Study of the Relation Between Lipid Myocardial Overload Evaluated by Cardiac Magnetic Resonance Imaging (MRI), Alteration of Longitudinal Myocardial Deformations by Echocardiography, and Clinical Achievements (Functional, Biological and Electrical) in Fabry Disease, and Its Outcomes.

Study Overview
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Brief Summary
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Anderson-Fabry disease is a genetic lysosomal storage disease, linked to chromosome X (gene GLA), responsible of enzyme synthesis deficit in α-galactosidase A with intracellular sphingolipids accumulation and multiorganic achievement. If renal complication is principally responsible of the pejorative evolution of the disease, it may also exist a cardiac achievement, symptomatic or not (heart failure symptoms including dyspnea, conduction abnormalities, supra-ventricular and ventricular arrhythmias), with or without left ventricular hypertrophy (LVH). Administration of agalsidase-α or ß, a genetic engineering synthetic equivalent of the deficient enzyme, should significantly slow disease evolution indeed reduce LVH. Some patients with Fabry disease without LVH should present, compared to healthy subjects, indirect early markers of intramyocyte lipid overload: in echocardiography, longitudinal myocardial deformation (strain) should be altered while ejection fraction is preserved, and in cardiac MRI, T1 mapping should be reduced1. This was also previously demonstrated in Fabry patients with LVH2. However, are these abnormalities of longitudinal deformation in echocardiography and of T1 mapping in MRI correlated to the presence of pejorative cardiac markers (such as clinical and functional tolerances, Brain Natriuretic Peptide (BNP) level and electrical complications)?

Conditions
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Fabry Disease

Intervention / Treatment
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* Diagnostic Test: Echocardiography at T0
* Diagnostic Test: Exercise test
* Biological: Biological assays
* Device: MRI with contrast agent injection
* Device: MRI without contrast agent injection
* Diagnostic Test: Echocardiography at M24


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients group : Adults (age ≥18 years), male and female. Patients diagnosed genetically having Fabry disease, with or without clinical cardiac symptoms and with different evolution stades of the disease. For female in age of procreation, efficient contraception will be required and a negative pregnancy test. Oral agreement of the patient after having read information note. Patient affiliated to social national Security registry. Healthy volunteers group: Adults (age ≥18 years), male and female. Unscathed of cardiovascular pathologies and cardiovascular risk factors. For female in age of procreation, efficient contraception will be required and a negative pregnancy test. Oral agreement of the patient after having read information note. Patient affiliated to social national Security registry. Exclusion Criteria: For the 2 groups : Extracardiac pathology limiting life expectancy <1 year (cancer). Pregnant or breastfeeding female. Claustrophobia. Mechanical prosthetic valve. Severe obesity > 140 kg Patients with intracardiac device (implantable cardiac defibrillator, pace maker, resynchronisation), surgical clips not MRI compatible, neurosensorial stimulators, cochlear implants, ferromagnetic foreign bodies (ocular, cerebral), neurosurgical derivation valves) Impossibility to provide consent or refusal to sign the consent form. For the patients: - Previous history of hypersensitivity to gadolinium.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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>35 patients | Diagnostic Test: Echocardiography at T0<br> <br> Diagnostic Test: Exercise test<br> <br> Biological: Biological assays<br>* Creatinin, hematocrit and BNP assays<br>Device: MRI with contrast agent injection<br>* With injection of gadolinium<br>Diagnostic Test: Echocardiography at M24<br> <br> |
| Healthy volunteers<br>20 healthy volunteers | Diagnostic Test: Echocardiography at T0<br> <br> Device: MRI without contrast agent injection<br>* Without injection of gadolinium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular symptoms | Dyspnea, angor, syncope and lipothymia, palpitations, heart failure signs | Baseline | 
| Metabolic exercise test marker : poor blood pressure adaptation to exercise |  | Baseline | 
| Metabolic exercise test marker: max level achieved |  | Baseline | 
| Metabolic exercise test marker : percentage of theoretical maximal heart rate |  | Baseline | 
| Metabolic exercise test marker : peak of Oxygen uptake (VO2) |  | Baseline | 
| Metabolic exercise test marker : percentage of expected peak VO2 |  | Baseline | 
| Metabolic exercise test marker : Expiratory volume / carbon dioxide production (VE/VCO2) |  | Baseline | 
| Biological marker : BNP elevation |  | Baseline | 
| Electrical markers at ECG and Holter ECG | Measure of conduction troubles; supra-ventricular and ventricular arrhythmias. | Baseline |