Dataset Information

Image-Based Computational Evaluation of the Effects of Atrial Wall Thickness and Fibrosis on Re-entrant Drivers for Atrial Fibrillation.

ABSTRACT: Introduction: Catheter ablation (CA) is a common treatment for atrial fibrillation (AF), but the knowledge of optimal ablation sites, and hence clinical outcomes, are suboptimal. Increasing evidence suggest that ablation strategies based on patient-specific substrates information, such as distributions of fibrosis and atrial wall thickness (AWT), may be used to improve therapy. We hypothesized that competing influences of large AWT gradients and fibrotic patches on conductive properties of atrial tissue can determine locations of re-entrant drivers (RDs) sustaining AF. Methods: Two sets of models were used: (1) a simple model of 3D atrial tissue slab with a step change in AWT and a synthetic fibrosis patch, and (2) 3D models based on patient-specific right atrial (RA) and left atrial (LA) geometries. The latter were obtained from four healthy volunteers and two AF patients, respectively, using magnetic resonance imaging (MRI). A synthetic fibrotic patch was added in the RA and fibrosis distributions in the LA were obtained from gadolinium-enhanced MRI of the same patients. In all models, 3D geometry was combined with the Fenton-Karma atrial cell model to simulate RDs. Results: In the slab, RDs drifted toward, and then along the AWT step. However, with additional fibrosis, the RDs were localized in regions between the step and fibrosis. In the RA, RDs drifted toward and anchored to a large AWT gradient between the crista terminalis (CT) region and the surrounding atrial wall. Without such a gradient, RDs drifted toward the superior vena cava (SVC) or the tricuspid valve (TSV). With additional fibrosis, RDs initiated away from the CT anchored to the fibrotic patch, whereas RDs initiated close to the CT region remained localized between the two structures. In the LA, AWT was more uniform and RDs drifted toward the pulmonary veins (PVs). However, with additional fibrotic patches, RDs either anchored to them or multiplied. Conclusion: In the RA, RD locations are determined by both fibrosis and AWT gradients at the CT region. In the LA, they are determined by fibrosis due to the absence of large AWT gradients. These results elucidate mechanisms behind the stabilization of RDs sustaining AF and can help guide ablation therapy.

SUBMITTER: Roy A

PROVIDER: S-EPMC6187302 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Image-Based Computational Evaluation of the Effects of Atrial Wall Thickness and Fibrosis on Re-entrant Drivers for Atrial Fibrillation.

Roy Aditi A Varela Marta M Aslanidi Oleg O

Frontiers in physiology 20181004

<b>Introduction:</b> Catheter ablation (CA) is a common treatment for atrial fibrillation (AF), but the knowledge of optimal ablation sites, and hence clinical outcomes, are suboptimal. Increasing evidence suggest that ablation strategies based on patient-specific substrates information, such as distributions of fibrosis and atrial wall thickness (AWT), may be used to improve therapy. We hypothesized that competing influences of large AWT gradients and fibrotic patches on conductive properties o ...[more]

PMID: 30349483

Similar Datasets

Project description:Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF.

Project description:OBJECTIVES:This study sought to assess the relationship between fibrosis and re-entrant activity in persistent atrial fibrillation (AF). BACKGROUND:The mechanisms involved in sustaining re-entrant activity during AF are poorly understood. METHODS:Forty-one patients with persistent AF (age 56 ± 12 years; 6 women) were evaluated. High-resolution electrocardiographic imaging (ECGI) was performed during AF by using a 252-chest electrode array, and phase mapping was applied to locate re-entrant activity. Sites of high re-entrant activity were defined as re-entrant regions. Late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) was performed at 1.25 × 1.25 × 2.5 mm resolution to characterize atrial fibrosis and measure atrial volumes. The relationship between LGE burden and the number of re-entrant regions was analyzed. Local LGE density was computed and characterized at re-entrant sites. All patients underwent catheter ablation targeting re-entrant regions, the procedural endpoint being AF termination. Clinical, CMR, and ECGI predictors of acute procedural success were then analyzed. RESULTS:Left atrial (LA) LGE burden was 22.1 ± 5.9% of the wall, and LA volume was 74 ± 21 ml/m2. The number of re-entrant regions was 4.3 ± 1.7 per patient. LA LGE imaging was significantly associated with the number of re-entrant regions (R = 0.52, p = 0.001), LA volume (R = 0.62, p < 0.0001), and AF duration (R = 0.54, p = 0.0007). Regional analysis demonstrated a clustering of re-entrant activity at LGE borders. Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas (p < 0.0001). Failure to achieve AF termination during ablation was associated with higher LA LGE burden (p < 0.001), higher number of re-entrant regions (p < 0.001), and longer AF duration (p = 0.008). CONCLUSIONS:The number of re-entrant regions during AF relates to the extent of LGE on CMR, with the location of these regions clustering to LGE areas. These characteristics affect procedural outcomes of ablation.

Dataset Information

Image-Based Computational Evaluation of the Effects of Atrial Wall Thickness and Fibrosis on Re-entrant Drivers for Atrial Fibrillation.

Publications

Image-Based Computational Evaluation of the Effects of Atrial Wall Thickness and Fibrosis on Re-entrant Drivers for Atrial Fibrillation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets