Noninvasive fractional flow reserve derived from coronary computed tomography angiography for identification of ischemic lesions: a systematic review and meta-analysis

As the most common cause of cardiovascular disease mortality, the prevalence of coronary artery disease (CAD) is still increasing worldwide1. For diagnosis of CAD, invasive coronary angiography (ICA), the standard approach historically, is limited to provide only anatomic information2. Percutaneous coronary intervention (PCI) decision based merely on ICA can result in unbenefited stenting of functionally non-significant lesions or inappropriate deferral of PCI of functionally significant lesions3. Fractional flow reserve (FFR), measured during ICA, has been established as the reference standard in evaluating the functional significance of a coronary stenosis4. In addition, the clinical utility of FFR as a decisive tool for revascularization therapy has been evaluated by several prospective randomized trials, demonstrating how FFR-guided PCI can optimize benefits of revascularization and improve long-term outcomes compared with angiographic guidance alone5,6,7,8. Revascularization decision with FFR guidance has also been shown to be a sound strategy in terms of cost-benefits with significantly fewer stents implanted and less contrast agent used in comparison with PCI guided by ICA alone9. Nevertheless, FFR is an invasive method after all, bringing potential procedural risks for patients4. An alternative technique called noninvasive fractional flow reserve derived from coronary computed tomography angiography (FFRCT) has been developed10. Through utilization of computational fluid dynamics and coronary artery images acquired from coronary computed tomography angiography, FFRCT enables estimation of FFR value without the need for additional invasive imaging, modification of acquisition protocols, or extra administration of medication. Hence, it is able to provide information both on the anatomic severity of a coronary lesion and its functional significance in a relatively safe and economical manner. Since its feasibility was initially validated in 201111, a number of clinical studies have been conducted to evaluate the diagnostic efficacy of FFRCT using FFR as the reference standard12,13,14,15. Previous meta-analyses have evaluated the diagnostic performance of FFRCT both at the per-patient level and the per-vessel or per-lesion level as defined by the invasive FFR16,17. However, concerns have been raised about the applicability of univariate model in pooling estimates of sensitivity and specificity, either with fixed- or random-effects model, which might inadvertently produce inaccurate results by ignoring threshold effects and correlation between the two estimates18. Moreover, results of new diagnostic accuracy tests for assessment of FFRCT have recently been published as full papers19,20. Therefore, an updated meta-analysis was carried out to comprehensively search and review evidence available heretofore and derive reliable assessment of the diagnostic performances of FFRCT using a bivariate model as the method for pooling diagnostic measures.