Sudden Arrhythmic Death Syndrome Research Articles

Lack of genotype-phenotype correlation in Brugada Syndrome and Sudden Arrhythmic Death Syndrome families with reported pathogenic SCN1B variants

There is limited evidence that Brugada Syndrome (BrS) is due to SCN1B variants (BrS5). This gene may be inappropriately included in routine genetic testing panels for BrS or Sudden Arrhythmic Death Syndrome (SADS). We sought to characterize the genotype-phenotype correlation in families who had BrS and SADS with reportedly pathogenic SCN1B variants and to review their pathogenicity. Families with BrS and SADS were assessed from 6 inherited arrhythmia centers worldwide, and a comprehensive literature review was performed. Clinical characteristics including relevant history, electrocardiographic parameters and drug provocation testing results were studied. SCN1B genetic testing results were reclassified using American College of Medical Genetics criteria. A total of 23 SCN1B genotype-positive individuals were identified from 8 families. Four probands (17%) experienced ventricular fibrillation or sudden cardiac death at the time of presentation. All family members were free from syncope or ventricular arrhythmias. Only 2 of 23 genotype-positive individuals (9%) demonstrated a spontaneous BrS electrocardiographic pattern. Drug challenge testing for BrS in 87% (13 of 15) was negative. There was no difference in PR interval (161 ± 7 ms vs 165 ± 9 ms; P=.83), QRS duration (101 ± 6 ms vs 89 ± 5 ms; P = .35), or corrected QT interval (414 ± 35 ms vs 405 ± 8 ms; P = .7) between genotype-positive and genotype-negative family members. The overall frequency of previously implicated SCN1B variants in the Genome Aggregation Database browser is 0.004%, exceeding the estimated prevalence of BrS owing to SCN1B (0.0005%), including 15 of 23 individuals (65%) who had the p.Trp179X variant. The lack of genotype-phenotype concordance among families, combined with the high frequency of previously reported mutations in the Genome Aggregation Database browser, suggests that SCN1B is not a monogenic cause of BrS or SADS.

The Diagnostic Yield of Brugada Syndrome After Sudden Death With Normal Autopsy

BackgroundFamilial evaluation after a sudden death with negative autopsy (sudden arrhythmic death syndrome; SADS) may identify relatives at risk of fatal arrhythmias. ObjectivesThis study aimed to assess the impact of systematic ajmaline provocation testing using high right precordial leads (RPLs) on the diagnostic yield of Brugada syndrome (BrS) in a large cohort of SADS families. MethodsThree hundred three SADS families (911 relatives) underwent evaluation with resting electrocardiogram using conventional and high RPLs, echocardiography, exercise, and 24-h electrocardiogram monitor. An ajmaline test with conventional and high RPLs was undertaken in 670 (74%) relatives without a familial diagnosis after initial evaluation. Further investigations were guided by clinical suspicion. ResultsAn inherited cardiac disease was diagnosed in 128 (42%) families and 201 (22%) relatives. BrS was the most prevalent diagnosis (n = 85, 28% of families; n = 140, 15% of relatives). Ajmaline testing was required to unmask the BrS in 97% of diagnosed individuals. The use of high RPLs showed a 16% incremental diagnostic yield of ajmaline testing by diagnosing BrS in an additional 49 families. There were no differences of the characteristics between individuals and families with a diagnostic pattern in the conventional and the high RPLs. On follow-up, a spontaneous type 1 Brugada pattern and/or clinically significant arrhythmic events developed in 17% (n = 25) of the concealed BrS cohort. ConclusionsSystematic use of ajmaline testing with high RPLs increases substantially the yield of BrS in SADS families. Assessment should be performed in expert centers where patients are counseled appropriately for the potential implications of provocation testing.

Neurochemical Alterations in Sudden Unexplained Perinatal Deaths-A Review.

