Cases Of Sudden Cardiac Death Research Articles

The Value of Omega-3 Fatty Acids in the Prevention of Heart Rhythm Disorders

One of the trends in modern cardiology is the use of omega-3 polyunsaturated fatty acids ( ω -3 PUFA) in the prevention of heart rhythm disorders and the prevention of sudden cardiac death. In experimental studies, it was found that ω -3 PUFAs have a variety of pleiotropic effects: they reduce the formation of oxygen radicals, reduce reperfusion complications, reduce the level of thromboxane and platelet aggregation, and improve endothelial function. The ability of ω -3 PUFA to have an anti-inflammatory effect, which includes the inhibition of leukocyte chemotaxis, the expression of adhesion molecules, the formation of eicosanoids and biologically active substances with powerful anti-inflammatory properties. One of the most significant effects of ω -3 PUFA can be considered their anti-atherogenic effect. Antiarrhythmic properties of го -3 PUFA are associated with the effect on the ion channels of cardiomyocytes, they are able to activate slow calcium channels, increase the activity of Ca 2+ /Mg 2+ -ATPase and reduce the work of sodium channels. In animal experiments, it has been shown that in conditions of ischemia or adrenergic stimulation, ω -3 PUFA stabilizes the cardiomyocyte membrane, can increase the duration of the effective refractory period, and prevent the development of various heart rhythm disorders. Clinical studies have shown that the administration of ω -3 PUFA in addition to standard treatment reduces the risk of new cases of atrial fibrillation, ventricular arrhythmias and sudden cardiac death.

Etiology of Sudden Cardiac Arrest and Death in US Competitive Athletes: A 2-Year Prospective Surveillance Study.

To determine the etiology of sudden cardiac arrest and death (SCA/D) in competitive athletes through a prospective national surveillance program. Sudden cardiac arrest and death cases in middle school, high school, college, and professional athletes were identified from July 2014 to June 2016 through traditional and social media searches, reporting to the National Center for Catastrophic Sports Injury Research, communication with state and national high school associations, review of the Parent Heart Watch database, and search of student-athlete deaths on the NCAA Resolutions List. Autopsy reports and medical records were reviewed by a multidisciplinary panel to determine the underlying cause. US competitive athletes with SCA/D. Etiology of SCA/D. A total of 179 cases of SCA/D were identified (74 arrests with survival, 105 deaths): average age 16.6 years (range 11-29), 149 (83.2%) men, 94 (52.5%) whites, and 54 (30.2%) African American. One hundred seventeen (65.4%) had an adjudicated diagnosis, including 83 deaths and 34 survivors. The most common etiologies included hypertrophic cardiomyopathy (19, 16.2%), coronary artery anomalies (16, 13.7%), idiopathic left ventricular hypertrophy/possible cardiomyopathy (13, 11.1%), autopsy-negative sudden unexplained death (8, 6.8%), Wolff-Parkinson-White (8, 6.8%), and long QT syndrome (7, 6.0%). Hypertrophic cardiomyopathy was more common in male basketball (23.3%), football (25%), and African American athletes (30.3%). An estimated 56.4% of cases would likely demonstrate abnormalities on an electrocardiogram. The etiology of SCA/D in competitive athletes involves a wide range of clinical disorders. More robust reporting mechanisms, standardized autopsy protocols, and accurate etiology data are needed to better inform prevention strategies.

