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4. Engraftment after autologous hematopoietic stem cell transplantation in patients mobilized with Plerixafor: A retrospective, multicenter study of a large series of patients

Author

Antelo, M. Luisa, Altuna, Ane, Gimeno, J. José, Ferreiro, J. Javier, Amunárriz, Cristina, Mateos, J. José, Zalba, Saioa, Alkorta, Aitziber, Rifón, José, Arroyo, J. Luis, Uresandi, Amaia, Moreno, J. Antonio, Nájera, M. Josefa, Pinzón, Sergio, García, Alejandro, and Vallejo, J. Carlos

Published
2021
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7. The role of TBX20 truncating variants in dilated and left ventricular non-compaction cardiomyopathy

Author

Amor-Salamanca, A, primary, Garcia-Cruz, L M, additional, Rasoul, H, additional, De Castro Campos, D, additional, Limeres, J, additional, Gimeno, J R, additional, Garcia-Pinilla, J M, additional, Basurte Elorz, M T, additional, Bilbao-Quesada, R, additional, Fuentes Canamero, M E, additional, Moldovan, O, additional, Trujillo-Quintero, J P, additional, Morris-Hey, T, additional, Savvatis, K, additional, and Ochoa, J P, additional

Published
2023
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8. A comprehensive CMR analysis improves risk stratification in left ventricular noncompaction

Author

Casas, G, primary, Rodenas, E, additional, Gonzalez-Del-Hoyo, M, additional, Barriales, R, additional, Garcia-Pavia, P, additional, Villacorta, E, additional, Zorio, E, additional, Jimenez-Jaimez, J, additional, Bayes, A, additional, Ripoll, T, additional, Gimeno, J R, additional, Guala, A, additional, Limeres, J, additional, Ferreira-Gonzalez, I, additional, and Rodriguez-Palomares, J F, additional

Published
2023
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10. Acute Myocarditis Associated With Desmosomal Gene Variants

Author

Ammirati, E, Raimondi, F, Piriou, N, Sardo Infirri, L, Mohiddin, S, Mazzanti, A, Shenoy, C, Cavallari, U, Imazio, M, Aquaro, G, Olivotto, I, Pedrotti, P, Sekhri, N, Van de Heyning, C, Broeckx, G, Peretto, G, Guttmann, O, Dellegrottaglie, S, Scatteia, A, Gentile, P, Merlo, M, Goldberg, R, Reyentovich, A, Sciamanna, C, Klaassen, S, Poller, W, Trankle, C, Abbate, A, Keren, A, Horowitz-Cederboim, S, Cadrin-Tourigny, J, Tadros, R, Annoni, G, Bonoldi, E, Toquet, C, Marteau, L, Probst, V, Trochu, J, Kissopoulou, A, Grosu, A, Kukavica, D, Trancuccio, A, Gil, C, Tini, G, Pedrazzini, M, Torchio, M, Sinagra, G, Gimeno, J, Bernasconi, D, Valsecchi, M, Klingel, K, Adler, E, Camici, P, Cooper, L, Ammirati E., Raimondi F., Piriou N., Sardo Infirri L., Mohiddin S. A., Mazzanti A., Shenoy C., Cavallari U. A., Imazio M., Aquaro G. D., Olivotto I., Pedrotti P., Sekhri N., Van de Heyning C. M., Broeckx G., Peretto G., Guttmann O., Dellegrottaglie S., Scatteia A., Gentile P., Merlo M., Goldberg R. I., Reyentovich A., Sciamanna C., Klaassen S., Poller W., Trankle C. R., Abbate A., Keren A., Horowitz-Cederboim S., Cadrin-Tourigny J., Tadros R., Annoni G. A., Bonoldi E., Toquet C., Marteau L., Probst V., Trochu J. N., Kissopoulou A., Grosu A., Kukavica D., Trancuccio A., Gil C., Tini G., Pedrazzini M., Torchio M., Sinagra G., Gimeno J. R., Bernasconi D., Valsecchi M. G., Klingel K., Adler E. D., Camici P. G., Cooper L. T., Ammirati, E, Raimondi, F, Piriou, N, Sardo Infirri, L, Mohiddin, S, Mazzanti, A, Shenoy, C, Cavallari, U, Imazio, M, Aquaro, G, Olivotto, I, Pedrotti, P, Sekhri, N, Van de Heyning, C, Broeckx, G, Peretto, G, Guttmann, O, Dellegrottaglie, S, Scatteia, A, Gentile, P, Merlo, M, Goldberg, R, Reyentovich, A, Sciamanna, C, Klaassen, S, Poller, W, Trankle, C, Abbate, A, Keren, A, Horowitz-Cederboim, S, Cadrin-Tourigny, J, Tadros, R, Annoni, G, Bonoldi, E, Toquet, C, Marteau, L, Probst, V, Trochu, J, Kissopoulou, A, Grosu, A, Kukavica, D, Trancuccio, A, Gil, C, Tini, G, Pedrazzini, M, Torchio, M, Sinagra, G, Gimeno, J, Bernasconi, D, Valsecchi, M, Klingel, K, Adler, E, Camici, P, Cooper, L, Ammirati E., Raimondi F., Piriou N., Sardo Infirri L., Mohiddin S. A., Mazzanti A., Shenoy C., Cavallari U. A., Imazio M., Aquaro G. D., Olivotto I., Pedrotti P., Sekhri N., Van de Heyning C. M., Broeckx G., Peretto G., Guttmann O., Dellegrottaglie S., Scatteia A., Gentile P., Merlo M., Goldberg R. I., Reyentovich A., Sciamanna C., Klaassen S., Poller W., Trankle C. R., Abbate A., Keren A., Horowitz-Cederboim S., Cadrin-Tourigny J., Tadros R., Annoni G. A., Bonoldi E., Toquet C., Marteau L., Probst V., Trochu J. N., Kissopoulou A., Grosu A., Kukavica D., Trancuccio A., Gil C., Tini G., Pedrazzini M., Torchio M., Sinagra G., Gimeno J. R., Bernasconi D., Valsecchi M. G., Klingel K., Adler E. D., Camici P. G., and Cooper L. T.

Abstract

Background: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. Objectives: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. Methods: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[−]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up. Results: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(−) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. Conclusions: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.

