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Bifurcation Coronary Artery Disease: Current Techniques and
Future Directions (Part 2)
Overview of Dedicated Bifurcation Devices. Recent angiographic2 and intravascular ultrasound (IVUS)10 studies have convincingly demonstrated that the success of bifurcation treatment in reducing major adverse cardiac events (MACE) is dependent on the ability to consistently cover the ostium of the side branch, since the need for target lesion revascularization (TLR) of the main branch is acceptably low. The devices currently under development, specifically aimed at bifurcation disease, share a common goal of providing easy access to the side branch. They differ, however, in the degree to which they cover the side branch ostium. It is for this reason that bifurcation treatment has historically suffered from higher rates of restenosis and subsequent TLR relative to nonbifurcated lesions.2
It would appear that we are now witnessing the evolution of an industry-wide race to develop and bring to market a dedicated bifurcation device that addresses these deficiencies. Any dedicated device must fulfill several important requirements based on our understanding of the procedural challenges associated with treating bifurcations (as well as the need to consistently achieve durable long-term results).
Each bifurcation lesion has a fingerprint-like uniqueness. There is often a morphologic heterogeneity associated with bifurcations to which dedicated devices under development must invariably conform. It must be of sufficiently low profile to consistently cross what is often a complex and tortuous, calcified and nonuniform coronary milieu. In addition, there is a need to be easily integrated into the carina of the vessel, irrespective of side branch angulation and degree of calcification at the lesion site. Given these procedural complexities, any dedicated device must be associated with easeof- use, especially for the intermediate-level operator.
The unique considerations of passing standard angioplasty wires through a bifurcated vessel merits specific comment. Dedicated devices are specifically being engineered to overcome such procedural challenges as “wire wrap”. Entanglement of the wires on initial wire placement, irrespective of technique, is a well-recognized cause for primary failure of device deployment. In addition, once implanted, there is often a need to recross the limb of the bifurcation for further stent expansion or additional stent placement. Therefore, recrossing with wires and high-profile devices frequently presents a time-consuming challenge, as is often the case with the crush and cullotte techniques. The inconsistent ability to achieve, maintain and, when needed, reacquire access to the side branch are reasonable criticisms of most currentlyemployed bifurcation techniques when adequate coverage of the side branch ostium is desired.
One must draw a distinction between a true bifurcation device (which covers both limbs of the bifurcation) and those considered to be side branch access systems. Devices in the latter category may provide coverage of some portion of the parent vessel, providing only a wire or “port” to gain side branch entry. With the “true bifurcation devices”, parent-vessel coverage extends past the carina of the lesion into both limbs, essentially laying down a portion of metal not only in the main branch, but also into the side branch for a distance of several millimeters. Therefore, this contiguous track of stent coverage extends beyond the main vessel’s branch point and into the side branch. This is an appealing feature if the extent of disease requires additional side-branch stenting.
The family of bifurcation devices also includes a relative newcomer to the class, which might be considered a “parentvessel access” or “full-access” system. This device currently being studied allows stent coverage of the proximal vessel up to the carina, but does not extend preferentially down either limb of the bifurcation. It is positioned at the vessel carina, allowing equal access, with multiple wires if needed, down both branches of the vessel. The obvious concern with any device under development is the degree to which the operator may still face the daunting challenge of performing provisional stenting of the daughter vessel(s), with the inherent risk of residual gaps in the coverage of the vessel ostia. As with all new technologies, success will be judged partially on the “learning curve” required to master the device. In addition, ease-of-use in the hands of intermediate-volume, intermediate-skill operators is required for broad acceptance of a new device.
Side-Branch Access Devices and Full-Access Devices. While there are many prototypes of side-branch access systems, two representative devices in this class are Abbott Vascular’s drug-eluting Side Branch Access stent (Redwood City, California) and the YMed sideKicK™ System™(Y-Med, Inc., San Diego, California).
