Imperial College London
Alternate

Emeritus ProfessorNigelGooderham

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Emeritus Professor of Molecular Toxicology
 
 
 
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Contact

 

n.gooderham Website

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zaman:2016:10.1016/j.ijcard.2016.06.249,
author = {Zaman, J and Harling, L and Ashrafian, H and Darzi, A and Gooderham, N and Athanasiou, T and Peters, N},
doi = {10.1016/j.ijcard.2016.06.249},
journal = {International Journal of Cardiology},
pages = {580--588},
title = {Post-operative atrial fibrillation is associated with a pre-existing structural and electrical substrate in human right atrial myocardium},
url = {http://dx.doi.org/10.1016/j.ijcard.2016.06.249},
volume = {220},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundPost-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.MethodBipolar 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.ResultsElectrograms 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.ConclusionsHuman 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.
AU  - Zaman,J
AU  - Harling,L
AU  - Ashrafian,H
AU  - Darzi,A
AU  - Gooderham,N
AU  - Athanasiou,T
AU  - Peters,N
DO  - 10.1016/j.ijcard.2016.06.249
EP  - 588
PY  - 2016///
SN  - 1874-1754
SP  - 580
TI  - Post-operative atrial fibrillation is associated with a pre-existing structural and electrical substrate in human right atrial myocardium
T2  - International Journal of Cardiology
UR  - http://dx.doi.org/10.1016/j.ijcard.2016.06.249
UR  - http://hdl.handle.net/10044/1/34178
VL  - 220
ER  -
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