Tetralogy of Fallot (TOF) represents 7–10% of congenital heart disease (CHD), 30-50% of congenital cyanotic heart disease. Advances in surgical repair recently facilitate survival of the affected patients into adulthood with good quality of life [9].
Organized imaging approach is needed not only for identification of the four major malformation of TOF but importantly for precise information about associated extra-cardiac vascular anatomical abnormalities. That information is crucial for surgeons in the formulation of surgical strategies to improve surgical planning and outcomes [10].
No single diagnostic modality suffices for complete evaluation of TOF at any stage. Different diagnostic tools should be used alone or in combination according to the clinical question, the age, size, and clinical condition of the patient, the availability, cost radiation burden of each modality, and the need for sedation and the contraindications for each patient [9].
Cardiovascular magnetic resonance imaging (CMR) is an outstanding imaging tool in assessment of TOF patients, it provides detailed assessment of cardiac and extracardiac morphology, functional analysis (RV size and function, pulmonary valve competence, and pulmonary arterial flow) without radiation or iodinated contrast agents, and is suitable for numerous longitudinal follow-ups. However, it is expensive, long scan time requiring lengthy sedation and anesthesia, and the post-processing is time-consuming. Other disadvantages include artifacts from non-MR-compatible implants, poor evaluation of lungs and airways, and the risk of nephrogenic systemic sclerosis with gadolinium-based products [7].
In the current era, MDCT offers excellent spatial and reasonable temporal resolution providing static and cine imaging as well as 3D reconstructions, thus, it will be very helpful and reliable tool in TOF evaluation [9].
In our study and as regards the role of MDCT in TOF prior to surgical repair, three-step approach was followed, including step (1) recognition of the classic TOF findings, step (2) searching for the surgically relevant findings, and step (3) scanning for other associated congenital anomalies.
Role of MDCT in recognition of classic TOF findings
The degree of overriding aorta was assessed in all patients. This finding is crucial not only in diagnosis of TOF but also for surgical planning of VSD patch closure as patients with double outlet RV will need much larger patch to baffle the blood from the LV to the aortic root [11]. In 60 patients (78%), the degree of the overriding was nearly equal (50:50%). While in 15 patients (19.5%), the aorta arised more from the RV mimicking double outlet RV (TOF variant). Only in 2 patients (2.6%), the aorta arised more from the LV. Statistically significant moderate agreement (k = 0.6) was found between the MDCT and echocardiographic findings; however, the variability in between could be attributed to the visual observation method used in both modalities which would differ depending on the angle that the observer views the aortic valve in relation to the crest of the ventricular septum as explained by Barron et al. [11].
The interventricular septal defects were assessed in all patients. Subaortic outlet perimembranous VSDs were found in all cases show with statistically significant strong agreement with echocardiography. However, additional muscular VSD was detected in 4 cases by MDCT opposite 5 cases by echocardiography. This would be attributed to the very small intermuscular defect that was easier to be detected by color Doppler rather than MDCT. This relatively came in agreement with Barron et al. [11].
The right ventricular outflow obstruction (RVOTO), severity, and level of RVOT obstruction should be adequately evaluated to determine the surgical management of TOF and the age at which it will be carried out [12]. In our study, we found three levels for RVOT obstruction, sub-valvular (infundibular), valvular, and supra valvular (congenital pulmonary stenosis). The sub-valvular stenosis was the most commonly affected level in 71 cases (92.2%). This came in agreement with Agrawal et al. [13] who studied the sites of the pulmonary stenosis at TOF and concluded the sub-valvular pulmonary stenosis was commonly affected at 96%, followed by valvular stenosis at 82%, and lastly supra valvular stenosis at 33.2%.
The patients usually had more than one level of obstruction. Studying level of obstruction in every case showed that combined level of obstruction is much more common than isolated level of obstruction. Combined sub-valvular, valvular, and supra valvular obstruction was found in 36 cases (46.7%), and combined sub-valvular and valvular obstruction in 32 cases (41.5%), isolated sub-valvular obstruction was only found in 3 cases, and isolated valvular obstruction in 2 cases.
