A new prospective, case-control study will investigate the use of 18F-fluoride positron emission tomography (PET) for monitoring tafamidis treatment response in patients with cardiomyopathy associated with hereditary transthyretin amyloidosis (hATTR). The study is currently recruiting.
The researchers plan to enroll 140 participants with cardiac hATTR, cardiac light chain amyloidosis, or hypertrophic cardiomyopathy. All patients must be over 40 years of age, except those with hypertrophic cardiomyopathy, who must be over 30.
The exclusion criteria prohibit women who are pregnant, breastfeeding, or of childbearing potential from entering the study, as well as people with renal dysfunction, NYHA class IV heart failure, atrial fibrillation, or poor rate control, contraindications to magnetic resonance imaging, or previous history of contrast allergy or adverse reactions to gadolinium.
The primary outcome measure is evaluating the myocardial tissue to background ratio (TBR) threshold after 1.5 years of study duration.
Read more about hATTR testing
The researchers will also monitor changes in TBR, TBR threshold specificity and sensitivity, cardiac indices on cardiovascular magnetic resonance imaging such as left ventricular ejection fraction, left ventricular mass, extracellular volume, and left ventricular global longitudinal strain, cardiac biomarkers such as NT-ProBNP and troponin I, as well as clinical measures such as 6-minute walk test and KCCQ score after 2.5 years as secondary outcome measures.
January 30, 2024, is reported as both the estimated primary completion date and the estimated study completion date.
According to the study protocol, the researchers will first optimize 18F-fluoride PET imaging of TBR uptake values in 15 participants with cardiac hATTR. In 100 participants with cardiac hATTR, 20 with light chain amyloidosis, and 20 with hypertrophic cardiomyopathy, they will identify the optimized 18F-fluoride TBR threshold that best differentiates hATTR cardiomyopathy from phenocopies.
Next, the study authors will perform an in vivo calibration of 18F-fluoride PET as a marker of the myocardial hATTR burden in 100 participants. The optimized TBR values will be adjusted against the current imaging standard, cardiovascular magnetic resonance imaging extracellular volume. Lastly, the ability of 18F-fluoride PET to track disease progression and treatment response in cardiac hATTR at 1-year follow-up will be assessed.
The mechanism of calcium deposition in the heart muscle of people with cardiac hATTR is not clear, along with the mechanism of action of tafamidis. The researchers hypothesize that 18F-fluoride PET might become a useful tool in understanding these phenomena, diagnosing hATTR, and tracking the disease progression as well as tafamidis treatment effectiveness.
Quantitative-imaging in cardiac transthyretin amyloidosis (I-CARE). ClinicalTrials.gov. March 20, 2023. Updated March 20, 2023. Accessed March 21, 2023.