ANGIOPLASTY SUMMIT –TCTAP 2010

Imaging Workshop

OCT Findings: Lesson from Stable vs Unstable Plaques

Giulio Guagliumi MDOspedali Riuniti di Bergamo, Italy

DISCLOSURE OF FINANCIAL INTERESTS

ConsultantBoston ScientificVolcano

Grant/ Research SupportMedtronic Boston ScientificLightLab Imaging Abbott VascularLabcoat

Giulio GuagliumiOspedali Riuniti di Bergamo, Italy

Calcified Artery with/without Surface Lipid Pool

LP

Ca++

IVUSOFDI

G. Guagliumi and M. Costa Editorial Comment JACC Interv 2009 May18; 2: 467G. Guagliumi and M. Costa Editorial Comment JACC Interv 2009 May18; 2: 467

From a Foggy Sight to a Clear VisionFrom a Foggy Sight to a Clear Vision

ACS: Focus on mid-distal LAD

V. Sirbu Ospedali Riuniti di Bergamo

CSA=6.17mm² CSA=5.10mm² CSA=8.70mm²

CSA stenosis=31%

LAD LMFocus on proximal LAD

TCFA in Proximal LAD

Lipid plaque

Fibrous cap

30µm

100µm

Kubo et al. Expert Rev Med Dev. 2008;5:691-7

TCFA was defined as a plaque with fibrous cap <65µm thick. The high resolution of OCT has an ability to identify thin-fibrous cap clearly even if it is less than 100µm.

Thin-cap fibroatheroma (TCFA)

0

20

40

60

80

plaque rupture0

40

80

120

160

cap thickness0

0.5

1

1.5

2

2.5

MLA 0

10

20

30

40

ulceration/no cap rupture

% µm mm² %

Clinical Presentation and Plaque Morphology in Unstable Angina

M. Mizukoshi et al. i2 ACC. 2010; JACC Poster 1152-257

Class I Class II Class III

p<0.001 p<0.001 p=0.003 p<0.001

0

20

40

60

80

100

Plaque rupture

0

40

80

120

160

200

Cap Thickness

% µm

Multivessel Desease: SAP vs AMIInfarct Related Artery

Kubo T et al. Am J Cardiol 2010:105:318-322

SAP AMI

p<0.001 p=0.003 p<0.001

0

20

40

60

80

100

Thrombus

%

0

20

40

60

80

100

TCFA0

40

80

120

160

200

Cap Thickness

µm

Multivessel Desease: SAP vs AMINon Infarct Related Artery

Kubo T et al. Am J Cardiol 2010:105:318-322

SAP AMI

% p=0.030 p=0.002

①

②

③

④⑤

⑥

⑦

⑧ ⑨ ⑩ ⑪

⑫

⑬

①②

③

⑥⑦⑧⑨

⑩

⑪

⑬ ⑫

④ ⑤

The culprit lesion was in LCX (#11). TCFA (⑥), plaque rupture (⑦, ⑧) and intracoronary thrombus (⑦, ⑧) were observed by OCT. Although the plaques in LAD (⑫, ⑬) were not unstable, TCFA (①-⑤) and plaque rupture (③, ④, ⑤, ⑩, ⑪) were detected by OCT in the non-culprit lesions of RCA and LCX .

Kitabata, Kubo et al. Heart. 2008;94:544

Multiple plaque rupture in AMI: 3-vessel OCT examination

ACS Multilink ™3.0/25 mm 12 yrs after implant

G. Guagliumi, V. Sirbu Ospedali Riuniti di Bergamo

Ospedali Riuniti di Bergamo

LAD distally to the thrombotic stent site in VLST of BMS

Ospedali Riuniti di Bergamo

TCFA rupture

Ospedali Riuniti di Bergamo

TCFA rupture

32 µm

% necrotic-core: 22%Angle of the total NCCL 100.3º

Cap thickness; 40µmCap thickness; 40µm

NonNon--thinthin--cap IVUScap IVUS--derived TCFA n=33derived TCFA n=33

% necrotic-core: 15%Angle of the total NCCL 35.8º

Cap thickness; 90µmCap thickness; 90µm

T. Sawada, et al. EHJ 2008; 29(9):1136-1146

Use of VH-IVUS vs OCT for detecting in-vivo TCFA

Definite TCFA n= 28Definite TCFA n= 28

Non-TCFA VH +, OCT -

(n=33)

