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Abstract Background A work accident constitutes a shock to health, likely to alter mental states and affect the use of psychotropic drugs. We focus on the use of benzodiazepines, which are a class of drugs commonly used to treat anxiety and insomnia. Prolonged use can lead to dependence. Our objective is to determine the extent to which work accidents lead to benzodiazepine use and overuse (i.e. exceedance of medical guidelines). Method We use a two-step selection model (the Heckman method) based on data from the French National Health Data System (Système National des Données de Santé, SNDS). Our study sample includes all general plan members who experienced a single work accident in 2016 (and not since 2007). This sample includes 350,000 individuals in the work accident group and more than 1.1 million people randomly drawn from the population without work accidents from 2007 to 2017 (the non-work accident group). Results The occurrence of a work accident leads to an increase in benzodiazepine use and overuse the following year. The selection model shows a clear influence of the accident on the use probability (+ 39%), but a very slight impact on the risk of overuse among users (+ 1.7%), once considered the selection effect. The effect on overuse risk is higher for more severe accidents and among women. Conclusion The increase in the risk of benzodiazepine overuse is due to an increase in the likelihood of using benzodiazepines after a work accident that leads to overuse, rather than an increase in likelihood of overuse among people who use benzodiazepines. Results call for targeting the first-time prescription to limit the risk of overuse after a work accident.

Abstract Coral reefs are severely threatened by global and local environmental changes. However, susceptibility to perturbations and subsequent mortality varies among coral species. In this study, we tested the contribution of genetic and environmental conditions to coral’s phenotypic response in Pocillopora spp. and Porites spp. sampled together at a large ecological and temporal scale throughout the Pacific Ocean. We assessed coral phenotype signatures using a multi-biomarker approach (animal and symbiont biomasses, protein carbonylation and ubiquitination and total antioxidant capacities). In both genera, we highlighted a strong anticorrelation between the redox state and the animal and symbiont biomasses. In addition, Pocillopora exhibited high phenotypic plasticity, responding to various environmental variables such as temperature, nutrients, phosphate, and carbonate chemistry. In contrast, Porites displayed more robust phenotypes influenced by both genetics and past climate events. In conclusion, co-located coral species display different phenotypic response strategies that are influenced by different environmental conditions.

The cnidarian-dinoflagellate symbiosis is a mutualistic intracellular association based on the photosynthetic activity of the endosymbiont. This relationship involves significant constraints and requires co-evolution processes, such as an extensive capacity of the holobiont to counteract pro-oxidative conditions induced by hyperoxia generated during photosynthesis. In this study, we analyzed the capacity of Anemonia viridis cells to deal with pro-oxidative conditions by in vivo and in vitro approaches. Whole specimens and animal primary cell cultures were submitted to 200 and 500 μM of H2O2 during 7 days. Then, we monitored global health parameters (symbiotic state, viability, and cell growth) and stress biomarkers (global antioxidant capacity, oxidative protein damages, and protein ubiquitination). In animal primary cell cultures, the intracellular reactive oxygen species (ROS) levels were also evaluated under H2O2 treatments. At the whole organism scale, both H2O2 concentrations didn’t affect the survival and animal tissues exhibited a high resistance to H2O2 treatments. Moreover, no bleaching has been observed, even at high H2O2 concentration and after long exposure (7 days). Although, the community has suggested the role of ROS as the cause of bleaching, our results indicating the absence of bleaching under high H2O2 concentration may exculpate this specific ROS from being involved in the molecular processes inducing bleaching. However, counterintuitively, the symbiont compartment appeared sensitive to an H2O2 burst as it displayed oxidative protein damages, despite an enhancement of antioxidant capacity. The in vitro assays allowed highlighting an intrinsic high capacity of isolated animal cells to deal with pro-oxidative conditions, although we observed differences on tolerance between H2O2 treatments. The 200 μM H2O2 concentration appeared to correspond to the tolerance threshold of animal cells. Indeed, no disequilibrium on redox state was observed and only a cell growth decrease was measured. Contrarily, the 500 μM H2O2 concentration induced a stress state, characterized by a cell viability decrease from 1 day and a drastic cell growth arrest after 7 days leading to an uncomplete recovery after treatment. In conclusion, this study highlights the overall high capacity of cnidarian cells to cope with H2O2 and opens new perspective to investigate the molecular mechanisms involved in this peculiar resistance.

