PCI & AimRadial 2018 | Lessons from iFR-SWEDEHEART and DEFINE-FLAIR - Hitoshi Matsuo

1. Lessons from iFR-SWEDEHEART and
DEFINE-FLAIR Hitoshi Matsuo M.D.,PhD.
Department of Cardiovascular Medicine
Gifu Heart Center

2. Disclosures
• Speaker’s name: Hitoshi Matsuo
✓ I have the following potential conflicts of interest to report in the field
of this presentation:
Speaker at educational events and consultancies:
PHILLIPS, BOSTON SCIENTIFIC, Abott Vascular, Zeon Medical, Kaneka

3. Definition of iFR:
Instant wave-free ratio across a stenosis during the wave-free period, when resistance is
naturally constant and minimized in the cardiac cycle
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Pa
Pd
Wave-free period

4. iFR validation studies
2011 20172012 20142013 20162015
“FFR as Gold Standard” studies
ADVISE VERIFY RESOLVE
JUSTIFY-CFR
VU (PET)
ADVISE II
FORECAST
AMC (MPI)
ADVISE REG DEFINE
FLAIR
iFR SWEDEHEART
SNUH
(PET)
TCT2011 April 23rd 2014 First enrollment in GHC

5. AIMRADIAL and PCI workshop 2018
ESC Guideline of coronary revascularization (Neumann, Sousa-Uva et al. 2018)
When evidence of ischemia is
not available, FFR or iwFR are
recommended to assess the
hemodynamic relevance of
intermediate grade stenosis.

6. iFR validation (against FFR)
Johnson N et al. JACC Intv 2016;9:757–67

7. iFR validation studies
2011 20172012 20142013 20162015
“FFR as Gold Standard” studies
“Head-to-head” studies
ADVISE VERIFY RESOLVE
JUSTIFY-CFR
VU (PET)
ADVISE II
FORECAST
AMC (MPI)
ADVISE REG DEFINE
FLAIR
iFR SWEDEHEART
SNUH
(PET)

8. Similar Accuracy
1. Van de Hoef TP et al. Circ Cardiovasc Interv. 2012;5:508-14; 2. Sen S et al. J Am Coll Cardiol. 2013;61:1409-20;
3. Van de Hoef TP et al. EuroIntervention. 2015;11:914-25; 4. Sen S et al. J Am Coll Cardiol. 2013;62:566;
5. Petraco R et al. Circ. Int. 2014;7:492-502; 6. de Waard G et al. J Am Coll Cardiol. 2014;63:A1692.
*HSR: hyperemic stenosis resistance

9. iFR validation studies
2011 20172012 20142013 20162015
“FFR as Gold Standard” studies
“Head-to-head” studies
Clinical outcomes trials
ADVISE VERIFY RESOLVE
JUSTIFY-CFR
VU (PET)
ADVISE II
FORECAST
AMC (MPI)
ADVISE REG DEFINE
FLAIR
iFR SWEDEHEART
SNUH
(PET)

10. DEFINE FLAIR
Primary objective
• Assess safety and efficacy of
decision-making on coronary
revascularisation based on iFR vs
FFR
• Assess if iFR is non-inferior to
FFR when used to guide treatment
of coronary stenosis with PCI
Primary endpoint
• Major adverse cardiac events
(MACE) rate in the iFR and FFR
groups at 30 days, 1 and 2 years.
• MACE (combined endpoint of
death, non-fatal MI, or unplanned
revascularisation)
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11. iFR-Swedeheart
Primary objective
• Assess safety and efficacy of decision-making
on coronary revascularisation based on iFR
vs FFR
• Assess if iFR is non-inferior to FFR when
used to guide treatment of coronary stenosis
with PCI
Primary endpoint
• Major adverse cardiac events (MACE) rate in
the iFR and FFR groups at 30 days, 1 and 2
years.
• MACE (combined endpoint of death, non-fatal
MI, or unplanned revascularisation)
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12. From the largest global physiology studies
• DEFINE FLAIR and iFR
Swedeheart are the new landmark
physiology studies
• 4500+ patients, more than twice
the combined patient population of
previous landmark physiology
studies
– DEFINE FLAIR: n = 2492 patients
– iFR Swedeheart: n = 2037 patients
• 2 prospective, randomized,
controlled trials
• Published in New England Journal
of Medicine
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13. 49 Centers
19 Countries
Global Recruitment

14. DEFINE-FLAIR and iFR SwedeHeart in
clinically meaningful patient distribution
NEJM, (2017)

15. Natural history study of FFR has same distribution
as DEFINE-FLAIR
De Bruyne, Pijls, Johnson, JACC 2016
“A majority of the lesions
were in the intermediate
range of 50% to 69%
diameter stenosis, and of
moderate complexity”

16. Treatment allocations with iFR and FFR
Significantly less revascularisation based on iFR interrogation (P < 0.01)
iFR (n=2240) FFR (n=2246)

17. Similar MACE using either iFR or FFR to guide
revascularization decision-making
MACE similar and low at 1 year after iFR- and FFR-based
revascularisation decision-making
FFR 6.41%
IFR 6.47%
N=4486

