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Abstract Glucosinolates, vitamin C, carotenoids and vitamin K1 concentrations were determined in different parts of the Brussels sprouts buds (outer leaves, middle leaves and core) and the Brussels sprouts plant (stem, buds, petioles and leaves). The outer leaves of the Brussels sprouts buds contained ≈26%, ≈95% and ≈59% more vitamin C, carotenoids and vitamin K1, respectively, compared to the core. Total glucosinolates concentrations were evenly distributed, although their profile was different. Regarding the Brussels sprouts plant, glucosinolates were mainly present in the stem (153 ± 21 mg/ 100 g fresh weight) and the buds (88 ± 8 mg/100 g fresh weight). Carotenoids and vitamin K1 were distinctly more present in the leaves (24 ± 1 mg/ 100 g fresh weight and 0.62 ± 0.07 mg/ 100 g fresh weight, respectively). The buds contained 44 to 50% more vitamin C (85 ± 3 mg/ 100 g fresh weight) than the other parts of the Brussels sprouts plant. Graphical Abstract

Type 1 diabetes (T1D) is characterized by a prolonged autoimmune attack resulting in the massive loss of insulin-producing beta cells. The initiation and progression of T1D depends on a complex interaction between genetic, immunological and environmental factors. Epidemiological, experimental and clinical evidence suggest a link between viral infections, particularly Coxsackievirus type B (CVB), and T1D development. Specifically, infections by the CVB serotype 1 (CVB1) contribute to the triggering of autoimmunity against beta cells in genetically predisposed individuals, and prolonged and probably non-lytic infections by CVB are associated with the development of T1D. However, the molecular mechanisms underlying CVB1 replication and establishing persistent infections in human pancreatic beta cells remain poorly understood. Here we show that the N6-methyladenosine (m6A) RNA epigenetic modification machinery regulates CVB1 amplification in the human beta cells. Using small interfering RNA (siRNA) targeting m6A writers and erasers, we observed that downregulation of m6A writers increases CVB1 amplification, while the downregulation of m6A erasers decreases it. Notably, the inhibition of Fat Mass and Obesity-associated protein (FTO), a key m6A eraser, reduced by 95% the production of infectious CVB1 in both human insulin-producing EndoC-βH1 cells and in induced pluripotent stem cell (iPSC)-derived islets. The FTO inhibitor reduced CVB1 expression within 6 h post-infection, suggesting a direct regulation of the CVB1 genome by m6A modification. Furthermore, in the absence of viral replication, FTO inhibition also decreased the translation of the incoming CVB1 genome, indicating that m6A plays a critical role in the initial stages of viral RNA translation. In addition, modulation of the m6A machinery affected the type I interferon response after poly-IC transfection, a mimic of RNA virus replication, but did not affect the cellular antiviral response in CVB1-infected cells. Altogether, these observations suggest that m6A directly affects CVB1 production. Our study provides the first evidence that the m6A epigenetic modification machinery controls CVB amplification in human pancreatic beta cells. This suggests that the m6A machinery is a potential target to control CVB infection in T1D and raises the possibility of an epigenetic control in the establishment of persistent CVB infections observed in the pancreas in individuals with type 1 diabetes.

This study investigated the impact of preparation processes (as applied in large-scale kitchens) on the resulting sensory and health-related quality aspects starting from industrially blanched and frozen Brussels sprouts. A single (steaming) and a double-heat (steaming and reheating) preparation were considered. Consumers consume vegetables both whole and as disintegrated (puree-like) systems. Hence, in this study, two distinct pretreatment conditions (i.e., intact Brussels sprouts and Brussels sprouts puree) included in the preparation processes. It was observed that steaming intact Brussels sprouts via both preparation methods did affect the quality, but only to a limited extent, possibly explained by the fact that the starting material was blanched. Pretreatment was observed to be a determinative step, as also observed in the fact that the quality of puree-systems was more affected upon processing compared to the quality of the intact Brussels sprouts. GSLs and volatile profiles were indeed not observed to be affected largely upon preparation and reheating processing. However, vitamin C concentration did lead to loss of 38–45% due to heat and exposure to oxygen. In conclusion, pretreatment (e.g., blanching and disintegrating) is considered the most determinative step in affecting the resulting quality of Brussels sprouts, which can be kept in mind for industrial and home practices.

This article is a French translation of the paper “Multi-criteria study on a change to a fruit-free diet in Cebidae and Cercopithecidae” published on October 31, 2023 in the Journal of Zoo and Aquarium Research (citation: Viallard, F., Lefebvre, S., Petry, A., Vonfeld, I., & Quintard, B. (2023). Multicriteria study on the transition to a fruitless diet in Cebidae and Cercopithecidae. Journal of Zoo and Aquarium Research, 11(4), 376-383. https://doi.org/10.19227/jzar.v11i4.738). Nutrient intake of captive primates does not necessarily reflect that of their wild counterparts. Diets in captivity are often higher in non-structural carbohydrates and lower in fibre, resulting in health issues such as obesity, dental issues, diarrhoea and behavioural problems. The main objective of this study was to establish and monitor a change to a fruit-free diet in five species of primates (Ateles fusciceps rufiventris, Cercopithecus hamlyni, Allochrocebus lhoesti, Cercopithecus roloway, Sapajus xanthosternos). Nutrition and ethology was monitored, including an assessment of the nutritional composition of diets before, during and after diet change; monitoring of faeces consistency; observation of feeding choices; and the occurrence of aggressive behaviour and vocalisations by scan sampling. The initial diet included cultivated fruits and vegetables and some extras (cereals, animal and vegetable proteins) and was higher in non-structural carbohydrates, in particular sugar, than recommended in husbandry guidelines. After a diet change of four weeks during which fruits were gradually removed, a decrease of mean sugar content by more than half and an increase in fibre was achieved. Improved faeces consistency was observed for spider monkeys A. f. rufiventris and Hamlyn monkeys C. hamlyni (change in Bristol stool score: 6 to 4 and 7 to 3, respectively). An increase in time spent feeding was observed for capuchins S. xanthosternos and Hamlyn monkeys (1.5 to 2 times longer). These findings underline the beneficial effects of changing to fruit-free high-fibre diets in zoo-managed primates.

