Diagnostic utility of semi-quantitative planar scintigraphy in ATTR cardiac amyloidosis: timepoint analysis and extracardiac tracer distribution

Technetium-99m-pyrophosphate (99mTc-PYP) planar scintigraphy, a core modality of cardiac amyloid radionuclide imaging (CARI), is a widely established noninvasive technique for diagnosing transthyretin cardiac amyloidosis (ATTR-CA). However, the diagnostic contribution of semi-quantitative uptake indices and extracardiac tracer distribution remains incompletely defined. To evaluate the diagnostic performance of semi-quantitative planar 99mTc-PYP scintigraphy in patients with suspected ATTR-CA, including analysis of extracardiac uptake and temporal stability. In this retrospective study, 174 consecutive patients referred for 99mTc-PYP scintigraphy were analyzed. Inclusion was based on heart failure symptoms and echocardiographic findings suggestive of CA (e.g., wall thickness ≥ 12 mm). Heart-to-contralateral lung (H/CL) and heart-to-mediastinum (H/M) ratios were measured from anterior and left-lateral planar images at 1 and 3 h post-injection. Extracardiac tracer uptake was quantified using soft tissue-to-rib ratios at shoulder, elbow, axilla, and liver sites. Final diagnosis was determined by histopathology and/or validated non-biopsy clinical criteria. H/CL and H/M ratios demonstrated excellent diagnostic performance for identifying ATTR-CA, with AUCs of 0.97 and 0.88, respectively (0.98 and 0.93 in the histologically confirmed subgroup). Both indices were strongly correlated (r > 0.8). H/M values were stable across timepoints (p = 0.22), while H/CL showed a slight but statistically significant decline (1.4 vs. 1.3, p = 0.01). Patients with confirmed ATTR-CA had significantly higher myocardial and selected extracardiac uptake ratios (e.g., elbow/rib, axilla/rib) compared with non-ATTR individuals (p < 0.05). Semi-quantitative 99mTc-PYP planar scintigraphy provides high diagnostic accuracy for ATTR-CA, with the 1-h H/CL ratio showing the highest performance. Lateral H/M projections offer stable measures that improve confidence in cases with sternal overlap. While extracardiac uptake reflects systemic involvement, it currently serves as a hypothesis-generating marker. Incorporating these semi-quantitative metrics into routine workflows supports objective, clinically actionable assessment and may reduce the need for invasive histological confirmation.