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Coronary Artery Coronary Artery ThermographyThermography
Christodoulos StefanadisProfessor of CardiologyAthens Medical School
The 10th Anniversary, Interventional Vascular Therapeutics Angioplasty Summit
2005 TCT Asia Pacific
••Thin capThin cap••Lipid coreLipid core••Positive remodelingPositive remodeling••Reduction of smooth muscle cellsReduction of smooth muscle cells••MacrophagesMacrophages Eur Heart J 2004;25(12):1077-1082
Santorini Congress Conclusions
In the search for vulnerable plaqueWhat???
InflammationInflammation –– AtheromatosisAtheromatosis
Can we detect the vulnerable plaque?
Technique Fibrous cap Lipid core Inflammation Calcium Thrombus VV
NO IDEAL METHODNO IDEAL METHOD
IVUS + ++ - +++ + -Angioscopy + ++ - - +++ -OCT +++ +++ + +++ + -MRI + ++ + ++ + -IVUS+contrast + ++ + ++ + ++?Thermography - - +++ - - -
ThermographyThermography
The Fire Within
Casscells et al, Lancet 1996
Medispes System
Thermocore System
RADI System
Volcano System
Thermal Heterogeneity in Thermal Heterogeneity in Atherosclerotic PlaquesAtherosclerotic Plaques
Plaque Thermography
• What do we measure?
Thermal Heterogeneity –InflammatoryIn vivo experimental study
Verheye et al, Circulation 2002;105(13):1596-601
ControlControl
AtheromatousAtheromatous
1.2oC
Ex vivo measurements
In 27 patients with carotid stenosis: In endarterectomyspecimens histology was correlated with temperature
measurements
Correlation of Histology Correlation of Histology –– TemperatureTemperatureEx Vivo in Carotid PlaquesEx Vivo in Carotid Plaques
Madjid M, Naghavi M, et al. Am J Cardiol 2002;90:36-39
Correlation of human human coronary plaque temperature measurements with the presence of inflammatory markers in pathology examination
Milan-Athens Experience
0% concentration of macrophage marker CD0% concentration of macrophage marker CD--68 68
+ 0.+ 0.0101°°CC
Patient With Thermal Heterogeneity Patient With Thermal Heterogeneity (TD: 0.08(TD: 0.08ooC)C)
Milan-Athens Experience
Correlation of human human coronary plaque temperature measurements with the presence of inflammatory markers in pathology examination
20% concentration of macrophage marker CD20% concentration of macrophage marker CD--68 68
+ 0.+ 0.0808°°CC
0
.2
.4
.6
.8
1
0 10 20 30CRP (mg/dl)
∆T (O
C)
Correlation of human human coronary plaque temperature measurements with systemic
inflammatory markers
Stefanadis et al. J Mol Cell Cardiol 2000
Angiogenesis in vasa vasorum
Herrmann et al. Cardiovasc Res 2001;51:762-6
Control 2 weeks hyperlipidemic diet 6 weeks No endothelial dysfunction Endothelial dysfunction
Vasa vasorum development is observed prior to endothelial dysfunction
Vasa Vasorum
Experimental ProtocolEffect of Vasa Vasorum on Plaque Temperature
37,6
37,8
38
38,2
38,4
38,6
38,8
39Te
mpe
ratu
re (o C
)
Without VV VV
Athens Medical School
Plaque Thermography
• What do we measure?
• Inflammation• Neovascularization
Thermography
Coronary ArteryCoronary Artery Coronary SinusCoronary Sinus
Thermal Heterogeneity and Diabetes Mellitus Type 2
An Increased Inflammatory Activation?
Clinical Studies
Diabetes Mellitus and Temperature Measurements
0
0,05
0,1
0,15
0,2
DM non-DM
∆T (O
C)
P = 0.01
Toutouzas K, et al. Diabetes Care in press
Diabetes Mellitus and Temperature Measurements
Diabetic patients with ACS have higher thermal heterogeneity compared to non diabetic patients
P = 0.02 P = 0.67
Toutouzas K, et al. Diabetes Care in press
Prolonged Thermal Heterogeneity Post ACS
A Prolonged Inflammatory Activation?
