Fractional flow reserve

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Editors-In-Chief C. Michael Gibson, M.S. M.D. and Priyantha Ranaweera, M.D. Beth Israel Deaconess Medical Center, Boston.

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Introduction

While coronary angiography assess the extent and magnitude of fixed coronary stenoses, angiography does not provide functional information. While exercise tolerance testing may provide this functional information, it is notable that in one analysis only a quarter to a third of patients undergoing cardiac catheterization had a preceding stress test. While intervention in a critically narrowed lesion is appropriate, a considerable number of lesions are of “intermediate” severity on coronary angiography. Assessment of fractional flow reserve (FFR) may improve the ability to assess the functinal consequences of a lesion in the cardiac catheterization laboratory [1].

Definition

Fraction of maximal achievable blood flow that can still be maintained to the myocardium despite the presence of a stenosis.

FFR = Pd/Pa ( Pd = pressure distal to the lesion measured by the pressure wire, Pa = pressure at the tip of the guide/catheter)

This measure is a surrogate marker of relative ischemia during exercise.

Basis and concept of FFR

  • During maximal hyperemia the FFR can be calculated by dividing the distal pressure by proximal pressure.
  • Pressure drop across a lesion is proportional to:
    • length of the lesion
    • flow across the lesion.
  • It is inversely related to:
    • square root of the area of the stenosis.
Pressure flow volume relationship--source of image: http://www.teachffr.com/
Ohms law and its application to the hydrolics of blood flow--Source: http://www.teachffr.com/

FFR Vs Coronary flow reserve CFR

The FFR assesse the significance of epicardial stenosis independent of the distal vascular bed, where as the CFR is a measure of the distal vascular bed which may be affected by conditions such as hypertension and diabetes.

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 today[2].

Setting up the equipment

Radi medical systems equipment

  • Open the Radi wire from the packet and flush it with saline. Do not pull it out of the protective tubing.
  • Zero the arterial and distal pressure ports. ( Pa and Pd). (If the pressure tracings need to be displayed in the cardiac cath lab display rather than on the Radi console display, then connect the two connector cables from the Radi console to the cath lab system.)
  • Do ACT ( Do not introduce the guide wire in to the coronary artery until the ACT > 200)
  • After confirming an ACT > 200 secs, equlize the pressure with the Radi wire at the tip of the guide.
  • Cross the lesion with the pre-planned wire. (The Radi wire can be used for lesions that are easy to cross)
  • Obsreve the FFR at rest.
  • Induced coronary hyperemia.
  • Measure FFR
  • Could also perform pull back FFR if use the iv route for drugs.

Delivery of the pressure wire through the lesion

Inducing maximum coronary hyperemia

This can be done either by delivering one or more of ic boluses of adenosine 20 mcg(Peak in 5 seconds), or using 140 mcg/kg/min over two mins intra venously from the antecubital fossa or up to 180 mcg/kg/min intravenously from the femoral vein.

Measuring the FFR

Pressure flow volume relationship--source of image: http://www.teachffr.com/

Different types of tracings

As the lesion progresses in severity, the pressure drops first in diastole, and then both in systole and diastole.

Different degress of stenoses--source of image: http://www.teachffr.com/

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 <70%had FFR >0.75 but 50% of lesions with area stenosis >70% had FFR <0.75) [3].
    • (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 year[4].


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 well[5][6].

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-making[7].

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 significance[8].

A study of 51 patients demonstrated that without measuring FFR, even experienced observers estimated the angiographic severity erroneously in 50%[9].

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 rates[10].

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 territory[11].

  • 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 usual[12].
  • (Note: if time interval >48 h use FFR as usual.)*
    • 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 appearance[13].

FFR following percutaneous coronary intervention

In a study of a multicenter registry, Pijils et al showed that using FFR when stenting produced better outcomes[14].

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[15].

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 [16].

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 [16].

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.

