Biopsy-Negative Rejection: a Rare but Difficult Issue in Heart Transplantation

Purpose of Review: Biopsy-negative rejection is a condition defined by a cardiac dysfunction with a left ventricular ejection fraction (LVEF) ≤ 45% with normal histology and with the absence of other causes of cardiac allograft damage. The purpose of this review is to determine the incidence of biopsy-negative rejection, the therapeutics, and the outcome in the light of new techniques of evaluation or detection of acute rejection in heart-transplanted patients. Although rare, many physicians have once experienced this difficult situation. Even though it is considered the gold standard for the diagnosis of rejection, pathology is of limited help in biopsy-negative rejection by definition. Recent Findings: Showed advances made in the field of transplant medicine, such as cardiovascular magnetic resonance imaging, noninvasive biomarkers, and molecular assessment using transcriptomic analysis of the cardiac allograft tissue on endomyocardial biopsies. Summary: Biopsy-negative rejection marks the limit of histology; new techniques developed to improve the follow-up of heart transplant recipients could be of future help in the understanding of biopsy-negative rejection and maybe dethrone the biopsy for the diagnostic of acute rejection. © 2018, Springer Nature Switzerland AG.