Prolonged thermal heterogeneity post MI
Toutouzas K et al, Am Heart J 2004
0
.1
.2
.3
.4
.5
.6
.7
.8
.9U
nits
DT
SA
A MI
DT
(o C)
MI > 2 months Stable AnginaN=56
Prolonged inflammation
Prognostic implication of Prognostic implication of detection of vulnerable plaque detection of vulnerable plaque
StentingStenting in in ‘‘HotHot’’ PlaquesPlaques
=
Cold plaqueCold plaque Hot plaqueHot plaque
Temperature and Prognosis post PCI
FV
EventNo Event
2.0
1.5
1.0
0.5
0
-0.5
P < 0.01
∆Τ(o C
)
Stefanadis C et al, JACC 2001 April
Therapeutic implication of Therapeutic implication of detection of vulnerable plaque detection of vulnerable plaque
StatinsStatins and Temperature post and Temperature post AMIAMI
1.6
1.2
1.4
0.2
.4
.6
.8
1
MIMI SASA
ToutouzasToutouzas et al. Am Heart L 2004et al. Am Heart L 2004
Effect of Atorvastatin on Plaque TemperatureN=256 pts
Stefanadis et al, submitted
0
.2
.4
.6
.8D
T
A C S , 0 A C S , 1 S A , 0 S A , 1
DT
(°C
)
ACS SA
No StatinsStatins
What influences local thermal heterogeneity of atheromatic lesions?
< 0,0010,02-0,13Clinical Syndrome< 0,0010,02-0,13Atorvastatin
P-valueSEMb- coefficient
Multivariate Analysis
Stefanadis et al, submitted
Prospective clinical study in 256 pts (136 under statins)
Red Light Catheter
•• The possible mechanism includes increased NO synthesis The possible mechanism includes increased NO synthesis •• Several previous studies have demonstrated light induced Several previous studies have demonstrated light induced vasorelaxationvasorelaxation in vivo in vivo and in vitroand in vitro
Kipshidze et al. J Am Coll Cardiol. 1998
Red Light Catheter and Vulnerable Plaque
0
0.04
0.08
0.12
0.16
Before Red Light
DT (OC) N=2
We applied red light in 3 intermediate lesions. Temperature was immediately decreased.
Kipshidze N, Toutouzas K, Stefanadis C
Red Light Laser Case
Thermography ProximalThermography Lesion 37,8
37,85
37,9
37,95
38
38,05
0.17oC
IVUS Catheter IVUS distalIVUS lesionIVUS proximalRed Light Balloon Catheter 37,64
37,66
37,68
37,7
37,72
37,74
37,76
37,78
37,8
0.08OC
Stent deployment Angiographic ResultFinal
Coronary ThermographyLimitation
• Effect of Flow
The “Cooling Effect of Blood Flow”
GW
D-GW
Th
Bl
Stefanadis C, et al. J Am Coll Cardiol 2003; Febr.
With flow
Without flow
With flow
Effect of Flow on ThermographyEffect of Flow on ThermographyThermocoreThermocore SystemSystem
VerheyeVerheye S, S, …… SerruysSerruys P. P. EurEur Heart J 2004;Jan:158Heart J 2004;Jan:158--6565
Thermography in vivo -Volcano
Without Flow
+ 0.+ 0.0707°°CC + 0.+ 0.1515°°CC
With flowDudek et al. TCT 2004
Coronary Thermography
Weiltz, …, Fitzgerald. Cathet Cardiovasc Interv 2004;27:256-61
Heat is transmitted in the direction of coronary flow
In vitro model for studying the effect of Flow on heat
Balloon-Occluded Thermography Catheter
Low pressure balloon Thermistor
One thermistorImpairment of flowMeasurements in non-significant lesions
Stefanadis et al. Cathet and Cardiovasc Interv 2003;March
Coronary Thermography
• Effect of Flow in Vivo
In Vivo Thermography
Th CB
Belardi J and O’Neil W, TCT 2004
O.3O.3--2.22.2ooCC
In Vivo ThermographyIn Vivo Thermography
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
Medispes Thermocore Volcano Imetrx Balloon-Cathet
Future Protocols for Detection of Thermal Energy
By measurement of thermal energy in a diseased ‘segment’:
• Accurate information regarding ‘regional’ vulnerability
