The Art and the Science of UK General Practice A historical review and timeli...
Vp schoenhagen
1. Arterial Remodeling In Stable VersusArterial Remodeling In Stable Versus
Unstable Coronary Syndromes:Unstable Coronary Syndromes:
An Intravascular Ultrasound StudyAn Intravascular Ultrasound Study
Arterial Remodeling In Stable VersusArterial Remodeling In Stable Versus
Unstable Coronary Syndromes:Unstable Coronary Syndromes:
An Intravascular Ultrasound StudyAn Intravascular Ultrasound Study
Paul Schoenhagen, MD,FAHAPaul Schoenhagen, MD,FAHA
Steven E Nissen, MD,FACCSteven E Nissen, MD,FACC
E Murat Tuzcu, MD,FACCE Murat Tuzcu, MD,FACC
The Cleveland Clinic FoundationThe Cleveland Clinic Foundation
Paul Schoenhagen, MD,FAHAPaul Schoenhagen, MD,FAHA
Steven E Nissen, MD,FACCSteven E Nissen, MD,FACC
E Murat Tuzcu, MD,FACCE Murat Tuzcu, MD,FACC
The Cleveland Clinic FoundationThe Cleveland Clinic Foundation
2. BackgroundBackground
• Originally, Glagov described arterial remodeling as anOriginally, Glagov described arterial remodeling as an
increase in external elastic membrane area withinincrease in external elastic membrane area within
atherosclerotic lesions.atherosclerotic lesions.
• In early CAD, remodeling maintains lumen area despiteIn early CAD, remodeling maintains lumen area despite
increasing plaque burden.increasing plaque burden.
• Although first observed in necropsyAlthough first observed in necropsy studiesstudies, remodeling, remodeling
has been confirmedhas been confirmed in vivoin vivo by intravascular ultrasound.by intravascular ultrasound.
• The relationship between remodeling and various clinicalThe relationship between remodeling and various clinical
ischemic syndromes remains uncertain.ischemic syndromes remains uncertain.
4. Objectives and Study DesignObjectives and Study Design
•• Retrospectively analyze intravascular ultrasoundRetrospectively analyze intravascular ultrasound
images in a series of patients with either stable anginaimages in a series of patients with either stable angina
or recent onset of unstable symptomatology.or recent onset of unstable symptomatology.
•• Examine the relationship between clinical presentationExamine the relationship between clinical presentation
and plaque features at the culprit lesion, including:and plaque features at the culprit lesion, including:
• Presence, direction and extent of arterial remodelingPresence, direction and extent of arterial remodeling
• Plaque morphology (echogenicity)Plaque morphology (echogenicity)
• Plaque eccentricityPlaque eccentricity
5. Methods: PatientsMethods: Patients
Patients with pre-interventionalPatients with pre-interventional
ultrasound of native coronary arteriesultrasound 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
6. Methods: Image AnalysisMethods: Image Analysis
• Intravascular ultrasound images obtained from aIntravascular 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:
MaximumMaximum -- Minimum Plaque ThicknessMinimum Plaque Thickness
Maximum Plaque ThicknessMaximum Plaque Thickness
xx 100100
17. LimitationsLimitations
• Selection bias:Selection bias:
– The cohort included only relatively severe lesionsThe cohort included only relatively severe lesions
selected for pre-interventional ultrasound imaging.selected for pre-interventional ultrasound imaging.
• Presence of ultrasound catheter within severePresence of ultrasound catheter within severe
lesions may alter vessel geometry.lesions may alter vessel geometry.
• Classification of plaque morphology based uponClassification of plaque morphology based upon
subjective visual criteria.subjective visual criteria.
18. ConclusionConclusion
• Significant differences in ultrasound characteristicsSignificant differences in ultrasound characteristics
between 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 clinicalA 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 moreHypothesis: Bulky remodeled plaques may be more
vulnerable to mechanical forces, thus leading to plaquevulnerable to mechanical forces, thus leading to plaque
rupture and acute coronary syndromes.rupture and acute coronary syndromes.
19. 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
20. Coronary RemodelingCoronary Remodeling
ProgressioProgressio
nn
EEM shrinkageEEM shrinkage
NormalNormal
vesselvessel
MinimalMinimal
CADCAD
EEM expansionEEM expansion Lumen shrinkageLumen shrinkage
SevereSevere
CADCAD
ModerateModerate
CADCAD
SevereSevere
CADCAD
Period of Instability?Period of Instability?
Regression?Regression?
Schoenhagen et al. JACC 2001;38:297-306
Editor's Notes
Slide 1:
In this presentation we will describe the remodeling response of coronary culprit lesions in patients presenting with stable and unstable coronary syndromes.
The results are published in Circulation 2000;101:598-603
Slide 2:
Originally, Dr. Glagov described arterial remodeling as an increase in the external elastic membrane area within atherosclerotic coronary lesions.
In early coronary artery disease, remodeling maintains the lumen area despite increasing plaque burden.
Although first observed in necropsy studies, remodeling has been confirmed in vivo by intravascular ultrasound.
The relationship between arterial remodeling and various clinical ischemic syndromes remains uncertain.
Slide 3:
Intravascular ultrasound (IVUS) is a tomographic imaging modality showing lumen and vessel wall. It allows the direct observation of coronary plaque characteristics and development.
Slide 4:
The objective of our study was to analyze intravascular ultrasound images in a series of patients with either stable angina or recent onset of unstable symptomatology.
We intended to examine the relationship between clinical presentation and plaque features at the culprit lesion, including:
-Presence, direction and extent of arterial remodeling.
