The Holy Grail of Cardiology

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The Holy Grail of Cardiology
Vulnerable Plaques
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From Vulnerable Plaques to Vulnerable Patients

• The 1st Guideline of Association for Eradication
  of Heart Attack (AEHA) for Definition of
  Vulnerable Plaque and Vulnerable Patient
• (VP.org)

Morteza Naghavi, Erling Falk, Mohammad Madjid,
Silvio Litovsky, Ward Casscells, Renu Virmani,
James T. Willerson
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1.5 millions in the US
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Underlying pathologies of culprit coronary
lesions

• Ruptured Plaques (70)
• Stenotic (20)
• Non-stenotic (50)
• Non-Ruptured Plaques ( 30)
• Erosion
• Calcified Nodule
• Others / Unknown

MJ Davies, Circ. 1990 Falk et al. Circ. 1995
Virmani et al. ATVB 2000
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•  Terminology
• Culprit Plaque
• a Retrospective Terminology
• Vulnerable Plaque
• a Prospective Terminology

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Vulnerable Plaque

• Plaques with high likelihood of thrombosis or
  rapid progress

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Interchangeable Terminologies
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Proposed Histopathological and Clinical Criteria
for Definition of Vulnerable Plaque

•  Major Criteria
• Active Inflammation (monocyte/ macrophage
  infiltration)
• Thin Cap with Large Lipid Core
• Endothelial Denudation with Superficial Platelet
  Aggregation
• Fissured / Wounded Plaque

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Proposed Histopathological and Clinical Criteria
for Definition of Vulnerable Plaque

•  Minor Criteria
• Superficial Calcified nodule
• Glistening Yellow
• Intraplaque Hemorrhage
• Critical Stenosis
• Positive Remodeling?

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Ideal method for screening vulnerable
plaque/patient

• Non-invasive
• Inexpensive
• Accurate
• Widely Reproducible

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Proposed Histopathological and Clinical Criteria
for Definition of Vulnerable Plaque

•  Major Criteria
• Active Inflammation (monocyte/ macrophage
  infiltration)
• Thin Cap with Large Lipid Core
• Endothelial Denudation with Superficial Platelet
  Aggregation
• Fissured / Wounded Plaque

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Thermography a Novel Approach for Identification
of Vulnerable Plaques

• Mohammad Madjid, MD,
• Ward Casscells, MD,
• James T. Willerson, MD,
• Morteza Naghavi, MD

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Cardinal Signs of Inflammation
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Hypothesis

• Vascular inflammation and plaque vulnerability
  can be identified by the heat released from
  activated macrophages in the plaque.

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Temperature heterogeneity over the surface of an
endartherectomized carotid plaque
Casscells W et al. Lancet. 19963471447-51
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While macrophage/monocytes (with high metabolic
rate) density was related to higher temperature,
such a relation wasnt seen with smooth muscle
cell density (with less metabolic activity)
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Inverse relation between temperature difference
and cap thickness
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Infrared experiments show temperature
heterogeneity
Our dog model of atherosclerosis develops marked
lesions in its coronary arteries (left panel). We
observed significant temperature heterogeneity
along the coronary arteries of these dogs using
an infrared camera (right panel).
An infrared camera image shows marked temperature
heterogeneity over the surface of an
atherosclerotic carotid plaque
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Inverse correlation of pH and temperature (ºC)
in endartherectomized human carotid artery
plaques
Naghavi et al. Atherosclerosis, 2002, in press
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In vivo Studies
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Thermosensor Basket Catheter
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Dog Model of Atherosclerosis
Femoral Artery Atherosclerotic With Temperature
Heterogeneity
Carotid Artery Non-Atherosclerotic Without
Temperature Heterogeneity
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Plt0.05
Higher absolute temperature as well as
temperature heterogeneity in femoral arteries of
atherosclerotic dogs compared to their carotid
arteries which are free of disease.
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Temperature heterogeneity in atherosclerotic
lesions of Watabae rabbits
No temperature heterogeneity In aortae of normal
mice
Temperature heterogeneity In aortae of
atherosclerotic mice
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Infrared angio-thermography catheter
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Human Studies

• Our findings have been confirmed in clinical
  settings by the Hellenic group of Stefandis and
  colleagues, and also in Belgium and the
  Netherlands.

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In vivo thermal heterogeneity within human
atherosclerotic coronary arteries
Stefanadis et al. Circulation. 1999991965-71
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The risk of an adverse cardiac event in patients
with high temperature difference is significantly
higher than that in ACS patients with low
temperature difference
Stefanadis et al. J Am Coll Cardiol.
2001371277-83
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Strong correlation between C-reactive protein
(CRP) (and serum amyloid A (SAA) ) and the
temperature differences
Stefanadis et al. J Mol Cell Cardiol.
20003243-52
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• Administration of atorvastatin in patients with
  coronary artery disease results in less heat
  production from the culprit lesion and less
  temperature difference.

Stefanadis et al. Eur Heart J (in press)
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• Toutozas et al reported correlation between
  temperature and expansive remodeling and MMP-9
  concentration
• Verheye et al showed significant temperature
  heterogeneity in cholesterol fed rabbits which
  was reduced after changing from high to
  low-cholesterol diet in rabbits.

Toutouzas et al. Circulation. 2000102II-707
Toutouzas et al. J Am Coll Cardiol.
200137356A Verheye et al. Circulation Supple
Oct. 2001
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Disclosure

• Volcano Therapeutics, Inc.

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ThermaStar Catheter
Not cleared by the FDA and not available for
commercial sale.
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Center for Vulnerable Plaque ResearchHouston,
Texas
Khawar Gul, MD Said Siadaty, MD Sameh Naguib,
MD Bujin Gu, PhD Reji John, MD Basit Malik, MD KC
Courian, MD Roxana Grausu, MD
Mohammad Madjid, MD, Ward Casscells, MD, James
T. Willerson, MD, Morteza Naghavi, MD