Inflammatory Burden of Cardiac Allograft Coronary Atherosclerotic Plaque Is Associated With Early Recurrent Cellular Rejection and Predicts a Higher Risk of Vasculopathy Progression

Objectives: 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. Background: 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. Methods: 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 ≥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. Results: 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 ≤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 mm³/mm vs. -0.11 ± 1.65 mm³/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. Conclusions: 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.