Figure 7.9 Examples of cases in which low FFR values are generated by high magnitudes of hyperaemic flow. In both cases, baseline instantaneous wave‐free ratio (iFR), coronary flow velocity reserve (CFVR) and hyperaemic stenosis resistance index (HSR) were normal, indicating a mild, not flow‐limiting stenosis. In (B) a SPECT myocardial perfusion scan also confirms the absence of myocardial ischaemia. In these cases, hyperemic pressure is not reflecting flow and is not representative of ischaemia. Adapted from Petraco et al (2014).
In patients with left main stem stenoses, there is longer‐standing data to support decision making with FFR. Recent studies have shown similar outcomes in those managed by iFR [80]. For both parameters, study design constraints prevent a definitive answer outside a dedicated randomized study.
Resting indices are particularly helpful in serial stenoses; this extends to discerning hemodynamic significance of stenoses separated by diffuse disease. Both approaches permit mapping coronary vessels, but resting indices have less flow interaction meaning post‐PCI results are more predictable.
Does discrepancy matter?
When both iFR and FFR are measured, a mismatch is possible in 1 in 5 cases of truly moderate disease. This is less likely in truly severe and truly mild stenoses. To date, there is no randomized data for this subset of patients, but close observational studies have suggested there is no difference in event rates when resting indices are negative and FFR is positive; the event rate is the same as seen when all the indices are negative [88]. A higher event rate has been demonstrated when all the indices are ischemic and the vessels are deferred [88].
In the setting of a mismatch, there are three basic clinical options: (i) treat according to the most positive index, (ii) treat according to the most negative index, (iii) use other data to act as an arbiter for clinical decision‐making.
In the case of option (i) future events will likely be driven by the quality of the stented segment; therefore, any treatment should be performed at the highest possible quality. Imaging should be used to support the intervention and ensure maximum lumen area is achieved. Post‐stenting physiology is advisable to ensure a genuine physiological gain is achieved; if there is no appreciable gain, then this suggests that the difference between the two parameters was not solely due to the lesion being assessed.
If option (ii) is chosen and the lesion is deferred, then escalated medical therapy and close observation would be appropriate. If there are ongoing symptoms or if quality of life is reduced, PCI still remains a viable option.
If (iii) is pursued, then other clinical parameters and patient symptoms should be considered for decision making. Occasionally, intravascular imaging may be helpful to evaluate for plaque instability, very large plaque burden or significantly decreased minimal lumen area.
In all cases, one should recall that the index is not an arbiter of clinical medicine and is used to supplement clinical decision making. The issue of mismatch dichotomy has resulted from the need of hard cut‐points during the index development. One should recall that there is no true hard point of “ischemia” – rather it is a continuum which should be treated as such.
Physiology after PCI
Physiological indices can provide an assessment of the success of coronary intervention. Both FFR or NHPR may be used to assess the hemodynamic improvement after a stent. Theoretically, complete removal of coronary stenoses should result in an iFR or FFR of 1.0. This is rarely the case as there is often milder focal or diffuse disease. A concern can be that treating a stenosis can “unmask” the physiological importance of residual stenoses due to “crosstalk” between stenoses. A further concern can be that PCI can cause acute microvascular dysfunction such that post‐PCI physiology may under‐estimate the significance of residual disease (by blunting response to adenosine). Furthermore, for resting indices, the process of balloon inflation or stent deployment generates relative ischemia and submaximal hyperemia that will cause a resting index to appear more ischemic. In practice, the time taken to remove the interventional balloons, flush the catheters, re‐administer intracoronary nitrates and prepare the pressure wire to make a measurement, there is stabilization of the physiological states that permit both iFR and FFR to be measured.
FFR after PCI
Fractional flow reserve has been assessed after coronary intervention in a number of studies. Post‐PCI FFR values below 0.90 predict a less favorable clinical outcome in an early PCI era [31,89]. Some of the post‐PCI studies were in a period of balloon angioplasty with stenting only used for bailout [31]. Subsequent studies in the DES era have similarly demonstrated a higher event rate in those patients in whom post‐PCI FFR is not optimal; there is consistent evidence for increased rates of target vessel failure and target vessel revascularization when FFR falls within lower tertiles or quartiles [25–27,29,32]. While individual studies do not have sufficient power to show higher rates of mortality and myocardial infarction, meta‐analysis has shown both are predicted by low FFR values post‐PCI [30,31]. Data collated from large randomized studies show the greatest clinical benefit is seen in patients with the largest gain in FFR [28]. Post‐PCI resting whole cycle Pd/Pa has also been shown to predict MACE events after intervention with values over 0.96 representing a more favorable result [90].
The frequency of an inadequate physiological result is more common than appreciated. Large studies have suggested that an FFR ≤0.80 can occur in 10–20% of cases suggesting a suboptimal interventional result [29,32].
A single focal stenosis without residual disease is expected to achieve a high post‐PCI FFR value. Those lesions with moderate or high burdens of residual disease, then lower post‐PCI FFR values are expected. However, the same limitations of angiography that exist prior to intervention, continue to impact assessment after PCI and can mean residual disease is under‐estimated. It is recommended that FFR is repeated after PCI and careful pullback measurement is made to assess the cause of residual pressure loss.
In some circumstances, the vessel remains ischemic and, in this setting, this can reflect: (i) the incorrect coronary stenosis has been targeted, (ii) there is an issue within the stented segment, or (iii) diffuse coronary atherosclerosis that was not amenable to treatment with a focal stent.
NHPR after PCI and the DEFINE‐PCI study
IFR can detect the pressure change achieved by coronary intervention but there is no clear established cut‐point that predicts later MACE [49]. During routine PCI, there is detectible change in pressure gradients without a significant change in resting coronary blood flow; this is true for the majority of moderate or severe stenoses [45]. As resting flow does not change significantly, residual pressure gradients do not change significantly. This means that changes in coronary pressure can be predicted before coronary intervention is undertaken and this has been shown in both small [22] and large studies [23]. The level of prediction is good but there are limits and this becomes evident when very severe stenoses are involved; those lesions in which the potential gain is greater than 0.40 iFR units, there can be change in resting flow conditions such that there is change to the pressure‐flow relationships within the vessel which alters the residual pressure gradients. In this situation, the pre‐PCI prediction may be less accurate. [45]. However, for the majority of lesions in which pressure wires are used, this is less of an issue.
In this context, the DEFINE‐PCI study [91] assessed
