Can 99mTc-DPD scintigraphy track tafamidis response in hATTR cardiac amyloidosis?

Abstract Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a major cause of heart failure, due to improved awareness of red flags and growing use of non-invasive tests such as 99mTC-DPD bone scintigraphy. The emergence of disease-modifying therapies (DMT), particularly tafamidis, have significantly altered the natural history of ATTR-CM and highlighted the need for reliable methods to assess treatment response. However, the ability of imaging modalities to reflect changes in amyloid burden during therapy and track disease progression is not fully established. Aims To evaluate disease progression in hATTR-CM patients treated with tafamidis and to assess the utility of 99mTC-DPD in monitoring treatment response. Methods Single-center, retrospective study including consecutive patients diagnosed with hATTR-CM between 2022 and 2025. Clinical, laboratory, and echocardiographic data were collected at baseline and follow-up. Pre and post-treatment 99mTC-DPD bone scintigraphy was performed and Perugini scores were compared and correlated with disease progression and clinical outcomes. Results A total of 48 patients with hATTR-CM were included (mean age 69±1.7 years, 33 (83%) male). Genetic variants included: Val30Met in 41 patients (85%), G89L in 1 patient (2%) and V122L in 6 patients (13%). Hypertension was present in 28 patients (58%), followed by atrial fibrillation in 11 (23%). At baseline, 34 patients (71%) had a positive 99mTC-DPD bone scintigraphy. Patients with a Perugin Score of 0-1 underwent endomyocardial biopsy for diagnostic confirmation. All patients were treated with tafamidis 61 mg. Over a mean follow-up of 36±3 months, 11 patients (23%) experienced heart failure decompensation, 5 (10%) required cardiovascular hospitalization and 4 (8%) died, including 1 confirmed cardiovascular death. Echocardiographic parameters remained stable, with no significant changes between baseline and follow-up. Serum transthyretin (sTTR) levels increased significantly (24±2 to 29±1 mg/dL; p=0.002). Ongoing disease progression despite tafamidis prompted treatment escalation to vutrisiran in 5 patients (10%), with a mean time to switch of 27±6 months. A total of 23 patients underwent follow-up 99mTC-DPD bone scintigraphy at 27±2 months after treatment initiation: 13 patients (57%) showed reduced cardiac uptake, whereas 4 patients (17%) showed increased uptake. No significant differences were observed between these groups regarding functional class, laboratory values, echocardiographic parameters, or outcomes. Conclusion Despite showing that the hATTR-CM patients treated with tafamidis had a reduction in myocardial uptake, our study shows a poor correlation between changes in uptake at follow-up and disease progression/clinical outcomes, possibly limited to the low number of bone scintigraphy at follow-up. Therefore, the utility of bone scintigraphy in assessing treatment response should be interpreted with caution.For image description, please refer to the figure legend and surrounding text.