Fractional Flow Reserve Μηράιεο Φακειόο, MD, PhD, FESC Πανεπιστημιακό Νοσοκομείο Ηρακλείοσ
Fractional Flow Reserve (FFR) Η ζηεθαληνγξαθία δε ιέεη πάληα ηελ αιήζεηα όζνλ αθνξά ζηε βαξύηεηα ηωλ ζηελώζεωλ Οη πεξηζζόηεξνη από ηνπο αζζελείο πνπ έξρνληαη ζην εξγαζηήξην δελ έρνπλ ππνβιεζεί ζε κε επεκβαηηθό έιεγρν πξηλ Υπάξρεη ζαθήο αλάγθε ελόο απινύ θαη αμηόπηζηνπ εξγαιείνπ πνπ λα εθηηκά ηελ ζεκαληηθόηεηα κηαο ζηέλωζεο ηελ ώξα ηεο ζηεθαληνγξαθίαο
Myocardial Fractional Flow Reserve: Definition Fractional Flow Reserve is a ratio FFR = Q s max max Q N maximal myocardial flow in the stenotic territory normal maximal myocardial flow FFR = extent (%) to which the epicardial stenosis limits maximal myocardial blood flow
Myocardial Fractional Flow Reserve: Definition S Q max N Q max = FFR P a P d P v (P d -P v ) / R myo P d -P v FFR = = = S N (P a -P v ) / R myo P a -P v P d P a
P a P d + = FFR
Threshold Values of FFR to Detect Significant Stenosis FFR non-signif. stenosis significant 1.0 0.80 0.75 0 FFR < 0.75 always ischaemia (specificity 100 %) FFR > 0.80 ischaemia very unlikely (sensitivity 90 %) Pijls et al, NEJM1996
Features of FFR Has a normal value = 1.0 for every patient and every artery Is not influenced by changing hemodynamic conditions Accounts for collaterals Is easy to measure (success rate 99 %) and extremely reproducible Pressure measurement has un unequaled spatial resolution
Practicalities when Measuring FFR Catheter Guiding catheter without side holes Anticoagulation Heparine, ACT at lest 250 sec Wires WaveWire, Volcano Inc PressureWire, St Jude Medical Hyperaemia Nitrates i.c. Adenosine i.v (140μg/kg/sec)/i.c. (40 μg)
FFR and Eyeballing Hamilos et al, submitted
FFR and QCA r =-0.51, p<0.001 Hamilos et al, submitted
FFR: Κιηληθέο Εθακνγέο
FFR for Intermediate Lesion Assessment: The DEFER study Patients scheduled for PCI without Proof of Ischemia (n=325) Randomization deferral of PTCA (167) performance of PTCA (158) FFR 0.75 (91) FFR < 0.75 (76) FFR < 0.75 (68) FFR 0.75 (90) No PTCA PTCA PTCA PTCA DEFER Group REFERENCE Group PERFORM Group Bech et al, Circulation 2001
FFR for Intermediate Lesion Assessment: The DEFER study FFR > 0.75 FFR > 0.75 Bech et al, Circulation 2001
Cardiac Death and Acute MI after 5 years 20 % 15 10 P=0.20 P< 0.03 7.9 P< 0.005 15.7 5 3.3 0 DEFER PERFORM REFERENCE FFR > 0.75 FFR < 0.75 Pijls et al, JACC 2007
DEFER: Summary and Conclusions The most important prognostic factor of a stenosis, is its ability of inducing myocardial ischaemia In patients with an FFR < 0.75 incidence of AMI or death is 5 x higher than in a stenosis not associated with inducible ischaemia The prognosis of non-ischaemic stenosis (FFR > 0.75) is excellent and not decreased by stenting
FFR for proximal LAD lesions 852 patients with isolated proximal LAD stenosis 730 patients eligible for the study 546 patients with an FFR 0.80, treated medically 166 patients with an FFR<0.80 treated by revascularization Muller et al, JACC Interv 2011
% survival 5 year Survival 100 80 60 P = 0.0392 40 20 Medical group Revascularization group 0 0 12 24 36 48 60 Months No at risk Medical group 564 503 423 332 220 140 Revasc. group 166 150 118 88 66 44 Muller et al, JACC Interv 2011
% survival Survival in Medical & Control Group 100 80 60 P = 0.7384 40 20 Medical group Controls 0 0 12 24 36 48 60 Months No at risk Medical group 466 410 341 262 173 109 Controls 1868 1839 1803 1772 1725 1675 Muller et al, JACC Interv 2011
