bifurcation stenting: current strategies and new devices

doi:10.1136/hrt.2008.150391 published online 23 Sep 2008; Heart

Azeem Latib, Antonio Colombo and Giuseppe Sangiorgi

DevicesBifurcation stenting: Current Strategies and New

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1

BIFURCATION STENTING: Current Strategies and New Devices

Azeem Latib MB BCh1,2

, Antonio Colombo MD1,3

, Giuseppe M. Sangiorgi MD1,3

1) Interventional Cardiology Unit, San Raffaele Scientific Institute, Milan, Italy

2) Division of Cardiology, Department of Medicine, University of Cape Town, South

Africa

3) Interventional Cardiology Unit, EMO Centro Cuore Columbus, Milan, Italy

Running Title: Bifurcation stenting

Keywords: stents, bifurcation, coronary disease, PTCA

Address for correspondence:

Giuseppe M. Sangiorgi, MD

EMO Centro Cuore Columbus

48 Via M. Buonarroti

20145 Milan, Italy

Tel: + 39 02 4812920

Fax: + 39 02 48193433,

E-mail: [email protected]

Heart Online First, published on September 23, 2008 as 10.1136/hrt.2008.150391

Copyright Article author (or their employer) 2008. Produced by BMJ Publishing Group Ltd (& BCS) under licence.



2

Abstract

Based on the results of numerous randomized trials the, provisional approach of

implanting one stent on the main branch has become the default approach to most

bifurcation lesions. However, bifurcation intervention still remains technically

challenging. Dedicated bifurcation stents have been designed to specifically treat

coronary bifurcations with the aim of addressing some of the shortcomings of the

conventional percutaneous approach to bifurcation intervention. Majority of the

devices are aimed at facilitating the provisional approach. They are an exciting and

innovative technology that may further simplify the management and current approach

to bifurcation treatment. There are currently eleven devices available that have either

completed or are currently undergoing First-In-Man trials. The development of more

drug-eluting platforms and larger studies with control groups demonstrating their

clinical applicability, efficacy and safety are required before they are widely

incorporated into daily practice.



3

Coronary bifurcations are frequently encountered and approximately 15% to 20% of

percutaneous coronary interventions (PCI) are performed to treat bifurcations.[1] PCI

for bifurcation disease has been considered technically challenging and historically been

associated with lower procedural success rates and worse clinical outcomes than non-

bifurcation lesions. In addition there has also been large uncertainty and debate as to

the most appropriate strategy when treating bifurcations. However, in the last few years

significant improvements have occurred in our understanding and treatment of

bifurcation lesions. First, the introduction of drug-eluting stents (DES) that have

significantly reduced restenosis and repeat revascularization rates demonstrated in both

registry studies and a subanalysis of the randomized SCANDSTENT trial[2, 3]; second, a

more selective usage of two stents as intention-to-treat; third, the acceptance of a

suboptimal result in the side branch (SB) due to the fact that many residual stenosis at

the SB may not be physiologically significant[4]; fourth, the better performance of two

stent techniques associated with high pressure postdilatation, kissing inflation and

possibly intravascular ultrasound; and finally the publication of numerous randomized

controlled trials specifically in bifurcations.[1, 5, 6, 7, 8]

As a result of these changes, the outcomes after bifurcation PCI have improved

considerably and in some studies approximate those of non-bifurcation PCI.[9] There

are now 5 randomized trials[1, 5, 6, 7, 8] and a large registry[9] comparing a provisional

strategy of main branch (MB) stenting with 1DES vs. a 2DES strategy of stenting both

branches (Figure 1). From these data it is apparent that the percutaneous treatment of

coronary bifurcations has moved past an important milestone in that the one stent vs.

two stent debate appears to have been resolved. The provisional approach of

implanting one stent on the MB is now considered the default approach in most

bifurcations lesions. This approach is mainly due to the fact that routine implantation of

two stents does not give superior results compared to selective usage. Despite the

simplicity of the provisional approach, this technique frequently leaves the SB with a

significant residual stenosis (most trials evaluating the provisional approach quote

success as 30% residual on the MB and less than 50% residual on SB). The results

following implantation of two stents are sometimes suboptimal and therefore the

follow-up is inferior than expected. Operator experience, willingness to devote sufficient

time and effort to optimize the result (especially on the SB) and usage of intravascular

ultrasound are elements frequently needed when implanting two stents.[10] In our

experience a stricter adherence to this approach seems to have contributed to the

improvement seen over the last few years following implantation of two stents in

bifurcation lesions (Figure 2). However, the introduction and perfection of dedicated

bifurcation stents may simplify this task and change the current proposed approach to

bifurcation treatment. Presently routine stenting of both branches appears to offer no

advantage over a provisional approach. Based on these data a practical approach to

bifurcation PCI can be summarized as follows[11]:

1. Two guidewires should be placed in most bifurcations and the SB guidewire should

be ‘jailed’ in the majority following deployment of the stent in the MB. This

approach is important in protecting the SB from closure due to plaque shift and/or



4

stent struts during MB stenting. The guidewire jailed in the SB by the MB stent

facilitates re-wiring of the SB[12] if SB post-dilatation/stenting or final kissing balloon

inflation (FKI) is needed, or if the SB occludes. This jailed guidewire also acts as a

marker for the SB ostium and by changing the angle of SB take-off. There is usually

no need to remove the jailed guidewire during high-pressure stent dilatation in the

MB. However, it is preferable to avoid jailing hydrophilic guidewires as there is a risk

of removing the polymer coating. Accurate handling of the guiding catheter to

prevent migration into the ostium of the coronary vessel is important to allow

removal of the jailed guidewire.

2. SB provisional stenting should be the initial approach in the majority of bifurcations.

Depending on the size and importance of the SB, the provisional strategy may be

one of just trying to keep the SB open at the end of the procedure in the case of

small and/or diffusely diseased SB’s. In larger SB’s, a strategy of re-crossing the MB

stent struts to perform SB balloon angioplasty and FKI may be more appropriate.

