Sudden Arrhythmic Death Syndrome Research Articles

Sudden Intrauterine Unexplained Death (SIUD) and Oxidative Stress: Placental Immunohistochemical Markers.

Intrauterine fetal death and perinatal death represent one of the most relevant medical scientific problems since, in many cases, even after extensive investigation, the causes remain unknown. The considerable increase in medical legal litigation in the obstetrical field that has witnessed in recent years, especially in cases of stillborn births, has simultaneously involved the figure of the forensic pathologist in scientific research aimed at clarifying the pathophysiological processes underlying stillbirth. our study aims to analyze cases of sudden intrauterine unexplained death syndrome (SIUD) to evaluate the role of oxidative stress in the complex pathogenetic process of stillbirth. In particular, the immunohistochemical expression of specific oxidative stress markers (NOX2, NT, iNOS, 8-HODG, IL-6) was evaluated in tissue samples of placentas of SIUDs belonging to the extensive case series (20 cases), collected from autopsy cases of the University of Ferrara and Politecnica delle Marche between 2017 and 2023. The study demonstrated the involvement of oxidative stress in intrauterine fetal deaths in the placenta of the cases examined. In SIUD, the most expressed oxidative stress markers were NOX2 and 8-HODG. The study contributes to investigating the role of oxidative stress in modulating different pathways in unexplained intrauterine fetal death (SIUD) tissues.

Genetic and clinical characteristics of catecholaminergic polymorphic ventricular tachycardia in a Taiwanese nationwide cohort

BackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and lethal arrhythmia. Ryanodine receptor 2 (RYR2) mutation accounts for ∼60% of CPVT patients which is inherited in an autosomal dominant pattern. ObjectiveThis study aimed to identify CPVT-related mutations and clinical characteristics among Taiwanese CPVT patients and compare to other cohorts worldwide. MethodsClinical and genetic data were obtained from the Sudden Arrhythmia Death Syndrome Registry in Taiwan (SADS-TW). Forty clinically diagnosed Taiwanese CPVT patients were included. ResultsThis is the first nationwide CPVT cohort in Taiwan. Among the 29 Taiwanese patients with CPVT-related gene mutations, 55% had RYR2 mutations, a rate similar to other ethnicities. Three out of 12 RYR2 variants were unreported. Exercise-induced symptoms including syncope and cardiac arrest were more frequent in East Asian cohorts (Taiwanese 79%, Japanese 91%), compared to Caucasian cohorts (59%) (p = 0.002). ConclusionThe discovery of diverse RYR2 mutations in the Taiwanese CVPT population demonstrates the importance of genetic testing in different ethnicities.

Proarrhythmic drugs, drug levels, and polypharmacy in victims of sudden arrhythmic death syndrome: An autopsy-based study from Denmark

BackgroundSudden arrhythmic death syndrome (SADS), characterized by an unknown or inconclusive cause of death at autopsy together with a negative or nonlethal toxicology screening result, is the most common cause of sudden cardiac death in victims younger than 35 years. The complete causality of SADS remains unclear, with drugs being a potential risk factor. ObjectiveThis study aimed to describe the toxicologic profiles of SADS victims, focusing on proarrhythmic drugs, drug levels, and polypharmacy. MethodsAll deaths in Denmark of those aged 1–35 years in 2000–2019 and 36–49 years in 2007–2019 were examined through death certificates, national registries, and autopsy reports with toxicology screenings. We investigated all sudden unexpected death victims with an autopsy performed, including negative or nonlethal drug findings, where cause of death was unknown or inconclusive (SADS). ResultsWe identified 477 SADS victims; 313 (66%) had a positive toxicology screening result (adjudicated nonlethal), with an average of 2.8 drugs per case. More than half of the SADS victims with a positive toxicology screening result had QT-prolonging or brugadogenic drugs present. Polypharmacy was present in 66%, psychotropic polypharmacy in 37%, and QT-prolonging polypharmacy in 22%, with the most frequent overall and QT-prolonging drug combination being an antipsychotic and a psychoanaleptic drug. QT-prolonging drugs were more often present at suprapharmacologic levels than non–QT-prolonging drugs. ConclusionThe majority of the SADS population had a positive toxicology screening result, with a notably large proportion having proarrhythmic drugs and polypharmacy. This highlights the need for future focus on drugs as a risk factor for SADS.

Ethnicity and sudden cardiac death in athletes: insights from a large United Kingdom registry.

The relationship between ethnicity and causes of sudden cardiac death (SCD) in athletes is poorly understood. To investigate aetiology of SCD among different ethnicities in a large cohort of athletes. Between 1994 and November 2022, 7880 cases of SCD were consecutively referred from all over the United Kingdom to our national cardiac pathology centre; 848 (11%) were athletes. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners. Most of athletes were white (n = 758; 89%). Black and Asian athletes were in number of 51 (6%) and 39 (5%), respectively. A structurally normal heart, indicative of sudden arrhythmic death syndrome (SADS) was the most common autopsy finding (n = 385; 45%), followed by myocardial diseases (n = 275; 32%), atherosclerotic coronary artery disease (CAD) (n = 58; 7%), and coronary artery anomalies (n = 29; 3%). In most of cases, death occurred during exercise (n = 737; 87%). Arrhythmogenic cardiomyopathy (ACM) was more common in black (n = 13; 25%) than in white (n = 109; 14%) and Asian (n = 3; 8%) athletes (P = 0.03 between black and white athletes; P = 0.04 between black and Asian athletes); in contrast, CAD was more common in Asians (n = 6; 15% vs. n = 51; 7% in whites vs. n = 1; 2%; in blacks, P = 0.02 between Asian and black athletes). Among white athletes, ACM was more common in individuals who died during exercise than in the ones who died at rest (P = 0.005). Such a difference was not observed in Asian and black athletes. In Asian athletes, CAD was the diagnosis at autopsy in 18% of individuals who died during exercise and in none of individuals who died at rest. A structurally normal heart at autopsy and myocardial diseases are the most common findings in athletes who died suddenly. While ACM is more common in black athletes, atherosclerotic CAD is more common in Asian athletes, with a strong association with exercise-induced SCD. ACM appears to be a driver of exercise-induced SCD in white athletes, however this is not the case in black and Asian athletes.

Diversity of ICD-10 coding for sudden arrhythmic death syndrome is likely to create a spurious rise in cases under new ICD-11 nomenclature

Diversity of ICD-10 coding for sudden arrhythmic death syndrome is likely to create a spurious rise in cases under new ICD-11 nomenclature

Incidence of quadricuspid pulmonary valves at postmortem examination

Quadricuspid pulmonic valve is a rare congenital abnormality and because of its difficult non-invasive assessment, it is usually discovered incidentally at autopsies (reported prevalence in post-mortem specimens ranges from 1 in 400 to 1 in 2000). Unlike a bicuspid pulmonary valve, it rarely presents with clinical complications, such as valvular insufficiency or stenosis. Abnormal function is rarely reported in cases that are not associated with other congenital heart disease. With increased sophistication of imaging coincidental quadricuspid valves autopsy studies are important to understand the anatomical consequences of this finding. Our case series identified 21 QPV cases from the Victorian Institute of Forensic Medicine, Melbourne and St George's University of London, Department of Cardiovascular Pathology. Cases were identified through local database searches and review of autopsy/cardiac examination reports over a 20-year period. Available photographs were also systematically examined. Fifteen cases had causes of death with no direct causality to cardiac valvular pathology alone. Six cases were considered unascertained or similar (sudden arrhythmic death syndrome and sudden unexpected death in epilepsy). The presence of QPV in these instances were uncertain but thought to be unlikely contributory to death, due to the absence of pulmonary valvular complications.

