Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes

J Heart Lung Transplant. 2009 May;28(5):417-22. doi: 10.1016/j.healun.2009.01.015. Epub 2009 Mar 14.

Abstract

Background: Antibody-mediated rejection (AMR) has been associated with poor outcome after heart transplantation. The diagnosis of AMR usually includes endomyocardial biopsy findings of endothelial cell swelling, intravascular macrophages, C4d+ staining, and associated left ventricular dysfunction. The significance of AMR findings in biopsy specimens of asymptomatic heart transplant patients (normal cardiac function and no symptoms of heart failure) is unclear.

Methods: Between July 1997 and September 2001, AMR was found in the biopsy specimens of 43 patients. Patients were divided into 2 groups: asymptomatic AMR (AsAMR, n = 21) and treated AMR (TxAMR with associated left ventricular dysfunction, n = 22). For comparison, a control group of 86 contemporaneous patients, without AMR, was matched for age, gender, and time from transplant. Outcomes included 5-year actuarial survival and development of cardiac allograft vasculopathy (CAV). Patients were considered to have AMR if they had > or = 1 endomyocardial biopsy specimen positive for AMR.

Results: The 5-year actuarial survival for the AsAMR (86%), TxAMR (68%), and control groups (79%) was not significantly different (p = 0.41). Five-year freedom from CAV (> or = 30% stenosis in any vessel) was AsAMR, 52%; TxAMR, 68%; and control, 79%. Individually, freedom from CAV was significantly lower in the AsAMR group compared with the control group (p = 0.02). There was no significant difference between AsAMR vs TxAMR and TxAMR vs control for CAV.

Conclusions: Despite comparable 5-year survival with controls after heart transplantation, AsAMR rejection is associated with a greater risk of CAV. Trials to treat AsAMR to alter outcome are warranted.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actuarial Analysis
  • Adult
  • Aged
  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • Biopsy
  • Capillaries / immunology
  • Capillaries / pathology
  • Complement C4b
  • Coronary Artery Disease / immunology
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / pathology
  • Coronary Vessels / immunology
  • Coronary Vessels / pathology
  • Endocardium / immunology
  • Endocardium / pathology
  • Female
  • Graft Rejection / immunology*
  • Graft Rejection / mortality
  • Graft Rejection / pathology
  • Heart Failure / immunology
  • Heart Failure / pathology
  • Heart Transplantation / immunology*
  • Heart Transplantation / mortality
  • Heart Transplantation / pathology
  • Humans
  • Immunoenzyme Techniques
  • Isoantibodies / blood*
  • Macrophages / immunology
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Myocardium / immunology
  • Myocardium / pathology
  • Peptide Fragments / blood
  • Postoperative Complications / immunology*
  • Postoperative Complications / mortality
  • Postoperative Complications / pathology
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Ventricular Dysfunction, Left / immunology
  • Ventricular Dysfunction, Left / pathology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Isoantibodies
  • Peptide Fragments
  • Complement C4b
  • complement C4d