Report on Cardiac Gross Pathologic Measurements of Sudden Cardiac Death in Adults / 法医学杂志

OBJECTIVES@#To analyze the gross pathological data of sudden cardiac death (SCD) with different causes, to provide data support for the identification of sudden cardiac death with unknown causes.@*METHODS@#A total of 167 adult SCD cases in the archive of the Forensic Expertise Institute of Nanjing Medical University from 2010 to 2020 were collected. The gross pathological data of SCD cases were summarized and the characteristics of different causes of death were statistically analyzed.@*RESULTS@#The ratio of male to female SCD cases was 3.4∶1. Coronary heart disease was the leading cause of SCD, and mainly distributed in people over 40 years old. SCD caused by myocarditis was mainly distributed in young people and the mean age of death was (34.00±9.55) years. By analyzing the differences in cardiac pathological parameters of SCD with different causes, it was found that the aortic valve circumference was significantly dilated in the SCD caused by aortic aneurysm or dissection (P<0.05). The heart weight of SCD caused by aortic aneurysm or dissection and combined factors was greater, and both pulmonary and tricuspid valvular rings were dilated in the SCD caused by combined factors in adult males (P<0.05).@*CONCLUSIONS@#Various gross pathological measures of SCD with different causes are different, which has reference value in the cause of death identification of SCD.

Research Progress and Forensic Application of Postmortem Genetic Testing in Hereditary Cardiac Diseases / 法医学杂志

Hereditary cardiac disease accounts for a large proportion of sudden cardiac death (SCD) in young adults. Hereditary cardiac disease can be divided into hereditary structural heart disease and channelopathies. Hereditary structural heart disease mainly includes hereditary cardiomyopathy, which results in arhythmia, heart failure and SCD. The autopsy and histopathological examinations of SCD caused by channelopathies lack characteristic morphological manifestations. Therefore, how to determine the cause of death in the process of examination has become one of the urgent problems to be solved in forensic identification. Based on the review of recent domestic and foreign research results on channelopathies and hereditary cardiomyopathy, this paper systematically reviews the pathogenesis and molecular genetics of channelopathies and hereditary cardiomyopathy, and discusses the application of postmortem genetic testing in forensic identification, to provide reference for forensic pathology research and identification of SCD.

Research Progress on Molecular Markers Related to Unexplained Sudden Cardiac Death and Its Forensic Application / 法医学杂志

Routine pathological examination of unexplained sudden cardiac death (USCD) lacks significant morphological characteristics. In the field of forensic medicine, molecular biology methods have been used to find the cause of death by detecting genes and research related to the mechanism of sudden cardiac death has been carried out. From the molecular pathology point of view, the application of multiple levels of biomarkers to resolve the causes of USCD has already shown potential and provides an important path for forensic identification of USCD. This article reviews the latest research progress on USCD-related genes, RNA, proteins and USCD, and summarizes forensic application.

Forensic Pathology Analysis of 363 Sudden Death Cases in Yunnan Province / 法医学杂志

OBJECTIVES@#To study the epidemiological and pathological features of sudden death （SD） in Yunnan Province and to provide scientific evidence for prevention and forensic identification of sudden death.@*METHODS@#Totally 363 SD cases were collected from the autopsies between 2009 and 2017 in the Forensic Centre of Kunming Medical University. The related factors such as etiology, age, inducing factor, time interval between the onset of disease and death, morbidity season and pathological change were retrospectively analysed.@*RESULTS@#The incidence of SD in males was significantly higher than that of females. The peak age was ≥35-55 years. The mortality rate was relatively high within 6 h after the onset of disease. The season order with descending number of deaths was spring, summer, winter and autumn. The top ten causes of SD were coronary heart disease, sudden unexplained death （SUD）, cerebral hemorrhage, acute hemorrhagic necrotic pancreatitis, aortic dissection rupture, cardiomyopathy, pneumonia, pulmonary thromboembolism, amniotic fluid embolism and allergy. Exercise, infusion, surgery, medication and minor injury were the most common predisposing factors of sudden coronary death. Consciousness disorder or coma, chest pain or chest tightness, and abdominal pain were the most common premortem symptoms of sudden coronary death.@*CONCLUSIONS@#The SD is more common in middle-aged males, which is the key population for the prevention of SD. For the forensic identification and prevention of SD, the attention on SUD should be paid.

