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1,217 results on '"Kääb Stefan"'

201. Long-Term Clinical Outcome of Cardiogenic Shock Patients Undergoing Impella CP Treatment vs. Standard of Care

Author

Scherer, Clemens, primary, Lüsebrink, Enzo, additional, Kupka, Danny, additional, Stocker, Thomas J., additional, Stark, Konstantin, additional, Stremmel, Christopher, additional, Orban, Mathias, additional, Petzold, Tobias, additional, Germayer, Antonia, additional, Mauthe, Katharina, additional, Kääb, Stefan, additional, Mehilli, Julinda, additional, Braun, Daniel, additional, Theiss, Hans, additional, Brunner, Stefan, additional, Hausleiter, Jörg, additional, Massberg, Steffen, additional, and Orban, Martin, additional

Published
2020
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203. Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation

Author

Reyat, Jasmeet S., primary, Chua, Winnie, additional, Cardoso, Victor R., additional, Witten, Anika, additional, Kastner, Peter M., additional, Kabir, S. Nashitha, additional, Sinner, Moritz F., additional, Wesselink, Robin, additional, Holmes, Andrew P., additional, Pavlovic, Davor, additional, Stoll, Monika, additional, Kääb, Stefan, additional, Gkoutos, Georgios V., additional, de Groot, Joris R., additional, Kirchhof, Paulus, additional, and Fabritz, Larissa, additional

Published
2020
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204. Subcutaneous or Transvenous Defibrillator Therapy

Author

Knops, Reinoud E., primary, Olde Nordkamp, Louise R.A., additional, Delnoy, Peter-Paul H.M., additional, Boersma, Lucas V.A., additional, Kuschyk, Jürgen, additional, El-Chami, Mikhael F., additional, Bonnemeier, Hendrik, additional, Behr, Elijah R., additional, Brouwer, Tom F., additional, Kääb, Stefan, additional, Mittal, Suneet, additional, Quast, Anne-Floor B.E., additional, Smeding, Lonneke, additional, van der Stuijt, Willeke, additional, de Weger, Anouk, additional, de Wilde, Koen C., additional, Bijsterveld, Nick R., additional, Richter, Sergio, additional, Brouwer, Marc A., additional, de Groot, Joris R., additional, Kooiman, Kirsten M., additional, Lambiase, Pier D., additional, Neuzil, Petr, additional, Vernooy, Kevin, additional, Alings, Marco, additional, Betts, Tim R., additional, Bracke, Frank A.L.E., additional, Burke, Martin C., additional, de Jong, Jonas S.S.G., additional, Wright, David J., additional, Tijssen, Jan G.P., additional, and Wilde, Arthur A.M., additional

Published
2020
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205. Rhythmusmonitoring

Author

von Falkenhausen, Aenne S., primary, Fichtner, Stephanie, additional, Kääb, Stefan, additional, and Sinner, Moritz F., additional

Published
2020
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209. The INFluence of Remote monitoring on Anxiety/depRession, quality of lifE, and Device acceptance in ICD patients: a prospective, randomized, controlled, single-center trial

Author

Leppert, Florian, primary, Siebermair, Johannes, additional, Wesemann, Ulrich, additional, Martens, Eimo, additional, Sattler, Stefan M., additional, Scholz, Stefan, additional, Veith, Stefan, additional, Greiner, Wolfgang, additional, Rassaf, Tienush, additional, Kääb, Stefan, additional, and Wakili, Reza, additional

Published
2020
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210. Characterization of a porcine model of atrial arrhythmogenicity in the context of ischaemic heart failure

Author

Clauss, Sebastian, primary, Schüttler, Dominik, additional, Bleyer, Christina, additional, Vlcek, Julia, additional, Shakarami, Mehdi, additional, Tomsits, Philipp, additional, Schneider, Sarah, additional, Maderspacher, Florian, additional, Chataut, Kavi, additional, Trebo, Anna, additional, Wang, Christine, additional, Kleeberger, Jan, additional, Xia, Ruibing, additional, Baloch, Elisabeth, additional, Hildebrand, Bianca, additional, Massberg, Steffen, additional, Wakili, Reza, additional, and Kääb, Stefan, additional

Published
2020
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211. Update on Weaning from Veno-Arterial Extracorporeal Membrane Oxygenation

Author

Lüsebrink, Enzo, primary, Stremmel, Christopher, additional, Stark, Konstantin, additional, Joskowiak, Dominik, additional, Czermak, Thomas, additional, Born, Frank, additional, Kupka, Danny, additional, Scherer, Clemens, additional, Orban, Mathias, additional, Petzold, Tobias, additional, von Samson-Himmelstjerna, Patrick, additional, Kääb, Stefan, additional, Hagl, Christian, additional, Massberg, Steffen, additional, Peterss, Sven, additional, and Orban, Martin, additional

Published
2020
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212. Genome-wide association analysis identifies multiple loci related to resting heart rate

Author

Eijgelsheim, Mark, Newton-Cheh, Christopher, Sotoodehnia, Nona, de Bakker, Paul I.W., Müller, Martina, Morrison, Alanna C., Smith, Albert V., Isaacs, Aaron, Sanna, Serena, Dörr, Marcus, Navarro, Pau, Fuchsberger, Christian, Nolte, Ilja M., de Geus, Eco J.C., Estrada, Karol, Hwang, Shih-Jen, Bis, Joshua C., Rückert, Ina-Maria, Alonso, Alvaro, Launer, Lenore J., Hottenga, Jouke Jan, Rivadeneira, Fernando, Noseworthy, Peter A., Rice, Kenneth M., Perz, Siegfried, Arking, Dan E., Spector, Tim D., Kors, Jan A., Aulchenko, Yurii S., Tarasov, Kirill V., Homuth, Georg, Wild, Sarah H., Marroni, Fabio, Gieger, Christian, Licht, Carmilla M., Prineas, Ronald J., Hofman, Albert, Rotter, Jerome I., Hicks, Andrew A., Ernst, Florian, Najjar, Samer S., Wright, Alan F., Peters, Annette, Fox, Ervin R., Oostra, Ben A., Kroemer, Heyo K., Couper, David, Völzke, Henry, Campbell, Harry, Meitinger, Thomas, Uda, Manuela, Witteman, Jacqueline C.M., Psaty, Bruce M., Wichmann, H-Erich, Harris, Tamara B., Kääb, Stefan, Siscovick, David S., Jamshidi, Yalda, Uitterlinden, André G., Folsom, Aaron R., Larson, Martin G., Wilson, James F., Penninx, Brenda W., Snieder, Harold, Pramstaller, Peter P., van Duijn, Cornelia M., Lakatta, Edward G., Felix, Stephan B., Gudnason, Vilmundur, Pfeufer, Arne, Heckbert, Susan R., Stricker, Bruno H.Ch., Boerwinkle, Eric, and OʼDonnell, Christopher J.

Published
2010
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215. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation

Author

Kääb, Stefan, Darbar, Dawood, van Noord, Charlotte, Dupuis, Josée, Pfeufer, Arne, Newton-Cheh, Christopher, Schnabel, Renate, Makino, Seiko, Sinner, Moritz F., Kannankeril, Prince J., Beckmann, Britt M., Choudry, Subbarao, Donahue, Brian S., Heeringa, Jan, Perz, Siegfried, Lunetta, Kathryn L., Larson, Martin G., Levy, Daniel, MacRae, Calum A., Ruskin, Jeremy N., Wacker, Annette, Schömig, Albert, Wichmann, H-Erich, Steinbeck, Gerhard, Meitinger, Thomas, Uitterlinden, André G., Witteman, Jacqueline C.M., Roden, Dan M., Benjamin, Emelia J., and Ellinor, Patrick T.

