Coronary Physiologic Assessment Based on Angiography and Intracoronary Imaging

QFR

With the advent of the QFR, a unique non-invasive approach has been established to evaluate the hemodynamic importance of coronary stenoses without the use of vasodilators. A 3D model of the target vessel is constructed based on two angiographic projections with a minimum separation of 25°.^[7] A quadratic function may be used to estimate contrast flow velocity acquired from frame-count analysis to determine an individual’s particular virtual hyperemic flow velocity. After segmenting the vessel, the program determines its QFR. Similar to FFR angio, QFR shortens the time, it takes to evaluate a patient’s physiological status by around 30% compared to traditional wire-based FFR.^[8]

QFR analysis

To evaluate QFR, specialized software (QAngio XA 3D version 1.2, Medis Medical Imaging Systems) is used [Figure 2]. When possible, it is preferable to utilize the angiographic projections recommended by the QFR software’s developer to ensure an accurate QFR computation. The contrast QFR is calculated when the vessel diameter is smaller than 2.0 mm by counting the frames between the index vessel’s ostium and a distal anatomic landmark that is discernible in both projections. Distal endpoints are selected at a minimum vessel diameter of 1.5 mm when the proximal reference diameter of the vessel is between 2.5 and 2.0 mm. The typical threshold is −0.80.^[9,10] The following are some exclusion criteria inappropriate for a QFR analysis: The lack of isocenter calibration, major artery overlap or foreshortening, severe vascularity, poor contrast, TIMI flow ≤2, tachycardia more than 100 beats/min, atrial or ventricular atrial fibrillation, ostial left main or ostial right coronary stenosis, 1,1,1 Medina-classified singularity lesions, and vessels with retrograde flow are some other factors.^[8-10]

Close

Figure 2:

Quantitative flow ratio (QFR) analysis (Courtesy of Xu et al.). An illustration of how angiography might have missed a revascularization signal in the left anterior descending artery, that was significant on QFR with value of 0.76. Here are some pictures showing the vessel’s diameter and QFR curves as measured along its length: (a and b) two angiographic projections separated by a 25° angle; (c) a 3D reconstruction of the vessel; and (d) vessel diameter, and QFR curves over the length of the vessel.

Export to PPT

In the Functional Assessment by Various Flow Reconstructions (FAVOR) Pilot study,^[8] the FAVOR (Functional Diagnostic Accuracy of QFR in Online Assessment of Coronary Stenosis) II China,^[9] and the FAVOR II Europe-Japan studies,^[10] the diagnostic performance of QFR was shown. Based on a recent meta-analysis that included 819 patients and 969 lesions along with the Wire-Free Functional Imaging II Study,^[11] QFR was found to have excellent diagnostic performance in identifying coronary stenosis with hemodynamic significance, as defined by FFR 0.80 (sensitivity 84%, specificity 88%, positive predictive value [PPV] 80%, negative predictive value [NPV] 95%, and area under the receiver operating characteristic curve (AUC] 0.92).^[12] A recent large-scale, multicenter, and observational registry with 599 vessels in 452 patients was used to assess QFR’s diagnosis accuracy across a broad range of clinical and patient subgroups. QFR has demonstrated excellent diagnostic accuracy in predicting the functional significance of coronary stenoses regardless of patient variables such as sex, diabetes mellitus, or lesions of the acute coronary syndrome. This method outperformed FFR angio for diagnosing lesions in the RCA and LCX (sensitivity 92%; specificity 91.6%; AUC 0.96). The predictive importance of QFR was also investigated in this observational study and it was shown that vessels with a QFR of 0.80 were more likely to have a vessel-oriented composite outcome. Using cardiac mortality, target-vessel myocardial infarction, and ischemia-driven target lesion revascularization, the researchers explained the outcome.^[13] QFR-guided technique to lesion selection yielded superior clinical outcomes at 1 year compared to standard angiography guidance in a study of 3825 patients undergoing percutaneous coronary intervention (PCI) in FAVOR III China.^[14]

