Fractional Flow ReserveFractional Flow Reserve

Dr. Surinder Singh HansraNanavati Hospital

Mumbai

Normal Coronary PhysiologyNormal Coronary Physiology In normal hearts, the flow of blood to the myocardium is controlled In normal hearts, the flow of blood to the myocardium is controlled

mainly by constriction and dilatation of the microcirculation (vessels mainly by constriction and dilatation of the microcirculation (vessels <400µm in diameter). <400µm in diameter).

As a stenosis develops, a drop in blood pressure occurs across the As a stenosis develops, a drop in blood pressure occurs across the stenotic lesion and the microvessels dilate to compensate for the stenotic lesion and the microvessels dilate to compensate for the reduced distal arterial perfusion pressure, maintaining normal resting reduced distal arterial perfusion pressure, maintaining normal resting blood flow.blood flow.

Coronary blood flow can increase to 3.5 to 8 times the resting flowCoronary blood flow can increase to 3.5 to 8 times the resting flow

Resting blood flow does not decrease until more than 85-90% of the Resting blood flow does not decrease until more than 85-90% of the arterial lumen is occluded. arterial lumen is occluded.

Hyperemic blood flow begins to fall when about 45-60% of the cross-Hyperemic blood flow begins to fall when about 45-60% of the cross-sectional area of an artery is stenosed and is abolished above 90%.sectional area of an artery is stenosed and is abolished above 90%.

Our Preoccupation With AngiographyOur Preoccupation With Angiography Angiography depicts coronary anatomy from a planar 2D silhouette of the lumen. Angiography depicts coronary anatomy from a planar 2D silhouette of the lumen.

Confounding factors like vessel tortuosity, overlap of structures, and the effects of Confounding factors like vessel tortuosity, overlap of structures, and the effects of lumen shape lumen shape

Clinically significant intraobserver and interobserver variability, with differences in Clinically significant intraobserver and interobserver variability, with differences in the estimation of stenosis severity approaching 50% the estimation of stenosis severity approaching 50%

Major discrepancies between the apparent angiographic severity of lesions and Major discrepancies between the apparent angiographic severity of lesions and postmortem histologypostmortem histology

Necropsy and IVU studies demonstrate that mechanical interventions exaggerate the Necropsy and IVU studies demonstrate that mechanical interventions exaggerate the extent of luminal eccentricity by fracturing or dissecting the atheromaextent of luminal eccentricity by fracturing or dissecting the atheroma

Limited value in evaluating the functional significance of intermediate coronary Limited value in evaluating the functional significance of intermediate coronary lesionslesions

Physiological assessment of stenosisPhysiological assessment of stenosis Early investigators tried to measure absolute flow, which however, varies widely between Early investigators tried to measure absolute flow, which however, varies widely between

different persons and between different coronary arteries. different persons and between different coronary arteries.

CFR by Gould et al in 1974, defined as the ratio of hyperemic to resting flow in a coronary CFR by Gould et al in 1974, defined as the ratio of hyperemic to resting flow in a coronary artery. Hhowever, the dependency of absolute CFR on hemodynamic loading conditions, artery. Hhowever, the dependency of absolute CFR on hemodynamic loading conditions, heart rate, and some other confounding factors has hampered its use, and normal values show heart rate, and some other confounding factors has hampered its use, and normal values show a considerable interstudy variability. a considerable interstudy variability.

Relative CFR, defined as hyperemic flow in the stenotic artery divided by hyperemic flow in Relative CFR, defined as hyperemic flow in the stenotic artery divided by hyperemic flow in a normal reference artery, is independent of pressure changes but is applicable only if a a normal reference artery, is independent of pressure changes but is applicable only if a normal reference artery is available. normal reference artery is available.

Both absolute and relative CFRs do not take into account collateral blood flow, which may Both absolute and relative CFRs do not take into account collateral blood flow, which may contribute considerably to myocardial perfusion and modify the functional significance of the contribute considerably to myocardial perfusion and modify the functional significance of the coronary stenosis.coronary stenosis.

Therefore, concept of FFR (Pijls et al 1993) as the maximum achievable blood flow in the Therefore, concept of FFR (Pijls et al 1993) as the maximum achievable blood flow in the presence of a stenosis divided by maximum flow in that same distribution as it would be if presence of a stenosis divided by maximum flow in that same distribution as it would be if the supplying artery were normal.the supplying artery were normal.

