Coronary functional flow reserve (FFR)

# Introduction
In one analysis, only a quarter to a third of patients undergoing cardiac catheterization had a preceding stress test. Also a considerable number of patients show intermediate lesions on coronary angiography. It has been shown that visual estimation alone of a lesion may not asses a lesion adequately. In this environment the FFR has enhanced our armamentarium of lesion assessmentref1.

# Pressure-flow relationship in coronary stenosis

# Basis and concept of FFR

## Ohms law and FFR

# FFR Vs Coronary flow reserve CFR

# FFR - 0.75 threshold/cut off
Pijls, et al. in a landmark study validated the clinical use of FFR against previously used gold standards. For a sensitivity of 90% and a specificity of 100% a threshold of 0.75 was proposed - a value which is widely used todayref2.

# Setting up the equipment

# Delivery of the pressure wire through the lesion

# Inducing maximum coronary hyperemia

# Measuring the FFR

# Different types of tracings

# FFR iv hyperemic pullback

# Using FFR to defer coronary intervention

# Reproducibility of FFR

# FFR correlation with IVUS
- Using FFR as the gold standard for lesion severity, Brigouri et al demonstrated
Optimal sensitivity (sens) and specificity (spec) of IVUS to discriminate significant from non-significant stenoses when area stenosis was >70% (sen 100%, spec 68%)
cut-off values fitted to a FFR of <0.75
MLD <1.8 mm (sen 100%, spec 66%),
MLA <4.0 mm2 (sens 92%, spec 56%)
(All lesions with area stenosis 0.75 but 50% of lesions with area stenosis >70% had FFR <0.75) ref3.
(FFR was used as the gold standard in this study.)
- Optimal sensitivity (sens) and specificity (spec) of IVUS to discriminate significant from non-significant stenoses when area stenosis was >70% (sen 100%, spec 68%)
- cut-off values fitted to a FFR of <0.75
MLD <1.8 mm (sen 100%, spec 66%),
MLA <4.0 mm2 (sens 92%, spec 56%)
- MLD <1.8 mm (sen 100%, spec 66%),
- MLA <4.0 mm2 (sens 92%, spec 56%)
- (All lesions with area stenosis 0.75 but 50% of lesions with area stenosis >70% had FFR <0.75) ref3.
- (FFR was used as the gold standard in this study.)

# FFR - correlation with myocardial perfusion

# FFR - correlation with magnetic resonance imaging (perfusion)

# FFR  correlation with CT angiography

# FFR in clinical decision making
In a 5 year followup, it was shown that a non-ischemic stenosis as determinted by FFR assesement could be safely managed medically as there was no symptomatic or prognostic benefit. The death and myocardial infarction rate was <1% per yearref4.

# FFR in multi vessel coronary artery disease (CAD)
In patient with multivessel CAD, using FFR was not only shown to be superior to conclusions based on coronary angiography alone, but safe as wellref5 ref6.
It has been shown that the decisions on management of multivessel coronary artery disese based on coronary angiography alone could both over and undertreat. FFR changed decision in 36% of cases with respect to coronary artery bypass Vs percutaneous coronary angioplasty. The study also showed that additionally FFR also optimized the operative strategy.
Unnecessary bypass surgery may be able to be avoided when FFR is used for decision-makingref7.

# FFR in left main coronary artery disease (LMCA)
In a study of 54 patients, it was shown that the FFR was used effectively in deferring surgical intervention of intermediate left main stenoses if the stenosis had no physiological significanceref8.
A study of 51 patients demonstrated that without measuring FFR, even experienced observers estimated the angiographic severity erroneously in 50%ref9.
In a small study of 51 patients, FFR measurenet was helpful to identify patients with intermediate left main disease in whom deferral of surgical revascularization was associated with excellent survival and low event ratesref10.

# FFR in acute coronary syndromes
The use of FFR has been validated in patients with previous myocardial infarction. The same study also demonstrated the relation between stenosis severity, coronary blood flow, myocardial ischemia, and extent of perfusion territoryref11.
- Recommendations from Eindhoven and Aalst
Acute chest pain without ECG changes or enzyme elevation: FFR applicable as usual.
In  patients with acute chest pain with ECG changes or elevated cardiac enzymes / non-STEMI
Single vessel disease or culprit lesion clear from ECG - FFR indicated, treat culprit. Use FFR, if indicated, in case of other lesions.
If culprit lesion is not clear - use FFR as usualref12.
- Acute chest pain without ECG changes or enzyme elevation: FFR applicable as usual.
- In  patients with acute chest pain with ECG changes or elevated cardiac enzymes / non-STEMI
Single vessel disease or culprit lesion clear from ECG - FFR indicated, treat culprit. Use FFR, if indicated, in case of other lesions.
If culprit lesion is not clear - use FFR as usualref12.
- Single vessel disease or culprit lesion clear from ECG - FFR indicated, treat culprit. Use FFR, if indicated, in case of other lesions.
- If culprit lesion is not clear - use FFR as usualref12.
- (Note: if time interval >48 h use FFR as usual.)*
STEMI/transmural myocardial infarction: FFR  Do not apply in < 5 days.
- STEMI/transmural myocardial infarction: FFR  Do not apply in < 5 days.
FFR in lesions involving bifurcations and sidebranches.
In this study, measurement of FFR in jailed side branch lesions was shown to be both safe and feasible. It also showed that most of these lesions did not have functional significance, despite morphologic appearanceref13.

