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Today’s society is undergoing a paradigm shift driven by the megatrend of sustainability. This undeniably affects all areas of Western life. This paper aims to find out how the luxury industry is dealing with this change and what adjustments are made by the companies. For this purpose, interviews were conducted with managers from the luxury industry, in which they were asked about specific measures taken by their companies as well as trends in the industry. In a subsequent evaluation, the trends in the luxury industry were summarized for the areas of ecological, social, and economic sustainability. It was found that the area of environmental sustainability is significantly more focused than the other sub-areas. Furthermore, the need for a customer survey to validate the industry-based measures was identified.

Radiofrequency (RF) ablation is a commonly used method of atrial fibrillation (AF) treatment. High-power short-duration (HPSD) ablation has been suggested as a method to reduce procedure times whilst creating safe and lasting lesions. High-power ablation with contact force (CF)-sensing technology catheters might aid in a further improvement of safety whilst generating lasting transmural lesions.We report our experience using lesion size index (LSI)-guided 50 W ablation with a CF-sensing catheter of AF.We performed LSI-guided 50 W point-by-point ablation using a CF-sensing catheter (TactiCath). Target LSI at the anterior left atrium (LA) was 5.0 and at the posterior LA it was 4.5.Altogether, 4641 RF lesions were created in 86 consecutive patients. To reach a mean LSI of 4.9 ±0.01, a mean RF ablation time of 14.3 ±0.1 s was applied with a mean CF of 13.4 ±0.1 g. The RF time per lesion at the anterior wall of LA was 15.9 ±0.2 s, while it was 13 ±0.2 s at the posterior wall of LA. We observed force time integral (FTI) values between 36 g and 310 g. Procedure duration was 107 ±4 min with a RF ablation time of 15.4 ±0.6 min. No audible steam pops occurred. No pericardial effusion was observed. After a 1-year follow-up, no adverse events were reported and 83% of patients had no symptomatic arrhythmia recurrence.We provide evidence for the safety and efficacy of LSI-guided 50 W ablation using the TactiCath CF-sensing ablation catheter. These data support the use of high-power ablation with CF sensing technology to improve both safety and efficacy.

Rhythm interpretation of EGMs recorded by implantable loop recorders (ILRs) is facilitated in cases when p-waves are visible. The three most commonly used ILRs (BioMonitor III, Confirm RX and Reveal Linq) vary in size, electrode placement and filter algorithms. Therefore, p-wave visibility and amplitude on EGM may vary according to the implanted device.Consecutive patients were included after ILR implantation. P-wave visibility and amplitude were evaluated in sinus rhythm on 30-s EGMs with standard resolution (25 mm/mV for Biotronik and St. Jude, 30 mm/mV for Medtronic) and after maximum magnification. Additionally, baseline characteristics and p-wave amplitude in lead II on the surface-ECG were documented.148 patients with either BioMonitor III (n = 48), Confirm Rx (n = 51) or Reveal Linq (n = 49) ILRs were included. With standard resolution, p-waves were visible in 40 patients (83%) implanted with BioMonitor III, 36 patients (71%) with Confirm Rx and in 35 patients (71%) with Reveal Linq ILRs (p = 0.267). After maximum magnification, p-waves could not be identified in 6 patients with Confirm Rx ILR (12%) and 1 patient in both BioMonitor III and Reveal Linq ILR (2%; p = 0.051). The Biomonitor III showed higher p-wave amplitudes compared to the Confirm Rx (0.050 mV (0.040-0.070) vs. 0.030 mV (0.020-0.040); p0.001) and the Reveal Linq ILR (0.050 mV (0.040-0.070) vs. 0.030 mV (0.020-0.040); p0.001).P-wave amplitudes were higher in patients with Biomonitor III. This did not lead to higher p-wave visibility compared to the Confirm RX ILR or the Reveal Linq ILR.

Rapid development of virtual and data acquisition technology makes Digital Twin Technology (DT) one of the fundamental areas of research, while DT is one of the most promissory developments for the achievement of Industry 4.0. 48% percent of organisations implementing the Internet of Things are already using DT or plan to use DT in 2020. The global market for DT is expected to grow by 38 percent annually, reaching $16 billion by 2023. In addition, the number of participating organisations using digital twins is expected to triple by 2022. DTs are characterised by the integration between physical and virtual spaces. The driving idea for DT is to develop, test and build our devices in a virtual environment. The objective of this paper is to study the impact of DT in the automotive industry on the new marketing logic. This paper outlines the current challenges and possible directions for the future DT in marketing. This paper will be helpful for managers in the industry to use the advantages and potentials of DT.

The following article deals with the basic principles of intercultural management and possible improvements in terms of cultural, ethnic and gender diversification. The results are exemplarily applied to a bank located in Germany. The aim of this paper is to find out to what extent intercultural management could improve the productivity of Relatos-Bank in dealing with foreign employees or employees with a different cultural background. To achieve this goal, the authors con-duct a literature research. The main sources of information are books, journal articles and internet sources. It becomes clear that especially the different perceptions of different generations have a potential for conflict, which can be counteracted by applying presented scientific models. Equalizing the salaries of female and male employees and equalizing the rights and distribution of power could also be the key to becoming an open-minded, dynamic and fair organization that is pre-pared for the rapidly changing environment in which it operates.

