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.     

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…     

Diagnostic value of post-mortem examination of the cardiac conduction system

Introduction (Aim)

Sudden unexplained death (SUD) is a common problem in forensic pathology. In many of these cases, the autopsy findings, toxicological examinations and patient history are inconclusive. Many studies suggest that in such cases, the cardiac conduction system (CCS) should be histologically examined. We decided to determine the diagnostic value of histological examination of the CCS.

Methods

We reviewed autopsy files from the period 2005–2007 and selected those cases in which the CCS had been sampled. These were divided into two groups, the first comprising cases with an obvious cardiac pathology (e.g. severe coronary disease, myocardial infarction, significant myocardial hypertrophy/dilatation, valvular disease, etc.) and the second comprising cases without obvious cardiac pathology (i.e. fatal injuries, intoxications and deaths unexplainable by routine procedures). The CCS was sampled according to a detailed protocol and examined under a light microscope. On the basis of the findings of histological examination of CCS, we formed subgroups of the aforementioned main groups.

Results

We analyzed 118 cases, of which 83 were males and 35 females. In 57% of cases, autopsy revealed gross pathological abnormalities of the heart. In 10 (15%) of them, examination of the CCS showed significant pathological changes (narrowing of the nodal artery and its branches, moderate to severe interstitial fibrosis, calcifications in the central fibrous body impinging upon CCS). In some, especially those with no acute findings, CCS disease can be considered to have been the cause of fatal arrhythmias. In 43% of cases, autopsy revealed no gross abnormalities of the heart, while histological examination of the CCS disclosed significant pathological changes in 4 (8%). Among them, CCS disease was regarded as the cause of death in one case and as a possible cause in another case.

Conclusion

As with other similar studies, our study showed that examination of the CCS can provide valuable information on the cause of death. We therefore consider that examination of the CCS should be performed in all SUD cases, especially those in which the cause of death cannot be established by routine procedures. Although we had only 1 confirmed cause of death linked to CCS disease and one possible, we had 14 cases with significant pathological CCS changes. This leads us to the conclusion that post-mortem examination of the CCS is of diagnostic value.     

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.     

886例人心传导系统形态变异研究

探讨划分心传导系统 (CCS)变异与发育异常的界限。用本组建立的CCS检查法[1] ,连续切片 ,HE或Masson三色染色 ,光镜检查 ,对非心源性死亡组 (737例 )和心源性猝死组 (14 9例 )进行形态学及死因对比分析。结果显示 :(1)人CCS具有大小、位置和形态的先天性变异 ;(2 ) 4例心源性猝死者的房室结、房室束发育异常。房室束分叉部向室间隔膜部内移位、偏向于室间隔左侧、向左下侧移位 ,以及不足 1/2房室结移位至中心纤维体内、普通心肌移位至房室束或左束支内等应属变异 ;成年人胎儿型房室结及房室结全部移位至中心纤维体内或房室束完全分成 3束以上 ,房室束分叉部移位至三尖瓣根部应视为发育异常     

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。     

青年人CCS脂肪超前变化致猝死

为研究心传导系统（CCS）与猝死的相互关系，对120例心性猝死者CCS作常规检查，光镜下作半定量计算其脂肪含量。结果发现：9例经一般常规尸检未找到任何致死原因的青年人（30岁以下），其房室结（AVN）与房室束（HB）的脂肪组织含量为70％，比同龄人明显增多，致使结、束肌细胞被脂肪分割中断或压迫萎缩。结内外细胞连接不足或缺失是构成心电不稳的病理基础。此外本文尚对其脂肪浸润的病因发病，猝死机理作了探讨。     

Abnormal heart rate response during newborn sucking behavior study: Subsequent sudden infant death syndrome with cardiac conduction abnormality

This report concerns a four-month-old white female infant who exhibited abnormal feeding behavior and EKG irregularities during a newborn sucking behavior study. The immediate post-birth history showed an irregular heart rate on two occasions, but a cardiac consultation elicited no unusual findings. During sucrose sucking conditions, the heart rate increased with a beat-to-beat variation of 50 beats per minute, noted to be due to premature atrial beats. At 39 days, an EKG showed a marked sinus tachycardia of 156, a PR interval of 0.08, QRS of 0.05 and a QT of 0.26. The infant was diagnosed as a sudden infant death syndrome (SIDS) following an unexpected death at home. Subsequent cardiac pathology revealed an anomalous tract between the right atrium and the atrioventricular (AV) bundle which formed an extensive bypass of the AV node (atrio-His tract), and two accessory AV connections between the left atrium and posterior left ventricle. These findings are consistent with the Wolff-Parkinson-White syndrome type A. Only further studies can determine whether such abnormal feeding behavior with EKG irregularities can be used to identify infants who are at high risk for sudden death.     

