Race, Genotype, and Prognosis in Black Patients With Transthyretin Cardiac Amyloidosis

Abstract

Previous studies suggest worse outcomes in patients with variant transthyretin cardiac amyloidosis due to V122I (ATTRv-CA) compared to patients with wild-type disease (ATTRwt-CA). Given V122I is almost exclusively found in Black patients, it is unclear if this is attributable to the biology of genotype or racial differences. Patients with transthyretin cardiac amyloidosis (ATTR-CA) diagnosed between January 2001 and August 2021 were characterized into 3 categories: (1) White with ATTRwt-CA (White- WT); (2) Black with V122I ATTRv-CA (Black-V122I), and (3) Black with ATTRwt-CA (Black-WT). Event-free survival (composite of death, left ventricular assist device (LVAD), or cardiac transplant) was evaluated using univariable and multivariable analyses over a median follow-up of 1.6 (0.7-2.90) years. Of 694 ATTR-CA patients, 502 (72%) were White-WT, 139 (20%) Black-V122I, and 53 (8%) Black- WT. Notably, 28% of Black patients with ATTR-CA had wild-type disease and not the V122I variant. Using multivariable modeling to adjust for several prognostic features, Black-V122I had higher risk of the composite adverse outcome compared with a grouped cohort of patients with WT disease (White-WT and Black-WT) [hazard ratio (HR) 1.82, CI 1.30-2.56, p<0.001). Furthermore, the Black cohort as a whole (Black- V122I and Black-WT) demonstrated greater risk of adverse outcomes compared to White-WT (HR 1.63, CI 1.19-2.24, p=0.002). Black-V122I had greater risk of the primary endpoint compared to White-WT (HR 1.80, CI 1.27-2.56, p=0.001). Black patients with ATTR-CA have worse event-free survival than White-WT despite risk adjustment. However, it remains unclear whether this is driven by differences in race or genotype given the smaller number of Black-WT patients. Approximately one-quarter of Black patients had WT, of which a greater proportion were female compared to White-WT.