Cnidarian primary cell cultures have a strong potential to become a universal tool to assess stress-response mechanisms at the cellular level. However, primary cell cultures are time-consuming regarding their establishment and maintenance. Cryopreservation is a commonly used approach to provide stable cell stocks for experiments, but it is yet to be established for Cnidarian cell cultures. The aim of this study was therefore to design a cryopreservation protocol for primary cell cultures of the Cnidarian Anemonia viridis, using dimethyl sulfoxide (DMSO) as a cryoprotectant, enriched or not with fetal bovine serum (FBS). We determined that DMSO 5% with 25% FBS was an efficient cryosolution, resulting in 70% of post-thaw cell survival. The success of this protocol was first confirmed by a constant post-thaw survival independently of the cell culture age (up to 45 days old) and the storage period (up to 87 days). Finally, cryopreserved cells displayed a long-term recovery with a maintenance of the primary cell culture parameters and cellular functions: formation of cell aggregates, high viability and constant cell growth, and unchanged intrinsic resistance to hyperthermal stress. These results will further bring new opportunities for the scientific community interested in molecular, cellular, and biochemical aspects of cnidarian biology.

Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings suggest that defects in dermo/epidermal interactions could contribute to BCC susceptibility in NBCCS patients.

En janvier 1507, les « apparitions de la Vierge » dans le couvent dominicain de Berne commencent à défrayer la chronique. L’affaire des visions de Jean Jetzer se déroule sur fond de querelle immaculiste entre dominicains et franciscains. Les dominicains du couvent de Berne ont eu l’idée de créer des apparitions de la Vierge de toutes pièces au moyen de déguisement et de machineries de théâtre pour faire croire à la conception maculée de Marie contre leurs détracteurs franciscains. Leur chef de file est le prieur du couvent, Johannes Vatter, assisté de trois autres accolytes, le sous-prieur, Franz Ueltschi, le maître en théologie et lecteur Stephan Boltzhurst, l’administrateur Heirich Steinegger. La machination qu’ils orchestrent érige de la sorte en visionnaire patenté un novice à la crédulité éprouvée, Jean Jetzer, victime de leur complot. L’affaire défie la chronique et provoque la rumeur. La ville de Berne où elle se déroule est toute proche de la Bâle du Concile (1431-1449) qui a déclaré l’Immaculée Conception « doctrine pieuse et conforme au culte de l’Église » (session du 17 septembre 1439) comme de la Bâle du Formicarius – somme démonologique de répression de la sorcellerie – composée en 1435-1437 par le prieur des dominicains, Jean Nider, sur la base des conclusions de l'inquisiteur Pierre de Berne. La « fiction » de Berne témoigne des stratégies théologiques à l’égard des révélations et des miracles dans la controverse de l’Immaculée Conception. Si elle relève ici de l’affabulation volontaire, elle montre aussi l’usage qui pouvait être fait du discours visionnaire et de son nécessaire discernement à la toute fin du Moyen Âge. L’ensemble de ce dossier exceptionnel permet dès lors de saisir l’instrumentalisation des révélations qui ont pris une importance nouvelle dans les querelles théologiques de l’Immaculée Conception à la fin du Moyen Âge.

