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Comparison of the soft tissue tracer uptake of subcutaneous fat in the left axillar region in patients with vs without PNP using DPD SPECT/CT scintigraphy. (a) In the subgroup of the 22 patients with quantitative thoracic SPECT/CT the soft tissue tracer uptake of subcutaneous fat in the left axillar region was significantly increased in patients with PNP compared to patients without PNP (1.41 ± 0.58 vs 0.84 ± 0.58; P = 0.04). (b) After exclusion of patients with diabetes the soft tissue tracer uptake of subcutaneous fat in the left axillar region was still significantly increased in patients with PNP compared to patients without PNP (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04).
Source publication
Background
With the introduction of several drugs for the therapy of transthyretin-related amyloidosis (ATTR) which slow down the disease, early detection of polyneuropathy (PNP) is becoming increasingly of interest. [99mTc]-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) bone scintigraphy, which is used for the diagnosis of cardiac (c)ATTR, can...
Contexts in source publication
Context 1
... SPECT/CT subgroup analysis (group 5) showed a significantly increased DPD uptake of the subcutaneous fat in the left axillar region in cATTR patients with PNP compared to patients without (1.41 ± 0.58 vs 0.84 ± 0.58; P = 0.04). After excluding patients with diabetes ST uptake further increased significantly (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04, Fig. 3). Representative SPECT/CT images of hATTR and wtATTR patients with and without PNP are shown in Online Resource Fig. ESM3. The additional SPECT/ CT subgroup analysis of 14 wtATTR patients did not reveal any significant difference of SUVpeak in the subcutaneous fat of the left axillar region in patients with compared to patients without ...
Context 2
... region in cATTR patients with PNP compared to patients without (1.41 ± 0.58 vs 0.84 ± 0.58; P = 0.04). After excluding patients with diabetes ST uptake further increased significantly (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04, Fig. 3). Representative SPECT/CT images of hATTR and wtATTR patients with and without PNP are shown in Online Resource Fig. ESM3. The additional SPECT/ CT subgroup analysis of 14 wtATTR patients did not reveal any significant difference of SUVpeak in the subcutaneous fat of the left axillar region in patients with compared to patients without PNP (1.19 ± 0.65 vs 0.53 ± 0.37; P = 0.06), even after exclusion of patients with diabetes (1.17 ± 0.66 vs 0.53 ± 0.37; P ...
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Citations
... For reliable diagnosis of TTR neuropathy, easily accessible, non-invasive, and sensitive biomarkers for amyloid neuropathy are essential. Soft-tissue uptake in DPD scintigraphy has been suggested to correlate with myopathy 9 and neuropathy in A-ATTR 36 , although localization to single peripheral nerves is difficult and would require SPECT/CT imaging, which is seldom performed in the lower extremity 37 . Therefore, although some results of our study may suggest it, a causal association of amyloidosis and neuropathy remains uncertain. ...
In contrast to inherited transthyretin amyloidosis (A-ATTRv), neuropathy is not a classic leading symptom of wild type transthyretin amyloidosis (A-ATTRwt). However, neurological symptoms are increasingly relevant in A-ATTRwt as well. To better understand the role of neurological symptoms in A-ATTRwt, A-ATTRwt patients were prospectively characterized at Amyloidosis Center Charité Berlin (ACCB) between 2018 and 2023 using detailed neurological examination, quality of life questionnaires, and analysis of age- and BMI-adapted serum neurofilament light chain (NFL) levels. 16 out of 73 (21.9%) patients presented with a severe neuropathy which we defined by a Neuropathy Impairment Score (NIS) of 20 or more. In this group, quality of life was reduced, peripheral neuropathy was more severe, and spinal stenosis and joint replacements were frequent. Age- and BMI matched serum NFL levels were markedly elevated in patients with a NIS ≥ 20. We therefore conclude that highly abnormal values in neuropathy scores such as the NIS occur in A-ATTRwt, and have an important impact on quality of life. Both peripheral neuropathy and spinal canal stenosis are likely contributors. Serum NFL may serve as a biomarker for neurological affection in patients with A-ATTRwt. It will be important to consider neurological aspects of A-ATTRwt for diagnosis, clinical follow-up, and future treatment development.
