The etiologic diagnoses in the patients analyzed in this study align with previous reports[2, 3, 10]. Notably, conditions such as TA, FMD, and Williams syndrome have been well-described in previous studies. Furthermore, the case of Patient 1, who presented with CHOPS syndrome in this study, has already been discussed in a separate case report[11]. However, a particularly unique finding in this study is the presence of familial FMD in both patients diagnosed with MAS. Patient 11, initially diagnosed with MAS and left ventricular dysfunction, shares notable similarities with their younger sister, Patient 10, who initially underwent blood pressure monitoring and later received a diagnosis of MAS. Both patients showed similar clinical manifestations in terms of the involved aortic zone, presence of RAS, and cerebral artery involvement. While genetic testing was recommended for these patients, it has not yet been conducted. In addition to the aforementioned findings, it is worth noting that Patient 5 has already been documented as a case report representing the first reported case of idiopathic MAS in childhood in Korea[12].
This study presents a significant contribution by being the first to compare the size of the aorta measured by CT with the proposed normal value in children and calculating z-scores in the context of MAS. Previous studies, such as the one by Porras et al., described the degree of stenosis as a percentage of stenosis[4]. Although percent stenosis is useful in determining the need for invasive treatment, it has limitations particularly when dealing with diffuse stenosis, where determining the exact location of the stenosis can be challenging. Additionally, the same degree of stenosis can be interpreted differently depending on the length of the proximal stenosis. However, the use of the z-score addresses these limitations and provides a more comprehensive approach for the diagnosis and evaluation of MAS.
In this study, all patients who underwent CT before any invasive treatment of the aorta had a reduced z-score at a certain level, except for Patient 14. While percent stenosis can still be informative in cases of discrete stenosis like Patient 14, it may be more challenging to establish the presence of MAS in cases of diffuse stenosis, even with careful suspicion of the disease, due to the lack of a clear normal reference for aortic size in the pediatric population. Therefore, although it has not been systematically validated in other populations, the normal aortic size and z-score proposed by Hedge et al. may assist in the diagnosis of MAS. Furthermore, when comparing changes in the size of the aorta on follow-up CT, the z-score might be helpful in determining whether the increase in aortic size is commensurate with the growth of the whole body.
In this study, a slightly more favorable blood pressure response was observed in patients with idiopathic MAS, which is a novel finding not previously reported in the literature. However, it is important to consider several potential confounding factors. One limitation is that we did not acquire data related to the severity of RAS, such as the percent stenosis of the renal artery. Only information regarding the presence and laterality of RAS was recorded and included in the analysis. In addition, although not statistically significant, the etiologic group had a higher proportion of bilateral RAS, which might also have been more severe than that in the idiopathic group. Nevertheless, the idiopathic patients also had significantly better outcomes in terms of changes in aortic size.
The intriguing finding of complete improvement in aortic size without invasive treatment in patient 4 highlights the potential for a more conservative management approach in selected patients with idiopathic MAS. Additionally, the unexpected association between the z-score at the common iliac artery (CIA) and aortic size change may be explained by the potential influence of the peripheral arterial beds. Patients with small CIA may also have smaller arteries distal to the CIA, and these smaller lower extremity vessels may have limited the growth of the aorta. This raises questions regarding the growth potential of the hypoplastic aorta, which may be influenced by the size of major branches such as those in the aortic arch, celiac axis, SMA, or CIA, as well as the peripheral vascular beds supplied by these branches. In addition, the poor prognoses associated with aortic size in patients with etiological diagnoses may be partly attributed to an inadequate peripheral vascular bed. To gain more insights into this matter, future studies should employ computational flow dynamics techniques to measure not only the size of the aorta but also the major branches of the aorta. This approach can provide further clarification on the relationship between aortic size and peripheral vascular bed, enhancing our understanding of the underlying mechanisms in these patients.
Considering that 13 of the 16 patients (81.3%) in this study that had follow-up BP measurements also had stage 1 or higher HTN, the overall prognosis for BP appears to be poorer compared to previous studies by other investigators[3–5]. These previous studies reported that many patients achieved successful BP control after invasive treatment, particularly surgery. In our patient series, invasive treatment of the aorta was performed less frequently, which could potentially explain the poorer prognosis than previous studies. Because the idiopathic patients had shorter follow-up durations, it is possible that including further follow-up data from idiopathic patients could have slightly improved the overall prognosis.
Although there have been numerous studies on MAS in the pediatric population, limited information is available regarding its association with LV dysfunction compared to HTN or kidney failure. Porras et al. highlighted the risk of developing congestive heart failure in untreated MAS, particularly during the third or fourth decade, with potentially poor prognoses[4]. They also observed a higher prevalence of LV dysfunction in infants, although the difference was not statistically significant (p = 0.054). Furthermore, in previous reports, cases of LV dysfunction in young patients have been frequently documented, often with a favorable prognosis [5, 13, 14]. Similarly, in our study, most patients with LV dysfunction were under the age of 5, and their cardiac function improved rapidly. However, in patient 7, recurrent LV dysfunction in the third decade of life was not effectively controlled by treatment. Hence, we hypothesized that LV dysfunction in MAS exhibits a bimodal age distribution, with onset typically before the age of 5 associated with a good prognosis, while the second most common onset age is 20 years or older, often associated with poorly controlled hypertension and a poorer prognosis. Furthermore, as reported by Zhao et al., LV dysfunction due to MAS may be misdiagnosed as primary dilated cardiomyopathy[13]. Therefore, particularly in young patients with severe LV dysfunction and relatively normal or elevated blood pressure compared to LV function, MAS should be considered as a potential underlying cause of hypertension.
Limitations
The limitations of this study include the small sample size and variable follow-up durations, which restricted the scope of the prognostic analysis. Additionally, due to the lack of established prognostic indicators for the disease course and CT findings of MAS, the categorization of BP responses and follow-up CT findings was arbitrary.