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18
COSTA ET AL.
Transition zone angles
200
180
160
140
120
100
80
Angle (degrees)
60
40
20
0
0 10203040
Proximal
Measurements
Distal
(D)
Intersection angles
200
180
160
140
120
100
Angle (degrees)
80
60
40
20
0
0 10203040
Proximal angle Distal angle
Measurements
(E)
Figure 2
(Continued)
2. Transition and intersection angles [Fig. 2(C)]:
a. Transition angles: The proximal and distal “transition” angles in non-LMCA locations
were obtuse (150.1 ±21.2 degrees and 111.3 + 29.6 degrees, respectively) [Fig. 2(D)].
b. Intersection angles: The proximal and distal “intersection” angles in non-LMCA locations
were 136.4 ± 22.0 degrees and 57.5 ± 24.7 degrees, respectively [Fig. 2(D)]. The distal intersection angle in the LMCA location (i.e., between LAD and LCX) was 68.5 ±
13.5 degrees.
3. The shape of the SB takeoff segment had a curvilinear geometry. Also, the SB ostium had an
actual elliptical shape in the majority of cases rather than a spherical shape [Fig. 2(E)].
The Intersection Between Anatomy and Physiology in Coronary Bifurcation Lesions
The physiological pattern of biological fluid diffusion through a branching system was
addressed in the classical work by C.D. Murray (11). The following are Murray’s assumptions
regarding connecting large vessels to small vessels:
(a) the cube of the radius of a mother vessel (proximal MV) should equal the sum of the cubes
of the radii of the daughter vessels (distal branches);
(b) the totalflow of thesystem is carriedby a setof vessels whoseradii cubed sum toa constant
value;
CORONARY ARTERY BIFURCATION LESIONS
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(c) under optimum physiological arrangement, flow is achieved with the least possible bio-
logical work; and
(d) a maintenance energy term is required for the volume involved.
19
Considering bifurcation lesions, Murray’s law is a function of the size of the proximal MV
and the distal branches and is represented by the following formula: D1
3
= D23+ D33(+ ...
+ ...), where D1 is the mother vessel, and D2 and D3 are the daughter vessels. Importantly,
Murray’s relation was found to be applicable to both symmetrical and asymmetrical branching
systems; also, there was no effect of lesion angulation (11,12). A study by Hutchins et al. (13)
evaluated the usefulness of the Murray’s law in predicting geometrical relationships between
MV and SB in 95 branch-points (LM =42) in postmortem human coronary arteriograms. Overall, the results validated measured diameters according to Murray’s law in angiographically
normal coronary arteries.
More recently, a study by Finet et al. (14) investigated the bifurcational fractal geometry
in 59 patients (173 bifurcations) with angiographically normal coronaries. In this seminal work,
quantitative coronary angiography (QCA) analysis was performed with a dedicated software
where each reference diameter was located in an arterial segment adjacent to the bifurcation
(mother vessel and two daughter vessels). In addition, intravascular ultrasound (IVUS) of the
LM bifurcation, LAD, and LCx was performed in 27 patients. The angles between the mother
and majordaughter vessel (proximal angle) andbetween the twodaughter vessels (distal angle)
were 156 ±29 degrees and 60 ±28 degrees, respectively. For eachbifurcation, the ratio between
the sum of the daughter-vessel diameters and the mother-vessel diameter was calculated
(ratio =Dm/Dd1+Dd2, where Dm was the diameter of themother vessel,and Dd1 and Dd2 were
the respective diameters of the two daughter vessels). Overall (n = 173), mean diameters were
3.34 ± 0.95, 2.71 ±0.77, and 2.24 ± 0.69 for Dm, Dd1,andDd2, respectively, and the mean ratio
was 0.68 ±0.066. Importantly, this ratio was constant across every scale of observation (mother
vessel diameters ranging between ≤2.5 and ≥4.5 mm), and the relative reduction between the
mother- and major daughter-vessel diameters was around 19%. Several studies have validated
Finet’s law; its applicability includes determination of actual vessel size (diameter) for the three
segments ofthe bifurcationincluding the mothervessel and two daughter vessels—iftwo diameters are known, it is possible to derive the diameter of the third vessel by using the formula
(given above) [Fig. 3(A) and 3(B)]. This may be helpful for sizing devices (balloon, stent), defining PCI strategy, and preventing complications such as coronary dissection and perforation.
