Background: Cardiac transthyretin amyloidosis (ATTR-CA) is a chronic debilitating disease with high mortality. The transthyretin stabilizer tafamidis inhibits de-novo amyloidogenesis, halts disease progression and reduces all-cause mortality. To date, there are no specific biomarkers to assess disease activity and response to treatment. The aim of the study was to evaluate potential changes in bone tracer uptake by the myocardium in patients under tafamidis treatment.

Methods: Patients with ATTR-CA on long-term tafamidis treatment who had undergone bone scintigraphy prior to treatment initiation and after at least one year after treatment initiation were eligible for the study. All study patients received ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) scintigraphy and multiparametric disease assessment, including echocardiography and serum biomarkers. Tracer activity was assessed visually according to the Perugini grading scale, by calculation of the heart to contralateral lung (H/CL) ratio, myocardium to blood pool (MBR) and vertebral bone ratios (MVR) as well as by absolute quantification of myocardial  ^99mTc- DPD uptake as maximal standardized uptake values (SUVmax).

Results: The study included 14 patients who received tafamidis for 44 ± 14 months. We observed stable or improving NYHA Class in all but 3 patients. Our analysis showed regression of Perugini Grade in 5 and unchanged grade in 9 patients, regression of H/CL ratio (2.2 vs 1.8, p = 0.015), MBRmax (8.5 vs 5.2, p =0.029), MVRmax  (1.9 vs 1.1, p = 0.038 ) and SUVmax (11.9 vs 7.5, p = 0.005). There were no significant changes in NT-proBNP (4872 vs 3919 pg/ml, p = 0.24 ), eGFR (62.7 vs 57.1 ml/min/1.73m², p = 0.1), and multiple echocardiographic measures including left ventricular global longitudinal strain (mean delta: +1%, -11.9 vs -10.9 %, p =0.29 ) and ejection fraction (mean delta: -2.8%, 53.0 vs 50.2%, p = 0.08). There was no correlation between absolute changes in laboratory and echocardiographic parameters and H/CL ratio or SUVmax.

Conclusions: Treatment with tafamidis results in regression of myocardial  ^99mTc-DPD uptake indicating that this pharmacologic intervention not only inhibits de-novo amyloidogenesis but may also result in a decrease of myocardial amyloid load.  ^99mTc-DPD scintigraphy may serve as a useful, independent biomarker of response to treatment.