Abstract 20890: Change in B-Type Natriuretic Peptide Level Holds Higher Positive Predictive Value Compared to Gene Expression Profiling Test for Cardiac Allograft Rejection
Introduction: BNP levels have been shown to be associated with cardiac rejection, but the predictive value of changes in BNP has not been well-defined. The Allomap gene-expression profiling (GEP) test, owing to its high negative predictive value of 98.9% but relatively low positive predictive value of 4% at a score of >=34, has been suggested as a method to rule-out rejection.
Hypothesis: We assessed the hypothesis that changes in BNP may be equivalent to GEP as a diagnostic test to predict cardiac allograft rejection.
Methods: BNP and biopsy results were obtained for 205 subjects who underwent 4007 endomyocardial biopsy procedures. Biopsies analyzed were more than 180 days post-transplant (median 506 days, IQR 303 – 924 days), with a previous biopsy of grade <=1A. Subjects on dialysis were excluded from the analysis. Our primary outcome was a biopsy with histologic rejection grade >=3A (REJ). We used a repeated measures logistic regression model to assess the association of change in BNP (parameterized categories) with REJ.
Results: There were 53 episodes of REJ in 1544 biopsies analyzed. Median change in BNP (dBNP) for those with REJ was 13.5 pg/mL (IQR -31 to 121 pg/mL) and among those with grade <3A was -3 pg/mL (IQR -34 to 22 pg/mL, Wilcoxon rank-sum p=0.013). dBNP >=250 pg/mL was associated with REJ (OR 11.0, p <0.0001) compared to dBNP of -50 to 50 pg/mL. After adjusting for BMI, absolute BNP value, GFR and time since transplant, dBNP >=250 remained a powerful predictor of REJ (OR 10.3, p<0.0001). A threshold of ΔBNP >=250pg/mL for REJ had a positive predictive value (PPV) of 26% (95% CI 18–34%) and negative predictive value (NPV) of 97% (95% CI 96.6–97.4%). We adjusted our prevalence of REJ (3.4%) to that seen in the CARGO study (1.7%), which changed our PPV to 14% (95% CI 8–21%) and NPV to 98.5% (95% CI 98.2–98.8%).
Conclusions: Change in BNP >=250pg/mL is independently associated with a high risk of Grade >=3A rejection. dBNP <250pg/mL has a high negative predictive value for absence of rejection. Relative to the GEP test, the higher positive predictive value of change in BNP is highly desirable when considering routine surveillance of subjects with a low risk of rejection. This advantage is magnified by the relative cost savings (1/75th the price) compared to the GEP test.
- © 2010 by American Heart Association, Inc.