CORONARY PRESSURE MEASURENT AND FRACTIONAL FLOW RESERVE Coronary pressure measurement and Fractional Flow Reserve in special situations. Edinburgh, october 25th, 2002 Jan Willem Bech, MD, PhD

100 Qnormal 100 Qstenosis Myocardium Aorta coronary artery Pa Pd Qnormal Max. hyperemia Normal perfusion pressure 100 Pa Pd Qstenosis U ziet hier een schema van de aorta, een normale kransslagader en het myocard. Veronderstel nu een toestand na toediening van een maximaal hyperaemische prikkel. Met andere woorden: de bloedstroom is maximaal en de weerstand derhalve minimaal en constant. De perfusiedruk over het myocard is nu 100 mm kwik. Stel nu verder dat er een stenose ontstaat met een maximale gradient van 30mm kwik. Dan resteert achter de vernauwing nog een perfusiedruk van slechts 70mm kwik. Omdat bij maximale hyperaemie de bloedstroom door het myocard recht evenredig is met de perfusiedruk in de kransslagader voorbij de vernauwing betekent dit dat de maximale bloedstroom in aanwezigheid van de vernauwing geindexeerd voor de bloedstroom zoals deze had moeten zijn gelijk is aan de stenotische perfusiedruk in dit geval 70 gedeeld door de normale perfusiedruk van 100mm kwik waardoor de FFR nog 70% is van wat deze had moeten zijn. We zeggen dan dat de FFR 0,70 0f 70% is. Deze metingen kunnen worden gedaan met dunne PTCA voerdraden waarmee de druk kan worden gemeten. Stenotic perfusion pressure Qstenosis Stenotic perfusion press. Pd FFR = = = Qnormal Normal perfusion press. Pa

Characteristics of FFR FFR is not influenced by changes in blood pressure, heart rate, or contractility FFR has a unique normal value of 1.0 in every patient and every coronary artery FFR incorporates the contribution of collateral flow to myocardial perfusion

FFR threshold for ischemia No ischemia Yes ischemia FFR 1.00 0.75 0.00 Bovendien is er een drempewaarde van 0.75 die onderscheid maakt tussen wel of geen induceerbare ischaemie. FFR < 0.75  inducible ischemia (spec. 100 % ) FFR > 0.75  no inducible ischemia (sens. 90 % ) Pijls, De Bruyne et al, NEJM 1996

Decision making based on FFR 0.75 FFR < 0.75 ischaemia inducible: revascularization is justified. FFR > 0.75 ischaemia highly unlikely: ? is it justified to DEFER revascularization, even when the lesion is angiographically serious? DEFER STUDY: 325 pat. all accepted for elective PTCA of a single lesion. Just prior to PTCA FFR was determined. Dus bij een FFR minder dan 0.75 is revascularisatie gerechtvaaardigd. Maar geldt het omgekeerde ook. Met andere waarde: is afzien van revascularistatie gerechtvaadigd als de FFR meer dan 0.75 bedraagt. Dit was de vraag in het eerste deel van mijn proefschrift die centraal stond in de DEFER studie. In deze studie bij 325 patienten die geaccepteerd waren voor PTCA werd vooraf de FFR gemeten. Bech et al, Circulation 2001

DEFER study 144 patients FFR < 0.75 => Ischaemia 325 patients 181 patients FFR > 0.75 => No ischaemia PTCA 144 patients Randomisation Bij 144 patienten van de 325 patienten was de FFR minder 0.75 hetgeen induceerbare ischaemie bewijst. Deze patienten werden uiteraard allen gedotterd. Bij 181 patienten daarentegen was de FFR meer dan 0.75 hetgeen ischaemie onwaarschijnlijk maakt en deze patienten werden gerandomiseerd naar het wel of niet uitvoeren van PTCA. Beide groepen werden 2 jaar gevolgd. Performance of PTCA 90 patients Deferral of PTCA 91 patients 2 yr follow-up 2 yr follow-up Bech et al, Circulation 2001

DEFER 2 jaar follow-up: event-free survival No PTCA Na 2 jaar was de event-free survival in de PTCA groep, deze rode lijn, 83%, maar in de groep die geen PTCA kreeg deze blauwe lijn 89%. We moeten dus concluderen dat het dotteren van een vernauwing met een FFR van meer dan 0.75 niet zinvol is en dat deze patienten het beste medicamenteus behandeld kunnen worden. PTCA Bech et al, Circulation 2001

The DEFER Study: Conclusion In patients admitted for PTCA of a single lesion, but with a FFR more than 0.75 just prior to PTCA, deferral of revascularization is at least as good as performance of an intervention. Although these patients have angiographic CAD and are at increased risk for events as compared to the general population we can conclude that performance of an intervention does not reduce this risk.

FFR to evaluate PTCA FFR after coronary intervention should preferably be higher than 0.90 POBA: Follow-up 2 years: FFR < 0.90  event rate 41 % FFR > 0.90  event rate 15 % (Bech et al, Circulation 1999)

Multicenter registry Europe-USA-Asia 750 pat. post-STENT FFR % death, infarction, or re-intervention at 6 mnths. 40% 37% After stenting: Inverse correlation between FFR and event rate. 30% 28% 19% 20% Na stenten is dit nog veel meer uitgesproken het geval. Bij een groep van 750 patienten bij wie na stent implantatie met angiografisch optimaal resultaat de FFR werd gemeten hebben bleek bij de patienten met een FFR groter dan 0.90 dat de kans op dood infacrt of reinterventie na 6 maanden ongeveer 5% was terwijl bij hen met een FFR minder dan 0.90 dit 4 maal zo hoog lag. 10% 7% 4% 0% 0.76-0.80 0.81-0.85 0.86-0.90 0.91-0.95 0.96-1.00 Post-STENT FFR

