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The aim of this multicenter study was to characterize the efficacy and safety of subcutaneous implantable cardioverter-defibrillators (S-ICDs) lead extraction procedures.S-ICDs have been developed to limit lead-related complications inherent to transvenous ICD devices. To date, no study has specifically investigated the safety and feasibility of S-ICD lead extraction procedures.Patients requiring S-ICD lead extraction between February 1, 2014, and February 28, 2019, were retrospectively included in 10 centers. The primary endpoint of the study was procedural success, defined as the removal of all the lead and lead material from the subcutaneous space. Secondary endpoints included procedural complications and the need for specific extraction tools.S-ICD lead extraction procedures were performed in 32 patients (mean age 45.7 ± 13.8 years, 75.0% men, 65.6% in primary prevention). The median time from S-ICD lead implantation was 9.3 months (5.4 to 17.5 months). The primary endpoint, that is, complete removal of the material, was achieved in 96.9% of the patients, and only 1 procedural failure occurred (3.1%). Simple traction of the S-ICD lead was successful in 19 patients (59.4%), whereas 3 patients (9.4%) needed an additional incision and 9 patients (28.1%) required mechanical sheath to remove lead adhesions around the coil. No procedure-related complications occurred. Patients with successful simple traction extraction were implanted more recently (7.1 months [2.8 to 12.2 months] vs. 16.5 months [7.5 to 20.8 months]; p = 0.04) and had less prior history of sternotomy (2 [10.5%] vs. 5 [38.5%] patients; p = 0.09).S-ICD lead extraction is an efficient and safe procedure, but may require some specific tools like mechanical sheath, specifically when fibrotic adhesions developed around the parasternal coil.

Background Brugada syndrome (BrS) is an inherited arrhythmia syndrome with an increased risk of SCD. While Subcutaneous ICD (S-ICD) is a seductive approach to treat these patients, questions raised on the risk of inappropriate shock in this specific population. Objective The aim of this study was to evaluate the safety and the effectiveness of the S-ICD in BrS patients. Methods We prospectively enrolled 112 BrS patients implanted with S-ICD in 17 European centers. During the screening at least 2 vectors must be suitable but it was not necessary to check for the suitability of the ECG during sodium channel blocker or exercise test. S-ICD indications follow the current guidelines. Results Mean age of patients was 45±13 years, with 95 (85%) males. Implantation was performed in 91 (83%) patients for primary prevention and in 18 (16%) patients for secondary prevention. There is an indication of ICD replacement for 16 patients (14%): 13 lead defect (81%), 1 infection (6%) and 2 ICD end of life (13%). In this cohort, 57 patients (51%) had spontaneous type I BrS, 60 patients (55%) were symptomatic: 10 resuscitated SCD (17%) and 48 (83%) syncope. Implantation was performed under general anesthesia in 79 patients (71%). The mean operation time was 56±19 min. The lead was placed at the left side of the sternum in 102 patients (92%) and at the right side in 9 (8%). Sensing configuration was the primary vector for 46 patients (41%), secondary vector for 57 (51%) and alternative vector for 9 (8%). No complications occurred during implantation. During a mean follow-up of 15.6 months (0–39 months), 6 patients (5%) had at least one appropriate shock (n=9). The rate of appropriate shock was 4.5%/y. All the VF episodes were successfully treated with the first shock. One patient had VF ablation for recurrent VF. Among the 6 patients who received an appropriate shock, 3 (50%) were implanted for secondary prevention and 3 (50%) were implanted for primary prevention including 2 patients with a history of syncope and one asymptomatic patient. Twelve patients (11%) had at least one inappropriate shock (n=22) including 2 patients with respectively 8 and 4 inappropriate shocks due to T-wave oversensing. With the SMART pass system the first patient had no more inappropriate shock for now 2 years. The rate of inappropriate shock was 9%/y. One patient died of myocardial infarction. Five patients (4%) were hospitalized for complications (4 pocket or scar infections and 1 electrode failure). Conclusion Our initial experience showed that S-ICD is efficient to treat VF episode in BrS patients. In this population, the rate of inappropriate shock was 9%/y. In view of these results, S-ICD implantation seems to be efficient to protect BrS patients against SCD. Acknowledgement/Funding Investigator-Sponsored Research program, Boston Scientific