Does a coronary lesion confer additional risk because it has become flow-limiting? There is Does a coronary lesion confer additional risk because it has become flow-limiting? There is ample inferential evidence that patients with physiologically important stenoses are at ample inferential evidence that patients with physiologically important stenoses are at increased risk for myocardial infarction and death increased risk for myocardial infarction and death

Features of FFRFeatures of FFR FFR has several advantages FFR has several advantages

FFR is completely independent of changes in heart rate, blood FFR is completely independent of changes in heart rate, blood pressure, and contractilitypressure, and contractility

FFR has a unique and unequivocal normal value of 1.0 in every FFR has a unique and unequivocal normal value of 1.0 in every patient patient

It takes into account the contribution of the collateral flow and, It takes into account the contribution of the collateral flow and, because there is no need for a normal reference artery, it can be because there is no need for a normal reference artery, it can be applied in multivessel disease and for serial lesions within one vesselapplied in multivessel disease and for serial lesions within one vessel

Calculation of FFR by pressure measurements has a sound scientific Calculation of FFR by pressure measurements has a sound scientific basis and has been validated in animals and humans basis and has been validated in animals and humans

Specificity and sensitivity of 100% and 88%, respectivelySpecificity and sensitivity of 100% and 88%, respectively

Rationale of FFRRationale of FFR The functional state of a patient with a coronary artery stenosis is determined by the The functional state of a patient with a coronary artery stenosis is determined by the

maximum blood flow that can reach the dependent myocardium. As soon as maximum blood flow that can reach the dependent myocardium. As soon as maximum achievable blood flow, at a given level of exercise, is no longer sufficient maximum achievable blood flow, at a given level of exercise, is no longer sufficient to match oxygen demand, myocardial ischaemia occurs. Therefore, fundamentally, to match oxygen demand, myocardial ischaemia occurs. Therefore, fundamentally, it is maximum blood flow that should be studied to establish the physiological it is maximum blood flow that should be studied to establish the physiological significance of a coronary stenosis. significance of a coronary stenosis.

FFR represents that fraction of normal maximum flow that is still achievable despite FFR represents that fraction of normal maximum flow that is still achievable despite the presence of the epicardial coronary stenosis. the presence of the epicardial coronary stenosis.

During maximal vasodilatation, the peripheral resistances are minimal and flow is During maximal vasodilatation, the peripheral resistances are minimal and flow is determined mainly by the severity of the narrowing. Accordingly, measurements determined mainly by the severity of the narrowing. Accordingly, measurements performed under conditions of are more sensitive measures of stenosis severity.performed under conditions of are more sensitive measures of stenosis severity.

In addition, from a clinical point of view, the functional capacity and the complaints In addition, from a clinical point of view, the functional capacity and the complaints of patients with ischemic heart disease are determined mainly by the maximal of patients with ischemic heart disease are determined mainly by the maximal achievable myocardial blood flow rather than by the resting flow.achievable myocardial blood flow rather than by the resting flow.

As distal pressure is also affected by the extent of the collateral circulation, FFR As distal pressure is also affected by the extent of the collateral circulation, FFR also incorporates the effects of collaterals on myocardial perfusion.also incorporates the effects of collaterals on myocardial perfusion.

Schematic illustration of the coronary artery and its dependent myocardial vascular bed

Concept of FFRConcept of FFR FFRFFRmyomyo is defined as maximum myocardial blood flow distal to an epicardial stenosis divided is defined as maximum myocardial blood flow distal to an epicardial stenosis divided

by its value if no epicardial stenosis were present by its value if no epicardial stenosis were present

FFRmyo = (Pd-Pv) / (Pa-Pv)FFRmyo = (Pd-Pv) / (Pa-Pv)

FFRFFRcorcor is defined as the maximum coronary flow in the presence of a stenosis divided by the is defined as the maximum coronary flow in the presence of a stenosis divided by the normal maximum flow of the artery (ie, the maximum flow in that artery if no stenosis were normal maximum flow of the artery (ie, the maximum flow in that artery if no stenosis were present).present).

FFRcor = (Pd-Pw) / (Pa-Pw)FFRcor = (Pd-Pw) / (Pa-Pw)

Pa, Pd, and Pv are taken at maximum vasodilation and Pw is taken at coronary occlusion. Pa, Pd, and Pv are taken at maximum vasodilation and Pw is taken at coronary occlusion.