Research Progress of the Correlation between Caveolin and Unexpected Sudden Cardiac Death / 法医学杂志

Due to the negative autopsy and without cardiac structural abnormalities, unexpected sudden cardiac death （USCD） is always a tough issue for forensic pathological expertise. USCD may be associated with parts of fatal arrhythmic diseases. These arrhythmic diseases may be caused by disorders of cardiac ion channels or channel-related proteins. Caveolin can combine with multiple myocardial ion channel proteins through its scaffolding regions and plays an important role in maintaining the depolarization and repolarization of cardiac action potential. When the structure and function of caveolin are affected by gene mutations or abnormal protein expression, the functions of the regulated ion channels are correspondingly impaired, which leads to the occurrence of multiple channelopathies, arrhythmia or even sudden cardiac death. It is important to study the effects of caveolin on the functions of ion channels for exploring the mechanisms of malignant arrhythmia and sudden cardiac death.

Morte Súbita na Cardiomiopatia Hipertrófica / Sudden Death in Hypertrophic Cardiomyopathy

A cardiomiopatia hipertrófica é uma doença genética do músculo cardíaco, autossômica dominante, caracterizada por hipertrofia ventricular na ausência de qualquer outra condição clínica que leve à sobrecarga do coração. Estima-se prevalência de 1:500, sendo importante causa de morte súbita, especialmente em jovens, com incidência anual em torno de 1%. Entre os marcadores de risco para a ocorrência de arritmias ventriculares malignas e morte súbita neste cenário, enfatizam-se, além de um evento fatal já ocorrido e abortado, história familiar de morte súbita; espessura de parede maior ou igual a 30mm; síncope inexplicada; presença de taquicardia ventricular não sustentada ao Holter; resposta pressórica anormal no teste ergométrico; e presença de realce tardio na ressonância magnética do coração. A presença ou ausência destes marcadores pode definir a necessidade ou não do implante de cardiodesfibrilador implantável como forma de prevenir a morte súbita nestes pacientes. Entretanto, ainda existe muita controvérsia sobre a forma pela qual estes pacientes devam ser estratificados. Sabe-se que estes marcadores não têm o mesmo peso em predizer quem tem mais chance de sofrer um evento fatal. Este fato torna-se particularmente importante quando se constata que o procedimento de implante de cardiodesfibrilador implantável não é isento de complicações, além do impacto econômico, em termos do custo para o sistema de saúde. A proposta deste artigo é a realização de uma revisão sobre os principais aspectos envolvidos na morte súbita destes pacientes, desde a fisiopatologia, a avaliação de risco, a prevenção e as perspectivas futuras.

Pathological Features of Myocardial Contraction Band Necrosis in Sudden Cardiac Death / 法医学杂志

OBJECTIVE@#To investigate the pathological features and significance of myocardial contraction band necrosis in sudden cardiac death.@*METHODS@#Using HE and PTAH staining, the distribution sites and pathological features of myocardial contraction band necrosis were observed. The data were analyzed according to the extent of necrosis.@*RESULTS@#The locations, pathological features and the extent of necrosis were similar in different sudden death cases. The locations were related with sites of myocardial damage. The papillary muscles of left ventricular were most occurred, followed by the anterior wall of left ventricular. In the sudden death cases caused by stress cardiomyopathy, the extent of myocardial contraction band necrosis was lighter than the others. Most cases were predominantly level 1, the others were level 2.@*CONCLUSION@#Used as the diagnosis basis of acute myocardial ischemia, the myocardial contraction band necrosis has important significance to determination of death.

