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![Page 1: Imaging Coronarico Invasivo nella Prevenzione · PDF fileImaging Coronarico Invasivo nella Prevenzione Cardiovascolare. ... Grant all’ospedale: Abbott, Medtronic, Edwards, Shockwave](https://reader034.vdocuments.site/reader034/viewer/2022042611/5aaa3b8b7f8b9a9a188ded5b/html5/thumbnails/1.jpg)
Carlo Di Mario Professore Ordinario di Cardiologia
AOU Careggi, Firenze
Imaging Coronarico Invasivo nella Prevenzione Cardiovascolare
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DISCLOSURE INFORMATION
• Carlo Di Mario
negli ultimi due anni ho avuto i seguenti rapporti anche di finanziamento con soggetti portatori di interessi commerciali in campo sanitario:
Relatore: Philips-Volcano, Abbott, Astra-Zeneca
Grant all’ospedale: Abbott, Medtronic, Edwards, Shockwave
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1988-2017: 30 Years working with IVUS Erasmus University, Rotterdam, NL
Intracoronary Imaging
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Histopathologic Determinants of Plaque Vulnerability
Narula J et al. Nat Clin Pract Cardiovasc Med 2008
1
2
3
4 5
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My First OCT Images @RBH in 2004
1. 0.019” MicroOptic imaging
core (light source (wavelength
1310nm) and measures the
backscatter of light)
2. OTW occlusion balloon
catheter ( 2.7 Fr, balloon
inflated to 5 mm with low
pressure –0.3-0.5 Atm-) with
infusion of Ringer lactate max
0.5 – 1.0 ml/sec
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Incidental findings, 73 yo man, 9 months post stenting, with 2 weeks crescendo angina
OCT
Barlis, .., Di Mario: JACC Imaging
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IVUS OCT
MLD 4.1mm; MLA 11.6mm2 MLD 3.8mm; MLA 11.1 mm2
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38
1. ThCFA
*OM
5.3 mm2
Lesion prox
Baseline PLCX
QCA: RVD 2.82 mm, DS 28.6%, length 6.8 mm
IVUS: MLA 5.3 mm2
VH: ThCFA
700 pts with ACS UA (with ECGΔ) or NSTEMI or STEMI >24 hrs undergoing PCI of 1 or 2 major coronary arteries at
40 sites in the U.S. and Europe
PROSPECT 2011
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PROSPECT: MACE M
AC
E (%
)
Time in Years 0 1 2 3
All Culprit lesion (CL) related
Non culprit lesion (NCL) related Indeterminate
0
5
10
15
20
25
Number at risk
20.4%
12.9%
11.6%
2.7%
13.2%
7.9%
6.4%
0.9%
18.1%
11.4%
9.4%
1.9%
ALL 697 557 506 480
CL related 697 590 543 518
NCL related 697 595 553 521
Indeterminate 697 634 604 583
Stone GW et al. NEJM 2011;364:226-35
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PROSPECT: Correlates of Non Culprit Lesion Related Events at 3 Years F-Up
Lesion HR 3.8 (2.2, 6.6) 5.0 (2.9, 8.7) 7.9 (4.6, 13.8) 6.4 (3.4, 12.2) 6.7 (3.4, 13.0) 10.8 (5.5, 21.0) 10.8 (4.3, 27.2)
P value <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 Prevalence* 51.2% 49.1% 30.7% 17.4% 15.4% 11.0% 4.6%
*Likelihood of one or more such lesions being present per patient. PB = plaque burden at the MLA
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PROSPECT Case Example
MLA 4.0 mm2; plaque burden 72%; TCFA
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PROSPECT: NCL events arising from
stenoses with PB ≥70%
Prevalence* 10.1% 15.6% 5.6%
*Likelihood of one or more such lesions being present per patient. PB = plaque burden at the MLA
HR (95%CI) = 10.83 (5.55, 21.10)
P<0.0001
HR (95%CI) = 5.17 (2.59, 10.32)
P<0.0001
HR (95%CI) = 1.25 (0.17, 9.01)
P=0.83
Thin-cap fibroatheroma
Thick-cap fibroatheroma
Fibrocalcific Fibrotic
Pathologic intimal thickening
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VIVA 2011
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ATHEROREMO-IVUS 2014
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Plaque with >40%CSA St and focal necrotic rich core >10% CSA in contact with lumen
From Rodrigues-Granillo, Serruys et al JACC 2005
Virtual Histology
