99mTc-pyrophosphate Scintigraphy Research Articles

Simplified dual-time-point 99mTc-pyrophosphate scintigraphy in patients with suspected transthyretin amyloid cardiomyopathy: A single center series

Simplified dual-time-point 99mTc-pyrophosphate scintigraphy in patients with suspected transthyretin amyloid cardiomyopathy: A single center series

Cost-effectiveness of systematic screening and treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in patients with heart failure with preserved ejection fraction (HFpEF) in United States

BackgroundTransthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure in clinical practice. 99mTc-pyrophosphate scintigraphy (PYP-scan) improves the accuracy of ATTR-CM detection, enabling timely initiation of tafamidis, a drug that slows the progression of ATTR-CM and lowers the risk of adverse cardiac events. PYP-scans, serum free light-chain (FLC) test and immunofixation electrophoresis (IFE) are critical components of a systematic screening. We assessed the cost-effectiveness of universal systematic screening (USS) compared to standard-of-care (SoC) selected clinical referrals for the systematic screening in patients aged 60 years or older with heart failure with preserved ejection fraction (HFpEF) and ventricular wall thickness of at least 12 mm. MethodsTwo screening strategies, USS versus SoC screening for ATTR-CM were compared in a model-based assessment. Treatment decisions were based upon the accuracy of each screening strategy, which was followed by Markov state transitions across New York Heart Association (NYHA) functional classes and death. Model inputs were identified from a literature review. We calculated lifetime cost in 2022 US dollars and quality adjusted life-years (QALYs) of each strategy. The primary outcome was the incremental cost-effectiveness ratio (ICER). ResultsThe USS was associated with a significant increase in lifetime costs ($124,380 vs. $70,412) and modest improvement in QALYs (4.42 QALYs vs 4.36 QALYs). The ICER for the USS was $919,509 per QALY gained. ICER was sensitive to the age at the time of ATTR-CM diagnosis, true prevalence rate of ATTR-CM, and daily cost of tafamidis. ConclusionsOwing to the high cost of treatment with tafamidis, USS along with PYP scan for ATTR-CM in older HFpEF patients with ventricular wall thickening is unlikely to become a cost-effective strategy at a liberal WTP threshold.

Predictive Value of high-sensitivity cardiac troponin T in patients undergoing 99mTc pyrophosphate scintigraphy for suspected transthyretin amyloid cardiomyopathy

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (1,2). 99mTc- pyrophosphate cardiac scintigraphy (PYP) enables accurate, noninvasive diagnosis of ATTR-CM when coupled with appropriate clinical and laboratory evaluations to rule out light chain amyloidosis (3,4). High sensitivity cardiac troponin T (hs-cTnT) is routinely assessed for diagnostic purposes when ATTR-CM is suspected in clinical practice. Purpose To investigate the diagnostic performance of hs-cTnT in patients undergoing PYP for suspected ATTR-CM. Methods Observational study of patients undergoing PYP at a United States (US) cardiac amyloidosis referral center from 2013 to September 2022 and with at least one hs-cTnT value available within 1 year. 3-hour planar imaging followed by single photon-emission computed tomography with computed tomography was performed. Final diagnoses of ATTR-CM were validated using all clinical information. The lowest reportable clinical value for hs-cTnT in the US is <6 ng/L (limit of quantitation). Results A total of 1572 patients underwent PYP and had a hs-cTnT value available within the study period. Of these, ATTR-CM was diagnosed in 475 patients (30%). Median (IQR) hs-cTnT was 48 (31-67) ng/L in patients with ATTR-CM and 26 (13-48) ng/L in those without. The area under the curve of hs-cTnT for the diagnosis of ATTR-CM was 0.69 (0.67-0.72). Among patients with a very low hs-cTnT value, i.e. <6 ng/L (n=100, 6.4% of the overall cohort), 7 (7%) patients had a final ATTR-CM diagnosis while 93 (93%) did not. Therefore, a threshold of <6 ng/L demonstrated a negative predictive value (NPV) of 93% (IQR 88, 98) and a sensitivity of 99% (97, 100) for ruling out ATTR-CM. The highest NPV was achieved with a threshold of 12 ng/L; 269 (17%) patients had hs-cTnT below this value and, of those, only 16 (6%) had a final diagnosis of ATTR-CM. This resulted in a NPV of 94% (91, 97) and a sensitivity of 97% (95, 98) for ruling out ATTR-CM. When considering progressively increasing hs-cTnT values as potential thresholds to aid in the prediction of ATTR-CM (Figure), we observed a progressive increase in specificity (above 90% for hs-cTnT values > 95 ng/L), but the positive predictive value (PPV) remained low (below 50%). Conclusions Among patients undergoing PYP for suspected ATTR-CM at a US referral center, a very low hs-cTnT value was present in a minority of patients but demonstrated good performance in ruling out ATTR-CM. The highest NPV (94%) was achieved with a threshold of < 12 ng/L. Higher hs-cTnT values showed a good specificity, but PPV remained low. Therefore, while a very low hs-cTnT might be of help in identifying those at low risk of ATTR-CM, the ubiquitous presence of increased hs-cTnT in many of these patients suggests the need for a multiparametric diagnostic approach to make the diagnosis.hs-cTnT in patients undergoing PYP scan

