Endomyocardial biopsies (EMBs) are routinely used to detect cardiac allograft rejection after heart transplantation (HTx), but they are invasive and costly. Serial changes in brain natriuretic peptide (BNP) levels may serve as a non-invasive marker of rejection in HTx recipients. However, the value of BNP monitoring is unclear, particularly early after transplant. We sought to evaluate the relationship between intra-individual changes in BNP levels and cardiac allograft rejection during the first 180 days following HTx.

Methods: This retrospective study included adults (18-70 years) who underwent primary HTx at the University of Colorado between January 2010 and September 2014. BNP levels, EMB results, and clinical data were abstracted from medical records. For each BNP level (log-transformed), the change from median logBNP up to that time point was calculated for each patient. The primary outcome was moderate-to-severe cardiac allograft rejection, as defined by an EMB with either ISHLT Grade ≥ 2R/3A cellular rejection or pathological antibody-mediated rejection (Grade ≥ pAMR 2). Mixed effects logistic regression included change from median logBNP, age at transplant, BMI, and eGFR as independent variables (fixed effects), as well as a random intercept for each patient.

Results: The cohort consisted of 78 HTx recipients (71% men, 82% Caucasian, 56% non-ischemic cardiomyopathy). Mean (± SD) age, BMI, and eGFR were 50 ± 13 years, 26 ± 5 kg/m², and 76 ± 27 mL/min/1.73 m², respectively. The analysis included 567 EMBs, 567 BNP levels, and 28 episodes of moderate-to-severe rejection. The median BNP in patients with versus without a history of moderate-to-severe rejection was 450 pg/ml (IQR, 153-836 pg/ml) versus 275 pg/ml (IQR, 147-550 pg/ml). In multivariate logistic regression, change from median logBNP (p=0.036) and BMI (p=0.04) were significantly associated with moderate-to-severe rejection, with odds ratios of 1.64 (95% CI, 1.03-2.61) and 0.88 (95% CI, 0.79-0.995), respectively.

Conclusions: Intra-individual changes in BNP levels were a significant predictor of moderate-to-severe rejection in the first 180 days post-HTx, although the effect was modest. Larger studies, evaluating multiple observations per patient, are needed to examine the utility of BNP monitoring for the prediction of acute rejection early after HTx.

CITATION INFORMATION: Dann J, Deininger K, Reinhold D, Page II R, Ambardekar A, Lindenfeld J, Aquilante C. Relationship Between Changes in Brain Natriuretic Peptide Levels and Cardiac Allograft Rejection Early After Heart Transplantation. Am J Transplant. 2016;16 (suppl 3).

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