Mary Ripple

Comparison of Necropsy Findings in Patients With Sarcoidosis Dying Suddenly from Cardiac Sarcoidosis Versus Dying Suddenly from Other Causes

The clinical diagnosis of cardiac sarcoidosis can be difficult and is largely dependent on newer imaging modalities. A retrospective search of sudden cardiac deaths was performed from a reference laboratory and statewide medical examiner system for a 12-year period. Planimetry was performed on gross photographs of transverse short-axis sections, and the phase of the lesion and the portion of myocardium extent was estimated histologically. Lesions were classified histologically as early (primarily lymphocytic), intermediate (primarily granulomatous), and late (primarily scar). A total of 41 cases were found, including 25 in which the death was ascribed to sarcoidosis of the heart (group 1) and 16 in which sudden death was due to other findings (group 2). No significant differences were found in age or activity at death, although gross scars and epicardial nodules were more frequent in group 1 (p <0.0001). In the hearts with gross scars, the ventricular septum had the largest percentage of involvement (32%) followed by the posterior wall (25%). Histologically, the intermediate phase predominated in group 1, and the late phase predominated in group 2. Approximately 50% of the cases in group 1 had involvement in the right ventricular apex and septum, suggesting a positive yield by biopsy. In conclusion, cardiac sarcoidosis causing sudden death is characterized by extensive active granulomas with a predilection for the subepicardium and ventricular septum.

Monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques

BackgroundMyeloperoxidase (MPO) -containing macrophages and neutrophils have been described at sites of plaque rupture. The presence of these cells in precursor lesions to acute rupture (thin cap atheroma, or vulnerable plaque) and within thrombi adjacent to ruptures has not been described, nor an association with iron-containing macrophages within unstable plaques.MethodsWe studied 61 acute ruptures, 15 organizing ruptures, 31 thin cap fibroatheromas, and 28 fibroatheromas from 72 sudden coronary death victims by immunohistochemical and histochemical techniques. Inflammatory cells were typed with anti-CD68 (macrophages), anti-BP-30 (neutrophil bactericidal glycoprotein), and anti-MPO. Iron was localized by Mallorys Prussian blue stain. In selected plaques alpha smooth muscle actin (DAKO, Carpinteria, CA, clone M0851) was performed.ResultsMPO positive cells were present in 79% of ruptured caps, 28% of thin cap fibroatheroma, and no fibroatheromas; neutrophils were present in 72% of ruptures, 8% of thin cap fibroatheromas, and no fibroatheromas. Iron containing foam cells were present in the caps of 93% of acute ruptures, of 85% of organizing ruptures, 20% of thin cap atheromas, and 10% of fibroatheromas. MPO positive cells were more frequent in occlusive than non-occlusive thrombi adjacent to ruptures (p = .006) and were more numerous in diabetics compared to non-diabetics (p = .002)ConclusionUnstable fibrous caps are more likely to contain MPO-positive cells, neutrophils, and iron-containing macrophages than fibrous caps of stable fibroatheromas. MPO-positive cells in thrombi adjacent to disrupted plaques are associated with occlusive thrombi and are more numerous in diabetic patients.

Adventitial lymphocytic inflammation in human coronary arteries with intimal atherosclerosis.

BACKGROUND The relationship between adventitial inflammation, plaque type, and culprit plaque morphology in the epicardial arterial circulation has not been studied in detail. METHODS We studied semiserial sections of coronary arteries at autopsy from patients dying with severe coronary disease, 81 men (age 50 + or - 12 years) and 13 women (age 52 + or - 13 years). Lesions were classified at 3- to 5-mm segments according to modified AHA criteria. Adventitial lymphocyte aggregates were assessed at every 5-mm interval and graded semiquantitatively. Macrophage density in the adventitial fat and intima was assessed with anti-CD68 staining. RESULTS Adventitial lymphocytic inflammation increased with percent stenosis (P<.0001) and not calcification (P>.2). Hemorrhage into late core, rupture, erosion, and thin caps all had greater adventitial lymphocytic inflammation independent of percent stenosis (P<.0001). Peri-adventitial adipose macrophage density was increased in plaques with atheromas (206 + or - 22 mm(2) vs. 121 + or - 15 mm(2) in fibrous plaques; P=.02) and correlated positively with adventitial lymphocytes (P<.0001) and intimal macrophage content (P<.0001). CONCLUSIONS Features associated with plaque instability are associated with significantly greater degrees of adventitial lymphocytic inflammation, both as lymphocyte aggregates and as adipocyte-derived macrophages. Further study is required to determine the nature of the association between intimal and adventitial lymphocytic inflammation.

