Examination of the cardiac conduction system: forensic application in cases of sudden cardiac death

Forensic pathologists may occasionally encounter cases of apparent sudden cardiac death without gross cardiac abnormality. In some of these cases, evaluation of the cardiac conduction system may reveal pathologic lesions which may act as the substrates for ventricular tachyarrhythmias and sudden death. Sample case studies are used to illustrate the suggested criteria and techniques for examination, and commonly-encountered pathologic lesions and normal variants are discussed.     

An Unexpected Finding in SUDEP Involving a Child: Focal Myocardial Infarct Adjacent to Bundle of His

Sudden unexpected death in epilepsy (SUDEP) is a nontraumatic, nondrowning death of an individual with epilepsy in which an autopsy with appropriate ancillary studies does not identify a cause of death. The mechanism of death in SUDEP is unknown, but is thought to involve cardiac and/or respiratory mechanisms. Research in SUDEP is hindered by a lack of consensus regarding required components of a death investigation before a cause of death may be certified as SUDEP. Histopathologic examination of the cardiac conduction system is not routinely performed in SUDEP death investigations. We present a case of SUDEP where histopathologic examination of the cardiac conduction system revealed a focal myocardial infarct of the summit of the ventricular septum abutting the bundle of His, which potentially provides insight into the mechanism of SUDEP for this particular case, and suggests that routine examination of the cardiac conduction system in SUDEP may be beneficial.     

Sudden Death Due to Infiltration of Left Bundle Branches by Interventricular Septal Cardiac Fibroma

Cardiac fibromas are benign conditions; however, their location and size may cause ventricular arrhythmias and sudden cardiac death. We report a case of a 68‐year‐old female who died suddenly. Postmortem investigation detected a huge cardiac fibroma in the pars muscularis of the interventricular septum, occupying almost the entire muscular septum, and restricting the volume of left ventricular chamber. Histological examination revealed numerous foci of calcification in the alternating complex interlacing or strictly parallel collagenous fiber mass. Tumor mass was mainly demarcated, but in some places, fibrous infiltration of surrounding working cardiac muscle was found. We present a case when direct tumor involvement in the descending left bundle branches was evidenced. Mainly, the branches of septal fascicle were disrupted, entrapped, and degenerated by the tumor mass. This case report emphasizes that postmortem histological examination of conduction system in all sudden cardiac death cases may substantially improve the accuracy of postmortem diagnosis.     

急性心肌梗死心传导系统的免疫组化实验观察

观察急性心肌梗死时心传导系统的形态学改变。取急性心肌梗死死亡者的心传导系统标本6例,运用抗纤维连接蛋白抗体、肌红蛋白抗体、血管内皮生长因子抗体进行免疫组化染色。结果发现,纤维连接蛋白染色有3例呈现强阳性,2例出现阳性,1例出现弱阳性;血管内皮生长因子染色均呈弱阳性;肌红蛋白染色呈脱失改变。提示纤维连接蛋白检测量敏感性强,稳定性好,易于观察,可作为在心肌梗死时了解心传导系统受损害的指标之一。     

Sudden cardiac death in a young woman: tumor of the atrioventricular (AV) node or citalopram intoxication?

Atrioventricular (AV) node tumor is a very rare lesion of the cardiac conduction system. Clinically, it is associated with complete AV block and sudden cardiac death, often in apparently healthy young people.We report a case of a 24-year-old woman who developed ventricular fibrillation during sexual intercourse and died before admittance to the hospital. The woman had a medical history of depression and was treated with citalopram.At first, no macroscopic or microscopic pathologic changes were found. Toxicologic analysis showed a toxic level of citalopram in the blood. Further microscopic examination of the cardiac conduction system disclosed a tumor of the AV node. Immunohistochemical staining confirmed endodermal origin in accordance with the latest hypothesis of the pathogenesis of this tumor.It was concluded that this young woman died of cardiac arrhythmia due to the AV tumor and not from citalopram intoxication, as first suspected. This case emphasizes the importance of a microscopic examination of the cardiac conduction system in cases of sudden unexpected death, even in cases with a plausible cause and manner of death at first glance.     

