Title: The Holy Grail of Cardiology
1The Holy Grail of Cardiology
Vulnerable Plaques
2From 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
31.5 millions in the US
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5Underlying 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
6- Terminology
- Culprit Plaque
- a Retrospective Terminology
- Vulnerable Plaque
- a Prospective Terminology
7Vulnerable Plaque
- Plaques with high likelihood of thrombosis or
rapid progress
8Interchangeable Terminologies
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10Proposed 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
11Proposed Histopathological and Clinical Criteria
for Definition of Vulnerable Plaque
- Minor Criteria
- Superficial Calcified nodule
- Glistening Yellow
- Intraplaque Hemorrhage
- Critical Stenosis
- Positive Remodeling?
12Ideal method for screening vulnerable
plaque/patient
- Non-invasive
- Inexpensive
- Accurate
- Widely Reproducible
13Proposed 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
14Thermography a Novel Approach for Identification
of Vulnerable Plaques
- Mohammad Madjid, MD,
- Ward Casscells, MD,
- James T. Willerson, MD,
- Morteza Naghavi, MD
15Cardinal Signs of Inflammation
16Hypothesis
-
- Vascular inflammation and plaque vulnerability
can be identified by the heat released from
activated macrophages in the plaque.
17Temperature heterogeneity over the surface of an
endartherectomized carotid plaque
Casscells W et al. Lancet. 19963471447-51
18While 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)
19Inverse relation between temperature difference
and cap thickness
20Infrared 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
21Inverse correlation of pH and temperature (ºC)
in endartherectomized human carotid artery
plaques
Naghavi et al. Atherosclerosis, 2002, in press
22In vivo Studies
23Thermosensor Basket Catheter
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25Dog Model of Atherosclerosis
Femoral Artery Atherosclerotic With Temperature
Heterogeneity
Carotid Artery Non-Atherosclerotic Without
Temperature Heterogeneity
26Plt0.05
Higher absolute temperature as well as
temperature heterogeneity in femoral arteries of
atherosclerotic dogs compared to their carotid
arteries which are free of disease.
27Temperature heterogeneity in atherosclerotic
lesions of Watabae rabbits
No temperature heterogeneity In aortae of normal
mice
Temperature heterogeneity In aortae of
atherosclerotic mice
28Infrared angio-thermography catheter
29Human Studies
- Our findings have been confirmed in clinical
settings by the Hellenic group of Stefandis and
colleagues, and also in Belgium and the
Netherlands.
30In vivo thermal heterogeneity within human
atherosclerotic coronary arteries
Stefanadis et al. Circulation. 1999991965-71
31The 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
32Strong correlation between C-reactive protein
(CRP) (and serum amyloid A (SAA) ) and the
temperature differences
Stefanadis et al. J Mol Cell Cardiol.
20003243-52
33- 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)
34- 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
35Disclosure
- Volcano Therapeutics, Inc.
36ThermaStar Catheter
Not cleared by the FDA and not available for
commercial sale.
37Center 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