By Michael H. Crawford, MD, Editor
SYNOPSIS: A large retrospective study from the Yale University Aortic Institute database of unoperated patients with ascending thoracic aneurysms has shown that the risk of an adverse aortic event rises significantly at 5.0 cm to 5.4 cm in maximum diameter and supports moving the guideline for surgical intervention from 5.5 cm to 5.0 cm.
SOURCE: Wu J, Zafar MA, Liu Y, et al. Fate of the unoperated ascending thoracic aortic aneurysm: Three-decade experience from the Aortic Institute at Yale University. Eur Heart J 2023;44:4579-4588.
The natural history of ascending thoracic aortic aneurysms (ATAA) is unclear because most longitudinal studies censor patients who undergo surgery rather than excluding them. Thus, the group at the Yale University Aortic Institute, headed by Dr. John Elefteriades, conducted a retrospective study of their database of adult patients with ATAA and aortic diameter ≥ 3.5 cm who did not have surgery. Excluded were those with penetrating aortic ulcers or intramural hematoma at their first visit and those with congenital malformations of the aorta. Ascending aortic size was the maximum diameter by any appropriate imaging technique at any portion of the ascending aorta.
The primary endpoint was an adverse aortic event (AAE), such as dissection, rupture, and aortic death. The study population was 964 patients: 68% were men, median age was 66 years, 9% had a bicuspid aortic valve, about 3% had a connective tissue disease, about one-half had hypertension, and about 60% smoked. They were followed for a median of 7.9 years (maximum 34 years). The aortic diameter ascribed to any AAE was the most recent measurement. Aortic diameters were grouped by 0.5-cm increments, and the ratio of aortic diameter to patient height also was assessed.
The average yearly risk of an AAE with diameters between 3.5 cm to 4.9 cm was 0.2% to 0.3% and jumped to 1.4% at 5.0 cm to 5.4 cm, 2.0% at 5.5 cm to 5.9 cm, and 3.5% at ≥ 6.0 cm. Also, 10-year survival was ≥ 97% at diameters up to 4.9 cm, then dropped to 85% at 5.0 cm to 5.4 cm, 80% at 5.5 cm to 5.9 cm, and 71% at ≥ 6 cm. The mean annual growth rate of ATAA was 0.1 cm/year and rarely exceeded 0.2 cm/year. Multivariate analysis showed that aortic size (hazard ratio [HR] = 1.78; 95% confidence interval [CI], 1.50-2.11; P < 0.001) and age (HR = 1.02; 95% CI, 1.00-1.05; P = 0.015) were independent risk factors for AAE. Of interest, hyperlipidemia was a significant protective factor (HR, 0.46; 95% CI, 0.23-0.91; P = 0.025). The authors concluded that an aortic diameter of 5.0 cm rather than 5.5 cm could be a more appropriate criterion for intervening on ATAA and, in general, the aortic growth rate is not clinically useful.
COMMENTARY
Current guidelines state that 5.5 cm should be the criterion for considering intervening on an ATAA, and some suggest 5.0 cm for those with Marfan syndrome. The studies that supported these recommendations censored patients who underwent aortic surgery instead of eliminating them; thus, they are not true natural histories. The study from Yale eliminates this bias and is large for this type of study. The authors believe that it provides enough data to support a change in guidelines to consider intervention at 5.0 cm. At this time, the standard method of correcting ATAA is surgery, since endovascular techniques for the ascending aorta still are in the experimental stage. Any decision to undergo aortic surgery should be based upon the individual’s risk of an AAE being higher than their risk of surgery. However, it is useful to have a set point where this discussion should be undertaken.
Interestingly, a bicuspid valve did not turn out to be a risk factor for an AAE in the Yale study, which supports prior studies that suggest the surgical criterion for bicuspid valve patients should be the same as for the majority of ATAA patients. The Yale study does not address the issue of Marfan patients, since few of the study’s patients fell into this category. The Yale study does support the belief that ATAA likely is genetic in origin, since common risk factors for atherosclerosis were not more prevalent in their patients and, in fact, hyperlipidemia appeared to be protective. Thus, patients with a family history of AAE perhaps should be included in those who are considered for surgery at 5.0 cm. Although aortic growth has been suggested as a criterion for surgery, it was not predictive in the Yale study, probably because it was extremely slow and rarely exceeded 0.2 cm per year.
There were limitations to this study that should be considered. This was a one-center study at an aortic disease institute where care likely was intensive. Also, it was observational and not a randomized trial. In addition, women were underrepresented, yet most studies have shown that the incidence of ATAA is the same in both sexes. However, average aortic size is smaller in women than in men. For this reason, some have suggested using the ratio of aortic size to height as a better indicator of true size. The Yale group did this analysis and reported it in the supplement to the paper. In general, it showed that an aortic size to height ratio greater than 2.2 indicated an AAE risk of > 1% per year.
Finally, the association with age and AAE is axiomatic, since the natural reluctance to be aggressive with older patients makes them overrepresented in their database. These concerns aside, the Yale study is persuasive and likely will stimulate a change in the guidelines for when to consider surgery in patients with ATAA.
