Microcalcification and 99mTc-Pyrophosphate Uptake without Increased Bone Metabolism in Cardiac Tissue from Patients with Transthyretin Cardiac Amyloidosis

Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by high Tc-99m-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined Tc-99m-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of Tc-99m-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation.

Automated summary

Transthyretin cardiac amyloidosis (ATTR-CA) is associated with high uptake of Tc-99m-labeled bone tracer in the heart. However, the mechanism behind this uptake remains uncertain. This study compared Tc-99m-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) patients. The results showed significantly higher uptake of Tc-99m-PYP in the hearts of ATTR-CA patients compared to AL-CA and non-CA patients. The ATTR-CA tissue had a higher percentage of von Kossa-positive microparticles, indicating calcification. However, there was no upregulation of bone metabolism-related genes in the ATTR-CA samples. Further investigation is needed to understand the mechanism of bone tracer uptake in the heart.