Published online before print August 17, 2007, doi: 10.1161/CIRCRESAHA.107.153858
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Submitted on April 10, 2007
Revised on July 27, 2007
Accepted on August 8, 2007
The Spatial Distribution of Fibrosis Governs Fibrillation Wave Dynamics in the Posterior Left Atrium During Heart Failure
Kazuhiko Tanaka ;
From the Institute for Cardiovascular Research, Department of Pharmacology (K.T., S.Z., K.L.V., M.Y., J.M., M.K., A.V.Z., R.V., D.S.A., S.L., J.J., O.B., J.K.), SUNY Upstate Medical University, Syracuse, NY; and Canadian Surgery Technologies and Advanced Robotics (G.G.), University of Western Ontario, London, Ontario, Canada.
* To whom correspondence should be addressed. E-mail: berenfeo{at}upstate.edu.
Heart failure (HF) commonly results in atrial fibrillation (AF) and fibrosis, but how the distribution of fibrosis impacts AF dynamics has not been studied. HF was induced in sheep by ventricular tachypacing (220 bpm, 6 to 7 weeks). Optical mapping (Di-4-ANEPPS, 300 frames/sec) of the posterior left atrial (PLA) endocardium was performed during sustained AF (burst pacing) in Langendorff-perfused HF (n=7, 4 µmol/L acetylcholine; n=3, no acetylcholine) and control (n=6) hearts. PLA breakthroughs were the most frequent activation pattern in both groups (72.0±4.6 and 90.2±2.7%, HF and control, respectively). However, unlike control, HF breakthroughs preferentially occurred at the PLAs periphery near the pulmonary vein ostia, and their beat-to-beat variability was greater than control (1.93±0.14 versus 1.47±0.07 changes/[beats/sec], respectively, P<0.05). On histological analysis (picrosirius red), the area of diffuse fibrosis was larger in HF (23.4±0.4%) than control (14.1±0.6%; P<0.001, n=4). Also the number and size of fibrous patches were significantly larger and their location was more peripheral in HF than control. Computer simulations using 2-dimensional human atrial models with structural and ionic remodeling as in HF demonstrated that changes in AF activation frequency and dynamics were controlled by the interaction of electrical waves with clusters of fibrotic patches of various sizes and individual pulmonary vein ostia. During AF in failing hearts, heterogeneous spatial distribution of fibrosis at the PLA governs AF dynamics and fractionation.
Key words: heart failure • atrial fibrillation • fibrosis • mapping • numerical simulations
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