Evaluation of biopsy classification for rejection: relation to detection of myocardial damage by monoclonal antimyosin antibody imaging.
OBJECTIVE
This study sought to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global estimate of myocardial transplant-related cardiac damage detected by myocardial uptake of monoclonal antimyosin antibodies.


BACKGROUND
The diagnosis and treatment of acute cardiac allograft rejection is based on the interpretation of endomyocardial biopsies. Because allograft rejection is a multifocal process and biopsy is obtained from a small area of the right ventricle, sampling error may occur. Global assessment of myocardial damage associated with graft rejection is now possible with the use of antimyosin scintigraphy. The present study was undertaken to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global assessment of transplant-related myocardial damage detected by antimyosin scintigraphy.


METHODS
Biopsies (n=395) from 112 patients were independently interpreted by three pathologists in a blinded manner according to the original Stanford four-grade (normal, mild, moderate and severe) and the current International Society of Heart and Lung Transplantation (ISHLT) seven-grade (0, 1A, 1B, 2, 3A, 3B and 4) classifications. The results were correlated with 395 antimyosin studies performed at the time of the biopsies. The heart/lung ratio of antimyosin antibody uptake was used to assess the severity of myocardial damage.


RESULTS
In the Stanford biopsy grade classification, significantly higher antimyosin uptake, indicating increasing degrees of myocardial damage, were associated with normal (1.78+/-0.26), mild (1.88+/-0.31) and moderate (1.95+/-0.38) biopsy classifications for rejection (p < 0.01). In the ISHLT classification, significant differences were detected only for antimyosin uptake associated with grades 0 (1.77+/-0.26) and 3A (1.98+/-0.39) but not for intermediate scores (1A, 1B and 2). In view of the similar intensity of antibody uptake among the various grades, ISHLT biopsy scores were regrouped: normal biopsies in grade A; 1A and 1B as grade B; and 2 and 3A as grade C. Antimyosin uptake in grades A, B and C was 1.78+/-0.26, 1.88+/-0.31, 1.95+/-0.38, respectively (p < 0.01).


CONCLUSIONS
The current ISHLT seven-grade scoring system does not reflect the progressive severity of myocardial damage associated with heart transplant rejection. Because myocardial damage constitutes the basis of treatment for allograft rejection, there is a need to reevaluate the ISHLT grading system, given its importance for multicenter trials.
Ballester
M
M
Department of Pathology, Hospital Sant Pau, Barcelona, Spain. ballester.tiana@teleline.es
Bordes
R
R
Tazelaar
H D
HD
Carrió
I
I
Marrugat
J
J
Narula
J
J
Billingham
M E
ME
D000911:Antibodies, Monoclonal; D001706:Biopsy; D006084:Graft Rejection / Q000000981:diagnostic imaging / Q000473:pathology*; D006321:Heart / Q000000981:diagnostic imaging; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D007205:Indium Radioisotopes; D009206:Myocardium / Q000473:pathology*; D009218:Myosins / Q000276:immunology*; D009336:Necrosis; D015588:Observer Variation; D009942:Organometallic Compounds; D016719:Radioimmunodetection
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D009942:Organometallic Compounds; C058899:imciromab pentetate; D009218:Myosins