Men and women differ with regard to the prevalence, phenotype, and prognosis of wild-type transthyretin amyloid cardiomyopathy

Abstract

Background: We explored sex differences in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) and determined survival and prognostic factors.

Methods: In a retrospective cohort study at a reference centre in France from 1 January 2008 to 31 December 2022, multiple regression analyses, supervised clustering, Cox models, and a Kaplan-Meier analysis were used to compare women and men in each age quartile (Q1: ≤77 years; Q2: 78-82; Q3: 83-86; Q4 > 86).

Results: We included 1062 patients with ATTRwt-CM (180 women, 16%). The women had a higher median [IQR] left ventricular ejection fraction (LVEF; 52% [45-60] vs. 50 [43-58] in men) and a thinner interventricular septum. 12% of women and 4.1% of men had a septum thickness <12 mm (p = 0.004). The women in Q1 had lower LVEF and global longitudinal strain values and a higher prevalence of a septum <12 mm (15.8%, vs 2.0% in men) than men and older women (Q2-Q3-Q4). Women had a greater risk of sudden death than men (13.8% vs. 4.6%, respectively; odds ratio [95% confidence interval]: 3.24 [1.56-6.64]; p = 0.001).

Conclusions: In women, the ATTRwt-CM phenotype and prognosis are related to age at diagnosis. Decreasing the septum thickness cut-off would increase the frequency of ATTR-CM diagnosis in women.

Keywords: Transthyretin amyloid cardiomyopathy; interventricular septum thickness; prevalence; prognosis; sex differences.