Issue and Metabolic Characterization of Arrhythmogenic Cardiomyopathies by Hybrid PET-MRI Imaging, Impact of the Observed Profiles on the Phenotype and on the Evolution of Cardiomyopathy

Study Overview
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Brief Summary
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Status of the research project: The main complications of arrhythmogenic cardiomyopathies (AC) are sudden death, more rarely heart failure. Recently, data are emerging in favor of an associated role of myocardial inflammation and myocarditis in this pathology, but the impact of inflammation on the presentation and prognosis of the cardiomyopathy, as well as its mechanisms, are not clearly elucidated. To date, endomyocardial biopsy is the gold standard for documenting myocardial inflammation. Aim of the research: To evaluate the interest of a new hybrid PET-MR imaging tool for tissue and metabolic characterization of AC associating MRI and 18F-FDG PET, already used in inflammatory pathologies (cardiac sarcoidosis). Project description: Multicentric observational study of 80 patients with genetic AC undergoing PET-MR. Description of the observed profiles and their impact on the phenotype of the cardiomyopathy and its evolution, study of associated immunological mechanisms, correlation with available anatomopathological data. Expected results and perspectives: first non-invasive description of tissue and metabolic phenotype of AC by PET-MR imaging and its prognostic role, basis for pathophysiological and therapeutic research in case of confirmation of the performances of this imaging for the detection of myocardial inflammation.

Detailed Description
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Status of the research project: The main complications of arrhythmogenic cardiomyopathies (AC) are sudden death, more rarely heart failure. Recently, data are emerging in favor of an associated role of myocardial inflammation and myocarditis in this pathology, but the impact of inflammation on the presentation and prognosis of the cardiomyopathy, as well as its mechanisms, are not clearly elucidated. To date, endomyocardial biopsy is the gold standard for documenting myocardial inflammation. Aim of the research: To evaluate the interest of a new hybrid PET-MR imaging tool for tissue and metabolic characterization of AC associating MRI and 18F-FDG PET, already used in inflammatory pathologies (cardiac sarcoidosis). Project description: Multicentric observational study of 80 patients with genetic AC undergoing PET-MR. Description of the observed profiles and their impact on the phenotype of the cardiomyopathy and its evolution, study of associated immunological mechanisms, correlation with available anatomopathological data. Expected results and perspectives: first non-invasive description of tissue and metabolic phenotype of AC by PET-MR imaging and its prognostic role, basis for pathophysiological and therapeutic research in case of confirmation of the performances of this imaging for the detection of myocardial inflammation.

Official Title
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Tissue and Metabolic Characterization of Arrhythmogenic Cardiomyopathies by Hybrid PET-MRI Imaging, Impact of the Observed Profiles on the Phenotype and on the Evolution of Cardiomyopathy

Conditions
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Arrhythmogenic Cardiomyopathies

Intervention / Treatment
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* Other: Biocollection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female over 16 years old Exclusion Criteria: Patients and their relatives with left ventricular or biventricular AC and carrier of a pathogenic or likely pathogenic variant in one of the following genes : PKP2, DSG2, DSC2, JUP, DSP, DES, FLNC, PLN, LMNA, TMEM43, CDH2, BAG3, RYR2, RBM20 Consent form Exclusion Criteria : Sarcoidosis or known or diagnosed autoimmune disease History of myocardial infarction Patient under guardianship, curatorship or safeguard of justice

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients group<br>Patients and their relatives affected with left ventricular or biventricular AC and carrier of a pathogenic or likely pathogenic variant in one of the following genes : PKP2, DSG2, DSC2, JUP, DSP, DES, FLNC, PLN, LMNA, TMEM43, CDH2, BAG3, RYR2, RBM20 | Other: Biocollection<br>* serum<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET-RMI patients profile | Rate of patients observed in the different expected PET-MRI patterns in the left ventricle (no late enhancement and no PET fixation, late enhancement and no PET fixation, concordant late enhancement and PET fixation, discordant late enhancement and PET fixation). | one hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET-RMI patterns in the right ventricle | Rate of patients with different expected PET-MRI patterns in the right ventricle (no late enhancement and no PET fixation, late enhancement and no PET fixation, concordant late enhancement and PET fixation, discordant late enhancement and PET fixation) | one hour | 
| Prognosis according to PET-RMI patterns | Comparison of event rates (death, heart transplantation, resuscitated sudden death, hemodynamically unstable VT, syncopal VT, hospitalization for heart failure, myocarditis) observed during follow-up according to the different expected LV and RV PET-MRI profiles observed at inclusion | 15-32 months | 
| Cardiac auto-antibodies according to PET-RMI patterns | Comparison of the rates of patients with circulating cardiac autoantibodies detected by indirect immunofluorescence technique according to the different expected LV and RV PET-MRI profiles at inclusion | one hour | 
| Spatial concordance | Rate of spatial concordance of segments with late enhancement and PET fixation on bulls-eye representations according to AHA segmentation | one hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arrhythmogenic cardiomyopathies, PET-MR imaging, Myocardial inflammation, Prognosis, Cardiac auto-antibodies