Percutaneous Closure of Medium and Large PDAs Using Amplatzer Duct Occluder (ADO) I and II in Infants: Safety and Efficacy

Abstract: Background. The use of the Amplatzer duct occluder (ADO; AGA Medical Corporation) is well established and reported in children and adults, but there are only occasional reports on use in symptomatic infants. Methods and Results. Between March 2009 and January 2011, a group of 47 infants less than 2 years of age with symptomatic patent ductus arteriosus (PDA) was treated using ADO I and II devices. Patients were divided into infants less than 1 year old (group A; n = 28/47; 59.6%) and children between 1 and 2 years old (group B; n = 19/47; 40.4%). Physical examinations and echocardiograms were performed before the procedure and at follow-up (3, 6, and 12 months). Mean age was 5.3 ± 2.3 months for group A and 12.6 ± 1.7 months for group B. Mean weight at closure was 4.8 ± 1.9 kg for group A and 7.3 ± 2.1 kg for group B. ADO I was deployed in 19/28 of group A (67.9%) and 16/19 of group B (84.2%). ADO II was used in 9/28 of group A (32.1%) and 3/19 of group B (15.8%). No residual shunt at the end of the procedure was detected by angiography in any of the cases closed with ADO I and only 3/12 (25%) closed with ADO II showed a minimal residual flow. No mortality or major complications occurred. Six months after closure, weight gain, control of respiratory infections, and regression of left ventricular dilatation with improved systolic function were observed. Conclusions. Percutaneous closure of moderate to large PDAs using ADO I and II devices in infants and children younger than 2 years of age is safe and effective.

J INVASIVE CARDIOL 2012(11);24:579-582

Key words: Amplatzer duct occluder, patent ductus arteriosus

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Percutaneous closure of patent ductus arteriosus (PDA) is a well-established procedure for the vast majority of pediatric patients. Since the first percutaneous closure of PDA by Porstmann,^1,2 various researchers have described several techniques and occluders for non-surgical closure.^3-7
The degree of successful deployment is variable and the incidence of residual shunting is reported to be between 3% and 38%.^1-9 In 1998, Masura et al¹⁰ published the first series of cases of percutaneous closure of the arterial duct using the new Amplatzer device, which was especially designed for medium to large ducts. The Amplatzer duct occluder (ADO; AGA Medical Corporation) has been widely used in many centers, with less incidence of residual leak, embolization, and left pulmonary artery stenosis.^11,12 An important advantage is that it has a small-caliber detachment system, and so can be used in young children. Some difficulties in using the ADO for occlusion of a large ductus in infants have been reported^13,14 and few studies have investigated their usefulness in children under 1 year of age. In this study, we describe our experience, immediate and mid-term results with the use of the ADO to close moderate to large PDAs in a pediatric population of infants and children <2 years of age.

Methods

Between March 2009 and January 2011, a cohort of 47 infants and children less than 2 years of age with PDAs were percutaneously closed using ADO I and II devices. Patients were divided into infants less than 1 year (group A; n = 28/47; 59.6%) and children between 1 and 2 years (group B; n = 19/47; 40.4%). The mean ductal size was 3.8 ± 2.4 mm as estimated echocardiographically. Both groups suffered congestive heart failure, moderate to severe left ventricular (LV) dilatation and compromise of LV systolic function. Failure to thrive and recurrent bronchopneumonias were prominent features in the entire study group.

All patients underwent clinical evaluation, chest x-ray and echocardiography upon admission. The left ventricular end-diastolic dimension (LVEDD), left atrial diameter (LAD), estimated systolic pulmonary artery pressure (ESPAP), and LV fractional shortening (FS%) were assessed using detailed transthoracic echocardiography (TTE) including 2-dimensional (2D), M-mode, and Doppler assessments. Ductal size, morphology, and transductal pressure gradient were evaluated. Informed consent was obtained from the parents of each patient.