• Elimination of ‘cooling effect’• Estimation of ‘vulnerable arteries’
rather than local plaque temperature
Plaque Thermography
• Coronary artery
• Coronary sinus
0
.1
.2
.3
.4
Tem
pera
ture
Diff
eren
ce (o
C)
0 2 3Control RCA LCA
0.09±0.07oC
0.15±0.08
0.27±0.10
Stefanadis et al, Am J Cardiol 2004 Jan
Coronary Sinus TemperatureCoronary Sinus Temperature
C
0
.1
.2
.3
.4
.5
.6
.7
∆T
(o
C)
0 20 40 60 80 100
CRP (mg/dl)
Coronary Sinus – Inflammation - Prognosis
Stefanadis et al, Am J Cardiol 2004;Jan
0
.2
.4
.6
.8
1
Cum
. Sur
viva
l
0 2 4 6 8 10 12 14Time
∆T < 0.25oC
∆T ≥ 0.25oC
Prospective Prospective MulticenterMulticenterStudies with ThermographyStudies with Thermography
Current Multicenter Studies for Evaluation of Vulnerable PLaques
• Parachute
• IBIS
• PROSPECT
• THERMO CAD
PARACHUTE TRIAL
IBIS TRIAL• Thorax Center, Rotterdam• 90 patients• Evaluation of intermediate lesions by:• Angiography• IVUS• Elastography• Virtual histology• OCT• Thermography
ClinicalClinicalAge and genderAge and gender
DiabetesDiabetes(+Metabolic (+Metabolic syndsynd))
CrClCrClACS acuityACS acuity
PROSPECT: Analysis domainsQCAQCA
SeveritySeverityEccentricityEccentricityIrregularityIrregularity
BurdenBurden
IVUSIVUSMorphologyMorphology
Severity Severity (CSN, PA)(CSN, PA)RemodelingRemodeling
BurdenBurden
VirtualVirtualHistologyHistology
CompositionCompositionAxial and muralAxial and mural
distributiondistributionBurdenBurden
ThermographyThermographyMax tMax tempemp
N, length andN, length andcircumferencecircumferenceof hot spotsof hot spots
Thermal burdenThermal burden
PalpographyPalpographyStress/strainStress/strainrelationshipsrelationships
Focal orFocal ordiffusediffuse
BiomarkersBiomarkersNecrosisNecrosis
InflammationInflammationThrombosisThrombosis
RuptureRuptureHemostasisHemostasis
HemodynamicsHemodynamics
Thermo CAD Study
• Thermography in two vessels (culprit and non-culprit)• Multicenter study• Preliminary results in 92 lesions and 46 patients from:
Hippokration Hospital, AthensOnnaseion Hospital, PiraeusPatra University Hospital, Patra
Thermo CAD study: Preliminary Results
Stefanadis, TCT 2004
In patients with ACS culprit and non-culprit lesions have increased thermal heterogeneity compared to patients with CSA
Widespread thermal heterogeneity
Stefanadis , TCT 2004
Thermo CAD study: Preliminary Results
0
.1
.2
.3C
olu
mn
1
A C S S A
DT
(°C
)
ACS SA
P = 0.001
Widespread thermal heterogeneity
In patients with ACS and CSA culprit and non-culprit lesions have similar thermal heterogeneity.
Stefanadis, TCT 2004
0
.1
.2
.3
.4
Culprit Non-culprit
ACS ACS
CSA CSA∆T
(OC
)N = 92 lesions46 patients
Thermo CAD study: Preliminary Results
Temperature and Coronary Artery Disease
1995-6
Ex vivo
1997-9
In vivo
2000-2
First clinical studies
• Correlation with morphology• Prognosis• Treatment
2003-
Cooling Effect of flow
New Technologies
Pathophysiology
Clinical Use?Clinical Use?
Conclusions
• Coronary thermography reflects the inflammatory activation in
atherosclerotic plaques. Neovascularization may play an
additive role.
• Coronary thermography provides significant clinical
information, but still the limitations need to be obviated.
• Coronary sinus temperature measurement may provide
information regarding the vulnerable patient.
• The ideal scenario would be the combination of thermography
and imaging techniques for the identification of the vulnerable
plaque.