The Sideguard Ostium Protection Device: The next generation in bifurcation stenting

Nearly 20 percent of all percutaneous coronary interventions (PCI) are performed at a bifurcation. Moreover, bifurcation and ostial lesions remain one of the more challenging coronary interventions faced by interventional cardiologists in our drug-eluting stent (DES) era. There are two schools of thought regarding how ostial and bifurcation lesions should be approached and treated. Some favor a systematic (or two-stent) approach, such as T-stenting, while others favor a provisional T-stenting (stenting the main branch first and only performing balloon angioplasty in the side branch if needed). There are issues with both approaches in terms of a satisfactory acute hemodynamic result, stent thrombosis and late restenosis (especially of the side-branch ostium). Dr. Antonio Colombo (San Raphael Hospital, Milan Italy) and colleagues have suggested that the two-stent approach, stenting both primary vessel and side branch, would minimize plaque shifting and lumen loss. However, this technique is often difficult to perform and many times results in poor stent apposition, plaque shifting (or snow plowing), and in the case of DES, interrupted drug delivery. Furthermore, the two-stent method can also cause intravascular turbulences, leading to flow velocity issues that can further lead to platelet activation and thrombus formation. Even in a DES era, restenosis rates have been observed approaching 30% when two-stent methods are used. Although the provisional stenting approach may theoretically cause less trauma to the target vessels, the lack of a second stent in the side branch leaves the ostium vulnerable to persistent stenosis or late restenosis. Additionally, plaque migration from the main vessel into the side branch often occurs, and in many cases, lesions that extend beyond the first 1-2 mm into the side vessel are not treated. Cappella Inc. (Auburndale, MA), co-founded by Dr. Antonio Colombo and Dr. Ascher Shmulewitz, has developed a unique dedicated side-branch stent for use in patients with ostial-bifurcation lesions. Cappella approaches bifurcations from a completely different angle, by first placing the Sideguard ostium protection device, a nitinol self-expanding coronary drug-eluting stent, into the side branch. It has a trumpet-shaped design, which helps the device to conform to the ostium, permitting complete stent-to-wall apposition and continuous drug delivery throughout the critical ostial transition zone. Once the Sideguard is deployed, the operator can then complete the procedure by stenting the parent vessel with any conventional drug-eluting main vessel stent. This not only perfects the result in the main vessel, but flattens the trumpet of the Sideguard completely against the main vessel wall. The procedure is completed by re-accessing the side branch through the cells of the main vessel stent, and a final kissing balloon inflation. Unlike current stenting bifurcation techniques and dedicated stenting technologies, Cappella’s Sideguard DES technology provides the operator the freedom to stent main vessels without compromising access to the side branch, and without many of the problems associated with deploying multiple stents simultaneously. This article introduces a novel stenting technology for treating ostial-bifurcation lesions and introduces a new approach that more efficiently treats side-branch ostial lesions. It will: 1. Examine the optimality of current bifurcation stenting approaches; 2. Review limitations of current main vessel stents used to treat bifurcations and dedicated bifurcation technologies; 3. Present the advantages of the Cappella approach and technology. Optimality of Current Bifurcation Approaches Many approaches have been devised to treat bifurcation lesions. Most fall short of the intended goal: preventing restenosis and repeat revascularizations. In a DES era where restenosis rates and repeat revascularization rates are below 10%, why are outcomes following bifurcation procedures so poor? The answer is likely to lie with the same techniques and technologies that are used to treat these types of lesions, which, although efficient and innovative when used in other lesions subsets, have fallen short to solve the ostial-bifurcation problem. Interventional cardiology is built on the foundation of innovation. First came balloon angioplasty, followed by coronary stents and then coronary drug-eluting stents. The problem is that interventional cardiologists have been trained to approach lesions from a target vessel perspective, no matter the location of the lesion. As a result, technology has evolved in the same fashion; the development and engineering of interventional cardiology technologies have ultimately