DNA Analysis From Isolated Cardiomyocytes in the Molecular Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (FA2CM-DVDA)

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

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.

Study Overview

• Status: Completed
• Conditions: Arrhythmogenic Right Ventricular Cardiomyopathy; Arrhythmogenic Right Ventricular Dysplasia
• Intervention / Treatment: Diagnostic test: Cardiomyocytes collection

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Philippe MAURY, MD; Phone Number: +33(0)561323054; Email: maury.p@chu-toulouse.fr

Study Locations

• France
  • Paris, France
    • Cardiology-rytmology service
  • Toulouse, France, 31000
    • University Hospital Toulouse - Cardiology Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Cardiomyocytes collection; Patients suffering from arrhythmogenic right ventricular cardiomyopathy/dysplasia cardiac and needing endocardial voltage mapping for disease diagnosis and/or prognosis assessment	Diagnostic test: Cardiomyocytes collection; collect intact cardiomyocytes from which high quality DNA extraction will be achieved

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of patients	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.	inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mutation percentage	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	Inclusion
DNA results	Concordance of results of DNA analysis between blood cells and cardiomyocytes	Inclusion
Epigenetic analysis	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.	Inclusion
Cardiomyocytes number Description:	Number of intact cardiomyocytes collected in each patient	Inclusion
Percentage of cardiomyocytes	Percentage of cardiomyocytes from which isolation of high quality DNA will be achieved	Inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Philippe MAURY, MD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2016
• Primary Completion (Actual): February 23, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: June 2, 2017
• First Submitted That Met QC Criteria: June 2, 2017
• First Posted (Actual): June 6, 2017

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiomyopathies; Arrhythmogenic Right Ventricular Dysplasia
• Other Study ID Numbers: RC31/15/7731

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No