Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.103
Filtrar
1.
Virchows Arch ; 476(2): 179-194, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31522288

RESUMO

Ischemic heart disease is one of the leading causes of morbidity and death worldwide. Consequently, myocardial infarctions are often encountered in clinical and forensic autopsies, and diagnosis can be challenging, especially in the absence of an acute coronary occlusion. Precise histopathological identification and timing of myocardial infarction in humans often remains uncertain while it can be of crucial importance, especially in a forensic setting when third person involvement or medical responsibilities are in question. A proper post-mortem diagnosis requires not only up-to-date knowledge of the ischemic coronary and myocardial pathology, but also a correct interpretation of such findings in relation to the clinical scenario of the deceased. For these reasons, it is important for pathologists to be familiar with the different clinically defined types of myocardial infarction and to discriminate myocardial infarction from other forms of myocardial injury. This article reviews present knowledge and post-mortem diagnostic methods, including post-mortem imaging, to reveal the different types of myocardial injury and the clinical-pathological correlations with currently defined types of myocardial infarction.


Assuntos
Autopsia , Infarto do Miocárdio/diagnóstico , Miocárdio/patologia , Autopsia/métodos , Morte Súbita Cardíaca/patologia , Patologia Legal/métodos , Humanos , Infarto do Miocárdio/patologia , Patologia Clínica/métodos
2.
Cardiovasc Pathol ; 44: 107157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31760239

RESUMO

An apparently healthy man died suddenly at the age of 49 during physical activity. The heart was referred to our Cardiovascular Pathology Unit for valve tissue banking. Pathology findings led to the diagnosis of arrhythmogenic left ventricular cardiomyopathy. Molecular autopsy was performed and two variants of interest were identified in genes associated with arrhythmogenic cardiomyopathy. The 19-year-old son underwent a cardiac screening comprehensive of electrocardiogram (ECG), echocardiogram, cardiac magnetic resonance and genetic testing, and the diagnosis of arrhythmogenic left ventricular cardiomyopathy was achieved. This case report highlights the need of a systematic evaluation of all sudden death victims with autopsy performed by expert cardiovascular pathologists and implemented by molecular analysis, aiming to identify also rare hereditary diseases and activate proper family screening.


Assuntos
Displasia Arritmogênica Ventricular Direita/genética , Morte Súbita Cardíaca/etiologia , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/patologia , Autopsia , Causas de Morte , Morte Súbita Cardíaca/patologia , Evolução Fatal , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Patologia Molecular
3.
Cardiovasc Pathol ; 44: 107154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31760242

RESUMO

Although the cause of eosinophilic coronary periarteritis (ECPA) remains unclear, an allergic background is present in fewer patients than expected. A 50-year-old man with no history of allergy or symptoms suggestive of cardiac or respiratory disorders suddenly died shortly after oral administration of loxoprofen sodium. Autopsy showed eosinophilic coronary periarteritis in three main branches of the coronary arteries, characterized by eosinophil-predominant inflammation without fibrinoid necrosis or granulomatous change in the adventitia and its surroundings of the three main branches of the coronary arteries, in addition to the localized sign of bronchial asthma in the lung. Immunohistochemical examination showed that many mast cells positive for human mast cell tryptase were evident in the perivascular tissue containing peripheral nerve trunks. Whereas the blood concentration of loxoprofen sodium was within the therapeutic range, significant elevation of the serum histamine and tryptase levels was found. The present case suggests that eosinophilic coronary periarteritis may be caused by a type I allergic reaction in some patients and that loxoprofen sodium can trigger a life-threatening type I allergic reaction, including eosinophilic coronary periarteritis, leading to sudden unexpected death.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doença da Artéria Coronariana/induzido quimicamente , Vasos Coronários/efeitos dos fármacos , Morte Súbita Cardíaca/etiologia , Hipersensibilidade a Drogas/etiologia , Eosinofilia/induzido quimicamente , Fenilpropionatos/efeitos adversos , Dor de Ombro/tratamento farmacológico , Autopsia , Causas de Morte , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/imunologia , Vasos Coronários/patologia , Morte Súbita Cardíaca/patologia , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/patologia , Eosinofilia/imunologia , Eosinofilia/patologia , Evolução Fatal , Humanos , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , Pessoa de Meia-Idade
4.
Sensors (Basel) ; 20(1)2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31861320

