RESUMO
Sudden cardiac death (SCD) in a young athlete represents a dramatic event, and an increasing number of medico-legal cases have addressed this topic. In addition to representing an ethical and medico-legal responsibility, prevention of SCD is directly correlated with accurate eligibility/disqualification decisions, with an inappropriate pronouncement in either direction potentially leading to legal controversy. This review summarizes the common causes of SCD in young athletes, divided into structural (hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, congenital coronary artery anomalies, etc.), electrical (Brugada, congenital LQT, Wolf-Parkinson-White syndrome, etc.), and acquired cardiac abnormalities (myocarditis, etc.). In addition, the roles of hereditary cardiac anomalies in SCD in athletes and the effects of a positive result on them and their families are discussed. The medico-legal relevance of pre-participation screening is analyzed, and recommendations from the American Heart Association and European Society of Cardiology are compared. Finally, the main issues concerning the differentiation between physiologic cardiac adaptation in athletes and pathologic findings and, thereby, definition of the so-called gray zone, which is based on exact knowledge of the mechanism of cardiac remodeling including structural or functional adaptions, will be addressed.
Assuntos
Atletas , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Ecocardiografia , Eletrocardiografia , Cardiopatias/complicações , Cardiopatias/genética , Cardiopatias/patologia , Humanos , Consentimento Livre e Esclarecido/legislação & jurisprudência , Responsabilidade Legal , Programas de Rastreamento/legislação & jurisprudência , Anamnese , Exame Físico , Guias de Prática Clínica como Assunto , Medição de RiscoRESUMO
Sudden unexpected death in epilepsy (SUDEP) is defined as the abrupt, no traumatic, witnessed or unwitnessed death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus (seizure duration ≥ 30 min or seizures without recovery), and in which postmortem examination does not reveal a cause of death. Although the physiopathological mechanisms that underlie SUDEP remain to be clarified, the genetic background has been described to play a role in this disorder. Pathogenic variants in genes associated with epilepsy and encoding cardiac ion channels could explain the SUDEP phenotype. To test this we use the next-generation sequencing technology to sequence a cohort of SUDEP cases and its translation into clinical and forensic fields. A panel target resequencing was used to study 14 SUDEP cases from both postmortem (2 cases) and from living patients (12 cases). Genes already associated with SUDEP and also candidate genes had been investigated. Overall, 24 rare genetic variants were identified in 13 SUDEP cases. Four cases showed rare variants with complete segregation in the SCN1A, FBN1, HCN1, SCN4A, and EFHC1 genes, and one case with a rare variant in KCNQ1 gene showed incomplete pattern of inheritance. In four cases, rare variants were detected in CACNA1A, SCN11A and SCN10A, and KCNQ1 genes, but familial segregation was not possible due to lack of DNA from relatives. Finally, in the four remaining cases, the rare variants did not segregate in the family. This study confirms the link between epilepsy, sudden death, and cardiac disease. In addition, we identified new potential candidate genes for SUDEP: FBN1, HCN1, SCN4A, EFHC1, CACNA1A, SCN11A, and SCN10A. Further confirmation in larger cohorts will be necessary especially if genetic screening for SUDEP is applied to forensic and clinical medicine. Nevertheless, this study supports the emerging concept of a genetically determined cardiocerebral channelopathy.
Assuntos
Morte Súbita/etiologia , Epilepsia/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Adulto , Idoso , Proteínas de Ligação ao Cálcio/genética , Feminino , Fibrilina-1/genética , Genética Forense , Variação Genética , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canal de Potássio KCNQ1/genética , Masculino , Pessoa de Meia-Idade , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Linhagem , Canais de Potássio/genética , Adulto JovemRESUMO
Cocaine and alcohol toxicity is well known, especially when simultaneously abused. These drugs perform both acute and chronic harmfulness, with significant cardiac events such as ventricular arrhythmias, tachycardia, systemic hypertension, acute myocardial infarction, ventricular hypertrophy, and acute coronary syndrome. The present report refers about a patient who died after a documented episode of psychomotor agitation followed by cardiac arrest. At the autopsy investigation, arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed and confirmed by postmortem molecular analysis revealing a mutation in the DSG2 gene. Postmortem toxicological analysis demonstrated a recent intake of cocaine, and the death was attributed to cardiac arrhythmias. The detection of cocaine and cocaethylene in hair samples proved chronic simultaneous intake of cocaine and alcohol at least in the last month. The authors discuss the role of these drugs and genetic predisposition of the ARVC in causing the death of the patient.
