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Eur Heart J Cardiovasc Imaging. 2019 Nov 8. pii: jez277. doi: 10.1093/ehjci/jez277. [Epub ahead of print]

Myocardial fibrosis in arrhythmogenic cardiomyopathy: a genotype-phenotype correlation study.

Author information

1
Cardiology Department, Hospital Universitario Virgen de las Nieves, Avda. De las Fuerzas Armadas 2, Granada, Spain.
2
Instituto de Investigación Biosanitaria ibs.GRANADA, Av. De las Fuerzas Armadas 2, Granada, Spain.
3
Department of Histology and Tissue Engineering Group, Faculty of Medicine, University of Granada, Avda. De la Investigación, 11, 18016, Granada, Spain.
4
Radiology Department, Hospital Universitario Virgen de las Nieves, Avda. De las Fuerzas Armadas 2, Granada, Spain.
5
Servicio de Patología Forense, Instituto de Medicina Legal, Avda. De la Innovación, 1, Granada, Spain.

Abstract

AIMS:

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a life-threatening entity with a highly heterogeneous genetic background. Cardiac magnetic resonance (CMR) imaging can identify fibrofatty scar by late gadolinium enhancement (LGE). Our aim is to investigate genotype-phenotype correlation in ARVC/D mutation carriers, focusing on CMR-LGE and myocardial fibrosis patterns.

METHODS AND RESULTS:

A cohort of 44 genotyped patients, 33 with definite and 11 with borderline ARVC/D diagnosis, was characterized using CMR and divided into groups according to their genetic condition (desmosomal, non-desmosomal mutation, or negative). We collected information on cardiac volumes and function, as well as LGE pattern and extension. In addition, available ventricular myocardium samples from patients with pathogenic gene mutations were histopathologically analysed. Half of the patients were women, with a mean age of 41.6 ± 17.5 years. Next-generation sequencing identified a potential pathogenic mutation in 71.4% of the probands. The phenotype varied according to genetic status, with non-desmosomal male patients showing lower left ventricular (LV) systolic function. LV fibrosis was similar between groups, but distribution in non-desmosomal patients was frequently located at the posterolateral LV wall; a characteristic LV subepicardial circumferential LGE pattern was significantly associated with ARVC/D caused by desmin mutation. Histological analysis showed increased fibrillar connective tissue and intercellular space in all the samples.

CONCLUSION:

Desmosomal and non-desmosomal mutation carriers showed different morphofunctional features but similar LV LGE presence. DES mutation carriers can be identified by a specific and extensive LV subepicardial circumferential LGE pattern. Further studies should investigate the specificity of LGE in ARVC/D.

KEYWORDS:

arrhythmogenic cardiomyopathy; cardiac magnetic resonance; desmin; histology; late gadolinium enhancement; myocardial fibrosis

PMID:
31702781
DOI:
10.1093/ehjci/jez277

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