Sudden Cardiac Death In Young Research Articles

Sudden Cardiac Death in Young Age, What Should We Know?

While young sudden cardiac death (SCD) is statistically uncommon, its dramatic presentation and impact on families and communities make it a newsworthy issue. Nonetheless, it is important to view SCD in children and adolescents as a public health concern and devise strategies based on research and consensus to address it. Both individuals with and without a history of cardiovascular illness are susceptible to sudden cardiac death. Employing cardiovascular disease risk screening for healthy individuals and those with a family history of sudden cardiac death can serve as a preventive approach against sudden cardiac death. Assessing the severity of cardiovascular disease in people becomes essential to prevent disease progression and minimize the risk of mortality from cardiovascular conditions. Keyword: Young, Sudden Cardiac Death, Preventive.

Sudden cardiac death in people with schizophrenia: higher risk, poorer resuscitation profiles and differing pathologies

Abstract Background People with schizophrenia account for approximately 1.0% of the population and appear to experience increased rates of sudden cardiac death (SCD). This study determined characteristics of increased SCD in people with schizophrenia. Methods A prospective state-wide registry compared people aged 15-50 years with and without schizophrenia who experienced SCD within a two-year time-period and were referred for forensic evaluation. Results 579 individuals were identified, of whom 65 (11.2%) had schizophrenia. Patients with schizophrenia were more commonly smokers (46.2% vs 23.0%, p<0.0001), consumed excess alcohol (32.3% vs 21.4%, p=0.05), and used QTc-prolonging medications (69.2% vs 17.9%, p<0.0001). They were less likely to arrest while exercising (0.0% vs 6.4%, p=0.04). Unfavourable arrest-related factors included lower rates of witnessed arrest (6.2% vs 23.5%, p<0.0001), more likely to be found in asystole (92.3% vs 73.3%, p<0.0001), and being more likely to be found as part of a welfare check after a prolonged period of time (median 42 vs 12 hours, p=0.003). There was more frequent evidence of decomposition, and they more commonly underwent autopsy (41.2% vs 26.4%, p=0.04 and 93.8% vs 82.5%, p=0.05), with diagnosis of non-ischaemic cardiomyopathy being more common (29.2% vs 18.1%, p=0.04). Conclusion People with schizophrenia account for 11% of young SCD patients referred for forensic investigations, exceeding population rates eleven-fold. They have higher pre-existing cardiac risk factor burden, unfavourable resuscitation profiles and higher rates of non-ischaemic cardiomyopathy. Strategies targeting biopsychosocial support may deliver not only psychological benefits but also help reduce unwitnessed cardiac arrest.

Abstract 14902: Prevalence and Characteristics of Myocarditis-Related Sudden Death in the General Population

Introduction: Myocarditis is a frequent cause of sudden cardiac death (SCD) in young individuals (<35 years), but the frequency of myocarditis in middle-aged (35-65 years) and older SCD victims (>65 years) is unclear. Objective: We aimed to investigate the prevalence and characteristics of myocarditis-related sudden death in the general population. Methods: Our study population is drawn from the Fingesture study, which has prospectively collected all out-of-hospital SCD cases from Northern Finland (population ~700,000) since 1998. As required by Finnish law, all sudden deaths undergo a medicolegal autopsy. All out-of-hospital sudden death cases in the community with a verified cardiac cause of death at autopsy are included in the Fingesture study. By 2017, the Fingesture study had collected data on 5,869 SCD victims. Results: In total, 60 SCD victims had evidence of acute myocarditis at autopsy (1.0% of all SCD cases). The mean age of SCD victims with myocarditis was 55.9±18.2, which was significantly lower than among the rest SCD victims (65.0±12.3; p<0.001). Myocarditis cases were also more often female in comparison to the rest SCD cases (33.3% vs. 21.0%; p=0.02). The proportion of myocarditis was highest among young (<35 years) SCD cases (n=6/73; 8.2%), and the proportion decreased in middle aged (35-65 years) (n=34/2,948; 1.2%) and older (>65 years) SCD cases (n=20/2,848; 0.7%) (p<0.001), although the absolute number was higher. The most common diagnosis was undetermined acute myocarditis (n=42/60; 70%) followed by infective myocarditis (n=10/60; 16.7%) and pericarditis (n=5/60; 8.3%). In addition, two SCD cases had sarcoidosis and one had giant cell myocarditis. Five SCD cases due to myocarditis (8.3%) occurred during physical exercise. Conclusions: Myocarditis is a rare cause of SCD in the general population. Although the relative proportion of myocarditis was highest among young SCD victims, the absolute number was highest among middle-aged SCD victims.