Published
2009

217. Chronically elevated branched chain amino acid levels are pro-arrhythmic.

Author

Portero, Vincent, Nicol, Thomas, Podliesna, Svitlana, Marchal, Gerard A, Baartscheer, Antonius, Casini, Simona, Tadros, Rafik, Treur, Jorien L, Tanck, Michael W T, Cox, I Jane, Probert, Fay, Hough, Tertius A, Falcone, Sara, Beekman, Leander, Müller-Nurasyid, Martina, Kastenmüller, Gabi, Gieger, Christian, Peters, Annette, Kääb, Stefan, and Sinner, Moritz F

Subjects
BRANCHED chain amino acids, AMINOTRANSFERASES, CARDIAC arrest, HEART failure, SUDDEN death, ARRHYTHMIA, NONSENSE mutation
Abstract

Aims Cardiac arrhythmias comprise a major health and economic burden and are associated with significant morbidity and mortality, including cardiac failure, stroke, and sudden cardiac death (SCD). Development of efficient preventive and therapeutic strategies is hampered by incomplete knowledge of disease mechanisms and pathways. Our aim is to identify novel mechanisms underlying cardiac arrhythmia and SCD using an unbiased approach. Methods and results We employed a phenotype-driven N -ethyl- N -nitrosourea mutagenesis screen and identified a mouse line with a high incidence of sudden death at young age (6–9 weeks) in the absence of prior symptoms. Affected mice were found to be homozygous for the nonsense mutation Bcat2 p.Q300*/p.Q300* in the Bcat2 gene encoding branched chain amino acid transaminase 2. At the age of 4–5 weeks, Bcat2 p.Q300*/p.Q300* mice displayed drastic increase of plasma levels of branch chain amino acids (BCAAs—leucine, isoleucine, valine) due to the incomplete catabolism of BCAAs, in addition to inducible arrhythmias ex vivo as well as cardiac conduction and repolarization disturbances. In line with these findings, plasma BCAA levels were positively correlated to electrocardiogram indices of conduction and repolarization in the German community-based KORA F4 Study. Isolated cardiomyocytes from Bcat2 p.Q300*/p.Q300* mice revealed action potential (AP) prolongation, pro-arrhythmic events (early and late afterdepolarizations, triggered APs), and dysregulated calcium homeostasis. Incubation of human pluripotent stem cell-derived cardiomyocytes with elevated concentration of BCAAs induced similar calcium dysregulation and pro-arrhythmic events which were prevented by rapamycin, demonstrating the crucial involvement of mTOR pathway activation. Conclusions Our findings identify for the first time a causative link between elevated BCAAs and arrhythmia, which has implications for arrhythmogenesis in conditions associated with BCAA metabolism dysregulation such as diabetes, metabolic syndrome, and heart failure. [ABSTRACT FROM AUTHOR]

Published
2022
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219. Assessment of right ventricular sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy : An ¹²³I-metaiodobenzylguanidine SPECT/CT study

Author

Todica, Andrei, Siebermair, Johannes, Schiller, Julia, Zacherl, Mathias J., Fendler, Wolfgang P., Massberg, Steffen, Bartenstein, Peter, Cyran, Clemens C., Kääb, Stefan, Hacker, Marcus, Wakili, Reza, and Lehner, Sebastian

Subjects
Medizin
Abstract

Purpose: The purpose of the study was to evaluate a novel approach for the quantification of right ventricular sympathetic dysfunction in patients diagnosed with ARVC/D through state-of-the-art functional SPECT/CT hybrid imaging. Methods: Sympathetic innervation of the heart was assessed using 123I-MIBG-SPECT/CT in 17 patients diagnosed with ARVC according to the modified task force criteria, and in 10 patients diagnosed with idiopathic ventricular fibrillation (IVF). The 123I-MIBG-uptake in the left (LV) and right ventricle (RV) was evaluated separately based on anatomic information derived from the CT scan, and compared to the uptake in the mediastinum (M). Results: There was a significant difference in the LV/M ratio between the ARVC/D and the IVF groups (3.2 ± 0.5 vs. 3.9 ± 0.8, P = 0.014), with a cut-off value of 3.41 (77% sensitivity, 80% specificity, AUC 0.78). There was a highly significant difference in the mean RV/M ratios between both groups (1.6 ± 0.3 vs. 2.0 ± 0.2, P = 0.001), with optimal cut-off for discrimination at 1.86 (88% sensitivity, 90% specificity, AUC 0.93). Conclusion: Employing state-of-the-art functional SPECT/CT hybrid imaging, we could reliably assess and quantify right and left ventricular sympathetic innervation. The RV/M ratio was significantly lower in patients diagnosed with ARVC/D and provided sensitive and specific discrimination between patients with ARVC/D and IVF patients.

Published
2020

220. Appropriate Shocks and Mortality in Patients With Versus Without Diabetes With Prophylactic Implantable Cardioverter Defibrillators

Author

Junttila, M. Juhani, Pelli, Ari, Kenttä, Tuomas V., Friede, Tim, Willems, Rik, Bergau, Leonard, Malik, Marek, Vandenberk, Bert, Vos, Marc A., Schmidt, Georg, Merkely, Bela, Lubinski, Andrzej, Svetlosak, Martin, Braunschweig, Frieder, Harden, Markus, Zabel, Markus, Huikuri, Heikki V., Sticherling, Christian, Seegers, Joachim, Hasenfuß, Gerd, Munoz-Exposito, Pascal, Tichelbäcker, Tobias, Kirova, Aleksandra, Schlögl, Simon, Sritharan, Rajevaa, Jörß, Katharina, Macken, Jessica, Misdaq, Misbah, Rudolph, Kornelia, Bauer, Axel, Meyer-Zürn, Christine, Eick, Christian, rechts der Isar, Klinikum, Schmidt, Goerg, Müller, Alexander, Dommasch, Michael, Sinnecker, Daniel, Kääb, Stefan, Sinner, Moritz F., Dissmann, Rüdiger, Burmester, Ute, Behrens, Steffen, Gregor, Martina, Stefanow, Stefan, Rüb, Norman, Wolpert, Christian, Bimmel, Dieter, Lieberz, Christiane, Maier, Lars S., Schwinger, Robert H.G., Blaschke, Florian, Pieske, Burkert, Grönefeld, Gerian, Klein, Gunnar, Gardiwal, Ajmal, Szeplaki, Gabor, Perge, Peter, Szavits Nossan, Janko, Rotkvić, Luka, Pavlovic, Nikola, Manola, Sime, Vinter, Ozren, Benko, Ivica, Brusic, Sandro, Avdovic, Ervin, Klasan, Marina, Bakotic, Zoran, Anic, Ante, Jurisic, Zrinka, Kowalczyk, Emilia, Kucejko, Tomasz, Czechowska, Agnieszka, Wybor, Katarina, Cygankiewicz, Iwona, Ptaszyński, Pawel, Kasprzak, Jaroslaw, Qavoq, Dariusz, Guzik, Przemyslaw, Krauze, Tomasz, Sterlinski, Maciej, Hatala, Robert, Kaliska, Gabriela, Martinek, Jozef, Hastrup Svendsen, Jesper, Thamsborg, Karen, Hansen, Jim, Schloett-Hyldelund, Ida-Maria, Laage-Petersen, Julie, van Soest, Sofie, Flevari, Panayota, Katsaras, Dimitrios, Katsimardos, Andreas, Leftheriotis, Dionyssios, Papangelopoulou, Konstantinia, Varlamos, Charalambos, Traykov, Vassil, Velchev, Vasil, Iovev, Svetoslav, Shalganov, Tchavdar, Conen, David, Giesebart, Sarah, Novotny, Tomas, Kozak, Milan, Taborsky, Milos, Galuszka, Jan, Tuinenburg, Anton E., Wijers, Sofieke, Dunnink, Albert, Sprenkeler, David, Brugada, Josep, Arbelo, Elena, Trucco, Emilce, Vidorreta, Silvia, Kenttä, Tuomas, Huikuri, Pirkko, Koski, Päivi, Karlsson, Helena, Ersgaard, David, Platonov, Pyotr, Klingenheben, Thomas, and EU-CERT-ICD Investigators

Subjects
Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Ventricular Function, Left, DISEASE, Sudden cardiac death, Endocrinology, 0302 clinical medicine, Tachycardia, Medicine, FIBROSIS, Advanced and Specialised Nursing, 030212 general & internal medicine, Registries, 11 Medical and Health Sciences, RISK, Electroshock, OUTCOMES, Incidence (epidemiology), Incidence, Hazard ratio, ASSOCIATION, Middle Aged, Implantable cardioverter-defibrillator, 3. Good health, Defibrillators, Implantable, Diabetes and Metabolism, Primary Prevention, PRESERVED EJECTION FRACTION, Cardiology, Female, VENTRICULAR-FIBRILLATION, Life Sciences & Biomedicine, medicine.medical_specialty, 030209 endocrinology & metabolism, Lower risk, Sudden death, 03 medical and health sciences, Endocrinology & Metabolism, Diabetes mellitus, Internal medicine, Journal Article, Internal Medicine, Diabetes Mellitus, Humans, Aged, Retrospective Studies, Advanced and Specialized Nursing, Science & Technology, business.industry, Retrospective cohort study, medicine.disease, Death, Sudden, Cardiac, MYOCARDIAL-INFARCTION, ICD sudden death cardiomyopathy, business, SUDDEN CARDIAC DEATH, Diabetic Angiopathies, Follow-Up Studies
Abstract

OBJECTIVE Diabetes increases the risk of all-cause mortality and sudden cardiac death (SCD). The exact mechanisms leading to sudden death in diabetes are not well known. We compared the incidence of appropriate shocks and mortality in patients with versus without diabetes with a prophylactic implantable cardioverter defibrillator (ICD) included in the retrospective EU-CERT-ICD registry. RESEARCH DESIGN AND METHODS AND RESULTS A total of 3,535 patients from 12 European EU-CERT-ICD centers with a mean age of 63.7 ± 11.2 years (82% males) at the time of ICD implantation were included in the analysis. A total of 995 patients (28%) had a history of diabetes. All patients had an ICD implanted for primary SCD prevention. End points were appropriate shock and all-cause mortality. Mean follow-up time was 3.2 ± 2.3 years. Diabetes was associated with a lower risk of appropriate shocks (adjusted hazard ratio [HR] 0.77 [95% CI 0.62–0.96], P = 0.02). However, patients with diabetes had significantly higher mortality (adjusted HR 1.30 [95% CI 1.11–1.53], P = 0.001). CONCLUSIONS All-cause mortality is higher in patients with diabetes than in patients without diabetes with primary prophylactic ICDs. Subsequently, patients with diabetes have a lower incidence of appropriate ICD shocks, indicating that the excess mortality might not be caused primarily by ventricular tachyarrhythmias. These findings suggest a limitation of the potential of prophylactic ICD therapy to improve survival in patients with diabetes with impaired left ventricular function.

Published
2020

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

Author

Berndt, Markus, Thomas, Franziska, Bauer, Daniel, Härtl, Anja, Hege, Inga, Kääb, Stefan, Fischer, Martin R., and Heitzmann, Nicole

Subjects
Adult, Male, Students, Medical, 020205 medical informatics, computergestütztes Lernen, prompts, computer-supported learning, lcsh:Medicine, 610 Medicine & health, ECG interpretation, 02 engineering and technology, Article, Electrocardiography, error analysis prompts, Begründungsprompts, Surveys and Questionnaires, 0202 electrical engineering, electronic engineering, information engineering, Fehleranalyseprompts, Humans, Learning, EKG, lcsh:LC8-6691, Motivation, lcsh:Special aspects of education, ECG, lcsh:R, 05 social sciences, 050301 education, 610 Medical sciences, Medicine, ddc: 610, justification prompts, Female, Clinical Competence, 0503 education, EKG-Befundung, Education, Medical, Undergraduate
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 η2=.10; and a negative effect on student motivation, F(1,96)=8.13 , p=.005, partial η2=.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 η2=.10, und negativ auf die Motivation der Studierenden, F(1,96)=8.13, p=.005, partielles η2=.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., GMS Journal for Medical Education; 37(1):Doc11

Published
2020
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229. Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation

Author

Weng, Lu Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J., Haessler, Jeffrey, Bihlmeyer, Nathan A., Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A., Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E., van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R., Padmanabhan, Sandosh, Kors, Jan A., de Boer, Rudolf A., van der Meer, Peter, Sinner, Moritz F., Waldenberger, Melanie, Psaty, Bruce M., Taylor, Kent D., Völker, Uwe, Kanters, Jørgen K., Li, Man, Alonso, Alvaro, Perez, Marco V., Vaartjes, Ilonca, Bots, Michiel L., Huang, Paul L., Heckbert, Susan R., Lin, Henry J., Kornej, Jelena, Munroe, Patricia B., van Duijn, Cornelia M., Asselbergs, Folkert W., Stricker, Bruno H., van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I., Mook-Kanamori, Dennis O., Dörr, Marcus, Felix, Stephan B., Linneberg, Allan, Hansen, Torben, Arking, Dan E., Kooperberg, Charles, Benjamin, Emelia J., Lunetta, Kathryn L., Ellinor, Patrick T., Lubitz, Steven A., Weng, Lu Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J., Haessler, Jeffrey, Bihlmeyer, Nathan A., Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A., Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E., van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R., Padmanabhan, Sandosh, Kors, Jan A., de Boer, Rudolf A., van der Meer, Peter, Sinner, Moritz F., Waldenberger, Melanie, Psaty, Bruce M., Taylor, Kent D., Völker, Uwe, Kanters, Jørgen K., Li, Man, Alonso, Alvaro, Perez, Marco V., Vaartjes, Ilonca, Bots, Michiel L., Huang, Paul L., Heckbert, Susan R., Lin, Henry J., Kornej, Jelena, Munroe, Patricia B., van Duijn, Cornelia M., Asselbergs, Folkert W., Stricker, Bruno H., van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I., Mook-Kanamori, Dennis O., Dörr, Marcus, Felix, Stephan B., Linneberg, Allan, Hansen, Torben, Arking, Dan E., Kooperberg, Charles, Benjamin, Emelia J., Lunetta, Kathryn L., Ellinor, Patrick T., and Lubitz, Steven A.

Abstract

BACKGROUND: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. METHODS: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. RESULTS: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. CONCLUSIONS: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.

