Impact of MIgalastat TheRApy on CaRdiac Function in patiEnts With Fabry's Cardiomyopathy (MIRACRE-Fabry Trial)

Study Overview
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Brief Summary
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This is an observational study. No treatment or intervention will be assigned to the subjects. All patients will receive full standard of care concomitant medication for the treatment of their cardiac condition. 20 patients with genetically confirmed Anderson-Fabry disease who have a plan to start Migalastat will undergo 2D strain, diastolic stress echocardiography, LV vortex flow analysis, and CMR at baseline and after 2 year of treatment with Migalastat for follow-up.

Detailed Description
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Objectives - to evaluate the impact of chaperone therapy on LV diastolic function and flow in patients with Fabry's cardiomyopathy using LV 2D strain, diastolic stress echocardiography, LV vortex flow and CMR. Primary/Secondary Endpoint A. Primary endpoint: - Change of peak exercise E/E' by diastolic stress echocardiography, global longitudinal strain and LV vortex flow parameters at 2 year follow up. B. Secondary endpoints: Changes of extracellular volume by CMR (T1 mapping) at 2 year follow up Evaluation of the degree of the resting LV diastolic function Evaluation of global and regional LV strain Other echo-parameters; LV mass index at baseline, 2 year follow up, reduction of peak exercise E/E prime at 2 year follow up Changes of quality of life using questionnaire Change of peak VO2, exercise time, AT by diastolic stress echocardiography at 2 year follow up Change in T1 baseline (myo, ms) & T1 baseline (blood, ms) T1 postcontrast (myo, ms) & T1 baseline (blood, ms) by CMR Study Methods -Study Design: This is an observational study. No treatment or intervention will be assigned to the subjects. All patients will receive full standard of care concomitant medication for the treatment of their cardiac condition. 20 patients with genetically confirmed Anderson-Fabry disease who have a plan to start Migalastat will undergo 2D strain, diastolic stress echocardiography, LV vortex flow analysis, and CMR at baseline and after 2 year of treatment with Migalastat for follow-up.

Official Title
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Impact of MIgalastat TheRApy on CaRdiac Function in patiEnts With Fabry's Cardiomyopathy (MIRACRE-Fabry Trial)

Conditions
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Fabry Disease

Intervention / Treatment
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* Other: Echocardiography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 16   70 years with Fabry's disease who were confirmed by enzyme assay and gene study Patients who have LV hypertrophy in 2D echocardiography (end diastolic septum and posterior wall thickness ≥12mm) or Patients who present with cardiac changes (indicative of disease progression such as decreased global longitudinal strain on 2D strain echocardiography or low native T1 mapping on cardiac MRI) even without LV wall thickness of ≥12mm Patients provided with the written, informed consent to participate in this study Exclusion Criteria: Contraindication for chaperone therapy (Migalastat) Patients who cannot perform supine bicycle stress echocardiography, contrast echocardiography or cardiac MRI Hemodynamically significant valvular heart disease or arrythmias History of acute myocardial infarction or congestive heart failure with reduced LV ejection fraction of less than 35% CVA in the prior 6 months Scheduled or planned surgery in the next 6 months Chronic liver cirrhosis Allergy to contrast agent (Definity®, Lantheus Medical Imaging, North Billerica, MA, USA)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 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 |
| --- | --- |
| Fabry's disease<br>Fabry's disease patients who were confirmed by enzyme assay and gene study | Other: Echocardiography<br>* LV vortex flow in Echocardiography<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of peak exercise E/E' by diastolic stress echocardiography |  | 2 years | 
| Change of global longitudinal strain |  | 2 years | 
| Change of LV vortex flow parameters |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of extracellular volume by CMR (T1 mapping) |  | 2 years | 
| Evaluation of the degree of the resting LV diastolic function |  | 2 years | 
| Evaluation of global and regional LV strain |  | 2 years | 
| Evaluation of LV mass index |  | 2 years | 
| Evaluation of reduction of peak exercise E/E prime |  | 2 years | 
| Changes of quality of life using Short Form 36 |  | 2 years | 
| Change of peak VO2 by diastolic stress echocardiography |  | 2 years | 
| Change of exercise time by diastolic stress echocardiography |  | 2 years | 
| Change of AT by diastolic stress echocardiography |  | 2 years | 
| Change in T1 baseline (myo, ms) & T1 baseline (blood, ms) T1 postcontrast (myo, ms) & T1 baseline (blood, ms) by CMR |  | 2 years |