Transcatheter closure of the patent ductus arteriosus using the new Amplatzer duct occluder: Initial clinical applications in children Basil Thanopoulos, MD, PhD, a Nikolaos Eleftherakis, MD, a Konstantinos Tzannos, MD, b and Christodoulos Stefanadis, MD, PhD b Athens, Greece Background In spite of recent advances in transcatheter management, the occlusion of certain anatomic types of patent ductus arteriosus (PDA), especially in infants and small children, remains a challenge. The aim of the study was to report initial human experience with transcatheter closure of PDA in 25 patients using the new Amplatzer duct occluder (ADO II) (AGA Medical, Golden Valley, MN). Methods The median age of the patients was 3.2 years (range 0.1-5 years), and the median weight was 10.5 kg (range 3-18 kg). The device used is a modified ADO II made of fabric-free fine Nitinol wire net into 2 very-low-profile disks with an articulated connecting waist. Both disks are 6 mm larger than the diameter of the connecting waist. Connecting waist diameters range from 3 to 6 mm. Results The mean PDA diameter was 3.6 ± 1.3 mm (range 0.6-5 mm). The mean device diameter (waist diameter) was 4.3 ± 1.4 mm (range 3-6 mm). Complete echocardiographic closure of the ductus at 1-month follow-up was observed in 24 (96%) of 25 patients. Immediately after the procedure, there was a mild left pulmonary stenosis (Doppler gradient of 15 mm Hg) in 2 of 25 patients. No other complications were observed. Conclusions The ADO II is a promising addition to our armamentarium for PDA closure. Further studies are required to document its efficacy, safety, and long-term results. (Am Heart J 2008;156:917.e1-917.e6.) In spite of the obvious advantages of the percutaneous techniques, device closure of certain anatomical types of patent ductus arteriosus (PDA) as well as the application of the percutaneous techniques in infant and small children has significant limitations. 1 This study reports initial human experience with transcatheter closure of PDA in 25 patients using the new Amplatzer duct occluder (ADO II) (AGA Medical, Golden Valley, MN). Methods Patient population A total of 25 patients from 2 cardiac centers in Greece underwent attempted PDA occlusion with the use of the ADO II. The median patient age was 3.2 years (range 0.1- From the a Department of Cardiology, Aghia Sophia Children's Hospital, Athens, Greece, and b 1st Department of Cardiology, University of Athens, Hippocration Hospital, Athens, Greece. Submitted June 6, 2008; accepted August 3, 2008. Reprint requests: Basil (Vasilios) D. Thanopoulos, MD, PhD, Department of Pediatric Cardiology, Aghia Sophia Children's Hospital, Thivon and Levadias Street, Athens 115 27, Greece. E-mails: thanopoulos.d@gmail.com, vthanop@otenet.gr 0002-8703/$ - see front matter 2008, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2008.08.001 5 years), and the mean weight was 10.5 kg (range 3-18 kg). Seven patients were b4 months of age with a body weight ranging from 3 to 5.5 kg. Fourteen patients had echocardiographic evidence of significant shunt through the PDA with left atrial enlargement and ventricular volume overload. Patients with (1) additional cardiac anomalies that would require cardiac surgery; (2) body weight b3 kg; (3) minimal PDA diameter N5.5 mm; and (4) aortopulmonary window type PDA (absence of tubular part) were excluded from the study. The PDA inthese patients was closed surgically or percutaneously with the use of the standard Amplatzer duct occluder (ADO I). Device and delivery system The ADO II is a modification of the ADO I made of fabric-free (there are no polyester patches) fine Nitinol (NMT Medical, Inc, Boston, MA) wire net into 2 very-lowprofile disks with an articulated connecting waist (Figure 1). Both disks are 6 mm larger than the diameter of the connecting waist and can swivel around the connecting waist adapting at different angles of PDA insertion into the aorta and the pulmonary artery, respectively. Device sizes (connecting waist diameters) range from 3 to 6 mm. The ADO II is available in 2 lengths, 4 and 6 mm, respectively. It is delivered through
