contemporary management of children with atrial septal defects

Contemporary Management of Childrenwith Atrial Septal DefectsA Focus on Transcatheter Closure

Rolf G. Bennhagen,1 Peter McLaughlin2 and Lee N. Benson1

1 The Divisions of Cardiology, The Hospital for Sick Children, The Toronto General Hospital, The University of Toronto School ofMedicine, Toronto, Ontario, Canada

2 The University Health Network, The Toronto General Hospital, The University of Toronto School of Medicine, Toronto,Ontario, Canada

Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4451. Surgical Correction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4462. Devices for Interventional Closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446

2.1 The CardioSEALΤΜ Device . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4462.2 The STARFlexΤΜ Device . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447

3. Patient Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4474. Device Implantation Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448

4.1 Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4484.2 Estimating the Size of the Defect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4484.3 Loading the Device . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4494.4 Device Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4494.5 Release of Device, After Release and Retrievability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4494.6 Practical Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449

5. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4505.1 Immediate Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450

5.1.1 CardioSEALΤΜ and STARFlexΤΜ Devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4505.1.2 Amplatzer® Septal Occluder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4505.1.3 Das-Angel Wings ΤΜ Device . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4515.1.4 ASDOS DeviceΤΜ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4515.1.5 Buttoned DeviceΤΜ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4515.1.6 HELEX Septal Occluder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451

5.2 Healing Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4515.3 Adverse Events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451

6. Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4517. Discussion and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452

Abstract Atrial septal defects that result in right atrial and ventricular volume overload should be closed ifdiagnosed in children and adolescents. With closure of the atrial septal defect, the left-to-right shunt iseliminated e.g. the volume loading of the right heart, the excessive pulmonary blood flow and the totalcardiac work load are reduced. The possibility of future arrhythmic events is lessened and paradoxicalemboli across the septum eliminated. The first intracardiac surgical repair of a congenital lesion was adefect in the atrial septum nearly 50 years ago. Surgical closure remains a valuable, although viable tech-nique. Recently percutaneous transcatheter techniques are now available. The conventional approach isvia a median sternotomy incision but is associated with pain, risk of wound infection, postoperative im-mobilization and a permanent scar. It has been suggested that alternative approaches such as surgical repairusing mini-sternotomy or lateral thoracotomy incisions yield similar results to the conventional surgicaltechnique and are associated with fewer adverse effects. Transcatheter closure has developed over the lasttwo decades and has evolved into a well tolerated, efficient and cost effective method with minimal dis-

REVIEW ARTICLE Am J Cardiovasc Drugs 2001; 1 (6): 445-4531175-3277/01/0006-0445/$22.00/0

© Adis International Limited. All rights reserved.

Atrial septal defects are relatively common cardiac lesions,accounting for between 5 and 15% of all congenital heart le-sions.[1-4] Hemodynamically significant atrial septal defects thatresult in volume loading of the right heart should undergo electiveclosure. Recent studies suggest that intervention in the pediatricage group will result in normalization of right heart function andexercise tolerance.[5] It has been generally accepted that a pulmo-nary- to-systemic flow ratio of 1.5:1 or greater[4] was indicativeof intervention although contemporary pediatric cardiovascularassessment would rely upon the presence of right ventricularchamber enlargement and paradoxical interventricular septal mo-tion as indication for closure without-flow calculations. A varietyof anatomical defects in the primum and secundum atrial septumexist and the latter includes the oval fossa defect, the superior andinferior sinus venosus defects and defects involving the coronarysinus.[4] However, the secundum defect is by far the most frequentand uniquely situated for percutaneous closure[6] and will be thefocus of this review.

1. Surgical Correction

Surgical closure of the atrial septal defect was the first intra-cardiac lesion routinely closed, first by deep hypothermia in the1950’s and then using cardiopulmonary bypass. It is today, a welltolerated, low morbidity operation that can be accomplished with,in the pediatric age group, a 3 to 5 day hospital stay. In the era oftranscatheter closure, it is still a viable technique in the symptom-atic small infant, or the defect is found not suitable for deviceimplantation.

Surgical correction, requiring cardiopulmonary bypass andcardioplegia is successful in achieving complete occlusion inmost patients. Surgery carries a near zero risk of mortality[7] andlow morbidity, including pericardial and pleural effusions, ar-rhythmias, postoperative bleeding, atelectasis, pneumonia andsepticemia with or without renal failure.[6,8]

Corrective, operative closure of atrial septal defects is indi-cated for the hemodynamically significant lesion. The standardprocedure is through a median sternotomy incision. If the defectis small, direct suture technique is the preferable method. A patchrepair is required in large defects when the atrial wall cannot beapposed or because of the friability of the surrounding tissues.Different patch materials, such as PTFE (polytetrafluoroethylene,Gore-Tex, Flagstaff, AZ), knitted DacronΤΜ velour or autologouspericardium, can be used. The period of global myocardial isch-emia on bypass is usually less than 30 minutes.

Since sternotomy is associated with pain, the risk of a woundinfection, postoperative immobilization and a permanent surgical

scar, a mini-sternotomy exposure has recently been advo-cated,[9,10] and is becoming the standard in pediatric practice par-ticularly in patients with isolated uncomplicated lesions. It re-quires only a 5cm skin incision but the cardiopulmonary bypasstechnique remains the same as that for a full sternal exposure. Alateral thoracotomy incision has recently been reported and com-pared with conventional median sternotomy and percutaneoustranscatheter techniques[11] in a pediatric population (median age5.8 years, median bodyweight 22.1kg). The overall complicationrate for the three groups was 12.6%, 12.0% and 3.8%, respec-tively, and the mean hospital stay 2.8 ± 1.0 days, 6.5 ± 2.1 daysand 2.1 ± 0.5 days, respectively. The main divider still being theneed for extracorporeal circulation and cross-clamping of theaorta with the two surgical methods. The authors conclude thethree methods to be equally effective but the percutaneous andthe minimally invasive surgical methods are superior from a cos-metic, financial and organizational point of view.

