The Challenge

Coronary angiography, the standard method for determining which lesions in a patient with complex coronary artery disease should be stented, provides a two-dimensional view of the lesion. Imaging/morphologic modalities such as angio, CT and IVUS cannot identify which individual lesion(s) are the cause of the patient's ischemia. These imaging modalities can both under- and overestimate lesion severity, either leaving significant lesions untreated or causing excess stenting. In contrast to FFR, which is a physiological modality, imaging modalities do not take into account collateral flow or abnormal/impaired myocardium. Non-invasive tests, when performed, are often inconclusive and do not give the physician detailed information needed to pinpoint the specific lesion. Studies have shown that stenting of lesions that are not responsible for ischemia is unnecessary and may actually worsen outcomes, increasing both costs and risk to the patient.¹

 

The Solution

Fractional Flow Reserve (FFR) is a pressure derived, lesion specific, physiological index determining the hemodynamic severity of intracoronary lesions. FFR is measured by placing a pressure guidewire across the lesion of interest and pharmacologically inducing hyperemia. The ratio of distal to proximal pressure allows the physician to physiologically determine if the narrowing is the cause of ischemia. As shown by the FAME study, using FFR the operator can guide intervention to the lesions responsible for the patient’s symptoms, leading to significantly improved clinical outcome and reduced procedure cost, without prolonging the procedure.

 

Clinical Evidence

Fractional Flow Reserve Versus Angiography for Guiding Percutaneous Coronary Intervention (FAME)

Published in The New England Journal of Medicine, the landmark FAME study demonstrates that the use of FFR reduces major adverse cardiac events (MACE) including death, myocardial infarction and repeat revascularization, and makes stent placement safer, more efficient and more cost-effective.² The prospective, multicenter trial comprised 1,005 patients with multivessel coronary artery disease randomized to either angiographically driven percutaneous coronary intervention or fractional flow reserved guided revascularization. To read more about the FAME study, visit www.famestudy.com.

Outcomes

Compared to angiography-only procedures, FAME shows that FFR:

• Significantly reduced the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at one year
• Significantly reduced the combined rate of death and myocardial infarction
• Significantly lowered procedure-related costs
• Significantly decreased the amount of contrast agent used
• Results in similar, if not improved, functional status with no decrease in health-related quality of life
• Did not prolong procedure time

Absolute Difference in MACE-free Survival

 

 

MACE

 

 

Costs and Equipment Use

 

^1,2Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213-224.

Case Studies

Case study 1: FFR in multivessel disease

• 59-year-old male
• No specific cardiac history
• End stage liver failure
• Referred to determine eligibility for liver transplant

LAD

Angiography showed three diseased vessels. FFR helped to identify which lesions required treatment. A pressure pullback in the long disease segment of the LAD revealed that there was no significant reduction in flow in this vessel (FFR >0.75). 

LCX

The FFR in the LCX was below 0.75 and a pressure pullback recording showed both lesions to be significant. Two stents were placed satisfactorily as confirmed by FFR >0.90.

 RCA

The FFR in the RCA was well below 0.75. The most proximal stenosis was stented first and a new FFR measurement was performed. A continued low FFR prompted stenting of the distal lesion as well.

Thanks to FFR this patient was steered away from CABG and the satisfactory post-stent FFR results mean a good prognosis for this patient.

Case courtesy of Michael Lim, M.D., FSCAI.  

1. Pijls NH, De Bruyne B, Peels K, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med. 1996;334(26):1703-1708.
2. Pijls NH, De Bruyne B, Bech GJ, et al. Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery: validation in humans. Circulation. 2000;102(19):2371-2377.
3. Pijls NH, Klauss V, Siebert U, et al. Coronary pressure measurement after stenting predicts adverse events at follow-up: a multicenter registry. Circulation. 2002;105(25):2950-2954.
   
   

Further reading

• Botman KJ, Pijls NH, Bech JW, et al. Percutaneous coronary intervention or bypass surgery in multivessel disease? A tailored approach based on coronary pressure measurement. Catheter Cardiovasc Interv. 2004;63(2)184-191.
• Jiménez-Navarro MF, Alonso-Briales J, Hernández-Garcia JM, et al. Usefulness of fractional flow reserve in multivessel coronary artery disease with intermediate lesions. J Interv Cardiol. 2006;19(2):148-152.
• Wongpraparut N, Yalamanchili V, Pasnoori V, et al. Thirty-month outcome after fractional flow reserve-guided versus conventional multivessel percutaneous coronary intervention. Am J Cardiol. 2005;96(7):877-884.
• Berger A, Botman KJ, MacCarthy PA, et al. Long-term clinical outcome after fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease. J Am Coll Cardiol. 2005;46(3):438-442.
• Lindstaedt M, Fritz MK, Yazar A, 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.

