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

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Abstract

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: 1.09-2.07; 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.

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Escobar-Lopez, L., Ochoa, J. P., Mirelis, J. G., Espinosa, M. Á., Navarro, M., Gallego-Delgado, M., … Garcia-Pavia, P. (2021). Association of Genetic Variants With Outcomes in Patients With Nonischemic Dilated Cardiomyopathy. Journal of the American College of Cardiology, 78(17), 1682–1699. https://doi.org/10.1016/j.jacc.2021.08.039

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