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, Pablo2026-02-272026-02-272021-10-26J Am Coll Cardiol. 2021 Oct 26;78(17):1682-1699.https://hdl.handle.net/20.500.12105/27281The 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 < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene. 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.This work was supported by grants from the following institutions: the Instituto de Salud Carlos III (AC16/0014, PI18/0004, PI20/0320) and the European Union (GENPROVIC project from ERA-CVD framework). The Hospital Universitario Puerta de Hierro 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). All authors have reported that they have no relationships relevant to the contents of this paper to disclose.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/dilated cardiomyopathygeneticsheart failureleft ventricular reverse remodelingmutationprognosissudden cardiac deathventricular arrhythmiaAttribution-NonCommercial-NoDerivatives 4.0 International34674813JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGYopen access