Giant cell myocarditis with cardiac tamponade: a rare combination

Giant cell myocarditis (GCM) is a rare but fatal disease of idiopathic origin. It results in focal necrosis of myocardium. This is a case report of middle aged Malaysian Indian female who died due to cardiac tamponade due to rupture myocardium and tear in the root of aorta. On naked eye examination, it simply resembled as recent as well as old fibrotic areas of myocardial infarction. She was clinically diagnosed as a case of obstructive cardiomyopathy with atrioventricular block, and was on pace maker. There was subendocardial fibrosis and left ventricular transmural infarction in the left ventricle. On histopathology, this was diagnosed as GCM, there were widespread areas of inflammatory cellular infiltration within the myocardium with multinucleated giant cells and granulomas interspersed with lymphocytes. Microscopic field showed up to 10 multinucleated giant cells. In this case, there were focal areas at multiple locations and caused uneven thickness in the left ventricle wall. Idiopathic GCM is very rare and causation of hemopericardium is the unique feature of this case. In this case the direct link of GCM with aortitis and rupture of left ventricle wall resulting in hemopericardium is shown. This case is documented through macroscopic as well as microscopic photographs in H&E, Ziel-Nelson, and GMS staining.     

Mutational analysis of TTN,TCAP and TPM1 in cardiomyopathy

Resent molecular genetic study revealed that defects in sarcomeric genes causes cardiomyopathies. Comprehensive screening of 3 sarcomeric genes: TTN (titin), TCAP (telethonin) and TPM1 (alpha-tropomyosin) were performed in 35 consented autopsy cases diagnosed as cardiomyopathy. One nonsynonymous mutation p.Val9710Ile detected in TTN, which located on binding region to cardiac ankyrin repeat protein was found in one DCM case. It was suggested that the mutation might alter interaction of the Z-disc components and caused cardiomyopathy. A single nucleotide polymorphism p.Ala151= found in TCAP had significant differences in gene frequency between DCM and control cases. It is necessary to analyze the other sarcomeric genes and clarify the relationship with aetiology.     

Right ventricular damage due to pulmonary embolism: examination of the number of infiltrating macrophages

To investigate the pathological changes in the heart induced by pulmonary embolism, 20 autopsy cases of pulmonary embolism and 10 control cases of acute death from traumatic injury were examined. Adding to the routine hematoxylin-eosin (HE) staining, immunostaining with CD68 pan-macrophage marker was performed on the specimens obtained from both right and left ventricular walls. The number of macrophages was counted semi-quantitatively in 100 random high-power fields (HPF). Although typical pathological findings of myocardial infarction was not observed in any of the cases, 16 of the 20 pulmonary embolism cases showed an increase in the number of macrophages, mainly in the right ventricular wall. Four cases showed massive macrophage infiltration in the entire right ventricular wall. It is speculated that ischemia due to pulmonary embolism may be connected to its pathogenesis.     

致心律失常性右心室心肌病

致心律失常性右心室心肌病是以右心室心肌被脂肪或纤维脂肪组织取代为特征的一种原因尚不明确的心肌病。目前已公认是年轻人猝死的重要原因之一。ARVC最显著的病理学特征是弥散性或节段性的右心室游离壁心肌的缺失及纤维脂肪组织的替代,从组织形态学可将ARVC分为两型:(1)单纯脂肪型;(2)纤维脂肪型。与纤维脂肪组织取代右心室心肌有关的发病机制:(1)细胞凋亡或程序性细胞死亡理论;(2)炎症理论;(3)心肌发育不良理论;(4)肌细胞转分化理论。     

Myocardial Cx43 expression in the cases of sudden death due to dilated cardiomyopathy

PURPOSE: Probing into myocardial connexin (Cx) 43 expression in the cases of sudden death due to dilated cardiomyopathy (DCM) and relationship between Cx43 expression and sudden death. METHOD: Myocardial Cx43 was detected with immunohistochemical staining in the cases of 11 sudden death caused by DCM and 14 cases of control group who died of violent reasons and other diseases, which were autopsied in our department from 1997 to 2003. RESULT: Of 11 cases of DCM, there were 10 men and 1 woman with ranging in age from 7 to 49 years old (x (37.8) years old for 9 adult cases). Of 14 cases in the control group, there were 10 men and 4 women with ranging in age from 11 to 53 years old (x (29.9) years old for 11 adult cases). Myocardial Cx43 expression was obviously decreased in DCM group. Positive dyeing spots were different in size, distribution, color and disparity, some of them were distributed in the form of particle. Obvious change had not been observed in the cases of control group or with only slight changes in coloring degree and expressive area. The quantitative data showed that there was significant difference between two groups (p=0.0075) about Cx43 expressive area, but there was no difference between the left and right ventricles (p>0.05) in each group itself. And there was not difference between the two groups about average optical density of expression. CONCLUSION: Myocardial Cx43 expression is obviously reduced in the patients with DCM who die suddenly. The alteration of quantity and distribution of myocardial Cx43 expression is probably related to sudden death of the patients with DCM.     