There is no consensus as to whether FKI is mandatory when performing a provisional

strategy. However, due to the risk of dissection with FKI, it would appear prudent

that FKI be performed only on SB’s that an operator is prepared to stent if dissection

occurs.

3. Treatment of a bifurcation lesion with two stents is performed mainly as a crossover

from the provisional approach when a second stent is needed in the SB to treat a

flow-limiting dissection or a suboptimal result. Two stents as ‘intention-to-treat’

should be reserved for bifurcations with a SB that has a relatively large diameter and

territory of distribution and the following anatomical situations: disease in the SB

that extends well beyond the ostium; the SB has an unfavourable angle for re-

crossing after MB stent implantation; or the SB has a flow-limiting dissection after

predilatation. There are no solid data to support the supposition that two stents are

more thrombogenic than one – that is, provided correct stent placement has been

performed and compliance with antiplatelet therapy is maintained.[1, 9]

RATIONALE AND TYPES OF DEDICATED BIFURCATION STENTING

On the whole, irrespective of whether a one or two stent is strategy chosen, the results

after bifurcation PCI have improved if one compares the more recently published Nordic

Study[1] to previous bifurcation studies.[5, 6] If that be so, one may ask why do we even

need dedicated bifurcation stents? The conventional approach to bifurcation PCI still

has a number of limitations such as: maintaining access to SB throughout the procedure;

MB stent struts jailing the SB ostium resulting in difficulty in re-wiring SB or passing

balloon/stent into SB through the stent struts; distortion of MB stent by SB dilatation;

inability to fully cover and scaffold ostium of SB; inability of stent structure to withstand

SB balloon dilatation and deformation[13], and finally operator skills and technical

experience. Clearly bifurcation PCI is technically challenging and time consuming,

especially in order to achieve an optimal long-term result. As a result, several stents

have been specifically designed for bifurcations with the intention of addressing these

shortcomings. However, the first generation of these dedicated bifurcation stents were

difficult to deploy as they were stiff and accurate positioning of the stent at the SB



5

ostium was tricky. Many also had larger crossing profiles and less flexibility compared

with conventional stents, so that they were difficult to deliver in tortuous or calcified

arteries. It is hoped that the newer generation of bifurcation stents will overcome these

drawbacks.

The currently available (or under investigation) dedicated bifurcation stents can be

broadly divided into:

1. Stents for provisional SB stenting that facilitate or maintain access to the SB after

MB stenting and do not require re-crossing of MB stent struts (e.g. Petal™, former

AST stent, (Boston Scientific, Natick, MA, USA); Invatec Twin-Rail™ (Invatec S.r.l.,

Brescia, Italy); Antares™ (Trireme Medical Inc, CA, USA); Y-med Sidekick™ (Y-med

Inc, San Diego, CA, USA); Nile CroCo™ (Minvasys, Genevilliers, France); Multi-link

Frontier™ (Abbott Vascular Devices, Redwood City, CA/Guidant Corporation, Santa

Clara, CA, USA)). These stents allow placement of a second stent on the SB if

needed.

2. Stents that usually require another stent implanted in the bifurcation - e.g.

Sideguard™ (Cappella Inc, MA, USA); Tryton™ (Tryton Medical, MA, USA); Axxess

Plus™ (Devax, Irvine, California)). The Tryton and Sideguard are designed to treat the

SB first and require re-crossing into the SB after MB stenting for FKI. The Axxess Plus

is the exception as it is implanted in the proximal MB at the level of the carina and

does not require re-crossing into the SB but may require the additional implantation

of 2 further stents to completely treat some types of bifurcation lesions.

The stent delivery systems (SDS) of these dedicated bifurcation systems have a number

of design features in common which both explain their strengths and weaknesses:

a. Double balloon SDS have to be tracked over two wires and thus wire wrap (twisting)

is a common problem. However, the stent is implanted by simultaneous kissing

inflation possibly resulting in shorter procedure times. In addition, these devices still

tend to be bulkier than single balloon SDS requiring guide catheters larger than the

standard 6F and limiting their use in calcified lesions and tortuous vessels.

b. Stents with a preformed SB aperture maintain access to the SB during MB stenting

but successful implantation is dependent on accurate positioning with very little

tolerance for incorrect placement.

c. A SDS with a side hole needs to have axial and rotational self-positioning properties,

i.e.

− Axial: SDS has a “stopper” to position the side cell at the SB level, closest to the

carina

− Rotational: SDS automatically turns the side hole exactly towards SB

d. The Nile™, Frontier™, Twin-Rail™, Sidekick™ and Stentys™ SDS have struts that only

partially cover the ostium and thus leave the potential for a gap and ostial restenosis

e. Stents that have struts that can be expanded into SB ostium (Petal™, Ariste™) may

be clinically advantageous as they provide complete coverage of the SB orifice and

offer the possibility of delivering drug to the SB ostium

f. SB specific stents commit the operator to stenting both branches



6

g. Unfortunately, most are still BMS but with DES currently under development in the

majority.

In this review, we describe each of these devices in detail, including their unique design

features and implantation technique. The main technical characteristics have been

summarized in Table 1 and the available clinical results regarding their implantation in

humans in Table 2.



