High Incidence of Inappropriate Alarms in Patients with Wearable Cardioverter-Defibrillators: Findings from the Swiss WCD Registry.

BACKGROUND: The wearable cardioverter defibrillator (WCD) uses surface electrodes to detect arrhythmia before initiating a treatment sequence. However, it is also prone to inappropriate detection due to artefacts. OBJECTIVE: The aim of this study is to assess the alarm burden in patients and its impact on clinical outcomes. METHODS: Patients from the nationwide Swiss WCD Registry were included. Clinical characteristics and data were obtained from the WCDs. Arrhythmia recordings ≥30 s in length were analysed and categorized as VT/VF, atrial fibrillation (AF), supraventricular tachycardia (SVT) or artefact. RESULTS: A total of 10653 device alarms were documented in 324 of 456 patients (71.1%) over a mean WCD wear-time of 2.0 ± 1.6 months. Episode duration was 30 s or more in 2996 alarms (28.2%). One hundred and eleven (3.7%) were VT/VF episodes. The remaining recordings were inappropriate detections (2736 (91%) due to artefacts; 117 (3.7%) AF; 48 (1.6%) SVT). Two-hundred and seven patients (45%) had three or more alarms per month. Obesity was significantly associated with three or more alarms per month (p = 0.01, 27.7% vs. 15.9%). High alarm burden was not associated with a lower average daily wear time (20.8 h vs. 20.7 h, p = 0.785) or a decreased implantable cardioverter defibrillator implantation rate after stopping WCD use (48% vs. 47.3%, p = 0.156). CONCLUSIONS: In patients using WCDs, alarms emitted by the device and impending inappropriate shocks were frequent and most commonly caused by artefacts. A high alarm burden was associated with obesity but did not lead to a decreased adherence.

Use of the wearable cardioverter-defibrillator - the Swiss experience.

INTRODUCTION: Sudden cardiac death caused by malignant arrhythmia can be prevented by the use of defibrillators. Although the wearable cardioverter defibrillator (WCD) can prevent such an event, its role in clinical practice is ill defined. We investigated the use of the WCD in Switzerland with emphasis on prescription rate, therapy adherence and treatment rate. MATERIALS AND METHODS: The Swiss WCD Registry is a retrospective observational registry including patients using a WCD. Patients were included from the first WCD use in Switzerland until February 2018. Baseline characteristics and data on WCD usage were examined for the total study population, and separately for each hospital. RESULTS: From 1 December 2011 to 18 February 2018, a total of 456 patients (67.1% of all WCDs prescribed in Switzerland and 81.1% of all prescribed in the participating hospitals) were included in the registry. Up to 2017 there was a yearly increase in the number of prescribed WCDs to a maximum of 271 prescriptions per year. The mean age of patients was 57 years (± 14), 81 (17.8%) were female and mean left ventricular ejection fraction (EF) was 32% (± 13). The most common indications for WCD use were new-onset ischaemic cardiomyopathy (ICM) with EF ≤35% (206 patients, 45.2%), new-onset nonischaemic cardiomyopathy (NICM) with EF ≤35% (115 patients, 25.2%), unknown arrhythmic risk (83 patients, 18.2%), bridging to implantable cardioverter-defibrillator implantation or heart transplant (37 patients, 8.1%) and congenital/inherited heart disease (15 patients, 3.3%). Median wear duration was 58 days (interquartile range [IQR] 31–94) with a median average daily wear time of 22.6 hours (IQR 20–23.2). Seventeen appropriate therapies from the WCD were delivered in the whole population (treatment rate: 3.7%) to a total of 12 patients (2.6% of all patients). The most common underlying heart disease in patients with a treatment was ICM (13/17, 76.5%). There were no inappropriate treatments. CONCLUSION: The use of WCDs has increased in Switzerland over the years for a variety of indications. There is high therapy adherence to the WCD, and a treatment rate comparable to previously published registry data.  .

Loss of epithelium-specific GPx2 results in aberrant cell fate decisions during intestinal differentiation.