Immunolocalisation of fibrin in coronary atherosclerosis: implications for necrotic core development

Background: Intraplaque haemorrhage has been shown to be important in necrotic core enlargement. Immunolocalisation of fibrin within progressive stages of plaque progression has not been extensively studied. Methods: Histological sections (n = 74) of human coronary arteries were stained immunohistochemically for fibrin II, red blood cell antigen (glycophorin A), and CD31. Plaques were chosen to represent a range of lesions [6 adaptive intimal thickening, AIT (AHA grade I); 4 intimal xanthomas (AHA grade II), 19 pathologic intimal thickening, PIT (AHA grade III, or pre‐atheroma); 34 fibroatheromas, FA (AHA grade IV and V); and 11 thin cap fibroatheromas (TCFA, AHA grade IV)]. Results: Fibrin was generally absent in the intima of AIT and PIT, with moderate staining in cores of early FA (2.6 ± 0.3). All late FA and TCFA demonstrated intracore fibrin, with mean scores of 2.9 ± 0.3 and 3.0 ± 0.3, respectively. Intimal vasa vasorum counts increased with intimal fibrin score (p < 0.0001); in 68% of cores with fibrin staining, there was minimal or no evidence of red cell breakdown. Conclusions: Fibrin in necrotic cores is present proportional to intraplaque vasa vasorum and before red cells, suggesting leakage of vessels before frank intraplaque haemorrhage. Fibrin may play a role in the bridge between pre‐atheroma and atheroma.

Sudden coronary death caused by pathologic intimal thickening without atheromatous plaque formation

BACKGROUND Atherosclerotic plaques progress from early lesions with little free cholesterol and lipid to late fibroatheromas with necrotic cores that may rupture. The frequency of severe coronary atherosclerosis without core formation in any artery in sudden coronary death is not known. METHODS We studied 314 hearts from 253 men and 61 women who died suddenly from severe coronary stenosis (≥ 1 epicardial artery with ≥ 75% luminal area narrowing) and with no other cause of death. If no section demonstrated any necrotic core, the designation was nonatheromatous atherosclerosis; if there was ≥ 1 necrotic core, the designation was atheromatous atherosclerosis. Plaques were scored for the presence of calcification, intimal inflammation, and neovasculature on a 5-point scale. Plaque burden was estimated semiquantitatively. RESULTS In 22 men (9%) and 14 women (23%), there were no necrotic cores in any plaque (nonatheromatous atherosclerosis). Fourteen of these 36 nonatheromatous atherosclerosis cases had focal acute thrombus due to erosion (39%). Of the remaining 278 cases (atheromatous atherosclerosis), acute erosions were present in 25 (9%; P<.0001). Sudden death due to nonatheromatous atherosclerosis occurred more frequently in women (P<.001), in Blacks (20%; P=.003), and at a younger age (44± 12 years) than atheromatous atherosclerosis (52 ± 12 years; P=.0003). On multivariate analysis, nonatheromatous atherosclerosis was associated with younger age (P=.001), female gender (P=.004), and Black race (P=.006). CONCLUSIONS Nonatheromatous atherosclerosis constitutes slightly >10% of sudden coronary deaths and is more frequent in young Black women. Nonatheromatous atherosclerosis is a relatively infrequent pathway for coronary plaque progression, leading to severe disease and sudden death that may involve plaque erosion.