7

Table 1. Summary of the main characteristics of current dedicated bifurcation stents (Adapted from Abizaid et al[13])

GC, Guiding catheter size (French); SB, Side branch; MB, Main branch; SDS, stent delivery system; DES, drug-eluting stent

Stent type Manufacturer GC

Mechanism

of stent

expansion

Stent

material SDS

Drug-

eluted

SB

protection

Ostial SB

coverage Comments

SideKick™ Y-Med 5F Balloon-

expandable

Cobalt

Chromium

Single rapid exchange system - + +/- Partial coverage of SB ostium;

Potential SB gap when placing

second stent

Frontier™ Guidant/Abbott 7F Balloon-

expandable

Stainless

Steel

Double balloon, single wire

tracking, dual lumen tip, MB

rapid exchange & SB over-the-

wire

- + +/- Partial coverage of SB ostium;


second stent

Invatec

Twin-Rail™

Invatec 6F Balloon-

expandable

Stainless

Steel

Double balloon, dual rapid

exchange system

- + +/- Tracks over 2 wires; Partial coverage

of SB ostium; Potential SB gap when

placing second stent; No DES under

development

Nile

CroCo™

Minvasys 6F Balloon-

expandable

Cobalt

Chromium


exchange system, 2

independent catheters

- + +/- Tracks over 2 wires; Partial coverage

of SB ostium; Potential SB gap when

placing second stent; No DES under

development

SLK view™ Advanced Stent

Technology

8F Balloon-

expandable

Stainless

Steel

Single balloon, dual over-the-

wire system

- + - No coverage of SB ostium; No DES

under development

Stentys™ Stentys 7F Self-

expandable

Nitinol Single balloon, single rapid

exchange system

Paclitaxel-

PESU

polymer

- +/- Partial coverage of SB ostium;


second stent

Petal™ Boston

Scientific

7F Balloon-

expandable

Platinum

Chromium


exchange system

Paclitaxel-

Translute

polymer

+ + Tracks over 2 wires

Antares™ Trireme

Medical Inc

6F Balloon-

expandable

Stainless

Steel

Single balloon, single rapid

exchange system

- + + No DES under development

Sideguard™ Capella 6F Self-

expandable

Nitinol Single balloon, single rapid

exchange system

- N/A ++ Stenting of both branches

mandatory

Tryton™ Tryton Medical 6F Balloon-

expandable

Cobalt

Chromium

Single balloon, single rapid

exchange system

- N/A ++ Stenting of both branches

mandatory; No DES under

development

Axxess™ Devax 7F Self-

expandable

Nitinol Single wire rapid exchange

system

BiolimusA9-

PLA

polymer

+ - Requires 3 stents for complete

coverage

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Table 2. Summary of the available data and trials of current dedicated bifurcation stents

Device Study Study Type

Number of

patients/lesion

s

Follow-

up

(days)

Device

Success

(%)

Additional

stent in

MB/SB

(%)

MACE

(%)

MI

(%)

TLR

(%)

ST

(%)

Restenosis

MB (%) SB (%)

SideKick™ Solar et al[14] FIM Study 17/20 68±32 80 40* 5.8 5.8 0 5.8 N/A N/A

Frontier™ Lefevre et

al[15]

Multicenter

Registry 105 180 91 40/43 17.1 3.8 13.3 0 29.9 29.1

Invatec

Twin-Rail™

Lefevre et

al[16]

FIM Study

(DESIRE) 15 210 75 17/23 14.3 0 14.3 0 N/A N/A

Nile CroCo™ Lefevre et

al[17]

Multicenter

Registry 75 210 90.7 28/15 10.7† 2.7 6.7‡ N/A N/A N/A

SLK view™ Ikeno et al[18] Multicenter

Registry 81/84 180 97.6 14/25 31 2.5 21.3 1.3 28.3 37.7

Stentys™ PI: E. Grube[19,

20]

FIM Study

ongoing 13 30 100 15/23 0 0 0 0 N/A N/A

Petal™

AST Petal™

Ormiston et

al[21]

FIM Study 13 120 92.3 54/38 33.3 33.3 16.7 N/A 45.5 54.5

Taxus Petal™

PI: J. Ormiston

FIM Study

ongoing 45 - - - - - - - - -

Antares™ Costa et al[22] FIM Study 11 30 100 0/18 0 0 0 0 N/A N/A

Sideguard™

Grube et al[23] FIM Study

(SG-1) 20 180 80 N/A 12.5 6.3 12.5 0 N/A N/A

PI: E. Grube

Multicenter

Registry

ongoing

(SG-2)

60 - - - - - - - - -

Tryton™

Kaplan et al[24]

and Onuma et

al[25]

FIM-Study 30 180 96.7 N/A 9.9 6.6 6.6 0 4.3 0

Axxess

Plus™

Grube et al[26] Multicenter

Registry 139 180 93.5 71/52 11.2 6.0 7.5 2.2 4.8 9.2

DIVERGE

Multicenter

Registry

ongoing

600 - - - - - - - - -

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PI, Principal Investigator; FIM, First-In-Man study; MACE, Major adverse cardiac event; MI, Myocardial infarction; TLR, Target lesion

revascularization; ST, Stent thrombosis; MB: Main branch; SB: Side branch

*Not specified if MB or SB

†Follow-up data available only on 45 patients

Study reports results for Target vessel revascularization only and not TLR.

N/A: not available

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Y-med Sidekick™ (Y-med Inc, San Diego, CA, USA)

The Sidekick™ (Figure 3) is a low profile 6F guide compatible SDS that integrates a MB fixed-wire

platform with a rapid exchange steerable SB guidewire designed to preserve SB access during

bifurcation stenting. There are 3 models with different exit ports (proximal, mid, distal) that are

selected depending on the location of the disease in the bifurcation; e.g. proximal exit port for lesion

distal to bifurcation or ostial lesion. When the device is close to the carina, a guidewire is passed

through the SB exit port and MB stent struts into the SB, thus avoiding re-crossing into the SB. Various

BMS designs and even a DES platform are currently under investigation. The only clinical data

available for the Sidekick™ is unpublished data from a First-In-Man (FIM) study performed in 17

patients with 20 lesions presented at the 2007 Cardiovascular Revascularization Therapies (CRT)

conference.[14] The device success rate was 80% and an additional stent was required in 40% of

cases. During the short follow-up period (68±32 days), there was 1 major adverse cardiac event

(MACE) due to a subacute stent thrombosis.

