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

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.