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2. Improving usual care after sudden death in the young with focus on inherited cardiac diseases (the CAREFUL study): a community-based intervention study

Author

van der Werf, Christian, Hendrix, Anneke, Birnie, Erwin, Bots, Michiel L., Vink, Aryan, Bardai, Abdennasser, Blom, Marieke T., Bosch, Jan, Bruins, Wendy, Das, C. (Kees), Koster, Rudolph W., Naujocks, Tatjana, Schaap, Balthasar, Tan, Hanno L., de Vos, Ronald, de Vries, Philip, Woonink, Frits, Doevendans, Pieter A., van Weert, Henk C., Wilde, Arthur A.M., Mosterd, Arend, and van Langen, Irene M.

Published
2016
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10. Sudden cardiac arrest in people with epilepsy in the community

Author

Lamberts, Robert J., Blom, Marieke T., Wassenaar, Merel, Bardai, Abdennasser, Leijten, Frans S., De Haan, Gerrit Jan, Sander, Josemir W., Thijs, Roland D., Tan, Hanno L., and Cardiology

Abstract

Objective: To ascertain whether characteristics of ventricular tachycardia/fibrillation (VT/VF) differed between people with epilepsy and those without and which individuals with epilepsy were at highest risk. Methods: We ascertained 18 people with active epilepsy identified in a community-based registry of sudden cardiac arrest (SCA) with ECG-confirmed VT/VF (cases). We compared them with 470 individuals with VT/VF without epilepsy (VT/VF controls) and 54 individuals with epilepsy without VT/VF (epilepsy controls). Data on comorbidity, epilepsy severity, and medication use were collected and entered into (conditional) logistic regression models to identify determinants of VT/VF in epilepsy. Results: In most cases, there was an obvious (10/18) or presumed cardiovascular cause (5/18) in view of preexisting heart disease. In 2 of the 3 remaining events, near-sudden unexpected death in epilepsy (SUDEP) was established after successful resuscitation. Cases had a higher prevalence of congenital/inherited heart disease (17% vs 1%, p 0.002), and experienced VT/VF at younger age (57 vs 64 years, p 0.023) than VT/VF controls. VT/VF in cases occurred more frequently at/near home (89% vs 58%, p 0.009), and was less frequently witnessed (72% vs 89%, p 0.048) than in VT/VF controls. Cases more frequently had clinically relevant heart disease (50% vs 15%, p 0.005) and intellectual disability (28% vs 1%, p < 0.001) than epilepsy controls. Conclusion: Cardiovascular disease rather than epilepsy characteristics is the main determinant of VT/VF in people with epilepsy in the community. SCA and SUDEP are partially overlapping disease entities.

Published
2015

11. Improving usual care after sudden death in the young with focus on inherited cardiac diseases (the CAREFUL study): A community-based intervention study

Author

Aios en Stafsecr. Cardiologie, General Practice & Nursing Science, Other research (not in main researchprogram), Genetica, Geboortecentrum voorzitterschap, Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Pathologie patiënten zorg, Regenerative Medicine and Stem Cells, DHS-Medisch, Cardiovasculaire Immunologie, Van Der Werf, Christian, Hendrix, Anneke, Birnie, Erwin, Bots, Michiel L., Vink, Aryan, Bardai, Abdennasser, Blom, Marieke T., Bosch, Jan, Bruins, Wendy, Das, C., Koster, Rudolph W., Naujocks, Tatjana, Schaap, Balthasar, Tan, Hanno L., De Vos, Ronald, De Vries, Philip, Woonink, Frits, Doevendans, Pieter A., Van Weert, Henk C., Wilde, Arthur A M, Mosterd, Arend, Van Langen, Irene M., Aios en Stafsecr. Cardiologie, General Practice & Nursing Science, Other research (not in main researchprogram), Genetica, Geboortecentrum voorzitterschap, Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Pathologie patiënten zorg, Regenerative Medicine and Stem Cells, DHS-Medisch, Cardiovasculaire Immunologie, Van Der Werf, Christian, Hendrix, Anneke, Birnie, Erwin, Bots, Michiel L., Vink, Aryan, Bardai, Abdennasser, Blom, Marieke T., Bosch, Jan, Bruins, Wendy, Das, C., Koster, Rudolph W., Naujocks, Tatjana, Schaap, Balthasar, Tan, Hanno L., De Vos, Ronald, De Vries, Philip, Woonink, Frits, Doevendans, Pieter A., Van Weert, Henk C., Wilde, Arthur A M, Mosterd, Arend, and Van Langen, Irene M.

Published
2016

12. Sudden Cardiac Arrest and Rare Genetic Variants in the Community

Author

Milano, Annalisa, primary, Blom, Marieke T., additional, Lodder, Elisabeth M., additional, van Hoeijen, Daniel A., additional, Barc, Julien, additional, Koopmann, Tamara T., additional, Bardai, Abdennasser, additional, Beekman, Leander, additional, Lichtner, Peter, additional, van den Berg, Maarten P., additional, Wilde, Arthur A.M., additional, Bezzina, Connie R., additional, and Tan, Hanno L., additional

Published
2016
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13. Reduced pre-hospital and in-hospital survival rates after out-of-hospital cardiac arrest of patients with type-2 diabetes mellitus: An observational prospective community-based study

Author

Sub Pharmacoepidemiology, Sub Pharmacotherapy, Theoretical, Pharmacoepidemiology and Clinical Pharmacology, Van Hoeijen, Daniel A., Blom, Marieke T., Bardai, Abdennasser, Souverein, Patrick C., De Boer, Anthonius, Tan, Hanno L., Sub Pharmacoepidemiology, Sub Pharmacotherapy, Theoretical, Pharmacoepidemiology and Clinical Pharmacology, Van Hoeijen, Daniel A., Blom, Marieke T., Bardai, Abdennasser, Souverein, Patrick C., De Boer, Anthonius, and Tan, Hanno L.

