Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes

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.

Figures

Figure 1

Endomyocardial biopsy findings in antibody-mediated rejection. (A) Prominent intravascular cells are present in the myocardium in the absence of lymphoid cellular infiltrate (hematoxylin and eosin [H&E]; original magnification ×200). (B) Magnification of panel A at ×400 (H&E). (C) Prominence of macrophages amongst the cells with a CD68 immunoperoxidase stain (original magnification ×400). (D) Presence of only rare T lymphocytes with CD3 immunoperoxidase stain (original magnification ×400); (E) Highlighting of endothelial cells and confirmation of the macrophages’ intravascular location with the CD34 immunoperoxidase stain (original magnification ×400). (F) Deposition of C4d complement component in capillaries with the C4d immunoperoxidase stain (original magnification ×400). From: Fishbein and Kobashigawa: Current Opin. Cardiol 2004;19:166. Reprinted with permission of Wolters Kluwer.

Figure 2

There was no significant difference in 5-year actuarial survival among the patients with asymptomatic antibody-mediated rejection (AsAMR), treated antibody-mediated rejection (TxAMR), and control patients.

Figure 3

The 5-year freedom from cardiac allograft vasculopathy was lower in the treated antibody-mediated rejection (TxAMR) and asymptomatic antibody-mediated rejection (AsAMR) groups compared with the control group. Cardiac allograft vasculopathy is defined as ≥ 30% stenosis in any vessel on an angiogram.