Published
2020

230. Continued misuse of orphan drug legislation:a life-threatening risk for mexiletine

Author

Postema, Pieter G, Schwartz, Peter J, Arbelo, Elena, Bannenberg, Wilbert J, Behr, Elijah R, Belhassen, Bernard, Brugada, Josep, Brugada, Pedro, John Camm, A, Casado-Arroyo, Ruben, 't Hoen, Ellen, Hollak, Carla E M, Kääb, Stefan, Lambiase, Pier D, Leenhardt, Antoine, Priori, Silvia G, Probst, Vincent, Stunnenberg, Bas C, Tfelt-Hansen, Jacob, Van Engelen, Baziel G M, Veltmann, Christian, Viskin, Sami, Wilde, Arthur A M, Postema, Pieter G, Schwartz, Peter J, Arbelo, Elena, Bannenberg, Wilbert J, Behr, Elijah R, Belhassen, Bernard, Brugada, Josep, Brugada, Pedro, John Camm, A, Casado-Arroyo, Ruben, 't Hoen, Ellen, Hollak, Carla E M, Kääb, Stefan, Lambiase, Pier D, Leenhardt, Antoine, Priori, Silvia G, Probst, Vincent, Stunnenberg, Bas C, Tfelt-Hansen, Jacob, Van Engelen, Baziel G M, Veltmann, Christian, Viskin, Sami, and Wilde, Arthur A M

Published
2020

231. Genetic determinants of electrocardiographic P-wave duration and relation to atrial fibrillation

Author

Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, RF&S Team 1 Medisch, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Team Medisch, AIOS Anesthesiologie, Weng, Lu Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J., Haessler, Jeffrey, Bihlmeyer, Nathan A., Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A., Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E., van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R., Padmanabhan, Sandosh, Kors, Jan A., de Boer, Rudolf A., van der Meer, Peter, Sinner, Moritz F., Waldenberger, Melanie, Psaty, Bruce M., Taylor, Kent D., Völker, Uwe, Kanters, Jørgen K., Li, Man, Alonso, Alvaro, Perez, Marco V., Vaartjes, Ilonca, Bots, Michiel L., Huang, Paul L., Heckbert, Susan R., Lin, Henry J., Kornej, Jelena, Munroe, Patricia B., van Duijn, Cornelia M., Asselbergs, Folkert W., Stricker, Bruno H., van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I., Mook-Kanamori, Dennis O., Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, RF&S Team 1 Medisch, Cardiovasculaire Epi Team 5, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Team Medisch, AIOS Anesthesiologie, Weng, Lu Chen, Hall, Amelia Weber, Choi, Seung Hoan, Jurgens, Sean J., Haessler, Jeffrey, Bihlmeyer, Nathan A., Grarup, Niels, Lin, Honghuang, Teumer, Alexander, Li-Gao, Ruifang, Yao, Jie, Guo, Xiuqing, Brody, Jennifer A., Müller-Nurasyid, Martina, Schramm, Katharina, Verweij, Niek, van den Berg, Marten E., van Setten, Jessica, Isaacs, Aaron, Ramírez, Julia, Warren, Helen R., Padmanabhan, Sandosh, Kors, Jan A., de Boer, Rudolf A., van der Meer, Peter, Sinner, Moritz F., Waldenberger, Melanie, Psaty, Bruce M., Taylor, Kent D., Völker, Uwe, Kanters, Jørgen K., Li, Man, Alonso, Alvaro, Perez, Marco V., Vaartjes, Ilonca, Bots, Michiel L., Huang, Paul L., Heckbert, Susan R., Lin, Henry J., Kornej, Jelena, Munroe, Patricia B., van Duijn, Cornelia M., Asselbergs, Folkert W., Stricker, Bruno H., van der Harst, Pim, Kääb, Stefan, Peters, Annette, Sotoodehnia, Nona, Rotter, Jerome I., and Mook-Kanamori, Dennis O.

Published
2020

232. Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome

Author

ZL Neuromusculaire Ziekten Medisch, Brain, Projectafdeling ALS, Regenerative Medicine and Stem Cells, Circulatory Health, Genetica, UMC Utrecht, Lahrouchi, Najim, Tadros, Rafik, Crotti, Lia, Mizusawa, Yuka, Postema, Pieter G, Beekman, Leander, Walsh, Roddy, Hasegawa, Kanae, Barc, Julien, Ernsting, Marko, Turkowski, Kari L, Mazzanti, Andrea, Beckmann, Britt M, Shimamoto, Keiko, Diamant, Ulla-Britt, Wijeyeratne, Yanushi D, Kucho, Yu, Robyns, Tomas, Ishikawa, Taisuke, Arbelo, Elena, Christiansen, Michael, Winbo, Annika, Jabbari, Reza, Lubitz, Steven A, Steinfurt, Johannes, Rudic, Boris, Loeys, Bart, Shoemaker, M Ben, Weeke, Peter E, Pfeiffer, Ryan, Davies, Brianna, Andorin, Antoine, Hofman, Nynke, Dagradi, Federica, Pedrazzini, Matteo, Tester, David J, Bos, J Martijn, Sarquella-Brugada, Georgia, Campuzano, Óscar, Platonov, Pyotr G, Stallmeyer, Birgit, Zumhagen, Sven, Nannenberg, Eline A, Veldink, Jan H, van den Berg, Leonard H, Al-Chalabi, Ammar, Shaw, Christopher E, Shaw, Pamela J, Morrison, Karen E, Andersen, Peter M, Müller-Nurasyid, Martina, Cusi, Daniele, Barlassina, Cristina, Galan, Pilar, Lathrop, Mark, Munter, Markus, Werge, Thomas, Ribasés, Marta, Aung, Tin, Khor, Chiea C, Ozaki, Mineo, Lichtner, Peter, Meitinger, Thomas, van Tintelen, J Peter, Hoedemaekers, Yvonne, Denjoy, Isabelle, Leenhardt, Antoine, Napolitano, Carlo, Shimizu, Wataru, Schott, Jean-Jacques, Gourraud, Jean-Baptiste, Makiyama, Takeru, Ohno, Seiko, Itoh, Hideki, Krahn, Andrew D, Antzelevitch, Charles, Roden, Dan M, Saenen, Johan, Borggrefe, Martin, Odening, Katja E, Ellinor, Patrick T, Tfelt-Hansen, Jacob, Skinner, Jonathan R, van den Berg, Maarten P, Olesen, Morten Salling, Brugada, Josep, Brugada, Ramón, Makita, Naomasa, Breckpot, Jeroen, Yoshinaga, Masao, Behr, Elijah R, Rydberg, Annika, Aiba, Takeshi, Kääb, Stefan, Priori, Silvia G, Guicheney, Pascale, Tan, Hanno L, Newton-Cheh, Christopher, Ackerman, Michael J, Schwartz, Peter J, Schulze-Bahr, Eric, Probst, Vincent, Horie, Minoru, Wilde, Arthur A, Tanck, Michael W T, Bezzina, Connie R, ZL Neuromusculaire Ziekten Medisch, Brain, Projectafdeling ALS, Regenerative Medicine and Stem Cells, Circulatory Health, Genetica, UMC Utrecht, Lahrouchi, Najim, Tadros, Rafik, Crotti, Lia, Mizusawa, Yuka, Postema, Pieter G, Beekman, Leander, Walsh, Roddy, Hasegawa, Kanae, Barc, Julien, Ernsting, Marko, Turkowski, Kari L, Mazzanti, Andrea, Beckmann, Britt M, Shimamoto, Keiko, Diamant, Ulla-Britt, Wijeyeratne, Yanushi D, Kucho, Yu, Robyns, Tomas, Ishikawa, Taisuke, Arbelo, Elena, Christiansen, Michael, Winbo, Annika, Jabbari, Reza, Lubitz, Steven A, Steinfurt, Johannes, Rudic, Boris, Loeys, Bart, Shoemaker, M Ben, Weeke, Peter E, Pfeiffer, Ryan, Davies, Brianna, Andorin, Antoine, Hofman, Nynke, Dagradi, Federica, Pedrazzini, Matteo, Tester, David J, Bos, J Martijn, Sarquella-Brugada, Georgia, Campuzano, Óscar, Platonov, Pyotr G, Stallmeyer, Birgit, Zumhagen, Sven, Nannenberg, Eline A, Veldink, Jan H, van den Berg, Leonard H, Al-Chalabi, Ammar, Shaw, Christopher E, Shaw, Pamela J, Morrison, Karen E, Andersen, Peter M, Müller-Nurasyid, Martina, Cusi, Daniele, Barlassina, Cristina, Galan, Pilar, Lathrop, Mark, Munter, Markus, Werge, Thomas, Ribasés, Marta, Aung, Tin, Khor, Chiea C, Ozaki, Mineo, Lichtner, Peter, Meitinger, Thomas, van Tintelen, J Peter, Hoedemaekers, Yvonne, Denjoy, Isabelle, Leenhardt, Antoine, Napolitano, Carlo, Shimizu, Wataru, Schott, Jean-Jacques, Gourraud, Jean-Baptiste, Makiyama, Takeru, Ohno, Seiko, Itoh, Hideki, Krahn, Andrew D, Antzelevitch, Charles, Roden, Dan M, Saenen, Johan, Borggrefe, Martin, Odening, Katja E, Ellinor, Patrick T, Tfelt-Hansen, Jacob, Skinner, Jonathan R, van den Berg, Maarten P, Olesen, Morten Salling, Brugada, Josep, Brugada, Ramón, Makita, Naomasa, Breckpot, Jeroen, Yoshinaga, Masao, Behr, Elijah R, Rydberg, Annika, Aiba, Takeshi, Kääb, Stefan, Priori, Silvia G, Guicheney, Pascale, Tan, Hanno L, Newton-Cheh, Christopher, Ackerman, Michael J, Schwartz, Peter J, Schulze-Bahr, Eric, Probst, Vincent, Horie, Minoru, Wilde, Arthur A, Tanck, Michael W T, and Bezzina, Connie R