Background Ventricular arrhythmias and sudden death are potential late complications in patients with tetralogy of Fallot. Data regarding the value of implantable cardioverter defibrillators (ICD) are scarce in this population. Purpose To assess long-term rates of appropriate ICD therapies and ICD-related complications in a large registry of ICD recipients with tetralogy of Fallot. Methods The DAI-T4F study is an ongoing national French registry including all patients with tetralogy of Fallot and ICD (NCT03837574). Information have been collected prospectively since 2010 with annual update. Baseline patient characteristics and clinical events during follow-up were analyzed with central adjudication. Cox proportional hazard models were used to identify factors associated with appropriate ICD therapies and complications. Results A total of 134 patients (median age 41.7 years, 70.7% males) were enrolled. The median (IQR) follow-up duration was 6.1 (2.7–10.2) years. ICDs were implanted for primary prevention in 47 (35.1%) patients and for secondary prevention in 87 (64.9%) patients. Overall, 14 (29.8%) and 45 (51.7%) patients received at least one appropriate ICD therapy in primary and secondary prevention, respectively, giving annual incidences of 5.5% and 7.1% (p=0.06). Patients with altered left ventricle ejection fraction (LVEF) at inclusion ≤35% experienced less appropriate ICD therapies (HR=0.31, 95% CI: 0.11–0.86, p=0.02), whereas a history of sustained or non-sustained ventricular arrhythmia (HR=2.7, 95% CI: 1.2–3.9, p=0.03) was positively associated with appropriate therapies. Fifty-seven (42.5%) patients had ICD-related complications, including 32 (24.2%) inappropriate ICD shocks, 22 (16.4%) significant lead dysfunction, 14 (10.4%) device infection, and 5 (3.7%) generator dysfunction/recall. History of supraventricular arrhythmias (HR=2.2, 95% CI: 1.2–3.7, p=0.01) and congestive heart failure (HR=2.0, 95% CI: 1.2–3.6, p=0.01) were both associated with a higher risk of complications. During follow-up, 7 (5.2%) patients underwent cardiac transplantation and 12 (9.0%) patients died, mainly from progressive heart failure (n=5). Only one sudden death due to electrical storm was recorded. Figure 1 Conclusions Appropriate therapies are frequent in patients with tetralogy of Fallot and ICDs, including in primary prevention. The relatively important proportion of ICD-related complication highlights the need for improving risk stratification in this population, considering associated conditions in the individual benefit-risk equation.

Background Ventricular arrhythmias and sudden death are feared late complications in patients with tetralogy of Fallot. Selection of candidates for primary prevention implantable cardioverter defibrillator (ICD) remains challenging in this population. Non-sustained ventricular tachycardia (NSVT), altered left ventricular ejection fraction (LVEF), positive programmed ventricular stimulation, and enlarged QRS are currently used for risk stratification. Purpose To identify high-risk patients with tetralogy of Fallot in the setting of primary prevention of sudden cardiac death. Methods The DAI-T4F study is a large ongoing national French registry including all patients with tetralogy of Fallot and ICD (NCT03837574). Information have been collected prospectively since 2010 with annual update. Baseline patient characteristics and clinical events during the follow-up were analyzed with central adjudication. Cox proportional hazard models were used to identify factors associated with appropriate ICD therapies. Results Among 134 patients enrolled, 47 (35.1%) underwent ICD implantation for primary prevention (median age 49.1 years, 76.6% males). At baseline, 20 (42.6%) patients had NSVT, 17 (36.2%) had severe altered LVEF ≤35%, 16 (34.0%) had positive programmed ventricular stimulation, and 16 (34.0%) had QRS duration ≥180ms. Overall, 20 (42.6%), 15 (31.9%), and 6 (12.8%) patients had respectively one, two, or ≥ three of these risk factors. Six (12.8%) patients were implanted for other indications. During a median (IQR) follow-up duration of 5.3 (2.1–8.0) years, 14 (29.8%) patients had at least one appropriate ICD therapy. The annual incidence of appropriate ICD therapies were 2.8%, 4.6%, 6.3%, and 8.6% in patients with none, one, two, or ≥ three of these factors (p for trend = 0.145). None of predictors, considered isolated, was significantly associated with ICD appropriate therapies. Patients with non-sustained ventricular tachycardia (NSVT) and positive programmed ventricular stimulation had a significant increased risk of ICD appropriate therapies (HR=3.8, 95% CI: 1.1–14.3, p=0.035), as well as patients with NSVT and QRSd ≥180 ms (HR=7.2, 95% CI: 1.6–32.7, p=0.003). No patient with severe altered LVEF without other risk factor had appropriate ICD therapy. Patients with congestive heart failure and/or altered LVEF had a higher risk of non-sudden death or cardiac transplantation (HR=14.4, 95% CI: 1.8–112.7, p Conclusions Our data illustrate that specific risk stratification and primary prevention for sudden cardiac death in patients with tetralogy of Fallot may be improved. The value of a severely altered LVEF appears low in the absence of other risk factors, and combination of different predictors is essential. The high rate of complications as well as consideration of competing risk situation have to be integrated in the benefit-risk equation.