Early Repolarization and Myocardial Scar Predict Poorest Prognosis in Patients with Coronary Artery Disease

PURPOSE: Recent studies show positive association of early repolarization (ER) with the risk of life-threatening arrhythmias in patients with coronary artery disease (CAD). This study was to investigate the relationships of ER with myocardial scarring and prognosis in patients with CAD. MATERIALS AND METHODS: Of 570 consecutive CAD patients, patients with and without ER were assigned to ER group (n=139) and no ER group (n=431), respectively. Myocardial scar was evaluated using cardiac single-photon emission computed tomography. RESULTS: ER group had previous history of myocardial infarction (33% vs. 15%, p<0.001) and lower left ventricular ejection fraction (57+/-13% vs. 62+/-13%, p<0.001) more frequently than no-ER group. While 74 (53%) patients in ER group had myocardial scar, only 121 (28%) patients had in no-ER group (p<0.001). During follow up, 9 (7%) and 4 (0.9%) patients had cardiac events in ER and no-ER group, respectively (p=0.001). All patients with cardiac events had ER in inferior leads and horizontal/descending ST-segment. Patients with both ER in inferior leads and horizontal/descending ST variant and scar had an increased adjusted hazard ratio of cardiac events (hazard ratio 16.0; 95% confidence interval: 4.1 to 55.8; p<0.001). CONCLUSION: ER in inferior leads with a horizontal/descending ST variant was associated with increased risk of cardiac events. These findings suggest that ER in patients with CAD may be related to myocardial scar rather than pure ion channel problem.

Expression of monocyte chemotactic protein-1 and its receptor in sudden coronary death / 法医学杂志

OBJECTIVE@#To investigate the expression of monocyte chemotactic protein-1 (MCP-1) and its receptor CC chemokine receptor-2 (CCR-2) in coronary atherosclerosis plaques between sidden coronary death (SCD) and non-SCD. Methods The expression levels of MCP-1 and CCR-2 in SCD group, coronary atherosclerosis group (non-SCD), control group (normal coronary artery) were detected by immunohistochemistry.@*RESULTS@#Positive rates of MCP-1 among the three groups were 78%, 47%, and 0%, respectively, with significant expressing differences between each two groups (P<0.05). Positive rates of CCR-2 among three groups were 72%, 47%, and 0%, respectively, with significant expressing differences between the SCD group and coronary atherosclerosis group as well as between the SCD group and control group (P<0.05), but with no significant expressing difference between coronary atherosclerosis group and control group (P>0.05).@*CONCLUSION@#Overexpression of MCP-1 and CCR-2 in coronary atherosclerotic plaques is closely correlated with SCD.

Origem anômala da artéria coronária esquerda do seio de Valsalva direito / Anomalous origin of the left coronary artery from the right sinus of Valsalva

Trazemos neste artigo a descrição de uma peça anatômica especificamente preparada para demonstrar uma rara anomalia da origem da artéria coronária esquerda do seio de Valsalva direito, com incidência de 0,15% em pacientes submetidos a cinecoronariografia. Trata-se de um subgrupo de anomalias das artérias coronárias que tem o maior potencial para repercussões clínicas, em especial a morte súbita em jovens. Discutimos, à luz dos conhecimentos atuais, os mecanismos fisiopatológicos, o diagnóstico e as opções de tratamento das variações anatômicas da origem anômala da artéria coronária do seio contralateral.

This article reports an anatomic specimen specifically prepared to demonstrate a rare anomaly of the origin of the left coronary artery from the right sinus of Valsalva, with an incidence of 0.15% in patients undergoing coronary angiography. This is a subgroup of coronary artery anomalies with the greatest potential for clinical repercussions, especially sudden death in young patients. Based on current knowledge, pathophysiologic mechanisms, diagnosis and treatment options of anatomical variations of the anomalous origin of a coronary artery from the contralateral sinus are discussed.

Myocardial expression of Spry1 and MAPK proteins of viral myocarditis / 法医学杂志

OBJECTIVE@#To discuss the myocardial expression of Spry1 and MAPK proteins of viral myocarditis (VMC), to reveal its mechanism of sudden death, and to provide guides for forensic identification of sudden cardiac death.@*METHODS@#Thirty Balb/c male mice were randomly divided into VMC group and control group, inoculated intraperitoneally with Coxsackievirus B3 and Eagel's solution, respectively. After the mice were sacrificed, the cardiac tissues of the mice were taken to proceed regular pathological examination. The changes of Spry1 protein, Spry1 mRNA and MAPK protein were detected by immunohistochemistry, Western blotting and real-time PCR.@*RESULTS@#Under light microscope, the pathologic changes included myocardial interstitial edema, inflammatory cells infiltration, myocardial necrosis, and focal and patchy necrosis of myocardial fiber in VMC group. The expression of Spry1 protein in VMC group was lower than that in control group (P < 0.05). There was slightly decreased expression of Spry1 of the mRNA level in VMC group (P > 0.05). But the MAPK protein expression in VMC group was higher than that in control group (P < 0.05).@*CONCLUSION@#The pathway of MAPK/ERK involving Spry1 protein accelerates the expression of collagen, which may contribute to arrhythmia, heart failure and even sudden cardiac death.