The selection criteria were as follows: age ≤2 years, weight >3.5 kg, and clinical and echocardiographic findings of PDA with a minimum diameter of ≥2 mm. The clinical indications for PDA closure were as follows: heart failure, failure to thrive, recurrent respiratory infections, and dilatation of the left side as evaluated by 2D echocardiogram. Recurrent respiratory infections were defined as more than 6 events during a 6 month period and failure to thrive was defined according to Ramos-Galvan,¹⁵ as a child younger than 2 years whose weight crosses two major percentiles downward in a standardized growth grid using the 90th, 75th, 50th, 25th, 10th, and 5th percentiles as the major percentiles. All patients had signs of significant left to right shunting through the PDA with left atrial enlargement and ventricular volume overload on 2D echocardiography.
The form of the arterial duct was determined according to the classification of Krichenko.¹⁶

Device selection and implantation protocol. The ADO implantation protocol has been described in previous communications.^10,17-19 The procedure was conducted under general anesthesia, with biplane fluoroscopy. The femoral artery and vein were catheterized and 100 U/kg sodium heparin and cefotaxime 100 mg/kg single dose were administered. After recording pulmonary and systemic pressures, an aortogram was conducted in lateral and right anterior oblique projections to define duct morphology and size. The largest and smallest diameters of the ductus were measured (the larger measurement being at the aortic side and the smaller being at the pulmonary side); the diameter of the aortic ampulla and the length of the PDA were also recorded.

Anterograde catheterization was performed in all cases. Devices at least 1-2 mm larger than the minimum diameter of the PDA were selected. Generally, a 5-6 Fr AGA sheath (AGA Medical Corporation) was used to deliver the device. The device, which when attached to the tip of the release cable and withdrawn into the loader, was introduced through the sheath to the descending aorta. Once in place, the retention disk was opened and positioned in the aortic ampulla of the duct.

Subsequently, the rest of the sheath was withdrawn toward the pulmonary trunk, positioning the tubular part of the Amplatzer device within the duct. With the device still anchored to the release cable, an aortogram was performed and when good placement was verified, the device was detached; 10 minutes after ADO implantation, angiography of the descending aorta was conducted to detect any residual shunt.

The ADO I is a cone-shaped device, 7 mm in length, made of a 0.004˝ nitinol wire mesh. A 2 mm retention skirt extends radially around the distal part of the device, assuring secure fixation in the mouth of the PDA. Prostheses are available in sizes ranging from 6-4 to 14-12 mm at increments of 2 mm. The device is attached by a recessed micro-screw to a 0.038˝ delivery cable made of stainless steel; it is delivered through a 5 to 6 Fr long sheath. For introduction into the delivery sheath, the device is pulled into a special Teflon loader.

The ADO II differs in being composed of two discs and a connecting waist. It is available in waist sizes (3, 4, 5, and 6) in two lengths for each size (4 and 6 mm).

Following the procedure, 3 doses of antibiotics were given. Patients were discharged the next day after clinical evaluation. Prophylaxis for bacterial endocarditis was indicated for 6 months following the procedure.¹⁶

Follow-up protocol. Chest x-ray and TTE were conducted at 24 hours to evaluate the shape and position of the device. Color Doppler ultrasound was used to detect and quantify any residual shunt.
The severity of leakage as assessed by color Doppler was arbitrarily defined as follows:18 trivial, <1 mm diameter; mild, 1-2 mm diameter; or moderate, >2 mm diameter at the site of leak onset. Pulsed and continuous-wave Doppler ultrasound were used to determine flow and velocity patterns in the descending aorta and pulmonary artery to rule out obstruction. Follow-up with TTE was conducted at 1, 3, 6, and 12 months after implantation. Major and minor complications related to device implantation were analyzed and described at each assessment. Major complications included: procedure-associated mortality; femoral artery lesion; blood loss ≥5% of the estimated blood volume; migration of the device to the lumen of the pulmonary branch or descending aorta. Minor complications included protrusion of the device into the bed of the pulmonary branch or descending aorta causing turbulent flow (≥2-2.5 m/s) across the origin of the left pulmonary artery or descending aorta, and was considered to be acquired stenosis.

Statistical analysis. Continuous variables were expressed as mean ± standard deviation or as medians and intervals; discrete variables are expressed as absolute values and percentages. The Student’s t-test was used to compare continuous variables, and the Fisher’s exact test was used for comparison of discrete variables. P-value less than .05 was considered significant.

Results

The study included 31 girls (66%) and 16 boys (34%). Their mean age was 5.3 ± 2.3 months for group A and 12.6 ± 1.7 months for group B. Mean weight at closure was 4.8 ± 1.3 kg for group A and 7.3 ± 2.1 kg for group B.

