The effect of etanercept on cardiac transplant recipients: a study of TNFalpha antagonism and cardiac allograft hypertrophy.
Cardiac allograft hypertrophy is associated with persistent expression of cardiac tumor necrosis factor (TNF)-alpha. We investigated whether TNFalpha antagonism would impact allograft hypertrophy. EFECT (EFfect of Etanercept on Cardiac Transplantation) was a randomized, controlled, double-blind trial evaluating the effect of etanercept versus placebo treatment immediately posttransplant. The primary end-point was change in left ventricular (LV) mass after 6 months. Secondary endpoints included degree of collagen deposition at 6 months and incidence of adverse events. Forty-nine patients were randomized to either etanercept or placebo. LV mass increased significantly in both arms at 6 months, with a smaller increase in the etanercept group (19% vs. 33%, P=ns). Myocardial collagen content increased in the placebo, but not the etanercept, group (+39.8%, P<0.08 vs. -7.0%, P=NS). Allograft hypertrophy develops posttransplant with a corresponding increase in extracellular matrix. Etanercept appeared to decrease LV hypertrophy by decreasing extracellular matrix deposition.
Torre-Amione
Guillermo
G
Methodist DeBakey Heart Center, Houston, TX, USA. gtorre@tmh.tmc.edu
Wallace
Cynthia K
CK
Young
James B
JB
Koerner
Michael M
MM
Thohan
Vinay
V
McRee
Susan
S
Bogaev
Roberta C
RC
D003094:Collagen / Q000378:metabolism; D004311:Double-Blind Method; D000068800:Etanercept; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D000068800:Etanercept