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1. Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study

Author

Naïm Ouldali, Haleh Bagheri, Francesco Salvo, Denise Antona, Antoine Pariente, Claire Leblanc, Martine Tebacher, Joëlle Micallef, Corinne Levy, Robert Cohen, Etienne Javouhey, Brigitte Bader-Meunier, Caroline Ovaert, Sylvain Renolleau, Veronique Hentgen, Isabelle Kone-Paut, Nina Deschamps, Loïc De Pontual, Xavier Iriart, Christelle Gras-Le Guen, François Angoulvant, Alexandre Belot, Aurelie Donzeau, Layal El Aridi, Sophie Lety, Bertrand Leboucher, Agnes Baur, Lucas Jeusset, Maelle Selegny, Cristian Fedorczuk, Marion Lajus, Philippe Bensaid, Yacine Laoudi, Charlotte Pons, Anne-Cécile Robert, Camille Beaucourt, Muriel Richard, Etienne Goisque, Olivier Brissaud, Pierre Segretin, Julie Molimard, Marie-Clothilde Orecel, Gregoire Benoit, Lucille Bongiovanni, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour-Andlauer, Come Horvat, Pierre Poinsot, Cecile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, Florence Villedieu, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Hadile Mutar, Sébastien Rouget, Elodie Nattes, Isabelle Hau, Sandra Biscardi, Houmam El Jurdi, Camille Jung, Denis Semama, Frederic Huet, Anne-Marie Zoccarato, Mayssa Sarakbi, Guillaume Mortamet, Cécile Bost-Bru, Joachim Bassil, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu, Philippe Durand, Pierre Tissiere, Caroline Claude, Guillaume Morelle, Tamazoust Guiddir, Charlotte Borocco, Frédérique Delion, Camille Guillot, Stéphane Leteurtre, François Dubos, Mylene Jouancastay, Alain Martinot, Valentine Voeusler, Jeanne Languepin, Nathalie Garrec, Arnaud Chalvon Demersay, Aurélie Morand, Emmanuelle Bosdure, Noémie Vanel, Fabrice Ughetto, Fabrice Michel, Marie Caujolle, Renaud Blonde, Jacqueline Nguyen, Olivier Vignaud, Caroline Masserot-Lureau, François Gouraud, Carine Araujo, Tara Ingrao, Sanaa Naji, Mohammed Sehaba, Christine Roche, Aurelia Carbasse, Christophe Milesi, Mustapha Mazeghrane, Sandrine Haupt, Cyril Schweitzer, Benedicte Romefort, Elise Launay, Christèle Gras-Le Guen, Ahmed Ali, Nathalie Blot, Antoine Tran, Anne Rancurel, Mickael Afanetti, Sophie Odorico, Deborah Talmud, Anais Chosidow, Anne-Sophie Romain, Emmanuel Grimprel, Marie Pouletty, Jean Gaschignard, Olivier Corseri, Albert Faye, Isabelle Melki, Camille Ducrocq, Cherine Benzoïd, Johanna Lokmer, Stéphane Dauger, Maryline Chomton, Anna Deho, Fleur Lebourgeois, Fabrice Lesage, Florence Moulin, Laurent Dupic, Yael Pinhas, Agathe Debray, Martin Chalumeau, Véronique Abadie, Pierre Frange, Jeremie F Cohen, Slimane Allali, William Curtis, Zahra Belhadjer, Johanne Auriau, Mathilde Méot, Lucile Houyel, Damien Bonnet, Christophe Delacourt, Brigitte Bader Meunier, Pierre Quartier, Youssef Shaim, Laurence Baril, Samuel Crommelynck, Baptiste Jacquot, Philippe Blanc, Natacha Maledon, Blandine Robert, Camille Loeile, Clémence Cazau, Gauthier Loron, Simona Gaga, Cécile Vittot, Loubna El Nabhani, François Buisson, Muriel Prudent, Hugues Flodrops, Fadhila Mokraoui, Simon Escoda, Laurent Bonnemains, Sarah-Louisa Mahi, Clara Mertes, Joelle Terzic, Julie Helms, Charlotte Idier, Soraya Chenichene, Nicoleta Magdolena Ursulescu, Gladys Beaujour, Abdelhak Hakim, Alice Miquel, Agnès Rey, Arnaud Wiedermann, Anne Charbonneau, Agnès Veauvy-Juven, Alexandrine Ferry, Alexis Mandelcwajg, Alix Rousseau, Amandine Prenant, Anne-Laure Bourneuf, Anne Filleron, Audrey Robine, Arthur Félix, Aude Parizel, Aurélie Labarre, Aymeric Cantais, Barbara Ros, Basile Coulon, Blandine Biot, Bérengère Dalichoux, Benjamin Fournier, Benoit Cagnard, Blandine Vanel, David Brossier, Bruno Ménager, Bruno Ozanne, Carole