Biopsy-Negative Rejection Late after Heart Transplantation: Impact on Long-Term Outcome

Purpose Biopsy-negative rejection (BNR) is an entity where the endomyocardial biopsy (EMB) shows no findings of rejection, but there is proven cardiac dysfunction i.e. low echocardiographic left ventricular ejection fraction or abnormal cardiac hemodynamics. BNR has been noted both early and late after heart transplantation (HTx). It has been reported that late biopsy-proven acute rejection (both cellular and antibody rejection) has been associated with worse outcome. It is not known whether late BNR is associated with long-term adverse outcomes. Methods Between 2008 and 2013, we assessed 33 HTx patients who developed BNR via the following criteria: ACR≤1R, AMR 0, cardiac dysfunction (LVEF≤40%, CI Results Late BNR was associated with significantly reduced subsequent 5-year survival and an increase in the development of angiographic CAV compared to those with early BNR. The timing of BNR did not make a difference in the development of NF-MACE. (see Table) Conclusion Late BNR in HTx is associated with poor long-term outcome. The mechanism of this rejection is not clear but represents a heightened immune response that is being missed on EMB. More aggressive augmentation of immunosuppression and/or immunomodulation are indicated in patients presenting with late BNR.