2. Devices for Interventional Closure

As interventional procedures evolved in other branches ofmedicine, it was a natural that an a nonsurgical technique fordefect closure would be developed.[12-16] Two such cardiac im-plants are the CardioSEALΤΜ1 (CardioSEALΤΜ Septal OcclusionSystem) and the STARFlexΤΜ (CardioSEALΤΜ Septal Occluderimplant with STARFlexΤΜ Centering System) septal occludersmanufactured by NMT Medical, Inc., Boston, MA. While underinvestigational use in the US, the CardioSEAL™ device is ap-proved under the Humanitarian Device Exemption Act in the US.A number of devices are in general use or being investigated inclinical trials (see section 5.1). The authors have extensive expe-rience with the use of the CardioSEALΤΜ and STARFlexΤΜ de-vices and, therefore, application of the CardioSEALΤΜ devicewill serve as a model for other devices in this review.

2.1 The CardioSEALΤΜ Device

The first version of this double-disc occluder was the earlierBard ClamshellΤΜ Septal Umbrella (CR Bard, Inc., Billerica,MA, USA) which appeared in 1989. This implant had been testedin over 700 patients, before the current, second generation Car-dioSEALTM emerged. The original design was withdrawn fromclinical use because of stress fractures in the supporting arms. Thepresent device consists of two self-expanding, umbrella-like discs

1 Use of the trade names is for product identification only and does notimply endorsement

comfort for the patients. Complete closure rates are high and this approach has become a viable option forASD management.

446 Bennhagen et al.

© Adis International Limited. All rights reserved. Am J Cardiovasc Drugs 2001; 1 (6)

that, after implantation fix, by spring tension, to either side of theatrial septum. Four metal arms made of a metal alloy MP35Nradiate, via hinges, from each of the two disc centers onto eachcorner of the discs. This framework design facilitates con-formability of the implant to the atrial septum with its individualvariations in atrial topography, as well as giving the device a lowprofile along the atrial septum after deployment. Knitted polyes-ter fabric (DacronΤΜ) covers create the disc over the supportingarms. Two coil joints or hinges in each arm, (added in the rede-sign) displace stress during atrial contraction and contribute toimproved fracture resistance.[17] The spring back characteristicsallow the disc/umbrella frames to assume their original shapeafter reexpansion after device delivery. The metal arms of thedevice are more resistant to fatigue fracture than the originalstainless steel formulation in ClamshellΤΜ implant.[17]

The alloy is nonferromagnetic, making magnetic resonanceimaging an investigative option in implant recipients. The Car-dioSEALΤΜ device is front loaded into the distal pod of the de-livery catheter with the aid of a plastic loader and attached to thedelivery catheter through a pin-to-pin attachment mechanism. A10-French sheath is required for the implantation. Car-dioSEALΤΜ is available in five sizes (17, 23, 28, 33, 40mm),corresponding to the diagonal length of each umbrella. Devicediameter is selected to be 1.5- to 2-fold greater than the size ofthe balloon-stretched diameter. In the US, CardioSEALΤΜ hasFDA approval for closure of patent oval foramen, ventricular sep-tal defects and fenestrated Fontan communications. General usein patients with an isolated atrial septal defect awaits finalizationof ongoing clinical trial results. In 1997, the CardioSEALΤΜ wasawarded the Conformite Europeene (CE) marking in Europe, andthe device is approved for general application in Canada.

2.2 The STARFlexΤΜ Device

The STARFlexΤΜ implant is a modification of the Car-dioSEALTM implant. The unique difference consists of a flexible,auto-adjusting, self-centering spring mechanism. Soft, flexible,metallic springs made from nitinol (nickel-titanium alloy) areattached using polyester sutures along the circumferences of thetwo disc frameworks alternating between the two umbrellas.[18]

These microsprings allow the left atrial disc to pivot against theleft atrial septum during deployment as well as facilitating thecentering of the device within the defect. STARFlexΤΜ is cur-rently available in four sizes: 23, 28, 33 and 40mm. It uses a10-French trans-septal delivery sheath. The attachment of the de-vice to the delivery catheter uses a pin-to-pin mechanism, similarto that of the CardioSEALΤΜ. The length of the pin-to-pin attach-ment, however, allows the device to rotate through its attachment,reducing tension between device and interatrial septum. Addi-tionally, the attachment metal wire is made of a smaller diameter

than in the original CardioSEALΤΜ system, allowing greater flex-ibility after the right atrial disc is opened. Both these designchanges allow the device to attain the anatomical atrial positionbefore final release.[17] The loading system and implantation issimilar to that of the CardioSEALΤΜ, although a new rapid load-ing mechanism has recently been released, which reduces han-dling prior to implantation and additionally removes air from thesystem more effectively than previous systems. The STARFlex™loading system is now available for the CardioSEAL™, reducingthe catheter profile. Because of the implants self-centering prop-erties, larger defects, up to 25mm (balloon-stretched) in diameter,can be addressed. As such, defect size (stretched diameter) todevice diameter can be selected such that the ratio diameters arein the 1.5 to 1.6:1 range.[18] High-risk defect clinical trials withthis device, under FDA guidelines, are near completion in NorthAmerica, whilst the CE award was obtained in Europe in 1998.

3. Patient Selection

Indications for transcatheter closure of atrial septal defectsare similar to those for surgical closure. A clinically detectableatrial communication in the septum secundum, resulting in anenlarged right atrium, volume overload of the right ventricle, anda pulmonary to systemic flow ratio of greater than 1.5:1.[6] De-fects unfavorable for catheter closure are the superior sinus ve-nosus defect, unroofed or partially unroofed coronary sinus de-fects, primum atrial defects and the inferior sinus venosus defect.Additionally, those defects whose rims include the orifice of theinferior vena cava are not suitable for closure.

