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Coronary Artery Thermography - summitMD.com

Coronary Artery Thermography

The 10th Anniversary, Interventional Vascular

Therapeutics Angioplasty Summit

2005 TCT Asia Pacific

Christodoulos Stefanadis

Professor of Cardiology

Athens Medical School


In the search for vulnerable plaque

What???

•Thin cap

•Lipid core

•Positive remodeling

•Reduction of smooth muscle cells

Santorini Congress Conclusions

•Macrophages

Eur Heart J 2004;25(12):1077-1082


Inflammation – Atheromatosis


Can we detect the vulnerable plaque?

NO IDEAL METHOD

Technique Fibrous cap Lipid core Inflammation Calcium Thrombus VV

IVUS + ++ - +++ + -

Angioscopy + ++ - - +++ -

OCT +++ +++ + +++ + -

MRI + ++ + ++ + -

IVUS+contrast + ++ + ++ + ++?

Thermography - - +++ - - -


Thermography

The Fire Within


Thermal Heterogeneity in

Atherosclerotic Plaques

Medispes System

Thermocore System

Casscells et al, Lancet 1996

Volcano System

RADI System


Plaque Thermography

• What do we measure?


Thermal Heterogeneity –Inflammatory

In vivo experimental study

Control

1.2 o C

Atheromatous

Ex vivo measurements

Verheye et al, Circulation 2002;105(13):1596-601


Correlation of Histology – Temperature

Ex Vivo in Carotid Plaques

In 27 patients with carotid stenosis: In endarterectomy

specimens histology was correlated with temperature

measurements

Madjid M, Naghavi M, et al. Am J Cardiol 2002;90:36-39


Correlation of human coronary plaque

temperature measurements with the presence of

inflammatory markers in pathology examination

+ 0.01

01°C

0% concentration of macrophage marker CD-68

Milan-Athens Experience


Correlation of human coronary plaque

temperature measurements with the presence of

inflammatory markers in pathology examination

Patient With Thermal Heterogeneity (TD: 0.08 o C)

+ 0.08

08°C

20% concentration of macrophage marker CD-68

Milan-Athens Experience


Correlation of human coronary plaque

temperature measurements with systemic

inflammatory markers

1

.8

∆T ( O C)

.6

.4

.2

0

0 10 20 30

CRP (mg/dl)

Stefanadis et al. J Mol Cell Cardiol 2000


Vasa Vasorum

Angiogenesis in vasa vasorum

Control 2 weeks hyperlipidemic diet 6 weeks

No endothelial dysfunction Endothelial dysfunction

Vasa vasorum development is observed prior to

endothelial dysfunction

Herrmann et al. Cardiovasc Res 2001;51:762-6


Experimental Protocol

Effect of Vasa Vasorum on Plaque Temperature

39

38,8

Temperature ( o C)

38,6

38,4

38,2

38

37,8

37,6

Without VV

VV

Athens Medical School


Plaque Thermography

• What do we measure?

• Inflammation

• Neovascularization


Thermography

Coronary Artery

Coronary Sinus


Clinical Studies

Thermal Heterogeneity and

Diabetes Mellitus Type 2

An Increased Inflammatory

Activation?


Diabetes Mellitus and

Temperature Measurements

0,2

P = 0.01

∆T ( O C)

0,15

0,1

0,05

0

DM

non-DM

Toutouzas K, et al. Diabetes Care in press


Diabetes Mellitus and Temperature

Measurements

P = 0.02 P = 0.67

Diabetic patients with ACS have higher thermal heterogeneity

compared to non diabetic patients

Toutouzas K, et al. Diabetes Care in press


Prolonged Thermal

Heterogeneity Post ACS

A Prolonged Inflammatory

Activation?


Prolonged inflammation

Prolonged thermal heterogeneity

post MI

DT

Units

( o C)

.9

.8

.7

.6

.5

.4

.3

.2

.1

0

MI > 2 months Stable Angina

DT

N=56

AMI

SA

Toutouzas K et al, Am Heart J 2004


Prognostic implication of

detection of vulnerable plaque


Stenting in ‘Hot’ Plaques

=

Cold plaque

Hot plaque


Temperature and Prognosis post PCI

FV

2.0

P < 0.01

∆Τ ( o C)

1.5

1.0

0.5

0

-0.5

No Event

Event

Stefanadis C et al, JACC 2001 April


Therapeutic implication of

detection of vulnerable plaque


Statins and Temperature post

1.6

1.4

1.2

1

.8

.6

.4

AMI

.2

0

MI

SA

Toutouzas et al. Am Heart L 2004


DT

ACS, 0 ACS, 1 SA, 0 SA, 1

Effect of Atorvastatin on Plaque

N=256 pts

Temperature

.8

No Statins

Statins

DT (°C)

.6

.4

.2

0

ACS

SA

Stefanadis et al, submitted


What influences local thermal

heterogeneity of atheromatic lesions?