Seasonal Variation in Sudden Cardiac Death: Insights from a Large United Kingdom Registry

BackgroundSudden cardiac death (SCD) is relatively common and may occur in apparently healthy individuals. The role of seasonal variation as a risk factor for SCD is poorly understood. The aim of this study was to investigate whether SCD exhibits a predilection for specific seasons. MethodsWe reviewed a database of 4751 cases of SCD (mean age 38 ± 17 years) referred to our Center for Cardiac Pathology at St George’s University of London between 2000 and 2018. Clinical information was obtained from referring coroners who were asked to complete a detailed questionnaire. All cases underwent macroscopic and histological evaluation of the heart, by expert cardiac pathologists. ResultsSCD was more common during winter (26%) and rarer during summer (24%), p = 0.161. Significant seasonal variation was not observed among cases of sudden arrhythmic death syndrome (SADS, 2910 cases) in which the heart is structurally normal. In contrast, a significant difference in seasonal distribution among decedents exhibiting cardiac structural abnormalities at the post-mortem examination (n = 1841) was observed. In this subgroup, SCDs occurred more frequently during winter (27 %) compared to summer (22%) (p = 0.007). In cases diagnosed with a myocardial disease (n = 1399), SCD was most common during the winter (27%) and least common during the summer (22%) (p = 0.027). ConclusionsWhile SADS occurs throughout the year with no seasonal variation, SCD due to structural heart disease appears to be more common during the winter. Bio-meteorological factors may be potential triggers of SCD in individuals with an underlying structural cardiac abnormality.

Diabetes Epidemic- Heart Health & Homoeopathy

The famous singer KK died of heart attack, another TV actor died of heart attack. All these deaths are relatively at a younger age. In recent times, there has been a rise of such cases of sudden heart attacks & it is essential to understand the cause. There is a clear link between uncontrolled sugar levels & neuropathy. This phenomenon leads to masking of heart attack symptoms thus resulting in unexpected deaths. These are actually sudden cardiac arrest or arrhythmic death syndrome [3].

Epidemiology of Sudden Unexplained Death Syndrome among Southeast Asian Labor in Taiwan

Epidemiology of Sudden Unexplained Death Syndrome among Southeast Asian Labor in Taiwan

Editorial introductions.

Editorial introductions.

National sudden cardiac death autopsy database highlighting sudden arrhythmic death and cardiomyopathies, applying diagnostic criteria and expanding the concept of the molecular autopsy

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Cardiac Risk in the Young Background Sudden cardiac death (SCD) is defined as natural unexpected death in witnessed cases occurring <1 hour and in unwitnessed cases as last seen alive <24hours. SCD due to ischaemic heart disease (IHD) is frequent in older age groups, in younger people genetic cardiac causes including channelopathies and cardiomyopathies are more frequent. Purpose To present the causes of SCD from a large pathology registry. Methods Cases were examined macroscopically and microscopically by two expert cardiac pathologists. Criteria used are presented in figure 1. Results The hearts from 7214 SCD cases were examined between 1994-2021. Sudden arrhythmic death syndrome (SADS), a morphologically normal heart, which can be underlain by the channelopathies, is most common (3821, 53%) followed by the cardiomyopathies (1558, 22%), then IHD (670, 9%). Valve disease (225, 3%), congenital heart disease (213, 3%) and myocarditis/sarcoidosis (206, 3%) are the next most common. Hypertensive heart disease (185, 3%), aortic disease (129, 2%), vascular disease (97, 1%) and conduction disease (40, 1%) are smaller proportions (figure 2). Discussion This is the largest SCD cohort with autopsy findings ever reported from one country. SADS and cardiomyopathies predominate. This study highlights the importance of the autopsy in SCD which is a significant public health concern in all age groups. Knowing the true incidence in our population will improve risk stratification and develop preventative strategies for family members. There is now a national pilot study integrating molecular autopsy into the assessment of SCD victims.

