Women exhibit a more favorable phenotype and prognosis than men in cardiac transthyretin amyloidosis
M El Blidi, V Quentin, S Badini-Kontogom, C Statescu, E Berthelot, F BauerAbstract
Background
Cardiac amyloidosis has emerged as a major and increasingly recognized cause of heart failure. Although sex-related differences in disease prevalence have been reported, the influence of sex on cardiac phenotype and clinical outcomes—particularly in transthyretin amyloidosis (ATTR)—remains incompletely defined.
Methods
We performed a retrospective observational study including 338 patients with a confirmed diagnosis of cardiac ATTR amyloidosis. Patients were stratified according to sex. Continuous clinical, biological, and echocardiographic variables were compared using independent two-sample t-tests. Overall survival was assessed using Kaplan–Meier estimates, with between-group comparisons performed using the log-rank test. Follow-up was truncated at 2500 days to minimize the impact of sparse late events. Statistical significance was defined as a two-sided p-value < 0.05.
Results
Men accounted for 74% of the cohort, whereas women represented 26%. Age at diagnosis was similar between sexes (80.2 ± 10.1 years in men vs 80.1 ± 9.4 years in women, p = 0.35). Left ventricular systolic function did not differ significantly, with comparable LVEF values in men and women (53.9 ± 19% vs 54.7 ± 19%, p = 0.63). In contrast, men exhibited significantly greater left ventricular hypertrophy, with increased interventricular septal thickness (16.2 ± 3.7 mm vs 14.4 ± 3.9 mm, p = 0.008) and posterior wall thickness (15.4 ± 4.2 mm vs 14.1 ± 4.0 mm, p = 0.02). Right ventricular cavity dimensions were also larger in men. Despite similar disease severity at presentation, as reflected by comparable NYHA functional class (p = 0.28) and NT-proBNP levels (p = 0.96), Kaplan–Meier survival analysis demonstrated higher unadjusted survival in women throughout follow-up (logrank = 0,02, figure).
Conclusion
Sex-related differences in cardiac ATTR amyloidosis are primarily structural rather than functional, with men demonstrating more advanced myocardial hypertrophy. Women exhibit a more favorable cardiac phenotype and a trend toward improved survival. These findings underscore the relevance of sex-specific considerations in the phenotypic assessment and prognostic evaluation of cardiac ATTR amyloidosis.Kaplan-Meier survival curve by sexFor image description, please refer to the figure legend and surrounding text.