Background: Treatment of atrial fibrillation (AF) in horses is challenged by high recurrence rates, potentially driven by underlying myocardial changes or remodelling caused by AF itself. Understanding the molecular mechanisms behind these changes is crucial for developing new targeted therapies and improving treatment outcomes. Objectives: To characterize the cardiac transcriptome of healthy horses and explore the transcriptional changes associated with persistent AF. Study design: Case-control study. Methods: RNA-sequencing was performed on samples from all four heart chambers collected from six horses with naturally occurring persistent AF (lasting 2–12 weeks) and six healthy controls. Differential gene expression and pathway enrichment analyses were conducted to identify chamber specific differences and molecular pathways associated with AF. Findings were integrated with proteomic data and compared to transcriptional changes observed in tachypacing-induced AF. Atrial metabolic remodelling was further investigated by evaluating AMP-activated protein kinase (AMPK) activity and local glycogen content. Results: The transcriptomes of the four heart chambers had distinct molecular identities. Expression of ion channels and genes encoding calcium handling proteins were largely similar to humans, despite important differences in the ventricular expression of repolarizing potassium channels. Persistent AF was associated with minimal ion channel changes but significant upregulation of metabolic, fibrotic, and myofibrillar pathways. Metabolic remodelling included transcriptional upregulation of glycolytic pathways, increased glycogen content in the left atrium, and preserved AMPK activity in the right atrium. The transcriptomic profiles of persistent AF correlated well with those of tachypacing-induced AF. Main limitations: The study cannot distinguish changes predisposing to AF from those caused by it. Functional validation of ion channel currents was not performed. Conclusion: Persistent AF was associated with changes in metabolic and fibrotic pathways in the atria, with minimal ion channel remodelling. Targeting these pathways, rather than focusing solely on the electrical disturbance, may improve treatment outcomes in equine AF.

Abstract Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia following coronary artery bypass grafting (CABG). We hypothesized that measures of left atrial (LA) function would be useful in predicting AF in patients undergoing CABG. Methods and Results In the study, 611 patients were included after CABG. All patients had echocardiograms performed preoperatively and LA functional measurements were assessed. These measurements were LA maximum volume index (LAVmax), LA minimum volume index (LAVmin) and LA emptying fraction (LAEF). The endpoint was AF occurring >14 days after surgery. During the follow-up period of a median of 3.7 years, 52 (9%) developed AF. The mean age was 67 years, 84% were male and the average left ventricle ejection fraction was 50 %. No differences were observed between the patients developing AF and those who did not develop AF. No functional LA measurements were significant predictors of AF in the whole CABG population. However, in patients with normal-sized LA (n=532, events: 49), both LAEF and LAVmin were univariable predictors of AF. When the functional measurements were adjusted for the CHADS 2 score, both LAVmin (HR=1.07 (1.01-1.13), p=0.014 ) and LAEF (HR: 1.02 (1.00-1.03, p= 0.023)), remained significant predictors. Conclusion No echocardiographic measurements were significant predictors of AF after CABG. In patients with a normal LA size, LAVmin as well as LAEF were significant predictors of AF. Keywords: atrial fibrillation; cardiac surgery; left atrium; echocardiography