Rationale and design of a randomized, double-blind, placebo controlled multicenter trial to study efficacy, security, and long term effects of intermittent repeated levosimendan administration in patients with advanced heart failure: LAICA study.

BACKGROUND: Advanced heart failure (HF) is associated with high morbidity and mortality; it represents a major burden for the health system. Episodes of acute decompensation requiring frequent and prolonged hospitalizations account for most HF-related expenditure. Inotropic drugs are frequently used during hospitalization, but rarely in out-patients. The LAICA clinical trial aims to evaluate the effectiveness and safety of monthly levosimendan infusion in patients with advanced HF to reduce the incidence of hospital admissions for acute HF decompensation. METHODS: The LAICA study is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel group trial. It aims to recruit 213 out-patients, randomized to receive either a 24-h infusion of levosimendan at 0.1 µg/kg/min dose, without a loading dose, every 30 days, or placebo. RESULTS: The main objective is to assess the incidence of admission for acute HF worsening during 12 months. Secondarily, the trial will assess the effect of intermittent levosimendan on other variables, including the time in days from randomization to first admission for acute HF worsening, mortality and serious adverse events. CONCLUSIONS: The LAICA trial results could allow confirmation of the usefulness of intermittent levosimendan infusion in reducing the rate of hospitalization for HF worsening in advanced HF outpatients.

Diastolic Mitral Regurgitation as a Rare Cause of Acute Respiratory Failure Following Complete Atrioventricular Block.

A 77-year-old male presented to the emergency department with dyspnea. A third-degree atrioventricular block was present in the electrocardiogram and an echocardiography showed a moderate mitral regurgitation with a diastolic functional insufficiency. Hemodynamic variations were assessed in the context of heart rhythm disturbances. (Level of Difficulty: Intermediate.).

Cardiogenic shock code 2023. Expert document for a multidisciplinary organization that allows quality care.

Despite the efforts made to improve the care of cardiogenic shock (CS) patients, including the development of mechanical circulatory support (MCS), the prognosis of these patients continues to be poor. In this context, CS code initiatives arise, based on providing adequate, rapid, and quality care to these patients. In this multidisciplinary document we try to justify the need to implement the SC code, defining its structure/organization, activation criteria, patient flow according to care level, and quality indicators. Our specific purposes are: a) to present the peculiarities of this condition and the lessons of infarction code and previous experiences in CS; b) to detail the structure of the teams, their logistics and the bases for the management of these patients, the choice of the type of MCS, and the moment of its implantation, and c) to address challenges to SC code implementation, including the uniqueness of the pediatric SC code. There is an urgent need to develop protocolized, multidisciplinary, and centralized care in hospitals with a large volume and experience that will minimize inequity in access to the MCS and improve the survival of these patients. Only institutional and structural support from the different administrations will allow optimizing care for CS.

Efficacy and safety of intermittent repeated levosimendan infusions in advanced heart failure patients: the LAICA study.

AIMS: The aim of the LAICA study was to evaluate the long-term effectiveness and safety of intermittent levosimendan infusion in patients with advanced heart failure (AdHF). METHODS AND RESULTS: This was a multicentre, randomized, double-blind, placebo-controlled clinical trial of intermittent levosimendan 0.1 µg/kg/min as a continuous 24-h intravenous infusion administered once monthly for 1 year in patients with AdHF. The primary endpoint [incidence of rehospitalization (admission to the emergency department or hospital ward for >12 h) for acute decompensated HF or clinical deterioration of the underlying HF] occurred in 23/70 (33%) of the levosimendan group (Group I) and 12/27 (44%) of the placebo group (Group II) (P = 0.286). The incidence of hospital readmissions for acute decompensated HF (Group I vs. Group II) at 1, 3, 6, and 12 months was 4.2% vs. 18.2% (P = 0.036); 12.8% vs. 33.3% (P = 0.02); 25.7% vs. 40.7% (P = 0.147); 32.8% vs. 44.4% (P = 0.28), respectively. In a secondary pre-specified time-to-event analysis no differences were observed in admission for acute decompensated HF between patients treated with levosimendan compared with placebo (hazard ratio 0.66; 95% CI, 0.32-1.32; P = 0.24). Cumulative incidence for the aggregated endpoint of acute decompensation of HF and/or death at 1 and 3 months were significatively lower in the levosimendan group than in placebo group [5.7% vs. 25.9% (P = 0.004) and 17.1% vs. 48.1% (P = 0.001), respectively], but not at 6 and 12 months [34.2% vs. 59.2% (P = 0.025); 41.4% vs. 66.6% (P = 0.022), respectively]. Survival probability was significantly higher in patients who received levosimendan compared with those who received placebo (log rank: 4.06; P = 0.044). There were no clinically relevant differences in tolerability between levosimendan and placebo and no new safety signals were observed. CONCLUSIONS: In our study, intermittent levosimendan in patients with AdHF produced a statistically non-significant reduction in the incidence of hospital readmissions for acute decompensated HF, a significantly lower cumulative incidence of acute decompensation of HF and/or death at 1 and 3 month of treatment and a significant improvement in survival during 12 months of treatment.

