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). METHODS AND 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.
journal_name
Circulationjournal_title
Circulationauthors
Gullestad L,Ueland T,Fjeld JG,Holt E,Gundersen T,Breivik K,Følling M,Hodt A,Skårdal R,Kjekshus J,Andreassen A,Kjekshus E,Wergeland R,Yndestad A,Frøland SS,Semb AG,Aukrust Pdoi
10.1161/CIRCULATIONAHA.105.564971subject
Has Abstractpub_date
2005-11-29 00:00:00pages
3408-14issue
22eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.105.564971journal_volume
112pub_type
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