1. Fractional Flow Reserve: How to use FFR in 2015
William F. Fearon, MD
Associate Professor of Medicine
Director, Interventional Cardiology
Stanford University Medical Center

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest /arrangement or affiliation with the organization(s) listed below
Affiliation/Financial Relationship Company
Grant/ Research Support: St. Jude Medical/Medtronic
Grant/ Research Support: NIH-R01 HL (PI)
Consulting Fees/Honoraria: Medtronic
Major Stock Shareholder/Equity Interest:
Royalty Income:
Ownership/Founder:
Salary: NIH-R01 HL (PI)
Intellectual Property Rights:
Other Financial Benefit (minor stock options): HeartFlow

3. How to use FFR in 2015:
When to measure FFR
How to measure FFR

4. When to measure FFR: All angiograms? Multivessel CAD ACS
Left main disease
Stable angina patients
When not to FFR

5. When to measure FFR:
200 stable patients referred for coronary angiography underwent routine FFR in all patent vessels. Treatment plan pre and post FFR compared.
Curzen, et al. Circ Cardiovasc Interv 2014;7:

6. FFR for All Angiograms?
Curzen, et al. CircCardiovasc Interv 2014;7:
200 stable patients referred for coronary angiography underwent routine FFR in all patent vessels. Treatment plan pre and post FFR compared.
Overall the management plan was changed in 26% of cases.

7. FFR for All Angiograms?
1,075 consecutive patients undergoing FFR at 20 French centers
Van Belle, et al. Circulation 2014;129:

8. FAME Study: One Year Outcomes
1,005 patients with multivessel CAD randomized to FFR or Angio-guided PCI
p=0.02
p=0.04 %
~40% 
~35% 
~30% 
Tonino, et al. New Engl J Med 2009;360:

9. FAME: Economic Evaluation
Bootstrap Analysis
FFR-guided PCI saved >$2,000 per patient at one year compared to Angio-guided PCI
Circulation 2010;122:

10. Anatomic vs. Functional CAD
Angiographic
3 Vessel
Disease
0VD (9%)
3VD (14%)
1VD (34%)
2VD (43%)
Tonino, et al. J Am Coll Cardiol 2010;55:

11. Functional SYNTAX Score
Discriminates Risk for Death/MI
P < 0.01
32% of
patients
20% of
34% of
patients
59% of
Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8

12. FAME 3 Trial: All Comers with 3 V CAD (not involving LM)
Heart team identifies lesions for PCI/CABG
and then patient is randomized
FFR-Guided PCI with DES
Stent all lesions with FFR ≤ 0.80
(n=750)
Perform CABG based on
coronary angiogram
(n=750)
One Year follow-up for MACCE
Three Year follow-up for death/MI/CVA
ClinicalTrials.gov Identifier: NCT

13. FFR in Acute Coronary Syndromes
Comparison of MACE in FAME patients with and without ACS
Tonino, et al. J Am Coll Cardiol Intv 2011;4:

14. FFR in STEMI (Non-Culprit Vessels)
Ntalianis, et al. J Am Coll Cardiol Intv 2010;3:1274.
101 patients with an acute coronary syndrome (75 STEMI, 26 NSTEMI)
112 non culprit stenoses FFR measured acutely and 3524 days later
In only 2/112 stenoses was the FFR >0.80 during the ACS and <0.75 at follow-up.

15. FFR for Assessing Left Main Disease
FFR in 209 patients with intermediate LM disease followed for 5 years
Medical Therapy
Revascularization
Hamilos, et al. Circulation 2009;120:1505

16. Left Main Stem Stenoses are Rarely Isolated
The influence of a distal stenosis
on the FFR of the LM depends
on the extent to which
hyperemic flow across the LM
stenosis will be decreased by this
distal lesion
Severity
Myocardial mass
Courtesy Bernard De Bruyne, MD, PhD

17. Left Main Stem Stenoses are Rarely Isolated
The influence of a distal stenosis
on the FFR of the LM depends
on the extent to which
hyperemic flow across the LM
stenosis will be decreased by this
distal lesion
Severity
Myocardial mass
Courtesy Bernard De Bruyne, MD, PhD

18. Left Main Stem Stenoses are Rarely Isolated
The influence of a distal stenosis
on the FFR of the LM depends
on the extent to which
hyperemic flow across the LM
stenosis will be decreased by this
distal lesion
Severity
Myocardial mass
Courtesy Bernard De Bruyne, MD, PhD

19. Effect of Downstream Stenosis on LM FFR:
Human Validation
Un-inflated balloon used to simulate LM stenosis
Balloons inflated within stent to simulate downstream stenosis
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2 pressure wires with sensors in the distal LAD and LCX
Yong, et al. JACC Intervent 2015; in press. 19 19

20. Effect of Downstream Stenosis on LM FFR:
Human Validation
91 paired measurements obtained in 25 patients
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To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
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Select the text at the bottom of the slide and type in a short version of your presentation title.
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Yong, et al. JACC Intervent 2015; in press. 20 20

21. Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI
FAME 2
Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI
N = 1220
FFR in all target lesions
Randomized Trial
73%
Registry
50% randomly
assigned to FU
27%
At least 1 stenosis
with FFR ≤ 0.80 (n=888)
Randomization 1:1
PCI + MT MT
When all FFR > 0.80
(n=332) MT
This slide shows the study design.
Patients scheduled for 1, 2 or 3 vessels DES PCI were included. The first step was measure FFR in all lesio,ns considered for stenting.
If at least one of these stenoses appeared to be hemodynmically significant stenosis as defined by an FFR lower than 0.80, only then the patient were randomized to receive PCI + medical therapy or med therapy alone.
In contrast patients in whom all stenoses appeared to be hemodynamically non significant were NOT randomized, were treated with the best available medical therapy and followed up in a registry.
Thus importnat to realize that in the FALME 2 study there is a randomized trial with patients with ischemia and a registry with patients without ischemia.
Primary Endpoint: Death, MI or Urgent Revascularization at 2 Yr

22. FAME 2: Two Year Follow-Up
51% of urgent revascularizations were triggered by myocardial infarction or ischemic ECG changes (3.4 vs 7.0%, p=0.01, PCI vs OMT)
>80% of urgent revascularizations were triggered by myocardial infarction, ischemic ECG changes, or Class IV angina
De Bruyne, et al. NEJM 2014;371:

23. FAME 2: Two Year Follow-Up
Landmark Analysis of Death/MI after 7 days
4.6 vs. 8.0%, p=0.04 5 10 15 20
Cumulative incidence (%) 2 4 6 8 12 14 16 18 22 24
Months after randomisation .5 1
1.5
2.5 3 7
Days after randomisation
0-7days: HR 9.01 (95%CI )
8 days-2years: HR 0.56 (95%CI )
P for interaction 0.002
PCI+MT vs MT
PCI+MT
MT alone
De Bruyne, et al. NEJM 2014;371:

24. Spontaneous vs. Procedural MI
5 year F/U in 5,467 patients from RITA-3, ICTUS, and FRISC-II
Cumulative CV Death (%)
Spontaneous MI
22.2%
Procedural MI
5.2%
5 Years
Damman, et al. Circulation 2012;125:

25. FAME 2: Cost-Effectiveness
The Incremental Cost-Effectiveness Ratio was $36,000 per QALY
80% of the 10,000 replications were below the $50,000/QALY willingness-to-pay threshold and 99.5% were below the $100,000/QALY threshold
The difference in the primary endpoint in FAME 2 was driven by an increased rate of hospitalization requiring urgent revascularization and not due to a difference in death and MI. Because this may be considered a softer endpoint, it is critical to evaluate the cost-effectiveness of this approach. We found that patients treated with PCI not surprisingly, had higher up front costs, but there were significant improvements in quality of life as well as a narrowing of the cost difference over time as the medical therapy arm incurred higher event rates. This resulted in an attractive cost-effectiveness ratio of $36,000/QALY and with most of the bootstrap simulations falling under the $50,000/QALY threshold.
Circulation 2013;128:

26. When Shouldn’t We FFR?
Patient with typical angina and ischemia on non-invasive testing in a region supplied by a vessel with an angiographically significant lesion
Culprit vessel of a STEMI in the acute phase
If the FFR result is not going to change your treatment plan

27. How to perform FFR? Should we measure resting Pd/Pa and/or iFR?
How about “contrast” FFR (cFFR)?
New FFR devices
How do we deal with the “grey zone”?

28. Resting Pd/Pa and iFR versus FFR
Resting Pd/Pa , iFR and FFR were measured in 1,678 patients
Diagnostic Accuracy
of Resting Pd/Pa = 81.5%
Jeremias, et al. J Am Coll Cardiol 2014;63:

29. Resting Pd/Pa and iFR versus FFR
Resting Pd/Pa , iFR and FFR were measured in 1,678 patients
Diagnostic Accuracy
of iFR = 80.4%
Jeremias, et al. J Am Coll Cardiol 2014;63:

30. How about “contrast” FFR (cFFR)?
Resting Pd/Pa = 0.98 and iFR > 0.90 across a moderate circumflex lesion

31. How about “contrast” FFR (cFFR)?
cFFR = 0.79 (6 ml Isovue) across a moderate circumflex lesion

32. How about “contrast” FFR (cFFR)?
FFR = 0.77 (240 mcg IC Adenosine) across a moderate circumflex lesion

33. CONTRAST Study:
Comparison of FFR with IV or IC adenosine to: cFFR, Resting Pd/Pa and iFR
Multicenter, international trial including ≈750 patients (1 lesion/patient)
Blinded, independent core lab
Results expected this Spring
ClinicalTrials.gov Identifier: NCT

34. New FFR Devices: Design Goals Integrated POLARIS display
Wireless from bed-to-POLARIS
Targeting improved wire performance
Workhorse-like feel
‟Invisible” connection
Accurate (no drift)
Reliable (re)connection
POLARIS Display
Wireless Bedside
Disposable Cable
FFR Wire
Courtesy: Boston Scientific

35. New FFR Devices:
Optowire
Optomonitor
Opsensmedical.com

36. New FFR Devices:
Acist.com

37. “Grey Zone”

38. FFR Meta-Analysis “Ischemia is not a dichotomous state,
but a graded continuum”
Johnson, et al. J Am Coll Cardiol 2014;64:

39. Conclusions:
Fractional flow reserve is an indispensable tool for guiding decisions regarding coronary revascularization which leads to better resource utilization and most importantly improved patient outcomes.