Burden Of Sudden Cardiac Death Research Articles

Nationwide burden of sudden cardiac death among patients with a psychiatric disorder

BackgroundPatients with psychiatric disorders have increased all-cause mortality compared with the general population. Previous research has shown that there is a fourfold increased risk of sudden cardiac death (SCD) among...

A Rare Noncoding Enhancer Variant in SCN5A Contributes to the High Prevalence of Brugada Syndrome in Thailand.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder that causes sudden death in young adults. Rare genetic variants in the SCN5A gene encoding the Nav1.5 sodium channel and common noncoding variants at this locus are robustly associated with the condition. BrS is particularly prevalent in Southeast Asia but the underlying ancestry-specific factors remain largely unknown. Genome sequencing of BrS probands and population-matched controls from Thailand was performed to identify rare noncoding variants at the SCN5A-SCN10A locus that were enriched in patients with BrS. A likely causal variant was prioritized by computational methods and introduced into human induced pluripotent stem cell (hiPSC) lines using CRISPR-Cas9. The effect of the variant on SCN5A expression and Nav1.5 sodium channel current was then assessed in hiPSC-derived cardiomyocytes (hiPSC-CMs). A rare noncoding variant in an SCN5A intronic enhancer region was highly enriched in patients with BrS (detected in 3.9% of cases with a case-control odds ratio of 45.2). The variant affects a nucleotide conserved across all mammalian species and predicted to disrupt a Mef2 transcription factor binding site. Heterozygous introduction of the enhancer variant in hiPSC-CMs caused significantly reduced SCN5A expression from the variant-containing allele and a 30% reduction in Nav1.5-mediated sodium current density compared with isogenic controls, confirming its pathogenicity. Patients with the variant had severe phenotypes, with 89% experiencing cardiac arrest. This is the first example of a functionally validated rare noncoding variant at the SCN5A locus and highlights how genome sequencing in understudied populations can identify novel disease mechanisms. The variant partly explains the increased prevalence of BrS in this region and enables the identification of at-risk variant carriers to reduce the burden of sudden cardiac death in Thailand.

Nationwide burden of sudden cardiac death among patients with a psychiatric disorder

Abstract Background and aim Patients with psychiatric disorders have increased all-cause mortality compared to the general population. Previous research has shown that they have a 4-fold increased risk of sudden cardiac death (SCD) among the young. However, the risk across all age groups remains unknown. Purpose To investigate the incidence of SCD in patients with psychiatric disorders aged 18-90 years in the Danish population by systematically reviewing all deaths in one year. Methods We examined all deaths in Denmark among residents aged 18-90 years in 2010 by reviewing death certificates and autopsy reports. All deaths were categorized as non-SCD, or SCD, based on the available information. Psychiatric disorder was defined according to ICD-10 criteria, or by redemption of a prescription for psychotropic medication within one year prior to death. Results Out of 4.3 million residents in 2010 aged 18-90 years, we observed 45 703 deaths of which 6 002 were SCD. Overall, the incidence of SCD was 4.35 times (CI: 4.20-4.50, p-value <0.001) higher among patients with psychiatric disorders than in the general population and was age dependent (p-value <0.001). When adjusting for age, sex, and comorbidities, psychiatric disorders were independently associated with SCD, with a hazard ratio (HR) of 2.46 (2.33-2.60, p-value: <0.001), with highest SCD risk among patients suffering from schizophrenic disorders with a HR of 5.27 (4.23-6.56 p-value <0.001). Furthermore, patients with psychiatric disorders had an expected 10-year excess loss of life of which 13% was caused by SCD. Conclusion The rate of SCD in patients with psychiatric disorders was 4 times higher than in the general population. Having a psychiatric disorder is independently associated with SCD. Life-expectancy for an 18-year-old with a psychiatric disorder is projected to be 10-years shorter in comparison.Incidence rate of SCD by age groupExcess loss of life-years

Racial and Ethnic Disparities in Implantable Cardioverter-Defibrillator Utilization: A Contemporary Review.