650The arrhythmic mitral valve prolapse: presentation and outcome

Abstract Background The majority of patients with of Mitral-valve-prolapse (MVP) have a excellent prognosis. Until recently most cases of mortality were thought to be related to mitral regurgitation and left ventricular dysfunction. The concept of the arrhythmic MVP emerged to describe cases of sudden cardiac death (SCD) in the presence of isolated MVP yet it’s phonotype remains incompletely and inconsistently defined. Purpose To analyze the prevalence, severity and characteristics of ventricular-arrhythmia (VA), to determine it’s phenotypical context and independent impact on outcome in patients with MVP. Methods A cohort of 595 (65 ± 16 years, 278 female) consecutive patients with MVP and comprehensive clinical, arrhythmia (24hour-Holter) and Doppler-echocardiographic characterization, was identified and long-term outcome analyzed. Results VA was frequent, present in 43% of patients with at least ventricular ectopy≥5%, but was most often moderate (ventricular-tachycardia—VT 120-179bpm) in 27% and rarely severe (VT≥180/min) in 8.6%. Presence of VA was associated with older age, male sex, bileaflet-prolapse, marked leaflet redundancy, mitral-annulus-disjunction (MAD), larger left-atrium and left ventricular end-systolic diameter, and T-wave-inversion/ST-depression (all P ≤ 0.001). Severe VA was independently associated with presence of MAD, leaflet-redundancy and T-wave-inversion/ST-depression (all P < 0.0001) but not with mitral regurgitation severity or ejection-fraction. Outcome primary endpoint of overall survival after arrhythmia diagnosis (8-year 87 ± 2%) was strongly associated with arrhythmia-severity (8-year 90 ± 2% for no/trivial arrhythmia, 85 ± 3% for mild/moderate and 76 ± 7% for severe arrhythmia. P = 0.02, Figure). Excess-mortality was substantial for severe-arrhythmia (univariate-hazard-ratio 2.70[1.27-5.77], P = 0.01 vs. no/trivial arrhythmia), even adjusted comprehensively including for MVP-characteristics (adjusted-hazard-ratio 2.94[1.36-6.36], P = 0.006) ). Conclusions This large cohort of isolated consecutive MVP characterized with 24-hour-Holter monitoring, clinical and Echocardiographic assessment, demonstrates that VA are frequent with MVP but rarely severe. The arrhythmic MVP was independently and strongly associated with specific ECG and morphologic patterns, particularly ST-T changes, MAD presence and marked leaflet redundancy, suggestive of a specific arrhythmic MVP phenotype, independently of MR-severity. Arrhythmia, particularly severe, is associated with long-term excess-mortality, independently of any other characteristics, including MR severity and LVEF. These findings lay the foundation for novel risk-stratification of MVP for the conduct of prospective controlled studies evaluating the management of MVP high-risk patients. Figure – Impact on survival of ventricular arrhythmia Overall survival of MVP stratified by ventricular arrhythmia (Panel A) or ventricular arrhythmia severity (Panel B) throughout follow-up. Abstract Figure.

The role of three-dimensional speckle tracking imaging derived parameters on predicting outcome of hypertrophic cardiomyopathy patients with MYH7 mutations

Objective: To evaluate the cardiac functional changes in hypertrophic cardiomyopathy(HCM) patients with β-myosin heavy chain gene (MYH7) mutations by three-dimensional (3D) speckle tracking imaging(3D-STI) and conventional echocardiography modalities, and then to explore the potential predictors of adverse cardiovascular events in these patients. Methods: A consecutive series of 192 HCM patients admitted in our center from October 2014 to October 2016 were genetically screened to identify MYH7 mutations in this retrospective study. A total of 43 HCM patients with MYH7 mutations were enrolled. The patients were divided into events group(n=13) and no event group(n=30) according to the presence or absence of adverse cardiovascular events(primary and secondary endpoints). All patients were followed up to January 2019 after comprehensive evaluation of 3D-STI, two-dimensional and Doppler echocardiography. The adverse cardiovascular events were recorded. Results: The median follow up time was 1 012 (812, 1 330) days. During follow-up, 13 patients (30.2%) reached endpoints: 6 cases of the primary endpoints(2 cases of sudden cardiac death(SCD), 3 cases of survival after defibrillation, and 1 case of appropriate implantable cardioverter-defibrillator(ICD) discharge); 7 cases of the second endpoints(5 cases of heart failure hospitalization, 1 case of syncope and cardioversion due to supraventricular tachycardia, and 1 case of end-stage HCM). Patients with adverse cardiovascular events had higher prevalence of syncope and risk of SCD, enlarged left atrial volume index(LAVI) and reduced 3D left ventricular global longitudinal train (3D-GLS), as compared to those without adverse events(all P<0.05). The multivariate Cox regression analysis showed that reduced 3D-GLS(HR=0.814, 95%CI 0.663-0.999, P=0.049) was an independent predictor for adverse cardiovascular events. The cutoff value of 3D-GLS≤13.67% was linked with significantly increased risk of adverse cardiovascular events in this patient cohort(AUC=0.753, 95%CI 0.558-0.948, sensitivity 86%, specificity 69%, P<0.05). The Kaplan-Meier analysis indicated that the patients with the 3D-GLS≤ 13.67% faced higher risk of death than those with 3D-GLS>13.67%. Conclusion: 3D-GLS is useful on predicting adverse cardiovascular events in HCM patients with MYH7 mutations.