Published
2020

234. Genomic risk scores, biomolecules, and clinical conditions to predict atrial fibrillation: time to integrate what we can measure.

Author

Kääb, Stefan, Holm, Hilma, and Kirchhof, Paulus

Subjects
ATRIAL fibrillation, DISEASE risk factors, ATRIAL flutter, BIOMOLECULES
Abstract

The irregular pulse that we now call atrial fibrillation (AF) was first described in 1628 by William Harvey in his I Exercitatio de Motu Cordis i .[1] A few centuries later, Einthoven first recorded AF on the electrocardiogram. Therefore, accounting for clinical risk factors is not expected to affect its association with AF and hence its predictive value.[4] The study participants had established cardiovascular conditions and were therefore at higher risk of incident AF, reflected in a relatively high 3-year incidence rate of AF of 3.6%. P.K. is listed as inventor on two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). [Extracted from the article]

Published
2023
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236. Inappropriate Therapy and Shock Rates Between the Subcutaneous and Transvenous Implantable Cardiac Defibrillator: A Secondary Analysis of the PRAETORIAN Trial

Author

Olde Nordkamp, Louise R.A., Pepplinkhuizen, Shari, Ghani, Abdul, Boersma, Lucas V.A., Kuschyk, Juergen, El-Chami, Mikhael F., Behr, Elijah R., Brouwer, Tom F., Kääb, Stefan, Mittal, Suneet, Quast, Anne-Floor B.E., van der Stuijt, Willeke, Smeding, Lonneke, de Veld, Jolien A., Tijssen, Jan G.P., Bijsterveld, Nick R., Richter, Sergio, Brouwer, Marc A., de Groot, Joris R., Kooiman, Kirsten M., Lambiase, Pier D., Neuzil, Petr, Vernooy, Kevin, Alings, Marco, Betts, Timothy R., Bracke, Frank A.L.E., Burke, Martin C., de Jong, Jonas S.S.G., Wright, David J., Jansen, Ward P.J., Whinnett, Zachary I., Nordbeck, Peter, Knaut, Michael, Philbert, Berit T., van Opstal, Jurren M., Chicos, Alexandru B., Allaart, Cornelis P., Borger van der Burg, Alida E., Dizon, Jose M., Miller, Marc A., Nemirovsky, Dmitry, Surber, Ralf, Upadhyay, Gaurav A., Weiss, Raul, de Weger, Anouk, Wilde, Arthur A.M., and Knops, Reinoud E.

Published
2024
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237. Procoagulant platelet sentinels prevent inflammatory bleeding through GPIIBIIIA and GPVI

Author

Kaiser, Rainer, Escaig, Raphael, Kranich, Jan, Hoffknecht, Marie-Louise, Anjum, Afra, Polewka, Vivien, Mader, Magdalena, Hu, Wenbo, Belz, Larissa, Gold, Christoph, Titova, Anna, Lorenz, Michael, Pekayvaz, Kami, Kääb, Stefan, Gaertner, Florian, Stark, Konstantin, Brocker, Thomas, Massberg, Steffen, and Nicolai, Leo

Abstract

Impairment of vascular integrity is a hallmark of inflammatory diseases. We recently reported that single immune-responsive platelets migrate and reposition themselves to sites of vascular injury to prevent bleeding. However, it remains unclear how single platelets preserve vascular integrity once encountering endothelial breaches. Here we demonstrate by intravital microscopy combined with genetic mouse models that procoagulant activation (PA) of single platelets and subsequent recruitment of the coagulation cascade are crucial for the prevention of inflammatory bleeding. Using a novel lactadherin-based compound, we detect phosphatidylserine (PS)-positive procoagulant platelets in the inflamed vasculature. We identify exposed collagen as the central trigger arresting platelets and initiating subsequent PA in a CypD- and TMEM16F-dependent manner both in vivo and in vitro. Platelet PA promotes binding of the prothrombinase complex to the platelet membrane, greatly enhancing thrombin activity and resulting in fibrin formation. PA of migrating platelets is initiated by costimulation via integrin αIIbβ3 (GPIIBIIIA)/Gα13-mediated outside-in signaling and glycoprotein VI signaling, leading to an above-threshold intracellular calcium release. This effectively targets the coagulation cascade to breaches of vascular integrity identified by patrolling platelets. Platelet-specific genetic loss of either CypD or TMEM16F as well as combined blockade of platelet GPIIBIIIA and glycoprotein VI reduce platelet PA in vivo and aggravate pulmonary inflammatory hemorrhage. Our findings illustrate a novel role of procoagulant platelets in the prevention of inflammatory bleeding and provide evidence that PA of patrolling platelet sentinels effectively targets and confines activation of coagulation to breaches of vascular integrity.

Published
2022
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238. Preventive or Deferred Ablation of Ventricular Tachycardia in Patients With Ischemic Cardiomyopathy and Implantable Defibrillator (BERLIN VT)

Author

Willems, Stephan, primary, Tilz, Roland Richard, additional, Steven, Daniel, additional, Kääb, Stefan, additional, Wegscheider, Karl, additional, Gellér, László, additional, Meyer, Christian, additional, Heeger, Christian-Hendrik, additional, Metzner, Andreas, additional, Sinner, Moritz F., additional, Schlüter, Michael, additional, Nordbeck, Peter, additional, Eckardt, Lars, additional, Bogossian, Harilaos, additional, Sultan, Arian, additional, Wenzel, Beate, additional, Kuck, Karl-Heinz, additional, Piorkowski, C., additional, Lebedev, D., additional, Kautzner, J., additional, Sticherling, C., additional, Deneke, T., additional, Rostock, T., additional, Ukena, C., additional, Kuniss, M., additional, Makimoto, H., additional, Hindricks, G., additional, Bänsch, D., additional, Schreieck, J., additional, Kolb, C., additional, Geller, J., additional, Pokushalov, E., additional, Gutleben, K., additional, Sommer, P., additional, Boldt, L.H., additional, and Parwani, A., additional

Published
2020
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239. Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation

Author

Shoemaker, M. Benjamin, primary, Husser, Daniela, additional, Roselli, Carolina, additional, Al Jazairi, Meelad, additional, Chrispin, Jonathan, additional, Kühne, Michael, additional, Neumann, Benjamin, additional, Knight, Stacey, additional, Sun, Han, additional, Mohanty, Sanghamitra, additional, Shaffer, Christian, additional, Thériault, Sébastien, additional, Rinke, Lauren Lee, additional, Siland, Joylene E., additional, Crawford, Diane M., additional, Ueberham, Laura, additional, Zardkoohi, Omeed, additional, Büttner, Petra, additional, Geelhoed, Bastiaan, additional, Blum, Steffen, additional, Aeschbacher, Stefanie, additional, Smith, Jonathan D., additional, Van Wagoner, David R., additional, Freudling, Rebecca, additional, Müller-Nurasyid, Martina, additional, Montgomery, Jay, additional, Yoneda, Zachary, additional, Wells, Quinn, additional, Issa, Tariq, additional, Weeke, Peter, additional, Jacobs, Victoria, additional, Van Gelder, Isabelle C., additional, Hindricks, Gerhard, additional, Barnard, John, additional, Calkins, Hugh, additional, Darbar, Dawood, additional, Michaud, Greg, additional, Kääb, Stefan, additional, Ellinor, Patrick, additional, Natale, Andrea, additional, Chung, Mina, additional, Nazarian, Saman, additional, Cutler, Michael J., additional, Sinner, Moritz F., additional, Conen, David, additional, Rienstra, Michiel, additional, Bollmann, Andreas, additional, Roden, Dan M., additional, and Lubitz, Steven, additional

Published
2020
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241. Continued misuse of orphan drug legislation: a life-threatening risk for mexiletine

Author

Postema, Pieter G, primary, Schwartz, Peter J, additional, Arbelo, Elena, additional, Bannenberg, Wilbert J, additional, Behr, Elijah R, additional, Belhassen, Bernard, additional, Brugada, Josep, additional, Brugada, Pedro, additional, John Camm, A, additional, Casado-Arroyo, Ruben, additional, ‘t Hoen, Ellen, additional, Hollak, Carla E M, additional, Kääb, Stefan, additional, Lambiase, Pier D, additional, Leenhardt, Antoine, additional, Priori, Silvia G, additional, Probst, Vincent, additional, Stunnenberg, Bas C, additional, Tfelt-Hansen, Jacob, additional, Van Engelen, Baziel G M, additional, Veltmann, Christian, additional, Viskin, Sami, additional, and Wilde, Arthur A M, additional

Published
2020
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243. Quantitative assessment of cardiac 123iodo-metaiodobenzylguanidine SPECT/CT in patients with arrhythmogenic right ventricular cardiomyopathy: Novel insight in disease monitoring.

Author

Hagen, Johannes M., Zacherl, Mathias J., Brendel, Matthias, Clauß, Sebastian, Kääb, Stefan, Bartenstein, Peter, Todica, Andrei, Böning, Guido, and Fischer, Maximilian

Abstract

The heart-to-mediastinum ratio (H/M-Ratio) of 123iodo-metaiodobenzylguanidine (123I-MIBG) represents state-of-the-art assessment for sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to evaluate quantitative reconstruction of 123I-MIBG uptake and to demonstrate its correlation with echocardiographic parameters. Cardiac innervation was assessed in 23 patients diagnosed with definite ARVC or borderline ARVC and 12 patients with other cardiac disease presenting arrhythmia, using quantitative 123I-MIBG Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) imaging. Tracer uptake was evaluated in the left (LV) and right ventricle (RV) based on a CT scan after quantitative image reconstruction. The relationship between tracer uptake and echocardiographic parameter data was examined. Absolute quantification of 123I-MIBG uptake in the LV and RV is feasible and correlates accurately with the gold standard H/M Ratio. When comparing sensitivity and specificity, the area under the curve (AUC) favors standardized uptake value (SUV) of the RV over the right-ventricle-to-mediastinum-ratio (RV/M-Ratio) for diagnosing ARVC. A reduced RV-SUV in patients with definite ARVC is associated with reduced RV function. RV polar maps revealed globally reduced 123I-MIBG uptake without segment-specific reduction in the RV. Quantitative 123I-MIBG SPECT in ARCV patients offers robust potential for clinical reporting and demonstrates a significant correlation with RV function. Segmental RV analysis needs to be evaluated in larger samples. In summary, cardiac 123I-MIBG imaging using SUV could facilitate image-guided therapy in patients diagnosed with ARVC. [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2024
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244. Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

