Abstract 9447: The Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations Study

Abstract

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF) among patients aged > 60 years. While the V122I variant that is associated with hereditary ATTR-CM is present in 3.4% of self-identified Black individuals in the US (or 1.5 million people), the phenotypic penetrance of this allele remains incompletely defined owing to age-dependent expression and limited methods for disease ascertainment. Methods: The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study is a currently accruing multisite cohort designed to determine the prevalence of ATTR-CM using Tc-99m-Pyrophosphate imaging in older (age > 60 years) Black and Hispanic individuals with HF. TTR genotype is determined by 4-exon targeted PCR, while functional, biochemical, and echocardiographic testing is performed. Data are presented here as an interim analysis performed using Kruskal-Wallis testing for the first 240 self-identified Black participants. Results: The prevalence of V122I was 6.7% (n=16 carriers of whom 7 had ATTR-CM), yielding a phenotypic penetrance of 44% (95% CI 20%, 70%) at a median age of 82 (IQR 74, 85) years. Allele carriers with ATTR-CM (Group 3) were older and more likely male, with lower 6-minute walk distance and LVEF, when compared to carriers without ATTR-CM (Group 2, Table) or wild-type, non-amyloid HF controls (Group 1). Other functional, biochemical, and echocardiographic parameters were predictably different between Group 3 and the other groups but similar between Groups 1 and 2 except for prealbumin levels (Group 1: 25 mg/dl vs. Group 2: 20.5 mg/dl, p < 0.05). Conclusion: The clinical penetrance of V122I among elderly Black individuals with HF and a median age of 82 years was 44%, suggesting that genotype alone is insufficient to infer ATTR-CM as the cause of HF in this clinical context. Prealbumin concentration may be useful to identify ATTR-CM in V122I carriers.