Key result
Pathogenic TTR V142I variant occurs in ~12% of African-American patients with HFpEF.
Why the study?
V142I ATTR-CA is often unrecognized, and it remains unknown which TTR V142I carriers will progress to heart failure and at what age.
Observational (n=26)
Yes
Absolute Event Rate: 11.5% vs 3.4%
A high prevalence (11.5%) of the pathogenic TTR V142I variant was found in a small cohort of African-American patients with HFpEF, suggesting potential utility for routine genotyping in this population.
Does not support routine TTR genotyping in African-American HFpEF; hypothesis-generating for targeted screening pending prospective validation.
Transthyretin cardiac amyloidosis (ATTR-CA) is a treatable cause of heart failure with a hereditary form that disproportionally affects patients of West African ancestry. The clinical management of ATTR-CA has dramatically changed in the past five years, with rapidly evolving diagnostic approaches and life-prolonging therapies. The TTR variant c.424G>A, p.V142I (aka V122I) is pathogenic and occurs in 3-4% of individuals of West African ancestry. Despite its high frequency, V142I ATTR-CA is often unrecognized due to variable clinical penetrance, limited knowledge, and lack of inexpensive non-invasive diagnostic tests. Currently unknown is which TTR V142I carriers will progress to heart failure and at what age. Here we studied the prevalence of TTR V142I among a random cohort of African-American patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT). Three of the 26 HFpEF patients (11.5%) studied carried the pathogenic TTR V142I variant. While we cannot conclude at this point that TTR V142I was the underlying cause of the clinical phenotype in these patients, our results suggest that rapid TTR V142I genotyping, in combination with heart imaging, could have immediate clinical utility for identifying under-/mis-diagnosed HFpEF patients.
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Papoutsidakis et al. (2020) conducted an observational in Heart failure with preserved ejection fraction (HFpEF) (n=26). Pathogenic TTR V142I variant vs. General African-American population was evaluated on Prevalence of the pathogenic TTR V142I variant. The pathogenic TTR V142I variant was found in 11.5% of African-American patients with HFpEF from the TOPCAT trial, representing an enrichment compared to the 3.4% prevalence in the general population.
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