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1. Clinical Management of Brugada Syndrome: Commentary From the Experts

Author

Cutler, M, Eckhardt, L, Kaufman, E, Arbelo, E, Behr, E, Brugada, P, Cerrone, M, Crotti, L, Deasmundis, C, Gollob, M, Horie, M, Huang, D, Krahn, A, London, B, Lubitz, S, Mackall, J, Nademanee, K, Perez, M, Probst, V, Roden, D, Sacher, F, Sarquella-Brugada, G, Scheinman, M, Shimizu, W, Shoemaker, B, Sy, R, Watanabe, A, Wilde, A, Cutler M. J., Eckhardt L. L., Kaufman E. S., Arbelo E., Behr E. R., Brugada P., Cerrone M., Crotti L., deAsmundis C., Gollob M. H., Horie M., Huang D. T., Krahn A. D., London B., Lubitz S. A., Mackall J. A., Nademanee K., Perez M. V., Probst V., Roden D. M., Sacher F., Sarquella-Brugada G., Scheinman M. M., Shimizu W., Shoemaker B., Sy R. W., Watanabe A., Wilde A. A. M., Cutler, M, Eckhardt, L, Kaufman, E, Arbelo, E, Behr, E, Brugada, P, Cerrone, M, Crotti, L, Deasmundis, C, Gollob, M, Horie, M, Huang, D, Krahn, A, London, B, Lubitz, S, Mackall, J, Nademanee, K, Perez, M, Probst, V, Roden, D, Sacher, F, Sarquella-Brugada, G, Scheinman, M, Shimizu, W, Shoemaker, B, Sy, R, Watanabe, A, Wilde, A, Cutler M. J., Eckhardt L. L., Kaufman E. S., Arbelo E., Behr E. R., Brugada P., Cerrone M., Crotti L., deAsmundis C., Gollob M. H., Horie M., Huang D. T., Krahn A. D., London B., Lubitz S. A., Mackall J. A., Nademanee K., Perez M. V., Probst V., Roden D. M., Sacher F., Sarquella-Brugada G., Scheinman M. M., Shimizu W., Shoemaker B., Sy R. W., Watanabe A., and Wilde A. A. M.

Abstract

Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.

Published
2024

2. 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

3. 2019 ESC Guidelines for themanagement of patients with supraventricular tachycardia

Author

Brugada, J, Katritsis, D, Arbelo, E, Arribas, F, Bax, J, Blomstrom-Lundqvist, C, Calkins, H, Corrado, D, Deftereos, S, Diller, G, Gomez-Doblas, J, Gorenek, B, Grace, A, Ho, S, Kaski, J, Kuck, K, Lambiase, P, Sacher, F, Sarquella-Brugada, G, Suwalski, P, Zaza, A, De Potter, T, Sticherling, C, Aboyans, V, Basso, C, Bocchiardo, M, Budts, W, Delgado, V, Dobrev, D, Fitzsimons, D, Gevaert, S, Heidbuchel, H, Hindricks, G, Hlivak, P, Kanagaratnam, P, Katus, H, Kautzner, J, Kriebel, T, Lancellotti, P, Landmesser, U, Leclercq, C, Lewis, B, Lopatin, Y, Merkely, B, Paul, T, Pavlovic, N, Petersen, S, Petronio, A, Potpara, T, Roffi, M, Scherr, D, Shlyakhto, E, Simpson, I, Zeppenfeld, K, Windecker, S, Baigent, C, Collet, J, Dean, V, Gale, C, Grobbee, D, Halvorsen, S, Iung, B, Juni, P, Lettino, M, Mueller, C, Richter, D, Sousa-Uva, M, Touyz, R, Amara, W, Grigoryan, S, Podczeck-Schweighofer, A, Chasnoits, A, Vandekerckhove, Y, Sokolovich, S, Traykov, V, Skoric, B, Papasavvas, E, Riahi, S, Kampus, P, Parikka, H, Piot, O, Etsadashvili, K, Stellbrink, C, Manolis, A, Csanadi, Z, Gudmundsson, K, Erwin, J, Barsheshet, A, De Ponti, R, Abdrakhmanov, A, Jashari, H, Lunegova, O, Jubele, K, Refaat, M, Puodziukynas, A, Groben, L, Grosu, A, Ibtissam, F, Trines, S, Poposka, L, Haugaa, K, Kowalski, O, Cavaco, D, Dobreanu, D, Mikhaylov, E, Zavatta, M, Nebojsa, M, Ferreira-Gonzalez, I, Juhlin, T, Reichlin, T, Haouala, H, Akgun, T, Gupta, D, Brugada J., Katritsis D. G., Arbelo E., Arribas F., Bax J. J., Blomstrom-Lundqvist C., Calkins H., Corrado D., Deftereos S. G., Diller G. -P., Gomez-Doblas J. J., Gorenek B., Grace A., Ho S. Y., Kaski J. -C., Kuck K. -H., Lambiase P. D., Sacher F., Sarquella-Brugada G., Suwalski P., Zaza A., De Potter T., Sticherling C., Aboyans V., Basso C., Bocchiardo M., Budts W., Delgado V., Dobrev D., Fitzsimons D., Gevaert S., Heidbuchel H., Hindricks G., Hlivak P., Kanagaratnam P., Katus H., Kautzner J., Kriebel T., Lancellotti P., Landmesser U., Leclercq C., Lewis B., Lopatin Y., Merkely B., Paul T., Pavlovic N., Petersen S., Petronio A. S., Potpara T., Roffi M., Scherr D., Shlyakhto E., Simpson I. A., Zeppenfeld K., Windecker S., Baigent C., Collet J. -P., Dean V., Gale C. P., Grobbee D. E., Halvorsen S., Iung B., Juni P., Lettino M., Mueller C., Richter D. J., Sousa-Uva M., Touyz R. M., Amara W., Grigoryan S., Podczeck-Schweighofer A., Chasnoits A., Vandekerckhove Y., Sokolovich S., Traykov V., Skoric B., Papasavvas E., Riahi S., Kampus P., Parikka H., Piot O., Etsadashvili K., Stellbrink C., Manolis A. S., Csanadi Z., Gudmundsson K., Erwin J., Barsheshet A., De Ponti R., Abdrakhmanov A., Jashari H., Lunegova O., Jubele K., Refaat M. M., Puodziukynas A., Groben L., Grosu A., Ibtissam F., Trines S. A., Poposka L., Haugaa K. H., Kowalski O., Cavaco D., Dobreanu D., Mikhaylov E. N., Zavatta M., Nebojsa M., Ferreira-Gonzalez I., Juhlin T., Reichlin T., Haouala H., Akgun T., Gupta D., Brugada, J, Katritsis, D, Arbelo, E, Arribas, F, Bax, J, Blomstrom-Lundqvist, C, Calkins, H, Corrado, D, Deftereos, S, Diller, G, Gomez-Doblas, J, Gorenek, B, Grace, A, Ho, S, Kaski, J, Kuck, K, Lambiase, P, Sacher, F, Sarquella-Brugada, G, Suwalski, P, Zaza, A, De Potter, T, Sticherling, C, Aboyans, V, Basso, C, Bocchiardo, M, Budts, W, Delgado, V, Dobrev, D, Fitzsimons, D, Gevaert, S, Heidbuchel, H, Hindricks, G, Hlivak, P, Kanagaratnam, P, Katus, H, Kautzner, J, Kriebel, T, Lancellotti, P, Landmesser, U, Leclercq, C, Lewis, B, Lopatin, Y, Merkely, B, Paul, T, Pavlovic, N, Petersen, S, Petronio, A, Potpara, T, Roffi, M, Scherr, D, Shlyakhto, E, Simpson, I, Zeppenfeld, K, Windecker, S, Baigent, C, Collet, J, Dean, V, Gale, C, Grobbee, D, Halvorsen, S, Iung, B, Juni, P, Lettino, M, Mueller, C, Richter, D, Sousa-Uva, M, Touyz, R, Amara, W, Grigoryan, S, Podczeck-Schweighofer, A, Chasnoits, A, Vandekerckhove, Y, Sokolovich, S, Traykov, V, Skoric, B, Papasavvas, E, Riahi, S, Kampus, P, Parikka, H, Piot, O, Etsadashvili, K, Stellbrink, C, Manolis, A, Csanadi, Z, Gudmundsson, K, Erwin, J, Barsheshet, A, De Ponti, R, Abdrakhmanov, A, Jashari, H, Lunegova, O, Jubele, K, Refaat, M, Puodziukynas, A, Groben, L, Grosu, A, Ibtissam, F, Trines, S, Poposka, L, Haugaa, K, Kowalski, O, Cavaco, D, Dobreanu, D, Mikhaylov, E, Zavatta, M, Nebojsa, M, Ferreira-Gonzalez, I, Juhlin, T, Reichlin, T, Haouala, H, Akgun, T, Gupta, D, Brugada J., Katritsis D. G., Arbelo E., Arribas F., Bax J. J., Blomstrom-Lundqvist C., Calkins H., Corrado D., Deftereos S. G., Diller G. -P., Gomez-Doblas J. J., Gorenek B., Grace A., Ho S. Y., Kaski J. -C., Kuck K. -H., Lambiase P. D., Sacher F., Sarquella-Brugada G., Suwalski P., Zaza A., De Potter T., Sticherling C., Aboyans V., Basso C., Bocchiardo M., Budts W., Delgado V., Dobrev D., Fitzsimons D., Gevaert S., Heidbuchel H., Hindricks G., Hlivak P., Kanagaratnam P., Katus H., Kautzner J., Kriebel T., Lancellotti P., Landmesser U., Leclercq C., Lewis B., Lopatin Y., Merkely B., Paul T., Pavlovic N., Petersen S., Petronio A. S., Potpara T., Roffi M., Scherr D., Shlyakhto E., Simpson I. A., Zeppenfeld K., Windecker S., Baigent C., Collet J. -P., Dean V., Gale C. P., Grobbee D. E., Halvorsen S., Iung B., Juni P., Lettino M., Mueller C., Richter D. J., Sousa-Uva M., Touyz R. M., Amara W., Grigoryan S., Podczeck-Schweighofer A., Chasnoits A., Vandekerckhove Y., Sokolovich S., Traykov V., Skoric B., Papasavvas E., Riahi S., Kampus P., Parikka H., Piot O., Etsadashvili K., Stellbrink C., Manolis A. S., Csanadi Z., Gudmundsson K., Erwin J., Barsheshet A., De Ponti R., Abdrakhmanov A., Jashari H., Lunegova O., Jubele K., Refaat M. M., Puodziukynas A., Groben L., Grosu A., Ibtissam F., Trines S. A., Poposka L., Haugaa K. H., Kowalski O., Cavaco D., Dobreanu D., Mikhaylov E. N., Zavatta M., Nebojsa M., Ferreira-Gonzalez I., Juhlin T., Reichlin T., Haouala H., Akgun T., and Gupta D.

Abstract

E' una "linea-guida" non esiste abstract.