Author

Pulit, Sara L., Weng, Lu-Chen, McArdle, Patrick F, Trinquart, Ludovic, Choi, Seung Hoan, Mitchell, Braxton D., Rosand, Jonathan, de Bakker, Paul I W, Benjamin, Emelia J, Ellinor, Patrick T, Kittner, Steven J, Lubitz, Steven A, Anderson, Christopher D, Christophersen, Ingrid E., Rienstra, Michiel, Roselli, Carolina, Yin, Xiaoyan, Geelhoed, Bastiaan, Barnard, John, Lin, Honghuang, Arking, Dan E., Smith, Albert V., Albert, Christine M., Chaffin, Mark, Tucker, Nathan R., Li, Molong, Klarin, Derek, Bihlmeyer, Nathan A, Low, Siew-Kee, Weeke, Peter E., Müller-Nurasyid, Martina, Smith, J. Gustav, Brody, Jennifer A., Niemeijer, Maartje N., Dörr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E., Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Malik, Rainer, Horimoto, Andrea R. V. R., Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Thériault, Sébastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J., Shah, Svati, Siland, Joylene E., Kubo, Michiaki, Smith, Jonathan D., Van Wagoner, David R., Bis, Joshua C., Perz, Siegfried, Psaty, Bruce M., Ridker, Paul M., Magnani, Jared W., Harris, Tamara B., Launer, Lenore J., Shoemaker, M. Benjamin, Padmanabhan, Sandosh, Haessler, Jeffrey, Bartz, Traci M., Waldenberger, Melanie, Lichtner, Peter, Arendt, Marina, Krieger, Jose E., Kähönen, Mika, Risch, Lorenz, Mansur, Alfredo J., Peters, Annette, Smith, Blair H., Lind, Lars, Scott, Stuart A., Lu, Yingchang, Bottinger, Erwin B., Hernesniemi, Jussi, Lindgren, Cecilia M., Wong, Jorge A, Huang, Jie, Eskola, Markku, Morris, Andrew P., Ford, Ian, Reiner, Alex P., Delgado, Graciela, Chen, Lin Y., Chen, Yii-Der Ida, Sandhu, Roopinder K., Li, Man, Boerwinkle, Eric, Eisele, Lewin, Lannfelt, Lars, Rost, Natalia, Orho-Melander, arju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C., Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W., Heilmann, Stefanie, Almgren, Peter, Huang, Paul L., Sotoodehnia, Nona, Soliman, Elsayed Z., Uitterlinden, Andre G., Hofman, Albert, Franco, Oscar H., Völker, Uwe, Jöckel, Karl-Heinz, Sinner, Moritz F., Lin, Henry J., Guo, Xiuqing, Dichgans, Martin, Ingelsson, Erik, Kooperberg, Charles, Melander, Olle, Loos, Ruth J. F., Laurikka, Jari, Conen, David, Harst, Pim van der, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J. Wouter, Hayward, Caroline, Rotter, Jerome I., März, Winfried, Lehtimäki, Terho, Stricker, Bruno H., Chung, Mina K., Felix, Stephan B., Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M., Sun, Albert, Anderson, Christopher D., Kääb, Stefan, Hopewell, Jemma C., Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B., Paré, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P., Verweij, Niek, Taylor, Kent D., Campbell, Archie, Magnusson, Patrik K., Porteous, David, Hocking, Lynne J., Vlachopoulou, Efthymia, Pedersen, Nancy L., Nikus, Kjell, Chasman, Daniel I., Heckbert, Susan R., Benjamin, Emelia J., Tanaka, Toshihiro, Lunetta, Kathryn L., Lubitz, Steven A., Ellinor, Patrick T., Smoller, Sylvia, Sorkin, John, Wang, Xingwu, Selim, Magdy, Pikula, Aleksandra, Wolf, Philip, Seshadri, Sudha, Bakker, Paul de, Chasman, Daniel, Rexrode, Kathryn, Chen, Ida, Rotter, Jerome, Luke, May, Sale, Michelle, Lee, Tsong-Hai, Chang, Ku-Chou, Elkind, Mitchell, Goldstein, Larry, James, Michael Luke, Breteler, Monique, O’Donnell, Chris, Leys, Didier, Carty, Cara, Kidwell, Chelsea, Olesen, Jes, Sharma, Pankaj, Rich, Stephen, Tatlisumak, Turgot, Happola, Olli, Bijlenga, Philippe, Soriano, Carolina, Giralt, Eva, Roquer, Jaume, Jimenez-Conde, Jordi, Cotlarcius, Ioana, Hardy, John, Korostynski, Michal, Boncoraglio, Giorgio, Ballabio, Elena, Parati, Eugenio, Mateusz, Adamski, Urbanik, Andrzej, Dziedzic, Tomasz, Jagiella, Jeremiasz, Gasowski, Jerzy, Wnuk, Marcin, Olszanecki, Rafael, Pera, Joanna, Slowik, Agnieszka, Juchniewicz, Karol Jozef, Levi, Christopher, Nyquist, Paul, Cendes, Iscia, Cabral, Norberto, Franca, Paulo, Goncalves, Anderson, Keller, Lina, Crisby, Milita, Kostulas, Konstantinos, Lemmens, Robin, Ahmadi, Kourosh, Opherk, Christian, Duering, Marco, Gonik, Mariya, Staals, Julie, Burri, Philippe, Sadr-Nabavi, Ariane, Romero, Javier, Biffi, Alessandro, Anderson, Chris, Falcone, Guido, Brouwers, Bart, Du, Rose, Kourkoulis, Christina, Battey, Thomas, Lubitz, Steven, Mueller-Myhsok, Bertram, Meschia, James, Brott, Thomas, Pare, Guillaume, Pichler, Alexander, Enzinger, Christian, Schmidt, Helena, Schmidt, Reinhold, Seiler, Stephan, Blanton, Susan, Yamada, Yoshiji, Bersano, Anna, Rundek, Tatjana, Sacco, Ralph, Chan, Yu-Feng Yvonne, Gschwendtner, Andreas, Deng, Zhen, Barr, Taura, Gwinn, Katrina, Corriveau, Roderick, Singleton, Andrew, Waddy, Salina, Launer, Lenore, Chen, Christopher, Le, Kim En, Lee, Wei Ling, Tan, Eng King, Olugbodi, Akintomi, Rothwell, Peter, Schilling, Sabrina, Mok, Vincent, Lebedeva, Elena, Jern, Christina, Jood, Katarina, Olsson, Sandra, Kim, Helen, Lee, Chaeyoung, Kilarski, Laura, Markus, Hugh, Peycke, Jennifer, Bevan, Steve, Sheu, Wayne, Chiou, Hung Yi, Chern, Joseph, Giraldo, Elias, Taqi, Muhammad, Jain, Vivek, Lam, Olivia, Howard, George, Woo, Daniel, Kittner, Steven, Mitchell, Braxton, Cole, John, O’Connell, Jeff, Milewicz, Dianna, Illoh, Kachikwu, Worrall, Bradford, Stine, Colin, Karaszewski, Bartosz, Werring, David, Sofat, Reecha, Smalley, June, Lindgren, Arne, Hansen, Bjorn, Norrving, Bo, Smith, Gustav, Martin, Juan Jose, Thijs, Vincent, Klijn, Karin, van’t Hof, Femke, Algra, Ale, Macleod, Mary, Perry, Rodney, Arnett, Donna, Pezzini, Alessandro, Padovani, Alessandro, Cramer, Steve, Fisher, Mark, Saleheen, Danish, Broderick, Joseph, Kissela, Brett, Doney, Alex, Cathie, Sudlow, Rannikmae, Kristiina, Silliman, Scott, McDonough, Caitrin, Walters, Matthew, Pedersen, Annie, Nakagawa, Kazuma, Chang, Christy, Dobbins, Mark, McArdle, Patrick, Chang, Yu-Ching, Brown, Robert, Brown, Devin, Holliday, Elizabeth, Kalaria, Raj, Maguire, Jane, John, Attia, Farrall, Martin, Giese, Anne-Katrin, Fornage, Myriam, Majersik, Jennifer, Cushman, Mary, Keene, Keith, Bennett, Siiri, Tirschwell, David, Psaty, Bruce, Reiner, Alex, Longstreth, Will, Spence, David, Montaner, Joan, Fernandez-Cadenas, Israel, Langefeld, Carl, Bushnell, Cheryl, Heitsch, Laura, Lee, Jin-Moo, Sheth, Kevin, Cardiovascular Centre (CVC), Department of Medicine, Clinicum, Transplantation Laboratory, Medicum, Neurologian yksikkö, Department of Neurosciences, University of Helsinki, Doctoral Programme in Clinical Research, HUS Neurocenter, Epidemiology, Internal Medicine, Klinische Neurowetenschappen, RS: CARIM - R3.03 - Cerebral small vessel disease, and MUMC+: MA Med Staf Spec Neurologie (9)

Subjects
Medizin, 030204 cardiovascular system & hematology, VARIANTS, 3124 Neurology and psychiatry, 0302 clinical medicine, Epidemiology, Genotype, EPIDEMIOLOGY, Stroke, Genetics (clinical), 0303 health sciences, Aspirin, Atrial fibrillation, ASSOCIATION, 3. Good health, LIFETIME RISK, ISCHEMIC-STROKE, Cardiology, Biomarker (medicine), Medical genetics, BURDEN, Medical Genetics, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Clinical Neurology, Single-nucleotide polymorphism, Article, 03 medical and health sciences, Internal medicine, Genetic predisposition, medicine, SNP, cardiovascular diseases, Genotyping, 030304 developmental biology, Genetic association, Medicinsk genetik, Science & Technology, business.industry, 3112 Neurosciences, Heritability, medicine.disease, PREVENTION, ASPIRIN, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery, CAUSATIVE CLASSIFICATION
Abstract

ObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 × 10−4 in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 × 10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07, p = 0.004), but no other primary stroke subtypes (all p > 0.1).ConclusionsGenetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

Published
2018

245. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author

Prins, Bram P, Mead, Timothy J, Brody, Jennifer A, Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A, van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T, Gabriel, George C, Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M, Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching-Ti, Lyytikäinen, Leo-Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V, Verweij, Niek, Warren, Helen R, Weiss, Stefan, Alonso, Alvaro, Arnar, David O, Bots, Michiel L, de Boer, Rudolf A, Dominiczak, Anna F, Eijgelsheim, Mark, Ellinor, Patrick T, Guo, Xiuqing, Felix, Stephan B, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Huang, Paul L, Jukema, JW, Kähönen, Mika, Kors, Jan A, Lambiase, Pier D, Launer, Lenore J, Li, Man, Linneberg, Allan, Nelson, Christopher P, Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M, Raitakari, Olli T, Rice, Kenneth M, Rotter, Jerome I, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Tim D, Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G, Xie, Zhijun, Asselbergs, Folkert W, Dörr, Marcus, van Duijn, Cornelia M, Gasparini, Paolo, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J, Lubitz, Steven A, Mook-Kanamori, Dennis O, Conti, Francesco J, Newton-Cheh, Christopher H, Rosand, Jonathan, Rudan, Igor, and Samani, Nilesh J

