Cardiac [99mTc]Tc-hydroxydiphosphonate uptake on bone scintigraphy in patients with hereditary transthyretin amyloidosis: an early follow-up marker?

PURPOSE: There is a need for early quantitative markers of potential treatment response in patients with hereditary transthyretin (ATTRv) amyloidosis to guide therapy. This study aims to evaluate changes in cardiac tracer uptake on bone scintigraphy in ATTRv amyloidosis patients on different treatments. METHODS: In this retrospective cohort study, outcomes of 20 patients treated with the transthyretin (TTR) gene silencer patisiran were compared to 12 patients treated with a TTR-stabilizer. Changes in NYHA class, cardiac biomarkers in serum, wall thickness, and diastolic parameters on echocardiography and NYHA class during treatment were evaluated. RESULTS: Median heart/whole-body (H/WB) ratio on bone scintigraphy decreased from 4.84 [4.00 to 5.31] to 4.16 [3.66 to 4.81] (p < .001) in patients treated with patisiran for 29 [15-34] months. No changes in the other follow-up parameters were observed. In patients treated with a TTR-stabilizer for 24 [20 to 30] months, H/WB ratio increased from 4.46 [3.24 to 5.13] to 4.96 [ 3.39 to 5.80] (p = .010), and troponin T increased from 19.5 [9.3 to 34.0] ng/L to 20.0 [11.8 to 47.8] ng/L (p = .025). All other parameters did not change during treatment with a TTR-stabilizer. CONCLUSION: A change in cardiac tracer uptake on bone scintigraphy may be an early marker of treatment-specific response or disease progression in ATTRv amyloidosis patients.

Positron emission tomography in the diagnosis and follow-up of transthyretin amyloid cardiomyopathy patients: A systematic review.

PURPOSE: Transthyretin (ATTR) amyloidosis is a progressive protein misfolding disease with frequent cardiac involvement. This review aims to determine the value of PET in diagnosis, assessment of disease progression or treatment response and its relation to clinical outcome in follow-up of ATTR amyloid cardiomyopathy (ATTR-CM) patients. METHODS: Medline, Cochrane Library, Embase and Web of Science databases were searched, from the earliest date available until December 2022, for studies investigating the use of PET in ATTR-CM patients. Studies containing original data were included, except for case reports. Risk of bias was assessed by QUADAS-2. RESULTS: Twenty-one studies were included in this systematic review, investigating five different tracers: carbon-11 Pittsburgh compound B ([11C]PIB), fluorine-18 Florbetaben ([18F]FBB), fluorine-18 Florbetapir ([18F]FBP), fluorine-18 Flutemetamol ([18F]FMM) and fluorine-18 Sodium Fluoride (Na[18F]F). In total 211 ATTR amyloidosis patients were included. A majority of studies concluded that [11C]PIB, [18F]FBP and Na[18F]F can distinguish ATTR amyloidosis patients from controls, and that [11C]PIB and Na[18F]F, but not [18F]FBP, can distinguish ATTR-CM patients from patients with cardiac light chain amyloidosis. Evidence on the performance of [18F]FBB and [18F]FMM was contradictory. No studies on the use of PET in follow-up were found. CONCLUSION: [11C]PIB, Na[18F]F and [18F]FBP can be used to diagnose cardiac amyloidosis, although [18F]FBP may not be suitable for the distinction of different types of amyloid cardiomyopathy. No studies on PET in the follow-up of ATTR amyloidosis patients were found. Future research should focus on the use of these PET tracers in the follow-up of ATTR amyloidosis patients.