Sudden cardiac arrest is associated with high morbidity and mortality. Despite having a disproportionate burden of sudden cardiac death (SCD), rates of primary and secondary prevention of SCD with implantable cardioverter-defibrillator (ICD) therapy are lower among eligible racially minoritized patients. This review highlights the racial and ethnic disparities in ICD utilization, associated barriers to ICD care, and proposed interventions to improve equitable ICD uptake. Racially minoritized populations are disproportionately eligible for ICD therapy but are less likely to see cardiac specialists, be counseled on ICD therapy, and ultimately undergo ICD implantation, fueling disparate outcomes. Racial disparities in ICD utilization are multifactorial, with contributions at the patient, provider, health system, and structural/societal level. Racial and ethnic disparities have been demonstrated in preventing SCD with ICD use. Proposed strategies to mitigate these disparities must prioritize care delivery and access to care for racially minoritized patients, increase the diversification of clinical and implementation trial participants and the healthcare workforce, and center reparative justice frameworks to rectify a long history of racial injustice.

The Impact of Heart Attack and Sudden Cardiac Death Risk Perception on Lifestyle Modification Intention Among Adults in Jazan Province.

This study aimed to assess the perception of sudden cardiac death (SCD) and heart attack risk and its influence on the intention to adopt healthy lifestyle behaviors among the general population in Jazan province, Saudi Arabia. SCD refers to an abrupt and unexpected loss of heart function resulting in death, and its incidence has been alarmingly increasing worldwide. Several factors, including smoking, hypertension, diabetes, obesity, and specific medications, have been associated with an elevated risk of SCD. A descriptive cross-sectional study was conducted using a pretested questionnaire distributed among the general population in Jazan province. Descriptive statistics, chi-square, and t-tests were employed for data analysis. The study included 974 participants with a mean age of 27.90 ± 9.32 years, of whom 56% were female. More than half of the participants perceived themselves as highly susceptible to SCD, and all participants demonstrated a moderate willingness and readiness to modify their unhealthy lifestyle behaviors. Age, gender, marital status, body mass index (BMI), history of hypertension, dyslipidemia, medication use, physical exercise, and family history of chronic diseases and SCD were statistically associated with the perception of SCD. The study revealed a high-risk perception and a moderate readiness to adopt lifestyle modifications. These findings can inform the development of effective strategies and support programs aimed at reducing the burden of SCD.

Temporal trends in baseline characteristics of implantable cardioverter defibrillator recipients for primary prevention of sudden cardiac death- The DAIPP program

Abstract Introduction Since expanding the indication for implantable cardioverter defibrillators (ICD) to primary prevention, the patient population of ICD carriers continues to evolve over time. In pursuit of progressively decreasing the burden of sudden cardiac death, improved patient selection and risk-benefit assessment demand, among others, awareness of these temporal changes in clinical baseline characteristics of the ICD population. Purpose The aim was to explore the temporal differences in baseline characteristics of ICD recipients implanted for primary prevention of sudden cardiac death (SCD), and perioperative complications, to improve understanding of ICD population selection over the last two decades in a real-world setting. Methods The Primary Prevention ICD French Registry (DAI-PP program) was initiated in 2002 with an overall aim to assess the risk-benefit ratio of the introduction of ICD for primary prevention over a 20-year period, including a pilot evaluation that finished in 2012. The pilot study laid ground for the ongoing prospective DAIPP Consortium that started in 2018 and is aiming to follow 10000 patients under remote monitoring, using a specific integrational research platform. The two cohorts are in this study compared with regards to baseline characteristics as well as perioperative outcomes, i.e., early mortality and procedural complications. Results This study included 8432 participants, 5521 from the pilot study and 2211 from the prospective trial, with a median follow up of 2.36 (IQR 1.25-3.75) years. Median age was 64 (IQR 56-71) years, 17% female and 61% had ischemic heart disease. Baseline characteristics that remained stable over time were age, cancer burden. Compared to the 2002-2012 period, recent findings found a significant increase in the proportion of females (15 vs 20%, p <0.001), pauci-symptomatic patients (New York Heart Association Functional class-NYHA II, 41 vs. 57%, p <0.001), narrow QRS patients (31 vs. 43%, p<0.001), use of subcutaneous ICD (0 vs. 14%, P<0.001) and more comorbidities including an increase in diabetes, and slight increase in stroke. Regarding pharmacological treatment, there was an increase in use of 2 or 3 medications (2: 6.5% to 16% p<0.001; 3: 20% to 33%, p<0.001) where more received beta blockers and amiodarone in the contemporary study. Perioperative complications decreased over time (13% to 7.9% p<0.001) with a decrease in early reinterventions (1.3% to 0.1% p<0.001) and discrete fall in number of infections (0.7% to 0.1%, p<0.001) and pocket hematoma (4.4% to 3.0% p<0.001). A slight upward trend in number of lead dislodgements was seen over time (1.3% to 1.7% p<0.001). See Table 1 for perioperative complications. Conclusion The primary prevention ICD population has significantly changed over time. An increase in women, comorbidities, and use of 2-3 medications was seen, coupled with more participants receiving a subcutaneous ICD. Perioperative complications decreased over time.

