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Dr. Surinder Singh Hansra

Nanavati Hospital
Mumbai
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° xn normal hearts, the flow of blood to the myocardium is controlled
mainly by constriction and dilatation of the microcirculation (vessels
<400µm in diameter).

° As a stenosis develops, a drop in blood pressure occurs across the

stenotic lesion and the microvessels dilate to compensate for the
reduced distal arterial perfusion pressure, maintaining normal resting
blood flow.

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

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

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




° Angiography depicts coronary anatomy from a planar 2D silhouette of the lumen.

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

° Clinically significant intraobserver and interobserver variability, with differences in

the estimation of stenosis severity approaching 50%

° Major discrepancies between the apparent angiographic severity of lesions and

postmortem histology

° Necropsy and x
studies demonstrate that mechanical interventions exaggerate the

extent of luminal eccentricity by fracturing or dissecting the atheroma

° Limited value in evaluating the functional significance of intermediate coronary

lesions
 


° Oarly investigators tried to measure absolute flow, which however, varies widely between
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
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
a considerable interstudy variability.

° 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
normal reference artery is available.

° 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
coronary stenosis.

° 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 the
supplying artery were normal.

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

° FFR is completely independent of changes in heart rate, blood

pressure, and contractility

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

patient

° xt takes into account the contribution of the collateral flow and,

because there is no need for a normal reference artery, it can be
applied in multivessel disease and for serial lesions within one vessel

° Calculation of FFR by pressure measurements has a sound scientific

basis and has been validated in animals and humans

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




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

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

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

° xn 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
achievable myocardial blood flow rather than by the resting flow.

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

° FFRmyo is defined as maximum myocardial blood flow distal to an epicardial stenosis divided
by its value if no epicardial stenosis were present

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

° FFRcor 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
present).
FFRcor = (Pd-
(Pd-Pw) / (Pa
(Pa--Pw)

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,
however, can also be calculated during diagnostic procedures.

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

° 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. xt describes to
what extent maximum myocardial perfusion is affected by the epicardial coronary stenosis,
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° xt has been convincingly demonstrated that an FFR value < 0.75 discriminates functionally
significant lesions.

° 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
echocardiography, and bicycle exercise testing.

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

° 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.

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

° Pijls et al showed that a cutoff value of 0.75 reliably detects ischaemia-

ischaemia-producing lesions for
patients with moderate coronary stenosis and chest pain of uncertain origin, with a sensitivity
of 88%, specificity of 100%, and diagnostic accuracy of 93%.
 x 

° The use of an infusion catheter is not recommended for coronary pressure
measurement, as unpredictable and significant overestimation of the pressure
gradient may occur, resulting in underestimated FFR readings.
° At present, two FDA-
FDA-approved pressure wire systems are available: Pressure
Analyser (RADx Medical Systems, Sweden) and WaveMap ( olcano Therapeutics
xnc.,
SA). These systems both use .014.014-- in. wire with a pressure sensor located 3
cm proximal to the wire tip, which can be used as a primary angioplasty guidewire.
° Oven though 6F or 7F guiding catheters are recommended for FFR measurement, a
recent study has demonstrated that FFR measurement can also be safely performed
through a conventional 4F diagnostic catheter.
° xntracoronary nitroglycerin and heparin are first administered according to the
standard protocol. Afterwards, the pressure-
pressure-sensing guidewire is zeroed, introduced
into the guiding catheter and advanced to its tip.
° At this point, the equality of the pressures recorded from both pressure-
pressure-sensing
guidewire and guiding catheters is verified.
° The pressure-
pressure-sensing guidewire is then further advanced and positioned at least 2
cm beyond the stenosis. The aortic pressure and distal coronary pressure are
measured continuously by the guiding catheter and pressure-
pressure-sensing guidewire.
° After the pressures stabilise, maximum coronary hyperaemia is induced by either
intracoronary (xC) bolus administration or through continuous intravenous (x )
infusion of vasodilator agent, and FFR is then calculated.
 

  
° 
xC 20 -30µg in RCA
30 -50µg in LCA
100µg / incremental doses (poor responders)
x 140 µg/kg/min

° 2

 x 10-
10-40 µg/kg/min

° Papaverine xC 20mg

° Dipyridamole
 -2

° x





° 

  

° 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.
 x!2x-x]!
° Diagnostic
Ambiguous intermediate¶lesions
xnconclusive or lack of noninvasive tests

° Therapuetic
on--line assessment of PTCA
on
 




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° 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
ischaemia (and consequently should be dilated or bypassed if medical treatment
fails).

° Specific applications in this respect are the intermediate stenosis, identification of

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

° xt has been shown retrospectively that it is safe to defer an intervention when FFR
exceeds 0.75 (DOFOR study)

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° xt has been shown that a high value of FFR after regular balloon angioplasty is
associated with a favourable long term outcome.
° xn 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%,
32%, and 42% in patients with a similar angiographic result but an FFR< 0.90.

