2. FFR – Gold Standard Physiological Index
FFR is supported by European (class I, level of evidence: A ) and U.S. guidelines
(class Ⅱa, level of evidence: A ) for assessing intermediate coronary lesions and
guiding revascularization decisions.1,2)
TCT 2019
But still…global adoption of FFR remains low.
Wakayama Medical University
1) 2018 ESC/EACTS Guidelines on myocardial revascularization 2) 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention
3. Sonuçlar
• Farmakolojik hiperemi indüksiyonu olsun veya olmasın, koroner anjiyografiden (QFR)
FFR'nin hızlı hesaplanması mümkündür.
• Konvansiyonel tanısal koroner anjiyografiye dayalı kontrast akışlı QFR (cQFR), hiperemik
koşullara dayalı QFR'ye benzer sonuçlar sağlar ve sabit akışlı QFR'den üstündür. .
• cQFR'nin olumlu sonuçları, daha geniş bir FFR bazlı lezyon değerlendirmesi benimseme
potansiyeli taşımaktadır, çünkü cQFR prosedür süresini, riskini ve maliyetlerini azaltabilir
(basınç teli kullanmaya gerek kalmadan ve maksimum hiperemiyi indüklemeye gerek
kalmaz)
• Güncel endikasyonlar: Stabil anjina olan hastalar;
• Devam eden araştırmalar : MI, bifurkasyon lezyonları, uzun diffüz hastalık, vb.
4. Paradigm Shift: HeartFlow® FFRCT Analysis
Coronary CTA + the HeartFlow Analysis is the only non-invasive cardiac pathway to
provide both anatomical and lesion-specific functional information in a single patient
encounter
Anatomical
Information
Patient management guided by lesion-specific physiology led to a
28% reduction in MI in a meta-analysis of multiple invasive FFR studies1
Functional
Insight
HeartFlow
Model
+ =
5
1. Zimmerman, et al. Euro Heart J 2019. DOC 56816634
5. FFRCT uses A.I. Deep Learning methods for image analysis
Image data
from CTA
Deep learning algorithm used
to create anatomic model
Trained analysts
inspect & correct
Approved model
delivered
Supercomputers apply CFD to
create physiologic model
Virtuous cycle where human
corrections are used in
subsequent releases to train
the algorithm, the algorithm
improves and fewer
corrections are needed
DOC 56816634
6. FFRCT Image segmentation methods validated with OCT data
and robust even in patients with high calcium scores
Uzu et.al. EuroIntervention. 2019;14:e1609-e1618. Nørgaard B et al, JACC Imaging 2015
Ag =3865
DOC 56816634
7. Computational Model
based on CCTA
3-D anatomic model from CCTA
No additional imaging No
additional medications
Blood Flow Solution
Blood flow equations solved
on supercomputer
Physiologic models
-Myocardial demand
-Morphometry-based boundary condition
-Effect of adenosine on microcirculation
CT-derived computed FFR
(FFRCT)
FFRCT = 0.72
(can select any point on
model)
Koo BK. EuroPCR 2011
Patient-specific non-invasive FFR using CT & CFD
Seoul National 8
8. Clinical Evidences on Diagnostic Performance
• DISCOVER-FLOW
5 center FIH clinical trial
Completed 2011
N=103 patients
Published in JACC
• DeFACTO
17 center clinical trial
Completed 2012
N=252 patients
Published in JAMA
• NXT
10 center clinical trial
Completed August, 2013
N=251 patients Published
in JACC
Seoul National 9
10. Diagnostic performance of coronary diagnostic tests vs. FFR
Stress Echo
SPECT
cCTA
FFRCT
Norgaard et. al. J Eur Radiology 2015.
