scholarly journals Arrhythmogenic Effects of Genetic Mutations Affecting Potassium Channels in Human Atrial Fibrillation: A Simulation Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Rebecca Belletti ◽  
Lucia Romero ◽  
Laura Martinez-Mateu ◽  
Elizabeth M. Cherry ◽  
Flavio H. Fenton ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Pulmonary Vein ◽  
Protein Structures ◽  
Spiral Wave ◽  
Ionic Currents ◽  
Patient Specific ◽  
Genetic Mutations ◽  
Asymptomatic Patients ◽  
Arrhythmogenic Substrate

Genetic mutations in genes encoding for potassium channel protein structures have been recently associated with episodes of atrial fibrillation in asymptomatic patients. The aim of this study is to investigate the potential arrhythmogenicity of three gain-of-function mutations related to atrial fibrillation—namely, KCNH2 T895M, KCNH2 T436M, and KCNE3-V17M—using modeling and simulation of the electrophysiological activity of the heart. A genetic algorithm was used to tune the parameters’ value of the original ionic currents to reproduce the alterations experimentally observed caused by the mutations. The effects on action potentials, ionic currents, and restitution properties were analyzed using versions of the Courtemanche human atrial myocyte model in different tissues: pulmonary vein, right, and left atrium. Atrial susceptibility of the tissues to spiral wave generation was also investigated studying the temporal vulnerability. The presence of the three mutations resulted in an overall more arrhythmogenic substrate. Higher current density, action potential duration shortening, and flattening of the restitution curves were the major effects of the three mutations at the single-cell level. The genetic mutations at the tissue level induced a higher temporal vulnerability to the rotor’s initiation and progression, by sustaining spiral waves that perpetuate until the end of the simulation. The mutation with the highest pro-arrhythmic effects, exhibiting the widest sustained VW and the smallest meandering rotor’s tip areas, was KCNE3-V17M. Moreover, the increased susceptibility to arrhythmias and rotor’s stability was tissue-dependent. Pulmonary vein tissues were more prone to rotor’s initiation, while in left atrium tissues rotors were more easily sustained. Re-entries were also progressively more stable in pulmonary vein tissue, followed by the left atrium, and finally the right atrium. The presence of the genetic mutations increased the susceptibility to arrhythmias by promoting the rotor’s initiation and maintenance. The study provides useful insights into the mechanisms underlying fibrillatory events caused by KCNH2 T895M, KCNH2 T436M, and KCNE3-V17M and might aid the planning of patient-specific targeted therapies.

scholarly journals Anatomical correlation between left atrium pulmonary vein ablation targets of atrial fibrillation and adjacent bronchi and pulmonary arteries by MSCT

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yan-Jing Wang ◽  
Huan Sun ◽  
Xiao-Fei Fan ◽  
Meng-Chao Zhang ◽  
Ping Yang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Pulmonary Vein ◽  
Pulmonary Arteries ◽  
Contact Points ◽  
Pulmonary Vein Ablation ◽  
Adjacent Structures ◽  
Anatomical Correlation ◽  
The Right

Abstract Background The ablation targets of atrial fibrillation (AF) are adjacent to bronchi and pulmonary arteries (PAs). We used computed tomography (CT) to evaluate the anatomical correlation between left atrium (LA)-pulmonary vein (PV) and adjacent structures. Methods Data were collected from 126 consecutive patients using coronary artery CT angiography. The LA roof was divided into three layers and nine points. The minimal spatial distances from the nine points and four PV orifices to the adjacent bronchi and PAs were measured. The distances from the PV orifices to the nearest contact points of the PVs, bronchi, and PAs were measured. Results The anterior points of the LA roof were farther to the bronchi than the middle or posterior points. The distances from the nine points to the PAs were shorter than those to the bronchi (5.19 ± 3.33 mm vs 8.62 ± 3.07 mm; P < .001). The bilateral superior PV orifices, especially the right superior PV orifices were closer to the PAs than the inferior PV orifices (left superior PV: 7.59 ± 4.14 mm; right superior PV: 4.43 ± 2.51 mm; left inferior PV: 24.74 ± 5.26 mm; right inferior PV: 22.33 ± 4.75 mm) (P < .001). Conclusions The right superior PV orifices were closer to the bronchi and PAs than other PV orifices. The ablation at the mid-posterior LA roof had a higher possibility to damage bronchi. CT is a feasible method to assess the anatomical adjacency in vivo, which might provide guidance for AF ablation.

scholarly journals Computational Analysis of Mapping Catheter Geometry and Contact Quality Effects on Rotor Detection in Atrial Fibrillation

2021 ◽  
Vol 12 ◽  
Author(s):  
Chiara Bartolucci ◽  
Claudio Fabbri ◽  
Corrado Tomasi ◽  
Paolo Sabbatani ◽  
Stefano Severi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Structural Parameters ◽  
Spiral Wave ◽  
Spatial Location ◽  
Electrode Spacing ◽  
Patient Specific ◽  
Electrode Distance ◽  
Detection Failure ◽  
Distance Position ◽  
Mapping Catheter

