CFR, FFR, ifr: Theoretical Advantages and Practical Applicability

Transcription

1 New York, 19 June 2015 CFR, FFR, ifr: Theoretical Advantages and Practical Applicability Carlo Di Mario, Sukhjinder Nijjer, Justin Davies Royal Brompton Hospital & Imperial College, London, UK

2 Disclosures None

3 Lance Gould, Master of Coronary Physiology Circulation 1974 Circulation Research 1978

4 Coronary Flow Velocity Reserve PRO CFVR: HYPEREMIC FLOW BASELINE VELOCITY True measurements of flow changes and flow impairment through stenosis Validated against nuclear myocardial perfusion CONTRA Cumbersome to acquire stable velocity signal Reflects severity of epicardial stenosis and impairment of microcirculation

5 No PTCA N= 124 No PTCA N= 37 No PTCA N= 21 No PTCA N= 9 ILIAS, JACC (6%) 9 (24 %) 1 (5%) 1 (11%)

6 DEBATE STUDY (Doppler Endpoints Balloon angioplasty Trial Europe) 297 Patients with Doppler Measurements after PCI Percent incidence of recurrence of symptoms and/or ischemia, TLR, and angiographic restenosis in the four groups Serruys P, Di Mario C et al. Circulation 1997 Group I, n=44, DS 35% and CFR >2.5; Groups II+III+IV, n=158, DS >35% or CFR 2.5; Group II, n=60, DS >35% and CFR >2.5; group III, n=42, DS 35% and CFR 2.5; Group IV, n=56, DS >35% and CFR 2.5

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8 YEAR No. PTS TREATMENT PRIMARY END-POINT/ LONGEST F-UP DEFER out of 325 ENROLLED POBA/BMS (46%) vs FFR- GUIDED DEFERRAL 5 YEAR DEATH/MI/ALL REVASC. 27.3% POBA/BMS vs 21.2% DEFERRAL (P= 0.52) FAME out of 1220 ENROLLED OMT vs FFR GUIDED PCI (2nd Generation DES 88%) FAME ANGIO-GUIDED vs. FFR-GUIDED MV PCI (50.4 CYPHER/TAXUS; 44% ENDEAVOR 2 YEAR DEATH/MI/URGENT REVASC. 19.5% OMT v 8.1% FFR GUIDED PCI (P=0.001) 2 YEAR DEATH/MI/URGENT REVASC. 22.4% ANGIO-GUIDED vs 17.9% FFR- GUIDED (P=0.08) * * BUT DEATH/MI 8.4 vs.12.9, P= 0.02

9 FAME FAME

10 De Bruyne. Late Breaking Trials ESC 2014

11 2986 patients (n = 4086 coronary stenoses) were evaluated retrospectively Correlation between diameter stenosis vs. FFR in the overall population and specifically in the left main stem and the three major branches. The x-axes indicate the functional metric (FFR), and the y-axes indicate the angiographic metrics (DS). EHJ 2014

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

13 De Bruyne et al. NEJM 2014

14 Urgent revascularization was triggered 80% by an MI, by dynamic ST changes, by resting angina De Bruyne et al. NEJM 2014

15 De Bruyne et al. NEJM 2014

16 Pressure (mm Hg) ifr = instantaneous wave-free ratio Definition: Instantaneous pressure ratio across a stenosis during the wave-free period, when resistance is naturally constant and minimised in the cardiac cycle Wave-free period Pa Pd Time (ms) Sen S,..., Davies J: J Am Coll Cardiol 2012;59:

17 Wave Intensity Analysis Davies, Circulation 2006

18 ifr receives FDA approval March 2014

19 ADenosine Vasodilator Independent Stenosis Evaluation II - ADVISE II Design: Prospective, global (EMEA, NORAM), multicenter (n=45) registry Data collection: standardized guidewire/console, IV adenosine, mandatory pressure pullback. ifr algorithm: ifr calculation software analysis tool (HARVEST) identical to online commercial system. ifr calculation and data analysis: performed at an independent core laboratory (CARDIALYSIS, Rotterdam, The Netherlands). The primary endpoint is focused on the clinical applicability of ifr in the context of a hybrid ifr/ffr strategy 1. Escaned J, EuroPCR 2013 Flow chart Coronary stenosis inclusion / exclusion criteria met Online FFR at cath lab FFR-based decision making Off line analysis of recordings at core lab Calculation of ifr (blind) and FFR Primary / Secondary endpoints

20 ADenosine Vasodilator Independent Stenosis Evaluation II - ADVISE II Pre-specified interim analysis at n=300 n=308 patients, 354 stenoses 203 stenoses ifr 0.85 or 0.94 ( , ) 81 stenoses ifr 0.85 to ifr/ffr stenoses included in results 70 tracings rejected by core lab* *Artifacts in pressure or ECG recording: 37; pressure drift documented: 19; pullback not recorded: 7; other: 7 Escaned J, EuroPCR 2013

21 300 Patients: Prespecified Interim Analysis Scatterplot of ifr and FFR Pearson s correlation coefficient: 0.741, 95% CI ( ), p< Reference lines are for ifr=0.86 and 0.93 and for FFR=0.80. Escaned J, EuroPCR 2013

22 300 Patients: Prespecified Interim Analysis Primary endpoint Stenoses properly classified by ifr in terms of hemodynamic severity (outside 0.85 or ifr 0.94): 88.2% [95% CI: 82.9, 92.3] % 86.2 % 95% CI [75.3, 93.5] 89.1% 95% CI [82.9, 92.3] Escaned J, EuroPCR 2013

23 Petraco R, van de Hoef TP, Nijjer S, Sen S, van Lavieren MA, Foale RA, et al. Baseline instantaneous wave-free ratio as a pressure-only estimation of underlying coronary flow reserve: Results of the JUSTIFY-CFR Study (Joined Coronary Pressure and Flow Analysis to Determine Diagnostic Characteristics of Basal and Hyperemic Indices of Functional Lesion Severity- Coronary Flow Reserve). Circ Cardiovasc Interv 2014; 7: JUSTIFY-CFR

24 Functional Lesion Assessment of Intermediate stenosis to guide Revascularisation Intermediate lesion requiring physiological assessment In ACS : intermediate non-culprit lesion N=2500, 1:1 Randomisation FFR guided PCI ifr guided PCI FFR>0.8 Defer PCI FFR 0.8 Perform PCI ifr 0.9 Defer PCI ifr<0.9 Perform PCI 30 day, 1, 2 and 5yr follow-up

25 69 years old gentleman with hypertension and hypercholesterolemia; minimal chest pain FFR pull-back before treatment

26 Stent to the distal lesion and FFR assessment

27 Distal FFR after OCT Optimised Stent Deployment to the Proximal and Distal lesion 4 FFR pull-backs, 3 adenosine syringes changed Approx. 20 more minutes and significant extra-cost added

28 DISTAL vessel Proximal vessel

29 0.93 Proximal vessel

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31 CFR, FFR, ifr? Conclusions CFR started the adoption of functional indices of stenosis severity but it is dependent on microcirculatory changes and the proposed corrections with pressure/velocity indices are not practically applicable in a busy lab FFR is the approved gold standard and enjoys the back-up of outcome studies with clinically relevant improvements in hard-endpoints ifr has the potential to simplify acquisition, boosting clinical applicability especially in complex serial lesions, possibly with no or better correlation with clinical endpoints