BACKGROUND: Patients with COVID-19 seem to be prone to the development of arrhythmias. The objective of this trial was to determine the characteristics, clinical significance and therapeutic consequences of these arrhythmias in COVID-19 patients requiring intensive care unit (ICU) treatment. METHODS AND RESULTS: A total of 113 consecutive patients (mean age 64.1 ± 14.3 years, 30 (26.5%) female) with positive PCR testing for SARS-CoV2 as well as radiographically confirmed pulmonary involvement admitted to the ICU from March to May 2020 were included and observed for a cumulative time of 2321 days. Fifty episodes of sustained atrial tachycardias, five episodes of sustained ventricular arrhythmias and thirty bradycardic events were documented. Sustained new onset atrial arrhythmias were associated with hemodynamic deterioration in 13 cases (35.1%). Patients with new onset atrial arrhythmias were older, showed higher levels of Hs-Troponin and NT-proBNP, and a more severe course of disease. The 5 ventricular arrhythmias (two ventricular tachycardias, two episodes of ventricular fibrillation, and one torsade de pointes tachycardia) were observed in 4 patients. All episodes could be terminated by immediate defibrillation/cardioversion. Five bradycardic events were associated with hemodynamic deterioration. Precipitating factors could be identified in 19 of 30 episodes (63.3%), no patient required cardiac pacing. Baseline characteristics were not significantly different between patients with or without bradycardic events. CONCLUSION: Relevant arrhythmias are common in severely ill ICU patients with COVID-19. They are associated with worse courses of disease and require specific treatment. This makes daily close monitoring of telemetric data mandatory in this patient group.

Background Recent case reports and small studies have reported activation of the magnet-sensitive switches in cardiovascular implantable electronic devices (CIED) by the new iPhone 12 series, initiating asynchronous pacing in pacemakers and suspension of anti-tachycardia therapies in ICDs. Objective and Methods We performed a prospective single-center observational study to quantify the risk of magnetic field interactions of the iPhone 12 with CIEDs. A representative model of each CIED series from all manufacturers was tested ex vivo. Incidence and minimum distance necessary for magnet mode triggering were analyzed in 164 CIED patients with either the front or the back of the phone facing the device. The magnetic field of the iPhone 12 was analyzed using a 3-axis hall probe. Results Ex vivo, magnetic interferences occurred in 84.6% with the back compared to 46.2% with the front of the iPhone 12 facing the CIED. In vivo, activation of the magnet-sensitive switch occurred in 30 CIED patients (18.3%; 21 pacemaker, 9 ICDs) when the iPhone 12 was placed in close proximity over the CIED pocket and the back of the phone was facing the skin. Multiple binary logistic regression analysis identified the implantation depth (95% confidence interval [CI], 0.02 to 0.24) as independent predictor of magnet-sensitive switch activation. Conclusion Magnetic field interactions occur only in close proximity, and with precise alignment of the iPhone 12 and CIEDs. It is important to advise CIED patients to not put the iPhone 12 directly on the skin above the CIED. Further recommendations are not necessary.

Atrial and ventricular arrhythmias significantly contribute to morbidity and mortality of patients with cardiac disease. Ablation of these arrhythmias has shown to improve clinical outcomes, yet targeted ablation strategies rely on proper mapping capabilities. In the present study, we compare different modes of high-resolution mapping in clinically relevant arrhythmias using HD grid.Using the Advisor™ HD Grid Mapping Catheter in either the standard, the wave (bipolar along spline and bipolar orthogonal) or the wave diagonal setting, low-voltage areas were determined. Low-voltage was defined as local electrograms with an amplitude0.5 mV (bipolar; atria/ventricle) or4 mV (unipolar; ventricle). Ultra high-density mapping in 47 patients with ventricular tachycardia, ventricular premature beats, atrial fibrillation and atrial tachycardia provided reliable information for the understanding of the arrhythmia mechanism resulting in safe ablation procedures. Regions of low voltage were significantly decreased by 14 ± 2% and 31 ± 3% with wave and wave diagonal settings as compared to standard settings, respectively.Substrate mapping and risk stratification relies on proper low voltage discrimination. Even though the Advisor™ HD Grid Mapping Catheter was safely used in all cases, the extent of low voltage areas was mapping-mode dependent.

Lipids represent a valuable target for metabolomic studies since altered lipid metabolism is known to drive the pathological changes in cardiovascular disease (CVD). Metabolomic technologies give us the ability to measure thousands of metabolites providing us with a metabolic fingerprint of individual patients. Metabolomic studies in humans have supported previous findings into the pathomechanisms of CVD, namely atherosclerosis, apoptosis, inflammation, oxidative stress, and insulin resistance. The most widely studied classes of lipid metabolite biomarkers in CVD are phospholipids, sphingolipids/ceramides, glycolipids, cholesterol esters, fatty acids, and acylcarnitines. Technological advancements have enabled novel strategies to discover individual biomarkers or panels that may aid in the diagnosis and prognosis of CVD, with sphingolipids/ceramides as the most promising class of biomarkers thus far. In this review, application of metabolomic profiling for biomarker discovery to aid in the diagnosis and prognosis of CVD as well as metabolic abnormalities in CVD will be discussed with particular emphasis on lipid metabolites.

