29 results on '"Kanters, Jorgen"'
Search Results
2. Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals
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Noordam, Raymond, Young, William J., Salman, Reem, Kanters, Jørgen K., van den Berg, Marten E., van Heemst, Diana, Lin, Henry J., Barreto, Sandhi Maria, Biggs, Mary L., Biino, Ginevra, Catamo, Eulalia, Concas, Maria Pina, Ding, Jun, Evans, Daniel S., Foco, Luisa, Grarup, Niels, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Mei, Hao, van der Most, Peter J., Müller-Nurasyid, Martina, Nelson, Christopher P., Qian, Yong, Repetto, Linda, Said, M. Abdullah, Shah, Nabi, Schramm, Katharina, Vidigal, Pedro G., Weiss, Stefan, Yao, Jie, Zilhao, Nuno R., Brody, Jennifer A., Braund, Peter S., Brumat, Marco, Campana, Eric, Christofidou, Paraskevi, Caulfield, Mark J., De Grandi, Alessandro, Dominiczak, Anna F., Doney, Alex S.F., Eiriksdottir, Gudny, Ellervik, Christina, Giatti, Luana, Gögele, Martin, Graff, Claus, Guo, Xiuqing, van der Harst, Pim, Joshi, Peter K., Kähönen, Mika, Kestenbaum, Bryan, Lima-Costa, Maria F., Linneberg, Allan, Maan, Arie C., Meitinger, Thomas, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Petersmann, Astrid, Sever, Peter, Sinner, Mortiz F., Shen, Xia, Stanton, Alice, Strauch, Konstantin, Soliman, Elsayed Z., Tarasov, Kirill V., Taylor, Kent D., Thio, Chris H.L., Uitterlinden, André G., Vaccargiu, Simona, Waldenberger, Melanie, Robino, Antonietta, Correa, Adolfo, Cucca, Francesco, Cummings, Steven R., Dörr, Marcus, Girotto, Giorgia, Gudnason, Vilmundur, Hansen, Torben, Heckbert, Susan R., Juhl, Christian R., Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Lotufo, Paulo A., Palmer, Colin N.A., Pirastu, Mario, Pramstaller, Peter P., Ribeiro, Antonio Luiz P., Rotter, Jerome I., Samani, Nilesh J., Snieder, Harold, Spector, Tim D., Stricker, Bruno H., Verweij, Niek, Wilson, James F., Wilson, James G., Jukema, J. Wouter, Tinker, Andrew, Newton-Cheh, Christopher H., Sotoodehnia, Nona, Mook-Kanamori, Dennis O., Munroe, Patricia B., and Warren, Helen R.
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- 2019
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3. Tilt-table testing of patients with pacemaker and recurrent syncope
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Haarmark, Christian, Kanters, Jørgen K., and Mehlsen, Jesper
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- 2015
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4. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
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Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
- Abstract
The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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- 2022
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5. Association of Levothyroxine Treatment and Thyroid Peroxidase Antibodies with Antidepressant Use:A Danish Population-Based Longitudinal Study
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Jensen, Christian Zinck, la Cour, Jeppe Lerche, Watt, Torquil, Kanters, Jorgen Kim, Poulsen, Henrik Enghusen, Faber, Jens, Ellervik, Christina, Nygaard, Birte, Jensen, Christian Zinck, la Cour, Jeppe Lerche, Watt, Torquil, Kanters, Jorgen Kim, Poulsen, Henrik Enghusen, Faber, Jens, Ellervik, Christina, and Nygaard, Birte
- Abstract
Background: Subjects receiving levothyroxine (LT4) treatment have increased prevalence of depression, anxiety, and antidepressant use, but whether the underlying mechanism relates to thyroid autoimmunity is still unclarified.Methods: This is a population-based longitudinal study. Baseline biochemical and questionnaire data from the Danish General Suburban Population Study (GESUS) in 2010-2013 were linked with individual-level longitudinal data in national health registries. The aim was to investigate the associations between thyroid peroxidase antibodies (TPOAbs) and LT4 treatment, separately and through interaction, and at least one redeemed prescription for antidepressants. Logistic and Cox regression were used to evaluate initiation of antidepressant use before and after the baseline examination in GESUS, respectively. All exposures and covariates were fixed at the date of baseline examination. Thyroid autoimmunity was defined as serum TPOAbs >60 U/mL. Adjustments included sex, age, education, income, Charlson comorbidity index, smoking, and alcohol. Sensitivity analyses were performed for missing variables, exclusion of lithium use, exclusion of thyroid surgery, and conservative definitions for LT4 treatment and antidepressant use requiring at least two prescriptions.Results: We included 12,894 individuals, of whom 2353 (18%) had "past or current" antidepressant use at baseline, leaving 10,541 individuals at risk for incident antidepressant use after baseline. The median follow-up was 7.8 years during which 783 individuals (7.4% of 10,541 individuals) had incident antidepressant use. TPOAb positivity was not associated with "past or current" (odds ratio [OR] 0.90 [confidence interval, CI 0.78-1.03], p = 0.13) nor incident antidepressant use (hazard ratio [HR] 1.02 [CI 0.83-1.25], p = 0.88). LT4 treatment was associated with increased "past or current" antidepressant use (OR 1.33 [CI 1.10-1.62], p = 0.004) and increased incident antidepressant use (HR 1.38
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- 2022
6. Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes
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Taubel, Jorg, Pimenta, Dominic, Cole, Samuel Thomas, Graff, Claus, Kanters, Jorgen K., Camm, A. John, Taubel, Jorg, Pimenta, Dominic, Cole, Samuel Thomas, Graff, Claus, Kanters, Jorgen K., and Camm, A. John
- Abstract
Background Patients with Type 1 diabetes mellitus have been shown to be at a two to ten-fold higher risk of sudden cardiac death (SCD) (Svane et al., Curr Cardiol 2020; 22:112) than the general population, but the underlying mechanism is unclear. Hyperglycaemia is a recognised cause of QTc prolongation; a state patients with type 1 diabetes are more prone to, potentially increasing their risk of ventricular arrhythmia. Understanding the QTc prolongation effect of both hyperglycaemia and the concomitant additive risk of commonly prescribed QTc-prolonging drugs such as Moxifloxacin may help to elucidate the mechanism of sudden cardiac death in this cohort. This single-blinded, placebo-controlled study investigated the extent to which hyperglycaemia prolongs the QTc in controlled conditions, and the potential additive risk of QTc-prolonging medications.Methods 21 patients with type 1 diabetes mellitus were enrolled to a placebo-controlled crossover study at a single clinical trials unit. Patients underwent thorough QTc assessment throughout the study. A 'hyperglycaemic clamp' of oral and intravenous glucose was administered with a target blood glucose of > 25 mM and maintained for 2 h on day 1 and day 3, alongside placebo on day 1 and moxifloxacin on day 3. Day 2 served as a control day between the two active treatment days. Thorough QTc assessment was conducted at matched time points over 3 days, and regular blood sampling was undertaken at matched time intervals for glucose levels and moxifloxacin exposure.Results Concentration-effect modelling showed that acute hyperglycaemia prolonged the QTc interval in female and male volunteers with type 1 diabetes by a peak mean increase of 13 ms at 2 h. Peak mean QTc intervals after the administration of intravenous Moxifloxacin during the hyperglycaemic state were increased by a further 9 ms at 2 h, to 22 ms across the entire study population. Regression analysis suggested this additional increase was addi
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- 2022
7. Celebrities in the heart, strangers in the pancreatic beta cell:Voltage-gated potassium channels Kv7.1 and Kv11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes
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Lubberding, Anniek F., Juhl, Christian R., Skovhoj, Emil Z., Kanters, Jorgen K., Mandrup-Poulsen, Thomas, Torekov, Signe S., Lubberding, Anniek F., Juhl, Christian R., Skovhoj, Emil Z., Kanters, Jorgen K., Mandrup-Poulsen, Thomas, and Torekov, Signe S.
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Voltage-gated potassium (K-v) channels play an important role in the repolarization of a variety of excitable tissues, including in the cardiomyocyte and the pancreatic beta cell. Recently, individuals carrying loss-of-function (LoF) mutations in KCNQ1, encoding K(v)7.1, and KCNH2 (hERG), encoding K(v)11.1, were found to exhibit post-prandial hyperinsulinaemia and episodes of hypoglycaemia. These LoF mutations also cause the cardiac disorder long QT syndrome (LQTS), which can be aggravated by hypoglycaemia. Interestingly, patients with LQTS also have a higher burden of diabetes compared to the background population, an apparent paradox in relation to the hyperinsulinaemic phenotype, and KCNQ1 has been identified as a type 2 diabetes risk gene. This review article summarizes the involvement of delayed rectifier K+ channels in pancreatic beta cell function, with emphasis on K(v)7.1 and K(v)11.1, using the cardiomyocyte for context. The functional and clinical consequences of LoF mutations and polymorphisms in these channels on blood glucose homeostasis are explored using evidence from pre-clinical, clinical and genome-wide association studies, thereby evaluating the link between LQTS, hyperinsulinaemia and type 2 diabetes.
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- 2022
8. Abstract 13222: Genetic Variants Close to NKX2-5 and MYH6 Are Associated With AV Nodal Reentry Tachycardia in First Genome-Wide Association Study
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Andreasen, Laura, primary, Ahlberg, Gustav, additional, Lundegaard, Pia Rengtved, additional, Ægisdottir, Hildur, additional, Hartmann, Jacob Peter, additional, Paludan-Mueller, Christian, additional, Hadji-Turdeghal, Katra, additional, Ghouse, Jonas, additional, Pehrson, Steen, additional, Jensen, Henrik, additional, Riahi, Sam, additional, Hansen, Jim, additional, Sandgaard, Niels, additional, Haunso, stig, additional, Kanters, Jorgen, additional, Ellervik, Christina, additional, Bundgaard, Henning, additional, Ullum, Henrik, additional, Holm, Hilma, additional, Arnar, David, additional, Svendsen, Jesper Hastrup, additional, and Olesen, Morten, additional
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- 2021
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9. Abstract 13983: Beta-Blocker Adherence Among Patients With Congenital Long QT Syndrome: A Nationwide Study
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Kroell, Johanna, primary, Jensen, Henrik, additional, Tfelt-hansen, Jacob, additional, Torp-Pedersen, Christian, additional, Fosbøl, Emil, additional, Koeber, lars, additional, Kanters, Jorgen, additional, Jespersen, Camilla, additional, Gislason, Gunnar, additional, Butt, Jawad, additional, Bundgaard, Henning, additional, and Weeke, Peter E, additional
