Structure (Epicardial Stenosis) and Function (Microvascular Dysfunction) That Influence Coronary Fractional Flow Reserve Estimation

Abstract

Background. The treatment of coronary stenosis is decided by performing high risk invasive surgery to generate the fractional flow reserve diagnostics index, a ratio of distal to proximal pressures in respect of coronary atherosclerotic plaques. Non-invasive methods are a need of the times that necessitate the use of mathematical models of coronary hemodynamic physiology. This study proposes an extensible mathematical description of the coronary vasculature that provides an estimate of coronary fractional flow reserve. Methods. By adapting an existing computational model of human coronary blood flow, the effects of large vessel stenosis and microvascular disease on fractional flow reserve were quantified. Several simulations generated flow and pressure information, which was used to compute fractional flow reserve under several conditions including focal stenosis, diffuse stenosis, and microvascular disease. Sensitivity analysis was used to uncover the influence of model parameters on fractional flow reserve. The model was simulated as coupled non-linear ordinary differential equations and numerically solved using our implicit higher order method. Results. Large vessel stenosis affected fractional flow reserve. The model predicts that the presence, rather than severity, of microvascular disease affects coronary flow deleteriously. Conclusions. The model provides a computationally inexpensive instrument for future in silico coronary blood flow investigations as well as clinical-imaging decision making. A combination of focal and diffuse stenosis appears to be essential to limit coronary flow. In addition to pressure measurements in the large epicardial vessels, diagnosis of microvascular disease is essential. The independence of the index with respect to heart rate suggests that computationally inexpensive steady state simulations may provide sufficient information to reliably compute the index.