RESUMEN
PURPOSE: Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHADD) is a rare fatty acid oxidation disorder characterized by recurrent episodes of metabolic decompensation and rhabdomyolysis, as well as retinopathy, peripheral neuropathy, and cardiac involvement, such as infantile dilated cardiomyopathy. Because LCHADD patients are surviving longer, we sought to characterize LCHADD-associated major cardiac involvement in adolescence and young adulthood. METHODS: A retrospective cohort of 16 adolescent and young adult participants with LCHADD was reviewed for cardiac phenotype. RESULTS: Major cardiac involvement occurred in 9 of 16 participants, including sudden death, out-of-hospital cardiac arrest, acute cardiac decompensations with heart failure and/or in-hospital cardiac arrest, end-stage dilated cardiomyopathy, and moderate restrictive cardiomyopathy. Sudden cardiac arrest was more common in males and those with a history of infant cardiomyopathy. CONCLUSION: The cardiac manifestations of LCHADD in adolescence and early adulthood are complex and distinct from the phenotype seen in infancy. Life-threatening arrhythmia occurs at substantial rates in LCHADD, often in the absence of metabolic decompensation or rhabdomyolysis. The potential risk factors identified here-male sex and history of infant cardiomyopathy-may hint at strategies for risk stratification and possibly the prevention of these events.
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Errores Innatos del Metabolismo Lipídico , Fenotipo , Humanos , Masculino , Adolescente , Femenino , Adulto Joven , Adulto , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/patología , Estudios Retrospectivos , Rabdomiólisis/genética , Rabdomiólisis/patología , Rabdomiólisis/enzimología , 3-Hidroxiacil-CoA Deshidrogenasa de Cadena Larga/genética , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Cardiomiopatías/genética , Cardiomiopatías/patología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patologíaRESUMEN
AIMS: Mitral valve prolapse (MVP) is an accepted cause of sudden cardiac death (SCD) in most autopsy series. Diagnosis at autopsy relies upon subjective assessment with no established objective pathological criteria. This study set out to establish objective measurements to help pathologists dealing with SCD. METHODS: We diagnosed 120 (1.5%) cases of MVP in 8108 cases of SCD. We measured the mitral annulus, anterior and posterior leaflets, rough zone and mitral annular disjunction (MAD) in 27 MVP cases and compared them to 54 age- and sex-matched normal mitral valves. RESULTS: Age of death was 39 ± 16 years, with 59 females and 61 males. History of mild MV disease was present in 19 (16%). Eleven (9%) died associated with exertion. Left ventricular hypertrophy was present in nine (15%) females and 10 (16%) males. Both MV leaflets showed thickening and ballooning in all individuals. MVP showed highly significantly increased annular circumference, elongation and thickening of both leaflets as well as increased MAD (all P < 0.001). Left ventricular fibrosis was present in 108 (90%), with interstitial fibrosis in the posterolateral wall and papillary muscle in 88 (81%) and coexisting replacement fibrosis in 40 (37%). CONCLUSION: This is the largest MVP associated with SCD series highlighting a young cohort with equal representation of males and females. There is involvement of both leaflets with significant annular dilatation, elongation and thickening of both leaflets with MAD. Left ventricular fibrosis explains arrhythmia. Our quantitative measurements should serve as a reference for pathologists assessing post-mortem hearts for MVP.
