Quantitative SPECT/CT parameters of myocardial 99mTechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake in suspected cardiac transthyretin amyloidosis

Abstract Background 99mTc-labelled bisphosphonates are used for imaging assessment of patients with transthyretin cardiac amyloidosis (ATTR). Present study evaluates whether quantitative SPECT/CT measurement of absolute myocardial 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) uptake can diagnose patients with suspected ATTR. Methods Twenty-eight patients (25 male, age 80.03 ± 6.99 years) with suspected ATTR referred for Tc-DPD imaging had planar and SPECT/CT imaging of the chest. Three operators independently obtained Tc-DPD myocardial SUVmax and SUVmean above threshold (SMaT) (20, 40 and 60% of SUVmax), using a semi-automated threshold segmentation method. Results were compared to visual grading (0–3) of cardiac uptake. Results Twenty-two patients (78%) had cardiac uptake (2 grade 1, 15 grade 2, 5 grade 3). SUVmax and SMaT segmentation thresholds enabled separating grades 2/3 from 0/1 with excellent inter- and intra-reader correlation. Cut-off values 6.0, 2.5, 3 and 4 for SUVmax, SMaT20,40,60, respectively, separated between grades 2/3 and 0 /1 with PPV and NPV of 100%. SMaT20,40,60(cardiac)/SUVmean (liver) and SMaT20,40,60(cardiac)/SUVmean(liver/lung) separated grades 2 and 3. Conclusion Quantitative SPECT/CT parameters of cardiac Tc-DPD uptake are robust, enabling separation of patients with grades 2 and 3 cardiac uptake from grades 0 and 1. Larger patient cohorts will determine the incremental value of SPECT/CT quantification for ATTR management.

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Assessment of cardiac amyloidosis with 99mTc-pyrophosphate (PYP) quantitative SPECT

EJNMMI Physics ◽

10.1186/s40658-020-00342-7 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Chao Ren ◽

Jingyun Ren ◽

Zhuang Tian ◽

Yanrong Du ◽

Zhixin Hao ◽

...

Keyword(s):

Cardiac Amyloidosis ◽

Activity Concentration ◽

Standardized Uptake Value ◽

Blood Pool ◽

Systematic Difference ◽

Repeated Measurements ◽

Quantitative Spect ◽

Phantom Studies ◽

Grade 3 ◽

Operator Reproducibility

Abstract Background 99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT. Method Thirty-seven consecutive patients who underwent a 99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in the myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). SUVmax was compared among groups of ATTR-CM, AL cardiac amyloidosis, and other pathogens (others) and among categories of Perugini visual scores (grades 0–3). The intra- and inter-operator reproducibility of quantitative SPECT was verified, and the corresponded repeatability coefficient (RPC) was calculated. Results The ICF was 79,327 Bq/ml to convert count rate in pixel to 99mTc activity concentration. PVC factor as a function of the measured activity concentration ratio in the myocardium and blood-pool was [y = 1.424 × (1 − exp(− 0.759 × x)) + 0.104]. SUVmax of ATTR-CM (7.50 ± 2.68) was significantly higher than those of AL (1.96 ± 0.35) and others (2.00 ± 0.74) (all p < 0.05). SUVmax of grade 3 (8.95 ± 1.89) and grade 2 (4.71 ± 0.23) were also significantly higher than those of grade 1 (1.92 ± 0.31) and grade 0 (1.59 ± 0.39) (all p < 0.05). Correlation coefficient (R2) of SUVmax reached 0.966 to 0.978 with only small systematic difference (intra = − 0.14; inter = − 0.23) between two repeated measurements. Intra- and inter-operator RPCs were 0.688 and 0.877. Conclusions 99mTc-PYP quantitative SPECT integrated with adjustable PVC factors is feasible to quantitatively and objectively assess the burden of cardiac amyloidosis for diagnosis of ATTR-CM.

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Assessment of Cardiac Amyloidosis with 99mTc-Pyrophosphate (PYP) Quantitative SPECT

10.21203/rs.3.rs-32649/v2 ◽

2020 ◽

Author(s):

Chao Ren ◽

Jingyun Ren ◽

Zhuang Tian ◽

Yanrong Du ◽

Zhixin Hao ◽

...

