Secondary Logo

Institutional members access full text with Ovid®

Biopsy-negative cardiac transplant rejection: etiology, diagnosis, and therapy

Fishbein, Michael C.a; Kobashigawa, Jonb

Current Opinion in Cardiology: March 2004 - Volume 19 - Issue 2 - p 166-169
Heart transplantation

Purpose of review As the frequency of cellular rejection after heart transplantation is decreasing, biopsy-negative episodes of rejection are being recognized more often. This article reviews the features of humoral rejection, which we believe is responsible for most episodes of biopsy-negative rejection. Hemodynamic compromise, in the absence of acute cellular rejection, called biopsy-negative rejection occurs in 10 to 20% of cardiac allograft recipients. These episodes of rejection are often more severe, and more difficult to treat, than classical acute cellular rejection. Histologic, immunofluorescence, and immunoperoxidase studies of endomyocardial biopsies from such patients often reveal intravascular macrophages, and immunoglobulin and complement deposition in capillaries, in the absence of lymphoid infiltrates, suggesting an antibody-mediated or humoral form of rejection.

Recent findings Humoral rejection is associated with increased graft loss, accelerated transplant coronary artery disease, and increased mortality. Severely ill patients require intense therapy, which includes high-dose corticosteroids, cytolytic agents, intravenous heparin, intravenous gamma globulin, plasmapheresis, and/or antiproliferative agents.

Summary Currently, our knowledge of the pathogenesis, diagnostic criteria, and optimal therapy for biopsy-negative rejection is incomplete, and evolving.

aDepartments of Pathology and Laboratory Medicine and bMedicine, The David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Correspondence to Michael C. Fishbein, MD, Professor of Pathology and Medicine, Department of Pathology and Laboratory Medicine, Room A7-149, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA

Tel: 310 825 9731; fax: 310 794 4161; e-mail:

© 2004 Lippincott Williams & Wilkins, Inc.