Nationwide study of mortality and sudden cardiac death in young persons diagnosed with chronic kidney disease.

AIMS: The aim of this study was to compare short- and long-term risk of sudden cardiac death (SCD) among persons aged 18-49 years with and without chronic kidney disease (CKD). METHODS AND RESULTS: Using Danish nationwide health registries, all persons aged 18-49 years diagnosed with earlier stages of CKD or chronic kidney failure from 1 July 1995 through 2009 were identified. Non-exposed subjects matched on sex and birth-year were identified. All SCD in the Danish population aged 18-49 years in 2000-2009 have previously been identified using information from the Danish nationwide health registries, death certificates, and autopsy reports. In total, 9308 incident cases of earlier stage CKD and 1233 incident cases of chronic kidney failure were included. Among patients with earlier stage CKD, the absolute risk of SCD 1, 5, and 10 years after diagnosis was 0.14%, 0.37%, and 0.68%, respectively. Compared with age- and sex-matched subjects the corresponding relative risk (RR) was 20.3 [95% confidence interval (CI) 8.4-48.8], 7.1 (95% CI 4.2-12.0), and 6.1 (95% CI 3.8-9.7), respectively. Among patients with chronic kidney failure, the absolute 1-, 5-, and 10-year risk of SCD was 0.17%, 0.56%, and 2.07%, respectively. The corresponding RR was 12.5 (95% CI 1.4-111.6), 7.9 (95% CI 2.3-27.0), and 10.1 (95% CI 4.5-22.6). CONCLUSION: Persons with earlier stage CKD and chronic kidney failure had increased risk of SCD compared with the background population with a 6- to 20-fold increased risk of SCD. These findings underline the importance of early cardiovascular risk monitoring and assessment in persons with CKD.

Witnessed and unwitnessed sudden cardiac death: a nationwide study of persons aged 1-35 years.

AIMS: The aim of this study is to compare clinical characteristics and causes of death among witnessed and unwitnessed sudden cardiac death (SCD) cases aged 1-35 years. METHODS AND RESULTS: In this retrospective nationwide study, all deaths in persons aged 1-35 years in Denmark during 2000-09 were included (23.7 million person-years). Using the in-depth descriptive Danish death certificates and Danish nationwide registries, 860 cases of sudden, unexpected death were identified. Through review of autopsy reports and register data, we identified 635 cases of SCD of which 266 (42%) were witnessed and 326 (51%) were unwitnessed. In 43 cases (7%), witnessed status was missing. Clinical characteristics were overall similar between the two groups. We found a male predominance among unwitnessed SCD compared to witnessed SCD (71% and 62%, respectively, P-value 0.012), as well as more psychiatric comorbidity (20% and 13%, respectively, P-value 0.029). Unwitnessed SCD more often occurred during sleep whereas witnessed SCD more often occurred while the individual was awake and relaxed (P-value < 0.001). The autopsy rate among all SCD cases was 70% with no significant difference in autopsy rate between the two groups. Sudden unexplained death, which was the leading autopsy conclusion in both groups, was more frequent among unwitnessed SCD (P-value 0.001). CONCLUSION: Several clinical characteristics and autopsy findings were similar between witnessed and unwitnessed SCD cases. Our data support the inclusion of both witnessed and unwitnessed cases in epidemiological studies of SCD cases aged 1-35 years, although the risk of misclassification is higher among unwitnessed and non-autopsied cases of SCD.

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

AIMS: The 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 RESULTS: The 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). CONCLUSION: We 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.

Impact of Physician-staffed Helicopters on Pre-hospital Patient Outcomes: A systematic review.

