Fractional flow reserve after previous myocardial infarction

Marques and colleagues have conducted an interesting study on microvascular resistance of viable tissue within an infarcted area.1 This study is important, not only from a conceptual point of view, but also because it has several relevant implications for the applicability of MIBI spect and fractional flow reserve (FFR) measurement in patients with previous myocardial infarction and a residual or recurrent stenosis in the infarct-related coronary artery. The use of these methods, one non-invasive and the other invasive, has been supported by theoretical and empirical data, but the present study corroborates their usefulness in patients with previous myocardial infarctions. To understand the clinical implications of the study by Marques et al., it is paramount to understand microvascular resistance, which so far has been hard to assess in conscious humans. Microvascular resistance equals the ratio of distal coronary pressure divided by myocardial blood flow. As surrogates for the numerator and denominator of that ratio, sometimes aortic pressure and coronary blood flow or flow velocity, respectively, have been used, which might be correct in healthy persons. However, in patients with coronary artery disease, the first number overestimates distal coronary pressure and the second one underestimates myocardial blood flow, and therefore use of these surrogates leads to progressive overestimation of myocardial resistance in the case of a stenotic coronary artery.2–4 As a consequence, our knowledge about microvascular resistance in patients with coronary disease, and especially after previous myocardial infarction, has remained questionable. Furthermore, from a clinical point of view, i.e. the question of whether inducible ischaemia is still present or present again, the interesting index to study is hyperaemic blood flow, corresponding to minimal resistance of the viable myocardium within the infarcted zone, not the resistance of the scar tissue. As positron emission tomography, used by Marques et al., only measures blood flow in viable tissue, this latter value, combined with distal coronary pressure measured by the pressure wire, provides the opportunity for correct assessment of microvascular resistance of viable tissue within the infarcted area.1 FFR is considered as the gold standard for invasive assessment of inducible ischaemia.5,6 It has been validated in a wide variety of clinical conditions and it has been shown empirically by de Bruyne et al. and Usui et al. that the generally used threshold of ischaemia of 0.75–0.80 remains valid after previous myocardial infarction.7,8 This is understandable from theory, but not so trivial, and in this respect the study of Marques et al. is especially helpful. To clarify this issue, in Figure 1 the stenotic epicardial coronary artery and its dependent perfusion territory are depicted. Although viable areas and scar tissue will most probably be scattered and patchy,9 for the sake of simplicity the necrotic tissue is represented in Figure 1 by the shaded area and the viable myocardium by the clear area. In the upper half of the figure, before infarction occurred, there is a significant epicardial stenosis resulting in an FFR of 0.60 in this example. After the infarction, part of the perfusion territory has become necrotic, which means that maximum blood flow to the total territory has decreased, meaning that (even if the epicardial stenosis would remain unchanged) FFR has increased. Simplified illustration of a stenotic epicardial coronary artery and its dependent perfusion territory, before (upper part) and after myocardial infarction (lower part). Because of the large extent of the perfusion area and associated high value of maximum blood flow in the upper part of the figure, a particular anatomic stenosis will result in a large pressure gradient and low fractional flow reserve (FFR), e.g. 0.60 in this example. After myocardial infarction (when part of the perfusion territory has become necrotic and the viable area within the perfusion territory is smaller), despite a similar hyperaemic response of that viable part of the myocardium, maximum achievable blood flow in the supplying artery will be lower and FFR increases even if the severity of the stenosis remains the same. In other words, an anatomically identical stenosis results in a higher FFR (and therefore is less significant from a functional point of view) if the (viable) perfusion area of the artery decreases. This indicates that the physiological significance of the stenosis has decreased, not by a morphological change of the stenosis itself but by a decrease of the perfusion territory. Also, in contrast to anatomy-based approaches, FFR can still be used to assess this physiological significance reliably. What does this mean? At first glance, this observation might question the applicability of FFR after previous myocardial infarction. At a second glance, however, it is clear that the haemodynamic significance of the (anatomically unchanged) stenosis has decreased because the perfusion territory has decreased to a similar degree. It is only the remaining viable myocardium which has to be perfused, meaning that from a physiological point of view, the stenotic epicardial coronary artery is no longer significantly narrowed despite unchanged morphology. In other words, even if the severity of the anatomic stenosis and the stenosis resistance remain unchanged, its physiological severity decreases, due to a decrease in the amount of viable myocardium dependent on that artery. Therefore, the increase of FFR from 0.60 to 0.80 correctly indicates that this stenosis would be significant before the infarction but not afterwards. In fact, FFR accounts for the complex inter-relationship between anatomic stenosis severity, myocardial blood flow, extent of the perfusion area, and inducible ischaemia. It is a quite unique index in this way. In contrast, it is also easy to understand now why after a previous infarction, a particular value of FFR corresponds to the average value of a more severe stenosis, as was the case before infarction.10 Although this sounds somewhat complex, it can be understood easily by making the comparison with a field of corn irrigated by a water pipe which is originally wide enough to supply the field with sufficient water. If the water pipe becomes narrowed for one reason or another, it might become insufficient to produce an adequate water supply and part of the field will dry out. Once this has happened, however, the (still narrowed) pipe will be sufficient again to supply enough water to the remaining viable part within the field of corn. In other words, although the anatomy of the water pipe remains unchanged, the haemodynamic significance of its narrowing has decreased because of the decrease of the perfusion area. Also it is clear that when we are interested in the water consumption per square metre of the viable part within that original field of corn, this consumption is identical to that of a nearby field never threatened by lack of water. The study by Marques et al. was performed in patients with chronic myocardial infarction.1 Therefore, caution is warranted in extrapolating their data to an acute or semi-acute infarction when stunning and intramyocardial oedema may be present and when also the perfusion of the non-necrotic tissue might be disturbed. For that reason, it should be emphasized that FFR should not be applied in the first days after transmural myocardial infarction, when a high FFR can be present despite a severe residual stenosis. However, after stunning and oedema have resolved, FFR can be safely applied with a similar threshold value of ischaemia to that in normal patients. It is not possible to predict the exact time interval for doing so because that also depends on the extent of the infarction and probably varies from one person so another. However, from the above-mentioned study by de Bruyne, we know that at least after 5 days, FFR can be applied to assess the physiological significance of a residual or recurrent stenosis in the infarct-related artery.7 Marques et al. mention a few limitations of their study, i.e. non-simultaneous performance of PET and invasive measurement, and a different method of inducing myocardial hyperaemia1 (in one case intravenous adenosine, and in the other intracoronary). However, these are minor issues as the perfusion pressure and hyperaemic rate pressure product remained unchanged and as intracoronary and intravenous adenosine induce hyperaemia to a similar degree.11 Finally, for the myocardial reference areas studied by Marques et al., only a small hyperaemic pressure gradient was present within the supplying coronary artery, indicating that these areas could be used reliably as almost normal reference areas. In conclusion, this elegant study provides more insight into the physiology of viable tissue within an infarcted area and supports the basis of using non-invasive MIBI spect and invasive FFR measurements for reliable assessment of ischaemia after previous myocardial infarction. Conflict of interest: none declared.