Assessing the benefit of a replacement implantable cardioverter-defibrillator device for primary prevention of sudden cardiac death

Abstract Background Implantable cardioverter-defibrillators (ICDs) have been shown to reduce the burden of sudden cardiac death in at-risk populations. However, data reflecting contemporary device programming and medication would be valuable, particularly when evaluating patients for a replacement ICD when they did not receive therapy from their original device. Purpose This real-world analysis examined the incidence of ICD therapy after routine generator replacement due to battery depletion in patients who didn’t receive therapy from their first ICD. Methods Data were obtained from a query of a deidentified database from 2007 to present. The final analysis included patients that underwent a generator replacement after 2012 due to battery depletion and who had received no therapy from their first ICD. Patients were divided into two groups based on their ICD indication status (primary prevention [PP] or secondary prevention [SP]). The main endpoint was time to first appropriate shock therapy, antitachycardia pacing (ATP) therapy, or any therapy (ATP or shock) after ICD replacement. Time to first therapy was plotted using the Kaplan-Meier method. Appropriateness of therapy was modeled via LASSO regression using characteristics present in both our dataset and the adjudicated PainFree SST trial. The model was fit on episodes from 80% of PainFree SST patients and validated on the remaining 20% before applying it to our dataset. Results A total of 8,383 patients were identified who met the criteria outlined above. Of these patients, 7,299 (66.3 ± 12.6 years old; 30.3% female) had a PP indication for an ICD and 1,084 (64.2 ± 14.0 years old; 30.3% female) had an SP indication. The mean longevity of initial ICD implants before replacement was similar in PP and SP patients (91.4 ± 16.2 vs 90.9 ± 16.3 months). At 7 years post-replacement, the incidence of first shock, ATP, or any therapy received by PP patients who did not receive first-device therapy was 16%, 23% and 27% respectively. After applying the model to estimate appropriateness of therapy, the appropriate therapy rates were 14%, 22%, and 26%, respectively (Figure 1). Similarly, SP patients who received no first-device therapy had an incidence of modeled first appropriate shock, ATP, and any therapy 7 years after ICD replacement of 12%, 20%, and 25%, respectively. The modeled 7-year inappropriate shock rate post-replacement was 4% in all patients. Conclusion In this large, long-term, real-world evaluation of ICD PP patients who hadn’t experienced a treated event with their initial device, 1 in 4 eventually received appropriate therapy from their second device. The results suggest that the underlying risk persists in these patients and device replacement may be necessary to protect them from experiencing a deadly event.

Do co-morbidities, frailty and functional status identify patients who may not benefit from ICD therapy?

