Technetium Tc 99m PYP Scanning for TTR Cardiac Amyloidosis
- Noninvasive testing is increasingly used for the initial workup of ATTR-CA and has favorable test characteristics compared with biopsy results.
- A significant number of patients in this cohort did not have recommended monoclonal protein evaluation to rule out AL amyloidosis nor genetic testing for TTR mutations.
- 99mTc-PYP scanning that is visual score grade 2 with planar imaging alone is often a false-positive result and the addition of SPECT to positive planar scanning is indicated to prevent misdiagnosis.
What are the trends in technetium Tc 99m pyrophosphate (99mTc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, appropriateness of assessment with monoclonal protein and genetic testing, use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and predictive factors for ATTR-CA?
The investigators analyzed patients undergoing 99mTc-PYP scanning 1 hour after injection at a quaternary care center from 2010–2019, abstracted clinical information, and analyzed SPECT results. Patients were diagnosed with ATTR-CA by either histology with positive cardiac biopsy for ATTR-CA or by imaging criteria that included all of the following criteria: 1) echocardiography or cardiac magnetic resonance findings with increased left ventricular wall thickness consistent with ATTR-CA, 2) grade 2 or 3 cardiac scintigraphy with 99mTc-PYP, and 3) negative monoclonal protein testing with negative serum protein electrophoresis and serum free light chains. 99mTc-PYP scan test characteristics including sensitivity and specificity were calculated using 2 × 2 tables against the reference standard of cardiac biopsy.
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 three 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.
The authors concluded that 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.
This single-center study reports that noninvasive testing is increasingly used for the initial workup of ATTR-CA and has favorable test characteristics compared with biopsy results. However, a significant number of patients in this cohort did not have recommended monoclonal protein evaluation to rule out AL amyloidosis nor genetic testing for TTR mutations. In fact, 99mTc-PYP scanning that is visual score grade 2 with planar imaging alone is often a false-positive result and the addition of SPECT to positive planar scanning is indicated to prevent misdiagnosis. Additional studies are indicated to optimize, prospectively validate, and develop predictive models that can accurately identify early cases of cardiac amyloidosis with the greatest likelihood of impact on altering the natural history of this disease.
Keywords: Amyloidosis, Diagnostic Imaging, Echocardiography, Electrophoresis, Genetic Testing, Genes, Immunoglobulin Light Chain, Geriatrics, Heart Failure, Magnetic Resonance Spectroscopy, Mutation, Prealbumin, Radionuclide Imaging, Secondary Prevention, Technetium, Technetium Tc 99m Pyrophosphate, Tomography, Emission-Computed, Single-Photon
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