[Heart failure with reduced left ventricular ejection fraction (HFrEF, HFmrEF)].

INTRODUCTION: Heart failure is the final stage of most heart diseases and, with over 64 million people affected worldwide, is considered a global pandemic. The prevalence is expected to continue to rise. The prevention and treatment of cardiovascular diseases and the early detection of patients suffering from heart failure are essential. Different therapies are available depending on the extent of the reduction in left ventricular ejection fraction (LVEF). Optimal treatment prevents unnecessary admissions to hospital, reduces mortality and improves quality of life. In the following article, we discuss the diagnosis of heart failure and explain the various treatment options for heart failure with reduced LVEF (HFrEF, HFmrEF).

Mitigating the risk of flow deterioration by deferring stent optimization in STEMI patients with large thrombus burden: Insights from a prospective cohort study.

OBJECTIVES: It is uncertain, if omitting post-dilatation and stent oversizing (stent optimization) is safe and may decrease the risk for distal thrombus embolization (DTE) in STEMI patients with large thrombus burden (LTB). BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) with stenting, (DTE) and flow deterioration are common and increase infarct size leading to worse outcomes. METHODS: From a prospective registry, 74 consecutive STEMI patients with LTB undergoing pPCI with stenting and intentionally deferred stent optimization were analyzed. Imaging data and outcomes up to 2 years follow-up were analyzed. RESULTS: Overall, 74 patients (18% females) underwent deferred stent optimization. Direct stenting was performed in 13 (18%) patients. No major complications occurred during pPCI. Staged stent optimization was performed after a median of 4 (interquartile range (IQR) 3; 7) days. On optical coherence tomography, under-expansion and residual thrombus were present in 59 (80%) and 27 (36%) cases, respectively. During deferred stent optimization, we encountered no case of flow deterioration (slow or no-reflow) or side branch occlusion. Minimal lumen area (mm2) and stent expansion (%) were corrected from 4.87±1.86mm to 6.82±2.36mm (p<0.05) and from 69±18% to 91±12% (p<0.001), respectively. During follow-up, 1 patient (1.4%) required target lesion revascularization and 1 (1.4%) patient succumbed from cardiovascular death. CONCLUSIONS: Among STEMI patients with LTB, deferring stent optimization in the setting of pPCI appears safe and potentially mitigates the risk of DTE. The impact of this approach on infarct size and clinical outcomes warrants further investigation in a dedicated trial.

Do cardiopulmonary exercise tests predict summit success and acute mountain sickness? A prospective observational field study at extreme altitude.

OBJECTIVE: During a high-altitude expedition, the association of cardiopulmonary exercise testing (CPET) parameters with the risk of developing acute mountain sickness (AMS) and the chance of reaching the summit were investigated. METHODS: Thirty-nine subjects underwent maximal CPET at lowlands and during ascent to Mount Himlung Himal (7126 m) at 4844 m, before and after 12 days of acclimatisation, and at 6022 m. Daily records of Lake-Louise-Score (LLS) determined AMS. Participants were categorised as AMS+ if moderate to severe AMS occurred. RESULTS: Maximal oxygen uptake (V̇O2max) decreased by 40.5%±13.7% at 6022 m and improved after acclimatisation (all p<0.001). Ventilation at maximal exercise (VEmax) was reduced at 6022 m, but higher VEmax was related to summit success (p=0.031). In the 23 AMS+ subjects (mean LLS 7.4±2.4), a pronounced exercise-induced oxygen desaturation (ΔSpO2exercise) was found after arrival at 4844 m (p=0.005). ΔSpO2exercise >-14.0% identified 74% of participants correctly with a sensitivity of 70% and specificity of 81% for predicting moderate to severe AMS. All 15 summiteers showed higher V̇O2max (p<0.001), and a higher risk of AMS in non-summiteers was suggested but did not reach statistical significance (OR: 3.64 (95% CI: 0.78 to 17.58), p=0.057). V̇O2max ≥49.0 mL/min/kg at lowlands and ≥35.0 mL/min/kg at 4844 m predicted summit success with a sensitivity of 46.7% and 53.3%, and specificity of 83.3% and 91.3%, respectively. CONCLUSION: Summiteers were able to sustain higher VEmax throughout the expedition. Baseline V̇O2max below 49.0 mL/min/kg was associated with a high chance of 83.3% for summit failure, when climbing without supplemental oxygen. A pronounced drop of SpO2exercise at 4844 m may identify climbers at higher risk of AMS.