Background Left atrial low voltage areas (LVA) are associated with increased recurrence rates of atrial fibrillation (AF) after catheter ablation and can be a potential ablation target during the procedure. Therefore, noninvasive prediction of the presence and the distribution of LVA may help physicians to predict ablation outcomes and to guide antiarrhythmic management. Material and methods Seventy-three consecutive patients with atrial fibrillation undergoing first time left atrial ablation for paroxysmal or persistent AF were enrolled. P-wave properties (amplitude and duration) were measured in all limb and precordial leads in pre-interventional sinus rhythm surface ECGs and correlated with total LVA size. LVA were detected via high density low voltage maps of the left atrium in sinus rhythm. LVA were then manually encircled, their total size was calculated and given as a percentage of the total LA surface area. Results A significant, inverse correlation with LVA size was shown for P-wave amplitude for leads I, II, aVR, aVF, V1, V4, V5 and V6. Additionally, a significant positive correlation between LVA size and P-wave duration was shown for leads V1, V2 and V3. As the strongest correlation was shown for the amplitude in lead I (R = −0.578), this lead was used to find a potential cutoff for LVA prediction. The best cut-off for a P-wave amplitude in lead I to predict severe scarring (defined as LVA size >35%, according to UTAH stadium IV) was 0.062 mV with an area-under-the receiver-operating-characteristic curve of 0.935, a sensitivity of 85% and a specificity of 88%. Conclusions P-wave duration and amplitude show significant correlations with LVA size and may be used as a noninvasive tool to predict severe scarring. Amplitudes in lead I smaller than 0.062 mV were found to be predictive of LVA >35%.

The Cardiac Lipid Panel (CLP) is a novel panel of metabolomic biomarkers that has previously shown to improve the diagnostic and prognostic value for CHF patients. Several prognostic scores have been developed for cardiovascular disease (CVD) risk, but their use is limited to specific populations and precision is still inadequate. We compared a risk score using the CLP plus NT-proBNP to three commonly used risk scores: The Seattle Heart Failure Model (SHFM), Framingham Risk Score (FRS), and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score. We included 280 elderly CHF patients from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial. Cox Regression and hierarchical cluster analysis was performed. Integrated area under the curves (IAUC) was used as criterium for comparison. The mean (SD) follow-up period was 81 (33) months, and 95 (34%) subjects met the primary endpoint. The IAUC for FRS was 0.53, SHFM 0.61, MAGGIC 0.68, and CLP 0.78. Subjects were partitioned into three risk clusters: low, moderate, high with the CLP score showing the best ability to group patients into their respective risk cluster. A risk score composed of a novel panel of metabolite biomarkers plus NT-proBNP outperformed other common prognostic scores in predicting 10-year cardiovascular death in elderly ambulatory CHF patients. This approach could improve the clinical risk assessment of CHF patients.

The presented paper gives an overview of the most important and most common theories and concepts from the economic field of organisational change and is also enriched with quantitative publication data, which underlines the relevance of the topic. In particular, the topic presented is interwoven in an interdisciplinary way with economic psychological models, which are underpinned within the models with content from leading scholars in the field. The pace of change in companies is accelerating, as is technological change in our society. Adaptations of the corporate structure, but also of management techniques and tasks, are therefore indispensable. This includes not only the right approaches to employee motivation, but also the correct use of intrinsic and extrinsic motivational factors. Based on the hypothesis put forward by the scientist and researcher Rollinson in his book “Organisational behaviour and analysis” that managers believe motivational resources are available at all times, socio-economic and economic psychological theories are contrasted here in order to critically examine this statement. In addition, a fictitious company was created as a model for this work in order to illustrate the effects of motivational deficits in practice. In this context, the theories presented are applied to concrete problems within the model and conclusions are drawn about their influence and applicability. This led to the conclusion that motivation is a very individual challenge for each employee, which requires adapted and personalised approaches. On the other hand, the recommendations for action for supervisors in the case of motivation deficits also cannot be answered in a blanket manner, but can only be solved with the help of professional, expert-supported processing due to the economic-psychological realities of motivation. Identifying, analysing and remedying individual employee motivation deficits is, according to the authors, a problem and a challenge of great importance, especially in the context of rapidly changing ecosystems in modern companies, as motivation also influences other factors such as individual productivity. The authors therefore conclude that good motivation through the individual and customised promotion and further training of employees is an important point for achieving important corporate goals in order to remain competitive on the one hand and to create a productive and pleasant working environment on the other.

Background Cardiac injury associated with cytokine release frequently occurs in SARS-CoV-2 mediated coronavirus disease (COVID19) and mortality is particularly high in these patients. The mechanistic role of the COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. Moreover, the role of anti-inflammatory therapy to mitigate cardiac dysfunction remains elusive. Aims and methods We investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPS-CM). In addition, we evaluated the therapeutic potential of the IL-1β antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy. Results Isolated rat ventricular cardiomyocytes were exposed to control or COVID19 serum from intensive care unit (ICU) patients with severe ARDS and impaired cardiac function (LVEF 41±5%; 1/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154±43 U/l). Rat cardiomyocytes showed an early increase of myofilament sensitivity, a decrease of Ca2+ transient amplitudes and altered baseline [Ca2+] upon exposure to patient serum. In addition, we used iPS-CM to explore the long-term effect of patient serum on cardiac electrical and mechanical function. In iPS-CM, spontaneous Ca2+ release events were more likely to occur upon incubation with COVID19 serum and nuclear as well as cytosolic Ca2+ release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca2+ release or Ca2+ signaling during excitation-contraction coupling, nor significantly influenced cellular automaticity. Conclusion Serum derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Canakinumab had no beneficial effect on cellular Ca2+ signaling during excitation-contraction coupling. The presented method utilizing iPS-CM and in-vitro Ca2+ imaging might serve as a novel tool for precision medicine. It allows to investigate cytokine related cardiac dysfunction and pharmacological approaches useful therein.