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- 2021
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10. Abstract 12381: Clinical Implications of SCN5A and SCN10A Loss of Function Variants in 169,610 Exomes Representing the General Population
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Paludan-Mueller, Christian, primary, Larsen, Simon, additional, Ahlberg, Gustav, additional, Andreasen, Laura, additional, Svendsen, Jesper Hastrup H, additional, Kanters, Jorgen K, additional, and Olesen, Morten S, additional
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- 2021
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11. Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
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Walsh, Roddy, Lahrouchi, Najim, Tadros, Rafik, Kyndt, Florence, Glinge, Charlotte, Postema, Pieter G., Amin, Ahmad S., Nannenberg, Eline A., Ware, James S., Whiffin, Nicola, Mazzarotto, Francesco, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, Bos, J. Martijn, Breckpot, Jeroen, Campuzano, Oscar, Castelletti, Silvia, Celen, Candan, Clauss, Sebastian, Corveleyn, Anniek, Crotti, Lia, Dagradi, Federica, de Asmundis, Carlo, Denjoy, Isabelle, Dittmann, Sven, Ellinor, Patrick T., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen K., Kimoto, Hiroki, Kotta, Maria-Christina, Krapels, Ingrid P. C., Kurabayashi, Masahiko, Lazarte, Julieta, Leenhardt, Antoine, Loeys, Bart L., Lundin, Catarina, Makiyama, Takeru, Mansourati, Jacques, Martins, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, Sahin, Hatice, Sarquella-Brugada, Georgia, Sebastiano, Regina, Sharma, Sanjay, Sheppard, Mary N., Shimamoto, Keiko, Shoemaker, M. Benjamin, Stallmeyer, Birgit, Steinfurt, Johannes, Tanaka, Yuji, Tester, David J., Usuda, Keisuke, van der Zwaag, Paul A., Van Dooren, Sonia, Van Laer, Lut, Winbo, Annika, Winkel, Bo G., Yamagata, Kenichiro, Zumhagen, Sven, Volders, Paul G. A., Lubitz, Steven A., Antzelevitch, Charles, Platonov, Pyotr G., Odening, Katja E., Roden, Dan M., Roberts, Jason D., Skinner, Jonathan R., Tfelt-Hansen, Jacob, van den Berg, Maarten P., Olesen, Morten S., Lambiase, Pier D., Borggrefe, Martin, Hayashi, Kenshi, Rydberg, Annika, Nakajima, Tadashi, Yoshinaga, Masao, Saenen, Johan B., Kaeaeb, Stefan, Brugada, Pedro, Robyns, Tomas, Giachino, Daniela F., Ackerman, Michael J., Brugada, Ramon, Brugada, Josep, Gimeno, Juan R., Hasdemir, Can, Guicheney, Pascale, Priori, Silvia G., Schulze-Bahr, Eric, Makita, Naomasa, Schwartz, Peter J., Shimizu, Wataru, Aiba, Takeshi, Schott, Jean-Jacques, Redon, Richard, Ohno, Seiko, Probst, Vincent, Behr, Elijah R., Barc, Julien, Bezzina, Connie R., Walsh, Roddy, Lahrouchi, Najim, Tadros, Rafik, Kyndt, Florence, Glinge, Charlotte, Postema, Pieter G., Amin, Ahmad S., Nannenberg, Eline A., Ware, James S., Whiffin, Nicola, Mazzarotto, Francesco, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, Bos, J. Martijn, Breckpot, Jeroen, Campuzano, Oscar, Castelletti, Silvia, Celen, Candan, Clauss, Sebastian, Corveleyn, Anniek, Crotti, Lia, Dagradi, Federica, de Asmundis, Carlo, Denjoy, Isabelle, Dittmann, Sven, Ellinor, Patrick T., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen K., Kimoto, Hiroki, Kotta, Maria-Christina, Krapels, Ingrid P. C., Kurabayashi, Masahiko, Lazarte, Julieta, Leenhardt, Antoine, Loeys, Bart L., Lundin, Catarina, Makiyama, Takeru, Mansourati, Jacques, Martins, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, Sahin, Hatice, Sarquella-Brugada, Georgia, Sebastiano, Regina, Sharma, Sanjay, Sheppard, Mary N., Shimamoto, Keiko, Shoemaker, M. Benjamin, Stallmeyer, Birgit, Steinfurt, Johannes, Tanaka, Yuji, Tester, David J., Usuda, Keisuke, van der Zwaag, Paul A., Van Dooren, Sonia, Van Laer, Lut, Winbo, Annika, Winkel, Bo G., Yamagata, Kenichiro, Zumhagen, Sven, Volders, Paul G. A., Lubitz, Steven A., Antzelevitch, Charles, Platonov, Pyotr G., Odening, Katja E., Roden, Dan M., Roberts, Jason D., Skinner, Jonathan R., Tfelt-Hansen, Jacob, van den Berg, Maarten P., Olesen, Morten S., Lambiase, Pier D., Borggrefe, Martin, Hayashi, Kenshi, Rydberg, Annika, Nakajima, Tadashi, Yoshinaga, Masao, Saenen, Johan B., Kaeaeb, Stefan, Brugada, Pedro, Robyns, Tomas, Giachino, Daniela F., Ackerman, Michael J., Brugada, Ramon, Brugada, Josep, Gimeno, Juan R., Hasdemir, Can, Guicheney, Pascale, Priori, Silvia G., Schulze-Bahr, Eric, Makita, Naomasa, Schwartz, Peter J., Shimizu, Wataru, Aiba, Takeshi, Schott, Jean-Jacques, Redon, Richard, Ohno, Seiko, Probst, Vincent, Behr, Elijah R., Barc, Julien, and Bezzina, Connie R.
- Abstract
Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 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.
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- 2021
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12. DeepSynthBody:The beginning of the end for data deficiency in medicine
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Thambawita, Vajira, Hicks, Steven A., Isaksen, Jonas, Stensen, Mette Haug, Haugen, Trine B., Kanters, Jorgen, Parasa, Sravanthi, De Lange, Thomas, Johansen, Havard D., Johansen, Dag, Hammer, Hugo L., Halvorsen, Pal, Riegler, Michael A., Thambawita, Vajira, Hicks, Steven A., Isaksen, Jonas, Stensen, Mette Haug, Haugen, Trine B., Kanters, Jorgen, Parasa, Sravanthi, De Lange, Thomas, Johansen, Havard D., Johansen, Dag, Hammer, Hugo L., Halvorsen, Pal, and Riegler, Michael A.
