Validation and application of Validation and application of

IVUSIVUS--MLA in LMCA diseaseMLA in LMCA diseaseJose Mª de la Torre Hernandez, MD, PhD, FESC

Interventional Cardiology DptInterventional Cardiology DptCardiologia Valdecilla

Hospital Universitario Marques de ValdecillaSantander. SPAIN

Disclosure Statement of Financial Interest

Within the past 12 months, I or my spouse/partner have had a financial Within the past 12 months, I or my spouse/partner have had a financial p , y p pp , y p pinterest/arrangement or affiliation with the organizations listed below.interest/arrangement or affiliation with the organizations listed below.

Affiliation/Financial Relationship Company• Grant/Research Support • Abbott vascular, Cordynamic• Consulting Fees/Honoraria

• Major Stock Shareholder/Equity

• Abbott, Boston, Cordis, Medtronic, Biotronik, IHT, Lilly, Daychi Sankio, Astra Zeneca, Volcano, St Jude

• Royalty Income• Ownership/Founder• Intellectual Property Rightsp y g• Other Financial Benefit

Washington Heart Center Washington Heart Center ggexperienceexperience

122 pts with intermediate lesions and IVUS with no revascularizationand IVUS with no revascularization. 1 year follow up

Indep. predictors

IVUS MLD as predictor of events

Abizaid et al. J Am Coll Cardiol 1999;34:707-15

Proposed MLA cutProposed MLA cut--off values for LMoff values for LMKang et al. IVUS vs FFR <0.8 4.8 mm22011N= 55N= 55

J i l IVUS FFR 0 9 2Jasti et al. IVUS vs FFR < 0.75 5.9 mm22004N= 55

LITRODe la Torre et al. Physics of flow / Jasti et al. 6 mm2y2011N = 354

Fassa et al. Epidemiol. inferred 7.5 mm220052005N= 214

Clinical validation

Mayo Clinic ExperienceMayo Clinic Experience1994 to 2002: 214 intermediate LMCA lesions with IVUS

MLA cut-off value 7.5 mm2

214 intermediate LMCA lesions with IVUS

MLA cut off value 7.5 mm

Where does 7 5 mm2 comes from ?Where does 7.5 mm comes from ?

121 patients with: “angiographically normal” or “minimally diseased” LMCA

Mean MLA - 2 SDs = 7.5 mm2

Fassa et al. J Am Coll Cardiol 2005;45:204 –11

Mayo Clinic ExperienceMayo Clinic Experience1994 to 2002: 214 intermediate LMCA lesions with IVUS

Mayo Clinic ExperienceMayo Clinic Experience

Fassa et al. J Am Coll Cardiol 2005;45:204 –11

Mayo Clinic ExperienceMayo Clinic ExperienceMayo Clinic ExperienceMayo Clinic Experience

> 7.5 Revasc

< 7.5 Revasc

> 7.5 Deferred

< 7.5 Deferred

Fassa et al. J Am Coll Cardiol 2005;45:204 –11

IVUS IVUS –– FFR in intermediate lesionsFFR in intermediate lesionsi ill U i di ill U i dLouisville Univ. studyLouisville Univ. study

55 patients55 patients

IVUS - FFRIVUS - FFR

Correlation:

FFR 0.75

IVUS MLA5.9 mm2

Jasti et al. Circulation 2004;110:2831-6

Valdecilla Hospital ExperienceValdecilla Hospital ExperienceP ti li ti fP ti li ti f MLA 6MLA 6 22 tt ff lff lProspective application of Prospective application of MLA 6 mmMLA 6 mm22 as cutas cut--off value off value

MACE in a 40MACE in a 40±±17 months follow up17 months follow up79 ptsp25-50% LMCA stenosiswith IVUSwith IVUS

MLA < 6 mm2 REVASCMLA > 6 mm2 DEFERMLA > 6 mm2 DEFER

Only 2 cases with LM revascularization in 8 years follow up97 6% free of LM revascularization at 5 years

