Sudden Death Victims Research Articles

Whole genome and transcriptome sequencing of post-mortem cardiac tissues from sudden cardiac death victims identifies a gene regulatory variant in NEXN.

Sudden cardiac death (SCD) is a major public health problem and constitutes a diagnostic and preventive challenge in forensic pathology, especially for cases with structural normal hearts at autopsy, so-called sudden arrhythmic death syndrome (SADS). The identification of new genetic risk factors that predispose to SADS is important, because they may contribute to establish the diagnosis and increase the understanding of disease pathways underlying SADS. Pathogenic mutations in the protein coding regions of cardiac genes were found in relation to SADS. However, much remains unknown about variants in non-coding regions of the genome. In this study, we explored the potential of whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) to find DNA variants in SCD victims with structural normal hearts. With focus on the non-coding regulatory regions, we re-examined a cohort of 13 SADS and sudden unexplained death in infancy (SUDI) victims without disease causing DNA variants in recognized cardiac genes. The genetic re-examination of DNA was carried out using frozen tissue samples and WTS was carried out using five distinct formalin fixed and paraffin embedded (FFPE) cardiac tissue samples from each individual, including anterior and posterior walls of the left ventricle, ventricular papillary muscle, septum, and the right ventricle. We identified 23 candidate variants in regulatory sequences of cardiac genes, including a variant in the promotor region of NEXN, c.-194A>G, that was found to be statistically significantly (p < 0.05) associated with decreased expression of NEXN and cardiac hypertrophy. With the use of post-mortem FFPE tissues, we highlight the potential of using WTS investigations and compare gene expression levels with DNA variation in regulatory non-coding regions of the genome for a better understanding of the genetics of cardiac diseases leading to SCD.

The Analysis of the Causes of Sudden Deaths Among Workers of Locomotive Crews

to analyze causes of sudden death (SD) of workers of locomotive crews.Materials and methods.We performed the retrospective analysis of SDs of employees of Joint Stock Company ( JSC) "Russian Railways" for the period 2009-2017 (total 119 cases).Results.As a rule, the combination of risk factors of development of cardiovascular diseases was present, but the SCORE scale risk of cardiac death was average. However, in 60 % of cases at life risks were not correctly assessed. Differences were found between the deceased depending on what type of locomotive they steered. Also, a part of SD victims overworked during the last month (year).Conclusion.Further improvement of work of medical service of JSC "Russian Railways" is necessary.

Postmortem chest computed tomography for the diagnosis of drowning: a feasibility study

It may be difficult to distinguish the cause of death in drowning cases without specific findings. The aim of this study was to explore the forensic value of thoracic postmortem computed tomography (PMCT) using routine images and three-dimensional (3D) image reconstructions. The imaging data of PMCT examinations of six drowning cadavers, aged 21–54 years, were analyzed. Twelve victims of sudden death from coronary artery disease (CAD) were chosen as a control group. After 3D bilateral lung images were reconstructed using image processing software, an interactive medical image control system was used to measure and analyze parameters including lung volume, lung volume ratio, mean CT value of the whole lung, and lung CT value distribution curves. Lung volume and lung volume ratio were used to assess the shape changes of the lung. Lung CT value distribution curves showed the corresponding number of pixels of the different CT values in the lung image. Lung volume was not significantly larger in drowning cases (mean 2 958 cm3) than in controls (mean 2 342 cm3). Lung volume ratio values in the drowning group (mean 0.3156) were greater than those in the control group (mean 0.2763); (P = 0.02). There was no significant difference between the drowning and control group in the mean CT value of the whole lung. There were differences between lung CT value distribution curves in drowning victims and controls, with drowning victims showing a single peak and CAD cases showing a bimodal distribution. Thoracic PMCT is helpful for the forensic medical diagnosis of drowning. Lung volume ratio and lung CT value distribution are potential indicators to distinguish between drowning and CAD.

Sudden unexplained death due to cardiac arrest.

