title: Effect of thalidomide on cardiac remodeling in chronic heart failure: results of a double-blind, placebo-controlled study.
abstract: BACKGROUND
  Inflammation and matrix degradation may play a pathogenic role in chronic heart failure (CHF), and therefore, we examined whether thalidomide, a drug with potential immunomodulating and matrix-stabilizing properties, could improve left ventricular (LV) function in patients with CHF secondary to idiopathic dilated cardiomyopathy (IDCM) or coronary artery disease (CAD).
  
  
  RESULTS
  Fifty-six patients with CHF and an LV ejection fraction (LVEF) <40% who were already on optimal conventional cardiovascular treatment were randomized to thalidomide (25 mg QD increasing to 200 mg QD) or placebo and followed up for 12 weeks. Our main findings were as follows: (1) During thalidomide treatment but not during placebo, there was a marked increase in LVEF (&7 EF units) along with a significant decrease in LV end-diastolic volume and heart rate. (2) This improvement in LVEF was accompanied by a decrease in matrix metalloproteinase-2 without any changes in its endogenous tissue inhibitor, suggesting a matrix-stabilizing net effect. (3) Thalidomide also induced a decrease in total neutrophil count and an increase in plasma levels of tumor necrosis factor-alpha, suggesting both proinflammatory and antiinflammatory effects. (4) The effect of thalidomide on LVEF was more marked in IDCM than in CAD, possibly partly reflecting that the former group was able to tolerate a higher thalidomide dosage.
  
  
  CONCLUSIONS
  Although our results must be confirmed in larger studies that also examine the effects on morbidity and mortality, our findings suggest a role for thalidomide in the management of CHF in addition to traditional cardiovascular medications.
authors.affiliation: Department of Cardiology, Rikshospitalet, 0027 Oslo, Norway. lars.gullestad@medisin.uio.no
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Jan G
authors.initials: JG
authors.lastname: Fjeld
authors.forename: Even
authors.initials: E
authors.lastname: Holt
authors.forename: Torstein
authors.initials: T
authors.lastname: Gundersen
authors.forename: Kjell
authors.initials: K
authors.lastname: Breivik
authors.forename: Magne
authors.initials: M
authors.lastname: Følling
authors.forename: Anders
authors.initials: A
authors.lastname: Hodt
authors.forename: Rita
authors.initials: R
authors.lastname: Skårdal
authors.forename: John
authors.initials: J
authors.lastname: Kjekshus
authors.forename: Arne
authors.initials: A
authors.lastname: Andreassen
authors.forename: Elin
authors.initials: E
authors.lastname: Kjekshus
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Wergeland
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Stig S
authors.initials: SS
authors.lastname: Frøland
authors.forename: Anne Grete
authors.initials: AG
authors.lastname: Semb
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007107:Immune System / Q000187:drug effects; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D010919:Placebos; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy
chemical_list: D016209:Interleukin-8; D010919:Placebos; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D020778:Matrix Metalloproteinase 2