Management of collaterals after Glenn procedure and its impact on patients with a single ventricle: a single-center study

INTRODUCTION

The occurrence of congenital heart disease is between 6 and 13 per 1000 live births.1 In developed countries, prenatal diagnosis is currently used to detect congenital heart disease (CHD) before birth. In developing countries, only a minority of children with CHD are detected and few benefit from surgical treatment, causing a pattern of late presentation accompanied by a high complication rate.2

The term single ventricle is generally used to describe any CHD with 1 functioning ventricle, including double inlet left ventricle, single ventricle, common ventricle, and univentricular atrioventricular (AV) connection. Other lesions, such as hypoplastic left heart syndrome (HLHS), tricuspid atresia, unbalanced AV septal defect, mitral atresia with normal aortic root, and heterotaxy syndromes with 1 functioning ventricle, can also be added to this group.3

The bidirectional Glenn shunt (BDG) and hemi-Fontan are surgical techniques used to create a superior cavopulmonary anastomosis (CPA) in patients with an anatomic or functional single ventricle. Whether it is right or left, the single ventricle must provide blood supply to the higher resistance systemic circulation and the lower resistance pulmonary circulation until surgical correction is undertaken. The BDG procedure or hemi-Fontan helps to eliminate the volume load on the single ventricle and facilitate subsequent Fontan surgery.4

Systemic venous collateral channels in patients with univentricular hearts after CPA or Fontan operations may cause significant systemic desaturation. After CPA, the pressure difference between the superior vena cava (SVC) and inferior vena cava leads to the development of venous connections between the 2 systems to decompress elevated pressure in the SVC system. Venovenous collaterals can emerge at any time following the CPA.5

Evaluation for venous collaterals should be performed routinely in all patients undergoing pre-Glenn and pre-Fontan catheterization. Venovenous collaterals draining below the heart will be separated from the systemic circulation after Fontan completion. These collaterals need not be embolized unless the patient has an interrupted inferior vena cava with the exclusion of the hepatic veins from the Fontan circulation, as in the Kawashima operation. In contrast, venovenous collaterals that drain into pulmonary veins or the atrium will continue to cause cyanosis due to right-to-left shunts and should be embolized.6

Spicer et al.7 reported an 84% incidence of aortopulmonary collaterals (APC) in children undergoing pre-Fontan cardiac catheterizations. APCs developed in the univentricular heart often have extensive communication and commonly involve networks of smaller lacy vessels between larger collaterals. Total closure of the APCs is not feasible in such situations. In addition, extensive embolization of all APCs adds to the total catheterization procedure time and potential complications without further clinical benefit. Bradley et al.8 recommend selective embolization of moderate to large APCs in patients undergoing univentricular heart repair. Furthermore, the pulmonary blood flow supplied by the APCs may be important in cyanotic patients. Closure of APCs in such patients may decrease the systemic saturation to dangerously low levels.

We aimed to register all patients referred to our hospital following BDG from March 2022 to February 2023. We conducted a full assessment of their hemodynamics and collateral channels, including venovenous collaterals to systemic veins or pulmonary veins and APCs. We also explored different management methods and evaluated the impact of this management on patients with single-ventricle physiology.

METHODS

The study included 56 patients who underwent BDG. We excluded critically ill patients. All patients underwent a comprehensive medical history, which included demographic data (current age, sex, weight, height, body surface area), perinatal history, developmental history, history of venesection, history of hospitalization, and surgical data. The surgical data included age at the time of the intervention, date of intervention, and any other surgical procedures performed prior to BDG, such as previous pulmonary artery banding or a modified Blalock-Taussig (MBT) shunt. The history also included information on previous invasive hemodynamic studies, previous transcatheter interventions (such as pulmonary artery stenting or closure of venovenous collaterals), and current medical treatment. The clinical examination consisted of assessing arterial blood pressure, pulse, respiratory rate, and baseline SaO₂. We also conducted a local cardiac examination, observation of subcutaneous superficial collaterals on the chest, and examination of thoracic scars. Heart sounds and murmurs, as well as both lungs, were auscultated. Twelve-lead surface electrocardiography was performed to assess heart rate and rhythm, axis, the presence of any conduction disturbances, and arrhythmias. A chest X-ray was performed to assess the cardiac shadow, pulmonary vasculature, and the presence of previous stents, embolization devices, and sutures from previous sternotomy.