A total of 44/47 of the study group (93.6%) had symptoms of heart failure and failure to thrive, of whom 33/43 (77%) had cardiomegaly on chest radiography and echocardiography and 21/47 (44.7%) had recurrent respiratory tract infections. Three (6.4%) were asymptomatic, all in group B. PDA presented as an isolated lesion in 41/47 of patients (87%), where a patent foramen ovale was not included in the definition of associated lesions. Associated heart lesions were seen in 6/47 (13%): 4 cases of moderate to severe valvular pulmonary stenosis, and 2 cases of associated complete heart block (Table 1).

On reviewing the TTE data of all cases, the mean ductal size was 3.8 ± 2.4 mm for group A and 4.2 ± 1.9 mm for group B. Mean LVEDD was 32.4 ± 4.7 mm and 36.3 ± 4.9 mm for groups A and B, respectively. Most of the patients had Doppler evidence of pulmonary hypertension with a mean ESPAP of 57.2 ± 6.6 mm Hg for Group A and 54.9 ±7.3 mm Hg for group B. Comparing these data between the two groups revealed no statistically significant differences (P>.05). Data illustrated in Table 2.

The minimum and maximum diameters of the arterial duct, measured angiographically, were 3.7 ±1.1 mm and 8.8 ± 1.9 mm for group A and 4.2 ± 0.9 mm and 10.2 ± 2.4 mm for group B, respectively. Device implantation was successful in all 47 patients (100%). The duct morphologies according to the Krichenko classification16 were as follows: type A in 44/47 patients (94%); type B in 1 patient (2%); and type C in 2 patients (4%).

Pulmonary hypertension was observed in all patients. The mean procedure time was 59 ± 3.7 minutes and 61.3 ± 7.4 minutes for groups A and B, respectively, with no significant differences between them. ADO I was deployed in 19/28 group A patients (67.9%) and 16/19 group B patients (84.2%). The sizes of the implanted devices were as follows: 5/4 in 1 patient; 6/4 in 18 patients; 8/6 in 14 patients; and 10/8 in 2 patients. ADO II was used in 9/28 group A patients (32.1%) and 3/19 group B patients (15.8%). ADO II size 5/4 mm was used in 9 cases and 5/6 mm in 3 cases. No residual shunt at the end of procedure was detected by angiography in any of the cases closed with ADO I. A total of 3/12 cases (25%) closed with ADO II revealed minimal intraprosthetic flow that disappeared at 1-month follow-up (Table 1).

There was no procedure-associated mortality. Immediate occlusion, confirmed by angiography, was achieved in 44/47 patients (93.6%); 3/47 patients (6.4%) showed trivial postprocedural intraprosthetic leak. After device implantation, no patient showed a pressure gradient between the ascending and descending aorta, or between the left pulmonary artery and pulmonary trunk.
During the procedure and at the endpoint of the study, no major complications occurred. Minor complications occurred in 4/28 patients (14.3%) in group A and 2/19 patients (10.5%) in group B, in the form of peripheral vascular complications such as loin hematoma and venous thrombosis which were managed successfully with no long-term sequelae. A total of 2/47 cases (4.3%) had mild LPA stenosis with a Doppler systolic gradient of 16 mm Hg in 1 case and 19 mm Hg in the other. One/47 cases (2%) had intra-aortic bulge of the device, with no associated systolic gradient across the descending aorta. These 3 cases were in group A, less than 6 months of age and <5 kg in weight.

At 6- and 12-month follow-up after closure, weight gain, control of respiratory infections, and regression of LV dilatation with normalization of the systolic function were observed. The echocardiographic data and weight before and at 6-month follow-up are shown in Table 2.

Discussion

In this study, the results of using the ADO for the percutaneous closure of PDA in children under 2 years of age are presented. The immediate occlusion rate was 93.6% and 6.4% had trivial residual leak that disappeared after 1 month. Occlusion rate was 100% when using an ADO I device and 88% when ADO II was used, as a residual shunt was observed in 3/12 cases (12%) and disappeared at 1-month follow-up. An occlusion rate of 96% was obtained at 3-month follow-up in many studies.^10-12,15-18

There are few studies on the use of ADO in children under 1 year of age or weighing ≤10 kg.^11,16,19-21 The mean age and weight in our study group was 5.3 months and 4.8 kg for group A and 12.6 months and 7.3 kg for group B. The improvements made to the Amplatzer occluder — taking into account the small size of the release systems (5-7 Fr) and the conic shape of the prosthesis — facilitate their use in relatively large ducts in low-weight, premature babies under 1 year of age.^19-21,22 Previous studies have recommended that the ADO should not be used in patients weighing <5 kg due to observed technical difficulties,^11,17,20 which may still be observed in infants weighing ≥5 kg.20 In this study, we encountered no technical difficulties with implantation, probably because 94% of our study population had Krichenko type A duct morphology.