Case study 2: FFR in sidebranches 

• 47-year-old male
• Atypical chest pain
• No stress testing performed
• Referred for repeat angiography

Angio shows a suspicious stenosis in the diagonal brach and mild disease in the RCA.

LAD

An FFR measurement of 0.87 in the diagonal branch—well above the ischemic threshold—showed that this lesion was most likely not the cause of ischemia and could safely be left alone.

 RCA

Utilizing a long-lasting I.V. hyperemic stimulus, the pullback measurement across the mild-looking long lesion in the RCA displayed a significant jump in the midsection, identifying a severe, flow-limiting lesion.

The results revealed that it was unnecessary to stent the diagonal branch and that the patient could instead be helped by one stent placed in the RCA. Angiographic findings are often discordant with the actual physiologic importance. Stenting of ostial lesions is not without risk and therefore it must be certain it is necessary.

Case courtesy of Michael Lim, M.D., FSCAI. 

1. Pijls NH, De Bruyne B, Peels K, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med. 1996;334(26):1703-1708.
2. Pijls NH, De Bruyne B, Bech GJ, et al. Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery: validation in humans. Circulation. 2000;102(19):2371-2377.

Further reading:

• Koo BK, Kang HJ, Youn TJ, et al. Physiologic assessment of jailed side branch lesions using fractional flow reserve. J Am Coll Cardiol. 2005;46(4):633-637.
• Bellenger NG, Swallow R, Wald DS, et al. Haemodynamic significance of ostial side branch nipping following percutaneous intervention at bifurcations: a pressure wire pilot study. Heart. 2007;93(2):249-250.

Case study 3: FFR in left main disease

• 66-year-old male
• Slowly progressive dyspnea over the past 18 months during exercise
• Newly occurring retrosternal burning sensation prompted coronary catheterization in a referring hospital

LAD

The patient was initially referred for bypass surgery based on the coronary angiograms. An FFR measurement of 0.69 in the distal LAD indicated inducible ischemia. Upon pullback of the pressure wire, a localized pressure drop occurred at the exact location of the proximal LAD stenosis. Proximal of the lesion, the FFR was 0.95.

 LCX

The FFR measured in the LCX was 0.93, excluding a hemodynamically significant left main stenosis.

The patient was treated by PCI with stenting of the proximal LAD and angioplasty of the first diagonal. The post-interventional FFR measurement was 0.87 in the distal LAD with no further pressure drops upon pullback. By using FFR, a LM stenosis could be excluded and unnecessary bypass surgery was avoided and the patient was successfully treated by PCI. At follow-up, the patient reported almost full recovery of his exercise capacity.

Case courtesy of Michael Lindstaedt, M.D.  

1.  Pijls NH, De Bruyne B, Peels K, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med. 1996;334(26):1703-1708.
2. Pijls NH, De Bruyne B, Bech GJ, et al. Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery: validation in humans. Circulation. 2000;102(19):2371-2377.
3. Pijls NH, Klauss V, Siebert U, et al. Coronary pressure measurement after stenting predicts adverse events at follow-up: a multicenter registry. Circulation. 2002;105(25):2950-2954.
4. De Bruyne B, Hersbach F, Pijls NH, et al. Abnormal epicardial coronary resistance in patients with diffuse atherosclerosis but “Normal” coronary angiography. Circulation. 2001;104(20):2401-2406.

Further reading:

• Bech GJ, Droste H, Pijls NH, et al. Value of fractional flow reserve in making decisions about bypass surgery for equivocal left main coronary artery disease. Heart. 2001;86(5):547-552.
• Leesar MA, Masden R, Jasti V. Physiological and intravascular ultrasound assessment of an ambiguous left main coronary artery stenosis. Catheter Cardiovasc Interv. 2004;62(3):349-357.
• Botman CJ, Arnoudse W, Penn O, et al. Long-term outcome after surgical left main coronary angioplasty. Ann Thorac Surg. 2006;81(3):828-834.
• Lindstaedt M, Yazar A, Germing A, 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. Am Heart J. 2006;152(1):156.e1-9. 
•  Lindstaedt M, Spiecker M, Perings C, et al. How good are experienced interventional cardiologists at predicting the functional significance of intermediate or equivocal left main coronary artery stenoses? Int J Cardiol. 2007;120(2):254-261.
• Botman CJ, Post H, Penn O, et al. Value of magnetic resonance imaging, angiography, and fractional flow reserve to evaluate the left main coronary artery after direct surgical angioplasty. Ann Thorac Surg. 2007;83(2):490-494.
• Pijls NH, Bech GJ, De Bruyne B, et al. Clinical assessment of functional stenosis severity: use of coronary pressure measurements for the decision to bypass a lesion. 1997;63(6 Suppl):S6-11.