Sudden cardiac death and right ventricular dysplasia.

Right ventricular cardiomyopathy dysplasia, now a well-established clinical and morphologic entity, was first reported in the medical literature in 1982. The cases of sudden death of two young men are here reported, with macroscopic and histologic findings. The anatomical explanation of such death was a fibrotic, lipomatous, or fibrolipomatous replacement and infiltration of the myocardium of the right ventricle. It is suggested that death due to right ventricular cardiomyopathy seems to be the result of electrical instability of right ventricular myocardium. There were no congenital malformations such as septal defect or valvular deformity. The subjects' heart weights were normal. Signs of myocardial degeneration and necrosis with or without inflammatory infiltrates were not identified.     

A case of sudden infant death due to a primary cardiac sarcoma

The case reported herein concerns the unexpected death of a 3-month-old female newborn who suddenly collapsed in her mother's arms and was dead on arrival at the hospital. The clinical histories of the baby and her parents were negative for symptoms or signs of illness, even those of cardiovascular origin. Furthermore, no clinical appearance of a pathologic status was noted by pediatricians after the birth until the last emergency recovery. The autopsy excluded external and internal signs of violence but revealed a large primary cardiac tumor arising from the free wall of the left ventricle, which had totally invaded the heart causing mitral valve deformation. Histological examination showed a low-grade sarcoma that completely infiltrated the myocardial tissue. The pathogenesis of this sudden infant death was postulated as being owing to a fatal ventricular fibrillation combined with a tumor-related restrictive cardiomyopathy obstructing left ventricular filling.     

病毒性心肌炎和扩张性心肌病心肌中β-sarcoglycan的免疫组化染色观察

目的探讨病毒性心肌炎(viralmyocarditis,VCM)和扩张型心肌病(dilatedcardiomyopathy,DCM)的发病机制及相互关系,从而提高心性猝死法医学鉴定的可靠性和准确性。方法对17例对照组(包括冠心病、高血压性心脏病和正常心脏等),25例VCM和28例DCM的心肌组织进行改良的β-sarcoglycan免疫组织化学染色观察,并对其阳性反应率进行χ2检验及相关分析。结果β-SG蛋白在对照组,VCM组和DCM组中阳性反应率分别为100%,80%,46.4%。经χ2检验,3组阳性反应率差异有显著性意义(P<0.05);用χ2分割法分析,VCM和DCM组间差异有显著意义(P<0.05),且Spearman等级相关分析呈显著负相关(rs=-0.605)。结论病毒性心肌炎和扩张性心肌病病变与β-SG的被破坏有关;随着VCM病变程度的加重,其可能发展为DCM。     

Subvalvular aortic stenosis as a cause of sudden death: two case reports

Sudden death is defined as a death that occurs suddenly, develops during an unpredictable course, and is due to natural or unnatural causes. Although there is no universally standardized definition on how "sudden" a sudden death is, WHO defines sudden death as a death that occurs within 24 hours after the onset of symptoms. The aim of this study is to present 2 rarely reported autopsy cases and to emphasize the importance of systemic autopsy at sudden death. On macroscopic examination, crescent-shaped, thick, fibrous membranes, located 5 mm and 3 mm away from the aortic valves, were detected. Fibrous membranes extended from the ventricular septum to the left ventricular outflow tract, thus apparently narrowing this region. Left ventricular wall and septum were slightly thickened, and there were scattered grayish-white areas of a small diameter. These became more intense in the septum and myocardium of the left ventricle on the anterior plane of the myocardial sections. In both cases, the aortic valves of were thickened and also markedly narrowed on one of them. In this case, the fibrous membrane adhered to the aortic valve and extended to the anterior leaflet of the mitral valve at one side. Both aortic valves comprised 3 leaflets. Other valves and coronary arteries showed no macroscopic pathologic findings. Microscopic examination of both cases demonstrated that the fibrous membrane comprising abundant collagen fibers was situated on the ventricular septum. Hypertrophy, moderate to severe interstitial fibrosis, and focal areas of scarring were observed in the specimens taken from the septal and ventricular myocardium. No abnormality was found on the conduction system examinations. Toxicologic analysis results in blood were negative. Based on the findings, membranous-type (discrete type) subvalvular aortic stenosis, diagnosed during the autopsy, was considered as the cause of sudden death in both cases.     

