Cardiac phenotype in ATP1A3-related syndromes
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/2686 |
Resumo: | Objective: To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. Methods: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/-) to determine the sequence of events in seizure-related cardiac death. Results: Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. Conclusions: We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator. |
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Cardiac phenotype in ATP1A3-related syndromesObjective: To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. Methods: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/-) to determine the sequence of events in seizure-related cardiac death. Results: Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. Conclusions: We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.Wolters Kluwer HealthRepositório Científico do Centro Hospitalar Universitário de Santo AntónioBalestrini, SimonaMikati, Mohamad A.Álvarez-García-Rovés, ReyesCarboni, MichaelHunanyan, Arsen S.Kherallah, BassilMcLean, MelissaPrange, LyndseyDe Grandis, ElisaGagliardi, AlessandraPisciotta, LiviaStagnaro, MichelaVeneselli, EdvigeCampistol, JaumeFons, CarmenPias-Peleteiro, LeticiaBrashear, AllisonMiller, CharlotteSamões, RaquelBrankovic, VesnaPadiath, Quasar S.Potic, AnaPilch, JacekVezyroglou, AikateriniBye, Ann M.E.Davis, Andrew M.Ryan, Monique M.Semsarian, ChristopherHollingsworth, GeorginaScheffer, Ingrid E.Granata, TizianaNardocci, NardoRagona, FrancescaArzimanoglou, AlexisPanagiotakaki, EleniCarrilho, InêsZucca, ClaudioNovy, JanDzieżyc, KarolinaParowicz, MarekMazurkiewicz-Bełdzińska, MariaWeckhuysen, SarahPons, RoserGroppa, SergiuSinden, Daniel S.Pitt, Geoffrey S.Tinker, AndrewAshworth, MichaelMichalak, ZuzannaThom, MariaCross, J. HelenVavassori, RosariaKaski, Juan P.Sisodiya, Sanjay M.2022-06-30T11:02:01Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2686engBalestrini S, Mikati MA, Álvarez-García-Rovés R, et al. Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study. Neurology. 2020;95(21):e2866-e2879. doi:10.1212/WNL.00000000000107940028-387810.1212/WNL.0000000000010794info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T11:01:41Zoai:repositorio.chporto.pt:10400.16/2686Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:52.910639Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cardiac phenotype in ATP1A3-related syndromes |
title |
Cardiac phenotype in ATP1A3-related syndromes |
spellingShingle |
Cardiac phenotype in ATP1A3-related syndromes Balestrini, Simona |
title_short |
Cardiac phenotype in ATP1A3-related syndromes |
title_full |
Cardiac phenotype in ATP1A3-related syndromes |
title_fullStr |
Cardiac phenotype in ATP1A3-related syndromes |
title_full_unstemmed |
Cardiac phenotype in ATP1A3-related syndromes |
title_sort |
Cardiac phenotype in ATP1A3-related syndromes |
author |
Balestrini, Simona |
author_facet |
Balestrini, Simona Mikati, Mohamad A. Álvarez-García-Rovés, Reyes Carboni, Michael Hunanyan, Arsen S. Kherallah, Bassil McLean, Melissa Prange, Lyndsey De Grandis, Elisa Gagliardi, Alessandra Pisciotta, Livia Stagnaro, Michela Veneselli, Edvige Campistol, Jaume Fons, Carmen Pias-Peleteiro, Leticia Brashear, Allison Miller, Charlotte Samões, Raquel Brankovic, Vesna Padiath, Quasar S. Potic, Ana Pilch, Jacek Vezyroglou, Aikaterini Bye, Ann M.E. Davis, Andrew M. Ryan, Monique M. Semsarian, Christopher Hollingsworth, Georgina Scheffer, Ingrid E. Granata, Tiziana Nardocci, Nardo Ragona, Francesca Arzimanoglou, Alexis Panagiotakaki, Eleni Carrilho, Inês Zucca, Claudio Novy, Jan Dzieżyc, Karolina Parowicz, Marek Mazurkiewicz-Bełdzińska, Maria Weckhuysen, Sarah Pons, Roser Groppa, Sergiu Sinden, Daniel S. Pitt, Geoffrey S. Tinker, Andrew Ashworth, Michael Michalak, Zuzanna Thom, Maria Cross, J. Helen Vavassori, Rosaria Kaski, Juan P. Sisodiya, Sanjay M. |