Subjects
Male, Bioinformatics, Gene Expression, Black People, Conduction, Cardiovascular, White People, Mice, Electrocardiography, Open Reading Frames, ADAMTS Proteins, Heart Conduction System, Information and Computing Sciences, Exome Sequencing, Genetics, Animals, Humans, 2.1 Biological and endogenous factors, Exome, Polymorphism, Aetiology, Myocardium, Gene Expression Profiling, Human Genome, Single Nucleotide, Middle Aged, Biological Sciences, Exome chip, Meta-analysis, Heart Disease, Genetic Loci, Connexin 43, ADAMTS6, Female, Environmental Sciences, Genome-Wide Association Study
Abstract

BackgroundGenome-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.ResultsHere, 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 111,874individuals 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.ConclusionsOur approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.

Published
2018

247. Single chamber implantable cardioverter defibrillator compared to dual chamber implantable cardioverter defibrillator: less is more! Data from the German Device Registry

Author

Bogossian, Harilaos, primary, Frommeyer, Gerrit, additional, Hochadel, Matthias, additional, Ince, Hüseyin, additional, Spitzer, Stefan G., additional, Eckardt, Lars, additional, Maier, Sebastian K. G., additional, Kleemann, Thomas, additional, Brachmann, Johannes, additional, Stellbrink, Christoph, additional, Gonska, Bernd-Dieter, additional, Kääb, Stefan, additional, Senges, Jochen, additional, and Lemke, Bernd, additional

Published
2019
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248. Catch-up-ESUS - follow-up in embolic stroke of undetermined source (ESUS) in a prospective, open-label, observational study: study protocol and initial baseline data

Author

Feil, Katharina, primary, Heinrich, Johanna, additional, Küpper, Clemens, additional, Müller, Katharina, additional, Laub, Christoph, additional, von Falkenhausen, Aenne S, additional, Becker, Regina, additional, Wollenweber, Frank A, additional, Kääb, Stefan, additional, Sinner, Moritz F, additional, and Kellert, Lars, additional

Published
2019
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249. 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, Markus, primary, Schlögl, Simon, additional, Lubinski, Andrzej, additional, Svendsen, Jesper Hastrup, additional, Bauer, Axel, additional, Arbelo, Elena, additional, Brusich, Sandro, additional, Conen, David, additional, Cygankiewicz, Iwona, additional, Dommasch, Michael, additional, Flevari, Panagiota, additional, Galuszka, Jan, additional, Hansen, Jim, additional, Hasenfuß, Gerd, additional, Hatala, Robert, additional, Huikuri, Heikki V., additional, Kenttä, Tuomas, additional, Kucejko, Tomasz, additional, Haarmann, Helge, additional, Harden, Markus, additional, Iovev, Svetoslav, additional, Kääb, Stefan, additional, Kaliska, Gabriela, additional, Katsimardos, Andreas, additional, Kasprzak, Jaroslaw D., additional, Qavoq, Dariusz, additional, Lüthje, Lars, additional, Malik, Marek, additional, Novotný, Tomáš, additional, Pavlović, Nikola, additional, Perge, Peter, additional, Röver, Christian, additional, Schmidt, Georg, additional, Shalganov, Tchavdar, additional, Sritharan, Rajeeva, additional, Svetlosak, Martin, additional, Sallo, Zoltan, additional, Szavits-Nossan, Janko, additional, Traykov, Vassil, additional, Vandenberk, Bert, additional, Velchev, Vasil, additional, Vos, Marc A., additional, Willich, Stefan N., additional, Friede, Tim, additional, Willems, Rik, additional, Merkely, Béla, additional, and Sticherling, Christian, additional

Published
2019
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250. Prediction of mortality benefit based on periodic repolarisation dynamics in patients undergoing prophylactic implantation of a defibrillator: a prospective, controlled, multicentre cohort study

Author

Bauer, Axel, primary, Klemm, Mathias, additional, Rizas, Konstantinos D, additional, Hamm, Wolfgang, additional, von Stülpnagel, Lukas, additional, Dommasch, Michael, additional, Steger, Alexander, additional, Lubinski, Andrezej, additional, Flevari, Panagiota, additional, Harden, Markus, additional, Friede, Tim, additional, Kääb, Stefan, additional, Merkely, Bela, additional, Sticherling, Christian, additional, Willems, Rik, additional, Huikuri, Heikki, additional, Malik, Marek, additional, Schmidt, Georg, additional, Zabel, Markus, additional, Merkely, Béla, additional, Perge, Peter, additional, Sallo, Zoltan, additional, Szeplaki, Gabor, additional, Lüthje, Lars, additional, Schlögl, Simon, additional, Haarmann, Helge, additional, Bergau, Leonard, additional, Seegers, Joachim, additional, Hasenfuß, Gerd, additional, Munoz-Exposito, Pascal, additional, Tichelbäcker, Tobias, additional, Kirova, Aleksandra, additional, Hnatkova, Katerina, additional, Vos, Marc, additional, Willich, Stefan N., additional, Reinhold, Thomas, additional, Vandenberk, Bert, additional, Klinika, Magdalena, additional, Toplice, Krapinske, additional, Flevari, Panayota, additional, Katsimardos, Andreas, additional, Katsaras, Dimitrios, additional, Hatala, Robert, additional, Svetlosak, Martin, additional, Lubinski, Andrzej, additional, Kuczejko, Tomasz, additional, Hansen, Jim, additional, Conen, David, additional, Milosrdnice, Sestre, additional, Pavlović, Nikola, additional, Manola, Šime, additional, Vinter, Ozren, additional, Benko, Ivica, additional, Tuinenburg, Anton, additional, Bauer, Axel, additional, Meyer-Zürn, Christine, additional, Eick, Christian, additional, Hastrup, Jesper, additional, Brugada, Josep, additional, Arbelo, Elena, additional, Kaliska, Gabriela, additional, Martinek, Jozef, additional, Sinner, Moritz F., additional, Rizas, Konstantinos D., additional, Vdovin, Nikolay, additional, Cygankiewicz, Iwona, additional, Ptaszynski, Pawel, additional, Kaczmarek, Krzysztof, additional, Poddebska, Izabela, additional, Iovev, Svetoslav, additional, Novotný, Tomáš, additional, Kozak, Milan, additional, Kenttä, Tuomas, additional, Pelli, Ari, additional, Kasprzak, Jaroslaw D., additional, Qavoq, Dariusz, additional, Brusich, Sandro, additional, Avdovic, Ervin, additional, Klasan, Marina, additional, Galuszka, Jan, additional, Taborsky, Milos, additional, Velchev, Vasil, additional, Dissmann, Rüdiger, additional, Guzik, Przemysław, additional, Bimmel, Dieter, additional, Lieberz, Christiane, additional, Stefanow, Stefan, additional, Rüb, Norman, additional, Wolpert, Christian, additional, Maier, Lars S., additional, Behrens, Steffen, additional, Jurisic, Zrinka, additional, Braunschweig, Frieder, additional, Blaschke, Florian, additional, Pieske, Burkert, additional, Bakotic, Zoran, additional, Anic, Ante, additional, Schwinger, Robert H.G., additional, and Platonov, Pyotr, additional

Published
2019
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