1. Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy.
- Author
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Dal Ferro M, Stolfo D, Altinier A, Gigli M, Perrieri M, Ramani F, Barbati G, Pivetta A, Brun F, Monserrat L, Giacca M, Mestroni L, Merlo M, and Sinagra G
- Subjects
- Adult, Cardiomyopathy, Dilated diagnosis, Chi-Square Distribution, DNA Mutational Analysis methods, Female, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Italy, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Phenotype, Registries, Retrospective Studies, Risk Factors, Stroke Volume, Time Factors, Cardiomyopathy, Dilated genetics, Cardiomyopathy, Dilated physiopathology, Multigene Family, Mutation, Ventricular Function, Left, Ventricular Remodeling
- Abstract
Objective: To explore the genetic landscape of a well selected dilated cardiomyopathy (DCM) cohort, assessing the possible relation between different genotypes and left ventricular reverse remodelling (LVRR)., Methods: A cohort of 152 patients with DCM from the Heart Muscle Disease Registry of Trieste has been studied by next-generation sequencing (NGS). Patients were grouped into different 'gene-clusters' with functionally homogeneous genetic backgrounds. LVRR was defined by left ventricular ejection fraction normalisation or increase ≥10% associated with normalisation in indexed left ventricular end-diastolic diameter or relative decrease ≥10% at 24 months follow-up., Results: A pathogenic disease-related gene variant was identified in 57% of patients: 28 (18%) TTN ; 7 (5%) LMNA ; 16 (11%) structural cytoskeleton Z-disk genes; 9 (6%) desmosomal genes; 18 (12%) motor sarcomeric genes and 9 (6%) other genes. Baseline clinical features were similar throughout the different genotypes. A significant relationship was found between gene cluster subgroups and LVRR, with a lower rate of LVRR in structural cytoskeleton Z-disk gene mutation carriers (1/16 patients, 6%, p<0.05 vs the other subgroups). Of note, structural cytoskeleton Z-disk gene rare variants were independently and inversely associated with LVRR when adjusted for clinical predictors of LVRR (OR 0.065; 95% CI 0.008 to 0.535, p=0.011)., Conclusions: NGS confirmed a high genetic diagnostic yield in DCM. A specific 'gene-clusters' classification based on functional similarities in different genes might be helpful in the clinical management of genetically determined DCM. In this study, structural cytoskeleton Z-disk gene rare variants were independently associated with a lower rate of LVRR at follow-up., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2017
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