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Background: Left atrial structural remodelling, assessed by left atrial (LA) sphericity or antero-posterior diameter, has been shown to predict recurrence after atrial fibrillation (AF) ablation. The study aimed to perform a computational shape analysis of the LA to quantitatively characterise the LA shape remodelling process and identify metrics that optimally predict recurrence. Methods: Pre-procedural bright-blood MRIs of the LA of patients undergoing AF ablation were segmented. Patient-specific smooth 3D meshes were fitted to the segmentations. A statistical shape model of the LA was created and the global features underpinning the observed shape variation extracted as principal components (PCs). PCs were optimally combined to create non-empirical atlas-based metrics using linear discriminant analysis. Meshes depicting mean and extreme recurrent and non-recurrent LA shapes were also synthetized. The capability of different metrics to predict recurrence was evaluated using the area under the ROC curve (AUC) of a leave 1 out cross validation test. Results: In total, 111 patients were included. At 12 months follow-up, LA sphericity was the best predictor of recurrence (AUC: 0.66) over novel atlas-based metrics (AUC: 0.65). At 24 months, atlas-based metrics were the best predictors of recurrence (AUC: 0.66), outperforming a combination of sphericity and volume (AUC: 0.64), sphericity alone (AUC: 0.63) and any other traditional metric. Conclusions: Novel atlas-based metrics improve the prediction of recurrence at 2 years post-AF ablation. They allow a more complete characterization of the LA shape remodelling process, for example by allowing the synthesis of recurrent and non-recurrent LA shapes, which may contribute to patient stratification for AF ablation.

Sheep are often used as animal models for experimental studies into the underlying mechanisms of cardiac arrhythmias. Previous studies have shown that biophysically detailed computer models of the heart provide a powerful alternative to experimental animal models for underpinning such mechanisms. In this study, we have developed a family of mathematical models for the electrical action potentials of various sheep atrial cell types. The developed cell models were then incorporated into a three-dimensional anatomical model of the sheep atria, which was recently reconstructed and segmented based on anatomical features within different regions. This created a novel biophysically detailed computational model of the three-dimensional sheep atria. Using the model, we then investigated the mechanisms by which paroxysmal rapid focal activity in the pulmonary veins can transit to sustained atrial fibrillation. It was found that the anisotropic property of the atria arising from the fibre structure plays an important role in facilitating the development of fibrillatory atrial excitation waves, and the electrical heterogeneity plays an important role in its initiation.

Transmural gradients in myocyte action potential duration (APD) and Ca(2+)-handling proteins are argued to be important for both the normal functioning of the ventricle and arrhythmogenesis. In rabbit, the transmural gradient in APD (left ventricular wedge preparation) is minimal in the neonate. During postnatal development, APD increases both in the epicardium and the endocardium, but the prolongation is more substantial in the endocardium leading to a significant transmural gradient. We have investigated changes in the expression of ion channels and also Ca(2+)-handling proteins in the subepicardial and subendocardial layers of the left ventricular free wall in neonatal (2-7 days of age) and adult male (~6 months of age) New Zealand White rabbits using quantitative PCR and also, when possible, in situ hybridisation and immunohistochemistry. In the adult, there were significant and substantial transmural gradients in Ca(v)1.2, KChIP2, ERG, K(v)LQT1, K(ir)2.1, NCX1, SERCA2a and RyR2 at the mRNA and, in some cases, protein level-in every case the mRNA or protein was more abundant in the epicardium than the endocardium. Of the eight transmural gradients seen in the adult, only three were observed in the neonate and, in two of these cases, the gradients were smaller than those in the adult. However, in the neonate there were also transmural gradients not observed in the adult: in HCN4, Na(v)1.5, minK, K(ir)3.1 and Cx40 mRNAs - in every case the mRNA was more abundant in the endocardium than the epicardium. If the postnatal changes in ion channel mRNAs are used to predict changes in ionic conductances, mathematical modelling predicts the changes in APD observed experimentally. It is concluded that many of the well known transmural gradients in the ventricle develop postnatally.