|
|
|
 |
|
 |
 |
| Dr Antonio Colombo is
Director of the Cardiac
Catheterisation Laboratory at
EM Centro Cuore Columbus
SRL in Milan, Italy. He is an
interventional cardiologist who
has been active in the field of
coronary stenting since the early
days of this technology and has
contributed in several ways to
the improvement and refining of
various aspects of the procedure.
Dr Colombo has been the main
author and the co-author of
many publications in the area of
coronary intervention. Recently,
Dr Colombo introduced new
approaches to the treatment
of bifurcation lesions with
drug-eluting stents. |
Management of bifurcation lesions
Azeem Latib1 and
Antonio Colombo1,2
1Interventional Cardiology Unit,
San Raffaele Scientific Institute, Milan, Italy
2EMO Centro Cuore Columbus, Milan, Italy
Address for correspondence:
Antonio Colombo MD, FESC
EMO Centro Cuore Columbus SRL
Via Buonarroti 48, 20145 Milan, Italy
Tel: +39-02-4812920 Fax: +39-02-48193433
Email: info@emocolumbus.it
Abstract
Coronary bifurcations are frequently encountered by
interventional cardiologists and remain a challenging
subset of lesions to treat. Recent advances in
percutaneous coronary intervention and the introduction
of drug-eluting stents have dramatically improved our
ability to successfully treat patients percutaneously,
with improved long-term results. However, there has
been considerable controversy as to the appropriate
management strategy. This review aims to provide a
contemporary and practical approach to the percutaneous
treatment of coronary bifurcations.
Introduction
Approximately 15% to 20% of percutaneous coronary
interventions (PCI) are performed to treat coronary
bifurcations.(Ref: 1,2) Despite recent advances in interventional
cardiology and the introduction of drug-eluting stents
(DES), PCI for bifurcation remains technically challenging,
with lower procedural success rates and worse clinical
outcomes than non-bifurcation lesions.
The complexity of treating bifurcations arises not only
from the variations in bifurcation anatomy (left main,
plaque burden, angle between branches) and dynamic
changes in anatomy during treatment (plaque shift,
dissection), but also from the fact that the correct
management is more time-consuming and technically
challenging than is the case with non-bifurcation lesions.
Due to the many anatomic variants, there is no single
strategy that can be applied to every bifurcation, and
an appropriate strategy has to be tailored to each lesion
with modification if the need arises.
The management of bifurcations is a topic well suited
to the title of this journal, as considerable controversy
has surrounded the issue and there has been a lack of
consensus as to the appropriate treatment strategy. This
has predominantly stemmed from a lack of randomised
data, which may explain why therapeutic strategies have
been largely based on the personal clinical experiences of
highly skilled operators practising in high-volume centres.(Ref: 3)
In this review, we attempt to provide a practical approach
to the management of bifurcations and to highlight a few
current areas of controversy and consensus.
DES vs. BMS in bifurcations
The success of DES in reducing restenosis and
revascularisation in less complex lesions has been
extended to the coronary bifurcation.(Ref: 4) Although there
have been no randomised trials specifically comparing
bare metal stents (BMS) to DES in bifurcations, initial
registry studies from our centre have shown marked
reductions in major adverse cardiac events (MACE) and
target lesion revascularisation (TLR) rates, compared
with historical BMS controls. These reductions occurred
irrespective of whether a one-stent (MACE: 5.4% vs. 38%;
TLR: 5.4% vs. 36%) or two-stent (MACE: 13.3% vs. 51%;
TLR: 8.9% vs. 38%) strategy was used (Figure 1).(Ref: 5,6) As a
result, DES have become the preferred stent platform for
the treatment of coronary bifurcations.
 |
MACE=major adverse cardiac events; TLR=target lesion revascularisation; MB-ISR=main branch in-stent restenosis;
SB-ISR=side branch in-stent restenosis
Figure 1. Clinical and angiographic outcomes in two registry studies performed comparing a one-stent (1S) vs. two-stent (2S) approach with bare metal
(BMS) or drug-eluting stents (DES).(Ref: 5,6) |
Single vs. double stent strategy
Since the advent of stenting and the superior results it
has achieved when compared with balloon angioplasty,
there has been considerable controversy as to the optimal
strategy in bifurcation PCI. In other words, is it better
to implant a stent in the main branch only or in both
branches of the bifurcation? A practical approach to the
above problem can be summarised as follows:
1. Two wires should be placed in most bifurcations
and the side branch (SB) wire should be 'jailed' in
the majority following deployment of the stent in
the main branch (MB). This approach is important in
protecting the SB from closure due to plaque shift
and/or stent struts during MB stenting. The jailed SB
wire also facilitates re-wiring of the SB(Ref: 7) (if SB postdilatation/
stenting or final kissing balloon inflation
[FKI] is needed, or if the SB occludes) by acting as a
marker for the SB ostium and by changing the angle
of SB take-off. There is no need to remove the jailed
wire during high-pressure stent dilatation in the MB.
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
will allow removal of the jailed wire.
2. Two stents as 'intention-to-treat' should be the
technique when the disease in the SB extends beyond
the ostium and when the diameter and territory of
distribution are relatively large. 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.
3. In all other conditions, SB provisional stenting should
be the procedure of choice.
Further information on these techniques appears in the
Clinical approach to bifurcation section, below.
There are currently three published randomised trials
comparing a one-DES (1S) vs. two-DES (2S) strategy, the
results of which are summarised in Figures 2 and 3.(Ref: 1,8,9)
 |
MACE=major adverse cardiac events; TLR=target lesion revascularisation; TVR=target vessel revacularisation
Figure 2. Clinical outcomes in three randomised trials comparing a 1S vs. 2S approach in the treatment of coronary bifurcations.(Ref: 1,8,9) |
 |
| Figure 3. Angiographic restenosis in three randomised trials comparing a 1S vs. 2S approach in the treatment of coronary bifurcations.(Ref: 1,8,9) |
The Nordic Bifurcation Study,1 the largest of these
(n=413), showed no statistically significant difference in
restenosis of the bifurcation (22.5% vs. 16%, p=0.15) or
SB (19.2% vs. 11.5%, p=0.062) between the 1S vs. 2S
groups. It is interesting that this is the first bifurcation
study to show a trend towards fewer episodes of SB
restenosis in the 2S group. A strength of the study and
an explanation for the low TLR rates was that the clinical
event adjudication was performed at 6 months but
angiographic follow-up was performed later, at 8 months,
thus neutralising the effect of the oculo-stenotic reflex on
repeat revascularisation. The 2S approach, not surprisingly,
was associated with longer fluoroscopy times and larger
contrast doses. However, it must be pointed out that only
a small proportion (2%) of the lesions treated were in the
left main stem and we do not know what proportion of
the lesions treated were true bifurcations.
It is apparent from these data that routine stenting of
both branches offers no clear advantage over a provisional
strategy of stenting the MB only, with balloon angioplasty of
the SB. Thus, there appears to be consensus that a provisional
strategy is the preferred approach for the majority of
bifurcations, and that the old dictum of 'less metal is better'
still applies. The distinction between these strategies is
that, in the 1S approach, the operator is willing to accept a
suboptimal result in the SB provided TIMI (Thrombolysis in
Myocardial Infarction) flow is normal and the SB has limited
clinical relevance regarding territory of distribution.
There appears to be increasing evidence that our obsession
with trying to get the best cosmetic result in the SB
may not be physiologically important. This concept is
especially important in smaller SBs, as the majority of
angiographically significant SB lesions are not demonstrated
to be functionally significant by fractional flow reserve
analysis.(Ref: 10) Further, smaller SBs are less likely to result
in angina if a residual stenosis is left untreated or if
restenosis occurs.(Ref: 11,12) However, this should not diminish the
importance of protecting SBs with guidewires during the
procedure to prevent their closure. It has been shown that
SB (=2 mm) compromise during a provisional approach
is not inconsequential and can be associated with a large
periprocedural myocardial infarction.(Ref: 13) The 2S approach
becomes important if an optimal result and low restenosis
rates are required due to the extent of SB disease and the
clinical importance of the SB.