Atrial fibrillation (AF) is the most common cardiac arrhythmia and catheter mapping has been proved to be an effective approach for detecting AF drivers to be targeted by ablation. Among drivers, the so-called rotors have gained the most attention: their identification and spatial location could help to understand which patient-specific mechanisms are acting, and thus to guide the ablation execution. Since rotor detection by multi-electrode catheters may be influenced by several structural parameters including inter-electrode spacing, catheter coverage, and endocardium-catheter distance, in this study we proposed a tool for testing the ability of different catheter shapes to detect rotors in different conditions. An approach based on the solution of the monodomain equations coupled with a modified Courtemanche ionic atrial model, that considers an electrical remodeling, was applied to simulate spiral wave dynamics on a 2D model for 7.75 s. The developed framework allowed the acquisition of unipolar signals at 2 KHz. Two high-density multipolar catheters were simulated (Advisor™ HD Grid and PentaRay®) and placed in a 2D region in which the simulated spiral wave persists longer. The configuration of the catheters was then modified by changing the number of electrodes, inter-electrodes distance, position, and atrial-wall distance for assessing how they would affect the rotor detection. In contact with the wall and at 1 mm distance from it, all the configurations detected the rotor correctly, irrespective of geometry, coverage, and inter-electrode distance. In the HDGrid-like geometry, the increase of the inter-electrode distance from 3 to 6 mm caused rotor detection failure at 2 mm distance from the LA wall. In the PentaRay-like configuration, regardless of inter-electrode distance, rotor detection failed at 3 mm endocardium-catheter distance. The asymmetry of this catheter resulted in rotation-dependent rotor detection. To conclude, the computational framework we developed is based on realistic catheter shapes designed with parameter configurations which resemble clinical settings. Results showed it is well suited to investigate how mapping catheter geometry and location affect AF driver detection, therefore it is a reliable tool to design and test new mapping catheters.

P1415Wide antral circumferential pulmonary vein isolation ablation using a novel balloon cryoablation catheter

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A P Martin ◽  
M Fowler ◽  
N Lever
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Pulmonary Vein ◽  
Pulmonary Vein Isolation ◽  
Paroxysmal Atrial Fibrillation ◽  
Left Atrial ◽  
Pulmonary Veins ◽  
Posterior Wall ◽  
The Novel ◽  
Median Treatment

Abstract Background Pulmonary vein isolation using cryotherapy is an established treatment for the management of patients with paroxysmal atrial fibrillation. Ablation using the commercially available balloon cryocatheter has been shown to create wide antral pulmonary vein isolation. A novel balloon cryocatheter (BCC) has been designed to maintain uniform pressure and size during ablation, potentially improving contact with the antral anatomy. The extent of ablation created using the novel BCC has not previously been established. Purpose To determine the anatomical extent of pulmonary vein isolation using electroanatomical mapping when performing catheter ablation for paroxysmal atrial fibrillation using the novel BCC. Methods Nine consecutive patients underwent pre-procedure computed tomography angiography of the left atrium to quantify the chamber dimensions. An electroanatomical map was created using the cryoablation system mapping catheter and a high definition mapping system. A bipolar voltage map was obtained following ablation to determine the extent of pulmonary vein isolation ablation. A volumetric technique was used to quantify the extent of vein and posterior wall electrical isolation in addition to traditional techniques for proving entrance and exit block. Results All patients had paroxysmal atrial fibrillation, mean age 56 years, 7 (78%) male. Electrical isolation was achieved for 100% of the pulmonary veins; mean total procedure time was 109 min (+/- 26 SD), and fluoroscopy time 14.9 min (+/- 2.4 SD). The median treatment applications per vein was one (range one - four), and median treatment duration 180 sec (range 180 -240). Left atrial volume 32 mL/m2 (+/- 7 SD), and mean left atrial posterior wall area 22 cm2 (+/- 4 SD). Data was available for quantitative assessment of the extent of ablation for eight patients. No lesions (0 of 32) were ostial in nature. The antral surface area of ablation was not statistically different between the left and right sided pulmonary veins (p 0.63), which were 5.9 (1.6 SD) and 5.4 (2.1 SD) cm2 respectively. In total 50% of the posterior left atrial wall was ablated.  Conclusion Pulmonary vein isolation using a novel BCC provides a wide and antral lesion set. There is significant debulking of the posterior wall of the left atrium. Abstract Figure.

A Proof of Concept for Computational Fluid Dynamic Analysis of the Left Atrium in Atrial Fibrillation on a Patient-Specific Basis

2019 ◽  
Vol 142 (1) ◽  
Author(s):  
Alessandro Masci ◽  
Martino Alessandrini ◽  
Davide Forti ◽  
Filippo Menghini ◽  
Luca Dedé ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Stratification ◽  
Left Atrium ◽  
Stroke Risk ◽  
Fluid Dynamic ◽  
Blood Stasis ◽  
Patient Specific ◽  
Computational Fluid Dynamic Analysis ◽  
Cerebrovascular Events ◽  
Hemodynamic Information

Abstract Atrial fibrillation (AF) is associated with a fivefold increase in the risk of cerebrovascular events, being responsible of 15–18% of all strokes. The morphological and functional remodeling of the left atrium (LA) caused by AF favors blood stasis and, consequently, stroke risk. In this context, several clinical studies suggest that the stroke risk stratification could be improved by using hemodynamic information on the LA and the left atrial appendage (LAA). The goal of this study was to develop a personalized computational fluid dynamics (CFD) model of the LA which could clarify the hemodynamic implications of AF on a patient-specific basis. In this paper, we present the developed model and its application to two AF patients as a preliminary advancement toward an optimized stroke risk stratification pipeline.

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