ABC | Volume 113, Nº2, August 2019

Viewpoint Kajita et al. Coronary angiography-based physiology technologies Arq Bras Cardiol. 2019; 113(2):282-285 9.3, the negative likelihood ratio of 0.13 and the summary area under the receiver-operating curve of 0.84 compared to invasive FFR. 13 The individual characteristics of online coronary angiography-based physiology software solutions will be described below. Quantitative flow ratio (QFR) QFR (QAngioXA-3D prototype, Medis Medical Imaging System, Leiden, the Netherlands) is an angiography-based physiology software that uses the TIMI frame count of a single-vessel in two orthogonal views as the surrogate marker of blood flow to calculate the trans-lesional gradient ratio (Figure 1 A to D). In the latest reports, Favor II China trial, Xu B et al. 11 showed a linear correlation (r) between invasive FFR and QFR (online assessment) of 0.86 (p < 0.001) with a mean agreement difference of -0.01±0.06 (p = 0.006). 11 Spitaleri et al. 15 reported that the absence of revascularization of non-culprit lesions in ST-elevation segment myocardial infarction (STEMI) patients with QFR ≤ 0.80 increased the risk of clinical events in this population (HR 2.3; CI 95%, 1.2–4.5; p = 0.01). 15 Mejía-Rentería et al. 16 highlighted that coronary microcirculatory dysfunction (CMD) affects the overall diagnostic performance of QFR. 16 The QFR system has CE Mark and ANVISA clearance for clinical use. Clinical guidelines have not yet established the appropriate role of QFR in routine practice. Ongoing clinical trials including FAVOR III China (NCT03656848) may ultimately impact future guidelines. Cardiovascular angiographic analysis systems for vessel fractional flow reserve (CAAS-vFFR) CAAS-vFFR, PieMedical Imaging,Maastricht, TheNetherlands is single-vessel, two orthogonal view angiography‑based physiology software (Figure 1 E to H). The CAAS-vFFR validation study included 100 patients with intermediate lesions and stable CAD or non-STEMI. The CAAS‑vFFR and FFR mean value were 0.84 ± 0.07 and 0.82 ± 0.08, respectively. 14 The linear correlation of CAAS‑vFFR vs. FFR was 0.89 (p < 0.001) and CASS-vFFR showed a high inter-observer correlation of 0.95 (p < 0.001). In addition, CAAS-vFFR diagnostic accuracy for lesions with FFR ≤ 0.80 was 0.93 (p < 0.001). 14 CAAS-vFFR was the first angiography-based physiology system to receive Food and Drug Administration (FDA) “USA 510(k) approval” market clearance. Fractional flow reserve derived from coronary angiography (FFR angio ) Unlike QFR and CAAS-vFFR, the Fractional Flow Reserve Derived FromCoronary Angiography (FFR angio , CathWorks Ltd., Kfar-Saba, Israel) reconstructs the entire coronary artery tree using 3 single-plane angiographic projections (at least) and the mean aortic pressure to calculate a virtual FFR mapping of the 3D-model. 12,17 Fearon et al. 17 performed a global, multi-center validation study of FFR angio enrolling 301 all-comer patients (319 lesions). 17 FFR angio and invasive FFR measurements varied from 0.74-0.90 (median 0.83) and 0.5‑0.97 (median 0.85), respectively. The coefficient of correlation between FFR angio and invasive FFR was 0.80 (p < 0.001) and Bland‑Altman’s confidence limits were between -0.14 and 0.12 (95%). For lesions with invasive FFR ≤ 0.80, FFR angio (per vessel) demonstrated the sensitivity of 0.94, the specificity of 0.91 and area under the curve of 0.94. The overall FFR angio diagnostic accuracy was 0.92 and 0.87 for invasive FFR values between 0.75-0.85. 17 Finally, the inter-observer consistency of agreement between the methods was 0.96 (p < 0.001). 12 Physiology assessment cost-effectiveness A recurrent criticism of the routine use of invasive physiologic assessment (i.e. FFR) of CAD in the cardiac catheterization laboratory is the additional procedural cost. 18,19 For the non-invasive angiography-based physiology methods, cost-effectiveness data needs to be further investigated. This technology involves upfront institutional hardware and software costs, rather than a specific case-by-case cost of an invasive wire. Impact of physiologic lesion assessment on clinical outcomes Currently, with contemporary stents, target lesion failure (TLF, a composite of cardiac death, target vessel MI, or ischemia-driven target lesion revascularization - TLR) rates are similar (i.e. 4.0% to 6.0% at 12 months) to the rate of combined endpoint in the group of patients in whom PCI was deferred on the basis of FFR (i.e. overall unplanned revascularization of 5.0% at 12 months). 20 Thus, the rate of composite events for the treatment or deferral of PCI are similar, perhaps limiting the appropriate utilization of FFR for informing PCI decisions. 20-22 This needs to be further investigated in a contemporary clinical trial using 2 nd generation drug-eluting stents (2G-DES). Conclusion The majority of angiography-based physiology software solutions are currently available for research only. Clinical trials demonstrating clinical feasibility and reproducibility with a significant impact on clinical outcomes are needed. However, real-world studies are also needed to evaluate the reliability, integration and cost-effectiveness of these technologies in a clinical catheterization laboratory, since the prevalence of ischemic lesions in most studies is limited (i.e. 17% to 43%). 17 The angiography-based physiology technologies have great potential, but still need to be observed with a word of caution and the impact of these technologies remains unknown. Author contributions Conception and design of the research, Analysis and interpretation of the data, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Hideo-Kajita A, Garcia-Garcia HM, Shlofmitz E, Campos CM. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. 283