Abstract Urban mobility contributes significantly to greenhouse gas emissions and comes with negative social impacts for various groups, such as limited accessibility to opportunity or basic services. Transitions towards sustainable and people-centred urban mobility systems are paramount. Yet, this is accompanied by various challenges. Complex urban systems are accompanied by high uncertainties (e.g., technological progress, demographics, climate change) which are currently not well integrated. Possible solutions originate from design, policymaking, and innovation, with a widespread disconnection due to non-compatible methods. This paper presents a method to improve the ability to design future urban mobility systems by integrating different approaches for modelling what the future could be and who could be the users. The research question is how diverse future user needs can be integrated in design processes for urban mobility systems. The proposed scenario-based design and personas allows to create data-driven proto-personas—a set of archetypical users with assigned characteristics and behaviours—test their validity, derive distributions across geographical areas, and transform them for different 2030 scenarios. This serves as input to create full personas and synthetic populations as intermediary design objects for the collaboration of designers and simulation experts. The methodology is exemplarily applied in the context of Paris. It contributes to urban mobility solution design that is more aware of future uncertainty and diverse needs of users, therefore, better capable to respond to today’s challenges. The approach is replicable with open data and accessible source code: https://github.com/TjarkGall/proto-persona-clustering .

How complex organics form in a prebiotic world remains a missing key to establish where life emerged. The authors present a road to abiotic organic synthesis and diversification in hydrothermal contexts involving magmatism and rock hydration.

We report a case of a clinically asymptomatic patient with extreme P-wave separation on the electrocardiogram mimicking atrial tachycardia with atrioventricular block. The accurate examination of the patient, analysis of the electrocardiogram, and echocardiographic findings led to proper diagnosis, management, and treatment. (Level of Difficulty: Intermediate.)

(Series Information) European Papers - A Journal on Law and Integration, 2022 7(1), 481-506 | Article | (Table of Contents) I. Introduction. - II. The case of the ESM: why the Eurozone's governance does not question the unity of the EU institutional framework. - II.1. The establishment of the ESM. - II.2. The institutional functioning of the ESM. - III. The impact of tasks entrusted to the EU institutions under the ESM on the institutional equilibrium within the EU legal order. - III.1. How are new tasks entrusted to the EU institutions? - III.2. What impact do these new tasks produce on the institutional equilibrium within the EU? - IV. The post-Covid institutional set-up: back to a "community" mode of governance? - V. Conclusion. | (Abstract) In the aftermath of the global financial crisis, the EU and its Member States had to face very pragmatic issues: how to avoid the economic collapse of Greece, Portugal and Ireland? Decisions had to be taken quickly in any institutional or legal forum that was immediately available. For this specific reason, legal solutions entailing the conclusion of international agreements by some of the EU Member States outside the EU legal framework were taken as a new normal. Due to a close legal relationship between these new international treaties and the EU legal order, a decision was also taken to "borrow" already existing EU institutions and entrust them with new tasks. In this Article, we question the role of EU institutions outside the EU legal framework. We first address the evolution of the EU institutional framework in the context of the euro crisis in relation to art. 13 TEU and recital 7 of the TEU preamble and the requirement of "unity of the institutional framework". Section II shows that "borrowing" the EU institutions outside the EU legal framework does not seem to alter the nature of the single EU institutional setting. Section III questions whether the tasks entrusted to the EU institutions outside the EU legal framework do not undermine the existing institutional equilibrium within the EU legal order. Section IV addresses the EU response to the Covid-19 pandemic from an institutional perspective as raising similar concerns within the EU legal order. The last section concludes.

The Ardèche department is often vaunted today for its attractive natural landscapes and its historic heritage, but it stands out in French industrial history for its production of thrown silk, accounting for half of national production during the nineteenth century. The thrown silk is obtained during a little-known intermediate stage in the industry, called ‘moulinage’ in French, silk-throwing, situated between ‘filature’, the spinning, or, more precisely, the reeling of raw silk from the cocoons, and weaving. The process gives twists to one or several threads of hard silk, making them hold together but also giving the silk a series of other qualities such as brilliance, resistance, elasticity, and so on. The work we undertook for our geography thesis on the territory of the natural regional park of the Ardèche Mountains tried to answer a simple question: what has become of this industrial heritage? Between disappearance and conceptualisation as heritage, between inventory notices and citizens initiatives, our article looks at different forms of interpretation and promotion. To begin with we examine the industrial heritage itself, both physical and intangible, observing this heritage in the light of its links with the surrounding rural environment. We then go on to an analysis of the situation and the uses to which the heritage is put today, in keeping with different territorial tendencies within the department. And we conclude by asking what particularities can be observed in the heritagisation processes at work.

Le travail proposé ici est une première exploration de la reconversion du patrimoine industriel sur le territoire du Parc naturel régional des Monts d’Ardèche, étudié dans le cadre d’une thèse CIFRE en géographie. Après être revenus sur les paradoxes imposant le statut de marge à ces formes de patrimonialisation, nous proposons un tour d’horizon des reconversions ardéchoises construit à partir d’un recensement des sites industriels. L’objectif est de cibler ce que ces projets questionnent en termes de ressources patrimoniales, d’habiter et de communs. L’émergence de certaines initiatives, nos cas d’études, de reconversion inventive nous amènerons enfin à discuter des recompositions induites sur les ruralités et plus globalement sur les transformations sociétales actuelles.