Metastatic calcification of the cardiac conduction system with heart block: an under-reported entity in chronic renal failure patients

Systemic metastatic calcification is a common complication of chronic renal failure. Cardiac involvement is particularly ominous, especially when the cardiac conduction system is affected. Conduction defects, arrhythmias, and sudden death have all been reported with conduction system calcification; however, these are relatively under-reported or unrecognized causes of cardiac morbidity and mortality. We describe a 40-year-old man with Von Hippel-Lindau disease who had been maintained on hemodialysis for two years following bilateral nephrectomies for renal cell carcinoma. The patient presented with symptomatic complete heart block that had progressed from Mobitz type I atrioventricular block. Two months later, while being internally paced, the patient died unexpectedly after a complicated hospital admission. Postmortem revealed extensive vascular, myocardial, and conduction system calcification. Conduction system calcification may cause sudden death in chronic renal failure patients during hospital admission, or unexpectedly while the patient is in the community. Knowledge of this condition is necessary to detect it, as the conduction system is not routinely examined. A routine abbreviated conduction system examination is warranted for patients with systemic metastatic calcification, especially if they have sudden death or a known history of heart block.     

Verapamil toxicity: an unusual case report and review of the literature

Verapamil blocks the rapid influx of calcium into the cardiac myocytes of the cardiac conduction system and smooth muscle of the vasculature, resulting in decreased myocardial contractility, prolonged conduction time, and vascular relaxation. A sustained-release form, verapamil SR (or ER), is available that contains higher levels of medication and requires only once-daily dosing. The majority of reported fatal cases of verapamil toxicity are due to massive, intentional overdoses. Herein, we present an unusual case of fatal verapamil SR toxicity in a 57-year-old female that resulted from accidental overdose of only 3 tablets (720 mg), as witnessed by the decedent's daughter. In spite of the low dose ingested, the postmortem cardiac blood verapamil level was clearly toxic (6000 ng/mL, or 6 mg/L). Her preexisting medical conditions included hypercholesterolemia, hypertension, iron deficiency anemia, diabetes mellitus, and associated mild chronic renal failure. Complicating factors, which likely include the decedent's preexisting renal and cardiac disease, and a review of the available literature will be discussed.     

Toxicological aspects of fatal chloroquine poisoning over a period of several days

The anti-inflammatory and antimalarial drug chloroquine is said to be one of the most frequently used drugs to commit suicide in the Orient and Far East. After the ingestion of large amounts of this 4-amino-chinoline derivate, signs of cardiac conduction disturbances are evidence of cardiotoxic action. For clinical treatment, hemoperfusion by activated charcoal has rather than hemodialysis proved to be partly effective for the removal of the toxic substance. Following a suicidal overdose of chloroquine tablets in a 13-year-old boy, we could confirm the efficiency of hemoperfusion by continued toxicologic examinations. The total elimination was nevertheless slow. Due to high postmortem concentrations in the blood and tissues, we believe that chloroquine is deposited and especially concentrated in the reticulohistiocytary system of the liver. Death after 5 days of clinical treatment in this case may be referred to as the first cardiac arrest with irreversible hypoxic damage of the brain.     

心脏传导系统的增龄性变化

心脏传导系统（CCS）包括窦房结（SAN）、房室结（AVN）、房室束（又称希氏束，HB）、左右束支（LBB，RBB）及其终末纤维网，其功能是把心脏搏动的冲动传导到整个心脏，以协调心脏的节律性收缩．近年来，CCS病变与猝死的关系引起重视，已有研究表明，一些猝死与CCS的病变有关。但在实际应用中，必须将CCS增龄变化同其病变区分开来，以免误将其正常增龄变化视为病变，导致错误的结论．1SAN的年龄变化在光镜水平，Lev[1]首先对53例4个月胎儿至90岁老人的SAN进行了分年龄组观察；Davies[2]对50岁以下和75岁以上两组各50例的SAN…     

Sudden death related to small coronary artery disease

Two cases of sudden death of young people in apparently good health are reported. The only pathologic change found was a fibromuscular dysplasia of the artery supplying the conduction system of the heart with an important narrowing of the lumen and strong thickening of the arterial wall. The first case was of a 12-year-old girl who died suddenly while skiing; the second was of a 32-year-old man who died while talking to his wife. No other pathologic changes were found at autopsy, and the results of toxicologic analysis were negative. There was no individual or family history of cardiac diseases. These cases illustrate the importance of an analysis of the conduction system, including examination of the intramural coronary arteries supplying the conduction system.     

