Author: "Hagège, A." / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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211 results on '"Hagège, A."'

1. Genome-wide association study reveals novel genetic loci

Author: Carolina Roselli, Mengyao Yu, Victor Nauffal, Adrien Georges, Qiong Yang, Katie Love, Lu Chen Weng, Francesca N Delling, Svetlana R Maurya, Maren Schrölkamp, Jacob Tfelt-Hansen, Albert Hagège, Xavier Jeunemaitre, Stéphanie Debette, Philippe Amouyel, Wyliena Guan, Jochen D Muehlschlegel, Simon C Body, Svati Shah, Zainab Samad, Sergiy Kyryachenko, Carol Haynes, Michiel Rienstra, Thierry Le Tourneau, Vincent Probst, Ronan Roussel, Inez J Wijdh-Den Hamer, Joylene E Siland, Kirk U Knowlton, Jean Jacques Schott, Robert A Levine, Emelia J Benjamin, Ramachandran S Vasan, Benjamin D Horne, Joseph B Muhlestein, Giovanni Benfari, Maurice Enriquez-Sarano, Andrea Natale, Sanghamitra Mohanty, Chintan Trivedi, Moore B Shoemaker, Zachary T Yoneda, Quinn S Wells, Michael T Baker, Eric Farber-Eger, Hector I Michelena, Alicia Lundby, Russell A Norris, Susan A Slaugenhaupt, Christian Dina, Steven A Lubitz, Nabila Bouatia-Naji, Patrick T Ellinor, David J Milan, and Cardiovascular Centre (CVC)
Subjects: Adult, Proteomics, Mitral Valve Prolapse, Latent TGF-beta Binding Proteins, Genetic Loci, Risk Factors, Translational Research, Humans, Mitral Valve Insufficiency, Cardiology and Cardiovascular Medicine, Genome-Wide Association Study
Abstract: AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder.METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors.CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-β signalling molecules and spectrin β. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.KEY QUESTION: Expand our understanding of the genetic basis for mitral valve prolapse (MVP). Uncover relevant pathways and target genes for MVP pathophysiology. Leverage genetic data for MVP risk prediction.KEY FINDING: Sixteen genetic loci were significantly associated with MVP, including 13 novel loci. Interesting target genes at these loci included LTBP2, TGFB2, ALKP3, BAG3, RBM20, and SPTBN1. A risk score including clinical factors and a polygenic risk score, performed best at predicting MVP, with an area under the receiver operating characteristics curve of 0.677.TAKE-HOME MESSAGE: Mitral valve prolapse has a polygenic basis: many genetic variants cumulatively influence pre-disposition for disease. Disease risk may be modulated via changes to transforming growth factor-β signalling, the cytoskeleton, as well as cardiomyopathy pathways. Polygenic risk scores could enhance the MVP risk prediction.
Published: 2022
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2. Health, illness and cancer in Mayotte: Multicultural experiences in a medically underserved French Territory

Author: Meoïn Hagège, Anrifia Ali-Hamadi, Stéphanie Oddou, Roger Serhal, Team Isocarma, Magdalena Klass, and Mohamed Khettab
Subjects: Health Services Needs and Demand, Cancer Research, Undocumented Immigrants, Medically Underserved Area, Social Sciences, Uterine Cervical Neoplasms, Cultural Diversity, Hematology, General Medicine, Emigration and Immigration, Comoros, Socioeconomic Factors, Oncology, Health, Humans, Mass Screening, Disease, Female, Radiology, Nuclear Medicine and imaging, Health Facilities, Healthcare Disparities
Abstract: The island of Mayotte is part of the French territory and one of the European Union's Outermost Regions but there is a significant lack of data and research on health and cancers in Mayotte. This article reviews the literature on health, disease and cancer in Mayotte, from the perspectives of social science and epidemiology. It starts by shedding light on the specificities of Mahoran demography and society, and shows the healthcare infrastructure is insufficient to meet the population's needs. It then reviews social science studies on health and illness in Mayotte and shows that the political issue of migration permeates the management and the experiences of health on the island. It ends with a focus on the epidemiology of cervical cancer and a review of the available data on screening, treatment and prevention. The article concludes with a quick review of ongoing research and urgently calls for more data and research on this critical public health issue.
Published: 2022
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3. Aetiological classification and prognosis in patients with heart failure with preserved ejection fraction

Author: Orianne Domengé, Albert A. Hagège, Michel Azizi, Etienne Puymirat, Elie Mousseaux, Mariana Mirabel, Laurence Amar, Anne-Sophie Jannot, Jean-Sébastien Hulot, Jean-Baptiste Carves, Eva Vermersch, Anne Blanchard, Claire Carette, Maxime Wack, Marine Livrozet, Julien Le Guen, Alexandre Karras, Marie-Cécile Bories, Antoine Fayol, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Jannot, Anne-Sophie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: medicine.medical_specialty, Heart failure with preserved ejection faction, [SDV]Life Sciences [q-bio], Comorbidity, Aetiologies, 030204 cardiovascular system & hematology, Ventricular Function, Left, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Medicine, Humans, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, 10. No inequality, Heart Failure, Ejection fraction, business.industry, Proportional hazards model, Medical record, Mortality rate, Stroke Volume, Original Articles, medicine.disease, Prognosis, Classification, Obesity, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, [SDV] Life Sciences [q-bio], Heart failure, RC666-701, Etiology, Cardiology, Female, Original Article, Cardiology and Cardiovascular Medicine, Heart failure with preserved ejection fraction, business
Abstract: Aims Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various causes that may influence prognosis. Methods and results We extracted the electronic medical records for 2180 consecutive patients hospitalized between 2016 and 2019 for decompensated heart failure. Using a text mining algorithm looking for a left ventricular ejection fraction ≥50% and plasma brain natriuretic peptide level >100 pg/mL, we identified 928 HFpEF patients. We screened for a prevailing cause of HFpEF according to European guidelines and found that 418 (45.0%) patients had secondary HFpEF due to either myocardial (n = 125, 13.5%) or loading condition abnormalities (n = 293, 31.5%), while the remaining 510 (55.0%) patients had idiopathic HFpEF. We assessed the association between the causes of HFpEF and survival collected up to 31 December 2020 using Cox proportional hazards analysis. Even though patients with idiopathic HFpEF were older, frequently female, and had frequent co‐morbidities and a higher crude mortality rate compared with secondary HFpEF patients, their prognosis was similar after adjustment for age and sex. Unsupervised clustering analysis revealed three main phenogroups with different distribution of idiopathic vs. secondary HFpEF. The phenogroup with the highest proportion of idiopathic HFpEF (69%) had (i) an excess rate of non‐cardiac co‐morbidities including chronic obstructive pulmonary disease (31%) or obesity (41%) and (ii) a better prognosis compared with the two other phenogroups enriched with secondary HFpEF. Conclusions Aetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF., Condensed abstract The identification of specific aetiologies was possible in almost half of patients with heart failure with preserved ejection fraction (HFpEF). Compared with patients with secondary HFpEF, patients with idiopathic HFpEF were older, frequently female, and had a higher proportion of co‐morbidities and high crude mortality rates, but their prognosis was similar after adjustment for age and sex. Unsupervised cluster analysis, however, indicated that idiopathic HFpEF patients were mostly grouped into separate cluster with a better prognosis. Aetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF.
Published: 2022
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4. Motivation to pursue anti-TNFα treatment in patients with Crohn's disease – the SPACE motivation study

Author: Ferdinando D'Amico, Laurent Peyrin-Biroulet, Hervé Hagège, Luc Vandromme, Maria Nachury, Salim Benkhalifa, Xavier Hébuterne, Patrick Faure, Yoram Bouhnik, Stéphane Nahon, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Humanitas University [Milan] (Hunimed), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Polyclinique Courlancy (PC), Polyclinique de Courlancy, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Clinique Pasteur, Clinique Pasteur [Toulouse], Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), AbbVie, CHU Lille, Service de Gastro-entérologie et Nutrition[Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut des Maladies de l'Appareil Digestif, and Université de Nantes (UN)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Disease, Satisfaction of patients with Crohn's disease questionnaire (SPACE-Q), Treatment satisfaction, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Surveys and Questionnaires, Internal medicine, medicine, Adalimumab, Humans, Treatment adherence, In patient, Longitudinal Studies, Prospective Studies, Prospective cohort study, Motivation, Crohn's disease, Hepatology, business.industry, Anti-tumor necrosis factor α, Gastroenterology, Middle Aged, medicine.disease, Infliximab, Chronic disorders, 3. Good health, Treatment Outcome, Patient Satisfaction, 030220 oncology & carcinogenesis, Linear Models, Female, Tumor Necrosis Factor Inhibitors, 030211 gastroenterology & hepatology, France, business, medicine.drug
Abstract: International audience; Background: Crohn's disease (CD) is a chronic disorder requiring long-term treatment. However, up to 20% of patients interrupt temporarily or permanently anti-TNFα. Primary aim was to identify internal and external factors influencing patient's motivation to pursue anti-TNFα in active CD.Methods: This was a French, multicentre, prospective study enrolling CD patients on anti-TNFα therapy since more than 3 months. Patients completed the Satisfaction of Patients with Crohn's Disease questionnaire (SPACE-Q) and other patient-reported-outcome tools at inclusion visit, and after 6 and 12 months.Results: A total of 274 patients were included: 146 (53.3%) received adalimumab, while 128 (46.7%) infliximab. Most patients (78%) were still treated with anti-TNFα 12 months after enrolment. Patients' perception of necessity (p = 0.01) and concerns (p
Published: 2020
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5. CE-ICP-MS to probe Aβ1-42/copper (II) interactions, a complementary tool to study amyloid aggregation in Alzheimer's disease

Author: C Duroux and A Hagège
Subjects: Biomaterials, Amyloid beta-Peptides, Alzheimer Disease, Chemistry (miscellaneous), Metals and Alloys, Biophysics, Humans, Biochemistry, Copper, Peptide Fragments
Abstract: Copper (II) ions appear to be involved in the Alzheimer's disease and seem to influence the aggregation of the amyloid-β1-42 (Aβ1-42) peptide. However, data are not conclusive and still not subject to consensus, copper (II) being suspected to either promote or inhibit aggregation. To address this question, CE-ICP-MS (capillary electrophoresis-inductively coupled plasma-mass spectrometry) hyphenation was proposed as a complementary tool to follow the distribution of copper in the different oligomeric forms, at different substoichiometries and different incubation times. Results clearly indicated the formation of several negatively charged copper complexes and showed the enhancement of the aggregation rate with copper concentration. Moreover, the variations of copper (II) speciation suggest different aggregation pathway, even for substoichiometric ratios.
Published: 2021
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6. Health, illness and cancer in Reunion Island: Health services in a diverse but aging French territory

Author: Meoïn Hagège, Emmanuel Chirpaz, and Mohamed Khettab
Subjects: Male, Cancer Research, Health Services Needs and Demand, Research, Prostatic Neoplasms, Uterine Cervical Neoplasms, Breast Neoplasms, Hematology, General Medicine, Cultural Diversity, Health Services, Oncology, Socioeconomic Factors, Health Transition, Neoplasms, Chronic Disease, Humans, Radiology, Nuclear Medicine and imaging, Disabled Persons, Female, Reunion, Needs Assessment
Abstract: The major social, cultural, economic and demographic changes in Reunion Island in the last 70 years have had effects on its population and the evolution of its public health issues. The demographic transition and changes in lifestyle have led to a rapidly aging population with increased needs for care for dependency and chronic illness such as cancers. The aim of this paper is to offer a review of the literature and ongoing research on health and cancer in Reunion Island. It reviews the recent literature on these changes, including the socio-demography of the population, the medical demography and cancer care infrastructure. It highlights the significant social inequalities of the island, and shows its medical demography and healthcare services are close to national averages. It then offers a review of publications on the experiences of health and illness in Reunion Island in a multicultural and postcolonial context, between medical pluralism and biomedicine. It then offers a focus on the epidemiology of three cancers, namely breast, cervical and prostate cancers. It concludes with a review of known ongoing research, and calls for a rapid adaptation of the organization of the medico-social system, in order to face Reunion Island's most pressing healthcare issues: chronic illnesses such as cancers, and dependency.
Published: 2021

7. Interactions between copper (II) and β-amyloid peptide using capillary electrophoresis-ICP-MS: Kd measurements at the nanogram scale

Author: C, Duroux and A, Hagège
Subjects: Amyloid beta-Peptides, Alzheimer Disease, Electrophoresis, Capillary, Humans, HEPES, Copper
Abstract: Although the interaction between the β-amyloid peptide and copper (II) appears to play an important role in Alzheimer's disease, the affinity constant is still controversial and values are ranging from 10
Published: 2021

8. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

Author: Mélanie Fradin, Nicolas Sadoul, Xavier Waintraub, Didier Klug, Albert Hagège, Pascal Sabouraud, Arnaud Isapof, Julien Durigneux, Olivier Lascols, Pascal Laforêt, Armelle Magot, Ivana Dabaj, Eloi Marijon, Camille Vatier, Pascal Cintas, Emmanuelle Salort, Bénédicte Gaborit, Antoine Muchir, Xavier Ferrer, Pascale Richard, Corinne Metay, Stéphane Boulé, Sarah Leonard-Louis, Philippe Mabo, V. Tiffreau, Caroline Stalens, Jitendra K. Vohra, Stéphane Schaeffer, Khadija Chikhaoui, Eric Bieth, Sandra Mercier, Pierre Ambrosi, Aleksandra Nadaj-Pakleza, Michèle Mayer, Katja Zeppenfeld, Gisèle Bonne, Véronique Manel, Jean-Marc Davy, Guilhem Sole, Ghassan Moubarak, Nicolas Lamblin, Klaus Dieterich, Christophe Meune, Abdallah Fayssoil, Arnaud Lazarus, Philippe Maury, Karim Wahbi, Philippe Petiot, Isabelle Jéru, Annick Toutain, Corinne Vigouroux, Ana Ferreiro, Maud Michaud, H.M. Bécane, Bruno Eymard, Thomas D. Gossios, Marie-Christine Vantyghem, Saurabh Kumar, Estelle Gandjbakhch, Yann Péréon, T. Thompson, Marie-Christine Minot-Myhié, Anthony Behin, Frédéric Sacher, Philippe Charron, Nicolas Combes, Julien Praline, Dominique Babuty, Emmanuelle Lagrue, Usha B. Tedrow, Jean-Marc Sellal, Florence Petit, Perry M. Elliott, Frédéric Anselme, Philippe Chevalier, Frederic Taithe, Christine Barnerias, Vincent Laugel, Andoni Echaniz-Laguna, Raphaël P. Martins, Alexander F.A. Androulakis, Rabah Ben Yaou, Franck Boccara, Ulrike Walther-Louvier, Tanya Stojkovic, Françoise Bouhour, Annachiara De Sandre-Giovannoli, Susana Quijano-Roy, Françoise Chapon, Jean-Noël Trochu, Céline Tard, Anne Rollin, Jean-Marie Cuisset, Denis Duboc, Raphaël Porcher, Catherine Sarret, Jonathan M. Kalman, Florence Demurger, Damien Bonnet, Christine Francannet, Neal K. Lakdawala, Romain Eschalier, Fabien Labombarda, Kostantinos Savvatis, Raul Juntas Morales, Isabelle Desguerre, Nicolas Lévy, Anne-Claire Brehin, Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), St Bartholomew's Hospital (London), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Association française contre les myopathies (AFM-Téléthon), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hôpital Ambroise Paré [AP-HP], William Harvey Research Institute, Barts and the London Medical School, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Filière Neuromusculaire (FILNEMUS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Caen Normandie (UNICAEN), Laboratoire d'Informatique Scientifique et Industrielle (LISI), Université de Poitiers-Ecole Nationale Supérieure de Mécanique et d'Aérotechnique [Poitiers] (ISAE-ENSMA), Hôpital Raymond Poincaré [AP-HP], CHU Lille, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix Marseille Université (AMU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Leiden University Medical Center (LUMC), Universiteit Leiden, Service de neurologie pédiatrique [CHU Necker], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Hôpital Privé Le Bois Ramsay Santé [Lille], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [APHP], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Strasbourg, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Laboratoire d'étude de la motricité humaine - EA 3608 (LEMH), Université de Lille, Droit et Santé, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), The Heart Hospital [London], University College of London [London] (UCL), This study was funded by grants from the AFM-Téléthon (French Alliance against Myopathies), which was not involved in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. Some of this work was undertaken at University College London (United Kingdom) and St. Bartholomew’s Hospital (London, United Kingdom), which received a portion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Laboratoire d'Informatique Scientifique et Industrielle (LISI / ENSMA), LISI-ENSMA, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Unité de Cardiologie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital neurologique, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service Neurologie Pédiatrique, Service de Neuropédiatrie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Département de Neurologie, Hôpital Civil de Strasbourg, Groupe Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale, CHU - HÔTEL-DIEU Clermont-Ferrand, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Clinique Ambroise Paré, CHU Cochin [AP-HP], Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hopital Neurologique-Hôpital Femme Mère Enfant, Department of Medicine, Columbia University [New York]-College of Physicians and Surgeons, Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpital de Rangueil, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'étude de la motricité humaine (LEMH EA3608), Université de Montréal - UdeM (CANADA), Laboratoire Génie des procédés papetiers (LGP2), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hôpital Purpan [Toulouse], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Tachycardia, medicine.medical_specialty, implantable, Accurate estimation, Ventricular Tachyarrhythmias, Validation Studies as Topic, 030204 cardiovascular system & hematology, tachycardia, Sudden death, LMNA, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, death, Physiology (medical), Internal medicine, defibrillators, medicine, Humans, In patient, 030212 general & internal medicine, sudden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Prediction score, business.industry, Defibrillators, Implantable, ventricular, Tachycardia, Ventricular, Cardiology, Female, medicine.symptom, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract: Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.
Published: 2019
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9. FLNC pathogenic variants in patients with cardiomyopathies: Prevalence and genotype‐phenotype correlations