BACKGROUND: Management of pre-hospital patients remains a challenge. In developed countries a physician-staffed helicopter emergency medical service (PS-HEMS) is used in addition to ground emergency medical service (GEMS), but the effect is debated. This systematic review aimed to evaluate the effect of PS-HEMS compared with GEMS on patient outcomes based on the published scientific literature. METHODS: Medline, EMBASE and the Cochrane Library were systematically searched on November 15, 2019 for prospective, interventional studies comparing outcomes of patients transported by either PS-HEMS or GEMS. Outcomes of interest were mortality, time to hospital and quality of life. RESULTS: The majority of 18 studies included were observational and difficult to summarize because of heterogeneity. Meta-analysis could not be carried out. Three studies found reduced mortality in patients transported by PS-HEMS compared with GEMS with Odds ratios (OR) of 0.68 (0.47-0.98); 0.29 (0.10-0.82) and 0.21 (0.06-0.73) respectively. Another two studies found improved survival with OR 1.2 (1.0-1.5) and 6.9 (1.48-32.5) in patients transported by PS-HEMS compared with GEMS. In three studies, PS-HEMS was associated with shorter time to hospital. Three studies reported quality of life and found no benefit of PS-HEMS. CONCLUSION: In this systematic review the studies comparing PS-HEMS with GEMS were difficult to summarize because of heterogeneity. We found a possible survival benefit of PS-HEMS but were unable to conduct a meta-analysis. The overall quality of evidence was low.

Decline in incidence of sudden cardiac death in the young: a 10-year nationwide study of 8756 deaths in Denmark.

AIMS: Sudden cardiac death in the young (SCDY) accounts for a significant proportion of deaths among the young. The aim of this nationwide study was to examine temporal changes in incidence and causes of SCDY in Denmark in 2000-2009. During this 10-year period, several public and private health initiatives were undertaken to decrease morbidity and mortality in Denmark. METHODS AND RESULTS: All deaths among persons aged 1-35 years in Denmark in 2000-2009 (23.7 million person-years) were included. Death certificates, autopsy reports, discharge summaries, and data from nationwide administrative registries were used to identify SCDY cases. Sudden cardiac death in the young incidence rates were age-adjusted and sex-adjusted using direct standardization. Temporal changes in standardized SCDY incidence rates were reported as average annual percent changes. In the 10-year study period, there were 8756 deaths, of which we identified 635 (7%) SCDY cases. For these SCDY cases, median age at death was 29 years and 68% were men. Standardized incidence of SCDY decreased from 3.1 per 100 000 person-years in 2000 [95% confidence interval (CI) 2.4-3.8] to 2.5 per 100 000 person-years in 2009 (95% CI 1.9-3.2). This corresponds to an average annual percent change of -3.0% (95% CI -5.8 to -0.1). The distribution of major causes of SCDY did not change significantly throughout the study period. CONCLUSION: Incidence of SCDY decreased significantly from 2000 through 2009 in Denmark with an average annual percent change of -3%. Further research is needed to elucidate underlying causes of this development.

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

Aims: Febrile seizure (FS) is a common disorder affecting 2-5% of children up to 5 years 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). Methods and results: 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 (71 027/2 369 785; 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%). Conclusion: 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.

Post-mortem toxicology in young sudden cardiac death victims: a nationwide cohort study.

Aims: Several drugs increase the risk of ventricular fibrillation and sudden cardiac death (SCD). We aimed to investigate in detail the toxicological findings of all young SCD throughout Denmark. Methods and results: Deaths in persons aged 1-49 years were included over a 10-year period. Death certificates and autopsy reports were retrieved and read to identify cases of sudden death and establish cause of death. All medico-legal autopsied SCD were included and toxicological reports collected. Positive toxicology was defined as the presence of any substance (licit and/or illicit). All toxicological findings had previously been evaluated not to have caused the death (i.e. lethal concentrations were excluded). We identified 620 medico-legal autopsied cases of SCD, of which 77% (n = 477) were toxicologically investigated post-mortem, and 57% (n = 270) had a positive toxicology profile. Sudden cardiac death with positive toxicology had higher rates of sudden arrhythmic death syndrome (SADS), compared with SCD with negative toxicology (56% vs. 42%, P < 0.01). In total, 752 agents were detected, and polypharmacy (defined as the presence of more than one drug) was present in 61% (n = 164), all substances combined. Psychotropic drugs were the most frequent (62%, n = 467), and 82% (n = 385) were in pharmacological or subpharmacological levels. Conclusion: We found that more than half of all toxicologically investigated SCD victims have positive post-mortem toxicological findings, and polypharmacy is displayed in a considerable proportion. SCD with positive toxicology had higher rate of SADS, suggesting that the compounds may play a proarrhythmic role in these cases.

Association of common genetic variants related to atrial fibrillation and the risk of ventricular fibrillation in the setting of first ST-elevation myocardial infarction.

