1) A study evaluated the impact of incorporating FFRCT data with CT angiogram results compared to CT angiogram alone in 200 patients. 2) The addition of FFRCT data led to a change in management in 36% of cases, similar to prior studies using invasive FFR. 3) This suggests non-invasive FFRCT can mimic invasive FFR's ability to refine management decisions made based on angiography alone. A definitive randomized trial is now needed to establish FFRCT's role as a default screening test for patients with chest pain.

1. Nick Curzen BM(Hons) PhD FRCP
Professor of Interventional Cardiology
University Hospital Southampton NHS FT
3 October 2016
FFRCT : the future is now

2. Potential conflicts of interest
Honorarium:
HeartFlow, St Jude Medical, Haemonetics, Boston Scientific
Lilly DS,
Institutional grant/research support:
Boston Scientific, Haemonetics, HeartFlow, Medtronic
03/10/2016
The FFRCT RIPCORD Study

3. 3 October 2016
 In patients with cardiac CP, knowing the coronary anatomy is useful
 However, the target for revascularisation is patient-level and lesion-specific ischaemia
 Multiple studies have shown a consistent modifying effect on angio-guided management
when invasive FFR data is available
 Despite these data, penetration of use of invasive FFR is low…
 CT angiography is increasingly accurate as an anatomical test
 Recent development of FFRCT allows for derivation of FFR from CT angio data
 Diagnostic accuracy of FFRCT is established
 PLATFORM demonstrated a large decrease in invasive angiography and reduction in angio
showing unobstructed coros in the cohort destined for invasive angio who actually had FFRCT…
 and this was associated with significantly lower resource utilisation
What we know so far….

4. 3 October 2016
What we need to know….
 Does it work?
 Does it affect decision-making and management in a similar way to invasive FFR?
 Are there any clinical outcome data?

5. 3 October 2016
JACC Imaging 2016

6. Background
•Invasive fractional flow reserve (FFR) is a well validated & reproducible tool
for detection of lesion-level ischaemia. 1
•In patients with multivessel disease an FFR-directed PCI strategy is associated with
better clinical outcomes compared to angiography-directed PCI (FAME; FAME 2) 1,2
•In RIPCORD, when invasive FFR was available, management was altered in 26% of cases
when compared to angiographic assessment alone because of a mismatch between
angio- & FFR-derived analyses of lesion “significance” 3
•Computed tomography (CT)-derived fractional flow reserve (FFRCT) is a novel diagnostic
technique that allows derivation of FFR from raw data acquired during CT coronary
angiography4
•Previous studies have demonstrated excellent diagnostic accuracy for this test
•As yet, however, there are no data to compare the management of patients with
stable angina using CT angiography alone versus angiography with FFRCT
1. Expert Rev Cardiovasc Ther 2013;11:1051-9
2. JACC 2014;64:1641-54
3. Circulation: Cardiovascular Interventions 2014;7:248-55.
4. Nature Reviews Cardiol 2014, 11: 252
The FFRCT RIPCORD Study
03/10/2016

7. Toth et al EHJ 2014Curzen et al Circ Interven 2014
Tonino et al JACC 2010
3-Oct-16
Berry et al Eur Heart J 2014

8. Hypothesis: Proof of Concept
In the assessment of patients with stable chest pain, the availability of
non-invasive FFRCT in addition to coronary anatomy from the CT angiogram:
(1) would lead to a substantial change in the interpretation of lesion-specific
“significance”
(2) that this would consequently lead to a change in the management plan
in a manner similar to that seen in RIPCORD.
The FFRCT RIPCORD Study
03/10/2016

9. The difference between the management based upon
interpretation of the CT angiogram alone compared to the
management incorporating the non-invasive FFRCT data.
Primary Endpoint
1. The correlation between vessels labelled as “significant” based
upon interpretation of the CT angiogram alone versus when FFRCT
data are available
2. Comparison between individual coronary arteries labelled as
targets for revascularisation based upon the CT angiogram alone
compared to FFRCT
Secondary Endpoints
The FFRCT RIPCORD Study
03/10/2016

10. 03/10/2016
Circ Cardiovasc Imaging 2013

11. 03/10/2016
• N=254
• CTA + FFRCT versus CTA alone per patient & per vessel using FFR <0.8
in vessels with lesions 30-90% as the reference
JACC 2014