Beta-hydroxybutyric acid--an indicator for an alcoholic ketoacidosis as cause of death in deceased alcohol abusers

We analyzed the postmortem blood of a total of 100 fatal cases for beta-hydroxybutyric acid (BHBA). In 25 cases of sudden and unexpected death of alcoholics we found pathologically increased levels of BHBA of 1260 to 47200 (median 8000) micromol/L. This led us to the diagnosis of an alcoholic ketoacidosis (AKA) as cause of death in these cases. The control group of 69 postmortem cases revealed that BHBA concentrations below 500 can be regarded as normal, and values up to 2500 micromol/L as elevated. Our study shows that BHBA values over 2500 micromol/L could lead to death, if no medical attention is sought. During storage we did not find any indication of postmortem formation or decomposition of BHBA in blood in vitro or in the corpses. In our opinion, BHBA should be considered the diagnostic marker of choice for the postmortem determination of alcoholic ketoacidosis (AKA) as the cause of death. The classical indications of such deaths are: unexpected death of a chronic alcoholic; none or only traces of ethanol in the blood; increased acetone blood concentration; and neither autopsy, histology, microbiology, nor toxicology reveal the cause of death. In six further cases a diabetic ketoacidosis (DKA) was diagnosed as the cause of death.     

Myocardial dysplasia of the right ventricle (Uhl's anomaly) as a possible cause of sudden, unexpected death

Partial absence and fatty replacement of the myocardial compacta of the right ventricular wall was observed in five young male adults, four of whom died suddenly and unexpectedly and one in a car accident. In one of these cases there was only one coronary orifice. Four cases of the so-called Uhl anomaly had histological findings indicating dysmorphic myocardial cells associated with minimal lymphohistiocytic infiltrates within the fatty tissue. In one case, chronic destructive inflammation was a prominent feature. Marked dysmorphic alterations in the myocardial fibers suggested the occurrence of arrhythmic episodes as the main cause of sudden heart failure and death.     

心肌病猝死者心肌连接蛋白43的免疫组化染色观察

目的探讨心肌病猝死者心肌连接蛋白43(Cx43)染色变化及其与猝死的关系。方法运用免疫组化和图像分析技术,分2组(A和B组)检测20例心肌病猝死者心室肌的Cx43染色情况;并与14例非心肌病猝死者(C组)的检测结果对照。结果扩张型心肌病(DCM)猝死组(A组,11例)心肌Cx43染色明显减弱,阳性着色斑点大小不等、深浅不一、分布不均,有的呈散在颗粒状;其它类型的心肌病猝死组(B组,9例)亦见类似变化;非心肌病猝死的对照组(C组,14例)未见明显变化。定量检测并经统计分析发现,Cx43蛋白染色阳性的面积,A组与B组和C组的差异有非常显著性意义(P<0.01),B组与C组的差异无显著性意义(P>0.05);而平均光密度各组之间的差异无显著性意义(P>0.05)。结论心肌病猝死者心肌Cx43免疫组化染色明显减弱,尤以扩张型心肌病明显;心肌病猝死者心肌Cx43变化可能与其猝死有一定关系。     

Presence of psychoactive substances in oral fluid from randomly selected drivers in Denmark

The aim of this investigation was to identify and characterise pathogenic mutations in a sudden cardiac death (SCD) cohort suspected of cardiomyopathy in persons aged 0-40 years. The study material for the genetic screening of cardiomyopathies consisted of 41 cases and was selected from the case database at the Institute of Forensic Medicine. Mutational screening by DNA sequencing was performed to detect mutations in DNA samples from deceased persons suspected of suffering from hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricle cardiomyopathy (ARVC). A total of 9 of the examined 41 cases had a rare sequence variant in the MYBPC3, MYH7, LMNA, PKP2 or TMEM43 genes, of which 4 cases (9.8%) were presumed to be pathogenic mutations. The presumed pathogenic mutations were distributed with one case of suspected HCM and DCM (MYH7; p.R442H), one case of suspected DCM (LMNA; p.R471H), and two cases of suspected ARVC (PKP2; p.R79X and LMNA; p.R644C). The presented data adds important information on the genetic elements of SCD in the young, and calls for expert pathological evaluation and molecular autopsy in the post-mortem examination of SCD victims with structural anomalies of the heart.     

Sudden death due to right ventricular cardiomyopathy

A 21-year-old man died suddenly at a small party. He had had no clinical signs of cardiac disease except for a slightly abnormal electrocardiogram (occasional premature ventricular contractions) since he was 15 years of age. Autopsy examination revealed cardiomegaly (469 g), with right atrial and ventricular dilatation. The right ventricular myocardium was massively replaced with adipose tissue, and there was one isolated fatty lesion in the right side of the ventricular septum. There were no congenital malformations such as a septal defect or valvular deformity. Histologically, muscular fibers remaining in the right ventricular wall showed neither degenerative nor inflammatory changes. An isolated lesion of the ventricular septum consisted of almost complete replacement of the muscle bundles with adipose tissue. Such a pathologic condition has recently been termed right ventricular cardiomyopathy. Postmortem examination is necessary to make a definite diagnosis of the disease, because in most adult cases of the disease, sudden death occurs before there have been any critical signs.     