# FFR following percutaneous coronary intervention
In a study of a multicenter registry, Pijils et al showed that using FFR when stenting produced better outcomesref14.

# FFR in the era of drug eluting stents

# FFR measurement in renal artery stenosis
Using PressureWire and vasodilatory stimulus, and during diagnositc catheterization, pressure measurement and calculation of Pd/Pa ratio can be used to guide treatment of renal artery stenosis. The cutoff value is found to be a Pd/Pa ratio of 0.90 ref15.

# FFR and overall time saved
Using FFR for decision making was shown to cut down the overall hospital stay with better outcomes when compared to using angiography alone to guide angiographic findings ref16.

# FFR and cost
Using FFR for decision making was shown to cut down the overall cost with better outcomes when compared to using angiography alone to guide PCI ref16.

# Precautions
- Ensure that there is no pressure gradient between the pressure wire (placed at the tip of the guide) and the guiding catheter. The pressures should be equalized at the onset.
- The two pressures should be compared and noted before inducing coronary hyperemia.
- Use a standard wire first to cross difficult lesions. The pressure wire may not be the most suitable in complex lesions.
Eg.
Pressure wire may track under a plaque and cause a dissection.
Repeated attempts in trying to negotiate tortuous anatomy may cause trauma to intact endothelium and promote thrombosis and dissection.
- Eg.
Pressure wire may track under a plaque and cause a dissection.
Repeated attempts in trying to negotiate tortuous anatomy may cause trauma to intact endothelium and promote thrombosis and dissection.
- Pressure wire may track under a plaque and cause a dissection.
- Repeated attempts in trying to negotiate tortuous anatomy may cause trauma to intact endothelium and promote thrombosis and dissection.

# Trouble shooting

# Uses of FFR  summary
ref18.

# Back to main pge
- ref1 Pijls, et al, Optimum Guidance by coronary pressure measurement; Heart 2004, 90:1085-1093
- ref2 Pijils, et al. Measurement of fractional fl ow reserve to assess the functional severity of coronaryartery stenoses; New England Journal of Medicine 1996:334;26:1703-8.
- ref3 Brigouri, et al. Intravascular Ultrasound Criteria for the Assessment of the Functional Signifi cance of Intermediate Coronary Artery Stenoses and Comparison With Fractional Flow Reserve, American Journal of Cardiology 2001:87:136-141.
- ref4 Pijls, et al. Percutaneous coronary intervention of functional nonsignificant stenosis: 5-year follow-up of the DEFER study. The Journal of the American College of Cardiology
- ref5 Berger, et al. Long-Term Clinical Outcome After Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease, Journal of the American College of Cardiology 2005:3:438-42.
- ref6 Lindstaedt, et al. Optimizing revascularization strategies in patients with multivessel coronary disease: impact of intracoronary pressure measurements. J Thorac Cardiovasc Surg 2005:129;4:897-903.
- ref7 Botman, et al. Percutaneous Coronary Intervention or Bypass Surgery in Multivessel Disease? A Tailored Approach Based on Coronary Pressure Measurement. Cathet Cardiovasc Intervent 2004:63:184-191.
- ref8 Bech et al.  Value of fractional fl ow reserve in making decisions about bypass surgery for equivocal left main coronary artery disease; Heart 2001:86:547-552.
- ref9 Lindstaedt, et al. How good are experienced interventional cardiologists at predicting the functional signifi cance of intermediate or equivocal left main coronary artery stenoses?; International Journal of Cardiology, In Press, Corrected Proof, Available online 7 March 2007.
- ref10 Lindstaedt, et al., Clinical outcome in patients with intermediate or equivocal left main coronary artery disease after deferral of surgical revascularization on the basis of fractional  flow reserve measurements; American Heart Journal 2006,152:156.
- ref11 De Bruyne, et al. Fractional Flow Reserve in Patients With Prior Myocardial Infarction, Circulation 2001, 104:157-162.
- ref12 Potvin, et al., Usefulness of Fractional Flow Reserve Measurements to Defer Revascularization in Patients With Stable or Unstable Angina Pectoris, NonST-Elevation and ST-Elevation Acute Myocardial Infarction, or Atypical Chest Pain, American Journal of Cardiology, 2006, 98:289-297.
- ref13 Koo, et al., Journal of the American College of Cardiology 2005, 46;4:633-7. Physiologic Assessment of Jailed Side Branch Lesions Using Fractional Flow Reserve
FFR
- ref14 Pijls, et al., Coronary Pressure Measurement After Stenting Predicts Adverse Events at Follow-Up. Circulation 2002:105:2950-2954.
- ref15 De Bruyne, et al., Assessment of Renal Artery Stenosis Severity by Pressure Gradient Measurements; Journal of the American College of Cardiology 2006 48:1851-1855.
- ref16 Leesar, et al. Use of fractional flow reserve versus stress perfusion scintigraphy after unstable angina. Effect on duration of hospitalization, cost, procedural characteristics, and clinical outcome. Journal of the American College of Cardiology2003, 41;7:1115-21 ref17.
- ref17 Wongpraparut, et al. Thirty-Month Outcome After Fractional Flow Reserve-Guided Versus Conventional Multivessel Percuraneous Coronary Intervention; American Journal of Cardiology 2005:96;7:877-84 .
- ref18 Kern M, et al; Circulation. 2006;114:1321-1341; Physiological Assessment of Coronary Artery Disease in the Cardiac Catheterization Laboratory. A Scientifi c Statement From the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology