Aortic root dilatation is a well-known feature of unrepaired TOF and is greatest in patients with pulmonary atresia with ventricular septal defect. A medial abnormality coupled with increased aortic flow attributable to the right-to-left shunting is thought to be the pathogenic mechanisms for this dilatation [6, 7]. Aortic regurgitation in TOF imposes volume overload on both ventricles, but more importantly on the right ventricle that also confronts systemic afterload [7]. Aortic root dilatation may lead to aortic regurgitation, which may necessitate surgery [7, 8].

Mild aortic regurgitation is reported in 15–18 % of the patients with repaired TOF [6]. Aortic valve or aortic root replacement is required in a small percentage of these patients [8]. However, remarkable aortic root dilatation was reported with the ratio of observed/expected aortic root size by standard nomogram N = 1.5 in 15 % of adults with repaired TOF (TOF with dilated aorta) (Fig. 17.4) [7]. These patients had special characteristics and manifestation compared with those with < 1.5 of observed/expected aortic root size (those without dilated aorta) (Figs. 17.5, 17.6, 17.7, and 17.8) [7], such as a longer shunt-to-repair interval with a higher incidence of pulmonary atresia, right aortic arch, moderate to severe aortic regurgitation, aortic valve replacement, and increased left ventricular end-diastolic dimensions. In repaired TOF with aortic dilatation study, approximately 15 % of adult patients with repaired TOF had dilated aortic root. Observed to expected aortic root size was 1.7 ± 0.2 in repaired TOF patients with dilated aorta and 1.2 ± 0.2 in those without (Fig. 17.7). Aortic root size was larger than in healthy controls [9] even in those without dilated aorta. Aortic root size markedly increased late after TOF repair in those with a dilated aorta. This dramatic change was far beyond any change expected in healthy controls [9, 10] attributable to increased age. According to aortic dilatation report [7], the cardiothoracic ratio in the patients with dilated aorta was greater than those without. Enlarged left ventricular size was also observed by echocardiography in the patients with dilated aorta. Left ventricular enlargement in adult with repaired TOF is thought to be attributable to previous long-standing left-to-right shunts leading to volume overload. There was no significant difference in left ventricular ejection fraction between those with dilated aorta and those without (Fig. 17.8). Furthermore, there was no relationship between left ventricular size and severity of aortic regurgitation (AR) in patients with a dilated aortic root. It suggests that left ventricular enlargement in an adult cohort of patients with repaired TOF and, in part, a dilated aortic root may be attributable to previous long-standing left-to-right arterial shunts (aortopulmonary shunting) leading to volume overload and not attributable to a direct effect of AR [6].

Risk factors for aortic dilatation and AR in TOF have been analyzed by focusing on hemodynamic abnormalities and patient demographics. Severe cyanosis, severe right ventricular outflow tract obstruction, older age at repair, a larger aortic size at the time of repair, and a history of an aortopulmonary shunt parameters related to long-standing volume overload of the aortic root were the reported risk factors [7]. Right aortic arch, male sex, and the association of chromosome 22q11 deletion were also reported to be risk factors [7, 11]. Tetralogy patients with a right aortic arch tend to have a higher incidence of severe right ventricular outflow obstruction [12]. Males have a lower aortic wall compliance [13]. Currently, repair of TOF is routinely performed during the first year of life in most institutions, negating the need for palliative arterial shunts. Early repair dramatically reduces the period of volume overload of the aortic root and may have a beneficial long-term effect by limiting aortic root dilatation. There was a relation between male sex, pulmonary atresia, right aortic arch, longer time interval from palliation to repair, and progressive aortic root dilatation. In contrast, there was no difference in age at repair or length of follow-up from repair between TOF with dilated aorta and those without. Progressive right ventricular outflow tract obstruction in unrepaired TOF, with the extreme form being pulmonary atresia, increases right-to-left shunt through the ventricular septal defect and in turn the volume overload on the aortic root. In addition, left-to-right shunting attributable to palliative arterial shunts had a significant volume overload on the aortic root and the left ventricle [14], whereas left ventricular ejection fraction remained unchanged. Long-standing volume overload of the aortic root may contribute to aortic root dilatation [6, 15].

There is no gender predominance among patients with TOF [13]. In contrast, there was a clear male predominance among patients with dilated aortic root [7] even after indexing for body surface area and adapting for age [9]. Aortic root size in healthy men is significantly greater than that of healthy women [9, 10]. This was also the case in repaired TOF patients. Aortic elasticity and distensibility are known to decline with age; these changes occur earlier and are accelerated among men [13]. This may also be applicable to TOF patients and may explain in part the male predominance among those with dilated aorta.

Right aortic arch and/or absent pulmonary valve were more frequently observed among those with dilated aorta. Right aortic arch has been reported in 25 % of patients with TOF and is more common in patients with pulmonary atresia with ventricular septal defect [12]. Furthermore, right aortic arch, pulmonary atresia, or absent pulmonary valve syndrome are common morphologic features among TOF patients with 22q11 deletion [16, 17]. This high incidence of right aortic arch (50 %) and pulmonary atresia (19 %) (Fig. 17.5) in patients with marked aortic root dilatation and the relatively common coexistence of absent pulmonary valve syndrome may suggest a possible link between aortic root dilatation and chromosome 22 q11 deletion [18].

Two cases of aortic root dissection in repaired TOF were reported initially from two institutions [19, 20]. The patients were male with an aortic root size of 70.5 mm and 93 × 83 mm, respectively. These are the first reports of aortic dissection in TOF and are important because aortic root dilatation and AR predispose to aortic dissection or rupture that can be fatal, even the number is small. Following these reports of dissection, there are three other reports of dissection in repaired TOF with the aortic root sizes of 55–70 mm [21–23], (Fig. 17.3). Including the other reports on dissection in TOF, minimal aortic root size in TOF patients with dissection was 55 mm (Fig. 17.3).

Because aortic valve or aortic root replacement is occasionally required in repaired TOF [5, 7, 8, 15], meticulous follow-up of the aortic root after repair and timely surgery in patients with aortic root dilatation are recommended.

Independent variables that alter the structure of ascending aortic media include Marfan syndrome, annuloaortic ectasia or Turner syndrome, systemic hypertension [24], aging [25], pregnancy [26], and others (Fig. 17.9). In patients with systemic hypertension, abnormalities of aortic medial elastin and collagen are prevalent [24]. With advancing age, layers of parallel aortic elastic fibers fragment, smooth muscle decreases especially in the thoracic aorta [25]. In pregnancy, gestational changes in ascending aortic media are characterized by elastic fiber fragmentation and hypertrophy/hyperplasia of smooth muscle cells [26]. Marfan syndrome is characterized by a defect in the chromosome 15 gene that codes for fibrillin-1 [27], in the absence of which elastin is more readily degraded by metalloproteinase [28]. Apoptosis reportedly plays a pathogenetic role in the medial abnormalities of abdominal aortic aneurysm [29, 30]. Deletion of transforming growth factor-β (TGF-β) receptor has a relation with aortic dilatation [31]. The genetic fault in Marfan syndrome apparently impairs aortic medial elastic fibers more extensively than impairment in CHD, and the incidence of ascending aortic dilatation, dissection, or rapture is higher, and the degree of aortic root medial lesions is greater in former than the latter [1]^.

So-called cystic medial necrosis of the aortic root has commonly been found in Marfan syndrome, bicuspid aortic valve, and coarctation of the aorta [1]. Patients with a dilated aortic root in TOF share similar histological changes of the aortic root, suggestive of cystic medial necrosis indistinguishable from the aortic root in patients with Marfan syndrome [1]. Higher histologic grading scores in TOF patients are found even in infants, which suggests the intrinsic abnormality has crucial role for this dilatation [32]. Evidence for the role of aortic overflow over time in TOF includes the associations of higher age at operation, pulmonary atresia versus pulmonary stenosis, and longer presence of surgical aortopulmonary shunting with aortic dilation [7, 33]. There is a 12 % increase in mean aortic diameter after surgical aortopulmonary shunting [33].

Furthermore, whether aortic root dilatation is the result of long-standing volume overload of the aortic root or attributable to intrinsic aortic root abnormalities, or more likely both, needs to be additionally investigated.

AR with a dilated aortic root is common in unrepaired or repaired pulmonary atresia with ventricular septal defect [15, 21, 34]. In TOF with pulmonary stenosis, however, when other causes of AR such as infective endocarditis [35], surgical damage of the valve [6, 21], and bicuspid aortic valve [1, 35] are excluded, significant AR is relatively uncommon [6, 36].

AR in unrepaired TOF patients may be due to annular dilation, weaker support of the right coronary cusp by the deficient outflow septum, and cusp prolapse [37]. Only in a very small number of patients can surgical trauma potentiate AR. Frequency and degree of AR can be higher in case of late TOF repair [33].