OCT Findings: Lesson from Stable vs Unstable Plaques

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ANGIOPLASTY SUMMIT TCTAP 2010 Imaging Workshop OCT Findings: Lesson from Stable vs Unstable Plaques Giulio Guagliumi MD Ospedali Riuniti di Bergamo, Italy

DISCLOSURE OF FINANCIAL INTERESTS Consultant Boston Scientific Volcano Grant/ Research Support Medtronic Boston Scientific LightLab Imaging Abbott Vascular Labcoat Giulio Guagliumi Ospedali Riuniti di Bergamo, Italy

Calcified Artery with/without Surface Lipid Pool Ca ++ LP OFDI IVUS

From a Foggy Sight to a Clear Vision G. Guagliumi and M. Costa Editorial Comment JACC Interv 2009 May18; 2: 467

ACS: Focus on mid-distal LAD V. Sirbu Ospedali Riuniti di Bergamo

LAD Focus on proximal LAD LM CSA stenosis=31% CSA=6.17mm² CSA=5.10mm² CSA=8.70mm²

TCFA in Proximal LAD

Thin-cap fibroatheroma (TCFA) Fibrous cap Lipid plaque 30µm 100µm 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. Kubo et al. Expert Rev Med Dev. 2008;5:691-7

Clinical Presentation and Plaque Morphology in Unstable Angina 80 Class I Class II Class III % p<0.001 160 µm p<0.001 2.5 mm² p=0.003 40 % p<0.001 60 120 2 30 1.5 40 80 1 20 20 40 0.5 10 0 plaque rupture 0 cap thickness 0 MLA 0 ulceration/no cap rupture M. Mizukoshi et al. i2 ACC. 2010; JACC Poster 1152-257

Multivessel Desease: SAP vs AMI Infarct Related Artery SAP AMI 100 % 100 % 200 µm 80 p<0.001 p=0.003 160 p<0.001 80 60 60 120 40 40 80 20 20 40 0 Plaque rupture 0 Thrombus 0 Cap Thickness Kubo T et al. Am J Cardiol 2010:105:318-322

Multivessel Desease: SAP vs AMI Non Infarct Related Artery SAP AMI 100 % p=0.030 200 µm p=0.002 80 160 60 120 40 80 20 40 0 0 TCFA Cap Thickness Kubo T et al. Am J Cardiol 2010:105:318-322

Multiple plaque rupture in AMI: 3-vessel OCT examination 1 2 1 2 6 7 6 7 8 9 10 13 12 13 12 11 3 4 5 3 4 5 8 9 10 11 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

ACS Multilink 3.0/25 mm 12 yrs after implant G. Guagliumi, V. Sirbu 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 Ospedali Riuniti di Bergamo

Use of VH-IVUS vs OCT for detecting in-vivo TCFA Non-thin-cap IVUS-derived TCFA n=33 % necrotic-core: 15% Angle of the total NCCL 35.8º Cap thickness; 90µm Definite TCFA n= 28 % necrotic-core: 22% Cap thickness; 40µm Angle of the total NCCL 100.3º T. Sawada, et al. EHJ 2008; 29(9):1136-1146

Combined use of IVUS-VH and OCT for detection of TCFA Non-TCFA VH +, OCT - (n=33) Definite-TCFA VH +, OCT + (n=28) P Gray-scale IVUS Plaque volume (mm 3 /cm) 65.3 (39.3, 91.4) 96.3 (75.6, 117.0) 0.001 Remodelling index 1.10 (1.06, 1.13) 1.21 (1.17, 1.25) 0.0005 VH % Necrotic-core 18.6 (15.7, 21.4) 20.0 (17.0, 22.9) NS Total NCCL angle (degree) 54.6 (35.6, 73.5) 89.4 (63.6, 112.4) 0.0003 T. Sawada, et al. EHJ 2008; 29(9):1136-1146

G. Guagliumi, V. Sirbu Ospedali Riuniti di Bergamo

in-vivo Association between Positive Remodeling and TFCA IVUS and OCT imaging in 54 lesions from 48 pts % of TCFA within each group 100 p < 0.001 80 60 80 % 40 20 0 38.5 % 5.6 % Positive Absent Negative Remodeling O. Raffael Eur Heart J 2008; 29:1721

OFDI Rupture Site IVUS NC NC Cavity Cavity Cavity Thrombus Thrombus NC NC Courtesy R. Virmani MD

OCT identifies plaque rupture, cap erosion and TCFA..and Thrombus OCT vs AS vs IVUS: 30 AMI pts Finding OCT (n=30) AS (n=30) IVUS (n=30) p Fibrous cap disruption 73% * 47% 40% 0.021 Fibrous cap erosion 23% * 3% 0% 0.003 Thrombus 100% 100% 33% < 0.001 * OCT vs AS, p<0.05. OCT vs IVUS, p<0.01. AS vs IVUS, p<0.01. Kubo et al. J Am Coll Card 2007; 50: 933

OCT Findings of Culprit Lesions STEMI n=40 NSTE ACS n=49 P value Plaque Rupture % Lipid Rich Plaque % (>= 2 Quadrants) TFCA % Fibrous Cap Thickness µm Thrombus % Red White None 70 90 78 47 71 49 0.033 0.036 0.008 55±20 109±55 0.0001 78 27 22 41 0 32 0.0001 M. Riga i2acc 2010, JACC A190 : 2501-503