Clinical approach to bifurcation PCI
While the provisional strategy is the default approach
for the treatment of the majority of bifurcations, an
appropriate decision at the outset will save time and
money and reduce the risk of complications. We suggest
that there are three questions an operator needs to
answer in order to decide the appropriate primary
strategy:
1. Is it a true bifurcation - i.e. is there significant (>50%
diameter stenosis) disease in SB and MB?
2. Is the SB disease diffuse (>5 mm) and not localised to
within 3 mm of the ostium?
3. Is the SB suitable for stenting - i.e.
a. Is the SB important (does it supply a large territory
of myocardium)?
b. Is the SB ³2.5 mm in diameter?
All these factors determine the likelihood of success
with a provisional approach and whether the operator
is willing to accept a suboptimal result in the SB with
balloon angioplasty only. If the answers to all of the
above questions are yes, then the bifurcation may still be
treated with 1S but the operator should strongly consider
a 2S approach as intention-to-treat. In left main stenosis,
a 2S approach should be used almost routinely where
the bifurcation has disease in both branches, and the
provisional approach could be maintained for one branch
of a trifurcation.
Based on the response to the above three questions,
the approach to bifurcation PCI can be divided into
three strategies:
• Keep it open
• Provisional approach
• Two-stent approach
Keep it open
This strategy is utilised when the SB has ostial or diffuse
disease and is not suitable (too small) for stenting or
clinically irrelevant (see Figure 4). It is performed as
follows:
1. Wire both branches
2. Dilate MB if needed but not SB
3. Stent MB and leave wire in the SB
4. Perform post-dilatation of the MB with jailed wire
in the SB
5. Do not re-wire SB or post-dilate SB
 |
| Figure 4. An example of the 'Keep it open' strategy that we use when the SB is small and diffusely diseased. (a) baseline angiogram showing diffusely
diseased mid-to-distal right coronary artery with a true bifurcation lesion of posterior descending (PDA) and posterolateral arteries (PL); (b) guidewire
placed in MB (i.e. PDA) and SB (i.e. PL). No pre- or post-dilatation of SB after wire placement; (c) final angiographic result, after MB (PDA) successfully
stented and jailed wire in SB (PL) removed, confirming patency of SB at end of the procedure. |
This 'jailed wire' strategy allows protection of a SB
that may not require treatment but where the need
to maintain patency is important. This strategy can be
utilised as a stand-alone technique or as part of the
provisional strategy when the operator may need to
eventually dilate or stent the SB.
Provisional approach
This strategy is quick, safe, easy to perform and has
been shown to be associated with results comparable to
a more complex approach. The provisional approach is
utilised when the SB has minimal disease or disease at
the ostium only and the SB is suitable for stenting. A 6F
guide catheter is generally used but if implanting Xience
V (Abbott Vascular Devices, Redwood City, CA, USA) or
Promus™ (Boston Scientific, Natick, MA, USA), a 7F guide
is preferred. The provisional approach is performed as
follows:
1. Wire both branches
2. Pre-dilate the MB and the SB as required; many
SBs without significant disease do not require
pre-dilatation
3. Stent the MB, leaving the SB wire in place. If the
angiographic results in MB and SB are satisfactory, the
procedure is complete and the SB wire jailed behind
the MB stent struts can be removed gently
4. Re-wire SB and then remove jailed wire. In our
experience, re-crossing into the SB through the MB
stent struts is usually possible using the Rinato-
Prowater wire (Asahi Intecc Co Ltd, Nagoya, Japan/
Abbott Vascular Devices, Redwood City, CA, USA)
and in extremely difficult cases the ACE fixed wire
balloon (Boston Scientific, MA, USA). In difficult
situations, we have also successfully used the Pilot 150
(Abbott Vascular Devices, Redwood City, CA/Guidant
Corporation, Santa Clara, CA, USA) or the Miracle 3
or 4.5 gm (Asahi Intecc Co Ltd, Nagoya, Japan/Abbott
Vascular Devices, Redwood City, CA, USA) wires. The
jailed wire in the SB should always be left in place as a
marker until complete re-crossing has been done
5. SB balloon dilatation and FKI. FKI is mandatory if the
SB is dilated through the MB stent struts to correct MB
stent distortion and expansion(Ref: 14)
6. If the result remains unsatisfactory (suboptimal result,
plaque shift with >75% residual stenosis or TIMI <3, in
a SB =2.5 mm) or SB balloon dilatation is complicated
by a flow-limiting SB dissection, then perform SB
stenting (see below)
There is some uncertainty as to whether FKI is mandatory
when a provisional approach is used. Theoretically, and
from the benchmark studies, FKI has the advantage of
opening stent struts that potentially can scaffold the SB
ostium and thus facilitate future access to the SB. There
is also concern that stenting across a bifurcation without
opening the stent struts into the SB results in 'malapposed'
struts across the SB ostium that are not endothelialised.
Two-stent approach
The main difference between the 2S approach as
'intention-to-treat' or as 'crossover' from a provisional
approach is whether the SB is stented at the same
time or before the MB (in the former case) or after the
MB stent (the latter). There is a learning curve in the
treatment of bifurcations and we have found at our
institution that, as our experience with implanting two
DES in a bifurcation has increased rates of restenosis and
repeat revascularisation have decreased.(Ref: 15) Thus, we stress
that meticulous attention to performing the specific
bifurcation technique is important and improves longterm
results.(Ref: 16,17)
Intention-to-treat. When the operator decides that the
2S approach is needed as 'intention-to-treat', the guide
catheter should ideally be an 8F. The two techniques we
recommend are the V technique - when the disease does
not extend proximal to the bifurcation (less than 20% of
the time) - or the modified-T (also called mini-crush).
Performance of the V technique (Figure 5a) requires
deploying the two stents simultaneously, with some
operators performing a true simultaneous stent
deployment while others prefer to alternate balloon
inflation. However, it is important to avoid simultaneously
inflating the two stents at high pressure, a manoeuvre
which may traumatise the proximal un-stented vessel. A
practical approach is to perform the FKI with two short
non-compliant balloons, being careful not to protrude
proximally to the stents.
The modified-T or mini-crush (Figure 5b) is performed by
positioning the two stents in both branches with the SB
stent minimally protruding into the MB. The SB stent is
inflated first, and following a check for patency of the SB,
the deploying balloon and wire are removed from the SB.
The MB stent is then deployed. The final step is to re-cross
into the SB, perform a high-pressure inflation with a noncompliant
balloon in the SB (usually at 20 atm or more)
and then perform a FKI utilising another non-compliant
balloon in the MB. The FKI is also performed at high
pressure, usually 20 atm or more. This manoeuvre is called
the 'two-step kiss'.
Bench-testing of this two-step kiss technique by Dr
Ormiston's group (presented at TCT, 2006), has shown
that this technique results in improved opening of and
less obstruction by stent struts at the SB ostium.(Ref: 18)
Provisional, requiring a second stent in the SB (including
'bail-out' or 'crossover'). When there is the need to
implant a second stent in the SB, we now use the Tstenting
with protrusion technique (TAP). TAP (Figures 5c
and 6) requires advancement of a second stent in the SB
following re-crossing of the MB stent. A non-compliant
balloon is placed in the MB stent. We then pull back the SB
stent into the MB using the MB balloon as a marker. This
results in full coverage of the ostium with some minimal
protrusion. The final step is to inflate the delivery balloon
in the SB and the MB balloon at 20 atm or more. An
alternative crossover 2S technique is the reverse crush.(Ref: 16)
 |
| Figure 5. Explanatory diagrams of the V-stenting, Mini-Crush and T-stenting with protrusion techniques. Adapted from Iakovou et al. (Ref: 16) |
 |
| Figure 6. An example of the T-stenting with protrusion technique used to stent a flow-limiting dissection in the side branch after a provisional approach:
(a) baseline angiogram showing diffusely diseased left anterior descending (LAD) artery with true bifurcation lesion of LAD/diagonal; (b) plaque shift
and decreased flow in diagonal artery after stenting of LAD; (c) flow-limiting dissection in diagonal after balloon dilatation; (d) placement of Quantum™
Maverick® (Boston Scientific, Natrick, MA, USA) in LAD and Cypher® (Cordis Corporation, Miami, FL, USA) 2.5 x 18 mm stent in diagonal with slight
protrusion of stent into LAD, followed by simultaneous inflation of both balloons (black dots are balloon markers); (e) final angiographic result;
(f) intravascular ultrasound pull-back in diagonal confirming full coverage of ostium and 'figure of eight' appearance to LAD/diagonal. |
Safety of DES in bifurcation stenting
The current controversy on the safety of DES and the
risk of stent thrombosis (ST), especially in off-label
indications, has placed the use of DES in bifurcations
under the spotlight. We have previously shown that DES
implantation in bifurcations is a predictor of ST (HR 6.42;
95% CI 2.93-14.07; p<0.001) with a ST incidence of
3.5% among patients whose bifurcations were treated
with DES.19 However, the use of two stents was not an
independent predictor of ST.(Ref: 19) Further, the reported rates
of ST in some bifurcation studies are higher than seen
in less-complex lesions, although there is no uniform
definition of ST across these studies. This has raised
concerns about the safety of DES in bifurcations.
The study by Hoye et al. deepened concerns when
the authors reported a ST rate of 4.3% with the crush
technique.(Ref: 20) However, of the 10 patients who had a ST,
only two were documented angiographically and four had
discontinued dual antiplatelet therapy within 7 months of
the procedure. As this was a 2S study, the findings cannot
be extrapolated to conclude that double stenting carries a
higher risk than a single-stent strategy.
The Nordic Bifurcation Study is reassuring in that only one
patient had a definite ST and this patient was treated with
one stent.(Ref: 1) However, this study has reported 6-month
clinical data only, and it will be important to know what
the rate of ST is at 2 and 3 years. In the ARTS II study, five cases of ST (1.5%) occurred in a total of 465 bifurcations
in 324 patients treated with DES.(Ref: 4) Four of these were
sub-acute ST, with three of the bifurcation lesions having
had a poor angiographic result at the end of the procedure
and the only case of late ST occurring in a non-bifurcation
lesion. Thus, there is currently no convincing evidence
to suggest that we should refrain from using DES in
bifurcations or that a two-stent strategy is associated
with a greater risk of ST.
Despite these statements, we should take into
consideration the fact that implanting two stents always
demands more attention and expertise in order to obtain
the best result in both MB and SB. Currently, we continue
to recommend 1 year of dual antiplatelet therapy in
patients undergoing bifurcation stenting with DES.
 |
| Figure 7. A proposed approach to treat coronary bifurcations. |
Conclusions
DES have had a major impact on how we treat
complex coronary lesions and have been shown to
be more efficacious than BMS in the treatment of
bifurcations. The majority of bifurcations can be treated
with a provisional approach but there are still situations
when a 2S approach is required, either as 'intentionto-
treat' (left main or diffuse disease in SB ³2.5 mm
in diameter) or as a 'crossover' procedure from the
provisional approach (because of dissection, suboptimal
result or plaque shift). Figure 7 summarises our approach
to deciding the stenting strategy when treating a
coronary bifurcation.