Published
2015

14. Improving usual care after sudden death in the young with focus on inherited cardiac diseases (the CAREFUL study): a community-based intervention study

Author

van der Werf, Christian, primary, Hendrix, Anneke, additional, Birnie, Erwin, additional, Bots, Michiel L., additional, Vink, Aryan, additional, Bardai, Abdennasser, additional, Blom, Marieke T., additional, Bosch, Jan, additional, Bruins, Wendy, additional, Das, C. (Kees), additional, Koster, Rudolph W., additional, Naujocks, Tatjana, additional, Schaap, Balthasar, additional, Tan, Hanno L., additional, de Vos, Ronald, additional, de Vries, Philip, additional, Woonink, Frits, additional, Doevendans, Pieter A., additional, van Weert, Henk C., additional, Wilde, Arthur A.M., additional, Mosterd, Arend, additional, and van Langen, Irene M., additional

Published
2015
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15. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

Author

Arking, Dan E, Pulit, Sara L, Crotti, Lia, van der Harst, Pim, Munroe, Patricia B, Koopmann, Tamara T, Sotoodehnia, Nona, Rossin, Elizabeth J, Morley, Michael, Wang, Xinchen, Johnson, Andrew D, Lundby, Alicia, Gudbjartsson, Daníel F, Noseworthy, Peter A, Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V, Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M, Nolte, Ilja M, Smith, Albert Vernon, Bis, Joshua C, Isaacs, Aaron, Newhouse, Stephen J, Evans, Daniel S, Post, Wendy S, Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A, Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J, Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W, Naluai, Asa T, Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G, Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A, Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D, Harris, Tamara B, Launer, Lenore J, Shuldiner, Alan R, Alonso, Alvaro, Bader, Joel S, Ehret, Georg, Huang, Hailiang, Kao, W H Linda, Strait, James B, Macfarlane, Peter W, Brown, Morris, Caulfield, Mark J, Samani, Nilesh J, Kronenberg, Florian, Willeit, Johann, Smith, J Gustav, Greiser, Karin H, Meyer Zu Schwabedissen, Henriette, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R, Psaty, Bruce M, Rotter, Jerome I, Kolcic, Ivana, Polašek, Ozren, Wright, Alan F, Griffin, Maura, Daly, Mark J, Arnar, David O, Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C, Roden, Dan M, Zuvich, Rebecca L, Emilsson, Valur, Plump, Andrew S, Larson, Martin G, O'Donnell, Christopher J, Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R, Nalls, Michael A, Jula, Antti, Kontula, Kimmo K, Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M, den Hoed, Marcel, Loos, Ruth J F, Thelle, Dag S, Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F, Waldenberger, Melanie, de Boer, Rudolf A, Franke, Lude, van der Vleuten, Pieter A, Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A M, Behr, Elijah R, Dalageorgou, Chrysoula, Giudicessi, John R, Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M, Scherer, Stephen W, Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E, Greco M, Fabiola Del, Fuchsberger, Christian, O'Connell, Jeffrey R, Lee, Wai K, Watt, Graham C M, Campbell, Harry, Wild, Sarah H, El Mokhtari, Nour E, Frey, Norbert, Asselbergs, Folkert W, Mateo Leach, Irene, Navis, Gerjan, van den Berg, Maarten P, van Veldhuisen, Dirk J, Kellis, Manolis, Krijthe, Bouwe P, Franco, Oscar H, Hofman, Albert, Kors, Jan A, Uitterlinden, André G, Witteman, Jacqueline C M, Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A, Abecasis, Gonçalo R, Lakatta, Edward G, Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R P, Völker, Uwe, Snieder, Harold, Spector, Timothy D, Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T, Viikari, Jorma S, Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N, Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F, Nyberg, Fredrik, Whincup, Peter H, Hingorani, Aroon D, Schott, Jean-Jacques, Bezzina, Connie R, Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F, Rudan, Igor, Franke, Andre, Mühleisen, Thomas W, Pramstaller, Peter P, Lehtimäki, Terho J, Paterson, Andrew D, Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia M, Siscovick, David S, Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B, Sanna, Serena, Ritchie, Marylyn D, Stricker, Bruno H, Stefansson, Kari, Boyer, Laurie A, Cappola, Thomas P, Olsen, Jesper V, Lage, Kasper, Schwartz, Peter J, Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J, Pfeufer, Arne, de Bakker, Paul I W, Newton-Cheh, Christopher, Arking, Dan E, Pulit, Sara L, Crotti, Lia, van der Harst, Pim, Munroe, Patricia B, Koopmann, Tamara T, Sotoodehnia, Nona, Rossin, Elizabeth J, Morley, Michael, Wang, Xinchen, Johnson, Andrew D, Lundby, Alicia, Gudbjartsson, Daníel F, Noseworthy, Peter A, Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V, Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M, Nolte, Ilja M, Smith, Albert Vernon, Bis, Joshua C, Isaacs, Aaron, Newhouse, Stephen J, Evans, Daniel S, Post, Wendy S, Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A, Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J, Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W, Naluai, Asa T, Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G, Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A, Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D, Harris, Tamara B, Launer, Lenore J, Shuldiner, Alan R, Alonso, Alvaro, Bader, Joel S, Ehret, Georg, Huang, Hailiang, Kao, W H Linda, Strait, James B, Macfarlane, Peter W, Brown, Morris, Caulfield, Mark J, Samani, Nilesh J, Kronenberg, Florian, Willeit, Johann, Smith, J Gustav, Greiser, Karin H, Meyer Zu Schwabedissen, Henriette, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R, Psaty, Bruce M, Rotter, Jerome I, Kolcic, Ivana, Polašek, Ozren, Wright, Alan F, Griffin, Maura, Daly, Mark J, Arnar, David O, Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C, Roden, Dan M, Zuvich, Rebecca L, Emilsson, Valur, Plump, Andrew S, Larson, Martin G, O'Donnell, Christopher J, Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R, Nalls, Michael A, Jula, Antti, Kontula, Kimmo K, Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M, den Hoed, Marcel, Loos, Ruth J F, Thelle, Dag S, Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F, Waldenberger, Melanie, de Boer, Rudolf A, Franke, Lude, van der Vleuten, Pieter A, Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A M, Behr, Elijah R, Dalageorgou, Chrysoula, Giudicessi, John R, Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M, Scherer, Stephen W, Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E, Greco M, Fabiola Del, Fuchsberger, Christian, O'Connell, Jeffrey R, Lee, Wai K, Watt, Graham C M, Campbell, Harry, Wild, Sarah H, El Mokhtari, Nour E, Frey, Norbert, Asselbergs, Folkert W, Mateo Leach, Irene, Navis, Gerjan, van den Berg, Maarten P, van Veldhuisen, Dirk J, Kellis, Manolis, Krijthe, Bouwe P, Franco, Oscar H, Hofman, Albert, Kors, Jan A, Uitterlinden, André G, Witteman, Jacqueline C M, Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A, Abecasis, Gonçalo R, Lakatta, Edward G, Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R P, Völker, Uwe, Snieder, Harold, Spector, Timothy D, Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T, Viikari, Jorma S, Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N, Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F, Nyberg, Fredrik, Whincup, Peter H, Hingorani, Aroon D, Schott, Jean-Jacques, Bezzina, Connie R, Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F, Rudan, Igor, Franke, Andre, Mühleisen, Thomas W, Pramstaller, Peter P, Lehtimäki, Terho J, Paterson, Andrew D, Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia M, Siscovick, David S, Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B, Sanna, Serena, Ritchie, Marylyn D, Stricker, Bruno H, Stefansson, Kari, Boyer, Laurie A, Cappola, Thomas P, Olsen, Jesper V, Lage, Kasper, Schwartz, Peter J, Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J, Pfeufer, Arne, de Bakker, Paul I W, and Newton-Cheh, Christopher

