(Circulation. 1996;93:457-462.)
© 1996 American Heart Association, Inc.
Articles |
Early Endothelial Dysfunction Predicts the Development of Transplant Coronary Artery Disease at 1 Year Posttransplant
From the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Stacy F. Davis, MD, Brigham and Women's Hospital, Cardiovascular Division, 75 Francis St, Boston, MA 02115.
Background Accelerated coronary arteriosclerosis is the major obstacle to long-term survival after cardiac transplantation. Endothelial dysfunction is common early posttransplant. The relationship between early endothelial dysfunction and the development of allograft arteriosclerosis has not been analyzed serially with intravascular ultrasound in the same patients. We hypothesized that an early constrictor response to acetylcholine, indicative of endothelial dysfunction, may predict the development of transplant coronary arteriosclerosis.
Methods and
Results Endothelium-dependent
vasomotion was assessed early posttransplant in 20 patients by serial
intracoronary acetylcholine infusion, and the percent
change in diameter was measured by quantitative angiography. The
development of arteriosclerosis was studied by use
of intravascular ultrasound in the same 20 patients by quantifying the
changes in intimal index (
Ii) and maximal intimal thickness
[Mt] of 46 matched coronary segments between initial and
1-year follow-up studies. Coronary segments with
endothelial dysfunction (constriction 
5%; n=23)
demonstrated a significantly greater increase in mean Ii and Mt by 1
year posttransplant compared with segments with normal
endothelial function (n=23) (Ii=7±2% versus
2±1%
[P<.05] and Mt=140±40 versus
50±20 µm
[P<.05]). No other parameters examined
predicted the development of allograft
arteriosclerosis in the initial year
posttransplant.
Conclusions Paired studies that used intravascular ultrasound showed that early endothelial dysfunction predicts the development of allograft arteriosclerosis during the initial year posttransplant. This early pathophysiological feature is likely an important marker that could be useful in therapeutic trials.
Key Words: endothelium • acetylcholine • ultrasonics • transplantation • atherosclerosis
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