Transthyretin Cardiac Amyloidosis: A Noninvasive Multimodality Approach to Diagnosis Using Transthoracic Echocardiography, 99m-Tc-Labeled Phosphate Bone Scanning, and Cardiac Magnetic Resonance Imaging.
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ABSTRACT:
SUBMITTER: Shukla A
PROVIDER: S-EPMC6034454 | biostudies-other | 2017 Apr
REPOSITORIES: biostudies-other
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Project description:BackgroundIncreasing recognition that transthyretin cardiac amyloidosis (ATTR-CA) is much more common than previously appreciated and the emergence of novel disease-modifying therapeutic agents have led to a paradigm shift in which ATTR-CA screening is considered in high-risk populations, such as patients with heart failure with preserved ejection fraction (HFpEF) or aortic stenosis. Radiation risk from 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, a test with very high sensitivity and specificity for ATTR-CA, has not been previously determined.Methods and resultsRadiation doses to individual organs from 99mTc-PYP were estimated using models developed by the Medical Internal Radiation Dose Committee and the International Commission on Radiological Protection. Excess future cancer risks were estimated from organ doses, using risk projection models developed by the National Academies and extended by the National Cancer Institute. Excess future risks were estimated for men and women aged 40-80 and compared to total (excess plus baseline) future risks. All-organ excess cancer risks (90% uncertainty intervals) ranged from 5.88 (2.45,11.4) to 12.2 (4.11,26.0) cases per 100,000 patients undergoing 99mTc-PYP testing, were similar for men and women, and decreased with increasing age at testing. Cancer risks were highest to the urinary bladder, and bladder risk varied nearly twofold depending on which model was used. Excess 99mTc-PYP-related cancers constituted?<?1% of total future cancers to the critical organs.ConclusionVery low cancer risks associated with 99mTc-PYP testing suggest a favorable benefit-risk profile for 99mTc-PYP as a screening test for ATTR-CA in high-risk populations, such as such as patients with HFpEF or aortic stenosis.
| S-EPMC6269210 | biostudies-literature
Project description:BackgroundIn [99mTc]Tc-DPD scintigraphy for myocardial ATTR amyloidosis, planar images 3 hour p.i. and SPECT/CT acquisition in L-mode are recommended. This study investigated if earlier planar images (1 hour p.i.) are beneficial and if SPECT/CT acquisition should be preferred in H-mode (180° detector angle) or L-mode (90°).MethodsIn SPECT/CT phantom measurements (NaI cameras, N = 2; CZT, N = 1), peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert (cardiac phantom; signal-to-background ratio [SBR], 10:1 or 5:1). In 25 positive and 38 negative patients (reference: endomyocardial biopsy or clinical diagnosis), Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i.ResultsIn phantom measurements, accuracy of myocardial CRpeak at SBR 10:1 (H-mode, 0.95-0.99) and reproducibility at 5:1 (H-mode, 1.02-1.14) was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader's confidence.ConclusionsEarly DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.
| S-EPMC8709821 | biostudies-literature
Project description:Porphyrin-lipid nanovesicles (PLN) have been developed with intrinsic capabilities as activatable multimodal photonic contrast agents. Radiolabeling of PLN encapsulating drugs could eventually be able to provide quantitative in vivo information for diagnosing and treating diseases. In this study, we developed (99m)Tc-labeled porphyrin-lipid nanovesicles ((99m)Tc-PLN) as a cargo-encapsulated formulation without significant impact on liposome integrity and encapsulation stability. 50?mM calcein was encapsulated into PLN by probe sonication. The size of the PLN was about 150?nm. The PLN were then reacted with (99m)Tc using SnCl2 dissolved in 1?mM HCl as a reducing agent and incubated for 10?min at 22?°C. The radiolabeling efficiency and stability of (99m)Tc-PLN were evaluated by instant thin-layer chromatography and low-pressure liquid chromatography (LPLC). (99m)Tc labeling was successful with a >92% labeling efficiency. LPLC showed that the liposomal elution peaks of the porphyrin-lipid and the calcein overlapped with the radioactivity elution peak of (99m)Tc-labeled PLN. The (99m)Tc-labeling procedure did not change the size of PLN. Encapsulated calcein remained inert inside PLN. Thus, this work lays out a simple and effective radiolabeling method using SnCl2 in HCl in the preparation of (99m)Tc-PLN.
| S-EPMC4276732 | biostudies-literature
Project description:Background99mTc-pyrophosphate imaging has emerged as an important non-invasive method to diagnose transthyretin cardiac amyloidosis (ATTR-CM). Quantitation of 99mTc-pyrophosphate activity, on SPECT images, could be a marker of ATTR-CM disease burden. We assessed the diagnostic accuracy and clinical significance of 99mTc-pyrophosphate quantitation.Methods and resultsPatients who underwent 99mTc-pyrophosphate imaging for suspected ATTR-CM were included. Using SPECT images, radiotracer activity in the myocardium was calculated using cardiac pyrophosphate activity (CPA) and volume of involvement (VOI), with thresholds for abnormal activity derived from LVBP activity. Diagnostic accuracy was assessed using area under the receiver operating characteristic curve (AUC). In total, 124 patients were identified, mean age 73.9 ± 11.4, with ATTR-CM diagnosed in 43 (34.7%) patients. CPA had the highest diagnostic accuracy (AUC .996, 95% CI .987-1.00), and was significantly higher compared to the Perugini score (AUC .952, P = .016). In patients with ATTR-CM, CPA was associated with reduced left ventricular ejection fraction (adjusted odds ratio 1.28, P = .035) and heart failure hospitalizations (adjusted hazard ratio 1.29, P = .006).ConclusionQuantitative assessment of myocardial radiotracer activity with CPA or VOI have high diagnostic accuracy for ATTR-CM. Both measures are potential non-invasive markers to follow progression of disease or response to therapy.
| S-EPMC8497047 | biostudies-literature
Project description:Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with (99m)Tc-HMPAO under physiologic conditions and monitored in vivo distribution of (99m)Tc-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with (99m)Tc-HMPAO for 1?hr incubation, followed by removal of free (99m)Tc-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with (99m)Tc-HMPAO, the radiochemical purity of (99m)Tc-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in (99m)Tc-HMPAO-ENVs. (99m)Tc-HMPAO-ENVs showed high serum stability (90%) which was similar to that in phosphate buffered saline until 5?hr. SPECT/CT images of the mice injected with (99m)Tc-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with (99m)Tc-HMPAO showed high brain uptake until 5?hr. Our noninvasive imaging of radiolabeled-ENVs promises better understanding of the in vivo behavior of exosomes for upcoming biomedical application.
| S-EPMC4620485 | biostudies-literature
Project description:AIMS:Left ventricular ejection fraction (LVEF) is the most frequently used parameter in the assessment of heart failure (HF). Cardiac index (CI) is considered a potential alternative to LVEF despite limited evidence. We aimed to assess and compare the predictive accuracy of LVEF and echocardiographically-assessed CI in HF patients. METHODS AND RESULTS:A single-centre, retrospective cohort study was conducted in patients hospitalized for acute HF from 2010-2016. Cox proportional hazard models including either LVEF or CI were created to predict all cause death, cardiovascular (CV) death, or first HF-readmission. Of 334 patients included in the analysis, 58.7% exhibited HF with reduced LVEF (HFrEF). Left ventricular ejection fraction did not show correlation with any endpoint, while CI was predictive of HF-readmission in the entire cohort. Both the LVEF-based and CI-based models demonstrated moderate discriminative accuracy when predicting all-cause death, CV death, or HF-readmission. Left ventricular ejection fraction proved to be an independent predictor of CV mortality in HFrEF-patients, while CI was predictive of HF-readmission in the non-HFrEF group. CONCLUSIONS:Left ventricular ejection fraction seemed to be associated more closely with disease severity in HFrEF, and CI in the non-HFrEF group, in this real-life cohort of elderly HF patients. The LVEF-based and CI-based predictive models have clinically similar predictive accuracy for mortality and HF-readmission, thus CI may be a potential alternative to LVEF in the assessment of left ventricular function. Cardiac index may be an important new tool in the assessment of HF patients with midrange or preserved LVEF.
| S-EPMC6291087 | biostudies-literature
Project description:Transthyretin-related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive and hypertrophic heart disease and often goes undiagnosed. In the United States, the hereditary form disproportionately afflicts black Americans, who when compared with whites with wild-type transthyretin amyloidosis, a phenotypically similar condition, present with more advanced disease despite having a noninvasive method for early identification (genetic testing). Although reasons for this are unclear, this begs to consider the inadequate access to care, societal factors, or a biological basis. In an effort to improve awareness and explore unique characteristics, we review the pathophysiology, epidemiology, and therapeutic strategies for transthyretin amyloidosis and highlight diagnostic pitfalls and clinical pearls for identifying patients with amyloid heart disease.
