Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives.

Autor:	Cabrera-Romero E; Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, the Netherlands., Ochoa JP; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, the Netherlands; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Health in Code, Madrid, Spain., Barriales-Villa R; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiac Diseases Unit, Department of Cardiology, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain; Instituto de Investigación Biomédica A Coruña (INIBIC), A Coruña, Spain., Bermúdez-Jiménez FJ; Department of Cardiology, Virgen de las Nieves University Hospital, Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain., Climent-Payá V; Heart Failure and Inherited Cardiac Diseases Unit, Cardiology Department, Hospital General Universitario Dr Balmis, Institute for Health and Biomedical Research of Alicante (ISABIAL), Alicante, Spain., Zorio E; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Department of Cardiology, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Clinical and Translational Research in Cardiology, Instituto de Investigación Sanitaria La Fe (IIS-La Fe), Valencia, Spain., Espinosa MA; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, the Netherlands; Department of Cardiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Facultad de Medicina, Universidad Complutense, Madrid, Spain., Gallego-Delgado M; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiovascular Disease Unit, Department of Cardiology, Complejo Asistencial Universitario de Salamanca, Institute for Biomedical Research of Salamanca (IBSAL), Gerencia Regional de Salud de Castilla y Leon (SACYL), Salamanca, Spain., Navarro-Peñalver M; Unidad CSUR/ERN de Cardiopatías Familiares, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain., Arana-Achaga X; Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Donostia University Hospital, Donostia, Spain; Biodonostia Health Research Institute, Donostia, Spain., Piqueras-Flores J; Inherited Cardiac Diseases Unit, Cardiology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain; Department of Medicine, Universidad de Castilla La Mancha, Ciudad Real, Spain; Health Research Institute of Castilla La Mancha (IDISCAM), Ciudad Real, Spain., Espejo-Bares V; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de investigación 12 de Octubre i+12, Madrid, Spain., Rodríguez-Palomares JF; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, the Netherlands; Cardiovascular Imaging Department and Inherited Cardiac Diseases Unit, Cardiology Department, Hospital Universitario Vall Hebrón, Barcelona, Spain; Vall Hebron Research Institute (VHIR), Universitat Autónoma de Barcelona (UAB), Barcelona, Spain., Lacuey-Lecumberri G; Hospital Universitario de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain., López J; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Hospital Clínico de Valladolid, Vallodolid, Spain; Instituto de Ciencias del Corazón (ICICOR), Valladolid, Spain., Tiron C; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitari Dr Josep Trueta, Girona, Spain; Medical Science Department, School of Medicine, University of Girona, Girona, Spain., Peña-Peña ML; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, the Netherlands; Cardiovascular Imaging and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Virgen del Rocío, Sevilla, Spain., García-Pinilla JM; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Heart Failure and Inherited Cardiac Diseases Unit, Hospital Universitario Virgen de la Victoria, IBIMA, Málaga, Spain; Departamento de Medicina y Dermatología, Universidad de Málaga, Málaga, Spain., Lorca R; Inherited Cardiac Diseases Unit, Área del Corazón, Hospital Universitario Central Asturias (HUCA), Oviedo, Spain; de Fisiología, Departamento de Biología Funcional, Universidad de Oviedo, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain; Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORs), Madrid, Spain., Ripoll-Vera T; Hospital Universitario Son Llatzer, IdISBa, Palma de Mallorca, Spain., Díez-López C; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiovascular Diseases Program, Hospital Universitari de Bellvitge, BioHeart Research Group, IDIBELL, Badalona, Spain., Mogollon MV; Department of Caardiology, Complejo Hospitalario Universitario de Cáceres, Caceres, Spain., García-Álvarez A; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, the Netherlands; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Cardiology Department, Hospital Clínic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain., Martínez-Dolz L; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Department of Cardiology, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Clinical and Translational Research in Cardiology, Instituto de Investigación Sanitaria La Fe (IIS-La Fe), Valencia, Spain., Brion M; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Xenética Cardiovascular, Instituto de investigación Sanitaria de Santiago, Inherited Cardiac Diseases Unit, Department of Cardiology Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain., Larrañaga-Moreira JM; Inherited Cardiac Diseases Unit, Department of Cardiology, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain; Instituto de Investigación Biomédica A Coruña (INIBIC), A Coruña, Spain., Jiménez-Jáimez J; Department of Cardiology, Virgen de las Nieves University Hospital, Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain., García-Álvarez MI; Heart Failure and Inherited Cardiac Diseases Unit, Cardiology Department, Hospital General Universitario Dr Balmis, Institute for Health and Biomedical Research of Alicante (ISABIAL), Alicante, Spain., Vilches S; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, the Netherlands; Department of Cardiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Facultad de Medicina, Universidad Complutense, Madrid, Spain., Villacorta E; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiovascular Disease Unit, Department of Cardiology, Complejo Asistencial Universitario de Salamanca, Institute for Biomedical Research of Salamanca (IBSAL), Gerencia Regional de Salud de Castilla y Leon (SACYL), Salamanca, Spain; Universidad de Salamanca, Salamanca, Spain., Sabater-Molina M; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Unidad CSUR/ERN de Cardiopatías Familiares, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain; Laboratorio de Cardiogenética, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain; Departamento de Ciencias Sociosanitarias, Universidad de Murcia, Murcia, Spain., Solla-Ruiz I; Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Donostia University Hospital, Donostia, Spain; Biodonostia Health Research Institute, Donostia, Spain., Royuela A; Biostatistics Unit, Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERESP, Madrid, Spain., Domínguez F; Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, the Netherlands; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Mirelis JG; Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Electronic address: pablogpavia@yahoo.es., Garcia-Pavia P; Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERN GUARD-Heart, Amsterdam, the Netherlands; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcón, Spain.
Jazyk:	angličtina
Zdroj:	Journal of the American College of Cardiology [J Am Coll Cardiol] 2024 Apr 30; Vol. 83 (17), pp. 1640-1651.
DOI:	10.1016/j.jacc.2024.02.036
Abstrakt:	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%) identified 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. Competing Interests: Funding Support and Author Disclosures This study was funded by the Spanish Society of Cardiology (Grant in Inherited Cardiac Diseases 2022) and the Instituto de Salud Carlos III through the projects “PI18/0004, 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. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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