RESUMO

Heart diseases are among the most common death causes in the population. Particularly, sudden cardiac death (SCD) is the cause of 10% of the deaths around the world. For this reason, it is necessary to develop new methodologies that can predict this event in the earliest possible stage. This work presents a novel methodology to predict when a person can develop an SCD episode before it occurs. It is based on the adroit combination of the empirical mode decomposition, nonlinear measurements, such as the Higuchi fractal and permutation entropy, and a neural network. The obtained results show that the proposed methodology is capable of detecting an SCD episode 25 min before it appears with a 94% accuracy. The main benefits of the proposal are: (1) an improved detection time of 25% compared with previously published works, (2) moderate computational complexity since only two features are used, and (3) it uses the raw ECG without any preprocessing stage, unlike recent previous works.


Assuntos
Morte Súbita Cardíaca/patologia , Eletrocardiografia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Entropia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Adulto Jovem
5.
West Afr J Med ; 36(3): 286-289, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622494

RESUMO

Sarcoidosis is a chronic granulomatous disease with multi-systemic involvement and with varied forms of presentation. The diagnosis can often be a challenge particularly due to the non-specific nature of the disease. It is often silent and may require no active treatment except during flares. We present the case of a middle age lady with pulmonary sarcoidosis who had sudden death from cardiac affectation without prior cardiac symptoms. We concluded that active cardiac assessment is a prudent step in patients presenting with sarcoidosis regardless of the organ of affectation at presentation or diagnosis.


Assuntos
Morte Súbita Cardíaca/etiologia , Sarcoidose Pulmonar/complicações , Cardiomiopatias , Morte Súbita Cardíaca/patologia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Sarcoidose Pulmonar/patologia
6.
Rev Port Cardiol ; 38(7): 503-509, 2019 07.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31522937

RESUMO

In up to one-third of cases of sudden death, the medico-legal autopsy finding is inconclusive, and the option to perform a molecular autopsy is covered in international guidelines. The importance of postmortem genetic testing lies in its ability to identify hereditary diseases, often those with an autosomal dominant transmission pattern, and, through consultations and screening of relatives, to identify family members with a pathogenic mutation, who are often asymptomatic, providing an opportunity to change the course of their lives. The authors present three clinical cases that highlight the importance of postmortem genetic studies and family studies, as well as the integration of the data obtained in a cardiology consultation, which may be for arrhythmology, coronary disease or cardiomyopathy, depending on the specific condition. This could modify the course of the disease in many relatives.


Assuntos
Síndrome de Brugada/diagnóstico , Morte Súbita Cardíaca/patologia , Testes Genéticos/métodos , Adolescente , Adulto , Autopsia , Síndrome de Brugada/complicações , Síndrome de Brugada/genética , Morte Súbita Cardíaca/etiologia , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Cardiovasc Pathol ; 42: 54-58, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31306942

RESUMO

Kawasaki disease (KD) is among one of the most common causes of vasculitis in children. Since KD was first described in 1967, there have been several reports of patients who did not meet the full diagnostic criteria for KD but who ultimately developed significant coronary artery lesions. Children with incomplete KD are at similar risk of developing coronary artery abnormalities to those with complete Kawasaki. A previously healthy 13-year-old Asian male was seen at a clinic for fever, pharyngitis, and conjunctivitis. He was given antibiotics for a presumed streptococcal pharyngitis. Two weeks later, the decedent complained of chest pain, collapsed, and was transported by Emergency Medical Services to a nearby hospital where he was pronounced deceased on arrival. A complete autopsy was done by the local medical examiner. Histologically, all three coronary arteries showed varying degrees of severe transmural lymphoplasmacytic inflammation, marked vascular smooth muscle intimal proliferation, focal destruction of muscular and elastic layers, and luminal stenosis. Some vessels had recent thrombi. We present an example of incomplete KD in an older child and reiterate the importance of obtaining relevant medical history in sudden death cases that come to the Medical Examiner Office, especially in the pediatric age group.