| S-EPMC4874558 | biostudies-literature
Project description:Wild-type transthyretin cardiac amyloidosis (ATTRwt), formerly called senile cardiac amyloidosis (SCA), is almost exclusively a disorder of older adults. As the population ages, the diagnosis of ATTRwt will increase, making it the most common form of cardiac amyloidosis. An important precondition to reduce underdiagnosis and misdiagnosis is to maintain a high index of suspicion for cardiac amyloidosis. Several clues can be gleaned from the clinical history, physical exam, electrocardiography, and noninvasive imaging techniques. Nuclear scintigraphy agents using 99mTc-phosphate derivatives combined with assessment for monoclonal proteins are eliminating the need for tissue confirmation in ATTR. Morbidity and mortality from ATTRwt cardiac amyloid is high and the emergence of numerous therapies based on a biologic understanding of the pathophysiology of this condition, including drugs to inhibit the synthesis of TTR, stabilize TTR, and degrade or extract amyloid, provides new hope for those afflicted. This review briefly covers the epidemiology, pathophysiology, and clinical manifestations, as well as diagnostic strategies and treatment, of ATTR in older adults.
| S-EPMC5127719 | biostudies-literature
Project description:Background: Amyloid transthyretin (ATTR) cardiac amyloidosis has now been recognized as one of the major causes of heart failure, especially in elderly patients. The purpose of the present study was to validate the usefulness of technetium-99 m (99 mTc)-pyrophosphate (99 mTc-PYP) scintigraphy in the screening diagnosis for ATTR amyloidosis in daily clinical practice. Methods and Results: Ninety-eight patients underwent 99 mTc-PYP scintigraphy in the previous 3 years (PYP positive/negative, 18/80), of whom 29 underwent concomitant endomyocardial biopsy (ATTR positive/negative, 9/20). The sensitivity and specificity of 99 mTc-PYP scintigraphy for the diagnosis of biopsy-proven ATTR amyloidosis were 0.889 and 0.950, respectively. Age, gender, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, or electrocardiogram findings did not differ significantly between PYP-positive and PYP-negative patients. Left ventricular (LV) wall thickness was significantly greater in PYP-positive than in PYP-negative patients, but LV ejection fraction or prevalence of atrial fibrillation was similar between groups. In the PYP-positive patients, higher uptake of PYP correlated with younger age and lower NT-proBNP. Conclusions: 99 mTc-PYP scintigraphy was useful, with high sensitivity and specificity in the screening diagnosis for ATTR cardiac amyloidosis, which is difficult to diagnose on clinical characteristics alone. 99 mTc-PYP scintigraphy should be considered to elucidate the underlying causes of heart failure, especially in elderly patients based on the higher prevalence of ATTR cardiac amyloidosis in this population.
| S-EPMC7892493 | biostudies-literature
Project description:AimsCardiac transthyretin amyloidosis (ATTR-CM) is a progressive and fatal condition. Prognosis can be determined at diagnosis according to the National Amyloidosis Centre (NAC) transthyretin amyloidosis (ATTR) stage. We sought to examine how NAC ATTR stage changes during follow-up and whether it maintains its prognostic value throughout the disease course.Methods and resultsWe performed a retrospective study of 945 patients with wild-type ATTR-CM (wtATTR-CM) or hereditary ATTR-CM associated with the V122I variant (V122I-hATTR-CM) who were diagnosed and serially evaluated at the UK NAC. Patients who commenced any disease-modifying therapy for amyloidosis were censored at the time of doing so. Landmark Kaplan-Meier survival analyses were performed at diagnosis (n = 945) and at 6 ± 1 (n = 432), 12 ± 3 (n = 562), and 24 ± 3 (n = 316) months and stratified by recalculated NAC ATTR stage at the relevant time point. Cox regression analyses were performed to assess the prognostic significance during follow-up of an increase in NAC ATTR stage from Stage I at diagnosis. Mortality in ATTR-CM was predicted by NAC ATTR stage at each time point [Stage II vs. I, hazard ratios (HRs) 1.95-2.67; P < 0.001; Stage III vs. II, HRs 1.64-2.25; P < 0.001-0.013]. An increase from NAC ATTR Stage I, which occurred in 21%, 32%, and 44% of evaluable patients at 6, 12, and 24 months of follow-up respectively, was highly predictive of ongoing mortality at each time point (HRs 2.58-3.22; P < 0.001) and in each genotypic subgroup (HRs 1.86-4.38; P < 0.05). Increase in NAC ATTR stage occurred earlier in V122I-hATTR-CM than in wtATTR-CM (43% vs. 27% at 12 months of follow-up; P = 0.003).ConclusionsNational Amyloidosis Centre ATTR stage predicts ongoing survival throughout the disease natural history in ATTR-CM, and an increase from NAC ATTR Stage I at diagnosis to a higher NAC ATTR stage predicts mortality throughout follow-up. Serial calculation of NAC ATTR stage suggests a more aggressive phenotype in V122I-hATTR-CM than in wtATTR-CM.
| S-EPMC7755026 | biostudies-literature