Sudden unexpected perinatal collapse is a major trauma for the parents of victims. Sudden infant death syndrome (SIDS) is unexpected and mysterious death of an apparently healthy neonate from birth till 1 year of age without any known causes, even after thorough postmortem investigations. However, the incidence of sudden intrauterine unexplained death syndrome (SIUDS) is seven times higher as compared with SIDS. This observation is approximated 40–80%. Stillbirth is defined as death of a fetus after 20th week of gestation or just before delivery at full term without a known reason. Pakistan has the highest burden of stillbirth in the world. This basis of SIDS, SIUDS, and stillbirths eludes specialists. The purpose of this study is to investigate factors behind failure in control of these unexplained deaths and how research may go ahead with improved prospects. Animal models and physiological data demonstrate that sleep, arousal, and cardiorespiratory malfunctioning are abnormal mechanisms in SIUDS risk factors or in newborn children who subsequently die from SIDS. This review focuses on insights in neuropathology and mechanisms of SIDS and SIUDS in terms of different receptors involved in this major perinatal demise. Several studies conducted in the past decade have confirmed neuropathological and neurochemical anomalies related to serotonin transporter, substance P, acetylcholine α7 nicotine receptors, etc., in sudden unexplained fetal and infant deaths. There is need to focus more on research in this area to unveil the major curtain to neuroprotection by underlying mechanisms leading to such deaths.

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.

Critical Roles of Xirp Proteins in Cardiac Conduction and Their Rare Variants Identified in Sudden Unexplained Nocturnal Death Syndrome and Brugada Syndrome in Chinese Han Population.

BackgroundSudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative entity with unclear etiology. Arrhythmia has been implicated in SUNDS. Mutations/deficiencies in intercalated disc components have been shown to cause arrhythmias. Human cardiomyopathy‐associated 1 (XIRP1) and 3 (XIRP2) are intercalated disc–associated, Xin repeats‐containing proteins. Mouse Xirp1 is necessary for the integrity of intercalated disc and for the surface expression of transient outward and delayed rectifier K+ channels, whereas mouse Xirp2 is required for Xirp1 intercalated disc localization. Thus, XIRP1 and XIRP2 may be potentially causal genes for SUNDS.Methods and ResultsWe genetically screened XIRP genes in 134 sporadic SUNDS victims and 22 Brugada syndrome (BrS) cases in a Chinese Han population. We identified 16 rare variants (6 were in silico predicted as deleterious) in SUNDS victims, including a novel variant, XIRP2‐E215K. There were also four rare variants (2 were in silico predicted as deleterious) detected in BrS cases, including a novel variant, XIRP2‐L2718P. Interestingly, among these 20 variants, we detected 2 likely pathogenic variants: a nonsense variant (XIRP2‐Q2875*) and a frameshift variant (XIRP2‐T2238QfsX7). Analyzing available Xirp2 knockout mice, we further found that mouse hearts without Xirp2 exhibited prolonged PR and QT intervals, slow conduction velocity, atrioventricular conduction block, and an abnormal infranodal ventricular conduction system. Whole‐cell patch‐clamp detected altered ionic currents in Xirp2 −/− cardiomyocytes, consistent with the observed association between Xirp2 and Nav1.5/Kv1.5 in co‐immunoprecipitation.ConclusionsThis is the first report identifying likely pathogenic XIRP rare variants in arrhythmogenic disorders such as SUNDS and Brugada syndrome, and showing critical roles of Xirp2 in cardiac conduction.

Editorial introductions

Editorial introductions

Risk Factors of Sudden Cardiac Death in the Young: Multiple-Year Community-Wide Assessment.