Marie-Jeanne, Camille Bergerot, Camille Chavy, Camille Guidon, Candice Fabre, Caroline Galeotti, Catherine Baker, Claire Ballot-Schmit, Céline Belleau, Céline Charasse, Caroline Favel, Chadia Toumi, Charlène Ferrandiz, Charlotte Couturier, Charlotte Pouchoux, Maryline Chomton-Cailliez, Charlotte Kevorkian-Verguet, Clément Brunet, Céline Manteau, Clémence Mougey, Coline Santy, Coralie Fitament, Charlotte Petriat, Charlotte Rebelle, Cyril Charron, Maxime Dartus, David Toulorge, Cécile Guillou-Debuisson, Dorann Bartebin, Valérie Klein, E Broustal, E Desselas, Elodie Marteau, Emmanuelle Bouvrot, Elise Delacroix, Edeline Coinde, Loubna Elnabhani, Elsa Amouyal, Emilie Chaillou, Emeline Gabilly-Bernard, Emilie Ruiz, Emilie Thibault, Emilie Robin, Etienne Darrieux, Eva Blondel, Floriane Socchi, François Cazassus, Fanny Bajolle, Fatma Lacin, Fouad Madhi, Franck Zekre, François Guerin, Gerald Boussicault, Henri Ginies, Gnansounou Magloire, Guilhem Arnold, Ines Coulognon, Iona Sicard-Cras, Jean-Emmanuel Kahn, Jeanne Bordet, Jeanne-Lise Fausser, Jean-François Baleine, Josephine Brice, Julie Gendras, Kaan Pekin, Karine Norbert, Clément Karsenty, Léa Savary, Laurence Martinat, Léa Lesniewski, Lorelei Charbonnier, Louise Alexandre, Lucas Percheron, Marie Vincenti, Manon Lanzini, Margot Grisval, Marianne Mercy, Marie-Emilie Lampin, Marie Desgranges, Marie Duperril, Marie-Clothilde Orcel, Marion Audier, Marion Favier, Mathieu Carpentier, Mathilde Balcean, Mathilde Bonnet, Maurine Jouret, Marie Delattre, Michael Levy, Michael Valensi, Mickael Shum, Morgane Dumortier, Morgane Gelin, Morgane Nemmouchi, Morgane Williaume, M Sebaha, Nicoleta Genetay-Stanescu, Nathan Giroux, Nicolas Crassard, Neil Derridj, Noemie Lachaume, Oscar Werner, Olivier Guilluy, Olivier Richer, Olivier Tirel, Aurianne Pauvert, Paul Casha, Noémie Perez, Pauline Gras, Pierre-Louis Leger, Marion Pinchou, Pierre Mornand, Prisca Largo, Ramona-Christina Ibanez, Charlotte Roulland, Salam Hadah Albarazi, Said Bichali, Sarah Faton, Amandine Schott, Sébastien Walser, Severine Guillaume, Solene Vincent, Sophie Galene-Gromez, Stanislas Kozisek, Thierry Maugard, Thierry Blanc, Thierry Navarro, Thomas Lauvray, Tamas Kovacs, Valérie Launay, Véronique Despert, Victoria Lhostis, Virginie Gall, Xavier Micaelli, Yasmine Benadjaoud, Zied Matoussi, Hélène Géniaux, Anthony Facile, Tessa Pietri, Pascale Palassin, Sylvine Pinel, Laurent Chouchana, Delphine Callot, Charlène Boulay, Hôpital Robert Debré, CHU Sainte Justine [Montréal], Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Bordeaux population health (BPH), 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), CHU Bordeaux [Bordeaux], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHI Créteil, 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), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [CHU Necker] (RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier de Versailles André Mignot (CHV), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Hôpital Bicêtre, Université Paris-Saclay, CH de Saint-Malo [Broussais], Hôpital Jean Verdier [AP-HP], Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), 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 Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), European Society for Paediatric Infectious Diseases, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [Paris] (Institut IMAGINE/RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Imagine [Paris Necker] (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 (UPC), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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)), and 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)