Assuntos
Displasia Arritmogênica Ventricular Direita/genética , Depressores do Sistema Nervoso Central/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Morte Súbita Cardíaca/etiologia , Desmogleína 2/genética , Etanol/efeitos adversos , Mutação , Adulto , Displasia Arritmogênica Ventricular Direita/diagnóstico , Depressores do Sistema Nervoso Central/análise , Cocaína/análogos & derivados , Cocaína/análise , Eletrocardiografia , Etanol/análise , Toxicologia Forense , Cabelo/química , Parada Cardíaca/etiologia , Humanos , Masculino , Entorpecentes/análise , Taquicardia Sinusal/etiologiaRESUMO
Epilepsy affects approximately 3% of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24% of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy.
Assuntos
Arritmias Cardíacas/genética , Arritmias Cardíacas/mortalidade , Morte Súbita/epidemiologia , Morte Súbita/etiologia , Epilepsia/genética , Epilepsia/mortalidade , Genética Forense , Alelos , Síndrome de Brugada/genética , Síndrome de Brugada/mortalidade , Canalopatias/genética , Canalopatias/mortalidade , Códon sem Sentido/genética , Estudos de Coortes , Estudos Transversais , Análise Mutacional de DNA , Triagem de Portadores Genéticos , Testes Genéticos , Variação Genética/genética , Humanos , Incidência , Síndrome do QT Longo/genética , Síndrome do QT Longo/mortalidade , Mutação de Sentido Incorreto/genética , Análise de Sequência de DNARESUMO
Forensic medicine defines the unexplained sudden death as a death with a non-conclusive diagnosis after autopsy. Molecular diagnosis is being progressively incorporated in forensics, mainly due to improvement in genetics. New genetic technologies may help to identify the genetic cause of death, despite clinical interpretation of genetic data remains the current challenge. The identification of an inheritable defect responsible for arrhythmogenic syndromes could help to adopt preventive measures in family members, many of them asymptomatic but at risk of sudden death. This multidisciplinary translational research requires a specialized team.
Assuntos
Morte Súbita Cardíaca/etiologia , Arritmias Cardíacas/genética , Autopsia , Cardiomiopatias/genética , Canalopatias/genética , DNA/isolamento & purificação , Genética Forense , Testes Genéticos , Humanos , Anamnese , RNA Mensageiro/isolamento & purificação , Análise de Sequência de DNARESUMO
Arrhythmogenic right ventricular cardiomyopathy is a rare clinical entity characterised by fibro-fatty replacement of myocardium, mainly involving right ventricular free wall, leading to malignant electrical instability and sudden cardiac death. The disease is inherited in up to 50% of cases, with incomplete penetrance and variable phenotypic expression. To date, more than 300 pathogenic mutations have been identified in 12 genes, mainly with autosomal dominant inheritance. Here, we focus on recent advances in the genetics of arrhythmogenic right ventricular cardiomyopathy. Despite continuous improvements, current genotype-phenotype studies have not contributed yet to establish a genetic risk stratification of the disease.
Assuntos
Displasia Arritmogênica Ventricular Direita/genética , Desmossomos/genética , Predisposição Genética para Doença/genética , Genética Médica/métodos , Genética Médica/tendências , Fenótipo , Genes Dominantes/genética , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação/genética , Medição de Risco/métodosRESUMO
There has been increased interest in a possible association between epilepsy channelopathies and cardiac arrhythmias, such as long QT syndrome (LQTS). We report a kindred that features LQTS, idiopathic epilepsy, and increased risk of sudden death. Genetic study showed a previously unreported heterozygous point mutation (c.246T>C) in the KCNH2 gene. Functional studies showed that the mutation induces severe loss of function. This observation provides further evidence for a possible link between idiopathic epilepsy and LQTS.
