Reply to “Letter to the editor: ‘A novel angiographic fractional flow reserve’”

Abstract

REPLY: We thank Dr. Yang and colleagues (7a) for their interest in our angiographic fractional flow reserve (FFR) study. This FFR technique, based on first-pass distribution analysis, was validated in a swine animal model. We share their enthusiasm for this angiographic technique that enables direct measurement of coronary flow and FFR for the determination of lesion-specific ischemia.In this study, FFR measurements were made at various stages of severity of microvascular disruption in the left anterior descending artery. Also, an external vascular occluder was used to produce a moderate epicardial stenosis. Therefore, the angiographic FFR technique was validated not only in the microvascular disruption model but also in the epicardial stenosis model (14). However, continued injections of microspheres may cause heterogeneous microinfarcts, which are not the same pathological change as normal myocardial infarction or diffused microvascular disease. The microspheres are not chemoattractant and thus are different from human microvascular disease (1). In human microcircular disease, dysfunction is usually caused by physical obstruction and active thrombogenic, vasoconstrictive, and inflammatory effects and their interactions with the vascular wall. Furthermore, other disease conditions, such as ventricular hypertrophy, diabetes mellitus, flow limiting diffuse coronary artery disease, and previous myocardial infarction, should be considered. The impact of other disease conditions on angiographic FFR requires additional studies.Angiographic FFR is calculated based on angiographic flow measurement. It was validated with direct flow measurements using flow probes, which is the gold standard. Previous studies have also correlated angiographic FFR with pressure-wire derived FFR (4,11,12), which is currently being used for clinical application. The results indicated that the FFR measured from pressure ratios overestimated the measurements using gold standard flow-probe FFR, especially at low FFR values (8). These results were in agreement with a previous report that compared coronary FFR, as defined by flow ratio, to myocardial FFR, calculated by a pressure ratio (10). Pijls et al. (6, 7) compared (P d Ϫ P v )/(P a Ϫ P v ) with the coronary flow ratio, where P d , P v , and P a are coronary distal, coronary venous, and aortic pressures, respectively. Their results showed that with increasing stenosis severity, the coronary flow ratio progressively underestimated the pressure-based index. Siebes et al. (8) and Spaan et al. (9) have demonstrated the curved nature of pressure-flow relation and how this shape relates to the pressure dependence of minimal coronary microvascular resistance (5). As expected, the flow-based FFR and pressure-derived FFR correlated well at the linear range of pressure and flow. The clinical trials that established the guidelines for FFR are based on pressure measurements. Therefore, it will be necessary to perform clinical trials to establish the guidelines of FFR based on angiographic flow measur...