- Abstract
Limited access to medical data is a barrier on developing new and efficient machine learning solutions in medicine such as computer-aided diagnosis, risk assessments, predicting optimal treatments and home-based personal healthcare systems. This paper presents DeepSynthBody: a novel framework that overcomes some of the inherent restrictions and limitations of medical data by using deep generative adversarial networks to produce synthetic data with characteristics similar to the real data, so-called DeepSynth (deep synthetic) data. We show that DeepSynthBody can address two key issues commonly associated with medical data, namely privacy concerns (as a result of data protection rules and regulations) and the high costs of annotations. To demonstrate the full pipeline of applying DeepSynthBody concepts and user-friendly functionalities, we also describe a synthetic medical dataset generated and published using our framework. DeepSynthBody opens a new era of machine learning applications in medicine with a synthetic model of the human body.
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- 2021
13. A Phase 1 Study to Investigate the Effects of Cortexolone 17 alpha-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity
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Taubel, Jorg, Mazzetti, Alessandro, Ferber, Georg, Burch, William, Fernandes, Sara, Patel, Avani, Spencer, Christopher S., Freier, Anne, Graff, Claus, Kanters, Jorgen K., Camm, John, Taubel, Jorg, Mazzetti, Alessandro, Ferber, Georg, Burch, William, Fernandes, Sara, Patel, Avani, Spencer, Christopher S., Freier, Anne, Graff, Claus, Kanters, Jorgen K., and Camm, John
- Abstract
Cortexolone 17 alpha-propionate, also known as clascoterone, is a potent androgen receptor inhibitor intended for the topical treatment of skin diseases associated with androgenic pathway alterations. In nonclinical studies, cortexolone 17 alpha-propionate was found to have a weak inhibitory effect on human Ether-a-go-go-Related Gene (hERG) potassium channels, which are vital for normal electrical activity in the heart. When used in a cream formulation, little cortexolone 17 alpha-propionate is absorbed. However, the solution formulation developed for the treatment of androgenetic alopecia leads to a measurable systemic concentration and accumulation of the antiandrogen. This phase 1 study assessed the effect of cortexolone 17 alpha-propionate on the QTc interval using concentration-effect analysis and the effect of a meal on QTc to confirm assay sensitivity. Thirty-two volunteers were randomly assigned to receive the active drug or a matching vehicle as placebo. Participants were dosed twice daily on days 1 to 3 (225 mg applied topically as a 7.5% solution 12 hours apart) and once on day 4. Pharmacokinetic and electrocardiogram assessments were performed after supratherapeutic doses. Assay sensitivity was successfully confirmed by using the food effect on the QTc interval. The results of this concentration-QTc analysis demonstrate that cortexolone 17 alpha-propionate and its metabolite/degradation product had no effect on the QTc interval in the concentration range tested.
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- 2021
14. Automatic selection of the threshold value r for approximate entropy
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Lu, Sheng, Chen, Xinnian, Kanters, Jorgen K., Solomon, Irene C., and Chon, Ki H.
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Heart beat -- Measurement ,Brownian motion -- Evaluation ,Entropy (Information theory) -- Measurement ,Approximation theory -- Methods ,Learning models (Stochastic processes) -- Usage ,Monte Carlo method -- Usage ,Biological sciences ,Business ,Computers ,Health care industry - Abstract
Calculation of approximate entropy (ApEn) requires a priori determination of two unknown parameters, m and r. While the recommended values of r, in the range of 0.1-0.2 times the standard deviation of the signal, have been shown to be applicable for a wide variety of signals, in certain cases, r values within this prescribed range can lead to an incorrect assessment of the complexity of a given signal. To circumvent this limitation, we recently advocated finding the maximum ApEn value by assessing all values of r from 0 to 1, and found that maximum ApEn does not always occur within the prescribed range of r values. Our results indicate that finding the maximum ApEn leads to the correct interpretation of a signal's complexity. One major limitation, however, is that the calculation of all choices of r values is often impractical due to the computational burden. Our new method, based on a heuristic stochastic model, overcomes this computational burden, and leads to the automatic selection of the maximum ApEn value for any given signal. Based on Monte Carlo simulations, we derive general equations that can be used to estimate the maximum ApEn with high accuracy for a given value of m. Application to both synthetic and experimental data confirmed the advantages claimed with the proposed approach. Index Terms--Approximate entropy, bounded random process, Brownian motion, heart rate variability, nonlinear determinism.
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- 2008
15. Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine:A Meta-analysis
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Oscanoa, Teodoro J., Vidal, Xavier, Kanters, Jorgen K., Romero-Ortuno, Roman, Oscanoa, Teodoro J., Vidal, Xavier, Kanters, Jorgen K., and Romero-Ortuno, Roman
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Introduction Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown.Objective To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with HCQ.Data Sources PubMed, EMBASE, Google Scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv, Research Square) were searched for studies published between December 2019 and June 30, 2020.Methods Effect statistics were pooled using random effects. The quality of observational studies and randomized controlled trials was appraised with STROBE and the Cochrane Risk of Bias Assessment tools, respectively.Outcomes Critical LQT was defined as: (1) maximum QT corrected (QTc) >= 500 ms (if QRS = 550 ms (if QRS >= 120 ms), and (2) QTc increase >= 60 ms.Results In the 28 studies included (n = 9124), the frequency of LQT during HCQ treatment was 6.7% (95% confidence interval [CI]: 3.7-10.2). In 20 studies (n = 7825), patients were also taking other QT-prolonging drugs. The frequency of LQT in the other 8 studies (n = 1299) was 1.7% (95% CI: 0.3-3.9). Twenty studies (n = 6869) reported HCQ discontinuation due to LQT, with a frequency of 3.7% (95% CI: 1.5-6.6). The frequency of ventricular arrhythmias during HCQ treatment was 1.68% (127/7539) and that of arrhythmogenic death was 0.69% (39/5648). Torsades de Pointes occurred in 0.06% (3/5066). Patients aged 60 years were at highest risk of HCQ-associated LQT (P <0.001).Conclusions HCQ-associated cardiotoxicity in SARS-CoV-2 patients is uncommon but requires ECG monitoring, particularly in those aged > 60 years and/or taking other QT-prolonging drugs. (C) 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.