Formerly the Frontier System, Abbott Vascular’s drugeluting Side Branch Access (SBA) stent (Figures 10 and 11) leverages the drug, polymer and scaffolding technology of the company’s XIENCE™ V Everolimus-Eluting Coronary Stent System. The device is designed for side branch preservation utilizing a provisional T-stenting approach; this gives the operator the option of postponing the decision to stent the side branch until after the main branch is stented. A previous bare-metal version of the device was tested in the FRONTIER Registry.9 As is frequently the case in published bifurcation trials (device and technique), in the FRONTIER Registry, acute procedural complications of myocardial infarction and death in this trial were low (2.9%), and success of device implantation was greater than 90%. However, MACE rates were driven by long-term TLR (Figure 12). The binary restenosis rate for the main and side branch aggregately was 44.8%. The newest iteration of this one currently under development will be a drug-eluting device, though the basic configuration of this dual-wire, side-branch access system has not substantially changed.
The Abbott Vascular SBA stent includes a unique joining mandrel, that holds the main branch and side branch tips together, helping to avoid wire wrap, a common occurrence when advancing side-by-side angioplasty wires through a guide catheter. In addition to the joining mandrel, the device is engineered for self-rotation into proper phase at the side branch, enhancing ease-of-use and predictability. Finally, the stent is deployed with simultaneous kissing balloon inflation with one inflation device to minimize plaque shift, allowing deployment of the stent.
The technique for deployment of this device should be underscored. A SBA stent is crimped onto 2 balloons. The main branch balloon, which is mounted on a rapid-exchange lumen, extends the length of the stent. The side-branch balloon, which is mounted on an over-the-wire (OTW) lumen, exits the stent at the mid-point. Proximal to these 2 balloons, the 2 inflation lumens are joined into a single common inflation lumen that can be pressurized with a single-inflation device. The OTW lumen is occupied with a wire mandrel that exits the side-branch balloon tip and immediately enters a pocket alongside the extended main branch balloon tip, effectively joining the 2 balloon tips together. Following wiring and predilatation of both branches, the main-branch rapid-exchange (RX) balloon tip is backloaded onto the wire in the main branch. With the 2 balloon tips joined by the mandrel wire, the system is advanced to a point just proximal to the target bifurcation. The joining mandrel wire is then removed by unlocking it at the proximal adapter hub and withdrawing it from the OTW lumen. A new wire is then introduced into the OTW lumen to exit the sidebranch balloon tip and placed in the side-branch vessel. The system is then advanced into the bifurcation until forward motion stops. With a single inflation device, both the main and side branch balloons are pressurized, deploying the stent in the main branch and opening a portal into the side branch.
A somewhat similar, albeit more basic, design is the YMed sideKicK System (Figure 13). This side-branch access system allows for deployment of a stent in the main branch, with coverage extending from the proximal portion to the carina to a segment distal to the origin of the side branch. This provides adequate stent coverage of the main branch with the ability to add more stents as needed without wire removal. In addition, a wire is simply deployed through a side-branch port that runs parallel to the balloon in the main branch, affording side-branch access without providing any stent coverage in the ostium of the side branch. The most beneficial working feature of the side-port design through which the side-branch wire is passed is the amelioration of wire wrap.
Another device in the genre of parent-vessel or “fullaccess” systems is the Devax AXXESS system (Devax, Inc., Irvine, California) (Figures 14 and 15). The Devax AXXESS technology features a proprietary self-expanding nitinol stent specifically engineered for the treatment of coronary and vascular bifurcation lesions. The intent of the conical shape of this stent is to conform to the bifurcation anatomy and potentially provide “full access” to both branches for additional stenting on a provisional basis. As such, this device encircles the carina of the lesion, extending only to a minimal degree into either limb of the bifurcation.
Shaped like a “V”, with the wide end oriented distally, the stent is positioned at the level of the carina and then seated within the ostia of both branch vessels. This shape matches the anatomy of most bifurcations < 60°. With proper placement, the stent can be “deep-seated” within the lesion and actually span both vessels. Any remaining lesion (distal to the carina ) is stented provisionally, whether the residual disease is located in the main branch or the side branch.
