SHA24/032002

FRACTIONAL FLOW RESERVE: THE PRESENT AND THE FUTURE Saudi Heart Association Rhyadh, February 14th, 2013

Nico H.J.Pijls, MD, PhD Catharina Hospital, Eindhoven The Netherlands,

EVIDENCE-BASED TREATMENT OF CORONARY ARTERY DISEASE: knowledge if and which lesion(s) are responsible for inducible ischemia, is paramount for adequate treatment in the cath.lab

EVIDENCE-BASED MEDICINE: Ischemia No ischemia

angina & worse outcome PCI or CABG indicated no angina, favourable outcome with medical treatment

(DEFER, FAME, FAME-2, COURAGE, SYNTAX,Many Nuclear Studies)

Non-invasive testing is often unreliable, Especially in multivessel disease The angiogram (and IVUS!) have fundamental shortcomings to indicate ischemia correctly Rationale of Fractional Flow Reserve

FRACTIONAL FLOW RESERVE: The index FFR (Fractional Flow Reserve) is based upon the two following principles: • It is not resting flow, but maximum achievable flow which determines the functional capacity (exercise tolerance) of a patient • At maximum vasodilation (corresponding with maximum hyperemia or with maximum exercise), blood flow to the myocardium is proportional to myocardial perfusion pressure (~hyperemic distal coronary pressure)

During Maximal Vasodilatation Pa

Pv

100

0

Pd

Pv

100 70

0

Pa

Q

P

Pd FFRmyo = Pa = 0.70

Whatever the stenosis might look like..., whatever the pressure/flow relations across the stenosis might be...., To understand the meaning of the stenosis for the patient, the MOST important number to know is the resulting distal perfusion pressure at hyperemia, as a fraction of normal perfusion pressure ( = aortic pressure) This ratio determines completely the physiologic significance of the stenosis and its consequences for the patient !!

It is called FFR

FFR myo =

Pd Pa

Pa = mean aortic pressure at maximum hyperemia Pd = mean distal coronary pressure at maximum hyperemia

Mr van Z. 77 years, stable ang 2-3 posit ET

Fractional Flow Reserve in Clinical Practice REST

HYPEREMIA

150

112

100

58

50

0

Crossing the lesion

Distal to the lesion

FFR=58/112=0.52

Application in catherization laboratory

+ pressure wire

= FFRmyo

papav./ adenosine hyperemic stimulus

0.014 sensor-tipped PTCA guidewire (St Jude Medical; Volcano)

MAXIMUM VASODILATORY STIMULI !! Maximum hyperemia is paramount !!

• PAPAVERINE i.c.

• ADENOSINE i.c.

• ADENOSINE i.v.

• ATP i.c • ATP i.v.

• regadenoson ?(!) (key papers: De Bruyne, Circulation 2003;107:1877-1883 McGeoch, CCI 2008;71:198-204

Venous sheath into femoral vein

Adenosine for i.v. infusion (standard bag 200 mg = 100 ml) Price: < 1 Euro per patient

Infusion pump for adenosine (140 Âľg/kg/min)

Infusion rate simply adjusted according to body weight ( ….kg ……ml/min)

adenosine

• no preparation in the lab • no difficult calculations • no risk of dosage error • no loss of time

infusion pump

Analyzer Some notes on your sheaths

PRACTICAL PERFORMANCE OF FFR - MEASUREMENT

Unpacking of the Pressure Wire

Flushing the Pressure Wire

Connecting the Pressure Wire to Analyzer

Calibrating Pressure Wire

Pressure Wire Calibrated: Ok

Pressure Wire introduced into Y-connector

Shaping of the tip of the PW

Introducing the PW into the Guiding Catheter

start with verification of equal signals when sensor is located at tip of the guiding catheter and equalize

pressure wire

advance pressure wire through stenosis and induce hyperemia FFR

resting

hyperemia

FFR LAD (i.v. adenosine) = 0.66

need for stent

Make pullback recording for optimal information

Because sensor is 3 cm from tip, easily pull-back and push-up for exact spatial information.

