Imaging follow-up of tetralogy of Fallot (TOF) patients can be challenging, due to associated thoracic deformities and previous cardiac surgeries. Cardiovascular magnetic resonance (CMR) has an important role in identifying right ventricular outflow tract obstruction, aneurysms, or residual shunts, quantifying pulmonary valve regurgitation or stenosis, and assessing biventricular systolic function. In addition, as first reported by Capelli et al.,1 there is an increasing awareness that aortic dilatation can develop late after TOF repair. Intrinsic histological abnormalities in the aortic root and ascending aortic wall, present since infancy, can contribute to progressive dilatation.2 This possible aortopathy led us to focus our study beyond the aortic root and reinforces the importance of a complete aortic assessment. The accuracy of CMR in the diagnosis of thoracic aortic disease,3 including TOF,4 is unquestionable. Although CMR is expensive, requires long scan duration and has contraindications, it can provide a complete anatomical and functional assessment.5 We sought to assess the ascending aorta (AAo) late after TOF repair and to find possible predictors of AAo dilatation in order to set up an imaging protocol.

A total of 127 adults after TOF repair, not including those with pulmonary atresia, are currently followed as regular outpatients at our tertiary care center. This study prospectively included 78 adults after TOF repair, from March 2011 to December 2015. Inclusion criteria were age ≥18 years, with a time interval since TOF repair of>1 year, and ability to undergo a CMR study. Forty-nine patients were excluded from the study (Figure 1). Exclusion criteria were association with other congenital or acquired heart disease, genetic syndromes, pregnancy, and contraindications for CMR. The aorta was assessed by CMR and an observed-to-expected ratio was calculated based on nomograms from Davis et al.6 The population was divided into two groups: group 1, without AAo dilatation (observed-to-expected ratio ≤1.5); and group 2, with AAo dilatation (observed-to-expected ratio >1.5). CMR measurements were indexed to body surface area according to the Du Bois formula.7

Figure 1.

Graphic representation of the study population and exclusion criteria. CMR: cardiovascular magnetic resonance.

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The demographic and hemodynamic characteristics of the study population are listed in Table 1 and CMR data in Table 2, according to the presence or absence of AAo dilatation. Seventy-eight patients (56% female) were included, with a mean age of 31±10 years. The mean follow-up since TOF repair was 23±7 years. Forty-nine patients were excluded (Figure 1). Of note, 15 patients were excluded due to CMR contraindications or claustrophobia.

The majority (90%) of patients were asymptomatic, seven were in NYHA functional class II and only one was in class III. A right aortic arch was present in 22 patients. In 39 (50%) a systemic-to-pulmonary shunt was performed prior to complete repair, with a median interval of three years. Thirty-eight patients underwent TOF repair with a transannular patch. Surgical repair was performed in adulthood (age ≥18 years) in nine patients (five male and four female). Five patients had systemic hypertension (three in group 2) but systolic blood pressure and pulse pressure were within normal ranges during the study protocol and follow-up. Twenty-five patients were on medication: six on angiotensin-converting enzyme inhibitors, 10 on beta-blockers, and nine on antiarrhythmics (four on amiodarone, two on digoxin, two on propafenone and one on sotalol). LV stroke volume index and LV ejection fraction were within normal ranges. The prevalence of AAo dilatation was 11.5%, with a maximum absolute AAo diameter ≥40 mm in six cases and ≥50 mm in two, but none above 55 mm. The AAo was larger than the sinuses of Valsalva (SoV) in 12.8%. Patients with AAo dilatation were older, predominantly male, with later TOF repair and larger left ventricular mass and volumes. By multivariate analysis (Table 3) LV mass index (LVMI) was the only independent factor associated with AAo dilatation (odds ratio 1.10, 95% confidence interval [CI] 1.01-1.20, p=0.03). A cut-off value of ≥57.9 g/m2 for LVMI had 89% sensitivity and 71% specificity for AAo dilatation (Figure 2).

Figure 2.

Dot diagram for left ventricular mass index according to the presence or absence of AAo dilatation. The horizontal dotted line represents the cut-off point for the best diagnostic accuracy (cut-off ≥57.9 g/m2, with sensitivity of 88.9% and specificity of 71.0%). AAo: ascending aorta; CMR: cardiovascular magnetic resonance; LV: left ventricular; Sens: sensitivity; Spec: specificity.

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Intra- and interobserver variability in cardiovascular magnetic resonance

A sample of 18 randomly chosen cases was reanalyzed. Intraobserver variability of the AAo diameter measurement was 0.42 mm (95% CI: -3.97 to 4.81) (Figure 3a) and interobserver variability was -0.58 mm (95% CI: -4.40 to 3.24) (Figure 3b).

Figure 3.

(a) Bland-Altman plot of intraobserver variability of ascending aorta data by cardiovascular magnetic resonance. Estimated bias 0.42 mm (95% confidence interval -3.97 to 4.81mm). SD: standard deviation. (b) Bland-Altman plot of interobserver variability of ascending aorta data by cardiovascular magnetic resonance. Estimated bias -0.58 mm (95% confidence interval -4.40 to 3.24mm). SD: standard deviation.

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To our knowledge this is the largest prospective CMR study to include only TOF patients without pulmonary atresia. With this exclusion condition we aimed to avoid a potential bias, as in this patient subgroup it is more common to find aortic regurgitation and aortic root dilatation after repair.9 Additionally, we analyzed demographic and anatomical parameters that could be used as predictors of aortic dilation in future research.

A wide range of prevalence of aortic dilatation in TOF has been published. This is probably due to differences in patient selection and definition criteria. Similarly to a previous retrospective study by Kay et al.,10 we defined AAo dilatation as an observed-to-expected ratio >1.5. They found a 6% prevalence of AAo dilatation, but used regression equations developed for computed tomography. In a multicenter study using transthoracic echocardiography,11 the authors reported a 6.6% prevalence of aortic root dilation using the same cut-off ratio for the SoV. In a subgroup of patients the authors had access to the AAo diastolic diameter and reported an estimated prevalence of 18.7% for AAo dilatation, using an absolute diameter cut-off value of ≥40 mm. Although absolute aortic diameters are used for surgical decision,12 adjusting for a gender-specific nomogram derived from a normal CMR reference range appears to be more precise for definition and long-term follow-up in congenital heart diseases, especially in a young population with expected long-term survival. Similarly to previous CMR retrospective studies,10,13 in our cohort eight out of nine patients with AAo dilatation were male. Male gender appears to be the most consistent predisposing factor for AAo dilatation by univariate analysis. However, in our multivariate logistic regression model only LVMI was independently associated with AAo dilatation.

It has been postulated that long-standing volume overload of the aorta before complete TOF repair may be responsible for progressive aortic dilatation. In our cohort, patients with AAo dilatation had higher LV stroke volume index and longer time to TOF repair. Interestingly, nine patients underwent TOF repair in adulthood, due to late diagnosis in four cases (the oldest at age 49 years), and late referral or loss to follow-up during pediatric age in five cases. None showed Ao dilatation at the time of TOF repair. In addition, histopathological abnormalities, mainly in the aortic root and ascending aortic wall, can contribute to aortic dilatation and stiffness in TOF.2,14 Grotenhuis et al.15 and Rutz et al.16 reported aortic dilatation and reduced aortic distensibility as a marker of an intrinsic aortopathy in TOF, compared with normal controls. Alterations in elastic properties were especially found in the proximal aorta,17 and were thought to precede aortic dilation and to increase LV afterload.18,19 Consequently, TOF aortopathy can lead to LV remodeling as a result of ventricular-arterial coupling. Increased LV end-diastolic pressure due to increased LV volumes and afterload could explain why in our study patients with AAo dilatation had a higher LVMI. Moreover, systemic hypertension was more prevalent in the dilated group, although pulse pressure and systemic arterial compliance were similar in the two groups, possibly reflecting good blood pressure control under medication. These findings highlight the need for regular clinical follow-up along with careful imaging follow-up of the aorta and LV parameters, including LV size and function, after TOF repair. We found a larger aortic diameter at the level of the AAo in 13% of patients, demonstrating the importance of complete aortic screening. Although echocardiography is relatively inexpensive, portable and widely available, it has limitations concerning AAo imaging. CMR and computed tomography are the current gold standard for a complete aortic assessment, however CMR imaging has the advantage of avoiding exposure to either radiation or iodinated contrast, compared to computed tomography, in young patients in need of long-term follow-up. The role of CMR for TOF follow-up is unquestionable due to its accuracy and reproducibility. A comprehensive CMR acquisition after TOF repair enables not only screening for residual RV outflow tract and pulmonary valve lesions, but also assessment of right and left ventricular parameters, including LV mass and volumes, and can accurately provide serial aortic diameters. A slow rate of aortic diameter progression in TOF has been reported,10,13 but with a higher rate of progression in the AAo.13 It has been proposed that CMR imaging of the aorta should be repeated every three years if the aorta is not dilated at baseline.10 Although aortic dissection is rare, it can occur long after TOF repair. In the first such case, aortic dissection was reported beginning in the AAo in a 30-year-old man who had undergone TOF repair nine years before.20 To prevent this complication, a complete assessment of the thoracic aorta should be included in a CMR imaging protocol for TOF. Based on our findings, we suggest a careful imaging follow-up of the AAo after TOF repair, especially in males, older patients, and those with later TOF repair and larger left ventricles.

AAo assessment as part of a routine CMR study after TOF repair is recommended to prevent future aortic complications, particularly in males, older patients, and those with later repair and larger left ventricles. LVMI assessment has potential as a screening tool for AAo dilatation with future clinical implications.

The authors have no conflicts of interest to declare.