The AXXESS stent is fabricated from a nickel titanium alloy designed to operate in the superelastic (self-expanding) phase. The self-expansion property facilitates the seating of the stent within the ostia of the branch vessels. This is meant to provide some coverage of the ostium of the side branch and is intended to simplify placement of a subsequent stent(s). Since the stent is intended to be deployed in a symmetrical fashion, presumably there is no need to orient the system within the vessel. The rapid-exchange delivery system allows the wide-mouthed distal end of the funnel-shaped stent to be deployed partially (by withdrawing a covering sheath) and accurately positioned or advanced within the vessel before it is finally released.
The stent has three highly visible radiopaque markers located at the the tip of the stent spaced approximately 120° apart to facilitate placement. These markers are also placed in such a way as to aid in accurate placement of stents in the branch vessels. A fourth marker locates the proximal part of the stent.
The stent is coated with the new limus-class drug, Biolimus A9™(Biosensors International Group Ltd.), which is currently being evaluated for use in reducing proliferation after stenting in several trials throughout the world. The drug is delivered from the abluminal surface of the stent struts using a resorbable polymer. Devax has licensed the drug Biolimus A9 and a bioabsorbable polymer coating from Occam International, an affiliate of Biosensors International.
The stent is provided in two lengths (10 and 14 mm), and diameters are intended to accommodate vessels from 2.75–4.25 mm diameter. The stent’s pyramidal shape is designed to exert a stable amount of force against the vessel wall over its stated diameter. The distal flare can expand to as much as 8 mm in the largest-diameter stent. This is what allows the device to span large bifurcation angles. A special version of the AXXESS stent designed for left main coronary artery use is under development. This stent may span bifurcations of up to 12 mm.
In the recently-reported AXXESS PLUS trial conducted at 13 international centers involving 139 patients with de novo bifurcation lesions, the 6-month composite endpoint of death, Q-wave and non-Q-wave myocardial infarction as well as TLR was < 10%. The angiographic restenosis rate in the stented side branch was 7.9%.75,76 At the time of this publication, results of a 4-center, 33-patient European left main trial are pending; it uses a newer iteration of the AXXESS design intended specifically to address the peculiarities of left main coronary bifurcation anatomy.
Main and Side Branch Stent Device. Boston Scientific Corporation is in the process of developing the Taxus® Bifurcation Stent System (Petal Device). It should be considered a “true” bifurcation device in that it is designed to pave a uniform layer of metal in the main branch as well as extending 2 millimeters into the side branch. It is the short segment stent or “nipple” extending into the side branch from which this device derives the name “Petal” (Figure 16).
The Taxus Petal™ Bifurcation Paclitaxel-Eluting Coronary Stent System has a number of unique design characteristics that merit specific comment. It is a device/drug combination product consisting of two regulated components: a device (Petal Bifurcation Coronary Stent System) and a drug (paclitaxel, slow-release) formulated in a polymer coating. The Taxus Petal Bifurcation stent is coated with a drug/polymer formulation consisting of paclitaxel (the active ingredient), and the Translute™ Polymer Carrier (the inactive ingredient).
The device component consists of the Taxus Petal Bifurcation Stent mounted onto a stent delivery system. The Taxus Petal Bifurcation stent is made of platinum-enhanced alloy. The stent consists of a main-branch stent with a positional side aperture (Petal). The Petal is positioned and deployed to provide side-branch access, coverage and support to the ostium and carina of the side-branch vessel by means of outwardly-deploying strut elements.
The stent delivery system is a dual side exchange catheter consisting of a main lumen and side branch (side sheath) lumen. The main-branch lumen guides the catheter to the lesion site, while the secondary lumen facilitates proper alignment of the Petal to the side-branch ostium. A cylindricallyshaped balloon is located at the distal end of the main lumen (main-branch balloon). A gumdrop-shaped secondary balloon (side branch balloon) is adjacent to the main-branch balloon. The Taxus Petal Bifurcation Stent is crimped over both balloons, with the side branch balloon positioned underneath the Petal elements. Upon inflation, the main-branch balloon deploys the stent into the main artery, while the side balloon deploys the Petal into the ostium of the side-branch vessel (Figures 17 and 18).