FFR for Multivessel Disease Common finding in angiography Treatment decision is not easy in most of the cases PCI vs medical therapy? (COURAGE) PCI vs CABG? (SYNTAX, BEST)
Inaccuracy of Perfusion SPECT imaging in MVD 143 severe 3-vessel disease patients and Tc-SPECT 3 Vessel Pattern 10% 18% No Defect 1 Vessel Pattern 36% 36% 2 Vessel Pattern Lima RS et al, JACC 2003
Patient with stenoses 50% in at least 2 of the 3 major epicardial vessels Indicate all stenoses 50% considered for stenting Randomization Angiography-guided PCI N=496 FFR-guided PCI N=509 Measure FFR in all indicated stenoses Stent all indicated stenoses Stent only those stenoses with FFR 0.80 1-year follow-up
1 Year Results from FAME 1. Improved outcomes 2. Decreased cost Absolute Difference in MACE-Free Survival 3. Less contrast use 4. Similar procedure time FFR-guided PCI Angio FFR Angio-guided PCI 5.3% 360 days p=0.02 $6,007 vs $5,332, p<0.001 302 ml vs 272 ml, p<0.001 70 min vs 71 min, p=0.51 Tonino et al, NEJM 2009
FAME: 2 years FU Fearon et al, TCT 2009
FFR for Left Main Coronary Artery Significant Left Main Coronary Artery (LMCA) stenosis is an absolute indication for surgical revascularization Incidental LMCA stenosis is a relatively common finding during routine coronary angiography In most of the cases, therapeutic decision for its treatment is based on the angiographic appearance of the lesion
FFR for LMCA estimation Total number of patients = 591 Publication Journal Pts Defer Surg FU EFS EFS Surviv Surviv (Def) (Surg) (Def) (Surg) Bech et al Heart 2001 54 24 30 29 76 83 100 97 Jasti et al Circulation 2004 51 37 14 25 90 100 100 100 Jiminez et al J Invas Card 2004 27 20 7 26 90 86 100 86 Legutko et al Kardiol Pol 2005 38 20 18 24 90 89 100 89 Suemaru et al Heart Vessels 2005 15 8 7 33 100 71 100 100 Linsdtaedt et al Am Heart J 2006 51 24 27 29 69 66 100 81 Courtis et al Am J Cardiol 2009 142 82 60 14 87 93 96 95 Hamilos et al Circulation 2009 213 138 75 36 74 83 90 85
274 patients with LMCA 26 patients with protected LMCA 10 patients with valvular disease 213 patients enrolled 4 patients requiring surgery but treated medically 21 patients requiring surgery for other vessel disease 138 Nonsurgical group 75 Surgical group 2 patients lost in FU 2 patients lost in FU 136 patients included in the analysis 73 patients included in the analysis Hamilos et al, Circulation 2009
% Survival 5-year Survival 100 80 60 40 p=0.48 FFR 0.80 FFR<0.80 20 0 0 12 24 36 48 60 No at risk Months FFR 0.80 136 103 72 52 38 26 FFR<0.80 73 56 41 30 14 10 Hamilos et al, Circulation 2009
% MACE free 5-year MACE 100 80 60 40 20 p=0.5 FFR 0.80 FFR<0.80 0 0 12 24 36 48 60 No at risk Months FFR 0.80 136 106 77 57 42 30 FFR<0.80 73 56 40 29 15 10 Hamilos et al, Circulation 2009
FFR in ACS FFR in Acute STEMI / NSTEMI FFR in Chronic MI FFR in the non culprit during STEMI / NSTEMI
FFR after myocardial infarction: Acute phase FFR=0.50 DS=75% Normal Myocardium significant Myocardial Infarction Non significant FFR=0.84 DS=75% Non-viable Stunning Normal Myocardium Microvascular Dysfunction, Thrombi
FFR after myocardial infarction: Chronic phase DS=75% FFR=0.50 Normal Myocardium significant Myocardial Infarction Non significant FFR=0.84 DS=75% Scar Normal Myocardium Capillary density Microvascular Dysfunction FFR can be used as in normal myocardium Cut-off values for FFR are the same
