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Purpose of Review: This review evaluates recent advancements in Technetium-99 m pyrophosphate (99mTc-PYP) imaging for transthyretin amyloid cardiomyopathy (ATTR-CM). We summarize the advantages of single-photon emission computed tomography (SPECT) over planar imaging, the potential impact of quantitative methods, and emerging data for quantifying response to therapy., Recent Findings: The current literature demonstrates the superior diagnostic accuracy of SPECT compared with planar imaging in 99mTc-PYP studies. Emerging quantitative methods, using hybrid SPECT/CT and artificial intelligence, show promise for enhancing diagnostic precision and risk assessment. Recent studies have also highlighted the potential of 99mTc-PYP quantification for monitoring treatment response. 99mTc-PYP SPECT imaging has exceptional diagnostic accuracy for ATTR-CM. Quantitative techniques, which can be facilitated by artificial intelligence, improve risk stratification and may aid in treatment monitoring. Future research should focus on clarifying the clinical role and optimal approach for quantification., Competing Interests: Declarations. Human and Animal Rights and Informed Consent: All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines). Competing Interests: Dr. Miller receives research and consulting support from Pfizer., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The prevalence of wild-type transthyretin (ATTR) amyloidosis is increasing with advancements in diagnostic techniques and growing awareness of the disease worldwide. 99m Tc-labeled pyrophosphate ( 99m Tc-PYP) scintigraphy exhibits high performance in diagnosing ATTR cardiac amyloidosis. This study aimed to validate the characteristics of patients with positive 99m Tc-PYP scintigraphy results in a multicenter setting to provide more accurate case selection criteria., Methods and Results: In total, 180 patients with suspected ATTR amyloidosis underwent 99m Tc-PYP scintigraphy in participating institutions in Japan between January 2018 and July 2022. Of 135 patients included in the analysis, 62 were 99m Tc-PYP-positive. Logistic regression analysis was performed, and the following five factors were adopted to create a scoring system, with each weighted according to its odds ratio value; 1 point was scored for the absence of hypertension, existence of peripheral entrapment neuropathy (carpal tunnel syndrome or spinal canal stenosis), conduction disturbance (the presence of QRS complex ≥120 ms, first-degree atrioventricular block, higher degree of atrioventricular block, or presence of pacemaker implantation), and left ventricular hypertrophy and 2 points for troponin I/T ≥ 0.06 ng/mL. 99m Tc-PYP scintigraphy positivity rate in the 0-point group was 0 %, whereas that in the 6-point group was 100 %. The area under the curve of the criteria was 0.820 (95 % confidence interval, 0.752-0.888; P < 0.001)., Conclusions: The combination of clinical information, which is easily available in local clinics, can provide accurate pretest prediction of positive 99m Tc-PYP scintigraphy results. This will help clinicians to make an early diagnosis of ATTR amyloidosis., Competing Interests: Declaration of competing interest Yuya Matsue received an honorarium from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca, and a collaborative research grant from Pfizer Japan Inc., Otsuka Pharmaceutical Co., EN Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. Hidekazu Tanaka received remuneration from AstraZeneca plc, Ono Pharmaceutical Company, Limited. Pfizer Inc., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Boehringer Ingelheim GmbH, Abbott Japan LLC, and Novartis International AG., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: A 54-year-old woman with a history of end-stage renal disease was found to have infiltrative cardiomyopathy by echocardiography. 99m Tc-pyrophosphate ( 99m Tc-PYP) scintigraphy was positive with a remarkable myocardial uptake. Gene test found a mutation of AGXT , confirming a final diagnosis of primary hyperoxaluria. Radiotracer uptake was due to high myocardial oxalate deposition. This case illustrates false positivity of the 99m Tc-PYP scan caused by hyperoxaluria-associated cardiomyopathy, which raises awareness for other conditions apart from amyloid cardiomyopathy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Wild-type transthyretin amyloid (ATTRwt) deposits in most organs, mainly the heart, ligaments, and tenosynovium. Orthopedic diseases due to ATTRwt deposits often precede overt ATTRwt cardiomyopathy. 99mTc-PYP scintigraphy is highly sensitive in detecting myocardial and extracardiac ATTRwt deposits. However, there are few reports of extracardiac ATTRwt deposits before myocardial deposits confirmed by imaging modalities. We report a case of atrial fibrillation-related heart failure in which 99mTc-PYP scintigraphy showed tracer uptake in extracardiac soft tissues but not in the myocardium, and a biopsy of soft tissues with tracer uptake confirmed ATTRwt deposits. 