Assuntos
Trombose Coronária/etiologia , Vasos Coronários/patologia , Morte Súbita Cardíaca/etiologia , Síndrome de Linfonodos Mucocutâneos/complicações , Adolescente , Causas de Morte , Trombose Coronária/patologia , Morte Súbita Cardíaca/patologia , Evolução Fatal , Humanos , Masculino , Síndrome de Linfonodos Mucocutâneos/patologia
10.
Int J Mol Sci ; 20(10)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31096574

RESUMO

Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder characterized by the progressive substitution of functional myocardium with noncontractile fibro-fatty tissue contributing to ventricular arrhythmias and sudden cardiac death. Cyclophilin A (CyPA) is a ubiquitous protein involved in several pathological mechanisms, which also characterize ACM (i.e., fibrosis, inflammation, and adipogenesis). Nevertheless, the involvement of CyPA in ACM cardiac remodeling has not been investigated yet. Thus, we first evaluated CyPA expression levels in the right ventricle (RV) tissue specimens obtained from ACM patients and healthy controls (HC) by immunohistochemistry. Then, we took advantage of ACM- and HC-derived cardiac mesenchymal stromal cells (C-MSC) to assess CyPA modulation during adipogenic differentiation. Interestingly, CyPA was more expressed in the RV sections obtained from ACM vs. HC subjects and positively correlated with the adipose replacement extent. Moreover, CyPA was upregulated at early stages of C-MSC adipogenic differentiation and was secreted at higher level over time in ACM- derived C-MSC. Our study provides novel ex vivo and in vitro information on CyPA expression in ACM remodeling paving the way for future C-MSC-based mechanistic and therapeutic investigations.


Assuntos
Arritmias Cardíacas/metabolismo , Cardiomiopatias/metabolismo , Ciclofilina A/metabolismo , Remodelação Ventricular , Adipogenia/fisiologia , Tecido Adiposo/patologia , Arritmias Cardíacas/patologia , Cardiomiopatias/patologia , Diferenciação Celular , Ciclofilina A/genética , Morte Súbita Cardíaca/patologia , Fibrose , Expressão Gênica , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Inflamação , Células-Tronco Mesenquimais/patologia , Miocárdio
11.
Avian Pathol ; 48(5): 444-453, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31081346

RESUMO

Sudden death syndrome (SDS) is a stress-related disease in broilers with no diagnostic clinical or necropsy findings. SDS is associated with ventricular tachycardia (VT) and ventricular fibrillation (VF); however, its pathogenesis is not precisely described at the molecular level. Dysfunction of ryanodine receptor 2 (RYR2), that controls rapid release of Ca2+ from the sarcoplasmic reticulum (SR) into the cytosol during muscle contraction, has been associated with VT and sudden cardiac death (SCD) in human patients with structurally normal heart, but there is no report describing abnormalities in RYR2 in diseased broilers. In order to advance our knowledge on the molecular mechanisms predisposing broilers to fatal arrhythmia, the present study was conducted to determine the occurrence of possible mutations and changes in the expression level of the chicken RYR2 gene (chRYR2) in broilers that died from SDS. An increase in mRNA expression level and nine novel point mutations in chRYR2 were found in relation to SDS. In conclusion, susceptibility to lethal cardiac arrhythmia in SDS may be associated with specific changes in intracellular Ca2+ cycling components such as RYR2 due to mutation and dysregulation. Finding the probable association of SDS with gene defects can be applied to select for chickens with lower susceptibility to SDS and decrease the poultry industry losses due to SDS mortality. RESEARCH HIGHLIGHTS Investigation of the occurrence of possible mutations and changes in the expression level of chicken RYR2 gene (chRYR2) in broilers that died from SDS. Increase in the mRNA expression level of chRYR2 in relation to SDS. Nine novel point mutations in chRYR2 of broilers that died from SDS. Possible connection between susceptibility to lethal cardiac arrhythmia in SDS and changes in intracellular Ca2+ cycling machinery, such as RYR2, due to mutation and dysregulation.


Assuntos
Cálcio/metabolismo , Morte Súbita Cardíaca/veterinária , Doenças das Aves Domésticas/patologia , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Sequência de Aminoácidos , Animais , Galinhas , Morte Súbita Cardíaca/patologia , Feminino , Masculino , Modelos Moleculares , Miocárdio/patologia , Mutação Puntual , RNA Mensageiro/genética , Alinhamento de Sequência/veterinária , Taquicardia Ventricular/patologia
12.
Eur. j. anat ; 23(3): 159-165, mayo 2019. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-182977

RESUMO

The coronary ostia (CO) lie within the left and right aortic sinuses, respectively; and are bound by the sinotubular junction (STJ) superiorly. The high frequency of cardiac procedures that require catheterization has necessitated the reappraisal of the anatomy of the origin of the coronary arteries. Therefore, this study aimed to describe the CO by recording its diameter, shape, and relation to the sinotubular junction in a select South African population.The present study included the gross dissection of 50 formalin fixed, adult cadaveric hearts. The average diameter of the right coronary ostium (RCO) was 3.29mm and the left coronary ostium (LCO) was 3.87mm. With regard to the shape of the ostia, the RCO was described as circular in 52% (26/50), horizontally ellipsoid in 24% (12/50) and vertically ellipsoid in 24% (12/50) of cases. The LCO was circular in 30% (15/50), horizontally ellipsoid in 60% (30/50) and vertically ellipsoid in 10% (5/50) of cases. The RCO was located below the STJ in 88% (44/50) and at the level of the STJ in 12% (6/50) of cases. The LCO was recorded below the STJ in 64% (32/50), at the level of the STJ in 32% (16/50) and above the STJ in 4% (2/50) of cases. Multiple ostia arising from a single aortic sinus was recorded in 14% (7/50) of cases. In 2% (1/50) of cases, the RCO was located in the non-coronary sinus. In addition, the RCO arose from the left aortic sinus in 2% of cases. The results of the present study correlate with those of previous studies. Anomalous CO, although asymptomatic has been linked to myocardial infarction and sudden cardiac death. It is, therefore, imperative for the clinician to be aware of variant CO anatomy, which may alert them to the predisposition of cardiac risks


No disponible


Assuntos
Humanos , Infarto do Miocárdio/mortalidade , Cadáver , Seio Coronário/anatomia & histologia , Aorta/anatomia & histologia , Coração/anatomia & histologia , Morte Súbita Cardíaca/patologia , África Austral/etnologia , Vasos Coronários/anatomia & histologia
13.
Malays J Pathol ; 41(1): 51-54, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31025638

RESUMO

Spontaneous coronary artery dissection is a rare event and commonly associated with pregnancy and female gender. This condition can reduce or completely obstruct the blood flow to the heart, causing a myocardial ischaemia, abnormalities in heart rhythm or sudden death. We present a case of a 28-year-old Indian male with no previous medical illness who complained sudden onset of chest pain prior to his death. Autopsy revealed a left anterior descending coronary artery dissection associated with plaque rupture. The anterior wall of left ventricle showed contraction band necrosis. There was also atheroma present in the right coronary artery which was insignificant. Histologically, dissection was associated with atherosclerosis. There was no evidence of vasculitis. The cause of death was given as coronary artery dissection due to coronary artery atherosclerosis.


Assuntos
Doença da Artéria Coronariana/complicações , Anomalias dos Vasos Coronários/etiologia , Morte Súbita Cardíaca/etiologia , Doenças Vasculares/congênito , Adulto , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/patologia , Anomalias dos Vasos Coronários/mortalidade , Anomalias dos Vasos Coronários/patologia , Morte Súbita Cardíaca/patologia , Humanos , Masculino , Doenças Vasculares/etiologia , Doenças Vasculares/mortalidade , Doenças Vasculares/patologia
14.
Leg Med (Tokyo) ; 38: 73-76, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31030120

