Biomarkers to Predict Abnormal Technetium-99m Pyrophosphate Scans in Patients With Suspected Transthyretin Amyloidosis

Laura De Michieli; Omar F AbouEzzeddine; Muhannad A Abbasi; Daniel R Davies; Christopher G Scott; Eli Muchtar; Angela Dispenzieri; Martha Grogan; Margaret M Redfield; Allan S Jaffe

doi:10.1016/j.jaccao.2024.10.013

Biomarkers to Predict Abnormal Technetium-99m Pyrophosphate Scans in Patients With Suspected Transthyretin Amyloidosis

JACC CardioOncol. 2025 Jan 21;7(1):70-78. doi: 10.1016/j.jaccao.2024.10.013. eCollection 2025 Jan.

Authors

Affiliations

¹ Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
² Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
³ Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
⁴ Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

Abstract

Background: Technetium Tc 99m pyrophosphate scintigraphy (^99mTc PYP imaging) is a diagnostic tool for transthyretin amyloid cardiomyopathy (ATTR-CM). Cardiac biomarkers, particularly high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), may help identify patients at low or high risk for ATTR-CM.

Objectives: The authors sought to evaluate the predictive value of hs-cTnT and NT-proBNP in patients undergoing ^99mTc PYP imaging for suspected ATTR-CM in a large U.S. cohort.

Methods: This was a retrospective study of patients who underwent ^99mTc PYP imaging between May 2013 and September 2022, including those with at least 1 hs-cTnT measurement within 6 months of the scan.

Results: ATTR-CM was diagnosed in 427 of 1,442 patients (29.6%). A hs-cTnT level <6 ng/L (n = 50, 3.5%) showed a negative predictive value of 100% (95% CI: 93%-100%) and sensitivity of 100% (95% CI: 99%-100%) for ruling out ATTR-CM. As the hs-cTnT threshold increased, the number of patients who could be ruled out also increased, but false negatives emerged. The positive predictive value for ruling in ATTR-CM remained low. NT-proBNP showed similar results (n = 1,378). The combination of hs-cTnT <14 ng/L and NT-proBNP <60 ng/L identified 45 patients (3.3%) without ATTR-CM.

Conclusions: In patients undergoing ^99mTc PYP imaging for suspected ATTR-CM, very low hs-cTnT levels can effectively rule out the diagnosis, although in a small subset of patients. Higher thresholds increase the risk of false negatives. NT-proBNP and combined biomarker strategies showed similar trends, the utility of hs-cTnT and NT-proBNP for ruling in the disease is limited.

Keywords: amyloidosis; biomarkers; cardiac troponin; cardiomyopathy; diagnostic performance; transthyretin amyloid cardiomyopathy.