V122I Transthyretin Variant in Elderly Black Americans

Quarta, Candida Cristina; Falk, Rodney H.; Solomon, Scott D.

doi:10.1056/nejmc1503222

Cited by 4 publications

(3 citation statements)

References 4 publications

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“…Studies evaluating senile, or wild type transthyretin (ATTRwt) almost exclusively consisted of White patients, however population based data from the United Kingdom reported an equal prevalence of ATTRwt among races. 8 Under-recognition of disease may explain why Blacks are poorly represented in American studies of senile cardiac amyloidosis. 9 …”

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confidence: 99%

Transthyretin Cardiac Amyloidosis in Black Americans

Shah

Mankad

Castaño

et al. 2016

Circ: Heart Failure

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Transthyretin (TTR) related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive, hypertrophic heart disease and often goes undiagnosed. In the United States, the hereditary form disproportionately afflicts Black Americans, who when compared to Caucasians with wild type TTR amyloidosis, a phenotypically similar condition, present with more advanced disease despite having a non-invasive method for early identification (genetic testing). While reasons for this are unclear, this begs to consider the inadequate access to care, societal factors or a biological basis. In an effort to improve awareness and explore unique characteristics, we review the pathophysiology, epidemiology and therapeutic strategies for TTR amyloidosis, and highlight diagnostic pitfalls and clinical pearls for identifying patients with amyloid heart disease.

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confidence: 99%

Transthyretin Cardiac Amyloidosis in Black Americans

Shah

Mankad

Castaño

et al. 2016

Circ: Heart Failure

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“…The prevalence of ATTR disease due to a genetic variant depends on the prevalence of specific causative pathologic TTR variants that are concentrated in regions of the world, with higher frequencies observed in areas such as County Donegal, Republic of Ireland (1% population prevalence of a pathologic TTR genetic variant) or in northern Sweden (4% population prevalence of a pathologic TTR variant) (Table 1). ATTR amyloidosis due to a genetic variant is more common in people who are older, and the association of older age with ATTR amyloidosis depends on the genetic variant. Genetic variants are inherited in an autosomal dominant manner.…”

Section: Discussionmentioning

confidence: 99%

“…This variant originated in the western coast of Africa and is associated with development of ATTR cardiomyopathy later in life, typically after age 60 . There is considerable variation in reported penetrance of Val122Ile, from 7% (based on echocardiography-demonstrated increased wall thickness) to 39% (based on nuclear scintigraphy) to 100% (autopsy specimens) . These data have led to confusion regarding the prevalence of ATTR cardiomyopathy that results from the Val122Ile variant.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Amyloidosis Due to Transthyretin Protein

Ruberg,

Maurer

2024

JAMA

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ImportanceSystemic amyloidosis from transthyretin (ATTR) protein is the most common type of amyloidosis that causes cardiomyopathy.ObservationsTransthyretin (TTR) protein transports thyroxine (thyroid hormone) and retinol (vitamin A) and is synthesized predominantly by the liver. When the TTR protein misfolds, it can form amyloid fibrils that deposit in the heart causing heart failure, heart conduction block, or arrhythmia such as atrial fibrillation. The biological processes by which amyloid fibrils form are incompletely understood but are associated with aging and, in some patients, affected by inherited variants in the TTR genetic sequence. ATTR amyloidosis results from misfolded TTR protein deposition. ATTR can occur in association with normal TTR genetic sequence (wild-type ATTR) or with abnormal TTR genetic sequence (variant ATTR). Wild-type ATTR primarily manifests as cardiomyopathy while ATTR due to a genetic variant manifests as cardiomyopathy and/or polyneuropathy. Approximately 50 000 to 150 000 people in the US have heart failure due to ATTR amyloidosis. Without treatment, heart failure due to ATTR amyloidosis is associated with a median survival of approximately 5 years. More than 130 different inherited genetic variants in TTR exist. The most common genetic variant is Val122Ile (pV142I), an allele with an origin in West African countries, that is present in 3.4% of African American individuals in the US or approximately 1.5 million persons. The diagnosis can be made using serum free light chain assay and immunofixation electrophoresis to exclude light chain amyloidosis combined with cardiac nuclear scintigraphy to detect radiotracer uptake in a pattern consistent with amyloidosis. Loop diuretics, such as furosemide, torsemide, and bumetanide, are the primary treatment for fluid overload and symptomatic relief of patients with ATTR heart failure. An ATTR-directed therapy that inhibited misfolding of the TTR protein (tafamidis, a protein stabilizer), compared with placebo, reduced mortality from 42.9% to 29.5%, reduced hospitalizations from 0.7/year to 0.48/year, and was most effective when administered early in disease course.Conclusions and RelevanceATTR amyloidosis causes cardiomyopathy in up to approximately 150 000 people in the US and tafamidis is the only currently approved therapy. Tafamidis slowed progression of ATTR amyloidosis and improved survival and prevented hospitalization, compared with placebo, in people with ATTR-associated cardiomyopathy.

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