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boston Scientific ISR lite. Background In carefully selected patients, Implantable Cardioverter Defibrillators reduce all-cause mortality by reducing the burden of sudden cardiac death. Most patients who have an ICD implant do not receive life-prolonging therapy from it. Little research has been undertaken to determine which patients benefit the least from ICD therapy. As patients age and accumulate comorbidities, the risk of death increases and the benefit of ICDs diminishes. Purpose We sought to evaluate the impact of comorbidity, frailty, functional status on death prior to ICD therapy as this group has the least to gain from ICD therapy. Methods A prospective, multicentre, observational study involving 15 English hospitals was undertaken. Patients were eligible for inclusion for the study if they were scheduled to have a de novo, replacement or an upgrade to a high-energy device (transvenous or subcutaneous ICD or CRT-D). Baseline characteristics were collected including age, gender, device type, LV function, medication, baseline bloods if available and were asked to complete a frailty assessment, Fried score; a functional status questionnaire (EQ5D5L), Charlson Co-morbidity Score and EQ5D5L data were calculated. Results In total, 662 patients were enrolled, mean age 65.6 (IQR 65-75) years, 77.3% male, 55.9% de novo implants, 33.4% replacements and 10.5% upgrade. Overall, 32% were for a secondary prevention indication, 49.% had a single or dual chamber transvenous ICD, 45.3% had a CRT-D and 5% had an S-ICD) implanted. A total of 63 patients (9.5%) died across this period, of these, 54 died without receiving appropriate therapy. Frailty was present in 83/662 (12.5%) and severe co-morbidity was present in 69/662 (10.4%). The overall survival probability estimated to be 90.2% at 2.5 years, and was 68% in frail patients. Figure 1. Multivariate predictors of death with no appropriate therapy were identified and a risk score comprising frailty, severe co-morbidity, age >70 years, eGFR <60 ml/min/1.73 m2 EQ5D5L <0.6 was developed. Table 1. The model performance was: sensitivity= 80.7%; specificity = 81.6%; precision 27.3%; accuracy 81.6% and AUC 0.81. Conclusion Frailty and severe co-morbidity are powerful, independent predictors of death with no appropriate in ICD/CRT-D recipients.

Exercise and the Heart: Benefits, Risks and Adverse Effects of Exercise Training.

Exercise has multiple health benefits and reduces cardiovascular morbidity and mortality. Regular exercise decreases the burden of cardiovascular risk factors and improves prognosis in several cardiac conditions. Despite these premises, sudden cardiac death (SCD) during sports may occur in apparently healthy athletes who perform at the highest levels. Accurate identification and prompt treatment of individuals at risk may reduce the burden of SCD. A possible cardiotoxic effect of intense exercise has been recently postulated, however this is still matter of controversy as causal relationships are often difficult to establish taking into account multiple confounders. Exercise is safe for the majority, even with cardiovascular disease. In this review, we focus on exercise and sports, discussing their benefits and risks and exercise recommendations for healthy individuals and those with cardiovascular disease.

Burden of sudden cardiac death in persons aged 1-40 years in the Czech Republic.

The aim of the study was to ascertain the incidence, circumstances and causes of sudden cardiac death in persons aged 1-40 years in the Czech Republic. De-identified autopsy reports of all individuals who died suddenly between the ages of 1-40 years during the period 2014-2019 inclusive in a selected area of the Czech Republic were analysed retrospectively. Persons with substantial cardiovascular pathology defined by histopathological criteria and those with a negative autopsy were included in the study. The latter were designated as sudden arrhythmic death syndrome. In total, 245 sudden cardiac death cases were identified resulting in an incidence rate of 2.4/100,000 person-years. Among the deceased, we found an enormous gender gap with men representing 81% of cases. More than 80% of deaths occurred during everyday activities or sleep, whereas only 7% were sports-related. The most common cause of death was coronary artery disease detected in 38%, which was followed by cardiomyopathies in 15%, sudden arrhythmic death syndrome in 12%, left ventricular hypertrophy in 10%, and congenital heart defects in 7%. Coronary artery disease is the predominant cause of sudden cardiac death in the young population of the Czech Republic. Hence, effective preventive measures targeted at the reduction of risk factors associated with early coronary artery disease should be reinforced. The second most prevalent cause in our population are potentially heritable heart conditions such as cardiomyopathies and sudden arrhythmic death syndrome. This fact has already prompted the introduction of molecular autopsy and cardiogenetic care for relatives in the Czech Republic.

