Several issues pertaining to aortopathy among patients with congenital heart diseases need to be resolved by clinical research (Table 21.1). The incidence and time-dependent changes in aortopathy, especially with regard to the triggered cardiac events including aortic regurgitation, heart failure, ischemic heart diseases, operation, aortic dissection, and death, are not accurately known. Most previous studies [2–5, 16–18] were retrospectively performed in a single institution, leading to distortion of data due to selection and information biases; accordingly multi-institutional prospective studies should be performed. The natural course of aortopathy accompanied by cardiac events, for example, aortic dissection [19], over a patient’s lifetime remains a significant theme in research.

The etiology of aortopathy is complex, probably due to the involvement of multiple related factors and their interactions; hence the process of determining the etiology comprises multiple steps. At first, light microscopic examinations with various stains showed histological abnormalities including fibrosis, cystic medial necrosis, and elastic fragmentation in the aortic wall [6, 7]. To date few studies have used immunohistochemical or molecular-genetic pathological methods; thus, these methods may be encouraging for new studies. When patients undergo reoperation, the biopsied tissue of the aorta can be collected intraoperatively and subjected to detailed pathological examination. Second, hemodynamic factors and cardiovascular function should be investigated, because volume overload [2, 8, 9] and decreased elasticity with increased stiffness [13–15] are associated with aortopathy. Third, although mutations and polymorphisms of fibrillin-1 and matrix metalloproteinase-3 and matrix metalloproteinase-9 [10, 11] were demonstrated in patients with aortopathy, genetic research in this domain remains insufficient. Comprehensive genetic analysis and epigenetic studies taking into account environmental factors such as smoking, diet, and stress provide vistas for further productive research. Fourth, the relation of surgical methods to aortopathy is an attractive research theme, for example, pulmonary artery banding before arterial switch operation [ 20 ] and the procedure of Ross operation [ 21 ].

Echocardiography is essential for research in aortopathy, because aortic dilatation is usually diagnosed on the basis of its findings. The diameter of the sinus of Valsalva and the sino-tubular junction may be measured using the inner edge-to-inner edge technique at mid-systole [22], but in most previous reports [2–5], these measurements were taken using the leading-edge technique at end-diastole [23, 24]. Although the definition of aortic dilatation varies from study to study, the optimal measurement site is the sinus of Valsalva or the sino-tubular junction, with the diameter being the actual diameter adjusted for the body surface area or z-score. A common agreement on a definition of aortopathy is desirable, inter alia, for the purpose of comparing studies.

As aortopathy induces left ventricular hypertrophy and dysfunction, research using techniques such as the speckle tracking method and three-dimensional echocardiography will doubtless prove helpful. Magnetic resonance angiography also plays an important role in clinical practice as well as in research for the assessment not only of aortic dilatation but also of aortic regurgitation, ventricular hypertrophy, and cardiac dysfunction.

The research on medical treatment is clinically important to establish the administration criteria and means of suppressing the progression of aortic dilatation. The administration criteria should be decided on the basis of analysis of risk factors for aortopathy in each disease. As beta-blockers, ACE inhibitors, ARB, and other medications have been experimentally used without evidence, their effectiveness and safety should be confirmed by clinical trials. In particular, ARB is thought to inhibit the activity of transforming growth factor (TGF)-beta related to aortic degeneration and dilatation, holding out the possibility of an effective drug intervention for aortopathy.