De la Torre Hernandez et al. Rev Esp Cardiol. 2007;60:811-6

97.6% free of LM revascularization at 5 years

MLA 6 2LMCA

MLA 4 2

MLA = 6 mm2Proximal LADMLA = 4 mm2

Proximal LCxJasti et al CirculationMLA = 4 mm2

Jasti et al. Circulation 2004;110:2831-6

LMCAr3 = LADr3 + LCXr3

Non-LM intermediate lesions: MLA t ff 4 2MLA cut-off 4 mm2

Abizaid, et al. Circulation 1999;100:256, 256—61

Abizaid et al. Am J Card 1998;82:423.8

Correlation IVUS Correlation IVUS –– FFR in nonFFR in non--LMLML i MLA f FFR MLA f FFRLesions MLA for FFR

< 0.75MLA for FFR < 0.8

Takagi 1999 51 3 mm2

B i i 53 4 2Briguori 2001 53 4 mm2

Ben-Dor 2011 92 2 8 mm2 3 2 mm2Ben-Dor 2011 92 2.8 mm2 3.2 mm2

Koo 2011 267 2.8 mm2Koo 2011 267 2.8 mm

Kang 2011 236 2.4 mm2

Gonzalo 2012 61 2.4 mm2

F1RST 2013 367 3 mm2

VERDICT 2013 312 2.9 mm2

Waksman R, et al. FIRST: Fractional Flow Reserve and Intravascular Ultrasound Relationship Study.J Am Coll Cardiol. 2013 Mar 5;61(9):917-23.

Clinical outcomes after IVUS and FFR assessment of intermediate coronary lesions. Propensity score matching of large cohorts from y p y g g

two institutions with differential approach.400 pts with FFR assessment vs. 400 pts with IVUS assessment

MLA < 4 mm2 in vessels >3 mmMLA < 3.5 mm2 in vessels 2.5-3 mm

Overall

Deferred

De la Torre Hernandez et al. Eurointervention(In press)

THE FRACTAL NATUREOF VASCULAR TREESArterial bifurcations have a 3DArterial bifurcations have a 3Dblood-distribution function

Q1D1 = D major daughter vessel

QoDo = D mother vessel

Q2D2 = D minor daughter vessel

Law of flow (mass) conservation Qo = Q1+Q2

Murray´s law Do3 = D13 + D23Murray s law Do = D1 + D2HK 7/3 model Do7/3 = D17/3 + D27/3

Linear law (epicardial coronary artery) Do = 0.678*(D1+D2)*( p y y) ( )

* Finet G et al. Eurointervention 2007;3:10-17

Finet G et al.Eurointervention 2007;3:10-17

Huo Y et al.EuroIntervention 2012;7:1310-1316

Threshold for MLA in prox. LAD - LCx

LAD / LCx MLA 3 3.5 4

Murray`s law

LM MLA 5 5.5 6

Linear law

LM MLA 5 8 6 4 7 3LM MLA 5.8 6.4 7.3

MLA 6 2LMCA

MLA 3 2

MLA = 6 mm2Proximal LADMLA = 3 mm2

Proximal LCx (incl. dominant)

MLA = 3 mm2

( )Jasti et al. Circulation 2004;110:2831-6

Linear law (epicardial coronary artery)D 0 678*(D1 D2)Do = 0.678*(D1+D2)

Finet G et al EurointerventionFinet G et al. Eurointervention 2007;3:10-17

THE CLINICAL VALIDATION for 6 mm 2

22 centers (inclusion in 2007)

De la Torre Hernandez, et al. J Am Coll Cardiol 2011; 58:351-8

RESULTSRESULTSPopulation includedPopulation included

354 pts

2 2MLA ≥ 6 mm2 MLA < 6 mm2

186 pts 168 pts

7 revascularized 16 no revascularized

No Revascularización LM Revascularización LM179 pts (96%) 152 pts (90%)179 pts (96%) 152 pts (90%)

56% PCI in other lesions 55% CABG45% PCI of LMCA45% PCI of LMCA (+ other lesions in 62%)

Clinical outcome of pts with deferredrevascularization (MLA > 6 mm2)

100

90

80

70

y (%

) Survival free of cardiac death, MI and LMCA revascularizacion

60

50

l pro

babi

lity

at 2 years:

