Local Inflammation in Arrhythmogenic Right Ventricular Cardiomyopathy (LI-ARVC)

The understanding of ARVC pathophysiology remains incomplete. Several clues indicate that disease progression is mediated through inflammation. The present study aim to document the feasibility of detecting the potential presence of intracardiac local inflammatory components in patients with ARVC.

Study Overview

• Status: Recruiting
• Conditions: Arrhythmogenic Right Ventricular Dysplasia
• Intervention / Treatment: Biological: Peripheral immunological assessment on venous blood; Biological: Immunological assessment carried out on intracardiac material

Detailed Description

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable condition characterized by right ventricular (RV) dilatation/dysfunction and malignant ventricular arrhythmias. The understanding of ARVC pathophysiology remains incomplete. Several clues indicate that disease progression is mediated through inflammation. First, presence of subepicardial late gadolinium enhancement sharing the same characteristics as the ones found in myocarditis is common on cardiac magnetic resonance imaging (CMR). Second, clinical pathology findings of inflammatory infiltrates of mononuclear cells are frequent and correlate to the extent and severity of ARVC. Finally, from a biological standpoint, the exploratory study conducted by Campian et al. has shown an exaggerated humoral inflammatory response in peripheral blood whilst anti-desmoglein-2 antibodies (targeting a component of the desmosome) emerge as a sensitive and specific biomarker for ARVC. As specific treatments for ARVC are currently lacking, a better understanding of the humoral pathophysiology of the disease could unlock new therapeutic targets. We recently demonstrated that collecting local cardiomyocytes was feasible through irrigated ablation catheters in patients with ARVC. These steerable catheters may easily map the whole right ventricle and locate endocardial or epicardial scars. Aspiration of local blood or cellular material through the inner lumen of the catheter once pressed on the parietal wall may be an interesting technique for retrieving local inflammation markers.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Philippe MAURY, MD; Phone Number: +33 5 61 32 34 70; Email: maury.p@chu-toulouse.fr
• Study Contact Backup: Name: Maxime BENEYTO; Email: beneyto.m@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France
    • Recruiting
    • Toulouse University Hospital Center
    • Principal Investigator: Philippe MAURY
    • Sub-Investigator: Maxime BENEYTO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For cases:

  • Arrhythmogenic right ventricular dysplasia diagnosed (according to 2010 Task Force Criteria)
  • Admitted for right ventricle electrophysiologic mapping
• For controls * Admitted for ablation procedures (accessory pathway, atrial flutter) on otherwise healthy hearts.

Exclusion Criteria:

• Diagnostic of systemic chronic inflammatory disease
• Presence of possible or proven cardiac involvement of an inflammatory disease, an acute or chronic infectious disease.
• Taking immunosuppressant or immunomodulating medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients; Carrier of a definite diagnosis of arrhythmogenic dysplasia of the right ventricle in line with the criteria of the Task Force 2010 (see Appendices), admitted for an electrical mapping of the right ventricle	Biological: Peripheral immunological assessment on venous blood; Peripheral immunological assessment carried out as part of the research, on venous blood at the puncture point necessary for the electrophysiological examination: 1 heparin tube and 1 EDTA tube; Biological: Immunological assessment carried out on intracardiac material; Immunological assessment carried out as part of the research, on intracardiac material taken during the electrophysiological examination: 1 EDTA tube
Experimental: Control case; Without heart disease, admitted for a Kent bundle ablation or endocavity procedure / Wolff-Parkinson-White syndrome or common flutter (in subjects in whom the same irrigated material will be used and for whom echocardiography will have excluded associated heart disease).	Biological: Peripheral immunological assessment on venous blood; Peripheral immunological assessment carried out as part of the research, on venous blood at the puncture point necessary for the electrophysiological examination: 1 heparin tube and 1 EDTA tube; Biological: Immunological assessment carried out on intracardiac material; Immunological assessment carried out as part of the research, on intracardiac material taken during the electrophysiological examination: 1 EDTA tube

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify the inflammatory components by C-reactive protein	Rate of C-reactive protein in the blood	24 months
Identify the inflammatory components by interleukine1	Rate of interleukin 1 beta in the blood	24 months
Identify the inflammatory components by onterleukine6	Rate of interleukin 6 in the blood	24 months
Identify the inflammatory components by interleukine10	Rate of interleukin 10 in the blood	24 months
Identify the inflammatory components by Tumor Necrosis Factor	Rate of Tumor Necrosis Factor alpha in the blood	24 months
Identify the inflammatory components by Transforming Growth Factor	Rate of Transforming Growth Factor beta in the blood	24 months

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: January 12, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): January 27, 2022

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; Tumor Necrosis Factor-alpha; Cytokines; Transforming Growth Factor beta; Interleukin-6; Interleukin-1; Interleukin-10; Cardiac Electrophysiologic Techniques
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Inflammation; Cardiomyopathies; Arrhythmogenic Right Ventricular Dysplasia
• Other Study ID Numbers: RC31/21/0026

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