Sudden unexplained death due to cardiac arrest refers to a group of heterogeneous heart disorders characterized by sudden cessation of cardiac activity followed by hemodynamic collapse. It may be associated with structural heart disease or may occur in the absence of structural abnormalities. These inherited conditions increase the risk of sudden unexplained death in living relatives when there is a family history of sudden death. It is recommended to screen other family members of sudden unexplained death victims, as studies have revealed affected individuals in 40% of families. (www.actabiomedica.it)

Ani ölüm ve koroner kalp hastalığı: geriye dönük bir otopsi çalışması

Purpose: The aim of this study was to examine how often myocardial infarction in abruptly dying persons with or without known coronary heart disease could be found as well as to estimate the severity of atheromatosis in correlation to gender and age. Materials and Methods: A retrospective study was designed using data from clinical records of 184 cases of adults who submitted with sudden death and underwent autopsy during a period of one year. We studied the demographic characteristics, season and location of death. Symptoms, smoking, alcohol and drug use, circumstances of death were also record. Coronary arteries findings in autopsy, heart weight, localization of myocardial infarction and the presence of an old myocardial infraction were record from autopsy report. Results: 92 patients (54 male, 38 female mean aged 64.8 years) met the inclusion criteria. In the majority of cases an acute myocardial infraction was certified during autopsy (92.4%). Grading severity of coronary arteries lesions in most of cases they characterized as severe (75%), and only in two cases they found to be normal. Males were more possible to have moderate or severe lesions in coronary arteries compared with females. Severe atheromatosis was found in older victims more frequent compare to younger. Conclusions: Acute myocardial infarction is a common autopsy finding among victims of sudden cardiac death. Old-aged myocardial infraction also can be identified in many cases and the severity of atheromatic lesions extends by age.

Abstract 17416: miR-1468-3p Regulates Development of Cardiac Fibrosis

Background: Accumulation of extracellular matrix disturbs the electrical conduction and stiffens myocardium, leading to higher risk for arrhythmias and diastolic dysfunction. MicroRNAs (miRNAs) function in post-translational gene regulation, and aberrant alteration of miRNAs level has been implicated in cardiac pathologies. Methods and Results: RNA sequencing of RNA samples of sudden cardiac death (SCD) victims with idiopathic myocardial fibrosis (IMF) for differentially expressed miRNAs identified miR-1468-3p. qPCR analysis validated that expression of miR-1468-3p is upregulated in hearts of SCD victims with IMF comparing to control subjects. However, the role and molecular function of miR-1468-3p in cardiac fibrosis are not known. We utilized human cardiac fibroblasts (hCFs) and gain- and loss-of-function approaches to study the role of miR-1468-3p in modulating fibroblast function. Overexpressing miR-1468-3p in hCFs resulted in an increase in expression of several fibrotic genes compared with hCFs transfected with control mir-mimic. Western blot analysis showed that miR-1468-3p mimic was sufficient to drive expression of collagen I and CTGF protein expression. Treatment of hCFs with miR-1468-3p antagomir did not alter expression of fibrosis-related gene at basal level, whereas miR-1468-3p inhibition significantly attenuated TGF-β1-induced collagen I and collagen III expression. Treatment of hCFs with miR-1468-3p antagomir blunted TGF-β1-induced collagen I and CTGF protein expression, but not TGF-β1-induced αSMA expression. Employing Sirius Red/Fast Green assay, we validated that depletion of miR-1468-3p antagonized both TGF-β1-triggered collagen and non-collagen protein production. Finally, we found that miR-1468-3p antagomir downregulated TGF-β1-induced collagen expression partially through the interference of TGF-β1/MAPK signals (p38 and JNK) and Integrin signaling. Conclusions: Our data indicate a pro-fibrotic role of miR-1468-3p in modulating cardiac fibrosis, and manipulating the expression of miR-1468-3p may provide a therapeutic strategy for treatment of cardiac fibrosis.

Variability of the medullary arcuate nucleus in humans.

