Post on 14-Jul-2020
Integrated Use of IVUS and
FFR for LM Stenting
Gary S. Mintz, MD
Cardiovascular Research Foundation
Four studies have highlighted the inaccuracy of angiography in the
assessment of LMCA disease
• Fisher et al. Cathet Cardiovasc Diagn 1982;8:565-75
• Cameron et al. Circulation 1983;68:484-489
• Lindstaedt et al. Int J Cardiol 2007;120:254-61
• In 51 patients unanimous correct assessment of LM
severity by 4 experienced interventional cardiologists was
only 29%
• Hamilos et al. Circulation 2009;120:1505-12
• In 209 patients two reviewers either disagreed whether the
LM was significant or they agreed and were wrong in their
assessment of LM severity in 49%
IVUS vs FFR in LMCA Disease
• There is more agreement between IVUS and FFR in assessing LMCA
than in assessing non-LMCA lesions
• Limited variability in (short) LMCA length
• Limited variability in large LMCA size
• Limited variability in amount of supplied myocardium
• Both have theoretical and practical limitations
• FFR
• Proximal LAD and/or LCX disease may affect FFR of LMCA
• IVUS
• Especially in distal LMCA lesions, it is necessary to image from
both the LAD and LCX
• It is not possible to assess the LCX from an LAD-to-LM pullback,
and it is not possible to assess the LAD from an LCX-to-LM
pullback
IVUS Determinants of LMCA FFR <0.75
Jasti et al. Circulation 2004;110:2831-6
MLD MLA
CSN AS
Pe
rce
nt
Pe
rce
nt
A B
C D
0102030
405060708090
100110
1 2 3 4 5
2.8 mm
Sensitivity 93%
Specificity 98%
Sensitivity 90%
Specificity 88%
0102030
405060708090
100110
1 2 8 12 14
5.9 mm2
Sensitivity 93%
Specificity 94%
0102030
405060708090
50%
Sensitivity 86%
Specificity 80%
67%
100110
0 10 20 30 40 50 60 70 80 900
102030
405060708090
100110
20 30 40 50 60 70 80 90
4 6 10
Independent predictors for FFR (continuous
variable)• MLA (β=0.58, 95% CI=0.02-0.04, p<0.001)
• Plaque rupture (β=-0.24, 95% CI= -0.09-0.01, p=0.036)
IVUS determinants of LM FFR (n=47)
Sensitivity 83%
Specificity 83%
PPV 83%
NPV 83%
Accuracy 83%
0 20 40 60 80 100
100-Specificity
100
80
60
40
20
0
Sen
sit
ivit
y
MLA predicting FFR<0.80
Sensitivity 78%
Specificity 75%
PPV 75%
NPV 78%
Accuracy 77%
PB predicting FFR<0.80
0 20 40 60 80 100
100
80
60
40
20
0
Sen
sit
ivit
y
100-Specificity
Cut-off=72%AUC=0.77
95% CI=0.62-0.88
Cut-off=4.8mm2
AUC=0.89
95% CI=0.76-0.96
Kang et al. JACC Cardiovasc Interv 2011;4:1168-74
Men Women
South Korea 68.6 kg 56.5 kg
US 88.3 kg 74.7 kg
Heart weight correlates directly with body weight (r=0.8-0.9)
Kang et al. JACC Cardiovasc Interv 2011;4:1168-74Yoon et al. Korean J Path 1999;33:1-8
Seo et al. J Korean Med Sci 2000;15:641-6
Plaque rupture
No rupture
10.08.06.04.02.00
1.0
0.9
0.8
0.7
0.6
FFR
MLA (mm2)
Asia US
• An in vitro model suggests that
positioning the FFR guidewire in the
LCX will not accurately reflect the
LMCA only if the composite FFR in
the LMCA+LAD is ≤0.65.
• An in vivo ovine model suggests that
an FFR in the uninvolved artery will
not accurately reflect the LMCA only
if the composite FFR in the LMCA+the
involved artery is ≤0.50 and that an
FFR >0.85 would indicate that the
LMCA is not functionally significant.
Ragosta et al. Catheter Cardiovasc Interv 2006;67:357-72Capodanno et al. JACC Cardiovasc Interv 2009;2:731-8
Daniels et al. JACC Cardiovasc Interv 2012;5:1021-5Young et al. Circ Cardiovasc Interv 2013, in press
LMCA disease is rarely isolated (6-9%)
0 1.0 4.0mm
0 1.0 5.0mm
LCX
LAD
• In 25% of patients, MLA differs by 1mm2 when
imaged from a pullback beginning in the LAD
vs the LCX.
• Since IVUS can artificially increase, but not
decrease lumen dimensions, the smallest MLA
is always the most accurate
Sensitivity Specificity
Plaque
burden
>40%
59% 45%
Plaque
burden
>70%
78% 42%
Evaluation of the LAD
from the LM-LCX
pullback
Sensitivity Specificity
Plaque
burden
>40%
67% 55%
Plaque
burden
>70%
88% 42%
Evaluation of the LCX
from the LM-LAD
pullback
Oviedo et al. Am J Cardiol 2010;105:948-54
Dif
fere
nce b
etw
een
esti
mate
d a
nd
dir
ectl
y
measu
red
lu
men
dia
mete
rs (
mm
)1
0
-1
-2
-3
+2SD
-2SD
Dif
fere
nce b
etw
een
esti
mate
d a
nd
dir
ectl
y
measu
red
lu
men
dia
mete
rs (
mm
)
1
0
-1
-2
-3
+2SD
-2SD
LCX
LCX
LCX
LCX
LCX (1)LAD (1)
LMCA (1/1)
62% 14% 14%
4% 3% 2% 1%
LCX (1)LAD (1) LCX (0)LAD (1)
LCX (1)LAD (1) LCX (0)LAD (1) LCX (1)LAD (1) LCX (1)LAD (0)
LMCA (1/0) LMCA (1/0)
LMCA (0/1) LMCA (0/0) LMCA (0/0) LMCA (0/1)
1/1,1,1 1/0,1,1 1/0,1,0
0/1,1,1 0/0,1,0 0/0,1,1 0/1,0,1
IVUS plaque distribution in 140 distal LMCA
bifurcation lesions
Oviedo et al. Circ Cardiovasc Interv. 2010;3:105-12
0% 100%
Medina 1,1,1(n=21)
Medina 1,1,0(n=9)
Medina 1,0,1(n=6)
Medina 0,1,1(n=11)
Medina 1,0,0(n=7)
Medina 0,1,0(n=14)
Medina 0,0,1(n=12)
Medina 0,0,0(n=60)
All lesions(n=80)
Others
Oviedo et al. Circ Cardiovasc Interv. 2010;3:105-12
Ostial LAD @ Carina
Distal LMCA
LAD
LCX
LAD
LCX
Ostial LCX @ Carina
Hamilos et al. Circulation 2009;120:1505-1512
FFR ≥ 0.8 managed medically
FFR <0.8 managed surgically
P=0.5
FFR ≥ 0.8 managed medically
FFR <0.8 managed surgically
P=0.5
• A RCA stenosis was the sole independent predictor for MACE.
• MACE survival rates at 5 years in the medical and surgical groups
were 70% and 66%, respectively, P=0.54.
Outcomes in 136 pts with an FFR >0.8 managed medically vs 73 pts with an FFR <0.8
managed surgically
Prospective application of predefined IVUS criteria
for revascularization of intermediate LM lesions:
Results at 2 years from the LITRO study
354 patients
MLA ≥6.0mm2
(n=186)
MLA <6.0mm2
(n=168)
7 revascularized
No LMCA revascularization
(n=179, 96%)
LMCA revascularization
(n=152, 90%)
16 not revascularized
56% PCI of other vessels55% CABG
45% PCI (+ other vessels in 62%
De La Torre Hernandez et al. J Am Coll Cardiol 2011;58:351-8
Survival free of cardiac
death, MI and any
revascularization
P=0.22
Defer (n=179)
Revascularization (n=152)
Survival free of cardiac
death
P=0.20
Defer
Revascularization
Clinical outcome of pts with vs without revascularization
In the group of 16 patients with
MLA <6mm2 who were treated
medically, cardiac death-free
survival to 2 years was 86%
(97.7% in the deferred group;
p=0.04), and survival free of
cardiac death, MI, and
revascularization was 62.5%
(87.3% in the deferred group;
p=0.02).
Clinical outcome of pts without revascularization according to the MLA
g
mas
nn
0 100 200 300 400 500 600 700 800 900
100
90
80
70
60
50
40
30
20
10
0
Time
Surv
ival p
roba
bility
(%)
De La Torre Hernandez et al. J Am Coll Cardiol 2011;58:351-8
Defer (medical therapy) with MLA ≥6mm2 (n=179)
Defer (medical therapy) with MLA <6mm2 (n=16)
Survival free of cardiac death
P=0.02
“Small” LM = Diffuse LMCA disease
• Murray’s Law
LMCAr3 = LADr3 + LCXr3
• Fractal Geometry
LMCAD = 0.678 (LADD + LCXD)
QCA DS (%)
Fractal QCA DS (%)
0
20
70
0
20
70
Matreff et al. Eurointervention 2010;5:709-15
Kang et al. Circulation Cardiovasc Interv. 2011;4:562-9
Criteria for stent underexpansion at the distal
LMCA bifurcation (n=403)
• MACE-free survival was
lower in pts with
underexpansion vs those
without underexpansion
(89.4% vs 98.1%)
• TLR-free survival was lower
in pts with underexpansion
vs no underexpansion
(90.9% vs 98.5%).