Impact of Cardiac Motion on Coronary Bifurcation Lesions
Another important concept that has been largely overlooked with regard to coronary bifurcations isthe fact that thiscoronary segment is subject toconstant motion. The constantmovement
and dynamicchanges in therelationship between theMV and theSB occur continuouslyduring
the cardiac cycle (15,16). Basically, each vessel is moving in different directions and at different
time delaysas the electrical activation of theheart progresses.During the cardiac cycle, coronary
arteries follow the movement of their corresponding wall. For example, the LAD artery follows
the anterior wall, whereas the diagonal branches follow the lateral wall movement. Thus, attrition wouldbe maximizedat thebifurcation carina, wherebending andtwisting occurrepeatedly.
These constant movements may become clinically relevant if the stent is deployed through the
MV to the SB. In addition, these sustained long-term repetitive stresses may cause stent fracture or recoil or may cause excessive injury to the vessel wall. Theoretically, this may influence
long-term outcomes in this lesion subset, particularly if rigid stents are anchored in the MV, but
have to follow the 3D movement path of the distal SB.
CLASSIFICATION SCHEMES OF CORONARY BIFURCATION LESIONS
Historically, several bifurcation classification schemes have been proposed in an attempt to
standardize reporting and guide decision making [Fig. 4(A)]. However, all of the existing classifications either ignored key anatomic elements, that are essential for accurate description of
bifurcation lesions (SB ostium lesion severity and length, SB size and the myocardial territory it
supplies, angulation, tortuosity, and calcification) or were difficult to use. Although the Medina
classification distinguisheditself because it is easierto use and remember, it stilldid not address
20
COSTA ET AL.
(a)
(b)
(a)
(b)
(A)
(c)
Proximal MV
reference diameter
(d)
SB refe renc e
diameter
Distal MV referenc e diameter
(c)
(B)
Figure 3 Murray’s and Finet laws. Once the vessel diameter is known for two segments of a bifurcation, it is
possible to calculate the diameter of the third segment. (A) QCA-measured diameters at the proximal MV, distal
MV, and SB. (B) IVUS measured diameters at the proximal MV, distal MV, and SB.
the deficienciesof previous classifications (17).The Medina classificationdivides the bifurcation
lesion intothree segments: theproximal MV, thedistal MV, and the SB,and assign each segment
a binary value (1, 0) according to the presence of absence of obstruction [Fig. 4(B)]. A lesion is
designated as a “true bifurcation lesion” when both the MV and the SB have a >50% stenosis
(Medina types: 1,1,1; 1,0,1; 0,1,1) [Fig. 4(C)]. Although the Movahed classification did address
some of the deficiencies of prior classifications, it remains difficult to use (18).
Therefore, although the existing bifurcation classifications provide a basic description
of bifurcation anatomy, it does not provide sufficient anatomic information to standardize
reporting in clinical trials or to guide technical decision making. This point is clearly illustrated
Medina
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Duke
(modified)
Sanborn - - IIIIIVIIIV
Lefe´vre 2 -1434a4b
Safian IA IB IIA IIIA IIB IIIB IV
Movahed S 2L1m1sVT
Staico-Feres 3 2A 2B 2C 1A 1B 1C
DCFGABE
(A)
1,1,1 1,1,0 1,0,1 0,1,1 1,0,0 0,1,0
0,1
MB
(Distal)
,,
MB
(Proximal)
SB
0,1
0,0,1
0,1
(B)
Medina type 1,1,1 Medina type 1,0,1
Medina type 1,0,0
Medina type 1,1,0
Medina type 0,1,0
Medina type 0,1,1
(C)
Figure 4 (A) Current coronary bifurcation classifications. (B) Medina classification. (C) Examples of coronary
bifurcation lesions according to each type of the
Medina
classification.
Medina type 0,0,1
22
COSTA ET AL.
(A)
(A1) (B1) (C1)
Figure 5 “True” coronary bifurcation lesions involving the proximal LAD/Diagonal location. Note that all lesions
(A,B,C) are classified as
with a severe focal stenosis involving the SB ostium successfully treated with provisional (SB) stenting approach
(A1); B – bifurcation lesion with SB diffusely diseased unsuccessfully treated (SB occlusion) with provisional (SB)
stenting approach (B1); C – bifurcation lesion with SB diffusely diseased successfully treated with double stenting
technique (“mini-crush”), (C1).
