Aortic root dilatation is frequently encountered in adults with repaired Tetralogy of Fallot (TOF). The timing of total repair is known to have a significant correlation with late aortic root dilatation, but it is not well established. The objective of this study was to investigate the risk factors and correlation with timing of total repair for aortic root dilatation in adults with repaired TOF. An observational retrospective cohort study was conducted in 314 adults (≥ 18 years) with repaired TOF. Aortic root dilatation was defined when the absolute diameter of Sinus of Valsalva (SoV) was over 40 mm. SoV was measured by echocardiography in 110 patients, computed tomography angiography in 168 patients, and magnetic resonance image in 36 patients. Aortic root dilatation was observed in 65 patients (20.7%). Among them, 3 patients underwent Bentall operation due to acute aortic dissection or aortic root aneurysm. On multivariate logistic regression analysis, age at total repair was a significant risk factor for late aortic root dilatation (OR = 3.14; 95% CI 1.62–6.08; p = 0.001) and the cutoff value of age was 1.9 years. However, late aortic root dilatation was also observed in 10% of patients (10/91) who operated before 1 year of age. Late total repair was a significant risk factor for late aortic root dilatation in repaired TOF. However, early total repair did not always prevent late aortic root dilatation. These results suggest that congenital aortic pathology may also be a possible cause of aortic root dilatation along with longstanding hemodynamic stress.
Hinweise
The original version of this article was revised due to a retrospective open access cancellation.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Introduction
Aortic root dilatation is a known clinical feature of unrepaired Tetralogy of Fallot (TOF) [1, 2]. Hemodynamic stress on the aortic wall before repair may play a role in progressive aortic dilatation [1]. Increased and altered flow through the overriding aorta and uneven sharing of conotruncal tissue between the aorta and pulmonary artery may contribute to aortic root dilatation [3]. Aortic root dilatation is also observed in adult patients late after repair of TOF [2‐6]. This may result from another mechanism of intrinsic aortopathy similar to what is seen in Marfan syndrome [7‐10]. Intrinsic histologic changes ranging from medionecrosis, fibrosis, cystic medial necrosis, and elastic fragmentation to elastic lamella disruption in the aortic wall of TOF patients are also observed even at early infancy [8].
The prevalence of aortic root dilatation in adults with repaired TOF ranged from 15 to 51% according to various criteria of aortic root dilatation [2‐6]. Risk factors for this clinical feature have not been well documented [3‐6]. The timing of total repair is known to have a significant correlation with late aortic root dilatation, but it is not well established. Late total repair was a significant risk factor for late aortic root dilatation in several reports [6, 11], while others did not [3‐5]. Some studies suggest that early total repair of TOF could prevent late root dilatation [10, 11]. The objective of this study was to investigate the risk factors for aortic root dilatation in adults with repaired TOF and to correlate with timing of surgery. We also examine its clinical implication by confirming the incidence of significant aortic regurgitation, aortic dissection, or aneurysm that requires surgery.
Anzeige
Materials and Methods
Study Design and Patient Population
This is a retrospective observational cohort study. Adult patients (≥ 18 years of age) with surgically repaired TOF or pulmonary atresia with ventricular septal defect who were evaluated at our institution between January 2009 and December 2015 were enrolled in this study. Patients who received echocardiography, cardiac computed tomography (CT), or magnetic resonance imaging (MRI) after 18 years old were included in this cohort. This study was approved by our Institutional Review Board (2016-175). Patients were excluded if they had coexisting complex anomalies such as major aorto-pulmonary collaterals (MAPCA) and atrioventricular septal defect (AVSD) or incomplete imaging data. A total of 377 patients were initially identified. Among them, 63 patients were excluded according to the exclusion criteria (MAPCA in 10, AVSD in 6, and incomplete imaging data in 47). Therefore, a total of 314 patients were enrolled in the final analysis.
Aortic root diameter is affected by several factors, including patient age, sex, and body size [12‐14]. Considering these variables, several definitions of aortic root dilatation have been used in previous studies [3‐6]. We adopted only one criterion of aortic root dilatation considering the upper normal limit to avoid complexity and obscurity [12]. Aortic root dilatation was defined when an absolute diameter of Sinus of Valsalva (SoV) was greater than 40 mm.
Measurement of Aortic Root
The diameter of SoV was measured using one of the most recent imaging modalities of echocardiography, CT, or MRI (Fig. 1). If these modalities existed in the similar period, CT was adopted first. The measurements were reviewed by two blinded experienced readers. For patients who had undergone aortic root surgery during follow-up period, data from their last preoperative CT were used for analysis. Four aortic components (aortic annulus, SoV, sinotubular junction, and ascending aorta) were measured. On echocardiographic finding, these parameters were measured in a parasternal long-axis view in diastole using the leading edge-to-leading edge technique [15]. Otherwise, they were measured at the standard anatomic landmarks perpendicular to the axis of blood flow using 3D reconstruction images on CT or MRI findings [16]. Aortic valve regurgitation was quantified as absent, mild, moderate, and severe by Doppler characteristics and color flow mapping according to the American Society of Echocardiography recommendations [17].
Fig. 1
Measurement of aortic components: A Cardiac CT, B cardiac MRI, C Echocardiography. a: aortic annulus; b: Sinus of Valsalva; c: sinotubular junction, d: ascending aorta. Measurements were undertaken perpendicular to the longitudinal or flow axis of the aorta to correct for the variable geometry of the aorta
×
Statistical Analyses
Continuous variables are presented as mean ± standard deviation, while categorical variables are presented as frequency (percentage). Comparisons of continuous variables between two groups were performed by using Student t tests. Comparisons of categorical variables between two groups were performed using Pearson Chi-square test or Fisher’s exact test. Relationships between continuous variables were analyzed using Pearson correlation coefficients. Risk factors for aortic root dilatation were assessed with univariate and multivariate logistic regression analyses. Variables to be high relationships (age and age at total repair) were excluded in multivariate analysis. We used stepwise variable selection method. A receiver operating characteristic curve (ROC) was used to evaluate the cutoff value of age at repair for the occurrence of aortic root dilatation. All reported p values were two-sided, and p < 0.05 was considered statistically significant. Statistical analyses were performed by using SPSS Statistics 20 (SPSS, Inc, Chicago, IL, USA).
Anzeige
Results
Patients
The median age of the entire cohort was 22 years (range, 18 to 71 years) and the median follow-up duration after total repair was 19.2 years (range 0.9 to 41.5). Eighteen patients underwent total repair at other institutions. The median age at total repair was 1.6 years (range, 0.3 to 59 years). Eighty-seven patients did not receive other surgical procedures after total repair until the last follow-up. During the follow-up period, 211 patients underwent pulmonic valve replacement (PVR), 30 of them underwent PVR more than twice at our institution. Other operations were also performed, including the closure of residual ventricular septal defect (VSD) in 12, permanent pacemaker insertion in 11, relief of right ventricular outflow tract in 3, Bentall operation in 3, change of right ventricle to pulmonary artery conduit in 2, lobectomy in 1, and tricuspid valve replacement in 1.
Prevalence of Aortic Root Dilatation
The prevalence of late aortic root dilatation was 20.7% (65/314). Among them, 11 patients had aortic root diameter ranged from 45 to 50 mm, and 7 patients had aortic root diameter ≥ 50 mm.
Baseline characteristics according to the presence or absence of aortic root dilatation are summarized in Table 1. Patients with aortic root dilatation were older and more likely to be males with larger body surface area (BSA) than those without aortic root dilatation. Total repair was performed at older age. More patients underwent shunt operation before total repair. The diagnosis of pulmonary atresia or right aortic arch was more common. On last echocardiographic finding, larger left ventricular end-systolic and end-diastolic diameter was observed. Other aortic parameters such as annulus, sinotubular junction, and ascending aorta also tended to be larger in patients with aortic root dilatation. Residual VSD was more common. The prevalence of moderate aortic regurgitation was not significantly different between the two groups with or without aortic root dilatation.