Multilink Frontier™ (Abbott Vascular Devices, Redwood City, CA/Guidant Corporation, Santa Clara,

CA, USA)

The Multilink Frontier™ coronary stent system (Figure 4) is a balloon-expandable 316L stainless steel

stent premounted on a dedicated delivery system with two balloons (monorail for MB and over-the-

wire inner lumen for SB) and two guidewire lumens. To assist tracking and avoid guidewire crossing,

the Multilink Frontier™ has an integrated tip design that allows single tip delivery - the MB balloon tip

includes a pocket on the distal sleeve for joining the MB and SB balloon tips with a mandrel. The

Multilink Frontier™ is advanced into the MB over a conventional wire. The joining mandrel is

retracted, releasing the over-the-wire SB tip and a 300-cm wire is inserted into the SB balloon lumen

and into the SB. The system is advanced to the carina and simultaneous kissing inflation of the two

balloons is performed, using a single indeflator, to expand the stent on the MB and SB. The safety and

performance of the Multilink Frontier™ stent has been evaluated in a 105 patient multicentre

registry.[15] Device success was 91% and procedural success 93%. Reasons for failure to deliver the

device were vessel calcification in 8 cases and wire wrap in 1 case. Two patients suffered an in-

hospital myocardial infarction secondary to SB occlusion. The late loss for the Multilink Frontier™ was

0.84 ± 0.55 mm and the overall bifurcation restenosis rate (44.8%) was high (MB:29.9%, SB:29.1%). At

6-month follow-up, the target lesion revascularization (TLR) and MACE rates were 13.3% and 17.1%

respectively. There were no cases of subacute or late stent thrombosis during the follow-up period.

The next generation of the Multilink Frontier™ will be a chromium cobalt stent with the Xience V™

DES platform (i.e. Everolimus on a non-erodable acrylic and fluoro polymer).

The Invatec Twin-Rail™ (Invatec S.r.l., Brescia, Italy)

The Invatec Twin-Rail™ (Figure 5A) is a slotted tube, 316L stainless steel stent premounted on double

balloons in its proximal portion, and only on the MB balloon in its distal portion. The stent has a

closed cell type design with variable stent geometry. This 6F-compatible system consists of a single

dual lumen catheter splitting into 2 distal balloons with a central stopper that prevents further

advancement of the SDS when the carina is reached. The stent is deployed by simultaneous kissing

inflation with a single indeflator. The Twin-Rail™ is similar to the Multilink Frontier™ double-balloon

system except that in the latter the SB balloon is a short tapered balloon while in the Twin-Rail there

is a full dilatation balloon. The Twin-Rail™ double balloon SDS was evaluated in the unpublished



11

DESIRE (DoublE vs. Single balloon stent delivery systEms for bifurcation lesions) trial. This trial

presented at the Transcatheter Cardiovascular Therapeutics (TCT) 2005 meeting compared the safety

and efficacy of the Twin-Rail™ double balloon SDS (15 patients) to a single balloon SDS (24

patients).[16] Although angiographic success was high, device success was only 75% with the Twin-

Rail™ and there was a high rate of guidewire crisscross with both devices. The TLR rate for the Twin-

Rail™ was 14.3% at 7 months. In this small pilot study, there was also a trend for higher device success

and better safety profile with the Twin-Rail compared to a single balloon SDS.

Nile CroCo™ (Minvasys, Genevilliers, France)

The Nile Croco™ (Figure 5B) is a double balloon SDS similar to the Multilink Frontier™ and Twin-Rail™

but unlike these latter SDS’s that are a single catheter with single inflation port, the Nile Croco™ has

two independent yet joined catheters that require independent manipulation and pressure

monitoring. The two parallel rapid exchange catheters are premounted with a chromium cobalt stent

crimped on the MB balloon and the tip of the SB balloon. The MB balloon has 3 markers with the

central marker indicating the position of the SB aperture. After the stent is deployed into the MB, the

SB balloon is advanced into the SB and a final kissing inflation is performed. The feasibility, safety and

efficacy of bifurcation stenting using the Nile Croco™ stent is currently being evaluated in the

multicentre (10 European centers) Nile Registry.[17] Preliminary results of the first 75 patients

showed a procedural success rate of 94.7% and a MACE rate of 10.7% in the 45 patients in whom

follow-up was available at 7 months.

AST SLK-View™ (Advanced Stent Technologies, Pleasanton, CA)

The SLK-View™ (Figure 6A-B) is a 316L stainless steel flexible slotted tube stent with a side aperture

located between the proximal and distal section to facilitate access to the SB after deployment of the

stent in the MB. The delivery system has a dual over-the-wire design with a proximal dual lumen shaft

that separates into two catheters (a balloon and a side-sheath) at its distal segment. The stent is

premounted in the distal segment of delivery system with the side-sheath running under the proximal

segment of the stent and exiting through the side hole. There are total of three radiopaque markers

on the balloon, located at the centre, proximal and distal edges. The SLK-View™ system is placed over

two wires simultaneously and advanced to the bifurcation until the centre marker band is aligned to

the branch vessel and the side sheath marker separates from the centre marker. The SLK-View™ stent

is then deployed in the MB leaving the pre-formed side hole positioned at the ostium. Unlike the

Petal™ or Antares™ stents, there are no stent struts protruding into and scaffolding the ostium. The

SLK-View™ stent has been assessed in a multicenter nonrandomized study of 81 patients with 84 de

novo bifurcation lesions.[18] The study proved the feasibility of this stent with high procedural

success rates (97.6%) while maintaining SB access in all treated lesions. However, the SLK-view™ bare-

metal stent was associated with a high restenosis (MB: 28.3%, SB: 37.7%) and TLR rate (21%) at 6-

month follow-up. However, this stent has been removed from the market and is not under

investigation anymore since the company has been acquired by Boston Scientific which slightly

modified the stent creating the Petal™ stent system.