Prevention of sudden cardiac arrest (SCA) in the young remains a largely unsolved public health problem, and sports activity is an established trigger. Although the presence of standard cardiovascular risk factors in the young can link to future morbidity and mortality in adulthood, the potential contribution of these risk factors to SCA in the young has not been evaluated. We prospectively ascertained subjects who experienced SCA between the ages of 5 and 34 years in the Portland, Oregon, metropolitan area (2002-2015, catchment population ≈1 million). We assessed the circumstances, resuscitation outcomes, and clinical profile of subjects who had SCA by a detailed evaluation of emergency response records, lifetime clinical records, and autopsy examinations. We specifically evaluated the association of standard cardiovascular risk factors and SCA, and sports as a trigger for SCA in the young. Of 3775 SCAs in all age groups, 186 (5%) occurred in the young (mean age 25.9±6.8, 67% male). In SCA in the young, overall prevalence of warning signs before SCA was low (29%), and 26 (14%) were associated with sports as a trigger. The remainder (n=160) occurred in other settings categorized as nonsports. Sports-related SCAs accounted for 39% of SCAs in patients aged ≤18, 13% of SCAs in patients aged 19 to 25, and 7% of SCAs in patients aged 25 to 34. Sports-related SCA cases were more likely to present with shockable rhythms, and survival from cardiac arrest was 2.5-fold higher in sports-related versus nonsports SCA (28% versus 11%; P=0.05). Overall, the most common SCA-related conditions were sudden arrhythmic death syndrome (31%), coronary artery disease (22%), and hypertrophic cardiomyopathy (14%). There was an unexpectedly high overall prevalence of established cardiovascular risk factors (obesity, diabetes mellitus, hypertension, hyperlipidemia, smoking) with ≥1 risk factors in 58% of SCA cases. Sports was a trigger of SCA in a minority of cases, and, in most patients, SCA occurred without warning symptoms. Standard cardiovascular risk factors were found in over half of patients, suggesting the potential role of public health approaches that screen for cardiovascular risk factors at earlier ages.

Febrile seizures prior to sudden cardiac death: a Danish nationwide study

Febrile seizure (FS) is a common disorder affecting 2-5% of children up to 5years of age. The aim of this study was to determine whether FS in early childhood are over-represented in young adults dying from sudden cardiac death (SCD). We included all deaths (n = 4595) nationwide and through review of all death certificates, we identified 245 SCD in Danes aged 1-30 years in 2000-09. Through the usage of nationwide registries, we identified all persons admitted with first FS among SCD cases (14/245; 5.7%) and in the corresponding living Danish population (71027/2369785; 3.0%) and also in victims of transport accidents (26/917; 2.8%). The frequency of FS among SCD cases was significantly increased by an odds ratio of 1.96 [95% confidence interval (CI) 1.14-3.36; P = 0.021] compared with the living Danish population and with an odds ratio of 2.08 (95% CI 1.07-4.04; P = 0.046) compared with transport accident victims. SCD cases did not differ statistically in birth year (P = 0.272), age at SCD (P = 0.667) or prior medical conditions, except for epilepsy (P < 0.001), when comparing SCD with and without prior FS. The most common cause of death in autopsied SCD cases with FS was sudden arrhythmic death syndrome (5/8; 62.5%). In conclusion, this study demonstrates a significantly two-fold increase in the frequency of FS prior to death in young SCD cases compared with the two control groups, suggesting that FS could potentially contribute in a risk stratification model for SCD and warrant further studies.

Mitochondrial DNA content: A new biomarker for sudden intrauterine unexplained death syndrome (SIUDS)

In literature there are no data related to mitochondrial DNA (mtDNA) content in sudden intrauterine unexplained death syndrome (SIUDS). To test the hypothesis that a quantitative excess of mtDNA could play a role in the pathogenesis of SIUDS, mtDNA content was measured in cerebral cortex of 9 SIUDS and in 7 controls. The median (interquartile range) mtDNA in SIUDS and controls was 14,000 (8600–33,500), 3400 (0–8500) copies per nuclear DNA, respectively (p=0.007). If mitochondria are involved in SIUDS, then higher mitochondrial DNA content may be a biomarker of this syndrome.

Genetic Knowledge of Parents and Children With Inherited Cardiac Syndromes

Abstract Although genetic knowledge related to sudden arrhythmia death syndromes (SADS) has enhanced risk prediction and treatment, it is challenging to assess genetic literacy of individual patients and families. To address this, participants attending the 2015 SADS conference were asked to complete a survey measuring general knowledge of genes and heredity. Correct responses averaged 85 ± 9% with correct responses of ≥ 80% for 17 of 21 questions. However, attitudes toward genetic testing varied markedly. These results suggest that understanding motivations or disincentives to pursue genetic testing is as important as enhancing genetic knowledge for providing effective treatments for SADS.

