Association of Genetic Variants With Outcomes in Patients With Nonischemic Dilated Cardiomyopathy

BACKGROUND The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. OBJECTIVES The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. METHODS Baseline and longitudinal clinical data from 1,005 genotyped DCM probands we...

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Detalles Bibliográficos
Autores: Escobar-Lopez, L, Ochoa, JP, Mirelis, JG, Espinosa, MA, Navarro, M, Gallego-Delgado, M, Barriales-Villa, R, Robles-Mezcua, A, Basurte-Elorz, MT, Garcia-Moreno, LG, Climent, V, Jimenez-Jaimez, J, Mogollon-Jimenez, MV, Lopez, J, Pena-Pena, ML, Garcia-Alvarez, A, Brion, M, Ripoll-Vera, T, Palomino-Doza, J, Tiron, C, Idiazabal, U, Brogger, MN, Garcia-Hernandez, S, Restrepo-Cordoba, MA, Gonzalez-Lopez, E, Mendez, I, Sabater, M, Villacorta, E, Larranaga-Moreira, JM, Abecia, A, Fernandez, AI, Garcia-Pinilla, JM, Rodriguez-Palomares, JF, Gimeno-Blanes, JR, Bayes-Genis, A, Lara-Pezzi, E, Dominguez, F, Garcia-Pavia, P
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p7589
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones7589
https://www.sciencedirect.com/science/article/abs/pii/S0735109721060861?via%3Dihub
Access Level:acceso abierto
Palabra clave:dilated cardiomyopathy
genetics
heart failure
left ventricular reverse remodeling
mutation
prognosis
sudden cardiac death
ventricular arrhythmia
Descripción
Sumario:BACKGROUND The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. OBJECTIVES The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. METHODS Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR) RESULTS After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.092.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction #35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene. CONCLUSIONS In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene. (J Am Coll Cardiol 2021;78:1682-1699) (c) 2021 by the American College of Cardiology Foundation.

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