Because of the necessity to know Pw, FFRcor can be calculated only during PTCA. FFRmyo, Because of the necessity to know Pw, FFRcor can be calculated only during PTCA. FFRmyo, however, can also be calculated during diagnostic procedures. however, can also be calculated during diagnostic procedures.

The difference between FFRmyo and FFRcor represents the contribution of collateral flow to The difference between FFRmyo and FFRcor represents the contribution of collateral flow to total myocardial perfusion and is called fractional collateral flow (FFRtotal myocardial perfusion and is called fractional collateral flow (FFR collcoll))

Because FFRmyo reflects both antegrade and collateral contribution to maximum myocardial Because FFRmyo reflects both antegrade and collateral contribution to maximum myocardial perfusion, it is the most important flow index from a clinical point of view. It describes to perfusion, it is the most important flow index from a clinical point of view. It describes to what extent maximum myocardial perfusion is affected by the epicardial coronary stenosis, what extent maximum myocardial perfusion is affected by the epicardial coronary stenosis,

The Cut-Off Value and its CorrelationThe Cut-Off Value and its Correlation It has been convincingly demonstrated that an FFR value < 0.75 discriminates functionally It has been convincingly demonstrated that an FFR value < 0.75 discriminates functionally

significant lesions.significant lesions.

A FFR of less than 0.75 is has been found to correlate well with the presence of ischaemia as A FFR of less than 0.75 is has been found to correlate well with the presence of ischaemia as measured by noninvasive testing modalities such as perfusion scintigraphy, stress measured by noninvasive testing modalities such as perfusion scintigraphy, stress echocardiography, and bicycle exercise testing.echocardiography, and bicycle exercise testing.

FFR correlates more closely to relative flow reserve derived from PET than angiographic FFR correlates more closely to relative flow reserve derived from PET than angiographic parameters parameters

FFR has a significant relationship with scintigraphic evidence of myocardial ischemia and FFR has a significant relationship with scintigraphic evidence of myocardial ischemia and can be regarded as a of its presence or absence in patients in actual clinical settings. can be regarded as a of its presence or absence in patients in actual clinical settings.

In a recent study, FFR more or less than 0.75 was compared directly to an ischaemic gold In a recent study, FFR more or less than 0.75 was compared directly to an ischaemic gold standard of all presently used non-invasive tests. Its diagnostic accuracy to predict inducible standard of all presently used non-invasive tests. Its diagnostic accuracy to predict inducible ischaemia correctly was approximately 95%, and exceeded the diagnostic accuracy of ischaemia correctly was approximately 95%, and exceeded the diagnostic accuracy of thallium exercise testing and DSE when performed as single tests.thallium exercise testing and DSE when performed as single tests.

Pijls et al showed that a cutoff value of 0.75 reliably detects ischaemia-producing lesions for Pijls et al showed that a cutoff value of 0.75 reliably detects ischaemia-producing lesions for patients with moderate coronary stenosis and chest pain of uncertain origin, with a sensitivity patients with moderate coronary stenosis and chest pain of uncertain origin, with a sensitivity of 88%, specificity of 100%, and diagnostic accuracy of 93%. of 88%, specificity of 100%, and diagnostic accuracy of 93%.

InstrumentationInstrumentation The use of an infusion catheter is not recommended for coronary pressure The use of an infusion catheter is not recommended for coronary pressure

measurement, as unpredictable and significant overestimation of the pressure measurement, as unpredictable and significant overestimation of the pressure gradient may occur, resulting in underestimated FFR readings.gradient may occur, resulting in underestimated FFR readings.

At present, two FDA-approved pressure wire systems are available: Pressure At present, two FDA-approved pressure wire systems are available: Pressure Analyser (RADI Medical Systems, Sweden) and WaveMap (Volcano Therapeutics Analyser (RADI Medical Systems, Sweden) and WaveMap (Volcano Therapeutics Inc., USA). These systems both use .014- in. wire with a pressure sensor located 3 Inc., USA). These systems both use .014- in. wire with a pressure sensor located 3 cm proximal to the wire tip, which can be used as a primary angioplasty guidewire.cm proximal to the wire tip, which can be used as a primary angioplasty guidewire.

