<sup>99m</sup>Tc-DPD uptake reflects amyloid fibril composition in hereditary transthyretin amyloidosis

Pilebro, Björn; Suhr, Ole B.; Näslund, Ulf; Westermark, Per; Lindqvist, Per; Sundström, Torbjörn

doi:10.3109/03009734.2015.1122687

Cited by 93 publications

(63 citation statements)

References 37 publications

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“…Fibril type A is associated with a decreased LV myocardial function [14] and, in the present study, was also associated with decreased LA function and with increased atrial arrhythmic events. Although no differences in LA and LV myocardial function were found between ATTR patients with normal wall thickness and controls, those with septal thickness >12 mm displayed a smaller LA size and higher LASR during atrial systole, compared with those of HCM.…”

Section: Resultsmentioning

confidence: 49%

“…Amyloid fibril analysis also showed a close association between LV myocardial thickness and the type A ATTR fibrils. In Swedish hereditary ATTR V30M amyloidosis, there are two distinct fibril types [13,14,16,17]. Type A fibrils are composed mainly of N-terminally truncated TTR molecules starting at positions 46, 49 and 52 while type B fibrils consist of full-length TTR molecules.…”

Section: Resultsmentioning

confidence: 99%

“…It was possible to determine transthyretin amyloid fibril type (Type A ATTR fibrils consisting of fragmented and full length TTR and type B consisting of full length TTR only) in unfixed abdominal adipose tissue biopsies by gel electrophoresis and western blotting method, as previously described [13,14], in 36 patients.…”

Section: Amyloid Fibril Type Determinationmentioning

confidence: 99%

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Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis

Henein

Suhr

Arvidsson

et al. 2018

Amyloid

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Section: Resultsmentioning

confidence: 49%

Section: Resultsmentioning

confidence: 99%

Section: Amyloid Fibril Type Determinationmentioning

confidence: 99%

See 1 more Smart Citation

Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis

Henein

Suhr

Arvidsson

et al. 2018

Amyloid

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“…This mutation was presented during the International Symposium on Amyloidosis in Indianapolis in 2014 and subsequently included in the TTR mutations registry [2]. The clinical picture of ATTR amyloidosis in the two affected family members was foremost a late-onset cardiomyopathy [4,5,13]. Tc-diphosphonate scintigraphy is currently considered useful in clinical practice and more specific than ultrasound and CMR for noninvasive detection of an ATTR amyloid cardiomyopathy [9].…”

Section: Discussionmentioning

confidence: 99%

“…In 2016, another case with this TTR (p.A65G) mutation and amyloid cardiomyopathy was reported briefly [13]. These observations are in line with reports on all three other mutations of the same amino acid 65 of the TTR gene: (p.A65S), (p.A65T), and (p.A65D), in which the amino acid alanine (A) has been replaced by serine (S), threonine (T), and aspartic acid (D), respectively; therefore, all four mutations on this position 65 present as a cardiomyopathy [13,[16][17][18]. However, neurologic sequelae can be present and should be sought for.…”

Section: Discussionmentioning

confidence: 99%

Late onset cardiomyopathy as presenting sign of ATTR A45G amyloidosis caused by a novel TTR mutation (p.A65G)

Klaassen

Lemmink

Bijzet

et al. 2017

Cardiovascular Pathology

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Objective: The clinical description of a novel TTR gene mutation characterized by a late onset amyloid cardiomyopathy. Methods and Results: A 78-year-old man of Dutch origin with recent surgery for bilateral carpal tunnel syndrome (CTS) was admitted to our hospital because of heart failure with preserved ejection fraction (55%). Cardiac ultrasound showed thickened biventricular walls, and cardiac magnetic resonance imaging also showed late gadolinium enhancement. Early signs of a polyneuropathy were found by neurophysiological testing. A few months later, his 72-year-old sister was admitted to an affiliated hospital because of heart failure caused by a restrictive cardiomyopathy. In both patients, a subcutaneous abdominal fat aspirate was stained with Congo red and DNA was analyzed by direct sequencing of exons 1 to 4 of the transthyretin (TTR) gene. Both fat aspirates revealed transthyretin-derived (ATTR) amyloid. Tc-diphosphonate scintigraphy further confirmed cardiac ATTR amyloidosis in the male patient. DNA analysis of both patients showed a novel TTR mutation c.194C N G that encodes for the gene product TTR (p.A65G) ending up as the mature protein TTR A45G. The 56-year-old daughter of the male patient had the same TTR mutation. A full diagnostic workup did not reveal any signs of amyloidosis yet. Conclusions: A novel amyloidogenic TTR mutation was found in a Dutch family. The clinical presentation of ATTR A45G amyloidosis in the affected family members was heart failure due to a late-onset cardiomyopathy. The systemic nature of this disease was reflected by bilateral CTS and by early signs of a polyneuropathy in the index patient.

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Suspicion, screening, and diagnosis of wild‐type transthyretin amyloid cardiomyopathy: a systematic literature review

Bay¹,

Gustafsson

Maiborg

et al. 2022

ESC Heart Failure

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Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged by its unspecific and widely distributed clinical manifestations and traditionally invasive diagnostic tools. Recent advances in echocardiography and cardiac magnetic resonance (CMR), non-invasive diagnosis by bone scintigraphy, and the development of disease-modifying treatments have resulted in an increased interest, reflected in multiple publications especially during the last decade. To get an overview of the scientific knowledge and gaps related to patient entry, suspicion, diagnosis, and systematic screening of ATTRwt CM, we developed a framework to systematically map the available evidence of (i) when to suspect ATTRwt CM in a patient, (ii) how to diagnose the disease, and (iii) which at-risk populations to screen for ATTRwt CM. Articles published between 2010 and August 2021 containing part of or a full diagnostic pathway for ATTRwt CM were included. From these articles, data for patient entry, suspicion, diagnosis, and screening were extracted, as were key study design and results from the original studies referred to. A total of 50 articles met the inclusion criteria. Of these, five were position statements from academic societies, while one was a clinical guideline. Three articles discussed the importance of primary care providers in terms of patient entry, while the remaining articles had the cardiovascular setting as point of departure. The most frequently mentioned suspicion criteria were ventricular wall thickening (44/50), carpal tunnel syndrome (42/50), and late gadolinium enhancement on CMR (43/50). Diagnostic pathways varied slightly, but most included bone scintigraphy, exclusion of light-chain amyloidosis, and the possibility of doing a biopsy. Systematic screening was mentioned in 16 articles, 10 of which suggested specific at-risk populations for screening. The European Society of Cardiology recommends to screen patients with a wall thickness ≥12 mm and heart failure, aortic stenosis, or red flag symptoms, especially if they are >65 years. The underlying evidence was generally good for diagnosis, while significant gaps were identified for the relevance and mutual ranking of the different suspicion criteria and for systematic screening. Conclusively, patient entry was neglected in the reviewed literature. While multiple red flags were described, high-quality prospective studies designed to evaluate their suitability as suspicion criteria were lacking. An upcoming task lies in defining and evaluating at-risk populations for screening. All are steps needed to promote early detection and diagnosis of ATTRwt CM, a prerequisite for timely treatment.

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^99mTc-DPD uptake reflects amyloid fibril composition in hereditary transthyretin amyloidosis

Cited by 93 publications

References 37 publications

Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis

Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis

Late onset cardiomyopathy as presenting sign of ATTR A45G amyloidosis caused by a novel TTR mutation (p.A65G)

Suspicion, screening, and diagnosis of wild‐type transthyretin amyloid cardiomyopathy: a systematic literature review

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