If desirable, perform pull-back recording for exact location of pressure drop / stent deposition

Pull-back & Advance Pull-back recording for detailed spatial information about distribution of lesions along the complete artery

to assess collateral flow: measurement of coronary wedge pressure during balloon inflation can be done

coronary wedge pressure

balloon inflation

balloon deflation Fractional collateral flow = (Pd-Pw) / (Pa-Pw)

Stent has been placed: LAD after stenting

resting

hyperemia

measurement of FFR after stenting to assess result FFR = 0.94

no drift has occurred

At the end, when sensor is back at tip of guiding catheter, verify absence of drift

FEATURES OF FFR • Normal value = 1.0 for every patient and every artery • FFR is not influenced by changing hemodynamic conditions (heart rate, blood pressure, contractility) • FFR specifically relates the influence of the epicardial stenosis to myocardial perfusion area and blood flow • FFR accounts for collaterals • FFR has a circumscript threshold value (~ 0.75 – 0.80 ) to indicate ischemia • FFR is easy to measure (success rate 99 %) and extremely reproducible • Pressure measurement has un unequaled spatial resolution

AORTA 100 mmHg

pressure (Pd) (mm Hg)

Normal FFR = 1.0 irrespective Where it is measured

200

100

IVUS-CSA flow (Q) (ml/min)

9 mm2

100

150

100

100

7 mm2

100

75

5 mm2

100

50

100

APEX

25

3 mm2

Fractional Flow Reserve in Normal Coronary Arteries 33 truely normal coronary arteries in patients\ without coronary artery disease:

FFR = 0.98 +/- 0.02 (range 0.93 â&#x20AC;&#x201C; 1.00 ) Pijls, Circulation 1995;92: 183-193

86 apparently normal contralateral arteries In patients with coronary disease:

FFR = 0.87 +/- 0.09 ( range 0.64 â&#x20AC;&#x201C; 0.97) De Bruyne, Circulation 2001; 104:2401-2406

Reproducibility of FFR

N=200

VERIFY study, Berry et al, JACC 2013 ( published februari 2013)

There is not any other index in physiology so reproducible as FFR

Threshold value of FFR to detect significant stenosis

FFR

non-signif.

1.0

0.80

stenosis significant 0.75

0

FFR is the only functional index which has ever been validated versus a true gold standard.

(Prospective multi-testing Bayesian methodology) ALL studies ever performed in a wide variety of clinical & angiographic conditions, found threshold between 0.75 and 0.80

Sensitivity : 90% Specificity : 100%

N Engl J Med 1996; 334:1703-1708; 28 other prospective studies

FFR has important prognostic implications: (DEFER, FAME, FAME-2 and many other studies): • FFR guided PCI decreases mortality & AMI rate after 1 and 2 years by 30% • decreases rate of repeat revascularization by 25% • does hardly prolong the PCI procedure • is cost-saving • and improves functional class up to 5 years after PCI

Is hyperemia truly mandatory?

Hyperemic indices: • FFR ( Pijls, De Bruyne 1992 ) • iHDPVr ( Di mario, Serruys 1994 ) • hSRv ( Piek, Spaan, Siebes 1997)

Resting indices: • resting transtenotic gradient (Gruentzig, 1977) • Pd/Pa at rest (Gould,Meier, 1981) • iFR (Sen, Davies 2011) • bSRv (Verhoef, Siebes 2012)

Virtual Hyperemic Index • FFR by CT ( Min, Taylor, Koo, 2009)

Î&#x201D;P = f.Q + s.Q2 f = friction coefficient

s = separation coefficient

Moderate gradient at rest

Small gradient at rest

Moderate increment at hyperemia

Large gradient at hyperemia

70% long prox LAD stenosis

iFR = 0.89 FFR = 0.85

50% short ostial left main stenosis

iFR = 0.94 FFR = 0.57

(N=1539)

Jeremias et al, TCT 2012

VERIFY study, Berry et al, JACC 2013 ( published early 2013) N= 700

• In those 25-30% of patients with resting Pd/Pa or iFR < 0.80 as a matter of fact FFR will be < 0.80 anyway and if you just like to figure out if there is inducible ischemia, no additional hyperemia is necessary and stenting is indicated anyway • …..but even then you cannot tell then how much your patient improves by stenting !! (“did your FFR increase from ,for example, 0.58 to 0.94 or from 0.76 to 0.94”) • …and without hyperemia, it is fundamentally impossible to make a pressure pullback recording. So even in those 25-30 % of the cases, you are loosing your spatial information completely!

Without hyperemic pullback recording, a lot of information is lost

Male, 69-year-old Angina class 3 Positive Mibi-Spect inferior wall

LCX, hyperemia , pull back recording

proximal CX

Pull-back recording LAD

distal

proximal

Without hyperemic pullback recording, a lot of information is lost

Male, 69-year-old Angina class 3 Positive Mibi-Spect inferior wall

Is hyperemia truly mandatory?

YES, it is !!

Do not accept inferior standards!

Patients are too precious for that!

