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.