Male-female differences in the natural history of ascending thoracic aortic aneurysms: insights from the dissexion study
Authors: Notenboom M , De Keijzer A R , Veen K M , Gokalp A , Bogers A J J C , Heijmen R H , Van Kimmenade R R J , Geuzebroek G S C , Mokhles M M , Bekkers J A , Roos-Hesselink J W , Takkenberg J J M 
Published: November 2023

Abstract

Background
The natural history of ascending thoracic aortic aneurysms (ATAAs) remains poorly understood, including potential male-female differences.

Purpose
Therefore, this study sought to evaluate the natural history and outcomes of patients with ATAAs, with an emphasis on aortic growth and male-female differences.

Methods
Adult patients who received diagnostic and/or follow-up imaging of an ATAA (≥40mm) in two academic centers between 2007-2021 were included. Aortic growth was modeled non-linearly through mixed-effects models using repeated measurements, including age and sex through interaction terms. Joint models were constructed to adjust for the effect of nonrandom dropout due to surgical intervention. Secondary outcomes were male-female differences in presentation, aneurysm characteristics, time to intervention, acute aortic syndromes and survival relative to the age- and sex-matched general Dutch population. Cox models were employed to evaluate predictors of intervention and survival.

Results
In total, 1,858 patients were included (31.6% female). Median clinical follow-up was 5.9 [IQR: 3.0-10.0] years. Median age was 65.4 years [53.4-71.7y] for females and 59.0 years [IQR: 49.3-68.0y] for males (p&lt;0.001). Males had more bicuspid aortic valve (BAV) disease (male: 27.5%, female: 18.2%; p&lt;0.001) and were more likely to have had a previous dissection or aneurysm in a major artery other than the thoracic aorta (male: 8.9%, female: 4.9%; p=0.004) before diagnosis. Maximum absolute aortic diameter at diagnosis did not differ between males (46.5mm) and females (45.0mm; p=0.388). Unadjusted 10-year survival was 76% (68%-78%) for females (relative survival: 68.8%) and 78% (75%-81%) for males (relative survival: 78.7%). For females, tubular ascending aortic growth was faster compared to males (p=0.005), particularly in the first 6 years after diagnosis. Contrarily, SoV growth was faster in males compared to females (p=0.002). Surgical intervention occurred more quickly after diagnosis in females (HR: 2.5 (1.2-5.2), corrected for BAV, diameter and age. Twenty-three type A dissections (TAD) occurred with an incidence rate ratio between females and males of 3.4 (95%CI:1.5-8.0, p=0.004). The last known aortic diameter before TAD was comparable between males (47.5mm [47.0-50.8]) and females (47.0mm [43.0-51.0]; p=0.416).

Conclusions
Ascending aortic aneurysms show a strikingly different growth pattern between males and females at the level of the SoV and tubular ascending aorta, suggesting that although females present at an older age, their aortic disease progresses faster and with more TAD compared to males, and warranting an even more careful follow-up. Absolute known aortic diameter before TAD was comparable between males and females. These insights can be used to fuel discussion about male-female specific follow-up and treatment recommendations in future clinical guidelines development.Ascending aortic growth (A) & sinus (B)Freedom from intervention from diagnosis