Self-imaging of tailored vortex pulse arrays and spectral Gouy rotation echoes.

Self-imaging of femtosecond pulses with orbital angular momentum is studied in spectral domain by illuminating the orthogonal arrays of spiral gratings. Spectral Gouy rotation, i.e., the characteristic circulation of extremal regions near phase singularities in spatial spectral maps, is found to partially reappear at discrete distances. The self-imaging of co-rotating and counter-rotating vortices is compared in intensity and spectral behavior. High-selectivity pattern recognition from weakly modulated spectral maps is demonstrated by analyzing spectral moments. By our experiments, the classical Talbot effect is extended to polychromatic pulsed vortex arrays with controlled maps of rotation sign.

Is Hyalella azteca a Suitable Model Leaf-Shredding Benthic Crustacean for Testing the Toxicity of Sediment-Associated Metals in Europe?

The leaf-shredding crustacean Hyalella azteca, which is indigenous to Northern and Central America, is used to assess environmental risks associated with (metal-)contaminated sediments and to propose sediment quality standards also in Europe. Yet, it is unknown if H. azteca is protective for European crustacean shredders. We thus compared the sensitivity of H. azteca with that of the European species Asellus aquaticus and Gammarus fossarum towards copper- and cadmium-contaminated sediments (prepared according to OECD 218) under laboratory conditions employing mortality and leaf consumption as endpoints. H. azteca either reacted approximately fourfold more sensitive than the most tolerant tested species (as for cadmium) or its sensitivity was only 1.6 times lower than the highest sensitivity determined (as for copper), which should be covered by safety factors applied during risk assessments. Therefore, the results for the sediment type and the two heavy metals tested during the present study in combination with the existence of standardized testing protocols, their ease of culture, and short generation time, suggest H. azteca as suitable crustacean model shredder for assessing the toxicity of sediment-associated metals in Europe.

Identification of Unknown Antiandrogenic Compounds in Surface Waters by Effect-Directed Analysis (EDA) Using a Parallel Fractionation Approach.

Among all the nuclear-receptor mediated endocrine disruptive effects, antiandrogenicity is frequently observed in aquatic environments and may pose a risk to aquatic organisms. Linking these effects to responsible chemicals is challenging and a great share of antiandrogenic activity detected in the environment has not been explained yet. To identify drivers of this effect at a hot spot of antiandrogenicity in the German river Holtemme, we applied effect-directed analysis (EDA) including a parallel fractionation approach, a downscaled luciferase reporter gene cell-based anti-AR-CALUX assay and LC-HRMS/MS nontarget screening. We identified and confirmed the highly potent antiandrogen 4-methyl-7-diethylaminocoumarin (C47) and two derivatives in the active fractions. The relative potency of C47 to the reference compound flutamide was over 5.2, whereas the derivatives were less potent. C47 was detected at a concentration of 13.7 µg/L, equal to 71.4 µg flutamide equivalents per liter (FEq/L) in the nonconcentrated water extract that was posing an antiandrogenic activity equal to 45.5 (±13.7 SD) FEq/L. Thus, C47 was quantitatively confirmed as the major cause of the measured effect in vitro. Finally, the antiandrogenic activity of C47 and one derivate was confirmed in vivo in spiggin-gfp Medaka. An endocrine disrupting effect of C47 was observed already at the concentration equal to the concentration in the nonconcentrated water extract, underlining the high risk posed by this compound to the aquatic ecosystem. This is of some concern since C47 is used in a number of consumer products indicating environmental as well as human exposure.

Toward Streamlined Identification of Dioxin-like Compounds in Environmental Samples through Integration of Suspension Bioassay.

