Physiology in ISR and SVG Is there a

Physiology in ISR and SVG Is there a role for FFR assessment? Nils Johnson MD, MS, FACC, FESC Associate Professor of Medicine Weatherhead Distinguished Chair of Heart Disease Division of Cardiology, Department of Medicine and the Weatherhead PET Imaging Center Mc. Govern Medical School at UTHealth (Houston) Memorial Hermann Hospital – Texas Medical Center United States of America Weatherhead PET Imaging Center

Disclosure Statement of Financial Interest Within the past 12+ months, Nils Johnson has had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship • Grant/research support (to institution ) • Licensing and associated consulting (to institution ) • Support for educational Organizations (alphabetical) • St Jude Medical (for CONTRAST study) • Volcano/Philips (for DEFINE-FLOW study) • Boston Scientific (for smart-minimum FFR algorithm) meetings/training (honoraria/fees donated to institution ) • Various, including academic and • PET software 510(k) from FDA • K 113754 (cfr. Quant, 2011) • K 143664 (Heart. See, 2014) • K 171303 (Heart. See update, 2017) (application by Lance Gould, to institution ) • Patent pending (USPTO serial number 62/597, 134) industry • SAVI and ∆P/Q methods

Minority of FFR for ISR or grafts • Frequency in large FFR meta-analysis o 7000 to 9000 lesions o grafts = 1% of FFR’s o ISR = 5 -20% of FFR’s • Exclusion criterion for RCT’s o CABG = DEFER, FAME 1+2, FLAIR o ISR = DEFER, FLAIR Johnson NP, JACC. 2014 Oct 21; 64(16): 1641 -54. (Portions of Table 1)

FFR in ISR = no differences! upper, left = Nam CW, Am J Cardiol. 2011 Jun 15; 107(12): 1783 -6. (Figure 1) upper, right = Lopez-Palop R, EHJ. 2004 Nov; 25(22): 2040 -7. (Figure 1, bottom) lower, left = Yamashita J, Circ J. 2013; 77(5): 1180 -5. (Figure 3)

FFR in ISR = no differences! 50 lesions due to ISR of DES multicenter Korean cohort FFR<0. 8 received PCI FFR≥ 0. 8 treated medically Nam CW, Am J Cardiol … and ISR lesions were included in FAME 1 (27%) and in FAME 2 (18%) . 2011 Jun 15; 107(12): 1783 -6. (Figures 2 and 3) plus Table 1 of FAME’s

Not discussed in this talk … FFR to guide CABG (n=876) • FARGO (NCT 02477371), n=168 • GRAFFITI (NCT 01810224), n=206 • SAVE-IT (NCT 02173860), n=502 (main endpoint = graft patency) FFR-guided PCI vs CABG • FAME 3 (NCT 02100722), n=1500 (non-inferiority for composite MACCE)

FFR after CABG = open or closed? native closed = FFR “as usual” Di Serafino L, Am Heart J. 2013 Jul; 166(1): 110 -8. (Figure 1 B)

Native closed = FFR “as usual” Pellicano M, EHJ. 2017 Jul 1; 38(25): 1959 -1968. (Figure 5)

FFR after CABG = open or closed? native open = FFR “combination” Di Serafino L, Am Heart J. 2013 Jul; 166(1): 110 -8. (Figure 1 A)

Native open = combined effect Corban MT, Catheter Cardiovasc Interv . 2013 Jun 1; 81(7): 1169 -73. (Figure 5)

Pressure loss along graft itself ü ü FFR Glineur D, Eur J Cardiothorac Surg LIMA = 0. 90 FFR RIMA = 0. 95 . 2007 Mar; 31(3): 376 -81. (Figure 3 with 29 subjects, 43 grafts 6 -8 months after CABG no symptoms normal exercise test FFR SVG = 0. 96 annotations , some from

“FAME 1” for CABG patients FFR-guided angio-guided p=0. 003 • • Di Serafino L, FFR-guided p=0. 11 223 subjects with CABG stable or unstable angina retrospective, not randomized median 3. 8 years follow-up Am Heart J. 2013 Jul; 166(1): 110 -8. (Figure 3 [top row] and 2 [bottom right] with FFR-guided angio-guided p=0. 002

FFR for ISR and after CABG FFR for ISR • about 20% of FFR’s • part of large RCT’s • not different than usual FFR after CABG • about 1% of FFR’s • excluded from many RCT’s • likely same clinical benefit • some gradient due to graft • native closed = “per routine” • native open = “combination”