Is OCT Ready for Is OCT Ready for ““Prime Prime TimeTime””??TimeTime ? ?

WhatWhat’’s known and what we need s known and what we need to know for clinical applicationto know for clinical application

Gary S. Mintz, MDGary S. Mintz, MDCardiovascular Research FoundationCardiovascular Research Foundation

N Y k NYN Y k NYNew York, NYNew York, NY

Pre-intervention Lesion Assessment• Plaque composition

• Calcium• Aneurysms

• True• Fibrous tissue• Lipid

• False• Spontaneous

• Thrombus• TCFA

dissection• Muscle bridge

• Fibrous cap thickness• Macrophages

• Erosions

• SVG disease• Transplant

l th• Erosions• Calcific nodules• Plaque rupture

vasculopathy• Lesion severity

LMCA• Plaque rupture • LMCA• Non-LMCA

OCT vs HistologyOCT vs HistologyFibrousFibrous LipidLipid--richrich CalcificCalcific MacrophagesMacrophagesFibrousFibrous LipidLipid--richrich CalcificCalcific

RawMacrophagesMacrophages

Logarithmic

CD68 Immuperoxidase

•• High reflectivityHigh reflectivity•• HomogenousHomogenous•• Finely texturedFinely textured

•• Low reflectivityLow reflectivity•• HomogenousHomogenous•• Diffuse marginsDiffuse margins

•• Low reflectivityLow reflectivity•• InhomogenousInhomogenous•• Sharp marginsSharp marginsyy Diffuse marginsDiffuse margins Sharp marginsSharp margins

SensitivitySensitivity SpecificitySpecificity PPVPPV NPVNPVFibrousFibrous .87.87 .97.97 .88.88 .96.96CalcificCalcific .95.95 1.01.0 1.01.0 .95.95LipidLipid .92.92 .94.94 .81.81 .97.97

Interobserver k = 0.88; Intraobserver k = 0.91Interobserver k = 0.88; Intraobserver k = 0.91Interobserver k 0.88; Intraobserver k 0.91Interobserver k 0.88; Intraobserver k 0.91

Yabushita et al. Circulation 2002;106:1640-5Tearney et al. Circulation 2003;107:113-9

WhiteWhite Light YellowLight Yellow YellowYellow Intense YellowIntense Yellow

Red Thrombus Red Thrombus

S iti it 95%S iti it 95%Sensitivity = 95%Sensitivity = 95%Specificity = 88%Specificity = 88%Positive predictive value = 86%Positive predictive value = 86%ppNegative predictive value =95%Negative predictive value =95%

White Thrombus White Thrombus

•• Red thrombusRed thrombus was identified as highwas identified as high--backscattering protrusions backscattering protrusions inside the lumen of the artery, with signalinside the lumen of the artery, with signal--free shadowing in thefree shadowing in theinside the lumen of the artery, with signalinside the lumen of the artery, with signal free shadowing in the free shadowing in the OCT image.OCT image.

•• White thrombusWhite thrombus was identified as lowwas identified as low--backscattering projections backscattering projections in the OCT imagein the OCT imagein the OCT image. in the OCT image.

(Kubo et al. Circulation 2006;114:II-645 )

In vivo comparison of OCT and angioscopy in assessing culprit lesions in 30 AMI patientsg p p

Plaque rupture

Incidence=73% Incidence=47% Incidence=40%

Plaque Erosion

Plaque erosionIncidence 73% Incidence 47% Incidence 40%

q

Incidence=23% Incidence=3% Incidence=0%

(Kubo et al. J Am Coll Cardiol 2007;50:933(Kubo et al. J Am Coll Cardiol 2007;50:933--9)9)

Difference of Culprit Lesion Morphologies Between ST-Segment Elevation Myocardial Infarction and Non–ST-

S El i A C S d

STEMI NSTE-ACS p

Segment Elevation Acute Coronary Syndrome

STEMI NSTE-ACS p# 40 49Plaque rupture 28 (70) 23 (47) 0.033Cavity area, mm2 2.52±1.36 1.67±1.37 0.034Aperture open against direction of coronary flow

46% 17% 0.036direction of coronary flow

Lipid-rich plaque 90% 71% 0.036Fibrous cap thickness, µm 55±20 109±55 <0.001p , µTCFA 78% 49% 0.008Thrombus 100% 65% <0.001Red thrombus 78% 27% <0.001White thrombus 22% 39% 0.114