Published
2022

16. Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry

Author

Asselbergs F. W., Sammani A., Elliott P., Gimeno J. R., Tavazzi L., Tendera M., Kaski J. P., Maggioni A. P., Rubis P. P., Jurcut R., Helio T., Calo L., Sinagra G., Zdravkovic M., Olivotto I., Kavoliuniene A., Laroche C., Caforio A. L. P., Charron P., Komissarova S., Chakova N., Niyazova S., Linhart A., Kuchynka P., Palecek T., Podzimkova J., Fikrle M., Nemecek E., Bundgaard H., Tfelt-Hansen J., Theilade J., Thune J. J., Axelsson A., Mogensen J., Henriksen F., Hey T., Nielsen S. K., Videbaek L., Andreasen S., Arnsted H., Saad A., Ali M., Lommi J., Nieminennew M. S., Dubourg O., Mansencal N., Arslan M., Siam Tsieu V., Damy T., Guellich A., Guendouz S., Tissot C. M., Lamine A., Rappeneau S., Hagege A., Desnos M., Bachet A., Hamzaoui M., Isnard R., Legrand L., Maupain C., Gandjbakhch E., Kerneis M., Pruny J. -F., Bauer A., Pfeiffer B., Felix S. B., Dorr M., Kaczmarek S., Lehnert K., Pedersen A. -L., Beug D., Bruder M., Bohm M., Kindermann I., Linicus Y., Werner C., Neurath B., Schild-Ungerbuehler M., Seggewiss H., Neugebauer A., McKeown P., Muir A., McOsker J., Jardine T., Divine G., Lorenzini M., Watkinson O., Wicks E., Iqbal H., Mohiddin S., O'Mahony C., Sekri N., Carr-White G., Bueser T., Rajani R., Clack L., Damm J., Jones S., Sanchez-Vidal R., Smith M., Walters T., Wilson K., Rosmini S., Anastasakis A., Ritsatos K., Vlagkouli V., Forster T., Sepp R., Borbas J., Nagy V., Tringer A., Kakonyi K., Szabo L. A., Maleki M., Noohi Bezanjani F., Amin A., Naderi N., Parsaee M., Taghavi S., Ghadrdoost B., Jafari S., Khoshavi M., Rapezzi C., Biagini E., Corsini A., Gagliardi C., Graziosi M., Longhi S., Milandri A., Ragni L., Palmieri S., Arretini A., Castelli G., Cecchi F., Fornaro A., Tomberli B., Spirito P., Devoto E., Della Bella P., Maccabelli G., Sala S., Guarracini F., Peretto G., Russo M. G., Calabro R., Pacileo G., Limongelli G., Masarone D., Pazzanese V., Rea A., Rubino M., Tramonte S., Valente F., Caiazza M., Cirillo A., Del Giorno G., Esposito A., Gravino R., Marrazzo T., Trimarco B., Losi M. -A., Di Nardo C., Giamundo A., Musella F., Pacelli F., Scatteia A., Canciello G., Caforio A., Iliceto S., Calore C., Leoni L., Perazzolo Marra M., Rigato I., Tarantini G., Schiavo A., Testolina M., Arbustini E., Di Toro A., Giuliani L. P., Serio A., Fedele F., Frustaci A., Alfarano M., Chimenti C., Drago F., Baban A., Lanzillo C., Martino A., Uguccioni M., Zachara E., Halasz G., Re F., Carriere C., Merlo M., Ramani F., Krivickiene A., Tamuleviciute-Prasciene E., Viezelis M., Celutkiene J., Balkeviciene L., Laukyte M., Paleviciute E., Pinto Y., Wilde A., Van Der Heijden J., Van Laake L., De Jonge N., Hassink R., Kirkels J. H., Ajuluchukwu J., Olusegun-Joseph A., Ekure E., Mizia-Stec K., Czekaj A., Sikora-Puz A., Skoczynska A., Wybraniec M., Rubis P., Dziewiecka E., Wisniowska-Smialek S., Bilinska Z., Chmielewski P., Foss-Nieradko B., Michalak E., Stepien-Wojno M., Mazek B., Rocha Lopes L., Almeida A. R., Cruz I., Gomes A. C., Pereira A. R., Brito D., Madeira H., Francisco A. R., Menezes M., Moldovan O., Oliveira Guimaraes T., Silva D., Ginghina C., Mursa A., Popescu B. A., Apetrei E., Militaru S., Mircea Coman I., Frigy A., Fogarasi Z., Kocsis I., Szabo I. A., Fehervari L., Nikitin I., Resnik E., Komissarova M., Lazarev V., Shebzukhova M., Ustyuzhanin D., Blagova O., Alieva I., Kulikova V., Lutokhina Y., Pavlenko E., Varionchik N., Ristic A. D., Seferovic P. M., Veljic I., Zivkovic I., Milinkovic I., Pavlovic A., Radovanovic G., Simeunovic D., Aleksic M., Djokic J., Hinic S., Klasnja S., Mircetic K., Monserrat L., Fernandez X., Garcia-Giustiniani D., Larranaga J. M., Ortiz-Genga M., Barriales-Villa R., Martinez-Veira C., Veira E., Cequier A., Salazar-Mendiguchia J., Manito N., Gonzalez J., Fernandez-Aviles F., Medrano C., Yotti R., Cuenca S., Espinosa M. A., Mendez I., Zatarain E., Alvarez R., Garcia-Pavia P., Briceno A., Cobo-Marcos M., Dominguez F., De Teresa Galvan E., Garcia Pinilla J. M., Abdeselam-Mohamed N., Lopez-Garrido M. A., Morcillo Hidalgo L., Ortega-Jimenez M. V., Robles Mezcua A., Guijarro-Contreras A., Gomez-Garcia D., Robles-Mezcua M., Gimeno Blanes J. R., Castro F. J., Munoz Esparza C., Sabater Molina M., Sorli Garcia M., Lopez Cuenca D., Ripoll-Vera T., Alvarez J., Nunez J., Gomez Y., Sanchez Fernandez P. L., Villacorta E., Avila C., Bravo L., Diaz-Pelaez E., Gallego-Delgado M., Garcia-Cuenllas L., Plata B., Lopez-Haldon J. E., Pena Pena M. L., Cantero Perez E. M., Zorio E., Arnau M. A., Sanz J., Marques-Sulex E., University Medical Center [Utrecht], University College of London [London] (UCL), Hospital Univeristario Virgen de la Arrixaca, University Hospital of Ferrara and Maria Cecilia Hospital, Medical University of Silesia, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Chair of Medical Biochemistry, Jagiellonian University - Medical College, Chair of Medical Biochemistry, Emergency Hospital Floreasca Bucharest, Emergency Hospital Floreasca Bucharest, 8 Calea Floresca, Sector 1, 014461 Bucharest, Romania, University of Helsinki, Policlinico Casilino (Ospedale Policlinico Casilino), University of Trieste, University of Belgrade [Belgrade], Careggi University Hospital, Lithuanian University of health Sciences [Kaunas], Universita degli Studi di Padova, 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospital Clínico Universitario Virgen de la Arrixaca = University Hospital Virgen de la Arrixaca [Murcia], Medical University of Silesia (SUM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli studi di Trieste = University of Trieste, Università degli Studi di Padova = University of Padua (Unipd), 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), HAL-SU, Gestionnaire, Asselbergs, F. W., Sammani, A., Elliott, P., Gimeno, J. R., Tavazzi, L., Tendera, M., Kaski, J. P., Maggioni, A. P., Rubis, P. P., Jurcut, R., Helio, T., Calo, L., Sinagra, G., Zdravkovic, M., Olivotto, I., Kavoliuniene, A., Laroche, C., Caforio, A. L. P., Charron, P., Komissarova, S., Chakova, N., Niyazova, S., Linhart, A., Kuchynka, P., Palecek, T., Podzimkova, J., Fikrle, M., Nemecek, E., Bundgaard, H., Tfelt-Hansen, J., Theilade, J., Thune, J. J., Axelsson, A., Mogensen, J., Henriksen, F., Hey, T., Nielsen, S. K., Videbaek, L., Andreasen, S., Arnsted, H., Saad, A., Ali, M., Lommi, J., Nieminennew, M. S., Dubourg, O., Mansencal, N., Arslan, M., Siam Tsieu, V., Damy, T., Guellich, A., Guendouz, S., Tissot, C. M., Lamine, A., Rappeneau, S., Hagege, A., Desnos, M., Bachet, A., Hamzaoui, M., Isnard, R., Legrand, L., Maupain, C., Gandjbakhch, E., Kerneis, M., Pruny, J. -F., Bauer, A., Pfeiffer, B., Felix, S. B., Dorr, M., Kaczmarek, S., Lehnert, K., Pedersen, A. -L., Beug, D., Bruder, M., Bohm, M., Kindermann, I., Linicus, Y., Werner, C., Neurath, B., Schild-Ungerbuehler, M., Seggewiss, H., Neugebauer, A., Mckeown, P., Muir, A., Mcosker, J., Jardine, T., Divine, G., Lorenzini, M., Watkinson, O., Wicks, E., Iqbal, H., Mohiddin, S., O'Mahony, C., Sekri, N., Carr-White, G., Bueser, T., Rajani, R., Clack, L., Damm, J., Jones, S., Sanchez-Vidal, R., Smith, M., Walters, T., Wilson, K., Rosmini, S., Anastasakis, A., Ritsatos, K., Vlagkouli, V., Forster, T., Sepp, R., Borbas, J., Nagy, V., Tringer, A., Kakonyi, K., Szabo, L. A., Maleki, M., Noohi Bezanjani, F., Amin, A., Naderi, N., Parsaee, M., Taghavi, S., Ghadrdoost, B., Jafari, S., Khoshavi, M., Rapezzi, C., Biagini, E., Corsini, A., Gagliardi, C., Graziosi, M., Longhi, S., Milandri, A., Ragni, L., Palmieri, S., Arretini, A., Castelli, G., Cecchi, F., Fornaro, A., Tomberli, B., Spirito, P., Devoto, E., Della Bella, P., Maccabelli, G., Sala, S., Guarracini, F., Peretto, G., Russo, M. G., Calabro, R., Pacileo, G., Limongelli, G., Masarone, D., Pazzanese, V., Rea, A., Rubino, M., Tramonte, S., Valente, F., Caiazza, M., Cirillo, A., Del Giorno, G., Esposito, A., Gravino, R., Marrazzo, T., Trimarco, B., Losi, M. -A., Di Nardo, C., Giamundo, A., Musella, F., Pacelli, F., Scatteia, A., Canciello, G., Caforio, A., Iliceto, S., Calore, C., Leoni, L., Perazzolo Marra, M., Rigato, I., Tarantini, G., Schiavo, A., Testolina, M., Arbustini, E., Di Toro, A., Giuliani, L. P., Serio, A., Fedele, F., Frustaci, A., Alfarano, M., Chimenti, C., Drago, F., Baban, A., Lanzillo, C., Martino, A., Uguccioni, M., Zachara, E., Halasz, G., Re, F., Carriere, C., Merlo, M., Ramani, F., Krivickiene, A., Tamuleviciute-Prasciene, E., Viezelis, M., Celutkiene, J., Balkeviciene, L., Laukyte, M., Paleviciute, E., Pinto, Y., Wilde, A., Van Der Heijden, J., Van Laake, L., De Jonge, N., Hassink, R., Kirkels, J. H., Ajuluchukwu, J., Olusegun-Joseph, A., Ekure, E., Mizia-Stec, K., Czekaj, A., Sikora-Puz, A., Skoczynska, A., Wybraniec, M., Rubis, P., Dziewiecka, E., Wisniowska-Smialek, S., Bilinska, Z., Chmielewski, P., Foss-Nieradko, B., Michalak, E., Stepien-Wojno, M., Mazek, B., Rocha Lopes, L., Almeida, A. R., Cruz, I., Gomes, A. C., Pereira, A. R., Brito, D., Madeira, H., Francisco, A. R., Menezes, M., Moldovan, O., Oliveira Guimaraes, T., Silva, D., Ginghina, C., Mursa, A., Popescu, B. A., Apetrei, E., Militaru, S., Mircea Coman, I., Frigy, A., Fogarasi, Z., Kocsis, I., Szabo, I. A., Fehervari, L., Nikitin, I., Resnik, E., Komissarova, M., Lazarev, V., Shebzukhova, M., Ustyuzhanin, D., Blagova, O., Alieva, I., Kulikova, V., Lutokhina, Y., Pavlenko, E., Varionchik, N., Ristic, A. D., Seferovic, P. M., Veljic, I., Zivkovic, I., Milinkovic, I., Pavlovic, A., Radovanovic, G., Simeunovic, D., Aleksic, M., Djokic, J., Hinic, S., Klasnja, S., Mircetic, K., Monserrat, L., Fernandez, X., Garcia-Giustiniani, D., Larranaga, J. M., Ortiz-Genga, M., Barriales-Villa, R., Martinez-Veira, C., Veira, E., Cequier, A., Salazar-Mendiguchia, J., Manito, N., Gonzalez, J., Fernandez-Aviles, F., Medrano, C., Yotti, R., Cuenca, S., Espinosa, M. A., Mendez, I., Zatarain, E., Alvarez, R., Garcia-Pavia, P., Briceno, A., Cobo-Marcos, M., Dominguez, F., De Teresa Galvan, E., Garcia Pinilla, J. M., Abdeselam-Mohamed, N., Lopez-Garrido, M. A., Morcillo Hidalgo, L., Ortega-Jimenez, M. V., Robles Mezcua, A., Guijarro-Contreras, A., Gomez-Garcia, D., Robles-Mezcua, M., Gimeno Blanes, J. R., Castro, F. J., Munoz Esparza, C., Sabater Molina, M., Sorli Garcia, M., Lopez Cuenca, D., Ripoll-Vera, T., Alvarez, J., Nunez, J., Gomez, Y., Sanchez Fernandez, P. L., Villacorta, E., Avila, C., Bravo, L., Diaz-Pelaez, E., Gallego-Delgado, M., Garcia-Cuenllas, L., Plata, B., Lopez-Haldon, J. E., Pena Pena, M. L., Cantero Perez, E. M., Zorio, E., Arnau, M. A., Sanz, J., Marques-Sulex, E., Cardiology, ACS - Heart failure & arrhythmias, HUS Heart and Lung Center, Clinicum, Department of Medicine, Kardiologian yksikkö, Helsinki University Hospital Area, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Registrie, lcsh:Diseases of the circulatory (Cardiovascular) system, EUROBSERVATIONAL RESEARCH-PROGRAM, Dilated cardiomyopathy, Europe, Familial, Genetic, Prognosis, Sporadic, Adult, Humans, Prospective Studies, Registries, Cardiomyopathies, Cardiomyopathy, Dilated, Myocarditis, Cardiomyopathy, 030204 cardiovascular system & hematology, 0302 clinical medicine, Original Research Articles, Dilated, PILOT, Original Research Article, 030212 general & internal medicine, Prospective cohort study, Ejection fraction, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, Guideline adherence, 3. Good health, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, Prognosi, FREQUENCY, 03 medical and health sciences, Internal medicine, medicine, Cardiomyopathie, Genetic testing, business.industry, medicine.disease, Prospective Studie, lcsh:RC666-701, 3121 General medicine, internal medicine and other clinical medicine, Heart failure, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; AimsDilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non‐familial (sporadic) DCM (SDCM) across Europe.Methods and resultsPatients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P < 0.01), had less severe disease phenotype at presentation (P < 0.02), more favourable baseline cardiovascular risk profiles (P ≤ 0.007), and less medication use (P ≤ 0.042). Outcome at 1 year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25–0.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02–1.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P < 0.01) and had higher genetic yield (55% vs. 22%, P < 0.01).ConclusionsWe observed that FDCM and SDCM have significant differences at baseline but similar short‐term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non‐marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence.

Published
2021

18. Risk stratification in Arrhythmogenic Right Ventricular Cardiomyopathy: the impact of genotype on the 2019 ARVC risk calculator

Author

Protonotarios, A, primary, Barriales-Villa, R, additional, Antoniades, L, additional, Mogensen, J, additional, Garcia-Pavia, P, additional, Wahbi, K, additional, Biagini, E, additional, Anastasakis, A, additional, Tsatsopoulou, A, additional, Zorio, E, additional, Gimeno, J R, additional, Garcia-Pinilla, J M, additional, Sinagra, G, additional, Bauce, B, additional, and Elliott, P M, additional

Published
2022
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20. Influence of sex on cardiovascular outcomes in RBM20 variant carriers

Author

Cannie, D, primary, Protonotarios, A, additional, Syrris, P, additional, Sengupta, A, additional, Bilinska, Z, additional, Arana Achaga, X, additional, Barriales-Villa, R, additional, Garcia-Pavia, P, additional, Gimeno, J, additional, Merlo, M, additional, Wahbi, K, additional, Fatkin, D, additional, Mogensen, J, additional, Rasmussen, T B, additional, and Elliott, P, additional

Published
2022
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21. Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls

Author

Walsh, R, Lahrouchi, N, Tadros, R, Kyndt, F, Glinge, C, Postema, P, Amin, A, Nannenberg, E, Ware, J, Whiffin, N, Mazzarotto, F, Skoric-Milosavljevic, D, Krijger, C, Arbelo, E, Babuty, D, Barajas-Martinez, H, Beckmann, B, Bezieau, S, Bos, J, Breckpot, J, Campuzano, O, Castelletti, S, Celen, C, Clauss, S, Corveleyn, A, Crotti, L, Dagradi, F, de Asmundis, C, Denjoy, I, Dittmann, S, Ellinor, P, Ortuno, C, Giustetto, C, Gourraud, J, Hazeki, D, Horie, M, Ishikawa, T, Itoh, H, Kaneko, Y, Kanters, J, Kimoto, H, Kotta, M, Krapels, I, Kurabayashi, M, Lazarte, J, Leenhardt, A, Loeys, B, Lundin, C, Makiyama, T, Mansourati, J, Martins, R, Mazzanti, A, Morner, S, Napolitano, C, Ohkubo, K, Papadakis, M, Rudic, B, Molina, M, Sacher, F, Sahin, H, Sarquella-Brugada, G, Sebastiano, R, Sharma, S, Sheppard, M, Shimamoto, K, Shoemaker, M, Stallmeyer, B, Steinfurt, J, Tanaka, Y, Tester, D, Usuda, K, van der Zwaag, P, Van Dooren, S, Van Laer, L, Winbo, A, Winkel, B, Yamagata, K, Zumhagen, S, Volders, P, Lubitz, S, Antzelevitch, C, Platonov, P, Odening, K, Roden, D, Roberts, J, Skinner, J, Tfelt-Hansen, J, van den Berg, M, Olesen, M, Lambiase, P, Borggrefe, M, Hayashi, K, Rydberg, A, Nakajima, T, Yoshinaga, M, Saenen, J, Kaab, S, Brugada, P, Robyns, T, Giachino, D, Ackerman, M, Brugada, R, Brugada, J, Gimeno, J, Hasdemir, C, Guicheney, P, Priori, S, Schulze-Bahr, E, Makita, N, Schwartz, P, Shimizu, W, Aiba, T, Schott, J, Redon, R, Ohno, S, Probst, V, Arnaout, A, Amelot, M, Anselme, F, Billon, O, Defaye, P, Dupuis, J, Jesel, L, Laurent, G, Maury, P, Pasquie, J, Wiart, F, Behr, E, Barc, J, Bezzina, C, Walsh R., Lahrouchi N., Tadros R., Kyndt F., Glinge C., Postema P. G., Amin A. S., Nannenberg E. A., Ware J. S., Whiffin N., Mazzarotto F., Skoric-Milosavljevic D., Krijger C., Arbelo E., Babuty D., Barajas-Martinez H., Beckmann B. M., Bezieau S., Bos J. M., Breckpot J., Campuzano O., Castelletti S., Celen C., Clauss S., Corveleyn A., Crotti L., Dagradi F., de Asmundis C., Denjoy I., Dittmann S., Ellinor P. T., Ortuno C. G., Giustetto C., Gourraud J. -B., Hazeki D., Horie M., Ishikawa T., Itoh H., Kaneko Y., Kanters J. K., Kimoto H., Kotta M. -C., Krapels I. P. C., Kurabayashi M., Lazarte J., Leenhardt A., Loeys B. L., Lundin C., Makiyama T., Mansourati J., Martins R. P., Mazzanti A., Morner S., Napolitano C., Ohkubo K., Papadakis M., Rudic B., Molina M. S., Sacher F., Sahin H., Sarquella-Brugada G., Sebastiano R., Sharma S., Sheppard M. N., Shimamoto K., Shoemaker M. B., Stallmeyer B., Steinfurt J., Tanaka Y., Tester D. J., Usuda K., van der Zwaag P. A., Van Dooren S., Van Laer L., Winbo A., Winkel B. G., Yamagata K., Zumhagen S., Volders P. G. A., Lubitz S. A., Antzelevitch C., Platonov P. G., Odening K. E., Roden D. M., Roberts J. D., Skinner J. R., Tfelt-Hansen J., van den Berg M. P., Olesen M. S., Lambiase P. D., Borggrefe M., Hayashi K., Rydberg A., Nakajima T., Yoshinaga M., Saenen J. B., Kaab S., Brugada P., Robyns T., Giachino D. F., Ackerman M. J., Brugada R., Brugada J., Gimeno J. R., Hasdemir C., Guicheney P., Priori S. G., Schulze-Bahr E., Makita N., Schwartz P. J., Shimizu W., Aiba T., Schott J. -J., Redon R., Ohno S., Probst V., Arnaout A. A., Amelot M., Anselme F., Billon O., Defaye P., Dupuis J. -M., Jesel L., Laurent G., Maury P., Pasquie J. -L., Wiart F., Behr E. R., Barc J., Bezzina C. R., Walsh, R, Lahrouchi, N, Tadros, R, Kyndt, F, Glinge, C, Postema, P, Amin, A, Nannenberg, E, Ware, J, Whiffin, N, Mazzarotto, F, Skoric-Milosavljevic, D, Krijger, C, Arbelo, E, Babuty, D, Barajas-Martinez, H, Beckmann, B, Bezieau, S, Bos, J, Breckpot, J, Campuzano, O, Castelletti, S, Celen, C, Clauss, S, Corveleyn, A, Crotti, L, Dagradi, F, de Asmundis, C, Denjoy, I, Dittmann, S, Ellinor, P, Ortuno, C, Giustetto, C, Gourraud, J, Hazeki, D, Horie, M, Ishikawa, T, Itoh, H, Kaneko, Y, Kanters, J, Kimoto, H, Kotta, M, Krapels, I, Kurabayashi, M, Lazarte, J, Leenhardt, A, Loeys, B, Lundin, C, Makiyama, T, Mansourati, J, Martins, R, Mazzanti, A, Morner, S, Napolitano, C, Ohkubo, K, Papadakis, M, Rudic, B, Molina, M, Sacher, F, Sahin, H, Sarquella-Brugada, G, Sebastiano, R, Sharma, S, Sheppard, M, Shimamoto, K, Shoemaker, M, Stallmeyer, B, Steinfurt, J, Tanaka, Y, Tester, D, Usuda, K, van der Zwaag, P, Van Dooren, S, Van Laer, L, Winbo, A, Winkel, B, Yamagata, K, Zumhagen, S, Volders, P, Lubitz, S, Antzelevitch, C, Platonov, P, Odening, K, Roden, D, Roberts, J, Skinner, J, Tfelt-Hansen, J, van den Berg, M, Olesen, M, Lambiase, P, Borggrefe, M, Hayashi, K, Rydberg, A, Nakajima, T, Yoshinaga, M, Saenen, J, Kaab, S, Brugada, P, Robyns, T, Giachino, D, Ackerman, M, Brugada, R, Brugada, J, Gimeno, J, Hasdemir, C, Guicheney, P, Priori, S, Schulze-Bahr, E, Makita, N, Schwartz, P, Shimizu, W, Aiba, T, Schott, J, Redon, R, Ohno, S, Probst, V, Arnaout, A, Amelot, M, Anselme, F, Billon, O, Defaye, P, Dupuis, J, Jesel, L, Laurent, G, Maury, P, Pasquie, J, Wiart, F, Behr, E, Barc, J, Bezzina, C, Walsh R., Lahrouchi N., Tadros R., Kyndt F., Glinge C., Postema P. G., Amin A. S., Nannenberg E. A., Ware J. S., Whiffin N., Mazzarotto F., Skoric-Milosavljevic D., Krijger C., Arbelo E., Babuty D., Barajas-Martinez H., Beckmann B. M., Bezieau S., Bos J. M., Breckpot J., Campuzano O., Castelletti S., Celen C., Clauss S., Corveleyn A., Crotti L., Dagradi F., de Asmundis C., Denjoy I., Dittmann S., Ellinor P. T., Ortuno C. G., Giustetto C., Gourraud J. -B., Hazeki D., Horie M., Ishikawa T., Itoh H., Kaneko Y., Kanters J. K., Kimoto H., Kotta M. -C., Krapels I. P. C., Kurabayashi M., Lazarte J., Leenhardt A., Loeys B. L., Lundin C., Makiyama T., Mansourati J., Martins R. P., Mazzanti A., Morner S., Napolitano C., Ohkubo K., Papadakis M., Rudic B., Molina M. S., Sacher F., Sahin H., Sarquella-Brugada G., Sebastiano R., Sharma S., Sheppard M. N., Shimamoto K., Shoemaker M. B., Stallmeyer B., Steinfurt J., Tanaka Y., Tester D. J., Usuda K., van der Zwaag P. A., Van Dooren S., Van Laer L., Winbo A., Winkel B. G., Yamagata K., Zumhagen S., Volders P. G. A., Lubitz S. A., Antzelevitch C., Platonov P. G., Odening K. E., Roden D. M., Roberts J. D., Skinner J. R., Tfelt-Hansen J., van den Berg M. P., Olesen M. S., Lambiase P. D., Borggrefe M., Hayashi K., Rydberg A., Nakajima T., Yoshinaga M., Saenen J. B., Kaab S., Brugada P., Robyns T., Giachino D. F., Ackerman M. J., Brugada R., Brugada J., Gimeno J. R., Hasdemir C., Guicheney P., Priori S. G., Schulze-Bahr E., Makita N., Schwartz P. J., Shimizu W., Aiba T., Schott J. -J., Redon R., Ohno S., Probst V., Arnaout A. A., Amelot M., Anselme F., Billon O., Defaye P., Dupuis J. -M., Jesel L., Laurent G., Maury P., Pasquie J. -L., Wiart F., Behr E. R., Barc J., and Bezzina C. R.

Abstract

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes—rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10−18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10−13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. Conclusion: Large case–control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