Effect-directed analysis (EDA) is a powerful strategy to identify biologically active compounds in environmental samples. However, in current EDA studies, fractionation and handling procedures are laborious, consist of multiple evaporation steps, and thus bear the risk of contamination and decreased recoveries of the target compounds. The low resulting throughput has been one of the major bottlenecks of EDA. Here, we propose a high-throughput EDA (HT-EDA) work-flow combining reversed phase high-performance liquid chromatography fractionation of samples into 96-well microplates, followed by toxicity assessment in the micro-EROD bioassay with the wild-type rat hepatoma H4IIE cells, and chemical analysis of bioactive fractions. The approach was evaluated using single substances, binary mixtures, and extracts of sediment samples collected at the Three Gorges Reservoir, Yangtze River, China, as well as the rivers Rhine and Elbe, Germany. Selected bioactive fractions were analyzed by highly sensitive gas chromatography-atmospheric pressure laser ionization-time-of-flight-mass spectrometry. In addition, we optimized the work-flow by seeding previously adapted suspension-cultured H4IIE cells directly into the microplate used for fractionation, which makes any transfers of fractionated samples unnecessary. The proposed HT-EDA work-flow simplifies the procedure for wider application in ecotoxicology and environmental routine programs.

A sensitive biomarker for the detection of aquatic contamination based on behavioral assays using zebrafish larvae.

An effective biological early warning system for the detection of water contamination should employ undemanding species that rapidly react to the presence of contaminants in their environment. The demonstrated reaction should be comprehensible and unambiguously evidential of the contamination event. This study utilized 96h post fertilization zebrafish larvae and tested their behavioral response to acute exposure to low concentrations of cadmium chloride (CdCl2) (5.0, 2.5, 1.25, 0.625mg/L) and permethrin (0.05, 0.029, 0.017, 0.01µg/L). We hypothesize that the number of larvae that show advanced trajectories in a group corresponds with water contamination, as the latter triggers avoidance behavior in the organisms. The proportion of advanced trajectories in the control and treated groups during the first minute of darkness was designated as a segregation parameter. It was parametrized and a threshold value was set using one CdCl2 trial and then applied to the remaining CdCl2 and permethrin replicates. For all cases, the method allowed distinguishing between the control and treated groups within two cycles of light: dark. The calculated parameter was statistically significantly different between the treated and control groups, except for the lowest CdCl2 concentration (0.625mg/L) in one replicate. This proof-of-concept study shows the potential of the proposed methodology for utilization as part of a multispecies biomonitoring system.

Linking in Vitro Effects and Detected Organic Micropollutants in Surface Water Using Mixture-Toxicity Modeling.

Surface water can contain countless organic micropollutants, and targeted chemical analysis alone may only detect a small fraction of the chemicals present. Consequently, bioanalytical tools can be applied complementary to chemical analysis to detect the effects of complex chemical mixtures. In this study, bioassays indicative of activation of the aryl hydrocarbon receptor (AhR), activation of the pregnane X receptor (PXR), activation of the estrogen receptor (ER), adaptive stress responses to oxidative stress (Nrf2), genotoxicity (p53) and inflammation (NF-κB) and the fish embryo toxicity test were applied along with chemical analysis to water extracts from the Danube River. Mixture-toxicity modeling was applied to determine the contribution of detected chemicals to the biological effect. Effect concentrations for between 0 to 13 detected chemicals could be found in the literature for the different bioassays. Detected chemicals explained less than 0.2% of the biological effect in the PXR activation, adaptive stress response, and fish embryo toxicity assays, while five chemicals explained up to 80% of ER activation, and three chemicals explained up to 71% of AhR activation. This study highlights the importance of fingerprinting the effects of detected chemicals.

Oxidative stress related effect of xenobiotics on eukaryotic model organism, Saccharomyces cerevisiae.

Ecotoxicological assays have traditionally focused on the effects of chemicals at the individual level by exploiting mortality and reproduction as endpoints. Although these two parameters are ecologically relevant, they rarely provide information regarding the elemental toxic mechanisms. Obviously, the number of xenobiotics used has been rapidly increased. Thus, any established measurement that shortens the actual outcome and, simultaneously provides information about toxic mechanisms is desirable. This research focused on the study of oxidative stress response as a biomarker in the eukaryotic model organism, Saccharomyces cerevisiae. For this, yeast cells were exposed to a set of selected environmentally relevant chemicals via different approaches, including cellular diagnostics, gene expression analysis and chemo-genetic screening. The results demonstrated that at the cellular level, model organisms reacted to different chemicals in distinct manner. For each xenobiotic, the correlation between toxic response of molecular and cellular levels are presented. Namely, the expression of target genes after chemical exposure affected the cellular alteration as evidenced by an elevated level of superoxide dismutase and a reduced amount of glutathione. Furthermore, the results derived from chemo-genetic screening, in which mutants lacking of gene of interest were employed, exhibited more susceptibility to test chemicals in comparison to the wildtype. The response of oxidative stress upon chemical exposure in budding yeast from this study is potentially useful for an establishment of a proper bio-test system which can eventually be linked to adverse effects at an individual level in higher eukaryotes.

