a biodegradable device (biostar™) for atrial septal defect closure in children

A Biodegradable Device (BioSTARTM) for Atrial SeptalDefect Closure in Children

Gareth Morgan, MB, BaO, BCh, MRCPCH, Kyong-Jin Lee, MD, FRCPC, Rajiv Chaturvedi, MD, PhD,FRCPC, and Lee Benson,* MD, FRCPC, FACC, FSCAI

Background: Percutaneous closure of atrial defects (ASD) has evolved as the treatmentof choice for the majority of defects and patent oval foramens. The BioSTARTM biode-gradable implant avoids many issues associated with devices containing substantialamounts of metal. Methods: Reviewed was a consecutive series of 10 ASD occlusionsin a pediatric population with the BioSTAR biodegradable device. All implantationswere performed by one operator. The inclusion criterion was a balloon stretched ASDdiameter of �16 mm. Procedural data and acute and early-term closure rates were ret-rospectively matched to a cohort of children having defect closure using the AmplatzerSeptal OccluderTM (ASOTM). Results: Acute and 6 month follow up closure rates for theBioSTAR were 90% and 100% vs. 100% and 100% closure with the ASO implants.There was a statistically significant difference in the median procedure time (52 min:BioSTAR; 39.5 min: ASO device, P < 0.05), with fluoroscopy times slightly longer for theBioSTAR group (6.7 min vs. 6.1 min, P 5 ns). There were no significant complicationsin either group. Conclusions: The BioSTAR implant can achieve comparable closurerates to the ASO in small- to moderate-atrial septal defects with only a minimal skele-ton of foreign material remaining after 6 months. Longer fluoroscopy and proceduretimes were a drawback; however, these should improve with familiarity with theimplant and deployment system. VC 2010 Wiley-Liss, Inc.

Key words: atrial septal defect; pediatric interventional cardiology; device occlusion

INTRODUCTION

Closure of most atrial level shunts can be achievedby percutaneous techniques [1]. The most frequentlyused implant is the Amplatzer Septal OccluderTM

(ASOTM AGA Medical Corporation, Plymouth, MN)that posses many key characteristics for consistentocclusion of various defect dimensions and morpholo-gies [1–3]. The ASO device, as with many other devi-ces available, implant forms a relatively large, perma-nent structure on and eventually within the atrial septalwall. As such, concerns regarding potential or realizedmedium to long-term complications have appeared. Inthis regard, there have been examples of late erosion,thought to be due to chronic friction of the implants asthey move against cardiac chamber walls [4–6]. Whilethe acute arrhythmia burden appears lessened by deviceclosure [7,8] the left atrium becomes inaccessible fortransseptal access for assessment and treatment ofacquired or congenital heart rhythm disorders [9],lesions that may not present for many decades after thedefect closure. In addition, such devices cause signifi-cant artifact during magnetic resonance imaging (MR)of the thorax, although the device itself can be usefully

interrogated by the MR [10,11]. Finally, the potentialfor a long-term local and systemic chronic foreignbody reaction exists as is the possibility of such devi-ces interfering with septal dynamics that may createfunctional problems in later years [12–16]. Many (butnot all) of these concerns can be addressed if theimplant could dissolve or be resorbed after an appro-priate period of endothelialization and tissue over-growth. In this article, we investigated the application

Division of Cardiology, The Labatt Family Heart Center, TheHospital for Sick Children, The University of Toronto School ofMedicine, Toronto, Canada

Conflict of interest: Nothing to report.

*Correspondence to: Lee Benson, MD, FRCPC, FACC, FSCAI, The

Hospital for Sick Children, 555 University Ave, Toronto, Ontario,

Canada M5G1X8. E-mail: [email protected]

Received 18 January 2010; Revision accepted 13 February 2010

DOI 10.1002/ccd.22517

Published online 25 May 2010 in Wiley InterScience (www.

interscience.wiley.com)

VC 2010 Wiley-Liss, Inc.

Catheterization and Cardiovascular Interventions 76:241–245 (2010)

of a partially resorbable implant in selected childrenundergoing atrial defect closure.

METHODS

Patient Population

Between the November 1, 2007 and the November30, 2008 all children undergoing atrial defect closureby the primary investigator (LB), with defects balloonsized to �16 mm in diameter had attempted implanta-tion of a BioSTAR implant (see below). Institutionalindications for septal defect occlusion were applied inall cases, being echocardiographic evidence of rightventricular volume overload in the setting of an iso-lated atrial defect. Parental consent was obtained priorto the study in all cases where it was anticipated fromnoninvasive studies, that the defect was small. Duringthis period, 54 children underwent ASD closure withthe ASO implant. The BioSTAR group was matched tochildren undergoing ASD closure with an ASO implant(see Statistics section).