The role and significance of microRNA in human cardiovascular disease and forensic science / 法医学杂志

microRNA (miRNA or miR) is a small single stranded non-coding RNA (21-25nt) that regulates gene expression in almost creatures. Currently, plenty of researches on how miRNA affects human cardiovascular disease have been reported. This review highlights recent findings about the role of miRNA in heart tissue and circulation correlated with human cardiovascular disease and explores the application of miRNA in sudden cardiac death in forensic science.

Application of molecular autopsy in sudden death caused by inherited arrhythmia / 法医学杂志

Sudden cardiac death (SCD) refers to sudden stop of breath and heartbeat and death within one hour caused by underlying cardiac diseases. Clinical manifestation of inherited arrhythmia is lethal arrhythmia without gross cardiac lesions, which can lead to SCD. The autopsy and pathological examination are difficult to identify the cause of death. Fatal mechanism of inherited arrhythmia is the change in the genes encoding for cardiac ion channel protein, which causes the dysfunctions of cardiac electrical activity. It is very important to detect genetic mutation by the technique of molecular biology in negative autopsy. This review presents the latest research on the relation between SCD and inherited arrhythmia, and the application of molecular autopsy used in identifying SCD due to inherited arrhythmia and its candidate gene.

Expression of fas protein of myocardium in dilated cardiomyopathy / 法医学杂志

OBJECTIVE@#To investigate Fas protein expression of the myocardium in dilated cardiomyopathy (DCM) and its relationship with occurrence of sudden death caused by DCM.@*METHODS@#Nine autopsy cases of sudden death caused by DCM along with the heart samples were chosen from the archives in the Department of Forensic Medicine, Tongji Medical College, HUST from 1997 to 2007. Other 11 cases which died of violence and other diseases were selected as the control group. Expressions of myocardial Fas protein in the samples were quantitatively detected by immunohistochemistry and computerized imaging analysis.@*RESULTS@#Myocardial Fas protein expression increased significantly in the DCM group. Positive color showed brown-yellow granulated or striped distribution in the longitudinal section of myocardial within the cell membrane and cytoplasm, and showed circular brown granules in the cross section of the cell membrane, while these changes were not observed in the control group though there was focal weak staining noted. Statistical significance was observed between the experimental and control groups (P = 0.002), but no statistical significance was found for the average optical density value between these two groups (P = 0.675).@*CONCLUSION@#The expression of Fas protein increased obviously in the DCM group. Such alteration in expression quantity and distribution of myocardial Fas protein may be related to arrhythmia and heart failure in the patients with DCM.

Application of serum total IgE, tryptase and chymase in the identification of death caused by drug anaphylactic shock / 法医学杂志

OBJECTIVE@#To explore the application value of serum total IgE, tryptase and chymase in the identification of death caused by drug anaphylactic shock.@*METHODS@#The general information from 235 cases of non-drug anaphylactic shock and 32 cases of drug anaphylactic shock were analyzed. The serum IgE level had been detected in the cases. Ten cases caused by coronary disease and 10 cases caused by sudden manhood death syndrome were selected from non-drug anaphylactic shock cases for the control group. Expressions of tryptase and chymase in the lung and heart were detected using immunohistochemistry method. The number and IOD of positive mast cells were counted.@*RESULTS@#In the drug anaphylactic shock group, the IgE value of 18 samples (56.25%) was significantly higher than the normal upper limit of 120 IU/mL. In the non-drug anaphylactic shock group, the IgE value of 67 samples (28.51%) was higher than 120 IU/mL. The expressions of tryptase and chymase were significantly increased in lung and myocardial tissue in drug anaphylactic shock group (P < 0.05).@*CONCLUSION@#Tryptase and chymase are more superior than that of the serum total IgE in the diagnosis of death caused by drug anaphylactic shock, and are more suitable in forensic practice.