CORONARY PRESSURE MEASUREMENT How does FFR works in complex coronary disease? difficult anatomy, poorly visible lesions, overlap multiple stenoses within one artery diffuse disease left main disease multivessel disease

Male, 67, stable angina, positive exercise test LCX D 2 RCA LAD D 1 Laten we nu eens kijken hoe deze kennis in de praktijk kan worden toegepast bij onze voorbeelden uit het begin van mijn presentatie. Bij deze patient hebben we zowel in de LAD, de diagonalen, als in de RCA de FFR bepaalt. 2 intermediate stenoses mid RCA Complex lesion proximal LAD

LAD, hyperemia Pa Pa 100 Pd Pd FFR = 92/98 = 0.94

DIAG 2, hyperemia Pa Pa 100 Pd Pd FFR = 87/97 = 0.89

DIAG 1, hyperemia Pa Pa Pd 100 Pd FFR = 87/96 = 0.90

RCA, hyperemia Pa 100 Pd FFR = 38/92 = 0.41

Balloon 3.0 mm

Pa Pd After balloon inflation 3.0 balloon 12 atm FFR = 55/82 = 0.67 100 Pd FFR = 55/82 = 0.67

Stent 3.5 mm(mid-RCA)

Stent 3.5 mm(mid-RCA) Pa 100 Pd FFR = 76/95 = 0.80

Pressure drop Pull back pressure wire

Additional Stent 3.5 mm (prox-RCA)

Pa Pd Stent 3.5 mm(mid-RCA) + Stent 3.5 mm(prox-RCA) 100 Pd FFR = 88/94 = 0.94

Use during complex interventions Pressure Wire: Use during complex interventions In this patient with complex coronary artery disease, coronary pressure measurement: confirmed the appropriateness of stenting the RCA while avoiding a riskful intervention of the LAD or bypass surgery Selected the correct spots in the RCA where to stent evaluated the result of stenting.

CORONARY PRESSURE MEASUREMENT How does FFR works in complex coronary disease? difficult anatomy, poorly visible lesions, overlap multiple stenoses within one artery diffuse disease left main disease multi vessel disease

A B

Coronary Pressure & FFR: Pull-Back Curve Focal disease: sudden changes in pressure

Coronary Pressure & FFR: Pull-Back Curve Diffuse coronary disease: gradual increase of pressure.

FFR: The Pressure Pull-back Curve By slowly retrieving the pressure wire under fluoroscopy and sustained hyperemia the individual contribution of every segment of the coronary system to the extent of disease can be studied and such spatial information cannot be obtained by any other method

CORONARY PRESSURE MEASUREMENT How does FFR works in complex coronary disease? difficult anatomy, poorly visible lesions, overlap multiple stenoses within one artery diffuse disease long and ostial lesions left main disease multivessel disease

equivocal left main coronary artery disease by Fractional Flow Reserve Decision making in equivocal left main coronary artery disease by Fractional Flow Reserve Bech et al, Heart 2001

Background The presence of angiographic clearly significant LMCA stenosis is often decisive in the choice for surgical treatment. However, often patients are encountered with angiographically an intermediate LMCA stenosis of unclear physiological significance. It is unclear whether bypass surgery should be performed.

Aim of the study To investigate the usefulness of pressure derived FFR to decide between medical versus surgical therapy in patients with equivocal LMCA disease.

Events during follow-up 54 patients FFR > 0.75 N=24 Medical Group FFR < 0.75 N=30 Surgical Group Mean follow-up (mths) 28 15 2914 Death 0 1 MI 0 1 Early re-operation -- 3 CABG 3 0 PTCA 2 0 Total 5 (21%) 5 (17%)

Conclusion FFR is useful in equivocal left main coronary artery disease. If LM FFR  0.75, a conservative medical of the LM lesion approach seems to be safe. If LM FFR < 0.75, the stenosis bears physiologic significance which justifies bypass surgery of the LM lesion.

CORONARY PRESSURE MEASUREMENT How does FFR works in complex coronary disease? difficult anatomy, poorly visible lesions, overlap multiple stenoses within one artery diffuse disease long and ostial lesions left main disease multivessel disease (submitted for publication)

Background 1 In multi-vessel disease, The most important prognostic index to predict outcome is the extent and severity of inducible ischemia. It has been demonstrated that from a symptomatic and prognostic point of view revascularization is indicated only for functionally significant (culprit) stenoses. In order to choose the optimum treatment, it is of paramount importance to know which of the angiographic stenoses are culprit and which are not.

Background 2 In multi-vessel disease, non-invasive testing can often not indicate which lesions are culprit. Fractional Flow Reserve can assess if a specific stenosis or segment is culprit or not by the ischemic threshold value of 0.75.

Aim Not to answer the question whether CABG or PCI is a better treatment in all patients with multivessel disease But to investigate which is the optimum treatment in an individual patient with multivessel disease. CABG for a patient with a large area at risk versus PCI for a patient with a limited area at risk.

Inclusion Patients with angiographically MVD Technically suitable for CABG or PCI

Procedure Multivessel coronary pressure measurement by the so called “pull-back procedure” was performed. A coronary artery was defined as culprit when FFR < 0.75. If 3 or 2 (including LAD) culprit arteries CABG was performed. If 1 or 2 (excluding LAD) culprit arteries PCI was performed.

Conclusion In multi-vessel disease, coronary pressure measurement is an excellent tool to identify the culprit lesion(s) by FFR < 0.75 and facilitates the choice for the optimum treatment modality (CABG or PCI)