been designed to address more conventional lesions (e.g., those found in the parent vessel). However, conventional approaches and technologies are not always optimal for the treatment of less common lesion subsets, such as bifurcations. In many cases, conventional technologies are not designed to address these types of problems, which present themselves in a small percent of the population. Most conventional technologies are developed to cater to a broader cross-section of the population. As a result, innovators are required to devise ways to adapt technologies developed for broader use and try to use them in unconventional ways. A good example is the use of balloon angioplasty to treat bifurcation lesions. Before stents were available, balloon angioplasty was used to treat bifurcation lesions. Approaches such as kissing-balloon inflation were developed and adopted. The problem was that the results following balloon angioplasty were typically disappointing, reports Dr. Thierry Lefevre (Institut Cardiovasculaire Paris Sud) in a paper published in European Cardiology in 2005.¹ Results did not improve when debulking techniques were used, such as directional or rotational atherectomy. The introduction of stents altered the way coronary lesions were treated. However, early experiences with first-generation stents in bifurcation lesions were relatively poor, notes Dr. Lefevre’s group.¹ Even today, when stents are successfully placed in both the main and side branches, problems usually arise after the procedures. These usually occur six months later and typically manifest as major adverse cardiac events (MACE) that in many cases require repeat treatment. According to Dr. Lefevre’s group, MACE rates following bifurcation angioplasty with stenting can range between 20 and 40 percent, with target vessel revascularization (TVR) rates ranging anywhere from 10 to 30 percent.¹ As a result, new stenting approaches and techniques were devised for the treatment of bifurcation lesions. Dr. Colombo’s group was one of the first to use stents in the treatment of ostial-bifurcation lesions. His group’s earliest experiences with bifurcation lesions involved the use of various stents, cutting and shaping the devices to provide scaffolding to the ostium of the side-branch. Dr. Colombo termed this part of the procedure as rebuilding the bifurcation. Other approaches involved other techniques with multiple stents.¹ These approaches include the culotte technique, simultaneous kissing stent technique, and the skirt stent technique. However, The simplest of these approaches using bare-metal stents [provisional side branch T-stenting with final kissing inflation], rapidly proved to be associated with the best…outcome, concludes Dr. Lefevre’s European Cardiology report.¹ In a separate study, Dr. Lefevre and colleagues assessed the influence of different strategies for bifurcation stenting on outcomes. For this study, Dr. Lefevre’s group enrolled over 1,100 patients. The results of this study, published in EuroIntervention in May 2005, reports a MACE rate of 18.1 percent and a TVR rate of 13.2 percent at seven months. According to his group’s analysis, non-provisional T-stenting and stenting of the side branch were predictors of MACE at seven months. Dr. Lefevre’s study concluded that provisional T-stenting…to the [side branch] is a predictor of favorable outcome after coronary bifurcation stenting using bare metal stents.² Dr. Lefevre’s study, as well as other studies, seem to point to provisional T-stenting (single stenting) as being the more favorable approach for treating bifurcations. Studies conducted by Anzuini, Al Suwaidi, Pan, Sheiban, and Assali all observed better outcomes when one stent was used over two, in terms of fewer adverse events and repeat interventions.² Functionality of Dedicated and Workhorse DES Stents for the Treatment of Bifurcations Industry has made bare metal stents tailored for bifurcations, but Dr. Colombo has noted that two problems exist with these stents: (1) they are stiff and not flexible, making them hard to deliver and (2) they are not drug-eluting and therefore, restenosis rates are high. The development of bifurcated [main vessel] stents has been virtually abandoned.¹ Dr. Lefevre conclusions regarding dedicated bifurcation stents reflect those of Dr. Colombo, indicating that the design limitations of these stents impacted profile, flexibility, and rotational ability, all of which can interfere with placement and delivery of the stent. Dr. Lefevre believes the use of non-dedicated bifurcation stents would allow continuous access to the side branch and would provide some scaffolding to the side-branch ostium, which may be a viable option.