The Tryton Side-Branch Stent: Changing the Paradigm in Bifurcation Stenting

Bifurcation lesions are common and have been reported to make up approximately 23% of currently treated lesions. In a series capturing ‘real world’ experience with drug-eluting stents, bifurcation lesions were associated with a greater than six-fold increased risk of stent thrombosis.2 Separate studies have also shown elevated restenosis rates in the side-branch vessel as high as 28%, with a late lumen loss of 0.53 ± 0.58 mm.3,4 These rates are dramatically higher than those reported in straightforward lesions (i.e., short, non-bifurcation lesions), in which restenosis rates have been reported to occur at 4.1% with an in-stent late lumen loss of 0.17 ± 0.45 mm and in-segment late lumen loss of 0.24 ± 47 mm.5 In addition, the ability to definitively treat bifurcation lesions will be instrumental to the routine adoption of left main PCI. Provisional versus Dedicated Strategies When treating bifurcation lesions, interventionists are limited by available stents that have been designed for straight (non-bifurcation) lesions and have been optimized for deliverability, stent coverage, hoop strength and drug delivery. This limited selection forces the interventionist to choose between two primary options: provisional and dedicated approaches. Provisional Approach Using the provisional approach, the interventionist first attempts to treat the lesion with a single stent. The lesion site is prepared with balloon dilatations according to the specifics of the anatomy. A standard workhorse stent is then positioned across the side-branch origin and deployed, thereby ˜jailing’ the side-branch. The side-branch may remain ‘jailed’ or may be ‘recovered’ by introducing a wire through the deployed stent and into the side-branch. A final kiss, or simultaneous inflation of balloons positioned in both the main vessel and side-branch, is then performed. If upon completion of the procedure the interventionist is not pleased with the result, a second stent can be placed. Studies employing the provisional technique demonstrate a high crossover rate to a two-stent strategy (51.2%) and a high procedural failure rate (22.7%).4 In the minority of cases where the initial procedure is successful, long-term results have been disappointing, with target vessel failure rates of 13.6% (14.2% restenosis rate, 4.5% thrombosis rate).^3,4 T-Stenting Approach Dissatisfaction with a single stent provisional strategy has led to the development of many dedicated two-stent strategies to treat bifurcation lesions (Table 1). The simplest approach is T-stenting, where a stent is placed in the side-branch precisely at the side-branch origin, after which a main vessel stent is placed, ‘jailing’ the side-branch. Efforts are then made to re-access the side-branch through the deployed stent in order to complete the procedure with kissing balloon inflations. Despite good acute results, this approach has been shown in multiple series to be associated with high degree of restenosis. This is due to the inability to place the proximal stent edge precisely at the side-branch origin. If stent placement could be performed with the necessary precision, this approach might work well when the angle between the side-branch and main vessel is 90° but unfortunately, this is rarely the case. Even with perfect placement of stents in vessels with angles other than 90°, there will always be a portion of the carina lacking stent coverage. Crush Stenting The Crush technique, popularized by Dr. Antonio Colombo, was developed to ensure adequate stent coverage at the carina.⁶ In this technique, both side-branch and main vessel stents are positioned at the lesion site with proximal ends in the main vessel. The side-branch stent is then deployed, after which both the side-branch balloon and wire are removed. The main vessel stent is then deployed, ‘crushing’ the portion of the side-branch stent residing in the proximal main vessel. The side-branch is then re-accessed with a wire, after which a kissing balloon inflation is performed. Variants of the crush procedure the inverse, reverse and staged crush are similar in concept, but the stents are deployed in different sequence. This approach typically requires use of 7 Fr or 8 Fr guides (except for the staged crush). Furthermore, re-access of the side-branch through three layers of stents (one layer from the main vessel stent and two layers from the crushed side-branch stent) is at times is very difficult, as is passing a balloon. Published series by experienced operators demonstrate frequent failure to re-access the side-branch (>15%).⁶ This approach provided good acute angiographic results but has been associated with relatively high rates of restenosis, which typically occurs at the side-branch carina. Culotte Approach When using the culotte technique, a stent is first deployed in the main vessel, after which the side-branch is re-accessed. After ‘pre-dilatation’ of the stent side cell, a second stent is positioned with sections in both the side-branch and main vessel. The second stent is then deployed. The procedure is then completed by re-accessing the main vessel and performing a kissing balloon inflation. This procedure can be difficult at times due to the stent-stent interactions and results in complete overlap of two stent layers in the proximal main vessel segment. Evaluation of the culotte technique using bare metal stents demonstrated high rates of thrombosis and restenosis. ⁷Double Barrel Approach (AKA: Simultaneous Kissing Stents, or SKS) More recently, double barrel stenting has been advocated to treat bifurcation lesions. With this technique, stents are placed side-by-side in both the main vessel and side-branch. The proximal portions of the stents are aligned in the proximal main vessel. The stents are deployed simultaneously, using a balloon inflation protocol designed to insure maximal overlap of the stents’ sectors within the lumen. Despite requiring large guides (7, 8 Fr), this strategy is straightforward to perform in appropriate lesions. Concerns about two layers of stents within the lumen as well as the ability to re-wire specific lumens without crossing the stent-stent septum have kept this technique from being widely accepted. Both parent vessel and side-branch restenosis remain a non-trivial problem in follow-up series using the SKS technique. Nevertheless, a large series from a single center reports encouraging results. ⁸ Bifurcation-Specific Stents The poor