RESUMO

Commotio Cordis (CC) diagnosis is based on the occurrence of a blunt, non-penetrating blow to the chest preceding cardiovascular collapse and the absence of structural damage that would explain any observed effects. In CC lethal cases, the execution of the autopsy represents a possible diagnostic tool. Nevertheless, to date in the literature no author expresses an opinion about the use of the autopsy. In the light of the above, the authors propose a review of the literature about this topic. The review consents to state that the occurrence of a blunt blow to the chest is a necessary element for a lethal CC diagnosis, but it cannot be considered enough. Indeed, because CC is a recognized cause of sudden cardiac death, the autopsy should be always performed to exclude the presence of structural damage that would explain any observed effects. This approach is fundamental in order to achieve an accurate diagnosis and to distinguish CC from other causes of sudden cardiac death. In addition, the authors sustain that in case of autopsy data's lack the authors should not identify CC diagnosis as definitive but as possible.


Assuntos
Autopsia , Commotio Cordis/diagnóstico , Commotio Cordis/patologia , Patologia Legal , Commotio Cordis/etiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/patologia , Diagnóstico Diferencial , Humanos , Contusões Miocárdicas/complicações , Contusões Miocárdicas/patologia
15.
Leg Med (Tokyo) ; 38: 1-4, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30861484

RESUMO

Acute myocarditis is related to a significant number of sudden deaths among young adults and its diagnosis is often demanded to post-mortem investigations performed on a forensic setting. Eosinophilic myocarditis (EM) is a rare form of myocarditis that is pathologically characterized by myocardial inflammation with eosinophils, often in association with elevated levels of circulating blood eosinophils. The sudden death of a 19-year-old boy with no past medical history is reported. Diagnosis of fatal acute EM was performed after a comprehensive investigation including an in-depth analysis of anamnestic and circumstantial data, and complete autopsy followed by toxicologic and cardio-pathological investigations. Discussion focuses on the forensic issues related to diagnosis and therapy of this rare form of acute myocarditis. As acute EM may be patchy, extensive myocardial sampling is mandatory in order to recognize the extent and the phase of the disease. An early diagnosis is the basis for a timely therapy, which is the key-point for prevent extensive myocardial damage, allowing a better outcome, especially when EM is acute and necrotizing. However, as demonstrated from the case herein reported, the course of EM is sometimes fulminant and does not allow any therapy nor even clinical diagnosis. Finally, this paper serves as reminder to consider this infrequent disease in differential diagnosis when facing with a sudden death, even in a young subject and in the absence of any prodrome.


Assuntos
Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/patologia , Eosinofilia/complicações , Eosinofilia/patologia , Patologia Legal , Miocardite/complicações , Miocardite/patologia , Miocárdio/patologia , Doença Aguda , Adulto , Autopsia , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Humanos , Masculino , Miocardite/diagnóstico , Necrose , Adulto Jovem
16.
Vet Pathol ; 56(4): 576-585, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30917748

RESUMO

Postmortem evaluation of racehorses has focused primarily on musculoskeletal injuries; however, horses also die suddenly on the track (sudden death [SD]). Although cardiac conditions are frequently suspected as a cause of death, SD racehorses are often autopsy negative; however, previous studies have been limited due to inconsistent or insufficient cardiac sampling and lack of controls. SD in New York (NY) and Maryland (MD) racehorses was evaluated in an observational case vs control study comparing clinical information, postmortem evaluation including cardiac dissection, and cardiac conduction system histopathology. In the study period, there were 40 cases of SD. In NY, SD occurred in 12% (37/316) of submissions, and 36 (11%) cases of SD were exercise associated (EASD); 3 EASD cases occurred in MD. In NY/MD EASD cases with histologic examination of the heart, 11 of 36 (31%) had significant lesions, including mesenteric artery rupture (1), axial trauma (2), systemic inflammation (2), pulmonary hemorrhage (1), and cardiac disease (5). Mild myocardial fibrosis, mild inflammation, coronary arteriosclerosis, and variation in cardiac nodal connective tissue were present in both SD cases and controls and thus were not considered to be causes of SD. While not excluding a genetic basis for SD, analysis of the genotypes (GGP Equine 70 K Array) of cases and controls did not reveal significant differences in allele frequencies at any locus. Most SD racehorses were autopsy negative; further research using standardized protocols and controls is needed to understand the underlying causes of SD, which is crucial to protecting the viability of racing.