Berry C, Oldroyd K, et al: VERIFY study, JACC 2013 (febr, on-line) Johnson N, Gould KL, et al: JACC 2013 (febr, on-line) Jeremias A, Stone G, et al: RESOLVE trial (TCT 2012)

FRACTIONAL FLOW RESERVE 1996-2012: • from intermediate stenosis  complex disease • from simple diagnostic tool  improved outcome • from adjunctive therapy  booster of PCI

THE FUTURE: • further expansion of use of FFR

• wireless system  accomplished yet (Aeris) • zeroing and calibration within a second (Aeris System, SJM) • Integration of FFR in regular cathlab equipment (General Electric & SJM) • remote control sensor • new hyperemic stimuli (regadenoson) • non-invasive FFR

True FFR Integration (St Jude Medical ) • • • • •

Receiver connects directly to any hemodynamic recording system.

Used directly in the cathlab with no additional instrumentation.

Utilizes the standard blood pressure transducer ports without any extra cabling.

Requires FFR software upgrade from cathlab manufacturers General Electric, Philips, etc No calibration, ready in 1 second PressureWire® Receiver

PressureWire® Aeris

P2 P1 AO-transducer

Hemodynamic recording system

Identical display on Analyzer or Quantien and GE cathlab recording system

IMPACT OF FAME-studies ON USE OF PRESSURE WIRE

• worldwide sales from 90.000 end of 2008 to 300.000 in 2012 (= 12% of all PCI) • integration of FFR with regular cathlab equipment and wireless sensors will have further positive impact (General Electric & SJM) • common educational efforts of SJM and Volcano will be important; commercially-driven confounders (like iFR) should be avoided

THE FUTURE: • further expansion of use of FFR

• wireless system  accomplished yet (Aeris) • zeroing and calibration within a second (Aeris System, SJM) • Integration of FFR in regular cathlab equipment (General Electric & SJM) • remote control sensor • new hyperemic stimuli (regadenoson) • non-invasive FFR

REGADENOSON (RAPISCAN R) • new hyperemic stimulus, to be admistered as single bolus of 5cc (400 ug) in either central or peripheral vein • maximum hyperemia, identical to central venous adenosine, within 1 minute and lasting for 1-7 minutes (variable) • sufficiently long hyperemia for pressure pullback recording • we use it in our lab for simple procedures and in radial access. In complex cases, we do femoral approach with central intravenous adenosine

Nair et al, JACC Interv 2011; 4:1085-1092

THE FUTURE: • further expansion of use of FFR

• wireless system  accomplished yet (Aeris) • zeroing and calibration within a second (Aeris System, SJM) • Integration of FFR in regular cathlab equipment (General Electric & SJM) • remote control sensor • new hyperemic stimuli (regadenoson) • non-invasive FFR

FFR CT : Complementary or Substitution?

Case Examples: Obstructive CAD B

A

CT stenosis of the proximal LAD

D

CT stenosis of the mid RCA

C

FFRCT 0.62 = Vessel ischemia

ICA stenosis of LAD; FFR 0.65 = Vessel ischemia

E

ICA stenosis of RCA; FFR 0.86 = No vessel ischemia

F

FFRCT 0.87 = No vessel ischemia

FFR CT : Complementary or Substitution?

Discover-Flow study: false-positive rate of CT-angio decreased from 38 %  11 % by using FFR CT De Facto study: diagnostic accuracy of CT-angio increased from 57%  73 % by using FFR CT

FFR CT : Complementary or Substitution?

• FFR CT is not good enough to replace invasive FFR….

• …….But by using it, screening of larger populations

by CCTA might become attractive because the high number of false positive CT angio’s might be decreased.

FFRCT might expand the interest in coronary physiology outside the cath lab, to the world of non-invasive cardiologists and radiologists …and thereby boost the use of invasive FFR !!!

Large prospective study mandatory to support this standpoint

FFR: the present and the future

CONCLUSIONS

. FFR is the gold standard for decision making in the cath lab with respect to revascularisation and has important prognostic implications.

Its use increased from 5 % of all PCI in 2008 to 12 % in 2012 and is anticipated to be 25-30 % in 2016

. Hyperemia remains paramount.

Just relying upon resting indexes is like testing in a windtunnel without wind! It is a step back in time and making a guess instead of getting certainty.

FFR: the present and the future

CONCLUSIONS (continued) 3. FFRCT might improve the specificity of CT-angio and

therefore extend the use of CCTA to screening of larger populations.

Further prospective studies are mandatory

4. Regadenoson might be a good alternative for i.v adenosine, especially in simple cases and radial procedures.

Generally it allows pressure pullback recordings but disadvantage is variable lenght of max hyperemia.

Large studies are underway (expected august 2013)

Arthur Schopenhauer 1788â&#x20AC;&#x201C;1860

Foto (WinklerPrins)

THE END