Instantaneous wave
Instantaneous
wave‐Free
Free Ratio Ratio
(iFR)
Reserva Instantanea de Fluxo
Ricardo Petraco
BHF Clinical Research Fellow
Specialist Registrar in Cardiology
International Centre for Circulatory Health
International
Centre for Circulatory Health
National Heart and Lung Institute
Imperial College London
Imperial College London
Instantaneous wave‐Free Ratio (iFR)
B
Beneficios
fi i da revascularizacao
d
l i
guiada
i d por fisiologia
fi i l i
FAME II
Instantaneous wave‐Free Ratio (iFR)
Beneficios da revascularizacao guiada por fisiologia
Uso da Reserva Fracionada de Fluxo (FFR) ja incorporado
nos Guidelines...
Instantaneous wave‐Free Ratio (iFR)
FFR, porque tao pouco utilizada?
'As for its everyday role in cath labs, FFR use during PCI varies dramatically from country to country as low as 5% to 8%
dramatically from country to country... as low as 5% to 8% worldwide.” Bernard de Bruyne, interview to Heartwire.com
US: 6%, ,
Europe: 10%
Brasil: ?? (
Brasil
: ?? (menos
menos que 5%)
Instantaneous wave‐Free Ratio (iFR)
FFR porque tao pouco utilizada?
FFR, porque
Culpa parcial da Adenosina...
Custos: US: US$ 150/vial $
/
Contra‐indicacoes: Asma, bloqueio cardiaco
Efeitos colaterais: Hipotensao, dor toracica, flushing Instantaneous wave‐Free Ratio (iFR)
FFR porque tao pouco utilizada?
FFR, porque
Culpa parcial da Adenosina...
Custos: US: US$ 150/vial $
/
Contra‐indicacoes: Asma, bloqueio cardiaco
Efeitos colaterais: Hipotensao, dor toracica, flushing Logistica: g
• IC x IV? • Acesso venoso central?
• Dose (140‐200mcg/Kg/min)? • Definicao de “hiperemia estavel”?
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
de Fluxo
Busca pela maior adocao da revascularizacao guiada por fisiologia no laboratorio de hemodinamica,
no laboratorio de hemodinamica, atraves da simplificacao... Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
Bases fisiologicas
Bases fisiologicas
Bases Sen S, Escaned J, Davies JE et al. JACC (2012)
Instantaneous wave‐Free Ratio (iFR)
SSe fluxo
fl
coronariano
i
e o que importa, i
t
porque
p
q nao medimos fluxo?
Reproducibilidade da medicao de fluxo coronarinao
3.00
Reeserva de fluxo medidaa 2
2.50
Measurement Error = 25%!!
2.00
1.50
1.00
0.50
0.00
0.00
0.50
1.00
1.50
2.00
Reserva de fluxo medida 1
2.50
3.00
Instantaneous wave‐Free Ratio (iFR)
O uso da Pressao como substituto do Fluxo coronariano
Gradiente de
e pressao (mmHg)
Et
Estenose
Pressure = Flow x Resistance
∆P = K1v + K2v2
C
B
A
Fluxo coronariano (cm/s)
Instantaneous wave‐Free Ratio (iFR)
O uso da Pressao como substituto do Fluxo coronariano
Gradiente de
e pressao (mmHg)
Et
Estenose
∆P = K1v + K2v2
C
B
A
Fluxo coronariano (cm/s)
R i
Resistencia i
coronariana
distal
distal CONSTANTE
Instantaneous wave‐Free Ratio (iFR)
O uso da Pressao como substituto do Fluxo coronariano
Velocity
(m/
) /s)
(M -2
Veloccity
O ciclo
O ciclo cardiaco completo tem resistencia
tem resistencia variavel
Velocity
(m/s)
0.4
0.2
0
Pressure
Prressure
(m
mm Hg)
(m
mmHg)
3
Pressure
((mm Hg)
g)
1502
751
Resistancce Resistan
nce
-2
(mm Hg s/
/m)
(mmHg M )
0
750
Resistance (mm Hg s/m)
0
0
5
2
Time (s)
Time (s)
10
4
Instantaneous wave‐Free Ratio (iFR)
O uso da Pressao como substituto do Fluxo coronariano
Velocity
(m/
) /s)
(M -2
Veloccity
Mas existe um um periodo
periodo de de resistencia
resistencia estavel
estavel... ... Velocity
(m/s)
0.4
0.2
0
Pressure
Prressure
essure
(m
mm Hg)
mmHg)
(m
3
Pressure
(mm Hg)
(mm
Hg)
1502
751
Resistancce Resistan
nce
(mm Hg s/
/m)
(mmHg M -2)
0
750
Resistance (mm Hg s/m)
0
0
2
5
Time (s)
Time (s)
4
10
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) R
Reserva
I
Instantanea
d Fl
de Fluxo
Bases fisiologicas
Bases fisiologicas
Pressao e e fluxo
fluxo
andam juntos
Wave‐‐ffree period
Wave
p
Resistencia estavel
Resistencia estavel
e minimizada
e minimizada
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) R
Reserva
I
Instantanea
d Fl
de Fluxo
Bases fisiologicas
Bases fisiologicas
iFR – Ideia nova???