Ino et al.. J Am Coll Cardiol Intv, 2011;4:76-82

Pre-intervention Lesion Assessment• Plaque composition

• Calcium• Aneurysms

• True• Fibrous tissue• Lipid

• False• Spontaneous

• Thrombus• TCFA

dissection• Muscle bridge

• Fibrous cap thickness• Macrophages

• Erosions

• SVG disease• Transplant

l th• Erosions• Calcific nodules• Plaque rupture

vasculopathy• Lesion severity

LMCA• Plaque rupture • LMCA• Non-LMCA

OCT-Guided Stent implantation• High risk plaques• Stent sizingg

• Diameter• Length

• Stent optimization – clinically important endpoints• Stent optimization – clinically important endpoints• MSA• Inflow/outflow disease• Complications – dissections, intramural hematomas,

perforations, etc Others• Others

• Malapposition• Prolapse• Thrombus

• Comparison with angiography guidance

Patients with NSTE ACS who underwent OCT and successfulunderwent OCT and successful emergent primary stenting were divided into two groups on the basis of post-stent TIMI flow: no-preflow group (n = 14) and reflow group (n = 69). Thin-cap fibroatheroma were more frequently observed in the no-reflow group than in the reflow group (50% vs. 16%, P = 0.005)Th f f th flThe frequency of the no-reflow phenomenon increased according to the size of the lipid arc in the culprit plaque. p p q

Tanaka et al. Eur Heart J 2009;30:1348-1355

OCT-Guided Stent implantation• High risk plaques• Stent sizingg

• Diameter• Length

• Stent optimization – clinically important endpoints• Stent optimization – clinically important endpoints• MSA• Inflow/outflow disease• Complications – dissections, intramural hematomas,

perforations, etc Others• Others

• Malapposition• Prolapse• Thrombus

• Comparison with angiography guidance

0 6.5mm 26.0mm

5 05 0 5.45.3

5.05.0

5.0

4.3

4.2

3.8

4.0

2 52.5

• Largest reference lumen (prox or dist)• Midwall

Increasingly • Midwall• Media-to-media (typically discounted)

aggressive

MetaMeta--analysis of IVUS guidance of analysis of IVUS guidance of BMS implantationBMS implantation

MACE

BMS implantationBMS implantation

TULIP

DIPOL

IVUS guidance was associated with significantly lower rate of •Angiographic restenosis (22 2% Gaster

RESIST

SIPS

•Angiographic restenosis (22.2% vs. 28.9%; OR 0.64, p=0.02)•Repeat revascularization (12.6% vs 18 4%; OR 0 66 p=0 004) SIPS

AVID

OPTICUS

vs. 18.4%; OR 0.66, p=0.004)•Overall MACE (19.1% vs. 23.1%; OR 0.69, p=0.03)b i ifi ff MI

.1 1 10

Combined (RE)Combined (FE)

but no significant effect on MI (p=0.51) or mortality (p=0.18).

Favors Non-IVUSFavors IVUS Odds Ratio

Predictors of DES Predictors of DES Thrombosis & RestenosisThrombosis & RestenosisThrombosis & RestenosisThrombosis & Restenosis

DES ThrombosisDES Thrombosis DES RestenosisDES RestenosisF jii t l J A C ll C di l 2005 45 995F jii t l J A C ll C di l 2005 45 995 8)8) S d t l J A C llS d t l J A C llSmall MSA or MLA or Small MSA or MLA or

underexpansionunderexpansion••Fujii et al. J Am Coll Cardiol 2005;45:995Fujii et al. J Am Coll Cardiol 2005;45:995--8)8)••Okabe et al., Am J Cardiol. 2007;100:615Okabe et al., Am J Cardiol. 2007;100:615--2020••Liu et al JACC Cardiovasc IntervLiu et al JACC Cardiovasc Interv

••Sonoda et al. J Am Coll Sonoda et al. J Am Coll Cardiol 2004;43:1959Cardiol 2004;43:1959--6363••Hong et al. Eur Heart J Hong et al. Eur Heart J 2006;27:13052006;27:1305--1010Liu et al. JACC Cardiovasc Interv. Liu et al. JACC Cardiovasc Interv.

