The morphologic spectrum of dilated cardiomyopathy and its relation to immune-response genes

Endomyocardial biopsies from 174 patients with dilated cardiomyopathy (DC) were examined. Eight patients with histologically proven myocarditis were excluded from the study. A peculiar pattern of oversized and bizarre nuclei was observed in only some of the remaining patients. Two groups were identified: those with and without this feature (groups A and B, respectively). Myocyte width, nuclear diameter and nuclear/sarcoplasmic ratio were significantly higher in group A. The mean respective values were 36 [+ or -] 5 [mu], 14 [+ or -] 3 [mu] and 0.41 [+ or -] 0.08 for group A versus 20 [+ or -] [mu], 7 [+ or -] 2 [mu] and 0.37 [+ or -] 0.08 for group B. interstitial fibrosis was similarly present in groups A and B. Endocardial thickness was significantly increased in all patients, with group A showing the highest mean value. The morphologic features showed no correlation with the clinical condition of the patients at time of presentation. HLA typing was performed in 50 consecutive patients, 38 from group A and 12 from group B. DR4 and DR5 antigens were significantly more frequent in DC patients than in a normal population control (400 blood donors), while DR3 was less frequent. Group A was more strongly associated with the DR5 antigen than group B (55.3 vs 25.0%, respectively). it was less strongly associated with the DR4 antigen compared with group B (21.5 vs 41.7%, respectively). No difference was observed between the 2 groups concerning negative association with the DR3 antigen. Endemyocardial biopsies from DC patients reveal marked morphologic changes from patient to patient. The histopathologic identification of 2 distinct DC groups with different HLA marker associations suggests that immune-response genetic factors may play a role in the histopathologic expression of the disease. (Am J Cardiol 1989;64:991-995)
Dilated cardiomyopathy (DC) is a disease of the heart muscle in which the muscle cells (myocytes) degenerate and fibrous elements invade the tissue causing the wall to thicken. Genetic factors have been suggested as one possible cause. In particular, the association of specific human leukocyte antigens (HLA), molecules present on the surface of blood cells of every individual, with DC has been proposed. Fifty out of 166 patients diagnosed with DC on the basis of cardiac biopsy also provided blood samples for HLA determination. Biopsies were evaluated using the light microscope and measurements were of myocyte width (average width of the heart cell), various cell nuclei dimensions including diameter, extent of fibrosis (or presence of fibrous tissue), thickness of the heart wall, and other related variables. Blood from 400 hundred healthy blood donors was used to determine HLA antigen frequencies in the general population for comparison with the group with DC. The most important finding regarding muscle cells from DC patients was the presence of very large, abnormal cell nuclei. The magnitude of these changes, however, was not correlated with extent of symptoms or duration of the disease. The 60 percent of patients who had this abnormality constituted Group A, while the remainder made up Group B. When DC patients were compared with the population as a whole, they were found to display HLA antigen subtypes DR4 and DR5 more often, with no difference for DR3. Among DC patients as a group, HLA antigen subtype DR4 was more frequent in Group B than Group A; subtype DR5, on the other hand, was more frequent in Group A patients. The lack of correlation between abnormal cells and disease progression argued against interpreting these changes as a pathological response to failure of the heart's contracting mechanism, since they should then be more numerous in advanced disease. The cell nuclei abnormalities resembled changes noted during activation of protein synthetic machinery. Analysis of HLA subtypes showed that a type of cellular damage can be associated with an HLA subtype. This finding is consistent with the hypothesis that DC is one of several diseases caused by the chemical product of an interaction between a virus and the immune system. The hypothesis holds that this product then becomes toxic to the body's cells. While implications of these results for treatment or progression of DC are not clear, clarification of the role of the immune system with respect to this disease could shed light on its etiology. (Consumer Summary produced by Reliance Medical Information, Inc.)