Prospective clinical study in 256 pts (136 under statins)

Multivariate Analysis

b- coefficient

SEM

P-value

Atorvastatin

-0,13

0,02

< 0,001

Clinical Syndrome

-0,13

0,02

< 0,001

Stefanadis et al, submitted


Red Light Catheter

• The possible mechanism includes increased NO synthesis

• Several previous studies have demonstrated light induced vasorelaxation in vivo

and in vitro

Kipshidze et al. J Am Coll Cardiol. 1998


Red Light Catheter and

Vulnerable Plaque

0.16

DT ( O C) N=2

0.12

0.08

0.04

0

Before

Red Light

We applied red light in 3 intermediate lesions. Temperature was immediately decreased.

Kipshidze N, Toutouzas K, Stefanadis C


Red Light Laser Case

Final

38,05 37,8

37,78

38

37,76

37,74

37,95

37,72

37,9

37,7

37,68

37,85

37,66

0.17 o C

0.08 O C

Thermography Stent Red IVUS Light deployment

Catheter Balloon Lesion Proximal Catheter

37,8 37,64

IVUS Angiographic

proximal distal lesion

Result


Coronary Thermography

Limitation

• Effect of Flow


The “Cooling Effect of Blood

Flow”

Bl

GW

Th

D-GW

Without flow

With flow With flow

Stefanadis C, et al. J Am Coll Cardiol 2003; Febr.


Effect of Flow on Thermography

Thermocore System

Verheye S, … Serruys P. Eur Heart J 2004;Jan:158-65


Thermography in vivo -

Volcano

+ 0.07

07°C

+ 0.15

15°C

With flow

Without Flow

Dudek et al. TCT 2004


Coronary Thermography

In vitro model for studying the effect of Flow on heat

Heat is transmitted in the direction of coronary flow

Weiltz, …, Fitzgerald. Cathet Cardiovasc Interv 2004;27:256-61


Balloon-Occluded Thermography

Catheter

Low pressure

balloon

One thermistor

Impairment of flow

Measurements in non-significant lesions

Thermistor

Stefanadis et al. Cathet and Cardiovasc Interv 2003;March


Coronary Thermography

• Effect of Flow in Vivo


In Vivo Thermography

O.3-2.2

o C

B

Th

C

Belardi J and O’Neil W, TCT 2004


In Vivo Thermography

0,8

0,7

0,6

0,5

0,4

0,3

0,2

0,1

0

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


Coronary Sinus Temperature

C

.4

0.27±0.10

Temperature Difference (oC)

.3

.2

.1

0

0.09±0.07 o C

0.15±0.08

0 2 3

Control RCA LCA

Stefanadis et al, Am J Cardiol 2004 Jan


Coronary Sinus – Inflammation - Prognosis

∆ T (oC)

.7

.6

.5

.4

.3

.2

.1

0

0 20 40 60 80 100

CRP (mg/dl)

Cum. Survival

1

.8

.6

.4

.2

0

∆T < 0.25 o C

∆T ≥ 0.25 o C

0 2 4 6 8 10 12 14

Time

Stefanadis et al, Am J Cardiol 2004;Jan


Prospective Multicenter

Studies with Thermography


Current Multicenter Studies for

Evaluation of Vulnerable PLaques

• Parachute

• IBIS

• PROSPECT

• THERMO CAD


PARACHUTE TRIAL


IBIS TRIAL

• Thorax Center, Rotterdam

• 90patients

• Evaluation of intermediate lesions by:

• Angiography

• IVUS

• Elastography

• Virtual histology

• OCT

Thermography


PROSPECT: Analysis domains

Clinical

Age and gender

Diabetes

(+Metabolic synd)

CrCl

ACS acuity

Virtual

Histology

Composition

Axial and mural

distribution

Burden

QCA

Severity

Eccentricity

Biomarkers

Irregularity

Burden

Necrosis

Inflammation

Thrombosis

Rupture

Hemostasis

Hemodynamics

Palpography

Stress/strain

relationships

Focal or

diffuse

IVUS

Morphology

Severity

Remodeling

Burden

Severity (CSN, PA)

Thermography

Max tempt

N, length and

circumference

of hot spots

Thermal burden


Thermo CAD study: Preliminary Results

Thermo CAD Study

Thermography in two vessels (culprit

and non-culprit)

• Multicenter study

• Preliminary results in 92 lesions and 46

patients from:

‣Hippokration Hospital, Athens

‣Onnaseion Hospital, Piraeus

‣Patra University Hospital, Patra

Stefanadis, TCT 2004


ACS

SA

Thermo CAD study: Preliminary Results

Widespread thermal heterogeneity

.3

P = 0.001

DT (°C)

Co lu m n 1

.2

.1

0

ACS

SA

In patients with ACS culprit and non-culprit lesions have increased

thermal heterogeneity compared to patients with CSA

Stefanadis , TCT 2004


Thermo CAD study: Preliminary Results

Widespread thermal heterogeneity

.4

N = 92 lesions

46 patients

∆T ( O C)

.3

.2

ACS

CSA

ACS

CSA

.1

0

Culprit

Non-culprit

In patients with ACS and CSA culprit and non-culprit lesions have

similar thermal heterogeneity.

Stefanadis, TCT 2004


Temperature and Coronary

Artery Disease

1995-6

1997-9

2000-2

2003-

Ex vivo

In vivo

First clinical studies

• Correlation with morphology

• Prognosis

• Treatment

Cooling Effect of flow

Pathophysiology

New Technologies

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.

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