Myocardium-to-cavity ratio derived from simultaneous 99mTc-PYP/201Tl dual-isotope SPECT imaging to differentially diagnose transthyretin cardiac amyloidosis.

Abstract

Background: The heart-to-contralateral lung (H/CL) ratio, derived from planar imaging, is a standard quantitative metric in ^99mTc-pyrophosphate (^99mTc-PYP) studies. However, cardiac-dedicated cadmium-zinc-telluride cameras, which primarily generate single-photon emission computed tomography (SPECT) images, cannot produce planar images. We propose the myocardium-to-cavity (M/C) ratio, derived from simultaneous dual-isotope ^99mTc-PYP/²⁰¹Tl SPECT imaging, as an alternative quantitative measure. This study evaluates the clinical utility of the M/C ratio by comparing it to the H/CL ratio.

Methods/results: We retrospectively analyzed 121 consecutive patients with suspected cardiac amyloidosis who underwent dual-isotope ^99mTc-PYP/²⁰¹Tl imaging. Anterior planar images were acquired using an Anger camera at 1 h after ^99mTc-PYP injection. Dual-isotope D-SPECT ^99mTc-PYP/²⁰¹Tl images were acquired from 10 min after ²⁰¹Tl injection at 1 and/or 3 h after ^99mTc-PYP injection. For M/C ratio calculation, circular regions of interest of equal diameter were set on the myocardium and left ventricular cavity using ²⁰¹Tl images, then superimposed on ^99mTc-PYP images. The optimal cut-off values were 1.5 for H/CL and 1.0 for M/C ratios to distinguish ^99mTc-PYP positive and negative uptake. Of 121 patients, 19 (16%) were classified as ^99mTc-PYP positive with planar and SPECT imaging, following the stepwise diagnostic flow recommended by the Japanese Society of Nuclear Cardiology (adapted for D-SPECT). Both H/CL and M/C ratios were significantly higher in patients with ^99mTc-PYP-positive than in negative cases. Notably, five false-positive cases with H/CL ratios > 1.5 had M/C ratio < 1.0, correctly distinguishing them from ^99mTc-PYP-positive patients. The M/C ratio demonstrated 100% sensitivity, specificity, and predictive values, irrespective of imaging time. In contrast, the H/CL ratios showed 100% sensitivity, 95% specificity, 79% positive predictive value, and 100% negative predictive value. The inter- and intra-observer reproducibility of the M/C ratio was excellent with correlation coefficients exceeding 0.99. Additionally, 13 of the 19 (68%) ^99mTc-PYP positive patients exhibited a mismatch pattern with decreased ²⁰¹Tl uptake corresponding to high ^99mTc-PYP uptake.

Conclusions: The M/C ratio demonstrated superior diagnostic accuracy compared to the H/CL ratio, particularly in eliminating false positive cases. Its simplicity and reproducibility make it a promising alternative for routine clinical practice, potentially replacing the H/CL ratio in dual-isotope imaging.