Diurnal variation of soluble CD40 ligand in patients with acute coronary syndrome. Soluble CD40 ligand and diurnal variation.

INTRODUCTION: We sought to investigate whether day-night variations occur in the concentration of circulating soluble CD40 ligand in patients with acute coronary syndrome, as this may have practical implications. MATERIALS AND METHODS: We assessed 70 consecutive ST-segment elevation myocardial infarction patients admitted into the Coronary Care Unit and 50 control subjects. Each subject was studied under strictly controlled light/dark conditions. Blood samples were drawn at 09:00 h (light phase) and 02:00 h (dark phase). Nocturnal blood samples were drawn by a trained nurse, with the help of a minute torch with a dim red light in order to avoid any direct lighting on the patient during sleep. The soluble CD40 ligand was measured using a commercially available ELISA. RESULTS: Soluble CD40 ligand levels showed no diurnal variations in control subjects. In the ST-segment elevation myocardial infarction group, however, soluble CD40 ligand concentration (pg/mL) in the light phase was significantly higher than that in the dark phase (167.3+/-63.2 vs 118.9+/-48.3 pg/mL, p<0.001). CONCLUSIONS: The study shows for the first time the existence of diurnal variations in soluble CD40 ligand levels in ST-segment elevation myocardial infarction patients, which indicates the need for standardizing the time of blood sampling for the assessment of this molecule, at least in studies involving ST-segment elevation myocardial infarction patients.

Long-Term Radiotherapy-Induced Cardiac Complications: A Case Report.

BACKGROUND Tumor disease has improved survival due to therapeutic advances and early diagnosis. However, anti-neoplastic treatment involves generating harmful side effects in the body, both in the short-term and in the long-term. One of the most important side effects is cardiovascular disease after radiotherapy, which in addition to being influenced by classic cardiovascular risk factors, can be also be influenced by anti-neoplastic therapy, and represents the main cause of death after a second cancer. We present a case that synthesizes the most relevant and determining aspects of radiotherapy-induced heart disease. CASE REPORT We present the case of a 48-year-old male with a personal history of mediastinal Hodgkin lymphoma who was treated with local radiotherapy 20 years ago, and who was admitted to hospital due to dyspnea and oppressive chest pain with efforts. He was diagnosed with severe aortic stenosis, and a coronary angiography confirmed the existence of coronary disease. Two years before, he had been admitted to hospital due to syncope and a pacemaker had been implanted. This patient experienced several cardiovascular complications that could be attributed to the radiotherapy treatment received in his past. CONCLUSIONS Radiotherapy shows multiple cardiological complications, especially when applied at the thoracic level. This fact is very relevant, and this report can help determine the aspects of radiotherapy-induced heart disease affecting the mortality and morbidity of these patients.

Prognostic value of admission myeloperoxidase levels in patients with ST-segment elevation myocardial infarction and cardiogenic shock.

