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454 results on '"Kääb, S"'

1. EYE-EKG2: Verbesserung der EKG-Befundungskompetenz von Medizinstudierenden durch Eyetracking und Cued Retrospective Reporting

Author: Scherff, AD, Kääb, S, Fischer, MR, Berndt, M, Scherff, AD, Kääb, S, Fischer, MR, and Berndt, M
Published: 2023

2. Genetic insights into resting heart rate and its role in cardiovascular disease.

Author: Vegte, Y.J. van de, Eppinga, R.N., Ende, M.Y. van der, Hagemeijer, Y.P., Mahendran, Y., Salfati, E., Smith, A.V., Tan, V.Y., Arking, D.E., Ntalla, I., Appel, E.V., Schurmann, C., Brody, J.A., Rueedi, R., Polasek, O., Sveinbjornsson, G., Lecoeur, C., Ladenvall, C., Zhao, J.H., Isaacs, A., Wang, L., Luan, Jian'an, Hwang, S.J., Mononen, N., Auro, K., Jackson, A.U., Bielak, L.F., Zeng, L., Shah, N., Nethander, M., Campbell, A., Rankinen, T., Pechlivanis, S., Qi, L., Zhao, Wei, Rizzi, F., Tanaka, T., Robino, A., Cocca, M., Lange, L., Müller-Nurasyid, M., Roselli, C., Zhang, W, Kleber, M.E., Guo, X., Lin, H.J., Pavani, F., Galesloot, T.E., Noordam, R., Milaneschi, Y., Schraut, K.E., Hoed, M. den, Degenhardt, F., Trompet, S., Berg, M.E. van den, Pistis, G., Tham, Y.C., Weiss, S., Sim, X.S., Li, H.L., Most, P.J. van der, Nolte, I.M., Lyytikäinen, L.P., Said, M.A., Witte, D.R., Iribarren, C., Launer, L., Ring, S.M., Vries, P.S. de, Sever, P., Linneberg, A., Bottinger, E.P., Padmanabhan, S., Psaty, B.M., Sotoodehnia, N., Kolcic, I., Arnar, D.O., Gudbjartsson, D.F., Holm, H., Balkau, B., Silva, C.T., Newton-Cheh, C.H., Nikus, K., Salo, P., Mohlke, K.L., Peyser, P.A., Schunkert, H., Lorentzon, M., Lahti, J., Rao, D.C., Cornelis, M.C., Faul, J.D., Smith, J.A., Stolarz-Skrzypek, K., Bandinelli, S., Concas, M.P., Sinagra, G., Meitinger, T., Waldenberger, M., Sinner, M.F., Strauch, K., Delgado, G.E., Taylor, K.D., Yao, J., Foco, L., Melander, O., Graaf, J. de, Mutsert, R. de, Geus, E.J.C. de, Johansson, Å., Joshi, P.K., Lind, L., Franke, A., Macfarlane, P.W., Tarasov, K.V., Tan, N., Felix, S.B., Tai, E.S., Quek, D.Q., Snieder, H., Ormel, J., Ingelsson, M., Lindgren, C., Morris, A.P., Raitakari, O.T., Hansen, T., Assimes, T., Gudnason, V., Timpson, N.J., Morrison, A.C., Munroe, P.B., Strachan, D.P., Grarup, N., Loos, R.J.F., Heckbert, S.R., Vollenweider, P., Hayward, C., Stefansson, K., Froguel, P., Groop, L., Wareham, N.J., Duijn, C.M. van, Feitosa, M.F., O'Donnell, C.J., Kähönen, M., Perola, M., Boehnke, M., Kardia, S.L.R., Erdmann, J., Palmer, C.N.A., Ohlsson, C., Porteous, D.J., Eriksson, J.G., Bouchard, C., Moebus, S., Kraft, P., Weir, D.R., Cusi, D., Ferrucci, L., Ulivi, S., Girotto, G., Correa, A., Kääb, S., Peters, A., Chambers, J.C., Kooner, J.S., März, W., Rotter, J.I., Hicks, A.A., Smith, J.G., Kiemeney, L.A.L.M., Mook-Kanamori, D.O., Penninx, B.W.J.H., Gyllensten, U., Wilson, J.F., Burgess, S., Sundström, J., Lieb, W., Jukema, J.W., Eijgelsheim, M., Lakatta, E.L.M., Cheng, C.Y., Dörr, M., Wong, T.Y., Sabanayagam, C., Oldehinkel, A.J., Riese, H., Lehtimäki, T., Verweij, N., Harst, P. van der, Vegte, Y.J. van de, Eppinga, R.N., Ende, M.Y. van der, Hagemeijer, Y.P., Mahendran, Y., Salfati, E., Smith, A.V., Tan, V.Y., Arking, D.E., Ntalla, I., Appel, E.V., Schurmann, C., Brody, J.A., Rueedi, R., Polasek, O., Sveinbjornsson, G., Lecoeur, C., Ladenvall, C., Zhao, J.H., Isaacs, A., Wang, L., Luan, Jian'an, Hwang, S.J., Mononen, N., Auro, K., Jackson, A.U., Bielak, L.F., Zeng, L., Shah, N., Nethander, M., Campbell, A., Rankinen, T., Pechlivanis, S., Qi, L., Zhao, Wei, Rizzi, F., Tanaka, T., Robino, A., Cocca, M., Lange, L., Müller-Nurasyid, M., Roselli, C., Zhang, W, Kleber, M.E., Guo, X., Lin, H.J., Pavani, F., Galesloot, T.E., Noordam, R., Milaneschi, Y., Schraut, K.E., Hoed, M. den, Degenhardt, F., Trompet, S., Berg, M.E. van den, Pistis, G., Tham, Y.C., Weiss, S., Sim, X.S., Li, H.L., Most, P.J. van der, Nolte, I.M., Lyytikäinen, L.P., Said, M.A., Witte, D.R., Iribarren, C., Launer, L., Ring, S.M., Vries, P.S. de, Sever, P., Linneberg, A., Bottinger, E.P., Padmanabhan, S., Psaty, B.M., Sotoodehnia, N., Kolcic, I., Arnar, D.O., Gudbjartsson, D.F., Holm, H., Balkau, B., Silva, C.T., Newton-Cheh, C.H., Nikus, K., Salo, P., Mohlke, K.L., Peyser, P.A., Schunkert, H., Lorentzon, M., Lahti, J., Rao, D.C., Cornelis, M.C., Faul, J.D., Smith, J.A., Stolarz-Skrzypek, K., Bandinelli, S., Concas, M.P., Sinagra, G., Meitinger, T., Waldenberger, M., Sinner, M.F., Strauch, K., Delgado, G.E., Taylor, K.D., Yao, J., Foco, L., Melander, O., Graaf, J. de, Mutsert, R. de, Geus, E.J.C. de, Johansson, Å., Joshi, P.K., Lind, L., Franke, A., Macfarlane, P.W., Tarasov, K.V., Tan, N., Felix, S.B., Tai, E.S., Quek, D.Q., Snieder, H., Ormel, J., Ingelsson, M., Lindgren, C., Morris, A.P., Raitakari, O.T., Hansen, T., Assimes, T., Gudnason, V., Timpson, N.J., Morrison, A.C., Munroe, P.B., Strachan, D.P., Grarup, N., Loos, R.J.F., Heckbert, S.R., Vollenweider, P., Hayward, C., Stefansson, K., Froguel, P., Groop, L., Wareham, N.J., Duijn, C.M. van, Feitosa, M.F., O'Donnell, C.J., Kähönen, M., Perola, M., Boehnke, M., Kardia, S.L.R., Erdmann, J., Palmer, C.N.A., Ohlsson, C., Porteous, D.J., Eriksson, J.G., Bouchard, C., Moebus, S., Kraft, P., Weir, D.R., Cusi, D., Ferrucci, L., Ulivi, S., Girotto, G., Correa, A., Kääb, S., Peters, A., Chambers, J.C., Kooner, J.S., März, W., Rotter, J.I., Hicks, A.A., Smith, J.G., Kiemeney, L.A.L.M., Mook-Kanamori, D.O., Penninx, B.W.J.H., Gyllensten, U., Wilson, J.F., Burgess, S., Sundström, J., Lieb, W., Jukema, J.W., Eijgelsheim, M., Lakatta, E.L.M., Cheng, C.Y., Dörr, M., Wong, T.Y., Sabanayagam, C., Oldehinkel, A.J., Riese, H., Lehtimäki, T., Verweij, N., and Harst, P. van der
Abstract: Contains fulltext : 296013.pdf (Publisher’s version ) (Open Access), Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
Published: 2023

3. High-density Mapping Guided Pulmonary Vein Isolation for Treatment of Atrial Fibrillation - Two-year clinical outcome of a single center experience

Author: Siebermair, J., Neumann, B., Risch, F., Riesinger, L., Vonderlin, N., Koehler, M., Lackermaier, K., Fichtner, S., Rizas, K., Sattler, S. M., Sinner, M. F., Kääb, S., Estner, H. L., and Wakili, R.
Published: 2019
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4. COGIA – Clinical course, outcome and genetics of inherited arrhythmias in children: a German multicenter study

Author: Lippert, L., additional, Burkard, T., additional, Markel, F., additional, Debus, V., additional, Stute, F., additional, Kamphues, A., additional, Dalla-Pozza, R., additional, Rupp, S., additional, Gonzalez y Gonzalez, M. B., additional, Junge, C., additional, Kanaan, M., additional, Hoff, K., additional, Hanser, A., additional, Dittmann, S., additional, Westphal, D. S., additional, Clauss, S., additional, Hitz, M. P., additional, Becker, K., additional, Kääb, S., additional, Ewert, P., additional, Hofbeck, M., additional, Wällisch, W., additional, Dittrich, S., additional, Uebing, A., additional, Nürnberg, J. H., additional, Hebe, J., additional, Kozlik-Feldmann, R., additional, Beerbaum, P., additional, Kerst, G., additional, Kehl, H. G., additional, Schulze-Bahr, E., additional, Gebauer, R., additional, Hessling, G., additional, and Wolf, C. M., additional
Published: 2023
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5. Safety and efficacy in ablation of premature ventricular contraction: data from the German ablation registry

Author: Fichtner, S., Senges, J., Hochadel, M., Tilz, R., Willems, S., Eckardt, L., Deneke, T., Lewalter, T., Dorwarth, U., Reithmann, C., Brachmann, J., Steinbeck, G., Kääb, S., and for the German Ablation Registry
Published: 2017
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6. Transethnic genome-wide association study provides insights in the genetic architecture and heritability of long QT syndrome

