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Kahn, Andrew M.

Publications and source records attributed to Kahn, Andrew M..

Evaluation of intracoronary hemodynamics identifies perturbations in vorticity

Coronary artery disease (CAD) is highly prevalent and associated with adverse events. Challenges have emerged in the treatment of intermediate coronary artery stenoses. These lesions are often interrogated with fractional flow reserve (FFR) testing to determine if a stenosis is likely to be causative for ischemia in a cardiac territory. This invasive test requires insertion of a pressure wire into a coronary vessel. Recently computational fluid dynamics (CFD) has been used to noninvasively assess fractional flow reserve in vessels reconstructed from medical imaging data. However, many of these simulations are unable to provide additional information about intravascular hemodynamics, including velocity, endothelial shear stress (ESS), and vorticity. We hypothesized that vorticity, which has demonstrated utility in the assessment of ventricular and aortic diseases, would also be an important hemodynamic factor in CAD. Three-dimensional (3D), patient-specific coronary artery geometries that included all vessels >1 mm in diameter were created from angiography data obtained from 10 patients who underwent diagnostic angiography and FFR testing (n = 9). A massively parallel CFD solver (HARVEY) was used to calculate coronary hemodynamic parameters including pressure, velocity, ESS, and vorticity. These simulations were validated by comparing velocity flow fields from simulation to both velocities derived from in vitro particle image velocimetry and to invasively acquired pressure wire-based data from clinical testing. There was strong agreement between findings from CFD simulations and particle image velocimetry experimental testing (p < 0.01). CFD-FFR was also highly correlated with invasively measured FFR (ρ = 0.77, p = 0.01) with an average error of 5.9 ± 0.1%. CFD-FFR also had a strong inverse correlation with the vorticity (ρ = -0.86, p = 0.001). Simulations to determine the effect of the coronary stenosis on intravascular hemodynamics demonstrated significant differences in velocity and vorticity (both p < 0.05). Further evaluation of an angiographically normal appearing non-FFR coronary vessel in patients with CAD also demonstrated differences in vorticity when compared with FFR vessels (p < 0.05). The use of highly accurate 3D CFD-derived intravascular hemodynamics provides additional information beyond pressure measurements that can be used to calculate FFR. Vorticity is one parameter that is modified by a coronary stenosis and appears to be abnormal in angiographically normal vessels in patients with CAD, highlighting a possible use-case in preventative screening for early coronary disease.

59 BASIC BIOLOGICAL SCIENCES↗

Non-invasive characterization of complex coronary lesions

Conventional invasive diagnostic imaging techniques do not adequately resolve complex Type B and C coronary lesions, which present unique challenges, require personalized treatment and result in worsened patient outcomes. These lesions are often excluded from large-scale non-invasive clinical trials and there does not exist a validated approach to characterize hemodynamic quantities and guide percutaneous intervention for such lesions. This work identifies key biomarkers that differentiate complex Type B and C lesions from simple Type A lesions by introducing and validating a coronary angiography-based computational fluid dynamic (CFD-CA) framework for intracoronary assessment in complex lesions at ultrahigh resolution. Among 14 patients selected in this study, 7 patients with Type B and C lesions were included in the complex lesion group including ostial, bifurcation, serial lesions and lesion where flow was supplied by collateral bed. Simple lesion group included 7 patients with lesions that were discrete, <10mm long and readily accessible. Intracoronary assessment was performed using CFD-CA framework and validated by comparing to clinically measured pressure-based index, such as FFR. Local pressure, endothelial shear stress (ESS) and velocity profiles were derived for all patients. We validates the accuracy of our CFD-CA framework and report excellent agreement with invasive measurements (n=14,R 2 =0.6,p=0.0013). Ultra-high resolution achieved by the model enable physiological assessment in complex lesions and quantify hemodynamic metrics in all vessels up to 1mm in diameter. Importantly, we demonstrate that in contrast to traditional pressure-based metrics, there is a significant difference in the intracoronary hemodynamic forces, such as ESS, in complex lesions compared to simple lesions at both resting and hyperemic physiological states [n = 14, p=0.03]. Higher ESS was observed in the complex lesion group (7.0±4.7 Pa) than in simple lesion group (4.8±3.6 Pa). Complex coronary lesions have higher ESS compared to simple lesions, such differential hemodynamic evaluation can provide much the needed insight into the increase in adverse outcomes for such patients and has incremental prognostic value over traditional pressure-based indices, such as FFR.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Multilevel and multifidelity uncertainty quantification for cardiovascular hemodynamics

Standard approaches for uncertainty quantification in cardiovascular modeling pose challenges due to the large number of uncertain inputs and the significant computational cost of realistic three-dimensional simulations. Here, we propose an efficient uncertainty quantification framework utilizing a multilevel multifidelity Monte Carlo (MLMF) estimator to improve the accuracy of hemodynamic quantities of interest while maintaining reasonable computational cost. This is achieved by leveraging three cardiovascular model fidelities, each with varying spatial resolution to rigorously quantify the variability in hemodynamic outputs. We employ two low-fidelity models (zero- and one-dimensional) to construct several different estimators. Our goal is to investigate and compare the efficiency of estimators built from combinations of these two low-fidelity model alternatives and our high-fidelity three-dimensional models. We demonstrate this framework on healthy and diseased models of aortic and coronary anatomy, including uncertainties in material property and boundary condition parameters. Our goal is to demonstrate that for this application it is possible to accelerate the convergence of the estimators by utilizing a MLMF paradigm. Therefore, we compare our approach to single fidelity Monte Carlo estimators and to a multilevel Monte Carlo approach based only on three-dimensional simulations, but leveraging multiple spatial resolutions. We demonstrate significant, on the order of 10 to 100 times, reduction in total computational cost with the MLMF estimators. We also examine the differing properties of the MLMF estimators in healthy versus diseased models, as well as global versus local quantities of interest. As expected, global quantities such as outlet pressure and flow show larger reductions than local quantities, such as those relating to wall shear stress, as the latter rely more heavily on the highest fidelity model evaluations. Similarly, healthy models show larger reductions than diseased models. In all cases, our workflow coupling Dakota’s MLMF estimators with the SimVascular cardiovascular modeling framework makes uncertainty quantification feasible for constrained computational budgets.

59 BASIC BIOLOGICAL SCIENCES↗