This study was designed to investigate tissue characterization of the coronary allograft atherosclerotic plaque with virtual histology intravascular ultrasound (VH-IVUS) imaging to assess the presence and predictors of vessel wall inflammation and its significance in cardiac allograft vasculopathy (CAV) progression. A unique form of accelerated atherosclerosis, CAV remains the leading cause of late morbidity and mortality in heart transplant patients. The pathogenesis of CAV is not fully elucidated. A total of 86 patients with coronary allograft vasculopathy underwent VH-IVUS examination of the left anterior descending coronary artery 3.61 +/- 3.04 years following cardiac transplantation. Based on the VH-IVUS plaque characteristics, coronary allograft plaque was divided on virtual histology intravascular ultrasound-derived "inflammatory" (VHD-IP) (necrotic core and dense calcium > or =30%) and "noninflammatory" plaque (VHD-NIP) (necrotic core and dense calcium <30%). Total rejection scores were calculated based on the 2004 International Society of Heart and Lung Transplantation rejection grading system. In the whole study population, the mean percentage of fibrous, fibrofatty, dense calcified, and necrotic core plaques in a mean length of 62.3 +/- 17.4 mm of the left anterior descending coronary artery were 50 +/- 17%, 16 +/- 11%, 15 +/- 11%, and 18 +/- 9%, respectively. Patients with a 6-month total rejection score >0.3 had significantly higher incidence of VHD-IP than those with a 6-month total rejection score < or =0.3 (69% vs. 33%, p = 0.011). The presence of VHD-IP at baseline was associated with a significant increase in plaque volume (2.42 +/- 1.78 mm(3)/mm vs. -0.11 +/- 1.65 mm(3)/mm, p = 0.010), plaque index (7 +/- 9% vs. 0 +/- 8%, p = 0.04), and remodeling index (1.24 +/- 0.44 vs. 1.09 +/- 0.36, p = 0.030) during 12 months of follow-up when compared with the presence of VHD-NIP at baseline and during follow-up. The presence of VHD-IP as assessed by VH-IVUS is associated with early recurrent rejection and with higher subsequent progression of CAV. A VH-IVUS assessment may add important information in the evaluation of transplant recipients.