909 research outputs found

    Application of Numerical Simulation in Cardiovascular Medicine

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    Introduction: The purpose of this thesis is to study atherosclerotic risk and thrombotic risk through application of numerical simulation to cardiovascular geometry and morphology. This has been applied to two specific situations, the angle of take-off of the left main coronary artery and the morphology of the left atrial appendage. A. The distribution of atherosclerotic plaque and the plaque rupture rate in isolated left main coronary disease is different to that seen in left main disease with multi-vessel disease, suggesting local biomechanical forces play an important part in governing plaque formation and rupture. The varying vertical left main coronary artery take-off angulation may impact on the wall shear stress. B. Different left atrial appendage morphologies seem to have different risk of thromboembolism, in patients with atrial fibrillation and low CHADS2 VASC score. From this observation, it can be hypothesized that left atrial morphology subtype with a more complex structure can lead to higher volume of blood stagnation. Aim: A. To investigate the effects of vertical take-off angulation of the left main coronary artery from aorta and varying stenosis severities on wall shear stress in the left main coronary artery. B. To investigate the impact of different left atrial appendage morphologies on slow vortical flow estimated by flow dynamics. Methods: A. Artificially created and patient-specific computed tomography-derived 3-dimensional digital models of the left main coronary artery with varying vertical take-off angulation and artery stenoses were generated. These were exported for numerical simulation to calculate the wall shear stress values and mapping in each model set. B. Patient-specific computed tomography-derived 3-dimensional digital model sets of different left atrial appendage morphologies were exported for numerical simulation to calculate the volume and distribution of slow vortical flow. Left atrial appendage emptying was assessed. Results: A. The study of left main take off demonstrated that the preferred development site of atherosclerotic plaques in pathological studies corresponds to regions of low wall shear stress. Both peak wall shear stress and mean wall shear stress increased with more vertical take-off, and this relationship was accentuated by increasing stenosis severity. The more vertically angled LMCA take-off from aorta in the presence of significant stenosis severity was also associated with a larger area of low wall shear stress. These findings may explain the higher atherosclerotic plaque rupture rate and higher percentage of proximally located plaque seen in isolated left main coronary artery disease B. For complex geometry, the Cauliflower left atrial appendage subtype contained the greatest volume of slow vortical flow at low shear rate across a range of different left atrial appendage emptying velocities. This rheological mechanistic observation correlates well with the clinical observation that the highest rate of clinical thromboembolism is seen with the Cauliflower subtype in patients with low CHADS2 VASC score atrial fibrillation. However, in the presence of severely depressed left atrial appendage function differences between left atrial appendage morphology subtypes diminish. Conclusion: A. LMCA angulation may be an additional important factor to be considered in the clinical evaluation of the pathogenesis and progression of LMCA atheromatous disease. B. Stasis of blood, assessed in this study by the volume of slow vortical flow, is shown to depend on left atrial appendage morphology, and also depends on left atrial appendage function/emptying velocity. Under conditions when function is mildly to moderately reduced, then it is likely that morphology is an important variable

    Anatomical targets and expected outcomes of catheter-based ablation of atrial fibrillation in 2020.

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    Anatomical-based approaches, targeting either pulmonary vein isolation (PVI) or additional extra PV regions, represent the most commonly used ablation treatments in symptomatic patients with atrial fibrillation (AF) recurrences despite antiarrhythmic drug therapy. PVI remains the main anatomical target during catheter-based AF ablation, with the aid of new technological advances as contact force monitoring to increase safety and effective radiofrequency (RF) lesions. Nowadays, cryoballoon ablation has also achieved the same level of scientific evidence in patients with paroxysmal AF undergoing PVI. In parallel, electrical isolation of extra PV targets has progressively increased, which is associated with a steady increase in complex cases undergoing ablation. Several atrial regions as the left atrial posterior wall, the vein of Marshall, the left atrial appendage, or the coronary sinus have been described in different series as locations potentially involved in AF initiation and maintenance. Targeting these regions may be challenging using conventional point-by-point RF delivery, which has opened new opportunities for coadjuvant alternatives as balloon ablation or selective ethanol injection. Although more extensive ablation may increase intraprocedural AF termination and freedom from arrhythmias during the follow-up, some of the targets to achieve such outcomes are not exempt of potential severe complications. Here, we review and discuss current anatomical approaches and the main ablation technologies to target atrial regions associated with AF initiation and maintenance.This work was supported by the European Regional Development Fund, the Spanish Ministry of Science and Innovation (SAF2016- 80324-R), and the FundaciĂłn Interhospitalaria para la InvestigaciĂłn Cardiovascular (FIC). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Science and Innovation and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Giulio La Rosa has received a fellowship grant from the joint program between the Heart Rhythm Association of the Spanish Society of Cardiology (ARC) and CNIC.S