IntroductionThe arcuate nucleus is a component of the ventral medullary surface involved in chemoreception and breathing control. The hypoplasia of this nucleus is a very frequent finding in victims of sudden unexplained fetal and infant death (from the last weeks of pregnancy to the first year of life). On the contrary, this developmental alteration is rarely present in age‐matched controls who died of defined causes. These observations lead to hypothesize that a well‐developed and functional arcuate nucleus is generally required to sustain life. The aim of this study was to investigate whether the arcuate nucleus maintains the same supposed function throughout life.MethodsWe carried out neuropathological examinations of brainstems obtained from 25 adult subjects, 18 males and 7 females, aged between 34 and 89 years, who died from various causes.ResultsFor almost half of the cases (44%) microscopic examinations of serial histological sections of medulla oblongata showed a normal cytoarchitecture of the arcuate nucleus, extending along the pyramids. For the remaining 56% of cases, various degrees of hypodevelopment of this nucleus were observed, validated through the application of quantitative morphometric investigations, from decreased area, neuron number and volume, to full aplasia.ConclusionsThese unexpected findings indicate that the involvement of the arcuate nucleus in chemoreception in adulthood is questionable, given the possibility of living until late age without this nucleus. This opens new perspectives for researchers on the role and function of the arcuate nucleus in humans from birth to old age.

Under-reporting of sudden unexpected death in epilepsy.

The identification and characterization of sudden unexpected deaths in epilepsy (SUDEP) may be improved, helping to optimize prevention and intervention. We set out to assess the frequency and demographic and clinical characteristics of SUDEP cases in a sudden death cohort. All out-of-hospital deaths were investigated from March 1, 2013 to February 28, 2015 in Wake County, NC, attended by the Emergency Medical Services. Cases were screened and adjudicated by three physicians to identify sudden death cases from any cause among free-living adults, aged 18-64. In total, 399 sudden death victims were identified during this two-year period. Seizure history, demographic and clinical characteristics, and healthcare utilization patterns were assessed from death records, emergency response scene reports, and medical records. Sudden death cases with a history of seizures were summarized by an experienced chart abstractor (SC) and adjudicated by an experienced neurologist (OD). We then compared demographic and clinical characteristics and healthcare utilization patterns of neurologist-identified SUDEP cases to other sudden death victims in our population-based registry of sudden death from any cause. SUDEP accounted for 5.3% of sudden deaths. However, seizures or complications of seizures were only considered the primary cause of death on death certificates in 1.5% of sudden deaths. SUDEP cases were more likely to have a history of alcohol abuse. Mental health disorders and a low level of medication compliance and healthcare utilization were common among SUDEP victims. SUDEP accounts for approximately 5.3% of sudden deaths from any cause in individuals aged between 18 and 64. Death certificates underestimate the burden of sudden death in epilepsy, attributing only 1.5% of sudden deaths to seizures or complications of seizures. Accurate documentation of epileptic disorders on death certificates is essential for the surveillance of SUDEP. Further, interventions that promote better use of medical services and patient engagement with healthy living practices may reduce sudden deaths in epilepsy.

5048Electrocardiographic and pathologic changes in young sudden death victims affected with arrhythmogenic cardiomyopathy: a clinic-pathology study

5048Electrocardiographic and pathologic changes in young sudden death victims affected with arrhythmogenic cardiomyopathy: a clinic-pathology study

Recommendations for genetic testing and counselling after sudden cardiac death: practical aspects for Swiss practice.

There is a need to standardise, within a coordinated Swiss framework, the practical aspects of genetic testing and genetic counselling on possibly inherited cardiovascular disorders in relatives of a sudden cardiac death (SCD) victim. Because of the major advances in genetic investigation techniques and recent publication of international guidelines in the field of cardiology, genetics and pathology, we consider it important to summarise the current evidence and propose an optimal approach to post-mortem genetic investigation for SCD victims and their families in Switzerland. In this article, we discuss important technical, financial and medico-ethical aspects, and provide updated information on specific situations in which forensic pathologists, general practitioners and cardiologists should suspect a genetic origin of the SCD. At present, the principles of benefit, the duty to warn and the impact of genetic information for family members at risk are considered as strong justifications for post-mortem disclosure and prevail over the arguments of respect for a deceased person's privacy and confidentiality. This paper underlines also the need to update and improve the general knowledge concerning the genetic risk of cardiovascular pathologies, the importance to perform an autopsy and post-mortem genetic testing in SCD victims, and to develop standardized post-mortem disclosure policy at national and international levels for SCD cases and relatives.