Stentys™ (Stentys S.A.S., Clichy, France)

The Stentys™ bifurcated drug-eluting stent[19] (Figure 6C) is the first of the next-generation

bifurcation stents- The Stentys™ is a self-expanding nitinol stent made of Z-shaped mesh linked by



12

small interconnections. The stent is coated on the abluminal side with Paclitaxel on a durable polymer

matrix (PESU), a polysulfone, that permits controlled drug-elution.[19, 27] The unique feature of this

stent is the ability to disconnect the stent struts with an angioplasty balloon. Thus an opening for the

SB can be created anywhere in the stent after it is implanted in the vessel while at the same time the

disconnected struts scaffold the SB ostium. Thus in comparison to the implantation of some of the

other bifurcation stents such as the Petal™ and the Antares™, the procedural success is not

dependant on accurate positioning of the stent and there is significant placement tolerance with the

Stentys™. However, it would appear from the design that the disconnected struts only partially

scaffold the ostium. The implantation procedure is performed in three steps: (1) Stentys™ is

implanted in the MB with an approximate positioning, like a standard stent; (2) optimal location for

the SB opening is chosen by inserting a balloon through the stent mesh; (3) the balloon inflation

disconnects the mesh and creates the opening. It is hoped that the self-expanding property of the

stent will allow in-situ modelling of the stent to fit the patient’s unique arterial anatomy. However, it

is not known if the Stentys™ is more prone to stent fracture due to its disconnectable strut design.

Interim results of the first 13 patients in the FIM study presented at EuroPCR 2008 demonstrated

100% procedural success.[20] In 8 patients the BMS platform of Stentys™ was implanted and in the

remaining 5 the DES version was used. Strut disconnection was possible in all stents implanted. At 30-

days, there were no adverse events in this small cohort.

Petal™ (Boston Scientific, Natick, MA, USA)

SB occlusion caused by vessel deformation and plaque shift remains a frequent problem with current

approaches to bifurcation PCI. The Petal™ stent (Figure 7 A-B), with a side aperture located mid-stent

and deployable struts (a “sleeve”) may be an attractive solution to prevent SB occlusion after MB

stenting. A guidewire is placed in the MB and another in the SB. The dual side-exchange (double

balloon) delivery system has a main lumen that guides the catheter to the primary lesion over the MB

guide wire. The secondary lumen (side sheath) facilitates proper alignment of the aperture to the SB

ostium as it tracks over the SB guidewire. In addition to a conventional cylindrical-shaped balloon,

there is a secondary elliptical balloon adjacent to the main balloon and connected to the same

inflation lumen so that a single inflation device is needed. The Petal™ stent is crimped over both

balloons such that the elliptical balloon is under the side aperture and petal elements. Upon inflation,

the main balloon deploys the stent into the MB, while the elliptical balloon deploys the petal

elements into the SB ostium The purpose of the “petal” aperture is to retain access to the SB during

and after deployment and to scaffold the SB ostium with outwardly-deploying strut elements that

extend up to 2mm into the branch during deployment. This unique feature has potential for delivery

of anti-proliferative drug to the most common site of bifurcation restenosis. The 1st

generation of this

stent, called AST Petal™, developed by Advanced Stent Technologies was a 316L stainless steel slotted

tube design. In a FIM study, the AST Petal™ was successfully implanted in 12 of 13 patients with the

one failure due to inability to advance the device after vessel dissection from predilatation.[21] Of

note in another 4 patients device delivery was temporarily impeded by wire wrap (3 cases) and

incomplete device rotation (1 case). In 9 patients an additional stent was required in the bifurcation

and the TLR rate was 15% (2/13) at 6 months. The Petal™ stent was acquired by Boston Scientific in

2004 and modified into the Taxus Petal™ stent. This 2nd

generation Petal™ stent is a platinum

chromium alloy stent which is coated with Paclitaxel on a Translute polymer [poly(styrene-b-

isobutylene-b-styrene)], which is the same polymer currently utilized by the Taxus™ stent. The



13

platinum chromium is superior to its stainless steel predecessor in that the new alloy allows even

thinner stent struts with increased flexibility and radiopacity. The Taxus Petal™ stent is currently

under investigation in a 45 patient FIM trial to assess this device’s acute performance and safety

(death, myocardial infarction, target vessel revascularization) at 30 days and 6 months, as well as

continued annual follow-up for 5 years.

Antares SAS™ (Trireme Medical Inc, CA, USA)

The Antares Sidebranch Adaptive Stent™ (SAS) with automatic SB support deployment (Figure 7 C-E)

consists of a single balloon expandable 316L stainless steel stent. It has a SB support structure in the

centre of the stent provided with radiopaque tantalum markers for positioning and orienting at the

bifurcation site. The original Antares™ system had four radiopaque tantalum markers but the current

generation system has only two markers. Stent deployment is achieved using a single rapid-exchange

balloon catheter and a SB stabilizing wire encased in a peel away lumen to minimize wire crossing. As

the stent approaches the targeted bifurcation, the catheter is torqued to align the stent central

opening with the SB ostium. The SB wire is advanced into the ostium thus assisting with accurate

placement and facilitating access after MB stent deployment. Upon expansion of the main stent body,

the ostial crown is automatically deployed with elements protruding approximately 2mm into the SB

to scaffold the ostium. The Antares™ is very similar to the Petal™ stent but has the advantage of

tracking over a single wire and unlike the Petal™ that uses a balloon to expand the SB elements; they

expand automatically with this stent. The 30-day results of the FIM study of 11 patients/lesions

treated with the Antares™ stent were presented earlier this year at the SCAI-ACCi2 summit.[22]

Device success in this small cohort was 100% and there were no adverse events in-hospital or at 30

days follow-up.

Sideguard™ (Cappella Inc, MA, USA)

The Sideguard™ ostium protection device (Figure 8A) is a self-expanding trumpet shaped nitinol stent

that is deployed using a special balloon release sheath system. It is currently a bare-metal stent but

the next generation will be drug-eluting with a biodegradable polymer. The Sideguard’s™ trumpet

shaped design helps the stent conform to the ostium allowing for complete stent-to-wall apposition,

optimizing scaffolding and drug delivery. Its short length, self-expandable nitinol system, low-profile

(less than 3.5 Fr) delivery system allows greater navigability even in very tortuous anatomy.