Key Learning
• Bifurcations have variable anatomy and complexity, and the approach to percutaneous coronary intervention is
tailored to each lesion, based on the extent of disease, suitability for stenting and importance of the side branch
• Drug-eluting stents (DES) are more efficacious than bare metal stents and are the preferred stent platform for the
treatment of coronary bifurcations, irrespective of whether a one-stent or two-stent strategy is utilised
• A provisional strategy of stenting the main branch only is the preferred approach in the majority of bifurcations
• After treatment of bifurcations with DES, 12 months of dual antiplatelet therapy is recommended
References
1. Steigen TK, et al. Randomized study on simple versus complex stenting
of coronary artery bifurcation lesions: the Nordic bifurcation study.
Circulation 2006;114:1955-61.
2. Myler RK, et al. Lesion morphology and coronary angioplasty: current
experience and analysis. J Am Coll Cardiol 1992;19:1641-52.
3. Suzuki N, et al. Percutaneous coronary intervention of bifurcation
coronary disease. Minerva Cardioangiol 2007;55:57-71.
4. Tsuchida K, 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.
5. Yamashita T, et al. Bifurcation lesions: two stents versus one stent
- immediate and follow-up results. J Am Coll Cardiol 2000;35:1145-51.
6. Ge L, et al. In-hospital and 9-month outcome of treatment of
coronary bifurcational lesions with sirolimus-eluting stent. Am J Cardiol
2005;95:757-60.
7. Weinstein JS, et al. Salvage of branch vessels during bifurcation lesion
angioplasty: acute and long-term follow-up. Cathet Cardiovasc Diagn
1991;22:1-6.
8. Colombo A, et al. Randomized study to evaluate sirolimus-eluting stents
implanted at coronary bifurcation lesions. Circulation 2004;109:1244-9.
9. Pan M, 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.
10. Koo BK, et al. Physiologic assessment of jailed side branch lesions using
fractional flow reserve. J Am Coll Cardiol 2005;46:633-7.
11. Dauerman HL, et al. Mechanical debulking versus balloon angioplasty for the
treatment of true bifurcation lesions. J Am Coll Cardiol 1998;32:1845-52.
12. Hermiller JB. Bifurcation intervention: keep it simple. J Invasive Cardiol
2006;18:43-4.
13. Chaudhry EC, et al. Percutaneous coronary intervention for major
bifurcation lesions using the simple approach: risk of myocardial
infarction. J Thromb Thrombolysis 2007, Jan 20; Epub ahead of print.
14. Ormiston JA, et al. Drug-eluting stents for coronary bifurcations: insights
into the crush technique. Catheter Cardiovasc Interv 2004;63:332-6.
15. Latib A, et al. Impact of final kissing inflation on restenosis in coronary
bifurcations. Presented at the Eighteenth Annual Transcatheter Cardiovascular
Therapeutics Scientific Symposium, Washington DC, USA, 22-27 October 2006.
16. Iakovou I, et al. Contemporary stent treatment of coronary bifurcations.
J Am Coll Cardiol 2005;46:1446-55.
17. Ge L, et al. Clinical and angiographic outcome after implantation of drugeluting
stents in bifurcation lesions with the crush stent technique: importance
of final kissing balloon post-dilation. J Am Coll Cardiol 2005;46:613-20.
18. Ormiston JA. Reflections on Bifurcation Stent Techniques and DES
Integrity: Insights From 3D Bench Reconstructions. Presented at the
Eighteenth Annual Transcatheter Cardiovascular Therapeutics Scientific
Symposium, Washington DC, USA, 22-27 October 2006.
19. Iakovou I, et al. Incidence, predictors, and outcome of thrombosis after
successful implantation of drug-eluting stents. JAMA 2005;293:2126-30.
20. Hoye A, et al. Long-term outcomes after stenting of bifurcation lesions
with the 'crush' technique: predictors of an adverse outcome. J Am Coll
Cardiol 2006;47:1949-58. |
|
|
