Association of Genetic Variants With Outcomes in Patients With Nonischemic Dilated Cardiomyopathy.
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Escobar-Lopez Luis, Ochoa Juan Pablo, Mirelis Jesús G, Espinosa María Ángeles, Navarro Marina, Gallego-Delgado María, Barriales-Villa Roberto, Robles-Mezcua Ainhoa, Basurte-Elorz María Teresa, Gutiérrez García-Moreno Laura, Climent Vicente, Jiménez-Jaimez Juan, Mogollón-Jiménez María Victoria, Lopez Javier, Peña-Peña María Luisa, García-Álvarez Ana, Brion María, Ripoll-Vera Tomas, Palomino-Doza Julián, Tirón Coloma, Idiazabal Uxua, Brögger Maria Noël, García-Hernández Soledad, Restrepo-Córdoba María Alejandra, Gonzalez-Lopez Esther, Méndez Irene, Sabater María, Villacorta Eduardo, Larrañaga-Moreira José M, Abecia Ana, Fernández Ana Isabel, García-Pinilla José M, Rodríguez-Palomares José F, Gimeno-Blanes Juan Ramón, Bayes-Genis Antoni, Lara-Pezzi Enrique, Domínguez Fernando, Garcia-Pavia Pablo
Аннотация
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: 1.09-2.07; 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.
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.