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Heart. 2017 Nov;103(21):1704-1710. doi: 10.1136/heartjnl-2016-311017. Epub 2017 Apr 17.

Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy.

Author information

1
Cardiovascular Department, Azienda Sanitaria-Universitaria Integrata of Trieste "ASUITS", Trieste, Italy.
2
Department of Cardiology, Health in Code, Coruña, Spain.
3
Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
4
Cardiovascular Institute, University of Colorado Denver, Denver, USA.

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.

KEYWORDS:

Clinical Genetics; Echocardiography; Idiopathic Dilated Cardiomyopathy.

PMID:
28416588
DOI:
10.1136/heartjnl-2016-311017
[Indexed for MEDLINE]

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