Explore the vast range of titles available.

In a randomized trial, 506 patients requiring perioperative hemodynamic support after cardiac surgery were assigned to receive levosimendan or placebo in addition to standard care. There was no significant between-group difference in 30-day mortality. Every year, more than 1 million patients undergo cardiac surgery in the United States and Europe. 1 Acute perioperative left ventricular dysfunction is a major complication affecting up to 20% of such patients 2 , 3 and is associated with increased mortality. 4 Inotropic drugs (catecholamines and phosphodiesterase type 3 [PDE-3] inhibitors) are the cornerstone of postoperative hemodynamic support. 3 , 5 However, no randomized, controlled trials have shown the superiority of any inotropic agent in terms of major clinical outcomes. Furthermore, meta-analyses and observational studies suggest that catecholamines and PDE-3 inhibitors may increase mortality. 6 , 7 Levosimendan (Simdax, Orion) is an inotropic agent that has been . . .

In this trial, 882 cardiac surgical patients with left ventricular dysfunction were assigned to levosimendan or placebo. There was no between-group difference in the rate of death, renal-replacement therapy, perioperative myocardial infarction, or mechanical cardiac assist device use. Cardiac surgery with the use of cardiopulmonary bypass is a common procedure, with more than 1 million operations performed annually in the United States and Europe. 1 Increasingly, patients who are referred for cardiac surgery are older and have multiple coexisting conditions, as compared with those who were referred for these procedures in the past. 2 These patients benefit from cardiac surgery but are at increased risk for perioperative complications that result in high morbidity and mortality and a high use of health care services. 2 – 4 One such complication, the low cardiac output syndrome, occurs in 3 to 14% of patients who . . .

Levosimendan, a novel calcium sensitiser, improves myocardial contractility without causing an increase in myocardial oxygen demand. We compared the effects of levosimendan and dobutamine on haemodynamic performance and clinical outcome in patients with low-output heart failure. Patients were recruited into a multicentre, randomised, double-blind, double-dummy, parallel-group trial. Under continuous haemodynamic monitoring, an initial loading dose of levosimendan of 24 μg/kg was infused over 10 min, followed by a continuous infusion of 0·1 μg kg−1 min−1 for 24 h. Dobutamine was infused for 24 h at an initial dose of 5 μg kg−1 min−1 without a loading dose. The infusion rate was doubled if the response was inadequate at 2 h. The primary endpoint was the proportion of patients with haemodynamic improvement (defined as an increase of 30% or more in cardiac output and a decrease of 25% or more in pulmonary-capillary wedge pressure) at 24 h. Analyses were by intention to treat. 103 patients were assigned levosimendan and 100 dobutamine. The primary haemodynamic endpoint was achieved in 29 (28%) levosimendan-group patients and 15 (15%) in the dobutamine group (hazard ratio 1·9 [95% CI 1·1–3·3]; p=0·022). At 180 days, 27 (26%) levosimendan-group patients had died, compared with 38 (38%) in the dobutamine group (0·57 [0·34–0·95]; p=0·029). In patients with severe, low-output heart failure, levosimendan improved haemodynamic performance more effectively than dobutamine. This benefit was accompanied by lower mortality in the levosimendan group than in the dobutamine group for up to 180 days.

Calcium desensitization plays an important part in the pathophysiology of septic myocardial depression. We postulated that levosimendan, a new calcium sensitizer, would be beneficial in sepsis-induced cardiac dysfunction. Prospective, randomized, controlled study in two university hospital intensive care units. Twenty-eight patients with persisting left ventricular dysfunction related to septic shock after 48 h of conventional treatment including dobutamine (5 microg/kg per minute). After 48 h of conventional treatment patients were randomized to receive a 24-h infusion of either levosimendan (0.2 microg/kg per minute, n=15) or dobutamine (5 microg/kg per minute, n=13). Data from right heart catheterization, echocardiography, gastric tonometry, laser-Doppler flowmetry, and lactate concentrations and creatinine clearance were obtained before and after the 24-h drug infusion. Dobutamine did not change systemic or regional hemodynamic variables. By contrast, at the same mean arterial pressure levosimendan decreased pulmonary artery occlusion pressure and increased cardiac index. Levosimendan decreased left ventricular end-diastolic volume and increased left ventricular ejection fraction. Levosimendan increased gastric mucosal flow, creatinine clearance, and urinary output while it decreased lactate concentrations. These findings show that levosimendan improves systemic hemodynamics and regional perfusion in patients with septic cardiac dysfunction under conditions where administration of 5 microg/kg dobutamine per minute is no longer efficacious. Accordingly, our results suggest that levosimendan can be an alternative to the strategy of increasing the dose of dobutamine under such conditions.