Post-mortem genetic testing in sudden cardiac death and genetic screening of relatives at risk: lessons learned from a Czech pilot multidisciplinary study

Sudden cardiac death (SCD) might have an inherited cardiac condition background. Genetic testing supports post-mortem diagnosis and screening of relatives at risk. Our aim is to determine the feasibility of a Czech national collaboration group and to establish the clinical importance of molecular autopsy and family screening. From 2016 to 2021, we have evaluated 100 unrelated SCD cases (71.0% males, age: 33.3 (12.8) years). Genetic testing was performed by next-generation sequencing utilizing a panel of 100 genes related to inherited cardiac/aortic conditions and/or whole exome sequencing. According to autopsy, cases were divided into cardiomyopathies, sudden arrhythmic death syndrome, sudden unexplained death syndrome, and sudden aortic death. We identified pathogenic/likely pathogenic variants following ACMG/AMP recommendations in 22/100 (22.0%) of cases. Since poor DNA quality, we have performed indirect DNA testing in affected relatives or in healthy parents reaching a diagnostic genetic yield of 11/24 (45.8%) and 1/10 (10.0%), respectively. Cardiological and genetic screening disclose 83/301 (27.6%) relatives at risk of SCD. Genetic testing in affected relatives as starting material leads to a high diagnostic yield offering a valuable alternative when suitable material is not available. This is the first multidisciplinary/multicenter molecular autopsy study in the Czech Republic which supports the establishment of this type of diagnostic tests. A central coordinator and proper communication among centers are crucial for the success of a collaboration at a national level.

Sudden arrhythmic death and cardiomyopathy are important causes of sudden cardiac death in the UK: results from a national coronial autopsy database.

Sudden cardiac death (SCD) is defined as natural unexpected death in witnessed cases occurring < 1h and in unwitnessed cases as last seen alive < 24h. SCD due to ischaemic heart disease (IHD) is frequent in older age groups; in younger people genetic cardiac causes, including channelopathies and cardiomyopathies, are more frequent. This study aimed to present the causes of SCD from a large specialist pathology registry. Cases were examined macroscopically and microscopically by two expert cardiac pathologists. The hearts from 7214 SCD cases were examined between 1994 and 2021. Sudden arrhythmic death syndrome (SADS), a morphologically normal heart, which can be underlaid by cardiac channelopathies, is most common (3821, 53%) followed by the cardiomyopathies (1558, 22%), then IHD (670, 9%), valve disease (225, 3%), congenital heart disease (213, 3%) and myocarditis/sarcoidosis (206, 3%). Hypertensive heart disease (185, 3%), aortic disease (129, 2%), vascular disease (97, 1%) and conduction disease (40, 1%) occur in smaller proportions. To our knowledge, this is the largest SCD cohort with autopsy findings ever reported from one country. SADS and cardiomyopathies predominate. This study highlights the importance of the autopsy in SCD, which is a significant public health concern in all age groups. Knowing the true incidence in our population will improve risk stratification and develop preventative strategies for family members. There is now a national pilot study integrating molecular autopsy and family screening into the assessment of SCD victims.