¹ Two non-dedicated bifurcation stents singled out in his European Cardiovascular report are Guidant’s MultiLink Frontier stent (Santa Clara, CA; currently in clinical trials) and Invatec’s Twin-Rail stent (Brescia, Italy). Although innovative in concept, both these stents, including some others, such as the Nile stent (Minvasys, Gennevilliers, France), which have been designed with side-branch scaffolding features, nevertheless remain main branch stents with a dual delivery system. Although both the Invatec and the Minvasys say that their bifurcation stents provide complete or optimal side-branch coverage and support, in reality both these stents would likely only provide minimal scaffolding to the side-branch ostium and are only suitable to the most acute of bifurcation angles. These stents are developed based on conventional stent designs tubular stents for use on workhorse lesions and have had their designs altered to offer side-branch access. Furthermore, none of the bifurcation stents that are currently on the market are available in a DES system. Now, with the availability of drug-eluting stents, there is a resurge [sic] in the need to have a stent to take care of both the main and the side-branches, Dr. Colombo explains. But again, it is not so easy to develop a stent which will go into the’meat’ of calcific LAD, make the turns into the circumflex, or go distally into the right [coronary artery]. He cautions that most conventional DES, which have been developed to treat workhorse lesions, are not designed to conform to the complex geometry and anatomy of lesions, such as side-branch ostial lesions. This is where conventional stents become a problem and this is the reason Dr. Colombo sees the need for either re-adopting a provisional stenting approach or developing an alternative approach to treating bifurcations. In 2004, Dr. Colombo, along with other thought-leaders from the U.S. and Europe, published in Circulation the results of a randomized study undertaken to evaluate sirolimus-eluting stents (Cypher, Cordis Corporation, a Johnson & Johnson company, Miami Lakes, FL) implanted in coronary bifurcation lesions. Six-month follow-ups revealed nearly 20 percent restenosis in the one stent arm compared to close to 30 percent restenosis in the two-stent arm.³ According to the authors of the Cypher bifurcation study, the results were not statistically different and there were improvements compared to bare-metal control studies. However, they also concluded that side-branch restenosis remained an issue of concern. Although Dr. Colombo’s group made no statement regarding the most appropriate approach (whether dual stenting or provisional stenting was most favorable) based on the non-statistically significant results of the study (20 percent restenosis in the single stenting arm compared to 30 percent restenosis in the two-stenting arm), it would appear that provisional stenting, in this case, was the most favorable approach. Furthermore, Dr. Colombo believes that DES use in the treatment of bifurcation is limited to certain lesions. He points out that Many of the [DES], which will take care of both the main-branch and the side-branch, are not so flexible and not so [easily delivered]. Although he believes that DES are appropriate in certain situations, such as bifurcations in the left main, he emphasizes that delivering DES in more complex anatomy becomes a problem. Feasibility of Approaching Bifurcation from a Completely Different Angle Dr. Colombo suggests that two solutions essentially exist for treating bifurcation lesions: (1) using one stent and adopting the provisional approach, or (2) stenting one vessel at a time. He believes that the Cappella device embraces the philosophy of stenting one vessel at a time. Conventional approaches for treating bifurcation are to stent the main branch first, try to secure the side-branch ostium using balloon techniques, and then place a second conventional DES by jailing a guidewire for placement of the second stent into the side branch. Using these methods can cause excessive trauma to the vessel walls, which can lead to thrombotic events and restenosis. Cappella approaches bifurcations from a completely different angle. Cappella’s Sideguard stent is a dedicated, self-expanding nitinol side-branch device that will deliver a drug and provide complete apposition and scaffolding to the ostium. It is delivered using a low-profile (less than 3.5 Fr), single-catheter delivery system that has no need for rotation. Dr. Colombo explains that the Sideguard can be easily delivered to the most difficult locations, such as the ostium of the side branch, because it can be navigated through very tortuous anatomy. It is not hindered by calcification in the proximal segment because the stent is shorter, flexible, and self-expanding. Dr. Colombo’s standpoint suggests a