Cardiac amyloidosis: from clinical suspicion to morphological diagnosis

Flodrova, Pavla; Flodr, Patrik; Pika, Tomáš; Vymětal, Jiří; Holub, Dušan; Džubák, Petr; Hajdúch, Marián; Scudla, Vlastimil

doi:10.1016/j.pathol.2017.10.012

Cited by 26 publications

(29 citation statements)

References 76 publications

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“…38 While the heart is a target of several types of amyloid, more than 95% of cases are due to AL and ATTR. 5,37,39,40 It has been estimated that 20% to 35% of those with a lightchain paraprotein develop amyloid, while between 50% and 90% of those with AL amyloid have cardiac involvement, 41,42 making this the most common form found in the heart. The pattern of AL amyloid deposition is usually subendocardial and diffuse in a reticular/pericellular pattern.…”

Section: Heartmentioning

confidence: 99%

An Organ System–Based Approach to Differential Diagnosis of Amyloid Type in Surgical Pathology

Giannini

Nast

2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Amyloidosis is an uncommon but important entity. A protein-based classification of amyloidosis defines the underlying disease process, directing clinical management and providing prognostic information. However, in routine surgical pathology there often is no attempt to classify amyloid other than staining to determine light chain–associated amyloidosis. Systemic and localized amyloidosis vary with respect to frequency of organ involvement by different amyloid types, and most amyloid proteins have commercial antibodies available for identification. Objective.— To provide a guide for the likelihood of amyloid type by organ system. Data Sources.— Literature review based on PubMed searches containing the word amyloid, specifically addressing the prevalence and significance of amyloid proteins in each organ system other than the brain, and the authors' practice experience. Conclusions.— In patients with amyloidosis, determination of the responsible protein is critical for appropriate patient care. In large subspecialty practices and reference laboratories with experience in using and analyzing relevant immunohistochemistry, most amyloid proteins can be identified with an organ-specific algorithm. Referring to an organ-based algorithm may be helpful in providing clinicians with a more specific differential diagnosis regarding amyloid type to help guide clinical evaluation and treatment. When the protein cannot be characterized, mass spectrometry can be performed to definitively classify the amyloid type.

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Section: Heartmentioning

confidence: 99%

An Organ System–Based Approach to Differential Diagnosis of Amyloid Type in Surgical Pathology

Giannini

Nast

2019

Archives of Pathology &Amp; Laboratory Medicine

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“…46 Without treatment, patients die from progressive organ dysfunction, particularly heart failure, infection, or cachexia approximately within 10 years of disease onset. 2 In a recent retrospective study of 120 patients with TTR-CA of whom 29 received tafamidis, application of TTRstabilizers was associated with decreased rate of orthotopic heart transplantation and death. 2 In a recent retrospective study of 120 patients with TTR-CA of whom 29 received tafamidis, application of TTRstabilizers was associated with decreased rate of orthotopic heart transplantation and death.…”

Section: Prognosis and Outcomementioning

confidence: 99%

“…8 Cardiac involvement is the most important prognostic factor in patients with generalized amyloidosis. 2 In a recent retrospective study of 120 patients with TTR-CA of whom 29 received tafamidis, application of TTRstabilizers was associated with decreased rate of orthotopic heart transplantation and death. 85 Another major factor influencing the survival rate of ATTRm amyloidosis patients is the TTR genotype.…”

Section: Prognosis and Outcomementioning

confidence: 99%

“…2 If biopsy findings are negative but ATTRm amyloidosis is still suspected, it is recommended to perform sequencing of the TTR gene. 2 If biopsy findings are negative but ATTRm amyloidosis is still suspected, it is recommended to perform sequencing of the TTR gene.…”

Section: Biopsymentioning

confidence: 99%

“…1 More than 30 different abnormal proteins involved in the generation of amyloidosis have been reported thus far. 2 Deposition of wild-type (wt) TTR (ATTRwt) leads to senile, non-hereditary amyloidosis, 1 with the onset typically >50 years of age. One of the >30 proteins degenerating to amyloid is transthyretin (TTR).…”

Section: Introductionmentioning

confidence: 99%

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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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