Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure

Background and Certain genetic forms of dilated cardiomyopathy (DCM) entail a higher arrhythmic risk. It is unknown whether DCM pa-aims tients with high-risk arrhythmic genotypes also develop more advanced heart failure (AHF) complications. AHF events were studied according to DCM genotype. Methods...

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Autores: Mora-Ayestarán, Nerea, Ochoa, Juan Pablo, Gómez-González, Cristina, Navarro-Peñalver, Marina, Gallego-Delgado, María, Larrañaga-Moreira, José M., Robles-Mezcua, Ainhoa, Basurte-Elorz, María Teresa, Rodriguez-Palomares, Jose Fernando, Climent-Paya, Vicente, Jiménez-Jaímez, Juan, Mogollón-Jiménez, Maria Victoria, García-Granja, Pablo Elpidio, García-Álvarez, Ana, Peña-Peña, María Luisa, Barredo, María Alvarez, Ripoll-Vera, Tomas, Palomino-Doza, Julián, Bayes-Genis, Antoni, Tirón, Coloma, Fernández, Ana Isabel, Sabater-Molina, María, Toranzo, Inés, Crespo-Leiro, María G., Doncel-Abad, Victoria, Lacuey-Lecumberri, Gemma, Limeres-Freire, Javier, García-Álvarez, Maria I., Cabrera-Borrego, Eva, El Maalem, Zineb Kounka Ait, Vilches, Silvia, González-López, Esther, Villacorta, Eduardo, García-Pinilla, José M., Barriales-Villa, Roberto, Gimeno-Blanes, Juan Ramón, Garcia-Pavia, Pablo, Domínguez, Fernando
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:dnet:recercat____::6c12c3908bce92687fc645425a1250a1
Acceso en línea:http://hdl.handle.net/10256/28844
https://hdl.handle.net/10256/28844
Access Level:acceso abierto
Palabra clave:Genes
Heart failure
Prognosis
Cor -- Malalties
Heart -- Diseases
Gens
Insuficiència cardíaca
Prognosi
Sudden death
Mort sobtada
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dc.title.none.fl_str_mv Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure
title Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure
spellingShingle Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure
Mora-Ayestarán, Nerea
Genes
Heart failure
Prognosis
Cor -- Malalties
Heart -- Diseases
Gens
Insuficiència cardíaca
Prognosi
Sudden death
Mort sobtada
title_short Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure
title_full Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure
title_fullStr Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure
title_full_unstemmed Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure
title_sort Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure
dc.creator.none.fl_str_mv Mora-Ayestarán, Nerea
Ochoa, Juan Pablo
Gómez-González, Cristina
Navarro-Peñalver, Marina
Gallego-Delgado, María
Larrañaga-Moreira, José M.
Robles-Mezcua, Ainhoa
Basurte-Elorz, María Teresa
Rodriguez-Palomares, Jose Fernando
Climent-Paya, Vicente
Jiménez-Jaímez, Juan
Mogollón-Jiménez, Maria Victoria
García-Granja, Pablo Elpidio
García-Álvarez, Ana
Peña-Peña, María Luisa
Barredo, María Alvarez
Ripoll-Vera, Tomas
Palomino-Doza, Julián
Bayes-Genis, Antoni
Tirón, Coloma
Fernández, Ana Isabel
Sabater-Molina, María
Toranzo, Inés
Crespo-Leiro, María G.
Doncel-Abad, Victoria
Lacuey-Lecumberri, Gemma
Limeres-Freire, Javier
García-Álvarez, Maria I.
Cabrera-Borrego, Eva
El Maalem, Zineb Kounka Ait
Vilches, Silvia
González-López, Esther
Villacorta, Eduardo
García-Pinilla, José M.
Barriales-Villa, Roberto
Gimeno-Blanes, Juan Ramón
Garcia-Pavia, Pablo
Domínguez, Fernando
author Mora-Ayestarán, Nerea
author_facet Mora-Ayestarán, Nerea
Ochoa, Juan Pablo
Gómez-González, Cristina
Navarro-Peñalver, Marina
Gallego-Delgado, María
Larrañaga-Moreira, José M.
Robles-Mezcua, Ainhoa
Basurte-Elorz, María Teresa
Rodriguez-Palomares, Jose Fernando
Climent-Paya, Vicente
Jiménez-Jaímez, Juan
Mogollón-Jiménez, Maria Victoria
García-Granja, Pablo Elpidio
García-Álvarez, Ana
Peña-Peña, María Luisa
Barredo, María Alvarez
Ripoll-Vera, Tomas
Palomino-Doza, Julián
Bayes-Genis, Antoni
Tirón, Coloma
Fernández, Ana Isabel
Sabater-Molina, María
Toranzo, Inés
Crespo-Leiro, María G.
