2025 Update Consensus of 99mTc-Pyrophosphate Scintigraphy in the Transthyretin Cardiac Amyloidosis from the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China

Abstract

This 2025 updated consensus outlines the diagnostic strategy for transthyretin amyloid cardiomyopathy (ATTR-CM). Given that ATTR-CM is a significant contributor to heart failure, this article emphasizes the importance of making an early and precise diagnosis, particularly as new therapeutic options become available. Highlighting the critical importance of an early and accurate diagnosis, particularly in light of emerging therapeutic modalities, this consensus underscores the central role of ^99mTc-pyrophosphate (PYP) scintigraphy as a non-invasive diagnostic tool. The consensus calls for the adoption of standardized imaging protocols and interpretation criteria to ensure consistency and reliability across diverse clinical settings. The integration of qualitative and quantitative imaging techniques within a structured diagnostic framework places particular focus on the use of single-photon emission computed tomography/computed tomography (SPECT/CT) imaging to enhance diagnostic precision by minimizing blood pool activity and eliminating overlapping interference. Three-hour imaging is considered to be critical for accurate evaluations and to reduce false-positive findings, and it is recommended for its superior diagnostic accuracy. Moreover, quantitative assessments are also considered to be essential for evaluating myocardial amyloid deposition. This updated consensus provides comprehensive guidelines for clinicians, with the aim of optimizing patient outcomes through precise diagnosis and effective management of ATTR-CM. The consensus concludes by advocating for continued research and refinement of imaging methodologies, particularly to enhance the clinical applicability of ^99mTc-PYP scintigraphy and other future developments in nuclear molecular imaging.

Keywords: 99mTc-pyrophosphate (PYP) scintigraphy; Cardiac amyloidosis; Heart failure; Standardized uptake value (SUV) quantification; Transthyretin amyloid cardiomyopathy (ATTR-CM).

Central Illustration

Key advances in the early diagnosis and treatment of cardiac amyloidosis, highlighting the role of ^99mTc-PYP scan in diagnostic accuracy and treatment monitoring. ATTR-CM, transthyretin cardiac amyloidosis; CMR, cardiac magnetic resonance; H/CL, heart-to-contralateral lung; PYP, pyrophosphate; SPECT/CT, single-photon emission computed tomography/computed tomography; SUV, standardized uptake value; TTR, transthyretin; UCG, echocardiogram.

Figure 1

The current proposed diagnostic algorithm of suspected cardiac amyloidosis in Taiwan. AL-CM, amyloid light-chain cardiac amyloidosis (AL-CA); ATTR-CM, transthyretin amyloid cardiomyopathy; ATTRv, variant transthyretin amyloidosis; ATTRwt, wild-type transthyretin amyloidosis; CMR, cardiac magnetic resonance; EMB, endomyocardial biopsy; H/CL ratio, heart-to-contralateral lung ratio; PYP, pyrophosphate; SPECT/CT, single-photon emission computed tomography/computed tomography.

Figure 2

Determining the region of interest (ROI) for the quantitation of cardiac ^99mTc-Pyrophosphate (PYP) uptake. (A) The H/CL ratio involves carefully selecting the area of the heart on the planar image. (B) The 1-hour planar image with an H/CL ratio of 1.99 and (C) the 3-hour image with an H/CL ratio of 1.92 show mild washout at a late time point, both in visualization and quantitation. The images courtesy of the Department of Nuclear Medicine, Far Eastern Memorial Hospital. H/CL, heart-to-contralateral lung.

Figure 3

Single-photon emission computed tomography/computed tomography (SPECT/CT) and further quantitative analysis add sensitivity and accuracy. (A) The planar image shows overlapping activity in the myocardium and blood pool, whereas (B) SPECT/CT shows a clearer view. (C) SPECT/CT with the volume of interest (VOI) for the myocardium (red line) and reference areas (dark green line: vertebra, yellow line: para-spinal muscle) provides standard uptake value quantitation indices. (D) Volumetric heart-to-lung ratio with segmentation contouring of the bilateral lungs (light green line) and myocardium (red line).