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Aims: Aortic valve calcification (AVC) of surgical valve bioprostheses (BPs) has been poorly explored. We aimed to evaluate in vivo and ex vivo BP AVCs and its prognosis value., Methods and Results: Between 2011 and 2019, AVC was assessed using in vivo computed tomography (CT) in 361 patients who had undergone surgical valve replacement 6.4 ± 4.3 years earlier. Ex vivo CT scans were performed for 37 explanted BPs. The in vivo CT scans were interpretable for 342 patients (19 patients [5.2%] were excluded). These patients were 77.2 ± 9.1 years old, and 64.3% were male. Mean in vivo AVC was 307 ± 500 Agatston units (AU). The AVC was 562 ± 570 AU for the 183 (53.5%) patients with structural valve degeneration (SVD) and 13 ± 43 AU for those without SVD (P < 0.0001). In vivo and ex vivo AVCs were strongly correlated (r = 0.88, P < 0.0001). An in vivo AVC > 100 AU (n = 147, 43%) had a specificity of 96% for diagnosing Stage 2-3 SVD (area under the curve = 0.92). Patients with AVC > 100 AU had a worse outcome compared with those with AVC ≤ 100 AU (n = 195). In multivariable analysis, AVC was a predictor of overall mortality (hazard ratio [HR] and 95% confidence interval = 1.16 [1.04-1.29]; P = 0.006), cardiovascular mortality (HR = 1.22 [1.04-1.43]; P = 0.013), cardiovascular events (HR = 1.28 [1.16-1.41]; P < 0.0001), and re-intervention (HR = 1.15 [1.06-1.25]; P < 0.0001). After adjustment for Stage 2-3 SVD diagnosis, AVC remained a predictor of overall mortality (HR = 1.20 [1.04-1.39]; P = 0.015) and cardiovascular events (HR = 1.25 [1.09-1.43]; P = 0.001)., Conclusion: CT scan is a reliable tool to assess BP leaflet calcification. An AVC > 100 AU is tightly associated with SVD and it is a strong predictor of overall mortality and cardiovascular events., Competing Interests: Conflict of interest: T.L.T. and J.-Christ R. received a basic research grant from Abbott-St Jude company dedicated to a mitral valve prolapse project. The other authors have no disclosure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Pre-stenting of the right ventricular outflow tract (RVOT) is commonly performed before percutaneous pulmonary valve implantation (PPVI), to relieve obstruction, prevent valved stent fractures, and provide a landing zone. This study aimed to evaluate the biomechanical characteristics of the stents currently used to perform pre-stenting of the RVOT., Methods: We assessed five commercially available stents: Cheatham-Platinum Stent ("CP Stent"), AndraStent XL, AndraStent XXL, Optimus XL, and Optimus XXL. Following stent deployment at nominal pressure, radial and longitudinal elastic recoils and radial resistance were measured. The bending stiffness of the stents crimped onto the balloons was also evaluated., Results: Three samples were tested for each stent. Our study showed no significant difference between the stent platforms in terms of radial elastic recoil, which was relatively low (< 10%). The longitudinal elastic recoil was also low for all the devices (< 5%). Significant differences were observed in radial resistance (P < 0.001). CP Stent and AndraStent XL exhibited the highest radial resistances. The bending stiffnesses of the stents crimped on their balloons were significantly different (P < 0.00001). Optimus XL and XXL were more flexible than the other stents., Conclusion: This study highlights the significant differences between the stents currently used in RVOT pre-stenting. Stents with good radial resistance are preferred, especially for calcified vessels, and flexibility is crucial for tortuous vessels. We proposed an algorithm for selecting the most suitable stent according to the need for radial force and flexibility, which will help inform clinicians considering RVOT revalvulation., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background and Aims: Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI., Methods: Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries., Results: Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29 mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively., Conclusions: Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aim: Few questionnaires are available for routine assessment of dyspnea. The study aimed to design a self-administered questionnaire assessing the impact of chronic dyspnea on daily activities, named DYSLIM (Dyspnea-induced Limitation)., Methods: The development followed 4 steps: 1: selection of relevant activities and related questions (focus groups); 2: clinical study: internal and concurrent validity vs. modified Medical Research Council (mMRC), Baseline Dyspnea Index (BDI) and Saint George Respiratory Questionnaire (SGRQ); 3: item reduction; 4: responsiveness. Eighteen activities (from eating to climbing stairs) were considered with 5 modalities for each: doing the task slowly, taking breaks, seeking assistance, changing habits, and activity avoidance. Each modality was graded from 5 (never) to 1 (very often). Validation study included 194 patients: COPD (FEV1 ≥ 50% pred: n = 40; FEV1 < 50% pred: n = 65); cystic fibrosis (n = 30), interstitial lung disease (n = 30), pulmonary hypertension (n = 29). Responsiveness was evaluated by post-pulmonary rehabilitation data in 52 COPD patients., Results: Acceptability was high and short term (7 days) reproducibility was satisfactory (Kappa mostly above 0.7). Concurrent validity was high vs. mMRC (Spearman correlation coefficient, r = 0.71), BDI (r = - 0.75) and SGRQ (r = - 0.79). The reduced questionnaire with 8 activities (from cleaning to climbing stairs) and 3 modalities (slowly, seeking help, changing habits) showed a comparable validity and was chosen as the final short version. Effect size of rehabilitation was good for both the full (0.57) and short (0.51) versions. A significant correlation was also found between changes of SGRQ and DYSLIM post rehabilitation: r = - 0.68 and r = - 0.60 for full and reduced questionnaires, respectively., Conclusion: The DYSLIM questionnaire appears promising for the evaluation of dyspnea-induced limitations in chronic respiratory diseases and seems suitable for use in various contexts., Competing Interests: Declaration of competing interest No Conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Multiple system atrophy (MSA) is a sporadic adult-onset rare neurodegenerative synucleinopathy for which counteracting central nervous system insulin resistance bears the potential of being neuroprotective. G-protein-(heterotrimeric guanine nucleotide-binding protein)-coupled receptor kinase 2 (GRK2) is emerging as a physiologically relevant inhibitor of insulin signaling., Objectives: We tested whether lowering brain GRK2 abundance may reverse insulin-resistance., Methods: We lowered brain GRK2 abundance through viral-mediated delivery of a GRK2-specific miRNA and quantified the reversion of a developing or an established insulin-resistant phenotype using the transgenic PLP-SYN mouse model of MSA., Results: Viral vector delivery of a GRK2 miRNA demonstrated a neuroprotective capacity when administered (1) in utero intracerebroventricularly in developing PLP-SYN mice and (2) intrastriatally in adult PLP-SYN mice. Decreased striatal GRK2 levels correlated in both designs with neuroprotection of the substantia nigra dopamine neurons, reduction in high-molecular-weight species of α-synuclein, and reduced insulin resistance., Conclusions: These data support GRK2 as a potential therapeutic target in MSA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Pediatric patients with congenital heart disease (CHD) often undergo low dose ionizing radiation (LDIR) from cardiac catheterization (CC) for the diagnosis and/or treatment of their disease. Although radiation doses from a single CC are usually low, less is known about the long-term radiation associated cancer risks. We aimed to assess the risk of lympho-hematopoietic malignancies in pediatric CHD patients diagnosed or treated with CC. A French cohort of 17,104 children free of cancer who had undergone a first CC from 01/01/2000 to 31/12/2013, before the age of 16 was set up. The follow-up started at the date of the first recorded CC until the exit date, i.e., the date of death, the date of first cancer diagnosis, the date of the 18th birthday, or the 31/12/2015, whichever occurred first. Poisson regression was used to estimate the LDIR associated cancer risk. The median follow-up was 5.9 years, with 110,335 person-years. There were 22,227 CC procedures, yielding an individual active bone marrow (ABM) mean cumulative dose of 3.0 milligray (mGy). Thirty-eight incident lympho-hematopoietic malignancies were observed. When adjusting for attained age, gender and predisposing factors to cancer status, no increased risk was observed for lympho-hematopoietic malignancies RR /mGy = 1.00 (95% CI: 0.88; 1.10). In summary, the risk of lympho-hematopoietic malignancies and lymphoma was not associated to LDIR in pediatric patients with CHD who undergo CC. Further epidemiological studies with greater statistical power are needed to improve the assessment of the dose-risk relationship., (© 2023. Springer Nature B.V.)

