Vulnerable Plaque

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Vulnerable Plaque

• Simon Redwood
• St Thomas Hospital, London

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Definitions of Vulnerable Plaque

• Functional Definition
• A plaque, often non-stenotic, that has a high
  likelihood of becoming disrupted and forming a
  thrombogenic factor after exposure to an acute
  risk factor
• Histological Definition
• Plaque containing a thin fibrous cap, lipid pools
  and macrophages
• Prospective Definition
• A signature that has been proven in a prospective
  study to identify a plaque that is prone to
  disrupt and can be recognised and measured in the
  cath lab

James Muller
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Vulnerable Plaque

• The impact of early vulnerable plaque
  detection and therapy would be a major
  breakthrough in the management of patients with
  coronary, peripheral and neurovascular disease!!!

Thin fibrous cap lipid core dense macrophages
Plaque rupture
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Morphology vs. Activity Imaging
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Thermal detection of cellular infiltrates in
living atherosclerotic plaques possible
implications for plaque rupture and thrombosis
50 Carotid endarterectomy samples
Casscells et al. Lancet 1996251447-1451
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Thermal heterogeneity within human
atherosclerotic coronary arteries detected in
vivo A new method of detection by application of
a special thermography catheter
45 controls 15 stable angina 15 unstable angina
unresponsive to Rx 15 AMI within 6 hrs
Stefanadis et al. Circulation 1999201965-1971
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Increased local temperature in human coronary
atherosclerotic plaques an independent predictor
of clinical outcome in patients undergoing a
percutaneous coronary intervention
Stefanadis et al. JACC 2001371277-1283
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Statin treatment is associated with reduced
thermal heterogeneity in human atherosclerotic
plaques
Stefanadis et al. EHJ 2002231664-1669
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Figure 1. Severe stenosis in the mid left
anterior descending artery
Figure 2. The Volcano Thermography Catheter
Basket with five peripheral thermistors and one
central sensor.
Figure 3 An example of temperature measurements
at the site of a left anterior descending artery
plaque. The mid vessel temperature, and the
variations from this at the sites of apposition
of the peripheral sensors, are displayed
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Intravascular Elastography/ Palpography
The response of tissue to compression is a
function of its mechanical properties and
composition In vitro related to composition
Thoraxcentre, Rotterdam
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Virtual Histology
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Controversies

• Vulnerable Plaque
• Is it an outdated concept?
• Which plaques cause events?

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Vulnerable Plaque

• An Outdated Concept??

More important to identify patients in whom
disruption of a vulnerable plaque is likely to
result in a clinical event The Vulnerable
Patient
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Diffuse VulnerabilityVulnerable Arterial Bed
24 patients with ACS, 72 arteries explored with
IVUS
80 of ACS patients have gt 1 ruptured plaque
Patients ()
Number of ruptured plaques in addition to
culprit lesion
Rioufol et al. , Circulation 2002 106804-808
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Clinical Outcomes After PCI
One-year FU for Adverse Clinical Events
Percent of Events
ACS (N2,971)
P0.0007
Non-ACS (N5,051)
P0.0008
19.0
13.2
15.9
P0.0013
PNS
10.6
4.2
4.7
4.6
2.8
Death
MI
Non-TVR
Death/MI/Non-TVR
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Widespread coronary inflammation in unstable
angina

• Neutrophil myeloperoxidase measured in 5 groups
  of patients
• LAD (n24) and RCA (n9) unstable angina
• Stable angina (n13)
• Variant angina with recurrent ischaemia (n13)
• Controls (n6)
• Aorta and great cardiac vein sampling
• Drains LAD territory

Buffon et al. (Maseri) New Engl J Med 2002 347
5-12
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Vulnerable Coronary Arterial Bed

• Sampling in the coronary sinus
• A-V difference in Myeloperoxidase index

Buffon et al. New Engl J Med 2002 347 5-12
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Transcardiac Cytokine Gradient
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Plt0.01

• 38 pts with Braunwald IIIb UA
• Time from symptom onset 8.6 5.7 hrs
• Simultaneous aorta and coronary sinus sampling
• Divided according to troponin status

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Pns
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IL-6 (ng/mL)
4
0
All Patients
TnT ve
TnT -ve
Cusack Redwood JACC 2002391917-23
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Stefanadis et al. Circulation 1999201965-1971
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• 54 year old male
• Admitted with 6 hours intermittent pain
• Troponin-T positive
• Dynamic inferior ST/T changes

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Aalst
Stefanadis
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Serological Markers of VulnerabilityReflecting
Metabolic and Immune Disorders

• Lipoprotein profile
• High LDL, low HDL, Lp-A, lipid peroxidation
  (ox-LDL, ox-HDL), etc
• Markers of inflammation
• hsCRP, IL-6, CD40L, ICAM-1, VCAM-1, P-selectin,
  leucocytosis, anti-LDL Ab, anti-HSP Ab, etc
• Markers of metabolic syndrome
• eg diabetes, hypertriglyceridaemia
• Others
• Homocysteine, PAPP-A, ADMA, DDAH, NEFA

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Serological Markers of VulnerabilityReflecting
Hypercoagulability

• Blood Hypercoagulability
• Fibrinogen, d-dimer, factor V leiden, factors V,
  VII, VIII, XIII, von Willebrand factor, protein S
  and C, thrombomodulin, antithrombin III
• Transient factors smoking, dehydration,
  infection, cocaine, postprandial, etc
• Platelet activation/ aggregation
• Gene polymorphisms of IIb/IIIa, Ia/IIa, Ib/IX
• Other
• Anticardiolipin Abs, thrombocytosis, sickle,
  polycythaemia, diabetes, hypercholesterolaemia,
  hyperhomocysteinaemia, etc

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Which Plaques Cause ACS?
Falk, Shah and Fuster, Circulation 1995
Acute Coronary Syndromes most often occur at the
site of mild stenoses
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Which Plaques Cause ACS?

• A few small studies
• Retrospective
• Selection bias
• No QCA or IVUS
• Visual estimation
• Variable follow-up
• Likely that many mild stenoses progressed prior
  to occlusion

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Coronary Occlusion at 5 Years as a Function of
Initial Stenosis Severity
Alderman et al, JACC 93
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Long-term Follow-up After PTCA was Deferred Based
on IVUS Findings

• 357 lesions
• 13 month follow-up
• Independent predictors of MACE
• IVUS MLA
• IVUS AS

Abizaid, Circ 99
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Severity of Atherosclerosis at Sites of Plaque
Rupture with Occlusive Thrombus

• Autopsy data
• 182 patients who died from AMI
• Plaque rupture with occlusive thrombus occurs at
  the site of tight stenoses

Qiao, JACC 91
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Risk of Coronary Events Increases with the
Severity of Luminal Narrowing
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FFR for Risk Stratification of Patients with an
Intermediate Stenosis

• 107 patients
• SA or UA (I or II)
• 40-70 stenosis on angio (in addition to treated
  lesion)
• No perfusion defect on SPECT
• 1 year follow-up
• Divided according to FFR gt or lt 0.75

Chamuleau et al, AJC 2002 89 377-380
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Conclusions

• Imaging vulnerable plaques is a fascinating
  research tool providing useful insights into the
  pathophysiology of ACS
• At present, it has little clinical use
• Local therapy, in the absence of documented
  ischaemia, is unproven

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Conclusions

• Risk stratification should be based on ischaemia
  detection, markers of necrosis, inflammation and
  thrombogenicity
• All patients should have systemic therapy aimed
  at stabilising plaques
• Aspirin/ clopidogrel/ IIbIIIa antagonists
• B blockers and ACE inhibitors
• High dose statins