Amyloidosis TTR Flow Reserve Evaluation

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.

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