PRIMARY Results of ADVISE ADenosine Vasodilation Independent Stenosis Evaluation Dr Justin Davies MD, PhD Imperial College London on behalf of the ADVISE

PRIMARY Results of ADVISE

ADenosine Vasodilation Independent Stenosis Evaluation

Dr Justin Davies MD, PhD

Imperial College London

on behalf of the ADVISE investigators

Disclosure Statement of Financial Interest

• Research Support/ Intellectual Property Rights

• Consulting Fees/Honoraria

• Volcano Corporation

• Medtronic, Volcano Corporation

Within the past 12 months, I or my spouse/partner have had a financial Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

FFR is established in clinical practice

At best it is only used in 6% of PCI in USA1

One barrier is the current requirement for vasodilator drugs such as adenosine

Contraindicated or disliked by patients

Adds to procedural time

Adds to procedural costs

1 Kleiman NS. J Am Coll Cardiol 2011; 58:1291-21

When coronary resistance is stable – pressure can be used as as a surrogate for flow to assess a coronary stenosis

0

0.2

0.4

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0 5 100

750

Vel

ocity

(M

-2)

Pre

ssur

e(m

mH

g)R

esis

tanc

e(m

mH

g M

-2)

Time (s)

150

75

Time (s)

2 4

Resistance (mm Hg s/m)

Pressure(mm Hg)

Velocity (m/s)

If we can identify a period of naturally occurring stable resistance

Why do we give drugs such as adenosine to

calculate fractional flow reserve (FFR)?

Pa

Pd

De Bruyne et al.JACC Vol. 22, No.1 July 1993:119-26

Marked damping of coronary pressure – necessitated the use of mean pressure in the development of FFR

Pa

Pd

Marked damping of coronary pressure – necessitated the use of mean pressure in the development of FFR

De Bruyne et al.JACC Vol. 22, No.1 July 1993:119-26

Phasic resistance during the cardiac cycle

ADVISE study

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Time (s)

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75

Resi

stan

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(mm

Hg

s/m

)Pr

essu

re(m

m H

g)Ve

loci

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/s)

Time (s)

2 4

ADVISE study

Phasic resistance during the cardiac cycle

0

0.2

0.4

0

1

2

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0 5 100

750

Vel

ocity

(M

-2)

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ssur

e(m

mH

g)R

esis

tanc

e(m

mH

g M

-2)

Time (s)

150

75

Resi

stan

ce

(mm

Hg

s/m

)Pr

essu

re(m

m H

g)Ve

loci

ty (m

/s)

Time (s)

2 4

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0.2

0.4

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0 5 100

750

Vel

ocity

(M

-2)

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ssur

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mH

g)R

esis

tanc

e(m

mH

g M

-2)

Time (s)

150

75

Resi

stan

ce

(mm

Hg

s/m

)Pr

essu

re(m

m H

g)Ve

loci

ty (m

/s)

Time (s)

2 4

Fully automated algorithms

Identification of naturally low resistance period

Uses pressure only

Wav

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Sen S, Escaned J, Davies JE et al. JACC (in press 2011)Davies JE et al. Circulation 2006;113:1767-1778Davies JE et al. Circulation 2011;124:1565-1572

Identification of wave-free period

Hypothesis 1

Resistance measured at rest during the resting wave-free period is similar to mean resistance during hyperaemia.

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ocity

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)Pr

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mH

g)R

esis

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e(m

mH

g M

-2)

Time (s)

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0.2

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ocity

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e(m

mH

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Time (s)

Hyperaemic mean resistance Resting wave-free resistance

ADVISE study

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0 100 200 300 400 500 600 700 800 900

70

120

Pre

ssur

e (m

m H

g)

Time (ms)

Hypothesis 2

The Pd/Pa ratio (iFR) during the resting wave-free period was similar to FFR.

ADVISE study

Resting wave-free resistance vs. mean hyperaemic resistance

n=39

Intra-coronarypressure and flow velocity

measurements

Baseline resistance assessment

Resistance assessment under pharmacological

vasodilatation

iFR vs. FFRn=157

Intra-coronarypressure measurements

iFR & FFR assessment

ADVISE StudyADenosine Vasodilation Independent Stenosis Evaluation

Part 1Proof of concept

Part 2Validation study

ADVISE study demographics

n=156 lesionsage = 63 years

RISK FACTORS

VESSEL CHARACTERISTICS

ADVISE study

Test stability and magnitude of resistance during wave-free period in comparison to during adenosine hyperaemia

Hypothesis 1

Resting wave-free resistance

Hyperaemic mean

resistance

Stability of resistance is similar over the wave-free period and during hyperaemia