Author: Lahrouchi, N, Tadros, R, Crotti, L, Mizusawa, Y, Postema, P, Beekman, L, Walsh, R, Hasegawa, K, Barc, J, Ernsting, M, Turkowski, K, Mazzanti, A, Beckmann, B, Shimamoto, K, Diamant, U, Wijeyeratne, Y, Kucho, Y, Robyns, T, Ishikawa, T, Arbelo, E, Christiansen, M, Winbo, A, Jabbari, R, Lubitz, S, Steinfurt, J, Rudic, B, Loeys, B, Shoemaker, M, Weeke, P, Pfeiffer, R, Davies, B, Andorin, A, Hofman, N, Dagradi, F, Pedrazzini, M, Tester, D, Bos, J, Sarquella-Brugada, G, Campuzano, Ó, Platonov, P, Stallmeyer, B, Zumhagen, S, Nannenberg, E, Veldink, J, van den Berg, L, Al-Chalabi, A, Shaw, C, Shaw, P, Morrison, K, Andersen, P, Müller-Nurasyid, M, Cusi, D, Barlassina, C, Galan, P, Lathrop, M, Munter, M, Werge, T, Ribasés, M, Aung, T, Khor, C, Ozaki, M, Lichtner, P, Meitinger, T, van Tintelen, J, Hoedemaekers, Y, Denjoy, I, Leenhardt, A, Napolitano, C, Shimizu, W, Schott, J, Gourraud, J, Makiyama, T, Ohno, S, Itoh, H, Krahn, A, Antzelevitch, C, Roden, D, Saenen, J, Borggrefe, M, Odening, K, Ellinor, P, Tfelt-Hansen, J, Skinner, J, van den Berg, M, Olesen, M, Brugada, J, Brugada, R, Makita, N, Breckpot, J, Yoshinaga, M, Behr, E, Rydberg, A, Aiba, T, Kääb, S, Priori, S, Guicheney, P, Tan, H, Newton-Cheh, C, Ackerman, M, Schwartz, P, Schulze-Bahr, E, Probst, V, Horie, M, Wilde, A, Tanck, M, Bezzina, C, Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, Postema PG, Beekman L, Walsh R, Hasegawa K, Barc J, Ernsting M, Turkowski KL, Mazzanti A, Beckmann BM, Shimamoto K, Diamant UB, Wijeyeratne YD, Kucho Y, Robyns T, Ishikawa T, Arbelo E, Christiansen M, Winbo A, Jabbari R, Lubitz SA, Steinfurt J, Rudic B, Loeys B, Shoemaker MB, Weeke PE, Pfeiffer R, Davies B, Andorin A, Hofman N, Dagradi F, Pedrazzini M, Tester DJ, Bos JM, Sarquella-Brugada G, Campuzano Ó, Platonov PG, Stallmeyer B, Zumhagen S, Nannenberg EA, Veldink JH, van den Berg LH, Al-Chalabi A, Shaw CE, Shaw PJ, Morrison KE, Andersen PM, Müller-Nurasyid M, Cusi D, Barlassina C, Galan P, Lathrop M, Munter M, Werge T, Ribasés M, Aung T, Khor CC, Ozaki M, Lichtner P, Meitinger T, van Tintelen JP, Hoedemaekers Y, Denjoy I, Leenhardt A, Napolitano C, Shimizu W, Schott JJ, Gourraud JB, Makiyama T, Ohno S, Itoh H, Krahn AD, Antzelevitch C, Roden DM, Saenen J, Borggrefe M, Odening KE, Ellinor PT, Tfelt-Hansen J, Skinner JR, van den Berg MP, Olesen MS, Brugada J, Brugada R, Makita N, Breckpot J, Yoshinaga M, Behr ER, Rydberg A, Aiba T, Kääb S, Priori SG, Guicheney P, Tan HL, Newton-Cheh C, Ackerman MJ, Schwartz PJ, Schulze-Bahr E, Probst V, Horie M, Wilde AA, Tanck MWT, Bezzina CR., Lahrouchi, N, Tadros, R, Crotti, L, Mizusawa, Y, Postema, P, Beekman, L, Walsh, R, Hasegawa, K, Barc, J, Ernsting, M, Turkowski, K, Mazzanti, A, Beckmann, B, Shimamoto, K, Diamant, U, Wijeyeratne, Y, Kucho, Y, Robyns, T, Ishikawa, T, Arbelo, E, Christiansen, M, Winbo, A, Jabbari, R, Lubitz, S, Steinfurt, J, Rudic, B, Loeys, B, Shoemaker, M, Weeke, P, Pfeiffer, R, Davies, B, Andorin, A, Hofman, N, Dagradi, F, Pedrazzini, M, Tester, D, Bos, J, Sarquella-Brugada, G, Campuzano, Ó, Platonov, P, Stallmeyer, B, Zumhagen, S, Nannenberg, E, Veldink, J, van den Berg, L, Al-Chalabi, A, Shaw, C, Shaw, P, Morrison, K, Andersen, P, Müller-Nurasyid, M, Cusi, D, Barlassina, C, Galan, P, Lathrop, M, Munter, M, Werge, T, Ribasés, M, Aung, T, Khor, C, Ozaki, M, Lichtner, P, Meitinger, T, van Tintelen, J, Hoedemaekers, Y, Denjoy, I, Leenhardt, A, Napolitano, C, Shimizu, W, Schott, J, Gourraud, J, Makiyama, T, Ohno, S, Itoh, H, Krahn, A, Antzelevitch, C, Roden, D, Saenen, J, Borggrefe, M, Odening, K, Ellinor, P, Tfelt-Hansen, J, Skinner, J, van den Berg, M, Olesen, M, Brugada, J, Brugada, R, Makita, N, Breckpot, J, Yoshinaga, M, Behr, E, Rydberg, A, Aiba, T, Kääb, S, Priori, S, Guicheney, P, Tan, H, Newton-Cheh, C, Ackerman, M, Schwartz, P, Schulze-Bahr, E, Probst, V, Horie, M, Wilde, A, Tanck, M, Bezzina, C, Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, Postema PG, Beekman L, Walsh R, Hasegawa K, Barc J, Ernsting M, Turkowski KL, Mazzanti A, Beckmann BM, Shimamoto K, Diamant UB, Wijeyeratne YD, Kucho Y, Robyns T, Ishikawa T, Arbelo E, Christiansen M, Winbo A, Jabbari R, Lubitz SA, Steinfurt J, Rudic B, Loeys B, Shoemaker MB, Weeke PE, Pfeiffer R, Davies B, Andorin A, Hofman N, Dagradi F, Pedrazzini M, Tester DJ, Bos JM, Sarquella-Brugada G, Campuzano Ó, Platonov PG, Stallmeyer B, Zumhagen S, Nannenberg EA, Veldink JH, van den Berg LH, Al-Chalabi A, Shaw CE, Shaw PJ, Morrison KE, Andersen PM, Müller-Nurasyid M, Cusi D, Barlassina C, Galan P, Lathrop M, Munter M, Werge T, Ribasés M, Aung T, Khor CC, Ozaki M, Lichtner P, Meitinger T, van Tintelen JP, Hoedemaekers Y, Denjoy I, Leenhardt A, Napolitano C, Shimizu W, Schott JJ, Gourraud JB, Makiyama T, Ohno S, Itoh H, Krahn AD, Antzelevitch C, Roden DM, Saenen J, Borggrefe M, Odening KE, Ellinor PT, Tfelt-Hansen J, Skinner JR, van den Berg MP, Olesen MS, Brugada J, Brugada R, Makita N, Breckpot J, Yoshinaga M, Behr ER, Rydberg A, Aiba T, Kääb S, Priori SG, Guicheney P, Tan HL, Newton-Cheh C, Ackerman MJ, Schwartz PJ, Schulze-Bahr E, Probst V, Horie M, Wilde AA, Tanck MWT, and Bezzina CR.
Abstract: Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P5×10-8) near NOS1AP, KCNQ1, and KLF12, and 1 missense variant in KCNE1(p.Asp85Asn) at the suggestive threshold (P10-6). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (rg=0.40; P=3.2×10-3). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS c
Published: 2020

7. Effects of expert eye-tracking videos with cued retrospective reporting on medical students' ECG interpretation skills

Author: Scherff, AD, Kääb, S, Fischer, MR, Berndt, M, Scherff, AD, Kääb, S, Fischer, MR, and Berndt, M
Published: 2022

8. 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

9. 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

10. Remote monitoring of implantable cardioverter-defibrillators: Problems and implications using a telemonitoring system

Author: Siebermair, J., Clauss, S., Martens, E., Schuessler, F., Oversohl, N., Haserueck, N., Estner, H.L., Kääb, S., and Wakili, R.
Published: 2015
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11. EYE-ECG: An RCT of the influence of student characteristics and expert eye-tracking videos with cued retrospective reporting on students’ ECG interpretation skills

Author: Scherff, Aline D., Kääb, Stefan, Fischer, Martin R., and Berndt, Markus
Subjects: eye-tracking, learning, electrocardiography, students, medical, clinical reasoning, diagnosis, Special aspects of education, LC8-6691, Medicine
Abstract: Objectives: Teaching of ECG interpretation frequently relies on visual schemas. However, subsequent student ECG interpretation skills are often poor. Expertise research shows that expert looking patterns frequently deviate from the steps taught in schema learning. The present study made a cardiology expert’s gaze interpreting ECGs visible – through eye-tracking videos with cued retrospective reporting (CRR) – and investigated the potential as an additional expert-driven route to improve medical students’ ECG interpretation skills.Methods: =91 Medical students participated in the RCT of an ECG e-learning session aimed at medical students’ ECG interpretation skills gain, either receiving the newly developed eye-tracking video with CRR audio commentary materials (=47) or studying via four clinical cases only (=44). Three outcome scores relating to different aspects of ECG interpretation skills were derived from pre-post MCQ ECG tests. The effect of the EYE-ECG training and additional characteristics (e.g., prior experience, interest) on student ECG interpretation skills were evaluated using t-tests and multivariate linear regression.Results: A small, non-significant advantage of the EYE-ECG training signifying a tendency for greater knowledge gain was observed, compared to training as usual. In multivariate regression models, the predictive value of clinical case 1 was an unexpected finding warranting further exploration.Conclusion: Additional gains after an only 9-minute intervention using videos of expert’s real-time gaze pattern in combination with hearing their thought processes during ECG interpretation is a promising finding. Furthermore, a number of specific performance characteristics enabling students to best benefit from ECG training were identified and possible modifications to the learning intervention suggested.
Published: 2024
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12. MRT-Bildgebung bei hypertropher Kardiomyopathie (HCM): Evaluation der diastolischen Funktion

Author: Schwarz, F., Schwab, F., Beckmann, B.M., Schuessler, F., Zinsser, D., Gölz, T., Kääb, S., Reiser, M.F., and Theisen, D.
Published: 2013
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13. 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 PG, Amin AS, Nannenberg EA, Ware JS, Whiffin N, Mazzarotto F, Škoric-Milosavljevic D, Krijger C, Arbelo E, Babuty D, Barajas-Martinez H, Beckmann BM, Bézieau S, Bos JM, Breckpot J, Campuzano O, Castelletti S, Celen C, Clauss S, Corveleyn A, Crotti L, Dagradi F, de Asmundis C, Denjoy I, Dittmann S, Ellinor PT, Ortuño CG, Giustetto C, Gourraud JB, Hazeki D, Horie M, Ishikawa T, Itoh H, Kaneko Y, Kanters JK, Kimoto H, Kotta MC, Krapels IPC, Kurabayashi M, Lazarte J, Leenhardt A, Loeys BL, Lundin C, Makiyama T, Mansourati J, Martins RP, Mazzanti A, Mörner S, Napolitano C, Ohkubo K, Papadakis M, Rudic B, Molina MS, Sacher F, Sahin H, Sarquella-Brugada G, Sebastiano R, Sharma S, Sheppard MN, Shimamoto K, Shoemaker MB, Stallmeyer B, Steinfurt J, Tanaka Y, Tester DJ, Usuda K, van der Zwaag PA, Van Dooren S, Van Laer L, Winbo A, Winkel BG, Yamagata K, Zumhagen S, Volders PGA, Lubitz SA, Antzelevitch C, Platonov PG, Odening KE, Roden DM, Roberts JD, Skinner JR, Tfelt-Hansen J, van den Berg MP, Olesen MS, Lambiase PD, Borggrefe M, Hayashi K, Rydberg A, Nakajima T, Yoshinaga M, Saenen JB, Kääb S, Brugada P, Robyns T, Giachino DF, Ackerman MJ, Brugada R, Brugada-Terradellas J, Gimeno JR, Hasdemir C, Guicheney P, Priori SG, Schulze-Bahr E, Makita N, Schwartz PJ, Shimizu W, Aiba T, Schott JJ, Redon R, Ohno S, Probst V, Behr ER, Barc J, Bezzina CR, and Nantes Referral Center for inherited cardiac arrhythmia
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, LQTS, variant interpretation, cardiovascular diseases, Brugada, ACMG/AMP guidelines
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

14. Nocturnal respiratory rate predicts ICD benefit:a prospective, controlled, multicentre cohort study

Author: Dommasch, M. (Michael), Steger, A. (Alexander), Barthel, P. (Petra), Huster, K. M. (Katharina M.), Müller, A. (Alexander), Sinnecker, D. (Daniel), Laugwitz, K.-L. (Karl-Ludwig), Penzel, T. (Thomas), Lubinski, A. (Andrzej), Flevari, P. (Panagiota), Harden, M. (Markus), Friede, T. (Tim), Kääb, S. (Stefan), Merkely, B. (Bela), Sticherling, C. (Christian), Willems, R. (Rik), Huikuri, H. V. (Heikki V.), Bauer, A. (Axel), Malik, M. (Marek), Zabel, M. (Markus), Schmidt, G. (Georg), and T. E. (The EU-CERT-ICD investigators)
Subjects: Benefit prediction, Nocturnal respiratory rate, Primary prophylactic ICD
Abstract: Background: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. ICD implantation decisions are currently based on reduced left ventricular ejection fraction (LVEF≤35%). However, in some patients, the non-arrhythmic death risk predominates thus diminishing ICD-therapy benefits. Based on previous observations, we tested the hypothesis that compared to the others, patients with nocturnal respiratory rate (NRR) ≥18 breaths per minute (brpm) benefit less from prophylactic ICD implantations. Methods: This prospective cohort study was a pre-defined sub-study of EU-CERT-ICD trial conducted at 44 centers in 15 EU countries between May 12, 2014, and September 6, 2018. Patients with ischaemic or non-ischaemic cardiomyopathy were included if meeting primary prophylactic ICD implantation criteria. The primary endpoint was all-cause mortality. NRR was assessed blindly from pre-implantation 24-hour Holters. Multivariable models and propensity stratification evaluated the interaction between NRR and the ICD mortality effect. This study is registered with ClinicalTrials.gov (NCT0206419). Findings: Of the 2,247 EU-CERT-ICD patients, this sub-study included 1,971 with complete records. In 1,363 patients (61.7 (12) years; 244 women) an ICD was implanted; 608 patients (63.2 (12) years; 108 women) were treated conservatively. During a median 2.5-year follow-up, 202 (14.8%) and 95 (15.6%) patients died in the ICD and control groups, respectively. NRR statistically significantly interacted with the ICD mortality effect (p = 0.0070). While the 1,316 patients with NRR
Published: 2021

15. 2020 APHRS/HRS Expert Consensus Statement on the Investigation of Decedents with Sudden Unexplained Death and Patients with Sudden Cardiac Arrest, and of Their Families

Author: Stiles, MK, Wilde, AAM, Abrams, DJ, Ackerman, MJ, Albert, CM, Behr, ER, Chugh, SS, Cornel, MC, Gardner, K, Grad, JI, James, CA, Jimmy Juang, J-M, Kääb, S, Kaufman, ES, Krahn, AD, Lubitz, SA, MacLeod, H, Morillo, CA, Nademanee, K, Probst, V, Saarel, EV, Sacilotto, L, Semsarian, C, Sheppard, MN, Shimizu, W, Skinner, JR, Tfelt-Hansen, J, Wang, DW, and Document Reviewers
Abstract: This international multidisciplinary document intends to provide clinicians with evidence-based practical patient-centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.
Published: 2021

16. Molekulare Mechanismen von Vorhofflimmern: Potenzielle Rolle der microRNAs als neues therapeutisches Ziel und als möglicher Biomarker

Author: Wakili, R., Clauß, S., and Kääb, S.
Published: 2012
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17. 22-jähriger Sportler mit Sinusarrest und Pausen bis 7 Sekunden

Author: Siebermair, J., Pohl, T., Wakili, R., Schüssler, F., Lange, P., Martens, E., Beckmann, B.M., Sinner, M.F., Steinbigler, P., Steinbeck, G., and Kääb, S.
Published: 2012
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18. Multimorbidität und erfolgreiches Altern: Ein Blick auf die Bevölkerung im Rahmen der KORA-Age-Studie

Author: Peters, A., Döring, A., Ladwig, K.-H., Meisinger, C., Linkohr, B., Autenrieth, C., Baumeister, S.E., Behr, J., Bergner, A., Bickel, H., Bidlingmaier, M., Dias, A., Emeny, R.T., Fischer, B., Grill, E., Gorzelniak, L., Hänsch, H., Heidbreder, S., Heier, M., Horsch, A., Huber, D., Huber, R.M., Jörres, R.A., Kääb, S., Karrasch, S., Kirchberger, I., Klug, G., Kranz, B., Kuch, B., Lacruz, M.E., Lang, O., Mielck, A., Nowak, D., Perz, S., Schneider, A., Schulz, H., Müller, M., Seidl, H., Strobl, R., Thorand, B., Wende, R., Weidenhammer, W., Zimmermann, A.-K., Wichmann, H.-E., and Holle, R.
Published: 2011
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19. Mortality due to myocardial infarction in the Bavarian population during World Cup Soccer 2006

Author: Wilbert-Lampen, U., Nickel, T., Scheipl, F., Greven, S., Küchenhoff, H., Kääb, S., and Steinbeck, G.
Published: 2011
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20. Extracorporal life support (ECLS) in acute ischaemic cardiogenic shock

Author: Sattler, S., Khaladj, N., Zaruba, M.-M., Fischer, M., Hausleiter, J., Mehilli, J., Kääb, S., Hagl, C., Massberg, S., and Theiss, H. D.
Published: 2014
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21. 64-jähriger Patient mit Herzrasen und Zeichen einer Herzinsuffizienz

Author: Zaruba, M.M., Waggershauser, T., Weckbach, S., Gerbes, A., Mühling, O., and Kääb, S.
Published: 2009
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22. Genetik von Vorhofflimmern: seltene Mutationen, häufige Genvarianten und klinische Relevanz?

Author: Sinner, M. F., Pfeufer, A., and Kääb, S.
Published: 2006
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23. Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome .

Author: Lahrouchi, N., Tadros, R., Crotti, L., Mizusawa, Y., Postema, P.G., Beekman, L., Walsh, R., Hasegawa, K., Barc, J., Ernsting, M., Turkowski, K.L., Mazzanti, A., Beckmann, B.M., Shimamoto, K., Diamant, U.B., Wijeyeratne, Y.D., Kucho, Y., Robyns, T., Ishikawa, T., Arbelo, E., Christiansen, M., Winbo, A., Jabbari, R., Lubitz, S.A., Steinfurt, J., Rudic, B., Loeys, B., Shoemaker, M.B., Weeke, P.E., Pfeiffer, R., Davies, B., Andorin, A., Hofman, N., Dagradi, F., Pedrazzini, M., Tester, D.J., Bos, J.M, Sarquella-Brugada, G., Campuzano, Ó., Platonov, P.G., Stallmeyer, B., Zumhagen, S., Nannenberg, E.A., Veldink, J.H., Berg, L.H. van den, Al-Chalabi, A., Shaw, C.E., Shaw, P.J., Morrison, K.E., Andersen, P.M., Müller-Nurasyid, M., Cusi, D., Barlassina, C., Galan, P., Lathrop, M., Munter, M., Werge, T., Ribasés, M., Aung, T., Khor, C.C., Ozaki, M., Lichtner, P., Meitinger, T., Tintelen, J.P. van, Hoedemaekers, Y.M., Denjoy, I., Leenhardt, A., Napolitano, C., Shimizu, W., Schott, J.J., Gourraud, J.B., Makiyama, T., Ohno, S., Itoh, H., Krahn, A.D., Antzelevitch, C., Roden, D.M., Saenen, J., Borggrefe, M., Odening, K.E., Ellinor, P.T., Tfelt-Hansen, J., Skinner, J.R., Berg, M.P., Olesen, M.S., Brugada, J., Brugada, R., Makita, N., Breckpot, J., Yoshinaga, M., Behr, E.R., Rydberg, A., Aiba, T., Kääb, S., Priori, S.G., Guicheney, P., Tan, H.L., Newton-Cheh, C., Ackerman, M.J., Schwartz, P.J., Lahrouchi, N., Tadros, R., Crotti, L., Mizusawa, Y., Postema, P.G., Beekman, L., Walsh, R., Hasegawa, K., Barc, J., Ernsting, M., Turkowski, K.L., Mazzanti, A., Beckmann, B.M., Shimamoto, K., Diamant, U.B., Wijeyeratne, Y.D., Kucho, Y., Robyns, T., Ishikawa, T., Arbelo, E., Christiansen, M., Winbo, A., Jabbari, R., Lubitz, S.A., Steinfurt, J., Rudic, B., Loeys, B., Shoemaker, M.B., Weeke, P.E., Pfeiffer, R., Davies, B., Andorin, A., Hofman, N., Dagradi, F., Pedrazzini, M., Tester, D.J., Bos, J.M, Sarquella-Brugada, G., Campuzano, Ó., Platonov, P.G., Stallmeyer, B., Zumhagen, S., Nannenberg, E.A., Veldink, J.H., Berg, L.H. van den, Al-Chalabi, A., Shaw, C.E., Shaw, P.J., Morrison, K.E., Andersen, P.M., Müller-Nurasyid, M., Cusi, D., Barlassina, C., Galan, P., Lathrop, M., Munter, M., Werge, T., Ribasés, M., Aung, T., Khor, C.C., Ozaki, M., Lichtner, P., Meitinger, T., Tintelen, J.P. van, Hoedemaekers, Y.M., Denjoy, I., Leenhardt, A., Napolitano, C., Shimizu, W., Schott, J.J., Gourraud, J.B., Makiyama, T., Ohno, S., Itoh, H., Krahn, A.D., Antzelevitch, C., Roden, D.M., Saenen, J., Borggrefe, M., Odening, K.E., Ellinor, P.T., Tfelt-Hansen, J., Skinner, J.R., Berg, M.P., Olesen, M.S., Brugada, J., Brugada, R., Makita, N., Breckpot, J., Yoshinaga, M., Behr, E.R., Rydberg, A., Aiba, T., Kääb, S., Priori, S.G., Guicheney, P., Tan, H.L., Newton-Cheh, C., Ackerman, M.J., and Schwartz, P.J.
Abstract: Contains fulltext : 230155.pdf (Publisher’s version ) (Open Access)
Published: 2020

24. The influence of prompts on final year medical students' learning process and achievement in ECG interpretation

Author: Berndt, M, Thomas, F, Bauer, D, Härtl, A, Hege, I, Kääb, S, Fischer, MR, Heitzmann, N, Berndt, M, Thomas, F, Bauer, D, Härtl, A, Hege, I, Kääb, S, Fischer, MR, and Heitzmann, N
Abstract: Objective: ECG interpretation is prone to errors that can lead to relevant misdiagnoses and incorrect treatment. Prompts are one way in lectures to encourage learning from one's own mistakes and to reduce error rates. Prompts are measures such as questions, hints, and suggestions of content-related or metacognitive nature, which can lead to self-explanation in the learner and thus to a deeper understanding of an issue. The aim of the study was therefore to investigate whether the use of prompts can reduce the error rate in ECG interpretation among students.Method: In a 2x2 experimental test and control group design, N =100 final year medical students carried out ECG interpretation tasks in the form of online case vignettes in CASUS®. In these tasks, justification prompts (B) and error analysis prompts (F) were systematically varied in four groups and the learning success was measured using a knowledge test. In addition, prior knowledge in ECG interpretation, motivation, interest in the topic, subjective confidence in ECG interpretation, and cognitive load was collected.Results: Neither error analysis prompts nor justification prompts had a significant effect on the correct ECG interpretation by students, F (1,96)=1.03, p =.31. Justification prompts seemed to have a positive effect on the confidence of answering the questions, F (1,96)=10.15, p =.002, partial eta 2 =.10; and a negative effect on student motivation, F (1,96)=8.13 , p =.005, partial eta 2 =.08; but both with comparable diagnostic accuracy.Conclusion: The present study could not confirm the positive effects of prompts on the error rate in ECG interpretation reported in the literature but showed significant effects on subjective confidence and motivation which should be investigated in further studies., Zielsetzung: Die EKG-Befundung ist anfällig für Fehler, welche zu relevanten Fehldiagnosen und falschen Therapien führen können. Eine Möglichkeit, das Lernen aus eigenen Fehlern und die Reduktion der Fehlerrate im Rahmen von Lehrveranstaltungen zu fördern, sind Prompts. Prompts sind Maßnahmen, wie Fragen, Hinweise und Anregungen inhaltlicher oder metakognitiver Natur, die zur Selbsterklärung beim Lernenden und damit zu tieferem Verständnis eines Sachverhaltes führen können. Das Ziel der Studie war es daher, zu untersuchen, ob der Einsatz von Prompts die Fehlerrate Studierender bei der EKG-Befundung reduzieren kann.Methodik: In einem 2x2 experimentellen Versuchs-Kontrollgruppen Design bearbeiteten N =100 Medizinstudierende mit PJ-Reife Online-Fallvignetten in CASUS® mit EKG-Befundungsaufgaben. Dabei wurden Begründungsprompts (B) und Fehleranalyseprompts (F) in vier Gruppen systematisch variiert sowie der Lernerfolg in einem Wissenstest gemessen. Zusätzlich wurde das Vorwissen zur EKG- Befundung, Motivation, Interesse an der Thematik, subjektive Sicherheit bei der Befundung und Cognitive Load erhoben.Ergebnisse: Weder Fehleranalyseprompts noch Begründungsprompts hatten einen signifikanten Effekt auf die korrekte EKG-Befundung Studierender, F (1,96)=1.03, p =.31. Begründungsprompts schienen sich positiv auf die Sicherheit bei der Beantwortung der Aufgaben auszuwirken, F (1,96)=10.15, p =.002, partielles eta 2 =.10, und negativ auf die Motivation der Studierenden, F (1,96)=8.13, p =.005, partielles eta 2 =.08, beides jedoch bei vergleichbarer Befundungsrichtigkeit.Schlussfolgerung: Die vorliegende Studie konnte in der Literatur berichtete positive Effekte von Prompts auf die Fehlerrate bei der EKG-Befundung nicht bestätigen, zeigte jedoch signifikante Effekte auf die subjektive Sicherheit bei der Beantwortung und die Motivation, die es in weiterführenden Studien zu untersuchen gilt.
Published: 2020

25. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, I. (Ioanna), Weng, L.-C., Cartwright, J.H. (James H.), Hall, A.W. (Amelia Weber), Sveinbjornsson, G. (Gardar), Tucker, N.R. (Nathan R.), Choi, S.H. (Seung Hoan), Chaffin, M.D. (Mark D.), Roselli, C. (Carolina), Barnes, M.J. (Michael), Mifsud, B. (Borbala), Warren, H.R. (Helen R.), Hayward, C. (Caroline), Marten, J. (Jonathan), Cranley, J.J. (James J.), Concas, M.P. (Maria Pina), Gasparini, P. (Paolo), Boutin, T. (Thibaud), Kolcic, I. (Ivana), Polasek, O. (Ozren), Rudan, I. (Igor), Araujo, N.M. (Nathalia M.), Lima-Costa, M.F. (Maria Fernanda), Ribeiro, A.L. (Antonio), Souza, R.P. (Renan P.), Tarazona-Santos, E. (Eduardo), Giedraitis, V. (Vilmantas), Ingelsson, E. (Erik), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Del Greco M, F. (Fabiola), Foco, L. (Luisa), Gögele, M. (Martin), Hicks, A.A. (Andrew A.), Cook, J.P. (James P.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Sundström, J. (Johan), Nelson, C.P. (Christopher P.), Riaz, M.B. (Muhammad B.), Samani, N.J. (Nilesh), Sinagra, G. (Gianfranco), Ulivi, S. (Shelia), Kähönen, M. (Mika), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Nikus, K. (Kjell), Caulfield, M. (Mark), Dominiczak, A. (Anna), Padmanabhan, S. (Sandosh), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Ryan, K. (Kathleen), Shuldiner, A.R. (Alan R.), Aeschbacher, S. (Stefanie), Conen, D. (David), Risch, L. (Lorenz), Thériault, S. (Sébastien), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Lyytikäinen, L.-P. (Leo-Pekka), Raitakari, O. (Olli), Barnes, C.L.K. (Catriona L. K.), Campbell, H. (Harry), Joshi, P.K. (Peter), Wilson, J.F. (James), Isaacs, A.J. (Aaron), Kors, J.A. (Jan), Duijn, C.M. (Cornelia) van, Huang, P.L. (Paul L.), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara B.), Launer, L.J. (Lenore), Smith, A.V. (Albert), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Nadkarni, G. (Girish), Preuss, M. (Michael), Correa, D.D., Mei, H. (Hao), Meitinger, T. (Thomas), Müller-Nurasyid, M. (Martina), Peters, A. (Annette), Waldenberger, M. (Melanie), Mangino, M. (Massimo), Spector, T.D. (Timothy), Rienstra, S.A., van de Vegte, Y.J. (Yordi J.), Harst, P. (Pim) van der, Verweij, N. (Niek), Kääb, S. (Stefan), Schramm, K. (Katharina), Sinner, M.F. (Moritz), Strauch, K. (Konstantin), Cutler, M.J. (Michael J.), Fatkin, D. (Diane), London, B. (Barry), Olesen, M.S. (Morten S.), Roden, D.M. (Dan M.), Benjamin Shoemaker, M. (M.), Gustav Smith, J. (J.), Biggs, M.L. (M.), Bis, J.C. (Joshua), Brody, J.A. (Jennifer A.), Psaty, B.M. (Bruce), Rice, K.M. (Kenneth), Sotoodehnia, N. (Nona), Grandi, A. (Alessandro) de, Fuchsberger, C. (Christian), Penninx, B.W.J.H., Pramstaller, P.P. (Peter Paul), Ford, I. (Ian), Jukema, J.W. (Jan Wouter), Macfarlane, P.W. (Peter W.), Trompet, S. (Stella), Dörr, M. (Marcus), Felix, S.B. (Stephan B.), Völker, U. (Uwe), Weiss, S. (Stefan), Havulinna, A.S. (Aki), Jula, A. (Antti), Sääksjärvi, K. (K.), Salomaa, V. (Veikko), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Lin, H.J. (Henry J.), Rotter, J.I. (Jerome I.), Taylor, K.D. (Kent), Yao, J. (Jie), Mutsert, R. (Reneé) de, Maan, A.C. (Arie C.), Mook-Kanamori, D.O. (Dennis O.), Noordam, R. (Raymond), Cucca, F. (Francesco), Ding, J. (Jun), Lakatta, E. (Edward), Qian, Y. (Yong), Tarasov, K.V. (Kirill V.), Levy, D. (Daniel), Lin, H. (Honghuang), Newton-Cheh, C. (Christopher), Lunetta, K.L. (Kathryn), Murray, A.D. (Alison D.), Porteous, D.J. (David J.), Smith, B.H. (Blair), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Berg, M.E. (Marten) van den, Haessler, J. (Jeff), Jackson, R.D. (Rebecca), Kooperberg, C. (Charles), Peters, U. (Ulrike), Reiner, A.P. (Alexander P.), Whitsel, E.A. (Eric), Alonso, A. (Alvaro), Arking, D.E. (Dan E.), Boerwinkle, E.A. (Eric), Ehret, G.B. (Georg B.), Soliman, E.Z. (Elsayed Z.), Avery, C.L., Gogarten, S.M., Kerr, K.F. (Kathleen), Laurie, C.C. (Cathy C.), Seyerle, A.A. (Amanda A.), Stilp, A. (Adrienne), Assa, S. (Solmaz), Abdullah Said, M. (M.), Yldau van der Ende, M. (M.), Lambiase, P.D. (Pier), Orini, M. (Michele), Ramirez, J. (Julia), Van Duijvenboden, S. (Stefan), Arnar, D.O. (David O.), Gudbjartsson, D.F. (Daniel), Holm, H. (Hilma), Sulem, P. (Patrick), Thorleifsson, G. (Gudmar), Thorolfsdottir, R.B. (Rosa B.), Thorsteinsdottir, U. (Unnur), Benjamin, E.J. (Emelia J.), Tinker, A. (Andrew), Zwart, J-A. (John-Anker), Ellinor, P.T. (Patrick), Jamshidi, Y. (Yalda), Lubitz, S.A. (Steven), Munroe, P. (Patricia), Ntalla, I. (Ioanna), Weng, L.-C., Cartwright, J.H. (James H.), Hall, A.W. (Amelia Weber), Sveinbjornsson, G. (Gardar), Tucker, N.R. (Nathan R.), Choi, S.H. (Seung Hoan), Chaffin, M.D. (Mark D.), Roselli, C. (Carolina), Barnes, M.J. (Michael), Mifsud, B. (Borbala), Warren, H.R. (Helen R.), Hayward, C. (Caroline), Marten, J. (Jonathan), Cranley, J.J. (James J.), Concas, M.P. (Maria Pina), Gasparini, P. (Paolo), Boutin, T. (Thibaud), Kolcic, I. (Ivana), Polasek, O. (Ozren), Rudan, I. (Igor), Araujo, N.M. (Nathalia M.), Lima-Costa, M.F. (Maria Fernanda), Ribeiro, A.L. (Antonio), Souza, R.P. (Renan P.), Tarazona-Santos, E. (Eduardo), Giedraitis, V. (Vilmantas), Ingelsson, E. (Erik), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Del Greco M, F. (Fabiola), Foco, L. (Luisa), Gögele, M. (Martin), Hicks, A.A. (Andrew A.), Cook, J.P. (James P.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Sundström, J. (Johan), Nelson, C.P. (Christopher P.), Riaz, M.B. (Muhammad B.), Samani, N.J. (Nilesh), Sinagra, G. (Gianfranco), Ulivi, S. (Shelia), Kähönen, M. (Mika), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Nikus, K. (Kjell), Caulfield, M. (Mark), Dominiczak, A. (Anna), Padmanabhan, S. (Sandosh), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Ryan, K. (Kathleen), Shuldiner, A.R. (Alan R.), Aeschbacher, S. (Stefanie), Conen, D. (David), Risch, L. (Lorenz), Thériault, S. (Sébastien), Hutri-Kähönen, N. (Nina), Lehtimäki, T. (Terho), Lyytikäinen, L.-P. (Leo-Pekka), Raitakari, O. (Olli), Barnes, C.L.K. (Catriona L. K.), Campbell, H. (Harry), Joshi, P.K. (Peter), Wilson, J.F. (James), Isaacs, A.J. (Aaron), Kors, J.A. (Jan), Duijn, C.M. (Cornelia) van, Huang, P.L. (Paul L.), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara B.), Launer, L.J. (Lenore), Smith, A.V. (Albert), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Nadkarni, G. (Girish), Preuss, M. (Michael), Correa, D.D., Mei, H. (Hao), Meitinger, T. (Thomas), Müller-Nurasyid, M. (Martina), Peters, A. (Annette), Waldenberger, M. (Melanie), Mangino, M. (Massimo), Spector, T.D. (Timothy), Rienstra, S.A., van de Vegte, Y.J. (Yordi J.), Harst, P. (Pim) van der, Verweij, N. (Niek), Kääb, S. (Stefan), Schramm, K. (Katharina), Sinner, M.F. (Moritz), Strauch, K. (Konstantin), Cutler, M.J. (Michael J.), Fatkin, D. (Diane), London, B. (Barry), Olesen, M.S. (Morten S.), Roden, D.M. (Dan M.), Benjamin Shoemaker, M. (M.), Gustav Smith, J. (J.), Biggs, M.L. (M.), Bis, J.C. (Joshua), Brody, J.A. (Jennifer A.), Psaty, B.M. (Bruce), Rice, K.M. (Kenneth), Sotoodehnia, N. (Nona), Grandi, A. (Alessandro) de, Fuchsberger, C. (Christian), Penninx, B.W.J.H., Pramstaller, P.P. (Peter Paul), Ford, I. (Ian), Jukema, J.W. (Jan Wouter), Macfarlane, P.W. (Peter W.), Trompet, S. (Stella), Dörr, M. (Marcus), Felix, S.B. (Stephan B.), Völker, U. (Uwe), Weiss, S. (Stefan), Havulinna, A.S. (Aki), Jula, A. (Antti), Sääksjärvi, K. (K.), Salomaa, V. (Veikko), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Lin, H.J. (Henry J.), Rotter, J.I. (Jerome I.), Taylor, K.D. (Kent), Yao, J. (Jie), Mutsert, R. (Reneé) de, Maan, A.C. (Arie C.), Mook-Kanamori, D.O. (Dennis O.), Noordam, R. (Raymond), Cucca, F. (Francesco), Ding, J. (Jun), Lakatta, E. (Edward), Qian, Y. (Yong), Tarasov, K.V. (Kirill V.), Levy, D. (Daniel), Lin, H. (Honghuang), Newton-Cheh, C. (Christopher), Lunetta, K.L. (Kathryn), Murray, A.D. (Alison D.), Porteous, D.J. (David J.), Smith, B.H. (Blair), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Berg, M.E. (Marten) van den, Haessler, J. (Jeff), Jackson, R.D. (Rebecca), Kooperberg, C. (Charles), Peters, U. (Ulrike), Reiner, A.P. (Alexander P.), Whitsel, E.A. (Eric), Alonso, A. (Alvaro), Arking, D.E. (Dan E.), Boerwinkle, E.A. (Eric), Ehret, G.B. (Georg B.), Soliman, E.Z. (Elsayed Z.), Avery, C.L., Gogarten, S.M., Kerr, K.F. (Kathleen), Laurie, C.C. (Cathy C.), Seyerle, A.A. (Amanda A.), Stilp, A. (Adrienne), Assa, S. (Solmaz), Abdullah Said, M. (M.), Yldau van der Ende, M. (M.), Lambiase, P.D. (Pier), Orini, M. (Michele), Ramirez, J. (Julia), Van Duijvenboden, S. (Stefan), Arnar, D.O. (David O.), Gudbjartsson, D.F. (Daniel), Holm, H. (Hilma), Sulem, P. (Patrick), Thorleifsson, G. (Gudmar), Thorolfsdottir, R.B. (Rosa B.), Thorsteinsdottir, U. (Unnur), Benjamin, E.J. (Emelia J.), Tinker, A. (Andrew), Zwart, J-A. (John-Anker), Ellinor, P.T. (Patrick), Jamshidi, Y. (Yalda), Lubitz, S.A. (Steven), and Munroe, P. (Patricia)
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduc
Published: 2020
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26. Long QT syndrome: Why does sex matter?

Author: Kääb, S., Pfeufer, A., Hinterseer, M., Näbauer, M., and Schulze-Bahr, E.
Published: 2004
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27. 12-Kanal-EKG bei Brugada-Syndrom: Diagnostisch wegweisend bei einem Patienten mit Fieber und Synkope

Author: Götz, O., Beckmann, B., Kääb, S., and Hinterseer, M.
Published: 2009
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28. Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project

Author: Zabel, M., Schlögl, S., Lubinski, A., Svendsen, J. H., Bauer, A., Arbelo, E., Brusich, S., Conen, D., Cygankiewicz, I., Dommasch, M., Flevari, P., Galuszka, J., Hansen, J., Hasenfuß, G., Hatala, R., Huikuri, H. V., Kenttä, T., Kuczejko, T., Haarmann, H., Harden, M., Iovev, S., Kääb, S., Kaliska, G., Katsimardos, A., Kasprzak, J. D., Qavoq, D., Lüthje, L., Malik, M., Novotny, T., Pavlovic, N., Perge, P., Röver, C., Schmidt, G., Shalganov, T., Sritharan, R., Svetlosak, M., Sallo, Z., Szavits-Nossan, J., Traykov, V., Vandenberk, B., Velchec, V., Vos, M. A., Willich, S. N., Friede, T., Willems, R., Merkely, B., Sticherling, C., and investigators, the EU-CERT-ICD study
Subjects: FOS: Computer and information sciences, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, medicine.medical_specialty, Comparative Effectiveness Research, medicine.medical_treatment, Comparative effectiveness research, Review, Disease, 030204 cardiovascular system & hematology, Statistics - Applications, Sudden cardiac death, 03 medical and health sciences, Electrocardiography, Implantable cardioverter defibrillator, Mortality, Risk factors, 0302 clinical medicine, Journal Article, Clinical endpoint, Medicine, Humans, Multicenter Studies as Topic, Applications (stat.AP), 030212 general & internal medicine, Prospective Studies, business.industry, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Dilated cardiomyopathy, implantable cardioverter defibrillator, risk factors, mortality, sudden cardiac death, medicine.disease, Implantable cardioverter-defibrillator, 3. Good health, Defibrillators, Implantable, Europe, Observational Studies as Topic, Death, Sudden, Cardiac, Treatment Outcome, Heart failure, Emergency medicine, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract: BACKGROUND. The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue. SUMMARY. The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12-lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit. CONCLUSION. The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular., 22 pages, 3 figures
Published: 2019

29. Genetic Polymorphisms and Their Role in Ventricular Arrhythmias

Author: Kääb, S., primary, Näbauer, M., additional, and Pfeufer, A., additional
Published: 2002
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30. Evaluation of definitions and parameters for sepsis assessment in patients after cardiac surgery

Author: Pilz, G., Kääb, S., Werdan, K., and Kreuzer, E.
Published: 1994
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31. Long-QT-Syndrom: molekulare Grundlagen und Klinik

Author: Kääb, S., primary
Published: 1999
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32. Supplemental immunoglobulin (ivIgG) treatment in 163 patients with sepsis and septic shock — An observational study as a prerequisite for placebo-controlled clinical trials

Author: Pilz, G., Kääb, S., Werdan, K., Neeser, Gertraud, Class, Isolde, Schweigart, Ursula, Brähler, A., Bujdoso, O., and Neumann, Roswita
Published: 1991
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33. Five-year outcomes with PCI guided by fractional flow reserve

Author: Xaplanteris, P., Fournier, S., Pijls, N. H. J., Fearon, W. F., Barbato, E., Tonino, P. A. L., Engstrøm, T., Kääb, S., Dambrink, J. H., Toth, G. G., Rioufol, G., Piroth, Z., Witt, N., Fröbert, O., Kala, P., Linke, A., Jagic, N., Mates, M., Mavromatis, K., Samady, H., Irimpen, A., Oldroyd, K., Campo, G., Rothenbühler, M., Jüni, P., de Bruyne, B., Mulder, Barbara J. M., et al, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Department of Cardiology, Örebro University, Cardiovascular Biomechanics, Cardiology, APH - Personalized Medicine, APH - Aging & Later Life, ACS - Heart failure & arrhythmias, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), CarMeN, laboratoire, Xaplanteris, Panagioti, Fournier, Stephane, Pijls, Nico H J, Fearon, William F, Barbato, Emanuele, Tonino, Pim A L, Engstrøm, Thoma, Kääb, Stefan, Dambrink, Jan-Henk, Rioufol, Gille, Toth, Gabor G, Piroth, Zsolt, Witt, Nil, Fröbert, Ole, Kala, Petr, Linke, Axel, Jagic, Nicola, Mates, Martin, Mavromatis, Kreton, Samady, Habib, Irimpen, Anand, Oldroyd, Keith, Campo, Gianluca, Rothenbühler, Martina, Jüni, Peter, and De Bruyne, Bernard
Subjects: st-segment elevation, Male, task-force, Coronary Stenosi, Platelet Aggregation Inhibitors/therapeutic use, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Myocardial Infarction, Coronary Disease, Fractional flow reserve, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, Drug-Eluting Stent, 030212 general & internal medicine, Myocardial infarction, guidelines, Medicine (all), Angina Pectori, Hazard ratio, Drug-Eluting Stents, General Medicine, Middle Aged, Fractional Flow Reserve, myocardial-infarction, 3. Good health, [SDV] Life Sciences [q-bio], Fractional Flow Reserve, Myocardial, Antihypertensive Agent, Coronary Disease/drug therapy, Aged, Angina Pectoris, Antihypertensive Agents, Coronary Stenosis, Female, Follow-Up Studies, Humans, Platelet Aggregation Inhibitors, Retreatment, Percutaneous Coronary Intervention, Cardiology, Platelet aggregation inhibitor, management, Human, medicine.medical_specialty, Angina Pectoris/therapy, conservative treatment, Revascularization, Follow-Up Studie, european-society, NO, 03 medical and health sciences, Internal medicine, General & Internal Medicine, medicine, Myocardial Infarction/epidemiology, Myocardial, coronary, Antihypertensive Agents/therapeutic use, business.industry, Platelet Aggregation Inhibitor, prospective natural-history, Percutaneous coronary intervention, medicine.disease, medical therapy, Retreatment/statistics & numerical data, Conventional PCI, Coronary Stenosis/drug therapy, business
Abstract: Background: we hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease.Methods: among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.Results: a total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; PConclusions: in patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).
Published: 2018

34. Extrakorporale Therapieverfahren: Möglichkeiten und klinische Relevanz bei Patienten mit septischem Multiorganversagen

Author: Kääb, S., primary, Pilz, G., additional, Appel, R., additional, Samtleben, W., additional, Gurland, H. J., additional, and Werdan, K., additional
Published: 1992
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35. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