Endometrial ablation can be performed using a variety of techniques, including resectoscopic or non-resectoscopic approaches. In this study, we compared 2 resectoscopic endometrial ablation techniques. The first technique was rollerball coagulation followed by endometrectomy (type A; n = 103), and the second was the reverse (type B; n = 107). Besides excessive bleeding in 4 cases, the procedures were uneventful in both groups of patients. We did not encounter uterine perforation or cervical laceration. Satisfaction rates were 97% and 99% with an overall hysterectomy rate of 2.9%. These results compared favorably with those in the literature. The results of our study show that hysteroscopic endometrectomy is effective with few associated complications., (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

In the French region of Brittany, mainly in the department of the Côtes d'Armor, during the first half of 2021, seropositivity for SARS-CoV-2 was detected in five wild mustelids out of 33 animals tested (15.6%). Anti-SARS-CoV-2 IgG was detected against at least four out of five recombinant viral proteins (S1 receptor binding domain, nucleocapsid, S1 subunit, S2 subunit and spike) in three pine martens (Martes martes) and in two badgers (Meles meles) using the automated western blot technique. An ELISA test also identified seropositive cases, although these did not align with western blot results. Although the 171 qPCRs carried out on samples from the 33 mustelids were all negative, these preliminary results from this observational study nevertheless bear witness to infections of unknown origin. The epidemiological surveillance of Covid-19 in wildlife must continue, in particular with effective serology tools., (© 2022 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)

The Fontan operation represents the last of multiple steps that are offered a wide range of congenital cardiac lesions with a single ventricle (SV) physiology. Nowadays this surgical program consists of a total cavopulmonary connection (TCPC), by anastomosing systemic veins to the pulmonary arteries (PAs), excluding the right-sided circulation from the heart. As a result of imaging, surgical, percutaneous, and critical care improvements, survival in this population has steadily increased. However, the Fontan physiology chronically increases systemic venous pressure causing systemic venous congestion and decreased cardiac output, exposing patients to the failure of the Fontan circulation (FC), which is associated with a wide variety of clinical complications such as liver disease, cyanosis, thromboembolism, protein-losing enteropathy (PLE), plastic bronchitis (PB), and renal dysfunction, ultimately resulting in an increased risk of exercise intolerance, arrhythmias, and premature death. The pathophysiology of the failing Fontan is complex and multifactorial; i.e., caused by the single ventricle dysfunction (diastolic/systolic failure, arrhythmias, AV valve regurgitation, etc.) or caused by the specific circulation (conduits, pulmonary vessels, etc.). The treatment is still challenging and may include multiple options and tools. Among the possible options, today, interventional catheterization is a reliable option, through which different procedures can target various failing elements of the FC. In this review, we aim to provide an overview of indications, techniques, and results of transcatheter options to treat cavopulmonary stenosis, collaterals, impaired lymphatic drainage, and the management of the fenestration, as well as to explore the recent advancements and clinical applications of transcatheter cavopulmonary connections, percutaneous valvular treatments, and to discuss the future perspectives of percutaneous therapies in the Fontan population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jalal, Gewillig, Boudjemline, Guérin, Pilati, Butera, Malekzadeh-Milani, Avesani and Thambo.)

Background: In the MITRA-FR trial, transcatheter mitral valve repair (TMVR) was not associated with a 2-year clinical benefit in patients with secondary mitral regurgitation (SMR)., Aims: This landmark analysis aimed at investigating a potential reduction of the hospitalisation rate for heart failure (HF) between 12 and 24 months after inclusion in the MITRA-FR trial in patients randomised to the intervention group (TMVR with the MitraClip device), as compared with patients randomised to the control group (guideline-directed medical therapy [GDMT])., Methods: The MITRA-FR trial randomised 307 patients with SMR for TMVR on top of GDMT (TMVR group; n=152) or for GDMT alone (control group; n=155). We conducted a 12-month landmark analysis in surviving patients who were not hospitalised for HF within the first 12 months of follow-up. The primary endpoint was the 1-year cumulative number of HF hospitalisations., Results: A total of 140 patients (TMVR group: 67; GDMT group: 73) were selected for this landmark analysis with similar characteristics at inclusion in the trial. The primary endpoint was 28 events per 100 patient-years in the TMVR group, as compared with 60 events per 100 patient-years in the GDMT group (hazard ratio [HR] 0.46, 95% confidence interval [CI]: 0.20-1.02; p=0.057)., Conclusions: In this landmark analysis of the MITRA-FR trial, the cumulative rate of HF hospitalisation between 12 and 24 months among patients treated with TMVR on top of GDMT was approximately half as many as those of patients treated with GDMT alone, a difference which did not reach statistical significance in the setting of a low number of events.

We analyzed the epitope evolution of the spike protein in 1,860,489 SARS-CoV-2 genomes. The structural dynamics of these epitopes was determined by molecular modeling approaches. The D614G mutation, selected in the first months of the pandemic, is still present in currently circulating SARS-CoV-2 strains. This mutation facilitates the conformational change leading to the demasking of the ACE2 binding domain. D614G also abrogated the binding of facilitating antibodies to a linear epitope common to SARS-CoV-1 and SARS-CoV-2. The main neutralizing epitope of the N-terminal domain (NTD) of the spike protein showed extensive structural variability in SARS-CoV-2 variants, especially Delta and Omicron. This epitope is located on the flat surface of the NTD, a large electropositive area which binds to electronegatively charged lipid rafts of host cells. A facilitating epitope located on the lower part of the NTD appeared to be highly conserved among most SARS-CoV-2 variants, which may represent a risk of antibody-dependent enhancement (ADE). Overall, this retrospective analysis revealed an early divergence between conserved (facilitating) and variable (neutralizing) epitopes of the spike protein. These data aid in the designing of new antiviral strategies that could help to control COVID-19 infection by mimicking neutralizing antibodies or by blocking facilitating antibodies.

