Pathology of chronic cardiac rejection: An analysis of the epicardial and intramyocardial coronary arteries and myocardial alterations in 43 human allografts.
Forty-three cardiac allografts (39 autopsies and 4 surgically resected hearts) showing chronic rejection-defined as greater than 75% narrowing of one or more major coronary arteries (MCA) with or without severe narrowing of intramyocardial coronary arteries (ICA)-were studied histologically. MCA showed purely concentric narrowing in 24 patients (56%), and 19 patients (44%) showed eccentric narrowing in some arteries. Fibrofatty (collipid) plaques were seen in 54%, abundant foam cells sans free lipid in 33%, purely fibrous plaques in 14%, and calcification in 9%. Four pathologic alterations separated graft atherosclerosis from usual atherosclerosis: (i) the presence in the MCA and/or ICA of either active or healed vasculitis, (ii) outer medial defects attributable to mediolysis and/or foam cell transformation in the MCA, (iii) the diffuse nature of the atherosclerotic-like changes, and (iv) obliterative narrowing of the ICA. No difference was found between early and late survivors with regard to features of graft atherosclerosis. The majority of the patients studied had received steroid-based immunosuppression. MCA and/or ICA active vasculitis was observed in the absence of acute myocardial rejection in some patients. ICA showed intimal thickening in 37% of patients, active vasculitis in 21%, healed vasculitis in 7%, and combination of the latter two changes in 12%. Acute myocardial ischemia, present in 33 hearts (77%), had the following distribution: subendocardial in 42%, focal in 36%, and regional transmural in 21%. Myocytolysis (83%), coagulative necrosis (26%), and contraction band necrosis (16%) were noted. Replacement fibrosis of the myocardium was frequently observed (44%), followed by interstitial (33%) and perivascular fibrosis (1%). Patients with chronic rejection showed no difference with regard to the incidence and severity of rejection episodes during life compared with patients without chronic rejection.