Novel insights into atherosclerosis: from pathology to ... · PIT w/o LP M PIT with M ... PCI for...
Transcript of Novel insights into atherosclerosis: from pathology to ... · PIT w/o LP M PIT with M ... PCI for...
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Dr. med. Philipp Nicol
Deutsches Herzzentrum München
MAC - Munich Vascular Conference 2017
Novel insights into atherosclerosis:
from pathology to invasive imaging
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Disclosure
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I do not have any potential conflict of interest✗
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Agenda
Insights into atherosclerosis and plaque vulnerability from
histopathology
Innovative imaging
- Overview of current techniques
- Preclinical and clinical application
Invasive imaging for atherosclerosis
- Overview of current techniques
- Detection of progressive CAD and vulnerable lesions
1
2
3
Summary4
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Agenda
Insights into atherosclerosis and plaque vulnerability from
histopathology
Innovative imaging
- Overview of current techniques
- Preclinical and clinical application
Invasive imaging for atherosclerosis
- Overview of current techniques
- Detection of progressive CAD and vulnerable lesions
1
2
3
Summary4
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Development of atherosclerotic lesions
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Early atherosclerosis can develop into with high risk lesions (“vulnerable
plaques”) rupture and vessel thrombosis
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Causes of coronary thrombosis
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Th
Nodular
Ca++
Calcified nodule (2-7%)Rupture (65-70%) Erosion (30-35%)
Th
Th
NC
Th
NC
Th Th
Underlying PIT Underlying FA
Virmani et al. ATVB 2000
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Causes of coronary thrombosis
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Th
Nodular
Ca++
Calcified nodule (2-7%)Rupture (65-70%) Erosion (30-35%)
Th
Th
NC
Th
NC
Th Th
Underlying PIT Underlying FA
Virmani et al. ATVB 2000
Causes of ACS
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Agenda
Insights into atherosclerosis and plaque vulnerability from
histopathology
Innovative imaging
- Overview of current techniques
- Preclinical and clinical application
Invasive imaging for atherosclerosis
- Overview of current techniques
- Detection of progressive CAD and vulnerable lesions
1
2
3
Summary4
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Overview
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OCT IVUS NIRS-IVUS
Mode Infraredlight Ultrasound Spectroscopy
Resolution 10-15μm 150 – 200μm 150 – 200μm
Depth 2-3mm 10mm 10mm
Radiation No No No
Contrast medium Yes No No
Detection Fibrotic cap,
makrophages,
Necrotic core,
calcification
Remodeling, plaque
burden, calcification
Lipidic plaque
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IVUS vs. OCT
75 mm, 100-150 µm axial resolution, low sampling rate, 150 sec
75 mm, 15 µm axial resolution, high frequency samples, 2 sec
IVUS
OCT
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OCT for detection of progressive
atherosclerotic lesions
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LPPIT w/o M
PIT with M
Early FA
Late FA
Early
NC
LP
Macrophages
IVUS OCT Histology
Late
NCFA=fibroatheroma; LP=lipid pool; NC=necrotic core; PIT=pathologic intimal thickening
Otsuka and Joner, Nat Rev Cardiol. 2014
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Detection of culprit lesions in ACS by OCT
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Calcified nodule
(9%)
Plaque rupture
(53%)
Plaque erosion
(38%)
Jia et al., JACC. 2013
Similar incidence in histology and OCT!
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OCT improves percutaneous
angioplasty…
CLI-OPCI
PCI with CAG only
vs.
PCI + OCT
(n=670; non-randomized)
1) Improved outcome (less MI and
cardiac deaths) in the +OCT-
group
2) OCT revealed periprocedural
complications
DESIGNResults
ILUMIEN III
PCI with CAG only
vs.
CAG+ IVUS
vs.
CAG + OCT
(n=450, randomized)
1) Enhanced stentexpansion adn
improved procedural success
with OCT
2) OCT revealed periprocedural
complications
DOCTORS:
PCI for NSTEMI with CAG
vs.
CAG + OCT
(n=240, raandomized)
1) Significantly improved
procedural success with OCT
(higher FFR post-PCI)
2) OCT revealed periprocedural
complications
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What do we know about vulnerable
lesions – PROSPECT trial
• 679 pts. with ACS underwent
CAG and VH-IVUS
• FU 3,4 years
• MACE: 20,4% (culprit: 12,9%,
non-culprit:11,6%)
• Non-culprit lesions responsible
for MACE were only mildly stenotic
on CAG but classified as TCFA
and plaque burden >70% with
VH_IVUS
14Stone et al. NEJM 2011
Intravascular imaging could be
superior to CAG in detecting plaque
vulnerability!
