title: Patient-derived models link re-entrant driver localization in atrial fibrillation to fibrosis spatial pattern.
abstract: The mechanisms underlying persistent atrial fibrillation (AF) in patients with atrial fibrosis are poorly understood. The goal of this study was to use patient-derived atrial models to test the hypothesis that AF re-entrant drivers (RDs) persist only in regions with specific fibrosis patterns.
  
  
  
  Twenty patients with persistent AF (PsAF) underwent late gadolinium-enhanced MRI to detect the presence of atrial fibrosis. Segmented images were used to construct personalized 3D models of the fibrotic atria with biophysically realistic atrial electrophysiology. In each model, rapid pacing was applied to induce AF. AF dynamics were analysed and RDs were identified using phase mapping. Fibrosis patterns in RD regions were characterized by computing maps of fibrosis density (FD) and entropy (FE). AF was inducible in 13/20 models and perpetuated by few RDs (2.7 ± 1.5) that were spatially confined (trajectory of phase singularities: 7.6 ± 2.3 mm). Compared with the remaining atrial tissue, regions where RDs persisted had higher FE (IQR: 0.42-0.60 vs. 0.00-0.40, P < 0.05) and FD (IQR: 0.59-0.77 vs. 0.00-0.33, P < 0.05). Machine learning classified RD and non-RD regions based on FD and FE and identified a subset of fibrotic boundary zones present in 13.8 ± 4.9% of atrial tissue where 83.5 ± 2.4% of all RD phase singularities were located.
  
  
  
  Patient-derived models demonstrate that AF in fibrotic substrates is perpetuated by RDs persisting in fibrosis boundary zones characterized by specific regional fibrosis metrics (high FE and FD). These results provide new insights into the mechanisms that sustain PsAF and could pave the way for personalized, MRI-based management of PsAF.
authors.affiliation: Institute for Computational Medicine, Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Sohail
authors.initials: S
authors.lastname: Zahid
authors.affiliation: IHU LIRYC, Electrophysiology and Heart Modeling Institute, INSERM U1045, Bordeaux, France Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Cochet
authors.affiliation: Institute for Computational Medicine, Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Boyle
authors.affiliation: Institute for Computational Medicine, Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Schwarz
authors.affiliation: Institute for Computational Medicine, Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Kaitlyn N
authors.initials: KN
authors.lastname: Whyte
authors.affiliation: IHU LIRYC, Electrophysiology and Heart Modeling Institute, INSERM U1045, Bordeaux, France.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Vigmond
authors.affiliation: IHU LIRYC, Electrophysiology and Heart Modeling Institute, INSERM U1045, Bordeaux, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Dubois
authors.affiliation: IHU LIRYC, Electrophysiology and Heart Modeling Institute, INSERM U1045, Bordeaux, France Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Mélèze
authors.initials: M
authors.lastname: Hocini
authors.affiliation: IHU LIRYC, Electrophysiology and Heart Modeling Institute, INSERM U1045, Bordeaux, France Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Haïssaguerre
authors.affiliation: IHU LIRYC, Electrophysiology and Heart Modeling Institute, INSERM U1045, Bordeaux, France Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Jaïs
authors.affiliation: Institute for Computational Medicine, Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA ntrayanova@jhu.edu.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Trayanova
mesh_terms: D000200:Action Potentials; D000328:Adult; D001281:Atrial Fibrillation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D064752:Atrial Remodeling; D002304:Cardiac Pacing, Artificial; D055424:Cardiac-Gated Imaging Techniques; D003198:Computer Simulation; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D005355:Fibrosis; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular
keywords: Computational modelling; Fibrosis; Patient-derived atrial models; Persistent atrial fibrillation; Re-entrant drivers