BACKGROUND: Cohort studies have revealed an increased risk for ventricular fibrillation (VF) and sudden cardiac death (SCD) in patients with atrial fibrillation (AF). In this study, we hypothesized that single nucleotide polymorphisms (SNP) previously associated with AF may be associated with the risk of VF caused by first ST-segment elevation myocardial infarction (STEMI). METHODS: We investigated association of 24 AF-associated SNPs with VF in the prospectively assembled case-control study among first STEMI-patients of Danish ancestry. RESULTS: We included 257 cases (STEMI with VF) and 537 controls (STEMI without VF). The median age at index infarction was 60 years for the cases and 61 years for the controls (p = 0.100). Compared to the control group, the case group was more likely to be male (86% vs. 75%, p = 0.001), have a history of AF (7% vs. 2%, p = 0.006) or hypercholesterolemia (39% vs. 31%, p = 0.023), and a family history of sudden death (40% vs. 25%, p < 0.001). All 24 selected SNPs have previously been associated with AF. None of the 24 SNPs were associated with the risk of VF after adjustment for age and sex under additive genetic model of inheritance in the logistic regression model. CONCLUSION: In this study, we found that the 24 AF-associated SNPs may not be involved in increasing the risk of VF. Larger VF cohorts and use of new next generation sequencing and epigenetic may in future identify additional AF and VF risk loci and improve our understanding of genetic pathways behind the two arrhythmias.

Gender differences in sudden cardiac death in the young-a nationwide study.

BACKGROUND: Hitherto, sudden cardiac death (SCD) in the young has been described with no distinction between genders. SCD occurs more often in men (SCDm) than women (SCDw), but this disparity is not understood and has not been investigated systematically in a nationwide setting. Our objective was to report gender differences in SCD in the young in a nationwide (Denmark) setting. METHODS: All deaths in persons aged 1-35 years nationwide in Denmark between 2000 and 2009 were included. Death certificates and autopsy reports were obtained. The extensive health care registries in Denmark were used to investigate any known disease prior to death. SCDw were compared to SCDm. RESULTS: During the 10-year study period there were a total of 8756 deaths in 23.7 million person-years. In total, 635 deaths were SCD. SCDw constituted 205 deaths (32%). Women had a higher proportion of witnessed deaths (51 vs. 41%, p = 0.02) and died less often in a public place (16 vs. 26%, p = 0.01). Age at death, ratios of autopsies and sudden unexplained deaths, and comorbidities, did not differ. Causes of SCD were largely comparable between genders. The incidence rate of SCDw was half of that of SCDm (1.8 vs. 3.6 per 100,000 person-years, incidence rate ratio 2.0 (95% CI 1.7-2.4), p < 0.01). CONCLUSIONS: Incidence rate ratio of SCDm vs SCDw is 2. Young SCDw and SCDm are equally investigated, have comparable comorbidity, and causes of SCD. SCD due to potentially inherited cardiac diseases is less often in young women and could reflect a protection of female gender.

Survival After Out-of-Hospital Cardiac Arrest in Relation to Age and Early Identification of Patients With Minimal Chance of Long-Term Survival.

BACKGROUND: Survival after out-of-hospital cardiac arrest has increased during the last decade in Denmark. We aimed to study the impact of age on changes in survival and whether it was possible to identify patients with minimal chance of 30-day survival. METHODS AND RESULTS: Using data from the nationwide Danish Cardiac Arrest Registry (2001─2011), we identified 21 480 patients ≥18 years old with a presumed cardiac-caused out-of-hospital cardiac arrest for which resuscitation was attempted. Patients were divided into 3 preselected age-groups: working-age patients 18 to 65 years of age (33.7%), early senior patients 66 to 80 years of age (41.5%), and late senior patients >80 years of age (24.8%). Characteristics in working-age patients, early senior patients, and late senior patients were as follows: witnessed arrest in 53.8%, 51.1%, and 52.1%; bystander cardiopulmonary resuscitation in 44.7%, 30.3%, and 23.4%; and prehospital shock from a defibrillator in 54.7%, 45.0%, and 33.8% (all P<0.05). Between 2001 and 2011, return of spontaneous circulation on hospital arrival increased: working-age patients, from 12.1% to 34.6%; early senior patients, from 6.4% to 21.5%; and late senior patients, from 4.0% to 15.0% (all P<0.001). Furthermore, 30-day survival increased: working-age patients, 5.8% to 22.0% (P<0.001); and early senior patients, 2.7% to 8.4% (P<0.001), whereas late senior patients experienced only a minor increase (1.5% to 2.0%; P=0.01). Overall, 3 of 9499 patients achieved 30-day survival if they met 2 criteria: had not achieved return of spontaneous circulation on hospital arrival and had not received a prehospital shock from a defibrillator. CONCLUSIONS: All age groups experienced a large temporal increase in survival on hospital arrival, but the increase in 30-day survival was most prominent in the young. With the use of only 2 criteria, it was possible to identify patients with a minimal chance of 30-day survival.