Assuntos
Morte Súbita , Epilepsia/genética , Canais de Potássio Éter-A-Go-Go/genética , Saúde da Família , Síndrome do QT Longo/genética , Adolescente , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fenômenos Biofísicos/genética , Linhagem Celular Transformada , Análise Mutacional de DNA , Canal de Potássio ERG1 , Estimulação Elétrica , Eletrocardiografia , Epilepsia/complicações , Feminino , Humanos , Síndrome do QT Longo/complicações , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Técnicas de Patch-Clamp , Mutação Puntual/genética , Transfecção , Gêmeos Dizigóticos/genéticaRESUMO
The sudden death of a young person is a devastating event for both the family and community. Over the last decade, significant advances have been made in understanding both the clinical and genetic basis of sudden cardiac death. Many of the causes of sudden death are due to genetic heart disorders, which can lead to both structural (eg, hypertrophic cardiomyopathy) and arrhythmogenic abnormalities (eg, familial long QT syndrome, Brugada syndrome). Most commonly, sudden cardiac death can be the first presentation of an underlying heart problem, leaving the family at a loss as to why an otherwise healthy young person has died. Not only is this a tragic event for those involved, but it also presents a great challenge to the forensic pathologist involved in the management of the surviving family members. Evaluation of families requires a multidisciplinary approach, which should include cardiologists, a clinical geneticist, a genetic counselor, and the forensic pathologist directly involved in the sudden death case. This multifaceted cardiac genetic service is crucial in the evaluation and management of the clinical, genetic, psychological, and social complexities observed in families in which there has been a young sudden cardiac death. The present study will address the spectrum of structural substrates of cardiac sudden death with particular emphasis given to the possible role of forensic molecular biology techniques in identifying subtle or even merely functional disorders accounting for electrical instability.
Assuntos
Autopsia/normas , Morte Súbita Cardíaca/etiologia , Patologia Legal/normas , Autopsia/métodos , Bile/química , Análise Química do Sangue , Vasos Sanguíneos/patologia , Análise Mutacional de DNA , Morte Súbita Cardíaca/patologia , Saúde da Família , Toxicologia Forense/normas , Cabelo/química , Cardiopatias/diagnóstico , Valvas Cardíacas/patologia , Humanos , Imuno-Histoquímica , Anamnese , Microscopia Eletrônica , Miocárdio/patologia , Tamanho do Órgão , Guias de Prática Clínica como Assunto , RNA Mensageiro/metabolismo , Sarcoidose/diagnóstico , Coloração e Rotulagem , Urina/químicaRESUMO
The Authors, reviewing the Literature on asbestos-related Malignant Mesothelioma (MM), found that because of its very peculiar characteristics, the causal link between professional asbestos exposure and the development of this tumour is very difficult to define in respect to: diagnosis, causal link and individuation of possible culpable conducts. The evaluation of causal link in different medico-legal areas is studied by different criteria. In civil law the criterion of weak causality is followed to allow compensation for damages. For institutional purposes in INAIL, the definition of causal link is particularly facilitated by the legal presumption of origin. In fact it is sufficient, that asbestos-related lesions are ascertained in individuals who are or were exposed at any time of their professional life to the risk of inhaling asbestos fibres. In criminal law, the current approach of the Supreme Court is to demand evidence of strong causality, with a high logical probability and rational credibility, and beyond reasonable doubt, because criminal liability is personal as established in article 27 of the Italian Constitution. It is worth pointing out that all the levels of evidence indicated above must pass the test of scientific suitability or possibility.
Assuntos
Mesotelioma , Doenças Profissionais , Indenização aos Trabalhadores/legislação & jurisprudência , Humanos , Itália , Mesotelioma/diagnóstico , Mesotelioma/etiologia , Doenças Profissionais/diagnóstico , Doenças Profissionais/etiologiaRESUMO
Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiac entity characterized by right ventricular, or biventricular, fibrofatty replacement of myocardium. Structural alterations may lead to sudden cardiac death, mainly in young males during exercise. Autosomal dominant pattern of inheritance is reported in most parts of pathogenic genetic variations identified. Currently, 13 genes have been associated with the disease but nearly 40 % of clinically diagnosed cases remain without a genetic diagnosis. New genetic technologies allow further genetic analysis, generating a significant amount of genetic data in novel genes, which is often classified as of ambiguous significance. We focus on genetic advances of arrhythmogenic right ventricular cardiomyopathy, helping clinicians to interpret and translate genetic data into clinical practice.