Incidence and predictors of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy: a pooled analysis.

AimsArrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart muscle abnormality, is a major cause of sudden cardiac death (SCD). However, the burden of SCD and risk factors in ARVC are not clearly described. Thus, we estimated the rates and predictors of SCD in ARVC in a meta-analysis.Methods and resultsPubMed, Embase, and Web of Science were searched through 7 April 2021. Prospective studies reporting SCD from ARVC cohorts were included. Data were independently extracted by two reviewers and pooled in a random-effects meta-analysis. Fifty-two studies (n = 5485 patients) with moderate-to-low risk of bias were included. The pooled annualized rates of SCD were 0.65 per 1000 [95% confidence interval 0.00–6.43, I2 0.00%] in those with an implantable cardioverter-defibrillator (ICD) and 7.21 (2.38–13.79, I2 0.0%) in non-ICD cohorts: 7.14 in probands and 8.44 for 2010 Task Force Criteria (TFC). Multivariable predictors of life-threatening arrhythmic events including SCD were: age at presentation [adjusted hazard ratio 0.98 (0.97–0.99)], male sex [2.08 (1.29–3.36)], right ventricular (RV) dysfunction [6.99 (2.17–22.49)], QRS fragmentation [6.55 (3.33–12.90)], T-wave inversion [1.12 (1.02–1.24)], syncope at presentation [2.83 (2.40–4.08)], previous non-sustained ventricular tachyarrhythmia [2.53 (1.44–4.45)], and the TFC score [1.96 (1.02–3.76)], (P < 0.05). Predictors of appropriate ICD therapy were RV dysfunction, syncope, and inducible ventricular arrhythmia (P < 0.01).ConclusionThis meta-analysis demonstrates a high burden of SCD in ARVC patients, especially among probands and ARVC defined by the modified TFC. Better strategies are required to improve patient management and prevent SCD in ARVC. PROSPERO ID: CRD42020211761.

Harmonization of the definition of sudden cardiac death in longitudinal cohorts of the European Sudden Cardiac Arrest network – towards Prevention, Education, and New Effective Treatments (ESCAPE-NET) consortium

The burden of sudden cardiac death (SCD) in the general population is substantial and SCD frequently occurs among people with few or no known risk factors for cardiac disease. Reported incidences of SCD vary due to differences in definitions and methodology between cohorts. This study aimed to develop a method for adjudicating SCD cases in research settings and to describe uniform case definitions of SCD in an international consortium harmonizing multiple longitudinal study cohorts. The harmonized SCD definitions include both case definitions using data from multiple sources (eg, autopsy reports, medical history, eyewitnesses) as well as a method using only information from registers (eg, cause of death registers, ICD-10 codes). Validation of the register-based method was done within the consortium using the multiple sources definition as gold standard and presenting sensitivity, specificity, accuracy and positive predictive value. Consensus definitions of "definite," "possible" and "probable" SCD for longitudinal study cohorts were reached. The definitions are based on a stratified approach to reflect the level of certainty of diagnosis and degree of information. The definitions can be applied to both multisource and register-based methods. Validation of the method using register-information in a cohort comprising 1335 cases yielded a sensitivity of 74%, specificity of 88%, accuracy of 86%, and positive predictive value of 54%. This study demonstrated that a harmonization of SCD classification across different methodological approaches is feasible. The developed classification can be used to study SCD in longitudinal cohorts and to merge cohorts with different levels of information.