Diabetic ketoacidosis: a silent death.

AbstractDiabetic ketoacidosis (DKA) results from severe insulin deficiency and can be diagnosed at autopsy despite no known history of the disease. Diabetic ketoacidosis may be the initial manifestation of type 1 diabetes or may result from increased insulin requirement in type 1 diabetic patients. The purpose of this study was to determine the percentage of DKA death investigated by the Office of Chief Medical Examiner that was not associated with a known history of diabetes.Cases investigated by the Office of Chief Medical Examiner during a 6-year period whose cause of death was DKA were identified using a centralized database. To determine the percentage with known history of diabetes, investigation reports were reviewed for any documentation of this history. The toxicology reports of all DKA deaths were reviewed together with histologic slides, if available, for possible microscopic changes. Concentrations of vitreous glucose, vitreous acetone, and blood acetone were used to diagnose DKA in these autopsied cases.Nearly a third of all death from DKA (32 of 92 during a 6-year period) occurred in individuals who had no known history of diabetes, emphasizing the importance of regular physicals that include a check of glucose concentration, and especially if any warning signs are present. In a case of sudden death, it is recommended that the volatile toxicology analysis at a medical examiner’s office should include tests for acetone concentration, which when elevated, together with an elevated vitreous glucose, indicates DKA.

Morphologic Features of Exertional Versus Nonexertional Sudden Death in Patients With Hypertrophic Cardiomyopathy

Pathologic features that characterize hypertrophic cardiomyopathy (HC) in exertional versus nonexertional sudden deaths have not been extensively studied. We performed gross measurements and histologic analysis on 103 autopsy cases of HC and correlated these with clinical findings. Pathologic features of the 71 sudden deaths were compared between exertional and nonexertional deaths. Age at death was significantly younger in exertional (27 +/- 13 years) versus nonexertional sudden deaths (40 +/- 16 years, p = 0.0003). Exertional deaths were more likely in women (35 of 37) versus sudden deaths at rest (21 of 34, p = 0.0002). There was no significant difference in the incidence of syncope in the exertional sudden deaths (14%) compared to the nonexertional sudden deaths (9%, p = 0.5) or in the rate of a previous diagnosis of HC (21% vs 21%, respectively). Mean heart weight was significantly decreased in exertional sudden deaths versus nonexertional sudden deaths. There was no difference in the frequency of left ventricular outflow tract plaque (54% exertional vs 46% nonexertional, p = 0.06). By multivariate analysis, including all categories of HC, only decreased heart weight (p = 0.02) and male gender (p = 0.002) were significantly associated with exertional sudden death. In conclusion, there are no pathologic features that would identify patients with HC at risk for exertional death. Because relatively decreased heart weight is strongly associated with exertional death, and because a large proportion of exertional deaths with HC are not associated with significant asymmetry, cardiologists should be careful in excluding the diagnosis of HC in athletes with even mild degrees of cardiomegaly, especially young men.

Morphologic characteristic of coronary artery disease, with emphasis on thromboses, in patients younger than 40 years of age.

There are few pathologic descriptions of fatal coronary artery disease in the young. The morphologic characteristics of sudden coronary deaths in 47 hearts from patients younger than 40 years were studied. Numbers of plaques with necrotic cores were quantitated in each heart. Compared to 194 sudden coronary deaths >40 years, heart weight was lower, acute plaque erosions more frequent, and extent of disease less in the ≤40 years group. Plaque burden was less in hearts with erosions, and healed infarcts more common in hearts with stable plaque. The numbers of fibroatheromas increased with age until the 6th decade (P < .0001) as well as the proportion of total plaques that were atheromatous. Plaques in younger patients have fewer lipid-rich cores. Most thrombi show areas of organization, with layering frequent in erosions, suggesting a possible method of plaque enlargement in the absence of necrotic core formation.