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- 2020
16. The relationship between serum potassium concentrations and electrocardiographic characteristics in 163,547 individuals from primary care
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Krogager, Maria Lukacs, Kragholm, Kristian, Skals, Regitze Kuhr, Mortensen, Rikke Normark, Polcwiartek, Christoffer, Graff, Claus, Nielsen, Jonas Bille, Kanters, Jorgen K., Holst, Anders Gaarsdal, Sogaard, Peter, Pietersen, Adrian, Torp-Pedersen, Christian, Hansen, Steen Moller, Krogager, Maria Lukacs, Kragholm, Kristian, Skals, Regitze Kuhr, Mortensen, Rikke Normark, Polcwiartek, Christoffer, Graff, Claus, Nielsen, Jonas Bille, Kanters, Jorgen K., Holst, Anders Gaarsdal, Sogaard, Peter, Pietersen, Adrian, Torp-Pedersen, Christian, and Hansen, Steen Moller
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Aims: Potassium disturbances are common and associated with increased morbidity and mortality, even in patients without prior cardiovascular disease. We examined six electrocardiographic (ECG) measures and their association to serum potassium levels. Methods and results: From the Copenhagen General Practitioners' Laboratory, we identified 163,547 individuals aged >= 16 years with a first available ECG and a concomitant serum potassium measurement during 2001-2011. Restricted cubic splines curves showed a non-linear relationship between potassium and the Fridericia corrected QT (QTcF) interval, T-wave amplitude, morphology combination score (MCS), PR interval, P-wave amplitude and duration. Therefore, potassium was stratified in two intervals K: 2.0-4.1 mmol/L and 4.2-6.0 mmol/L for further analyses. Within the low potassium range, we observed: QTcF was 12.8 ms longer for each mmol/L decrease in potassium (p < 0.0001); T-wave amplitude was 43.1 mu V lower for each mmol/L decrease in potassium (p < 0.0001); and MCS was 0.13 higher per mmol/L decrease in potassium (p < 0.001). Moreover, P-wave duration and PR interval were prolonged by 2.7 and 4.6 ms for each mmol/L decrease in potassium (p < 0.0001), respectively. Within the lowest potassium range (2.0-4.1 mmol/L) P-wave amplitude was 3.5 mu V higher for each mmol/L decrease in potassium (p < 0.0001). Within the high potassium range associations with the above-mentioned ECG parameters were much weaker. (C) 2018 Elsevier Inc. All rights reserved.
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- 2019
17. Stop-codon and C-terminal nonsense mutations are associated with a lower risk of cardiac events in patients with long QT syndrome type 1
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Ruwald, Martin H, Xu Parks, Xiaorong, Moss, Arthur J, Zareba, Wojciech, Baman, Jayson, McNitt, Scott, Kanters, Jorgen K, Shimizu, Wataru, Wilde, Arthur A, Jons, Christian, Lopes, Coeli M, Ruwald, Martin H, Xu Parks, Xiaorong, Moss, Arthur J, Zareba, Wojciech, Baman, Jayson, McNitt, Scott, Kanters, Jorgen K, Shimizu, Wataru, Wilde, Arthur A, Jons, Christian, and Lopes, Coeli M
- Abstract
BACKGROUND: In long QT syndrome type 1 (LQT1), the location and type of mutations have been shown to affect the clinical outcome. Although haploinsufficiency, including stop-codon and frameshift mutations, has been associated with a lower risk of cardiac events in patients with LQT1, nonsense mutations have been presumed functionally equivalent.OBJECTIVE: The purpose of this study was to evaluate clinical differences between patients with nonsense mutations.METHODS: The study sample comprised 1090 patients with genetically confirmed mutations. Patients were categorized into 5 groups, depending on mutation type and location: missense not located in the high-risk cytoplasmic loop (c-loop) (n = 698), which is used as reference; missense c-loop (n = 192); stop-codon (n = 67); frameshift (n = 39); and others (n = 94). The primary outcome was a composite end point of syncope, aborted cardiac arrest, and long QT syndrome-related death (cardiac events). Outcomes were evaluated using the multivariate Cox proportional hazards regression analysis. Standard patch clamp techniques were used.RESULTS: Compared to patients with missense non-c-loop mutations, the risk of cardiac events was reduced significantly in patients with stop-codon mutations (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.34-0.96; P = .035), but not in patients with frameshift mutations (HR 1.01; 95% CI 0.58-1.77; P = .97). Our data suggest that currents of the most common stop-codon mutant channel (Q530X) were larger than those of haploinsufficient channels (wild type: 42 ± 6 pA/pF, n = 20; Q530X+wild type: 79 ± 14 pA/pF, n = 20; P < .05) and voltage dependence of activation was altered.CONCLUSION: Stop-codon mutations are associated with a lower risk of cardiac events in patients with LQT1, while frameshift mutations are associated with the same risk as the majority of the missense mutations. Our data indicate functional differences between these previously consider
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- 2016
18. Electrocardiographic measurements of the QT interval during embryonic development in fertilized chicken eggs
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Bhuiyan, Tanveer A., Sevcencu, Cristian, Struijk, Johannes J., Kanters, Jorgen K., Graff, Claus, Bhuiyan, Tanveer A., Sevcencu, Cristian, Struijk, Johannes J., Kanters, Jorgen K., and Graff, Claus
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The fertilized chicken egg (embryonic chicken) shares the basic mechanism of electrophysiology and ionic currents with mammalian hearts. However, little is known about the cardiac repolarization process during embryo growth. We examined if the electrocardiographic QT interval was dependent on the stage of embryonic development. ECGs were recorded from 4 fertilized chicken eggs for 6 days (day 13 to day 18). Eggs were kept in an incubator with a temperature of 37.4°C. Chronic electrodes were implanted and a 5-minute ECG was recorded each day. Three measurements were made in noise free segments: Heart rate, QT interval, and the Fridericia corrected QT interval (QTcF), and an average value was calculated. The QTcF interval decreased during embryo development. On day 18, QTcF was shorter than QTcF on day 13: 341 ms (95% CI: 332 ms to 349 ms) versus 417 (95% CI: 325 ms to 509 ms), p=0.037. In fertilized chicken eggs, the repolarization process changes during development. This property makes the chicken embryo an interesting model for the study of drug effects on the QT interval at different stages of embryo development.
