1. Journal : Evidence Review PCI : Role of FFR Dr Binjo J Vazhappilly SR Cardiology MCH Calicut

2. FFR is defined as the ratio of flow in stenotic artery to flow in same artery in the absence of stenosis. FFR is calculated as the ratio of mean pressure distal (Pd) to stenosis to Aortic pressure (Pa ), during maximal hyperemia.

3. Validation studies of FFR Author n Ischemic Test BCV Accuracy Pijls et al 60 X-ECG 0.74 97 DeBruyne et al. 60 X-ECG/SPECT 0.72 85 Pijls et al 45X-ECG/SPECT/DSE 0.75 93 Bartunek et al 37 DSE 0.68 90 Abe et al 46 SPECT 0.75 91 Chamuleau et al 127 SPECT 0.74 77 Caymaz et al. 40 SPECT 0.76 95 Jimenez-Navarro et al 21 DSE 0.75 90 Usui et al 167 SPECT 0.75 79 Yanagisawa et al 167 SPECT 0.75 76 Meuwissen et al 151 SPECT 0.74 85 DeBruyne et al 57 MIBI-SPECT post-MI 0.78 85 Samady et al 48 MIBI-SPECT post-MI 0.78 85 JACC Vol. 55, No. 3, 2010

4. 2011 ACC/AHA/SCAI Guideline for PCI Class II a FFR is reasonable to assess angiographic intermediate coronary lesions (50% to 70% diameter stenosis) and can be useful for guiding revascularization decisions in patients with Stable IHD.

5. FFR in SCAD : 2013 ESC guidelines

6. DEFER study Aim : To investigate whether FFR discriminates pts in whom PTCA is appropriate among pts referred for PTCA, without documented ischemia. Primary end point : Absence of adverse cardiac events ( all-cause mortality, MI, CABG, coronary angioplasty), during 24 months of follow-up. Study done in multiple centers in Netherlands, Spain, Belgium, Germany, South korea, Japan. 5 year follow-up also done. Circulation 2001;103:2928-2934 G. Jan Willem Bech, MD; Bernard De Bruyne, MD, PhD; Nico H.J. Pijls MD et al

7. DEFER Group REFERENCE Group PERFORM Group DEFER Study: Flow Chart Patients scheduled for PCI without Proof of Ischemia (n=325) Performance of PTCA (158) Deferral of PTCA (167) FFR  0.75 (91) No PTCA FFR  0.75 (90) PTCA FFR < 0.75 (76) PTCA FFR < 0.75 (68) PTCA Randomization

8. Event Free survival : 2Yrs Circulation 2001;103

9. Free from angina Circulation 2001;103

10. No. at risk Defer group90 85 82 74 73 72 Perform group88 78 73 70 67 65 Reference gr135 105 103 96 90 88 78.8 72.7 64.4 012345 0 25 50 75 100 Defer Perform Reference (FFR < 0.75) p=0.52 p=0.17 p=0.03 Years of Follow-up Event free survival (%) : 5 Yrs JACC Vol. 49, No. 21, 2007

11. 0% 20% 40% 60% 80% 100% baseline1month1 year2 year5 year Defer groupPerform groupReference group Freedom from chest pain FFR > 0.75 FFR > 0.75 FFR < 0.75 * * *** JACC Vol. 49, No. 21, 2007 *p 0.028 **p <0.001 ***p 0.021

12. Cumulative Events After 5 Yrs

13. DEFER study conclusions Compared with medical treatment, PTCA in pts with FFR > 0.75 did not reduce adverse cardiac events or improvement in functional class. In pts with FFR < 0.75, PTCA resulted in significant improvement in functional class. Lesions at greatest risk of causing cardiac death or AMI are those that are functionally significant ( FFR < 0.75) and risk persists even after PCI.

14. Outcomes after FFR based deferral of coronary intervention in intermediate coronary lesions Author n Defer value MACE(%) Follow up (months) Hernandez Garcia et al 43 0.75 12 11 Bech et al 60 0.75 12 24 Rieber et al 47 0.75 13 12 Chamuleau et al 92 0.75 9 12 Rieber et al 24 0.75 8 12 Leesar et al 34 0.75 9 12 Bech et al 100 0.75 8 18

15. FAME (FFR Vs Angiography for Multivessel Evaluation) Study In the FAME Study, 1005 patients with multivessel CAD were randomly assigned to FFR-guided PCI or angiography-guided PCI with DES and followed for one year. Primary end point was rate of major adverse cardiac events at 1 yr : composite of death, MI and repeat revascularization. Randomised multicenter study in 20 US and European centers. n engl j med 360;3 january 15, 2009