Published
2020

4. 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

5. 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

6. International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)

Author

Beyer-Westendorf, J, Camm, A, Fox, K, Le Heuzey, J, Haas, S, Turpie, A, Virdone, S, Kakkar, A, Pieper, K, Kayani, G, Gersh, B, Hildebrandt, P, Dominguez, H, Comuth, W, Frost, L, Moller, D, Christensen, H, Bruun, L, Milhem, A, Gauthier, J, Mielot, C, Chanseaume, S, Chopra, S, Amlaiky, A, Tricot, O, Sierra, V, Dompnier, A, Zannad, N, Pinzani, A, Quatre, A, Mansourati, J, Fauchier, L, Badenco, N, Gandjbakhch, E, Chachoua, K, Malquarti, V, Pierron, F, Sacher, F, Taieb, J, Davy, J, Marijon, E, Lellouche, N, Leenhardt, A, Salem, A, Lesto, I, Muller, J, Garcia, R, Neau, J, Berneau, J, Schon, N, Gulba, D, Appel, K, Merke, J, Dshabrailov, J, Bauknecht, C, Scheuermann, O, Schroder, T, Jung, W, Kopf, A, Brachmann, J, Leschke, M, Taggeselle, J, Seige, M, Lassig, T, Appel, S, Schmiedl, M, Muller, K, Heinz, G, Axthelm, C, Eberhard, K, Hugl, B, Schwarz, T, Sechtem, U, Falanga, A, Rubino, V, Calo, L, Ageno, W, Massari, F, Imberti, D, Di Gennaro, L, Gaita, F, Margonato, A, Cannava, G, Capasso, F, Diemberger, I, Pelliccia, F, Cafolla, A, Bardari, S, Mattei, L, Ruocco, L, Boriani, G, Poli, D, Testa, S, Indolfi, C, Quintavalla, R, Mos, L, Ladyjanskaia, G, Aksoy, I, Van De Wetering, M, Theunissen, L, Den Hartog, F, Nijmeijer, R, Van De Wal, R, Reinders, S, Patterson, M, Melker, E, Troquay, R, Korecki, J, Szyszka, A, Diks, F, Sumis, J, Cygler, J, Miklaszewicz, B, Litwiejko-Pietrynczak, E, Napora, P, Drelich, G, Kawka-Urbanek, T, Wranicz, J, Mierzejewski, M, Drzewiecka, A, Wronska, D, Fares, I, Baska, J, Stania, K, Krzyzanowski, W, Miekus, P, Tyminski, M, Dronov, D, Zenin, S, Isaeva, E, Lopukhov, A, Yakusevich, V, Kuznetsov, D, Kameneva, T, Pokushalov, E, Karetnikova, V, Dik, I, Karpushina, I, Nikolin, D, Doletsky, A, Ardashev, A, Timofeeva, A, Miller, O, Lyamina, N, Shubik, Y, Boldueva, S, Blanco Coronado, J, Gonzalez Juanatey, C, Otero, E, Alonso, D, Torres Llergo, J, Gonzalez Lama, J, De Prada Tiffe, J, Garcia Seara, F, Gomez Doblas, J, Riancho, J, Clua-Espuny, J, Motero, J, Arrarte, V, Martin Raymondi, D, Isasti Aizpurua, G, Marin, F, Nieto, J, Fernandez Portales, J, Alvarez Garcia, P, Torstensson, I, Cederin, B, Kalm, T, Rosenqvist, U, Thulin, J, Hajimirsadeghi, A, Crisby, M, Manoj, A, Bakhai, A, Mistri, A, Krishnan, M, Kumar, S, Kirubakaran, S, Thomas, H, Camm, J, Ahmed, F, Ross, A, Barry, K, Stockwell, R, Broadley, A, Mamun, M, Chatterjee, K, Cooke, J, Mccready, J, Dutta, D, John, K, Pandya, P, Howlett, R, Vinson, P, Lim, Foley, P, Bruce, D, Dixit, A, Broughton, D, Taylor, J, Schilling, R, Leon, K, Saeed, K, Shaheen, S, Tawfik, M, Mortadda, A, Seleem, M, Aly, M, Kazamel, G, Elbadry, M, Kamal, S, Hassan, M, Mostafa, M, Medhat, M, Ekhlas, Ghaleb, R, Taha, M, Daoud, I, Al Din, H, Imam, A, El Hameed, M, Helmy, Al-Murayeh, M, Akhtar, N, Matto, B, Ghani, M, Amoudi, O, Morsy, M, Bashir, A, Al Hossni, Y, Al Ghamdi, B, Zia-Ul-Sabah, Mir, S, Dardir, D, Masswary, A, Al Shehri, A, Iqbal, J, Almansori, M, Venkitachalam, C, Kurian, J, Rao, J, Aisheh, A, Albawab, A, Subbaraman, B, Amanat, A, Esfehani, K, Lochan, R, Bin Brek, A, Mittal, B, Ghazi, Y, Krishna, M, Tabatabaei, S, Thoppil, P, Nasim, S, El Khider Nour, S, Barros, P, Almeida, A, Andrade, M, Garbelini, B, Silvestrini, T, Alves, A, De Lima, C, Kormann, A, De Lima, G, Halperin, C, Salvadori Junior, D, Freitas, A, Gemelli, J, Ornelas, C, Dantas, J, Aziz, J, Backes, L, Barroso, W, Paiva, M, De Figueiredo Neto, J, Dos Santos, F, De Lima Neto, J, Bergo, R, Salvador Junior, P, Lopez, A, Alva, J, Gamba, M, Padilla-Padilla, F, Ruiz, A, Berlingieri, J, Bakbak, A, Gupta, M, Saunders, K, Costa-Vitali, A, Beaudry, P, Bhargava, R, Khaykin, Y, Healey, J, Crystal, E, Nadeau, D, Begg, A, Anderson, C, Baveja, S, Cross, D, Catanchin, A, Brieger, D, Lim, K, Davidson, P, Tan, R, Bhindi, R, Hickey, J, Layland, J, Bloch, M, Itty, C, Singh, B, Carroll, P, Lee, A, Starmer, G, Lehman, R, Beyer-Westendorf J., Camm A. J., Fox K. A. A., Le Heuzey J. -Y., Haas S., Turpie A. G. G., Virdone S., Kakkar A. K., Pieper K. S., Kayani G., Gersh B. J., Hildebrandt P., Dominguez H., Comuth W., Frost L., Moller D. S., Christensen H., Bruun L. M., Milhem A., Gauthier J., Mielot C., Chanseaume S., Chopra S., Amlaiky A., Tricot O., Sierra V., Dompnier A., Zannad N., Pinzani A., Quatre A., Mansourati J., Fauchier L., Badenco N., Gandjbakhch E., Chachoua K. F., Malquarti V., Pierron F., Sacher F., Taieb J., Davy J. M., Marijon E., Lellouche N., Leenhardt A., Salem A., Lesto I., Muller J. J., Garcia R., Neau J. P., Berneau J. B., Schon N., Gulba D., Appel K. F., Merke J., Dshabrailov J., Bauknecht C., Scheuermann O., Schroder T., Jung W., Kopf A., Brachmann J., Leschke M., Taggeselle J., Seige M., Lassig T., Appel S., Schmiedl M., Muller K., Heinz G. U., Axthelm C., Eberhard K., Hugl B., Schwarz T., Sechtem U., Falanga A., Rubino V., Calo L., Ageno W., Massari F., Imberti D., Di Gennaro L., Gaita F., Margonato A., Cannava G., Capasso F., Diemberger I., Pelliccia F., Cafolla A., Bardari S., Mattei L., Ruocco L., Boriani G., Poli D., Testa S., Indolfi C., Quintavalla R., Mos L., Ladyjanskaia G., Aksoy I., Van De Wetering M., Theunissen L., Den Hartog F., Nijmeijer R., Van De Wal R., Reinders S., Patterson M., Melker E. D., Troquay R., Korecki J., Szyszka A., Diks F., Sumis J., Cygler J., Miklaszewicz B., Litwiejko-Pietrynczak E., Napora P., Drelich G., Kawka-Urbanek T., Wranicz J. K., Mierzejewski M., Drzewiecka A., Wronska D., Fares I., Baska J., Stania K., Krzyzanowski W., Miekus P., Tyminski M., Dronov D., Zenin S., Isaeva E., Lopukhov A., Yakusevich V., Kuznetsov D., Kameneva T., Pokushalov E., Karetnikova V., Dik I., Karpushina I., Nikolin D., Doletsky A., Ardashev A., Timofeeva A., Miller O., Lyamina N., Shubik Y., Boldueva S., Blanco Coronado J. L., Gonzalez Juanatey C., Otero E., Alonso D., Torres Llergo J., Gonzalez Lama J., De Prada Tiffe J. A. V., Garcia Seara F. J., Gomez Doblas J. J., Riancho J. A., Clua-Espuny J. L., Motero J., Arrarte V. I., Martin Raymondi D., Isasti Aizpurua G., Marin F., Nieto J. A., Fernandez Portales J., Alvarez Garcia P., Torstensson I., Cederin B., Kalm T., Rosenqvist U., Thulin J., Hajimirsadeghi A., Crisby M., Manoj A., Bakhai A., Mistri A., Krishnan M., Kumar S., Kirubakaran S., Thomas H., Camm J., Ahmed F., Ross A. M., Barry K., Stockwell R., Broadley A., Mamun M., Chatterjee K., Cooke J., McCready J., Dutta D., John K., Pandya P., Howlett R., Vinson P., Foley P., Bruce D., Dixit A., Broughton D., Taylor J., Schilling R., Leon K., Saeed K., Shaheen S., Tawfik M., Mortadda A., Seleem M., Aly M. S. I., Kazamel G., Elbadry M., Kamal S., Hassan M., Mostafa M., Medhat M. E. S., Ghaleb R., Taha M. O., Daoud I., Al Din H., Imam A. M., El Hameed M. A., Al-Murayeh M., Akhtar N., Matto B. M., Ghani M. A., Amoudi O. A., Morsy M. M., Bashir A. A. F., Al Hossni Y. M., Al Ghamdi B., Mir S., Dardir D., Masswary A., Al Shehri A. R., Iqbal J., Almansori M. A. J., Venkitachalam C. G., Kurian J., Rao J., Aisheh A., Albawab A. A., Subbaraman B., Amanat A., Esfehani K. J., Lochan R., Bin Brek A., Mittal B., Ghazi Y., Krishna M., Tabatabaei S. B., Thoppil P. S., Nasim S., El Khider Nour S., Barros P., Almeida A. P., Andrade M., Garbelini B., Silvestrini T. L., Alves A. R., De Lima C. E. B., Kormann A., De Lima G. G., Halperin C., Salvadori Junior D., Freitas A. F., Gemelli J. R., Ornelas C. E., Dantas J. M. M., Aziz J. L., Backes L. M., Barroso W. S., Paiva M. S., De Figueiredo Neto J. A., Dos Santos F. R., De Lima Neto J. A., Bergo R., Salvador Junior P. R., Lopez A. G., Alva J. C. P., Gamba M. A. A., Padilla-Padilla F. G., Ruiz A. E. B., Berlingieri J., Bakbak A., Gupta M., Saunders K., Costa-Vitali A., Beaudry P. R., Bhargava R., Khaykin Y., Healey J. S., Crystal E., Nadeau Dhillon, Begg A., Anderson C., Baveja S., Cross D., Catanchin A., Brieger D., Lim K. T., Davidson P., Tan R., Bhindi