The current global systemic crisis reveals how globalised societies are unprepared to face a pandemic. Beyond the dramatic loss of human life, the COVID-19 pandemic has triggered widespread disturbances in health, social, economic, environmental and governance systems in many countries across the world. Resilience describes the capacities of natural and human systems to prevent, react to and recover from shocks. Societal resilience to the current COVID-19 pandemic relates to the ability of societies in maintaining their core functions while minimising the impact of the pandemic and other societal effects. Drawing on the emerging evidence about resilience in health, social, economic, environmental and governance systems, this paper delineates a multisystemic understanding of societal resilience to COVID-19. Such an understanding provides the foundation for an integrated approach to build societal resilience to current and future pandemics.

Pulsed electric fields (PEF) at low field strength is considered a non-thermal technique allowing membrane permeabilization in plant-based tissue, hence possibly impacting biochemical conversions and the concomitant volatile profile. Detailed studies on the impact of PEF at low field strength on biochemical conversions in plant-based matrices are scarce but urgently needed to provide the necessary scientific basis allowing to open a potential promising field of applications. As a first objective, the effect of PEF and other treatments that aim to steer biochemical conversions on the volatile profile of Brussels sprouts was compared in this study. As a second objective, the effect of varying PEF conditions on the volatile profile of Brussels sprouts was elucidated. Volatile fingerprinting was used to deduce whether and which (bio)chemical reactions had occurred. Surprisingly, PEF at 1.01 kV/cm and 2.7 kJ/kg prior to heating was assumed not to have caused significant membrane permeabilization since similar volatiles were observed in the case of only heating, as opposed to mixing. A PEF treatment with an electrical field strength of 3.00 kV/cm led to a significantly higher formation of certain enzymatic reaction products, being more pronounced when combined with an energy input of 27.7 kJ/kg, implying that these PEF conditions could induce substantial membrane permeabilization. The results of this study can be utilized to steer enzymatic conversions towards an intended volatile profile of Brussels sprouts by applying PEF.

Aims: The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca(2+), Na(+), K(+)) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes.Methods and Results: Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis.Conclusion: The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. Clinicaltrials.gov identifier: NCT01209494. [ABSTRACT FROM AUTHOR]

Objectives. The aim of the study was to compare elastographic means in parathyroid adenomas, using shear wave elastography and strain elastography. Methods. This prospective study examined 20 consecutive patients diagnosed with primary hyperparathyroidism and parathyroid adenoma, confirmed by biochemical assay, technetium-99 sestamibi scintigraphy, and pathology report, after parathyroid surgery. All patients were examined on conventional 2B ultrasound, 2D shear wave elastography, and strain elastography. We determined using 2D shear wave elastography (SWE) the elasticity index (EI) in parathyroid adenoma, thyroid parenchyma, and surrounding muscle and examined using strain elastography the parathyroid adenoma, and determined the strain ratio with the thyroid tissue and muscle tissue. Results. All patients had positive sestamibi scintigraphy and underwent surgery, with confirmation of parathyroid adenoma in all cases. The mean parathormone (PTH) value before surgery was 153.29 pg/ml (36.5, 464.8) and serum calcium concentration was 10.5 mg/dl (9, 11.5). We compared using 2D-SWE and strain elastography parathyroid adenoma with thyroid tissue and with surrounding muscle. The mean EI measured by SWE in parathyroid adenoma was 4.74 ± 2.74 kPa and in thyroid parenchyma was 11.718 ± 4.206 kPa (mean difference = 6.978 kPa, p

Travelers interact with a large number and variety of products and services during their journeys. The quality of a travel experience depends on a whole urban mobility system considered in space and time. This paper outlines the relevant concepts to be considered in designing urban mobility. The goal is to provide a language and insights for the early stages of a design process. A literature review sheds light on the complexity of urban mobility from technical, sociotechnical, and user experience perspectives. Observations of experiences in urban areas provide data for describing and understanding travel experience patterns and issues. The paper proposes a conceptual model to describe and analyze different facets of traveler experience and categorizes problems that travelers face when they interact with an urban mobility system. A case study is reported illustrating the use of the conceptual model in identifying travel problems for a demand-responsive transport service.

Fine needle aspiration (FNA) is considered the gold standard in the diagnostic of thyroid nodules. Using the recommended BETHESDA reporting system, up to 20% of results are classified as intermediate cytology. As there is no consensus whether ultrasound evaluation, lobectomy or surgery is the best treatment option, intermediate cytology results are considered a grey zone of the FNA. The main aim of our study was to evaluate the performance of combined advanced ultrasound techniques in the process of diagnosis and evaluation of the intermediate cytology cases after FNA. We evaluated 54 consecutive cases with intermediate cytology on FNA, using conventional B-mode ultrasound (2B), and strain elastography, using a linear multifrequency 6−13 MHz linear probe (Hitachi Prerius Machine, Hitachi Inc, Japan). All nodules were classified with our Thyroid Imaging Report and Data System (TI-RADS) proposed model, considering: vertical appearance, with antero-posterior diameter bigger than the transvers diameter, the so called taller than wide shape, irregular borders, intranodular inhomogeneity, marked hypoecogenicity, micro calcifications, the presence of suspect lymph nodes, and increased stiffness as suspicious for malignancy. The classification outcomes were compared with the pathology results, considered the gold standard diagnosis. The prevalence of cancer was 28.8%, with 13/45 cases having a clear diagnostic of cancer. Six cases were diagnosed with borderline follicular neoplasia, a category with unclear evolution, also considered as malignant in the analysis of the imaging results. In total, 16/19 cancer cases had increased stiffness on elastography. The cancer prevalence increased with TI-RADS category, being 25% in TI-RADS 4b category and 92.8% in TI-RADS 5 category. The AUROC (Area Under Receiver Operating Curve) of elastography alone, in differentiation of malignant thyroid nodules was 74.9%; the combination of elastographic and conventional ultrasound characteristics generated an even better AUROC, of 84.5%. The combined conventional ultrasound and elastography identified thyroid cancer in cases with intermediate cytology with a sensitivity of 89.5% with a specificity of 50%. High risk thyroid nodules, identified by combined high risk conventional ultrasound characteristics and increased stiffness, on strain elastography, are highly predictive for malignancy, in the intermediate cytology cases.