° xn 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 with
a much lower clinical event rate (<10% in 2years) than if the procedure had been
performed in these patients.

° xn a recent study, observations were made comparing both pressure measurements

and intracoronary ultrasound (xC
S) side by side to evaluate optimal stent
deployment and an almost perfect correlation was found between optimum stent
deployment according to xC
S criteria and complete disappearance of the pressure
gradient across the stent.
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° The differences between a region with and a region without prior Mx are the mass of viable
myocardium is smaller for a similar degree of stenosis and the infarct-
infarct-related resistive vessel
dysfunction may blunt maximal hyperemic response.

° 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
ischaemia, 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
microvascular function and may still be applied to patients with recent Mx.

° 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 Mx with a ³grey area´ of
FFR measurements of 0.72±
0.72±0.8, with a sensitivity of 82% and specificity of 87%.

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

° FFR guidance for PCx of acute myocardial infarction is a useful, low-

low-cost technique that
results in similar clinical outcomes as primary stenting.
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° xt was believed that in
A 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 patients.
A recent study by Leesar et al. of patients with
A or NSTOMx demonstrated that 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.

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° xidentifying patients with multivessel disease who might benefit from catheter-
catheter-based
treatment instead of surgical revascularisation.

° xf acceptable physiologic assessment criteria are met for all the lesions, catheter-
catheter-based
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.

° xn multivessel coronary disease, it is important to know which particular lesion is

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
so that catheter-
catheter-based treatment of culprit lesions can be performed. Chamuleau et al. showed
that FFR is more useful than single-
single-photon emission computed tomography for clinical
decision--making and risk stratification in patients with multivessel disease.
decision
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° Assist decision-
decision-making in patients with intermediate LMCA disease, in order to determine
whether or not CABG should be performed.

° xf 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.
demonstrated that FFR is a lesion-
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
0.75. xn the 54 patients they studied followed-
followed-up was 29 months the survival rates of 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
No death or acute myocardial infarction occurred in any of the deferred patients.

2 


° xn order to quantify lesion severity in a diffusely affected coronary vessel, a pressure pull-
pull-
back curve is needed. This can be done by withdrawing the pressure-
pressure-sensing guidewire from
a distal to a proximal position very slowly during a steady-
steady-state maximum hyperaemia.

° 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-
so-called pull-
pull-back curve is
extremely useful in guiding spot-
spot-stenting in a vessel with long and diffuse lesions.
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° xn the case of tandem lesions, the haemodynamic significance of each individual lesion is influenced by
the presence of the other lesion.

° 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
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
and humans.

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° Cardiac allograft vasculopathy (CA ) is the major cause of mortality and morbidity after the first year of
heart transplantation.

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

° Casella et al. reported a case in which FFR measurement was used to guide and monitor the results of
coronary balloon angioplasty on a CA patient and the results seem very promising. xn addition, a recent
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
arteriopathy. However, more studies on the feasibility and safety of this technique in heart transplant
patients are needed.
x

x
° Rate of recurrent restenosis after the first treatment of an xSR can reach up to 80%
according to clinical and angiographic characteristics. The appearance of xSR during
the patient¶s follow-
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,
brachytherapy, surgical revascularization)

° Many patients with previous revascularization undergo catheterization in order to

rule out xSR. Many of them present unspecific symptoms, and non
non--invasive tests are
either inconclusive or not performed.

° The sole presence of angiographic restenosis frequently motivates new intervention

in these patients without clear demonstration of myocardial ischaemia.

° 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
the other in xSR of moderate severity. The use of FFR in patients with moderate xSR
can safely avoid new complex and expensive revascularization procedures that an
have often unsatisfactory longterm results.
 Ú
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° The most fundamental limitation is small-

small-vessel disease distal to the location at
which Pd is measured. This can be the case in, eg, diabetes, after successful
thrombolysis and in diffuse coronary atherosclerosis.

° xn 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 artery,
the value of FFRmyo to detect that disease is limited

° Most studies of FFR have been conducted in specific groups of patients with normal
left ventricular function and without L H. xn L H, the growth of the vascular bed
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
increasing severity of hypertrophy.

° Another limitation is exercise induced spasm, which will be missed because

pharmacologically induced hyperaemia in the cathlab in such patients is not
comparable to exercise induced hyperaemia on the treadmill or bicycle.

° Potentially false-
false-negative physiological evaluation could occur in the setting of
transient vasoconstriction of a stenotic lesion or the microcirculation
  
° FFR is lesion-
lesion-specific index of functional severity of an
epicardial stenosis
° Clearly defined normal and pathological values
° Not dependent on changes in BP, HR, contractility, status of
the microcirculation and collaterals.
° Oasy to obtain in the cathlab.
° A useful tool for guiding interventions and predicting
outcome

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