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5. Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

Author

Bergeman, Auke, Lieve, Krystien, Kallas, Dania, Bos, J, Rosés I Noguer, Ferran, Denjoy, Isabelle, Zorio, Esther, Kammeraad, Janneke, Peltenburg, Puck, Tobert, Katie, Aiba, Takeshi, Atallah, Joseph, Drago, Fabrizio, Batra, Anjan, Brugada, Ramon, Borggrefe, Martin, Clur, Sally-Ann, Cox, Moniek, Davis, Andrew, Dhillon, Santokh, Etheridge, Susan, Fischbach, Peter, Franciosi, Sonia, Haugaa, Kristina, Horie, Minoru, Johnsrude, Christopher, Kane, Austin, Krause, Ulrich, Kwok, Sit-Yee, LaPage, Martin, Ohno, Seiko, Probst, Vincent, Roberts, Jason, Robyns, Tomas, Sacher, Frederic, Semsarian, Christopher, Skinner, Jonathan, Swan, Heikki, Tavacova, Terezia, Tisma-Dupanovic, Svjetlana, Tfelt-Hansen, Jacob, Yap, Sing-Chien, Kannankeril, Prince, Leenhardt, Antoine, Till, Janice, Sanatani, Shubhayan, Tanck, Michael, Ackerman, Michael, Wilde, Arthur, and van der Werf, Christian

Subjects
catecholaminergic polymorphic ventricular tachycardia, sudden cardiac death, ventricular arrhythmias, Female, Humans, Adolescent, Male, Flecainide, Incidence, Cross-Over Studies, Tachycardia, Ventricular, Adrenergic beta-Antagonists, Defibrillators, Implantable, Death, Sudden, Cardiac
Abstract

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P

Published
2023

17. Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve KCNH2-LQTS Variant Classification and Cardiac Event Risk Stratification

Author

O’Neill, Matthew J., Ng, Chai-Ann, Aizawa, Takanori, Sala, Luca, Bains, Sahej, Winbo, Annika, Ullah, Rizwan, Shen, Qianyi, Tan, Chek-Ying, Kozek, Krystian, Vanags, Loren R., Mitchell, Devyn W., Shen, Alex, Wada, Yuko, Kashiwa, Asami, Crotti, Lia, Dagradi, Federica, Musu, Giulia, Spazzolini, Carla, Neves, Raquel, Bos, J. Martijn, Giudicessi, John R., Bledsoe, Xavier, Gamazon, Eric R., Lancaster, Megan C., Glazer, Andrew M., Knollmann, Bjorn C., Roden, Dan M., Weile, Jochen, Roth, Frederick, Salem, Joe-Elie, Earle, Nikki, Stiles, Rachael, Agee, Taylor, Johnson, Christopher N., Horie, Minoru, Skinner, Jonathan R., Ackerman, Michael J., Schwartz, Peter J., Ohno, Seiko, Vandenberg, Jamie I., and Kroncke, Brett M.

Published
2024
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18. An international multicenter cohort study on implantable cardioverter-defibrillators for the treatment of symptomatic children with catecholaminergic polymorphic ventricular tachycardia

Author

Lamba, Avani, Roston, Thomas M., Peltenburg, Puck J., Kallas, Dania, Franciosi, Sonia, Lieve, Krystien V.V., Kannankeril, Prince J., Horie, Minoru, Ohno, Seiko, Brugada, Ramon, Aiba, Takeshi, Fischbach, Peter, Knight, Linda, Till, Jan, Kwok, Sit-Yee, Probst, Vincent, Backhoff, David, LaPage, Martin J., Batra, Anjan S., Drago, Fabrizio, Haugaa, Kristina, Krahn, Andrew D., Robyns, Tomas, Swan, Heikki, Tavacova, Terezia, van der Werf, Christian, Atallah, Joseph, Borggrefe, Martin, Rudic, Boris, Sarquella-Brugada, Georgia, Chorin, Ehud, Hill, Allison, Kammeraad, Janneke, Kamp, Anna, Law, Ian, Perry, James, Roberts, Jason D., Tisma-Dupanovic, Svjetlana, Semsarian, Christopher, Skinner, Jonathan R., Tfelt-Hansen, Jacob, Denjoy, Isabelle, Leenhardt, Antoine, Schwartz, Peter J., Ackerman, Michael J., Blom, Nico A., Wilde, Arthur A.M., and Sanatani, Shubhayan

Published
2024
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24. An International Multicenter Evaluation of Type 5 Long QT Syndrome