Author: Ader, Flavie, De Groote, Pascal, Réant, Patricia, Rooryck-Thambo, Caroline, Dupin-Deguine, Delphine, Rambaud, Caroline, Khraiche, Diala, Perret, Claire, Pruny, Jean François, Mathieu-Dramard, Michele, Gérard, Marion, Troadec, Yann, Gouya, Laurent, Jeunemaitre, Xavier, Van Maldergem, Lionel, Hagège, Albert, Villard, Eric, Charron, Philippe, Richard, Pascale, Rooryck‐Thambo, Caroline, Dupin‐Deguine, Delphine, Mathieu‐Dramard, Michèle, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Adaptation cardiovasculaire à l'ischemie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Service de génétique médicale, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Stress Abiotiques et Différenciation des Végétaux Cultivés (SADV), Université de Lille, Sciences et Technologies-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de génétique médicale et oncogénétique [CHU Amiens Picardie], CHU Amiens-Picardie, Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Therapie Cellulaire en Pathologie Cardio-Vasculaire (UMR_S 633), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), gerard, marion, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Recherche Agronomique (INRA)-Université de Lille, Sciences et Technologies, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Montréal - UdeM (CANADA), Université de Montréal (UdeM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre de Génétique Moléculaire et Chromosomique du GH Pitié-Salpêtrière-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Service d'Anatomie Pathologique et Médecine Légale, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Raymond Poincaré [Garches], Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bichat, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Paris - UFR Sciences Fondamentales et Biomédicales [Sciences], Université de Paris (UP), Hôpital Raymond Poincaré [AP-HP], Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cardiologie [CHU Pitié-Salpêtrière], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Male, cardiomyopathies, 0301 basic medicine, Genotype-phenotype correlation, Genotype, Filamins, Cardiomyopathy, [SDV.GEN] Life Sciences [q-bio]/Genetics, 030105 genetics & heredity, Sudden cardiac death, Electrocardiography, 03 medical and health sciences, Prevalence, Genetics, medicine, Humans, Missense mutation, Genetic Predisposition to Disease, Genetic Testing, FLNC, Indel, Alleles, Genetic Association Studies, Genetics (clinical), next generation sequencing, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Genetic Variation, High-Throughput Nucleotide Sequencing, Dilated cardiomyopathy, Sequence Analysis, DNA, medicine.disease, Magnetic Resonance Imaging, Phenotype, Pedigree, 3. Good health, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Echocardiography, Mutation, Female, business, myopathy
Abstract: International audience; Pathogenic variants in FLNC encoding filamin C have been firstly reported to cause myopathies, and were recently linked to isolated cardiac phenotypes. Our aim was to estimate the prevalence of FLNC pathogenic variants in subtypes of cardiomyopathies and to study the relations between phenotype and genotype. DNAs from a cohort of 1150 unrelated index-patients with isolated cardiomyopathy (700 hypertrophic, 300 dilated, 50 restrictive cardiomyopathies, and 100 left ventricle non-compactions) have been sequenced on a custom panel of 51 cardiomyopathy disease-causing genes. An FLNC pathogenic variant was identified in 28 patients corresponding to a prevalence ranging from 1% to 8% depending on the cardiomyopathy subtype. Truncating variants were always identified in patients with dilated cardiomyopathy, while missense or in-frame indel variants were found in other phenotypes. A personal or family history of sudden cardiac death (SCD) was significantly higher in patients with truncating variants than in patients carrying missense variants (P = .01). This work reported the first observation of a left ventricular non-compaction associated with a unique probably causal variant in FLNC which highlights the role of FLNC in cardiomyopathies. A correlation between the nature of the variant and the cardiomyopathy subtype was observed as well as with SCD risk.
Published: 2019
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10. Including older patients in cancer trials: A qualitative study of collaboration between geriatricians and oncologists

Author: Florence Canoui-Poitrine, Benjamin Derbez, Meoïn Hagège, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, AP-HP, hôpital Henri-Mondor, Department of Public Health, F-94010 Creteil, France, Université Paris 8 Vincennes-Saint-Denis (UP8), CRESPPA-CSU, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cultures et sociétés urbaines (Cresppa-CSU), Centre de recherches sociologiques et politiques de Paris (CRESPPA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS), Cultures et sociétés urbaines (CSU), and Université Paris 8 Vincennes-Saint-Denis - UFR Textes et sociétés (UP8 UFR TS)
Subjects: medicine.medical_specialty, Best practice, [SDV.CAN]Life Sciences [q-bio]/Cancer, Medical Oncology, law.invention, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Continuing medical education, law, Neoplasms, Medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Aged, Cancer, Geriatrics, Oncologists, clinical trials, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Geriatricians, 3. Good health, Clinical trial, inclusion, Oncology, Geriatric oncology, 030220 oncology & carcinogenesis, Family medicine, Observational study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Geriatrics and Gerontology, business, Qualitative research
Abstract: Background The under-representation of older patients in cancer trials remains an important obstacle to the generation of data on efficacy and safety in this growing patient population. In France, geriatric oncology coordination units (UCOGs) have been created to help oncologists and geriatricians work together on research, best practice, and continuing medical education. Taking these units as a case study, this paper sheds light on the collaboration between geriatricians and oncologists in the inclusion process of older patients in cancer trials. Materials and Methods Empirical data were gathered in a series of sociological interviews with all 16 oncologists, geriatricians and unit coordinators in the five UCOGs in the greater Paris region of France. Results The case of French geriatric oncology coordination units shows the gap between professional research cultures in oncology and geriatrics that may account for the low observed inclusion rates. It is easier to include patients in randomized clinical trials than in observational studies. UCOGs have the potential to improve research in geriatric oncology by catalyzing the development and implementation of effective collaboration tools (such as frailty assessments). The units also have the potential to promote Phase IV trials and observational research that are suitable for older patients with cancer. Discussion Bridging the cultural gap between oncologists (the dominant force in setting the cancer research agenda) and geriatricians (a source of specific knowledge and know-how) is essential for producing relevant trial protocols that match the specific yet diverse features of older patient populations.
Published: 2021
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11. Feasibility and Performance of Noninvasive Ultrasound Therapy in Patients With Severe Symptomatic Aortic Valve Stenosis: A First-in-Human Study

Author: Albert A. Hagège, Alexander Ijsselmuiden, Samuel Zarka, René Spaargaren, Mathieu Pernot, B. Ren, Selina Vlieger, Mathieu Rémond, Emmanuel Messas, Benjamin Bertrand, Guillaume Goudot, Bernard Cholley, Christian Spaulding, Peter den Heijer, Mickael Tanter, Robin Penot, Etienne Puymirat, and Eloi Marijon
Subjects: Male, medicine.medical_specialty, Ultrasonic Therapy, Severity of Illness Index, Physiology (medical), medicine.artery, Internal medicine, medicine, Humans, In patient, Aged, Aged, 80 and over, Aorta, business.industry, Ultrasound, First in human, Aortic Valve Stenosis, medicine.disease, Treatment Outcome, Echocardiography, Aortic valve stenosis, Aortic Valve, Cardiology, Feasibility Studies, Female, Cardiology and Cardiovascular Medicine, business
Published: 2021

12. Low doses of uranium and osteoclastic bone resorption: key reciprocal effects evidenced using new in vitro biomimetic models of bone matrix

Author: Christophe Den Auwer, Gaëlle Creff, Sophie Pagnotta, Bastien Simoneau, Sabine Santucci-Darmanin, François Orange, Georges F. Carle, Tatiana Gritsaenko, Xavier Jaurand, Agnès Hagège, Delphine Farlay, Valérie Pierrefite-Carle, UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Institut de Chimie de Nice (ICN), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Separative Methods - Techniques séparatives, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), CCMA - Centre Commun de Microscopie Appliquée, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre Technologique des Microstructures (CTµ), Université de Lyon-Université de Lyon, The author’s lab work was funded by Université Côte d’Azur (UCA) and grants from the CEA ('Programme Transversal de Toxicologie Nucléaire') and the ANR (ANR-16-CE34-0003-01). CCMA electron microscopy equipments have been funded by the Région Sud PACA, the Conseil Départemental des Alpes Maritimes and the GIS-IBiSA., ANR-16-CE34-0003,TURBO,Toxicité de l'uranium: Approche multi-échelles du processus de biomineralisation dans les os(2016), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Separative Methods - Techniques séparatives (TechSep), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bussy, Agnès, Toxicité de l'uranium: Approche multi-échelles du processus de biomineralisation dans les os - - TURBO2016 - ANR-16-CE34-0003 - AAPG2016 - VALID, Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université Côte d'Azur (UCA), and Université de Lyon
Subjects: 0301 basic medicine, inorganic chemicals, Health, Toxicology and Mutagenesis, chemistry.chemical_element, Bone Matrix, Osteoclasts, 010501 environmental sciences, Toxicology, Bone tissue, 01 natural sciences, Models, Biological, complex mixtures, Bone resorption, 03 medical and health sciences, chemistry.chemical_compound, Mice, Biomimetic models, Osteoclast, Biomimetics, Cell Line, Tumor, Bone cell, medicine, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Tissue Distribution, Bone Resorption, Bone, 0105 earth and related environmental sciences, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Uranium phosphate, technology, industry, and agriculture, General Medicine, Environmental exposure, Natural uranium, Uranium, Extracellular Matrix, Resorption, [SDV.TOX] Life Sciences [q-bio]/Toxicology, 030104 developmental biology, medicine.anatomical_structure, RAW 264.7 Cells, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Biophysics
Abstract: The authors would like to thank Chantal Cros and Colette Ricort for helpful technical assistance. The authors acknowledge the MARS beamline of SOLEIL synchrotron (Gif sur Yvette, France) that was used to perform XAS experiments and the IRCAN's Molecular and Cellular Core Imaging (PICMI) Facility which is supported by grants from the Ministère de l’Enseignement Supérieur, the Région PACA, the Conseil Départemental des Alpes Maritimes, INSERM, the FEDER, the GIS IBiSA, the Canceropole PACA and the foundation ARC.Funding; International audience; Uranium is widely spread in the environment due to its natural and anthropogenic occurrences, hence the importance of understanding its impact on human health. The skeleton is the main site of long-term accumulation of this actinide. However, interactions of this metal with biological processes involving the mineralized extracellular matrix and bone cells are still poorly understood. To get a better insight into these interactions, we developed new biomimetic bone matrices containing low doses of natural uranium (up to 0.85 µg of uranium per cm2). These models were characterized by spectroscopic and microscopic approaches before being used as a support for the culture and differentiation of pre-osteoclastic cells. In doing so, we demonstrate that uranium can exert opposite effects on osteoclast resorption depending on its concentration in the bone microenvironment. Our results also provide evidence for the first time that resorption contributes to the remobilization of bone matrix-bound uranium. In agreement with this, we identified, by HRTEM, uranium phosphate internalized in vesicles of resorbing osteoclasts. Thanks to the biomimetic matrices we developed, this study highlights the complex mutual effects between osteoclasts and uranium. This demonstrates the relevance of these 3D models to further study the cellular mechanisms at play in response to uranium storage in bone tissue, and thus better understand the impact of environmental exposure to uranium on human bone health.
Published: 2021
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13. Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)

Author: Barré, Tangui, Pol, Stanislas, Ramier, Clémence, Di Beo, Vincent, Carrat, Fabrice, Bureau, Morgane, Bourlière, Marc, Dorival, Céline, Serfaty, Lawrence, Asselah, Tarik, Boursier, Jérôme, Marcellin, Fabienne, Carrieri, Patrizia, Fontaine, Hélène, Protopopescu, Camelia, Alric, Laurent, Bonnet, Delphine, Payssan-Sicart, Virginie, Pomes, Chloe, Zoulim, Fabien, Maynard, Marianne, Bai, Roxane, Hucault, Lucie, Bailly, François, Raffi, François, Billaud, Eric, Boutoille, David, Lefebvre, Maeva, André-Garnier, Elisabeth, Cales, Paul, Hubert, Isabelle, Lannes, Adrien, Lunel, Françoise, Boyer, Nathalie, Giuily, Nathalie, Castelnau, Corinne, Scoazec, Giovanna, Rousseaud, Emilie, Vallet-Pichard, Anaïs, Sogni, Philippe, Ledinghen, Victor De, Foucher, Juliette, Hiriart, Jean-Baptiste, M'Bouyou, Jancell, Irlès-Depé, Marie, Si Ahmed, Si Nafa, Oules, Valérie, Tran, Albert, Anty, Rodolphe, Gelsi, Eve, Truchi, Régine, Thabut, Dominique, Hammeche, Saloua, Moussali, Joseph, Causse, Xavier, Dieuleveult, Barbara De, Ouarani, Brahim, Labarrière, Damien, Ganne, Nathalie, Grando-Lemaire, Véronique, Nahon, Pierre, Brulé, Séverine, Ulker, Betul, Guyader, Dominique, Jezequel, Caroline, Brener, Audrey, Laligant, Anne, Rabot, Aline, Renard, Isabelle, Habersetzer, François, Baumert, Thomas, Doffoel, Michel, Mutter, Catherine, Simo-Noumbissie, Pauline, Razi, Esma, Bronowicki, Jean-Pierre, Barraud, Hélène, Bensenane, Mouni, Nani, Abdelbasset, Hassani-Nani, Sarah, Bernard, Marie-Albertine, Pageaux, Georges-Philippe, Larrey, Dominique, Meszaros, Magda, Metivier, Sophie, Bureau, Christophe, Morales, Thibault, Peron, Jean Marie, Robic, Marie Angèle, Decaens, Thomas, Faure, Marine, Froissart, Bruno, Hilleret, Marie-Noelle, Zarski, Jean-Pierre, Riachi, Ghassan, Goria, Odile, Paris, Fatima, Montialoux, Hélène, Leroy, Vincent, Amaddeo, Giuliana, Varaut, Anne, Simoes, Mélanie, Amzal, Rachida, Chazouillières, Olivier, Andreani, Tony, Angoulevant, Bénédicte, Chevance, Azeline, Samuel, Didier, Antonini, Teresa, Coilly, Audrey, Duclos Vallée, Jean-Charles, Tateo, Mariagrazia, Abergel, Armand, Reymond, Maud, Brigitte, Chanteranne, Benjamin, Buchard, Muti, Léon, Geist, Claire, Conroy, Guillaume, Riffault, Raphaëlle, Rosa, Isabelle, Barrault, Camille, Costes, Laurent, Hagège, Hervé, Loustaud-Ratti, Véronique, Carrier, Paul, Debette-Gratien, Maryline, Mathurin, Philippe, Lassailly, Guillaume, Lemaitre, Elise, Canva, Valérie, Dharancy, Sébastien, Louvet, Alexandre, Minello, Anne, Latournerie, Marianne, Bardou, Marc, Mouillot, Thomas, d'Alteroche, Louis, Barbereau, Didier, Nicolas, Charlotte, Elkrief, Laure, Jaillais, Anaïs, Gournay, Jérôme, Chevalier, Caroline, Archambeaud, Isabelle, Habes, Sarah, Portal, Isabelle, Gelu-Simeon, Moana, Saillard, Eric, Lafrance, Marie-Josée, Catherine, Lucie, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital de Hautepierre [Strasbourg], Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and BOURGEAIS, Véronique
Subjects: Hepatitis B virus, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Aucun, Overweight, medicine.disease_cause, Virus, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Internal medicine, medicine, Humans, Pharmacology (medical), Obesity, ComputingMilieux_MISCELLANEOUS, Cannabis, 030304 developmental biology, Pharmacology, 0303 health sciences, biology, Cannabinoids, business.industry, Liver Neoplasms, Hepatitis B, biology.organism_classification, medicine.disease, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], Complementary and alternative medicine, Hepatocellular carcinoma, Cohort, cannabis, obesity, overweight, socioeconomic status, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract: International audience; Background: Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are available for HBV-infected patients.Aims: We aimed to identify risk factors (including cannabis use) for overweight and obesity in patients with HBV chronic infection.Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we performed two separate analyses, one using “central obesity” (based on waist circumference) and the other “overweight” and “obesity” (based on body mass index) as outcomes. Logistic and multinomial regressions were used to model central obesity and overweight/obesity, respectively.Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively.Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population.
Published: 2021
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14. PresbyPRK vs presbyLASIK using the SUPRACOR algorithm and micromonovision in presbyopic hyperopic patients: visual and refractive results at 12 months

Author: Morfeq Hussein, Boucenna William, Jany Benjamin, Froussart-Maille Françoise, Hagège Alain, Lussato Mikhael, Delbarre Maxime, and Kochbati Elias
Subjects: Binocular distance, Distance visual acuity, Visual acuity, genetic structures, medicine.medical_treatment, Keratomileusis, Laser In Situ, Spherical equivalent, Keratomileusis, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Dioptre, Retrospective Studies, Vision, Binocular, business.industry, Corneal Topography, Mean age, Presbyopia, Middle Aged, eye diseases, Sensory Systems, Photorefractive keratectomy, Ophthalmology, Hyperopia, 030221 ophthalmology & optometry, Surgery, Lasers, Excimer, France, medicine.symptom, business, Algorithm, 030217 neurology & neurosurgery, Algorithms
Abstract: PURPOSE To compare the visual outcome and refractive results between presbyopic photorefractive keratectomy (presbyPRK) and presbyopic laser in situ keratomileusis (presbyLASIK) in presbyopic hyperopic patients using micromonovision and the SUPRACOR algorithm. SETTING Percy Military Hospital and private Laser Victor Hugo Center, France. DESIGN Observational retrospective nonrandomized. METHODS Twenty-three patients who had undergone presbyPRK or presbyLASIK were included and followed up for 12-months. Far and near visual acuity without correction in monocular and binocular, measurement of distance visual acuity with correction in monocular, evaluation of spherical equivalent (SE), aberrometry, and patient satisfaction were measured and analyzed in this study. RESULTS The study included 26 eyes of 13 patients in the presbyLASIK group and 20 eyes of 10 patients in the presbyPRK group. The mean age was 55.43 ± 4.6 years. Uncorrected binocular distance visual acuity was 0.030 ± 0.05 logMAR in the presbyLASIK group and 0 logMAR in the presbyPRK group (P = .066). Binocular near visual acuity without correction was 0.21 ± 0.11 logMAR in the presbyLASIK group and 0.30 ± 0.15 logMAR in the presbyPRK group (P = .0398). For the dominant eyes, the SE was -0.08 ± 0.48 diopters (D) in the presbyLASIK group and 0.16 ± 0.82 D in the presbyPRK group (P = .3995). For nondominant eyes, the SE was -0.44 ± 0.50 D in the presbyLASIK group and 0.12 ± 0.65 D in the presbyPRK group (P = .0254). CONCLUSIONS PresbyPRK and presbyLASIK were comparable in efficacy, stability, predictability, and safety. PresbyPRK could be a safe and effective surgical alternative for the hyperopic presbyopic patient.
Published: 2020

15. Promoting patients' rights at the end of life in a geriatric setting in France: The healthcare professionals’ level of knowledge about surrogate decision-makers and advance directives

Author: Jean Paul Rwabihama, Nadia Oubaya, Joël Belmin, Etienne Audureau, Meoïn Hagège, Marie-Thérèse Rabus, Sylvie Bastuji-Garin, De Rozier Rakotoarisoa, Elena Paillaud, Hind Benzengli, Gabin Ambime, IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Adult, Patients' rights, medicine.medical_specialty, Surrogate decision-maker, Geriatric care, [SDV]Life Sciences [q-bio], Decision Making, education, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Health care, Humans, Medicine, 030212 general & internal medicine, Aged, Health professionals, business.industry, 030503 health policy & services, General Medicine, Middle Aged, University hospital, Confidence interval, 3. Good health, Death, Cross-Sectional Studies, Patient Rights, Family medicine, Female, France, Advance Directives, 0305 other medical science, business
Abstract: Objective To assess levels of knowledge about patients’ rights, surrogate decision-makers, and advance directives among healthcare professionals at three hospitals in France. Methods A multicenter, cross-sectional study in three geriatric hospitals in the Paris area (France) in 2015. The participants’ level of knowledge was assessed via an 18-item self-questionnaire on surrogate decision-makers, advance directives, and end-of-life decision-making. The characteristics associated with a good level of knowledge were assessed using logistic regression. Results Among the 301 healthcare professionals (median ± standard deviation age: 40.4 ± 10.2 years; women: 73.4 %), only 15.0 % (95 % confidence interval (CI): [19.7–29.5]) correctly answered at least 75 % of the questions on patients’ rights. Respectively 24.6 % [19.7–29.5], 36.5 % [31.1–42.0] and 37.5 % [32.0–43.0] had sufficient knowledge regarding “surrogate decision-maker”, “advance directives”, and “decision-making at the end of life”. In a multivariable analysis, the only factor significantly associated with a good level of knowledge about end-of-life policy was employment in a university hospital, with a non-significant trend for status as a physician. Conclusions Our survey of staff working in geriatric care units highlighted the poor overall level of knowledge about healthcare surrogates and advance directives; the results suggest that additional training in these concepts is required. Practice implications Continuing education of healthcare professionals on advance directives and surrogate decision-maker should be promoted to ensure rights of elderly patients at the end of life.
Published: 2020
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16. Genome-wide association meta-analysis supports genes involved in valve and cardiac development to associate with mitral valve prolapse

Author: Russell A. Norris, Albert A. Hagège, Nabila Bouatia-Naji, Jean-Jacques Schott, Sergiy Kyryachenko, Xavier Jeunemaitre, Philippe Amouyel, Stéphanie Debette, Thierry Le Tourneau, Mengyao Yu, Christian Dina, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Population, Single-nucleotide polymorphism, Genome-wide association study, Disease, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Article, Association, Computational biology, 03 medical and health sciences, 0302 clinical medicine, Genotype, Cardiac valve, Humans, Medicine, Mitral valve prolapse, education, Gene, Biological Specimen Banks, 030304 developmental biology, Genetics, 0303 health sciences, education.field_of_study, business.industry, Heart valve diseases, General Medicine, medicine.disease, United Kingdom, 3. Good health, Minor allele frequency, Meta-analysis, Genetic Loci, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Imputation (genetics), 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: ObjectiveMitral valve prolapse (MVP) is a common cardiac valve disease, which affects 1 in 40 in the general population. Previous GWAS have identified six risk loci for MVP. But these loci explained only partially the genetic risk for MVP. We aim to identify additional risk loci for MVP by adding a dataset from the UK Biobank.Approaches and ResultsWe re-analyzed 1,007/1,469 cases and 479/862 controls from the MVP-France study and the MVP-Nantes study, respectively. We re-imputed genotypes using HRC and TOPMed, and found this latter to perform better in terms of accuracy in the lower ranges of minor allele frequency (MAF) below 0.1. We then incorporated 434 MVP cases and 4,527 controls from the UKBiobank and conducted a meta-analysis GWAS including ∼2000 MVP cases and over 6,800 controls for ∼8 million genotyped or imputed common SNPs (MAF>0.01). We replicated the association on chr2 and now provide a finer association map nearTNS1. We identified three suggestive risk loci, all driven by common variants on Chr1 (SYT2), Chr8 (MSRA), and Chr19 (FBXO46). Gene-based association using MAGMA revealed 15 risk genes for MVP includingGLIS1, TGFB2, ID2, TBX5, MSRA, andDMPK. Extensive functional annotation showed that genes associated with MVP are highly expressed in cardiovascular tissues, especially heart, and are involved in cardiac development and potentially aging.ConclusionsWe report an updated meta-analysis GWAS for MVP using dense imputation coverage and an improved case-control sample. We describe several loci and genes with MVP spanning biological mechanisms highly relevant to MVP, especially during valve and heart development.TOC category - basic and population studiesTOC subcategory - Arteriosclerosis, Thrombosis, and Vascular BiologyHighlightsProvide high coverage meta-analysis of GWAS based on TOPMed imputation involving ∼8 million common variants in ∼2000 MVP patients and ∼6800 controls.Low frequency variant contributed little to the association of the genes mentioned, where the associations were driven by common variantsSeveral association loci involve genes related to cardiac development and potentially aging.
Published: 2020
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17. Prospective follow-up in various subtypes of cardiomyopathies: insights from the ESC EORP Cardiomyopathy Registry

Author: Luigi Tavazzi, Jens Mogensen, Michal Tendera, Alida L.P. Caforio, Aldo P. Maggioni, Eloisa Arbustini, Juan R. Gimeno, Roberto Barriales-Villa, Philippe Charron, Albert Hagège, Cécile Laroche, Perry M. Elliott, Elena Biagini, Aly Saad, Petar M. Seferovic, Aleš Linhart, María Ángeles Espinosa, Juan Pablo Kaski, and Luis R. Lopes
Subjects: Proband, Adult, medicine.medical_specialty, Registry, Adolescent, Cardiomyopathy, Cardiology, MACE, registry, 030204 cardiovascular system & hematology, Chest pain, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Atrial Fibrillation, medicine, Palpitations, Humans, 030212 general & internal medicine, cardiovascular diseases, Prospective Studies, Registries, Heart Failure, business.industry, Health Policy, Atrial fibrillation, Original Articles, medicine.disease, Prognosis, 3. Good health, Arrhythmogenic right ventricular dysplasia, cardiomyopathy, prognosis, Cohort, cardiovascular system, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Cardiomyopathies, Mace, Follow-Up Studies
Abstract: Aims The European Society of Cardiology (ESC) European Observational Research Programme (EORP) Cardiomyopathy Registry is a prospective multinational registry of consecutive patients with cardiomyopathies. The objective of this report is to describe the short-term outcomes of adult patients (≥18 years old). Methods and results Out of 3208 patients recruited, follow-up data at 1 year were obtained in 2713 patients (84.6%) [1420 with hypertrophic (HCM); 1105 dilated (DCM); 128 arrhythmogenic right ventricular (ARVC); and 60 restrictive (RCM) cardiomyopathies]. Improvement of symptoms (dyspnoea, chest pain, and palpitations) was globally observed over time (P Conclusions Despite symptomatic improvement, patients with cardiomyopathies remain prone to major clinical events in the short term. Outcomes were different not only according to cardiomyopathy subtypes but also in relatives vs. index patients, and according to European regions.
Published: 2020
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18. Hypertrophic cardiomyopathies requiring more monitoring for less atrial fibrillation-related complications: a clustering analysis based on the French registry on hypertrophic cardiomyopathy (REMY)

Author: Gilbert Habib, P. Reant, Mariana Mirabel, Olivier Huttin, Marion Hourqueig, Fabien Labombarda, Thibaud Damy, Philippe Charron, Albert Hagège, Erwan Donal, Jean-Christophe Eicher, Guillaume Bouzillé, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], GHU AP-HP Centre Université de Paris, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Henri Mondor, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance Publique - Hôpitaux de Marseille (APHM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, 0302 clinical medicine, Mitral valve, Atrial Fibrillation, Cluster Analysis, 030212 general & internal medicine, Prospective Studies, Registries, Stroke, education.field_of_study, Hypertrophic cardiomyopathy, Atrial fibrillation, General Medicine, Middle Aged, Prognosis, 3. Good health, Hospitalization, medicine.anatomical_structure, Echocardiography, Cardiology, cardiovascular system, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, France, Abnormality, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Population, Diastole, Risk Assessment, Clustering, 03 medical and health sciences, Internal medicine, medicine.artery, medicine, Humans, cardiovascular diseases, education, Aged, Retrospective Studies, business.industry, Bayes Theorem, Cardiomyopathy, Hypertrophic, medicine.disease, Heart Disease Risk Factors, Pulmonary artery, business, Follow-Up Studies
Abstract: International audience; AIMS: Defining the risk of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients is an important clinical and prognostic challenge. The aim of this study is to determine HCM phenogroups with different risk of AF occurrence at 5 years. METHODS AND RESULTS: We applied retrospectively the Bayesian method, which can analyze a large number of variables, to differentiate phenogroups of patients with different risks of AF and prognoses across a French prospective on-going hospital-based registry of adult HCM patients (REMY). Clinical and imaging data were prospectively recorded, and patients were followed for 5 years. A total of 1431 HCM patients were recruited, including 1275 analyzed in the present study after exclusion criteria. The population included 412 women, 369 patients with obstructive HCM, and 252 implanted with an ICD. AF occurred in 167 (11.6%) patients during the 5 year follow-up. Three phenogroups were defined according to their common clinical and echocardiographic characteristics. Patients at the highest risk were oldest, more often female, with more frequent comorbidities, anteroposterior diameter of the left atrium was significantly greater, with diastolic dysfunction, outflow-tract obstruction, and mitral valve abnormality, and presented higher pulmonary artery pressure and/or right-ventricular dysfunction. These also had a higher risk of all-cause hospitalizations and death. CONCLUSION: Based on a clustering analysis, three phenogroups of HCM according to the risk of AF occurrence can be identified. It can indicate which patients should be more monitored and/or treated, particular to prevent the risk of stroke.
Published: 2020
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19. Comparison Between ESC and Duke Criteria for the Diagnosis of Prosthetic Valve Infective Endocarditis

Author: Mainardi, Jean-Luc, Fernandez-Gerlinger, Marie-Paule, Hagège, Albert, Casalta, Anne Claire, Casalta, Jean Paul, Philip, Mary, Tessonier, Laetitia, Mancini, Julien, Mainardi, Jl, Fernandez-Gerlinger, MP, Lussato, David, Attias, David, Cammilleri, Serge, Weinmann, Pierre, Hagege, A, Arregle, Florent, Martel, Hélène, Oliver, Leopold, Camoin, Laurence, Casalta, AC, Casalta, JP, Gouriet, Frederique, Riberi, Alberto, Lepidi, Hubert, Raoult, Didier, Drancourt, Michel, Habib, Gilbert, Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de médecine nucléaire [Marseille], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre cardiologique du Nord (CCN), Médecine nucléaire [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Guedj, Eric, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire de Recherche Moléculaire sur les Antibiotiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de microbiologie, Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Institut universitaire de formation des maîtres - Nord-Pas-de-Calais (IUFM Nord-Pas-de-Calais), Université d'Artois (UA), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), and INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Cardiology, 030204 cardiovascular system & hematology, valve disease, Duke criteria, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Fluorodeoxyglucose F18, Predictive Value of Tests, Positron Emission Tomography Computed Tomography, medicine, Endocarditis, Humans, Radiology, Nuclear Medicine and imaging, guidelines, ComputingMilieux_MISCELLANEOUS, Prosthetic valve, nuclear imaging, Reproducibility, medicine.diagnostic_test, business.industry, Reproducibility of Results, medicine.disease, Confidence interval, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Positron emission tomography, Infective endocarditis, Heart Valve Prosthesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Radiopharmaceuticals, Cardiology and Cardiovascular Medicine, Nuclear medicine, business, Kappa, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives: The primary objective was to assess the value of the European Society of Cardiology (ESC) criteria, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in prosthetic valve infective endocarditis (PVE). Secondary objectives were: 1) to assess the reproducibility of 18F-FDG-PET/CT; 2) to compare its diagnostic value with that of echocardiography; and 3) to assess the diagnostic value of the presence of a diffuse splenic uptake BACKGROUND: 18F-FDG PET/CT has been added as a major criterion in the ESC 2015 infective endocarditis (IE) guidelines, but the benefit of the ESC criteria has not been prospectively compared with the conventional Duke criteria.Methods: Between 2014 and 2017, 175 patients with suspected PVE were prospectively included in 3 French centers. After exclusion of patients with uninterpretable 18F-FDG PET/CT, 115 patients were evaluated, including 91 definite and 24 rejected IE, as defined by an expert consensus.Results: Cardiac uptake by 18F-FDG PET/CT was observed in 67 of 91 patients with definite PVE and 6 with rejected IE (sensitivity 73.6% [95% confidence interval (CI): 63.3% to 82.3%], specificity 75% [95% CI: 53.3% to 90.2%]). The ESC 2015 classification increased the sensitivity of Duke criteria from 57.1% (95% CI: 46.3% to 67.5%) to 83.5% (95% CI: 74.3% to 90.5%) (p < 0.001), but decreased its specificity from 95.8% (95% CI: 78.9% to 99.9%) to 70.8% (95% CI: 48.9% to 87.4%). Intraobserver reproducibility of 18F-FDG PET/CT was good (kappa = 0.84) but interobserver reproducibility was less satisfactory (kappa = 0.63). A diffuse splenic uptake was observed in 24 (20.3%) patients, including 23 (25.3%) of definite PVE, and only 1 (4.2%) rejected PVE (p = 0.024).Conclusions: 18F-FDG PET/CT is a useful diagnostic tool in suspected PVE, and explains the greater sensitivity of ESC criteria than Duke criteria. However, 18F-FDG PET/CT also presents with important limitations concerning its feasibility, specificity, and reproducibility. Our study describes for the first time a new endocarditis criterion, that is, the presence of a diffuse splenic uptake on 18F-FDG PET/CT.
Published: 2020
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20. Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progenitors

Author: Solenne Paiva, Nadia El Harane, Jean-Sébastien Silvestre, Yeranuhi Hovhannisyan, Camille Brunaud, Léa Thiebault, Jeanne Gauthier, Onnik Agbulut, Marc P. Renault, Philippe Menasché, Hany J Neametalla, Marie-Cécile Perier, Nicolas Cagnard, Albert Hagège, Mathilde Lemitre, Bruna Lima Correa, Valérie Bellamy, Angéline Duché, Anaïs Kervadec, Alexandra T Bourdillon, Nisa Renault, Laetitia Pidial, and Alexandre R. Colas
Subjects: Pluripotent Stem Cells, 0301 basic medicine, Cell Survival, Cell, Myocardial Infarction, Mice, Nude, Pharmacology, Extracellular Vesicles, 03 medical and health sciences, Basic Science, Animals, Humans, Myocyte, Medicine, Myocytes, Cardiac, Progenitor cell, Induced pluripotent stem cell, Embryonic Stem Cells, Cell Proliferation, Heart Failure, Tube formation, business.industry, Cell growth, Embryonic stem cell, Endothelial stem cell, MicroRNAs, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, Cardiology and Cardiovascular Medicine, business
Abstract: Aims We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. Methods and results The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy. In vitro bioactivity assays were used to evaluate their cellular effects. Cell and EV microRNA (miRNA) content were assessed by miRNA array. Myocardial infarction was induced in 199 nude mice. Three weeks later, mice with left ventricular ejection fraction (LVEF) ≤ 45% received transcutaneous echo-guided injections of iPSC-CM (1.4 × 106, n = 19), iPSC-Pg (1.4 × 106, n = 17), total EV secreted by 1.4 × 106 iPSC-Pg (n = 19), or phosphate-buffered saline (control, n = 17) into the peri-infarct myocardium. Seven weeks later, hearts were evaluated by echocardiography, histology, and gene expression profiling, blinded to treatment group. In vitro, EV were internalized by target cells, increased cell survival, cell proliferation, and endothelial cell migration in a dose-dependent manner and stimulated tube formation. Extracellular vesicles were rich in miRNAs and most of the 16 highly abundant, evolutionarily conserved miRNAs are associated with tissue-repair pathways. In vivo, EV outperformed cell injections, significantly improving cardiac function through decreased left ventricular volumes (left ventricular end systolic volume: -11%, P
Published: 2018
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21. Transplantation of Human Embryonic Stem Cell–Derived Cardiovascular Progenitors for Severe Ischemic Left Ventricular Dysfunction

Author: Alexandre Parouchev, Bernard Cholley, Isabelle Cacciapuoti, Philippe Menasché, Valérie Vanneaux, Nadine Benhamouda, Valérie Bellamy, Hélène Blons, Jean-Hugues Trouvin, Eric Tartour, Michel Desnos, Jean-Roch Fabreguettes, Albert Hagège, Reem Al-Daccak, Gérard Tachdjian, Onnik Agbulut, Alain Bel, Lucie Tosca, Dominique Charron, and Jérôme Larghero
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Human Embryonic Stem Cells, Population, Myocardial Ischemia, Cohort Studies, Ventricular Dysfunction, Left, 03 medical and health sciences, Interquartile range, Internal medicine, Clinical endpoint, Humans, Medicine, Coronary Artery Bypass, Progenitor cell, education, Aged, education.field_of_study, Ejection fraction, business.industry, Middle Aged, medicine.disease, Survival Rate, Transplantation, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, Heart failure, Cardiology, Feasibility Studies, Female, Cardiology and Cardiovascular Medicine, business, Stem Cell Transplantation, Artery
Abstract: Background In addition to scalability, human embryonic stem cells (hESCs) have the unique advantage of allowing their directed differentiation toward lineage-specific cells. Objectives This study tested the feasibility of leveraging the properties of hESCs to generate clinical-grade cardiovascular progenitor cells and assessed their safety in patients with severe ischemic left ventricular dysfunction. Methods Six patients (median age 66.5 years [interquartile range (IQR): 60.5 to 74.7 years]; median left ventricular ejection fraction 26% [IQR: 22% to 32%]) received a median dose of 8.2 million (IQR: 5 to 10 million) hESC-derived cardiovascular progenitors embedded in a fibrin patch that was epicardially delivered during a coronary artery bypass procedure. The primary endpoint was safety at 1 year and focused on: 1) cardiac or off-target tumor, assessed by imaging (computed tomography and fluorine-18 fluorodeoxyglucose positron emission tomography scans); 2) arrhythmias, detected by serial interrogations of the cardioverter-defibrillators implanted in all patients; and 3) alloimmunization, assessed by the presence of donor-specific antibodies. Patients were followed up for a median of 18 months. Results The protocol generated a highly purified (median 97.5% [IQR: 95.5% to 98.7%]) population of cardiovascular progenitors. One patient died early post-operatively from treatment-unrelated comorbidities. All others had uneventful recoveries. No tumor was detected during follow-up, and none of the patients presented with arrhythmias. Three patients developed clinically silent alloimmunization. All patients were symptomatically improved with an increased systolic motion of the cell-treated segments. One patient died of heart failure after 22 months. Conclusions This trial demonstrates the technical feasibility of producing clinical-grade hESC-derived cardiovascular progenitors and supports their short- and medium-term safety, thereby setting the grounds for adequately powered efficacy studies. (Transplantation of Human Embryonic Stem Cell-derived Progenitors in Severe Heart Failure [ESCORT]; NCT02057900)
Published: 2018
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22. Head-to-head comparison of the diagnostic performance of coronary computed tomography angiography and dobutamine-stress echocardiography in the evaluation of acute chest pain with normal ECG findings and negative troponin tests: A prospective multicenter study

Author: Jean-Nicolas Dacher, Ralph Niarra, Arshid Azarine, Elie Mousseaux, Hélène Eltchaninoff, B. Dubourg, Gilles Chatellier, Mourad Bensalah, Benoit Diebold, Ludivine Perdrix, Yannick Jobic, Fabrice Bauer, Nicolas Mansencal, Eric Durand, Albert Hagège, J. Caudron, and Martine Gilard
Subjects: Male, Chest Pain, medicine.medical_specialty, Acute coronary syndrome, Computed Tomography Angiography, 030204 cardiovascular system & hematology, Chest pain, Likelihood ratios in diagnostic testing, Coronary artery disease, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, Dobutamine, Internal medicine, medicine, Humans, Single-Blind Method, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, biology, business.industry, Middle Aged, medicine.disease, Troponin, Multicenter study, Ecg findings, biology.protein, Cardiology, Female, Radiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Echocardiography, Stress, Follow-Up Studies
Abstract: Objective To perform a head-to-head comparison of coronary CT angiography (CCTA) and dobutamine-stress echocardiography (DSE) in patients presenting recent chest pain when troponin and ECG are negative. Methods Two hundred seventeen patients with recent chest pain, normal ECG findings, and negative troponin were prospectively included in this multicenter study and were scheduled for CCTA and DSE. Invasive coronary angiography (ICA), was performed in patients when either DSE or CCTA was considered positive or when both were non-contributive or in case of recurrent chest pain during 6month follow-up. The presence of coronary artery stenosis was defined as a luminal obstruction >50% diameter in any coronary segment at ICA. Results ICA was performed in 75 (34.6%) patients. Coronary artery stenosis was identified in 37 (17%) patients. For CCTA, the sensitivity was 96.9% (95% CI 83.4–99.9), specificity 48.3% (29.4–67.5), positive likelihood ratio 2.06 (95% CI 1.36–3.11), and negative likelihood ratio 0.07 (95% CI 0.01–0.52). The sensitivity of DSE was 51.6% (95% CI 33.1–69.9), specificity 46.7% (28.3–65.7), positive likelihood ratio 1.03 (95% CI 0.62–1.72), and negative likelihood ratio 1.10 (95% CI 0.63–1.93). The CCTA: DSE ratio of true-positive and false-positive rates was 1.70 (95% CI 1.65–1.75) and 1.00 (95% CI 0.91–1.09), respectively, when non-contributive CCTA and DSE were both considered positive. Only one missed acute coronary syndrome was observed at six months. Conclusions CCTA has higher diagnostic performance than DSE in the evaluation of patients with recent chest pain, normal ECG findings, and negative troponine to exclude coronary artery disease.
Published: 2017
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23. An expert consensus document on the management of cardiovascular manifestations of Fabry disease

Author: Dominique P. Germain, Aris Anastasakis, Iacopo Olivotto, Aleš Linhart, Perry M. Elliott, Maurizio Pieroni, Franco Cecchi, Albert Hagège, Juan R. Gimeno, Derralynn Hughes, Giuseppe Limongelli, Mohammed M Akhtar, Mehdi Namdar, Linhart, A., Germain, D. P., Olivotto, I., Akhtar, M. M., Anastasakis, A., Hughes, D., Namdar, M., Pieroni, M., Hagege, A., Cecchi, F., Gimeno, J. R., Limongelli, G., and Elliott, P.
Subjects: Consensus, Heart disease, Cardiomyopathy, Globotriaosylceramide, 030204 cardiovascular system & hematology, Bioinformatics, Sudden cardiac death, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, medicine, Humans, GLA gene, ddc:616, Heart Failure, Fabry disease, business.industry, Enzyme replacement therapy, medicine.disease, chemistry, Heart failure, alpha-Galactosidase, cardiovascular system, Cardiology and Cardiovascular Medicine, business
Abstract: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the α-galactosidase A (GLA) gene that leads to reduced or undetectable α-galactosidase A enzyme activity and progressive accumulation of globotriaosylceramide and its deacylated form globotriaosylsphingosine in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD-related heart disease and expert consensus recommendations for its management.
Published: 2020

24. Prognostic value of the 12-lead surface electrocardiogram in sarcomeric hypertrophic cardiomyopathy: data from the REMY French register

Author: Patricia Reant, Vincent Auffret, Albert Hagège, Tania Puscas, Philippe Ritter, Philippe Mabo, Erwan Donal, Mariana Mirabel, Dominique Fargeau, Xavier Jeunemaitre, Claude Daubert, Louis Larnier, Amélie Reynaud, Eloi Marijon, Stephane Lafitte, Nicolas Ledieu, Coralie Marie, CHU Pontchaillou [Rennes], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Sanofi Genzyme, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Sarcomeres, medicine.medical_specialty, Registry, Risk predictors, 030204 cardiovascular system & hematology, 03 medical and health sciences, QRS complex, Electrocardiography, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Physiology (medical), Internal medicine, T wave, Clinical endpoint, Medicine, Humans, 030212 general & internal medicine, cardiovascular diseases, Retrospective Studies, Heart Failure, business.industry, Surrogate endpoint, Hazard ratio, Hypertrophic cardiomyopathy, Retrospective cohort study, 12-lead electrocardiogram, Right bundle branch block, Cardiomyopathy, Hypertrophic, medicine.disease, Prognosis, 3. Good health, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: Aims To identify independent electrocardiogram (ECG) predictors of long-term clinical outcome based on standardized analysis of the surface ECG in a large multicentre cohort of patients with sarcomeric hypertrophic cardiomyopathy (HCM). Methods and results Retrospective observational study from the REMY French HCM clinical research observatory. Primary endpoint was a composite of all-cause mortality, major non-fatal arrhythmic events, hospitalization for heart failure (HF), and stroke. Secondary endpoints were components of the primary endpoint. Uni- and multivariable Cox proportional hazard regression analysis was performed to identify independent predictors. Among 994 patients with HCM, only 1.8% had a strictly normal baseline ECG. The most prevalent abnormalities were inverted T waves (63.7%), P-wave abnormalities (30.4%), and abnormal Q waves (25.5%). During a mean follow-up of 4.0 ± 2.0 years, a total of 272 major cardiovascular events occurred in 217 patients (21.8%): death or heart transplant in 98 (9.8%), major arrhythmic events in 40 (4.0%), HF hospitalization in 115 (11.6%), and stroke in 23 (2.3%). At multivariable analysis using ECG covariates, prolonged QTc interval, low QRS voltage, and PVCs of right bundle branch block pattern predicted worse outcome, but none remained independently associated with the primary endpoint after adjustment on main demographic and clinical variables. For secondary endpoints, abnormal Q waves independently predicted all-cause death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.23–4.47; P = 0.009] and prolonged QTc the risk of HF hospitalization (HR 1.006, 95% CI 1.001–1.011; P = 0.024). Conclusion The 12-lead surface ECG has no independent value to predict the primary outcome measure in patients with HCM. The 12-lead surface ECG has been widely used as a screening tool in HCM but its prognostic value remains poorly known. The value of baseline surface ECG to predict long-term clinical outcomes was studied in a cohort of 994 patients with sarcomeric HCM. The surface ECG has no significant additional value to predict outcome in this patient population
Published: 2020
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25. Remission and Low Disease Activity in Psoriatic Arthritis Publications: A Systematic Literature Review with Meta-Analysis