Cost-effectiveness of in-home automated external defibrillators for children with cardiac conditions associated with risk of sudden cardiac death

Children at high risk for sudden cardiac death (SCD) (>6% over 5 years) receive an implantable cardioverter-defibrillator (ICD), but no guidelines are available for those at lower risk. For children at intermediate risk for SCD (4%-6% over 5 years), the utility and cost-effectiveness of in-home automated external defibrillators (AEDs) are unclear. The purpose of this study was to assess the cost-effectiveness of in-home AED for children at intermediate risk for SCD. Using hypertrophic cardiomyopathy (HCM) as the proxy disease, a theoretical cohort of 1550 ten-year-old children with HCM was followed for 69 years. Baseline annual risk of SCD was 0.8%. Outcomes were SCD, severe neurologic morbidity (SNM), cost, and quality-adjusted life-years (QALYs). Model inputs were derived from the literature, with a willingness-to-pay threshold of $100,000 per QALY. Among children at intermediate risk for SCD, in-home AED resulted in 31 fewer cases of SCD but 3 more cases of SNM. There were 319 QALYs gained. Although costs were higher by $28 million, the incremental cost-effectiveness ratio was $86,458, which is below the willingness-to-pay threshold. For children at intermediate risk for SCD and HCM, in-home AED is cost-effective, resulting in fewer deaths and increased QALYS for a cost below the willingness-to-pay threshold. These findings highlight the economic benefits of in-home AED use in this population.

Nonalcoholic Fatty Liver Disease as a Risk Factor for Prolonged Corrected QT Interval in Apparently Healthy Korean Women.

Nonalcoholic fatty liver disease (NAFLD) is clinically important because of its association with an increased risk of sudden cardiac death as well as liver-related mortality. Most cases of sudden cardiac death could be mediated by an arrhythmogenic process. Thus, we aimed to determine the association between NAFLD and corrected QT (QTc) interval in apparently healthy Korean women. This cross-sectional study included 764 women aged 20 to 74 years old who underwent a health examination program between 2014 and 2015. The QTc interval was calculated using Bazett's formula (QTc = QT/√RR). Multiple linear and logistic regression analysis were performed to assess independent relationships between NAFLD and QTc interval and prolonged QTc (≥ 450 milliseconds) was calculated after adjusting for confounding variables. The overall prevalence of NAFLD was 23.5% in general healthy women. The standardized β coefficient (95% confidence interval) of the QTc increment in patients with NAFLD was 6.4 milliseconds (1.2-11.8) through multiple linear regression analysis after adjusting for age, body mass index, smoking status, and regular exercise as well as mean arterial pressure, fasting plasma glucose, triglycerides, high-density lipoprotein cholesterol, aspartate aminotransferase, alanine aminotransferase, calcium, potassium levels and menopause status. Similarly, the odds ratio (95% confidence interval) of NAFLD for prolonged QTc was 2.05 (1.13-3.71) according to multiple logistic regression analysis after adjusting for the same covariables in women aged 20 to 74 years old. We demonstrated the arrhythmogenic potential of NAFLD, implying that careful monitoring of patient electrocardiograms is necessary to evaluate the possible arrhythmic risk in general healthy women with NAFLD.

Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death

QT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown. To evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death. This prospective countywide case-control study included World Health Organization-defined (presumed) SCD cases who underwent autopsy as part of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study (POST SCD) to determine arrhythmic or nonarrhythmic cause, and control deaths due to trauma (hereinafter referred to as trauma controls) in San Francisco County, California, from February 1, 2011, to March 1, 2014. Multivariate regression was used to evaluate the association of QTPM with the risk of presumed SCD, autopsy-defined SAD, and non-SAD compared with trauma controls. Medication exposure, determined by prescription lists and postmortem toxicologic findings, was used to calculate a summative QTPM exposure score (range, 0-20). Data were analyzed from September 1, 2018, to June 15, 2019. QT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high). Death due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause. A total of 629 patients (mean [SD] age, 61.4 [15.7] years; 439 men [69.8%]) were included, 525 with presumed SCDs and 104 traumatic death controls. Individuals with presumed SCDs had higher exposure and were more likely to be taking any QTPM (291 [55.4%] vs 28 [26.9%]; P < .001) than trauma controls. Use of QTPMs was associated with increased risk of presumed SCD in low (odds ratio [OR], 2.25 [95% CI, 1.03-4.96]; P = .04) and high (OR, 6.70 [95% CI, 1.47-30.67]; P = .01) exposure groups. After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD (low-risk OR, 2.88 [95% CI, 1.18-6.99; P = .02]; moderate-risk OR, 2.62 [95% CI, 1.20-5.73; P = .02]; and high-risk OR, 14.22 [95% CI, 2.91-69.30; P = .001]) but not SAD in all exposure groups. This association was attenuated by the exclusion of occult overdose non-SADs in the highest exposure group. These findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.

