Design and execution of a verification, validation, and uncertainty quantification plan for a numerical model of left ventricular flow after LVAD implantation

Abstract

Background Left ventricular assist devices (LVADs) are implantable pumps that act as a life support therapy for patients with severe heart failure. Despite improving the survival rate, LVAD therapy can carry major complications. Particularly, the flow distortion introduced by the LVAD in the left ventricle (LV) may induce thrombus formation. While previous works have used numerical models to study the impact of multiple variables in the intra-LV stagnation regions, a comprehensive validation analysis has never been executed. The main goal of this work is to present a model of the LV-LVAD system and to design and follow a verification, validation and uncertainty quantification (VVUQ) plan based on the ASME V&V40 and V&V20 standards to ensure credible predictions. Methods The experiment used to validate the simulation is the SDSU cardiac simulator, a bench mock-up of the cardiovascular system that allows mimicking multiple operation conditions for the heart-LVAD system. The numerical model is based on Alya, the BSC’s in-house platform for numerical modelling. Alya solves the Navier-Stokes equation with an Arbitrary Lagrangian-Eulerian (ALE) formulation in a deformable ventricle and includes pressure-driven valves, a 0D Windkessel model for the arterial output and a LVAD boundary condition modeled through a dynamic pressure-flow performance curve. The designed VVUQ plan involves: (a) a risk analysis and the associated credibility goals; (b) a verification stage to ensure correctness in the numerical solution procedure; (c) a sensitivity analysis to quantify the impact of the inputs on the four quantities of interest (QoIs) (average aortic root flow Q A o a v g, maximum aortic root flow Q A o m a x, average LVAD flow Q V A D a v g, and maximum LVAD flow Q V A D m a x); (d) an uncertainty quantification using six validation experiments that include extreme operating conditions. Results Numerical code verification tests ensured correctness of the solution procedure and numerical calculation verification showed a grid convergence index (GCI)95% <3.3%. The total Sobol indices obtained during the sensitivity analysis demonstrated that the ejection fraction, the heart rate, and the pump performance curve coefficients are the most impactful inputs for the analysed QoIs. The Minkowski norm is used as validation metric for the uncertainty quantification. It shows that the midpoint cases have more accurate results when compared to the extreme cases. The total computational cost of the simulations was above 100 [core-years] executed in around three weeks time span in Marenostrum IV supercomputer. Conclusions This work details a novel numerical model for the LV-LVAD system, that is supported by the design and execution of a VVUQ plan created following recognised international standards. We present a methodology demonstrating that stringent VVUQ according to ASME standards is feasible but computationally expensive.

Applicability assessment for in-silico patient-specific TEVAR procedures

“…In particular, the assessment of the in-silico model applicability is a fundamental aspect to demonstrate the reliability of the model itself in a specified COU, as described in the step-by-step framework proposed by Pathmanathan et al, 2017. Among the literature, some studies carried out an exhaustive applicability analysis of the numerical model in different cardiovascular fields such as thrombectomy (Luraghi et al, 2021), cardiac electrophysiology (Pathmanathan and Gray, 2018), left ventricle blood flow after LVAD (Santiago et al, 2022) or haemolysis (Morrison et al, 2019). To the best of the authors' knowledge, this is the first study that investigates the applicability of the TEVAR numerical modeling, following the framework proposed by Pathmanathan et al, 2017. In this work, the finite element-based TEVAR procedure previously developed (Ramella et al, 2022) is successfully applied to a patient-specific aorta.…”

In Vitro Investigation of the Effect of the Timing of Left Ventricular Assist Device Speed Modulation on Intraventricular Flow Patterns

“…A similar flow topology has also been observed in previous studies using 2D echo color Doppler velocimetry in vivo , 25 ex vivo , 23 in vitro , 17,27 and in silico . 34 Consequently, optimizing LVAD speed to the patient, allowing the MV jet to fill the LV, is crucial to reduce high stagnation areas. In addition to its impact on LV flow patterns, a lower speed was found to promote AV opening, 35 reducing stagnation in the LVOT.…”

Fluid–structure interaction analysis of eccentricity and leaflet rigidity on thrombosis biomarkers in bioprosthetic aortic valve replacements

“…Second, the accuracy of the current model will be improved by including pre‐stresses, anisotropic models, the full TAVR geometry (including stent, cuffs and skirt), and aortic chamber deformation by coupling the immersed FSI with the ALE framework. Third, the model will be introduced in the verification, validation and uncertainty quantification (VVUQ) pipeline developed by the authors' research group 81 to exhaustively verify and validate this model against in silico experiments. Fourth, the heat valve model introduced here will be coupled to the existing fluid‐electro‐mechanical model of the human heart implemented in Alya 82 .…”