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Arterial Remodeling In Stable Versus Unstable Arterial Remodeling In Stable Versus Unstable Coronary Syndromes: Coronary Syndromes:
An Intravascular Ultrasound StudyAn Intravascular Ultrasound Study
Paul Schoenhagen, MD,FAHAPaul Schoenhagen, MD,FAHA
Steven E Nissen, MD,FACCSteven E Nissen, MD,FACCE Murat Tuzcu, MD,FACCE Murat Tuzcu, MD,FACC
The Cleveland Clinic FoundationThe Cleveland Clinic Foundation
BackgroundBackground
• Originally, Glagov described arterial remodeling as an Originally, Glagov described arterial remodeling as an increase in external elastic membrane area within increase in external elastic membrane area within atherosclerotic lesions.atherosclerotic lesions.
• In early CAD, remodeling maintains lumen area despite In early CAD, remodeling maintains lumen area despite increasing plaque burden.increasing plaque burden.
• Although first observed in necropsy Although first observed in necropsy studiesstudies, remodeling , remodeling has been confirmed has been confirmed in vivoin vivo by intravascular ultrasound. by intravascular ultrasound.
• The relationship between remodeling and various clinical The relationship between remodeling and various clinical ischemic syndromes remains uncertain.ischemic syndromes remains uncertain.
Intravascular Ultrasound
vessel wall/ plaquelumen
IVUS Catheter
Objectives and Study DesignObjectives and Study Design
• • Retrospectively analyze intravascular ultrasound images in a Retrospectively analyze intravascular ultrasound images in a series of patients with either stable angina or recent onset of series of patients with either stable angina or recent onset of unstable symptomatology.unstable symptomatology.
• • Examine the relationship between clinical presentation and plaque Examine the relationship between clinical presentation and plaque features at the culprit lesion, including:features at the culprit lesion, including:
• Presence, direction and extent of arterial remodeling Presence, direction and extent of arterial remodeling
• Plaque morphology (echogenicity)Plaque morphology (echogenicity)
• Plaque eccentricityPlaque eccentricity
Methods: PatientsMethods: PatientsPatients with pre-interventional Patients with pre-interventional
ultrasound of native coronary arteries ultrasound of native coronary arteries (n=216)(n=216)
Excluded (n=85)
Study Patients (n=131)Study Patients (n=131)
Stable (n=46)Stable (n=46)Stable Angina (n=37)Stable Angina (n=37)
(+) ETT (n=9)(+) ETT (n=9)
Unstable (n=85)Unstable (n=85)Unstable Angina (n=76) Unstable Angina (n=76)
Acute MI (n=9)Acute MI (n=9)
Ostial or bifurcation lesions, Ostial or bifurcation lesions, heavy calcium, image qualityheavy calcium, image quality
Methods: Image AnalysisMethods: Image Analysis
• Intravascular ultrasound images obtained from a Intravascular ultrasound images obtained from a proximal reference site and culprit lesion site.proximal reference site and culprit lesion site.
• Quantitative variables:Quantitative variables:
– EEM area, lumen area, and plaque areaEEM area, lumen area, and plaque area
• Plaque morphology:Plaque morphology:
– Echolucent, echodense, mixed, calcifiedEcholucent, echodense, mixed, calcified
• Eccentricity Index:Eccentricity Index:Maximum Maximum -- Minimum Plaque ThicknessMinimum Plaque Thickness
Maximum Plaque ThicknessMaximum Plaque Thickness xx 100100
Positive Remodeling
Culprit Lesion
EEM Contour
ProximalReference
ProximalReference
Direction of Arterial RemodelingDirection of Arterial Remodeling
Schoenhagen et al. Circulation 2000; 101:598-603
Negative Remodeling
Culprit Lesion
EEM Contour
Remodeling Ratio (RR) = EEM area lesion / EEM area proximal reference
Negative RemodelingRR < 0.95
Positive RemodelingRR > 1.05
Example: Positive RemodelingExample: Positive Remodeling
RemodelingRemodeling IndexIndex == 18.918.9 mmmm22
14.914.9 mmmm22 == 1.271.27
Proximal Reference Lesion
EEM = 14.9 mm2 EEM = 18.9 mm2
Example: Negative RemodelingExample: Negative Remodeling
Proximal ReferenceProximal Reference LesionLesion
EEMEEM = 16.0 mm = 16.0 mm22 EEMEEM = 11.5 mm = 11.5 mm22
RemodelingRemodeling IndexIndex == 11.511.5 mmmm22
16.016.0 mmmm22 == 0.720.72
Clinical and Demographic FeaturesClinical and Demographic Features
Stable (n = 46)Stable (n = 46) Unstable (n = 85)Unstable (n = 85)
p = NS for all characteristics
AgeAge 62.6 years62.6 years 59.5 Years59.5 Years