Short stature is associated with incident sudden cardiac death in a large Asian cohort

Few data on the association between height and the risk of sudden cardiac death (SCD) in Asian populations are available. The purpose of this study was to assess the risk of SCD as related to height both in a representative Korean population and in specific subgroups. This is a retrospective cohort study of 410,119 Koreans age ≥20 years from the Korean National Health Insurance Service-National Sample Cohort, who underwent a national health examination. SCD cases were adjudicated based on information within the claims database. Cox proportional hazard models were applied to estimate hazard ratios and 95% confidence intervals for the association between height and SCD. Potential mediators included demographic factors, health-related habits, and specific cardiovascular comorbidities. During an 8.45-year follow-up period, a total of 1341 SCDs occurred. Various factors, including short stature, were identified as risk factors for SCD. Multivariable regression analysis revealed that a 10-cm increase in height was associated with a 14% decreased risk for SCD. This relationship remained significant among the elderly, postmenopausal women, and individuals without cardiovascular disease. Our results indicate that short stature is a significant risk factor for SCD in a Korean population, thus supporting previously published findings correlating height to SCD risk in non-Asian populations.

Non-diagnostic autopsy findings in sudden unexplained death victims

BackgroundSeveral inherited cardiac diseases may lead to sudden cardiac death (SCD) a devastating event in the families. It is crucial to establish a post mortem diagnosis to facilitate relevant work-up and treatment of family members. Sudden unexplained death (SUD) victims constitute roughly one third of all SCD cases in Denmark.MethodsThis was a single center, retrospective study investigating SUD cases. Victims who died unexplained due to suspected or confirmed cardiac disease were consecutively referred to a third line referral center established in 2005. All autopsy reports were investigated. Victims were divided into two groups: non-diagnostic cardiac findings and normal cardiac findings. None of the included victims had findings consistent with a diagnosis based on existing criteria.ResultsIn total, 99 SUD cases were referred. The mean age of the victims was 37 years (range 0–62 years, 75% males). A total of 14 (14%) victims had a cardiovascular diagnosis pre-mortem. Thirty-seven cases had normal cardiac findings and non-diagnostic cardiac findings were found in 62 cases (63%). The five most common findings included ventricular hypertrophy and/or enlarged heart (n = 35, 35%), coronary atheromatosis (n = 31, 31%), myocardial fibrosis (n = 19, 19%), dilated chambers (n = 7, 7%) and myocardial inflammation (n = 5, 5%).ConclusionOne third of SUD victims had normal cardiac findings and non-diagnostic cardiac findings were seen in almost two thirds of the SUD victims. These non-diagnostic findings may be precursors or early markers for underlying structural cardiac disorders or may be innocent bystanders in some cases. Further studies and improved post-mortem examination methods are needed for optimization of diagnostics in SUD.

Clinical and genetic evaluation after sudden cardiac arrest

Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) can be attributed to cardiac, respiratory, metabolic, and toxicologic etiologies. Most cases of SCD are caused by coronary artery disease and approximately 40% of cardiac arrests are unexplained. Inherited arrythmias and cardiomyopathies are important contributors to SCA and SCD. Identifying an inherited condition after such an event not only has important ramifications for the individual, but also for relatives who may be at risk for the familial condition. This review will provide an overview of inherited cardiovascular disorders than can predispose to SCA/SCD, review the diagnostic evaluation for an individual and/or family after an SCA/SCD, and discuss the role of genetic testing.

Second opinion system for sudden cardiac death cases in forensic practice.

Sudden cardiac death (SCD) represents a considerable percentage of cardiovascular deaths worldwide. The most frequent pathological substrate of SCD is atherosclerotic coronary artery disease (CAD). The other, less common, pathologies which can cause SCD include cardiomyopathies, congenital diseases (including abnormal anatomy), and arrhythmias such as channelopathies, many of which are genetically determined. Autopsies of SCD victims are generally performed by forensic pathologists. In some cases, a third person responsibility could be invoked. While CAD diagnosis at post-mortem examination is not a major challenge for the forensic pathologist, the other rarer diseases may be. In such instances, referral of the hearts to specialized centers with recognized expertise is recommended, and this is particularly important in cases of SCDs of young people. Moreover, in order to avoid the frequent overdiagnosis of a pathological heart, an expert opinion should be sought for even in the presence of a morphologically normal heart. In cases where retention of the heart is not feasible, it is essential to provide an extensive photographic documentation, with the indication of the sampling sites for histological examination. However, some practical aspects, as the criteria for case selection in routine forensic practice are missing. In this paper, we present the recommendations for heart retention for a second expert opinion and the alternative of documentation and sampling for cases where retention is not possible.