-Plaque morphology and
-Plaque eccentricity.
Slide 5: This slide shows the study population: 216 patients with preinterventional ultrasound of native coronary arteries were identified.
85 patients were excluded from the study because of poor image quality, lesion location or heavy calcification.
The study group of 131 patients included 85 patients with unstable and 46patients with stable presentation.
In the unstable group 79 patients had unstable angina and 9 patients had an acute myocardial infarction.
In the stable group 37 patients had stable angina pectoris and 9 patients were asymptomatic but had objective evidence of ischemia.
Slide 6:
Intravascular ultrasound images were obtained from a proximal reference site and the culprit lesion site, which was defined as the site with the greatest luminal narrowing.
Quantitative variables analyzed included the external elastic membrane area, the lumen area and the plaque area.
The plaques were classified according to their predominant morphology as echolucent, echodense, mixed or calcified.
The axial distribution of the plaque was described by the eccentricity index, which was defined as: maximum minus minimum plaque thickness divided by maximum plaque thickness times 100.
Slide 7:
Arterial remodeling was described by the remodeling index and remodeling category.
This slide shows the definitions used in our study and illustrates them by the accompanying figures.
The remodeling index was calculated by dividing the external elastic membrane area at the lesion site by the external elastic membrane area of the proximal reference site.
Positive remodeling was defined as a remodeling index greater than 1.05 and negative remodeling by a remodeling less than 0.95.
Slide 8:
This slide exemplifies the calculation of the remodeling index for a lesion with positive remodeling. It shows the IVUS image of the proximal reference on the left and that of the lesion site on the right. The remodeling index is calculated by dividing the EEM area at the lesion site by the EEM area at the proximal reference site and is, in this example, 1.27.
Slide 9:
This slide exemplifies the calculation of the remodeling index for a lesion with negative remodeling. The remodeling index in this example is 0.72.
Slide 10:
This table shows the clinical and demographic features of the patient population: There was no significant difference between the stable and unstable group regarding age, gender and lesion location.
Slide 11:
This table shows the distribution of risk factors for coronary artery disease between the stable and unstable group.
There was no significant difference in the frequency of diabetes, hypertension, hyperlipidemia, smoking and positive family history.
Slide 12:
The quantitative intravascular ultrasound measurements are shown in this table:
At the proximal reference site there was no significant difference between the stable and unstable group regarding the plaque area, EEM area and percent area reduction.
At the lesion site, percent area reduction was also similar between the two groups, but the plaque area and the EEM area were significantly larger in the unstable than in the stable group.
The Remodeling Index was also significantly larger in the unstable group. It was 1.06 in the unstable and 0.94 in the stable group. The difference was highly significant with a p-value of 0.008.
Slide 13:
This slide shows the frequency of positive and negative remodeling in the stable and unstable group.
The remodeling category is shown on the horizontal axis and the frequency of each category in the stable and unstable group is shown on the vertical axis.
We found positive remodeling to be significantly more common in the unstable group. 52% of patients in the unstable but only 20% in the stable group had positive remodeling at the lesion site.
Negative remodeling was significantly more common in the stable group. It was found in 56% of patients in the stable but only 32% of the unstable group.
.
Slide 14:
This slide shows the plaque morphology in the the stable and unstable group.
The predominant morphology is shown on the horizontal axis and the frequency of each morphology in the stable and unstable group is shown on the vertical axis.
The frequency of echolucent plaques was significantly higher in the unstable group. We found echolucent plaques in 19% of the unstable lesions but in only 4% of the stable lesions.
The frequency of the other categories was similar between the two groups.
.
In addition to the data shown, we also compared lesion eccentricity between the unstable and stable group. We found no difference in the eccentricity index between the two groups.
Slide 15:
This slide exemplifies the association between stable clinical presentation and negative remodeling. It shows the IVUS image of the proximal reference on the left and that of the lesion site on the right.
The patient presented with stable angina pectoris.
The lesion shows mixed morphology and negative remodeling with a remodeling index of 0.71.
Slide 16:
On the other hand, this slide exemplifies the association between unstable clinical presentation and positive remodeling.Again, it shows the proximal reference on the left and the lesion site on the right.
The patient presented with an acute myocardial infarction.
The plaque has a echolucent morphology and a irregular surface structure suggesting plaque rupture. The lesion shows positive remodeling with a remodeling index of 1.42.
Slide 17:
The results of our study are limited for several reasons:
The cohort included only relatively severe lesions selected for pre-interventional intravascular ultrasound imaging of the culprit lesion.
The presence of the ultrasound catheter within severe lesions might have altered the vessel geometry.
The classification of the plaque morphology is based upon subjective visual criteria.
Slide 18:
In conclusion, we found significant differences in ultrasound characteristics between unstable and stable lesions:
Although luminal narrowing was similar between the two groups, unstable lesions had greater plaque burden and a larger extent of arterial remodeling.
A prospective study of the relationship between clinical presentation and plaque morphology is warranted to examine the hypothesis, that bulky remodeled plaques are more vulnerable to mechanical forces, thus leading to plaque rupture and acute coronary syndromes.
Slide 19:
Our study is one of several recent IVUS and histologic reports describing the relation between arterial remodeling and clinical presentation in different patient populations.
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Slide 20:
These studies demonstrate the complex interactions between plaque burden, remodeling and instability of atherosclerotic lesion.
During this ACC meeting we will present data examining the remodeling response of mildly-stenotic coronary lesions.