Subjects
Oncology, [SDV]Life Sciences [q-bio], Health Policy, Multisystem inflammatory syndrome in children, Internal Medicine, COVID-19 mRNA vaccine, BNT162b2, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SARS-COV-2, Hyper-inflammatory syndrome, Child
Abstract

International audience; BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children. METHODS: We conducted a post-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12-17-year-old children between June 15(th), 2021 and January 1(st), 2022, were reported. Cases were reviewed according to WHO criteria for MIS-C. The reporting rate of this syndrome was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. FINDINGS: Up to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 12 presented a hyper-inflammatory syndrome with multisystemic involvement. Main clinical features included male predominance (10/12, 83%), cardiac involvement (10/12, 83%), digestive symptoms (10/12, 83%), coagulopathy (7/12, 58%), cytolytic hepatitis (6/12, 50%), and shock (5/12, 42%). 4/12 (33%) required intensive care unit transfer, and 3/12 (25%) hemodynamic support. All cases recovered. In eight cases, no evidence of previous SARS-CoV-2 infection was found. The reporting rate was 1.5 (95%CI [0.8; 2.6]) per 1,000,000 doses injected, i.e. 2.9 (95%CI [1.5; 5.1]) per 1,000,000 12-17-year-old vaccinated children. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12-17-year-old children infected by SARS-CoV-2. INTERPRETATION: Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12-17-year-old children. The low reporting rate of this syndrome, compared to the rate of post-SARS-CoV-2 MIS-C in the same age-group, largely supports the vaccination in a context of an important circulation of SARS-CoV-2. FUNDING: ESPID Fellowship Award; Grandir-Fonds de Solidarité Pour L'enfance.

Published
2022
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2. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemi

Author

Fanny Bajolle, Diala Khraiche, Caroline Ovaert, Sylvie Falcon-Eicher, Maëlle Selegny, Antoine Legendre, Zahra Belhadjer, Mehdi Oualha, Laurent Bonnemains, Samya Abakka, Sébastien Hascoët, Sylvain Renolleau, Lucile Houyel, Pierre Mauran, Nathan Giroux, Alice Maltret, Gilles Bosser, Sylvie Di Filippo, Bruno Lefort, Julie Wacker, Sophie Malekzadeh-Milani, Pamela Moceri, Damien Bonnet, Jean-Benoit Thambo, Mathilde Meot, Marion Grimaud, Jeanne Bordet, Maurice Beghetti, Johanne Auriau, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), and Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Pediatrics, medicine.medical_specialty, Myocarditis, Ejection fraction, business.industry, Cardiogenic shock, [SDV]Life Sciences [q-bio], Context (language use), 030204 cardiovascular system & hematology, Overweight, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Intensive care, Heart failure, Co 2, Medicine, 030212 general & internal medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, business, ComputingMilieux_MISCELLANEOUS, Asthma
Abstract

Background Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. Methods Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Results Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2–16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was

Published
2021
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3. Heart Development and Congenital Structural Heart Defects

Author

Lucile Houyel, Sigolène M. Meilhac, Centre de Référence des cardiopathies congénitales (M3C), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Morphogenèse du cœur - Heart morphogenesis (Imagine - Institut Pasteur U1163), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Work in the Meilhac laboratory is supported by core funding from the Institut Pasteur and by state funding from the Agence Nationale de la Recherche under the 'Investissements d'avenir' program (ANR-10-IAHU-01 and Inception program ANR-16-CONV-0005)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Meilhac, Sigolène, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, and Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID

Subjects
Heart Defects, Congenital, medicine.medical_specialty, Heart morphogenesis, Heart disease, embryonic heart, First year of life, heart morphogenesis, International Paediatric and Congenital Cardiac Code, ICD-11, Internal medicine, Conotruncal defect, Genetics, Animals, Humans, Medicine, mouse models, MESH: Animals, Molecular Biology, Genetics (clinical), Cause of death, septal defects, Fetus, MESH: Humans, Embryonic heart, Heart development, business.industry, conotruncal defects, [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis, valve defects, MESH: Heart Defects, Congenital, medicine.disease, congenital heart defects, laterality defects, [SDV.BDD.MOR] Life Sciences [q-bio]/Development Biology/Morphogenesis, MESH: Models, Animal, Models, Animal, Cardiology, business
Abstract