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Multiple components Variable scattering properties
Complex mixture spectra
÷
Low scatter
Medium scatter
High scatter
ms
l l l
ms
ms
Chemometric Algorithms
Algorithms extract the relevant portions of the mixture signal and create a probability map of lipid core plaque
NIRS Principle of Operation
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Adapted from Bourantas, et al. JACC 2013;16(13):1369
Combined IVUS and NIRS Catheter
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NIRS-IVUS with Histology
• Left • High plaque burden, calcium
shadowing and signal dropout on IVUS, but no lipid core plaque by NIRS
• Histology confirms calcified fibrous plaque
• Center • High plaque burden, calcium
shadowing and signal dropout on IVUS, and substantial lipid core plaque by NIRS
• Histology confirms large lipid core plaque
• Right • No plaque burden on IVUS and no
lipid core plaque by NIRS • Histology confirms normal vessel
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Initial Angio
3
25
16
44 12
33
50
46
*
*
*
*
*
*
*
*
20
TIMI 3 Flow NIRS Initial Angio TIMI 3 Flow NIRS
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STEMI culprit vs. non-culprit segments
STEMI culprit lesions:
maxLCBI4mm = 612 (438-817)
Non-STEMI lesions:
maxLCBI4mm = 78 (0-234)
MaxLCBI4mm >400 was present
at the STEMI culprit site in
63 of the 78 cases
MaxLCBI4mm >400 was present
at the non-culprit site in
22 of the 304 segments
Mann-Whitney U test
Median ± interquartile
range
Culprit Non-culprit0
100
200
300
400
500
600
700
800
900
1000
ma
xL
CB
I
p = < 0.0001
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In the cohort of 70 post PCI patients, only 4 had maxLCBI4mm >600 in non-stented area.
Stent placed in STEMI culprit
New culprit at vulnerable plaque site
Unstable Angina at 7 months
Intravascular Imaging in Secondary Prevention
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Hypercholesterolemic rabbit aorta TCFAs
Adapted from Moreno PR. Cardiol Clin 2010;28:1-30
Stent
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Neointima New Fibrous
Cap Thickness
Old Fibrous Cap Thickness
Lipid Core Strut
Adapted from Moreno PR. Cardiol Clin 2010;28:1-30
Hypercholesterolemic rabbit aorta TCFAs
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Everolimus Strut Beta-Estradiol Strut
Metallic & Polymer Strut De Novo TCFA
De Novo Lsns and Stents Deployed on TCFAs Adapted from Moreno PR.
Cardiol Clin 2010;28:1-30
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Everolimus Induced Autophagy of Macrophages
Verheye S et al. JACC 2007;49:706-15
EES and polymer only coated metallic stents implanted in atherosclerotic arteries of cholesterol-fed rabbits
EES resulted in marked
reduction of macrophage content, with
preservation of SMC content
Str
ut
cir
cu
mfe
ren
ce
su
rro
un
de
d b
y
ma
cro
ph
ag
es
of
SM
C (
%)
*** 0
20
40
60 Polymer control
Everolimus
MI SMC
RA
M-1
1 p
os
itiv
e a
rea
s
in p
laq
ue
(1
03 µ
m3)
*
0
20
40
100
Polymer
control
Evero- limus
60
80
Non- stented
RAM-11 stain; brown = macrophages
Polymer-coated stent Everolimus-eluting stent
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Bioresorbable Vascular Scaffolds (BRS)
Igaki-Tamai PLLA
Magnesium
(eluting paclitaxel) Biotronik Biosolve
PLLA (w/PDLLA
coat eluting
everolimus)
Abbott ABSORB
Reva ReSolve Iodinated tyrosine-
derivative (eluting
sirolimus)
Elixir DESolve PPLLA (eluting
novolimus)
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A B C D
A B C D
A B
C D
Lipid Rich Plaque Eccentric Plaque in a 39 Yrs Old Pt
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A B C
D
A
B
D C
D C
A
B
After 3.5 x 23 mm Everolimus Eluting Bioabsorbable Stent Expanded to 4.0 at 24 Atm
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PROSPECT II Study
PROSPECT ABSORB RCT
900 pts with ACS after successful PCI
3 vessel IVUS + NIRS (blinded)
≥1 IVUS lesion with ≥70% plaque burden present?