R., Hickey J., Layland J., Bloch M., Itty C., Singh B., Carroll P., Lee A., Starmer G., Lehman R., Beyer-Westendorf, J, Camm, A, Fox, K, Le Heuzey, J, Haas, S, Turpie, A, Virdone, S, Kakkar, A, Pieper, K, Kayani, G, Gersh, B, Hildebrandt, P, Dominguez, H, Comuth, W, Frost, L, Moller, D, Christensen, H, Bruun, L, Milhem, A, Gauthier, J, Mielot, C, Chanseaume, S, Chopra, S, Amlaiky, A, Tricot, O, Sierra, V, Dompnier, A, Zannad, N, Pinzani, A, Quatre, A, Mansourati, J, Fauchier, L, Badenco, N, Gandjbakhch, E, Chachoua, K, Malquarti, V, Pierron, F, Sacher, F, Taieb, J, Davy, J, Marijon, E, Lellouche, N, Leenhardt, A, Salem, A, Lesto, I, Muller, J, Garcia, R, Neau, J, Berneau, J, Schon, N, Gulba, D, Appel, K, Merke, J, Dshabrailov, J, Bauknecht, C, Scheuermann, O, Schroder, T, Jung, W, Kopf, A, Brachmann, J, Leschke, M, Taggeselle, J, Seige, M, Lassig, T, Appel, S, Schmiedl, M, Muller, K, Heinz, G, Axthelm, C, Eberhard, K, Hugl, B, Schwarz, T, Sechtem, U, Falanga, A, Rubino, V, Calo, L, Ageno, W, Massari, F, Imberti, D, Di Gennaro, L, Gaita, F, Margonato, A, Cannava, G, Capasso, F, Diemberger, I, Pelliccia, F, Cafolla, A, Bardari, S, Mattei, L, Ruocco, L, Boriani, G, Poli, D, Testa, S, Indolfi, C, Quintavalla, R, Mos, L, Ladyjanskaia, G, Aksoy, I, Van De Wetering, M, Theunissen, L, Den Hartog, F, Nijmeijer, R, Van De Wal, R, Reinders, S, Patterson, M, Melker, E, Troquay, R, Korecki, J, Szyszka, A, Diks, F, Sumis, J, Cygler, J, Miklaszewicz, B, Litwiejko-Pietrynczak, E, Napora, P, Drelich, G, Kawka-Urbanek, T, Wranicz, J, Mierzejewski, M, Drzewiecka, A, Wronska, D, Fares, I, Baska, J, Stania, K, Krzyzanowski, W, Miekus, P, Tyminski, M, Dronov, D, Zenin, S, Isaeva, E, Lopukhov, A, Yakusevich, V, Kuznetsov, D, Kameneva, T, Pokushalov, E, Karetnikova, V, Dik, I, Karpushina, I, Nikolin, D, Doletsky, A, Ardashev, A, Timofeeva, A, Miller, O, Lyamina, N, Shubik, Y, Boldueva, S, Blanco Coronado, J, Gonzalez Juanatey, C, Otero, E, Alonso, D, Torres Llergo, J, Gonzalez Lama, J, De Prada Tiffe, J, Garcia Seara, F, Gomez Doblas, J, Riancho, J, Clua-Espuny, J, Motero, J, Arrarte, V, Martin Raymondi, D, Isasti Aizpurua, G, Marin, F, Nieto, J, Fernandez Portales, J, Alvarez Garcia, P, Torstensson, I, Cederin, B, Kalm, T, Rosenqvist, U, Thulin, J, Hajimirsadeghi, A, Crisby, M, Manoj, A, Bakhai, A, Mistri, A, Krishnan, M, Kumar, S, Kirubakaran, S, Thomas, H, Camm, J, Ahmed, F, Ross, A, Barry, K, Stockwell, R, Broadley, A, Mamun, M, Chatterjee, K, Cooke, J, Mccready, J, Dutta, D, John, K, Pandya, P, Howlett, R, Vinson, P, Lim, Foley, P, Bruce, D, Dixit, A, Broughton, D, Taylor, J, Schilling, R, Leon, K, Saeed, K, Shaheen, S, Tawfik, M, Mortadda, A, Seleem, M, Aly, M, Kazamel, G, Elbadry, M, Kamal, S, Hassan, M, Mostafa, M, Medhat, M, Ekhlas, Ghaleb, R, Taha, M, Daoud, I, Al Din, H, Imam, A, El Hameed, M, Helmy, Al-Murayeh, M, Akhtar, N, Matto, B, Ghani, M, Amoudi, O, Morsy, M, Bashir, A, Al Hossni, Y, Al Ghamdi, B, Zia-Ul-Sabah, Mir, S, Dardir, D, Masswary, A, Al Shehri, A, Iqbal, J, Almansori, M, Venkitachalam, C, Kurian, J, Rao, J, Aisheh, A, Albawab, A, Subbaraman, B, Amanat, A, Esfehani, K, Lochan, R, Bin Brek, A, Mittal, B, Ghazi, Y, Krishna, M, Tabatabaei, S, Thoppil, P, Nasim, S, El Khider Nour, S, Barros, P, Almeida, A, Andrade, M, Garbelini, B, Silvestrini, T, Alves, A, De Lima, C, Kormann, A, De Lima, G, Halperin, C, Salvadori Junior, D, Freitas, A, Gemelli, J, Ornelas, C, Dantas, J, Aziz, J, Backes, L, Barroso, W, Paiva, M, De Figueiredo Neto, J, Dos Santos, F, De Lima Neto, J, Bergo, R, Salvador Junior, P, Lopez, A, Alva, J, Gamba, M, Padilla-Padilla, F, Ruiz, A, Berlingieri, J, Bakbak, A, Gupta, M, Saunders, K, Costa-Vitali, A, Beaudry, P, Bhargava, R, Khaykin, Y, Healey, J, Crystal, E, Nadeau, D, Begg, A, Anderson, C, Baveja, S, Cross, D, Catanchin, A, Brieger, D, Lim, K, Davidson, P, Tan, R, Bhindi, R, Hickey, J, Layland, J, Bloch, M, Itty, C, Singh, B, Carroll, P, Lee, A, Starmer, G, Lehman, R, Beyer-Westendorf J., Camm A. J., Fox K. A. A., Le Heuzey J. -Y., Haas S., Turpie A. G. G., Virdone S., Kakkar A. K., Pieper K. S., Kayani G., Gersh B. J., Hildebrandt P., Dominguez H., Comuth W., Frost L., Moller D. S., Christensen H., Bruun L. M., Milhem A., Gauthier J., Mielot C., Chanseaume S., Chopra S., Amlaiky A., Tricot O., Sierra V., Dompnier A., Zannad N., Pinzani A., Quatre A., Mansourati J., Fauchier L., Badenco N., Gandjbakhch E., Chachoua K. F., Malquarti V., Pierron F., Sacher F., Taieb J., Davy J. M., Marijon E., Lellouche N., Leenhardt A., Salem A., Lesto I., Muller J. J., Garcia R., Neau J. P., Berneau J. B., Schon N., Gulba D., Appel K. F., Merke J., Dshabrailov J., Bauknecht C., Scheuermann O., Schroder T., Jung W., Kopf A., Brachmann J., Leschke M., Taggeselle J., Seige M., Lassig T., Appel S., Schmiedl M., Muller K., Heinz G. U., Axthelm C., Eberhard K., Hugl B., Schwarz T., Sechtem U., Falanga A., Rubino V., Calo L., Ageno W., Massari F., Imberti D., Di Gennaro L., Gaita F., Margonato A., Cannava G., Capasso F., Diemberger I., Pelliccia F., Cafolla A., Bardari S., Mattei L., Ruocco L., Boriani G., Poli D., Testa S., Indolfi C., Quintavalla R., Mos L., Ladyjanskaia G., Aksoy I., Van De Wetering M., Theunissen L., Den Hartog F., Nijmeijer R., Van De Wal R., Reinders S., Patterson M., Melker E. D., Troquay R., Korecki J., Szyszka A., Diks F., Sumis J., Cygler J., Miklaszewicz B., Litwiejko-Pietrynczak E., Napora P., Drelich G., Kawka-Urbanek T., Wranicz J. K., Mierzejewski M., Drzewiecka A., Wronska D., Fares I., Baska J., Stania K., Krzyzanowski W., Miekus P., Tyminski M., Dronov D., Zenin S., Isaeva E., Lopukhov A., Yakusevich V., Kuznetsov D., Kameneva T., Pokushalov E., Karetnikova V., Dik I., Karpushina I., Nikolin D., Doletsky A., Ardashev A., Timofeeva A., Miller O., Lyamina N., Shubik Y., Boldueva S., Blanco Coronado J. L., Gonzalez Juanatey C., Otero E., Alonso D., Torres Llergo J., Gonzalez Lama J., De Prada Tiffe J. A. V., Garcia Seara F. J., Gomez Doblas J. J., Riancho J. A., Clua-Espuny J. L., Motero J., Arrarte V. I., Martin Raymondi D., Isasti Aizpurua G., Marin F., Nieto J. A., Fernandez Portales J., Alvarez Garcia P., Torstensson I., Cederin B., Kalm T., Rosenqvist U., Thulin J., Hajimirsadeghi A., Crisby M., Manoj A., Bakhai A., Mistri A., Krishnan M., Kumar S., Kirubakaran S., Thomas H., Camm J., Ahmed F., Ross A. M., Barry K., Stockwell R., Broadley A., Mamun M., Chatterjee K., Cooke J., McCready J., Dutta D., John K., Pandya P., Howlett R., Vinson P., Foley P., Bruce D., Dixit A., Broughton D., Taylor J., Schilling R., Leon K., Saeed K., Shaheen S., Tawfik M., Mortadda A., Seleem M., Aly M. S. I., Kazamel G., Elbadry M., Kamal S., Hassan M., Mostafa M., Medhat M. E. S., Ghaleb R., Taha M. O., Daoud I., Al Din H., Imam A. M., El Hameed M. A., Al-Murayeh M., Akhtar N., Matto B. M., Ghani M. A., Amoudi O. A., Morsy M. M., Bashir A. A. F., Al Hossni Y. M., Al Ghamdi B., Mir S., Dardir D., Masswary A., Al Shehri A. R., Iqbal J., Almansori M. A. J., Venkitachalam C. G., Kurian J., Rao J., Aisheh A., Albawab A. A., Subbaraman B., Amanat A., Esfehani K. J., Lochan R., Bin Brek A., Mittal B., Ghazi Y., Krishna M., Tabatabaei S. B., Thoppil P. S., Nasim S., El Khider Nour S., Barros P., Almeida A. P., Andrade M., Garbelini B., Silvestrini T. L., Alves A. R., De Lima C. E. B., Kormann A., De Lima G. G., Halperin C., Salvadori Junior D., Freitas A. F., Gemelli J. R., Ornelas C. E., Dantas J. M. M., Aziz J. L., Backes L. M., Barroso W. S., Paiva M. S., De Figueiredo Neto J. A., Dos Santos F. R., De Lima Neto J. A., Bergo R., Salvador Junior P. R., Lopez A. G., Alva J. C. P., Gamba M. A. A., Padilla-Padilla F. G., Ruiz A. E. B., Berlingieri J., Bakbak A., Gupta M., Saunders K., Costa-Vitali A., Beaudry P. R., Bhargava R., Khaykin Y., Healey J. S., Crystal E., Nadeau Dhillon, Begg A., Anderson C., Baveja S., Cross D., Catanchin A., Brieger D., Lim K. T., Davidson P., Tan R., Bhindi R., Hickey J., Layland J., Bloch M., Itty C., Singh B., Carroll P., Lee A., Starmer G., and Lehman R.