Abstract

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Published
2014
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17. Giant T-U waves precede torsades de pointes in long QT syndrome: a systematic electrocardiographic analysis in patients with acquired and congenital QT prolongation

Author

Kirchhof, Paulus, Franz, Michael R., Bardai, Abdennasser, Wilde, Arthur M., Cardiology, and Amsterdam Cardiovascular Sciences

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, ECG, mental disorders, nutritional and metabolic diseases, torsades de pointes, cardiovascular diseases, proarrhythmia, U-wave, nervous system diseases
Abstract

ObjectivesThis study sought to identify electrocardiographic (ECG) criteria that are associated with initiation of torsades de pointes (TdP) in patients with acquired (a-) and congenital (c-) long QT syndrome (LQTS).BackgroundElectrocardiographic criteria used as risk predictors for TdP commonly rely on a prolonged QT interval but rarely consider abnormal T–U waves.MethodsWe analyzed ECG recordings with TdP from 35 LQTS patients (15 c-LQTS and 20 a-LQTS) and compared them with premature ventricular complexes (PVCs) from 40 patients with normal QT intervals and with PVCs in 24 of the 35 LQTS patients not related to TdP.ResultsAbnormal T–U waves (6.2 ± 0.9 mm) directly preceded TdP in 34 of 35 LQTS patients and were larger than T-wave amplitude (2.8 ± 0.2 mm) in control patients and larger than the largest T–U-wave in LQTS without TdP (4.7 ± 0.8 mm). The TdP-initiating beat emerged from a T–U-wave in 27 of 35 LQTS patients and in none of 40 control patients. The QRS duration of the first TdP beat (175 ± 12 ms) was longer than in control PVCs (145 ± 4 ms) and in PVCs in LQTS patients not related to TdP (138 ± 22 ms). The QRS angle was less steep before TdP than in other PVCs (all p < 0.05).ConclusionsAbnormal, giant T–U waves separate TdP initiation in LQTS patients from PVCs in other heart disease and from other PVCs in LQTS patients. These ECG analyses suggest that early afterdepolarizations initiate TdP and, if present, may help to identify an imminent risk for TdP.

Published
2009

21. Trends in survival after out-of-hospital cardiac arrest

Author

Blom, Marieke, primary, Beesems, Stefanie, additional, Homma, Paulien, additional, Zijlstra, Jolanda, additional, van Hoeijen, Daniel, additional, Bardai, Abdennasser, additional, Berdowski, Jocelyn, additional, Tan, Hanno, additional, and Koster, Rudolph, additional

Published
2013
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22. Increased Risk of Sudden Cardiac Arrest in Obstructive Pulmonary Disease: A Case-Control Study

Author

Warnier, Miriam Jacoba, primary, Blom, Marieke Tabo, additional, Bardai, Abdennasser, additional, Berdowksi, Jocelyn, additional, Souverein, Patrick Cyriel, additional, Hoes, Arno Wilhelmus, additional, Rutten, Frans Hendrik, additional, de Boer, Anthonius, additional, Koster, Rudolph Willem, additional, De Bruin, Marie Louise, additional, and Tan, Han Liong, additional

Published
2013
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24. Epilepsy Is a Risk Factor for Sudden Cardiac Arrest in the General Population

Author

Bardai, Abdennasser, primary, Lamberts, Robert J., additional, Blom, Marieke T., additional, Spanjaart, Anne M., additional, Berdowski, Jocelyn, additional, van der Staal, Sebastiaan R., additional, Brouwer, Henk J., additional, Koster, Rudolph W., additional, Sander, Josemir W., additional, Thijs, Roland D., additional, and Tan, Hanno L., additional

Published
2012
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26. A Large Candidate Gene Survey Identifies the KCNE1 D85N Polymorphism as a Possible Modulator of Drug-Induced Torsades de Pointes

Author

Kääb, Stefan, primary, Crawford, Dana C., additional, Sinner, Moritz F., additional, Behr, Elijah R., additional, Kannankeril, Prince J., additional, Wilde, Arthur A.M., additional, Bezzina, Connie R., additional, Schulze-Bahr, Eric, additional, Guicheney, Pascale, additional, Bishopric, Nanette H., additional, Myerburg, Robert J., additional, Schott, Jean-Jacques, additional, Pfeufer, Arne, additional, Beckmann, Britt-Maria, additional, Martens, Eimo, additional, Zhang, Taifang, additional, Stallmeyer, Birgit, additional, Zumhagen, Sven, additional, Denjoy, Isabelle, additional, Bardai, Abdennasser, additional, Van Gelder, Isabelle C., additional, Jamshidi, Yalda, additional, Dalageorgou, Chrysoula, additional, Marshall, Vanessa, additional, Jeffery, Steve, additional, Shakir, Saad, additional, Camm, A. John, additional, Steinbeck, Gerhard, additional, Perz, Siegfried, additional, Lichtner, Peter, additional, Meitinger, Thomas, additional, Peters, Annette, additional, Wichmann, H.-Erich, additional, Ingram, Christiana, additional, Bradford, Yuki, additional, Carter, Shannon, additional, Norris, Kris, additional, Ritchie, Marylyn D., additional, George, Alfred L., additional, and Roden, Dan M., additional

