Structural abnormalities of the medial aorta have been described for conotruncal defects (e.g., tetralogy of Fallot [TOF] and complete transposition of the great arteries (dextrotransposition [d]-TGA). In TOF, progressive aortic dilation is a frequent finding. In patients with d-TGA with an atrial switch, this problem is less often described. The aim of the present study was to compare the extent of dilative aortopathy and aortic distensibility in adults with an atrial switch procedure (n = 39) to that in adults with repaired TOF (n = 39) and controls (n = 39), using cardiac magnetic resonance imaging. The groups were matched for age and gender. Diameters of the aorta indexed to the body surface area were significantly increased in the patients with d-TGA and TOF compared to that of the controls at the aortic sinus up to the level of the right pulmonary artery. On multivariate testing, the diagnosis of a conotruncal defect (β = 0.260; p = 0.003) and aortic regurgitant fraction (β = 0.405; p <0.001) were independent predictors of an increased aortic sinus diameter. Ascending aorta distensibility was significantly reduced in those with d-TGA and TOF compared to controls: 3.6 (interquartile range 1.5 to 4.4) versus 2.8 (interquartile range 2.0 to 3.7) versus 5.5 (interquartile range 4.8 to 6.9) ×10 −3 mm Hg −1 (p <0.001). The independent predictors of ascending aorta distensibility were the diagnosis of a conotruncal defect (p <0.001) and age (p = 0.028). In conclusion, intrinsic aortopathy, manifested as increased ascending aortic diameters and reduced ascending aortic distensibility, is not only evident in adults with TOF, but also in adults with d-TGA and an atrial switch procedure. Long-term follow-up is needed to monitor the aortic size in both patient groups.
Histologic structural abnormalities of the aortic media have been described for patients with tetralogy of Fallot (TOF) and complete transposition of the great arteries (dextro [d]-TGA). In TOF, aortic dilation is a well-defined clinical problem. About 10% of patients with repaired TOF require aortic surgery to prevent aortic dissection or because of progressive aortic regurgitation. Little is known about the structural and functional effect of the histologic abnormalities of the aortic media in adults with d-TGA and a previous atrial switch procedure. We hypothesized that the diameters of the ascending aorta would be similarly enlarged in adults with d-TGA palliated by an atrial switch procedure and those with repaired TOF compared to that of controls. In addition, aortic distensibility is similarly decreased in both groups of patients with congenital heart disease compared to controls. The comparison of patients with congenital heart disease and controls allowed us to validate the accuracy of the methods, and the comparison of patients with d-TGA and those with TOF allowed us to determine the extent of aortopathy in patients with d-TGA in relation to a patient group with conotruncal defects well known to have dilated aortas.
Methods
Cardiac magnetic resonance (CMR) imaging was performed in patients with d-TGA and TOF, according to the treating physician’s request. The control group was recruited from the hospital staff (n = 4) and from patients without structural cardiac disease (n = 35) undergoing CMR. The indications for CMR imaging in controls were to rule out structural heart disease in patients with paroxysmal arrhythmias (n = 6) or to obtain normal values for right ventricular size and function (n = 33). The controls were matched for age and gender with adults with congenital heart defects. All controls had no history of hypertension or previous aortic interventions and were taking no cardiac medication.
The study subjects were examined in the supine position using a 1.5 Tesla (Magnetom Symphony, Siemens Medical Solutions, Erlangen, Germany) or a 3 Tesla (Magnetom Verio, Siemens Medical Solutions, Erlangen, Germany) whole body clinical CMR system. Cardiac synchronization was obtained from 3 electrodes placed on the left anterior hemithorax. A cine steady-state, free precession technique with retrospective gating was used. Typical spatial resolution was 1.5 × 1.5 mm (in plane), with a slice thickness of 8 mm and a temporal resolution of 30 ms.
The aortic root dimensions were assessed in end-diastole from double-oblique images perpendicular to the aorta, as previously suggested, at the following levels: aortic sinus of Valsalva, sinotubular junction, ascending and descending aorta at the level of the right pulmonary artery, aortic arch after the origin of the brachiocephalic trunk, level of the isthmic region, and descending aorta at the level of the diaphragm. All dimensions were indexed to the body surface area. The body surface area was calculated according to the Mosteller formula. As a measure of aortic elasticity, the distensibility of the ascending and descending aorta at the level of the right pulmonary artery was determined from the cine images. Aortic distensibility was calculated as previously reported: (maximal cross-sectional area − minimal cross-sectional area)/minimal cross-sectional area)/(systolic blood pressure − diastolic blood pressure). In addition, in all participants the following CMR data were collected: left ventricular and right ventricular volumes, ejection fraction, and regurgitant fraction of aortic insufficiency. Blood pressure was measured using a syringomanometer in the supine position at the end of the CMR examination. The following clinical data were identified from the patient charts: height, weight, age, medication at the CMR examination, previous interventions, and co-morbidities. No patient had undergone previous aortic surgery.
Between-group comparisons of the categorical parameters were performed using the chi-square test. Between-group comparisons of continuous variables were performed using Student’s t test or analysis of variance followed by Scheffé’s test for post hoc analysis for parametric variables. For nonparametric variables, the Mann-Whitney U test or the Kruskal-Wallis test were used. The correlations were assessed using linear regression analysis. Continuous data were indicated as the mean ± SD or median and interquartile ranges, as appropriate. To assess the independent predictors of aortic dimensions and ascending aortic distensibility, the variables were tested on univariate analysis with aortic sinus and ascending aortic distensibility as the dependent variables. Univariate testing consisted of linear regression analyses for metric and unpaired Student’s t tests for dichotomous, categorical test variables. A threshold p value of <0.1 was used to select candidates for multivariate analysis. A stepwise, multiple linear regression model with backward elimination procedure was chosen to determine the independent predictors of aortic sinus and ascending aortic distensibility in all patients. The statistical significance level was set at a p value <0.05. Analyses were performed using the SPSS, version 18.0, software package (SPSS, Chicago, Illinois) and Prism GraphPad, version 5 (GraphPad Software, La Jolla, California).
For 18 randomly chosen subjects (6 of each group), Bland-Altman and correlation analyses for evaluation of interobserver variability (T.R. and M.F.) were performed. In another 10 patients, an intraobserver variability analysis (T.R.) was performed.
The local ethics committee of the Kanton of Bern, Switzerland approved the study.
Results
The patient characteristics and magnetic resonance imaging findings of cardiac function and volumes are listed in Table 1 . The patient groups and controls were well matched for age and gender. The patient and control age range was 16 to 51 and 16 to 55 years, respectively.
| Variable | TOF (n = 39) | d-TGA (n = 39) | Controls (n = 39) | p Value |
|---|---|---|---|---|
| Male gender | 27 (69%) | 27 (69%) | 27 (69%) | — |
| Age (years) | 29 ± 10 | 26 ± 8 | 27 ± 9 | 0.271 |
| Age at corrective surgery (years) | 0.002 | |||
| Median | 3 | 1 | — | |
| Interquartile range | 1–8 | 0–2 | ||
| Systemic ventricle ejection fraction (%) | <0.001 | |||
| Median | 58 | 47 | 63 | |
| Interquartile range | 54–63 | 43–55 ⁎ | 59–65 † | |
| Systemic stroke volume index (ml · m −2 ) | <0.001 | |||
| Median | 70 | 52 | 52 | |
| Interquartile range | 59–74 ‡ | 46–61 | 47–57 | |
| Blood pressure amplitude (mm Hg) | 50 ± 12 | 48 ± 14 | 48 ± 11 | 0.771 |
| Aortic regurgitation fraction (%) | 0.006 | |||
| Median | 1 | 1 | 0 | |
| Interquartile range | 0–2 | 0–2 | 0–0 § | |
| β Blocker | 4 (10%) | 4 (10%) | — | 1.0 |
| Angiotensin converting enzyme inhibitors/angiotensin receptor-1 antagonists | 5 (13%) | 13 (33%) | — | <0.001 |
| Calcium antagonists | 1 (3%) | 1 (3%) | — | 1.0 |
| Diuretics | 4 (10%) | 5 (13%) | — | 0.085 |
| Body mass index (kg/m 2 ) | 23 ± 4 | 25 ± 5 | 23 ± 4 | 0.098 |
| Body surface area (m 2 ) | 1.8 ± 0.2 | 1.9 ± 0.2 | 1.9 ± 0.2 | 0.032 |
⁎ p < 0.001 to TOF and control groups;
† p <0.03 to TOF and d-TGA groups;
‡ p <0.001 to d-TGA and control groups;
The aortic dimensions of the ascending aorta were significantly larger in the TOF and d-TGA groups than in the controls ( Table 2 ). The absolute aortic sinus diameter was 40 to 49 mm in 7 (18%) patients with TOF, 2 (5%) with d-TGA, and 0 of the controls. One patient with repaired TOF had an aortic sinus diameter of >50 mm, but none of the patients with d-TGA and none of the controls. At the level of the brachiocephalic trunk and descending artery, the aortic dimensions were larger in those with TOF than in those with d-TGA or the controls. In addition to the presence of a conotruncal heart defect, univariate analyses revealed significant correlations of the aortic regurgitation fraction (r = 0.528, p <0.001), systemic stroke volume index (r = 0.418, p <0.001), and age at correction (r = 0.408, p <0.001) with the diameter of the aortic sinus. The systemic ejection fraction and years since corrective surgery were not predictive of aortic sinus size nor treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor-1 antagonists. Because only 4 patients were taking β blockers, we refrained from performing a subgroup analysis for this variable. On multivariate testing, with the presence of a conotruncal defect, aortic regurgitant fraction, and systemic stroke volume as predictive variables, the diagnosis of a conotruncal defect (β = 0.260; p = 0.003) and aortic regurgitant fraction (β = 0.405; p <0.001) were independent predictors of the aortic sinus diameter.
| Variable | TOF Group | d-TGA Group | Control Group | p Value |
|---|---|---|---|---|
| Sinus portion (mm · m −2 ) | <0.001 | |||
| Median | 19.3 | 18.4 | 16.6 | |
| Interquartile range | 18.3–21.7 | 16.9–20.2 | 15.2–17.5 ⁎ | |
| Sinotubular junction (mm · m −2 ) | <0.001 | |||
| Median | 16.7 | 15.1 | 12.6 | |
| Interquartile range | 14.0–18.6 † | 12.9–16.7 | 11.6–14.3 | |
| Ascending (level of right pulmonary artery) (mm · m −2 ) | <0.001 | |||
| Median | 17.7 | 16.5 | 13.7 | |
| Interquartile range | 16.3–20.5 | 13.9–18.9 | 13.2–15.2 ‡ | |
| Brachiocephalic trunk (mm · m −2 ) | 13.2 ± 2.1 § | 11.4 ± 1.7 | 10.9 ± 2.0 | <0.001 |
| Isthmic region (mm · m −2 ) | 9.9 ± 2.0 ∥ | 8.9 ± 1.1 | 9.4 ± 1.5 | 0.029 |
| Descending aorta (at diaphragm) (mm · m −2 ) | 0.03 | |||
| Median | 9.7 | 8.9 | 9.0 | |
| Interquartile range | 8.5–10.5 ¶ | 7.8–9.7 | 8.5–9.7 |
⁎ p <0.002 to TOF and d-TGA groups;
‡ p <0.004 to TOF and d-TGA groups;
§ p <0.001 to d-TGA and control groups;
Distensibility of the ascending aorta was significantly decreased in patients with congenital heart disease compared to the controls ( Table 3 and Figure 1 ) . The distensibility of the descending artery was impaired in the patients with TOF compared to controls but did not differ between those with d-TGA and the controls. Univariate analyses revealed a significant correlation of the ascending aortic dimensions, age, systemic or subaortic ejection fraction, stroke volume index, aortic regurgitation fraction, age at surgical correction, and medical treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor-1 inhibitor with distensibility ( Figures 2 and 3 ) . On multivariate analysis testing, with these variables as predictors, only age (β = −0.182, p = 0.028) and the diagnosis of a conotruncal defect (β = −0.604, p <0.001) were identified as independent predictors of ascending aortic distensibility.
| Variable | TOF Group | d-TGA Group | Control Group | p Value |
|---|---|---|---|---|
| Ascending aorta | ||||
| Relative area change (%) | ||||
| Median | 13 | 14 | 27 | <0.001 |
| Interquartile range | 9–19 | 8–22 | 22–32 ⁎ | |
| Distensibility (10 −3 · mm Hg −1 ) | ||||
| Median | 2.8 | 3.6 | 5.5 | <0.001 |
| Interquartile range | 2.0–3.7 | 1.5–4.4 | 4.8–6.9 † | |
| Descending aorta | ||||
| Relative area change (%) | <0.001 | |||
| Median | 23 | 29 | 32 | |
| Interquartile range | 18–28 ‡ | 23–37 | 26–46 | |
| Distensibility (10 −3 · mm Hg −1 ) | <0.001 | |||
| Median | 5.0 | 6.7 | 7.0 | |
| Interquartile range | 3.3–5.9 § | 3.8–7.9 | 5.5–10.0 |
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