Differences among young unwitnessed sudden cardiac death, according to time from last seen alive: Insights from a 15-year nationwide study

More than half of all sudden cardiac deaths (SCD) are unwitnessed, but the composition of the unwitnessed SCD population is poorly described. This study aimed to compare clinical and autopsy characteristics of young unwitnessed SCD, depending on the time from last contact to being found dead. All unwitnessed SCD aged 1-35 years in Denmark from 2000-2014 identified through a multi-source approach were included. Time from last seen alive to being found dead was dichotomized in <1 hour or 1-24 hours. Clinical characteristics and autopsy results were compared, and predictors of autopsy were assessed by logistic regression. Of 440 unwitnessed SCD, 366 (83%) had not been seen alive within one hour of being found dead. Comorbidities differed between the groups with more epilepsy (17% vs 5%) and psychiatric diseases (13% vs 7%) in the 24-hour group. The 24-hour group died more frequently during sleep (64% vs 23%), the autopsy rate was higher (75% vs 61%), and deaths were more often unexplained after autopsy (69% vs 53%). Having been seen within one hour of death independently decreased the chance of being autopsied with OR 0.51 [95% CI 0.27-1.00, p = 0.0497]. The majority of unwitnessed SCD had not been seen alive within one hour of being found dead. Clinical- and autopsy-related characteristics differed among the two groups. Differences were mainly attributable to death-related circumstances and comorbidities. Excluding SCD cases not seen alive within one hour of being found dead would severely underestimate the burden of SCD.

High Rates of Illicit Drug Use Identified in Young Sudden Cardiac Death Patients

High Rates of Illicit Drug Use Identified in Young Sudden Cardiac Death Patients

"It's Overwhelming With the Grief" A Qualitative Study of Families' Experiences When a Young Relative Dies of Sudden Cardiac Death.

Sudden cardiac death (SCD) in younger individuals is frequently caused by heritable cardiac conditions. The unexpected nature of SCD leaves families with many unanswered questions and an insufficient understanding of the cause of death and their own risk for heritable disease. We explored the experiences of families of young SCD victims upon learning about their relative's cause of death and how they perceive their own risk for heritable cardiac conditions. We conducted a qualitative descriptive study, by interviewing families of young (ages 12-45) SCD victims, who died between 2014 and 2018 from a heritable cardiac condition and were investigated by the Office of the Chief Coroner of Ontario, Canada. We used thematic analysis to analyze the transcripts. Between 2018 and 2020, we interviewed 19 family members, of which 10 were males and 9 were females, ages ranging from 21 to 65 (average 46.2±13.1). Four main themes were revealed, each representing a distinct time period that families experience along a trajectory: (1) interactions between bereaved family and others, in particular coroners, shaped their search for answers about their relative's cause of death, with the types, formats, and timing of communication varying by case; (2) searching for answers and processing the cause of death; (3) incidental implications of the SCD event, such as financial strain and lifestyle changes contributed to cumulative stress; (4) receiving answers (or not) and moving forward. Families rely on communication with others, yet the type, formats, and timing of information received varies, which can influence families' experiences of processing the death (and its cause), their perceived risk and their decision to pursue cascade screening. These results may provide key insights for the interprofessional health care team responsible for the delivery and communication of the cause of death to families of SCD victims.

Sudden Cardiac Death in People With Schizophrenia: Higher Risk, Poorer Resuscitation Profiles, and Differing Pathologies