99mTc-PYP scintigraphy can image extracardiac ATTRwt deposits before myocardial deposits., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cardiac imaging with bone-avid tracers for the diagnosis of transthyretin amyloid (ATTR) cardiac amyloidosis uses only limited quantification, but single-photon emission computed tomography/computed tomography (SPECT/CT) acquisition can provide volumetric assessment with quantification of tracer uptake. Tafamidis is routinely used in the treatment of cardiac amyloidosis, but there are scant data on changes in imaging results during therapy. The purpose of this study was to perform a longitudinal assessment of Tc-99m-pyrophosphate (PYP) imaging to determine if tafamidis therapy results in any change in quantitative measures of tracer uptake., Methods: The study incorporated a prospective, single-center study of ATTR patients being treated with tafamidis using Tc-99m-PYP SPECT/CT to quantify cardiac tracer uptake in the whole heart and left ventricle. Standardized uptake values (SUVs) were adjusted for blood pool activity. Comparison of baseline activity was made to values obtained approximately every 6 months during treatment., Results: Twenty-two patients (77.0±7.5 years old, 86.4% male) were on tafamidis for 15.3±4.0 months, with an average time between baseline and final follow-up study of 16.8±4.7 months. Thirteen patients (59.1%) had multiple follow-up amyloid studies. Statistically significant reductions in total SUVs, SUV volume, and percentage of injected dose were seen. Adjusted for the maximal aortic SUV, the total SUV in the left ventricle decreased by 36.9%, the SUV volume by 38.7%, and the percentage of injected dose decreased by 34.9% (all P values≤0.0001). Over the study duration, there was a decrease of 7.7%/month in the measured metrics., Conclusion: The quantitative SUV measurements from Tc-99m-PYP SPECT/CT revealed an overall decrease in scintographic amyloid burden during the course of tafamidis therapy, but additional work is needed to determine the optimal metrics and improve the reproducibility of the quantification., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: W Lane Duvall reports administrative support was provided by GE Healthcare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

- Diffuse and patchy myocardial uptake of Tc-99m PYP is well established in cases of ATTR-CA. - Chronic myocardial infarction leads to regional myocardial thinning and lack of vascular supply can present as regional sparing 'cold spot' on Tc-99m PYP imaging. - The absence of Tc-99m PYP uptake in vascular regions should raise the possibility of underlying scar., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Abstract: Amyloidosis is a misfolded protein deposition disorder within the extracellular matrix, leading to dysfunction in the affected organ. Primary amyloidosis manifests as AL and ATTR subtypes, wherein AL is associated with plasma cell dyscrasias. Herein we present a case of a patient who underwent investigation due to the presence of bilateral reticulonodular lung infiltrates, suggestive of miliary tuberculosis. 99m Tc-PYP scan revealed widespread radiotracer uptake in the lungs leading to diagnosis of AL amyloidosis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Quantitative technetium-99m-pyrophosphate cardiac single-photon emission computed tomography ( 99m Tc-PYP SPECT/CT) is an emerging method for estimating myocardial burden of transthyretin cardiac amyloidosis (ATTR-CA), but its efficacy in monitoring longitudinal changes remains uncertain. We aimed to investigate longitudinal changes in cardiac ATTR amyloid burden following transthyretin stabilization therapy using visual and quantitative 99m Tc-PYP SPECT/CT and to relate these with changes in cardiac biomarkers and function., Methods: This prospective longitudinal cohort study investigated changes in 99m Tc-PYP SPECT/CT in 23 participants with ATTR-CA on transthyretin stabilization therapy (median: 2.6 years). Quantitative analysis included left ventricular (LV) standardized uptake values (SUVs) (SUV max , SUV mean ), cardiac amyloid activity (CAA; SUV mean ∗LV activity volume), and percent injected dose (%ID) (mean activity concentration∗LV activity volume/injected activity), calculated using a threshold of >1.5 times left atrial blood pool activity concentration on SPECT/CT. Longitudinal changes of paired continuous and ordinal variables were analyzed using Wilcoxon signed-rank test., Results: Following therapy, visual grade decreased significantly (P = 0.003). Several quantitative 99m Tc-PYP metrics also decreased significantly: SUV max (median -0.75, P = 0.011), CAA (median: -406.6, P < 0.001), and %ID (median: -0.45, P < 0.001). Serum transthyretin levels improved (median: +6.5 mg/dL, P = 0.008). Echocardiographic parameters (global longitudinal strain, LV mass index, and LV wall thickness), N-terminal pro-B-type natriuretic peptide, and estimated glomerular filtration rate remained stable., Conclusions: Favorable changes in 99m Tc-PYP myocardial uptake were observed in participants on transthyretin stabilization therapy, whereas echocardiographic parameters and biomarkers remained stable. These results likely signify myocardial ATTR amyloid stabilization rather than amyloid burden regression. Further investigation is needed to understand the implications of these findings., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Abstract: We present a case with systemic amyloidosis secondary