Even though 6F or 7F guiding catheters are recommended for FFR measurement, a Even though 6F or 7F guiding catheters are recommended for FFR measurement, a recent study has demonstrated that FFR measurement can also be safely performed recent study has demonstrated that FFR measurement can also be safely performed through a conventional 4F diagnostic catheter. through a conventional 4F diagnostic catheter.

Intracoronary nitroglycerin and heparin are first administered according to the Intracoronary nitroglycerin and heparin are first administered according to the standard protocol. Afterwards, the pressure-sensing guidewire is zeroed, introduced standard protocol. Afterwards, the pressure-sensing guidewire is zeroed, introduced into the guiding catheter and advanced to its tip. into the guiding catheter and advanced to its tip.

At this point, the equality of the pressures recorded from both pressure-sensing At this point, the equality of the pressures recorded from both pressure-sensing guidewire and guiding catheters is verified. guidewire and guiding catheters is verified.

The pressure-sensing guidewire is then further advanced and positioned at least 2 The pressure-sensing guidewire is then further advanced and positioned at least 2 cm beyond the stenosis. The aortic pressure and distal coronary pressure are cm beyond the stenosis. The aortic pressure and distal coronary pressure are measured continuously by the guiding catheter and pressure-sensing guidewire. measured continuously by the guiding catheter and pressure-sensing guidewire.

After the pressures stabilise, maximum coronary hyperaemia is induced by either After the pressures stabilise, maximum coronary hyperaemia is induced by either intracoronary (IC) bolus administration or through continuous intravenous (IV) intracoronary (IC) bolus administration or through continuous intravenous (IV) infusion of vasodilator agent, and FFR is then calculated.infusion of vasodilator agent, and FFR is then calculated.

Vasodilator drugsVasodilator drugs

AdenosineAdenosine

IC 20 -30µg in RCA IC 20 -30µg in RCA

30 -50µg in LCA 30 -50µg in LCA

100µg / incremental doses (poor responders)100µg / incremental doses (poor responders)

IV 140 µg/kg/min IV 140 µg/kg/min

DopamineDopamine IV 10-40 µg/kg/min IV 10-40 µg/kg/min

Papaverine IC 20mgPapaverine IC 20mg

Dipyridamole Dipyridamole

The DilemmaThe Dilemma

Is this lesion the cause of my patient's ischemia?

What is the prognostic outcome of my intervention?

Determination of the clinical significance and severity of coronary stenoses is difficult. While the angiogram remains an indispensible roadmap, it cannot identify which lesions are functionally significant, and whether treatment will relieve the patient’s symptoms.

INDICATIONSINDICATIONS

Diagnostic Diagnostic

Ambiguous ‘intermediate’lesionsAmbiguous ‘intermediate’lesions

Inconclusive or lack of noninvasive testsInconclusive or lack of noninvasive tests

TherapueticTherapuetic

on-line assessment of PTCAon-line assessment of PTCA

Clinical ApplicationsClinical ApplicationsDIAGNOSTIC ANGIOGRAPHYDIAGNOSTIC ANGIOGRAPHY The best established indication for FFR is as a diagnostic tool to determine whether The best established indication for FFR is as a diagnostic tool to determine whether

a particular coronary stenosis, found at angiography, is responsible for reversible a particular coronary stenosis, found at angiography, is responsible for reversible ischaemia (and consequently should be dilated or bypassed if medical treatment ischaemia (and consequently should be dilated or bypassed if medical treatment fails). fails).

Specific applications in this respect are the intermediate stenosis, identification of Specific applications in this respect are the intermediate stenosis, identification of the culprit lesion in case of multivessel disease, justifi-cation to perform (or avoid) the culprit lesion in case of multivessel disease, justifi-cation to perform (or avoid) angioplasty in a patient without documented evidence of ischaemia at non-invasive angioplasty in a patient without documented evidence of ischaemia at non-invasive testing, and to indicate the exact location of a lesion in case of over projection and testing, and to indicate the exact location of a lesion in case of over projection and other situations where the angiographic image is unclear. other situations where the angiographic image is unclear.

It has been shown retrospectively that it is safe to defer an intervention when FFR It has been shown retrospectively that it is safe to defer an intervention when FFR exceeds 0.75 (DEFER study) exceeds 0.75 (DEFER study)

CORONARY INTERVENTIONCORONARY INTERVENTION It has been shown that a high value of FFR after regular balloon angioplasty is It has been shown that a high value of FFR after regular balloon angioplasty is

associated with a favourable long term outcome.associated with a favourable long term outcome.