A novel research platform for sudden cardiac death based on continuous, real-life, unlimited follow-up of a cohort of high-risk patients

Abstract Background/Introduction Currently, Sudden Cardiac Death (SCD) prevention is mainly based on implantable cardioverter-defibrillator (ICD) implantation in high risk patients. Real-time, prospective follow-up of such high-risk patients can afford a unique opportunity to improve SCD prevention. We previously conducted an exploratory retrospective project (DAIPP pilot program) focusing on &amp;gt;5 000 ICD recipients, which provided us with valuable information and knowledge to set up a wider, prospective project (1–11). Purpose We present here the organizational outline for an innovative research platform for SCD, based on a real-life cohort with continuous, unlimited follow-up. The overall aim is to garner high-value information which can help optimize individualized risk stratification, cardiac defibrillation, and preventive strategies to eventually decrease SCD burden. Methods and results The DAIPP Consortium is an investigator-initiated, prospective, multicentre, independent, long-term, academic cohort study, focusing on patients at high risk of SCD and implanted with an ICD. More than 5 000 ICD recipients will be enrolled prospectively and consecutively through 17 French tertiary public and private hospitals during the first three years. All patients will be monitored continuously through a unique remote monitoring platform, and they will be linked to the national “Health Data Hub”, gathering information about medications, hospitalizations and outcomes. Quality and exhaustivity of the collected data will be regularly monitored through systematic monthly automatic indices in each center. Events will be centrally adjudicated. For the 2021–2023 period, 6 work-packages have already been created within the research platform, some being clinical and others translational research, including ischemic cardiomyopathy, new technologies, congenital cardiomyopathies, channelopathies, complications and artificial intelligence, to develop new approaches. Concomitantly, the consortium will be open to external collaborations, and an academic research program has been initiated with various European universities to enable Master, PhD and Post-doctoral students to conduct their research on SCD. Conclusion DAIPP is an investigator-initiated real-life continuous follow-up cohort of patients at high risk of SCD. This project will provide an open research platform to enhance the understanding of, and improve preventive strategies for SCD. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Inserm, Société Française de Cardiologie, Clinique Pasteur

Nationwide burden of sudden cardiac death: A study of 54,028 deaths in Denmark.

A large proportion of all deaths are sudden cardiac deaths (SCDs). Reliable estimates of nationwide incidence of SCD, however, are missing. The goals of this study were to estimate SCD burden across all age groups in Denmark and to compare it with the estimates of other common causes of death. All deaths in Denmark (population of 5.5 million) in 2010 were manually reviewed case by case. Autopsy reports, death certificates, and information from nationwide health registries were systematically examined to identify all SCD cases in 2010. According to the level of detail of the available information, all deaths were categorized as either non-SCD, definite SCD, probable SCD, or possible SCD. There were 54,028 deaths in Denmark in 2010, of which 6867 (13%) were categorized as SCD (591 (9%) definite SCD, 1568 (23%) probable SCD, and 4708 (68%) possible SCD). The incidence rate of definite SCD was 11 (95% confidence interval 10-12) per 100,000 person-years. Including definite, probable, and possible SCD cases, the highest possible overall SCD incidence rate was 124 (95% confidence interval 121-127) per 100,000 person-years. Estimated SCD burden was similar to or greater than the estimates of all other common causes of death. Of all SCD cases, 49% were not diagnosed with cardiovascular disease before death. SCD accounted for up to 13% of all deaths. Almost half of all SCD cases occurred in persons without a history of cardiovascular disease. Consequently, the optimization of risk stratification and prevention of SCD in the general population should be given high priority.

Sudden cardiac death in athletes

Exercise is generally a good thing. However, for some it holds hidden danger. The following review discusses the incidence and aetiology of sudden cardiac death (SCD) and measures to reduce the burden of SCD.