Intrauterine growth restriction (IUGR) in preterm infants increases the risk of bronchopulmonary dysplasia, characterized by arrested alveolarization. We evaluated the impact of two different rat models (nitric oxide synthase inhibition or protein deprivation) of IUGR on alveolarization, before, during, and at the end of this postnatal process. We studied IUGR rat pups of dams fed either a low protein (LPD) or a normal diet throughout gestation and pups of dams treated by continuous infusion of Nω-nitro-L-arginine methyl ester (L-NAME) or its diluent on the last four days of gestation. Morphometric parameters, alveolar surface (Svap), mean linear intercept (MLI) and radial alveolar count (RAC) and transcriptomic analysis were determined with special focus on genes involved in alveolarization. IUGR pups regained normal weight at day 21 in the two treated groups. In the LPD group, Svap, MLI and RAC were not different from those of controls at day 4, but were significantly decreased at day 21, indicating alveolarization arrest. In the L-NAME group, Svap and RAC were significantly decreased and MLI was increased at day 4 with complete correction at day 21. In the L-NAME model, several factors involved in alveolarization, VEGF, VEGF-R1 and -R2, MMP14, MMP16, FGFR3 and 4, FGF18 and 7, were significantly decreased at day 4 and/or day 10, while the various factors studied were not modified in the LPD group. These results demonstrate that only maternal protein deprivation leads to sustained impairment of alveolarization in rat pups, whereas L-NAME impairs lung development before alveolarization. Known growth factors involved in lung development do not seem to be involved in LPD-induced alveolarization disorders, raising the question of a possible programming of altered alveolarization.

Background: Despite transcatheter aortic valve implantation (TAVI) having become a routine procedure, access site bleeding and vascular complications are still a concern which contribute to procedure-related morbidity and mortality., Aims: The TAVI-MultiCLOSE study aimed to assess the safety and efficacy of a new vascular closure algorithm for percutaneous large-bore arterial access closure following transfemoral (TF)-TAVI., Methods: All consecutive TF-TAVI cases in which the MultiCLOSE vascular closure algorithm was used were prospectively included in a multicentre, observational study. This stepwise algorithm entails the reinsertion of a 6-8 Fr sheath (primary access) following the initial preclosure with one or two suture-based vascular closure devices (VCDs). This provides the operator with the opportunity to perform a quick and easy angiographic control and tailor the final vascular closure with either an additional suture- or plug-based VCD, or neither of these., Results: Among 630 patients who underwent TF-TAVI utilising the MultiCLOSE algorithm, complete arterial haemostasis was achieved in 616 patients (98%). VCD failure occurred in 14 patients (2%), treated with either balloon inflation (N=1), covered stent (N=12) or surgical repair (N=1). Overall, this vascular closure approach resulted in a minor and major vascular complication rate of 2.2% and 0.6%, respectively. At 30 days, only one new minor vascular complication (0.2%) was noted. In-hospital and 30-day all-cause mortality rates were 0.2% and 1.0%, respectively., Conclusions: Use of the MultiCLOSE vascular closure algorithm was demonstrated to contribute to an easy, safe, efficacious and durable vascular closure after TF-TAVI, resulting in a major vascular complication rate of less than 1%.

Objectives: This study aimed to assess discordance between results of instantaneous wave-free ratio (iFR), fractional flow reserve (FFR), and intravascular ultrasound (IVUS) in intermediate left main coronary (LM) lesions, and its impact on clinical decision making and outcome., Methods: We enrolled 250 patients with a 40%-80% LM stenosis in a prospective, multicenter registry. These patients underwent both iFR and FFR measurements. Of these, 86 underwent IVUS and assessment of the minimal lumen area (MLA), with a 6 mm2 cutoff for significance., Results: Isolated LM disease was recognized in 95 patients (38.0%), while 155 patients (62.0%) had both LM disease and downstream disease. In 53.2% of iFR+ and 56.7% of FFR+ LM lesions, the measurement was positive in only one daughter vessel. iFR/FFR discordance occurred in 25.0% of patients with isolated LM disease and 36.2% of patients with concomitant downstream disease (P=.049). In patients with isolated LM disease, discordance was significantly more common in the left anterior descending artery and younger age was an independent predictor of iFR-/FFR+ discordance. iFR/MLA and FFR/MLA discordance occurred in 37.0% and 29.4%, respectively. Within 1 year of follow-up, major cardiac adverse events (MACE) occurred in 8.5% and 9.7% (P=.763) of patients whose LM lesion was deferred or revascularized, respectively. Discordance was not an independent predictor of MACE., Conclusions: Current methods of estimating LM lesion significance often yield discrepant findings, complicating therapeutic decision-making.

Background: Stroke is a major concern in transcatheter aortic valve replacement (TAVR). The introduction of a cerebral protection devices may counteract the evolution towards minimally invasive TAVR. At this time, there is insufficient data to support the routine use of these devices., Methods: We aimed to evaluate the outcome of the routine use of the Sentinel Cerebral protection system ® (CPS) in patients undergoing TAVR, after completing a CT-based screening process for feasibility of Sentinel implantation. We report our initial experience with the routine implementation of the Sentinel CPS in all anatomically suitable patients undergoing TAVR. We retrospectively compared the procedural characteristics and outcomes between all TAVR patients treated with ( n  = 78) and without ( n  = 79) intended Sentinel., Results: The Sentinel CPS could successfully be deployed in 99% of intended cases after CT feasibility screening. TAVR procedures with Sentinel CPS were not longer than procedures without Sentinel use (89 ± 20 versus 120 ± 50 min, p  = 0.007). Sentinel CPS use was not associated with an increased risk of procedural complications. Stroke was observed in none (0%) of the Sentinel CPS patients, and in 6.3% of the non-Sentinel CPS patients ( p  = 0.05). The finding of stroke was associated with a high risk of early postprocedural mortality: 60% of stroke patients died within 3 months., Conclusion: Routine use of the Sentinel CPS in CT-screened TAVR patients is feasible with high procedural success, without significant adverse events and without counteracting the evolution towards minimally invasive TAVR. Clinically relevant stroke was observed in none of the Sentinel CPS patients.

