High-risk vulnerable plaques.

Kostis Raisakis

“G.Gennimatas” General Hospital of Athens

Overview:

1 Definition-Pathology

2Diagnostic Strategies

• Invasive• Non Invasive

3 Prognostic Value of Detection

4Treatment

• General• Focused

Overview:

1 Definition-Pathology

2Diagnostic Strategies

• Invasive• Non Invasive

3 Prognostic Value of Detection

4Treatment

• General• Focused

CV Death

NecrotomicExamination

Culprit Lesions

Histological Similarities with

Non-culprit Lesions

Vulnerable Plaques

Ex-vivo verification of

Modalities

New Modalities• Morphological• Molecular• Biochemical

• Ex-vivo verification• In-vivo comparison

• Prognostic Value• Algorithms

• Treatment Efficiency

1 Vulnerable PlaqueClinical Definition

Any thrombosis-prone plaque or plaque at a risk of rapid progression, with potential of becoming a culprit lesion and triggering an ACS, independent of its specific morphology

Naghavi et al, Circulation 2003

1

Virmani R, et al. Arterioscler Thromb Vasc Biol 2000

Vulnerable Plaque DefinitionPathological Substrate of Thrombosis

1 Vulnerable Plaque DefinitionThin-cap Fibroatheroma (TCFA)

Virmani R, et al. JACC 2006

Increased Plaque sizePositive remodeling

Increased Necrotic core~34% of plaque area~3.8 mm2 & ~9 mm long

Fibrous capReduced Thickness (<65 μm)Increased Macrophage Density, ~26% of capReduced Smooth Muscle Cells

Increased AngiogenesisNew MicrovesselsIntraplaque hemorrhage

Perivascular inflammation

Reduced Calcification & Spotty Calcification

1

Virmani R, et al. Arterioscler Thromb Vasc Biol 2000

Vulnerable Plaque DefinitionChallenges to the VP concept

Multiple Vulnerable plaques co-exist in the coronaries

How many of them did rupture?

All ruptures all fatal?

The vast majority of so called Vulnerable plaques do not exhibit clinical instability and seldom provokes ACS

All fatal events are caused by plaque rupture?

1 From Vulnerable Plaque to Vulnerable Patient

Toutouzas et al, EHJ 2015

Overview:

1 Definition-Pathology

2Diagnostic Strategies

• Invasive• Non Invasive

3 Prognostic Value of Detection

4Treatment

• General• Focused

Invasive ImagingAvailable Techniques for VP assessment

2a

Invasive Imaging/IVUSGrey Scale

Stenosis Severity Plaque Burden Positive Remodeling Calcification

2a

Tissue components of the plaque are correlated to specific colors

Invasive Imaging/IVUSVirtual Histology

2a

Intima thickness

thin-cap fibroatheroma

thick-cap fibroatheroma)

Fibro-calcified Plaque

Invasive Imaging/IVUSPlaque Characterization with IVUS-VH

2a

Invasive Imaging/OCTPlaque Characteristics

2a

High resolution Cap thickness Lipid core Macrophages Microvessels Spotty Calcification

Invasive Imaging/OCTPlaque Characterization with μOCT

2a

Liu L et al, Nat Med. 2011

Invasive Imaging/NIRSChemical Characterization of the Arterial Wall

2a

Madder et al, JACC Cardiovasc Interv. 2013Garg et al, Eurointervention 2013

Invasive Imaging/NIRSChemical Characterization of the Arterial Wall

2a

Toutouzas et al, JACC 2007

Novel Intravascular Imaging2a

Bourantas et al, EHJ. 2016

Hybrid Intravascular ImagingIVUS-OCT

2a

Bourantas et al, EHJ. 2016

Li et al, J Biomed Opt 2013

2b Non Invasive Imaging/MDCT

positive remodeling NCP plaque (areas of 30 HU)

spotty calcification

Detection of Calcium/Calcium score

Spatial resolution (240-600μm) does not permit the direct visualization of thin fibrous cap

