Cases Of Sudden Coronary Death Research Articles

Application of OCT in the Forensic Pathological Diagnosis of Coronary Artery Atherosclerosis and Myocardial Infarction.

To investigate the value of optical coherence tomography （OCT） in the diagnosis of coronary atherosclerosis and myocardial infarction in forensic identification. OCT and hematoxylin-eosin （HE） examination were performed to examine the pathological samples of coronary artery and myocardial infarction in 5 cases of sudden coronary death. The morphological and local measurement indexes were compared. In the OCT images, the layers of coronary artery could be distinguishably featured, and the atheroma plaques had a good morphological correspondence with HE slices. The normal myocardia in the OCT image showed weak light signals with high absorbance, while the fiber scar tissues in the myocardial infarction areas showed strong light signals with low absorbance. There were no significant differences on the fibrous cap thickness in coronary atherosclerotic plaques or intima-media thickness between the OCT images and the HE slices （P>0.05）. In the OCT images, the optical densities of the old myocardial infarction areas （1 226.24±622.66） and those of normal myocardia （3 707.90±962.98） were significantly different （ P<0.05）. The OCT image has a good morphological consistency with HE slice, thus is expected to be the primary screening method for the forensic pathology examination of coronary artery atherosclerosis and myocardial infarction, which can help to improve the diagnostic accuracy.

Validity of plasma remnant lipoproteins as surrogate markers of antemortem level in cases of sudden coronary death

Hitherto triglycerides (TG) and TG-rich lipoproteins were been of limited value as surrogates for antemortem levels. We measured TG levels in postmortem plasma from sudden coronary death cases (SCD, n=91) by using two TG assays, Dry Chem TG (free glycerol was added) and the Determiner L-TG (without added free glycerol) that measured net TG. TG levels were markedly higher by the Dry Chem TG ( y) vs. Determiner L-TG ( x), y=1.03 x+229 mg/dl. HPLC showed large amounts of free glycerol in postmortem plasma and in TG-rich lipoprotein remnants (RLP). These results were verified in a rabbit model of SCD. Further, RLP from SCD were found to be biophysically similar to those from living patients with coronary artery disease (CAD). In conclusion, postmortem plasma sampled up to 12 h after death is appropriate for measuring lipid and lipoproteins, TG and RLP-TG as surrogates for antemortem levels when a TG assay without added free glycerol is used.

Coronary atherosclerosis in unheralded sudden coronary death under age 50: histo-pathologic comparison with ‘healthy’ subjects dying out of hospital

Aim: sudden coronary death (SCD) in older individuals is generally associated with extensive coronary atherosclerosis, although it may be the first manifestation of ischaemic heart disease. In younger age-groups, SCD may occur in the presence of less severe disease. We sought to (1) examine the extent of coronary atherosclerosis in young victims of SCD compared with age- and sex-matched controls, (2) analyse the composition of atherosclerotic plaques in these patients, (3) identify the predominant mechanism of SCD, and (4) evaluate the possibility of detecting this mechanism on the basis of morphologic plaque features, in particular presence and amount of lipid accumulation and calcific deposits. Methods and results: coronary arteries were obtained at autopsy from 28 victims of SCD under age 50 with no prior clinical manifestation of ischaemic heart disease (IHD) and no myocardial scar formation and from 16 age- and sex-matched subjects dying of noncardiac causes out of hospital. Sections of all available major coronary arteries were cut in 5-mm intervals to yield a total of 1357 histologic sections, which were analysed using digitised planimetry. Victims of SCD had significantly more major coronary arteries per subject with luminal area narrowing ≥75% than controls (on average, 2.1 vs. 0.2). Plaque area per histologic section was 5.1±2.1 mm 2 in SCD cases and 2.0±0.9 mm 2 in controls ( P<0.001). The major constituent of all plaques was fibrous tissue. Lipid core area per section was 0.49±0.59 mm 2 in SCD cases and 0.004±0.01 mm 2 in controls ( P<0.001), and calcified plaque area was 0.18±0.19 mm 2 in SCD cases and 0.02±0.05 mm 2 in controls ( P<0.001), both defining significant differences between SCD cases and controls. Arterial thrombosis, most often with underlying plaque rupture was the mechanism of SCD in >80% of the cases. Considering histologic sections with ≥50 and with ≥75% area stenosis, plaque rupture was independently predicted by lipid core area. Calcific deposits were a frequent feature of plaque rupture but were only associated with it in univariate analysis. Conclusions: the extent and severity of coronary atherosclerosis in young victims of SCD as the first manifestation of IHD was substantially greater than in age-and sex-matched controls and comparable with that previously reported in SCD cases with a broader age range. Lipid core and calcified plaque areas provided for excellent separation between the two groups, which may have implications for identifying persons at increased risk for SCD by non invasive visualisation and assessment of the coronary arteries.

Effect of menopause on plaque morphologic characteristics in coronary atherosclerosis

Background Coronary artery disease in women appears 10 to 15 years later than in men. To test the hypothesis that the effects of estrogen may manifest themselves as histologic differences in coronary plaques, we examined the hearts of premenopausal and postmenopausal women who died suddenly from coronary artery disease. Methods We studied 51 cases of sudden coronary death and 47 deaths in women who died from noncoronary causes. Coronary deaths were classified on the basis of histologic features. The number of acute plaque ruptures, healed plaque ruptures, vulnerable plaques, and acute plaque erosions were compared between groups. Postmortem values of serum total cholesterol, HDL cholesterol, and thiocyanate were measured, and menopausal status was confirmed by calculating body mass index. Results Women older than 50 years of age were much more likely to have a ruptured plaque than were younger, premenopausal women. Plaque rupture was significantly associated with elevated total cholesterol level. In the 51 women who died of coronary disease, the mean number of vulnerable plaques increased significantly as women advanced into the postmenopausal years. Conclusions Our data suggest that estrogen has an anti-inflammatory effect on atherosclerotic plaques, resulting in plaque stabilization. Plaque erosion, the major substrate for thrombosis in premenopausal women, does not appear to be inhibited by estrogen. Because plaque progression may result both from repeated rupture and repeated erosion, a better understanding of the effect of estrogen on atherosclerosis may yield insights into the nature of coronary artery disease. (Am Heart J 2001;141:S58-62.)

Localization of Apoptotic Macrophages at the Site of Plaque Rupture in Sudden Coronary Death

Although apoptosis is a well-recognized phenomenon in chronic atherosclerotic disease, its role in sudden coronary death, in particular, acute plaque rupture is unknown. Culprit lesions from 40 cases of sudden coronary death were evaluated. Cases were divided into two mechanisms of death: ruptured plaques with acute thrombosis (n = 25) and stable plaques with and without healed myocardial infarction (n = 15). Apoptotic cells were identified by staining of fragmented DNA and confirmed in select cases by gold conjugate labeling combined with ultrastructural analysis. Additional studies were performed to examine the expression and activation of two inducers of apoptosis, caspases-1 and -3. Ruptured plaques showed extensive macrophage infiltration of the fibrous cap, in particular at rupture sites contrary to stable lesions, which contained fewer inflammatory cells. Among the culprit lesions, the overall incidence of apoptosis in fibrous caps was significantly greater in ruptured plaques (P < 0.001) and was predominantly localized to the CD68-positive macrophages. Furthermore, apoptosis at plaque rupture sites was more frequent than in areas of intact fibrous cap (P = 0. 028). Plaque rupture sites demonstrated a strong immunoreactivity to caspase-1 within the apoptotic macrophages; staining for caspase-3 was weak. Immunoblot analysis of ruptured plaques demonstrated caspase-1 up-regulation and the presence of its active p20 subunit whereas stable lesions showed only the precursor; nonatherosclerotic control segments were negative for both precursor and active enzyme. These findings demonstrate extensive apoptosis of macrophages limited to the site of plaque rupture. The proteolytic cleavage of caspase-1 in ruptured plaques suggests activation of this apoptotic precursor. Whether macrophage apoptosis is essential to acute plaque rupture or is a response to the rupture itself remains to be determined.

Coronary calcification: insights from sudden coronary death victims.