Indications for closure are less clear in early childhood andin elderly patients. If the defect is diagnosed in infancy or earlychildhood, the size of the defect on 2-dimensional transthoracicechocardiogram (TTE) or color-coded Doppler flow mapping(CCD) in end-systole, may predict its natural history.[19] Defects<3mm in diameter will almost certainly close spontaneously. De-fects between ≥3 and ≤5mm in diameter will close in up to 90%of cases, those between >5 and <8mm in 80% of cases and thosedefects ≥8mm in diameter will rarely close spontaneously. In theabsence of symptoms, closure (surgical or catheter-based) is gen-erally postponed until the patients is 4 to 6 years of age. In elderlypatients, surgical defect closure improves symptoms of exerciseintolerance and possibly mortality over the short term.

Criteria for transcatheter are listed in (table I). After initialscreening with TTE, chest radiography and ECG, selected pedi-atric patients are further evaluated by transesophageal echo-cardiography (TEE) under general anesthesia, although TEE canbe performed under sedation alone in adults. TEE reassesses thesize and location of the defect, the surrounding rims, length of theatrial septum and the proximity to the pulmonary veins. A clearerunderstanding of interatrial septal anatomy, with the recent intro-

Management of Children with ASD 447


duction of 3-dimensional transesophageal echocardiographic re-constructions (3D-TEE),[20-24] coupled with improvements incatheter technique have broadened the selection criteria. Patientswith partial deficiency of septal rims, a multiperforated septalwall, septal aneurysms in the oval fossa, combined with an atrialseptal defect or up to two perforations,[25] multiple or irregularlyshaped atrial defects or unusually located oval defects can alsobe managed with transcatheter techniques.[26] Finally, patientswho have had a fenestrated Fontan procedure and patients expe-riencing cerebral vascular accidents with an ascertained patentoval foramen, comprise two recent groups for transcatheter clo-sure of the communication.[26-30]

4. Device Implantation Technique

4.1 Preparation

General anesthesia and TEE guidance are prerequisites foroptimal device positioning and maximum patient safety.[31] Im-portant anatomical landmarks on TEE prior to closure are theanterosuperior rim (distance to the aorta), the anteroinferior rim(distance to the tricuspid valve annulus), the posterosuperior rim(distance to the superior caval vein) and the posteroinferior rim(distance to the inferior caval vein). After percutaneous entry ofthe femoral vein, a complete hemodynamic evaluation is gener-ally performed. A contrast injection in the right upper pulmonaryvein to outline the atrial wall and defect (30° Left AnteriorOblique, 30° Cranially) has largely been replaced by TEE. Afterheparinization, an end hole catheter is passed through the defectinto the left upper pulmonary vein. A hand injection of the con-trast medium is undertaken to outline the catheter, for later use inquantification for magnification correction, although markercatheters and external references have been useful as well. Anexchange length, 260cm, guide wire (Cook, Bloomington, IN,USA) is then introduced into the catheter and the catheter is re-moved.

4.2 Estimating the Size of the Defect

There are several ways to estimate the size of the defect.While 2- and 3-dimensional imaging can define the defect mar-gins, it has been reported that the muscular margins are the effec-tive anchors for the closure. To determine the muscular marginsboth static and dynamic methods have been employed. Over theguide wire, placed into the pulmonary vein, a round occlusionballoon (Meditech, Watertown, MA) can be advanced through thedefect and into the left atrium. The balloon is inflated with amixture of contrast and saline, and under fluoroscopic and TEEguidance, pulled gently towards the atrial septum. This procedureis repeated, with varying degrees of balloon inflation, until an

indentation or deformation is seen on the balloon. A cineangio-gram is obtained of the deformed balloon. The width of the de-formation is measured, and this length is designated as the bal-loon-stretched diameter. After confirmation of complete balloonocclusion of the defect, CCD interrogates the presence of anyadditional atrial septal defect(s). If found, their size(s), location(s)and distance(s) from the central defect are defined. On the otherhand, the static method of defect diameter determination usesballoons (NuMed Inc., Nicholville, NY, and AGA Medical, Gold-en Valley, MN) made from highly compliant material and oblongin shape. These balloons deform easily when inflated across thedefect without the need to pull the balloon against the septum.Inflation is stopped when an indentation is first seen along theballoon length.

The two methods of defect sizing are not comparable. Thefirst method is truly a stretch defect measurement as the marginsare in contact with the balloon, whilst the second is more fillingthe defect. If the defect is irregular, the former method placestension on the lower margins of the defect (septum primum), butmay not stretch the entire lesion circumference. Either sizingtechniques effect upon oblong, noncircular lesions is not fullyunderstood, particularly regarding the choice of device and de-vice size, although 3D-TEE could be insightful.[20-24] Not surpris-ingly, there is a poor correlation (r = 0.41) between the defect sizemeasured by 3D-TEE and the balloon-stretched diameter.[22]

Moreover, the stretched diameter varies with the shape of thedefect (r = 0.35 for complex and r = 0.68 for circular defects[24]).Recently, intracardiac echocardiography (AcuNav™, AcusonCorporation, Mountain View, CA) has allowed visualization ofthe atrial septum in real time during the procedure, possibly mak-ing TEE unnecessary.[32,33] This latter technology may be veryimportant in adults, in whom general anesthesia may not be nec-essary.

In order to avoid implantation of an oversized device, partic-ularly in patients with small build and large defects, the length of

Table I. Criteria for transcatheter closure of secundum atrial septal defects.

Presence of a secundum atrial septal defect.

Documented left to right shunting across the defect.

Recommended maximal defect diameter of 20mm. Relative indication ifdefect ≤24mm

Dilated right ventricle with evidence of volume overload.

A substantial rim, usually 4 to 5mm, between the margins of the defectand nearby intracardiac structures (atrioventricular valves, superior andinferior vena cavae, pulmonary veins and coronary sinus).

Adequate rim of tissue around at least 75% of the defect circumference.