self-expanding stent provides better stent-to-vessel contact, optimizing scaffolding and drug delivery. The main issue of the two-stent bifurcation approaches, explains Dr. Donald Baim, Harvard Medical School, Boston, Massachusetts, is trying to maintain adequate lumenal geometry and wall apposition throughout the side branch, the transition zone, and the main vessel segment. Sideguard is unique because the device is self-expanding. Its design conforms to the lumenal geometry and provides continuous access to the side branch. Advantages of the Cappella Approach in the Treatment of Bifurcations One of the advantages to using the Cappella approach, according to Dr. Baim, is that the Sideguard can be placed using a conventional two-guidewire, kissing balloon technique. The Sideguard can be accurately and easily positioned at the side-branch ostium over one wire and then once deployed, any conventional coronary stent can be positioned and deployed in the parent vessel. Dr. Campbell Rogers, Harvard Medical School, Boston, Massachusetts, comments, The Cappella stent is the first system that approaches bifurcations in a compartmentalized way. The Sideguard allows the operator to treat each limb independently, as opposed to being limited to one device (e.g., the Invatec Twin-Rail stent or the Minvasys Nile stent) that supplies guidewires to both branches and can end up braiding or twisting together. Highlighting other potential advantages of the Sideguard, Dr. Rogers points to the complete coverage afforded to the ostium and carina by the stent. He attributes this to the stent’s trumpet design, which is quite different from tubular stents. Dr. Rogers refers to different studies where tubular stents have been manipulated to fit the different geometries of bifurcation and ostial lesions, reflecting sub-par results, both clinically and from a device deployment perspective. As an example, he points out poor wall apposition and struts protruding into the main branch. Dr. Rogers believes that these problems can be avoided with the Sideguard because of the Sideguard’s trumpet-shaped design. Dr. Colombo suggests that the self-expanding nature and the trumpet shape of the Sideguard provide the stent with a margin of tolerance, which means that if the stent is not exactly positioned at the side-branch ostium, the Sideguard will still conform (or hug) to the bifurcation’s anatomy. Furthermore, Dr. Colombo points to the ease of which the proximal trumpet-shaped end of the stent can be flattened against the main vessel wall once the main stent is deployed. He suggests that the Cappella device will cause less damage and trauma to the vessel walls. Performing a Sideguard Procedure Dr. Baim explains a Sideguard procedure: The procedure begins with the placement of two guidewires: one in the side branch and the other in the parent vessel. Conventional angioplasty balloons are advanced over each guidewire. This is followed by pre-dilation kissing balloon inflation. The balloon catheters are removed and the Sideguard is advanced over the side-branch guidewire. Radiopaque markers located at the distal and proximal ends of the Sideguard delivery system facilitate positioning of the stent at the side-branch ostium. The stent is deployed using a nominal pressure balloon, which helps tear a protective sheath that keeps the Sideguard in place until deployment. Once released from the special balloon-release sheath technology, the Sideguard self-expands into place. The delivery system and the guidewire are then removed from the side branch. Any conventional balloon-expandable main vessel stent is advanced over the main vessel guidewire, easily bypassing the Sideguard’s trumpet-shaped tip, and deployed into place. The procedure is completed with kissing-balloon inflation. Dr. Baim explains that the final kissing balloon inflation is performed not so much to alter the Cappella device, but to move the struts of the main vessel stent into a more circular configuration surrounding the side branch ostium. Early Experience: Animal studies Cappella has completed the majority of its animal trials and expects to initiate its first-in-man (FIM) bare-metal stent trial later this year. The Sideguard has proven itself from bench to animal trials, states Dr. Rogers. Dr. Rogers emphasizes that the Sideguard’s ease of delivery, favorable acute angiographic results, and seamless apposition (as demonstrated by both intravascular ultrasound and histology) make the Sideguard a potential alternative to current bifurcation practices and makes it an appealing platform for drug delivery. He notes that one of the drawbacks of dual delivery bifurcation systems is the possibility of wire twisting (or braiding). This braiding has become a significant problem, particularly for delivering