Published
2012
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28. Differential Changes in QTc Duration during In-Hospital Haloperidol Use

Author

Blom, Marieke T., primary, Bardai, Abdennasser, additional, van Munster, Barbara C., additional, Nieuwland, Mei-Ing, additional, de Jong, Hendrik, additional, van Hoeijen, Daniel A., additional, Spanjaart, Anne M., additional, de Boer, Anthonius, additional, de Rooij, Sophia E., additional, and Tan, Hanno L., additional

Published
2011
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29. Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

Author

Arking, Dan E., primary, Junttila, M. Juhani, additional, Goyette, Philippe, additional, Huertas-Vazquez, Adriana, additional, Eijgelsheim, Mark, additional, Blom, Marieke T., additional, Newton-Cheh, Christopher, additional, Reinier, Kyndaron, additional, Teodorescu, Carmen, additional, Uy-Evanado, Audrey, additional, Carter-Monroe, Naima, additional, Kaikkonen, Kari S., additional, Kortelainen, Marja-Leena, additional, Boucher, Gabrielle, additional, Lagacé, Caroline, additional, Moes, Anna, additional, Zhao, XiaoQing, additional, Kolodgie, Frank, additional, Rivadeneira, Fernando, additional, Hofman, Albert, additional, Witteman, Jacqueline C. M., additional, Uitterlinden, André G., additional, Marsman, Roos F., additional, Pazoki, Raha, additional, Bardai, Abdennasser, additional, Koster, Rudolph W., additional, Dehghan, Abbas, additional, Hwang, Shih-Jen, additional, Bhatnagar, Pallav, additional, Post, Wendy, additional, Hilton, Gina, additional, Prineas, Ronald J., additional, Li, Man, additional, Köttgen, Anna, additional, Ehret, Georg, additional, Boerwinkle, Eric, additional, Coresh, Josef, additional, Kao, W. H. Linda, additional, Psaty, Bruce M., additional, Tomaselli, Gordon F., additional, Sotoodehnia, Nona, additional, Siscovick, David S., additional, Burke, Greg L., additional, Marbán, Eduardo, additional, Spooner, Peter M., additional, Cupples, L. Adrienne, additional, Jui, Jonathan, additional, Gunson, Karen, additional, Kesäniemi, Y. Antero, additional, Wilde, Arthur A. M., additional, Tardif, Jean-Claude, additional, O'Donnell, Christopher J., additional, Bezzina, Connie R., additional, Virmani, Renu, additional, Stricker, Bruno H. C. h., additional, Tan, Hanno L., additional, Albert, Christine M., additional, Chakravarti, Aravinda, additional, Rioux, John D., additional, Huikuri, Heikki V., additional, and Chugh, Sumeet S., additional

Published
2011
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30. A Complex Double Deletion in LMNA Underlies Progressive Cardiac Conduction Disease, Atrial Arrhythmias, and Sudden Death

Author

Marsman, Roos F., primary, Bardai, Abdennasser, additional, Postma, Alex V., additional, Res, Jan C.J., additional, Koopmann, Tamara T., additional, Beekman, Leander, additional, van der Wal, Allard C., additional, Pinto, Yigal M., additional, Lekanne Deprez, Ronald H., additional, Wilde, Arthur A.M., additional, Jordaens, Luc J., additional, and Bezzina, Connie R., additional

Published
2011
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31. Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction

Author

Bezzina, Connie R, primary, Pazoki, Raha, additional, Bardai, Abdennasser, additional, Marsman, Roos F, additional, de Jong, Jonas S S G, additional, Blom, Marieke T, additional, Scicluna, Brendon P, additional, Jukema, J Wouter, additional, Bindraban, Navin R, additional, Lichtner, Peter, additional, Pfeufer, Arne, additional, Bishopric, Nanette H, additional, Roden, Dan M, additional, Meitinger, Thomas, additional, Chugh, Sumeet S, additional, Myerburg, Robert J, additional, Jouven, Xavier, additional, Kääb, Stefan, additional, Dekker, Lukas R C, additional, Tan, Hanno L, additional, Tanck, Michael W T, additional, and Wilde, Arthur A M, additional

Published
2010
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35. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author