The selenoprotein glutathione peroxidase 2 (GPx2) is expressed in the epithelium of the gastrointestinal tract, where it is thought to be involved in maintaining mucosal homeostasis. To gain novel insights into the role of GPx2, proteomic profiles of colonic tissues either derived from wild type (WT) or GPx2 knockout (KO) mice, maintained under selenium (Se) deficiency or adequate Se supplementation conditions were established and analyzed. Amongst the panel of differentially expressed proteins, the calcium-activated chloride channel regulator 1 (CLCA1) was significantly down-regulated in GPx2 KO versus WT mice regardless of the given Se status. Moreover, transcript levels of the isoforms CLCA2 and CLCA3 showed a similar expression pattern. In the intestine, CLCA1 is usually restricted to mucin-producing goblet cells. However, although -SeKO mice had the highest numbers of goblet cells as confirmed by significantly enhanced mRNA expression levels of the goblet cell marker mucin-2, the observed expression pattern suggests that GPx2 KO goblet cells might be limited in synthesizing CLCA1. Furthermore, transcript levels of differentiation markers such as chromogranin-1 (Chga) for enteroendocrine cells and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) for stem cells were also downregulated in GPx2 KO mice. Moreover, this was accompanied by a downregulation of the mRNA expression levels of the intestinal hormones glucagon-like peptide 1 (Glp1), ghrelin (Ghrl) and somatostatin (Sst). Thus, it seems that GPx2 might be important for the modulation of cell fate decisions in the murine intestinal epithelium.

Altered protein expression pattern in colon tissue of mice upon supplementation with distinct selenium compounds.

The essential trace element selenium (Se) is controversially discussed concerning its role in health and disease. Its various physiological functions are largely mediated by Se incorporation in the catalytic center of selenoproteins. In order to gain insights into the impact of Se deficiency and of supplementation with different Se compounds (selenite, selenate, selenomethionine) at defined concentrations (recommended, 150 µg/kg diet; excessive, 750 µg/kg diet) in murine colon tissues, a 20-week feeding experiment was performed followed by analysis of the protein expression pattern of colon tissue specimens by 2D-DIGE and MALDI-TOF MS. Using this approach, 24 protein spots were identified to be significantly regulated by the different Se compounds. These included the antioxidant enzyme peroxiredoxin-5 (PRDX5), proteins with binding capabilities, such as cofilin-1 (COF1), calmodulin, and annexin A2 (ANXA2), and proteins involved in catalytic processes, such as 6-phosphogluconate dehydrogenase (6PGD). Furthermore, the Se compounds demonstrated a differential impact on the expression of the identified proteins. Selected target structures were validated by qPCR and Western blot which mainly confirmed the proteomic profiling data. Thus, novel Se-regulated proteins in colon tissues have been identified, which expand our understanding of the physiologic role of Se in colon tissue.

Individual effects of different selenocompounds on the hepatic proteome and energy metabolism of mice.

BACKGROUND: Selenium (Se) exerts its biological activity largely via selenoproteins, which are key enzymes for maintaining the cellular redox homeostasis. However, besides these beneficial effects there is also evidence that an oversupply of Se might increase the risk towards developing metabolic disorders. To address this in more detail, we directly compared effects of feeding distinct Se compounds and concentrations on hepatic metabolism and expression profiles of mice. METHODS: Male C57BL6/J mice received either a selenium-deficient diet or diets enriched with adequate or high doses of selenite, selenate or selenomethionine for 20weeks. Subsequently, metabolic parameters, enzymatic activities and expression levels of hepatic selenoproteins, Nrf2 targets, and additional redox-sensitive proteins were analyzed. Furthermore, 2D-DIGE-based proteomic profiling revealed Se compound-specific differentially expressed proteins. RESULTS: Whereas heterogeneous effects between high concentrations of the Se compounds were observed with regard to body weight and metabolic activities, selenoproteins were only marginally increased by high Se concentrations in comparison to the respective adequate feeding. In particular the high-SeMet group showed a unique response compromising higher hepatic Se levels in comparison to all other groups. Accordingly, hepatic glutathione (GSH) levels, glutathione S-transferase (GST) activity, and GSTpi1 expression were comparably high in the high-SeMet and Se-deficient group, indicating that compound-specific effects of high doses appear to be independent of selenoproteins. CONCLUSIONS: Not only the nature, but also the concentration of Se compounds differentially affect biological processes. GENERAL SIGNIFICANCE: Thus, it is important to consider Se compound-specific effects when supplementing with selenium.

Effects of selenium supplementation on selenium status of farmed fallow deer in outdoor pens.

The study investigated the effects of selenium (Se) supplementation on Se status in farmed fallow deer. Fallow deer were housed on grass pasture and adapted to consume ∼200 g of pelleted grain daily. Animals were divided into two groups. One group received pelleted grain enriched with sodium selenate for 12 weeks (Se+ group, N = 10). Se intake for the first 7 weeks was 0.18 mg/kg dry matter (DM) and 0.32 mg/kg DM for the subsequent 5 weeks. The control group was fed pelleted grain without extra Se (Se− group, N = 9, 0.06-0.08 mg/kg DM). Blood samples were collected at the beginning and the end of the experiment. After the animals were slaughtered, tissue samples were collected for analysis of Se concentrations and Se-dependent glutathione peroxidase 1 (GPx1) activity. In addition, Se-independent α-glutathione-S-transferase (α-GST) activity was analyzed in liver tissue. Se supplementation significantly increased Se levels in plasma and in tissues as follows: liver > spleen > skeletal muscle > myocardium > kidney. Se supplementation also significantly increased GPx1 activity in tissues in the following order: liver > skeletal muscle > spleen = myocardium > kidneys. However, hepatic α-GST activity did not differ between Se+ and Se− groups. As expected, Se supplementation increased blood and tissue Se concentrations and GPx1 activity, which suggests a better antioxidant status. However, the activity of α-GST, an important Se-independent antioxidant enzyme, was not altered, presumably because GPx provided an adequate antioxidant capacity even though Se intake was low.

Combining protein and carbohydrate increases postprandial insulin levels but does not improve glucose response in patients with type 2 diabetes.

OBJECTIVE: A combined load of carbohydrate and protein stimulates insulin secretion. However, results on postprandial glucose responses in type 2 diabetic (T2D) subjects have been inconclusive. Therefore, we investigated the effects of co-ingestion of carbohydrate and protein on glucose and insulin responses in these subjects. METHODS: After an overnight fast, 30 subjects consumed a drink containing 50 g of slowly-digested isomaltulose (ISO), combined either with a mixture of 21 g whey/soy (ISO+WS) or with 21 g casein (ISO+C) in a randomized order on separate days. In another experiment, the subjects consumed a control drink containing only 50 g ISO. RESULTS: No significant differences in glucose responses were observed after ingestion of the drinks. Compared to ingestion of ISO alone, insulin response was ~190%-270% higher (P<.001), whereas insulin action was lower (P<.01) after ingestion of ISO+WS and ISO+C. Plasma insulin levels increased more significantly (P<.001) after ingestion of ISO+WS compared to ISO+C and were positively correlated with total amino acid levels (P<.001). Insulin action, however, showed a greater decrease following ingestion of ISO+WS than ISO+C (P<.01). CONCLUSIONS: Combining carbohydrate with protein can elevate postprandial insulin levels, but decreases insulin action, and therefore does not improve glucose response in T2D subjects. Our results further suggest that different types of proteins (i.e., fast-absorbing whey/soy vs. slow-absorbing casein) differently modulate insulin response and insulin action. A fast-absorbing protein mixture reduces insulin action to a greater extent than a slow-absorbing protein, and therefore may not be recommended for glycemic control in T2D patients.

Effect of increasing selenite concentrations, vitamin E supplementation and different fetal calf serum content on GPx1 activity in primary cultured rabbit hepatocytes.

