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 thou ght to be primarily caused by intimal proliferation, and the role of vascul ar remodeling is less certain. Methods and Results: We studied cardiac allografts from 83 prospectively re cruited patients immediately and 1 year after transplant using intravascula r ultrasound in a multicenter study. We measured coronary artery dimensions in 310 angiographically matched segments (175 were also fully matched by u ltrasound 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 lumina l 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. Usin g the mean baseline total vessel area (13.9 mm(2)) as the cutoff, we divide d the cohort into the large and the small coronary-segment groups. The larg e-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/minu s> 2.2 vs 0.4 +/- 1.3 mm(2), p = not significant). Analysis of the 175 full y 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 ove rall shrinkage, change in total vessel area positively correlated with chan ge 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 transpla ntation, whereas new intimal growth occurs in both large and small segments . Pre-existent donor disease does not aggravate these processes. Compensato ry remodeling with increasing intimal growth retards the rate of lumen loss . As is intimal thickening, shrinkage and compensatory remodeling are impor tant pathogenic mechanisms in transplant coronary artery disease.