Expert Consensus Recommendations for the Suspicion and Diagnosis of Transthyretin Cardiac Amyloidosis

To propose a correlation between polyneuropathy and ATTRwt based on retrospective analysis of patients with ATTRwt. We reviewed 151 ATTRwt patients followed by the amyloid cardiac clinic (group A) for symptoms of neuropathy and 12 patients with ATTRwt evaluated in the Neurology Department (group B) with objective measures of neuropathy. Medical history, electrodiagnosis, laboratory and skin biopsies were assessed; 30.5% of group A had neuropathy symptoms. Alternative explanations for neuropathy symptoms were explored, including, age, gender, BMI, diabetes mellitus, B12 deficiency. No difference was observed for BMI, age, gender and spine disease for those with and without neuropathic symptoms (P > .05). All of group B (n = 12) were diagnosed with neuropathy, confirmed by electrodiagnostic testing or skin biopsy, while two patients had not yet developed cardiac symptoms. We observe a higher prevalence of neuropathic symptoms in ATTRwt patients than previously believed. Neuropathic symptoms may precede cardiac symptoms. Our findings suggest a possible causative relationship that requires further investigation.

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“…No informed consent was required. All patients had confirmed diagnosis of ATTRwt based on AHA cardiac transthyretin amyloidosis consensus 2,7,8 …”

Section: Methodsmentioning

confidence: 99%

Peripheral neuropathy symptoms in wild type transthyretin amyloidosis

Yungher

Kim

Boehme

et al. 2020

J Peripheral Nervous Sys

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“…In clinical practice, it is critical to distinguish between treatable versus non-treatable amyloidoses. Moreover, amyloidoses with a genetic component must be distinguished from the sporadic types and systemic amyloidoses must be distinguished from the localized forms [5][6][7][8][9][10][11][12]. AL, amyloidosis derived from immunoglobulin light chain, has been considered, thus far, the most common form of systemic amyloidosis in the developed world [6,7,12,13].…”

Section: Classificationmentioning

confidence: 99%

“…Hereditary amyloidosis caused by mutations in the TTR gene (TTRv, variant) has begun to emerge as a significantly underdiagnosed cause of cardiac failure and polyneuropathy [8][9][10]12]. The worldwide prevalence of ATTRv is estimated at 50,000 individuals, with varying phenotypic presentations [29].…”

Section: Hereditary Amyloidosesmentioning

confidence: 99%

The Pathology of Amyloidosis in Classification: A Review

2020

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Background: The amyloidoses are a rare and heterogeneous group of disorders that are characterized by the deposition of abnormally folded proteins in tissues ultimately leading to organ damage. The deposits are mainly extracellular and are recognizable by their affinity for Congo red and their yellow-green birefringence under polarized light. Current classification of amyloid in medical practice is based on the amyloid protein type. To date, 36 proteins have been identified as being amyloidogenic in humans. Summary: in clinical practice, it is critical to distinguish between treatable versus non-treatable amyloidoses. Moreover, amyloidoses with a genetic component must be distinguished from the sporadic types and systemic amyloidoses must be distinguished from the localized forms. Among the systemic amyloidoses, AL continues to be the most common amyloid diagnosis in the developed world; other clinically significant types include AA, ALECT2, and ATTR. The latter is emerging as an underdiagnosed type in both the hereditary and wild-type setting. Other hereditary amyloidoses include AFib, several amyloidoses derived from apolipoproteins, AGel, ALys, etc. In a dialysis setting, systemic amyloid derived from β 2 microglobulin (Aβ2M) should be considered, although a very rare hereditary variant has also been reported; several amyloido-ses may be typically associated with aging and several iatrogenic types have also emerged. Determination of the amyloid protein type is imperative before specific therapy can be implemented and the current methods are briefly summarized. A brief overview of the target organ involvement by amyloid type is also included. Key Messages: (1) Early diagnosis of amyloidosis continues to pose a significant challenge and requires the participation of many clinical and laboratory specialties. (2) Determination of the protein type is imperative before specific therapy can be implemented. (3) While mass spectrometry has emerged as the preferred method of amyloid typing, careful application of immune methods is still clinically useful but caution and experience, as well as awareness of the limitations of each method, are necessary in their interpretation. (4) While the spectrum of amyloidoses continues to expand, it is critical to distinguish between those that are currently treatable versus those that are untreatable and avoid causing harm by inappropriate treatment.

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“…Transthyretin protein misfolds to form ibrils that deposit in various tissues and organs. In addition to being debilitating, this disease is associated with a poor life expectancy, especially in those with cardiac dysfunction, however, the recent appearance of a wide range of effective therapeutic possibilities, allow early diagnosis and treatment is essential, since, the effectiveness of the treatment increases in the early stages of this disease [4].…”

Section: Discussionmentioning

confidence: 99%