Wild-type transthyretin cardiac amyloidosis: sex differences in prevalence, phenotype, and prognosis

Background To explore sex differences in the course and phenotype of wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) and determine sex- and age-related survival and prognostic factors. Methods In a retrospective cohort study conducted at the French Cardiac Amyloidosis Reference Center from January 1st, 2008, to December 31st, 2022, we used multiple regression analyses, supervised clustering, Cox models, and a Kaplan-Meier analysis to compare the characteristics of women and men in age quartiles (Qs). Results We included 1062 patients with ATTRwt-CM (180 women, 16%). The women had a higher median [interquartile range] left ventricular ejection fraction (LVEF; 52% [45-60] vs. 50 [43-58] in men) and a lower interventricular septum thickness. 12% of the women and 4.1% of the men had a septum thickness <12 mm (p=.004). The women in Q1 (age at diagnosis ≤77y) 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 older women and men. The death rate for women was higher in Q1 than in Q2-4. 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=.001). Tafamidis treatment was associated with better survival in men (hazard ratio [95% confidence interval] = 0.61 [0.39-0.95]) but not in women. Conclusions Younger women (≤77y) with ATTRwt-CM had a thin left ventricle wall but a high death rate. Decreasing the septum thickness cut-off would increase the frequency of ATTR-CM diagnosis in women.