Impact of Myocardial Infarction and Abnormalities of Cardiac Conduction System on Sudden Cardiac DeathCSCD

Sudden cardiac death (SCD), most commonly seen in coronary heart disease, is a kind of sudden death caused by series of cardiac parameters, which usually combines with myocardial infarction. However, some SCDs (including early myocardial infarction) happen suddenly and cause death in a very short time. In these circumstances, typical morphological changes are lack in macroscopic or microscopic fields, which make such SCDs become the emphasis and difficulty in the present research. SCD caused by myocardial infarction and abnormalities of cardiac conduction system (CCS) is related to atherosclerosis of coronary artery closely. This paper reviews cardiac dysfunction caused by myocardial infarction and diseases of CCS from morphology and molecular biology, and explores potential relationship between them. This paper aims to provide clues to the mechanism of myocardial infarction related sudden death and possible assistance for forensic diagnosis of SCD. © 2017 by the Editorial Department of Journal of Forensic Medicine.     

心肌缺血猝死心肌中高迁移率族蛋白B-1的表达研究

目的探讨高迁移率族蛋白B-1(High Mobility Group Box protein 1,HMGB1)在心肌缺血猝死后诊断中的法医学价值。方法收集不同案例心肌蜡块分为疑似早期心肌缺血猝死组(早期梗死组)20例、心肌梗死猝死组(心肌梗死组)15例、冠心病非心源性猝死组(对照组1)10例和正常心肌组(对照组2)10例,应用免疫组织化学二步法染色,观察心肌胞核和胞浆中HMGB1表达,用ImagePro Plus 6.0软件计算HMGB1表达的平均光密度,用SPSS 13.0对表达进行数据统计分析。结果 HMGB1在四组心肌细胞胞核中表达均呈阳性;早期梗死组和心肌梗死组胞浆均呈阳性表达,对照组1和对照组2胞浆呈阴性。各组平均光密度分别为0.3031±0.0557、0.3195±0.0523、0.0252±0.0030、0.0207±0.0029,早期梗死组和心肌梗死组的阳性反应与两个对照组相比存在显著差异(P﹤0.01)。结论 HMGB1可作为早期心肌缺血猝死的一个辅助诊断指标。     

急性心肌缺血猝死心肌中血红素加氧酶-1的表达

目的观察血红素加氧酶-1（HO-1）在急性心肌缺血猝死心肌细胞胞浆中的表达情况。方法应用免疫组织化学技术（SP法）,对27例可疑早期心肌缺血猝死（早期梗死组）、10例心肌梗死猝死（心肌梗死组）、11例冠心病非心性猝死（对照组1）以及10例正常心肌（对照组2）中HO-1的表达进行观察分析。结果早期梗死组与心肌梗死组在心肌细胞胞浆中HO-1均呈强阳性表达,对照组1和对照组2心肌细胞胞浆中HO-1弱阳性表达或无表达。早期梗死组和心肌梗死组与对照组1和对照组2之间心肌细胞内HO-1表达的差异有显著性意义（P（0.01）;镜下各组心肌细胞胞浆内HO-1表达的阳性面积率及平均光密度差别明显。结论 HO-1可以作为急性心肌缺血所致心性猝死的一个诊断指标。     

Sudden Cardiac Death in a Young Man with Migraine-associated Arrhythmia

A 31-year-old man with migraine-induced syncope and bradycardia with subsequent pacemaker implantation died unexpectedly. Clinically unsuspected cardiac anomalies were found at autopsy including myocardial bridging of the left anterior descending artery and shelf-like coronary artery ostia. Nortriptyline was identified by toxicologic analysis. A review of the autopsy findings, the historical information, and the effects of the possible arrhythmogenic circumstances is undertaken and the potential contributions to the death are discussed. Cardiac arrhythmias have been documented during migraines. Coronary artery bridging has been known to lead to ischemia and infarction, ventricular tachycardia, and sudden death; however, these are very rare sequelae. Congenital coronary artery anomalies have been linked to sudden cardiac death, but only rarely cause death in people younger than 31 years. Migraines and the autopsy findings described have been associated with cardiac arrhythmia and sudden death. Altogether, they led to the unexpected death of this young man.     

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.     

A Case of Sudden Infant Death Due to Incomplete Kawasaki Disease

Although Kawasaki disease (KD) is a self‐limiting disease, it may cause sudden cardiac death. Diagnosis of KD is principally based on clinical signs; however, some infant cases do not meet the criteria. Such cases are identified as incomplete KD. The sudden death risk in incomplete KD cases is similar to conventional KD. In our 5‐month‐old case, he had been admitted to a hospital for a fever and suppuration at the site of Bacille de Calmette et Guerin (BCG) vaccination. However, after discharge from the hospital, his C‐reactive protein (CRP) levels declined, he got indisposed and died suddenly. A medico‐legal autopsy revealed myocarditis, coronaritis, platelet‐aggregated emboli in coronary arteries, and myocardial degeneration, suggesting that the fatal myocardial infarction was due to thrombus emboli in the coronary arteries. Forensic pathologists therefore should pay attention to the cardiac pathology originated from incomplete KD as a potential cause in cases of sudden infant death.     

