ABC | Volume 113, Nº2, August 2019

Viewpoint Update on Coronary Angiography-Based Physiology Technologies Alexandre Hideo-Kajita, 1, 2 Hector M. Garcia-Garcia, 1, 2 E van Shlofmitz, 2 C arlos M. Campos 3,4 MedStar Health Research Institute - Medstar Cardiovascular Research Network (MHRI/MCRN), Hyattsville, 1 Maryland – USA MedStar Washington Hospital Center, 2 Washington, District of Columbia – USA Universidade de São Paulo - Faculdade de Medicina Hospital das Clinicas Instituto do Coração, 3 São Paulo, SP – Brazil Hospital Israelita Albert Einstein - Cardiologia Intervencionista, 4 São Paulo, SP – Brazil Mailing Address: Carlos M. Campos • Av. Dr. Enéas de Carvalho Aguiar, 44 - Postal Code 05403-900 - São Paulo, SP – Brazil E-mail: carlos.campos@incor.usp.br Manuscript received August 01, 2018, revised manuscript November 08, 2018, accepted November 21, 2018 Keywords Coronary Artery Disease/physiopathology; Percutaneous Coronary Intervention; Angina, Stable; Coronary Angiography; Fractional Flow Reserve, Myocardial; Software/trends. DOI: 10.5935/abc.20190140 From the early stages of percutaneous coronary intervention (PCI), Andreas Grüentzig had advocated that the direct measurement of the trans-stenotic pressure gradient after balloon PCI should be used as a marker of successful PCI. 1 Since Grüentzig’s time, the physiologic assessment of coronary artery disease (CAD) has been tested and validated. 2 Currently, fractional flow reserve (FFR) is the standard of care for the online assessment of CAD physiology, identifying hemodynamically significant lesions in stable angina patients. 3,4 Albeit FFR is a relatively simple procedure, with a low complication rate, it comes with some intrinsic procedural risks and cost. Recently, non-hyperemic, resting index based physiology modalities have become an alternative to FFR but still require invasive assessment. Coronary angiography‑based physiology technology was developed to overcome the intracoronary wiring and additional medication administration that were necessary with invasive physiology. 5 Based on the principle of FFR, coronary angiography‑based physiology technology incorporates computational power by combining the 3-dimensional (3D) meshing (i.e. virtual reconstructions) of the coronary artery and the use of computational fluid dynamics (CFD) as a surrogate marker of the antegrade coronary artery blood flow. 6 Computational fluid dynamics The basis for CFD is derived from Navier-Stokes equations, a mathematical generalization of Euler’s flow of incompressible and frictionless fluids equation. 6 In its current state, CFD now can compensate for 3 dimensionality and interactions in the non-perfect cylindrical shape of the coronary arteries. 6 However, due to intrinsic cardiovascular physiology particularities, CFD cannot compensate for pulsatile blood flow effects; physiologic differences of coronary blood flow velocity in the proximal vs. distal segments of the vessel; and predictable loss of energy over a diseased vessel. 6-10 Moreover, CFD still cannot address the high complexity interactions in vessel geometry that may lead to a chaotic vortex or turbulence formation and more importantly, the trans-lesional pressure drop. 6,10 There are significant differences in the complex rheological properties of blood and normal blood flow along the coronary artery tree branches by itself that are not taken into account in these models. This includes the Newtonian versus Non‑Newtonian fluid properties of blood that depend on the vessel diameter, the presence of a bifurcation, and slow blood flow shear stress effects (e.g. the non-Newtonian fluid property in that context). 6 CFD simulation generalizes the differences of Newtonian and Non-Newtonian fluids properties by the assumption that large vessels can be approximated to a Newtonian fluid property with constant viscosity. 11,12 Therefore, these data provide a consistent explanation of why these methods were not standardized to evaluate severe stenosis or antegrade blood flow in small vessels. 11 Computational time: Online vs. offline assessment One of the major limitations for the clinical adoption of CFD in the online software is the computational time. The computation time required to estimate the antegrade blood flow in the 3D-mesh model using CFD considerably prolongs the procedure duration. 11 In order to reduce the computational time and provide an online assessment of the vessel, most software developers substituted the CFD with mathematical coefficients. 11,12 The impact of this substitution was studied by Collet et al. and demonstrated no significant difference between the results obtained using either method to estimate vessel blood flow. 13 Online coronary angiography-based physiology software The development of online coronary angiography-based physiology software solutions occurred in parallel with different initiatives. Most commonly, their software solutions were tested and validated against invasive FFR, including Quantitative Flow Ratio (QFR), Cardiovascular Angiographic Analysis Systems-Vessel Fractional Flow Reserve (CAAS‑vFFR) and Fractional Flow Reserve Derived From Coronary Angiography (FFR angio ). 11,12,14 Each software solution however used different metrics (i.e. pressure vs. TIMI frame count) and anatomic considerations (i.e. single vs. multi-vessel) to build the 3D-mesh and solve the CFD challenges of non‑invasively predicting invasive FFR measurements, making a fair comparison among them unlikely. 11,12,14 In its current state, the overall performance of online coronary angiography-based physiology was evaluated in a Bayesian meta-analysis showing a pooled sensitivity of 0.89, specificity of 0.90, the positive likelihood ratio of 282