正常人心脏传导系统神经组织的免疫组化研究

作者应用抗Ｓ１００抗体，对１０例正常心脏传导系统的神经进行了免疫组化研究。结果显示：Ｓ１００阳性的神经组织在心脏传导系统内广泛分布，其含量以窦房结最多，房室结次之，希氏束和束支最少。该研究获得了正常人心脏传导系统神经组织分布的概貌，为进一步研究心脏传导系统神经组织病变与猝死的关系打下了基础。     

Morphological signs of impaired excitation conduction in the myocardium

The article describes morphological changes in cardiac muscular fibers and cardiomyocytes secondary to disorders in conduction of excitation in the myocardium. These changes may indicate cardiac arrest as a result of reflex impacts including cases of damage which is not lethal.     

Sudden unexplained death among persons 1-35 years old

Sudden unexplained death (SUD) on children and young people is unusual, although the real magnitude is unknown. The clinical and physiopathological characteristics are poorly defined. The aim of this work is to analyse the epidemiological, clinical and pathological characteristics of SUD on children and young people. In this population observational study, all sudden non-violent deaths between 1 and 35 years occurred in Bizkaia (north Spain) from 1991 to 1998 were investigated, analysing those diagnosed as SUD. Pathological records, circumstances of death and autopsy findings were obtained. Out of 107 cases of sudden death (SD), 19 were SUD. The mortality rate of SUD was 0.43/100,000 persons per year. Five had pathological antecedents: syncopal episodes in three cases and tachycardia and ventricular extrasystoles one each. The initial symptom was sudden collapse (N=13). In four cases, a precipitating factor was identified (two physical exercise and two emotional stress). Six cases died during sleep. Minimal pathological findings in coronary arteries, myocardium or conduction system was found in nine cases. Heart weight increased (under interval of confidence of 95%) was present in 12 cases. In conclusion, the SUD is very infrequent in children and young people. However, it has great clinical significance because it affects people in good health and occurs without warning symptoms. Some of these cases can be due to cardiac arrhythmias. In deaths in bed there is a high frequency of SUD. In the future, it may be possible that abnormalities at a molecular level will be detected in some of the cases identified today as SUD.     

Sudden death in mitral valve prolapse: Associated accessory atrioventricular pathways

Sudden death in patients with mitral valve prolapse is a rare complication with a possible arrhythmic mechanism. We made a detailed postmortem examination of the conduction system in three patients with MVP who died suddenly. One patient who died in cardiac failure had a normal conduction system. The two other patients with no cardiac symptoms prior to death had both accessory atrioventricular pathways.These findings suggest a higher incidence than hitherto known of accessory bypass tracts in patients with MVP who die suddenly, and support the presumption of an arrhythmic cause of death.     

Sudden death resulting from lesions of the cardiac conduction system

Sudden unexpected deaths in young persons with noncontributory histories, autopsy results, and drug screen results are a common problem in forensic pathology. As part of the evaluation of such cases, the cardiac conduction system (CCS) should be studied. To determine the type and incidence of lethal CCS lesions, the authors reviewed their files of sudden unexpected cardiac deaths with particular attention to cases with causes of death in the conduction system. Cases of sudden cardiac death in patients aged < or=40 years during a 10-year period (Michigan) and a 4 year-period (Spain) were selected from the files. From this group, cases were identified in which the cause of death was a lethal change in the CCS. The portions of the heart containing the CCS were excised, and at least one hematoxylin and eosin slide and at least one trichrome or elastic trichrome slide per block were studied. In the two centers, 381 cases of sudden cardiac death were identified. The most common causes of sudden cardiac death were arteriosclerotic narrowing of the coronary arteries, cardiomyopathy, and myocarditis. In 82 cases, there was no identifiable cause of death even after complete gross and microscopic autopsy was performed, a medical history was obtained, and a drug screen was performed. In 11 cases, the CCS contained lesions that were considered lethal: narrowing of the atrioventricular node artery by fibromuscular hyperplasia (7 cases) and atrioventricular node tumors (4 cases). The 11 cases accounted for 2.9% of the 381 cases of sudden cardiac death and 11.8% of the indeterminable cases. It was concluded that examination of the CCS in deaths in which the gross and microscopic autopsy, history, and drug screen fail to provide a cause of death can yield a cause of death in a significant percentage of cases. If heart block was not documented during life and no explanatory lesions were found during routine cardiac examination, examination of the CCS can yield valuable information.     

