In the aorta ulceration and thrombosis were characteristic of plaques with a high proportion of their volume occupied by extracellular lipid, and in which there was a shift toward a preponderance of monocyte/macrophages compared with smooth muscle cells in the cap.

Objective-To determine the role of healed plaque disruption in the generation of chronic high grade coronary stenosis. Methods-Coronary arteries obtained at necropsy were perfuse fixed with formal saline for 24 hours at 100 mg Hg. The percentage lumen diameter stenosis was measured in each 3 mm segment containing a plaque, using the lumen size at the nearest histologically normal segment as the reference point. Each segment was prepared for histological examination and stained with Sirius red and immunohistochemistry for smooth muscle actin. Healed disruption was considered to be present when under polarised light there was a break in the yellow-white dense collagen of the cap filled in by more loosely arranged green collagen. Increased smooth muscle density in the green staining areas was required. Each section was read independently by two observers; any segment with discordant views was considered negative. Material-31 men aged 51-69 dying suddenly of ischaemic heart disease. 39 coronary arteries were studied containing 256 separate plaques, after excluding coronary arteries with old total occlusions, an acute culprit thrombotic lesion, diVuse disease without normal arterial segments, and arteries related to old myocardial scars. Results-16 of 99 plaques causing < 20% diameter stenosis had prior disruption. In the 21-50% stenosis range 16 of 86 plaques showed healed disruption. Stenosis > 51% by diameter was present in 71 plaques, 52 of which showed a healed disruption pattern. The diVerence between stenosis < 50% and stenosis > 51% was significant by the 2 test (p < 0.001). Conclusions-Subclinical episodes of plaque disruption followed by healing are a stimulus to plaque growth that occurs suddenly and is a major factor in causing chronic high grade coronary stenosis. This mechanism would explain the phasic rather than linear progression of coronary disease observed in angiograms carried out annually in patients with chronic ischaemic heart disease. (Heart 1999;82:265-268)

Background. Immunization with cardiac myosin induces experimental autoimmune heart disease in genetically predisposed mice. These mice produce heart-specific autoantibodies, some of which are directed against the cardiac myosin isoform.Methods and Results. We have reported the presence of circulating heart-specific autoantibodies in 26% of patients with idiopathic dilated cardiomyopathy (DCM) using indirect immunofluorescence. To identify the autoantigen(s) recognized by heart-specific autoantibodies in human disease, we tested, by Western blotting, sera from 26 DCM patients, 14 of whom were cardiac antibody-positive and 12 antibody-negative, as well as sera from 12 patients with cardiac failure from ischemic or valvular heart disease and from 13 normal subjects who were cardiac antibody-negative. Crude myofibrillar proteins and myosin preparations extracted from human atrial or ventricular specimens were used as antigens. Sodium dodecyl sulfate polyacrylamide gel electrophoresis was performed. The proteins were electrophoretically transferred to nitrocellulose sheets. The paper strips were incubated in sera from patients or controls at 1:100 dilution; the reaction was revealed with a peroxidase-labeled second antibody against human immunoglobulin. Twelve of the 14 DCM sera (86%) containing heart-specific antibodies reacted with both the a-(atrial specific) and ,B-(ventricular and slow skeletal) myosin heavy chain isoforms; none of the