Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness

Damy, Thibaud; Costes, Bruno; Hagège, Albert; Donal, Erwan; Eicher, Jean‐Christophe; Slama, Michel; Guellich, Aziz; Rappeneau, Stéphane; Gueffet, Jean-Pierre; Logeart, Damien; Planté‐Bordeneuve, Violaine; Bouvaist, Hélène; Huttin, Olivier; Mulak, Geneviève; Dubois‐Randé, Jean‐Luc; Goossens, M; Canouï‐Poitrine, Florence; Buxbaum, Joel N.

doi:10.1093/eurheartj/ehv583

Cited by 185 publications

(138 citation statements)

References 24 publications

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“…26 Moreover, the Beta-Blocker Evaluation of Survival Trial study showed a high prevalence of the Val122Ile variant in elderly African Americans with severe HF. In a prospective multicentre study in France, genetic screening for a TTR gene revealed that 5% of 298 consecutive elderly patients (>60 years old) clinically diagnosed with HCM have ATTRv-CA with a predominance of the Val122Ile variant.…”

Section: Implications Of Genetic Diagnosis Of Transthyretin Gene Sequmentioning

confidence: 99%

Transthyretin cardiac amyloidosis: an update on diagnosis and treatment

Yamamoto¹,

2019

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Transthyretin cardiac amyloidosis (ATTR-CA) demonstrates progressive, potentially fatal, and infiltrative cardiomyopathy caused by extracellular deposition of transthyretin-derived insoluble amyloid fibrils in the myocardium. Two distinct types of transthyretin (wild type or variant) become unstable, and misfolding forms aggregate, resulting in amyloid fibrils. ATTR-CA, which has previously been underrecognized and considered to be rare, has been increasingly recognized as a cause of heart failure with preserved ejection fraction among elderly persons. With the advanced technology, the diagnostic tools have been improving for cardiac amyloidosis. Recently, the efficacy of several disease-modifying agents focusing on the amyloidogenic process has been demonstrated. ATTR-CA has been changing from incurable to treatable. Nevertheless, there are still no prognostic improvements due to diagnostic delay or misdiagnosis because of phenotypic heterogeneity and comorbidities. Thus, it is crucial for clinicians to be aware of this clinical entity for early diagnosis and proper treatment. In this mini-review, we focus on recent advances in diagnosis and treatment of ATTR-CA.

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Section: Implications Of Genetic Diagnosis Of Transthyretin Gene Sequmentioning

confidence: 99%

Transthyretin cardiac amyloidosis: an update on diagnosis and treatment

Yamamoto¹,

2019

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“…Surprisingly, the most common mutation was TTR V122I. 21 The ethnic origin of the V122I-positive subjects is under investigation.…”

Section: Disease Associationsmentioning

confidence: 99%

Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans

Buxbaum

Ruberg

2017

Genetics in Medicine

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124

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Since the identification of a valine-to-isoleucine substitution at position 122 (TTR V122I; pV142I) in the transthyretin (TTR)-derived fibrils extracted from the heart of a patient with late-onset cardiac amyloidosis, it has become clear that the amyloidogenic mutation and the disease occur almost exclusively in individuals of identifiable African descent. In the United States, the amyloidogenic allele frequency is 0.0173 and is carried by 3.5% of community-dwelling African Americans. Genotyping across Africa indicates that the origin of the allele is in the West African countries that were the major source of the slave trade to North America. At autopsy, the allele was found to be associated with cardiac TTR amyloid deposition in all the carriers after age 65 years; however, the clinical penetrance varies, resulting in substantial heart disease in some carriers and few symptoms in others. The allele has been found in 10% of African Americans older than age 65 with severe congestive heart failure. At this time there are potential forms of therapy in clinical trials. The combination of a highly accurate genetic test and the potential for specific therapy demands a greater awareness of this autosomal dominant, age-dependent cardiac disease in the cardiology community.

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“…Clinical and imaging findings may be attributed to other causes of left ventricular hypertrophy and delay diagnosis, while more extensive deposition can mimic hypertrophic cardiomyopathy. 34 Atrial arrhythmias are frequent and the risk of left atrial appendage thrombosis is increased. 35,36 …”

Section: Early Diagnostic Cluesmentioning

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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Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness

Abstract: Five per cent of patients diagnosed with hypertrophic cardiomyopathy have mTTR-FAC. Mutated transthyretin genetic screening is warranted in elderly subjects with increased LVWT, particularly, those of African descent with neuropathy, carpal tunnel syndrome, ECG low voltage, or LGE.

Cited by 185 publications

References 24 publications

Transthyretin cardiac amyloidosis: an update on diagnosis and treatment

Transthyretin cardiac amyloidosis: an update on diagnosis and treatment

Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans

Transthyretin Cardiac Amyloidosis in Black Americans

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