The port through which the side branch wire is advanced is useful in directing the wire into the side branch. Moreover, in the event of wire entanglement, or “wire wrap” (which could hinder device deployment), retraction of the sidebranch wire into this port generally allows the operator to disentangle the wires. Following device deployment, if the operator opts to perform provisional side-branch stenting, the Petal Bifurcation System distinguishes itself by allowing this to be accomplished without removal or further manipulation of the side-branch wire. Using high-intensity radiographic imaging in experimental beating-heart swine models, it is easy to appreciate that the extension of the Petal into the side branch helps to avoid gaps in stent coverage of the ostium and proximal side-branch segments (Figure 19).
Tryton Medical, Inc. (Boston, Massachusetts) has developed a unique device-oriented approach to the treatment of bifurcations (Figure 20). The Tryton Side Branch Stent™ system promotes a “save-the-side-branch” strategy, following a similar procedural chronology to the crush and other “side-branchfirst” techniques. As such, definitive side-branch treatment precedes main branch stenting.
The Tryton Side-Branch Stent™ is a balloon-expandable, 5 Fr guide compatible system that tracks over a single wire. It is a slotted-tube cobalt chromium stent with three distinct regions: a side-branch region (distal), a transition zone (central) and a main-vessel region (proximal). The intent of this design, is to avoid the potentially cumbersome task of rotating the catheter to achieve proper orientation. The proximal mainvessel region is composed of long filamentous fronds, each of which is joined to the “wedding band” at the proximal stent edge.
Using the transition zone markers, the Tryton Side-Branch Stent is oriented so that the distal transition zone marker is in the side branch and the proximal transition zone marker is in the main vessel. After deployment of the sidebranch stent, the balloon may be withdrawn, maintaining guidewire position. The same guidewire initially used for side-branch deployment can be retracted and advanced into the main branch, allowing for tracking of a stent through the proximal and transition zones of the Tryton Side-Branch Stent into the main branch. This device is currently undergoing clinical trials.
Conclusion
The optimal strategy for the treatment of bifurcation coronary disease has yet not been established. Over the past decade, we have witnessed significant advances in our ability to achieve durable intermediate- and long-term results in the treatment of bifurcation lesions. The tubular design of commerciallyavailable DES platforms may not appear to be an optimal choice for conforming to the architectural peculiarities of bifurcation coronary anatomy. However, improvement in bifurcation technique as well as the achievement of single-digit restenosis rates associated with drug-eluting stents have led to growing optimism regarding the percutaneous approaches to this complex lesion subset. Irrespective of the strategy employed, overwhelming data support the use of final kissing-balloon angioplasty (Figure 21).
It is clear that the industry race is on to be the first to develop a true dedicated device that will optimally address the heterogeneity of bifurcation morphologies commonly encountered by the interventional cardiologist. It will need to be user-friendly to achieve broad appeal for operators of intermediate experience. Consistent, reproducible outcome data across a spectrum of lesion morphologies must also be demonstrated if far-reaching acceptance is to be expected. However, it is conceivable that as operator expertise treating bifurcation lesions grows, and the “envelope is pushed” with current DES platforms, there may be more than just a theoretical possibility that a dedicated device will be rendered obsolete even before it comes to market.
References (continued from Part 1)
75. Costa RA, Lansky AJ, Abizaid A, et al. Long-term clinical follow-up of patients with de novo coronary bifurcation lesions treated with the nitinol self-expanding Biolimus A9-Eluting “AXXESS” stent — Results from the prospective, multicenter AXXESS Plus trial. Circulation 2006;114:18–II.
76. Costa RA, Lansky AJ, Abizaid A, et al. Long-term clinical follow-up of patients with de novo coronary bifurcation lesions treated with the nitinol self-expanding Biolimus A9-Eluting “AXXESS” stent — Results from the prospective, multicenter AXXESS Plus trial. Am J Cardiol 2006;98:8–S1
