title: Effects of serial levosimendan infusions on left ventricular performance and plasma biomarkers of myocardial injury and neurohormonal and immune activation in patients with advanced heart failure.
abstract: BACKGROUND
  Levosimendan is a novel inodilator that improves central haemodynamics and symptoms of patients with decompensated chronic heart failure. The role, however, of repeated levosimendan infusions in the management of these patients has not yet been properly assessed.
  
  
  OBJECTIVE
  This randomised placebo-controlled trial investigated the effects of serial levosimendan infusions on cardiac geometry and function, and on biomarkers of myocardial injury and neurohormonal and immune activation (troponin T, N-terminal B-type natriuretic pro-peptide (NT-proBNP), C reactive protein (CRP) and interleukin (IL) 6) in patients with advanced heart failure.
  
  
  METHODS
  25 patients with decompensated chronic heart failure were randomised (2:1) to receive five serial 24-h infusions (every 3 weeks) of either levosimendan (n = 17) or placebo (n = 8), and were evaluated echocardiographically and biochemically before and after each drug infusion and 30 days after the final infusion.
  
  
  RESULTS
  Following treatment, cardiac end-systolic and end-diastolic dimension and volume indices were significantly reduced only in the levosimendan-treated patients (p<0.01). A significant decrease in NT-proBNP (p<0.01), high-sensitivity CRP (p<0.01) and plasma IL6 (p = 0.05) was also observed in the levosimendan group, whereas these markers remained unchanged in the placebo group; similar changes were observed after each drug infusion. Although the number of patients with a positive troponin T (>or=0.01 ng/ml) was not different between the two groups at baseline, it was significantly higher in the placebo-treated group during the final evaluation (p<0.05).
  
  
  CONCLUSIONS
  Serial levosimendan treatments improved left ventricular performance and modulated neurohormonal and immune activation beneficially in patients with advanced heart failure, without increasing myocardial injury.
authors.affiliation: Second Department of Cardiology and Heart Failure Clinic, Attikon University Hospital, Athens, Greece. jparissis@yahoo.com
authors.forename: J T
authors.initials: JT
authors.lastname: Parissis
authors.forename: S
authors.initials: S
authors.lastname: Adamopoulos
authors.forename: D
authors.initials: D
authors.lastname: Farmakis
authors.forename: G
authors.initials: G
authors.lastname: Filippatos
authors.forename: I
authors.initials: I
authors.lastname: Paraskevaidis
authors.forename: F
authors.initials: F
authors.lastname: Panou
authors.forename: E
authors.initials: E
authors.lastname: Iliodromitis
authors.forename: D Th
authors.initials: DT
authors.lastname: Kremastinos
mesh_terms: D000368:Aged; D009202:Cardiomyopathies / Q000209:etiology / Q000276:immunology; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D016207:Cytokines / Q000097:blood; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage*; D007111:Immunity, Cellular / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011724:Pyridazines / Q000008:administration & dosage*; D000077464:Simendan; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood; D014665:Vasodilator Agents / Q000008:administration & dosage*; D018487:Ventricular Dysfunction, Left
chemical_list: D002316:Cardiotonic Agents; D016207:Cytokines; D006835:Hydrazones; D010446:Peptide Fragments; D011724:Pyridazines; D020107:Troponin T; D014665:Vasodilator Agents; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000077464:Simendan