    Pathophysiology of atrial fibrillation: From initiation to maintenance

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    Atrial fibrillation (AF) is the most common arrhythmia in adults; it affects approximately 0.8 million patients in Japan alone. Yet despite many years of basic and clinical research, the exact mechanisms underlying the initiation and maintenance of AF remain poorly understood. In this review article, we summarize recent high‐resolution optical mapping studies in isolated sheep hearts, which have provided new insights into the dynamics and mechanisms of AF. We focus on 3 models of AF. First, we discuss results from experiments on AF induced by atrial stretch that revealed the presence of spatio‐temporally organized waves emerging from the posterior wall of the left atrium. In the presence of adreno‐cholinergic stimulation and stretch, AF was governed by evolving interactions between reentry and spontaneous focal discharges. Next, we outline the results obtained from a persistent AF model (average AF duration: 21.3 day) induced by intermittent rapid atrial pacing. By using simultaneous optical mapping of epicardial and endocardial activation patterns, we demonstrated that AF in this model was maintained by 3‐dimensional scroll waves with I‐shaped filaments anchored to junctions between thin and thick myocardium. Numerical simulation results predicted that wall thickness‐dependent activation of stretch‐activated channels and the filament tension dynamics were sufficient to explain the specific localization of the I‐shaped filament. In a final set of studies discussed herein, we investigated AF in sheep with tachypacing‐induced heart failure and found that micro‐reentry in the left atria was a major mechanism of AF maintenance, although focal discharges at the pulmonary vein area also played a role. Large fibrotic patches in failing hearts may serve as potential anchoring sites for micro‐reentry in this model. Thus, the 3 different experimental results in isolated sheep hearts presented here clearly suggest that self‐sustained rotors do exist in the atria and that such rotors are in fact the high frequency sources that determine the complex patterns of activation that characterize AF.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142071/1/joa3129.pd

    Interventional techniques in the management of persistent atrial fibrillation

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    Atrial fibrillation (AF) is a common cardiac rhythm problem experienced by patients and comprises an increasing demand on healthcare systems. AF is characterised by advanced neurohormonal remodelling in the atria resulting in dilation and variable degree of atrial fibrosis that can be measured by imaging techniques with difficulty in developing methods of identifying and quantifying left atrial (LA) fibrosis. LA fibrosis can be estimated by measuring LA scar using non-invasive imaging methods such as strain imaging in advanced echocardiography and in cardiac magnetic resonance (CMR) imaging. Achieving rhythm control strategy utilising catheter ablation (CA) has shown to be advantageous in improving quality of life (QOL) in patients with paroxysmal AF. The most effective method in management of AF has remained elusive in non-paroxysmal AF. Thoracoscopic surgical ablation (TSA) has been developed over the last decade by experienced surgeons with some promising early results but has not been investigated in long-standing persistent AF (LSPAF). I have attempted to answer some of the relevant questions that have remained in management of LSPAF by conducting a multicentre randomised control trial comparing efficacy between CA and TSA (CASA-AF RCT) and improvements in quality of life indices. In a sub-study, I measured LA volumes using echocardiography and CMR to determine reverse remodelling and LA function using tissue Doppler imaging and strain imaging to predict AF recurrence. In a CMR sub-study, a novel automatic LA segmentation algorithm was used to quantify LA fibrosis before and after ablation. I was able to quantify the response of the autonomic nervous system to targeted ganglionic plexi (GP) ablation as part of TSA compared to CA by measuring heart rate variability. I am hopeful that the knowledge gained from this thesis will help with an appropriate selection that will improve the management of patients with LSPAF.Open Acces

    A 3-Dimensional In Silico Test Bed for Radiofrequency Ablation Catheter Design Evaluation and Optimization

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    Atrial fibrillation (AF) is the disordered activation of the atrial myocardium, which is a major cause of stroke. Currently, the most effective, minimally traumatic treatment for AF is percutaneous catheter ablation to isolate arrhythmogenic areas from the rest of the atrium. The standard in vitro evaluation of ablation catheters through lesion studies is a resource intensive effort due to tissue variability and visual measurement methods, necessitating large sample sizes and multiple prototype builds. A computational test bed for ablation catheter evaluation was built in SolidWorksÂź using the morphology and dimensions of the left atrium adjacent structures. From this geometry, the physical model was built in COMSOL MultiphysicsÂź, where a combination of the laminar fluid flow, electrical currents, and bioheat transfer was used to simulate radiofrequency (RF) tissue ablation. Simulations in simplified 3D geometries led to lesions sizes within the reported ranges from an in-vivo ablation study. However, though the ellipsoid lesion morphologies in the full atrial model were consistent with past lesion studies, perpendicularly oriented catheter tips were associated with decreases of -91.3% and -70.0% in lesion depth and maximum diameter. On the other hand, tangentially oriented catheter tips produced lesions that were only off by -28.4% and +7.9% for max depth and max diameter. Preliminary investigation into the causes of the discrepancy were performed for fluid velocities, contact area, and other factors. Finally, suggestions for further investigation are provided to aid in determining the root cause of the discrepancy, such that the test bed may be used for other ablation catheter evaluations
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