dual-delivery stents through complex and tortuous anatomy when wire braiding may be more likely to occur. According to Dr. Rogers, although there are approaches and techniques to deal with wire braiding, having two separate or independent wires is more appealing. He suggests that treating side branches in this solitary fashion makes it much easier to perform bifurcation procedures. Once the side branch is stented, it allows the operator to stent the main branch in a more standard fashion. Dr. Baim, who was one of the principal investigators in the Sideguard animal trials, stated that both his own and Dr. Rogers’ experience in animal testing to date indicates that there is no problem with guidewire twisting, because [the Cappella approach] uses conventional two-guidewire, two-balloon kissing balloon technology. He also indicates that the Sideguard’s ease of tracking makes it very easy to place, even in the most tortuous anatomy. The Bottom Line All of the techniques to treat bifurcations using two stents, while elegant and in many cases successful, have resulted in poor long-term outcomes, states Dr. Rogers, referring to thrombotic events and restenosis at the sites of bifurcations. He comments that it remains unclear what explains these clinical failures. However, Dr. Rogers believes that it is certainly possible that the trauma to the vessel at sites where combination use of main-branch stents, employing crush technique, culotte technique and perhaps even T-stenting, may cause more damage to the carina and the bifurcation than is true elsewhere. This might set up the cascade leading up to a thrombotic event and restenosis, a reason he believes it is exciting to consider what the outcome might be in humans when a self-expanding device like the Sideguard is placed at the carina and what impact it might have in terms of decreasing the trauma to the vessel wall and lessening the cascade that follows. The Sideguard maintains good lumenal geometry throughout the bifurcated area and because it provides good wall apposition, it should reduce restenosis rates, particularly when combined with drug-eluting technology. Dr. Colombo reminds us that One of the cardinal rules of placing a stent at the ostium of a [side] branch was to dilate the [proximal end of the] stent like a trumpet. He notes that the Sideguard echoes this concept. The only different is that Sideguard already comes that way and is ready for use. No special techniques are required except for positioning the stent at the side-branch ostium, for which the Sideguard’s delivery systems comes equipped with several positioning radiopaque markers. Cappella’s Sideguard is poised to become the standard of care for ostial bifurcation lesions. The stent’s nitinol, self-expanding construction eliminates uncertainties as to stent deformation and enhances stent deliverability. The nitinol material provides unsurpassed flexibility, enabling the treatment of a wide variety of anatomical angles. Sideguard provides continuous access to the side-branch vessel, even with a main-branch stent in place. This leaves the side branch free for future stenting. More importantly, once the Sideguard is deployed, the operators can stent the parent vessel with any conventional coronary stent or DES. Adds Dr. Baim, the Sideguard ensures a graceful transition to the side-branch without obstructing normal vessel flow through the transition point. Future Developments Cappella is exploring the use of biodegradable polymer carriers for the Sideguard DES system. According to Guy Neev, Vice President, Marketing and Business Development at Cappella, the manufacturer plans to initiate its DES coating feasibility study in the near future. Cappella hopes to start its DES animal studies in late 2006. The company also anticipates initiating its FIM DES trial sometime in early 2007. This trial will incorporate the use of intravascular ultrasound to demonstrate that the Sideguard stent provides complete coverage and full apposition to the vessel wall. Cappella anticipates filing for CE Mark approval during the first half of 2008. *Graphics courtesy of Cappella Inc. SEM Photo, angiography, and IVUS images courtesy of Adam Groothuis, ECI Lab, Brigham and Women's Hospital.

1. Lefevre T, Louvard Y, Morice M-C, “Percutaneous Coronary Intervention of Bifurcation Lesions One Stent, Two Stents or a Dedicated Device, a report by, European Cardiology 2005; Reference Section.

2. Lefevre T, Morice M-C, Sengottuvel G et al., Percutaneous Influence of Technical Strategies on the Outcome of Coronary Bifurcation Stenting, EuroIntervention 2005; 1(1):31-37.

3. Colombo A, Moses J, Morice M-C et al., Randomized Study to Evaluate Sirolimus-Eluting Stents Implanted at Coronary Bifurcation Lesions, Circulation 2004; 109:1244-1249.