FFR in non-culprit lesions 101 pts, 75 STEMI, 36 NSTEMI, FFR in 112 lesions at time of PCI and 35 days later 1.00 0.95 0.90 0.85 0.80 0.75 0.70 0.65 0.60 FFR=0.77±13 0.55 0.50 0.45 0.40 0.35 FFR=0.77±13 0.30 0.25 0.20 ACUTE FOLLOW-UP p=ns Ntalianis et al. JACC Cardiovasc Intervent 2010
FFR in diffuse coronary artery disease Atherosclerosis is diffuse in nature This diffuse disease is often reponsible for a marked pressure gradient In 8% of arteries without any focal stenosis, FFR<0.75 FFR of all stenoses together can be calculated from the ratio Pd / Pa during maximal hyperemia The severity of one stenosis can be unmasked by PCI of a second stenosis
FFR post-stenting Multicenter FFR post-stent Registry / 750 patients 40% 30% 20% %MACE at 6 month follow-up 37% 28% 19% 10% 7% 4% 0% 0.75 0.80 0.85 0.90 0.95 1.00 FFR post stenting Piljs et al, Circulation 2002
FFR in Bifurcation and Coronary Artery Bypass Graft Lesions FFR can guide bifurcation PCI (Koo et al, JACC 2007, EHJ 2008) FFR for vein grafts and mammary artery has not been extensively studied. Only 1 small study exists (Aqel et al CCI 2008) It is reasonable to use FFR for grafts as in native lesions This should be done with caution until more data are available, since SVG lesions may have a different natural history
FAME II study 1832 patients With Stable CAD At least 1 stenosis 50% Measure FFR in all indicated stenoses Randomization Stenting + OMT OMT alone 2-year follow-up
Σπκπεξάζκαηα Τν FFR είλαη έλα θαιά κειεηεκέλν, απιό θαη αμηόπηζην κέζν γηα ηελ εθηίκεζε ηεο ζνβαξόηεηαο ηωλ ζηελώζεωλ ζην αηκνδπλακηθό εξγαζηήξην Τν FFR καδί κε ηηο αλαηνκηθέο πιεξνθνξίεο πνπ πξνθύπηνπλ από ηελ αγγεηνγξαθία επηηξέπνπλ ηελ πιήξε εθηίκεζε ηωλ ζηελώζεωλ κέζα ζην εξγαζηήξην Όια ηα παξαπάλω θάλνπλ ην FFR έλα αλαληηθαηάζηαην θιηληθό εξγαιείν γηα ηνλ επεκβαηηθό θαξδηνιόγν
BACK UP SLIDES
FFR 1.0 0.9 FFR and Angiography Appropriate decision Based on angiography = 65 % 0.8 0.75 0.7 Inappropriate decision Based on angiography = 35% 0.6 0.5 0.4 0.3 0.2 r=-0.53, p<0.001 0 10 20 30 40 50 60 70 80 90 100 STENOSIS% Hamilos et al ESC 2008
FFR vs Myocardial Perfusion Imaging Agreement of the 2 methods is only 42% Melikian et al, JACC Interv 2010
Adverse Events at 2 Years Angio- Guided n = 496 FFR- Guided n = 509 P Value Total no. of MACE 139 105 Individual Endpoints Death 19 (3.8) 13 (2.6) 0.25 Myocardial Infarction 48 (9.7) 31 (6.1) 0.03 CABG or repeat PCI 61 (12.3) 53 (10.4) 0.35 Composite Endpoints Death or Myocardial Infarction 63 (12.7) 43 (8.4) 0.03 Death, MI, CABG, or re-pci 110 (22.2) 90 (17.7) 0.07 Fearon et al, TCT 2009
FFR and QCA Hamilos et al, submitted
5 year Survival free from MACE (Death-MI-TVR) Muller et al, JACC Interv 2011
IU FFR in non-culprit lesions Index of Microcirculatory resistance 80 n=14 70 60 50 40 30 20 10 p=ns 0 ACUTE FOLLOW UP Ntalianis et al. JACC Cardiovasc Intervent 2010
Value of MPI for LMCA stenosis detection 101 patients with angiographic left main CAD (>50%stenosis) Berman et al, J Nucl Cardiology 2007
The Reality 23.887 patients underwent elective PCI Only 44.5% underwent a stress test before! The more experienced the physician the less the stress test was used! Lin et al JAMA 2008
FFR in diffuse coronary artery disease When 2 focal stenoses: Treat the most severe stenosis or the distal stenosis Repeat hyperemic pressure pullback afterwards When diffuse disease and no focal stenosis: Place the sensor very distal Induce steady state hyperemia (adenosine iv) Pull back manually under hyperemia and under fluoro Stent when focal hyperemic ΔP>10-15 mm Hg (empiric statement)