Rescue transcatheter aortic valve replacement (TAVR) in patients with cardiogenic shock is challenging, and there is limited literature on these critical patients. The aim of this study was to determine the characteristics and outcomes of patients undergoing TAVR, feasibility and safety of the procedure, and 1-year mortality factors. Thirty-eight patients with severe aortic disease and cardiogenic shock admitted to two French hospitals from 2015 to 2019 were included. The patients were critical, 78.9% of them had a left ventricular ejection fraction of <30%, and all of them received inotropic support. "Valve-in-valve" procedures were performed in 15.8% and 13.2% underwent balloon aortic valvuloplasty before TAVR. Edwards Sapien3® and Medtronic CoreValve EvolutR® were used. The survival probability remained reasonable for patients with cardiogenic shock who underwent rescue TAVR. The 30-day mortality rate was 7.9% and 21.1% at 1 year. No patient died during the intervention. The procedure was safe, with few complications except for acute kidney failure, the development of a left bundle branch block, and the need for pacemaker implantation. Both functional and echocardiographic results were good at 1 year, although 29% of the patients underwent rehospitalization within 1 year. The development of a left bundle branch block was found to be a mortality risk factor. This procedure is a safe and effective therapy with acceptable survivorship in critically ill patients. The benefits to their quality of life should be evaluated in future studies, and the need for providing early cardiac resynchronization therapy must be emphasized., (© 2022 Wiley Periodicals LLC.)

Objectives: Report contemporary outcomes in patients included in the Mitragister registry and treated with transcatheter mitral valve implantation for failed surgical annuloplasty rings or deteriorated bioprosthesis., Background: Midterm survival rates have been reported, but little is known about contemporary morbimortality endpoints., Methods: The primary safety outcome was the technical success rate. The primary efficacy composite endpoint was a composite of cardiovascular mortality and heart failure hospitalizations., Results: From 2016 to 2021, 102 patients (median age: 81 [74;84] years, 61% female, Euroscore II 11.0% [7.8;16.0]) undergoing valve-in-valve (ViV; n = 89) or valve-in-ring (ViR; n = 13) procedures were consecutively included. At baseline, ViR group patients had worse left ventricular ejection fraction (50% vs. 60%; p = 0.004) and more frequently severe regurgitation (46% vs. 15%; p = 0.014). The primary safety outcome was 95%: 77% and 98% in the ViR and ViV populations, respectively, (p = 0.014). At intermediate follow-up (6-12 months) clinical improvement was notable, 88% of the patients were in NYHA class ≤ II (vs. 25% at baseline; p < 0.001). At a mean follow-up of 17.1 ± 11.0 months, the primary efficacy composite reached 27%. By multivariate analysis, paravalvular leak (PVL) was the only independent predictor (hazard ratio: 2.39, 95% confidence interval: 1.08-5.29; p = 0.031) while ViR was not found statistically associated (p = 0.456)., Conclusions: This study confirms the safety and efficacy of the mitral ViV procedure. ViR patients appear at higher risk of procedural complications. The presence of PVL could be associated with markedly worse midterm prognosis. Whatever the intervention, procedural strategies to reduce PVL incidence remain to be assessed to prevent latter adverse outcomes., (© 2022 Wiley Periodicals LLC.)

Objectives: This study sought to investigate patient intermediate-term outcomes after transcatheter pulmonary valve replacement (TPVR) with Edwards SAPIEN valve., Background: The Edwards SAPIEN valve, initially designed for percutaneous aortic valve replacement, has been approved for TPVR in patients with dysfunctional right ventricular outflow tracts (RVOT), but only short-term follow-up has been reported., Methods: From 2011 to 2016, 62 patients undergoing successful TPVR using the SAPIEN XT valve were consecutively included into the study. Primary efficacy and safety endpoints were defined as freedom from valve-reintervention and freedom from infective endocarditis at last follow-up, respectively., Results: The primary efficacy outcome was met for 87.1% patients after a mean follow-up of 4.6 ± 1.8 years, corresponding to a freedom of reintervention at 5 years of 89% (95% CI 74.8-95.6%). Reinterventions were exclusively due to recurrent obstruction, no significant valvular regurgitation was observed. One case of infective endocarditis was reported, corresponding to a rate of 0.35% per patient-year (95% CI 0.01-2.00%). At 5 years, freedom from infective endocarditis was 98.4% (95% CI 89.1-99.8%). Six patients died or were transplanted due to advanced cardiac failure, without relationship with TPVR. In univariate analysis, reintervention was associated with young age, a smaller tube-graft, a higher pulmonary valve gradient after the procedure and a ratio of largest implanted stent diameter to invasive balloon conduit diameter over 1.35., Conclusions: This study documents the mid-term safety and efficacy of the Edwards SAPIEN XT valve in patients with dysfunctional RVOT, and identifies a patient profile associated with an uncertain benefit-risk balance., (© 2021 Wiley Periodicals LLC.)

Purpose: The COCCINELLE study is a nationwide retrospective French cohort set up to evaluate the risk of cancer in patients who undergone cardiac catheterisation (CC) procedures for diagnosis or treatment of congenital heart disease during childhood., Participants: Children who undergone CC procedures from 1 January 2000 to 31 December 2013, before the age of 16 in one of the 15 paediatric cardiology departments which perform paediatric CC in mainland France were included. The follow-up started at the date of the first recorded CC procedure until the exit date, that is, the date of death, the date of first cancer diagnosis, the date of the 18th birthday or the 31 December 2015, whichever occurred first. The cohort was linked to the National Childhood Cancer Registry to identify patients diagnosed with cancer and with the French National Directory for the Identification of Natural Persons to retrieve the patients' vital status., Findings to Date: A total of 17 104 children were included in the cohort and followed for 110 335 person-years, with 22 227 CC procedures collected. Among the patients, 81.6% received only one procedure. Fifty-nine cancer cases were observed in the cohort. Standardised incidence ratios (SIRs) were increased for all-cancer (SIR=3.8, 95% CI: 2.9 to 4.9), leukaemia (SIR=3.3, 95% CI: 2.0 to 5.4), lymphoma (SIR=14.9, 95% CI: 9.9 to 22.5) and solid cancers excluding central nervous system (CNS) tumours (SIR=3.3, 95% CI: 2.0 to 5.5) compared with the general population., Future Plans: Dose reconstruction is currently underway to estimate individual cumulative doses absorbed to relevant organs, including red bone marrow and brain for respectively haematologic disorders and CNS tumours risk estimation. A dose-response analysis will be conducted with consideration to confounding factors such as age at exposure, gender, predisposing factors to cancer and other sources of medical diagnostic low-dose ionising radiation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The shutdown in economic activity due to the coronavirus disease (COVID-19) crisis has resulted in a short-term decline in global carbon emissions, but the long-term impact of the pandemic on the transition to a low-carbon economy is uncertain. Looking at previous episodes of financial and economic stress to draw implications for the current crisis, we find that tighter financial constraints and adverse economic conditions are generally detrimental to firms' environmental performance, reducing green investments. The COVID-19 crisis could thus potentially slow down the transition to a low-carbon economy. These findings underline the importance of climate policies and green recovery packages to boost green investment and support the energy transition., (© 2021 Elsevier B.V. All rights reserved.)