Limited waterborne acute toxicity of native polycyclic aromatic compounds from coals of different types compared to their total hazard potential.

Coals contain native polycyclic aromatic compounds (PACs), which include polycyclic aromatic hydrocarbons (PAHs), and heterocyclic aromatic compounds (NSO-PACs) in considerably varying amounts up to 2500 mg/kg. Whereas PAC bioavailability and toxicity from coals are generally considered to be low, few studies have considered potential variations arising from the composition of different coal types including native PAC content. In the present study, fine particles of different coal types exhibiting variable properties were systematically investigated regarding their PAC bioavailability. PAH content reached up to 79 mg/kg EPA-PAH and 865 mg/kg total PAH. Determination of the toxic potential of extracted PACs in bioassays showed inhibition of Caenorhabditis elegans reproduction (up to 94%) and increased mortality of Danio rerio embryos (up to 100%) after exposure to extracts from lignite, sub-bituminous, and bituminous coals. Anthracite extracts showed no effects. Contact assays using whole coal samples revealed no toxicity to D. rerio embryos in any of the coal samples, suggesting low bioavailability of PACs. In contrast, C. elegans reproduction was inhibited by direct coal contact; however, the observed toxicity probably resulted from other coal effects. The results suggest that despite the high toxic potential of PACs present, their bioavailability from different coal types is very limited and independent of coal properties and native PAH content.

Application of equilibrium passive sampling to assess the influence of anthropogenic activities and bioturbation on the distribution of hydrophobic organic chemicals in North Sea sediment cores.

The pollution state in the German Bight was investigated by determination of pollutant concentrations of sediment samples using equilibrium passive sampling. Polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAH) were determined in the pore water of North Sea sediment. The freely dissolved pore water concentration (Cfree) was measured applying Solid Phase Microextraction (SPME) by using PDMS-coated glass fibers. The obtained results show that the North Sea contamination level with the investigated pollutants is relatively low. However, the stations close to the sediment-dumping site were higher contaminated. A macrofauna analysis showed that bioturbation activities were mostly present in the upper sediment layers, but a direct bioturbation influence on the sediment concentration distribution could not be shown. Overall, the contamination load was below baseline toxicity, but considering that several other priority pollutants will also make a contribution to the baseline toxicity, it can be counted as relatively high.

Treatment of In-Stent Restenosis Using a Dedicated Super High-Pressure Balloon.

BACKGROUND: Treatment of in-stent restenosis (ISR) is challenging and treatment failure rate remains high. Correction of stent under-expansion and neointimal compression using the twin-layer OPN™ highly non-compliant balloon (NCB) at high pressure (>30 atm) may lead to increased luminal gain and thus better clinical outcomes. We evaluated periprocedural safety and clinical long-term outcomes after ISR treatment using the OPN™ NCB in a real-world population. METHODS: From an ongoing registry, consecutive ISR patients treated with the OPN™ NCB at a tertiary cardiology center in Switzerland were analyzed. We evaluated procedural efficacy, periprocedural complications, target lesion/vessel failure (TLF/TVF), and major adverse cardiovascular events (MACE). RESULTS: Totally, 208 ISR lesions were treated in 188 patients (mean age 68 ± 13 years, 78 % males). Most lesions were moderately to heavily calcified (89 %), the majority (70.2 %) had complex lesion characteristics (AHA Type B2/C lesions) and 50.5 % were non-focal ISR lesions. After ISR treatment using high pressure pre- and post-dilatation (mean pressure 33 ± 6 atm) with the OPN™ NCB device, the rate of major complications was low (0.96 % coronary perforation, 4 % major dissections, 1.9 % no-reflow and 0.5 % acute vessel closure). At 1-year follow-up, MACE occurred in 19.7 %; 15.4 % patients had TVF; MI and stent thrombosis was found in 5.9 % and 2.1 % of all patients, respectively; and 5 patients died. CONCLUSIONS: For ISR treatment, using the super non-compliant OPN™ balloon at very high pressures is safe. Moreover, its use might lead to a low rate of TLF/TVF during long-term follow-up, but this requires further evaluation in dedicated comparative trials.