International audience; Congenital heart disease is the most frequent birth defect and the leading cause of death for the fetus and in the first year of life. The wide phenotypic diversity of congenital heart defects requires expert diagnosis and sophisticated repair surgery. Although these defects have been described since the seventeenth century, it was only in 2005 that a consensus international nomenclature was adopted, followed by an international classification in 2017 to help provide better management of patients. Advances in genetic engineering, imaging, and omics analyses have uncovered mechanisms of heart formation and malformation in animal models, but approximately 80% of congenital heart defects have an unknown genetic origin. Here, we summarize current knowledge of congenital structural heart defects, intertwining clinical and fundamental research perspectives, with the aim to foster interdisciplinary collaborations at the cutting edge of each field. We also discuss remaining challenges in better understanding congenital heart defects and providing benefits to patients.

Published
2021
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4. Cardiovascular events in perimembranous ventricular septal defect with left ventricular volume overload: a French prospective cohort study (FRANCISCO)

Author

Damien Bonnet, Ali Houeijeh, Gilles Bosser, Clément Karsenty, Pamela Moceri, Pauline Helms, Lisa Guirgis, Elise Barre, Quentin Hauet, Sébastien Hascoët, Khaled Hadeed, Virginie Lambert, Xavier Iriart, Nicolas Pangaud, Bérangère Urbina-Hiel, Meriem Mostefa-Kara, Charlotte Denis, Eric Hery, Zakaria Jalal, Nadir Benbrik, Pierre Mauran, Pascale Maragnes, Hugues Lucron, Pascal Amedro, Céline Gronier, Francisco investigators, Magalie Ladouceur, Stéphanie Douchin, François Godart, Bruno Lefort, Karine Warin Fresse, Jean Benoit Thambo, Maurice Guirgis, Diala Khraiche, Adeline Basquin, Daniela Laux, Ronan Bonefoy, Estibaliz Valdeolmillos, Ivan Bouzguenda, Caroline Ovaert, Antoine Legendre, Laurence Iserin, Samir Harchaoui, Laurence Cohen, Jean Marc Lupoglazoff, Bertrand Leobon, Anne-Sophie Leborgne, Carine Vastel, Aurélie Chalard, Nicolas Combes, Alban-Elouen Baruteau, Hélène Ansquer, Guy Vaksmann, Lucile Houyel, Claire Bertail, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Heart Septal Defects, Ventricular, Cardiac Catheterization, medicine.medical_specialty, Septal Occluder Device, Heart Ventricles, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Volume overload, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Ventricular outflow tract, Prospective Studies, 030212 general & internal medicine, Child, Prospective cohort study, Stroke, Heart Failure, business.industry, General Medicine, medicine.disease, Haemolysis, 3. Good health, Observational Studies as Topic, Treatment Outcome, Child, Preschool, Heart failure, Pediatrics, Perinatology and Child Health, Cardiology, Cardiology and Cardiovascular Medicine, business, Watchful waiting, Cohort study
Abstract

The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present. Background The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy. Methods The Filiale de Cardiologie Pediatrique et Congenitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018–2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed. Conclusions The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

Published
2021
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5. Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic

Author

Laurent Bonnemains, Lucile Houyel, Alice Maltret, Mehdi Oualha, Pierre Mauran, Bruno Lefort, Damien Bonnet, Mathilde Meot, Marion Grimaud, Sophie Malekzadeh-Milani, Pamela Moceri, Sylvie Falcon-Eicher, Sylvain Renolleau, Samya Abakka, Caroline Ovaert, Antoine Legendre, Sébastien Hascoët, Jean Benoit Thambo, Gilles Bosser, Johanne Auriau, Maëlle Selegny, Fanny Bajolle, Zahra Belhadjer, Maurice Beghetti, Jeanne Bordet, Julie Wacker, Diala Khraiche, Nathan Giroux, Sylvie Di Filippo, and Centre Hospitalier Universitaire de Reims (CHU Reims)

