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