Escobar-Lopez, LuisOchoa, Juan PabloMirelis, Jesús GEspinosa, María ÁngelesNavarro, MarinaGallego-Delgado, MaríaBarriales-Villa, RobertoRobles-Mezcua, AinhoaBasurte-Elorz, María TeresaGutiérrez García-Moreno, LauraCliment, VicenteJiménez-Jaimez, JuanMogollón-Jiménez, María VictoriaLopez, JavierPeña-Peña, María LuisaGarcía-Álvarez, AnaBrion, MaríaRipoll-Vera, TomasPalomino-Doza, JuliánTirón, ColomaIdiazabal, UxuaBrögger, Maria NoëlGarcía-Hernández, SoledadRestrepo-Córdoba, María AlejandraGonzalez-Lopez, EstherMéndez, IreneSabater, MaríaVillacorta, EduardoLarrañaga-Moreira, José MAbecia, AnaFernández, Ana IsabelGarcía-Pinilla, José MRodríguez-Palomares, José FGimeno-Blanes, Juan RamónBayes-Genis, AntoniLara-Pezzi, EnriqueDomínguez, FernandoGarcia-Pavia, Pablo2025-01-072025-01-072021https://hdl.handle.net/10668/26486The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. 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). 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: 1.09-2.07; 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  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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/dilated cardiomyopathygeneticsheart failureleft ventricular reverse remodelingmutationprognosissudden cardiac deathventricular arrhythmiaAdultAgedArrhythmias, CardiacCardiomyopathy, DilatedFemaleGenetic VariationGenotypeHeart FailureHeart VentriclesHumansLongitudinal StudiesMaleMiddle AgedRetrospective StudiesRiskStroke VolumeTreatment OutcomeVentricular DysfunctionVentricular Function, LeftVentricular Remodelingresearch article34674813open access10.1016/j.jacc.2021.08.0391558-3597http://ddfv.ufv.es/bitstream/10641/2645/1/3.-%20Association%20of%20genetic%20variants%20and%20outcomes%20in%20non-ischemic.pdf