Combining myocardial perfusion single photon emission computed tomography (SPECT-MPI) and coronary computed tomography angiography (CCTA) is an interesting hybrid imaging option in modern cardiovascular medicine. The integrated hybrid technique has a number of advantages compared to visual side-by-side analysis of the separate modalities. CT attenuation map can correct for attenuation artefacts and thus improve the diagnostic accuracy of SPECT-MPI. Moreover, the anatomical information of the CCTA and the perfusion map of SPECT-MPI allow for vessel-based correlation and culprit vessel identification. Combining SPECT-MPI with CCTA is an appealing tool in the work-up of complex ischaemic heart disease and might help determine the optimal treatment strategy. This case series illustrates the role of SPECT-CCTA in decision-making of revascularization strategy in complex ischaemic heart disease.

Background: Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) improve sensitivity of cardiac allograft vasculopathy (CAV) detection compared to invasive coronary angiography (ICA), but their ability to predict clinical events is unknown. We determined whether severe CAV detected with ICA, IVUS, or OCT correlates with graft function., Methods: Comparison of specific vessel parameters between IVUS and OCT on 20 patients attending for angiography 12-24 months post-orthotopic heart transplant. Serial left ventricular ejection fraction (EF) was recorded prospectively., Results: Analyzing 55 coronary arteries, OCT and IVUS correlated well for vessel CAV characteristics. A mean intimal thickness (MIT) OCT  > .25 mm had a sensitivity of 86.7% and specificity of 74.3% at detecting Stanford grade 4 CAV. Those with angiographically evident CAV had significant reduction in graft EF over 7.3 years follow-up (median ΔEF -2% vs +1.5%, P = .03). Patients with MIT OCT  > .25 mm in at least one vessel had a lower median EF at time of surveillance (57% vs 62%, P = .014). Two MACEs were noted., Conclusion: Imaging with OCT correlates well with IVUS for CAV detection. Combined angiography and OCT to screen for CAV within 12-24 months of transplant predicts concurrent and future deterioration in graft function., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: The current study assessed the impact of COVID-19-related public containment measures (i.e. lockdown) on the ST elevation myocardial infarction (STEMI) epidemic in Belgium., Methods and Results: Clinical characteristics, reperfusion therapy modalities, COVID-19 status and in-hospital mortality of consecutive STEMI patients who were admitted to Belgian hospitals for percutaneous coronary intervention (PCI) were recorded during a three-week period starting at the beginning of the lockdown period on 13 March 2020. Similar data were collected for the same time period for 2017-2019. An evaluation of air quality revealed a 32% decrease in ambient NO 2 concentrations during lockdown (19.5 µg/m³ versus 13.2 µg/m³, p  < .001). During the three-week period, there were 188 STEMI patients admitted for PCI during the lockdown versus an average 254 STEMI patients before the lockdown period (incidence rate ratio = 0.74, p  = .001). Reperfusion strategy was predominantly primary PCI in both time periods (96% versus 95%). However, there was a significant delay in treatment during the lockdown period, with more late presentations (>12 h after onset of pain) (14% versus 7.6%, p  = .04) and with longer door-to-balloon times (median of 45 versus 39 min, p  = .02). Although the in-hospital mortality between the two periods was comparable (5.9% versus 6.7%), 5 of the 7 (71%) COVID-19-positive STEMI patients died., Conclusion: The present study revealed a 26% reduction in STEMI admissions and a delay in treatment of STEMI patients. Less exposure to external STEMI triggers (such as ambient air pollution) and/or reluctance to seek medical care are possible explanations of this observation.

Background: Noninvasive risk stratification aims to detect abnormalities in the pathophysiological mechanisms underlying ventricular arrhythmias. We studied the predictive value of repeating risk stratification in patients with an implantable cardioverter-defibrillator (ICD)., Methods: The EUTrigTreat clinical study was a prospective multicenter trial including ischemic and nonischemic cardiomyopathies and arrhythmogenic heart disease. Left ventricular ejection fraction ≤40% (LVEF), premature ventricular complexes >400/24 hr (PVC), non-negative microvolt T-wave alternans (MTWA), and abnormal heart rate turbulence (HRT) were considered high risk. Tests were repeated within 12 months after inclusion. Adjusted Cox regression analysis was performed for mortality and appropriate ICD shocks., Results: In total, 635 patients had analyzable baseline data with a median follow-up of 4.4 years. Worsening of LVEF was associated with increased mortality (HR 3.59, 95% CI 1.17-11.04), as was consistent abnormal HRT (HR 8.34, 95%CI 1.06-65.54). HRT improvement was associated with improved survival when compared to consistent abnormal HRT (HR 0.10, 95%CI 0.01-0.82). For appropriate ICD shocks, a non-negative MTWA test or high PVC count at any moment was associated with increased arrhythmic risk independent of the evolution of test results (worsening: HR 3.76 (95%CI 1.43-9.88) and HR 2.50 (95%CI 1.15-5.46); improvement: HR 2.80 (95%CI 1.03-7.61) and HR 2.45 (95%CI 1.07-5.62); consistent: HR 2.47 (95%CI 0.95-6.45) and HR 2.40 (95%CI 1.33-4.33), respectively). LVEF improvement was associated with a lower arrhythmic risk (HR 0.34, 95%CI 0.12-0.94)., Conclusions: Repeating LVEF and HRT improved the prediction of mortality, whereas stratification of ventricular arrhythmias may be improved by repeating LVEF measurements, MTWA and ECG Holter monitoring., (© 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Aims: We aimed to investigate the effects of an initial learning period with mandatory optical coherence tomography (OCT) guidance for the implantation of everolimus-eluting bioresorbable vascular scaffolds (BVS)., Methods and Results: We analysed procedural and clinical outcomes of all BVS implantations at a single centre where OCT guidance was mandatory in the initial rollout (OCT-mandatory) phase. We compared these data with the later phase where use of OCT was at operator discretion (OCT-selective or angiography). We implanted 406 BVS in 306 vessels (201 OCT, 105 angiography) in 272 patients. Follow-up duration was 38±10 months. Annualised rates of device-oriented cardiac events (DOCE) and scaffold thrombosis (ScT) were 1.4% and 0.4%, respectively. The risks of DOCE (HR 1.06, 95% CI: 0.33-3.34; p=0.71) and ScT (HR 0.48, 95% CI: 0.07-3.85; p=0.49) were not significantly different when comparing the OCT and angiography groups., Conclusions: Routine use of OCT to guide and optimise BVS implants results in very acceptable outcomes. Further, the benefits of such an early OCT-mandatory "learning" period persist after cessation of routine OCT usage when imaging is not routinely used. A period of mandatory OCT usage for BVS implants may therefore be beneficial in improving patient outcomes with these devices.

