Bifurcation Lesions: Challenges & Solutions
The bifurcated anatomy is highly variable and PCI of bifurcation lesions is associated with increased procedural costs, greater complication rates and worse outcomes compared with PCI of simple coronary lesions. While progress has been made, more research and consensus need to occur.

To stent or not to stent

Since the NORDIC Bifurcation and BBC One studies several years ago found similar or worse results for a two-stent (main branch and side branch) versus a one-stent approach (main branch only), the interventional community has shied away from routine stenting of the side branch in bifurcation lesions. Implanting one stent rather than two, while reserving the option to rescue the side branch, reduces procedure time and complications, and decreases the risk for in-stent restenosis and stent thrombosis. Still, questions remain.

When should the side branch be stented? Should it always be pre-dilated? What technique is best for two stents—kissing, cullote, T, crush? How should dedicated bifurcation or side branch stents be used? What is the value of intravascular ultrasound (IVUS) or fractional flow reserve (FFR)?

“There is tremendous variation in anatomy, as well as concern about how much myocardium is in jeopardy,” says Michael A. Kutcher, MD, director of interventional cardiology at Wake Forest Baptist University Medical Center in Winston-Salem, N.C. “Under the best of circumstances, there is still a high restenosis rate regardless of the technique, and bifurcation stenting with drug-eluting stents has a higher rate of stent thrombosis than in simple lesions. It’s a very hard niche of cardiology.”

In an editorial, Waksman and Bonello detailed the “nearly endless anatomic and morphologic configurations of bifurcation types” (J Am Coll Cardiol Intv 2008;1;366-368). Adding to the complexity of developing standardized protocols is the challenge in designing a clinical trial that will determine the optimal treatment strategy. “The variability in anatomy, morphology, technique and learning curve makes it almost impossible to have a reproducible and reliable trial free of deviation that can detect the preferred strategy,” they wrote.

Niemelä et al from the NORDIC Bifurcation III study, however, recently reported favorable results for main vessel stenting without final kissing balloon dilatation (FKBD) compared with FKBD (Circulation 2011;123:79-86). At six months of follow-up in the randomized trial, they found that the “simple main vessel stenting technique without FKBD provides excellent clinical results that are similar to those of the more complex strategy of main vessel stenting with FKBD.” Definite stent thrombosis was 0.4 percent in both groups, but researchers called for longer follow-up “to obtain a reliable assessment of the risk of stent thrombosis.”

Is imaging the key?

Given the lack of consensus for an optimal strategy, some operators will use IVUS, which “can be helpful in locating plaque, defining the area that needs to be treated and, additionally, in optimizing stent sizing and deployment,” says Ajay J. Kirtane, MD, an assistant professor of internal medicine in the division of cardiology at Columbia University College of Physicians and Surgeons in New York City.

IVUS utilization is relatively low and varies from operator to operator, but at Columbia, dedicated IVUS technologists make it easier to employ. Kirtane says they use IVUS in bifurcation lesions in about 30 to 50 percent of cases. Yet, there is some debate on the use of IVUS, as studies have not produced definitive data that the technique improves clinical outcomes. Some interventionalists say those studies are flawed, but the bottom line is that the data do not yet support the routine use of IVUS, Kirtane says.

Angiographic classifications of plaque location and severity are currently used, but these are rarely accurate and IVUS might be the better tool, according to Oviedo et al (Circ Cardiovasc Interv 2010;3:105-112). Researchers used IVUS to evaluate plaque distribution in left main coronary artery bifurcations and found that the disease was rarely focal and that both sides of the flow divider (carina) were always disease-free, contrary to angiography-based notions. They proposed an IVUS classification for bifurcation lesions illustrating longitudinal and circumferential spatial plaque distribution.

FFR is another technique that, since the results of the FAME trial came out in 2008, has found a small niche in bifurcation stenting. FFR uses a pressure wire to determine the hemodynamic significance of coronary lesions. Deepak L. Bhatt, MD, chief of cardiology at the VA Boston Healthcare System, uses FFR in a minority of cases. “The problem is that FFR has not been tested against the standard approach,” Bhatt says. “There are no data proving that the use of FFR in bifurcation lesions leads to better outcomes compared with angiography-guided decisions.”

The FFR pressure wire also is not as sturdy as typical workhorse wires and can have difficulty cannulating the side branch in complex bifurcations, says Issam D. Moussa, MD, from the division of cardiology at the University of Texas Health Science Center in San Antonio.

If the side branch is pinched, or jailed, after main branch stenting, however, FFR may be useful to determine whether a stent is actually needed, he says. Often, side branch lesions that are occluded immediately following main vessel stenting spontaneously recanalize on follow-up.  

Researchers have determined that plaque and carina shift, as well as stent strut movement, are the mechanisms contributing to side branch pinching. However, the contribution from each mechanism to functional significance is different. “It’s not simple,” says Bon-Kwon Koo, MD, from Stanford University in Stanford, Calif., and Seoul National University Hospital in South Korea.

Koo and colleagues studied the mechanism of geometric changes after main branch stent implantation to identify the predictors of functionally significant jailed side branch lesions (Circ Cardiovasc Interv 2010;3:113-119). They performed IVUS in the main branch and FFR in the side branch. They found that both plaque shift from the main branch and carina shift contributed to the creation and/or aggravation of a side branch ostial lesion after main branch stenting. Independent predictors of functionally significant side branch jailing were pre-intervention percent diameter stenosis of the side branch and the main vessel minimum lumen diameter located distal to the side branch ostium. These data can help inform implantation techniques, but also future design of dedicated bifurcation stents, they said.

Koo et al also found that 43 percent of the 77 side branch lesions were functionally significant, but angiography and IVUS parameters post-stenting were no different from pre-stenting. They concluded, “Anatomic evaluation does not reliably predict the functional significance of a jailed side branch stenosis.”

Dedicated bifurcation stents

The limitations of conventional bifurcation techniques include incomplete scaffolding of the side branch ostium; distortion of the main vessel stent following side branch dilation; difficulty of maintaining access to the side branch throughout the procedure; failure to wire the side branch through the main branch stent; and side branch jailing, according to Garg and Serruys (J Am Coll Cardiol 2010;56;S43-S78). A consequence of these limitations has been the development of numerous dedicated bifurcation stents.

Some of the earlier-generation complete bifurcation “Y” stents include Bard XT Carina, AVE Bifurcation, Cordis DBS and Medtronic Bifurcation Stent. These stents have had limited clinical progress because of system complexity. However, last year, Devax (now owned by Biosensors) received CE mark for its Axxess Biolimus drug-eluting “Y” stent.

There are varieties of stents that facilitate provisional side branch stenting and maintain direct access to the side branch after main vessel stenting. They include Abbott Vascular SBA, Invatec Twin-Rail, Minvasys Nile Croco (CE marked), Boston Scientific Petal, Y-med Side-kick, Stentys Bifurcation Stent (CE marked) and TriReme Medical Antaris (CE marked).

Dedicated side branch stents include Capella Sideguard (CE marked) and Tryton Medical Tryton (CE marked), which last year received FDA approval to initiate a U.S. pivotal trial.

“While our clinical outcomes are reasonably good, from an engineering and technology standpoint, there clearly is an unmet need for a safe and effective way to treat bifurcation lesions,” says Kirtane. “The sobering point is that because so many patients have acceptable outcomes with a single stent and rescue strategy, the bar is set relatively high to be able to demonstrate incremental benefits with any type of dedicated stent.”