917.e2 Thanopoulos et al American Heart Journal November 2008 a 4F to 5F low-profile braided and tapering delivery sheath with flexible distal segment. The ADO II in its current design is not suitable for closure of PDAs N5.5 mm in diameter nor for aortopulmonary window type ductuses. All devices were implanted in the context of a research protocol approved by the Ethical Committees of the participating Hospitals. Informed parental consent was obtained for each patient. Procedure The technique of transcatheter closure of PDA using the ADO II is similar to that described for the ADO I. 2 The device size was selected according to the narrowest diameter of ductus along its length. For ductuses b2.5 mm, an ADO II of 3 mm was used. In patients with larger ductal diameter (up to 5 mm), a device with a waist diameter equal to or up to 1.5 mm larger than the ductus was used. For short (b5 mm) and long (N5 mm) PDAs, an occluder 4 and 6 mm in length was used, respectively. Pull-back pulmonary and aortic pressure tracings as well as a pulmonary arteriogram and descending aortogram were performed after device placement to document residual shunts, and left pulmonary artery or aortic obstruction. Once optimal position was confirmed, the devices were released by counterclockwise rotation of the delivery cable. Two-dimensional color Doppler echocardiography and descending aortography were performed after the release of the device to check for residual shunts and left pulmonary artery and/or descending aorta obstruction. All patients were discharged 24 hours after the procedure on no medication. A chest radiograph and complete 2-dimensional and color Doppler echocardiographic studies were performed on all patients at 24 hours and 1 month after the procedure. Special attention was paid to residual ductal flow and left pulmonary artery or descending aorta stenosis. Statistical analysis Results are expressed as mean value ± SD, with confidence intervals given where applicable. Results According to the alphanumeric classification proposed by Krichenko et al, 3 15 patients had a PDA type A (conical ductus with ampulla at the aortic end), 4 had PDA type E (elongated PDA with constriction at the pulmonary end), 2 had PDA type B (short PDA with no constriction), 2 had PDA type C (tubular ductus), and 2 had PDA type D (PDA with constrictions at both ends). Delivery of the device was successful in all patients. In 2 patients with small PDAs, types D and E (0.6 and 0.8 mm, respectively), and oblique pulmonary insertion, the ductus could not be crossed from the pulmonary artery. It should be noted that in one of these cases, the ductus (0.6 mm type D PDA; Figure 2) could not be crossed from the aorta by a 4F Figure 1 Side view of the ADO II made of fine fabric-free Nitinol wire mesh. Microvena catheter in preparation for coil insertion. In both patients, the ADO II was successfully implanted using a femoral artery approach using a 4F delivery sheath. The mean PDA minimal diameter determined by aortography was 3.6 ± 1.3 mm (range 0.6-5 mm). The mean device diameter was 4.3 ± 1.4 mm (range 3-6 mm). In 1 patient, a 1-month-old infant (body weight 3.2 kg) with a type A PDA measuring 4 mm in diameter and 5 mm in length, deployment of an ADO II 5-6 mm (size and length, respectively) resulted in significant left pulmonary artery and aortic obstruction. Therefore, the occluder was repositioned within the sheath, and the ductus was closed successfully with no complications using a 4-4 mm ADO II (Figure 3). Complete angiographic closure was observed in 21 of the 25 patients (Figure 4). In 4 patients, there was a trivial residual shunt after the procedure. Immediately after the procedure, there was a mild left pulmonary stenosis (Doppler gradient of 15 mm Hg) in 2 infants with type A PDA ( 2 months old, body weight 3.5 and 4 kg, respectively) after the implantation of an ADO II, 4-4 mm and 5-4 mm, respectively. No obstruction of the left pulmonary artery or the descending aorta was noted in the remaining patients. There were 2 temporary losses of the arterial pulse and 2 minor assorted procedural complications. No other complications were observed. Follow-up Follow-up data were available in all 25 patients at 24 hours and 1 month after the procedure. At 1 month,