Assuntos
Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Placofilinas/genética , Desmogleína 2 , Marcadores Genéticos/genética , Variação Genética/genética , HumanosRESUMO
PURPOSE: Ion channels are expressed both in the heart and in the brain, being advocated as responsible for sudden unexpected death in epilepsy but few pathogenic mutations have been identified. We aim to identify a novel gen associated with channelopathies and epilepsy in a family. METHODS: We assessed a family showing epilepsy concomitant with LQTS. Index case showed prolonged QT interval. His father suffers of LQT and epilepsy. We performed a direct sequencing analysis of KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A genes. RESULTS: We identified a non-synonymous heterozygous missense pathogenic mutation (p.L273F) in exon 6 of the KCNQ1 gene. All clinically affected relatives carried the same mutation. CONCLUSION: We report, for a first time, a KCNQ1 mutation in a family suffering of both phenotypes, suggesting that KCNQ1 genetic variations may confer susceptibility for recurrent seizure activity increasing the risk or lead to sudden death.
Assuntos
Epilepsia/complicações , Epilepsia/genética , Canal de Potássio KCNQ1/genética , Síndrome do QT Longo/complicações , Síndrome do QT Longo/genética , Mutação de Sentido Incorreto , Adulto , Epilepsia/fisiopatologia , Éxons , Família , Predisposição Genética para Doença , Heterozigoto , Humanos , Síndrome do QT Longo/fisiopatologia , Masculino , Linhagem , Adulto JovemRESUMO
The heritable cardiovascular disorder long QT syndrome (LQTS), characterized by prolongation of the QT interval on electrocardiogram, carries a high risk of sudden cardiac death. We sought to add new data to the existing knowledge of genetic mutations contributing to LQTS to both expand our understanding of its genetic basis and assess the value of genetic testing in clinical decision-making. Direct sequencing of the five major contributing genes, KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, was performed in a cohort of 115 non-related LQTS patients. Pathogenicity of the variants was analyzed using family segregation, allele frequency from public databases, conservation analysis, and Condel and Provean in silico predictors. Phenotype-genotype correlations were analyzed statistically. Sequencing identified 36 previously described and 18 novel mutations. In 51.3% of the index cases, mutations were found, mostly in KCNQ1, KCNH2, and SCN5A; 5.2% of cases had multiple mutations. Pathogenicity analysis revealed 39 mutations as likely pathogenic, 12 as VUS, and 3 as non-pathogenic. Clinical analysis revealed that 75.6% of patients with QTc≥500 ms were genetically confirmed. Our results support the use of genetic testing of KCNQ1, KCNH2, and SCN5A as part of the diagnosis of LQTS and to help identify relatives at risk of SCD. Further, the genetic tools appear more valuable as disease severity increases. However, the identification of genetic variations in the clinical investigation of single patients using bioinformatic tools can produce erroneous conclusions regarding pathogenicity. Therefore segregation studies are key to determining causality.
Assuntos
Testes Genéticos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/genética , Adolescente , Adulto , Biologia Computacional , Feminino , Genótipo , Humanos , Canais de Potássio KCNQ/genética , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , Canais de Sódio Disparados por Voltagem/genética , Adulto JovemRESUMO
BACKGROUND: The mechanism of sudden cardiac death in patients with heart failure (HF) is uncertain. Both electrical instability and structural remodelling could be factors that lead to fatal arrhythmias. We sought to analyse the expression of the sodium (SCN5A) and potassium (KCND3) channels as well as the fibrosis content in the ventricles of human HF and of non-diseased hearts under different post-mortem intervals. METHODS AND RESULTS: We analysed normal human hearts as controls [n=20 for the right ventricle (RV) and n=13 for the left ventricle (LV)] and human hearts from HF patients, which were obtained at the time of cardiac transplantation, as cases (n=48 for RV and n=34 for LV). Transcription of the SCN5A (probes SCN5A E4-5, E11-12, and E28) and KCND3 channels and of COLLAGEN I and III were assayed by real-time polymerase chain reaction. In addition, paraffin sections were used to analyse the percentage of collagen deposition in both cases and controls. KCND3 mRNA expression in the LV was lower in the cases than in controls (P<.001). Higher levels of SCN5A mRNA were found in the HF samples when analysed with probe SCN5A E4-5 (P<.05). SCN5A expression was lower in the controls with longer post-mortem interval (n=4) than in the controls with a shorter post- mortem interval (n=16, P<.01). KCND3 mRNA levels were also different between the two control groups (P<.05). Collagen deposition was higher in the LV tissues of the cases when compared to controls (P<.001), and it was higher in the LV from HF patients than in the RV (P<.05). Furthermore, collagen deposition was higher in the LV samples from patients with implanted cardiac defibrillator (ICD) therapy than in the LV of patients with no ICD therapy (P<.05). CONCLUSIONS: These data indicate that ionic and structural remodelling could be pathophysiological mechanisms of cardiac arrhythmias in HF patients.