Routine angio/3V IVUS-NIRS FU at 2 years
Yes (N=300)
No (n=600)
ABSORB BVS + GDMT (N~150)
GDMT (N=150)
R 1:1
Clinical FU for MACE for ≥3 years
Co-Pis Dr. Gregg Stone Dr. David Erlinge
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The Lipid Rich Plaque (LRP) Study Dr. Ron Waksman, PI
PI, Japan, Dr. Takeshi Akasaka Co-PI, Japan, Dr. Yasunori Ueda
PI, Europe, Dr. Carlo Di Mario
9,000 PCI patients with ACS or SA will undergo NIRS-IVUS imaging of 2 or more vessels
3,000 with Max 4 mm LCBI >250 for 100% FU
6,000 with Max 4 mm LCBI ≤ 250 for 50% FU
2 year MACE from a new lesion at patient and coronary segment level
1400 patients enrolled; F-up expected to be completed end 2017
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European Heart Journal (2016) 37, 1883–1890
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Lifestyle Changes
Intravascular Imaging in Primary Prevention
Di Mario C. , European Heart Journal (2016) 37, 1883–1890
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What About Primary Prevention? From Primary to Secondary via CT
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9 months 82 NSTE ACS Total Atheroma V/ FCT by OCT IVUS
Total Atheroma V/ FCT by OCT IVUS
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AUTHOR / JOURNAL YEAR AIM No. PTS INTERVENTION Follow-up AT CHANGES OBSERVED
Takarada et al.
Atherosclerosis 2009
to determine whether
lipidlowering
therapy with statins could
increase the fibrous-cap
thickness of coronary
plaques
40 patients with AMI Statin use
RETROSPECTIVE 9 months
Although the
fibrous-cap thickness was
significantly increased in
both the statin treatment
group (151±110 to
280±120_m, p < 0.01) and
the control group (153±116
to 179±124_m, p < 0.01),
the degree of increase was
significantly greater in the
statin treatment
group than in the control
group (188±64% vs.
117±39%, p < 0.01).
Takarada et al.
JACC Cardiovasc
Interventions.
2010
to determine the
relationship between the
morphological changes of
nonculprit lipid-rich
plaques
82 patients with
NSTEACS - 9 months
FCT increased significantly
(95± 32 µm to 112 ± 45
µm,p = 0.05).
Statin use was an
independent predictor FCT
increase.
Uemura et al.
European Heart Journal 2012
to clarify the
morphological
characteristics of NSCPs in
patients with
CAD
53 patients (69
plaques) - 6-9 months
Compared with NSCPs
without progression, those
with progression showed a
significantly higher incidence
of intimal laceration,
microchannel, lipid pools ,
TCFA, macrophage images,
and intraluminal thrombi .
Hattori et al.
JACC Cardiovasc Imaging. 2012
to comprehensively assess
the impact of pitavastatin
on plaque characteristics
using a combination of
OCT, grayscale and IB-IVUS
42 patients with SAP 4 mg pitavastatin (26
patients) 9 months
A significant increase in FCT
(140 ± 42 μm, 189 ± 46
μm; p = 0.001) in statin arm.
Such changes were not
observed in the diet-only
group (140 ± 35 μm, 142 ±
36 μm; p = NS).
OCT Studies dealing with progression/changes unstable plaques over time
A significant increase in FCT (140 ± 42 μm, 189 ± 46 μm; p = 0.001) in statin arm. Such changes were not observed in the diet-only group (140 ± 35 μm, 142 ± 36 μm; p = NS
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2628 screened patients 1276 enrolled patients 970 randomized patients
evolocumab 420 mg administered monthly via subcutaneous injection for 76 weeks
JAMA 2016, (Epub ahead of print)
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Nicholls et al. JAMA 2016, (Epub ahead of print)
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Is It Reasonable to Apply Conventional Prevention Measures if CV Risk is 30% at 1 Year?
Fight to achieve lowest possible cholesterol, best diabetic control, true normalisation body weight, appropriate 24 hour BP reduction
Have low threshold to apply “unconventional” prevention measures: strongest maximal doses statins +/- ezitimibe, PCSK9 inhibitors, apheresis, modern antidiabetics +/- bariatric surgery
If bleeding risk low and previous history ACS/IC images showing vulnerable plaque, long term (>1 year) double antiplatelet therapy
Enrol them into a strict follow-up program to monitor results
Have low threshold to repeat non-invasive/invasive tests to monitor progression
Stent if lesion is functionally critical (irrespective of symptoms)
Stent irrespective of presence of flow reduction if ongoing trials show advantage