Verification and validation pipeline for the risk-informed credibility assessment of in-silico fluid simulations for left atrial appendage devices
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The implantation of left atrial appendage occluder (LAAO) devices is an efficient therapy to reduce the risk of thrombus formation in atrial fibrillation patients with contraindications to standard anticoagulant therapy. Clinicians need to personalise the type, size, and the position implantation of the LAAO device for each patient due to the high morphological and variability of the left atrial appendage. Medical imaging modalities such as X-ray, echocardiography, and Computerised Tomography, are mainly used for pre-operative planning, intervention guidance and patient follow-up in LAAO interventions. Most parameters extracted from the medical images are focused on the LAA morphology, with limited information (usually from 2D Doppler acquisitions) on blood flow patterns. However, haemodynamics play a key role in thrombus formation, with low blood flow velocities and complex recirculation being associated with high thrombogenic risk. Device-related thrombus may also appear after the implantation of a LAAO device. In-silico models can provide added value for the LAAO-related medical decisions, with fluid simulations, before and after implantation, being used to optimise device design, personalise device settings and tailor patient follow-up therapy. Despite several LAA-based fluid models available in the literature, which are usually applied on a limited number of patient-specific geometries, there is a lack of consensus on the most appropriate set of boundary conditions to generate realistic simulations. Systematic verification and validation studies, following the ASME V&V40 guidelines with in-vitro and/or ex-vivo data, are also missing. Therefore, there is a need for building credibility of LAAO-based in-silico models to integrate them as part of the medical device certification procedures by organisms such as the FDA. In this work, we present an overview of the state of the art in LAA-based fluid simulations and define the required steps to establish, plan and assess risk-informed credibility of in-silico models specific to left atrial appendage occluder devices. The most relevant questions of interest and contexts of use were jointly decided by academic, industrial, and clinical stakeholders. Additionally, the available data for verification and validation (including uncertainty quantification) purposes is described, as well as a thorough model risk analysis and the link to in-silico clinical trials.
