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.     

Is there progress in the autopsy diagnosis of sudden unexpected death in adults?

Sudden death is now currently described as natural unexpected death occurring within 1h of new symptoms. Most studies on the subject focused on cardiac causes of death because most of the cases are related to cardiovascular disease, especially coronary artery disease. The incidence of sudden death varies largely as a function of coronary heart disease prevalence and is underestimated. Although cardiac causes are the leading cause of sudden death, the exact incidence of the other causes is not well established because in some countries, many sudden deaths are not autopsied. Many risk factors of sudden cardiac death are identified: age, gender, heredity factors such as malignant mutations, left ventricular hypertrophy and left ventricle function impairment. The role of the police surgeon in the investigation of sudden death is very important. This investigation requires the interrogation of witnesses and of the family members of the deceased. The interrogation of physicians of the rescue team who attempted resuscitation is also useful. Recent symptoms before death and past medical history must be searched. Other sudden deaths in the family must be noted. The distinction between sudden death at rest and during effort is very important because some lethal arrhythmia are triggered by catecholamines during stressful activity. The type of drugs taken by the deceased may indicate a particular disease linked with sudden death. Sudden death in the young always requires systematic forensic autopsy performed by at least one forensic pathologist. According to recent autopsy studies, coronary artery disease is still the major cause of death in people aged more than 35 years. Cardiomyopathies are more frequently encountered in people aged less than 35 years. The most frequent cardiomyopathy revealed by sudden death is now arrhythmogenic right ventricular cardiomyopathy also known simply as right ventricular cardiomyopathy (RVC). The postmortem diagnosis of cardiomyopathies is very important because the family of the deceased will need counseling and the first-degree relatives may undergo a possible screening to prevent other sudden deaths. In each case of sudden death, one important duty of the forensic pathologist is to inform the family of all autopsy results within 1 month after the autopsy. Most of the recent progress in autopsy diagnosis of sudden unexpected death in the adults comes from molecular biology, especially in case of sudden death without significant morphological anomalies. Searching mutations linked with functional cardiac pathology such as long-QT syndrome, Brugada syndrome or idiopathic ventricular fibrillation is now the best way in order to explain such sudden death. Moreover, new syndromes have been described by cardiologists, such as short-QT syndrome and revealed in some cases by a sudden death. Molecular biology is now needed when limits of morphological diagnosis have been reached.     

Staphylococcal scalded skin syndrome mimicking child abuse by burning

Determining the cause for the sudden death in young adults tends to be complex and difficult. Two cases of death of young people were autoptically investigated who died suddenly while carrying out their hobbies (a 22-year-old male musician and a 20-year-old female dancer). In both cases neither the police investigation, the autopsy, nor the toxicological investigations gave any relevant results. However, when investigating the histology fatty and fibrotic tissue in the right ventricle of the myocardium were found, whereas the myocytes proved to be degenerated--typical for arrhythmogenic right ventricular cardiomyopathy (ARVC). It is important to consider the possibility of heart rhythm failure if a clear reason for sudden death in young adults cannot be detected. Heart rhythm failure often involves the genetic background of the case, which suggests that genetic analysis should be carried out as a supportive means of diagnostics.     

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.     

Identification of Arrhythmogenic Right Ventricular Cardiomyopathy‐Causing Gene Mutations in Young Sudden Unexpected Death Autopsy Cases

Arrhythmogenic right ventricular cardiomyopathy (ARVC) results in an increased risk of sudden death. We sought mutations of desmoglein‐2 (DSG2), desmoplakin (DSP), and plakophilin‐2 (PKP2) in 15 cases of sudden death whose causes of death could not be determined at autopsy. In three victims, mutations were identified in DSP. Two of these mutations were novel; one had previously been reported in a patient with ARVC that had been diagnosed clinically. Histological findings were not typical of ARVC; however, it was notable that these mutations were present in three of 15 cases, a relatively high proportion. The causal relationship between the mutations and ARVC is unclear, but the mutations might have been associated with faulty desmosomal proteins resulting in fatal arrhythmia. Combining information gathered by the traditional means of gross and histological examination with postmortem genetic analysis of young victims would assist in identifying their cause of death.     

Sudden Death Caused by Anomalous Origin of the Coronary Artery During Exercise

Anomalous origin of the coronary artery (AOCA) is a rare, but important cause of sudden cardiac death among young athletes. Nine autopsy cases (8 male, 1 female; mean age, 17.9 years; age range, 11–31 years) of sudden death during or just after exercise caused by AOCA were reviewed. The exercises performed at the time of death were running (4 cases), soccer (2 cases), and baseball, swimming and kendo (Japanese swordsmanship) (1 case each). In 6 cases, the left coronary artery arose from the right sinus of Valsalva, and in 3, the right coronary artery from the left sinus. The coronary arteries passed between the pulmonary artery and the aorta with an acute angle takeoff from the orifice. Three cases had cardiovascular manifestations prior to death. In cases with cardiovascular manifestations, novel imaging methods should be considered to prevent sudden death.     