Seoul National 8
11. Per-Patient Diagnostic Performance
95% CI
FFRCT
CT
95% CI
67-78
58-70
95% CI
84-95
77-90
95% CI
46-83
34-51
95% CI
60-74
53-67
95% CI
74-90
61-81
FFRCT <0.80
CT >50%
N=252
%
12. Discrimination
Per-Patient Per-Vessel
FFRCT 0.81 (95% CI 0.75, 0.86)
CT 0.68 (95% CI 0.62, 0.74)
FFRCT 0.81 (95% CI 0.76, 0.85)
CT 0.75 (95% CI 0.71, 0.80)
Greater discriminatory power for FFRCT versus CT stenosis
Per-patient (Δ 0.13, p<0.001)
Per-vessel (Δ 0.06, p<0.001)
AUC AUC
*AUC = Area under the receiving operating characteristics curve
13. FFR 0.65
= Lesion-specific ischemia
FFRCT 0.62
= Lesion-specific ischemia
LAD stenosis
FFRCT 0.87
= No ischemia
RCA stenosis
FFR 0.86
= No ischemia
Case Examples: Obstructive CAD
Case
1
Case
2
CT ICA and FFR FFRCT
CT FFRCT
ICA and FFR
14. 95% CI
FFRCT
CT
95% CI
61-80
63-92
95% CI
63-92
53-77
95% CI
53-77
53-77
95% CI
39-68
20-53
95% CI
75-95
55-79
Per-Patient Diagnostic Performance for
Intermediate Stenoses by CT (30-70%)
N=83
FFRCT <0.80
CT >50%
16. 30%
40%
50%
60%
70%
80%
90%
100%
30% 40% 50% 60% 70% 80% 90% 100%
Specificity
Sensitivity
Adapted from Nørgaard B et al. Euro Radiology 2015;25:2282-90
FFRCT Accuracy (from NXT)
Performance of coronary diagnostic tests vs. FFR
TAG
Stress Echo
SPECT
Coronary CTA
CMR
FFR (reference standard)
FFRCT
FFRCT
IVUS
Invasive Angiography
• Specificity: 86%
• Sensitivity: 84%
• Accuracy: 86%
17. PACIFIC: 208 pts underwent CTA, SPECT,
PET, and routine 3-vessel invasive FFR
FFRCT was analyzable in 180 pts (87%)
Knaapen P et al. EuroPCR 2018
Relationship between FFR and FFRCT
FFR ≤0.80 in 81 pts (45%); FFRCT ≤0.80 in 114 pts (63%)
3%
10%
63%
24%
Sensitivity:
90%
Specificity:
86%
Accuracy:
87%
0.9
0.4 0.6 0.7 0.8 1.0
0.4
0.8
1.0
0.5
0.5
0.6
0.7
0.9
FFR
CT
FFR
Y = 0.65*X + 0.25
R = 0.80
p < 0.001
18. Knaapen P et al. EuroPCR 2018
Sensitivity, specificity and accuracy vs. invasive FFR
FFR ≤0.80 in 81 pts (45%); FFRCT ≤0.80 in 114 pts (63%)
100-Specificity
Sensitivity
100
40
0
80
60
20
0
20 40 60 80 100
FFRCT AUC 0.94 (0.92-0.96)
PET AUC 0.87 (0.83-0.90)
CT AUC 0.83 (0.80-0.86)
SPECT AUC 0.70 (0.65-0.74)
PACIFIC: 208 pts underwent CTA, SPECT,
PET, and routine 3-vessel invasive FFR
FFRCT was analyzable in 180 pts (87%)
19. PLATFORM: Invasive Arm
584 pts with new onset CP were prospectively assigned to usual
testing (n=287) or FFRCT-guided testing (n=297) in different time
periods. Local site decided ICA would be performed in 380 pts.
Douglas PS et al. Eur Heart J 2015;36:3359–67
Non-obstructive CAD
Obstructive CAD
Usual Care (n=187)
27%
73%
FFRCT-Guided (n=193)
27%
12%
61%
No ICA
performed
83% reduction
P<0.0001
Primary endpoint was catheterization without obstructive CAD:
73.4% with Usual Care vs. 12.4% with FFRCT Guidance, P<0.0001
20. PLATFORM
Invasive: 1-
Year
Outcomes
Douglas PS et al. JACC 2016;68:435–45
Usual Care
(n=187)
FFRCT Guidance
(n=193)
P value
MACE 2 (1.1%) 2 (1.0%)* 0.99
- Death 1 (0.5%) 0 (0%)
- Non-fatal MI 1 (0.5%) 1 (0.5%)
- Hosp w/urg revasc 0 (0%) 1 (0.5%)
Cum. Radiation, mSv 10.4 ± 6.7 10.7 ± 9.6 0.21
Total costs, mean (FFRCT
= $0)
$12,145 $8,127 <0.0001
Total costs, mean (FFRCT
= $1400**)
$12,145 $8,975 <0.0001
*Among 117 pts whose planned ICA was cancelled on the basis of FFRCT,
only 4 underwent ICA during 1-year FU, and MACE = 0%. **Current ASP
21. PLATFORM Invasive: 1-Yr Resource Use
Usual Care
(n=187)
FFRCT-Guided
(n=193)
Noninvasive tests
Stress electrocardiography 17 19
Stress echocardiography 5 6
Stress nuclear 6 3
Magnetic resonance imaging 6 3
Coronary CT angiography 1 194
FFRCT 0 117
Invasive procedures
Diagnostic ICA 159 44
ICA with PCI 44 55
FFRINV 12 29
Intravascular ultrasound 8 5
Optical coherence tomography 3 1
Coronary revascularization
PCI 49 55
Bypass surgery 18 10
Total hospital days 514 283
Clinic visits 162 111
Douglas PS et al. JACC 2016;68:435–45
67 65
22. Geometry of the diseased segment on the original
computational model is virtually remodeled to enlarge the
radius of the lumen according to the proximal and distal
reference area to mimic the effects of a stent.
Computational analysis of coronary pressure and flow is
repeated to determine post-treatment FFRCT blinded to
invasive FFR results.
Ihdayhid AR et al. JACC Int 2017
FFRCT Planner Application: Virtual Stenting
23. Lesions in ostial LCX
and mid LCX
PCI Planner predicted
only mid- LCX lesion
required stenting
Confirmed by FFR
during the actual case
Kim KH et al.
JACC Intv 2014;7:72-8
FFRCT Planner Application: Virtual Stenting
24. Kim KH et al. JACC Intv 2014;7:72-8
FFRCT Planner Superior to FFR? Case report #1
Operator did not cover LAD ostial lesion – confirmed by IVUS. FFR 0.74.
PCI Planner predicted FFR 0.76 if the ostium
was untreated vs. 0.81 if ostium was stented
25. FFRCT Planner Superior to FFR? Case report #2
Ihdayhid AR et al. JACC Int 2017
Baseline After stent lesion B After stent lesion A
26. Ihdayhid AR et al. JACC Int 2017
Stent lesion A only
FFRCT Planner Superior to FFR? Case report #2
Better strategy:
Baseline
27. Ihdayhid AR et al. JACC Int 2017
Stent lesion A only
FFRCT Planner Superior to FFR?
