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Among patients with heart failure and a reduced ejection fraction, those who received the cardiac myosin activator omecamtiv mecarbil had a lower incidence of a composite of heart-failure events or cardiovascular death at a median of 22 months than those who received placebo.

Patients with cardiogenic shock were assigned to receive milrinone or dobutamine for inotropic support. There was no significant difference between the two groups in the composite primary outcome of in-hospital death from any cause or cardiovascular or renal events.

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 . . .

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Although it has been widely appreciated that obesity is a major risk factor for CVD, treatments that produce effective, durable weight loss and the impact of weight reduction in reducing cardiovascular risk have been elusive. Instead, progress in CVD risk reduction has been achieved through medications indicated for controlling lipids, hyperglycemia, blood pressure, heart failure, inflammation, and/or thrombosis. Obesity has been implicated as promoting all these issues, suggesting that sustained, effective weight loss may have independent cardiovascular benefit. GLP-1 receptor agonists (RAs) reduce weight, improve glycemia, decrease cardiovascular events in those with diabetes, and may have additional cardioprotective effects. The GLP-1 RA semaglutide is in phase 3 studies as a medication for obesity treatment at a dose of 2.4 mg subcutaneously (s.c.) once weekly. Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) is a randomized, double-blind, parallel-group trial testing if semaglutide 2.4 mg subcutaneously once weekly is superior to placebo when added to standard of care for preventing major adverse cardiovascular events in patients with established CVD and overweight or obesity but without diabetes. SELECT is the first cardiovascular outcomes trial to evaluate superiority in major adverse cardiovascular events reduction for an antiobesity medication in such a population. As such, SELECT has the potential for advancing new approaches to CVD risk reduction while targeting obesity.

ObjectiveTo determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation.DesignDouble-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment.Setting10 sites across Europe and Canada.ParticipantsInfants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage.InterventionParticipants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management).Primary outcomeSurvival to 36 weeks of PMA without severe brain injury.ResultsThe trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038).ConclusionThough this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area.Trial registration number NCT01482559, EudraCT 2010-023988-17.

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 . . .

Background The administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts. Methods This was a single-center, double-blind, randomized, placebo-controlled trial. Patients ≤ 48 months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48 h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study. Results A total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19–1.13; p  = 0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14–3.69, p  = 0.693), duration of mechanical ventilation (median, 47.5 h and 39.5 h, respectively; p  = 0.532), ICU stay (median, 114.5 h and 118 h, respectively; p  = 0.442), and hospital stay (median, 20 days and 20 days, respectively; p  = 0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS. Conclusions Prophylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo. Trial registration Name of the registry: Safety evaluation and therapeutic effect of levosimendan on the low cardiac output syndrome in patients after cardiopulmonary bypass. Trial registration number: ChiCTR1800016594. Date of registration: 11 June 2018. URL of trial registry record: http://www.chictr.org.cn/index.aspx

We aimed to evaluate the association between levosimendan treatment and acute kidney injury (AKI) as well as assess the clinical sequelae of AKI in cardiac surgery patients with depressed left ventricular function (ejection fraction <35%). Patients in the LEVO-CTS trial undergoing on-pump coronary artery bypass grafting (CABG), valve, or CABG/valve surgery were stratified by occurrence and severity of postoperative AKI using the AKIN classification. The association between levosimendan infusion and AKI was modeled using multivariable regression. Among 854 LEVO-CTS patients, 231 (27.0%) experienced postoperative AKI, including 182 (21.3%) with stage 1, 35 (4.1%) with stage 2, and 14 (1.6%) with stage 3 AKI. The rate of AKI was similar between patients receiving levosimendan or placebo. The odds of 30-day mortality significantly increased by AKI stage compared to those without AKI (stage 1: adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI] 0.8-4.9; stage 2: aOR 9.1, 95% CI 3.2-25.7; stage 3: aOR 12.4, 95% CI 3.0-50.4). No association was observed between levosimendan, AKI stage, and odds of 30-day mortality (interaction P = .69). Factors independently associated with AKI included increasing age, body mass index, diabetes, and increasing baseline systolic blood pressure. Increasing baseline eGFR and aldosterone antagonist use were associated with a lower risk of AKI. Postoperative AKI is common among high-risk patients undergoing cardiac surgery and associated with significantly increased risk of 30-day death or dialysis. Levosimendan was not associated with the risk of AKI.

Background Cardiogenic shock (CS) occurs in 5–10% of patients with acute myocardial infarction (AMI), and the condition is associated with a 30-day mortality rate of up to 50%. Most of the AMI patients are in SCAI SHOCK stage B upon hospital arrival, but some of these patients will progression through the stages to overt shock (SCAI C-E). Around one third of patients who develop CS are not in shock at the time of hospital admission. Pro-B-type natriuretic peptide (proband) is a biomarker closely related to CS development. The aim of this study is to investigate the potential for preventing progression of hemodynamic instability by early inotropic support with low-dose dobutamine infusion administrated after revascularization in AMI patients with intermediate to high risk of in-hospital CS development. Methods This investigator-initiated, double-blinded, placebo-controlled, randomized, single-center, clinical trial will include 100 AMI patients (≥ 18 years) without CS at hospital admission and at intermediate-high risk of in-hospital CS development (ORBI risk score ≥ 10). Patients will be randomized in a 1:1 ratio to a 24 h intravenous (IV) infusion of dobutamine (5 μg/kg/min) or placebo (NaCl) administrated after acute percutaneous coronary intervention (PCI) (< 24 h from symptom onset). Blood samples are drawn at time points from study inclusion (before infusion, 12, 24, 36, and 48 h). The primary outcome is peak plasma proBNP within 48 h after infusion as a surrogate-measure for the hemodynamic status. Hemodynamic function will be assessed pulse rate, blood pressure, and lactate within 48 h after infusion and by transthoracic echocardiography (TTE) performed after 24–48 h and at follow-up after 3 months. Markers of cardiac injury (troponin T and creatine kinase MB (CK-MB)) will be assessed. Discussion Early inotropic support with low-dose dobutamine infusion in patients with AMI, treated with acute PCI, and at intermediate-high risk of in-hospital CS may serve as an intervention promoting hemodynamic stability and facilitating patient recovery. The effect will be assessed using proBNP as a surrogate marker of CS development, hemodynamic measurements, and TTE within the initial 48 h and repeated at a 3-month follow-up. Trial registration The Regional Ethics Committee : H-21045751. EudraCT: 2021–002028-19. ClinicalTrials.gov: NCT05350592, Registration date: 2022-03-08. WHO Universal Trial Number: U1111-1277–8523.

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.