Assuntos
Arritmias Cardíacas/metabolismo , Insuficiência Cardíaca/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Canais de Potássio Shal/metabolismo , Adulto , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/genética , Estudos de Casos e Controles , Colágeno/genética , Colágeno/metabolismo , Morte Súbita Cardíaca/etiologia , Desfibriladores Implantáveis , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/genética , Ventrículos do Coração/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Canal de Sódio Disparado por Voltagem NAV1.5/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Risco , Canais de Potássio Shal/genéticaRESUMO
We report on a young woman admitted to our Cardiology Unit because of an episode of cardiac arrest related to a long-QT syndrome (LQTS). This manifestation was part of a broader phenotype, which was recognized as a mild form of Beckwith-Wiedemann syndrome (BWS). Molecular analysis confirmed the diagnosis of BWS owing to a maternally inherited deletion of the centromeric imprinting center, or ICR2, an extremely rare genetic mechanism in BWS. The deletion interval (198 kb) also included exons 11-16 of the KCNQ1 gene, known to be responsible for LQTS at locus LQT1. No concomitant mutations were found in any other of the known LQT genes. The proposita's mother carries the same deletion in her paternal chromosome and shows manifestations of the Silver-Russell syndrome (SRS). This report describes the smallest BWS-causing ICR2 deletion and provides the first evidence that a paternal deletion of ICR2 leads to a SRS-like phenotype. In addition, our observation strongly suggests that in cases of LQTS due to mutation of the KCNQ1 gene (LQT1), an accurate clinical genetic evaluation should be done in order to program the most appropriate genetic tests.
Assuntos
Síndrome de Beckwith-Wiedemann/diagnóstico , Cromossomos Humanos Par 11/genética , Síndrome do QT Longo/diagnóstico , Deleção de Sequência , Síndrome de Beckwith-Wiedemann/genética , Hibridização Genômica Comparativa , Feminino , Impressão Genômica , Humanos , Síndrome do QT Longo/genética , Adulto JovemRESUMO
Cardiac arrhythmias are associated with abnormal channel function due to mutations in ion channel genes. Epilepsy is a disorder of neuronal function also involving abnormal channel function. It is increasingly demonstrated that the etiologies of long QT syndrome and epilepsy may partly overlap. However, only a few genetic studies have addressed a possible link between cardiac and neural channelopathies. We describe a family showing the association between Brugada syndrome and epilepsy in which a known mutation in the SCN5A gene (p.W1095X, c.3284G>A) was identified. We suggest that this mutation can be responsible for cardiac and brain involvement, probably at different developmental age in the same individual. This observation confirms the possibility that SCN5A mutations may confer susceptibility for recurrent seizure activity, supporting the emerging concept of a genetically determined cardiocerebral channelopathy.
Assuntos
Síndrome de Brugada/complicações , Síndrome de Brugada/genética , Epilepsia/complicações , Epilepsia/genética , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Adulto , Ondas Encefálicas/genética , Pré-Escolar , Análise Mutacional de DNA , Eletroencefalografia , Saúde da Família , Feminino , Humanos , MasculinoRESUMO
Placental Site Trophoblastic Tumor (PSTT) is a rare form of Gestational Trophoblastic Disease (GTD). Approximately 200 cases have been reported in the literature. This disease has unpredictable biological behavior, whereas approximately 10-15% have clinically malignant evolution. We present the case of a 21-year old woman at first pregnancy without known previous abortion at 25 weeks of amenorrhea who was admitted to the hospital for hyperemesis, hepatic problems and important weight loss registered during the last few months. Few days after the admission, the patient suddenly died before the doctors can reach a diagnosis. A forensic investigation for medical malpractice was initiated. Samples collected from uterus at the autopsy revealed large trophoblastic cells with eosinophilic cytoplasm. Deposition of fibrinoid material was noticed between trophoblastic cells. Tumor cells dissected through the myometrium and invaded into the vascular spaces. Specimens of the lungs revealed numerous small neoplastic emboli into the vessels. We show autopsy and histological findings of PSTT in a young woman, which are very rarely described in the literature and we discuss the medico-legal implications related to the great difficulties of the gynecologists who faced this rare condition in term of diagnosis and prediction of biological behavior, outlining effective therapeutic approaches.
Assuntos
Neoplasias Pulmonares/secundário , Complicações Neoplásicas na Gravidez/patologia , Tumor Trofoblástico de Localização Placentária/patologia , Neoplasias Uterinas/patologia , Evolução Fatal , Feminino , Humanos , Gravidez , Tumor Trofoblástico de Localização Placentária/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Each year, 1.2 million people die worldwide as a result of motor-vehicle accidents (MVA), representing a tremendous burden to healthcare. The aim of this study was to define the prevalence of coronary disease and its possible role in motor-vehicle accidents. METHODS AND RESULTS: We examined consecutive cases of non-hospital sudden death autopsies in the area of West Quebec during the period of 2002-2006, and we focused on those victims of MVA. Severe coronary artery disease (CAD) was defined as a narrowing of ≥ 75% of a cross-sectional area or the presence of acute plaque events in major epicardial coronary arteries. From a total cohort of 1260 autopsies, MVA were responsible for 123 deaths, 100 of whom were men and 23 were women. Significant CAD was documented in approximately 37% of these cases. In individuals older than 60 years, the prevalence of significant CAD and ischemia were 86.2% and 19.8%, respectively. A percentage of 40% of the coronary patients showed erratic driving before the accident, as observed by witnesses. Statistical analysis showed that an individual affected by CAD has 9% probability of suffering a motor-vehicle accident. CONCLUSIONS: The prevalence of severe CAD and acute myocardial ischemia is very high among individuals who have suffered a MVA. Our data suggest the hypothesis that acute CAD could be the cause of accidents in a large group of the drivers affected by coronary disease. For these reasons CAD could be investigated in drivers above 50 years old, as a possible preventive measure and determinant of individual risk stratification.
Assuntos
Doença da Artéria Coronariana/diagnóstico , Acidentes de Trânsito/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Aterosclerose/patologia , Autopsia , Teorema de Bayes , Doença da Artéria Coronariana/epidemiologia , Morte Súbita , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Placa Aterosclerótica/patologia , Prevalência , Probabilidade , Quebeque , RiscoRESUMO
The usefulness of post-mortem mRNA analysis and its potential applications in forensic casework is currently of interest, especially because of several factors affecting the quality of RNA samples that are not practically predictable. In fact, post-mortem RNA degradation is a complex process that has not been studied systematically. The purpose of this work is to establish whether RNA analysis from post-mortem heart tissue could be used as a forensic tool to investigate the cause of death, with special regard to those cases where a cardiac disease is suspected as the manner of death. We analysed heart tissue from 16 individuals with normal cardiac function, 9 with long post-mortem intervals (L-PMI) and 7 from organ donors with very short PMIs (S-PMIs). Right ventricle tissue was homogenised, and the RNA was isolated and reverse transcribed. The resulting cDNA was used in real-time PCR reactions to quantify the gene expression of beta-glucuronidase (GUSB), Nitric Oxide Synthase 3 (NOS3), Collagen 1 (COL1A1) and Collagen 3 (COL3A1). The percentage of samples with high-quality RNA was higher in samples with S-PMI (7 out of 7) than in samples with L-PMI (4 out of 9, p<0.05). No differences in PMI time or cause of exitus were found between samples with degraded or non-degraded RNA in the L-PMI group. When comparing mRNA levels in samples with non-degraded RNA, we found similar values between the L-PMI and S-PMI groups for GUSB, COL1A1 and COL3A1. The NOS3 gene expression in the L-PMI subgroup was less than half that in the S-PMI. These results suggest that high-quality mRNA can be extracted from post-mortem human hearts only in some cases. Moreover, our data show that mRNA levels are independent from the PMI, even though there are mRNAs in which the expression levels are very susceptible to ischemia times. Clear knowledge about the relationship between mRNA integrity and expression and PMI could allow the use of several mRNAs as forensic tools to contribute to the determination of the cause of death with special regard to cardiovascular diseases.