Performance assessment of an electrostatic filter-diverter stent cerebrovascular protection device. Is it possible not to use anticoagulants in atrial fibrilation elderly patients?

Stroke is the second leading cause of death worldwide. Nearly two-thirds of strokes are produced by cardioembolisms, and half of cardioembolic strokes are triggered by Atrial Fibrillation (AF), the most common type of arrhythmia. A more recent cause of cardioembolisms is Transcatheter Aortic Valve Replacements (TAVRs), which may onset post-procedural adverse events such as stroke and Silent Brain Infarcts (SBIs), for which no definitive treatment exists, and which will only get worse as TAVRs are implanted in younger and lower risk patients. It is well known that some specific characteristics of elderly patients may lower the safety and efficacy of anticoagulation therapy, making it a real urgency to find alternative therapies. We propose a device consisting of a strut structure placed at the base of the treated artery to model the potential risk of cerebral embolisms caused by dislodged debris of varying sizes. This work analyzes a design based on a patented medical device, intended to block cardioembolisms from entering the cerebrovascular system, with a particular focus on AF, and potentially TAVR patients. The study has been carried out in two stages. Both of them based on computational fluid dynamics (CFD) coupled with Lagrangian particle tracking method. The first stage of the work evaluates a variety of strut thicknesses and inter-strut spacings, contrasting with the device-free baseline geometry. The analysis is carried out by imposing flowrate waveforms characteristic of both healthy and AF patients. Boundary conditions are calibrated to reproduce physiological flowrates and pressures in a patient's aortic arch. In the second stage, the optimal geometric design from the first stage was employed, with the addition of lateral struts to prevent the filtration of particles and electronegatively charged strut surfaces, studying the effect of electrical forces on the clots if they are considered charged. Flowrate boundary conditions were used to emulate both healthy and AF conditions. Results from numerical simulations coming form the first stage indicate that the device blocks particles of sizes larger than the inter-strut spacing. It was found that lateral strut space had the highest impact on efficacy. Based on the results of the second stage, deploying the electronegatively charged device in all three aortic arch arteries, the number of particles entering these arteries was reduced on average by 62.6% and 51.2%, for the healthy and diseased models respectively, matching or surpassing current oral anticoagulant efficacy. In conclusion, the device demonstrated a two-fold mechanism for filtering emboli: while the smallest particles are deflected by electrostatic repulsion, avoiding microembolisms, which could lead to cognitive impairment, the largest ones are mechanically filtered since they cannot fit in between the struts, effectively blocking the full range of particle sizes analyzed in this study. The device presented in this manuscript offers an anticoagulant-free method to prevent stroke and SBIs, imperative given the growing population of AF and elderly patients.

Time-efficient three-dimensional transmural scar assessment provides relevant substrate characterization for ventricular tachycardia features and long-term recurrences in ischemic cardiomyopathy.

Delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging requires novel and time-efficient approaches to characterize the myocardial substrate associated with ventricular arrhythmia in patients with ischemic cardiomyopathy. Using a translational approach in pigs and patients with established myocardial infarction, we tested and validated a novel 3D methodology to assess ventricular scar using custom transmural criteria and a semiautomatic approach to obtain transmural scar maps in ventricular models reconstructed from both 3D-acquired and 3D-upsampled-2D-acquired LGE-CMR images. The results showed that 3D-upsampled models from 2D LGE-CMR images provided a time-efficient alternative to 3D-acquired sequences to assess the myocardial substrate associated with ischemic cardiomyopathy. Scar assessment from 2D-LGE-CMR sequences using 3D-upsampled models was superior to conventional 2D assessment to identify scar sizes associated with the cycle length of spontaneous ventricular tachycardia episodes and long-term ventricular tachycardia recurrences after catheter ablation. This novel methodology may represent an efficient approach in clinical practice after manual or automatic segmentation of myocardial borders in a small number of conventional 2D LGE-CMR slices and automatic scar detection.

In-silico human electro-mechanical ventricular modelling and simulation for drug-induced pro-arrhythmia and inotropic risk assessment.

Human-based computational modelling and simulation are powerful tools to accelerate the mechanistic understanding of cardiac patho-physiology, and to develop and evaluate therapeutic interventions. The aim of this study is to calibrate and evaluate human ventricular electro-mechanical models for investigations on the effect of the electro-mechanical coupling and pharmacological action on human ventricular electrophysiology, calcium dynamics, and active contraction. The most recent models of human ventricular electrophysiology, excitation-contraction coupling, and active contraction were integrated, and the coupled models were calibrated using human experimental data. Simulations were then conducted using the coupled models to quantify the effects of electro-mechanical coupling and drug exposure on electrophysiology and force generation in virtual human ventricular cardiomyocytes and tissue. The resulting calibrated human electro-mechanical models yielded active tension, action potential, and calcium transient metrics that are in agreement with experiments for endocardial, epicardial, and mid-myocardial human samples. Simulation results correctly predicted the inotropic response of different multichannel action reference compounds and demonstrated that the electro-mechanical coupling improves the robustness of repolarisation under drug exposure compared to electrophysiology-only models. They also generated additional evidence to explain the partial mismatch between in-silico and in-vitro experiments on drug-induced electrophysiology changes. The human calibrated and evaluated modelling and simulation framework constructed in this study opens new avenues for future investigations into the complex interplay between the electrical and mechanical cardiac substrates, its modulation by pharmacological action, and its translation to tissue and organ models of cardiac patho-physiology.