We studied 108 cases of sudden coronary death at autopsy. Any calcification was present in 55% of men and women under 40 years; all hearts showed some calcification by age 50 in men, and by age 60 in women. The only risk factor independently associated with increased calcification was diabetes mellitus, in women only. The degree of calcification was greatest for acute and healed plaque ruptures, and the least for plaque erosion. Calcification in coronary atherosclerosis appears to be delayed in women, is greatest in women diabetics, and is associated with one type of plaque instability, namely plaque rupture.

Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women.

Traditional risk factors have been linked to atherosclerotic heart disease in women. However, the effect of risk factors and menopausal status on the mechanism of sudden coronary death is unknown. We examined 51 cases of sudden coronary death and 15 hearts from women who died of trauma. Coronary deaths were divided into four mechanisms of death: ruptured plaque with acute thrombus (n = 8), eroded plaque with acute thrombus (n = 18), stable plaque with healed infarct (n = 18), and stable plaque without infarction (n = 7). Vulnerable plaques prone to rupture were defined as those with a thin, fibrous cap infiltrated by macrophages and were quantitated in coronary deaths and control subjects. Total cholesterol (TC), HDL cholesterol, glycosylated hemoglobin, cigarette smoking, and hypertension were determined in each case. Compared with control subjects, women with plaque ruptures had elevated TC (270 +/- 55 versus 194 +/- 44 mg/dL, P = 0.002), and those with erosions were more likely to be smokers (78% versus 33%, P = 0.01). Women with stable plaque and healed infarct had elevated glycosylated hemoglobin (10.2 +/- 5.0% versus 6.4 +/- 0.4% in control subjects, P = 0.001) and were more likely to be hypertensive (50% versus 15% in control subjects, P = 0.03). By multivariate analysis, cigarette smoking was associated with plaque erosion (P = 0.03, odds ratio [OR] 21), glycoslyated hemoglobin with stable plaque and healed infarct (P = 0.03, OR 41), TC with plaque rupture (P = 0.02, OR 7), and hypertension with stable plaque with healed infarct (P = 0.02, OR 15). Seven of 8 plaque ruptures occurred in women > 50 years of age versus 3 of 18 erosions (P = 0.001). In cases of coronary death, vulnerable plaques were associated with elevated cholesterol (P = 0.002) and age > 50 years (P = 0.002), independent of other risk factors. In women, traditional risk factors have distinct effects on the mechanisms of sudden coronary death, which vary by menopausal status. Effective risk factor modification may therefore differ between younger and older women and may be targeting different mechanisms of plaque instability.

Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction.

Ischemic heart disease includes a wide spectrum of conditions, ranging from silent ischemia and exertion-induced angina, through unstable angina, to acute MI. Unstable angina occupies the center of this spectrum, causing disability and risk greater than that of chronic stable angina but less than that of acute MI1 (Fig 1⇓). Although non–Q-wave MI for many years was considered prognostically similar to unstable angina, recent longitudinal studies indicate that it is similar to Q-wave infarction2 3 (Fig 2⇓). Figure 1. Cumulative 6-month mortality from ischemic heart disease. Diagnosis on admission to hospital (n=21 761; 1985 to 1992). From Duke Cardiovascular Database. Reproduced with permission from Reference 1. Figure 2. Top, Cumulative 1-year combined death or MI among patients with Q-wave and non–Q-wave MI treated with fibrinolysis. Reproduced with permission from Reference 2. Bottom, Risk of subsequent cardiac events in stable convalescing patients after first non–Q-wave and Q-wave MI. Reproduced with permission from Reference 3. The concept of unstable angina has emerged from observations of frequent symptoms preceding acute MI, followed by prospective documentation that unstable symptoms frequently culminated in acute MI. The syndrome was rapidly accepted as a well-defined clinical entity as specific clinical manifestations, pathophysiological mechanisms, laboratory findings, and treatment became better characterized. Unstable angina is currently one of the leading causes of hospital admission for CAD, and non–Q-wave MI accounts for >30% of admissions for acute MI.1 4 Yet, the diagnosis of unstable angina remains clinical, based on symptom recognition. The physician caring for patients with unstable angina is in a privileged position of recognizing rapidly evolving CAD and being able to intervene to prevent irreversible left ventricular damage and progression of CAD. Unstable angina is classically described as a heterogeneous disease, referring to a wide spectrum of clinical manifestations from stable angina to MI, of disease …

