Second opinion system for sudden cardiac death cases in forensic practice

International Journal of Legal Medicine - Sudden cardiac death (SCD) represents a considerable percentage of cardiovascular deaths worldwide. The most frequent pathological substrate of SCD is...     

Retrospective analysis of 769 cases of sudden cardiac death from 2006 to 2015: a forensic experience in China

Sudden cardiac death (SCD) is a major health challenge. The records of 769 autopsy cases of SCD examined at Tongji Medicolegal Expertise Center from January 2006 to December 2015 were retrospectively reviewed. The mean age of the cases was 46 years, excluding 27 victims in whom the exact age could not be confirmed. The highest incidence of SCD occurred among the 40- to 60-year-old group (45.0%). Male preponderance was observed in SCD cases (male: female ratio: 5.0:1), and this preponderance was even higher (8.0:1) in the 10- to 20-year-old and 60- to 70-year-old groups. Death predominantly occurred in hospitals (37.4%) and outdoors (32.5%). The incidence of SCD did not differ significantly between the seasons. Coronary atherosclerotic disease (CAD) was the main cause of SCD (67.9%), followed by unexplained SCD (6.1%), myocarditis (5.7%), cardiomyopathy (4.7%), rupture of aortic dissection (3.9%), and cardiac conduction system disease (3.9%). In terms of the CAD cases, the mean age was 52.0 years and coronary artery stenosis exceeding 75% accounted for 73.6% of cases. The left anterior descending branch was involved with atherosclerosis in 92.0% of cases. In conclusion, detailed autopsy and forensic pathology examination is key to diagnosing SCD. Making an early diagnosis and performing early intervention of CAD may reduce the mortality of SCD. Additionally, the use of molecular genetic tests plus forensic pathology diagnosis will help further determine the underlying cause of death in individuals with SCD.     

Genetic analysis of sudden cardiac death victims: a survey of current forensic autopsy practices

Autopsy-negative sudden cardiac deaths (SCD) seen in forensic practice are most often thought to be the result of sudden arrhythmic death syndrome. Postmortem genetic analysis is recommended in such cases, but is currently performed in only a few academic centers. In order to determine actual current practice, an on-line questionnaire was sent by e-mail to members of various forensic medical associations. The questions addressed routine procedures employed in cases of sudden cardiac death (autopsy ordering, macroscopic and microscopic cardiac examination, conduction tissue examination, immunohistochemistry and electron microscopy, biochemical markers, sampling and storage of material for genetic analyses, toxicological analyses, and molecular autopsy). Some questions concerned the legal and ethical aspects of genetic analyses in postmortem examinations, as well as any existing multidisciplinary collaborations in SCD cases. There were 97 respondents, mostly from European countries. Genetic testing in cases of sudden cardiac death is rarely practiced in routine forensic investigation. Approximately 60% of respondents reported not having the means to perform genetic postmortem testing and 40% do not collect adequate material to perform these investigations at a later date, despite working at university hospitals. The survey demonstrated that many of the problems involved in the adequate investigation of SCD cases are often financial in origin, due to the fact that activities in forensic medicine are often paid by and dependent on the judicial authorities. Problems also exist concerning the contact with family members and/or the family doctor, as well as the often-nonexistent collaboration with others clinicians with special expertise beneficial in the investigation of SCD cases, such as cardiologists and geneticists. This study highlights the importance in establishing guidelines for molecular autopsies in forensic medicine.     

缺血心肌动物模型PET和SPECT显像及组织学对比研究

目的评估^201TI SPECT及^18F-脱氧葡萄糖（FDG）PET显像对模型猪心肌活力的鉴别。方法健康家猪12头，其中10头于冠状动脉左旋支起始处放置Ameriod环，饲养28d形成慢性心肌缺血动物模型（另2头作正常对照），行^201TI SPECT心肌灌注显像和^18F—FDG PET心肌代谢显像并与HE染色病理学改变进行比较。结果81个心肌节段中，^18F—FDG心肌显像示心肌有活力的节段为73个（90．1％），明显高于^201TI心肌显像所示的62个（76．5％），差异有显著性（P〈0．05）。HE染色结果示有心肌活力的节段为74个（91．3％），与^18F—FDG心肌显像所示结果差异无显著性（P〉0．05）。结论^18F—FDGPET心肌显像检测心肌活力的准确性明显高于^201TI SPECT心肌显像。     

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.     

Contrast agents and cardiac MR imaging of myocardial ischemia: from bench to bedside

This review paper presents, in the first part, the different classes of contrast media that are already used or are in development for cardiac magnetic resonance imaging. A classification of the different types of contrast media is proposed based on the distribution of the compounds in the body, their type of relaxivity and their potential affinity to particular molecules. In the second part, the different uses of the extracellular type of T1-enhancing contrast agent for myocardial imaging is covered from the detection of stable coronary artery disease to the detection and characterization of chronic infarction. A particular emphasis is placed on the clinical use of gadolinium-chelates, which are the universally used type of MRI contrast agent in the clinical routine. Both approaches, first-pass magnetic resonance imaging (FP-MRI) as well as delayed-enhanced magnetic resonance imaging (DE-MRI), are covered in the different situations of acute and chronic myocardial infarction.     

A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

An updated approach to sudden cardiac death,the AECVP perspective

International Journal of Legal Medicine -     

Postmortem genetic testing should be recommended in sudden cardiac death cases due to thoracic aortic dissection

Background

Acute thoracic aortic dissections and ruptures, the main life-threatening complications of the corresponding aneurysms, are an important cause of sudden cardiac death. Despite the usefulness of the molecular diagnosis of these conditions in the clinical setting, the corresponding forensic field remains largely unexplored. The main goal of this study was to explore and validate a new massive parallel sequencing candidate gene​ assay as a diagnostic tool for acute thoracic aortic dissection autopsy cases.

Materials and methods

Massive parallel sequencing of 22 thoracic aortic disease candidate genes performed in 17 cases of thoracic aortic dissection using AmpliSeq and Ion Proton technologies. Genetic variants were filtered by location, type, and frequency at the Exome Aggregation Consortium and an internal database and further classified based on the American College of Medical Genetics and Genomics (ACMG) recommendations published in 2015. All prioritized results were confirmed by traditional sequencing.

Results

From the total of 10 potentially pathogenic genetic variants identified in 7 out of the 17 initial samples, 2 of them were further classified as pathogenic, 2 as likely pathogenic, 1 as possibly benign, and the remaining 5 as variants of uncertain significance, reaching a molecular autopsy yield of 23%, approximately.

Conclusions

This massive parallel sequencing candidate gene approach proved useful for the molecular autopsy of aortic dissection sudden cardiac death cases and should therefore be progressively incorporated into the forensic field, being especially beneficial for the anticipated diagnosis and risk stratification of any other family member at risk of developing the same condition.

     

惠州市188例院前猝死特点分析

目的:探讨惠州市院前猝死特点,提高惠州市院前抢救的成功率.方法:回顾惠州市2000-01～2003-12期间院前死亡病例,对资料完整且符合猝死诊断标准的188例院前猝死病例的临床特征及其流行病学特点进行分析.结果:188例猝死患者中,男性115例(61.17%),女性73(38.83%),男女比例1.58:1,随年龄增大,死亡数增多.以冬、春季多发,夜间(63%)多发.结论:对高危人群应加强预防指导及医学监护、普及急救医学知识,加强第一目击者抢救能力,完善急救医疗服务系统,争取抢救时间,提高复苏技术是最大限度抢救病人,减少死亡的有效方法.     

A sudden death due to cardiac conduction system injury from a blunt chest impact

We report a case of sudden death due to cardiac conduction system injury from a blunt chest impact. A 20 year old male, kicked in the precordial region, lost consciousness, and was confirmed dead on arrival at a hospital emergency care unit. According to his friends, they played a golf competition accompanied with a physical punishment. The victim, losing the game, allowed the winner to give him several kicks in the chest. Although well prepared against each kick, he fell down instantaneously after the final impact, and death was confirmed at a hospital. There was no apparent sign of injury on the body surface. At autopsy, there was no evident subcutaneous or intramuscular hemorrhages, rib or sternum fracture. Subendocardial hemorrhage in the region of the atrioventricular node and a contusion extending from the posterior wall of the left ventricle to the upper ventricular septum were observed. Histological examination revealed injury of atrioventricular node and His' bundle. Although the cardiac injury including contusion of the myocardium itself was not so extensive, it was considered that arrhythmia was induced by the cardiac conduction system failure, which was considered to be the cause of death.     