BackgroundPeople with schizophrenia account for approximately 1.0% of the population and seem to experience increased rates of sudden cardiac death (SCD). ObjectivesThis study sought to determine characteristics of increased SCD in people with schizophrenia. MethodsThe End Unexplained Cardiac Death (EndUCD) prospective state-wide registry compared people aged 15 to 50 years with and without schizophrenia who experienced SCD within a 2-year time period and were referred for forensic evaluation. ResultsWe identified 579 individuals, of whom 65 (11.2%) had schizophrenia. Patients with schizophrenia were more commonly smokers (46.2% vs 23.0%; P < 0.0001), consumed excess alcohol (32.3% vs 21.4%; P = 0.05), and used QTc-prolonging medications (69.2% vs 17.9%; P < 0.0001). They were less likely to arrest while exercising (0.0% vs 6.4%; P = 0.04). Unfavorable arrest-related factors included lower rates of witnessed arrest (6.2% vs 23.5%; P < 0.0001), more likely to be found in asystole (92.3% vs 73.3%; P < 0.0001), and being more likely to be found as part of a welfare check after a prolonged period of time (median 42 hours vs 12 hours; P = 0.003). There was more frequent evidence of decomposition, and they more commonly underwent autopsy (41.2% vs 26.4%; P = 0.04 and 93.8% vs 82.5%; P = 0.05), with a diagnosis of nonischemic cardiomyopathy being more common (29.2% vs 18.1%; P = 0.04). ConclusionsPeople with schizophrenia account for 11% of young SCD patients referred for forensic investigations, exceeding population rates by 11-fold. They have a higher preexisting cardiac risk factor burden, unfavorable resuscitation profiles, and higher rates of nonischemic cardiomyopathy. Strategies targeting biopsychosocial support may deliver not only psychological benefits, but also help to decrease unwitnessed cardiac arrest.

De Novo Asp219Val Mutation in Cardiac Tropomyosin Associated with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), caused by mutations in thin filament proteins, manifests as moderate cardiac hypertrophy and is associated with sudden cardiac death (SCD). We identified a new de novo variant, c.656A>T (p.D219V), in the TPM1 gene encoding cardiac tropomyosin 1.1 (Tpm) in a young SCD victim with post-mortem-diagnosed HCM. We produced recombinant D219V Tpm1.1 and studied its structural and functional properties using various biochemical and biophysical methods. The D219V mutation did not affect the Tpm affinity for F-actin but increased the thermal stability of the Tpm molecule and Tpm-F-actin complex. The D219V mutation significantly increased the Ca2+ sensitivity of the sliding velocity of thin filaments over cardiac myosin in an in vitro motility assay and impaired the inhibition of the filament sliding at low Ca2+ concentration. The molecular dynamics (MD) simulation provided insight into a possible molecular mechanism of the effect of the mutation that is most likely a cause of the weakening of the Tpm interaction with actin in the "closed" state and so makes it an easier transition to the “open” state. The changes in the Ca2+ regulation of the actin-myosin interaction characteristic of genetic HCM suggest that the mutation is likely pathogenic.

Obesity in young sudden cardiac death: rates, clinical features, and insights into people with body mass index &amp;gt;50kg/m2

Abstract Background Obesity is common in young sudden cardiac death (SCD) victims but it is unclear whether it is more common than in the general population. This study aimed to contextualize young SCD obesity rates, identifying clinical and pathologic features in WHO class II and III obesity. Methods A prospective state-wide out-of-hospital cardiac arrest registry included all SCDs in Victoria, Australia from 2019–2021. Body mass indices (BMIs) of patients 18–50 years were compared to age-referenced general population. Characteristics of SCD patients with WHO Class II obesity (BMI ≥30kg/m2) and non-obesity (BMI &amp;lt;30kg/m2) were compared. Clinical characteristics of people with BMI &amp;gt;50kg/m2 were assessed. Results 504 patients were included. Obesity was strongly over-represented in young SCD compared to the age-matched general population (55.0% vs 28.7%, p&amp;lt;0.0001). Obese SCD patients more frequently had hypertension, diabetes and obstructive sleep apnoea (p&amp;lt;0.0001, p=0.009 and p=0.001 respectively), ventricular fibrillation as their arrest rhythm (p=0.008) and left ventricular hypertrophy (LVH) (p&amp;lt;0.0001). Obese patients were less likely to have toxicology positive for illicit substances (22.0% vs 32.6%, p=0.008) or significant alcohol history (18.8% vs 26.9%, p=0.030). Patients with BMI &amp;gt;50 kg/m2 represented 8.5% of young SCD. LVH (n=26, 60.5%) was their predominant cause of death and only 10 (9.3%) patients died from coronary disease. Conclusion Over half of young Australian SCD patients are obese, with all obesity classes over-represented compared to the general population. Obese patients had more cardiac risk factors. Almost two thirds of patients with BMI&amp;gt;50 kg/m2 died with LVH, with fewer than 10% dying from coronary disease. Funding Acknowledgement Type of funding sources: None.