2009;2:4282009;2:428--3434••Choi et al. Circ Cardiovasc Interv (in press)Choi et al. Circ Cardiovasc Interv (in press)

••Doi et al JACC Cardiovasc Doi et al JACC Cardiovasc Interv. Interv. 2009;2:12692009;2:1269--7575••Fujii et al. Circulation Fujii et al. Circulation 2004 109 10852004 109 1085 108810882004;109:10852004;109:1085--10881088••Kang et al. Circ Kang et al. Circ Cardiovasc Interv 2011;4:9Cardiovasc Interv 2011;4:9--1414••Choi et al. HORIZONS, Choi et al. HORIZONS, unpublishedunpublished

Edge problems Edge problems ••Fujii et al. J Am Coll Cardiol 2005;45:995Fujii et al. J Am Coll Cardiol 2005;45:995--8)8) ••Sakurai et al. Am J Cardiol Sakurai et al. Am J Cardiol 2005 96 12512005 96 1251 33

g pg p(geographic miss, (geographic miss, secondary lesions, secondary lesions, large plaque burden,large plaque burden,

••Okabe et al., Am J Cardiol. 2007;100:615Okabe et al., Am J Cardiol. 2007;100:615--2020••Liu et al. JACC Cardiovasc Interv. Liu et al. JACC Cardiovasc Interv. 2009;2:4282009;2:428--3434

2005;96:12512005;96:1251--33••Liu et al.Am J Cardiol Liu et al.Am J Cardiol 2009;103:5012009;103:501--66••Costa et al, Am J Cardiol,Costa et al, Am J Cardiol,large plaque burden, large plaque burden,

dissections, etc)dissections, etc)2009;2:4282009;2:428 3434••Choi et al. Circ Cardiovasc Interv (in press)Choi et al. Circ Cardiovasc Interv (in press)

Costa et al, Am J Cardiol, Costa et al, Am J Cardiol, 2008;101:17042008;101:1704--1111

1296 IVUS1296 IVUS--guided, DESguided, DES--treated lesions in 884 pts treated lesions in 884 pts vs 1312 propensityvs 1312 propensity--scorescore--matched, angiomatched, angio--guided, guided,

DESDES--treated lesions in 884 ptstreated lesions in 884 pts

IVUSIVUS--guideguide

dd

AngioAngio--guidedguided

pp

IVUS100(%)

30 day30 day

MACEMACE 2.8%2.8% 5.2%5.2% 0.010.01

Stent thrombosisStent thrombosis 0.5%0.5% 1.4%1.4% 0.0450.045

No-IVUSp=0.013

ee S

urvi

val

TLRTLR 0.7%0.7% 1.7%1.7% 0.0450.045

1 year1 year

MACEMACE 14.5%14.5% 16.2%16.2% 0.30.3

95

ombo

sis

Fre

MACEMACE 14.5%14.5% 16.2%16.2% 0.30.3

Definite stent thrombosisDefinite stent thrombosis 0.7%0.7% 2.0%2.0% 0.0140.014

Probable stent thrombosisProbable stent thrombosis 4.0%4.0% 5.8%5.8% 0.080.08

TLRTLR 5 1%5 1% 7 2%7 2% 0 060 06 0 126190S

tent

-thro

TLRTLR 5.1%5.1% 7.2%7.2% 0.060.06

Late definite stent Late definite stent thrombosisthrombosis

0.2%0.2% 0.7%0.7% 0.30.3Months of followMonths of follow--upup

0 1261

(Roy et al. Eur Heart J 2008;29:1851(Roy et al. Eur Heart J 2008;29:1851--7)7)

Stent Follow-up• Mechanisms of ISR or stent thrombosis

• Thrombus• Intimal hyperplasia• Composition of neointimal tissue• Underexpansion• Strut fracture• Neoatherosclerosis• Others

• Tissue coverage• Malapposition• Severity of ISR lesion• Predictors of subsequent eventsed cto s o subseque t e e ts

Lumen Area, Stent Area, Strut-Lumen Distance Strut-Vessel Wall Distance

Total strut thickness +

½ of the

Strut blooming

Strut

½blooming

Polymer

Malapposed distance

Protruding Protruding MalapposedEmbedded Protruding Covered

Protruding Uncovered

MalapposedEmbedded

Abnormal intraluminal tissueAbnormal intraluminal tissue

Fl ti flFl ti fl R l t d t NIHR l t d t NIH R l t d tR l t d tR l t d tR l t d tFloating flapFloating flap Related to NIHRelated to NIH Related to malapposed

struts

Related to malapposed

struts

Related to uncovered

struts

Related to uncovered

struts strutsstrutsstrutsstruts

BL: black box

F ll U St t St t AFollow-Up Stent Strut Appearance

Preserved box Open box Dissolved bright box

Dissolved black box

Sharp defined, bright reflection borders with preserved box shaped appearanceStrut body shows low reflection

Luminal and abluminal“long-axis” borders thickenedbright reflection;“short axis” borders not visible