Atrial volume large enough to accommodate the device, usually anindividual >2 years of age or >10kg. Peripheral venous vasculatureshould be able to accommodate a 10- or 11-French sheath.



the atrial septum should measured and compared with the size ofthe selected device. Depending on the texture and thickness ofthe interatrial septum, distension and overestimation of the defectsize may occur.[26] Measurement of a defect considerably smallerthan expected suggests passage of the balloon catheter throughan unappreciated smaller second defect. When multiple defectsare present, a single device can be implanted if it is estimated thatit would cover all of the defects. In this regard, it may be necessaryto pass the sheath through the more central defect and TEE maybe useful in determining catheter location. Two defects distantfrom each other, can also be closed with two devices through twoseparate sheaths.[26] Such devices may overlap slightly after im-plantation.

4.3 Loading the Device

The selected device is soaked in saline to remove air and thenconnected to the delivery or core wire (0.014’’ for Car-dioSEALΤΜ, 0.013’’ for STARFlexΤΜ) by activating the pin-to-pin mechanism. The delivery wire is positioned inside the deliv-ery catheter. By pulling on the arms of the distal umbrella, thesearms will collapse, allowing the proximal umbrella to be pulledthrough a loading cylinder collapsing the proximal arms. There-after the entire device can be loaded into the cylinder. With thedelivery wire, the collapsed device is pulled out of the loadingcylinder and into a plastic pod at the end of the delivery catheter.

4.4 Device Delivery

A long sheath, with dilator is advanced over the guide wireinto the pulmonary vein. To avoid air entry into the system, acontinuous infusion of heparinized saline can be maintainedthrough a side arm attached to the dilator of the long sheath.Flushing starts before the system is introduced through the skin.The sheath and dilator are passed to the level of the hepatic por-tion of the inferior vena cava. While holding the dilator, the sheathis advanced over the guide wire into the left atrium towards theleft upper pulmonary vein. During this maneuver, fluid underpressure, continuously passes through the dilator. No attempt towithdraw blood from the sheath is made once in position. In theadult, a continuous flushing solution may not be necessary andthe sheath may be aspirated once in the pulmonary vein. Aftercrossing the defect with the sheath, the dilator and the guide wireare carefully removed. It is important to keep the end of the dilatorbelow the level of the heart, or using a water-lock, upon with-drawal.

The next step is to advance the loaded device, with attacheddelivery wire, into the long sheath until the distal arms are fullyunfolded into the center of the left atrial cavity. Care is taken toavoid entrapment of the device within the left atrial appendage,pulmonary veins or the mitral valve apparatus. Under TEE guid-

ance, the entire system is pulled back gently toward the left atrialwall, the center of the device positioned just within the left atriumfor the CardioSEALΤΜ implant and just until the left atrial um-brella slightly contacts the left side of the atrial septum with theSTARFlexΤΜ. In most cases, this is in the region of the an-terosuperior portion of the septum. Attempts should be made tobring the device into parallel alignment with the atrial septum, byrotation of the system (sheath and delivery catheter). The devicecan be recaptured i.e. refolded, by retracting the delivery wirewith the attached device into the sheath. Pre-shaping the longsheath and forming a slight curve with a posterior direction at itsend, directs the device more posteriorly in the left atrium and maybe helpful. Positioning the sheath into the right upper pulmonaryvein is an alternative option. Rotation of and/or repositioning thesystem may also be necessary to achieve optimal contact betweendevice and septum to close multiple or unusually located de-fects.[20] When a satisfactory position towards the atrial septumis obtained, the long sheath is further retracted over the deliverywire (which is kept immobile), thereby unfolding the proximalumbrella in the right atrium, affixing itself against the atrial sep-tum. To avoid distortion of the septum, the sheath is fully retractedto the inferior caval vein. While still connected to the deliverywire, the positioning of the device is confirmed by TEE.

4.5 Release of Device, After Release and Retrievability

If the device is in a stable location, not impinging on sur-rounding structures and with acceptable minor residual shunting,the release mechanism is activated by advancement of the deliv-ery wire to disengage the two parts of the pin-to-pin mechanismresulting in device deployment. Usually, this maneuver willslightly alter the device spatial orientation within the atria.

TEE is again employed to confirm the final position of thedevice, evaluate the presence, location and size of residual shunt-ing, rule out systemic or pulmonary venous obstruction, compro-mise of the atrioventricular valve function or indentation of theaortic root. An optional right atrial or inferior caval vein angio-gram with follow through to levophase can be done, for additionalconfirmation. Cephalosporins and heparin sulfate are adminis-tered prior to device implantation. Low aspirin dosage (3 to 5mg/kg daily, maximum: 325mg) is prescribed for 6 months andendocarditis prophylaxis is recommended for the first 6 monthsafter the procedure.

After release, the devices can not be refolded, but can beretrieved with a snare and other snare-like devices.

4.6 Practical Considerations

A common pitfall is to unfold the distal (left atrial) umbrellatoo close to the atrial septum and the defect, which may lead toone of the left disc arms prolapsing through the defect. Another



difficulty that might emerge is when there is an angulation of the3-dimensional topology of the atrial septum, making it difficultto adjust the distal umbrella to be parallel with the atrial defect.Parallel alignment might be accomplished by rotating the distalumbrella towards the right upper pulmonary vein and then gentlyretracting it down alongside the septum.

