Role of vascular remodeling in the pathogenesis of early transplant coronary artery disease: A multicenter prospective intravascular ultrasound study

Background: Luminal narrowing in transplant coronary artery disease is thought to be primarily caused by intimal proliferation, and the role of vascular remodeling is less certain. Methods and Results: We studied cardiac allografts from 83 prospectively recruited patients immediately and 1 year after transplant using intravascular ultrasound in a multicenter study. We measured coronary artery dimensions in 310 angiographically matched segments (175 were also fully matched by ultrasound criteria). At 1 year, lumen area changed by -1.8 +/- 3.7 mm(2) (p < 0.0001, 14% of baseline lumen area). Thirty-three percent of this luminal loss was due to intimal thickening and 67% to vessel shrinkage. Shrinkage also occurred (-0.9 <plus/minus> 3.2 mm(2), 7% of baseline total area) in segments free of detectable intimal disease at baseline and at 1 year. Using the mean baseline total vessel area (13.9 mm(2)) as the cutoff, we divided the cohort into the large and the small coronary-segment groups. The large-segment group (n = 176) shrank more (-2.6 +/- 4.4 vs -0.03 +/- 2.8 mm(2), p < 0.0001), but intimal growth was similar in both groups (0.8 <plus/minus> 2.2 vs 0.4 +/- 1.3 mm(2), p = not significant). Analysis of the 175 fully ultrasound matched sub-cohort showed similar results. Changes in intimal area, total vessel area, and lumen area were similar in segments with (n = 132) and segments without (n = 178) pre-existing donor disease. Despite overall shrinkage, change in total vessel area positively correlated with change in intimal area (r = 0.29, p < 0.0001). Conclusion: In large coronary segments, coronary artery shrinkage plays an important role in the loss of luminal diameter early after cardiac transplantation, whereas new intimal growth occurs in both large and small segments. Pre-existent donor disease does not aggravate these processes. Compensatory remodeling with increasing intimal growth retards the rate of lumen loss. As is intimal thickening, shrinkage and compensatory remodeling are important pathogenic mechanisms in transplant coronary artery disease.