A 48-year-old who underwent a Mustard operation in 1972 followed by a second cardiac intervention in 1996 for pulmonary venous baffle enlargement and residual baffle leak closure, complicated by recurrent atrial flutter, was admitted to our institution for severe systemic atrio-ventricular valve regurgitation (SAVVR) associated with severely impaired systemic right ventricular (RV) function. After careful preoperative anatomic assessment including three-dimensional transesophageal echocardiography (3DTEE) to define the clipping strategy and computed tomography to optimize the transvenous baffle puncture site, the intervention was performed under general anesthesia, fluoroscopic, and 3DTEE guidance. One XTR MitraClip was successfully implanted, achieving a significant reduction in regurgitation and immediate clinical improvement. The transbaffle puncture was closed using an 8 mm atrial septal defect (ASD) device without residual shunt or obstruction of the venous baffle. Post-operative clinical evaluation showed immediate improvement in the NYHA functional class (from III to II), but the patient presented with recurrent flutter at 1 week after the procedure, which was successfully treated by catheter ablation with another transbaffle approach next to the ASD device. Clinical improvement was maintained at 1- and 6-month follow-up with significant reduction in SAVVR, reduced systemic RV volumes and improved RV ejection fraction. This case demonstrates the feasibility of percutaneous treatment of systemic SAVV in patients with systemic RV after atrial redirection., (© 2021 Wiley Periodicals LLC.)

Aims: Important controversies remain concerning the determinants of life-threatening arrhythmias during ST-segment elevation myocardial infarction (STEMI) and their impact on late adverse events. This study sought to investigate which factors might facilitate ventricular tachycardia (VT) and ventricular fibrillation (VF), in a homogeneous population of anterior STEMI patients defined by abrupt left anterior descending coronary artery (LAD) occlusion and no collateral flow., Methods and Results: The 967 patients, who entered into the CIRCUS (Does Cyclosporine ImpRove Clinical oUtcome in ST elevation myocardial infarction patients) study, were assessed for further analysis. Acute VT/VF was defined as VT (run of tachycardia >30 s either self-terminated or requiring electrical/pharmacological cardioversion) or VF documented by electrocardiogram or cardiac monitoring, during transportation to the cathlab or initial hospitalization. VT/VF was documented in 136 patients (14.1%). Patients with VT/VF were younger and had shorter time from symptom onset to hospital arrival. Site of LAD occlusion, thrombus burden, area at risk, pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction flow, and ST-segment resolution were similar to that of patients without VT/VF. There was no impact of VT/VF on left ventricular remodelling or clinical outcomes. By multivariate analysis, the use of morphine (odds ratio 1.71; 95% confidence interval (1.13-2.60); P = 0.012) was the sole independent predictor of VT/VF occurrence., Conclusions: In STEMI patients with LAD occlusion, our findings support the view that morphine could favour severe ventricular arrhythmias., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

COVID-19 has put each and every one at test. Cardiological clinics are facing constrained resources, limiting timely treatment of patients as usual. Patients with valvular heart disease are one of the most time sensitive patient populations, with delayed therapy possible leading to increased morbidity and mortality. Identifying and allocating the available resources to the most vulnerable patients is crucial in providing optimal patient care with prioritization of essential surgical or percutaneous procedures for valvular heart disease. Implementing telemedicine approaches might help to minimize non-essential physician-to-patient contact to ensure safety, for both patients and lastly but not least the treating physicians., (Published on behalf of the European Society of Cardiology. © The Author(s) 2020.)

Purpose: Interventional cardiology devices and especially stents are constantly evolving. A good radiopacity is essential to properly position the stent and to reduce the risk of complications during percutaneous coronary intervention (PCI). We wanted to assess the radiopacity of coronary stents., Methods: 9 stents were evaluated. Stents were deployed in a silicon bifurcation model and several pulsed fluoroscopy acquisitions (7.5 and 15 pulses/s) of each device were performed in a catheterization laboratory. Quantitative radiopacity assessment was performed using a radiopacity visual scale and qualitative radiopacity assessment was performed by showing the images to three experienced operators, single-blind., Results: Our study showed statistically significant differences between stents regarding radiopacity assessed in a quantitative analysis (p < 0.000001) or a qualitative analysis (p < 0.000001), whether the acquisitions were made in 7.5 or 15 pulses/s. Resolute Onyx and Synergy were the most radio-opaque in both qualitative and qualitative analysis. Moreover, there was a statistically significant correlation between the radiopacity of stents, their strut thickness (p < 0.0001) and the presence of platinum in their metallic alloy (p < 0.0001)., Conclusion: This study highlighted significant differences in the radiopacity of coronary stents deployed in a bench test model. The strut thickness and the presence of platinum increased the radiopacity.

Indoor pollutants can have short- and long-term health effects, especially if exposure occurs during prenatal life or early childhood. This study describe the perceptions, knowledge, and practices of adults concerning indoor environmental pollution. Adults of 18 to 45 years of age were recruited in the department of Ille-et-Vilaine (Brittany-France) in 2019 through a stratified random draw in the waiting rooms of general practitioners (GPs) ( n = 554) who completed a self-questionnaire. The 71% who had already heard of this type of pollution were older ( p = 0.001), predominantly women ( p = 0.007), not expecting a baby ( p = 0.005), and had a higher knowledge score ( p < 0.001). The average knowledge score was 6.6 ± 6.6 out of 11, which was higher for participants living in a couple and with a higher level of education ( p < 0.001). Some practices were well implemented (>80% of participants) (aeration during renovation) whereas others were insufficiently practiced (<60% of participants) (paying attention to the composition of cosmetic products). Factors associated differed depending on the frequency of integration: living in a couple and having a child for well implemented practices and educational level, knowledge level, and perception for those under implemented. Knowledge must be improved to modify perceptions and certain practices, making sure not to increase social inequalities in health., Competing Interests: The authors declare no conflicts of interest.

On 27 December 2019, the French Public Health Agency identified a large increase in the number of acute gastroenteritis and vomiting visits, both in emergency departments and in emergency general practitioners' associations providing house-calls. In parallel, on 26 and 27 December, an unusual number of food-borne events suspected to be linked to the consumption of raw shellfish were reported through the mandatory reporting surveillance system. This paper describes these concomitant outbreaks and the investigations' results.

Background: Unlike previous randomized clinical trials (RCTs), recent trials and meta-analyses have shown that transcatheter closure of patent foramen ovale (PFO) reduces stroke recurrence risk in young and middle-aged adults with an otherwise unexplained PFO-associated ischaemic stroke., Aim: To produce an expert consensus on the role of transcatheter PFO closure and antithrombotic drugs for secondary stroke prevention in patients with PFO-associated ischaemic stroke., Methods: Five neurologists and five cardiologists with extensive experience in the relevant field were nominated by the French Neurovascular Society and the French Society of Cardiology to make recommendations based on evidence from RCTs and meta-analyses., Results: The experts recommend that any decision concerning treatment of patients with PFO-associated ischaemic stroke should be taken after neurological and cardiological evaluation, bringing together the necessary neurovascular, echocardiography and interventional cardiology expertise. Transcatheter PFO closure is recommended in patients fulfilling all the following criteria: age 16-60 years; recent (≤6 months) ischaemic stroke; PFO associated with atrial septal aneurysm (>10mm) or with a right-to-left shunt>20 microbubbles or with a diameter≥2mm; PFO felt to be the most likely cause of stroke after thorough aetiological evaluation by a stroke specialist. Long-term oral anticoagulation may be considered in the event of contraindication to or patient refusal of PFO closure, in the absence of a high bleeding risk. After PFO closure, dual anti-platelet therapy with aspirin (75mg/day) and clopidogrel (75mg/day) is recommended for 3 months, followed by monotherapy with aspirin or clopidogrel for≥5 years., Conclusions: Although a big step forward that will benefit many patients has been taken with recent trials, many questions remain unanswered. Pending results from further studies, decision-making regarding management of patients with PFO-associated ischaemic stroke should be based on a close coordination between neurologists/stroke specialists and cardiologists., (Copyright © 2019.)