The Device

The BioSTAR implant design was based on theSTARflexTM (NMT Medical, Boston MA) frameworkwith double umbrella stainless steel (MP35N) arms.The framework (arms) is flexible with three interposedspring hinges along each of the eight arms which con-stitute the two discs of the device. A NitinolTM wire isattached to the ends of the eight arms. Two discs ofacellular porcine collagen (Fortaflex

VR, Organogene-

sisTM, CA) are attached over the wire frame and com-pletely resorbed within 6 months of implantation leav-

ing only the metal supporting arms (Fig. 1). The colla-gen product is produced by purification of porcine gutType I collagen, which is laminated and cross linkedto reinforce the membrane. Heparin sulfate is coatedon the patch to reduce the risk of acute thrombus for-mation, but allows endothelialization of the device bydissipating early after implantation. The implant isavailable in 23, 28, and 33 mm diameters.

The Procedure

Sizing and deployment techniques for implantationwere identical to those described for the STARflexusing an 11 Fr. long sheath [17,18], monitored by fluo-roscopy and intracardiac echocardiography (ICE). Thedevice was soaked in a normal saline solution (5 min)to hydrate the collagen discs, which had been dehy-drated for packaging and transport. The device wasthen attached to a bioptome style delivery system thatuses a flexible ball and socket attachment joint, similarto the STARflex, which allows rotation and variationsin the angulation of the device during deployment (Fig.1). The device was subsequently collapsed and loadedinto the delivery system using a loading tube andsutures, which are preattached to the device (Fig. 2).The device diameter implanted was based upon theballoon stretched diameter (development of a waist orstop-flow technique [19,20]) measured from cinefluo-roscopy and ICE, to be between 1.8 and 2 times theballoon diameter (Fig. 3). As such, the largest stretcheddiameter that closure was attempted was 16 mm. In anattempt to avoid anterosuperior arm prolapse, as seenin similarly constructed devices [21], a 5-mm anterosu-perior rim was also required. Follow-up was by

Fig. 1. The BioSTAR implant with the stainless steel arms and Nitinol ring visible throughthe translucent collagen discs (left panel). The photo on the right details the bioptome stylepivoting ball and socket attachment mechanism.

242 Morgan et al.

Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).

transthoracic echocardiography within 24 hrs of theprocedure, a clinic visit with an echocardiogram at 30–60 days and a further clinic visit with an echocardio-gram at approximately 6 months after the procedure.Antiplatelet therapy (acetylsalicylic acid, 3–5 mg/kg/day) was administered and endocarditis coverageencouraged for time of risk for 6 months.

Statistics

Children who had an Amplatzer ASO deviceimplanted were matched to the subjects, according toballoon stretched size, imaging modality, and weight.Demographic, procedural, and follow-up data includinginterval echocardiography were collected in all chil-dren. Paired t-tests were used to compare procedureand fluoroscopy times. Data were presented as medianand ranges (Table I). The study was approved by theInstitutional Research Ethics Board.

RESULTS

Demographic and procedural data are presented inTable I. One operator performed all BioSTAR implantswith 9 of 10 implanted, using ICE guidance, whileonly 2 of 10 ASO implants performed with ICE guid-ance (operator preference). Transesophageal guidancewas used in all other cases. All children had successfuldevice implantations. The median weights and balloonsize diameters were not significantly different betweengroups (Table I). Immediate (within 24 hr) and follow-up (6 months) occlusion rates for both groups were90% and 100% for the BioSTAR and 100% on bothoccasions for the ASO implants. The child who did notachieve immediate complete occlusion had a trivialleak related to prolapse of the superiorly oriented armof the left-sided disc in to the right atrium, similar tothat reported in some STARflex implants [21]. Thisleak decreased at 6 weeks and was <2 mm at 6months. The median difference in procedural times(12.5 min) was statistically significant (BioSTAR: 52min; ASO: 39.5 min, P < 0.05); however, the mediandifference in fluoroscopy time was not (BioSTAR: 6.7min; ASO: 6.1 min, P ¼ NS).

Six 28 mm and four 33 mm devices were implantedin the BioSTAR group, with the ASO device sizesranging from 5 to 20 mm. In one BioSTAR implant, astable position (arm prolapse through the anterosupe-rior (aortic) rim) was not achieved (28 mm device) de-spite a balloon stretch diameter of 10 mm. The implantwas retrieved prior to release and a 33-mm BioSTARdevice successfully implanted in a stable position. Rec-ognition of instability and retrieval of the device wasuncomplicated. The prolapse of the left atrial armsmay have been due to a more oval defect than circular,such that the 28 mm device was not well centered.There were no vascular complications in either group.The recovery time and hospital stay were similar in

Fig. 2. The device folded into the delivery system with theaid of the blue detachable sutures.

Fig. 3. Intracardiac echocardiography showing a centrally positioned ASD (left panel) priorto and after closure with a 33 mm BioSTAR implant (right panel).

Biodegradable Device Atrial Defect Closure 243


each group, all discharges being the day of the proce-dure or the following day (n ¼ 1, as a significant traveldistance was involved for the family). There were noacute or follow-up thrombotic or bleeding complica-tions in either group.

