Citations 2
Clinical Management of Brugada Syndrome: Commentary From the Experts
Cutler, Michael J. , Eckhardt, Lee L. , Kaufman, Elizabeth S. , Arbelo, Elena , Behr, Elijah R. , Brugada, Pedro , Crotti, Lia , Asmundis, Carlo de , Horie, Minoru , Huang, David T. , Lubitz, Steven A. , Mackall, Judith A. , Roden, Dan M. , Sacher, Frédéric , Shoemaker, Benjamin, Sy, Raymond W. , Watanabe, Atsuyuki , Wilde, Arthur A.M. , Cerrone, Marina , Crotti, Lia , deAsmundis, Carlo , Gollob, Michael H , Horie, Minoru , Huang, David T , Krahn, Andrew D , London, Barry , Lubitz, Steven A , Mackall, Judith A , Nademanee, Koonlawee , Perez, Marco V , Probst, Vincent , Roden, Dan M. , Sacher, Frederic , Sarquella-Brugada, Georgia , Scheinman, Melvin M , Shimizu, Wataru , Shoemaker, M Benjamin , Sy, Raymond W , Wilde, Arthur A M , Behr, Elijah Raphael , Eckhardt, Lee L , Arbelo, Elena , Cerrone, Marina , Gollob, Michael H. , Krahn, Andrew D. , London, Barry , Nademanee, Koonlawee , Pérez, Marco
Circulation: Arrhythmia and Electrophysiology | December 15, 2023 | Volume: 17 | Issue: 1 | Pages: No page available
Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.
Arrhythmia Variant Associations and Reclassifications in the eMERGE-III Sequencing Study
Glazer, Andrew M. , Davogustto, Giovanni , Shaffer, Christian M., Desai, Reshma R. , Farber‐Eger, Eric , Dikilitas, Ozan , Shang, Ning , Muhammad, Ayesha , Shaffer, Lauren Lee, Kalash, Olivia R., Bland, Harris T. , Yoneda, Zachary T. , Mitchell, Devyn , Kroncke, Brett M. , Jarvik, Gail P. , Gordon, Allan , Larson, Eric B. , Manolio, Teri A. , Luo, Jonathan Z. , Schaid, Daniel J. , Namjou, Bahram , Singhal, Ashutosh , Liu, Cong , Ralston, James D. , Leppig, Kathleen A. , Håkonarson, Håkon , Sleiman, Patrick , Sohn, Sunghwan , Network, the eMERGE, Denny, Joshua C. , Wei, Wei‐Qi, Shoemaker, M. Benjamin , Roden, Dan M. , Ralston, James D. , Farber-Eger, Eric H , Dikilitas, Ozan , Mosley, Jonathan D , Van Driest, Sara L , Wells, Quinn S , Wada, Yuko , Yoneda, Zachary T , Kroncke, Brett M , Kullo, Iftikhar J , Jarvik, Gail P , Gordon, Adam S , Manolio, Teri A , Mirshahi, Tooraj , Schaid, Daniel, Alsaied, Tarek , Hripcsak, George , McNally, Elizabeth M , Sohn, Sunghwan , Glessner, Joseph , Wei, Wei-Qi , George, Alfred L , Shoemaker, M Benjamin , Roden, Dan M. , Hakonarson, Hakon , Denny, Joshua C , Bland, Sarah T , Liu, Cong , Glazer, Andrew M , Vanoye, Carlos G. , Pacheco, Jennifer A. , Yang, Tao , Driest, Sara L. Van , Wells, Quinn S. , Wada, Yuko , Kullo, Iftikhar J. , Singh, Rajbir , Weng, Chunhua , McNally, Elizabeth M. , Chung, Wendy K. , Carrell, David , Network, the eMERGE, George, Alfred L.
Circulation | December 21, 2021 | Volume: 145 | Issue: 12 | Pages: 877-891
10.1161/circulationaha.121.055562
Background: Sequencing Mendelian arrhythmia genes in individuals without an indication for arrhythmia genetic testing can identify carriers of pathogenic or likely pathogenic (P/LP) variants. However, the extent to which these variants are associated with clinically meaningful phenotypes before or after return of variant results is unclear. In addition, the majority of discovered variants are currently classified as variants of uncertain significance, limiting clinical actionability. Methods: The eMERGE-III study (Electronic Medical Records and Genomics Phase III) is a multicenter prospective cohort that included 21 846 participants without previous indication for cardiac genetic testing. Participants were sequenced for 109 Mendelian disease genes, including 10 linked to arrhythmia syndromes. Variant carriers were assessed with electronic health record–derived phenotypes and follow-up clinical examination. Selected variants of uncertain significance (n=50) were characterized in vitro with automated electrophysiology experiments in HEK293 cells. Results: As previously reported, 3.0% of participants had P/LP variants in the 109 genes. Herein, we report 120 participants (0.6%) with P/LP arrhythmia variants. Compared with noncarriers, arrhythmia P/LP carriers had a significantly higher burden of arrhythmia phenotypes in their electronic health records. Fifty-four participants had variant results returned. Nineteen of these 54 participants had inherited arrhythmia syndrome diagnoses (primarily long-QT syndrome), and 12 of these 19 diagnoses were made only after variant results were returned (0.05%). After in vitro functional evaluation of 50 variants of uncertain significance, we reclassified 11 variants: 3 to likely benign and 8 to P/LP. Conclusions: Genome sequencing in a large population without indication for arrhythmia genetic testing identified phenotype-positive carriers of variants in congenital arrhythmia syndrome disease genes. As the genomes of large numbers of people are sequenced, the disease risk from rare variants in arrhythmia genes can be assessed by integrating genomic screening, electronic health record phenotypes, and in vitro functional studies. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier; NCT03394859.