18. MACE components in iFR and FFR guided revascularisation
(DEFINE FLAIR + iFR SWEDEHEART)
MACE components similar and low at 1 year after iFR- and FFR-guided
revascularisation decision-making
Outcome
iFR Group
N=2240
no.(%)
FFR Group
N=2246
no. (%)
Hazard Ratio
(95% CI)
P value
Primary outcome: death from any
cause, nonfatal myocardial infarction, or
unplanned revascularisation
145 (6.47) 144 (6.41) 1.03 (0.81-1.31) 0.81
Death from cardiovascular causes 15 (0.67) 10 (0.45) 1.52 (0.68-3.39) 0.3
Death from noncardiovascular causes 21 (0.94) 15 (0.67) 1.42 (0.73-2.76) 0.3
Nonfatal myocardial infarction 53 (2.37) 45 (2.00) 1.19 (0.76-1.85) 0.45
Unplanned revascularisation 93 (4.15) 109 (4.85) 0.91 (0.69-1.21) 0.53

19. iFR-guided strategy significantly reduces
patient discomfort and procedural time
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P < 0.001
3.1%
30.8%
P < 0.001
45.0
40.5
90% Symptoms 10% Time
iFR FFR iFR FFR Davies JE et al.
NEJM 2017

20. Summary of clinical events in deferred patients, stratified into LAD and non-LAD
Sen S , Davies JE et al. in submission
AIMRADIAL and PCI workshop 2018

21. 0
2
4
6
iFR
FFR
MI Peri-procedural
MI
Target Vessel
MI
Non-Target
Vessel MI
Unplanned
Revasc.
Target Vessel
Revasc
Non-Target
Revasc
Unplanned RevascularisationMyocardial Infarction
iFR
FFR
2
4
6
EventRate(%)
p=0.07
p=0.29
p=0.04
p=1.00
p=0.09
p=1.00
p=0.07
Summary of clinical events in LAD deferred patients
Sen S , Davies JE et al. in submission
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22. Kaplan-Meier for MACE in LAD deferred patients.
Sen S , Davies JE et al. in submission
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23. Kaplan-Meier for MACE in non-LAD patients.
Sen S , Davies JE et al. in submission
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24. ACS
Management of non-culprit lesions?
Culprit Lesions PCI
Non-culprit 40-70%
FFR
iFR
Safe?
Safe?

25. iFRFFR
HR 0.74 (0.38-1.43); p=0.37HR 0.52 (0.27-0.99); p<0.05
ACS 6.4%
SCD 3.4%
ACS 5.4%
SCD 3.8%
Safety of Deferral with FFR / iFR
Escaned J, Tanaka N, Yokoi H, Takashima H, Kikuta Y, Matsuo H, Koo BK, Nam CW, SerruysPW, Götberg M,
Davies JE et al.. JACC Cardiovasc Interv. 2018 Aug 13;11(15):1437-1449.

26. Improved Safety with iFR in ACS
FFR
iFR
p<0.05
N=4529 N=674
p=0.026
Masrani Mehta et al. J Am Heart Assoc 2015;4:e002172.
N=576
p<0.0001
Hakeem A, et al. J Am Coll Cardiol 2016;68:1181–91.
Lee JM, Koo BK, et al. Eurointervention 2017;10:4244.
N=1596
p=0.002
p=0.37
Escaned J, Tanaka N, Yokoi H, Takashima H, Kikuta Y, Matsuo H, Koo BK, Nam CW, SerruysPW, Götberg M,
Davies JE et al.. JACC Cardiovasc Interv. 2018 Aug 13;11(15):1437-1449.

27. iFR is more Accurate for Hyperemic Flow indexes even when
Hyperemic Pressure FFR Disagrees with Hyperemic Flow
Cook, Jeremias, Kikuta, Shiono, Stone, Davies et al. J Am Coll Cardiol Cardiovasc Interv 2017.
Jeremias A, Fearon WF, Pijls NHJ et al. RESOLVE. J Am Coll Cardiol 2014;63:1253–61.
iFR (0.99)
FFR (0.74)
iFR (0.83)
FFR (0.83)

28. Health Economics of FFR vs. iFR

29. Significantly Lower Cost with iFR
Lord J, Tanaka N, Yokoi H, Takashima H, Kikuta Y,
Koo BK, Nam CW, Matsuo H, Serruys PW, Escaned J, Patel M, Davies J, et al. ACC.18.
Submitted
Adjusted Δ $896
(p=0.006)
$7442
3500
4000
4500
5000
5500
6000
6500
7000
7500
8000
8500
FFR iFR
$8243 Shorter procedural duration
No hyperaemic medication
Lower PCI rates
Fewer CABG procedures
Fewer Unplanned PCI (LAD)
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30. iFR-SWEDEHEART: Two-year results
Randomized Trial of Instantaneous Wave-Free Ratio vs
Fractional Flow Reserve Guided PCI
Ole Fröbert, MD, PhD
- on behalf of the iFR SWEDEHEART investigators