A full transthoracic echocardiographic examination was performed to determine cardiac and visceral situs, the location of the cardiac apex, AV and ventriculoarterial connections, the relationship and abnormalities of the great vessels, description of the AV connection as being double inlet, atresia of 1 of the inlets, or a common AV valve, description of the ventriculoarterial connection, and determination of the morphology and systolic function of the dominant ventricle (right, left, or indeterminate).

Available multislice computed tomography data were included to confirm the anatomy, determine systemic and pulmonary venous drainage, evaluate the peripheral pulmonary tree, assess the BDG size and patency, and determine the presence of venovenous collaterals and APC. Routine laboratory investigations were conducted before catheterization, including a complete blood count, international normalized ratio, kidney function tests, and virology.

Invasive cardiac catheterization involved a complete hemodynamic study of patients before Fontan completion and desaturated patients. The procedure was performed under 100% oxygen supplementation. The usual access points were the right femoral artery and right or left subclavian veins. Injection of the BDG was carried out in the posteroanterior (PA) view to assess BDG patency and the size of the pulmonary tree. Innominate vein injection in the PA view was used to assess the presence of venovenous collaterals. Descending aorta injection in the PA view was conducted to determine the presence of APC. Pressures and saturations were recorded from various cardiac chambers.

Percutaneous interventions were performed when indicated, including peripheral pulmonary stenting or closure of venovenous collaterals or APC. Venovenous collaterals were only closed in desaturated patients who were not candidates for Fontan completion (due to impaired ventricular function, severe AV valve regurgitation, or mean pulmonary artery pressure [PAP] > 14 mmHg), after excluding patients with pulmonary hypertension or SVC syndrome. Major APCs were closed in patients with evidence of ventricular volume overload (eg, elevated ventricular end-diastolic pressure), causing back pressure on pulmonary veins and arteries.

Statistical analysis

Qualitative data are expressed as frequencies and percentages and quantitative data as mean ± standard deviation. A standard t-test, 1-way analysis of variance, and independent samples t-test were used. Linear regression and Pearson correlation analysis were used to determine the correlation of variables of interest. The data were analyzed using commercially available software (SPSS version 19.0), and P < .05 was considered statistically significant. All data and materials from the study are available upon request.

RESULTS

Our registry included 56 patients who underwent BDG and were referred to our hospital between March 2022 and February 2023. The median age of the patients was 9.67 (7.42-12.17) years (min-max, 2.25-34.67 years), with 31 male patients (55.4%) and 25 female patients (44.6%).

Thirty patients (53.6%) had only BDG, while 26 patients (46.4%) had undergone other procedures before BDG: pulmonary artery banding in 15 patients (26.8%), MBT shunt in 10 patients (17.9%), and both in 1 patient (1.7%). Of the 10 patients who had MBT shunt operations, 7 (70%) had a right MBT shunt, and 3 (30%) had a left MBT shunt. Three patients (5.4%) underwent surgical septectomy with BDG. One patient (1.8%) underwent permanent pacemaker insertion via redo sternotomy.

Five patients (8.9%) underwent percutaneous interventions: Rashkind balloon atrial septostomy after birth and before in 2 patients (3.6%); peripheral pulmonary stenting after BDG in 2 patients (3.6%), and venovenous collateral closure in 1 patient (1.8%).

The median age at BDG was 2.08 (1-3) years (min-max, 0.42-17 years). A total of 47 patients (83.9%) had a right-sided BDG, 8 patients (14.3%) had bilateral BDG, and only 1 patient (1.8%) had a left-sided BDG.

All patients had intact peripheral pulsations, and 54 patients (96.4%) had clubbing. Only 1 patient (1.8%) had SVC syndrome (figure 1 of the supplementary data), and another patient (1.8%) exhibited surface venous collaterals on the chest and abdomen associated with deep cyanosis shortly after BDG (figure 2 of the supplementary data). Both patients underwent surgical intervention to reverse the BDG procedure. Mean baseline SaO₂ was 78.27 ± 8.47%, ranging from 55% to 99%. The hemoglobin indices of the studied patients are presented in Table 1 of the supplementary data.

Table 1. Basic anatomy by transthoracic echocardiography

Figure 1. Aortography in lateral and right anterior oblique cranial views showing 2 major aortopulmonary collateral arteries, one from the right internal mammary artery and the other from the posterior part of aortic arch filling both pulmonary arteries. A, B, successful transcatheter closure of aortopulmonary collaterals. C, D, E, closure of aortopulmonary collaterals by 3 coils. F, final injection after aortopulmonary collateral coil closure.

Figure 2. Successful transcatheter closure of venovenous collaterals. A, venovenous collaterals draining into right and left upper pulmonary veins. B, coil closure of the proximal part of the collaterals. C, D, result after transcatheter closure of venovenous collateral by the coil shows residual sluggish flow to collaterals.

Two of the patients (3.6%) were anemic with hemoglobin levels below the normal range for age and sex (1 girl aged 2 years and 3 months with a hemoglobin level of 8 g/dL, and a 13-year-old boy with a hemoglobin level of 11.8 g/dL). Thirty-eight patients (67.9%) had polycythemia with hemoglobin levels ranging from 14.5 to 21.1 g/dL and a mean of 16.92 ± 1.75 g/dL. Additionally, 31 patients (55.4%) had elevated hemoglobin values ranging from 44.8 to 71, with a mean of 54.37 ± 6.43. Ten patients (17.9%) required venesection before cardiac catheterization. Among them, 4 (7.14%) had venesection for the first time, while the other 6 patients (10.7%) had multiple previous venesections due to symptoms of hyperviscosity (eg, fatigue, headache, dyspnea, and visual disturbances). Echocardiographic data are included in Table 1 and Table 2.

Table 2. Echocardiographic data

A total of 30 patients underwent multislice computed tomography. Of these patients, 2 (6.7%) were found to have aneurysmally dilated BDG (figure 3 of the supplementary data).

Figure 3. Successful transcatheter closure of a venovenous collateral. A, Glenn shunt and venovenous collateral to the left upper pulmonary vein. B, transcatheter closure of the venovenous collateral by 2 coils. C, final injection after closure of the venovenous collateral with significantly diminished flow to the left upper pulmonary vein.

Three patients experienced significant left pulmonary artery stenosis, which was later successfully treated with transcatheter stenting.

All patients underwent cardiac catheterization, which included invasive assessment of pressures and SaO₂ from various cardiac chambers. The results of this assessment can be found in Table 2 of the supplementary data. Venovenous collaterals and APC were comprehensively assessed, and all the data collected are presented in Table 3.

Table 3. Angiographic assessment of collaterals

Among the 56 patients who underwent catheterization, 52 (92.9%) had collaterals, including venovenous and/or APC. Only 4 patients (7.1%) had no collaterals. Of the total, 19 patients (36.5%) were managed with medical treatment and regular follow-up. Another 20 patients (38.5%) were referred for surgical assessment for Fontan completion. Seven patients (13.5%) underwent TCC of collaterals (Table 4 and figure 1, figure 2, and figure 3). Two patients (3.8%) were scheduled for TCC of collaterals in a subsequent session due to financial obstacles. Additionally, 2 patients underwent unsuccessful attempts to close venovenous collaterals (3.8%), 2 patients (3.8%) were referred for revision of the Glenn shunt due to a failed procedure, and 2 patients (3.8%) were referred for revision of the Glenn shunt and biventricular repair.

Table 4. Details of transcatheter closure of collaterals in 6 patients

Three patients developed complications during TCC of collaterals. The first patient experienced complications due to coil embolization in the innominate vein during the attempt to close venovenous collaterals; however, the coil was successfully snared.

The second patient was an 18-year-old woman who underwent elective TCC of a venovenous collateral using an Amplatzer Duct Occluder II (Abbott, United States). After the device was delivered to the collateral, occluding its proximal portion, difficulties arose in separating the device cable. However, after some manipulations and selective injection at the origin of the collateral, localized extravasation was observed at the proximal site. The catheter was retracted to the innominate vein and reinjected after several minutes, revealing decreased extravasation and successful sealing of the perforation. A follow-up chest X-ray showed no further complications (figure 4).

Figure 4. Venovenous collateral angiography in posteroanterior view. A, well-seated Amplatzer Duct Occluder II in venovenous collateral. B, extravasation at the proximal origin of collateral after cable separation. C, injection after several minutes showing sealing of extravasation.

The third patient was a 13-year-old boy who underwent injection of the azygos vein, revealing 2 large right and left venovenous collaterals to the pulmonary veins. Closure of these collaterals was attempted but was unsuccessful. Due to the prolonged procedure, the patient experienced acute left-sided weakness after catheterization. Cerebral magnetic resonance imaging and angiography showed an acute hemorrhagic infarction in the right basal ganglionic and periventricular areas, along with occlusion of the right middle cerebral artery starting from the distal M1 segment, consistent with an embolic event. The patient subsequently underwent mechanical thrombectomy and experienced minimal residual weakness on the left side and dysarthria.

SaO₂ significantly increased after TCC of venovenous collaterals (69.83 ± 10.91 vs 82.83 ± 9.87), with a P value of .008 (Table 5).

Table 5. Comparison between SaO₂ at baseline and after management among patients who underwent transcatheter closure of venovenous collaterals

Basal SO₂ was lower in patients with venovenous collaterals, although this difference was not statistically significant. Hematocrit levels and mean PAP were significantly higher in patients with venovenous collaterals than in those without venovenous collaterals (P = .031 and P = .025, respectively; Table 3 of the supplementary data).

End-diastolic pressure (EDP) was positively correlated with mean PAP with a P value of .001 (figure 4 of the supplementary data).

Age at BDG procedure was positively correlated with aemoglobin (HCT) and aemoglobin levels (P = .001 and P = .002, respectively), with patients who underwent BDG at older ages showing higher hemoglobin and HCT levels.

Length of time since the BDG procedure was negatively correlated with baseline SO₂ (P = .023), with the longer the time since Glenn shunting, the lower the patient’s baseline SO₂. In addition, there was a highly significant positive correlation between the length of time since the Glenn procedure and HCT level (P = .002), indicating that the longer the time since Glenn shunting, the higher the patient’s HCT level.

DISCUSSION

Our patients underwent BDG surgery at a median age of 2.08 [IQR, 1-3] years. We found 3 other recent registries conducted in developing countries similar to ours: Azhar et al.9 in Saudi Arabia, Meyer et al.10 in South Africa, and Tariq et al.11 in Pakistan. The median ages of patients in these registries were 10 months, 2.5 years, and 1.9 years, respectively. In older registries, such as those reported by Talwar et al.12 in India, Al-Dairy et al.13 in Iran, and Sen et al.14 in India, the median ages of patients were 3 years, 5 years, and 7.5 years, respectively, indicating a younger age at BDG in recent registries.9-14 In contrast to registries in developing countries, the Western literature reports a median age at BDG of less than 1 year, as reported by Kogon et al.15 in Atlanta (United States), LaPar et al.16 in Virginia (United States), Reddy et al.17 in California (United States), and Shuler et al.18 in Cincinnati (United States).

Ideally, children should undergo BDG between the ages of 6 and 12 months followed by Fontan completion 1 year later.19 The relatively older age of children undergoing the BDG in developing countries may be due to late presentation, delayed diagnosis, lack of primary health care facilities—especially in rural areas—, lack of timely referral, and families’ reluctance to allow their children to undergo the staged surgical correction for financial reasons.20

Regarding post-BDG interventions, 2 patients (3.6%) underwent peripheral pulmonary artery stenting before presenting to our hospital, and we performed left pulmonary artery stenting in 3 patients (5.4%). In contrast to our study, only 1 patient in the study by Yamada et al. 21 underwent right pulmonary artery stenting. The discrepancy in intervention rates between the 2 studies can be explained by the older age of our patients and efforts to reduce their comorbidities to enhance functional capacity and improve their quality of life, especially since most were not suitable for Fontan completion.

The most common basic anatomy included transposition of the great arteries, double outlet right ventricle, and tricuspid atresia. This finding is consistent with those of Naik et al.22 and Sen et al.1 In contrast, Atz et al.23 studied 382 patients in the United States and found that the most common basic anatomy was HLHS (25.6%), followed by tricuspid atresia (18%) and double inlet left ventricle (13%). The absence of HLHS in registries conducted in developing countries may be attributed to its poor prognosis and low survival rate. Among the 56 patients in our study, 41 (73.2%) had venovenous collaterals. McElhinney et al.24 studied 54 patients, with only 18 (33.3%) having venovenous collaterals. The higher percentage in our study may be due to the longer interval from surgery to catheterization, as the median interval from surgery to catheterization was 1.3 years in McElhinney et al.24 and 7.5 years in our study.

In our study, 37 patients (66.1%) had APC. This percentage is similar to that reported by Triedman et al.,25 who diagnosed APC in 65% of patients.