НЕСТАБИЛЬНАЯ СТЕНОКАРДИЯ ИЛИ НЕСТАБИЛЬНЫЕ КОРОНАРНЫЕ СИНДРОМЫ?

Unstable angina pectoris (UA) is a variant of acute coronary syndrome without ST segment elevation (NSTEACS), which is characterized by the absence of biochemical criteria for myocardial damage, a change in the clinical picture of angina pectoris (an increase in the functional class of angina pectoris, the appearance of resting angina and a high probability of transformation of the process into myocardial infarction (MI). UA and the developed MI without ST segment elevation (NSTEMI) are not accompanied by the appearance of a pathological Q wave and are characterized by a general complex pathogenesis associated with progressive atherosclerosis, a non-occlusive thrombus in the area of erosion or rupture of an atherosclerotic plaque, vasospasm, coronary microcirculatory dysfunction or other causes of imbalance between oxygen intake and oxygen consumption resulting in myocardial ischemia, and are distinguished by increased levels of myocardial necrosis in the blood in case of NSTEMI. It is difficult to differentiate UA and NSTEMI in the first hours of the development of the process when a decision is made on reperfusion technologies and drug therapy without laboratory, and in some cases, additional examination with visualization of the probable new loss of viable myocardium, therefore, the diagnosis and management of these two clinical conditions are usually considered in the same clinical recommendations. A fairly common point of view that the risk of death in UA is significantly lower and the patient is less in need of an intensive strategy than with verified NSTEMI, is controversial given the likely cases of sudden cardiac death of ischemic genesis at the prehospital stage and the difficulties of differential diagnosis of these clinical states. The factors contributing to diagnostic errors include severity of the patient's condition, a variety of clinical atypical manifestations and pathophysiological mechanisms of myocardial ischemia, the presence of comorbid pathology. The article discusses various mechanisms of the development of myocardial ischemia, diagnostic and therapeutic invasive and non-invasive technologies that improve the prognosis of patients with UA. The optimal management tactics of NSTEACS includes early diagnosis and risk stratification, emergency hospitalization, monitoring, the use of non-invasive and invasive strategies, including coronary angiography and revascularization, as well as emergency and long-term treatment aimed at preventing acute cardiovascular events taking into account the age, gender differences and comorbid pathology. A differentiated approach to the administration of emergency therapy is the key to improving the prognosis of this high-risk category of patients. Due to the lack of the possibility of using revascularizing technologies in patients with obstructive coronary disease, non-pharmacological technologies that positively affect microcirculation processes are likely to be used: exposure of the patient’s blood to an alternating magnetic field (extracorporeal autohemomagnetotherapy) or to ultraviolet optical radiation (ultraviolet blood modification). In view of the difficulty in identifying the mechanism of myocardial ischemia in each individual patient with UA and a high likelihood of combination of various pathophysiological factors, myocardium rescue should be in the focus of therapeutic intervention, which dictates the validity and utility of all the recommended and available methods of pharmacological and non-pharmacological therapy and revascularization to reduce the effects of myocardial ischemia.

P859 Can we connect intraventricular exercise induced gradients to sudden cardiac death?

Abstract Background Some publications, on exercise induced intraventricular gradients, admit the possibility they can be related to some cases of unexplained sudden cardiac death (SCD). Clinical case We present the case of a young male athlete (16 years) that after winning a triathlon competition has sudden cardiac death. No cardiovascular risk factors. No family history of SCD A previous episode of dizziness, accompanied by nausea and vomiting related to intense training happens 6 months before. In September 2018 about 30 minutes after winning a triathlon competition has SCD episode having been resuscitated on site by the competition physician having been defibrillated and transported to intensive care unit. After discharge, cardiac MRI, Coronary AngioTC, complete genetic study for heart diseases, flecainid test, transthoracic echocardiogram, stress echocardiogram with hyperventilation and ergometrine. All have normal results (Figure) During 24 hours Holter ECG isolated premature ventricular complexes were detected and during exercise stress echocardiography a significant intraventricular gradient without systolic anterior movement of mitral valve was detected (Figure). The athlete was disqualified for sports practice, refuses CDI implantation and started bisoprolol 2,5 mg daily. To the best of our knowledge this is the first case of association between SCD and exercise induced intraventricular gradient. This possible association should be studied in the future. Abstract P859 Figure. Intraventricular gradient in SCD athlete