Better Strategy:
Baseline
After virtually stenting
lesion A
28. PI: Gregg W. Stone
AROs: CRF and DCRI; Sponsor: HeartFlow
~5000 troponin negative pts in whom
angiography is planned for suspected CAD
Study FFRCT
(blinded, w/o incidental findings)
R
Angiography
(FFRCT stays blinded)
(n=2500)
FFRCT guidance
(FFRCT is unblinded)
(n=2500)
1:1
DECISION Trial
A multicenter randomized trial of FFRCT-guided selective angiography
and FFRCT-guided revascularization compared with routine
angiography and FFR/iFR-guided revascularization in pts with
suspected CAD in whom angiography is intended
29. NHPR = Non-Hyperemic Pressure Ratio: iFR, RFR, dPR, dFR
DECISION Trial
Guideline-directed medical therapy; FU @ 45 days, 6 months, 1 year and 2 years
FFR/NHPR-guided
revascularization
Angiography
(FFRCT stays blinded)
(n=2500)
Plaque rupture, LM stenosis ≥30%, or FFRCT ≤0.80
FFRCT guidance
(FFRCT is unblinded) (n=2500)
Yes
No,
all other
Defer Cath
mandatory
Angiography, FFRCT
guided revascularization
No, but typical angina
and FFRCT 0.81-0.85
Heart Team meeting
FFRCT planner
Angiography mandatory
Heart Team meeting
FFRCT planner
Angiography optional
Defer Cath
Medical Rx
FFR/NHPR allowed but not recommended
30. Primary endpoints (sequentially tested):
1) 2-year MACE1: all-cause death, MI, or ischemia-driven
revascularization (time-to-first event, powered for noninferiority)
2) 2-year MACE2: all-cause death, MI, all revascularization, cardiac
catheterization without actionable cardiac pathology (requiring
transcatheter or surgical cardiac intervention within 30 days)
(Finkelstein-Schoenfeld hierarchical testing, powered for superiority)
Secondary powered endpoints (sequentially tested):
1) 2-year rate of cardiac catheterization without actionable cardiac
pathology (time-to-first event, powered for superiority)
2) 2-year total costs (powered for superiority)
DECISION Trial
31. • CTA w/FFRCT provides data on coronary anatomy and physiology
which more strongly correlates with invasive FFR than any other
non-invasive diagnostic test
• Non-randomized studies suggest deferral of ICA in pts with
negative FFRCT may safely obviate unnecessary ICA
• The FFRCT Planner has been developed to allow the local heart
team to reach revascularization decisions prior to ICA, and provide
interventional guidance for PCI procedures w/o the need for
invasive physiology
• The DECISION Trial is a large-scale randomized study which will
determine whether FFRCT-guidance with use of the FFRCT Planner
in pts in whom ICA is otherwise planned may safely defer
unnecessary cardiac catheterization procedures while improving
overall clinical outcomes and reducing costs
Conclusions
32. How can this novel technology change our daily practice?
CCTA Invasive angiography FFR
>50% diameter stenosis >50% diameter stenosis FFR 0.74 P
C
I
FFR
>50% diameter stenosis
FFR 0.84
Medical treatment
>50% diameter stenosis
FFR
Current pathway
Seoul National 33
33. Novel (risk-free, non-invasive, cost-saving) pathway
CCTA Invasive angiography and PCI
FFRCT
>50% diameter stenosis FFRCT 0.74 Invasive procedures
0.74
0.85
FFR
>50% diameter stenosis FFR 0.84 no ischemia
>50% diameter stenosis
How this novel technology can change our daily practice?
PCI
Medical
treatment
Seoul National 34
34. Planning the treatment strategy using
Virtual revascularization & CT-derived computed FFR
FFRCT after virtualstenting
From CTA to FFRCT and its beyond…
Seoul National
Kim KH, Koo BK, et al. JACC interv 2014
35
35. Before
Stenting
After
Stenting
CT-derived computed FFR
(FFRCT)
▲FFRCT 0.12
▲FFRCT 0.11 FFRCT 0.72
▲FFRCT 0.02
Myocardial ischemia +
Angiography Invasive FFR
Myocardial ischemia +
Stent
Planning the treatment strategy using
Virtual revascularization & CT-derived
computed FFR
Seoul National
Kim KH, Koo BK, et al. JACC interv 2014
36
36. Before
Stenting
After
Stenting
Angiography Invasive FFR
No residual ischemia
CT-derived computed FFR
(FFRCT)
FFRCT 0.72
Stent
FFRCT 0.86
No residual ischemia
▲FFRCT 0.12
▲FFRCT 0.11
▲FFRCT 0.02
Myocardial ischemia +
Myocardial ischemia +
Stent
Planning the treatment strategy using
Virtual revascularization & CT-derived computed FFR
Seoul National
Kim KH, Koo BK, et al. JACC interv 2014
37
37.
38.
39.