Recommendations for genetic testing and counselling after sudden cardiac death: practical aspects for Swiss practice.

There is a need to standardise, within a coordinated Swiss framework, the practical aspects of genetic testing and genetic counselling on possibly inherited cardiovascular disorders in relatives of a sudden cardiac death (SCD) victim. Because of the major advances in genetic investigation techniques and recent publication of international guidelines in the field of cardiology, genetics and pathology, we consider it important to summarise the current evidence and propose an optimal approach to post-mortem genetic investigation for SCD victims and their families in Switzerland. In this article, we discuss important technical, financial and medico-ethical aspects, and provide updated information on specific situations in which forensic pathologists, general practitioners and cardiologists should suspect a genetic origin of the SCD. At present, the principles of benefit, the duty to warn and the impact of genetic information for family members at risk are considered as strong justifications for post-mortem disclosure and prevail over the arguments of respect for a deceased person's privacy and confidentiality. This paper underlines also the need to update and improve the general knowledge concerning the genetic risk of cardiovascular pathologies, the importance to perform an autopsy and post-mortem genetic testing in SCD victims, and to develop standardized post-mortem disclosure policy at national and international levels for SCD cases and relatives.

Determination of cocaine, metabolites and a crack cocaine biomarker in whole blood by liquid–liquid extraction and UHPLC–MS/MS

Cocaine is a potent stimulant drug widely abused that exists in two forms: as a hydrochloride salt and as a free base (crack). Cocaine and the inactive metabolite benzoylecgonine can be determined to reveal any kind of cocaine use, whereas the pyrolysis product anhydroecgonine methyl ester (AEME) can be determined to reveal crack smoking. There are many bioanalytical LC–MS/MS methods used for the determination of cocaine, metabolites and AEME. In these methods, chromatographic separation is usually performed by HPLC and sample preparation by solid phase extraction. For the first time, an UHPLC–MS/MS method for the simultaneous determination of cocaine, benzoylecgonine, cocaethylene and AEME in blood using a sample preparation by liquid–liquid extraction was developed and validated. Extraction recoveries were approximately 80%, 40%, 80% and 80%, respectively, obtained by using a mixture of MTBE/2-propanol (70:30, v:v). Chromatographic separation was performed on a core shell biphenyl UHPLC column (100×2.1mm ID, 1.7μm particles). Method validation showed that the method is precise, accurate, robust and sensitive for its purposes. Limit of quantification (LOQ) concentrations were 0.7–1.5ng/mL. The method was used to determine cocaine, benzoylecgonine, cocaethylene and AEME in 22 blood samples collected from victims of sudden, unexpected or violent death in Sao Paulo (Brazil). Concentrations ≥LOQ were observed in 19, 21, 10 and 10 of these samples, respectively.

El grosor y una expresión de miARN alterada en la grasa epicárdica se asocian con enfermedad coronaria en víctimas de muerte súbita

Introduction and objectivesAn increased epicardial adipose tissue (EAT) thickness has become a new risk factor for coronary heart disease (CHD). We aimed to study the role of EAT dysfunction as a CHD marker by focusing on its thickness and microRNA (miRNA) expression profile, and the potential factors possibly influencing them. MethodsOne hundred and fifty-five CHD sudden cardiac death victims and 84 non–CHD-sudden death controls were prospectively enrolled at autopsy. A representative subset underwent EAT thickness measurements and EAT miRNA expression profiling. ResultsEpicardial adipose tissue thickness was increased and allowed an accurate diagnosis of patient status (among other measurements, EAT score area under the curve 0.718, P < .001). Epicardial adipose tissue from patients showed 14 up- and 14 down-regulated miRNAs and miR-34a-3p, -34a-5p, -124-3p, -125a-5p, 628-5p, -1303 and -4286 were validated by quantitative real-time polymerase chain reaction. Patients exhibited higher EAT levels of miR-34a-3p and -34a-5p than controls (with a positive trend considering EAT from coronaries without stenosis, with stable stenosis and complicated plaques) and correlated with age only in controls. The mild positive correlation between liver and EAT miR-34a-5p levels in patients (r = 0.295, P = .020) dramatically increased in EAT from complicated plaques (r = 0.799, P = .017). Similar correlations were observed for high-sensitivity-C-reactive protein levels and miR-34a-5p levels both in EAT and liver extracts. ConclusionsIncreased age-independent levels of miR-34a-3p and -34a-5p characterize the EAT miRNA expression profile of CHD regardless of EAT thickness, anthropometric parameters, and the presence of underlying atherosclerotic plaques.Full English text available from: www.revespcardiol.org/en