Trajectories of Cardiac Function Following Treatment With an Impella Device in Patients With Acute Anterior ST-Elevation Myocardial Infarction.

Background: Left ventricular (LV) unloading via the percutaneous micro-axial Impella pump is increasingly used in patients with anterior ST-segment elevation myocardial infarction (STEMI) and overt cardiogenic shock. In this context, the evolution of cardiac function and dimensions beyond hospital discharge remains uncertain. We aimed to characterize echocardiographic changes over time in patients with acute anterior STEMI treated with an Impella device. Methods: From an ongoing prospective registry, consecutive patients with acute anterior STEMI managed with an Impella device were extracted. Transthoracic echocardiography was performed at index hospitalization and at first outpatient follow-up. Predictors of response, defined as a ≥ 10% absolute increase in left ventricular ejection fraction (LVEF) at follow-up, were sought. Results: A total of 66 patients (89.4% male, aged 64.3 ± 11.6 years) with anterior STEMI were treated with an Impella device in the first 24 hours of hospitalization, from 2014 to 2022. In-hospital mortality was 24%. Major bleeding and vascular complications requiring surgery occurred in 24% and 11% of patients, respectively. At baseline, mean LVEF was 34% ±12%. At follow-up, survivors showed a significant increase in LVEF (P < 0.0001), whereas LV dimensions, diastolic parameters, and measures of right ventricular dimension and function remained stable. Overall, 28 patients had a ≥ 10% absolute increase in LVEF at follow-up. Baseline creatinine was the only significant predictor of response at univariate analysis. Conclusions: Among patients with anterior STEMI requiring mechanical hemodynamic support with an Impella device, the majority of survivors showed a sustained increase in LV function, without evidence of adverse remodelling. This signal warrants further investigation in dedicated trials.

Contexte: La décharge du ventricule gauche (VG) à l'aide de la pompe microaxiale percutanée Impella est de plus en plus employée chez les patients qui présentent un infarctus du myocarde avec élévation du segment ST (STEMI) et un choc cardiogénique manifeste. Dans ce contexte, l'évolution de la fonction et des dimensions cardiaques après le congé de l'hôpital demeure incertaine. Nous avons cherché à caractériser les variations des paramètres échocardiographiques au fil du temps chez les patients ayant subi un STEMI antérieur aigu traités au moyen d'un dispositif Impella. Méthodologie: À partir d'un registre prospectif actif, nous avons extrait les dossiers de patients consécutifs ayant subi un STEMI antérieur aigu et pris en charge au moyen d'un dispositif Impella. Une échocardiographie transthoracique a été effectuée durant l'hospitalisation de référence puis à la première visite de suivi ambulatoire. Les facteurs prédictifs de la réponse, définis comme une augmentation absolue ≥ 10 % de la fraction d'éjection ventriculaire gauche (FEVG) au moment du suivi, ont été recherchés. Résultats: Au total, 66 patients (89,4 % d'hommes, âgés de 64,3 ± 11,6 ans) ayant subi un STEMI antérieur ont été traités au moyen d'un dispositif Impella pendant les 24 premières heures de l'hospitalisation, entre 2014 et 2022. Le taux de mortalité hospitalière était de 24 %. Des hémorragies majeures et des complications vasculaires ayant nécessité une intervention chirurgicale sont survenues chez 24 % et 11 % des patients, respectivement. Au début de l'étude, la FEVG moyenne était de 34 % ± 12 %. Lors du suivi, les survivants affichaient une augmentation significative de la FEVG (p < 0,0001), alors que les dimensions du VG, les paramètres diastoliques et les mesures de la taille et de la fonction du ventricule droit étaient demeurés stables. Globalement, 28 patients affichaient une augmentation absolue de la FEVG ≥ 10 % lors du suivi. D'après l'analyse univariée, la créatininémie initiale était le seul facteur prédictif important de la réponse. Conclusions: Parmi les patients ayant subi un STEMI antérieur nécessitant un support mécanique hémodynamique au moyen d'un dispositif Impella, une augmentation durable de la fonction ventriculaire gauche, sans signe de remodelage indésirable, a été observée chez la majorité des survivants. Ce signal justifie une évaluation plus approfondie dans le cadre d'essais cliniques conçus à cet effet.

Direct Oral Anticoagulants Versus Vitamin K Antagonists for the Treatment of Left Ventricular Thrombi-Insights from a Swiss Multicenter Registry.

Current guidelines recommend vitamin K antagonists (VKAs) for the treatment of a left ventricular thrombus (LVT). However, direct oral anticoagulants (DOACs) show superior safety and efficacy compared with VKAs in most thromboembolic disorders. Nevertheless, DOACs remain poorly investigated for the treatment of LVT. To describe the thrombus resolution rate and clinical efficacy of DOACs versus VKAs in patients with LVT, we analyzed consecutive patients with confirmed LVT from a multicenter echocardiography database. Echocardiograms and clinical end points were evaluated independently. The thrombus resolution rate and clinical outcomes were compared according to the underlying anticoagulation regimen. In total, 101 patients were included (17.8% women, mean age 63.3 ± 13.2 years), 50.5% had recently experienced a myocardial infarction. The mean left ventricular ejection fraction was 36.6 ± 12.2%. DOACs versus VKAs were used in 48 and 53 patients, respectively. The median follow-up was 26.6 (interquartile range 11.8;41.2) months. Among patients receiving VKAs compared with DOACs, the thrombus resolved more rapidly within the first month in those taking VKAs (p = 0.049). No differences were seen between the 2 groups with respect to major bleedings, strokes, and other thromboembolic events. In each group, LVT recurred in 3 of the subjects (a total of 6) after discontinuation of anticoagulation. In conclusion, DOACs appear to be a safe and effective alternative to VKAs for the treatment of LVTs, but the rate of thrombus dissolution within 1 month after initiation of anticoagulation appears to be higher with VKAs. A sufficiently powered randomized trial is required to definitively define the role of DOACs in the treatment of LVT.

Highly precise micro-retroreflector array fabricated by the LIGA process and its application as tapped delay line filter.

We report on the fabrication of a one-dimensional micro-retroreflector array with a pitch of 100 µm. The array was fabricated by x-ray lithography and the lithographie, galvanik und abformung (LIGA) process in a 1 mm thick poly(methyl methacrylate) (PMMA) layer and subsequently covered with Au. The area of the array is 1 mm×10 mm. The high precision of the LIGA-based fabrication process allows one to use the element in spectrometers. Here, it is suggested to apply it to the implementation of a transversal filter for femtosecond pulses. We present a theoretical description of the performance of the retroreflector array as a filtering device and show experimental results.

Early Experience with the Biotronik Protego ICD Lead.

Background: In the last decade, newer generation ICD leads have been developed based on mechanistic insides of priorly failing leads. The aim of our study was to assess the long-term performance and mechanisms of failure of the 2013-introduced Biotronik Protego ICD lead in a real-world population. Methods: All patients, who underwent implantation of a Protego ICD lead at the Heart Centre Lucerne (Lucerne, Switzerland) between November 2013 and March 2017, were followed up with semi-annual device-controls. The primary endpoint was defined as lead failure, secondary endpoints compromised all-cause death, (in)appropriate shocks and the need for reintervention. Results: A total of 64 patients (mean age 66.7 ± 8.7 years, 30% female) underwent implantation of a Protego ICD lead: 78% for primary prevention, 53% had underlying ischemic heart disease, and 40.6% had a dilated cardiomyopathy (DCM). Mean left ventricular ejection fraction (LVEF) was 32.6 ± 10.5%. A total of 24 patients were treated with cardiac resynchronization therapy (CRT), and their baseline LVEF improved from 27.8 ± 7.3% before to 39.8 ± 12.5 after implantation (p < 0.001). Mean time to follow-up was 5.5 ± 0.9 years. Overall, 14 patients (26.6%) suffered from at least one episode of sustained ventricular tachycardia; in total 10 patients (15.6%) died. Two patients experienced lead failure due to lead fracture after 5.5 and 5.7 years, which was clinically apparent by an abrupt rise in lead impedance (>2000 Ω) and by repetitive inappropriate shocks, respectively. Conclusions: In this retrospective observational study, the calculated annual lead failure rate of the Biotronik Protego ICD lead was 0.59% per patient­thus, the durability and long-term performance seem to be promising.

Spatial and temporal variations in anti-androgenic activity and environmental risk in a small river.

The biological effects of multiple compounds have been widely investigated in aquatic environments. However, investigations of spatial and temporal variations in biological effects are rarely performed because they are time-consuming and labor-intensive. In this study, the variability of the anti-androgen, receptor-mediated activity of surface water samples was observed over 3 years using in vitro bioassays. Large-volume water samples were collected at one site upstream (Wer site) and two sites downstream (Sil and Nien sites) of a wastewater treatment plant (WWTP) outfall in the Holtemme River. Anti-AR activity was persistently present in all surface water samples over the three years. Large spatial variations in anti-androgenic activity were observed, with the lowest activity at the Wer site (mean concentration of 9.5 ± 7.2 µg flutamide equivalents/L) and the highest activity at the Sil site (mean concentration of 31.1 ± 12.0 µg flutamide equivalents/L) directly influenced by WWTP effluents. On the temporal scale, no distinct trend for anti-AR activity was observed among the seasons in all three years. The anti-androgenic activity at the upstream Wer site showed a decreasing trend from 2014 to 2016, indicating improved water quality. A novel bioanalytical-equivalent-based risk assessment method considering the frequency of risk occurrence was developed and then utilized to assess the environmental risk of anti-androgenic activity in the Holtemme River. The results revealed that the highest risk was present at the Sil site, while the risk was considerably reduced at the Nien site. The risk at the upstream Wer site was the lowest.

Long-Term Outcomes After Implantation of Magnesium-Based Bioresorbable Scaffolds-Insights From an All-Comer Registry.

Background: The magnesium-based sirolimus-eluting bioresorbable scaffold (Mg-BRS) Magmaris™ showed promising clinical outcomes, including low rates of both the target lesion failure (TLF) and scaffold thrombosis (ScT), in selected study patients. However, insights regarding long-term outcomes (>2 years) in all-comer populations remain scarce. Methods: We analyzed data from a single-center registry, including patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS), who had undergone percutaneous coronary intervention (PCI) using the Mg-BRS. The primary outcome comprised the device-oriented composite endpoint (DoCE) representing a hierarchical composite of cardiac death, ScT, target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR) up to 5 years. Results: In total, 84 patients [mean age 62 ± 11 years and 63 (75%) men] were treated with the Mg-BRS devices between June 2016 and March 2017. Overall, 101 lesions had successfully been treated with the Mg-BRS devices using 1.2 ± 0.4 devices per lesion. Pre- and postdilatation using dedicated devices had been performed in 101 (100%) and 98 (97%) of all the cases, respectively. After a median follow-up time of 62 (61-64) months, 14 (18%) patients had experienced DoCEs, whereas ScT was encountered in 4 (4.9%) patients [early ScTs (<30 days) in three cases and two fatal cases]. In 4 (29%) of DoCE cases, optical coherence tomography confirmed the Mg-BRS collapse and uncontrolled dismantling. Conclusion: In contradiction to earlier studies, we encountered a relatively high rate of DoCEs in an all-comer cohort treated with the Mg-BRS. We even observed scaffold collapse and uncontrolled dismantling. This implicates that this metal-based BRS requires further investigation and may only be used in highly selected cases.

Manual compression versus MANTA device for access management after impella removal on the ICU.

To compare the safety and efficacy of manual compression versus use of the MANTA closure device for access management after Impella removal on the intensive care unit (ICU). The number of patients treated with percutaneous left ventricular assist devices (pLVAD), namely Impella and ECMO, for complex cardiac procedures or shock, is growing. However, removal of pLVAD and large bore arteriotomy closure among such patients on the ICU remains challenging, since it is associated with a high risk for bleeding and vascular complications. Patients included in a prospective registry between 2017 and 2020 were analyzed. Bleeding and vascular access site complications were assessed and adjudicated according to VARC-2 criteria. We analyzed a cohort of 87 consecutive patients, who underwent access closure after Impella removal on ICU by using either the MANTA device or manual compression. The cohort´s mean age was 66.1 ± 10.7 years and 76 patients (87%) were recovering from CS. Mean support time was 40 h (interquartile range 24-69 h). MANTA was used in 31 patients (35.6%) and manual compression was applied in 56 patients (64.4%). Overall access related bleedings were significantly lower in the MANTA group (6.5% versus 39.3% (odds ratio (OR) 0.10, 95% CI 0.01-0.50; p = 0.001), and there was no significant difference in vascular complications between the two groups (p = 0.55). Our data suggests that the application of the MANTA device directly on the ICU is safe. In addition, it seems to reduce access related bleeding without increasing the risk of vascular complications.