A clinical correlation study of severity of antibody-mediated rejection and cardiovascular mortality in heart transplantation.
BACKGROUND
The current International Society for Heart and Lung Transplantation (ISHLT) diagnostic criteria for antibody-mediated rejection (AMR) designate AMR as either absent (AMR 0) or present (AMR 1), without grading its severity. Yet, the extent of histologic and immunofluorescence (IF) findings of AMR varies across endomyocardial biopsies (EMBs). In this study, we hypothesized that the severity of AMR, as assessed on EMBs, correlates with cardiovascular mortality in heart transplant recipients.


METHODS
All EMBs from 1985 to 2005 were evaluated. Biopsy specimens were uniformly studied by light microscopy and IF early post-transplant. A comprehensive vascular score (V1: no AMR, to V5: severe AMR) was prospectively assigned to each EMB, based on severity of both histologic and IF findings. Univariate Cox proportional hazards regressions were performed using indicators of vascular scores alone, combined, and cumulatively.


RESULTS
Nine hundred six patients were transplanted and included in the study. Mean age was 46.6 +/- 15.5 years and 82% were male. A total of 26,236 EMBs comprised the study data. As expected, histologic and immunopathologic findings of AMR varied in severity. An incremental risk of cardiovascular mortality was found with more severe AMR whether vascular scores were analyzed individually (p = 0.001), in combination (p = 0.01) or cumulatively (p = 0.006).


CONCLUSIONS
The severity of AMR on EMBs correlates with an incremental cardiovascular mortality risk after heart transplantation, suggesting that AMR should be viewed as a spectrum rather than just as present or absent. Supplementing the ISHLT AMR diagnostic guidelines with a consensus severity scale is warranted.
Kfoury
Abdallah G
AG
Intermountain Medical Center and Intermountain Healthcare, Utah, USA. akfoury@imail.org
Renlund
Dale G
DG
Snow
Gregory L
GL
Stehlik
Josef
J
Folsom
Jan W
JW
Fisher
Patrick W
PW
Reid
Bruce B
BB
Clayson
Stephen E
SE
Gilbert
Edward M
EM
Everitt
Melanie D
MD
Bader
Feras M
FM
Singhal
Arun K
AK
Hammond
M Elizabeth H
ME
D000328:Adult; D001706:Biopsy; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000503:physiopathology; D005260:Female; D006084:Graft Rejection / Q000401:mortality / Q000503:physiopathology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D014589:Utah / Q000453:epidemiology
D007518:Isoantibodies