16. Angiography-guided PCI FFR-guided PCI Stent all indicated stenoses Stent only those stenoses with FFR ≤ 0.80 Randomization Indicate all lesions ≥ 50% amenable for stenting Patient with lesions ≥ 50% in at least 2 of the 3 major epicardial vessels 1-year follow-up FAME Study Design Exclusion criteria: LM disease, Previous CABG MI < 5 days Pregnancy, Life expectancy < 2 years n engl j med 360;3 january 15, 2009 496 pts509 pts

17. ANGIO- group N=496 FFR-group N=509P-value Indicated lesions per patient 2.7 ± 0.92.8 ± 1.00.34 FFR results Lesions succesfully measured, No (%) -1329 (98%)- Lesions with FFR ≤ 0.80, No (%) -874 (63%)- Lesions with FFR > 0.80, No (%) -513 (37%)- Stents per patient 2.7 ± 1.21.9 ± 1.3<0.001 Lesions succesfully stented (%) 92%94%- DES, total, No 1359980- FAME study: Procedural Results

18. ANGIO- group N=496 FFR-group N=509 P-value Events at 1 year, No (%) Death, MI, CABG or repeat-PCI91 (18.4)67 (13.2)0.02 Death15 (3.0)9 (1.8)0.19 Death or myocardial infarction55 (11.1)37 (7.3)0.04 CABG or repeat PCI47 (9.5)33 (6.5)0.08 Total no. of MACE 113760.02 Myocardial infarction, specified All myocardial infarctions43 (8.7)29 (5.7)0.07 FAME study: Adverse Events at 1 year

19. FFR-guided 30 days 2.9% 90 days 3.8% 180 days 4.9% 360 days 5.3% Angio-guided absolute difference in MACE-free survival FAME study: Event-free Survival

20. End points at 2 years JACC :Vol. 56, No. 3, 2010

21. FAME 2 Aim: To compare clinical outcomes of FFR- guided contemporary PCI plus best available medical therapy (MT) versus MT alone in patients with stable CAD. Primary end points : Composite of all cause death,MI, unplanned hospitalization with urgent revascularization. The trial was conducted at 28 sites in Europe and North America.

22. Patient recruitment was stopped on January 15, 2012, owing to a highly significant difference in incidence rates of primary end point between the PCI and medical- therapy groups. Between May 15, 2010 and January 15, 2012, a total of 1220 patients were enrolled in the study.

23. Flow Chart Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI N = 1220 FFR in all target lesions When all FFR > 0.80 (n=332) MT At least 1 stenosis with FFR ≤ 0.80 (n=888) Randomization 1:1 PCI + MT MT Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years Registry 50% randomly assigned to FU 27% FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Randomized Trial 73%

24. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Primary Outcomes 0 5 10 15 20 25 30 Cumulative incidence (%) 16615614513311710693746452412513Registry 4474143883513082772432121751551179253PCI+MT 4414143703222832532201921621271007037MT No. at risk 0123456789101112 Months after randomization MT vs. Registry: HR 4.32 (1.75-10.7); p<0.001 PCI+MT vs. Registry: HR 1.29 (0.49-3.39); p=0.61 PCI+MT vs. MT: HR 0.32 (0.19-0.53); p<0.001

25. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Death from any Cause 0 5 10 15 20 25 30 Cumulative incidence (%) 16615614513411810796766755432713Registry 4474233963593182882502201831631229554PCI+MT 4414233903503122812472191881541229054MT No. at risk 0123456789101112 Months after randomization MT vs. Registry: HR 2.66 (0.14-51.18); p=0.30 PCI+MT vs. Registry:HR 1.12 (0.05-27.33); p=0.54 PCI+MT vs. MT: HR 0.33 (0.03-3.17); p=0.31

26. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Myocardial Infarction 0 5 10 15 20 25 30 Cumulative incidence (%) 16615614513411810795756553422613Registry 4474143883523092782442141771571199454PCI+MT 4414213863413042732392121821481178548MT No. at risk 0123456789101112 Months after randomization MT vs. Registry: HR 1.65 (0.50-5.47); p=0.41 PCI+MT vs. Registry:HR 1.61 (0.48-5.37); p=0.41 PCI+MT vs. MT: HR 1.05 (0.51-2.19); p=0.89

27. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Urgent Revascularization 0 5 10 15 20 25 30 Cumulative incidence (%) 16615614513311710694756553422613Registry 4474213953563152852482171801601199353PCI+MT 4414143713252862562231951641291017138MT No. at risk 0123456789101112 Months after randomization MT vs. Registry: HR 4.65 (1.72-12.62); p=0.009 PCI+MT vs. Registry: HR 0.63 (0.19-2.03); p=0.43 PCI+MT vs. MT: HR 0.13 (0.06-0.30); p<0.001

28. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Patients with urgent revascularization Myocardial Infarction Unstable angina +evidence of ischemia on ECG 51.8% 26.8% 21.4%

29. 020406080 Percentage of patients with CCS II to IV, % Baseline 30 days 6 months 12 months PCI+MT MT Registry PCI+MT MT Registry PCI+MT MT Registry PCI+MT MT Registry FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Patients with Angina Class II to IV P<0.001 P=0.002 P=0.073 P=0.002

30. Conclusions FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD In patients with stable coronary artery disease, FFR-guided PCI, improve patient outcome as compared with medical therapy alone. This improvement is driven by a dramatic decrease in the need for urgent revascularization for ACS. In patients with functionally non-significant stenoses medical therapy alone resulted in an excellent outcome, regardless of the angiographic appearance of the stenoses.

31. Value of FFR in making decisions about bypass surgery for equivocal LMCA disease. Was a 2 centre prospective, single cohort follow up study. FFR of LMCA was determined in 54 consecutive pts with angiographically equivocal disease. If FFR was > 0.75, medical treatment was chosen and if FFR was < 0.75, surgical treatment was chosen. Heart 2001; 86:547–552G J W Bech, H Droste, N H J Pijls et al

32. In 24 pts (44%), FFR was > 0.75 and medical treatment was chosen & in 30 pts (56%), FFR was < 0.75 and bypass surgery was performed. Survival among pts at 3 yrs of follow up was 100% in medical group and 97% in surgical gp. Event-free survival was 76% in medical gp and 83% in surgical gp. Heart 2001; 86:547–552G J W Bech, H Droste, N H J Pijls et al

33. Long-Term Outcome After FFR Guided Treatment in Patients With Angiographically Equivocal LMCA Stenosis 213 pts with an angiographically equivocal LMCA stenosis, FFR measurements were performed. If FFR was ≥ 0.80, patients were treated medically or another stenosis was treated by coronary angioplasty ( n 138). When FFR was < 0.80, CABG was performed (n 75). 5-year survival estimates were 89.8% in nonsurgical gp and 85.4% in surgical gp (P = 0.48). The 5-year event-free survival estimates were 74.2% and 82.8% in the nonsurgical and surgical groups, respectively (P = 0.50) Circulation. 2009;120:1505-1512, Michalis Hamilos, Olivier Muller et al

34. FFR for assessment of Nonculprit coronary artery stenoses in patients with Acute MI. Aim : To investigate reliability of FFR of nonculprit coronary stenoses during PCI in acute MI. 101 pts undergoing PCI for acute MI were prospectively recruited. The FFR measurements in 112 nonculprit stenoses were obtained immediately after PCI of the culprit stenosis and were repeated 35 ± 4 days later. The FFR value of nonculprit stenoses did not change between the acute and follow-up (0.77 ± 0.13 vs 0.77 ± 0.13, respectively, p NS). JACC : V O L. 3, N O. 1 2, 2 0 1 0Argyrios Ntalianis, Jan-Willem Sels et al

35. Physiological evaluation of provisional side-branch intervention for bifurcation lesions using FFR Aim : To evaluate functional outcomes of FFR -guided jailed sidebranch (SB) intervention strategy. 110 pts were consecutively enrolled and SB FFR was measured in 91 pts. SB intervention was allowed when FFR was < 0.75. FFR measurement was repeated after SB intervention and at 6- month follow-up angiography European Heart Journal (2008) 29, 726–732 Koo, Park et al

36. In 26 of 28 SB lesions with FFR < 0.75, balloon angioplasty was performed and FFR 0.75 was achieved in 92% of the lesions. During follow-up, there were no changes in SB FFR in lesions with (0.86 ± 0.05 to 0.84 ± 0.01, P = 0.4) and without SB angioplasty (0.87±0.06 to 0.89 ± 0.07, P = 0.1). Functional restenosis (FFR,0.75) rate was only 8% (5/65). European Heart Journal (2008) 29, 726–732 Koo, Park et al

37. Clinical outcomes of were compared with 110 pts with similar bifurcation lesions treated without FFR-guidance, there was no difference in 9-month cardiac event rates (4.6 vs. 3.7%, P = 0.7) between two gps. Cardiac events were defined as cardiac death, myocardial infarction, or target vessel revascularization European Heart Journal (2008) 29, 726–732 Koo, Park et al

38. Summary FFR is useful to assess angiographic intermediate coronary lesions and can guide revascularization decisions in pts with stable IHD. Medical therapy is appropriate when FFR ≥ 0.8. Revascularization is recommended in lesions where FFR < 0.8 and patient having evidence for ischemia. FFR is helpful in making decision in intermediate LMCA disease. FFR can assess nonculprit lesions during ACS. FFR is useful in intervention of bifurcation lesions.