Sudden Cardiac Death Among Adolescents in the United Kingdom

BackgroundCauses and precipitating factors of sudden cardiac death (SCD) in adolescents are poorly understood. ObjectivesThe authors sought to investigate the etiologies of SCD and their association with physical activity in a large cohort of adolescents. MethodsBetween 1994 and June 2022, 7,675 cases of SCD were consecutively referred to our national cardiac pathology center; 756 (10%) were adolescents. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners. ResultsA structurally normal heart, indicative of sudden arrhythmic death syndrome was the most common autopsy finding (n = 474; 63%). Myocardial diseases were detected in 163 cases (22%), including arrhythmogenic cardiomyopathy (n = 36; 5%), hypertrophic cardiomyopathy (n = 31; 4%), idiopathic left ventricular hypertrophy (n = 31; 4%), and myocarditis (n = 30; 4%). Coronary artery anomalies were identified in 17 cases (2%). Decedents were competitive athletes in 128 cases (17%), and 159 decedents (21%) died during exercise. Arrhythmogenic cardiomyopathy was diagnosed in 8% of athletes compared with 4% of nonathletes (P = 0.05); coronary artery anomalies were significantly more common in athletes (9% vs 1%; P < 0.001), as well as commotio cordis (5% compared with 1% in nonathletes; P = 0.001). The 3 main comorbidities were asthma (n = 58; 8%), epilepsy (n = 44; 6%), and obesity (n = 40; 5%). ConclusionsSudden arrhythmic death syndrome and myocardial diseases are the most common conditions diagnosed at autopsy in adolescent victims of SCD. Among causes of SCD, arrhythmogenic cardiomyopathy, coronary artery anomalies, and commotio cordis are more common in young athletes than in similar age sedentary individuals.

Association of Cardiac Electrical Disorders With KCND3 Gene Mutation.

Globally, cardiac channelopathies leading to electrical disorders are responsible for a significant number of sudden cardiac deaths without structural heart disease. Many genes encoding different ion channels in the heart were identified and their impairment was found to be associated with life-threatening cardiac abnormalities. KCND3, one of the genes expressed both in the heart and brain, is reported to have an association with Brugada syndrome, early-onset atrial fibrillation, early repolarization syndrome, and sudden unexplained death syndrome. KCND3 genetic screening could be a promising tool for functional studies for an understanding of the pathogenesis and genetic determinants of the above-mentioned electrical disorders.

Inherited arrhythmias: considerations for nurses

This article is the third instalment of the British Journal of Cardiac Nursing’s series on cardiac genetic concepts. Inherited arrhythmias are a group of conditions that affect the cardiac electrical system, typically resulting from changes in the way sodium, potassium or calcium ions are handled in the cell. Inherited arrhythmias can cause sudden cardiac death, especially in people who are undiagnosed and untreated. Most inherited arrhythmias are inherited in an autosomal dominant pattern. This article provides an overview of the aetiology, diagnosis, risk-management and treatment of patients with inherited arrhythmias at different ages and stages of life. The focus will be on inherited arrhythmias, specifically long QT, Brugada and catecholaminergic polymorphic ventricular tachycardia. There will be a brief mention of idiopathic ventricular fibrillation and sudden arrhythmic death syndrome.

Effects of mexiletine on a race-specific mutation in Nav1.5 associated with long QT syndrome.

Mutations in cardiac Nav1.5 have been associated with LQT syndrome, Brugada syndrome, and sudden arrhythmia death syndrome. Genetic studies showed that Nav1.5 mutations vary across race-ethnic groups. The Nav1.5 mutation P1090L was linked with familial long QT syndrome (LQTS) and was identified as an ethnic-specific variant in Asians. To explore the role of the P1090L in the LQT syndrome, we characterized the effects of the mutation on the Nav1.5 channel function. We found that the P1090L mutation altered the gating process of the channel and exhibited an enhanced window current. Treatment with mexiletine reversed the depolarization shift of the steady-state inactivation produced by the mutation. Mexiletine modified the recovery and development of inactivation of the mutation and reduced the mutated channel's availability. We characterized that the P1090L is a gain-of-function, the mutation presented a larger window current and increased channel availability. Treatment with mexiletine rescued the dysfunctional inactivation of the mutation. The results might potentially enable a mechanism-based approach to the treatment of LQTS.