Aims: The proximal optimization technique (POT) in coronary bifurcation stenting improves apposition and side-branch obstruction. The POT balloon should be positioned with the distal radio-opaque marker at the carina cut plane. However, the real impact of positioning remains unknown., Methods and Results: Synergy™ stents (Boston Scientific, USA) were implanted on left-main fractal bench models. Initial POT was performed in 3 positions according to distal shoulder position (loss of balloon parallelism) relative to the carina cut plane (n = 5/group): i) "proximal", 1 mm before carina; ii) "medium", just at carina; iii) "distal", 1 mm after carina. Results were quantified on 2D- and 3D-OCT. Compared to implantation, initial POT improved malapposition in all positions ("proximal": 61.5 ± 1.4% vs. 5.1 ± 2.7%; "medium": 60.2 ± 2.4% vs. 1.3 ± 0.6%; "distal": 60.5 ± 2.9% vs. 1.1 ± 1.8%, p < 0.05). However, residual malapposition was greater in "proximal" position (p < 0.05). "Proximal", unlike "medium" or "distal" POT, also failed to improve side-branch obstruction. Conversely, "distal" POT significantly overstretched the main-branch ostium, with stent/artery ratio 1.22 ± 0.04 vs. 1.11 ± 0.07 for "medium" POT (p < 0.05)., Conclusion: Shoulder positioning is essential to optimize the mechanical benefit of POT without main-branch overstretch (too distal position). Experimentally, the best position is just at the carina cut plane ("medium")., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Unlike previous randomized clinical trials (RCTs), recent trials and meta-analyses have shown that transcatheter closure of patent foramen ovale (PFO) reduces stroke recurrence risk in young and middle-aged adults with an otherwise unexplained PFO-associated ischaemic stroke., Aim: To produce an expert consensus on the role of transcatheter PFO closure and antithrombotic drugs for secondary stroke prevention in patients with PFO-associated ischaemic stroke., Methods: Five neurologists and five cardiologists with extensive experience in the relevant field were nominated by the French Neurovascular Society and the French Society of Cardiology to make recommendations based on evidence from RCTs and meta-analyses., Results: The experts recommend that any decision concerning treatment of patients with PFO-associated ischaemic stroke should be taken after neurological and cardiological evaluation, bringing together the necessary neurovascular, echocardiography and interventional cardiology expertise. Transcatheter PFO closure is recommended in patients fulfilling all the following criteria: age 16-60 years; recent (≤6 months) ischaemic stroke; PFO associated with atrial septal aneurysm (>10mm) or with a right-to-left shunt>20 microbubbles or with a diameter≥2mm; PFO felt to be the most likely cause of stroke after thorough aetiological evaluation by a stroke specialist. Long-term oral anticoagulation may be considered in the event of contraindication to or patient refusal of PFO closure, in the absence of a high bleeding risk. After PFO closure, dual anti-platelet therapy with aspirin (75mg/day) and clopidogrel (75mg/day) is recommended for 3 months, followed by monotherapy with aspirin or clopidogrel for≥5 years., Conclusions: Although a big step forward that will benefit many patients has been taken with recent trials, many questions remain unanswered. Pending results from further studies, decision-making regarding management of patients with PFO-associated ischaemic stroke should be based on a close coordination between neurologists/stroke specialists and cardiologists., (Copyright © 2019. Published by Elsevier Masson SAS.)

Aims: Percutaneous mitral valve repair has become an alternative to conventional surgery in patients suffering primary mitral regurgitation (MR) with a contraindication to surgery and could benefit patients at high surgical risk. The aim of the MITRA-HR study is to raise the level of evidence supporting the use of the MitraClip device in primary MR patients with a predefined high risk for surgery., Methods and Results: MITRA-HR is a prospective, multicentre, randomised study designed to compare mitral valve repair using the MitraClip with conventional surgery in patients with severe primary mitral regurgitation at high risk for surgery. The surgical risk is defined by age, Society of Thoracic Surgeons (STS) risk estimate score, frailty, major organ system dysfunction, and procedure-specific impediments. The study will enrol 330 patients randomised between conventional surgery and MitraClip with a 1:1 ratio. The composite primary endpoint includes all-cause mortality, unplanned rehospitalisation for cardiovascular reasons, and mitral valve reintervention at 12 months. The main secondary safety endpoint is a major adverse event composite assessment evaluated 30 days after the procedure., Conclusions: The randomised MITRA-HR study is designed to provide additional supportive evidence of non-inferiority in efficacy and superiority in safety for percutaneous mitral valve repair using the MitraClip compared to conventional surgery in high surgical risk patients.

