Transcatheter Ventricular Septal Defect Closure With a New Nanoplatinum-Coated Nitinol Device in a Swine Model

Abstract: Objectives. To evaluate the feasibility and efficacy of a new nanoplatinum-coated nitinol device for transcatheter ventricular septal defect (VSD) closure in a swine model. Background. In spite of its good closure results, the previous version of Amplatzer perimembranous VSD device had a relatively high incidence of complete heart block as compared to surgical closure. This new VSD device is made from meshed nitinol wires, nanoplatinum-coated and filled with polypropylene sheaths to enhance thrombogenicity. With special design, the device has minimal expanding pressure on the nearby tissue. This may reduce the possibility of atrioventricular block after implantation. Methods. VSD was created in 12 pigs via retrograde aortic approach, by ventricular septal puncture with Brokenbrough needle and ventricular septal balloon dilation, under echocardiographic and fluoroscopic guidance. After imaging study, the device was deployed for VSD closure. Results. The device was successfully deployed to close the created VSD in all 12 animals. Angiographic and echocardiographic studies demonstrated complete closure of the VSD in 11 animals. One animal had residual VSD leakage. Three animals had unstable hemodynamics and died within 12 hours after the procedure. The remaining 9 animals survived in normal condition. The autopsy findings demonstrated complete endothelialization at 8 weeks after implantation. Conclusion. Transcatheter VSD closure with the new nanoplatinum-coated nitinol device is feasible and efficacious. The good occlusion results and complete endothelialization after implantation in the swine model potentiates human application.

J INVASIVE CARDIOL 2013;25(10):525-528

Key words: nanoplatinum-coated nitinol device, transcatheter ventricular septal defect closure, VSD closure

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Transcatheter device closures of congenital heart defects such as atrial septal defect and patent ductus arteriosus have been reported with excellent outcomes. However, device closure of ventricular septal defect (VSD) is still a challenging issue. The previous version of Amplatzer device for perimembranous VSD closure had good closure results, but also had complete atrioventricular block requiring pacemaker implantation at a rate of 1.0%-5.7%,^1-5 which is higher than the incidence of 0.8% by surgical closure.^6,7 The explanation of complete heart block by device closure may be due to the expanding force from the central waist of the device on the atrioventricular conduction pathway in the surrounding tissue. With this hypothesis, we designed a new, double-disc, nanoplatinum-coated nitinol VSD device that has minimal expanding pressure from its central waist on the nearby tissue. The purpose of this study was to evaluate its feasibility and efficacy for VSD closure in an animal model prior to human application.

Methods

Device design. The device is constructed from meshed nanoplatinum-coated nitinol wires that are shaped into two symmetrical circular discs connected together by a central waist and filled with polypropylene sheaths to enhance thrombogenicity (Figure 1). The design concept of the device focuses on the strong discs and the soft central waist. Both of the symmetrical discs are designed to be able to tolerate the high pressure of the left ventricle. When compressed, the soft central waist elongates instead of creating the resistance against the compressing force. The disc in the left ventricle (after deployment) plays the major role in occlusion effect and device stability. The sizes of the device are quoted as the diameter of the central waist and the length of the central waist. The central waist diameters are in even numbers from 6 to 12 mm. Its lengths are designed as 4, 7, and 10 mm. Due to the symmetry of the discs, the device can be loaded either from the left or the right heart.

Animal model and procedure. All animals were treated according to the “Guide for the Care and Use of Laboratory Animals” (Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, 1996). The study protocol was approved by the Animal Care and Use Committee, Faculty of Veterinary Science, Mahidol University. Under general anesthesia, venous approach (via femoral vein or internal jugular vein) and arterial approach (via common carotid artery) were performed by cutdown and insertion of 10 Fr vascular sheaths. A dilator of the 8 Fr Mullins long sheath was introduced along a Teflon-coated guidewire via carotid arterial sheath, and retrograded to the ascending aorta and through the aortic valve into the left ventricle. Left ventriculogram was performed to line the ventricular septum. As the tip of the Mullins sheath dilator was pointed toward the ventricular septum at the level just below the aortic valve, a Brokenbrough transseptal needle (BRK-1; St Jude Medical) was inserted along the lumen of the dilator to puncture the ventricular septum and advanced into the right ventricle. Then, the dilator was introduced along the Brokenbrough needle through the ventricular septum into the right ventricle. The Brokenbrough needle was exchanged by a Teflon-coated guidewire. The guidewire was further advanced into the pulmonary artery. An arteriovenous loop was performed by snaring the guidewire to the internal jugular or femoral vein. A balloon dilation catheter, 10 or 12 mm in diameter (Smash; Boston Scientific Corporation) was introduced and advanced along the guidewire to place at the ventricular septum in order to dilate the septum. After balloon dilations, a left ventriculogram was performed to demonstrate and measure the size of the created VSD. The size of the VSD device was selected as the same number or 1-4 mm larger than that of the created VSD. An 8 Fr long vascular sheath was introduced over the looped guidewire, via the arterial or venous route, and advanced through the created VSD. The device was loaded into the sheath and deployed to close the VSD. Repeated angiogram was performed to evaluate the closure result. Figures 2 and 3 summarized the fluoroscopic and echocardiographic imaging of the procedure. 

The animals were observed in the recovery area with postoperative monitoring until stable and were then transferred to the feeding area. The autopsy was performed at the various days after the procedure to study the device alignment, closure result, and tissue reaction to the device.