Dimensions of the large necrotic core reach the detection threshold of CTA

Napkin-Ring Sign

2b Non Invasive Imaging/CTAPlaque Characterization

Motoyama et al, JACC 2007

2b Non Invasive Imaging/MDCTPlaque Characterization

Motoyama et al, JACC 2007

positive remodeling NCP plaque (areas of 30 HU)

spotty calcification

Stable Angina Pectoris

ACS

2b Non Invasive Imaging/CTANapkin-Ring Sign

Maurovich-Horvat et al, JACC Cardiov. Imag. 2010

plaque core with low CT attenuation surrounded by a rim-like area of higher CT attenuation as napkin ring like

large central lipid core surrounded by fibrous plaque tissue. deep micro-calcifications intramural thrombus neovascularization,

2b Non Invasive Imaging/MDCTPlaque Characterization/ Semi-automated software tool.

Ferencik et al, J Cardiovasc Comput Tomogr. 2015

positive remodeling NCP plaque (areas of 30 HU)

spotty calcification

2b Non Invasive Imaging/PET-CTfluorodeoxyglucose F18 (18F- FDG)

Naghavi et al, Circulation 2003

2b Non Invasive Imaging/PET-CT18F- FDG versus ⁸F-sodium fluoride(1⁸F-NaF)

Joshi et al, Lancet 2014

Overview:

1 Definition-Pathology

2Diagnostic Strategies

• Invasive• Non Invasive

3 Prognostic Value of Detection

4Treatment

• General• Focused

5 Future Perspectives

Stone et al. N Engl J Med. 2011

Prognostic Value of Imaging VP IVUS-VH/PROSPECT Study

3

Stone P et al. Circulation 2012

Prognostic Value of Imaging VP IVUS-ESS/ PREDICTION Study

3

Prognostic Value of Imaging VPATHEROREMO-NIRS Study

3

Oemrawsingh et al, JACC 2014

LCBI=Lipid Core Burden Index

3 Prognostic Value of Imaging VP CTA-Napkin ring sign

Otsuka et al. JACC Caridiovasc Imaging 2013

PR=Positive RemodelingLAP=Low Attenuation Plaque

Motoyama et al. JACC 2015

Prognostic Value of Imaging VP CTA

3

HRP=High Risk Plaque (positive remodeling and low attenuationplaques)

SS=Significant stenosis

Prognostic Value of Imaging VP PET/CT 18F- FDG

3

TBR=Target to Background Ratio

3 Prognostic Value of Imaging VP PET/18F-NaF

Overview:

1 Definition-Pathology

2Diagnostic Strategies

• Invasive• Non Invasive

3 Prognostic Value of Detection

4Treatment

• General• Focused

Medical Treatment for VP/StatinsPlaque regression4a

Tsujita et al. J Am Coll Cardiol. 2015

Medical Treatment for VP/StatinsAtheroma Calcification promotion

Puri et al. J Am Coll Cardiol. 2015

4a

PAV=percent atheroma volume

Medical Treatment for VP/StatinsNIRS/Plaque lipid depletion

Zhao et al. JACC Cardiovasc Imaging. 2011

4a

LRNC=Lipid-Rich Necrotic Core

Medical Treatment for VP/StatinsPET/CT, Vessel Inflammation

Tawakol et al. J Am Coll Cardiol. 2013

4a

TBR=Target to Background Ratio

Medical Treatment/StatinsMetanalysis for major events

Baigent et al. Lancet. 2010

4a

Medical Treatment for VP/OlmesartanPlaque burden regression/IVUS

Hirohata et al. J Am Coll Cardiol. 2010

4a

Medical Treatment for VP/EvolocumabGLAGOV study/IVUS

Puri et al. Am. Heart J. 2016

4a

Medical Treatment for VPPhase III Trials

De Caterina et al. Thromb Haemost 2016

4a

Invasive Sealing of VP4b

Invasive Sealing of VP4b

Summary

Accurate detection of VP is a “battle” and not “war” winning.

Novel imaging techniques provided new morphological information regarding VP.

Available Imaging is unable to completely assess plaque’s pathology and function.

Prognostic implications of the presence of VPs is questionable.

More accurate multi-modality techniques needed for stratification and identification of patients at risk for future events.

Novel treatment targeting both the vulnerable plaque and vulnerable patient needed

Thank you for your attention