Keyword(s):

Cardiac Amyloidosis ◽

Activity Concentration ◽

Standardized Uptake Value ◽

Blood Pool ◽

Systematic Difference ◽

Repeated Measurements ◽

Quantitative Spect ◽

Phantom Studies ◽

Grade 3 ◽

Operator Reproducibility

Abstract Background: 99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT. Method: Thirty-seven consecutive patients underwent a 99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). SUVmax was compared among groups of ATTR-CM, AL cardiac amyloidosis and other pathogens (Others), and among categories of Perugini visual scores (Grade: 0-3). The intra- and inter-operator reproducibility of quantitative SPECT was verified, and the corresponded repeatability coefficient (RPC) was calculated. Results: The ICF was 79,327 Bq/ml to convert count rate in pixel to 99mTc activity concentration. PVC factor as a function of the measured activity concentration ratio in myocardium and blood-pool was [y=1.424*(1-exp(-0.759*x)) +0.104]. SUVmax of ATTR-CM (7.50±2.68) was significantly higher than those of AL (1.96±0.35) and Others (2.00±0.74) (all p<0.05). SUVmax of Grade 3 (8.95±1.89) and Grade 2 (4.71±0.23) were also significantly higher than those of Grade 1 (1.92±0.31) and Grade 0 (1.59±0.39) (all p <0.05). Correlation coefficient (R2) of SUVmax reached 0.966 to 0.978 with only small systematic difference (intra=-0.14; inter=-0.23) between two repeated measurements. Intra- and inter-operator RPCs were 0.688 and 0.877.Conclusions: 99mTc-PYP quantitative SPECT is feasible to quantitatively and objectively assess the burden of cardiac amyloidosis for diagnosis of ATTR-CM.

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Assessment of Cardiac Amyloidosis with 99mTc-Pyrophosphate (PYP) Quantitative SPECT

10.21203/rs.3.rs-32649/v3 ◽

2020 ◽

Author(s):

Chao Ren ◽

Jingyun Ren ◽

Zhuang Tian ◽

Yanrong Du ◽

Zhixin Hao ◽

...

Keyword(s):

Cardiac Amyloidosis ◽

Activity Concentration ◽

Standardized Uptake Value ◽

Blood Pool ◽

Systematic Difference ◽

Repeated Measurements ◽

Quantitative Spect ◽

Phantom Studies ◽

Grade 3 ◽

Operator Reproducibility

Abstract Background: 99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT.Method: Thirty-seven consecutive patients underwent a 99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). SUVmax was compared among groups of ATTR-CM, AL cardiac amyloidosis and other pathogens (Others), and among categories of Perugini visual scores (Grade: 0-3). The intra- and inter-operator reproducibility of quantitative SPECT was verified, and the corresponded repeatability coefficient (RPC) was calculated.Results: The ICF was 79,327 Bq/ml to convert count rate in pixel to 99mTc activity concentration. PVC factor as a function of the measured activity concentration ratio in myocardium and blood-pool was [y=1.424*(1-exp(-0.759*x)) +0.104]. SUVmax of ATTR-CM (7.50±2.68) was significantly higher than those of AL (1.96±0.35) and Others (2.00±0.74) (all p<0.05). SUVmax of Grade 3 (8.95±1.89) and Grade 2 (4.71±0.23) were also significantly higher than those of Grade 1 (1.92±0.31) and Grade 0 (1.59±0.39) (all p <0.05). Correlation coefficient (R2) of SUVmax reached 0.966 to 0.978 with only small systematic difference (intra=-0.14; inter=-0.23) between two repeated measurements. Intra- and inter-operator RPCs were 0.688 and 0.877.Conclusions: 99mTc-PYP quantitative SPECT integrated with adjustable PVC factors is feasible to quantitatively and objectively assess the burden of cardiac amyloidosis for diagnosis of ATTR-CM.

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Assessment of Cardiac Amyloidosis With 99MTC-pyrophosphate (PYP) Quantitative Spect

10.21203/rs.3.rs-32649/v1 ◽

2020 ◽

Author(s):

Chao Ren ◽

Jingyun Ren ◽

Zhuang Tian ◽

Yanrong Du ◽

Zhixin Hao ◽

...