BACKGROUND: High mobility group box 1 protein (HMGB1) is a major endogenous danger signal that triggers inflammation and immunity during septic and aseptic stresses. HMGB1 recently emerged as a key soluble factor in the pathogenesis of various infectious diseases, but nothing is known of its behaviour during herpesvirus infection. We therefore investigated the dynamics and biological effects of HMGB1 during HSV-2 infection of epithelial HEC-1 cells. METHODOLOGY/PRINCIPAL FINDINGS: Despite a transcriptional shutdown of HMGB1 gene expression during infection, the intracellular pool of HMGB1 protein remained unaffected, indicating its remarkable stability. However, the dynamics of HMGB1 was deeply modified in infected cells. Whereas viral multiplication was concomitant with apoptosis and HMGB1 retention on chromatin, a subsequent release of HMGB1 was observed in response to HSV-2 mediated necrosis. Importantly, extracellular HMGB1 was biologically active. Indeed, HMGB1-containing supernatants from HSV-2 infected cells induced the migration of fibroblasts from murine or human origin, and reactivated HIV-1 from latently infected T lymphocytes. These effects were specifically linked to HMGB1 since they were blocked by glycyrrhizin or by a neutralizing anti-HMGB1 antibody, and were mediated through TLR2 and the receptor for Advanced Glycation End-products (RAGE). Finally, we show that genital HSV-2 active infections also promote HMGB1 release in vivo, strengthening the clinical relevance of our experimental data. CONCLUSIONS: These observations target HMGB1 as an important actor during HSV-2 genital infection, notably in the setting of HSV-HIV co-infection.

Tetanus is a neurologic disorder caused by tetanospasmin, a protein toxin elaborated by Clostridium tetani. Cephalic tetanus is a localized form of the disease causing trismus and dysfunction of cranial nerves. We report the case of a man who presented with facial trauma, complete ophthalmoplegia, exophthalmos, areactive mydriasis, and periorbital hematoma. An orbital CT revealed air bubbles in the right orbital apex. The patient was given a tetanus toxoid booster and antibiotherapy. After extraction of a wooden foreign body, the patient developed right facial nerve palsy, disorders of swallowing, contralateral III cranial nerve palsy, and trismus. Only one case of cephalic tetanus from penetrating orbital wound has been reported in literature 20 years ago. When a patient presents with an orbital wound with ophthalmoplegia and signs of anaerobic infection, cephalic tetanus should be ruled out.

Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1(+/-) genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients.

The article aims to highlight the particularities of photomontage as a representation of the architectural project, using photography as a supporting image. It develops an image analysis of a photomontage produced by the architects Lacaton & Vassal in the context of the competition for the construction of the FRAC Grand-Large, in Dunkirk, France, 2009. Through this examination, the following issues are addressed: the indiciality of the photographs used as a support for the photomontages, the way in which the image registers deployed by a photomontage can be presented as embodiments of an architectural project. Thus, the images become both representations and metaphors of the project, capable of serving the architects’ purpose.

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue Economique is the property of Fondation Nationale des Sciences Politiques and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives The purpose of this study was to assess the possible effect of residual myocardial ischaemia on induced ventricular arrhythmia during programmed ventricular stimulation in survivors of a first acute myocardial infarction.Background Most deaths after hospital discharge for acute myocardial infarction are sudden and presumably arrhythmic. Sudden cardiac death results from a dynamic interaction of structural abnormalities and transient triggering factors. The role of myocardial ischaemia as a trigger for ventricular arrhythmias remains unclear. We hypothesized that residual myocardial ischaemia after a first acute myocardial infarction is a potent trigger for sustained ventricular tachyarrhythmias, particularly in the presence of an abnormal myocardium.Methods and Results In this prospective study, programmed electrical stimulation, coronary angiography and dipyridamole-thallium-201 scintigraphy single-photon emission computed tomography were performed in 90 consecutive survivors of a first acute myocardial infarction. Patients, divided in two groups—group 1 with induced ventricular tachyarrhythmia (n=24) and group 2 without induced ventricular tachyarrhythmia (n=66)—were compared regarding residual myocardial ischaemia. The two groups were comparable in terms of mean left ventricular ejection fraction, infarct size and location, gender ratio, peak creatine kinase value, and extent of coronary disease. Residual myocardial ischaemia was detected in 32 patients: 15 (42·5%) belonged to group 1 and 17 (25·7%) to group 2. There was a statistically significant difference between the two groups regarding the presence and the extent of residual myocardial ischaemia (P<0·05).Conclusion Residual myocardial ischaemia, revealed by dipyridamole-thallium-201 scintigraphy following a first acute myocardial infarction, might contribute to electrical instability evaluated by programmed ventricular stimulation. [ABSTRACT FROM PUBLISHER]