Prior myocardial infarction is the major risk factor associated with sudden cardiac death during downhill skiing

More than 90% of all sudden cardiac deaths (SCDs) during downhill skiing, the most popular winter sport world-wide, are attributed to men over the age of 34. However, no data exist on additional risk factors and triggers for SCD related to downhill skiing. Therefore risk factor profiles of 68 males who died from SCD during downhill skiing were compared to those of 204 matched controls. Skiers who suffered SCD had much more frequently prior myocardial infarction (MI) (41% vs. 1.5%; p<0.001), hypertension (50% vs. 17%; p<0.001), known coronary heart disease (CHD) without prior MI (9% vs. 3%; p=0.05) and were less engaged in strenuous exercise (4% vs. 15%; p<0.05) when compared to controls. Multivariate analyses even enhanced the importance of these risk factors. Downhill skiing is considered to be a serious trigger for SCD especially in skiers with prior MI but also for those with hypertension, known CHD without prior MI, or insufficient adaptation to strenuous exercise. Skiing-related increased sympathetic activity might well disturb the autonomic balance with subsequent arrhythmias and/or may increase cardiac work and platelet aggregability with possible plaque rupture and coronary thrombosis. Therefore adaptation to high intensity exercise and therapeutic interventions or abstinence from skiing in certain cases should be considered for downhill skiers at high risk.     

Two forensic autopsy cases of death from unexpected lesions of the pituitary gland

Herein, we report the findings of 2 forensic autopsy cases, in which unexpected pituitary lesions were the underlying cause of death.Case 1: A 56-year-old woman was found dead at her home during a cold winter spell. Macroscopic autopsy findings included a difference in the color of blood that filled her left and right cardiac chambers (deep red and dark red, respectively), collapse of both lungs, atrophy of the thyroid gland, and a large tumor arising from the sella turcica. Microscopic examination revealed a pituitary adenoma along with extensive bleeding. The cause of death was considered to be hypothermia, resulting from dysregulation of thermogenesis due to the pituitary adenoma.Case 2: An 86-year-old man with a history of pollakiuria was found dead in a bathtub, with his face and chest submerged in bathwater and his legs positioned outside the bathtub. The macroscopic findings of the autopsy included hyper-inflated lungs, fluid collection in the thoracic cavity, and aspiration of gastric contents in the bronchi. The atherosclerotic changes of the man’s coronary and cerebral arteries were considered mild for his age. Microscopic examination showed a marked infiltration of lymphocytes and plasma cells in the posterior pituitary gland, as well as in the liver, pancreas, and submandibular gland. Considering the results of the autopsy and the findings from the investigation conducted at the death scene, we concluded that the man probably lost consciousness following a neurally mediated syncope, which was induced by diabetes insipidus (lymphocytic hypophysitis). After losing consciousness, the man likely fell in the filled bathtub and then drowned.These 2 cases highlight the need for a thorough post-mortem investigation, including a microscopic examination of the pituitary gland. In addition, forensic pathologists should carefully study the pituitary gland in cases where the cause of death is thought to be related to dysfunction of thermoregulation or osmoregulation.     