Keyword(s):

Cardiac Amyloidosis ◽

Activity Concentration ◽

Standardized Uptake Value ◽

Blood Pool ◽

Systematic Difference ◽

Repeated Measurements ◽

Quantitative Spect ◽

Phantom Studies ◽

Grade 3 ◽

Operator Reproducibility

Abstract Background: 99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from lightchain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT.Method:Thirty-seven consecutive patients underwent a99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). SUVmaxwas compared among groups of ATTR-CM, ALcardiac amyloidosisand other pathogens (Others), and among categories of Perugini visual scores (Grade: 0-3).The intra- and inter-operator reproducibility of quantitative SPECT was verified, and the corresponded repeatability coefficient (RPC) was calculated. Results: The ICF was 79,327 Bq/mlto convert count rate in pixelto 99mTc activity concentration. PVC factor as a function of the measured activity concentration ratio in myocardium and blood-pool was [y=1.424*(1-exp(-0.759*x))+0.104]. SUVmax of ATTR-CM (7.50±2.68) was significantly higher than those of AL (1.96±0.35) and Others (2.00±0.74) (all p<0.05).SUVmax of Grade 3 (8.95±1.89) and Grade 2 (4.71±0.23) were also significantly higher than those of Grade 1 (1.92±0.31) and Grade 0 (1.59±0.39) (all p <0.05). Correlation coefficient(R2) of SUVmaxreached 0.966 to 0.978 with only small systematic difference (intra=-0.14; inter=-0.23) between two repeated measurements. Intra- and inter-operator RPCs were 0.688and 0.877.Conclusions:99mTc-PYPquantitative SPECT is a reliable method to quantitatively and objectively assess the burden of cardiac amyloidosis for diagnosis of ATTR-CM.

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Cardiac Amyloidosis Therapy: A Systematic Review

Cardiogenetics ◽

10.3390/cardiogenetics11010002 ◽

2021 ◽

Vol 11 (1) ◽

pp. 10-17

Author(s):

Franco Iodice ◽

Marco Di Mauro ◽

Marco Giuseppe Migliaccio ◽

Angela Iannuzzi ◽

Roberta Pacileo ◽

...

Keyword(s):

Heart Failure ◽

Systematic Review ◽

Cardiac Amyloidosis ◽

Restrictive Cardiomyopathy ◽

Novel Therapies ◽

Preserved Ejection Fraction ◽

Cardiac Damage ◽

Transthyretin Amyloidosis ◽

To Come ◽

Almost All

Heart involvement in Cardiac Amyloidosis (CA) results in a worsening of the prognosis in almost all patients with both light-chain (AL) and transthyretin amyloidosis (ATTR). The mainstream CA is a restrictive cardiomyopathy with hypertrophic phenotype at cardiac imaging that clinically leads to heart failure with preserved ejection fraction (HFpEF). An early diagnosis is essential to reduce cardiac damage and to improve the prognosis. Many therapies are available, but most of them have late benefits to cardiac function; for this reason, novel therapies are going to come soon.

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Amyloidosis with Cardiac Involvement: Identification, Characterization, and Management

Current Hematologic Malignancy Reports ◽

10.1007/s11899-021-00626-4 ◽

2021 ◽

Author(s):

Faizi Jamal ◽

Michael Rosenzweig

Keyword(s):

Cardiac Amyloidosis ◽

Systemic Disease ◽

Treatment Options ◽

Diagnostic Algorithm ◽

Transthyretin Amyloidosis ◽

Cardiac Amyloid ◽

Medical Interventions ◽

Light Chain Disease ◽

Organ Response ◽

New Treatment

Abstract Purpose of Review Amyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many times, death. Accurate characterization of the disease based on the nature of the precursor protein, organ involvement, and extent of disease is paramount to guide management. Cardiac amyloidosis is critical to understand because of its impact on prognosis and new treatment options available. Recent Findings New imaging methods have proven to be considerably valuable in the identification of cardiac amyloid infiltration. For treating clinicians, a diagnostic algorithm for patients with suspected amyloidosis with or without cardiomyopathy is shown to help classify disease and to direct appropriate genetic testing and management. For patients with light chain disease, recently introduced treatments adopted from multiple myeloma therapies have significantly extended progression-free and overall survival as well as organ response. In addition, new medical interventions are now available for those with transthyretin amyloidosis. Summary Although cardiac amyloidosis contributes significantly to the morbidity and mortality associated with systemic disease, new tools are available to assist with diagnosis, prognosis, and management.

