EARLY ENDOTHELIAL DYSFUNCTION PREDICTS THE DEVELOPMENT OF TRANSPLANT CORONARY-ARTERY DISEASE AT 1 YEAR POSTTRANSPLANT

Background Accelerated coronary arteriosclerosis is the major obstacle to long-term survival after cardiac transplantation. Endothelial dysf unction is common early posttransplant. The relationship between early endothelial dysfunction and the development of allograft arterioscler osis has not been analyzed serially with intravascular ultrasound in t he same patients. We hypothesized that an early constrictor response t o acetylcholine, indicative of endothelial dysfunction, may predict th e development of transplant coronary arteriosclerosis. Methods and Res ults Endothelium-dependent vasomotion was assessed early posttransplan t in 20 patients by serial intracoronary acetylcholine infusion, and t he percent change in diameter was measured by quantitative angiography . The development of arteriosclerosis was studied by use of intravascu lar ultrasound in the same 20 patients by quantifying the changes in i ntimal index (Delta Ii) and maximal intimal thickness [Delta Mt] of 46 matched coronary segments between initial and 1-year follow-up studie s. Coronary segments with endothelial dysfunction (constriction greate r than or equal to 5%; n=23) demonstrated a significantly greater incr ease in mean Ii and Mt by 1 year posttransplant compared with segments with normal endothelial function (n=23) (Delta Ii=7+/-2% versus 2+/-1 % [P<.05] and Delta Mt=140+/-40 versus 50+/-20 mu m [P<.05]). No other parameters examined predicted the development of allograft arterioscl erosis in the initial year posttransplant. Conclusions Paired studies that used intravascular ultrasound showed that early endothelial dysfu nction predicts the development of allograft arteriosclerosis during t he initial year posttransplant. This early pathophysiological feature is likely an important marker that could be useful in therapeutic tria ls.