Diagnostic accuracy of bone scintigraphy in the assessment of cardiac transthyretin-related amyloidosis: a bivariate meta-analysis

Treglia, Giorgio; Glaudemans, Andor W J M; Bertagna, Francesco; Hazenberg, Bouke P. C.; Erba, Paola Anna; Giubbini, Raffaele; Ceriani, Luca; Prior, John O.; Giovanella, Luca; Slart, Riemer H. J. A.

doi:10.1007/s00259-018-4013-4

Cited by 111 publications

(88 citation statements)

References 54 publications

(118 reference statements)

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“…The diagnostic performance of CMR and nuclear scintigraphy has been reported in individual studies and in single‐modality meta‐analyses . However, the reference histopathological tests have included a combination of cardiac and extra‐cardiac tissue samples, and the results of different techniques using the same imaging modality have been pooled in analyses.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta‐analysis

et al. 2019

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AimsThe study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis.Methods and resultsMEDLINE and Embase electronic databases were searched for studies evaluating the diagnostic performance of CMR or nuclear scintigraphy in detecting cardiac amyloidosis and subsequently in differentiating transthyretin amyloidosis (ATTR) from immunoglobulin light‐chain (AL) amyloidosis. In this meta‐analysis, histopathological examination of tissue from endomyocardial biopsy (EMB) or extra‐cardiac organs were reference standards. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated, and a random effects meta‐analysis was used to estimate diagnostic odds ratios. Methodological quality was assessed using a validated instrument. Of the 2947 studies identified, 27 met the criteria for inclusion. Sensitivity and specificity of CMR in diagnosing cardiac amyloidosis was 85.7% and 92.0% against EMB reference and 78.9% and 93.9% with any organ histology reference. Corresponding sensitivity and specificity of nuclear scintigraphy was 88.4% and 87.2% against EMB reference and 82.0% and 98.8% with histology from any organ. CMR was unable to reliably differentiate ATTR from AL amyloidosis (sensitivity 28.1–99.0% and specificity 11.0–60.0%). Sensitivity and specificity of nuclear scintigraphy in the differentiation of ATTR from AL amyloidosis ranged from 90.9% to 91.5% and from 88.6% to 97.1%. Pooled negative likelihood ratio and positive likelihood ratio for scintigraphy in this setting were 0.1 and 8, with EMB reference standard. Study quality assessed by QUADAS‐2 was generally poor with evidence of bias.ConclusionsCardiac magnetic resonance is a useful test for diagnosing cardiac amyloidosis but is not reliable in further classifying the disease. Nuclear scintigraphy offers strong diagnostic performance in both the detection of cardiac amyloidosis and differentiating ATTR from AL amyloidosis. Our findings support the use of both imaging modalities in a non‐invasive diagnostic algorithm that also tests for the presence of monoclonal protein.

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Section: Introductionmentioning

confidence: 99%

Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta‐analysis

et al. 2019

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“…Не так давно выполненный двумерный мета-анализ также подтвердил точность сцинтиграфии при оценке ATTR АС [12]. Объяснение настолько разного поглощения при транстиретиновом амилоидозе сердца в отличие от амилоидоза легких цепей неизвестно, но высказано предположение, что интенсивное накопление изотопов при TTR поражении может быть результатом более высокого содержания кальция [9].…”

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Molecular Imaging

Editorial¹

2020

Lučevaâ diagn. ter.

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“…61 A possibility to detect ATTRm or ATTRwt is by application of the 99mTcDPD SPECT, which highly sensitive for TTR-CA. 63 If the MIBG-SPECT is inconclusive and the heart the only clinically affected organ, endomyocardial biopsy should be considered. MIBG scintigraphy proved to be a strong and independent prognostic marker of poor outcome in ATTRm amyloidosis.…”

Section: Cardiac Involvementmentioning

confidence: 99%

“…MIBG scintigraphy proved to be a strong and independent prognostic marker of poor outcome in ATTRm amyloidosis. 63 If the MIBG-SPECT is inconclusive and the heart the only clinically affected organ, endomyocardial biopsy should be considered.…”

Section: Genetic Testsmentioning

confidence: 99%

Hereditary transthyretin-related amyloidosis

et al. 2018

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Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early-and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation. TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Neuropathy may not only include large nerve fibers but also small fibers, and not only sensory and motor fibers but also autonomic fibers. Types of TTR variants, age at onset, penetrance, and clinical presentation vary between geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy, carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy. If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues. Diagnostic tests for small fiber neuropathy include determination of intraepidermal nerve fiber density, laser-evoked potentials, heat-and cold-detection thresholds, and measurement of the electrochemical skin conductance. Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis, diflunisal). K E Y W O R D Samyloid, neuropathy, small fiber, tafamidis, transplantation, transthyretin | 93 FINSTERER ET al. eyes, the gastrointestinal tract, the kidneys, and the skin. ATTRm amyloidosis is resistant to immunotherapy. Though ATTRm-related polyneuropathy or TTR-CA may occur without affection of another tissue, a variable combination of organ affection (multiorgan involvement) is the most frequent phenotype. This review aims at summarizing and discussing previous and recent findings concerning the clinical presentation, genetic background, pathogenesis, diagnosis, treatment, and outcome of ATTRm-related polyneuropathy. | ME THODSData for this review were identified by searches of MEDLINE for references of relevant articles. Search terms applied were "transthyretin," "gene," "TTR-FAP," or "mutation," combined with "neuropathy," "hereditary," "autonomic," "small fiber neuropathy," and "polyneuropathy." Results of the search were screened for potentially relevant studies by application of inclusion and exclusion criteria for the full texts of the relevant studies. Included were randomized controlled trials (RCTs), observational studies with controls, case series, and case reports. Only original articles about humans, and published between 1966 and 2018 were included. Reviews, editorials, and letters were not considered. Reference lists of retrieved studies were checked for reports of additional studies. Websites checked for additional, particularly geneti...

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Diagnostic accuracy of bone scintigraphy in the assessment of cardiac transthyretin-related amyloidosis: a bivariate meta-analysis

Abstract: Our evidence-based data demonstrate that bone scintigraphy using technetium-labelled radiotracers provides very high diagnostic accuracy in the non-invasive assessment of cardiac ATTR.

Cited by 111 publications

References 54 publications

Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta‐analysis

Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta‐analysis

Molecular Imaging

Hereditary transthyretin-related amyloidosis

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