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 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 (Delta Ii) and maximal intimal thickness [Delta Mt] of 46 matched coronary segments between initial and 1-year follow-up studies. Coronary segments with endothelial dysfunction (constriction greater than or equal to 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) (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 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.