Discussion
In our study, we found that patients with a genetic diagnosis (MFS, LDS,
TS) were started on medications at lower severity of AoD at the SoV
compared to patients without a genetic diagnosis. Patients with BAV were
started on medication at a larger AAo diameter compared to patients with
genetic diagnoses and isolated AoD. Additionally, over a third (40%) of
patients in our study had family members with AoD, aortic dissection, or
vascular aneurysm. Only two patients with genetic diagnoses (1 TS, 1
MFS) had documentation of family members with aortic aneurysms during
the study period. Our cohort represents a limited number of patients
with both echocardiography and advanced imaging. From this data, there
were similar findings across each modality with good correlation
coefficients and reasonable 95% limits of agreement on the B-A plot
analyses. There were no patients identified with aortic dissection in
our study population.
The incidence of isolated AoD in the pediatric population is low and
those patients requiring intervention, whether medically or surgically,
is dependent on the aortic diameter, progression of AoD, associated
genetic conditions, and family history [15]. Aortic dissection in
children and young adults is even rarer [16, 17]. Even among
patients with CTDs, aortic dissection is rare in the pediatric
population. However, progressive AoD can occur at any period in time,
even outside the years of normal growth in children and adolescence. In
the study by Wozniak‑Mielczarek et al., they compared children and
adults with MFS and they found that the largest aortic diameters were
identified between ages 18 and 29 years [18]. Monitoring patients
with AoD becomes crucial to ensure appropriate management and education
regarding modification of cardiovascular risk factors, including
hypertension and smoking.
In a recent study by Bon et al. investigating screening for aortic
pathology in patients ≥ 15 years of age, a large percentage of patients
(60%) had a family history of thoracic aortic pathology. They also
found that close to 20% had a suspicion of a syndrome associated with
aortic pathology [7]. This also raises the topic of which patients
should be screened and once AoD is identified how should each patient be
followed and managed. Even in MFS, there has been limited data looking
at patients who develop rapid AoD. In recent literature evaluating
patients who met Ghent criteria for MFS, there were no prolific findings
that would predict rapid aortic root dilation that could be used to
indicate which patients would need referral for aortic surgery [19].
This information further emphasizes the importance of obtaining an
extended family history in patients with a diagnosis of AoD.
Based on clinical documentation and excluding genetic syndromes, factors
that influenced the decision to initiate medication in our cohort
included family history, concern for CTD, or progression of AoD. Risk
factors (smoking and hypertension) were limited in our cohort and no
patients in our analysis experienced aortic dissection. Close to
two-thirds of patients in our study had genetic testing performed if
there was concern for a genetic anomaly or CTD. It is well known that
several genes associated with aortopathy exists and have significant
familial inheritance [20–23]. Interestingly, we identified several
patients with genetic results of unknown clinical significance in our
study. Patel et al. in an abstract yielded similar findings and showed
that 10 out of 25 patients with aortic root dilation and phenotypic
findings in their study had mutations of unknown clinical significance
[24]. Although rare, some patients are diagnosed with aortic
dissection at relatively small aortic dimensions especially in very
specific conditions such as Ehlers-Danlos syndrome [25]. In these
patients it is imperative to manage them conservatively and maintain a
low index of suspicion for aortic dissection. Clinicians must be mindful
that aortopathy is a dynamic process, where aortic tissue is
structurally weakened and the association between AoD and cystic medial
necrosis/degeneration has been demonstrated [26]. Additionally, even
if some patients with AoD do not meet clinical criteria or have a
genetic diagnosis consistent with CTD, they may fall in the category of
familial aortic aneurysm syndrome [27].
Due to the variety of etiologies and presentations of pediatric patients
with AoD, there has been literature detailing algorithms and proposed
strategies for evaluating patients with AoD [11]. Echocardiography
serves as a cost-effective first line screening for AoD in suspected
individuals. In some conditions, such as TS and EDS, MRI has been the
imaging modality of choice especially when evaluating other
cardiovascular abnormalities [28]. Several studies have compared
aortic dimensions obtained by echocardiography and advanced imaging in
TS and reasonable agreement between echocardiographic and MRI
measurements has been shown. Literature also shows overestimation of
aortic dimensions at the aortic root and underestimation at the level of
the ascending aorta by echocardiography [28, 29]. When examining
patients with BAV, the pattern of aortic valve cusps fusion will
determine the geometry of AoD [30], which could influence the
diameter reported depending on the angle and level of interrogation by
echocardiogram. Advanced imaging does address the issues of angle and
level of interrogation by utilizing bi-orthogonal measurements.
Unfortunately, the factors of patient cooperation, exposure to
radiation, and sedation does determine which type of advanced imaging
modality is used (CT or MR). Shorter scanning protocols and reduction of
ionizing radiation exposure has made advanced imaging a more feasible
modality for evaluating younger patients, especially when considering
candidacy for surgery.
Surgical intervention is performed for patients that have progressive
AoD despite appropriate medical management or who meet published
recommendations for intervention due to an increased risk of aortic
dissection. There was a relatively small percentage of patients who met
inclusion criteria and underwent surgical intervention in our study. In
a study by Ono et al. the authors reported the indications for surgery
were maximal diameter of 200% of normal for isolated aneurysms, and
160% of normal in case of associated aortic valve dysfunction or
patients who were symptomatic [15]. In a recent study of MFS
patients age 6 months-25 years of age, a change in aortic root Z-score
of 0.72 SD units/year had 42% sensitivity and 92% specificity for
predicting referral for aortic surgery. The same study demonstrated that
a change in aortic root diameter of 0.34 cm/year had 38% sensitivity
and 95% specificity for predicting referral for aortic surgery, however
no new predictors of rapid AoD or referral to surgery were found
[19]. This data emphasizes that surgery should be employed for those
at highest risk for aortic dissection based on risk factors, clinical
diagnosis, and family history.