Aim Wearable cardioverter defibrillator (WCD, LifeVest, and Zoll) therapy has become a useful tool to bridge a temporarily increased risk for sudden cardiac death. However, despite extensive use, there is a lack of evidence whether patients with myocarditis and impaired LVEF may benefit from treatment with a WCD. Methods and results We conducted a single‐centre retrospective observational study analysing patients with a WCD prescribed between September 2015 and April 2020 at our institution. In total, 135 patients were provided with a WCD, amongst these 76 patients (mean age 48.9 ± 13.7 years; 84.2% male) for clinically suspected myocarditis. Based on the results of the endomyocardial biopsy and, where available cardiac magnetic resonance imaging, 39 patients (51.3%) were diagnosed with myocarditis and impaired LVEF and 37 patients (48.7%) with dilated cardiomyopathy (DCM) without evidence of cardiac inflammation. The main immunohistopathological myocarditis subtype was lymphocytic myocarditis in 36 (92.3%) patients, and four patients (10.3%) of this group had an acute myocarditis. Three patients had cardiac sarcoidosis (7.7%). Ventricular tachycardia occurred in seven myocarditis (in total 41 VTs; 85.4% non‐sustained) and one DCM patients (in total one non‐sustained ventricular tachycardia). Calculated necessary WCD wearing time until ventricular tachycardia occurrence is 86.41 days in myocarditis compared with 6.46 years in DCM patients. Conclusions Our data suggest that myocarditis patients may benefit from WCD therapy. However, as our study is not powered for outcome, further randomized studies powered for the outcome morbidity and mortality are necessary.

The current classification of heart failure (HF) based on left ventricular (LV) ejection fraction (EF) identifies a large group of patients with preserved ejection fraction (HFpEF) with significant morbidity and mortality but without prognostic benefit from current HF therapy. Co-morbidities and conditions such as arterial hypertension, diabetes mellitus, chronic kidney disease, adiposity and aging shape the clinical phenotype and contribute to mortality. LV diastolic dysfunction and LV structural remodeling are hallmarks of HFpEF, and are linked to remodeling of the cardiomyocyte and extracellular matrix. Pulmonary hypertension (PH) and right ventricular dysfunction (RVD) are particularly common in HFpEF, and mortality is up to 10-fold higher in HFpEF patients with vs. without RV dysfunction. Here, we review alterations in cardiomyocyte function (i.e., ion homeostasis, sarcomere function and cellular metabolism) associated with diastolic dysfunction and summarize the main underlying cellular pathways. The contribution and interaction of systemic and regional upstream signaling such as chronic inflammation, neurohumoral activation, and NO-cGMP-related pathways are outlined in detail, and their diagnostic and therapeutic potential is discussed in the context of preclinical and clinical studies. In addition, we summarize prevalence and pathomechanisms of RV dysfunction in the context of HFpEF and discuss mechanisms connecting LV and RV dysfunction in HFpEF. Dissecting the molecular mechanisms of LV and RV dysfunction in HFpEF may provide a basis for an improved classification of HFpEF and for therapeutic approaches tailored to the molecular phenotype.

Background Implantable cardioverter defibrillators use low-voltage shock impedance measurements to monitor the lead integrity. However, previous case reports suggest that low-voltage shock impedance measurements may fail to detect insulation breaches that can cause life-threatening electrical short circuits. Methods and results We report six cases of insulation breaches in transvenous defibrillation leads that were not obvious during standard interrogations and testing of the lead beforehand. In two cases, an electrical short circuit during commanded shock delivery for internal electrical cardioversion resulted in a total damage of the ICD generator. In one of these cases, commanded shock delivery induced ventricular fibrillation, which required external defibrillation. In two cases, a shock due to ventricular tachycardia was aborted as the shock impedance was less than 20 Ω. However, in both cases the tiny residual shock energy terminated the ventricular tachycardia. In contrast, in one case the residual energy of the aborted shock did not end ventricular fibrillation induced at defibrillator threshold testing. In one case, the ICD indicated an error code for a short circuit condition detected during an adequate shock delivery. Conclusions This case series illustrates that low-voltage shock impedance measurements can fail to detect insulation breaches. These data suggest that in patients without a contraindication, traditional defibrillator threshold testing or high voltage synchronized shock at the time of device replacement should be considered.

The successful implementation and continuous development of sustainable corporate-level solutions is a challenge. These are endeavours in which social, environmental, and financial aspects must be weighed against each other. They can prove difficult to handle and, in some cases, almost unrealistic. Concepts such as green controlling, IT, and manufacturing look promising and are constantly evolving. This paper aims to achieve a better understanding of the field of corporate sustainability (CS). It will evaluate the hypothesis by which Corporate Sustainability thrives, via being efficient, increasing the performance, and raising the value of the input of the enterprises to the resources used. In fact, Corporate Sustainability on the surface could seem to contradict the idea, which supports the understanding that it encourages the reduction of the heavy reliance on the use of natural resources, the overall environmental impact, and above all, their protection. To understand how the contradictory notion of CS came about, in this part of the paper, the emphasis is placed on providing useful insight to this regard. The first part of this paper summarizes various definitions, organizational theories, and measures used for CS and its derivatives like green controlling, IT, and manufacturing. Second, a case study is given that combines the aforementioned sustainability models. In addition to evaluating the hypothesis, the overarching objective of this paper is to demonstrate the use of green controlling, IT, and manufacturing in the corporate sector. Furthermore, this paper outlines the current challenges and possible directions for CS in the future. Keywords: corporate sustainability, jevons paradox, efficiency side-effects, grey energy, rebound-effect.