In a study, in patients with a post PTCA FFR of > 0.90, restenosis rates at 6, 12, and In a study, in patients with a post PTCA FFR of > 0.90, restenosis rates at 6, 12, and 24 months’ follow up were 11%, 12%, and 15%, respectively, compared with 29%, 24 months’ follow up were 11%, 12%, and 15%, respectively, compared with 29%, 32%, and 42% in patients with a similar angiographic result but an FFR< 0.90.32%, and 42% in patients with a similar angiographic result but an FFR< 0.90.

In patients with chest pain referred for PTCA of an intermediate stenosis, deferral of In patients with chest pain referred for PTCA of an intermediate stenosis, deferral of the intervention on the basis of an FFRmyo > or = 0.75 is safe and is associated the intervention on the basis of an FFRmyo > or = 0.75 is safe and is associated with a much lower clinical event rate (<10% in 2years) than if the procedure had with a much lower clinical event rate (<10% in 2years) than if the procedure had been performed in these patients.been performed in these patients.

In a recent study, observations were made comparing both pressure measurements In a recent study, observations were made comparing both pressure measurements and intracoronary ultrasound (ICUS) side by side to evaluate optimal stent and intracoronary ultrasound (ICUS) side by side to evaluate optimal stent deployment and an almost perfect correlation was found between optimum stent deployment and an almost perfect correlation was found between optimum stent deployment according to ICUS criteria and complete disappearance of the pressure deployment according to ICUS criteria and complete disappearance of the pressure

gradient across the stent.gradient across the stent.

FFR as a predictor of PTCA outcomeFFR as a predictor of PTCA outcome

11

32

11

35

15

42

0

5

10

15

20

25

30

35

40

45

Event rate%

6 mth 12 mth 24mth

FFR>0.9FFR<0.9

Myocardial infarction (MI)Myocardial infarction (MI) The differences between a region with and a region without prior MI are the mass of viable The differences between a region with and a region without prior MI are the mass of viable

myocardium is smaller for a similar degree of stenosis and the infarct-related resistive vessel myocardium is smaller for a similar degree of stenosis and the infarct-related resistive vessel dysfunction may blunt maximal hyperemic response.dysfunction may blunt maximal hyperemic response.

But as both the decrease of viable myocardium and impairment of coronary resistance vessels But as both the decrease of viable myocardium and impairment of coronary resistance vessels are matched in the infarcted area, and FFR is still a reliable indicator for predicting inducible are matched in the infarcted area, and FFR is still a reliable indicator for predicting inducible ischaemia, even if the angiographic image of a stenosis might be more severeischaemia, even if the angiographic image of a stenosis might be more severe

Claeys et al. provide data that FFR is minimally affected in patients with severely impaired Claeys et al. provide data that FFR is minimally affected in patients with severely impaired microvascular function and may still be applied to patients with recent MI.microvascular function and may still be applied to patients with recent MI.

De Bruyne and colleagues have demonstrated that FFR assessment criteria are also valid in De Bruyne and colleagues have demonstrated that FFR assessment criteria are also valid in detecting reversible ischaemia in patients at least 6 days after an MI with a “grey area” of detecting reversible ischaemia in patients at least 6 days after an MI with a “grey area” of FFR measurements of 0.72–0.8, with a sensitivity of 82% and specificity of 87%.FFR measurements of 0.72–0.8, with a sensitivity of 82% and specificity of 87%.

Usui et al. comparing FFR and thallium scan also showed that FFR is reliable in assessing Usui et al. comparing FFR and thallium scan also showed that FFR is reliable in assessing coronary artery stenosis in patients with previous MI, with a sensitivity of 79% and coronary artery stenosis in patients with previous MI, with a sensitivity of 79% and specificity of 79%.specificity of 79%.

FFR guidance for PCI of acute myocardial infarction is a useful, low-cost technique that FFR guidance for PCI of acute myocardial infarction is a useful, low-cost technique that results in similar clinical outcomes as primary stenting. results in similar clinical outcomes as primary stenting.

