Mora-Ayestarán, NereaOchoa, Juan PabloEspinosa-Castro, María ÁngelesNavarro-Peñalver, MarinaVillacorta, EduardoCrespo-Leiro, María GCliment-Payá, VicenteLacuey-Lecumberri, GemmaPeña-Peña, María LuisaBermúdez-Jiménez, Francisco JGarcía-Pinilla, José MMogollón-Jiménez, María VictoriaLimeres-Freire, JavierGarcía-Álvarez, AnaBayés-Genís, AntoniPalomino-Doza, JuliánTirón, ColomaRipoll-Vera, TomásLópez, JavierBrion, MaríaVilches-Soria, SilviaSabater-Molina, MaríaGarcía-Berrocal, BelénLarrañaga-Moreira, José MGarcía-Álvarez, María IBasurte-Elorz, María TeresaLlamas-Gómez, HelenaMéndez-Fernández, IreneGarrido-Bravo, Iris PaulaGonzález-López, EstherGallego-Delgado, MaríaBarriales-Villa, RobertoLara-Pezzi, EnriqueGarcía-Pavía, PabloDomínguez, Fernando2025-12-162025-12-162025-10-09Rev Esp Cardiol (Engl Ed). 2025 Oct 9:S1885-5857(25)00273-7.https://hdl.handle.net/20.500.12105/27043Left ventricular reverse remodeling (LVRR) is a key therapeutic goal in dilated cardiomyopathy (DCM). However, its genetic predictors and prognostic impact remain uncertain. We analyzed genotyped DCM patients with serial echocardiograms from the Spanish DCM study. The main objective was to assess the influence of genotype on LVRR, defined by improvement in ejection fraction within 12± 6 months. Secondary endpoints included major adverse cardiovascular events, end-stage heart failure (HF), and malignant ventricular arrhythmias. A total of 711 patients were included (67% male, mean age 50.8 years, baseline ejection fraction 31%, 44% genotype positive). LVRR occurred in 39% of genotype-positive vs 47% of genotype-negative patients (P=.036). Independent predictors of LVRR were TTN variants, lower baseline ejection fraction, and HF admission at diagnosis. In contrast, desmosomal, nuclear envelope and motor sarcomeric gene variants were associated with a lower likelihood of LVRR. During a median follow-up of 4.5 years, 26% of patients with initial LVRR showed subsequent deterioration, which was more frequent among genotype-positive individuals (32% vs 22%, P=.054). Compared with patients with sustained LVRR, those with deterioration had worse outcomes, including higher rates of major cardiovascular events (25% vs 7%), end-stage HF (18% vs 1%), and ventricular arrhythmia (12% vs 4%) (all P <.05). Genotype is a major determinant of both initial and long-term LVRR. Loss of ejection fraction improvement is common and strongly associated with adverse outcomes.This work was supported by grants from Instituto de Salud Carlos III “PI20/0320” (co-funded by the 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).engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/Dilated cardiomyopathyFracción de eyección del ventrículo izquierdoGeneticsGenéticaLeft ventricular ejection fractionMiocardiopatía dilatadaPrognosisPronósticoRemodeladoRemodelingAttribution-NonCommercial-NoDerivatives 4.0 International41067410REVISTA ESPANOLA DE CARDIOLOGIAopen access