Subjects
Male, COVID-19 / virology, Stroke Volume / physiology, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Ventricular Function, Left, Ventricular Dysfunction, Left, 0302 clinical medicine, Pandemic, Severe acute respiratory syndrome coronavirus 2, Inflammation / virology, 030212 general & internal medicine, Child, Heart Failure / drug therapy, ComputingMilieux_MISCELLANEOUS, COVID-19 / complications, ddc:618, Immunoglobulins, Intravenous, Myocardial stunning, Systemic Inflammatory Response Syndrome, 3. Good health, Female, Ventricular Dysfunction, Left / drug therapy, Cardiology and Cardiovascular Medicine, Cardiomyopathies, 2019-20 coronavirus outbreak, Myocarditis, Coronavirus disease 2019 (COVID-19), Adolescent, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Context (language use), Heart failure, 03 medical and health sciences, Ventricular Function, Left / immunology, Physiology (medical), Inflammation / drug therapy, medicine, Humans, Retrospective Studies, Heart Failure, Inflammation, business.industry, Heart Failure / complications, COVID-19, Stroke Volume, Systemic Inflammatory Response Syndrome / virology, medicine.disease, Mucocutaneous Lymph Node Syndrome, Systemic Inflammatory Response Syndrome / complications, Immunoglobulins, Intravenous / therapeutic use, Immunology, Inflammation / complications, business, Mucocutaneous lymph node syndrome, Heart Failure / virology
Abstract

Background: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. Methods: Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Results: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2–16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was Conclusions: Children may experience an acute cardiac decompensation caused by severe inflammatory state after SARS-CoV-2 infection (multisystem inflammatory syndrome in children). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

Published
2020
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6. Assessing the role of multiple pregnancies in the association between tetralogy of Fallot and assisted reproductive techniques: a path-analysis approach

Author

François Goffinet, Lucile Houyel, Karim Tararbit, Nathalie Lelong, Damien Bonnet, Babak Khoshnood, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ), Chirurgie des cardiopathies congénitales, Centre chirurgical Marie Lannelongue, Centre de Référence des cardiopathies congénitales ( M3C ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], This work was supported by grants from the Agence de Biomédecine (Saint-Denis La Plaine, France) (to B.K.). The Paris Registry of Congenital Malformations received financial support from INSERM (Paris, France) and the Institut de Veille Sanitaire (Saint-Maurice, France). The EPICARD study was supported by three grants from the Ministry of Health (PHRC 2004, 2008 and 2011). Additional funding for the EPICARD study was provided by the AREMCAR Association (Association pour la Recherche et l ' Etude des Maladies Cardiovasculaires), On behalf of the EPICARD study group, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Centre de Référence des cardiopathies congénitales (M3C), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Chirurgical Marie Lannelongue (CCML), and BMC, Ed.

Subjects
Adult, medicine.medical_specialty, Assi sted, Reproductive Techniques, Assisted, Reproductive techniques, Epidemiology, medicine.medical_treatment, Population, [SDV.GEN] Life Sciences [q-bio]/Genetics, Intracytoplasmic sperm injection, Cohort Studies, Young Adult, Congenital, Pregnancy, Internal medicine, Medicine, Humans, Genetics(clinical), Pharmacology (medical), education, Genetics (clinical), Tetralogy of Fallot, Medicine(all), education.field_of_study, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Obstetrics, Research, Multiple pregnancies, Case-control study, General Medicine, medicine.disease, Endocrinology, Assisted, Case-Control Studies, Population study, Heart defects, Female, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Cohort study
Abstract

International audience; BACKGROUND: Assisted reproductive techniques (ART) are associated with a higher risk of tetralogy of Fallot (TOF) and multiple pregnancies may be associated with a higher risk of congenital anomalies. We assessed the extent to which the association between ART and risk of TOF may be mediated by the higher risk of multiple pregnancies associated with ART. METHODS: We conducted a case-control study using population-based data from the Paris Registry of Congenital Malformations for the period 1987-2009 and a cohort study of congenital heart defects (EPICARD). The study population included 395 cases of TOF and 4104 malformed controls with no known associations with ART. The analysis was based on a path-analysis model using a counterfactual approach, which allows decomposition of the total effect of ART into an indirect effect (that mediated by the association between ART and multiple pregnancies) and a direct effect. RESULTS: ART (all methods combined) were associated with a 2.6-fold higher odds of TOF after adjustment for maternal and paternal characteristics and year of birth (adjusted OR 2.6, 95%CI, 1.5-4.5). Most (79%) of the effect associated with ART was a direct effect (i.e., not mediated by multiple pregnancies), whereas 21% of the effect of ART was due to its association with multiple pregnancies (i.e., the indirect effect). In vitro fertilization with intracytoplasmic sperm injection was associated with a 3.5-fold higher odds of TOF (adjusted OR 3.5, 95%CI, 1.1-11.2); 11% of this effect was mediated through the association of ICSI with multiple pregnancies. CONCLUSIONS: By far, most of the higher risk of TOF associated with ART is a direct effect and only a small proportion of the effect may be mediated by multiple pregnancies.

