Prevalence and Outcomes of p.Val142Ile TTR Amyloidosis Cardiomyopathy: A Systematic Review

Abstract

Background: The p.Val142Ile variant, predominantly found among people of African descent, is the most common cause of variant transthyretin amyloidosis and carriers predominantly develop a cardiomyopathy (variant transthyretin amyloidosis cardiomyopathy) phenotype. Yet, there are conflicting data on the prevalence and outcomes of p.Val142Ile variant carriers.

Methods: We performed a systematic review of the prevalence and outcomes of p.Val142Ile variant transthyretin amyloidosis cardiomyopathy among subjects of African descent. We found 62 relevant articles after searching the MEDLINE databases from 1980 to 2020 that reported data for ≈150 000 subjects.

Results: The reported worldwide prevalence of the p.Val142Ile variant is 0.3% to 1.6% in the general population. Among people of African descent, the reported prevalence from all studies ranges from 1.1% to 9.8%, but for studies with >1000 subjects, it is 3% to 3.5%. The prevalence of the p.Val142Ile variant in a region is dependent on the reported percentage of subjects who are of African descent in that region. p.Val142Ile variant transthyretin amyloidosis cardiomyopathy typically presents in the seventh to eighth decade of life and the majority of cases reported were male, with 25% to 38% diagnosed with atrial fibrillation. It was associated with a longitudinally worse quality of life and a lower adjusted survival compared with other types of transthyretin amyloidosis cardiomyopathy.

Conclusions: The p.Val142Ile variant is the most common variant of the transthyretin gene with most carriers being of African descent. The true penetrance is unknown but the p.Val142Ile variant is associated with increased rates of incident heart failure and portends a lower overall survival. Increased awareness could lead to earlier diagnosis and improved heart failure outcomes among those of African descent, which is of increasing importance given the advent of novel therapeutics for this disease.

Keywords: amyloidosis; cardiomyopathies; heart failure; prevalence; transthyretin.

Figure 1.

Geographical Distribution of p.Val142Ile Variant Prevalence. World map that shows prevalence of p.Val142Ile among subjects of African descent is highest in West Africa, with next highest in USA, UK, and the Caribbean. Dark blue arrows represent 16^th century Atlantic slave trade routes providing an explanation for higher rates of p.Val142Ile in these countries. || Expanded map of USA and UK showing prevalence of p.Val142Ile variant from reported studies among those of African descent and among vATTR-CM. || Inset blue box: Prevalence of p.Val142Ile variant among those of African descent is 3% – 3.5% when restricted to studies with at least 1000 subjects. When all studies are considered, the prevalence ranges from 1.1% – 9.8%. | Prevalence of p.Val142Ile variant among vATTR-CM is 66% – 79% in the USA and UK. The prevalence ranges from 0% – 22% among studies outside of the USA and UK. | Demographics of p.Val142Ile vATTR-CM have been summarized, full details are available in Table 4. (Created with BioRender.com)

Figure 2.

PRISMA flow diagram for search strategy and results.