Published
2021

22. Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

Author

Zhou, Z, Jardine, M, Li, Q, Neuen, B, Cannon, C, De Zeeuw, D, Edwards, R, Levin, A, Mahaffey, K, Perkovic, V, Neal, B, Lindley, R, Guerrero, R, Aizenberg, D, Albisu, J, Alvarisqueta, A, Bartolacci, I, Berli, M, Bordonava, A, Calella, P, Cantero, M, Cartasegna, L, Cercos, E, Coloma, G, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, C, Cusumano, A, Douthat, W, Dran, R, Farias, E, Fernandez, M, Finkelstein, H, Fragale, G, Fretes, J, Garcia, N, Gastaldi, A, Gelersztein, E, Glenny, J, Gonzalez, J, Del Carmen Gonzalez Colaso, P, Goycoa, C, Greloni, G, Guinsburg, A, Hermida, S, Juncos, L, Klyver, M, Kraft, F, Krynski, F, Lanchiotti, P, De La Fuente, R, Marchetta, N, Mele, P, Nicolai, S, Novoa, P, Orio, S, Otreras, F, Oviedo, A, Raffaele, P, Resk, J, Rista, L, Papini, N, Sala, J, Santos, J, Schiavi, L, Sessa, H, Casabella, T, Ulla, M, Valdez, M, Vallejos, A, Villarino, A, Visco, V, Wassermann, A, Zaidman, C, Cheung, N, Droste, C, Fraser, I, Johnson, D, Mah, P, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, R, Da Costa, F, Amodeo, C, Turatti, L, Bregman, R, Sanches, F, Canani, L, Chacra, A, Borges, J, Vencio, S, Da Silva Franco, R, D'Avila, D, De Souza Portes, E, De Souza, P, Deboni, L, Filho, F, Neto, B, Gomes, M, Kohara, S, Keitel, E, Saraiva, J, Lisboa, H, De Carvalho Contieri, F, Milagres, R, Junior, R, De Brito, C, Hissa, M, Sabbag, A, Noronha, I, Panarotto, D, Filho, R, Pereira, M, Saporito, W, Scotton, A, Schuch, T, De Almeida, R, Ramos, C, Felicio, J, Thome, F, Hachmann, J, Yamada, S, Hayashida, C, Petry, T, Zanella, M, Andreeva, V, Angelova, A, Dimitrov, S, Genadieva, V, Genova-Hristova, G, Hristozov, K, Kamenov, Z, Koundurdjiev, A, Lozanov, L, Margaritov, V, Nonchev, B, Rangelov, R, Shinkov, A, Temelkova, M, Velichkova, E, Yakov, A, Aggarwal, N, Aronson, R, Bajaj, H, Cherney, D, Chouinard, G, Conway, J, Cournoyer, S, Daroza, G, De Serres, S, Dube, F, Goldenberg, R, Gupta, A, Gupta, M, Henein, S, Khandwala, H, Leiter, L, Madore, F, Mc-Mahon, A, Muirhead, N, Pichette, V, Rabasa-Lhoret, R, Steele, A, Tangri, N, Torshizi, A, Woo, V, Zalunardo, N, Montenegro, M, Jorquera, J, Farina, M, Gajardo, V, Vejar, M, Chen, N, Chen, Q, Gan, S, Kong, Y, Li, D, Li, W, Li, X, Lin, H, Liu, J, Lu, W, Mao, H, Ren, Y, Song, W, Sun, J, Sun, L, Tu, P, Wang, G, Yang, J, Yin, A, Yu, X, Zhao, M, Zheng, H, Mendoza, J, Arcos, E, Avendano, J, Ruiz, J, Ortiz, L, Gonzalez, A, Triana, E, Higuera, J, Malaver, N, De Salazar, D, Rosero, R, Lozano, M, Cometa, L, Valenzuela, A, Alonso, R, Villegas, I, Yupanqui, H, Bartaskova, D, Barton, P, Belobradkova, J, Dohnalova, L, Drasnar, T, Ferkl, R, Halciakova, K, Klokocnikova, V, Kovar, R, Lastuvka, J, Lukac, M, Pesickova, S, Peterka, K, Pumprla, J, Rychlik, I, Saudek, F, Tesar, V, Valis, M, Weiner, P, Zemek, S, Alamartine, E, Borot, S, Cariou, B, Dussol, B, Fauvel, J, Gourdy, P, Klein, A, Le Meur, Y, Penfornis, A, Roussel, R, Saulnier, P, Thervet, E, Zaoui, P, Burst, V, Faghih, M, Faulmann, G, Haller, H, Jerwan-Keim, R, Maxeiner, S, Paschen, B, Plassmann, G, Rose, L, Orellana, R, Haase, F, Diaz, J, Roca, L, Arenales, J, Polo, J, Juarez, E, Csecsei, G, Csiky, B, Danos, P, Deak, L, Dudas, M, Harcsa, E, Keltai, K, Keresztesi, S, Kiss, K, Konyves, L, Major, L, Mileder, M, Molnar, M, Mucsi, J, Oroszlan, T, Ory, I, Paragh, G, Peterfai, E, Petro, G, Revesz, K, Takacs, R, Vangel, S, Vasas, S, Zsom, M, Oomman, A, Raju, S, Dewan, D, Fernando, M, Gopalakrishnan, N, Gracious, N, Alva, H, Jain, D, Keshavamurthy, C, Khullar, D, Sahay, M, Peringat, J, Prasad, N, Rao, K, Reddy, S, Melemadathil, S, Sudhakar, B, Vyasam, R, Bonadonna, R, Castellino, P, Ceriello, A, Chiovato, L, De Cosmo, S, De Nicola, L, Derosa, G, Carlo, A, Cianni, G, Frasca, G, Fuiano, G, Gambaro, G, Garibotto, G, Giorda, C, Malberti, F, Mandreoli, M, Mannucci, E, Orsi, E, Piatti, P, Santoro, D, Sasso, F, Serviddio, G, Stella, A, Trevisan, R, Veronelli, A, Zanoli, L, Akiyama, H, Aoki, H, Asano, A, Iitsuka, T, Kajiyama, S, Kashine, S, Kawada, T, Kodera, T, Kono, H, Koyama, K, Kumeda, Y, Miyauchi, S, Mizuyama, K, Niiya, T, Oishi, H, Ota, S, Sakakibara, T, Takai, M, Tomonaga, O, Tsujimoto, M, Wada, T, Wakasugi, M, Wakida, Y, Watanabe, T, Yamada, M, Yanagida, K, Yanase, T, Yumita, W, Gaupsiene, E, Kozloviene, D, Navickas, A, Urbanaviciene, E, Ghani, R, Kadir, K, Ali, N, Yusof, M, Gan, C, Ismail, M, Kong, W, Lam, S, Lee, L, Lim, S, Loh, C, Manocha, A, Ng, K, Ahmad, N, Ratnasingam, V, Shudim, S, Vengadasalam, P, Munoz, L, Salazar, M, Cruz, J, Soto, M, Ramos, J, Wong, A, Rotter, J, Escalante, T, Sosa, F, Lozano, F, Cervera, L, Baron, P, Ballesteros, C, Rangel, J, Jimenez, L, Santana, S, Flores, F, Molina, H, Ceballos, R, Del Campo Blanco, B, Franco, G, Loza, O, Rocha, C, Vera, G, Castellanos, R, Calcaneo, J, Rosano, M, Pattzi, H, Guzman, J, Joerg, I, Sanchez, S, Mijangos, J, Sanson, P, Tamayo Y Orozco, J, Chavez, E, Cepeda, A, Carrillo, L, Mesa, J, Escobedo, R, Baker, J, Noonan, P, Scott, R, Walker, R, Watson, E, Williams, M, Young, S, Abejuela, Z, Agra, J, Aquitania, G, Caringal, C, Comia, R, Santos, L, Gomez, O, Jimeno, C, Santos, F, Tan, G, Tolentino, M, Yao, C, Yap, Y, Ygpuara, M, Bijata-Bronisz, R, Hotlos, L, Januszewicz, A, Kaczmarek, B, Kaminska, A, Lazuka, L, Madej, A, Mazur, S, Mlodawska-Choluj, D, Nowicki, M, Orlowska-Kowalik, G, Popenda, G, Rewerska, B, Sowinski, D, Angelescu, L, Anghel, V, Avram, R, Busegeanu, M, Cif, A, Cosma, D, Crisan, C, Demian, L, Ferariu, I, Halmagyi, I, Hancu, N, Munteanu, M, Negru, D, Onaca, A, Petrica, L, Popa, A, Ranetti, A, Serafinceanu, C, Toarba, C, Agafyina, A, Barbarash, O, Barysheva, O, Chizhov, D, Dobronravov, V, Dreval, A, Glinkina, I, Grineva, E, Khirmanov, V, Kolmakova, E, Koroleva, T, Kvitkova, L, Marasaev, V, Mkrtumyan, A, Morugova, T, Nagibovich, G, Nagibovich, O, Nedogoda, S, Osipova, I, Raskina, T, Samoylova, Y, Sazonova, O, Shamkhalova, M, Shutemova, E, Shwartz, Y, Uriasyev, O, Vorobyev, S, Zateyshchikova, A, Zateyshshikov, D, Zykova, T, Antic, S, Djordjevic, M, Kendereski, A, Lalic, K, Lalic, N, Popovic-Radinovic, V, Babikova, J, Benusova, O, Buganova, I, Culak, J, Dzupina, A, Dzuponova, J, Fulop, P, Ilavska, A, Martinka, E, Ochodnicka, Z, Pella, D, Smatanova, I, Ahmed, F, Badat, A, Breedt, J, Distiller, L, Govender, V, Govender, R, Joshi, M, Jurgens, J, Latiff, G, Lombard, L, Mookadam, M, Ngcakani, N, Nortje, H, Oosthuizen, H, Pillay-Ramaya, L, Prozesky, H, Reddy, J, Rheeder, P, Seeber, M, Chae, D, Cho, Y, Jeong, I, Kim, S, Kim, Y, Kwon, H, Kwon, M, Lee, B, Lee, J, Lee, M, Nam, M, Oh, K, Park, C, Park, S, Yoon, K, Garcia, P, Mercadal, L, Barrios, C, Castro, F, Guldris, S, Lopez, M, De Los Rios, J, Fresnedo, G, Serrano, A, Garcia, I, Martinez, F, Gimeno, J, Mendoza, M, Marin, T, Portillo, C, Vila, M, Torres, M, Iglesias, J, Perez, J, Vera, M, Simon, M, Canonge, R, Riera, M, Madueno, F, Plaza, M, Chang, C, Chuang, L, Hsia, T, Hsieh, C, Hwang, S, Lin, C, Lu, Y, Sheu, W, Barna, O, Bilyk, S, Botsyurko, V, Dudar, I, Fushtey, I, Godlevska, O, Golovchenko, O, Gyrina, O, Kazmirchuk, A, Kolesnyk, M, Komisarenko, I, Korzh, O, Kravchun, N, Legun, O, Mankovskyy, B, Martynyuk, L, Mostovoy, Y, Pashkovska, N, Pererva, L, Pertseva, T, Samoylov, O, Smirnov, I, Svyshchenko, Y, Tomashkevych, H, Topchii, I, Tryshchuk, N, Tseluyko, V, Vizir, V, Vlasenko, M, Zlova, T, Zub, L, Abusnana, S, Railey, M, Abouglila, K, Ainsworth, P, Ali, Z, Arutchelvam, V, Barnard, M, Bellary, S, Davies, E, Davies, M, Davies, S, Dawson, A, Kossi, M, English, P, Fraser, D, Gnudi, L, Gunstone, A, Hall, T, Hanif, W, Jackson, A, Johnson, A, Joseph, F, Krishnan, S, Kumwenda, M, Macdougall, I, Nixon, P, O'Hare, J, Philip, S, Ramtoola, S, Saxena, M, Sennik, D, Simon, G, Singh, B, Stephens, J, Strzelecka, A, Symonds, R, Turner, W, Wahba, M, Wakeling, J, Wheeler, D, Winocour, P, Abdallah, J, Abdullah, R, Abramowitz, M, Acosta, I, Aiello, J, Akright, L, Akyea-Djamson, A, Alappan, R, Alicic, R, Al-Karadsheh, A, Allison, D, Arauz-Pacheco, C, Arfeen, S, Arif, A, Arvind, M, Atray, N, Awad, A, Bakris, G, Barnhill, P, Barranco, E, Barrera, C, Beacom, M, Behara, V, Belo, D, Bentley-Lewis, R, Berenguer, R, Bermudez, L, Bernardo, M, Biscoveanu, M, Bowman-Stroud, C, Brandon, D, Brusco, O, Busch, R, Canaan, Y, Chilito, A, Christensen, T, Christiano, C, Christofides, E, Chuateco, C, Cohen, K, Cohen, R, Cohen-Stein, D, Cook, C, Coyne, D, Daboul, N, Darwish, R, Daswani, A, Deck, K, Desouza, C, Dev, D, Dhillon, M, Dua, S, Eder, F, Elosegui, A, El-Shahawy, M, Ervin, J, Esquenazi, A, Evans, J, Fishbane, S, Frias, J, Galindo-Ramos, E, Galphin, C, Ghazi, A, Gonzalez, E, Gorson, D, Gowda, A, Greco, B, Grubb, S, Gulati, R, Hammoud, J, Handelsman, S, Hartman, I, Hershon, K, Hiser, D, Hon, G, Jacob, R, Jaime, M, Jamal, A, Kaupke, C, Keightley, G, Kern, E, Khanna, R, Khitan, Z, Kopyt, N, Kovesdy, C, Krishna, G, Kropp, J, Kumar, A, Kumar, J, Kumar, N, Kusnir, J, Lane, W, Lawrence, M, Lehrner, L, Lentz, J, Levinson, D, Lewis, D, Liss, K, Maddux, 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J, Williams, S, Zaniewski-Singh, M, Zhou Z., Jardine M. 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Abstract