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Prolapso de la Válvula Mitral , Válvula Mitral , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Válvula Mitral/patología , Prolapso de la Válvula Mitral/complicaciones , Prolapso de la Válvula Mitral/patología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Músculos Papilares/patología , FibrosisRESUMEN
High-risk coronary plaques (HRP) are characterized in clinical radiological imaging by the presence of low plaque attenuation, a napkin-ring sign (NRS), spotty calcifications (SC) and a positive remodeling index (RI). To evaluate if these signs are detectable in postmortem imaging by a multi-phase postmortem CT angiography (MPMCTA), a retrospective study of a series of autopsy well-documented coronary plaques related to sudden cardiac death (SCD) was performed. Then correlations between histological and radiological findings were described. Fourty SCD cases due to acute coronary syndrome based on clinical history and confirmed at autopsy were selected (28 men and 12 women, age 53.3 ± 10.9). The culprit lesion was mainly situated in the proximal segments of coronary arteries, in the right coronary artery in 23 cases (57.5%), the left anterior descending artery in 13 cases (32.5%), the circumflex artery in 3 cases (7.5%) and in one case in the left main stem. MPMCTA showed a positive RI (≥ 1.1) in 75% of cases with a mean RI 1.39 ± 0.71. RI values were lower in cases with fibrotic plaques. NRS was observed in 40% of cases, low attenuation plaque in 46.3%, and SC in 48.7% of cases. There were significant correlations of the radiological presence of NRS for fibrolipid composition of the plaque (p-value 0.007), severe intraplaque inflammation (p-value 0.017), severe adventitial inflammation (p-value 0.021) and an increased vasa vasorum (p-value 0.012). A significant correlation (p-value 0.002) was observed between the presence of SC at radiological examination and the presence of punctuate/fragmented calcification at histology. In addition, in 58.3% of cases, plaque enhancement was observed, which correlated with plaque inflammation and the fibrolipid composition of the plaque. The coronary artery calcium score was 314 (± 455). There was a poor agreement between stenosis of the lumen at histology versus radiology. Our study shows that the various radiological signs of HRP can be detected in all plaques by MPMCTA, but individually only to a variable extent; plaque enhancement appeared as a new sign of vulnerability. In the postmortem approach, these radiological markers of HRP, should always be applied in combination, which can be useful for developing a predictive model for diagnosing coronary SCD.
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Angiografía por Tomografía Computarizada , Muerte Súbita Cardíaca , Placa Aterosclerótica , Humanos , Femenino , Muerte Súbita Cardíaca/patología , Muerte Súbita Cardíaca/etiología , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Estudios Retrospectivos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Adulto , Anciano , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Angiografía Coronaria , Autopsia , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/patología , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/patología , Patologia Forense , Fibrosis , Imágenes Post MortemRESUMEN
Sudden cardiac death (SCD) is a major public health issue worldwide. In the young (< 40 years of age), genetic cardiomyopathies and viral myocarditis, sometimes in combination, are the most frequent, but underestimated, causes of SCD. Molecular autopsy is essential for prevention. Several studies have shown an association between genetic cardiomyopathies and viral myocarditis, which is probably underestimated due to insufficient post-mortem investigations. We report on four autopsy cases illustrating the pathogenesis of these combined pathologies. In two cases, a genetic hypertrophic cardiomyopathy was diagnosed in combination with Herpes Virus Type 6 (HHV6) and/or Parvovirus-B19 (PVB19) in the heart. In the third case, autopsy revealed a dilated cardiomyopathy and virological analyses revealed acute myocarditis caused by three viruses: PVB19, HHV6 and Epstein-Barr virus. Genetic analyses revealed a mutation in the gene coding for desmin. The fourth case illustrated a channelopathy and a PVB19/HHV6 coinfection. Our four cases illustrate the highly probable deleterious role of cardiotropic viruses in the occurrence of SCD in subjects with genetic cardiomyopathies. We discuss the pathogenetic link between viral myocarditis and genetic cardiomyopathy. Molecular autopsy is essential in prevention of these SCD, and a close collaboration between cardiologists, pathologists, microbiologists and geneticians is mandatory.
