Coarctation of the aorta (CoA) is a frequent congenital anomaly affecting the heart, in which there is narrowing in aorta with a localized thickening and enfolding so, the blood flow blocked to the descending segment of aorta [1, 2]. The prevalence of CoA is 5% to 8% among children with Congenital Heart Disease (CHD) it might presented as an isolated lesion or in association with the other CHDs [3]. It regarded as the fourth most prevalent heart disease that required surgery or catheterization during early newborn life [4]. Balloon Angioplasty (BA) became an alternative procedure for the management of CoA, which initially performed at 1983 [5]. The effectiveness of BA for the management of native CoA remains controversial in neonates (less than one month) and infants under the first year of life, in spite of its acceptable morbidity and the reduced complication rates. This controversy was due to higher re-stenosis rate and the increased risk of aneurysm formation present with CHF, which might also increase the surgical risk [6]. However, BA stills the less invasive and harmless option than a surgery. The optimistic outcomes of BA could be noticed in peak-to-peak decrease of systolic pressure gradients across the aortic coarctation, widening of the coarcted segment, clinical improvement CHF and reduction of systemic hypertension [7].Several studies reported some short-term and a few intermediate-term outcomes of the BA of previously un-operated aortic coarctation. The recurrence rate of CoA was the main problem in the newborn after BA [8,9]. Furthermore, development of aneurysms at the location of coarctation dilatation was reported [10]. Risk factors which documented for development of re-coarctation are:

• Age less than 12 months

• Aortic isthmus diameter is 2/3 lesser than that of the ascending segment of the aorta located proximal to site of the right brachio-cephalic artery

• The diameter of coarcted aortic segment is 3.5 mm lesser than before dilation 

• Coarcted aortic segment is 6 mm lesser in diameter than after angioplasty. It was further noted that presence of two or more risk factors is associated with high rate of re-coarctation; the larger the quantity of risk factors, the greater is the probability for re-coarctation 

The identification of risk factors may help in choosing patients for BA, so the avoiding or minimizing them could reduce the chance of re-coarctation following angioplasty. The rationale of this work is to study the intermediate and the long-standing effects of BA for native CoA in neonates and infants and to determine any predictive factors for the outcome.

In order to achieve the aim of study, a study design of retrospective cohort was adopted. The study conducted between June 2009 and December 2020. Sixty three neonates and infants who had native, discrete CoA and experienced BA were enrolled. Informed consents were obtained from the parents. The retrieval of the patients’ medical records was permitted by the institutional review board of our institution. Exclusion criteria included previous aortic surgery, other congenital anomalies as hypoplastic left heart syndrome, the great arteries transposition, or univentricular heart. All the patients except two with large Ventricular Septal Defects (VSD) or Patent Ductus Arteriosus (PDA) associated with pulmonary hypertension (mean pressure >40 mmHg) were referred for surgery. Trans-catheter treatment was performed using standard techniques [10]. It is done under general anesthesia. All patients received prophylactic antibiotic treatment with one dose of intravenous cefatriaxone (50 mg/kg). A right coronary catheter (4- or 5- ) French was introduced to reach the descending aorta, so the pressure distal to the CoA was measured. The catheter was then advanced across the CoA with the aid of a 0.025” Terumo guide wire (Terumo Medical Corp., Tokyo, Japan). The pressure in the ascending aorta was recorded. Aortograms were obtained from the lateral plane and 15° left or right of the anterior oblique projection. The diameter of the CoA, isthmus immediately above it and the descending portion of the aorta till the plane of the diaphragm were measured simultaneously. A balloon used was either of a diameter ≤ 1 mm lesser than the size of the isthmus, or not beyond the size of the descending segment. After careful positioning, the balloon was catheter inflated 3−6 times using dilute contrast with average inflation period <15 seconds. If there was insignificant alteration in the lesion or the systolic pressure gradient was still >20 mmHg across the CoA, subsequently a bigger balloon was used. Technical success was described by an instant reduction (<20 mmHg) in peak systolic pressure gradient across the CoA. During follow-up, patients without re-coarctation were selected as group A, while those with re-coarctation were selected as group B. Re-coarctation identified if the systolic pressure gradient was >20 mmHg across the CoA segment. Blood pressure measurement of the upper and lower limbs was performed every month for the first 6 months and every 3−6 months thereafter, during follow-up. Blood pressure of upper limb>lower limb was indicative of suspected re-coarctation. Echocardiography was performed at 3 and 6 months post-BA and then once annually. Peak velocity >2.5 m/s across the previous CoA was regarded as indicative of re-stenosis. Cardiac catheterization with angiography was performed in patients with probable re-coarctation based on Doppler findings. The clinical presentations, laboratory data and outcomes were compared between groups. 

Statistical Analysis

The data were collected and organized in Microsoft Excel (2007) and then the Statistics Package for Social Sciences (SPSS 26.0 for Windows) was used for analyzing the data. Means and the standard deviations were calculated for the numerical data and the proportions for the categorical one. Student’s t-test and the Chi-square analysis were performed for the association and the comparison of parameters between the two groups for the means and proportion respectively. 

Fisher’s exact test, used as appropriate alternative for the calculation of difference if at least, one cell had expected value <5. A p-value ≤0.05 was considered statistically significant.

This study includes 63 patients, 42 males and 21 females with mean age were 3.1±2.8 months. This sample was divided and distributed into two groups A and B; the first group A includes patients without re-coarctation, in contrast to group B which includes re-coarctated patients. The mean age in group A was bigger than that of group B, but the association appeared to be insignificant (p-value = 0.063). Male/female ratio showed predominance of males in both groups but with insignificant difference (p-value = 0.370). The re-coarctation rate was 44.4% of the current study sample. The mean weight (4.300±1.156 kg) in patients with re-coarctation was lower than the weight of patients without re-coarctation; the gradient of systolic blood pressure [11] between the upper and the lower limb continues to be a widely used method to assess the effective management of CoA of the aorta. This gradient before the BA found significantly different between the two groups (p-value = 0.008); the mean gradient was (47.57±14.91 mmHg) in patients among group B with re-coarctation in comparison to (37.43±14.21 mmHg) in group A without. After the BA, the gradient assumed to be significantly reduced (p-value = 0.000) down to 6.371±4.659 mmHg and 13.54±7.54 mmHg in group A and B respectively. The associated cardiac defects were present in 44 (69.8%) of these patients and included 15 patients had patent ductus arteriosus representing (23.81%) of the sample; 8 of them had good results i.e. no re-coarctation, the other associated anomalies were bicuspid aortic valve 13 patients (20.63%), ventricular septal defect 6(9.52%), atrial septal defect only two patients (3.17%) and right aortic arch with aberrant left subclavian artery 1 (1.59%). In addition, nine of the 63 patients had pulmonary hypertension (mean pressure >25 mmHg) before BA. Mean pulmonary artery pressure was 20±14 mmHg (range 12−61 mmHg). Among the patients with these associated anomalies. One patient underwent implantation of Amplatzer duct occluder of PDA during the same procedure. Delayed surgical intervention, performed in tow patients, included VSD + ASD (n = 1), VSD + PDA (n = 1). Twenty one subjects had subsequent trans-catheter elective closure of ASD, VSD, PDA and ten subjects had spontaneous closure of ASD, VSD, PDA or stable hemodynamic status without further treatment. In group B, Asymptomatic right femoral artery occlusion occurred in one patient and four aneurysm formations (6.34%) in the aorta was found by computed tomography but no other complications were found in group A. The children in group B, subjected to re-stenosis during follow-up. One patient (3.5%) had re-stenosis 2 month after BA, two patients (7.1%) at 3 months, two patients (7.1%) at 4 months and two patients (7.1%) at 15 months, 7 patients(25%) at 2 years old, six patients (21%) at 3 years old, two patients (7.1%) at 4 years old and two patients (7.1%)at 6 years old. Three of them were discovered by routine blood pressure measurement and the rest by echocardiography. Only one patient had mild CHF during follow-up. The other twenty seven patients were still asymptomatic two of twenty eight patients underwent subsequent elective surgery. Fourteen patients had another BA (once or twice) eleven of them achieve well result and pressure gradient reduce to less than 20 mmHg. The parents of the remaining patient refused any further treatment. Transverse arch hypoplasia showed minor effect on blood pressure gradient; whereas isthmus hypoplasia is linked with re-intervention in 20.63% of patients. A small aneurysm was noted in 4 (6.34%) patients of 63 Patients. Figure 1 illustrates the distribution of study sample according to age below and above one month and exemplifies that, 46.03% of patients are below one month (29 patients) and 53.97% of them above (34 patients).

Figure 1: Distribution of Study Sample According to Age

Figure 2 shows the distribution of study sample with those children who have been successfully treated with BA and those with re-stenosis which demonstrates that thirty five patients were successfully treated with BA named group A and twenty eight patient developed restenosis after BA named group B.

Figure 2: The Distribution of Study Sample According to Outcome of BA

Figure 3 shows the distribution of study sample with those who have been successfully treated with BA and those with re-stenosis according to age below and above one month and demonstrates that twenty nine patients below one month sixteen patients are complaining from re-stenosis and only thirteen patients are treated successfully. While above one month of age were thirty four patients had BA, twenty two are successfully treated and twelfth patients had re-stenosis.