Pathological characteristics of sudden death caused by coronary thrombosis / 法医学杂志

OBJECTIVE@#To explore medico-legal characteristics of sudden death caused by coronary heart disease combined with coronary thrombosis.@*METHODS@#Ninety-six cases of sudden death caused by coronary heart disease were collected and divided into two groups: thrombus positive and thrombus negative groups. The time onset, induction and pathological features of coronary artery disease were analyzed.@*RESULTS@#Two groups showed man-dominant population. There were no statistical significant differences in season, circadian rhythm and induction factor. The thrombus positive group (age < 40) showed a higher disease incidence. Heart weight and degree of coronary stenosis were lower in thrombus positive group. However, there was no statistical difference in the number of atherosclerotic coronary arteries (> or = 2), the length of coronary lesions and myocardial infarct. But thrombosis positive group showed lower tendency.@*CONCLUSION@#Two groups are man-dominant population and similar induction factor, lesion position, mechanism of death. But thrombus positive group appeared more in a younger population and the degree of coronary stenosis is milder than thrombus negative group. Forensic pathologists should pay more attention to these characteristics in death investigation.

Estudio clínico patológico sobre muerte súbita cardíaca: Pathological clinical study / Cardiac sudden death: Pathological clinical study

El objetivo de este estudio fue describir la evolución de la muerte súbita cardíaca (MSC) en las comunidades de Arroyo Naranjo durante el período 2000-2004. Se realizó un estudio descriptivo con 5 098 fallecidos de muerte natural en ese municipio. El presente trabajo incluyó 474 pacientes procedentes de las áreas de salud del municipio Arroyo Naranjo, La Habana, que presentaron una muerte súbita cardíaca (MSC) en el periodo 2000-2004. La pérdida de la conciencia y la disnea fueron los síntomas más frecuentes (72,4 por ciento y 36,9 por ciento). Los principales factores de riesgo fueron la enfermedad isquémica coronaria crónica (59,3 por ciento) y la hipertrofia ventricular izquierda (52,7 por ciento). El infarto agudo del miocardio (58,4 por ciento) y los trastornos del ritmo cardíaco (20,7 por ciento) fueron los diagnósticos definitivos que más se asociaron al fallecimiento inesperado, confirmándose por la necropsia

The objective of present paper was to describe the sudden death course (SDC) in communities from Arroyo Naranjo municipality during 2000-2004. A descriptive study was conducted in 5098 deceased persons from natural death in above municipality. Present paper included 474 patients from that health area who had a cardiac sudden death (CSD). The more frequent symptoms were consciousness loss and dyspnea (72.4 percent and 36.9 percent). The leading risk factors were the chronic ischemic disease (59.3 percent) and the left ventricular hypertrophy (52.7 percent). The acute myocardial infarction (58.4 percent) and the cardiac rhythm disorders (20.7 percent were the definitive diagnoses more associated with the repens death, verified by necropsy

Frequência de rupturas agudas de placas e fibroateromas de capa fina em locais de estenose máxima / Frecuencia de rupturas agudas de placas y fibroateromas de capa fina en locales de estenosis máxima / Frequency of acute plaque ruptures and thin cap atheromas at sites of maximal stenosis