Trouble shooting

Coronary FFR summary

References

  1. Pijls NH (2004). "Optimum guidance of complex PCI by coronary pressure measurement". Heart. 90 (9): 1085–93. doi:10.1136/hrt.2003.032151. PMC 1768417. PMID 15310716. Unknown parameter |month= ignored (help)
  2. Pijls NH, De Bruyne B, Peels K; et al. (1996). "Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses". N. Engl. J. Med. 334 (26): 1703–8. PMID 8637515. Unknown parameter |month= ignored (help)
  3. Briguori C, Anzuini A, Airoldi F; et al. (2001). "Intravascular ultrasound criteria for the assessment of the functional significance of intermediate coronary artery stenoses and comparison with fractional flow reserve". Am. J. Cardiol. 87 (2): 136–41. PMID 11152827. Unknown parameter |month= ignored (help)
  4. Pijls NH, van Schaardenburgh P, Manoharan G; et al. (2007). "Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study". J. Am. Coll. Cardiol. 49 (21): 2105–11. doi:10.1016/j.jacc.2007.01.087. PMID 17531660. Unknown parameter |month= ignored (help)
  5. Berger A, Botman KJ, MacCarthy PA; et al. (2005). "Long-term clinical outcome after fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease". J. Am. Coll. Cardiol. 46 (3): 438–42. doi:10.1016/j.jacc.2005.04.041. PMID 16053955. Unknown parameter |month= ignored (help)
  6. Lindstaedt M, Fritz MK, Yazar A; et al. (2005). "Optimizing revascularization strategies in patients with multivessel coronary disease: impact of intracoronary pressure measurements". J. Thorac. Cardiovasc. Surg. 129 (4): 897–903. doi:10.1016/j.jtcvs.2004.08.036. PMID 15821661. Unknown parameter |month= ignored (help)
  7. Botman KJ, Pijls NH, Bech JW; et al. (2004). "Percutaneous coronary intervention or bypass surgery in multivessel disease? A tailored approach based on coronary pressure measurement". Catheter Cardiovasc Interv. 63 (2): 184–91. doi:10.1002/ccd.20175. PMID 15390344. Unknown parameter |month= ignored (help)
  8. Bech GJ, Droste H, Pijls NH; et al. (2001). "Value of fractional flow reserve in making decisions about bypass surgery for equivocal left main coronary artery disease". Heart. 86 (5): 547–52. PMID 11602550. Unknown parameter |month= ignored (help)
  9. Lindstaedt M, Spiecker M, Perings C; et al. (2007). "How good are experienced interventional cardiologists at predicting the functional significance of intermediate or equivocal left main coronary artery stenoses?". Int. J. Cardiol. 120 (2): 254–61. doi:10.1016/j.ijcard.2006.11.220. PMID 17346818. Unknown parameter |month= ignored (help)
  10. Lindstaedt M, Yazar A, Germing A; et al. (2006). "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". Am. Heart J. 152 (1): 156.e1–9. doi:10.1016/j.ahj.2006.03.026. PMID 16824848. Unknown parameter |month= ignored (help)
  11. De Bruyne B, Pijls NH, Bartunek J; et al. (2001). "Fractional flow reserve in patients with prior myocardial infarction". Circulation. 104 (2): 157–62. PMID 11447079. Unknown parameter |month= ignored (help)
  12. Potvin JM, Rodés-Cabau J, Bertrand OF; et al. (2006). "Usefulness of fractional flow reserve measurements to defer revascularization in patients with stable or unstable angina pectoris, non-ST-elevation and ST-elevation acute myocardial infarction, or atypical chest pain". Am. J. Cardiol. 98 (3): 289–97. doi:10.1016/j.amjcard.2006.02.032. PMID 16860011. Unknown parameter |month= ignored (help)
  13. Koo BK, Kang HJ, Youn TJ; et al. (2005). "Physiologic assessment of jailed side branch lesions using fractional flow reserve". J. Am. Coll. Cardiol. 46 (4): 633–7. doi:10.1016/j.jacc.2005.04.054. PMID 16098427. Unknown parameter |month= ignored (help)
  14. Pijls NH, Klauss V, Siebert U; et al. (2002). "Coronary pressure measurement after stenting predicts adverse events at follow-up: a multicenter registry". Circulation. 105 (25): 2950–4. PMID 12081986. Unknown parameter |month= ignored (help)
  15. De Bruyne B, Manoharan G, Pijls NH; et al. (2006). "Assessment of renal artery stenosis severity by pressure gradient measurements". J. Am. Coll. Cardiol. 48 (9): 1851–5. doi:10.1016/j.jacc.2006.05.074. PMID 17084261. Unknown parameter |month= ignored (help)
  16. 16.0 16.1 Leesar MA, Abdul-Baki T, Akkus NI, Sharma A, Kannan T, Bolli R (2003). "Use of fractional flow reserve versus stress perfusion scintigraphy after unstable angina. Effect on duration of hospitalization, cost, procedural characteristics, and clinical outcome". J. Am. Coll. Cardiol. 41 (7): 1115–21. PMID 12679210. Unknown parameter |month= ignored (help)

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