Fractional flow reserve (FFR) is a technique to evaluate the haemodynamic relevance of coronary artery stenoses. It has become the gold standard method for assessing coronary lesion severity during invasive coronary angiography (ICA), translating to reduced coronary events and improved survival following percutaneous coronary intervention by identifying coronary lesions that cause myocardial ischaemia and selectively targeting these for intervention.
Invasive FFR 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 ICA. While such stenoses can be better verified during ICA, often the hemodynamic relevance of these stenoses cannot be evaluated from the ICA 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 ischaemia, 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 i.v. or i.a. injection of adenosine and the pressure gradient across the stenosis is measured. FFR is calculated as the ratio of the maximum blood flow distal to the stenosis divided by the maximum flow proximal to the stenosis. This trans-lesional 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 haemodynamic relevant stenoses 3.
Several prospective multicenter studies have demonstrated that FFR 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 FFR, especially since FFR also includes collateral blood flow distal to a stenosis. However, interventional FFR remains an invasive procedure with the inherent interventional risks.
Noninvasive computed FFR measurement
Recently, a new technique to allow for noninvasive calculation of FFR 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 hyperaemia 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 noninvasive FFR measurements1. In both studies, noninvasive measurements were compared with invasive FFR.
Both studies demonstrated that the diagnostic performance of computed noninvasive FFR 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 FFR is based on cCTA data, increased image noise, beam-hardening artefacts from metallic devices and especially motion artefacts can influence its quality. Since CT-based FFR research so far has only been performed with stable patients and nonacute 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 haemoglobin concentration.
- 1. Taylor CA, Fonte TA, Min JK. Computational fluid dynamics applied to cardiac computed tomography for noninvasive quantification of fractional flow reserve: scientific basis. J. Am. Coll. Cardiol. 2013;61 (22): 2233-41. doi:10.1016/j.jacc.2012.11.083 - Pubmed citation
- 2. Zarins CK, Taylor CA, Min JK. Computed fractional flow reserve (FFTCT) derived from coronary CT angiography. J Cardiovasc Transl Res. 2013;6 (5): 708-14. doi:10.1007/s12265-013-9498-4 - Free text at pubmed - Pubmed citation
- 3. Tesche C, De Cecco CN, Albrecht MH, Duguay TM, Bayer RR, Litwin SE, Steinberg DH, Schoepf UJ. Coronary CT Angiography-derived Fractional Flow Reserve. Radiology. 285 (1): 17-33. doi:10.1148/radiol.2017162641 - Pubmed