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

Abstract 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\u201335 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 \u2009=\u20090.02) and died less often in a public place (16 vs. 26%, p \u2009=\u20090.01). 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\u20132.4), p \u2009<\u20090.01). 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

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.This work was supported by the Novo Nordisk Foundation, Copenhagen, Denmark [NNFOC140011573]. JS, reciewed salary from the Department of Forensic Medicine, Univiserty of Copenhagen

A Novel SCN5A Mutation in a Patient with Coexistence of Brugada Syndrome Traits and Ischaemic Heart Disease

Brugada syndrome (BrS) is a primary electrical heart disease, which can lead to sudden cardiac death. In older patients with BrS, the disease may coexist with ischaemic heart disease (IHD) and recent studies support a synergistic proarrhythmic effect of the two disease entities. We report a case that illustrates this. The index patient was a middle-aged patient with BrS traits, IHD, and aborted sudden cardiac death. Mutation analysis discovered a novel mutation P468L in the NaV1.5 sodium channel. Surprisingly, voltage-clamp experiments on the wild-type and mutant NaV1.5 channels expressed in HEK cells revealed no functional effect of the mutation. In a patient like ours, the distinction between IHD and BrS as the cause of an aborted sudden cardiac death is hard to establish and mounting evidence shows that coexistence of the two may have a synergistic proarrhythmic effect

Oxygen conserving mitochondrial adaptations in the skeletal muscles of breath hold divers

BackgroundThe performance of elite breath hold divers (BHD) includes static breath hold for more than 11 minutes, swimming as far as 300 m, or going below 250 m in depth, all on a single breath of air. Diving mammals are adapted to sustain oxidative metabolism in hypoxic conditions through several metabolic adaptations, including improved capacity for oxygen transport and mitochondrial oxidative phosphorylation in skeletal muscle. It was hypothesized that similar adaptations characterized human BHD. Hence, the purpose of this study was to examine the capacity for oxidative metabolism in skeletal muscle of BHD compared to matched controls.MethodsBiopsies were obtained from the lateral vastus of the femoral muscle from 8 Danish BHD and 8 non-diving controls (Judo athletes) matched for morphometry and whole body VO2max. High resolution respirometry was used to determine mitochondrial respiratory capacity and leak respiration with simultaneous measurement of mitochondrial H2O2 emission. Maximal citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HAD) activity were measured in muscle tissue homogenates. Western Blotting was used to determine protein contents of respiratory complex I-V subunits and myoglobin in muscle tissue lysates.ResultsMuscle biopsies of BHD revealed lower mitochondrial leak respiration and electron transfer system (ETS) capacity and higher H2O2 emission during leak respiration than controls, with no differences in enzyme activities (CS and HAD) or protein content of mitochondrial complex subunits myoglobin, myosin heavy chain isoforms, markers of glucose metabolism and antioxidant enzymes.ConclusionWe demonstrated for the first time in humans, that the skeletal muscles of BHD are characterized by lower mitochondrial oxygen consumption both during low leak and high (ETS) respiration than matched controls. This supports previous observations of diving mammals demonstrating a lower aerobic mitochondrial capacity of the skeletal muscles as an oxygen conserving adaptation during prolonged dives.</div

Canine specific ELISA for coagulation factor VII

Canine coagulation factor VII (FVII) deficiency can be hereditary or acquired and may cause life threatening bleeding episodes if untreated. FVII procoagulant activity can be measured by FVII activity (FVII:C), but assays for measurement of canine specific FVII antigen (FVII:Ag) have not been available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable in the diagnosis of hereditary canine FVII deficiency