FUNDAMENTO: Poucos estudos de autópsia relacionam locais de fibroateromas de capa fina (FCF) a locais de ruptura aguda de placas em artérias responsáveis, e locais de estreitamento máximo em artérias não responsáveis. OBJETIVO: O objetivo do presente estudo foi quantificar e localizar a frequência de FCF em relação aos locais de estenose máxima em placas ateroscleróticas. MÉTODOS: Estudamos 88 corações em vítimas de morte súbita devido a um tromo coronariano sobreposta a ruptura aguda da placa. Fibroateromas de capa fina foram definidos como capa fibrosa < 65 mícrons sobrepostos a um núcleo necrótico. O percentual de estreitamento luminal foi determinado nos locais de ruptura de placa e fibroateromas de capa fina. RESULTADOS: O estudo foi composto por 81 homens e 7 mulheres com idade média de 50 anos ± 9 DP. A ruptura da placa se deu no local de estreitamento luminal máximo em 47 por cento das artérias responsáveis. Observou-se a presença de FCFs em 67 corações (83 por cento). Desse número, 49 (73 por cento) demonstravam FCFs na artéria responsável; 17 (25 por cento) apenas na artéria responsável, 32 (48 por cento) na artéria responsável e na artéria não responsável, e 18 (27 por cento) apenas em uma artéria não responsável. Em artérias não responsáveis, os FCFs representaram o local máximo da estenose em 44 por cento das artérias. O local da ruptura aguda foi o local do estreitamento luminal máximo nos vasos envolvidos em 47 por cento de corações de pacientes próximos do óbito devido à ruptura da placa. CONCLUSÃO: Esses dados podem sugerir que o estreitamento luminal não é um marcador confiável para FCF.

BACKGROUND: There have been few autopsy studies relating sites of thin cap atheroma (TCFA) to sites of acute plaque rupture in culprit arteries, and sites of maximal narrowing in non-culprit arteries. OBJECTIVE: We aimed to quantify and locate the frequency of TCFA related to the sites of maximal stenosis in atherosclerotic plaques. METHODS: We studied 88 hearts in victims of sudden death dying with coronary thrombus overlying acute plaque rupture. Thin cap atheromas were defined as fibrous cap < 65 microns overlying a necrotic core. Percent luminal narrowing was determined at the sites of plaque rupture and thin cap atheromas. RESULTS: There were 81 men and 7 women, mean age 50 years ± 9 SD. The plaque rupture was the site of maximal luminal narrowing in 47 percent of culprit arteries. TCFAs were present in 67 hearts (83 percent). Of these, 49 (73 percent) demonstrated TCFAs in the culprit artery; 17 (25 percent) in the culprit artery only, 32 (48 percent) in the culprit artery and in a non-culprit artery, and 18 (27 percent) only in a non-culprit artery. In non-culprit arteries, TCFAs represented the maximal site of stenosis in 44 percent of arteries. The acute rupture site is the site of maximal luminal narrowing in the involved vessel in 47 percent of hearts from patients dying with acute plaque rupture. CONCLUSION: These data may suggest that luminal narrowing is not a reliable marker for TCFA.

FUNDAMENTO: Pocos estudios de autopsia relacionan locales de fibroateromas de capa fina (FCF) a locales de ruptura aguda de placas en arterias responsables, y locales de estrechamiento máximo en arterias no responsables. OBJETIVO: El objetivo del presente estudio fue cuantificar y localizar la frecuencia de FCF con relación a los locales de estenosis máxima en placas ateroscleróticas. MÉTODOS: Estudiamos 88 corazones en víctimas de muerte súbita debido a un trombo coronario sobrepuesto a ruptura aguda de la placa. Fibroateromas de capa fina fueron definidos como capa fibrosa < 65 micrones sobrepuestos a un núcleo necrótico. El porcentaje de estrechamiento luminal fue determinado en los locales de ruptura de placa y fibroateromas de capa fina. RESULTADOS: El estudio estuvo compuesto por 81 hombres y 7 mujeres con edad promedio de 50 años ± 9 SD. La ruptura de la placa se dio en el local de estrechamiento luminal máximo en el 47 por ciento de las arterias responsables. Se observó la presencia de FCFs en 67 corazones (83 por ciento). De ese número, 49 (73 por ciento) mostraban FCFs en la arteria responsable; 17 (25 por ciento) sólo en la arteria responsable, 32 (48 por ciento) en la arteria responsable y en la arteria no responsable, y 18 (27 por ciento) sólo en una arteria no responsable. En arterias no responsables, los FCFs representaron el local máximo de la estenosis en el 44 por ciento de las arterias. El local de la ruptura aguda fue el local del estrechamiento luminal máximo en los vasos involucrados en el 47 por ciento de corazones de pacientes próximos al óbito debido a la ruptura de la placa. CONCLUSIÓN: Estos datos pueden sugerir que el estrechamiento luminal no es un marcador confiable para FCF.