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- 2016
19. Long QT syndrome — a cause of sudden death
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Dembić, Maja, Brusich, Sandro, Louise Hedley, Paula, De Villiers, Carin Pamela, Čubranić, Zlatko, Kanters, Jorgen Kim, Zaputović, Luka, and Christiansen, Michael
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BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina ,sindrom dugog QT intervala ,aritmije srca ,iznenadna srčana smrt ,long QT sindrome ,iznenadna srcana smrt ,sudden cardiac death ,arrhythmia ,BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine - Abstract
Sindrom dugog QT intervala (LQTS) je primarni aritmijski poremeÊaj koji moæe dovesti do pojave malignih ventrikularnih aritmija tipa torsades de pointes (TdP) i iznenadne srËane smrti. Obiljeæja u elektrokardiogramu (EKG) ukljuËuju produljenje korigiranog QT intervala i abnormalnosti T-vala. Do danas identificirana genetska osnova za LQTS ukljuËuje trinaest podloænih gena: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, i KCNJ5. NajËeπÊi genotip su mutacije KCNQ1 te gotovo polovica pacijenata ima tu vrstu mutacije. Navedeni geni kodiraju ionske kanale i regulatorne proteine koji su ukljuËeni u modulaciju struja srËanog akcijskog potencijala. SteËeni oblici LQTS-a mogu takoer biti uzrokovani genetskim mutacijama, u tim sluËajevima nositelji mutacija razvijaju aritmije iskljuËivo u odreenim uvjetima (npr. uporaba odreenih lijekova). Trenutna terapija ukljuËuje primjenu beta-blokatora, ugradnju implantabilnog kardioverter defibrilatora (ICD) te simpatiËku denervaciju srca. LQTS mutacije povezane su s iznenadnom srËanom smrti kod mladih i veoma mladih; a post-mortem genetska testiranja LQTS gena mogu biti korisna kod procjene uzroka iznenadne neobjaπnjive smrti (sudden unexplained death). Kaskadni probir koristan je za identificiranje asimptomatskih Ëlanova obitelji koji mogu biti pod poveÊanim rizikom od iznenadne smrti. U ovom preglednom Ëlanku prikazali smo gene povezane s LQTS-om zajedno s opisom povezanih patofizioloπkih mehanizama., Long QT syndrome (LQTS) is a primary arrhythmic disorder that may lead to the precipitation of torsades de pointes (TdP) and sudden death. Electrocardiogram (ECG) features include prolongation of the corrected QT interval and T-wave abnormalities. The genetic basis of LQTS identified to date includes thirteen susceptibility genes: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, and KCNJ5. Mutations in KCNQ1 are by far the most frequent genotype with nearly half of the patients carrying KCNQ1 mutations. These genes code for ion channels and regulatory proteins that are involved in the modulation of the currents of the cardiac action potential (AP). Acquired forms of LQTS may also have underlying genetic mutations, in these cases mutation carriers develop arrhythmias only under certain conditions (e. g. use of certain medications). Current therapies include use of beta-blockers, implantable cardioverter defibrillators (ICD) and left cardiac sympathetic denervation. LQTS mutations have been associated with sudden death in the young and very young; and postmortem genetic testing in LQTS genes can be useful when assessing the cause of a sudden unexplained death. Cascade screening is also useful to identify asymptomatic family members that may be at risk of sudden death. Here we have reviewed the genes associated with LQTS along with the description of the related pathophysiological mechanisms
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- 2012
20. In Silico Cardiac Risk Assessment in Patients With Long QT Syndrome
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Hoefen, Ryan, primary, Reumann, Matthias, additional, Goldenberg, Ilan, additional, Moss, Arthur J., additional, O-Uchi, Jin, additional, Gu, Yiping, additional, McNitt, Scott, additional, Zareba, Wojciech, additional, Jons, Christian, additional, Kanters, Jorgen K., additional, Platonov, Pyotr G., additional, Shimizu, Wataru, additional, Wilde, Arthur A.M., additional, Rice, John Jeremy, additional, and Lopes, Coeli M., additional
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- 2012
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21. Mutations in Cytoplasmic Loops of the KCNQ1 Channel and the Risk of Life-Threatening Events
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Barsheshet, Alon, primary, Goldenberg, Ilan, additional, O-Uchi, Jin, additional, Moss, Arthur J., additional, Jons, Christian, additional, Shimizu, Wataru, additional, Wilde, Arthur A., additional, McNitt, Scott, additional, Peterson, Derick R., additional, Zareba, Wojciech, additional, Robinson, Jennifer L., additional, Ackerman, Michael J., additional, Cypress, Michael, additional, Gray, Daniel A., additional, Hofman, Nynke, additional, Kanters, Jorgen K., additional, Kaufman, Elizabeth S., additional, Platonov, Pyotr G., additional, Qi, Ming, additional, Towbin, Jeffrey A., additional, Vincent, G. Michael, additional, and Lopes, Coeli M., additional
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- 2012
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22. A New Stochastic Model to Interpret Heart Rate Variability
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Lu, Sheng, Kanters, Jorgen, Chon, Ki H., Lu, Sheng, Kanters, Jorgen, and Chon, Ki H.