Radiopaque markers located at the distal and proximal ends of the Sideguard™ delivery system

facilitate positioning of the stent at the SB ostium. Sideguard™ will be indicated for bifurcation angles

from 45˚-135˚ prior to wiring. 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, the

Sideguard™ self-expands into place. The delivery system and the guidewire are then removed from

the SB. A conventional stent is then placed in the MB, the SB is re-accessed with a guidewire and the

procedure is completed with a standard FKI. The 6-month results of the first 20 patients enrolled in

the Sideguard™ FIM trial (SG-1) were presented at TCT 2007. Technical success was achieved in 16

(80%) patients. At 6-months, the TLR rate was 12.5% (2/16) and there were no cases of stent

thrombosis.[23] A second multicentre non-randomized trial has begun enrollment with the next

generation Sideguard™ device (SG-2). The new device (SG-2) has undergone minor changes to the SDS

and a major change to the stent design. The SG-2 stent has a mixed open and closed cell design with a



14

new mid-distal open cell that acts as a built-in anchoring system preventing the Sideguard™ from

migrating following deployment.

Tryton™ (Tryton Medical, MA, USA)

The Tryton™ SB stent (Figure 8B) is a slotted tube, cobalt chromium balloon expandable stent

designed to be implanted in the SB of a bifurcation. The stent consists of three zones: a distal SB zone

(that treats the disease in the SB; a transition zone (positioned at the SB ostium); and a MB zone. The

central transition zone has a specific geometry, which contains three panels, each of which can be

deformed in an independent fashion. The proximal MB zone is composed of three fronds that are

connected proximally to the transitional panel and terminate in a circumferential band and the distal

zone has the design characteristics of a standard slotted tube workhorse stent. Treatment of a

bifurcation with the Tryton™ stent generally commits the operator to implanting 2 stents in the

bifurcation and the technique is identical in approach when performing the Culotte technique. The

Tryton™ stent is deployed across the SB ostium first. The initial FIM experience has shown that

predilatation of the Tryton™ is essential to allow a MB stent to be advanced though the Tryton™

struts.[24, 25] A standard MB stent is then tracked through the proximal MB zone of the Tryton™ into

the distal MB and deployed. The MB stent struts then have to be re-crossed in order to perform a FKI.

The Tryton I FIM trial assessed the safety and performance of the Tryton™ SB stent in conjunction

with a standard DES in 30 patients.[24, 25] The Tryton™ was successfully implanted in all but 1 patient

(96.7% angiographic success) and at 6-months follow-up 3 (9.9%) patients had experienced a MACE.

Angiographic follow-up was performed in 78% of patients and demonstrated a late loss of 0.17±0.35

mm and in-segment restenosis in one patient (4.3%) in the MB proximal to the stent.

Axxess Plus™ (Devax, Irvine, California, USA)

The Axxess Plus™ stent (Figure 8C) was the first of these dedicated bifurcation stents designed to

elute an anti-restenotic drug. It delivers Biolimus-A9, a sirolimus derivative via a bio-erodable

polylactic acid polymer carrier. The Axxess Plus™ is a self-expanding, nickel-titanium, conically shaped

stent that is placed at the level of the carina. It has a rapid-exchange delivery system with hydrophilic

coating with controlled deployment upon withdrawal of a cover sheath using the actuator. However,

the Axxess™ stent may be limited by the fact that it needs to be precisely nested at the carina to be

effective and in majority cases will need another stent to fully treat the bifurcation. Grube et al have

published the results of the prospective multicenter single-arm Axxess Plus trial that enrolled 139

patients.[26] The Axxess™ stent was successfully implanted in the MB in 93.5% of cases with 80% of

the patients receiving an additional stent to the MB or SB and 42% of patients requiring 3 stents to

completely treat the bifurcation. Six of the 9 device failures were due to improper alignment when

the stent was placed distal or proximal to the intended location. At 6 months follow-up, the in-stent

late loss was 0.09±0.56mm, in-stent restenosis within the Axxess stent was 4.8% and the overall TLR

rate was 7.5%.

Preliminary Clinical Results With Dedicated Bifurcation Stents

The first generation bifurcation stents have been tested in FIM studies and multicenter registries only

(See Table 2). Although the device success was excellent with most of the devices tested, they suffer

from technical problems that may hamper acute clinical results. Restenosis rates with the first

generation devices are similar to that reported for bare metal stents in bifurcations[28] with a range



15

varying from 28% to 54% which is in turn coupled with high rates of repeat revascularization and

MACE. Second generation drug-eluting devices have only been very recently introduced and only 1

study has been published. Such experience regards the AxxessPlus™ biolimus-eluting stent which

demonstrated a favorable rate of restenosis for the MB and SB, although majority of patients required

at least one other stent implanted in the bifurcation.[26] A number of FIM studies and multicenter

registries are ongoing and the results are eagerly awaited to establish if these new devices will

become a good alternative to current bifurcation strategies in different bifurcation scenarios.

However, as has been seen with the utilisation of two stent techniques in bifurcation PCI (Figure 2),

there will be a learning curve in the optimal deployment and utilization of these new devices.

Conclusion

In conclusion, the provisional approach of implanting one stent on the MB has become the default

approach to most bifurcation lesions. However, bifurcation PCI still remains technically challenging

especially when two stent strategies are required. Dedicated bifurcation stents are an exciting

technology as they are an attempt to find specific technological solutions to a specific subset of

coronary lesions. These devices will hopefully not only improve outcomes but also simplify the

management of this complex lesion subset. Albeit that the preliminary results with the first

generation devices have been hampered by a high rate of restenosis, the development of more drug-

eluting platforms and larger studies with control groups, in the near future, will demonstrate their

true clinical applicability, efficacy and safety before they will be widely incorporated into daily

practice.