The supra valvular obstruction including the MPA and its branches revealed complex anomalies. Four cases had pulmonary atresia (5.1%), one case had atresia of MPA only, two cases showed atresia of the MPA, and its branches, and only one case showed absent MPA and right PA. While the remaining patients showed different degrees of pulmonary artery stenosis: the most frequent anomaly is combined MPA, RT, and left PA arteries stenosis at 14 cases (18%) followed by isolated left PA stenosis at seven cases (9%). This relatively came in agreement with Zakaria et al. [14] who reported incidence of combined MPA stenosis and its branches 17% as the most common pulmonary artery anomaly. While it disagrees with Sheikh et al. [15] who stated that isolated left pulmonary stenosis was the most common abnormality in 10%. This may be attributed to larger number of patients (about 5000) included in the study who underwent cardiac catheterization.
There was difficulty in assessing the degree of agreement between echocardiography and MDCT in evaluation of MPA and RT PA. MDCT could detect focal stenosis at 7 cases (MPA 4 cases and RT PA 3 cases), which was missed by echocardiography. Poor agreement between both modalities regarding left PA evaluation was identified secondary to superiority of MDCT to echocardiography in pulmonary arteries evaluation. Hrusca et al. [12] reported CT accuracy in detection of pulmonary artery defects in 92.1% of cases. Hu et al. [10] reported accuracy of CT up to 100% in detection of supra valvular pulmonary stenosis, they compared their result to cardiac catheterization. Apostolopoulou et al. [9] recommended MDCT evaluation of complex pulmonary artery defects in TOF patients for better visualization pulmonary arteries anatomy, size, and arborization.
As regards the right ventricular hypertrophy (RVH), we noted that all cases showed RVH by MDCT, 52 cases (67.5%) show mild RVH, and 25 cases (32.5%) show marked RVH. While by echocardiography, 58 patients were reported to have RVH by echocardiography with poor correlation in between, k = 0.46. These findings agree with results of Ramanathan et al. [16] who stated that there was poor correlation between echocardiography and MDCT in evaluation of the right-sided heart either by quantitative or qualitative methods. On the other hand, quantitative measurements show very good correlation between both modalities regarding the left side of the heart. This was attributed to the limitation of the echocardiography in evaluation of the right ventricle, in addition to low sensitivity but high specificity of MDCT in evaluation of the cardiac chambers.
Role of MDCT in assessment of the surgically relevant findings
Besides to characterization of the pulmonary arteries, our study provided the surgeons important findings that could formulate the surgical decision, these findings were described as surgically relevant findings and include McGoon ratio calculation, presence or absence of the aortopulmonary collaterals, presence or absence of PDA, and presence or absence of coronary artery anomalies.
As regards McGoon ratio calculation, it is an applicable method to evaluate the pulmonary arterial size and pulmonary blood flow. When the McGoon ratio is adequate, it means enough pulmonary blood, and hence, total surgical correction is planned. Otherwise, palliative operation is suggested in case of inadequate McGoon ratio [17]. In our study, McGoon ratio was calculated in 73 cases by MDCT versus 56 cases by echocardiography with poor agreement in between. This came in agreement with Chen et al. [17] who stated that MDCT with reconstructed oblique images are reliable methods for McGoon ratio calculation when they compared it to the angiographic findings. While transthoracic echocardiography is limited in providing accurate measurements, secondary to small acoustic window, in consistent oblique angle at which it cuts the pulmonary arteries and posterior course of the left pulmonary.
Major aortopulmonary collateral arteries (MAPCAs) are usually present in the most severe forms of TOF. The surgical management of these collaterals aims to restore the normal pulmonary blood flow that is are readily variable depending on patient-specific anatomy [18]. We detected aortopulmonary collaterals at 57 cases(74%). MAPCAs were seen at 22 cases (28.5%) and delicate collaterals were seen at 35 cases (45.5%). At a study done by Juneja et al. [19], they described incidence of the MAPCAs in TOF patients about (56%), but that study included homogenous group of TOF patients with pulmonary atresia, while our study included various congenital pulmonary defects. All cases (22 cases) had origin from the descending thoracic aorta, while 7 cases (31.8%) out of them show additional origin from the aortic arch vessels. All of them show mediastinal course without significant airway compromise and terminate into hila. These detailed quantitative and qualitative findings were not provided by echocardiography. Superiority of MDCT over echocardiography coincides with Chandrashekhar et al. [20] who stated that MDCT had the ability similar to catheterization in aortopulmonary collateral identification, while it is difficult to detect these collaterals by echocardiography mainly secondary to small field of view also.