4250Sports-related sudden cardiac arrest in Germany

Abstract Background Knowledge about causes of sports-related sudden cardiac arrest (SrSCA) may influence national strategies to prevent such events. Purpose We established a prospective registry on SrSCA to estimate the incidence and in particular describe the etiologies of SrSCA in the general population in Germany. Methods The registration of SrSCA based upon 4 pillars: a) a web-based platform to record SrSCA cases in competitive and recreational athletes, b) media-monitoring and c) a cooperation with the German Resuscitation Registry as well as d) 15 institutes of forensic medicine. Results After an observation period of 6 years, a total of 349 cases was recorded (mean age 48.0±12.7 years) of which 109 subjects survived. Most of the cases occurred during non-elite competitive or recreational sports. Bystander cardiopulmonary resuscitation (CPR) was initiated in 262 cases (75%), however rhythm analysis and defibrillation (if indicated) was mainly performed by medical service. In subjects ≤35 years, premature coronary artery disease (CAD) and sudden arrhythmic death syndrome (SADS) prevailed, followed by myocarditis. In athletes ≥35 years, CAD predominated. Conclusion The prevalence of cardiac pathologies in young athletes seems to vary across different countries. CAD represents the most common cause of SrSCA in the general population of Germany, highlighting the need for a targeted cardiovascular risk evaluation including young athletes. Public education on basic life support including the appropriate use of an automated external defibrillator (AED) may further decrease the burden of sudden cardiac death. Acknowledgement/Funding Funding from the German Heart Foundation

Sudden cardiac death caused by myocarditis in persons aged 1–49 years: a nationwide study of 14 294 deaths in Denmark

Myocarditis is associated with an increased risk of sudden cardiac death (SCD) in the young. However, information on nationwide burden of SCD caused by myocarditis (SCD-myocarditis) is sparse. For this study all deaths among persons in Denmark aged 1–35 years in 2000–2009 and 36–49 years in 2007–2009 (27.1 million person-years) were included. Autopsy reports, death certificates, discharge summaries, and nationwide registries were used to identify all cases of SCD-myocarditis. In the 10-year study period, there were 14 294 deaths, of which we identified 1 363 (10%) SCD. Among autopsied SCD (n = 753, 55%), cause of death was myocarditis in 42 (6%) cases corresponding to an SCD-myocarditis incidence of 0.16 (95%CI: 0.11–0.21) per 100 000 person-years. Males had significantly higher incidence rates of SCD-myocarditis compared to females with an incidence rate ratio of 2.2 (95%CI: 1.1–4.1). Myocarditis was not registered as cause of death in any of the non-autopsied SCD (n = 610, 45%). In conclusion, after nationwide unselected inclusion of 14 294 deaths, we found that 6% of all autopsied SCD was caused by myocarditis. No cases of SCD-myocarditis were reported in the non-autopsied SCD, which could reflect underdiagnosing of myocarditis in non-autopsied SCD. Furthermore, our data suggest a female protection towards SCD-myocarditis.

A multiplex PCR strategy to screen for known mutations in families with sudden cardiac death burden.

Ventricular tachyarrythmia occurring in ischemic heart disease, dilated/hypertrophic cardiomyopathies or rare monogenic mutations of cardiac ion channels or associated proteins belong to the most frequent causes of sudden cardiac death (SCD). In further decades, next generation sequencing and bioinformatic analysis will become the gold standard of SCD risk stratification. At the moment, Sanger-sequencing is still obligatory in genetic diagnosis. A multiplex polymerase chain reaction (PCR) assay detecting eight SCD mutations in one reaction-tube was developed. To test the general validity of the assay, it was used with 12 patients, who had one or two of the eight mutations (LMNA, p.V256V; SCN5A, p.R1583C; RYR2, p.G1885E; MYH7, V606M; DSG2, p.T335A; KCNJ8, p.S422L; MYBPC, p.E441K; TNNT2, A38V). Thereafter, we tested the multiplex assay in a real diagnostic environment within a high risk family of several past SCD cases. This method allows efficient discrimination of multiple mutations by allele-specific PCR with standard PCR conditions. It relies on obtaining a PCR product specific to the mutation or wildtype—using primers that have the 3′end base complementary to the DNA template site, i.e. a specific primer only permits amplification to take place when its 3′terminal nucleotide matches with its target sequence. The PCR products are further analyzed by length, with Tape Station®(Agilent Technologies, Germany), a high-fidelity capillary chromatography test. The novel multiplex PCR assay strategy could be a good additional test used for SCD risk stratification. Advantages of the test are high velocity and ease of implementation, low price and flexibility of application within cardiomyopathy families for screening purposes.

