This document discusses various methods for assessing coronary artery disease, including iFR, FFR, and resting gradients like Pd/Pa. It summarizes recent clinical trials comparing these techniques. The key points are: 1) Resting indices like iFR and Pd/Pa provide equivalent information to each other but differences remain when compared to FFR, especially for proximal left anterior descending artery lesions. 2) Trials comparing iFR to FFR did not definitively show iFR was non-inferior in reducing hard clinical outcomes like death and myocardial infarction. 3) Contrast-enhanced FFR may be superior to resting indices as it has the highest correlation with FFR and best diagnostic accuracy.

1. Pd/Pa, iFR and resting
gradients: how do they
relate?
Prof. Colin Berry
Golden Jubilee National Hospital,
University of Glasgow.
AIMRADIAL 2018, Sarasota Memorial Hospital
28 November 2018

2. Body text
Disclosures
Institutional agreements between the University of
Glasgow (employer) and Abbott Vascular,
AstraZeneca, Coroventis, DalCor, GSK,
HeartFlow, Novartis, and Philips.
Colin Berry, 28.11.2018

3. Body text
1.Current guidelines
2.Accuracy & performance
3. Clinical studies
Learning objectives
Colin Berry, 28.11.2018

4. Body text
ESC guideline, myocardial
revascularisation, 2018
Recommendation on functional testing & lesion assessment
Colin Berry, 28.11.2018

5. Body text
Physiological tests in ACS
Guidewire sensor
Flow-limiting CAD Microvasculature
FFR IMR
C-FFR CFR
NHPR (Pd/Pa, iFR, DPR, RFR, etc)

6. Colin Berry, 28.11.2018

7. iFR reduces with
0.82
0.64
n = 200
Berry C et al JACC 2013
VERFIY - iFR reduces with hyperaemia
iFR is not independent of adenosine
Colin Berry, 28.11.2018

8. Sensitivity
0.00
0.25
0.50
0.75
1.00
1-Specificity
0.00 0.25 0.50 0.75 1.00
iFR Pd/Pa
AUC 0.81 0.82
Cut-off Value 0.90 0.92
iFR for FFR ≤ 0.8
Pd/Pa for FFR ≤ 0.8
RESOLVE meta-analysis: FFR vs. iFR or Pd/Pa
Colin Berry, 28.11.2018

9. Body text
Discordance, FFR- vs. iFR
Proximal vs. distal LAD
Colin Berry, 28.11.2018
Hennigan, Berry, Oldroyd, et al Circ CV Interven 2017

10. Body text
Discordance, FFR- vs. iFR
VERIFY-2: Proximal vs. distal LAD
197 patients, 257 stenoses; 148 (58%) LAD
Consecutive, prospectively enrolled.
Colin Berry, 28.11.2018
Hennigan, Berry, Oldroyd, et al Circ CV Interven 2017

11. Body text
VERIFY-2 population, Glasgow, n=197
iFR VOLCANO Harvest Software
Van’t Veer et al J Am Coll Cardiol 2017
Colin Berry, Oxford, October 2018

12. Body text
Comparison of 6 resting indices
vs. iFR®
Van’t Veer et al J Am Coll Cardiol 2017Colin Berry, Oxford, October 2018

13. Body text
Correlations vs. iFR®
approximate line of unity
Van’t Veer et al J Am Coll Cardiol 2017

14. Body text
AUC
> 0.995
6 resting indices vs. iFR®
Van’t Veer et al J Am Coll Cardiol 2017

15. New resting
indices ?

16. DPR approximates diastole
by selecting the portion of
the cardiac cycle below
mean Pa with a down-
sloping pressure
DPR

17. Johnson, Li, Chen, Berry et al 2018

18. Pause for
thought …
Colin Berry, Oxford, October 2018

19. Body text
Berry C, Circulation 2017
90 70

20. Body text
Data
N = 2159, iFR n=95 withdrawn
N = 2186, FFR n=71 withdrawn
iFR vs. FFR
27 fewer patients
112 fewer PCI / CABG
Excess of death / MI events @ 1 year
Fragility test, n=4 for p<0.05
Berry C, Circulation 2017

21. Body text
oo
DEFINE-FLAIR, iFR-SWEDE-HEART
Open-label, investigator-actioned primary
outcome, susceptible to bias …
Time-course for FFR events
– excess of iatrogenic MI (↑ PCI)
– flat line MACE, from 30 – 60 days
MACE- DEFINE-FLAIR
Investigator vs. spontaneous
MACE = death, non-fatal MI, or unplanned
revascularisation
“Revascularisation will be considered “unplanned”
when it was not … identified at the time of the index
procedure as a staged procedure to occur within
60 days.”
PCI Day 59 intended vs day 60+ primary
outcome
?

22. Body text
oo
DEFINE-FLAIR, iFR-SWEDE-HEART
Open-label, investigator-actioned primary
outcome, susceptible to bias …
Time-course for FFR events
– excess of iatrogenic MI (↑ PCI)
– flat line MACE, from 30 – 60 days
MACE- DEFINE-FLAIR
Investigator vs. spontaneous
MACE = death, non-fatal MI, or unplanned
revascularisation
“Revascularisation will be considered “unplanned”
when it was not … identified at the time of the index
procedure as a staged procedure to occur within
60 days.”
Primary outcome
PCI - Day 59 “no” vs. day 60+ “yes”

23. Body text
o
Open-label trial, clinician-reported primary outcome,
MACE = death, non-fatal MI, or unplanned revascularisation
“Revascularisation will be considered “unplanned” … a staged
procedure to occur within 60 days.”
Revascularisation: 93 (iFR) vs 109 (FFR)↑
Death & MI: 90 (iFR) vs. 70
Revasc. n = 202 >> death & MI, n=160
- dominates primary outcome
DEFINE-FLAIR, iFR-SWEDE-HEART
Susceptible bias, Type 1 error by design
Time-course for FFR events
Excess of iatrogenic MI (↑ PCI)
~1 MACE, 30–60 days, then ↑ > 60 days
MACE- DEFINE-FLAIR
Investigator vs. spontaneous

24. Composite
Endpoint at
2 years
(Death, MI,
Unplanned revasc.)
log-rank p = 0.93
iFR-SWEDEHEART: Two-year results

25. C-FFR highest correlation with FFR
ROC highest for C-FFR
CONTRAST JACC CV Intervention 2016
CONTRAST

26. Body text
Conclusions
1. Resting indices are equivalent, any may be
used, … NHPR
2. Differences remain vs. FFR e.g. prox. LAD
disease, where decision making important
3. Non-inferiority in iFR trials for hard
outcomes is not confirmed.
4. ? Avoid using adenosine (85% cases), use
contrast-FFR, superior to resting indices

27. Thank you for
your attention

28. Cx
Cx
LAD
Clinical conundrums: which lesion(s) to treat ?
Can functional testing reduce practice variation ?
Subjective visual interpretation
Colin Berry, 28.11.2018

29. Body text
DEFINE-FLAIR LAD analysis
1.Patients not stratified by LAD
2.Not pre-specified
3.Post-hoc analysis
4.Investigator led
5.‘All LAD’ not proximal LAD
6.Investigator-reported revascularisation dominated
the event rate.
7.MACE - susceptible to ascertainment bias