Fractional flow reserve

Last revised by Hasan Emin Kaya on 4 Jan 2021

Fractional flow reserve (FFR) is a technique to evaluate the hemodynamic relevance of coronary artery stenoses 1,2. It is defined as "the ratio of maximal flow achievable in the stenotic coronary artery to the maximal flow achievable in the same coronary artery if it was normal" 1.

Fractional flow reserve has become the gold standard method for assessing coronary lesion severity during invasive coronary angiography (ICA). It enables the identification of specific coronary lesions that cause myocardial ischemia and can be targeted for revascularization. This translates to reduced coronary events and improved survival following percutaneous coronary intervention.  

Invasive fractional flow reserve measurement

Although coronary CT angiography has developed into a reliable non-invasive tool for the detection of coronary artery stenoses, further assessment and potential treatment still require invasive coronary angiography. While such stenoses can be better verified during invasive coronary angiography, often the hemodynamic relevance of these stenoses cannot be evaluated from the invasive coronary angiography imaging alone. While single-photon emission computed tomography has played a major role in evaluating myocardial perfusion deficiencies and thus evaluation of coronary artery disease, guidewire-based measurement of coronary blood pressure, flow-velocity and resistance now provide new diagnostic possibilities. In the coronary circulation, seminal work facilitated by coronary guidewire sensor technology now mean that interventional cardiologists can measure lesion-level ischemia, coronary collateral supply and other parameters of vessel function

During coronary catheterization a pressure wire is placed across the stenosis. To induce maximal flow in the coronary vessel, hyperemia is introduced as an intravenous/intra-arterial injection of adenosine and the pressure gradient across the stenosis is measured. Fractional flow reserve is calculated as the ratio of the maximum blood flow distal to the stenosis divided by the maximum flow proximal to the stenosis. This translesional pressure ratio during maximum flow expresses the 'functional significance' of a coronary lesion. Several studies have indicated that a FFR <0.8 is a reliable cut-off for hemodynamic-relevant stenoses 4,5.

Several prospective multicenter studies have demonstrated that fractional flow reserve during ICA with interventional revascularization improves the event-free survival rate and also leads to cost reduction of the procedures as only a fraction of detected coronary stenoses show a relevant obstruction of blood flow as determined by fractional flow reserve, especially since FFR also includes collateral blood flow distal to a stenosis. However, interventional fractional flow reserve remains an invasive procedure with the inherent interventional risks.

Non-invasive computed FFR measurement

Recently, a new technique to allow for non-invasive calculation of fractional flow reserve based on conventional coronary CT angiography (cCTA) data has been demonstrated. Computation is based on a development of an anatomic model of the epicardial coronary arteries for each case and calculating the maximum coronary flow during maximal hyperemia based on a mathematical model incorporating fluid dynamics. These post-processing steps require quantification of the patient-specific myocardial mass as this allows for an estimation of the baseline coronary blood flow.

Clinical evaluation of computed FFR measurements

Two large prospective multicenter studies, the DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve)  and the DeFACTO (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography) evaluated the diagnostic accuracy of CT-based non-invasive fractional flow reserve measurements 2. In both studies, non-invasive measurements were compared with invasive fractional flow reserve.

Both studies demonstrated that the diagnostic performance of computed non-invasive fractional flow reserve was superior for the detection of hemodynamically-relevant coronary stenoses compared to coronary CT angiography alone (DISCOVER-FLOW: accuracy of 84% vs 59%), mainly due to a reduction of false-positive findings detected by coronary CT angiography.


Since non-invasive determination of fractional flow reserve is based on cCTA data, increased image noise, beam-hardening artifacts from metallic devices and especially motion artefacts can influence its quality. Since CT-based fractional flow reserve research so far has only been performed with stable patients and non-acute cases, its accuracy in patients with acute coronary syndrome remains unknown. Furthermore, the post-processing steps may be time-consuming and costly. Finally, the model used for fluid dynamics may be inaccurate for patients with changes in the hematocrit or hemoglobin concentration.

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