Vascular remodeling 1 year after cardiac transplantation.
BACKGROUND
The belief that vascular remodeling and intimal hyperplasia are causes of luminal narrowing in cardiac allograft vasculopathy (CAV) is controversial. This study evaluated the relationship of vascular remodeling and intimal hyperplasia to luminal narrowing 1 year after orthotopic heart transplantation.


METHODS
Intravascular ultrasound imaging was performed on 190 cardiac transplant recipients at baseline and again 1 year after transplantation as part of a randomized trial of mycophenolate mofetil (MMF) and azathioprine (Aza). Studies 1 year apart were matched at 625 sites. All sites were classified into positive, non-significant and negative remodeling patterns, depending on a change of +/-10% in external elastic membrane area. Of the 190 patients, 99 were randomized to receive MMF, and 91 to receive Aza.


RESULTS
A total of 625 sites were observed. Of these, 52% had no remodeling, 25% exhibited vessel dilation, and 23% had vessel shrinkage in the presence of variable intimal growth (Delta intimal area: 0.73 +/- 1.70 mm2, p < 0.0001; 1.23 +/- 2.02 mm2, p < 0.0001; and 0.20 +/- 1.40 mm2, p = 0.09, respectively). Sixty percent of the lumen loss was due to a decrease in external elastic membrane area and 40% to an increase in intimal area (p = 0.005). Compared with Aza-treated patients, the MMF-treated patients had a lower incidence of vessel shrinkage (17% vs 28%, p = 0.001), and a trend for smaller maximum intimal thickness (0.21 +/- 0.25 mm vs 0.29 +/- 0.31 mm, p = 0.052).


CONCLUSIONS
Positive remodeling is associated with intimal growth, but negative remodeling does not correlate with any specific change in intimal hyperplasia. Constrictive remodeling is more responsible than intimal hyperplasia for the luminal narrowing that occurs. MMF is more efficacious than azathioprine in preventing the development of CAV at 1 year, by reducing the degree and incidence of vessel shrinkage and the progression of intimal hyperplasia.
Li
Haiyan
H
Department of Medicine, Division of Cardiology, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA.
Tanaka
Koji
K
Chhabra
Ankush
A
Oeser
Brandy
B
Kobashigawa
Jon A
JA
Tobis
Jonathan M
JM
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D003331:Coronary Vessels / Q000000981:diagnostic imaging*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000000981:diagnostic imaging / Q000517:prevention & control; D016027:Heart Transplantation / Q000000981:diagnostic imaging*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011379:Prognosis; D017539:Tunica Intima / Q000000981:diagnostic imaging; D018084:Ultrasonography, Interventional
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine