Biomechanical and morphological aspects of abdominal aortic aneurysm growth and rupture

Abdominal aortic aneurysms (AAAs) are dilatations of the abdominal aorta that pose a risk of rupture. The only effective treatment is intervention prior to rupture, but this is also associated with mortality and morbidity. It is therefore important to weigh the risks of intervention with the potential benefit. Current treatment guidelines recommend using the maximal aneurysm diameter (Dmax) as the indicator for rupture risk, and recommend considering intervention in men with AAAs > 55 mm, and >50 mm in women. Patients with small AAAs are put in surveillance, and the Dmax is followed until it reaches the threshold. The current policy is relatively efficient on a population-level but lacks specificity for individuals. Some patients rupture before this threshold, and many remain stable despite passing it. Aneurysm growth is often described as erratic, but measurements are affected by several levels of uncertainty. Biomechanical assessment, where 3D models of AAAs from computed tomography angiographies (CTAs) are analysed by finite element analysis, may improve risk prediction.

In the first study a population-based cohort of 192 patients with ruptured AAAs and CT imaging available at rupture were studied. A significant portion of patients ruptured with AAAs smaller than 60 mm, 10% of men and 27 % of women. When normalizing Dmax for body surface area (so-called aortic size index) there was, however, was not difference between the sexes. In an analysis of small, ruptured AAAs compared to Dmax, age and sex-matched asymptomatic AAAs, peak wall rupture index (PWRI), but not peak wall stress (PWS) was increased in the ruptured AAAs.

In the second study, a cohort of 100 patients with at least three computed tomography examinations were analysed with 3D morphological and biomechanical analysis. The growth pattern of AAAs appeared continuous and conferred well to a linear growth model. The evolution of the different analysed indices, Dmax, aneurysm volume and bio-mechanical stress did, however, not parallel each other. Intraluminal thrombus (ILT) grew faster than the lumen, but lumen volume growth was more closely related to increase in biomechanical stress.

In the third study, a cohort of 67 patients with 109 CTA examinations prior to rupture were identified. The relation between biomechanical variables and time-to-rupture was investigated. In small and medium sized AAAs (< 70 mm), PWRI, but not PWS, was associated with time-to-rupture, also when adjusting for potential confounders, aneurysm size and sex. The results further show that women have an approximately two-fold increased hazard ratio for AAA rupture, compared to men, when adjusted for AAA size.

In the fourth study lumen area is indicated as a potentially useful rupture risk marker. Ruptured AAAs, compared to Dmax-matched asymptomatic AAAs, have a larger luminal area, and the luminal area is related to biomechanical stress, even when adjusting for aneurysm size, or ILT area.

In conclusion, the results of this thesis indicate areas of potential improvement in the current care of patients with AAAs, explores the 3D growth of AAAs, and strengthens the potential role for biomechanical analysis. These results may in the future have relevance for personalizing timing of treatment for patients with AAAs, and the evaluation of pharmacological therapy for AAAs.

List of scientific papers

I. Siika A, Lindquist Liljeqvist M, Zommorodi S, Nilsson O, Andersson P, Gasser TC, Roy J, Hultgren R. A large proportion of patients with small ruptured abdominal aortic aneurysms are women and have chronic obstructive pulmonary disease. PLoS One. 2019 May 28;14(5):e0216558.
https://doi.org/10.1371/journal.pone.0216558

II. Siika A, Bogdanovic M, Lindquist Liljeqvist M, Gasser TC, Hultgren R, Roy J. Three-dimensional Growth and Biomechanical risk Progression of Abdominal Aortic Aneurysms under Serial Computed Tomography Assessment. [Manuscript]

III. Siika A, Talvitie M, Lindquist Liljeqvist M, Bogdanovic M, Gasser TC, Hultgren R, Roy J. Peak Wall Rupture Index is Associated with Time-to-Rupture in Abdominal Aortic Aneurysms Independently of Size and Sex. [Manuscript]

IV. Siika A, Lindquist Liljeqvist M, Hultgren R, Gasser TC, Roy J. Aortic Lumen Area Is Increased in Ruptured Abdominal Aortic Aneurysms and Correlates to Biomechanical Rupture Risk. J Endovasc Ther. 2018 Dec;25(6):750-756.
https://doi.org/10.1177/1526602818808292