Validation of diagnoses on death certificates for male alcoholics in Stockholm

The mortality and the causes of death have been studied in a cohort consisting of 1548 male alcoholics in Stockholm. During the period 1969-1981 there were 542 cases of death in this population. The mortality rates were triple those for males in Stockholm generally. Using the official causes of death there was a highly significant excess mortality in the following diagnostic groups: Cancer in the upper digestive region, primary hepatic cancer, cirrhosis in the liver, pancreatitis, pneumonia, alcoholism and alcoholic poisoning, suicides and other causes of violent death as well as ischemic heart disease. The underlying and contributing causes of death on the death certificates were reclassified according to ICD-rules using clinical records and autopsy protocols. It was found that the underlying cause of death was incorrect in 21.8% of the cases. Important information was withheld in further 19.8%. After validation there was no longer any excess mortality in ischemic heart disease. The number of alcohol-related diagnoses, i.e. alcoholic cardiomyopathy, cirrhosis and fatty liver with alcoholism and alcoholic intoxication, was much greater. It is concluded that there is a underreporting of alcohol-related diseases and injuries which has a great influence on the reliability of death statistics.     

Lympho-monocytic enteroviral myocarditis: traditional, immunohistological and molecularpathological methods for diagnosis in a case of suspected sudden infant death syndrome (SIDS)

A 7-month-old boy was found lifeless in his bed by his grandfather. Near the mouth there were some blood and chyme on the bedlinen. His mother reported a chill during the last 8 days. Autopsy revealed multiple petechia under the capsule of the thymus, subepicardially and subpleurally, the cause of death was tentative supposed to be a sudden infant death. Histologically parts of the myocardium showed a lympho-monocytic myocarditis according to the DALLAS-criteria. Immunohistological investigations demonstrated an enhanced expression of MHC class II antigens, an increased number of leucocytes as well as T-lymphocytes. In situ hybridization and immunohistochemistry revealed myocardial enterovirus infection. Considering that there were regions in the myocardium without the traditional findings of myocardial necrosis and inflammation but with distinct expression of the above mentioned immunohistologic markers, immunohistological investigations turn out to be an appropriate tool to examine infant fatalities with uncertain cause of death for early stages of myocarditis.     

原发性心肌病猝死心肌mtDNA~(4977)缺失变化

目的探讨原发性心肌病(PCM)猝死者心肌线粒体DNA(m tDNA4977)缺失情况及其与猝死的关系。方法对18例PCM猝死和28例对照组病例心肌组织蜡块,用常规方法提取心肌m tDNA,以PCR、琼脂糖紫外凝胶成像技术确定扩增产物激光密度,初步定量检测m tDNA4977缺失率。结果PCM猝死18例中,检见13例m tDNA4977缺失,占72.44%。对照组28例中,检见3例m tDNA4977缺失,占10.71%;两组病例m tDNA4977缺失率均值分别为0.5795和0.0744,差异有非常显著性意义。结论多数PCM,特别是扩张型心肌病猝死者心肌可检见m tDNA4977缺失;提示其心肌m tDNA4977缺失变化与PCM猝死的发生可能有一定关系。     

The diagnostic value of determining the level of acetaldehyde in blood,urine, and cerebrospinal fluid

The contents of acetaldehyde (AA) in biological fluids obtained from the dead with the confirmed lethality causes, i.e. ischemic heart disease (IHD), alcoholic cardiomyopathy (ACMP) and mechanical traumas (MT), were examined on an actual forensic-medical material (AFMM). 14 death cases of males, aged 18 to 45, were studied. The method of gas-liquid chromatography (GLC), or rather its variation of vaporphase analysis, was used to state the presence and to assess the concentration of acetaldehyde. The results revealed differences between concentrations of acetaldehyde in the examined groups depending on the presence or absence of alcoholemia. Thus, the AA concentrations were found in trace quantities in the MT group free of alcoholic intoxication; while, when it was present in this group, the concentrations went up several-fold. A higher AA content was typical of the ACMP group in all examined subjects both with and without alcoholic intoxication. The final study results are suggestive of that the AA determination in blood, urine and liquor by GLC could be used, within the forensic medical practice, in assessing a severity degree of alcoholic intoxication while establishing the lethal outcome cause due to chronic pathologies and MT.