Cardiac symptoms before sudden cardiac death caused by hypertrophic cardiomyopathy: a nationwide study among the young in Denmark.

AIMS: Hypertrophic cardiomyopathy (HCM) is a frequent cause of sudden cardiac death (SCD) among the young (SCDY). The aim of this study was to characterize symptoms before SCDY due to HCM. METHODS AND RESULTS: Through review of all death certificates, we identified all SCDs in Danes aged 1-35 years in 2000-2009. Nationwide we included all deaths (n = 8756) and identified 431 autopsied SCDYs. All available records from hospitals and general practitioners were retrieved. To compare symptoms, we included a control groups consisting of traffic accident victims (n = 74). In the 10-year study period, 431 autopsied SCDY cases were reviewed and 38 cases (9%) were included, of which 22 (58%) had morphologic findings diagnostic of HCM and 16 (42%) had findings suggestive, but not diagnostic, of HCM ('possible HCM'). Cardiac symptoms >1 h prior to death were reported in 21 (55%) of cases, and 16 (42%) sought medical attention. One (1%) control had cardiac symptoms before death. Consequently, a significantly higher proportion of cases had cardiac symptoms before death and cases more often sought medical attention than controls (P < 0.001). CONCLUSION: In conclusion, this nationwide study demonstrates a high frequency of cardiac symptoms prior to death in SCDY cases who died of HCM, as 55% had cardiac symptoms and nearly half of the cases sought medical attention.

Symptoms Before Sudden Arrhythmic Death Syndrome: A Nationwide Study Among the Young in Denmark.

INTRODUCTION: No studies in an unselected and nationwide setting have characterized the symptoms and medical history of patients with sudden arrhythmic death syndrome (SADS). The aim of this study was to identify and describe the symptoms and medical history of patients before the presentation of SADS. METHODS AND RESULTS: We have previously identified all of the autopsied sudden cardiac deaths (SCD; n = 314) in Danes aged 1-35 years between 2000 and 2006. After comprehensive pathological and toxicological investigation did not reveal a cause of SCD, 136 of the patients were identified as SADS. The National Patient Registry was utilized to obtain information on all in- and outpatient activity in Danish hospitals. All medical records from hospitals and general practitioners, including death certificates and autopsy reports were reviewed. Before death, 48 (35%) SADS patients had cardiac symptoms; among these, 30 (22%) had contacted the healthcare system. Antecedent symptoms (symptoms >24 hours before death) were present in 34 (25%) patients. Prodromal symptoms (symptoms ≤24 hours before death) were present in 23 (17%) patients. Cardiac symptoms included chest pain (n = 16, 12%), dyspnea (n = 18, 13%), palpitations (n = 2, 1%), presyncope/syncope (n = 23, 17%), and aborted SCD (n = 2, 1%). In addition, seizures (n = 25, 18%) were prevalent. In 61 (45%) SADS cases, no previous medical history were recorded. CONCLUSION: In this unselected, nationwide study of 136 young SADS patients, 35% had experienced cardiac symptoms before death, most commonly presyncope/syncope, but only one out of five had contacted a healthcare provider with cardiac symptoms.

Sudden death in young persons with uncontrolled asthma--a nationwide cohort study in Denmark.