Arking, Dan E., Pulit, Sara L., Crotti, Lia, van der Harst, Pim, Munroe, Patricia B., Koopmann, Tamara T., Sotoodehnia, Nona, Rossin, Elizabeth J., Morley, Michael, Wang, Xinchen, Johnson, Andrew D., Lundby, Alicia, Gudbjartsson, Daníel F., Noseworthy, Peter A., Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V., Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M., Nolte, Ilja M., Smith, Albert Vernon, Bis, Joshua C., Isaacs, Aaron, Newhouse, Stephen J., Evans, Daniel S., Post, Wendy S., Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A., Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J., Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W., Naluai, Åsa T., Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G., Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A., Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D., Harris, Tamara B., Launer, Lenore J., Shuldiner, Alan R., Alonso, Alvaro, Bader, Joel S., Ehret, Georg, Huang, Hailiang, Kao, W.H. Linda, Strait, James B., Macfarlane, Peter W., Brown, Morris, Caulfield, Mark J., Samani, Nilesh J., Kronenberg, Florian, Willeit, Johann, Smith, J. Gustav, Greiser, Karin H., zu Schwabedissen, Henriette Meyer, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R., Psaty, Bruce M., Rotter, Jerome I., Kolcic, Ivana, Polašek, Ozren, Wright, Alan F., Griffin, Maura, Daly, Mark J., Arnar, David O., Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C., Roden, Dan M., Zuvich, Rebecca L., Emilsson, Valur, Plump, Andrew S., Larson, Martin G., O'Donnell, Christopher J., Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P., Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R., Nalls, Michael A., Jula, Antti, Kontula, Kimmo K., Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M., consortium, HRGEN, den Hoed, Marcel, Loos, Ruth J.F., Thelle, Dag S., Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F., Waldenberger, Melanie, de Boer, Rudolf A., Franke, Lude, van der Vleuten, Pieter A., Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A.M., Behr, Elijah R., Dalageorgou, Chrysoula, Giudicessi, John R., Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M., Scherer, Stephen W., Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E., Fabiola Del, Greco M., Fuchsberger, Christian, O'Connell, Jeffrey R., Lee, Wai K., Watt, Graham C.M., Campbell, Harry, Wild, Sarah H., El Mokhtari, Nour E., Frey, Norbert, Asselbergs, Folkert W., Leach, Irene Mateo, Navis, Gerjan, van den Berg, Maarten P., van Veldhuisen, Dirk J., Kellis, Manolis, Krijthe, Bouwe P., Franco, Oscar H., Hofman, Albert, Kors, Jan A., Uitterlinden, André G., Witteman, Jacqueline C.M., Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A., Abecasis, Gonçalo R., Lakatta, Edward G., Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R.P., Völker, Uwe, Snieder, Harold, Spector, Timothy D., Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T., Viikari, Jorma S., Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N., Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F., Nyberg, Fredrik, Whincup, Peter H., Hingorani, Aroon, Schott, Jean-Jacques, Bezzina, Connie R., Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F., Rudan, Igor, Franke, Andre, Mühleisen, Thomas W., Pramstaller, Peter P., Lehtimäki, Terho J., Paterson, Andrew D., Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia, Siscovick, David S., Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B., Sanna, Serena, Ritchie, Marylyn D., Stricker, Bruno H., Stefansson, Kari, Boyer, Laurie A., Cappola, Thomas P., Olsen, Jesper V., Lage, Kasper, Schwartz, Peter J., Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J., Pfeufer, Arne, de Bakker, Paul I.W., and Newton-Cheh, Christopher

Subjects
genome-wide association study, QT interval, Long QT Syndrome, sudden cardiac death, myocardial repolarization, arrhythmias
Abstract

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal Mendelian Long QT Syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals we identified 35 common variant QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies novel candidate genes for ventricular arrhythmias, LQTS,and SCD.

Published
2014
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36. A Large Candidate Gene Survey Identifies the KCNE1D85N Polymorphism as a Possible Modulator of Drug-Induced Torsades de Pointes

Author

Kääb, Stefan, Crawford, Dana C., Sinner, Moritz F., Behr, Elijah R., Kannankeril, Prince J., Wilde, Arthur A.M., Bezzina, Connie R., Schulze-Bahr, Eric, Guicheney, Pascale, Bishopric, Nanette H., Myerburg, Robert J., Schott, Jean-Jacques, Pfeufer, Arne, Beckmann, Britt-Maria, Martens, Eimo, Zhang, Taifang, Stallmeyer, Birgit, Zumhagen, Sven, Denjoy, Isabelle, Bardai, Abdennasser, Gelder, Isabelle C. Van, Jamshidi, Yalda, Dalageorgou, Chrysoula, Marshall, Vanessa, Jeffery, Steve, Shakir, Saad, Camm, A. John, Steinbeck, Gerhard, Perz, Siegfried, Lichtner, Peter, Meitinger, Thomas, Peters, Annette, Wichmann, H.-Erich, Ingram, Christiana, Bradford, Yuki, Carter, Shannon, Norris, Kris, Ritchie, Marylyn D., George, Alfred L., and Roden, Dan M.

Abstract

Drug-induced long-QT syndrome (diLQTS) is an adverse drug effect that has an important impact on drug use, development, and regulation. We tested the hypothesis that common variants in key genes controlling cardiac electric properties modify the risk of diLQTS.

Published
2012
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37. A Complex Double Deletion in LMNAUnderlies Progressive Cardiac Conduction Disease, Atrial Arrhythmias, and Sudden Death

Author

Marsman, Roos F., Bardai, Abdennasser, Postma, Alex V., Res, Jan C.J., Koopmann, Tamara T., Beekman, Leander, Wal, Allard C. van der, Pinto, Yigal M., Deprez, Ronald H. Lekanne, Wilde, Arthur A.M., Jordaens, Luc J., and Bezzina, Connie R.

Abstract

Cardiac conduction disease is a clinically and genetically heterogeneous disorder characterized by defects in electrical impulse generation and conduction and is associated with sudden cardiac death.

Published
2011
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38. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author

