Creatine kinase MB isoforms: a potential predictor of acute cardiac allograft rejection

Abstract

Background: Noninvasive studies to detect or predict acute allograft rejection after heart transplantation have failed to be sufficiently reliable to substitute for endomyocardial biopsy. Isoforms of creatine kinase MB isoenzyme (MB2 and MB1) are extremely sensitive markers of ischemic myocardial damage and, in theory, may be elevated in cardiac allograft rejection when myocardial necrosis is visible on microscopy (International Society for Heart and Lung Transplantation grade 2 or greater).

Methods: We examined, prospectively, the endomyocardial biopsy specimens (n = 256) of 50 consecutive patients undergoing orthotopic heart transplantation. Blood samples for creatine kinase MB isoforms (n = 527) were taken immediately before endomyocardial biopsy and at intervals between biopsies.

Results: The median ratio of MB2/MB1 in plasma samples taken at the time of biopsy for grades 2 and 3 was not significantly different from the ratio from biopsy specimens graded 0 and 1 (1.65 versus 1.33; p = Not significant). The sensitivity for diagnosing a moderately severe rejection was 47% with a specificity of 58%. However, in patients with significant acute rejection (grades 2 and 3) in whom consecutive samples were collected, the MB2/MB1 ratio was significantly increased before histologic changes seen on biopsy in 13 of 16 rejection episodes by a mean of 14 days. The sensitivity for predicting rejection (grade 2 or 3) before endomyocardial biopsy was 60% with a specificity of 71% (positive predictive value 43%, negative predictive value 86%).

Conclusions: Creatine kinase MB isoforms may predict the occurrence of acute rejection before histologic evidence seen on endomyocardial biopsy.