (p = 0.026). A significant reduction in the peak inspiratory pressure was observed after drug application (p = 0.038) and a significant decrease of the Vasoactive-Inotropic Score was apparent (p = 0.022). A relevant arterial hypotension as a drug-related adverse event occurred in one patient. This is the first study exploring clinical and hemodynamic changes after levosimendan treatment in a cohort of infants with congenital diaphragmatic hernia. An association of levosimendan application and an improvement in pulmonary hypertension, right ventricular, and left ventricular dysfunction were observed within 7 days after drug infusion. However, due to the retrospective design of this study, the results should be interpreted carefully.

Usage and Results of Levosimendan in Ischemic Mitral Valve Surgery

Objective: Large number of comprehensive studies has been carried out on levosimendan. There are many studies on its use, especially in cardiac dysfunction, ischemic cardiac surgery, and heart transplantation surgery. But, there are limited number of studies regarding its use in mitral valve interventions and ischemic mitral dysfunction combined with coronary artery by-pass surgery (CABG). We aimed to investigate the efficacy of levosimendan usage on patients undergone combined coronary artery by-pass grafting and mitral valve surgery because of ischemic mitral dysfunction.Methods: Subsequent patients, who have undergone concurrent CABG and mitral valve repair surgery by a single surgery team, were retrospectively examined. 36 patients were divided into 2 groups; Group 1 (levosimendan therapy group, n=15) and Group 2 (n=21).Results: There was no statistically significant difference between the groups in terms of preoperative characteristics, echocardiographic data of the patients and preoperative medication. Inotrope therapy was required for 12 patients in Group 1, which was statistically higher than Group 2 (n=5, p=0.001). Moreover, IABP following LCOS utilized six and two patients in group 1 and 2 with a statistically significant difference (p=0.03), espectively.Conclusion: We recommend using levosimendan on selected patients for its several beneficial effects. However, we do not satisfied with the treatment because the pathology of all patients was not related to ischemia, more to the alteration of ventricle anatomy with deterioration of diameters.

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

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

Das verspätete Tako-Tsubo-Syndrom – Ein kritischer perioperativer Zwischenfall

The term Takotsubo syndrome (TTS) describes a transient ventricular dysfunction. Symptoms and complication rate are similar to those of a myocardial infarction. An 81-year-old female patient was admitted for thrombendarterectomy of the left femoral artery. Prior to a recent biological aortic valve replacement, coronary heart disease had been ruled out. After induction of anesthesia, relevant arterial hypotension and sinus bradycardia occurred. After catecholamine administration, transient ST segment elevations were observed, which postoperatively developed a myocardial infarction-like dynamic. Echocardiography and values of cardiac enzymes initially revealed no abnormalities. After a symptom-free interval the patient developed severe cardiac decompensation on the third postoperative day. At this point, the clinical picture of TTS was visible. Stabilisation of the clinical condition was achieved with levosimendan therapy. Dynamic ECG changes in the perioperative situation always require differentiated diagnosis and possibly longer monitoring. TTS is a relevant differential diagnosis because it is subject to severe complications.

Baseline pulmonary hypertension in heart transplant recipients: 9 years of experience at Almazov National Medical Research Centre

Objective: to assess the impact of baseline pulmonary hypertension (PH) on early and long-term outcomes following heart transplantation (HT). Materials and methods. From January 2010 to December 2018, 112 HTs were carried out. Based on right heart catheterization results, all recipients were divided into 2 groups: Group 1 with PH (n = 76; mean pulmonary arterial pressure (mPAP) ≥25 mm Hg), Group 2 – without PH (n = 36; MPAP &lt;25 mm Hg). The average age of Group 1 patients was 46.4 ± 14.9 years, baseline pulmonary vascular resistance (PVR) was 3.5 ± 1.5 Wood units, PVR after reversion test (nitric oxide – 80 ppm, iloprost 20 μg) – 2.8 ± 1.0 Wood units, systolic PAP (sPAP) – 50.1 ± 13.4 mm Hg. The average age in Group 2 was 47.3 ± 12.2 years, baseline PVR – 2.1 ± 0.8 Wood units, sPAP – 27.4 ± 5.3 mm Hg. The dynamics in indicators of early postoperative period (duration of mechanical ventilatory support, use of vasodilators and inotropic support and the length of stay in intensive care unit (ICU), 30-day mortality) and long-term post-HT echocardiography results were assessed. Results. Due to acute right-ventricular failure (RVF) developing after heart transplantation, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was done in 8 patients (11%) from Group 1 and one patient (3%) from Group 2. Presence of PH did not affect duration of mechanical ventilatory support, inotropic support, and length of stay in ICU. Levosimendan therapy in the early postoperative period was more often performed in Group 1 (n = 29) than in Group 2 (n = 6) (p = 0.048). Nitric oxide inhalation was also more often administered in Group 1 (n = 54); Group 2 (n = 7), (p = 0.003). Sildenafil therapy after HT was comparable in both groups Group 1 (n = 25); Group 2 (n = 6), (p = 0.048). In early post-HT stages, 14 patients died, 30-day mortality was comparable in both groups (p = 0.12). Six months after HT, no differences were found in the sPAP (p = 0.21) and PVR (p = 0.07) levels. Conclusion. Patients with baseline PH after HT have a more severe early postoperative period, including a higher RVF incidence, with the need for ECMO implantation. A PVR level &gt;3.5 Wood units is not a threshold for HT. Patients with baseline PVR &gt;3.5 Wood units following HT show comparable results with patients without baseline PH. This allows such patients (baseline PVR &gt;3.5 Wood units) to be considered for inclusion in the heart transplant waiting list. In addition, 30-day mortality and duration of mechanical ventilatory support after HT in patients with and without baseline PH did not differ. Regardless of the baseline level of sPAP and PVR, all patients showed improvement in these parameters after HT. Six months after HT, no differences were found in sPAP and PVR levels in the patients, regardless of whether there was baseline PH or not.

Full Recovery After Levosimendan Therapy in a Child with Fulminant Myocarditis

Full Recovery After Levosimendan Therapy in a Child with Fulminant Myocarditis

Myocardial remodeling after kidney transplantation: a case report

BackgroundLupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE) and is often the most serious organ complication and the cause of premature death of such a patient. Most of other organs and systems can be also affected. A typical complication is a cardiovascular involvement leading to the development of heart failure. According to current therapeutic standards, kidney transplantation is the treatment of choice in patients with renal failure in course of LN. On the contrary, a kidney transplantation in a patient with an additional heart disease poses a serious clinical challenge.Case presentationWe present a case of a 49-year-old woman with renal and heart failure following a long-term SLE prepared for kidney transplantation. During the SLE course, the function of the heart and kidneys gradually deteriorated. The patient required the initiation of renal replacement therapy and was dialyzed until a kidney transplantation for 4 years. In the preparation of the patient for the surgical procedure, due to the extremely low ejection fraction, it was decided to include cardioprotective treatment with Levosimendan. The postoperative period was not straightforward but successful. In the monthly and five-month follow-up, a continuous improvement of heart function with normal renal function was noted.ConclusionsKidney transplantation in patients with lupus suffering from heart failure requires the involvement of a team of specialists. Patients with extremely low ejection fraction in the perioperative period should undergo careful hemodynamic supervision in the intensive care unit. Cardioprotective and thus nephroprotective Levosimendan therapy together with optimal fluid and hemodynamic therapy in the peri-transplant period may be a bridge for heart remodeling after kidney transplantation.