Author: Bihlmeyer, N.A. (Nathan A.), Brody, J.A. (Jennifer A.), Smith, A.V. (Albert), Warren, H. (Helen), Lin, H. (Honghuang), Isaacs, A. (Aaron), Liu, C.-T. (Ching-Ti), Marten, J. (Jonathan), Radmanesh, F. (Farid), Hall, L.M. (Leanne M.), Grarup, N. (Niels), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Huffman, J.E. (Jennifer E.), Verweij, N. (Niek), Guo, X. (Xiuqing), Yao, J. (Jie), Li-Gao, R. (Ruifang), Berg, M.E. (Marten) van den, Weiss, S. (Stefan), Prins, B.P. (Bram P.), Setten, J. (Jessica) van, Haessler, J. (Jeff), Lyytikäinen, L.-P. (Leo-Pekka), Li, M. (Man), Alonso, A. (Alvaro), Soliman, E.Z. (Elsayed Z.), Bis, J.C. (Joshua), Austin, T. (Tom), Chen, Y.D.I. (Yii-Der Ida), Psaty, B.M. (Bruce M.), Harrris, T.B. (Tamara B.), Launer, L.J. (Lenore), Padmanabhan, S. (Sandosh), Dominiczak, A. (Anna), Huang, P.L. (Paul L.), Xie, Z. (Zhijun), Ellinor, P.T. (Patrick), Kors, J.A. (Jan), Campbell, A. (Archie), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Tobin, M.D. (Martin), Bork-Jensen, J. (Jette), Hansen, T. (Torben), Pedersen, O. (Oluf), Linneberg, A. (Allan), Sinner, M.F. (Moritz), Peters, A. (Annette), Waldenberger, M. (Melanie), Meitinger, T. (Thomas), Perz, S. (Siegfried), Kolcic, I. (Ivana), Rudan, I. (Igor), Boer, R.A. (Rudolf) de, Meer, P. (Peter) van der, Lin, H.J. (Henry J.), Taylor, K.D. (Kent), Mutsert, R. (Reneé) de, Trompet, S. (Stella), Jukema, J.W. (Jan Wouter), Maan, A.C. (Arie C.), Stricker, B.H.Ch. (Bruno), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A. (André), Völker, U. (Uwe), Homuth, G. (Georg), Völzke, H. (Henry), Felix, S.B. (Stephan), Mangino, M. (Massimo), Spector, T.D. (Timothy), Bots, M.L. (Michiel), Perez, M. (Marco), Raitakari, O. (Olli), Kähönen, M. (Mika), Mononen, N. (Nina), Gudnason, V. (Vilmundur), Munroe, P. (Patricia), Lubitz, S.A. (Steven A.), Duijn, C.M. (Cornelia) van, Newton-Cheh, C. (Christopher), Hayward, C. (Caroline), Rosand, J. (Jonathan), Samani, N.J. (Nilesh J.), Kanters, J.K., Wilson, J.F. (James), Kääb, S. (Stefan), Polasek, O. (Ozren), van der Harst, P. (Pim), Heckbert, S.R. (Susan), Rotter, J.I. (Jerome I.), Mook-Kanamori, D.O. (Dennis O.), Eijgelsheim, M. (Mark), Dörr, M. (Marcus), Jamshidi, Y. (Yalda), Asselbergs, F.W. (Folkert W.), Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Arking, D.E. (Dan), Sotoodehnia, N. (Nona), Bihlmeyer, N.A. (Nathan A.), Brody, J.A. (Jennifer A.), Smith, A.V. (Albert), Warren, H. (Helen), Lin, H. (Honghuang), Isaacs, A. (Aaron), Liu, C.-T. (Ching-Ti), Marten, J. (Jonathan), Radmanesh, F. (Farid), Hall, L.M. (Leanne M.), Grarup, N. (Niels), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Huffman, J.E. (Jennifer E.), Verweij, N. (Niek), Guo, X. (Xiuqing), Yao, J. (Jie), Li-Gao, R. (Ruifang), Berg, M.E. (Marten) van den, Weiss, S. (Stefan), Prins, B.P. (Bram P.), Setten, J. (Jessica) van, Haessler, J. (Jeff), Lyytikäinen, L.-P. (Leo-Pekka), Li, M. (Man), Alonso, A. (Alvaro), Soliman, E.Z. (Elsayed Z.), Bis, J.C. (Joshua), Austin, T. (Tom), Chen, Y.D.I. (Yii-Der Ida), Psaty, B.M. (Bruce M.), Harrris, T.B. (Tamara B.), Launer, L.J. (Lenore), Padmanabhan, S. (Sandosh), Dominiczak, A. (Anna), Huang, P.L. (Paul L.), Xie, Z. (Zhijun), Ellinor, P.T. (Patrick), Kors, J.A. (Jan), Campbell, A. (Archie), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Tobin, M.D. (Martin), Bork-Jensen, J. (Jette), Hansen, T. (Torben), Pedersen, O. (Oluf), Linneberg, A. (Allan), Sinner, M.F. (Moritz), Peters, A. (Annette), Waldenberger, M. (Melanie), Meitinger, T. (Thomas), Perz, S. (Siegfried), Kolcic, I. (Ivana), Rudan, I. (Igor), Boer, R.A. (Rudolf) de, Meer, P. (Peter) van der, Lin, H.J. (Henry J.), Taylor, K.D. (Kent), Mutsert, R. (Reneé) de, Trompet, S. (Stella), Jukema, J.W. (Jan Wouter), Maan, A.C. (Arie C.), Stricker, B.H.Ch. (Bruno), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A. (André), Völker, U. (Uwe), Homuth, G. (Georg), Völzke, H. (Henry), Felix, S.B. (Stephan), Mangino, M. (Massimo), Spector, T.D. (Timothy), Bots, M.L. (Michiel), Perez, M. (Marco), Raitakari, O. (Olli), Kähönen, M. (Mika), Mononen, N. (Nina), Gudnason, V. (Vilmundur), Munroe, P. (Patricia), Lubitz, S.A. (Steven A.), Duijn, C.M. (Cornelia) van, Newton-Cheh, C. (Christopher), Hayward, C. (Caroline), Rosand, J. (Jonathan), Samani, N.J. (Nilesh J.), Kanters, J.K., Wilson, J.F. (James), Kääb, S. (Stefan), Polasek, O. (Ozren), van der Harst, P. (Pim), Heckbert, S.R. (Susan), Rotter, J.I. (Jerome I.), Mook-Kanamori, D.O. (Dennis O.), Eijgelsheim, M. (Mark), Dörr, M. (Marcus), Jamshidi, Y. (Yalda), Asselbergs, F.W. (Folkert W.), Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Arking, D.E. (Dan), and Sotoodehnia, N. (Nona)
Abstract: BACKGROUND: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest. METHODS AND RESULTS: We performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci. CONCLUSIONS: Our analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.
Published: 2018
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36. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author: Setten, J. (Jessica) van, Brody, J.A. (Jennifer A.), Jamshidi, Y. (Yalda), Swenson, B.R. (Brenton R.), Butler, A.M. (Anne M.), Campbell, H. (Harry), Del Greco, F.M. (Fabiola), Evans, D.S. (Daniel), Gibson, Q. (Quince), Gudbjartsson, D.F. (Daniel), Kerr, K.F. (Kathleen), Krijthe, B.P. (Bouwe), Lyytikäinen, L.-P. (Leo-Pekka), Müller, C. (Christian), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Ritchie, M.D. (Marylyn D.), Robino, A. (Antonietta), Smith, A.V. (Albert), Steri, M. (Maristella), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Ulivi, S. (Sheila), Verweij, N. (Niek), Yin, X. (Xiaoyan), Arnar, D.O. (David O.), Asselbergs, F.W. (Folkert W.), Bader, J.S. (Joel), Barnard, J. (John), Bis, J.C. (Joshua), Blankenberg, S. (Stefan), Boerwinkle, E. (Eric), Bradford, Y. (Yuki), Buckley, B.M. (Brendan M.), Chung, M.K. (Mina), Crawford, D. (Dana), Hoed, M. (Marcel) den, Denny, J.C. (Joshua C.), Dominiczak, A. (Anna), Ehret, G.B. (Georg B.), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Felix, S.B. (Stephan), Franco, O.H. (Oscar), Franke, L. (Lude), Harris, T.B. (Tamara), Holm, H. (Hilma), Ilaria, G. (Gandin), Iorio, A. (Annamaria), Kähönen, M. (Mika), Kolcic, I. (Ivana), Kors, J.A. (Jan), Lakatta, E. (Edward), Launer, L.J. (Lenore), Lin, H. (Honghuang), Lin, H.J. (Henry J.), Loos, R.J.F. (Ruth), Lubitz, S.A. (Steven A.), MacFarlane, P.W. (Peter), Magnani, J.W. (Jared), Leach, I.M. (Irene Mateo), Meitinger, T. (Thomas), Mitchell, B.D. (Braxton), Munzel, T. (Thomas), Papanicolaou, G.J. (George J.), Peters, A. (Annette), Pfeufer, A. (Arne), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Schlessinger, D. (David), Silva Aldana, C.T. (Claudia), Sinner, M.F. (Moritz), Smith, J.D. (Jonathan), Snieder, H. (Harold), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Stott, D.J. (David. J.), Strauch, K. (Konstantin), Tarasov, K.V. (Kirill V.), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Wagoner, D.R. (David) van, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Jan Westra, H. (Harm), Wild, P.S. (Philipp), Zeller, T. (Tanja), Alonso, A. (Alvaro), Avery, C.L., Bandinelli, S. (Stefania), Benjamin, E.J. (Emelia), Cucca, F. (Francesco), Dörr, M. (Marcus), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Gudnason, V. (Vilmundur), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Hicks, A.A. (Andrew A.), Jukema, J.W. (Jan Wouter), Kääb, S. (Stefan), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Munroe, P. (Patricia), Parsa, A. (Afshin), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Roden, D.M. (Dan), Schnabel, R.B. (Renate), Sinagra, G. (Gianfranco), Zwart, J-A. (John-Anker), Stricker, B.H.Ch. (Bruno), van der Harst, P. (Pim), Duijn, C.M. (Cornelia) van, Wilson, J.F. (James F.), Gharib, S.A. (Sina), Bakker, P.I.W. (Paul) de, Isaacs, A. (Aaron), Arking, D.E. (Dan), Sotoodehnia, N. (Nona), Setten, J. (Jessica) van, Brody, J.A. (Jennifer A.), Jamshidi, Y. (Yalda), Swenson, B.R. (Brenton R.), Butler, A.M. (Anne M.), Campbell, H. (Harry), Del Greco, F.M. (Fabiola), Evans, D.S. (Daniel), Gibson, Q. (Quince), Gudbjartsson, D.F. (Daniel), Kerr, K.F. (Kathleen), Krijthe, B.P. (Bouwe), Lyytikäinen, L.-P. (Leo-Pekka), Müller, C. (Christian), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Ritchie, M.D. (Marylyn D.), Robino, A. (Antonietta), Smith, A.V. (Albert), Steri, M. (Maristella), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Ulivi, S. (Sheila), Verweij, N. (Niek), Yin, X. (Xiaoyan), Arnar, D.O. (David O.), Asselbergs, F.W. (Folkert W.), Bader, J.S. (Joel), Barnard, J. (John), Bis, J.C. (Joshua), Blankenberg, S. (Stefan), Boerwinkle, E. (Eric), Bradford, Y. (Yuki), Buckley, B.M. (Brendan M.), Chung, M.K. (Mina), Crawford, D. (Dana), Hoed, M. (Marcel) den, Denny, J.C. (Joshua C.), Dominiczak, A. (Anna), Ehret, G.B. (Georg B.), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Felix, S.B. (Stephan), Franco, O.H. (Oscar), Franke, L. (Lude), Harris, T.B. (Tamara), Holm, H. (Hilma), Ilaria, G. (Gandin), Iorio, A. (Annamaria), Kähönen, M. (Mika), Kolcic, I. (Ivana), Kors, J.A. (Jan), Lakatta, E. (Edward), Launer, L.J. (Lenore), Lin, H. (Honghuang), Lin, H.J. (Henry J.), Loos, R.J.F. (Ruth), Lubitz, S.A. (Steven A.), MacFarlane, P.W. (Peter), Magnani, J.W. (Jared), Leach, I.M. (Irene Mateo), Meitinger, T. (Thomas), Mitchell, B.D. (Braxton), Munzel, T. (Thomas), Papanicolaou, G.J. (George J.), Peters, A. (Annette), Pfeufer, A. (Arne), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Schlessinger, D. (David), Silva Aldana, C.T. (Claudia), Sinner, M.F. (Moritz), Smith, J.D. (Jonathan), Snieder, H. (Harold), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Stott, D.J. (David. J.), Strauch, K. (Konstantin), Tarasov, K.V. (Kirill V.), Thorsteinsdottir, U. (Unnur), Uitterlinden, A.G. (André), Wagoner, D.R. (David) van, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Jan Westra, H. (Harm), Wild, P.S. (Philipp), Zeller, T. (Tanja), Alonso, A. (Alvaro), Avery, C.L., Bandinelli, S. (Stefania), Benjamin, E.J. (Emelia), Cucca, F. (Francesco), Dörr, M. (Marcus), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Gudnason, V. (Vilmundur), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Hicks, A.A. (Andrew A.), Jukema, J.W. (Jan Wouter), Kääb, S. (Stefan), Lehtimäki, T. (Terho), Liu, Y. (YongMei), Munroe, P. (Patricia), Parsa, A. (Afshin), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Roden, D.M. (Dan), Schnabel, R.B. (Renate), Sinagra, G. (Gianfranco), Zwart, J-A. (John-Anker), Stricker, B.H.Ch. (Bruno), van der Harst, P. (Pim), Duijn, C.M. (Cornelia) van, Wilson, J.F. (James F.), Gharib, S.A. (Sina), Bakker, P.I.W. (Paul) de, Isaacs, A. (Aaron), Arking, D.E. (Dan), and Sotoodehnia, N. (Nona)
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Published: 2018
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37. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, B.P. (Bram P.), Mead, T.J. (Timothy J.), Brody, J.A. (Jennifer A.), Sveinbjornsson, G. (Gardar), Ntalla, I. (Ioanna), Bihlmeyer, N.A. (Nathan A.), Berg, M.E. (Marten) van den, Bork-Jensen, J. (Jette), Cappellani, S. (Stefania), Van Duijvenboden, S. (Stefan), Klena, N.T. (Nikolai T.), Gabriel, G.C. (George C.), Liu, X. (Xiaoqin), Gulec, C. (Cagri), Grarup, N. (Niels), Haessler, J. (Jeff), Hall, L.M. (Leanne M.), Iorio, A. (Annamaria), Isaacs, A. (Aaron), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Liu, C.-T. (Ching-Ti), Lyytikäinen, L.-P. (Leo-Pekka), Marten, J. (Jonathan), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Orini, M. (Michele), Padmanabhan, S. (Sandosh), Radmanesh, F. (Farid), Ramirez, J. (Julia), Robino, A. (Antonietta), Schwartz, M. (Molly), Setten, J. (Jessica) van, Smith, A.V. (Albert), Verweij, N. (Niek), Warren, H. (Helen), Weiss, S. (Stefan), Alonso, A. (Alvaro), Arnar, D.O. (David O.), Bots, M.L. (Michiel), Boer, R.A. (Rudolf) de, Dominiczak, A. (Anna), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Guo, X. (Xiuqing), Felix, S.B. (Stephan), Harris, T.B. (Tamara), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kors, J.A. (Jan), Lambiase, P.D. (Pier), Launer, L.J. (Lenore), Li, M. (Man), Linneberg, A. (Allan), Nelson, C.P. (Christopher P.), Pedersen, O. (Oluf), Perez, M. (Marco), Peters, A. (Annette), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Raitakari, O. (Olli), Rice, K.M. (Kenneth), Rotter, J.I. (Jerome I.), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Strauch, K. (Konstantin), Thorsteinsdottir, U. (Unnur), Tinker, A. (Andrew), Trompet, S. (Stella), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Meer, P. (Peter) van der, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Wilson, J.F. (James), Xie, Z. (Zhijun), Asselbergs, F.W. (Folkert W.), Dörr, M. (Marcus), Duijn, C.M. (Cornelia) van, Gasparini, P. (Paolo), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Hansen, T. (Torben), Kääb, S. (Stefan), Kanters, J.K., Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Lin, H.J. (Henry J.), Lubitz, S.A. (Steven A.), Mook-Kanamori, D.O. (Dennis O.), Conti, F.J. (Francesco J.), Newton-Cheh, C. (Christopher), Rosand, J. (Jonathan), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Sinagra, G. (Gianfranco), Smith, B.H. (Blair), Holm, H. (Hilma), Stricker, B.H.Ch. (Bruno), Ulivi, S. (Sheila), Sotoodehnia, N. (Nona), Apte, S.S. (Suneel S.), van der Harst, P. (Pim), Zwart, J-A. (John-Anker), Munroe, P. (Patricia), Arking, D.E. (Dan), Lo, C.W. (Cecilia W.), Jamshidi, Y. (Yalda), Prins, B.P. (Bram P.), Mead, T.J. (Timothy J.), Brody, J.A. (Jennifer A.), Sveinbjornsson, G. (Gardar), Ntalla, I. (Ioanna), Bihlmeyer, N.A. (Nathan A.), Berg, M.E. (Marten) van den, Bork-Jensen, J. (Jette), Cappellani, S. (Stefania), Van Duijvenboden, S. (Stefan), Klena, N.T. (Nikolai T.), Gabriel, G.C. (George C.), Liu, X. (Xiaoqin), Gulec, C. (Cagri), Grarup, N. (Niels), Haessler, J. (Jeff), Hall, L.M. (Leanne M.), Iorio, A. (Annamaria), Isaacs, A. (Aaron), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Liu, C.-T. (Ching-Ti), Lyytikäinen, L.-P. (Leo-Pekka), Marten, J. (Jonathan), Mei, H. (Hao), Müller-Nurasyid, M. (Martina), Orini, M. (Michele), Padmanabhan, S. (Sandosh), Radmanesh, F. (Farid), Ramirez, J. (Julia), Robino, A. (Antonietta), Schwartz, M. (Molly), Setten, J. (Jessica) van, Smith, A.V. (Albert), Verweij, N. (Niek), Warren, H. (Helen), Weiss, S. (Stefan), Alonso, A. (Alvaro), Arnar, D.O. (David O.), Bots, M.L. (Michiel), Boer, R.A. (Rudolf) de, Dominiczak, A. (Anna), Eijgelsheim, M. (Mark), Ellinor, P.T. (Patrick), Guo, X. (Xiuqing), Felix, S.B. (Stephan), Harris, T.B. (Tamara), Hayward, C. (Caroline), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kors, J.A. (Jan), Lambiase, P.D. (Pier), Launer, L.J. (Lenore), Li, M. (Man), Linneberg, A. (Allan), Nelson, C.P. (Christopher P.), Pedersen, O. (Oluf), Perez, M. (Marco), Peters, A. (Annette), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Raitakari, O. (Olli), Rice, K.M. (Kenneth), Rotter, J.I. (Jerome I.), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed Z.), Spector, T.D. (Timothy), Strauch, K. (Konstantin), Thorsteinsdottir, U. (Unnur), Tinker, A. (Andrew), Trompet, S. (Stella), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Meer, P. (Peter) van der, Völker, U. (Uwe), Völzke, H. (Henry), Waldenberger, M. (Melanie), Wilson, J.F. (James), Xie, Z. (Zhijun), Asselbergs, F.W. (Folkert W.), Dörr, M. (Marcus), Duijn, C.M. (Cornelia) van, Gasparini, P. (Paolo), Gudbjartsson, D.F. (Daniel), Gudnason, V. (Vilmundur), Hansen, T. (Torben), Kääb, S. (Stefan), Kanters, J.K., Kooperberg, C. (Charles), Lehtimäki, T. (Terho), Lin, H.J. (Henry J.), Lubitz, S.A. (Steven A.), Mook-Kanamori, D.O. (Dennis O.), Conti, F.J. (Francesco J.), Newton-Cheh, C. (Christopher), Rosand, J. (Jonathan), Rudan, I. (Igor), Samani, N.J. (Nilesh J.), Sinagra, G. (Gianfranco), Smith, B.H. (Blair), Holm, H. (Hilma), Stricker, B.H.Ch. (Bruno), Ulivi, S. (Sheila), Sotoodehnia, N. (Nona), Apte, S.S. (Suneel S.), van der Harst, P. (Pim), Zwart, J-A. (John-Anker), Munroe, P. (Patricia), Arking, D.E. (Dan), Lo, C.W. (Cecilia W.), and Jamshidi, Y. (Yalda)
Abstract: Background: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. Results: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. Conclusions: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.
Published: 2018
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38. Fifteen Genetic Loci Associated with the Electrocardiographic P Wave