Partially visible bright spot, contours poorly definedno box shaped appearance

Black spot, contours poorly defined, often confluentno box shaped appearance

OCT Analysis in HORIZONS and ODESSAStents analyzed every 0.3 mm - 7,748 cross-sections or 43,884 struts in 117 pts in HORIZONS and 6,968 cross-sections or 53.047 struts in 77 pts

in ODESSA

Guagliumi et al TCT2008 and AHA2008

Primary Endpoint in ODESSAProportion of uncovered and/or malapposed struts at the

Primary Endpoint in ODESSAProportion of uncovered and/or malapposed struts at theProportion of uncovered and/or malapposed struts at the

overlap point in BMS vs DES Proportion of uncovered and/or malapposed struts at the

overlap point in BMS vs DES

%

P=0.081

1 8±4 0 2.75.4±14.3

1.8±4.02.71.8

Guagliumi et al JACC Cardiovasc Interv. 2010;3:531-9.

Primary End-Point in HORIZONS-OCTProportion of uncovered and malapposed struts at 13 monthsProportion of uncovered and malapposed struts at 13 months

p=0.0003p=0.0003%

p<0.0001p<0.0001

Guagliumi et al Circulation. 2011;123:274-81

Cypher 2.5x28mm, 3.0x18mm, 3.0x13mm, and 3.5x8mm: VLST at 4 years

Ospedali Riuniti di Bergamo

In-stent Neoatherosclerosis after DES (n=50, median follow-up of 32 months)

• 52% lesions had at least one in-stent TCFA-like neointima• 58% had at least one in-stent neointimal rupture. • Fibrous cap thickness negatively correlated with follow-up time (r=-0 318Fibrous cap thickness negatively correlated with follow up time (r 0.318,

p=0.024). • 20 months post-implantation was the best cut-off to predict TCFA-like

neointima). DES ≥20 months post-implantation hadneointima). DES ≥20 months post implantation had Higher incidence of TCFA-like neointima (69% vs. 33%, p=0.012)Higher incidence of red thrombi (27% vs. 0%, p=0.007).

Kang et al. Circulation, in press

Late in-stent neoatherosclerosis in DES

Microvessel TCFA-like neointima Calcium Red thrombus

Neointimal rupture Mixed thrombus

White thrombus

Kang et al. Circulation, in press

Recent OCT studies from have shown the frequent in-stent thrombi at follow-up.

F/U (mos)

BMS SES PES EES ZES

Kim. JACC Cardiovasc Interv 2009;2:1240-7

3 1 (3.2%)

Murakami. Circ J 2009;73:1627-34

6 3 (15%) 10 (50%)34Davlouros. Int J Cardiol 2011, in press

6 16 (21.7%)

Yamamoto. Int J Cardiol 2010, in press

3-8 10 (33%)

Inoue. Heart 2010, in press 8 30 (0%)

Kim. Circ J. 2010;74:320-6 9 10 (33.3%) 5 (18.5%)

Choi. Int J Cardiovasc Imaging 2011, in press

9 24 (34.3%) 8 (5.0%)

Kim. Am Heart J 2010;159:278-83 3-66 (11) 27 (28%) 7 (11%)

Stent Follow-up• Mechanisms of ISR or stent thrombosis

• Thrombus• Intimal hyperplasia• Composition of neointimal tissue• Underexpansion• Strut fracture• Neoatherosclerosis• Others

• Tissue coverage• Malapposition• Severity of ISR lesion• Predictors of subsequent eventsed cto s o subseque t e e ts

For OCT to be ready for prime time, the major clinical needs of the interventional community – guidance of

t t i l t ti t b tstent implantation – must be met.

• Pre-interventione te e t oDevelop a paradigm for selecting stent length and diameter, a paradigm that does not rely on visualizing true vessel dimensions as a point of reference . . . or abandon pre-intervention imaging. . . a step backward. . . and only perform post-stent OCTy p p

• Post-intervention• Develop endpoints for optimal stent implantation

based on outcomes data. Some may be similar to IVUS, but others may be different. . .

• Follow up• Follow-up• Show that OCT findings have clinical relevance in

terms of predicting long term eventsterms of predicting long term events

• Develop practical and standardized analyses• Educate the interventional community to accurately

interpret the images and use the information correctlyTh i d ti th t t i t ti li t• The images are so seductive that most interventionalists believe that they intuitively understand the pathology when, in fact, they are often wrong.

• Elegant morphologic descriptors may be great for research purposes and for understanding clinical

h b t t h t l h OCT i tphenomena, but are not enough to launch OCT into “prime time” – ie., use in clinical applications.

• In the last 5 years there have been >150 peer reviewed• In the last 5 years there have been >150 peer-reviewed publications on OCT in coronary disease patients, but none have addressed its practical clinical application.p pp

• There is still a lot of work to be done.