author_role |
author |
author2 |
Mikati, Mohamad A. Álvarez-García-Rovés, Reyes Carboni, Michael Hunanyan, Arsen S. Kherallah, Bassil McLean, Melissa Prange, Lyndsey De Grandis, Elisa Gagliardi, Alessandra Pisciotta, Livia Stagnaro, Michela Veneselli, Edvige Campistol, Jaume Fons, Carmen Pias-Peleteiro, Leticia Brashear, Allison Miller, Charlotte Samões, Raquel Brankovic, Vesna Padiath, Quasar S. Potic, Ana Pilch, Jacek Vezyroglou, Aikaterini Bye, Ann M.E. Davis, Andrew M. Ryan, Monique M. Semsarian, Christopher Hollingsworth, Georgina Scheffer, Ingrid E. Granata, Tiziana Nardocci, Nardo Ragona, Francesca Arzimanoglou, Alexis Panagiotakaki, Eleni Carrilho, Inês Zucca, Claudio Novy, Jan Dzieżyc, Karolina Parowicz, Marek Mazurkiewicz-Bełdzińska, Maria Weckhuysen, Sarah Pons, Roser Groppa, Sergiu Sinden, Daniel S. Pitt, Geoffrey S. Tinker, Andrew Ashworth, Michael Michalak, Zuzanna Thom, Maria Cross, J. Helen Vavassori, Rosaria Kaski, Juan P. Sisodiya, Sanjay M. |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
dc.contributor.author.fl_str_mv |
Balestrini, Simona Mikati, Mohamad A. Álvarez-García-Rovés, Reyes Carboni, Michael Hunanyan, Arsen S. Kherallah, Bassil McLean, Melissa Prange, Lyndsey De Grandis, Elisa Gagliardi, Alessandra Pisciotta, Livia Stagnaro, Michela Veneselli, Edvige Campistol, Jaume Fons, Carmen Pias-Peleteiro, Leticia Brashear, Allison Miller, Charlotte Samões, Raquel Brankovic, Vesna Padiath, Quasar S. Potic, Ana Pilch, Jacek Vezyroglou, Aikaterini Bye, Ann M.E. Davis, Andrew M. Ryan, Monique M. Semsarian, Christopher Hollingsworth, Georgina Scheffer, Ingrid E. Granata, Tiziana Nardocci, Nardo Ragona, Francesca Arzimanoglou, Alexis Panagiotakaki, Eleni Carrilho, Inês Zucca, Claudio Novy, Jan Dzieżyc, Karolina Parowicz, Marek Mazurkiewicz-Bełdzińska, Maria Weckhuysen, Sarah Pons, Roser Groppa, Sergiu Sinden, Daniel S. Pitt, Geoffrey S. Tinker, Andrew Ashworth, Michael Michalak, Zuzanna Thom, Maria Cross, J. Helen Vavassori, Rosaria Kaski, Juan P. Sisodiya, Sanjay M. |
description |
Objective: To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. Methods: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/-) to determine the sequence of events in seizure-related cardiac death. Results: Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. Conclusions: We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2022-06-30T11:02:01Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.16/2686 |
url |
http://hdl.handle.net/10400.16/2686 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Balestrini S, Mikati MA, Álvarez-García-Rovés R, et al. Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study. Neurology. 2020;95(21):e2866-e2879. doi:10.1212/WNL.0000000000010794 0028-3878 10.1212/WNL.0000000000010794 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wolters Kluwer Health |
publisher.none.fl_str_mv |
Wolters Kluwer Health |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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