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Transthyretin Amyloid Cardiomyopathy—Current and Future Therapies

Annals of Pharmacotherapy ◽

10.1177/10600280211000351 ◽

2021 ◽

pp. 106002802110003

Author(s):

Jankhna D. Yadav ◽

Harjot Othee ◽

Kelly A. Chan ◽

Damen C. Man ◽

Paul P. Belliveau ◽

...

Keyword(s):

Cardiac Amyloidosis ◽

Complex Disease ◽

Clinical Presentation ◽

Target Therapy ◽

Data Extraction ◽

Organ Transplant ◽

Standard Of Care ◽

Transthyretin Amyloidosis ◽

Treatment Benefits ◽

Amyloid Cardiomyopathy

Objective: To describe the clinical presentation of transthyretin amyloid cardiomyopathy (ATTR-CM) and discuss current treatments and investigational products and their effect on patient outcomes. Data Sources: A literature search was performed in PubMed (September 2018 to December 2020) using the following keywords: transthyretin amyloidosis, cardiomyopathy, polyneuropathy and transthyretin amyloid cardiomyopathy, monoclonal light-chain, tafamidis, cardiac amyloidosis, ATTR cardiomyopathy, green tea and inhibition of cardiac amyloidosis, AG10, tolcapone, tolcapone and leptomeningeal ATTR, PRX004, NI006, patisiran, inotersen, vutrisiran, AKCEA-TTR-LRx, and NTLA-2001. Study Selection and Data Extraction: Clinical trials were evaluated for evidence supporting pharmacology, safety, efficacy, and measured outcomes. Data Synthesis: Until 2019, there were no approved treatments for ATTR-CM. Treatment consisted of symptom management and organ transplant. Nonpharmacological and pharmacological treatments focused on the symptoms of heart failure (HF) associated with ATTR-CM. However, there are several emerging therapies recently approved or in development to address the underlying pathophysiology. Treatment classes for ATTR-CM include transthyretin stabilizers, human monoclonal antibodies, gene silencers, and CRISPR/Cas9 gene editing. Relevance to Patient Care and Clinical Practice: ATTR-CM is a complex disease in which amyloidosis causes cardiomyopathy. Underdiagnosis is attributed to the clinical presentation being heterogeneous, indistinguishable from HF caused by other etiologies, and the need for invasive testing modalities, including endomyocardial biopsy. Improved diagnostic approaches along with targeted therapies can slow disease progression and enhance patient quality of life. Conclusion: Diagnostic modalities along with biomarker and genetic testing could detect disease earlier and target therapy more accurately. Novel therapies demonstrate potential treatment benefits and can help shape the standard of care for these patients.

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Abstract 16136: Underutilization of Appropriate Testing for Transthyretin Amyloidosis Despite Suspicious Clinical & Echocardiographic Findings

Circulation ◽

10.1161/circ.142.suppl_3.16136 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Katelyn Young ◽

Kinjal Banerjee ◽

Maulin Patel ◽

Sangeeta Prabhakar Bhat ◽

Colin Reynolds ◽

...

Keyword(s):