Pa
Pd
De Bruyne et al.
JACC Vol. 22, No.1 July 1993:119‐26
,
y
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) R
Reserva
I
Instantanea
d Fl
de Fluxo
Como e calculado
Como e calculado??
150
Pa and Pd Pressure (mmHg)
A
50
B
120
C
m Hg)
Pressure (mm
Wave‐free period
Pa
Pd
70
0
100
200
300
400
500
Time (ms)
600
700
800
900
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) R
Reserva
I
Instantanea
d Fl
de Fluxo
Como e calculado
Como e calculado??
150
Pa and Pd Pressure (mmHg)
A
Pd wave‐free period
iFR = Pa a
wave‐free period
f
i d
50
B
120
C
m Hg)
Pressure (mm
Wave‐free period
Pa
Pd
70
0
100
200
300
400
500
Time (ms)
600
700
800
900
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
Validacao inicial
ADVISE study
Sen S, Escaned J, Davies JE et al. JACC (2012)
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
Validacao inicial – ADVISE study
93%
Sen S, Escaned J, Davies JE et al. JACC (2012)
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
de Fluxo
p<0.001
800
Resistancce (
(mm Hg s/
/m)
p<0.001
p=0.70
0 70
0
Resting mean resistance
Hyperaemic
mean resistance
Resting wave‐free resistance
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
Validacao inicial – ADVISE study
Left coronary artery
False (+)
FFR
g
y
y
Right coronary artery
False (-)
iFR
positive
Diagnostic accuracy 88%
(+) predictive value
91%
()
(‐) predictive value di ti
l
85%
Sensitivity 85%
Specificity
Specificity 91%
iFR
negative
Sen S, Escaned J, Davies JE et al. JACC (2012)
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
Validacao inicial – ADVISE study
Frequeency (%)
25
ADVISE study
20
DEFER study
15
10
5
0
0 0.1
0.2
0.3
0.4
0.5
0.6
0.7
FFR ranges
FFR ranges
0.8
0.9
1
2
0.3
0.4
0.5
0.6
0.7
0.8
FFR ranges
FFR ranges
0.9
1
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
Qual a concordancia entre iFR e FFR na populacao de pacientes em que a FFR e utilizada
populacao de pacientes em que a FFR e utilizada, no dia a dia do cath lab?
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
2o passo – validacao clinica
ADVISE ‐ Registry
g y
Investigators Carlo Di Mario, Royal Brompton Hospital, London, UK
Javier Escaned, Clinico San Carlos, Madrid, Spain
Simon Redwood, St Thomas’s Hospital, London, UK
Justin Davies, Imperial College, London, UK
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Reserva Instantanea de Fluxo
ClinicalRegistry (N=339)
Clinical Registry
ADVISE –
ADVISE
RRegistry
i t (N 339)
Frequency (%)
25
FFR PET study
FFR‐PET study
20
15
10
5
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0.1
0.2
0.3
FFR reproducibility study
Frequen
ncy (%)
0.5
0.6
0.7
0.8
0.9
1
0.9
1
ADVISE trial
ADVISE study
ADVISE
study
DEFER study
DEFER study
25
0.4
20
15
10
5
0
0.1
0.2
0.3
0.4
0.5
0.6
FFR 0.7
0.8
0.9
1
0.1
0.2
0.3
0.4
0.5
0.6
0.7
FFR ranges
0.8
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) s a a eous a e ee a o ( )
Reserva Instantanea de Fluxo
2o p
passo – validacao clinica
ADVISE – Registry
1.0
1
0.9
0.9
iFFR (+) and FFR (+)
0.8
iFR
0.7
0.6
0.5
0.4
0.8
0.7
86%
0.6
0.5
0.4
03
0.3
0.2
0.1
0.3
0
0.2
0
0.2
0.3
0.4
0.5
0.6
FFR 0.7
0.8
0.9
1.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
iFR(+) and FFR (‐)
0.8
0.9
1
Diagnostic performance of a novel index, the instantaneous Di
ti
f
f
l i d th i t t
wave‐free ratio (iFR), for the detection of functionally significant coronary artery stenosis
significant coronary artery stenosis
Jin Joo Park1, Han‐Mo Yang1, Kyung Woo Park1, Hae‐Young Lee1, Chang
Chang‐Wook
Wook Nam2, Joon
Joon‐Hyung
