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      Proximity to the descending aorta predicts regional fibrosis in the adjacent left atrial wall: aetiopathogenic and prognostic implications

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          Abstract

          Aims

          Left atrial (LA) fibrosis is present in patients with atrial fibrillation (AF) and can be visualized by magnetic resonance imaging with late gadolinium enhancement (LGE-MRI). Previous studies have shown that LA fibrosis is not randomly distributed, being more frequent in the area adjacent to the descending aorta (DAo). The objective of this study is to analyse the relationship between fibrosis in the atrial area adjacent to the DAo and the distance to it, as well as the prognostic implications of this fibrosis.

          Methods and results

          Magnetic resonance imaging with late gadolinium enhancement was obtained in 108 patients before AF ablation to analyse the extent of LA fibrosis and the distance DAo-to-LA. A high-density electroanatomic map was performed in a subgroup of 16 patients to exclude the possibility of an MRI artifact. Recurrences after ablation were analysed at 1 year of follow-up. The extent of atrial fibrosis in the area adjacent to the DAo was inversely correlated with the distance DAo-to-LA (r = −0.34, P < 0.001). This area had the greatest intensity of LGE [image intensity ratio (IIR) 1.14 ± 0.15 vs. 0.99 ± 0.16; P < 0.001] and also the lowest voltage (1.07 ± 0.86 vs. 1.54 ± 1.07 mV; P < 0.001) and conduction velocity (0.65 ± 0.06 vs. 0.96 ± 0.57 mm/ms; P < 0.001). The extent of this regional fibrosis predicted recurrence after AF ablation [hazard ratio (HR) 1.02, 95% CI 1.01–1.03; P = 0.01], however total fibrosis did not (HR = 1.01, 95% CI 0.97–1.06, P = 0.54).

          Conclusions

          Atrial fibrosis was predominantly located in the area adjacent to the DAo, and increased with the proximity between the two structures. Furthermore, this regional fibrosis better predicted recurrence after AF ablation than total atrial fibrosis.

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          Most cited references21

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          Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study.

          Left atrial fibrosis is prominent in patients with atrial fibrillation (AF). Extensive atrial tissue fibrosis identified by delayed enhancement magnetic resonance imaging (MRI) has been associated with poor outcomes of AF catheter ablation. To characterize the feasibility of atrial tissue fibrosis estimation by delayed enhancement MRI and its association with subsequent AF ablation outcome. Multicenter, prospective, observational cohort study of patients diagnosed with paroxysmal and persistent AF (undergoing their first catheter ablation) conducted between August 2010 and August 2011 at 15 centers in the United States, Europe, and Australia. Delayed enhancement MRI images were obtained up to 30 days before ablation. Fibrosis quantification was performed at a core laboratory blinded to the participating center, ablation approach, and procedure outcome. Fibrosis blinded to the treating physicians was categorized as stage 1 (<10% of the atrial wall), 2 (≥10%-<20%), 3 (≥20%-<30%), and 4 (≥30%). Patients were followed up for recurrent arrhythmia per current guidelines using electrocardiography or ambulatory monitor recording and results were analyzed at a core laboratory. Cumulative incidence of recurrence was estimated by stage at days 325 and 475 after a 90-day blanking period (standard time allowed for arrhythmias related to ablation-induced inflammation to subside) and the risk of recurrence was estimated (adjusting for 10 demographic and clinical covariates). Atrial tissue fibrosis estimation by delayed enhancement MRI was successfully quantified in 272 of 329 enrolled patients (57 patients [17%] were excluded due to poor MRI quality). There were 260 patients who were followed up after the blanking period (mean [SD] age of 59.1 [10.7] years, 31.5% female, 64.6% with paroxysmal AF). For recurrent arrhythmia, the unadjusted overall hazard ratio per 1% increase in left atrial fibrosis was 1.06 (95% CI, 1.03-1.08; P < .001). Estimated unadjusted cumulative incidence of recurrent arrhythmia by day 325 for stage 1 fibrosis was 15.3% (95% CI, 7.6%-29.6%); stage 2, 32.6% (95% CI, 24.3%-42.9%); stage 3, 45.9% (95% CI, 35.5%-57.5%); and stage 4, 51.1% (95% CI, 32.8%-72.2%) and by day 475 was 15.3% (95% CI, 7.6%-29.6%), 35.8% (95% CI, 26.2%-47.6%), 45.9% (95% CI, 35.6%-57.5%), and 69.4% (95% CI, 48.6%-87.7%), respectively. Similar results were obtained after covariate adjustment. The addition of fibrosis to a recurrence prediction model that includes traditional clinical covariates resulted in an improved predictive accuracy with the C statistic increasing from 0.65 to 0.69 (risk difference of 0.05; 95% CI, 0.01-0.09). Among patients with AF undergoing catheter ablation, atrial tissue fibrosis estimated by delayed enhancement MRI was independently associated with likelihood of recurrent arrhythmia. The clinical implications of this association warrant further investigation.
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            Structural abnormalities in atrial walls are associated with presence and persistency of atrial fibrillation but not with age.

