Fulminant acute cellular rejection with negative findings on endomyocardial biopsy

We present a case of a heart transplant recipient who had new-onset heart failure, repeatedly unremarkable endomyocardial biopsies, a negative evaluation for humoral rejection, and subsequently autopsy findings of severe sub-epicardial myocyte necrosis with classic cellular rejection. The sub-endocardial layer was free from rejection. The implications for clinical management, in the context of a diagnosis of "biopsy-negative rejection with hemodynamic compromise," include the need to consider intensification of immunosuppression with regimens similar to those used for biopsy-proven rejection.