142 arterial remodelling in coronary syndromes
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This study used intravascular ultrasound to examine arterial remodeling and plaque characteristics in 131 patients with either stable angina or recent unstable symptoms. Patients with unstable presentations had greater plaque burden at the culprit lesion despite similar luminal narrowing, and a greater extent of positive arterial remodeling compared to those with stable angina. The culprit lesions in unstable patients also showed a higher rate of echolucent plaque morphology. These findings suggest that larger plaque burdens with positive remodeling may render lesions more prone to rupture and acute coronary syndromes in unstable patients.
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142 arterial remodelling in coronary syndromes
- 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.
- 3. Intravascular UltrasoundIntravascular Ultrasound vessel wall/ plaquelumen IVUS Catheter
- 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
- 7. Positive Remodeling Culprit Lesion EEM Contour Proximal Reference Proximal Reference Direction of Arterial RemodelingDirection of Arterial Remodeling Schoenhagen et al. Circulation 2000; 101:598-603 Negative Remodelin g Culprit Lesion EEM Contour Remodeling Ratio (RR) = EEM area lesion / EEM area proximal reference Negative Remodeling RR < 0.95 Positive Remodeling RR > 1.05
- 8. Example: Positive RemodelingExample: Positive Remodeling RemodelingRemodelingIndexIndex == 18.918.9 mmmm22 14.914.9 mmmm22 == 1.271.27 Proximal Reference Lesion EEM = 14.9 mm2 EEM = 18.9 mm2
- 9. Example: Negative RemodelingExample: Negative Remodeling Proximal ReferenceProximal Reference LesionLesion EEMEEM = 16.0 mm= 16.0 mm22 EEMEEM = 11.5 mm= 11.5 mm22 RemodelingRemodelingIndexIndex == 11.511.5 mmmm22 16.016.0 mmmm22 == 0.720.72
- 10. 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%
- 11. 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 Fammililyy HHisisttoorryy 226.6.11%% 228.8.99%% Risk Factors for Coronary Artery Disease p = NS for all characteristics
- 12. Reference and Lesion MeasurementsReference and Lesion Measurements Stable Unstable p value Proximal Reference Plaque 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 Lesion Plaque 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
- 13. Results: Extent of RemodelingResults: Extent of Remodeling 00 2020 4040 6060 Percent of Cohort Positive Remodeling Absence of Remodeling Negative Remodeling Unstable Stable *p=0.0003 *p=0.3 *p=0.006 Schoenhagen et al. Circulation 2000; 101:598-603
- 14. Results: Plaque MorphologyResults: Plaque Morphology 0 10 20 30 40 Percent of Cohort Echolucent Echodense Mixed Calcified Unstable Stable p=0.02 p=0.4 p=1.0 p=0.3 Schoenhagen et al. Circulation 2000; 101:598-603
- 15. 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
- 16. Unstable Presentation: Positive RemodelingUnstable Presentation: Positive Remodeling Echolucent 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
- 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.
- &lt;number&gt; 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.