Прогностическое значение индекса массы тела в диагностике внезапной сердечной смерти

Objective: to determine the value of the body mass index (BMI) in cardiovascular patients for the sudden cardiac death (SCD) prediction. Materials and methods: we analyzed the medical archives of: 1) the Federal Research Clinical Center for Specialized Types of Healthcare and Medical Technologies, the Federal Biomedical Agency of Russia (comparison group I). The study included young athletes (N=603) without cardiovascular pathology, as well as those with cardiovascular diseases diagnosed in a medical examination; 2) Thanatological Department of the Bureau of Forensic Medical Examination (comparison group II). The sample (N=30) is represented by coronary heart disease (CHD) associated SCD cases; 3) the cardiac surgery Department of the Hospital of Emergency Medical Service (comparison group III). The sample (N=81) is represented by acute coronary syndrome (ACS) cases; 4) the cardiac surgery Department of the Clinic of Rostov State Medical University (comparison group IV). The sample (N=95) is represented by CHD patients who were on routine treatment. We calculated BMI in each comparison group. Results: in comparison group I, the BMI was 22.10±1.67 kg/m 2 , in group II-18.7±0.45 kg/m 2 , in group III – 28.01±0.58 kg/m 2 , in group IV – 28.66±0.47 kg/m 2 . The calculated value of χ 2 both for all groups and for their pairwise comparison was statistically significant (p<0.01), which suggests that there is a close association of obesity with an increased risk of CHD. Conclusions: the relationship between BMI and the presence of cardiovascular pathology in I comparison group (athletes) was not established. For groups II – IV, BMI is in a statistically significant association with cardiovascular pathology.

Sudden cardiac death among persons with diabetes aged 1-49 years: a 10-year nationwide study of 14 294 deaths in Denmark.

AimsThe aim of this study was to compare nationwide incidence rate (IR) of sudden cardiac death (SCD) in persons aged 1–49 years with and without diabetes mellitus (DM).Methods and resultsThe study population consisted of all persons in Denmark aged 1–49 years in 2000–09, which equals 27.1 million person-years. All 14 294 deaths in the 10-year period were included. By using the highly descriptive Danish death certificates, 1698 cases of sudden and unexpected death were identified. Through review of autopsy reports, discharge summaries, and the Danish registries, we identified 1363 cases of SCD. The Danish Register of Medicinal Product Statistics was used to identify persons with type 1 DM and type 2 DM. Among the 14 294 decedents, there were 669 with DM, of which 118 suffered SCD (9% of all SCD), making SCD the leading cause of death among young persons with DM. Among those aged 1–35 years, the IR of SCD-DM was 21.9 per 100 000 person-years compared to 2.6 per 100 000 person-years among persons without DM [IR ratio 8.6, 95% confidence interval (CI) 5.8–28.6]. Within the age range 36–49 years, the IR among persons with DM was 119.8 per 100 000 person-years compared to 19.7 per 100 000 person-years among persons without DM (IR ratio 6.1, 95% CI 4.7–7.8).ConclusionWe found that young persons with DM aged 1–35 years had >8-fold higher SCD IR compared to young persons without DM. Our study highlights the need for early cardiovascular risk monitoring and assessment in young persons with DM.

Targeted molecular genetic testing in young sudden cardiac death victims from Western Denmark.

Sudden unexpected death in the young continues to be an important unsolved challenge. A significant proportion of the deaths are suspected to be caused by inherited cardiac diseases and are referred to as sudden cardiac deaths (SCD). We performed targeted molecular testing of 70 deceased individuals under 40 years of age that after forensic autopsy were suspected to have died of SCD. The individuals were previously genetically investigated using smaller numbers of genes associated with specific cardiac diseases. In our previous studies, seven (10%) individuals had pathogenic or likely pathogenic variants according to the 2015 ACMG guidelines. In order to investigate the value of expanding the panel to 100 genes associated with cardiac diseases, we histopathologically re-examined the 70 suspected SCD cases and grouped them according to phenotypes into suspected cardiomyopathy (the cardiomyopathy group), left ventricular hypertrophy (the hypertrophy group) and structural normal hearts (the SUD group). DNA was captured with the Haloplex target enrichment system and sequenced using an Illumina MiSeq. We found that 11 (16%) individuals harboured pathogenic or likely pathogenic variants. In the cardiomyopathy, hypertrophy and SUD groups, 22%, 6% and 17% of the individuals, respectively, harboured pathogenic or likely pathogenic variants. Our findings show that testing of a broad panel of genes associated with cardiac diseases identify potential pathogenic variants of cardiac diseases in a significant proportion of SCD cases, and this may have important implications in family screening to prevent future deaths.