Postmortem cardiac troponin T levels in the blood and pericardial fluid. Part 2: analysis for application in the diagnosis of sudden cardiac death with regard to pathology

Although previous forensic pathological studies have suggested the possible application of cardiac troponins in the diagnosis of myocardial infarction, there appears to be insufficient data with regard to its cardiac pathology. The present study analyzed the heart blood, peripheral blood and pericardial fluid levels of cardiac troponin T (cTnT) in sudden cardiac deaths (n = 96) within 48h postmortem in relation to pathological findings of acute myocardial infarction (AMI, n = 34), recurrent myocardial infarction (RMI, n = 23), ischemic heart disease without any pathological evidence of infarction (IHD, n = 24) and other heart diseases (OHD, n = 15). Control groups (n = 75, survival time <24 h) within 48 h postmortem consisted of asphyxiation (n = 35), drowning (n = 27) and cerebrovascular diseases (n = 13). There was a marked correlation in the cTnT levels between right and left heart blood samples. The pericardial level was usually higher than either heart blood level, and the external iliac venous blood level was the lowest. Although postmortem time-dependent increases in heart and pericardial blood cTnT levels were observed in most groups, they were most evident for AMI and asphyxiation. In the early postmortem period (<12 h) there was no significant difference between AMI or RMI and the other groups except for drowning. After 12 h postmortem, significantly elevated heart blood and pericardial cTnT levels were observed for AMI and RMI showing multiple interstitial hemorrhages and necrosis compared to those with localized eosinophilic changes or patchy interstitial hemorrhages, IHD and OHD. These differences were the smallest for peripheral blood. For sudden cardiac death cases, the difference in cTnT level at each site among the causes of death was independent of gender, age, heart or lung weight and pathologies of affected coronary artery and severity of coronary stenosis. These observations suggest that the elevation in postmortem blood and pericardial cTnT levels in sudden cardiac death may depend on the severity of ischemic myocardial damage including the size and intensity of myocardial lesions involving multiple interstitial hemorrhages and necrosis, and also the postmortem period for heart and pericardial levels.     

A forensic autopsy case: Sudden unexpected death due to cardiac inflammatory myofibroblastic tumor

We report an autopsy case of a 25-year-old man with no medical history who died suddenly in an Internet cafe. He was found in cardiorespiratory arrest and did not respond to cardiopulmonary resuscitation. Traumatic lesions were not observed on his body. An autopsy was performed to investigate the cause of death. Upon examination, we discovered a heart tumor that infiltrated from the outside wall to the outflow tract of the left ventricle. Left ventricular outflow tract obstruction due to a cardiac tumor was considered the mechanism of death. Histological examination identified an inflammatory myofibroblastic tumor (IMT). The final diagnosis was death secondary to circulatory failure due to a cardiac IMT. Additionally, a cardiac tumor was diagnosed using post-mortem computed tomography. Only few cases of sudden unexpected death due to cardiac IMT have been reported; we report this case along with a review of the literature.     

Bulbo-spinal pathology in neurocardiac sudden death of adults: a pragmatic approach to a neglected problem

This paper gives an overview on the neurocardiopathy of reflexogenic sudden death in adults, focusing on the bulbo-spinal cardiovascular-respiratory centers and which is reminiscent of the recent findings in sudden infant death syndrome. The preeminent life-threatening derangements of the oxygen-conserving cardio-inhibitory reflex (dive-reflex and its subsets) were reconsidered in histopathology, together with bulbo-spinal sympathovagal abnormalities and possible underlying arrhythmogenic QT interval prolongation. A simplified methodology for the microscopical examination of the brain stem and upper thoracic spinal cord is suggested. The aim is to facilitate the pathologist’s approach to a lamentably neglected, yet fundamental topic in the far-reaching domain of sudden cardiac death with no evidence of cardiovascular respiratory disease. Received: 27 October 1997 / Received in revised form: 9 February 1998     

38例院前猝死回顾性调查

目的分析老年患者发生院前猝死的危险因素。方法回顾性分析北京某社区1993-2004年38例老年院前猝死病例,调查猝死患者生前已诊断疾病情况,猝死前状态及诱因、发病季节及时间。结果高血压、冠心病、糖尿病是老年猝死患者生前罹患比率最高的前三位基础疾病,分别占78．94％、55．26％和44．73％。4月份猝死事件发生最多;73．68％发生在早6时～晚6时;发生在患者家中占81．57％。结论老年患者心血管疾病可能是导致猝死的主要原因,有心肌梗死、心律失常、心功能不全的患者是发生猝死的高危人群;事件发生突然,往往无明显先兆。