Pedro R. Moreno, MD, FACC Associate Professor of Medicine Director nterventional Cardiology Research Mount Sinai Medical Center New York, New York Stents In Vulnerable Plaque: Pre-Clinical Results sclosure: Grant from Guidant Co. Advisor Prescent Tec
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Pedro R. Moreno, MD, FACCAssociate Professor of Medicine
DirectorInterventional Cardiology Research
Mount Sinai Medical CenterNew York, New York
Stents In Vulnerable Plaque:
Pre-Clinical Results
Disclosure: Grant from Guidant Co.Advisor Prescent Tec
Saka
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8-15
65
Coronary Thrombosis Before and After Stenting
30 day post Stenting 6 months post Stenting
Before PTCA After PTCA After Stenting
Vulnerable Plaque (TCFA)
Falk E, et al Circulation 1995;92:657-71
Atheromatous Core
Fibrous CapMacrophages
Dilemma: Hypothesis Versus a Real Clinical Problem
Can stents stabilize vulnerable plaques?What about Drug-Eluting Stents?
Plaque Area (mm2) Percent Lipid Area (%)Lipid Area (mm2) Fibrous Cap Thickness (µm)
Vessel wall Injury score
Score0
Score1
Score2
Score3
Schwartz RS, et al. J Am Coll Cardiol. 1992;19:267–274
NeointimaNew Fibrous
Cap Area
Old Fibrous Cap Area
Lipid Core Strut
Strut Quantitative Measurements
• De-novo: Seventy-six segments were analyzed to identify 33 de-novo TCFA lesions.
• Stents: 64 stents and 192 stented segments with a total of 1584 struts analyzed.
Metallic (n= 127)
Beta-Estradiol(n=46)
Everolimus(n=41)
Polymer (n=23)
237 struts deployed on TCFA plaques
Metallic and DES as a Potential Treatment to Stabilize Vulnerable Plaques
Lipid Core Area & Fibrous Cap Thickness
Vascular Healing Patterns
Stent-Induced Fibrous Cap Rupture
0
20
40
60
80
100
120
Lipid Area Old Fibrous CapArea
New Cap Area
0.0001 0.0001 0.0001
De-novo Vs. Metallic
0
20
40
60
80
100
120
Lipid Area Old Fibrous CapArea
New Cap Area
0.0001 0.004 0.0001
De-novo Vs. -Estradiol
0
20
40
60
80
100
120
Lipid Area Old Fibrous CapArea
New Cap Area
0.0001 0.001 0.0001
m2
De-novo Vs. Everolimus
De-Novo
-Estradiol
Metallic
Everolimus
Eche
verr
i D, P
urus
hoth
aman
KR
, M
oren
o PR
.
De-novo Vs. Metallic and DES
In comparison with de-novo TCFA, stented TCFA shows reduced lipid core area, reduced old fibrous cap thickness and increased new fibrous cap thickness areas.
Metallic and DES as a Potential Treatment to Stabilize Vulnerable Plaques
Lipid Core Area & Fibrous Cap Thickness
Vascular Healing Patterns
Stent-Induced Fibrous Cap Rupture
Score 0: No inflammation around strut. Score I: Scattered; cells <25% around strut. Score II: cells covering 25-50% around strut. Score III: Deposition 50-75% around strut. Score IV: Deposition 100% around strut.
Inflammation Score 0: No fibrin present around strut. Score I: Deposition in <25% around the strut. Score II: Deposition 25-50% around strut. Score III: Deposition 50-75% around strut. Score IV: Deposition 100% around strut.
Fibrin Deposition
Score 0: No red cells present around strut. Score I: Deposition in <25% around the strut. Score II: Deposition in 25-50% around strut. Score III: Deposition in 50-75% around strut. Score IV: Deposition in 100% around strut.
Hemorrhage Score 0: No EC present on the strut. Score I: Covered <25% on the strut by EC Score II: Covered 25-75% on the strut by EC Score III: Covered 100% around strut by EC Score IV: Strut covered by neointimal tissue.
• TCFA with stent-induced fibrous cap rupture were more frequently found than TCFA without stent-
induced fibrous cap rupture
APIS= Atherosclerotic Plaque Injury Score
0102030405060708090
100
Metallic n=39/88
Intact Fibrous Cap Ruptured Fibrous Cap
P=0.03
Metallic StentsMetallic Stents
Fibrous Cap Rupture: Metallic Stents
Neointimal area (µm2)
0102030405060708090
100
Beta-Estradiol* n=20/26
Intact Fibrous Cap Ruptured Fibrous Cap
P=0.19
Fibrous Cap Rupture: Beta-Estradiol Eluting Stents
Neointimal area (µm2)
Fibrous Cap Rupture: Everolimus Eluting Stents
0
20
40
60
Everolimus* n=20/21
Intact Fibrous Cap Ruptured Fibrous Cap
p=0.35
Neointimal area (µm2)
In comparison with de-novo TCFA, metallic and DES reduced lipid core and increased fibrous cap thickness.
Conclusions
stent-induced fibrous cap rupture was high and associated with increased neointimal proliferation.
However,
As a result,
New stent design reducing fibrous cap rupture may provide optimal stabilization of
thin-cap fibroatheroma
• Tradeoff between vessel injury & vessel wall apposition–Axial variability in
lesion diameter• VPSS* Designs
–Stent A–Stent B
3 mm 1.5 mm
VP with 50% Stenosis
Necrotic Core
Hypothesis: Low Force Stents May Reduce Injury & Improve Clinical
Outcomes
*VPSS: Vulnerable plaque specific stent The Guidant VP Team 2004-2005
Circumferential Stress, Cap Thickness and Stents
Cap=55 m
Cap=250 m
Loree HM, Lee RT. Circ Res 1992;71:850-858
Control Stent BStent A
Ultimate Cap Stress Threshold = 0.6
MPa1
Lendon, et al. J Biomed Eng. 1993 Jan;15(1):27-33
Vulnerable Plaque Specific Stent (VPSS) Study
Randomized Stent
Deployment
n=15The Guidant VP Team & Moreno PR. 2005
• 15 old hypercholesterolemic NZW rabbits• ASA 10 mg/kg PO (3 days before)• Anesthesia: Isofluorane 2%• Femoral arteriotomy + introducer• IV fractionated heparin: 100 u/Kg• Distal aortogram by hand injection• 3 stents/animal, random placement
• Control (1:1, stent:artery)•Stent A • Stent B
• 28 d-euthanasia (pentobarb 150 mg/kg)
Acknowledgements
Mount Sinai Medical Center• K-Raman Purushothaman, MD• Juan J. Badimon, PhD• Valentin Fuster, MD, PhD