Applications of QFR

Recent research shows incremental diagnostic and prognostic improvement over angiography alone in STEMI patients treated with QFR, even in non-culprit lesions. Due to its ability to predict future unfavorable events like spontaneous MI and revascularization related to NCLs without the need for additional measures beyond diagnostic angiography and specialized software, the safe and noninvasive QFR procedure may be of particular importance to streamlining the effective workflow for patients with STEMI.^[12]

caFFR

The caFFR index is a new technique for the physiological assessment of the severity of coronary artery stenosis based on angiographic images. Calculating the pressure drop from the coronary ostium to every location in the vessel and determining the caFFR value of each location in the vessel can be done using fluid mechanics, the TIMI frame counting technique, an optimized CFD program, and the two-dimensional analysis and three-dimensional reconstruction of two coronary angiography image series with an angle-off >30°. CaFFR is cutting edge because it uses a pressure transducer to monitor aortic pressure in real-time (FlashPressure, Rainmed Ltd.). Taking the mean aortic pressure across five heartbeats yields the hyperemic aortic pressure. Counting frames to build a baseline velocity allows one to automatically calculate the hyperemic flow velocity. In the end, a pressure decrease across the lesion is calculated using a unique pressure-flow dynamics computational approach (CPFD). The Accuracy of Computational Pressure-Fluid Dynamics Applied to Coronary Angiography to Derive FFR (FLASH FFR) study used a prospective and multicenter analysis of 328 lesions in 328 patients to evaluate the feasibility of the caFFR system and the diagnostic performance of the caFFR using invasive FFR as the gold standard. Consistently superior diagnostic performance was demonstrated by the data (sensitivity 90%, specificity 99%, PPV 97%, NPV 95%). R = 0.89 demonstrated a very strong connection. Getting a caFFR value took just 4.5 min to run, with the computation time being <1 min of that.^[20] Clinical outcomes and health-care expenditures were compared between the caFFR-guided approach and the FFR-guided strategy in the Flash FFR II study, a prospective, multicenter, randomized, and non-inferiority trial is currently ongoing.

Accurate measurement of angiography-based indices

High-quality image capture and precise reconstruction of the coronary artery’s morphology are crucial since the validity of angiography-based indices is heavily reliant on the caliber of the angiograms themselves. In particular, the target vessel should be scanned in a perfect field of view without shifting the table following intracoronary injection of nitroglycerine. When imaging particular lesion segments, it is best to do so from the appropriate projection angles to reduce the likelihood of overlap between side branches and foreshortening of the artery. Selecting the lumen boundary may take some manual tweaking, although better images may shorten the procedure time. When applying these cutting-edge techniques, it is crucial to take the lesion’s location into account in addition to its vessel characteristics. Such a method may not be appropriate for aorto-ostial stenoses, for instance, since an inserted guide catheter and contrast backflow might lead to erroneous 3D reconstruction. The previous studies often excluded patients with severe widespread disease, left main stenosis, or bifurcation lesions since it was advised that these patients be investigated differently.

Imaging-based FFR

Optical coherence tomography (OCT) and intravascular ultrasonography (IVUS) are imaging modalities that might guide and enhance PCI techniques. Functional assessments of coronary lesions are hampered by the fact that cross-sectional and two-dimensional data like minimal lumen area (MLA) have poor to moderate diagnostic accuracy for predicting FFR <0.8 in arteries other than the left main coronary artery.^[21,22] The same methods used to compute FFR from angiography have been tried so far to calculate FFR from IVUS or OCT images.

OCT-derived FFR (OFR)

OFR is a novel technique allowing the assessment of flow-limiting coronary stenosis without the use of a pressure wire or artificially induced hyperemia. More research has been done on OFR, making it the preferred method of determining FFR using OCT. A prototype software application can calculate the OFR and draw the lumen for an experienced analyst who is blinded to the FFR data (OctPlus; Pulse Medical Imaging Technology, Shanghai, China).