Figure 3: The Distribution of Study Sample According to Age and Outcome of BA

Table 1 shows the distribution of the study sample and reveals that, the sample includes 42 males and 21 females distributed in two groups; 35 in group A and 28 in group B. The mean age was 3.1±2.8 months, minimum age is 0.36 month, the maximum 11 months and the range is 10.64 months. The sample involves 29 neonates 34 infants. The weights of the sample is ranging 4.2 kg with mean and SD of 4.7±1.3, with minimum weight of 2.8 kg. The Technical success notices in most of the cases. The mean of systolic pressure gradient across the CoA decreased from 41.9±15.3 mmHg to 9.5±7.0 mmHg (p-value = 0.000 and 95%CI 29.00-35.80) after angioplasty and the re-coarctation rate is 44% (28/63). The other demographic and clinical data are demonstrated also.

Table 1: Distribution of Study Sample According to Demographic and Clinical Data

ASD = atrial Septal Defect; BAV = Bicuspid Aortic Valve; BW = Body Weight; ISH = Isthmus Hypoplasia; HAA = Hypoplastic Aortic Arch; F/U = follow-up in months; PDA = Patent Ductus Arteriosus; PGB = Pressure Gradient before Balloon Angioplasty; PGA = Pressure Gradient after Balloon Angioplasty; PS = Pulmonary valve stenosis; RS = Restenosis; VSD = Ventricular Septal Defect

Table 2 illustrates the differences between the risk factors for re-coarctation and depicts insignificant statistically differences between group A and group B in terms of age (p-value = 0.063), gender (p-value = 0.370), associated PDA (p-value = 0.843). Patients in group A, with weight mean of (4.937±1.309) appear to have a good result in comparison with that of group B having weight mean of (4.300±1.156), this difference is just significant statistically (p-value = 0.045).The mean of pre- BA systolic pressure gradient in group B is (47.57±14.91), which is higher than the gradient in group A with a very high significance (p-value = 0.008). Moreover, the mean of the systolic pressure gradient after BA in group A is almost half of that in group B with a highly significant difference (p-value = 0.000). The risk factors for re-stenosis, which is the post-BA systolic pressure gradient >10 mmHg occurs in (85.71%) of group B comparing to (48.57%) of patients in group A (p-value = 0.002) and significant re-stenosis appears among patients with isthmus hypoplasia (p-value = 0.012).

Table 2: Comparison of Risk Factors for Re-Coarctation in Neonates and Infants

* t-test for 2 means **Chi-square test ***Fissure exact test

Table 3 illustrates the distribution of study sample according to the types of balloon used and shows insignificant difference between group A and B regarding the types of balloon used in angioplasty.

Table 3: Types of Balloon used in Angioplasty

*Chi-Square Test for 2 Proportions** Fissure Exact Test 

Figure 4 shows the percentages of types of balloon used in angioplasty in the group A and group B and illustrates that TYSHAK IIis the most frequent among both groups and the Z-MED is the next with 17.14% among group A and 21.42% among group B.

Figure 4: The Percentages of Types of Balloon used in Angioplasty

Being a less invasive option, BA was expected to substitute surgery in managing CoA. Several observational reports and case-matched studies were available, but the number of patients enrolled in each trial is small and the statistical power of most trials is little to report significant differences in clinical outcomes between surgery and BA. CoA accounted in 7% of patients among the children presented with cardiac lesions. Although several congenital anomalies associated with CoA, PDA and VSD were still the frequent coexisting defects. The present study includes 42 males and 21 females with mean age were 3.1±2.8 months. This sample was divided and distributed into two groups A and B; the first group A includes patients without re-coarctation, in contrast to group B which includes re-coarctated patients. The mean age in group A was bigger than that of group B, but the association appeared to be insignificant (p-value = 0.063), similar results were found in work of McElhinney [12] and Lehnert 2019 [13]. The risk of re-coarctation declines gradually with the age, probably secondary to the diverse build up of the vessel wall with decreasing elasticity [14,15]. Male/female ratio showed predominance of males in both groups but with insignificant difference (p-value = 0.370). In Sulaimani cardiac center; 8 cases (61.5%) were females and 5 cases (31.5%) were males, study enrolled 13 cases under age of 2 years who underwent percutaneous balloon angioplasty [16]. The re-coarctation rate was 44.4% of the current study sample. The mean weight (4.300±1.156 kg) in patients with re-coarctation was lower than the weight of patients without re-coarctation; this association could be seen also in several studies [17,18]. Doff et al. [12] considered the weight of children as a continuous variable that correlated with the absolute diameter of the ascending aorta (r = 0.33, p = 0.002) in an inverse associated particularly under the weight of 2.5kg, the result which reported by another studies [19].

Gorbatykh et al. [20] demonstrated that lower weight at repair was a risk factor for re-coarctation and in another study [21] illustrated that the weight was insignificant risk factor when included on a multivariable model with the different surgical strategies. The gradient of systolic blood pressure [17] between the upper and the lower limb continues to be a widely used method to assess the effective management of CoA of the aorta. This gradient before the BA found significantly different between the two groups (p-value = 0.008); the mean gradient was (47.57±14.91 mmHg) in patients among group B with re-coarctation in comparison to (37.43±14.21 mmHg) in group A without. After the BA, the gradient assumed to be significantly reduced (p-value = 0.000) down to 6.371±4.659 mmHg and 13.54±7.54 mmHg in group A and B respectively. In a study conducted in the University of Amsterdam [22] involving 85 patients, the results were parallel in that, the peak to peak systolic gradient across the coarctation decreased from (37±13 SD) to (12±9.5 SD) with (p-value = 0.001) in group A and from (50±22 SD) to (5.4±8.6 SD) with (p-value = 0.001) in groups B. Furthermore, parallel results obtained by some studies [23,24] Susheel et al. [25], by comparing the systolic gradients between groups A and B revealed interesting patterns, which was specifically a higher and increasing gradient for group B till the discharge. Although group B had only a slightly higher mean gradient in comparison with group A (9±3 mm Hg versus 7±5 mm Hg, p-value = 0.10), the gradients in group B continued to be higher. Minor cardiac defects associated with the CoA, such as small ventricular defects, bicuspid aortic valve and left superior vena cava, were addressed as potential risk factors in seven studies [26-29], but none found a significant raise in re-coarctation rates. The results of current work demonstrated that the associated cardiac defects were present in 44 (69.8%) of these patients and included 15 patients had patent ductus arteriosus representing (23.81%) of the sample; 8 of them had good results i.e. no re-coarctation, the other associated anomalies were bicuspid aortic valve 13 patients (20.63%), ventricular septal defect 6(9.52%), atrial septal defect only two patients (3.17%) and right aortic arch with aberrant left subclavian artery 1 (1.59%). In addition, nine of the 63 patients had pulmonary hypertension (mean pressure >25 mmHg) before BA. Mean pulmonary artery pressure was 20±14 mmHg (range 12-61 mmHg). Among the patients with these associated anomalies. One patient underwent implantation of Amplatzer duct occluder of PDA during the same procedure. Delayed surgical intervention, performed in tow patients, included VSD + ASD (n = 1), VSD + PDA (n = 1). Thirty one subjects had spontaneous closure of ASD, VSD, PDA or stable hemodynamic status without further treatment. In group B, Asymptomatic right femoral artery occlusion occurred in one patient and one aneurysm formation in the aorta was found by computed tomography but no other complications were found in group A. The children in group B, subjected to re-stenosis during follow-up. One patient had re-stenosis 2 month after BA, two patients at 3 months, two patients at 4 months and two patients at 15 months, 7 patients at 2 years old, six patients at 3 years old, two patients at 4 years old and two patients at 6 years old. Three of them were discovered by routine blood pressure measurement and the rest by echocardiography. Only one patient had mild CHF during follow-up. The other twenty seven patients were still asymptomatic. Two of twenty eight patients underwent subsequent elective surgery. The parents of the remaining patient refused any further treatment. Transverse arch hypoplasia showed negligible effect on blood pressure gradient; whereas isthmus hypoplasia is linked with re-intervention in 14% of patients. A small aneurysm was noted in 1 (1.5%) patients of 63 Patients. 

BA of native CoA is effective in neonates, infants under the first year of life and also in the older children however in neonates it provides palliative relieve in most of them and another intervention later in life will be required to those with restenosis. The aneurysm formation is rare and however life time follow up is reasonable.

Limitation of Study

This study was limited to the retrospective review of an individual center. Moreover, the follow-up of the cases in our institution might be incomprehensive of all cardiology follow-up, producing a referral bias. Moreover, retrospective design with unbalanced small sample of patients in the 2 groups might have reduced the power to detect differences.

Recommendations

• Further studies needed about the comparison between the angioplasty and the surgery in correcting the CoA and the cumulative survival rate , however if the center when the surgery for low weight and age is not well qualified and develop, we prefer balloon angioplasty of COA, but with close follow up for high rate of recurrence. Unless patients had LV dysfunction our recommendation will be to delay the time of procedure after first few months of age to decrease the risk of recurrence

• Patients with isthmus hypoplasia have major effect on long term gradient relief, so need close follow up for recoarctation

Acknowledgement

The authors would like to thank in advance the managerial of Ibn Albaitar teaching hospital department of congenital cardiac intervention for their cooperation in conducting this research. Also special thanks for ARC-statistical center for their statistical advice and assistance.

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