Medina
(B) (C)
type 1,1,1; however, with different complexity and outcome: A – bifurcation lesion
in Figure 5 that shows bifurcation lesions that have similar Medina classification but clearly
different levels of complexity that require different techniques to treat.
What Are the Bifurcation Anatomic Characteristics That Affect the Frequency
and Severity of SB Compromise?
Historically, it has been suggested that SB compromise during PCI [Fig. 6(A)] is the result of
snowplowing of plaque over the SB ostium or simply “plaque shift.” However, pathologic
evaluation and IVUS studies have
quently at
the bifurcation, it is often located opposite to the flow divider, that is, opposite the
demonstrated that
although atherosclerosis develops fre-
origin of the SB. This led to the proposition that SB compromise after MV stenting is due to
“carina shift” rather than plaque shift. Nevertheless, some patients do have plaque accumulation at
the SB ostium and these patients are at high risk for plaque shift [Fig. 6(B)] (6). Although
angiographic SB compromise, even when it is >50% stenosis, is not always hemodynamically
significant when assessed physiologically (1), it can result in periproceduralischemia ormyocardial infarction when there is compromised flow. In any event, irrespective of the mechanism
that led
to SB compromise in bifurcation PCI, there are several bifurcation anatomic features
that affect the frequency and severity of this event. These features are not well represented in
the current bifurcation classifications and are as follows.
SB Size and Its Correspondent Myocardial Territory
Although the size of the SB and its correspondent myocardial territory are the most important
factors that would determine the clinical consequences of SB compromise during bifurcation
PCI, neither of these anatomic elements are represented in any of the coronary bifurcation
classifications. Furthermore, the effect of the size of myocardial territory supplied by the SB on
patient outcomes has been neither quantified nor considered in any of the studies addressing
PCI of bifurcation lesions. Although the effect of SB vessel size on procedural and long-term
outcome after bifurcation PCI is not as well defined as it relates to MV intervention, there are
several studies that did address this issue.
In general, the cutoff values for SB vessel diameters that determine inclusion or exclusion
from a specific bifurcationstudy has been arbitrary chosen in both retrospectiveregistries (19,20)
and randomized controlled trials (RCTs) (Table 1) (21–26). Of note, regardless of the technical
(a)
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(b)
(c)
(A)
(a)
(c)
(b)
(d)
(B)
Figure 6 (A)—(a) coronary bifurcation lesion with mild SB stenosis; (b) stent implantation in the MV; and (c)
SB compromise after stent implantation in the MV. (B) An example of side branches that were occluded after
angioplasty of the parent vessel in a patient with acute myocardial infarction. (a) A severe stenosis (
at the bifurcation of the middle segment of the left anterior descending artery (LAD) and the diagonal branch (Dx)
is shown in a left anterior cranial view. (b) After deployment of a stent, the diagonal branch was occluded. (c and
d) Preintervention intravascular ultrasound (IVUS) images showing diffuse plaque around the ostium of the Dx.
Source
: Adapted from Ref. 7.
arrowhead
)
24
criteria
Angiographic success
stenosis in both
branches
stenosis in both
COSTA ET AL.