94 2± 1 8%40

30

20

Surv

iva 94.2 ± 1.8%

20

10

00 150 300 450 600 750

0

Time

Compared clinical outcome in pts p pwith and without LMCA revascularization

1 0 0

9 0

Defer

9 0

8 0

7 0

Revasc

7 0

6 0Cardiac death

5 0

4 0P=0.5

3 0

2 0

0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0

1 0

00 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0

T im e

Compared clinical outcome in pts p pwith and without LMCA revascularization

1 0 0

Defer9 0

8 0

Defer

Revasc7 0

6 0

5 0

Cardiac death, MI and any revascularizacion

5 0

4 0

3 0

P=0.3

3 0

2 0

1 0

0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0

1 0

0

T im e

Compared clinical outcome in deferred pts p pwith MLA > 6mm2 (n=179) and < 6 mm2 (n=16)

1 0 0

9 0 6 D f9 0

8 0

7 0

> 6 Defer

7 0

6 0

5 0

< 6 Defer

C di d th MI d5 0

4 0

3 0

Cardiac death, MI and any revascularizacion

3 0

2 0P=0.02

0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0

1 0

00 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0

T im e

Patients with deferred LM revascularization

MLA 5 - 6 mm2 6 - 7.5 mm2

Nº pts 16 53

Events 5 (31.2%) 3 (5.6%)

FFRFFR

VSVS.

IVUS

Stenosis MLD

LITRO

MLA > 6 MLA<6 MLA > 6 MLA<6

MLA > 6 MLA < 6

Outcomes in both studies

1 0 0

9 0

(179) DEF > 6(138) DEF > 0.8

8 0

7 0

6 0(152) REV < 6

(75) REV < 0.86 0

5 0

4 0MACEMACE

3 0

2 0

1 0

0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0

1 0

0

T im eT im e

2 yrs 2 yrsFFR studyHamilos et al.

IVUS studyDe la Torre Hernandez et al.

55 ptspLM stenosis 30 – 80%

4.8 mm 2

Kang SJ et al. J Am Coll Cardiol Intv 2011; 4: 1168-1174

No follow up providedNo follow up provided

71% f l i ith FFR 0 75 0 871% of lesions with FFR 0.75 - 0.8 29% of lesions with FFR > 0.8

Revascularized

Deferring LMCA revascularization:safety concerns

Sensitivity 100%

safety concerns

2 2

Sensitivity 100%

4.8 mm2 6 mm2

Kang et al. Jasti et al.

Differences between studiesDifferences between studies

Kang et al. Jasti et al. LITRO study

MLA, mm2 4.9 7.6 7.2

PB % 69 59 59PB, % 69 59 59

EEM area, mm2 17.8 18.7 18.8

Method FFRIV adenosine

FFRIC

adenosine

Clinicalvalidation

adenosine42 - 56 g

Cut-off MLA 4 8 5 9 6Cut-off MLA 4.8 5.9 6

Euro PCR 2012

Intravascular ultrasound comparison of left main coronary artery disease between white and asian patients.Rusinova RP, Mintz GS, Choi SY, et al. Am J Cardiol. 2013 Apr 1;111(7):979-84.Cardiovascular Research Foundation, New York, New York; Columbia University Medical Center, New York, New Yor

99 Asian patients (Japan and South Korea) 99 matched control United States white patients

ith t bl li i l t ti d >30% LMCA t iwith a stable clinical presentation and >30% LMCA stenosis

At the minimum lumen site and over the entire LMCA length Asian patients had a:

Smaller lumen area (5 2 ± 1 8 vs 6 2 ± 14 mm2; p <0 0001)Smaller lumen area (5.2 ± 1.8 vs 6.2 ± 14 mm2; p <0.0001)

Larger vessel area (20.0 ± 4.9 vs 18.4 ± 4.4 mm2; p <0.0001)

Larger plaque burden (72 ± 10 vs 64 ± 12%: p <0.0001)

FFR is more appropriate in assessing i t di t l iintermediate lesions

Why IVUS in ambiguous LM ?Why IVUS in ambiguous LM ?y gy g• There is probably more agreement between IVUS and

