Are Gene Expression Profile Testing Scores Associated with New Onset Cardiac Allograft Vasculopathy?

Abstract

Purpose Cardiac allograft vasculopathy (CAV) remains a leading cause of death after heart transplantation (HT). Its detection relies on coronary angiography and assessment of maximal intimal thickness (MIT) by intravascular ultrasound (IVUS). Gene Expression Profile (GEP) testing is a non-invasive way to survey rejection post-HT; however, whether it may help detect chronic rejection in the form of CAV is unknown. Methods The AlloMap registry enrolled adult patients > 55 days after HT without allograft dysfunction who underwent GEP testing for rejection surveillance. Eligible patients had no history of significant cellular (ISHLT ≥ 1R) or antibody mediated rejection within 2 months prior to enrollment. CAV was recorded as new onset, stable or progressive by the physician and “no CAV” served as the reference group. When available, MIT by IVUS was compared to median GEP test scores. Samples from patients with more severe CAV (ISHLT Grades 2 and 3) were compared to samples recorded as none or mild CAV (Grade 0 and 1). A linear model was used to assess for differences between groups. Results A total of 12526 samples from 2060 patients were available for analysis. 188 (1.5%) samples were recorded as CAV (106 new onset, 34 progressive and 48 stable disease). New onset CAV was associated with higher median GEP test scores compared to no CAV (31 [IQR 27,34] vs 30 [IQR 26,33], p=0.018) (Figure). Out of 1532 angiography reports available, median GEP test scores were elevated in CAV 2 and 3 (32 [IQR 28,34] compared to CAV 0 and 1 (30 [IQR 26, 33]), p=0.004. There was no correlation between GEP test scores and MIT by IVUS, p=0.089. Conclusion In this registry of low-risk patients post-transplant undergoing GEP testing for rejection surveillance, CAV was seen infrequently. New onset CAV was associated with a higher GEP score however the difference in score was nominal. Future studies are needed to explore whether GEP testing may be used to identify patients at high risk for the development of CAV.