to ankylosing spondylitis (AA amyloidosis), whose 99mTc PYP scintigraphy revealed amyloid deposition in the thyroid gland (amyloid goiter). Amyloidosis is characterized by extracellular accumulation of amyloid fibril proteins leading to organ malfunction. Even though AA amyloidosis can be observed in patients with systemic inflammatory diseases, it is a very rare complication in ankylosing spondylitis. SPECT/CT images showed diffuse tracer uptake in enlarged thyroid gland containing fat density areas., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: 99m Tc-3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) scintigraphy and 99m Tc-pyrophosphate (PYP) scintigraphy are highly sensitive modalities for imaging both myocardial and extracardiac amyloid transthyretin in patients with wild-type transthyretin (ATTRwt) amyloidosis. "Loss of bone signal" on planar imaging of 99m Tc-DPD scintigraphy, in which the tracer uptake in bone is obscured by marked tracer uptake in the overlying skeletal muscles, is reported. However, this phenomenon has not yet been documented on 99m Tc-PYP scintigraphy. We describe an 89-year-old woman with ATTRwt amyloidosis in whom "loss of bone signal" together with marked tracer uptake into the skeletal muscles was clearly demonstrated on 99m Tc-PYP scan., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 57-year-old woman who had persistent symptoms of transthyretin cardiac amyloidosis underwent 99m Tc-pyrophosphate ( 99m Tc-PYP) scintigraphy. The 99m Tc-PYP planar and SPECT/CT fusion image showed diffuse myocardial uptake and multiple fractures of the sternum and ribs. These fractures interfered with semiquantitative scores of 99m Tc-PYP uptake, leading to false positive in 99m Tc-PYP imaging., Competing Interests: Conflicts of interest and sources of funding: The current study was supported by the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYGD23016&2021HXFH033), and Quantitative parameters of 99m Tc-PYP SPECT/CT in the Diagnosis of Myocardial Amyloidosis (CGY2023-122)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Transthyretin cardiac amyloidosis (ATTR CA) is increasingly recognized as a cause of heart failure in older patients, with 99m Tc-pyrophosphate imaging frequently used to establish the diagnosis. Visual interpretation of SPECT images is the gold standard for interpretation but is inherently subjective. Manual quantitation of SPECT myocardial 99m Tc-pyrophosphate activity is time-consuming and not performed clinically. We evaluated a deep learning approach for fully automated volumetric quantitation of 99m Tc-pyrophosphate using segmentation of coregistered anatomic structures from CT attenuation maps. Methods: Patients who underwent SPECT/CT 99m Tc-pyrophosphate imaging for suspected ATTR CA were included. Diagnosis of ATTR CA was determined using standard criteria. Cardiac chambers and myocardium were segmented from CT attenuation maps using a foundational deep learning model and then applied to attenuation-corrected SPECT images to quantify radiotracer activity. We evaluated the diagnostic accuracy of target-to-background ratio (TBR), cardiac pyrophosphate activity (CPA), and volume of involvement (VOI) using the area under the receiver operating characteristic curve (AUC). We then evaluated associations with the composite outcome of cardiovascular death or heart failure hospitalization. Results: In total, 299 patients were included (median age, 76 y), with ATTR CA diagnosed in 83 (27.8%) patients. CPA (AUC, 0.989; 95% CI, 0.974-1.00) and VOI (AUC, 0.988; 95% CI, 0.973-1.00) had the highest prediction performance for ATTR CA. The next highest AUC was for TBR (AUC, 0.979; 95% CI, 0.964-0.995). The AUC for CPA was significantly higher than that for heart-to-contralateral ratio (AUC, 0.975; 95% CI, 0.952-0.998; P = 0.046). Twenty-three patients with ATTR CA experienced cardiovascular death or heart failure hospitalization. All methods for establishing TBR, CPA, and VOI were associated with an increased risk of events after adjustment for age, with hazard ratios ranging from 1.41 to 1.84 per SD increase. Conclusion: Deep learning segmentation of coregistered CT attenuation maps is not affected by the pattern of radiotracer uptake and allows for fully automatic quantification of hot-spot SPECT imaging such as 99m Tc-pyrophosphate. This approach can be used to accurately identify patients with ATTR CA and may play a role in risk prediction., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

In patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), the uptake of the tracer on technetium-99m-labeled pyrophosphate ( 99m Tc-PYP) scintigraphy, which indicates amyloid transthyretin (ATTR) per se, is often observed in skeletal muscles, such as the abdominal oblique and gluteal muscles. Among extracardiac biopsies for confirming ATTR deposition in ATTRwt-CA, a 99m Tc-PYP imaging-based computed tomography (CT)-guided core needle biopsy of the internal oblique muscle has relatively high sensitivity. In some patients, the 99m Tc-PYP uptake is more pronounced in the gluteal muscles than in oblique muscles. We herein report two cases of ATTRwt-CA in which a CT-guided biopsy of the gluteus medius muscle with 99m Tc-PYP uptake confirmed the presence of ATTR deposits.