In our study, 6 patients underwent TCC of venovenous collaterals: 5 patients during this registry and 1 patient in 2019. There was a statistically significant increase in SaO₂ (%) after the procedure (69.83 ± 10.91 vs 82.83 ± 9.87; P = .008). McElhinney et al.24 also reported successful coil embolization of 10 collateral channels in 6 patients, resulting in an increase in SaO₂ of between 9% and 20% (median increase in SaO2 of 16%).

Lu et al.26 reported a cohort study of 9 patients aged 5 to 15 years (median 9 years) with progressive cyanosis after BDG. Successful TCC of the azygos/hemiazygos veins was achieved using coils in 4 patients, patent ductus arteriosus occluders in 3 patients, atrial septal defect occluders in 2 patients, and a patent ductus arteriosus occluder together with coils in 1 patient. Femoral artery SaO₂ increased from 81% to 88%.

In our registry, out of the 6 patients who underwent TCC of venovenous collaterals, only 2 had venovenous collaterals to systemic veins (1 had collaterals to epicardial and abdominal veins, and the other to paravertebral veins), whereas the other 4 patients had venovenous collaterals to pulmonary veins.

We also found that 7 out of 8 patients with a pre-existing bilateral SVC connection developed venovenous collaterals. Additionally, 10 out of 11 patients with inadequate PA distribution/PA distortion and 6 out of 8 patients with impaired ventricular systolic function developed venovenous collaterals. However, these findings were not statistically significant. According to Magee et al.,27 venovenous collateral development was associated with an abnormal superior vena cava connection, pulmonary artery distortion, increased mean SVC pressure, increased mean PA pressure, lower right atrium mean pressure, and an increased mean gradient between the SVC and right atrium. Only the last factor was independently associated with collateral development.

McElhinney et al.24 reported that, in patients who developed venous collateral channels, the mean transpulmonary pressure gradient was higher early the BDG procedure (P = .005). This correlation was no longer significant at follow-up, mostly due to decompression of the SVC system through the venous collateral channels. In our patients, no correlation between transpulmonary pressure gradient (SVC-left atrium) and the presence of venovenous collaterals at follow-up.

In our center, we avoid closure of venovenous collaterals in patients with marked elevation in PAP (pulmonary hypertension) as it is a contraindication; venovenous collaterals decompress the congested venous system. However, in patients with normal PAP, or mean PAP ranging from 14 to 20 mmHg (no pulmonary hypertension, who are nevertheless not good candidates for Fontan completion) plus desaturation, we proceed with venovenous collateral closure.

In the present study, 37 of the 56 patients (66.1%) were found to have APCs. One patient underwent successful TCC of aortopulmonary collaterals. Patients with these collaterals were younger at the time of the Glenn procedure and time since the operation was longer. This finding is consistent with that of Grosse-Wortmann et al.,28 who measured APC blood flow noninvasively in BDG and Fontan patients using MRI. These authors found that a higher Qp/Qs ratio was associated with younger age at the time of CPA and concluded that patients who proceeded to CPA at a younger age were more likely to develop APCs.

We found a highly significant positive correlation between EDP and mean PAP (P value of .001). Consistent with our findings, Schwartz et al.29 reported that, at pre-Fontan catheterization, high mean PAP was associated with high single-ventricle EDP. These authors suggested that this association underscores the significance of EDP in individuals with single-ventricle heart disease. They also noted that EDP plays a major role in determining pulmonary artery and central venous pressures, elevations of which are linked to increased morbidity.

CONCLUSIONS

TCC of collaterals is a technically demanding but effective post-BDG management strategy to improve SaO₂ and quality of life. Awareness of potential complications and their effective management is essential.

FUNDING

None.

ETHICAL CONSIDERATIONS

This study was approved by the research ethics committee of the faculty of medicine of Ain Shams University (FMASU MS 507/2022). Verbal and written informed consent was obtained from participants aged 18 years and older or from the participant’s guardian in patients aged less than 18 years after the aim of the study was explained to them. Our research was carried out in accordance with internationally accepted recommendations for clinical investigation (Declaration of Helsinki of the World Medical Association). Possible sex/gender biases have been considered in the preparation of this article.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence tool was used in the preparation of this article.

AUTHORS’ CONTRIBUTIONS

Y.A. Ali collected data, revised the statistical analysis, and drafted the manuscript. N. El-Sayed Nour El Deen collected data and performed the statistical analysis. G.S. Elshahed supervised data collection, revised the results, and edited the manuscript.

CONFLICTS OF INTEREST

The authors declare that they have no competing interests.

SUPPLEMENTARY DATA

REFERENCES