Identification of patients not requiring endomyocardial biopsies late after cardiac transplantation.
BACKGROUND
The risk for rejection is highest early, but graft rejection requiring intensified immunosuppression may be present even late after transplantation. Nonetheless, a considerable number of patients are absolutely free of rejection requiring intensified immunosuppression (Rej) late after transplantation. Therefore, we tried to identify patients who do not need endomyocardial biopsies > or = 2 years after transplantation and those who may benefit from long-term follow-up with routine endomyocardial biopsies.


METHODS
A total of 112 patients (age 45+/-12 years) had a follow-up with regular endomyocardial biopsies of > or = 3 years. A total of 4194 endomyocardial biopsies were performed (1364 > or = 2 years after transplantation). They were divided into three categories: rejection score=0, Texas 0-2 or International Society for Heart and Lung Transplantation (ISHLT) 0 or 1A; rejection score=1, Texas 3-4 or ISHLT 1B or 2; rejection score=2, Texas > or = 5 or ISHLT > or = 3A.


RESULTS
During the third and subsequent posttransplantation years, 31 of 112 (28%) patients had < or = 1 further Rej (total 51). Independent predictors identifying patients with Rej in multivariate analysis were age [odds ratio (OR)=0.96 per year, P<0.05], the sum of rejection score (OR=1.07 per score point, P<0.005) and the mean cyclosporine level in the first 2 years (OR=1.07 per % of upper therapeutic range, P<0.01). Fifty-eight (52%) patients with age >25 years, sum of rejection score < or = 17, and mean cyclosporine level <90th percentile during the first 2 years would not have needed biopsies in the third and subsequent years, whereas the other 48% had a risk of 54% to develop further Rej. In addition to predictors identifying patients with rejection, time after transplantation (OR=0.73 per year, P<0.005), cyclosporine level below therapeutic range (OR=2.15, P<0.05), and reduction of prednisone (OR=2.64, P<0.05) were independent predictors at each endomyocardial biopsy.


CONCLUSIONS
Risk of Rej remained considerably high in approximately one third of our patients late after transplantation. In these, further surveillance biopsies appear justified, whereas half of the patients had no risk of Rej as long as immunosuppressive therapy was sufficient.
Brunner-La Rocca
H P
HP
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Kiowski
W
W
D000017:ABO Blood-Group System; D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D001707:Biopsy, Needle; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000473:pathology*; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors
D000017:ABO Blood-Group System; D007166:Immunosuppressive Agents; D016572:Cyclosporine