Yuki Bradford, Toshiko Tanaka, Jeffrey R. O'Connell, Florence Kyndt, Unnur Thorsteinsdottir, Ivana Kolcic, Xiaoyan Yin, Vincent Probst, Manolis Kellis, Christopher Newton-Cheh, Stefan Kääb, Argelia Medeiros-Domingo, Markus M. Nöthen, Paolo Gasparini, Jean-Jacques Schott, Ruth J. F. Loos, Thomas W. Mühleisen, Annukka Marjamaa, Morris Brown, Igor Rudan, Runjun D. Kumar, Peter J. Schwartz, Lars Lind, Martina Müller-Nurasyid, Xinchen Wang, Joshua C. Denny, Roberto Insolia, Soumya Raychaudhuri, Stephen W. Scherer, Bruno H. Stricker, Alexander Kluttig, Adamo Pio D'Adamo, Laurie A. Boyer, Moritz F. Sinner, Norbert Frey, Nour Eddine El Mokhtari, Thomas Meitinger, Jesper V. Olsen, Gerjan Navis, Steven R. Cummings, Richard W Morris, Nynke Hofman, Marcel den Hoed, Rudolf A. de Boer, Gonçalo R. Abecasis, Mark J. Daly, Dan M. Roden, Christian Gieger, Lyudmyla Kedenko, Marcus Dörr, Thomas P. Cappola, Afshin Parsa, Kari Stefansson, Markus Perola, Mark Eijgelsheim, Fredrik Nyberg, Robert M. Hamilton, Yalda Jamshidi, W. H. Linda Kao, Terho Lehtimäki, Annette Peters, David Schlessinger, Peter P. Pramstaller, James F. Wilson, Vilmundur Gudnason, Florian Kronenberg, Aroon D. Hingorani, Connie R. Bezzina, Abdennasser Bardai, Marylyn D. Ritchie, Andrew S. Plump, Johan Sundström, Daryl Waggott, Chrysoula Dalageorgou, Paul I.W. de Bakker, Uwe Völker, Aaron Isaacs, Oscar H. Franco, Yongmei Liu, Andrew N. Nicolaides, Lia Crotti, Cornelia M. van Duijn, Ben A. Oostra, Arne Pfeufer, Karl Werdan, Michael Morley, Jan A. Kors, Julien Barc, Lewin Eisele, Siegfried Perz, Stéphanie Chatel, Pieter A. van der Vleuten, Sara L. Pulit, Anna F. Dominiczak, Harry Campbell, Alice Ghidoni, Irene Mateo Leach, Nona Sotoodehnia, Nina Mononen, Henriette E. Meyer zu Schwabedissen, Alvaro Alonso, Fabiola Del Greco M, Dan E. Arking, Vera Adamkova, Mike A. Nalls, Valur Emilsson, Edward G. Lakatta, Kirill Tarasov, Alan F. Wright, Lenore J. Launer, Erik Ingelsson, Karin Halina Greiser, Ozren Polasek, Massimo Carella, Daniel F. Gudbjartsson, Bouwe P. Krijthe, Hanna Prucha, Per Hoffmann, Maura Griffin, Stefan Kiechl, Angel Carracedo, Ilja M. Nolte, Christine E. Moravec, Johann Willeit, Joshua C. Bis, Patricia B. Munroe, Marcello Ricardo Paulista Markus, Hailiang Huang, Mika Kähönen, Albert Hofman, Peter H. Whincup, Dirk J. van Veldhuisen, Michael Knoflach, Alicia Lundby, Serena Sanna, Hagen Kälsch, Bernhard Paulweber, Kamil Slowikowski, Luigi Ferrucci, Melanie Waldenberger, Marco Bobbo, Annukka M. Lahtinen, Ann-Christine Syvänen, J. Gustav Smith, Åsa Torinsson Naluai, Jaroslav A. Hubacek, Jeffrey Brandimarto, Wendy S. Post, Lude Franke, Mark J. Caulfield, Folkert W. Asselbergs, André G. Uitterlinden, Stefan Gustafsson, Pim van der Harst, David J. Tester, David S. Siscovick, David O. Arnar, Sarah H Wild, Elizabeth J. Rossin, Albert V. Smith, Bruce M. Psaty, Georg Ehret, Alan R. Shuldiner, Stephen Newhouse, Kimmo Kontula, Maria Brion, Andre Franke, Peter W. Macfarlane, Mika Kivimäki, Tamara B. Harris, Lasse Oikarinen, Tamara T. Koopmann, Kenneth B. Margulies, Aravinda Chakravarti, Gianfranco Sinagra, Maarten P. van den Berg, Veikko Salomaa, Karl-Heinz Jöckel, Daniel S. Evans, Caroline Hayward, Kimmo Porthan, Michael J. Ackerman, Jacqueline C.M. Witteman, Arthur A.M. Wilde, Martin G. Larson, Kasper Lage, Manuela Uda, Susan R. Heckbert, Joel S. Bader, Graham Watt, María Dolores Torres, Stephan B. Felix, Jerome I. Rotter, Pau Navarro, Meena Kumari, Johan Ärnlöv, Andrew D. Paterson, Antti Jula, Olli T. Raitakari, Raimund Erbel, Christopher J. O'Donnell, Britt M. Beckmann, Peter A. Noseworthy, Tim D. Spector, Wai K. Lee, Leopoldo Zelante, Nilesh J. Samani, John R. Giudicessi, Harold Snieder, Dag S. Thelle, David Ellinghaus, Eimo Martens, James B. Strait, Jorma S. A. Viikari, Andrew D. Johnson, Antonella Mulas, Hilma Holm, Johannes Haerting, Annamaria Iorio, Rebecca L. Zuvich, Sheila Ulivi, Andrew A. Hicks, Elijah R. Behr, Leo-Pekka Lyytikäinen, Bernhard Strohmer, Marco Orru, Claudia Lamina, Sandosh Padmanabhan, Christian Fuchsberger, Andrie G. Panayiotou, Ehret, Georg Benedikt, Internal Medicine, Public Health, Epidemiology, Rehabilitation Medicine, Medical Informatics, Clinical Genetics, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Ethical, Legal, Social Issues in Genetics (ELSI), Stem Cell Aging Leukemia and Lymphoma (SALL), Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, Dan E., Pulit, Sara L., Crotti, Lia, Van Der Harst, Pim, Munroe, Patricia B., Koopmann, Tamara T., Sotoodehnia, Nona, Rossin, Elizabeth J., Morley, Michael, Wang, Xinchen, Johnson, Andrew D., Lundby, Alicia, Gudbjartsson, Daníel F., Noseworthy, Peter A., Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V., Dörr, Marcu, Müller Nurasyid, Martina, Lahtinen, Annukka M., Nolte, Ilja M., Smith, Albert Vernon, Bis, Joshua C., Isaacs, Aaron, Newhouse, Stephen J., Evans, Daniel S., Post, Wendy S., Waggott, Daryl, Lyytikäinen, Leo Pekka, Hicks, Andrew A., Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J., Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W., Naluai, Asa T., Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G., Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A., Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D., Harris, Tamara B., Launer, Lenore J., Shuldiner, Alan R., Alonso, Alvaro, Bader, Joel S., Ehret, Georg, Huang, Hailiang, Kao, W. H. Linda, Strait, James B., Macfarlane, Peter W., Brown, Morri, Caulfield, Mark J., Samani, Nilesh J., Kronenberg, Florian, Willeit, Johann, Smith, J. Gustav, Greiser, Karin H., Zu Schwabedissen, Henriette Meyer, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R., Psaty, Bruce M., Rotter, Jerome I., Kolcic, Ivana, Polašek, Ozren, Wright, Alan F., Griffin, Maura, Daly, Mark J., Arnar, David O., Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C., Roden, Dan M., Zuvich, Rebecca L., Emilsson, Valur, Plump, Andrew S., Larson, Martin G., O'Donnell, Christopher J., Yin, Xiaoyan, Bobbo, Marco, D'Adamo, ADAMO PIO, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R., Nalls, Michael A., Jula, Antti, Kontula, Kimmo K., Marjamaa, Annukka, Oikarinen, Lasse, Perola, Marku, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl Heinz, Kälsch, Hagen, Nöthen, Markus M., Den Hoed, Marcel, Loos, Ruth J. F., Thelle, Dag S., Gieger, Christian, Meitinger, Thoma, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F., Waldenberger, Melanie, De Boer, Rudolf A., Franke, Lude, Van Der Vleuten, Pieter A., Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A. M., Behr, Elijah R., Dalageorgou, Chrysoula, Giudicessi, John R., Medeiros Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M., Scherer, Stephen W., Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E., Del Greco M, Fabiola, Fuchsberger, Christian, O'Connell, Jeffrey R., Lee, Wai K., Watt, Graham C. M., Campbell, Harry, Wild, Sarah H., El Mokhtari, Nour E., Frey, Norbert, Asselbergs, Folkert W., Leach, Irene Mateo, Navis, Gerjan, Van Den Berg, Maarten P., Van Veldhuisen, Dirk J., Kellis, Manoli, Krijthe, Bouwe P., Franco, Oscar H., Hofman, Albert, Kors, Jan A., Uitterlinden, André G., Witteman, Jacqueline C. M., Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A., Abecasis, Gonçalo R., Lakatta, Edward G., Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R. P., Völker, Uwe, Snieder, Harold, Spector, Timothy D., Ärnlöv, Johan, Lind, Lar, Sundström, Johan, Syvänen, Ann Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T., Viikari, Jorma S., Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N., Paulweber, Bernhard, Haerting, Johanne, Dominiczak, Anna F., Nyberg, Fredrik, Whincup, Peter H., Hingorani, Aroon D., Schott, Jean Jacque, Bezzina, Connie R., Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F., Rudan, Igor, Franke, Andre, Mühleisen, Thomas W., Pramstaller, Peter P., Lehtimäki, Terho J., Paterson, Andrew D., Parsa, Afshin, Liu, Yongmei, Van Duijn, Cornelia M., Siscovick, David S., Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B., Sanna, Serena, Ritchie, Marylyn D., Stricker, Bruno H., Stefansson, Kari, Boyer, Laurie A., Cappola, Thomas P., Olsen, Jesper V., Lage, Kasper, Schwartz, Peter J., Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J., Pfeufer, Arne, De Bakker, Paul I. W., Newton Cheh, Christopher, Cardiology, ACS - Amsterdam Cardiovascular Sciences, and Human Genetics

Subjects
Male, Candidate gene, Myocardium/metabolism, LOCI, Medizin, Heart electrophysiology, Genome-wide association study, Arrhythmias, Bioinformatics, Medical and Health Sciences, Heart Ventricle, Sudden cardiac death, Electrocardiography, PR INTERVAL, Arrhythmias, Cardiac/genetics, Death, Sudden, Cardiac/etiology, Genetics, ddc:616, Cardiac electrophysiology, Adult, Aged, Arrhythmias, Cardiac, Calcium Signaling, Death, Sudden, Cardiac, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Heart Ventricles, Humans, Long QT Syndrome, Middle Aged, Myocardium, Polymorphism, Single Nucleotide, COMMON VARIANTS, Heart Ventricles/metabolism, Single Nucleotide, Long QT Syndrome/genetics, CHRONIC HEART-FAILURE, Death, Heart ventricle arrhythmia, genetic association study, gene, SNP, heart, Genome-Wide Association Study/methods, Long QT syndrome, QRS DURATION, Cardiac, Cardiac/etiology, Human, QT interval, congenital, hereditary, and neonatal diseases and abnormalities, Electrocardiography/methods, TRPM7, BIO/18 - GENETICA, Cardiac/genetics, Biology, Article, sudden cardiac death, QRS complex, CARDIAC REPOLARIZATION, medicine, Repolarization, cardiovascular diseases, GENOME-WIDE ASSOCIATION, Polymorphism, MED/01 - STATISTICA MEDICA, calcium, ta1184, Calcium signaling, Calcium Signaling/genetics, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, ta3121, Cardiovascular risk, medicine.disease, SARCOPLASMIC-RETICULUM, Sudden, MODEL, Genetic association, myocardial repolarization, Genetic variability, Gene expression, Clinical Medicine, genetic, Controlled study
Abstract

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain similar to 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Published
2014

39. Sudden cardiac arrest in people with epilepsy in the community: Circumstances and risk factors.

Author

Lamberts RJ, Blom MT, Wassenaar M, Bardai A, Leijten FS, de Haan GJ, Sander JW, Thijs RD, and Tan HL

Subjects
Adult, Aged, Aged, 80 and over, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Case-Control Studies, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Prospective Studies, Registries, Risk Factors, Young Adult, Death, Sudden, Cardiac epidemiology, Epilepsy diagnosis, Epilepsy epidemiology, Residence Characteristics
Abstract

Objective: To ascertain whether characteristics of ventricular tachycardia/fibrillation (VT/VF) differed between people with epilepsy and those without and which individuals with epilepsy were at highest risk., Methods: We ascertained 18 people with active epilepsy identified in a community-based registry of sudden cardiac arrest (SCA) with ECG-confirmed VT/VF (cases). We compared them with 470 individuals with VT/VF without epilepsy (VT/VF controls) and 54 individuals with epilepsy without VT/VF (epilepsy controls). Data on comorbidity, epilepsy severity, and medication use were collected and entered into (conditional) logistic regression models to identify determinants of VT/VF in epilepsy., Results: In most cases, there was an obvious (10/18) or presumed cardiovascular cause (5/18) in view of preexisting heart disease. In 2 of the 3 remaining events, near-sudden unexpected death in epilepsy (SUDEP) was established after successful resuscitation. Cases had a higher prevalence of congenital/inherited heart disease (17% vs 1%, p = 0.002), and experienced VT/VF at younger age (57 vs 64 years, p = 0.023) than VT/VF controls. VT/VF in cases occurred more frequently at/near home (89% vs 58%, p = 0.009), and was less frequently witnessed (72% vs 89%, p = 0.048) than in VT/VF controls. Cases more frequently had clinically relevant heart disease (50% vs 15%, p = 0.005) and intellectual disability (28% vs 1%, p < 0.001) than epilepsy controls., Conclusion: Cardiovascular disease rather than epilepsy characteristics is the main determinant of VT/VF in people with epilepsy in the community. SCA and SUDEP are partially overlapping disease entities., (© 2015 American Academy of Neurology.)