P4933Comprehensive familial evaluation in Sudden Arrhythmic Death Syndrome (SADS) families leads to significant yields of Brugada syndrome (BrS)

P4933Comprehensive familial evaluation in Sudden Arrhythmic Death Syndrome (SADS) families leads to significant yields of Brugada syndrome (BrS)

The "Bare Life" of Thai Transnational Migrant Workers in Taiwan

In 2009, in an area of Taiwan distinguished by family-operated factories, a young Thai fell victim to sudden unexplained death syndrome. His Indonesian female lover may have been an indirect cause of his death, as her previous lover may have paid for the use of black magic against him. The victim's older brother originally wanted to seek revenge, but his ageing mother dissuaded him. The brother was, in turn, involved with an Indonesian woman in Taiwan, whose child by him he continued to support after her return home. This loyalty led his Taiwanese lover to stab him in his sleep. While he survived, these episodes serve to illustrate the lives and losses of Thai and other transnational migrant workers.

Molecular investigation by whole exome sequencing revealed a high proportion of pathogenic variants among Thai victims of sudden unexpected death syndrome.

IntroductionSudden unexpected death syndrome (SUDS) is an important cause of death in young healthy adults with a high incident rate in Southeast Asia; however, there are no molecular autopsy reports about these victims. We performed a combination of both a detailed autopsy and a molecular autopsy by whole exome sequencing (WES) to investigate the cause of SUDS in Thai sudden death victims.Materials and methodsA detailed forensic autopsy was performed to identify the cause of death, followed by a molecular autopsy, in 42 sudden death victims who died between January 2015 and August 2015. The coding sequences of 98 SUDS-related genes were sequenced using WES. Potentially causative variants were filtered based on the variant functions annotated in the dbNSFP database. Variants with inconclusive clinical significance evidence in ClinVar were resolved with a variant prediction algorithm, metaSVM, and the frequency data of the variants found in public databases, such as the 1000 Genome Project, ESP6500 project, and the Exome Aggregation Consortium (ExAc) project.ResultsCombining both autopsy and molecular autopsy enabled the potential identification of cause of death in 81% of the cases. Among the 25 victims with WES data, 72% (18/25) were found to have potentially causative SUDS mutations. The majority of the victims had at a mutation in the TTN gene (8/18 = 44%), and only one victim had an SCN5A mutation.ConclusionsWES can help to identify the genetic causes in victims of SUDS and may help to further guide investigations into their relatives to prevent additional SUDS victims.

Sudden unexplained death in alcohol misuse (SUDAM) patients have different characteristics to those who died from sudden arrhythmic death syndrome (SADS)

There is growing awareness of sudden unexplained death in alcohol misuse (SUDAM) in which there is no obvious cause of death, no evidence of acute alcohol toxicity or alcoholic ketoacidosis, and the heart is morphologically normal. This study describes the characteristics of a cohort with SUDAM from a tertiary cardiovascular referral center and compares the findings with those of individuals who died from sudden arrhythmic death syndrome (SADS). Cases in this retrospective cross-sectional study were identified from a database of referrals to our center spanning approximately 40 years. Cases with recorded heavy use of alcohol and non-alcohol users were selected, then limited to those with SUDAM or SADS aged 16 to 64 years. 62 cases of SUDAM and 41 cases of SADS were identified. The SUDAM group were older than the SADS group; mean age 35.8 years and 27.7 years respectively (P=0.0002). There was also a higher incidence of significant psychiatric illness in SUDAM (19.7%) than SADS (2.4%) cases. Post mortem liver examination was more likely to reveal heavy livers in SUDAM than SADS (2196.1g and 1572.4g respectively; P=0.0033) and more fatty liver change (24.2% and 2.4%). SUDAM tends to occur in individuals who are older and have heavier livers than those with SADS. Psychiatric illness is also more common. SADS, unlike SUDAM, is often associated with heritable channelopathies that may affect surviving family members. Therefore, differentiating between SUDAM and SADS identifies families likely to benefit from screening for these mutations, thus preventing further sudden arrhythmic deaths.