Heart failure (HF) is responsible for substantial morbidity and mortality and is increasing in prevalence. Although there has been remarkable progress in the treatment of HF with reduced ejection fraction (HFrEF), morbidity and mortality are still substantial. Cardiac contractility modulation (CCM) signals, consisting of biphasic high-voltage bipolar signals delivered to the right ventricular septum during the absolute refractory period, have been shown to improve symptoms, exercise tolerance and quality of life and reduce the rate of HF hospitalizations in patients with ejection fractions (EF) between 25% and 45%. CCM therapy is currently approved in the European Union, China, India, Australia and Brazil for use in symptomatic HFrEF patients with normal or slightly prolonged QRS duration. CCM is particularly beneficial in patients with baseline EF between 35% and 45%, which includes half the range of HF patients with mid-range EFs (HFmrEF). At the cellular level, CCM has been shown in HFrEF patients to improve calcium handling, to reverse the foetal myocyte gene programme associated with HF, and to facilitate reverse remodelling. This review highlights the preclinical and clinical literature related to CCM in HFrEF and HFmrEF and outlines the potential of CCM for HF with preserved EF, concluding that CCM may fill an important unmet need in the therapeutic approach to HF across the range of EFs.

The purpose of this study was to analyze the potential usefulness and clinical relevance of adding left atrial (LA) strain to left atrial volume index (LAVI) in the detection of left ventricular diastolic dysfunction (LVDD) in patients with preserved left ventricular ejection fraction (LVEF).Recent studies have suggested that LA strain could be of use in the evaluation of LVDD. However, the potential utility and clinical significance of adding LA strain to LAVI in the detection of LVDD remains uncertain.Using 2-dimensional speckle-tracking echocardiography, we analyzed a population of 517 patients in sinus rhythm at risk for LVDD such as those with arterial hypertension, diabetes mellitus, or history of coronary artery disease and preserved LVEF.In patients with LV diastolic alterations and estimated elevated LV filling pressures, the rate of abnormal LA strain was significantly higher than an abnormal LAVI (62.4% vs. 33.6%, p 0.01). In line with this, in patients with normal LAVI, high rates of LV diastolic alterations and abnormal LA strain were present (rates 80% and 29.4%, respectively). In agreement with these findings, adding LA strain to LAVI in the current evaluation of LVDD increased significantly the rate of detection of LVDD (relative and absolute increase 73.3% and 9.9%; rate of detection of LVDD: from 13.5% to 23.4%; p 0.01). Regarding the clinical relevance of these findings, an abnormal LA strain (i.e., 23%) was significantly associated with worse New York Heart Association functional class, even when LAVI was normal. Moreover, in a retrospective post hoc analysis an abnormal LA strain had a significant association with the risk of heart failure hospitalization at 2 years (odds ratio: 6.6 [95% confidence interval: 2.6 to 16.6]) even adjusting this analysis for age and sex and in patients with normal LAVI.The findings from this study provide important insights regarding the potential usefulness and clinical relevance of adding LA strain to LAVI in the detection of LVDD in patients with preserved LVEF.

Background The high cardiovascular morbidity and mortality of patients with CKD may result in large part from medial vascular calcification, a process promoted by hyperphosphatemia and involving osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently been observed in patients with CKD, but the functional relevance of this remains unclear. Methods We performed experiments in primary human aortic VSMCs; klotho-hypomorphic (kl/kl), subtotal nephrectomy, and cholecalciferol-overload mouse calcification models; and serum samples from patients with CKD. Results In cultured VSMCs, treatment with zinc sulfate (ZnSO(4)) blunted phosphate-induced calcification, osteo-/chondrogenic signaling, and NF-κB activation. ZnSO(4) increased the abundance of zinc-finger protein TNF-α–induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-κB pathway, by zinc-sensing receptor ZnR/GPR39-dependent upregulation of TNFAIP3 gene expression. Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO(4) under high phosphate conditions. kl/kl mice showed reduced plasma zinc levels, and ZnSO(4) supplementation strongly blunted vascular calcification and aortic osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO(4) ameliorated vascular calcification in mice with chronic renal failure and mice with cholecalciferol overload. In patients with CKD, serum zinc concentrations inversely correlated with serum calcification propensity. Finally, ZnSO(4) ameliorated the osteoinductive effects of uremic serum in VSMCs. Conclusions Zinc supplementation ameliorates phosphate-induced osteo-/chondrogenic transdifferentiation of VSMCs and vascular calcification through an active cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and subsequent suppression of the NF-κB pathway. Zinc supplementation may be a simple treatment to reduce the burden of vascular calcification in CKD.