Epidemiology of sudden cardiac death in Cameroon: the first population-based cohort survey in sub-Saharan Africa.

BackgroundIncidence estimates of sudden cardiac death (SCD) in sub-Saharan Africa (SSA) are unknown.MethodOver 12 months, the household administrative office and health community committee within neighbourhoods in two health areas of Douala, Cameroon, registered all deaths among 86 188 inhabitants aged >18 years. As part of an extended multi-source surveillance system, the Emergency Medical Service (EMS), local medical examiners and district hospital mortuaries were also surveyed. Whereas two physicians investigated every natural death, two cardiologists reviewed all unexpected natural deaths.ResultsThere were 288 all-cause deaths and 27 (9.4%) were SCD. The crude incidence rate was 31.3 [95% confidence interval (CI): 20.3–40.6]/100 000 person-years. The age-standardized rate by the African standard population was 33.6 (95% CI: 22.4–44.9)/100 000 person-years. Death occurred at night in 37% of cases, including 11% of patients who died while asleep. Out-of-hospital sudden cardiac arrest occurred in 63% of cases, 55.5% of which occurred at home. Of the 88.9% cases of witnessed cardiac arrest, 63% occurred in the presence of a family member and cardiopulmonary resuscitation was attempted only in 3.7%.ConclusionThe burden of SCD in this African population is heavy with distinct characteristics, whereas awareness of SCD and prompt resuscitation efforts appear suboptimal. Larger epidemiological studies are required in SSA in order to implement preventive measures, especially in women and young people.

002 Sudden cardiac death risk stratification in patients with mild dilated cardiomyopathy

Background The DANISH trial emphasised that the selection of patients with dilated cardiomyopathy (DCM) for implantable cardioverter defibrillators (ICD) needs to be improved. Registries demonstrate that the major burden of sudden cardiac death (SCD) occurs in those with a left ventricular ejection fraction (LVEF) >35%. Those at high-risk of SCD with milder reductions in LVEF may gain greater quality-adjusted life years from successful ICD therapy compared to those with more severe reductions, due to a lower risk of death from competing non-sudden causes. Variables that identify patients with milder reductions in LVEF at high-risk of SCD are required. Methods We prospectively investigated the utility of mid-wall late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) to predict SCD and aborted SCD in consecutive patients with DCM and LVEF >40% seen in our cardiomyopathy service or referred for CMR between 2000 and 2011. Those with potential pre-existing indications for ICD implantation were excluded. The presence of LGE was determined by a specialist blinded to clinical data. A panel blinded to CMR data adjudicated end-point occurrences. Results Of 399 patients (145 women, median age 50 years, median LVEF 50%) followed for a median of 4.6 years, 18 of 101 (17.8%) with LGE reached the pre-specified end-point, compared to 7 of 298 (2.3%) without (HR 9.2; 95% CI 3.9–21.8; p 5% compared to those without LGE were 10.6 (95%CI 3.9–29.4), 4.9 (95% CI 1.3–18.9) and 11.8 (95% CI 4.3–32.3). Conclusion Mid-wall LGE identifies patients with DCM and a LVEF >40% with an 8-fold increased risk of SCD and aborted SCD, who may benefit from ICD implantation. Acknowledgements BPH is supported by a British Heart Foundation Clinical Research Training Fellowship. The study has also been supported by the Alexander Jansons Foundation and CORDA.