Prevalence of illicit drug use in young sudden cardiac death patients; an Australian prospective cohort study

Abstract Background Illicit drug use may accelerate coronary disease and cardiac hypertrophy or stimulate arrhythmias. Rates of illicit drug use in young sudden cardiac death (SCD) patients are uncertain. Purpose To identify rates of illicit drug use in young SCD patients in Australia. Methods A prospective multi-centre registry identified out of hospital cardiac arrest (OHCA) patients aged 1–50 years between April 2019 and April 2020. Clinical characteristics were compared between patients with and without illicit drug use (defined by toxicological results or reported regular use). Illicit drugs included stimulants such as amphetamine-type substances and cocaine, or non-stimulants such as heroin, cannabis and novel psychoactive substances (cathinones and synthetic cannabinoids). Results 770 OHCAs occurred, with 555 patients undergoing forensic assessment. 287 patients had confirmed cardiac cause of OHCA, with 274 undergoing toxicological assessment and 79 (28.8%) having positive toxicology for illicit drugs (n=60) or reported regular drug use (n=19). An additional 121 patients experienced non-cardiac SCD due to illicit drug toxicity, resulting in a total of 200 patients (36.0% of OHCAs) with illicit drug use. Patients with SCD and illicit drug use were more commonly male (86.1% vs 72.3%, p=0.015), regular smokers (36.7% vs 21.5%, p=0.009), had cardiomegaly (76.5% vs 57.5%, p=0.007), and higher rates of coronary disease and cardiomyopathy (coronary disease 44.3% vs 33.3%, cardiomyopathy 30.4% vs 18.5%, p=0.003). Methamphetamines (n=42, 53.1%) were the most common illicit drug identified and polysubstance abuse occurred frequently (n=15, 19.0%). Conclusion Approximately one-third of young SCD patients use illicit drugs, with high rates of polysubstance abuse. Illicit drug use in SCD patients is associated with coronary disease and cardiomyopathy. Funding Acknowledgement Type of funding sources: None.

Prevalence of coronary artery anomalies in young sudden cardiac death: insights from a prospective state-wide registry

Abstract Background Coronary artery anomalies (CAAs) have been previously implicated as a major cause of young sudden cardiac death (SCD), particularly in exercise-related SCD with a reported prevalence of up to 33%. Methods A state-wide prospective out-of-hospital cardiac arrest registry identified all patients aged 1–50 years who experienced an SCD and underwent autopsy from April 2019 to April 2021. Rates of normal anatomy, normal variants and CAAs were identified and circumstances and cause of death for patients with CAAs examined. Results Of 1,477 patients who experienced cardiac arrest during the study period, 490 underwent autopsy and were confirmed to have experienced SCD. Of these 490 patients, five (1.0%) had a CAA identified with three having anomalies of coronary origin and two having anomalies of coronary course. In no cases was the CAA deemed responsible for the SCD. In two cases, severe coronary disease and intra-coronary thrombus with histological evidence of acute myocardial infarction were identified, in the third critical coronary disease was found, the fourth had an unrelated thoracic aortic dissection and the fifth had cardiomegaly in the setting of illicit drug use. Of 27 patients who experienced their SCD during exercise, only one had a CAA identified (the patient with thoracic aortic dissection). Conclusion In this prospective cohort of consecutive young patients with SCD who underwent autopsy, CAAs occurred in 1.0% of patients and did not cause any deaths. The role of CAAs in causing young SCD appears to be less significant than previously hypothesised. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): NHMRC, NHF

Effect of time on characterics and cause of death in unwitnessed, young sudden cardiac death cases

