Abstract 2312: Limitations of Molecular Expression Profiling (Allomap Score) in Predicting Endomyocardial Biopsy Findings in Cardiac Allograft Recipients: Two Year Follow-Up Surveillance Study
Background: Molecular profiling of immune pathways implicated in cardiac allograft rejection has led to the development of a composite score (Allomap, range: 0 – 40) recently approved for clinical use. The potential for non-invasive monitoring in lieu of invasive biopsies and its reported high negative (NPV) predictive value are offset by low positive predictive value (PPV) and controversy about the threshold score (≥ 30 vs. ≥ 35) consistent with rejection. Nevertheless, the score has not been extensively validated in clinical practice.
Methods: We obtained blood samples from cardiac allograft recipients (n=242 samples over 2 years) for determination of Allomap8 score at the time of endomyocardial biopsy. We excluded patients with recent transplant, on high dose steroids or recently treated for rejection. Pathologists blinded to AlloMap score interpreted all biopsies.
Results: The mean Allomap score in the entire cohort was 29.9±0.4 (median: 31). The distribution was non-Gaussian with the majority of samples in the upper quartile [< 24: n=43 (18 %), 25–29: n=49 (20%), 30 –34: n=98 (40 %), > 35: n=52 (22 %)] Only 9 biopsy specimens (3.7%) were consistent with severe rejection (ISHLT 3A/3B or ≥ 2R per amended classification). Scores were not significantly different across the spectrum of ISHLT grades. Allomap scores of non-rejectors (ISHLT 0), mild rejectors (1-R) and significant rejectors (≥ 2R) were not significantly different (29.3±0.6 vs. 30.2±0.5 vs. 30.1±2.2, respectively). In predicting clinically significant (ISHLT ≥ 3A or 2-R) rejection, the NPV of Allomap was 95 %, yet PPV was < 10 %. Sensitivity (30 –55%) and specificity (37–78%) were highly dependent on the threshold used (≥30 vs. ≥35), thus ROC performance was suboptimal.
Conclusions: Although molecular profiling of candidate genes to predict cardiac allograft rejection remains an attractive, non-invasive and physiologically sound concept, the clinical application of the present assay is still limited