An ancestral inversion of 900 kb on chromosome 17q21, which includes the microtubule-associated protein tau (MAPT) gene, defines two haplotype clades in Caucasians (H1 and H2). The H1 haplotype has been linked inconsistently with AD. In a previous study, we showed that an SNP tagging this haplotype (rs1800547) was associated with AD risk in a large population from the Dementia Genetics Spanish Consortium (DEGESCO) including 4435 cases and 6147 controls. The association was mainly driven by individuals that were non-carriers of the APOE epsilon 4 allele. Our aim was to replicate our previous findings in an independent sample of 4124 AD cases and 3290 controls from Spain (GR@ACE project) and to analyze the effect of the H1 sub-haplotype structure on the risk of AD. The H1 haplotype was associated with AD risk (OR = 1.12; p = 0.0025). Stratification analysis showed that this association was mainly driven by the APOE epsilon 4 non-carriers (OR = 1.15; p = 0.0022). Pooled analysis of both Spanish datasets (n = 17,996) showed that the highest AD risk related to the MAPT H1/H2 haplotype was in those individuals that were the oldest [third tertile (>77 years)] and did not carry APOE epsilon 4 allele (p = 0.001). We did not find a significant association between H1 sub-haplotypes and AD. H1c was nominally associated but lost statistical significance after adjusting by population sub-structure. Our results are consistent with the hypothesis that genetic variants linked to the MAPT H1/H2 are tracking a genuine risk allele for AD. The fact that this association is stronger in APOE epsilon 4 non-carriers partially explains previous controversial results and might be related to a slower alternative causal pathway less dependent on brain amyloid load., ` The Genome Research at Fundacio ACE/Dementia Genetics Spanish Consortium (GR@ACE/DEGESCO) would like to thank patients and controls who participated in this project. GR@ACE/DEGESCO GWAS program was funded by Grifols SA, Fundacion Bancaria La Caixa, and Fundacio ACE, Institut Catala de Neurociencies Aplicades. PS-J and AR have also received support by grant PI16/01861. Accion Estrategica en Salud integrated in the Spanish National I CD Ci Plan and financed by Instituto de Salud Carlos III (ISCIII) - Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER - Una Manera de Hacer Europa). PS-J was supported by IDIVAL, Instituto de Salud Carlos III [Fondo de Investigacion Sanitario, PI08/0139, PI12/02288, PI16/01652, JPND (DEMTEST PI11/03028)], and the CIBERNED program. We thank Biobanco Valdecilla for their support. LM was supported by Consejeria de Salud de la Junta de Andalucia (Grant PI-0001/2017). DEGESCO was also sponsored by the Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain). Control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III (www.bancoadn.org, University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain) and they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. The genotyping service to generate GR@ACE/DEGESCO GWAS data was carried out at CEGEN-PRB3-ISCIII; it was supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. GR@ACE/DEGESCO consortia would also like to thank to all researchers contributing to this project. A complete list of collaborators involved in the GR@ACE/DEGESCO GWAS can be found at https://ciberned.es/proyectos/degesco.html.

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.