Abstract Introduction Around 50% of all sudden cardiac death (SCD) cases are unwitnessed. According to the World Health Organization's definition of sudden cardiac death, any unwitnessed death is considered SCD if the person was last seen alive and well within 24 hours of death and with confirmed or suspected cardiac cause of death. The length of this timespan has been debated, as the nature of death in unwitnessed cases is less certain compared to witnessed cases. The effect of time on the composition of the group of unwitnessed SCD cases has not previously been assessed. Purpose This study aimed to compare clinical characteristics and causes of death among unwitnessed SCD cases last seen alive within 1 hour or 24 hours. Methods This nationwide, retrospective study conducted in Denmark included all deceased persons aged 1–35 from 2000–2014. The highly descriptive Danish death certificates were utilized to identify all sudden and unexpected deaths. Through subsequent examination of autopsy reports and discharge summaries, we identified all SCD cases. In addition, witnessed status and time since last seen alive (1 vs. 24 hours) were recorded. Information on comorbidities was collected from the Danish Health Registries. Results During the 15-year study period, we identified 857 SCD. Of these, 353 (41%) were witnessed, and 441 (51%) were unwitnessed; 62 (7%) cases had unknown witnessed status. Among the unwitnessed SCD, 75 (17%) were last seen alive within 1 hour, and the remaining 366 (83%) were seen alive within 24 hours. Comparison of clinical characteristics and cause of death revealed few but distinct differences. Cases seen within 1 hour were of male predominance (82% vs. 65%, p=0.005). The comorbidity burden was similar, except for epilepsy which was significantly more prevalent among the group last seen alive within 24 hours. Circumstances regarding death also differed among the groups: Cases seen alive within 1 hour were more often awake at the time of death (72% vs. 36%, p&amp;lt;0.001) when compared to cases seen alive within 24 hours, and they were less often autopsied (61% vs. 75%, p=0.02). Among autopsied cases, structural heart disease was more often the cause of death among persons last seen alive within 1 hour (58% vs. 40%, p=0.02). In both groups. The most common cause of death was sudden unexpected death, but the proportion was significantly higher in the 24-hour group (60% vs 42%, p=0.03). Arrhythmogenic cardiomyopathy and thoracic aortic dissection were significantly more prevalent among cases seen within 1 hour (11% vs. 3%, p=0.002 for both). Conclusions In this 15-year nationwide study of SCD in Denmark, we found few, marked differences in cause of death and clinical characteristics between unwitnessed SCD last seen alive within 1 and 24 hours. Male sex predominated in cases seen within 1 hour, and the autopsy rate was significantly lower. In the autopsied cases structural heart disease was more common in cases seen alive within 1 hour. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Copenhagen

Using codesign focus groups to develop an online COmmunity suPporting familiEs after Sudden Cardiac Death (COPE-SCD) in the young

ObjectiveTo codesign an online support intervention for families after sudden cardiac death (SCD) in the young (<35 years).DesignCodesign of an SCD family intervention by stakeholder focus groups.SettingFamilies and healthcare professionals...

Obesity in young sudden cardiac death: Rates, clinical features, and insights into people with body mass index >50kg/m2

ObjectiveTo contextualize obesity rates in young sudden cardiac death (SCD) against the age-matched national population, and identify clinical and pathologic features in WHO class II and III obesity. MethodsA prospective state-wide out-of-hospital cardiac arrest registry included all SCDs in Victoria, Australia from 2019–2021. Body mass indices (BMIs) of patients 18-50 years were compared to age-referenced general population. Characteristics of SCD patients with WHO Class II obesity (BMI ≥30kg/m2) and non-obesity (BMI<30kg/m2) were compared. Clinical characteristics of people with BMI>50kg/m2 were assessed. Results504 patients were included. Obesity was strongly over-represented in young SCD compared to the age-matched general population (55.0% vs 28.7%, p<0.0001). Obese SCD patients more frequently had hypertension, diabetes and obstructive sleep apnoea (p<0.0001, p=0.009 and p=0.001 respectively), ventricular fibrillation as their arrest rhythm (p=0.008) and left ventricular hypertrophy (LVH) (p<0.0001). Obese patients were less likely to have toxicology positive for illicit substances (22.0% vs 32.6%, p=0.008) or history of alcohol abuse (18.8% vs 26.9%, p=0.030). Patients with BMI>50 kg/m2 represented 8.5% of young SCD. LVH (n=26, 60.5%) was their predominant cause of death and only 10 (9.3%) patients died from coronary disease. ConclusionOver half of young Australian SCD patients are obese, with all obesity classes over-represented compared to the general population. Obese patients had more cardiac risk factors. Almost two thirds of patients with BMI>50 kg/m2 died from LVH, with fewer than 10% dying from coronary disease.