Abstract

Background: Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. Methods and results: Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet the

Published
2019

7. International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)

Author

Beyer-Westendorf, J, Camm, A, Fox, K, Le Heuzey, J, Haas, S, Turpie, A, Virdone, S, Kakkar, A, Pieper, K, Kayani, G, Gersh, B, Hildebrandt, P, Dominguez, H, Comuth, W, Frost, L, Moller, D, Christensen, H, Bruun, L, Milhem, A, Gauthier, J, Mielot, C, Chanseaume, S, Chopra, S, Amlaiky, A, Tricot, O, Sierra, V, Dompnier, A, Zannad, N, Pinzani, A, Quatre, A, Mansourati, J, Fauchier, L, Badenco, N, Gandjbakhch, E, Chachoua, K, Malquarti, V, Pierron, F, Sacher, F, Taieb, J, Davy, J, Marijon, E, Lellouche, N, Leenhardt, A, Salem, A, Lesto, I, Muller, J, Garcia, R, Neau, J, Berneau, J, Schon, N, Gulba, D, Appel, K, Merke, J, Dshabrailov, J, Bauknecht, C, Scheuermann, O, Schroder, T, Jung, W, Kopf, A, Brachmann, J, Leschke, M, Taggeselle, J, Seige, M, Lassig, T, Appel, S, Schmiedl, M, Muller, K, Heinz, G, Axthelm, C, Eberhard, K, Hugl, B, Schwarz, T, Sechtem, U, Falanga, A, Rubino, V, Calo, L, Ageno, W, Massari, F, Imberti, D, Di Gennaro, L, Gaita, F, Margonato, A, Cannava, G, Capasso, F, Diemberger, I, Pelliccia, F, Cafolla, A, Bardari, S, Mattei, L, Ruocco, L, Boriani, G, Poli, D, Testa, S, Indolfi, C, Quintavalla, R, Mos, L, Ladyjanskaia, G, Aksoy, I, Van De Wetering, M, Theunissen, L, Den Hartog, F, Nijmeijer, R, Van De Wal, R, Reinders, S, Patterson, M, Melker, E, Troquay, R, Korecki, J, Szyszka, A, Diks, F, Sumis, J, Cygler, J, Miklaszewicz, B, Litwiejko-Pietrynczak, E, Napora, P, Drelich, G, Kawka-Urbanek, T, Wranicz, J, Mierzejewski, M, Drzewiecka, A, Wronska, D, Fares, I, Baska, J, Stania, K, Krzyzanowski, W, Miekus, P, Tyminski, M, Dronov, D, Zenin, S, Isaeva, E, Lopukhov, A, Yakusevich, V, Kuznetsov, D, Kameneva, T, Pokushalov, E, Karetnikova, V, Dik, I, Karpushina, I, Nikolin, D, Doletsky, A, Ardashev, A, Timofeeva, A, Miller, O, Lyamina, N, Shubik, Y, Boldueva, S, Blanco Coronado, J, Gonzalez Juanatey, C, Otero, E, Alonso, D, Torres Llergo, J, Gonzalez Lama, J, De Prada Tiffe, J, Garcia Seara, F, Gomez Doblas, J, Riancho, J, Clua-Espuny, J, Motero, J, Arrarte, V, Martin Raymondi, D, Isasti Aizpurua, G, Marin, F, Nieto, J, Fernandez Portales, J, Alvarez Garcia, P, Torstensson, I, Cederin, B, Kalm, T, Rosenqvist, U, Thulin, J, Hajimirsadeghi, A, Crisby, M, Manoj, A, Bakhai, A, Mistri, A, Krishnan, M, Kumar, S, Kirubakaran, S, Thomas, H, Camm, J, Ahmed, F, Ross, A, Barry, K, Stockwell, R, Broadley, A, Mamun, M, Chatterjee, K, Cooke, J, Mccready, J, Dutta, D, John, K, Pandya, P, Howlett, R, Vinson, P, Lim, Foley, P, Bruce, D, Dixit, A, Broughton, D, Taylor, J, Schilling, R, Leon, K, Saeed, K, Shaheen, S, Tawfik, M, Mortadda, A, Seleem, M, Aly, M, Kazamel, G, Elbadry, M, Kamal, S, Hassan, M, Mostafa, M, Medhat, M, Ekhlas, Ghaleb, R, Taha, M, Daoud, I, Al Din, H, Imam, A, El Hameed, M, Helmy, Al-Murayeh, M, Akhtar, N, Matto, B, Ghani, M, Amoudi, O, Morsy, M, Bashir, A, Al Hossni, Y, Al Ghamdi, B, Zia-Ul-Sabah, Mir, S, Dardir, D, Masswary, A, Al Shehri, A, Iqbal, J, Almansori, M, Venkitachalam, C, Kurian, J, Rao, J, Aisheh, A, Albawab, A, Subbaraman, B, Amanat, A, Esfehani, K, Lochan, R, Bin Brek, A, Mittal, B, Ghazi, Y, Krishna, M, Tabatabaei, S, Thoppil, P, Nasim, S, El Khider Nour, S, Barros, P, Almeida, A, Andrade, M, Garbelini, B, Silvestrini, T, Alves, A, De Lima, C, Kormann, A, De Lima, G, Halperin, C, Salvadori Junior, D, Freitas, A, Gemelli, J, Ornelas, C, Dantas, J, Aziz, J, Backes, L, Barroso, W, Paiva, M, De Figueiredo Neto, J, Dos Santos, F, De Lima Neto, J, Bergo, R, Salvador Junior, P, Lopez, A, Alva, J, Gamba, M, Padilla-Padilla, F, Ruiz, A, Berlingieri, J, Bakbak, A, Gupta, M, Saunders, K, Costa-Vitali, A, Beaudry, P, Bhargava, R, Khaykin, Y, Healey, J, Crystal, E, Nadeau, D, Begg, A, Anderson, C, Baveja, S, Cross, D, Catanchin, A, Brieger, D, Lim, K, Davidson, P, Tan, R, Bhindi, R, Hickey, J, Layland, J, Bloch, M, Itty, C, Singh, B, Carroll, P, Lee, A, Starmer, G, Lehman, R, Beyer-Westendorf J., Camm A. J., Fox K. A. A., Le Heuzey J. -Y., Haas S., Turpie A. G. G., Virdone S., Kakkar A. K., Pieper K. S., Kayani G., Gersh B. J., Hildebrandt P., Dominguez H., Comuth W., Frost L., Moller D. S., Christensen H., Bruun L. M., Milhem A., Gauthier J., Mielot C., Chanseaume S., Chopra S., Amlaiky A., Tricot O., Sierra V., Dompnier A., Zannad N., Pinzani A., Quatre A., Mansourati J., Fauchier L., Badenco N., Gandjbakhch E., Chachoua K. F., Malquarti V., Pierron F., Sacher F., Taieb J., Davy J. M., Marijon E., Lellouche N., Leenhardt A., Salem A., Lesto I., Muller J. J., Garcia R., Neau J. P., Berneau J. B., Schon N., Gulba D., Appel K. F., Merke J., Dshabrailov J., Bauknecht C., Scheuermann O., Schroder T., Jung W., Kopf A., Brachmann J., Leschke M., Taggeselle J., Seige M., Lassig T., Appel S., Schmiedl M., Muller K., Heinz G. U., Axthelm C., Eberhard K., Hugl B., Schwarz T., Sechtem U., Falanga A., Rubino V., Calo L., Ageno W., Massari F., Imberti D., Di Gennaro L., Gaita F., Margonato A., Cannava G., Capasso F., Diemberger I., Pelliccia F., Cafolla A., Bardari S., Mattei L., Ruocco L., Boriani G., Poli D., Testa S., Indolfi C., Quintavalla R., Mos L., Ladyjanskaia G., Aksoy I., Van De Wetering M., Theunissen L., Den Hartog F., Nijmeijer R., Van De Wal R., Reinders S., Patterson M., Melker E. D., Troquay R., Korecki J., Szyszka A., Diks F., Sumis J., Cygler J., Miklaszewicz B., Litwiejko-Pietrynczak E., Napora P., Drelich G., Kawka-Urbanek T., Wranicz J. K., Mierzejewski M., Drzewiecka A., Wronska D., Fares I., Baska J., Stania K., Krzyzanowski W., Miekus P., Tyminski M., Dronov D., Zenin S., Isaeva E., Lopukhov A., Yakusevich V., Kuznetsov D., Kameneva T., Pokushalov E., Karetnikova V., Dik I., Karpushina I., Nikolin D., Doletsky A., Ardashev A., Timofeeva A., Miller O., Lyamina N., Shubik Y., Boldueva S., Blanco Coronado J. L., Gonzalez Juanatey C., Otero E., Alonso D., Torres Llergo J., Gonzalez Lama J., De Prada Tiffe J. A. V., Garcia Seara F. J., Gomez Doblas J. J., Riancho J. A., Clua-Espuny J. L., Motero J., Arrarte V. I., Martin Raymondi D., Isasti Aizpurua G., Marin F., Nieto J. A., Fernandez Portales J., Alvarez Garcia P., Torstensson I., Cederin B., Kalm T., Rosenqvist U., Thulin J., Hajimirsadeghi A., Crisby M., Manoj A., Bakhai A., Mistri A., Krishnan M., Kumar S., Kirubakaran S., Thomas H., Camm J., Ahmed F., Ross A. M., Barry K., Stockwell R., Broadley A., Mamun M., Chatterjee K., Cooke J., McCready J., Dutta D., John K., Pandya P., Howlett R., Vinson P., Foley P., Bruce D., Dixit A., Broughton D., Taylor J., Schilling R., Leon K., Saeed K., Shaheen S., Tawfik M., Mortadda A., Seleem M., Aly M. S. I., Kazamel G., Elbadry M., Kamal S., Hassan M., Mostafa M., Medhat M. E. S., Ghaleb R., Taha M. O., Daoud I., Al Din H., Imam A. M., El Hameed M. A., Al-Murayeh M., Akhtar N., Matto B. M., Ghani M. A., Amoudi O. A., Morsy M. M., Bashir A. A. F., Al Hossni Y. M., Al Ghamdi B., Mir S., Dardir D., Masswary A., Al Shehri A. R., Iqbal J., Almansori M. A. J., Venkitachalam C. G., Kurian J., Rao J., Aisheh A., Albawab A. A., Subbaraman B., Amanat A., Esfehani K. J., Lochan R., Bin Brek A., Mittal B., Ghazi Y., Krishna M., Tabatabaei S. B., Thoppil P. S., Nasim S., El Khider Nour S., Barros P., Almeida A. P., Andrade M., Garbelini B., Silvestrini T. L., Alves A. R., De Lima C. E. B., Kormann A., De Lima G. G., Halperin C., Salvadori Junior D., Freitas A. F., Gemelli J. R., Ornelas C. E., Dantas J. M. M., Aziz J. L., Backes L. M., Barroso W. S., Paiva M. S., De Figueiredo Neto J. A., Dos Santos F. R., De Lima Neto J. A., Bergo R., Salvador Junior P. R., Lopez A. G., Alva J. C. P., Gamba M. A. A., Padilla-Padilla F. G., Ruiz A. E. B., Berlingieri J., Bakbak A., Gupta M., Saunders K., Costa-Vitali A., Beaudry P. R., Bhargava R., Khaykin Y., Healey J. S., Crystal E., Nadeau Dhillon, Begg A., Anderson C., Baveja S., Cross D., Catanchin A., Brieger D., Lim K. T., Davidson