Background: Percutaneous coronary interventions (PCI) of old calcified saphenous vein grafts (SVGs) is challenging and is associated with a considerably high risk of adverse ischemic events in the short- and long-term as compared to native coronary arteries. We report a case in which a non-dilatable, calcified SVG lesion is successfully treated with rotational atherectomy followed by PCI and stenting with local stent delivery (LSD) technique using the Guidezilla™ guide extension catheter (5-in-6 Fr) in the "child-in-mother" fashion., Case Presentation: A 70 years-old man with a dilated ischemic cardiomyopathy, triple coronary artery bypass grafting (CABG) in 1990 and chronic renal failure (baseline GFR: 45 ml/min/1.73 m 2 ) underwent a coronary angiography for a Non-ST segment elevation myocardial infarction (NSTEMI). Native coronary circulation was completely occluded at the proximal segments. Grafts angiography showed a tandem calcified lesions of SVG on distal right coronary artery (RCA) and an ostial stenosis of the SVG on first obtuse marginal branch (OM1). Left internal mammary artery on the mid left anterior descending artery was patent. Ad Hoc PCI of SVG on RCA was attempted. The proximal calcified stenosis has been crossed with a 1.5 x 12 mm balloon only with the support of Guidezilla™, however the non-compliant (NC) balloon 2.5 x 15 mm was unable to break the hard and calcified plaque. After several attempts, the procedure was interrupted with a suboptimal result. An elective transradial PCI of SVG on RCA with rotational atherectomy was performed. Two runs with 1.25 mm burr and 2 runs with 1.5 mm burr were carried out. Then, the use of distal anchoring balloon warranted support and tracking, made as centring rail for the advance of the tip of the "mother-and-child" catheter into the SVG. During slow deflation of the balloon, the Guidezilla™ was advanced distal to the stenoses to be stented, thus allowing the placement of two long drug eluting stents according to a LSD technique., Conclusions: Rotational atherectomy is a feasible option for non-dilatable stenoses in old SVGs when there is no evidence of thrombus or vessel dissection and the subsequent use of "mother-and-child" catheter has a key role, especially in case of radial approach, for long stents delivery.

Objective: Cardiac allograft vasculopathy (CAV) can be detected early with intravascular ultrasound (IVUS), but there is limited information on the most efficient imaging protocol., Methods: Coronary angiography and IVUS of the three coronary arteries were performed. Volumetric IVUS analysis was performed, and a Stanford grade determined for each vessel., Results: Eighteen patients were included 18 (range 12-24) months after transplantation. Angiographic CAV severity ranged from none (CAV0) to mild (CAV1), whereas IVUS CAV severity ranged from none (Stanford grade I) to severe (grade IV). Maximal intimal thickness measured with IVUS was significantly greater in the LAD (0.84 ± 0.48 mm) than in the LCX (0.46 ± 0.32 mm) or the RCA (0.53 ± 0.41 mm, P = .005). Diagnostic accuracy of IVUS in the left anterior descending artery was 100% (18 of 18 Stanford grades matched the patient's highest overall Stanford grade), 66% in the right coronary artery (12 of 18), and 56% in the left circumflex artery (11 of 18). The minimal required length of left anterior descending artery pullbacks to attain 100% accuracy was 36 mm (range 3-36 mm) distal from the guide catheter ostium., Conclusions: These data suggest that focal IVUS imaging of the proximal LAD followed by volumetric analysis may suffice when screening for transplant vasculopathy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: A new end point called ICD-resistant mortality was evaluated to assess the clinical efficacy of ICD implantations., Methods and Results: In 302 ICD patients with ischaemic cardiomyopathy, we investigated which clinical parameters predicted useful ICD implantations using cumulative incidence competing risk analysis. Implantation was deemed clinically useful when the ICD provided appropriate therapy and the patient survived implantation by 1 year and the first shock by 30 days. ICD-resistant mortality (ICDRM) was defined as death within 30 days after the first shock, within 1 year of implantation or without previous appropriate ICD therapy. After 5 years, ICDRM occurred in 23% of implantations, while 36% were clinically useful. After multivariable analysis, ICDRM was associated with LVEF <35% (HR: 2.63; p = .005), beta-blocker dose <50% (HR: 2.0; p = .01) and anterior or diffuse infarct location (HR: 3.61; p = .001 and HR: 2.89; p = .02). Useful ICD implantations were associated with beta-blocker dose <50% (HR: 1.64; p = .02) and non-anterior infarct location (HR: 3.22 vs anterior and 1.59 vs diffuse; combined p<.001)., Conclusions: Five years after implantation, an ICD could be classified as useful in 1 out of 3, while ICDRM occurred in one out of four patients. At 10 years, up to 80% of implantations could be categorized. Lower LVEF was related with significantly higher incidence of ICDRM. Anterior infarcts were associated with more ICDRM and less useful implantations than non-anterior infarcts. Future risk stratification for ICD should focus more on the discrimination between arrhythmic risk, probably preventable by ICDs and ICD-resistant mortality risk.