            The purpose of this study was to assess the association between structural changes in human atria, age, and history of atrial fibrillation (AF). Development of fibrosis in atrial walls is associated with deterioration of atrial conduction and predisposes to AF in experiment. Human data, however, are scarce, and whether fibrosis is a cause or consequence of AF is not known. Medical records for consecutive autopsies were checked for AF history and duration. Atrial specimens from 30 patients (ages 64 ± 12 years) were collected in 3 equal age-matched groups as patients without AF history, with paroxysmal AF, or with permanent AF. Tissue samples were obtained at the level of superior pulmonary veins, inferior pulmonary veins, center of posterior left atrial wall, terminal crest, and Bachmann's bundle. Histology sections were assessed for extent of fibrosis, fatty tissues, and inflammatory infiltration at each location. No correlation was observed between age and fibrosis at any location. Fibrosis extent and fatty infiltration were twofold to threefold higher at all locations in patients with history of AF and correlated with lymphomononuclear infiltration. Patients with permanent AF had greater fibrosis extent than did patients with paroxysmal AF. In post-mortem material, structural changes in the atria were not associated with age, but were significantly correlated with presence of AF and its severity. Our findings suggest that age-related changes per se are unlikely to be the sole cause of advanced fibrosis underlying AF. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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              Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation.

              Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting, and traditional pharmacological approaches have proved to have important weaknesses. Structural remodeling has been observed in both clinical and experimental AF paradigms, and is an important feature of the AF substrate, producing fibrosis that alters atrial tissue composition and function. The precise mechanisms underlying atrial fibrosis are not fully elucidated, but recent experimental studies and clinical investigations have provided valuable insights. A variety of signaling systems, particularly involving angiotensin II and related mediators, seem to be centrally involved in the promotion of fibrosis. This paper reviews the current understanding of how atrial fibrosis creates a substrate for AF, summarizes what is known about the mechanisms underlying fibrosis and its progression, and highlights emerging therapeutic approaches aimed at attenuating structural remodeling to prevent AF.
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                Author and article information

                Contributors
                Journal
                EP Europace
                Oxford University Press (OUP)
                1099-5129
                1532-2092
                October 01 2021
                October 09 2021
                May 11 2021
                October 01 2021
                October 09 2021
                May 11 2021
                : 23
                : 10
                : 1559-1567
                Affiliations
                [1 ]Unitat de Fibril.lació Auricular (UFA), Institut Clínic Cardiovascular (ICCV), Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain
                [2 ]Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBABS), Barcelona, Catalonia, Spain
                [3 ]Department of Cardiology and Angiology, Charité—University Medicine Berlin, Charité Campus Mitte, Berlin, Germany
                [4 ]DZHK (German Centre for Cardiovascular Research), Berlin, Germany
                [5 ]Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
                [6 ]Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain
                Article
                10.1093/europace/euab107
                33975341
                b00a7758-7568-4ffd-af8e-93b1332e40fa
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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