Unstable anginaUnstable angina It was believed that in UA the maximal hyperaemic flow can be lower than in patients with It was believed that in UA the maximal hyperaemic flow can be lower than in patients with

stable angina. Consequently, the 0.75 cutoff value of FFR might not be valid in these stable angina. Consequently, the 0.75 cutoff value of FFR might not be valid in these patients. A recent study by Leesar et al. of patients with UA or NSTEMI demonstrated that patients. A recent study by Leesar et al. of patients with UA or NSTEMI demonstrated that the FFR assessment criteria based on the 0.75 cutoff is also valid in this patient group and is the FFR assessment criteria based on the 0.75 cutoff is also valid in this patient group and is superior to a more conservative approach based on stress perfusion scintigraphy. superior to a more conservative approach based on stress perfusion scintigraphy.

Multivessel coronary diseaseMultivessel coronary disease Iidentifying patients with multivessel disease who might benefit from catheter-based Iidentifying patients with multivessel disease who might benefit from catheter-based

treatment instead of surgical revascularisation. treatment instead of surgical revascularisation.

If acceptable physiologic assessment criteria are met for all the lesions, catheter-based If acceptable physiologic assessment criteria are met for all the lesions, catheter-based treatment or coronary bypass surgery can be safely deferred and medical treatment, which is treatment or coronary bypass surgery can be safely deferred and medical treatment, which is safer and may eventually result in a better outcome, should be used instead. safer and may eventually result in a better outcome, should be used instead.

In multivessel coronary disease, it is important to know which particular lesion is In multivessel coronary disease, it is important to know which particular lesion is physiologically significant and responsible for reversible ischaemia. With the help of FFR physiologically significant and responsible for reversible ischaemia. With the help of FFR measurement, it is now possible to identify one or more culprit lesions in this type of patients measurement, it is now possible to identify one or more culprit lesions in this type of patients so that catheter-based treatment of culprit lesions can be performed. Chamuleau et al. showed so that catheter-based treatment of culprit lesions can be performed. Chamuleau et al. showed that FFR is more useful than single-photon emission computed tomography for clinical that FFR is more useful than single-photon emission computed tomography for clinical decision-making and risk stratification in patients with multivessel disease.decision-making and risk stratification in patients with multivessel disease.

Left main coronary artery (LMCA) diseaseLeft main coronary artery (LMCA) disease Assist decision-making in patients with intermediate LMCA disease, in order to determine Assist decision-making in patients with intermediate LMCA disease, in order to determine

whether or not CABG should be performed.whether or not CABG should be performed.

If the FFR measurement in a case of intermediate LMCA disease is greater than 0.75, CABG If the FFR measurement in a case of intermediate LMCA disease is greater than 0.75, CABG is not needed and a safer medical treatment approach can be used instead. Bech et al. is not needed and a safer medical treatment approach can be used instead. Bech et al. demonstrated that FFR is a lesion-specific index to quantify reversible ischaemia caused by demonstrated that FFR is a lesion-specific index to quantify reversible ischaemia caused by LMCA disease, and that deferral of surgical treatment is safe if the FFR value is greater than LMCA disease, and that deferral of surgical treatment is safe if the FFR value is greater than 0.75. In the 54 patients they studied followed-up was 29 months the survival rates of the 0.75. In the 54 patients they studied followed-up was 29 months the survival rates of the patients in the medical treatment and surgical groups were 100% and 97%, respectively. The patients in the medical treatment and surgical groups were 100% and 97%, respectively. The event-free survival was 76% in the medical treatment group and 83% in the surgical group. event-free survival was 76% in the medical treatment group and 83% in the surgical group. No death or acute myocardial infarction occurred in any of the deferred patients.No death or acute myocardial infarction occurred in any of the deferred patients.

Diffuse and long lesionsDiffuse and long lesions In order to quantify lesion severity in a diffusely affected coronary vessel, a pressure pull-In order to quantify lesion severity in a diffusely affected coronary vessel, a pressure pull-

back curve is needed. This can be done by withdrawing the pressure-sensing guidewire from back curve is needed. This can be done by withdrawing the pressure-sensing guidewire from a distal to a proximal position very slowly during a steady-state maximum hyperaemia.a distal to a proximal position very slowly during a steady-state maximum hyperaemia.

This curve represents the pressure gradient over the entire length of the vessel, and clearly This curve represents the pressure gradient over the entire length of the vessel, and clearly demonstrates the exact location and severity of the lesion. This so-called pull-back curve is demonstrates the exact location and severity of the lesion. This so-called pull-back curve is extremely useful in guiding spot-stenting in a vessel with long and diffuse lesions.extremely useful in guiding spot-stenting in a vessel with long and diffuse lesions.