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Autopsia , Muerte Súbita Cardíaca , Herpesvirus Humano 6 , Miocarditis , Parvovirus B19 Humano , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/virología , Cardiomiopatía Dilatada/patología , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/patología , Causas de Muerte , Coinfección , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Muerte Súbita Cardíaca/prevención & control , Infecciones por Virus de Epstein-Barr/complicaciones , Resultado Fatal , Predisposición Genética a la Enfermedad , Herpesvirus Humano 4/genética , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/aislamiento & purificación , Mutación , Miocarditis/virología , Miocarditis/patología , Miocarditis/genética , Infecciones por Parvoviridae/complicaciones , Parvovirus B19 Humano/genética , Infecciones por Roseolovirus/complicaciones , Infecciones por Roseolovirus/virología , Infecciones por Roseolovirus/diagnóstico , Infecciones por Roseolovirus/patologíaRESUMEN
A 1-week-old girl died suddenly and unexpectedly. At autopsy the major finding was of a right dominant coronary artery circulation with an inapparent left coronary artery ostium. After careful examination, an anomalous origin of the left coronary artery was found with the ostium located in the non-coronary cusp immediately adjacent to the commissure of the non- and left coronary cusps. The ostium was of small caliber with an obliquely oriented artery (<45°) with no ostial ridges. The artery coursed anteriorly past the left coronary cusp between the aorta and the left atrial appendage to then follow its usual course inferiorly along the anterior aspect of the left ventricle. The reminder of the autopsy was unremarkable. Death was, therefore, attributed to an anomalous and hypoplastic left coronary artery (and ostium) with an acute angle of take-off. Tracing coronary arteries in the very young may be technically difficult due to their small size, thus identifying the location of ostia is important. This may be difficult when the ostium was located close to a commissure.
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Anomalías de los Vasos Coronarios , Humanos , Femenino , Anomalías de los Vasos Coronarios/patología , Anomalías de los Vasos Coronarios/diagnóstico , Recién Nacido , Autopsia , Vasos Coronarios/patología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Resultado Fatal , Muerte Súbita/etiología , Muerte Súbita/patologíaRESUMEN
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be clinically silent, and sudden unexpected death due to malignant arrhythmias may be the first manifestation. Thus, the HCM diagnosis could be performed at a clinical and judicial autopsy and offer useful findings on morphological features; moreover, it could integrate the knowledge on the genetic aspect of the disease. This review aims to systematically analyze the literature on the main post-mortem investigations and the related findings of HCM to reach a well-characterized and stringent diagnosis; the review was performed using PubMed and Scopus databases. The articles on the post-mortem evaluation of HCM by gross and microscopic evaluation, imaging, and genetic test were selected; a total of 36 studies were included. HCM was described with a wide range of gross findings, and there were cases without morphological alterations. Myocyte hypertrophy, disarray, fibrosis, and small vessel disease were the main histological findings. The post-mortem genetic tests allowed the diagnosis to be reached in cases without morpho-structural abnormalities; clinical and forensic pathologists have a pivotal role in HCM diagnosis; they contribute to a better definition of the disease and also provide data on the genotype-phenotype correlation, which is useful for clinical research.
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Cardiomiopatía Hipertrófica , Humanos , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/patología , Pruebas Genéticas , Arritmias Cardíacas/genética , Autopsia , Fibrosis , Fenotipo , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patologíaRESUMEN
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by the progressive fibro-fatty replacement of the right ventricular myocardium, leading to myocardial atrophy. Although the structural changes usually affect the right ventricle, the pathology may also manifest with either isolated left ventricular myocardium or biventricular involvement. As ARVC shows an autosomal dominant pattern of inheritance with variable penetrance, the clinical presentation of the disease is highly heterogeneous, with different degrees of severity and patterns of myocardial involvement even in patients of the same familiar group with the same gene mutation: the pathology spectrum ranges from the absence of symptoms to sudden cardiac death (SCD) sustained by ventricular arrhythmias, which may, in some cases, be the first manifestation of an otherwise silent pathology. An evidence-based systematic review of the literature was conducted to evaluate the state of the art of the diagnostic techniques for the correct post-mortem identification of ARVC. The research was performed using the electronic databases PubMed and Scopus. A methodological approach to reach a correct post-mortem diagnosis of ARVC was described, analyzing the main post-mortem peculiar macroscopic, microscopic and radiological alterations. In addition, the importance of performing post-mortem genetic tests has been underlined, which may lead to the correct identification and characterization of the disease, especially in those ARVC forms where anatomopathological investigation does not show evident morphostructural damage. Furthermore, the usefulness of genetic testing is not exclusively limited to the correct diagnosis of the pathology, but is essential for promoting targeted screening programs to the deceased's family members. Nowadays, the post-mortem diagnosis of ARVC performed by forensic pathologist remains very challenging: therefore, the identification of a clear methodological approach may lead to both a reduction in under-diagnoses and to the improvement of knowledge on the disease.
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Displasia Ventricular Derecha Arritmogénica , Autopsia , Humanos , Displasia Ventricular Derecha Arritmogénica/genética , Displasia Ventricular Derecha Arritmogénica/patología , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Muerte Súbita Cardíaca/patología , Muerte Súbita Cardíaca/etiología , Miocardio/patología , Ventrículos Cardíacos/patologíaRESUMEN
Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.
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Enfermedad de la Arteria Coronaria , Trombosis Coronaria , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/patología , Trombosis Coronaria/complicaciones , Trombosis Coronaria/patología , Factores de Riesgo , Enfermedad de la Arteria Coronaria/complicaciones , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patologíaRESUMEN
BACKGROUND: Anomalous coronary arteries are rare congenital variations with cases ranging from asymptomatic to life-threatening. Given the wide variability of coronary anomalies, it is challenging to predict their clinical consequences. Here, we present the 'malignant' variant - interarterial course of the left coronary artery between the aorta and pulmonary trunk - given the highest risk of sudden cardiac death among the various coronary anomalies. CASE PRESENTATION: Our case presents a 22-year-old male presenting to the emergency department after a syncopal episode that occurred while the patient was driving a motor vehicle. Initial Computed Tomography (CT) of the chest performed as part of the trauma work-up revealed a rare case of an anomalous origin of the left main coronary artery (LMCA) originating from a common ostium with the right coronary artery (RCA). The LMCA was found to have a malignant course, as it was positioned between the aorta and pulmonary artery. Given the high risk of sudden cardiac arrest with this congenital variant, the patient underwent coronary artery bypass grafting. CONCLUSION: Anomalous coronary arteries remain the second leading cause of sudden cardiac death in young adult patients. The risk of sudden cardiac death depends on the congenital variant of the anomalous coronary artery as well as the course these vessels take. This case highlights a rare congenital variant featuring both the LMCA and RCA originating from a common ostium, with the LMCA having a malignant course, a variant with the highest risk of sudden cardiac death.
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Anomalías de los Vasos Coronarios , Seno Aórtico , Masculino , Adulto Joven , Humanos , Adulto , Seno Aórtico/diagnóstico por imagen , Seno Aórtico/cirugía , Anomalías de los Vasos Coronarios/complicaciones , Anomalías de los Vasos Coronarios/diagnóstico por imagen , Anomalías de los Vasos Coronarios/cirugía , Puente de Arteria Coronaria/efectos adversos , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patologíaRESUMEN
OBJECTIVES: To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. METHODS: Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. RESULTS: The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. CONCLUSIONS: Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.
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Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Humanos , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patologíaRESUMEN
When exposed to oxidative and electrophilic stress, a protective antioxidant response is initiated by nuclear factor erythroid 2-related factor 2 (Nrf2). However, the extent of its importance in the forensic diagnosis of acute ischemic heart diseases (AIHD), such as myocardial infarction (MI), remains uncertain. On the other hand, immunohistochemical analyses of fibronectin (FN) and the terminal complement complex (C5b-9) prove valuable in identifying myocardial ischemia that precedes necrosis during the postmortem diagnosis of sudden cardiac death (SCD). In this study, we investigated the immunohistochemical levels of Nrf2, FN, and C5b-9 in human cardiac samples to explore their forensic relevance for the identification of acute cardiac ischemia. Heart samples were obtained from 25 AIHD cases and 39 non-AIHD cases as controls. Nrf2 was localized in the nuclei of cardiomyocytes, while FN and C5b-9 were detected in the myocardial cytoplasm. The number of intranuclear Nrf2 positive signals in cardiomyocytes increased in AIHD cases compared to control cases. Additionally, the grading of positive portions of cardiac FN and C5b-9 in the myocardium was also significantly enhanced in AIHD, compared to controls. Collectively, these results indicate that the immunohistochemical investigation of Nrf2 combined with FN, and/or C5b-9 holds the potential for identifying early-stage myocardial ischemic lesions in cases of SCD.