Introduction: T wave morphological changes before onset of ventricular arrhythmia are poorly known. ICD-stored intracardiac electrograms (EGM) present a unique opportunity for detecting temporal changes in repolarisation before initiation of VT/VF. Methods: 57 implanted patients with St Jude Medical ICDs (45 men, 64±12 yo, mean EF 34±15%) were prospectively enrolled. Eleven different T wave parameters were extracted from EGM (T amplitude, T peak time, T end time, T duration between baseline crossing and between points of maximal slopes, T peak to T end, maximal ascending and descending slopes, timing of points of maximal slopes and T wave area). Values of each parameter in recordings prior to VT/VF were compared to control recordings sharing comparable QRS and T wave morphology and similar heart rate in the same pts. Results: 23 VT/VF episodes (24±13 beats) and 13 baseline (25±9 beats) (ns) were analyzed in 12 pts (1,9 episode/pt). Mean heart rate was 71±17 bpm for episodes and 66±16 bpm for baseline recordings (ns). Significant differences were found in T wave amplitude, T wave maximal slopes, T peak time and timing of the T wave maximal ascending slope (although ns when corrected by the heart rate). Conclusions: T wave amplitude is higher, T wave slopes are steeper and initial parts of the T wave are earlier before ventricular arrhythmia compared to baseline. Detection of T wave changes prior to VT/VF might be useful in predicting imminent arrhythmia occurrence. Display Omitted [ABSTRACT FROM AUTHOR]

Introduction: T wave morphological changes before onset of ventricular arrhythmia are poorly known. ICD-stored intracardiac electrograms (IEGM) present a unique opportunity for detecting temporal changes in repolarisation before initiation of VT/VF. Methods: 56 implanted patients with St Jude medical ICDs (44 men, 63±12 yo, mean EF 34±15%) were prospectively enrolled. Eleven different T wave parameters were extracted from IEGM (T amplitude, T peak time, T end time, T duration between baseline crossing and between points of maximal slopes, T peak to T end, maximal ascending and descending slopes, timing of points of maximal slopes and T wave area). Averaged values of each parameter in recordings prior to VT/VF were compared to control recordings sharing comparable QRS and T wave morphology and similar heart rate in the same pts. Results: 22 VT/VF episodes (24±13 beats) and 13 baseline (25±9 beats) (ns) were analyzed in 12 pts (1,8 episode/ pt). Mean heart rate was 71±17 bpm for episodes and 66±16 bpm for baseline recordings (ns). Significant differences were found in T wave amplitude and slopes. Durations and timings of the different parts of the T wave did not significantly vary. Conclusions: Detection of T wave changes prior to VT/VF might be useful in predicting imminent arrhythmia occurrence. T wave amplitude is higher and T wave slopes are steeper before ventricular arrhythmia compared to baseline, without significant shortening of different repolarisation times. Display Omitted [Copyright &y& Elsevier]

Objective Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of thromboembolic events or other complications. The French randomized, multicenter, SETAM trial assessed the impact of the home monitoring (HM) technology on detection and treatment of supra-ventricular arrhythmia (SVA). Methods Patients (pts) implanted with a dual chamber pacemaker were enrolled in the study at hospital discharge if they had a sinusal rhythm at enrollment, no antiarrhythmic, anticoagulant or dual-antiplatelet therapy, and if they had a CHA2DS2-VASc score of 2 or more. The pts were randomly assigned to an active group (Act Gp), followed by Biotronik HM, or a control group (Cont Gp) without HM surveillance. The time from implantation to the first SVA-related intervention was compared between the 2 groups (primary endpoint). Results A total of 595 pts (mean age = 79±8 y.o, 63% male, mean CHA2DS2-VASc score = 3.7±1.2) were followed during 12.8±3.3Mo. The most prevalent co-morbidities were hypertension (82% pts), diabetes (29%) and vascular disease (24%). Implantation indications were atrio-ventricular blocks in 77% of pts, sinus node disease in 20% and others in 3%.The global SVA incidence was 25% (29% in the Act Gp vs 22% in the Cont Gp, p=ns).A therapy (drugs or ablation) was instituted for 49/291 pts (17%) in the Act Gp vs 43/304 pts (14%) in the Cont Gp (p=ns). The median time from implantation to the first therapy for SVA was 114 [44; 241] days in the Act Gp vs 224 [67; 366] days in the Cont Gp, representing a median gain of 110-days in SVA management (50% reduction, p=0.01). Over these 92 pts, 54 had AF (59%) and 38 had atrial flutter or tachyarrhythmia (41%). Anticoagulation was initiated in 80% of pts and antiarrhythmic drugs in 55%. Conclusion The SETAM study demonstrated that HM allows earlier detection and treatment of SVA in pacemaker pts. The next step is to report how early detection of SVA with HM can possibly improve the patients clinical outcome. [ABSTRACT FROM AUTHOR]

