Layered Fibrotic Plaques Are the Predominant Component in Cardiac Allograft Vasculopathy: Systematic Findings and Risk Stratification by OCT

Abstract

Objectives The aims of this study were to characterize cardiac allograft vasculopathy (CAV) phenotypes using optical coherence tomography (OCT) and to evaluate the prognostic significance of OCT-determined CAV severity. Background Intravascular OCT enables in vivo characterization of CAV microstructure after heart transplantation. Methods Sixty-two patients undergoing heart transplantation were enrolled at routine angiography from September 2013 through October 2015 and prospectively followed until censoring on May 27, 2016. Optical coherence tomographic acquisitions aimed for the longest possible pull-backs, including proximal segments of all 3 major vessels. Plaques and bright spots were analyzed by delineating circumferential borders and measuring the angulation of total circumference. Layers were contoured for absolute and relative estimates. Nonfatal CAV progression (NFCP) during follow-up was registered. NFCP included occluded vessels or severe (≥70%) new angiographic coronary stenosis or percutaneous coronary intervention. Results A total of 172 vessels were categorized as follows: no CAV, n = 111; mild to moderate CAV (<70% stenosis), n = 40; and severe CAV (≥70% stenosis), n = 21. Layered fibrotic plaque (LFP) was the most prevalent plaque component, and the extent increased with angiographic CAV severity (p < 0.01). During follow-up, 22 of 172 vessels (13%) experienced NFCP. Median follow-up was 633 days (interquartile range: 432 to 808 days). The extent of LFP (hazard ratio: 5.0; 95% confidence interval: 2.1 to 12.4; p < 0.0001) and the extent of bright spots (hazard ratio: 6.2; 95% confidence interval: 2.4 to 15.8, p < 0.001) were strong predictors of NFCP. By combining LFP and bright spots, a strong NFCP predictive model was obtained (hazard ratio: 8.9; 95% confidence interval: 2.6 to 29.9; p < 0.0001). Conclusions OCT enables the detection of CAV-associated plaque compositions and allows early detection and differentiation of vessel wall disease not visible on angiography. LFP was the most prevalent plaque component, was strongly associated with NFCP, and may be associated with stepwise CAV progression caused by organizing mural thrombi. (The GRAFT Study: Evaluation of Graft Function, Rejection and Cardiac Allograft Vasculopathy in First Heart Transplant Recipients; NCT02077764)