Pharmacokinetics of ethanol in patients with renal failure before and after hemodialysis

We studied the pharmacokinetics of ethanol in seven patients suffering from terminal renal failure before and after they underwent hemodialysis. Ethanol (0.40 g/kg) was administered in the morning after an overnight fast by a constant rate intravenous (IV) infusion over 45 min. After removing a mean fluid volume of 2.46±0.48 liters (±SD), span 1.76–3.43 liters by hemodialysis, the same subjects received a second IV infusion of ethanol after they had eaten lunch. At exactly timed intervals of 0, 45, 90, 105, 120, 135, 150, 165, and 180 min from the start of the infusion, two blood-samples were drawn and the plasma portion of one of them was obtained by centrifugation. The concentration of ethanol in blood and plasma was determined by headspace gas chromatography and the water-content of whole blood was determined from the change in weight after desiccation. Plasma always contained a higher concentration of ethanol than whole blood and the mean plasma/whole blood ratio in patients with renal failure was 1.07:1 (span 1.05–1.10). The rate of ethanol disappearance from blood (β-slope) was faster (0.185±0.013 versus 0.157±0.022 g/l/h), the C₀ value was higher (0.79±0.08 versus 0.73±0.10 g/l) and the apparent volume of distribution (V_d) of ethanol was lower (0.507±0.049 versus 0.558±0.078 l/kg) after hemodialysis. The water content of whole blood was significantly higher (P<0.001) before dialysis (88.6±1.97 g/100 ml) compared with after dialysis (87.4±2.01 g/100 ml). The higher V_d for ethanol and lower C₀ as well as higher blood-water content are to be expected for a over hydrated condition before hemodialysis. The swifter rate of ethanol elimination from blood (β-slope) after hemodialysis should be interpreted with caution because eating a meal before the second infusion of ethanol is a confounding factor. Nevertheless, the rate of elimination of ethanol from blood in patients with renal failure agreed reasonably well with values expected for healthy subjects, namely mean 0.15 g/l/h spanning from 0.10 to 0.20 g/l/h.     

26例心脏传导系统发育异常猝死的病理学分析

目的研究心脏传导系统发育异常致猝死的病理变化。方法排除外伤、中毒及疾病所致死亡,收集26例不明原因猝死者心脏,采用作者创建的心脏传导系统取材法,常规切片、HE染色和Masson三色染色,光镜观察。结果 26例中见心传导系统有发育不全、结构异常、细胞或组织结构移位和窦房结纤维垫等病变,9例同时具有2~3种类型。16~30岁共21例,占全部样本的80.8%。结论心脏传导系统发育异常可能是不明原因青壮年猝死的重要原因之一。     

Age-related variation in the interstitial tissues of the cardiac conduction system; and autopsy study of 230 Han Chinese

The amount of fatty and fibrous tissues in 230 Han Chinese who died of noncardio-vascular diseases has been studied by a semi-quantitative method and analysed by chi-square test. The results have shown some consistency. Generally, in the sino-atrial node (SAN), fibrosis and fatty influtratin appear only after 40 years of age and increase one grade with every 20 years. The atrio-ventricular node (AVN) showed fatty change after 30 years of age and fibrosis appeared after 60. In the His bundle (HB), fatty infiltration and fibrosis appear after 40 years. The left bundle branch (LBB) showed similar changes. The appearance of fibrosis in the AVN seems to be later than that reported by Lev.     

Cor triatriatum sinistrum: a rare congenital cardiac anomaly presenting in an adult with chronic atrial fibrillation