Objective: Cardiac amyloidosis (CA) is a cardiomyopathy characterized by amyloid infiltration in the myocardium. Transthyretin cardiac amyloidosis (TTR-CA), commonly presenting as heart failure with preserved ejection fraction (HFpEF), was the focus of our study, which aimed to identify red flags that heighten suspicion of CA in HFpEF patients., Methods: We prospectively included patients diagnosed with HFpEF. All patients were assessed for TTR-CA red flag features, cardiac and extra-cardiac, as outlined in the 'Diagnosis and Treatment of Cardiac Amyloidosis: A Position Statement of the European Society of Cardiology.' Technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy was performed in 167 HFpEF patients suspected of having TTR-CA. Patients testing positive and negative for TTR-CA were compared based on these red flag features., Results: Out of 167 HFpEF patients, 19 (11.3%) were diagnosed with TTR-CA. In the TTR-CA group, 17 (89.5%) patients were 65 years or older. The presence of three or more red flags differentiated the TTR-CA positive and negative groups (P = 0.040). Features such as low voltage and pseudo infarct patterns were more prevalent in the TTR-CA group (P < 0.001 and P < 0.048, respectively). Left ventricular global longitudinal strain (LV-GLS) was lower in the TTR-CA positive group (P < 0.001). Multivariate analysis identified four variables-older age, pseudo infarct pattern, low/decreased QRS voltage, and LV-GLS-as strong, independent predictors of TTR-CA, with significant odds ratios (ORs) of 7.8, 6.8, 16.9, and 1.2, respectively., Conclusion: In this study, TTR-CA etiology occurs in approximately one in every ten HFpEF patients. The presence of three or more red flags increases the likelihood of TTR-CA. Older age, pseudo infarct pattern, low/decreased QRS voltage, and reduced LV-GLS are the most significant red flags indicating TTR-CA in HFpEF patients.

Introduction: While pyrophosphate uptake imaging with Technetium-99 m pyrophosphate (Tc-99 m PYP) is frequently used for cardiac ATTR amyloid imaging, its role in determining the timing of acute myocardial infarction (AMI) is near forgotten. We present a case that demonstrates the clinical benefit of pyrophosphate uptake imaging in differentiating recent from remote infarction as a reminder of the continued utility of pyrophosphate uptake imaging for this indication., Case and Outcomes: A 68-year-old male was referred for surgical replacement of his bicuspid aortic valve with severe aortic regurgitation. He was clinically well, but an elective pre-operative electrocardiogram suggested an anteroseptal wall infarct of possibly recent onset. Troponin-I was elevated at 430 ng/L (N < 26 ng/L) but did not change significantly over several days. Coronary angiography confirmed an occluded left anterior descending artery. Tc-99 m PYP uptake imaging was then utilised to determine the age of infarct and demonstrated mild regional tracer uptake in the left ventricular apex, consistent with a recent infarction. As the infarct was recent, elective surgery was postponed., Discussion: In this case, the age of the patient's AMI had an important bearing on the timing of his elective surgical aortic valve replacement. Given the recommendation to delay elective cardiac surgery in patients with recent myocardial infarction to reduce peri‑operative morbidity and mortality, this now rare use of pyrophosphate uptake imaging was critical in helping determine when cardiac surgery could be performed safely., Conclusion: This case demonstrates the clinical utility of pyrophosphate uptake imaging in establishing the temporal profile of myocardial infarction to help guide appropriate clinical management., (Copyright © 2024. Published by Elsevier Inc.)