Author: Christophersen, I.E. (Ingrid E.), Magnani, J.W. (Jared), Yin, X. (Xiaoyan), Barnard, J. (John), Weng, L.-C., Arking, D.E. (Dan E.), Niemeijer, M.N. (Maartje), Lubitz, S.A. (Steven), Avery, C.L., Duan, Q. (Qing), Felix, S.B. (Stephan B.), Bis, J.C. (Joshua), Kerr, K.F. (Kathleen), Isaacs, A.J. (Aaron), Müller-Nurasyid, M. (Martina), Müller, C. (Christian), North, K.E. (Kari), Reiner, A. (Alexander), Tinker, L.F. (Lesley F.), Kors, J.A. (Jan), Teumer, A. (Alexander), Petersmann, A. (Astrid), Sinner, M.F. (Moritz), Buzkova, P. (Petra), Smith, J.D. (Jonathan), Wagoner, D.R. (David) van, Völker, U. (Uwe), Waldenberger, M. (Melanie), Peters, A. (Annette), Meitinger, T. (Thomas), Limacher, M.C. (Marian C.), Wilhelmsen, K.C., Psaty, B.M. (Bruce M.), Hofman, A. (Albert), Uitterlinden, A.G. (André), Krijthe, B.P. (Bouwe P.), Zhang, Z. (Z.), Schnabel, R.B. (Renate), Kääb, S. (Stefan), Duijn, C.M. (Cornelia) van, Rotter, J.I. (Jerome I.), Sotoodehnia, N. (Nona), Dörr, M. (Marcus), Li, Y. (Yun), Chung, M.K. (Mina), Soliman, E.Z. (Elsayed Z.), Alonso, A. (Alvaro), Whitsel, E.A. (Eric), Stricker, B.H.Ch. (Bruno), Benjamin, E.J. (Emelia J.), Heckbert, S.R. (Susan), Ellinor, P.T. (Patrick), Christophersen, I.E. (Ingrid E.), Magnani, J.W. (Jared), Yin, X. (Xiaoyan), Barnard, J. (John), Weng, L.-C., Arking, D.E. (Dan E.), Niemeijer, M.N. (Maartje), Lubitz, S.A. (Steven), Avery, C.L., Duan, Q. (Qing), Felix, S.B. (Stephan B.), Bis, J.C. (Joshua), Kerr, K.F. (Kathleen), Isaacs, A.J. (Aaron), Müller-Nurasyid, M. (Martina), Müller, C. (Christian), North, K.E. (Kari), Reiner, A. (Alexander), Tinker, L.F. (Lesley F.), Kors, J.A. (Jan), Teumer, A. (Alexander), Petersmann, A. (Astrid), Sinner, M.F. (Moritz), Buzkova, P. (Petra), Smith, J.D. (Jonathan), Wagoner, D.R. (David) van, Völker, U. (Uwe), Waldenberger, M. (Melanie), Peters, A. (Annette), Meitinger, T. (Thomas), Limacher, M.C. (Marian C.), Wilhelmsen, K.C., Psaty, B.M. (Bruce M.), Hofman, A. (Albert), Uitterlinden, A.G. (André), Krijthe, B.P. (Bouwe P.), Zhang, Z. (Z.), Schnabel, R.B. (Renate), Kääb, S. (Stefan), Duijn, C.M. (Cornelia) van, Rotter, J.I. (Jerome I.), Sotoodehnia, N. (Nona), Dörr, M. (Marcus), Li, Y. (Yun), Chung, M.K. (Mina), Soliman, E.Z. (Elsayed Z.), Alonso, A. (Alvaro), Whitsel, E.A. (Eric), Stricker, B.H.Ch. (Bruno), Benjamin, E.J. (Emelia J.), Heckbert, S.R. (Susan), and Ellinor, P.T. (Patrick)
Abstract: The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies. Methods and Results - We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (P<5×10-8) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction. Conclusions - We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.
Published: 2017
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39. Discovery of novel heart rate-associated loci using the Exome Chip

Author: Berg, M.E. (Marten) van den, Warren, H. (Helen), Cabrera, C.P. (Claudia P.), Verweij, N. (Niek), Mifsud, B. (Borbala), Haessler, J. (Jeff), Bihlmeyer, N.A. (Nathan A.), Fu, Y.-P. (Yi-Ping), Weiss, S. (Stefan), Lin, H.J. (Henry J.), Grarup, N. (Niels), Li-Gao, R. (Ruifang), Pistis, G. (Giorgio), Shah, N. (Nisha), Brody, J.A. (Jennifer A.), Müller-Nurasyid, M. (Martina), Lin, H. (Honghuang), Mei, H. (Hao), Smith, A.V. (Albert V.), Lyytikäinen, L.-P. (Leo-Pekka), Hall, L.M. (Leanne M.), Setten, J. (Jessica) van, Trompet, S. (Stella), Prins, B.P. (Bram P.), Isaacs, A.J. (Aaron), Radmanesh, F. (Farid), Marten, J. (Jonathan), Entwistle, A. (Aiman), Kors, J.A. (Jan), Silva Aldana, C.T. (Claudia), Alonso, A. (Alvaro), Bis, J.C. (Joshua), Boer, R.A. (Rudolf) de, Haan, H.G. (Hugoline) de, Mutsert, R. (Reneé) de, Dedoussis, G.V. (George), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ellinor, P.T. (Patrick), Eppinga, R.N. (Ruben N.), Felix, S.B. (Stephan), Guo, X. (Xiuqing), Hagemeijer, Y. (Yanick), Hansen, T. (T.), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Hwang, S.-J. (Shih-Jen), Kähönen, M. (Mika), Kanters, J.K., Kolcic, I. (Ivana), Launer, L.J. (Lenore), Li, M. (Man), Yao, J. (Jiefen), Linneberg, A. (Allan), Liu, S. (Simin), MacFarlane, P.W. (Peter), Mangino, M. (Massimo), Morris, A.D. (Andrew D.), Mulas, A. (Antonella), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Orrù, M. (Marco), Padmanabhan, S. (Sandosh), Peters, A. (Annette), Porteous, D.J. (David J.), Poulter, N.R. (Neil), Psaty, B.M. (Bruce M.), Qi, L. (Lihong), Raitakari, O.T. (Olli T.), Rivadeneira, F. (Fernando), Roselli, C. (Carolina), Rudan, I. (Igor), Sattar, N. (Naveed), Sever, P. (Peter), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed), Spector, T.D. (Timothy), Stanton, A. (Alice), Stirrups, K. (Kathy), Taylor, K.D. (Kent), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Hoes, A.W. (Arno), van der Meer, P. (Peter), Völker, U. (Uwe), Waldenberger, M. (Melanie), Xie, Z. (Zhijun), Zoledziewska, M. (Magdalena), Tinker, A. (Andrew), Polasek, O. (Ozren), Rosand, J. (Jonathan), Jamshidi, Y. (Yalda), Duijn, C.M. (Cornelia) van, Zeggini, E. (Eleftheria), Jukema, J.W. (Jan Wouter), Asselbergs, F.W. (Folkert), Samani, N.J. (Nilesh), Lehtimäki, T. (Terho), Gudnason, V. (Vilmundur), Wilson, J.F. (James), Lubitz, S.A. (Steven A.), Kääb, S. (Stefan), Sotoodehnia, N. (Nona), Caulfield, M. (Mark), Palmer, C.N.A. (Colin), Sanna, S. (Serena), Mook-Kanamori, D.O. (Dennis), Deloukas, P. (Panos), Pedersen, O. (Oluf), Rotter, J.I. (Jerome I.), Dörr, M. (Marcus), O'Donnell, C.J. (Christopher J.), Hayward, C. (Caroline), Arking, D.E. (Dan), Kooperberg, C. (Charles), van der Harst, P. (Pim), Eijgelsheim, M. (Mark), Stricker, B.H.Ch. (Bruno), Munroe, P. (Patricia), Berg, M.E. (Marten) van den, Warren, H. (Helen), Cabrera, C.P. (Claudia P.), Verweij, N. (Niek), Mifsud, B. (Borbala), Haessler, J. (Jeff), Bihlmeyer, N.A. (Nathan A.), Fu, Y.-P. (Yi-Ping), Weiss, S. (Stefan), Lin, H.J. (Henry J.), Grarup, N. (Niels), Li-Gao, R. (Ruifang), Pistis, G. (Giorgio), Shah, N. (Nisha), Brody, J.A. (Jennifer A.), Müller-Nurasyid, M. (Martina), Lin, H. (Honghuang), Mei, H. (Hao), Smith, A.V. (Albert V.), Lyytikäinen, L.-P. (Leo-Pekka), Hall, L.M. (Leanne M.), Setten, J. (Jessica) van, Trompet, S. (Stella), Prins, B.P. (Bram P.), Isaacs, A.J. (Aaron), Radmanesh, F. (Farid), Marten, J. (Jonathan), Entwistle, A. (Aiman), Kors, J.A. (Jan), Silva Aldana, C.T. (Claudia), Alonso, A. (Alvaro), Bis, J.C. (Joshua), Boer, R.A. (Rudolf) de, Haan, H.G. (Hugoline) de, Mutsert, R. (Reneé) de, Dedoussis, G.V. (George), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ellinor, P.T. (Patrick), Eppinga, R.N. (Ruben N.), Felix, S.B. (Stephan), Guo, X. (Xiuqing), Hagemeijer, Y. (Yanick), Hansen, T. (T.), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Hwang, S.-J. (Shih-Jen), Kähönen, M. (Mika), Kanters, J.K., Kolcic, I. (Ivana), Launer, L.J. (Lenore), Li, M. (Man), Yao, J. (Jiefen), Linneberg, A. (Allan), Liu, S. (Simin), MacFarlane, P.W. (Peter), Mangino, M. (Massimo), Morris, A.D. (Andrew D.), Mulas, A. (Antonella), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Orrù, M. (Marco), Padmanabhan, S. (Sandosh), Peters, A. (Annette), Porteous, D.J. (David J.), Poulter, N.R. (Neil), Psaty, B.M. (Bruce M.), Qi, L. (Lihong), Raitakari, O.T. (Olli T.), Rivadeneira, F. (Fernando), Roselli, C. (Carolina), Rudan, I. (Igor), Sattar, N. (Naveed), Sever, P. (Peter), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed), Spector, T.D. (Timothy), Stanton, A. (Alice), Stirrups, K. (Kathy), Taylor, K.D. (Kent), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Hoes, A.W. (Arno), van der Meer, P. (Peter), Völker, U. (Uwe), Waldenberger, M. (Melanie), Xie, Z. (Zhijun), Zoledziewska, M. (Magdalena), Tinker, A. (Andrew), Polasek, O. (Ozren), Rosand, J. (Jonathan), Jamshidi, Y. (Yalda), Duijn, C.M. (Cornelia) van, Zeggini, E. (Eleftheria), Jukema, J.W. (Jan Wouter), Asselbergs, F.W. (Folkert), Samani, N.J. (Nilesh), Lehtimäki, T. (Terho), Gudnason, V. (Vilmundur), Wilson, J.F. (James), Lubitz, S.A. (Steven A.), Kääb, S. (Stefan), Sotoodehnia, N. (Nona), Caulfield, M. (Mark), Palmer, C.N.A. (Colin), Sanna, S. (Serena), Mook-Kanamori, D.O. (Dennis), Deloukas, P. (Panos), Pedersen, O. (Oluf), Rotter, J.I. (Jerome I.), Dörr, M. (Marcus), O'Donnell, C.J. (Christopher J.), Hayward, C. (Caroline), Arking, D.E. (Dan), Kooperberg, C. (Charles), van der Harst, P. (Pim), Eijgelsheim, M. (Mark), Stricker, B.H.Ch. (Bruno), and Munroe, P. (Patricia)
Abstract: Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.
Published: 2017
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40. Expert consensus document: Defining the major health modifiers causing atrial fibrillation: a roadmap to underpin personalized prevention and treatment

Author: Fabritz, L., Guasch, E., Antoniades, C., Bardinet, I., Benninger, G., Betts, T.R., Brand, E., Breithardt, G., Bucklar-Suchankova, G., Camm, A.J., Cartlidge, D., Casadei, B., Chua, W.W., Crijns, Harry, Deeks, J., Hatem, S., Hidden-Lucet, F., Kääb, S., Maniadakis, N., Martin, S., Mont, L., Reinecke, H., Sinner, M.F., Schotten, Ulrich, Southwood, T., Stoll, Monika, Vardas, P., Wakili, R., West, A., Ziegler, A., Kirchhof, P., RS: CARIM - R2.01 - Clinical atrial fibrillation, Cardiologie, MUMC+: MA Cardiologie (9), RS: CARIM - R2.11 - Experimental atrial fibrillation, Fysiologie, Biochemie, RS: FHML MaCSBio, and RS: CARIM - R1.06 - Genetic Epidemiology and Genomics of cardiovascular diseases
Subjects: CHRONIC KIDNEY-DISEASE, Consensus, LATE GADOLINIUM ENHANCEMENT, Cardiology, LONG-QT SYNDROME, Risk Assessment, EUROPEAN-SOCIETY, RANDOMIZED CLINICAL-TRIAL, CONSENSUS CONFERENCE, LEFT-VENTRICULAR DYSFUNCTION, Treatment Outcome, RISK-FACTOR, Predictive Value of Tests, Risk Factors, Atrial Fibrillation, Preventive Health Services, Animals, Humans, Precision Medicine, PULMONARY VEIN ISOLATION, NERVE-STIMULATION
Abstract: Despite remarkable advances in antiarrhythmic drugs, ablation procedures, and stroke-prevention strategies, atrial fibrillation (AF) remains an important cause of death and disability in middle-aged and elderly individuals. Unstructured management of patients with AF sharply contrasts with our detailed, although incomplete, knowledge of the mechanisms that cause AF and its complications. Altered calcium homeostasis, atrial fibrosis and ageing, ion-channel dysfunction, autonomic imbalance, fat-cell infiltration, and oxidative stress, in addition to a susceptible genetic background, contribute to the promotion, maintenance, and progression of AF. However, clinical management of patients with AF is currently guided by stroke risk parameters, AF pattern, and symptoms. In response to this apparent disconnect between the known pathophysiology of AF and clinical management, we propose a roadmap to develop a set of clinical markers that reflect the major causes of AF in patients. Thereby, the insights into the mechanisms causing AF will be transformed into a format that can underpin future personalized strategies to prevent and treat AF, ultimately informing better patient care.
Published: 2015

41. Calmodulin mutations associated with recurrent cardiac arrest in infants

Author: Crotti, L, Johnson, C, Graf, E, De Ferrari, G, Cuneo, B, Ovadia, M, Papagiannis, J, Feldkamp, M, Rathi, S, Kunic, J, Pedrazzini, M, Wieland, T, Lichtner, P, Beckmann, B, Clark, T, Shaffer, C, Benson, D, Kääb, S, Meitinger, T, Strom, T, Chazin, W, Schwartz, P, George AL, J, Crotti L., Johnson CN., Graf E., De Ferrari G., Cuneo BF., Ovadia M., Papagiannis J., Feldkamp MD., Rathi SG., Kunic JD., Pedrazzini M., Wieland T., Lichtner P., Beckmann BM., Clark T., Shaffer C., Benson DW., Kääb S., Meitinger T., Strom TM., Chazin WJ., Schwartz P, George AL Jr., Crotti, L, Johnson, C, Graf, E, De Ferrari, G, Cuneo, B, Ovadia, M, Papagiannis, J, Feldkamp, M, Rathi, S, Kunic, J, Pedrazzini, M, Wieland, T, Lichtner, P, Beckmann, B, Clark, T, Shaffer, C, Benson, D, Kääb, S, Meitinger, T, Strom, T, Chazin, W, Schwartz, P, George AL, J, Crotti L., Johnson CN., Graf E., De Ferrari G., Cuneo BF., Ovadia M., Papagiannis J., Feldkamp MD., Rathi SG., Kunic JD., Pedrazzini M., Wieland T., Lichtner P., Beckmann BM., Clark T., Shaffer C., Benson DW., Kääb S., Meitinger T., Strom TM., Chazin WJ., Schwartz P, and George AL Jr.
Abstract: Background-: Life-threatening disorders of heart rhythm may arise during infancy and can result in the sudden and tragic death of a child. We performed exome sequencing on 2 unrelated infants presenting with recurrent cardiac arrest to discover a genetic cause. Methods and Results-: We ascertained 2 unrelated infants (probands) with recurrent cardiac arrest and dramatically prolonged QTc interval who were both born to healthy parents. The 2 parent-child trios were investigated with the use of exome sequencing to search for de novo genetic variants. We then performed follow-up candidate gene screening on an independent cohort of 82 subjects with congenital long-QT syndrome without an identified genetic cause. Biochemical studies were performed to determine the functional consequences of mutations discovered in 2 genes encoding calmodulin. We discovered 3 heterozygous de novo mutations in either CALM1 or CALM2, 2 of the 3 human genes encoding calmodulin, in the 2 probands and in 2 additional subjects with recurrent cardiac arrest. All mutation carriers were infants who exhibited life-threatening ventricular arrhythmias combined variably with epilepsy and delayed neurodevelopment. Mutations altered residues in or adjacent to critical calcium binding loops in the calmodulin carboxyl-terminal domain. Recombinant mutant calmodulins exhibited several-fold reductions in calcium binding affinity. Conclusions-: Human calmodulin mutations disrupt calcium ion binding to the protein and are associated with a life-threatening condition in early infancy. Defects in calmodulin function will disrupt important calcium signaling events in heart, affecting membrane ion channels, a plausible molecular mechanism for potentially deadly disturbances in heart rhythm during infancy
Published: 2013

42. Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death

Author: Bezzina, C, Barc, J, Mizusawa, Y, Remme, C, Gourraud, J, Simonet, F, Verkerk, A, Schwartz, P, Crotti, L, Dagradi, F, Guicheney, P, Fressart, V, Leenhardt, A, Antzelevitch, C, Bartkowiak, S, Borggrefe, M, Schimpf, R, Schulze-Bahr, E, Zumhagen, S, Behr, E, Bastiaenen, R, Tfelt-Hansen, J, Olesen, M, Kääb, S, Beckmann, B, Weeke, P, Watanabe, H, Endo, N, Minamino, T, Horie, M, Ohno, S, Hasegawa, K, Makita, N, Nogami, A, Shimizu, W, Aiba, T, Froguel, P, Balkau, B, Lantieri, O, Torchio, M, Wiese, C, Weber, D, Wolswinkel, R, Coronel, R, Boukens, B, Bézieau, S, Charpentier, E, Chatel, S, Despres, A, Gros, F, Kyndt, F, Lecointe, S, Lindenbaum, P, Portero, V, Violleau, J, Gessler, M, Tan, H, Roden, D, Christoffels, V, Le Marec, H, Wilde, A, Probst, V, Schott, J, Dina, C, Redon, R, Bezzina CR., Barc J., Mizusawa Y., Remme CA., Gourraud JB., Simonet F., Verkerk AO., Schwartz PJ., Crotti L., Dagradi F., Guicheney P., Fressart V., Leenhardt A., Antzelevitch C., Bartkowiak S., Borggrefe M., Schimpf R., Schulze-Bahr E., Zumhagen S., Behr ER., Bastiaenen R., Tfelt-Hansen J., Olesen MS., Kääb S., Beckmann BM., Weeke P., Watanabe H., Endo N., Minamino T., Horie M., Ohno S., Hasegawa K., Makita N., Nogami A., Shimizu W., Aiba T., Froguel P., Balkau B., Lantieri O., Torchio M., Wiese C., Weber D., Wolswinkel R., Coronel R., Boukens BJ., Bézieau S., Charpentier E., Chatel S., Despres A., Gros F., Kyndt F., Lecointe S., Lindenbaum P., Portero V., Violleau J., Gessler M., Tan HL., Roden DM., Christoffels VM., Le Marec H., Wilde AA., Probst V., Schott JJ., Dina C., Redon R., Bezzina, C, Barc, J, Mizusawa, Y, Remme, C, Gourraud, J, Simonet, F, Verkerk, A, Schwartz, P, Crotti, L, Dagradi, F, Guicheney, P, Fressart, V, Leenhardt, A, Antzelevitch, C, Bartkowiak, S, Borggrefe, M, Schimpf, R, Schulze-Bahr, E, Zumhagen, S, Behr, E, Bastiaenen, R, Tfelt-Hansen, J, Olesen, M, Kääb, S, Beckmann, B, Weeke, P, Watanabe, H, Endo, N, Minamino, T, Horie, M, Ohno, S, Hasegawa, K, Makita, N, Nogami, A, Shimizu, W, Aiba, T, Froguel, P, Balkau, B, Lantieri, O, Torchio, M, Wiese, C, Weber, D, Wolswinkel, R, Coronel, R, Boukens, B, Bézieau, S, Charpentier, E, Chatel, S, Despres, A, Gros, F, Kyndt, F, Lecointe, S, Lindenbaum, P, Portero, V, Violleau, J, Gessler, M, Tan, H, Roden, D, Christoffels, V, Le Marec, H, Wilde, A, Probst, V, Schott, J, Dina, C, Redon, R, Bezzina CR., Barc J., Mizusawa Y., Remme CA., Gourraud JB., Simonet F., Verkerk AO., Schwartz PJ., Crotti L., Dagradi F., Guicheney P., Fressart V., Leenhardt A., Antzelevitch C., Bartkowiak S., Borggrefe M., Schimpf R., Schulze-Bahr E., Zumhagen S., Behr ER., Bastiaenen R., Tfelt-Hansen J., Olesen MS., Kääb S., Beckmann BM., Weeke P., Watanabe H., Endo N., Minamino T., Horie M., Ohno S., Hasegawa K., Makita N., Nogami A., Shimizu W., Aiba T., Froguel P., Balkau B., Lantieri O., Torchio M., Wiese C., Weber D., Wolswinkel R., Coronel R., Boukens BJ., Bézieau S., Charpentier E., Chatel S., Despres A., Gros F., Kyndt F., Lecointe S., Lindenbaum P., Portero V., Violleau J., Gessler M., Tan HL., Roden DM., Christoffels VM., Le Marec H., Wilde AA., Probst V., Schott JJ., Dina C., and Redon R.
Abstract: Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10 -68; rs9388451, P = 5.1 × 10 -17) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10 -14). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (P trend = 6.1 × 10 -81). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development. Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases
Published: 2013

43. Alteration of Endothelin 1, MCP-1 and Chromogranin A in patients with atrial fibrillation undergoing pulmonary vein isolation

Author: Lackermair, K., primary, Clauss, S., additional, Voigt, T., additional, Klier, I., additional, Summo, C., additional, Hildebrand, B., additional, Nickel, T., additional, Estner, H. L., additional, Kääb, S., additional, Wakili, R., additional, and Wilbert-Lampen, U., additional
Published: 2017
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44. Genotype-phenotype dilemma in a case of sudden cardiac death with the E1053K mutation and a deletion in the SCN5A gene

Author: Jenewein, T., primary, Beckmann, B.M., additional, Rose, S., additional, Osterhues, H.H., additional, Schmidt, U., additional, Wolpert, C., additional, Miny, P., additional, Marschall, C., additional, Alders, M., additional, Bezzina, C.R., additional, Wilde, A.A.M., additional, Kääb, S., additional, and Kauferstein, S., additional
Published: 2017
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45. Kammerflimmern