STARFlexΤΜ is also implanted in a similar way and the de-livery process follows the same steps until the distal arms areunfolded in the left atrium. At this point, in order to activate theself-centering mechanism, the long sheath is pulled back to apoint where the centering microsprings between the umbrellas areuncovered, but with the tips of the proximal arms still within thesheath.[12] The device can still be recaptured, if not in a favorableposition. Although the microsprings are not visible on fluoros-copy, they can be seen by TEE, appearing as a parachute. Sub-sequently, the entire system is pulled back until the distal um-brella slightly touches the left side of atrial septum. Then, theproximal umbrella is unfolded by fully retracting the sheath, overthe delivery wire (which is kept immobile) into the inferior cavalvein. If the position is satisfactory on TEE, the device can bereleased, and the final result evaluated. There is less device mo-tion (repositioning) of the STARFlexΤΜ, compared with othercardiac implants, in relation to the atrial septum after release be-cause of the flexible push wire and the extended pin-to-pin at-tachment mechanism. After release of the device, it is unusual toobserve changes in position immediately after the procedure, al-though slight positional alterations have been noted in followup.[34]

5. Results

5.1 Immediate Results

5.1.1 CardioSEALΤΜ and STARFlexΤΜ DevicesIn the European multicenter experience[35] with both oc-

cluders, between 1996 and 1999, the procedure was attempted in334 patients (mean age 12 years, mean bodyweight 44kg). Anisolated defect was found in 73% of patients, 6% had multipledefects, 5% a defect with a septal aneurysm, 13% a patent ovalforamen and 3% had a fenestrated Fontan circulation. The meandefect size was 11.5mm by TTE, 12mm by TEE and 15mm byballoon-stretched diameter. Mean device to balloon-stretched di-ameter ratio was 2.16 (range 1.4 to 7). Implantation was accom-plished in 325 patients (97.3%) with a mean fluoroscopy time of18 minutes. A residual leak was detected in 41% of patients im-mediately after the procedure and this persisted in 31% of patientsat time of discharge. Device embolization (minutes to a few hoursafter implantation) was observed in 13 patients (4%). The devicesembolized to the pulmonary artery in 12 cases and to the leftventricle in one. Uncomplicated surgical repair was accom-

plished in 10 of these 13 patients, whilst in three cases the deviceswere retrieved and successful reimplantation was performed witha second device. The device to defect ratio for the embolizeddevices was 1.8 (range 1.5 to 2.2). One patient experienced hemi-plegia 4 hours after implantation.

At the Toronto Hospital for Sick Children, 50 patients (me-dian age 9.7 years) underwent attempted percutaneous occlusionwith the CardioSEALΤΜ implant between 1996 and 1998.[36] Themean defect diameter, estimated by TEE, was 11.9 ± 2.9mm(range 7 to 18mm; median 12mm) and by balloon-stretched di-ameter 13.7 ± 3.2mm (range 7.5 to 20mm; median 14mm). Twodefects were found in ten patients (20%) and a multiperforatedatrial septum was found in one patient (2%). Partial deficiency ofseptal rims (<4mm) was present in 19 patients (38%). Prior toclosure the ratio between pulmonary to systolic blood flow(Qp:Qs) was 1.9 ± 0.7 (range: 1 to 4:1). Fluoroscopy time duringthe procedure ranged from 7 to 32 minutes (mean: 15.5 ± 5.4minutes). Device to balloon-stretched diameter ratio was 2.5 ±0.4 (range: 1.9 to 3.6).

All patients had successful implantations, although in fourpatients (8%) a second device was implanted after removal of amalpositioned initial implant. There were no significant immedi-ate complications. All patients, except one, were dischargedwithin 24 hours, where 40% had a complete closure. Mean followup was 9.9 ± 3.2 months (range 6 to 12 months) and at the latestfollow up, residual shunting was identified in 23 patients (46%).The shunt measured <2mm in 13 patients (26%), 2 to 4mm in fourpatients (8%) and >4 mm in six patients (12%). Of the six patientswith residual shunts >4 mm by CCD, four had normal right ven-tricular size and septal wall motions. In an univariate analysis,defects with little or no rim, particularly in the anterosuperiorportion of the septum, were associated with a higher incidence ofresidual leaking because of prolapse of one arm through the de-fect. However, in a multivariate analysis, no risk factor was pre-dictive of residual shunting. The right ventricular end-diastolicdimension, corrected for age, decreased from 137 ± 29 to 105 ±17% and septal motion abnormalities stabilized in all but onepatient. Device fractures were detected in seven patients (14%).Prolapse of one arm of the device through the defect was notedin 16 patients (32%). No complications occurred because of de-vice fracture or arm prolapse. Five patients (10%) experiencedtransient headaches. There were no episodes of device emboliza-tion, endocarditis, stroke or cardiac-related hospital admis-sions.[36]

5.1.2 Amplatzer® Septal OccluderThis self-expandable, double-disc, biocompatible implant

was introduced in 1996 and was the first in the Amplatzer familygroup of occlusion devices (AGA Medical Corp., Golden Valley,MN, USA).[37] This device also includes a wire mesh stent, com-



posed of Nitinol filled with a polyester material to increasethrombogenicity, promoting thrombosis of the plug. The size ofthe device (4 to 36mm) refers to the occluding waist, i.e. the partbetween the discs, corresponding to the size of the atrial commu-nication. The implants require a 6- to 12-French delivery sheath.It has achieved widespread clinical application, with ease of im-plantation and near complete occlusion in defects sized up to36mm in diameter. A successful implantation rate of 90%,[38]

91.1%[39] and 96.1%[40] have been reported, with a trivial, hemo-dynamically insignificant residual shunt remaining. Defects witha balloon-stretched diameter up to 38mm have been implantedwith success.[41] A missing anterior rim at the aortic root is nolonger a contraindication for device closure.[39]

5.1.3 Das-Angel Wings ΤΜ DeviceDas developed this device 1993 (Microvena, Vadnais, MN,

USA).[42] It has a low profile against the atrial septum comparedwith other atrial septal occluders. Composed of DacronΤΜ sewntogether to form abiatrial discs with an occluding center ring. Sizeranges from 18 to 40mm and refers to the length of the squareddisc, equal and 90 degrees off set for the left and the right atrialsides. A multicenter FDA pilot study has shown encouraging re-sults,[43] indicating that the device is both effective and well tol-erated.

5.1.4 ASDOS DeviceΤΜ

This Atrial Septal Defect Occluder System (ASDOS) implant(Osypka Corp., Germany) was first described in 1991.[44] It iscomposed of a Nitinol metal frame work covered with a mem-brane of microporous polyurethane. It is available in sizes from25 to 60 mm. The main difference to other devices is the need ofa snaring technique (a guidewire is snared, and exteriorizedthrough the femoral artery) as a part of device delivery, necessi-tating an arterial access.