Assuntos
Doença da Artéria Coronariana/veterinária , Morte Súbita Cardíaca/veterinária , Hemorragia/veterinária , Doenças dos Cavalos/patologia , Pneumopatias/veterinária , Animais , Autopsia/veterinária , Doença da Artéria Coronariana/patologia , Morte Súbita Cardíaca/patologia , Feminino , Genômica , Hemorragia/patologia , Doenças dos Cavalos/diagnóstico , Cavalos , Pneumopatias/patologia , Masculino , Maryland , Miocárdio/patologia , New York , Condicionamento Físico Animal , Estudos Retrospectivos
17.
Hum Mol Genet ; 28(11): 1919-1929, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715372

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function.


Assuntos
Arritmias Cardíacas/genética , Cardiomiopatia Hipertrófica/mortalidade , Insuficiência Cardíaca/genética , Proteínas Repressoras/genética , Adulto , Animais , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Morte Súbita Cardíaca/patologia , Desmina/genética , Modelos Animais de Doenças , Feminino , Ligação Genética/genética , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Homozigoto , Humanos , Masculino , Mutação , Linhagem , Fenótipo , Peixe-Zebra/genética
18.
Circulation ; 139(15): 1786-1797, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30700137

RESUMO

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. METHODS: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents. CONCLUSIONS: SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM before death.


Assuntos
Displasia Arritmogênica Ventricular Direita/mortalidade , Morte Súbita Cardíaca/etiologia , Ventrículos do Coração/patologia , Disfunção Ventricular Esquerda/mortalidade , Adulto , Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/patologia , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Causas de Morte , Morte Súbita Cardíaca/patologia , Feminino , Predisposição Genética para Doença , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Adulto Jovem
19.
Hong Kong Med J ; 25(1): 21-9, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30670673

RESUMO

OBJECTIVE: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. METHODS: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing. RESULTS: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. CONCLUSION: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists.


Assuntos
Arritmias Cardíacas/genética , Morte Súbita Cardíaca/etiologia , Sequenciamento de Nucleotídeos em Larga Escala , Anamnese/estatística & dados numéricos , Mutação , Adolescente , Adulto , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Autopsia , Causas de Morte , Criança , Morte Súbita Cardíaca/patologia , Feminino , Predisposição Genética para Doença , Testes Genéticos , Hong Kong , Humanos , Masculino , Fenótipo , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
20.
Curr Cardiol Rev ; 15(1): 30-37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30210005

RESUMO

BACKGROUND: Sudden death of a newborn is a rare entity, which may be caused by genetic cardiac arrhythmias. Among these diseases, Long QT syndrome is the most prevalent arrhythmia in neonates, but other diseases such as Brugada syndrome, Short QT syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia also cause sudden death in infants. All these entities are characterized by well-known alterations in the electrocardiogram and the first symptom of the disease may be an unexpected death. Despite the low prevalence of these diseases, the performance of an electrocardiogram in the first hours or days after birth could help identify these electrical disruptions and adopt preventive measures. In recent years, there has been an important impulse by some experts in the scientific community towards the initiation of a newborn electrocardiogram-screening program, for the detection of these electrocardiographic abnormalities. In addition, the use of genetic analysis in neonates could identify the cause of these heart alterations. Identification of relatives carrying the genetic alteration associated with the disease allows adoption of measures to prevent lethal episodes. CONCLUSION: Recent technological advances enable a comprehensive genetic screening of a large number of genes in a cost-effective way. However, the interpretation of genetic data and its translation into clinical practice are the main challenges for cardiologists and geneticists. However, there is important controversy as to the clinical value, and cost-effectiveness of the use of electrocardiogram as well as of genetic testing to detect these cases. Our review focuses on these current matters of argue.


Assuntos
Morte Súbita Cardíaca/patologia , Eletrocardiografia/métodos , Testes Genéticos/métodos , Síndrome do QT Longo/diagnóstico , Humanos , Lactente , Recém-Nascido , Síndrome do QT Longo/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA