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2016 ; 110
(3
): 443-54
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Patient-derived models link re-entrant driver localization in atrial fibrillation
to fibrosis spatial pattern
#MMPMID27056895
Zahid S
; Cochet H
; Boyle PM
; Schwarz EL
; Whyte KN
; Vigmond EJ
; Dubois R
; Hocini M
; Haïssaguerre M
; Jaïs P
; Trayanova NA
Cardiovasc Res
2016[Jun]; 110
(3
): 443-54
PMID27056895
show ga
AIMS: 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. METHODS AND
RESULTS: 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. CONCLUSION: 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.