Author

Roberts, Jason D, Asaki, S Yukiko, Mazzanti, Andrea, Bos, J Martijn, Tuleta, Izabela, Muir, Alison R, Crotti, Lia, Krahn, Andrew D, Kutyifa, Valentina, Shoemaker, M Benjamin, Johnsrude, Christopher L, Aiba, Takeshi, Marcondes, Luciana, Baban, Anwar, Udupa, Sharmila, Dechert, Brynn, Fischbach, Peter, Knight, Linda M, Vittinghoff, Eric, Kukavica, Deni, Stallmeyer, Birgit, Giudicessi, John R, Spazzolini, Carla, Shimamoto, Keiko, Tadros, Rafik, Cadrin-Tourigny, Julia, Duff, Henry J, Simpson, Christopher S, Roston, Thomas M, Wijeyeratne, Yanushi D, El Hajjaji, Imane, Yousif, Maisoon D, Gula, Lorne J, Leong-Sit, Peter, Chavali, Nikhil, Landstrom, Andrew P, Marcus, Gregory M, Dittmann, Sven, Wilde, Arthur AM, Behr, Elijah R, Tfelt-Hansen, Jacob, Scheinman, Melvin M, Perez, Marco V, Kaski, Juan Pablo, Gow, Robert M, Drago, Fabrizio, Aziz, Peter F, Abrams, Dominic J, Gollob, Michael H, Skinner, Jonathan R, Shimizu, Wataru, Kaufman, Elizabeth S, Roden, Dan M, Zareba, Wojciech, Schwartz, Peter J, Schulze-Bahr, Eric, Etheridge, Susan P, Priori, Silvia G, and Ackerman, Michael J

Subjects
Genetics, Cardiovascular, Clinical Trials and Supportive Activities, Heart Disease, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Death, Sudden, Cardiac, Electric Countershock, Electrocardiography, Female, Heart Arrest, Humans, Long QT Syndrome, Male, Middle Aged, Penetrance, Potassium Channels, Voltage-Gated, Registries, arrhythmia, genetics, long QT syndrome, penetrance, sudden cardiac death, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundInsight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration.MethodsPatients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death.ResultsA total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P

Published
2020

38. The Economics of Aging

Author

Skinner, Jonathan

Subjects
Baby boom generation -- Forecasts and trends, Market trend/market analysis, Business, general, Business, Economics
Abstract

When the NBER's Program on the Economics of Aging began in 1986 under the direction of David Wise, the baby-boom generation was between the ages of 22 and 40. Long-run [...]

Published
2022

44. 2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families

Author

Stiles, Martin K., Wilde, Arthur A.M., Abrams, Dominic J., Ackerman, Michael J., Albert, Christine M., Behr, Elijah R., Chugh, Sumeet S., Cornel, Martina C., Gardner, Karen, Ingles, Jodie, James, Cynthia A., Jimmy Juang, Jyh-Ming, Kääb, Stefan, Kaufman, Elizabeth S., Krahn, Andrew D., Lubitz, Steven A., MacLeod, Heather, Morillo, Carlos A., Nademanee, Koonlawee, Probst, Vincent, Saarel, Elizabeth V., Sacilotto, Luciana, Semsarian, Christopher, Sheppard, Mary N., Shimizu, Wataru, Skinner, Jonathan R., Tfelt-Hansen, Jacob, and Wang, Dao Wu

Published
2021
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48. Loss of ventricular preexcitation during noninvasive testing does not exclude high-risk accessory pathways: A multicenter study of WPW in children

Author

Escudero, Carolina A., Ceresnak, Scott R., Collins, Kathryn K., Pass, Robert H., Aziz, Peter F., Blaufox, Andrew D., Ortega, Michel Cabrera, Cannon, Bryan C., Cohen, Mitchell I., Dechert, Brynn E., Dubin, Anne M., Motonaga, Kara S., Epstein, Michael R., Erickson, Christopher C., Fishberger, Steven B., Gates, Gregory J., Capone, Christine A., Nappo, Lynn, Kertesz, Naomi J., Kim, Jeffrey J., Valdes, Santiago O., Kubuš, Peter, Law, Ian H., Maldonado, Jennifer, Moore, Jeremy P., Perry, James C., Sanatani, Shubhayan, Seslar, Stephen P., Shetty, Ira, Zimmerman, Frank J., Skinner, Jonathan R., Marcondes, Luciana, Stephenson, Elizabeth A., Asakai, Hiroko, Tanel, Ronn E., Uzun, Orhan, Etheridge, Susan P., and Janson, Christopher M.

Published
2020
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