P., Tan R., Bhindi R., Hickey J., Layland J., Bloch M., Itty C., Singh B., Carroll P., Lee A., Starmer G., Lehman R., Beyer-Westendorf, J, Camm, A, Fox, K, Le Heuzey, J, Haas, S, Turpie, A, Virdone, S, Kakkar, A, Pieper, K, Kayani, G, Gersh, B, Hildebrandt, P, Dominguez, H, Comuth, W, Frost, L, Moller, D, Christensen, H, Bruun, L, Milhem, A, Gauthier, J, Mielot, C, Chanseaume, S, Chopra, S, Amlaiky, A, Tricot, O, Sierra, V, Dompnier, A, Zannad, N, Pinzani, A, Quatre, A, Mansourati, J, Fauchier, L, Badenco, N, Gandjbakhch, E, Chachoua, K, Malquarti, V, Pierron, F, Sacher, F, Taieb, J, Davy, J, Marijon, E, Lellouche, N, Leenhardt, A, Salem, A, Lesto, I, Muller, J, Garcia, R, Neau, J, Berneau, J, Schon, N, Gulba, D, Appel, K, Merke, J, Dshabrailov, J, Bauknecht, C, Scheuermann, O, Schroder, T, Jung, W, Kopf, A, Brachmann, J, Leschke, M, Taggeselle, J, Seige, M, Lassig, T, Appel, S, Schmiedl, M, Muller, K, Heinz, G, Axthelm, C, Eberhard, K, Hugl, B, Schwarz, T, Sechtem, U, Falanga, A, Rubino, V, Calo, L, Ageno, W, Massari, F, Imberti, D, Di Gennaro, L, Gaita, F, Margonato, A, Cannava, G, Capasso, F, Diemberger, I, Pelliccia, F, Cafolla, A, Bardari, S, Mattei, L, Ruocco, L, Boriani, G, Poli, D, Testa, S, Indolfi, C, Quintavalla, R, Mos, L, Ladyjanskaia, G, Aksoy, I, Van De Wetering, M, Theunissen, L, Den Hartog, F, Nijmeijer, R, Van De Wal, R, Reinders, S, Patterson, M, Melker, E, Troquay, R, Korecki, J, Szyszka, A, Diks, F, Sumis, J, Cygler, J, Miklaszewicz, B, Litwiejko-Pietrynczak, E, Napora, P, Drelich, G, Kawka-Urbanek, T, Wranicz, J, Mierzejewski, M, Drzewiecka, A, Wronska, D, Fares, I, Baska, J, Stania, K, Krzyzanowski, W, Miekus, P, Tyminski, M, Dronov, D, Zenin, S, Isaeva, E, Lopukhov, A, Yakusevich, V, Kuznetsov, D, Kameneva, T, Pokushalov, E, Karetnikova, V, Dik, I, Karpushina, I, Nikolin, D, Doletsky, A, Ardashev, A, Timofeeva, A, Miller, O, Lyamina, N, Shubik, Y, Boldueva, S, Blanco Coronado, J, Gonzalez Juanatey, C, Otero, E, Alonso, D, Torres Llergo, J, Gonzalez Lama, J, De Prada Tiffe, J, Garcia Seara, F, Gomez Doblas, J, Riancho, J, Clua-Espuny, J, Motero, J, Arrarte, V, Martin Raymondi, D, Isasti Aizpurua, G, Marin, F, Nieto, J, Fernandez Portales, J, Alvarez Garcia, P, Torstensson, I, Cederin, B, Kalm, T, Rosenqvist, U, Thulin, J, Hajimirsadeghi, A, Crisby, M, Manoj, A, Bakhai, A, Mistri, A, Krishnan, M, Kumar, S, Kirubakaran, S, Thomas, H, Camm, J, Ahmed, F, Ross, A, Barry, K, Stockwell, R, Broadley, A, Mamun, M, Chatterjee, K, Cooke, J, Mccready, J, Dutta, D, John, K, Pandya, P, Howlett, R, Vinson, P, Lim, Foley, P, Bruce, D, Dixit, A, Broughton, D, Taylor, J, Schilling, R, Leon, K, Saeed, K, Shaheen, S, Tawfik, M, Mortadda, A, Seleem, M, Aly, M, Kazamel, G, Elbadry, M, Kamal, S, Hassan, M, Mostafa, M, Medhat, M, Ekhlas, Ghaleb, R, Taha, M, Daoud, I, Al Din, H, Imam, A, El Hameed, M, Helmy, Al-Murayeh, M, Akhtar, N, Matto, B, Ghani, M, Amoudi, O, Morsy, M, Bashir, A, Al Hossni, Y, Al Ghamdi, B, Zia-Ul-Sabah, Mir, S, Dardir, D, Masswary, A, Al Shehri, A, Iqbal, J, Almansori, M, Venkitachalam, C, Kurian, J, Rao, J, Aisheh, A, Albawab, A, Subbaraman, B, Amanat, A, Esfehani, K, Lochan, R, Bin Brek, A, Mittal, B, Ghazi, Y, Krishna, M, Tabatabaei, S, Thoppil, P, Nasim, S, El Khider Nour, S, Barros, P, Almeida, A, Andrade, M, Garbelini, B, Silvestrini, T, Alves, A, De Lima, C, Kormann, A, De Lima, G, Halperin, C, Salvadori Junior, D, Freitas, A, Gemelli, J, Ornelas, C, Dantas, J, Aziz, J, Backes, L, Barroso, W, Paiva, M, De Figueiredo Neto, J, Dos Santos, F, De Lima Neto, J, Bergo, R, Salvador Junior, P, Lopez, A, Alva, J, Gamba, M, Padilla-Padilla, F, Ruiz, A, Berlingieri, J, Bakbak, A, Gupta, M, Saunders, K, Costa-Vitali, A, Beaudry, P, Bhargava, R, Khaykin, Y, Healey, J, Crystal, E, Nadeau, D, Begg, A, Anderson, C, Baveja, S, Cross, D, Catanchin, A, Brieger, D, Lim, K, Davidson, P, Tan, R, Bhindi, R, Hickey, J, Layland, J, Bloch, M, Itty, C, Singh, B, Carroll, P, Lee, A, Starmer, G, Lehman, R, Beyer-Westendorf J., Camm A. J., Fox K. A. A., Le Heuzey J. -Y., Haas S., Turpie A. G. G., Virdone S., Kakkar A. K., Pieper K. S., Kayani G., Gersh B. J., Hildebrandt P., Dominguez H., Comuth W., Frost L., Moller D. S., Christensen H., Bruun L. M., Milhem A., Gauthier J., Mielot C., Chanseaume S., Chopra S., Amlaiky A., Tricot O., Sierra V., Dompnier A., Zannad N., Pinzani A., Quatre A., Mansourati J., Fauchier L., Badenco N., Gandjbakhch E., Chachoua K. F., Malquarti V., Pierron F., Sacher F., Taieb J., Davy J. M., Marijon E., Lellouche N., Leenhardt A., Salem A., Lesto I., Muller J. J., Garcia R., Neau J. P., Berneau J. B., Schon N., Gulba D., Appel K. F., Merke J., Dshabrailov J., Bauknecht C., Scheuermann O., Schroder T., Jung W., Kopf A., Brachmann J., Leschke M., Taggeselle J., Seige M., Lassig T., Appel S., Schmiedl M., Muller K., Heinz G. U., Axthelm C., Eberhard K., Hugl B., Schwarz T., Sechtem U., Falanga A., Rubino V., Calo L., Ageno W., Massari F., Imberti D., Di Gennaro L., Gaita F., Margonato A., Cannava G., Capasso F., Diemberger I., Pelliccia F., Cafolla A., Bardari S., Mattei L., Ruocco L., Boriani G., Poli D., Testa S., Indolfi C., Quintavalla R., Mos L., Ladyjanskaia G., Aksoy I., Van De Wetering M., Theunissen L., Den Hartog F., Nijmeijer R., Van De Wal R., Reinders S., Patterson M., Melker E. D., Troquay R., Korecki J., Szyszka A., Diks F., Sumis J., Cygler J., Miklaszewicz B., Litwiejko-Pietrynczak E., Napora P., Drelich G., Kawka-Urbanek T., Wranicz J. K., Mierzejewski M., Drzewiecka A., Wronska D., Fares I., Baska J., Stania K., Krzyzanowski W., Miekus P., Tyminski M., Dronov D., Zenin S., Isaeva E., Lopukhov A., Yakusevich V., Kuznetsov D., Kameneva T., Pokushalov E., Karetnikova V., Dik I., Karpushina I., Nikolin D., Doletsky A., Ardashev A., Timofeeva A., Miller O., Lyamina N., Shubik Y., Boldueva S., Blanco Coronado J. L., Gonzalez Juanatey C., Otero E., Alonso D., Torres Llergo J., Gonzalez Lama J., De Prada Tiffe J. A. V., Garcia Seara F. J., Gomez Doblas J. J., Riancho J. A., Clua-Espuny J. L., Motero J., Arrarte V. I., Martin Raymondi D., Isasti Aizpurua G., Marin F., Nieto J. A., Fernandez Portales J., Alvarez Garcia P., Torstensson I., Cederin B., Kalm T., Rosenqvist U., Thulin J., Hajimirsadeghi A., Crisby M., Manoj A., Bakhai A., Mistri A., Krishnan M., Kumar S., Kirubakaran S., Thomas H., Camm J., Ahmed F., Ross A. M., Barry K., Stockwell R., Broadley A., Mamun M., Chatterjee K., Cooke J., McCready J., Dutta D., John K., Pandya P., Howlett R., Vinson P., Foley P., Bruce D., Dixit A., Broughton D., Taylor J., Schilling R., Leon K., Saeed K., Shaheen S., Tawfik M., Mortadda A., Seleem M., Aly M. S. I., Kazamel G., Elbadry M., Kamal S., Hassan M., Mostafa M., Medhat M. E. S., Ghaleb R., Taha M. O., Daoud I., Al Din H., Imam A. M., El Hameed M. A., Al-Murayeh M., Akhtar N., Matto B. M., Ghani M. A., Amoudi O. A., Morsy M. M., Bashir A. A. F., Al Hossni Y. M., Al Ghamdi B., Mir S., Dardir D., Masswary A., Al Shehri A. R., Iqbal J., Almansori M. A. J., Venkitachalam C. G., Kurian J., Rao J., Aisheh A., Albawab A. A., Subbaraman B., Amanat A., Esfehani K. J., Lochan R., Bin Brek A., Mittal B., Ghazi Y., Krishna M., Tabatabaei S. B., Thoppil P. S., Nasim S., El Khider Nour S., Barros P., Almeida A. P., Andrade M., Garbelini B., Silvestrini T. L., Alves A. R., De Lima C. E. B., Kormann A., De Lima G. G., Halperin C., Salvadori Junior D., Freitas A. F., Gemelli J. R., Ornelas C. E., Dantas J. M. M., Aziz J. L., Backes L. M., Barroso W. S., Paiva M. S., De Figueiredo Neto J. A., Dos Santos F. R., De Lima Neto J. A., Bergo R., Salvador Junior P. R., Lopez A. G., Alva J. C. P., Gamba M. A. A., Padilla-Padilla F. G., Ruiz A. E. B., Berlingieri J., Bakbak A., Gupta M., Saunders K., Costa-Vitali A., Beaudry P. R., Bhargava R., Khaykin Y., Healey J. S., Crystal E., Nadeau Dhillon, Begg A., Anderson C., Baveja S., Cross D., Catanchin A., Brieger D., Lim K. T., Davidson P., Tan R., Bhindi R., Hickey J., Layland J., Bloch M., Itty C., Singh B., Carroll P., Lee A., Starmer G., and Lehman R.

