Author + information
- Received May 11, 2010
- Revision received August 6, 2010
- Accepted August 20, 2010
- Published online December 1, 2010.
- V. Vivian Dimas, MD⁎,
- Cheryl Takao, MD†,
- Frank F. Ing, MD⁎,†,
- Raphael Mattamal, BS⁎,
- Alan W. Nugent, MBBS⁎,
- Ronald G. Grifka, MD⁎,
- Charles E. Mullins, MD⁎ and
- Henri Justino, MD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Henri Justino, Mullins Cardiac Catheterization Laboratories, Texas Children's Hospital, 6621 Fannin, MC 19345-C, Houston, Texas 77030
Objectives We sought to analyze the outcomes of transcatheter patent ductus arteriosus (PDA) occlusion using a variety of devices in infants weighing ≤6 kg.
Background Indications for transcatheter closure of a PDA in infancy include congestive heart failure and/or failure to thrive. Devices available for small infants may be problematic for various reasons, including sheath size, stiffness of delivery system, and anchoring and retrievability characteristics of the device. The Amplatzer Ductal Occluder is approved by U.S. Food and Drug Administration for children weighing >6 kg and older than 6 months of age.
Methods We performed a multicenter, retrospective analysis of children weighing ≤6 kg in whom transcatheter PDA occlusion was attempted between January 1995 and November 2005 at Texas Children's Hospital and January 2001 to November 2005 at Children's Hospital of San Diego.
Results A total of 62 patients underwent attempted closure. The mean age at catheterization was 4.7 ± 2.8 months with a mean weight at catheterization of 4.6 ± 0.9 kg. Successful device placement was achieved in 58 of 62 patients (94%). Among those receiving a device, complete occlusion was noted in all 58 patients at either catheterization or last available follow-up.
Conclusions Percutaneous closure of PDA should be considered even in infants ≤6 kg.
Indications for transcatheter closure of a patent ductus arteriosus (PDA) in infancy include symptoms of congestive heart failure, failure to thrive, and evidence of left ventricular volume overload (1). Devices currently available for transcatheter closure of PDA in the U.S. include coils, the Amplatzer Duct Occluder (ADO), and the Gianturco-Grifka Vascular Occluder Device. When applied in small infants, each of these may be problematic for one or more of the following reasons: relatively large sheath size for small vessels, stiffness of the delivery system with resultant hemodynamic instability during device deployment, risk of protrusion of the device into the aorta or pulmonary artery, poor anchoring or stability within the PDA, and difficult retrievability (2). These devices (e.g., coils), which are used “off label,” do not have specific weight or age recommendations, but the current manufacturer recommendations for the ADO are a weight >6 kg and age >6 months.
Numerous studies have documented the feasibility of catheter-based closure of PDA in older children and adults, however, there is a paucity of data regarding the outcomes of percutaneous closure of PDA in small infants, and in particular, there are no published criteria establishing a minimal weight of 6 kg as a suitable cutoff. We therefore performed a multicenter, retrospective analysis of children weighing ≤6 kg in whom transcatheter PDA occlusion was attempted between January 1995 and November 2005 at Texas Children's Hospital and January 2001 to November 2005 at Children's Hospital of San Diego.
Institutional Review Board approval was obtained at both institutions. A retrospective analysis of children ≤6 kg in whom transcatheter PDA occlusion was attempted between January 1, 1995 and November 1, 2005, at Texas Children's Hospital and between January 1, 2001 and November 1, 2005, at Children's Hospital San Diego was conducted. The cardiology databases at both institutions were searched for eligible patients. The indications for the procedure and any associated congenital heart defects were recorded, as were patient weight, angiographic PDA minimal diameter, occlusion device used, sheath size required, hemodynamic data including Qp/Qs and procedural complications. Angiograms were reviewed in 56 of 62 patients to define ductal morphology and presence of an immediate post-implant residual shunt. Follow-up data including duration of follow-up and the presence of residual shunting noted by echocardiography were recorded.
The variables are presented as a mean ± SD. No statistical comparisons were made, as the data pertain to a single treatment group.
A total of 62 patients were included in the study. Indications for cardiac catheterization included primarily the intention to close the PDA in 52 (48 with congestive heart failure and/or failure to thrive, 3 with left ventricular dilation, and 1 with a residual PDA following surgical ligation). In 10 patients, catheterization was primarily indicated for evaluation of pulmonary vascular resistance (n = 5), and evaluation and potential treatment of other cardiovascular anomalies (n = 5), but PDA occlusion was nonetheless performed at the same procedure. Of the 62 patients included in the study, 30 of 62 (48%) had associated defects (Table 1). Fifteen patients had a restrictive ventricular septal defect (11 in isolation, 4 associated with a small atrial septal defect) and thus did not require surgical closure. One patient with truncus arteriosus had a PDA from the right subclavian artery occluded post-operatively. There was 1 patient with trisomy 21 and atrioventricular canal with severe failure to thrive. The PDA was large and closure was indicated pre-operatively to reduce volume overload and allow for somatic growth. In the patient with interrupted inferior vena cava, a transhepatic approach was used to deliver the ADO.
The mean age at catheterization was 4.7 ± 2.8 months (range 16 days to 1.2 years). The mean weight at catheterization was 4.6 ± 0.9 kg (range 2.5 to 6 kg). The mean angiographic minimal PDA diameter was 2.9 ± 1.1 mm with a range of <1 to 7.3 mm. The mean Qp/Qs ratio (available in 60 of 62 patients) calculated by the Fick method was 3.3 ± 1.8 (range 1 to 10.7) to 1. Classification of ductal morphology as described by Krinchenko et al. (3) was available in 56 of 62 patients: There were 40 patients with type A, 12 with type C, 1 with type D, and 2 with type E ductus morphology. One patient had a PDA arising from the subclavian artery. Angiograms were not available for review in 6 patients and no classification was assigned.
Successful device placement was achieved in 58 of 62 patients (94%), with all 4 unsuccessful cases before the availability of the ADO. There was procedural failure in 3 patients. In 2 of the patients, the attempt at closure was aborted due to the inability to stabilize multiple coils within the PDA using the bioptome technique for delivery, and the patients were referred for surgical closure. In 1 patient, a Gianturco-Grifka Vascular Occluder Device was used to occlude the PDA. During deployment, a portion of the filler wire was extruded from the “sack” upon removal of the pusher wire resulting in a portion of the filler wire protruding in the pulmonary artery. The patient was referred for surgical removal of the device and surgical ligation of the PDA. A single patient weighing 5 kg with a PDA minimal diameter of 4 mm had successful placement of 7 coils, but ultimately required surgical removal of the coils with PDA ligation 3 days following the procedure due to significant residual shunt and hemolysis requiring blood transfusion. Procedural characteristics including type of device used for PDA occlusion, as well as arterial and venous sheath sizes are listed in Table 2. The mean fluoroscopic time was 34 ± 22 min (range 10.5 to 112 min). Complications included right femoral vein trauma in addition to new onset tricuspid insufficiency in 1 patient (weight: 2.5 kg), transfusion of packed red blood cells in 3 patients, referral for surgery in 4 patients (2 due to aborted procedure and 2 due to device malfunction, described above). There were no arterial complications noted at follow-up. No strokes or deaths occurred.
Follow-up data were available in 57 of 58 patients who underwent successful device implantation. The mean follow-up time for the 57 patients was 32 ± 37 months. Immediate residual shunting was present angiographically in 29 of 58 (50%) patients who underwent successful device implantation. No patient had residual shunting at last follow-up by color flow Doppler. Complete echocardiographic data (left pulmonary artery and aortic Doppler interrogation) in addition to evaluation for residual shunting was available for 46 of 57 patients. There was flow acceleration in the descending aorta in 2 patients on follow-up echocardiogram. One patient received a coil (0.038 inches × 5 cm × 4 mm) at a weight of 2.8 kg and was noted to have a peak velocity in the descending aorta of 2.9 m/s at 1-year post-procedure follow-up. The other patient received a 5/4 ADO device at 3.6 kg and had a peak velocity in the descending aorta of 2.3 m/s at 4 months post-procedure follow-up. These 2 patients continue to be followed as outpatients without further intervention. There were 4 patients with flow acceleration noted in the left pulmonary artery. In 1 patient who received multiple coils, there was persistent mild left pulmonary artery stenosis with a peak velocity of 2.6 m/s by Doppler examination 11.8 years after occlusion. The other 3 patients received ADO devices (5/4 device in 2, 10/8 device in 1) had a peak velocity of 2.3 to 2.5 m/s by Doppler examination at an average of 1.9 years follow-up.
Transcatheter closure of PDAs is rapidly becoming the treatment of choice at most centers in larger infants, children, and adults. Since the initial descriptions of PDA closure with Gianturco coils, there have been various techniques for coil delivery reported to achieve greater coil stability during closure (4–6). The most frequent complication using Gianturco coils has been coil embolization in up to 10% of cases (7). Detachable coils were created to address the lack of control during implantation and release of the Gianturco coils, with a decrease in reported embolization rates (7). Despite high success rates for ductal closure with coils, these devices were created for occlusion of other vascular structures and were not made to conform to conical shape of most PDAs (type A). Several devices have been developed specifically for PDA closure. The Nit-Occlud (PFM Medical, Carlsbad, California) coil occlusion system is composed of a stainless steel coil that, once released, assumes a biconical configuration and can be delivered in a controlled fashion. In addition, it can be repositioned or retrieved after delivery if necessary (8). The Nit-Occlud is not currently approved by the U.S. Food Drug Administration (FDA). Currently, the only FDA-approved device for PDA closure is the ADO (AGA Medical Corporation, Plymouth, Minnesota). It is a self-expanding conical device with a single (aortic) retention skirt and is composed of a Nitinol wire mesh with polyester fabric sewn into the mesh to induce thrombosis; it received FDA approval in May 2003. It is available in a wide variety of sizes and is delivered transvenously via a 6- to 8-F sheath as per current manufacturer recommendations. This device is also fully retrievable via its delivery cable before device release (9). A newer generation of the ADO has been developed to contend with the large variation in ductal size and morphology. The ADO II is a fully retrievable device, also made of a Nitinol mesh, possessing a double disc design (an aortic and a pulmonary retention skirt) that articulate with a central plug that is sized to the diameter of the midpoint of the PDA. Different from the currently approved ADO device, there is no fabric sewn into the device. It is a lower profile device suitable for tubular PDAs or complex type D PDAs. It is currently undergoing a prospective clinical trial under an investigational device exemption with conditional FDA approval for 192 subjects at 25 centers. The weight and age restrictions for use of the ADO II are identical to those of the ADO.
Despite current manufacturer recommendations regarding patient age and size, PDAs can be successfully occluded in small infants with few complications, avoiding a thoracotomy and its associated morbidities (10,11). In our experience, 58 of 62 (94%) patients had successful closure of their PDA. Retrospective review of the 4 implant failures revealed favorable ductal morphology for ADO device occlusion. Accordingly, had these patients undergone PDA occlusion after the ADO became available, we believe they would likely have had successful procedures, at least based on their suitable ductal morphology. Our experience suggests that the majority of infants weighing ≤6 kg can undergo PDA device occlusion safely and effectively. We do not generally advocate transcatheter PDA closure in infants weighing <6 kg if the PDA is small and the patient is asymptomatic. Instead, we believe such patients should be monitored and considered for catheter-based closure when they are older and larger. However, symptomatic infants <6 kg with moderate-to-large PDAs pose a therapeutic dilemma. For most infants in this weight range in the current era, percutaneous closure of their PDA will be best achieved using the ADO device because of its transvenous delivery, favorable profile, and easy retrievability. We believe that despite current FDA labeling to the contrary, we demonstrated that the ADO device can be used safely “off label” in infants <6 kg.
Based on our experience, we have generally offered catheter-based closure of PDA as the procedure of choice for symptomatic infants ≥4 kg. Moreover, in carefully selected symptomatic patients with echocardiograms suggesting a suitable conical PDA morphology, PDA occlusion using the ADO in our institution has been performed safely in infants weighing as little as 2.5 kg. Although it is difficult to establish an exact lower weight limit for the safe use of the ADO device (due to the highly variable morphological characteristics of the PDA and adjacent aorta), our current recommendations are as follows: 1) in some symptomatic children weighing 2.5 to 4 kg, consideration should be given to attempting PDA closure using the ADO device if the ductal morphology seems appropriate on echocardiography (i.e., conical in shape and with some area of constriction); and 2) in most children weighing 4 to 6 kg, ADO device closure should be the primary therapy. Because the ADO device can be easily retrieved if PDA closure should prove unsatisfactory (e.g., due to device protrusion), we believe that the risk of attempting PDA closure using the ADO device is overall very low, such that surgical PDA ligation should be considered as a secondary option for patients 2.5 to 6 kg in whom transcatheter closure either fails or is deemed unsuitable.
A limitation of the study was its retrospective nature. Additionally, the study spans a broad era, during which devices available for percutaneous PDA closure varied; hence, a consistent PDA occlusion algorithm was not possible across the study period. Technical advances during this time, most significantly the ADO, were not available to patients in the early part of the study. Lastly, our databases permitted tracking of infants who were referred for cardiac catheterization, and in whom placement of a device within the PDA was attempted. It was logistically impractical to track infants <6 kg who might have had a PDA at catheterization, but in whom percutaneous closure was never attempted. Although we believe that these patients would be very few in number, precise numbers are not available, and our study was limited to reporting those infants in whom a device placement attempt was made.
With the current armamentarium of devices available for PDA closure, the majority of infants weighing 2.5 to 6 kg can safely and successfully undergo PDA occlusion in the catheterization laboratory.
Dr. Justino is a consultant for Daiichi Sankyo Pharma. Drs. Ing and Justino are physician proctors for AGA Medical, Inc. Dr. Mullins is a consultant for NuMed and has stock in Boston Scientific. All other authors report that they have no relationships to disclose.
- Abbreviations and Acronyms
- Amplatzer Ductal Occluder
- U.S. Food and Drug Administration
- patient ductus arteriosus
- Received May 11, 2010.
- Revision received August 6, 2010.
- Accepted August 20, 2010.
- American College of Cardiology Foundation
- Butera G.,
- De Rosa G.,
- Chessa M.,
- Piazza L.,
- Delogu A.,
- Figiola A.,
- Carminati M.,
- et al.
- Krichenko A.,
- Benson L.N.,
- Burrows P.,
- Moes C.A.,
- McLaughlin P.,
- Freedom R.M.
- Schneider D.J.,
- Moore J.W.
- Pass R.H.,
- Hijazi Z.,
- Hsu D.T.,
- Lewis V.,
- Hellenbrand W.E.
- Chorne N.,
- Leonard C.,
- Piecuch R.,
- Clyman R.I.