Doncel-Abad, Victoria
Lacuey-Lecumberri, Gemma
Limeres-Freire, Javier
García-Álvarez, Maria I.
Cabrera-Borrego, Eva
El Maalem, Zineb Kounka Ait
Vilches, Silvia
González-López, Esther
Villacorta, Eduardo
García-Pinilla, José M.
Barriales-Villa, Roberto
Gimeno-Blanes, Juan Ramón
Garcia-Pavia, Pablo
Domínguez, Fernando
author_role author
author2 Ochoa, Juan Pablo
Gómez-González, Cristina
Navarro-Peñalver, Marina
Gallego-Delgado, María
Larrañaga-Moreira, José M.
Robles-Mezcua, Ainhoa
Basurte-Elorz, María Teresa
Rodriguez-Palomares, Jose Fernando
Climent-Paya, Vicente
Jiménez-Jaímez, Juan
Mogollón-Jiménez, Maria Victoria
García-Granja, Pablo Elpidio
García-Álvarez, Ana
Peña-Peña, María Luisa
Barredo, María Alvarez
Ripoll-Vera, Tomas
Palomino-Doza, Julián
Bayes-Genis, Antoni
Tirón, Coloma
Fernández, Ana Isabel
Sabater-Molina, María
Toranzo, Inés
Crespo-Leiro, María G.
Doncel-Abad, Victoria
Lacuey-Lecumberri, Gemma
Limeres-Freire, Javier
García-Álvarez, Maria I.
Cabrera-Borrego, Eva
El Maalem, Zineb Kounka Ait
Vilches, Silvia
González-López, Esther
Villacorta, Eduardo
García-Pinilla, José M.
Barriales-Villa, Roberto
Gimeno-Blanes, Juan Ramón
Garcia-Pavia, Pablo
Domínguez, Fernando
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
dc.subject.none.fl_str_mv Genes
Heart failure
Prognosis
Cor -- Malalties
Heart -- Diseases
Gens
Insuficiència cardíaca
Prognosi
Sudden death
Mort sobtada
topic Genes
Heart failure
Prognosis
Cor -- Malalties
Heart -- Diseases
Gens
Insuficiència cardíaca
Prognosi
Sudden death
Mort sobtada
description Background and Certain genetic forms of dilated cardiomyopathy (DCM) entail a higher arrhythmic risk. It is unknown whether DCM pa-aims tients with high-risk arrhythmic genotypes also develop more advanced heart failure (AHF) complications. AHF events were studied according to DCM genotype. Methods Clinical data from 1203 genotyped DCM patients were collected from 19 Spanish centres. Patients were classified into high-risk arrhythmic genotypes (LMNA, FLNC, desmosomal genes, PLN, TMEM43, RBM20), TTN, other genes, and genotype negative (Gen−). The primary endpoint was a composite of AHF events (ventricular assist device implantation, heart transplant, and AHF-related mortality). The secondary endpoint was a combination of malignant ventricular arrhythmias (MVA). Results A DCM-causing variant was identified in a high-risk arrhythmic gene in 185 patients (15.4%), 193 (16.0%) had variants in TTN, 134 (11.1%) in other genes, and 691 (57.4%) were Gen−. After a median follow-up of 5.7 years (interquartile range 2.9–9.1 years), AHF events occurred in 45 (24.3%) patients in the high-risk arrhythmic group, while in 25 (18.7%), 25 (13.0%), and 70 (10.1%) patients with other genotypes, TTN, and Gen−, respectively (hazard ratio 1.85, 95% confidence interval 1.31–2.61 for high-risk arrhythmic genes compared with other groups). MVA occurred in 55 patients (29.7%) (hazard ratio 2.52, 95% confidence interval 1.81–3.51 for high-risk genotypes vs other groups). High-risk arrhythmic genotype was the main independent predictor of AHF in multivariate analysis. High-risk arrhythmic genotype and late gadolinium enhancement were independent predictors of MVA. Conclusions Patients with high-risk arrhythmic genotypes also experience more AHF events, supporting a differential therapeutic approach in this group of patients beyond sudden death prevention.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/28844
https://hdl.handle.net/10256/28844
url http://hdl.handle.net/10256/28844
https://hdl.handle.net/10256/28844
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/eurheartj/ehaf605
info:eu-repo/semantics/altIdentifier/issn/0195-668X
dc.rights.none.fl_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford Academic
publisher.none.fl_str_mv Oxford Academic
dc.source.none.fl_str_mv © European Heart Journal, any 2025, vol. 46, núm 48, p. 5222-5233