Abstract

Background: Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. Methods and results: Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet the

Published
2019

8. Heart Rate Recovery After Exercise Is Associated With Arrhythmic Events in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

Author

Lieve, KVV, Dusi, V, v.d. Werf, C, Bos, JM, Lane, CM, Stokke, MK, Roston, TM, Djupsjöbacka, A, Wada, Y, Denjoy, I, Bundgaard, H, Noguer, FRI, Semsarian, C, Robyns, T, Hofman, N, Tanck, MW, van den Berg, M P, Kammeraad, Janneke, Krahn, AD, Clur, SAB, Sacher, F, Till, J, Skinner, JR, Tfelt-Hansen, J, Probst, V, Leenhardt, A, Horie, M, Swan, H, Roberts, JD, Sanatani, S, Haugaa, KH, Schwartz, PJ, Ackerman, MJ, Wilde, AA, Lieve, KVV, Dusi, V, v.d. Werf, C, Bos, JM, Lane, CM, Stokke, MK, Roston, TM, Djupsjöbacka, A, Wada, Y, Denjoy, I, Bundgaard, H, Noguer, FRI, Semsarian, C, Robyns, T, Hofman, N, Tanck, MW, van den Berg, M P, Kammeraad, Janneke, Krahn, AD, Clur, SAB, Sacher, F, Till, J, Skinner, JR, Tfelt-Hansen, J, Probst, V, Leenhardt, A, Horie, M, Swan, H, Roberts, JD, Sanatani, S, Haugaa, KH, Schwartz, PJ, Ackerman, MJ, and Wilde, AA

Published
2020

9. International Triadin Knockout Syndrome Registry: The Clinical Phenotype and Treatment Outcomes of Patients with Triadin Knockout Syndrome

Author

Clemens, D, Tester, D, Giudicessi, J, Bos, J, Rohatgi, R, Abrams, D, Balaji, S, Crotti, L, Faure, J, Napolitano, C, Priori, S, Probst, V, Rooryck-Thambo, C, Roux-Buisson, N, Sacher, F, Schwartz, P, Silka, M, Walsh, M, Ackerman, M, Clemens, DJ, Tester, DJ, Giudicessi, JR, Bos, JM, Rohatgi, RK, Abrams, DJ, Priori, SG, Schwartz, PJ, Silka, MJ, Walsh, MA, Ackerman, MJ, Clemens, D, Tester, D, Giudicessi, J, Bos, J, Rohatgi, R, Abrams, D, Balaji, S, Crotti, L, Faure, J, Napolitano, C, Priori, S, Probst, V, Rooryck-Thambo, C, Roux-Buisson, N, Sacher, F, Schwartz, P, Silka, M, Walsh, M, Ackerman, M, Clemens, DJ, Tester, DJ, Giudicessi, JR, Bos, JM, Rohatgi, RK, Abrams, DJ, Priori, SG, Schwartz, PJ, Silka, MJ, Walsh, MA, and Ackerman, MJ

Abstract

Background: Triadin knockout syndrome (TKOS) is a rare, inherited arrhythmia syndrome caused by recessive null mutations in TRDN-encoded cardiac triadin. Based previously on 5 triadin null patients, TKOS has been characterized by extensive T-wave inversions, transient QT prolongation, and severe disease expression of exercise-induced cardiac arrest in early childhood refractory to conventional therapy. Methods: We have established the International Triadin Knockout Syndrome Registry to include patients who have genetically proven homozygous/compound heterozygous TRDN null mutations. Clinical/genetic data were collected using an online survey generated through REDCap. Results: Currently, the International Triadin Knockout Syndrome Registry includes 21 patients (11 males, average age of 18 years) from 16 families. Twenty patients (95%) presented with either cardiac arrest (15, 71%) or syncope (5, 24%) at an average age of 3 years. Mild skeletal myopathy/proximal muscle weakness was noted in 6 (29%) patients. Of the 19 surviving patients, 16 (84%) exhibit T-wave inversions, and 10 (53%) have transient QT prolongation > 480 ms. Eight of 9 patients had ventricular ectopy on exercise stress testing. Thirteen (68%) patients have received implantable defibrillators. Despite various treatment strategies, 14 (74%) patients have had recurrent breakthrough cardiac events. Conclusion: TKOS is a potentially lethal disease characterized by T-wave inversions in the precordial leads, transient QT prolongation in some, and recurrent ventricular arrhythmias at a young age despite aggressive treatment. Patients displaying this phenotype should undergo TRDN genetic testing as TKOS may be a cause for otherwise unexplained cardiac arrest in young children. As gene therapy advances, enrollment into the International Triadin Knockout Syndrome Registry is encouraged to better understand TKOS and to ready a well-characterized cohort for future TRDN gene therapy trials.

Published
2019

10. International Triadin Knockout Syndrome Registry: The Clinical Phenotype and Treatment Outcomes of Patients with Triadin Knockout Syndrome

Author

Clemens, D, Tester, D, Giudicessi, J, Bos, J, Rohatgi, R, Abrams, D, Balaji, S, Crotti, L, Faure, J, Napolitano, C, Priori, S, Probst, V, Rooryck-Thambo, C, Roux-Buisson, N, Sacher, F, Schwartz, P, Silka, M, Walsh, M, Ackerman, M, Clemens, DJ, Tester, DJ, Giudicessi, JR, Bos, JM, Rohatgi, RK, Abrams, DJ, Priori, SG, Schwartz, PJ, Silka, MJ, Walsh, MA, Ackerman, MJ, Clemens, D, Tester, D, Giudicessi, J, Bos, J, Rohatgi, R, Abrams, D, Balaji, S, Crotti, L, Faure, J, Napolitano, C, Priori, S, Probst, V, Rooryck-Thambo, C, Roux-Buisson, N, Sacher, F, Schwartz, P, Silka, M, Walsh, M, Ackerman, M, Clemens, DJ, Tester, DJ, Giudicessi, JR, Bos, JM, Rohatgi, RK, Abrams, DJ, Priori, SG, Schwartz, PJ, Silka, MJ, Walsh, MA, and Ackerman, MJ

Abstract

Background: Triadin knockout syndrome (TKOS) is a rare, inherited arrhythmia syndrome caused by recessive null mutations in TRDN-encoded cardiac triadin. Based previously on 5 triadin null patients, TKOS has been characterized by extensive T-wave inversions, transient QT prolongation, and severe disease expression of exercise-induced cardiac arrest in early childhood refractory to conventional therapy. Methods: We have established the International Triadin Knockout Syndrome Registry to include patients who have genetically proven homozygous/compound heterozygous TRDN null mutations. Clinical/genetic data were collected using an online survey generated through REDCap. Results: Currently, the International Triadin Knockout Syndrome Registry includes 21 patients (11 males, average age of 18 years) from 16 families. Twenty patients (95%) presented with either cardiac arrest (15, 71%) or syncope (5, 24%) at an average age of 3 years. Mild skeletal myopathy/proximal muscle weakness was noted in 6 (29%) patients. Of the 19 surviving patients, 16 (84%) exhibit T-wave inversions, and 10 (53%) have transient QT prolongation > 480 ms. Eight of 9 patients had ventricular ectopy on exercise stress testing. Thirteen (68%) patients have received implantable defibrillators. Despite various treatment strategies, 14 (74%) patients have had recurrent breakthrough cardiac events. Conclusion: TKOS is a potentially lethal disease characterized by T-wave inversions in the precordial leads, transient QT prolongation in some, and recurrent ventricular arrhythmias at a young age despite aggressive treatment. Patients displaying this phenotype should undergo TRDN genetic testing as TKOS may be a cause for otherwise unexplained cardiac arrest in young children. As gene therapy advances, enrollment into the International Triadin Knockout Syndrome Registry is encouraged to better understand TKOS and to ready a well-characterized cohort for future TRDN gene therapy trials.

Published
2019

11. Multicenter Experience With Catheter Ablation for Ventricular Tachycardia in Lamin A/C Cardiomyopathy

Author

Kumar, S, Androulakis, AFA, Sellal, J-M, Maury, P, Gandjbakhch, E, Waintraub, X, Rollin, A, Richard, P, Charron, P, Baldinger, SH, Macintyre, CJ, Koplan, BA, John, RM, Michaud, GF, Zeppenfeld, K, Sacher, F, Lakdawala, NK, Stevenson, WG, Tedrow, UB, Kumar, S, Androulakis, AFA, Sellal, J-M, Maury, P, Gandjbakhch, E, Waintraub, X, Rollin, A, Richard, P, Charron, P, Baldinger, SH, Macintyre, CJ, Koplan, BA, John, RM, Michaud, GF, Zeppenfeld, K, Sacher, F, Lakdawala, NK, Stevenson, WG, and Tedrow, UB

Abstract

BACKGROUND: Lamin A/C (LMNA) cardiomyopathy is a genetic disease with a proclivity for ventricular arrhythmias. We describe the multicenter experience with percutaneous catheter ablation of sustained monomorphic ventricular tachycardia (VT) in LMNA cardiomyopathy. METHODS AND RESULTS: Twenty-five consecutive LMNA mutation patients from 4 centers were included (mean age, 55±9 years; ejection fraction, 34±12%; VT storm in 36%). Complete atrioventricular block was present in 11 patients; 3 patients were on mechanical circulatory support for severe heart failure. A median of 3 VTs were inducible per patient; in 82%, mapping was consistent with origin from scar in the basal left ventricle, particularly the septum, but also basal inferior wall and subaortic mitral continuity. After multiple procedures (median 2/patient; transcoronary alcohol in 6 and surgical cryoablation in 2 patients), acute success (noninducibility of any VT) was achieved in only 25% of patients. Partial success (inducibility of a nonclinical VT only: 50%) and failure (persistent inducibility of clinical VT: 12.5%) was attributed to intramural septal substrate in 13 of 18 patients (72%). Complications occurred in 25% of patients. After a median follow-up of 7 months after the last procedure, 91% experienced ≥1 VT recurrence, 44% received or were awaiting mechanical circulatory support or transplant for end-stage heart failure, and 26% died. CONCLUSIONS: Catheter ablation of VT associated with LMNA cardiomyopathy is associated with poor outcomes including high rate of arrhythmia recurrence, progression to end-stage heart failure, and high mortality. Basal septal scar and intramural VT origin makes VT ablation challenging in this population.