Published
2014
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7. I point my heart with the tip of my fingers - Biometry for the diagnosis of congenital heart defects

Author

Ron Summers, Jean-Louis Dillenseger, Lucile Houyel, Tariq Abdulla, Jean-Marc Schleich, Jean-François Paul, 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), Research School of Systems Engineering, Loughborough University, Service de chirurgie des cardiopathies congénitales, Centre chirurgical Marie Lannelongue, Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Chirurgical Marie Lannelongue (CCML), and Dillenseger, Jean-Louis

Subjects
Anatomical structures, Biomedical Engineering, Biophysics, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, interactive landmarks design, anatomical structures position, Medicine, Point (geometry), Heart volume, Normal heart, 030304 developmental biology, Congenital heart disease, [SDV.IB] Life Sciences [q-bio]/Bioengineering, 0303 health sciences, business.industry, Orientation (computer vision), Heart anatomy, Anatomy, heart anatomy, geometrical modelling, 3. Good health, Position (obstetrics), [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, psychological phenomena and processes
Abstract

International audience; Congenital heart defects are characterized by abnormal positioning of some anatomical structures relative to a normal heart. Classically the classification of the disease or the stage of the disease is based on the measurement of the relative position of these structures by the cardiac morphologist. We propose a method in which the heart volume is acquired by a CT scanner. In this paper we present a tool which allows us to define landmarks interactively in this heart volume. These landmarks are then used to estimate some simple geometrical models of the anatomical structures and so to describe their relative position and orientation.

Published
2013
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8. A method for accurate, non-destructive diagnosis of congenital heart defects from heart specimens

Author

Jean-Marc Schleich, Tariq Abdulla, Lucile Houyel, Jean-François Paul, Ron Summers, Jean-Louis Dillenseger, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Research School of Systems Engineering, Loughborough University, Service de chirurgie des cardiopathies congénitales, Centre Chirurgical Marie Lannelongue (CCML), Dillenseger, Jean-Louis, 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), and Centre chirurgical Marie Lannelongue

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, non destructive analysis, anapathology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, congenital heart defects
Abstract

International audience; The accurate analysis of congenital heart defect (CHD) specimens is often difficult and up to now required the opening of the heart. The objective of this study is to define a non-destructive method that allows for the precise analysis of each specimen and its different cardiac components in order to improve classification of the defect and thus provide an indication of underpinning causal mechanisms. We propose a method in which the heart volume is acquired by a CT scanner. ). A new volume manipulation tool was developed to define interactively anatomical landmarks within the heart volumes. These landmarks are then used to estimate the geometrical characteristics of the heart. The relative distances and angles of these elements can be compared to the normal heart and between each specimen within a group of CHD specimens.

Published
2013

9. The risk for four specific congenital heart defects associated with assisted reproductive techniques: a population-based evaluation.: Assisted reproduction and congenital heart defects

Author

Babak Khoshnood, François Goffinet, Lucile Houyel, Karim Tararbit, Anne-Claire Thieulin, Nathalie Lelong, Damien Bonnet, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de chirurgie des cardiopathies congénitales, Centre chirurgical Marie Lannelongue, Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Agence de Biomédecine (Saint -Denis La Plaine, France), Inserm, Ministère de la Santé et l'Association pour la Recherche et l'Etude des Maladies Cardiovasculaires (AREMCAR), on behalf of the EPICARD study group, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Chirurgical Marie Lannelongue (CCML)

