Heterogeneous atrial wall thickness and stretch promote scroll waves anchoring during atrial fibrillation.
OBJECTIVE
Atrial dilatation and myocardial stretch are strongly associated with atrial fibrillation (AF). However, the mechanisms by which the three-dimensional (3D) atrial architecture and heterogeneous stretch contribute to AF perpetuation are incompletely understood. We compared AF dynamics during stretch-related AF (pressure: 12 cmH(2)O) in normal sheep hearts (n = 5) and in persistent AF (PtAF, n = 8)-remodelled hearts subjected to prolonged atrial tachypacing. We hypothesized that, in the presence of stretch, meandering 3D atrial scroll waves (ASWs) anchor in regions of large spatial gradients in wall thickness.


RESULTS
We implemented a high-resolution optical mapping set-up that enabled simultaneous epicardial- and endoscopy-guided endocardial recordings of the intact atria in Langendorff-perfused normal and PtAF (AF duration: 21.3 ± 11.9 days) hearts. The numbers and lifespan of long-lasting ASWs (>3 rotations) were greater in PtAF than normal (lifespan 0.9 ± 0.5 vs. 0.4 ± 0.2 s/(3 s of AF), P< 0.05). Than normal hearts, focal breakthroughs interacted with ASWs at the posterior left atrium and left atrial appendage to maintain AF. In PtAF hearts, ASW filaments seemed to span the atrial wall from endocardium to epicardium. Numerical simulations using 3D atrial geometries (Courtemanche-Ramirez-Nattel human atrial model) predicted that, similar to experiments, filaments of meandering ASWs stabilized at locations with large gradients in myocardial thickness. Moreover, simulations predicted that ionic remodelling and heterogeneous distribution of stretch-activated channel conductances contributed to filament stabilization.


CONCLUSIONS
The heterogeneous atrial wall thickness and atrial stretch, together with ionic and anatomic remodelling caused by AF, are the main factors allowing ASW and AF maintenance.
Center for Arrhythmia Research, Department of Internal Medicine,  University of Michigan, 5025 Venture Drive, Ann Arbor, MI 48108,  USA.
Masatoshi
M
Yamazaki
Sergey
S
Mironov
Clément
C
Taravant
Julien
J
Brec
Luis M
LM
Vaquero
Krishna
K
Bandaru
Uma Mahesh R
UM
Avula
Haruo
H
Honjo
Itsuo
I
Kodama
Omer
O
Berenfeld
Jérôme
J
Kalifa
D000200:Action Potentials; D000818:Animals; D020517:Atrial Appendage / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016275:Atrial Function; D002304:Cardiac Pacing, Artificial; D003198:Computer Simulation; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D004724:Endoscopy; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008465:Mechanoreceptors / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D008955:Models, Cardiovascular; D009716:Numerical Analysis, Computer-Assisted; D010477:Perfusion; D011312:Pressure; D012756:Sheep; D013997:Time Factors; D056969:Voltage-Sensitive Dye Imaging