Acute aortic dissection (aAD) is a life-threatening condition, associated with increased
morbidity and mortality. The incidence of aAD has been estimated to occur at a rate of
6-7 cases per 100.000 persons per year and is associated with high mortality. With the
increasing availability of computed tomography scan (CT) in emergency settings, the
diagnosis of aAD was increasing in past decades, increasing up to 17 cases per 100.000
persons per year. Acute aortic event is associated with a high mortality rate ranging
from 26% in surgically treated patients to 58% in medically treated patients.
Thoracic aortic aneurysm (TAA) is a well-established risk factor for aAD but it is not a
prerequisite. Recent evidence suggests that almost 90% of aAD's occur mostly in younger
patients with aortic dimensions of <5.5 cm and only 5% of patients with diagnosed TAA are
symptomatic prior to dissection or rupture.
The majority of aAD patients are misdiagnosed, which puts them at a higher risk of death.
Timely diagnosis and surgical management of patients with TAA prior to aAD reduces the
risk of complications and death. Therefore, there is an unmet need for better and more
refined risk prediction tools to identify high-risk patients with TAA, who may benefit
from early screening and tuned surgical intervention.
Previous studies found that more than 20% of patients with TAA report a positive family
history, and the genetics of thoracic aortic aneurysm and dissection has been extensively
investigated as a potential tool for both diagnosis and risk stratification.
Traditionally, TAA is divided into syndromic-with other organ system abnormalities other
than the aorta-and non-syndromic-with no systemic abnormalities present. Several
monogenic causes for syndromic TAA are well described, such as Marfan syndrome (MFS),
Loeys-Dietz syndrome (LDS), and Ehlers-Danlos syndrome (EDS). However, the non-syndromic
TAA and aAD are more prevalent, and identifying these patients can be challenging. Some
evidence exist that mutations of genes observed in syndromic patients may be involved in
TAA and aAD in non-syndromic patients. The fact that approximately 20% of non-syndromic
TAA patients have at least one affected family member indicates that TAA could be a
heritable disease and there might be a genetic link in non-syndromic patients.
Given the inherent challenges in the diagnosis of the TAA as a precursor of aAD in
non-syndromic patients, there is a clinical need for the development of an accurate risk
prediction tools. To address the mentioned clinically relevant question, in an
observational cohort study of patients with aortic disease a molecular genetic
investigation will be conducted to investigate the genetic architecture of TAA and
individuals at high risk for aAD, and to use this information to propose patient specific
risk assessment and individually tailored management and therapy. This data will be
coupled to the routinely collected standard clinical and imaging data including computed
tomography angiography (CTA), perioperative transesophageal echocardiogram (TEE) and
transthoracic echocardiogram (TTE) with the aim to further refine risk stratification in
aAD/TAA patients.