In the thick of it: hereditary cardiac amyloidosis identified by 124I-AT-01 PET imaging but not cardiac MRI or SPECT 99mTc pyrophosphate scintigraphy

In the thick of it: hereditary cardiac amyloidosis identified by 124I-AT-01 PET imaging but not cardiac MRI or SPECT 99mTc pyrophosphate scintigraphy

Clinical Application of 99mTc-Pyrophosphate Scintigraphy for Diagnosis of Cardiac Amyloidosis: A Case Series.

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy resulting from deposition of insoluble amyloid protein in the myocardial interstitium. The accumulation of amyloid protein causes the myocardium to thicken and stiffen, leading to diastolic dysfunction and, eventually, heart failure. Two primary types of amyloidosis-transthyretin and immunoglobulin light chain-account for nearly 95% of all CA diagnoses. Three case studies are presented. The first demonstrates a patient positive for transthyretin amyloidosis, the second demonstrates a patient positive for light-chain CA, and the third demonstrates a patient showing blood-pool uptake on the [99mTc]Tc-pyrophosphate scan but negative for CA.

New quantitative indices of cardiac amyloidosis with 99mTc-pyrophosphate scintigraphy.

Amyloid light chain (AL) and transthyretin (ATTR) are the major subtypes of cardiac amyloidosis (CA). 99mTc-pyrophosphate (PYP) scintigraphy is used to differentiate ATTR from other CA subtypes. We adapted the standardized uptake value (SUV) for 99mTc-PYP and proposed two quantitative indices, amyloid deposition volume (AmyDV) and total amyloid uptake (TAU). This study aimed to evaluate the utility of these quantitative indices in differentiating ATTR from non-ATTRs. Before the SUV measurement, the Becquerel calibration factor (BCF) of 99mTc was obtained by a phantom experiment. Thirty-two patients who had undergone hybrid SPECT/CT imaging 3h after injection of 99mTc-PYP (370MBq) were studied. CT attenuation correction for image reconstruction was applied in all. We calculated SUV, AmyDV, and TAU using a quantitative analysis software program for bone SPECT (GI-BONE) and analyzed AmyDV using two methods: threshold method (set 40%); and constant value method (average SUVmax of ribs). We assessed the diagnostic ability of heart-to-contralateral lung (H/CL) ratio, SUV, AmyDV, and TAU to differentiate ATTR from non-ATTR using receiver operating characteristic (ROC) analysis. Statistically significant differences in all quantitative indices were observed between ATTR and non-ATTR. The area under the curve of each quantitative index for discriminating between ATTR and non-ATTR were as follows: H/CL, 0.997; SUVmax, 0.953; SUVmean (M1), 0.964; SUVmean (M2), 0.969; AmyDV (M1), 0.875; AmyDV (M2), 0.974; and TAU, 0.974. The AmyDV (M2) had higher diagnostic ability than AmyDV (M1). Thus, TAU was calculated as AmyDV (M2) × SUVmean (M2). In the ROC curve, SUV, AmyDV, and TAU had almost the same diagnostic ability as H/CL in distinguishing ATTR from non-ATTRs. We propose two novel 3D-based quantitative parameters (AmyDV and TAU) that have almost equal ability to discriminate ATTR from non-ATTR.

