COMMENTARY: Broadening the Applications of Fractional Flow Reserve

The concept of fractional flow reserve (FFR) was introduced by Pijls et al in his publication in 1993.¹ This concept uses pressure measurement as a surrogate for flow, in a state where resistance is minimal and constant, a state of maximal hyperemia. This is usually achieved using intracoronary or intravenous adenosine administration. The ratio of the mean pressure distal to an epicardial coronary stenosis as measured by the pressure-monitoring wire, to the mean proximal pressure, measured as the aortic pressure from the tip of the guiding catheter, is the fractional flow reserve. FFR is a lesion specific, or vessel specific in case of sequential lesions, invasive method to evaluate the hemodynamic significance of epicardial coronary stenoses. This has been well correlated to various modalities of physiologic stress tests, where threshold values for FFR have been established, above which no evidence of inducible ischemia could be seen on noninvasive testing.^2–5 The initial description of this method mentioned certain limitations for its appication, such as cases where maximal hyperemia could not be adequately achieved.1 The paper by De Bruyne, describing the differences between coronary flow reserve (CFR) and FFR excluded patients with left ventricular hypertrophy or diabetes mellitus to avoid the effects of microvascular disease.⁶ Further work by Baumgart et al showed that FFR correlated with relative coronary velocity flow reserve (r CFR), but not with coronary flow reserve (CFR), suggesting that FFR is independent of effects of the microvascular circulation or hemodynamic variations.⁷ But the theoretical concept that severe microvascular disease can significantly impair maximal hyperemia, thus interfering with FFR measurements and limiting its clinical value, remains a concern. The paper by Chhatriwalla et al⁸ in this issue of the Journal examines the effect of potential microvascular disease on the clinical utility of FFR measurements by comparing FFR, for matched epicardial coronary lesions, in patients with a high left ventricular mass index (LVMI) to patients with normal LVMI. Of 112 consecutive patients who underwent angiography and FFR measurement, 22 patients with increased LVMI were matched to 62 patients with normal LVMI for minimal lumen diameter, percent diameter stenosis, and lesion length. LVM was measured using a modification of the Rackley method from ventriculography. The authors further validated their LVM calculations using this method by comparing it to magnetic resonance imaging, in a separate cohort of patients, with good correlation. There was a significant correlation between FFR and percent diameter stenosis in patients with normal as well as increased LVMI. Interestingly, lesion length and LVMI were not found to have an independent effect on FFR measurement on multivariate analysis. The authors conclude that LVMI did not affect the relationship between percent diameter stenosis and FFR. The study has several limitations, as the authors point out. The first is the method of calculating LVM, which is not the most commonly used despite the fact that it was validated using autopsy and MRI studies. Of note, the mean percent diameter stenosis of the lesions examined was in the intermediate range of 61–62% in both groups. These lesions were matched based on angiographic findings which have significant limitations in cases of eccentric lesions or diffuse disesase. No physiologic testing was used as a comparison or reference to determine the hemodynamic significance of these lesions. This is important especially when evaluating a “new” application for FFR. Although noninvasive stress tests might have been logistically difficult to obtain on patients who underwent percutaneous interventions in the same setting, it could have been performed on patients in whom intervention was deferred. The third limitation is the lack of use of IVUS to better define plaque burden especially in cases of diffuse coronary disease where coronary angiography is significant limited. Overall, this is a good study which expands the application of FFR measurements to patients with increased LVMI. It demonstrates that FFR is a valid method for evaluating intermediate lesions in this patient population. This broadens the spectrum of utility of FFR for a physiologic-based revascularization approach in patients with intermediate epicardial coronary lesions seen on coronary angiography, and allows for the selection of patients who will benefit from revascularization vs patients in whom outcomes would be favorable even if intervention is deferred.⁹

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