• Although acute
malapposition was observed
in 28 pts, malapposition was
not related to MACE at
follow-up.
Kang et al. Circulation Cardiovasc Interv. 2011;4:562-9
Two-Stent Techniques (n=114) One-stent Cross-over (n=289)
Impact of underexpansion on ISR in patients treated
with either two stents or a single stent cross-over
• 975 pts with unprotected LMCA stenosis
underwent elective stenting under IVUS (n=756)
or angiographic (n=219) guidance and were
followed for 3 years
• IVUS-guidance was significantly associated with
reduced death (HR=0.31 overall and HR=0.27 in
DES) as compared with angiography guidance
• However, the use of IVUS-guidance did not
reduce the risk of myocardial infarction or target
vessel revascularization.
Park et al. Circ Cardiovasc Intervent 2009;2:167-77
MAIN-COMPARE Registry
All-Cause Mortality After LMCA DES Implantation: Impact of IVUS Guidance
Cu
mu
lati
ve In
cid
en
ce (
%)
1.51.0Years after DES implantation
0.0 0.5 2.5 3.0
70
100
80
2.0
IVUS (n=595)
No IVUS (n=210)90
95.2%
85.6%
HR=0.43, p=0.019
Other independent predictors
were previous CHF, chronic renal
failure, COPD, and
EUROSCORE>6
(Park et al. Circ Cardiovasc Intervent 2009;2:167-77)
ADAPT-DES – IVUS vs No-IVUS Cohort -Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents
8,575 pts prospectively enrolled
No clinical or anatomic exclusion
criteria11 sites in US and Germany
Clinical FU at 30 days, 1 year
PCI with ≥1 non-investigational DES
Successful and uncomplicated
IVUS Use: 3349 pts No IVUS: 5234 pts
Witzenbichler, et al. TCT2012
MA
CE
(C
ard
iac
death
/MI/D
efi
nit
e-
Pro
bab
le S
T)
(%)
0
5
10
Time in Months
0 3 6 9 12
2538 2429 2399 2376 22563669 3466 3429 3387 3113
# at risk:IVUS +IVUS -
P= 0.021HR: 0.73 [95% CI: 0.55, 0.95]
3.1%
4.3%
IVUS Use
No IVUS Use
0
5
10
0 3 6 9 12
802 768 760 753 7021520 1424 1409 1399 1305
P= 0.022HR: 0.60 [95% CI: 0.39, 0.94]
3.3%
5.4%
Time in Months
Impact of Complexity of Procedure on
MACE
One vessel treatment≥2 vessel or left main
or bifurcation treated
Pre-intervention Post-intervention(1 stent cross-over)
FFR of “Jailed” LCX
R = -0.566
p = 0.004Fra
cti
on
al F
low
Res
erv
e
Percent Stenosis (%)
KNam et al. Korean Circ J 2011;41:304-7
%
43 LMCA bifurcation
lesions with a pre-PCI
LCX ostial DS<50%
were treated by single-
stent cross-over
MLA <3.7mm2
• Sensitivity 100%
• Specificity 71%
• PPV 16%
• NPV 100%
100-Specificity
Se
nsitiv
ity
0 20 40 60 80 100
100
80
60
40
20
0
AUC 0.80
95% CI 0.64–0.91
Plaque
Burden >56%• Sensitivity 100%
• Specificity 65%
• PPV 14%
• NPV 100%
100-Specificity
Se
nsitiv
ity
0 20 40 60 80 100
100
80
60
40
20
0
AUC 0.80
95% CI 0.63–0.92
Kang et al. Asan Medical Center, unpublished
0
2.0
4.0
6.0
8.0
10.0
12.0
pre post-stenting
ML
A w
ith
in L
CX
osti
um
(m
m2)
5.4mm24.0mm2
0
5.0
10.0
15.0
20.0
25.0
pre post-stenting
EE
M a
rea a
t th
e M
LA
sit
e (
mm
2)
11.8mm29.6mm2
0.5
1.0
1.5
2.0
2.5
3.0
pre post-stentingEE
M e
ccen
tric
ity in
dex a
t L
CX
cari
na
1.221.47
p=0.009 p=0.048
p<0.001
MLA within LCX ostium EEM area at MLA EEM eccentricity
78% showed a >10% reduction of MLA within LCX ostium after cross-over stenting
Kang et al. Circulation Cardiovasc Interv 2011;4:355-61
LMCA
LCX
LCX
Carina shift
• Use IVUS or FFR to assess LMCA severity
• FFR <0.80
• MLA <6mm2 in Western patients
• MLA <4.8mm2 in Asian patients
• Perform pre-intervention IVUS from both
the LAD and LCX to assess the extent of
the atherosclerosis
• Perform post-intervention IVUS to optimize
the implanted stent results
Conclusions