16

Funding

There are no funding sources to disclose

Competing interests

Dr Azeem Latib has no potential conflicts of interest and declares that the answer to the questions on

your competing interest form (http://bmj.com/cgi/content/full/317/7154/291/DC1) are all No and

therefore has nothing to declare.

Dr Antonio Colombo was a co-founder of Capella Inc and is a minor shareholder.

Dr Giuseppe M. Sangiorgi is a consultant for Boston Scientific.

Copyright

The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of

all authors, an exclusive licence (or non-exclusive for government employees) on a worldwide basis to

the BMJ Publishing Group Ltd and its Licensees to permit this article to be published in Heart editions

and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence

http://heart.bmjjournals.com/ifora/licence.pdf.



17

Figure Legends

Figure 1

Clinical outcomes in trials comparing a 1DES (1S) vs. 2DES (2S) strategy in treating coronary

bifurcations (p = not significant for all comparisons between 1S and 2S in all 5 trials).

MACE, major adverse cardiac events; TLR, target lesion revascularization.

Figure 2

Final Kissing Inflation, restenosis & target lesion revascularization (TLR) rates in bifurcations treated

with two drug-eluting stents (DES) at our institution over three consecutive periods. The figure

demonstrates that as our experience has increased with implanting and performing two stent

techniques with DES in a bifurcation, restenosis and TLR rates have declined.

TLR, target lesion revascularization.

Figure 3

The Y-med Sidekick™ is a fixed-wire main branch stent delivery system with different exit ports for the

side branch protection wire located either proximally (A), mid (B), or distally

Figure 4

The Multilink Frontier™ is a dual lumen, double balloon stent delivery system with the two balloons

joined by a mandrel, thus allowing tracking of the device into the main branch (MB) over a single wire

(A); when the device is close to the carina, the joining mandrel is retracted releasing the over-the-wire

side branch (SB) balloon, a guidewire is then placed via this balloon into the SB, and the entire system

is advanced to the carina (B); the stent is expanded into the MB and SB with simultaneous kissing

inflation of the two balloons using a single indeflator (C).

Figure 5

The Twin-Rail™ (A) and Nile Croco™ (B) are both double balloon, dual lumen rapid exchange systems

with the main difference being that the Nile Croco™ (B) has two independent catheters (arrows) that

can be manipulated and inflated separately.

Figure 6

The SLK-view™ is a main branch (MB) stent with a pre-formed aperture (A), without stent struts that

scaffold the ostium, that has to be positioned accurately at the ostium; the stent is mounted on a dual

over-the-wire stent delivery system that separates into a side sheath and balloon distally; the side

sheath runs under the stent and positions the side hole at the ostium (B). The Stentys™ (C) is placed in

the MB across the side branch (SB) ostium like any conventional stent and does not require accurate

placement at the ostium; a guidewire and balloon is then passed across the stent struts into the SB;

inflation of the balloon disconnects the struts and the self-expanding stent creates an opening and

scaffolds the ostium.

Figure 7

The Petal™ (A; B)and Antares™ (C; D; E) bifurcation stents both have preformed side apertures with

struts that expand into the side branch (SB) to fully cover and scaffold the SB ostium. The Petal™ is



18

mounted on a dual lumen, double balloon stent delivery system (A) with an elliptical SB balloon (black

arrow) that deploys the SB struts(B; white arrows) when both balloons are inflated by a single

indeflator. The Antares™ stent delivery system consists of a single rapid exchange balloon catheter (C)

with a SB stabilizing wire that is advanced into the SB to ensure proper alignment of the side-hole (D);

inflation of the balloon to deploy the main branch stent results in automatic expansion of the SB

elements (E).

Figure 8

The Sideguard™ (A) and Tryton™ (B) are both dedicated side branch (SB) stents. The Sideguard™ is a

self-expanding stent mounted on a low profile balloon delivery system that allows for precise delivery

of the SB stent (A). The Tryton™ SB stent consist of three zones and is positioned with the central

transition zone straddling the SB origin (B). After treating the SB with either of these devices a

conventional stent can be placed in the MB. The Axxess Plus™ stent (C) is implanted first at the level

of the carina spanning the ostia of both branching vessels, indicated by the presence of one marker in

each branch vessel which provides a reference point to guide the placement of distal stents



19

References

1 Steigen TK, Maeng M, Wiseth R, et al. Randomized study on simple versus complex stenting of

coronary artery bifurcation lesions: the Nordic bifurcation study. Circulation 2006;114:1955-61.

2 Thuesen L, Kelbaek H, Klovgaard L, et al. Comparison of sirolimus-eluting and bare metal

stents in coronary bifurcation lesions: subgroup analysis of the Stenting Coronary Arteries in Non-

Stress/Benestent Disease Trial (SCANDSTENT). Am Heart J 2006;152:1140-5.

3 Ge L, Tsagalou E, Iakovou I, et al. In-hospital and nine-month outcome of treatment of

coronary bifurcational lesions with sirolimus-eluting stent. Am J Cardiol 2005;95:757-60.

4 Koo BK, Kang HJ, Youn TJ, et al. Physiologic assessment of jailed side branch lesions using

fractional flow reserve. J Am Coll Cardiol 2005;46:633-7.

5 Colombo A, Moses JW, Morice MC, et al. Randomized study to evaluate sirolimus-eluting

stents implanted at coronary bifurcation lesions. Circulation 2004;109:1244-9.

6 Pan M, de Lezo JS, Medina A, et al. Rapamycin-eluting stents for the treatment of bifurcated

coronary lesions: a randomized comparison of a simple versus complex strategy. Am Heart J

2004;148:857-64.

