Abstract 14045: Increased Fibrosis and Microvessel Disease in Allograft Endomyocardial Biopsies of Children With Chronic Graft Failure Due to Cardiac Allograft Vasculopathy

Abstract

Introduction: The pathogenesis of chronic graft failure (CGF) in pediatric heart transplant recipients (PHT) is multifactorial and includes cardiac allograft vasculopathy (CAV). Prior research has shown that CGF can present as microvessel disease (MVD) and fibrosis on endomyocardial biopsies (EMB), however, optimal routine surveillance is not established. We analyzed EMB specimens to establish histopathologic findings of CGF represented by PHT with CAV. Hypothesis: PHT recipients with CGF secondary to CAV have increased fibrosis and MVD on EMB. Method: We performed a retrospective case-control study. PHT with moderate to severe (M-S) CAV diagnosed on cardiac catheterization between 2017-2020 were identified. EMB from time of M-S CAV diagnosis (CAV-EMB) was reviewed (excluding those with significant intercurrent rejection) and compared to their EMB prior to any CAV diagnosis (pre-CAV-EMB) and controls that were matched for age at and time since transplant (Tx) . Fibrosis was qualitatively graded on a scale of 0-5 and MVD was scored as number of capillaries with stenotic wall thickening (due to either endothelial cell swelling or medial hypertrophy) per fields of view. Results: Eight PHT with CAV-EMB and pre-CAV-EMB and 8 controls were identified. CAV-EMB group was 2.5 years (IQR: 0.9,8.0) old at time of Tx and 10.6 years post-Tx (8.3,15.5) at EMB. Pre-CAV-EMB was 1.8 years (1.1,2.8) prior to CAV-EMB. In the CAV, pre-CAV, and control groups median fibrosis score was 3.0 (2.0, 3.0) vs 2.0 (2.0, 3.0) vs 1.0 (0, 1.0) (p= 0.001) and MVD score was 2.1 (1.3, 2.9) vs 2.0 (1.6, 2.8) vs 0.5 (0.2, 0.7), respectively (p= 0.007). These were significantly different between pre-CAV-EMB vs controls (fibrosis p=0.003, MVD p=0.007) and CAV-EMB vs controls (fibrosis p=0.001, MVD p=0.005), but not between pre-CAV-EMB vs CAV-EMB. Furthermore, fibrosis and MVD scores were strongly correlated (r=0.78, p<0.001). Conclusion: Histopathological evidence of increased fibrosis and MVD is noted in EMB with CGF secondary to CAV and these findings pre-date angiographic CAV diagnosis. Further studies in larger PHT cohorts are needed to assess time course of fibrosis and MVD to improve surveillance of CAV and CGF.