The Role of Patient-Specific Morphological Features of the Left Atrial Appendage on the Thromboembolic Risk Under Atrial Fibrillation.

Background: A large majority of thrombi causing ischemic complications under atrial fibrillation (AF) originate in the left atrial appendage (LAA), an anatomical structure departing from the left atrium, characterized by a large morphological variability between individuals. This work analyses the hemodynamics simulated for different patient-specific models of LAA by means of computational fluid-structure interaction studies, modeling the effect of the changes in contractility and shape resulting from AF. Methods: Three operating conditions were analyzed: sinus rhythm, acute atrial fibrillation, and chronic atrial fibrillation. These were simulated on four patient-specific LAA morphologies, each associated with one of the main morphological variants identified from the common classification: chicken wing, cactus, windsock, and cauliflower. Active contractility of the wall muscle was calibrated on the basis of clinical evaluations of the filling and emptying volumes, and boundary conditions were imposed on the fluid to replicate physiological and pathological atrial pressures, typical of the various operating conditions. Results: The LAA volume and shear strain rates were analyzed over time and space for the different models. Globally, under AF conditions, all models were well aligned in terms of shear strain rate values and predicted levels of risk. Regions of low shear rate, typically associated with a higher risk of a clot, appeared to be promoted by sudden bends and focused at the trabecule and the lobes. These become substantially more pronounced and extended with AF, especially under acute conditions. Conclusion: This work clarifies the role of active and passive contraction on the healthy hemodynamics in the LAA, analyzing the hemodynamic effect of AF that promotes clot formation. The study indicates that local LAA topological features are more directly associated with a thromboembolic risk than the global shape of the appendage, suggesting that more effective classification criteria should be identified.

A validated computational framework to predict outcomes in TAVI.

Transcatheter aortic valve implantation (TAVI) still presents complications: paravalvular leakage (PVL) and onset of conduction abnormalities leading to permanent pacemaker implantation. Our aim was testing a validated patient-specific computational framework for prediction of TAVI outcomes and possible complications. Twenty-eight TAVI patients (14 SapienXT and 14 CoreValve) were retrospectively selected. Pre-procedural CT images were post-processed to create 3D patient-specific implantation sites. The procedures were simulated with finite element analysis. Simulations' results were compared against post-procedural clinical fluoroscopy and echocardiography images. The computational model was in good agreement with clinical findings: the overall stent diameter difference was 2.6% and PVL was correctly identified with a post-processing algorithm in 83% of cases. Strains in the implantation site were studied to assess the risk of conduction system disturbance and were found highest in the patient who required pacemaker implantation. This study suggests that computational tool could support safe planning and broadening of TAVI.

Population-specific material properties of the implantation site for transcatheter aortic valve replacement finite element simulations.

Patient-specific computational models are an established tool to support device development and test under clinically relevant boundary conditions. Potentially, such models could be used to aid the clinical decision-making process for percutaneous valve selection; however, their adoption in clinical practice is still limited to individual cases. To be fully informative, they should include patient-specific data on both anatomy and mechanics of the implantation site. In this work, fourteen patient-specific computational models for transcatheter aortic valve replacement (TAVR) with balloon-expandable Sapien XT devices were retrospectively developed to tune the material parameters of the implantation site mechanical model for the average TAVR population. Pre-procedural computed tomography (CT) images were post-processed to create the 3D patient-specific anatomy of the implantation site. Balloon valvuloplasty and device deployment were simulated with finite element (FE) analysis. Valve leaflets and aortic root were modelled as linear elastic materials, while calcification as elastoplastic. Material properties were initially selected from literature; then, a statistical analysis was designed to investigate the effect of each implantation site material parameter on the implanted stent diameter and thus identify the combination of material parameters for TAVR patients. These numerical models were validated against clinical data. The comparison between stent diameters measured from post-procedural fluoroscopy images and final computational results showed a mean difference of 2.5 ±â€¯3.9%. Moreover, the numerical model detected the presence of paravalvular leakage (PVL) in 79% of cases, as assessed by post-TAVR echocardiographic examination. The final aim was to increase accuracy and reliability of such computational tools for prospective clinical applications.

Patient-specific simulations for planning treatment in congenital heart disease.

Patient-specific computational models have been extensively developed over the last decades and applied to investigate a wide range of cardiovascular problems. However, translation of these technologies into clinical applications, such as planning of medical procedures, has been limited to a few single case reports. Hence, the use of patient-specific models is still far from becoming a standard of care in clinical practice. The aim of this study is to describe our experience with a modelling framework that allows patient-specific simulations to be used for prediction of clinical outcomes. A cohort of 12 patients with congenital heart disease who were referred for percutaneous pulmonary valve implantation, stenting of aortic coarctation and surgical repair of double-outlet right ventricle was included in this study. Image data routinely acquired for clinical assessment were post-processed to set up patient-specific models and test device implantation and surgery. Finite-element and computational fluid dynamics analyses were run to assess feasibility of each intervention and provide some guidance. Results showed good agreement between simulations and clinical decision including feasibility, device choice and fluid-dynamic parameters. The promising results of this pilot study support translation of computer simulations as tools for personalization of cardiovascular treatments.

Computational modelling for congenital heart disease: how far are we from clinical translation?

