Lumen loss in transplant coronary artery disease is a biphasic process involving early intimal thickening and late constrictive remodeling: Results from a 5-year serial intravascular ultrasound study

Background - Coronary artery disease is the major cause of late cardiac allograft failure. However, few data exist regarding the natural history of changes in intimal and external elastic membrane (EEM) areas after heart transplantation. Methods and Results - In 38 transplant recipients, serial intravascular ultrasound examinations were performed 3.7±2.2 weeks after transplantation and annually thereafter for 5 years. In 59 coronary arteries, we compared 135 matched segments among serial studies, in each segment, intravascular ultrasound images were digitized at 1-nun intervals, and mean values of EEM and lumen and intimal areas were analyzed. In the first year after transplantation, the intimal area increased significantly from 1.8+ 1.6 to 3.0+2.1 mm² (P<0.001). Subsequently, the annual increase in intimal area decreased. EEM area did not change during the first year; however, between years 1 and 3, significant expansion of EEM area occurred (15.4±4.6 to 17.2±5.4 mm², P<0.001). Thereafter, EEM area decreased significantly from 17.2±5.4 mm² (year 3) to 15.1±4.9 mm² (year 5, P=0.01). Different mechanisms of lumen loss were observed during 2 phases after transplantation: early lumen loss primarily caused by intimal thickening and late lumen loss caused by EEM area constriction. Conclusions - This serial ultrasound study revealed that most of the intimal thickening occurred during the first year after heart transplantation. Changes in the EEM area showed a biphasic response, consisting of early expansion and late constriction. Thus, different mechanisms of lumen loss were observed during the early and late phases after transplantation.