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While ample evidence suggests heart rate control is nonlinear, controversies abound as to whether or not heart rate dynamics involve deterministic chaos. Our analysis, based on the method developed, suggests that heart rate variability can be characterized by bounded random processes and the degree of boundedness becomes tighter with disease conditions such as myocardial infarction.
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- 2003
23. LOCAL VOLTAGE POTENTIALS ARE PREREQUISITES FOR OUTFLOW TRACT ECTOPY
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Thomsen, Poul Erik Bloch, primary, Johannessen, Arne, additional, Jons, Christian, additional, Kanters, Jorgen K., additional, Saermark, Knud, additional, Antzelevitch, Charles, additional, and Sogaard, Peter, additional
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- 2010
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24. A stochastic nonlinear autoregressive algorithm reflects nonlinear dynamics of heart-rate fluctuations
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Armoundas, Antonis A., Ju, Kihwan, Iyengar, Nikhil, Kanters, Jorgen K., Saul, Philip J., Cohen, Richard J., Chon, Ki H., Armoundas, Antonis A., Ju, Kihwan, Iyengar, Nikhil, Kanters, Jorgen K., Saul, Philip J., Cohen, Richard J., and Chon, Ki H.
- Abstract
A new computational algorithm to quantify nonlinear heart-rate dynamics was developed. The term stochastic nonlinear autoregressive (SNAR) model was coined to emphasize that the method models both the deterministic and the stochastic components of the system. Finally, the applicability and reliability of the SNAR algorithm to predict the outcome of cardiac electrophysiologic study (EPS) were demonstrated.
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- 2002
25. Beat-to-Beat QT Dynamics in Healthy Subjects
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Jensen, Berit T., primary, Larroude, Charlotte E., additional, Rasmussen, Lars P., additional, Holstein-Rathlou, Niels-Henrik, additional, Hojgaard, Michael V., additional, Agner, Erik, additional, and Kanters, Jorgen K., additional
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- 2004
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26. Discovery of novel heart rate-associated loci using the Exome Chip
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van den Berg, Marten E., Warren, Helen R., Cabrera, Claudia P., Verweij, Niek, Mifsud, Borbala, Haessler, Jeffrey, Bihlmeyer, Nathan A., Fu, Yi-Ping, Weiss, Stefan, Lin, Henry J., Grarup, Niels, Li-Gao, Ruifang, Pistis, Giorgio, Shah, Nabi, Brody, Jennifer A., Müller-Nurasyid, Martina, Lin, Honghuang, Mei, Hao, Smith, Albert V., Lyytikäinen, Leo-Pekka, Hall, Leanne M., van Setten, Jessica, Trompet, Stella, Prins, Bram P., Isaacs, Aaron, Radmanesh, Farid, Marten, Jonathan, Entwistle, Aiman, Kors, Jan A., Silva, Claudia T., Alonso, Alvaro, Bis, Joshua C., de Boer, Rudolf, de Haan, Hugoline G., de Mutsert, Renée, Dedoussis, George, Dominiczak, Anna F., Doney, Alex S. F., Ellinor, Patrick T., Eppinga, Ruben N., Felix, Stephan B., Guo, Xiuqing, Hagemeijer, Yanick, Hansen, Torben, Harris, Tamara B., Heckbert, Susan R., Huang, Paul L., Hwang, Shih-Jen, Kähönen, Mika, Kanters, Jørgen K., Kolcic, Ivana, Launer, Lenore J., Li, Man, Yao, Jie, Linneberg, Allan, Liu, Simin, Macfarlane, Peter W., Mangino, Massimo, Morris, Andrew D., Mulas, Antonella, Murray, Alison D., Nelson, Christopher P., Orrú, Marco, Padmanabhan, Sandosh, Peters, Annette, Porteous, David J., Poulter, Neil, Psaty, Bruce M., Qi, Lihong, Raitakari, Olli T., Rivadeneira, Fernando, Roselli, Carolina, Rudan, Igor, Sattar, Naveed, Sever, Peter, Sinner, Moritz F., Soliman, Elsayed Z., Spector, Timothy D., Stanton, Alice V., Stirrups, Kathleen E., Taylor, Kent D., Tobin, Martin D., Uitterlinden, André, Vaartjes, Ilonca, Hoes, Arno W., van der Meer, Peter, Völker, Uwe, Waldenberger, Melanie, Xie, Zhijun, Zoledziewska, Magdalena, Tinker, Andrew, Polasek, Ozren, Rosand, Jonathan, Jamshidi, Yalda, van Duijn, Cornelia M., Zeggini, Eleftheria, Jukema, J. Wouter, Asselbergs, Folkert W., Samani, Nilesh J., Lehtimäki, Terho, Gudnason, Vilmundur, Wilson, James, Lubitz, Steven A., Kääb, Stefan, Sotoodehnia, Nona, Caulfield, Mark J., Palmer, Colin N. A., Sanna, Serena, Mook-Kanamori, Dennis O., Deloukas, Panos, Pedersen, Oluf, Rotter, Jerome I., Dörr, Marcus, O'Donnell, Chris J., Hayward, Caroline, Arking, Dan E., Kooperberg, Charles, van der Harst, Pim, Eijgelsheim, Mark, Stricker, Bruno H., and Munroe, Patricia B.
