Multidisciplinary Approaches for Transthyretin Amyloidosis

Koike, Haruki; Okumura, Takahiro; Murohara, Toyoaki; Katsuno, Masahisa

doi:10.1007/s40119-021-00222-w

Cited by 40 publications

(31 citation statements)

References 128 publications

(195 reference statements)

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“… 2 Hence, a multidisciplinary approach is on demand. 5 In the last years, several disease-modifying therapies have been developed: the actual scenario of current pharmaceutical approaches for ATTRv amyloidosis includes five main groups: TTR stabilizers (tafamidis, diflunisal, Epigallocatechin-3-Gallate, tolcapone, benzbromarone), TTR mRNA silencers (inotersen, patisiran, vutrisiran), TTR fibril disruptors (doxycycline, tauroursodeoxycholic acid, monoclonal antibodies), inhibitor of TTR fibril seeding and gene therapy. 2 , 6 …”

Section: Introductionmentioning

confidence: 99%

Italian Real-Life Experience of Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran

Stefano¹,

Fava²,

Gentile³

et al. 2022

PGPM

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Hereditary transthyretin amyloidosis (ATTRv) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensorimotor nerves, heart, autonomic function and other organs. The actual scenario of pharmaceutical approaches for ATTRv amyloidosis includes five main groups: TTR stabilizers, TTR mRNA silencers, TTR fibril disruptors, inhibitor of TTR fibril seeding and gene therapy. Patisiran is a small, double-stranded interfering RNA encapsulated in a lipid nanoparticle, able to penetrate into hepatocytes, where it selectively targets TTR mRNA, reducing TTR production. We report and discuss 9 cases of different patients with ATTRv amyloidosis successfully managed with patisiran in the real clinical practice. Literature data, as well as the above presented case reports, show that this drug is effective and safe in improving both neurological and cardiovascular symptoms of ATTRv amyloidosis, and to maintain a good QoL, independently form the stage of the disease and the involved mutation. Recent studies correlated improved functional and biochemical outcomes with a regression of amyloid burden, especially at the cardiac level. Today, patisiran can be considered a valid therapeutic option for the management of patients with ATTRv amyloidosis and polyneuropathy and cardiovascular symptoms.

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Section: Introductionmentioning

confidence: 99%

Italian Real-Life Experience of Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran

Stefano¹,

Fava²,

Gentile³

et al. 2022

PGPM

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“…The wide spectrum of symptoms observed at enrollment and the substantial proportion of patients with a mixed phenotype in this analysis emphasize the need for a multidisciplinary approach to the management of patients with all types of ATTR amyloidosis [ 33 ], and the importance of comprehensive evaluation, including neurologic, neurophysiological, and cardiac (electrocardiogram and echocardiogram) examinations. As evident in this study population, ATTR amyloidosis is a highly heterogeneous disease, and clinical manifestations can vary between different variants and/or geographic regions, and even between different family members who share the same pathogenic mutation.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update

Dispenzieri

Coelho

Conceição

et al. 2022

Orphanet J Rare Dis

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Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier: NCT00628745.

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“…Cardiac amyloidosis (CA) is a restrictive infiltrative cardiomyopathy and is associated with the worst prognosis among the amyloidotic pathologies. CA remains underdiagnosed and underestimated because it can occur with non-specific symptoms and is correlated with considerable mortality [1] . CA is caused by extracellular deposition of amyloidogenic proteins in the heart tissue; the most common amyloid proteins involved are amyloid light-chain (in AL amyloidosis) and transthyretin (TTR) in TTR amyloidosis (ATTR).…”

Section: Introductionmentioning

confidence: 99%

Clinical application of cardiac scintigraphy with bone tracers: controversies and pitfalls in cardiac amyloidosis

Mattana¹,

Muraglia²,

Girardi³

et al. 2022

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Cardiac amyloidosis (CA) is a life-threatening disease caused by extracellular deposition of amyloidogenic proteins in the heart tissue; it could be associated with a poor prognosis and remains underdiagnosed and underestimated. During the last years, bone scintigraphy has been widely used to facilitate the diagnosis of CA, avoid endomyocardial biopsy, and differentiate amyloid light-chain amyloidosis from transthyretin amyloidosis. Technetium-99m pyrophosphate (99mTc-PYP) is the most used tracer in the United States, but a standardized and shared acquisition protocol is still lacking; technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) is widely used in Europe and can count on a more grounded data than 99mTc-PYP. Both tracers suffer from some diagnostic limitations (due to their biochemical characteristics) and pitfalls that can lead to a misdiagnosis of CA. We aim to briefly describe the main differences between 99mTc-PYP and 99mTc-DPD, analyzing the data available in the literature and highlighting the most frequent causes of misdiagnosis and pitfalls. Both 99mTc-DPD and 99mTc-PYP show good accuracy for the diagnosis of CA with high specificity and sensibility. Nevertheless, to achieve this accuracy, the correct acquisition protocols must be followed for each tracer, as suggested in the latest recommendation. Proper diagnosis of CA has a crucial role in patient management; therefore, it is important for nuclear physicians to have the most specific approaches in acquiring and interpreting bone scintigraphy for transthyretin cardiac amyloidosis.

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Multidisciplinary Approaches for Transthyretin Amyloidosis

Cited by 40 publications

References 128 publications

Italian Real-Life Experience of Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran

Italian Real-Life Experience of Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran

Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update

Clinical application of cardiac scintigraphy with bone tracers: controversies and pitfalls in cardiac amyloidosis

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