Digital reactive hyperemia

(Endo-PAT 2000), a novel

diagnostic test for the

assessment of endothelial

function

Sungha Park

Endothelium as a CVD risk

factors transducerTraditional Risk Factors

Endothelial Dysfunction:

“The Risk of the Risk Factors”

Non-Traditional

Risk Factors

Local Factors

(Shear)

Genetic

Predisposition

Unknown

Factors

Vascular

RemodellingInflammation

Vascular

ContractionThrombosis

Plaque

Rupture

Bonetti et al.

ATVB 2003; 23:168

Four questions about

endothelial function

• Can we measure it specifically and accurately

• Is it associated with CVD risk factors

• Is it associated with CVD

Quantitative coronary angiography

Venous Occlusion Plethysmography

Brachial Flow Mediated Dilation

Endo PAT system overview

Peripheral arterial tone

Endo PAT probe

Pressure-Volume Compliance Curve

Example of finger PWA recording

Kuvin JT et al. Am Heart J 2003;146:168-174

Examination Protocol

• Study performed in a thermoneutral environment

• Overnight fasting

• Refrain from smoking, alcohol and caffeine on the

day of the examination

PAT reactive hyperemia protocol

Endo PAT demonstration

PAT ratio

Correcting for baseline diameterPAT Response Vs. Baseline Amplitude

N=310

10 point

average

Systemic correction

PAT measurement

Results

Endo-PAT 2000 Advantages

• Non-invasive

• Easy to use, non user-dependent

• Automatic analysis

• Supports both clinical and research applications

• Reliable and reproducible

• FDA cleared and CE marked & CSA certified

Advantages of Endo-PAT2000 Vs. FMD

• Controls for systemic effects

• Normalizes for baseline amplitude

• Non user-dependent – technician operated &

automated analysis

• Data archiving supports research applications

• Occlusion quality assessment

• Better reproducibility

CASE 1

M/ 53

HTN (+), DM (-), Smoking (-)

Endo-PAT index 2.364

FMD % Diameter-RH 7.3

% Diameter-NTG 12.2

CASE 1 FMD

Baseline

Reactive hyperemia NTG

0.410 cm

0.440 cm : 7.3 % ↑ 0.460 cm : 12.2 % ↑

CASE 1 Endo-PAT

CASE 2

M/ 44

HTN (+), DM (-), Smoking (+)

Endo-PAT index 2.00

FMD % Diameter-RH 4.1

% Diameter-NTG 4.1

CASE 2 FMD

Baseline

Reactive hyperemia NTG

0.393 cm

0.409 cm : 4.1 % ↑ 0.409 cm : 4.1 % ↑

CASE 2 Endo-PAT

Role of NO in Reactive Hyperemia

• Performed by Prof. Gerhard-Herman et al.,

Harvard Med School

• A prospective study of Reactive Hyperemia

mechanism

• 21 normal patients before and after L-NAME

(eNOS inhibitor)

• 20 control patients before and after saline

• PAT was used to measure endothelial response

Harvard Study - Results

•Average reduction in response to L-NAME =61%

The Effect of Nitric Oxide Inhibition on PWA Following Release of Occlusion

0

20

40

60

80

100

120

140

160

180

1 2 3 4 5

Contro l

L -NAM EIncrease in Pulse-Wave Amplitude (%)

Case examples

Gerhard-Herman M et al. Circulation 2002;102:Suppl II:851

PAT Vs. FMD

Courtesy of Dr. Kuvin,

New-England Medical

Center

N=89

Kuvin JT et al. Am Heart J 2003;146:168-174

PAT Vs. FMD

p

Four questions about

endothelial function

• Can we measure it specifically and accurately

• Is it associated with CVD risk factors

• Is it associated with CVD

PAT hyperemia and CV risk factors

Kuvin JT et al. Am Heart J 2003;146:168-174

Number of cardiac risk factors

0 3 6

R=0.3, P=0.02

CHD risk vs. Endo-PAT index

0.0

1.0

2.0

3.0

4.0

5.0

1.01.52.02.53.03.5

0.0

1.0

2.0

3.0

4.0

5.0

0.20.40.60.81.01.2

Endo-PAT index Log Endo-PAT index

Relative risk

R = 0.375 , P = 0.003 R = 0.361 , P = 0.004

YUMC data 2005

Four questions about endothelial function

• Can we measure it specifically and accurately

• Is it associated with CVD risk factors

• Is it associated with CVD

PAT Hyperemic Response – Mayo StudyCompared to Coronary Response to Acetylcholine

Abnormal

Endothelial

Function

Baseline Acetylcholine

Normal

Endothelial

Function

Bonetti PO et al. J Am Coll Cardiol 2004;44:2137-2141

PAT

PAT Hyperemic Response Compared to Coronary Response to Acetylcholine

(Abnormal if CBF

PAT hyperemia and CAD

P=0.004

n=35 n=33

(Exercise Myocardial

Perfusion Imaging)

Kuvin JT et al. Am Heart J 2003;146:168-174

Conclusion

• Reactive hyperemia PWA is a novel method to

measure endothelial function

• It is easy to use and relatively objective

• The gold standard is still FMD: More clinical

experience is needed with regards to clinical

studies