BACKGROUND AND AIMS Antiscatter grids improve image contrast by absorbing scattered x-ray beams, although by removing the antiscatter grid patient dose can be reduced as more x-ray beams reach the image receptor. Additionally, there is a trend toward ultra-low frame rates for radiation dose reduction during various electrophysiology procedures. As for most cardiac device implantations (CIED) image quality demands are usually modest, the purpose of this study was to assess the safety and efficacy of an ultra-low frame rate and scatter grid-less radiation protocol. METHODS/RESULTS A total of 140 patients undergoing CIED implantation between 2014 and 2017 were included in the study. Seventy patients (50%) implanted after implementation of the antiscatter grid-less and ultra-low frame rate protocol were matched to controls before the dose-reduction protocol was established. Forty patients (28.6%) had a one-chamber pacemaker or one-chamber implantable cardioverter defibrillator (ICD) implantation/revision, 60 (42.9%) had a two-chamber pacemaker or two-chamber ICD implantation/revision, and 40 (28.6%) patients had a cardiac resynchronization therapy device implantation/revision. Removing the antiscatter-grid and lowering the frame rate led to a 73% reduction of the overall dose area product (1,206 ± 2,015 vs 324 ± 422 μGym, P

Background A considerable amount of patients with typical atrial flutter develop atrial fibrillation after cavotricuspid isthmus (CTI) ablation. No uniform recommendations are available to guide anticoagulation regimes or electrocardiogram (ECG) monitoring strategies after this procedure. Methods We conducted a web-based survey in electrophysiology (EP) centers in Germany, Switzerland, and Austria. Responses were received from 47 centers. The survey was designed to investigate variations in management of the following: ablation strategy, oral anticoagulation (OAC) management, and ECG monitoring after successful CTI ablation. Results More than 55% of the participating centers assume that at least every third patient will develop atrial fibrillation during follow-up. Despite this assumption, most EP experts (81%) would still stop OAC after CTI ablation even in patients with higher CHADS2-VA2SC-score, or even perform CTI in asymptomatic patients with the purpose to stop OAC (52%). Most experts agree that ECG monitoring is necessary during follow-up. A majority still rely on short-term monitoring tools like resting ECGs (7%) or Holter ECGs (43%), while continuous monitoring by implantable loop recorders (10%) are rarely used for postablation OAC management. Conclusion A majority of the centers stop OAC in patients with higher CHADS2-VA2SC-score after CTI ablation. There is evidence that this practice might not be safe and lead to an increased number of ischemic strokes during follow-up. This reflects the need for prospective studies to allow for clear guidelines regarding these issues.

Ionizing radiation is an integral part of percutaneous coronary angiographies. Chronic exposure to low-dose radiation confers a risk for skin damage, eye lens opacities or cataracts, and malignant diseases to staff in the catheter laboratory. The RADPAD is a sterile surgical drape that reduces the effect of scatter radiation on the operator. We sought to assess the efficacy of RADPAD shields in reducing radiation dose experienced by operators during routine diagnostic coronary angiography. Sixty consecutive patients due to undergo elective coronary angiography were randomized in a 1:1 pattern to have their procedures performed with and without the RADPAD drape in situ. Dosimetry was performed on the left arm of the primary operator. There was no significant difference in the two main determents of radiation exposure in both groups: the screening times (102 ± 86 s for the RADPAD group vs. 105 ± 36 s for the control group, p = 0.9) and body mass index (BMI; 27.7 ± 4.2 kg/m2 for the RADPAD group vs. 27.9 ± 5.5 kg/m2 for the control group, p = 0.8). Moreover, there was no difference in the dose–area ratio (1337 ± 582 cGy/cm2 for the RADPAD group vs. 1541 ± 804 cGy/cm2 for the control group, p = 0.3) between the two patient groups. The primary operator radiation dose was significantly lower in the RADPAD group at 8.0 µSv (Q1: 3.2, Q3: 20.1) compared with 19.6 µSv (Q1: 7.1, Q3: 37.7) for the control group (p = 0.02). The RADPAD significantly reduces radiation exposure to primary operators during routine diagnostic coronary angiography in patients with a BMI > 25 kg/m2. It reduces total radiation exposure to primary operators by 59%, and the radiation exposure rate by 47%.

Key Clinical Message A patient developed a transient first-degree AV block during a radiofrequency ablation of an atrioventricular nodal reentrant tachycardia. Three days later the patient presented with a third-degree AV block. It resolved within 24 h under antiphlogistic therapy. Patient was asymptomatic without necessity for pacemaker implantation at 12 months follow-up.

Objectives Given the increasing prevalence of mobile phone and smartwatch use, this study tested patients with cardiovascular implantable electronic devices (CIEDs) for the incidence and consequence of contemporary mobile phone and smartwatch-produced electromagnetic interferences. Background Electromagnetic interferences can be hazardous for patients with CIEDs. Methods In total, 148 patients with CIEDs and leads from 4 different manufacturers were subjected to 1,352 tests. Analyzed CIEDs included 51 pacemakers, 5 cardiac resynchronization therapy pacemakers, 46 implantable cardioverter-defibrillators, 43 cardiac resynchronization therapy defibrillators, and 3 implantable loop recorders. To analyze a possible influence of certain distances between the mobile phone (iPhone 6) and the smartwatch (Apple Watch A1553) to the CIED, both were placed either directly above implanted devices or at the right wrist. All possible activations of the iPhone and the Apple Watch, including the standby, dialing, and connecting modes (telephone connection and Internet access) were tested. In addition, we studied incidence and characteristics of interferences with interrogation telemetry. Results In this study, only a single case of mobile phone–induced electromagnetic interference on a dual-chamber pacemaker was observed. Utilizing wanded telemetry, iPhone induced interferences were found in 14% of the patients. However, none of the patients showed any interference with the Apple Watch. Conclusions The risk of electromagnetic interferences of the iPhone 6 and the Apple Watch with CIEDs is low. However, close proximity of the iPhone 6 to implanted devices can cause telemetry interferences.