BACKGROUND: Asthma is a common chronic disease among young adults, and several studies have reported increased mortality rates in patients with asthma. However, no study has described sudden unexpected death in a nationwide setting in patients with uncontrolled asthma. We defined uncontrolled asthma as a previous hospital admittance because of asthma (of any severity) or when asthma was considered to have influenced the death according to the death certificate. The purpose of this study is to increase the medical focus on young persons with uncontrolled asthma and thereby hopefully aid in preventing sudden unexpected deaths. We therefore aimed to describe clinical characteristics, symptoms, causes of death, and contact with the healthcare system prior to sudden unexpected death in young persons with uncontrolled asthma. METHODS: Through the review of death certificates, we found 625 sudden unexpected death cases in individuals aged 1-35 years in Denmark from 2000 to 2006. Of those, 49 persons with uncontrolled asthma were identified. Previous contacts with the healthcare system were identified, and available records from general practitioners were retrieved. RESULTS: We identified 49 individuals who suffered from uncontrolled asthma. This corresponds to an incidence rate of 0.32 per 100,000 person-years. The cause of death in 31 cases (63%) was sudden cardiac death, and in 13 cases (27%), it was a fatal asthma attack. Symptoms (chest pain, dyspnea, seizures, general malaise, syncope, and palpitations) prior to death were reported in 41 (84%) of the cases. In 34 (69%) of the cases, antecedent symptoms (symptoms >24 hours before death) were present, and 28 (57%) patients had prodromal symptoms (symptoms <24 hours before death). The most common antecedent symptoms were dyspnea and chest pain, whereas the most common prodromal symptoms were dyspnea, general malaise, and/or fatigue. Twenty-eight patients (57%) sought medical advice from a general practitioner and/or emergency department due to these symptoms. CONCLUSION: The cause of death was predominantly sudden cardiac death followed by fatal asthma attack. We found that 41 (84%) of patients suffered from symptoms prior to death and that 28 (57%) sought medical advice from the emergency department and/or general practitioners.

Sudden cardiac death in children (1-18 years): symptoms and causes of death in a nationwide setting.

AIMS: Hitherto, sudden cardiac death in children (SCDc)-defined as sudden cardiac death (SCD) in the 1-18 years old-has been incompletely described in the general population. Knowledge on incidence rates, causes of death and symptoms prior to death is sparse and has been affected by reporting and referral bias. METHODS AND RESULTS: In a nationwide setting all deaths in children aged 1-18 years in Denmark in 2000-06 were included. To chart causes of death and incidence rates, death certificates and autopsy reports were collected and read. By additional use of the extensive healthcare registries in Denmark, we were also able to investigate prior disease and symptoms. During the 7-year study period there was an average of 1.11 million persons aged 1-18 years. There were a total of 1504 deaths (214 deaths per year) from 7.78 million person-years. A total of 114 (7.5%) were sudden and unexpected. A cardiac disease was known prior to death in 18% of all sudden unexpected death cases. In two-thirds of all sudden unexpected death cases no previous medical history was registered. Causes of death in autopsied cases were cardiac or unknown in 70%. Unexplained deaths, presumed to be a primary cardiac arrhythmia, accounted for 28% of autopsied sudden unexpected death cases. Autopsy rate was 77%. There were a total of 87 cases of SCDc (5.8% of all deaths). Prodromal symptoms were noted in 26% and antecedent symptoms in 45% of SCDc cases. The most frequent antecedent symptoms were seizures, dyspnoea, and syncope. In total, 61% of SCDc were not known with any prior disease; 23% were known with congenital or other heart disease prior to death. In total, 43 (49%) of all sudden unexpected deaths died of a potential inherited cardiac disease. The incidence rate of sudden unexpected death was 1.5 per 100 000 person-years. The highest possible incidence rate of SCDc was 1.1 per 100 000 person-years. CONCLUSION: From a nationwide study of all deaths in a 7-year period more than half of all victims of SCDc experienced antecedent and/or prodromal symptoms prior to death. The incidence rate of sudden death and SCDc was 1.5 and 1.1 per 100 000 person-years, respectively. Cardiac symptoms in young persons should warrant clinical work-up and an autopsy should be performed in all cases of sudden unexpected death in which the deceased was not known with congenital heart disease prior to death. This is pivotal, in the subsequent familial cascade screening, to diagnose and treat potential inherited cardiac diseases in family members.

New population-based exome data question the pathogenicity of some genetic variants previously associated with Marfan syndrome.