Lack of early etiologic investigations in young sudden cardiac death

BackgroundSince majority of sudden cardiac arrest (SCA) victims die in the intensive care unit (ICU), early etiologic investigations may improve understanding of SCA and targeted prevention. MethodsIn this prospective, population-based registry all SCA admitted alive across the 48 hospitals of the Paris area were enrolled. We investigated the extent of early etiologic work-up among young SCD cases (<45 years) eventually dying within the ICU. ResultsFrom May 2011 to May 2018, 4,314 SCA patients were admitted alive. Among them, 3,044 died in ICU, including 484 (15.9%) young patients. SCA etiology was established in 233 (48.1%) and remained unexplained in 251 (51.9%). Among unexplained (compared to explained) cases, coronary angiography (17.9 vs. 49.4%, P < 0.001), computed tomography scan (24.7 vs. 46.8%, P < 0.001) and trans-thoracic echocardiography (31.1 vs. 56.7%, P < 0.001) were less frequently performed. Only 22 (8.8%) patients with unexplained SCD underwent all three investigations. SCDs with unexplained status decreased significantly over the 7 years of the study period (from 62.9 to 35.2%, P = 0.005). While specialized TTE and CT scan performances have increased significantly, performance of early coronary angiography did not change. Autopsy, genetic analysis and family screening were performed in only 48 (9.9%), 5 (1.0%) and 14 cases (2.9%) respectively. ConclusionsMore than half of young SCD dying in ICU remained etiologically unexplained; this was associated with a lack of early investigations. Improving early diagnosis may enhance both SCA understanding and prevention, including for relatives. Failure to identify familial conditions may result in other preventable deaths within these families.

Predictors and outcomes of in-hospital referrals for forensic investigation after young sudden cardiac death.

Forensic investigations are recommended following sudden cardiac death (SCD) to determine cause of death and identify living relatives at potential risk. Not all young SCD patients are referred to coronial services. The purpose of this study was to identify referral rates, predictors, and outcomes of young SCD patients who die in-hospital following out-of-hospital cardiac arrest (OHCA). A prospective 2-year analysis of in-hospital deaths following OHCA in Victoria, Australia, was conducted using a statewide registry combining data from ambulance, hospital, and forensic resources. OHCA caused 26.3% of all deaths (n = 1301) in Victorians aged 1-50 years. Rates of prehospital and in-hospital referral to coronial services were 95.0% and 59.5%, respectively. Factors independently predicting in-hospital coronial referral were age <40 years, death in the emergency department, and rural status (odds ratios 4.07, 8.91, and 3.43, respectively). Establishing a diagnosis of coronary disease in-hospital substantially reduced odds of coronial referral (odds ratio 0.07). Of 107 SCD patients referred to the coroner from hospitals, 25 (23.3%) had illicit substances identified on toxicologic analysis. Eighty-one patients (75.7%) underwent autopsy, with cause of death determined in 65 cases (80.2%). Sixteen deaths (19.8%) remained unascertained after autopsy and ancillary investigations. More than one-fourth of young Victorian deaths result from OHCA. Approximately half of patients dying in-hospital following OHCA are referred to the coroner. Patients referred are younger, more likely to die in the emergency department, and reside rurally. Forensic assessment identifies high rates of illicit drug use in young SCD patients and provides a definitive cause of death for most patients.

Prevalence of Coronary Artery Anomalies in Young and Middle-Aged Sudden Cardiac Death Victims (from a Prospective State-Wide Registry)

Coronary artery anomalies (CAAs) have been previously implicated as a major cause of young sudden cardiac death (SCD), particularly in exercise-related SCD, with a prevalence of up to 33%. A state-wide prospective out-of-hospital cardiac arrest registry identified all patients aged 1 to 50years who experienced an SCD and underwent autopsy from April 2019 to April 2021. Rates of normal anatomy, normal variants, and CAAs were identified, and circumstances and causes of death for patients with CAAs examined. Of 1,477 patients who experienced cardiac arrest during the study period, 490 underwent autopsy and were confirmed to have experienced SCD. Of these 490 patients, 5 (1%) had a CAA identified, with 3 having anomalies of coronary origin and 2 having anomalies of coronary course. In no cases were the CAA deemed responsible for the SCD. In 2 cases, severe coronary disease and intra-coronary thrombus with histological evidence of acute myocardial infarction were identified. In the third, critical coronary disease was found, the fourth had an unrelated thoracic aortic dissection, and the fifth had cardiomegaly in the setting of illicit drug use. Of 27 patients who experienced their SCD during exercise, only 1 had a CAA identified (the patient with thoracic aortic dissection). In conclusion, in this prospective cohort of consecutive young patients with SCD who underwent autopsy, CAAs occurred in 1% of patients and did not cause any deaths. The role of CAAs in causing young and middle-aged SCD appears to be less significant than previously hypothesized.

