Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes.
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.
Division of Cardiology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA 90095-6988, USA.
Grace W
GW
Wu
Jon A
JA
Kobashigawa
Michael C
MC
Fishbein
Jignesh K
JK
Patel
Michelle M
MM
Kittleson
Elaine F
EF
Reed
Krista K
KK
Kiyosaki
Abbas
A
Ardehali
D000206:Actuarial Analysis; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D001706:Biopsy; D002196:Capillaries / Q000276:immunology / Q000473:pathology; D015935:Complement C4b; D003324:Coronary Artery Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology; D004699:Endocardium / Q000276:immunology / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006333:Heart Failure / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007518:Isoantibodies / Q000097:blood*; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood; D011183:Postoperative Complications / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D018487:Ventricular Dysfunction, Left / Q000276:immunology / Q000473:pathology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015935:Complement C4b; D007518:Isoantibodies; D010446:Peptide Fragments; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C032261:complement C4d