Comparison of 1-h with 3-h planar 99mTc-pyrophosphate scintigraphy in patients with suspected transthyretin cardiac amyloidosis using SPECT as a reference standard.

The purpose of this study was to examine the diagnostic value of planar 99mTc-pyrophosphate (PYP) imaging at 1 and 3h after tracer administration in patients with suspected transthyretin cardiac amyloidosis (ATTR-CA) using SPECT as a reference standard. We also tested whether blood pool activity of PYP is associated with renal dysfunction. PYP images of 109 consecutive patients with suspected ATTR-CA were retrospectively reviewed. The myocardial PYP uptake was visually graded on a scale of 0 to 3 and quantified with the heart-to-contralateral (H/CL) ratio in accordance with the current expert consensus recommendations. The diagnostic value of planar images for identifying positive PYP SPECT was assessed by a receiver-operating characteristic curve analysis with the area under the curve (AUC). The uptake ratios of the ascending and descending aorta, left atrium, and trapezius muscle divided by the liver uptake were measured on SPECT images and compared to the renal function. A total of 41 patients (38%) had myocardial PYP uptake on SPECT images. In comparison with the visual scores on 1-h anterior planar images, those on 3-h anterior planar images had lower sensitivity (80.5% vs. 97.6%) and higher specificity (86.8% vs. 55.9%) for identifying positive PYP SPECT. The ROC analysis showed that the combination of visual scores on both 1-h and 3-h anterior planar images had significantly higher AUC values in comparison with 1-h anterior planar images alone (0.90 [95% CI 0.83-0.94] vs. 0.83 [95% CI 0.75-0.88]; P < 0.001), which was comparable to the AUC values on 3-h anterior planar images alone (0.88 [95% CI 0.80-0.92]; P = 0.071). In comparison with visual scores on 1-h or 3-h anterior planar images alone, the combination of visual scores and H/CL ratio did not significantly improve the diagnostic value for identifying positive PYP SPECT (P = 0.73 and P = 0.50, respectively). The uptake ratios of ascending aorta/liver, descending aorta/liver, left atrium/liver, and trapezius muscle/liver were not significantly associated with the serum creatinine level or estimated glomerular filtration rate (P > 0.05 for all). In the assessment of ATTR-CA using PYP imaging, visual scores on 3-h anterior planar images for identifying positive PYP SPECT had lower sensitivity and higher specificity in comparison with those on 1-h anterior planar images. The diagnostic value of the visual scores on 1-h and 3-h anterior planar images was not improved by adding the H/CL ratio. Blood pool activity of PYP was not significantly associated with renal dysfunction.