Mitral regurgitation (MR) is the second most common form of valvular heart disease. It is classified as either primary (degenerative) or secondary (functional). Secondary MR is the consequence of myocardium disease. Primary MR from degenerative valve disease is due to a primary disruption of the mitral valve apparatus from either prolapsed or flail leaflets. It covers all aetiologies in which intrinsic lesions affect one or several components of the mitral valve apparatus. Gold-standard therapeutic management of severe primary MR is surgery usually to repair but sometime to replace the mitral valve. However patients considered to be at high-risk due to their age or the presence of comorbidities - accounting for 50% of all patients - are not eligible for surgery. Catheter-based interventions have been developed to correct MR percutaneously. The only such intervention which has been evaluated in organic MR is the edge-to-edge procedure using the MitraClip ® (Abbott Vascular, Menlo Park, CA). MitraClip ® offers an alternative to open surgical repair or replacement via a minimally invasive route and it was shown in the EVEREST II study that MitraClip ® was safer than surgery even though it was less effective in reducing MR. A substantial number of patients are ineligible for mitral valve surgery because of prohibitive surgical risk. For those patients, MitraClip ® may offer an alternative treatment option. Percutaneous edge-to-edge repair is the first percutaneous option accepted in the 2012 ESC guidelines: Percutaneous edge-to-edge procedure may be considered in patients with symptomatic severe primary MR who fulfill the echo criteria of eligibility, are judged inoperable or at high surgical risk by a 'heart team', and have a life expectancy greater than 1 year (recommendation class IIb, level of evidence C). Because of its frailty, MitraClip ® in the elderly may be a good alternative to mitral surgery when indicated for primary or secondary MD., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to describe and analyze data from patients treated in France with the Edwards SAPIEN transcatheter heart valve (Edwards Lifesciences LLC, Irvine, California) in the pulmonary position., Background: The Edwards SAPIEN valve has recently been introduced for percutaneous pulmonary valve implantation (PPVI)., Methods: From April 2011 to May 2017, 71 patients undergoing PPVI were consecutively included., Results: The median age at PPVI was 26.8 years (range 12.8 to 70.1 years). Primary underlying diagnoses were conotruncal malformations (common arterial trunk, tetralogy of Fallot and variants; n = 45), Ross procedure (n = 18), and other diagnoses (n = 8). PPVI indication was pure stenosis in 33.8% of patients, pure regurgitation in 28.1%, and mixed lesions in 38.1%. PPVI was successfully implemented in 68 patients (95.8%). Pre-stenting of the right ventricular outflow tract was performed in 70 patients (98.6%). Early major complications occurred in 4 subjects (5.6%), including 1 death, 1 coronary compression, and 2 pulmonary valve embolizations. Three of the 4 major complications occurred in the first 15 operated patients. No significant regurgitation was recorded after the procedure. Transpulmonary gradient was significantly reduced from 34.5 to 10.5 mm Hg (p < 0.0001). No patient died during a 1-month follow-up period. At 1-year follow-up, the death rate was 2.9%, and 3 patients had undergone surgical reintervention (44%)., Conclusions: Early results with the Edwards SAPIEN valve in the pulmonary position demonstrate an ongoing high rate of procedural success., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous pulmonary valve implantation (PPVI) is a routine treatment for dysfunctional right ventricular outflow tract. Infective endocarditis (IE) is a major concern., Aim: To report French experience with the Melody™ valve (Medtronic Inc., Minneapolis, MN, USA)., Methods: All patients who underwent PPVI were recorded in a multicentre French national survey. Demographic and procedural data were collected from patients with IE. Bacterial identification, diagnostic tools and outcome were recorded., Results: Forty-five cases of IE were diagnosed in 43 patients. The cumulative IE incidence was 11.8% (95% confidence interval [CI] 8.5-15.9). The annualized IE incidence was 3.6% (95% CI 0-4.8). Freedom from IE was 96.3% and 85.8% at 12 months and 60 months, respectively. IE incidence did not change during the study period. The mean interval between PPVI and IE was 2.6±2.1 years (range, 5 days to 7.3 years). Fifteen patients with IE required intravenous antibiotics only. Seven patients had early interventional cardiac catheterization to relieve severe right ventricular outflow tract obstruction. Twenty-four patients had surgical valve replacement (six urgently; nine semi-urgently; nine electively). Staphylococcus aureus IE required surgery in all but one patient. Three patients died before any treatment. Three additional patients died, giving a mortality rate of 14%. Global survival in the total cohort of patients who received a Melody valve was excellent (96.5% at 5 years). When comparing survival curves between the IE and non-IE groups, death and cardiovascular events were statistically significantly higher in the IE group (log-rank P<0.0001)., Conclusion: Melody valve IE is a severe complication following PPVI. The annualized IE incidence in this cohort was similar to rates reported in other studies. With rapid diagnosis and adequate treatment, outcome has improved, and unfavourable outcome is mainly associated with S. aureus., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with PFO-associated cryptogenic stroke., Methods and Results: We searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (RRs) were calculated in random-effects meta-analyses. PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6 RCTs; RR=0.36, 95% CI: 0.17-0.79; I 2 =59%). The effect of PFO closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (RR=0.27, 95% CI, 0.11-0.70; I 2 =42%) compared with patients without these anatomical features (RR=0.80, 95% CI, 0.43-1.47; I 2 =12%). Major complications occurred in 2.40% (95% CI, 1.03-4.25; I 2 =77%) of procedures. New-onset atrial fibrillation was more frequent in patients randomized to PFO closure versus antithrombotic therapy (RR=4.33, 95% CI, 2.37-7.89; I 2 =14%). One RCT compared PFO closure versus anticoagulation (353 patients; hazard ratio=0.14, 95% CI, 0.00-1.45) and 2 RCTs compared PFO closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95% CI, 0.05-0.63; I 2 =12%). Three RCTs compared anticoagulation versus antiplatelet therapy, with none showing a significant difference., Conclusions: PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle-aged patients. PFO closure was associated with an increased risk of atrial fibrillation., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

The development of structural interventional catheterization for acquired or congenital heart disease was made possible through concomitant advances in catheterization techniques/tools and imaging techniques (fluoroscopy, ultrasound, magnetic resonance imaging and computed tomography). Imaging should provide an accurate view of the lesions and the surrounding cardiac structures, as well as the medical devices and catheters used. Here, we address the subject of image fusion. The principle of image fusion is based on the superposition of several imaging techniques: real-time fluoroscopy and multislice imaging performed offline or ultrasound imaging performed simultaneously. The goals are to improve the overall visualization of the organ and the surrounding structures, and to help the interventional cardiologist to interpret fluoroscopy images., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Several publications have considered results of percutaneous angioplasty for aortic recoarctation, but none focused on procedures performed in children aged<1 year., Aims: To describe the immediate and midterm results of balloon angioplasty for recoarctation before the age of 1 year, and to define the factors that might influence outcome., Methods: We retrospectively reviewed data from 20 consecutive children undergoing percutaneous dilatation for aortic recoarctation before the age of 1 year in the University Hospitals of Tours and Nantes., Results: In all patients except one, dilatation improved the median recoarctation diameter Z-score from -5.5 (range -10.6 to -2.5) to -2.8 (range -4.3 to 0.7) (P<0.001), and reduced the median peak systolic gradient from 33mmHg (range 20 to 60mmHg) to 21mmHg (range 6 to 50mmHg) (P<0.001). There was no procedure-induced mortality and no acute intimal flap or long-term aneurysm. Three patients experienced a transient femoral artery thrombosis, one of whom had a transient ischemic stroke. Eight children (40%) needed reintervention for further recoarctation (new surgery [n=4] or new dilatation [n=4]). A smaller balloon size was significantly associated with the risk of reintervention: balloon to recoarctation diameter ratio 2.0 (range 1.3 to 3.3) vs. 2.7 (range 2.1 to 4.5) (P=0.05); balloon to descending aorta ratio 0.8 (range 0.7 to 1.2) vs. 1.0 (range 0.9 to 1.3) (P<0.05)., Conclusions: In this study, percutaneous balloon angioplasty for recoarctation in young infants aged<1 year improved aortic isthmus diameter with a low incidence of adverse event. However, the rate of further intervention is high, and is associated with a smaller balloon size., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations have been shown to be positively associated with LDL cholesterol (LDL-C), but the relationship between PCSK9 and coronary atherosclerosis lesions remains unclear., Objective: This study aims to investigate the correlation between serum PCSK9 levels and coronary damage severity in patients hospitalized for acute coronary syndrome (ACS)., Methods: In this prospective proof-of-concept study, coronary lesions were assessed using SYNTAX scores. Serum PCSK9 concentrations were measured on admission (Day 0) for ACS by Elisa, and on every day of hospitalization. Spearman's correlations were used to determine the association between PCSK9 levels, SYNTAX score and metabolic parameters., Results: A total of 174 patients (mean age: 59±14 years, 79% male) with ACS (on Day 0, 119 patients were not taking statins, but 55 were) were included. After initiation of high-intensity statin therapy, serum PCSK9 concentrations increased significantly, reaching maximum levels on Day 2 (+31% vs. Day 0), and remained stable up to Day 4 (P<0.001, by mixed model). Serum PCSK9 on Day 0 was associated with LDL-C (rho=0.226, P=0.017) and apolipoprotein B (rho=0.282, P=0.005) in the statin-naïve group only, and with triglycerides and non-HDL-C in all groups. More important, PCSK9 levels on Day 0 were positively associated with SYNTAX scores in the statin-naïve group (rho=0.239, P=0.009), but not in the statin-treated group (P=NS). This association was maintained after adjusting for LDL-C (P=0.014) and major CV risk factors (P=0.008)., Conclusion: Serum PCSK9 levels are positively associated with severity of coronary artery lesions independently of LDL-C concentrations in patients hospitalized for ACS. This reinforces the potential importance of PCSK9 inhibition in the management of ACS., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy., Methods: In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3., Results: A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone., Conclusions: Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289 .).