Objective To investigate the therapeutic effect of levosimendan on hemodynamics in patients undergoing major cardiac surgery and presenting with acute postoperative heart failure. Methods The subjects of the study were 160 patients with severe cardiac conditions who underwent surgery and had acute heart failure. Eighty cases each were assigned to the research and control groups using a random number table. Document the general patient data for each of the two groups; compare the clinical outcomes of the two groups. The hemodynamic states of the two groups were compared both before and after therapy. 48 h after surgery, echocardiography was performed in both groups to determine cardiac function. 48 h after surgery, N -terminal pro-brain B -type natriuretic peptide (NT-Pro-BNP) levels were compared between the two groups. Results The overall effective rate was significantly higher in the research group (92.5%) compared to the control group (76.25%, P  < 0.05). Post-treatment, the research group demonstrated a significant reduction in CVP (9.25 ± 2.11 cmH2O vs. 11.36 ± 3.08 cmH2O, P  < 0.001), heart rate (100.30 ± 8.69 bpm vs. 105.74 ± 7.69 bpm, P  < 0.001), and lactic acid levels (1.68 ± 0.59 mmol/L vs. 2.69 ± 0.55 mmol/L, P  < 0.001). The research group also showed improvements in SBP (117.23 ± 8.74 mmHg vs. 113.25 ± 7.55 mmHg, P  = 0.002) and urine output (4.21 ± 1.76 mL/kg/h vs. 3.65 ± 1.23 mL/kg/h, P  = 0.021). Cardiac function indicators 48 h after surgery indicated a higher LVEF (55.21 ± 8.04% vs. 47.18 ± 6.60%, P  < 0.001) and lower LVEDVi and LVESVi in the research group ( P  < 0.001 for both). NT-Pro-BNP levels were significantly lower in the research group (6010.19 ± 1208.52 pg/mL vs. 9663.21 ± 2391.34 pg/mL, P  < 0.001). The incidence of complications was lower in the research group (5% vs. 22.5%, P  = 0.001). Conclusion Cardiac surgery patients are prone to complications with acute heart failure after surgery. Treatment with levosimendan can significantly improve clinical efficacy and reduce complications. It can also effectively improve patients' cardiac function and promote hemodynamic stability.

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

Purpose To evaluate the safety and efficacy of levosimendan in neonates with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods Neonates undergoing risk-adjusted classification for congenital heart surgery (RACHS) 3 and 4 procedures were randomized to receive either a 72 h continuous infusion of 0.1 μg/kg/min levosimendan or standard post-CPB inotrope infusion. Results Sixty-three patients (32 cases and 31 controls) were recruited. There were no differences between groups regarding demographic and baseline clinical data. No side effects were observed. There were no significant differences in mortality (1 vs. 3 patients, p  = 0.35), length of mechanical ventilation (5.9 ± 5 vs. 6.9 ± 8 days, p  = 0.54), and pediatric cardiac intensive care unit (PCICU) stay (11 ± 8 vs. 14 ± 14 days, p  = 0.26). Low cardiac output syndrome occurred in 37 % of levosimendan patients and in 61 % of controls ( p  = 0.059, OR 0.38, 95 % CI 0.14–1.0). Postoperative heart rate, with a significant difference at 6 ( p  = 0.008), 12 ( p  = 0.037), and 24 h ( p  = 0.046), and lactate levels, with a significant difference at PCICU admission ( p  = 0.015) and after 6 h ( p  = 0.048), were lower in the levosimendan group. Inotropic score was significantly lower in the levosimendan group at PCICU admission, after 6 h and after 12 h, ( p  < 0.0001). According to multivariate analysis, a lower lactate level 6 h after PCICU admission was independently associated with levosimendan administration after correction for CPB time and the need for deep hypothermic circulatory arrest. Conclusions Levosimendan infused in neonates undergoing cardiac surgery was well tolerated with a potential benefit of levosimendan on postoperative hemodynamic and metabolic parameters of RACHS 3–4 neonates.

Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Double-blind, placebo-controlled, multicenter randomized trial. Tertiary care hospitals. Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.

No data from controlled trials exists regarding the inflammatory response in patients with de novo heart failure (HF) complicating ST-elevation myocardial infarction (STEMI) and a possible role in the recovery of contractile function. We therefore explored the time course and possible associations between levels of inflammatory markers and recovery of impaired left ventricular function as well as levosimendan treatment in STEMI patients in a substudy of the LEvosimendan in Acute heart Failure following myocardial infarction (LEAF) trial. A total of 61 patients developing HF within 48 hours after a primary PCI-treated STEMI were randomised double-blind to a 25 hours infusion of levosimendan or placebo. Levels of IL-6, CRP, sIL-6R, sgp130, MCP-1, IL-8, MMP-9, sICAM-1, sVCAM-1 and TNF-α were measured at inclusion (median 22 h, interquartile range (IQR) 14, 29 after PCI), on day 1, day 2, day 5 and 6 weeks. Improvement in left ventricular function was evaluated as change in wall motion score index (WMSI) by echocardiography. Only circulating levels of IL-8 at inclusion were associated with change in WMSI from baseline to 6 weeks, r = ÷ 0.41 (p = 0.002). No association, however, was found between IL-8 and WMSI at inclusion or peak troponin T. Furthermore, there was a significant difference in change in WMSI from inclusion to 6 weeks between patients with IL-8 levels below, compared to above median value, ÷ 0.44 (IQR ÷ 0.57, ÷ 0.19) vs. ÷ 0.07 (IQR ÷ 0.27, 0.07), respectively (p < 0.0001). Levosimendan did not affect the levels of inflammary markers compared to control. High levels of IL-8 in STEMI patients complicated with HF were associated with less improvement in left ventricular function during the first 6 weeks after PCI, suggesting a possible role of IL-8 in the reperfusion-related injury of post-ischemic myocardium. Further studies are needed to confirm this hypothesis. ClinicalTrials.gov NCT00324766.

Background Levosimendan is a promising new inodilator agent but its effectiveness in peripartum cardiomyopathy (PPCM) has not been tested in a clinical trial. The authors sought to evaluate the effect of levosimendan therapy and to determine the predictors of clinical outcome in patients with PPCM. Methods and results The authors prospectively randomized 24 consecutive women with PPCM. Twelve patients (control group) were randomized to conventional heart failure therapy and 12 patients (levosimendan group) were randomized to levosimendan in addition to the conventional therapy. Mean follow-up period was 20.9 ± 9 months (ranged 12–38 months). The two groups did not differ in baseline demographic and echocardiographic characteristics. Eleven patients (45.8%) recovered completely (6 in control group and 5 in levosimendan group, p  > 0.05), 6 died (25%) (3 in control group and 3 in levosimendan group), and 7 (29.1%) were left with persistent left ventricular dysfunction (PLVD) (3 in control group and 4 in levosimendan group, p  > 0.05). There were significant differences in baseline characteristics between deceased patients and survivors including left ventricular end-diastolic diameter (7.1 ± 0.6 vs. 6.4 ± 0.5 cm, p  = 0.031), left ventricular end-systolic diameter (LVESD) (6.4 ± 0.8 vs. 5.5 ± 0.6 cm, p  = 0.027), left ventricular ejection fraction (LVEF) (19.7 vs. 27.4%, p  = 0.025), and left atrial diameter (4.9 ± 0.3 vs. 4.3 ± 0.4 cm, p  = 0.011). Conclusions Addition of levosimendan to conventional therapy did not improve outcome in patients with PPCM. In patients with PLVD or patients who died, LVEF, LVESD and left atrial diameter were worse than those with complete resolution.