Inflammation plays a critical role in acute myocardial infarction. One inflammatory marker is myeloperoxidase (MPO). Its role as a predictor of in-hospital death in patients with ST-segment elevation myocardial infarction (STEMI) presenting with cardiogenic shock (CS) is unclear. Therefore, the aim of this study was to investigate the role of MPO as a predictor of in-hospital death in patients with STEMIs presenting with CS and treated with primary percutaneous coronary intervention. In 38 consecutive patients with CS complicating STEMIs who were treated with primary percutaneous coronary intervention, serum MPO levels were measured at coronary care unit admission using a commercially available enzyme-linked immunosorbent assay. The primary study end point was in-hospital cardiac death. Among the 38 patients included in the study, 20 died during their coronary care unit stays, whereas 18 survived. Compared with patients who survived, patients who died showed, at coronary care unit admission, higher serum MPO levels (81 +/- 28 vs 56 +/- 23 ng/ml, p <0.006). After controlling for different baseline clinical, laboratory, and angiographic variables, baseline serum MPO level was an independent predictor of in-hospital mortality on multivariate analysis (odds ratio 3.9, 95% confidence interval 1.8 to 7.5, p <0.001). In conclusion, admission MPO concentration is an independent predictor of in-hospital mortality in patients with STEMIs presenting with CS.

Relation of ischemia-modified albumin levels and left ventricular systolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Ischemia-modified albumin (IMA) has been shown to be elevated in patients after percutaneous coronary intervention (PCI). Our goal was to investigate the association between IMA levels and left ventricular ejection fraction in patients with ST-segment elevation myocardial infarction (STEMI) treated with PCI and who developed heart failure during their Coronary Care Unit (CCU) stay. METHODS: We assessed 75 patients with a first STEMI. Presence of heart failure was assessed during CCU admission, and patients were subdivided into 2 groups: group A (n=45) comprised patients in Killip class I, and group B (n=30) Killip classes>I. Serum IMA concentration was measured within the first 15 min post-PCI. The IMA measured was performed using an indirect method based in the Albumin Cobalt Binding (ACB) colorimetric assay. The ideal cutoff value of IMA was calculated by the receiver operating characteristic (ROC) curve analysis. RESULTS: Serum IMA concentrations were significantly higher in group B than in group A (0.37+/-0.09 vs 0.30+/-0.06 (A.U.); p<0.0001). The sensitivity and specificity of IMA for heart failure were 93.3% and 37.7%, respectively, at 0.31 A.U. Multivariable adjustment IMA showed a significant inverse correlation with left ventricular ejection function (r=-0.32; p=0.004). On multivariable analysis both IMA (OR=2.1, 95%CI: 1.2 to 3.9, p<0.001) and left ventricular ejection function (OR=1.7, 95%CI: 1.1 to 2.1, p<0.01) correlated with the occurrence of heart failure. CONCLUSION: In patients with STEMI undergoing PCI, serum IMA concentrations are significantly related to LVEF and represent an early marker of left ventricular dysfunction.

Soluble CD40 ligand:interleukin-10 ratio predicts in-hospital adverse events in patients with ST-segment elevation myocardial infarction.

INTRODUCTION: The balance between pro-inflammatory and anti-inflammatory molecules is likely to modulate the processes that lead to atherogenesis and rapid coronary artery disease progression. We sought to compare the positive predictive values of serum soluble CD40 ligand (sCD40L)/interleukin-10 (IL-10) ratio, versus individual sCD40L, and IL-10 measurements regarding in-hospital events in patients admitted into the hospital with ST-segment elevation myocardial infarction (STEMI). METHODS: We recruited 96 patients with STEMI. sCD40L and IL-10 were measured at hospital admission in every patient. The composite of in-hospital death and heart failure represented the study end-point. Heart failure was defined as Killip class>1. Multivariable logistic regression analysis was performed to identify independent variables related to in-hospital events. RESULTS: Thirty two patients (33%) achieved the study end-point and 64 (67%) had no adverse events during hospital admission. IL-10 levels (pg/ml) were lower (28.2+/-9.8 versus 33.24+/-11.3, p=0.03) and sCD40L levels (pg/ml) higher (156.8+/-54.2 versus 135.4+/-38.70, p=0.02) in patients with events compared to those without events. Significantly higher odd ratios were found for sCD40L/IL-10 ratio (OR=2.10, 95% CI: 1.90 to 2.80, p=0.01) compared to individual sCD40L (OR=1.40, 95% CI: 0.90 to 2.20, p=0.08) and IL-10 (OR=0.70, 95% CI: 0.50 to 0.93, p=0.02) measurements. CONCLUSION: Our study showed that serum ratio of sCD40L/IL-10 is a better independent predictor of in-hospital adverse events than individual sCD40L and IL-10 measurements in patients with STEMI.

Relation of nocturnal melatonin levels to serum matrix metalloproteinase-9 concentrations in patients with myocardial infarction.

INTRODUCTION: The aims of the present study were to characterize the day/night variation of matrix metalloproteinase (MMP)-9 in patients who have developed ST-segment elevation myocardial infarction (STEMI), in response to light/dark differences in circulating melatonin and to assess whether melatonin, a day/night variation regulator, modulates the nocturnal inflammatory changes in patients who have STEMI. METHODS: The study included 75 patients diagnosed with STEMI and 75 control subjects. Each subject was studied under strictly controlled light/dark conditions. Blood samples for measurement of MMP-9 and melatonin were collected at 09:00 a.m. (light period) and 02:00 a.m. (dark period). RESULTS: In patients with STEMI, melatonin concentrations maintained a light/dark variation but the difference between nocturnal and diurnal levels was smaller than that in controls (p<0.001). In contrast to melatonin, serum MMP-9 concentrations showed no day/night variation in control subjects. MMP-9 concentrations were significantly higher in patients with STEMI than in control subjects. In the STEMI subjects, MMP-9 serum concentrations in the light period were significantly higher than those during the dark phase (291.1+/-59.5 vs. 261.8+/-57.8 ng/ml, p<0.01). Furthermore in the control subjects there was no correlation between MMP-9 and melatonin levels, while in the STEMI group there was a significant correlation between these parameters (Pearson's r=0.40, p<0.0004). CONCLUSIONS: Our results suggest that the light/dark variations in endogenous MMP-9 production in patients who have STEMI might be associated, at least in part, to the day/night variation of melatonin.

A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocaRdial Infarction undergoing primary Angioplasty The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial: study design and rationale.

BACKGROUND: Experimental studies have documented the beneficial effects of the endogenously produced antioxidant, melatonin, in reducing tissue damage and limiting cardiac pathophysiology in models of experimental ischemia-reperfusion. Melatonin confers cardioprotection against ischemia-reperfusion injury most likely through its direct free radical scavenging activities and its indirect actions in stimulating antioxidant enzymes. These actions of melatonin permit it to reduce molecular damage and limit infarct size in experimental models of transient ischemia and subsequent reperfusion. STUDY DESIGN: The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial is an unicenter, prospective, randomized, double-blind, placebo-controlled, phase 2 study of the intravenous administration of melatonin. The primary efficacy end point of this study is to determine whether melatonin treatment reduces infarct size determined by the cumulative release of alpha-hydroxybutyrate dehydrogenase (area under the curve: 0 to 72 h). Other secondary end points will be the clinical events occurring within the first 90 days: death, sustained ventricular arrhythmias, resuscitation from cardiac arrest, cardiogenic shock, heart failure, major bleedings, stroke, need for revascularization, recurrent ischemia, re-infarctions and rehospitalization. IMPLICATIONS: The MARIA trial tests a novel pharmacologic agent, melatonin, in patients with acute myocardial infarction and the hypothesis that it will confer cardioprotection against ischemia-reperfusion injury. If successful, the finding would support the use of melatonin in therapy of ischemic-reperfusion injury of the heart.

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy.

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.

Cardiogenic shock after primary percutaneous coronary intervention: Effects of levosimendan compared with dobutamine on haemodynamics.

BACKGROUND: Levosimendan is a new calcium sensitizer with positive inotropic properties. Cardiac power output (CPO) has been shown to be instrumental in the diagnosis of cardiogenic shock (CS) and is an important determinant of outcomes. AIMS: To evaluate the haemodynamic effects of levosimendan compared to dobutamine in acute myocardial infarction (AMI) patients revascularised by primary percutaneous coronary intervention (PCI), who developed CS. METHODS AND RESULTS: Twenty two consecutive AMI patients revascularised by PCI, who developed CS, were randomly assigned to levosimendan (24 microg kg(-1) bolus plus 24-h continuous infusion 0,1 microg kg(-1) min(-1)) or dobutamine (initial dose 5 microg kg(-1) min(-1), with a maximum dose adjustment in order to reach the desired haemodynamic effect). Evaluations were performed from baseline to 30 h. The primary end-point was an increase > or =30% in CPO, after 24 h of therapy. The baseline clinical and haemodynamic characteristics were similar in both groups. Levosimendan had a consistently better effect on CPO than dobutamine, while the decrease in PCWP was similar. CONCLUSION: The primary objective of our study was achieved better by the end of the 24 h infusion of levosimendan than by dobutamine.

Pharmacologic treatment of heart failure due to ventricular dysfunction by myocardial stunning: potential role of levosimendan.

The treatment of heart failure continues to pose a real challenge for clinicians. This condition is sometimes reversible and therapy should therefore pursue this outcome. In the context of coronary ischemic syndromes, myocardial stunning can cause heart failure and even cardiogenic shock, with important prognostic repercussions. Myocardial stunning is mainly due to calcium overload in the cytosol of myocardial cells, the loss of myofilaments and their reduced sensitivity to calcium. Enhanced immune activation with inflammatory phenomena also plays an important role in the pathophysiology of cardiac dysfunction. Increasing evidence has shown that the myocardial ATP-dependent potassium channel (K(ATP)) plays an important role in many myocardial cell functions and that it is involved in ischemia-reperfusion injury and myocardial stunning. K(ATP) is thus considered a therapeutic target in this setting. Currently used inotropic drugs improve contractility by increasing intracellular concentrations of free calcium, but they increase myocardial consumption of energy and even produce arrhythmia; therefore, in this clinical context, they do not seem to be 'pathophysiologically correct' drugs. Levosimendan, a new calcium-sensitizing agent, increases contractility by enhancing the sensitivity of myofilaments to calcium by binding to the C cardiac troponin in cardiac muscle in a calcium-dependent way. Levosimendan also exerts a coronary and systemic vasodilatory effect through its K(ATP) channel-opening properties and may exert other cardioprotective actions through this mechanism. Levosimendan produces positive hemodynamic effects without increasing myocardial oxygen demand or causing arrhythmias. Intravenous levosimendan is generally well tolerated and has been approved by several European countries, and recently recommended in European Society of Cardiology guidelines, as inotropic therapy for the short-term treatment of acute severe decompensated heart failure in adults. Randomized, double-blind trials have shown that levosimendan is not only more clinically and hemodynamically effective but also that it significantly reduces morbidity and mortality when compared with dobutamine or placebo. Clinical trials addressing the use and efficacy of intravenous levosimendan in acute heart failure in patients with systolic dysfunction or cardiogenic shock due to myocardial stunning are scarce. Beneficial effects on myocardial contractility in patients with myocardial stunning have only been shown in small clinical trials. A positive experience with levosimendan in a small series of patients with cardiogenic shock complicating ST-elevation myocardial infarction suggests that the use of this drug in cardiogenic shock should be further evaluated.

[Influence of diabetes mellitus on the management and prognosis of non-ST-elevation acute coronary syndrome]. / Influencia de la diabetes mellitus en el tratamiento y el pronóstico del síndrome coronario agudo sin elevación del segmento ST.

The presence of diabetes mellitus worsens prognosis in acute coronary syndromes. The aim of our study was to analyze retrospectively the influence of diabetes mellitus on the management and prognosis of patients with non-ST-segment elevation acute coronary syndrome. We compared the baseline clinical characteristics of 273 patients (93 diabetic and 180 non-diabetic) admitted consecutively to our department with the diagnosis of non-ST-segment elevation acute coronary syndrome. In both groups, we assessed the medical treatment given during hospitalization and the use of coronary angiography, percutaneous coronary intervention, and coronary artery bypass grafting. Finally, we determined the incidence of heart failure during hospitalization and mortality at 28 days and 6 months in both groups. Multifactorial analysis revealed that diabetes was an independent risk factor for mortality during the study period. Data from our registry indicate that these findings were not associated with more extensive use of interventions in diabetic patients.

[Association between serum interleukin 10 level and development of heart failure in acute myocardial infarction patients treated by primary angioplasty]. / Asociación entre concentraciones séricas de interleucina 10 y desarrollo de insuficiencia cardíaca en pacientes con infarto agudo de miocardio tratados con angioplastia primaria.

INTRODUCTION AND OBJECTIVES: Interleukin 10 (IL-10) is an anti-inflammatory cytokine that inhibits the synthesis of proinflammatory cytokines. It has been shown that IL-10 is released into the circulation during post-ischemic myocardial reperfusion. The objective of this study was to determine whether the serum IL-10 concentration in patients with acute myocardial infarction who were undergoing primary angioplasty was related to the subsequent presence or absence of heart failure. PATIENTS AND METHOD: The study included 65 patients who underwent successful primary angioplasty. During their subsequent stay in the coronary unit, their maximum degree of heart failure was recorded. Patients were then divided into 2 groups: group A patients were in Killip class I and group B patients in Killip classes II-IV. The serum IL-10 concentration was measured during the 24 hours following admission to the coronary unit. RESULTS: The 2 groups were similar with regard to age, sex, and coronary risk factors. The IL-10 concentration was significantly higher in the group of patients with acute myocardial infarction without heart failure than in the group with heart failure (30.4+/-10.8 vs 19.8+/-7.9 pg/mL; P<.001). CONCLUSIONS: In patients with acute myocardial infarction who had undergone successful primary angioplasty, the serum IL-10 concentration measured during the following 24 hours was significantly higher in those who did not develop heart failure. These findings suggest that this anti-inflammatory cytokine has a protective effect on the myocardium during ischemia or reperfusion, or both.

Levosimendan improves hemodynamic status in critically ill patients with severe aortic stenosis and left ventricular dysfunction: an interventional study.

AIMS: To study the hemodynamic effect of levosimendan administration in acute heart failure patients with severe aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF). METHODS: Hemodynamic response to 24 h intravenous levosimendan infusion (0.1 µg/kg/min without a loading dose) in patients with severe AS (aortic valve area ≤1 cm(2) , time-velocity integral between left ventricular out-flow tract and aortic valve <0.25), reduced LVEF (≤40%), and a depressed cardiac index (CI) <2.2 L/min/m(2) was determined in a sequential group of nine patients aged 76 ± 10 years (5 men). RESULTS: Baseline mean ejection fraction was 33 ± 0.7%; mean aortic valve area was 0.37 ±0.11 cm(2) /m(2) ; peak and mean gradients of 63.6 ± 20.53 and 36.7 ± 12.62 mmHg, respectively; and mean CI was 1.65 ± 0.20 L/min/m(2) . At 6 and 12 h of levosimendan therapy, mean CI had increased to 2.00 ± 0.41 L/min/m(2) (P = 0.02) and 2.17 ± 0.40 L/min/m(2) (P = 0.01), respectively. At 24 h, mean CI had increased further to 2.37 ± 0.49 L/min/m(2) (P = 0.01). A significant beneficial effect was also observed in pulmonary capillary wedge pressure, pulmonary artery mean pressure, central venous pressure, systemic vascular resistances, pulmonary vascular resistances, stroke volume index, left ventricular stroke work index. NTproBNP levels decreased at 24 h of levosimendan treatment. Levosimendan infusion was also well tolerated. Five patients subsequently underwent aortic valve surgery replacement. One died (of postoperative multiorgan failure). At 30 days, overall survival was 75%. CONCLUSIONS: Levosimendan administration improves hemodynamic parameters in critically ill patients with severe AS and reduced LVEF. In our study, it provides a safe and effective bridge to aortic-valve replacement or oral vasodilator therapy in surgical contraindicated patients. A controlled study is needed to confirm these preliminary findings.