Computational models of congenital heart disease (CHD) have become increasingly sophisticated over the last 20 years. They can provide an insight into complex flow phenomena, allow for testing devices into patient-specific anatomies (pre-CHD or post-CHD repair) and generate predictive data. This has been applied to different CHD scenarios, including patients with single ventricle, tetralogy of Fallot, aortic coarctation and transposition of the great arteries. Patient-specific simulations have been shown to be informative for preprocedural planning in complex cases, allowing for virtual stent deployment. Novel techniques such as statistical shape modelling can further aid in the morphological assessment of CHD, risk stratification of patients and possible identification of new 'shape biomarkers'. Cardiovascular statistical shape models can provide valuable insights into phenomena such as ventricular growth in tetralogy of Fallot, or morphological aortic arch differences in repaired coarctation. In a constant move towards more realistic simulations, models can also account for multiscale phenomena (eg, thrombus formation) and importantly include measures of uncertainty (ie, CIs around simulation results). While their potential to aid understanding of CHD, surgical/procedural decision-making and personalisation of treatments is undeniable, important elements are still lacking prior to clinical translation of computational models in the field of CHD, that is, large validation studies, cost-effectiveness evaluation and establishing possible improvements in patient outcomes.

Can finite element models of ballooning procedures yield mechanical response of the cardiovascular site to overexpansion?

Patient-specific numerical models could aid the decision-making process for percutaneous valve selection; in order to be fully informative, they should include patient-specific data of both anatomy and mechanics of the implantation site. This information can be derived from routine clinical imaging during the cardiac cycle, but data on the implantation site mechanical response to device expansion are not routinely available. We aim to derive the implantation site response to overexpansion by monitoring pressure/dimensional changes during balloon sizing procedures and by applying a reverse engineering approach using a validated computational balloon model. This study presents the proof of concept for such computational framework tested in-vitro. A finite element (FE) model of a PTS-X405 sizing balloon (NuMed, Inc., USA) was created and validated against bench tests carried out on an ad hoc experimental apparatus: first on the balloon alone to replicate free expansion; second on the inflation of the balloon in a rapid prototyped cylinder with material deemed suitable for replicating pulmonary arteries in order to validate balloon/implantation site interaction algorithm. Finally, the balloon was inflated inside a compliant rapid prototyped patient-specific right ventricular outflow tract to test the validity of the approach. The corresponding FE simulation was set up to iteratively infer the mechanical response of the anatomical model. The test in this simplified condition confirmed the feasibility of the proposed approach and the potential for this methodology to provide patient-specific information on mechanical response of the implantation site when overexpanded, ultimately for more realistic computational simulations in patient-specific settings.

Numerical model of a valvuloplasty balloon: in vitro validation in a rapid-prototyped phantom.

BACKGROUND: Patient-specific simulations can provide insight into the mechanics of cardiovascular procedures. Amongst cardiovascular devices, non-compliant balloons are used in several minimally invasive procedures, such as balloon aortic valvuloplasty. Although these balloons are often included in the computer simulations of these procedures, validation of the balloon behaviour is often lacking. We therefore aim to create and validate a computational model of a valvuloplasty balloon. METHODS: A finite element (FE) model of a valvuloplasty balloon (Edwards 9350BC23) was designed, including balloon geometry and material properties from tensile testing. Young's Modulus and distensibility of different rapid prototyping (RP) rubber-like materials were evaluated to identify the most suitable compound to reproduce the mechanical properties of calcified arteries in which such balloons are likely to be employed clinically. A cylindrical, simplified implantation site was 3D printed using the selected material and the balloon was inflated inside it. The FE model of balloon inflation alone and its interaction with the cylinder were validated by comparison with experimental Pressure-Volume (P-V) and diameter-Volume (d-V) curves. RESULTS: Root mean square errors (RMSE) of pressure and diameter were RMSE P = 161.98 mmHg (3.8 % of the maximum pressure) and RMSE d = 0.12 mm (<0.5 mm, within the acquisition system resolution) for the balloon alone, and RMSE P = 94.87 mmHg (1.9 % of the maximum pressure) and RMSE d = 0.49 mm for the balloon inflated inside the simplified implantation site, respectively. CONCLUSIONS: This validated computational model could be used to virtually simulate more realistic valvuloplasty interventions.

Patient-specific finite element models to support clinical decisions: A lesson learnt from a case study of percutaneous pulmonary valve implantation.

OBJECTIVES AND BACKGROUND: Patient-specific finite element (FE) simulations were used to assess different transcatheter valve devices and help select the most appropriate treatment strategy for a patient (17-year-old male) with borderline dimensions for Melody® percutaneous pulmonary valve implantation (PPVI). METHODS AND RESULTS: Patient-specific implantation site morphology was derived from cardiovascular magnetic resonance (CMR) images along with the implantation site mechanical behavior by coupling systolic/diastolic dimensions and the pressure gradient in a linear elastic model, and iterative tuning. In this way, the model accounted for the mechanical response not only of the arterial wall, but also of the surrounding tissue. Four stents (2 balloon-expandable including prestenting and 2 self-expandable) were virtually implanted and the stent final configuration, anchoring, migration forces, arterial wall stresses, paravalvular regurgitation, and device mechanical performance were evaluated. A Sapien29 device with prestenting was indicated as the optimal approach for this specific patient as it had a fully open valve, safe anchoring along the entire circumference, low risk of paravalvular leak, and arterial rupture. However, at the time of the PPVI procedure, after balloon sizing, device implantation was suspended due to perceived high risk of device embolization. CONCLUSIONS: FE analysis allows a comparison between different treatment scenarios to add information to the clinical decision making process. However, further studies are required to fully predict patient-specific response to stenting and therefore true clinical outcomes.