Sudden coronary death in the young: Evidence of contractile phenotype of smooth muscle cells in the culprit atherosclerotic plaque

BackgroundCulprit coronary atherosclerotic plaques (APs) from young sudden cardiac death (SCD) victims are mostly non-atheromatous, i.e., consisting of proliferative smooth muscle cells (SMCs). Coronary vasospasm has been advocated to explain plaque instability in the absence of thrombosis. Our aim was to characterize the SMC phenotype in the intima and media of coronary arteries from young SCD victims. Methods and ResultsA total of 38 coronary artery segments were studied: (a) 18 APs from young (≤40 years old) SCD patients, (b) 9 APs from old (>40 years old) SCD patients, (c) 11 non-atherosclerotic coronary arteries from young patients (≤40 years old). Markers of differentiated SMCs such as α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chains (SMMHCs), and heavy-caldesmon (h-CaD), were assessed in intima and media by immunohistochemistry and quantified morphometrically. In the intima, their expression was higher in non-atherosclerotic arteries (44.37 ± 3.03% for α-SMA, 14.21 ± 2.01% for SMMHCs, 8.90 ± 1.33% for h-CaD) and APs from young SCD victims (38.95 ± 2.29% for α-SMA, 11.92 ± 1.92% for SMMHCs, 8.93 ± 1.12% for h-CaD) compared with old patients (22.01 ± 3.56% for α-SMA, 6.39 ± 0.7% for SMMHCs, 3.00 ± 0.57% for h-CaD; all P statistically significant). The media of non-atherosclerotic arteries and APs from young SCD victims exhibited strong positivity for the differentiation markers unlike that of old patients. ConclusionsSMCs of coronary APs as well as from the underlying media from young SCD victims exhibit strong contractile phenotype. In the setting of critical stenosis, both intima and media SMC contractility might contribute to transient coronary spasm leading to myocardial ischemia and SCD.

Recognizing rare cardiac diseases by electrocardiogram

A number of rare cardiac diseases can be recognized by electrocardiogram (ECG). This article illustrates the clinical importance of ECG as a key diagnostic tool to detect Wolff-Parkinson-White syndrome and channelopathies, which are frequently diagnosed late after one or more affected family members have become victims of sudden cardiac death. These channelopathies include long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. In addition, typical ECG findings are frequently present in patients with idiopathic ventricular tachycardia, arrhythmogenic right ventricular dysplasia, digitalis intoxication, hyperkalemia, acute cor pulmonale due to pulmonary embolism, as well as severe left ventricular hypertrophy as in hypertrophic cardiomyopathy.

Abstract P028: High Framingham General Cardiovascular Disease Risk Scores in Victims of Out of Hospital Sudden Death

