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Original Investigation |

Association of Atrial Tissue Fibrosis Identified by Delayed Enhancement MRI and Atrial Fibrillation Catheter Ablation:  The DECAAF Study

Nassir F. Marrouche, MD1; David Wilber, MD2; Gerhard Hindricks, MD3; Pierre Jais, MD4; Nazem Akoum, MD1; Francis Marchlinski, MD5; Eugene Kholmovski, PhD1; Nathan Burgon, BSc1; Nan Hu, PhD1; Lluis Mont, MD6; Thomas Deneke, MD7; Mattias Duytschaever, MD8; Thomas Neumann, MD9; Moussa Mansour, MD10; Christian Mahnkopf, MD11; Bengt Herweg, MD12; Emile Daoud, MD13; Erik Wissner, MD14; Paul Bansmann, MD15; Johannes Brachmann, MD11
[+] Author Affiliations
1Comprehensive Arrhythmia and Research Management Center, University of Utah School of Medicine, Salt Lake City
2Loyola University Medical Center, Maywood, Illinois
3University of Leipzig, Leipzig, Germany
4Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
5Hospital of the University of Pennsylvania, Philadelphia
6University of Barcelona, Barcelona, Spain
7BG-Kliniken Bergmannsheil, University of Bochum, Bochum, Germany
8University Hospital Ghent, Ghent, Belgium
9Kerckhoff Heart Center, Bad Nauheim, Germany
10Massachusetts General Hospital, Boston
11Klinikum Coburg GmbH, II, Medizinische Klinik, Coburg, Germany
12Morsani College of Medicine, University of South Florida, Tampa
13Ohio State University, Columbus
14Asklepios Klinik St Georg, Hamburg, Germany
15Medical Center Porz am Rhein, Cologne, Germany
JAMA. 2014;311(5):498-506. doi:10.1001/jama.2014.3.
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Published online

Importance  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.

Objective  To characterize the feasibility of atrial tissue fibrosis estimation by delayed enhancement MRI and its association with subsequent AF ablation outcome.

Design, Setting, and Participants  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.

Main Outcomes and Measures  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).

Results  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).

Conclusions and Relevance  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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Figure 1.
Process for Quantification of Left Atrial Wall Fibrosis

High-resolution 3D delayed enhancement magnetic resonance imaging (MRI) scans of the left atrium are acquired (step 1). Epicardial and endocardial borders are contoured in each MRI slice to define the left atrial wall segmented region (step 2). Wall segmentations include the 3D extent of both the left atrial wall and the antral regions of the pulmonary veins, but exclude the mitral valve. Quantification of fibrosis is based on relative intensity of contrast enhancement (step 3). The 3D model of the left atrium is rendered from the endocardial (left atrial cavity) and left atrial wall segmentations, and the maximum enhancement intensities are projected on the surface of the model (step 4). Interactive 3D model.

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Figure 2.
Four Stages of Left Atrial Tissue Fibrosis Based on 3D Delayed Enhancement Magnetic Resonance Imaging Scans

Representative example from 4 different patients of each stage of left atrial tissue fibrosis. Normal left atrial wall is displayed in blue; fibrotic changes are in green and white. Stages 1 through 4 show increasing amounts of fibrosis as a percentage of the total left atrial wall volume. The pulmonary veins and mitral valve are shown in gray.

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Figure 3.
Relationship of Atrial Fibrillation Recurrence With Percent Fibrosis

Adjusted for age, sex, hypertension, congestive heart failure, mitral valve disease, diabetes, atrial fibrillation type (paroxysmal or persistent), left atrial volume, left ventricular ejection fraction, and participating center (model 5) based on a cubic spline analysis with follow-up censored at day 325 after the blanking period. The strength of the association was greater at lower levels of fibrosis than at higher levels (P = .03 for test of nonlinearity). Blue dashed lines indicate 95% CI.

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Figure 4.
Cumulative Incidence of Arrhythmia Recurrence Without Covariate Adjustment Through Day 475 After the Blanking Period

Small vertical ticks on curves indicate where a patient’s follow-up has completed without recurrent atrial fibrillation.

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