Table 1
Baseline characteristics of patients according to aortic root diameter
SoV (≥ 40) n = 65
SoV (≤ 40) n = 249
p value
Age (year)
33 ± 13
24 ± 7
< 0.0001
Sex (male)
54 (83.1%)
134 (53.8%)
< 0.0001
Previous shunt
19 (29.2%)
37 (14.9%)
0.007
Duration of shunt (year)
2.8 ± 2.8
1.4 ± 1.4
0.06
Age at repair (year)
12 ± 15
3 ± 6
< 0.0001
BSA (m2)
1.7 ± 0.2
1.6 ± 0.2
0.001
LVEDD (mm)
48.8 ± 6.6
45.3 ± 5.6
< 0.0001
LVESD (mm)
32.2 ± 7.5
29.4 ± 5.9
0.002
Aortic annulus (mm)
26.5 ± 3.8
22.2 ± 2.6
< 0.0001
Sinus of Valsalva (mm)
44.2 ± 6.6
32.6 ± 3.6
< 0.0001
Sinotubular junction (mm)
35.7 ± 5.1
27.2 ± 3.7
< 0.0001
Ascending Aorta (mm)
35.2 ± 5.8
26.9 ± 4
< 0.0001
Right aortic arch
7 (10.8%)
10 (4%)
0.033
Moderate AR (> Gr2)
4 (6.2%)
5 (2%)
0.093
Residual VSD
7 (10.8%)
9 (3.6%)
0.02
LV dysfunction
6 (9.2%)
11 (4.4%)
0.127
Pulmonary atresia
8 (12.3%)
7 (2.8%)
0.001
SoV Sinus of Valsalva, BSA body surface area, VSD Ventricular Septal Defect, LVEDD Left Ventricular End Diastolic Dimension, LVESD Left Ventricular End Systolic Dimension, AR aortic regurgitation, Gr grade, LV left ventricle
Risk Factors for Aortic Root Dilatation
In order to analyze the effect of age at total repair, cutoff value for risk factor was calculated by using the ROC curve. The predictive value of age at total repair for late aortic root dilatation showed an area under the curve (AUC) of 0.686, with a sensitivity of 66.2% and a specificity of 64.3% in ROC analyses. The optimal cutoff value for age at total repair was 1.9 years (Fig. 2).
Fig. 2
Receiver operating characteristic curve (ROC) analysis. The optimal cutoff value of age at total repair for late aortic root dilatation was 1.9 years. Area under the curve (AUC): 0.686; sensitivity: 66.2%; specificity: 64.3%
×
Risk factors associated with aortic root dilatation are listed in Table 2. On multivariate analysis, age at total repair > 1.9 years (OR = 3.14; 95% CI 1.62–6.08; p = 0.001), male sex (OR = 3.82; 95% CI 1.71–8.51; p = 0.001), and pulmonary atresia (OR = 4.36; 95% CI 1.22–15.59; p = 0.023) were signification risk factors for late aortic root dilatation.