Etiological diagnoses of out-of-hospital cardiac arrest survivors admitted to the intensive care unit: Insights from a French registry

BackgroundRespective proportions of final etiologies are disparate in cohorts of cardiac arrest patients, depending on examined population and diagnostic algorithms. In particular, prevalence and characteristics of sudden unexplained death syndrome (SUDS) are debated. We aimed at describing etiologies in a large cohort of aborted out-of-hospital cardiac arrest (OHCA) patients, in order to assess prevalence and outcome of SUDS. Patients and methodsWe analyzed data from our prospective registry of successfully resuscitated OHCA patients admitted to a cardiac arrest centre between January 2002 and December 2014. The in-ICU diagnostic strategy included early coronary angiogram, brain and chest CT scan. This was completed by an extensive diagnostic strategy, encompassing biological and toxicological tests, repeated electrocardiograms and echocardiography, MRI and pharmacologic tests. Two independent investigators reviewed each final diagnosis. Baseline characteristics were compared between subgroups of patients. Three-month mortality was compared between subgroups using univariate Kaplan-Meier curves. ResultsOver the study period, 1657 patients were admitted to our unit after an aborted OHCA. The event was attributed to a non-cardiac and a cardiac cause in 478 (32.0%) and 978 (65.5%) patients, respectively. The main cause of cardiac related OHCA was ischemic heart disease (76.7%) while primary electrical diseases accounted for only 2.5%. Sudden unexplained deaths (SUDS) were observed in 37 (2.5%) patients. ConclusionWe observed that ischemic heart disease was by far the most common cause of cardiac arrest, while primary electrical diseases were much less frequent. SUDS accounted for a very small proportion of patients who suffered an aborted OHCA.

Brugada syndrome and the story of Dave

ABSTRACTBrugada syndrome (BrS) is a little known genetic condition that causes severe disturbances in cardiac rhythm and may result in sudden unexpected cardiac death in an apparently healthy person. The heart structure is typically normal but there are problems with electrical activity. The syndrome is named after Spanish brothers who are cardiologists, Pedro and Josep Brugada. BrS is the major cause of sudden unexplained death syndrome (SUDS), also known as sudden arrhythmic death syndrome (SADS). Following a description of the syndrome, including its prevalence and incidence, how it is diagnosed and how it can be treated, we consider those who survive a cardiac arrest and what problems they may face. Most publications focus on the medical aspects of BrS but, of course, cardiac arrest can result in hypoxic brain damage. We conclude with the story of Dave, a 25-year-old man diagnosed with BrS following a nose bleed and subsequent cardiac arrest. He was left with a visual impairment, dystonia, hypersensitivity, and language and cognitive dysfunction. We look at Dave’s strengths and weaknesses, his response to offered treatment, and his consequent improvement. We stress the contributions from members of the multidisciplinary team and offer suggestions for the rehabilitation of other survivors of BrS.

Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome

BackgroundSudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. ObjectivesThis study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. MethodsWe evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. ResultsA clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10-5). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. ConclusionsMolecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation.

An East Asian Common Variant Vinculin P.Asp841His Was Associated With Sudden Unexplained Nocturnal Death Syndrome in the Chinese Han Population.