Next-Generation Sequencing in Genetic Testing of Kazakhstani Sudden Cardiac Death Cases

<h3>Purpose</h3> The use of next-generation sequencing (NGS) enables a rapid analysis of many genes associated with sudden cardiac death (SCD). It is particularly useful in cases where traditional autopsy is negative or only shows non-diagnostic features, i.e., in sudden unexplained deaths (SUDs), which are often due to an underlying inherited arrhythmogenic cardiac disease. SCD most commonly occurs in patients with coronary heart disease, whereas inherited cardiomyopathies and primary electrical disorders prevail in younger SCD victims (up to 30% of all SCD in the young). The aim of the study was to elucidate the mutational spectrum in Kazakhstani SCD victims revealed by NGS of 96 genes associated with cardiac diseases and compare the diagnostic yield of postmortem genetic testing in (1) cases with structural findings of uncertain significance at autopsy to (2) cases with autopsy findings diagnostic of cardiomyopathy. <h3>Methods</h3> We screened 37 suspected SCD cases (<45 years) using the customized HaloPlex Target Enrichment System (Agilent) and NGS for 96 genes associated with inherited cardiac syndromes and cardiomyopathies. 27 cases had non-diagnostic structural cardiac abnormalities and 10 cases, diagnosed with a cardiomyopathy post-mortem. ACMG/AMP guidelines were applied for variant interpretation of clinical significance. <h3>Results</h3> 31 rare variants were identified in 17 (63%) of the deceased individuals with non-diagnostic structural cardiac abnormalities. Among them pathogenic variants in KCNQ1, KCNJ2, SCN5A, RYR2 genes were identified. The corresponding frequency in deceased individuals with cardiomyopathies was 35%. The most abundant mutations observed in MYBPC3, LAMA2, MYH6 and GAA. <h3>Conclusion</h3> Genetic screening revealed variants with likely functional effects at high rates, in 63% and 35% of the SCD cases with non-diagnostic and diagnostic cardiac abnormalities, respectively. Targeted NGS screening can support the forensic investigation and help the cardiologist's decision to offer counselling and clinical evaluation to relatives of young SCD victims. NGS has nonetheless brought new challenges to molecular autopsy, especially regarding the clinical interpretation of the large number of variants of unknown significance detected in each individual. Study was supported by a grant from the Ministry Education and Science, Republic of Kazakhstan (AP09563474).

Post-mortem genetic investigation in sudden cardiac death victims: complete exon sequencing of forty genes using next-generation sequencing.

Sudden cardiac death (SCD) in young people is predominantly caused by genetic causes as cardiomyopathies. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disease and is responsible for the major proportion of SCD in the young. The purpose of this study was to identify the genetic variants present in young SCD victims with HCM characteristics. From the Portuguese records of autopsies performed at the National Institute of Legal Medicine and Forensic Sciences, North Delegation, 16 young (16-50 years) SCD victims whose death was suspected to be a manifestation of HCM were selected. Using next-generation sequencing, the coding regions of 40 genes associated with HCM, candidates, or strongly related to HCM-phenocopies were investigated. The victims included in this study were all males, with a mean age of 33.4 ± 11.7 years, left ventricle mean thickness of 21.5 ± 6.28 mm, and the majority of deaths occurred during sleep (36%). A pathogenic or likely pathogenic variant was identified in six out of 16 (37.5%) victims, in the most common HCM genes (MYBPC3 and MYH7). Our results indicate that molecular autopsy of SCD victims contributes to a more precise identification of a cause of death, and this can be used in the prevention of SCD cases through family screening of first relatives who may carry the same pathogenic variant.

Predictors and Outcomes of In-Hospital Referrals for Forensic Investigation After Young Sudden Cardiac Death

Forensic investigations are recommended following sudden cardiac death (SCD) to determine cause of death and identify living relatives at potential risk. Not all young SCD patients are referred to coronial services.