5.1.5 Buttoned DeviceTΜ

Clinical trials beginning in 1990[45] the so-called Button De-vice, (Custom Medical Devices, Amarillo, TX, USA), consists ofthree parts. In addition to a standard long sheath delivery system,it is comprised of an occluder disc and a counter-occluder fixatingarm, each is ntended to be expanded on either side of the atrialseptum. It requires an 8 to 9 French sheath and is available in sizesfrom 25mm to 50mm. Initial problems with unbuttoning has re-quired several redesigns, now with the fourth iteration devicefailure rate increasing to 1%. A recent modification has adopteda self-centering mechanism.[46]

5.1.6 HELEX Septal OccluderThe HELEX Septal Occluder (WL Gore & Associates, Inc.,

Flagstaff, AZ) is the latest contribution to the family of perma-nently implanted prostheses for closure of secundum atrial septal

defects. It is composed of expanded PTFE patch material sup-ported by a spiral shaped nitinol wire frame. Its main advantagebeing a safety cord that allows the device to be removed afterdelivery.[47] The use of HELEX Septal Occluder is still restrictedto an investigational device.

5.2 Healing Process

With the device (CardioSEALΤΜ)in situ the usual healingprocess is initiated. In long-term animal studies,[48] neointimawas noted to cover the device to at least 50% of its diameter afterone month and completely by three months after implantation.After 2 years, the encapsulated device becomes densely organizedwith fibrous tissue and neovascularized, simultaneously with apersistent foreign body reaction between the device and sur-rounding tissue.

5.3 Adverse Events

Device fracture, dislocation and embolization are possibleadverse events associated with device implantation. However,these adverse events have become rarer with improved deviceengineering and delivery techniques and greater clinical experi-ence with their use. One isolated case of left atrial wall erosionhas been described.[36] Thromboembolic events can occur, de-spite antiplatelet therapy during and after the intervention, partlydepending on the patients pre-interventional condition. Alterationin atrioventricular valve function can be avoided with TEE. Witha meticulous implantation technique, air embolism can be elimi-nated. Finally, postprocedural headaches have been describeddays after the implantation, and the etiology of this phenomenonis not yet fully understood. These headaches are adequatelytreated with acetaminophen (paracetamol).

6. Follow-Up

Various follow-up protocols have been applied. After dis-charge (usually within 24 hours of the procedure), clinical eval-uation, chest radiography, ECG, Holter monitoring andechocardiography have been recommended at regular intervalswhen clinically indicated. Regular TEE is also advocated by someauthors.[26] Right ventricular end-diastolic dimensions have beenmeasured serially after the procedure and tend to reach expectedvalues, compared with predicted values for age, over time.[31] Inthe European Multicenter CardioSEALΤΜ study,[35] residualshunting persisted 24% of patients at 1 month, 21% of patients at6 months and in 20.5% of patients at 12 months after implanta-tion. Two patients underwent elective surgical repair at 6 months.The indication in one patient was device malposition and in an-other late device embolization. Device arm fractures were seenin 19 of 309 patients (6.1%), and all patients remained asymp-



tomatic. Such fractures occur most commonly with larger devices(23mm, n = 1; 28mm, n = 1; 33mm, n = 7; 40mm, n = 10).[35] Inthe pediatric population, there have been no long term symptom-atic arrhythmias, endocarditis, valvular distortion, or thrombo-embolic events. At 1 year follow-up, clinical success, defined ascomplete closure of the defect or presence of a trivial leak, wasobserved in 99 of 107 pediatric patients (92.5%). A study withlonger median follow-up[17] (31 months, range 7 to 56 months)with a double umbrella device (USCI Angiographics, Glensfalls,NY) found a higher occurrence of device arm fractures and inci-dence of residual, hemodynamically nonsignificant, shunting af-ter 4 years (in 42 and 36% of patients, respectively). However,progressive spontaneous shunt resolution continued years afterimplantation.

Drug therapy does have a place in the symptomatic treatmentof patients with atrial septal defects. Diuretics given as palliationdirected to decrease pulmonary overcirculation can improve ex-ercise performance. However, in the symptomatic patient, closureis the treatment of choice. Atrial defects associated with second-ary pulmonary hypertension, an effect of large flow, should beclosed if the pulmonary resistance is either low, or found on in-vestigation to be reactive to drugs (e.g. nitric oxide, oxygen)which reduce resistance.

7. Discussion and Conclusion

Implantation of the CardioSEALΤΜ or other implants cor-rects the hemodynamic disturbances in ventricular septal motion,right atrial and ventricular dimensions which occur secondary tothe right ventricular volume overload and pulmonary hyperperfu-sion. Small residual leaks that can be detected in a few at followup appear to be of little clinical importance. Although little datais available, results suggest that the rate of residual leaks is lowerwith the STARFlexΤΜ design.[35] The low profile of the Car-dioSEALΤΜ and STARFlexΤΜ designs facilitate endothelializa-tion and minimize the risk of thrombus formation in the atria.Device fractures have not been completely eliminated with Car-dioSEALΤΜ, although the incidence is clearly lower comparedwith the ClamshellΤΜ implant.[26,35] The presence of fractures isnot associated with an increased rate of residual shunting, deviceembolization or any clinical complication. The relatively highincidence of headaches detected after device closure is an inter-esting observation of unknown etiology. The release of vaso-active mediators from platelets during the early process of en-dothelialization, or vasoactive hormones, or to increased leftatrial or decreased right atrial pressures and volumes, after defectclosure, are several possible explanations in the genesis of thesesymptoms. In comparison, the more flexible microspring center-ing mechanism in the STARFlexΤΜ design does not distort theatrial septum during implantation to the same extent as with Car-

dioSEALΤΜ . [18] The spring coil design allows for positioning ofeach arm, and reduces the stress forces between the device andthe atrial septum. Because of the STARFlexΤΜ self-centeringmechanism, relatively smaller devices can be used to close sim-ilar sized defects and correspondingly, larger defects, up to 25mmballoon-stretched diameter, can be also closed with this implant.The issue of the surrounding rim appears to be less critical forimplantation with the later design.[18]