Stressful events as a trigger of sudden death: a study of 43 medico-legal autopsy cases

The reports relating emotional stress to sudden death are largely anecdotal. In addition to experimental and electrophysiological studies, an opportunity for a better understanding of possible stress-related sudden death (SSD) may be provided by medico-legal autopsies. The goal of our autopsy study was to analyze cardiovascular pathologic findings in cases of SSD and if possible identify mechanisms by which the stressful event (SE) could be the cause. Forty three cases were studied (29 males and 14 females). In all cases, the SE and the death were witnessed. The age range was 22 to 90 years in males (mean, 52) and 30 to 92 years in females (mean, 64). Death occurred in all cases without premonitory symptoms. In 20 cases, death occurred during the SE and in the other 23 cases occurred within 2 h of the event. SE included fear, 15 cases; altercation, 21 cases; sexual activity, 3 cases; police questioning or arrest, 4 cases. According to police reports, in 40 cases (90%), the victims had no previous clinical history of cardiovascular disease. At autopsy, the heart weight in males ranged from 255 to 1000 g with a mean of 517 g and in females the range was 250–700 g with a mean of 417 g. In only 3 cases, gross and microscopic examination of the heart was normal. In 2 of the remaining 40 cases the subjects died of subarachnoid hemorrhage. In 38 cases, a cardiac cause of death was found as follows: coronary heart disease, 27 cases; cardiomyopathy, 6 cases; aortic valvular stenosis, 2 cases and right ventricular dysplasia, 3 cases. A coronary artery thrombosis was found in 8 cases of sudden coronary death. Post myocardial infarction fibrosis was present in 25 cases (92%) of sudden coronary death. In conclusion, it appears from our autopsy study that SSD occurs primarily in those individuals with severe heart disease, especially coronary heart disease.

Sudden coronary death. Frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction.

The reported frequency of active coronary lesions (plaque rupture and coronary thrombosis) in sudden death due to coronary artery atherosclerosis (sudden coronary death) has varied from < 20% to > 80% of cases in previous series. In hearts lacking an active coronary lesion, sudden death has usually been attributed to a healed myocardial infarction. The purpose of the present study was to determine the frequency of active and inactive coronary lesions and myocardial infarction in individuals with sudden coronary death. The hearts of persons who died as a result of sudden coronary death underwent perfusion-fixation and postmortem angiography. An active coronary lesion was defined as a disrupted plaque, luminal fibrin/platelet thrombus, or both. We defined an inactive lesion as having a cross-sectional luminal stenosis of > or = 75% with neither plaque disruption nor luminal thrombus. Ninety hearts were examined (from 72 men and 18 women; mean age at the time of death, 51 +/- 10 years). Acute myocardial infarction was present in 19 (21% [acute myocardial infarction only in 9, both acute and healed myocardial infarction in 10]), healed myocardial infarction only in 37 (41%), and no myocardial infarction in 34 (38%). Active coronary lesions were identified in 51 (57%): acute thrombi plus disrupted plaques in 27, acute thrombi only in 21, and disrupted plaques only in 3. In hearts with acute myocardial infarction, active coronary lesions were significantly more prevalent than in hearts with only healed myocardial infarction or hearts lacking an acute or a healed myocardial infarction (89%, 46%, and 50%, respectively; P < .005). Hearts without acute or healed myocardial infarction and without active lesions were similar to hearts with active lesions with respect to heart weight and severity of epicardial coronary disease. Acute changes in coronary plaque morphology (thrombus, plaque disruption, or both) were found in 57% of cases of sudden coronary death. In hearts with myocardial scars and no acute infarction, active coronary lesions were identified in 46% of cases. Neither myocardial infarction (acute or healed) nor an active coronary lesion was present in 19% of hearts.