Author: M. Gayraud, Benjamin Hagège, Stéphane Mitrovic, Elina Tan, Laure Gossec, Bruno Fautrel, Gestionnaire, HAL Sorbonne Université 5, Institut Mutualiste de Montsouris (IMM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Severity of Illness Index, law.invention, Disease activity, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Treatment targets, Rheumatology, Randomized controlled trial, law, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, 030203 arthritis & rheumatology, business.industry, Arthritis, Psoriatic, Remission Induction, medicine.disease, [SDV] Life Sciences [q-bio], Prostate-specific antigen, Treatment Outcome, Systematic review, Antirheumatic Agents, Meta-analysis, Outcomes research, business
Abstract: Objectives Remission (REM) or low disease activity (LDA) is the treatment target in psoriatic arthritis (PsA). The objective of this study was to assess the reporting and prevalence of REM/LDA in published studies of PsA. Methods This was a systematic literature review of all clinical papers published in PubMed, EMBASE or Cochrane database in English between 2012 and 2019 in the field of PsA. Data were collected regarding reporting of REM/LDA by very low disease activity/minimal disease activity (VLDA/MDA), Disease Activity index for Psoriatic Arthritis (DAPSA), or Disease Activity Score 28 joints (DAS28). The pooled rates of REM and LDA by each definition were calculated by random effect meta-analysis. Results In all, 258 publications (corresponding to 114 651 patients), of which 81 (31%) were randomized controlled trials, were analysed: patients’ mean age was 49.4 ( 4.4) years; with a mean disease duration of 8.5 ( 3.8) years. REM/LDA was reported in 91/258 (35.3%) publications. VLDA/MDA was used in 61/91 (67.0%) studies, DAPSA in 27/91 (29.6%) and DAS28 in 28/91 (30.7%), with 40/91 (43.9%) papers reporting several of these definitions. The pooled prevalence (lower–upper limits) of REM was 13.1% (10.9–15.4), 23.1% (16.8–30.1) and 42.1% (33.9–50.4) using VLDA, DAPSA-REM and DAS28, respectively. For LDA the pooled prevalence was 36.3% (32.3–40.5), 52.8% (41.8–63.6) and 60.4% (52.5–68.0) using MDA, DAPSA-LDA and DAS28, respectively. Conclusion REM/LDA status was reported in only1/3 of recent studies on PsA, with important variations in the frequency of these outcomes according to the definition used: 13.1–42.1% for REM, and 36.3–60.4% for LDA. This highlights the need for consensus.
Published: 2020
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26. Treatment needs and expectations for Fabry disease in France: development of a new Patient Needs Questionnaire

Author: Esther Noel, Najya Bedreddine, Albert Hagège, Soumeya Bekri, Delphine Genevaz, Didier Lacombe, Alain Fouilhoux, Olivier Lidove, Pierre Ronco, Bertrand Dussol, Valérie Derrien Ansquer, Dominique P. Germain, Frédérique Dupuis-Siméon, CHU Strasbourg, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Psychometrics, Best practice, Population, Patient self-reported tool, lcsh:Medicine, Disease, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Patient Needs Questionnaire, education, Psychometric analysis, Genetics (clinical), Reliability (statistics), National health, education.field_of_study, Fabry disease, business.industry, Research, 030503 health policy & services, lcsh:R, Lysosomal disorders, General Medicine, Patient-reported outcome measure, medicine.disease, Disease Presentation, Family medicine, Patient association, Quality of Life, France, 0305 other medical science, business
Abstract: Background Fabry disease (FD) is a rare, X-linked, inherited lysosomal disease caused by absent or reduced α-galactosidase A activity. Due to the heterogeneity of disease presentation and progression, generic patient-reported outcome (PRO) tools do not provide accurate insight into patients’ daily lives and impact of disease specific treatments. Also, the French National Health Authority, (HAS) actively encourages a patient-centric approach to improve the quality of care throughout the patient journey. In response to this initiative, we aimed to develop and validate a specific, self-reported, Patient Needs Questionnaire for people living with Fabry disease to appraise patient needs and expectations towards their treatment (PNQ Fabry). This endeavour was led with the help of French patient associations (APMF & VML) and dedicated expert centres. PNQ Fabry was developed according to the FDA/EMA methodologies and best practices for the development of PRO tools in rare diseases. Our approach comprised of three steps, as follows: concept elicitation and item generation, item reduction, and final validation of the questionnaire through a two-stage survey. Results Intrinsic and extrinsic reliability was established, using a validated benchmark questionnaire. With the invaluable help of patient associations, we recruited a satisfactory population in this rare disease setting, to ensure robust participation to validate our PNQ (final number of questionnaires: 76). At the end of the process, a 26-item patient-reported questionnaire was obtained with excellent psychometric properties, exhibiting very satisfactory measurement outcomes for reliability and validity. The results of this initiative demonstrate that the PNQ Fabry is accurate, suitable and tailored to FD patients, as it addresses themes identified during patient interviews, that were further validated through statistical analyses of quantitative surveys. An ongoing phase IV study is using this tool. Conclusion We believe the PNQ Fabry will be a reliable and insightful tool in clinical practice, to improve patient management in FD.
Published: 2019
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27. Genome-Wide Association Study-Driven Gene-Set Analyses, Genetic, and Functional Follow-Up Suggest GLIS1 as a Susceptibility Gene for Mitral Valve Prolapse

Author: Adrien Georges, Susan A. Slaugenhaupt, Patrick T. Ellinor, Jean-Jacques Schott, Jorge Solis, David J. Milan, Nabila Bouatia-Naji, Albert Hagège, Katelyn Toomer, Robert A. Levine, Nathan R. Tucker, Russell A. Norris, Xavier Jeunemaitre, Leticia Fernández-Friera, Francesca N. Delling, Sergiy Kyryachenko, Christian Dina, and Mengyao Yu
Subjects: 0301 basic medicine, Male, Actin filament organization, Genome-wide association study, 030204 cardiovascular system & hematology, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Mitral valve, medicine, Mitral valve prolapse, Animals, Humans, Genetic Predisposition to Disease, Heart valve, Zebrafish, Zinc finger, Mitral regurgitation, Mitral Valve Prolapse, Mitral Valve Insufficiency, Heart, General Medicine, medicine.disease, biology.organism_classification, Heart Valves, United Kingdom, DNA-Binding Proteins, 030104 developmental biology, medicine.anatomical_structure, Female, Follow-Up Studies, Genome-Wide Association Study, Transcription Factors
Abstract: Background Mitral valve prolapse (MVP) is a common heart valve disease, the most frequent indication for valve repair or replacement. MVP is characterized by excess extracellular matrix secretion and cellular disorganization, which leads to bulky valves that are unable to coapt correctly during ventricular systole resulting in mitral regurgitation, and it is associated with sudden cardiac death. Here we aim to characterize globally the biological mechanisms underlying genetic susceptibility to MVP to better characterize its triggering mechanisms. Methods We applied i -GSEA4GWAS and DEPICT, two pathway enrichment tools to MVP genome-wide association studies. We followed-up the association with MVP in an independent dataset of cases and controls. This research was conducted using the UK Biobank Resource. Immunohistochemistry staining for Glis1 (GLIS family zinc finger 1) was conducted in developing heart of mice. Knockdown of Glis1 using morpholinos was performed in zebrafish animals 72 hours postfertilization. Results We show that genes at risk loci are involved in biological functions relevant to actin filament organization, cytoskeleton biology, and cardiac development. The enrichment for positive regulation of transcription, cell proliferation, and migration motivated the follow-up of GLIS1 , a transcription factor from the Krüppel-like zinc finger family. In combination with previously available data, we now report a genome-wide significant association with MVP (odds ratio, 1.20; P =4.36×10 -10 ), indicating that Glis1 is expressed during embryonic development predominantly in nuclei of endothelial and interstitial cells of mitral valves in mouse. We also show that Glis1 knockdown causes atrioventricular regurgitation in developing hearts in zebrafish. Conclusions Our findings define globally molecular and cellular mechanisms underlying common genetic susceptibility to MVP and implicate established and unprecedented mechanisms. Through the GLIS1 association and function, we point at regulatory functions during cardiac development as common mechanisms to mitral valve degeneration.
Published: 2019

28. Primary cilia defects causing mitral valve prolapse

Author: Kelsey Moore, Russell A. Norris, Francesca N. Delling, Reece Moore, Ka’la D. Drayton, Roger R. Markwald, Peter Kohl, Willian A. da Silveira, Simon C. Body, Neal Peterson, Solena Le Scouarnec, Janiece Glover, Eva A. Rog-Zielinska, E. Starr Hazard, Katelynn Toomer, Susan A. Slaugenhaupt, Jean-Jacques Schott, David J. Milan, Breiona J. Catching, Ronen Durst, Alex Drohan, Lilong Guo, Federica del Monte, Harrison Brand, Patrick T. Ellinor, Nabila Bouatia-Naji, Thierry Le Tourneau, Diana Fulmer, Joshua H. Lipschutz, Xavier Jeunemaitre, Albert Hagège, Rupak Mukherjee, Christian Dina, Baolin Wang, Ryan L. Collins, Rebecca Stairley, Mengyao Yu, Robert A. Levine, Michael E. Talkowski, Sandra Ramos-Ortiz, Maire Leyne, Alexander Awgulewitsch, Andy Wessels, and Gary Hardiman
Subjects: Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Time Factors, Genome-wide association study, 030204 cardiovascular system & hematology, Myxomatous degeneration, Article, Sudden cardiac death, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Ciliogenesis, Mitral valve, Morphogenesis, medicine, Animals, Humans, Mitral valve prolapse, Missense mutation, cardiovascular diseases, Cilia, Adaptor Proteins, Signal Transducing, Mice, Knockout, Mitral Valve Prolapse, Base Sequence, business.industry, Tumor Suppressor Proteins, Cilium, Mitral Valve Insufficiency, General Medicine, medicine.disease, Heart Valves, Extracellular Matrix, Pedigree, 030104 developmental biology, medicine.anatomical_structure, Echocardiography, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Genome-Wide Association Study
Abstract: Mitral valve prolapse (MVP) affects 1 in 40 people and is the most common indication for mitral valve surgery. MVP can cause arrhythmias, heart failure, and sudden cardiac death, and to date, the causes of this disease are poorly understood. We now demonstrate that defects in primary cilia genes and their regulated pathways can cause MVP in familial and sporadic nonsyndromic MVP cases. Our expression studies and genetic ablation experiments confirmed a role for primary cilia in regulating ECM deposition during cardiac development. Loss of primary cilia during development resulted in progressive myxomatous degeneration and profound mitral valve pathology in the adult setting. Analysis of a large family with inherited, autosomal dominant nonsyndromic MVP identified a deleterious missense mutation in a cilia gene, DZIP1 A mouse model harboring this variant confirmed the pathogenicity of this mutation and revealed impaired ciliogenesis during development, which progressed to adult myxomatous valve disease and functional MVP. Relevance of primary cilia in common forms of MVP was tested using pathway enrichment in a large population of patients with MVP and controls from previously generated genome-wide association studies (GWAS), which confirmed the involvement of primary cilia genes in MVP. Together, our studies establish a developmental basis for MVP through altered cilia-dependent regulation of ECM and suggest that defects in primary cilia genes can be causative to disease phenotype in some patients with MVP.
Published: 2019
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29. Inclusion of Older Patients with Cancer in Clinical Trials: The SAGE Prospective Multicenter Cohort Survey

Author: Simon Pernot, Christophe Tournigand, Isabelle Baumgaertner, Florent Dayde, Olivier Dubreuil, Thomas Aparicio, Astrid Lièvre, Florence Canoui-Poitrine, Romain Coriat, Francesco Brunetti, Elena Paillaud, Meoïn Hagège, Sylvie Bastuji-Garin, Karin Maley, Daniel Lopez-Trabada-Ataz, IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pontchaillou [Rennes], Ecologie fonctionnelle et biogéochimie des sols et des agro-écosystèmes (UMR Eco&Sols), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Association des Gastroentérologues Oncologues [Paris] (AGEO), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], CHU Pitié-Salpêtrière [AP-HP], Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Inserm U1016, Paris Descartes University, Hôpital Diaconesses-Croix-Saint-Simon, Paris, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Réseau National Alimentation Cancer Recherche (réseau NACRe)
Subjects: Male, Cancer Research, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Randomized controlled trial, law, Internal medicine, Neoplasms, Surveys and Questionnaires, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Aged, Eligibility, Inclusion, Clinical Trials as Topic, business.industry, Over 80s, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Colorectal cancer, Confidence interval, Clinical trial, Geriatric Oncology, Oncology, 030220 oncology & carcinogenesis, Relative risk, Cohort, Quality of Life, Observational study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, business
Abstract: Background The primary objective was to evaluate the rates of older patients with colorectal cancer (CRC) who were eligible for a clinical trial, invited to participate, and, ultimately, included. The secondary objective was to assess the reasons for ineligibility, noninvitation, and noninclusion and factors associated. Materials and Methods The Sujets AGés dans les Essais Cliniques (SAGE; Older Subjects in Clinical Trials) multicenter prospective cohort was established in seven centers (10 departments of medical oncology, digestive oncology, and digestive surgery) between 2012 and 2016. All patients with CRC aged 65 or older were studied. The endpoints were clinical trial availability, patient's eligibility, invitation, and enrollment in a trial. Results We included 577 older patients (mean age ± SD: 75.6 ± 7 years; males: 56%; metastasis: 41%). Thirty-seven trials were ongoing (one trial for older patients). Of the 474 patients with at least one available trial for their cancer stage and site, 127 (27%) were eligible; 84 of these 127 (66%) were invited to participate, and 70 of these 84 (83%) were included. In a multivariate analysis, noninvitation was found to be associated with older age (p = .016): adjusted relative risk (95% confidence interval), 0.14 (0.02–0.60) for ≥80 vs. 65–69; 0.54 (0.18-1.04) for 75–79 vs. 65–69; 0.47 (0.17-0.93) for 70–74 vs. 65–69. Conclusion Three-quarters of older patients with CRC were ineligible for a clinical trial. One-third of the eligible patients were not invited to participate in a trial, and 17% of invited patients were not included. Few trials are reserved for older patients. Patients aged 80 or older were significantly less likely to be eligible for a trial and invited to participate. Clinical trial identification number: NCT01754636. Implications for Practice The results of this study suggest that barriers to participation of older patients in clinical trials are particularly marked at age 80 years or older. Secondly, the results emphasize the need for trials for older patients. Thirdly, there is also a need for more pragmatic “real-world” trials, rather than solely randomized trials performed in idealized settings with strictly selected patients. Large prospective observational cohorts with a precise follow-up of toxicity, functional decline, and quality of life may constitute one way of generating more data on the risk-benefit ratio for cancer treatments in older patients.
Published: 2019
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30. Deployment dynamics of hypnotic anger modulation

Author: Jérôme Sackur, Hernán Anlló, and Joshua Hagège
Subjects: Hypnosis, Salience (language), medicine.drug_class, media_common.quotation_subject, Emotions, Experimental and Cognitive Psychology, Cognition, Anger, Attentional Blink, Hypnotic, Arts and Humanities (miscellaneous), Response strategy, Dynamics (music), Developmental and Educational Psychology, medicine, Humans, Hypnotics and Sedatives, Attention, Attentional blink, Suggestion, Psychology, Cognitive psychology, media_common
Abstract: To understand the role that attention plays in the deployment timeline of hypnotic anger modulation, we composed an Attentional Blink paradigm where the first and second targets were faces, expressing neutral or angry emotions. We then suppressed the salience of angry faces through a “hypnotic numbing” suggestion. We found that hypnotic suggestion only attenuated the emotional salience of the second target (T2). By implementing drift-diffusion decision modelling, we also found that hypnotic suggestion mainly affected decision thresholds. These findings suggest that hypnotic numbing resulted from belated changes in response strategy. Interestingly, a contrast against non-hypnotized participants revealed that the numbing suggestion had the instruction-like feature of incorporating emotional valence into the attentional task-set. Together, our results portray hypnotic anger modulation as a two-tiered process: first, hypnotic suggestion alters the attentional task-set; second, provided processing and response preparation are not interrupted, a hypnotizability-dependent response based on said altered task-set is produced through late cognitive control strategies.
Published: 2021
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31. Anticoagulants oraux directs et insuffisance cardiaque

Author: Rémi Sabatier, Michel Galinier, Jean-Noël Trochu, Erwan Donal, P. Jourdain, Ariel Cohen, Christophe Leclercq, Fabrice Bauer, Albert Hagège, Alain Cohen-Solal, Richard Isnard, Thibaud Damy, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Nouvelles Cibles Pharmacologiques de la Protection Endothéliale et de l'Insuffisance Cardiaque (EnVI), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Unité de recherche de l'institut du thorax (ITX-lab)
Subjects: medicine.medical_specialty, Vitamin K, medicine.drug_class, Population, Administration, Oral, 030204 cardiovascular system & hematology, Dabigatran, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Edoxaban, Thromboembolism, Internal medicine, medicine, Humans, Vitamin K antagonits, 030212 general & internal medicine, education, Heart Failure, Rivaroxaban, education.field_of_study, business.industry, Non-vitamin K antagonists oral anticoagulants, Warfarin, Anticoagulants, Atrial fibrillation, General Medicine, Vitamin K antagonist, medicine.disease, 3. Good health, chemistry, Heart failure stroke, Cardiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Apixaban, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: National audience; Thromboembolism contributes to morbidity and mortality in patients with heart failure (HF), and atrial fibrillation (AF) is one of the main factors promoting this complication. As they share many risk factors, HF and AF frequently coexist, and patients with both conditions are at a particularly high risk of thromboembolism. Non-vitamin K antagonist oral anticoagulants (NOACs) are direct antagonists of thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban and edoxaban), and were designed to overcome the limitations of vitamin K antagonists. Compared with warfarin in non-valvular AF, NOACs demonstrated non-inferiority with better safety, most particularly for intracranial haemorrhages. Therefore, the European Society of Cardiology guidelines recommend NOACs for most patients with non-valvular AF. Subgroups of patients with both AF and HF from the pivotal studies investigating the safety and efficacy of NOACs have been analysed and, for each NOAC, results were similar to those of the total analysis population. A recent meta-analysis of these subgroups has confirmed the better efficacy and safety of NOACs in patients with AF and HF – particularly the 41% decrease in the incidence of intracranial haemorrhages. The prothrombotic state associated with HF suggests that patients with HF in sinus rhythm could also benefit from treatment with NOACs. However, in the absence of clinical trial data supporting this indication, current guidelines do not recommend anticoagulant treatment of patients with HF in sinus rhythm. In conclusion, recent analyses of pivotal studies support the use of NOACs in accordance with their indications in HF patients with non-valvular AF. © 2016 Elsevier Masson SAS
Published: 2016
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32. Cardiovascular progenitor–derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure

Author: Min Yin, Valérie Vanneaux, Albert Hagège, Nadia El Harane, Jean-Sébastien Silvestre, Adèle Richart, Chantal M. Boulanger, Hany Nemetalla, Anaïs Kervadec, Marie Cécile Perier, Jérôme Larghero, Hadi Toeg, Marc Ruel, Nisa Renault, Valérie Bellamy, Mathilde Lemitre, Xavier Loyer, Isabelle Cacciapuoti, Philippe Menasché, and Lousineh Arakelian
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Cardiac function curve, Pathology, medicine.medical_specialty, Myocardial Infarction, 030204 cardiovascular system & hematology, Pharmacology, Cell therapy, Extracellular Vesicles, Mice, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, Fibrosis, medicine, Animals, Humans, Myocytes, Cardiac, Myocardial infarction, Progenitor cell, Embryonic Stem Cells, Heart Failure, Transplantation, business.industry, Myocardium, medicine.disease, Coronary arteries, 030104 developmental biology, medicine.anatomical_structure, Heart failure, Chronic Disease, Surgery, Cardiology and Cardiovascular Medicine, business
Abstract: Background Cell-based therapies are being explored as a therapeutic option for patients with chronic heart failure following myocardial infarction. Extracellular vesicles (EV), including exosomes and microparticles, secreted by transplanted cells may orchestrate their paracrine therapeutic effects. We assessed whether post-infarction administration of EV released by human embryonic stem cell–derived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways. Methods Mice underwent surgical occlusion of their left coronary arteries. After 2–3 weeks, 95 mice included in the study were treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM; vehicle control) delivered by percutaneous injections under echocardiographic guidance into the peri-infarct myocardium. functional and histologic end-points were blindly assessed 6 weeks later, and hearts were processed for gene profiling. Genes differentially expressed between control hearts and hESC-Pg–treated and EV-treated hearts were clustered into functionally relevant pathways. Results At 6 weeks after hESC-Pg administration, treated mice had significantly reduced left ventricular end-systolic (−4.20 ± 0.96 µl or −7.5%, p = 0.0007) and end-diastolic (−4.48 ± 1.47 µl or −4.4%, p = 0.009) volumes compared with baseline values despite the absence of any transplanted hESC-Pg or human embryonic stem cell–derived cardiomyocytes in the treated mouse hearts. Equal benefits were seen with the injection of hESC-Pg–derived EV, whereas animals injected with alpha-MEM (vehicle control) did not improve significantly. Histologic examination suggested a slight reduction in infarct size in hESC-Pg–treated animals and EV-treated animals compared with alpha-MEM–treated control animals. In the hESC-Pg–treated and EV-treated groups, heart gene profiling identified 927 genes that were similarly upregulated compared with the control group. Among the 49 enriched pathways associated with these up-regulated genes that could be related to cardiac function or regeneration, 78% were predicted to improve cardiac function through increased cell survival and/or proliferation or DNA repair as well as pathways related to decreased fibrosis and heart failure. Conclusions In this post-infarct heart failure model, either hESC-Pg or their secreted EV enhance recovery of cardiac function and similarly affect cardiac gene expression patterns that could be related to this recovery. Although the mechanisms by which EV improve cardiac function remain to be determined, these results support the idea that a paracrine mechanism is sufficient to effect functional recovery in cell-based therapies for post-infarction–related chronic heart failure.
Published: 2016
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33. Does the Flow Know? Mitral Regurgitant Jet Direction and Need for Valve Repair in Hypertrophic Obstructive Cardiomyopathy

Author: Robert A. Levine, Ehud Schwammenthal, and Albert Hagège
Subjects: medicine.medical_specialty, Jet (fluid), Extramural, business.industry, Cardiomyopathy, Mitral Valve Insufficiency, Cardiomyopathy, Hypertrophic, medicine.disease, Obstructive cardiomyopathy, Echocardiography, Doppler, Flow (mathematics), Internal medicine, medicine, Cardiology, Humans, Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine, business
Published: 2019

34. Influence of centre expertise on the diagnosis and management of hypertrophic cardiomyopathy A study from the French register of hypertrophic cardiomyopathy (REMY)

Author: Claudio Cervino, Gilbert Habib, Thibaud Damy, Lucile Offredo, Muriel Tafflet, Erwan Donal, Patricia Reant, Jean-Christophe Eicher, Mariana Mirabel, Fabien Labombarda, Albert Hagège, Philippe Charron, Geltrude Giura, Xavier Jouven, Marianna Laurito, Xavier Jeunemaitre, Jean-Philippe Empana, Michel Desnos, Olivier Huttin, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Sorbonne Paris Cité (USPC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Esquirol [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de génétique [CHU HEGP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance Publique - Hôpitaux de Marseille (APHM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Sanofi Genzyme, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN)
Subjects: Male, Sarcomeres, medicine.medical_specialty, Genotype, DNA Mutational Analysis, Magnetic Resonance Imaging, Cine, Inherited heart disease, macromolecular substances, 030204 cardiovascular system & hematology, Gene mutation, Myosins, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Medical practice, medicine, In real life, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Genetic Testing, Prospective Studies, Registries, cardiovascular diseases, Cardiac Surgical Procedures, Genetic testing, medicine.diagnostic_test, business.industry, Hypertrophic cardiomyopathy, Disease Management, Cardiomyopathy, Hypertrophic, Middle Aged, medicine.disease, Prognosis, 3. Good health, Current management, Mutation, cardiovascular system, Female, Cardiology and Cardiovascular Medicine, business, Tomography, X-Ray Computed, Follow-Up Studies
Abstract: International audience; Background - Our knowledge of hypertrophic cardiomyopathy (HCM) mainly originates from quarternary centres. The objective is to assess the current management of HCM patients in a large multicentre French register according to the level of expertise. Methods and results - A total of 1431 HCM patients were recruited across 26 (11 expert and 15 non-expert) centres in REMY, a prospective hospital-based register of adult HCM patients. A sarcomeric origin was suspected in 1284 (89.7%) patients [261 (20.3%) with a reported gene mutation, 242 (18.8%) genotype-negative], while 107 (7.5%) had a diagnosis of non-sarcomeric HCM. Patients managed in non-expert centres were older (P
Published: 2019
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35. Fabry disease in cardiology practice: Literature review and expert point of view

Author: Albert Hagège, Dominique P. Germain, Patricia Reant, Gilles Barone-Rochette, Gilles Soulat, Erwan Donal, Gilbert Habib, and Thibaud Damy
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Cardiology, 030204 cardiovascular system & hematology, Gene mutation, Left ventricular hypertrophy, Sudden death, Ventricular Function, Left, Diagnosis, Differential, 03 medical and health sciences, Electrocardiography, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, Humans, Enzyme Replacement Therapy, 030212 general & internal medicine, Aged, Ventricular Remodeling, business.industry, Hypertrophic cardiomyopathy, General Medicine, Enzyme replacement therapy, Cardiomyopathy, Hypertrophic, Middle Aged, medicine.disease, Implantable cardioverter-defibrillator, Prognosis, Fabry disease, Magnetic Resonance Imaging, 3. Good health, Echocardiography, Heart failure, Fabry Disease, Female, Hypertrophy, Left Ventricular, Cardiology and Cardiovascular Medicine, business
Abstract: Fabry disease is an X-linked progressive multisystemic genetic sphingolipidosis caused by deficient activity of lysosomal α-galactosidase A. Men aged>30 years and women aged>40 years most often present with unexplained left ventricular hypertrophy, usually concentric and non-obstructive, but sometimes mimicking sarcomeric hypertrophic cardiomyopathy, particularly when isolated, as in the cardiac or late-onset variant of the disease. In hypertrophic cardiomyopathy cohorts, up to 1% of patients have been diagnosed with Fabry disease. Frequent cardiac symptoms include chronotropic incompetence, severe conduction disturbances and arrhythmias, heart failure and sudden death, and cardiovascular complications are currently the leading cause of death at a mean age of 55 years in men and 66 years in women. Complementary to screening for extracardiac manifestations, the initial cardiac evaluation should include long-duration electrocardiogram recordings, echocardiography and late gadolinium and T1 mapping magnetic resonance imaging. Abnormalities of a non-hypertrophied inferolateral wall at the base of the left ventricle (thinning, decreased strain, midwall fibrosis) and low native T1 signal on magnetic resonance imaging are evocative. Aggressive cardiac management may include the control of cardiovascular risk factors, anticoagulation, permanent cardiac pacing and/or an implantable cardioverter defibrillator device, while antiarrhythmics and beta-blockers should be used with caution. Specific therapy should be initiated at the earliest stage, when the first structural or functional cardiac abnormalities are detected, and should include enzyme replacement therapy (available since 2001) or chaperone therapy (available since 2016) (the use of which is limited to patients with Fabry disease and an amenable α-galactosidase A [GLA] gene mutation).
Published: 2018

36. Protein-losing gastropathy associated with cytomegalovirus in two sisters - Case reports and review of the literature

Author: Camille Jung, S. Verlhac, H. Hagège, Fouad Madhi, C. Tard, and Ralph Epaud
Subjects: medicine.medical_specialty, Abdominal pain, Congenital cytomegalovirus infection, Gastroenterology, Endoscopy, Gastrointestinal, 03 medical and health sciences, Hypoproteinemia, 0302 clinical medicine, hemic and lymphatic diseases, 030225 pediatrics, Internal medicine, Edema, medicine, Humans, Hypoalbuminemia, Child, Gastritis, Hypertrophic, business.industry, Siblings, medicine.disease, Ménétrier's disease, Child, Preschool, Pediatrics, Perinatology and Child Health, Cytomegalovirus Infections, Vomiting, Female, medicine.symptom, business, Nephrotic syndrome
Abstract: Menetrier's disease is a protein-losing gastropathy that is uncommon in childhood. Its symptoms are unspecific, with abdominal pain, vomiting, and edema. Blood tests show hypoproteinemia and hypoalbuminemia, and upper digestive endoscopy reveals giant gastric folds. In children, cytomegalovirus has been identified as a possible cause. Here we describe two sisters presenting with Menetrier's disease, 2 years apart. This diagnosis should be considered in the presence of hypoalbuminemia in children when a nephrotic syndrome is excluded.
Published: 2018

37. New insights into mitral valve dystrophy: a Filamin-A genotype-phenotype and outcome study

Author: Jean Noël Trochu, Vincent Probst, Jan J.J. Aalberts, Susan A. Slaugenhaupt, Elena Aikawa, Thierry Le Tourneau, Solena Le Scouarnec, Hubert Desal, Simon Lecointe, Francesca N. Delling, Christian Dina, Hervé Le Marec, Ousama Al Habash, Russell A. Norris, Roger R. Markwald, Toon Oomen, Xavier Jeunemaitre, Caroline Cueff, Albert J. H. Suurmeijer, Jonathan A. Bernstein, Robert A. Levine, F. Kyndt, Matilde Karakachoff, Jean Mérot, Romain Capoulade, Albert Hagège, David J. Milan, Jean Christian Roussel, Daniel Bernstein, Jean-Jacques Schott, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of mathematics and computing science [Eindhoven], Eindhoven University of Technology [Eindhoven] (TU/e), Department of Computer Science, University of Illinois at Chicago, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Cardiovascular Research Center, Massachusetts General Hospital [Boston], Service de génétique [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École nationale supérieure d'architecture de Paris-Belleville (ENSA PB), Department of Pediatrics [Stanford], Stanford Medicine, Stanford University-Stanford University, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Montréal, QC G1V 4G5, Canada, Therapie Cellulaire en Pathologie Cardio-Vasculaire (UMR_S 633), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Department of Pediatrics (School of Medicine), and Stanford University [Stanford]
Subjects: 0301 basic medicine, Male, Heart disease, PROLAPSE, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, REGURGITATION, 0302 clinical medicine, Degenerative disease, Risk Factors, Mitral valve, Mitral valve prolapse, FLNA, ComputingMilieux_MISCELLANEOUS, RISK, Mitral Valve Prolapse, ASSOCIATION, Middle Aged, Prognosis, 3. Good health, Cardiac surgery, medicine.anatomical_structure, Phenotype, Echocardiography, Cardiology, cardiovascular system, Mitral Valve, Female, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Adolescent, Genotype, Filamins, Diastole, HEART-DISEASE, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Journal Article, LOCUS, Humans, Retrospective Studies, business.industry, MUTATIONS, Dystrophy, medicine.disease, 030104 developmental biology, XQ28, MYXOMATOUS VALVULAR DYSTROPHY, Mutation, business
Abstract: International audience; Aims: Filamin-A (FLNA) was identified as the first gene of non-syndromic mitral valve dystrophy (FLNA-MVD). We aimed to assess the phenotype of FLNA-MVD and its impact on prognosis. Methods and results: We investigated the disease in 246 subjects (72 mutated) from four FLNA-MVD families harbouring three different FLNA mutations. Phenotype was characterized by a comprehensive echocardiography focusing on mitral valve apparatus in comparison with control relatives. In this X-linked disease valves lesions were severe in men and moderate in women. Most men had classical features of mitral valve prolapse (MVP), but without chordal rupture. By contrast to regular MVP, mitral leaflet motion was clearly restricted in diastole and papillary muscles position was closer to mitral annulus. Valvular abnormalities were similar in the four families, in adults and young patients from early childhood suggestive of a developmental disease. In addition, mitral valve lesions worsened over time as encountered in degenerative conditions. Polyvalvular involvement was frequent in males and non-diagnostic forms frequent in females. Overall survival was moderately impaired in men (P = 0.011). Cardiac surgery rate (mainly valvular) was increased (33.3 ± 9.8 vs. 5.0 ± 4.9%, P \textless 0.0001; hazard ratio 10.5 [95% confidence interval: 2.9-37.9]) owing mainly to a lifetime increased risk in men (76.8 ± 14.1 vs. 9.1 ± 8.7%, P \textless 0.0001). Conclusion: FLNA-MVD is a developmental and degenerative disease with complex phenotypic expression which can influence patient management. FLNA-MVD has unique features with both MVP and paradoxical restricted motion in diastole, sub-valvular mitral apparatus impairment and polyvalvular lesions in males. FLNA-MVD conveys a substantial lifetime risk of valve surgery in men.
Published: 2018
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38. Effects of Age on Treatment of Chronic Hepatitis C with Direct Acting Antivirals

Author: Christophe Pilette, Yann Le-Bricquir, Frédéric Heluwaert, Isabelle Rosa-Hézode, Jean-Pierre Arpurt, Jean Henrion, Bruno Lesgourgues, Bertrand Condat, Gilles Macaigne, Georges Barjonet, Christophe Renou, Hervé Hagège, Ramuntxo Arotcarena, E. Maringe, Bertrand Tissot, Stéphanie de Montigny-Lenhardt, Edmond Geagea, Alexandre Pariente, Séverine Hommel, Frangois Bourhis, Xavier Causse, Jean-Frangois Cadranel, Hatem Salloum, Marie-Pierre Ripault, Arnaud Pauwels, H. Labadie, Andre-Jean Remy, Hortensia Lison, Vincent Jouannaud, Matthieu Schnee, and David Zanditenas
Subjects: Simeprevir, Male, Pyrrolidines, Sofosbuvir, Specialties of internal medicine, Hepacivirus, Comorbidities, Sustained Virological Response, chemistry.chemical_compound, 0302 clinical medicine, Prospective Studies, Prospective cohort study, Patients-reported outcomes, Age Factors, Imidazoles, Valine, General Medicine, Middle Aged, Hospitals, Survival Rate, Prospective, Treatment Outcome, RC581-951, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, France, medicine.drug, Ledipasvir, medicine.medical_specialty, Daclatasvir, Genotype, Antiviral Agents, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, Patient Reported Outcome Measures, General, Adverse effect, Aged, Fluorenes, Hepatology, business.industry, Hepatitis C, Chronic, medicine.disease, chemistry, DNA, Viral, Benzimidazoles, Carbamates, Morbidity, business, Follow-Up Studies
Abstract: Introduction and aim Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. Material and methods A prospective cohort of adult patients with CHC treated in French general hospitals. Results Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. Conclusions The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.
Published: 2018

39. Mutations in DCHS1 Cause Mitral Valve Prolapse

Author: Yaopan Mao, Katelynn Toomer, Charles Simpson, David J. Milan, David S. Peal, Francesca N. Delling, Roger R. Markwald, Jorge Solis, Maelle Perrocheau, Ronen Durst, Lisa A. Freed, Amanda J. Johnson, Annemarieke DeVlaming, Christopher Jett, Xavier Estivill, Leticia Fernández-Friera, Adrian H. Chester, Michel Pucéat, Matthew R. Stone, Maire Leyne, Thierry Le Tourneau, Susan A. Slaugenhaupt, Christian Dina, Jean-Jacques Schott, Monica Salani, Kenneth D. Irvine, Katherine Williams, Kimberly Sauls, Andy Wessels, Yoshikazu Tsukasaki, Daniel Trujillano, Xingju Nie, Herve LeMarec, Florie A. Charles, Patrick Bruneval, Donald R. Menick, Robert A. Levine, Stephan Ossowski, Russell A. Norris, Michael E. Talkowski, Harinath Kasiganesan, Nabila Bouatia-Naji, Ann-Marie Broome, Stacey N. Lynch, Tahirali Motiwala, Harrison Brand, Christophe Tribouilloy, Colby Chiang, Albert Hagège, Xavier Jeunemaitre, Center for humana genetic research, Harvard Medical School [Boston] (HMS), Dipartimento di Biologia Cellulare e dello Sviluppo, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laser Processing Group, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires (LRI - EA4062), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Università degli Studi di Roma 'La Sapienza' [Rome], Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: Male, Pathology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Messenger, 030204 cardiovascular system & hematology, medicine.disease_cause, Mice, 0302 clinical medicine, Cell Movement, Mitral valve, Missense mutation, Mitral valve prolapse, Atrioventricular canal defect, Pair 11, Zebrafish, Genetics, 0303 health sciences, Mutation, Multidisciplinary, Mitral Valve Prolapse, Protein Stability, Cadherins, 3. Good health, Pedigree, medicine.anatomical_structure, Phenotype, cardiovascular system, Mitral Valve, Female, Human, medicine.medical_specialty, Cadherin Related Proteins, Biology, Chromosomes, Article, 03 medical and health sciences, medicine, Animals, Humans, RNA, Messenger, 030304 developmental biology, Body Patterning, Mitral regurgitation, Mitral valve repair, DCHS1, Chromosomes, Human, Pair 11, Zebrafish Proteins, medicine.disease, RNA
Abstract: International audience; Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals. It can manifest as mitral regurgitation and is the leading indication for mitral valve surgery. Despite a clear heritable component, the genetic aetiology leading to non-syndromic MVP has remained elusive. Four affected individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of the linked interval on chromosome 11. We report a missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds), that segregates with MVP in the family. Morpholino knockdown of the zebrafish homologue dachsous1b resulted in a cardiac atrioventricular canal defect that could be rescued by wild-type human DCHS1, but not by DCHS1 messenger RNA with the familial mutation. Further genetic studies identified two additional families in which a second deleterious DCHS1 mutation segregates with MVP. Both DCHS1 mutations reduce protein stability as demonstrated in zebrafish, cultured cells and, notably, in mitral valve interstitial cells (MVICs) obtained during mitral valve repair surgery of a proband. Dchs1(+/-) mice had prolapse of thickened mitral leaflets, which could be traced back to developmental errors in valve morphogenesis. DCHS1 deficiency in MVP patient MVICs, as well as in Dchs1(+/-) mouse MVICs, result in altered migration and cellular patterning, supporting these processes as aetiological underpinnings for the disease. Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease.
Published: 2015
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40. 2014 ESC GUIDELINES ON DIAGNOSIS AND MANAGEMENT OF HYPERTROPHIC CARDIOMYOPATHY

Author: Heiko Mahrholdt, Petros Nihoyannopoulos, Philippe Charron, Franco Cecchi, Michael A. Borger, Petronella G. Pieper, Christoph Tillmanns, Albert A. Hagège, Stefano Nistri, Giuseppe Limongelli, Claudio Rapezzi, Perry M. Elliott, Constantinos O'Mahony, Antoine Lafont, Martin Borggrefe, Frans H. Rutten, Aris Anastasakis, William J. McKenna, J Mogensen, Hugh Watkins, and Burkert Pieske
Subjects: Ablation Techniques, diagnosis, Heart Valve Diseases, heart failure, Arrhythmias, Cardiovascular, Sports Medicine, valve disease, Sudden cardiac death, Electrocardiography, Risk Factors, genetics, Child, Medical History Taking, Cardiac imaging, biology, Prenatal Care, Arrhythmia, Athletes, Diagnosis, Genetics, Guideline, Heart failure, Hypertension, Implantable cardioverter defibrillators, Left ventricular outflow tract obstruction, Pregnancy, Symptoms, Valve disease, Adult, Angina Pectoris, Arrhythmias, Cardiac, Cardiac Imaging Techniques, Cardiac Pacing, Artificial, Cardiomyopathy, Hypertrophic, Clinical Laboratory Techniques, Death, Sudden, Cardiac, Delivery of Health Care, Diagnosis, Differential, Female, Genetic Counseling, Genetic Testing, Heart Failure, Humans, Pedigree, Physical Examination, Preconception Care, Pregnancy Complications, Cardiovascular, Syncope, Thoracic Surgical Procedures, Ventricular Outflow Obstruction, Cardiology and Cardiovascular Medicine, Death, Artificial, Cardiology, pregnancy, Cardiac, guideline, medicine.medical_specialty, hypertension, Cardiomyopathy, arrhythmia, cardiac imaging, sudden cardiac death, implantable cardioverter defibrillators, Internal medicine, left ventricular outflow tract obstruction, medicine, Diseases of the circulatory (Cardiovascular) system, business.industry, biology.organism_classification, medicine.disease, Sudden, Pregnancy Complications, athletes, Hypertrophic, RC666-701, Differential, symptoms, Cardiac Pacing, business
Published: 2015

41. Rupture of mitral valve chordae in hypertrophic cardiomyopathy

Author: Elisabeth Riant, Florence Boissier, Anh Tuan Nguyen, Michel Desnos, Patrick Bruneval, Albert Hagège, Guy Achkouty, and Jean-Noël Fabiani
Subjects: Male, Mitral Valve Annuloplasty, Cardiomyopathie hypertrophique, medicine.medical_treatment, Heart Rupture, Severity of Illness Index, Plastie mitrale, Risk Factors, Mitral valve, Prevalence, Heart Valve Prosthesis Implantation, Hypertrophic cardiomyopathy, Mitral Valve Insufficiency, General Medicine, Middle Aged, Echocardiography, Doppler, Treatment Outcome, medicine.anatomical_structure, cardiovascular system, Cardiology, Chordae Tendineae, Mitral Valve, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Chordal rupture, Paris, medicine.medical_specialty, Rupture de cordage mitral, Ventricular outflow tract obstruction, Myxomatous degeneration, Predictive Value of Tests, Internal medicine, medicine, Humans, cardiovascular diseases, Mitral regurgitation, Aged, Retrospective Studies, Mitral valve repair, business.industry, Insuffisance mitrale, Cardiomyopathy, Hypertrophic, medicine.disease, Aged patients, Obstructive hypertrophic cardiomyopathy, business
Abstract: Summary Background While occasional reports of mitral valve chordal rupture have been described in hypertrophic cardiomyopathy, the exact prevalence and characteristics of this event in a large medical cohort have not been reported. Aim To assess the prevalence of mitral valve chordal rupture in hypertrophic cardiomyopathy and the clinical, echocardiographic, surgical and histological profiles of those patients. Methods We searched for patients with mitral valve chordal rupture diagnosed by echocardiography among all electronic files of patients admitted to our centre for hypertrophic cardiomyopathy between 2000 and 2010. Results Among 580 patients admitted for hypertrophic cardiomyopathy, six patients (1%, 5 men, age 68–71 years) presented with mitral valve chordal rupture, symptomatic in five cases, always involving the posterior mitral leaflet. In all cases, echocardiography before rupture showed mitral valve systolic anterior motion, with anterior (and not posterior) leaflet elongation compared with a random sample of patients with non-obstructive hypertrophic cardiomyopathy ( P = 0.006) (and similar to that observed in obstructive hypertrophic cardiomyopathy). Significant resting left ventricular outflow tract obstruction was always present before rupture and disappeared after rupture in the five cases requiring mitral valve surgery for severe mitral regurgitation. Histological findings were consistent with extensive myxomatous degeneration in all cases. Conclusion Mitral valve chordal rupture is: infrequent in hypertrophic cardiomyopathy; occurs in aged patients with obstructive disease; involves, essentially, the posterior mitral leaflet; and causes, in general, severe mitral regurgitation requiring surgery. Myxomatous degeneration may be the substrate for rupture in these patients.
Published: 2015
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42. Pocket-sized focused cardiac ultrasound: Strengths and limitations

Author: David S. Celermajer, Anne-Sophie Beraud, Mariana Mirabel, Albert Hagège, Xavier Jouven, and Eloi Marijon
Subjects: Out of hospital, Focused cardiac ultrasound, medicine.medical_specialty, business.industry, Heart failure, Equipment Design, General Medicine, Education, Surgery, Clinical Practice, Échocardiographie cardiaque, Software portability, Echocardiography, Médecine d’urgence, medicine, Humans, Emergency medicine, Échoscopie, Éducation, Medical physics, business, Cardiology and Cardiovascular Medicine
Abstract: SummaryFocused cardiac ultrasound (FCU) has emerged in recent years and has created new possibilities in the clinical assessment of patients both in and out of hospital. The increasing portability of echocardiographic devices, with some now only the size of a smartphone, has widened the spectrum of potential indications and users, from the senior cardiologist to the medical student. However, many issues still need to be addressed, especially the acknowledgment of the advantages and limitations of using such devices for FCU, and the extent of training required in this rapidly evolving field. In recent years, an increasing number of studies involving FCU have been published with variable results. This review outlines the evidence for the use of FCU with pocket-echo to address specific questions in daily clinical practice.
Published: 2015
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43. GLA-Ring Opportunities and Challenges for Fabry Disease ∗