OCT and IVUS Findings After PCI in UAP and SAP Patients (%) UAP IVUS SAP (%) Inadequate * Stent Apposition p=0.001 OCT Tissue* Protrusion Intracoronary* Thrombus OCT vs IVUS* P< 0.001 Inadequate Stent Apposition Tissue Protrusion Intracoronary Thrombus T. Kubo et al J Am Coll Cardiovasc Imaging, July 2008:475-84

HORIZONS AMI: 2 Separated Lesions TAXUS 2.75 20 mm + 3.0 20 mm Index Procedure 13 month FU Ospedali Riuniti di Bergamo

HORIZONS OCT 13 mos FU TAXUS 2.75 x 20 mm culprit lesion TAXUS 3.0 20 mm non culprit G. Guagliumi MD, Ospedali Riuniti di Bergamo

Difference in DES Incomplete Strut Apposition (ISA) Stable /UA vs STEMI (%) p=0.01 Median follow-up time 9 months (range 7 to 72) DES: Cypher, Taxus, Xience, Biolimus STEMI: N=16 Stable/Unstable Angina : N=27 % Lesion with at least one ISA % Frames with at least one ISA N. Gonzalo et al JACC Int 2009; 2 (5): 445-452 % of Incompletely apposed struts PSST. 5381 April 2009 Page 27 of 19

Thrombus Naturally or Pharmacologically Remodels Overtime Delayed Healing? Late Incomplete Apposition? B1 G. Guagliumi : HORIZONS Trial 3604 AMI randomized

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

Coverage distribution in different cross-sections along the Stent 6-month FU (%) BMS ZES Percentage of Covered Struts Proximal Mid Distal G. Guagliumi et al OCTAMI Featured Research TCT, JACC Intv 2010, May in press

HORIZONS OCT: 13 Months 118 Consecutive STEMI pts enrolled in HORIZONS, 155 Taxus vs 45 BMS % p=0.0003 p<0.0001 Independent Core Labs Blind to the stent assignment OCT Core Lab: Case Western Reserve Univeristy, Cleveland, OH 7,748 cross-sections- 44, 121struts G. Guagliumi et al, LBT Abstracts Circulation 2008;118:2309-17, submitted

Difference in Uncovered Strut Frequency - DES (%) p=0.04 Median follow-up time 9 months (range 7 to 72) STEMI: N=16 Stable/Unstable Angina : N=27 % Lesion with at least one uncovered strut % Frames with at least one uncovered strut N. Gonzalo et al JACC Int 2009; 2 (5): 445-452 % Uncovered struts PSST. 5381 April 2009 Page 33 of 19

Consistent Strut Level Analysis among the OCT studies with PES HORIZONS OCT (AMI), ODESSA (Long Lesions with stent in overlap), OCTDESI (on label) 35 % Trial Taxus Stents n Struts n FU mos Percent of Struts (%) 30 25 20 15 10 ODESSA Liberté 44 11,908 6 Horizons OCT Express 115 34,142 13 OCTDESI Liberté 19 34,474 * 6 80,524 5 0-0.7-0.5-0.3-0.1 0.1 0.3 0.5 0.7 0.9 1.1 1.3 1.5 mm *based on every frame analysis Strut-Lumen Distance

Backscattered power curves for calcific, fibrous and lipid tissues Quantitative Analysis relative power P(z)/P 0 (z) 10 1 10 0 calcium fiber lipid 0 100 200 300 400 500 600 depth (mm) Plaque type Backscattering coefficient Attenuation coefficient Calcification 4.9 ± 1.5 5.7 ± 1.4 Fiber 19.2 ± 5.2 6.6 ± 0.7 Lipid 29.7 ± 6.4 14.9 ± 2.5 Xu C, Schmitt J et al J Biomed Optics 2008 june ; 13: 034003

A. Tanaka, G. Tearney, B. Bouma J Biomed Optics Jan/Feb 2010 OFDI Instent restenosis Macrophages Courtesy R. Virmani MD

Plaque Characterisation Stents

Conclusions 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)

Case TIME to LST OCT in Late and Very Late Stent Thrombosis DES type Indication at index Overlap DES Length, mm Antiplatelet therapy 1 485 SES ACS YES 28 Aspirine 2 1438 SES ACS YES 33 Aspirine 3 1836 SES ACS NO 18 Aspirine 4 200 PES ACS YES 32 DAT 5 365 PES SA YES 44 None 6 1224 SES ACS NO 33 Aspirine 7 172 EVES ACS NO 18 DAT 8 275 PES ACS NO 24 DAT 9 508 PES ACS YES 48 Aspirine 10 508 PES ACS YES 48 Aspirine 11 1103 SES SA YES 33 None 12 590 PES ACS YES 100 Aspirine 13 1174 PES ACS YES 36 Aspirine 14 1093 PES ACS NO 24 Aspirine 15 1078 PES ACS YES 48 Aspirine 16 404 PES ACS NO 16 Aspirine 17 569 ZES ACS YES 48 Aspirine 18 640 PES ACS NO 24 Aspirine Mean 579 days, (424-1100) 88% 36±19 mm V. Sibu ESC 2008, Young Investigator Awarded Session Thrombosis, ESC 2008

Artery Wall Lipid Calcium Macrophages Stent Guide Wire Thrombus Baseline Prox end Distal end 15 mos Prox end Courtesy G. Tearney MGH and B. Bouma MIT Boston Distal end