**7. CT-FFR**

The invasive measurement of the fractional flow reserve is currently the accepted reference standard to determine, whether a coronary stenosis is hemodynamically relevant and is therefore implemented in the guidelines [70]. The FAME study has proved that FFR guided coronary revascularization is associated with reduced rates of death, myocardial infarction or target vessel revascularization [71]. In clinical routine, the use of invasive FFR is associated with risks and complications such a severe bleeding, arrhythmia, stroke, and coronary dissections depending on the experience of the interventional cardiologist [72].

CT myocardial perfusion imaging offers great potential to reclassify findings in cCTA and to evaluate the myocardial blood supply [68]. Regarding risk of invasive coronary angiography [69], an initial noninvasive diagnostic selection would be desirable to reduce invasive angiograms, showing no obstructive CAD. Addition of CTMP to cCTA holds highly promising potential to adopt this role and to establish CT as a single imaging examination for comprehensive evaluation of CAD and direct assessment of myocardial ischemia in one examination (**Figure 1**).

**Figure 1.** 59-year-old female with known hypertension presenting with chest pain. (I) cCTA show several moderate stenoses of the LAD (arrows). **(II)** DECT show minor iodine distribution within basal LAD and RCA territory as a sign of hemodynamic significance (arrows). **(III)** Invasive catheter angiography show severe artery disease of all three vessels. Subtotal stenosis of RCA, significant stenosis of the left main trunk (arrow) and 75% stenosis of mid RCX and Ramus marginalis. cCTA, coronary computed tomography; DECT, dual-energy computed tomography; LAD, left anterior

descending; RCA, right coronary artery; RCX, ramus circumflexus.

tomography angiography; LAD, left anterior descending.

The invasive measurement of the fractional flow reserve is currently the accepted reference standard to determine, whether a coronary stenosis is hemodynamically relevant and is

**Figure 2.(A)** cCTA shows stenotic noncalcified plaque of the LAD. **(B + C)** Color-coded automated plaque quantification by the analysis software showed the plaque composition as predominantly noncalcified. cCTA, coronary computed

**7. CT-FFR**

206 Interventional Cardiology

Novel technologies have been developed to calculate noninvasive FFR from routine cCTA datasets using computational fluid dynamics. The main advantage of this technology is the markly improvement of specificity and positive predictive value compared to standard cCTA, without additional stress medication, image protocols, and radiation exposure (**Table 5**). While the first studies concentrated on the general feasibility and diagnostic performance, further clinical studies validated the cost-effectiveness. The PLATFORM-study showed that the numbers of patients without anatomically obstructive CAD (*p* < 0.0001) could be significantly improved with the CT-FFR arm, while the secondary endpoint radiation exposure showed no difference (9.9 vs. 9.4 mSv, *p* = 0.20) [73].

There are the first head-to-head comparisons of CT-FFR compared stress CT myocardial perfusion (CTP) in patients with CAD with a per-vessel specificity of was 66% for cCTA, 77% for CT-FFR, and 91% for CTP, respectively, while the diagnostic performance of cCTA alone


CT-FFR <0.80 (95% CI) und cCTA stenosis ≥50% (95% CI) [in brackets] were defined as cut-off values. AUC, area under the curve; cCTA, coronary CT-angiography; CT-FFR, CT-based FFR; FFR, Fractional flow reserve; N.A., not available; NPV, negative predictive value; PPV, positive predictive value.

**Table 5.** Diagnostic accuracy of CT-FFR and cCTA compared to invasive FFR as the reference standard on a per vessel (n = 1306) basis.

was significantly improved by combination with CT-FFR or CTP [74]. Meta-analysis shows that CT-FFR can act in the context of other myocardial perfusion modalities as a potential gatekeeper for invasive revascularization (**Table 6**) in patients with suspected or known CAD using invasive FFR as the reference standard [75]. Due to time-consuming off-site calculation and transfer of the datasets to external core laboratory the clinical impact is limited. Thus, a novel solution for physician-driven CT-FFR derivation using regular on-site workstations was developed. This CT-FFR algorithm applies reduced-order models for more expeditious calculation, but is currently not commercially available [76].


Adapted from von Gonzalez et al. [82] and Takx et al. [75]. AUC, area under the curve; cCTA, coronary CT-angiography; CT-FFR, CT based fractional flow reserve; FFR, fractional flow reserve; N.A., not available; NLR, negative likelihood ratio; PLR, positive likelihood ratio.

**Table 6.** Diagnostic accuracy of CT-FFR and other non-invasive modalities compared to invasive FFR.

Currently, CT-FFR is an interesting and sophisticated approach to identify functionally significant CAD in a noninvasive way. However, this promising technique is still in development and searching for its clinical application, and further evidence studies are necessary before CT-FFR is implemented for clinical use.