Author: Daniel P. Judge, Ike S. Okwuosa, and Albert A. Hagège
Subjects: medicine.medical_specialty, Alpha-galactosidase, biology, business.industry, Cardiomyopathy, 030204 cardiovascular system & hematology, medicine.disease, Ring (chemistry), Left ventricular hypertrophy, Fabry disease, 03 medical and health sciences, 0302 clinical medicine, alpha-Galactosidase, Internal medicine, Mutation, Mutation (genetic algorithm), medicine, Cardiology, biology.protein, Fabry Disease, Humans, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business
Published: 2016
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44. Suggestion of self-(in)coherence modulates cognitive dissonance

Author: Lionel Naccache, Mariam Chammat, Joshua Hagège, Caroline Tandetnik, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurophysiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL UPMC, Gestionnaire, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, Social psychology (sociology), Preference change, Sense of Coherence, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Memory, Episodic, lcsh:Medicine, 050109 social psychology, Models, Psychological, Choice Behavior, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cognitive dissonance, Humans, 0501 psychology and cognitive sciences, lcsh:Science, Suggestion, Episodic memory, media_common, Multidisciplinary, lcsh:R, 05 social sciences, Coherence (philosophical gambling strategy), [SDV] Life Sciences [q-bio], Linear Models, lcsh:Q, Female, Consciousness, Psychology, 030217 neurology & neurosurgery, Photic Stimulation, Sense of coherence, Cognitive psychology, Cognitive Dissonance
Abstract: International audience; While cognitive dissonance is an influential concept of social psychology, its relations with consciousness and episodic memory remain strongly debated. We recently used the free-choice paradigm (FCP) to demonstrate the crucial role of conscious memory of previous choices on choice-induced preference change (CIPC). After choosing between two similarly rated items, subjects reevaluated chosen items as more attractive, and rejected items as less attractive. However such a CIPC was present exclusively for items that were correctly remembered as chosen or rejected during the choice stage, both in healthy controls and in amnesic patients. In the present work, we show that CIPC can be modulated by suggestive quotes promoting self-coherence or self-incoherence. In addition to the crucial role of memory of previous choices, we discovered that memory of the suggestive quotes was correlated to the modulation of CIPC. Taken together these results suggest that CIPC reflects a dynamic homeostatic regulation of self-coherence.
Published: 2018
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45. Hepatitis C treatment with all-oral direct-acting antivirals: Effectiveness and tolerance in a multicenter, prospective, observational study from French general hospitals (APROVVIE, ANGH)

Author: Gilles Macaigne, Bruno Lesgourgues, H. Labadie, Jean-Pierre Arpurt, David Zanditenas, Marie-Pierre Ripault, Bertrand Condat, Bertrand Tissot, Jean Henrion, Jean-François Cadranel, Ramuntxo Arotcarena, Frédéric Heluwaert, Xavier Causse, Arnaud Pauwels, F. Bourhis, Hervé Hagège, Matthieu Schnee, Edmond Geagea, Christophe Renou, Alexandre Pariente, Yann Le eaBricquir, Georges Barjonet, Vincent Jouannaud, Isabelle Rosa-Hézode, André-Jean Remy, Christophe Pilette, Hatem Salloum, Hortensia Lison, Séverine Hommel, E. Maringe, and Stéphanie de Montigny-Lenhardt
Subjects: Simeprevir, Ledipasvir, Adult, Male, medicine.medical_specialty, Daclatasvir, Sofosbuvir, Adolescent, Population, Administration, Oral, Hospitals, General, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, education, Aged, Aged, 80 and over, education.field_of_study, Dasabuvir, business.industry, Ribavirin, General Medicine, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Treatment Outcome, chemistry, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, France, business, medicine.drug
Abstract: Summary Background and aims According to clinical trials, the treatment of patients with chronic hepatitis C (CHC) with second-generation direct acting antiviral agents (DAAs) is highly efficient and well tolerated. The goal of this study was to investigate the effectiveness and safety of various combinations of these drugs during their first 2 years of use in the real-world practice of French general hospitals. Methods Data from patients treated with all-oral DAAs in 24 French non-academic hospital centers from March 1, 2014 to January 1, 2016, were prospectively recorded. The sustained virological response 12–24 weeks after treatment (SVR 12-24) was estimated and severe adverse events (SAE) were evaluated and their predictive factors were determined using logistic regression. Results Data from 1123 patients were analyzed. The population was 69% genotype (G) 1, 13% G3, 11.5% G4, 5% G2, 49% with cirrhosis and 55% treatment-experienced. The treatment regimens were sofosbuvir/ledipasvir (38%), sofosbuvir/daclatasvir (32%), sofosbuvir/simeprevir (17%), ombitasvir + paritaprevir + ritonavir (5%) (with dasabuvir 3.5%), and sofosbuvir/ribavirin (8%). Ribavirin was given to 24% of patients. The SVR 12-24 was 91.0% (95% CI: 89.2–92.5%). Sofosbuvir-ribavirin was less effective than other regimens. The independent predictors of SVR 12-24 by logistic regression were body weight, albumin, previous hepatocellular carcinoma and treatment regimen (sofosbuvir/ribavirin vs. others). Sixty-four severe adverse events (SAE) were observed in 59 [5.6%] patients, and were independently predicted by cirrhosis and baseline hemoglobin. Serum creatinine increased during treatment (mean 8.5%, [P Conclusions Second generation DAAs combinations are as effective and well tolerated in a « real-world » population as in clinical trials. Further studies are needed on renal tolerance.
Published: 2018

46. Long-Term Engraftment (16 Years) of Myoblasts in a Human Infarcted Heart

Author: Gilles Soulat, Marie Crahès, Philippe Menasché, Michel Desnos, Jean-Thomas Vilquin, Jean-Pierre Marolleau, Marie-Cécile Bories, Albert Hagège, Patrick Bruneval, Jérôme Larghero, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), CHU Amiens-Picardie, Therapie Cellulaire en Pathologie Cardio-Vasculaire (UMR_S 633), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre de recherche en Myologie – U974 SU-INSERM
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Myoblasts, Skeletal, Muscle Fibers, Skeletal, Myocardial Infarction, Heart failure, 030204 cardiovascular system & hematology, Ventricular Function, Left, Myoblasts, 03 medical and health sciences, 0302 clinical medicine, Troponin T, Human Clinical Article, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Fibrosis, Internal medicine, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Myocyte, Humans, Muscle, Skeletal, Pathological, Long-term follow-up, Heart transplantation, Myosin Heavy Chains, Myogenesis, business.industry, Myocardium, fungi, Cell Biology, General Medicine, Long‐term follow‐up, medicine.disease, Transplantation, 030104 developmental biology, Cardiology, Clinical cell transplantation, Stem cell, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Developmental Biology
Abstract: We report the case of a patient who had undergone injections of myoblasts in an infarct area 16 years before being referred for heart transplantation. The pathological examination of the explanted heart found persisting myotubes embedded in fibrosis. This finding supports the ability of myoblasts to survive in harsh environments, which can make them appealing candidates for transplantation in diseases requiring supply of new myogenic cells.
Published: 2018
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47. [Hepatitis C in prison: an opportunity for healthcare]

Author: Méoïn, Hagège
Subjects: Prisoners, Prisons, Humans, France, Hepatitis C, Chronic, Vulnerable Populations
Abstract: Prison inmates constitute a vulnerable population, in which socially excluded, poor and marginalized individuals are overrepresented and infectious diseases are more prevalent than in the general population. The poor health of inmates and recently released inmates is a rarely studied public health problem. The health trajectories of inmates living with the hepatitis C virus is an interesting case study to discuss public health interventions in prison. It is presented here as part of a socio-anthropological study of inmates and healthcare professionals in France. These trajectories shed light on treatment and healthcare experiences, within their economic, social, material and institutional constraints. They are an integral part of the public debate on prison health in France, comprising two prominent positions : the "pathogenic prison" and the "healing prison". These extreme positions in the broader context of this debate provide a better understanding of the context and obstacles to public health initiatives in prison and suggest ways to make them more effective.
Published: 2017

48. Coronary lesions in refractory out of hospital cardiac arrest (OHCA) treated by extra corporeal pulmonary resuscitation (ECPR)

Author: Romain Jouffroy, Christian Spaulding, Lionel Lamhaut, Xavier Jouven, Kim An, Victoria Tea, Albert Hagège, Pierre Carli, C. Dagron, Jean-Herlé Raphalen, Alice Hutin, Frédéric J. Baud, Nicolas Danchin, Alain Cariou, and Etienne Puymirat
Subjects: Adult, Male, medicine.medical_specialty, Emergency Medical Services, medicine.medical_treatment, Comorbidity, Coronary Artery Disease, 030204 cardiovascular system & hematology, Emergency Nursing, Revascularization, Coronary Angiography, Out of hospital cardiac arrest, Time-to-Treatment, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Extracorporeal Membrane Oxygenation, Refractory, Statistical significance, Internal medicine, medicine, Humans, Extracorporeal cardiopulmonary resuscitation, Prospective Studies, Aged, business.industry, Percutaneous coronary intervention, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Cardiopulmonary Resuscitation, Cohort, Emergency Medicine, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Out-of-Hospital Cardiac Arrest
Abstract: Purpose Extracorporeal cardiopulmonary resuscitation (ECPR) is a second line treatment for refractory cardiac arrest (R-OHCA). Timing of ECPR before performing coronary angiography (CAG) is still debated. The aim of the study was to describe the clinical and angiographic characteristics of the largest cohort of out-of-hospital cardiac arrest (OHCA) patients undergoing ECPR. Methods All refractory OHCA patients with ECPR managed by the prehospital mobile intensive care unit (MoICU of the SAMU) in Paris (France) were prospectively included from October 2014 to December 2016. Results Among 74 patients included over the period, 54 patients had coronary artery disease (CAD). There is a trend toward the CAD patients being older but it did not meet statistical significance (55.3 ± 11.8 vs. 50.6 ± 12.8, p = 0,14). Patients were more frequently men and smokers (p = 0.03 for both). The proportion of initial shockable rhythm tended to be higher in patients with CAD (71% vs. 55%). The rate of 1-, 2-, and 3-vessel disease were 43%, 35% and 22% respectively. The Syntax Score was 18 ± 9 and the lesions in each epicardial vessel were mainly proximal. Percutaneous coronary intervention was performed ad hoc in 49 patients (91%). Complete revascularization was performed in 64%. Inhospital death was numerically lower (65% vs. 75%) in patients with CAD, especially in patients with initial shockable rhythm. Conclusion In 74 refractory OHCA patients treated with ECPR implanted by a prehospital mobile intensive care unit, the rate of CAD was high (54/74) especially in patients with shockable rhythm. The majority of patients presented with double or triple vessel disease and proximal lesions. The severity and extension of CAD may explain the refractory nature of the cardiac arrest.
Published: 2017

49. Effect of Losartan on Mitral Valve Changes After Myocardial Infarction

Author: Suzanne Sullivan, Mark D. Handschumacher, Philipp E. Bartko, J. Luis Guerrero, Jill Wylie-Sears, Margo M. Seybolt, Whitney S. Irvin, Dae-Hee Kim, Catherine Szymanski, Robert A. Levine, Elena Aikawa, Albert Hagège, Joyce Bischoff, Michael L. Garcia, Emmanuel Messas, Jonathan Beaudoin, Jacob P. Dal-Bianco, Alain Carpentier, and James S. Titus
Subjects: 0301 basic medicine, medicine.medical_specialty, Echocardiography, Three-Dimensional, Myocardial Infarction, Myocardial Ischemia, Article, Losartan, 03 medical and health sciences, Transforming Growth Factor beta, Fibrosis, Mitral valve, Internal medicine, medicine, Animals, Humans, Myocardial infarction, Papillary muscle, Mitral regurgitation, Sheep, Ventricular Remodeling, business.industry, Endothelial Cells, Mitral Valve Insufficiency, Papillary Muscles, medicine.disease, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Blood pressure, Heart failure, cardiovascular system, Cardiology, Mitral Valve, Cardiology and Cardiovascular Medicine, business, Angiotensin II Type 1 Receptor Blockers, medicine.drug
Abstract: After myocardial infarction (MI), mitral valve (MV) tethering stimulates adaptive leaflet growth, but counterproductive leaflet thickening and fibrosis augment mitral regurgitation (MR), doubling heart failure and mortality. MV fibrosis post-MI is associated with excessive endothelial-to-mesenchymal transition (EMT), driven by transforming growth factor (TGF)-β overexpression. In vitro, losartan-mediated TGF-β inhibition reduces EMT of MV endothelial cells.This study tested the hypothesis that profibrotic MV changes post-MI are therapeutically accessible, specifically by losartan-mediated TGF-β inhibition.The study assessed 17 sheep, including 6 sham-operated control animals and 11 with apical MI and papillary muscle retraction short of producing MR; 6 of the 11 were treated with daily losartan, and 5 were untreated, with flexible epicardial mesh comparably limiting left ventricular (LV) remodeling. LV volumes, tethering, and MV area were quantified by using three-dimensional echocardiography at baseline and at 60 ± 6 days, and excised leaflets were analyzed by histopathology and flow cytometry.Post-MI LV dilation and tethering were comparable in the losartan-treated and untreated LV constraint sheep. Telemetered sensors (n = 6) showed no significant losartan-induced changes in arterial pressure. Losartan strongly reduced leaflet thickness (0.9 ± 0.2 mm vs. 1.6 ± 0.2 mm; p 0.05; 0.4 ± 0.1 mm sham animals), TGF-β, and downstream phosphorylated extracellular-signal-regulated kinase and EMT (27.2 ± 12.0% vs. 51.6 ± 11.7% α-smooth muscle actin-positive endothelial cells, p 0.05; 7.2 ± 3.5% sham animals), cellular proliferation, collagen deposition, endothelial cell activation (vascular cell adhesion molecule-1 expression), neovascularization, and cells positive for cluster of differentiation (CD) 45, a hematopoietic marker associated with post-MI valve fibrosis. Leaflet area increased comparably (17%) in constrained and losartan-treated sheep.Profibrotic changes of tethered MV leaflets post-MI can be modulated by losartan without eliminating adaptive growth. Understanding the cellular and molecular mechanisms could provide new opportunities to reduce ischemic MR.
Published: 2017

50. One year of baclofen in 100 patients with or without cirrhosis: a French real-life experience

Author: Charlotte Costentin, Hervé Hagège, Georges Pulwermacher, Jean-François Cadranel, Françoise Roudot-Thoraval, Mourad Medmoun, Véronique Béhar, Armand Garioud, Hortensia Lison, and Camille Barrault
Subjects: Adult, Male, medicine.medical_specialty, Alcoholic liver disease, Baclofen, Cirrhosis, Time Factors, Alcohol Drinking, Aspartate transaminase, Gastroenterology, Unit of alcohol, 03 medical and health sciences, 0302 clinical medicine, Liver Cirrhosis, Alcoholic, Recurrence, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Adverse effect, Prospective cohort study, Mean corpuscular volume, Hepatology, medicine.diagnostic_test, biology, business.industry, Alcohol Abstinence, Middle Aged, medicine.disease, Alcoholism, Treatment Outcome, Anesthesia, GABA-B Receptor Agonists, biology.protein, Female, France, Liver function tests, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND Several studies have suggested the efficacy of baclofen in reducing alcohol consumption, leading to a temporary recommendation for use in France. AIM Our aim was to report our experience in using baclofen in alcohol-dependant patients with or without liver cirrhosis. PATIENTS AND METHODS Consecutive patients from two liver and alcohol units were recruited over a 3-year period and received increasing doses of baclofen associated with social, psychological, and medical care. RESULTS One hundred patients were treated, of whom 65 were cirrhotic. After 1 year, 86 patients were still being followed up. At a mean dosage of 40 mg/day (extremes: 30-210), the median daily alcohol consumption reduced from 80 to 0 g/day (P
Published: 2017

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