Hyung Doh 3, Bon
Bon‐Kwon
Kwon Koo
Koo1, Justin E Davies4, Javier Escaned5, Hyo‐Soo Kim1
Cardiovascular Center, Seoul National University Hospital
1
Department
p
of Internal Medicine and Cardiovascular Center,, Seoul National Universityy Hospital,
p , Seoul,, Korea
Division of Cardiology, Keimyung University Dongsan Medical Center, Daegu, Korea
3 Division of Cardiology, Inje University Ilsan Paik Hospital, Korea
4 International Center for Circulatory Health, National heart and Lung Institute, Imperial College London, London, United Kingdom
5 Cardiovascular Institute, Hospital Clinico San Carlos, Madrid, Spain
2
Study procedure
iFR corelab
l b
FFR/imaging Core lab
anonymization & coding as ASCII text file
868 881 671 766 869 862 882 667 766 868
854 882 665 767 870 846 882 661 767 870
836 882 657 767 870 827 882 653 767 870
816 882 651 767 870 809 882 646 767 870
803 883 643 768 870 796 883 639 768 870
790 883 635 768 870 787 883 630 768 870
783 883 626 768 870 779 883 621 768 870
773 883 616 769 871 767 883 612 769 871
761 883 610 769 871 756 883 608 769 871
I . Background
II . Methods
III .Results IV .Summary
Se o iFR for calculado de Se o iFR for calculado
Se o iFR for de maneira correta
de maneira
correta…
…
Algorithm
Study
N
Blinded
Population
Cut‐point
AUROC
Classification agreement
("diagnostic accuracy")
FFR 0.8
iFR vs FFR
iFR vs FFR*
Author
Imperial/Volcano
157
no
Intermediate and
severe
0.83
0.93
94%
Sen et al.1
ADVISE ‐ Registry 339
no
Intermediate
0.89
0.86
94%
Petraco et al. 2
Korean
238
yes
Intermediate
0.9
0.89
94%
Park et al. 3
Summary
734
0.89
0.89
94%
VERIFY
206
0.83
0.87
71%
ADVISE
St Jude Medical
no
Intermediate and
severe
Berry et al. 4
* Adjusted for intrinsic variability of FFR
1.
2.
3.
Sen et al. J Am Coll Cardiol. 2012 Apr 10;59(15):1392‐402
Petraco et al. (EuroPCR 2012)
Park et al. (EuroPCR 2012). 4. Berry et al. (ACC 2012)
Area Under Curve
iFR 0.93
iFRa 0.94
FFR 0.96
CLARIFY an ADVISE sub‐study
p=0.48
n=51
SIGNIFIC
CANT STEN
NOSIS
Instantaneous wave‐Free Ratio (iFR) R
Reserva Instantanea de Fluxo
I
d Fl
Futuro – Estudos de perfusao Sen et al. (in review)
Instantaneous wave‐Free Ratio (iFR)
Instantaneous wave‐Free Ratio (iFR) Instantaneous
wave‐Free Ratio (iFR)
Reserva Instantanea de Fluxo
Futuro – Estudos com desfechos
com desfechos clinicos
150
Etico repetir estudos com desfechos clinicos?
Pa and Pd Pressure (mmHg)
A
50
B
C
FAME and FAME II data must be available?
ADVISE team
King’s College London
King’s College London
Simon Redwood
Hospital Clínico San Carlos Javier Escaned
Royal Brompton Hospital
Carlo Di Mario
Imperial College
JJustin Davies, Sayan Sen, Sukhjinder Nijjer, Iqbal Malik, ti D i S
S
S khji d Nijj I b l M lik
Jamil Mayet, Alun Hughes, Darrel Francis, Ghada W Mikhail, Rodney A Foale, Jason Tarkin, Christopher Broyd, Richard Jabbour, Amarjit Sethi, Christopher Baker, Michael Bellamy, Mahmud Al‐Bustami, David Hackett, Masood Khan, David Lefroy, and Kim H Parker.
advisestudy.org
[email protected]
Elegant illustration of errors in identification of the wave‐free
the wave
free window
window
Time delay
04
0.4
0.2
0
3
1502
751
0
750
0
0
Berry C, Pijls N, DeBruyne B, Oldroyd K et al.
y , j ,
y
,
y
2
Measurement in systole
in systole
1.0
0.9
FFR measuremennt 2
0.8
FFR measurement
greyy zone
07
0.7
0.6
0.5
0.4
0.3
0.2
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0.8
0.9
1.0
FFR measurement 1
Classification agreement in (%)
C
(diagnostic accuracy)
100%
90%
80%
70%
60%
50%
40%
0.2
0.3
0.4
0.5
0.6
FFR ranges
0.7