Abstract 14221: External Validation of Transthyretin Cardiac Amyloid Score Supports Use as Low-Cost Screening Tool

Introduction: Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure. Novel therapies for transthyretin (TTR) CA elevate the need for early identification when treatment has the greatest efficacy. The TTR CA score (TCAS) was recently developed to predict the likelihood of TTR CA in patients undergoing 99mTc-pyrophosphate scintigraphy (PYP) scanning. Its simple inputs could be easily extracted from the electronic health record (EHR), suggesting possible use as a quick, EHR-based screening tool. We perform the first external validation of the TCAS using only EHR-extracted data. We hypothesized that a screening algorithm like TCAS could be generalizable and feasible to implement using our EHR. Methods: EHR data were extracted on all patients at a large academic medical center who underwent PYP scans between 2017 and 2022. PYP scan was considered positive if the patient was part of our institution’s registry of patients with confirmed CA. Inputs - age, sex, echocardiogram wall thickness and ejection fraction, and hypertension diagnosis codes - were converted to TCAS scores. Area under the receiver operating characteristic curve (AUROC) was calculated to analyze predictive performance. Using a TCAS ≥6 as the threshold for high-risk, performance characteristics were calculated. Results: Of 365 patients who underwent PYP scan, 335 had sufficient records to calculate a TCAS. Of these 335 patients, 69 (20.6%) had positive PYP scans. Median TCAS was 5 (interquartile range 4,7). The AUROC was 0.826, with a sensitivity of 87.0%, specificity of 63.9%, positive predictive value of 38.5%, and negative predictive value (NPV) of 95.0%. Conclusions: External validation of the TCAS supports its strong predictive performance with comparable AUROCs to the initial study (0.84-0.89). Clinically, with its high NPV, the TCAS has potential to serve as a simple, low-cost screen to avoid costly PYP scans. We demonstrate the ability to extract all inputs from the EHR, without need for manual chart review or calculation, suggesting that the TCAS could function as an EHR-based screening tool. Low-cost screening tools are needed to identify patients who would benefit from TTR CA workup with PYP scanning, facilitating treatment at earlier disease stages.

Illustrative review of cardiac amyloidosis by multimodality imaging.

Cardiac involvement in amyloidosis is characterized by the extracellular deposition of misfolded proteins in the heart with the pathognomonic histological property of green birefringence when viewed under cross-polarized light after staining with Congo red. Although considered a rare disease, recent data suggest that cardiac amyloidosis is underappreciated as a cause of common cardiac diseases or syndromes. The prognosis for transthyretin (TTR) amyloidosis (ATTR) amyloidosis is better than that for amyloid light-chain amyloidosis; however, it is not as good as for other etiologies heart failure. Although there is no proven therapy for patients with ATTR cardiomyopathy (ATTR-CM), tafamidis meglumine, a TTR stabilizer, a study in 2018 found it was associated with reductions in all-cause mortality and cardiovascular-related hospitalizations, as well as with a reduction in the decline in functional capacity and quality of life compared with a placebo for patients with ATTR-CM. As a result of these findings, tafamidis meglumine is currently the only drug approved for patients with both wild-type and variant ATTR-CM, and should be considered for patients whose survival can be reasonably expected. In addition, recent advances in cardiac imaging, diagnostic strategies, and therapies have improved so that interest has been growing in the diagnosis of ATTR-CM by means of non-invasive imaging modalities as a potential means for better management of patients with ATTR-CM. This article reviews the efficacy of non-invasive imaging, especially echocardiography, cardiac magnetic imaging, and 99mTc-pyrophosphate scintigraphy for diagnosis of cardiac amyloidosis.

Transthyretin cardiac amyloidosis scintigraphy, experience in a reference cardiology center

Funding AcknowledgementsType of funding sources: Public hospital(s). Main funding source(s): Instituto Nacional de Cardiologia Ignacio ChavezIntroductionTransthyretin cardiac amyloidosis (ATTR-CA) is a progressive disease that significantly reduces patients" quality of life and survival.1 In our country there are no statistics of this disease, only isolated cases. The ability to diagnose it has dramatically improved since the 2019 Multisociety Consensus for Multimodality Imaging.2,3 The study aimed to know patients" demographic and imaging characteristics in suspected ATTR-CA and the prevalence of positive cases in a reference Cardiology Center using 99mTc-pyrophosphate scintigraphy (99mTc-PYP).MethodsProspective, observational study approved by Institutional committees. We studied with 99mTc-PYP patients from November 2019 to December 2020 sent to the Nuclear Cardiology Department with clinical suspicion of ATTR-CA and negative light chain quantification. We included parameters as red flags, ECHO suggestive findings (septal thickness >12 mm, diastolic dysfunction), and MRI suggestive findings. ATTR-CA was diagnosed by clinical suspicious, positive scintigraphy, and negative serum studies. 99mTc-PYP were acquired according to current recommendations. Frequency distribution of categorical variables were reported as frequencies and percentages; continuous variables are presented in mean. Mann-Whitney U tests were conducted for continuous variables, while Fisher"s exact test was performed for categorical variables.ResultsDue to the Covid-19 pandemic, our Cardiology Hospital reconverted to covid attention; we studied a reduced number, and they were mainly inpatients: total 35 (28-inpatients, 7-outpatients). 21 (60%) were male, 14 (40%) were female, average age was 56.5 yo. 31%-heart failure diagnosis, 6%-history of carpal tunnel syndrome and 3%-spinal stenosis. ECHO: 26% had suggestive imaging, 43% with diastolic dysfunction, and 37% had a septal thickness >12mm. MRI: 42.9% had suggestive CA findings. No significant differences were found in the characteristics of suspicion between positive and negative patients. Regarding of the 35 patients scintigraphy, 7 (20%) were positives, establishing ATTR-CA diagnosis, 28 (80%) were negatives. The positivity probability was significant by H/Cl ratio, Perugini score, and SPECT findings (p 0.001). Until this protocol started and we share it among hospital physicians, we had never been asked to acquired this type of scintigraphy. Our study shows that if we purposely search for the disease, it can be found. The sample is small due to the limitations we had in the face of the pandemic; however, the study findings are significant for ATTR-CA diagnosis. It is striking that the ECHO and MRI suggestive findings were not statistically significant for the diagnosis. ConclusionsWe present the initial experience of the first study of cardiac amyloidosis in our country, to show the disease"s presence and that the diagnosis can be made effectively, quickly, economically, and non-invasively by nuclear medicine scintigraphy. Figure. 99mTc-PYP scan positive to ATTR-CA Figure. Patients characteristics

2021 Advocacy Statements for the Role of 99mTc-Pyrophosphate Scintigraphy in the Diagnosis of Transthyretin Cardiac Amyloidosis: A Report of the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China.

Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure with preserved ejection fraction. Favorable prognosis depends on early diagnosis and correct treatment strategy. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, 99mTc-labeled bone avid scintigraphy including 99mTc-pyrophosphate (PYP) scintigraphy may be of diagnostic and prognostic importance. Various international guidelines support the non-biopsy diagnosis of ATTR-CM using 99mTc-PYP scintigraphy, yet emphasize the gap in standardization of acquisition and imaging analysis protocols, as well as the appropriateness of its clinical use. Therefore, a joint expert consensus has been reached by the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China, to advocate for the application of 99mTc-PYP scintigraphy in the diagnosis of ATTR-CM. This article aims to highlight the recommendations on image acquisition, qualitative and quantitative assessments of cardiac 99mTc-PYP uptake, and diagnostic algorithms. We hope the implementation of these recommendations in Taiwan will facilitate the process and enhance the diagnostic rate of ATTR-CM.

Challenges in Diagnosis and Treatment of Systemic Amyloidosis: 10 Years of Experience in a Public Brazilian University Center

Systemic Amyloidosis (SA) results from tissue deposition of insoluble protein fibrils leading to organ dysfunction. Considering the scarcity of data from Latin America, a retrospective study was conducted by reviewing medical records of patients with biopsy proven SA diagnosed from 2009 to 2018 at a public tertiary center to assess clinical, laboratory and therapeutic features. Confirmed SA subtype was established if causative protein was identified on tissue biopsies by immunohistochemistry (IHC), indirect immunofluorescence (IIF), mass spectrometry (MS) or in the presence of pathogenic gene mutation related to SA. Probable cases were classified as light chain SA (AL) if evidence of monoclonal gammopathy (MG), transthyretin SA (ATTR) if moderate/strong cardiac uptake in 99mTc-pyrophosphate scintigraphy (99mTc-PYP), classical neurological symptoms with familial history or previous liver transplant from a donor with hereditary ATTR (hATTR), and secondary SA (AA) in the context of underlying chronic inflammatory disease. Inconclusive cases had ≥2 concomitant features suggestive of different subtypes. Primary endpoint was overall survival (OS). From 198 cases revised, 110 met the eligibility criteria. Median age was 60 years, 56% were male. Before diagnosis 53% were seen by ≥3 physicians: 65% general practitioners, 45% nephrologists, 42% cardiologists. Median time from onset of symptoms to diagnosis was 11.3 months. In 79% of patients ECOG was ≤2. Clinical presentations were: 54% renal disorders, 43% heart disease, 36% consumptive syndrome, 26% gastrointestinal symptoms, 25% neuropathy, 19% fatigue, 12% skin lesions, 9% hepatic disorders. The mean number of biopsies performed per patient was 2.3 and 60% had a method to subtype amyloid on biopsy: 67% IIF, 36% IHC and MS in 1 case. Mean number of affected organs was 2.6 (19% 1 organ, 38% 2 and 43% ≥ 3). Main organs were: 75% heart, 55% kidney, 43% soft tissue, 37% peripheral nervous system. Dialysis patients were 12%. Positive familial history was seen in 7% and 17% were tested for genetic mutations: 63% for transthyretin, 21% fibrinogen, 5% lysozyme, 16% MEFV gene. MG screening was assessed in 97% of patients, amyloid protein A in 4 and 99m Tc-PYP performed in 11. SA subtypes were confirmed in 32% of patients, probable in 59% and inconclusive in 9%. Frequency of subtypes were 68% AL, 12% ATTR, 6% AA, 4% fibrinogen amyloidosis (AFib), 1% lysozyme amyloidosis (ALys). Most of AL were λ (75%) and 34% had coexisting multiple myeloma. Standard Mayo Clinic Staging (MCS) was evaluated in 56% (59% stage III, 31% II, 10% I). Stage III were assessed by European staging (32% IIIa, 48% IIIb, 20% IIIc). Revised MCS was available in 21% (25% each I to IV). Renal staging showed 81% stages I/II, 19% stage III. Among ATTR patients 1 was wild type and 69% had mutation in TTR gene: 44% V30M, 33% V122I, 11% G89L. In 11% genetic data were not assessed. Mutated ATTR was presumed in 2 domino liver transplant recipients from hATTR donors. Inflammatory diseases in AA were: 43% Familial Mediterranean Fever (FMF), rheumatoid arthritis, vasculitis, immunoglobulin G4-related disease, combined polymyositis/primary biliary cholangitis (14% each). Treatments in AL were: 81% chemotherapy (CT) (54% melphalan, 18% thalidomide, 10% bortezomib), 12% stem cell transplant, 12% supportive measures (SM), 4% doxycycline, 1 kidney transplantation. Responses were available in 40 cases: 30% PR, 13% VGPR, 18% CR, 25% no response, 15% progression. ATTR was treated with: 31% liver transplantation, 54% SM, 8% tafamidis, 8% doxycycline. AA related to FMF treatments were anti-IL1 and colchicine and other AA received immunosuppressive therapy for underlying diseases. ALys was treated with SM. CT was given to 1 AFib patient before proper diagnosis, the others received SM. Inconclusive cases were managed 90% with SM, 1 received empirical CT. Median follow-up time of survivors was 66.3 months. At 5 years, estimated OS was 33%. Median OS in AL and non-AL were 18 and 74.4 months respectively (p &amp;lt; 0.001). In conclusion, the broad clinical spectrum of SA and the complex diagnostic approach lead to late diagnoses in advanced stages. Medical awareness of the disease, early suspicion, establishment of reference centers, better diagnostic tools, multidisciplinary team, a SA registry and access to disease-modifying drugs may result in early diagnosis and prompt intervention, improving outcomes in Brazil and Latin America. Disclosures No relevant conflicts of interest to declare.