A Presentation of Analyses of COVID-19 Vaccine Samples, Blood Samples, Urine Samples, Foot Bath Samples, Sitz Bath Samples, and Skin-Extract Samples

Some members of Korea Veritas Doctors of COVID-19 analyzed COVID-19 vaccines samples, blood samples, urine samples, foot bath samples, sitz bath samples, and skin extract samples from COVID-19 vaccinated and unvaccinated subjects. Among the objects analyzed were self-assembling micro-sized particles, probable Graphene Oxide (GO), and strands of micro-sized materials of diverse structures (probably small GO particles). Intermittently self-vibrating objects (probable GO particles) in the blood of the injected were presented. Slowly moving synthetic parasite-like objects in the blood of the injected and another object of a water ski-like fast moving object in the foot bath water were also presented. COVID-19 vaccines were known to contain programmable mRNA, GO and synthetic parasite-like objects. The effect of these materials in the blood is a widespread damage to everything inside the body including multiple organs. Those damaging effects are linked to endotheliitis, mitochondrial damage, microthrombosis, myocarditis, Sudden Adult Death Syndrome (SADS), human DNA changes and Genetically Modified Organism (GMO), prion disease and dementia, infertility and depopulation, Vaccine Aided Immune Deficiency Syndrome (VAIDS), reprogramming of innate immunity, cancer, RNA Replicons (i.e., replicating spike proteins forever as far as the host lives), and shedding by vaccinated people. Moreover, these materials may cause Vaccine-Induced Thrombotic Thrombocytopenia (VITT), and cytokine storms which is claimed to be typical COVID-19 symptoms. It can be easily argued that there is no other reason for the presence of these main components of COVID-19 vaccines including programmable mRNA, GO, and synthetic parasite-like objects, but to produce slow and painful death in people and to depopulate the world. Considering the hazardous effects of those GOs and other synthetic materials in the human body, human beings need to be detoxified from those hazardous materials and those extracted structures came out of human body need to be carefully treated and detoxified.

Brugada syndrome in Thailand: Three decades of progress.

Our group began investigating the cause of sudden unexplained death syndrome in Thailand in 1994 and found that among sudden unexplained death syndrome patients, the Brugada phenotype was ubiquitous. Following this important observation, Brugada syndrome (BrS) became our main research focus and has galvanized our collaboration with several global prominent scientists over the past 30 years. Through this collaborative research, we made major progress toward better understanding of the syndrome and gained knowledge in genetic background, pathophysiology, and new management. Two consensus reports were published to help define diagnostic criteria, risk stratification, and management of BrS patients. In this review, we share our experiences and progress of our research and development of our program that was designed to identify the cause of sudden death, understand pathophysiology of the syndrome, and develop effective and safe management and therapy of BrS patients. Although our work in Thailand was challenging at the beginning, it later blossomed into a multicollaborative research enterprise that has produced several important findings that have shed light on the pathophysiology of BrS and development of a new effective treatment modality, catheter ablation.

Causes of sudden cardiac death according to age and sex in persons aged 1–49 years

Knowledge of causes of sudden cardiac death (SCD) according to age is important in clinical decision making and to lower the risk of SCD in family members of the deceased. The purpose of this study was to report overall and sex-stratified causes of SCD according to age in persons aged 1-49 years. The study population consisted of all persons in Denmark aged 1-35 years in 2000-2009 and 36-49 years in 2007-2009, which equals 27.1 million person-years. Danish death certificates, discharge summaries, autopsy reports, and data from nationwide registries were used to identify all SCD cases. The SCD cases were divided into 5-year age groups. In the 10-year study period, there were 14,294 deaths, of which 1362 (10%) were classified as SCD. Potentially inherited cardiac disease accounted for a high proportion (43%-78%) of autopsied SCD in all age groups. A significant proportion (19%-54%) of SCD was caused by sudden arrhythmic death syndrome in all age groups. Autopsy rates in both sudden unexpected death cases and SCD cases declined significantly with increasing age (74% in the youngest age group vs 35% in the oldest). The proportion of SCD cases that were identified with a potentially inherited cardiac disease postmortem was high in all studied age groups, while autopsy rates in sudden and unexpected death cases declined markedly with increasing age. Our findings indicate that diagnoses of inherited heart disease are likely missed in some SCD cases, along with the opportunity for treatment and prevention in surviving relatives.