Introduction Radiofrequency (RF) ablation is a commonly used tool in the invasive electrophysiology laboratory to treat a variety of rhythm disorders. Reliable creation of transmural ablation lesions is crucial for long-term success. Lesion size index (LSI) is a multiparametric index that incorporates time, power, contact force (CF), and impedance data recorded during RF ablation in a weighted formula and has been shown to predict the extent of myocardial tissue lesions. Whether the force stability of contact influences lesion size in LSI-guided ablations is unknown. Objectives The aim of this study was to analyze the influence of the force stability of contact on lesion size during LSI-guided ablations in an ex-vivo model. Methods and results A total of 267 RF lesions (n = 6 hearts) were created on porcine myocardial slabs by using an open-tip irrigated ablation catheter with the following settings: 35 W with either intermittent (varied between 0 and up to 20 g), variable (10 to 20 g), or constant tissue contact (15 g) in a perpendicular or parallel fashion (applied manually) up to a target LSI of either 5 or 6. Subsequently, lesion width and depth were determined. Lesion width was mainly influenced by catheter tip orientation and LSI, whereas lesion depth was mainly influenced by LSI alone. The force stability of catheter contact had no relevant impact on lesion width or depth. Conclusion The force stability of catheter contact has only little effect on lesion depth or width in LSI-guided catheter ablation while the catheter orientation primarily affects lesion width.

BACKGROUND: A small proportion of patients undergoing primary prophylactic implantation of implantable cardioverter defibrillators (ICDs) experiences malignant arrhythmias. We postulated that periodic repolarisation dynamics, a novel marker of sympathetic-activity-associated repolarisation instability, could be used to identify electrically vulnerable patients who would benefit from prophylactic implantation of ICDs by way of a reduction in mortality. METHODS: We did a prespecified substudy of EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD), a prospective, investigator-initiated, non-randomised, controlled cohort study done at 44 centres in 15 EU countries. Patients aged 18 years or older with ischaemic or non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (≤35%) were eligible for inclusion if they met guideline-based criteria for primary prophylactic implantation of ICDs. Periodic repolarisation dynamics from 24-h Holter recordings were assessed blindly in patients the day before ICD implantation or on the day of study enrolment in patients who were conservatively managed. The primary endpoint was all-cause mortality. Propensity scoring and multivariable models were used to assess the interaction between periodic repolarisation dynamics and the treatment effect of ICDs on mortality. FINDINGS: Between May 12, 2014, and Sept 7, 2018, 1371 patients were enrolled in our study. 968 of these patients underwent ICD implantation, and 403 were treated conservatively. During follow-up (median 2·7 years [IQR 2·0-3·3] in the ICD group and 1·2 years [0·8-2·7] in the control group), 138 (14%) patients died in the ICD group and 64 (16%) patients died in the control group. We noted a 43% reduction in mortality in the ICD group compared with the control group (adjusted hazard ratio [HR] 0·57 [95% CI 0·41-0·79]; p=0·0008). Periodic repolarisation dynamics significantly predicted the treatment effect of ICDs on mortality (adjusted p=0·0307). The mortality benefits associated with ICD implantation were greater in patients with periodic repolarisation dynamics of 7·5 deg or higher (n=199; adjusted HR 0·25 [95% CI 0·13-0·47] for the ICD group vs the control group; p

Background: Implantable loop recorders (ILR) are a valuable tool for the investigation of unexplained syncopal episodes. The aim of this retrospective single center study was to identify predictive factors for pacemaker implantation in patients with unexplained syncope who underwent ILR insertion. Methods: One hundred six patients were retrospectively analyzed (mean age 59.1 years; 47.2% male) with unexplained syncope and negative conventional testing who underwent ILR implantation. The pri- mary study endpoint was detection of symptomatic or asymptomatic bradycardia requiring pacemaker implantation. Results: The average follow-up period after ILR implantation was 20 ± 15 months. Pacemaker im- plantation according to current guidelines was necessary in 22 (20.8%) patients, mean duration until index bradycardia was 81 ± 88 (2–350) days. Ten (45.5%) patients received a pacemaker due to sinus arrest, 7 (31.8%) patients due to third-degree atrioventricular block, 2 (9.1%) patients due to second- degree atrioventricular block and 1 (4.5%) patient due to atrial fibrillation with a slow ventricular rate. Three factors remained significant in multivariate analysis: obesity, which defined by a body mass index above 30 kg/m2 (OR: 7.39, p = 0.014), a right bundle branch block (OR: 9.40, p = 0.023) and chronic renal failure as defined by a glomerular filtration rate of less than 60 mL/min (OR: 6.42, p = 0.035). Conclusions: Bradycardia is a frequent finding in patients undergoing ILR implantation due to un- explained syncope. Obesity, right bundle branch block and chronic renal failure are independent clinical predictors of pacemaker implantation