BACKGROUND: Marfan syndrome (MFS) is a rare autosomal dominantly inherited connective tissue disorder with an estimated prevalence of 1:5,000. More than 1000 variants have been previously reported to be associated with MFS. However, the disease-causing effect of these variants may be questionable as many of the original studies used low number of controls. To study whether there are possible false-positive variants associated with MFS, four in silico prediction tools (SIFT, Polyphen-2, Grantham score, and conservation across species) were used to predict the pathogenicity of these variant. RESULTS: Twenty-three out of 891 previously MFS-associated variants were identified in the ESP. These variants were distributed on 100 heterozygote carriers in 6494 screened individuals. This corresponds to a genotype prevalence of 1:65 for MFS. Using a more conservative approach (cutoff value of >2 carriers in the EPS), 10 variants affected a total of 82 individuals. This gives a genotype prevalence of 1:79 (82:6494) in the ESP. A significantly higher frequency of MFS-associated variants not present in the ESP were predicted to be pathogenic with the agreement of ≥3 prediction tools, compared to the variants present in the ESP (p = 3.5 × 10-15). CONCLUSIONS: This study showed a higher genotype prevalence of MFS than expected from the phenotype prevalence in the general population. The high genotype prevalence suggests that these variants are not the monogenic cause of MFS. Therefore, caution should be taken with regard to disease stratification based on these previously reported MFS-associated variants.

Risk of cardiovascular disease in family members of young sudden cardiac death victims.

AIMS: Descriptive and genetic studies suggest that relatives of sudden cardiac death (SCD) victims have an increased risk of several cardiovascular diseases (CVDs). Given the severe consequences of undiagnosed CVD and the availability of effective treatment, the potential for prevention in this group is enormous if they do have an increased CVD risk. This nationwide prospective population-based cohort study described the risk of CVDs in relatives of young SCD victims, compared with the general population. METHODS AND RESULTS: All SCD victims aged 1-35 years in Denmark, 2000-2006, were identified (n = 470), along with their first- and second-degree relatives (n = 3073). We compared the incidence of CVD in those relatives with that in the background population using standardized incidence ratios (SIRs). The observed number of CVDs over 11 years of follow-up was 292, compared with 219 expected based on national rates [SIR 1.33, 95% confidence interval (CI) 1.19-1.50]. Risks varied significantly with age; the SIR for those <35 years was 3.53 (95% CI 2.65-4.69), compared with SIRs of 1.59 (95% CI 1.35-1.89) and 0.91 (95% CI 0.75-1.10) for those aged 35-60 years or >60 years, respectively (P(homogeneity) < 0.0001). For first-degree relatives <35 years, SIRs for ischaemic heart disease, cardiomyopathy, and ventricular arrhythmia were 5.99 (95% CI 1.95-0.13.98), 17.91 (95% CI 4.88-45.87), and 19.15 (95% CI 7.70-39.45), respectively. CONCLUSION: CVDs co-aggregated significantly with SCD in families, with young first-degree relatives at greatest risk. Results clearly indicate that family members of young SCD victims should be offered comprehensive and systematic screening, with focus on the youngest relatives.

Epilepsy and risk of death and sudden unexpected death in the young: a nationwide study.

PURPOSE: Patients with epilepsy are at increased risk of premature death from all causes and likely also from sudden unexplained death (SUD). Many patients with epilepsy have significant comorbidity, and it is unclear how much of the increased risk can be explained by epilepsy itself. We aimed to chart the incidence of sudden unexpected death in epilepsy (SUDEP) and estimate the risk of death from all causes and SUD conferred by epilepsy independently. METHODS: We conducted a historical cohort study using data from Danish registries and a complete manual review of all death certificates. The population studied consisted of all Danish residents in the age group 1-35 years, in the period 2000-2006 (inclusive), and the main outcome measures were risk of death and SUD. KEY FINDINGS: We identified 33,022 subjects with epilepsy (median follow-up 3.7 years) and 3,001,952 subjects without (median follow-up 7.0 years). Among 685 deaths in the population with epilepsy, we identified 50 cases of definite and probable SUDEP corresponding to an incidence rate of 41.1 (95% confidence interval [CI] 31.6-54.9) per 100,000 person-years. Incidence rates increased with age from 17.6 (95% CI 9.5-32.8) in the age group 1-18 years to 73.8 (95% CI 52.5-103.8) for the age group 24-35 years. Having epilepsy increased the crude risk of death with a hazard ratio (HR) of 11.9 (95% CI 11.0-12.9). When adjusting for sex and comorbidities often encountered in patients with epilepsy (neurologic disease including cerebral palsy, psychiatric disease including mental retardation, and congenital disorders), as well as the Charlson comorbidity score, the HR fell to 5.4 (95% CI 4.9-6.0). The crude HR for SUD was 27.5 (95% CI 18.1-41.8) and fell to 16.3 (95% CI 9.8-26.9) when adjusted for the same covariates as above. SIGNIFICANCE: Epilepsy in and of itself carries a significant risk of premature death and SUD. These findings highlight the potential gains of risk factor modification for the prevention of premature death and SUDEP in patients with epilepsy.

