[Pathology of heart transplantation.(Morphological study of 1246 endomyocardial biopsies from 167 transplanted hearts). Causes of early, intermediate, and late deaths].

From January 1988 through October 1997, 167 cardiac transplants were performed. 1246 endomyocardial biopsies (EMBs) from 138 cardiac allograft recipients were investigated and graded according to the Working Formulation (WF) criteria. The specimens were inadequate in 44 EMBs (3.5%), while 598 (48%) showed no rejection. The grade of rejection was: mild (grade 1A and 1B) in 531 EMBs (42.6%), mild/moderate (grade 2) in 38 (3.1%), and moderate (grade 3A and 3B) in 35 (2.8%). The indications for transplantation were: dilated cardiomyopathy (46.1%); ischemic disease (37.1%); valvular disease (12%); hypertrophic cardiomyopathy (1.8%); myocarditis (1.2%); congenital cardiopathy (0.6%), restrictive cardiomyopathy (0.6%) and chronic rejection (0.6%). The most reliable histologic feature of acute rejection was the myocyte necrosis or damage in presence of pironinophilic mononuclear cell infiltrate, so our protocol requires multifocal or diffuse myocyte damage (rejection grade 3A and 3B) to perform an additional treatment, which was required in 35 cases (2.8%). An intermediate grade mild/moderate 2, was introduced from the WF to classify the EMBs in which the myocyte necrosis was scant or not clear; this grade in our series generally resolves without any additional treatment; in order to monitor the rejection another EMB was performed 5 days after in these patients. The EMBs showed also the following lesions other than acute rejection: Quilty A (79 patients; 57.25%), Quilty B (24 pts; 17.39%), early ischemic necrosis (43 pts; 31.15%) and late ischemic necrosis (5 pz; 3.62%). Quilty B and late ischemic necrosis were correlated with acute rejection (grade 2), furthermore the patients with graft vascular disease showed 3 or more episodes of acute rejection. These findings confirm the relationship between acute and chronic rejection. Furthermore, a relationship between chronic rejection (4 pts) and infection from hepatitis C (antibodies positive 3 pts/4) and cytomegalovirus (antibodies positive 4 pts/4) was found in our series. In the follow-up period (117 months), a 30.72% death rate was recorded; the main causes of death were: early failure of the transplanted heart (30 pts) in 4 of them associated with pulmonary hypertension, infections (6 pts), sudden death (4 pts), graft's vasculopathy (4 pts), acute pancreatitis (1 pts) pulmonary embolism (1 pts), lung (1 pts) and ovary (1 pts) carcinoma, acute rejection (1 pts), others (2 pts). In the early period (< 1 month), the most frequent cause of death was the early failure of the transplanted heart, while in the late period (> 1 year) the chronic rejection following by sudden death and tumours. The actuarial survival curve drops to 83.13% after the first post-operative month, abates to 75.30 at the end of the first year, and progressively decreases to 70.48% at the end of the fifth follow-up year. The mortality rate was 38.7% in pts transplanted for ischemic disease and 24.7% for dilated cardiomyopathy. Cardioplegia seems to play an important role in the success of the heart transplant.