Stressful events as a trigger of sudden death: a study of 43 medico-legal autopsy cases

The reports relating emotional stress to sudden death are largely anecdotal. In addition to experimental and electrophysiological studies, an opportunity for a better understanding of possible stress-related sudden death (SSD) may be provided by medico-legal autopsies. The goal of our autopsy study was to analyze cardiovascular pathologic findings in cases of SSD and if possible identify mechanisms by which the stressful event (SE) could be the cause. Forty three cases were studied (29 males and 14 females). In all cases, the SE and the death were witnessed. The age range was 22 to 90 years in males (mean, 52) and 30 to 92 years in females (mean, 64). Death occurred in all cases without premonitory symptoms. In 20 cases, death occurred during the SE and in the other 23 cases occurred within 2 h of the event. SE included fear, 15 cases; altercation, 21 cases; sexual activity, 3 cases; police questioning or arrest, 4 cases. According to police reports, in 40 cases (90%), the victims had no previous clinical history of cardiovascular disease. At autopsy, the heart weight in males ranged from 255 to 1000 g with a mean of 517 g and in females the range was 250–700 g with a mean of 417 g. In only 3 cases, gross and microscopic examination of the heart was normal. In 2 of the remaining 40 cases the subjects died of subarachnoid hemorrhage. In 38 cases, a cardiac cause of death was found as follows: coronary heart disease, 27 cases; cardiomyopathy, 6 cases; aortic valvular stenosis, 2 cases and right ventricular dysplasia, 3 cases. A coronary artery thrombosis was found in 8 cases of sudden coronary death. Post myocardial infarction fibrosis was present in 25 cases (92%) of sudden coronary death. In conclusion, it appears from our autopsy study that SSD occurs primarily in those individuals with severe heart disease, especially coronary heart disease.     

Sudden infant death with anomalous origin of the left coronary artery.

Autopsy of a 3-month-old girl, an apparent case of sudden infant death syndrome, revealed anomalous origin of the left coronary artery from the right aortic sinus. Acute angulation of the left coronary artery along the aortic root, as well as a focal intramyocardial course within the ventricular septum, may have contributed to episodic luminal narrowing. Anomalous coronary origins of similar type have been associated with sudden death in children, teenagers, and young adults, but have not necessarily been associated with sudden death in older adults. Somewhat similar malformations have been reported in sudden infant death; two cases involved the left coronary artery and six involved the right.     

Sudden Cardiac Death in a Young Man with Migraine-associated Arrhythmia

A 31-year-old man with migraine-induced syncope and bradycardia with subsequent pacemaker implantation died unexpectedly. Clinically unsuspected cardiac anomalies were found at autopsy including myocardial bridging of the left anterior descending artery and shelf-like coronary artery ostia. Nortriptyline was identified by toxicologic analysis. A review of the autopsy findings, the historical information, and the effects of the possible arrhythmogenic circumstances is undertaken and the potential contributions to the death are discussed. Cardiac arrhythmias have been documented during migraines. Coronary artery bridging has been known to lead to ischemia and infarction, ventricular tachycardia, and sudden death; however, these are very rare sequelae. Congenital coronary artery anomalies have been linked to sudden cardiac death, but only rarely cause death in people younger than 31 years. Migraines and the autopsy findings described have been associated with cardiac arrhythmia and sudden death. Altogether, they led to the unexpected death of this young man.     

Arrhythmogenic right ventricular dysplasia cases in forensic autopsies

Arrhythmogenic right ventricular dysplasia or cardiomyopathy (ARVD or ARVC) is an increasingly recognized entity with clinical and forensic implications. This is the first series documenting ARVD in 5 separate cases in forensic autopsies from Turkey declared as natural sudden cardiac death following complete autopsy and toxicologic analysis. There was a male preponderance (M/F=4), with a mean age of 50.     

Sudden death in infancy due to bicuspid aortic valve

Symptoms of bicuspid aortic valve usually occur in the age group of 50-70 years, but rarely, it can also lead to sudden unexpected death in infancy and early childhood. The autopsy of a 2-month-old baby boy, found dead in his cot, revealed the heart weight as 25 g, and the macroscopic examination showed the circumference of the aortic valve consisting of two leaflets as 8 mm. The thickness of the left ventricle, right ventricle, and septum was measured as 8, 7, and 10 mm, respectively. Microscopically, the heart revealed hypertrophic changes of myocytes. Subendocardial areas displayed necrosis of myocytes, and severe and diffuse ischemic changes characterized by loss of myofibers and vacuolization. Interstitial pneumonia was identified in the lungs. Death occurred as a result of a congenital bicuspid aortic valve obstructing the left ventricular outflow tract complicated by lung infection. As there are only a few reported cases in infancy, and congenital bicuspid aortic valve can lead to sudden unexpected death, this case is presented to the forensic community.     