Vicarious excretion of tracer and contrast media is a known phenomenon and is not fully understood [1,2]. We report a case of unexpected vicarious excretion of 99m Tc-pyrophosphate in the gallbladder seen on a scan performed to evaluate suspected cardiac amyloidosis, which is the first report of this phenomenon to the best of our knowledge., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Objective: Most reported research has primarily investigated wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). However, the application of bone scintigraphy for hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has not been systematically investigated. Therefore, in this study, we aimed to evaluate the diagnostic value of 99m Tc-PYP scintigraphy in ATTRv-CA., Methods: Fifty-four patients were enrolled in a highly suspected cardiac amyloidosis cohort. Transthyretin (TTR) gene characteristics were summarized in the ATTRv-CA group. In 99m Tc-PYP scintigraphy, the diagnostic efficiency of the visual score (VGS) and heart-to-contralateral chest (H/CL) ratio were evaluated. Furthermore, the interobserver consistency among the diagnosticians was investigated., Results: Twenty-eight patients were diagnosed with ATTRv-CA with eight genotypes. The Ala97Ser genotype accounts for 46% (n = 13) with a mean age of disease onset, definite diagnosis, and interval of 61.6 ± 1.9, 66.5 ± 1.3, and 4.0 (3.0, 6.2) years, respectively. Their VGS is Grade 3, and their H/CL ratio is higher than that of the non-Ala97Ser group, but no statistical significance exists (mean H/CL: 1.95 ± 0.06 vs. 1.87 ± 0.02, p = 0.844). Additionally, ATTRv-CA patients showed VGS ≥ 2, and mean H/CL ratio of 2.09 ± 0.06. The sensitivity and specificity of VGS were 100% and 65%, respectively. And the interobserver consistency analysis of VGS showed the intraclass correlation coefficient is 0.522. The best cutoff value of H/CL ratio was 1.51 (AUC = 0.996), and the diagnostic consistency of H/CL (bias: 0.018) was high., Conclusions: Ala97Ser is the most common genotype in ATTRv-CA in our cohort, with characteristics of later onset and rapid progression, but delayed diagnosis and extensive 99m Tc-PYP uptake. Overall, ATTRv-CA patients showed moderate-to-extensive myocardial 99m Tc-PYP uptake. Additionally, VGS carries subjectivity, low specialty and interobserver consistency. But H/CL exhibit high diagnostic efficacy and interobserver consistency. The H/CL ratio is more useful than VGS., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background: Technetium-99m-pyrophosphate ( 99m Tc-PYP) uptake in the internal oblique muscle (IOM), which is often observed in patients with wild-type transthyretin cardiac amyloidosis (ATTR-CA), indicates amyloid transthyretin (ATTR) deposition., Objective: This study aimed to assess the safety and efficacy of 99m Tc-PYP imaging-based computed tomography (CT)-guided core-needle biopsy of the IOM as a new extracardiac screening biopsy for confirming the presence of ATTR deposits., Methods: Patients with suspected ATTR-CA in whom myocardial tracer uptake was detected on chest- and abdomen-centered images of 99m Tc-PYP scintigraphy underwent CT-guided core-needle biopsy at the site with the highest tracer uptake in the IOM between September 2021 and November 2022., Results: All 18 consecutive patients (mean age, 86.3 years ± 6.5; 61.1% male) enrolled in the study showed 99m Tc-PYP uptake into the IOM. Adequate tissue samples were obtained from all patients except one without serious complications. Immunohistochemical analysis confirmed ATTR deposits in 16/18 (88.9%) patients. In the remaining two patients, ATTR deposits were observed via endomyocardial biopsy. All patients were diagnosed with wild-type ATTR-CA based on transthyretin gene sequence testing results., Conclusion: In wild-type ATTR-CA, 99m Tc-PYP imaging-based CT-guided core-needle biopsy of the IOM could be used as an extracardiac screening biopsy to confirm the presence of ATTR deposits.