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Infarto del Miocardio , Isquemia Miocárdica , Factor 2 Relacionado con NF-E2 , Humanos , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Muerte Súbita Cardíaca/patología , Infarto del Miocardio/patología , Isquemia Miocárdica/metabolismo , Miocardio/metabolismo , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
INTRODUCTION AND OBJECTIVES: To investigate the epidemiological characteristics, clinic-pathological findings and recent use of substances of abuse and prescribed drugs in sexual activity-related sudden death (SArSD). METHODS: Multicenter population-based study on forensic autopsies conducted in 27 provinces of Spain over 12 years (2010-2021). RESULTS: Out of 18046 autopsied natural deaths, 64 cases (0.35 %) of SArSD were investigated (87 % males). Women were younger than males (50.5 ± 13.4 years vs 37.2 ± 14.2; p = 0.017). Sudden cardiac deaths (SCD) accounted for 87 % of cases. Ischemic heart disease was the predominant pathology (58 %), mainly affecting men ≥ 36 years of age. Cerebral haemorrhage (8 %) and asthma (5 %) were the leading non-cardiac causes. In young adults, SADS (36 %) and asthma (27 %) were the main causes The disease responsible of SCD was diagnosed in life in 7 subjects. In 64 % there were cardiovascular risk factors, mainly obesity. Toxicological analysis detected illicit drugs (23 %), mainly cocaine, medications for erectile dysfunction (9 %), and ethanol ≥ 0.5 g/L (8 %). Deaths occurred usually in the context of heterosexual intercourse and during or immediately after sexual activity. The most common location was at home (63 %). In 12 men the sexual partner was a sex worker. CONCLUSIONS: SArSD has a low incidence in the general population affecting middle-aged males during intercourse with a heterosexual partner. It is of cardiovascular origin, mainly due to ischemic heart disease that frequently remained silent during life. There is a frequent association with obesity, use of cocaine (and, to a lesser extent, medications for erectile dysfunction) and performing unconventional sexual practices. Forensic investigation is useful for developing prevention strategies.
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Asma , Cocaína , Disfunción Eréctil , Isquemia Miocárdica , Masculino , Persona de Mediana Edad , Adulto Joven , Humanos , Femenino , Disfunción Eréctil/complicaciones , Conducta Sexual , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Autopsia , Obesidad/complicaciones , Causas de MuerteRESUMEN
Approximately 1-2 per 100,000 young athletes die from sudden cardiac death (SCD) and extreme exercise may be associated with myocardial scar and arrhythmias. Racehorses have a high prevalence of atrial fibrillation (AF) and SCD but the presence of myocardial scar and inflammation has not been evaluated. Cardiac tissues from the left (LAA) and right (RAA) atrial appendages, left ventricular anterior (LVAPM) and posterior (LVPPM) papillary muscles, and right side of the interventricular septum (IVS-R) were harvested from racehorses with sudden cardiac death (SCD, n = 16) or other fatal injuries (OFI, n = 17), constituting the athletic group (ATH, n = 33), and compared to sedentary horses (SED, n = 10). Horses in the ATH group had myocyte hypertrophy at all sites; increased fibrosis at all sites other than the LAA; increased fibroblast infiltration but a reduction in the overall extracellular matrix (ECM) volume in the RAA, LVAPM, and IVS-R compared to SED horses. In this horse model, athletic conditioning was associated with myocyte hypertrophy and a reduction in ECM. There was an excess of fibrocyte infiltration and focal fibrosis that was not present in non-athletic horses, raising the possibility of an exercise-induced pro-fibrotic substrate.