American Heart Journal Volume 156, Number 5 Thanopoulos et al 917.e3 Figure 2 Steps of transcatheter closure using the ADO II in a 4-year-old patient with a type D PDA. (A) Selective injection of contrast medium in the aortic mouth of the ductus showing a small type D PDA with 0.6-mm minimal diameter. (B) Crossing of the PDA using a 0.014-in. coronary guidewire. (C) Deployment of the left disk of a 3-4 mm ADO II in the main pulmonary artery. (D) Descending aortogram in the lateral projection after the release of the ADO II revealing complete occlusion and good device position. color Doppler flow mapping revealed complete closure in 24 (96%) of the 25 patients (Figure 5). In 2 patients, a device-related mild left pulmonary artery stenosis remained unchanged. There was no evidence of device migration, thromboembolism, endocarditis, or hemolysis in any of the patients. Discussion None of the currently available devices, including the ADO I, is ideal for closure of moderate to large PDAs in infants and small children. This is due to the risk of protrusion of the device into the descending aorta or the pulmonary artery, causing significant hemodynamic compromise. The PDA as a remnant of the sixth aortic arch forms an acute, usually 30, angle with the aorta. Because the retention disk of the ADO is at right angle (90 ), it may protrude into the aorta causing obstruction in small pediatric patients and in patients with certain anatomical types of PDA with a small or absent ampulla. 2 Toavoidprotrusionoftheaorticretentiondiskinto the descending aorta and to facilitate catheter closure of PDAs with insufficient ampulla, AGA Medical introduced a variety of prototype modified Amplatzer duct occluders. The angled Amplatzer duct occluder 4 and the swivel disk device were designed to decrease the possibility of encroachment to the aorta in type A PDAs; whereas, the plug occluder and the vascular plug were especially made for closure of types C, D, and E PDAs. However, because of their design (increased stiffness and large size of the delivery system), none of these investigational devices are appropriate for closure of small ( 1 mm) PDAs as well as of moderate to large ductuses in small infants 4 (swivel disk device and plug occluder, personal data). In addition, the use of the vascular plug because of lack of Dacron patches and retention disk has been associated with large residual
917.e4 Thanopoulos et al American Heart Journal November 2008 Figure 3 Antegrade descending aortogram in the lateral projection (A) obtained from a 1-month-old (body weight 3.2 kg) showing a large, 4-mm-diameter type A PDA. (B) Pulmonary artery arteriogram and antegrade left ventriculography (C) in the lateral projection before release of a 5-6 mm ADO II revealing significant device-related left pulmonary artery and aortic obstruction, respectively. (D) Retrograde lateral aortogram after implantation of an ADO II 4-4 mm demonstrating complete closure and good device position with no device-related aortic obstruction. shunting requiring surgical intervention or additional implantation of multiple coils. 5 The ADO II was manufactured to overcome the drawbacks of the ADO I and its modifications for catheter closure of PDA. When compared to other Amplatzer PDA occluders, the most important property of the ADO II is the very-low-profile disks, which can swivel around the articulations of the connecting waist and adapt at different angles of PDA insertion into the aorta and the pulmonary artery, minimizing the risk of device-related obstruction. In addition, due to the absence of Dacron patches and its low profile 4F to 5F delivery sheath with flexible distal segment, the ADO II can be implanted in small infants and very small PDAs as an alternative to coil implantation. Two small infants with moderate to large PDAs in our study developed device-related mild left pulmonary artery (LPA) stenosis as a result of interference of the right disk with the pulmonary blood flow. Although this type of partial obstruction is expected to disappear