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect

Published
2021

23. Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

Author

Zhou Z., Jardine M. J., Li Q., Neuen B. L., Cannon C. P., De Zeeuw D., Edwards R., Levin A., Mahaffey K. W., Perkovic V., Neal B., Lindley R. I., Guerrero R. A. A., Aizenberg D., Albisu J. P., Alvarisqueta A., Bartolacci I., Berli M. A., Bordonava A., Calella P., Cantero M. C., Cartasegna L. R., Cercos E., Coloma G. C., Colombo H., Commendatore V., Cuadrado J., Cuneo C. A., Cusumano A. M., Douthat W. G., Dran R. D., Farias E., Fernandez M. F., Finkelstein H., Fragale G., Fretes J. O., Garcia N. H., Gastaldi A., Gelersztein E., Glenny J. A., Gonzalez J. P., Del Carmen Gonzalez Colaso P., Goycoa C., Greloni G. C., Guinsburg A., Hermida S., Juncos L. I., Klyver M. I., Kraft F., Krynski F., Lanchiotti P. V., De La Fuente R. A. L., Marchetta N., Mele P., Nicolai S., Novoa P. A., Orio S. I., Otreras F., Oviedo A., Raffaele P., Resk J. H., Rista L., Papini N. R., Sala J., Santos J. C., Schiavi L. B., Sessa H., Casabella T. S., Ulla M. R., Valdez M., Vallejos A., Villarino A., Visco V. E., Wassermann A., Zaidman C. J., Cheung N. W., Droste C., Fraser I., Johnson D., Mah P. M., Nicholls K., Packham D., Proietto J., Roberts A., Roger S., Tsang V., Raduan R. A., Da Costa F. A. A., Amodeo C., Turatti L. A. A., Bregman R., Sanches F. C. C., Canani L. H., Chacra A. R., Borges J. L. C., Vencio S. A. C., Da Silva Franco R. J., D'Avila D., De Souza Portes E., De Souza P., Deboni L. M., Filho F. F., Neto B. G., Gomes M., Kohara S. K., Keitel E., Saraiva J. F. K., Lisboa H. R. K., De Carvalho Contieri F. L., Milagres R., Junior R. M., De Brito C. M., Hissa M. N., Sabbag A. R. N., Noronha I., Panarotto D., Filho R. P., Pereira M. A., Saporito W., Scotton A. S., Schuch T., De Almeida R. S., Ramos C. S., Felicio J. S., Thome F., Hachmann J. C. T., Yamada S., Hayashida C. Y., Petry T. B. Z., Zanella M. T., Andreeva V., Angelova A., Dimitrov S., Genadieva V., Genova-Hristova G., Hristozov K., Kamenov Z., Koundurdjiev A., Lozanov L., Margaritov V., Nonchev B., Rangelov R., Shinkov A., Temelkova M., Velichkova E., Yakov A., Aggarwal N., Aronson R., Bajaj H., Cherney D., Chouinard G., Conway J., Cournoyer S., DaRoza G., De Serres S., Dube F., Goldenberg R., Gupta A., Gupta M., Henein S., Khandwala H., Leiter L., Madore F., Mc-Mahon A., Muirhead N., Pichette V., Rabasa-Lhoret R., Steele A., Tangri N., Torshizi A., Woo V., Zalunardo N., Montenegro M. A. F., Jorquera J. G. G., Farina M. M., Gajardo V. S., Vejar M., Chen N., Chen Q., Gan S., Kong Y., Li D., Li W., Li X., Lin H., Liu J., Lu W., Mao H., Ren Y., Song W., Sun J., Sun L., Tu P., Wang G., Yang J., Yin A., Yu X., Zhao M., Zheng H., Mendoza J. L. A., Arcos E., Avendano J., Ruiz J. E. A. D., Ortiz L. H. G., Gonzalez A., Triana E. H., Higuera J. D., Malaver N., De Salazar D. I. M., Rosero R., Lozano M. A. T., Cometa L. V., Valenzuela A., Alonso R. D. V., Villegas I., Yupanqui H., Bartaskova D., Barton P., Belobradkova J., Dohnalova L., Drasnar T., Ferkl R., Halciakova K., Klokocnikova V., Kovar R., Lastuvka J., Lukac M., Pesickova S., Peterka K., Pumprla J., Rychlik I., Saudek F., Tesar V., Valis M., Weiner P., Zemek S., Alamartine E., Borot S., Cariou B., Dussol B., Fauvel J. -P., Gourdy P., Klein A., Le Meur Y., Penfornis A., Roussel R., Saulnier P. -J., Thervet E., Zaoui P., Burst V., Faghih M., Faulmann G., Haller H., Jerwan-Keim R., Maxeiner S., Paschen B., Plassmann G., Rose L., Orellana R. A. G., Haase F. P., Diaz J. P. M., Roca L. A. R., Arenales J. A. S., Polo J. V. S., Juarez E. T., Csecsei G., Csiky B., Danos P., Deak L., Dudas M., Harcsa E., Keltai K., Keresztesi S., Kiss K., Konyves L., Major L., Mileder M., Molnar M., Mucsi J., Oroszlan T., Ory I., Paragh G., Peterfai E., Petro G., Revesz K., Takacs R., Vangel S., Vasas S., Zsom M., Oomman A., Raju S. B., Dewan D., Fernando M. E., Gopalakrishnan N., Gracious N., Alva H., Jain D., Keshavamurthy C. B., Khullar D., Sahay M., Peringat J., Prasad N., Rao K. S., Reddy S., Melemadathil S., Sudhakar B., Vyasam R. C., Bonadonna R., Castellino P., Ceriello A., Chiovato L., De Cosmo S., De Nicola L., Derosa G., Carlo A. D., Cianni G. D., Frasca G., Fuiano G., Gambaro G., Garibotto G., Giorda C., Malberti F., Mandreoli M., Mannucci E., Orsi E., Piatti P., Santoro D., Sasso F. C., Serviddio G., Stella A., Trevisan R., Veronelli A. M., Zanoli L., Akiyama H., Aoki H., Asano A., Iitsuka T., Kajiyama S., Kashine S., Kawada T., Kodera T., Kono H., Koyama K., Kumeda Y., Miyauchi S., Mizuyama K., Niiya T., Oishi H., Ota S., Sakakibara T., Takai M., Tomonaga O., Tsujimoto M., Wada T., Wakasugi M., Wakida Y., Watanabe T., Yamada M., Yanagida K., Yanase T., Yumita W., Gaupsiene E., Kozloviene D., Navickas A., Urbanaviciene E., Ghani R. A., Kadir K. A., Ali N., Yusof M. D. C., Gan C. L., Ismail M., Kong W. Y., Lam S. W., Lee L. Y., Lim S. K., Loh C. L., Manocha A. B., Ng K. S., Ahmad N. N. F. N., Ratnasingam V., Shudim S. S. B., Vengadasalam P., Munoz L. D. A., Salazar M. A., Cruz J. B., Soto M. B., Ramos J. C., Wong A. C., Rotter J. R. C., Escalante T. D., Sosa F. E. E., Lozano F. F., Cervera L. F. F., Baron P. F., Ballesteros C. G., Rangel J. D. G., Jimenez L. E. H., Santana S. S. I., Flores F. J., Molina H. L., Ceballos R. I. L., Del Campo Blanco B. M., Franco G. M., Loza O. T. M., Rocha C. M., Vera G. O., Castellanos R. O., Calcaneo J. P., Rosano M. A. R., Pattzi H. R., Guzman J. R., Joerg I. E. R., Sanchez S. B. S., Mijangos J. H. S., Sanson P. S., Tamayo Y Orozco J. A., Chavez E. T., Cepeda A. V., Carrillo L. V., Mesa J. V., Escobedo R. Z., Baker J., Noonan P., Scott R., Walker R., Watson E., Williams M., Young S., Abejuela Z., Agra J., Aquitania G., Caringal C., Comia R. S., Santos L. D., Gomez O., Jimeno C., Santos F., Tan G., Tolentino M., Yao C., Yap Y. E., Ygpuara M. D. L., Bijata-Bronisz R., Hotlos L., Januszewicz A., Kaczmarek B., Kaminska A., Lazuka L., Madej A., Mazur S., Mlodawska-Choluj D., Nowicki M., Orlowska-Kowalik G., Popenda G., Rewerska B., Sowinski D., Angelescu L. M., Anghel V., Avram R. -I., Busegeanu M. -M., Cif A., Cosma D., Crisan C., Demian L. D., Ferariu I. E., Halmagyi I., Hancu N., Munteanu M., Negru D., Onaca A. G., Petrica L., Popa A. R., Ranetti A. -E., Serafinceanu C., Toarba C., Agafyina A., Barbarash O., Barysheva O., Chizhov D., Dobronravov V., Dreval A., Glinkina I., Grineva E., Khirmanov V., Kolmakova E., Koroleva T., Kvitkova L., Marasaev V., Mkrtumyan A., Morugova T., Nagibovich G., Nagibovich O., Nedogoda S., Osipova I., Raskina T., Samoylova Y., Sazonova O., Shamkhalova M., Shutemova E., Shwartz Y., Uriasyev O., Vorobyev S., Zateyshchikova A., Zateyshshikov D., Zykova T., Antic S., Djordjevic M., Kendereski A., Lalic K., Lalic N., Popovic-Radinovic V., Babikova J., Benusova O., Buganova I., Culak J., Dzupina A., Dzuponova J., Fulop P., Ilavska A., Martinka E., Ochodnicka Z., Pella D., Smatanova I., Ahmed F., Badat A., Breedt J., Distiller L., Govender V., Govender R., Joshi M., Jurgens J., Latiff G., Lombard L., Mookadam M., Ngcakani N., Nortje H., Oosthuizen H., Pillay-Ramaya L., Prozesky H., Reddy J., Rheeder P., Seeber M., Chae D. -W., Cho Y. M., Jeong I. -K., Kim S. G., Kim Y. H., Kwon H. -S., Kwon M. J., Lee B. -W., Lee J., Lee M. -K., Nam M. -S., Oh K. -H., Park C. -Y., Park S. -H., Yoon K. H., Garcia P. A., Mercadal L. A., Barrios C., Castro F. C., Guldris S. C., Lopez M. D., De Los Rios J. E., Fresnedo G. F., Serrano A. G., Garcia I., Martinez F. J. G., Gimeno J. E. J., Mendoza M. L., Marin T. M., Portillo C. M., Vila M. A. M., Torres M. M., Iglesias J. N., Perez J. P., Vera M. P., Perez J. M. P., Simon M. A. Q., Canonge R. S., Gonzalez A. S., Riera M. T., Madueno F. J. T., Plaza M. V., Chang C. -T., Chuang L. -M., Hsia T. -L., Hsieh C. -H., Hwang S. -J., Lin C. -C., Lu Y. -C., Sheu W. H. -H., Barna O., Bilyk S. D., Botsyurko V., Dudar I., Fushtey I., Godlevska O., Golovchenko O., Gyrina O., Kazmirchuk A., Kolesnyk M., Komisarenko I., Korzh O., Kravchun N., Legun O., Mankovskyy B., Martynyuk L., Mostovoy Y., Pashkovska N., Pererva L., Pertseva T., Samoylov O., Smirnov I., Svyshchenko Y., Tomashkevych H., Topchii I., Tryshchuk N., Tseluyko V., Vizir V., Vlasenko M., Zlova T., Zub L., Abusnana S., Railey M., Abouglila K., Ainsworth P., Ali Z., Arutchelvam V., Barnard M., Bellary S., Davies E., Davies M., Davies S., Dawson A., Kossi M. E., English P., Fraser D., Gnudi L., Gunstone A., Hall T., Hanif W., Jackson A., Johnson A., Joseph F., Krishnan S., Kumwenda M., MacDougall I., Nixon P., O'Hare J., Philip S., Ramtoola S., Saxena M., Sennik D., Simon G., Singh B., Stephens J., Strzelecka A., Symonds R., Turner W., Wahba M., Wakeling J., Wheeler D., Winocour P., Abdallah J., Abdullah R., Abramowitz M., Acosta I., Aiello J., Akright L., Akyea-Djamson A., Alappan R., Alicic R., Al-Karadsheh A., Allison D. C., Arauz-Pacheco C., Arfeen S., Arif A., Arvind M., Atray N., Awad A., Bakris G., Barnhill P., Barranco E., Barrera C., Beacom M., Behara V., Belo D., Bentley-Lewis R., Berenguer R., Bermudez L., Bernardo M., Biscoveanu M., Bowman-Stroud C., Brandon D., Brusco O., Busch R., Canaan Y., Chilito A., Christensen T., Christiano C., Christofides E., Chuateco C., Cohen K., Cohen R., Cohen-Stein D., Cook C., Coyne D., Daboul N., Darwish R., Daswani A., Deck K., Desouza C., Dev D., Dhillon M., Dua S., Eder F., Elosegui A. M., El-Shahawy M., Ervin J., Esquenazi A., Evans J., Fishbane S., Frias J., Galindo-Ramos E., Galphin C., Ghazi A., Gonzalez E., Gorson D., Gowda A., Greco B., Grubb S., Gulati R., Hammoud J., Handelsman S., Hartman I., Hershon K., Hiser D., Hon G., Jacob R., Jaime M., Jamal A., Kaupke C., Keightley G., Kern