Spontaneous dissection of the distal obtuse marginal coronary artery: a rare cause of sudden death

Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction and sudden death. It typically, but not always, occurs in healthy postpartum women without traditional risk factors for atherosclerosis. Moreover, the site of dissection usually involves the proximal, major coronary arteries: left main coronary artery and/or the left anterior descending artery, and in men, more often the right coronary artery. We report a case of sudden death caused by dissection of the obtuse marginal branch of the left circumflex artery, in a 49-year-old man, a very rare site of fatal coronary dissection.     

Travel, time zones, and sudden cardiac death. Emporiatric pathology

In an 11-year retrospective study of coroner's autopsies on the Hawaiian island of Kauai, it was found that an unusual and apparently unique subset of travelers died suddenly. Death was caused by coronary arteriosclerosis, was characterized by acute coronary changes, and occurred in a group younger than the usual age for sudden cardiac death. Visitors with two-vessel disease had an incidence of sudden death nearly four times that of Kauaians (p less than 0.02), with a ninefold increase of coronary thrombosis (p less than 0.001), a sixfold prevalence of old myocardial infarcts (p less than 0.001), and three times the prevalence of cardiomegaly (p less than 0.001). The circadian pattern of these deaths was different from that previously described in acute myocardial infarction or sudden death, with the number of incidents rising steadily through the day in contrast to the morning peak described in previously published series. The syndrome was expressed in decedents with two-vessel coronary disease either with acute coronary artery lesions--thrombosis, hemorrhage in a plaque, or ruptured coronary artery--or no lesions, presumably spasm. Underlying chronic processes included enlarged heart or old myocardial infarct, which both occurred with a significantly greater incidence in travelers than in local residents, and in a totally different pattern from that occurring in subjects with three-vessel disease. It is postulated that the syndrome is caused by stress related to travel and time zone changes.     

Primary study of vascular endothelial growth factor immunohistochemical staining in the diagnosis of early acute myocardial ischemia

The expression of vascular endothelial growth factor (VEGF) in the model of rat early acute myocardial ischemia was studied by Strept-Avidin-Biotin-Peroxidase Complex (SABC) immunohistochemical staining. After ligating the anterior descending branch of the left coronary artery, an initial rapid (30min) positive expression of VEGF in myocardial ischemic areas was observed, the intensity of positive expression of VEGF increased with the continuation of myocardial ischemia. After 5h infarction, the strongly positive myocytes of SABC-VEGF staining were predominantly limited to perimyocardial infarction areas. No positive expression of VEGF was found in the control group. These findings suggested that SABC-VEGF method could give a sensitive, specific, simple and objective morphologic evidence to the diagnosis of sudden cardiac death caused by acute early myocardial ischemia.     

Aortic Dissection and Sudden Unexpected Deaths: A Retrospective Study of 31 Forensic Autopsy Cases

Acute aortic dissection (AAD) is the most common cause of sudden unexpected death related to aortic diseases. A retrospective study of 31 sudden unexpected deaths caused by AAD was conducted at Xi'an Jiaotong University Forensic Center from 2001 to 2012. We summarized the forensic characteristics of AAD and assessed the clinically diagnostic accuracy of AAD. The characteristics of sudden unexpected death due to AAD were male predominant (male: female = 6.7:1), relatively young with the mean age of 44, and predominance of type A dissection (77.4%). Cardiac tamponade was the most frequent cause of sudden death (87.1%). Of the 31 cases, 26 (83.9%) patients were not recognized clinically and were misdiagnosed with acute myocardial infarction, coronary artery disease, cholecystitis, acute gastroenteritis, renal/urinary lithiasis, or acute pancreatitis. In summary, AAD can be difficult to recognize, diagnosis is therefore sometimes delayed or missed. The medicolegal death investigation can help physicians have a better understanding of AAD.     

Spontaneous Coronary Artery Dissection: Case Report and Literature Review

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction and sudden cardiac death. It occurs most commonly in otherwise healthy women during pregnancy or the postpartum period. The true incidence of SCAD is underestimated, as most cases are diagnosed at autopsy. The pathophysiology of SCAD is still not fully understood, and its management can be challenging. This report describes a 35‐year‐old pregnant female who presented with an acute antero‐lateral ST elevation secondary to spontaneous dissection of the left anterior descending artery and the circumflex artery. The diagnosis was established by coronary artery angiography. However, the patient died following cardiac tamponade. The examination of this case represented a starting point for the reviewing of the diagnosis, clinical course, and management of SCAD, and for the placing of this in context with the existing literature. This study highlights the importance of prompt diagnosis and subsequent lifesaving treatment.     