Background: A proportion of patients with an implantable cardioverter-defibrillator (ICD) in prevention of sudden cardiac death will only receive their first appropriate ICD therapy (AT) after device replacement. Clinical reassessment at the time of replacement could be helpful to guide the decision to replace or not in the future., Methods: All patients with an ICD for primary or secondary prevention in ischemic (ICM) or nonischemic cardiomyopathy were included in a single-center retrospective registry. The association of changes in left ventricular ejection fraction (LVEF; cut-off at 35%), worsening renal function (decrease in estimated glomerular filtration rate > 15 mL/min), and worsening New York Heart Association class at elective device replacement with mortality and AT was analyzed using adjusted Cox regression analysis., Results: A total of 238 (33%) out of 727 patients received elective device replacement (86.1% male, 74.4% ICM, 42.9% primary prevention). During this replacement 20.2% received a device upgrade. The mean time to replacement was 6.4 ± 2.0 years and mean follow-up after replacement was 3.4 ± 3.0 years. Of patients who did not receive AT before replacement 23.1% received their first AT after replacement. Worsening renal function (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.50-5.18) and a consistently LVEF ≤35% compared to a consistently LVEF >35% (HR 2.15, 95% CI 1.10-4.19) at the time of replacement were independent predictors of mortality. Independent predictors of first AT after replacement could not be identified., Conclusion: Although reassessment of LVEF and renal function at replacement can be helpful in predicting total mortality, the clinical utility to guide reimplantation seemed limited. Our experience indicates that approximately 25% of patients received their first AT only after replacement., (© 2017 Wiley Periodicals, Inc.)

Background: The correlation between angiographic assessment of coronary stenoses and fractional flow reserve (FFR) is weak. Whether and how risk factors impact the diagnostic accuracy of angiography is unknown. We sought to evaluate the diagnostic accuracy of angiography by visual estimate and by quantitative coronary angiography when compared with FFR and evaluate the influence of risk factors (RF) on this accuracy., Methods and Results: In 1382 coronary stenoses (1104 patients), percent diameter stenosis by visual estimation (DS VE ) and by quantitative coronary angiography (DS QCA ) was compared with FFR. Patients were divided into 4 subgroups, according to the presence of RFs, and the relationship between DS VE , DS QCA , and FFR was analyzed. Overall, DS VE was significantly higher than DS QCA ( P <0.0001); nonetheless, when examined by strata of DS, DS VE was significantly smaller than DS QCA in mild stenoses, although the reverse held true for severe stenoses. Compared with FFR, a large scatter was observed for both DS VE and DS QCA . When using a dichotomous FFR value of 0.80, C statistic was significantly higher for DS VE than for DS QCA (0.712 versus 0.640, respectively; P <0.001). C statistics for DS VE decreased progressively as RFs accumulated (0.776 for ≤1 RF, 0.750 for 2 RFs, 0.713 for 3 RFs and 0.627 for ≥4 RFs; P =0.0053). In addition, in diabetics, the relationship between FFR and angiographic indices was particularly weak (C statistics: 0.524 for DS VE and 0.511 for DS QCA )., Conclusions: Overall, DS VE has a better diagnostic accuracy than DS QCA to predict the functional significance of coronary stenosis. The predictive accuracy of angiography is moderate in patients with ≤1 RFs, but weakens as RFs accumulate, especially in diabetics., (© 2017 American Heart Association, Inc.)

Background: During thermodilution-based assessment of volumetric coronary blood flow, we observed that intracoronary infusion of saline increased coronary flow. This study aims to quantify the extent and unravel the mechanisms of saline-induced hyperemia., Methods and Results: Thirty-three patients were studied; in 24 patients, intracoronary Doppler flow velocity measurements were performed at rest, after intracoronary adenosine, and during increasing infusion rates of saline at room temperature through a dedicated catheter with 4 lateral side holes. In 9 patients, global longitudinal strain and flow propagation velocity were assessed by transthoracic echocardiography during a prolonged intracoronary saline infusion. Taking adenosine-induced maximal hyperemia as reference, intracoronary infusion of saline at rates of 5, 10, 15, and 20 mL/min induced 6%, 46%, 111%, and 112% of maximal hyperemia, respectively. There was a close agreement of maximal saline- and adenosine-induced coronary flow reserve (intraclass correlation coefficient, 0.922; P <0.001). The same infusion rates given through 1 end hole (n=6) or in the contralateral artery (n=6) did not induce a significant increase in flow velocity. Intracoronary saline given on top of an intravenous infusion of adenosine did not further increase flow. Intracoronary saline infusion did not affect blood pressure, systolic, or diastolic left ventricular function. Heart rate decreased by 15% during saline infusion ( P =0.021)., Conclusions: Intracoronary infusion of saline at room temperature through a dedicated catheter for coronary thermodilution induces steady-state maximal hyperemia at a flow rate ≥15 mL/min. These findings open new possibilities to measure maximal absolute coronary blood flow and minimal microcirculatory resistance., (© 2017 American Heart Association, Inc.)

Background: Clinical guidelines on implantable cardioverter defibrillator (ICD) therapy changed significantly in the last decades with potential inherent effects on therapy efficacy. We aimed to study therapy rates in time and the association between therapies and mortality., Methods: All patients receiving an ICD, primary and secondary prevention, were included in a single-center retrospective registry. Information on first appropriate and inappropriate therapies was documented. Dates of implant were divided in P1: 1996-2001, P2: 2002-2008, and P3: 2009-2014., Results: A total of 727 patients, 84.9% male-66.4% ischemic cardiomyopathy (ICM)-56% primary prevention-mean follow-up 5.2 ± 4.1 years, were included. There was a shift from secondary to primary prevention indications, from ischemic to non-ICM, and from single chamber to cardiac resynchronization therapy defibrillator devices. The annual 1- and 3-year appropriate shock (AS) rate declined from 29.4% and 15.1% in P1, over 13.3% and 9.2% in P2 to 7.8% and 5.7% in P3 (log-rank P < 0.001), while inappropriate shock (IAS) rates remained unchanged (log-rank P = 0.635). After multivariate regression analysis a higher age at implant, lower left ventricular ejection fraction, history of stroke, diabetes mellitus, intake of loop diuretics or digitalis, higher creatinine, and longer QTc were independent predictors of mortality., Conclusion: These changes in clinical practice with a shift to primary prevention and rise in non-ICM implants caused a significant decrease in AS incidence, while IAS remained stable. Receiving AS or IAS was not an independent predictor of mortality in our real-life cohort., (© 2016 Wiley Periodicals, Inc.)