CardioSEALΤΜ, with or without the STARFlexΤΜ design, isa self-expanding, double umbrella cardiac implant designed topermanently close small to moderate secundum atrial defects.Defects that are unusually located, multiple, or with just a partialrim can be addressed with these devices with a good result. Over-all, successful defect occlusions occur in >92% of patients al-though small residual leaks are commonly seen with Car-dioSEALΤΜ. These leaks tend to resolve or decrease over time,with little if any hemodynamic importance to the right ventricle.STARFlexΤΜ offers several advantages because of its self-center-ing mechanism, which will improve results such as closure rate,lack of device arm fractures, prolapse, device dislocation and riskof cardiac perforation. A better understanding of the anatomy andmorphology of atrial septal defects and other atrial communica-tions, modifications in implantation techniques and device designrefinements have extended the limits of transcatheter closure ofatrial communications in therapeutic cardiac catheterizations.Ostium primum, sinus venosus and atrial septal defects are con-sidered not suitable for closure. Relative indications are multipleatrial septal defects, lack of substantial rim around the defect,short septal length and a small left atrium. The methods to esti-mate the defect diameter are currently under debate.

Acknowledgements

Dr. Rolf Bennhagen was supported by The Foundation Marcus and AmaliaWallenberg Memorial

References1. Feldt RH, Avasthey P, Yosimasu F, et al. Incidence of congenital heart disease in

children born to residents of Olmstead County, Minnesota, 1950-1969. MayoClin Proc 1971; 46: 794-9

2. Keith JD. Atrial septal defect: ostium secundum, ostium primum andatrioventricularis communis (common AV canal). In: Keith JD, Rowe RD, VladP, editors. Heart disease in infancy and childhood. 3rd ed. New York: Macmill-ian, 1978:380-404

3. Nakamura FF, Hauck AJ, Nadas AS. Atrial septal defects in infants. Pediatrics,1964; 34: 101-6

4. Porter Co-burn J, Feldt RH, Edwards WD, et al. Atrial septal defects. In:Emmanouilides GC, Allen HD, Riemenschneider TA, et al., HP editors. Mossand Adams Heart Disease in Infants, Children, and Adolescents including theFetus and Young Adults. 5th ed. Vol 1. Baltimore, Maryland: Williams & Wil-kins, 1995:687-703

5. Gatzoulis MA, Elliot JT, Guru V, et al. Right and left ventricular systolic functionlate after repair of tetralogy of Fallot. Am J Cardiol 2000 Dec 15; 86 (12):1352-7



6. Latson LA. Per-catheter ASD closure. Pediatr Cardiol 1998; 19 (1): 86-93

7. Kirklin JW, Barrat-Boyes BG. Atrial septal defect and partial anomalous pulmonaryvenous connection. In: Kirklin JW, Barratt-Boyes BG, editors. Cardiac Surgery.2nd ed. New York: Churchill Livingstone Inc., 1993: 624-632

8. Galal M, Wobst A, Halees Z, et al. Peri-operative complications following surgicalclosure of atrial septal defect type II in 232 patients - a baseline study. Eur HeartJ 1994; 15: 1381-4

9. Izzat MB, Yim AP, El-Zufari MH. Limited access atrial septal defect closure andthe evolution of minimally invasive surgery. Am Thorac Cardiovasc Surg 1998;4 (2): 56-8

10. Matsuzaki K, Koniski T, Fukata M, et al. Minimal incision cardiac surgery for atrialseptal defects. J Cardiol 2000; Apr;35 (4): 297-300

11. Formigari R, Di Donato RM, Mazzera E, et al. Minimally invasive or interventionalrepair of atrial septal defects in children: Experience in 171 cases and compar-ison with conventional strategies. J Am Coll Cardiol 2001 37 (6):1707-1712

12. King TD, Thompson SL, Steiner C, et al. Secundum atrial septal defect: nonopera-tive closure during cardiac catheterization. JAMA 1976; 235: 2506-9

13. Lock JE, Rome JJ, Davis R, et al. Transcatheter closure of atrial septal defects:experimental studies. Circulation 1989; 79: 1091-9

14. Rome JJ, Keane JF, Perry SB, et al. Double-umbrella closure of atrial septal defects:initial clinical applications. Circulation 1990; 82: 751-8

15. Bjornstad PG. The role of devices in the closure of atrial septal defects in the ovalfossa. Cardiol Young 1998; 8: 285-6

16. Wilkinson JL. Can transcatheter closure of atrial septal defects be regarded as a‘standard procedure ?. Cardiol Young 1999 Sep 9 (5):458-461

17. Latson LA. The CardioSEAL device: history, techniques, results. J Interv Cardiol1998; 11: 501-5

18. Hausdorf G, Kaulitz R, Paul T, et al. Transcatheter closure of atrial septal defectwith a new, flexible, self-centering device (The Starflex Occluder). Am Heart J1999; 84: 1113-6

19. Radzik D, Davignon A, Van Doesburg N, et al. Predictive factors for spontaneousclosure of atrial septal defects diagnosed in the first 3 months of life. J Am CollCardiol 1993; 22: 851-3

20. Acar P, Piechaud JF, Bonhoeffer P, et al. Anatomic evaluation of ostium secundumatrial defects by three-dimensional echocardiography. Arch Mal Coeur Vaiss1998; 91: 543-50

21. Acar P, Saliba Z, Bonhoeffer P, et al. Influence of atrial septal defect anatomy inpatient selection and assessment of closure with the Cardioseal device; a three-dimensional transoesophageal echocardio graphic reconstruction. Eur Heart J2000; 21: 573-81

22. Acar P, Bonhoeffer P, Saliba Z, et al. Three-dimensional reconstruction by trans-esophageal echocardiography of Amplatzer and CardioSEAL prosthetic devicesafter percutaneous closure and atrial septal defects. Arch Mal Coeur Vaiss 2000;93: 539-45

23. Maeno YV, Benson LN, Boutin C. Impact of dynamic 3D transesophagealechocardiography in the assessment of atrial septal defects and occlusion by thedouble-umbrella device (CardioSEAL). Cardiol Young 1998; 8: 368-78

24. Acar P. Three-dimensional echocardiography in transcatheter closure of atrial sep-tal defects. Cardiol Young 2000; 10: 484-92

25. Ewert P, Berger F, Vogel M, et al. Morphology of perforated atrial septal aneurysmsuitable for closure by transcatheter device placement. Heart 2000; 84: 327-31

26. Kaulitz R, Paul T, Hausdorf G. Extending the limits of transcatheter closure of atrialseptal defects with the double umbrella device (CardioSEAL). Heart 1998; 80:54-9

27. Chambers J. Should percutaneous devices be used to close a patent foramen ovaleafter cerebral infarction or TIA ? Heart 1999; 82: 537-8

28. Van Camp G, Schulze D, Cosyns B, et al. Relation between patent foramen ovaleand unexplained stroke. Am J Cardiol 1993; 71: 596-8

29. Bridges ND, Hellenbrand W, Latson L, et al. Transcatheter closure of presumedparadoxical embolism. Circulation 1992; 86: 1902-8

30. Hung J, Landzberg MJ, Jenkins KJ, et al. Closure of patent foramen ovale for

paradoxical emboli: intermediate-term risk of recurrent neurological events fol-

lowing transcatheter device placement. J Am Coll Cardiol 2000; 35: 1311-631. Hellenbrand WE, Fahey JT, McGowan FX, et al. Transoesophageal

echocardiographic guidance of transcatheter closure of atrial septal defect. Am

J Cardiol 1990; 66: 207-13

32. Moscucci M, Daiywala IT, Chetcuti S, et al. Balloon strail septostomy in end-stage

pulmonary hypertension guided by a novel intracardiac echocardiographic

transducer. Catheter Cardiovasc Interv 2001; 52 (4): 530-433. Hijazi Z, Wang Z, Cao Q, et al. Transcatheter closure of atrial septal defects and

patent foramen ovale under intracardiac echocardiographic guidance: feasibility

and comparison with transesophageal echocardiography. Catheter Cardiovasc

Interv 2001 Feb; 52 (2): 194-9

34. Boutin C, Musewe NN, Smallhorn JF, et al. Echocardiographic follow-up of atrial

septal defect after catheter closure by double umbrella device. Circulation 1993;

88: 621-7

35. Carminati M, Giusti S, Hausdorf G, et al. A European multicentre experience using

the CardioSEAL® and Starflex double umbrella devices to close interatrial

communications holes within the oval fossa. Cardiol Young 2000; 10: 519-2636. Pedra CAC, Pihkala J, Lee K-J, et al. Transcatheter closure of the atrial septal

defects using the CardioSeal implant. Heart 2000; 84: 320-6

37. Sharafuddin M, Gu X, Titus J, et al. Transvenous closure of secundum atrial septal

defecs: preliminary results with a new self-expanding nitinol prosthesis in a

swine model. Circulation 1997; 95: 2162-8

38. Walsh KP, Maadi IM. The Amplatzer septal occluder. Cardiol Young 2000; 10:493-501

39. Berger F, Ewert P, Abdul-Khaliq H, et al. Percutaneous closure of large atrial septaldefects with the Amplatzer Septal Occluder: Technical overkill or recommend-

able alternative treatment ? J Interv Cardiol 2001; 14 (1): 63-7

40. Waight DJ, Koenig PR, Cao Q-L, et al. Transcatheter closure of secundum atrial

septal defects using the Amplatzer Septal Occluder: Clinical experience and

technical considerations. Current Interventional Cardiology Reports 2000; 2:70

41. Berger F, Ewert P, Bjornstad PG, et al. Transcatheter closure as standard treatment

for most interatrial defects: Experience in 200 patients treated with the

Amplatzer Septal Occluder. Cardiol Young 1999; 9: 468-7342. Das GS, Voss G, Jarvis G, et al. Experimental atrial septal defect closure with a

new, transcatheter, self-centering device. Circulation 1993; 88: 1754-64

43. Das GS, Hijazi ZM, O’Laughlin P, et al. Initial results of the US, PFO/ASD Closure

trial [abstract]. J Am Coll Cardiol; 1996; 27 Suppl. A: A119

44. Babic U, Grujicic S, Popovic Z, et al. Double-umbrella device for transvenous

closure of patent ductus arteriosus and atrial septal defects: first experience. J

Interv Cardiol 1991; 4: 283-94

45. Sideris EB, Sideris S, Fowlkes J, et al. Transvenous atrial septal occlusion in piglets

using a ‘buttoned’ double disc device. Circulation 1990; 81: 312-8

46. Sideris EB, Leung ML, Yoon JH, et al. Occlusion of large atrial septal defects with

a centering buttoned device: Early clinical experience. Am Heart J 1996; 131:

356-9

47. Latson LA, Zahn EM, Wilson N. Helex Septal Occluder for closure of atrial septal

defects. Curr Interv Cardiol Rep 2000 Aug; 2 (3): 268-7348. Kuhn MA, Latson LA, Cheatham JP, et al. Biological response to Bard Clamshell

Septal Occluders in the canine heart. Circulation 1996; 93: 1459-63

Correspondence and offprints: Dr Lee Benson, The Divisions of Cardiology,The Hospital for Sick Children, 555 University Ave, Toronto, ONT, CanadaM5G1XB.E-mail: [email protected]



contemporary management of children with atrial septal defects

Documents