Table 2
Risk factors associated with aortic root dilatation
Univariate
Multivariate
OR
95% CI
p
OR
95% CI
p
Age, per year
1.08
1.05–1.11
< 0.0001
Male sex
4.15
2.07–8.30
< 0.001
3.82
1.71–8.51
0.001
Age at repair > 1.9 year
3.51
1.98–6.25
< 0.001
3.14
1.62–6.08
0.001
Pulmonary atresia
4.85
1.69–13.93
0.003
4.36
1.22–15.59
0.023
Previous shunt
2.37
1.25–4.48
0.008
1.87
0.63–5.52
0.256
Duration of shunt, per year
1.47
1.14–1.89
0.003
1.06
0.75–1.50
0.744
BSA ≥ 1.8 m2
2.21
1.23–3.85
0.005
1.62
0.83–3.16
0.16
Right aortic arch
2.88
1.05–7.90
0.039
2.01
0.67–6.09
0.216
Residual VSD
3.21
1.15–8.96
0.026
3.13
0.92–10.59
0.067
LVEDD, per mm
1.1
1.048–1.15
< 0.0001
LVESD, per mm
1.07
1.02–1.11
0.004
1.02
0.97–1.07
0.541
Moderate AR
3.2
0.834–12.28
0.09
1.75
0.34–9.15
0.506
LV dysfunction
2.2
0.78–6.19
0.14
BSA body surface area, VSD Ventricular Septal Defect, LVEDD Left Ventricular End Diastolic Dimension, LVESD Left Ventricular End Systolic Dimension, AR aortic regurgitation
Correlation Between Total Repair Timing and Late Aortic Root Dilatation
The frequency of late aortic root dilatation according to age at total repair is shown in Fig. 3. A total of 91 patients underwent early total repair before 1 year of age and 10 patients (11%) had late aortic root dilatation. Four of these patients had risk factors such as pulmonary atresia in one, previous shunt surgery in 3, and right aortic arch in one. However, the other six patients had no particular risk factors. The predicted probability curve for aortic root dilatation with age at total repair is shown in Fig. 4. As the age at total repair increased, the probability of late aortic root dilatation increased.
Fig. 3
The frequency of late aortic root dilatation according to age at total repair (age: years)
Fig. 4
The predicted probability curve for aortic root dilatation with age at total repair
×
×
Late Aortic Event
Patients with aortic root diameter ≥ 50 mm are summarized in Table 3. Three patients underwent aortic root surgery with Bentall operation. One of them developed acute aortic dissection and severe aortic regurgitation at the age of 32 years (10 years after total repair) (Fig. 5). Another patient developed aortic root aneurysm and severe aortic regurgitation at the age of 36 years (17 years after total repair). The pathologic findings of the patient’s aortic wall were fragmentation of the internal elastic lamina and the medial elastic tissue network. The last patient who had undergone aortic valve replacement at the time of total repair developed huge aortic root aneurysm at the age of 65 years (22 years after total repair). The remaining four patients were followed up regularly.
Table 3
Patients with Sinus of Valsalva ≥ 50 mm
No
Sex
Previous op. before total repair
Total repair
Last follow-up
Age (year)
Root (mm)
Age (year)
Root (mm), AR
Aortic procedure
1
M
LMBT (at 8 year)
Palliative RVOTR (at 16 year)
19
35.1
36c
53, severea
Bentall
2
M
None
27
33.4
40
51, moderate
None
3
M
None
22
31.6
32c
65, severea
Bentall
4
F
RMBT (at 10 year)
13
N/A
38
54, mild
None
5
M
None
44
49
46
52, mild
None
6b
M
None
43
N/A
65c
85, AVR statea
Bentall
7
M
None
0.8
22
18
50, mild
None
N/A: aortic root measurement was impossible because of missing data
M male, F female, TOF Tetralogy of Fallot, LMBT Left modified Blalock–Taussig shunt, RVOTR Relief of right ventricular outflow tract obstruction, RMBT Right modified Blalock–Taussig shunt; y year; AR aortic regurgitation, Root aortic root diameter
aMeasured value just before aortic procedure
bPatient 6 underwent aortic valve replacement at a time of total repair simultaneously
cAge at aortic procedure
Fig. 5
A 32-year-old male patient who had undergone TOF total repair at the age of 22 developed acute aortic dissection and severe aortic regurgitation. He underwent Bentall operation successfully. (a Preoperative cardiac CT image. b Postoperative cardiac 3D CT image)
×
Discussion
Age at total repair was a strong risk factor for late aortic root dilatation in our cohort. The predicted probability of late aortic root dilatation also increased with age at total repair. Hemodynamic stress with increased aortic flow prior to definitive repair was one of the major mechanisms for aortic root dilatation in unrepaired TOF [2]. When a total repair was performed at a later age, the longstanding hemodynamic stress through the aorta might increase the possibility of the aortic root dilatation. In particular, when total repair was undergone in adulthood, late aortic root dilatation was found to be more frequent and severe. In this study, there were seven patients with aortic root diameters greater than 50 mm, and all but one patient were undergone a total repair in adulthood. Among them, three patients underwent aortic root surgery due to aortic dissection or aneurysm. Therefore, special surveillance would be required for patients who had undergone TOF total repair in adulthood, since the aortic root could be increased after total repair to the extent that surgical intervention was necessary.