Non-TCFA VH +, OCT -

(n=33)

Definite-TCFAVH +, OCT +

(n=28)

Definite-TCFAVH +, OCT +

(n=28)

65.3 (39.3, 91.4)65.3 (39.3, 91.4)• Plaque volume (mm3/cm)• Plaque volume (mm3/cm)

1.10 (1.06, 1.13)1.10 (1.06, 1.13)• Remodelling index• Remodelling index

Gray-scale IVUSGray-scale IVUS

VHVH

• % Necrotic-core• % Necrotic-core

• Total NCCL angle (degree)• Total NCCL angle (degree)

T. Sawada, et al. EHJ 2008; 29(9):1136-1146T. Sawada, et al. EHJ 2008; 29(9):1136-1146

96.3 (75.6, 117.0)96.3 (75.6, 117.0)

1.21 (1.17, 1.25)1.21 (1.17, 1.25)

0.0010.001

0.00050.0005

18.6 (15.7, 21.4)18.6 (15.7, 21.4)

54.6 (35.6, 73.5)54.6 (35.6, 73.5)

20.0 (17.0, 22.9)20.0 (17.0, 22.9)

89.4 (63.6, 112.4)89.4 (63.6, 112.4)

NSNS

0.00030.0003

Combined use of IVUS-VH and OCT for detection of TCFACombined use of IVUS-VH and OCT for detection of TCFA

P P

G. Guagliumi, V. Sirbu Ospedali Riuniti di Bergamo

in-vivo Association between Positive Remodeling and TFCAIVUS and OCT imaging in 54 lesions from 48 pts

O. Raffael Eur Heart J 2008; 29:1721

0

20

40

60

80

100

Positive Absent Negative

Remodeling

p < 0.001

% of TCFA within each group

80 %

38.5 %

5.6 %

Cavity

Thrombus

Rupture Site

Cavity

Thrombus

NCNC

Cavity

IVUSOFDI

NCNC

Courtesy R. Virmani MD

FindingFinding OCT(n=30)OCT(n=30)

AS(n=30)AS(n=30) pp

Fibrous cap disruptionFibrous cap disruption

Fibrous cap erosionFibrous cap erosion

ThrombusThrombus

73% *†73% *†

100% †100% †

47%47%

3%3%

100% ‡100% ‡

0.0210.021

IVUS(n=30)IVUS(n=30)

40%40%

23% *†23% *† 0%0%

33%33%

0.0030.003

< 0.001< 0.001

OCT identifies plaque rupture, cap erosion and TCFA..and ThrombusOCT vs AS vs IVUS: 30 AMI pts

Kubo et al. J Am Coll Card 2007; 50: 933

* OCT vs AS, p<0.05. †OCT vs IVUS, p<0.01. ‡ AS vs IVUS, p<0.01.

OCT Findings of Culprit LesionsOCT Findings of Culprit Lesions

7070

STEMIn=40

STEMIn=40

NSTE ACSn=49

NSTE ACSn=49

P valueP value

9090

7878

4747

7171

4949

0.0330.033

0.0360.036

0.0080.008

55±2055±20 109±55109±55 0.00010.0001

7878 2727

00 3232

RedRedWhiteWhiteNoneNone

Thrombus %Thrombus %

Fibrous Cap Thickness µmFibrous Cap Thickness µm

TFCA %TFCA %

Lipid Rich Plaque %Lipid Rich Plaque %(>= 2 Quadrants)(>= 2 Quadrants)

Plaque Rupture %Plaque Rupture %

0.00010.0001

2222 4141

M. Riga i2ACC 2010, JACC A190 : 2501-503M. Riga i2ACC 2010, JACC A190 : 2501-503

OCT and IVUS Findings After PCI in UAP and SAP PatientsOCT and IVUS Findings After PCI in UAP and SAP Patients

T. Kubo et al J Am Coll Cardiovasc Imaging, July 2008:475-84T. Kubo et al J Am Coll Cardiovasc Imaging, July 2008:475-84

UAPUAP

SAPSAP

Inadequate *Stent Apposition

Inadequate *Stent Apposition

Tissue* Protrusion

Tissue* Protrusion

Intracoronary* Thrombus

Intracoronary* Thrombus

IVUS IVUS

(%)(%)

Inadequate Stent Apposition

Inadequate Stent Apposition

Tissue Protrusion

Tissue Protrusion

Intracoronary Thrombus

Intracoronary Thrombus

OCTOCT(%)(%)

P< 0.001p=0.001OCT vs IVUS*

� HORIZONS AMI: 2 Separated Lesions TAXUS 2.75 20 mm + 3.0 20 mm

Ospedali Riuniti di Bergamo

Index Procedure 13 month FU

HORIZONS OCT 13 mos FU

G. Guagliumi MD, Ospedali Riuniti di Bergamo

TAXUS 2.75 x 20 mm culprit lesion

TAXUS 3.0 20 mm non culprit

PSST

. 538

1 A

pril

2009

Pag

e 27

of 1

9

Difference in Difference in DES Incomplete Strut Apposition (ISA)DES Incomplete Strut Apposition (ISA)Stable /UA Stable /UA vsvs STEMI STEMI

STEMI: N=16

Stable/Unstable Angina : N=27

% Lesion with at least one ISA

% Frames with at least one ISA

% of Incompletely apposed struts

(%)p=0.01

N. Gonzalo et al JACC Int 2009; 2 (5): 445-452

Median follow-up time 9 months (range 7 to 72)DES: Cypher, Taxus, Xience, Biolimus

G. Guagliumi : HORIZONS Trial 3604 AMI randomized

B1

Thrombus Naturally or Pharmacologically Remodels OvertimeDelayed Healing? Late Incomplete Apposition?

STEMI

Postimplant

6 mos FU

G. Guagliumi, V. Sirbu Ospedali Riuniti di Bergamo

OCTAMI Trial : Index RCA Endeavor 3.0/24 mm

6 mos FU OCT

G. Guagliumi et al TCT Featured Clinical Research, JACC Intv 2010 May, in press

G. Guagliumi et al OCTAMI Featured Research TCT, JACC Intv 2010, May in pressG. Guagliumi et al OCTAMI Featured Research TCT, JACC Intv 2010, May in press

Coverage distribution in different cross-sections along the Stent 6-month FU

Coverage distribution in different cross-sections along the Stent 6-month FU

Proximal

Perc

enta

ge o

f Cov

ered

Stru

ts

DistalMid

ZESBMS(%)

HORIZONS OCT: 13 Months118 Consecutive STEMI pts enrolled in HORIZONS, 155 Taxus™ vs 45 BMS

Independent Core Labs Blind to the stent assignmentOCT Core Lab: Case Western Reserve Univeristy, Cleveland, OH

p=0.0003%

p<0.0001

G. Guagliumi et al, LBT Abstracts Circulation 2008;118:2309-17, submittedG. Guagliumi et al, LBT Abstracts Circulation 2008;118:2309-17, submitted

7,748 cross-sections- 44, 121struts

PSST

. 538

1 A

pril

2009

Pag

e 33

of 1

9

% Lesion with at least one uncovered

strut

% Frames with at least one uncovered strut

% Uncovered struts

(%)p=0.04

Median follow-up time 9 months (range 7 to 72)

N. Gonzalo et al JACC Int 2009; 2 (5): 445-452

Difference in Uncovered Strut Frequency Difference in Uncovered Strut Frequency -- DES DES

STEMI: N=16

Stable/Unstable Angina : N=27

0

5

10

15

20

25

30

35

-0.7 -0.5 -0.3 -0.1 0.1 0.3 0.5 0.7 0.9 1.1 1.3 1.5

Perc

ent o

f Stru

ts (%

)

Strut-Lumen Distance

%

mm

Consistent Strut Level Analysis among the OCT studies with PESHORIZONS OCT (AMI), ODESSA (Long Lesions with stent in overlap), OCTDESI (on label)

Trial Taxus Stentsn

Strutsn

FUmos

ODESSA Liberté 44 11,908 6Horizons OCT Express 115 34,142 13OCTDESI Liberté 19 34,474* 6

*based on every frame analysis

80,524

Backscattered power curves for calcific, fibrous and lipid tissues

Quantitative Analysis

0 100 200 300 400 500 600

100

101

depth (mm)

rela

tive

pow

er P

(z)/P

0(z)

calciumfiberlipid

Plaque type Backscattering coefficient

Attenuation coefficient

Calcification 4.9 ± 1.5 5.7 ± 1.4Fiber 19.2 ± 5.2 6.6 ± 0.7Lipid 29.7 ± 6.4 14.9 ± 2.5

Xu C, Schmitt J et al J Biomed Optics 2008 june ; 13: 034003

OFDI Instent restenosis

Macrophages

Courtesy R. Virmani MD

A. Tanaka , G. Tearney, B. Bouma J Biomed Optics Jan/Feb 2010

Plaque Characterisation

Stents

• Today, the in vivo assessment of entire segments of coronary arteries is possible due to significant improvements in imaging acquisition methods (FD-OCT).

• OCT lesion findings are related to clinical presentation (SAP ≠ ACS , STEMI ≠ non STEMI) and different in culprit compared with not culprit vessel.

• Simultaneous assessment of culprit and not culprit lesions can track atherosclerotic changes overtime (D cap tichkness, D number of TFCA,...) evaluating progression and regression and the effects of treatment.

• Challenging informations like macrophage density need to be further validated

• Incomplete struts apposition, plaque protrusion and thrombus formation after stenting are more frequently observed in UAP vs SAP.

• Data from randomized OCT based studies do not entirely support > uncovered struts in STEMI vs SAP/UAP when treated with PES

• The major expected advances in OCT for lesion assessment are at 3 different levels: cellular (texture parameters), plaque (tissue characterization spectroscopy) and vessel (3D volumetric rendering of the pathology)

Conclusions

OCT in Late and Very Late Stent Thrombosis

Case TIMEto LST DES type Indication at index Overlap DES

Length, mmAntiplatelet

therapy

1 485 SES ACS YES 28 Aspirine2 1438 SES ACS YES 33 Aspirine3 1836 SES ACS NO 18 Aspirine4 200 PES ACS YES 32 DAT5 365 PES SA YES 44 None6 1224 SES ACS NO 33 Aspirine7 172 EVES ACS NO 18 DAT8 275 PES ACS NO 24 DAT9 508 PES ACS YES 48 Aspirine10 508 PES ACS YES 48 Aspirine11 1103 SES SA YES 33 None12 590 PES ACS YES 100 Aspirine13 1174 PES ACS YES 36 Aspirine14 1093 PES ACS NO 24 Aspirine15 1078 PES ACS YES 48 Aspirine16 404 PES ACS NO 16 Aspirine17 569 ZES ACS YES 48 Aspirine18 640 PES ACS NO 24 Aspirine

Mean 579 days, (424-1100) 36±19 mm88%

V. Sibu ESC 2008, Young Investigator Awarded Session Thrombosis , ESC 2008

Baseline

15 mos

Prox end Distal end

Artery Wall

Lipid

Calcium

Macrophages

Stent

Guide Wire

Thrombus

Prox end Distal end

Courtesy G. Tearney MGH and B. Bouma MIT Boston