142 arterial remodelling in coronary syndromes

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


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


Stable Presentation and Negative RemodelingStable Presentation and Negative Remodeling

Proximal ReferenceProximal Reference LesionLesion


Mixed Morphology with Remodeling Index = 0.71


Unstable Presentation: Positive RemodelingUnstable Presentation: Positive RemodelingEcholucent Plaque with Remodeling Index = 1.42

Proximal ReferenceProximal Reference


Culprit LesionCulprit Lesion


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

Health & Medicine

142 arterial remodelling in coronary syndromes