BackgroundWe have identified the cardiomyopathy‐susceptibility gene vinculin (VCL) mutation M94I may account for a sudden unexplained nocturnal death syndrome (SUNDS) case. We addressed whether VCL common variant D841H is associated with SUNDS.Methods and ResultsIn 8 of 120 SUNDS cases, we detected an East Asian common VCL variant p.Asp841His (D841H). Comparing the H841 allele frequency of the general population in the local database (15 of 1818) with SUNDS victims (10 of 240) gives an odds ratio for SUNDS of 5.226 (95% CI, 2.321, 11.769). The VCL‐D841H variant was engineered and either coexpressed with cardiac sodium channel (SCN5A) in HEK293 cells or overexpressed in human induced pluripotent stem‐cell–derived cardiomyocytes to examine its effects on sodium channel function using the whole‐cell patch‐clamp method. In HEK293 cells, under physiological pH conditions (pH 7.4), D841H caused a 29% decrease in peak IN a amplitude compared to wild type (WT), whereas under acidotic conditions (pH 7.0), D841H decreased further to 43% along with significant negative shift in inactivation compared to WT at pH 7.4. In induced pluripotent stem‐cell‐derived cardiomyocytes, similar effects of D841H on IN a were observed. VCL colocalized with SCN5A at the intercalated disk in human cardiomyocytes. VCL was also confirmed to directly interact with SCN5A, and VCL‐D841H did not disrupt the association of VCL and SCN5A.ConclusionsA VCL common variant was genetically and biophysically associated with Chinese SUNDS. The aggravation of loss of function of SCN5A caused by VCL‐D841H under acidosis supports that nocturnal sleep respiratory disorders with acidosis may play a key role in the pathogenesis of SUNDS.

Sudden Cardiac Death: Pharmacotherapy and Proarrhythmic Drugs: A Nationwide Cohort Study in Denmark.

This study sought to describe the use of pharmacotherapy in a nationwide cohort of young patients withsudden cardiac death (SCD). Several drugs have been associated with an increased risk of SCD and sudden arrhythmic death syndrome (SADS). It remains unclear how pharmacotherapy may contribute to the overall burden of SCD in the generalpopulation. This was a nationwide study that included all deaths that occurred between 2000 and 2009 and between 2007 and 2009 in people age 1 to 35 years and 36 to 49 years, respectively. Two physicians identified all SCDs throughreview of death certificates. Autopsy reports were collected. Pharmacotherapy prescribed within 90 days before SCD was identified in the Danish Registry of Medicinal Product Statistics. We identified 1,363 SCDs; median age was 38 years (interquartile range: 29 to 45 years), and 72% (n= 975) were men. Autopsy was performed in 55%. Overall, 58% of SCD cases (n= 786) received at least 1 drug within 90 days before death. The most common drugs were analgesic drugs (n= 239; 18%), antihypertensive drugs (n= 234; 17%), andantibiotic drugs (n= 218; 16%). After multivariable adjustment, prescription of "brugadogenic" drugs or >1 QT-prolonging drug was associated with an increased risk of SADS compared with explained SCD (odds ratio: 2.16 [95%confidence interval: 1.12 to 4.17] and 2.91 [95% confidence interval: 1.46 to 5.81], respectively). Pharmacotherapy was identified in 58% of the SCD cases. After multivariable adjustment, there wasa2- and 3-fold increased risk of SADS compared with explained SCD in patients receiving brugadogenic drugs or>1QT-prolonging drug, respectively. Identification of high-risk patients is warranted to lower the burden of SCD.

Cardiovascular causes of maternal sudden death. Sudden arrhythmic death syndrome is leading cause in UK

ObjectiveThis study aims to determine the causes of sudden cardiac death during pregnancy and in the postpartum period and patients’ characteristics. There are few studies in the literature. MethodsEighty cases of sudden unexpected death due to cardiac causes in relation to pregnancy and postpartum period in a database of 4678 patients were found and examined macroscopically and microscopically. ResultsThe mean age was 30±7 years with a range from 16 to 43 years. About 30% were 35 years old or older; 50% of deaths occurred during pregnancy and 50% during the postpartum period. About 59.18% were obese or overweight where body mass index data were available. The leading causes of death were sudden arrhythmic death syndrome (SADS) (53.75%) and cardiomyopathies (13.80%). Other causes include dissection of aorta or its branches (8.75%), congenital heart disease (2.50%) and valvular disease (3.75%). ConclusionThis study highlights sudden cardiac death in pregnancy or in the postpartum period, which is mainly due to SADS with underlying channelopathies and cardiomyopathy. We wish to raise awareness of these frequently under-recognised entities in maternal deaths and the need of cardiological screening of the family as a result of the diagnosis.