40. ESC CONGRESS2013
TCT 2019
ESC CONGRESS2013
Wakayama Medical University
FFRCT – Non-invaziv Fizyolojik İndeks
Anatomik + İşlevsel
Off-site supercomputing
Non-invasive
Gatekeeper
1) Koo et al. J Am Coll Cardiol 2011;58:1989–97 2) Min et al. JAMA 2012;308:1237-1245,
41. ESC CONGRESS2013
TCT 2019
JACC: Cardiovascular Interventions Volume 12, Issue 20, October 2019
Amaç
Hem QFR hem de FFRCT, anatomik bilgiden hesaplanan fonksiyonel endekslerdir,
ancak hesaplama algoritmaları farklıdır.
Referans standardı olarak FFR kullanarak, QFR ve FFRCTarasındaki teşhis performansını
karşılaştırmak için.
43. ESC CONGRESS2013
Vaka 1 – 65 y K
CVIT 2018 ESC CONGRESS2013
TCT 2019
Klinik tanı
KAH
Klinik geçmişi
Semptom yok
LVEF: 55%
Kr: 0.5, eGFR: 65
Koroner risk faktörleri
HT, DLP
Wakayama Medical U ESC CONGRESS
44. ESC CONGRESS2013
Hedef damar: RCA - CCTA, FFRCT , Anjiyografi &QFR
CVIT 2018 ESC CONGRESS2013
TCT 2019
FFRCT: 0.83 FFR: 0.82 QFR: 0.83
70-90% stenosis
FFRCT
CCTA CAG QFR
%DS=58%
Wakayama Medical U ESC CONGRESS
45. ESC CONGRESS2013
Vaka 2 – 72 y E
CVIT 2018 ESC CONGRESS2013
TCT 2019
Klinik tanı
Stable AP
Klinik geçmişi
Eforla göğüs ağrısı
LVEF: 60%
Kr: 0.6, eGFR: 75
Koroner risk faktörleri
HT, DLP
Wakayama Medical U ESC CONGRESS
46. ESC CONGRESS2013
Hedef damar : LAD - CCTA, FFRCT , Anjiyografi &QFR
CVIT 2018 ESC CONGRESS2013
TCT 2019
FFRCT: 0.73 FFR: 0.73 QFR: 0.74
50-70% stenosis
CCTA FFRCT CAG QFR
Wakayama Medical U ESC CONGRESS
47. ESC CONGRESS2013
Vaka 3 – 45 y E
CVIT 2018 ESC CONGRESS2013
TCT 2019
Klinik tanı
KAH
Klinik geçmişi
Semptom yok
LVEF: 60%
Kr: 0.6, eGFR: 75
Koroner risk
faktörleri
HT, DLP, Sigara
Wakayama Medical U ESC CONGRESS
48. ESC CONGRESS2013
Hedef damar : RCA - CCTA, FFRCT , Anjiyografi &QFR
CVIT 2018 ESC CONGRESS2013
TCT 2019
FFRCT: 0.75 FFR: 0.92 QFR: 0.86
30-49% stenosis
CCTA CAG QFR
FFRCT
0.76
0.99
Wakayama Medical U ESC CONGRESS
49. Lesions in ostial
LCX and mid LCX
PCI Planner
predicted only mid-
LCX lesion required
stenting
Confirmed by FFR
during the actual
case
Kim KH et al.
JACC Intv 2014;7:72-8
FFRCT Planner Application: VirtualStenting
50. Kim KH et al. JACC Intv 2014;7:72-8
FFRCT Planner Superior to FFR? Case report #1
Operator did not cover LAD ostial lesion – confirmed by IVUS. FFR0.74.
PCI Planner predicted FFR 0.76 if the ostium
was untreated vs. 0.81 if ostium was stented
51. FFRCT Planner Superior to FFR? Case report #2
Ihdayhid AR et al. JACC Int2017
Baseline After stent lesion B After stent lesionA
52. Ihdayhid AR et al. JACC Int 2017
FFRCT Planner Superior to FFR? Case report #2
Better strategy:
Stent lesion A only
Baseline
53. Ihdayhid AR et al. JACC Int 2017
FFRCT Planner Superior toFFR?
