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

Junaid A.B Zaman,Leanne Harling,Hutan Ashrafian,Ara Darzi,Nigel Gooderham,Thanos Athanasiou,Nicholas S Peters

doi:10.1016/j.ijcard.2016.06.249

Junaid A.B Zaman, Leanne Harling + Show 5 more

Open Access

https://doi.org/10.1016/j.ijcard.2016.06.249

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Abstract

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 200/500/1000ms cycle lengths (CL) was performed, recording episodes of AF>30s. Co-localised RA tissue was snap frozen for RNA and protein extraction. ResultsElectrograms prolonged during AF (76.64±29.35ms) vs. NSR/pacing (p<0.001). Compared to NSR, electrogram amplitude was reduced during AF and during pacing at 200ms CL (p<0.001). Electrogram DF was significantly lower in AF (75.87±23.63Hz) vs. NSR (89.33±25.99Hz) (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.

Highlights

Post-operative atrial fibrillation (POAF) is a major health economic burden
This study is the first to identify that intraoperative electrograms obtained during sinus rhythm in patients with no prior history of Atrial fibrillation (AF) have a higher dominant frequency (DF) than those obtained during AF
Whilst this is compatible with the ‘AF nest’ theory, whereby sources in the atrium harbouring AF are detectable at baseline in patients undergoing AF ablation, these findings are the first in such an upstream, unremodelled cohort [8]

Summary

Introduction

Post-operative atrial fibrillation (POAF) is a major health economic burden. the precise mechanisms in POAF remain unclear. 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. De novo post-operative atrial fibrillation (POAF) affects approximately 30–60% of patients undergoing cardiac surgery [1,2]. The make-up or existence of any predisposing atrial substrate for POAF remains poorly understood

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