Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives

BACKGROUND Disease penetrance in genotype -positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to id...

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Autores: Cabrera Romero, Eva, Ochoa, Juan Pablo, Barriales Villa, Roberto, Bermúdez Jiménez, Francisco José, Climent Payá, Vicente, Zorio, Esther, Espinosa, María Angeles, Gallego Delgado, María, Navarro Peñalver, Marina, Arana Achaga, Xabier, Piqueras Flores, Jesús, Espejo Bares, Victoria, Rodríguez Palomares, José F., Lacuey Lecumberri, Gemma, López, Javier, Tiron, Coloma, Peña Peña, María Luisa, García Pinilla, José Manuel, Lorca, Rebeca, Ripoll Vera, Tomás, Díez López, Carles, Mogollón Jiménez, María Victoria, García Álvarez, Ana, Martínez Dolz, Luis, Brión, María, Larrañaga Moreira, Jose María, Jiménez Jáimez, Juan, García Álvarez, María Isabel, Vilches Saez, Silvia, Villacorta, Eduardo, Sabater Molina, María, Solla Ruiz, Itziar, Royuela, Ana, Domínguez, Fernando, Mirelis, Jesús G., García Pavía, Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/214161
Acceso en línea:https://hdl.handle.net/2445/214161
Access Level:acceso abierto
Palabra clave:Miocardiopaties
Genètica humana
Myocardiopathies
Human genetics
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spelling Penetrance of Dilated Cardiomyopathy in Genotype-Positive RelativesCabrera Romero, EvaOchoa, Juan PabloBarriales Villa, RobertoBermúdez Jiménez, Francisco JoséCliment Payá, VicenteZorio, EstherEspinosa, María AngelesGallego Delgado, MaríaNavarro Peñalver, MarinaArana Achaga, XabierPiqueras Flores, JesúsEspejo Bares, VictoriaRodríguez Palomares, José F.Lacuey Lecumberri, GemmaLópez, JavierTiron, ColomaPeña Peña, María LuisaGarcía Pinilla, José ManuelLorca, RebecaRipoll Vera, TomásDíez López, CarlesMogollón Jiménez, María VictoriaGarcía Álvarez, AnaMartínez Dolz, LuisBrión, MaríaLarrañaga Moreira, Jose MaríaJiménez Jáimez, JuanGarcía Álvarez, María IsabelVilches Saez, SilviaVillacorta, EduardoSabater Molina, MaríaSolla Ruiz, ItziarRoyuela, AnaDomínguez, FernandoMirelis, Jesús G.García Pavía, PabloMiocardiopatiesGenètica humanaMyocardiopathiesHuman geneticsBACKGROUND Disease penetrance in genotype -positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS The authors evaluated 779 G+ patients (age 35.8 +/- 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN ) without DCM followed at 25 Spanish centers. RESULTS After a median follow-up of 37.1 months (Q1 -Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person -years; 95% CI: 2.3-3.5 per 100 person -years). DCM penetrance and age at DCM onset was different according to underlying gene group (log -rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1 -year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end -diastolic diameter (HR per 1 -mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identi fied late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end -diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM. (J Am Coll Cardiol 2024;83:1640 -1651) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Elsevier BV2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/214161Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.jacc.2024.02.036Journal of the American College of Cardiology, 2024, vol. 83, num. 17, p. 1640-1651https://doi.org/10.1016/j.jacc.2024.02.036cc by-nc-nd (c) Cabrera Romero, Eva et al, 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2141612026-05-27T06:46:51Z
dc.title.none.fl_str_mv Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives
title Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives
spellingShingle Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives
Cabrera Romero, Eva
Miocardiopaties
Genètica humana
Myocardiopathies
Human genetics
title_short Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives
title_full Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives
title_fullStr Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives
title_full_unstemmed Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives
title_sort Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives
dc.creator.none.fl_str_mv Cabrera Romero, Eva
Ochoa, Juan Pablo
Barriales Villa, Roberto
Bermúdez Jiménez, Francisco José
Climent Payá, Vicente
Zorio, Esther
Espinosa, María Angeles
Gallego Delgado, María
Navarro Peñalver, Marina
Arana Achaga, Xabier
Piqueras Flores, Jesús
Espejo Bares, Victoria
Rodríguez Palomares, José F.
Lacuey Lecumberri, Gemma
López, Javier
Tiron, Coloma
Peña Peña, María Luisa
García Pinilla, José Manuel
Lorca, Rebeca
Ripoll Vera, Tomás
Díez López, Carles
Mogollón Jiménez, María Victoria
García Álvarez, Ana
Martínez Dolz, Luis
Brión, María
Larrañaga Moreira, Jose María
Jiménez Jáimez, Juan
García Álvarez, María Isabel
Vilches Saez, Silvia
Villacorta, Eduardo
Sabater Molina, María
Solla Ruiz, Itziar
Royuela, Ana
Domínguez, Fernando
Mirelis, Jesús G.
García Pavía, Pablo
author Cabrera Romero, Eva
author_facet Cabrera Romero, Eva
Ochoa, Juan Pablo
Barriales Villa, Roberto
Bermúdez Jiménez, Francisco José
Climent Payá, Vicente
Zorio, Esther
Espinosa, María Angeles
Gallego Delgado, María
Navarro Peñalver, Marina
Arana Achaga, Xabier
Piqueras Flores, Jesús
Espejo Bares, Victoria
Rodríguez Palomares, José F.
Lacuey Lecumberri, Gemma
López, Javier
Tiron, Coloma
Peña Peña, María Luisa
García Pinilla, José Manuel
Lorca, Rebeca
Ripoll Vera, Tomás
Díez López, Carles
Mogollón Jiménez, María Victoria
García Álvarez, Ana
Martínez Dolz, Luis
Brión, María
Larrañaga Moreira, Jose María
Jiménez Jáimez, Juan
García Álvarez, María Isabel
Vilches Saez, Silvia
Villacorta, Eduardo
Sabater Molina, María
Solla Ruiz, Itziar
Royuela, Ana
Domínguez, Fernando
Mirelis, Jesús G.
García Pavía, Pablo
author_role author
author2 Ochoa, Juan Pablo
Barriales Villa, Roberto
Bermúdez Jiménez, Francisco José
Climent Payá, Vicente
Zorio, Esther
Espinosa, María Angeles
Gallego Delgado, María
Navarro Peñalver, Marina
Arana Achaga, Xabier
Piqueras Flores, Jesús
Espejo Bares, Victoria
Rodríguez Palomares, José F.
Lacuey Lecumberri, Gemma
López, Javier
Tiron, Coloma
Peña Peña, María Luisa
García Pinilla, José Manuel
Lorca, Rebeca
Ripoll Vera, Tomás
Díez López, Carles
Mogollón Jiménez, María Victoria
García Álvarez, Ana
Martínez Dolz, Luis
Brión, María
Larrañaga Moreira, Jose María
Jiménez Jáimez, Juan
García Álvarez, María Isabel
Vilches Saez, Silvia
Villacorta, Eduardo
Sabater Molina, María
Solla Ruiz, Itziar
Royuela, Ana
Domínguez, Fernando
Mirelis, Jesús G.
García Pavía, Pablo
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
dc.subject.none.fl_str_mv Miocardiopaties
Genètica humana
Myocardiopathies
Human genetics
topic Miocardiopaties
Genètica humana
Myocardiopathies
Human genetics
description BACKGROUND Disease penetrance in genotype -positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS The authors evaluated 779 G+ patients (age 35.8 +/- 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN ) without DCM followed at 25 Spanish centers. RESULTS After a median follow-up of 37.1 months (Q1 -Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person -years; 95% CI: 2.3-3.5 per 100 person -years). DCM penetrance and age at DCM onset was different according to underlying gene group (log -rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1 -year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end -diastolic diameter (HR per 1 -mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identi fied late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end -diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM. (J Am Coll Cardiol 2024;83:1640 -1651) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/214161
url https://hdl.handle.net/2445/214161
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.jacc.2024.02.036
Journal of the American College of Cardiology, 2024, vol. 83, num. 17, p. 1640-1651
https://doi.org/10.1016/j.jacc.2024.02.036
dc.rights.none.fl_str_mv cc by-nc-nd (c) Cabrera Romero, Eva et al, 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Cabrera Romero, Eva et al, 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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