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Can OCT detect vulnerable plaques?
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Validation of OCT for TCFA
(n=685 plaques)
+TCFA
histology
-TCFA
histology
+TCFA
OCT
12 17
-TCFA
OCT
0 669
Sensitivity 12/(12+0) = 100%
Specifity 673/(17+673) = 98%
PPV 12/(12+17) = 41%
NPV 673/(673+0) = 100%
Fujii et al. JACC imaging 2015
OCT is able to detect vulnerable plaques (TCFA); false positive results are due to
foam cells, calcifications or thrombus obscuring the underlying pathologies!
Otsuka and Joner, Nat Rev Cardiol. 2014
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Agenda
Insights into atherosclerosis and plaque vulnerability from
histopathology
Innovative imaging
- Overview of current techniques
- Preclinical and clinical application
Invasive imaging for atherosclerosis
- Overview of current techniques
- Detection of progressive CAD and vulnerable lesions
1
2
3
Summary4
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Concept of molecular imaging
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• Novel and innovative imaging
approaches are needed to detect
vulnerable lesions unambigously
• Current imaging technologies provide
infomation regarding the structural
plaque composition but lack the
ability to visualize plaque biology
• Molecular imaging is able to detect
biologically relevant features of
plaque progression*, probably
enabling the visualization of
plaque vulnerability
• Fibrin
• Neovascularization
• Proteaseses (= cap thinning)
• Macrophages
• LDL
• Endothelial cells
• …
*
Lauschner, F. & Nahrendorf M., Circ. 2011
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Many technologies, many (dis-
)advantages…
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Bourantas C. et al.; EHJ 2016
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NIRF-IVUS
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• Combination of near-infrared
fluorescence and IVUS in a
dual imaging system
(4F/40MHz)
• The hybrid image is
reconstructed by combining the
structural ultrasound
information with precisely
co-registered NIR fluorescence
emission signals.
cNIRF
10 20 30 40 50 60 70 80
200
400
600
800
1000
1200
0. 05
0. 1
0. 15
0. 2
0. 25
0. 3
0
10 20 30 40 50 60 70 80
200
400
600
800
1000
1200
0.05
0.1
0.15
0.2
0.25
0.3
0.8uM
0
1.4uM
ICG,FITC
cNIRF-IVUScatheter
cNIRF-IVUScatheter
FM
AF
EB
ICG
CD31
NIRF-IVUS FM
(a)
(b) (c) (d)
(e)
Bozhko D., et al. EHJ Cardiovasc. Imaging 2016
Visualization of endothelial
disintegrity by injection of a
fluorescent tracer (indocyanine
green, ICG) in a swine iliac artery
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First clinical application -
autofluorescence
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• Necrotic cores show elevated
autofluorescence in the NIRF-
range (NIRAF)
• Imaging with NIRF-OCT
system in patients undergoing
PCI for stable CAD (n=12)
• NIRAF intensity was elevated
in plaques with a high-risk
morphological phenotype
(p < 0.05)
Plaque-related autofluoresence
could be used as an endogenous
imaging parameter for detection
of vulnerable lesions!
Ughi G., et al. JACC: Cardiovasc. Imaging 2016
66-year old diabetic patient with unstable angina and moderate to
severe stenosis of the LCX and moderate stenosis of the LAD
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Agenda
Insights into atherosclerosis and plaque vulnerability from
histopathology
Innovative imaging
- Overview of current techniques
- Preclinical and clinical application
Invasive imaging for atherosclerosis
- Overview of current techniques
- Detection of progressive CAD and vulnerable lesions
1
2
3
Summary4
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Summary
• Histopathology has showed us the progression of early
atherosclerotic lesions lesions into plaques with a high risk of rupture
and vessel occlusion (vulnerable plaques)
• Intravascular imaging with OCT is able to visualize all steps of
atherosclerotic development but is not able to reveal all vulnerable
plaques due to technical limitations
• Molecular imaging describes a whole range of applications used to
visualize processes involved in the plaque progression
• Various markers (externally and internally) can be used to to visualize
epitopes involved in these processes (e.g. NIRF)
• Clinical application is still limited but will hopefully increase in the
future
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Thank you for your attentention