12. Methods
• Three experienced interventional cardiologists (ICs) reviewed 200
consecutive cases of stable angina recruited into the NXT study of FFRCT. 5
• In each case the ICs reviewed the CT angiogram in detail, reported the
degree of stenosis(es) in the coronaries and then, by consensus, came to a
plan of management based upon the anatomic appearances, using 4
options:
(1) Optimal medical therapy (OMT); (2) PCI + OMT; (3) CABG + OMT; (4)
more information required (ie meaning invasive FFR needed)
• FFRCT data for each case was then revealed, and the ICs then asked to again
describe (a) which vessels were significant & (b) make a second
management plan based upon these data
5. JACC 2014; 63: 1145
The FFRCT RIPCORD Study
03/10/2016

13. Results 1
The FFRCT RIPCORD Study
03/10/2016
Degree of angiographic stenosis on CT versus FFRCT >/<0.8

14. Results 2
Overall there was a change in management in 72 (36%) of cases
P<0.001 by Chi-squared test
CT Angio Alone With FFRCT % change
More data 38 (19.0 %) 0 -
OMT 67 (33.5 %) 113 (56.5 %) + 23 %
PCI 87 (43.5 %) 78 (39.0 %) - 5%
CABG 8 (4.0 %) 9 (4.5 %) + 0.5 %
Management options chosen based upon CT angio alone and after FFRCT data revealed
n=200
The FFRCT RIPCORD Study
03/10/2016

15. Results 3
Detailed description of change in CTA-directed management after FFRCT revealed
19.0%
33.5%
43.5%
4.0%
56.5%
39.0%
4.5%
03/10/2016
The FFRCT RIPCORD Study
n= 200 cases
8 of 67 (12%) OMT patients
required revasc
26 of 87 (30%) PCI patients
required OMT only
16 of 87 (18%) PCI patients
the target vessel(s) changed
10 of 38 (26%) “more info”
patients required revasc

16. More information needed
N=38
Initial Decision – CT Angio only
Optimal Medical Therapy (OMT)
N=67
Intervention (PCI or CABG)
N=95
More information needed
N=0
Final Decision – Post FFRCT
Optimal Medical Therapy (OMT)
N=113 (68.7% increase)
Intervention (PCI or CABG)
N=87 (8.4% decrease)
Change in disease
management
pathway for
36% of patients
Change in vessel
assigned to PCI for
an additional
8% of patients
(18% of the PCI
Group after CTA)
44% of patients
had decisions altered
after physicians
incorporated FFRCT
n=200
University Hospitals Harrington Heart & Vascular Institute 16
Results 4 The FFRCT RIPCORD Study

17. CONCLUSIONS
• This study demonstrates a mismatch between CT angiographic assessment of lesion severity
& the FFRCT-derived estimate of ischaemia
• The addition of FFRCT data to CT angiography alone led to a change in management in 36%
of cases in this study
• These results are consistent with those of the invasive RIPCORD study
• If this novel proof of concept result can be confirmed in large scale trials, this suggests that
non-invasive FFRCT can be used as a clinically relevant tool that mimics the well-described
ability of invasive FFR to refine management decisions for patients with chest pain
that are made based upon ICA alone.
• This would have important implications for routine clinical practice.
• FFRCT may have potential as a default method for assessment of coronary anatomy and
physiology in angina patients in order to define their management
The FFRCT RIPCORD Study
03/10/2016

18. The FFRCT RIPCORD Study
03/10/2016
So …. How does this compare with the effect of invasive FFR when available with invasive angiography?

19. 3-Oct-163 October 2016
Study Year
No.
Patients Setting
FFR
Limit Stenosis Limit
Change in
management
Lesion
Change
Sant'Anna et al 2007 250 Elective 0.75 >50% 48% 32%
RIPCORD 2014 200 Elective 0.8 >30% 26% 32%
CVIT-DEFER Registry 2014 3093 Elective & ACS 0.8 50-90% 39%
FAMOUS 2014 350 ACS 0.8 >30% 22%
FFR-R3F 2014 1075 Elective & ACS 0.8 35-65% 43%
POST-IT 2016 918 Elective & ACS 0.75-0.8 Intermediate 44% 45%
Danish Registry 2016 1,716 Elective 0.8 50-89% 31% 48%
FFRCT RIPCORD 2016 200 Elective 0.8 >30% 36%
Studies reporting additive effect on patient management of adding FFR to angio alone

20. 3 October 2016

21. 3 October 2016

22. 3 October 2016
We now need a definitive randomised trial of the role of FFRCT as the
default screening test for patients who present with CP

23. 3 October 2016

24. 3 October 2016
Potential uses of FFRCT-type technology…..
 One stop assessment of patients presenting with CP
 Routine follow up post PCI/MI…. CABG….
 Screening populations for risk: diabetics… COPD…. Renal …. Rheumatoid… etc etc

25. 3 October 2016