PDA may be an isolated anomaly or associated with some other cardiac anomalies.21,22 In this study, 6/47 cases (13%) had an associated cardiac anomaly: 4 cases of moderate to severe valvular pulmonary stenosis, and 2 cases of associated complete heart block. Infants with a large ductus are usually symptomatic with tachypnea, tachycardia, and difficulty in feeding. Failure to thrive and recurrent respiratory tract infections are also quite common. Early closure is generally required to relieve the symptoms. Recurrent chest infections were documented in 44.7% of cases. A total of 93.6% of our cases had symptoms of heart failure and failure to thrive and were receiving antifailure medications such as digoxin, captopril, and frusemide, which were the basis for the early duct closure.

Procedure failure has been reported in many studies.^10,13 Fischer et al¹³ mentioned technical difficulties in 9 out of 12 patients. In this study, we had no device implantation failures.
Although coil closure is effective, procedural failure is not uncommon in infants with a large ductus, and using large and multiple coils in infants frequently results in left pulmonary artery stenosis.^2,5-7,9,23 Left pulmonary artery stenosis is not uncommon following deployment of ADO, but is usually mild (Vmax <2.5 m/s).^10-14 Avoiding using an excessively over-sized device in infants may decrease the incidence of this complication. Coarctation of the aorta following implantation of an ADO is not rare,^10-12,24 but occurs mostly in young infants, in whom an excessively oversized device is implanted, resulting in protrusion of the retention flange into the aorta. None of the patients above the age of 1 year showed these complications. However, in the patients <1 year, mild LPA stenosis was noted in 2 patients and intra-aortic bulge was noted in 1 patient. ADO I was deployed for closure in these 3 cases; on the other hand, no similar findings were encountered in any of the cases where ADO II was deployed.

Moreover, all these patients were <6 months and 5 kg, hence presuming a link to low body weight since these complications are observed with greater frequency in infants and young children with low body weight, an effect related to small vessel calibers and relatively large delivery sheaths.^19,20,22 In most patients, aortic obstruction is clinically non-significant and is only detected by echocardiographic study,²⁴ as is the case in the present work.

None of our patients died. Procedure-related mortality is generally rare (12 and only immediate deaths have been reported).^11,12,21-27 Procedure-associated complications have been described in the different age groups, and these are relatively major in patients <1 year of age or weighing <10 kg.^19-21 No major complications were encountered in any of our study group. Faella et al¹² report an 8.2% incidence of complications in children aged 1 year or less, compared to an incidence of 3.8% among older children. Butera et al14 observed minor complications in 3 patients under 1 year of age in a series of 18 symptomatic children under 3 years of age, all of whom had undergone successful closure of PDA. Concordantly, the overall incidence of complications observed in our study was (12.8%), 4/28 patients (14.3%) in group A and 2/19 patients (10.5%) in group B, and all were minor in the form of mild loin hematoma in 5 cases in which a 6 Fr delivery sheath had been used and 1 case of venous thrombosis treated with urokinase. These were managed successfully with no long-term sequelae.

Embolization or poor positioning of the device are rare.^11,19,21 High-velocity residual leaks are also rare, which means that mechanical hemolysis is infrequent.^25,26 Thrombus formation or the development of infective endocarditis have not been reported, although the administration of aspirin (5 mg/kg) and antibiotic prophylaxis was recommended for 6 months.¹⁷

When comparing the advantages of the new ADO II with other Amplatzer occluders, Thanopoulos et al²⁷ reported that its most important features were the low-profile retention disks that can adapt to the different PDA insertion angles within the aorta and left pulmonary artery, thereby minimizing the risk of device-associated obstruction.

Conclusion

In this study, we conclude that percutaneous closure of moderate to large PDAs using ADO I and II devices in infants and children younger than 2 years of age is safe and effective as evidenced by the low incidence of complications and residual shunt. Duct morphology, proper device selection, and masterful technique are mainstays for success.

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From the Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted March 13, 2012, provisional acceptance given March 27, 2012, final version accepted May 4, 2012.
Address of correspondence: Ranya A Hegazy, MD, Assistant Professor of Pediatrics, Faculty of Medicine, Cairo University, 3 Ramez St. off Shehab St, Mohandeseen, Giza, Egypt. Email: r_hegazy@hotmail.com