branches
Criteria for SB stenting if: Actual rate
Cross-over (from single to double stenting)
bifurcation lesions
Actual rate of true
NA • Residual stenosis >50% 51.2% <50% final diameter
b
2.1% NA
(>60%), and/or
• major flow-limiting dissection
86% (16) • Severe persistent stenosis
(diffuse
b
4.3% NA
dilatation
NA • TIMI flow = 0, after SB
`
evre
31.2% <50% final diameter
and/or
94% (17) • Residual stenosis ≥50%,
b
• Dissection type B or worse,
and/or
• TIMI flow ≤2
18.8% NA
and/or
• Residual stenosis ≥75%
68% (17) • Flow limiting dissection,
3% NA
83% If after KB, SB with:
• <TIMI 3, and/or
• >70% stenosis at ostium,
and/or
• Threatened vessel closure,
and/or
• Dissection more than type A
; DES, drug-eluting stents; KB, kissing-
True bifurcation lesions
Significant stenosis in both
SB lesion was excluded)
MV and SB origin
Any bifurcation lesion type
according to Lef
classification (16)
True bifurcation lesions
and/or SB
50% stenosis of the MV
treatment
Bifurcation lesions requiring
Coronary Bifurcations: Application of the Crushing Technique Using Sirolimus-Eluting Stents
Tab le 1 Angiographic Criteria in Randomized Clinical Trials with DES in Bifurcations
Randomized
series with
DES Angiographic inclusion criteria Lesion type
bifurcation lesions
De novo
• Non-left main location
Colombo et al. (21) •
a
dominant system
• MV: ≥2.5 mm
• SB: ≥2.0 mm
bifurcation lesions
De novo
• Non-left main location
CACTUS (24) •
bifurcation lesions
De novo
• TIMI flow ≥1
• Vessel size 2.5–3.5 mm
• Lesion length ≤24 mm
Pan et al. (22) •
• Non-left main location
• MV: ≥2.5 mm
• SB: ≥2.25 mm
bifurcation lesion
De novo
• LM location allowed in a right
NORDIC (23) •
• TIMI flow ≥1 (in both branches)
• MV: 2.5–3.5 mm
a
bifurcation lesions
De novo
• SB: 2.25–3.5 mm
• Lesion length ≤28 mm
BBK (25) •
• Non-left main location
• MV: 2.5–4.0 mm
• SB: ≥2.25 mm
bifurcation lesions
De novo
•
c
BBCONE (26)
• Non-left main location
• MV: ≥2.5 mm
• SB: ≥2.25 mm
a
Lesion length criteria for each vessel of the bifurcation lesion.bDefined as ≥50% diameter stenosis in both MV and SB.
study; CACTUS,
British Bifurcation Coronary Study: Old, New, and Evolving Strategies.
Bad Krozingen Bifurcation
: BBK,
Unpublished data. BBCONE =
Abbreviations
c
balloon; MV, main vessel; NA, not available/reported; SB, side branch; TIMI, Thrombolysis in Myocardial Infarction.
CORONARY ARTERY BIFURCATION LESIONS
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Figure 7 Relationship between reference vessel diameter and SB restenosis rates in DES bifurcation series.
25
approach in treatment of bifurcations, smaller SBs appear to have increased risk of restenosis,
even with DES (Fig. 7).
More importantly, SB diameter also affectsthe risk of SBocclusion during bifurcation PCI,
where even smaller SBs may be clinically relevant (2–5). A study by Arora et al. (2) reported a
series of 167 patients including 181 bifurcations lesions presenting with SB occlusions during
PCI of the MV. In this analysis, all SBs with diameter >1.00 mm in non-LM location were
included, while lesions where the SB was protected with a wire or was treated with PCI were
excluded. In this study, 14% of patients developed postprocedure MI (new Q-wave MI and/or
three timesincrease in total CPK with elevated MBfraction within 24 hourspost-PTCA) despite
successful SB reopening in 16% of patients. In a study by Chaudhry et al. (5), 158 patients with
bifurcation lesions withSBs ≥2.00 mm were treated with singlestenting approach(MV stent). In
this study, 16% of patients had SB compromise (TIMI flow <3 and/or ≥70% stenosis); patients
with SB compromise had smaller SBs compared with those without SB compromise (2.29 ±
0.34 mm vs. 2.54 ±0.55 mm; p =0.03). Importantly, SB compromise was associated with a large
periprocedural MI (15% vs. 1.1%; p = 0.02; large AMI defined as CK-MB >5 times the upper
normal limit). Independent predictors of SB “compromise” were eccentric lesion morphology
in the MV (OR, 2.92; 95% CI, 1.11, 7.63; p = 0.03), smaller SB vessel diameter (OR, 0.21; 95% CI,
0.06, 0.77; p = 0.02), and SB% diameter stenosis (OR, 1.02; 95% CI, 1.00, 1.04; p =0.047).
SB Lesion Severity and Length
Although the Medina classification makes a distinction between SBs with > or <50% stenosis
at the ostium, it does not represent the importance of the increasing severity of the ostial SB
lesion nor it represents the importance of lesion length or the presence of more distal lesions
in the SB. Although the presence of large plaque burden at the bifurcation can be associated
with SB ostial deterioration or even occlusion after stent implantation in the MV, even in the
absence of baseline SB ostium obstruction (19) the presence of ostial SB obstruction certainly
increases this risk. Aliabadi et al. (4) categorized bifurcation lesions according to the degree of
obstruction in the SB ostium into (a) SB with minimal or no disease, where the chance of SB
occlusion was 1% to 4%; and (b) SB with ostial stenosis >50%, where the risk of SB occlusion
was
14% to 27%.Furukawa et al. demonstrated that the riskof SB deterioration (final TIMI flow
≤2) during bifurcation PCI is significantly more common in SBs with an ostial stenosis ≥50%
compared to an ostial stenosis <50% (20.8% vs. 6.1%; p =0.049) and in longer lesions compared
to shorter lesions (Fig. 8) (6). Furthermore, Chaudhry et al. (5) demonstrated that the risk for SB
26
Risk of SB
occlusion
COSTA ET AL.