Anzeige
Several reports suggested that earlier repair within the first year of life may prevent aortic root dilatation in TOF patients after analyzing aortic root diameters through serial echocardiographic images [10, 11]. However, in this study, late aortic root dilatation was identified in 10 of 91 patients who underwent total repair before 1 year of age. Moreover, six of them had no particular risk factors. These results suggest that congenital aortic pathology may also be a possible cause of aortic root dilatation along with longstanding hemodynamic stress.
Male sex was also a significant risk factor for late aortic root dilatation. Aortic size in normal patients is affected by body surface area, age, and sex, with male sex being the most consistent factor [18]. It has been reported that males with congenital heart disease have an increased risk of aortic aneurysms and dissections with higher probability of requiring surgery when compared to females [18]. Pulmonary atresia was another significant risk factor for late aortic root dilatation. Patients with pulmonary atresia showed excessive flow through the aorta before repair. Disproportionate sharing of conotruncal tissue between aorta and pulmonary artery might favor aortic growth and dilatation [19].
There is some controversy about the clinical implications and management strategy for dilated aortic root in repaired TOF. Although the incidence of aortic root enlargement is relatively common, there are no evidences of prophylactic aortic surgery for connective tissue diseases such as Marfan syndrome [20, 21]. Therefore, the strategy for enlarged aortic root is similar to general ACC/AHA guidelines according to the significance of aortic valve regurgitation. According to the American College of Cardiology/American Heart Association (ACC/AHA) thoracic aorta guidelines [16], for patients without congenital heart disease or a connective tissue disorder, aortic root surgery is indicated when the aortic diameter exceeds 55 mm. In aortic valve replacement (AVR), aortic root surgery is recommended if the diameter exceeds 45 mm irrespective of underlying aortic pathology.
Study Limitations
There are several limitations in this study. First, this study was retrospective in nature. Second, the measurement of SoV was performed using three different tools. Therefore, measurement error might exist between the tools. Third, interobserver variability might exist because two observers measured the diameters of aortic parameters. Fourth, selection bias might exist because we only enrolled patients who could be followed up for latest 5 years. Fifth, medical factors affecting aortic dilatation such as hypertension, collagen diseases, gestational history, and smoking have not been identified.
Anzeige
Conclusions
Aortic root dilatation was not uncommon and the incidence was 20.7% in adults with repaired TOF. The risk factors for late aortic root dilatation were age at total repair > 1.9 years, male sex, and pulmonary atresia. When total repair was undergone in adulthood, late aortic root dilatation was found to be more frequent and severe. However, early total repair did not always prevent late aortic root dilatation. These results suggest that congenital aortic pathology may also be a possible cause of aortic root dilatation along with longstanding hemodynamic stress.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethical Approval
Ethical approval was waived by the local Ethics Committee of Sejong general hospital in view of the retrospective nature of the study and all the procedures being performed were part of the routine care (No. 2016-175).
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Mit e.Med Pädiatrie erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Pädiatrie, den Premium-Inhalten der pädiatrischen Fachzeitschriften, inklusive einer gedruckten Pädiatrie-Zeitschrift Ihrer Wahl.
Mit e.Med Innere Medizin erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Innere Medizin, den Premium-Inhalten der internistischen Fachzeitschriften, inklusive einer gedruckten internistischen Zeitschrift Ihrer Wahl.