Rare Genetic Variants Associated With Sudden Cardiac Death in Adults

BackgroundSudden cardiac death occurs in ∼220,000 U.S. adults annually, the majority of whom have no prior symptoms or cardiovascular diagnosis. Rare pathogenic DNA variants in any of 49 genes can pre-dispose to 4 important causes of sudden cardiac death: cardiomyopathy, coronary artery disease, inherited arrhythmia syndrome, and aortopathy or aortic dissection. ObjectivesThis study assessed the prevalence of rare pathogenic variants in sudden cardiac death cases versus controls, and the prevalence and clinical importance of such mutations in an asymptomatic adult population. MethodsThe authors performed whole-exome sequencing in a case-control cohort of 600 adult-onset sudden cardiac death cases and 600 matched controls from 106,098 participants of 6 prospective cohort studies. Observed DNA sequence variants in any of 49 genes with known association to cardiovascular disease were classified as pathogenic or likely pathogenic by a clinical laboratory geneticist blinded to case status. In an independent population of 4,525 asymptomatic adult participants of a prospective cohort study, the authors performed whole-genome sequencing and determined the prevalence of pathogenic or likely pathogenic variants and prospective association with cardiovascular death. ResultsAmong the 1,200 sudden cardiac death cases and controls, the authors identified 5,178 genetic variants and classified 14 as pathogenic or likely pathogenic. These 14 variants were present in 15 individuals, all of whom had experienced sudden cardiac death—corresponding to a pathogenic variant prevalence of 2.5% in cases and 0% in controls (p < 0.0001). Among the 4,525 participants of the prospective cohort study, 41 (0.9%) carried a pathogenic or likely pathogenic variant and these individuals had 3.24-fold higher risk of cardiovascular death over a median follow-up of 14.3 years (p = 0.02). ConclusionsGene sequencing identifies a pathogenic or likely pathogenic variant in a small but potentially important subset of adults experiencing sudden cardiac death; these variants are present in ∼1% of asymptomatic adults.

Hypertrophic Cardiomyopathy-Related Sudden Cardiac Death in Young People in Ontario.

Hypertrophic cardiomyopathy (HCM) is considered a leading cause of sudden cardiac death (SCD) in younger people. The incidence of HCM-related SCD and its relationship to exercise have not been well studied in large comprehensive studies outside of tertiary care settings. This study sought to estimate the incidence of HCM-related SCD and its association with exercise in a large unselected population. Using the Office of the Chief Coroner of Ontario database encompassing all deaths attended by the coroner, we identified all HCM-related SCDs in individuals 10 to 45 years of age between 2005 and 2016 (70 million person-years). Confirmation of HCM was based on typical macroscopic and microscopic features (definite HCM-related SCD). Sudden deaths with a prior clinical diagnosis of HCM but no autopsy were considered probable HCM-related SCDs. Cases with typical features but no myofiber disarray were considered possible HCM. The completeness of data was verified in a subset of patients in the Toronto area with the use of a registry of all emergency medical services-attended cardiac arrests, with an autopsy rate of 94%. To estimate the number of HCM-related aborted cardiac arrests and lives potentially saved by implantable cardioverter-defibrillators, all de novo implantations for secondary prevention and all implantations and appropriate shocks for primary prevention in patients with HCM 10 to 45 years of age, respectively, were identified with the use of a registry containing data on implantable cardioverter-defibrillator implantations from all implanting sites throughout Ontario. Forty-four, 3, and 6 cases of definite, probable, and possible HCM-related SCDs, respectively, were identified, corresponding to estimated annual incidence rates of 0.31 per 1000 HCM person-years (95% CI, 0.24-0.44) for definite HCM-related SCD, 0.33 per 1000 HCM person-years (95% CI, 0.34-0.62) for definite or probable HCM-related SCD, and 0.39 per 1000 HCM person-years (95% CI, 0.28-0.49) for definite, probable, or possible HCM-related SCD (estimated 140 740 HCM person-years of observation). The estimated annual incidence rate for HCM-related SCD plus aborted cardiac arrest and HCM-related life-threatening arrhythmia (SCD, aborted cardiac arrest, and appropriate implantable cardioverter-defibrillator shocks) was 0.84 per 1000 HCM person-years (95% CI, 0.70-1.0). The majority (70%) of SCDs occurred in previously undiagnosed individuals. Most SCDs occurred during rest (64.8%) or light activity (18.5%). The incidence of HCM-related SCD in the general population 10 to 45 years of age is substantially lower than previously reported, with most cases occurring in previously undiagnosed individuals. SCDs are infrequently related to exercise.