Published
2015
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40. Reduced pre-hospital and in-hospital survival rates after out-of-hospital cardiac arrest of patients with type-2 diabetes mellitus: an observational prospective community-based study.

Author

Van Hoeijen DA, Blom MT, Bardai A, Souverein PC, De Boer A, and Tan HL

Subjects
Aged, Aged, 80 and over, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 physiopathology, Electrocardiography, Female, Humans, Hypoglycemic Agents therapeutic use, Male, Middle Aged, Nervous System physiopathology, Out-of-Hospital Cardiac Arrest diagnosis, Out-of-Hospital Cardiac Arrest physiopathology, Out-of-Hospital Cardiac Arrest therapy, Patient Discharge, Predictive Value of Tests, Prognosis, Prospective Studies, Registries, Risk Factors, Severity of Illness Index, Survival Rate, Tachycardia, Ventricular diagnosis, Tachycardia, Ventricular physiopathology, Tachycardia, Ventricular therapy, Ventricular Fibrillation diagnosis, Ventricular Fibrillation physiopathology, Ventricular Fibrillation therapy, Diabetes Mellitus, Type 2 mortality, Emergency Medical Services, Hospital Mortality, Out-of-Hospital Cardiac Arrest mortality, Tachycardia, Ventricular mortality, Ventricular Fibrillation mortality
Abstract

Aims: Out-of-hospital cardiac arrest (OHCA) remains a major cause of death. We aimed to determine whether type-2 diabetes mellitus (T2DM) is associated with reduced pre-hospital and in-hospital survival rates after OHCA., Methods and Results: An observational community-based cohort study was performed among 1549 OHCA patients with ECG-documented ventricular tachycardia/ventricular fibrillation (VT/VF). We compared pre-hospital and in-hospital survival rates between T2DM patients and non-diabetic patients. Analyses among T2DM patients were stratified according to current T2DM treatment, used as proxy for T2DM severity. Proportions of neurologically intact survival were analysed. Pre-hospital survival rates were lower in T2DM patients (n = 275) than in non-diabetic patients (n = 1274); 48.7 vs. 55.8% (univariate P = 0.032). Type-2 diabetes mellitus was associated with lower pre-hospital survival [OR 0.75 (0.58-0.98); after evaluation of the risk factors, we found no relevant confounding]. Patients treated with insulin only had lower pre-hospital survival rates than patients treated with oral glucose-lowering drugs only (37.3 vs. 53.3%, univariate P = 0.034), partially explained by location of OHCA and EMS response time [ORadj 0.62 (0.33-1.17)]. In-hospital survival rates were also lower in T2DM patients (n = 134) than in non-diabetic patients (n = 711); 40.3 vs. 57.7%, univariate P < 0.001. In those patients whose cause of OHCA was retrieved (n = 771), T2DM was significantly associated with lower in-hospital survival [ORadj 0.57 (0.37-0.87)]. Neurologically intact status at discharge was similarly high among T2DM and non-diabetic patients (94.4 vs. 94.6%, P = 0.954)., Conclusion: T2DM is associated with lower pre-hospital and in-hospital survival rates after OHCA. Neurologically intact status at hospital discharge is high both among T2DM and non-diabetic patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Published
2015
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41. Giant T-U waves precede torsades de pointes in long QT syndrome: a systematic electrocardiographic analysis in patients with acquired and congenital QT prolongation.

Author

Kirchhof P, Franz MR, Bardai A, and Wilde AM

Subjects
Adult, Aged, Diagnosis, Differential, Female, Follow-Up Studies, Humans, Long QT Syndrome complications, Long QT Syndrome congenital, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Torsades de Pointes diagnosis, Torsades de Pointes etiology, Ventricular Premature Complexes diagnosis, Ventricular Premature Complexes physiopathology, Electrocardiography, Heart Rate physiology, Long QT Syndrome physiopathology, Torsades de Pointes physiopathology
Abstract

Objectives: This study sought to identify electrocardiographic (ECG) criteria that are associated with initiation of torsades de pointes (TdP) in patients with acquired (a-) and congenital (c-) long QT syndrome (LQTS)., Background: Electrocardiographic criteria used as risk predictors for TdP commonly rely on a prolonged QT interval but rarely consider abnormal T-U waves., Methods: We analyzed ECG recordings with TdP from 35 LQTS patients (15 c-LQTS and 20 a-LQTS) and compared them with premature ventricular complexes (PVCs) from 40 patients with normal QT intervals and with PVCs in 24 of the 35 LQTS patients not related to TdP., Results: Abnormal T-U waves (6.2 +/- 0.9 mm) directly preceded TdP in 34 of 35 LQTS patients and were larger than T-wave amplitude (2.8 +/- 0.2 mm) in control patients and larger than the largest T-U-wave in LQTS without TdP (4.7 +/- 0.8 mm). The TdP-initiating beat emerged from a T-U-wave in 27 of 35 LQTS patients and in none of 40 control patients. The QRS duration of the first TdP beat (175 +/- 12 ms) was longer than in control PVCs (145 +/- 4 ms) and in PVCs in LQTS patients not related to TdP (138 +/- 22 ms). The QRS angle was less steep before TdP than in other PVCs (all p < 0.05)., Conclusions: Abnormal, giant T-U waves separate TdP initiation in LQTS patients from PVCs in other heart disease and from other PVCs in LQTS patients. These ECG analyses suggest that early afterdepolarizations initiate TdP and, if present, may help to identify an imminent risk for TdP.

Published
2009
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