Background: We employed deep learning to automatically detect myocardial bone-seeking uptake as a marker of transthyretin cardiac amyloid cardiomyopathy (ATTR-CM) in patients undergoing 99mTc-pyrophosphate (PYP) or hydroxydiphosphonate (HDP) single-photon emission computed tomography (SPECT)/computed tomography (CT)., Methods: We identified a primary cohort of 77 subjects at Brigham and Women's Hospital and a validation cohort of 93 consecutive patients imaged at the University of Pennsylvania who underwent SPECT/CT with PYP and HDP, respectively, for evaluation of ATTR-CM. Global heart regions of interest (ROIs) were traced on CT axial slices from the apex of the ventricle to the carina. Myocardial images were visually scored as grade 0 (no uptake), 1 (uptakeribs). A 2D U-net architecture was used to develop whole-heart segmentations for CT scans. Uptake was determined by calculating a heart-to-blood pool (HBP) ratio between the maximal counts value of the total heart region and the maximal counts value of the most superior ROI., Results: Deep learning and ground truth segmentations were comparable (p=0.63). A total of 42 (55%) patients had abnormal myocardial uptake on visual assessment. Automated quantification of the mean HBP ratio in the primary cohort was 3.1±1.4 versus 1.4±0.2 (p<0.01) for patients with positive and negative cardiac uptake, respectively. The model had 100% accuracy in the primary cohort and 98% in the validation cohort., Conclusion: We have developed a highly accurate diagnostic tool for automatically segmenting and identifying myocardial uptake suggestive of ATTR-CM., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

Rationale and Objectives: This study aimed to assess the utility of cardiac magnetic resonance imaging (MRI) T1 and T2 mapping as quantitative imaging biomarkers in transthyretin amyloid cardiomyopathy (ATTR-CM)., Materials and Methods: This study retrospectively evaluated 74 patients with confirmed wild-type ATTR-CM who underwent cardiac MRI, 99m Tc-labeled pyrophosphate ( 99m Tc-PYP) scintigraphy, and echocardiography. We assessed the quantitative disease parameters, for example, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS) by echocardiography, native T1, extracellular volume fraction (ECV), and native T2 value by cardiac MRI, heart-to-contralateral ratio (H/CL) by 99m Tc-PYP, and high-sensitive cardiac troponin T. Myocardial native T2 of ≥50 ms was defined as myocardial edema. Correlations between the disease's quantitative parameters were evaluated, and the ECV was compared to other parameters in ATTR-CM with/without myocardial edema., Results: ECV in all patients with ATTR-CM revealed a strong correlation with native T1 (r = 0.62), a moderate correlation with hs-TnT (r = 0.59), LVEF (r = -0.48), GLS (r = 0.58), and H/CL (r = 0.48). Correlations between ECV and other quantitative parameters decreased in ATTR-CM with myocardial edema except for H/CL. Meanwhile, the correlations increased in ATTR-CM without myocardial edema., Conclusion: The presence of myocardial edema affected the interpretation of ECV assessment, although ECV can be a comprehensive imaging biomarker for ATTR-CM. ECV showed a significant correlation with various quantitative disease parameters and can be a reliable disease monitoring marker in patients with ATTR-CM when myocardial edema was excluded., Competing Interests: Declaration of Competing Interest The authors have no direct or indirect financial interest in the products used or the subject matter discussed in this manuscript., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to monitor the effectiveness of hATTR-CM treatment. The objective of this study was to examine how eplontersen therapy influences the semiquantitative uptake of technetium-99m-pyrophosphate in individuals diagnosed with hATTR-CM., Methods and Results: We retrospectively analyzed a prospective cohort from the NEURO-TTRansform trial, including patients with hATTR-CM receiving eplontersen (45 mg/4 weeks). A control group comprised patients with hATTR-CM who had not received eplontersen, inotersen, tafamidis, or patisiran. Technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography was conducted at baseline and during follow-up. Thirteen patients with hATTR-CM were enrolled, with 6 receiving eplontersen and 7 serving as the control group. The median follow-up time was 544 days. The eplontersen group exhibited a significant decrease in volumetric heart and lung ratio (3.774 to 2.979, P =0.028), whereas the control group showed no significant change (4.079 to 3.915, P =0.237). Patients receiving eplontersen demonstrated a significantly greater reduction in volumetric heart and lung ratio compared with the control group (-20.7% versus -3.4%, P =0.007)., Conclusions: The volumetric heart and lung ratio used to quantify technetium-99m-pyrophosphate uptake showed a significant reduction subsequent to eplontersen treatment in individuals diagnosed with hATTR-CM. These findings suggest the potential efficacy of eplontersen in treating hATTR-CM and highlight the value of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography as a tool for monitoring therapeutic effectiveness.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM), characterized by the extracellular deposition of an insoluble amyloid protein in the heart, is one of the main causes of heart failure in elderly patients. In this study, our primary objective was to explore the diverse applications and temporal significance of 1-h and 3-h imaging using 99m Tc-PYP in the context of ATTR-CM. Additionally, we compared tracer kinetics in the heart and bone to comprehensively assess the diagnostic advantages and time-related considerations associated with these two incubation periods., Methods: Twenty-seven patients at Nagasaki University Hospital who underwent 99m Tc-PYP planar, and SPECT cardiac imaging were classified into two groups (ATTR-CM-positive and -negative groups) based on the American Heart Association statement. Cardiac retention was assessed with both a semiquantitative visual score and a quantitative analysis. To assess bone accumulation, a ROI with an equal volume was drawn on the sternum and calculated as the bone-to-contralateral ratio (B/CL). We also evaluated correlation between heart-to-contralateral lung (H/CL) ratio and left ventricular wall thickness., Results: Among patients who underwent 99m Tc-PYP imaging, the H/CL ratio was significantly higher at 1 h than at 3 h regardless of the group (from 2.20 ± 0.36 to 1.99 ± 0.35, p < 0.01 in the positive group and from 1.35 ± 0.12 to 1.19 ± 0.21, p = 0.01 in the negative group). The gap of H/CL between highest H/CL of negative case and lowest H/CL of positive case was narrower in 3 h. On the other hand, correlation between H/CL and left ventricular posterior wall thickness tends to be clearer in 3 h (p = 0.12, r = 0.30 for 1 h, p = 0.04, r = 0.39 at 3 h)., Conclusion: Our study suggests that both 1-h and 3-h incubation times for 99m Tc-PYP imaging have different benefits for ATTR cardiac amyloidosis. A one-hour incubation may be preferable for differential diagnostic purposes, while a three-hour incubation may provide greater utility in evaluating disease severity., (© 2024. The Author(s).)

