high-risk vulnerable plaques.static.livemedia.gr/kebe/documents/al18587_us41...naghavi et al,...
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High-risk vulnerable plaques.
Kostis Raisakis
“G.Gennimatas” General Hospital of Athens
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Overview:
1 Definition-Pathology
2Diagnostic Strategies
• Invasive• Non Invasive
3 Prognostic Value of Detection
4Treatment
• General• Focused
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Overview:
1 Definition-Pathology
2Diagnostic Strategies
• Invasive• Non Invasive
3 Prognostic Value of Detection
4Treatment
• General• Focused
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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
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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
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1
Virmani R, et al. Arterioscler Thromb Vasc Biol 2000
Vulnerable Plaque DefinitionPathological Substrate of Thrombosis
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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
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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?
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1 From Vulnerable Plaque to Vulnerable Patient
Toutouzas et al, EHJ 2015
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Overview:
1 Definition-Pathology
2Diagnostic Strategies
• Invasive• Non Invasive
3 Prognostic Value of Detection
4Treatment
• General• Focused
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Invasive ImagingAvailable Techniques for VP assessment
2a
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Invasive Imaging/IVUSGrey Scale
Stenosis Severity Plaque Burden Positive Remodeling Calcification
2a
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Tissue components of the plaque are correlated to specific colors
Invasive Imaging/IVUSVirtual Histology
2a
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Intima thickness
thin-cap fibroatheroma
thick-cap fibroatheroma)
Fibro-calcified Plaque
Invasive Imaging/IVUSPlaque Characterization with IVUS-VH
2a
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Invasive Imaging/OCTPlaque Characteristics
2a
High resolution Cap thickness Lipid core Macrophages Microvessels Spotty Calcification
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Invasive Imaging/OCTPlaque Characterization with μOCT
2a
Liu L et al, Nat Med. 2011
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Invasive Imaging/NIRSChemical Characterization of the Arterial Wall
2a
Madder et al, JACC Cardiovasc Interv. 2013Garg et al, Eurointervention 2013
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Invasive Imaging/NIRSChemical Characterization of the Arterial Wall
2a
Toutouzas et al, JACC 2007
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Novel Intravascular Imaging2a
Bourantas et al, EHJ. 2016
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Hybrid Intravascular ImagingIVUS-OCT
2a
Bourantas et al, EHJ. 2016
Li et al, J Biomed Opt 2013
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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
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2b Non Invasive Imaging/CTAPlaque Characterization
Motoyama et al, JACC 2007
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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
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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,
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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
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2b Non Invasive Imaging/PET-CTfluorodeoxyglucose F18 (18F- FDG)
Naghavi et al, Circulation 2003
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2b Non Invasive Imaging/PET-CT18F- FDG versus ⁸F-sodium fluoride(1⁸F-NaF)
Joshi et al, Lancet 2014
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Overview:
1 Definition-Pathology
2Diagnostic Strategies
• Invasive• Non Invasive
3 Prognostic Value of Detection
4Treatment
• General• Focused
5 Future Perspectives
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Stone et al. N Engl J Med. 2011
Prognostic Value of Imaging VP IVUS-VH/PROSPECT Study
3
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Stone P et al. Circulation 2012
Prognostic Value of Imaging VP IVUS-ESS/ PREDICTION Study
3
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Prognostic Value of Imaging VPATHEROREMO-NIRS Study
3
Oemrawsingh et al, JACC 2014
LCBI=Lipid Core Burden Index
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3 Prognostic Value of Imaging VP CTA-Napkin ring sign
Otsuka et al. JACC Caridiovasc Imaging 2013
PR=Positive RemodelingLAP=Low Attenuation Plaque
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Motoyama et al. JACC 2015
Prognostic Value of Imaging VP CTA
3
HRP=High Risk Plaque (positive remodeling and low attenuationplaques)
SS=Significant stenosis
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Prognostic Value of Imaging VP PET/CT 18F- FDG
3
TBR=Target to Background Ratio
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3 Prognostic Value of Imaging VP PET/18F-NaF
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Overview:
1 Definition-Pathology
2Diagnostic Strategies
• Invasive• Non Invasive
3 Prognostic Value of Detection
4Treatment
• General• Focused
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Medical Treatment for VP/StatinsPlaque regression4a
Tsujita et al. J Am Coll Cardiol. 2015
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Medical Treatment for VP/StatinsAtheroma Calcification promotion
Puri et al. J Am Coll Cardiol. 2015
4a
PAV=percent atheroma volume
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Medical Treatment for VP/StatinsNIRS/Plaque lipid depletion
Zhao et al. JACC Cardiovasc Imaging. 2011
4a
LRNC=Lipid-Rich Necrotic Core
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Medical Treatment for VP/StatinsPET/CT, Vessel Inflammation
Tawakol et al. J Am Coll Cardiol. 2013
4a
TBR=Target to Background Ratio
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Medical Treatment/StatinsMetanalysis for major events
Baigent et al. Lancet. 2010
4a
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Medical Treatment for VP/OlmesartanPlaque burden regression/IVUS
Hirohata et al. J Am Coll Cardiol. 2010
4a
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Medical Treatment for VP/EvolocumabGLAGOV study/IVUS
Puri et al. Am. Heart J. 2016
4a
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Medical Treatment for VPPhase III Trials
De Caterina et al. Thromb Haemost 2016
4a
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Invasive Sealing of VP4b
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Invasive Sealing of VP4b
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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
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Thank you for your attention