Volumetric evaluation of 99mTc-pyrophosphate SPECT/CT for transthyretin cardiac amyloidosis: Methodology and correlation with cardiac functional parameters

doi:10.1007/s12350-021-02857-7

Journal of Nuclear Cardiology

Volume 29, Issue 6, December 2022, Pages 3102-3110

https://doi.org/10.1007/s12350-021-02857-7 Get rights and content

Abstract

Background

Volumetric evaluation of ^99mTechnetium-pyrophosphate (^99mTc-PYP) SPECT/CT is a useful method for assessing transthyretin cardiac amyloidosis (ATTR-CA). We investigated the methodology and assessed its relationship with conventional parameters.

Methods and Results

We retrospectively evaluated ^99mTc-PYP SPECT/CT scans of 25 patients who underwent endomyocardial biopsy and/or gene testing. Fourteen (56%) patients were diagnosed with ATTR-CA. SPECT/CT images were acquired at 3 hours after injection. Total volumes of the myocardial regions where uptakes were > 1.2 and 1.4 × aortic blood pool SUVmax were evaluated and defined as cardiac pyrophosphate volume (CPV1.2 and CPV1.4). The heart-to-contralateral lung (H/CL) ratio and myocardial SUVmax were also calculated. CPV1.2 achieved the highest sensitivity and specificity in diagnosing ATTR-CA. In patients diagnosed with ATTR-CA (n = 14), CPV1.2 negatively correlated with left ventricular ejection fraction and positively correlated with left ventricular posterior wall thickness and QRS duration. The correlation was stronger in CPV1.2 than in the H/CL ratio and SUVmax.

Conclusion

Volumetric evaluation of ^99mTc-PYP SPECT/CT may be superior to the H/CL ratio and SUVmax in assessing the disease burden of ATTR-CA. Larger studies are warranted to clarify whether volumetric measurement can assess prognosis and disease progression.

Introduction

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized, progressive, and fatal cardiomyopathy.¹ Autopsy studies have found cardiac ATTR amyloid deposition in up to 25% of individuals over 80 years of age.² Bone scintigraphy using ^99mTechnetium-pyrophosphate (^99mTc-PYP), ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, or ^99mTc-hydroxymethylene diphosphonate is a useful non-invasive examination for the diagnosis of ATTR-CA. A large multicenter study demonstrated that in patients who had undergone serum and urine laboratory tests to exclude light-chain cardiac amyloidosis, bone scintigraphy enables the diagnosis of ATTR-CA with high specificity without invasive biopsy.³

Because of the recent introduction of life-prolonging drugs for ATTR-CA, there is a major unmet need for the early detection and precise quantitative assessment of disease burden, progression, and treatment response.⁴ A multicenter study reported that planar heart-to-contralateral lung (H/CL) ratio of ^99mTc-PYP uptakes had prognostic information.⁵ However, the H/CL ratio is based on two-dimensional imaging and has some inherent limitations, such as influences of blood pool and rib uptakes.⁶ Volumetric evaluation of bone scintigraphy with single-photon emission computed tomography/computed tomography (SPECT/CT) is an objective and quantitative method to overcome weaknesses of conventional methods.⁷^,⁸ The volume of the myocardial region with abnormal uptake is expected to assess disease burden and has a close association with cardiac functional parameters. However, the methodology and characteristics of volumetric parameters have not been fully investigated in patients with ATTR-CA. The aim of this study was to investigate the methodology of volumetric evaluation of ^99mTc-PYP SPECT/CT and to assess its correlation with cardiac functional parameters and other quantitative uptake parameters.

Section snippets

Study Population

We retrospectively evaluated patients who underwent ^99mTc-PYP SPECT/CT for suspected ATTR-CA at our hospital between October 2018 and June 2020. Among them, only patients who underwent endomyocardial biopsy (EMB) and/or TTR gene testing were included. Diagnosis criteria of ATTR-CA were based on one or more of the following: (1) EMB positive for ATTR or (2) documented TTR genetic mutation and evidence of cardiomyopathy without evidence of plasma cell dyscrasia (serum and urine immunofixation and

Patient Population

In total, 25 patients were included with a mean age of 70.4 ± 12.8 years and 15 (60%) males. Population characteristics are summarized in Table 1. Fourteen (56%) patients were diagnosed with ATTR-CA, including hereditary type (ATTRv-CA, n = 9) and wild type (ATTRwt-CA, n = 5). Among patients diagnosed with ATTRv-CA, 8 (89%) patients had Val30Met [p.V50M] mutation and 1 (11%) patient had Leu58Arg [p.L78A] mutation. Eleven (44%) patients were diagnosed with no ATTR-CA and used as control

Discussion

This study suggests two important points. First, CPV1.2 was superior to CPV1.4 and the H/CL ratio in diagnosing ATTR-CA. Second, CPV1.2 was superior to the H/CL ratio and SUVmax in its correlation with cardiac functional parameters.

Our results demonstrated that setting the myocardial ^99mTc-PYP uptake threshold at 1.2 × ABPmax was optimal for detecting focal abnormal uptakes. If focal ATTR amyloid deposition in patients with early-stage ATTR-CA can be detected early, new life-prolonging drugs

Limitations

Our small population and single-center study design are weakness of this study. The thresholds and diagnostic accuracy of uptake parameters were based on our small datasets. The present findings require larger, multicenter, prospective validations. Our method needs a manual setting of a polygonal VOI which encompasses the left and right ventricles based on fused SPECT/CT images. However, if we use a proper uptake threshold, the influence of VOI variation is limited. We included only patients

Conclusion

Optimized volumetric evaluation of ^99mTc-PYP SPECT/CT may be superior to the H/CL ratio and SUVmax in diagnosing patients with ATTR-CA and assessing the disease burden. Larger studies are warranted to clarify whether volumetric measurement of bone scintigraphy can identify patients with early-stage ATTR-CA and assess prognosis, disease progression, and treatment response.

New Knowledge Gained

Volumetric evaluation of ^99mTc-PYP SPECT/CT was useful for detecting both focal and diffuse abnormal uptakes and showed a high diagnostic accuracy for ATTR-CA. Cardiac pyrophosphate volume was superior to the H/CL ratio and SUVmax in its correlation with cardiac functional parameters and may be a useful non-invasive marker for assessing the disease burden of ATTR-CA.

Acknowledgments

We thank Mr. Ronald Belisle for his editorial assistance.

Disclosures

SW and KN belong to an endowed department partly funded by Siemens Healthcare and FUJIFILM Toyama Chemical Co., Ltd., the supplier of ^99mTc-PYP in Japan. Others have no relevant disclosures.

Funding

This study was supported by JSPS Grants-in-Aid for Early-Career Scientists in Japan (PI: SW, No. 20K16721).

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Original ArticleVolumetric evaluation of 99mTc-pyrophosphate SPECT/CT for transthyretin cardiac amyloidosis: Methodology and correlation with cardiac functional parameters

Abstract

Background

Methods and Results

Conclusion

Introduction

Section snippets

Study Population

Patient Population

Discussion

Limitations

Conclusion

New Knowledge Gained

Acknowledgments

Disclosures

Funding

J Am Coll Cardiol

J Nuclear Cardiolgy

J Nuclear Cardiol

J Nuclear Cardiol

J Nuclear Cardiol

J Am Coll Cardiol

JACC Cardiovasc Imaging

JACC Cardiovasc Imaging

J Am Coll Cardiol

Original Article
Volumetric evaluation of ^99mTc-pyrophosphate SPECT/CT for transthyretin cardiac amyloidosis: Methodology and correlation with cardiac functional parameters