Genetic Testing ◽

Cardiac Amyloidosis ◽

Chart Review ◽

Diagnostic Testing ◽

Wild Type ◽

Transthyretin Amyloidosis ◽

Highly Sensitive ◽

Amyloid Light Chain ◽

Positive Results ◽

Echocardiographic Findings

Introduction: Both hereditary (hATTR) and wild-type (wtATTR) transthyretin amyloidosis are under-recognized causes of cardiomyopathy (CM) and heart failure. Certain findings on Transthoracic Echocardiography (TTE) and cardiac Magnetic Resonance Imaging (cMRI) are suggestive but not diagnostic of ATTR. Although biopsy historically has been the gold standard for diagnosis, patients can be diagnosed with the highly sensitive and specific technetium-99m pyrophosphate scan (Tc-99m PYP). Genetic testing is recommended to confirm hATTR in patients diagnosed with ATTR cardiac amyloidosis. Despite growing awareness of this condition, many cases remain undiagnosed. This study evaluated if patients with TTEs concerning for infiltrative CM received appropriate diagnostic testing for ATTR-CM. Methods: Our echocardiography registry was queried from January 2011 to March 2020 for patients with our echo lab’s embedded infiltrative CM code. Data on demographics, comorbidities, TTE variables, cMRI results, PYP scans, genetic testing and biopsy results were retrieved from electronic medical records. Thorough manual chart review excluded other causes of CM. Data was expressed as mean ± SD and n (%). Results: We retrieved 510 patients (mean age 64 ± 16 years; 43% female) with TTEs suspicious for infiltrative CM revealing a mean interventricular septal diameter (IVSd) of 1.6 ± 0.3 cm. Only 67 (13%) patients underwent cMRI with 11 (16%) suggestive of cardiac amyloidosis. Of the patients with suspicious TTEs, 16 (3.1%) had PYP scans and 24 (4.7%) had tissue biopsy, with positive results in 7 (44%) and 11 (46%), respectively. Genetic testing in 31 (6%) patients revealed known hATTR mutations in 2 (6.5%) patients. Cardiac amyloidosis was diagnosed in 23 (4.5%) with 11 ATTR (2 hATTR), 5 amyloid light chain, and 7 unknown subtype. Conclusion: Despite clinical and TTE findings suspicious for ATTR-CM, many patients did not undergo appropriate confirmatory testing (see Figure 1).

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Diagnosis of Cardiac Amyloidosis Using Non-Invasive Technics

10.5772/intechopen.97263 ◽

2021 ◽

Author(s):

Eva Strickler ◽

Ernest Tsiaze ◽

Gerrit Hellige ◽

Dominik Zumstein ◽

Dominik Waldmeier ◽

...

Keyword(s):

Cardiac Amyloidosis ◽

Al Amyloidosis ◽

Definite Diagnosis ◽

Diagnostic Features ◽

Transthyretin Amyloidosis ◽

Cardiac Amyloid ◽

Non Invasive ◽

Amyloid Accumulation ◽

Clinically Significant ◽

Multiorgan Disease

Amyloidosis is a rare multiorgan disease defined by a process of irreversible, extracellular accumulation of fibrillar proteins in the tissues, including the heart. Cardiac involvement is seen in most forms of amyloidosis, but it is frequently present and clinically significant in light chain (AL)-amyloidosis as well as transthyretin amyloidosis (ATTR). Cardiac amyloid accumulation leads to a restrictive filling pattern, which must be differentiated from other forms of restrictive and hypertrophic cardiomyopathies due to consequences for the treatment. Evolving knowledge of the disease has led to a definite diagnosis of the cardiac amyloidosis (CA) using non-invasive and low-risk diagnostic features, such as scintigraphy (gamma scan) and cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) and T1 mapping technics. The availability and diagnostic accuracy of these technics has reduced the need for cardiac biopsy. In the following chapter, we will describe common types of CA, the basic concepts, and updates of non-invasive diagnostic features.

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New Oral Anticoagulants vs. Vitamin K Antagonists Among Patients With Cardiac Amyloidosis: Prognostic Impact

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.742428 ◽

2021 ◽

Vol 8 ◽

Author(s):

Eve Cariou ◽

Kevin Sanchis ◽

Khailène Rguez ◽

Virginie Blanchard ◽

Stephanie Cazalbou ◽

...

Keyword(s):

Vitamin K ◽

Cardiac Amyloidosis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Bleeding Complications ◽

Prognostic Impact ◽

Transthyretin Amyloidosis ◽

Increased Risk ◽

All Cause Mortality ◽

History Of

Background: Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA.Methods and Results: 273 patients with CA and history of AA with long term anticoagulation−69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)–were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%; P = 0.013) but no difference for stroke events (4 vs. 2%; P = 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (P < 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality.Conclusion: Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.

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