Congenital atrioventricular block: histological aspects

It is known that maternal immunological factors such as systemic disease are involved in the genesis of cardiac conduction problems in the fetus but the histologic changes in the conduction system are less documented. We report the case of a 33-year-old woman with no significant medical history. Her first pregnancy was induced by Clomifene. At 17 weeks of gestation, the fetus presented sonographic abnormalities characteristic of a complete atrioventricular block. Biological investigations found anti-SSA and -SSB antibodies. Clinical history search for systemic disease was positive for photosensitivity, lasting 10 years, suggesting the diagnosis of systemic lupus erythematosus. The patient was treated with prednisone 20 mg per day but fetal death occurred at 29 weeks of gestation. Histological examination of the fetal heart showed an altered atrioventricular node and bundle of His with fibrosis, calcifications, endocardial fibroelastosis and mononucleated inflammatory cells. The search for these specific lesions can be determinant in establishing the disease pathogenesis; also, it is important to eliminate this diagnosis in an unexplained fetal death.     

178例心源性猝死法医组织病理学诊断分析

目的探讨心源性猝死(SCD)的病理特点与鉴别要点。方法对四川华西法医学鉴定中心2000—2005年尸检出的178例SCD死亡案例进行回顾性分析,主要对其病因、年龄、诱因及病理改变进行分析。结果本组资料显示冠心病、心传导系统病变、心肌炎、心肌病等在SCD中占有较大比例。冠心病猝死是中老年人SCD的最主要原因,青壮年人SCD的病因以非冠心病为主。如传导系统病变、心肌炎、心肌病。在儿童的SCD中先天性心脏病、传导系统病变及心肌炎占主导地位。结论不同的病因,其病理特点不同,其病理变化是法医学鉴定的主要依据。     

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.     

Heart valve tissue donation does not preclude the diagnosis of clinically significant pediatric cardiac abnormalities

Medical examiners/coroners often have the responsibility of deciding whether to allow organ and tissue donation to proceed in cases under their jurisdiction. A 10-year retrospective study was conducted of autopsy cases in children younger than 6 years to determine whether the donation of cardiac valve tissue would preclude the diagnosis of clinically significant pediatric cardiac abnormalities. Only 1 case (0.1%) was found in the entire 10-year period in which valve tissue donation might have prevented the correct diagnosis. According to the results of the study, (1) most cardiac findings in forensic pediatric autopsies are not clinically significant; (2) clinically significant findings will be diagnosed in properly examined hearts, even those processed for valve tissue donation, and special studies will remain possible in nearly all hearts except those with suspicion of conduction defects; and (3) as long as there is good communication between forensic pathologists and organ and tissue procurement organizations, the concern of failing to diagnose significant cardiac findings should not inhibit medical examiners/coroners from allowing the donation of pediatric cardiac valve tissue.     

Poor results in attempting to demonstrate the cause of death by examination of the conduction system of the heart in cases of sudden death

A microscopic examination of the proximal part of the conduction system in the heart was undertaken in seven cases of sudden death due to coronary arteriosclerosis; the same technique was applied to 31 control cases. A few infiltrations of mononuclear cells were demonstrated in relation to the conduction system in cases of sudden death as well as in controls. In one case severe narrowing of the sinus node artery was found without particular arteriosclerosis of the coronary arteries.