Prior myocardial infarction in the young: predisposes to a high relative risk but low absolute risk of a sudden cardiac death.

AIMS: The study reports the relative and absolute risk of sudden cardiac death (SCD) in patients <36 years with prior myocardial infarction (MI). METHODS AND RESULTS: Through review of death certificates, we identified all SCDs in Danes aged 18-35 years between 1 January 2000 until 31st December 2006. We then used the unique Danish civil registration number, which enabled us to follow all Danes in national registries, in the same period. Through the National Patient Registry we identified those with a prior myocardial infarction [implantable cardioverter defibrillator (ICD)-8: 410, ICD-10: I21 and I22] and incidence rates for SCD were estimated for survivors of MI and for individuals who had not yet suffered an MI, respectively. We estimated the relative risk of SCD and all-cause mortality by using extended Cox regression models. The 1,862,431 Danes aged between 18 and 35 years were followed in 9,388,453 person-years between 2000 and 2006. There were 7434 deaths of which 387 (5.2%) were SCDs. Myocardial infarction was diagnosed in 1234 patients, of those 10 died of SCD. Prior MI increased the incidence rate of SCD from 4.1 to 305.0 per 100,000 person-years [95% confidence interval (CI): 164.1-567.0]. Myocardial infarction was correlated with SCD and all-cause mortality, with a hazard ratio (HR) of 55.5 (95% CI: 29.5-104.4), P< 0.0001 and HR 8.3 (95% CI: 6.0-11.3), P< 0.0001, respectively. CONCLUSION: We report that prior MI at a young age significantly increases SCD incidence from 4.1 to 305.0 per 100,000 person-years. Myocardial infarction is furthermore correlated with SCD and all-cause mortality with HR of 55.5 and 8.3, respectively.

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

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

Waiting for a pacemaker: is it dangerous?

AIMS: To determine waiting period-related morbidity, mortality, and adverse events in acute patients waiting for a permanent pacemaker (PPM). METHODS AND RESULTS: A retrospective chart review of all PPM implantations in Region Zealand, Denmark, in 2009 was conducted. Patients were excluded if they were discharged from the hospital during the waiting period or referred from the outpatient department. Adverse events were tracked. Four hundred and eighty-seven PPM implantations were identified. Of these, 259 patients (53.2%) required acute PPM implantation and waited a mean of 5.1 days from PPM indication to implantation. A lack of implantation capacity was responsible for 4.5 of the waiting days. Twenty-nine patients (11.2%) developed infection while waiting, primarily urinary tract infections. Thirteen patients (5.0%) suffered non-sustained ventricular tachycardia, and eight patients (3.1%) suffered clinical cardiac arrest followed by successful resuscitation. Three patients (1.2%) died during the waiting period before successful implantation. Forty-eight patients (18.5%) received the sympathomimetic beta-adrenergic agent, isoprenaline, and seven patients (13.7%) had malignant arrhythmias or cardiac arrest, reaching statistical significance (P < 0.05). Twenty-eight patients (10.8%) had a temporary transvenous-pacing catheter applied acutely. CONCLUSIONS: The patients awaited acute PPM implantations for a mean of 4.5 days because of capacity problems. Overall, 83 patients (32.0%) experienced at least one adverse event during the waiting period. The present study indicates that a waiting period is dangerous as it is associated with an increased risk of adverse events. Acute PPMs should be implanted with a 24-h pacemaker implantation service capacity.