Results

There were 12 animals included in the study. A VSD was successfully created in all 12 animals. The diameter of the balloon used to dilate the ventricular septum ranged from 10 to 12 mm, with a mean of 10.5 ± 0.9 mm. The size of the created VSD by angiography ranged from 5.8 to 8.1 mm, with a mean of 6.8 ± 0.9 mm. The VSD device was successfully deployed in all 12 cases. The device was loaded from the left heart (via carotid artery) in the first 7 cases and from the right heart (via femoral or jugular vein) in the last 5 cases. The device size (central waist diameter) ranged from 6 to 10 mm, with a mean of 8.3 ± 1.7 mm. The length of the central waist varied from 4, 7, and 10 mm. Table 1 summarizes the detailed information. Three animals had unstable hemodynamics during the procedure and died within 12 hours of the procedure. The remaining 9 animals survived and were normally fed. One animal had residual VSD leakage detected by echocardiographic study. The autopsy in this animal at 4 weeks after implantation demonstrated good device alignment and good endothelialization, but there was a tiny gap between the septal tissue and the central waist. Another animal had accidental tiny aorto-right atrial fistula. In the 11 animals that had complete VSD occlusion, the autopsy findings demonstrated good alignment of the device. At about 4 weeks after implantation, there was some endothelialization over the surface of the device, with integration of the disc and central waist to the septal tissue. There was complete endothelialization over the exposed surface of both left and right ventricular discs at 8 weeks after implantation (Figure 4). By microscopic examination, the device had tight integration onto the septal wall, with no sign of platelet aggregation or hemorrhagic accumulation of erythrocytes found on the blood-exposing side or the septal-facing side. Similarly, excellent integration of the central waist of the device was observed with the septal tissues. Good ingrowth of septal tissues was found into the interstices of the mesh wires on both discs as well as the central waist. 

Discussion

The etiology of atrioventricular block after VSD closure with the previous version of the Amplatzer VSD device is still unknown. Possible explanations may be the transmitted expansion force from the central waist or the clamping force of both discs on the conduction pathway in the nearby tissue. With this hypothesis, the new VSD device was designed to have its character of minimal expansion force around the central waist. In vitro, when we compress the central waist to a diameter smaller than its original diameter, the central waist lengthens and decreases its diameter. There is minimal expanding pressure against the compressing force. This phenomenon should also occur in vivo. After the device is deployed to close a VSD that has a smaller diameter than that of the central waist, the central waist lengthens and decreases its diameter. This device property results in less expansion force over the tissue around the VSD. With the appropriate central waist length, it also has less clamping force. According to this concept, the device should have a lower risk of atrioventricular block. In addition, both discs of this new device are designed to have good strength so that either disc can resist such high pressure in the left ventricle. This will result in good device stability and very low risk of embolization after implantation. 

In this study, we created VSD in normal heart animals instead of using the animals with clinical VSD. Prior to the study, we had tested the feasibility of VSD creation in some pig heart specimens with good result. The mean VSD diameter in this study was about 4 mm smaller than that of the balloon and the mean device size was about 2 mm larger than that of the VSD. Due to the symmetrical disc design, this device model can be deployed either from the right or the left heart. We successfully deployed the device from the left heart in the first 7 cases and from the right heart in the last 5 cases. Most of the interventricular septum in pig is muscular septum, with a very small area of membranous septum.⁸ Thus, the VSD that we created was in thick ventricular septum even when it was located in the area compatible to the perimembranous type. With the thick ventricular septum, we used devices with varying lengths (4, 7, and 10 mm) of the central waist. After deployment, the central waist was lengthened and its diameter was decreased. However, the device had a good occlusion result even with this phenomenon. We determined the suitable device size according to the VSD diameter by using the over-size device that was about 2-4 mm larger than the VSD diameter in 8 cases (pig #1-#7 and #12) and the same-size device that was equal to the VSD diameter in 4 cases (pig #8-#11). Our result included complete VSD closure in 11 cases and residual VSD in 1 case (pig #8). The residual leakage occurred in the case using the device size equal to the VSD diameter. With this device design, the closure effect is mostly from the left ventricular disc. Our data cannot conclude the appropriate selection of the device size. However, we recommend the device size about 2-3 mm larger than the VSD diameter and the central waist length nearly equal to the ventricular septal thickness. As compared to human, swine has different conducting pathway⁹ with a more vertically oriented heart.⁸ Due to the genesis of the VSD from septal balloon dilation and no evidence of abnormal electrocardiogram such as heart block during balloon dilation, we cannot determine the possibility of atrioventricular block with this study. However, this study can demonstrate the feasibility and efficacy of this new design concept for transcatheter VSD closure.

Conclusion

Transcatheter VSD closure with the new nanoplatinum-coated nitinol device in a swine model was feasible and efficacious. It provided good occlusion and endothelialization results. However, human application for perimembranous VSD closure needs further evaluation.

References

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From the ¹Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and Cardiac Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand, ²Department of Medicine, Faculty of Medicine, Chulalongkorn University and Cardiac Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand, and ³Faculty of Veterinary Science, Mahidol University, Nakhonpathom, Thailand.

Funding: This study was funded by Vascular Innovations Co Ltd, Thailand.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted April 21, 2013, provisional acceptance given May 13, 2013, final version accepted May 28, 2013.

Address for correspondence: Pornthep Lertsapcharoen, MD, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and Cardiac Center, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand. Email: lpornthep@yahoo.com