... Also, an in-vitro study showed a higher affinity of [ 99m Tc]Tc-DPD for amyloid fibrils than [ 99m Tc]Tc-HMDP or [ 99m Tc]Tc-PYP [25]. Wollenweber and al. suggest that [ 99m Tc]Tc-DPD scintigraphy is useful to detect patients with a higher risk for polyneuropathy associated to ATTR-CM [26]. Regrettably, we were unable to assess the binding ratio of the two tracers concerning the causal mutation, as such investigations are exceedingly rare in the context of positive scintigraphy. ...
Background
The management of transthyretin amyloid cardiomyopathy (ATTR-CM) has revolved around the scintigraphic diagnosis since the introduction of a specific treatment; however, the equivalency of the bone radiotracers remains unclear. This retrospective monocentric observational study compared [99mTc]Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ([99mTc]Tc-DPD) and [99mTc]Tc-hydroxy-methylene diphosphonate ([99mTc]Tc-HMDP) for ATTR-CM diagnosis.
Methods
One hundred and twenty-nine patients who underwent single photon emission computed tomography (SPECT/CT) after intravenous injection of [99mTc]Tc-DPD or [99mTc]Tc-HMDP for ATTR-CM were included. The patients' current visual Perugini grades were retrieved. Regions of interest (ROI) were measured on the heart (H) and on contralateral mediastinum (CM), and H/CM ratios were calculated.
Results
Although the distribution of quantitative assessments of heart to contralateral mediastinum ratios is wider with [99mTc]Tc-DPD, suggesting a trend towards improved diagnosis, no difference in Perugini grades was found between [99mTc]Tc-DPD or [99mTc]Tc-HMDP for the diagnosis of ATTR-CM in evocative/non-evocative conditions. There was no difference in ATTR-CM diagnosis between the 2 tracers with a threshold of 1.5 (p-value = 3.316*10-10 for [99mTc]Tc-HMDP and p-value = 2.59*10-15 for [99mTc]Tc-DPD).
Conclusions
We show in our local cohort that [99mTc]Tc-DPD and [99mTc]Tc-HMDP for amyloidosis diagnostic are equivalent for ATTR-CM diagnosis based on the Perugini grading scale. With [99mTc]Tc-DPD, a wider range of the H/CM ratio was noted, which may be considered as a better discrimination of the disease by this bone tracer. Additional research with a final diagnosis of the disease is necessary to evaluate the utility of this quantitative evaluation.
... 8 Quantitative SPECT/CT of the thorax revealed that Tc-99m DPD uptake in the subcutaneous fat tissue of the left axillar region was significantly increased in ATTR-CA patients with polyneuropathy compared to those without. 9 In comparison to Tc-99m HMDP and Tc-99m DPD, extra-cardiac uptake of Tc-99m PYP is less commonly observed and the literature is largely limited to case reports or case series. The current study is a muchwelcome addition to the accumulating literature on extra-cardiac uptake of Tc-99m PYP. ...
... 99m The patient underwent a technetium-99m ( Tc)-DPD bone scintigraphic study 3 hours post injection (Whole body, Planar images of the thorax and myocardial SPECT imaging), which revealed increased uptake in the heart muscle (>>>ribs), indicative of ATTR-CA (grade III) according to Perugini visual score ( Figure 4). Soft tissues had signi cant uptake, which matches bibliographic reports of ATTR amyloidosis with neurological involvement [12]. There was also uptake by the lungs. ...
Objective:
Transthyretin cardiac amyloidosis (ATTR-CA) is a rare and potentially fatal disease caused by the accumulation of insoluble transthyretin (TTR) amyloid fibrils in the heart. The symptoms of ATTR-CA are often non-specific, often leading to underdiagnosis. Early diagnosis and treatment have a significant impact on disease progression and mortality.
Case presentation:
In this case we report a 73-year-old male presented with dyspnea on exertion. The patient had a medical history of peripheral neuropathy, bilateral carpal tunnel syndrome, spinal fusion, and a family history of coronary artery disease. Upon his presentation at the Cardiology department, cardiac echo study revealed left and right ventricular hypertrophy with pulmonary hypertension, diastolic dysfunction and a restrictive pattern. Because of the high probability of amyloidosis, the patient underwent a technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphic study, which confirmed the diagnosis of ATTR-CA. Transthyretin gene sequencing analysis revealed the rare p. Pro24Ser pathogenic variant. Final diagnosis was ATTR-CA associated with the proline replaced by serine at position 24 (Pro24Ser) TTR variant, which is rare and only a few cases have been reported worldwide. The patient was treated with tafamidis and inotersen and followed up.
Conclusion:
This case highlights the importance of considering amyloidosis as a differential diagnosis for non-specific symptoms and the need for early diagnosis and management of ATTR-CA.
... 13 In this issue of the Journal of Nuclear Cardiology, Wollenweber et al. reported the potential utility of increased [ 99m Tc]-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) soft tissue uptake to serve as an imaging marker that identifies patients with ATTR-CA at a higher risk for having concomitant PNP. 14 The authors of this study hypothesized that there would be higher soft tissue DPD uptake in ATTR-CA patients with PNP as compared to ATTR-CA patients without PNP. In this retrospective, single center study, a cohort of 50 patients with ATTR-CA (41 wild-type and 9 hereditary) who had undergone whole body DPD scintigraphy and a nerve conduction study (NCS) were evaluated. ...
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.
Amyloidoses are a complex group of clinical diseases that result from progressive organ dysfunction due to extracellular protein misfolding and deposition. The two most common types of cardiac amyloidosis are transthyretin amyloidosis (ATTR) and light chain (AL) amyloidosis. The diagnosis of ATTR cardiomyopathy (ATTR-CM) is challenging due to its phenotypic similarity to other more common cardiac conditions, perceived rarity of the disease, and unfamiliarity with its diagnostic algorithms; endomyocardial biopsy was historically required for diagnosis. However, myocardial scintigraphy using bone-seeking tracers has shown high accuracy for detection of ATTR-CM and has become a key noninvasive diagnostic test for the condition, being supported by professional society guidelines and transforming prior diagnostic paradigms. This AJR Expert Panel Narrative Review describes the role of myocardial scintigraphy using bone-seeking tracers in the diagnosis of ATTR-CM. The article summarizes available tracers, acquisition techniques, interpretation and reporting considerations, diagnostic pitfalls, and gaps in the current literature. The critical need for monoclonal testing in patients with positive scintigraphy results to differentiate ATTR-CM and AL cardiac amyloidosis is highlighted. Recent updates in guideline recommendations that emphasize the importance of a qualitative visual assessment are also discussed.
Background
Bone scintigraphy plays an important role in the diagnosis of cardiac Transthyretin-Related Amyloidosis (ATTR). The mechanism of myocardial tracer accumulation and its dependence over time are not fully understood. Recently, a scintigraphic quantification of the cardiac amyloid deposition has been discussed. Nevertheless, little is known regarding the right time of quantitative imaging.
Methods
The geometrical mean of decay corrected total counts over the heart and the heart/whole-body ratio (H/WB) were evaluated in 23 patients undergoing DPD-bone scan with planar whole-body images 1 and 3 hours post injection (p.i.). Myocardial standard uptake values (SUV)peak were assessed in another 15 patients with quantitative SPECT/CT imaging 1 hours and 3 hours p.i..
Results
Total counts over the heart (1 hours p.i.: 81,676 cts, range 69,887 to 93,091 cts and 3 hours p.i.: 64,819 cts, range 52,048 to 86,123 cts, P = .0005) and H/WB ratio (1 hours p.i.:0.076 ± 0.020 and 3 hours p.i. 0.070 ± 0.022; P = .0003) were significantly increased 1 hours p.i.. Furthermore median myocardial SUVpeak (1 hours p.i.:12.2, range 9.6 to 18.9 and 3 hours p.i.: 9.6, range 8.2 to 15.0, P = 0.0012) was also significantly higher after 1 hours p.i. compared to 3 hours p.i..
Conclusion
Cardiac DPD activity and myocardial SUVpeak are time-dependent, which should be considered when using quantitative bone scintigraphy in ATTR patients.
