Diagnosing Transthyretin Cardiac Amyloidosis by Technetium Tc 99m Pyrophosphate: A Test in Evolution

Objectives: This study aimed to characterize trends in technetium Tc 99m pyrophosphate (^99mTc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, to determine whether patients underwent appropriate assessment with monoclonal protein and genetic testing, to evaluate use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and to identify predictive factors for ATTR-CA.

Background: ^99mTc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA. Increasing use of ^99mTc-PYP can facilitate identification of ATTR-CA, but appropriate use is critical for accurate diagnosis in an era of high-cost targeted therapeutics.

Methods: Patients undergoing ^99mTc-PYP scanning 1 h after injection at a quaternary care center from 2010 to 2019 were analyzed; clinical information was abstracted; and SPECT results were analyzed.

Results: Over the decade, endomyocardial biopsy rates remained stable with scanning rates peaking at 132 in 2019 (p < 0.001). Among 753 patients (516 men, mean age 77 years), 307 (41%) had a visual score of 0, 177 (23%) of 1, and 269 (36%) of 2 or 3. Of 751 patients with analyzable heart to contralateral chest ratios, 249 (33%) had a ratio ≥1.5. Monoclonal protein testing status was assessed in 550 patients, of these, 174 (32%) did not undergo both serum immunofixation and serum free light chain analysis tests, and 331 (60%) did not undergo all 3 tests-serum immunofixation, serum free light chain analysis, and urine protein electrophoresis. Of 196 patients with confirmed ATTR-CA, 143 (73%) had genetic testing for transthyretin mutations. In 103 patients undergoing cardiac biopsy, grades 2 and 3 99mTc-PYP had sensitivity of 94% and specificity of 89% for ATTR-CA with 100% specificity for grade 3 scans. With respect to SPECT as a reference standard, planar imaging had false positive results in 16 of 25 (64%) grade 2 scans.

Conclusions: Use of noninvasive testing with ^99mTc-PYP scanning for evaluation of ATTR-CA is increasing, and the inclusion of monoclonal protein testing and SPECT imaging is crucial to rule out amyloid light chain amyloidosis and distinguish myocardial retention from blood pooling.