A quantitative SPECT/CT metric for diagnosing transthyretin cardiac amyloidosis: multicenter study on biopsy-confirmed cases.

Abstract

99mTechnetium-pyrophosphate ([^99mTc]Tc-PYP) scintigraphy is the gold standard for diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM). Conventional metrics, such as heart-to-contralateral-chest (H/CL) ratio and visual Perugini score, can be influenced by physiological blood pool uptake, leading to false positives and additional patient burdens. This study aimed to develop and validate a simple quantitative metric widely applicable for ATTR-CM diagnosis. This multicenter retrospective study enrolled 253 patients who underwent [^99mTc]Tc-PYP SPECT/CT between April 2021 and September 2024. SPECT/CTs were acquired 3 h post-injection of 740 MBq [^99mTc]Tc-PYP. A lateral wall-to-aorta (LW/Ao) ratio was obtained by dividing the average radiotracer count in the lateral wall of the left ventricle by the average count in the ascending aorta. The diagnosis of ATTR-CM diagnosis was determined by endomyocardial biopsy. As statistical analyses, area under receiver operating characteristic (AUC) was used to compare diagnostic accuracy, and intraclass correlation coefficient (ICC) was used to assess inter-rater agreement. Among 52 patients (31 men; mean age 77) whose biopsy results were available, 11 were diagnosed with ATTR-CM. LW/Ao ratio showed a sensitivity of 100% (11/11), specificity of 97.6% (40/41), and positive likelihood ratio of 41.0. LW/Ao ratio showed higher AUC (0.99; 95% CI: 0.99-1.00) compared to H/CL ratio (AUC = 0.90, p = 0.04) and visual score (AUC = 0.87, p < 0.01). The ICC of LW/Ao ratio was excellent (0.91 ≥ 0.9). The quantitative SPECT/CT metric demonstrated superior diagnostic accuracy for ATTR-CM compared to conventional methods.