Non-invasive detection and differentiation of cardiac amyloidosis using 99mTc-pyrophosphate scintigraphy and 11C-Pittsburgh compound B PET imaging

Purpose To investigate the utility of the combined use of 11C-Pittsburgh compound B (11C-PiB) positron emission tomography (PET) imaging and 99mTc-pyrophosphate (99mTc-PYP) scintigraphy for detection and differentiation of three major types of cardiac amyloidosis, i.e. immunoglobulin light chain (AL), hereditary transthyretin (ATTRv), and wild-type transthyretin (ATTRwt) amyloidosis. Methods Whole-body 11C-PiB PET and 99mTc-PYP scintigraphy were performed in 17 patients with AL amyloidosis, 22 patients with ATTRv, and eight patients with ATTRwt amyloidosis. The correlations between organ involvement and the uptake of 11C-PiB and 99mTc-PYP were analyzed in each patient. Results Cardiac amyloidosis was detectable by 99mTc-PYP scintigraphy or 11C-PiB PET in all systemic amyloidosis patients with cardiac involvement. 99mTc-PYP scintigraphy and 11C-PiB PET showed an interesting complementary relation. Strict combination of positive 11C-PiB and negative 99mTc-PYP uptake (PiB pattern) was observed in all AL amyloidosis patients with cardiac involvement. In contrast, strict combination of positive 99mTc-PYP and negative 11C-PiB uptake (PYP pattern) was observed in all ATTRwt amyloidosis patients with cardiac involvement. ATTRv amyloidosis patients with cardiac involvement were divided into two groups: PiB pattern or PYP pattern. All of the early-onset V30M (p.V50M) ATTRv patients showed the PiB pattern, whereas all of the late-onset V30M and non-V30M ATTRv patients showed the PYP pattern. Conclusions All three major types of cardiac amyloidosis can be detected and differentiated non-invasively by combined use of the two amyloid imaging methods and TTR gene testing.

Integrated diagnostic approach to wild-type transthyretin cardiac amyloidosis with the use of high-sensitivity cardiac troponin T measurement and 99mTc-pyrophosphate scintigraphy

BackgroundThe diagnosis of wild-type transthyretin cardiac amyloidosis (ATTRwt) is frequently missed or delayed because of the limited specificity of manifestations. We investigated the utility of combined assessment of high-sensitivity cardiac troponin T (hs-cTnT) measurement and 99mTc-pyrophosphate (99mTc-PYP) scintigraphy as diagnostic modalities in ATTRwt. MethodsWe divided 39 consecutive ATTRwt patients into two groups depending on whether serum hs-cTnT measurement and 99mTc-PYP scintigraphy were adopted as diagnostic tools: group A patients (n=8) who were diagnosed before the introduction of these two tools and group B patients (n=31) who were diagnosed after the introduction of the two tools. We retrospectively evaluated the two groups. ResultsDiagnostic yield was higher in group B than in group A (1.2 vs. 5.4 ATTRwt patients per 1000 hospitalized patients, p<0.01). Group B patients presented broad clinical features that were different from group A patients with classical characteristics. Atrial fibrillation was more frequent (12.5% vs. 58.1%, p=0.044) and inter-ventricular septum (IVS) thickness and relative wall thickness (RWT) were smaller in group B patients than in group A patients (IVS thickness: 16.1±2.4mm vs. 13.6±2.8mm, p=0.023; RWT: 0.71±0.11mm vs. 0.58±0.13mm, p=0.014). Furthermore, left ventricular hypertrophy (LVH) (IVS thickness ≥15mm) was more frequent in patients in group A than in patients in group B (87.5% vs. 33.3%, p=0.013). No significant difference was observed in the mean value of left ventricular ejection fraction (LVEF), whereas the dispersion of LVEF was high in group B (interquartile range: 47–58% vs. 39–57%). ConclusionsAn integrated approach consisting of hs-cTnT measurement and 99mTc-PYP scintigraphy significantly increases the diagnostic rate of ATTRwt and has a high potential to identify ATTRwt patients with a variety of clinical phenotypes.