MaleMale 71.7 %71.7 % 64.7 % 64.7 %
FemaleFemale 28.3%28.3% 35.3 %35.3 %
LADLAD 56.6%56.6% 51.8%51.8%
LCxLCx 21.7%21.7% 17.6%17.6%
RCARCA 21.7%21.7% 30.6%30.6%
Clinical and Demographic CharacteristicsClinical and Demographic Characteristics
SSttaabblle (e (nn=4=466)) UUnsnsttaabblle (e (nn==885)5)
DiDiaabbeteteess 226.6.11%% 119.9.77%%
HHypypeerrtteennsisioonn 447.7.88%% 663.3.22%%
HHypypeerrlilippidideemimiaa 446.6.77%% 550.0.00%%
SSmomokikinngg 552.2.22%% 660.0.55%%
CCAAD FaD Fammilily y HHisisttoorryy 226.6.11%% 228.8.99%%
Risk Factors for Coronary Artery Disease
p = NS for all characteristics
Reference and Lesion MeasurementsReference and Lesion Measurements
Stable Unstable p value
Proxima l Re ferencePlaque Area 6.20 mm2 6.10 mm2 NS
EEM Area 14.1 mm2 15.2 mm2 NS
% Area Reduction 42.3 40.3 NS
Target LesionPlaque Area 11.1±4.8 mm2 13.9±5.5 mm2 0.005
EEM Area 13.0±4.8 mm2 16.1±6.2 mm2 .04% Area Reduction 83.1±6.7 85.0+6.4 NS
Remodeling Index 0.94 1.06 0 .008
Results: Extent of RemodelingResults: Extent of Remodeling
00
2020
4040
6060
Percentof
Cohort
PositiveRemodeling
Absence ofRemodeling
NegativeRemodeling
Unstable
Stable
*p=0.0003 *p=0.3 *p=0.006
Schoenhagen et al. Circulation 2000; 101:598-603
Results: Plaque MorphologyResults: Plaque Morphology
0
10
20
30
40
Percentof
Cohort
Echolucent Echodense Mixed Calcified
UnstableStable
p=0.02 p=0.4 p=1.0 p=0.3
Schoenhagen et al. Circulation 2000; 101:598-603
Stable Presentation and Negative RemodelingStable Presentation and Negative Remodeling
Proximal ReferenceProximal Reference LesionLesion
EEMEEM = 10.5 mm = 10.5 mm22 EEMEEM = 7.5 mm = 7.5 mm22
Mixed Morphology with Remodeling Index = 0.71
Schoenhagen et al. Circulation 2000; 101:598-603
Unstable Presentation: Positive RemodelingUnstable Presentation: Positive RemodelingEcholucent Plaque with Remodeling Index = 1.42
Proximal ReferenceProximal Reference
EEMEEM = 14.3 mm = 14.3 mm22 EEMEEM = 20.3 mm = 20.3 mm22
Culprit LesionCulprit Lesion
Schoenhagen et al. Circulation 2000; 101:598-603
LimitationsLimitations
• Selection bias:Selection bias:– The cohort included only relatively severe lesions The cohort included only relatively severe lesions
selected for pre-interventional ultrasound imaging.selected for pre-interventional ultrasound imaging.
• Presence of ultrasound catheter within severe Presence of ultrasound catheter within severe lesions may alter vessel geometry.lesions may alter vessel geometry.
• Classification of plaque morphology based upon Classification of plaque morphology based upon subjective visual criteria.subjective visual criteria.
ConclusionConclusion
• Significant differences in ultrasound characteristicsSignificant differences in ultrasound characteristicsbetween unstable and stable lesions:between unstable and stable lesions:
– Greater plaque burden despite similar luminal narrowingGreater plaque burden despite similar luminal narrowing
– Greater extent of positive remodelingGreater extent of positive remodeling
• A prospective study of the relationship between clinical A prospective study of the relationship between clinical presentation and plaque morphology is warranted:presentation and plaque morphology is warranted:
– Hypothesis: Bulky remodeled plaques may be more Hypothesis: Bulky remodeled plaques may be more vulnerable to mechanical forces, thus leading to plaque vulnerable to mechanical forces, thus leading to plaque rupture and acute coronary syndromes.rupture and acute coronary syndromes.
Remodeling and Clinical PresentationRemodeling and Clinical Presentation
Stable and Unstable
Syndromes and
Remodeling:
IVUS
Pathology
Smits et al.
Schoenhagen et al.
Nakamura et al.
Filardo et al.
Nishioka et al.
Alibelli-Chemarin et al.
Burke et al.
Varnava et al.
Cardiovas. Res.’99;41:458-464
Circulation ‘00;101:598-603
J Am Coll Cardiol ‘01;37:63-9
Am J Cardiol ‘00;85:760-762
JACC ‘97;29:125A, abstract
JACC ‘98;31:276A, abstract
Circulation ’02;105:297-303
Circulation ’02;105:939-943
Coronary RemodelingCoronary RemodelingProgressionProgression
EEM shrinkageEEM shrinkage
NormalNormalvesselvessel
MinimalMinimalCADCAD
EEM expansionEEM expansion Lumen shrinkageLumen shrinkage
SevereSevereCADCAD
ModerateModerateCADCAD
SevereSevereCADCAD
Period of Instability?Period of Instability?
Regression?Regression?
Schoenhagen et al. JACC 2001;38:297-306
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