Relationship between pressure-based and flow-based fractional flow reserves in serial coronary stenoses: A numerical study validated by <i>in vitro</i> experiments

Multiple stenoses coexisting in a coronary artery (termed serial stenoses) are frequently observed in patients with coronary artery disease. Serial stenoses induce complex changes in coronary hemodynamics, particularly in blood flow rates and pressure drops across individual lesions, thus complicating the assessment of stenosis-specific functional impact. In this study, multiscale model-based numerical simulations were carried out, in combination with in vitro experiments and theoretical analysis, to systematically investigate pressure-based fractional flow reserve (PFFR), flow-based FFR (QFFR), and their relationship at serial stenoses located, respectively, in the proximal and middle portions of the left anterior descending artery. Numerical results revealed that PFFR and QFFR at the upstream stenosis exhibited different sensitivities to the downstream stenosis, leading to inconsistent diagnostic outcomes under certain conditions. In contrast, PFFR and QFFR at the downstream stenosis were equivalent in value and sensitive to both stenoses. The presence of a branch artery between the stenoses attenuated the influence of the downstream stenosis on PFFR and QFFR at the upstream stenosis. In vitro experiments validated the accuracy of the computational models and confirmed the numerical findings. Moreover, numerical data-based regression analyses revealed that QFFR at the upstream stenosis could be estimated using a function of PFFRs at the upstream and downstream stenoses, which was further verified by theoretical model-based analysis. These findings provide theoretical evidence for understanding stenosis-specific characteristics of functional indices in serial stenoses and offer a practical approach to optimize clinical diagnosis using PFFRs measured at multiple stenoses.