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PRIMARY Results of ADVISE
ADenosine Vasodilation Independent Stenosis Evaluation
Dr Justin Davies MD, PhD
Imperial College London
on behalf of the ADVISE investigators
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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
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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
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When coronary resistance is stable – pressure can be used as as a surrogate for flow to assess a coronary stenosis
0
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Time (s)
150
75
Time (s)
2 4
Resistance (mm Hg s/m)
Pressure(mm Hg)
Velocity (m/s)
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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)?
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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
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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
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Phasic resistance during the cardiac cycle
ADVISE study
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ADVISE study
Phasic resistance during the cardiac cycle
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Hg
s/m
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loci
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Fully automated algorithms
Identification of naturally low resistance period
Uses pressure only
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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
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Hypothesis 1
Resistance measured at rest during the resting wave-free period is similar to mean resistance during hyperaemia.
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Hyperaemic mean resistance Resting wave-free resistance
ADVISE study
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Hypothesis 2
The Pd/Pa ratio (iFR) during the resting wave-free period was similar to FFR.
ADVISE study
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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
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ADVISE study demographics
n=156 lesionsage = 63 years
RISK FACTORS
VESSEL CHARACTERISTICS
ADVISE study
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Test stability and magnitude of resistance during wave-free period in comparison to during adenosine hyperaemia
Hypothesis 1
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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
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Resting wave-free resistance
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
Sen S, Escaned J, Davies JE et al. JACC (in press 2011)ADVISE study
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Resting mean
resistance
Resi
stan
ce
(mm
Hg
s/m
)
Magnitude of resistance is similar over the wave-free period and during hyperaemia
0
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Resting wave-free resistance
Hyperaemicmean
resistanceADVISE study
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Resting wave-free resistance
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
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Resistance measured at rest during the wave-free period…
Hypothesis 1
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Resistance measured at rest during the wave-free period…
is similar in both stability and magnitude
to values achieved under adenosine hyperaemia.
Hypothesis 1
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Assess whether iFR was numerically similar to Fractional flow reserve.
Hypothesis 2
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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
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Close relationship between iFR and FFR
y=1.022x + 0.03Regression coefficient
FFR
iFR
Sen S, Escaned J, Davies JE et al. JACC (in press 2011)ADVISE study
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Close relationship between iFR and FFR
r = 0.90
y=1.022x + 0.03Regression coefficient
FFR
iFR
Sen S, Escaned J, Davies JE et al. JACC (in press 2011)ADVISE study
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Close relationship between iFR and FFR
y=1.022x + 0.03Regression coefficient
Left coronary artery
Right coronary artery
FFR
iFR
r = 0.90
Sen S, Escaned J, Davies JE et al. JACC (in press 2011)ADVISE study
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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
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ADVISE study
Diagnostic efficiency of iFR
Sen S, Escaned J, Davies JE et al. JACC (in press 2011)
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iFR positive
iFRnegative
FF
R
False (+)
False (-)
Assessment of diagnostic efficiency of iFR
Left coronary artery
Right coronary artery
Diagnostic accuracy
(+) predictive value
(-) predictive value
Sensitivity
Specificity
88%
91%
85%
85%
91%
Sen S, Escaned J, Davies JE et al. JACC (in press 2011)ADVISE study
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FF
R
False (+)
False (-)
95% CI variability in FFR*
Left coronary artery
Right coronary artery
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
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Summary
Identified a wave-free period in cardiac cycle when resistance is naturally stabilized and minimal avoiding the need for administration of adenosine
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Summary
iFR measured during this wave-free period gives a measure of stenosis severity similar to FFR
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Clinical implications of iFR
Removes barriers to adoption of physiological assessment
Increased applicability
Improved work-flow in catheter lab
Improves patient experience
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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.
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ADVISE team
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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