Better Strategy:
Stent lesion A only
Baseline
After virtually stenting
lesion A
54. 55
FFRCT improved patient referral to ICA
Fairbairn, T.A., et al. Euro Heart J 2018 | Douglas, P.S. et al. J Am Coll Cardiol. 2016
All MACE included above (Death, MI, Hospital Admission for ACS and Unplanned Revascularization)
72.3% of patients
who had a positive
HeartFlow Analysis
(FFRCT≤0.80) and were
undergoing ICA
were revascularized
Revascularization
Patients with
suspected CAD
Invasive coronary
angiography (ICA)
No obstructive
disease found
Usual care path
Patients with
suspected CAD
Invasive coronary
angiography (ICA)
No obstructive
disease found
Revascularization
No need for ICA
CTA/FFRCT-Guided Cohort
Usual Care Cohort
CTA /
FFRCT
Obstructive Disease
Obstructive Disease
T H E P L A T F O R M T R I A L
ADVANCE
DOC 56816634
55. Patients have better outcomes with higher Post-PCI FFR
%
Adverse
Events
FFR Post-PCI
Fewer Adverse Events & 40% Reduction in Post-PCI MACE
1. Pijls NHP et al. Circulation 2002; 105: 2950-2954.
2. Johnson N et al. Prognostic Value of FFR: Linking Physiologic Severity to Clinical Outcomes. J Am Coll Cardiol 2014; 64:1641-1654.
Survival curves
0.83 (0.79-0.86)
Post- PCI FFR Values
0.92 (0.90-0.93)
0.98 (0.96-1.00)
%Adverse Events at 6 Months
DOC 56816634
56. HeartFlow Planner
• Noninvasive interactive tool that leverages the information
within the HeartFlow Analysis
• Explore different clinical scenarios by virtually modifying the
vessel
• Assess the FFRCT value(s) resulting from each scenario
Enables the Interventionalist to evaluate alternate treatment strategies to optimize coronary
blood flow before they enter the catheterization lab
*Investigational Device. Not for clinical use.
DOC 56816634
57. Core Components
HeartFlowAnalysis
1 Interactive Mobile Platform
● IOS, interactive viewer
● Cath-lab specific features (e.g. projection
angles)
2
IdealGeometry
3
● Contains a second anatomic
model representing the
“ideal” vessel
Real-time FFRCT
calculation
4
● Modified vessel combined with
updated physiology
● Updated FFRCT values calculated
based on these inputs in seconds
HeartFlow Planner
*Not for clinical use. DOC 56816634
*Investigational Device. Not for clinical use.
58. Case Report
Ihdayhid AR et al. JACC Int 2017 DOC 56816634
*Investigational Device. Not for clinical use.
59. 60
Recent paper – Revascularization of Serial Lesions
“A novel noninvasive FFRCT-based PCI
planner tool more accurately predicts the
true FFR contribution of each stenosis in
serial coronary artery disease”
DOC 56816634
*Investigational Device. Not for clinical use.
60. ESC CONGRESS2013
Klinik Uygulama İçin Çıkarımlar – QFR & FFRCT
CVIT 2018 ESC CONGRESS2013
TCT 2019
FFRCT temel olarak ayaktan tedavi ortamında kullanılır ve gereksiz tanı
anjiyografisi sayısını azaltır.
FFRCT koroner anjiyografi öncesi karar verici olarak
QFR, koroner anjiyografi sırasında elde edilir ve fonksiyonel olarak anlamlı
lezyonları tanımlayarak revaskülarizasyonda karar verilmesine yardımcı
olur.
QFR prosedür süresini, riskini ve maliyetlerini azaltabilir, çünkü basınç teli
kullanmaya ve maksimum hiperemiyi uyarmaya gerek yoktur.
FFRAnjiyo ile optimal stent seçimi ve sayısını sağlamak mümkündür
Wakayama Medical U ESC CONGRESS
61. Sonuç
ESC CONGRESS2013
TCT 2019
Hem QFR hem de FFRCT, koroner darlığın fonksiyonel ciddiyetini doğru bir
şekilde değerlendirme yeteneğine sahiptir.
Wakayama Medical U ESC CONGRESS