Introduction We developed the usage of a simple tunnelling method from controlateral access to the device in case of homolatéral subclavian access failure when an additional lead is needed. Goal of the study long term evaluation of feasibility and safety of this tunneling strategy. Method From September 1998 to September 2011, a coronary sinus (CS) lead was implanted through controlateral access after failure of homolateral to the device implantation in 31 consecutive patients (19 males 72+/- 8 yo). Indications were thrombosis 14 and failure to catheterize CS 17. All these patients were already implanted with a single or double chamber pacemaker or internal cardiac defibrillator and were referred for upgrading to biventricular pacing. The packaging sheath of a simple conventional catheter (plastimed) was introduced from one side to the other under local anesthesia after scissors dissection under local anesthesia. Tunneling of coronary sinus lead was performed through the sheath which was then withdrawed. Results Success tunneling procédure rate was 100%. Tunelling time was 3+/-2 mn. Complications related to the procedure: 2 cases of xylocaine overdose needed temporary ventilation assistance at beginning of experience. 1 early dislodgment needed replacement, 2 cases of early battery wear because of low impédance of the cs lead. No hematoma, no acute or late pain complain, no lead infection were reported. Conclusion Controlateral implantation through a simple packaging sheath is a simple and safe option in case of homolateral access failure in upgrading indications. [ABSTRACT FROM AUTHOR]

Background: The French study OBEPI in 2006 showed that around 1 person out of 3 is overweight (BMI>25) or obese (BMI>30). In Coronary Rehabilitation (CR) in Joigny (France), we observed that more than 2 persons out of 3 are overweight or obese (n=110). The objectives of CR are the improvements of life expectancy, the quality of life. But in practice, how does the body composition evolve? Methods: CR consists of 20 sessions from 9 am till 4 pm, 3 times a week. At first and after CR, patients performed a symptom limited cardiopulmonary test and a 6 minutes walking test: the bioelectrical impedance was done on a Tanita BC 418. Every session includes physical training (ergocycle, walk, strength training: 45 min each), therapeutic education, in particular dietary (information and therapeutic cooking) minimum once a week. Results: The patient''s physical performances are improved (P<0,01): VO2 peak (+0,15L/min) and distance covered during 6MWT (+86m). The weight is stable but we observe that the fat mass (FM) decreases of 717g (P<0,01) for an increase of the lean body mass (LBM) of 812g (P<0,01). Conclusion: Multidisciplinary CR allows an improvement of physical performances. The remodelling of body composition results in an increase of LBM and a decrease of FM. It seems that an estimation of the body composition is useful in order to quantize exactly the weight evolution and these components during a CR. [Copyright &y& Elsevier]