Coeffi

cien

t of V

aria

tion

of re

sist

ance

Sen S, Escaned J, Davies JE et al. JACC (in press 2011)ADVISE study


Hyperaemic mean

resistance

p=0.96

Stability of resistance is similar over the wave-free period and during hyperaemia

Coeffi

cien

t of V

aria

tion

of re

sist

ance


Resting mean

resistance

Resi

stan

ce

(mm

Hg

s/m

)

Magnitude of resistance is similar over the wave-free period and during hyperaemia

0

800


Hyperaemicmean

resistanceADVISE study


Hyperaemicmean

resistance

Resting mean

resistance

Resi

stan

ce

(mm

Hg

s/m

)

p<0.001

p<0.001

p=0.70

Magnitude of resistance is similar over the wave-free period and during hyperaemia

0

800

ADVISE study

Resistance measured at rest during the wave-free period…

Hypothesis 1

Resistance measured at rest during the wave-free period…

is similar in both stability and magnitude

to values achieved under adenosine hyperaemia.

Hypothesis 1

Assess whether iFR was numerically similar to Fractional flow reserve.

Hypothesis 2

Definition: Instantaneous pressure gradient, across a stenosis during the wave-free period, when resistance is constant and minimised in the cardiac cycle

iFR = instantaneous wave-free ratio

Pa

Pd

0 100 200 300 400 500 600 700 800 900

70

120

Pre

ssur

e (m

m H

g)

Time (ms)

Wave-free period

Close relationship between iFR and FFR

y=1.022x + 0.03Regression coefficient

FFR

iFR



r = 0.90


FFR

iFR




Left coronary artery

Right coronary artery

FFR

iFR

r = 0.90


Magnitude of hyperaemia does not explain the small difference between iFR and FFR

Δ Abs Hyperaemic – wave-free resistance (mmHg s/m)

ΔFFR

- iF

R

ADVISE study

Diagnostic efficiency of iFR

Sen S, Escaned J, Davies JE et al. JACC (in press 2011)

iFR positive

iFRnegative

FF

R

False (+)

False (-)

Assessment of diagnostic efficiency of iFR



Diagnostic accuracy

(+) predictive value

(-) predictive value

Sensitivity

Specificity

88%

91%

85%

85%

91%


FF

R

False (+)

False (-)

95% CI variability in FFR*



Assessment of diagnostic efficiency of iFR after adjustment for inherent variability in FFR

*De Bruyne B et al. Circulation. 1996;94:1842-1849 Circulation 2006;114;1321-1341

iFR positive

iFRnegative

Diagnostic accuracy

(+) predictive value

(-) predictive value

Sensitivity

Specificity

95%

97%

93%

93%

97%

88%

91%

85%

85%

91%

Adjusting for variability in FFR

ADVISE study

Summary

Identified a wave-free period in cardiac cycle when resistance is naturally stabilized and minimal avoiding the need for administration of adenosine

Wav

e-fr

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Summary

iFR measured during this wave-free period gives a measure of stenosis severity similar to FFR

Clinical implications of iFR

Removes barriers to adoption of physiological assessment

Increased applicability

Improved work-flow in catheter lab

Improves patient experience

ADVISE teamHospital Clínico San Carlos Javier Escaned, Rafael Mila

Royal Brompton HospitalCarlo Di Mario

Imperial CollegeSayan Sen

Iqbal Malik, Jamil Mayet, Alun Hughes, Darrel Francis, Ghada W Mikhail, Rodney A Foale, Jason Tarkin, Ricardo Petraco, Christopher Broyd, Richard Jabbour, Amarjit Sethi, Christopher Baker, Michael Bellamy, Mahmud Al-Bustami, David Hackett, Masood Khan, David Lefroy, and Kim H Parker.

ADVISE team

Wav

e-fr

ee p

erio

dW

ave-

free

per

iodHospital Clínico San Carlos

Javier Escaned, Rafael Mila

Royal Brompton HospitalCarlo Di Mario

Imperial CollegeSayan Sen

Iqbal Malik, Jamil Mayet, Alun Hughes, Darrel Francis, Ghada W Mikhail, Rodney A Foale, Jason Tarkin, Ricardo Petraco, Christopher Broyd, Richard Jabbour, Amarjit Sethi, Christopher S Baker, Micheal Bellamy, Mahmud Al-Bustami, David Hackett, Masood Khan, David Lefroy, and Kim H Parker. advisestudy.org

[email protected]

Documents

PRIMARY Results of ADVISE ADenosine Vasodilation Independent Stenosis Evaluation Dr Justin Davies MD, PhD Imperial College London on behalf of the ADVISE