E., Khanna R., Khitan Z., Kim S., Kopyt N., Kovesdy C., Krishna G., Kropp J., Kumar A., Kumar J., Kumar N., Kusnir J., Lane W., Lawrence M., Lehrner L., Lentz J., Levinson D., Lewis D., Liss K., Maddux A., Maheshwari H., Mandayam S., Marar I., Mehta B., Middleton J., Mordujovich J., Moreda R., Moustafa M., Trenche S. M., Narayanan M., Narvarte J., Nassar T., Newman G., Nichol B., Nicol P., Nisnisan J., Nossuli A. K., Obialo C., Olelewe S., Oliver M., O'Shaughnessy A., Padron J., Pankhaniya R., Parker R., Patel D., Patel G., Patel N., Pavon H., Perez A., Perez C., Perlman A., Pettis K., Pharr W., Phillips A., Purighalla R., Quesada-Suarez L., Ranjan R., Rastogi S., Rendell M., Rich L., Robinson M., Rodriguez H., Rosas S., Saba F., Sankaram R., Sarin R., Schreiman R., Scott D., Sekkarie M., Sensenbrenner J., Shakeel M., Shanik M., Shaw S., Smith S., Solomon R., Sprague A., Spry L., Suchinda P., Sultan S., Surampudi P., Sussman S., Tan A., Terrelonge A., Thompson M., Trespalacios F., Trippe B., Trueba P., Twahirwa M., Updegrove J., Van Buren P., Vannorsdall M., Varghese F., Velasquez-Mieyer P., Ventrapragada S., Vukotic G., Wadud K., Warren M., Watson H., Watts R., Weiner D., Welker J., Welsh J., Williams S., Zaniewski-Singh M., Zhou, Z., Jardine, M. J., Li, Q., Neuen, B. L., Cannon, C. P., De Zeeuw, D., Edwards, R., Levin, A., Mahaffey, K. W., Perkovic, V., Neal, B., Lindley, R. I., Guerrero, R. A. A., Aizenberg, D., Albisu, J. P., Alvarisqueta, A., Bartolacci, I., Berli, M. A., Bordonava, A., Calella, P., Cantero, M. C., Cartasegna, L. R., Cercos, E., Coloma, G. C., Colombo, H., Commendatore, V., Cuadrado, J., Cuneo, C. A., Cusumano, A. M., Douthat, W. G., Dran, R. D., Farias, E., Fernandez, M. F., Finkelstein, H., Fragale, G., Fretes, J. O., Garcia, N. H., Gastaldi, A., Gelersztein, E., Glenny, J. A., Gonzalez, J. P., Del Carmen Gonzalez Colaso, P., Goycoa, C., Greloni, G. C., Guinsburg, A., Hermida, S., Juncos, L. I., Klyver, M. I., Kraft, F., Krynski, F., Lanchiotti, P. V., De La Fuente, R. A. L., Marchetta, N., Mele, P., Nicolai, S., Novoa, P. A., Orio, S. I., Otreras, F., Oviedo, A., Raffaele, P., Resk, J. H., Rista, L., Papini, N. R., Sala, J., Santos, J. C., Schiavi, L. B., Sessa, H., Casabella, T. S., Ulla, M. R., Valdez, M., Vallejos, A., Villarino, A., Visco, V. E., Wassermann, A., Zaidman, C. J., Cheung, N. W., Droste, C., Fraser, I., Johnson, D., Mah, P. M., Nicholls, K., Packham, D., Proietto, J., Roberts, A., Roger, S., Tsang, V., Raduan, R. A., Da Costa, F. A. A., Amodeo, C., Turatti, L. A. A., Bregman, R., Sanches, F. C. C., Canani, L. H., Chacra, A. R., Borges, J. L. C., Vencio, S. A. C., Da Silva Franco, R. J., D'Avila, D., De Souza Portes, E., De Souza, P., Deboni, L. M., Filho, F. F., Neto, B. G., Gomes, M., Kohara, S. K., Keitel, E., Saraiva, J. F. K., Lisboa, H. R. K., De Carvalho Contieri, F. L., Milagres, R., Junior, R. M., De Brito, C. M., Hissa, M. N., Sabbag, A. R. N., Noronha, I., Panarotto, D., Filho, R. P., Pereira, M. A., Saporito, W., Scotton, A. S., Schuch, T., De Almeida, R. S., Ramos, C. S., Felicio, J. S., Thome, F., Hachmann, J. C. T., Yamada, S., Hayashida, C. Y., Petry, T. B. Z., Zanella, M. T., Andreeva, V., Angelova, A., Dimitrov, S., Genadieva, V., Genova-Hristova, G., Hristozov, K., Kamenov, Z., Koundurdjiev, A., Lozanov, L., Margaritov, V., Nonchev, B., Rangelov, R., Shinkov, A., Temelkova, M., Velichkova, E., Yakov, A., Aggarwal, N., Aronson, R., Bajaj, H., Cherney, D., Chouinard, G., Conway, J., Cournoyer, S., Daroza, G., De Serres, S., Dube, F., Goldenberg, R., Gupta, A., Gupta, M., Henein, S., Khandwala, H., Leiter, L., Madore, F., Mc-Mahon, A., Muirhead, N., Pichette, V., Rabasa-Lhoret, R., Steele, A., Tangri, N., Torshizi, A., Woo, V., Zalunardo, N., Montenegro, M. A. F., Jorquera, J. G. G., Farina, M. M., Gajardo, V. S., Vejar, M., Chen, N., Chen, Q., Gan, S., Kong, Y., Li, D., Li, W., Li, X., Lin, H., Liu, J., Lu, W., Mao, H., Ren, Y., Song, W., Sun, J., Sun, L., Tu, P., Wang, G., Yang, J., Yin, A., Yu, X., Zhao, M., Zheng, H., Mendoza, J. L. A., Arcos, E., Avendano, J., Ruiz, J. E. A. D., Ortiz, L. H. G., Gonzalez, A., Triana, E. H., Higuera, J. D., Malaver, N., De Salazar, D. I. M., Rosero, R., Lozano, M. A. T., Cometa, L. V., Valenzuela, A., Alonso, R. D. V., Villegas, I., Yupanqui, H., Bartaskova, D., Barton, P., Belobradkova, J., Dohnalova, L., Drasnar, T., Ferkl, R., Halciakova, K., Klokocnikova, V., Kovar, R., Lastuvka, J., Lukac, M., Pesickova, S., Peterka, K., Pumprla, J., Rychlik, I., Saudek, F., Tesar, V., Valis, M., Weiner, P., Zemek, S., Alamartine, E., Borot, S., Cariou, B., Dussol, B., Fauvel, J. -P., Gourdy, P., Klein, A., Le Meur, Y., Penfornis, A., Roussel, R., Saulnier, P. -J., Thervet, E., Zaoui, P., Burst, V., Faghih, M., Faulmann, G., Haller, H., Jerwan-Keim, R., Maxeiner, S., Paschen, B., Plassmann, G., Rose, L., Orellana, R. A. G., Haase, F. P., Diaz, J. P. M., Roca, L. A. R., Arenales, J. A. S., Polo, J. V. S., Juarez, E. T., Csecsei, G., Csiky, B., Danos, P., Deak, L., Dudas, M., Harcsa, E., Keltai, K., Keresztesi, S., Kiss, K., Konyves, L., Major, L., Mileder, M., Molnar, M., Mucsi, J., Oroszlan, T., Ory, I., Paragh, G., Peterfai, E., Petro, G., Revesz, K., Takacs, R., Vangel, S., Vasas, S., Zsom, M., Oomman, A., Raju, S. B., Dewan, D., Fernando, M. E., Gopalakrishnan, N., Gracious, N., Alva, H., Jain, D., Keshavamurthy, C. B., Khullar, D., Sahay, M., Peringat, J., Prasad, N., Rao, K. S., Reddy, S., Melemadathil, S., Sudhakar, B., Vyasam, R. C., Bonadonna, R., Castellino, P., Ceriello, A., Chiovato, L., De Cosmo, S., De Nicola, L., Derosa, G., Carlo, A. D., Cianni, G. D., Frasca, G., Fuiano, G., Gambaro, G., Garibotto, G., Giorda, C., Malberti, F., Mandreoli, M., Mannucci, E., Orsi, E., Piatti, P., Santoro, D., Sasso, F. C., Serviddio, G., Stella, A., Trevisan, R., Veronelli, A. M., Zanoli, L., Akiyama, H., Aoki, H., Asano, A., Iitsuka, T., Kajiyama, S., Kashine, S., Kawada, T., Kodera, T., Kono, H., Koyama, K., Kumeda, Y., Miyauchi, S., Mizuyama, K., Niiya, T., Oishi, H., Ota, S., Sakakibara, T., Takai, M., Tomonaga, O., Tsujimoto, M., Wada, T., Wakasugi, M., Wakida, Y., Watanabe, T., Yamada, M., Yanagida, K., Yanase, T., Yumita, W., Gaupsiene, E., Kozloviene, D., Navickas, A., Urbanaviciene, E., Ghani, R. A., Kadir, K. A., Ali, N., Yusof, M. D. C., Gan, C. L., Ismail, M., Kong, W. Y., Lam, S. W., Lee, L. Y., Lim, S. K., Loh, C. L., Manocha, A. B., Ng, K. S., Ahmad, N. N. F. N., Ratnasingam, V., Shudim, S. S. B., Vengadasalam, P., Munoz, L. D. A., Salazar, M. A., Cruz, J. B., Soto, M. B., Ramos, J. C., Wong, A. C., Rotter, J. R. C., Escalante, T. D., Sosa, F. E. E., Lozano, F. F., Cervera, L. F. F., Baron, P. F., Ballesteros, C. G., Rangel, J. D. G., Jimenez, L. E. H., Santana, S. S. I., Flores, F. J., Molina, H. L., Ceballos, R. I. L., Del Campo Blanco, B. M., Franco, G. M., Loza, O. T. M., Rocha, C. M., Vera, G. O., Castellanos, R. O., Calcaneo, J. P., Rosano, M. A. R., Pattzi, H. R., Guzman, J. R., Joerg, I. E. R., Sanchez, S. B. S., Mijangos, J. H. S., Sanson, P. S., Tamayo Y Orozco, J. A., Chavez, E. T., Cepeda, A. V., Carrillo, L. V., Mesa, J. V., Escobedo, R. Z., Baker, J., Noonan, P., Scott, R., Walker, R., Watson, E., Williams, M., Young, S., Abejuela, Z., Agra, J., Aquitania, G., Caringal, C., Comia, R. S., Santos, L. D., Gomez, O., Jimeno, C., Santos, F., Tan, G., Tolentino, M., Yao, C., Yap, Y. E., Ygpuara, M. D. L., Bijata-Bronisz, R., Hotlos, L., Januszewicz, A., Kaczmarek, B., Kaminska, A., Lazuka, L., Madej, A., Mazur, S., Mlodawska-Choluj, D., Nowicki, M., Orlowska-Kowalik, G., Popenda, G., Rewerska, B., Sowinski, D., Angelescu, L. M., Anghel, V., Avram, R. -I., Busegeanu, M. -M., Cif, A., Cosma, D., Crisan, C., Demian, L. D., Ferariu, I. E., Halmagyi, I., Hancu, N., Munteanu, M., Negru, D., Onaca, A. G., Petrica, L., Popa, A. R., Ranetti, A. -E., Serafinceanu, C., Toarba, C., Agafyina, A., Barbarash, O., Barysheva, O., Chizhov, D., Dobronravov, V., Dreval, A., Glinkina, I., Grineva, E., Khirmanov, V., Kolmakova, E., Koroleva, T., Kvitkova, L., Marasaev, V., Mkrtumyan, A., Morugova, T., Nagibovich, G., Nagibovich, O., Nedogoda, S., Osipova, I., Raskina, T., Samoylova, Y., Sazonova, O., Shamkhalova, M., Shutemova, E., Shwartz, Y., Uriasyev, O., Vorobyev, S., Zateyshchikova, A., Zateyshshikov, D., Zykova, T., Antic, S., Djordjevic, M., Kendereski, A., Lalic, K., Lalic, N., Popovic-Radinovic, V., Babikova, J., Benusova, O., Buganova, I., Culak, J., Dzupina, A., Dzuponova, J., Fulop, P., Ilavska, A., Martinka, E., Ochodnicka, Z., Pella, D., Smatanova, I., Ahmed, F., Badat, A., Breedt, J., Distiller, L., Govender, V., Govender, R., Joshi, M., Jurgens, J., Latiff, G., Lombard, L., Mookadam, M., Ngcakani, N., Nortje, H., Oosthuizen, H., Pillay-Ramaya, L., Prozesky, H., Reddy, J., Rheeder, P., Seeber, M., Chae, D. -W., Cho, Y. 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Subjects
medicine.medical_specialty, Original Contributions, atrial fibrillation, canagliflozin, glomerular filtration rate, hemorrhagic stroke, ischemic stroke, Renal function, Disease, Brain Ischemia, Clinical and Population Sciences, Meta-Analysis as Topic, Internal medicine, CREDENCE Trial Investigators, Atrial Fibrillation, medicine, Diabetes Mellitus, Humans, Diabetic Nephropathies, Canagliflozin, Stroke, 1102 Cardiorespiratory Medicine and Haematology, Sodium-Glucose Transporter 2 Inhibitors, Advanced and Specialized Nursing, Neurology & Neurosurgery, business.industry, Atrial fibrillation, 1103 Clinical Sciences, medicine.disease, Diabetes Mellitus, Type 2, Meta-analysis, Cardiology, Albuminuria, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, 1109 Neurosciences, Kidney disease, medicine.drug
Abstract

