Author + information
- Gilles Rioufol, MD, PhD⁎ ( and )
- Gérard Finet, MD, PhD
- ↵⁎Reprint requests and correspondence:
Dr. Gilles Rioufol, Interventional Cardiology Department, Hospices Civils de Lyon, and INSERM 1060, CARMEN, Cardiovascular Hospital, 28 avenue Lépine 69677 Bron cedex, France
Beware so long as you live of judging men by their outward appearance., —Jean de la Fontaine (1)
Following Gould and Lipscomb's seminal work in the 1970s, 50% coronary stenosis was shown to be liable to reduce arterial blood flow in hyperemia: that is, in a situation pragmatically equivalent to maximal effort (2). At the time, functional flow analysis was not technologically feasible, and coronarography became the reference tool for diagnosis, prognosis, and stratification of coronary patients, despite the limitations of angiography (3). Subsequently, this 50% threshold became consecrated as indicating significant stenosis and possible revascularization strategy. Improved visualization of coronary atheroma was later provided by intravascular ultrasound (IVUS), enabling routine arterial analysis at a resolution higher than with angiography (roughly 100 μm vs. 250 μm), free of plane confusion, and with arterial wall visualization, which angiography cannot provide (4).
In the late 1990s, device miniaturization allowed the possibility of routine study of coronary hyperemia under pharmacological stimulation, and fractional flow reserve (FFR) proved its clinical interest in diagnosing functionally significant stenosis (5), presently defined by consensus by an FFR threshold of <0.80 under maximal hyperemia (6).
The temptation to correlate easily accessible IVUS data to the functional information provided by FFR, not yet widely available, led Takagi et al. (7) in 1999 to recommending a 3-mm2 IVUS minimum lumen area (MLA) cutoff as detecting stenosis with FFR <0.75 and with 83% sensitivity and 92% specificity. This 3-mm2 threshold has since been regularly adopted as a surrogate for functionally significant stenosis.
Given that the anatomic distribution of the coronary network displays a fractal geometry, it seemed curious that there should be 1 magic number for MLA. Moreover, the functional implications of epicardial coronary stenosis depend, not simply on the degree of stenosis in the epicardial conductance vessel, but also on stenosis length, myocardial microcirculation bed, the myocardial mass perfused by the artery, and the degree of collateral circulation (8): functional assessment focusing on degree of stenosis can only be reductive.
Since the 2000s, FFR-based functional strategies have proved more effective than oculostenotic angiographic strategies in single vessel (9) as in multivessel disease patients (6). The time had come to revise the relevance of anatomic stenosis analysis as surrogate for functional impact.
In this issue of JACC: Cardiovascular Interventions, Koo et al. (10) thus undertook a rigorous methodological comparison of FFR versus IVUS in 267 stenoses throughout the coronary arteries. Patient selection for stable coronary lesion with underlying myocardium free of ischemic history enabled robust conclusions to be drawn.
Their main conclusion was that there is no threshold for lumen area reliably associated with FFR <0.80.
Lesions were pragmatically classed as proximal, medial, or distal along the arteries and the correlations (except for the proximal left anterior descending coronary artery [LAD]) were very poor. A proximal LAD lesion will admittedly show a better receiver-operator characteristic curve in case of MLA <3 mm2, the same value as in Takagi et al. (7); however, 1 in 4 stenoses with MLA >3 mm2 will nevertheless show FFR <0.80, which is a lot of uncertainty as far as the individual patient is concerned.
A recent study by another Korean team (11), with a comparable number of patients and an almost identical design, came to the same conclusion: >2.4 mm2 MLA stenosis rules out FFR <0.80 in 96% of cases, but <2.4 mm2 MLA is associated with <0.80 FFR in only 37%. Nondissociation between different arterial segments probably accounts for these findings.
The second major finding by Koo et al. (10) was the importance of the LAD. An intermediate lesion (30% to 70% angiographic stenosis) was 3.4 times as likely to be functionally significant if it was located on the LAD rather than on any other artery, and this probability was further increased (odds ratio [OR]: 2.97) if the lesion was, moreover, proximal. These findings were borne out by Kang et al. (11), who reported comparable ORs for the LAD (OR: 4.4), although without difference according to proximal stenosis location.
These findings may have practical routine consequences. It would certainly henceforth be advisable, in case of positive stress test and only moderate proximal LAD atheroma on angiography, to supplement invasive exploration with FFR before concluding in favor of a false-positive stress test: a false negative on the angiogram would be more likely.
Conversely, an angiographically tight lesion on the distal LAD is unlikely to be associated with inducible ischemia, and systematic revascularization needs reconsidering.
Finally, does IVUS still have any role to play in stable angina? As far as diagnosis is concerned, that is a good question; in the actual performance of complex angioplasty, on the other hand, there remains no doubt that IVUS is of great help and can optimize prognosis (12). Left main (LM) lesions were not studied by Koo et al. (10), but this particular anatomic situation deserves special attention: the proximal location limits the variability of anatomic measurement, and although FFR has been validated for diagnosis and prognosis (13), MLA <5.9 mm2 on IVUS was validated against FFR (14) as indicating significant LM lesion and guiding strategy. In LM evaluation, IVUS, unlike FFR, provides useful information on plaque morphology and extension to LAD and circumflex ostia, lengths, and reference diameters. Such anatomic data may guide a strategy of interventional revascularization and optimize results (15), whereas FFR provides no such anatomic information. A role thus remains for IVUS in the diagnosis and interventional treatment of LCA stenosis in centers where the policy is PCI; when, however, PCI is not intended, FFR is pragmatically the method of choice.
In conclusion, in light of the findings by Koo et al. (10) and other teams, the debate between morphological and functional approaches is going ever more in favor of function, and so of FFR, in evaluating coronary stenosis. If IVUS has lost its place in the evaluation of stable ischemia despite its good resolution, then logically, the same should go for angiography and for cross-sectional imaging such as computed tomography scan and optical coherence tomography. In Europe, FFR currently enjoys class IA recommendation for assessment of stable coronary stenosis ahead of revascularization (16) when functional information is lacking; the question of generalizing FFR as a first-line cath lab tool is henceforth on the table.
Both authors have reported that they have no relationships to disclose.
↵⁎ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
- American College of Cardiology Foundation
- ↵J. Fables de la Fontaine. Book VI. 1668: Fable 5.
- Topol E.J.,
- Nissen S.E.
- Mintz G.S.,
- Nissen S.E.,
- Anderson W.D.,
- et al.
- Takagi A.,
- Tsurumi Y.,
- Ishii Y.,
- et al.
- Kern M.J.,
- Samady H.
- Pijls N.H.,
- van Schaardenburgh P.,
- Manoharan G.,
- et al.
- Kang S.J.,
- Lee J.Y.,
- Ahn J.M.,
- et al.
- Roy P.,
- Steinberg D.H.,
- Sushinsky S.J.,
- et al.
- Hamilos M.,
- Muller O.,
- Cuisset T.,
- et al.
- Jasti V.,
- Ivan E.,
- Yalamanchili V.,
- Wongpraparut N.,
- Leesar M.A.
- Park S.J.,
- Kim Y.H.,
- Park D.W.,
- et al.,
- MAIN-COMPARE Investigators
- Wijns W.,
- Kolh P.,
- Danchin N.,
- et al.