Author + information
- Guglielmo Gallone, MD∗ (, )
- Luca Baldetti, MD,
- Alessandro Beneduce, MD and
- Francesco Giannini, MD
- ↵∗Interventional Cardiology Unit, Maria Cecilia Hospital, Via della Corriera 1, 48033 Cotignola (RA), Italy
In 1974, Gould and Lipscomb (1) demonstrated blunting of maximal hyperemic blood flow by narrowing the coronary artery diameter by 50%. With a bench-to-bedside translation, obstructive atherosclerotic lesions ≥50% were defined as hemodynamically relevant. The road was short from transmuting the concept of “hemodynamically significant coronary stenosis” to that of “ischemia-causing” stenosis. When these lesions were accordingly targeted to improve prognosis, disappointment resulted from the unexpected lack of benefit (2). This led us to question the correlation between the severity of anatomical obstruction and the resulting ischemia of coronary stenosis. The advent of fractional flow reserve (FFR) to functionally assess the hemodynamical relevance of a stenosis was thus greeted with enthusiasm. Before long, the concept of “hemodynamically significant” stenosis was transmuted into that of “ischemia-causing” stenosis. Despite current acceptance of an FFR-guided approach to revascularization, its impact on the occurrence of myocardial infarction and cardiovascular mortality remains uncertain (2).
In the ReASSESS (PRrospEctive Comparison of FFR Derived From Coronary CT Angiography With SPECT PerfuSion Imaging in Stable Coronary ArtEry DiSeaSe) study (3), 143 patients with stable angina and evidence of at least 1 coronary stenosis of 40% to 90% at computed tomography angiography (CTA) underwent sequential assessment of “ischemia” using CTA-derived FFR (FFRCT) and single-photon emission computed tomography (SPECT). An invasive coronary angiography (ICA)-derived FFR value ≤0.80 in at least 1 vessel was then used as the reference to classify patients as having significant ischemia.
The per-patient sensitivities for identifying ischemia of FFRCT compared with those of SPECT were 91% and 41%, respectively (p <0.001), and the per-patient specificities were 55% and 86%, respectively (p < 0.001). The authors concluded that, in this population, FFRCT and SPECT have similar overall levels of accuracy in identifying hemodynamically significant stenosis (and, thus, ischemia according to the given study definitions).
Sand et al. (3) should be commended for their well-conducted study, giving insight to future directions to translate diagnostic accuracy into better outcomes.
However, a reassessment of the definitions underlying the study design is important to understand the true significance and the relative translational outlooks of the study.
In the ReASSESS study, an ICA-derived FFR ≤0.80 is used as the reference for diagnosing “hemodynamically significant stenosis” and to subsequently define “patient-level ischemia.” This overlap regarding the meaning of an abnormal FFR and ischemia is common in prior studies, including randomized trials, which favored wide adoption of this concept with implications for clinical practice and research. However, although a correlation exists between the hemodynamic significance of stenosis and the ischemic status of the underlying myocardium (3), this is not a 2-variable equation, and an attempt to make it so oversimplifies the complex interplay of factors including, among others, the physiology of coronary microvasculature (4). This is not mere sophistication, as it has important implications which may go unnoticed in clinical practice. In this perspective, there are tests that evaluate the hemodynamics of a coronary segment and those that evaluate the myocardial perfusion of a coronary territory (e.g., myocardial perfusion imaging [MPI]). Indeed, FFR and coronary flow reserve (CFR, parametric imaging myocardial perfusion) are discordant in 30% to 40% of intermediate coronary stenoses (4), with an FFR ≤0.80 in the context of normal CFR having low risk, although impaired CFR and an FFR >0.80 confer increased cardiovascular risk (4). Further balancing is needed considering that MPI is based chiefly on a comparison of vasodilator-mediated relative increment of blood flow rather than on biological markers of myocyte ischemia.
How do these concepts apply to the ReASSESS study? In this study, 59% of the patients with FFR ≤0.80 had no signs of ischemia by SPECT imaging, other than being all “false-negative SPECT results” as suggested by the authors. Many of these patients may have hemodynamically significant stenoses that do not cause ischemia and do not therefore require revascularization (a hypothesis yet to be tested). In this perspective, noninvasive strategies assessing hemodynamic significance of a stenosis (i.e., FFRCT) should be seen as complementary rather than alternative to a strategy assessing MPI, whether it is nuclear perfusion imaging, stress cardiac magnetic resonance, or the emergent CT-MPI, which has the potential to be integrated with FFRCT. In the future, the noninvasive identification of patients without flow-limiting stenosis and ischemia or with flow-limiting stenosis not causing ischemia may directly trigger appropriate management, avoiding unneeded ICA assessments and possibly improve outcomes.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
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