Published
2016

12. Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers

Author

Kumar, S, Baldinger, SH, Gandjbakhch, E, Maury, P, Sellal, J-M, Androulakis, AFA, Waintraub, X, Charron, P, Rollin, A, Richard, P, Stevenson, WG, Macintyre, CJ, Ho, CY, Thompson, T, Vohra, JK, Kalman, JM, Zeppenfeld, K, Sacher, F, Tedrow, UB, Lakdawala, NK, Kumar, S, Baldinger, SH, Gandjbakhch, E, Maury, P, Sellal, J-M, Androulakis, AFA, Waintraub, X, Charron, P, Rollin, A, Richard, P, Stevenson, WG, Macintyre, CJ, Ho, CY, Thompson, T, Vohra, JK, Kalman, JM, Zeppenfeld, K, Sacher, F, Tedrow, UB, and Lakdawala, NK

Abstract

BACKGROUND: Mutations in LMNA are variably expressed and may cause cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and ventricular arrhythmias (VA). Detailed natural history studies of LMNA-associated arrhythmic and nonarrhythmic outcomes are limited, and the prognostic significance of the index cardiac phenotype remains uncertain. OBJECTIVES: This study sought to describe the arrhythmic and nonarrhythmic outcomes of LMNA mutation carriers and to assess the prognostic significance of the index cardiac phenotype. METHODS: The incidence of AVB, AA, sustained VA, left ventricular systolic dysfunction (LVD) (= left ventricular ejection fraction ≤50%), and end-stage heart failure (HF) was retrospectively determined in 122 consecutive LMNA mutation carriers followed at 5 referral centers for a median of 7 years from first clinical contact. Predictors of VA and end-stage HF or death were determined. RESULTS: The prevalence of clinical manifestations increased broadly from index evaluation to median follow-up: AVB, 46% to 57%; AA, 39% to 63%; VA, 16% to 34%; and LVD, 44% to 57%. Implantable cardioverter-defibrillators were placed in 59% of patients for new LVD or AVB. End-stage HF developed in 19% of patients, and 13% died. In patients without LVD at presentation, 24% developed new LVD, and 7% developed end-stage HF. Male sex (p = 0.01), nonmissense mutations (p = 0.03), and LVD at index evaluation (p = 0.004) were associated with development of VA, whereas LVD was associated with end-stage HF or death (p < 0.001). Mode of presentation (with isolated or combination of clinical features) did not predict sustained VA or end-stage HF or death. CONCLUSIONS: LMNA-related heart disease was associated with a high incidence of phenotypic progression and adverse arrhythmic and nonarrhythmic events over long-term follow-up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis and subsequent follow-up, including anticipatory planning

Published
2016

13. Impact of clinical and genetic findings on the management of young patients with Brugada syndrome

Author

Andorin, A, Behr, E, Denjoy, I, Crotti, L, Dagradi, F, Jesel, L, Sacher, F, Petit, B, Mabo, P, Maltret, A, Wong, L, Degand, B, Bertaux, G, Maury, P, Dulac, Y, Delasalle, B, Gourraud, J, Babuty, D, Blom, N, Schwartz, P, Wilde, A, Probst, V, Behr, ER, Wong, Lc, Gourraud, JB, Blom, NA, Schwartz, PJ, Wilde, AA, Andorin, A, Behr, E, Denjoy, I, Crotti, L, Dagradi, F, Jesel, L, Sacher, F, Petit, B, Mabo, P, Maltret, A, Wong, L, Degand, B, Bertaux, G, Maury, P, Dulac, Y, Delasalle, B, Gourraud, J, Babuty, D, Blom, N, Schwartz, P, Wilde, A, Probst, V, Behr, ER, Wong, Lc, Gourraud, JB, Blom, NA, Schwartz, PJ, and Wilde, AA

Abstract

Background Brugada syndrome (BrS) is an arrhythmogenic disease associated with sudden cardiac death (SCD) that seldom manifests or is recognized in childhood. Objectives The objectives of this study were to describe the clinical presentation of pediatric BrS to identify prognostic factors for risk stratification and to propose a data-based approach management. Methods We studied 106 patients younger than 19 years at diagnosis of BrS enrolled from 16 European hospitals. Results At diagnosis, BrS was spontaneous (n = 36, 34%) or drug-induced (n = 70, 66%). The mean age was 11.1 ± 5.7 years, and most patients were asymptomatic (family screening, (n = 67, 63%; incidental, n = 13, 12%), while 15 (14%) experienced syncope, 6(6%) aborted SCD or symptomatic ventricular tachycardia, and 5 (5%) other symptoms. During follow-up (median 54 months), 10 (9%) patients had life-threatening arrhythmias (LTA), including 3 (3%) deaths. Six (6%) experienced syncope and 4 (4%) supraventricular tachycardia. Fever triggered 27% of LTA events. An implantable cardioverter-defibrillator was implanted in 22 (21%), with major adverse events in 41%. Of the 11 (10%) patients treated with hydroquinidine, 8 remained asymptomatic. Genetic testing was performed in 75 (71%) patients, and SCN5A rare variants were identified in 58 (55%); 15 of 32 tested probands (47%) were genotype positive. Nine of 10 patients with LTA underwent genetic testing, and all were genotype positive, whereas the 17 SCN5A-negative patients remained asymptomatic. Spontaneous Brugada type 1 electrocardiographic (ECG) pattern (P =.005) and symptoms at diagnosis (P =.001) were predictors of LTA. Time to the first LTA event was shorter in patients with both symptoms at diagnosis and spontaneous Brugada type 1 ECG pattern (P =.006). Conclusion Spontaneous Brugada type 1 ECG pattern and symptoms at diagnosis are predictors of LTA events in the young affected by BrS. The management of BrS should become age-specific, and prevention of

Published
2016

14. Selection of organic process and source indicator substances for the anthropogenically influenced water cycle

Author

Jekel, M., Dott, W., Bergmann, A., Dünnbier, U., Gnirß, R., Haist-Gulde, B., Hamscher, G., Letzel, M., Licha, T., Lyko, S., Miehe, U., Sacher, F., Scheurer, M., Schmidt, C.K., Reemtsma, Thorsten, Ruhl, A.S., Jekel, M., Dott, W., Bergmann, A., Dünnbier, U., Gnirß, R., Haist-Gulde, B., Hamscher, G., Letzel, M., Licha, T., Lyko, S., Miehe, U., Sacher, F., Scheurer, M., Schmidt, C.K., Reemtsma, Thorsten, and Ruhl, A.S.

Abstract

An increasing number of organic micropollutants (OMP) is detected in anthropogenically influenced water cycles. Source control and effective natural and technical barriers are essential to maintain a high quality of drinking water resources under these circumstances. Based on the literature and our own research this study proposes a limited number of OMP that can serve as indicator substances for the major sources of OMP, such as wastewater treatment plants, agriculture and surface runoff. Furthermore functional indicators are proposed that allow assessment of the proper function of natural and technical barriers in the aquatic environment, namely conventional municipal wastewater treatment, advanced treatment (ozonation, activated carbon), bank filtration and soil aquifer treatment as well as self-purification in surface water. These indicator substances include the artificial sweetener acesulfame, the anti-inflammatory drug ibuprofen, the anticonvulsant carbamazepine, the corrosion inhibitor benzotriazole and the herbicide mecoprop among others. The chemical indicator substances are intended to support comparisons between watersheds and technical and natural processes independent of specific water cycles and to reduce efforts and costs of chemical analyses without losing essential information.

Published
2015

15. Impact of patent foramen ovale on left atrial linear lesions in the context of atrial fibrillation ablation

Author

UCL - (MGD) Service de cardiologie, Miyazaki, S., Shah, A.J., Nault, I., Wright, M., Jadidi, A.S., Forclaz, A., Liu, Xingpeng, Linton, N., Xhaet, Olivier, Rivard, L., Derval, N., Sacher, F., Hocini, M., Jaïs, P., Haïssaguerre, M., UCL - (MGD) Service de cardiologie, Miyazaki, S., Shah, A.J., Nault, I., Wright, M., Jadidi, A.S., Forclaz, A., Liu, Xingpeng, Linton, N., Xhaet, Olivier, Rivard, L., Derval, N., Sacher, F., Hocini, M., Jaïs, P., and Haïssaguerre, M.

Abstract

Impact of PFO on LA Linear Ablation. Introduction: We investigated the impact of the mode of left atrial (LA) access via patent foramen ovale (PFO) versus transseptal (TS) puncture on LA linear lesions during atrial fibrillation (AF) ablation. Methods and Results: We investigated 139 (PFO: 25) consecutive patients who underwent mitral isthmus (MI) and/or LA roof linear ablation. Technical endpoint was completeness of linear lesions and duration of radiofrequency (RF) application. During the initial procedure, complete MI and LA roof blocks were created in 13 of 19 (68%) and 14 of 17 (82%) patients in the PFO group, and in 57 of 94 (61%) and 54 of 70 (74%) patients in the TS group, respectively (P = NS). There was no significant difference in RF durations at MI (11.1 ± 8.9 and 15.1 ± 7.6 minutes, P = 0.11), and LA roof (10.1 ± 3.5 and 8.3 ± 5.0 minutes, P = 0.21) between the 2 groups. Among 28 patients who underwent repeat linear ablation, complete MI and LA roof blocks were created in 3 of 4 (75%) and 0 of 1 (0%) patients in the PFO group, and in 16 of 21 (76%) and 7 of 10 (70%) patients in the TS group, respectively (P = NS). There was no significant difference in RF durations at MI (15.3 ± 8.3 and 19.5 ± 18.3 minutes, P = 0.71), and LA roof (19.0 and 10.3 ± 5.4 minutes, P = 0.19) between the 2 groups. Clinical outcomes at 12 months were also similar. Conclusion: There were no significant differences in the procedural success rates, durations of RF application, 12-month clinical outcomes, and complication rates of LA linear ablation between the PFO and TS groups. Accessing the LA via a PFO is not an unfavorable approach toward LA linear ablation. © 2011 Wiley Periodicals, Inc.

