Guiding PCI with fractional flow reserve (FFR)

Guiding PCI with fractional flow reserve (FFR)

Coronary angiography gives a visual impression about the severity of the stenosis. But it need not imply the actual functional significance of the stenosis in terms of flow physiology. It is often difficult to decide which are the flow limiting lesions when there are multiple stenoses in same or different territories. It is here that the fractional flow reserve estimation helps. Fractional flow reserve (FFR) is estimated using a guide wire with a pressure transducer. Current FFR wires have properties similar to the floppy guide wires so that they can passed across coronary lesions back and forth easily to assess the pressure drop across the lesions. The flow reserve is calculated after inducing maximal hyperemia in the distal territory with intracoronary adenosine or papaverine or intravenous adenosine given in a central vein. FFR is obtained by dividing the pressure distal to the stenosis by the central aortic pressure, which is usually equal to the pressure proximal to the stenosis if there is no additional stenosis in between. Normal FFR is 1.0 and an FFR below 0.75 indicates inducible ischemia while an FFR above 0.80 excludes ischemia in 90% of cases. So it is evident that the grey zone in FFR evaluation is very limited. FFR measurement is successful in almost 99% of cases and the values are reproducible. If the FFR normalizes after stenting, the restenosis rates at six months is less than 5%. Since the FFR wire can be used for guiding balloon catheters and stents, it is easy to make post procedure measurements without any additional effort. When there are multiple stenosis, the wire will pick up the pressure drop at each lesion so that we can decide on which all lesions are significant and needs tackling.

A study [1] evaluated the two year results of FFR guided PCI (percutaneous coronary intervention). They reported the two year follow up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study which had shown that FFR improves the outcome of PCI at one year [2]. The study involved over one thousand patients with multi vessel coronary artery disease randomized to PCI with either angiographic guidance alone or with FFR in addition. In the angiography alone guided group, the decision for stent was depending on the visual appearance of the lesion. In the FFR guided group, stents were deployed only for the lesions which showed and FFR of 0.80 or less. The other lesions were left on medical management. Naturally the FFR guided group received lesser number of stents. They had lower rates of mortality or myocardial infarction. PCI or coronary artery bypass surgery rates were also lower, though not statistically significant. The lesions deferred on basis of FFR had only a 0.2% myocardial infarction rate and 3.2% revascularization rate. A downside of the study was that it had included lesions of 50 to 79% stenosis also. But the authors justify their decision mentioning that 35% of these lesions were hemodynamically significant and leaving them untreated based on angiographic appearance alone would not have been ideal. Another potential draw back of the data is that theoretically the lesions left alone based on FFR can also progress beyond the study period of two years and present later with significant stenosis.

FAME 2 study randomized 1220 patients with stable coronary artery disease and angiographically significant stenoses in whom at least one stenosis had FFR 0.8 or less. They were assigned to either FFR guided PCI plus medical therapy or medical therapy alone [3]. FFR guided PCI was associated with significantly lower rate of primary composite end point of death, myocardial infarction or urgent revascularization at 5 years than medical therapy alone. Those without hemodynamically significant stenosis who were entered in a registry, had a favorable long term outcome with medical therapy alone.

Reference

1. Pijls NH, Fearon WF, Tonino PA, Siebert U, Ikeno F, Bornschein B, van’t Veer M, Klauss V, Manoharan G, Engstrøm T, Oldroyd KG, Ver Lee PN, MacCarthy PA, De Bruyne B; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol. 2010 Jul 13;56(3):177-84. 
2. Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van’ t Veer M, Klauss V, Manoharan G, Engstrøm T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009 Jan 15;360(3):213-24.
3. Xaplanteris P, Fournier S, Pijls NHJ, Fearon WF, Barbato E, Tonino PAL, Engstrøm T, Kääb S, Dambrink JH, Rioufol G, Toth GG, Piroth Z, Witt N, Fröbert O, Kala P, Linke A, Jagic N, Mates M, Mavromatis K, Samady H, Irimpen A, Oldroyd K, Campo G, Rothenbühler M, Jüni P, De Bruyne B; FAME 2 Investigators. Five-Year Outcomes with PCI Guided by Fractional Flow Reserve. N Engl J Med. 2018 Jul 19;379(3):250-259.