FFR DECISION MAKING DURING DIAGNOSTIC PROCEDURES CRT 2017 Clinical Outcomes: FFR, iFR, IMR, CFR Feb 18, 2017 Habib Samady MD FACC FSCAI Professor of Medicine Director, Interventional Cardiology, Emory University Director, Cardiac Catheterization Laboratory, Emory University Hospital

Disclosures Grant Support • Medtronic, PI SHEAR STENT Trial • Abbott Vascular, PI Restoration Study • Gilead, PI MARINA TrialInc. • Volcano Therapeutics, Research Grants and Steering Comm ADVISE II • St. Jude Medical, Research Grants and Advisory Board Intravasc. OCT • Toshiba, PI Angiographic vs IVUS WSS Evaluation • Forrest Pharmaceuticals, PI Nebivolol vs Atenolol study • American Heart Association, Mentor Fellowship Awards • National Institute of Health, Co-I NIH ROI/PPG • American College of Cardiology, Deputy Editor, JACC Interventions

Survival Benefit with Revascularization Stratified by Ischemic Risk N=10 627 undergoing MPI with 1.9±0.6 year f/u propensity matched. P <.0001 Cardiac Death Rate 1331 56 718 109 545 243 252 267 1- 5% 5-10% 11-20% >20% % Total Myocardium Ischemic Hachamovitch et al Circulation. 2003; 107:2900-2907

SPECT MPI Does Not Localize Regional Ischemia in Severe Multivessel Disease Lima..Samady JACC, 2003;42:64-70 N=143 pts, with severe 3 VD who underwent Gated SPECT with 1 month Finally, assessment of patients with multi-vessel coronary disease can be quite challenging. Non-invasive tests, particularly nuclear perfusion scans, performed prior to coronary angiography may not be helpful in guiding revascularization decisions. In fact, in a study done recently at UVA comparing the findings on stress perfusion imaging with angiography, almost 20% of patients with severe three vessel disease on angiography had normal stress perfusion scans and 36% had perfusion defects in only one vascular territory. The likely explanation for this finding relates to the fact that nuclear perfusion imaging is based on the demonstration of differences in tracer uptake in one zone compared to another. If there is significant stenoses affecting all vascular beds, there may not be a relative difference in tracer uptake evident. Thus, in the presence of multi-vessel coronary disease, the nuclear scan is unlikely to help determine the physiologic significance of a stenosis. In these cases, interrogation of each vessel with FFR will likely provide much more useful information.

Complexity of Angiographic Lesion Assessment Entrance effects Separation losses Friction loss Kern and Samady. JACC 2010;55:173-185

Fractional Flow Reserve Pa Pd Fractional flow reserve is the ratio of maximal myocardial perfusion in the stenotic territory divided by maximal hyperemic flow in that same region but in the hypothetical case the lesion were absent. Stated another way, FFR represents that very fraction of hyperemic flow that still persists despite the presence of the stenosis. It has been demonstrated that the this ratio of two flows could be calculated solely from the ratio of mean coronary pressure divided by mean aortic pressure provided both pressure are recorded under conditions of maximal hyperemia. NHJ Pijls et al. Circulation 1993 6

Validation of FFR For Intermediate Lesion Assessment Kern and Samady. JACC 2010;55:173-185

FAME Study: One Year Outcomes p=0.02 p=0.04 % ~40%  ~35%  ~30%  New Engl J Med 2009;360:213-24.

FAME Fearon. JACC. 2010 Fearon. Circulation. 2010; 122: 2545-2550 FFR-Guided Angio-Guided 720 days 4.5% Fearon. Circulation. 2010; 122: 2545-2550 Fearon. JACC. 2010 9

Relationship Between FFR and Outcomes FAME 2: Patients with angiographically significant stenoses treated with OMT Event Rates (%) 4.3 FFR Stenosis Severity (FFR) Courtesy of: Bernard De Bruyne, MD, PhD

Functional Syntax Score Without FFR Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8

Functional Syntax Score Reclassifies > 30% of cases Without FFR With FFR Without FFR Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8 Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8

Functional Syntax Score 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

What Diameter Stenosis Requires Physiologic Interrogation? 20% 35% 96% Tonino. JACC 2010; 55(25):2816-21

Routine Incorporation of FFR in Real Practice IVUS use FFR was measured 1267 patients (1551 lesions) FFR use Seung-Jung Park et al. EHJ 2013

Seung-Jung Park et al. EHJ 2013 Simplifying Multi-vessel Disease Before and After Implementation of Routine FFR Seung-Jung Park et al. EHJ 2013

Seung-Jung Park et al. EHJ 2013 Simplifying Multi-vessel Disease Before and After Implementation of Routine FFR Rate of Fractional Flow Reserve (FFR) Use between 2008 and 2011. Since January 2010, FFR has been routinely used during PCI. Shown is the quarterly rate of FFR use, which was between 0% and 13% before the routine use of FFR and between 38% and 58% after the introduction of the routine use of FFR. During the study period, the rate of intravascular ultrasound (IVUS) use was over 80%. The FFR use is shown in blue, and IVUS use is red. Seung-Jung Park et al. EHJ 2013

Rationale for FAME 3 % 20 1 year MACE Rates 10 PCI - angio PCI PCI - FFR 18.4 13.2 FAME 20 10 % SYNTAX PCI CABG 19.1 11.2 1 year MACE Rates

FAME 3 Trial: Study Flow All Comers with 3 V CAD (Excluding LMD) Heart team identifies lesions for PCI/CABG and then patient is randomized FFR-Guided PCI with Resolute DES Stent all lesions with FFR ≤ 0.80 (n=750) Perform CABG based on coronary angiogram (n=750) Primary: One Year follow-up for Death, MI, CVA, Revascularization Key Secondary: Three Year follow-up for Death/MI/CVA Non-inferior Design

MODIFIED Recommendation NCDR PCI Registry Quality Indicator: FFR It is reasonable to use intracoronary physiologic measurements (coronary pressure [FFR])(Level of Evidence: A) in the assessment of the effects of intermediate coronary stenoses (30% to 70% luminal narrowing) in patients with anginal symptoms. MODIFIED Recommendation I IIa IIb III A ESC/ACC/AHA PCI Guidelines: FFR NCDR PCI Registry Quality Indicator: FFR 31

FFR DECISION MAKING DURING DIAGNOSTIC PROCEDURES CRT 2017 Clinical Outcomes: FFR, iFR, IMR, CFR Feb 18, 2017 Habib Samady MD FACC FSCAI Professor of Medicine Director, Interventional Cardiology, Emory University Director, Cardiac Catheterization Laboratory, Emory University Hospital