31. Enrollment 22.0% mean use of iFR/FFR in
stable angina in SCAAR - 2015

32. Composite
Endpoint at
2 years
(Death, MI,
Unplanned revasc.)
log-rank p = 0.93

33. Mortality at
2 years
log-rank p = 0.88

34. Myocardial
infarction at
2 years
log-rank p = 0.758

35. Unplanned
revasc. at
2 years log-rank p= 0.854

36. Mace deferred patients
Escaned, J et al,
JACC Cardiovasc Interv
2018, 11: 1437

37. Subgroup
analysis at
2 years
FFR iFR

38. Conclusions
iFR-SWEDEHEART demonstrated overall similar clinical
event rates between iFR and FFR at 2-year follow-up
Subgroup analysis suggests increased event rates among
diabetic patients evaluated with FFR
iFR upgraded to class IA in newest European Society of
Cardiology Guidelines on myocardial revascularization *)
*) European Heart Journal 2018, doi:10.1093/eurheartj/ehy394

39. AIMRADIAL and PCI workshop 2018
ESC Guideline of coronary revascularization (Neumann, Sousa-Uva et al. 2018)
When evidence of ischemia is
not available, FFR or iwFR are
recommended to assess the
hemodynamic relevance of
intermediate grade stenosis.

40. iFR Installation in Japan
49
421
614
705
817
867
2013 2014 2015 2016 2017 2018
Unit
Cumulative Installation
● 2018
● 2017
● 2016
● 2015
● 2014
● 2013
(As of June 30, 2018)

41. Pressure pullback using iFR
Hitoshi Matsuo MD.PhD.
Department of Cardiovascular Medicine
Gifu Heart Center

42. AIMRADIAL and PCI workshop 2018

43. AIMRADIAL and PCI workshop 2018

44. AIMRADIAL and PCI workshop 2018

45. Saito N, Matsuo H et al. J Invasive Cardiol. 2013 Dec;25(12):642-9..
In Vitro Assessment of Mathematically-Derived FFR
in Coronary Lesions With More Than Two Sequential Stenoses
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46. In Vitro Assessment of Mathematically-Derived FFR
in Coronary Lesions With More Than Two Sequential Stenoses
iFR(X-)=iFRpre+ΔiFR(X)
iFR（X)Pred＝１－ΔiFR(X)AIMRADIAL and PCI workshop 2018

47. Case: M.M. ID: 334928 74 y.o. female
Coronary risk factors: HTN (-), DM (+), HL (+), Family Hx (+), Smoking (+)
PH: none, FH: Brother (cardiac death)
PI: The patient was referred to our hospital due to the suspicion
of angina pectoris. Coronary angiogram performed on 2016/2/12 showed
severe coronary stenosis in her coronary artery showed diffuse calcified coronary stenosis
both in RCA and LCA.(#1: 90%, #2 90%, #3 75%, #6, #14 90%.

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49. AIMRADIAL and PCI workshop 2018
Matsuo H, Kawase Y. Cardiovasc Interv Ther. 2016 Jul;31(3):183-95.

50. FOCAL
DIFFUSED
(low pressure drop intensity)
iFR pullback mapping to identify focal and diffuse
disease
FOCAL
(high pressure drop intensity)
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51. SyncVision Installation in Japan
3
27
54
2016 2017 2018
Unit
Cumulative Installation
● 2018
● 2017
● 2016
(As of June 30, 2018)

52. FFR/iFR mapping: How It Works…
Dynamic calibration factor for each section of the roadmap allows
accurate measurement even in cases of foreshortening based on known
tip length (accuracy <2.5mm)
Recommendation
Fluoro Rate: 15 fps
Pullback speed: <2.0mm/sec

53. Case presentation
 75 years old male
 Effort Angina
 PI: The patient was referred to our hospital due to the
exaggerated chest pain during effort.
 Risk factors : past smoker, HT,DM,Dyslipidemia
 No prior intervention
 LVEF 60% CKD class 2
 Transient perfusion defect in anteroseptal wall by
SPECT
 Angiography showed LAD proximal and mid stenosis.

56. Predicted iFR
0.78
Just click and drag
for length measurement and iFR drop
within that lesion

57. Predicted iFR
0.50

58. Predicted iFR
0.91

59. 3.0mm*28mm length EES
3.0mm*24mm length EES

61. post iFR
0.91
Predicted iFR
0.91

62. Message from DEFINE FLAIR and iFR SwedeHeart
 iFR and FFR guide decision making have similar
clinical outcomes at 2year.
 Deferral using iFR or FFR is very safe.
 iFR has shorter time.
 iFR is more patient friendly.
 iFR deferral is possibly safer in ACS patients.
 LAD deferral by iFR is not risky and might be
safer than deferral by FFR.
 Co-registration is only possible with iFR.
 iFR is now recommended as class1A in the
ESC revascularization guideline 2018.

63. AIMRADIAL and PCI workshop 2018
Thank you for your attention!!!