For each OCT image pullback, the lumen of the coronary artery is automatically delineated and the side branches are automatically detected. Subsequently, the cut-plane perpendicular to the side branch centerline is reconstructed and the area of the side branch ostium in the cut-plane is computed.^[29] Next, the step-down behavior across bifurcations is included into the calculation for the reference vessel size according to the principles of bifurcation fractals (the healthy lumen as if there were no stenosis).^[30] Assuming the flow is incompressible, the concept of mass conservation may be applied using the area-preservation model. The final step, which uses a unique methodology derived from an adapted and true computational FFR method, is to compute the OFR value at each place along the probed vessel using the intake boundary. Multiplying the area of the proximal reference lumen shown on OCT by a made-up hyperemic flow rate of 0.35 m/s yields the hyperemic volumetric flow rate. The computed OFR values are used to color code the rebuilt artery, with the value at the furthest location being compared to FFR [Figure 7]. The location of the cut plane and the lumen shape may be manually adjusted if necessary due to poor OCT picture quality or imaging artifacts.” The process may be automated in its entirety otherwise. With a high sensitivity (87%) and specificity (92%), as well as a quick analysis time (<1 min on average 29–31), OFR proved to be an effective diagnostic tool for predicting FFR ≤0.80.^[31]

Close

Figure 7:

An example of optical coherence tomography (OCT)-derived fractional flow reserve (FFR). (a) Coronary angiography revealed angiographically intermediate stenosis in the proximal part of the left anterior descending artery (arrowheads) with a wire-based FFR value of 0.77. (b) Images obtained from OCT using the FFR value in OctPlus software (Courtsey of Kleanthis Theodoropoulos et al.).

Export to PPT

Without the necessity for 3D vessel reconstruction, Seike et al. devised a unique approach for predicting OCT-based FFR using fundamental fluid dynamics. Their method for determining FFR exhibited a greater connection with wire-based FFR (r = 0.89) compared to MLA (r = 0.68) and % area stenosis estimated by OCT (r = −0.7032). However, more research is needed to confirm their findings, which show that FFR may be predicted from OCT data using a simple fluid dynamics equation. Abbott is now supporting the prospective and multicenter FUSION (functional diagnosis of coronary stenosis) study, which will compare the diagnostic performance of an OCT-derived FFR (Virtual Flow Reserve: VFR) to that of a wire-based FFR in roughly 310 patients.^[32]

Angiography-based indices future direction

Recent research has shown that wire-based FFR and angiographic FFR correlate well, and the latter provides a reasonably quick physiologic evaluation of coronary stenosis. An angiography-based FFR may become a standard tool in clinical practice for determining the indication for PCI if randomized and controlled trials show non-inferior or superior clinical outcomes compared to a pressure-wire guided strategy or an angiography-guided strategy (PCI). One-year results from the DEFINE-PCI (Physiologic Assessment of Coronary Stenosis Following PCI) study recently shown the positive correlation between an iFR of 0.95 following PCI and clinical outcomes.^[33] From a physiological perspective, it is crucial to enhance PCI, and focus is shifting in that direction. Mavromatis et al. claim that trans-stent FFR gradient (TSG) of >0.04 is similarly linked to poor long-term outcomes following PCI.^[34] After PCI, FFR based on angiography may be used to assess physiologically effective revascularization; however, the usefulness of this method after PCI has to be studied [Figure 8]. Since fewer stents would be inserted and the use of an expensive pressure wire will be eliminated, angiography-based FFR is anticipated to result in lower medical expenses. As a result, cost-benefit evaluations would still be necessary to demonstrate that a revascularization approach based on angiography-based FFR is cost-effective.

Close

Figure 8:

The future of coronary artery disease evaluation.

Export to PPT

The physiological assessment of coronary lesions is influenced by the pattern and distribution of coronary artery disease (CAD), including focal lesions, serial lesions, diffuse disease, and mixed patterns. Different CAD patterns have an impact on the accuracy of physiological indicators obtained from pressure wire and angiography, with diffuse disease in particular being a key sign of what to anticipate after PCI. The longitudinal functional assessment provides a third dimension to CAD characterization, in addition to the angiographic and functional evaluation of lesion significance.^[35]