Fractional Flow Reserve Gray Zone and Clinical Outcome

Study Questions:

What is the best treatment strategy for intermediate stenosis with fractional flow reserve (FFR) in the narrow “gray zone”?


From February 1997 to June 2013, all patients with single-segment disease and an FFR value within the gray zone or within the two neighboring FFR strata (0.70- 0.75 and 0.81-0.85) were included. Study endpoints consisted of major adverse cardiovascular events (MACE: death, myocardial infarction [MI], and any revascularization) up to 5 years.


Out of 17,380 FFR measurements, 1,459 patients were included. Of them, 449 were treated with revascularization (Rev), and 1,010 with medical therapy (MT). In the gray zone, the MACE rate was similar (37 [13.9%] vs. 21 [11.2%], respectively, p = 0.3) between MT and Rev, while a strong trend toward higher rate of death or MI (25 [9.4] vs. 9 [4.8], p = 0.06) and overall death (20 [7.5] vs. 6 [3.2], p = 0.059) was observed in the MT group. Among MT patients, a significant step-up increase in the MACE rate was observed across the three FFR strata, especially with proximal lesion location. In Rev patients, the MACE rate was not different across the three FFR strata.


The authors concluded that FFR in and around the “gray zone” bears a major prognostic value, especially in proximal lesions.


This study reports that patients with an isolated stenosis located in a proximal coronary segment and FFR within the gray zone of 0.76-0.80 demonstrate a clinical outcome that is suboptimal when deferred to medical therapy alone. These data confirm the value of the 0.80 FFR threshold, and favor a revascularization strategy of coronary stenoses with FFR ≤0.80. These findings also narrow the “gray zone” for clinical decision making: Stenoses with an FFR below 0.80 deserve revascularization, while stenoses with an FFR above 0.80 are better treated with medical therapy, even though this cutoff needs to take into account the morphological characteristics of the stenosis and the clinical context of the patient.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease

Keywords: Constriction, Pathologic, Coronary Artery Disease, Coronary Stenosis, Fractional Flow Reserve, Myocardial, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization

< Back to Listings