Competing Interests: Disclosures None.

Background: SPECT improves diagnostic specificity of Technetium-99m pyrophosphate (PYP) scintigraphy. Diagnostic performance of PYP data, reconstructed as either chest or cardio-focal SPECT is not known., Methods: In this quality assurance study, blinded evaluation of PYP SPECT/CT data from 102 Caucasian patients (mean age 76 ± 11 years, 67% men) was performed by two readers. Reader 1 reviewed planar and PYP chest SPECT, while reader 2 reviewed planar and cardio-focal PYP SPECT. Demographic, clinical, and other testing data were obtained from the electronic medical records., Results: A total of 41 patients (40%) were considered positive based on myocardial uptake on chest PYP SPECT. Of these, 98% of the patients had a Perugini score ≥ 2 on planar imaging. There was good agreement between the two readers for visual score ≥ 2 (k = .88, P < .001) and excellent agreement for myocardial uptake on tomographic imaging (98%, P < .001). Only one study was categorized as false negative by cardio-focal SPECT reconstruction. Non-diffuse myocardial uptake was identified in 22% of those with a positive PYP SPECT., Conclusion: When read by experienced readers, chest and cardio-focal reconstruction of PYP SPECT have comparable diagnostic performance. A substantial proportion of patients with a positive PYP SPECT have a non-diffuse distribution of PYP. Given the possibility of misclassification of non-diffuse myocardial uptake on cardio-focal reconstruction alone, chest reconstruction of PYP scintigraphy should be strongly considered., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Myocardial imaging with bone agents such as Tc-99 m PYP and HMDP has assumed a central role in the evaluation of patients with suspected transthyretin (TTR) amyloidosis. Visual scoring (VS) (0-3 +) and the heart to contralateral lung ratio (HCL) classify many patients as equivocal when mediastinal uptake is apparent but cannot be further differentiated into myocardial uptake versus blood pool. SPECT imaging has been recommended but current reconstruction protocols frequently produce amorphous mediastinal activity that also fails to discriminate between myocardial activity and blood pool. We hypothesized that interactive filtering interactively using a deconvolving filter would improve this., Methods: We identified 176 sequential patients referred for TTR amyloid imaging. All patients had planar imaging, 101 had planar imaging with a large field of view camera that allowed HCL measurements. SPECT imaging was performed on a 3-headed digital camera with lead fluorescence attenuation correction. One study was excluded for technical reasons. We created software to allow interactive filtering while reconstructing the images then overlay them on attenuation mu maps to assist localization of myocardial/mediastinal uptake. Conventional Butterworth and an interactive inverse Gaussian filters were employed to differentiate myocardial uptake from residual blood pool. We defined "clean blood pool" (CBP) as recognizable blood pool with no activity in the surrounding myocardium. A scan was determined diagnostic if it showed CBP, positive uptake or no identifiable mediastinal uptake., Results: 76/175 (43%) were equivocal (1 +) by visual uptake. Of these 22 (29%) were diagnostic by Butterworth but 71 (93%) were by inverse gaussian (p < .0001). 71/101 (70%) were equivocal by HCL (1-1.5). Of these, 25 (35%) were diagnostic by Butterworth but 68 (96%) were diagnostic by inverse gaussian (p < .0001). This was driven by a greater than threefold increase in the identification of CBP by inverse gaussian filtering., Conclusion: CBP can be identified in the vast majority of patients with equivocal PYP scans using optimized reconstruction and can greatly reduce the number of equivocal scans., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Introduction: Technetium-labeled bone-avid radiotracers can be used to diagnose transthyretin cardiac amyloidosis (ATTR-CA). Extracardiac uptake of technetium pyrophosphate (Tc-99m PYP) in this context has not been extensively explored and its significance is not well characterized. We assessed extracardiac Tc-99m PYP uptake in individuals undergoing nuclear scintigraphy and the extent of clinically