Author: Gebhardt, C, Angstwurm, M, Steinert, D, Kääb, S, and Schulze-Koops, H
Subjects: ddc: 610, 610 Medical sciences, Medicine
Abstract: Einleitung: Eine 33-jährige Frau wurde bei seit 8/2014 bestehenden rezidivierenden linksthorakalen belastungsunabhängigen Schmerzen mit intermittierenden ST-Hebungen zur Abklärung stationär aufgenommen. Auffällig war laborchemisch neben einem erhöhten Troponin eine[zum vollständigen Text gelangen Sie über die oben angegebene URL], 43. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 25. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)
Published: 2015
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46. Gene-gene Interaction Analyses for Atrial Fibrillation

Author: Lin, H. (Honghuang), Mueller-Nurasyid, M., Smith, A.V. (Albert Vernon), Arking, D.E. (Dan), Barnard, J. (John), Bartz, T.M. (Traci M.), Lunetta, K.L. (Kathryn), Lohman, K. (Kurt), Kleber, M.E. (Marcus), Lubitz, S.A. (Steven), Geelhoed, B. (Bastiaan), Trompet, S. (Stella), Niemeijer, M.N. (Maartje), Kacprowski, T. (Tim), Chasman, D.I. (Daniel), Klarin, D. (Derek), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Meitinger, T. (Thomas), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Soliman, E.Z. (Elsayed Z.), Chen, L. (Lin), Smith, J.D. (Jonathan), Wagoner, D.R. (David) van, Rotter, J.I. (Jerome I.), Psaty, B.M. (Bruce), Xie, Z. (Zhijun), Hendricks, A.E. (Audrey E.), Ding, J. (Jingzhong), Delgado, G.E. (Graciela E.), Verweij, N. (Niek), Harst, P. (Pim) van der, MacFarlane, P.W. (Peter), Ford, I. (Ian), Hofman, A. (Albert), Uitterlinden, A.G. (André), Heeringa, J. (Jan), Franco, O.H. (Oscar), Kors, J.A. (Jan), Weiss, S. (Stefan), Völzke, H. (Henry), Rose, L.M. (Lynda), Natarajan, P. (Pradeep), Kathiresan, S. (Sekar), Kääb, S. (Stefan), Gudnason, V. (Vilmundur), Alonso, A. (Alvaro), Chung, M.K. (Mina), Heckbert, S.R. (Susan), Benjamin, E.J. (Emelia), Liu, Y. (YongMei), März, W. (Winfried), Rienstra, S.A., Jukema, J.W. (Jan Wouter), Stricker, B.H.Ch. (Bruno), Dörr, M. (Marcus), Albert, C.M. (Christine), Ellinor, P.T. (Patrick), Lin, H. (Honghuang), Mueller-Nurasyid, M., Smith, A.V. (Albert Vernon), Arking, D.E. (Dan), Barnard, J. (John), Bartz, T.M. (Traci M.), Lunetta, K.L. (Kathryn), Lohman, K. (Kurt), Kleber, M.E. (Marcus), Lubitz, S.A. (Steven), Geelhoed, B. (Bastiaan), Trompet, S. (Stella), Niemeijer, M.N. (Maartje), Kacprowski, T. (Tim), Chasman, D.I. (Daniel), Klarin, D. (Derek), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Meitinger, T. (Thomas), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Soliman, E.Z. (Elsayed Z.), Chen, L. (Lin), Smith, J.D. (Jonathan), Wagoner, D.R. (David) van, Rotter, J.I. (Jerome I.), Psaty, B.M. (Bruce), Xie, Z. (Zhijun), Hendricks, A.E. (Audrey E.), Ding, J. (Jingzhong), Delgado, G.E. (Graciela E.), Verweij, N. (Niek), Harst, P. (Pim) van der, MacFarlane, P.W. (Peter), Ford, I. (Ian), Hofman, A. (Albert), Uitterlinden, A.G. (André), Heeringa, J. (Jan), Franco, O.H. (Oscar), Kors, J.A. (Jan), Weiss, S. (Stefan), Völzke, H. (Henry), Rose, L.M. (Lynda), Natarajan, P. (Pradeep), Kathiresan, S. (Sekar), Kääb, S. (Stefan), Gudnason, V. (Vilmundur), Alonso, A. (Alvaro), Chung, M.K. (Mina), Heckbert, S.R. (Susan), Benjamin, E.J. (Emelia), Liu, Y. (YongMei), März, W. (Winfried), Rienstra, S.A., Jukema, J.W. (Jan Wouter), Stricker, B.H.Ch. (Bruno), Dörr, M. (Marcus), Albert, C.M. (Christine), and Ellinor, P.T. (Patrick)
Abstract: Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an
Published: 2016
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47. Novel calmodulin (CALM2) mutations associated with congenital arrhythmia susceptibility

Author: Makita, N., Yagihara, N., Crotti, L., Johnson, C.N., Beckmann, B.M., Roh, M.S., Shigemizu, D., Lichtner, P., Ishikawa, T., Aiba, T., Homfray, T., Behr, E.R., Klug, D., Denjoy, I., Mastantuono, E., Theisen, D., Tsunoda, T., Satake, W., Toda, T., Nakagawa, H., Tsuji, Y., Tsuchiya, T., Yamamoto, H., Miyamoto, Y., Endo, N., Kimura, A., Ozaki, K., Motomura, H., Suda, K., Tanaka, T., Schwartz, P.J., Meitinger, T., Kääb, S., Guicheney, P., Shimizu, W., Bhuiyan, Z.A., Watanabe, H., Chazin, W.J., and George, A.L.
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, cardiovascular diseases, Calmodulin, Genetics, Long Qt Syndrome, Ventricular Arrhythmia
Abstract: BACKGROUND: -Genetic predisposition to life-threatening cardiac arrhythmias such as in congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) represent treatable causes of sudden cardiac death in young adults and children. Recently, mutations in calmodulin (CALM1, CALM2) have been associated with severe forms of LQTS and CPVT, with life-threatening arrhythmias occurring very early in life. Additional mutation-positive cases are needed to discern genotype-phenotype correlations associated with calmodulin mutations. METHODS AND RESULTS: -We employed conventional and next-generation sequencing approaches including exome analysis in genotype-negative LQTS probands. We identified five novel de novo missense mutations in CALM2 in three subjects with LQTS (p.N98S, p.N98I, p.D134H) and two subjects with clinical features of both LQTS and CPVT (p.D132E, p.Q136P). Age of onset of major symptoms (syncope or cardiac arrest) ranged from 1-9 years. Three of five probands had cardiac arrest and one of these subjects did not survive. Although all probands had LQTS, two subjects also exhibited electrocardiographic features consistent with CPVT. The clinical severity among subjects in this series was generally less than that originally reported for CALM1 and CALM2 associated with recurrent cardiac arrest during infancy. Four of five probands responded to β-blocker therapy whereas one subject with mutation p.Q136P died suddenly during exertion despite this treatment. Mutations affect conserved residues located within calcium binding loops III (p.N98S, p.N98I) or IV (p.D132E, p.D134H, p.Q136P) and caused reduced calcium binding affinity. CONCLUSIONS: -CALM2M mutations can be associated with LQTS and with overlapping features of LQTS and CPVT.
Published: 2014

48. Integrating genetic, transcriptional, and functional analyses to identify five novel genes for atrial fibrillation

Author: Sinner, M.F., Tucker, N.R., Lunetta, K.L., Ozaki, K., Smith, J.G., Trompet, S., Bis, J.C., Lin, H., Chung, M.K., Nielsen, J.B., Lubitz, S.A., Krijthe, B.P., Magnani, J.W., Ye, J., Gollob, M.H., Tsunoda, T., Müller-Nurasyid, M., Lichtner, P., Peters, A., Dolmatova, E., Kubo, M., Smith, J.D., Psaty, B.M., Smith, N.L., Jukema, J.W., Chasman, D.I., Albert, C.M., Ebana, Y., Furukawa, T., Macfarlane, P.W., Harris, T.B., Darbar, D., Dörr, M., Holst, A.G., Svendsen, J.H., Hofman, A., Uitterlinden, A., Gudnason, V., Isobe, M., Malik, R., Dichgans, M., Rosand, J., van Wagoner, D.R., METASTROKE Consortium (Kääb, S.), AFGen Consortium (Ellinor, P.T.), Benjamin, E.J., Milan, D.J., Melander, O., Heckbert, S.R, Ford, I., Liu, Y., Barnard, J., Olesen, M.S., Stricker, B.H., and Tanaka, T.
Subjects: Genome Wide Association Study, Atrial Fibrillation, Expression Experiments, Genetics, Association Studies, Genetics, Knockout Models, Zebrafish
Abstract: BACKGROUND: -Atrial fibrillation (AF) affects over 30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. METHODS AND RESULTS: -To identify new AF-related genes, we utilized a multifaceted approach, combining large-scale genotyping in two ethnically distinct populations, cis-eQTL mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501, RR=1.18, 95%CI 1.13 - 1.23, p=6.5x10(-16)), GJA1 (rs13216675, RR=1.10, 95%CI 1.06 - 1.14, p=2.2x10(-8)), TBX5 (rs10507248, RR=1.12, 95%CI 1.08 - 1.16, p=5.7x10(-11)), and CAND2 (rs4642101, RR=1.10, 95%CI 1.06 - 1.14, p=9.8x10(-9)). In Japanese, novel loci were identified near NEURL (rs6584555, RR=1.32, 95%CI 1.26-1.39, p=2.0x10(-25)) and CUX2 (rs6490029, RR=1.12, 95%CI 1.08-1.16, p=3.9x10(-9)). The top SNPs or their proxies were identified as cis-eQTLs for the genes CAND2 (p=2.6x10(-19)), GJA1 (p=2.66x10(-6)), and TBX5 (p=1.36x10(-05)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively). CONCLUSIONS: -We have identified five novel loci for AF. Our results further expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation.
Published: 2014

49. Role of common and rare variants in SCN10A: results from the Brugada syndrome QRS locus gene discovery collaborative study

Author: Behr, E, Savio-Galimberti, E, Barc, J, Holst, A, Petropoulou, E, Prins, B, Jabbari, J, Torchio, M, Berthet, M, Mizusawa, Y, Yang, T, Nannenberg, E, Dagradi, F, Weeke, P, Bastiaenan, R, Ackerman, M, Haunso, S, Leenhardt, A, Kääb, S, Probst, V, Redon, R, Sharma, S, Wilde, A, Tfelt-Hansen, J, Schwartz, P, Roden, D, Bezzina, C, Olesen, M, Darbar, D, Guicheney, P, Crotti, L, Jamshidi, Y, Holst, AG, Behr, E, Savio-Galimberti, E, Barc, J, Holst, A, Petropoulou, E, Prins, B, Jabbari, J, Torchio, M, Berthet, M, Mizusawa, Y, Yang, T, Nannenberg, E, Dagradi, F, Weeke, P, Bastiaenan, R, Ackerman, M, Haunso, S, Leenhardt, A, Kääb, S, Probst, V, Redon, R, Sharma, S, Wilde, A, Tfelt-Hansen, J, Schwartz, P, Roden, D, Bezzina, C, Olesen, M, Darbar, D, Guicheney, P, Crotti, L, Jamshidi, Y, and Holst, AG
Abstract: Aims: Brugada syndrome (BrS) remains genetically heterogeneous and is associated with slowed cardiac conduction. We aimed to identify genetic variation in BrS cases at loci associated with QRS duration. Methods and results: A multi-centre study sequenced seven candidate genes (SCN10A, HAND1, PLN, CASQ2, TKT, TBX3, and TBX5) in 156 Caucasian SCN5A mutation-negative BrS patients (80% male; mean age 48) with symptoms (64%) and/or a family history of sudden death (47%) or BrS (18%). Forty-nine variants were identified: 18 were rare (MAF <1%) and non-synonymous; and 11/18 (61.1%), mostly in SCN10A, were predicted as pathogenic using multiple bioinformatics tools. Allele frequencies were compared with the Exome Sequencing and UK10K Projects. SKAT methods tested rare variation in SCN10A finding no statistically significant difference between cases and controls. Co-segregation analysis was possible for four of seven probands carrying a novel pathogenic variant. Only one pedigree (I671V/G1299A in SCN10A) showed co-segregation. The SCN10A SNP V1073 was, however, associated strongly with BrS [66.9 vs. 40.1% (UK10K) OR (95% CI) = 3.02 (2.35-3.87), P = 8.07 × 10-19]. Voltage-clamp experiments for NaV1.8 were performed for SCN10A common variants V1073, A1073, and rare variants of interest: A200V and I671V. V1073, A200V and I671V, demonstrated significant reductions in peak INa compared with ancestral allele A1073 (rs6795970). Conclusion: Rare variants in the screened QRS-associated genes (including SCN10A) are not responsible for a significant proportion of SCN5A mutation negative BrS. The common SNP SCN10A V1073 was strongly associated with BrS and demonstrated loss of NaV1.8 function, as did rare variants in isolated patients.
Published: 2015

50. Opportunities and challenges of current electrophysiology research: A plea to establish 'translational electrophysiology' curricula

Author: Lau, D, Volders, P, Kohl, P, Prinzen, F, Zaza, A, Kääb, S, Oto, A, Schotten, U, Schotten, U., ZAZA, ANTONIO, Lau, D, Volders, P, Kohl, P, Prinzen, F, Zaza, A, Kääb, S, Oto, A, Schotten, U, Schotten, U., and ZAZA, ANTONIO
Abstract: Cardiac electrophysiology has evolved into an important subspecialty in cardiovascular medicine. This is in part due to the significant advances made in our understanding and treatment of heart rhythm disorders following more than a century of scientific discoveries and research. More recently, the rapid development of technology in cellular electrophysiology, molecular biology, genetics, computer modelling, and imaging have led to the exponential growth of knowledge in basic cardiac electrophysiology. The paradigm of evidence-based medicine has led to a more comprehensive decision-making process and most likely to improved outcomes in many patients. However, implementing relevant basic research knowledge in a system of evidence-based medicine appears to be challenging. Furthermore, the current economic climate and the restricted nature of research funding call for improved efficiency of translation from basic discoveries to healthcare delivery. Here, we aim to (i) appraise the broad challenges of translational research in cardiac electrophysiology, (ii) highlight the need for improved strategies in the training of translational electrophysiologists, and (iii) discuss steps towards building a favourable translational research environment and culture.
Published: 2015

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