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Condicionamiento Físico Animal , Remodelación Ventricular , Animales , Caballos , Muerte Súbita Cardíaca/patología , Muerte Súbita Cardíaca/veterinaria , Muerte Súbita Cardíaca/etiología , Enfermedades de los Caballos/patología , Fibrosis , Masculino , Miocardio/patología , Femenino , Matriz Extracelular , Miocitos Cardíacos/patologíaRESUMEN
The diagnosis of cardiomyopathy often relies on the subjective judgment of pathologists due to the variety of morphologic changes in the condition and its low specificity. This uncertainty can contribute to unexplained sudden cardiac deaths (USCD). To enhance the accuracy of hereditary cardiomyopathy diagnosis in forensic medicine, we proposed a combination of molecular autopsy and pathologic autopsy. By analyzing 16 deceased patients suspected of cardiomyopathy, using whole exome sequencing (WES) in molecular autopsy, and applying a combined diagnostic strategy, the study found pathogenic or likely pathogenic variants in 6 cases. Out of the 16 cases, cardiomyopathy was confirmed in 3, while 3 exhibited conditions consistent with it. Data for 4 cases was inconclusive, and cardiomyopathy was ruled out in 6. Notably, a novel variant of the TTN gene was identified. This research suggests that a grading diagnostic strategy, combining molecular and pathological evidence, can improve the accuracy of forensic cardiomyopathy diagnosis. This approach provides a practical model and strategy for precise forensic cause-of-death determination, addressing the limitations of relying solely on morphologic assessments in cardiomyopathy cases, and integrating genetic information for a more comprehensive diagnosis.
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Autopsia , Cardiomiopatías , Humanos , Cardiomiopatías/patología , Cardiomiopatías/genética , Cardiomiopatías/diagnóstico , Autopsia/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Patologia Forense/métodos , Secuenciación del Exoma , Conectina/genética , Muerte Súbita Cardíaca/patología , Anciano , Medicina Legal/métodos , Adulto Joven , Causas de MuerteRESUMEN
Sudden death by commotio cordis is rare. It is the consequence of a blunt trauma of the chest overlying the heart. The mechanism is a cardiac arrest by ventricular fibrillation in the absence of grossly or microscopically apparent myocardial injury. It has been reproduced in animals. The first historical case was reported by Giovanni Maria Lancisi in his book "De Subitaneis Mortibus'' published in 1707. Sudden death occurred in a man receiving a powerful blow under the xiphoid cartilage. Lancisi advanced the hypothesis of acute heart failure by a diastolic stand still ("death in diastole'').
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Commotio Cordis , Humanos , Commotio Cordis/historia , Commotio Cordis/etiología , Commotio Cordis/patología , Historia del Siglo XVIII , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Masculino , Paro Cardíaco/historia , Paro Cardíaco/etiología , Heridas no Penetrantes/historia , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/patología , Fibrilación Ventricular/historia , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/etiologíaRESUMEN
Left ventricular noncompaction (LVNC), involving mainly the right ventricle, is a rare form of congenital heart disorder characterized by a developmental arrest in myocardial compaction, resulting in a spongy appearance of the myocardium, mainly of the right ventricle, rarely detected in fetuses. We report the case of a female fetus with a gestational age of 41+4 weeks who came to our attention for intrapartum sudden unexpected death, resulting in stillbirth. The ventricular walls, particularly the right ventricular wall, appeared thick, hypertrabeculated and spongy, leading to the diagnosis of LVNC involving mainly the right ventricle. The atrioventricular node and His bundle presented areas of fetal dispersion and resorptive degeneration; islands of conduction tissue were detected in the central fibrous body. Arcuate nucleus of the brainstem showed bilateral severe hypoplasia. The right bundle branch was hypoplastic. The final cause of death was an electrical conduction disfunction in an LVNC involving mainly the right ventricle. To the best of our knowledge, the herein described case is the first reported observation of sudden intrapartum death from LVNC involving mainly the right ventricle well documented post-mortem with cardiac conduction and brainstem studies. Our findings confirm the need of an accurate post-mortem examination including the study of the cardiac conduction system on serial section in every case of sudden unexpected fetal death, although there are no universally recognized guidelines.