A study of various morphologic variables and troponin I in pericardial fluid as possible discriminators of sudden cardiac death

Pathologists frequently examine victims of sudden cardiac death. In some cases, a firm diagnosis of cardiac-related death can be made based on conclusive gross and histologic findings. In many other cases, we find evidence supportive of, but not diagnostic of, cardiac death (e.g., atherosclerotic coronary artery disease, cardiomegaly, myocardial scarring). A final cohort consists of cases of sudden death with minimal to mild cardiac disease, no other significant pathology, and negative toxicologic studies. This prospective study compared 38 cardiac-related deaths with 52 control cases with respect to concentrations of pericardial cardiac troponin I (cTnI), heart weight, evidence of old and/or recent myocardial injury, and presence of significant coronary artery disease. The influence of documented chest trauma and/or perimortem cardiopulmonary resuscitation (CPR) on levels of cTnI was also analyzed. Even though median cTnI levels were significantly higher in cardiac deaths than in controls (p = .003), cTnI was not found to be a significant predictor of cardiac deaths, as determined by discriminant analysis (p = .52). Heart weight >500 g, evidence of old and recent myocardial injury, and significant coronary artery disease were seen statistically more often in cardiac deaths than in controls (p < or = .005 in each case), and median age was significantly higher in cardiac deaths than in controls (p = .001). Based on a stepwise logistic regression model, significant coronary artery disease, old and recent myocardial injury, and heart weight >500 g were found to contribute significantly to the prediction of cardiac death. Finally, neither chest injury nor CPR significantly affected concentrations of cTnI in pericardial fluid. These data confirm that the presence of acute and remote myocardial injury, significant coronary artery disease, and cardiomegaly (heart weight >500 g) strongly supports the diagnosis of a cardiac-related death. In contrast to a recently published report, we do not find that elevated concentrations of cTnI in pericardial fluid are strong indicators of cardiac-related deaths using our methodology.     

Cardiac pathology in 470 consecutive forensic autopsies

Cardiovascular disease continues to be the single most common generic cause of sudden and unexpected deaths. Atherosclerotic coronary heart disease and acute myocardial infarction are the most prevalent forms of fatal cardiac disease observed at autopsy. Other cardiac lesions are frequently listed as causes of death, but the prevalence of such lesions as incidental findings in the general population is unknown. In this study, 470 consecutive forensic autopsies were evaluated for minor and major anomalies. The most frequently observed major congenital finding was floppy mitral valve (5%). Tunneled coronary arteries, considered minor congenital findings, were seen in 29%. Atherosclerotic coronary heart disease was the most common major acquired finding, observed in 16% of cases. Of the 470 hearts, only 8% were considered normal.     

早期心肌梗死死后诊断的法医病理学研究进展

心源性猝死在成人猝死的死因中占首位,心肌梗死是冠心病猝死的主要机制之一,由于早期心肌梗死发生突然,且可在短时间内死亡,肉眼和镜下都缺乏典型的形态学改变,一直都是法医实践中研究的热点,本文回顾多年来心肌梗死的研究成果在法医学中的应用及局限,展望新的临床指标在法医工作中的可行性,期望提高死后心肌梗死诊断的准确率。     

Left Ventricular Aneurysm: Sudden Unexpected Deaths in a 29‐Year‐Old Man

Left ventricular aneurysm (LVA) is an abnormal dilated heart structure, either congenital or acquired. LVA is a rare cardiac condition with no symptoms in most cases, thus occasionally diagnosed during investigations of other diseases. Its association with certain cardiac complications and sudden cardiac deaths has been reported. However, its role as a cause of sudden unexpected death is rare. The author reported a sudden cardiac death in a 29‐year‐old man with LVA. Without a significant coronary artery disease and known etiologies of LVA, such an abnormal heart structure in the present case was considered congenital LVA. As no other possible mechanisms of death could be identified other than LVA with its associated pathologic lesions, mural thrombi, and dilated cardiomegaly, his death was attributable to fatal cardiac arrhythmia (most commonly ventricular tachycardia) secondary to LVA.     