The extreme radiation resistance of Deinococcus bacteria requires the radiation-stimulated cleavage of protein DdrO by a specific metalloprotease called IrrE. DdrO is the repressor of a predicted radiation/desiccation response (RDR) regulon, composed of radiation-induced genes having a conserved DNA motif (RDRM) in their promoter regions. Here, we showed that addition of zinc ions to purified apo-IrrE, and short exposure of Deinococcus cells to zinc ions, resulted in cleavage of DdrO in vitro and in vivo, respectively. Binding of IrrE to RDRM-containing DNA or interaction of IrrE with DNA-bound DdrO was not observed. The data are in line with IrrE being a zinc peptidase, and indicate that increased zinc availability, caused by oxidative stress, triggers the in vivo cleavage of DdrO unbound to DNA. Transcriptomics and proteomics of Deinococcus deserti confirmed the IrrE-dependent regulation of predicted RDR regulon genes and also revealed additional members of this regulon. Comparative analysis showed that the RDR regulon is largely well conserved in Deinococcus species, but also showed diversity in the regulon composition. Notably, several RDR genes with an important role in radiation resistance in Deinococcus radiodurans, for example pprA, are not conserved in some other radiation-resistant Deinococcus species., (© 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Objective: Some patients suffering from pelvi-perineal chronic pain express urgent, even vital, demands of care. The objective was to compare the profile and the psychological functioning of the patients, who have shown an imperious demand of care, in that of the patients who do not have an imperious demand of care., Material and Method: From the medical consultations for chronic pelviperineal pain, we realized a comparative study including 26 patients (experimental group) expressing an urgent demand of care (i.e., patients who, during the last 3months, called an emergency service concerning the pains for which they consult in the service) and 28 patients (control group) without an urgent demand of care (i.e., patient who, during the last 3months, did not call an emergency service concerning the pains for which they consult in the service). All the patients were tested through a cognitive task of decision-making (Iowa Gambling Task) and through explicit measures of pain and its main psychological associated factors (anxiety, depression, impulsivity an catastrophism)., Results: In the first place, the patients from the experimental group possess decision-making abilities equivalent to the patients of the control group; however, both groups of patients show, in the beginning of the test, a deficit in the decision-making (F(4.208)=3.4116; P=.009). Secondly, the measures to questionnaires reveal that the patients of the control group have less severe scores in the scales of depression (t(52)=-2.068; P<04), catastrophism (amplification : t(52)=-3.069; P<0035; powerlessness: t(52)=-2.866, P<.006) and impulsivity (positive urgency: t(52)=-2.246, P<029; lack of premeditation: t(52)=-2.175, P<035) than the patients of the experimental group., Conclusion: The use of explicit measures (questionnaire) and implicit measures (experimental task) allowed to objectify more precisely the differences between the chronic pain patients in urgent demand of care and the other chronic pain patients. This psychological specificity obliges us to approach differently the caring of these patients in particular by proposing adapted cognitivo-behavioral techniques., Level of Evidence: 3., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Giving paper and polymer photochromic properties under laser irradiation is challenging due to the low resistance of these materials to heat, their flexibility, and their possibly irregular structure. However, we could successfully deposit TiO 2 /Ag/TiO 2 layers stacking on flexible white glossy paper and transparent polyethylene terephalate (PET) substrates using a reactive magnetron sputtering technique, and tailor coloration changes after laser irradiation, alternating visible and ultraviolet (UV) wavelengths. The sample colors are characterized by a panel of chromas depending on the irradiation conditions. We demonstrate that these chroma changes are due to morphological changes of Ag nanoparticles (NPs) after visible laser irradiation of the colored as-deposited sample. The process exhibits a good reversibility after subsequent UV irradiation due to the growth of new metallic Ag NPs. The colors displayed in diffuse reflection by the paper samples are more saturated than the ones displayed in regular transmission by PET samples. We demonstrate the efficiency of the photochromic process on such support by printing high resolution patterns exhibiting different colors depending on the observation conditions.

Cardiac catheterization has greatly contributed to the progress made in the management of congenital heart diseases (CHD). Initially used in diagnosis, it allowed the understanding of heart diseases, their anatomy and hemodynamics. Gradually, the development of interventional cardiology has played a major role in the management of these malformations (Patent ductus arteriosus [PDA] and atrial septal defect [ASD] closure, pulmonary dilatation, percutaneous pulmonary valve implantation…). The development of such technology was made possible through the concomitant development of imaging techniques: fluoroscopy, ultrasound, MRI and CT. Imaging should provide an accurate view of the lesions, the surrounding cardiac structures, as well as medical devices and catheters used. Here we address the field of fusion images. The principle of image fusion is based on the association by superposition of several imaging techniques: real-time fluoroscopy and slice imaging performed offline, or ultrasound imaging performed simultaneously. The goal is to improve the overall view of the organ, its surrounding structures and as the consequence to help the interventional cardiologist., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: The aim of this study was to describe a tool based on vaccine sales to estimate vaccination coverage against seasonal influenza in near real-time in the French population aged 65 and over., Methods: Vaccine sales data available on sale-day +1 came from a stratified sample of 3004 pharmacies in metropolitan France. Vaccination coverage rates were estimated between 2009 and 2014 and compared with those obtained based on vaccination refund data from the general health insurance scheme., Results: The seasonal vaccination coverage estimates were highly correlated with those obtained from refund data. They were also slightly higher, which can be explained by the inclusion of non-reimbursed vaccines and the consideration of all individuals aged 65 and over. We have developed an online tool that provides estimates of daily vaccination coverage during each vaccination campaign., Conclusion: The developed tool provides a reliable and near real-time estimation of vaccination coverage among people aged 65 and over. It can be used to evaluate and adjust public health messages., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Rationale: Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale, oral anticoagulants and antiplatelet therapy in patients with patent foramen ovale-associated cryptogenic stroke, Aim: To assess whether transcatheter patent foramen ovale closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy, for secondary stroke prevention in patients aged 16 to 60 years with a large patent foramen ovale or a patent foramen ovale associated with an atrial septal aneurysm, and an otherwise unexplained ischaemic stroke or retinal ischaemia., Sample Size: Six hundred and sixty-four patients were included in the study., Methods and Design: CLOSE is an academic-driven, multicentre, randomized, open-label, three-group, superiority trial with blinded adjudication of outcome events. The trial has been registered with Clinical Trials Register (Clinicaltrials.gov, NCT00562289). Patient recruitment started in December 2007. Patient follow-up will continue until December 2016. Expected mean follow-up = 5.6 years., Study Outcomes: The primary efficacy outcome is the occurrence of fatal or nonfatal stroke. Safety outcomes include fatal, life-threatening or major procedure- or device-related complications and fatal, life-threatening or major haemorrhagic complications., Discussion: CLOSE is the first specifically designed trial to assess the superiority of patent foramen ovale closure over antiplatelet therapy alone and the superiority of oral anticoagulants over antiplatelet therapy to prevent stroke recurrence in patients with patent foramen ovale-associated cryptogenic stroke., (© 2016 World Stroke Organization.)

