The contact electrogram and its architectural determinants in atrial fibrillation

Abstract

BackgroundThe basis for the contact electrogram, the basic unit of cardiac electrophysiology, is only partly understood, especially in atrial fibrillation, the commonest sustained cardiac arrhythmia. We aimed to characterise the determinants of electrogram formation by electrophysiological investigation and by tissue level substrate characterisation in human and rat atrial tachycardia (AT) and atrial fibrillation (AF) using high density epicardial electrode arrays. MethodsHuman intraoperative epicardial pacing was performed in nine patients from the right atrial wall using a high density AFocusII 20 electrode catheter at 500 ms and 200ms cycle lengths to assess AF inducibility. None of the patients had had atrial fibrillation and were operated on using cardiopulmonary bypass. Burst pacing was conducted and resulting electrograms recorded using BARD software in real time. Ten brown Norway rats and ten spontaneous hypertensive rats were culled at 12–14 weeks of age and hearts removed rapidly for ex-vivo Langendorff experiments. Bilateral epicardial atrial appendage electrograms were recorded with a high-density microelectrode array consisting of 32 50 μm electrodes at 300 μm spacing. 10 s burst pacing was performed from the right atrium using decreasing cycle lengths from 150 ms to 30 ms and atrial arrhythmia susceptibility, electrogram duration, and interatrial conduction time measured. Ventricular programmed electrical stimulation with an S1-S2 protocol was performed before tissue was frozen for histological analysis. FindingsHuman bipolar electrograms recorded intraoperatively were significantly prolonged with shortened cycle lengths of pacing but were no different between those who developed AF for more than 30 s (n=6) and those who did not (n=3). Rat atrial electrogram duration was no different between groups during intrinsic rhythm but mean conduction velocity was statistically significantly different between both species and right and left atrial appendages, as was interatrial conduction time. Brown Norway rats were significantly more likely to have a 30 s episode of AT or AF recorded than were spontaneous hypertensive rats, but no difference was seen in ventricular arrhythmias. The heart weight:body weight ratio confirmed that spontaneous hypertensive rats had cardiac sequelae of hypertension. InterpretationLocal electrogram prolongation is witnessed in human AF, and AF induction using a standard pacing protocol confirmed those capable of developing arrhythmia. There is an overt electrophysiological phenotype of AF susceptibility in brown Norway rats compared with spontaneous hypertensive rats, which is unaccompanied by underlying changes in mean electrogram duration. Further work is required to investigate the underlying substrate for these findings, especially with respect to electrogram determination and formation. FundingBritish Heart Foundation.