Cardiac rupture due to severe fatty infiltration in the right ventricular wall

An extremely rare case of sudden death caused by cardiac rupture due to severe fatty infiltration in the right ventricular myocardium is presented. The patient, a 74-year-old woman, had no history of chest trauma, hypertension, or pulmonary disease. The autopsy showed a small tear in the right ventricle and cardiac tamponade, but no coronary artery lesion. In the right ventricular myocardium, muscle fibers were definitely atrophic or absent, with massive fatty replacement. Fatty infiltration of the myocardium, if severe, can be a cause of serious cardiac dysfunction or, occasionally, sudden death.     

Evaluation of diagnostic tools applied in the examination of sudden unexpected deaths in infancy and early childhood

During the period between 1984 and 1999, 309 cases of sudden unexpected death in infancy and early childhood (0-3 years) were investigated at the Institute of Forensic Medicine in Oslo. In 73 cases, an explainable cause of death was found. In this non-sudden infant death syndrome (SIDS) group, 42 cases were due to disease, 14 to accidents, 7 to neglect/abuse and 10 cases were due to homicide. In 43 cases, there were pathological findings at the autopsy or suspect features in the history and/or circumstances, which were, however, insufficient to explain death ("borderline" SIDS). In the remaining 193 cases, nothing of significance was detected ("pure" SIDS).The purpose of the present study was to evaluate the importance of the different diagnostic tools used in diagnosing non-SIDS and borderline SIDS cases. The definition of SIDS requires a negative history as well as a negative autopsy result. Thus, the following variables were analysed: circumstances, medical history and autopsy, which included a gross pathological investigation, histology, neuropathology, microbiology, radiology and toxicology. In diagnosing deaths due to disease, histology, neuropathology and microbiology were the most important diagnostic tools. In contrast, information about the circumstances of death and the gross pathological findings at autopsy most often revealed the cause of death in accidents and cases of neglect/abuse and homicide.Following the drop in SIDS rate in Norway after 1989, the share of pure SIDS in proportion to the total population of sudden unexpected deaths in infancy and early childhood has decreased. The increasing proportion of non-SIDS and borderline SIDS cases presents a challenge to improve the quality of the investigation in cases of sudden death in infancy and early childhood.     

Causes of Sudden Death in Patients with Obstructive Sleep Apnea

There are few autopsy studies of patients dying suddenly with obstructive sleep apnea (OSA). Twenty‐five forensic autopsies of unexpected sudden death in individuals with OSA were reviewed. The causes of death were as follows: cardiomyopathy (n = 11); sudden unexpected death without morphologic findings (SUDNA, n = 6); and other cardiovascular diseases not related to OSA (n = 8). The cardiomyopathy group comprised five hearts with concentric left ventricular hypertrophy without dilatation and six with left ventricular diameter >4 cm (dilated cardiomyopathy). Four of six hearts in the SUDNA group showed right ventricular dilatation compared with seven of 11 showed cardiomyopathy and one of eight miscellaneous. The degree of obesity was greatest in the dilated cardiomyopathy group (10 of 11 obese) followed by the SUDNA group (four of six obese). The cardiac findings in patients dying suddenly and unexpectedly with OSA include nonspecific cardiomyopathy, other cardiac conditions, and hearts without a morphologic cause of death, which show frequent right ventricular dilatation as the only finding.     

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.     

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.     

Prothrombin G20210A mutation and sudden death

The authors present a case of sudden death in a previously healthy 36-year-old male. At autopsy there were bilateral pulmonary thromboemboli and right ventricular dilatation. Histologic findings in the lungs included recanalized, old thrombi and evidence of pulmonary hypertension. Genetic analysis for hereditary risk factors was heterozygous positive for the prothrombin G20210A mutation. Implications of this finding, its history and the diagnostic technique shall be discussed. The authors recommend that all cases of deep venous thromboses and pulmonary thromboemboli lacking known risk factors be evaluated for newly described genetic variations associated with an increased risk for venous thrombosis.     

Blood strontium concentration related to the length of the agonal period in seawater drowning cases

The levels of ventricular blood strontium (Sr) from 70 seawater drowning victims were compared with their diagnosis of drowning based mainly on certain criteria selected from their autopsy report. From this comparison, intervals of either the difference of Sr concentration between the left and the right ventricle blood (LVSr-RVSr) or the Sr concentration in the left ventricle blood (LVSr), appear to be related to different time-lapses of the agonal period of drowning. In the aim to diagnose drownings, intervals of both LVSr-RVSr and LVSr were proposed to characterize three different agonal periods in seawater drowning cases: instantaneous death (ID), fast vital-submersion drowning (FVSD) and common vital-submersion drowning (CVSD).     

Sudden death in an adolescent four years after recovery from mucocutaneous lymph node syndrome (Kawasaki disease)

A case is presented of sudden death during physical activity in a 15-year-old boy with clinically inactive mucocutaneous lymph node syndrome (Kawasaki disease). At autopsy, the coronary arteries were involved by multiple aneurysms and obstructive thrombi, and the left ventricular myocardium was extensively scarred. Although Kawasaki disease most commonly occurs in infants and young children, it may be a cause of sudden death in adolescents.     

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.