Low AlloSure® in HeartCare® Associated with Low Risk of Significant Allograft Rejection: An Analysis of SHORE

Abstract

<h3>Purpose</h3> HeartCare is a non-invasive method of surveillance for cardiac allograft rejection comprised of gene expression profiling (AlloMap, AM) and donor derived cell-free DNA (AlloSure-Heart, AS). AM scores inform immune quiescence whereas AS reflects presence of tissue injury. <h3>Methods</h3> Surveillance HeartCare Outcomes Registry (SHORE) is a multicenter, observational registry assessing the clinical utility of AS/AM. AM score >30 (<6 months) or > 34 (≥6 months) was deemed positive (AM+). AS result >0.15% was defined as positive (AS+). The presence of acute cellular rejection ≥2R or antibody mediated rejection (AMR 1, 2, or 3) was assessed at 14 and 30 days following AS/AM. <h3>Results</h3> Of the 4927 samples analyzed, 2507 (50.9%) were concordant low AS and AM (AS-/AM-), 558 (11.3%) were AS+/AM+. Discordance was noted in 1245 (25.3%) with AS+/AM- and 617 (12.5%) with AS-/AM+. The AS+/AM+ cohort had significantly more rejection events when compared with the AS-/AM- group at 14 days (1.25% vs 0.4%, p = 0.032) with a trend toward more rejection at 30 days (1.61% vs 0.68%, p = 0.055). The AS-/AM+ group had fewer rejection episodes when compared with those with AS+/AM+ at 30 days (0.16% vs 1.61%, p = 0.017) with a trend toward fewer rejection events at 14 days (0.16% vs 1.25%, p = 0.055). The AS-/AM- group had the fewest number of endomyocardial biopsies performed when compared to all other cohorts at 14 days (p < 0.05). <h3>Conclusion</h3> AS/AM provides complementary information regarding probability of clinically significant allograft rejection. In those with discordant AM and AS results, presence of a low AS was associated with lower risk of rejection in the subsequent 14 and 30 days. A concordantly low AS and AM may safely obviate a surveillance endomyocardial biopsy in the appropriately selected.