Supplemental Digital Content is available in the text., Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (

Published
2021

31. Author Correction: Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility (Nature Genetics, (2022), 54, 3, (232-239), 10.1038/s41588-021-01007-6)

Author

Julien Barc, Barc, J, Tadros, R, Glinge, C, Chiang, D, Jouni, M, Simonet, F, Jurgens, S, Baudic, M, Nicastro, M, Potet, F, Offerhaus, J, Walsh, R, Hoan Choi, S, Verkerk, A, Mizusawa, Y, Anys, S, Minois, D, Arnaud, M, Duchateau, J, Wijeyeratne, Y, Muir, A, Papadakis, M, Castelletti, S, Torchio, M, Gil Ortuño, C, Lacunza, J, Giachino, D, Cerrato, N, Martins, R, Campuzano, O, Van Dooren, S, Thollet, A, Kyndt, F, Mazzanti, A, Clémenty, N, Bisson, A, Corveleyn, A, Stallmeyer, B, Dittmann, S, Saenen, J, Noël, A, Honarbakhsh, S, Rudic, B, Marzak, H, Rowe, M, Federspiel, C, Le Page, S, Placide, L, Milhem, A, Barajas-Martinez, H, Beckmann, B, Krapels, I, Steinfurt, J, Gregers Winkel, B, Jabbari, R, Shoemaker, M, Boukens, B, Škorić-Milosavljević, D, Bikker, H, Manevy, F, Lichtner, P, Ribasés, M, Meitinger, T, Müller-Nurasyid, M, Group, K, Veldink, J, van den Berg, L, Van Damme, P, Cusi, D, Lanzani, C, Rigade, S, Charpentier, E, Baron, E, Bonnaud, S, Lecointe, S, Donnart, A, Le Marec, H, Chatel, S, Karakachoff, M, Bézieau, S, London, B, Tfelt-Hansen, J, Roden, D, Odening, K, Cerrone, M, Chinitz, L, Volders, P, van de Berg, M, Laurent, G, Faivre, L, Antzelevitch, C, Kääb, S, Al Arnaout, A, Dupuis, J, Pasquie, J, Billon, O, Roberts, J, Jesel, L, Borggrefe, M, Lambiase, P, Mansourati, J, Loeys, B, Leenhardt, A, Guicheney, P, Maury, P, Schulze-Bahr, E, Robyns, T, Breckpot, J, Babuty, D, Priori, S, Napolitano, C, Referral Center for inherited cardiac arrhythmia, N, de Asmundis, C, Brugada, P, Brugada, R, Arbelo, E, Brugada, J, Mabo, P, Behar, N, Giustetto, C, Sabater Molina, M, Gimeno, J, Hasdemir, C, Schwartz, P, Crotti, L, Mckeown, P, Sharma, S, Behr, E, Haissaguerre, M, Sacher, F, Rooryck, C, Tan, H, Remme, C, Postema, P, Delmar, M, Ellinor, P, Lubitz, S, Gourraud, J, Tanck, M, L. George Jr., A, Macrae, C, Burridge, P, Dina, C, Probst, V, Wilde, A, Schott, J, Redon &amp, R, Bezzina, C, Julien Barc, Rafik Tadros, Charlotte Glinge, David Y. Chiang, Mariam Jouni, Floriane Simonet, Sean J. Jurgens, Manon Baudic, Michele Nicastro, Franck Potet, Joost A. Offerhaus, Roddy Walsh, Seung Hoan Choi, Arie O. Verkerk, Yuka Mizusawa, Soraya Anys, Damien Minois, Marine Arnaud, Josselin Duchateau, Yanushi D. Wijeyeratne, Alison Muir, Michael Papadakis, Silvia Castelletti, Margherita Torchio, Cristina Gil Ortuño, Javier Lacunza, Daniela F. Giachino, Natascia Cerrato, Raphaël P. Martins, Oscar Campuzano, Sonia Van Dooren, Aurélie Thollet, Florence Kyndt, Andrea Mazzanti, Nicolas Clémenty, Arnaud Bisson, Anniek Corveleyn, Birgit Stallmeyer, Sven Dittmann, Johan Saenen, Antoine Noël, Shohreh Honarbakhsh, Boris Rudic, Halim Marzak, Matthew K. Rowe, Claire Federspiel, Sophie Le Page, Leslie Placide, Antoine Milhem, Hector Barajas-Martinez, Britt-Maria Beckmann, Ingrid P. Krapels, Johannes Steinfurt, Bo Gregers Winkel, Reza Jabbari, Moore B. Shoemaker, Bas J. Boukens, Doris Škorić-Milosavljević, Hennie Bikker, Federico Manevy, Peter Lichtner, Marta Ribasés, Thomas Meitinger, Martina Müller-Nurasyid, KORA-Study Group, Jan H. Veldink, Leonard H. van den Berg, Philip Van Damme, Daniele Cusi, Chiara Lanzani, Sidwell Rigade, Eric Charpentier, Estelle Baron, Stéphanie Bonnaud, Simon Lecointe, Audrey Donnart, Hervé Le Marec, Stéphanie Chatel, Matilde Karakachoff, Stéphane Bézieau, Barry London, Jacob Tfelt-Hansen, Dan Roden, Katja E. Odening, Marina Cerrone, Larry A. Chinitz, Paul G. Volders, Maarten P. van de Berg, Gabriel Laurent, Laurence Faivre, Charles Antzelevitch, Stefan Kääb, Alain Al Arnaout, Jean-Marc Dupuis, Jean-Luc Pasquie, Olivier Billon, Jason D. Roberts, Laurence Jesel, Martin Borggrefe, Pier D. Lambiase, Jacques Mansourati, Bart Loeys, Antoine Leenhardt, Pascale Guicheney, Philippe Maury, Eric Schulze-Bahr, Tomas Robyns, Jeroen Breckpot, Dominique Babuty, Silvia G. Priori, Carlo Napolitano, Nantes Referral Center for inherited cardiac arrhythmia, Carlo de Asmundis, Pedro Brugada, Ramon Brugada, Elena Arbelo, Josep Brugada, Philippe Mabo, Nathalie Behar, Carla Giustetto, Maria Sabater Molina, Juan R. Gimeno, Can Hasdemir, Peter J. Schwartz, Lia Crotti, Pascal P. McKeown, Sanjay Sharma, Elijah R. Behr, Michel Haissaguerre, Frédéric Sacher, Caroline Rooryck, Hanno L. Tan, Carol A. Remme, Pieter G. Postema, Mario Delmar, Patrick T. Ellinor, Steven A. Lubitz, Jean-Baptiste Gourraud, Michael W. Tanck, Alfred L. George Jr., Calum A. MacRae, Paul W. Burridge, Christian Dina, Vincent Probst, Arthur A. Wilde, Jean-Jacques Schott, Richard Redon &, Connie R. Bezzina, Julien Barc, Barc, J, Tadros, R, Glinge, C, Chiang, D, Jouni, M, Simonet, F, Jurgens, S, Baudic, M, Nicastro, M, Potet, F, Offerhaus, J, Walsh, R, Hoan Choi, S, Verkerk, A, Mizusawa, Y, Anys, S, Minois, D, Arnaud, M, Duchateau, J, Wijeyeratne, Y, Muir, A, Papadakis, M, Castelletti, S, Torchio, M, Gil Ortuño, C, Lacunza, J, Giachino, D, Cerrato, N, Martins, R, Campuzano, O, Van Dooren, S, Thollet, A, Kyndt, F, Mazzanti, A, Clémenty, N, Bisson, A, Corveleyn, A, Stallmeyer, B, Dittmann, S, Saenen, J, Noël, A, Honarbakhsh, S, Rudic, B, Marzak, H, Rowe, M, Federspiel, C, Le Page, S, Placide, L, Milhem, A, Barajas-Martinez, H, Beckmann, B, Krapels, I, Steinfurt, J, Gregers Winkel, B, Jabbari, R, Shoemaker, M, Boukens, B, Škorić-Milosavljević, D, Bikker, H, Manevy, F, Lichtner, P, Ribasés, M, Meitinger, T, Müller-Nurasyid, M, Group, K, Veldink, J, van den Berg, L, Van Damme, P, Cusi, D, Lanzani, C, Rigade, S, Charpentier, E, Baron, E, Bonnaud, S, Lecointe, S, Donnart, A, Le Marec, H, Chatel, S, Karakachoff, M, Bézieau, S, London, B, Tfelt-Hansen, J, Roden, D, Odening, K, Cerrone, M, Chinitz, L, Volders, P, van de Berg, M, Laurent, G, Faivre, L, Antzelevitch, C, Kääb, S, Al Arnaout, A, Dupuis, J, Pasquie, J, Billon, O, Roberts, J, Jesel, L, Borggrefe, M, Lambiase, P, Mansourati, J, Loeys, B, Leenhardt, A, Guicheney, P, Maury, P, Schulze-Bahr, E, Robyns, T, Breckpot, J, Babuty, D, Priori, S, Napolitano, C, Referral Center for inherited cardiac arrhythmia, N, de Asmundis, C, Brugada, P, Brugada, R, Arbelo, E, Brugada, J, Mabo, P, Behar, N, Giustetto, C, Sabater Molina, M, Gimeno, J, Hasdemir, C, Schwartz, P, Crotti, L, Mckeown, P, Sharma, S, Behr, E, Haissaguerre, M, Sacher, F, Rooryck, C, Tan, H, Remme, C, Postema, P, Delmar, M, Ellinor, P, Lubitz, S, Gourraud, J, Tanck, M, L. George Jr., A, Macrae, C, Burridge, P, Dina, C, Probst, V, Wilde, A, Schott, J, Redon &amp, R, Bezzina, C, Julien Barc, Rafik Tadros, Charlotte Glinge, David Y. Chiang, Mariam Jouni, Floriane Simonet, Sean J. Jurgens, Manon Baudic, Michele Nicastro, Franck Potet, Joost A. Offerhaus, Roddy Walsh, Seung Hoan Choi, Arie O. Verkerk, Yuka Mizusawa, Soraya Anys, Damien Minois, Marine Arnaud, Josselin Duchateau, Yanushi D. Wijeyeratne, Alison Muir, Michael Papadakis, Silvia Castelletti, Margherita Torchio, Cristina Gil Ortuño, Javier Lacunza, Daniela F. Giachino, Natascia Cerrato, Raphaël P. Martins, Oscar Campuzano, Sonia Van Dooren, Aurélie Thollet, Florence Kyndt, Andrea Mazzanti, Nicolas Clémenty, Arnaud Bisson, Anniek Corveleyn, Birgit Stallmeyer, Sven Dittmann, Johan Saenen, Antoine Noël, Shohreh Honarbakhsh, Boris Rudic, Halim Marzak, Matthew K. Rowe, Claire Federspiel, Sophie Le Page, Leslie Placide, Antoine Milhem, Hector Barajas-Martinez, Britt-Maria Beckmann, Ingrid P. Krapels, Johannes Steinfurt, Bo Gregers Winkel, Reza Jabbari, Moore B. Shoemaker, Bas J. Boukens, Doris Škorić-Milosavljević, Hennie Bikker, Federico Manevy, Peter Lichtner, Marta Ribasés, Thomas Meitinger, Martina Müller-Nurasyid, KORA-Study Group, Jan H. Veldink, Leonard H. van den Berg, Philip Van Damme, Daniele Cusi, Chiara Lanzani, Sidwell Rigade, Eric Charpentier, Estelle Baron, Stéphanie Bonnaud, Simon Lecointe, Audrey Donnart, Hervé Le Marec, Stéphanie Chatel, Matilde Karakachoff, Stéphane Bézieau, Barry London, Jacob Tfelt-Hansen, Dan Roden, Katja E. Odening, Marina Cerrone, Larry A. Chinitz, Paul G. Volders, Maarten P. van de Berg, Gabriel Laurent, Laurence Faivre, Charles Antzelevitch, Stefan Kääb, Alain Al Arnaout, Jean-Marc Dupuis, Jean-Luc Pasquie, Olivier Billon, Jason D. Roberts, Laurence Jesel, Martin Borggrefe, Pier D. Lambiase, Jacques Mansourati, Bart Loeys, Antoine Leenhardt, Pascale Guicheney, Philippe Maury, Eric Schulze-Bahr, Tomas Robyns, Jeroen Breckpot, Dominique Babuty, Silvia G. Priori, Carlo Napolitano, Nantes Referral Center for inherited cardiac arrhythmia, Carlo de Asmundis, Pedro Brugada, Ramon Brugada, Elena Arbelo, Josep Brugada, Philippe Mabo, Nathalie Behar, Carla Giustetto, Maria Sabater Molina, Juan R. Gimeno, Can Hasdemir, Peter J. Schwartz, Lia Crotti, Pascal P. McKeown, Sanjay Sharma, Elijah R. Behr, Michel Haissaguerre, Frédéric Sacher, Caroline Rooryck, Hanno L. Tan, Carol A. Remme, Pieter G. Postema, Mario Delmar, Patrick T. Ellinor, Steven A. Lubitz, Jean-Baptiste Gourraud, Michael W. Tanck, Alfred L. George Jr., Calum A. MacRae, Paul W. Burridge, Christian Dina, Vincent Probst, Arthur A. Wilde, Jean-Jacques Schott, Richard Redon &, and Connie R. Bezzina

Abstract

In the version of this article initially published, Federico Manevy’s name appeared with a middle initial in error. The name has been corrected in the HTML and PDF versions of the article.

