Key result
None of the patients with equivocal grade 1 Tc-99m-PYP scans were diagnosed with ATTR-CM, and they exhibited distinct echocardiographic features compared to those with positive scans.
Why the study?
The clinical significance of grade 1 (equivocal) Technetium-99m-pyrophosphate bone scintigraphy scans for transthyretin cardiac amyloidosis is unclear.
Does an equivocal Tc-99m-PYP scan correlate with a clinical diagnosis of ATTR-CM compared to positive scans?
Cohort (n=155)
Yes
Does an equivocal Tc-99m-PYP scan correlate with a clinical diagnosis of ATTR-CM compared to positive scans?
Equivocal Tc-99m-PYP scans are generally not associated with an ATTR-CM diagnosis and warrant further definitive workup to distinguish early disease from false positives.
Equivocal Tc-99m-PYP scans were not associated with ATTR-CM; leaves open the need for confirmatory testing in grade 1 cases.
Background: Transthyretin cardiac amyloidosis (ATTR-CM) is an underdiagnosed infiltrative cardiomyopathy. Diagnosis is based on Technetium-99m-pyrophosphate-bone-scintigraphy scans (Tc-99m-PYP) with grades 2 to 3 classified as positive. The clinical significance of grade 1 (classified equivocal by American Society of Nuclear Cardiology) is unclear. We aimed to describe the differences in clinical/imaging characteristics among those with equivocal vs positive Tc-99m-PYP and to describe outcomes of further investigations. Methods: We performed a retrospective study of patients who underwent Tc-99m-PYP at 2 institutions between January 2017 and November 2022. Baseline demographics, laboratory, and imaging data were collected. Results: A total of 502 Tc-99m-PYP were performed with single-photon emission computed tomography (SPECT) 3 hours post-tracer injection: 347 (69%) negative, 46 (9%) equivocal, and 109 (22%) positive. In the latter 2 groups, the median age was 78 (interquartile range [IQR]: 72-84) years, and 38 (25%) were female. Average follow-up was 19.7 ± 14.6 months. No patients with equivocal scans were diagnosed with ATTR-CM. Equivocal scans had lower intraventricular septal diameters (11 mm [IQR: 10-11] vs 15 mm [IQR: 12-17]), larger left ventricular end-diastolic dimension (50 mm [IQR: 44-56] vs 43 mm [IQR: 40-50]), and more negative global longitudinal strain (-18.7 [IQR: -22.2 to -18.7] vs -13.8 [IQR: -17.9 to -10.9] %). Only 12 (26%) patients with equivocal scans underwent further imaging or biopsy. Of 2 patients with monoclonal gammopathy, 1 had AL-amyloidosis. Conclusions: Our patients with equivocal grade 1 scans were not diagnosed with ATTR-CM. They exhibited distinct imaging compared to positive scans. Our findings suggest that ATTR-CM phenotype and equivocal scans may represent early ATTR-CM (ie, false negative) or false positives and should undergo further workup. Further research is needed to determine the significance of equivocal studies.
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Chai et al. (2025) conducted a cohort in Transthyretin Amyloid Cardiomyopathy (ATTR-CM) (n=155). Equivocal (grade 1) Tc-99m-PYP scan vs. Positive (grade 2 or 3) Tc-99m-PYP scan was evaluated on Diagnosis of ATTR-CM. None of the patients with equivocal grade 1 Tc-99m-PYP scans were diagnosed with ATTR-CM, and they exhibited distinct echocardiographic features compared to those with positive scans.
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