Whereas adult cardiomyocytes are highly susceptible to stress, cardiomyocytes in the prenatal heart appear to be rather resistant. To investigate how embryonic cardiomyocytes respond to metabolic stress in vivo, we utilized tissue mosaicism for mitochondrial dysfunction in 13.5dpc mouse hearts. The latter is based on inactivation of the X-linked gene encoding Holocytochrome c synthase (Hccs), which is essential for mitochondrial respiration. In heterozygous heart conditional Hccs knockout females (cHccs(+/-)) random X chromosomal inactivation results in a mosaic of healthy and HCCS deficient cells in the myocardium. Microarray RNA expression analyses identified genes involved in unfolded protein response (UPR) and programmed cell death as differentially expressed in cHccs(+/-) versus control embryonic hearts. Activation of the UPR is localized to HCCS deficient cardiomyocytes but does not involve ER stress pathways, suggesting that it is caused by defective mitochondria. Consistently, mitochondrial chaperones, such as HSP10 and HSP60, but not ER chaperones are induced in defective cells. Mitochondrial dysfunction can result in oxidative stress, but no evidence for excessive ROS (reactive oxygen species) production was observed in cHccs(+/-) hearts. Instead, the antioxidative proteins SOD2 and PRDX3 are induced, suggesting that ROS detoxification prevents oxidative damage in HCCS deficient cardiomyocytes. Mitochondrial dysfunction and unrestricted UPR can induce cell death, and we detected the initiation of upstream events of both intrinsic as well as extrinsic apoptosis in cHccs(+/-) hearts. Cell death is not executed, however, suggesting the activation of antiapoptotic mechanisms. Whereas most apoptosis inhibitors are either unchanged or downregulated in HCCS deficient cardiomyocytes, Bcl-2 and ARC (apoptosis repressor with caspase recruitment domain) are induced. Given that ARC can inhibit both apoptotic pathways as well as necrosis and attenuates UPR, we generated cHccs(+/-) embryos on an Arc knockout background (cHccs(+/-),Arc(-/-)). Surprisingly, the absence of ARC does not induce cell death in embryonic or postnatal HCCS deficient cardiomyocytes and adult cHccs(+/-),Arc(-/-) mice exhibit normal cardiac morphology and function. Taken together, our data demonstrate an impressive plasticity of embryonic cardiomyocytes to respond to metabolic stress, the loss of which might be involved in the high susceptibility of postnatal cardiomyocytes to cell death.

Objective— Drug-eluting coronary stents reduce restenosis rate and late lumen loss compared with bare-metal stents; however, drug-eluting coronary stents may delay vascular healing and increase late stent thrombosis. The peroxisome proliferator–activated receptor-delta (PPARδ) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement. Approach and Results— Here, we report that PPARδ ligand–coated stents strongly reduce the development of neointima and luminal narrowing in a rabbit model of experimental atherosclerosis. Inhibition of inflammatory gene expression and vascular smooth muscle cell (VSMC) proliferation and migration, prevention of thrombocyte activation and aggregation, and proproliferative effects on endothelial cells were identified as key mechanisms for the prevention of restenosis. Using normal and PPARδ-depleted VSMCs, we show that the observed effects of PPARδ ligand GW0742 on VSMCs and thrombocytes are PPARδ receptor dependent. PPARδ ligand treatment induces expression of pyruvate dehydrogenase kinase isozyme 4 and downregulates the glucose transporter 1 in VSMCs, thus impairing the ability of VSMCs to provide the increased energy demands required for growth factor–stimulated proliferation and migration. Conclusions— In contrast to commonly used drugs for stent coating, PPARδ ligands not only inhibit inflammatory response and proliferation of VSMCs but also prevent thrombocyte activation and support vessel re-endothelialization. Thus, pharmacological PPARδ activation could be a promising novel strategy to improve drug-eluting coronary stents outcomes.

Die hypertrophe Kardiomyopathie (HCM) ist eine vererbbare Erkrankung, die zu einer Verdickung der linksventrikularen Wand mit oder ohne gleichzeitige Obstruktion des linksventrikularen Ausflusstraktes fuhrt. Neben der symptomatischen Therapie ist eine Risikostratifizierung der Patienten mit HCM essentiell, da es bei den Erkrankten zu lebensbedrohlichen ventrikularen Herzrhythmusstorungen kommen kann. 2013 wurde in der HCM-Risk-SCD-Studie anhand von 3675 Patienten mit HCM und uber 24 313 Patientenjahren im follow-up ein neues Pradiktionsmodell fur den plotzlichen Herztod entwickelt. Dieses Modell wurde so auch in die Leitlinien der Europaischen Gesellschaft fur Kardiologie mit aufgenommen. In dieser Ubersichtarbeit sollen das Pradiktionsmodell und die daraus resultierenden Empfehlungen einschlieslich der damit verbundenen Limitationen und Risiken diskutiert werden.

Background The purpose of this meta-analysis was to analyze the clinical relevance of left atrial (LA) strain to predict recurrence of atrial fibrillation (AF) after catheter ablation (CA). Methods and Results We searched in different databases (Medline, EMBASE, and Cochrane) prospective studies that analyzed LA strain before CA. Eight studies (2 with only paroxysmal AF and 6 with mixed population of paroxysmal and persistent AF) were included in the final analysis (total patient number = 686). Patients with recurrence of AF were principally characterized by lower LA strain in comparison with those without AF recurrence (mean 18.4% [range 8.8–24.5%] versus 25.3% [13.6–32.7%], weighted mean difference −4.89% [95% CI −5.83% to −3.95%], P < 0.001). In addition, receiver operating curves shown that LA strain was strongly associated with recurrence of AF after CA (weighted mean: AUC 0.798 [95% CI 0.700–0.943], cutoff 22.8% [18.8–30%], sensitivity 78% [65–86%], and specificity 75% [66–100%]). In line, these results were similar using LA strain with QRS-analysis and P-analysis as well as using different software package such as Echo-Pac, QLab, TomTec, and VVI. Conclusion In patients with AF candidate for CA, the analysis of the LA using LA strain could be of great usefulness to identify patients with high risk of AF recurrence. Nonetheless, further studies are needed to establish the clinical relevance of LA strain in patients with persistent AF.