Introduction: T wave alternans (TWA) has been demonstrated as a strong predictor of mortality and ventricular arrhythmias. ICD-stored intracardiac electrograms (IEGM) present a unique opportunity for detecting temporal relationship between the occurrence of TWA and spontaneous arrhythmia. The aim of the ETWAS study was to assess the feasibility of detection of TWA preceding the onset of VT/VF in IEGM. Methods: 56 implanted patients with St Jude medical ICDs (44 men, 63±12 yo, mean EF 34±15%) were prospectively enrolled and monitored for one year. Thirteen different T wave parameters were extracted from IEGM (T amplitude, T peak time, Bazett and Hodges corrected T peak time, T end time, T duration between baseline crossing and between points of maximal slopes, T peak to T end, maximal ascending and descending slopes, timing of points of maximal slopes and T wave area). Successive beat by beat differences in each parameter in recordings prior to VT/VF were compared to control recordings in the same pts. TWA was considered if beat by beat variations for at least one parameter was significantly higher than baseline with a p value < 0,01. Results: 22 VT/VF episodes (24±13 beats, 71±17 bpm) and 13 baseline (25±9 beats, 72±18) (ns) were analyzed in 12 pts (1,8 episode/ pt). TWA was present before VT/VF onset in 13 episodes (7 pts) with 1 to 9 differing parameters (3±2). Significant beat by beat differences before VT/VF onset were observed in amplitude, timing, slopes, area and duration of the T wave. Amplitude of the beat by beat variations was 3 to10 larger in episodes than in baseline. Paired and unpaired comparisons of the averaged values of beat by beat variations however did not reveal significant difference between baseline and episodes, except for T wave amplitude (0,07 +/– 0,006 vs 0,14 +/– 0,03 mV, p=0.03 paired and 0,04 unpaired). Conclusions: Detection of TWA prior to VT/VF might be useful in predicting imminent arrhythmia occurrence. TWA can be detected before VT/VF onset in more than half of episodes using a simple time-domain technique and multiple T wave measurements. T wave amplitude seems the most discriminant parameter. [Copyright &y& Elsevier]

Aims: To assess whether abnormal dobutamine stress echocardiography (DSE) can be a consequence of dobutamine-induced coronary spasm in patients with angiographically documented vasospastic coronary arteries. Methods: Between January 2004 and April 2008, we prospectively evaluated all patients with known or suspected coronary artery disease (CAD) referred to the echocardiography laboratory for dobutamine stress tests (6061 examinations). Those with abnormal DSE underwent coronary angiogram with a systematic methylergometrine intracoronary injection in the case of absence of significant coronary stenosis or spontaneous occlusive coronary spasm. Patients who had spontaneous occlusive coronary spasm or positive methylergometrine test, but no significant stenoses, were ultimately included in this study. Results: About 581 patients had abnormal DSE, among them only 20 (3.4%) fulfilled the inclusion criteria. There were 15 males and 5 females, and mean age was 64.35 years (range 52-85); 8 patients had a known history of CAD and all of them had at least two established cardiovascular risk factors. The culprit vessel was the left anterior descending artery in 10 cases (50%), right coronary artery in 8 cases (40%), and left circumflex in 2 cases (10%). There was a systematic correspondence between the culprit arteries and dobutamine-induced wall motion abnormality territories. No complications occurred during examination or during the provocation test. All the patients were discharged with a calcium channel blocker and were doing well after 13 months of mean follow-up. Conclusion: Coronary artery spasm can be induced at DSE, but is a rare finding; it could, though, be clinically relevant as it may partly explain some erroneously labelled ‘false-positive’ examinations. Methylergometrine provocation test is a safe and advisable approach in such situations. [Copyright &y& Elsevier]

Background: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates., Objectives: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD., Methods: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year., Results: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02)., Conclusions: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555)., Competing Interests: Funding Support and Author Disclosures This work was supported by an academic grant (Programme Hospitalier de Recherche Clinique National) from the French Government, and the Hospices Civils de Lyon was the academic sponsor, involved in the collection and verification of all the study data. St Jude Medical and Volcano provided 46% of fractional flow reserve wires without any charge. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Spontaneous reanalyzed coronary thrombus (SRCT) has been reported in autopsy series, but little is known about SRCT, and it is potentially under-diagnosed in clinical practice.Methods and Results:SRCT identified on OCT were included in a French multicenter series, the Lotus Root French Registry. A total of 34 SRCT were identified on OCT in 33 patients (23 male; median age, 56 years; IQR, 52-65 years); 23/33 patients (70%) presented with angina pectoris and/or dyspnea. Three angiographic aspects were distinguished retrospectively: braided, pseudo-dissected, and hazy. Stenosis severity on quantitative coronary analysis varied between 11% and 100% (median, 45%), whereas the reduction in lumen area on OCT varied between 20% and 92% (median, 68%). A typical "lotus root" aspect was confirmed on OCT, consisting of multiple circular concave-edged channels of varying size, numbering between 3 and 12 depending on the slice, separated by smooth-edged septa of high luminosity without posterior attenuation. OCT also served to guide treatment, with stenting in 91% of cases. During the 17-month follow-up 91% of patients had excellent evolution. One death and 3 ACS events occurred., Conclusions: In this large SRCT cohort, angiography had limited diagnostic value whereas OCT could be used to define disease characteristics and guide treatment of lesions inducing angina pectoris and/or silent myocardial ischemia. OCT-guided management was associated with good prognosis.