Subjects
Male, MESH: Registries, Reproductive techniques, Epidemiology, Transposition of Great Vessels, medicine.medical_treatment, MESH: Logistic Models, MESH: Risk Assessment, MESH : Transposition of Great Vessels, Intracytoplasmic sperm injection, Hypoplastic left heart syndrome, Cohort Studies, 0302 clinical medicine, Hypoplastic Left Heart Syndrome, Medicine, MESH: Transposition of Great Vessels, MESH : Female, Registries, 030212 general & internal medicine, MESH : Risk Assessment, MESH: Cohort Studies, Tetralogy of Fallot, education.field_of_study, 030219 obstetrics & reproductive medicine, Obstetrics, Rehabilitation, MESH: Infant, Newborn, Obstetrics and Gynecology, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Adult, MESH: Case-Control Studies, 3. Good health, MESH: Reproductive Techniques, Assisted, MESH : Hypoplastic Left Heart Syndrome, Heart defects, Female, Risk assessment, Cohort study, Adult, Heart Defects, Congenital, medicine.medical_specialty, MESH : Case-Control Studies, Reproductive Techniques, Assisted, assisted Intracytoplasmic sperm injection, MESH : Male, MESH : Chromosome Aberrations, Population, MESH : Cohort Studies, MESH: Tetralogy of Fallot, MESH : Infant, Newborn, Risk Assessment, Aortic Coarctation, Article, MESH: Hypoplastic Left Heart Syndrome, 03 medical and health sciences, MESH : Reproductive Techniques, Assisted, Humans, MESH: Chromosome Aberrations, education, MESH : Heart Defects, Congenital, Chromosome Aberrations, Gynecology, MESH: Humans, business.industry, MESH : Tetralogy of Fallot, MESH: Aortic Coarctation, MESH : Humans, Infant, Newborn, Case-control study, congenital, MESH: Adult, Odds ratio, MESH: Heart Defects, Congenital, medicine.disease, MESH: Male, Logistic Models, Reproductive Medicine, MESH : Aortic Coarctation, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, MESH : Registries, MESH : Logistic Models
Abstract

International audience; STUDY QUESTION: Are the risks of hypoplastic left heart syndrome, transposition of great arteries, tetralogy of Fallot (TOF) and coarctation of the aorta increased in infants conceived by different assisted reproductive techniques (ARTs)? STUDY ANSWER: ARTs, and particularly intracytoplasmic sperm injection (ICSI), are specifically associated with a higher risk of TOF. WHAT IS ALREADY KNOWN: ARTs are associated with an increase in the overall risk of birth defects. The risk for congenital heart defects (CHDs) associated with ARTs has been evaluated as a whole but there is limited information on the risks for specific CHDs. STUDY DESIGN, MATERIAL AND METHODS: We conducted a case-control study using population-based data from the Paris registry of congenital malformations for the period 1987-2009 and a cohort study of CHD (EPICARD) on 1583 cases of CHDs and 4104 malformed controls with no known associations with ARTs. ARTs included ovulation induction only, IVF and ICSI. RESULTS: Exposure to ARTs was significantly higher for TOF than controls (6.6 versus 3.5%, P = 0.002); this was not the case for the other three CHDs. ARTs (all methods combined) were associated with a 2.4-fold higher odds of TOF after adjustment for maternal characteristics, paternal age and year of birth [adjusted odds ratios (OR): 2.4, 95% confidence interval (CI): 1.5-3.7] with the highest risk associated with ICSI (adjusted OR: 3.0, 95% CI: 1.0-8.9). No statistically significant associations were found for the other CHDs. LIMITATIONS: Our study cannot disentangle to what extent the observed associations between the risk of TOF and ARTs are due to causal effects of ARTs and/or the underlying infertility problems of couples who conceive following ART. IMPLICATIONS: The developmental basis of the specific association between the risk of TOF and ARTs need to be further investigated.

Published
2013
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10. Progress with a Multiscale Systems Engineering Approach to Cardiac Development

Author

Ronald Summers, Tariq Abdulla, Lucile Houyel, Jean Marc Schleich, 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), Le Corre, Morgane, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, 0209 industrial biotechnology, 020901 industrial engineering & automation, General Computer Science, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Control and Systems Engineering, 020208 electrical & electronic engineering, 0202 electrical engineering, electronic engineering, information engineering, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 02 engineering and technology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract

International audience; Multiscale systems engineering provides a way to integrate models of real-world phenomena that allows a holistic understanding of component interactions at different levels of scale simultaneously. The discipline draws upon information engineering to provide ontological representations that are derived from digital libraries of terms, themselves found at distributed locations around the world. Cardiac development is well understood within discrete levels of analysis. The application of the multiscale framework gives added value by unlocking the relationships between genetic-based information at one level of analysis and the phenotype it encodes for at the cell and organ levels of abstraction. The multiscale-based relationships have begun to demonstrate new insights into normal cardiac development and conditions that give rise to congenital heart diseases such as the tetralogy of Fallot. This paper describes progress made in combining ontology-based information models and explains the importance of the role of multiscale systems engineering.