7 Colombo A. CACTUS Trial (Coronary Bifurcation Application of the Crush Technique Using

Sirolimus-Eluting Stents): 6-month clinical and angiographic results. Presented at EuroPCR 2008 in

Barcelona, Spain on 13 May 2008. Available at:

http://www.europcronline.com/fo/lecture/view_slide.php?idCongres=4&id=5899. Accessed 22 July

2008.

8 Ferenc M, Buettner HJ, Bestehorn HP, et al. Bifurcations Bad Krozingen. Systematic versus

Provisional T-stenting in the Treatment of De novo Coronary Bifurcation Lesions using Sirolimus-

eEuting Stents. Presented at Transcatheter Cardiovascular Therapeutics (TCT) 2007 in Washington

D.C. on 24 October 2007. Available at:

http://www.tctmd.com/csportal/appmanager/tctmd/tct2007?_nfpb=true&_pageLabel=TCT2007Cont

ent&hdCon=1518325. Accessed 10 November 2007.

9 Tsuchida K, Colombo A, Lefevre T, et al. The clinical outcome of percutaneous treatment of

bifurcation lesions in multivessel coronary artery disease with the sirolimus-eluting stent: insights

from the Arterial Revascularization Therapies Study part II (ARTS II). Eur Heart J 2007;28:433-42.



20

10 Ge L, Iakovou I, Cosgrave J, et al. Treatment of bifurcation lesions with two stents: one year

angiographic and clinical follow up of crush versus T stenting. Heart 2006;92:371-6.

11 Latib A, Colombo A. Bifurcation Disease: What Do We Know, What Should We Do? J Am Coll

Cardiol Intv 2008;1:218-26.

12 Weinstein JS, Baim DS, Sipperly ME, et al. Salvage of branch vessels during bifurcation lesion

angioplasty: acute and long-term follow-up. Cathet Cardiovasc Diagn 1991;22:1-6.

13 Abizaid A, De Ribamar Costa J, Alfaro VJ, et al. Bifurcated stents: giving to Caesar what is

Caesar's. Eurointervention 2007;2:518-25.

14 Solar RJ. The Y Med sideKicK™ Stent Delivery System for the Treatment of Coronary Bifurcation

and Ostial Lesions. Presented at Cardiovascular Revascularization Therapies (CRT) 2007 in Washington

D.C. on 8 March 2007. Available at: http://www.crtonline.org/flash.aspx?PAGE_ID=4328. Accessed 3

December 2007.

15 Lefevre T, Ormiston J, Guagliumi G, et al. The Frontier stent registry: safety and feasibility of a

novel dedicated stent for the treatment of bifurcation coronary artery lesions. J Am Coll Cardiol

2005;46:592-8.

16 Lefevre T, on behalf of the Desire Investigators. Invatec Twin Rail Bifurcation Stent. Presented

at Transcatheter Cardiovascular Therapeutics (TCT) 2005 in Washington D.C. Available at:

http://www.tctmd.com/Show.aspx?id=68990. Accessed 22 July 2008.

17 Lefevre T, Pavlides G, on behalf of the Nile Registry investigators. Main Results of the Nile

Registry. Available at:

http://www.bifurc.net/files/medtool/webmedtool/icpstool01/stud0112/html/Nile/frame.htm.

Accessed 2 December 2007.

18 Ikeno F, Kim YH, Luna J, et al. Acute and long-term outcomes of the novel side access (SLK-

View) stent for bifurcation coronary lesions: a multicenter nonrandomized feasibility study. Catheter

Cardiovasc Interv 2006;67:198-206.

19 Laborde JC, Borenstein N, Behr L, et al. Stentys coronary bifurcation stent. Eurointervention

2007;3:162-5.



21

20 Grube E. New dedicated side branch stents. Presented at EuroPCR 2008 in Barcelona, Spain on

15 May 2008. Available at: ttp://www.europcronline.com/fo/lecture/view_slide.php?id=5898.

Accessed 22 July 2008.

21 Ormiston J, Webster M, El-Jack S, et al. The AST petal dedicated bifurcation stent: first-in-

human experience. Catheter Cardiovasc Interv 2007;70:335-40.

22 Costa RA, Abizaid A, Abizaid A, et al. Preliminary Results of the Novel TMI (TriReme Medical

Inc.) Antares Side Branch Adaptive System (Antares SASTM

Stent) for the Treatment of De Novo

Coronary Bifurcation Lesions - SCAI-ACCi2 Interventional E-Abstract 2900-123. J Am Coll Cardiol

2008;51:B51.

23 Grube E, Wijns W, Schofer J, et al. FIM Results of Cappella Sideguard™ for Treatment of

Coronary Bifurcations. Presented at Transcatheter Cardiovascular Therapeutics (TCT) 2007 in

Washington D.C. on 21 October 2007.

24 Kaplan AV, Ramcharitar S, Louvard Y, et al. Tryton I, first-in-man(FIM) study: Acute and 30 day

outcome. A preliminary report. Eurointervention 2007;3:54-9.

25 Onuma Y, Mülle R, Ramcharitar S, et al. Tryton I, first-in-man (FIM) study: six month clinical

outcome and angiographic outcome, analysis with new quantitative coronary angiography dedicated

for bifurcation lesions Eurointervention 2008;3:546-52.

26 Grube E, Buellesfeld L, Neumann FJ, et al. Six-month clinical and angiographic results of a

dedicated drug-eluting stent for the treatment of coronary bifurcation narrowings. Am J Cardiol

2007;99:1691-7.

27 Ramcharitar S, Gaster AL, Daemen J, et al. Drug-Eluting Stents, Restenosis and

Revascularization. Herz 2007;32:287-95.

28 Yamashita T, Nishida T, Adamian MG, et al. Bifurcation lesions: two stents versus one stent--

immediate and follow-up results. J Am Coll Cardiol 2000;35:1145-51.



Colombo et al5

(n=85)

Pan et al6

(n=91)

Steigen et al1

(n=413)

Ferenc et al8

(n=202)

Tsuchida et al9

(n=324)

Colombo et al7

(n=350)

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