Cor triatriatum is a rare congenital cardiac anomaly in which the left atrium is divided into proximal (dorsal or upper) and distal (ventral or lower) chambers by a fibromuscular septum. The upper chamber receives the pulmonary veins and the lower chamber contains the atrial appendage and the mitral valve. The 2 chambers communicate through a defect in the membrane. Cor triatriatum is often associated with other congenital cardiac anomalies. Most frequently, the upper chamber communicates with the right atrium through a patent foramen ovale or atrial septal defect, and the clinical symptoms simulate anomalous pulmonary venous return. Less commonly, the foramen ovale communicates with the distal chamber and the clinical features mimic mitral stenosis. When cor triatriatum is the only abnormality, the clinical findings are also similar to mitral stenosis with development of pulmonary hypertension and subsequent right ventricular hypertrophy and atrial enlargement. The diagnosis is usually made in infancy or childhood, and the lack of treatment results in death in 75% of patients.We report the case of a woman who presented much later in life. The patient was a 57-year-old female with a clinical history of chronic atrial fibrillation who presented to the emergency department because of a "funny sensation" in her chest, though she denied chest pain, nausea, vomiting, or diaphoresis. EKG revealed atrial fibrillation with a rapid ventricular response and a tachycardic rate of 157. She had a therapeutic level of digoxin, and cardiac enzymes were normal. The patient was admitted and placed on Cardizem drip. Serial EKGs remained normal and heart rate control was achieved. On hospital day 2, the patient became dyspneic and cyanotic. She went into cardiac arrest and died.Autopsy revealed cardiomegaly (610 g) with 4-chamber dilatation. A septum divided the left atrium into 2 chambers. The defect in the dividing membrane measured 1 cm in diameter. No other congenital defects were noted. The large size of the defect in the membrane likely accounted for the late onset of symptoms that allowed this patient to survive into adulthood without previous diagnosis or surgical intervention (which is usually required in childhood).     

Sudden death following exercise testing related to abnormalities of the cardiac conduction system and coronary artery pathology

A case of sudden death following exercise testing in a 33-year-old man is reported. The forensic autopsy showed atherosclerotic stenosis of the left coronary artery, as well as some changes in the cardiac conduction system, including anomalies of the atrioventricular node and moderate fibrosis and fatty infiltration of the branching bundle. This case demonstrates that cardiac arrest during vigorous exercise may be multifactorial and that abnormalities of the cardiac conduction system may have played some role in the fatal issue.     

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.     

一例急性肾衰竭合并脑梗死的抢救及护理体会

急性肾衰竭合并脑梗死患者病情危重,常易发生呼吸、循环衰竭而导致生命危险,及时、有效地抢救和护理是提高病人存活率的重要条件.     

Evaluation of a simplified method of the conduction system analysis in 110 forensic cases

A simplified method of the His bundle analysis is evaluated by the study of 110 forensic cases. The atrioventricular node or its part were observed in 96 cases (87.3%), penetrating bundle in 92 cases (83.6%), branching and left bundles branch in 109 cases (99.1%) and right bundle branch in 73 cases (66.4%). The changes such as fibrosis and fatty infiltration show statistically significant differences (P<0.01) between progressive age groups confirming their degenerative and age-related nature. The study included as well nine cases of sudden unexpected death and two cases of sudden infant death syndrome (SIDS), for which the autopsy with histological examination and toxicological analysis resulted negative. For nine of these cases, pathological lesions were found which can even explain the fatal issue. Moreover, in the cases with known cause of death, potentially lethal changes were noticed. This simple, low cost technique could be proposed to forensic pathologists as easy to fit into the routine processing of autopsy material, allowing the detection of major abnormalities with minimal effort. The authors also consider the difficulties related to the interpretation of the pathological findings in the conduction system.     

Functional morphology of the hypothalamo-hypophyseal-adrenal system in acute coronary failure]

Histological and morphometric studies of large-cell and small-cell hypothalamic nuclei, adenohypophysis, and adrenal cortex of patients who died from acute coronary failure revealed signs of persistent hyperfunction of small-cell nuclei of the hypothalamus, bundle and retinal adrenocortical zones, and signs of short-term hyperfunction of pituitary adenocytes. These changes indicate disorders in the hypothalamic regulation of adrenal activity.     

心肌及传导组织内3种蛋白的变化与SMDS的相关性

目的 观察心肌及传导组织内肌动蛋白、血浆白蛋白及纤维连接蛋白的染色变化，探讨青壮年猝死综合征(SMDS)死后诊断的新方法。方法 应用免疫组化S-P法，对SMDS及冠心病猝死者心肌及传导系统内肌动蛋白、血浆白蛋白和纤维连接蛋白的进行染色观察。结果 22例SMDS例猝死者心肌及传导系统内的肌动蛋白缺染17例；血浆白蛋白染色阳性18例；纤维连接蛋白染色阳性15例。并发现在SMDS中，8例有CCS严重病变。结论 心肌及传导系统内血浆蛋白、肌动蛋白改变与SMDS密切相关，部分SMDS病例死前存在早期心肌缺血或梗死的改变。