results from both provisional and dedicated strategies have encouraged development of bifurcation-specific stents. For a device to be successful, it must have all the performance criteria of a state-of-the-art high-performance stent, including 5 Fr guide compatibility, a low profile, high trackability and complete coverage to the side-branch origin. Furthermore, designs must be able to accommodate the entire spectrum of geometries (diameters and angles) encountered in bifurcation lesions (Table 2). The majority of these efforts have focused on designing stents for the main vessel which have a side port for the side-branch origin. These technologies, such as the Petal Stent (Boston Scientific) and Frontier Stent (Guidant/Abbott Vascular), require complex delivery balloons that must track over two wires to insure proper rotational alignment. The complexity of the delivery system and concern regarding tracking performance, as well as the inability to treat all angles encountered, have slowed entry of these devices into the lab. Tryton Side-Branch Stent Technology Tryton Medical (Newton, MA) is an emerging company founded by Dr. Aaron V. Kaplan of the Dartmouth Medical School to develop stent technology to definitively treat bifurcation lesions. Tryton has focused on developing a balloon-expandable side-branch specific stent which can be wed to any standard stent. This design approach allows for a stent with (1) all the performance characteristics of a state-of-the-art stent, (2) coverage to the side-branch origin, and (3) ability to accommodate the spectrum of diameters and angles of bifurcation lesions. The Tryton Side-Branch Stent Balloon-Expandable and Side-Branch Specific The Tryton Side-Branch Stent 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) (Figure 1). ⁹ The distal side-branch region is composed of a standard stent design. (The accompanying figure has a stent with a design similar to the Bx Velocity, used in the current Cypher stents.) The central transition zone is composed of three panels designed to provide coverage to the side-branch origin and can accommodate all relevant angles. It is important to note that this design does not require rotational orientation. The proximal main vessel region is composed of long filamentous fronds, each of which is joined to the ‘wedding ban’ at the proximal stent edge. The Tryton Side-Branch Stent is pre-mounted on a balloon delivery system. Two balloon delivery systems (Standard and Stepped balloon delivery systems) are undergoing clinical evaluation. Both delivery balloons are 20 mm long. The Standard system has a nominal inflated diameter of 2.5 mm throughout its length. The Stepped delivery balloon has a distal region (2.5 mm diameter) and a proximal region (3.5 mm diameter) separated by a transition zone (4 mm length), corresponding to the regions of the Tryton Side-Branch Stent. Both stent delivery systems are low-profile systems with tracking similar to cobalt chromium stents, track over a single wire and are compatible with 5 Fr guide systems. Tryton Use The Tryton Side-Branch Stent is used in conjunction with standard interventional equipment and uses standard techniques. Typically both the side-branch and main branch segments are wired and pre-treated according to the specific anatomy and operator preference. A Tryton Side-Branch Stent is then positioned at the lesion site. Using the transition zone markers, the operator positions the Tryton Side-Branch Stent so that the distal transition zone marker is in the side-branch and the proximal transition zone marker is in the main vessel (Figure 3, Panel 1). The Tryton Side-Branch Stent is deployed at standard inflation pressures (Figure 3, Panel 2). The balloon is withdrawn while maintaining guide wire position. The side-branch guide wire is then retracted into the main branch and then advanced into the main vessel distal to the side-branch origin (Figure 3, Panel 3). The previously placed main vessel guide wire is then removed. The distal end of the main vessel stent is tracked through the proximal and transition zones of the Tryton Side-Branch Stent (Figure 3, Panel 4). The main vessel stent is deployed at standard pressures (Figure 3, Panel 5). The main vessel delivery balloon is then removed, maintaining guide wire position. The side-branch is then re-accessed with a separate wire. Side-branch access requires crossing a single layer of stent (as opposed to a crush strategy, which requires crossing three stent layers). The branch ostium is held open by the Tryton Side-Branch Stent Transition Zone, easing guide wire re-access. The procedure is then completed with a kissing balloon inflation, after which all wires and balloons are removed (Figure 3, Panel 6). Animal studies evaluating the Tryton Stent demonstrated ease-of-use as well as the ability to generate stent coverage, as presented in the schematic drawings (Figure 3). Figure 4 demonstrates necropsy evaluation of a Tryton stent placed in conjunction with a Cypher stent. The photographs confirm Tryton-main vessel stent interactions seen in the schematic drawings. Tryton Development The Tryton Side-Branch Stent is currently undergoing investigation in the Tryton First-in-Man Trial. The Tryton FIM is a multi-center trial being performed at the Heart Center/Siegburg (Prof. Eberhad Grube, Principal Investigator), the ICPS/Paris (Prof. M-C Morice, Principal Investigator) and the Thoraxcenter/Rotterdam (Prof. PWJC Serruys, Principal Investigator). As many as 30 stable patients with bifurcation lesions are being enrolled and will be followed up with a six-month angiogram and IVUS. The primary endpoint is procedural success without a major adverse cardiovascular event during hospitalization. Results are anticipated to be available during the first quarter of 2007. Tryton Technology: Future Impact Early indications are that treatment with the Tryton Side-Branch Stent provides the ability to more easily, and perhaps more definitely, treat bifurcation lesions. Standardized approaches to cardiovascular bifurcation diseases through next-generation technologies will fulfill a large unmet need in percutaneous intervention. In particular, a solution to bifurcation lesions will be instrumental to left main stenting. Disclosure: Daniel Meyer is an independent consultant. He is not an employee of Tryton and does not receive stock compensation. Dr. Carlier and Dr. Thompson have no financial conflicts of interest regarding Tryton Medical.

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