with the growth of the pulmonary arteries, 6 long-term follow-up of these patients is of paramount importance. In addition, a larger patient population is necessary to estimate the incidence of LPA stenosis in small infants after PDA closure using the ADO II. Our findings with the use of the ADO II suggest that this occluder is a promising device for catheter closure of most anatomical types of small and moderate to large PDAs in small as well as in large pediatric patients. Device implantation was successful in all patients including 7 infants, 1 to 3 months old, with large PDAs (3.5-4.2 mm). All but 2 patients had complete closure without significant complications during the procedure or at a short-term follow-up. It should be noted, however, that the ADO II in its current design is not suitable for closure of PDAs N5.5 mm and window -type ductuses. In addition, its use in very small infants (b5 kg) with large PDAs ( 4 mm) and absent or small ductal ampulla still
American Heart Journal Volume 156, Number 5 Thanopoulos et al 917.e5 Figure 4 Successful closure of types A (A, B), D (C, D), and E (E, F) PDAs in 3 patients (9 months, 2 and 3 years old, respectively) using the ADO II. carries the risk of protrusion of its, relatively large for these patients, retention disks causing obstruction of the left pulmonary artery and the aorta. Based on our preliminary experience, we believe that ADO II with smaller retention disks would achieve successful PDA closure and decrease the risk of device-related obstruction in small infants with moderate to large PDAs. Study limitations Our study has some limitations. The main limitation is that the number of small infants who might benefit from the new ADO is limited. Another limitation is the lack of a comparative group treated with the ADO I. Nevertheless, based on our previous experience, 2,7 we can say that the ADO II seems to be a more suitable device than ADO I for catheter closure of a wide range of anatomical types of PDA up to 5.5 mm, particularly in small pediatric patients. Conclusions The ADO II is a promising addition to our armamentarium for PDA closure. However, further studies are
917.e6 Thanopoulos et al American Heart Journal November 2008 Figure 5 Antegrade descending aortogram in the lateral projection (A) obtained from a 3-month-old (body weight 3.5 kg) showing a large, 4.2-mmdiameter type C PDA. Repeat retrograde aortogram (B) after placement of a 5-mm ADO II showing good position of the occluder and a small residual shunt through the right disk of the device. Transthoracic 2-dimensional (C) and color Doppler images (D) obtained from suprasternal longaxis and parasternal short-axis, respectively, 1 month after the implantation the ADO II revealing complete closure, good device position (arrows) with no evidence of aortic obstruction. required to document its efficacy, safety, and long-term results in a larger patient population. References 1. Krasuski RA. Patent ductus arteriosus closure. J Interv Cardiol 2006;19: S60-6. 2. Thanopoulos BD, Hakim FA, Hiari A, et al. Patent ductus arteriosus equipment and technique. Amplatzer duct occluder: intermediate-term follow-up and technical considerations. J Interv Cardiol 2001;14: 247-54. 3. Krichenko A, Benson LN, Burrows P, et al. Angiographic classification of the isolated, persistently patent ductus arteriosus and implications for percutaneous catheter occlusion. Am J Cardiol 1989;67:877-80. 4. Masura J, Gavora P, Podnar T. Transcatheter occlusion of patent ductus arteriosus using a new angled Amplatzer duct occluder: initial clinical experience. Cathet Cardiovasc Interv 2003;58:261-7. 5. Javois AJ, Husayni TS, Thoele D, et al. Inadvertent stenting of patent ductus arteriosus with Amplatzer vascular plug. Cathet Cardiovasc Interv 2006;67:485-9. 6. Carey LM, Vermillon RP, Shim D, et al. Pulmonary artery size and flow disturbances after patent ductus arteriosus occlusion. Am J Cardiol 1996;78:1307-10. 7. Thanopoulos BD, Rigby ML, Trapali Ch, et al. Outcome of transcatheter closure of patent ductus arteriosus in children using the Amplatzer duct occluder. Cardiol Young 2007;17(Suppl):70 (abstract).