Introduction: Individuals with a history of cardiovascular disease (CVD) have a high risk of out-of-hospital sudden unexpected death (OHSUD). However, most OHSUDs occur in victims without a prior history of CVD. Information on CVD risk in these victims is scarce. Hypothesis: We hypothesized that OHSUD victims who had no prior diagnosis of CVD have higher 10-year CVD risk compared to a matched living control population. Methods: OHSUD cases were adjudicated from all emergency medical service attended out-of-hospital deaths aged 30-64 in Wake County, NC between 2013-2015. Age group and gender-matched controls were randomly selected from Wake County residents who visited a local healthcare facility over the same period (~3:1 match ratio). We obtained two years of medical records prior to death (cases) or last visit (controls). After excluding individuals with a history of CVD, we calculated the 10-year risk of CVD for each subject using the published general CVD algorithms by D'Agostino et al. Risk was classified into low (&lt;6%), moderate (6%-20%), and high (&gt;20%). Results: Among subjects without CVD, we included 106 cases and 414 controls who had sufficient data for calculating Framingham risk score. Gender distribution was similar in both case and control groups. The average 10-year risk of CVD was higher for OHSUDs than controls (29% vs. 16%, p=&lt;0.0001). Similar results were found in both men (34% vs. 19%, p=&lt;0.0001) and women (11% vs. 7.3%, p=0.0005). A larger proportion of OHSUDs were considered “high risk” compared to controls (57% (60 of 106) vs. 28% (114 of 414), p=&lt;0.001). This finding remained significant when stratified by gender (Figure). Conclusion: The majority of out of hospital sudden death victims without known CVD are at high risk of cardiovascular disease. This finding bolsters the essential role of office-based risk assessment tools in identifying high risk patients antemortem. Targeted interventions for intensive CVD risk reduction may lead to a decrease in sudden deaths.

Outcome of clinical management in relatives of sudden cardiac death victims

BackgroundInternational guidelines recommend clinical assessment of the surviving first-degree relatives of sudden cardiac death (SCD) victims to identify a probable cause of death and protect surviving relatives. Only few studies have reported the outcome of clinical management and follow-up of relatives to SCD victims. MethodsWe performed a retrospective cohort study of the clinical and genetic assessment of surviving relatives of SCD victims referred to the Clinic of Inherited Cardiac Diseases at Aarhus University Hospital, Denmark, between 1995 and 2016. We studied clinical and autopsy findings on all cases of SCD among children and adults. Relatives were followed for adverse cardiovascular events including cardiac hospitalization, new-onset heart failure, coronary heart disease, malignant syncope or documented malignant ventricular arrhythmias, and death. ResultsWe included 292 relatives of 56 SCD victims. During a median (interquartile range) follow-up of 3.3 (1.6–4.7) years twelve relatives experienced an adverse cardiovascular event of which only five were related to the inherited cardiac disease in the family. One developed dilated cardiomyopathy and one tachycardia induced heart failure, five suffered from ventricular tachycardia or a malignant syncope and received a secondary prophylactic Implantable Cardioverter Defibrillator, three had a coronary heart disease event and two died from old age. ConclusionRelatives of SCD victims have a low rate of adverse cardiac events when guideline-based assessment and care is applied.

Global ECG Measures and Cardiac Structure and Function: The ARIC Study (Atherosclerosis Risk in Communities).

Electric excitation initiates myocardial mechanical contraction and coordinates myocardial pumping. We hypothesized that ECG global electric heterogeneity (GEH) and its longitudinal changes are associated with cardiac structure and function. Participants from the ARIC study (Atherosclerosis Risk in Communities) (N=5114; 58% female; 22% blacks) with resting 12-lead ECGs (visits 1-5) and echocardiographic assessment of left ventricular (LV) ejection fraction, LV global longitudinal strain, LV mass index, LV end-diastolic volume index, and LV end-systolic volume index at visit 5 were included. Longitudinal analysis included ARIC participants (N=14 609) with measured GEH at visits 1 to 4. GEH was quantified by spatial ventricular gradient, QRS-T angle, and sum absolute QRS-T integral. Cross-sectional and longitudinal regressions were adjusted for manifest and subclinical cardiovascular disease. Having 4 abnormal GEH parameters was associated with a 6.4% (95% confidence interval, 5.5-7.3) LV ejection fraction decline, a 24.2 g/m2 (95% confidence interval, 21.5-26.9) increase in LV mass index, a 10.3 mL/m2 (95% confidence interval, 8.9-11.7) increase in LV end-diastolic volume index, and a 7.8 mL/m2 (95% confidence interval, 6.9-8.6) increase in LV end-systolic volume index. Altogether, clinical and ECG parameters accounted for approximately one third of LV volume and 20% of systolic function variability. The associations were significantly stronger in cardiovascular disease. Sum absolute QRS-T integral increased by 20 mV*ms for each 3-year period in participants who demonstrated LV dilatation at visit 5. Sudden cardiac death victims demonstrated rapid GEH worsening, whereas those with LV dysfunction demonstrated slow GEH worsening. Healthy aging was associated with a distinct pattern of spatial ventricular gradient azimuth decrement. GEH is a marker of subclinical abnormalities in cardiac structure and function.

Thickness and an Altered miRNA Expression in the Epicardial Adipose Tissue Is Associated With Coronary Heart Disease in Sudden Death Victims

Introduction and objectivesAn increased epicardial adipose tissue (EAT) thickness has become a new risk factor for coronary heart disease (CHD). We aimed to study the role of EAT dysfunction as a CHD marker by focusing on its thickness and microRNA (miRNA) expression profile, and the potential factors possibly influencing them. MethodsOne hundred and fifty-five CHD sudden cardiac death victims and 84 non–CHD-sudden death controls were prospectively enrolled at autopsy. A representative subset underwent EAT thickness measurements and EAT miRNA expression profiling. ResultsEpicardial adipose tissue thickness was increased and allowed an accurate diagnosis of patient status (among other measurements, EAT score area under the curve 0.718, P < .001). Epicardial adipose tissue from patients showed 14 up- and 14 down-regulated miRNAs and miR-34a-3p, -34a-5p, -124-3p, -125a-5p, 628-5p, -1303 and -4286 were validated by quantitative real-time polymerase chain reaction. Patients exhibited higher EAT levels of miR-34a-3p and -34a-5p than controls (with a positive trend considering EAT from coronaries without stenosis, with stable stenosis and complicated plaques) and correlated with age only in controls. The mild positive correlation between liver and EAT miR-34a-5p levels in patients (r = 0.295, P = .020) dramatically increased in EAT from complicated plaques (r = 0.799, P = .017). Similar correlations were observed for high-sensitivity-C-reactive protein levels and miR-34a-5p levels both in EAT and liver extracts. ConclusionsIncreased age-independent levels of miR-34a-3p and -34a-5p characterize the EAT miRNA expression profile of CHD regardless of EAT thickness, anthropometric parameters, and the presence of underlying atherosclerotic plaques.

Obesity and sudden cardiac death in the young: Clinical and pathological insights from a large national registry.

Aims Obesity is an increasing public health problem and a risk factor for cardiovascular diseases. The aim of the study was to determine the main features and aetiologies in a large cohort of sudden cardiac deaths that occurred in obese subjects. Methods Between 1994 and 2014, 3684 consecutive cases of unexpected sudden cardiac death were referred to our cardiac pathology centre. This study was confined to young individuals (age ≤ 35 years) for whom information about body mass index was available and consisted of 1033 cases. Results Two-hundred and twelve individuals (20%) were obese. In obese sudden cardiac death victims the main post-mortem findings were: normal heart (sudden arrhythmic death syndrome) ( n = 108; 50%), unexplained left ventricular hypertrophy ( n = 25; 12%) and critical coronary artery disease ( n = 25; 12%). Less common were hypertrophic cardiomyopathy ( n = 4; 2%) and arrhythmogenic right ventricular cardiomyopathy ( n = 4;2%). When compared with non-obese sudden cardiac death victims, sudden arrhythmic death syndrome was less common (50% vs. 60%, P < 0.01), whereas left ventricular hypertrophy and critical coronary artery disease were more frequent (12% vs. 2%, P < 0.001 and 12% vs. 3%, P < 0.001, respectively). The prevalence of critical and non-critical coronary artery disease was significantly higher in obese individuals (23% vs. 10% in non-obese individuals, P < 0.001). Conclusions Various conditions underlie sudden cardiac death in obesity, with a prevalence of sudden arrhythmic death syndrome, left ventricular hypertrophy and coronary artery disease. The degree of left ventricular hypertrophy measured by heart weight is excessive even after correction for body size. Almost one in four young obese sudden death patients show some degree of coronary artery disease, underscoring the need for primary prevention in this particular subgroup.