Published
2022

32. Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Author

Barc, J, Tadros, R, Glinge, C, Chiang, D, Jouni, M, Simonet, F, Jurgens, S, Baudic, M, Nicastro, M, Potet, F, Offerhaus, J, Walsh, R, Hoan Choi, S, Verkerk, A, Mizusawa, Y, Anys, S, Minois, D, Arnaud, M, Duchateau, J, Wijeyeratne, Y, Muir, A, Papadakis, M, Castelletti, S, Torchio, M, Gil Ortuño, C, Lacunza, J, Giachino, D, Cerrato, N, Martins, R, Campuzano, O, Van Dooren, S, Thollet, A, Kyndt, F, Mazzanti, A, Clémenty, N, Bisson, A, Corveleyn, A, Stallmeyer, B, Dittmann, S, Saenen, J, Noël, A, Honarbakhsh, S, Rudic, B, Marzak, H, Rowe, M, Federspiel, C, Le Page, S, Placide, L, Milhem, A, Barajas-Martinez, H, Beckmann, B, Krapels, I, Steinfurt, J, Gregers Winkel, B, Jabbari, R, Shoemaker, M, Boukens, B, Škorić-Milosavljević, D, Bikker, H, Manevy, F, Lichtner, P, Ribasés, M, Meitinger, T, Müller-Nurasyid, M, Group, K, Veldink, J, van den Berg, L, Van Damme, P, Cusi, D, Lanzani, C, Rigade, S, Charpentier, E, Baron, E, Bonnaud, S, Lecointe, S, Donnart, A, Le Marec, H, Chatel, S, Karakachoff, M, Bézieau, S, London, B, Tfelt-Hansen, J, Roden, D, Odening, K, Cerrone, M, Chinitz, L, Volders, P, van de Berg, M, Laurent, G, Faivre, L, Antzelevitch, C, Kääb, S, Al Arnaout, A, Dupuis, J, Pasquie, J, Billon, O, Roberts, J, Jesel, L, Borggrefe, M, Lambiase, P, Mansourati, J, Loeys, B, Leenhardt, A, Guicheney, P, Maury, P, Schulze-Bahr, E, Robyns, T, Breckpot, J, Babuty, D, Priori, S, Napolitano, C, Referral Center for inherited cardiac arrhythmia, N, de Asmundis, C, Brugada, P, Brugada, R, Arbelo, E, Brugada, J, Mabo, P, Behar, N, Giustetto, C, Sabater Molina, M, Gimeno, J, Hasdemir, C, Schwartz, P, Crotti, L, Mckeown, P, Sharma, S, Behr, E, Haissaguerre, M, Sacher, F, Rooryck, C, Tan, H, Remme, C, Postema, P, Delmar, M, Ellinor, P, Lubitz, S, Gourraud, J, Tanck, M, L. George Jr., A, Macrae, C, Burridge, P, Dina, C, Probst, V, Wilde, A, Schott, J, Redon &amp, R, Bezzina, C, Julien Barc, Rafik Tadros, Charlotte Glinge, David Y. Chiang, Mariam Jouni, Floriane Simonet, Sean J. Jurgens, Manon Baudic, Michele Nicastro, Franck Potet, Joost A. Offerhaus, Roddy Walsh, Seung Hoan Choi, Arie O. Verkerk, Yuka Mizusawa, Soraya Anys, Damien Minois, Marine Arnaud, Josselin Duchateau, Yanushi D. Wijeyeratne, Alison Muir, Michael Papadakis, Silvia Castelletti, Margherita Torchio, Cristina Gil Ortuño, Javier Lacunza, Daniela F. Giachino, Natascia Cerrato, Raphaël P. Martins, Oscar Campuzano, Sonia Van Dooren, Aurélie Thollet, Florence Kyndt, Andrea Mazzanti, Nicolas Clémenty, Arnaud Bisson, Anniek Corveleyn, Birgit Stallmeyer, Sven Dittmann, Johan Saenen, Antoine Noël, Shohreh Honarbakhsh, Boris Rudic, Halim Marzak, Matthew K. Rowe, Claire Federspiel, Sophie Le Page, Leslie Placide, Antoine Milhem, Hector Barajas-Martinez, Britt-Maria Beckmann, Ingrid P. Krapels, Johannes Steinfurt, Bo Gregers Winkel, Reza Jabbari, Moore B. Shoemaker, Bas J. Boukens, Doris Škorić-Milosavljević, Hennie Bikker, Federico Manevy, Peter Lichtner, Marta Ribasés, Thomas Meitinger, Martina Müller-Nurasyid, KORA-Study Group, Jan H. Veldink, Leonard H. van den Berg, Philip Van Damme, Daniele Cusi, Chiara Lanzani, Sidwell Rigade, Eric Charpentier, Estelle Baron, Stéphanie Bonnaud, Simon Lecointe, Audrey Donnart, Hervé Le Marec, Stéphanie Chatel, Matilde Karakachoff, Stéphane Bézieau, Barry London, Jacob Tfelt-Hansen, Dan Roden, Katja E. Odening, Marina Cerrone, Larry A. Chinitz, Paul G. Volders, Maarten P. van de Berg, Gabriel Laurent, Laurence Faivre, Charles Antzelevitch, Stefan Kääb, Alain Al Arnaout, Jean-Marc Dupuis, Jean-Luc Pasquie, Olivier Billon, Jason D. Roberts, Laurence Jesel, Martin Borggrefe, Pier D. Lambiase, Jacques Mansourati, Bart Loeys, Antoine Leenhardt, Pascale Guicheney, Philippe Maury, Eric Schulze-Bahr, Tomas Robyns, Jeroen Breckpot, Dominique Babuty, Silvia G. Priori, Carlo Napolitano, Nantes Referral Center for inherited cardiac arrhythmia, Carlo de Asmundis, Pedro Brugada, Ramon Brugada, Elena Arbelo, Josep Brugada, Philippe Mabo, Nathalie Behar, Carla Giustetto, Maria Sabater Molina, Juan R. Gimeno, Can Hasdemir, Peter J. Schwartz, Lia Crotti, Pascal P. McKeown, Sanjay Sharma, Elijah R. Behr, Michel Haissaguerre, Frédéric Sacher, Caroline Rooryck, Hanno L. Tan, Carol A. Remme, Pieter G. Postema, Mario Delmar, Patrick T. Ellinor, Steven A. Lubitz, Jean-Baptiste Gourraud, Michael W. Tanck, Alfred L. George Jr., Calum A. MacRae, Paul W. Burridge, Christian Dina, Vincent Probst, Arthur A. Wilde, Jean-Jacques Schott, Richard Redon &, Connie R. Bezzina, Barc, J, Tadros, R, Glinge, C, Chiang, D, Jouni, M, Simonet, F, Jurgens, S, Baudic, M, Nicastro, M, Potet, F, Offerhaus, J, Walsh, R, Hoan Choi, S, Verkerk, A, Mizusawa, Y, Anys, S, Minois, D, Arnaud, M, Duchateau, J, Wijeyeratne, Y, Muir, A, Papadakis, M, Castelletti, S, Torchio, M, Gil Ortuño, C, Lacunza, J, Giachino, D, Cerrato, N, Martins, R, Campuzano, O, Van Dooren, S, Thollet, A, Kyndt, F, Mazzanti, A, Clémenty, N, Bisson, A, Corveleyn, A, Stallmeyer, B, Dittmann, S, Saenen, J, Noël, A, Honarbakhsh, S, Rudic, B, Marzak, H, Rowe, M, Federspiel, C, Le Page, S, Placide, L, Milhem, A, Barajas-Martinez, H, Beckmann, B, Krapels, I, Steinfurt, J, Gregers Winkel, B, Jabbari, R, Shoemaker, M, Boukens, B, Škorić-Milosavljević, D, Bikker, H, Manevy, F, Lichtner, P, Ribasés, M, Meitinger, T, Müller-Nurasyid, M, Group, K, Veldink, J, van den Berg, L, Van Damme, P, Cusi, D, Lanzani, C, Rigade, S, Charpentier, E, Baron, E, Bonnaud, S, Lecointe, S, Donnart, A, Le Marec, H, Chatel, S, Karakachoff, M, Bézieau, S, London, B, Tfelt-Hansen, J, Roden, D, Odening, K, Cerrone, M, Chinitz, L, Volders, P, van de Berg, M, Laurent, G, Faivre, L, Antzelevitch, C, Kääb, S, Al Arnaout, A, Dupuis, J, Pasquie, J, Billon, O, Roberts, J, Jesel, L, Borggrefe, M, Lambiase, P, Mansourati, J, Loeys, B, Leenhardt, A, Guicheney, P, Maury, P, Schulze-Bahr, E, Robyns, T, Breckpot, J, Babuty, D, Priori, S, Napolitano, C, Referral Center for inherited cardiac arrhythmia, N, de Asmundis, C, Brugada, P, Brugada, R, Arbelo, E, Brugada, J, Mabo, P, Behar, N, Giustetto, C, Sabater Molina, M, Gimeno, J, Hasdemir, C, Schwartz, P, Crotti, L, Mckeown, P, Sharma, S, Behr, E, Haissaguerre, M, Sacher, F, Rooryck, C, Tan, H, Remme, C, Postema, P, Delmar, M, Ellinor, P, Lubitz, S, Gourraud, J, Tanck, M, L. George Jr., A, Macrae, C, Burridge, P, Dina, C, Probst, V, Wilde, A, Schott, J, Redon &amp, R, Bezzina, C, Julien Barc, Rafik Tadros, Charlotte Glinge, David Y. Chiang, Mariam Jouni, Floriane Simonet, Sean J. Jurgens, Manon Baudic, Michele Nicastro, Franck Potet, Joost A. Offerhaus, Roddy Walsh, Seung Hoan Choi, Arie O. Verkerk, Yuka Mizusawa, Soraya Anys, Damien Minois, Marine Arnaud, Josselin Duchateau, Yanushi D. Wijeyeratne, Alison Muir, Michael Papadakis, Silvia Castelletti, Margherita Torchio, Cristina Gil Ortuño, Javier Lacunza, Daniela F. Giachino, Natascia Cerrato, Raphaël P. Martins, Oscar Campuzano, Sonia Van Dooren, Aurélie Thollet, Florence Kyndt, Andrea Mazzanti, Nicolas Clémenty, Arnaud Bisson, Anniek Corveleyn, Birgit Stallmeyer, Sven Dittmann, Johan Saenen, Antoine Noël, Shohreh Honarbakhsh, Boris Rudic, Halim Marzak, Matthew K. Rowe, Claire Federspiel, Sophie Le Page, Leslie Placide, Antoine Milhem, Hector Barajas-Martinez, Britt-Maria Beckmann, Ingrid P. Krapels, Johannes Steinfurt, Bo Gregers Winkel, Reza Jabbari, Moore B. Shoemaker, Bas J. Boukens, Doris Škorić-Milosavljević, Hennie Bikker, Federico Manevy, Peter Lichtner, Marta Ribasés, Thomas Meitinger, Martina Müller-Nurasyid, KORA-Study Group, Jan H. Veldink, Leonard H. van den Berg, Philip Van Damme, Daniele Cusi, Chiara Lanzani, Sidwell Rigade, Eric Charpentier, Estelle Baron, Stéphanie Bonnaud, Simon Lecointe, Audrey Donnart, Hervé Le Marec, Stéphanie Chatel, Matilde Karakachoff, Stéphane Bézieau, Barry London, Jacob Tfelt-Hansen, Dan Roden, Katja E. Odening, Marina Cerrone, Larry A. Chinitz, Paul G. Volders, Maarten P. van de Berg, Gabriel Laurent, Laurence Faivre, Charles Antzelevitch, Stefan Kääb, Alain Al Arnaout, Jean-Marc Dupuis, Jean-Luc Pasquie, Olivier Billon, Jason D. Roberts, Laurence Jesel, Martin Borggrefe, Pier D. Lambiase, Jacques Mansourati, Bart Loeys, Antoine Leenhardt, Pascale Guicheney, Philippe Maury, Eric Schulze-Bahr, Tomas Robyns, Jeroen Breckpot, Dominique Babuty, Silvia G. Priori, Carlo Napolitano, Nantes Referral Center for inherited cardiac arrhythmia, Carlo de Asmundis, Pedro Brugada, Ramon Brugada, Elena Arbelo, Josep Brugada, Philippe Mabo, Nathalie Behar, Carla Giustetto, Maria Sabater Molina, Juan R. Gimeno, Can Hasdemir, Peter J. Schwartz, Lia Crotti, Pascal P. McKeown, Sanjay Sharma, Elijah R. Behr, Michel Haissaguerre, Frédéric Sacher, Caroline Rooryck, Hanno L. Tan, Carol A. Remme, Pieter G. Postema, Mario Delmar, Patrick T. Ellinor, Steven A. Lubitz, Jean-Baptiste Gourraud, Michael W. Tanck, Alfred L. George Jr., Calum A. MacRae, Paul W. Burridge, Christian Dina, Vincent Probst, Arthur A. Wilde, Jean-Jacques Schott, Richard Redon &, and Connie R. Bezzina

Abstract

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.

Published
2022

37. El Plan de Orientación Universitaria en la Facultad de Veterinaria de Zaragoza y los ODS

Author

Loste, A., Álvarez, I., Acín, C., Alejandre, J. L., Arruebo, M. P., Bonastre, C., Borobia, M., Cebrián, G., García, J., García de Castro, M., Gimeno, J., Gómez, P., Gracia, L., Leciñena, P., López, P., López, R., Lorán, S., Luño, V., Martínez, F., Miana, F. J., Miranda de la Lama, G. C., Mitjana, O., Olucha, R., Pagán, R., Peribáñez, M. A., Sánchez, A. C., and Torijano, C.

Published
2022

50. La educacion permanente del maestro (Continuing Teacher Education).

Author

Ministerio de Cultura y Educacion, Buenos Aires (Argentina). Centro National de Documentacion e Informacion Educativa. and Blat, Gimeno J.

Abstract

This article discusses the importance of continuing education for teachers and various aspects of the problem which should be considered. The role and function of the teacher is discussed; continuing education must assist in developing the teacher's ability to fulfill that role. The ever-changing demands on the teacher mean that the teacher's pedagogical training must also be constantly changing. (VM)

Published
1971

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