A pathological study of sudden coronary death in China: Report of 89 autopsy cases

This paper reports the results of a forensic pathological study of 89 autopsy cases of Sudden Coronary Death (SCD). Of 89 cases, 63 (52 male, 11 female) were narrowed by 76–100% in cross-selectional area (XSA) of the coronary artery (CA) and 26 (22 male, 4 female), by 51–75%. Atherosclerotic plaques in the CA were serious and extensive, especially in the left anterior descending and often involved several branches of CA at the same time. Recent thrombosis was found in 18 cases, haemorrhage in plaques in 17 cases. Only 2 cases had visible acute myocardial infarction. Inflammatory cell infiltration was found in coronary plaques in 36 cases. Myocardial fibrosis or small scar formation was detected in 51 cases. It is suggested that although the incidence of coronary heart disease (CHD) is low in China, SCD is the commonest mode of Sudden Unexpected Death. The majority of SCD (52%) were middle aged males (30–49 years old). Most of the cases died suddenly during sleep without any clear precipitating factors. The characteristics of occurrence and pathological changes in the CA and myocardium and the pathological diagnosis of SCD are also analysed and discussed.

Diagnosis of sudden coronary death in the autopsy room: guidelines for forensic pathologists.

The pathological techniques employed in examining cases of sudden coronary death can vary widely. Visual assessment of coronary narrowing can lead to over-estimation of the true stenosis and may result in overdiagnosis of sudden coronary death. On the other hand, inappropriate examination of the whole epicardial coronary tree while searching for acute coronary lesions may lead to underdiagnosis. The approach recommended in this paper should minimize the possibility of such errors in the diagnosis of sudden coronary death.

Reproductive history of women dying of sudden cardiac death: a case-control study.

Reproductive history events may be risk factors for sudden coronary death (SCD) among women. A retrospective case-control study of SCD among women aged 25-64 was conducted in Allegheny County, Pennsylvania. The present analysis focused on a description and analysis involving the childbearing and reproductive history of 67 ever-married female SCD cases and 73 ever-married neighbourhood controls with a mean age of 54.6 and 53.4 years respectively. Information included: age and number of years married, number of children, age at first birth, cardiovascular risk factors, obstetric and gynaecological history. Age and the risk factors, history of hypertension or diabetes, cigarette intake, death of significant other and psychiatric disease, were controlled for in the analysis. More cases than controls experienced their first birth before age 20 (14 of the SCD and 7 controls). However, after adjustment for cigarette smoking status, a strong predictor of sudden cardiac death, the effect of early childbearing did not remain significant for this population. In women less than or equal to 50 years of age, childlessness was not a risk factor for SCD (1 of 16 cases and 2 of 26 controls were childless). However in women greater than 50 years of age, childlessness was a significant predictor of SCD (OR = 6.7 (1.3-32] 12 of 51 cases were childless compared to 2 of 46 controls. After adjustment for aged and other coronary heart disease (CHD) risk factors, the relationship of nulliparity with sudden cardiac death remained in this age group. There was no difference in hysterectomy or miscarriage history or in the total years married between cases and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

New theory on the pathogenesis of acute myocardial infarction.

Autopsy studies of hearts from 140 patients who had suffered acute myocardial infarction (AMI) and 26 cases of sudden coronary death revealed two distinct types of myocardial cell death: "kinetic cell death" (KD) and "static cell death" (SD). In KD, the predominant type of cell death in AMI-myofibrils disintegrated through alternating overcontraction and overextension. KD was found not only in patients having died after some time had elapsed from the onset of AMI, but also in cases of sudden coronary death. Muscle fibers in SD, which by contrast began to appear at least seven hours after the onset of AMI, characteristically preserved cross striations, while their nuclei were pyknotic or had already disappeared. Such fibers were observed only in territories peripheral to occlusive coronary thrombus, a secondary rather than a primary event that takes place during the course of AMI. As a result of the above observations, we were able to produce a new experimental model of AMI using mongrel dogs. As a preparatory procedure we first injected them intravenously with 2% calcium chloride at a constant rate for 90 or 120 minutes, and then with a sudden injection of caffeine, calcium chloride and catecholamine in order to induce KD. In contrast, ligation of the intraventricular coronary artery near its origin caused SD of myocardial fibers in the dependent territories. Overall results led us to conclude that AMI is initiated by instantaneous overcontraction of myocardial fibers, resulting in their KD, a phenomenon that could be called "myocardial self-destruction."