Background: The fractional flow reserve (FFR) value of 0.75 has been validated against ischemic testing, whereas the FFR value of 0.80 has been widely accepted to guide clinical decision making. However, revascularization when FFR is 0.76 to 0.80, within the so-called gray zone, is still debatable., Methods and Results: From February 1997 to June 2013, all patients with single-segment disease and an FFR value within the gray zone or within the 2 neighboring FFR strata (0.70-0.75 and 0.81-0.85) were included. Study end points consisted of major adverse cardiovascular events (death, myocardial infarction, and any revascularization) up to 5 years. Of 17 380 FFR measurements, 1459 patients were included. Of them, 449 patients were treated with revascularization and 1010 patients were treated with medical therapy. In the gray zone, the major adverse cardiovascular events rate was similar (37 [13.9%] versus 21 [11.2%], respectively; P=0.3) between medical therapy and revascularization, whereas a strong trend toward a higher rate of death or myocardial infarction (25 [9.4] versus 9 [4.8], P=0.06) and overall death (20 [7.5] versus 6 [3.2], P=0.059) was observed in the medical therapy group. Among medical therapy patients, a significant step-up increase in major adverse cardiovascular events rate was observed across the 3 FFR strata, especially with proximal lesion location. In revascularization patients, the major adverse cardiovascular events rate was not different across the 3 FFR strata., Conclusions: FFR in and around the gray zone bears a major prognostic value, especially in proximal lesions. These data confirm that FFR≤0.80 is valid to guide clinical decision making., (© 2016 American Heart Association, Inc.)

Objectives: The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected., Background: Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose., Methods: In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 μg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Qmax, %)., Results: Q/Qmax did not increase significantly beyond dosages of 60 μg for the RCA and 160 μg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 μg in the RCA and was 15% after injection of 200 μg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 μg in the RCA and 21 ± 6 s after the injection of 200 μg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 μg of adenosine., Conclusions: This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 μg in the RCA and 200 μg in the LCA induces maximum hyperemia while being associated with minimal side effects., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: In high-risk patients, implantable cardioverter-defibrillators (ICDs) can convert the mode of death from arrhythmic to pump failure death. Therefore, we introduced the concept of 'ICD-resistant mortality' (IRM), defined as death (a) without previous appropriate ICD intervention (AI), (b) within 1 month after the first AI, or (c) within 1 year after the initial ICD implantation. Implantable cardioverter-defibrillator implantation in patients with a high risk of IRM should be avoided., Methods and Results: Implantable cardioverter-defibrillator patients with ischaemic heart disease were included if a digitized 24 h Holter was available pre-implantation. Demographic, electrocardiographic, echocardiographic, and 24 h Holter risk factors were collected at device implantation. The primary endpoint was IRM. Cox regression analyses were used to test the association between predictors and outcome. We included 130 patients, with a mean left ventricular ejection fraction (LVEF) of 33.6 ± 10.3%. During a follow-up of 52 ± 31 months, 33 patients died. There were 21 cases of IRM. Heart rate turbulence (HRT) was the only Holter parameter associated with IRM and total mortality. A higher New York Heart Association (NYHA) class and a lower body mass index were the strongest predictors of IRM. Left ventricular ejection fraction predicted IRM on univariate analysis, and was the strongest predictor of total mortality. The only parameter that predicted AI was non-sustained ventricular tachycardia., Conclusion: Implantable cardioverter-defibrillator implantation based on NYHA class and LVEF leads to selection of patients with a higher risk of IRM and death. Heart rate turbulence may have added value for the identification of poor candidates for ICD therapy. Available Holter parameters seem limited in their ability to predict AI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com.)

Introduction: There is convincing experimental evidence that cellular action potential duration (APD) alternans is arrhythmogenic but its relationship with body surface microvolt T-wave alternans (MTWA) remains unclear. We investigated the relationship between MTWA and APD alternans induced by alternating cycle length (CL) pacing in a pig model., Methods: In 10 pigs, catheters in the right atrium (RA) and right (RV) and left ventricle (LV) allowed pacing and recording of monophasic action potentials (MAP). During RA pacing at stable 500-ms CL, LV was paced at alternating CL (505 ms and 495 ms). Changing the alternating LV (A-LV) pacing delay changes the size of the region with alternating ventricular activation. Spectral analysis of intracardiac MAP was correlated with body surface MTWA. In a similar setup (during alternating pacing in RV and LV), we investigated concordant versus discordant APD alternans., Results: Pacing the LV with subtle alternating cycle lengths at short A-LV delay leads to broad QRS (97 ± 10 ms), body surface MTWA (mean Valt 4.2 ± 1.8 µV), and positive RR-interval alternans. At longer A-LV delay, not resulting in QRS widening (68 ± 5 ms), body surface RR alternans was absent but MTWA remained detectable and was even more pronounced (8.7 ± 5.1 µV, P < 0.01). During both concordant and discordant pacing MTWA was present. The precordial leads were better for detecting discordant APD alternans (8.0 ± 2.9 µV and 12.8 ± 4.52 µV, P = 0.02)., Conclusion: MTWA is a potent technique to detect subtle and isolated intracardiac APD alternans that is artificially induced by alternating pacing. In the same model, discordant activation alternans can only be discriminated from concordant when using a quantifying approach of MTWA analysis., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)