Articles publicats (D-CM)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failureMora-Ayestarán, NereaOchoa, Juan PabloGómez-González, CristinaNavarro-Peñalver, MarinaGallego-Delgado, MaríaLarrañaga-Moreira, José M.Robles-Mezcua, AinhoaBasurte-Elorz, María TeresaRodriguez-Palomares, Jose FernandoCliment-Paya, VicenteJiménez-Jaímez, JuanMogollón-Jiménez, Maria VictoriaGarcía-Granja, Pablo ElpidioGarcía-Álvarez, AnaPeña-Peña, María LuisaBarredo, María AlvarezRipoll-Vera, TomasPalomino-Doza, JuliánBayes-Genis, AntoniTirón, ColomaFernández, Ana IsabelSabater-Molina, MaríaToranzo, InésCrespo-Leiro, María G.Doncel-Abad, VictoriaLacuey-Lecumberri, GemmaLimeres-Freire, JavierGarcía-Álvarez, Maria I.Cabrera-Borrego, EvaEl Maalem, Zineb Kounka AitVilches, SilviaGonzález-López, EstherVillacorta, EduardoGarcía-Pinilla, José M.Barriales-Villa, RobertoGimeno-Blanes, Juan RamónGarcia-Pavia, PabloDomínguez, FernandoGenesHeart failurePrognosisCor -- MalaltiesHeart -- DiseasesGensInsuficiència cardíacaPrognosiSudden deathMort sobtadaBackground and Certain genetic forms of dilated cardiomyopathy (DCM) entail a higher arrhythmic risk. It is unknown whether DCM pa-aims tients with high-risk arrhythmic genotypes also develop more advanced heart failure (AHF) complications. AHF events were studied according to DCM genotype. Methods Clinical data from 1203 genotyped DCM patients were collected from 19 Spanish centres. Patients were classified into high-risk arrhythmic genotypes (LMNA, FLNC, desmosomal genes, PLN, TMEM43, RBM20), TTN, other genes, and genotype negative (Gen−). The primary endpoint was a composite of AHF events (ventricular assist device implantation, heart transplant, and AHF-related mortality). The secondary endpoint was a combination of malignant ventricular arrhythmias (MVA). Results A DCM-causing variant was identified in a high-risk arrhythmic gene in 185 patients (15.4%), 193 (16.0%) had variants in TTN, 134 (11.1%) in other genes, and 691 (57.4%) were Gen−. After a median follow-up of 5.7 years (interquartile range 2.9–9.1 years), AHF events occurred in 45 (24.3%) patients in the high-risk arrhythmic group, while in 25 (18.7%), 25 (13.0%), and 70 (10.1%) patients with other genotypes, TTN, and Gen−, respectively (hazard ratio 1.85, 95% confidence interval 1.31–2.61 for high-risk arrhythmic genes compared with other groups). MVA occurred in 55 patients (29.7%) (hazard ratio 2.52, 95% confidence interval 1.81–3.51 for high-risk genotypes vs other groups). High-risk arrhythmic genotype was the main independent predictor of AHF in multivariate analysis. High-risk arrhythmic genotype and late gadolinium enhancement were independent predictors of MVA. Conclusions Patients with high-risk arrhythmic genotypes also experience more AHF events, supporting a differential therapeutic approach in this group of patients beyond sudden death prevention.This work was supported by grants from Instituto de Salud Carlos III ‘PI20/0320’ (co-funded by European Regional Development Fund/European Social Fund ‘A way to make Europe’/‘Investing in your future’). The CNIC is supported by the ISCIII, MCIN, the Pro-CNIC Foundation, and the Severo Ochoa Centers of Excellence program (CEX2020-001041-S). The Hospital Universitario Puerta de Hierro, Hospital Clínic, Hospital Vall Hebron, Hospital Virgen del Rocío, Hospital Universitario Gregorio Marañon, and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart. P.G.-P. and F.D. were funded by the Pathfinder Cardiogenomics Programme of the European Innovation Council of the European Union (DCM-NEXT project; project 101115416).3Oxford Academic2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/28844https://hdl.handle.net/10256/28844© European Heart Journal, any 2025, vol. 46, núm 48, p. 5222-5233Articles publicats (D-CM)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1093/eurheartj/ehaf605info:eu-repo/semantics/altIdentifier/issn/0195-668XAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:dnet:recercat____::6c12c3908bce92687fc645425a1250a12026-05-29T05:05:01Z
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