Objectives: The short-term efficacy and safety of transcatheter closure (TCC) for the management of coronary artery fistulas (CAFs) was investigated in pediatric patients., Background: CAFS are rare with potentially severe complications and their management is still a matter of debate. Percutaneous closure appears to be the treatment of choice in anatomically suitable vessels but limited data are available in the pediatric population., Methods: This retrospective, observational, multicenter, national study included patients under 16 years of age who underwent TCC of a congenital CAF. Patients with additional congenital heart defect were excluded., Results: 61 patients (36 girls, 25 boys) with a median age of 0.6 year [0-15.4] at diagnosis and 3.9 years [0-16] at procedure were included. The CAF was large in 48 patients (79%); it was distal in 23 (38%) and proximal in 22 (36%). Most patients (77%) were asymptomatic at diagnosis. Clinical signs of congestive heart failure were present in seven patients (11%). Perioperative complications included three cases of ST elevation myocardial infarction (exclusively during attempted closure of a distal CAF), three devices migrations, and one case of leg ischemia. One patient died after surgical closure of a large distal CAF that could not be closed by TCC. Follow-up data were collected for 43 patients (70%) for a median of 91 days [0-4,824]. The Kaplan-Meyer estimate for complete occlusion at 2 years was 73 ± 7.6%., Conclusion: TCC in the pediatric population appears to be effective and associated with few complications., (© 2015 Wiley Periodicals, Inc.)

This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (<8 %) were found in just two of the countries, whilst substandard artemisinin-based combinations were present in all six countries and, artemisinin-based monotherapy tablets are still available in some places despite the fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting.

Cardiac catheterization has contributed to the progress made in the management of patients with congenital heart disease (CHD). First, it allowed clarification of the diagnostic assessment of CHD, by offering a better understanding of normal cardiac physiology and the pathophysiology and anatomy of complex malformations. Then, it became an alternative to surgery and a major component of the therapeutic approach for some CHD lesions. Nowadays, techniques have evolved and cardiac catheterization is widely used to percutaneously close intracardiac shunts, to relieve obstructive valvar or vessel lesions, and for transcatheter valve replacement. Accurate imaging is mandatory to guide these procedures. Cardiac imaging during catheterization of CHD must provide accurate images of lesions, surrounding cardiac structures, medical devices and tools used to deliver them. Cardiac imaging has to be 'real-time' with an excellent temporal resolution to ensure 'eyes-hands' synchronization and 'device-target area' accurate positioning. In this comprehensive review, we provide an overview of conventional cardiac imaging tools used in the catheterization laboratory in daily practice, as well as the effect of recent evolution and future imaging modalities., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

PprA, a radiation-induced Deinococcus-specific protein, was previously shown to be required for cell survival and accurate chromosome segregation after exposure to ionizing radiation. Here, we used an in vivo approach to determine, by shotgun proteomics, putative PprA partners coimmunoprecipitating with PprA when cells were exposed to gamma rays. Among them, we found the two subunits of DNA gyrase and, thus, chose to focus our work on characterizing the activities of the deinococcal DNA gyrase in the presence or absence of PprA. Loss of PprA rendered cells hypersensitive to novobiocin, an inhibitor of the B subunit of DNA gyrase. We showed that treatment of bacteria with novobiocin resulted in induction of the radiation desiccation response (RDR) regulon and in defects in chromosome segregation that were aggravated by the absence of PprA. In vitro, the deinococcal DNA gyrase, like other bacterial DNA gyrases, possesses DNA negative supercoiling and decatenation activities. These two activities are inhibited in vitro by novobiocin and nalidixic acid, whereas PprA specifically stimulates the decatenation activity of DNA gyrase. Together, these results suggest that PprA plays a major role in chromosome decatenation via its interaction with the deinococcal DNA gyrase when D. radiodurans cells are recovering from exposure to ionizing radiation. IMPORTANCE D. radiodurans is one of the most radiation-resistant organisms known. This bacterium is able to cope with high levels of DNA lesions generated by exposure to extreme doses of ionizing radiation and to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Here, we identified partners of PprA, a radiation-induced Deinococcus-specific protein, previously shown to be required for radioresistance. Our study leads to three main findings: (i) PprA interacts with DNA gyrase after irradiation, (ii) treatment of cells with novobiocin results in defects in chromosome segregation that are aggravated by the absence of PprA, and (iii) PprA stimulates the decatenation activity of DNA gyrase. Our results extend the knowledge of how D. radiodurans cells survive exposure to extreme doses of gamma irradiation and point out the link between DNA repair, chromosome segregation, and DNA gyrase activities in the radioresistant D. radiodurans bacterium.

Background: Many stents are used "off-label" during the management of congenital heart diseases (CHD)., Aims: To describe indications for, results of, and adverse events associated with stenting in CHD in current practice., Methods: Participation in this study was proposed to all catheterization laboratories that specialize in CHD in France (M3C network). All paediatric and adult CHD cases with stent implantation in 2013 were included retrospectively., Results: Overall, 207 stents were implanted in 151 patients across 11 centres. Median age was 13.7 years (range, 5 days to 70.1 years). Main procedure indications were branch pulmonary artery angioplasty (n=46, 29.1%), aortic (re)coarctation stenting (n=43, 27.2%), percutaneous pulmonary valve implantation (n=32, 20.2%) and ductus arteriosus stenting (n=14, 8.9%). The main stents implanted were the CP Stent™ (n=61, 29.5%), the Max™ LD stent (n=43, 20.8%), the Valeo(®) stent (n=28, 13.5%) and valved stents (n=30, 14.5%). Procedures were considered successful in 96.8% of cases (95% confidence interval [CI] 92.8-99.0%). Adverse events were observed in 23 procedures (14.7%, 95% CI 9.5-21.0%). Ductus arteriosus stenting (odds ratio 12.4, 95% CI 2.0-77.5; P<0.01) and pulmonary revalvulation (odds ratio 5.9, 95% CI 1.1-32.3; P=0.04) were risk markers for stent-related adverse events., Conclusions: Stents are used in various CHD catheterization procedures, from infancy to adult age. The adverse events rate is significant and is related to the type of procedure., (Copyright © 2015. Published by Elsevier Masson SAS.)

Background: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling., Methods: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume., Results: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups., Conclusions: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).