actionable findings., Methods: The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study utilizes Tc-99m PYP imaging to identify ATTR-CA in self-identified Black and Caribbean Hispanic participants ≥ 60 years old with heart failure. We characterized the distribution of extracardiac uptake, including stratification of findings by timing of scan (1 hour vs 3 hours after Tc-99m PYP administration) and noted any additional testing in these subjects., Results: Of 379 participants, 195 (51%) were male, 306 (81%) Black race, and 120 (32%) Hispanic ethnicity; mean age was 73 years. Extracardiac Tc-99m PYP uptake was found in 42 subjects (11.1%): 21 with renal uptake only, 14 with bone uptake only, 4 with both renal and bone uptake, 2 with breast uptake, and 1 with thyroid uptake. Extracardiac uptake was more common in subjects with Tc-99m PYP scans at 1 hour (23.8%) than at 3 hours (6.2%). Overall, four individuals (1.1%) had clinically actionable findings., Conclusion: Extracardiac Tc-99m PYP uptake manifested in about 1 in 9 SCAN-MP subjects but was clinically actionable in only 1.1% of cases., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Various parameters derived from technetium-99m pyrophosphate ( 99m Tc-PYP) single-photon emission computed tomography (SPECT) correlate with the severity of transthyretin amyloid cardiomyopathy (ATTR-CM). However, the optimal metrics and image acquisition timing required to quantify the disease burden remain uncertain., Methods and Results: We retrospectively evaluated 99m Tc-PYP SPECT/CT images of 23 patients diagnosed with ATTR-CM using endomyocardial biopsies and/or gene tests. All patients were assessed by SPECT/CT 1 hour after 99m Tc-PYP injection, and 13 of them were also assessed at 3 hours. We quantified 99m Tc-PYP uptake using the volumetric parameters, cardiac PYP volume (CPV) and cardiac PYP activity (CPA). We also calculated the SUVmax ratios of myocardial SUVmax/blood pool SUVmax, myocardial SUVmax/bone SUVmax, and the SUVmax retention index. We assessed the correlations between uptake parameters and the four functional parameters associated with prognosis, namely left ventricular ejection fraction, global longitudinal strain, myocardial extracellular volume, and troponin T. CPV and CPA correlated more closely than the SUVmax ratios with the four prognostic factors. Significant correlations between volumetric parameters and prognostic factors were equivalent between 1 and 3 hours., Conclusions: The disease burden of ATTR-CM was quantified more accurately by volumetric evaluation of 99m Tc-PYP SPECT/CT than SUVmax ratios and the performance was equivalent between 1 and 3 hours., (© 2023. The Author(s).)

Abstract: With documented high specificity, 99m Tc-pyrophosphate (PYP) scan enables the diagnosis of transthyretin cardiomyopathy to be made reliably without endomyocardial biopsy in patients who do not have monoclonal gammopathy. We report a case with extensive myocardial uptake of Perugini 3 score in the 3-hour 99m Tc-PYP myocardial SPECT that suggested transthyretin cardiac amyloidosis. However, a followed endomyocardial biopsy revealed no amyloid deposition. In this case, hyperphosphatemia was the most likely and presumptive cause of the false-positive 99m Tc-PYP scan. With this case, our experiences of the potential causes of false-positive results of 99m Tc-PYP are further expanded., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Technetium-99mm pyrophosphate (Tc-PYP) scintigraphy is a highly accurate non-invasive method for the diagnosis of transthyretin (ATTR) cardiac amyloidosis. Prognosis for this disease is improved following treatment with the transthyretin (TTR) stabilizer tafamidis. Although tafamidis slows disease progression, its effects on myocardial amyloid and Tc-PYP uptake remain unclear. We present a patient with ATTR cardiac amyloidosis who had a strongly positive initial Tc-PYP scan, with a dramatic decrease in Tc-PYP uptake on repeat scan after 3 years of tafamidis treatment. However, myocardial biopsy showed persistent diffuse amyloid deposits. This case highlights the need for further studies regarding the utility of serial Tc-PYP scans in monitoring the progress of ATTR cardiomyopathy., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)