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Page 2 of 9 Van der Merwe et al. Vessel Plus 2019;3:24 I http://dx.doi.org/10.20517/2574-1209.2019.17

making and clinical outcomes [6-13] . These studies also suggested that less than 50% of angiographic
significant lesions were functionally significant and that up to 25% of post-angiography guided-coronary
artery bypass grafting (CABG) targets had no impact of physiological myocardial perfusion, potentially
[14]
risking early graft failure, accelerate native artery disease and late graft failure exacerbation . This review
provides an outline of the principles that guide FFR measurement, the clinical evolution of FFR in CABG
practice, the outcomes of recent investigations that compare FFR-guided and angiography guided CABG
and describe potential alternative technology that may assist in ensuring ongoing improvement in surgical
revascularization outcomes.

FRACTIONAL FLOW RESERVE AS A PHYSIOLOGICAL MEASURE OF CORONARY ARTERY
STENOSIS
FFR measurements usually form part of routine diagnostic radial or femoral access cardiac catheterization
under local anaesthesia [6-13] . A pressure transducer within a fluoroscopically visible guide wire record the
coronary arterial pressure distal to the identified lesion and once in position, facilitate the administration
of a hyperemic stimulus by intracoronary or intravenous vasodilator (usually adenosine) injection.
The mean arterial pressures from the pressure wire transducer and from the guide catheter are then
used to calculate FFR, which is defined as the ratio of the average distal coronary pressure to average
aortic pressure at maximal steady state hyperemia (normal value = 1.0). This equates to expressing the
maximum achievable blood flow across an epicardial coronary stenosis to the maximum achievable blood
flow in the absence of any stenosis. Various anatomical and clinical scenarios [15-24] , which are outlined in
Table 1, potentially influence FFR measurement accuracy that may result in deferral- or over-treatment of
physiologically significant culprit lesions (FFR measurement ratio of 0.8 or less).

THE EVOLUTION OF FFR IN CORONARY ARTERY BYPASS GRAFTING
The indications and procedural recommendation for CABG, which now include minimally invasive-
[25]
and hybrid surgical procedures are well described in contemporary guidelines . CABG of target lesions
more than 50% stenosis were historically performed with the intention of restoring distal perfusion and
[26]
to provide distal protection against native disease progression . Subsets of early FFR-PCI measurement
trials identified that up to 25% of target lesions had no myocardial perfusion improvement post-CABG
with early graft failure, accelerate native artery disease and late graft failure exacerbation considered to be
[14]
unfortunate consequences .
[27]
The well-defined benefits of CABG compared with angiography-guided PCI as reported in the ASCERT ,
[30]
[31]
SYNTAX [28,29] , FREEDOM and BEST trials became subjected to intense scrutiny following the
introduction of FFR and newer generation drug-eluting stent technology. Following the ground-breaking
[6]
[7,8]
DEFER study , which established the basis for FFR-guided PCI investigation, the FAME and FAME II
trials [9,10] introduced the concept of physiological revascularization and reinforced the positive impact of
FFR in PCI of multi-vessel disease, which included decreased repeat revascularization (4.3% in the FFR-
guided group, 17.2% in angiography-guided group, P < 0.001), number of stents (mean 1.9 in FFR-guided
group, mean 2.7 in angiography-guided group) and equivalence in 3-year comparative PCI-procedural costs
($16,792 for FFR-guided group, $16,737 for angiography guided group, P = 0.94). However, after 5 years,
the authors reported no statistically significant difference in the incidence of major adverse cardiac events
(MACE) between FFR-guided and angiography-guided PCI (31% in the angiography-guided group, 28% in
the FFR-guided group, P = 0.31). A functional SYNTAX score of lesions with FFR less than 0.8 reclassified
up to 32% of CABG candidates to lower risk groups treatable with both FFR-guided PCI and CABG as
[13]
opposed to CABG alone . Whether the favorable impact of FFR on PCI outcomes could be translated to
surgical practice, became a subject of intense investigation.