PDA is a common anomaly in TOF patients, especially in TOF with pulmonary atresia (TOF-PA), when there is ductal dependant pulmonary circulation. Stenting the PDA has gained acceptance for palliation in TOF-PA. However, the complex morphology of the PDA makes the stent implantation more challenging. Hence, this raises the role of imaging in better delineation of the morphology of the PDA [21]. MDCT could detect 27cases (35.1%) with PDA opposite 25 cases (32.4%) detected by echocardiography with strong agreement in between. Yet, their average caliber by CT = 1.19 ± 1.9 versus 0.98 ± 1.4 by echocardiography, with moderate agreement in between. This coincides with Shehata et al. [22] who stated the MDCT was superior to transthoracic echocardiography (TTE) in evaluation of PDA. Also, it was in accordance with Ishehara et al. [23] who recommended MDCT to evaluate doubtful cases for PDA with normal echocardiography, but this study was done in adult patients. While these findings differ from Leschka et al. [24] who reported that TTE is considered the method of choice for diagnosing PDA while MDCT has only a minor role.
Coronary artery anomalies are not uncommon in TOF and should be accurately assessed prior to surgical management. In ventriculotomy or trans annular repair when done to relieve the RVOT obstruction, the aberrant coronary artery passing across the RVOT is reliable to be injured accidentally with poor surgical outcomes [10]. We had 4 cases (5.1%) with anomalous coronary arteries, one of them showed common origin of all coronaries from a single ostium that arise from the right coronary sinus, then divided into LAD passing across the RVOT and RCA in its normal course. It is worth noting that this anomaly had been reported by Beig et al. [25] as a very rare anomaly in the general population with incidence (0.0240 to 0.066%) with more frequent incidence in TOF patients (1.5 to 3.7%).
The second case showed RCA and the left main coronary artery had arised from the right coronary sinus by two separate ostia. The LAD also passed across the RVOT. The third case showed hypertrophied conal branch from the RCA passing across the RVOT. While the last case revealed high take off with angled origin of the RCA. It is worth noting that these findings were not provided at all by echocardiography.
Incidence of coronary artery anomalies (5.1%) coincides with literature as reported by Hrusca et al. [12] that varied from 5 to 12%. However, in their study that had been done to detect anomalous coronary and pulmonary defects in TOF patients, they found coronary artery anomalies in 8 cases (22.2%), they described two out of them with small conal branches from RCA. But these small conal branches are not crucial to be counted from the anomalies as they will not impact the surgery. However, in a study by Hu et al. [10], they described the coronary artery anomalies at 2 cases (2%) with sensitivity 100% and specificity 100% when compared to cardiac catheterization. Also in a study by Zakaria et al. [14], they described only one case of abnormal LAD origin. In our study, MDCT was superior to echocardiography in detection coronary artery anomalies, this coincides with Gotein et al. [26] and Shehata et al. [22].
Role of MDCT in assessment of associated anomalies
As regard TOF-associated findings, we found that MDCT is superior in delineation of the extracardiac vascular anomalies. There were 2 cases that showed abnormal situs (situs ambiguous) of abnormal viscero-atrial relationship. This finding was accidentally noted by MDCT and had not been detected in echocardiography. This may be explained that situs determination needs cardiac, bronchial and abdominal viscera evaluation which is more better by cross-sectional imaging. Although abnormal situs is a rare finding in TOF patients, it was also mentioned by Zakaria et al. [14].
In our study, there were 28 cases (36.4%) that had interatrial septal defects (ostium secondum in 27 cases and ostium primum in only one case). The incidence of ASD in TOF patients is variable in literature, it was reported 3-5% by Beig et al. [25], 10% by Zakaria et al. [13], and 15% by Verma et al. [27]. It was difficult to assess the ASD at 9 cases by MDCT because of motion and respiratory artifacts while they were reported in echocardiography. This is coping with Yasunaga and Hamon [28] who stated that echocardiography is still the gold standard technique for evaluation of the interatrial septum, while MDCT could provide complementary role in large-sized ASD or in delineation of associated extracardiac anomalies. It was noted that 12/28 cases (42.8%) were associated with PDA. This incidence may raise concern to look for PDA in TOF with ASD.