Aims: Angiography has limited value for identifying the causes of stent thrombosis (ST). We studied a large cohort of patients by optical coherence tomography (OCT) to explore ST characteristics and mechanisms., Methods and Results: A prospective multicentre registry was screened for patients with confirmed ST. Optical coherence tomography was performed after initial intervention to the culprit lesion (in 69% of cases in a deferred procedure). Stent thrombosis was classified as acute (AST), sub-acute (SAST), late (LST), and very late (VLST). Optical coherence tomography records were analysed in a central core lab. The analysis included 120 subjects aged 61.7 [51.4-70.7]; 89% male. Very late ST was the clinical presentation in 75%, LST in 6%, SAST in 15%, and AST in 4% of patients. Bare metal stents (BMS) were used in 39%, drug-eluting stents (DES) in 59% and bioresorbable vascular scaffolds in 2% of the cases. Optical coherence tomography identified an underlying morphological abnormality in 97% of cases, including struts malapposition (34%), neoatherosclerotic lesions (22%), major stent underexpansion (11%), coronary evagination (8%), isolated uncovered struts (8%), edge-related disease progression (8%), and neointimal hyperplasia (4%). Ruptured neoatherosclerotic lesions were more frequent with BMS than with DES (36 vs. 14%, P = 0.005), whereas coronary evaginations were more frequent with DES than with BMS (12 vs. 2%, P = 0.04). LST + VLST were mainly related to malapposition (31%) and neoatherosclerosis (28%), while prominent mechanisms for AST + SAST were malapposition (48%) and underexpansion (26%)., Conclusion: In patients with confirmed ST, OCT imaging identified an underlying morphological abnormality in 97% of cases., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography., Methods and Results: The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P=0.75). Reclassification safety was preserved in high-risk patients., Conclusion: This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

Objectives: The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events., Background: Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y(12)-adenosine diphosphate receptor with a higher potency on PR., Methods: A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month., Results: Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70)., Conclusions: Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patency of infarct-related artery in patients who suffered an acute myocardial infarction (AMI) has been shown to be associated with improved survival. Ventricular tachyarrhythmias induced by programmed electrical stimulation may be predictive of arrhythmic events and sudden death., Hypothesis: The study was undertaken to assess the possible effect of a patent infarct-related coronary artery on induced ventricular tachyarrhythmias during programmed ventricular stimulation in survivors of AMI., Methods: In this prospective study, programmed electrical stimulation was performed before hospital discharge (14 +/- 2 days) in 79 patients who survived an AMI. Patients were subdivided into two groups: Group I with patent infarct-related coronary artery (n = 64) and Group 2 with occluded infarct-related artery (n = 15) at coronary angiography performed at 14 +/- 2 days. These two groups were comparable in terms of mean left ventricular ejection fraction, location of infarct-related artery, number of diseased vessels, peak creatine kinase value, and infarct location., Results: Ventricular arrhythmias were induced in 21 patients ( 32.6%) of Group I and 4 patients (26.6%) of Group 2. This difference was not statistically significant., Conclusion: This study suggests that ventricular arrhythmias induced by programmed ventricular stimulation in survivors of AMI did not differ whether the infarct-related artery was patent or occluded. Other factors may play a role in electrical instability as assessed by programmed ventricular stimulation.