Men with cardiac amyloidosis have worse survival (76.1% vs 39.2%) in severe disease cluster, while women have higher mortality in mid-life clusters despite milder cardiac features.
Do clinical presentation, disease progression, and prognosis of cardiac amyloidosis differ between men and women?
Cardiac amyloidosis exhibits distinct sex-specific phenotypes, with men showing more severe cardiac involvement and worse survival in advanced disease, while women experience higher mortality in mid-life despite milder cardiac features.
Absolute Event Rate: 0% vs 0%
Abstract Background Cardiac amyloidosis (CA) presents with heterogeneous clinical phenotypes influenced by sex-specific differences in amyloidosis subtype prevalence, symptom progression, and cardiac remodeling. This study employs clustering analysis to explore sex-related variations in disease presentation, progression, and prognosis. Methods A cohort of 2,233 patients (1,659 men, 574 women) was analyzed, excluding those with 6 months of follow-up. Clustering analysis, using self-organizing maps (SOMs), was conducted separately for men, women, and the overall population. Clusters were defined based on age, amyloidosis subtype, cardiac/extracardiac involvement, and survival outcomes. Results Men and women were categorized into six clusters each. AL amyloidosis was more prevalent in women, particularly in clusters with systemic involvement (E, F), while ATTRwt dominated in men (A, B, C). ATTRv was more common in men, though present in women at 50%. Men exhibited higher comorbidities (hypertension, diabetes) and more severe cardiac involvement. Some clusters showed strong similarities across sexes, such as Cluster A (older patients, high ATTRwt prevalence, comparable mortality ~23%) and Cluster F (younger patients, lower ATTRwt, AL dominance in women, similar mortality ~25.8%). Others had marked sex-based differences, such as Cluster E (higher AL prevalence and systemic involvement in women, worse comorbidities and ATTRv in men, with higher male mortality) and Cluster D (most severe phenotype, with men experiencing significantly worse survival 76.1% than women 39.2%). After 5 years, 42.5% of patients had died or undergone heart transplantation, with no overall survival difference between sexes. However, survival patterns varied by cluster: men had worse survival in advanced disease (Cluster D), while women had higher mortality in mid-life clusters despite milder cardiac involvement. Conclusion Clustering analysis highlights distinct sex-specific phenotypes in CA. Men exhibit more severe cardiac involvement and worse survival in advanced disease, whereas women have higher mortality despite milder cardiac features in mid-life clusters. These findings emphasize the need for personalized, gender-specific risk stratification and treatment strategies in amyloidosis.
Zaroui et al. (Sat,) reported a other. Men with cardiac amyloidosis have worse survival (76.1% vs 39.2%) in severe disease cluster, while women have higher mortality in mid-life clusters despite milder cardiac features.