DISCUSSION

This study is, to our knowledge the first to comparethe BioSTAR device for closure of ASD’s with theAmplatzer ASO in a matched cohort study. The Bio-STAR implant has been available in Europe for patentoval foramen and atrial septal defect closure since 2006,and used in North America primarily for patent oval fo-ramen closure for recurrent stroke prevention [22–24].There is a limited pediatric experience and few studiesassessing efficacy in secundum atrial septal defect clo-sure [25]. The patient population in the BEST study[22] was exclusively adults and only 4 of the 58 patientsincluded had an ASD with right heart dilation. In oneASD case, the device partially prolapsed through thedefect and was replaced with a different type of device.

The BioSTAR device represents an important step inthe development of septal occluders. It uses a testedplatform incorporating unique biomechanics to producea resorbable device. The potential benefits of as suchdevices are decreased long-term thrombogenicity, pre-served transseptal access, decreased inflammatoryresponse, and reduced arrhythmogenicity and erosionpotential. The lifespan and chronic mechanical stressupon the device are of less importance since theimplant is replaced by fibrous endothelialized tissue.One potential concern is resorption of the collagen ma-trix, prior to the overgrowth of endocardial tissue overthe device, leading to a recurrent defect and shuntacross the device. In contrast to the patent oval foramen

closure population in an ASD there is a true tissue defi-ciency, and therefore a true hole in the septum. In thisregard, at 6 months there was no evidence of a residualcentral shunt in any child, suggesting that the tissueresponse to the BioSTAR is sufficient to induce growthof tissue over its entire surface. Only 1 child had a triv-ial residual shunt (<2 mm) in an area of a prolapsedanterior arm of no hemodynamic significance. Finally,while this device has many of the attributes of a fullyabsorbable implant, it will produce an MRI artifact[26]. The next generation in device development, afully absorbable implant (BioTREKTM, NMT Medical)is currently undergoing preclinical trials.

The ASO device continues to be the most widelyused septal occluder because of its simple deploymenttechnique, applicable defect size range, and occlusionrate, but without characteristics that make the BioSTARattractive. The HelexTM septal occluder (W. L. Goreand Associates, Flagstaff, Ariz, USA), is also a soft,low-profile implant with a low metallic composition. Ithas been widely used for patent oval foramen and ASDclosure. The device is not bioresorbable and suffersfrom a relatively complex and cumbersome deliverysystem and implantation technique [27]. The BioSTARdeployment technique is similar to the STARfleximplant for the secundum atrial septal defect and wellcharacterized. However, the 11 Fr. sheath is larger thanthe sheath required to deploy a similar sized ASO de-vice (7 or 8 Fr.) but has obvious advantages comparedto the need for a larger sheath size. Indeed, trauma tothe femoral vein has not been an issue in the use oflarge sheath in this age and weight range. The packag-ing and preparation of the device is comparatively sim-ple, preloaded in to the delivery cable.

The applicability of the BioSTAR will remain lim-ited because of the relative infrequency of small to

TABLE I. Demographics and Outcomes

BioSTARTM Amplatzer ASOTM

Median age (years) (range) 11.0 (4.2–16.3) 7.4 (4.0–12.5)

Median weight (kg) (range) 39.6 (16.5–169.0) 23.3 (16.3–33.1)

Median defect size (mm) (range) 10 (8–15) 10.5 (7–16)

Median balloon stretched

size (mm) (range)

11.5 (9.0–16.0) 12.7 (11.0–16.6)

Device size (mm) 28 n ¼ 1 10 n ¼ 1

11 n ¼ 2

12 n ¼ 1

33 n ¼ 9 14 n ¼ 3

15 n ¼ 1

18 n ¼ 2

Median procedure time (min) (range) 52 (34–100) 39.5 (35–49)

Median fluoroscopy time (min) (range) 6.7 (4–15) 6.1 (4–12)

Closure: 1 day 90% 100%

Closure: 30 days 90% 100%

Closure: 6 months 90% 100%

244 Morgan et al.


moderate atrial defects requiring closure [28]. Indeed,during this series, 54 children underwent ASO deviceimplantation (defects > 16 mm stretched diameter)identifying only 10 appropriate BioSTAR implants.Given the device’s unique biomechanical features, theprocedural and early term follow up and the potentialintrinsic benefits, the BioSTAR implant should be con-sidered in cases of a small to moderate defect with theappropriate morphology.

This study demonstrates that BioSTAR device im-plantation is feasible and safe in the closure of secun-dum type atrial defects up to 16 mm (stretched) in di-ameter, with excellent early term outcomes. Given thefamiliarity of most operators with the STARflex plat-form, the technical application in the clinical setting,i.e., the learning curve may be steep.

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Biodegradable Device Atrial Defect Closure 245


a biodegradable device (biostar™) for atrial septal defect closure in children

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