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Ventrículos Cardíacos , Mortinato , Humanos , Femenino , Embarazo , Ventrículos Cardíacos/anomalías , Ventrículos Cardíacos/patología , Adulto , Autopsia , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Edad Gestacional , No Compactación Aislada del Miocardio Ventricular/patología , No Compactación Aislada del Miocardio Ventricular/diagnóstico por imagen , Muerte FetalRESUMEN
The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive. This study assessed these relationships with cardiovascular imaging, electrocardiography, and the risks of sudden cardiac death (SCD), coronary events, and heart failure (HF) admission. We conducted a cross-sectional analysis of UK Biobank participants enrolled between 2006 and 2010. LTL was measured using quantitative polymerase chain reactions. Electronic health records were used to determine the incidence of SCD, coronary events, and HF admission. Cardiovascular measurements were made using cardiovascular magnetic resonance imaging and machine learning. The associations of LTL with SCD, coronary events, and HF admission and cardiac magnetic resonance imaging, electrocardiogram parameters of 33,043 and 19,554 participants were evaluated by multivariate regression. The median (interquartile range) follow-up period was 11.9 (11.2-12.6) years. Data was analyzed from January to May 2023. Among the 403,382 white participants without coronary artery disease or HF, 181,637 (45.0%) were male with a mean age of 57.1 years old. LTL was independently negatively associated with a risk of SCD (LTL third quartile vs first quartile: hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.72-0.92), coronary events (LTL third quartile vs first quartile: HR: 0.88, 95% CI: 0.84-0.92), and HF admission (LTL fourth quartile vs first quartile: HR: 0.84, 95% CI: 0.74-0.95). LTL was also independently positively associated with cardiac remodeling, specifically left ventricular mass index, left-ventricular-end systolic and diastolic volumes, mean left ventricular myocardial wall thickness, left ventricular stroke volume, and with electrocardiogram changes along the negative degree of T-axis. Cross-sectional study results showed that LTL was positively associated with heart size and cardiac function in middle age, but electrocardiography results did not show these associations, which could explain the negative association between LTL and risk of SCD, coronary events, and HF admission in UK Biobank participants.
Asunto(s)
Leucocitos , Fenotipo , Telómero , Humanos , Masculino , Femenino , Persona de Mediana Edad , Leucocitos/metabolismo , Estudios Transversales , Telómero/genética , Anciano , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/patología , Población Blanca/genética , Homeostasis del Telómero , Electrocardiografía , Factores de Riesgo , Reino Unido/epidemiología , Enfermedades Cardiovasculares/genéticaRESUMEN
A female neonate born with normal Apgar scores at 38+2 weeks of gestational age unexpectedly passed away within less than 30 hours after birth. The situation mirrored her brother's earlier demise within 24 hours post-delivery, suggesting a possible genetic disorder. Gross examination revealed widespread cyanosis and distinct yellowish changes on the cardiac ventricles. Histopathological examination disclosed lipid accumulation in the liver, heart, and kidneys. Tandem mass spectrometry detected elevated levels of 10 amino acids and 14 carnitines in cardiac blood. Trio-whole genome sequencing (Trio-WGS) identified the SLC25A20 c.199-10T>G mutation associated with carnitine-acylcarnitine translocase disease (CACTD), a type of fatty acid oxidation disorders (FAODs) with a potential for sudden death. Further validation of gene expression confirmed the functional deficiency of SLC25A20, ultimately diagnosing CACTD as the underlying cause of the neonate's demise. This case highlights the importance of prenatal metabolic and genetic screening for prospective parents and emphasizes the need for forensic doctors to integrate metabolomic and genomic investigations into autopsies for suspected inherited metabolic diseases.
