Role of endomyocardial biopsy in the diagnosis of chronic rejection in human heart transplantation

To assess the pathologic findings observed in the setting of post-transplant graft atherosclerosis, we have studied 18 endomyocardial biopsies (EMB) from 18 heart-transplanted patients collected at the same time that a coronary angiography (CA) showed changes consistent with graft atherosclerosis. Twenty-two EMB from patients with heart transplant with normal CA were used as controls. In spite of the small size of the sample, the number of acute rejection (AR) episodes correlated with the appearance of graft atherosclerosis (p < 0.001). Heart biopsies in graft atherosclerosis showed myointimal proliferation, thickening and folding of the wall of precapillary arteries, myocyte hypertrophy, and interstitial and perivascular fibrosis. Type III and type IV collagen, laminin, and fibronectin were increased in areas of interstitial and perivascular fibrosis, as well as in the vessel's wall. Fibronectin accumulation was more evident in the subendothelium and inner media of affected vessels. These changes were never found all together in control biopsies. Even though the inespecificity of some of those findings, we conclude that chronic graft atherosclerosis in a heart transplant may be suspected by endomyocardial biopsy when most of these alterations are seen together, especially if small precapillary arteries are present in the specimen.