Tandem lesionsTandem lesions In the case of tandem lesions, the haemodynamic significance of each individual lesion is influenced by In the case of tandem lesions, the haemodynamic significance of each individual lesion is influenced by

the presence of the other lesion. the presence of the other lesion.

The FFR of each individual lesion cannot be calculated by the simple classical equation as for a single The FFR of each individual lesion cannot be calculated by the simple classical equation as for a single lesion. To obtain accurate FFR measurements in arteries with tandem lesions, a more complex approach lesion. To obtain accurate FFR measurements in arteries with tandem lesions, a more complex approach must be used. De Bruyne et al have developed equations for predicting the FFR of each individual lesion must be used. De Bruyne et al have developed equations for predicting the FFR of each individual lesion separately in the case of tandem lesions, and these equations have been validated successfully in animals separately in the case of tandem lesions, and these equations have been validated successfully in animals and humans.and humans.

Transplant vasculopathyTransplant vasculopathy Cardiac allograft vasculopathy (CAV) is the major cause of mortality and morbidity after the first year of Cardiac allograft vasculopathy (CAV) is the major cause of mortality and morbidity after the first year of

heart transplantation.heart transplantation.

Of all treatment options, such as PCI, repeat cardiac transplantation, and CABG, the long-term results are Of all treatment options, such as PCI, repeat cardiac transplantation, and CABG, the long-term results are poor.poor.

Casella et al. reported a case in which FFR measurement was used to guide and monitor the results of Casella et al. reported a case in which FFR measurement was used to guide and monitor the results of

coronary balloon angioplasty on a CAV patient and the results seem very promising. In addition, a recent coronary balloon angioplasty on a CAV patient and the results seem very promising. In addition, a recent study by Fearon et al. on suggested that the use of physiologic assessment techniques is feasible for study by Fearon et al. on suggested that the use of physiologic assessment techniques is feasible for screening asymptomatic cardiac transplant recipients for angiographically unapparent transplant screening asymptomatic cardiac transplant recipients for angiographically unapparent transplant arteriopathy. However, more studies on the feasibility and safety of this technique in heart transplant arteriopathy. However, more studies on the feasibility and safety of this technique in heart transplant patients are needed.patients are needed.

In-stent RestenosisIn-stent Restenosis Rate of recurrent restenosis after the first treatment of an ISR can reach up to 80% Rate of recurrent restenosis after the first treatment of an ISR can reach up to 80%

according to clinical and angiographic characteristics. The appearance of ISR according to clinical and angiographic characteristics. The appearance of ISR during the patient’s follow-up means the failure of initial intervention in most cases, during the patient’s follow-up means the failure of initial intervention in most cases, leading to complex treatments with a high cost or risk for the patient (atherectomy, leading to complex treatments with a high cost or risk for the patient (atherectomy, brachytherapy, surgical revascularization)brachytherapy, surgical revascularization)

Many patients with previous revascularization undergo catheterization in order to Many patients with previous revascularization undergo catheterization in order to rule out ISR. Many of them present unspecific symptoms, and non-invasive tests are rule out ISR. Many of them present unspecific symptoms, and non-invasive tests are either inconclusive or not performed. either inconclusive or not performed.

The sole presence of angiographic restenosis frequently motivates new intervention The sole presence of angiographic restenosis frequently motivates new intervention in these patients without clear demonstration of myocardial ischaemia. in these patients without clear demonstration of myocardial ischaemia.

FFR should therefore be considered as the optimum tool in the cathlab to decide FFR should therefore be considered as the optimum tool in the cathlab to decide upon the necessity of reintervention on the one hand or deferral of intervention on upon the necessity of reintervention on the one hand or deferral of intervention on the other in ISR of moderate severity. The use of FFR in patients with moderate ISR the other in ISR of moderate severity. The use of FFR in patients with moderate ISR can safely avoid new complex and expensive revascularization procedures that an can safely avoid new complex and expensive revascularization procedures that an have often unsatisfactory longterm results.have often unsatisfactory longterm results.

Limitations of FFRLimitations of FFR The most fundamental limitation is small-vessel disease distal to the location at The most fundamental limitation is small-vessel disease distal to the location at

which Pd is measured. This can be the case in, eg, diabetes, after successful which Pd is measured. This can be the case in, eg, diabetes, after successful thrombolysis and in diffuse coronary atherosclerosis.thrombolysis and in diffuse coronary atherosclerosis.

In cases of poor response to coronary vasodilators, and other conditions in which In cases of poor response to coronary vasodilators, and other conditions in which the cause of decreased maximum flow is located distal to the epicardial coronary the cause of decreased maximum flow is located distal to the epicardial coronary artery, the value of FFRmyo to detect that disease is limitedartery, the value of FFRmyo to detect that disease is limited

Most studies of FFR have been conducted in specific groups of patients with normal Most studies of FFR have been conducted in specific groups of patients with normal left ventricular function and without LVH. In LVH, the growth of the vascular bed left ventricular function and without LVH. In LVH, the growth of the vascular bed is not proportional to the increase of myocardial muscle mass. As a result, it is is not proportional to the increase of myocardial muscle mass. As a result, it is expected that the cut off value to indicate inducible ischaemia will be higher with expected that the cut off value to indicate inducible ischaemia will be higher with increasing severity of hypertrophy. increasing severity of hypertrophy.

Another limitation is exercise induced spasm, which will be missed because Another limitation is exercise induced spasm, which will be missed because pharmacologically induced hyperaemia in the cathlab in such patients is not pharmacologically induced hyperaemia in the cathlab in such patients is not comparable to exercise induced hyperaemia on the treadmill or bicycle.comparable to exercise induced hyperaemia on the treadmill or bicycle.

Potentially false-negative physiological evaluation could occur in the setting of Potentially false-negative physiological evaluation could occur in the setting of transient vasoconstriction of a stenotic lesion or the microcirculationtransient vasoconstriction of a stenotic lesion or the microcirculation

ConclusionConclusion FFR is lesion-specific index of functional severity of an FFR is lesion-specific index of functional severity of an

epicardial stenosisepicardial stenosis Clearly defined normal and pathological valuesClearly defined normal and pathological values Not dependent on changes in BP, HR, contractility, status of Not dependent on changes in BP, HR, contractility, status of

the microcirculation and collaterals.the microcirculation and collaterals. Easy to obtain in the cathlab.Easy to obtain in the cathlab. A useful tool for guiding interventions and predicting A useful tool for guiding interventions and predicting

outcomeoutcome

RELIABLE INDEX FOR CLINICAL DECISION RELIABLE INDEX FOR CLINICAL DECISION MAKINGMAKING

ACC/AHA Guidelines for Percutaneous Coronary ACC/AHA Guidelines for Percutaneous Coronary

Intervention (JACC Vol. 37, NO. 8, June 2001)Intervention (JACC Vol. 37, NO. 8, June 2001) Recommendations for Intracoronary Physiologic Measurements (Doppler Recommendations for Intracoronary Physiologic Measurements (Doppler

Ultrasound, FFR)Ultrasound, FFR)

Class IIaClass IIa1. Assessment of the physiological effects of intermediate coronary stenoses (30 1. Assessment of the physiological effects of intermediate coronary stenoses (30 to 70% luminal narrowing) in patients with anginal symptoms. Coronary to 70% luminal narrowing) in patients with anginal symptoms. Coronary pressure or Doppler velocimetry may also be useful as an alternative to pressure or Doppler velocimetry may also be useful as an alternative to performing noninvasive functional testing (e.g., when the functional study is performing noninvasive functional testing (e.g., when the functional study is absent or ambiguous) to determine whether an intervention is warranted. absent or ambiguous) to determine whether an intervention is warranted. (Level of Evidence: B)(Level of Evidence: B)

Class IIbClass IIb1. Evaluation of the success of percutaneous coronary revascularization in 1. Evaluation of the success of percutaneous coronary revascularization in restoring flow reserve and to predict the risk of restenosis. restoring flow reserve and to predict the risk of restenosis. (Level of Evidence: (Level of Evidence: C)C)

2. Evaluation of patients with anginal symptoms without an apparent 2. Evaluation of patients with anginal symptoms without an apparent angiographic culprit lesion. angiographic culprit lesion. (Level of Evidence: C)(Level of Evidence: C)

Class IIIClass III1. Routine assessment of the severity of angiographic disease in patients with a 1. Routine assessment of the severity of angiographic disease in patients with a positive, unequivocal noninvasive functional study.positive, unequivocal noninvasive functional study. (Level of Evidence: C) (Level of Evidence: C)