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DNA Analysis From Isolated Cardiomyocytes in the Molecular Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Not Applicable
Completed
Conditions
Arrhythmogenic Right Ventricular Cardiomyopathy
Arrhythmogenic Right Ventricular Dysplasia
Interventions
Diagnostic Test: Cardiomyocytes collection
Registration Number
NCT03177018
Lead Sponsor
University Hospital, Toulouse
Brief Summary

The main objective of this study is to assess if it is possible, at the end of endocardial voltage mapping, to accurately collect intact cardiomyocytes and to isolate high quality DNA allowing molecular testing of selected genes involved in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Detailed Description

Arrhythmogenic right ventricular cardiomyopathy/dysplasia is associated with mutations in genes encoding proteins from desmosomes and is characterized by a large expression variability. The classical molecular diagnosis from blood cells fails to identify mutations in around 30% of patients. Probes used for endocardial voltage mapping allow to collect some cardiomyocytes which could be used for DNA analysis.

The aim of this project is to investigate if cardiomyocytes can efficiently be collected during endocardial voltage mapping in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Thirty patients suffering from arrhythmogenic right ventricular cardiomyopathy/dysplasia cardiac and needing endocardial voltage mapping for disease diagnosis and/or prognosis assessment will be included. The main outcome will be the percentage of patients in whom mapping will allow to collect intact cardiomyocytes from which high quality DNA extraction will be achieved. Other outcomes include the identification of new mutational mechanisms as somatic mosaicism in selected genes (PKP2, DSCG2 DSP) and the feasibility of epigenetic analysis of these genes.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
34
Inclusion Criteria
  • patients needing endocardial voltage mapping in the context of arrhythmogenic right ventricular cardiomyopathy/dysplasia diagnosed using current criteria
Exclusion Criteria
  • Patient under 18 years, pregnant women and patients under legal protection

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Patients with Cardiomyocytes collectionCardiomyocytes collectionPatients suffering from arrhythmogenic right ventricular cardiomyopathy/dysplasia cardiac and needing endocardial voltage mapping for disease diagnosis and/or prognosis assessment
Primary Outcome Measures
NameTimeMethod
percentage of patientsinclusion

Percentage of patients undergoing endocardial voltage mapping for arrhythmogenic right ventricular cardiomyopathy/dysplasia in whom at least one intact cardiomyocyte allowing extraction of high quality DNA will be collected.

Secondary Outcome Measures
NameTimeMethod
DNA resultsInclusion

Concordance of results of DNA analysis between blood cells and cardiomyocytes

Mutation percentageInclusion

Percentage of cases in which a mutation of at least one of three selected genes involved in arrhythmogenic right ventricular cardiomyopathy/dysplasia will be identified

Percentage of cardiomyocytesInclusion

Percentage of cardiomyocytes from which isolation of high quality DNA will be achieved

Cardiomyocytes number Description:Inclusion

Number of intact cardiomyocytes collected in each patient

Epigenetic analysisInclusion

Number of cases where epigenetic analysis of the three selected genes PKP2, DSP, DSG2 from cardiomyocyte DNA could be performed and comparison with DNA methylation observed from blood cells DNA.

Trial Locations

Locations (2)

Cardiology-rytmology service

🇫🇷

Paris, France

University Hospital Toulouse - Cardiology Department

🇫🇷

Toulouse, France

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