Amyloidosis TTR Flow Reserve Evaluation

Study Overview
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Brief Summary
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Anginal symptoms and signs of ischemia have been reported in some patients with cardiac amyloidosis (TTR) without obstructive epicardial coronary artery disease (CAD). It was found that coronary microvascular dysfunction was highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD. The investigators found lower stress and rest myocardial blood flow (MBF) and lower myocardial flow reserve (MFR) in their cardiac PET (Positron emission tomography) study (13N), including 21 patients. The advances in SPECT technology including cadmium zinc telluride (CZT) detectors allow to evaluate the MBF and MFR estimation by SPECT as shown in both experimental animal models and also in clinical studies with comparison to PET. SPECT is more widely available than cardiac PET. Thus, the investigators would like: to confirm the results of Dorbala et al using SPECT, and to go further with evaluation of the effect of Tafamidis on microvascular dysfunction.

Official Title
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Amyloidosis TTR Flow Reserve Evaluation

Conditions
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Amyloid Cardiomyopathy

Intervention / Treatment
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* Other: SPECT MPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged from 18 to 90 years Understanding and speaking French With TTR amyloid cardiomyopathy (ATTRxt or ATTRm) confirmed by the association of heart failure, syncope or bradyarrhythmia, with electrocardiogram and/or magnetic resonance imaging (CMR) suggesting/indicating cardiac amyloid, grade 2 or 3 99mTc- PYP or bone scintigraphy and negative biological findings (i.e. serum immunofixation, urine immunofixation, serum free light chain assay); or, if one of those criteria is not met, presence of amyloid deposits on analysis of biopsy specimens obtained from cardiac and non-cardiac sites (17-19), Intention to treat (Tafamidis) Exclusion Criteria: Heart failure not due to transthyretin amyloid cardiomyopathy; New York Heart Association (NYHA) class IV heart failure. The presence of light-chain amyloidosis; A history of liver or heart transplantation; An estimated glomerular filtration rate lower than 25 mL per minute per 1.73 m2 of bodysurface area (Cockcroft). Liver transaminase levels exceeding two times the upper limit of the normal range; Severe malnutrition as defined by a modified body-mass index (mBMI) of less than 600, calculated as the serum albumin level in grams per litter multiplied by the conventional BMI (the weight in kilograms divided by the square of the height in meters); Patients receiving concurrent treatment with nonsteroidal anti-inflammatory drugs, tauroursodeoxycholate, doxycycline, calcium-channel blockers, or digitalis; Previous treatment with tafamidis or patisaran; Ticagrelor treatment Previous CAD, severe epicardial stenosis with revascularization or ticagrelor treatment, coronary artery bypass grafting, myocardial infarction; Contra-indications to pharmacological stress testing MPI: severe hypotension (< 90 mmHg of Systolic arterial pressure), atrioventricular block 2nd or 3rd grade, carotid stenosis (unilateral >70%, bilateral >50%); Pregnancy Breastfeeding Protected adults Other study participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPECT MPI (myocardial perfusion imaging) Group<br>the SPECT MPI protocol will be modified to evaluated MBF and MFR. This modification will result in no added radiation; the radiopharmaceutical dose will still be the same compared to a standard MPI protocol. | Other: SPECT MPI<br>* SPECT MPI including dynamic acquisitions for stress, rest MBF and MFR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of Stress and Rest Myocardial Blood Flow | Difference of Stress and Rest Myocardial Blood Flow (mL/min/g) at baseline and after 24 months of treatments, assessed by dynamic SPECT (regional and global left ventricle measurements) | Month 24 | 
| ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow | Difference of Myocardial Flow Reserve (ie ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow) at baseline and after 24 months of treatments, assessed by dynamic SPECT (regional and global left ventricle measurements) | Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number or participants with stress reduction | Stress assessed by dynamic SPECT (regional and global left ventricle measurements), in comparison to normal values | baseline | 
| Number or participants with rest MBF (myocardial blood flow) reduction | Rest Myocardial Blood Flow (mL/min/g) assessed by dynamic SPECT (regional and global left ventricle measurements), in comparison to normal values | baseline | 
| ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow | Myocardial Flow Reserve (ie ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow) assessed by dynamic SPECT (regional and global left ventricle measurements) in comparison to normal values | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tafamidis