Detection of apoptosis in ischemic heart. Usefulness in the diagnosis of early myocardial injury

Myocardial samples of hearts with histologic findings of acute myocardial infarction (group A), sudden coronary deaths without histologic changes (group B), and chronic ischemic heart disease (group C) were analyzed to investigate the appearance of apoptosis in acute and chronic ischemic cardiac disorders. This analysis involved the morphologic detection of DNA strand breaks in myocyte nuclei by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and the biochemical determination of DNA laddering in the myocardium using archival formalin-fixed, paraffin-embedded tissue sections of human myocardium. The authors demonstrated that apoptosis of myocardial cells could occur after ischemic myocardial cell injury. In all documented cases of acute myocardial infarction (group A), the infarcted area included extensive presence of both apoptosis and necrosis. In the tissue bordering on and away from the obviously infarcted areas, positive nuclei were intermingled with nonstained normal myocytes. The number of positive nuclei decreased with the distance from the infarction foci. In group B, myocardial samples showed focal or diffuse nuclear positivity of varying degrees for apoptosis, confirming the presence of myocardial ischemic cell death, whereas the histologic diagnosis remained inconclusive. This finding suggests that apoptosis could be used as a marker for acute ischemic injury. In group C, stained nuclei were dispersed with intermingled normal cardiomyocytes.     

冠心病猝死的病理学研究——附128例尸检分析

本文报道128例冠心病猝死的法医病理学研究结果。其中冠脉病变4级63例,3级26例,2级29例。3级以上病变者斑块分布多较广泛。各支病变中以左前降支最常见。并发新鲜血栓形成者18例,斑块内出血17例,急性心肌梗死仅2例。36例冠脉斑块有炎性细胞浸润。56例见心肌间质纤维化或小灶疤痕形成。指出虽然我国冠心病发病率较低,但仍是猝死最常见的原因,尤以中壮年男性多见;多数病例无明显诱因而于睡眠中猝死。对冠心病猝死发生的特点、冠脉和心肌病变及病理诊断等进行了分析讨论。     

早期心肌缺血猝死心肌NF-κB p65的表达研究

目的探讨核因子NF-κBp65（NF-κB p65）在心肌早期缺血猝死后诊断中的法医学价值。方法将收集的案例心肌蜡块分为3组：正常对照组（3例）、早期心肌缺血组（14例）、心肌梗死组（8例）,采用免疫组织化学技术（SP法）,观察猝死心肌内NF-κBp65的表达情况,并对其结果进行半定量分析。结果早期心肌缺血组和心肌梗死组的心肌细胞胞浆内及细胞核内均出现NF-κBp65的表达,且早期心肌缺血组与心肌梗死组表达强度无差异。结论NF-κBp65可以作为早期心肌缺血猝死的一个辅助诊断指标。     

Serum concentrations of cardiac troponin T in sudden death

Ischemic heart disease is the most common cause of sudden death of natural causes in most western countries. By autopsy, there may be no gross or histologic evidence of acute myocardial damage unless the patient survived for several hours following the event. Cardiac troponin in serum has become the recommended biochemical marker for myocardial injury in the clinical setting. We performed a prospective study on 102 autopsied subjects at the Central Hospital of Rogaland, Stavanger, Norway. Femoral blood was sampled for subsequent analysis of cardiac troponin T (cTnT). In the subjects with morphologic evidence of recent myocardial injury (n = 34), the mean serum cTnT level was 1.95 microg/L compared with 0.16 microg/L in the subjects with a noncardiac cause of death (n = 35) and 0.61 microg/L in the group with probable sudden cardiac death without morphologic signs of acute myocardial injury (n = 33). The observed differences in mean serum cTnT levels between the groups were statistically significant (P < 0.0001). These data suggest that elevated postmortem serum concentration of cTnT reflects ongoing myocardial damage and may support a diagnosis of cardiac-related death in cases associated with sparse or inconclusive morphologic findings postmortem.     

缺血修饰白蛋白在急性缺血性心脏病中的法医学应用

目的探讨心包液中缺血修饰白蛋白(ischemia modified albumin,IMA)水平在心脏性猝死诊断中的应用价值及法医学意义。方法应用白蛋白-钴离子结合法检测急性缺血性心脏病组(36例)、急性心肌梗死组(6例)、心肌病组(4例)、对照组(15例)死者的心包液中IMA水平,比较各组之间IMA水平的差异。通过ROC曲线获得最佳IMA水平的截断值以及区分急性缺血性心脏病和对照组的敏感度和特异度。结果急性缺血性心脏病组心包液中IMA水平高于对照组(P0.05);而与急性心肌梗死组、心肌病组心包液中IMA水平比较,差异均无统计学意义(P0.05)。应用ROC曲线分析得出识别急性心肌缺血的IMA的截断值为40.65 U/m L,其诊断急性心肌缺血的敏感度为60.0%,特异度为80.5%。结论心包液中IMA有望作为诊断急性心肌缺血的参考指标,为心脏性猝死的法医学诊断提供客观依据。