An ancestral inversion of 900 kb on chromosome 17q21, which includes the microtubule-associated protein tau (MAPT) gene, defines two haplotype clades in Caucasians (H1 and H2). The H1 haplotype has been linked inconsistently with AD. In a previous study, we showed that an SNP tagging this haplotype (rs1800547) was associated with AD risk in a large population from the Dementia Genetics Spanish Consortium (DEGESCO) including 4435 cases and 6147 controls. The association was mainly driven by individuals that were non-carriers of the APOE epsilon 4 allele. Our aim was to replicate our previous findings in an independent sample of 4124 AD cases and 3290 controls from Spain (GR@ACE project) and to analyze the effect of the H1 sub-haplotype structure on the risk of AD. The H1 haplotype was associated with AD risk (OR = 1.12; p = 0.0025). Stratification analysis showed that this association was mainly driven by the APOE epsilon 4 non-carriers (OR = 1.15; p = 0.0022). Pooled analysis of both Spanish datasets (n = 17,996) showed that the highest AD risk related to the MAPT H1/H2 haplotype was in those individuals that were the oldest [third tertile (>77 years)] and did not carry APOE epsilon 4 allele (p = 0.001). We did not find a significant association between H1 sub-haplotypes and AD. H1c was nominally associated but lost statistical significance after adjusting by population sub-structure. Our results are consistent with the hypothesis that genetic variants linked to the MAPT H1/H2 are tracking a genuine risk allele for AD. The fact that this association is stronger in APOE epsilon 4 non-carriers partially explains previous controversial results and might be related to a slower alternative causal pathway less dependent on brain amyloid load.

International audience; Concrete is widely used in nuclear facilities (Nuclear Power Plants, Deep Geological Repository) andparticipate to ensure their safety. Aging may deeply impact the mechanical and containment properties ofstructures made ofeither concrete orreinforced concrete. Present knowledge regarding concrete pathologiesis mainly based upon small-scale and separate effect experiments at laboratory level. Within this context,IRSN started the ODOBA international program. Its main objective is to improve the understanding ofphenomena related to aging, to assess and qualify Non Destructive Examination and to develop and validatenumerical models to predict pathologies evolutions at structural scale. ODOBA experimentation is mainlyperformed in Cadarache (South-East of France) on the ODE platform and consists oflarge-scale concretespecimenspecimen, highly instrumented. As today, 17 specimens representing containment building issue,were cast. DEF, ASR and coupled ASR/DEF are studied. The majority ofthe specimens will be submittedto accelerated aging by immersion in heated water pool. Some specimenspecimens are reinforced with steel rebars. First deformations are foreseen at the beginning of 2020. Today, ODOBA partners include USNRC, CNSC (Canada), Bel V (Belgium), VTT (Finland) and NRA (Japan). NSC (China) should soon sign the ODOBA agreements.

Background Ventricular arrhythmias and sudden death are potential late complications in patients with tetralogy of Fallot. Data regarding the value of implantable cardioverter defibrillators (ICD) are scarce in this population. Purpose To assess long-term rates of appropriate ICD therapies and ICD-related complications in a large registry. Methods The DAI-T4F study is an ongoing national French registry including all patients with tetralogy of Fallot and ICD ( NCT03837574 ). Information has been collected prospectively since 2010 with annual update. Cox proportional hazard models were used to identify factors associated with appropriate ICD therapies and complications. Results A total of 134 patients (median age 41.7 years, 70.7% males) were enrolled, including 47 (35.1%) for primary prevention. The median (IQR) follow-up duration was 6.1 (2.7–10.2) years. Overall, 14 (29.8%) and 45 (51.7%) patients received at least one appropriate ICD therapy in primary and secondary prevention, respectively, giving annual incidences of 5.5% and 7.1% (P = 0.06). Patients with altered left ventricle ejection fraction (LVEF) at inclusion ≤ 35% experienced less appropriate ICD therapies (HR = 0.31, 95% CI: 0.11-0.86, P = 0.02), whereas a history of sustained or non-sustained ventricular arrhythmia (HR = 2.7, 95% CI: 1.2–3.9, P = 0.03) was positively associated with appropriate therapies. Fifty-seven (42.5%) patients had ICD-related complications, including 32 (24.2%) inappropriate ICD shocks. During follow-up, 7 (5.2%) patients underwent cardiac transplantation and 12 (9.0%) patients died, mainly from progressive heart failure (n = 5). Only one sudden death due to electrical storm was recorded ( Fig. 1 ). Conclusions Appropriate therapies are frequent in patients with tetralogy of Fallot and ICDs, including in primary prevention. The relatively important proportion of ICD-related complication highlights the need for improving risk stratification in this population.