Published
2011

16. Preprocedural clinical parameters determining perimitral conduction time during mitral isthmus line ablation

Author

UCL - (MGD) Service de cardiologie, Miyazaki, S., Shah, A.J., Liu, Xingpeng, Jadidi, A.S., Nault, I., Wright, M., Forclaz, A., Linton, N., Xhaet, Olivier, Rivard, L., Derval, N., Knecht, S., Sacher, F., Hocini, M., Jaïs, P., Haïssaguerre, M., UCL - (MGD) Service de cardiologie, Miyazaki, S., Shah, A.J., Liu, Xingpeng, Jadidi, A.S., Nault, I., Wright, M., Forclaz, A., Linton, N., Xhaet, Olivier, Rivard, L., Derval, N., Knecht, S., Sacher, F., Hocini, M., Jaïs, P., and Haïssaguerre, M.

Abstract

Background-Achievement of complete conduction block across left mitral isthmus (MI) is challenging. Anticipation of perimitral conduction time (PMCT) associated with MI block may expedite this procedure. We evaluated the relationship between the preprocedural variables and the quantum of PMCT in patients with bidirectionally blocked MI. Methods and Results-We reviewed clinical and echocardiographic parameters in 290 consecutive patients with confirmed bidirectional MI block during atrial fibrillation (AF) ablation. PMCT was defined as the temporal delay to the latest of the double potentials on the line of block while pacing posteroseptal to it in the left atrium (LA). LA size and type of AF significantly influenced PMCT in multivariate analysis. A cumulative score based on LA size (0≦45 mm; 1>45 mm) and type of AF (0: paroxysmal; 1=nonparoxysmal) ranged from 0 to 2. PMCT was directly correlated to the cumulative score (0: 169 ms; n=78; 95% confidential interval, 156 to 181); 1: 187 ms; n=103; 95% confidential interval, 178 to 196; 2: 209 ms; n=109; 95% confidential interval, 200 to 217). In 61 patients who underwent AF ablation twice, the difference between 2 PMCT values was <30 ms in 75% patients. Another consecutive 143 patients with and without MI block after at least 15 minutes of radiofrequency application were analyzed. Perimitral conduction delay <130 ms ruled out bidirectional MI block. Perimitral conduction delay >173 ms predicted bidirectional block with an accuracy of 86%. Conclusions-LA size and AF type significantly influence PMCT in patients undergoing successful MI ablation. These parameters can be used to predict the time value associated with MI block, preprocedurally. © 2011 American Heart Association, Inc.

Published
2011

17. Inter-laboratory exercise on steroid estrogens in aqueous samples

Author

Heath, E., Kosjek, T., Andersen, H. R., Luetzhoft, H.-C. Holten, Adolfson-Erici, Margaretha, Coquery, M., Duering, R. -A, Gans, O., Guignard, C., Karlsson, P., Manciot, F., Moldovan, Z., Patureau, D., Cruceru, L., Sacher, F., Ledin, A., Heath, E., Kosjek, T., Andersen, H. R., Luetzhoft, H.-C. Holten, Adolfson-Erici, Margaretha, Coquery, M., Duering, R. -A, Gans, O., Guignard, C., Karlsson, P., Manciot, F., Moldovan, Z., Patureau, D., Cruceru, L., Sacher, F., and Ledin, A.

Abstract

An inter-laboratory comparison exercise was organized among European laboratories, under the aegis of EU COST Action 636: ""Xenobiotics in Urban Water Cycle"" The objective was to evaluate the performance of testing laboratories determining ""Endocrine Disrupting Compounds"" (EDC) in various aqueous matrices. As the main task three steroid estrogens. 17 alpha-ethinylestradiol, 17 beta-estradiol and estrone were determined in four spiked aqueous matrices' tap water, river water and wastewater treatment plant influent and effluent using GC-MS and LC-MS/MS Results were compared and discussed according to the analytical techniques applied, the accuracy and reproducibility of the analytical methods and the nature of the sample matrices. Overall, the results obtained in this inter-laboratory exercise reveal a high level of competence among the participating laboratories for the detection of steroid estrogens in water samples indicating that GC-MS as well as LC-MS/MS can equally be employed for the analysis of natural and synthetic hormones., authorCount :16

Published
2010
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18. Management of atrial fibrillation.

Author

UCL - (MGD) Service de cardiologie, Shah, A.J., Jadidi, A.S., Miyazaki, S., Xhaet, Olivier, Linton, N., Scherr, D., Liu, Xingpeng, Forclaz, A., Nault, I., Rivard, L., Derval, N., Sacher, F., Bordachar, P., Ritter, P., Hocini, M., Jais, P., Haissaguerre, Michel, UCL - (MGD) Service de cardiologie, Shah, A.J., Jadidi, A.S., Miyazaki, S., Xhaet, Olivier, Linton, N., Scherr, D., Liu, Xingpeng, Forclaz, A., Nault, I., Rivard, L., Derval, N., Sacher, F., Bordachar, P., Ritter, P., Hocini, M., Jais, P., and Haissaguerre, Michel

Abstract

Atrial fibrillation (AF) is the most common heart rhythm problem and a leading cause of morbidity and mortality. Serious complications associated with this disorder include cardioembolic stroke, heart failure, and death. The worldwide prevalence of AF is rapidly increasing owing to aging of the population. Abnormal impulse formation in the pulmonary veins is known to trigger paroxysmal AF and radiofrequency isolation of these veins is recommended in drug-refractory AF. Active pharmacological research is directed towards selectively targeting the culprit venous cells. Persistent AF is more likely to be an atrial disease. Intrinsic and extrinsic stressors are believed to cause electrostructural alterations in the atrial tissue leading to profibrillatory state. Further research will elucidate the role of stressors and help develop biomarkers to guide early management of AF. An ideal therapy for AF aims at prevention of onset and progression of AF and reduction of AF-related symptoms, hospitalization, stroke, and mortality.

Published
2010

19. Comparison of five in vitro bioassays to measure estrogenic activity in environmental waters

Author

Leusch, FDL, De Jager, C, Levi, Y, Lim, R, Puijker, L, Sacher, F, Tremblay, LA, Wilson, VS, Chapman, HF, Leusch, FDL, De Jager, C, Levi, Y, Lim, R, Puijker, L, Sacher, F, Tremblay, LA, Wilson, VS, and Chapman, HF

Abstract

Bioassays are well established in the pharmaceutical industry and single compound analysis, but there is still uncertainty about their usefulness in environmental monitoring. We compared the responses of five bioassays designed to measure estrogenic activity (the yeast estrogen screen, ER-CALUX, MELN, T47D-KBluc, and E-SCREEN assays) and chemical analysis on extracts from four different water sources (groundwater, raw sewage, treated sewage, and river water). All five bioassays displayed similar trends and there was good agreement with analytical chemistry results. The data from the ER-CALUX and E-SCREEN bioassays were robust and predictable, and well-correlated with predictions from chemical analysis. The T47D-KBluc appeared likewise promising, but with a more limited sample size it was less compelling. The YES assay was less sensitive than the other assays by an order of magnitude, which resulted in a larger number of nondetects. The MELN assay was less predictable, although the possibility that this was due to laboratory-specific difficulties cannot be discounted. With standardized bioassay data analysis and consistency of operating protocols, bioanalytical tools are a promising advance in the development of a tiered approach to environmental water quality monitoring. © 2010 American Chemical Society.

Published
2010

20. Comparison of five in vitro bioassays to measure estrogenic activity in environmental waters

Author

Leusch, FDL, De Jager, C, Levi, Y, Lim, R, Puijker, L, Sacher, F, Tremblay, LA, Wilson, VS, Chapman, HF, Leusch, FDL, De Jager, C, Levi, Y, Lim, R, Puijker, L, Sacher, F, Tremblay, LA, Wilson, VS, and Chapman, HF

Abstract

Bioassays are well established in the pharmaceutical industry and single compound analysis, but there is still uncertainty about their usefulness in environmental monitoring. We compared the responses of five bioassays designed to measure estrogenic activity (the yeast estrogen screen, ER-CALUX, MELN, T47D-KBluc, and E-SCREEN assays) and chemical analysis on extracts from four different water sources (groundwater, raw sewage, treated sewage, and river water). All five bioassays displayed similar trends and there was good agreement with analytical chemistry results. The data from the ER-CALUX and E-SCREEN bioassays were robust and predictable, and well-correlated with predictions from chemical analysis. The T47D-KBluc appeared likewise promising, but with a more limited sample size it was less compelling. The YES assay was less sensitive than the other assays by an order of magnitude, which resulted in a larger number of nondetects. The MELN assay was less predictable, although the possibility that this was due to laboratory-specific difficulties cannot be discounted. With standardized bioassay data analysis and consistency of operating protocols, bioanalytical tools are a promising advance in the development of a tiered approach to environmental water quality monitoring. © 2010 American Chemical Society.

Published
2010

21. Gene expression analysis in zebrafish embryos: a potential approach to predict effect concentrations in the early life stage test

Author

Weil, M., Scholz, Stefan, Zimmer, M., Sacher, F., Duis, K., Weil, M., Scholz, Stefan, Zimmer, M., Sacher, F., and Duis, K.

Abstract

Based on the hypothesis that analysis of gene expression could be used to predict chronic fish toxicity, the zebrafish (Danio rerio) embryo test (DarT), developed as a replacement method for the acute fish test, was expanded to a gene expression D. rerio embryo test (Gene-DarT). The effects of 14 substances on lethal and sublethal endpoints of the DarT and on expression of potential marker genes were investigated: the aryl hydrocarbon receptor 2, cytochrome P450 1A (cyp1a), heat shock protein 70, fizzy-related protein 1, the transcription factors v-maf usculoaponeurotic fibrosarcoma oncogene family protein g (avian) 1 and NF-E2-p45-related factor, and heme oxygenase 1 (hmox1). After exposure of zebrafish embryos for 48 h, differential gene expression was evaluated using reverse transcriptase-polymerase chain reaction, gel electrophoresis, and densitometric analysis of the gels. All tested compounds significantly affected the expression of at least one potential marker gene, with cyp1a and hmox1 being most sensitive. Lowestobserved-effect concentrations (LOECs) for gene expression were below concentrations resulting in 10% lethal effects in the DarT. For 10 (3,4- and 3,5-dichloroaniline, 1,4-dichlorobenzene, 2,4-dinitrophenol, atrazine, parathion-ethyl, chlorotoluron, genistein, 4-nitroquinoline-1-oxide, and cadmium) out of the 14 tested substances, LOEC values derived with the Gene-DarT differ by a factor of less than 10 from LOEC values of fish early life stage tests with zebrafish. For pentachloroaniline and pentachlorobenzene, the Gene-DarT showed a 23- and 153-fold higher sensitivity, respectively, while for lindane, it showed a 13-fold lower sensitivity. For ivermectin, the Gene-DarT was by a factor of more than 1,000 less sensitive than the acute fish test. The results of the present study indicate that gene expression analysis in zebrafish embryos could principally be used to predict effect concentrations in the fish early life stage test.

Published
2009

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