Published
2011

11. A new dynamic 3D virtual methodology for teaching the mechanics of atrial septation as seen in the human heart

Author

Robert H. Anderson, Lucile Houyel, Jean-Marc Schleich, Jean-Louis Dillenseger, Claude Almange, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-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], Service de chirurgie des cardiopathies congénitales, Centre Chirurgical Marie Lannelongue (CCML), Cardiac Unit, Institute of Child Health (UCL), University College of London [London] (UCL), 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), Centre chirurgical Marie Lannelongue, and Dillenseger, Jean-Louis

Subjects
Models, Anatomic, Histology, Time Factors, Organogenesis, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, User-Computer Interface, 0302 clinical medicine, Imaging, Three-Dimensional, atrial septation, Surveys and Questionnaires, Computer software, embryology, Humans, Learning, Computer Simulation, Heart Atria, 030304 developmental biology, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Physical development, 0303 health sciences, Science instruction, Internet, Models, Cardiovascular, Human heart, General Medicine, Embryology, computer graphics, College instruction, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Anatomy, Psychology, Comprehension, medical education, Neuroscience, Heart atrium, Pediatric cardiology, Computer-Assisted Instruction
Abstract

International audience; Learning embryology remains difficult, since it requires understanding of many complex phenomena. The temporal evolution of developmental events has classically been illustrated using cartoons, which create difficulty in linking spatial and temporal aspects, such correlation being the keystone of descriptive embryology. We synthesized the bibliographic data from recent studies of atrial septal development. On the basis of this synthesis, consensus on the stages of atrial septation as seen in the human heart has been reached by a group of experts in cardiac embryology and pediatric cardiology. This has permitted the preparation of three-dimensional (3D) computer graphic objects for the anatomical components involved in the different stages of normal human atrial septation. We have provided a virtual guide to the process of normal atrial septation, the animation providing an appreciation of the temporal and morphologic events necessary to separate the systemic and pulmonary venous returns. We have shown that our animations of normal human atrial septation increase significantly the teaching of the complex developmental processes involved, and provide a new dynamic for the process of learning. Anat Sci Ed 2:69-77, 2009. (c) 2009 American Association of Anatomists.

Published
2009
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12. Frequency and prognosis of arrhythmias after operative 'correction' of tetralogy of Fallot

Author

André Davignon, Anne Fournier, Jean-Claude Fouron, Guy Vaksmann, Lucile Houyel, Gilles R. Ducharme, Maladies Cardiovasculaires Infantiles et Congénitales, Conseil Régional Auvergne-Rhône-Alpes, parent, Institut Montpelliérain Alexander Grothendieck (IMAG), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie des cardiopathies congénitales, Centre chirurgical Marie Lannelongue, and Centre hospitalier universitaire Sainte-Justine [Montréal, Canada]

Subjects
Male, medicine.medical_specialty, Adolescent, Heart disease, Treadmill exercise, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Risk Factors, law, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Internal medicine, medicine, Cardiopulmonary bypass, Humans, cardiovascular diseases, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, Tetralogy of Fallot, medicine.diagnostic_test, business.industry, Infant, Arrhythmias, Cardiac, Prognosis, medicine.disease, 3. Good health, Child, Preschool, Phenytoin, Anesthesia, Ambulatory, Electrocardiography, Ambulatory, Exercise Test, cardiovascular system, Ventricular pressure, Cardiology, Female, Cardiology and Cardiovascular Medicine, Complication, business, Electrocardiography, Follow-Up Studies
Abstract

Two hundred twenty-four consecutive patients operated on for tetralogy of Fallot were followed from 1 to 28 years (mean 11). Mean age at surgery was 5.3 years (range 1 to 14). Postoperative right ventricular systolic pressure was 60 mm Hg in 19 of 213 patients (9%). Fourteen patients (6%) had ventricular premature complexes on surface electrocardiograms. Seventy-nine patients underwent treadmill exercise tests, and ventricular premature complexes were induced in 17 (22%). Twenty-four-hour ambulatory monitoring in 92 patients demonstrated significant ventricular arrhythmias (greater than or equal to grade 2 of the Lown classification) in 41 (45%). The frequency of ventricular arrhythmias correlated with length of follow-up and duration of cardiopulmonary bypass. No correlation was found with age at surgery, postoperative right ventricular systolic pressure and importance of conduction defects on electrocardiogram. There were no sudden or unexpected deaths during follow-up.

Published
1990
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