The aortic arch variants and anomalies are not uncommon in the general population and much more common in patients of CHD. Despite AA variants are often asymptomatic and reported as an incidental finding, recently they have been found to pose a greater risk of hemorrhage and ischemia during surgery in the thorax [29]. Variations in the AA type and branching pattern are important to recognize before cardiothoracic surgeries or interventional procedures because they could affect the technique of some of them [30]. In our study, we have found many AA variants in TOF patients. Left-sided AA was found in 55 patients (71.6%) and right-sided AA was found in 22 patients (28.3%). Despite this incidence being cope with many review articles as Lapierre et al. [3] and Zakaria et al. [14] in which RAA incidence about 25 and 30% respectively, this incidence is more or less in accordance with other authors as Hu et al. [10] and Tawfik et al. [30]. They reported incidence of RAA in TOF patients as 18.5 and 37% respectively.
The most common ramification pattern of the left-sided aortic arch was normal branching pattern (brachiocephalic trunk followed by left CCA and left SCA) followed by bovine arch (common origin of brachiocephalic and left CCA) by 40.4% and 22.8% respectively. This came in accordance with Tawfik et al. [30], their incidence was 36% and 16% respectively. In general, the most common ramification pattern of the RAA is aberrant left SCA. However, in our study, RAA with mirror imaging branching pattern was the most common ramification type of RAA by 54.5%. This came in accordance with Hanneman et al. (2017) [31] who stated that RAA with mirror image branching is strongly associated with CHD in up to 98% of cases, including tetralogy of Fallot.
Anomalous pulmonary venous connection are rare but established association with TOF. Total anomalous pulmonary venous return (TAPVR) was reported in some case reports more frequent than partial anomalous pulmonary venous return (PAPVR). This is attributed to embryological basis explained by recent hypothesis. Awareness of anomalous pulmonary venous return in TOF patients is an important issue prior to surgical correction to preclude catastrophic outcomes [32]. PAPVR was detected in one case (1.2%) which was not identified in echocardiography. In this case, two right superior and middle pulmonary veins were seen draining into the SVC, while the remaining right and left pulmonary veins drained normally into the left atrium. In a study done by Chan et al. [33], concluded that repaired TOF patients with unrepaired PAPVR were liable to more RV volume overload and more reduction in RV function.
Also, in our study, MDCT was superior to echocardiography in detection of the PAPVR, this came in accordance with Türkvatan et al. [34]. They stated that MDCT is more reliable than TTE in delineation of the PAPVR likely due to operator dependance and limited acoustic window in delineation of some anomalous pulmonary veins. This is more difficult when the anomalous veins are multiple branching, show high insertion to the SVC, or associated with complex congenital heart disease or enlarged left atrium.
Systemic venous anomalies were found uncommon in TOF patients in our study. It has been found that interrupted IVC with azygos continuation was incidentally noted in 3 cases (3.8%). Two of them had associated with situs ambiguous. Although association between IVC anomalies and TOF had not been reported in literature, Zakaria et al. [14] had also reported one case with double IVC. Persistent LSVC was found in 8 cases (10.3%), left-sided SVC with absent right SVC was found in single situs ambiguous (left isomerism) patient. The prevalence of PLSVC in TOF patients is uncommon, Ari et al. [35] reported in 5.9%, and Nagasawa et al. [36] reported it in 5.1%, these studies are not compatible to some extent with our results (10.3%). Likely, it is attributed to using echocardiography in their studies. In our study, only five cases (4.9%) were detected by echocardiography.
Although retroaortic brachiocephalic vein was described as a very rare anatomical variant in the general population (2/100000) and (5/1000) in CHD by Corno et al. [37], we have found 3 TOF patients (3.8%) with retroaortic brachicephalic vein that also having right-sided AA. Lim et al. [38] published it as a case report in 3-month girl TOF patient using echocardiography. This may be attributed that it is easier to sequentially delineate this venous variant by MDCT than that by echocardiography. Awareness of this venous anomaly is beneficial to avoid transvenous pacemaker or central venous catheter placement from left-arm approach and to minimize perioperative risks [38].
Limitations and recommendations
Although CTA had advantages on morphological imaging, yet it is limited in volumetric and functional analysis of the cardiac chambers and pressure measurement. Taking into account these drawbacks, patients should be carefully selected for CT imaging, and strategies for radiation exposure reduction need to be applied.
