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Post-operative atrial fibrillation is associated with a pre-existing structural and electrical substrate in human right atrial myocardium

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Title: Post-operative atrial fibrillation is associated with a pre-existing structural and electrical substrate in human right atrial myocardium
Authors: Zaman, J
Harling, L
Ashrafian, H
Darzi, A
Gooderham, N
Athanasiou, T
Peters, N
Item Type: Journal Article
Abstract: © 2016 The AuthorsBackground Post-operative atrial fibrillation (POAF) is a major health economic burden. However, the precise mechanisms in POAF remain unclear. In other forms of AF, sites of high dominant frequency (DF) in sinus rhythm (SR) may harbour ‘AF nests’. We studied AF inducibility in relation to substrate changes using epicardial electrograms and cardiomyocyte calcium handling in the atria of AF naïve patients. Method Bipolar electrograms were recorded from the lateral right atrial (RA) wall in 34 patients undergoing coronary surgery using a high-density array in sinus rhythm (NSR). RA burst pacing at 200/500/1000 ms cycle lengths (CL) was performed, recording episodes of AF > 30 s. Co-localised RA tissue was snap frozen for RNA and protein extraction. Results Electrograms prolonged during AF (76.64 ± 29.35 ms) vs. NSR/pacing (p < 0.001). Compared to NSR, electrogram amplitude was reduced during AF and during pacing at 200 ms CL (p < 0.001). Electrogram DF was significantly lower in AF (75.87 ± 23.63 Hz) vs. NSR (89.33 ± 25.99 Hz) (p < 0.05), and NSR DF higher in AF inducible patients at the site of AF initiation (p < 0.05). Structurally, POAF atrial myocardium demonstrated reduced sarcolipin gene (p = 0.0080) and protein (p = 0.0242) expression vs. NSR. Phospholamban gene and protein expression was unchanged. SERCA2a protein expression remained unchanged, but MYH6 (p = 0.0297) and SERCA2A (p = 0.0343) gene expression was reduced in POAF. Conclusions Human atrial electrograms prolong and reduce in amplitude in induced peri-operative AF vs. NSR or pacing. In those sustaining AF, high DF sites in NSR may indicate ‘AF nests’. This electrical remodelling is accompanied by structural remodelling with altered expression of cardiomyocyte calcium handling detectable before POAF. These novel upstream substrate changes offer a novel mechanism and manifestation of human POAF.
Issue Date: 28-Jun-2016
Date of Acceptance: 28-Jun-2016
URI: http://hdl.handle.net/10044/1/34178
DOI: http://dx.doi.org/10.1016/j.ijcard.2016.06.249
ISSN: 1874-1754
Publisher: Elsevier
Start Page: 580
End Page: 588
Journal / Book Title: International Journal of Cardiology
Volume: 220
Copyright Statement: © 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare Charity
Wellcome Trust
British Heart Foundation
Funder's Grant Number: RD410
Keywords: Atrial Fibrillation
Coronary artery bypass grafting
1102 Cardiovascular Medicine And Haematology
Publication Status: Published
Appears in Collections:Department of Surgery and Cancer
Institute of Global Health Innovation