- 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.
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- 2017
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27. Dynamics of spectral components of heart rate variability...
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Hojgaard, Michael V., Holstein-Rathlou, Niels-Herik, Agner, Erik, and Kanters, Jorgen K.
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SYMPATHETIC nervous system ,PHYSIOLOGY - Abstract
Examines whether absolute and normalized power and the low frequency-to-high frequency ratio derived from heart rate variability (HRV) power spectrum could detect shifts in autonomic balance in a low sympathetic nervous tone. Details on heart rate variability; Methodology; Discussion of results.
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- 1998
28. Abstract 13222: Genetic Variants Close to NKX2-5and MYH6Are Associated With AV Nodal Reentry Tachycardia in First Genome-Wide Association Study
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Andreasen, Laura, Ahlberg, Gustav, Lundegaard, Pia Rengtved, Ægisdottir, Hildur, Hartmann, Jacob Peter, Paludan-Mueller, Christian, Hadji-Turdeghal, Katra, Ghouse, Jonas, Pehrson, Steen, Jensen, Henrik, Riahi, Sam, Hansen, Jim, Sandgaard, Niels, Haunso, stig, Kanters, Jorgen, Ellervik, Christina, Bundgaard, Henning, Ullum, Henrik, Holm, Hilma, Arnar, David, Svendsen, Jesper Hastrup, and Olesen, Morten
- Abstract
Introduction:AV nodal re-entry tachycardia (AVNRT) is the most common type of paroxysmal supraventricular tachycardia. At present, the underlying etiology of AVNRT is unclear.Hypothesis:In a genome-wide association study (GWAS), we aimed to identify common genetic variants associated with AVNRT.Methods:We performed a GWAS meta-analysis of Danish patients diagnosed with AVNRT verified by invasive electrophysiological study. An Icelandic population of AVNRT patients was used for replication. We performed conditional analysis by adjusting our analysis for atrial fibrillation (AF) genetics and transcriptome-wide analyses (TWAS) to assess associations between gene expression and AVNRT. Electrophysiological consequences were investigated in CRISPR-Cas9 modified zebrafish.Results:A total of 1,515 AVNRT patients and 38,428 controls were available for meta-analysis. Two genetic loci associated with AVNRT; at chromosome 5q35.1, close to the NKX2-5gene (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.38-1.58, P = 2.6 х 10-13), and at 14q11.2 in the MYH6gene (OR 1.26, 95% CI 1.18-1.34, P = 2.3 х 10-8). We found similar effect sizes and direction of effect for both loci in the Icelandic AVNRT cohort. Using conditional analyses, we found that these loci were associated with AVNRT independent of AF. Analyses of loss of Nkx2-5 zebrafish showed no difference with regards to electrocardiographic parameters and transmission electron microscopy of atrial tissue compared with wildtype.Conclusion:This is, to our knowledge, the first GWAS on AVNRT. We identified two genetic loci that associated with AVNRT.
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- 2021
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29. Abstract 12381: Clinical Implications of SCN5Aand SCN10ALoss of Function Variants in 169,610 Exomes Representing the General Population
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Paludan-Mueller, Christian, Larsen, Simon, Ahlberg, Gustav, Andreasen, Laura, Svendsen, Jesper Hastrup H, Kanters, Jorgen K, and Olesen, Morten S
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Background:Genetic variation in the genes SCN5Aand SCN10Ahas previously been associated with cardiac disease and conduction velocity through genome-wide association studies (GWAS) and rare variant analyses. The two neighboring genes constitute the much-investigated SCN5A-SCN10Alocus, and it has been challenging to determine the region’s function as GWAS often identifies variants in non-coding regions. The cardiac function of SCN5Ais well established whereas the role of SCN10Ain cardiac conduction and disease remains disputed. The study focuses on SCN10Awhile SCN5Awas included for comparative analyses.Methods and Results:We accessed the UK Biobank database, which contains data on >500,000 individuals. The recent exome release provides whole-exome sequencing data on 169,610 unrelated European individuals while resting ECGs are available on 44,987 individuals. We identified 668 individuals harboring LOF-variants (leading to early stop codon, frameshift or splice site disruption) in SCN10Aand SCN5Awith a MAF <1%. Among the 668 individuals, 543 individuals carried SCN10Avariants, whereas 125 individuals held a variant in SCN5A. There were 88 and 37 different variants in SCN10Aand SCN5A, respectively. From these individuals, we obtained 69 ECGs in sinus rhythm and 55 of these were recorded on individuals with a SCN10ALOF-variant and 14 ECGs were recorded on individuals with a SCN5ALOF-variant. Linear regression analyses established an association between SCN5ALOF-variants and prolongation of the PR-interval as carrying a variant corresponds to an average PR prolongation of 25.1 milliseconds (P = 0.001). There were no statistically significant alterations among other ECG parameters. Furthermore, we could not determine correlations of ECG parameters for SCN10ALOF-variants. A burden test on SCN10Aand SCN5ALOF-variants could not establish a relationship with atrial fibrillation (P = 0.26 and P = 0.41, respectively) and heart failure (P = 0.92 and P = 0.17, respectively). Remaining possible disease associations could not be properly established due to low number of cases.Conclusion:These findings confirm the significance of SCN5Ain cardiac conduction while questioning the function of SCN10Ain human cardiac conduction and disease.
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- 2021
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