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.