Primary rabbit hepatocytes from 6 week old female New Zealand White rabbits (3.0 x 10(6) viable hepatocytes per treatment) were incubated for 24 h or 48 h with two basic variants of the selenium and vitamin E free DMEM/F12-HAM nutrition medium containing 2.5% or 10% fetal calf serum (FCS). Selenium and vitamin E concentrations of the media were varied by the addition of 0, 10, 50 and 100 ng Se/mL medium as sodium selenite and 100 microg alpha-tocopheryl acetate/mL. Lactic dehydrogenase (LDH) leakage of the hepatocytes was not influenced by the various selenium concentrations of the media, whereas vitamin E addition significantly inhibited LDH release. The activity of cellular glutathione peroxidase (GPx1) was markedly induced by increasing the selenium supplementation of the culture media. Vitamin E supply further enhanced GPx1 induction. In hepatocytes cultivated at the lower serum concentration (2.5% FCS), increasing the selenite concentration of the media raised GPx1 and reduced the intracellular levels of the reduced tripeptide glutathione (GSH). No vectored relation between the selenium concentration of the media and the activity of superoxide dismutase (SOD) could be observed. After both incubation periods (24 h and 48 h) SOD activity was significantly higher in the cytosol of hepatocytes grown in media containing 10% FCS as compared to cells incubated at the 2.5% FCS level. Furthermore, SOD activity was reduced by the addition of vitamin E to the media. In conclusion the results indicate an effective metabolism of rabbit hepatocytes for selenite even in amounts as low as nanograms. A general cytoprotective role for vitamin E can be shown by its ability to decrease LDH leakage and by the reduction of SOD activity.

Parameters of dietary selenium and vitamin E deficiency in growing rabbits.

4 x 5 growing female rabbits (New Zealand White) with an initial live weight of 610 +/- 62 g were fed a torula yeast based semisynthetic diet low in selenium (<0.03 mg/kg diet) and containing <2 mg alpha-tocopherol per kg (group I). Group II received a vitamin E supplementation of 150 mg alpha-tocopherylacetate per kg diet, whereas for group III 0.40 mg Se as Na-selenite and for group IV both supplements were added. Selenium status and parameters of tissue damage were analyzed after 10 weeks on experiment (live weight 2,355 +/- 145 g). Selenium depletion of the Se deficient rabbits (groups I and II) was indicated by a significantly lower plasma Se content (group I: 38.3 +/- 6.23 microg Se/mL plasma, group II: 42.6 +/- 9.77, group III: 149 +/- 33.4, group IV: 126 +/- 6.45) and a significantly lower liver Se content (group I: 89.4 +/- 18.2 microg/kg fresh matter, group II: 111 +/- 26.2) as compared to the Se supplemented groups III (983 +/- 204) and IV (926 +/- 73.9). After 5 weeks on the experimental diets differences in the development of plasma glutathione peroxidase were observed. As compared to the initial status group (45.2 +/- 4.50) pGPx activity in mU/mg protein was decreased in group I (19.1 +/- 7.08), remained almost stable in the vitamin E supplemented group II (46.3 +/- 11.2) whereas an elevated enzyme activity was measured in the Se supplemented groups III (62.4 +/- 23.9) and IV (106 +/- 19.9). In the rabbit organs investigated 10 weeks of Se deficiency caused a significant loss of Se dependent cellular glutathione peroxidase activity (GPx1) of 94% (liver), 80% (kidney), 50% (heart muscle) and 60% (musculus longissimus dorsi) in comparison to Se supplemented control animals. Damage of cellular lipids and proteins in the liver was due to either Se or vitamin E deficiency. However damage was most severe under conditions of a combined Se and vitamin E deficiency. It can be concluded that the activity of plasma glutathione peroxidase is a sensitive indicator of Se deficiency in rabbits. The loss of GPx1 activity indicates the selenium depletion in various rabbit organs. Both selenium and vitamin E are essential and highly efficient antioxidants which protect rabbits against lipid and protein oxidation.