Does Allosure Scoring Rise in the Setting of Cytomegalovirus (cmv)? A Case Series

Abstract

Introduction Currently under investigation, HeartCare® surveillance combines both AlloMap® (immune activity mRNA) and Allosure ® (graft cell free DNA) data and is purported to be a comprehensive method of assessing cellular and antibody mediated graft rejection in the orthotopic heart transplant (OHT) patient population. Prior literature suggests that increased Allomap® scores are observed in setting of Cytomegalovirus (CMV) viremia, which is one of the most common infections following transplantation. Furthermore, decreased scoring trends have also been reported once the once viremia is resolved. The likely mechanism has been thought to be immune activation/modulation of one or more of the 11 genes in the Gene Expression Profiling (GEP) signature. To date there is a paucity of data supporting this phenomenon occurring in tangent with Allosure® use. Methods Herein is a retrospective review of two heart transplant recipients that had HeartCare and CMV surveillance. CMV donor/ recipient data, graft assessment via echocardiograms, biopsy data, Beta natriuretic peptide (BNP) trends, and presence of human leukocyte antigens (HLA) were also analyzed. Results Patient #1 is a 57 y/o Caucasian male status post OHT 9/2019 due to ischemic cardiomyopathy (ICM), CMV Recipient+/Donor- (R+/D-), with normal left and right ventricular (LV and RV), and Ejection Fraction (EF) 50%. Biopsy History #1: 1R, p AMR0, #2 1R, pAMR0. Mild elevations in BNP (peak 127) throughout viremia course, negative DSA Class I or Class II. Patient #2 is a 57 y/o Hispanic male status post OHT 9/9/2019 due to ICM, CMV R+/D+ with normal LV and RV and EF 50% as of 5/2020. Biopsy History #1: 1R, pAMR0 #2: 0R, pAMR0. Mild BNP elevations throughout viremia course (peak 147), negative DSA Class I and Class II. Discussion Based on prior studies, CMV infection can trigger allograft rejection/acute rejection thus triggering CMV reactivation. Our case series describes CMV viral load increased as did increased HeartCare® values, in the absence of graft dysfunction and rejection. This observation underscores the importance of simultaneous rejection and infection monitoring to guide clinical treatment. Although Allosure® rise was diagnostically subtle, trend surveillance is critical to avoid overtreatment and repeat cardiac biopsies.