Page 189 - Read Online

Page 4 of 15 Levy et al. Vessel Plus 2024;8:4 https://dx.doi.org/10.20517/2574-1209.2023.55

exposure was significantly decreased in FDR compared to those without a family history (18.3 vs. 43.1
[16]
years) . We recently demonstrated a significant increase in cumulative lifelong aortic mortality in close
[17]
relatives of patients with thoracic aortic disease using the Utah Population database .
It is likely that this increased mortality risk is related to more aggressive rates of growth and aneurysm
progression in the setting of ns-TAAD patients. Coady and Albornoz found an increased growth rate of
aneurysms in the familial cases compared to sporadic and MFS: 0.21-0.22 cm/year vs. 0.03-0.16 cm/year and
0.10 cm/year, respectively [9,14] . Albornoz also found that familial aortopathy patients tended to be younger at
the time of diagnosis compared to those with sporadic aneurysms. In Ma’s pedigree analysis of 51 sporadic
dissections and 39 familial dissections, over half of the familial dissections presented within 10 years of the
age at which their respective family member experienced dissection and an overall younger age than
sporadic cases. Altogether, this data suggests an important role for screening in ns-TAAD that may inform
earlier timing of prophylactic elective thoracic aortic aneurysm surgery to prevent dissection in younger
patients with positive family history, especially if they are within 10 years of the age of onset in an affected
relative .
[18]
Observational studies
Several observational and database studies have focused on elucidating risk factors, incidence, and outcomes
of TAAD. The International Registry of Acute Aortic Dissection (IRAD) was established in 1996 to collect
data on demographics, history of present illness, physical exam, imaging, management, and outcomes
across over 50 centers worldwide to better understand acute aortic pathology. Januzzi et al. reviewed IRAD
data of 951 patients with aortic dissection to investigate risk factors and mortality. Patients aged 40 years
and younger were found to have larger aortic diameters and less likely to have hypertension. Of these
younger patients, 69% had either MFS or prior aortic valvulopathy, but 31% of patients had no known
genetic etiology or aortic valvular disease. Mortality rates were unexpectedly similar between the older and
[19]
younger groups and were noted not to be due to a delay in diagnosis . In 2018, Evangelista et al. reported
on the IRAD 20-year experience, noting that 60% of patients presenting with acute aortic dissection had
maximum aortic diameters less than 5.5 cm - the guideline-recommended diameter for elective thoracic
aortic aneurysm repair - and 40% actually had a diameter less than 5 cm - a cohort that included more
[20]
patients with MFS and BAV .

In a Swedish population-based study of over 14,000 patients, the incidence of thoracic aortic disease was
found to be increasing compared to previous reviews, which was attributed to improved diagnostic testing.
They also found that perioperative and long-term survival rates have improved, suggesting that many cases
go undiagnosed and improved screening guidelines will highly likely improve outcomes .
[21]
In a prospective registry study of 270 newly diagnosed ns-TAAD cases under the age of 60, 43% presented as
acute aortic dissection. After screening relatives of these newly diagnosed probands, 216 new diagnoses were
made, with 181 of these diagnoses found in FDRs. Of the 216 newly diagnosed relatives, 86 relatives were
diagnosed through a sporadic proband, which transitioned these “sporadic” pedigrees to a familial
aortopathy pedigree. In further support outlining the extent of phenotypic variability, six individuals who
were initially clinically proven to be unaffected by an aortopathy went on to experience aortic dissection
during the follow-up period. One in six patients under the age of 60 presenting with thoracic aortopathy
met the author’s diagnostic criteria for ns-TAAD . This highlights the increased incidence of heritable
[22]
TAAD and thus a need for more defined screening and management guidelines for ns-TAAD.