Quantitative Flow Ratio-Guided Revascularization

Corresponding Author

The discrepancy in severity between visual and functional evaluation of a stenosis has long been recognized as one of the fundamental limitations of coronary angiography. Lesion-specific factors such as location, length, eccentricity, and shape are all subtleties that influence visual-functional mismatch and cannot be easily discerned with an “eyeball” of the 2-dimensional angiogram,¹ which remains the modus operandi for assessing stenosis severity in most catheterization laboratories around the world.

Fractional flow reserve (FFR) is the ratio of maximal myocardial blood flow in the presence of an epicardial stenosis to maximal myocardial blood flow in a disease-free vessel, reflecting the fraction of normal myocardial flow subtended by the interrogated vessel.² It is obtained by advancing a guidewire outfitted with a pressure sensor distal to a coronary lesion to measure distal coronary and aortic pressure under maximal hyperemia, a period when perfusion pressure becomes proportional to flow due to constant and minimal microvascular resistance.³ FFR is highly sensitive and specific at detecting myocardial ischemia,⁴ and randomized controlled studies have shown FFR to be superior to angiography in guiding percutaneous coronary intervention (PCI).5, 6, 7 A possible explanation for the improved outcomes with FFR guidance is its ability to identify high-risk lesions that exhibit pathological wall shear stress patterns independent of stenosis severity.⁸ However, despite the unequivocal benefits of FFR-guided PCI, its use remains limited in the real world.^9,10 Commonly cited barriers include costs, increased procedure time, patient discomfort secondary to pharmacological induction of hyperemia, and importantly, the potential risk of coronary dissection, which has been estimated to occur at a rate of 0.3% to 0.5%.¹¹

Quantitative flow ratio (QFR) is an angiography-based estimation of FFR that circumvents many of these obstacles by obviating the need for insertion of an intracoronary guidewire and induction of pharmacological hyperemia. QFR is computed by applying the principles of computational fluid dynamics in 3-dimensional quantitative coronary angiography–based reconstructions.¹² Studies of QFR have demonstrated good correlation and agreement with FFR, as well as good diagnostic accuracy for identifying myocardial ischemia when compared with FFR as the gold standard.12, 13, 14 In the FAVOR III China (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) study, patients randomized to QFR-guided PCI had significantly better outcomes compared with the angiography-guided PCI group, driven by lower rates of myocardial infarction (MI) and revascularization.¹⁵ These results compare favorably with those seen in the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study,⁶ and reinforces the notion that physiology-guided PCI results in superior outcomes compared with angiography-guided PCI, irrespective of the method used.

In this issue of JACC: Asia, Chen et al¹⁶ publish a prespecified subgroup analysis of the FAVOR III China study, focusing on sex-specific differences in outcomes between QFR- and angiography-guided PCI. The study cohort consisted of 2,652 men and 1,107 women, with the primary endpoint being a composite of all-cause death, MI, or ischemia-driven revascularization at 2 years. QFR-guided PCI led to a significant reduction in the primary endpoint compared with angiography-guided PCI in both males (8.7% vs 12.4%; HR: 0.69; 95% CI: 0.54-0.87) and females (8.0% vs 12.7%; HR: 0.62, 95% CI: 0.42-0.90), with no interaction between the sexes (P = 0.61). The benefits of QFR-guided PCI persisted in both sexes even after exclusion of periprocedural MI. Interestingly, a significant interaction between treatment effect and sex was found for the secondary endpoint of spontaneous MI, which occurred less often in females undergoing QFR-guided PCI (HR: 0.14 vs 0.58; P for interaction = 0.04).

The authors should be commended for providing detailed sex-specific analyses for an emerging technique in the field of coronary physiology, as there are known distinctions between the sexes with respect to FFR. A previous subgroup analysis of the FAME study found that FFR values were consistently higher in females compared with males that had similar angiographic stenosis severity, and that the proportion of functionally significant stenoses (FFR ≤0.80) was significant lower in females with intermediate lesions compared with males.¹⁷ There are 2 potential explanations for this sex-specific phenomenon. First, females undergoing PCI are usually older and more likely to have comorbidities such as hypertension and diabetes, leading to a higher prevalence of concomitant microvascular dysfunction. The presence of microvascular dysfunction limits the degree of hyperemic flow and results in a higher FFR compared with patients that have normal microvascular function and similar stenosis severity. Second, females are more likely to have smaller myocardial mass and myocardial perfusion territory, which leads to lower absolute coronary flow. Under these circumstances, a comparatively more severe stenosis is necessary to induce myocardial ischemia.

In contrast to FFR, QFR is heavily influenced by vessel geometry and utilizes frame count at rest to estimate hyperemic flow, which reduces the role the coronary microcirculation plays in its measurement.¹² Accordingly, there were no significant differences in QFR values between males and females with similar stenosis severity in this study.¹⁶ Although QFR guidance may have theoretically resulted in more females undergoing PCI than if FFR were performed, the consistent benefits seen in both sexes and lack of interaction should reassure clinicians that QFR-guided PCI remains valid and superior to angiography-guided PCI regardless of sex. The results from this study adds to the evidence supporting the use of QFR to guide revascularization. With continual improvement in image acquisition, ease of use, and integration of QFR into the standard catheterization laboratory workflow, we foresee a future in which physiology-guided PCI becomes the norm, rather than the exception, in clinical practice.

Funding Support and Author Disclosures

Dr Wong has reported that he has no relationships relevant to the contents of this paper to disclose. Dr Yong has received minor honoraria and research support from Abbot Vascular and Philips Healthcare.