Asunto(s)
Carnitina Aciltransferasas , Errores Innatos del Metabolismo Lipídico , Mutación , Humanos , Recién Nacido , Femenino , Carnitina Aciltransferasas/deficiencia , Carnitina Aciltransferasas/genética , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/patología , Errores Innatos del Metabolismo Lipídico/complicaciones , Errores Innatos del Metabolismo Lipídico/diagnóstico , Fenotipo , Resultado Fatal , Predisposición Genética a la Enfermedad , Muerte Súbita del Lactante/genética , Muerte Súbita del Lactante/patología , Muerte Súbita del Lactante/etiología , Autopsia , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Causas de Muerte , Carnitina/análogos & derivados , Carnitina/deficiencia , Proteínas de Transporte de Membrana Mitocondrial/genética , Miocardio/patología , Miocardio/metabolismo , Proteínas de Transporte de MembranaRESUMEN
The epidemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had a significant global impact, especially on immunosuppressed populations such as heart transplant recipients. While SARS-CoV-2 initially infects the respiratory system, cardiovascular complications induced by coronavirus disease 2019 (COVID-19) include cardiac arrest, myocardial infarction, heart failure, myocarditis, arrhythmia, acute myocyte injury, thrombotic events, and cardiogenic shock. Here, we present a case of a 45-year-old African American male who tested positive for COVID-19 infection six months after receiving a heart transplant. The patient was asymptomatic initially, but two weeks later he developed dyspnea, early satiety, and abdominal bloating. The patient was admitted to the hospital for acute renal failure and subsequently diagnosed with moderate acute T cell-mediated allograft rejection (Grade 2R) by endomyocardial biopsy. Three months after testing positive for COVID-19, the patient suffered a sudden cardiac death. At autopsy, the epicardium was diffusely edematous and showed vascular congestion. The coronary arteries showed a striking concentric narrowing of lumens and diffusely thickened arterial walls of all major extramural arteries deemed consistent with a rapidly progressive form of cardiac allograft vasculopathy (CAV). SARS-CoV-2 nucleocapsid protein was localized by immunohistochemistry (IHC) in endothelial cells of venules and capillaries within the epicardium. Our localization of SARS-CoV-2 in coronary vessel endothelial cells by IHC suggests that endothelial cell infection, endotheliitis, and immune-related inflammation may be a primary mechanism of vascular injury. The present case represents an early onset rapidly progressive form of CAV. This case may be the first case of post-transplant arteriopathy occurring in such a short time that includes corresponding autopsy, surgical pathology, and IHC data.
Asunto(s)
COVID-19 , Trasplante de Corazón , Humanos , COVID-19/complicaciones , Trasplante de Corazón/efectos adversos , Masculino , Persona de Mediana Edad , Resultado Fatal , Rechazo de Injerto/patología , Rechazo de Injerto/inmunología , SARS-CoV-2/patogenicidad , Progresión de la Enfermedad , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/etiologíaRESUMEN
This study aimed to assess the frequency and association between transthyretin-derived (ATTR) amyloidosis and sarcoidosis in a large autopsy cohort including many cases of sudden cardiac death (SCD). We identified 73 sporadic ATTR amyloidosis cases and 11 sarcoidosis cases, among which we found two cases with concomitant ATTR amyloidosis and sarcoidosis (2.4% of all cases; 2.7% within the sporadic ATTR group). The first case involved a 92-year-old man who experienced SCD. In this patient's heart, we observed ATTR deposition and noncaseating epithelioid granulomas consistent with sarcoidosis. Focally, ATTR deposits and granulomas co-localized, with histiocyte phagocytosis of transthyretin-immunoreactive fragments. However, in most lesions, they were distributed independently. The second case was that of an 86-year-old woman who also experienced SCD. In this patient, we detected ATTR deposition in the heart and lung, while noncaseating epithelioid granulomas were only observed in the lung, liver, kidney, and thyroid. Furthermore, no co-localization of the two lesions was observed. Based on these findings, we concluded that the coexistence of ATTR amyloidosis and sarcoidosis was likely coincidental. Nevertheless, despite the rarity of the combination of these two diseases, it should be recognized as a potential cause of SCD, especially among elderly people.