Abstract
<h3>Introduction</h3> Transthyretin amyloidosis (ATTR amyloidosis) is a rare but life-threatening disease that may arise from mutations in the transthyretin (<i>TTR</i>) gene (ATTRv amyloidosis) or from nonmutated, wild-type TTR (ATTRwt amyloidosis). Evidence suggests that female sex may be protective against cardiac involvement in ATTRv amyloidosis, but sex differences in cardiac involvement in ATTRwt amyloidosis have not been assessed. <h3>Hypothesis</h3> Cardiac involvement in patients with ATTRwt amyloidosis differs by sex. <h3>Methods</h3> The Transthyretin Amyloidosis Outcomes Survey (THAOS) is a global, longitudinal, observational survey of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic patients with <i>TTR</i> mutations (NCT00628745). Data from THAOS (data cutoff: January 4, 2021) were analyzed to evaluate sex-based differences in cardiac symptoms in patients with ATTRwt amyloidosis. <h3>Results</h3> There were 1272 patients (females, n=76; males, n=1196) with ATTRwt amyloidosis enrolled in THAOS. Median age at enrollment (80.7 vs 77.6 years; <i>P</i><0.05) and symptom onset (75.5 vs 73.0 years; <i>P</i><0.05) were higher in females vs males, whereas median time from symptom onset to diagnosis was similar between the groups (1.09 vs 1.55 years). Females had a significantly higher mean left ventricular (LV) ejection fraction (53% vs 48%; <i>P</i><0.05). The lower mean LV wall thickness (16 vs 17 mm) and mean LV mass index (161 vs 189 g/m<sup>2</sup>) observed in females vs males were not statistically significant. LV wall thickness (mm) divided by height (m) was similar in females vs males (9.8 vs 9.6). Sex was not found to be a predictor of mean LV wall thickness divided by height in a linear regression analysis. <h3>Conclusions</h3> Females with ATTRwt amyloidosis were older and had a higher mean LV ejection fraction compared with males. Although there were signs of sex-related differences in cardiac involvement, the relatively low number of females in this analysis may have limited the ability to draw firmer conclusions.
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