An association between right ventricular dysfunction and sudden cardiac death

The effectiveness of severely reduced left ventricular ejection fraction (LVEF <35%) as a predictor of sudden cardiac death (SCD) has diminished, and improvements in risk stratification await discovery of novel markers. Right ventricular (RV) abnormalities can be observed in conditions such as chronic obstructive pulmonary disease and sleep apnea, which have been linked to SCD. The purpose of this study was to evaluate whether RV abnormalities were associated with SCD after accounting for LVEF and other patient characteristics. In a large, prospective ongoing community-based study of SCD in the Portland, Oregon, metropolitan area, SCD cases (age ≥18 years; 2002-2014) were compared to controls with coronary artery disease but no SCD. Using a novel archive of digital echocardiograms, a standardized approach was used to evaluate RV basal diameter, RV end-diastolic area, and right ventricular fractional area change (RVFAC). A total of 350 subjects were studied, including 81 SCD cases (age 68.7 ± 13.6 years; 73% male) and 269 controls (age 66.5 ± 10.2 years; 69% male). In multivariate analysis, RVFAC was significantly associated with SCD (odds ratio 1.14 for each 5% decrease; 95% confidence interval 1.03-1.25; P = .01). When modeled with LVEF ≤35%, RVFAC ≤35% was significantly associated with increased risk of SCD. Individuals with both left ventricular and RV dysfunction had a 3× higher odds of SCD than those with neither (odds ratio 3.19; 95% confidence interval 1.33-7.68; P = .01). RV dysfunction was associated with a significantly increased risk of SCD independent of LVEF and, when combined with LVEF, had additive effects on SCD risk.

Prolonged Tpeak -Tend interval is a risk factor for sudden cardiac death in adults with congenital heart disease.

ObjectiveAdult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). However, methods for risk stratification are not yet well‐defined. The Tpeak‐Tend (TpTe) interval, a measure of dispersion of ventricular repolarization, is a risk factor for SCD in non‐ACHD patients. We aim to evaluate whether TpTe can be used in risk stratification for SCD in ACHD patients.DesignFrom an international multicenter cohort of 25 790 ACHD patients, we identified all SCD cases. Cases were matched to controls by age, gender, congenital defect, and (surgical) intervention.Outcome MeasuresTpTe was measured on a standard 12‐lead ECG. The maximum TpTe of all ECG leads (TpTe‐max), mean (TpTe‐mean), and TpTe dispersion (maximum minus minimum) were obtained. Odds ratios (OR) for SCD cases vs controls were calculated using conditional logistic regression analysis.ResultsECGs were available for 147 cases (median age at death 33.5 years (quartiles 26.2, 48.7), 66% male) and 267 controls. The mean TpTe‐max was 97 ± 24 ms in cases vs 84 ± 17 ms in controls (P < .001); TpTe‐mean was 70 ± 16 vs 63 ± 10 ms (P < .001); and dispersion was 51 ± 22 ms vs 41 ± 16 ms (P = .02), respectively. Assessing each ECG lead separately, TpTe in lead aVR predicted SCD most accurately. TpTe in lead aVR was 71 ± 23 ms in cases vs 61 ± 13 ms in controls (P < .001). After adjusting for impaired ventricular function, heart failure symptoms, and prolonged QRS duration, the OR of SCD of TpTe in lead aVR at an optimal cutoff of 80 ms was 5.8 (95% CI 2.7‐12.4, P < .001).ConclusionsThe TpTe interval is associated with SCD in ACHD patients. Particularly, TpTe in lead aVR can be used as an independent risk factor for SCD in ACHD patients and may, therefore, add precision to current risk prediction models.