FFR in assessing LM lesion significance than in assessing non-LM lesions

Li it d i bilit i LM l th– Limited variability in LM length– Limited variability in supplied myocardium

Large LM size– Large LM size

• Main limitations for FFRMain limitations for FFR– Gray zone 0.75-0.8 or even could be 0.75-0.85 for LM (?)– No characterization of LM disease (specially in bifurcations)– Not fully reliable in presence of severe LAD / LCx disease

• IVUS provides anatomic information• IVUS provides anatomic information – IVUS may be used to guide LM PCI

FFR – MLA in LM vs non-LM lesions

Severe lesions in LAD or LCx:FFR measurement not reliable

Differential involvement of LAD / LCx ostiumFFR measurement not reliable

for LM assessmentof LAD / LCx ostiumDifferent FFR readings

TheThe ““doubledouble valuevalue” of IVUS” of IVUSTheThe doubledouble valuevalue of IVUS of IVUS

IVUSCABG (40 45%)*

LMCACABG (40-45%)*

Significant40 45%

intermediatelesion

40 – 45%

FFR PCI (55-60%)*

IVUS

*National registry RENACIMIENTO (Baz et al ACC 2010)National registry RENACIMIENTO (Baz et al. ACC 2010)1479 patients with severe LM disease

Patients with MLA > 6mm2 and deferred revascularization in LITRO study

Revascularization of LM in follow up

No Yes*n= 171 n=8

MLD 2.9 ± 0.6 2.5 ± 0.7MLA 9.3 ± 3 8.4 ± 2.1

MLA:MLA:6-7 20% 25%7-8 17% 25%8-9 18.5% 12.5%> 9 43.8% 37.5%

* 4 (50%) showed lesion progression at the time of revascularization

Average MLA in pts incurring events g gafter deferred revascularization

LITRO study Okabe et al. Abizaid et al.

8.4 ± 2 7.2 ± 2.2 6.8 ± 4.4

Ok b t l J I C di l 2008 20 635 9Okabe et al. J Invas Cardiol 2008;20:635-9Abizaid et al. J Am Coll Cardiol 1999;34:707-15De la Torre, et al. J Am Coll Cardiol 2011; 58:351-8

9 th9 months

9 monthsMLA 10 4 2 PB 59% MLA 5 7 mm2 PB 75%9 monthsMLA 10.4 mm2 PB 59% MLA 5.7 mm2 PB 75%

Plaque burden in LM diseasePlaque burden in LM disease

• PB > 67% predictor of FFR < 0.75 in LM (in Jasti et al )(in Jasti et al.)

• PB > 72% predictor of FFR < 0 8 in LM• PB > 72% predictor of FFR < 0.8 in LM (in Kang et al.)

• PB was the only predictor of events in deferred LM l i ti ft 5LM revascularization after 5 years(in Okabe et al.)

Jasti et al. Circulation 2004;110:2831-6. Kang SJ et al. J Am Coll Cardiol Intv 2011; 4: 1168-1174. Okabe et al. J Invas Cardiol 2008;20:635-9

MLA cut-off for LM

5 mm2 6 mm2 7 5 mm2

Small body size Diabetes insulin dep

5 mm 6 mm 7.5 mm

Small body size

Elderly

Diabetes insulin-dep.Big body sizeHigh physical activity

(low physical activity)

PB < 60%

(young, sports, job,..)

MV diseaseNo positive remodelling

Positive RemodellingPB > 70%TCFA

S t i i t tSymptoms, non-invasive tests, ...

¡¡ Treat the patient and not the numbers ¡¡

ConclusionsConclusions• IVUS is a safe method to accurately assess the severity

of ambiguous LM lesions.

• An “universal definite cutoff value” for the LM lumen does not exist.

• There is a narrow range for the LM MLA around 6 mm2gand modulation by other factors is required to make an individual case-based decision:

– Population and patient profileCli i l f– Clinical features

– Angiography: LM and overall coronary treeIVUS PB AS l h l d lli VH– IVUS: PB, AS, plaque morphology, remodelling, VH

– In selected cases, >>> FFR