p=0.003
35.0%
8.2%
SB stenosis due
to MV plaque
SB stenosis due
to SB ostium
plaque
Figure 8 Frequency of SB occlusion as a function of
SB ostium involvement.
Source
: Adapted from Ref. 6.
compromise increases with increased SB ostial stenosis severity (for every 10% increase in SB
stenosis severity, the risk of SB compromised increased by 23%) and calcification (46% vs. 26%;
p =
0.06). Therefore, it becomes clear that the lack of representation of ostial SB lesion severity
and the length in the existing classifications are major limitations to its utility in standardizing
reporting and guiding decision making.
The Bifurcation Angle
None of the existing bifurcation classifications reflect the importance of the bifurcation angle.
Although several studies have reported on measurementsof bifurcation angles (19,27,28), there
has been no standardized method, which makes comparisons between published series futile.
Lansky et al. (29) proposed a methodology for angle assessment in the Consensus Statement
from the European Bifurcation Group. This report proposed measuring two angles: (i)the
“take-off angle” (proximal angle) between the proximal MV and the SB and (ii) the “carina
angle” (distal angle) between the distal MB and the SB; to consider the widest angle in the
least foreshortened view [Fig. 9(A)]. The majority of QCA analysis software includes a “digital
caliper” tool to analyze angles and the new dedicated bifurcation QCA software has integrated
automated contour-detectors that can derive angle calculation. A study by Ramcharitar et al.
(30) reports the point ofbifurcation (POB), which isdefined as the pointwhere all the centerlines
from the three segments of the bifurcation meet (at the core of the carina); the centerlines being
the lines (or axis) through the middle of the vessel. Measurement of bifurcation angles utilizing
the angulations between the axes or the centerlines of the proximal and distal segments of the
bifurcation has beenwidely accepted. Theangle between theSB and theMV affects theoutcome
of bifurcation PCI on various levels:
r
Risk of SB compromise after MV stenting.
r
The technical easeor difficultywith whichSB wiring and stent deliverycan beaccomplished.
r
Appropriateness of coverage of the ostium SB and the extent of geometric deformation of
the SB stent.
In general, a shallow distal angle between the SB and the MV may be associated with
higher incidence of SB occlusion, especially if the SB ostium is severely diseased. However, a
shallow angle allows easier access for SB wiring and stent delivery during PCI. On the other
hand, a wider distal angle (closer to 90 degrees) may be associated with lower chances of SB
occlusion, but it may make SB wiring and stent delivery more challenging.
Bifurcation lesions have also been categorized on the basis ofthe distalangle measurement
as Y-shaped (<70 degrees) [Fig. 9(B)] or T-shaped (>70 degrees) [Fig. 9(C)]. A study by Lef`evre
et al. (19) suggested that Y-shaped lesions are associated with increased risk for periprocedural
complications compared with T-shaped lesions, including more “snow-plow” effect. Also, it
is more difficult to accurately position a stent at the SB ostium in Y-shaped bifurcations when
Angle a
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Angle b
(a)
(c)
(A)
(b)
(d)
LAD
DiagonalLAD Diagonal
(B)
Figure 9 (A) Two-dimensional angulations between the MV (LAD in this case) and the SB (Diagonal in this
case). Angle a (
between the distal MV and the SB. (B) Coronary bifurcation lesions with distal anglesmeasured 70 degrees: (a, b)
proximal LAD/Diagonal bifurcation with distal angle measured 53 degrees; (c, d) LCx/OM bifurcation with “sharp”
angle measured 35 degrees. (C) Coronary bifurcation lesions with distal angles >70 degrees: (a, b) proximal
LAD/Diagonal bifurcation with obtuse “distal” angle measured 112 degrees; (c, d) mid-LAD/Diagonal bifurcation
with distal angle measured 89 degrees.
left
) is the “take-off” angle between the proximal MV to the SB. Angle b (
right
) is the “carina angle”
(
Continued on page 28
)
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