O28-3 - A Case of Amyloid Cardiomyopathy Proved by Myocardial Biopsy but Diagnosed as Isolated Cardiac Sarcoidosis with Clinical Manifestations

A 74-year-old man with dyspnea on exertion was referred to our hospital for treatment of heart failure and evaluation of the cause. The symptom was immediately improved by medical therapy including oxygenation and diuretics. Electrocardiography showed frequent premature ventricular contraction with non-sustained ventricular tachycardia. Echocardiography revealed left ventricular (LV) dilatation (LV end-diastolic diameter/end-systolic diameter = 64/56 mm), thinning of the basal interventricular septum with severe hypokinesis of the region and LV systolic dysfunction (LVEF = 25%). Coronary angiography showed patent coronary artery. Late gadolinium enhancement in cardiac MR imaging was observed in septal to anterior wall. Furthermore, his lysozyme value was high (13.6 µg/mL). Cardiac sarcoidosis was strongly suspected, and 18F-fluorodeoxy glucose-positron emission tomography imaging showed lightly increased uptake in interventricular septum. Although he did not have the clinical findings other than heart, based on current guidelines for diagnosis and treatment of cardiac sarcoidosis (JCS 2016), a diagnosis of isolated cardiac sarcoidosis was finally made and we decided to start corticosteroid therapy with the initial dose of 30 mg/day of prednisolone. However, the specimens of myocardial biopsy revealed significant amount of transthyretin amyloid deposit. In addition 99mTc-pyrophosphate scintigraphy showed increased uptake by interventricular septum. In this case, there are two possibilities: first, all clinical manifestations due to transthyretin cardiac amyloidosis, and second, a chance complication with cardiac sarcoidosis and amyloid cardiomyopathy.

P581High prevalence of positive 99mTc-pyrophosphate scintigraphy in patients with non-ischemic and non-valvular heart failure over sixty years of age

P581High prevalence of positive 99mTc-pyrophosphate scintigraphy in patients with non-ischemic and non-valvular heart failure over sixty years of age

Nuclear medicine imaging with 99mTc-Pyrophosphate scintigraphy in patients with suspected cardiac amyloidosis

Nuclear medicine imaging with 99mTc-Pyrophosphate scintigraphy in patients with suspected cardiac amyloidosis

PREVALENCE OF TRANSTHYRETIN CARDIAC AMYLOIDOSIS IN PATIENTS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION USING THE 99MTC-PYROPHOSPHATE SCINTIGRAPHY

Background: The outcomes of patients with heart failure and preserved ejection fraction (HFpEF) have remained largely unchanged. Myocardial transthyretin amyloid deposition (ATTR) has been found in autopsy studies in up to 30% of patients with HFpEF. The 99mTc-pyrophosphate scintigraphy (PYP) scan

Circulation : Cardiovascular Imaging

<i>Circulation</i> : <i>Cardiovascular Imaging</i>

Effects of spironolactone on cardiac sympathetic nerve activity and left ventricular remodelling after reperfusion therapy in patients with first ST-segment elevation myocardial infarction

ObjectiveTo evaluate the effects of spironolactone on cardiac sympathetic nerve activity (CSNA) and left ventricular (LV) remodelling in patients with ST-segment elevation myocardial infarction (STEMI).DesignSingle-centre, prospective, randomised evaluation study.SettingPatients with...